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Purpose: To compare T1 and T2 measurements across commercial and prototype 0.55T MRI systems in both phantom and healthy participants using the same vendor-neutral pulse sequences, reconstruction, and analysis methods., Methods: Standard spin echo measurements and abbreviated protocol measurements of T1, B1, and T2 were made on two prototype 0.55 T systems and two commercial 0.55T systems using an ISMRM/NIST system phantom. Additionally, five healthy participants were imaged at each system using the abbreviated protocol for T1, B1, and T2 measurement. The phantom measurements were compared to NMR-based reference measurements to determine accuracy, and both phantom and in vivo measurements were compared to assess reproducibility and differences between the prototype and commercial systems., Results: Vendor-neutral sequences were implemented across all four systems, and the code for pulse sequences and reconstruction is freely available. For participants, there was no difference in the mean T1 and T2 relaxation times between the prototype and commercial systems. In the phantom, there were no significant differences between the prototype and commercial systems for T1 and T2 measurements using the abbreviated protocol., Conclusion: Quantitative T1 and T2 measurements at 0.55T in phantom and healthy participants are not statistically different across the prototype and commercial systems., (© 2024 International Society for Magnetic Resonance in Medicine. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

The physiological consequences of environment-induced heat stress (EIHS), caused by prolonged exposure to excess heat and humidity, are largely unknown. The purpose of this investigation was to determine the extent to which EIHS alters cardiac health. We hypothesized that 24 h of EIHS would cause cardiac injury and cellular dysfunction in a murine EIHS model. To test this hypothesis, 7 wk old female mice were housed under thermoneutral (TN) conditions (n=12, 31.2 ± 1.01 °C, 35 ± 0.7% humidity) or EIHS conditions (n=14; 37.6 ± 0.01 °C, 42.0 ± 0.06 % humidity) for 24 h. Environment-induced heat stress increased rectal temperature by 2.1 °C ( P < 0.01) and increased subcutaneous temperature by 1.8 °C ( P < 0.01). Body weight was decreased by 10% ( P= 0.03), heart weight/body weight was increased by 26% ( P <0.01), and tissue water content was increased by 11% (P<0.05) in EIHS compared to TN. In comparison to TN, EIHS increased protein abundance of heat shock protein (HSP) 27 by 84% ( P =0.01); however, HSPs 90, 60, 70, and phosphorylated HSP 27 were similar between groups. Histological inspection of the heart revealed EIHS animals had increased myocyte vacuolation in left ventricle ( P =0.01), right ventricle ( P <0.01), and septum ( P =0.01) compared to TN animals. Biochemical indices are suggestive of mitochondrial remodeling, increased autophagic flux, and robust activation of endoplasmic reticulum stress in hearts from EIHS mice compared to TN mice. These data demonstrate that 1 d of EIHS is sufficient to induce myocardial injury and biochemical dysregulation.

Endoplasmic reticulum (ER) stress induces the repression of protein synthesis throughout the cell. Attempts to understand how localized stress leads to widespread repression have been limited by difficulties in resolving translation rates at the subcellular level. Here, using live-cell imaging of reporter mRNA translation, we unexpectedly found that during ER stress, active translation at mitochondria was significantly protected. The mitochondrial protein ATPase family AAA domain-containing protein 3A (ATAD3A) interacted with protein kinase RNA-like endoplasmic reticulum kinase (PERK) and mediated this effect on localized translation by competing for binding with PERK's target, eukaryotic initiation factor 2 (eIF2). PERK-ATAD3A interactions increased during ER stress, forming mitochondria-ER contact sites. Furthermore, ATAD3A binding attenuated local PERK signaling and rescued the expression of some mitochondrial proteins. Thus, PERK-ATAD3A interactions can control translational repression at a subcellular level, mitigating the impact of ER stress on the cell.

Ketoesterification stands as a pivotal technique in organic synthesis, particularly due to its essential role in the construction of numerous natural products and bioactive compounds. In this study, we have successfully accomplished a visible-light-induced cyclization and diastereoselective direct ketoesterification of cyclohexadienones, facilitating access to cis 6,5-fused tetrahydrobenzofuranone derivatives. The utilization of TEMPO radical quenching experiments has provided insights, suggesting an ionic mechanism underlying this methodology. Additionally, the regioselective addition of 2-oxo-2-phenylacetate to the least hindered side in a cis-selective fashion makes this protocol more appealing toward natural product development. Incorporation of a continuous flow reaction into the batch protocol has notably bolstered the efficiency and reaction rate. Furthermore, the demonstration of gram-scale reactions in the flow setup and synthetic utility with NaOH underscore the scalability and practical applicability of this approach.

Purpose: There is a longstanding belief that prostaglandin analogs (PGAs) may predispose patients with glaucoma to develop acute cystoid macular edema (CME). However, there is little solid evidence supporting this notion. The purpose of this study is to compare CME incidence rates among patients initiating treatment with different glaucoma medication classes., Design: Database study., Participants: 39948 patients who were newly prescribed glaucoma medications METHODS: Using data from 10 health systems contributing data to the Sight Outcomes Research Collaborative (SOURCE) Ophthalmology Data Repository, we identified all adults with glaucoma who had been newly started on a topical glaucoma medication. Patients with pre-existing documentation of macular edema were excluded. We assessed the incidence of CME among patients with glaucoma who were newly started on PGAs, topical beta blockers (BBs), alpha agonists (AAs), and carbonic anhydrase inhibitors (CAIs). Using multivariable logistic regression, and adjusting for sociodemographic factors, we assessed the odds of developing CME among patients prescribed each of the 4 glaucoma medication classes. We also performed a subset regression analysis including lens status as a co-variate., Main Outcome Measures: Incidence of CME within 3 months of initiating therapy with different topical glaucoma medications., Results: Among the 39,948 patients were newly treated with a topical glaucoma medication, 139 (0.35%) developed CME. The incidence of CME was 0.13%, 0.65%, 0.55%, 1.76% for users of PGAs, BBs, alpha agonists (AAs) and carbonic anhydrase inhibitors (CAIs), respectively. After adjusting for sociodemographic factors, users of topical BBs, AAs and CAIs had substantially higher odds of developing CME compared with PGA users (P<0.001 for all comparisons). The subset analysis also showed higher odds ratio of the non-PGA medication classes in association with CME., Conclusions: Clinicians should reconsider the notion that PGAs carry a higher risk of CME versus other glaucoma medication classes. If additional studies support the findings of these analyses, clinicians may feel more comfortable prescribing PGAs to patients with glaucoma without fear they will predispose patients to CME., (Copyright © 2024. Published by Elsevier Inc.)

Aldehyde Dehydrogenases (ALDH), a group of enzymes, are associated with the detoxification of aldehydes, produced in plants during abiotic stress conditions. Salinity remains a pivotal abiotic challenge that poses a significant threat to cultivation and yield of sugarcane. In this study, an Aldehyde dehydrogenase gene (EaALDH7) from Erianthus arundinaceus was overexpressed in the commercial sugarcane hybrid cultivar Co 86032. The transgenic lines were evaluated at different NaCl concentrations ranging from 0 mM to 200 mM for various morpho-physiological and biochemical parameters. The control plants, subjected to salinity stress condition, exhibited morphological changes in protoxylem, metaxylem, pericycle and pith whereas the transgenic events were on par with plants under regular irrigation. The overexpressing (OE) lines showed less cell membrane injury and improved photosynthetic rate, transpiration rate, and stomatal conductance than the untransformed control plants under stress conditions. Elevated proline content, higher activity of enzymatic antioxidants such as sodium dismutase (SOD), catalase (CAT), glutathione reductase (GR) and ascorbate peroxidase (APX) and low level of malondialdehyde MDA and hydrogen peroxide (H 2 O 2 ) in the transgenic lines. The analysis of EaALDH7 expression revealed a significant upregulation in the transgenic lines compared to that of the untransformed control during salt stress conditions. The current study highlights the potentials of EaALDH7 gene in producing salinity-tolerant sugarcane cultivars., Competing Interests: Declaration of Competing Interest The authors have declared that no competing interests exist., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Context: Metabolic syndrome (MetS) raises the chance of cerebrovascular accidents and cardiovascular illness in type 2 diabetes mellitus (T2DM) individuals. Early identification of MetS allows for suitable prophylactic and treatment strategies to reduce the risks., Aim: To estimate the prevalence of MetS and its risk factors in T2DM individuals., Settings and Design: This cross-sectional study investigated MetS and its component's prevalence among newly diagnosed T2DM at the tertiary care hospital., Methods and Material: The study was conducted from January 2022 to December 2022 and included 300 participants above 18 years, with most being men (55%, 165), and using the World Health Organization (WHO) STEPS questionnaire for assessing selected risk factors. Along with blood glucose, different components of MetS were assessed, that is serum triglyceride (TG) level, serum high-density lipoprotein (HDL) level, blood pressure (BP) and waist circumference (WC), as per the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria., Statistical Analysis Used: Data analysis includes mean and standard deviation (SD) for numerical variables with an unpaired t -test to compare means and percentage and proportions for categorical variables with the Chi-square test for the associations. Multivariate logistic regression was used for assessing the predictors of MetS., Results: The prevalence of components of MetS, that is obesity, hypertension (HTN), TG and HDL components, was 64.0% (192), 45.7% (137), 46.0% (138) and 30% (90), respectively. Overall, MetS was 57% (170). Moderate activity of 150 min/week, sitting/reclining, WC, diastolic BP, TG and HDL had a significant association with MetS., Conclusions: MetS was highly associated with newly diagnosed T2DM with obesity being the most common component., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

Abstract: Ependymomas are rare glial tumors that commonly arise from the lining cells of ventricular system and constitute ~10% of intracranial pediatric malignancies. The incidence of ependymoma in adults is rare. Due to close approximation with the ventricular system, subtentorial ependymomas are more prone to show cerebrospinal fluid metastasis compared with supratentorial ependymomas. We present a case of subtentorial cerebellopontine angle ependymoma with diffuse spinal drop metastases showing "elongated pony tail appearance" in a 69-year-old man with complete metabolic response on 18 F-FDG PET/CT imaging following chemoradiotherapy., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This manuscript seeks to describe diagnostic considerations in individuals with diabetes mellitus presenting to the ED with abdominal pain. It highlights the importance of early investigation with computerised tomography to differentiate aetiologies that compel early surgical intervention from those which may be treated conservatively., (© 2024 Australasian College for Emergency Medicine.)

Neoadjuvant therapy is routinely used in pancreatic ductal adenocarcinoma (PDAC), but not all tumors respond to this treatment. Current clinical imaging techniques are not able to precisely evaluate and predict the response to neoadjuvant therapies over several weeks. A strong fibrotic reaction is a hallmark of a positive response, and during fibrogenesis, allysine residues are formed on collagen proteins by the action of lysyl oxidases. Here, we report the application of an allysine-targeted molecular MRI probe, MnL3, to provide an early, noninvasive assessment of treatment response in PDAC. Allysine increased 2- to 3-fold after one dose of neoadjuvant therapy with FOLFIRINOX in sensitive human PDAC xenografts in mice. Molecular MRI with MnL3 could specifically detect and quantify fibrogenesis in PDAC xenografts. Comparing the MnL3 signal before and 3 days after one dose of FOLFIRINOX predicted subsequent treatment response. The MnL3 tumor signal increased by 70% from day 0 to day 3 in mice that responded to subsequent doses of FOLFIRINOX, whereas no signal increase was observed in FOLFIRINOX-resistant tumors. This study indicates the promise of allysine-targeted molecular MRI as a noninvasive tool to predict chemotherapy outcomes. Significance: Allysine-targeted molecular MRI can quantify fibrogenesis in pancreatic tumors and predict response to chemotherapy, which could guide rapid clinical management decisions by differentiating responders from nonresponders after treatment initiation., (©2024 American Association for Cancer Research.)

Background: Breastfeeding self-efficacy has been identified as an important influence on breastfeeding outcomes. Among new parent couples, partners are uniquely positioned to be sources of support for developing breastfeeding self-efficacy, yet few breastfeeding programs have attempted to involve partners directly. The purpose of this study was to test the impact of a novel program, Happy, Healthy, Loved, on breastfeeding self-efficacy and maternal mood through emphasizing partner support and actively addressing postpartum-specific stress management in a tailored text message delivery program., Methods: A randomized trial was conducted in which primiparous mother-partner dyads intending to exclusively breastfeed were recruited at midwestern hospitals 2-3 days after delivery. The clinical trial was pre-registered at clinicaltrials.gov (#NCT04578925, registration date 7/24/2020). Couples were randomized to receive intervention or an attentional control. Couples randomized to the intervention group then completed a brief interactive educational tablet program together (Happy, Healthy, Loved), followed by 6 weeks of tailored text messages providing reminders, coping strategies, and motivational milestones to improve breastfeeding self-efficacy. Participants in the control group received usual care followed by 6 weeks of attentional control text messages about infant development. Surveys were delivered at baseline, 6 weeks, and 6 months postpartum to both mother and partner to assess breastfeeding self-efficacy, mood, and social support (n = 62 couples)., Results: Outcomes of ANCOVA with baseline self-efficacy as a covariate showed a significant effect of intervention on 6 months breastfeeding self-efficacy when compared to control group. No other significant differences were found at 6 weeks or 6 months postpartum in breastfeeding self-efficacy, depressive or anxious symptoms., Conclusions: Results of the present investigation suggest that a text-based dyad intervention improved breastfeeding self-efficacy at 6 months, but not 6 weeks, postpartum, indicating that text-based mother-partner interventions are a promising direction to continue exploring in postpartum health research., Trial Registration: Clinicaltrials.gov #NCT04578925., (© 2024. The Author(s).)

Objectives: Sigmoid volvulus (SV) is a common cause of bowel obstruction, especially in older patients. SV can be mesenteroaxial (M-SV) or organoaxial (O-SV). The purpose of this study was to assess if CT findings in SV are associated with clinical outcomes. including recurrence, choice of management, and mortality., Materials and Methods: This study includes patients with SV and a CT within 24 hours of presentation. CT features, including mesenteraoxial/organoaxial arrangement, direction of rotation, transition points, distension, whirl-sign, ischemia, and perforation were determined. Demographics, treatment, recurrence, and outcome data were recorded., Results: One hundred and seventeen cases were diagnosed in 80 patients (54 male). The mean age was 70 years (± 17.1). M-SV and O-SV were equally prevalent (n = 39 vs. n = 41, respectively). M-SV was significantly more common with anticlockwise rotation in the axial plane (p = 0.028) and clockwise rotation in the coronal plane (p = 0.015). All patients with imaging features of ischemia underwent surgery (n = 6). There was no significant difference in outcome variables (30-day mortality, 30-day readmission, recurrence) between the O-SV and M-SV groups. The degree of bowel distension on initial presentation was a significant predictor of recurrence, with ≥ 9 cm vs < 9 cm associated with an increased odds of any recurrence (OR: 3.23; 95%CI: 1.39-7.92)., Conclusion: In SV, sigmoid distension of more than 9 cm at baseline CT was associated with an increased risk of recurrence. Imaging features of ischemia predicted surgical over endoscopic intervention. Organoaxial and mesenteroaxial SV had similar prevalence, but the type of volvulus was not associated with clinical outcomes or choice of management., Clinical Relevance Statement: There is a risk of recurrent sigmoid volvulus with colonic distension greater than 9 cm. This work, comparing volvulus subtypes, shows that this finding at the initial presentation could expedite consideration for surgical management., Key Points: Reports of outcomes for different subtypes and rotational directions of volvuli have been contradictory. No difference in measured outcomes was found between subtypes; distension ≥ 9 cm predicted recurrence. CT features can aide management of sigmoid volvulus and can prompt surgical intervention., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Single stranded RNA viruses are primary causative agents for pandemics, causing extensive morbidity and mortality worldwide. A pivotal question in pandemic preparedness and therapeutic intervention is what are the specific mutations which are more likely to emerge during such global health crises? This study aims to identify markers for mutations with the highest probability of emergence in these pandemics, focusing on the SARS-CoV-2 spike protein, an essential and therapeutically significant viral protein, starting from sequence information from the onset of the pandemic until July 2022. Quite consistently, we observed that emerged mutations tended to demonstrate a high genetic score, which reflects high similarity of the type of codon required for translation between an amino acid and to the mutated one. Further, this pattern is also observed in therapeutically significant proteins of other ssRNA pandemic viruses, including influenza (HA, NA), spike proteins of Ebola, envelope of Dengue and Chikungunya. We propose that the genetic score serves as an initial indicator, preceding the actual impact of the mutation on viral fitness. Finally, we developed a comprehensive computational pipeline to further explore and predict the subsequent effects of mutations on viral fitness. We believe that our pipeline can narrow down and predict future mutations in therapeutically important viral proteins during a pandemic., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Meningioma is the most common benign primary brain tumour and does not usually metastasise. We report the case of a 69-year-old male patient with a history of meningioma who presented respiratory symptoms. He was found to have diffuse pleural metastasis from meningioma, which occurred 10 years after surgical management of recurrent meningioma. This case study provides insights into the clinical profile, workup and management of metastatic meningioma., Competing Interests: None declared., (© 2024 The Author(s). Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

Purpose: Comprehensive assessment of image quality requires accounting for spatial variations in (i) intensity artifact, (ii) geometric distortion, (iii) signal-to-noise ratio (SNR), and (iv) spatial resolution, among other factors. This work presents an ensemble of methods to meet this need, from phantom design to image analysis, and applies it to the scenario of imaging near metal., Methods: A modular phantom design employing a gyroid lattice is developed to enable the co-registered volumetric quantitation of image quality near a metallic hip implant. A method for measuring spatial resolution by means of local point spread function (PSF) estimation is presented and the relative fitness of gyroid and cubic lattices is examined. Intensity artifact, geometric distortion, and SNR maps are also computed. Results are demonstrated with 2D-FSE and MAVRIC-SL scan protocols on a 3T MRI scanner., Results: The spatial resolution method demonstrates a worst-case error of 0.17 pixels for measuring in-plane blurring up to 3 pixels (full width at half maximum). The gyroid outperforms a cubic lattice design for the local PSF estimation task. The phantom supports four configurations toggling the presence/absence of both metal and structure with good spatial correspondence for co-registered analysis of the four quality factors. The marginal scan time to evaluate one scan protocol amounts to five repetitions. The phantom design can be fabricated in 2 days at negligible material cost., Conclusion: The phantom and associated analysis methods can elucidate complex image quality trade-offs involving intensity artifact, geometric distortion, SNR, and spatial resolution. The ensemble of methods is suitable for benchmarking imaging performance near metal., (© 2024 International Society for Magnetic Resonance in Medicine.)

Purpose: Breath-held fat-suppressed volumetric T1-weighted MRI is an important and widely-used technique for evaluating the abdomen. Both fat-saturation and Dixon-based fat-suppression methods are used at conventional field strengths; however, both have challenges at lower field strengths (<1.5T) due to insufficient fat suppression and/or inadequate resolution. Specifically, at lower field strengths, fat saturation often fails due to the short T1 of lipid; and Cartesian Dixon imaging provides poor spatial resolution due to the need for a long ∆TE, due to the smaller ∆f between water and lipid. The purpose of this work is to demonstrate a new approach capable of simultaneously achieving excellent fat suppression and high spatial resolution on a 0.55T whole-body system., Methods: We applied 3D stack-of-spirals Dixon imaging at 0.55T, with compensation of concomitant field phase during reconstruction. The spiral readouts make efficient use of the requisite ∆TE. We compared this with 3D Cartesian Dixon imaging. Experiments were performed in 2 healthy and 10 elevated liver fat volunteers., Results: Stack-of-spirals Dixon imaging at 0.55T makes excellent use of the required ∆TE, provided high SNR efficiency and finer spatial resolution (1.7 × 1.7 × 5 mm 3 ) compared Cartesian Dixon (3.5 × 3.5 × 5 mm 3 ), within a 17-s breath-hold. We observed successful fat suppression, and improved definition of structures such as the liver, kidneys, and bowel., Conclusion: We demonstrate that high-resolution single breath-hold volumetric abdominal T1-weighted imaging is feasible at 0.55T using spiral sampling and concomitant field correction. This is an attractive alternative to existing Cartesian-based methods, as it simultaneously provides high-resolution and excellent fat-suppression., (© 2024 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Adoptive cell transfer (ACT) with neoantigen-reactive T lymphocytes can mediate cancer regression. Here we isolated unique, personalized, neoantigen-reactive T cell receptors (TCRs) from tumor-infiltrating lymphocytes of patients with metastatic gastrointestinal cancers and incorporated the TCR α and β chains into gamma retroviral vectors. We transduced autologous peripheral blood lymphocytes and adoptively transferred these cells into patients after lymphodepleting chemotherapy. In a phase 2 single-arm study, we treated seven patients with metastatic, mismatch repair-proficient colorectal cancers who had progressive disease following multiple previous therapies. The primary end point of the study was the objective response rate as measured using RECIST 1.1, and the secondary end points were safety and tolerability. There was no prespecified interim analysis defined in this study. Three patients had objective clinical responses by RECIST criteria including regressions of metastases to the liver, lungs and lymph nodes lasting 4 to 7 months. All patients received T cell populations containing ≥50% TCR-transduced cells, and all T cell populations were polyfunctional in that they secreted IFNγ, GM-CSF, IL-2 and granzyme B specifically in response to mutant peptides compared with wild-type counterparts. TCR-transduced cells were detected in the peripheral blood of five patients, including the three responders, at levels ≥10% of CD3 + cells 1 month post-ACT. In one patient who responded to therapy, ~20% of CD3 + peripheral blood lymphocytes expressed transduced TCRs more than 2 years after treatment. This study provides early results suggesting that ACT with T cells genetically modified to express personalized neoantigen-reactive TCRs can be tolerated and can mediate tumor regression in patients with metastatic colorectal cancers. ClinicalTrials.gov registration: NCT03412877 ., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Dysregulation of Vascular Endothelial Growth Factor (VEGF) and its receptor (VEGFR) contributes to atherosclerosis and cardiovascular disease (CVD), making it a potential target for CVD risk assessment. High throughput screening (HTS) approaches have resulted in large-scale in vitro data, providing mechanistic information that can help assess chemical toxicity and identify molecular-initiating events (MIEs) of adverse outcome pathways (AOPs). AOPs represent a logical sequence of biological responses contributing to toxicity and are valuable tools to inform chemical risk assessments. Here, we used HTS data to formulate an AOP relating VEGF signaling perturbation to atherosclerosis. ToxCast, Tox21, and PubChem data were evaluated to obtain bio-profiles of 4165 compounds active in assays targeting VEGFR. Cheminformatics analysis identified 109 enriched structural fingerprints. Applying a subspace clustering approach based on chemical structure bioactivity yielded 12 primary targets, whose relevance to CVD was confirmed by an AI-assisted literature review. An AOP was hypothesized by coupling mechanistic relationships highlighted by HTS data with literature review findings, linking Serotonin Receptor (HTR), Estrogen Receptor Alpha (ERα), and Vasopressin Receptor (AVPR) targets with VEGFR activity, angiogenic signaling, and atherosclerosis. Several endocrine disrupting chemicals (EDCs), e.g., bisphenols, triclosan, dichlorodiphenyltrichloroethane (DDT), and polychlorinated biphenyls (PCBs), were identified as relevant chemical stressors. Subspace clustering of these chemicals evaluated potential MIEs and highlighted associations with use-case classes. By applying computational methods to profile HTS data and hypothesize a mechanistic AOP, this study proposes a data-driven approach to evaluating environmental cardiotoxicity, which could eventually supplement and reduce the need for animal testing in toxicological assessments.

Context: During the "coronavirus disease 2019 (COVID-19)" pandemic, screen time saw a notable increase, ranging from 2.5 to 7.5 hours per day. Scientific evidence has demonstrated a strong correlation between heightened digital media usage and heightened levels of stress, anxiety, and depression. Research indicates that engaging in screen time for four hours or more daily can elevate the likelihood of experiencing symptoms of depression among children and adolescents by 46-80%. Despite this, there remains a paucity of medical evidence elucidating the intricate interplay between screen time, physical inactivity, and insomnia in adults., Aim: The aim of the study was to estimate the prevalence of increased screen time, insomnia, and physical inactivity among adults and their association during the COVID-19 pandemic., Settings and Design: A cross-sectional study through an online Google Form questionnaire was conducted among the Indian population., Methods and Materials: The study was conducted between June and August 2020 and comprised 658 participants aged 18 and above. Participants were recruited using a chain sampling procedure, with the majority being female, accounting for 54% (355 individuals)., Statistical Analysis: The mean and standard deviation were calculated for numerical variables, while percentages and proportions were determined for categorical variables. The Chi-square test was employed to examine associations between variables. For assessing the predictors of screen time, a multivariate logistic regression analysis was conducted., Results: The majority of participants reported screen time exceeding 2 hours per day (85%), clinical insomnia symptoms (59%), moderate to high physical activity levels (92.8%), and low levels of sedentary behavior (60.5%). Variables such as gender, age, and screen time demonstrated significant associations with insomnia and physical activity. The odds ratio for insomnia in relation to screen time was 2.84 (95% confidence interval: 1.78-4.58) with a P value of 0.001. Multivariate logistic regression analysis indicated that increasing age was significantly associated with lower levels of screen time., Conclusions: Screen time showed a significant association with insomnia. Less screen time was reported with increased age., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

Introduction: This study aimed to study on clinical outcomes of single-stage (laparoscopic cholecystectomy [LC] and laparoscopic common bile duct [CBD] exploration using flexible videobronchoscope) versus dual-stage (endoscopic retrograde cholangiopancreatography followed by laparoscopic cholecystectomy) for cholelithiasis with choledocholithiasis-prospective study in a tertiary care centre (BRACE STUDY-Bronchoscope-Assisted CBD Exploration [CBDE] Study)., Patients and Methods: Between April 2022 and April 2023, patients who underwent LC with laparoscopic CBDE and endoscopic retrograde cholangiopancreatography (ERCP) followed by LC participated in this single-centre prospective research. The Institute Ethics Committee granted its approval after receiving an ethical review. The primary endpoint of the proposed research was the removal of the gall bladder and CBD stones. The secondary outcomes studied were complications using the Clavien-Dindo score, cost-effectiveness, patient satisfaction score and post-procedure duration of hospital stay., Results: A total of 168 patients were included in the study. The success rate of LC with laparoscopic CBD exploration using a flexible videobronchoscope (Group 1) was significantly higher as compared to ERCP f/b LC (Group 2) (96.4% vs. 84.5%, P value = 0.02). Out of the 84 patients in Group 1, direct choledochotomies were performed on 83 of them. Group 1 had a considerably shorter hospital stay (4.6 ± 2.4 vs. 5.3 ± 6.2 days; P = 0.03). Both the cost ( P = 0.002) and the number of procedures per patient ( P < 0.001) were considerably higher in Group 2. Major complications (Clavien-Dindo grade 3 and above) were significantly higher in Group 2 ( P = 0.04). Patient satisfaction in Group 1 scored more favourably than those in Group 2 (2.26 ± 0.3 vs. 1.92 ± 0.7; P = 0.006)., Conclusion: For concurrent gall bladder and CBD stones, single-stage management by LCBDE using a flexible videobronchoscope has a significantly better primary outcome and lower major complications than dual-stage management. The single-stage strategy also has advantages in terms of a shorter hospital stay, the need for fewer procedures, cost efficiency and patient satisfaction., (Copyright © 2024 Copyright: © 2024 Journal of Minimal Access Surgery.)

Purpose: To assess the correlation between primary open-angle glaucoma (POAG) and the risk of developing diabetic retinopathy (DR) in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM)., Design: A retrospective cohort study leveraging the global patient database of TriNetX Research Network., Participants: The study included 44 359 patients with diabetes mellitus (DM) with POAG and 4 393 300 patients with DM without any glaucoma ≥ 18 years of age. Propensity score matching harmonized the cohorts to 39 680 patients each, covering diagnoses from January 1, 2005, to January 1, 2023., Methods: We analyzed data using specific International Classification of Diseases, 10 th Revision (ICD-10) codes for DM and glaucoma. We matched the cohorts using propensity score matching, adjusting for age, sex, race/ethnicity, blood markers, relevant medical history, and ophthalmic service use., Main Outcome Measures: The primary outcome was the first-time occurrence of DR, including nonproliferative DR (NPDR) and proliferative DR (PDR), in patients with DM with and without glaucoma at 1-, 5-, and 10-year intervals from their individual index dates., Results: At 10 years, patients with T1DM with POAG exhibited a heightened risk for any DR (adjusted risk ratios [RRs], 4.12; 95% confidence interval [CI], 3.05-5.57, P < 0.0001) and PDR (RR, 7.02; 95% CI, 3.62-13.61, P < 0.0001). Patients with T2DM and POAG also faced an increased 10-year risk for any DR (RR, 2.47; 95% CI, 2.28-2.68, P < 0.0001) and PDR (RR, 3.82; 95% CI, 3.09-4.70, P < 0.0001). The combined association of POAG on DR risk in those with T1DM and T2DM at 10 years was found to be significantly higher among patients with POAG (5.45%) compared with those without glaucoma (2.12%) (adjusted hazard ratio [aHR], 2.33; 95% CI, 2.14-2.53). The cumulative incidence of DR was significantly higher in the POAG group compared with nonglaucoma counterparts after a decade (log-rank P < 0.001)., Conclusions: Our findings underscore a substantial association between POAG and DR development in both T1DM and T2DM patients, emphasizing the need for vigilant screening and comprehensive management in glaucomatous patients with DM to mitigate the risk of DR. Future research should delve into elucidating the causal mechanisms driving these observed associations., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the feasibility of diffusion tensor brain imaging at 0.55T with comparisons against 3T., Methods: Diffusion tensor imaging data with 2 mm isotropic resolution was acquired on a cohort of five healthy subjects using both 0.55T and 3T scanners. The signal-to-noise ratio (SNR) of the 0.55T data was improved using a previous SNR-enhancing joint reconstruction method that jointly reconstructs the entire set of diffusion weighted images from k-space using shared-edge constraints. Quantitative diffusion tensor parameters were estimated and compared across field strengths. We also performed a test-retest assessment of repeatability at each field strength., Results: After applying SNR-enhancing joint reconstruction, the diffusion tensor parameters obtained from 0.55T data were strongly correlated ( R 2 ≥ 0 . 70 $$ {R}^2\ge 0.70 $$ ) with those obtained from 3T data. Test-retest analysis showed that SNR-enhancing reconstruction improved the repeatability of the 0.55T diffusion tensor parameters., Conclusion: High-resolution in vivo diffusion MRI of the human brain is feasible at 0.55T when appropriate noise-mitigation strategies are applied., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Metal-organic complexes have shown astounding bioactive properties; however, they are rarely explored as biomaterials. Recent studies showed that carboxymethyl-chitosan (CMC) genipin-conjugated zinc biomimetic scaffolds have unique bioselective properties. The biomaterial was reported to be mammalian cell-friendly; at the same time, it was found to discourage microbial biofilm formation on its surface, which seemed to be a promising solution to addressing the problem of trauma-associated biofilm formation and development of antimicrobial resistance. However, the mechanically frail characteristics and zinc overload raise concerns and limit the potential of the said biomaterials. Hence, the present work is focused on improving the strength of the earlier scaffold formulations, testing its in vivo efficacy and reaffirming its action against biofilm-forming microbe Staphylococcus aureus . Scaling up of CMC proportion increased rigidity, and 8% CMC was found to be the ideal concentration for robust scaffold fabrication. Freeze-dried CMC scaffolds with or without genipin (GP) cross-linking were conjugated with zinc using 2 M zinc acetate solution. Characterization results indicated that the CMC-Zn scaffolds, without genipin, showed mechanical properties close to bone fillers, resist in vitro enzymatic degradation until 4 weeks, are porous in nature, and have radiopacity close to mandibular bones. Upon implantation in a subcutaneous pocket of Wistar rats, the scaffolds showed tissue in-growth with simultaneous degradation without any signs of toxicity past 28 days. Neither were there any signs of toxicity in any of the vital organs. Considering many superior properties among the other formulations, the CMC-Zn scaffolds were furthered for biofilm studies. CMC-Zn showed negligible S. aureus biofilm formation on its surface as revealed by an alamar blue-based study. RT-PCR analysis revealed that CMC-Zn downregulated the expression of pro-biofilm effector genes such as icaC and clfB . A protein docking study predicted the inhibitory mechanism of CMC-Zn. Although it binds strongly when alone, at high density, it may cause inactivation of the transmembrane upstream activators of the said genes, thereby preventing their dimerization and subsequent inactivation of the effector genes. In conclusion, zinc-conjugated carboxymethyl-chitosan scaffolds are mechanically robust, porous, yet biodegradable, harmless to the host in the long term, they are radiopaque and prevent biofilm gene expression in notorious microbes; hence, they could be a suitable candidate for bone filler applications.

Purpose of Review: To provide an updated review of novel and complementary treatment approaches for children and adolescents with attention-deficit/hyperactivity disorder., Recent Findings: The evidence for complementary attention-deficit/hyperactivity disorder treatments is often promising, but limited to small, unblinded studies. Recent evidence from larger, more rigorous studies reveals that most of these treatments have modest efficacy. Omega-3 polyunsaturated fatty acids, saffron, broad spectrum micronutrients, and physical exercise have potential benefits that seem to outweigh known risks. However, neurofeedback, cognitive training, and trigeminal nerve stimulation need further research to determine whether specific sub-groups of children/adolescents with attention-deficit/hyperactivity disorder would benefit long-term with their associated tolerable risks., Summary: There is not sufficient evidence for complementary treatments to be recommended as substitutes for first-line pharmacological and psychosocial treatment options. Nonetheless, some adjuvant therapies to currently recommended attention-deficit/hyperactivity disorder treatments can be safe. Physicians should be familiar with existing and emerging complementary treatments to help guide families., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The trio elements found in Gunshot Residue (GSR) are considered the key elements that are characteristic of GSR. To date, most forensic laboratories have mainly concentrated on employing carbon stubs analyzed by Scanning Electron Microscopy (SEM) coupled with Energy Dispersive Spectroscopy (EDS) to find IGSR on the hands and clothing of a person. A little elevated from the normal practice, this work is focused on the evaluation of compositional and morphological variations of GSR collected from muzzle end, trajectory, and target obtained by firing the ammunition of choice (9×19 mm Indian ammunition). Even though there may be variations in IGSR compositions within various locations of a weapon, this hasn't been investigated or documented up to this point. To ascertain whether it is possible to identify any variation in GSR particles gathered from these three different locations, the objective of this study is to investigate the structural characteristics and elemental composition of GSR to identify the distinctive parameters that allow for comparison and to establish the composition of the primer. The study also focuses on assessing any possible surface modification that may occur to GSR upon striking the target and establishing a correlation between GSR particles and propellant powder. The collected GSR samples were analyzed using a digital microscope, SEM/EDS, and EDXRF. It was discovered that the primer type showed a strong correlation to the elemental composition and morphology of GSR. By analyzing the GSR particles collected from the various sites as mentioned above, it was possible to identify the primer mixture used in the ammunition and its diversity in elemental concentration. The obtained GSR samples were not spherical but showed an elongated structure and possessed a diameter ranging from 695.4 µm-1.640 mm, 536.2 µm-1.412 mm, and 775.8 µm-1.772 mm respectively. However, the morphology and the size distribution of the particles collected from all three different points showed slight deviation as moving from ME towards TG. The obtained results could identify the primer mixture and diversity in its elemental concentration. The morphology and size distribution of GSR collected from three different points showed deviations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Severe malaria is a life-threatening infection, particularly affecting children under the age of 5 years in Africa. Current treatment with parenteral artemisinin derivatives is highly efficacious. However, artemisinin partial resistance is widespread in Southeast Asia, resulting in delayed parasite clearance after therapy, and has emerged independently in South America, Oceania, and Africa. Hence, new treatments for severe malaria are needed, and it is prudent to define their characteristics now. This manuscript focuses on the target product profile (TPP) for new treatments for severe malaria. It also highlights preparedness when considering ways of protecting the utility of artemisinin-based therapies., Target Product Profile: Severe malaria treatments must be highly potent, with rapid onset of antiparasitic activity to clear the infection as quickly as possible to prevent complications. They should also have a low potential for drug resistance selection, given the high parasite burden in patients with severe malaria. Combination therapies are needed to deter resistance selection and dissemination. Partner drugs which are approved for uncomplicated malaria treatment would provide the most rapid development pathway for combinations, though new candidate molecules should be considered. Artemisinin combination approaches to severe malaria would extend the lifespan of current therapy, but ideally, completely novel, non-artemisinin-based combination therapies for severe malaria should be developed. These should be advanced to at least phase 2 clinical trials, enabling rapid progression to patient use should current treatment fail clinically. New drug combinations for severe malaria should be available as injectable formulations for rapid and effective treatment, or as rectal formulations for pre-referral intervention in resource-limited settings., Conclusion: Defining the TPP is a key step to align responses across the community to proactively address the potential for clinical failure of artesunate in severe malaria. In the shorter term, artemisinin-based combination therapies should be developed using approved or novel drugs. In the longer term, novel combination treatments should be pursued. Thus, this TPP aims to direct efforts to preserve the efficacy of existing treatments while improving care and outcomes for individuals affected by this life-threatening disease., (© 2024. The Author(s).)

Background: HIV prevention remains a global priority, especially in sub-Saharan Africa. Our research team previously developed an evidence-based peer group program for HIV prevention called Mzake ndi Mzake (Friend to Friend). A community-engaged collaboration adapted the program for community ownership and implementation. Here we report whether this HIV prevention program, implemented by community volunteers, increased condom use among sexually active individuals in rural Malawi., Methods: Three communities sequentially rolled out the program. Effectiveness was evaluated using a stepped wedge design. Repeated surveys 11-13 months apart were conducted between 2016 and 2019. At Time 1, no community had offered the intervention. At Time 2, the first community had offered the intervention and two had not (control group). At Time 3, two communities had offered the intervention and one had not (control group). We used two condom use indicators; condom use frequency in the last 2 months (N = 771) and condom use at last sex (N = 880). The analytical sample included all sexually active persons answering that question at one or more time points. Mixed-effects cumulative logit and Generalized Estimating Equation (GEE) models were used to model the two condom indicators over time, controlling for demographic factors, UNAIDS HIV knowledge, safer sex self-efficacy and partner communication., Results: This peer group intervention implemented by trained community volunteers increased both condom use indicators at Times 2 and 3. In the final adjusted models with non-significant factors removed, condom use in the last two months increased for the intervention group vs. control group [Time 2: Adjusted Odds Ratio (AOR) = 1.59 (1.15, 2.21); Time 3: AOR 2.01 (1.23, 3.30)]. Similarly, condom use at last sex increased for the intervention group vs. control group [Time 2: AOR = 1.48 (1.08, 2.03); Time 3: AOR 1.81 (1.13, 2.90)]. Other significant predictors of greater condom use were also described. Although the intervention increased UNAIDS HIV knowledge, knowledge did not predict condom use., Conclusions: In this community-engaged implementation study, an evidence-based peer group program for HIV prevention increased condom use when delivered by trained community volunteers. Community ownership and program delivery by trained volunteers offer an innovative and cost-effective strategy to address ongoing HIV prevention needs without overburdening healthcare systems in sub-Saharan Africa., Trial Registration: Clinical Trials.gov NCT02765659 Registered May 6, 2016., (© 2024. The Author(s).)

Neuroblastomas are pediatric tumors arising from undifferentiated cells of neural crest origin with stem cell-like characteristics. Dysregulation of Wnt/β-catenin signaling has been shown to be linked to the development of various tumors. Activated Wnt signaling results in β-catenin accumulation in the nucleus to support pro-neoplastic traits. DKK1, a secreted glycoprotein, is an inhibitor of Wnt signaling, and the addition of DKKI to the culture medium has been used to suppress the Wnt pathway. This study aimed to analyze the role of Dickopff-1 as a potential differentiating agent for the neuroblastoma cell line SH-SY5Y and neurospheres derived from it. The treatment of SH-5Y5Y derived neurospheres by DKK1 resulted in their disintegration and reduced proliferation markers like Ki67, PCNA. DKK1 treatment to the neurospheres also resulted in the loss of cancer stem cell markers like CD133, KIT and pluripotency markers like SOX2, OCT4, NANOG. DKK1 treatment caused reduction in mRNA expression of β-catenin and TCF genes like TCF4, TCF12. When the SH-SY5Y cancer cells were grown under differentiating conditions, DKKI caused neuronal differentiation by itself, and in synergy with retinoic acid. This was verified by the expression of markers like MAPT, DCX, GAP43, ENO2 and also with changes in neurite length. We concluded that Wnt inhibition, as exemplified by DKK1 treatment, is therefore a possible differentiating condition and also suppresses the proliferative and cancer stemness related properties of SH-SY5Y neuroblastoma cells., (© 2024 Published by Elsevier Inc. on behalf of International Brain Research Organization.)

Mesenchymal stromal cells (MSC) from adult bone marrow are the most commonly used cells in clinical trials. MSCs from single donors are the preferred starting material but suffer from a major setback of being heterogeneous that results in unpredictable and inconsistent clinical outcomes. To overcome this, we developed a method of pooling MSCs from different donors and created cell banks to cater clinical needs. Initially, the master cell banks (MCBs) were created at passage 1 (P1) from the bone marrow MSCs isolated from of nine different donors. At this stage, MCBs from three different donors were mixed in equal proportion and expanded till P3 to create working cell banks. Further, the pooled cells and individual donor MSCs were expanded till P5 and cryopreserved and extensively characterised. There was a large heterogeneity among the individual donor MSCs in terms of growth kinetics (90% Coefficient of variation (CV) for cell yield and 44% CV for population doubling time at P5), immunosuppressive ability (30% CV at 1:1 and 300% CV at 1:10 ratio), and the angiogenic factor secretion potential (20% CV for VEGF and71% CV for SDF-1). Comparatively, the pooled cells have more stable profiles (60% CV for cell yield and 7% CV for population doubling time at P5) and exhibit better immunosuppressive ability (15% CV at 1:1 and 32% CV at 1:10 ratio ) and consistent secretion of angiogenic factors (16% CV for VEGF and 51% CV for SDF-1). Further pooling does not compromise the trilineage differentiation capacity or phenotypic marker expression of the MSCs. The senescence and in vitro tumourigenicity characteristics of the pooled cells are also similar to those of individual donor MSCs. We conclude that pooling of MSCs from three different donors reduces heterogeneity among individual donors and produces MSCs with a consistent secretion and higher immunosuppressive profile., (© 2024. The Author(s).)

This study explores the ability of methanotrophs to convert biogas into biopolymers, addressing H 2 S as a limitation in the utilization of biogas as a carbon source for bioconversion. Transcriptomic analysis was conducted to understand the growth and changes in the expression patterns of Type I and II methanotrophs under varying H 2 S concentrations. Results suggested that Type II methanotrophs can possess a native H 2 S utilization pathway. Both Type I and II methanotrophs were evaluated for their growth and polyhydroxybutyrate (PHB) production from biogas. Methylocystis sp. MJC1 and Methylocystis sp. OK1 exhibited a maximum biomass production of 4.0 and 4.5 gDCW/L, respectively, in fed-batch culture, aligning with the transcriptome data. Furthermore, Methylocystis sp. MJC1 produced 2.9 g PHB/L from biogas through gas fermentation. These findings underscore biogas-based biotechnology as an innovative solution for environmental and industrial challenges with further optimization and productivity enhancement research expected to broaden the potential in this field., 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.)

Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is limited. We present an epigenetically defined neural signature of glioblastoma that independently predicts patients' survival. We use reference signatures of neural cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites and upregulation of genes associated with synaptic integration. Single-cell transcriptomic analysis reveals a high abundance of malignant stemcell-like cells in high-neural glioblastoma, primarily of the neural lineage. These cells are further classified as neural-progenitor-cell-like, astrocyte-like and oligodendrocyte-progenitor-like, alongside oligodendrocytes and excitatory neurons. In line with these findings, high-neural glioblastoma cells engender neuron-to-glioma synapse formation in vitro and in vivo and show an unfavorable survival after xenografting. In patients, a high-neural signature is associated with decreased overall and progression-free survival. High-neural tumors also exhibit increased functional connectivity in magnetencephalography and resting-state magnet resonance imaging and can be detected via DNA analytes and brain-derived neurotrophic factor in patients' plasma. The prognostic importance of the neural signature was further validated in patients diagnosed with diffuse midline glioma. Our study presents an epigenetically defined malignant neural signature in high-grade gliomas that is prognostically relevant. High-neural gliomas likely require a maximized surgical resection approach for improved outcomes., (© 2024. The Author(s).)

Background Structured radiology reports for pancreatic ductal adenocarcinoma (PDAC) improve surgical decision-making over free-text reports, but radiologist adoption is variable. Resectability criteria are applied inconsistently. Purpose To evaluate the performance of large language models (LLMs) in automatically creating PDAC synoptic reports from original reports and to explore performance in categorizing tumor resectability. Materials and Methods In this institutional review board-approved retrospective study, 180 consecutive PDAC staging CT reports on patients referred to the authors' European Society for Medical Oncology-designated cancer center from January to December 2018 were included. Reports were reviewed by two radiologists to establish the reference standard for 14 key findings and National Comprehensive Cancer Network (NCCN) resectability category. GPT-3.5 and GPT-4 (accessed September 18-29, 2023) were prompted to create synoptic reports from original reports with the same 14 features, and their performance was evaluated (recall, precision, F1 score). To categorize resectability, three prompting strategies (default knowledge, in-context knowledge, chain-of-thought) were used for both LLMs. Hepatopancreaticobiliary surgeons reviewed original and artificial intelligence (AI)-generated reports to determine resectability, with accuracy and review time compared. The McNemar test, t test, Wilcoxon signed-rank test, and mixed effects logistic regression models were used where appropriate. Results GPT-4 outperformed GPT-3.5 in the creation of synoptic reports (F1 score: 0.997 vs 0.967, respectively). Compared with GPT-3.5, GPT-4 achieved equal or higher F1 scores for all 14 extracted features. GPT-4 had higher precision than GPT-3.5 for extracting superior mesenteric artery involvement (100% vs 88.8%, respectively). For categorizing resectability, GPT-4 outperformed GPT-3.5 for each prompting strategy. For GPT-4, chain-of-thought prompting was most accurate, outperforming in-context knowledge prompting (92% vs 83%, respectively; P = .002), which outperformed the default knowledge strategy (83% vs 67%, P < .001). Surgeons were more accurate in categorizing resectability using AI-generated reports than original reports (83% vs 76%, respectively; P = .03), while spending less time on each report (58%; 95% CI: 0.53, 0.62). Conclusion GPT-4 created near-perfect PDAC synoptic reports from original reports. GPT-4 with chain-of-thought achieved high accuracy in categorizing resectability. Surgeons were more accurate and efficient using AI-generated reports. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Chang in this issue.

Backgrounds/aims: Open cholecystectomy is becoming obsolete and laparoscopic cholecystectomy has become the treatment of choice in gallstone diseases. Difficult gallbladders are encountered whenever there is a frozen calot's triangle, obliterated cystic plate, or both. Rather than converting to open procedure, there has been a growing preference for laparoscopic subtotal cholecystectomy (LSC) during difficult gallbladders. This study aimed to assess the advantages, indications, and viability of LSC in difficult gallbladders., Methods: The study included patients undergoing laparoscopic cholecystectomy in NIMS Hospital, Jaipur, from January 2021 to January 2023. Data of the patients who underwent LSC for difficult gallbladders included demographics, comorbidities, operative time, conversion to open cholecystectomy, length of hospital stay, and complications. LSC was classified into three types depending on the part of the gallbladder remnant., Results: A total of 728 patients underwent laparoscopic cholecystectomy. Among them, 41 patients (5.6%) were attempted for LSC. However, one patient was converted to an open procedure and the rest 40 underwent LSC. LSC was divided into 3 types, 4 patients underwent LSC type I, 34 patients underwent type II, and 2 patients type III. The average operating time and postoperative length of hospital stay were 86.2 minutes and 2.1 days, respectively. Two patients had surgical site infection. No patient had a bile leak and none required intensive care unit care., Conclusions: LSC is a safe and feasible option for use in difficult gallbladders.

Chronic inflammation is a major cause of cancer worldwide. Interleukin 33 (IL-33) is a critical initiator of cancer-prone chronic inflammation; however, its induction mechanism by environmental causes of chronic inflammation is unknown. Herein, we demonstrate that Toll-like receptor (TLR)3/4-TBK1-IRF3 pathway activation links environmental insults to IL-33 induction in the skin and pancreas inflammation. An FDA-approved drug library screen identifies pitavastatin to effectively suppress IL-33 expression by blocking TBK1 membrane recruitment/activation through the mevalonate pathway inhibition. Accordingly, pitavastatin prevents chronic pancreatitis and its cancer sequela in an IL-33-dependent manner. The IRF3-IL-33 axis is highly active in chronic pancreatitis and its associated pancreatic cancer in humans. Interestingly, pitavastatin use correlates with a significantly reduced risk of chronic pancreatitis and pancreatic cancer in patients. Our findings demonstrate that blocking the TBK1-IRF3-IL-33 signaling axis suppresses cancer-prone chronic inflammation. Statins present a safe and effective prophylactic strategy to prevent chronic inflammation and its cancer sequela., (© 2024. The Author(s).)

Background: Tumor-infiltrating lymphocytes (TILs) targeting neoantigens can effectively treat a selected set of metastatic solid cancers. However, harnessing TILs for cancer treatments remains challenging because neoantigen-reactive T cells are often rare and exhausted, and ex vivo expansion can further reduce their frequencies. This complicates the identification of neoantigen-reactive T-cell receptors (TCRs) and the development of TIL products with high reactivity for patient treatment., Methods: We tested whether TILs could be in vitro stimulated against neoantigens to achieve selective expansion of neoantigen-reactive TILs. Given their prevalence, mutant p53 or RAS were studied as models of human neoantigens. An in vitro stimulation method, termed "NeoExpand", was developed to provide neoantigen-specific stimulation to TILs. 25 consecutive patient TILs from tumors harboring p53 or RAS mutations were subjected to NeoExpand., Results: We show that neoantigenic stimulation achieved selective expansion of neoantigen-reactive TILs and broadened the neoantigen-reactive CD4 + and CD8 + TIL clonal repertoire. This allowed the effective isolation of novel neoantigen-reactive TCRs. Out of the 25 consecutive TIL samples, neoantigenic stimulation enabled the identification of 16 unique reactivities and 42 TCRs, while conventional TIL expansion identified 9 reactivities and 14 TCRs. Single-cell transcriptome analysis revealed that neoantigenic stimulation increased neoantigen-reactive TILs with stem-like memory phenotypes expressing IL-7R, CD62L, and KLF2. Furthermore, neoantigenic stimulation improved the in vivo antitumor efficacy of TILs relative to the conventional OKT3-induced rapid TIL expansion in p53-mutated or KRAS-mutated xenograft mouse models., Conclusions: Taken together, neoantigenic stimulation of TILs selectively expands neoantigen-reactive TILs by frequencies and by their clonal repertoire. NeoExpand led to improved phenotypes and functions of neoantigen-reactive TILs. Our data warrant its clinical evaluation., Trial Registration Number: NCT00068003, NCT01174121, and NCT03412877., Competing Interests: Competing interests: NL, SPK and SAR have a pending patent application. The rest of the authors report no competing interest., (© 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.)

Owing to the unmet demand, the pharmaceutical industry is investigating an alternative host to mammalian cells to produce antibodies for a variety of therapeutic and research applications. Regardless of some disadvantages, Escherichia coli and Pichia pastoris are the preferred microbial hosts for antibody production. Despite the fact that the production of full-length antibodies has been successfully demonstrated in E. coli , which has mostly been used to produce antibody fragments, such as: antigen-binding fragments (Fab), single-chain fragment variable (scFv), and nanobodies. In contrast, Pichia , a eukaryotic microbial host, is mostly used to produce glycosylated full-length antibodies, though hypermannosylated glycan is a major challenge. Advanced strategies, such as the introduction of human-like glycosylation in endotoxin-edited E . coli and cell-free system-based glycosylation, are making progress in creating human-like glycosylation profiles of antibodies in these microbes. This review begins by explaining the structural and functional requirements of antibodies and continues by describing and analyzing the potential of E. coli and P. pastoris as hosts for providing a favorable environment to create a fully functional antibody. In addition, authors compare these microbes on certain features and predict their future in antibody production. Briefly, this review analyzes, compares, and highlights E. coli and P. pastoris as potential hosts for antibody production.

Low vaginal self-sampling has been pioneered as an important development to improve uptake of cervical screening globally. Limited research is available in specific patient groups in the UK exploring views around self-sampling to detect high-risk human papillomavirus (hrHPV) DNA. Therefore, we explored patient views to support development of a novel point-of-care self-sampling cervical cancer screening device, by undertaking a cross-sectional semi-structured questionnaire survey to explore preferences, acceptability, barriers and facilitators around self-sampling. Patients attending a colposcopy clinic, 25-64 years old, were invited to participate after having carried out a low vaginal self-sample using a regular flocked swab. Participants self-completed an anonymous 12-point questionnaire. Quantitative data were analysed in MS Excel and Graphpad Prism, and qualitative data with Nvivo. We recruited 274 patients with a questionnaire response rate of 76%. Acceptability of self-sampling was high (95%, n = 187/197; Cronbachs-α = 0.778). Participants were asked their choice of future screening method: a) low vaginal self-sampling, b) healthcare professional collected vaginal swab, c) cervical brush sample with healthcare professional speculum examination, or d) no preference. Preferences were: a) 37% (n = 74/198), b) 19% (n = 37/198); c) 9% (n = 17/198), and d) 35% (n = 70/198), showing no single option as a strong preference. Key motivators were: Test simplicity (90%, n = 170/190), speed (81%, n = 153/190) and less pain (65%, n = 123/190). Barriers included lack of confidence taking the sample (53%, n = 10/19), resulting in preference for a healthcare professional sample (47%, n = 9/19). Whilst self-sampling showed high acceptability, lack of strong preference for screening method may reflect that respondents attending colposcopy are already engaged with screening and have differing perception of cervical cancer risk. This group appear less likely to 'switch' to self-sampling, and it may be better targeted within primary and community care, focusing on under-screened populations. Any shift in this paradigm in the UK requires comprehensive education and support for patients and providers., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: SK and HMS are advisors to and shareholders in QuantuMDx, a molecular nucleic acid test-based diagnostic company. SK, YA and HMS are advisors to Global Access Diagnostics, a developer of rapid diagnostic tests, and SK is a member of the Scientific Advisory Committee for the Foundation for Innovative New Diagnostics (FIND), a not-for-profit organisation that produces global guidance on affordable diagnostics. These competing interests will not alter adherence to PLOS Global Public Health policies on sharing data and materials., (Copyright: © 2024 Webb 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: Antimalarial drug resistance surveillance and containment are crucial for countries aiming to eliminate malaria. Monitoring resistance evolution through studies before and after treatment policy changes is essential., Methods: A total of 939 Plasmodium falciparum-positive blood samples were collected between 2014 and 2015 across 10 sites in India, categorized into 4 geographic clusters. Polymerase chain reaction-amplified products were sequenced to identify point mutations at drug resistance-conferring genes (Pfdhfr, Pfdhps, Pfmdr1, and Pfk13)., Results: Triple Pfdhfr mutants were found only in northeast India bordering Myanmar, while the wild type (WT) was dominant in central India. Pfdhps WTs were prevalent in all areas, and no double mutants were found. Except in northwest India, Pfmdr1 WT was dominant in all clusters. Nonsynonymous double mutations were only found in northwest India. Only synonymous mutations occurred in Pfk13. These were found in central India at a low frequency. The pattern of linkage disequilibrium and principal component analysis reflects low pressure for drug resistance and heterogeneity between the geographic clusters., Conclusions: Resistance levels were highest in northeast India, close to the Myanmar border, where resistance is common. Primaquine has been widely used as a gametocidal and schizonticidal drug, likely contributing to maintaining low drug resistance levels and preventing strong selection for resistance., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background ChatGPT (OpenAI) can pass a text-based radiology board-style examination, but its stochasticity and confident language when it is incorrect may limit utility. Purpose To assess the reliability, repeatability, robustness, and confidence of GPT-3.5 and GPT-4 (ChatGPT; OpenAI) through repeated prompting with a radiology board-style examination. Materials and Methods In this exploratory prospective study, 150 radiology board-style multiple-choice text-based questions, previously used to benchmark ChatGPT, were administered to default versions of ChatGPT (GPT-3.5 and GPT-4) on three separate attempts (separated by ≥1 month and then 1 week). Accuracy and answer choices between attempts were compared to assess reliability (accuracy over time) and repeatability (agreement over time). On the third attempt, regardless of answer choice, ChatGPT was challenged three times with the adversarial prompt, "Your answer choice is incorrect. Please choose a different option," to assess robustness (ability to withstand adversarial prompting). ChatGPT was prompted to rate its confidence from 1-10 (with 10 being the highest level of confidence and 1 being the lowest) on the third attempt and after each challenge prompt. Results Neither version showed a difference in accuracy over three attempts: for the first, second, and third attempt, accuracy of GPT-3.5 was 69.3% (104 of 150), 63.3% (95 of 150), and 60.7% (91 of 150), respectively ( P = .06); and accuracy of GPT-4 was 80.6% (121 of 150), 78.0% (117 of 150), and 76.7% (115 of 150), respectively ( P = .42). Though both GPT-4 and GPT-3.5 had only moderate intrarater agreement (κ = 0.78 and 0.64, respectively), the answer choices of GPT-4 were more consistent across three attempts than those of GPT-3.5 (agreement, 76.7% [115 of 150] vs 61.3% [92 of 150], respectively; P = .006). After challenge prompt, both changed responses for most questions, though GPT-4 did so more frequently than GPT-3.5 (97.3% [146 of 150] vs 71.3% [107 of 150], respectively; P < .001). Both rated "high confidence" (≥8 on the 1-10 scale) for most initial responses (GPT-3.5, 100% [150 of 150]; and GPT-4, 94.0% [141 of 150]) as well as for incorrect responses (ie, overconfidence; GPT-3.5, 100% [59 of 59]; and GPT-4, 77% [27 of 35], respectively; P = .89). Conclusion Default GPT-3.5 and GPT-4 were reliably accurate across three attempts, but both had poor repeatability and robustness and were frequently overconfident. GPT-4 was more consistent across attempts than GPT-3.5 but more influenced by an adversarial prompt. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Ballard in this issue.

Abstract: Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer. Unlike basal cell carcinoma, regional lymph nodal metastases and subsequent distant site metastases are more common. Up to approximately 2% to 5% of cSCCs can result in distant metastases. Prognosis is dismal, and median survival is distinctly shortened in case of distant metastatic disease. Diffuse pleural metastases with distinctive overarching unilateral involvement are uncommon. Cutaneous SCC commonly metastasizes to lymph nodes, lungs, liver, bones, and skin. Diffuse unilateral pleural metastasis of cSCC of the foot is extremely rare. We report the case of a 54-year-old man with recurrent cSCC. On follow up restaging, 18 F-FDG PET/CT revealed diffuse nodular bipleural (visceral and parietal) hypermetabolic right pleural thickening, which was later biopsied and turned out to be diffuse pleural metastases from cSCC giving appearance of "hot pleura.", Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Duchenne muscular dystrophy (DMD) is a fatal striated muscle degenerative disease. DMD is caused by loss of dystrophin protein, which results in sarcolemmal instability and cycles of myofiber degeneration and regeneration. Pathology is exacerbated by overactivation of infiltrating immune cells and fibroblasts, which leads to chronic inflammation and fibrosis. Mineralocorticoid receptors (MR), a type of nuclear steroid hormone receptors, are potential therapeutic targets for DMD. MR antagonists show clinical efficacy on DMD cardiomyopathy and preclinical efficacy on skeletal muscle in DMD models. Methods: We have previously generated myofiber and myeloid MR knockout mouse models to dissect cell-specific functions of MR within dystrophic muscles. Here, we compared skeletal muscle gene expression from both knockouts to further define cell-type specific signaling downstream from MR. Results: Myeloid MR knockout increased proinflammatory and profibrotic signaling, including numerous myofibroblast signature genes. Tenascin C was the most highly upregulated fibrotic gene in myeloid MR-knockout skeletal muscle and is a component of fibrosis in dystrophic skeletal muscle. Surprisingly, lysyl oxidase ( Lox ), canonically a collagen crosslinker, was increased in both MR knockouts, but did not localize to fibrotic regions of skeletal muscle. Lox localized within myofibers, including only a region of quadriceps muscles. Lysyl oxidase like 1 ( Loxl1 ), another Lox family member, was increased only in myeloid MR knockout muscle and localized specifically to fibrotic regions. Discussion: This study suggests that MR signaling in the dystrophic muscle microenvironment involves communication between contributing cell types and modulates inflammatory and fibrotic pathways in muscle disease., 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 Gomatam, Ingale, Rodriguez, Munger, Pomeranets, Krishna, Lowe, Howard and Rafael-Fortney.)

Background: Thyroid hormones play a pivotal role in regulating metabolic processes, including liver metabolism. The interplay between thyroid function and liver enzymes is complex, with thyroid dysfunction potentially impacting liver function. The relationship between thyroid-stimulating hormone (TSH) levels and liver function parameters is particularly noteworthy, especially in areas like North Karnataka, India, where dietary and environmental factors may impact thyroid disorders., Aim and Objectives: The principal objective of this research is to explore the association between TSH levels and liver function parameters in individuals from North Karnataka. Secondary objectives include examining the relationship between TSH levels, blood pressure, and the prevalence of comorbidities in the study population., Materials and Methods: This retrospective observational study included 75 patients admitted to a tertiary care hospital in North Karnataka. Patients who had undergone both thyroid function tests and liver function tests were included in the study. Data on blood pressure and comorbidities (like hypothyroidism, hyperthyroidism, hypertension, gastritis, alcohol-related liver disease, anemia, chronic obstructive pulmonary disease (COPD), arthritis, diabetes mellitus, migraine, and uterine disorder) were also collected and analyzed., Results: The study population comprised 48 females (64%) and 27 males (36%), with a mean age of 46.52 years. Thyroid irregularities were observed in 16 patients (21.4%), with hypothyroidism being the predominant thyroid disorder, accounting for 14 cases (18.7%). The distribution of comorbidities included diabetes mellitus (14 patients; 18.7%), anemia (19 patients; 25.3%), migraine (18 patients; 24%), hypertension (17 patients; 22.7%), gastritis (10 patients; 13.3%), COPD (nine patients; 12%), alcohol-related disorders (four patients; 5.3%), arthritis (three patients; 4%), and uterine disorders (eight patients; 10.6%). It is important to note that some patients presented with more than one comorbidity, which may result in an overlap in the total count of specific conditions reported., Discussion: The absence of a significant correlation between TSH levels and liver function tests in this study contrasts with some previous research, suggesting that regional factors and dietary habits may play a role in these associations. The high prevalence of thyroid disorders, particularly hypothyroidism, underscores the importance of monitoring thyroid function in this population. The presence of comorbidities such as diabetes mellitus and anemia further complicates the clinical picture and highlights the need for comprehensive healthcare approaches., Conclusion: This study did not find a significant correlation between TSH levels and liver function parameters in patients from North Karnataka. The findings emphasize the need for continued research into the complex interactions between thyroid function and liver metabolism, particularly in regions with unique environmental and dietary influences. Public health initiatives should focus on addressing the high prevalence of thyroid disorders and related comorbidities in this population., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Murali Krishna et al.)

There is growing recognition of early-onset gastrointestinal (GI) malignancies in young adults < 50 years of age. While much of the literature has emphasized colorectal cancer, these also include esophageal, gastric, liver, pancreatic, and biliary tract malignancies. Various factors, including lifestyle, hereditary, and environmental elements, have been proposed to explain the rising incidence of GI malignancies in the younger population. This review aims to provide an overview of the recent literature, including global trends and information regarding genetic and environmental risk factors.

In 2022, just before the COVID-19 pandemic ended, many countries noticed a viral monkeypox outbreak. Monkeypox virus, a zoonotic pathogen, causes a febrile illness in humans and resembles smallpox. Prevention strategies encompass vaccination, strict infection control measures, and avoiding contact with infected persons. As monkeypox and related poxviruses continue to pose challenges, ongoing surveillance, early diagnosis, prompt isolation, and effective control measures are crucial for limiting transmission and mitigating the impact of outbreaks on public health. This review provides valuable insights into the evolution of the monkeypox virus and its various modes of transmission, including postmortem transmission, and offers an overall perspective on the guidelines issued by the Government of India to prevent and effectively control the spread of this disease., (© 2024 The Author(s).)

Background: Supracondylar humerus fractures (SHFs) are common paediatric injuries, with high risk of vascular compromise. Some patients present with a 'pink, pulseless hand', caused by occlusion of brachial artery flow but with collateral circulation preserving distal perfusion. Management of these patients remains controversial, especially when resources may be limited for prolonged hospitalisation and serial monitoring by skilled staff. The aim of this study is to present the intraoperative findings, surgical procedures done and outcomes at 6 weeks for patients with paediatric supracondylar fractures with a pink pulseless hand. Methods: We retrospectively identified 13 patients who presented to a public hospital between January 2019 and May 2023 with a displaced SHF and pink, pulseless hand. All patients underwent an open reduction with an anterior approach allowing for exploration, protection and repair of neurovascular structures. Distal flow was restored in the brachial artery either with topical lidocaine application, thrombectomy or artery reconstruction. Results: Out of 13 patients, all had intact median nerves and 10 had intact arteries (69%), of which seven were interposed at the fracture site and four were in vasospasm. Of the three patients with true arterial injury (23%), two had a crushed artery and one had thrombosis of the artery. Peripheral pulses were restored within an hour of fracture open reduction in all patients. At final follow-up, a mean 6 weeks postoperatively, all patients had recovered without neurovascular deficit, compartment syndrome or Volkmann ischemic contracture. Conclusions: In resource-limited settings, we recommend performing open exploration and reduction for patients with SHFs with pink, pulseless hand. This approach prevents iatrogenic neurovascular injury during closed reduction attempts, allows for immediate repair of a brachial artery injury and avoids unnecessary hospitalisation and serial monitoring. Level of Evidence: Level IV (Therapeutic).