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Abstract Background Conventional therapies in cancer treatment face challenges including drug resistance, lack of specificity, and severe adverse reactions. This study explores the potential of liposomal transdermal delivery systems as an alternative to current therapies with improved BA and PK. The objective of the study was to formulate gefitinib liposomes by thin film hydration technique (TFH) using lipoid S100. A central composite design (CCD) was used to develop and optimize GEF-LIP-TDDs and to analyze the optimum concentrations of the selected variables (phospholipid, cholesterol) in liposomal formation. The model fitting was performed using Design-Expert (Stat-Ease, Ver 13). The GEF liposomes were evaluated for %EE, mean particle size and PDI. The optimized liposomes were fabricated as a transdermal patch by mercury substrate method and evaluated for %drug content, in vitro diffusion, in vivo biodistribution (PK and BA), and skin irritation studies in female Albino Wistar rats. The stability of the optimized transdermal patch was also assessed for 3 months. Results The CCD model was significant with F-value of 37.97, P-value of 0.0500 and R 2 of 0.9644. The average vesicle size, PDI, and ZP of GEF-LIPs (F1–F13) were found to be between 112.8 to 373.7 nm, 0.186 to 0.510 and − 3.69 to − 82.2 mV, respectively. F3-GEF-LIP exhibited a mean vesicle size of 96.07 nm, ZP of − 46.06 mV, and a PDI of 0.423. F3-GEF-LIP demonstrated exceptional %EE (97.79) and sustained release effect (%CDR, 83.32) following a diffusion-controlled mechanism. TEM images confirmed liposomes of multivesicular type (MVV,

Vision-language models (VLMs) have shown remarkable potential in various domains, particularly in zero-shot learning applications. This research focuses on evaluating the performance of notable VLMs—CLIP, PLIP, and BiomedCLIP—in the classification of blood cells, with a specific emphasis on distinguishing between normal and malignant (cancerous) cells datasets. While CLIP demonstrates robust zero-shot capabilities in general tasks, this study probes its biomedical adaptations, PLIP and BiomedCLIP, to assess their effectiveness in specialized medical tasks, such as hematological image classification. Additionally, we investigate the impact of prompt engineering on model performance, exploring how variations in prompt construction influence accuracy across these biomedical datasets. Extensive experiments were conducted on a variety of biomedical images, including microscopic blood cell images, brain MRIs, and chest X-rays, providing a comprehensive evaluation of the VLMs' applicability in medical imaging. Our findings reveal that while CLIP, trained on general datasets, performs well in broader contexts, PLIP and BiomedCLIP—optimized for medical imagery—demonstrate enhanced accuracy in medical settings, particularly in hematology. The results underscore the strengths and limitations of these models, offering valuable insights into their adaptability, precision, and potential for future applications in medical image classification.

Abstract Inactivating mutations in SMARCB1 confer an oncogenic dependency on EZH2 in atypical teratoid rhabdoid tumors (ATRTs), but the underlying mechanism has not been fully elucidated. We found that the sensitivity of ATRTs to EZH2 inhibition (EZH2i) is associated with the viral mimicry response. Unlike other epigenetic therapies targeting transcriptional repressors, EZH2i-induced viral mimicry is not triggered by cryptic transcription of endogenous retroelements, but rather mediated by increased expression of genes enriched for intronic inverted-repeat Alu (IR-Alu) elements. Interestingly, interferon-stimulated genes (ISGs) are highly enriched for dsRNA-forming intronic IR-Alu elements, suggesting a feedforward loop whereby these activated ISGs may reinforce dsRNA formation and viral mimicry. EZH2i also upregulates the expression of full-length LINE-1s, leading to genomic instability and cGAS/STING signaling in a process dependent on reverse transcriptase activity. Co-depletion of dsRNA sensing and cytoplasmic DNA sensing completely rescues the viral mimicry response to EZH2i in SMARCB1-deficient tumors.

Abstract After disasters, many people seek compensation for physical, psychological or economic damages. However, compensation processes can be perceived as arduous and unfair and potentially create stress for both individuals and communities. This systematic review explored the psychosocial impacts of post-disaster compensation processes, including compensation sought through both litigation and government assistance programmes. We searched seven databases, hand-searched reference lists of included studies, and used thematic analysis to synthesise results of included studies. We screened 6,532 papers, ultimately including 66 in the review. While we found mixed evidence regarding the relationship between individual mental health and the compensation process, many studies suggested the process placed demands on emotional resources and could cause stress. Numerous challenges of the compensation process were described, including complicated paperwork, lengthy processes, inadequate information, confusing eligibility criteria, lack of inter-agency cooperation, poor understanding of communities’ unique needs, insufficient pay-outs, and politicisation of the process. Inequities in compensation distribution introduced additional stress to already traumatised communities, who often experienced resentment, envy and conflict. The mixed nature of the relationship between mental health and the compensation process was evident in research trends where a small number of studies reported positive findings related to relating to gratitude, helpfulness of compensation and strengthened community relationships, while a substantial number of others reported negative impacts including higher mental health problems. Positive and negative impacts were reported for both litigation and non-litigation compensation-seeking. The nuanced dynamics of these findings are described in greater detail within the paper. It is important that compensation regulators consider the potential impacts on individuals and communities and take steps to address compensation inequities. This enhanced understanding of how those affected by disasters can rebuild their lives and furthering understanding of how to support them will enable evidence-based approaches to building resilience and planning for long-term recovery. Significant compensation process improvements could be realised by ensuring clear communication and transparent decision-making. Overall, this review underscores the importance of ensuring that compensation processes are fair and straightforward so they can repair material losses without deteriorating the social norms and relationships of affected communities.

Abstract Aims Heart failure (HF) is a clinical syndrome with no definitive diagnostic tests. HF registries are often based on manual reviews of medical records of hospitalized HF patients identified using International Classification of Diseases (ICD) codes. However, most HF patients are not hospitalized, and manual review of big electronic health record (EHR) data is not practical. The US Department of Veterans Affairs (VA) has the largest integrated healthcare system in the nation, and an estimated 1.5 million patients have ICD codes for HF (HF ICD‐code universe) in their VA EHR. The objective of our study was to develop artificial intelligence (AI) models to phenotype HF in these patients. Methods and results The model development cohort (n = 20 000: training, 16 000; validation 2000; testing, 2000) included 10 000 patients with HF and 10 000 without HF who were matched by age, sex, race, inpatient/outpatient status, hospital, and encounter date (within 60 days). HF status was ascertained by manual chart reviews in VA's External Peer Review Program for HF (EPRP‐HF) and non‐HF status was ascertained by the absence of ICD codes for HF in VA EHR. Two clinicians annotated 1000 random snippets with HF‐related keywords and labelled 436 as HF, which was then used to train and test a natural language processing (NLP) model to classify HF (positive predictive value or PPV, 0.81; sensitivity, 0.77). A machine learning (ML) model using linear support vector machine architecture was trained and tested to classify HF using EPRP‐HF as cases (PPV, 0.86; sensitivity, 0.86). From the ‘HF ICD‐code universe’, we randomly selected 200 patients (gold standard cohort) and two clinicians manually adjudicated HF (gold standard HF) in 145 of those patients by chart reviews. We calculated NLP, ML, and NLP + ML scores and used weighted F scores to derive their optimal threshold values for HF classification, which resulted in PPVs of 0.83, 0.77, and 0.85 and sensitivities of 0.86, 0.88, and 0.83, respectively. HF patients classified by the NLP + ML model were characteristically and prognostically similar to those with gold standard HF. All three models performed better than ICD code approaches: one principal hospital discharge diagnosis code for HF (PPV, 0.97; sensitivity, 0.21) or two primary outpatient encounter diagnosis codes for HF (PPV, 0.88; sensitivity, 0.54). Conclusions These findings suggest that NLP and ML models are efficient AI tools to phenotype HF in big EHR data to create contemporary HF registries for clinical studies of effectiveness, quality improvement, and hypothesis generation.

Antimicrobial resistance (AMR), is a chief worldwide public health concern with grave health and socio-economic repercussions. Besides improper use of antibiotics, exposure to contaminated water or soil, and close contact with infected individuals; consumption of food products derived from animals carrying antimicrobial-resistant bacteria and genes is a major pathway for transferring AMR to humans. The occurrence of antimicrobial resistance in bacteria can result from both innate and acquired mechanisms, and its spread among bacteria is contributed by the environment, animals, and humans. Analysis of available data shows that non-therapeutic antimicrobial administration to animals increases resistance rates in bacteria in their gut and surroundings. The food supply chain facilitates the transfer of genes associated with AMR and despite considerable efforts to restrict antibiotic overuse, numerous regions of the world are witnessing a surge in clinical antibiotic resistance rates. To address this multifaceted resistance issue effectively, a "One Health" approach is critical, along with concerted efforts across all sectors. Considering the importance and scientific concern of this emerging public health issue, a thorough review of the available literature on the transmission of AMR from animal-derived foods to humans is presented in this paper.

Background: The combination of oral pentoxifylline (Ptx) and vitamin E (VitE) has been used to treat radiation-induced fibrosis and soft tissue injury. Here, we review outcomes and perform a radiomic analysis of treatment effects in patients prescribed Ptx + VitE at our institution for the treatment of radiation necrosis (RN). Methods: A total of 48 patients treated with stereotactic radiosurgery (SRS) had evidence of RN and had MRI before and after starting Ptx + VitE. The radiation oncologist’s impression of the imaging in the electronic medical record was used to score response to treatment. Support Vector Machine (SVM) was used to train a model of radiomics features derived from radiation necrosis on pre- and 1st post-treatment T1 post-contrast MRIs that can classify the ultimate response to treatment with Ptx + VitE. Results: A total of 43.8% of patients showed evidence of improvement, 18.8% showed no change, and 25% showed worsening RN upon imaging after starting Ptx + VitE. The median time-to-response assessment was 3.17 months. Nine patients progressed significantly and required Bevacizumab, hyperbaric oxygen therapy, or surgery. Patients who had multiple lesions treated with SRS were less likely to show improvement (p = 0.037). A total of 34 patients were also prescribed dexamethasone, either before (7), with (16), or after starting (11) treatment. The use of dexamethasone was not associated with an improved response to Ptx + VitE (p = 0.471). Three patients stopped treatment due to side effects. Finally, we were able to develop a machine learning (SVM) model of radiomic features derived from pre- and 1st post-treatment MRIs that was able to predict the ultimate treatment response to Ptx + VitE with receiver operating characteristic (ROC) area under curve (AUC) of 0.69. Conclusions: Ptx + VitE appears safe for the treatment of RN, but randomized data are needed to assess efficacy and validate radiomic models, which may assist with prognostication.

Abstract Background Cardiac ochronosis, presenting as a rare manifestation of alkaptonuria, an autosomal recessive disorder, is characterised by black pigmentation of calcified cardiac valves and atherosclerotic plaques. We report an intraoperative dilemma on the discovery on the black aortic valve in a case of an old lady with degenerative calcific aortic stenosis. Case presentation A 60-year-old lady was electively admitted for valve replacement with a bioprosthetic valve for severe aortic stenosis. She was symptomatic with complaints of headache and giddiness and had a pressure gradient of 113/17mmhg across the aortic valve. Intraoperatively, she was found to have cardiac ochronosis on the discovery of pigmented aortic intima extending to the valve leaflets and underwent valve replacement with a mechanical prosthetic valve. She was post-operatively evaluated for the same and diagnosed with alkaptonuria. Though the surgery went uneventful and the patient was discharged without any complication, she was advised to be on regular follow-up to assess valve gradients, paravalvular leaks and to monitor the disease progression. Conclusion The presented case sheds light on the rare cardiac manifestation of alkaptonuria. In the absence of definitive pre-operative diagnosis, intraoperative findings played a pivotal role in guiding the surgical approach and choice of prosthetic valve. The decision to use a mechanical valve was influenced by the potential risks associated with bioprosthetic valves in the setting of ochronosis. Ongoing follow-up and monitoring are essential to assess the durability of the chosen prosthetic valve and to manage any long-term consequences of the underlying metabolic condition.

Abstract In the present era, the energy sector is undergoing an intense transformation, which encourages numerous research efforts aimed at reducing and reusing energy waste. One of the main areas of focus is thermoelectric energy, where telluride compounds have attracted researchers due to their remarkable ability to convert thermal energy into electrical energy. We focused this study on finding out how well strontium telluride (SrTe) can be used to generate thermoelectric power by testing it under up to 10% compression strain. We have used advanced computational approaches to increase the accuracy of our results, specifically the HSE hybrid functional with the Wannier interpolation method. This method is primarily employed to analyze electronic properties; however, our research extends its utility to investigate thermoelectric characteristics. Our findings provide accurate predictions for both electronic and thermoelectric properties. The above method has successfully achieved a significant improvement of 58% in the electronic band gap value, resulting in a value of 2.83 eV, which closely matches the experimental results. Furthermore, the Figure of Merit 0.95 is obtained, which is close to the ideal range. Both the band gap value and the thermoelectric figure of merit decrease when the compression strain is increased. These findings emphasize the importance of using SrTe under specific conditions. The findings of this work provide motivation for future researchers to investigate the environmental changes in the thermoelectric potential of SrTe.

Abstract Growth in the green jobs sector has increased demand for college graduates who are prepared to enter the workforce with interdisciplinary sustainability skills. Simultaneously, scholarly calls for interdisciplinary collaboration in the service of addressing the societal challenges of enhancing resilience and sustainability have also increased in recent years. However, developing, executing, and assessing interdisciplinary content and skills at the post-secondary level has been challenging. The objective of this paper is to offer the Food-Energy-Water (FEW) Nexus as a powerful way to achieve sustainability competencies and matriculate graduates who will be equipped to facilitate the transformation of the global society by meeting the targets set by the United Nations Sustainable Development Goals. The paper presents 10 curricular design examples that span multiple levels, including modules, courses, and programs. These modules enable clear evaluation and assessment of key sustainability competencies, helping to prepare graduates with well-defined skillsets who are equipped to address current and future workforce needs.

Lung cancer is the leading cause of cancer-related deaths worldwide. Many patients tend to have a very poor prognosis due to being diagnosed at an advanced stage especially in densely populated nations. The current study presents a case series of lung tumors. All the lung tumors presented as endobronchial mass; however histopathological diagnoses were different in each of the lung tumors after bronchoscopic guided lung mass biopsies. The first case was small cell lung cancer (SCLC) with endobronchial growth in a 64‑year‑old male. Bronchoscopy was suggestive of Left vocal cord palsy. The tiny nodule was seen over both cords with nodule present over carina. Chest CT scans revealed a well-defined irregularly shaped mass lesion with spiculated margin seen in the left lower lobe. The analysis of a biopsy specimen obtained from the tumor resulted in a diagnosis of SCLC. The second case was of non-small cell lung cancer (NSCLC) with endobronchial growth in a 77-year-old male. CECT reveals a right upper lobe malignant mass lesion with mediastinal invasion with mediastinal metastatic nodes. Bronchoscopy revealed a right upper lobe malignant mass. Histopathological examination revealed features consistent with NSCLC of Squamous cell carcinoma. The third case was a 58-year-old male whose CECT Thorax revealed a malignant pulmonary mass lesion in the left hilar region. Bronchoscopy was suggestive of endobronchial growth present in Left main bronchus around 1.5 cm from the carina. Tissue taken from the Left Hilar mass showed features of NSCLC-Adenocarcinoma carcinoma of the lung.

Abstract Background Heart failure (HF) with preserved or mildly reduced ejection fraction includes a heterogenous group of patients. Reclassification into distinct phenogroups to enable targeted interventions is a priority. This study aimed to identify distinct phenogroups, and compare phenogroup characteristics and outcomes, from electronic health record data. Methods 2,187 patients admitted to five UK hospitals with a diagnosis of HF and a left ventricular ejection fraction ≥ 40% were identified from the NIHR Health Informatics Collaborative database. Partition-based, model-based, and density-based machine learning clustering techniques were applied. Cox Proportional Hazards and Fine-Gray competing risks models were used to compare outcomes (all-cause mortality and hospitalisation for HF) across phenogroups. Results Three phenogroups were identified: (1) Younger, predominantly female patients with high prevalence of cardiometabolic and coronary disease; (2) More frail patients, with higher rates of lung disease and atrial fibrillation; (3) Patients characterised by systemic inflammation and high rates of diabetes and renal dysfunction. Survival profiles were distinct, with an increasing risk of all-cause mortality from phenogroups 1 to 3 (p

Abstract Background Cardiac troponin is commonly raised in patients presenting with malignancy. The prognostic significance of raised troponin in these patients is unclear. Objectives We sought to investigate the relation between troponin and mortality in a large, well characterised cohort of patients with a routinely measured troponin and a primary diagnosis of malignancy. Methods We used the National Institute for Health Research (NIHR) Health Informatics Collaborative data of 5571 patients, who had troponin levels measured at 5 UK cardiac centres between 2010 and 2017 and had a primary diagnosis of malignancy. Patients were classified into solid tumour or haematological malignancy subgroups. Peak troponin levels were standardised as a multiple of each laboratory’s 99th -percentile upper limit of normal (xULN). Results 4649 patients were diagnosed with solid tumours and 922 patients with haematological malignancies. Raised troponin was an independent predictor of mortality in all patients (Troponin > 10 vs.

Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline. While these goals are primarily achieved using biological or chemical strategies, harnessing cell mechanosensitivity represents a promising – albeit less studied – physical pathway to promote bioprocessing endpoints, yet identifying which mechanical parameters influence cell activities has remained elusive. We tested the hypothesis that mechanical signals, delivered non-invasively using low-intensity vibration (LIV; 90%), and LIV effectively scaled up to T75 flasks. Ultimately, when LIV is tailored to the target cell population, it's highly efficient transmission across media represents a means to non-invasively augment biomanufacturing endpoints for both adherent and suspended cells, and holds immediate applications, ranging from small-scale, patient-specific personalized medicine to large-scale commercial bio-centric production challenges.

Objectives: Knowledge, access, and use of testing and antiviral treatments is critical to managing and mitigating the continuing burden of the novel Corona Virus (COVID-19) in the United States. This study measured knowledge, attitude, behaviors, and self-reported barriers towards COVID-19 testing and outpatient anti-viral medications (OPA) treatments among Black and older individuals who face greater hospitalization and mortality from the disease. Study design: Cross-sectional structured survey. Methods: Respondents were randomly selected from an opt-in national panel in December 2022. Equal numbers of Black and White US adults over the age of 40 (n = 1037) completed the 42 item online survey. The main measures were key sociodemographic variables of respondents, race, age, political affiliation and COVID-19 attitudes, beliefs, testing behaviors, and knowledge and barriers to OPA access. Results: Overall, awareness and knowledge of COVID-19 outpatient treatments was low. Black respondents were more likely to test for COVID-19 than White respondents but less likely to know about OPA treatments. Insurance coverage was a significant factor in use of home tests. Knowledge of OPA treatments was low across groups. White respondents were more likely than Black respondents to be aware of OPA treatments (1.75, 95 % CI [1.31–2.33]) as were higher income respondents (1.13, 95 % CI [1.08–1.17]) and self-identified Liberals (1.79, 95 % CI [1.29–2.49]). Conclusions: Clinicians should know large numbers of patients may not be testing for COVID-19, nor are they aware of outpatient treatment options and may hold inaccurate beliefs about them. Developing culturally specific patient education materials are warranted to increase testing, utilization of vaccinations and OPAs.

Background:. The plastic and reconstructive surgery (PRS) match has become more competitive with an emphasis on research productivity. With the transition of the US Medical Licensing Examination step 1 examination to pass-fail grading, alternative evaluation metrics for residency applications are needed. Our study provides a landscape of the incidence of research years amongst integrated PRS residents and the potential impacts of gender and race. Methods:. A retrospective study was conducted for all integrated PRS residents who matched between 2017 and 2022, using publicly available sources including residency websites, PubMed, Doximity, and social media. Demographics, educational background, and participation in a dedicated PRS research year were recorded. Results:. Among 993 residents across 85 accredited integrated PRS programs, 15.7% (156 of 993) took a research year, with a significant increase over 6 years (R2 = 0.73, P = 0.019). The majority were men at 51.9%, and White at 53.5%, with underrepresented in medicine residents comprising 13.5%. A total of 73.1% came from a medical school with a home program, and 52.6% matched into a top 20 residency program. No significant difference was seen in the racial/ethnic or gender representation of residents who took a research year compared with all PRS applicants and active PRS residents. Conclusions:. Research years before applying to residency are becoming more common among integrated PRS residents. Research years are especially common with students who do not have a home program and may help them gain skills and access to mentorship that improves the likelihood of matching.

Background Reduced estimated glomerular filtration rate (eGFR) is associated with lower use of invasive management and increased mortality after acute coronary syndrome (ACS). The reasons for this are unclear.Methods A retrospective clinical cohort study was performed using data from the English National Institute for Health Research Health Informatics Collaborative (2010–2017). Multivariable logistic regression was used to investigate whether eGFR

Abstract Mitochondrial transcription factor A (TFAM) employs DNA bending to package mitochondrial DNA (mtDNA) into nucleoids and recruit mitochondrial RNA polymerase (POLRMT) at specific promoter sites, light strand promoter (LSP) and heavy strand promoter (HSP). Herein, we characterize the conformational dynamics of TFAM on promoter and non-promoter sequences using single-molecule fluorescence resonance energy transfer (smFRET) and single-molecule protein-induced fluorescence enhancement (smPIFE) methods. The DNA-TFAM complexes dynamically transition between partially and fully bent DNA conformational states. The bending/unbending transition rates and bending stability are DNA sequence-dependent—LSP forms the most stable fully bent complex and the non-specific sequence the least, which correlates with the lifetimes and affinities of TFAM with these DNA sequences. By quantifying the dynamic nature of the DNA-TFAM complexes, our study provides insights into how TFAM acts as a multifunctional protein through the DNA bending states to achieve sequence specificity and fidelity in mitochondrial transcription while performing mtDNA packaging.

Abstract Background Expanding human presence in space through long-duration exploration missions and commercial space operations warrants improvements in approaches for quantifying crew space radiation health risks. Currently, risk assessment models for radiogenic cancer and cardiovascular disease consider age, sex, and tobacco use, but do not incorporate other modifiable (e.g., body weight, physical activity, diet, environment) and non-modifiable individual risk factors (e.g., genetics, medical history, race/ethnicity, family history) that may greatly influence crew health both in-mission and long-term. For example, clonal hematopoiesis of indeterminate potential (CHIP) is a relatively common age-related condition that is an emerging risk factor for a variety of diseases including cardiovascular disease and cancer. CHIP carrier status may therefore exacerbate health risks associated with space radiation exposure. Methods In the present study, published CHIP hazard ratios were used to modify background hazard rates for coronary heart disease, stroke, and hematologic cancers in the National Aeronautics and Space Administration space radiation risk assessment model. The risk of radiation exposure-induced death for these endpoints was projected for a future Mars exploration mission scenario. Results Here we show appreciable increases in the lifetime risk of exposure-induced death for hematologic malignancies, coronary heart disease, and stroke, which are observed as a function of age after radiation exposure for male and female crew members that are directly attributable to the elevated health risks for CHIP carriers. Conclusions We discuss the importance of evaluating individual risk factors such as CHIP as part of a comprehensive space radiation risk assessment strategy aimed at effective risk communication and disease surveillance for astronauts embarking on future exploration missions.

The most crucial blood group system in transfusion medicine is still the ABO system. Any unresolved discrepancy could result in the patient receiving blood that is incompatible and could trigger acute intravascular hemolysis. ABO subgroups are one of the astounding differences in blood grouping. The amount of A and B antigens carried by red blood cells and present in secretion varies depending on the ABO subgroup phenotype. Clinically, A1 and A2 are the two most frequently observed subtypes. Many weaker A subgroups have been described, including A3, Axe, am, and el. This example involves an Indian male donor who was initially misclassified as a Group O individual before being identified as an Ax/Aweak subgroup phenotypically. The next-generation sequencing defined the genotype of this case as ABO*AW.31.01/*O.01.75.

Additive manufacturing (AM), shows promising advancements in layer-based modeling displaying its potential for substantial waste reduction. Out of all the AM methods, the most cost-effective and popular choice for prototyping and making customized parts is fused deposition modeling (FDM). This research investigates how various FDM process parameters specifically layer thickness, raster angle, and printing speed affect the mechanical properties of 3D-printed PETG (polyethylene terephthalate glycol) specimens reinforced with carbon fiber (CF). Optimal settings, including a 0° raster angle, 0.2 mm layer thickness, and 40 mm/s printing speed, enhance both tensile and flexural strength due to improvement in material bonding and alignment. Interestingly, lower values for raster angle, layer thickness, and printing speed also lead to notable improvements in mechanical properties. Contour and interaction plots provide valuable insights into the significant impact of these parameters. The study also explores how different printing speeds influence the mechanical characteristics of CF-reinforced PETG specimens. Furthermore, the comparative analysis demonstrated that incorporating carbon fiber into recycled PET waste materials resulted in an approximately 30% increase in tensile strength. These findings imply that using CF with plastic waste in large-scale industries can pave the way for innovative solutions, enhancing performance and sustainability, especially in the automotive, and defence sectors.

Abstract Background The burden of antimicrobial resistance (AMR) in Latin America is high. Little is known about healthcare workers’ (HCWs) knowledge, attitudes, and perceptions of antimicrobial stewardship (AS), AMR, and antibiotic use (AU) in the region. Methods HCWs from 42 hospitals from 5 Latin American countries were invited to take an electronic, voluntary, anonymous survey regarding knowledge, attitudes, and perceptions of AS, AMR, and AU between March–April 2023. Findings Overall, 996 HCWs completed the survey (52% physicians, 32% nurses, 11% pharmacists, 3% microbiologists, and 2% “other”). More than 90% of respondents indicated optimizing AU was a priority at their healthcare facility (HCF), 69% stated the importance of AS was communicated at their HCF, and 23% were unfamiliar with the term “antibiotic stewardship”. Most (> 95%) respondents acknowledged that appropriate AU can reduce AMR; however, few thought AU (

The present study evaluated the immuno-modulatory effect of intrauterine infusion of Neem oil (twice at 24 h interval) in repeat breeding cows (n=6) suffering with sub-clinical endometritis and compared with untreated control (n=6). There were no changes in the mean blood leucocyte count, lymphocytes (%), neutrophils (%) and monocyte (%) between and within groups. The phagocytic activity of blood neutrophils and monocyte was increased at next estrus compared to that at 0 h and 24 h of treatment in treated cows (NO), while, it did not differ in untreated control. The mean stimulation index (lymphocyte proliferation) was significantly higher at next estrus in NO treated cows compared to untreated control. The endometrial mRNA expression of IL-6 (0.18 fold), IL-1α (0.25 fold) and TNF- α (0.38 fold) were downregulated after the treatment in treated cows, while the mRNA transcript of IL-10 (3.28 fold) was upregulated after the treatment in group NO compared to control. All the cows showed negative endometrial cytology for PMNs after the treatment in NO group. The cervical mucus bacterial load reduced significantly at next estrus in treated cows compared to untreated control as well as after the treatment compared to before the treatment. The first service conception rate was 50% (3/6) in treated cows, while, the corresponding figure in untreated control was 16.67% (1/6). In conclusion, methanolic extract of neem oil may improve the recovery and conception rate in cows with sub-clinical endometritis through its bactericidal and immunomodulatory activity.

Introduction: Accelerating smoking cessation, particularly among young adults, is a national priority for decreasing tobacco-related disease. Healthcare providers play a critical role in delivering tobacco treatment interventions to this population. This study examined associations of demographic and tobacco use characteristics with young adults’ self-reported past-year clinical encounters to identify opportunities to facilitate cessation. Methods: We conducted cross-sectional, secondary analyses on a sample of 831 young adults aged 18–34 participating in the first wave of the National Young Adult Health Survey (NYAHS 2018–2019). Demographic and tobacco use characteristics were participants’ sex, age, race, current cigarette use, and current other tobacco use. Clinical encounter outcomes were past-year self-report of (1) seeing a clinician, (2) being asked about tobacco use, and among those currently smoking, (3) being advised to quit smoking. Results: After adjustment for covariates, women (vs. men) had 2.16 times greater odds of reporting seeing a clinician, while Non-White (vs. White) young adults and those currently (vs. never) smoking had 69% and 47% lower odds. Women and those currently smoking had 2.98 and 2.66 times greater odds, respectively, of being asked about tobacco use. Among those who currently smoked, being not confident (vs. confident) about quitting smoking was associated with 69% lower odds of being advised to quit; those who reported moderate (vs. low) nicotine dependence had 3.11 times higher odds of being advised to quit. Conclusions: Sex, racial, and smoking status differences in young adults’ clinical encounter outcomes suggest multiple opportunities for future smoking prevention and cessation intervention efforts.

Background The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Methods Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. Results A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p

Necrotizing fasciitis (NF) is a rare but life-threatening disease characterized by rapidly spreading inflammation and subsequent necrosis of the fascial planes and surrounding tissues. Limited literature has described NF as involving an adjacent solid organ beyond fascial planes that has required its removal. We present a case of a 25-year-old white female who underwent a cesarean section and subsequently developed NF involving her uterus and abdominal wall that necessitated a total abdominal hysterectomy, serial surgical debridement of necrotic tissue, and wound vacuum assisted closure (VAC) placement. Her pathology report described her uterus infiltrated by polybacteria, confirming a diagnosis of NF. Despite NF's progressive nature and potential lethality, NF can be challenging to diagnose clinically due to a lack of pathognomonic signs and symptoms. However, early detection of NF with the aid of Laboratory Risk Indicator for Necrotizing Fasciitis score calculation using laboratory values such as white blood cell count, hemoglobin, sodium, glucose, serum creatinine, and C-reactive protein is critical for optimal patient outcomes. A multidisciplinary team approach is vital in treating these patients to debride necrotizing tissue and control the potential sequelae from the infection, particularly for postpartum patients.

Preclinical models of large‐vessel occlusion (LVO) stroke play an important role in testing novel thrombolytic and neuroprotective agents, as well as assessing endovascular devices for endovascular thrombectomy. Depending on the modality used to model LVO stroke, different aspects of human stroke pathophysiology can be recapitulated. Thus, variables including size and region of the occlusion, composition of the clot, and degree of reperfusion can be controlled. We conducted a thorough literature review of all the preclinical models of stroke used currently. We searched for studies using the PubMed database and included original studies, reviews, systematic reviews, and meta‐analyses. In this review, we describe the considerations in choosing a preclinical model of LVO stroke. We provide an overview of available small‐ and large‐animal LVO stroke models that can be used in stroke research as well as the benefits and limitations of each. We then discuss the current outcome measures that can be evaluated through these models, in terms of both tissue damage and behavioral outcome. We also discuss the advantages and disadvantages of each animal model. Finally, based on this summary, we propose that mice represent the most versatile small‐animal LVO model and dogs are the most appropriate large‐animal LVO stroke model to translate candidate drugs and devices into clinical trials.

Abstract Chronic HIV-1 infection is characterized by T-cell dysregulation that is partly restored by antiretroviral therapy. Autophagy is a critical regulator of T-cell function. Here, we demonstrate a protective role for autophagy in HIV-1 disease pathogenesis. Targeted analysis of genetic variation in core autophagy gene ATG16L1 reveals the previously unidentified rs6861 polymorphism, which correlates functionally with enhanced autophagy and clinically with improved survival of untreated HIV-1-infected individuals. T-cells carrying ATG16L1 rs6861(TT) genotype display improved antiviral immunity, evidenced by increased proliferation, revamped immune responsiveness, and suppressed exhaustion/immunosenescence features. In-depth flow-cytometric and transcriptional profiling reveal T-helper-cell-signatures unique to rs6861(TT) individuals with enriched regulation of pro-inflammatory networks and skewing towards immunoregulatory phenotype. Therapeutic enhancement of autophagy recapitulates the rs6861(TT)-associated T-cell traits in non-carriers. These data underscore the in vivo relevance of autophagy for longer-lasting T-cell-mediated HIV-1 control, with implications towards development of host-directed antivirals targeting autophagy to restore immune function in chronic HIV-1 infection.

Endoscopic retrograde cholangiopancreatography (ERCP) has continued to develop over recent decades with regard to both indications for its use and improvements in technique. The most common complication is post-ERCP pancreatitis (PEP) with incidence rates being reported at ~10%. The exact mechanism of PEP is unknown but is likely multifactorial with papillary edema contributing to the activation of the inflammatory cascade playing an important role. Selected risk factors include patient-related factors (female sex, younger age, sphincter of Oddi dysfunction, and history of PEP) and procedure-related factors (difficult cannulation, multiple pancreatic duct guidewire passes, pancreatic acinarization, multiple pancreatic duct contrast injections, and precut sphincterotomy). Several preventative prophylactic strategies have been posited; however, current guidelines recommend the use of rectal non-steroidal anti-inflammatory drugs (NSAIDs), aggressive intravenous (IV) fluid hydration, and pancreatic duct stents. Appropriate patient selection and the use of noninvasive imaging modalities for diagnosis of pancreaticobiliary abnormalities is a key aspect in prevention. Future studies continue to explore various pharmacologic, procedure-related, and combination strategies for prevention and will be important as the use of ERCP continues to grow.

Abstract The high potential of siRNAs to silence oncogenic drivers remains largely untapped due to the challenges of tumor cell delivery. Here, divalent lipid-conjugated siRNAs are optimized for in situ binding to albumin to improve pharmacokinetics and tumor delivery. Systematic variation of the siRNA conjugate structure reveals that the location of the linker branching site dictates tendency toward albumin association versus self-assembly, while the lipid hydrophobicity and reversibility of albumin binding also contribute to siRNA intracellular delivery. The lead structure increases tumor siRNA accumulation 12-fold in orthotopic triple negative breast cancer (TNBC) tumors over the parent siRNA. This structure achieves approximately 80% silencing of the anti-apoptotic oncogene MCL1 and yields better survival outcomes in three TNBC models than an MCL-1 small molecule inhibitor. These studies provide new structure-function insights on siRNA-lipid conjugate structures that are intravenously injected, associate in situ with serum albumin, and improve pharmacokinetics and tumor treatment efficacy.

Introduction: Cannabis is one of the most widely used psychoactive substances globally, with an increasing trend in its legalization for both medical and recreational purposes in various countries. While cannabis offers potential therapeutic benefits, its regular use can lead to the development of Cannabis Use Disorders (CUDs). Understanding the epidemiology of CUDs is crucial in assessing the public health burden associated with cannabis use. Methods: Epidemiological parameters of CUDs were assessed using the Global Burden of Disease (GBD) methodology across different age-groups, years, sexes, and locations worldwide from 1990-2019. Results: Globally, for both sexes combined, prevalent cases of CUDs increased steadily from 17.1 million(95%UI=12.7-22.8million) in 1990 to 23.8-million(95%UI=17.8-30.9 million) in 2019. All age-adjusted highest number of incidence observed in High-Income-North-America(HINA)(121/100,000), followed by Australasia(100/100,000), Oceania(83.97/100,000), Tropical Latin America(69.59/100,000). Globally, age-standardized disability-adjusted life years rate(ASDR) observed higher in HINA, followed by Australasia, and Western-Europe. In male, all-age incidence counts increased from 1.7 million(95%UI=1.3-2.4million) in 1990 to 2.4 million(95%UI=1.8-3.2 million) in 2019. The highest annual percentage of change in age-standardized incidence rate(ASIR) was found in East-Asia (22%) followed by Middle-East and North-Africa(MENA)(15%). The age group of 15-24 years exhibited the highest burden of CUDs. Conclusion: The widespread occurrence of CUDs on a global scale poses a substantial challenge to public health. Understanding the impact of CUDs and implementing evidence-based interventions is crucial in mitigating the associated individual, societal, and economic burdens. Continued research, collaboration, and knowledge dissemination are essential to inform policies, prevention efforts, and treatment strategies aimed at addressing CUDs on a global-scale.

Obesity promotes metabolic diseases such as type 2 diabetes and cardiovascular disease. PKCδI is a serine/threonine kinase which regulates cell growth, differentiation, and survival. Caspase-3 cleavage of PKCδI releases the C-terminal catalytic fragment (PKCδI_C), which promotes inflammation and apoptosis. We previously demonstrated an increase in PKCδI_C in human obese adipose tissue (AT) and adipocytes. Subsequently, we designed a small molecule drug called NP627 and demonstrated that NP627 specifically inhibited the release of PKCδI_C in vitro. Here, we evaluate the in vivo safety and efficacy of NP627 in a diet-induced obese (DIO) mouse model. The results demonstrate that NP627 treatment in DIO mice increased glucose uptake and inhibited the cleavage of PKCδI_C in the AT as well as in the kidney, spleen, and liver. Next, RNAseq analysis was performed on the AT from the NP627-treated DIO mice. The results show increases in ADIPOQ and CIDEC, upregulation of AMPK, PI3K-AKT, and insulin signaling pathways, while inflammatory pathways were decreased post-NP627 administration. Further, levels of lncRNAs associated with metabolic pathways were affected by NP627 treatment. In conclusion, the study demonstrates that NP627, a small-molecule inhibitor of PKCδI activity, is not toxic and that it improves the metabolic function of DIO mice in vivo.

The orchid genus Dipodium R.Br. (Epidendroideae) comprises leafy autotrophic and leafless mycoheterotrophic species, with the latter confined to sect. Dipodium. This study examined plastome degeneration in Dipodium in a phylogenomic and temporal context. Whole plastomes were reconstructed and annotated for 24 Dipodium samples representing 14 species and two putatively new species, encompassing over 80% of species diversity in sect. Dipodium. Phylogenomic analysis based on 68 plastid loci including a broad outgroup sampling across Orchidaceae found that sect. Leopardanthus is the sister lineage to sect. Dipodium. Dipodium ensifolium, the only leafy autotrophic species in sect. Dipodium, was found to be a sister to all leafless, mycoheterotrophic species, supporting a single evolutionary origin of mycoheterotrophy in the genus. Divergence-time estimations found that Dipodium arose ca. 33.3 Ma near the lower boundary of the Oligocene and that crown diversification commenced in the late Miocene, ca. 11.3 Ma. Mycoheterotrophy in the genus was estimated to have evolved in the late Miocene, ca. 7.3 Ma, in sect. Dipodium. The comparative assessment of plastome structure and gene degradation in Dipodium revealed that plastid ndh genes were pseudogenised or physically lost in all Dipodium species, including in leafy autotrophic species of both Dipodium sections. Levels of plastid ndh gene degradation were found to vary among species as well as within species, providing evidence of relaxed selection for retention of the NADH dehydrogenase complex within the genus. Dipodium exhibits an early stage of plastid genome degradation, as all species were found to have retained a full set of functional photosynthesis-related genes and housekeeping genes. This study provides important insights into plastid genome degradation along the transition from autotrophy to mycoheterotrophy in a phylogenomic and temporal context.

Background. Living donation is paramount for expanding the donor pool. The aim of this study was to assess changes over time in self-reported mental health of living donor kidney applicants in efforts to inform patient-centered discussions with potential donors. Methods. Kidney donor applications from 2017 through 2021 were compiled. Data included age, gender, race, ethnicity, applicant–recipient relationship, medical history, and medications. Trends over time were analyzed and post hoc analyses were performed. Results. During the study period, 2479 applicants to the living donor kidney program were evaluated; 73% of applicants were female individuals. More than half of applicants were not related to their intended recipient; this fraction increased from 46% in 2017 to 58% in 2021 (P

Objective: Atypical Parkinsonian syndrome (APS) describes a heterogeneous group of disorders mimicking the clinical presentation of Parkinson disease (PD) but with disparate natural history and pathophysiology. While retinal markers of PD are increasingly described, APS has been afforded less attention possibly owing to its lower prevalence. Here, we investigate retinal morphological differences in individuals with APS in a large real world cohort. Methods: We conducted a cross-sectional analysis of the AlzEye study, a retrospective cohort where ophthalmic data of individuals attending Moorfields Eye Hospital between January 2008 and March 31st 2018 (inclusive) has been linked with systemic disease data through national hospital admissions. Retinal features were extracted from macula-centered color fundus photography (CFP) and optical coherence tomography (OCT) and compared between individuals with APS and those unaffected. Individuals with idiopathic PD were excluded. Retinal neural and vascular features were measured using automated segmentation and analyzed with multivariable-adjusted regression models. Results: Among a cohort of 91,170 patients, there were 51 patients with APS and 91,119 controls. Individuals with APS were older and more likely to have hypertension and diabetes mellitus. After adjusting for age, sex, hypertension and diabetes melitus, individuals with APS had a thinner ganglion cell-inner plexiform layer (-3.95 microns, 95% CI: −7.53, −0.37, p = 0.031) but no difference in other retinoneural or retinovascular indices. Optic nerve cup-to-disc ratio was similar between groups. Conclusion: Our cross-sectional analysis of the AlzEye cohort reveals distinct retinal morphological characteristics in APS compared to healthy controls. The study notably identifies a thinner ganglion cell-inner plexiform layer in APS patients, without accompanying changes in the inner nuclear layer or significant alterations in retinovascular indices and optic nerve cup-disc ratio. These changes are distinct from those observed in PD, where thinning of the inner nuclear layer (INL) is a characteristic feature. Significance: These findings demonstrate a retinal phenotype in APS, markedly different from both healthy controls and idiopathic Parkinson's disease, highlighting the potential of retinal imaging in differentiating neurodegenerative disorders. By establishing a distinct retinal phenotype for APS, our findings underscore the potential of retinal imaging as a valuable, non-invasive diagnostic tool. This advancement is particularly significant for enhancing diagnostic accuracy, facilitating early detection, and offering a window into the underlying disease mechanisms in APS, thereby aiding in the development of targeted therapeutic interventions and personalized patient care strategies.

Dengue virus (DENV), transmitted by infected mosquitoes, is a major public health concern, with approximately half the world’s population at risk for infection. Recent decades have increasing incidence of dengue-associated disease alongside growing frequency of outbreaks. Although promising progress has been made in anti-DENV immunizations, post-infection treatment remains limited to non-specific supportive treatments. Development of antiviral therapeutics is thus required to limit DENV dissemination in humans and to help control the severity of outbreaks. Dendritic cells (DCs) are amongst the first cells to encounter DENV upon injection into the human skin mucosa, and thereafter promote systemic viral dissemination to additional human target cells. Autophagy is a vesicle trafficking pathway involving the formation of cytosolic autophagosomes, and recent reports have highlighted the extensive manipulation of autophagy by flaviviruses, including DENV, for viral replication. However, the temporal profiling and function of autophagy activity in DENV infection and transmission by human primary DCs remains poorly understood. Herein, we demonstrate that mechanisms of autophagosome formation and extracellular vesicle (EV) release have a pro-viral role in DC-mediated DENV transmission. We show that DENV exploits early-stage canonical autophagy to establish infection in primary human DCs. DENV replication enhanced autophagosome formation in primary human DCs, and intrinsically-heightened autophagosome biogenesis correlated with relatively higher rates of DC susceptibility to DENV. Furthermore, our data suggest that viral replication intermediates co-localize with autophagosomes, while productive DENV infection introduces a block at the late degradative stages of autophagy in infected DCs but not in uninfected bystander cells. Notably, we identify for the first time that approximately one-fourth of DC-derived CD9/CD81/CD63+ EVs co-express canonical autophagy marker LC3, and demonstrate that DC-derived EV populations are an alternative, cell-free mechanism by which DCs promote DENV transmission to additional target sites. Taken together, our study highlights intersections between autophagy and secretory pathways during viral infection, and puts forward autophagosome accumulation and viral RNA-laden EVs as host determinants of DC-mediated DENV infection in humans. Host-directed therapeutics targeting autophagy and exocytosis pathways thus have potential to enhance DC-driven resistance to DENV acquisition and thereby limit viral dissemination by initial human target cells following mosquito-to-human transmission of DENV.

Background Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known.Objectives To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors.Methods In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health.Results From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86).Conclusion Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need.Trail registration number ISRCTN10980107.

ObjectiveThe COVID-19 pandemic was associated with a reduction in the incidence of myocardial infarction (MI) diagnosis, in part because patients were less likely to present to hospital. Whether changes in clinical decision making with respect to the investigation and management of patients with suspected MI also contributed to this phenomenon is unknown.MethodsMulticentre retrospective cohort study in three UK centres contributing data to the National Institute for Health Research Health Informatics Collaborative. Patients presenting to the Emergency Department (ED) of these centres between 1st January 2020 and 1st September 2020 were included. Three time epochs within this period were defined based on the course of the first wave of the COVID-19 pandemic: pre-pandemic (epoch 1), lockdown (epoch 2), post-lockdown (epoch 3).ResultsDuring the study period, 10,670 unique patients attended the ED with chest pain or dyspnoea, of whom 6,928 were admitted. Despite fewer total ED attendances in epoch 2, patient presentations with dyspnoea were increased (p

BackgroundPatients with advanced cancer undergoing chemotherapy experience significant symptoms and declines in functional status, which are associated with poor outcomes. Remote monitoring of patient-reported outcomes (PROs; symptoms) and step counts (functional status) may proactively identify patients at risk of hospitalization or death. ObjectiveThe aim of this study is to evaluate the association of (1) longitudinal PROs with step counts and (2) PROs and step counts with hospitalization or death. MethodsThe PROStep randomized trial enrolled 108 patients with advanced gastrointestinal or lung cancers undergoing cytotoxic chemotherapy at a large academic cancer center. Patients were randomized to weekly text-based monitoring of 8 PROs plus continuous step count monitoring via Fitbit (Google) versus usual care. This preplanned secondary analysis included 57 of 75 patients randomized to the intervention who had PRO and step count data. We analyzed the associations between PROs and mean daily step counts and the associations of PROs and step counts with the composite outcome of hospitalization or death using bootstrapped generalized linear models to account for longitudinal data. ResultsAmong 57 patients, the mean age was 57 (SD 10.9) years, 24 (42%) were female, 43 (75%) had advanced gastrointestinal cancer, 14 (25%) had advanced lung cancer, and 25 (44%) were hospitalized or died during follow-up. A 1-point weekly increase (on a 32-point scale) in aggregate PRO score was associated with 247 fewer mean daily steps (95% CI –277 to –213; P

ObjectiveThe aim of our study was to delineate the differences in demographics, comorbidities, and hospital outcomes by eating disorder types in adolescents and transitional-age youth (15–26 years), and measure the association with psychiatric comorbidities.MethodsWe conducted a cross-sectional study using the nationwide inpatient sample (2018–2019) and included 7,435 inpatients (age 12–24 years) with a primary diagnosis of eating disorders: anorexia nervosa (AN, 71.7%), bulimia nervosa (BN, 4.7%), avoidant/restrictive food intake disorder (ARFID, 9.5%), and other. We used independent logistic regression models controlled for demographics to evaluate the adjusted odds ratio association of comorbidities with eating disorder types.ResultsThe mean age of BN inpatients was 17.5 years, which was significantly higher compared to the total number of inpatients with eating disorders (15.9 years). Approximately four-fifths of the inpatients with AN and BN were female patients whereas ARFID was seen in a higher proportion of male patients (32.6% vs. 13.7% overall). Anxiety (57.5%) and depressive (47.3%) disorders were prevalent in the total number of inpatients with eating disorders, with suicidal behaviors seen significantly higher in BN (25.7% vs. 12.9% overall). The likelihood of obsessive compulsive–related disorder was higher in all eating disorder types, i.e., AN (OR 2.14), BN (OR 1.79), and ARFID (OR 1.74); however, anxiety (OR 1.52) and neurodevelopmental (OR 1.70) disorders were significantly higher in ARFID. In terms of hospital outcomes, inpatients with ARFID had a longer mean length of stay (13.7 days vs. 8.4 days in BN) and higher mean total charges ($87,747 vs. $44,882 in BN).ConclusionOur findings identify notable demographic and clinical distinctions within inpatients diagnosed with AN, BN, and ARFID. Specifically, inpatients with BN belonging to older age brackets manifest elevated occurrences of depressive disorders and suicidal tendencies. ARFID is linked to prolonged hospitalization and increased costs, underscoring distinctive complexities in care. This highlights the significance of personalized interventions that account for demographic variations and psychiatric comorbidities, aiming to improve outcomes for diverse populations affected by eating disorders.

Blood cell (BC) classification holds significant importance in medical diagnostics as it enables the identification and differentiation of various types of BCs, which is crucial for detecting specific infections, disorders, or conditions, and guiding appropriate treatment decisions. Accurate BC classification simplifies the evaluation of immune system performance and the diagnosis of various ailments such as infections, leukemia, and other hematological disorders. Deep learning algorithms perform excellently in the automated identification and differentiation of various types of BCs. One of the advanced deep learning models, EfficientNet has shown remarkable performance with limited datasets, another model Swin Transformer’s capability to capture intricate patterns and features makes it more accurate, albeit with limitations due to its large number of parameters. However, medical image datasets are often limited, necessitating a solution that balances accuracy and efficiency. To address this, we propose a novel hybrid model, EfficientSwin, which combines Swin Transformer’s and EfficientNet’s strengths. We first fine-tuned the Swin Transformer on a blood cell dataset comprising wihite blood cells, red blood cells and platelets, achieving promising outcomes. Subsequently, our hybrid model, EfficientSwin, outperformed the standalone Swin Transformer, achieving an impressive 98.14% accuracy in BCs classification. Furthermore, we compared our approach with previous research on white blood cell datasets, showcasing the superiority of EfficientSwin in accurately classifying blood cells. We also employed saliency maps for a visual representation of our classification results, further illustrating the efficacy of our approach.

Introduction The use of smart technology in supporting older adults is a growing field of research. However, there is little qualitative research on the experiences of patients utilizing this technology, particularly those attending psychiatry services. Objectives To explore the experiences of staff and patients utilizing smart-hubs implemented during the Covid-19 pandemic to provide remote audio/visual communication and smart AI personal assistant technology for the management of patients in a rural Psychiatry of Old Age service. Methods Smart hubs were installed in patient homes and in the Psychiatry of Old Age base during the Covid-19 pandemic when lockdown restrictions limited in-person service provision. Patients and staff utilized the smart hubs for its assistive technology and to engage with each other. Semi-structured qualitative interviews were conducted of 10 staff and 15 patients at 6-12 months following the introduction of the smart hubs and thematic analysis was conducted to generate themes. Results Three themes were generated from the thematic analysis: 1) Openness to SMART hub technology, 2) Getting set-up and 3) Keeping SMART. The majority of participants did not have much experience using smart technology prior to the intervention. However, many participants reported that they would be comfortable using technology. The Covid-19 pandemic contributed to the rapid adoption of this intervention within the service with mixed views regarding the smart hub prior to implementation. The role of key individuals such as staff and family was highlighted in supporting older persons with setting-up the smart hub. Technical needs included the need for a strong internet connection and technical limitations were driven by privacy, cost and regional considerations. Many patients were able to utilize the smart hub independently to access interests, therapeutic activities and as a memory aid. The smart hub offered a novel way to connect to services and families and was also seen as a companion by some patients and staff to help address loneliness and isolation. The majority of participants found the use of smart hubs acceptable and were willing to utilize the smart hub in the future as an adjunct to face to face psychiatric interventions. However, suggestions for future use included the need for additional training as users felt that there was more they could do with the smart hub, continued support to manage any challenges and improved information leaflets to better engage users. Conclusions Smart hub technology offers an alternate means of providing remote and inclusive psychiatric care to older patients unable to access services in person and at risk of deterioration without intervention in the community. Disclosure of Interest None Declared

ABSTRACT Importance Reported coronavirus disease 2019 (COVID‐19) pandemic effects on pediatric trauma have been variable. Objective We investigated the characteristics of pediatric trauma including alcohol use during the pandemic at our urban trauma center. Methods The trauma database of our adult level 1 trauma center was queried for all pediatric (age ≤ 18 years) patients presenting between March 1, 2020, and October 30, 2020. Data from 2017 to 2019 served as a control. Variables analyzed included demographics, mechanisms, injury severity, hospitalization characteristics, and positive blood alcohol. Results Pandemic pediatric trauma volumes increased by 67.5% (330/year vs. 197/year). Pandemic patients were younger (median age 13 vs. 14 years, P = 0.011), but similar in gender, ethnicity, severity, hospital length of stay, mortality, and rates of penetrating injury. Falls doubled (79/year vs. 34/year) and shifted away from high falls >6 meters (0% vs. 7.9%) to moderate falls 1–6 meters (58.2% vs. 51.5%) (P = 0.028). Transportation injury rates were similar however mechanisms shifted from motor vehicle crashes (−13.5%) towards recreational vehicles including motorcycles (+2.1%), all‐terrain vehicles (+8.6%), and bicycles (+3.8%) (P = 0.018). Pediatric‐positive blood alcohol was significantly higher (11.2% vs. 5.1%, P < 0.001), especially for ages 14–18 years (21.7% vs. 9.5%, P < 0.001). Interpretation Pediatric trauma volumes during the COVID‐19 pandemic increased. Pandemic patients had more recreational vehicle injuries and higher rates of positive blood alcohol. This suggests an increased need for alcohol assessment and targeted interventions in the pediatric population during pandemics or periods of school closures.

An experiment was conducted at the Centre for Millets Research, Sardarkrushinagar Dantiwada Agricultural University, Deesa during kharif,2022 to estimate general and specific combining ability effects and components of genetic variance for yield and shoot fly resistance attributing traits in sorghum. The mean sum of squares due to general and specific combining ability was found highly significant for all the studied characters. The estimates of σ2gca/σ2sca revealed preponderance of non-additive type of gene action in the expression of yield and shoot fly resistance associated characters. Considering gca effect the parents SWARNA, GJ 43 and GNJ 1 revealed significantly superior gca value and were identified as a good general combiner for yield contributing characters. The parents IS 18551 and IS 2205 were good general combiners for shoot fly resistance attributes. The crosses IS 18551 × SWARNA, GJ 43 × GNJ 1 and IS 2205 × SWARNA for grain yield per plant recorded the highest sca effects which involved poor × good; good × good and poor × good combination, respectively. The cross, IS 18551 × IS 2205 showed significant desirable sca effects for almost all the characters related to shoot fly resistance, viz., seedling vigour, seedling glossiness and shoot fly dead heart at 14th, 21st and 28th days after emergence (DAE).The regression of Wr on Vr was desirable and near unity for seedling vigour, seedling glossiness, days to flowering, total plant height, shoot fly dead heart at 14 DAE, shoot fly dead heart at 21 and 28 DAE, hydrocyanic acid content, grain yield per plant, protein content and total phenol content. The regression line intercepted Wr axis below the origin indicating over dominance for total plant height, shoot fly dead heart at 14 DAE, hydrocyanic acid content and total phenol content. The component D was significant for all the traits suggesting predominance of additive gene effects. The estimates H1 and H2 were significant for all the traits except days to flowering. The magnitude of non-additive (H1) component was higher than additive (D) component for all the traits except seedling vigour which showed more important role of over dominance. In Wr-Vr graph scattering of parental array point along the regression line for the traits hydrocyanic acid content, crude protein content and total phenol content revealed significant genetic diversity among the parents for the above traits.