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Background: The effectiveness of somatic neoantigen-based immunotherapy is often hindered by the limited number of mutations in tumors with low to moderate mutation burden. Focusing on microsatellite-stable colorectal cancer (CRC), this study investigates the potential of tumor-associated circular RNAs (circRNAs) as an alternative source of neoepitopes in CRC., Methods: Tumor-associated circRNAs in CRC were identified using the MiOncoCirc database and ribo-depletion RNA sequencing of paired clinical normal and tumor samples. Candidate circRNA expression was validated by quantitative real-time PCR (RT-qPCR) using divergent primers. TransCirc database was used for translation prediction. Human leukocyte antigen binding affinity of open reading frames from potentially translatable circRNA was predicted using pVACtools. Strong binders from messenger RNA-encoded proteins were excluded using BlastP. The immunogenicity of the candidate antigens was functionally validated through stimulation of naïve CD8 + T cells against the predicted neoepitopes and subsequent analysis of the T cells through enzyme-linked immunospot (ELISpot) assay, intracellular cytokine staining (ICS) and granzyme B (GZMB) reporter. The cytotoxicity of T cells trained with antigen peptides was further tested using patient-derived organoids., Results: We identified a neoepitope from circRAPGEF5 that is upregulated in CRC tumor samples from MiOncoCirc database, and two neoepitopes from circMYH9, which is upregulated across various tumor samples from our matched clinical samples. The translation potential of candidate peptides was supported by Clinical Proteomic Tumor Analysis Consortium database using PepQuery. The candidate peptides elicited antigen-specific T cells response and expansion, evidenced by various assays including ELISpot, ICS and GZMB reporter. Furthermore, T cells trained with circMYH9 peptides were able to specifically target and eliminate tumor-derived organoids but not match normal organoids. This observation underscores the potential of circRNAs as a source of immunogenic neoantigens. Lastly, circMYH9 was enriched in the liquid biopsies of patients with CRC, thus enabling a detection-to-vaccination treatment strategy for patients with CRC., Conclusions: Our findings underscore the feasibility of tumor-associated circRNAs as an alternative source of neoantigens for cancer vaccines targeting tumors with moderate mutation levels., Competing Interests: Competing interests: No, there are no competing interests., (© 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.)

The current standard treatment for muscularis propria-invasive (T2) colorectal cancer is surgical colectomy with lymph node dissection. With the advent of new endoscopic resection techniques, such as endoscopic full-thickness resection or endoscopic intermuscular dissection, T2 colorectal cancer, with metastasis to 20%-25% of the dissected lymph nodes, may be the next candidate for endoscopic resection following submucosal-invasive (T1) colorectal cancer. We present a novel endoscopic treatment strategy for T2 colorectal cancer and suggest further study to establish evidence on oncologic and endoscopic technical safety for its clinical implementation.

Dengue is a mosquito-transmitted infection endemic in tropical and subtropical locations of the world where nearly half of the world's population resides. The disease may present as mild febrile illness to severe and can even be fatal if untreated. There are four genetically related but antigenically distinct dengue virus (DENV) serotypes. Immune responses to DENV infection are in general protective but under certain conditions, they can also aggravate the disease. The importance of the cellular immune responses and the antibody responses involving IgG and IgM has been well-studied. In contrast, not much has been described on the potential role of hypersensitivity reactions involving IgE in dengue. Several studies have shown elevated levels of IgE in patients with dengue fever, but its involvement in the immune response against the virus and disease is unknown. Activation of mast cells (MCs) and basophils mediated through dengue-specific IgE could result in the release of mediators affecting dengue virus infection. The present review explores the relationships between the induction of IgE in dengue virus infection, and the potential role of MCs and basophils, exploring both protective and pathogenic aspects, including antibody-dependent enhancement (ADE) of infection in dengue.

Introduction: Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are significant contributors to the burden of acute respiratory infections in children, but data on hMPV from Southeast Asia are limited despite its potential for serious disease. This study aimed to compare the clinical presentation, resource utilisation and outcomes between hMPV and RSV infections in hospitalised Malaysian children., Methods: This retrospective, observational study included children aged ≤12 years old hospitalised with hMPV or RSV, confirmed via direct fluorescent antibody (DFA) methods, between 1 July to 30 October 2022 at Hospital Tuanku Ja'afar Seremban, Malaysia. Demographic, clinical presentation, resource utilisation and outcome data were analysed. Propensity score matching was used to balance cohorts based on key demographic and clinical characteristics., Results: This study included 192 patients, comprising 112 with hMPV and 80 with RSV. hMPV patients were older (median age 20.5 vs. 9.4 months, p < 0.001) and had a higher incidence of comorbidities (24.1% vs. 7.5%, p = 0.003). Fever was more common in the hMPV group (97.3% vs. 73.8%, p < 0.001), but the other clinical manifestations were similar. Postmatching analysis showed higher corticosteroid use in the hMPV group (p = 0.01). No significant differences were observed in the use of other resources, PICU admissions, duration of hospitalisation or mortality rates between both groups., Conclusion: hMPV and RSV infections in children share similar clinical manifestations and outcomes, with hMPV affecting older children and showing higher corticosteroid usage. These findings emphasise the need for equal clinical vigilance for both hMPV and RSV in paediatric respiratory infections., (© 2024 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Globally, colorectal cancer (CRC) is the third most frequently occurring cancer. Progression on to an advanced metastatic malignancy (metCRC) is often indicative of poor prognosis, as the 5-year survival rates of patients decline rapidly. Despite the availability of many systemic therapies for the management of metCRC, the long-term efficacies of these regimens are often hindered by the emergence of treatment resistance due to intratumoral and intertumoral heterogeneity. Furthermore, not all systemic therapies have associated biomarkers that can accurately predict patient responses. Hence, a functional personalised oncology (FPO) approach can enable the identification of patient-specific combinatorial vulnerabilities and synergistic combinations as effective treatment strategies. To this end, we established a panel of CRC patient-derived organoids (PDOs) as clinically relevant biological systems, of which three pairs of matched metCRC PDOs were derived from the primary sites (ptCRC) and metastatic lesions (mCRC). Histological and genomic characterisation of these PDOs demonstrated the preservation of histopathological and genetic features found in the parental tumours. Subsequent application of the phenotypic-analytical drug combination interrogation platform, Quadratic Phenotypic Optimisation Platform, in these pairs of PDOs identified patient-specific drug sensitivity profiles to epigenetic-based combination therapies. Most notably, matched PDOs from one patient exhibited differential sensitivity patterns to the rationally designed drug combinations despite being genetically similar. These findings collectively highlight the limitations of current genomic-driven precision medicine in guiding treatment strategies for metCRC patients. Instead, it suggests that epigenomic profiling and application of FPO could complement the identification of novel combinatorial vulnerabilities to target synchronous ptCRC and mCRC., (© 2024. The Author(s).)

Viruses are a key component of the colon microbiome, but the relationship between virome and colorectal cancer (CRC) remains poorly understood. We seek to identify alterations in the viral community that is characteristic of CRC and examine if they persist after surgery. Forty-nine fecal samples from 25 non-cancer (NC) individuals and 12 CRC patients, before and 6-months after surgery, were collected for metagenomic analysis. The fecal virome of CRC patients demonstrated an increased network connectivity as compared to NC individuals. Co-exclusion of influential viruses to bacterial species associated with healthy gut status was observed in CRC, suggesting an altered virome induced a change in the healthy gut bacteriome. Network analysis revealed lower connectivity within the virome and trans-kingdom interactions in NC. After surgery, the number of strong correlations decreased for trans-kingdom and within the bacteria and virome networks, indicating lower connectivity within the microbiome. Some co-occurrence patterns between dominant viruses and bacteria were also lost after surgery, suggesting a possible return to the healthy state of gut microbiome. Microbial signatures characteristic of CRC include an altered virome besides an altered bacterial composition. Elevated viral correlations and network connectivity were observed in CRC patients relative to healthy individuals, alongside distinct changes in the cross-kingdom correlation network unique to CRC patients. Some patterns of dysbiosis persist after surgery. Future studies should seek to verify if dysbiosis truly persists after surgery in a larger sample size with microbiome data collected at various time points after surgery to explore if there is field-change in the remaining colon, as well as to examine if persistent dysbiosis correlates with patient outcomes., (© 2024. The Author(s).)

Background: Surgical high dependency (SHD) allows for intermediate care provision between general ward (GW) and intensive care unit (ICU) for surgical patients but no universally accepted admission criteria exists. Unnecessary SHD admissions should be minimized to limit resource wastage and maintain spare critical care capacity. This study evaluates the utility of SHD admissions following elective laparoscopic colectomy by comparing post-operative outcomes and interventions performed between SHD and GW patients., Methodology: A retrospective review of all colorectal cancer patients who underwent elective laparoscopic colectomy in our institution between January 2019 and December 2021 was conducted. Patients converted to open surgery or admitted to IC post-operatively were excluded. Peri-operative parameters and outcomes between patients admitted to GW and SHD post-operatively were evaluated., Results: The cohort comprised 393 patients. There were 153 patients (38.93%) who required SHD admission. SHD patients had higher American Society of Anesthesiology (ASA) scores, body mass index, age and intra-operative blood loss. Majority of post-operative morbidity were minor (Clavien-Dindo II or lower) in both groups and the interventions required were safely instituted in both SHD and GW. None of the patients in the cohort required inotropic or ventilatory support in the SHD., Conclusions: GW patients were "healthier" but post-operative morbidity and interventions required were similar to the SHD group. Nonetheless, treatment delays, absence of continuous monitoring, and decreased nurse-to-patient ratio may be significant for patients with limited physiological reserves. Further studies should evaluate safety and cost-effectiveness of managing high risk surgical patients in GW using continuous remote vital signs monitoring., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

With the increase in carbapenem-resistant A. baumannii (CRAB) infections, there has been a resurgence in the use of polymyxins, specifically colistin (COL). Since the reintroduction of COL-based regimens in treating CRAB infections, several COL-resistant A. baumannii isolates have been identified, with the mechanism of resistance heavily linked with the loss of the lipopolysaccharide (LPS) layer of the bacterial outer membrane through mutations in lpxACD genes or the pmrCAB operon. SPR206, a novel polymyxin derivative, has exhibited robust activity against multidrug-resistant (MDR) A. baumannii . However, there is a dearth of knowledge regarding its efficacy in comparison with other A. baumannii -active therapeutics and whether traditional polymyxin (COL) mediators of A. baumannii resistance also translate to reduced SPR206 activity. Here, we conducted susceptibility testing using broth microdilution on 30 A. baumannii isolates (17 COL-resistant and 27 CRAB), selected 14 COL-resistant isolates for genomic sequencing analysis, and performed time-kill analyses on four COL-resistant isolates. In susceptibility testing, SPR206 demonstrated a lower range of minimum inhibitory concentrations (MICs) compared with COL, with a four-fold difference observed in MIC 50 values. Mutations in lpxACD and/or pmrA and pmrB genes were detected in each of the 14 COL-resistant isolates; however, SPR206 maintained MICs ≤ 2 mg/L for 9/14 (64%) of the isolates. Finally, SPR206-based combination regimens exhibited increased synergistic and bactericidal activity compared with COL-based combination regimens irrespective of the multiple resistance genes detected. The results of this study highlight the potential utility of SPR206 in the treatment of COL-resistant A. baumannii infections.

Background: We aimed to compare the clinical features and severity of the Omicron and Delta variant infections among children hospitalized for coronavirus disease 2019 (COVID-19)., Methods: Children 12 years old or less hospitalized for COVID-19 across five hospitals between January 1, 2021 and March 31, 2022 were identified using the state's pediatric COVID-19 registry. Delta and Omicron-infected patients without previous COVID-19 infection, COVID-19 vaccination, or co-infections were propensity-score matched 1:1 to control for differences in baseline characteristics. Clinical manifestations, treatments, and outcomes were analyzed. Disease severity was assessed using an adapted WHO ordinal scale., Results: Of the initial 1367 patients, 668 had Delta infection and 699 had Omicron infection. Propensity-score matching produced 558 matched pairs. Patients with Omicron infection were more likely to present with croup (the odds ratio, OR, was 10.87, with a 95% confidence interval, CI, ranging from 2.54 to 46.59), lower respiratory tract infection (OR 2.32, 95% CI, 1.48-3.64) and seizures (OR 8.39, 95% CI, 5.04-13.99) compared with those with Delta infection. Omicron was associated with increased odds of moderate/severe disease (OR 6.14, 95% CI, 4.72-7.99) and a greater need for intravenous fluid therapy (OR 6.00, 95% CI, 4.29-8.39), corticosteroids (OR 3.08, 95% CI, 1.66-5.72), empirical antibiotics (OR 1.70, 95% CI, 1.10-2.64), and low-flow nasal oxygen therapy (OR 3.68, 95% CI, 2.17-6.22) in comparison with Delta., Conclusion: Children hospitalized with Omicron infection demonstrated a distinct clinical profile compared to those with Delta infection, with increased likelihood of moderate/severe disease and higher utilization of health-care resources., (© 2024 Japan Pediatric Society.)

An increasing number of reports have described the pathogenic nature of several non-classical Bordetella spp. Among them, Bordetella hinzii and Bordetella pseudohinzii have been implicated in a myriad of respiratory-associated infections in humans and animals. We report the isolation of a genetically close relative of B. hinzii and B. pseudohinzii from the sputum of a woman in her early 60s with extensive bronchiectasis who presented with fever and brown colored sputum. The isolate had initially been identified as Bordetella avium by API 20NE, the identification system for non-enteric Gram-negative rod bacteria. Sequencing of the 16S rDNA, ompA , nrdA , and genes used in the Bordetella multilocus sequence typing scheme could not resolve the identity of this Bordetella isolate. Whole-genome single nucleotide polymorphism analysis positioned the isolate between B. hinzii and B. pseudohinzii in the phylogenetic tree, forming a distinct cluster. Whole-genome sequencing enabled the further identification of this rare organism, and should be considered for wider applications, especially the confirmation of organism identity in the clinical diagnostic microbiology laboratory., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Background: Health-related quality of life (HRQOL) is an increasingly important outcome in colorectal cancer (CRC) treatment. Established thresholds for clinical importance (TCI) permit an absolute interpretation of HRQOL scores but less emphasis has been placed on whether these can be used in a predictive manner. This study aimed to examine if patients' baseline HRQOL functioning scores, subgrouped based on TCI, would significantly predict HRQOL over time., Methods: 211 CRC patients were prospectively followed up from diagnosis to 18 months after surgery. Patients were administered the EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30) at each timepoint. Baseline demographic and clinical data were extracted from electronic medical records., Results: Only the physical and emotional functioning scales of the EORTC QLQ-C30 were utilised with their respective TCIs (score of ≤83 for physical; ≤71 for emotional). Physical functioning was below-threshold for most patients at pre-discharge (81.77 %) and 1-month (56.48 %) before stabilising to baseline proportions by 6-month. For emotional functioning, 22.04 %-30.98 % of patients were below-threshold between baseline to 3-month, stabilising to approximately 14.00 % after 6-month. Baseline TCI subgrouping was significantly associated with change in HRQOL scores over time for both the physical (β = 14.09, 95 % CI: 8.22, 19.97) and emotional (β = 25.66, 95 % CI: 18.79, 32.53) functioning scales (p < 0.01)., Conclusion: EORTC QLQ-C30 TCIs can be utilised not just to concretely identify clinically significant impairments in presenting CRC patients, but also as potential predictive tools towards more value-driven delivery of pre- and post-surgical supportive and allied healthcare., 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., (© 2023 Published by Elsevier Ltd.)

Background: Identifying host factors is key to understanding RNA virus pathogenicity. Besides proteins, RNAs can interact with virus genomes to impact replication., Results: Here, we use proximity ligation sequencing to identify virus-host RNA interactions for four strains of Zika virus (ZIKV) and one strain of dengue virus (DENV-1) in human cells. We find hundreds of coding and non-coding RNAs that bind to DENV and ZIKV viruses. Host RNAs tend to bind to single-stranded regions along the virus genomes according to hybridization energetics. Compared to SARS-CoV-2 interactors, ZIKV-interacting host RNAs tend to be downregulated upon virus infection. Knockdown of several short non-coding RNAs, including miR19a-3p, and 7SK RNA results in a decrease in viral replication, suggesting that they act as virus-permissive factors. In addition, the 3'UTR of DYNLT1 mRNA acts as a virus-restrictive factor by binding to the conserved dumbbell region on DENV and ZIKV 3'UTR to decrease virus replication. We also identify a conserved set of host RNAs that interacts with DENV, ZIKV, and SARS-CoV-2, suggesting that these RNAs are broadly important for RNA virus infection., Conclusions: This study demonstrates that host RNAs can impact virus replication in permissive and restrictive ways, expanding our understanding of host factors and RNA-based gene regulation during viral pathogenesis., (© 2023. The Author(s).)

Competing Interests: The authors declare that they have no conflict of interest.

Racially and ethnically minoritized (REM) patients are disproportionately impacted by infectious diseases. In our study, REM patients were more likely to receive care for urinary tract infections in the emergency department or urgent care, were younger, and were more likely to have higher social vulnerability., Competing Interests: Jacinda C. Abdul-Mutakabbir has served on advisory boards and received an honorarium for Shionogi, Entasis Therapeutics, CSL Sequiris, Innoviva Specialty Therapeutics, and Abbvie. All other authors have no conflicts of interest to declare., (© The Author(s) 2023.)

Self-isolation was common in the first year of COVID-19. While necessary, it also increased vulnerability to adverse mental health among elderly (i.e. aged 60 and above). This review seeks to summarise the outcomes, measures, and protective and risk factors of elderly mental health in the first year of COVID-19. Four international databases were systematically searched from inception to August 2021. Forty-five studies examining elderly mental health outcomes specific to COVID-19 were included - one was qualitative, 29 used cross-sectional quantitative methods, and 15 were longitudinal. Anxiety and depression were examined most commonly and consistently, largely with well-validated scales. Older age, female sex, poor financial status, being unmarried, high loneliness, low social engagement, low resilience and more severe pandemic measures were associated with poor elderly mental health outcomes. Ten of 13 longitudinal studies found deteriorations in elderly mental health outcomes over time. More consistent measures are needed to understand the pandemic's impact on elderly mental health. Our findings also suggest that socialising through digital mediums may not be helpful, and might even exacerbate loneliness. While the elderly are generally considered a high-risk population, higher-risk subpopulations were identified. We conclude by suggesting a multilevel approach to safeguard elderly mental health for future crises., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Racially and ethnically minoritized (REM) patients are disproportionately affected by infectious diseases, including candidemia. REM patients with candidemia were significantly younger, with trends toward more risk factors for candidemia and longer lengths of stay. Although Candida parapsilosis was more common in REM patients, there were no differences in mortality rates.

Importance: Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning., Objective: To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates., Evidence Review: The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019., Findings: In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia., Conclusions and Relevance: In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.

Background: Bruton's tyrosine kinase (BTK) is a cytoplasmic protein involved in the B cell development. X-linked agammaglobulinemia (XLA) is caused by mutation in the BTK gene, which results in very low or absent B cells. Affected males have markedly reduced immunoglobulin levels, which render them susceptible to recurrent and severe bacterial infections. Methods: Patients suspected with X-linked agammaglobulinemia were enrolled during the period of 2010-2018. Clinical summary, and immunological profiles of these patients were recorded. Peripheral blood samples were collected for monocyte BTK protein expression detection and BTK genetic analysis. The medical records between January 2020 and June 2023 were reviewed to investigate COVID-19 in XLA., Results: Twenty-two patients (from 16 unrelated families) were molecularly diagnosed as XLA. Genetic testing revealed fifteen distinct mutations, including four splicing mutations, four missense mutations, three nonsense mutations, three short deletions, and one large indel mutation. These mutations scattered throughout the BTK gene and mostly affected the kinase domain. All mutations including five novel mutations were predicted to be pathogenic or deleterious by in silico prediction tools. Genetic testing confirmed that eleven mothers and seven sisters were carriers for the disease, while three mutations were de novo . Flow cytometric analysis showed that thirteen patients had minimal BTK expression (0-15%) while eight patients had reduced BTK expression (16-64%). One patient was not tested for monocyte BTK expression due to insufficient sample. Pneumonia (n=13) was the most common manifestation, while Pseudomonas aeruginosa was the most frequently isolated pathogen from the patients (n=4). Mild or asymptomatic COVID-19 was reported in four patients., Conclusion: This report provides the first overview of demographic, clinical, immunological and genetic data of XLA in Malaysia. The combination of flow cytometric assessment and BTK genetic analysis provides a definitive diagnosis for XLA patients, especially with atypical clinical presentation. In addition, it may also allow carrier detection and assist in genetic counselling and prenatal diagnosis., 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 © 2023 Chear, Ismail, Chan, Noh, Kassim, Latiff, Gill, Ramly, Tan, Sundaraj, Choo, Mohamed, Baharin, Zamri, Yahya, Mohamad and Ripen.)

Background: Outpatient parenteral antimicrobial therapy (OPAT) and complex outpatient antimicrobial therapy (COpAT) are common practice in the management of infectious diseases (IDs). However, providing OPAT/COpAT can pose significant challenges pre- and post-discharge, particularly in vulnerable patient populations., Objectives: The objective of this study is to assess outpatient complications related to OPAT/COpAT in patients discharged with a home health services referral and to identify pre- and post-discharge intervention opportunities and the associated cost-savings that could be achieved with a multidisciplinary ID team-run OPAT/COpAT program., Design/methods: This is a retrospective cohort study of patients who were discharged with OPAT/COpAT through home health services over a 3-month study period. Data on potential pre-discharge interventions and post-discharge complications were recorded., Results: Medication-related issues were the most common pre-discharge complications, accounting for more than 50% of identified intervention opportunities. More than half of the included patients experienced at least one documented outpatient complication post-discharge with peripherally inserted central catheter-line-related complication (20.7%) being the most common issue. Using previously published cost-estimates, the implementation of a designated pre- and post-discharge OPAT/COpAT program could have saved over $100,000 over the 3-month study period., Conclusion: A multidisciplinary OPAT/COpAT program located in a high social vulnerable area can help reduce complications related to a patient's antimicrobial therapy. Medication-related issues represent a major area for potential intervention. Our findings suggest that a multidisciplinary ID team will have ample opportunities to improve the transition of care, at both pre- and post-discharge, for patients requiring antimicrobial therapy., Competing Interests: JAM has served on an advisory committee/board for Shionogi Inc., and Entasis Therapeutics and received an honorarium. All of the authors have no conflicts to report., (© The Author(s), 2023.)

Introduction: This study determines the sensitivity and specificity of positron emission tomography/magnetic resonance imaging (PET/MRI) parameters in predicting treatment response in patients with localised rectal cancer who have undergone preoperative chemoradiotherapy (CRT)., Method: Patients with stage I-III adenocarcinoma of the rectum planned for preoperative CRT followed by surgery were recruited. Patients had PET/MRI scans at baseline and 6-8 weeks post-CRT. Functional MRI and PET parameters were assessed for their diagnostic accuracy for tumour regression grade (TRG). Nonparametric receiver operating characteristic analysis was employed to determine the area under the ROC curve (AUC), and the sensitivity and specificity of each quantile cut-off., Results: A total of 31 patients were recruited, of whom 20 completed study protocol. All patients included had mid or lower rectal tumours. There were 16 patients (80%) with node-positive disease at presentation. The median time to surgery was 75.5 days (range 52-106 days). Histopathological assessment revealed 20% good responders (TRG 1/2), and the remaining 80% of patients had a poor response (TRG 3/4). When predicting good responders, the AUC values for percent maximum thickness reduction and percent apparent diffusion coefficient (ADC) change were 0.82 and 0.73, respectively. A maximum thickness reduction cut-off of >47% and a percent ADC change of >20% yielded a sensitivity and specificity of 75%/95% and 75%/73%, respectively., Conclusion: Parameters such as percent maximum thickness reduction and percent ADC change may be useful for predicting good responders in patients undergoing preoperative CRT for rectal cancer. Larger studies are warranted to establish the utility of PET/MRI in rectal cancer staging.

Background and Objectives : It remains unclear which domains of preoperative health-related quality of life (HRQOL) and mental health are predictive of postoperative clinical and patient-reported outcomes in colorectal cancer (CRC) patients. Materials and Methods: A prospective cohort of 78 CRC patients undergoing elective curative surgery was recruited. The EORTC QLQ-C30 and HADS questionnaires were administered preoperatively and one month after surgery. Results: Preoperative cognitive functioning scores (95% CI 0.131-1.158, p = 0.015) and low anterior resection (95% CI 14.861-63.260, p = 0.002) independently predicted poorer 1-month postoperative global QOL. When postoperative complications were represented using the comprehensive complication index (CCI), poorer preoperative physical function scores were associated with higher CCI scores (B = -0.277, p = 0.014). Preoperative social function score (OR = 0.925, 95% CI 0.87 to 0.99; p = 0.019) was an independent predictor for 30-day readmission, while physical functioning score (OR = -0.620, 95% CI -1.073--0.167, p = 0.008) was inversely related to the length of hospitalization. The overall regressions for 1-month postoperative global QOL (R 2 : 0.546, F: 1.961, p = 0.023) and 30-day readmission (R 2 : 0.322, χ2: 13.129, p < 0.001) were statistically significant. Conclusions: Various QLQ-C30 domains were found to be predictive of postoperative outcomes, including complications, readmission, and length of hospitalization. Preoperative cognitive dysfunction and low AR were independent predictors of poorer postoperative global QOL. Future research should seek to examine the efficacy of targeting specific baseline QOL domains in improving clinical as well as patient-reported outcomes after CRC surgery.

Background: Children account for a significant proportion of COVID-19 hospitalizations, but data on the predictors of disease severity in children are limited. We aimed to identify risk factors associated with moderate/severe COVID-19 and develop a nomogram for predicting children with moderate/severe COVID-19., Methods: We identified children ≤ 12 years old hospitalized for COVID-19 across five hospitals in Negeri Sembilan, Malaysia, from 1 January 2021 to 31 December 2021 from the state's pediatric COVID-19 case registration system. The primary outcome was the development of moderate/severe COVID-19 during hospitalization. Multivariate logistic regression was performed to identify independent risk factors for moderate/severe COVID-19. A nomogram was constructed to predict moderate/severe disease. The model performance was evaluated using the area under the curve (AUC), sensitivity, specificity, and accuracy., Results: A total of 1,717 patients were included. After excluding the asymptomatic cases, 1,234 patients (1,023 mild cases and 211 moderate/severe cases) were used to develop the prediction model. Nine independent risk factors were identified, including the presence of at least one comorbidity, shortness of breath, vomiting, diarrhea, rash, seizures, temperature on arrival, chest recessions, and abnormal breath sounds. The nomogram's sensitivity, specificity, accuracy, and AUC for predicting moderate/severe COVID-19 were 58·1%, 80·5%, 76·8%, and 0·86 (95% CI, 0·79 - 0·92) respectively., Conclusion: Our nomogram, which incorporated readily available clinical parameters, would be useful to facilitate individualized clinical decisions., (© 2023. The Author(s).)

Endothelial cells line the inner surface of all blood and lymphatic vessels, creating a semi-permeable barrier regulating fluid and solute exchange between blood or lymph and their surrounding tissues. The ability of a virus to cross the endothelial barrier is an important mechanism that facilitates virus dissemination in the human body. Many viruses are reported to alter endothelial permeability and/or cause endothelial cell barrier disruption during infection, which is able to cause vascular leakage. The current study describes a real-time cell analysis (RTCA) protocol, using a commercial real-time cell analyzer to monitor endothelial integrity and permeability changes during Zika virus (ZIKV) infection of the human umbilical vein endothelial cells (HUVECs). The impedance signals recorded before and after ZIKV infection were translated to cell index (CI) values and analyzed. The RTCA protocol allows the detection of transient effects in the form of cell morphological changes during a viral infection. This assay could also be useful for studying changes in the vascular integrity of HUVECs in other experimental setups.

Racial differences in Clostridioides difficile infection (CDI) outcomes have been reported. In this study, minoritized patients with CDIs had prolonged hospitalizations and increased intensive care unit admissions. Chronic kidney disease was shown to partially mediate the relationship between race or ethnicity and severe CDI. Our findings suggest potential areas for equitable interventions.

Background: Compensatory movements are commonly observed in older adults with stroke during upper extremity (UE) motor rehabilitation, which could limit their motor recovery., Aim: This study aims to develop a compensation-aware virtual rehabilitation system (VRS) that can detect compensatory movements and improve the outcome of UE rehabilitation in community-dwelling older adults with stroke., Methods: The VRS development includes three main components: (1) the use of thresholds for determining compensatory movements, (2) the algorithm for processing the kinematic data stream from Kinect to detect compensation in real-time, and (3) the audio-visual feedback to assist older adults with stroke to be aware of the compensation. Two studies were conducted following the VRS development, where Study 1 identified the value of thresholds for determining compensatory movements in two planar motor exercises, and Study 2 provided preliminary validation for the developed VRS by comparing two groups undergoing VR training or conventional training (CT) in a community rehabilitation center., Results: The VRS could effectively detect all determined compensatory movements and timely trigger feedback in response to the detected compensatory movements. The VR participants showed significant improvements in Fugl-Meyer Assessment-Upper Extremity (FMA-UE, p = 0.045) and Wolf Motor Function Test (WMFT, p = 0.009). However, the VR and CT groups had no significant differences in outcome measures., Conclusion: The VRS demonstrates the ability to detect compensation and the potential of assisting older adults with stroke to improve motor functions. Suggestions are given for further improvements of the VRS to support the older adult with stroke to reduce compensation., (© 2023. The Author(s).)

Zika virus (ZIKV) is a mosquito-borne virus belonging to the genus Flavivirus. ZIKV infection has been associated with congenital brain abnormalities and potentially Guillain-Barré syndrome in adults. Research on ZIKV to understand the disease mechanisms is important to facilitate vaccine and treatment development. The method of quantifying viruses is crucial and fundamental in the field of virology. The focus forming assay (FFA) is a virus quantification assay that detects the viral antigen with antibodies and identifies the infection foci of cells using the peroxidase immunostaining technique. The current study describes the virus propagation and quantification protocol using both 24-well and 96-well (high throughput) formats. Compared with other similar studies, this protocol has further described foci size optimization, which can serve as a guide to expand the use of this assay for other viruses. Firstly, ZIKV propagation is performed in Vero cells for 3 days. The culture supernatant containing ZIKV is harvested and quantitated using the FFA. Briefly, the virus culture is inoculated onto Vero cells and incubated for 2-3 days. Foci formation is then determined after optimized staining processes, including cell fixation, permeabilization, blocking, antibody binding, and incubation with peroxidase substrate. The stained virus foci are visualized using a stereo microscope (manual counting in 24-well format) or software analyzer (automated counting in 96-well format). The FFA provides reproducible, relatively fast results (3-4 days) and is suitable to be used for different viruses, including non-plaque-forming viruses. Subsequently, this protocol is useful for the study of ZIKV infection and could be used to detect other clinically important viruses.

Mis-sense mutations affecting TP53 promote carcinogenesis both by inactivating tumor suppression, and by conferring pro-carcinogenic activities. We report here that p53 DNA-binding domain (DBD) and transactivation domain (TAD) mis-sense mutants unexpectedly activate pro-carcinogenic epidermal growth factor receptor (EGFR) signaling via distinct, previously unrecognized molecular mechanisms. DBD- and TAD-specific TP53 mutants exhibited different cellular localization and induced distinct gene expression profiles. In multiple tissues, EGFR is stabilized by TAD and DBD mutants in the cytosolic and nuclear compartments respectively. TAD mutants promote EGFR-mediated signaling by enhancing EGFR interaction with AKT via DDX31 in the cytosol. Conversely, DBD mutants maintain EGFR activity in the nucleus, by blocking EGFR interaction with the phosphatase SHP1, triggering c-Myc and Cyclin D1 upregulation. Our findings suggest that p53 mutants carrying gain-of-function, mis-sense mutations affecting two different domains form new protein complexes that promote carcinogenesis by enhancing EGFR signaling via distinctive mechanisms, exposing clinically relevant therapeutic vulnerabilities., (© 2023. The Author(s).)

Objective: The uptake of breast and cervical cancer screening services among women in Singapore remains inadequate. Little is known about how gender norms influence women's decision to undergo these screening services in a multi-ethnic Asian context. This research aimed to explore how gender-based qualitative factors influence women's decision to screen., Methods: Qualitative data were collected using semi-structured interviews from 40 racially diverse women aged 25 and above who had visited polyclinics for their chronic disease management. Women were recruited using a purposive maximum variation sampling strategy to ensure representation of their views from the three major ethnic groups and based on inclusion criteria. Interviews were conducted either face-to-face or via telephone call. Interviews were audiotaped and lasted 30 minutes on average. Interviews were conducted until data saturation was reached. The data was transcribed and analysed thematically., Results: Gender norms and gender non-concordance with the healthcare professionals did not inhibit women from undergoing breast and cervical cancer screening services to a large extent. Women were empowered and had a central role in decision-making for screening services. Healthcare initiatives such as subsidies and mobile health applications facilitated the uptake of breast and cervical cancer screening services but can be improved further. Some of the barriers reported by Malay Muslims were not dissimilar to previous qualitative studies with women in this ethnic and religious group., Conclusion: Gender socialisation, empowerment, and healthcare initiatives did not inhibit our study participants' decision to undergo breast and cervical cancer screening services. However, new initiatives and strengthening of the existing healthcare initiatives are needed to overcome any remnants of gender-related nuances and convert non-doers into doers.

The reemergence of the Zika virus (ZIKV) infection in recent years has posed a serious threat to global health. Despite being asymptomatic or mildly symptomatic in a majority of infected individuals, ZIKV infection can result in severe manifestations including neurological complications in adults and congenital abnormalities in newborns. In a human host, ZIKV is primarily recognized by RIG-like receptors and Toll-like receptors that elicit anti-viral immunity through the secretion of type I interferon (IFN) to limit viral survival, replication, and pathogenesis. Intriguingly, ZIKV evades its host immune system through various immune evasion strategies, including suppressing the innate immune receptors and signaling pathways, mutation of viral structural and non-structural proteins, RNA modulation, or alteration of cellular pathways. Here, we present an overview of ZIKV recognition by the host immune system and the evasion strategies employed by ZIKV. Characterization of the host-viral interaction and viral disease mechanism provide a platform for the rational design of novel prophylactic and therapeutic strategies against ZIKV infection.

Background: Colorectal cancer (CRC) screening using the faecal immunochemical test (FIT) kits based on the detection of occult blood in stool is widely advocated in numerous screening programs worldwide. However, CRC is not commonly diagnosed in positive cases. We undertook this review to determine if there is evidence to suggest the use of opportunistic oesophago-gastro-duodenoscopy (OGD) in patients without CRC., Methods: A systematic review encompassing three electronic databases was performed. All peer-reviewed studies of FIT-positive patients who underwent either OGD and colonoscopy concurrently or OGD post-colonoscopy were included. Only studies from 2008 to 2022 using FIT kits were included to ensure studies not previously included in an earlier review were being analysed. A forward citation search of the included articles was also conducted to ensure no relevant articles were missed., Results: A total of 2409 records were extracted. Only four studies fulfilled the selection criteria and were included. Although the rates of abnormal OGD results were relatively high in the four studies, only 3 of 605 (0.50%) patients had gastric cancer in the entire review sample. No other malignancies were identified in all four studies. Other notable pathologies such as gastric polyps and gastritis were also reported., Conclusions: There is little overall evidence to recommend UGI screening for all FIT-positive patients following a colonoscopy. However, there may be a role for clinicians to consider opportunistic OGD in this group of patients. Future research should examine patient populations from other sociocultural contexts including cost-effective analysis when considering changes in health guidelines on UGI screening., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Choe 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: We describe the epidemiology, clinical characteristics, and outcomes of multisystem inflammatory syndrome in children (MIS-C) among children from Negeri Sembilan, Malaysia., Methods: A retrospective, multicentre, observational study was performed among children ≤15 years old who were hospitalized for MIS-C between January 18, 2021 and June 30, 2023. The incidence of MIS-C was estimated using reported SARS-CoV-2 cases and census population data. Descriptive analyses were used to summarize the clinical presentation and outcomes., Results: The study included 53 patients with a median age of 5.7 years (IQR 1.8-8.7 years); 75.5% were males. The overall incidence of MIS-C was approximately 5.9 cases per 1,000,000 person-months. Pediatric intensive care unit (PICU) admission was required for 22 (41.5%) patients. No mortalities were recorded. Children aged 6-12 years were more likely to present with cardiac dysfunction/shock (odds ratio [OR] 5.43, 95% confidence interval [CI] 1.67-17.66), whereas children below 6 years were more likely to present with a Kawasaki disease phenotype (OR 5.50, 95% CI 1.33-22.75). Twenty patients (37.7%) presented with involvement of at least four organ systems, but four patients (7.5%) demonstrated single-organ system involvement., Conclusion: An age-based variation in the clinical presentation of MIS-C was demonstrated. Our findings suggest MIS-C could manifest in a spectrum, including single-organ involvement. Despite the high requirement for PICU admission, the prognosis of MIS-C was favorable, with no recorded mortalities., (© 2023 Japan Pediatric Society.)

Background: This study aimed to describe the clinical characteristics and severity of young infants hospitalized with COVID-19 and study the relationship between breastfeeding and maternal COVID-19 vaccination on the severity of COVID-19., Methods: A retrospective, observational study was performed among infants aged 6 months and below hospitalized for COVID-19 in a tertiary state hospital in Malaysia between February 1 and April 30, 2022. The primary outcome was "serious disease," defined as pneumonia requiring respiratory support or dehydration with warning signs. Multivariate logistic regression was used to determine independent predictors for serious disease., Results: A total of 102 infants were included in the study; 53.9% were males with a median age of 11 weeks (interquartile range: 5-20 weeks). Sixteen patients (15.7%) had pre-existing comorbidities, including preterm birth. Fever was the most common presenting symptom (82.4%), followed by cough (53.9%), and rhinorrhea (31.4%). Forty-one infants (40.2%) presented with serious disease, warranting either respiratory support or intravenous fluid therapy for dehydration. Recent maternal COVID-19 vaccination was associated with a reduced risk of serious disease on univariate analysis but was not significant after multivariate adjustment (adjusted odds ratio [aOR] 0.39; 95% CI: 0.14-1.11; p = 0.08). Exclusive breastfeeding was protective against serious COVID-19 in young infants, independent of other confounding factors (aOR 0.21, 95% CI: 0.06-0.71; p = 0.01)., Conclusion: COVID-19 is a serious disease with non-specific clinical manifestations in young infants. Exclusive breastfeeding could play an important protective role., (© 2023 Japan Pediatric Society.)

Background: Colonoscopy is a commonly performed procedure, but most patients will not actually be found with colorectal cancer. Subsequent face-to-face consultations to explain post-colonoscopy findings are common despite the time and cost-saving benefits of teleconsultation, especially in a post-COVID-19 era. This exploratory retrospective study examined the proportion of post-colonoscopy follow-up consultations that could have been converted to teleconsultation within a tertiary hospital in Singapore., Methods: A retrospective cohort of all patients who underwent colonoscopy in the institution from July to September 2019 was identified. All follow-up face-to-face consultations related to the index colonoscopy from the scope date to 6 months post-colonoscopy were traced. Clinical data relevant to the index colonoscopy and these consultations were extracted from electronic medical records., Results: The cohort consisted of 859 patients (68.5% male, age range: 18-96 years). Of these, 15 (1.7%) had colorectal cancer, but the majority (n = 643, 74.9%) were scheduled for at least one post-colonoscopy visit - a total of 884 face-to-face clinical visits. The final sample was 682 (77.1%) face-to-face post-colonoscopy visits that did not involve any procedures performed or indicated the need for any subsequent follow-up., Conclusion: If such "unnecessary" post-colonoscopy consultations exist within our institution, then similar situations possibly occur elsewhere. As COVID-19 continues to periodically tax healthcare systems worldwide, preservation of resources will remain integral alongside quality standards of routine patient care. There is a need for detailed analyses and modeling to hypothesize potential savings by also considering the start-up and maintenance costs of switching to a teleconsultation-dominated system., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

A new fluorescent emitter based on π-extended benzothiadiazole was synthesized. The emitter exhibited a large molar extinction coefficient, a high quantum yield of 98% and a large radiative decay rate of 10 8 s -1 . Moreover, the obtained TADF-sensitized fluorescent OLED displayed excellent device performance with a high EQE max of 14.3%.

Zika virus (ZIKV) infection has emerged as a global health concern following epidemic outbreaks of severe neurological disorders reported in Pacific and Americas since 2016. Therefore, a rapid, sensitive and specific diagnostic test for ZIKV infection is critical for the appropriate patient management and the control of disease spread. A TaqMan minor groove binding (MGB) probe-based quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was developed based on the conserved sequence regions of 463 ZIKV NS2B genes. The designed ZIKV qRT-PCR assay was evaluated for its detection limit, strain coverage and cross-reactivity. We further assessed the clinical applicability of qRT-PCR assay for ZIKV RNA detection using a total 18 simulated clinical specimens. The detection limit of the qRT-PCR assay was 11.276 ZIKV RNA copies at the 95% probability level (probit analysis, p<= 0.05). Both Asian and African ZIKV strains were detected by the qRT-PCR assay without cross-reacting with DENV-1, DENV-2, DENV-3, DENV-4, CHIKV, JEV, LGTV, GETV and SINV. The qRT-PCR assay demonstrated a perfect agreement (k = 1.000, P < 0.001) with the reference assay; the sensitivity and specificity of the qRT-PCR assay were 100% (95% CI= 79.6-100) and 100% (95% CI= 43.9-100) respectively. The qRT-PCR assay developed in this study is a useful diagnostic tool for the broad coverage detection and quantification of both the Asian and African ZIKV strains.

Objectives: This study reported SARS-CoV-2 whole genome sequencing results from June 2021 to January 2022 from seven genome sequencing centers in Malaysia as part of the national surveillance program., Methods: COVID-19 samples that tested positive by reverse transcription polymerase chain reaction and with cycle threshold values <30 were obtained throughout Malaysia. Sequencing of SARS-CoV-2 complete genomes was performed using Illumina, Oxford Nanopore, or Ion Torrent platforms. A total of 6163 SARS-CoV-2 complete genome sequences were generated over the surveillance period. All sequences were submitted to the Global Initiative on Sharing All Influenza Data database., Results: From June 2021 to January 2022, Malaysia experienced the fourth wave of COVID-19 dominated by the Delta variant of concern, including the original B.1.617.2 lineage and descendant AY lineages. The B.1.617.2 lineage was identified as the early dominant circulating strain throughout the country but over time, was displaced by AY.59 and AY.79 lineages in Peninsular (west) Malaysia, and the AY.23 lineage in east Malaysia. In December 2021, pilgrims returning from Saudi Arabia facilitated the introduction and spread of the BA.1 lineage (Omicron variant of concern) in the country., Conclusion: The changing trends of circulating SARS-CoV-2 lineages were identified, with differences observed between west and east Malaysia. This initiative highlighted the importance of leveraging research expertise in the country to facilitate pandemic response and preparedness., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Benchmark comparisons in surgery allow identification of gaps in the quality of care provided. The aim of this study was to determine quality thresholds for high (HAR) and low (LAR) anterior resections in colorectal cancer surgery by applying the concept of benchmarking., Methods: This 5-year multinational retrospective study included patients who underwent anterior resection for cancer in 19 high-volume centres on five continents. Benchmarks were defined for 11 relevant postoperative variables at discharge, 3 months, and 6 months (for LAR). Benchmarks were calculated for two separate cohorts: patients without (ideal) and those with (non-ideal) outcome-relevant co-morbidities. Benchmark cut-offs were defined as the 75th percentile of each centre's median value., Results: A total of 3903 patients who underwent HAR and 3726 who had LAR for cancer were analysed. After 3 months' follow-up, the mortality benchmark in HAR for ideal and non-ideal patients was 0.0 versus 3.0 per cent, and in LAR it was 0.0 versus 2.2 per cent. Benchmark results for anastomotic leakage were 5.0 versus 6.9 per cent for HAR, and 13.6 versus 11.8 per cent for LAR. The overall morbidity benchmark in HAR was a Comprehensive Complication Index (CCI®) score of 8.6 versus 14.7, and that for LAR was CCI® score 11.9 versus 18.3., Conclusion: Regular comparison of individual-surgeon or -unit outcome data against benchmark thresholds may identify gaps in care quality that can improve patient outcome., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: All patients who underwent curative resection for colorectal cancer (CRC) are frequently reviewed in tertiary institutions to ensure timely detection of any disease recurrence. There has been no local study that evaluated the feasibility of monitoring their condition in the community as a possible new model of care. This study henceforth seeks to understand CRC patients' views and receptiveness of having their surveillance consultations conducted in a community setting., Methods: We convenience sampled Stage I and II CRC patients who were within five years post-operation in the outpatient clinics. An open-ended questionnaire aimed at elucidating their perception towards cancer surveillance in a community setting was administered. Content analysis was used to group and quantify responses from participants., Results: Twenty-five participants agreed to participate in the study. Only 48% of the participants felt that having phlebotomy procedures in a community or home setting was acceptable. Participants were less willing to be reviewed by a physician who is not their primary surgeon, with only 32% agreeable to seeing a different doctor for surveillance if given a choice. However, most participants were open to having a telephone consultation in place of a physical face-to-face consultation before (72%) and after (76%) going through medical imaging., Conclusions: Participants remained keen to be managed by their primary surgeons and were hesitant towards having their follow-up surveillance consultations in community and primary care settings. Further studies should be conducted to understand whether these perceptions are generalisable, and if more can be done to change public perception towards the role of community and primary care institutions., (© 2022. The Author(s).)

Despite the global prevalence of colorectal cancer (CRC) and efforts in screening advocacy, screening uptake remains relatively low. Considering the greater accessibility and popularity of telemedicine in behaviour change interventions, this meta-analysis seeks to examine the usefulness of digital interventions in promoting CRC screening uptake as compared to existing non-digital strategies. A systematic search on five databases identified articles published before September 2022. Randomized controlled trials comparing the effectiveness of digital interventions to usual care were included and assessed using the Cochrane's Risk of Bias tool. Effectiveness of interventions was measured by CRC screening completion rates, and pooled effect sizes were computed for both digital intervention subtypes identified - decision-making aids and tailored educational interventions. 14 studies (17,075 participants) assessed to have low or some risk of bias were included in this meta-analysis. A random-effects model revealed that digital interventions were more likely to promote CRC screening uptake (OR = 1.31, 95% CI: 1.11-1.56), and using a decision-making aid was almost 1.5 times more likely to result in screening completion (i.e., completed a colorectal investigation using stool-based or direct visualization test) (OR = 1.42, 95% CI: 1.24-1.63). Meanwhile, the tailored educational intervention subtype failed to achieve statistical significance in promoting screening uptake, bearing in mind the significant heterogeneity across studies (I 2  = 88.6%). Digital decision-making aids significantly improved CRC screening uptake compared to tailored digital educational interventions and usual care. However, as all included studies were conducted in Western settings, its role in augmenting existing CRC screening promotion strategies especially among Asians should be further evaluated., 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 © 2022. Published by Elsevier Inc.)

Background: A urinary tract infection (UTI) is one of the most common types of infections affecting the urinary tract. When bacteria enter the bladder or kidney and multiply in the urine, a URI can occur. The urethra is shorter in women than in men, which makes it easier for bacteria to reach the bladder or kidneys and cause infection. A comparison of the research differences between Urology and Nephrology (UN) authors regarding UTI pertaining to the 4 areas (i.e., Chronic Kidney Disease, Hemodialysis, Peritoneal Dialysis, and Renal Transplantation [CHPR]) is thus necessary. We propose and verify 2 hypotheses: CHPR-related articles on UTI have equal journal impact factors (JIFs) in research achievements (RAs) and UN authors have similar research features (RFs)., Methods: Based on keywords associated with UTI and CHPR in titles, subject areas, and abstracts since 2013, we obtained 1284 abstracts and their associated metadata (e.g., citations, authors, research institutes, departments, countries of origin) from the Web of Science core collection. There were 1030 corresponding and first (co-first) authors with hT-JIF-indices (i.e., JIF was computed using hT-index rather than citations as usual). The following 5 visualizations were used to present the author's RA: radar, Sankey, time-to-event, impact beam plot, and choropleth map. The forest plot was used to distinguish RFs by observing the proportional counts of keyword plus in Web of Science core collection between UN authors., Results: It was observed that CHPR-related articles had unequal JIFs (χ2 = 13.08, P = .004, df = 3, n = 1030) and UN departments had different RFs (Q = 53.24, df = 29, P = .004). In terms of countries, institutes, departments, and authors, the United States (hT-JIF = 38.30), Mayo Clinic (12.9), Nephrology (19.14), and Diana Karpman (10.34) from Sweden had the highest hT-JIF index., Conclusion: With the aid of visualizations, the hT-JIF-index and keyword plus were demonstrated to assess RAs and distinguish RFs between UN authors. A replication of this study under other topics and in other disciplines is recommended in the future, rather than limiting it to UN authors only, as we did in this study., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Evidence on the long-term effects of weight management smartphone apps on various weight-related outcomes remains scarce., Objective: In this review, we aimed to examine the effects of smartphone apps on anthropometric, metabolic, and dietary outcomes at various time points., Methods: Articles published from database inception to March 10, 2022 were searched, from 7 databases (Embase, CINAHL, PubMed, PsycINFO, Cochrane Library, Scopus, and Web of Science) using forward and backward citation tracking. All randomized controlled trials that reported weight change as an outcome in adults with overweight and obesity were included. We performed separate meta-analyses using random effects models for weight, waist circumference, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, blood glucose level, blood pressure, and total energy intake per day. Methodological quality was assessed using the Cochrane Risk of Bias tool., Results: Based on our meta-analyses, weight loss was sustained between 3 and 12 months, with a peak of 2.18 kg at 3 months that tapered down to 1.63 kg at 12 months. We did not find significant benefits of weight loss on the secondary outcomes examined, except for a slight improvement in systolic blood pressure at 3 months. Most of the included studies covered app-based interventions that comprised of components beyond food logging, such as real-time diet and exercise self-monitoring, personalized and remote progress tracking, timely feedback provision, smart devices that synchronized activity and weight data to smartphones, and libraries of diet and physical activity ideas., Conclusions: Smartphone weight loss apps are effective in initiating and sustaining weight loss between 3 and 12 months, but their effects are minimal in their current states. Future studies could consider the various aspects of the socioecological model. Conversational and dialectic components that simulate health coaches could be useful to enhance user engagement and outcome effectiveness., Trial Registration: International Prospective Register of Systematic Reviews (PROSPERO) CRD42022329197; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=329197., (©Han Shi Jocelyn Chew, Wee Ling Koh, Janelle Shaina Hui Yi Ng, Ker Kan Tan. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 21.09.2022.)

Purpose: Multimodal prehabilitation aims to prepare frail older patients for major surgery. The objective of this review is to determine the benefits of pre-operative multimodal prehabilitation compared to standard care in older patients., Methods: Data sources included MEDLINE, EMBASE, CENTRAL, CINAHL and PsychINFO. They were searched from inception to September 2021. Only randomized controlled trials (RCT) with an average study population age ≥ 65 that had undergone major abdominal operation with at least two components (physical, nutritional, psychological) of prehabilitation programs were included., Results: Nine RCTs were included with a total of 823 patients, of whom 705 completed the study with 358 undergoing prehabilitation and 347 were controls. Significantly lower complications were observed in the prehabilitation group compared to control (OR 0.67; 95% CI 0.46 to 0.99; p = 0.04; I 2  = 32%). A significant increase in 6-min walking distance (6MWD) from baseline to immediately prior to surgery (mean difference 35.1 m; 95%CI 11.6-58.4; p = 0.003; I 2  = 67%) and 8 weeks post-surgery (mean difference 44.9 m; 95%CI 6.0-83.8; p = 0.02; I 2  = 75%) was noted in the prehabilitation group. No difference was observed in length of stay (OR 0.59; 95% CI - 0.23 to 1.40; p = 0.16; I 2  = 91%) or 30-day emergency department visit (OR 0.72; 95% CI 0.41 to 1.26; p = 0.25; I 2  = 0%). Patient reported outcome measures were not significantly different., Conclusions: Amongst older patients, multimodal prehabilitation increases peri-operative functional capacity and may potentially decrease post-operative complications. Future studies should continue to focus on older patients who are frail as this is the group that prehabilitation would likely have a clinically significant impact on., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Enhanced recovery after surgery programs have improved patient outcomes following colorectal surgery. This has provided a platform for the consideration of ambulatory colectomies where patients are discharged within 24 hours after surgery. Although some studies have demonstrated its feasibility, the safety profile and patient eligibility criteria for discharge within 24 hours after surgery remain relatively ill-defined. This study provided a review of the patient selection criteria and postoperative outcomes shown in patients discharged within 24 hours after surgery., Methods: Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines were adhered to. A comprehensive search was performed on 3 electronic databases, and the relevant articles were identified. The primary outcome measures were postoperative morbidity and readmission rates. The different domains relevant to the selection of patients and perioperative care of patients discharged within 24 hours after surgery were also qualitatively assessed., Results: Eight studies were included, which involved a total of 1,229 patients. The majority of selected patients underwent elective laparoscopic colonic surgeries. The patient characteristics, such as age, comorbidities, obesity, and psychosocial environment, were important considerations. A close follow-up with home-based medical services was ideal in patients discharged within 24 hours after surgery. The readmission rates ranged from 0.0% to 9.0%. Despite morbidity rates of up to 26.7%, the majority of them were minor and classified as Clavien-Dindo Grade I to II., Conclusion: The use of programs related to discharge within 24 hours after surgery in colorectal surgery is safe, feasible, and practical in a select group of patients within a well-designed clinical framework and pathway. Future studies should compare patient outcomes following discharge within 24 hours after surgery with conventional enhanced recovery after surgery protocols. In addition, patient and caregiver perceptions, quality of life, and cost-effectiveness analysis should also be performed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

During the past decade, breakthroughs in sequencing technology have provided the basis for studies of the myriad ways in which microbial communities in and on the human body influence human health and disease. In almost every medical specialty, there is now a growing interest in accurate and quantitative profiling of the microbiota for use in diagnostic and therapeutic applications. However, the current next-generation sequencing approach for microbiome profiling is costly, requires laborious library preparation, and is challenging to scale up for routine diagnostics. Split, Amplify, and Melt analysis of BActeria-community (SAMBA), a novel multicolor digital melting polymerase chain reaction platform with unprecedented multiplexing capability is presented, and the capability to distinguish and quantify 16 bacteria species in mixtures is demonstrated. Subsequently, SAMBA is applied to measure the compositions of bacteria in the gut microbiome to identify microbial dysbiosis related to colorectal cancer. This rapid, low cost, and high-throughput approach will enable the implementation of microbiome diagnostics in clinical laboratories and routine medical practice., (© 2022 Wiley-VCH GmbH.)

Zika virus (ZIKV) has had a history in Malaysia since its first isolation in 1966. However, it is believed that the immunity status among forest fringe communities has been underreported. We conducted cross-sectional surveillance of forest fringe communities from 10 Orang Asli villages and their peripheral communities in Perak, Pahang, and Sabah in Malaysia. A total of 706 samples were collected from 2019 to 2020 and screened for ZIKV exposure using an anti-ZIKV IgG ELISA kit. A neutralization assay against ZIKV was used to confirm the reactive samples. The seroprevalence results reported from the study of this population in Malaysia were 21.0% (n = 148, 95% CI, 0.183-0.273) after confirmation with a foci reduction neutralization test. The presence of neutralizing antibodies provides evidence that the studied forest fringe communities in Malaysia have been exposed to ZIKV. Multivariate analysis showed that those older than 44 years and those with an education below the university level had been exposed significantly to ZIKV. In addition, higher seropositivity rates to ZIKV were also reported among secondary school students from Bentong (Pahang) and residents from Segaliud (Sabah). No associations were identified between Zika seropositivity and gender, household size, house radius to the jungle, and income level. The presence of neutralizing antibodies against ZIKV among the study population might indicate that the causative pathogen had already circulated widely in forest fringe regions. Intervention for vector control, protection from mosquito bites, and awareness improvement should be encouraged in this population.

There is growing interest in the role of gut microbiome in colorectal cancer (CRC), ranging from screening to disease recurrence. Our study aims to identify microbial markers characteristic of CRC and to examine if changes in bacteriome persist after surgery. Forty-nine fecal samples from 25 non-cancer (NC) individuals and 12 CRC patients, before and 6-months after surgery, were collected for analysis by bacterial 16S rRNA gene sequencing. Bacterial richness and diversity were reduced, while pro-carcinogenic bacteria such as Bacteroides fragilis and Odoribacter splanchnicus were increased in CRC patients compared to NC group. These differences were no longer observed after surgery. Comparison between pre-op and post-op CRC showed increased abundance of probiotic bacteria after surgery. Concomitantly, bacteria associated with CRC progression were observed to have increased after surgery, implying persistent dysbiosis. In addition, functional pathway predictions based on the bacterial 16S rRNA gene data showed that various pathways were differentially enriched in CRC compared to NC. Microbiome signatures characteristic of CRC comprise altered bacterial composition. Elements of these dysbiotic signatures persists even after surgery, suggesting possible field-change in remnant non-diseased colon. Future studies should involve a larger sample size with microbiome data collected at multiple time points after surgery to examine if these dysbiotic patterns truly persist and also correlate with disease outcomes., (© 2022. The Author(s).)