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Background: Sunitinib, a multitarget tyrosine kinase inhibitor, showed encouraging antitumor activity and manageable toxicity in patients with advanced midgut neuroendocrine tumors (NETs) in earlier results from phase I and II trials., Patients and Methods: In this phase II trial, patients with a nonresectable grade 1 or 2 midgut progressive NET and Eastern Cooperative Oncology Group performance status 0-1 were randomly assigned 1:1 to receive 37.5 mg sunitinib or a placebo, combined with 120 mg lanreotide autogel every 28 days. The planned sample size was 104 patients. The primary outcome was investigator-assessed progression-free survival (PFS)., Results: The study was stopped early because of insufficient patient recruitment. Between January 2013 and December 2016, 44 patients were enrolled and received sunitinib ( n  = 22) or placebo ( n  = 22). The median age was 63.7 years ( Q 1- Q 3 range, 56.6-68.1) and 26 patients (59.1%) were male. The main localization was ileum ( N  = 37, 84.1%) and the majority were grade 2 ( n  = 25, 56.8%). The median follow-up was 36.7 months (95% confidence interval (CI) 34.6-48.2). The median PFS was 9.84 months (95% CI 6.8-23.3) with sunitinib and 11.47 months (95% CI 5.4-15.3) with placebo (hazard ratio (HR) = 0.80, 95% CI 0.41-1.56, p  = 0.51). There was no difference in overall survival between treatment arms (HR = 0.81, (95% CI 0.32-2.01), p  = 0.64). The objective response rate was 9.1% with sunitinib and 0.0% with placebo, and 19 patients (86.4%) had stable disease. Thirty-nine patients (88.6%) completed the baseline QLQ-C30 questionnaire. Baseline health-related quality of life level was similar between treatment arms, except for physical and emotional functioning which were higher ( p  = 0.089) and lower ( p  = 0.023) in the sunitinib arm, respectively. Trends toward longer time until a definitive deterioration in favor of the sunitinib arm were observed for 10 out of 15 dimensions (HRs < 1), with a significant result for financial difficulties (HR = 0.31, (90% CI 0.10-0.94)). Twenty-seven patients (61.4%) had at least one adverse event grade ⩾3 (sunitinib: 72.7%, placebo: 50.0%), with only one patient grade 4 for hypertension and vomiting. Eleven deaths non-related to treatment occurred (sunitinib arm: n  = 5, placebo arm: n  = 6)., Conclusion: Our study does not provide enough evidence to conclude the role of sunitinib in advanced midgut NETs, primarily due to a lower-than-expected number of enrolled patients. While we cannot entirely rule out the efficacy of sunitinib, lanreotide alone may play a significant role., Trial Registration: EudraCT: 2012-001098-94., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Background: Ebola (EBOV) and Sudan (SUDV) orthoebolaviruses are responsible for lethal hemorrhagic fever outbreaks in humans in Central and West Africa, and in apes that can be at the source of human outbreaks for EBOV., Methods: To assess the risk of exposure to orthoebolaviruses through contact with nonhuman primates (NHP), we tested the presence of antibodies against different viral proteins with a microsphere-based multiplex immunoassay in a case-control study on bites from NHPs in forest areas from Cameroon (n = 795) and in cross-sectional surveys from other rural populations (n = 622) of the same country., Results: Seroreactivities against at least 2 viral proteins were detected in 13% and 12% of the samples for EBOV and SUDV, respectively. Probability of seroreactivity was not associated with history of NHP bites, but was 3 times higher in Pygmies compared to Bantus. Although no neutralizing antibodies to EBOV and SUDV were detected in a selected series of highly reactive samples, avidity results indicate strong affinity to SUDV antigens., Conclusions: The detection of high level of seroreactivities against orthoebolaviruses in rural Cameroon, where no outbreaks have been reported, raises the possibilities of silent circulation of orthoebolaviruses, or of other not yet documented filoviruses, in these forested regions., Article's Main Point: Our study found high seroreactivities to Ebola and Sudan orthoebolavirus antigens in rural Cameroonian populations, especially among Pygmies, despite no reported outbreaks. This suggests potential silent circulation of orthoebolaviruses or unknown filoviruses, highlighting the need for further surveillance and research., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background and Objectives: Data on HIV drug resistance in Madagascar are rare and outdated. In this study, we assessed the prevalence of HIV drug resistance mutations to antiretrovirals (ARVs) and genetic diversity of circulating strains in treatment-naive people living with HIV (PLHIV) in Madagascar., Materials and Methods: We amplified the protease (PR), fragments of the Reverse Transcriptase (RT) and Integrase (IN) genes according to the French ANRS protocol. The amplicons were sequenced using next-generation sequencing technology on an Illumina platform (MiSeq). We determined HIV-1 subtypes through phylogenetic analysis using maximum likelihood in PhyML. Resistance interpretation was performed using the Stanford algorithm (version 9.5.1)., Results: We included 239 HIV-infected adults and children, sampled between January 2019 and November 2023, with a median age of 30 years and a mean plasma HIV viral load of 6.3 Log copies/mL. We sequenced at least one genomic fragment (PR or RT or IN) of the 239 samples, but 9 were excluded from analysis (mean depth < 10,000×). Phylogenetic analysis of 230 sequences revealed the presence of subtype C (33.91 %), A1 (11.30 %), B (11.30 %), CRF02&#95;AG (9.56 %), subtype G (3.04 %), subtype D (0.43 %), CRF01&#95;AE (0.43 %), and a significant proportion of unique recombinant forms (URFs) (30.30 %). The prevalence of transmitted drug resistance (TDR) was 4.95 % (10/202) among patients aged 15 years and older. When stratified by ARV class, this prevalence was 4.79 % for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 0.59 % for Nucleoside Reverse Transcriptase inhibitors (NRTIs), and 0.50 % for integrase strand transfer inhibitors (INSTIs). Among children under 15 years old (n = 28), the prevalence of TDR was 14.28 % (4/28), with all mutations conferring resistance to NNRTIs. No mutation conferring resistance to protease inhibitors was found, neither in children nor in adults., Conclusion: Our results show a low prevalence of ARV resistance mutations among adult treatment-naive PLHIV in Madagascar. In children under 15 years old, 92 % were infants under two years old, the high resistance rate is likely related to mother-to-child transmission. No resistance mutation to dolutegravir was detected. We also observed high frequencies of subtypes C, B, A1 and a high proportion of URFs, highlighting an ongoing dynamic epidemic., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Dengue is a widespread viral infection transmitted from mosquitoes to humans, mainly in tropical and subtropical climates. In Benin, only dengue virus (DENV) serotype 2 infection has been previously described in humans. This study aimed to investigate DENV infection and serotypes in suspected patients., Methods: Plasma samples from 464 patients attending health centers in February 2023 with clinical symptoms and suspected for dengue infection were included, and analyzed for DENV by real time quantitative Polymerase Chain Reaction (Dengue Altona 3.0 kit). PCR positives samples were further characterized by whole genome sequencing and phylogenetic analysis to identify the circulating DENV serotype., Results: The RT-qPCR results showed that four patients (D6, D23, D28, D44) were positive with the cycle threshold values less than 40 (31.3, 34.7, 14.7 and 14.3) respectively. Full-length DENV sequences were obtained for D6, D28 and D44. One patient (D6) was infected with DENV-1 serotype, and the two others (D28 and D44) were positive for DENV-3. Phylogenetic analysis shows that the new DENV-1 sequence is close to those obtained in Burkina Faso in 2022 and Nigeria in 2023, and the two DENV-3 sequences form a separate cluster with sequences obtained in Burkina Faso in 2022., Conclusion: We showed for the first time, the presence of dengue serotype 1 and serotype 3 infection in Benin. These results send a strong signal to health authorities and show that arbovirus surveillance efforts must be integrated into pathogen monitoring programs., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The diagnosis of diabetes mellitus (DM) affecting 537 million adults worldwide relies on invasive and costly enzymatic methods that have limited stability. Electroactive polypyrrole (PPy)-based molecularly imprinted polymer nanoparticles (eMIPs) have been developed that rival the affinity of enzymes whilst being low-cost, highly robust, and facile to produce. By drop-casting eMIPs onto low-cost disposable screen-printed electrodes (SPEs), sensors have been manufactured that can electrochemically detect glucose in a wide dynamic range (1 µm-10 mm) with a limit of detection (LOD) of 26 nm. The eMIPs sensors exhibit no cross reactivity to similar compounds and negligible glucose binding to non-imprinted polymeric nanoparticles (eNIPs). Measurements of serum samples of diabetic patients demonstrate excellent correlation (>0.93) between these eMIPs sensor and the current gold standard Roche blood analyzer test. Finally, the eMIPs sensors are highly durable and reproducible (storage >12 months), showcasing excellent robustness and thermal and chemical stability. Proof-of-application is provided via measuring glucose using these eMIPs sensor in a two-electrode configuration in spiked artificial interstitial fluid (AISF), highlighting its potential for non-invasive wearable monitoring. Due to the versatility of the eMIPs that can be adapted to virtually any target, this platform technology holds high promise for sustainable healthcare applications via providing rapid detection, low-cost, and inherent robustness., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Introduction: The abscopal effect is a systemic immune response characterized by metastases regression at sites distant from the irradiated lesion. This systematic review aims to explore the immunological mechanisms of action underlying the abscopal effect and to investigate how hyperthermia (HT) can increase the chances of radiotherapy (RT) triggering systemic anti-tumor immune responses., Methods: This review is created in accordance with the PRISMA guidelines., Results and Conclusion: HT and RT have both complementary and synergistic immunological effects. Both methods trigger danger signal release, promoting cytokine and chemokine secretion, which increases T-cell infiltration and facilitates cell death. Both treatments upregulate extracellular tumor HSP70, which could amplify DAMP recognition by macrophages and DCs, leading to stronger tumor antigen presentation and CTL-mediated immune responses. Additionally, the combined increase in cell adhesion molecules (VCAM-1, ICAM-1, E-selectin, L-selectin) could enhance leukocyte adhesion to tumors, improving lymphocyte trafficking and boosting systemic anti-tumor effects. Lastly, HT causes vasodilation and improves blood flow, which might exacerbate those distant effects. We suggest the combination of local radiotherapy with fever-range whole-body hyperthermia to optimally enhance the chances of triggering the abscopal effect mediated by the immune system.

Recent reports raise concerns on the changing epidemiology of mpox in the Democratic Republic of the Congo (DRC). High-quality genomes were generated for 337 patients from 14/26 provinces to document whether the increase in number of cases is due to zoonotic spillover events or viral evolution, with enrichment of APOBEC3 mutations linked to human adaptation. Our study highlights two patterns of transmission contributing to the source of human cases. All new sequences from the eastern South Kivu province (n = 17; 4.8%) corresponded to the recently described clade Ib, associated with sexual contact and sustained human-to-human transmission. By contrast, all other genomes are clade Ia, which exhibits high genetic diversity with low numbers of APOBEC3 mutations compared with clade Ib, suggesting multiple zoonotic introductions. The presence of multiple clade I variants in urban areas highlights the need for coordinated international response efforts and more studies on the transmission and the reservoir of mpox., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Oligometastatic breast cancer (OMBC) is a clinical entity with a prospect of long-term survival, but uncertainty remains on its optimal treatment. We studied whether intensified alkylating chemotherapy (IACT) improves long-term outcome compared to conventional-dose chemotherapy (CDCT) as part of a multimodality approach for patients with OMBC harboring homologous recombination deficiency (HRD)., Patients and Methods: Eligible patients had HER2-negative OMBC, harboring HRD, with ≤ 3 distant metastases, pathologic proof of distant disease and a favorable response to three cycles CDCT. Participants were randomized 1:1 to continue with either CDCT or IACT. IACT consisted of one mobilization course followed by two cycles of mini-CTC (carboplatin, thiotepa and cyclophosphamide) supported by peripheral blood progenitor cell reinfusion. Primary outcome was event-free survival (EFS). Secondary endpoints included overall survival (OS), quality of life and safety., Results: Seventy-five patients were randomized to either IACT (n = 36) or CDCT (n = 39). Twenty-three (31 %) patients had hormone receptor-positive disease and 52 (69 %) had triple-negative disease. Median EFS in the IACT-group was 28 months (95 % confidence interval [CI] 21-not reached [NR]) versus 25 months (95 %CI 14-NR) in the CDCT-group (hazard ratio [HR] for recurrence or death 0.78, 95 %CI 0.42-1.42). Median OS was 67 months (95 %CI 37-NR) in the IACT-group and 36 (95 %CI 26-NR) in the CDCT-group (HR 0.74, 95 %CI 0.37-1.48)., Conclusions: The entire study population experienced long-term survival, with median OS well over five years. IACT compared to CDCT did not improve outcome in patients with OMBC harboring study-defined HRD. The optimal therapy for patients with OMBC requires further study., Trial Registration: ClinicalTrials.gov: NCT01646034., Competing Interests: Declaration of Competing Interest TS reports the receipt of honoraria from Gilead Sciences outside the submitted work. SL reports grants from ZonMw and A Sister’s Hope; has been an advisory board member for AstraZeneca, Cergentis, IBM, Novartis, Pfizer, Sanofi and Roche; and received institutional research grants from Agendia, AstraZeneca, Eurocept-pharmaceuticals and Merck and Pfizer. In addition, SL received institutional research grants and institutional non-financial support from Agendia, Genentech, Novartis, Roche, Tesaro and Immunomedics and other institutional support from AstraZeneca, Pfizer, Cergentis, Daiichi Sankyo, IBM and Bayer outside the submitted work. GS reports institutional research support from Agendia, AstraZeneca, Merck, Novartis, Roche and Seagen and consultancy for Biovica, Novartis, and Seagen. All remaining authors have declared no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: During the 2018-20 Ebola virus disease outbreak in the Democratic Republic of the Congo, thousands of patients received unprecedented vaccination, monoclonal antibody (mAb) therapy, or both, leading to a large number of survivors. We aimed to report the clinical, virological, viral genomic, and immunological features of two previously vaccinated and mAb-treated survivors of Ebola virus disease in the Democratic Republic of the Congo who developed second episodes of disease months after initial discharge, ultimately complicated by fatal meningoencephalitis associated with viral persistence., Methods: In this case report study, we describe the presentation, management, and subsequent investigations of two patients who developed recrudescent Ebola virus disease and subsequent fatal meningoencephalitis. We obtained data from epidemiological databases, Ebola treatment units, survivor programme databases, laboratory datasets, and hospital records. Following national protocols established during the 2018-20 outbreak in the Democratic Republic of the Congo, blood, plasma, and cerebrospinal fluid (CSF) samples were collected during the first and second episodes of Ebola virus disease from both individuals and were analysed by molecular (quantitative RT-PCR and next-generation sequencing) and serological (IgG and IgM ELISA and Luminex assays) techniques., Findings: The total time between the end of the first Ebola virus episode and the onset of the second episode was 342 days for patient 1 and 137 days for patient 2. In both patients, Ebola virus RNA was detected in blood and CSF samples during the second episode of disease. Complete genomes from CSF samples from this relapse episode showed phylogenetic relatedness to the genome sequenced from blood samples collected from the initial infection, confirming in-host persistence of Ebola virus. Serological analysis showed an antigen-specific humoral response with typical IgM and IgG kinetics in patient 1, but an absence of an endogenous adaptive immune response in patient 2., Interpretation: We report the first two cases of fatal meningoencephalitis associated with Ebola virus persistence in two survivors of Ebola virus disease who had received vaccination and mAb-based treatment in the Democratic Republic of the Congo. Our findings highlight the importance of long-term monitoring of survivors, including continued clinical, virological, and immunological profiling, as well as the urgent need for novel therapeutic strategies to prevent and mitigate the individual and public health consequences of Ebola virus persistence., Funding: Ministry of Health of the Democratic Republic of the Congo, Institut National de Recherche Biomédicale, Infectious Disease Rapid Response Reserve Fund, US Centers for Disease Control and Prevention, US National Cancer Institute (National Institutes of Health), French National Research Institute for Development, and WHO., Competing Interests: Declaration of interests We declare no competing interests., (Published by Elsevier Ltd.)

We linked 4 mpox cases in South Ubangi, Democratic Republic of the Congo, to transboundary transmission from Central African Republic. Viral genome sequencing demonstrated that the monkeypox virus sequences belonged to distinct clusters of subclade Ia. This finding demonstrates the borderless nature of mpox and highlights the need for vigilant regional surveillance.

Introduction: Long COVID is defined as the continuation of symptoms, unexplainable by alternative diagnosis, longer than four weeks after SARS-CoV-2 infection. These symptoms might hinder daily activities and overall well-being, ultimately impacting quality of life (QoL). Several studies have reported fatigue as the most common symptom, followed by dyspnoea, headache and myalgia. Although it is assumed that long COVID affects 10-20% of SARS-CoV-2 infected individuals, recently numbers up to 60% were described for patients with cancer. This study uncovers the impact of the COVID-19 pandemic on QoL of patients with cancer and how long COVID manifests in this cohort., Methods: A group of 96 patients with cancer was followed from March 2022 till March 2023. Online questionnaires assessing symptoms associated with long COVID, anxiety and depression (HADS), quality of life (EORTC-QLQ-C30) and cognitive functioning (CFQ) were sent every three months during this period. Furthermore, a semi-structured focus group was organised for qualitative data collection., Results: Overall, these patients reported a negative impact of the enforced COVID-19 restrictions on the emotional and psychological wellbeing. Forty nine patients with cancer (51.0%) were infected with SARS-CoV-2 over the course of the study, of which 39 (79.6%) reported long COVID symptoms. The most commonly reported symptoms were myalgia (46.2%), fatigue (38.5%) and disturbed sleep (35.9%) and it was observed that male sex is associated with poor long COVID outcomes., Conclusion: While patients with cancer experience similar long COVID symptoms as healthy controls, the prevalence is remarkably higher possibly due to their compromised immune system and weakened physiological reserve., (© 2024. The Author(s).)

Background: Despite the worldwide progress in cancer diagnostics, more sensitive diagnostic biomarkers are needed. The methylome has been extensively investigated in the last decades, but a low-cost, bisulfite-free detection method for multiplex analysis is still lacking., Methods: We developed a methylation detection technique called IMPRESS, which combines methylation-sensitive restriction enzymes and single-molecule Molecular Inversion Probes. We used this technique for the development of a multi-cancer detection assay for eight of the most lethal cancer types worldwide. We selected 1791 CpG sites that can distinguish tumor from normal tissue based on DNA methylation. These sites were analysed with IMPRESS in 35 blood, 111 tumor and 114 normal samples. Finally, a classifier model was built., Results: We present the successful development of IMPRESS and validated it with ddPCR. The final classifier model discriminating tumor from normal samples was built with 358 CpG target sites and reached a sensitivity of 0.95 and a specificity of 0.91. Moreover, we provide data that highlight IMPRESS's potential for liquid biopsies., Conclusions: We successfully created an innovative DNA methylation detection technique. By combining this method with a new multi-cancer biomarker panel, we developed a sensitive and specific multi-cancer assay, with potential use in liquid biopsies., (© 2024. The Author(s).)

Outbreaks of monkeypox (mpox) have historically resulted from zoonotic spillover of clade I monkeypox virus (MPXV) in Central Africa and clade II MPXV in West Africa. In 2022, subclade IIb caused a global epidemic linked to transmission through sexual contact. Here we describe the epidemiological and genomic features of an mpox outbreak in a mining region in eastern Democratic Republic of the Congo, caused by clade I MPXV. Surveillance data collected between September 2023 and January 2024 identified 241 suspected cases. Genomic analysis demonstrates a distinct clade I lineage divergent from previously circulating strains in the Democratic Republic of the Congo. Of the 108 polymerase chain reaction-confirmed mpox cases, the median age of individuals was 22 years, 51.9% were female and 29% were sex workers, suggesting a potential role for sexual transmission. The predominance of APOBEC3-type mutations and the estimated emergence time around mid-September 2023 imply recent sustained human-to-human transmission., (© 2024. The Author(s).)

Norovirus (NoV) is the predominant cause of foodborne illness globally; current detection methods are typically expensive, have inadequate sensitivities, and utilize biological receptors with poor stability. Therefore, accurate, cost-effective, and highly stable detection methods are needed to screen for NoV in foods. We developed molecularly imprinted polymer nanoparticles (nanoMIPs) to detect NoV using a small target epitope (12 amino acids) with a solid-phase synthesis approach. The performance of three batches of nanoMIPs with varying monomer compositions (nanoMIP-1, -2, and -3) were compared both experimentally and computationally. Surface plasmon resonance examined nanoMIP binding affinity to norovirus virus-like particles (NoV-LPs), whereby nanoMIP-1 had the lowest K D value of 0.512 μM. This is significant, as traditional targets for generation of norovirus ligands previously reported were generated against drastically larger norovirus capsid segments that have limitations in ease of production. Further, an electrochemical sensor was developed by covalently attaching the nanoMIPs to glassy carbon electrodes. In agreement with our predictions from density functional theory simulations, electrochemical impedance spectroscopy showed a sensitive response toward NoV-LPs for nanoMIP batches tested; however, nanoMIP-1 was optimal, with an excellent detection limit of 3.4 pg/mL (1.9 × 10 5 particles/mL). Due to its exceptional performance, nanoMIP-1 was immobilized to screen-printed electrodes and utilized within a thermal sensor, where it exhibited a low detection limit of 6.5 pg/mL (3.7 × 10 5 particles/mL). Crucially, we demonstrated that nanoMIP-1 could detect NoV in real food samples (romaine lettuce) by using electrochemical and thermal sensors. Consequently, the study highlights the exceptional potential of nanoMIPs to replace traditional biological materials (e.g., antibodies) as sensitive, versatile, and highly stable receptors within NoV sensors.

Carboxamidates as equatorial ligands in dirhodium paddlewheel catalysts are widely believed to increase selectivity at the expense of reactivity. The results of the combined experimental and computational approach described in this paper show that one has to beware of such generalizations. First, 103 Rh NMR revealed how strongly primary carboxamidates impact the electronic nature of the rhodium center they are bound to; at the same time, such ligands stabilize donor/acceptor carbenes by engaging their ester carbonyl group into peripheral interligand hydrogen bonding. This array benefits selectivity as well as reactivity if maintained along the entire reaction coordinate of a catalytic cyclopropanation. In settings where the hydrogen bond needs to be distorted for the reaction to proceed, however, it constitutes a significant enthalpic handicap. Representative examples for each scenario were analyzed by DFT; in both cases, the cyclopropanation step rather than carbene formation was found to be turnover-limiting. While this conclusion somehow contradicts the literature, it implied that the direct observation of highly reactive dirhodium carbenes in truly catalytic settings might be possible, even though the intermediates carry olefinic sites amenable to intramolecular cyclopropanation. Such in situ monitoring by NMR is without precedent, yet it was successful with the homoleptic catalyst [Rh 2 (OPiv) 4 ] as well as with its heteroleptic sibling [Rh 2 (OPiv) 3 (acam)] comprising an acetamidate (acam); in the latter case, the carbene bound to the rhodium atom at the [O 3 N]-face was observed, which concurs with the computational data that this species is stabilized by the forecited interligand hydrogen bonding.

The ongoing national mpox outbreak in the Democratic Republic of the Congo has resulted in more >30,000 suspected cases in the country from January 2023 to August 2024. While these historic case totals have been driven by primarily by zoonosis, the emergence of Clade Ib monkeypox virus (MPXV), which is connected to more sustained human-to-human transmission, has been associated with increasing public health impacts in eastern DRC. First identified in South Kivu province, Clade Ib MPXV has been identified in multiple non-endemic East African countries for the first time. In DRC, there have been concerns over broader Clade Ib expansion in the country that could further complicate containment and mitigation responses. Here, we report the first introductions of Clade Ib into North Kivu province, including within internal displacement camps, with suspected close contact transmission that includes non-intimate contacts and children. These findings demonstrate that mpox case investigations and community messaging campaigns should include considerations for non-sexual contact-mediated transmission of Clade Ib that includes children <15 years., Competing Interests: COMPETING INTERESTS None of the other authors declare competing interests.

DNA methylation biomarkers have emerged as promising tools for cancer detection. Common methylation patterns across tumor types allow multi-cancer detection. Droplet digital PCR (ddPCR) has gained considerable attention for methylation detection. However, multi-cancer detection using multiple targets in ddPCR has never been performed before. Therefore, we developed a multiplex ddPCR assay for multi-cancer detection. Based on previous data analyses using The Cancer Genome Atlas (TCGA), we selected differentially methylated targets for eight frequent tumor types (lung, breast, colorectal, prostate, pancreatic, head and neck, liver, and esophageal cancer). Three targets were validated using ddPCR in 103 tumor and 109 normal adjacent fresh frozen samples. Two distinct ddPCR assays were successfully developed. Output data from both assays is combined to obtain a read-out from the three targets together. Our overall ddPCR assay has a cross-validated area under the curve (cvAUC) of 0.948. Performance between distinct cancer types varies, with sensitivities ranging from 53.8% to 100% and specificities ranging from 80% to 100%. Compared to previously published single-target parameters, we show that combining targets can drastically increase sensitivity and specificity, while lowering DNA input. In conclusion, we are the first to report a multi-cancer methylation ddPCR assay, which allows for highly accurate tumor predictions., (© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Over the past decades, the number of arthropod-borne virus (arbovirus) outbreaks has increased worldwide. Knowledge regarding the sylvatic cycle (i.e., non-human hosts/environment) of arboviruses is limited, particularly in Africa, and the main hosts for virus maintenance are unknown. Previous studies have shown the presence of antibodies against certain arboviruses (i.e., chikungunya-, dengue-, and Zika virus) in African non-human primates and bats. We hypothesize that small mammals, specifically rodents, may function as amplifying hosts in anthropogenic environments. The detection of RNA of most arboviruses is complicated by the viruses' short viremic period within their hosts. An alternative to determine arbovirus hosts is by detecting antibodies, which can persist several months. Therefore, we developed a high-throughput multiplex immunoassay to detect antibodies against 15 medically relevant arboviruses. We used this assay to assess approximately 1,300 blood samples of the multimammate mouse, Mastomys natalensis from Tanzania. In 24% of the samples, we detected antibodies against at least one of the tested arboviruses, with high seroprevalences of antibodies reacting against dengue virus serotype one (7.6%) and two (8.4%), and chikungunya virus (6%). Seroprevalence was higher in females and increased with age, which could be explained by inherent immunity and behavioral differences between sexes, and the increased chance of exposure to an arbovirus with age. We evaluated whether antibodies against multiple arboviruses co-occur more often than randomly and found that this may be true for some members of the Flaviviridae and Togaviridae. In conclusion, the development of an assay against a wide diversity of medically relevant arboviruses enabled the analysis of a large sample collection of one of the most abundant African small mammals. Our findings highlight that Mastomys natalensis is involved in the transmission cycle of multiple arboviruses and provide a solid foundation to better understand the role of this ubiquitous rodent in arbovirus outbreaks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 De Kesel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

From the perspective of developing relevant interventions for treating HIV and controlling its spread, it is particularly important to comprehensively understand the underlying diversity of the virus, especially in countries where the virus has been present and evolving since the cross-species transmission event that triggered the global pandemic. Here, we generate and phylogenetically analyse sequences derived from the gag-protease (2010 bp; n  = 115), partial integrase (345 bp; n  = 36), and nef (719 bp; n  = 321) genes of HIV-1 group M (HIV-1M) isolates sampled between 2000 and 2022 from two cosmopolitan cities and 40 remote villages of Cameroon. While 52.4% of all sequenced viruses belonged to circulating recombinant form (CRF) 02&#95;AG (CRF02&#95;AG), the remainder were highly diverse, collectively representing seven subtypes and sub-subtypes, eight CRFs, and 36 highly divergent lineages that fall outside the established HIV-1M classification. Additionally, in 77 samples for which at least two genes were typed, 31% of the studied viruses apparently had fragments from viruses belonging to different clades. Furthermore, we found that the distribution of HIV-1M populations is similar between different regions of Cameroon. In contrast, HIV-1M demographics in Cameroon differ significantly from those in its neighbouring countries in the Congo Basin (CB). In phylogenetic trees, viral sequences cluster according to the countries where they were sampled, suggesting that while there are minimal geographical or social barriers to viral dissemination throughout Cameroon, there is strongly impeded dispersal of HIV-1M lineages between Cameroon and other locations of the CB. This suggests that the apparent stability of highly diverse Cameroonian HIV-1M populations may be attributable to the extensive mixing of human populations within the country and the concomitant trans-national movements of major lineages with very similar degrees of fitness; coupled with the relatively infrequent inter-national transmission of these lineages from neighbouring countries in the CB., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: Interval cancer (IC) is an important quality indicator in colorectal cancer (CRC) screening. Previously, we found that fecal immunochemical test (FIT) ICs are more common in women, older age, right-sided tumors, and advanced stage. Here, we extended our existing stage IV patient cohort with clinicopathological and molecular characteristics, to identify factors associated with FIT-IC., Methods: Logistic regression models were fit to identify variables associated with the odds of having a stage IV FIT-IC. Multivariate models were corrected for gender, age, and location., Results: A total of 292 screen-detected (SD) CRCs and 215 FIT-IC CRCs were included. FIT-IC CRC had 5 fold higher odds to be a neuroendocrine (NET) tumor and 2.5 fold higher odds to have lymphovascular invasion. Interestingly, some variables lost significance upon accounting for location. Thus, tumor location is a critical covariate that should always be included when evaluating factors related to FIT-IC., Conclusions: We identified NETs and lymphovascular invasion as factors associated with increased odds of having a stage IV FIT-IC. Moreover, we highlight the importance of tumor location as a covariate in evaluating FIT-IC related factors. More research across all stages is needed to clarify how these insights might help to optimize the Flemish CRC screening program., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Neefs, Tran, Ferrari, Janssens, Van Herck, Op de Beeck, Van Camp, Peeters, Fransen, Hoeck and Van Hal.)

Between January and August 2024, mpox cases have been reported in nearly all provinces of the Democratic Republic of the Congo (DRC). Monkeypox virus genome sequences were obtained from 11 mpox cases' samples, collected in July-August 2024 in several health zones of Kinshasa. Characterisation of the sequences showed subclades Ia and Ib co-circulating in the Limete health zone, while phylogenetic analyses suggested multiple introductions of the two subclades in Kinshasa. This illustrates the growing complexity of Clade I mpox outbreaks in DRC.

Objectives: This study aimed to investigate the prevalence of orthoebolavirus antibodies in Madina Oula, a non-epidemic rural area in Guinea, in 2022., Methods: A cross-sectional study was conducted from March 14 to April 3, 2022 involving recording household and socio-demographic characteristics, lifestyle data, and collecting dried blood spots from 878 individuals in 235 households. Dried blood spots were tested using multiplex serology to detect antibodies to different orthoebolaviruses: Ebola virus, Bundibugyo virus, Sudan virus, Reston virus, and Bombali virus. Seroprevalence was estimated with a 95% confidence interval and a Z-test was performed to compare the seropositivity between children aged under 15 years and those over 15 years. Household and participant characteristics were analyzed using descriptive statistic, and socio-historical conditions were discussed., Results: The serological analysis conducted in 2022 on 878 participants revealed varying reactivity to orthoebolavirus antigens, notably, with glycoprotein antigens, particularly, glycoprotein Sudan virus (16%). A total of 21 samples exhibited reactivity with at least two antigens, with a median age of 27 years (interquartile range 10.00-35.00), ranging from 2 to 80 years. There is no significant difference between seropositivity in children aged under 15 (2.86%) years and those over 15 (2.14%) years. The antibody presence varied per village, with the highest prevalence observed in Ouassou and Dar-es-Salam., Conclusions: Serological data in a region unaffected by recent Ebola outbreaks indicate possible orthoebolavirus endemicity, emphasizing the need for preparedness against known or novel orthoebolaviruses with potential cross-reactivity., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Venous thromboembolism (VTE) is a common and potentially life-threatening complication in patients with cancer. Both cancer and its treatments increase the risk of developing VTE. Specific cancer types and individual patient comorbidities increase the risk of developing cancer-associated VTE, and the risk of bleeding is increased with anticoagulation therapies. The aims of this article are to summarize the latest evidence for treating cancer-associated VTE, discuss the practical considerations involved, and share best practices for VTE treatment in patients with cancer. The article pays particular attention to challenging contexts including patients with brain, lung, gastrointestinal, and genitourinary tumors and those with hematological malignancies. Furthermore, the article summarizes specific clinical scenarios that require additional treatment considerations, including extremes of body weight, nausea and gastrointestinal disturbances, compromised renal function, and anemia, and touches upon the relevance of drug-drug interactions. Historically, vitamin K antagonists and low-molecular-weight heparins (LMWHs) have been used as therapy for cancer-associated VTE. The development of direct oral anticoagulants has provided additional treatment options, which, in certain instances, offer advantages over LMWHs. There are numerous factors that need to be considered when treating cancer-associated VTE, and although various treatment guidelines are helpful, they do not reflect each unique scenario that may arise in clinical practice. This article provides a summary of the latest evidence and a practical approach for treating cancer-associated VTE., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: EVC: provided consultancy services to AbbVie, Agenus, ALX, Amgen, Arcus Biosciences, Astellas, AstraZeneca, Bayer, Beigene, Bexon Clinical, BioNTech, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Debiopharma, Elmedix, EISAI, Galapagos, GlaxoSmithKline, Hookipa Biotech, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Nordic, Pierre Fabre, Pfizer, Roche, Seattle Genetics, Servier, Simcere, Takeda, Taiho, and Terumo. IM: received grant/research support from Bristol Myers Squibb/Pfizer; and received honoraria and travel/meeting support from Bristol Myers Squibb, Pfizer, and Leo Pharma. EF: participated on advisory boards for AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GlaxoSmithKline, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, Turning Point, and Daiichi Sankyo; received honoraria from Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, Merck Sharp & Dohme, Peervoice, Pfizer, Sanofi, Takeda, and Touch Oncology; received meeting/travel support from AstraZeneca, Janssen, and Roche; and is an independent member of the eboard of Grifols. GA: nothing to disclose. AA: received grant/research support from Bristol Myers Squibb and Roche; received honoraria from Amgen, AstraZeneca, Bayer, Daiichi, EISAI, Genomic Health, Ipsen, Leo Pharma, Lilly, Merck, MSD, Novartis, Pfizer, and Seattle Genetics; and participated on a Data Safety Monitoring Board or advisory board for Amgen, AstraZeneca, Bayer, Daiichi, EISAI, Genomic Health, Hengrui, Innate, Ipsen, Leo Pharma, Lilly, Merck, MSD, Novartis, Pfizer, Seattle Genetics, and Menarini. AC: received research support from AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Pfizer Limited, and Sanofi; provided consultancy services to Alexion, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Centrix Healthcare, Daiichi-Sankyo, Pfizer Limited, and Sanofi; received honoraria from AstraZeneca, Bayer, Bristol Myers Squibb, Centrix Healthcare, Daiichi-Sankyo, Pfizer Limited, and Sanofi; received meeting/travel support from AstraZeneca, Bayer, Bristol Myers Squibb, Centrix Healthcare, Daiichi-Sankyo, Pfizer Limited, and Sanofi; and participated on a Data Safety Monitoring Board or advisory board for AbbVie, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi-Sankyo, and Pfizer Limited. AF: received honoraria from Sanofi, Leo Pharma, and Werfen. MM: nothing to disclose. MP: nothing to disclose. NT: received honoraria from Vianex; and received meeting/travel support from Leo Pharma. PV: received research funding from Bayer, Bristol Myers Squibb, Pfizer, and Leo Pharma; and received honoraria from Bayer, Pfizer, Bristol Myers Squibb, Daiichi-Sankyo, Leo Pharma, and Anthos Therapeutics. CA: received manuscript development support from Bristol Myers Squibb/Pfizer; and provided consultancy services to and received honoraria from Bayer, Bristol Myers Squibb/Pfizer, Daiichi-Sankyo, and Sanofi., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Trastuzumab deruxtecan has shown encouraging activity in patients with treatment-refractory HER2-positive, RAS wild-type and BRAF wild-type metastatic colorectal cancer. Dose optimisation and further antitumour assessments in patients with RAS mutations and those with previous anti-HER2 therapy are warranted. We aimed to evaluate two doses of trastuzumab deruxtecan (5·4 mg/kg and 6·4 mg/kg) to establish the recommended dose in patients with pretreated HER2-positive, RAS wild-type or mutant metastatic colorectal cancer., Methods: DESTINY-CRC02 was a multicentre, randomised, two-stage, two-arm, phase 2 study done in 53 research hospitals and medical centres in Australia, Belgium, France, Italy, Japan, South Korea, Spain, Taiwan, the UK, and the USA. Eligible patients were aged 18 years and older or 20 years and older (depending on region) with pretreated pathologically documented, unresectable, recurrent, or metastatic HER2-positive, and RAS wild-type or mutant colorectal cancer. Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and have received previous chemotherapy, and anti-EGFR, anti-VEGF, or anti-PD-L1 therapy, if clinically indicated. In stage 1, patients were randomly assigned (1:1), via a secure interactive response technology system, to receive 5·4 mg/kg or 6·4 mg/kg trastuzumab deruxtecan administered intravenously every 21 days. Stratification factors were ECOG performance status, HER2 status, and RAS status. In stage 2, patients were assigned into the 5·4 mg/kg treatment group only. The primary endpoint was confirmed objective response rate by blinded independent central review, assessed in all patients for whom treatment was assigned (full analysis set). Safety was assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04744831, and is ongoing (not recruiting)., Findings: Between March 5, 2021, and March 29, 2022, 135 patients were centrally screened, 122 of whom were enrolled. In stage 1, 40 patients each were randomly assigned to receive trastuzumab deruxtecan 5·4 mg/kg and 6·4 mg/kg. In stage 2, an additional 42 patients were enrolled in the 5·4 mg/kg group. 64 (52%) participants were male and 58 (48%) were female. The median duration of follow-up was 8·9 months (IQR 6·7-10·5) in the 5·4 mg/kg group and 10·3 months (5·9-12·7) in the 6·4 mg/kg group. The confirmed objective response rate by blinded independent central review was 37·8% (31/82 [95% CI 27·3-49·2]) in the 5·4 mg/kg group and 27·5% (11/40 [14·6-43·9]) in the 6·4 mg/kg group. 34 (41%) of 83 patients in the 5·4 mg/kg group and 19 (49%) of 39 in the 6·4 mg/kg group had grade 3 or worse drug-related treatment-emergent adverse events. The most common grade 3 or worse drug-related treatment-emergent adverse events were neutrophil count decreased (13 [16%] of 83 patients), anaemia (six [7%]), nausea (six [7%]), and white blood cell count decreased (five [6%]) in the 5·4 mg/kg group; and were neutrophil count decreased (10 [26%] of 39 patients), anaemia (eight [21%]), platelet count decreased (four [10%]), and white blood cell count decreased (four [10%]) in the 6·4 mg/kg group. Drug-related serious adverse events occurred in 11 (13%) of 83 patients in the 5·4 mg/kg group and six (15%) of 39 patients in the 6·4 mg/kg group; the most common in the 5·4 mg/kg group was nausea (three [4%] patients) and the most common in the 6·4 mg/kg group were fatigue (two [5%] patients), neutropenia (two [5%]), and thrombocytopenia (two [5%]). A drug-related treatment-emergent adverse event related to death occurred in one (1%) patient in the 5·4 mg/kg group (due to hepatic failure). Adjudicated drug-related interstitial lung disease or pneumonitis events were observed in seven (8%) patients in the 5·4 mg/kg group (all grade 1 or 2) and in five (13%) patients in the 6·4 mg/kg group (four grade 1 or 2; one grade 5)., Interpretation: The promising antitumour activity and favourable safety profile support trastuzumab deruxtecan 5·4 mg/kg as the optimal single-agent dose for patients with pretreated HER2-positive metastatic colorectal cancer, including those with RAS mutations, previous anti-HER2 therapy, or both., Funding: Daiichi Sankyo and AstraZeneca., Competing Interests: Declaration of interests KR has received research grants from Bayer, UCB BioSciences, Hibercell, Eisai, Merck, Janssen Pharmaceuticals, AbbVie, Daiichi Sankyo, Guardant Health, Innovent Biologics, and Xencor; has received payment or honoraria from Bayer, Daiichi Sankyo, and Seagen; and has participated on a data safety monitoring board or advisory board for Bayer, Eisai/Merck, SAGA Diagnostics, Daiichi Sankyo, Seagen, Pfizer, and AstraZeneca. SS has participated on a data safety monitoring board or advisory board for Agenus, AstraZeneca, Bayer, Bristol Myers Squibb, CheckmAb, Daiichi Sankyo, GlaxoSmithKline, MSD, Merck, Novartis, Pierre Fabre, Seagen, and T-One Therapeutics. AT has received research grants from Daiichi Sankyo, Ono Pharmaceutical, Bristol Myers Squibb, Pfizer, Merck Sharp & Dome, Isofol Medical, Incyte Corporation, and Hutchison Medipharma; and has received payment or honoraria from Eli Lilly, Taiho Pharmaceutical, Ono Pharmaceutical, Chugai Pharma, Merck Serono, and Takeda. TKat has received payment or honoraria from Chugai Pharmaceutical, Ono Pharmaceutical, Takeda Pharmaceutical, and Eli Lilly. FP has received payment or honoraria from Amgen, Merck-Serono, MSD, BMS, Astellas, Johnson & Johnson, Takeda, Bayer, Servier, Pierre Fabre, Ipsen, GSK, and Rottapharm. YK has received royalties or licenses from Ono Pharmaceutical, Chugai Pharmaceutical, Taiho Pharmaceutical, Shionogi, Nippon Zoki Pharmaceuticals, Asahi Kasei Pharma Corporation, Nippon, Kayaku, Daiichi Sankyo, IQVIA Services Japan, MSD, Astellas Pharma, Incyte Corporation, Eisai, National Cancer Center Japan, Syneos Health Clinical, ShiftZero, Parexel International, Japan Clinical Cancer Research Organization, EPS Holdings, Sysmex Corporation, Public Health Research Foundation, Aichi Cancer Center, and Kyushu Study group of Clinical Cancer; and has received payment or honoraria from Ono Pharmaceutical, TAIHO Pharmaceutical, Astellas Pharma, EA Pharma, Daiichi Sankyo, Nippon, Kayaku, Pfizer, Nippon Zoki Pharmaceuticals, Sanofi, NIPRO, MOROO, Alfresa Pharma Corporation, Boehringer Ingelheim, Hakodate National Hospital, Asahi Kasei Pharma Corporation, Chugai Pharmaceutical, MSD, Zeria Pharmaceutical, Bayer Yakuhin, Eli Lilly, Yakult Honsha, Sumitomo Dainippon Pharma, Incyte Corporation, Merck Biopharma, The Japanese Gastroenterological Association, Sapporo Minami Tokushukai Hospital, and Pancan Japan. HK has received consulting or advisory fees from Astellas Pharma, Daiichi-Sankyo, and AbbVie; honoraria from Bristol Myers Squibb, Bayer Yakuhin, Ono Pharmaceutical, Eli Lilly Japan, MSD, Chugai Pharmaceutical, Daiichi-Sankyo, Merck Biopharma, Teijin Pharma, Takeda Pharmaceutical, Yakult Pharmaceutical Industry, Taiho Pharmaceutical, Amgen, Otsuka Pharmaceutical, GlaxoSmithKline, and Nippon Kayaku; and research funding from Bristol Myers Squibb, Kobayashi Pharmaceutical, and Eisai. MP has received research grants from Amgen, Bayer, Bristol Myers Squibb, Ipsen, Novartis, and Roche; has received payment or honoraria from Amgen, Bayer, Bristol Myers Squibb, Merck, MSD, Roche, Sanofi, Servier, and Sirtex; has received consulting fees from Amgen, Bayer, Ipsen, Merck, MSD, Qurin, Remedus, Sanofi, Sirtex, and Terumo; and has participated on a data safety monitoring board or advisory board for Basilea. TA has received payment or honoraria from AstraZeneca, Bristol Myers Squibb, Gritstone Oncology, GlaxoSmithKline, Merck, Pierre Fabre, Seagen, and Servier Transgéne; has received support for attending meetings or travel from Bristol Myers Squibb and Merck; has received consulting fees from Aptitude Health, Astellas, Bristol Myers Squibb, Gritstone Oncology, GamaMabs Pharma, GlaxoSmithKline, Kaleido Oncology, Merck, Pierre Fabre, Seagen, Servier, and Transgène; and is president of the ARCAD Foundation. SL has received research grants from Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Hutchinson, Incyte, Merck Serono, Mirati, MSD, Pfizer, Roche, and Servier; has received payment or honoraria from Amgen, Bristol Myers Squibb, Incyte, GlaxoSmithKline, Eli Lilly, Merck Serono, MSD, Pierre Fabre, Roche, and Servier; and has received consulting fees from Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, GSK, Incyte, Eli Lilly, Merck Serono, MSD, Pierre Fabre, Roche, Takeda, and Servier. KY has received research grants from Taiho Pharm; and has received honoraria from Daiichi Sankyo, Chugai Pharmaceutical, Bristol Myers Squibb, Eli Lilly Japan, Taiho Pharmaceutical, Ono Pharmaceutical, Takeda Pharmaceutical, and Merck. JT has received honoraria from Servier and Pierre Fabre; has received consulting fees from Haystack Oncology; has participated on a data safety monitoring board or advisory board for Gilead, MSD, Bristol Myers Squibb, Pierre Fabre, Novartis, and Daiichi Sankyo; and has participated with leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for Australasian Gastro-Intestinal Trials Group and European Society for Medical Oncology. CGC has received honoraria from Amgen, Merck, Servier, Pierre Fabre, and Incyte; has received support for attending meetings or travel from Merck, Servier, and Pierre Fabre; and is the Secretary of the Spanish Group for Treatment of Gastrointestinal Tumours (TTD). JHS has received research grants from AbbVie, Amgen, AStar D3, Bayer, Curegenix, Daiichi Sankyo, Eli Lilly, Erasca, Gossamer Bio, Leap Therapeutics, Nektar, Roche/Genentech, Sanofi, Seagen, and Silverback Therapeutics; has received payment or honoraria from Seagen, Bayer, and Natera; has received consulting fees from AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Natera, Pfizer, Roche/Genentech, Seagen, Silverback Therapeutics, Takeda, and Viatris; has participated on a data safety monitoring board or advisory board for AbbVie, Pionyr Immunotherapeutics, and Beigene; and has received support for attending meetings or travel from Seagen. YC has received consulting fees from IMBdx, Ono Pharmaceutical, Boryung Pharmaceutical, Interpark Bioconvergence, and GC Genome Corporation; and has received honoraria from Roche and MSD Korea. DB is an employee of Daiichi Sankyo. QY has received employee benefits (stocks or other financial or non-financial interests) from Daiichi Sankyo. TKam has received employee benefits (financial or non-financial interests) from Daiichi Sankyo. KK is an employee of Daiichi Sankyo. AB has received employee benefits (stocks or other financial or non-financial interests) from Daiichi Sankyo; and has received support for attending meetings or travel from Daiichi Sankyo. MK is an employee of Daiichi Sankyo. JDA has received employee benefits (stocks or other financial or non-financial interests) from Daiichi Sankyo. TY has received research grants from Amgen, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, FALCO Biosystems, Genomedia, Molecular Health, MSD, Nippon Boehringer Ingelheim, Ono Pharmaceutical, Pfizer Japan, Roche Diagnostics, Sanofi, Sysmex, and Taiho Pharmaceutical; has received honoraria from Chugai Pharmaceutical, Takeda Pharmaceutical, Merck Biopharma, Bayer Yakuhin, Ono Pharmaceutical, and MSD; and has received consulting fees from Sumitomo Corporation. MVdE, H-CH, and T-YK declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Efficient and site-specific delivery of therapeutics drugs remains a critical challenge in cancer treatment. Traditional drug nanocarriers such as antibody-drug conjugates are not generally accessible due to their high cost and can lead to serious side effects including life-threatening allergic reactions. Here, these problems are overcome via the engineering of supramolecular agents that are manufactured with an innovative double imprinting approach. The developed molecularly imprinted nanoparticles (nanoMIPs) are targeted toward a linear epitope of estrogen receptor alfa (ERα) and loaded with the chemotherapeutic drug doxorubicin. These nanoMIPs are cost-effective and rival the affinity of commercial antibodies for ERα. Upon specific binding of the materials to ERα, which is overexpressed in most breast cancers (BCs), nuclear drug delivery is achieved via receptor-mediated endocytosis. Consequentially, significantly enhanced cytotoxicity is elicited in BC cell lines overexpressing ERα, paving the way for precision treatment of BC. Proof-of-concept for the clinical use of the nanoMIPs is provided by evaluating their drug efficacy in sophisticated three-dimensional (3D) cancer models, which capture the complexity of the tumor microenvironment in vivo without requiring animal models. Thus, these findings highlight the potential of nanoMIPs as a promising class of novel drug compounds for use in cancer treatment., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Introduction: Exposure to family risk factors increases adolescents' chances of attaining a lower educational level. However, some adolescents attain a high educational level despite being exposed to family risk factors such as a lower parental socioeconomic status (SES) or receiving less family support., Method: Using data from the Dutch TRAILS cohort study (N T1  = 2175; M age  = 11.1, SD = 0.55, 50.8% female), we investigated if higher levels of effortful control and peer support can buffer against the negative effects of a lower parental SES and less family support on educational level. Two multinomial logistic regressions were performed (from early to mid-adolescence and from mid-adolescence to young adulthood) with post hoc tests to contrast four ordinal educational levels: practical vocational, theoretical vocational, higher general, and (pre-)university., Results: Adolescents with a higher parental SES were consistently more likely to end up at a higher educational level, but family support was hardly associated with educational level. Neither effortful control nor peer support buffered the associations of parental SES and family support with educational level. Effortful control did have a positive direct (compensatory) effect on the educational level., Conclusion: We conclude that other individual competencies or more structural changes may be more helpful buffers for reducing socioeconomic inequalities in educational attainment., (© 2024 The Author(s). Journal of Adolescence published by John Wiley & Sons Ltd on behalf of Foundation for Professionals in Services to Adolescents.)

Oncologic back pain, infection, inflammation, and trauma are the only specific etiologies of chronic low back pain (CLBP) in contrast to most patients who have non-specific CLBP. In oncologic patients developing CLBP, it is critically important to perform further investigation to exclude spinal metastases (SM).The incidence of cancer is increasing, with 15.7-30% developing SM. In the case of symptomatic SM, we can distinguish three main categories: tumor pain; mechanical pain due to instability, with or without pathologic fractures; and metastatic epidural spinal cord compression (MESCC) or radicular compression. Treatment of SM-related pain is dependent on these categories and consists of symptomatic treatment, target therapy to the bone, radiotherapy, systemic oncologic treatment, and surgery. The care for SM is a multidisciplinary concern, with rapid evolutions in all specialties involved. It is of primordial importance to incorporate the knowledge of specialists in all participating disciplines, such as oncology, radiotherapy, and spinal surgery, to determine the adequate treatment to preserve ambulatory function and quality of life while limiting the burden of treatment if possible. Awareness of potential SM is the first and most important step in the treatment of SM-related pain. Early diagnosis and timely treatment could prevent further deterioration. In this review, we explore the pathophysiology and symptomatology of SM and the treatment options for SM-related pain: tumor pain; mechanical pain due to instability, with or without pathologic fractures; and MESCC or radicular compression.

In sub-Saharan Africa, reported COVID-19 numbers have been lower than anticipated, even when considering populations' younger age. The extent to which risk factors, established in industrialised countries, impact the risk of infection and of disease in populations in sub-Saharan Africa, remains unclear. We estimated the incidence of mild and moderate COVID-19 in urban Mozambique and analysed factors associated with infection and disease in a population-based surveillance study. During December 2020-March 2022, 1,561 households (6,049 participants, median 21 years, 54.8% female, 7.3% disclosed HIV positive) of Polana Caniço, Maputo, Mozambique, were visited biweekly to report respiratory symptoms, anosmia, or ageusia, and self-administer a nasal swab for SARS-CoV-2 testing. Every three months, dried blood spots of a subset of participants (1,412) were collected for detection of antibodies against SARS-CoV-2 spike glycoprotein and nucleocapsid protein. Per 1000 person-years, 364.5 (95%CI 352.8-376.1) respiratory illness episodes were reported, of which 72.2 (95%CI 60.6-83.9) were COVID-19. SARS-CoV-2 seroprevalence rose from 4.8% (95%CI 1.1-8.6%) in December 2020 to 34.7% (95%CI 20.2-49.3%) in June 2021, when 3.0% were vaccinated. Increasing age, chronic lung disease, hypertension, and overweight increased risk of COVID-19. Older age increased the risk of SARS-CoV-2 seroconversion. We observed no association between socio-economic status, behaviour and COVID-19 or SARS-CoV-2 seroconversion. Active surveillance in an urban population confirmed frequent COVID-19 underreporting, yet indicated that the large majority of cases were mild and non-febrile. In contrast to reports from industrialised countries, social deprivation did not increase the risk of infection nor disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ingelbeen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The liver is the most frequent site of metastases in colorectal cancer (CRC). This study aimed to assess the response rate and survival outcomes in metastatic CRC patients with non-liver metastases (NLM) compared to those with liver metastases (LM) across different lines of treatment., Methods: A total of 17,924 mCRC patients included in 26 trials from the ARCAD CRC database were analyzed. The analysis was conducted based on the presence or absence of LM across different treatment groups: chemotherapy (CT) alone, CT + anti-VEGF, CT + anti-EGFR in KRAS wild-type tumors, within the first-line (1 L) and second-line (2 L), and patients enrolled in third-line (≥3 L) trials treated with trifluridine/tipiracil or regorafenib or placebo. The endpoints were overall survival (OS), progression-free survival (PFS), and overall response rate (ORR)., Results: Out of the 17,924 patients, 14,066 had LM (30.6 % with only liver involvement and 69.4 % with liver and other metastatic sites), while 3858 patients had NLM. In the CT alone and CT + anti-VEGF subgroups, NLM patients showed better OS and PFS in the 1 L and 2 L settings. However, in the CT + anti-EGFR 1 L and 2 L subgroups, there was no significant difference in OS and PFS between NLM and LM patients. In the ≥ 3 L subgroups, better OS and PFS were observed in NLM patients. ORRs were higher in LM patients than in NLM patients across all cohorts treated in the 1 L and only in the anti-EGFR cohort in the 2 L., Conclusion: LM is a poor prognostic factor for mCRC increasing from 1 L to ≥ 3 L except for patients in 1 L and 2 L receiving CT+anti-EGFR. These data justify using LM as a stratification factor in future trials for patients with unresectable mCRC., Competing Interests: Declaration of Competing Interest Benoist Chibaudel reports consulting and advisory role from Amgen, Bayer, Beigine, Biocartis, Lilly, Merck, MSD, Pfizer, Pierre Fabre, Revolution Medicines, Roche, SeqOne, Sanofi, Servier, Takeda. Josep Tabernero reports personal financial interest in form of scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiff Oncology, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna Inc, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Scandion Oncology, Scorpion Therapeutics, Seattle Genetics, Servier, Sotio Biotech, Taiho, Tessa Therapeutics, TheraMyc and Tolremo Therapeutics. Stocks: Oniria Therapeutics and also educational collaboration with Imedex/HMP, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource (PER). Qian Shi reports consulting/advisory role from Yiviva Inc, Boehringer Ingelheim Pharmaceuticals, Inc, Regeneron Pharmaceuticals, Inc., Hoosier Cancer Research Network, Kronos Bio, and Mirati Therapeutics Inc; Honorarium/speaker role from Chugai Pharmaceutical Co., Ltd (to myself), research funds from Celgene/BMS, Roche/Genentech, Janssen, Novartis (to institution). Thierry Andre reports attending advisory board meetings and receiving consulting fees from Abbvie, Astellas, Aptitude Health, Bristol Myers Squibb, Gritstone Oncology, Gilead, GlaxoSmithKline, Merck & Co. Inc., Nordic Oncology, Seagen, Servier, Takeda and Transgène and honoraria from Bristol Myers Squibb, GlaxoSmithKline, Merck & Co. Inc., Merck Serono, Pierre Fabre, Roche, Sanofi, Seagen and Servier; and support for meetings from Merck & Co. Inc. and Servier. John Zalcberg reports leadership from ICON Group, Lipotek, PRAXIS; Stock from Biomarin, Ophthea, Amarin, Concert Pharmaceuticals, Frequency Therapeutics, Gilead, Madrigal Pharmaceuticals, UniQure, Zogenix, Orphazyme, Moderna Therapeutics, TWST, Novavax, Teladoc; Honoraria from Gilead Sciences, MSD Oncology, Viatris; Consulting & Advisory Role from Merck Sharp & Dohme, Specialized Therapeutics, CEND, Deciphera, REVOLUTION MEDICINE, FivePHusion, Genorbio, 1Global, Novatech, Alloplex Biotherapeutics Inc, Oncology Republic; Research Funding from BMS, AstraZeneca, Pfizer, IQvia, Mylan, Ipsen, Eisai, Medtronic, MSD Oncology, Servier; Travel from MSD Oncology, ICON Group, PRAXIS.Eric Van Cutsem repors participation to advisory boards for Abbvie, ALX, Amgen, Array, Astellas, Astrazeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi, GSK, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Nordic, Pierre Fabre, Pfizer, Roche, Seattle Genetics, Servier, Takeda, Terumo, Taiho, Zymeworks; research grants from Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier paid to his institution. Takayuki Yoshino reports honoraria from Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Bayer Yakuhin, Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K.; consulting fee from Sumitomo Corp.; research grant from Amgen K.K., Bristol-Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd, FALCO biosystems Ltd., Genomedia Inc., MEDICAL & BIOLOGICAL LABORATORIES CO., LTD., Merus N.V., Molecular Health GmbH, MSD K.K., Nippon Boehringer Ingelheim Co ., Ltd., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc.,Roche Diagnostics K.K., Sanofi K.K., Sysmex Corp., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd. Richard Adams reports receiving consulting fees from Takeda, Bayer, GSK; honoraria from Amgen, Bayer, Seagen; Support for attending meetings and/or travel from Servier, Takeda; Participation on Advisory Board from Takeda, Seagen. Carsten Bokemeyer repors receiving consulting fees as advisory boards from Astra Zeneca, Bayer Healthcare, BioNTech, Heaxal, Lindis Biotech, and Sanofi Aventis; as Invited Speaker from AOK Germany, med update, and Roche Pharma; reports honoraria from DGHO, Hamburg Cancer Society, National Network of German Cancer Centers (DKH), Northern German Society of Internal Medicine, DGHO, German Cancer Society. Cornelis J. A. Punt repors receiving consulting fees as advisory boards from Nordic Pharma. Richard M Goldberg receiving consulting fees as advisory boards from Fight for Colorectal Cancer, US NCI. Volker Heinemann repors receiving consulting fees from Merck, Amgen, Roche, AstraZeneca, Celgene, Servier, Novartis, Pierre-Fabre, Halozyme, MSD, BMS, GSK, Janssen, Terumo, Sirtex, Oncosil, Nordic, Boehringer-Ingelheim; honoraria from Merck, Amgen, Roche, Sanofi, Servier, Pfizer, Pierre-Fabre, AstraZeneca, BMS, MSD, Novartis, Boehringer-Ingelheim, Celgene, Sirtex, Seagen, GSK; support for attending from Merck, Amgen, MSD, Nordic, AstraZeneca, Servier: reports stock from BionTech. Chiara Cremolini repors receiving consulting fees from Nordic Pharma, Merck, Pierre Fabre, Servier, Takeda; reports honoraria from Takeda, MSD, Amgen, Merck, Pierre Fabre, Servier, Bayer; participation to advisory board from Mirat. Miriam Koopman repors receiving consulting fees from Bayer, Bristol Myers Squibb, Merck, Personal Genome Diagnostics (PGDx), Pierre Fabre, Roche, Sirtex, Servier and PI participation from the international cohort study PROMETCO with Servier as sponsor; participation to advisory board from Eisai, Nordic Farma, Merck-Serono, Pierre Fabre, Servier; as leadership or fiduciary role in Chair ESMO RWDD working group, co-chair DCCG, PI PLCRC (national observational cohort study), involved in several clinical trials as PI or co-investigator in CRC. Alan Venook repors receiving consulting fees from Amgen, Genentech/Roche, Deciphera; participation on Advisory Board in Amgen, Agenus. Timothy Maughan repors receiving consulting fees from Merck KGAa, Cancer Research UK, Astrazeneca, Ground Truth Laboratories, Perspectum, Nordin Pharma; participation on Advisory Board and leadership in Cancer Research UK, National Cancer Research Institute-University of Liverpool. All remaining authors have declared no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: This study aimed to demonstrate that the genomic material of SARS-CoV-2 can be isolated from strips of COVID-19 rapid diagnostic test cassettes., Method: It was a prospective cross-sectional study involving patients admitted to treatment centers and sampling sites in the city of Conakry, Guinea. A total of 121 patients were double sampled, and 9 more patients were tested only for RDT. PCR was conducted according to the protocol of the RunMei kit. Sequencing was performed by using the illumina COVIDSeq protocol. Nine COVID-19 RDTs without nasopharyngeal swabs were in addition tested., Result: Among the 130 COVID-19 RDTs, forty-seven were macroscopically positive, whereas seventy-two were positive according to PCR using RDT strip, while among the 121 VTM swabs, sixty-four were positive. Among eighty-three negative COVID-19 RDTs, twenty-seven were positive by PCR using RDT strip with a geometric mean Ct value of 32.49 cycles. Compared to those of PCR using VTM, the sensitivity and specificity of PCR using RDT strip were estimated to be 100% and 85.96%, respectively, with 93.39% test accuracy. Among the fifteen COVID-19 RDT extracts eligible for sequencing, eleven had sequences identical to those obtained via the standard method, with coverage between 75 and 99.6%., Conclusion: These results show that COVID-19 RDTs can be used as biological material for the genomic surveillance of SARS-CoV-2., (© 2024. The Author(s).)

Bombali virus (BOMV) is a novel Orthoebolavirus that has been detected in free-tailed bats in Sierra Leone, Guinea, Kenya, and Mozambique. We screened our collection of 349 free-tailed bat lungs collected in Côte d'Ivoire and Tanzania for BOMV RNA and tested 228 bat blood samples for BOMV antibodies. We did not detect BOMV-specific antibodies but found BOMV RNA in a Mops condylurus bat from Tanzania, marking the first detection of an ebolavirus in this country. Our findings further expand the geographic range of BOMV and support M. condylurus ' role as a natural BOMV host.

Background: There is an unmet medical need for the early detection of immune checkpoint inhibitor (ICI)-induced cardiovascular (CV) adverse events due to a lack of adequate biomarkers. This study aimed to provide insights on the incidence of troponin elevations and echocardiographic dynamics during ICI treatment in cancer patients and their role as potential biomarkers for submyocardial damage. In addition, it is the first study to compare hs-TnT and hs-TnI in ICI-treated patients and to evaluate their interchangeability in the context of screening. Results: Among 59 patients, the mean patient age was 68 years, and 76% were men. Overall, 25% of patients received combination therapy. Although 10.6% [95% CI: 5.0-22.5] of the patients developed troponin elevations, none experienced a CV event. No significant changes were found in 3D left ventricular (LV) ejection fraction nor in global longitudinal strain f (56 ± 6% vs. 56 ± 6%, p = 0.903 and -17.8% [-18.5; -14.2] vs. -17.0% [-18.8; -15.1], p = 0.663) at 3 months. There were also no significant changes in diastolic function and right ventricular function. In addition, there was poor agreement between hs-TnT and hs-TnI. Methods: Here, we present a preliminary analysis of the first 59 patients included in our ongoing prospective clinical trial (NCT05699915) during the first three months of treatment. All patients underwent electrocardiography and echocardiography along with blood sampling at standardized time intervals. This study aimed to investigate the incidence of elevated hs-TnT levels within the first three months of ICI treatment. Elevations were defined as hs-TnT above the upper limit of normal (ULN) if the baseline value was normal, or 1.5 ≥ times baseline if the baseline value was above the ULN. Conclusions: Hs-TnT elevations occurred in 10.6% of the patients. However, no significant changes were found on 3D echocardiography, nor did any of the patients develop a CV event. There were also no changes found in NT-proBNP. The study is still ongoing, but these preliminary findings do not show a promising role for cardiac troponins nor for echocardiographic dynamics in the prediction of CV events during the early stages of ICI treatment.

Competing Interests: JBN is supported by the US National Institutes of Health (grant numbers NIH/FIC 1R25TW011217-01, NIH/FIC 1D43TW010937-01A1, NIH/FIC D43TW011827-01A1, NIH/FIC 1R21TW011706-0, and NIH/NIAID 5U01AI096299-13). FN and AZ are codirectors of the Pan-African Network on Emerging and Re-Emerging Infections funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) within the EU Horizon 2020 Framework Programme. FN and AZ also acknowledge support from the EDCTP Central Africa Clinical Research Network. AZ is a UK National Institute for Health Research senior investigator, and a Mahathir Science Award and EU-EDCTP Pascoal Mocumbi Prize laureate. JJM-T holds National Institutes of Health National Institute of Allergy and Infectious Diseases grants (number 75N91019D00024-P00001-759102000025-5). JK is supported by grant funding from the Canadian Institutes of Health Research and International Development Research Centre (grant numbers MRR-184813 and PPE-185821). ELM is supported by the US National Institutes of Health (grant number 1R01AI182082-01). All other authors declare no competing interests. We thank John L Johnson for critical review and helpful advice. The views and conclusions in this Personal View are those of the authors and do not necessarily represent the views of their institutions.

Introduction: Osteolytic spinal metastases (SM) have a higher risk of fracture. In this study we aim to confirm the remineralization of lytic SM after radiation therapy. Secondary the influence of SBRT compared to cEBRT and tumor type will be analyzed., Methods: A retrospective cohort study was performed., Results: 87 patients, 100 SM were included. 29 received SBRT, 71 cEBRT. Most common primary tumors were breast (35 %), lung (26 %) and renal (11 %). Both cEBRT and SBRT resulted in a significant increase of bone mineral density (BMD) (83.76 HU ± 5.72 → 241.41 HU ± 22.58 (p < 0.001) and 82.45 ± 9.13 → 179.38 ± 47.83p = 0.026). There was a significant increase in absolute difference of BMD between the SM and reference vertebrae (p < 0.001). There was no significant difference between SBRT and cEBRT. There was no increase of BMD in renal lytic SM after radiation therapy (pre-treatment: 85.96 HU ± 19.07; 3 m 92.00 HU ± 21.86 (p = 0.882); 6 m 92.06 HU ± 23.94 (p = 0.902); 9 m 70.44 HU ± 7.45 (p = 0.213); 12 m 98.08 HU ± 11.24 (p = 0.740)). In all other primary tumors, a significant increase of BMD after radiation therapy was demonstrated (p < 0,05)., Conclusion: We conclude that the BMD of lytic SM increases significantly after radiation therapy. Lytic SM of primary renal tumors are the exception; there is no significant remineralization of renal lytic SM after radiation therapy. There is no benefit of SBRT over cEBRT in this remineralization. These findings should be taken into account when deciding on surgery in the potentially unstable group defined by the spinal instability neoplastic score., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Introduction: Serological surveys offer the most direct measurement to define the immunity status for numerous infectious diseases, such as COVID-19, and can provide valuable insights into understanding transmission patterns. This study describes seroprevalence changes over time in the context of the Democratic Republic of Congo, where COVID-19 case presentation was apparently largely oligo- or asymptomatic, and vaccination coverage remained extremely low., Methods: A cohort of 635 health care workers (HCW) from 5 health zones of Kinshasa and 670 of their household members was interviewed and sampled in 6 rounds between July 2020 and January 2022. At each round, information on risk exposure and a blood sample were collected. Serology was defined as positive when binding antibodies against SARS-CoV-2 spike and nucleocapsid proteins were simultaneously present., Results: The SARS-CoV-2 antibody seroprevalence was high at baseline, 17.3% (95% CI 14.4-20.6) and 7.8% (95% CI 5.5-10.8) for HCW and household members, respectively, and fluctuated over time, between 9% and 62.1%. Seropositivity was heterogeneously distributed over the health zones (p < 0.001), ranging from 12.5% (95% CI 6.6-20.8) in N'djili to 33.7% (95% CI 24.6-43.8) in Bandalungwa at baseline for HCW. Seropositivity was associated with increasing rounds adjusted Odds Ratio (aOR) 1.75 (95% CI 1.66-1.85), with increasing age aOR 1.11 (95% CI 1.02-1.20), being a female aOR 1.35 (95% CI 1.10-1.66) and being a HCW aOR 2.38 (95% CI 1.80-3.14). There was no evidence that HCW brought the COVID-19 infection back home, with an aOR of 0.64 (95% CI 0.46-0.91) of seropositivity risk among household members in subsequent surveys. There was seroreversion and seroconversion over time, and HCW had a lower risk of seroreverting than household members (aOR 0.60 (95% CI 0.42-0.86))., Conclusion: SARS-CoV-2 IgG antibody levels were high and dynamic over time in this African setting with low clinical case rates. The absence of association with health profession or general risk behaviors and with HCW positivity in subsequent rounds in HH members, shows the importance of the time-dependent, and not work-related, force of infection. Cohort seroprevalence estimates in a 'new disease' epidemic seem insufficient to guide policy makers for defining control strategies., (© 2024. The Author(s).)

Objective : Leadership discussion, including leadership development programs, is common. However, discussion of followership as a component of leadership seems less frequently discussed. With a focus on leadership and followership, this investigation reviewed the health-professions education literature and characterized leadership-followership within health-professions education. Methods : Using PubMed, ERIC, and Google Scholar, two investigators independently and systematically searched health-professions education literature for articles related to leadership and followership. Reports were categorized based on the articles by type, application, profession, leadership, and followership qualities. Results : Eighty-one articles were included. More than half [59% (48/81)] were theoretical, 27% (22/81) empirical, 7% (6/81) commentaries, and 6% (5/81) letters-to-the-editor). Empirical studies did not share outcomes that could be meaningfully combined quantitatively by meta-analysis; however, the vast majority (96%) of theoretical articles discussed a healthcare-related application of leadership and followership (e.g., improving patient care, improving communication, improving organizational efficiency). Thus, a qualitative review was completed. Of the 81 articles, 57% (n=46) involved multiple professions, while 43% (n=35) focused on a specific profession [Nursing (n=16), Medicine (n=7), Others (n=5) Surgery (n=3), Pharmacy (n=2), Veterinary Medicine (n=2)]. While most articles (75%) discussed leadership qualities (with top qualities of effective communication, visionary, and delegating tasks), fewer (57%) discussed followership qualities (with top qualities of being responsible, committed, and supportive). Of note, some qualities overlapped in both leadership and followership (with top qualities of effective communication, being supportive, and providing/receiving feedback). Conclusions : Leadership-Followership was described in many health-professions' education literature. However, Pharmacy and Veterinary Medicine had substantially fewer articles published on this topic. Notably, followership did not receive nearly as much attention as leadership. Leadership has a dynamic and complex interaction with followership highlighting that an effective leader must know how to be an effective follower and vice versa. To improve leadership within healthcare teamwork, education should focus on both leadership-followership., (© Individual authors.)

After cochlear implant (CI) insertion, there is a possibility of postoperative inflammation, which may involve proinflammatory markers such as interleukin-6. Detecting this inflammation promptly is crucial for administering anti-inflammatory drugs, if required. One potential method for detecting inflammation is using molecular imprinted polymers (MIPs). These MIPs, which can be deposited on the CI electrode, provide readout employing impedance measurements, a feature already available on the CI circuit. MIPs designed for this purpose should possess biocompatibility, conductivity, and degradability. The degradability is crucial because there is a limitation on the number of electrodes available, and once the inflammation sensor degrades after the acute inflammation period, it should remain usable as a regular electrode. In this work, conductive poly(3,4-ethylenedioxythiophene) polystyrenesulfonate-based MIPs were synthesized against biotin as a surrogate target marker. Specific biotin binding with MIPs was determined before and after degradation using electrochemical impedance spectroscopy (EIS) and compared with the control nonimprinted polymers (NIPs). Subsequently, MIPs were electrochemically degraded by EIS with different potentials, wherein a potential dependence was observed. With decreasing potential, fewer dissolved polymers and more monomer molecules were detected in the solution in which degradation took place. At a potential of 0.205 V a negligible amount of dissolved polymer in addition to the dissolved monomer molecules was measured, which can be defined as the limiting potential. Below this potential, only dissolved monomer molecules are obtained, which enables renal clearance. Biocompatibility testing revealed that both the polymer and the solution with dissolved monomer molecules do not exceed the ISO 10993-5 cytotoxicity threshold. Based on these findings, we have developed conductive, biocompatible, and controllably degradable MIPs capable of detecting biotin. This research work paves the way for the advancement of CIs, where inflammation can be detected using molecular imprinting technology without compromising the stability and biosafety of the product., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Purpose: Research is inconclusive with respect to the possible risk-increasing effect of anxiety symptoms on heavy drinking behavior among adolescents and young adults. Adult role transitions and changes in the social context from early adolescence into young adulthood may impact the association between anxiety symptoms and alcohol use., Methods: The TRacking Adolescents' Individual Lives Survey, including 2,229 individuals at baseline, was used to evaluate the bi-directional and longitudinal associations between anxiety symptoms and alcohol use, using data at 14, 16, 19, 22, and 25 years of age., Results: Cross-lagged models revealed a relatively stable negative association at 14, 16, and 19 years, showing that relatively higher anxiety symptoms were associated with relatively lower drinking levels three years later. This effect was absent in young adulthood. There was no evidence for significant associations between alcohol use and subsequent anxiety symptoms, with the exception of alcohol use at age 19, which predicted relatively lower levels of anxiety symptoms at age 22., Discussion: Overall, the results indicated that anxiety symptoms may withhold adolescents from (heavy) drinking, although this protective effect disappeared in young adulthood. Transitions in social contexts as well as autonomy and adult responsibilities could underlie the changing association between alcohol use and anxiety symptoms throughout adolescence and young adulthood., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

The first-line treatment choice of EGFRIs plus doublet chemotherapy vs. bevacizumab plus doublet chemotherapy remains a topic of interest for patients with left-sided RAS WT mCRC. We conducted a systematic literature review and meta-analysis of clinical trial data published between 2015 and 2024. We evaluated the relative efficacy and safety of first-line EGFRIs plus doublet chemotherapy (FOLFIRI or FOLFOX) vs. bevacizumab plus doublet chemotherapy for patients with RAS WT left-sided mCRC, as well as in all- and right-sided tumors. We identified eight trials with 2624 patients. Five trials reported outcomes by tumor sidedness. In the left-sided population, overall survival (OS) (Hazard Ratio (HR) = 0.80, 95% Confidence Interval (CI): 0.71-0.90) and objective response rate (ORR) (Odds ratio [OR]=1.61, 95% CI: 1.30-1.99) favored EGFRI plus chemotherapy, while no statistically significant differences were observed for progression-free survival (PFS) (HR=0.93, 95% CI: 0.84-1.04) or resection rate (RR). Similar results were found in the all-sided population. In the right-sided population, PFS favored bevacizumab plus chemotherapy (HR=1.45, 95% CI: 1.19-1.78), while no statistically significant differences were observed for OS (HR=1.17, 95% CI: 0.95-1.44), ORR (OR=0.99, 95% CI: 0.69-1.41), and RR. Early tumor shrinkage in the all-sided population favored EGFRI plus chemotherapy (OR=1.72; 95% CI: 1.36-2.17); limited data precluded evaluation by sidedness. Safety was available in 6 trials for all-sided tumors and 1 trial for left-sided tumors, each demonstrating typical class-specific adverse events. This most comprehensive meta-analysis indicates a benefit for first-line EGFRI plus chemotherapy over bevacizumab plus chemotherapy in patients with left-sided RAS WT mCRC., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: N. Hooda, M. Suh, H. Reichert, and J. Fryzek are employees of EpidStrategies, A Division of ToxStrategies, LLC. and received a grant from Amgen for this research. N. Hooda has also received research funding from Sanofi, and SpringWorks Therapeutics. M. Rehn, V. Chia, D. Younan, K. Mezzi are employees of Amgen and may hold shares and/or stock options in the company. J. Soeda is an employee of Takeda and may hold shares/and or stock options in the company. F. Rivera has served on advisory boards for Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene, Lilly, Merck Serono, MSD, Roche, Sanofi-Aventis, and Servier. He has received research funding from Amgen, Bayer, Celgene, Lilly, Merck Serono, MSD, Roche, Sanofi-Aventis, and Servier. He has received honoraria for talks/presentations from Amgen, Bayer, Bristol Myers Squibb, Celgene, Lilly, Merck Serono, MSD, Roche, Sanofi-Aventis, and Servier. He has received grant support from Amgen, Bristol Myers Squibb, and MSD. K. Muro has received grants from Amgen, Chugai, Sanofi, Astellas, Eisai, Novartis, Pfizer, MSD, ONO Pharmaceutical, Daiichi Sankyo, Taiho. He has received personal fees from Amgen, MSD, ONO Pharmaceutical, Daiichi Sankyo, Taiho, Takeda, Bristol-Myers Squibb, Eli Lilly, and AstraZeneca, outside the submitted work. K. Shitara has received personal fees for consulting and advisory roles from Bristol Myers Squibb, Takeda, Ono Pharmaceutical, Novartis, Daiichi Sankyo, Amgen, Boehringer Ingelheim, Merck Pharmaceutical, Astellas, Guardant Health Japan, Janssen, AstraZeneca, Zymeworks Biopharmaceuticals, ALX Oncology Inc., and Bayer. He has received honoraria from Bristol-Myers Squibb, Ono Pharmaceutical, Janssen, Eli Lilly, Astellas, and AstraZeneca. He has also received research funding (all to institution) from Astellas, Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Chugai, Merck Pharmaceutical, Amgen, Eisai, PRA Health Sciences and Syneos Health, outside the submitted work. M. Peeters has served on advisory boards for Amgen, Bayer, Bimini, Ipsen, Merck, MSD, Qurin, Remedus, Sanofi, Sirtex, and Terumo. He has received speaker fees from Amgen, Bayer, Bristol-Myers Squibb, Merck, MSD, Roche, Sanofi, Servier, and Sirtex. He reports scientific grants from Amgen (inst.), Bayer (inst.), Bristol-Myers Squibb (inst.), Ipsen (inst.), Novartis (inst.), and Roche (inst.). S. Stintzing is an employee of Charité – Universitaetsmedizin Berlin. He has served on advisory boards for Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, ESAI, Lilly, Merck KgaA, MSD, Pierre-Fabre, Roche, Sanofi, Servier, Taiho, and Takeda. He has received honoraria for talks/presentations and advisory board participation from Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, ESAI, Leo-Pharma, Lilly, Merck KgaA, MSD, Pierre-Fabre, Roche, Sanofi, Servier, Taiho, and Takeda. He has received research funding from Merck KgaA, Pierre-Fabre, Roche, and Servier. He has educational collaborationS with Medscape Foundation and COR2ED. He is a member of ASCO, ESMO, DKG, AIO, and DHGO. T. Yoshino has received honoraria from Chugai Pharma, Takeda Pharma, Merck, Bayer Yakuhin, Ono Pharmaceutical, and MSD K.K. He has received consulting fees from Sumitomo Corp. and research grants from Amgen, Chugai, Daiichi Sankyo, Eisai, FALCO Biosystems, Genomedia Inc., Molecular Health, MSD, Nippon Boehringer Ingelheim, Ono, Pfizer, Roche Diagnostics, Sanofi, Sysmex, and Taiho. V. Heinemann has received honoraria Amgen, Merck, Roche, Sanofi, SIRTEX, Servier, Pfizer, Pierre-Fabre, Astra-Zeneca, MSD, GSK, and Seagen. He participated in consulting and advisory boards for Merck, Amgen, Roche, Sanofi, SIRTEX, Bristol-Myers Squibb, MSD, Novartis, Boehringer Ingelheim, Servier, Pierre-Fabre, Celgene, Terumo, GSK, Oncosil, Nordic, and Seagen. He reports research funding (institution) from Merck, Amgen, Roche, Sanofi, Pfizer, Boehringer-Ingelheim, Sirtex, Bayer, and Servier. He has received travel support from Merck Roche, Amgen, SIRTEX, Bayer, Servier, MSD, and GSK. All remaining authors have declared no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The social gradient in adolescent mental health is well established: adolescents' socioeconomic status is negatively associated with their mental health. However, despite changes in social cognition during adolescence, little is known about whether social cognitions mediate this gradient. Therefore, this study tested this proposed mediational path using three data waves, each 6 months apart, from a socioeconomically diverse sample of 1,429 adolescents ( M age = 17.9) in the Netherlands. Longitudinal modeling examined whether three social cognitions (self-esteem, sense of control, and optimism) mediated associations between perceived family wealth and four indicators of adolescent mental health problems (emotional symptoms, conduct problems, hyperactivity, and peer problems). There was evidence of a social gradient: adolescents with lower perceived family wealth reported more concurrent emotional symptoms and peer problems and an increase in peer problems 6 months later. Results also showed evidence of mediation through social cognitions, specifically sense of control: adolescents with lower perceived family wealth reported a decrease in sense of control (though not self-esteem nor optimism) 6 months later, and lower sense of control predicted increases in emotional symptoms and hyperactivity 6 months later. We found concurrent positive associations between perceived family wealth and all three social cognitions, and concurrent negative associations between social cognitions and mental health problems. The findings indicate that social cognitions, especially sense of control, may be an overlooked mediator of the social gradient in adolescent mental health.

Background: Despite the recognized benefits of structured cancer screening, tests outside organized screening programs are common. Comprehensive reports on outside program screening in Europe are lacking, but the Flemish breast cancer (BC) and colorectal cancer (CRC) screening programs monitor data on non-organized tests prescribed by GPs and specialists., Methods: Using data at aggregated level, logistic regression was used to examine the relationship between health care utilization and screening coverage in 308 Flemish municipalities during 2015-18., Results: With regards to BC, municipalities with higher rates of gynecologists' visits had lower odds of coverage inside (-8%) and higher odds of coverage outside (+17%) the program. By contrast, municipalities with higher rates of GP visits, had higher odds of coverage inside (+6%) and lower odds of coverage outside (-7%) the program. As for CRC, municipalities with higher rates of visits gastroenterologists' visits had lower odds of coverage inside (-3%). Instead, municipalities with higher rates of GP visits, had higher odds of coverage both inside (+2%) and outside (+5%) the program. Municipalities with higher percentages of people with chronic conditions had higher odds of coverage within both the BC and CRC programs (+5% and +3%), and lower odds of outside screening (-7% and -6%). Municipalities with higher percentages of people 65+ with dementia and with mood disorders had, respectively, higher odds (+13% and +5%) and lower odds (-3% and -4%) of coverage inside both the BC and CRC programs., Conclusion: Our findings underscore the impact of healthcare utilization on cancer screening coverage at the municipal level in Flanders., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: Some high-grade cervical lesions and cervical cancers (HSIL+) test negative for human papillomavirus (HPV). The HPV-negative fraction varies between 0.03 % and 15 % between different laboratories. Monitoring and extended re-analysis of HPV-negative HSIL+ could thus be helpful to monitor performance of HPV testing services. We aimed to a) provide a real-life example of a quality assurance (QA) program based on re-analysis of HPV-negative HSIL+ and b) develop international guidance for QA of HPV testing services based on standardized identification of apparently HPV-negative HSIL+ and extended re-analysis, either by the primary laboratory or by a national HPV reference laboratory (NRL)., Methods: There were 116 initially HPV-negative cervical specimens (31 histopathology specimens and 85 liquid-based cytology samples) sent to the Swedish HPV Reference Laboratory for re-testing. Based on the results, an international QA guidance was developed through an iterative consensus process., Result: Standard PCR testing detected HPV in 55.2 % (64/116) of initially "HPV-negative" samples. Whole genome sequencing of PCR-negative samples identified HPV in an additional 7 samples (overall 61.2 % HPV positivity). Reasons for failure to detect HPV in an HSIL+ lesion are listed and guidance to identify cases for extended re-testing, including which information should be included when referring samples to an NRL are presented., Conclusion: Monitoring the proportion of and reasons for failure to detect HPV in HSIL+ will help support high performance and quality improvement of HPV testing services. We encourage implementation of QA strategies based on re-analysis of "HPV negative" HSIL+ samples., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: K Cuschieri's institution has received research funding or gratis consumables to support research from the following commercial entities in the last 3 years: Cepheid, Euroimmun, GeneFirst, SelfScreen, Hiantis, Seegene, Roche, Abbott, Hologic and Vaccitech. M.P.’s institution received research funding, free-of-charge reagents, and consumables to support research in the last 3 years from Qiagen, Seegene, Abbott, and Roche, all paid to his employer. Sciensano the employer of M.A. received funding in the framework of Valgent and VALHUDES, which are 2 researcher induced protocols for evaluation of HPV tests on cervical and vaginal samples respectively (see Arbyn et J Clin Virol 2016 & 2018). M.A, did not receive any financial or material benefit from these projects., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)