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Background: BK virus-associated nephropathy (BKVAN), caused by infection with or reactivation of BK virus, remains a challenge in kidney transplantation. Screening is recommended for all kidney transplant recipients. For those with clinically significant infection, reduction of immunosuppression is the cornerstone of management. There is no specific antiviral or immunomodulatory therapy sufficiently effective for routine use., Objectives: This review aimed to examine the benefits and harms of interventions for BK virus infection in kidney transplant recipients., Search Methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 5 September 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov., Selection Criteria: All randomised controlled trials (RCTs) and cohort studies investigating any intervention for the treatment or prevention of BKVAN for kidney transplant recipients., Data Collection and Analysis: Two authors independently assessed the study quality and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach., Main Results: Twelve RCTs (2669 randomised participants) were included. Six studies were undertaken in single centres, and six were multicentre studies; two of these were international studies. The ages of those participating ranged from 44 to 57 years. The length of follow-up ranged from three months to five years. All studies included people with a kidney transplant, and three studies included people with signs of BK viraemia. Studies were heterogeneous in terms of the type of interventions and outcomes assessed. The overall risk of bias was low or unclear. Intensive screening for the early detection of BK viraemia or BK viruria prevents graft loss (1 study, 908 participants: RR 0.00, 95% CI 0.00 to 0.05) and decreases the presence of decoy cells and viraemia at 12 months (1 study, 908 participants: RR 0.06, 95% CI 0.03 to 0.11) compared to routine care (high certainty evidence). No other outcomes were reported. Compared to placebo, fluoroquinolones may slightly reduce the risk of graft loss (3 studies, 393 participants: RR 0.37, CI 0.09 to 1.57; I 2 = 0%; low certainty evidence), probably makes little or no difference to donor-specific antibodies (DSA), may make little or no difference to BK viraemia and death, had uncertain effects on BKVAN and malignancy, but may increase the risk of tendonitis (2 studies, 193 participants: RR 5.66, CI 1.02 to 31.32; I 2 = 0%; low certainty evidence). Compared to tacrolimus (TAC), cyclosporin (CSA) probably makes little or no difference to graft loss and death, may make little or no difference to BKVAN and malignancy, but probably decreases BK viraemia (2 studies, 263 participants: RR 0.61, 95% CI 0.26 to 1.41; I 2 = 38%) and probably reduces the risk of new-onset diabetes after transplantation (1 study, 200 participants: RR 0.41, 95% CI 0.12 to 1.35) (both moderate certainty evidence). Compared to azathioprine, mycophenolate mofetil (MMF) probably makes little or no difference to graft loss and BK viraemia but probably reduces the risk of death (1 study, 133 participants: RR 0.43, 95% CI 0.16 to 1.16) and malignancy (1 study, 199 participants: RR 0.43, 95% CI 0.16 to 1.16) (both moderate certainty evidence). Compared to mycophenolate sodium (MPS), CSA has uncertain effects on graft loss and death, may make little or no difference to BK viraemia, but may reduce BKVAN (1 study, 224 participants: RR 0.06, 95% CI 0.00 to 1.20; low certainty evidence). Compared to immunosuppression dose reduction, MMF or TAC conversion to everolimus or sirolimus may make little or no difference to graft loss, BK viraemia or BKVAN (low certainty evidence). TAC conversion to sirolimus probably results in more people having a reduced BK viral load (< 600 copies/mL) than immunosuppression reduction (1 study, 30 participants: RR 1.31, 95% CI 0.90 to 1.89; moderate certainty evidence). Compared to MPS, everolimus had uncertain effects on graft loss and BK viraemia, may reduce BKVAN (1 study, 135 participants: 0.06, 95% CI 0.00 to 1.11) and may increase the risk of death (1 study, 135 participants: RR 3.71, 95% CI 0.20 to 67.35) (both low certainty evidence). Compared to CSA, everolimus may make little or no difference to BK viraemia, has uncertain effects on graft loss and BKVAN, but may increase the risk of death (1 study, 185 participants: RR 3.71, 95% CI 0.42 to 32.55; low certainty evidence). Compared to immunosuppression reduction, the leflunomide derivative FK778 may make little or no difference to graft loss, probably results in a greater reduction in plasma BK viral load (1 study, 44 participants: -0.60 copies/µL, 95% CI -1.22 to 0.02; moderate certainty evidence), but had uncertain effects on BKVAN and malignancy. Aggravated hypertension may be increased with KF778 (1 study, 46 participants: RR 8.23, 95% CI 0.50 to 135.40; low certainty evidence). There were no deaths in either group., Authors' Conclusions: Intense monitoring early after transplantation for BK viruria and BK viraemia is effective in improving BK virus infection outcomes as it helps with early detection of the infection and allows for a timely reduction in immunosuppression reduction. There is insufficient evidence to support any other intervention for BK virus infection in kidney transplant recipients., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: Parasite are living organisms which survive on another living being for their nourishment and survival. When these parasites resides on human body, they bring about inflammatory response. This inflammatory response leads to tissue reaction. Tissue response on microscopy appear as an eosinophilia, abscess and granulomas. This study was planned with the objective to know the frequency of parasite infection, tissue response in parasite infection and its comparison in terms of variables like age, sex and the type of parasite., Methods: This is a retrospective study, conducted in the department of pathology. A total of 26 cases of parasitic infections in human specimens reported in our department from January 2008 to December 2019 were included in this study. On all archived cases hematoxylin and eosin and where ever required periodic acid schiff was applied. These slides were thoroughly examined and clinicopathological correlation was studied., Results: Age range of patients was 5 years to 70 years. Maximum number of patients were belonging to 11-20 year age group. Male to female ratio was 1:2. Among the 26 cases, there were 9 cases (34.62%) of hydatid cyst, six cases of Entamoeba histolytica (23.07%), four cases of Enterobious vermicularis (15.38%), and two cases (7.69%) each of Ascaris lumbricoides , filaria and cysticercosis respectively. A specific tissue response seen in cysticercosis having chronic inflammatory cells, palisaded epithelioid cells granuloma and giant cell reaction while other showed inflammatory cells infiltration., Conclusion: Clinically diagnosis of parasitic infection in each and every case is not possible, similarly radiological investigation is also suggestive only. Histopathology examination is the benchmark investigation to diagnose parasite infection and tissue reaction to the host. Histopathology examination must be implicated in every case to identify parasite and tissue reaction so that the patients can be managed accordingly before the complications rises., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Chronic osteomyelitis resulting from foreign body entrapment in the pediatric mandible presents unique challenges in diagnosis and management. Habitual insertion of objects into the oral cavity by children can lead to serious complications such as discharging sinuses and osteomyelitis. We present a case of a 12-year-old boy with extra-oral pus discharge originating from the mandible, ultimately traced to an embedded iron nail adjacent to a carious first molar. Radiographic imaging played a crucial role in diagnosis, revealing the foreign object and. Long-term follow-up showed successful healing with prompt treatment. Prevention through parent education, meticulous examination, and interdisciplinary collaboration are emphasized to avoid such complications., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© Association of Otolaryngologists of India 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: Illicit drug use, particularly the synthetic opioid fentanyl, presents a significant global health challenge. Previous studies have shown that fentanyl enhances viral replication; yet, the mechanisms by which it affects HIV pathogenesis remain unclear. This study investigated the impact of fentanyl on HIV replication in CD4 + T lymphocytes., Methods: CD4 + T lymphocytes from HIV-negative donors were activated, infected with HIV NL4-3 , and treated with fentanyl. HIV proviral DNA and p24 antigen expression were quantified using real-time PCR and ELISA, respectively. Single-cell RNA libraries were analyzed to identify differentially expressed genes., Results: Results indicated that fentanyl treatment increased HIV p24 expression and proviral DNA levels, and naltrexone mitigated these effects. Single-cell RNAseq analysis identified significantly altered gene expression in CD4 + T lymphocytes., Discussion: The results of our findings suggest that fentanyl promotes HIV replication ex vivo , emphasizing the need for a deeper understanding of opioid-virus interactions to develop better treatment strategies for individuals with HIV and opioid use disorder., 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 Krishnan, Roskin, Meeds and Blackard.)

Vaccines are complex and a very diverse group of products with relatively long product lifecycles. The manufacturing programs for these vaccines need to be continually updated to comply with evolving regulatory expectations. Members of the Parenteral Drug Association (PDA) Vaccines Interest Group (VIG) authored and published PDA Technical Report No. 89 Strategies for Vaccine Development and Lifecycle Management (TR 89) which seeks to provide context to vaccine developers and manufacturers regarding key aspects of new or legacy vaccines such as control strategy from process development to vaccine lifecycle management, comparability and lifecycle management including technical, validation, quality and regulatory perspectives. To further explain and illustrate the concepts and topics discussed, seven relevant situations were selected as either case studies associated with changes implemented or proposed process development strategies, which are discussed in this article. The situations described are: working cell bank, modification or update of externally supplied product contact components for vaccine manufacturing, raw material change, new product at an existing site, vaccine development acceleration by leveraging existing platforms, selection and implementation of potency method, and modeling for stability forecast prediction. For each situation, the applicable key concepts from TR#89 are discussed as follows: Control Strategy, Prior Knowledge, Relying on PQS, Classification of Parameters, Validation Approach, Use of a Risk-based Approach, Comparability, Use of ICHQ12 and Additional Regulatory Considerations., (Copyright © 2024, Parenteral Drug Association.)

Here, we employ polymer physics models of chromatin to investigate the 3D folding of a 2 Mb wide genomic region encompassing the human LTN1 gene, a crucial DNA locus involved in key cellular functions. Through extensive Molecular Dynamics simulations, we reconstruct in silico the ensemble of single-molecule LTN1 3D structures, which we benchmark against recent in situ Hi-C 2.0 data. The model-derived single molecules are then used to predict structural folding features at the single-cell level, providing testable predictions for super-resolution microscopy experiments.

Cardiovascular diseases (CVDs) are the leading cause of premature morbidity and mortality globally. The identification of novel risk factors contributing to CVD onset and progression has enabled an improved understanding of CVD pathophysiology. In addition to the conventional risk factors like high blood pressure, diabetes, obesity and smoking, the role of gut microbiome and intestinal microbe-derived metabolites in maintaining cardiovascular health has gained recent attention in the field of CVD pathophysiology. The human gastrointestinal tract caters to a highly diverse spectrum of microbes recognized as the gut microbiota, which are central to several physiologically significant cascades such as metabolism, nutrient absorption, and energy balance. The manipulation of the gut microbial subtleties potentially contributes to CVD, inflammation, neurodegeneration, obesity, and diabetic onset. The existing paradigm of studies suggests that the disruption of the gut microbial dynamics contributes towards CVD incidence. However, the exact mechanistic understanding of such a correlation from a signaling perspective remains elusive. This review has focused upon an in-depth characterization of gut microbial metabolites and their role in varied pathophysiological conditions, and highlights the potential molecular and signaling mechanisms governing the gut microbial metabolites in CVDs. In addition, it summarizes the existing courses of therapy in modulating the gut microbiome and its metabolites, limitations and scientific gaps in our current understanding, as well as future directions of studies involving the modulation of the gut microbiome and its metabolites, which can be undertaken to develop CVD-associated treatment options. Clarity in the understanding of the molecular interaction(s) and associations governing the gut microbiome and CVD shall potentially enable the development of novel druggable targets to ameliorate CVD in the years to come.

Preservatives are critical ingredients in various pharmaceutical and consumer products. In particular, a high efficacy preservative system is essential in enhancing the shelf-life and safety of these products. However, the development of such a preservative system heavily relies on experimental approaches. In this study, molecular dynamics (MD) simulation was complemented with quantitative structure-activity relationship (QSAR) modelling to comprehensively evaluate polymer-preservative interactions between three different polymers (polyethylene terephthalate, PET; polypropylene, PP; and cellulose) and a series of preservatives from the classes of aliphatic, aromatic, and organic acids. First, adsorption of preservatives onto polymer surfaces was simulated in an aqueous environment. The preservatives did not adhere to hydrophilic cellulose, but most preservatives were adsorbed by PET and PP in distinct configurations. Interaction energies (IEs) between the preservatives and the polymers generally increase from cellulose to PP and PET. The diffusion coefficients of preservatives are dependent on polymer nature, preservative structure, and their resulting molecular interactions. Linear and low molecular weight preservatives exhibit higher diffusion coefficients in polymers. For a particular preservative, diffusion coefficients increased in the order of cellulose < PET < PP. Finally, using MD properties and molecular descriptors of preservatives, QSAR models were developed to identify key descriptors of preservatives and predict their IEs and diffusion coefficients in polymers. This study demonstrates a computational approach for identifying critical materials properties, and predicting polymer-preservative molecular interactions in water. Such an approach streamlines the rational selection and design of high efficacy preservative systems for various pharmaceutical, food and cosmetic products. Furthermore, the integrated computational strategy also reduces trial-and-error experimental efforts, thereby accelerating the development of high efficacy preservative systems.

Aims To assess if ambient temperature-related effects on serum potassium levels impact clinical decision-making. Methods This study is an ecological time series consisiting of 1 218 453 adult patients with at least one ACE inhibitor (ACEI) prescription who participate in a large UK primary care dataset.Descriptive statistics and a quasi-Poisson regression model using time series data at regular time intervals (monthly) were undertaken to examine the association between potassium measurements and ACEI/potassium supplement prescriptions. RESULTS: It is noted that correlating with lower ambient temperature, serum potassium values follow a seasonal pattern; peaks in winter months and troughs in summer. During summer months, there are clear annual spikes in the number of potassium prescriptions suggesting a change in prescribing practice during periods of potentially spurious hyperkalaemia. The converse pattern is seen in the ACEI prescription proportion which spikes annually during the winter period with lower average ambient temperatures. Our time series modelling demonstrated that each one unit increase in potassium is associated with a 33% increased rate of ACEI prescriptions (risk ratio, RR 1.33; 95% CI 1.12 to 1.59) and 63% decreased rate of potassium supplements (RR 0.37; 95% CI 0.32 to 0.43). CONCLUSIONS: Our findings highlight the seasonal pattern in serum potassium and we observe a corresponding alteration in prescribing practice for potassium sensitive medications. These findings demonstrate the importance of educating clinicians on the presence of seasonal potassium variability in addition to standard measurement error, and its potential impact on their prescribing activity., Competing Interests: Competing interests: JSC, KN and KMG are codirectors of DExtER operating division which is part of the University of Birmingham. DExtER operating division supports the extraction and preparing of healthcare data to support epidemiological analyses such as those seen in this article., (© 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 management of hepatic adenoma in transgender individuals undergoing gender-affirming hormone therapy remains unclear, especially whether treatment should be based on sex assigned at birth or therapy patient received. We presented a transgender man, female at birth, with hepatic adenomatosis with molecular profile differed from typical adenomas in cisgender males on testosterone. Discontinuing testosterone led to autoinfarction of the adenoma, allowing the avoidance of invasive treatments and resumption of gender-affirming hormone therapy. This case underscores the necessity for personalized care in the growing transgender population and challenges current consensus of treatment based on sex assigned at birth, emphasizing a tailored approach., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Over 95% of penicillin allergy labels are inaccurate and may be addressed in low-risk patients using direct oral penicillin challenge (DPC). This study explored the behaviour, attitudes and acceptability of patients, healthcare professionals (HCPs) and managers of using DPC in low-risk patients., Methods: Mixed-method, investigation involving patient interviews and staff focus groups at three NHS acute hospitals. Transcripts were coded using inductive and deductive thematic analysis informed by the Theoretical Domains Framework., Findings: Analysis of 43 patient interviews and three focus groups (28 HCPs: clinicians and managers) highlighted themes of 'knowledge', 'beliefs about capabilities and consequences', 'environmental context', 'resources', 'social influences', 'professional role and identity', 'behavioural regulation and reinforcement' and a cross-cutting theme of digital systems. Overall, study participants supported the DPC intervention. Patients expressed reassurance about being in a monitored, hospital setting. HCPs acknowledged the need for robust governance structures for ensuring clarity of roles and responsibilities and confidence., Conclusion: There were high levels of acceptability among patients and HCPs. HCPs recognised the importance of DPC. Complexities of penicillin allergy (de)labelling were highlighted, and issues of knowledge, risk, governance and workforce were identified as key determinants. These should be considered in future planning and adoption strategies for DPC., Competing Interests: Competing interests: MTK received research funds from NIHR RfPB, MRC CiC, GCRF, FSA and University of Birmingham outside this work. His department at UHB received educational grants for PracticAllergy Course from ALK Abello, Allergy Therapeutics, MEDA, Thermo Fisher Scientific and other pharmaceutical companies over the years. He is Chair of Equality, Diversity and Inclusion working group of BSACI, co-author for BSACI guidelines on penicillin allergy and an associate editor for Clinical Experimental Allergy. RD delivered paid consultancy services to Baxter medical. He has a salaried position as chief executive of UK Sepsis Trust. RB received funding or honoraria for conference attendance, Advisory boards, lectures and training from Pfizer and Menarini. Senior Editor for JAC-AMR (BSAC journal). NP is a NIHR/ HEE CDRF studying non-allergist penicillin allergy de-labelling in secondary care (Clinical Doctoral Research Fellowship). He is co-lead on the BSAC MOOC on non-allergist penicillin allergy de-labelling (British Society Antimicrobial Chemotherapy Massive Open Online Community). SAM is National Clinical Director for the Blood and Infection Programme of Care, NHS England. JATS has research funding from the NIHR and Wellcome Trust in relation to penicillin allergy. He is a member of the British Society for Allergy and Clinical Immunology allergy working party. He is co-lead on the BSAC MOOC on non-allergist penicillin allergy de-labelling (British Society Antimicrobial Chemotherapy Massive Open Online Community) and a BSAC council member., (© 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.)

In porous water filters, the transport and entrapment of contaminants can be modeled as a classic mass transport problem, which employs the conventional convection-dispersion equation to predict the transport of species existing in trace amounts. Using the volume-averaging method (VAM), the upscaling has revealed two possible macroscopic equations for predicting contaminant concentrations in the filters. The first equation is the classical convection-dispersion equation, which incorporates a total dispersion tensor. The second equation involves an additional transport coefficient, identified as the adsorption-induced vector. In this study, the aforementioned equations were solved in 1D for column tests using 3D unit cells. The simulated breakthrough curves (BTCs), using the proposed micro-macro-coupling-based VAM model, are compared with the direct numerical simulation (DNS) results based on BCC-type unit cells arranged one-after-another in a daisy chain manner, as well as with three previously reported experimental works, in which the functionalized zeolite and zero-valent iron fillings were used as an adsorbent to remove phosphorous and arsenic from water, respectively. The disagreement of VAM BTC predictions with DNS and experimental results reveals the need for an alternative closure formulation in VAM. Detailed investigations reveal time constraint violations in all the three cases, suggesting this as the main cause of VAM's failure.

Importance: Positive airway pressure (PAP) is the first-line treatment for obstructive sleep apnea (OSA), but evidence on its beneficial effect on major adverse cardiovascular events (MACE) and mortality prevention is limited., Objective: To determine whether PAP initiation and utilization are associated with lower mortality and incidence of MACE among older adults with OSA living in the central US., Design, Setting, and Participants: This retrospective clinical cohort study included Medicare beneficiaries with 2 or more distinct OSA claims identified from multistate, statewide, multiyear (2011-2020) Medicare fee-for-service claims data. Individuals were followed up until death or censoring on December 31, 2020. Analyses were performed between December 2021 and December 2023., Exposures: Evidence of PAP initiation and utilization based on PAP claims after OSA diagnosis., Main Outcomes and Measures: All-cause mortality and MACE, defined as a composite of myocardial infarction, heart failure, stroke, or coronary revascularization. Doubly robust Cox proportional hazards models with inverse probability of treatment weights were used to estimate treatment effect sizes controlling for sociodemographic and clinical factors., Results: Among 888 835 beneficiaries with OSA included in the analyses (median [IQR] age, 73 [69-78] years; 390 598 women [43.9%]; 8115 Asian [0.9%], 47 122 Black [5.3%], and 760 324 White [85.5%] participants; median [IQR] follow-up, 3.1 [1.5-5.1] years), those with evidence of PAP initiation (290 015 [32.6%]) had significantly lower all-cause mortality (hazard ratio [HR], 0.53; 95% CI, 0.52-0.54) and MACE incidence risk (HR, 0.90; 95% CI, 0.89-0.91). Higher quartiles (Q) of annual PAP claims were progressively associated with lower mortality (Q2 HR, 0.84; 95% CI, 0.81-0.87; Q3 HR, 0.76; 95% CI, 0.74-0.79; Q4 HR, 0.74; 95% CI, 0.72-0.77) and MACE incidence risk (Q2 HR, 0.92; 95% CI, 0.89-0.95; Q3 HR, 0.89; 95% CI, 0.86-0.91; Q4 HR, 0.87; 95% CI, 0.85-0.90)., Conclusions and Relevance: In this cohort study of Medicare beneficiaries with OSA, PAP utilization was associated with lower all-cause mortality and MACE incidence. Results might inform trials assessing the importance of OSA therapy toward minimizing cardiovascular risk and mortality in older adults.

Abstract: The immune revolution that swept the field of oncology in the mid-2010s with the advent of checkpoint inhibitors has led to a paradigm shift in approaches toward adapting new cancer prevention modalities. Cancer vaccines have emerged from this era with astounding potential as a durable intervention to prevent cancers especially for patients with hereditary susceptibilities such as Lynch syndrome carriers. This review covers new insights in the immunoprevention landscape for patients living with Lynch syndrome including highlights ranging from clinical trials exploring the use of chemoprevention agents to boost immune cellularity to investigative studies using novel vaccine approaches to induce long-term antitumor immunity., Competing Interests: Conflicts of Interest and Source of Funding: E.V. had a consulting or advisory role with Janssen Research and Development, Recursion Pharma, Guardant Health, Rising Tide Foundation, and Nouscom, s.r.l. He has received research support from Janssen Research and Development. This work was supported by grants CA260761 and CA257375 (US National Institutes of Health/National Cancer Institute) to E.V. For the remaining authors none were declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Loose bodies in the knee joint are relatively common and the common causes are transchondral fractures, synovial chondromatosis, osteochondritis dissecans, meniscal injury, and osteoarthritis. Neoplastic growths from synovium have been reported to have presentations mimicking loose bodies or meniscus tears., Case Report: We report the case of an unusual cause of loose body in the knee joint of a 35-year-old male who reported for follow-up 3 years after the surgical management of giant cell tumor (GCT) of the distal femur. He had symptoms of loose bodies in the joint without any complaint specific to the operative site. Imaging revealed loose bodies within the joint which were removed arthroscopically. Histopathology showed the loose bodies as GCT. The patient had relief of symptoms after removal and the patient has no evidence of recurrence at the primary site or in the knee joint., Conclusion: GCTs should be considered a cause of loose bodies in the joint when there is a neighboring bone affected by GCT and all such loose bodies removed should undergo histopathological examination., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)

Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.

Objectives: The primary objective was to determine normative values of oxygen saturation (SpO2) by pulse oximetry in apparently healthy children, aged 1 month to 14 years. The secondary objective was to explore any variation in oxygen saturation levels by age and gender., Materials and Methods: It was a cross-sectional study conducted at a tertiary care centre and schools in Bhubaneswar, Odisha, India, from January 2021 to December 2022. Apparently healthy children were enrolled. Using a standardized pulse oximeter and appropriately sized probes, SpO2 was recorded after stabilization of plethysmograph waves. Three consecutive readings were taken, and an average was noted. The 2.5th centile SpO2 value was taken as the lower limit of normal., Results: The median (IQR) saturation of the sample population was 99.7% (99-100). The 2.5th, 5th, 25th, and 75th percentiles were 97.7%, 98%, 99%, and 100%, respectively. Median SpO2 and its percentiles were estimated for each age group. The 2.5th centile SpO2 for infantile age group was 96.4%. No significant age and gender-wise variations of SpO2 were noted., Conclusions: The present study established normal reference range oxygen SpO2 levels in apparently healthy children from an eastern India region that is situated at 62 m (204 ft) above the sea level., (Copyright © 2024 Copyright: © 2024 Indian Chest Society.)

Cardiac channelopathies are a group of heritable disorders that affect the heart's electrical activity due to genetic variations present in genes coding for ion channels. With the advent of new sequencing technologies, molecular diagnosis of these disorders in patients has paved the way for early identification, therapeutic management and family screening. The objective of this retrospective study was to understand the efficacy of whole-genome sequencing in diagnosing patients with suspected cardiac channelopathies who were reported negative after whole exome sequencing and analysis. We employed a 3-tier analysis approach to identify nonsynonymous variations and loss-of-function variations missed by exome sequencing, and structural variations that are better resolved only by sequencing whole genomes. By performing whole genome sequencing and analyzing 25 exome-negative cardiac channelopathy patients, we identified 3 pathogenic variations. These include a heterozygous likely pathogenic nonsynonymous variation, CACNA1C:NM&#95;000719:exon19:c.C2570G:p. P857R, which causes autosomal dominant long QT syndrome in the absence of Timothy syndrome, a heterozygous loss-of-function variation CASQ2:NM&#95;001232.4:c.420+2T>C classified as pathogenic, and a 9.2 kb structural variation that spans exon 2 of the KCNQ1 gene, which is likely to cause Jervell-Lange-Nielssen syndrome. In addition, we also identified a loss-of-function variation and 16 structural variations of unknown significance (VUS). Further studies are required to elucidate the role of these identified VUS in gene regulation and decipher the underlying genetic and molecular mechanisms of these disorders. Our present study serves as a pilot for understanding the utility of WGS over clinical exomes in diagnosing cardiac channelopathy disorders., (© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Introduction: Burn registers are an important source of surveillance data on injury intent. These data are considered essential to inform prevention activities. In South Asia, intentional burn injuries are thought to disproportionately affect women. Assessment of injury intent is difficult because it is influenced by personal, family, social, and legal sensitivities. This can introduce misclassification into data, and bias analyses. We conducted a descriptive, hypothesis generating study to explore misclassification of injury intent using data from a newly digitised single centre burn register in south India., Methods: Data from 1st February 2016 to 28th February 2022 were analysed. All patients in the data set were included in the study (n = 1930). Demographic and clinical characteristics for patients are described for each classification of injury intent. All data cleaning and analyses were completed using RStudio., Results: Injury intent data were missing for 12.6% of cases. It was the most commonly missing variable in the data set. "Accidental" injuries had a similar distribution over time, age, and total body surface area (TBSA) for males and females. "Homicidal" injuries were more common in females. Injuries reported as "Suicidal" affected men and women equally. A decrease in reporting of "Suicidal" injuries in females corresponded to an increase in high TBSA injuries classified as 'Other' or with missing data. Overwriting of injury intent was present in 1.5% of cases. The overwritten group had a greater proportion of females (62.1% vs. 48.5%) and higher median TBSA (77.5% vs. 27.5%) compared to the group where intent was not overwritten., Conclusion: Our findings indicate that some subgroups, such as females with high TBSA burns, appear to be more likely to be misclassified and should be the focus of future research. They also highlight that quality of surveillance data could be improved by recording of clinical impression, change in patient reported intent, and use of a common data element for intent to standardise data collection. We also recommend that injury intent is recorded as a unique variable and should not be mixed with other elements of injury causation (e.g. mechanism). Although this is a single centre study, the methods will be of interest to those who utilise routinely collected data and wish to reduce misclassification of this important variable., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: The differential diagnosis of intrinsic nonfibrotic conditions that may lead to portal hypertension include hepatoportal sclerosis (HPS), nodular regenerative hyperplasia (NRH), and sinusoidal obstruction syndrome (SOS). In this article, we characterize the clinical features and outcome of these lesions when they manifest as portal hypertension. Methods: Data was collected through retrospective patient medical records. Results: Patients (HPS: 28, NRH: 17, SOS: 11) were identified more frequently in recent years. All groups presented with signs and symptoms of portal hypertension. All patients had complex medical histories. An elevated serum alkaline phosphatase occurred in all groups and an elevated bilirubin with SOS. Imaging of the liver with HPS and NRH suggested cirrhosis, which was not seen with SOS. 11%, 12%, and 9% of patients in the HPS, NRH, and SOS respectively, underwent transjugular intrahepatic portosystemic shunt placement to manage the complications of portal hypertension, while 43%, 24%, and 36% of patients respectively, received a liver transplant. Conclusions: Patients with HPS, NRH, and SOS had complex medical histories, likely contributing to the development of these lesions. They are recognized more frequently now. In contrast to HPS and NRH, SOS occurred in liver transplant recipients, was associated with elevated serum bilirubin, and imaging did not suggest the presence of advanced fibrosis/cirrhosis. Liver transplantation appeared to be a viable treatment for complications related to HPS and NRH. Retransplantation for SOS yielded mixed results. HPS, SOS, and NRH should be considered when evaluating liver specimens from patients with unexplained nonfibrotic portal hypertension. Key message: Intrinsic nonfibrotic causes of portal hypertension appear to be increasing in frequency. The differential diagnosis includes NRH, HPS, and SOS. These conditions are associated with complex diseases and possibly due to treatments. Pathologists need to be aware of this differential diagnosis when presented with liver biopsies performed to assess portal hypertension., 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.

Objective of the study was to find the association of vitamin D receptor (VDR) polymorphisms (Fokl, Taql and Apal) with vitamin D levels in diabetic foot ulcer (DFU) patients in South India. In this case-control study, plasma vitamin D levels and VDR genotype frequencies of 70 cases (DFU patients) were compared with 70 diabetic (diabetes mellitus [DM] [non-DFU]) patients and 70 apparently healthy controls (HC) from South India. Plasma vitamin D levels were measured using the ELISA technique, and genotyping of VDR polymorphisms was carried out using real-time polymerase chain reaction. Logistic regression was used to find the association between DFU versus HC and DFU versus DM traits. Association analysis was performed based on additive, dominant and recessive models with age and gender as covariates. A 45.7% of DFU patients have sufficient vitamin D levels than 48.6% and 40% of DM patients and HC, respectively. Linkage disequilibrium analysis for DFU versus HC and DFU versus DM traits shows that single nucleotide polymorphisms (SNPs) Taq1 (rs731236) and Apal (rs7975232) are in strong linkage disequilibrium in DFU patients. The alleles and genotype frequencies were similar in all three groups. Although the additive model does not show statistical significance, age and sex correlate with the three SNPs (Fokl, Taql and Apal). No association was found between VDR gene polymorphisms and vitamin D levels in DFU patients in Southern India. On the other hand, age and sex correlate with the three SNPs., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

The re-epithelialization process gets severely dysregulated in chronic nonhealing diabetic foot ulcers/wounds. Keratinocyte growth factor (KGF or FGF-7) is the major modulator of the re-epithelialization process, which regulates the physiological phenotypes of cutaneous keratinocytes. The existing therapeutic strategies of growth factor administration have several limitations. To overcome these, we have designed a KGF-mimetic peptide (KGFp, 13mer) based on the receptor interaction sites in murine KGF. KGFp enhanced migration and transdifferentiation of mouse bone marrow-derived MSCs toward keratinocyte-like cells (KLCs). A significant increase in the expression of skin-specific markers Bnc1 (28.5-fold), Ck5 (14.6-fold), Ck14 (26.1-fold), Ck10 (187.7-fold), and epithelial markers EpCam (23.3-fold) and Cdh1 (64.2-fold) was associated with the activation of ERK1/2 and STAT3 molecular signaling in the KLCs. Further, to enhance the stability of KGFp in the wound microenvironment, it was conjugated to biocompatible 3D porous polymer scaffolds without compromising its active binding sites followed by chemical characterization using Fourier transform infrared spectroscopy, field-emission scanning electron microscopy, dynamic mechanical analysis, and thermogravimetry. In vitro evaluation of the KGFp-conjugated 3D polymer scaffolds revealed its potential for transdifferentiation of MSCs into KLCs. Transplantation of allogeneic MSC GFP using KGFp-conjugated 3D polymer scaffolds in chronic nonhealing type 2 diabetic wounds ( db/db transgenic, 50-52 weeks old male mice) significantly enhanced re-epithelialization-mediated wound closure rate (79.3%) as compared to the control groups (Untransplanted -22.4%, MSC GFP -3D polymer scaffold -38.5%). Thus, KGFp-conjugated 3D porous polymer scaffolds drive the fate of the MSCs toward keratinocytes that may serve as potential stem cell delivery platform technology for tissue engineering and transplantation.

Major research interests on quantum key distribution (QKD) are primarily focused on increasing 1. Point-to-point transmission distance (1000 km). 2. Secure key rate (Mbps). 3. Security of quantum layer (device-independence). It is great to push the boundaries in these fronts but these isolated approaches are neither scalable nor cost-effective due to requirements of specialised hardware and different infrastructure. Current and future QKD network requires addressing different set of challenges apart from distance, key rate and quantum security. In this regard, we present ChaQra-a sub quantum network with core features as 1. Crypto agility (integration in the already deployed telecommunication fibres). 2. Software defined networking (SDN paradigm for routing different nodes). 3. reliability (addressing denial-of-service with hybrid quantum safe cryptography). 4. upgradability (modules upgradation based on scientific and technological advancements). 5. Beyond QKD (using QKD network for distributed computing, multi-party computation etc). Our results demonstrate a clear path to create and accelerate quantum secure Indian subcontinent under national quantum mission., (© 2024. The Author(s).)

Here, we employ polymer physics models of chromatin to investigate the 3D folding of a 2Mb wide genomic region encompassing the human LTN1 gene, a crucial DNA locus involved in key cellular functions. Through extensive Molecular Dynamics simulations, we reconstruct in-silico the ensemble of single-molecule LTN1 3D structures, which we benchmark against recent in-situ Hi-C 2.0 data. The model-derived single molecules are then used to predict structural folding features at the single-cell level, providing testable predictions for super-resolution microscopy experiments., Competing Interests: COMPETING INTERESTS J.D. is a member of the scientific advisory board of Arima Genomics, San Diego, CA, USA and Omega Therapeutic, Cambridge, MA, USA.

Introduction The primary goal of endodontic therapy is to achieve a three-dimensional filling of the root canal. The sealer plays a crucial role in filling the residual gaps between the gutta-percha and the canal wall, which prevents fluids and bacteria from entering the canal and causing complications. This study evaluates and compares the sealing ability of four root canal sealers to the root dentin. Methods and materials In this study, forty single-rooted mandibular premolar teeth with fully-formed apices were collected. The teeth were decoronated and instrumented. Later, the teeth were randomly divided into four groups, each comprising ten specimens, based on the sealer used for obturation. The first group was obturated with BioRoot RCS (Septodont, Septodont Holding, Paris, France), the second group with MTA-Fillapex (Angelus, Angelus Indústria de Produtos Odontológicos S/A, Brazil), the third group with EpoxySeal (Safe Endo, SafeEndo Dental India Pvt. Ltd., Gujarat, India), and the fourth group with Sealapex (Kerr, Kerr Corporation, Brea, CA). Following obturation, the teeth were sectioned vertically using a diamond disc, and the marginal adaptation of these sealers to the root dentin was assessed using scanning electron microscopy (SEM). The values were then statistically analyzed. Results EpoxySeal showed the maximum amount of marginal adaptation (5.22±0.47), followed by BioRoot RCS (5.48±0.58) and MTA-Fillapex (8.24±0.74), and the least amount of marginal adaptation was shown by Sealapex (11.64±1.35). Based on the analysis of variance (ANOVA), a statistically significant difference (p≤0.001) was observed. According to Tukey's post hoc test, the mean difference between all groups showed statistical significance (p≤0.05) except between BioRoot RCS and EpoxySeal. Conclusion Within the limitations of this in vitro study, it is concluded that EpoxySeal and BioRoot RCS exhibited superior marginal adaptation to the root dentin. BioRoot RCS can be recommended as a sealer of choice owing to its additional properties, such as antimicrobial and hydrophilic affinity during setting., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kirthiga et al.)

Background: Several factors shape the neurodevelopmental trajectory. A key area of focus in neurodevelopmental research is to estimate the factors that have maximal influence on the brain and can tip the balance from typical to atypical development., Methods: Utilizing a dissimilarity maximization algorithm on the dynamic mode decomposition (DMD) of the resting state functional MRI data, we classified subjects from the cVEDA neurodevelopmental cohort ( n = 987, aged 6-23 years) into homogeneously patterned DMD (representing typical development in 809 subjects) and heterogeneously patterned DMD (indicative of atypical development in 178 subjects)., Results: Significant DMD differences were primarily identified in the default mode network (DMN) regions across these groups ( p < 0.05, Bonferroni corrected). While the groups were comparable in cognitive performance, the atypical group had more frequent exposure to adversities and faced higher abuses ( p < 0.05, Bonferroni corrected). Upon evaluating brain-behavior correlations, we found that correlation patterns between adversity and DMN dynamic modes exhibited age-dependent variations for atypical subjects, hinting at differential utilization of the DMN due to chronic adversities., Conclusion: Adversities (particularly abuse) maximally influence the DMN during neurodevelopment and lead to the failure in the development of a coherent DMN system. While DMN's integrity is preserved in typical development, the age-dependent variability in atypically developing individuals is contrasting. The flexibility of DMN might be a compensatory mechanism to protect an individual in an abusive environment. However, such adaptability might deprive the neural system of the faculties of normal functioning and may incur long-term effects on the psyche.

Topic Importance: Laryngeal dysfunction as a cause of chronic refractory cough and episodic dyspnea is often missed, which results in unnecessary testing and delays in diagnosis. Understanding laryngeal roles in breathing and airway protection can help to appreciate the propensity to laryngeal dysfunction with aging, chronic lung disease, and sleep apnea., Review Findings: The human larynx is a complex muscular structure that is responsible for multiple roles of breathing, vocalization, coughing, and swallowing. To undertake these activities, the larynx has a high density of sensory and motor innervation. In addition to common embryological origins with the pharynx and esophagus, with which many laryngeal activities are shared, somatomotor and autonomic pathways regulate emotional, cognitive, and complex motor sequence-planning activities within the larynx. Due to its unique location, the larynx is susceptible to infectious and gastroesophageal reflux-related insults. Couple this with key roles in regulation of airflow and mediation of airway protective reflexes, it is not surprising that neuropathic abnormalities and muscle dysfunction frequently develop. The expression of laryngeal dysfunction as hypersensitivity to mechanical, thermal, chemical, and other stimuli leads to exaggerated airway protective reflexes (laryngeal adductor reflex and cough reflex) manifesting as dyspnea and cough., Summary: Pulmonologists should incorporate assessment of laryngeal dysfunction during evaluation of chronic refractory cough and dyspnea. Recognition of laryngeal hypersensitivity in the patient with chronic refractory cough can identify patients who may benefit from cough suppression therapies. Similarly, timely identification of inducible laryngeal obstruction may not only resolve episodic dyspnea but lessen the need for unnecessary testing and treatments., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: K. M. S. reports a relationship with Hypnoscure LLC that includes board membership; and has served as past consultant for Merck Inc. and ResMed Inc. M. J. M. reports a relationship with Janssen Pharmaceuticals Inc. that includes speaking and lecture fees. None declared (A. S.)., (Published by Elsevier Inc.)

While TGF-β signaling is essential for microglial function, the cellular source of TGF-β1 ligand and its spatial regulation remains unclear in the adult CNS. Our data supports that microglia but not astrocytes or neurons are the primary producers of TGF-β1 ligands needed for microglial homeostasis. Microglia-Tgfb1 KO leads to the activation of microglia featuring a dyshomeostatic transcriptome that resembles disease-associated, injury-associated, and aged microglia, suggesting microglial self-produced TGF-β1 ligands are important in the adult CNS. Astrocytes in MG-Tgfb1 inducible (i)KO mice show a transcriptome profile that is closely aligned with an LPS-associated astrocyte profile. Additionally, using sparse mosaic single-cell microglia KO of TGF-β1 ligand we established an autocrine mechanism for signaling. Here we show that MG-Tgfb1 iKO mice present cognitive deficits, supporting that precise spatial regulation of TGF-β1 ligand derived from microglia is required for the maintenance of brain homeostasis and normal cognitive function in the adult brain., (© 2024. The Author(s).)

After sporadic reports of post-treatment control of HIV in children who initiated combination anti-retroviral therapy (cART) early, we prospectively studied 284 very-early-cART-treated children from KwaZulu-Natal, South Africa, after vertical HIV transmission to assess control of viremia. Eighty-four percent of the children achieved aviremia on cART, but aviremia persisting to 36 or more months was observed in only 32%. We observed that male infants have lower baseline plasma viral loads (P = 0.01). Unexpectedly, a subset (n = 5) of males maintained aviremia despite unscheduled complete discontinuation of cART lasting 3-10 months (n = 4) or intermittent cART adherence during 17-month loss to follow-up (n = 1). We further observed, in vertically transmitted viruses, a negative correlation between type I interferon (IFN-I) resistance and viral replication capacity (VRC) (P < 0.0001) that was markedly stronger for males than for females (r = -0.51 versus r = -0.07 for IFN-α). Although viruses transmitted to male fetuses were more IFN-I sensitive and of higher VRC than those transmitted to females in the full cohort (P < 0.0001 and P = 0.0003, respectively), the viruses transmitted to the five males maintaining cART-free aviremia had significantly lower replication capacity (P < 0.0001). These data suggest that viremic control can occur in some infants with in utero-acquired HIV infection after early cART initiation and may be associated with innate immune sex differences., (© 2024. The Author(s).)

Background: Timely and accurate screening of malnutrition at the community level is essential to identifying malnourished children. The World Health Organization (WHO) guidelines classify non-oedematous acute malnutrition among children using mid-upper arm circumference (MUAC) or weight-for-height Z-score (WHZ). Study Design: A cross-sectional study., Methods: This study was conducted among children aged 6‒60 months. After necessary exclusions, 433 participants were selected using a multi-stage simple random sampling method. Using WHO guidelines for global acute malnutrition (GAM) [WHZ<-2, MUAC<12.5 cm], the sensitivity (Se), specificity (Sp), predictive values, likelihood ratios, Youden index, and receiver operating characteristic (ROC) curve were calculated for MUAC using WHZ as the criterion., Results: Out of 433 participants, 30% were diagnosed with GAM using WHZ, while 17.6% were found malnourished using MUAC measurements. As per WHO cut-offs, the Se, Sp, positive predictive value (PPV), negative predictive value (NPV), Youden index, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) of MUAC were 48%, 96%, 83%, 81%, 0.44, 12, and 0.54, respectively. The ROC curve displayed an area under the curve of 0.86 (95% confidence interval=0.83, 0.90) for MUAC<12.5 cm. Bivariate Pearson correlation also demonstrated a positive linear relationship (R2=0.302) between the WHZ and MUAC variables., Conclusion: Based on the findings, 48% of the children were correctly identified by the MUAC with an 83% probability of GAM (PPV=0.83). Moreover, there was 96% Sp in non-malnourished children, with only 4% false positives. Therefore, personnel at the grassroots level can use MUAC for timely and accurate screening of children in Anganwadi centers (AWCs) due to its ease of use and simplicity., (© 2024 The Author(s); Published by Hamadan University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

HIV is a disease which reduces human resistant to fight. When our immunity becomes so weak that we are not able to fight even the common commensals of our body, this leads to what is called as an opportunistic infection. Tuberculosis is one of those most common type of opportunistic infection and in this pulmonary tuberculosis is more common. Extrapulmonary tuberculosis with HIV is the area of lesser research. In this study we tried to prove the Prevalence of extrapulmonary tuberculosis in AIDS patients and also the effect of combined HAART and ATT on prevalence of extrapulmonary tuberculosis and also its effect on Quality of life of the patient. This is a retrospective study conducted in a tertiary centre in the Department of Otorhinolaryngology & head and neck surgery from January 2020 to December 2020. A total of 80 patients were studied for 1 year. Confirmed cases of AIDS with extra pulmonary tuberculosis in head and neck region were studied, keeping all ethical issues in mind and after complete treatment of ATT along with HAART. After treatment, a significant number of patients got resolved with EPTB and gave positive response on their quality of life. Not only pulmonary tuberculosis, extrapulmonary tuberculosis with HIV is on the rise nowadays. Combined treatment of both can help in decreasing prevalence of extrapulmonary tuberculosis and improves quality of life., Competing Interests: Conflict of interestAuthors announced, there is no conflict of interest., (© Association of Otolaryngologists of India 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

An emerging body of literature describes the prevalence and consequences of hypercapnic respiratory failure. While device qualifications, documentation practices, and previously performed clinical studies often encourage conceptualizing patients as having a single "cause" of hypercapnia, many patients encountered in practice have several contributing conditions. Physiologic and epidemiologic data suggest that sleep-disordered breathing-particularly obstructive sleep apnea (OSA)-often contributes to the development of hypercapnia. In this review, the authors summarize the frequency of contributing conditions to hypercapnic respiratory failure among patients identified in critical care, emergency, and inpatient settings with an aim toward understanding the contribution of OSA to the development of hypercapnia., Competing Interests: Disclosure B.W. Locke. receives research funding from the American Thoracic Society ASPIRE Fellowship and the National Institutes of Health under the Ruth L. Kirschstein National Research Service Award 5T32HL105321 J.P. Brown. no conflicts of interest. K.M. Sundar is co-founder of Hypnoscure LLC—a software application for population management of sleep apnea through the University of Utah Technology Commercialization Office., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Chronic cough, defined as a cough lasting more than 8 weeks, is a common medical condition occurring in 5% to 10% of the population. Its overlap with another highly prevalent disorder, obstructive sleep apnea (OSA), is therefore not surprising. The relationship between chronic cough and OSA extends beyond this overlap with higher prevalence of OSA in patients with chronic cough than in the general population. The use of continuous positive airway pressure can result in improvement in chronic cough although further studies are needed to understand which patients will experience benefit in their cough from the treatment of comorbid OSA., Competing Interests: Disclosures K.M. Sundar has served as consultant in the past for Merck Inc. He is a cofounder of Hypnoscure LLC (software for population management of sleep apnea) in conjuction with the University of Utah Technology Commercialization Office. A.C. Stark has no conflicts to disclose. P. Dicpinigaitis serves as a consultant to Bellus, Chiesi, GSK, Merck, Trevi., (Published by Elsevier Inc.)

There is an increased chance of further periodontal deterioration due to severe intrabony defect. There are s different patho physiologies for perio-endo lesions, ranging from quite basic to rather complicated but to make the right diagnosis, one must be aware of various illness processes also a careful history taking, examination, and the application of specialized tests can help achieve this. Each form of endodontic-periodontal illness has a different prognosis and course of therapy and all kinds of endo-perio lesions require endodontic and periodontal treatments are necessary for primary periodontal disease with subsequent endodontic involvement and real mixed endodontic-periodontal disorders. The severity of the periodontal disease and how well the patient responds to therapy will determine how these situations turn out. Because autologous platelet concentrates are enriched with growth factors, such as concentrated growth factor (CGF), they may enhance surgical outcomes. CGF is inserted into the appropriate intrabony defect following traditional flap debridement. Following flap surgery, the tooth in question had a root canal operation. Volumetric analysis was performed on both groups before to surgery and nine months after the procedure. It has been discovered that the defect area has a much larger bone volume due to the high levels of CGF, a regenerative and reconstructive growth factor that promotes early and high bone fill., Competing Interests: There are none, (© 2024 Biomedical Informatics.)

Background: Microsatellite instability (MSI) secondary to mismatch repair (MMR) deficiency is characterized by insertions and deletions (indels) in short DNA sequences across the genome. These indels can generate neoantigens, which are ideal targets for precision immune interception. However, current neoantigen databases lack information on neoantigens arising from coding microsatellites. To address this gap, we introduce The MicrOsatellite Neoantigen Discovery Tool (MONET)., Method: MONET identifies potential mutated tumor-specific neoantigens (neoAgs) by predicting frameshift mutations in coding microsatellite sequences of the human genome. Then MONET annotates these neoAgs with key features such as binding affinity, stability, expression, frequency, and potential pathogenicity using established algorithms, tools, and public databases. A user-friendly web interface (https://monet.mdanderson.org/) facilitates access to these predictions., Results: MONET predicts over 4 million and 15 million Class I and Class II potential frameshift neoAgs, respectively. Compared to existing databases, MONET demonstrates superior coverage (>85% vs. <25%) using a set of experimentally validated neoAgs., Conclusion: MONET is a freely available, user-friendly web tool that leverages publicly available resources to identify neoAgs derived from microsatellite loci. This systems biology approach empowers researchers in the field of precision immune interception., Competing Interests: EV has a consulting or advisory role with Janssen Research and Development, Recursion Pharma, Guardant Health, The Rising Tide Foundation, and Nouscom, s.r.l. EV has received research support from Janssen Research and Development. The remaining 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 Deng, Sinha and Vilar.)

Waste segregation is an essential aspect of a smoothly functioning waste management system. Usually, various recyclable waste types are disposed of together at the source, and this brings in the necessity to segregate them into their categories. Dry waste needs to be separated into its own categories to ensure that the proper procedures are implemented to treat and process it, which leads to an overall increased recycling rate and reduced landfill impact. Paper, plastics, metals, and glass are just a few examples of the many dry waste materials that can be recycled or recovered to create new goods or energy. Over the past years, much research has been conducted to devise effective and productive ways to achieve proper segregation for the waste that is being produced at an ever-increasing rate. This article introduces a multi-class garbage segregation system employing the YOLOv5 object detection model. Our final prototype demonstrates the capability of classifying dry waste categories and segregating them into their respective bins using a 3D-printed robotic arm. Within our controlled test environment, the system correctly segregated waste classes, mainly paper, plastic, metal, and glass, eight out of 10 times successfully. By integrating the principles of artificial intelligence and robotics, our approach simplifies and optimizes the traditional waste segregation process., Competing Interests: The authors declare there are no competing interests., (©2024 Lahoti et al.)

Background and objective Human rhinovirus (HRV) is one of the leading causes of pediatric respiratory tract infection with a prevalence rate of 30-50%, mostly affecting children below five years of age and causing a substantial amount of economic loss. In children, it can alone or as a co-infection, cause a wide range of symptoms from mild to life-threatening ones. With the above background, the current study was carried out to emphasize the role of HRV mono-infection in pediatric acute respiratory tract infections by correlating clinical and molecular laboratory findings. Methods This study was carried out in a tertiary care teaching hospital over a duration of four years (March 2019-October 2023). Children up to 14 years of age visiting the outpatient department or admitted to the ward with diagnoses of acute respiratory tract infections (ARTIs) were included. The clinical and laboratory data were retrieved and analyzed. A nasopharyngeal swab (NPS) or throat swab (TS) was collected and sent to the Microbiology laboratory maintaining the cold chain. Nucleic acid was extracted and subjected to multiplex real-time polymerase chain reaction (RT-PCR). Result Of the 245 samples tested for the respiratory viral pathogen, 52 samples tested positive for HRV, of which 27 had HRV mono-infection. The clinico-demographic details of these 27 patients were studied in detail. The majority of the cases (24/27; 88.8%) were less than five years of age. Fever and shortness of breath were the most consistent symptoms in all. Nineteen (19/27; 62.9%) HRV mono-infection cases had underlying co-morbidities, all requiring respiratory support. The HRV mono-infection cases either developed bronchiolitis, lower respiratory tract infection, or pneumonia. All mono-infection cases had cycle threshold value (Ct) < 25, while the Ct value of HRV was > 30 in co-infection with other viruses. Conclusion Mono-infection of HRV in under-five children with underlying comorbidities and a lesser Ct value indicates severe disease manifestation and should be dealt with more cautiously., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Mohanty et al.)

Background: Inflammatory bowel disease (IBD) is associated with increased health care utilization. Forecasting of high resource utilizers could improve resource allocation. In this study, we aimed to develop machine learning models (1) to cluster patients according to clinical utilization patterns and (2) to predict longitudinal utilization patterns based on readily available baseline clinical characteristics., Methods: We conducted a retrospective study of adults with IBD at 2 academic centers between 2015 and 2021. Outcomes included different clinical encounters, new prescriptions of corticosteroids, and initiation of biologic therapy. Machine learning models were developed to characterize health care utilization. Poisson regression compared frequencies of clinical encounters., Results: A total of 1174 IBD patients were followed for more than 5673 12-month observational windows. The clustering method separated patients according to low, medium, and high resource utilizers. In Poisson regression models, compared with low resource utilizers, moderate and high resource utilizers had significantly higher rates of each encounter type. Comparing moderate and high resource utilizers, the latter had greater utilization of each encounter type, except for telephone encounters and biologic therapy initiation. Machine learning models predicted longitudinal health care utilization with 81% to 85% accuracy (area under the receiver operating characteristic curve 0.84-0.90); these were superior to ordinal regression and random choice methods., Conclusion: Machine learning models were able to cluster individuals according to relative health care resource utilization and to accurately predict longitudinal resource utilization using baseline clinical factors. Integration of such models into the electronic medical records could provide a powerful semiautomated tool to guide patient risk assessment, targeted care coordination, and more efficient resource allocation., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. 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.)

Impacts of river discharge on coastal ocean processes are multi-dimensional. Studies on sinking particle fluxes, composition and their seasonal variability in coastal oceans are very limited. In this study, we investigated the impact of river discharge on seasonal variability in sinking fluxes of total mass, biogenic and lithogenic material in a river-dominated continental margin, western coastal Bay of Bengal. Higher POC, lithogenic and total mass fluxes were found during early southwest monsoon, and are decoupled with peak river discharge and elevated primary production. It is attributed to cross-shelf transport of re-suspended surface sediments from shelf region. Peak river discharge followed by elevated chlorophyll-a suggest nutrients supply though river discharge support primary production. Elemental C:N ratios, δ 13 C and δ 15 N results likely suggest that both marine and terrestrial sources contributed to sinking POM, . Overall, higher sinking fluxes during southwest monsoon than rest of the year suggest that seasonal river discharge exerts considerable impact on sinking fluxes in the western coastal Bay of Bengal., 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 Elsevier Ltd. All rights reserved.)

Metals are essential at trace levels to aquatic organisms for the function of many physiological and biological processes. But their elevated levels are toxic to the ecosystem and even brings about shifts in the plankton population. Threshold limits such as Predicted No Effect Concentration (PNEC - 0.6 μg/l of Cd; 2.7 μg/l of Pb), Criterion Continuous Concentration (CCC - 3.0 μg/l of Cd; 4.5 μg/l of Pb) and Criterion Maximum Concentration (CMC - 23 μg/l of Cd; 130 μg/l of Pb) prescribed for Indian coastal waters were used for the study. Short-term mesocosm experiments (96 h) were conducted in coastal waters of Visakhapatnam to evaluate responses of the planktonic community on exposure to threshold concentrations of cadmium and lead for the first time. Four individual experimental bags of 2500 L capacity (Control, PNEC, CCC & CMC) were used for the deployment and ambient water samples were analysed simultaneously to evaluate the impacts of the threshold levels in the natural waters. Chaetoceros sp. were dominant group in the control system whereas, Prorocentrum sp. Ceratium sp. Tintinopsis sp. Chaetoceros sp. and Skeletonema sp. were major groups in the test bags. Throughout the experiment the phytoplankton community did not show any significant differences with increased nutrients and plankton biomass (Chl-a <8.64 mg/m 3 ). Positive response of plankton community was observed in the experimental bags. High abundance of diatoms were observed in PNEC, CCC & CMC bags at 48 h and the abundance decreased with shift in the species at 72-96 h. The catalase activity in phytoplankton (5.99 nmol/min/ml) and the zooplankton (4.77 nmol/min/ml) showed induction after exposure to PNEC. The present mesocosm study is confirmed that short-term exposure to threshold metal concentration did not affects the phytoplankton community structure in PNEC, but CCC and CMC affects the community structure beyond 24 h. The insights from this study will serve as a baseline information and help develop environmental management tools. We believe that long-term mesocosm experiments would unravel metal detoxification mechanisms at the cellular level and metal transfer rate at higher trophic levels in real-world environment., 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 Elsevier Ltd. All rights reserved.)

Cervical cancer remains a significant global health burden, necessitating innovative approaches for improved diagnostics and personalized treatment strategies. Precision medicine has emerged as a promising paradigm, leveraging biomarkers and molecular targets to tailor therapy to individual patients. This review explores the landscape of emerging biomarkers and molecular targets in cervical cancer, highlighting their potential implications for precision medicine. By integrating these biomarkers into comprehensive diagnostic algorithms, clinicians can identify high-risk patients at an earlier stage, enabling timely intervention and improved patient outcomes. Furthermore, the identification of specific molecular targets has paved the way for the development of targeted therapies aimed at disrupting key pathways implicated in cervical carcinogenesis. In conclusion, the evolving landscape of biomarkers and molecular targets presents exciting opportunities for advancing precision medicine in cervical cancer. By harnessing these insights, clinicians can optimize treatment selection, enhance patient outcomes, and ultimately transform the management of this devastating disease., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier B.V.)

Isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) are two commonly used methods to probe biomolecular interactions. ITC can provide information about the binding affinity, stoichiometry, changes in Gibbs free energy, enthalpy, entropy, and heat capacity upon binding. SPR can provide information about the association and dissociation kinetics, binding affinity, and stoichiometry. Both methods can determine the nature of protein-protein interactions and help understand the physicochemical principles underlying complex biochemical pathways and communication networks. This methods article discusses the practical knowledge of how to set up and troubleshoot these two experiments with some examples., 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 Elsevier Inc. All rights reserved.)

Background & Aims: Lynch syndrome (LS) carriers develop mismatch repair-deficient neoplasia with high neoantigen (neoAg) rates. No detailed information on targetable neoAgs from LS precancers exists, which is crucial for vaccine development and immune-interception strategies. We report a focused somatic mutation and frameshift-neoAg landscape of microsatellite loci from colorectal polyps without malignant potential (PWOMP), precancers, and early-stage cancers in LS carriers., Methods: We generated paired whole-exome and transcriptomic sequencing data from 8 colorectal PWOMP, 41 precancers, 8 advanced precancers, and 12 early-stage cancers of 43 LS carriers. A computational pipeline was developed to predict, rank, and prioritize the top 100 detected mutated neoAgs that were validated in vitro using ELISpot and tetramer assays., Results: Mutation calling revealed >10 mut/Mb in 83% of cancers, 63% of advanced precancers, and 20% of precancers. Cancers displayed an average of 616 MHC-I neoAgs/sample, 294 in advanced precancers, and 107 in precancers. No neoAgs were detected in PWOMP. A total of 65% of our top 100 predicted neoAgs were immunogenic in vitro, and were present in 92% of cancers, 50% of advanced precancers, and 29% of precancers. We observed increased levels of naïve CD8 + and memory CD4 + T cells in mismatch repair-deficient cancers and precancers via transcriptomics analysis., Conclusions: Shared frameshift-neoAgs are generated within unstable microsatellite loci at initial stages of LS carcinogenesis and can induce T-cell responses, generating opportunities for vaccine development, targeting LS precancers and early-stage cancers., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Historically, investigators have not differentiated between patients with and without hemorrhagic transformation (HT) in large core ischemic stroke at risk for life-threatening mass effect (LTME) from cerebral edema. Our objective was to determine whether LTME occurs faster in those with HT compared to those without. We conducted a two-center retrospective study of patients with ≥ 1/2 MCA territory infarct between 2006 and 2021. We tested the association of time-to-LTME and HT subtype (parenchymal, petechial) using Cox regression, controlling for age, mean arterial pressure, glucose, tissue plasminogen activator, mechanical thrombectomy, National Institute of Health Stroke Scale, antiplatelets, anticoagulation, temperature, and stroke side. Secondary and exploratory outcomes included mass effect-related death, all-cause death, disposition, and decompressive hemicraniectomy. Of 840 patients, 358 (42.6%) had no HT, 403 (48.0%) patients had petechial HT, and 79 (9.4%) patients had parenchymal HT. LTME occurred in 317 (37.7%) and 100 (11.9%) had mass effect-related deaths. Parenchymal (HR 8.24, 95% CI 5.46-12.42, p < 0.01) and petechial HT (HR 2.47, 95% CI 1.92-3.17, p < 0.01) were significantly associated with time-to-LTME and mass effect-related death. Understanding different risk factors and sequelae of mass effect with and without HT is critical for informed clinical decisions., (© 2024. The Author(s).)

The fabrication of shape-selective coinage metal nanoclusters (MNCs) has promising applications due to their exceptional physical and chemical molecule-like properties. However, the stability of the specific geometry of the nanoclusters, such as their cubic shapes, is unclear and has been unraveled by assessing the nanoclusters' interactions with different environments. In this work, we investigate the morphological stability of cubic structured, coinage metal nanoclusters of varying sizes ranging from 14 to 1099 atoms. The impact of solvent environments like water and the presence of ionic liquids (IL) on the stabilization of the MNCs were assessed using molecular dynamics (MD) simulations. In general, smaller MNCs composed of less than 256 atoms encountered structural distortion easily compared to the larger ones, which preserved their cubic morphology with minimal surface aberrations in water. However, in the presence of 4M 1-butyl-1,1,1-trimethyl ammonium methane sulfonate [N1114][C1SO3] IL solution, the overall cubic shape of the MNCs was successfully preserved. Strikingly, it is observed that in contrast to the noble MNCs like Au and Ag, the cubic morphology for Cu MNCs with sizes less than 256 atoms exhibited significant stability even in the absence of IL.

Introduction: Endoscopic eradication therapy (EET) is standard of care for T1a esophageal adenocarcinoma (EAC). However, data on outcomes in high-risk T1a EAC are limited. We assessed and compared outcomes after EET of low-risk and high-risk T1a EAC, including intraluminal EAC recurrence, extraesophageal metastases, and overall survival., Methods: Patients who underwent EET for T1a EAC at 3 referral Barrett's esophagus endotherapy units between 1996 and 2022 were included. Patients with submucosal invasion, positive deep margins, or metastases at initial diagnosis were excluded. High-risk T1a EAC was defined as T1a EAC with poor differentiation and/or lymphovascular invasion, with low-risk disease being defined without these features. All pathology was systematically assessed by expert gastrointestinal pathologists. Baseline and follow-up endoscopy and pathology data were abstracted. Time-to-event analyses were performed to compare outcomes between groups., Results: One hundred eighty-eight patients with T1a EAC were included (high risk, n = 45; low risk, n = 143) with a median age of 70 years, and 84% were men. Groups were comparable for age, sex, Barrett's esophagus length, lesion size, and EET technique. Rates of delayed extraesophageal metastases (11.1% vs 1.4%) were significantly higher in the high-risk group ( P = 0.02). There was no significant difference in the rates of intraluminal EAC recurrence ( P = 0.79) and overall survival ( P = 0.73) between the 2 groups., Discussion: Patients with high-risk T1a EAC undergoing successful EET had a substantially higher rate of extraesophageal metastases compared with those with low-risk T1a EAC on long-term follow-up. These data should be factored into discussions with patients while selecting treatment approaches. Additional prospective data in this area are critical., (Copyright © 2023 by The American College of Gastroenterology.)