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Purpose: Randomized studies demonstrated the oncological equivalence of (ultra-)hypofractionation compared to a 5-week schedule in postoperative radiotherapy of breast cancer. Due to the low incidence and long latency of secondary malignancies, there are currently no reliable clinical data regarding the influence of fractionation regimens on the development of secondary malignancies., Material and Methods: For 20 patients with right or left-sided breast cancer, postoperative treatment plans were created using 3D-CRT (n = 10) or VMAT (n = 10) for three different fractionation schedules: 5-week schedule with 50.4Gy in 1.8Gy (28fx), hypofractionation with 40.05Gy in 2.67Gy (15fx) and ultra-hypofractionation with 26Gy in 5.2Gy (5fx). The EARs (absolute additional cases of disease per 10,000 patient-years) for secondary malignancies in the lung, contralateral breast, esophagus, liver, thyroid, spinal cord, bones and soft tissue were calculated using a fraction-dependent dose-response model., Results: Based on risk modulation, (ultra-)hypofractionation resulted in significantly lower EARs for lung cancer (LC), contralateral breast cancer (CBC) and soft tissue sarcoma (STS) (p < .001). For the ultra-hypofractionated dose concept the median EARs for LC, CBC and STS were 42.8 %, 39.4 % and 58.1 % lower compared to conventional fractionation and 31.2 %, 25.7 % and 20.3 % compared to hypofractionation. The influence of fractionation on the risk of secondary malignancies for LC and CBC was less pronounced with 3D-CRT than with VMAT. For STS, however, the influence of fractionation was greater with 3D-CRT than with VMAT., Conclusion: Based on this simulation study (ultra-)hypofractionated postoperative breast cancer irradiation may be associated with a lower risk of secondary malignancies compared to a 5-week schedule., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Studies suggest that up to 70% of chronic obstructive pulmonary disease (COPD) cases globally are undiagnosed worldwide. Some of these undiagnosed patients may present with severe exacerbation and factors associated with underdiagnosis in this population are unknown. We investigated the key factors associated with underdiagnosis in two cohorts of patients hospitalised for severe COPD exacerbation at different time points., Methods: This retrospective, multicentre study analysed data from patients hospitalised for COPD exacerbation at two independent centres during two distinct time periods: between 1 January 2017 and 31 December 2018 in the Aquitaine region and between 1 January and 31 December 2022 in Paris. Undiagnosed COPD was defined as the absence of pulmonary function testing before the index exacerbation. Multivariate logistic regression was used to evaluate associations between underdiagnosis and patient characteristics., Results: Among the 424 patients, 93 (21.9%) were undiagnosed before hospitalisation, with a stable rate over time (22% in 2017-2018 and 21% in 2022). Multivariate analysis revealed that underdiagnosis was related to higher forced expiratory volume in one second (FEV 1 ; adjusted OR (aOR)=1.02, p=0.043) and female sex (aOR=1.91, p=0.015). Patients with undiagnosed COPD had significantly lower rehospitalisation and mortality rates. After the initial severe exacerbation, higher mortality was associated with a higher Charlson Comorbidity Index (HR=1.24, p=0.007) and older age (HR=1.05, p=0.008)., Conclusion: This retrospective, multicentre study demonstrated that about 20% of patients admitted with severe exacerbation were undiagnosed for COPD. Higher FEV 1 and female sex were associated with underdiagnosis, emphasising the need for special attention to this population. These findings highlight the need to improve training and access to spirometry and develop new diagnostic tools that facilitate earlier detection and management of COPD., Competing Interests: Competing interests: MG, EK, GV and LP have no conflicts of interest to disclose. CN-E reports grants and personal fees from GSK, Sanofi, AstraZeneca, Chiesi, ALK and Menarini outside the submitted work. JM has no conflicts of interest to declare. LG has no conflict of interest to declare related to the present work. He received grants from AADAIRC. He received speaker or advisory board fees from GSK, Asten, Air Liquide Medical System, Sanofi Genzyme, SOS Oxygène, AstraZeneca, ASV, Boehringer, VIVISOL and ResMed and support for attending the meeting from SOS Oxygène, Alize Santé and Asten. TS reports personal fees from Menarini, Sanofi, Chiesi, AstraZeneca, GSK outside the submitted work. MZ reports grants and personal fees from Menarini, personal fees from Sanofi, personal fees from Chiesi, personal fees from AstraZeneca, personal fees from CSL Behring and personal fees from GSK outside the submitted work, grants from AVAD, grants from FRM., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Enterovirus D68 (EV-D68) is associated with severe respiratory disease and acute flaccid myelitis (AFM). The 2022 outbreaks showed increased viral circulation and hospital admissions, but the expected rise in AFM cases did not occur. We analyzed EV-D68 genomes and infection outcomes from 2022 (a year without a national increase in AFM cases) and 2018 (a year with a national surge in AFM cases) to understand how viral genomic changes might influence disease outcomes., Methods: Residual respiratory samples that tested positive for rhinovirus/enterovirus at the Johns Hopkins Health System between 2018 and 2022 were collected for EV-D68 polymerase chain reaction, genotyping, and whole genome sequencing. Clinical and metadata were collected in bulk from the electronic medical records., Results: A total of 351 EV-D68 cases were identified, with most cases in children aged <5 years. Infections in 2018 were associated with higher odds of hospital admissions and intensive care unit care. Of 272 EV-D68 genomes, subclades B3 and A2/D1 were identified with B3 predominance (95.2%). A comparative analysis of the 2018 and 2022 whole genomes identified a cluster of amino acids (554D, 650T, 918T, 945N, 1445I, 1943I) that was associated with higher odds of severe outcomes., Conclusions: Our results show significant differences in the clinical outcomes of EV-D68 infections in 2018 and 2022 and highlight a 2018 cluster of genomic changes associated with these differences. Seasonal viral genomic surveillance-with in vitro characterization of the significance of these changes to viral fitness, immune responses, and neuropathogenesis-should shed light on the viral determinants of AFM., Competing Interests: Potential conflicts of interest. H. H. M. collaborates for research with Hologic and Diasorin. H. H. M. received honoraria from Roche Diagnostics and BD Diagnostics and serves on the advisory board of Seegene. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

According to current recommendations, older AML patients in first complete remission (CR) after induction chemotherapy should receive consolidation with intermediate-dose cytarabine (IDAC). However, no study has demonstrated the superiority of IDAC over other regimen. In this retrospective study, we compared the efficacy of mini-consolidations (idarubicin 8 mg/m 2 day 1, cytarabine 50 mg/m 2 /12 h, day 1-5) and IDAC. Inclusion criteria were newly diagnosed AML, age > 60 years, first CR after induction and at least 1 cycle of consolidation. Of the 796 included patients, 322 patients received mini-consolidations and 474 patients received IDAC. Mini-consolidation patients were older, and more often, they had de novo AML and unfavorable risk. The rate of allogeneic transplantation was higher in the IDAC group. The median number of cycles was higher in the mini-consolidation group (4 vs. 2; p < .0001). Median relapse-free survival was 18 months with mini-consolidations and 12 months with IDAC (p = .0064). In multivariate analysis, the risk of relapse or death was significantly higher in the IDAC group (p = .004). Median OS was 36 versus 31 months with mini-consolidations or IDAC, respectively (p = .46). In multivariate analysis, the consolidation regimen had no significant influence on OS (p = .43). In older AML patients, post-remission therapy with mini-consolidations represents an alternative to IDAC., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

The immunosuppressive nature of the tumor microenvironment poses a significant challenge to effective immunotherapies against glioblastoma (GB). Boosting the immune response is critical for successful therapy. Here, we adopted a cancer gene therapy approach to induce T-cell-mediated killing of the tumor through increased activation of the immune system. Patient-based three-dimensional (3D) GB models were infected with a replication-deficient adenovirus (AdV) armed with the class II major histocompatibility complex (MHC-II) transactivator (CIITA) gene (Ad-CIITA). Successful induction of surface MHC-II was achieved in infected GB cell lines and primary human GB organoids. Infection with an AdV carrying a mutant form of CIITA with a single amino acid substitution resulted in cytoplasmic accumulation of CIITA without subsequent MHC-II expression. Co-culture of infected tumor cells with either peripheral blood mononuclear cells (PBMCs) or isolated T-cells led to dramatic breakdown of GB organoids. Intriguingly, both wild-type and mutant Ad-CIITA, but not unarmed AdV, triggered immune-mediated tumor cell death in the co-culture system, suggesting an at least partially MHC-II-independent process. We further show that the observed cancer cell killing requires the presence of either CD8 + or CD4 + T-cells and direct contact between GB and immune cells. We did not, however, detect evidence of activation of canonical T-cell-mediated cell death pathways. Although the precise mechanism remains to be determined, these findings highlight the potential of AdV-mediated CIITA delivery to enhance T-cell-mediated immunity against GB., (© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Purpose: To analyze complications and potential risk factors associated with immediate prepectoral direct-to-implant breast reconstruction (DTIBR)., Methods: 295 patients (326 operated breasts) with DTIBR between March 2021 and December 2023 were included in this prospective study. Postoperative complications (postoperative bleeding, seroma, infection, necrosis, wound dehiscence, implant exchange/loss) were analyzed for potential risk factors by descriptive and logistic regression analyses., Results: The implant was covered by TiLOOP® Bra Pocket in 227 breasts (69.6%), by "dual-plane" technique in 20 breasts (6.1%), by acellular dermal matrix (ADM) in 1 breast (0.3%). No additional support was used for 78 breasts (23.9%). The use of mesh did not increase the risk for complications. Major complications requiring surgical revision occurred due to postoperative bleeding in 22 (6.7%), seroma in 2 (0.6%), infection in 13 (4.0%), necrosis in 10 (3.1%), and wound dehiscence in 10 (3.1%) breasts. Thirteen (4.0%) implants were exchanged, and 5 (1.5%) were explanted without substitution. One patient had to switch to autologous reconstruction due to skin necrosis. The main reasons for the removal/exchange of implants were infections (11 breasts, 3.4%) and necrosis (4 breasts, 1.2%). The risk for necrosis, infection, and wound dehiscence was mainly associated with the type of incision, especially skin-reducing incisions, and body mass index (BMI) ≥ 30 kg/m 2 ., Conclusion: Severe complications occurred primarily in patients with a BMI ≥ 30 kg/m 2 and when skin-reducing surgical techniques were performed., Trial Registry: This study was retrospectively registered at the German Clinical Trials Register (DRKS) on 20.06.2024., Drks-Id: DRKS00034493. https://drks.de/search/de/trial/DRKS00034493 ., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Health disparities in the Military Health System (MHS) have been consistently documented despite the system ensuring equal access to care for its beneficiaries. Research has shown that social, economic, and political factors (i.e., Social Determinants of Health) and health care-specific factors like provider bias and systemic discrimination are key drivers of health disparities in the general population. Medical education focused on introducing these concepts using case-based learning has led to effective learning of health equity terminology. However, a significant gap exists in identifying optimal teaching approaches to develop skills to recognize these factors in actual clinical cases. This begs the million-dollar question: can case-based learning help trainees acquire the skills needed to identify the main factors contributing to health disparities in the MHS?, Materials and Methods: A longitudinal case-based curriculum was developed in which clinical cases from the Internal Medicine Wards, Medical Intensive Care Unit, or General Internal Medicine Clinic at the National Capital Consortium were solicited from trainees and analyzed for evidence of health care provider bias and systemic forms of discrimination using small groups. The National Capital Consortium Internal Medicine Residency Program implemented this pilot study in November 2021. A retrospective pretest-posttest survey assessing trainee reactions to the curriculum and changes in self-reported confidence in skills was used for curriculum assessment. Survey data were analyzed using a paired samples t-test., Results: The survey was administered during the last session of the 2022-2023 academic year, with 14 of the 23 available trainees completing it: a 60.8% response rate. Overall, 93% reported that the cases selected that academic year were engaging; the skills they were taught were practice-changing, and the educational value of the curriculum was good, very good, or excellent. Confidence ratings, assessed via a 5-point Likert Scale, demonstrated a statistically significant increase in self-reported confidence in the following skill domains with large effect sizes: identification of bias and systemic discrimination in clinical cases-change in mean: 1.07 (Pre: 3.29, Post: 4.36), P < .001, g = 1.38; recognizing and mitigating personal biases-change in mean: 0.71 (Pre: 3.50, Post: 4.21), P <.001, g = 1.10; participating in a discussion about health care provider bias and systemic discrimination-change in mean: 0.79 (Pre: 3.57, Post: 4.36), P  = .001, g = 1.06; and leading a discussion about bias and systemic discrimination-change in mean: 1.00 (Pre: 2.93, Post: 3.93), P = .002, g = 0.98., Conclusions: As the need to address health disparities in the United States becomes more pressing, so does the need for military physicians to recognize the drivers of these disparities within the MHS. Results from this pilot study of Health Equity Rounds suggest that case-based learning may be an optimal teaching approach to improve the skills of military Internal Medicine trainees in identifying and recognizing the impact of health care provider bias and systemic discrimination on clinical cases from the MHS., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Control over the lateral dimensions of colloidal nanostructures is a complex task which requires a deep understanding of the formation mechanism and reactivity in the corresponding systems. As a result, it provides a well-founded insight to the physical and chemical properties of these materials. In this work, the preparation of quasi-2D methylammonium lead bromide nanostripes and discuss the influence of some specific parameters on the morphology and stability of this material is demonstrated. The variation in the amount of the main ligand dodecylamine gives a large range of structures beginning with 3D brick-like particles at low concentrations, nanostripes at elevated and ultimately nanosheets at large concentrations. The amount of the co-ligand trioctylphosphine can alter the width of the nanostripe shape to a certain degree. The thickness can be adjusted by the amount of the second precursor methylammonium bromide. Additionally, insights are given for the suggested formation mechanism of these anisotropic structures as well as for stability against moisture at ambient conditions in comparison with differently synthesized nanosheet samples., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Background: The prognosis for patients with central nervous system (CNS) retinoblastoma (RB) (trilateral or stage 4b metastatic RB) treated with high-dose chemotherapy and autologous stem cell transplant (HDC-ASCT) remains poor. The impact of irradiation when administered as part of upfront therapy post HDC-ASCT on treatment outcomes and survival is unknown., Methods: We performed a retrospective review of all patients with CNS RB (seven stage 4b, eight trilateral, one pineal lesion belonging to methylation group RB) who underwent induction chemotherapy with an intent to proceed to HDC-ASCT at two institutions., Results: Twelve of 16 patients (n = 75%) achieved an objective response to induction chemotherapy, while four patients had progressive/refractory disease; two patients responded to subsequent therapy and proceeded to ASCT, and two patients did not. Seven of 14 patients who underwent HDC-ASCT, received radiotherapy as part of upfront therapy post HDC-ASCT in the form of craniospinal irradiation (CSI) (n = 3), intraventricular radioimmunotherapy (n = 3), or both CSI and intraventricular radioimmunotherapy (n = 1). The Kaplan-Meier estimate of overall survival for these patients was 62.5% at 5 years; no patients developed second malignant neoplasms within the radiation fields. For the seven patients who did not receive radiotherapy, the overall survival was 28.6% at 5 years., Conclusions: CSI (23.4 Gy) alone or in conjunction with intraventricular RIT may have clinical utility in eliminating persistent MRD post HDC-ASCT, contributing to improved disease-free survival in patients with CNS RB. This treatment strategy merits evaluation in a prospective, multicenter clinical trial for patients with CNS metastatic RB., (© 2024 Wiley Periodicals LLC.)

Introduction: While the ethical significance of caregivers in neurological research has increasingly been recognized, the role of caregivers in brain-computer interface (BCI) research has received relatively less attention., Objectives: This report investigates the extent to which caregivers are mentioned in publications describing implantable BCI (iBCI) research for individuals with motor dysfunction, communication impairment, and blindness., Methods: The scoping review was conducted in June 2024 using the PubMed and Web of Science bibliographic databases. The articles were systematically searched using query terms for caregivers, family members, and guardians, and the results were quantitatively and qualitatively analyzed., Results: Our search yielded 315 unique studies, 78 of which were included in this scoping review. Thirty-four (43.6%) of the 78 articles mentioned the study participant's caregivers. We sorted these into 5 categories: Twenty-two (64.7%) of the 34 articles thanked caregivers in the acknowledgement section, 6 (17.6%) articles described the caregiver's role with regard to the consent process, 12 (35.3%) described the caregiver's role in the technical maintenance and upkeep of the BCI system or in other procedural aspects of the study, 9 (26.5%) discussed how the BCI enhanced participant communication and goal-directed behavior with the help of a caregiver, and 3 (8.8%) articles included general comments that did not fit into the other categories but still related to the importance of caregivers in the lives of the research participants., Discussion: Caregivers were mentioned in less than half of BCI studies in this review. The studies that offered more robust discussions of caregivers provide valuable insight into the integral role that caregivers play in supporting the study participants and the research process. Attention to the role of caregivers in successful BCI research studies can help guide the responsible development of future BCI study protocols., 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 Wohns, Dorfman and Klein.)

Background: Childhood vaccinations can reduce disease burden and associated antibiotic use, in turn reducing the risk of antimicrobial resistance (AMR). We retrospectively estimated the population-level reductions in antibiotic use in India following the introduction of vaccines against Streptococcus pneumoniae and Haemophilius influenzae type B in the national immunization program for children in the mid-2010s and projected future gains to 2028 if vaccination coverage were to be increased., Methods: Using IndiaSim, a dynamic agent-based microsimulation model (ABM) for India, we simulated the spread of Streptococcus pneumoniae and Haemophilius influenzae type B (Hib) among children to estimate reductions in antibiotic use under the scenarios of: (i) pneumococcal and Hib vaccine coverage levels equivalent to the national coverage of pentavalent diphtheria-pertussis-tetanus third dose (DPT3) compared to a baseline of no vaccination, and (ii) near-universal (90%) coverage of the vaccines compared to pre-COVID national DPT3-level coverage. Model parameters, including national DPT3 coverage rates, were based on data from the National Family Household Survey 2015-2016 and other published sources. We quantified reductions in antibiotic consumption nationally and by state and wealth quintiles., Findings: We estimate that coverage of S. pneumoniae and Hib vaccines at the same level as DPT3 in India would translate to a 61.4% [95% UI: 43.8-69.5] reduction in attributable antibiotic use compared to a baseline of zero vaccination coverage. Increases in childhood vaccination coverage between 2004 and 2016 have likely reduced attributable antibiotic demand by as much as 93.4% among the poorest quintile. Increasing vaccination coverage by an additional 11 percentage points from 2016 levels results in mortality and antibiotic use across wealth quintiles becoming increasingly similar (p < 0.05), reducing in health inquities. We project that near-universal vaccine coverage would further reduce inequities in antibiotic demand and may eliminate of outbreak-associated antibiotic use from S. pneumoniae and Hib., Interpretation: Though vaccination has a complex relationship with antibiotic use because both are modulated by socioeconomic factors, increasing vaccinations for S. pneumoniae and Hib may have a significant impact on reducing antibiotic use and improving health outcomes among the poorest individuals., Funding: The Bill & Melinda Gates Foundation (grant numbers OPP1158136 and OPP1190803)., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Objective: Activation of type I interferon (IFN) response has been shown to correlate with disease activity in systemic sclerosis (SSc). It is currently unknown whether the tissue-specific type I IFN activation is a consequence of the response observed in blood or rather its source. Exosomes from SSc fibroblasts were recently shown to activate macrophages in vitro. Here, we aimed to determine the source of type I IFN signature in SSc skin biopsies and the potential role of exosomes from SSc dermal fibroblasts in the process., Methods: Skin biopsies were obtained from the forearms of healthy patients and of those with SSc and processed for dermal fibroblasts and keratinocytes. Exosomes were isolated from healthy and SSc dermal fibroblast supernatants by ultracentrifugation and added to human skin keratinocytes. Keratinocyte transcriptome was analyzed by RNA sequencing (RNA-seq) analysis. TANK-binding kinase (TBK) and JAK were inhibited using a small molecule inhibitor (GSK8612) and tofacitinib, respectively., Results: SSc skin biopsies showed the highest levels of type I IFN response in the epidermal layer. RNA-seq analysis of keratinocytes transcriptome following exposure to dermal fibroblast exosomes showed strong up-regulation of IFN signature genes induced by SSc exosomes compared to healthy control. Inhibition of TBK or JAK activity suppressed the up-regulation of the IFN signature induced by SSc exosomes., Conclusion: IFN activation of SSc keratinocytes is dependent on their crosstalk with dermal fibroblasts and inducible by extracellular exosomes. Our data indicate that SSc fibroblast exosomes contribute to the type I IFN activation in SSc skin through activation of pattern recognition receptors upstream of TBK., (© 2024 The Author(s). Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

The COVID-19 pandemic highlighted the need for robust epidemic forecasts, projecting health burden over short- and medium-term time horizons. Many COVID-19 forecasting models incorporate information on infection transmission, disease progression, and the effects of interventions, but few combine information on how individuals change their behavior based on altruism, fear, risk perception, or personal economic circumstances. Moreover, early models of COVID-19 produced under- and over-estimates, failing to consider the complexity of human responses to disease threat and prevention measures. In this study, we modeled adaptive behavior during the first year of the COVID-19 pandemic in Maryland, USA. The adapted compartmental model incorporates time-varying transmissibility informed on data of environmental factors (e.g., absolute humidity) and behavioral factors (aggregate mobility and perceived risk). We show that humidity and mobility alone did little to explain transmissibility after the first 100 days. Including adaptive behavior in the form of perceived risk as a function of hospitalizations more effectively explained inferred transmissibility and improved out-of-sample fit, demonstrating the model's potential in real-time forecasting. These results demonstrate the importance of incorporating endogenous behavior in models, particularly during a pandemic, to produce more accurate projections, which could lead to more impactful and efficient decision making and resource allocation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eili Klein reports financial support was provided by Centers for Disease Control and Prevention. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Influenza, a human disease caused by viruses in the Orthomyxoviridae family, is estimated to infect 5% -10 % of adults and 20% -30 % of children annually. Influenza A (IAV) and Influenza B (IBV) viruses accumulate amino acid substitutions (AAS) in the hemagglutinin (HA) and neuraminidase (NA) proteins seasonally. These changes, as well as the dominating viral subtypes, vary depending on geographical location, which may impact disease prevalence and the severity of the season. Genomic surveillance is crucial for capturing circulation patterns and characterizing AAS that may affect disease outcomes, vaccine efficacy, or antiviral drug activities. In this study, whole-genome sequencing of IAV and IBV was attempted on positive remnant clinical samples (587) collected from 580 patients between June 2023 and February 2024 in the Johns Hopkins Health System (JHHS). Full-length HA segments were obtained from 424 (72.2 %) samples. H1N1pdm09 (71.7 %) was the predominant IAV subtype, followed by H3N2 (16.7 %) and IBV-Victoria clade V1A.3a.2 (11.6 %). Within H1N1pdm09 HA sequences, the 6B1A.5a.2a.1 (60.5 %) clade was the most represented. Full-length NA segments were obtained from 421 (71.7 %) samples. Within H1N1pdm09 and IBV, AAS previously proposed to change susceptibility to NA inhibitors were infrequently detected. Phylogeny of HA and NA demonstrated heterogeneous HA and NA H1N1pdm09 and IBV subclades. No significant differences were observed in admission rates or use of supplemental oxygen between different subtypes or clades. Influenza virus genomic surveillance is essential for understanding the seasonal evolution of influenza viruses and their association with disease prevalence and outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HHM reports research collaborations with Bio-Rad, Qiagen, DiaSorin, and Hologic, received honoraria from BD diagnostics and Bio-Rad, and serves on the advisory board for Seegene., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background:  Metabolic syndrome (MetS) is a collection of risk factors, including hypertension, high fasting blood glucose, high fasting triglyceride and low high-density lipoprotein (HDL) cholesterol levels that may increase the risk for cardiovascular disease and type 2 diabetes. The study aimed to determine the prevalence of MetS among adults attending a Free State district hospital's outpatient department., Methods:  A cross-sectional study included a consecutive sample of consenting patients 18 years and older from 18 October 2021 to 19 November 2021. Patients' waist circumference was measured, and data were extracted from patients' files., Results:  The 409 participants were predominantly females (64.2%). The median age was 60 years. Triglyceride and HDL cholesterol levels were available for 27.4% and 26.9% of patients, respectively. Of the 278 (68.0%) patients with sufficient information to determine their MetS status, 187 (67.3%) had MetS. Of the males with sufficient information, 49.1% (n = 56/114) had MetS compared to 79.9% (n = 131/164) of the females with sufficient information (p  0.001). The age group 60-79 years had the highest prevalence (76.7%, p  0.001). In all race groups, at least two-thirds of patients had MetS (p = 0.831)., Conclusion:  Incomplete patient notes and failure to do investigations led to a third of patients not having sufficient information to determine their MetS status. In patients with sufficient information, a high prevalence of MetS was found.Contribution: This study highlights the challenges of determining MetS retrospectively in an outpatient population and the need for completeness of medical note keeping and routine investigations in high-risk patients. It also notes the high prevalence of MetS.

One of the main signs we do not know enough about arrhythmogenic right ventricular dysplasia 9/cardiomyopathy (ARVCD9, OMIM #609040, autosomal dominant) is the lack of early markers and therapeutic alternatives. To better study disease pathways in vitro, we generated human induced pluripotent stem cell (hiPSC) lines from the father (UKJi006-A) and son (UKJi001-A), who both shared the same heterozygous mutation in the PKP2 gene (OMIM *602861). While the father had a clinical diagnosis of ARVC, the son lacked the ARVC phenotype. To generate hiPSC lines, non-integrating Sendai virus (SeV) vectors expressing the reprogramming factors (OCT4, SOX2, KLF4, and c-MYC) were used for reprogramming patient peripheral blood mononuclear cells (PBMCs)., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Rotavirus is a leading cause of diarrhea in infants and young children in many low- and middle-income countries. India launched a childhood immunization program for rotavirus in 2016, starting with four states and expanding it to cover all states by 2019. The objective of this study was to estimate the effects of the rotavirus vaccination program in India on disease burden and antibiotic misuse., Methods: We built a dynamic agent-based model of rotavirus progression in children under five within each district in India. Simulations were run for various scenarios of vaccination coverage in the context of India's Universal Immunization Programme. Population data were obtained from the National Family Household Surveys and used to calibrate the models. Disease parameters were obtained from published studies. We estimated past and projected future reduction of disease burden and antibiotic misuse due to full vaccination nationwide, by state, and by wealth quintile., Results: We estimate that rotavirus vaccination in India has reduced the prevalence of rotavirus cases by 33.7% (prediction interval: 30.7-36.0%), total antibiotic misuse due to rotavirus by 21.8% (18.6-25.1%), and total deaths due to rotavirus by 38.3% (31.3-44.4%) for children under five. We estimate total antibiotic misuse due to rotavirus infection to be 7.6% (7.5-7.9%) of total antibiotic consumption in this demographic versus 9.6% (9.4-9.9%) in the absence of vaccination. We project rotaviral prevalence to drop to below one case for every 100,000 individuals in those below five if vaccination coverage is increased by 50.3% (45.2-58.5%) to 68.1% (63.1-76.4) nationwide., Conclusion: Universal coverage of childhood rotavirus vaccination can substantially reduce inappropriate antibiotic use in India., Competing Interests: Declaration of competing interest All authors declare no financial or non-financial competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In the United States, 2.0 million new cancer cases and around 600,000 cancer deaths are estimated to occur in 2024. Early detection gives cancer patients the best chance for treatment success. Currently, cancer screening in the general population is recommended for a limited set of cancers; as a result, most cancer types are not regularly screened. Thus, in recent years, we have seen a wave of novel, non-invasive, single- and multi-cancer detection tests (SCD and MCD), promising detection of cancer signals prior to the onset of symptoms and/or clinical diagnosis. To accelerate the development, access, and adoption of these tests, the Blood Profiling Atlas in Cancer (BLOODPAC) Consortium, a collaborative infrastructure for developing standards and best practices, established the Early Detection & Screening (ED&S) Working Group. The early detection space is in need of consensus around definitions for SCD and MCD tests that harmonize terminology across diverse stakeholders, thereby reducing communication barriers and ultimately advancing the discipline. To this end, the ED&S Working Group compiled a lexicon of terms, chosen based on perceived importance, frequency of use, lack of clarity, and unique challenges in the context of SCD and MCD tests. This lexicon was submitted to the FDA for their feedback, which was incorporated. In this work, we present the first installment of the lexicon, consisting of 14 primary terms, that will be part of an online dictionary and provide a foundation for future projects of BLOODPAC's ED&S Working Group., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Aims: To evaluate the ability of logistic regression and machine learning methods to predict active arterial extravasation on computed tomographic angiography (CTA) in patients with acute gastrointestinal hemorrhage using clinical variables obtained prior to image acquisition., Materials and Methods: CT angiograms performed for the indication of gastrointestinal bleeding at a single institution were labeled retrospectively for the presence of arterial extravasation. Positive and negative cases were matched for age, gender, time period, and site using Propensity Score Matching. Clinical variables were collected including recent history of gastrointestinal bleeding, comorbidities, laboratory values, and vitals. Data were partitioned into training and testing datasets based on the hospital site. Logistic regression, XGBoost, Random Forest, and Support Vector Machine classifiers were trained and five-fold internal cross-validation was performed. The models were validated and evaluated with the area under the receiver operating characteristic curve., Results: Two-hundred and thirty-one CTA studies with arterial gastrointestinal extravasation were 1:1 matched with 231 negative studies (N=462). After data preprocessing, 389 patients and 36 features were included in model development and analysis. Two hundred and fifty-five patients (65.6%) were selected for the training dataset. Validation was performed on the remaining 134 patients (34.4%); the area under the receiver operating characteristic curve for the logistic regression, XGBoost, Random Forest, and Support Vector Machine classifiers was 0.82, 0.68, 0.54, and 0.78, respectively., Conclusion: Logistic regression and machine learning models can accurately predict presence of active arterial extravasation on CTA in patients with acute gastrointestinal bleeding using clinical variables., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Purpose: To assess multicenter two-year patency outcomes of endovascular arteriovenous fistulas (endoAVF) created with the WavelinQ device., Materials and Methods: Patients who had fistulas created at three centers from January 2018 to December 2020 were included in this retrospective study. In total, 112 patients underwent endoAVF creation [40 females, 72 males; mean age 60 years (range 18-88)]. Data collected included patient demographics, location of fistula creation, interventions performed, and brachial artery flows pre- and post-creation. Two-year cumulative patency, functional patency, and primary patency were assessed with Kaplan-Meier methodology. Factors affecting patency and maturation were examined using the Cox proportional hazards model., Results: Technical success defined as angiographically successful endoAVF creation was 97.3% (109/112). In 11 patients the fistula did not mature for dialysis use. For 98 patients (87%) with endoAVF maturation, 12- and 24-month cumulative patency was 94.3% and 91.7%. Functional patency (two-needle cannulation) at 12 and 24 months was 95.7% and 92.7%, respectively. Median maturation time is 95 days (IQR 51-231 days). Male gender and brachial vein coiling at the time of endoAVF creation were predictive of maturation. There were 34 censored events (four patients undergoing renal transplantation; 30 patients deceased). Number of reinterventions per patient year was 0.73 where 43 were maturation procedures and 101 were maintenance procedures. One Grade 3 complication occurred of arterial access puncture site pseudoaneurysm., Conclusion: A high two-year functional and cumulative patency following endoAVF creation with the WavelinQ device was observed in this multicenter real-world experience Level of Evidence: 3 Level of Evidence III., (© 2024. The Author(s).)

Purpose: To report the prospective long-term outcome data of patients whose chemotherapy decision was guided by the EndoPredict test., Methods: Patients with hormone receptor-positive HER2-negative early breast cancer with 0-3 positive lymph nodes were enrolled. The EndoPredict test was carried out on all tumor samples. Treatment compliance, local recurrence, distant metastases, and survival were evaluated. Associations of EPclin risk stratification with 5-year disease-free survival and distant metastasis-free survival were evaluated by time-to-event analysis., Results: 368 consecutive patients were included in the analysis. Median follow-up was 8.2 years. EndoPredict allocated 238 (65%) in the low-risk and 130 (35%) patients in the high-risk group. Risk for disease recurrence or death in EPclin high-risk patients was twofold higher than in EPclin low-risk patients (hazard ratio [HR] 2.08; 95% CI 1.26-3.44; p = 0.004). EPclin low-risk patients had a 5-year disease-free survival of 95.3% (95% CI 92.6-98.0%). EPclin high-risk patients were at higher risk of developing distant metastases or death (HR 2.21; 95% CI 1.27-3.88; p = 0.005). EPclin high-risk patients who underwent chemotherapy had a 5-year DFS of 89.1% (95% CI 82.7-96.1%) in contrast to high-risk patients without chemotherapy (68.9%; 95% CI 56.2-84.5%; HR 0.46; 95% CI 0.23-0.95; p = 0.036). EPclin high-risk patients were at higher risk of experiencing distant metastases or death than EPclin low-risk patients regardless of menopausal status (premenopausal: HR 3.55; 95% CI 1.17-12.32; p = 0.025; postmenopausal: HR 1.92; 95% CI 0.99-3.7; p = 0.054)., Conclusion: EndoPredict can guide decisions on adjuvant chemotherapy in early luminal breast cancer. EndoPredict risk stratification is also applicable in premenopausal women., (© 2024. The Author(s).)

Study Objective: Inappropriate antibiotic prescribing for acute respiratory tract infections is a common source of low-value care in the emergency department (ED). Racial and socioeconomic disparities have been noted in episodes of low-value care, particularly in children. We evaluated whether prescribing rates for acute respiratory tract infections when antibiotics would be inappropriate by guidelines differed by race and socioeconomics., Methods: A retrospective cross-sectional analysis of adult and pediatric patient encounters in the emergency department (ED) between 2015 and 2023 at 5 hospitals for acute respiratory tract infections that did not require antibiotics by guidelines. Multivariable regression was used to calculate the risk ratio between race, ethnicity, and area deprivation index and inappropriate antibiotic prescribing, controlling for patient age, sex, and relevant comorbidities., Results: A total of 147,401 ED encounters (55% pediatric, 45% adult) were included. At arrival, 4% patients identified as Asian, 50% as Black, 5% as Hispanic, and 23% as White. Inappropriate prescribing was noted in 7.6% of overall encounters, 8% for Asian patients, 6% for Black patients, 5% for Hispanic patients, and 12% for White patients. After adjusting for age, sex, comorbidities, and area deprivation index, White patients had a 1.32 (95% confidence interval, 1.26 to 1.38) higher likelihood of receiving a prescription compared with Black patients. Patients residing in areas of greater socioeconomic deprivation, regardless of race and ethnicity, had a 0.74 (95% confidence interval, 0.70 to 0.78) lower likelihood of receiving a prescription., Conclusion: Our results suggest that although overall inappropriate prescribing was relatively low, White patients and patients from wealthier areas were more likely to receive an inappropriate antibiotic prescription., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Young adults who are sexual and gender minorities (SGM) are at the highest risk for tobacco initiation in young adulthood. Minority stress theory suggests that sexual orientation and gender identity (SOGI)-based discrimination may contribute to nicotine and tobacco use disparities. Our study aimed to quantify the association between SOGI-based distal minority stressors and current tobacco use among SGM young adults living in the United States (US)., Methods: Eligible participants-including young adults (aged 18-35 years old), who identified as SGM, and were currently residing in the US (N=1116) -were recruited via Prolific into an online survey. We applied stepwise binary regressions with backward selection to model the association between average past 30-day distal minority stress and current tobacco use (i.e., combustible cigarettes or e-cigarettes), controlling for perceived stress and sociodemographic covariates. We also tested interactions between minority stress and SGM status. Exploratory analyses assessed associations between minority stress and current tobacco use among YA, stratified by SGM subgroup., Results: A 1-unit increase in experiencing minority stress in the past 30-days was associated with 1.02 greater odds of current tobacco use among SGM young adults. No difference between SGM subgroups in this association was found. Examining stratified SGM subgroups, a 1-unit increase in minority stress was associated with 1.11 greater odds of current tobacco among transgender adults only., Conclusion: Distal minority stress is differentially associated with current tobacco use for transgender young adults, which suggests that tobacco prevention and cessation interventions may need tailoring for subgroups., Implications: This study details the influence of minority stress on current tobacco use among sexual and gender minority (SGM) young adults. Findings underscore the need for targeted and tailored approaches to tobacco control, wherein SGM young adults most at-risk are engaged in cessation interventions that address minority stress as a contributing factor to tobacco use and which support their resilience. To promote health equity, tobacco control must address the contexts that engender minority stress. Assessment of policy impacts on SGM tobacco use and the effectiveness of interventions disseminated within SGM-supportive and discriminatory policy environments are important next steps., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joanne G. Patterson reports financial support was provided by National Cancer Institute of the National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: The identification of internal mammary lymph node metastases and the assessment of associated risk factors are crucial for adjuvant regional lymph node irradiation in patients with breast cancer. The current study aims to investigate whether tumor contact with internal mammary perforator vessels is associated with gross internal mammary lymph node involvement., Methods and Materials: We included 297 patients with primary breast cancer and gross internal mammary (IMN+) and/or axillary metastases as well as 230 patients without lymph node metastases. Based on pretreatment dynamic contrast-enhanced magnetic resonance imaging, we assessed contact of the tumor with the internal mammary perforating vessels (IMPV)., Results: A total of 59 patients had ipsilateral IMN+ (iIMN+), 10 patients had contralateral IMN+ (cIMN+), and 228 patients had ipsilateral axillary metastases without IMN; 230 patients had node-negative breast cancer. In patients with iIMN+, 100% of tumors had contact with ipsilateral IMPV, with 94.9% (n = 56) classified as major contact. In iIMN- patients, major IMPV contact was observed in only 25.3% (n = 116), and 36.2% (n = 166) had no IMPV contact at all. Receiver operating characteristic analysis revealed that "major IMPV contact" was more accurate in predicting iIMN+ (area under the curve, 0.85) compared with a multivariate model combining grade of differentiation, tumor site, size, and molecular subtype (area under the curve, 0.65). Strikingly, among patients with cIMN+, 100% of tumors had contact with a crossing contralateral IMPV, whereas in cIMN- patients, IMPVs to the contralateral side were observed in only 53.4% (iIMN+) and 24.8% (iIMN-), respectively., Conclusions: Tumor contact with the IMPV is highly associated with risk of gross IMN involvement. Further studies are warranted to investigate whether this identified risk factor is also associated with microscopic IMN involvement and whether it can assist in the selection of patients with breast cancer for irradiation of the internal mammary lymph nodes., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose of the Review: Intracranial neurostimulation is a well-established treatment of neurologic conditions such as drug-resistant epilepsy (DRE) and movement disorders, and there is emerging evidence for using deep brain stimulation to treat obsessive-compulsive disorder (OCD) and depression. Nearly all published reports of intracranial neurostimulation have focused on implanting a single device to treat a single condition. The purpose of this review was to educate neurology clinicians on the background literature informing dual treatment of 2 comorbid neuropsychiatric conditions epilepsy and OCD, discuss ethical and logistical challenges to dual neuropsychiatric treatment with a single device, and demonstrate the promise and pitfalls of this approach through discussion of the first-in-human closed-looped responsive neurostimulator (RNS) implanted to treat both DRE (on-label) and OCD (off-label)., Recent Findings: We report the first implantation of an intracranial closed-loop neurostimulation device (the RNS system) with the primary goal of treating DRE and a secondary exploratory goal of managing treatment-refractory OCD. The RNS system detects electrophysiologic activity and delivers electrical stimulation through 1 or 2 electrodes implanted into a patient's seizure-onset zones (SOZs). In this case report, we describe a patient with treatment-refractory epilepsy and OCD where the first lead was implanted in the right superior temporal gyrus to target the most active SOZ based on stereotactic EEG (sEEG) recordings and semiology. The second lead was implanted to target the right anterior peri-insular region (a secondary SOZ on sEEG) with the distal-most contacts in the right nucleus accumbens, a putative target for OCD neurostimulation treatment. The RNS system was programmed to detect and record the unique electrophysiologic signature of both the patient's seizures and compulsions and then deliver tailored electrical pulses to disrupt the pathologic circuitry., Summary: Dual treatment of refractory focal epilepsy and OCD with an intracranial closed-loop neurostimulation device is feasible, safe, and potentially effective. However, there are logistical challenges and ethical considerations to this novel approach to treatment, which require complex care coordination by a large multidisciplinary team., Competing Interests: The authors report no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2024 American Academy of Neurology.)

Crohn's disease (CD) is marked by recurring intestinal inflammation and tissue injury, often resulting in fibrostenosis and bowel obstruction, necessitating surgical intervention with high recurrence rates. To elucidate the mechanisms underlying fibrostenosis in CD, we analyzed the transcriptome of cells isolated from the transmural ileum of patients with CD, including a trio of lesions from each patient: non-affected, inflamed, and stenotic ileum samples, and compared them with samples from patients without CD. Our computational analysis revealed that profibrotic signals from a subset of monocyte-derived cells expressing CD150 induced a disease-specific fibroblast population, resulting in chronic inflammation and tissue fibrosis. The transcription factor TWIST1 was identified as a key modulator of fibroblast activation and extracellular matrix (ECM) deposition. Genetic and pharmacological inhibition of TWIST1 prevents fibroblast activation, reducing ECM production and collagen deposition. Our findings suggest that the myeloid-stromal axis may offer a promising therapeutic target to prevent fibrostenosis in CD.

Healthcare-associated infections (HAIs) due to multi-drug resistant organisms (MDROs) are a significant burden to the healthcare system. Patients are sometimes already infected at the time of admission to the hospital (referred to as "importation"), and additional patients might get infected in the hospital through transmission ("nosocomial infection"). Since many of these importation and nosocomial infection cases may present no symptoms (i.e., "asymptomatic"), rapidly identifying them is difficult since testing is limited and incurs significant delays. Although there has been a lot of work on examining the utility of both mathematical models of transmission and machine learning for identifying patients at risk of MDRO infections in recent years, these methods have limited performance and suffer from different drawbacks: Transmission modeling-based methods do not make full use of rich data contained in electronic health records (EHR), while machine learning-based methods typically lack information about mechanistic processes. In this work, we propose NEURABM, a new framework which integrates both neural networks and agent-based models (ABM) to combine the advantages of both modeling-based and machine learning-based methods. NEURABM simultaneously learns a neural network model for patient-level prediction of importation, as well as the ABM model which is used for identifying infections. Our results demonstrate that NEURABM identifies importation and nosocomial infection cases more accurately than existing methods.