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Angel N Desai,1,2 Amir M Mohareb,3– 6 Naomi Hauser,1 Aula Abbara7 1Department of Internal Medicine, Division of Infectious Diseases, University of California Davis Medical Center, Sacramento, CA, USA; 2Global Migration Center, University of California Davis, Davis, CA, USA; 3Department of Medicine, Harvard Medical School, Boston, MA, USA; 4Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; 5Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA; 6Center for Global Health, Massachusetts General Hospital, Boston, MA, USA; 7Department of Infection, Imperial College, London, UKCorrespondence: Angel N DesaiDepartment of Internal Medicine, Division of Infectious Diseases, University of California Davis, Sacramento, CA, USATel +1 9167340168Fax +1 251 333115250Email andesai@ucdavis.eduAbstract: Antimicrobial resistance (AMR) is of increasing global concern. Human mobility is one factor that has recently been associated with AMR, though the extent of its impact has not yet been well established due to the limited availability of rigorous data. This review examines the existing literature regarding various types of human mobility including short-term travelers, forcibly displaced persons, migrant populations, and their association with global rates of AMR.Keywords: antimicrobial resistance, migrant, refugee, displaced person, traveler, mobility

A case study of implementing solar powered infrastructure with grid connectivity, exemplifying the integration of renewable energy solutions in healthcare facilities. The study examines the design, implementation, benefits, and challenges faced during the transformation of a conventional energy based hospital into a sustainable, eco-friendly institution. By leveraging solar photovoltaic (PV) technology and grid-tied systems, the hospital achieves significant energy and financial savings, reduced carbon emissions, and enhanced energy resilience. The findings from this case study provide valuable insights for healthcare institutions seeking to adopt sustainable practices and contribute to a greener future.

Distributed arrays of ground-based instruments can help advance observations and improve understanding of space weather. The implementation of an array of sensors can be constrained, however, by the high cost of commercial instruments and the availability of Internet and power. Additionally, distributed observations require sensors that can be easily deployed and maintained. As part of an effort to expand the breath of skills of physics students while increasing literacy about space weather, a team of undergraduates was formed and tasked with designing, building, and testing an autonomous platform for ionospheric observations using ScintPi 3.0. ScintPi 3.0 is a low-cost ionospheric scintillation and total electron content (TEC) monitor. The design led to a platform that employs cellular-based Internet connectivity as well as solar and battery power. A fully functional prototype was built and deployed near Dallas, USA (32.9° N, 96.4° W). Results show that the platform can run for 232 hours using battery only or indefinitely when connected to the selected solar photovoltaic panel. For system monitoring, LTE functionality enables near real-time updates of the systems’ health and remote shell access. Examples of observations made by the prototype are presented, including the detection of ionospheric effects caused by a space weather event. Additionally, the potential of the system for research, education, and citizen science initiatives are discussed.

During the last 20 years at least 23 cases of motor neuron disease have been reported in HIV-1 seropositive patients. In this report we describe the clinical picture of a young man with HIV-1 clade C infection and flail arm-like syndrome, who we were able to follow-up for a long period. We investigated and prospectively monitored a 34-year-old man with features of flail arm syndrome, who developed the weakness and wasting 1 year after being diagnosed with HIV-1 infection after a routine blood test. He presented in 2003 with progressive, symmetrical wasting and weakness of the proximal muscles of the upper limb of 2 years′ duration. He had severe wasting and weakness of the shoulder and arm muscles. There were no pyramidal signs. He has been on HAART for the last 4 years and the weakness or wasting has not worsened. At the last follow-up in July 2007, the patient had the same neurological deficit and no other symptoms or signs of HIV-1 infection. MRI of the spinal cord in 2007 showed characteristic T2 hyperintense signals in the central part of the spinal cord, corresponding to the central gray matter. Thus, our patient had HIV-1 clade C infection associated with a ′flail arm-like syndrome.′ The causal relationship between HIV-1 infection and amyotrophic lateral sclerosis (ALS)-like syndrome is still uncertain. The syndrome usually manifests as a lower motor neuron syndrome, as was seen in our young patient. It is known that treatment with antiretroviral therapy (ART) stabilizes/improves the condition. In our patient the weakness and atrophy remained stable over a period of 3.5 years after commencing HAART regimen.

Abstract Background Juvenile Fibromyalgia (JFM) is characterized by chronic widespread musculoskeletal pain and approximately 40% of children and adolescents with JFM also suffer from benign joint hypermobility (HM). It is not currently known if the presence of HM affects the pain experience of adolescents with JFM. The objective of this study was to examine whether there were any differences in self-reported pain intensity and physiologic pain sensitivity between JFM patients with and without joint HM. Methods One hundred thirty-one adolescent patients with JFM recruited from four pediatric rheumatology clinics completed a daily visual analogue scale (VAS) pain rating for one week and underwent a standardized 18-count tender point (TP) dolorimeter assessment. Medical records were reviewed for the presence of joint HM. Average pain VAS ratings, tender point count and tender point sensitivity were compared between JFM patients with and without hypermobility (HM+ and HM-). Results Nearly half (48%) the sample of JFM patients were found to be HM+. HM+ and HM- patients did not differ in their self-reported pain intensity. However, HM + patients had significantly greater pain sensitivity, with lower TP thresholds (p = 0.002) and a greater number of painful TPs (p = 0.003) compared to HM- patients. Conclusion The presence of HM among adolescent patients with JFM appears to be associated with enhanced physiologic pain sensitivity, but not self-report of clinical pain. Further examination of the mechanisms for increased pain sensitivity associated with HM, especially in adolescents with widespread pain conditions such as JFM is warranted.

Abstract Background To evaluate the feasibility of image-guided radiotherapy based on helical Tomotherapy to spare the contralateral parotid gland in head and neck cancer patients with unilateral or no neck node metastases. Methods A retrospective review of 52 patients undergoing radiotherapy for head and neck cancers with image guidance based on daily megavoltage CT imaging with helical tomotherapy was performed. Results Mean contralateral parotid dose and the volume of the contralateral parotid receiving 40 Gy or more were compared between radiotherapy plans with significant constraint (SC) of less than 20 Gy on parotid dose (23 patients) and the conventional constraint (CC) of 26 Gy (29 patients). All patients had PTV coverage of at least 95% to the contralateral elective neck nodes. Mean contralateral parotid dose was, respectively, 14.1 Gy and 24.7 Gy for the SC and CC plans (p p Conclusion Tomotherapy for head and neck cancer minimized radiotherapy dose to the contralateral parotid gland in patients undergoing elective node irradiation without sacrificing target coverage.

Abstract Background CD4+ T lymphocyte counts are the most important indicator of disease progression and success of antiretroviral treatment in HIV infection in resource limited settings. The nationwide reference range of CD4+ T lymphocytes was not available in India. This study was conducted to determine reference values of absolute CD4+ T cell counts and percentages for adult Indian population. Methods A multicentric study was conducted involving eight sites across the country. A total of 1206 (approximately 150 per/centre) healthy participants were enrolled in the study. The ratio of male (N = 645) to female (N = 561) of 1.14:1. The healthy status of the participants was assessed by a pre-decided questionnaire. At all centers the CD4+ T cell count, percentages and absolute CD3+ T cell count and percentages were estimated using a single platform strategy and lyse no wash technique. The data was analyzed using the Statistical Package for the Social Scientist (SPSS), version 15) and Prism software version 5. Results The absolute CD4+ T cell counts and percentages in female participants were significantly higher than the values obtained in male participants indicating the true difference in the CD4+ T cell subsets. The reference range for absolute CD4 count for Indian male population was 381-1565 cells/μL and for female population was 447-1846 cells/μL. The reference range for CD4% was 25-49% for male and 27-54% for female population. The reference values for CD3 counts were 776-2785 cells/μL for Indian male population and 826-2997 cells/μL for female population. Conclusion The study used stringent procedures for controlling the technical variation in the CD4 counts across the sites and thus could establish the robust national reference ranges for CD4 counts and percentages. These ranges will be helpful in staging the disease progression and monitoring antiretroviral therapy in HIV infection in India.

Abstract Background Rho iso-alpha acids (RIAA) from hops have been shown to have anti-inflammatory properties. To understand the mechanisms, we evaluated the effect of RIAA in cell signaling pathways and inflammatory markers using various in vitro models. We also investigated their therapeutic effect in mice with collagen-induced arthritis. Methods The LPS-stimulated RAW 264.7 macrophages were used to evaluate the effect of RIAA on the NF-κB and MAPK signaling pathways; phosphorylation of ERK1/2, p38 and JNK was assessed by western blotting and NF-κB binding by electrophoretic mobility shift assays. Effect on the NF-κB activity was evaluated by the luciferase reporter assays in LPS-stimulated RAW 264.7 cells. GSK-3α/β kinase activity was measured in cell-free assays. The inhibitory effect of RIAA on inflammatory markers was assessed by measuring nitric oxide in LPS-stimulated RAW 264.7 cells, RANKL-mediated TRAP activity in transformed osteoclasts, and TNF-α/IL-1β-mediated MMP-13 expression in SW1353 cells. Mice with collagen-induced arthritis were fed with RIAA for 2 weeks. Symptoms of joint swelling, arthritic index and joint damage were assessed. Results RIAA selectively inhibited the NF-κB pathway while having no effect on ERK1/2, p38 and JNK phosphorylation in LPS-stimulated RAW 264.7 cells. RIAA also inhibited GSK-3α/β kinase activity and GSK-3β dependent phosphorylation of β-catenin in RAW 264.7 cells. In addition, RIAA inhibited NF-κB-mediated inflammatory markers in various cell models, including nitric oxide in LPS-stimulated RAW 264.7 cells, RANKL-mediated TRAP activity in transformed osteoclasts, and TNF-α/IL-1β-mediated MMP-13 expression in SW1353 human chondrosarcoma cells. Finally, in a mouse model of collagen-induced arthritis, RIAA ameliorated joint damage as evidenced by significant reduction of the arthritis index and histology score; at 250 mg/kg-body weight, RIAA had efficacy similar to that of 20 mg/kg-body weight of celecoxib. Conclusion RIAA may have potential as an anti-inflammatory therapeutic.

Abstract A 27 year-old man who presented to the hospital with progressive lower extremity weakness, developed an acute ST elevation myocardial infarction on his second hospital day. Primary angioplasty to the left anterior descending coronary artery was performed. Due to persistent dyspnea, the patient underwent a diagnostic chest computed tomography which confirmed multiple small pulmonary emboli. Laboratory analysis revealed a megaloblastic anemia with a reduced vitamin B12 level and positive titers for antibodies against intrinsic factor, establishing a diagnosis of pernicious anemia. Screening for hypercoaguable markers documented an isolated severely elevated homocysteine levels (105 μmol/l). No other significant risk factors for coronary artery disease including a family history of premature atherosclerosis were identified. This case illustrates the importance of testing for hyperhomocysteinemia as part of a workup for atherothrombotic disease, especially in patients without other significant risk factors. The severity of hyperhomocysteinemia found in our patient is unusual for patients with vitamin B12 malabsorption and raises the question of whether the widely practiced folic acid fortification in the United States may mask or even worsen vitamin B12 deficiency over time, leading to more severe cases of vitamin B12 deficiency and hyperhomocysteinemia than seen in the past.

Abstract Background During the early and mid part of 20th century, several reports described the therapeutic effects of N-methylisatin-β-Thiosemicarbazone (MIBT) against pox viruses, Maloney leukemia viruses and recently against HIV. However, their ability to inhibit flavivirus replication has not been investigated. Hence the present study was designed to evaluate the antiviral activity of 14 MIBT derivatives against Flaviviruses that are prevalent in India such as Japanese Encephalitis Virus (JEV), Dengue-2 (Den-2) and West Nile viruses (WNV). Results Amongst the fourteen Mannich bases of MIBT derivatives tested one compound – SCH 16 was able to completely inhibit in vitro Japanese encephalitis virus (JEV) and West Nile virus (WNV) replication. However no antiviral activity of SCH 16 was noted against Den-2 virus replication. This compound was able to inhibit 50% of the plaques (IC50) produced by JEV and WNV at a concentration of 16 μgm/ml (0.000025 μM) and 4 μgm/ml (0.000006 μM) respectively. Furthermore, SCH 16 at a concentration of 500 mg/kg body weight administered by oral route twice daily was able to completely (100%) prevent mortality in mice challenged with 50LD50 JEV by the peripheral route. Our experiments to understand the mechanism of action suggest that SCH 16 inhibited JEV replication at the level of early protein translation. Conclusion Only one of the 14 isatin derivatives -SCH 16 exhibited antiviral action on JEV and WNV virus infection in vitro. SCH 16 was also found to completely inhibit JEV replication in vivo in a mouse model challenged peripherally with 50LD50 of the virus. These results warrant further research and development on SCH 16 as a possible therapeutic agent.

Abstract Background Of the diverse subtypes of Human Immunodeficiency Virus Type-1 (HIV-1), subtype-C strains cause a large majority of infections worldwide. The reasons for the global dominance of HIV-1 subtype-C infections are not completely understood. Tat, being critical for viral infectivity and pathogenesis, may differentially modulate pathogenic properties of the viral subtypes. Biochemical studies on Tat are hampered by the limitations of the current purification protocols. Tat purified using standard protocols often is competent for transactivation activity but defective for a variety of other biological functions. Keeping this limitation in view, we developed an efficient protein purification strategy for Tat. Results Tat proteins obtained using the novel strategy described here were free of contaminants and retained biological functions as evaluated in a range of assays including the induction of cytokines, upregulation of chemokine coreceptor, transactivation of the viral promoter and rescue of a Tat-defective virus. Given the highly unstable nature of Tat, we evaluated the effect of the storage conditions on the biological function of Tat following purification. Tat stored in a lyophilized form retained complete biological activity regardless of the storage temperature. To understand if variations in the primary structure of Tat could influence the secondary structure of the protein and consequently its biological functions, we determined the CD spectra of subtype-C and -B Tat proteins. We demonstrate that subtype-C Tat may have a relatively higher ordered structure and be less flexible than subtype-B Tat. We show that subtype-C Tat as a protein, but not as a DNA expression vector, was consistently inferior to subtype-B Tat in a variety of biological assays. Furthermore, using ELISA, we evaluated the anti-Tat antibody titers in a large number of primary clinical samples (n = 200) collected from all four southern Indian states. Our analysis of the Indian populations demonstrated that Tat is non-immunodominant and that a large variation exists in the antigen-specific antibody titers. Conclusion Our report not only describes a simple protein purification strategy for Tat but also demonstrates important structural and functional differences between subtype-B and -C Tat proteins. Furthermore, this is the first report of protein purification and characterization of subtype-C Tat.

Abstract Background Bronchodilator response (BDR) is a measure of improvement in airway smooth muscle tone, inhibition of liquid accumulation and mucus section into the lumen in response to short-acting beta-2 agonists that varies among asthmatic patients. MicroRNAs (miRNAs) are well-known post-translational regulators. Identifying miRNAs associated with BDR could lead to a better understanding of the underlying complex pathophysiology. Objective The purpose of this study is to identify circulating miRNAs associated with bronchodilator response in asthma and decipher possible mechanism of bronchodilator response variation. Methods We used available small RNA sequencing on blood serum from 1,134 asthmatic children aged 6 to 14 years who participated in the Genetics of Asthma in Costa Rica Study (GACRS). We filtered the participants into the highest and lowest bronchodilator response (BDR) quartiles and used DeSeq2 to identify miRNAs with differential expression (DE) in high (N = 277) vs. low (N = 278) BDR group. Replication was carried out in the Leukotriene modifier Or Corticosteroids or Corticosteroid-Salmeterol trial (LOCCS), an adult asthma cohort. The putative target genes of DE miRNAs were identified, and pathway enrichment analysis was performed. Results We identified 10 down-regulated miRNAs having odds ratios (OR) between 0.37 and 0.76 for a doubling of miRNA counts and one up-regulated miRNA (OR = 2.26) between high and low BDR group. These were assessed for replication in the LOCCS cohort, where two miRNAs (miR-200b-3p and miR-1246) were associated. Further, functional annotation of 11 DE miRNAs were performed as well as of two replicated miRs. Target genes of these miRs were enriched in regulation of cholesterol biosynthesis by SREBPs, ESR-mediated signaling, G1/S transition, RHO GTPase cycle, and signaling by TGFB family pathways. Conclusion MiRNAs miR-1246 and miR-200b-3p are associated with both childhood and adult asthma BDR. Our findings add to the growing body of evidence that miRNAs play a significant role in the difference of asthma treatment response among patients as it points to genomic regulatory machinery underlying difference in bronchodilator response among patients. Trial registration LOCCS cohort [ClinicalTrials.gov number NCT00156819, Registration date 20050912], GACRS cohort [ClinicalTrials.gov number NCT00021840].

Abstract Objective There is a rising effort for hospital emergency departments (EDs) to offer and expand substance use disorder (SUD) services. This state-wide evaluation studies SUD services offered along the continuum of implementation across Kentucky’s EDs to inform future state efforts to build ED bridge programs. Methods We conducted a mixed-methods study using an online survey of all Kentucky Emergency Department Directors between January and May of 2023. We created a hospital-level dataset which we used to summarize quantitative questions and thematically analyze open-ended responses. Results Our sample included 85 unique respondents (89% of all eligible Kentucky hospitals). Nine (11%) had active bridge programs to initiate opioid use disorder patients on buprenorphine. Respondents reported that the most challenging SUD-related services for EDs to implement were buprenorphine induction for opioid use disorder treatment (n = 36, 42%), referrals to community-based providers (n = 34, 40%), and providing social work services (n = 25, 29%). Respondents noted that the implementation and improvement of screening protocols were needed to better identify patients with SUD, expressed concerns about care continuity, and explicitly conveyed the need and desire for additional supports to provide SUD care. Conclusions The landscape of Kentucky’s ED SUD supports shows several hospitals that offer services along the continuum of SUD care, and highlights the importance of technical assistance and financial resources to ensure the continuum is broadly available. Kentucky’s experience speaks to broader national challenges in supporting SUD in EDs – specifically the need for financial resources, buy-in and education, and creating referral relationships to ensure care continuity.

Anthony Giuffrida,1 Christy Saia-Owenby,2 Chris Andriano,3,* Douglas Beall,4,* Ashley Bailey-Classen,5,* Patrick Buchanan,6,* Ryan Budwany,7,* Mehul J Desai,8,* Ashley Comer,9,* Andrew Dudas,10,* Vinicius Tieppo Francio,11,* Warren Grace,12,* Benjamin Gill,13,* Betsy Grunch,14,* Andrew Goldblum,13,* Rosa A Garcia,15,* David W Lee,16,* Chad Lavender,17,* Marco Lawandy,18,* Lyric Mandell,2,* Robin Mata,19,* Morteza Rabii,20,* Kiran Patel,21,* Raj G Patel,22,* Ankur A Patel,23,* Dawood Sayed,24,* Gurtej Singh,25,* Natalie Strand,26,* Jordan Tate,27,* Michael E Schatman,28 Timothy Deer29 1Cantor Spine Center, Paley Orthopedic and Spine Institute, Fort Lauderdale, FL, USA; 2MOXY Company, Covington, LA, USA; 3Georgia Pain Care, Stockbridge, GA, USA; 4Oklahoma Spine Hospital, Oklahoma City, OK, USA; 5Trinity Pain Medicine Associates, Fort Worth, TX, USA; 6Spanish Hills Interventional Pain Specialists, Camarillo, CA, USA; 7Center for Pain Relief, Charleston Area Medical Center, Charleston, WV, USA; 8International Spine, Pain, and Performance Center, Washington, DC, USA; 9The Spine and Nerve Centers of the Virginias, Charleston, WV, USA; 10Maya & Schnapp, Neurospine and Pain, Memphis, TN, USA; 11Anesthesiology and Pain Medicine, University of Kansas, Kansas City, KS, USA; 12Redefine Healthcare, Orthopedic Pain and Spine Center, Edison, NJ, USA; 13Physical Medicine and Rehabilitation, University of Missouri, Columbia, MO, USA; 14Longstreet Clinic, Gainesville, GA, USA; 15Larkin Hospital Health Systems, Miami, FL, USA; 16Interventional Pain and Spine, Fullerton Orthopedics, Yorba Linda, CA, USA; 17Department of Orthopaedics, Marshall University, Huntington, WV, USA; 18Physical Medicine and Rehabilitation, Montefiore Medical Center, New York, NY, USA; 19Department of Physical Medicine and Rehabilitation, University of Miami, Miami, FL, USA; 20Crimson Pain Management, Overland Park, KS, USA; 21Pain Medicine and Anesthesiology, Northwell Health, New York, NY, USA; 22Central Texas Interventional Pain Doctor, Capitol Pain Institute, Austin, TX, USA; 23Department of Neurological Surgery, UT Southwestern Medical Center, Dallas, TX, USA; 24Department of Pain Medicine and Neurology, University of Kansas Health System, Kansas City, KS, USA; 25Department of Pain Medicine, Rehabilitation, and Pain Medicine, the Center for Advance Orthopaedics, Cantonsville, MD, USA; 26Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Phoenix, AZ, USA; 27Department of Pain Medicine and Physical Medicine and Rehabilitation, Southern Pain and Spine, Jasper, GA, USA; 28Department of Anesthesiology, Perioperative Care, and Pain Medicine at NYU Grossman School of Medicine, New York, NY, USA; 29Department of Pain Management, Spine and Nerve Centers of the Virginias, Charleston, WV, USA*These authors contributed equally to this workCorrespondence: Lyric Mandell, MOXY Company, Covington, LA, USA, Email lyric@moxycompany.comPurpose: The American Society of Pain and Neuroscience (ASPN) identified a significant gap in resources and guidelines that aim to educate healthcare providers for best practices when engaging on social media. As part of the broader initiatives on Spine and Nerve practice, the executive board of ASPN has decided it would be beneficial to include comprehensive guidance for healthcare providers when engaging on social media.Methods: A panel of experts was chosen based on expertise, publications, diversity, and their social media presence. Along with expert guidance, the committee conducted an extensive analysis of peer-reviewed literature in communication and medical journals to determine best practices for healthcare practitioners on social media.Results: Social media messages significantly impact patients’ and colleagues’ perceptions and actions regarding medical issues. As such, providers and their teams must be aware of legal and ethical considerations in healthcare while maintaining a consistent, educational, and digestible persona online.Conclusion: The advancement of communication and medical technologies and systems necessitates continued education and resources to adapt to our rapidly changing media and medical landscape.Keywords: digital communication, social networking sites, healthcare providers, best practices, physician communication, social media, medical marketing, spine

Background: Chronic obstructive pulmonary disease (COPD) is now one of the top three causes of death worldwide. Despite the availability of various kinds of treatments, there is a paucity of data regarding potential treatment for COPD. Aims and Objectives: This study has been carried out to evaluate the effectiveness and safety of treatments used for COPD. Materials and Methods: A prospective, longitudinal, observational study was carried out at a tertiary care teaching hospital. A total of 105 patients were included and divided into two treatment groups: Group budesonide+formoterol (BF) and group fluticasone+salmeterol (FS) based on the treatment they received. Patients’ details were recorded in a pre-defined case record form. Effectiveness was evaluated and compared between the two treatment groups in terms of the number of exacerbations experienced, the mean reduction in COPD assessment test (CAT) score, and the mean change in forced expiratory volume 1 s (FEV1%) at the end of the study period. Safety was assessed by recording adverse drug reactions. Results: Out of a total of 105 patients with COPD, 67 (63.80%) patients belonged to group BF and 38 (36.19%) patients belonged to group FS. Twenty-seven (40.30%) patients from Group BF (n=67) and 18 (47.37%) patients from group FS (n=38) developed exacerbations. No statistically significant difference between group BF and group FS was observed in terms of mean reduction in CAT score (P= 0.17) as well as mean change in FEV1% (P=0.38) from baseline to the end of 6 months of treatment. Conclusion: Our study concludes that inhalational corticosteroids/long-acting beta-agonist combinations such as BF and FS are equally effective in terms of reduction in frequency and severity of exacerbation, reduction in CAT score, and improvement in lung functions (FEV1%).

OBJECTIVES In the realm of acute pain management within emergency departments (EDs), the prevalent reliance on systemic analgesics, notably opioids, presents challenges due to associated risks and suboptimal efficacy. The emerging alternative of ultrasound-guided nerve blocks (USGNBs) has shown promise in prospective studies. However, the safety and efficacy of USGNBs when performed by emergency medicine practitioners remain largely unexplored, necessitating this study to address the research gap. The primary objectives of this study were to assess the efficacy of Emergency physician-performed USGNBs and changes in patient-reported pain (pre- and postnerve block) at 15 and 30 min. In addition, the time taken to perform nerve blocks, type of nerve block, frequency, indications, procedure time, and complications were all studied. METHODS Conducted at a Tertiary Care Teaching Hospital in Pune, India, this single-center, retrospective observational study aimed to evaluate the effectiveness of USGNBs in the ED context. A retrospective analysis covered 274 emergency practitioner-performed USGNBs recorded from January 2022 to December 2023. Participants included consecutive ED patients consenting to nerve blocks, with practitioners utilizing bupivacaine (0.25%) and ropivacaine (0.25%) based on individual preferences. The study systematically recorded patient demographics, block types, indications, complications, and pre- and postpain scores on a Numerical Rating Scale. RESULTS The study demonstrated a significant reduction in pain scores post-USGNB, with an average decrease of 2.9 ± 1.08 at 15 min and 5.8 ± 1.39 at 30 min. Commonly performed blocks included the femoral nerve, fascia iliaca, and serratus anterior, with notable pain relief in fracture management cases. Procedural durations varied, ranging from 2 to 12 min, while four complications were reported, including diaphragmatic paresis and arterial punctures during interscalene nerve block and fascia iliac compartment blocks, respectively. CONCLUSION This extensive study in an academic ED setting supports the proficiency of emergency practitioners in performing USGNBs. The findings emphasize the transformative potential of USGNBs in academic ED pain management, showcasing notable pain reduction and minimal complications. These results advocate for the integration of advanced pain relief techniques into emergency medicine training programs, contributing to a comprehensive approach to acute pain management.

Background Older age and comorbidities are associated with adverse outcomes in patients with coronavirus disease 2019 (COVID-19); however, comprehensive identification of mortality risk factors can further guide disease management. We aimed to analyze predictors of in-hospital mortality in hospitalized COVID-19 patients. Methods This retrospective cohort study included 400 COVID-19 patients admitted between March and December 2020. Demographics, vital signs, medical history, presenting symptoms, laboratory findings, treatments, and outcomes were extracted from the patient’s electronic medical records. Patients were stratified into survivor (n = 300) and nonsurvivor (n = 100) groups. Univariate and multivariate logistic regressions were used to analyze associations between variables and mortality. Results Nonsurvivors were older (mean age 65 vs 45 years) and had more hypertension (60% vs 33%), diabetes (40% vs 20%), chronic obstructive pulmonary disease (20% vs 5%), and chronic kidney disease (15% vs 3%). Shorter symptom onset to admission (7 vs 4 days), lower oxygen saturation (92% vs 96%), lymphopenia, and elevated inflammatory and coagulation markers were also associated with mortality (all P < 0.001). Mechanical ventilation (60% vs 3%) and therapeutic anticoagulation were more common in nonsurvivors (all P < 0.001). Age over 75 years (adjusted odds ratio 5.2), chronic medical conditions, elevated D-dimer, and mechanical ventilation had the strongest independent associations with mortality (P < 0.001). Conclusions Older age, comorbidities such as chronic pulmonary and renal disease, disease severity parameters such as dysregulated inflammatory and coagulation markers, and the need for aggressive interventions predict increased mortality risk in hospitalized COVID-19 patients.

Background Rabies, a zoonotic disease, poses a significant global public health challenge, and post-exposure prophylaxis (PEP) is crucial for prevention. Monoclonal antibodies (mAbs) have emerged as a promising alternative to rabies immunoglobulins due to their high efficacy and standardized manufacturing process. Materials and Methods A prospective, open-label post-marketing surveillance study was conducted with patients of WHO category-III suspected rabid animal bites. TwinRab™, a novel cocktail of docaravimab and miromavimab, was administered at a dosage of 40 IU/kg in and around the wound, along with the anti-rabies vaccine, which was administered intradermal as per Thai Red Cross regimen. Results In this study, 200 subjects received TwinRab™ with a 100% completion rate. Three (1.5%) patients showed solicited local AEs, and two (1%) patients showed solicited systemic AEs, which were resolved after appropriate treatment intervention. The overall tolerability assessment showed positive ratings from doctors (94%) and patients (74%). Conclusion The post-marketing surveillance study demonstrated the safety of TwinRab™ in patients who experienced category-III suspected rabid animal bites, thereby supporting its potential as an alternative option for PEP in the management of animal bite for the prevention of rabies.

Background: Mothers and fathers may experience negative emotions as a result of an unusual early delivery and giving birth to high-risk newborns who require hospitalization in the neonatal intensive care unit (NICU) adds layers of stress on them. Hence, a variety of psychological and emotional services are required. Aim: The aim of this study was to identify common stressors in both parents of preterm children in the NICU and determine the effect of psychological intervention in the form of acceptance and commitment therapy (ACT) on stress in both parents. Materials and Methodology: A total of 60 parents of preterm children were randomly assigned to Intervention Group A and Control Group B. Group A received five sessions of ACT and routine counseling, while Group B received only routine nursing staff counseling. The Parental Stress Scale: Neonatal Intensive Care Unit (PSS: NICU) was used for pre- and postassessments to measure the parents’ stress levels on the 1st and 5th days, respectively. Results: Mothers’ stress levels in the NICU are significantly higher when they have a higher socioeconomic status, a higher education level, and a length of stay of more than 6 days, but significant stress is not found in fathers. ACT, when used along with routine counseling, is effective in reducing stress in both parents. Conclusion: ACT can be combined with routine counseling to help parents cope with depression, anxiety, and stress associated with preterm birth in the NICUs.

Abstract Over the past three decades, there has been increasing interest in miniaturized percutaneous nephrolithotomy (mPCNL) techniques featuring smaller tracts as they offer potential solutions to mitigate complications associated with standard PCNL (sPCNL). However, despite this growing acceptance and recognition of its benefits, unresolved controversies and acknowledged limitations continue to impede widespread adoption due to a lack of consensus on optimal perioperative management strategies and procedural tips and tricks. In response to these challenges, an international panel comprising experts from the International Alliance of Urolithiasis (IAU) took on the task of compiling an expert consensus document on mPCNL procedures aimed at providing urologists with a comprehensive clinical framework for practice. This endeavor involved conducting a systematic literature review to identify research gaps (RGs), which formed the foundation for developing a structured questionnaire survey. Subsequently, a two-round modified Delphi survey was implemented, culminating in a group meeting to generate final evidence-based comments. All 64 experts completed the second-round survey, resulting in a response rate of 100.0%. Fifty-eight key questions were raised focusing on mPCNLs within 4 main domains, including general information (13 questions), preoperative work-up (13 questions), procedural tips and tricks (19 questions), and postoperative evaluation and follow-up (13 questions). Additionally, 9 questions evaluated the experts’ experience with PCNLs. Consensus was reached on 30 questions after the second-round survey, while professional statements for the remaining 28 key questions were provided after discussion in an online panel meeting. mPCNL, characterized by a tract smaller than 18 Fr and an innovative lithotripsy technique, has firmly established itself as a viable and effective approach for managing upper urinary tract stones in both adults and pediatrics. It offers several advantages over sPCNL including reduced bleeding, fewer requirements for nephrostomy tubes, decreased pain, and shorter hospital stays. The series of detailed techniques presented here serve as a comprehensive guide for urologists, aiming to improve their procedural understanding and optimize patient outcomes.

Abstract Membrane proteins often possess critical structural features, such as transmembrane domains (TMs), N-glycosylation, and disulfide bonds (SS bonds), which are essential to their structure and function. Here, we extend the study of the motifs carrying N-glycosylation, i.e. the sequons, and the Cys residues supporting the SS bonds, to the whole human proteome with a particular focus on the Cys positions in human proteins with respect to those of sequons and TMs. As the least abundant amino acid residue in protein sequences, the positions of Cys residues in proteins are not random but rather selected through evolution. We discovered that the frequency of Cys residues in proteins is length dependent, and the frequency of CC gaps formed between adjacent Cys residues can be used as a classifier to distinguish proteins with special structures and functions, such as keratin-associated proteins (KAPs), extracellular proteins with EGF-like domains, and nuclear proteins with zinc finger C2H2 domains. Most importantly, by comparing the positions of Cys residues to those of sequons and TMs, we discovered that these structural features can form dense clusters in highly repeated and mutually exclusive modalities in protein sequences. The evolutionary advantages of such complementarity among the three structural features are discussed, particularly in light of structural dynamics in proteins that are lacking from computational predictions. The discoveries made here highlight the sequence-structure-function axis in biological organisms that can be utilized in future protein engineering toward synthetic biology.

Abstract Cancer genomes are rife with genetic variants; one key outcome of this variation is widespread gain-of-cysteine mutations. These acquired cysteines can be both driver mutations and sites targeted by precision therapies. However, despite their ubiquity, nearly all acquired cysteines remain unidentified via chemoproteomics; identification is a critical step to enable functional analysis, including assessment of potential druggability and susceptibility to oxidation. Here, we pair cysteine chemoproteomics—a technique that enables proteome-wide pinpointing of functional, redox sensitive, and potentially druggable residues—with genomics to reveal the hidden landscape of cysteine genetic variation. Our chemoproteogenomics platform integrates chemoproteomic, whole exome, and RNA-seq data, with a customized two-stage false discovery rate (FDR) error controlled proteomic search, which is further enhanced with a user-friendly FragPipe interface. Chemoproteogenomics analysis reveals that cysteine acquisition is a ubiquitous feature of both healthy and cancer genomes that is further elevated in the context of decreased DNA repair. Reference cysteines proximal to missense variants are also found to be pervasive, supporting heretofore untapped opportunities for variant-specific chemical probe development campaigns. As chemoproteogenomics is further distinguished by sample-matched combinatorial variant databases and is compatible with redox proteomics and small molecule screening, we expect widespread utility in guiding proteoform-specific biology and therapeutic discovery.

Abstract Multiple microtubule-directed activities concentrate on mitotic chromosomes to ensure their faithful segregation. These include couplers and dynamics regulators localized at the kinetochore, the microtubule interface built on centromeric chromatin, as well as motor proteins recruited to kinetochores and chromatin. Here, we describe an in vivo approach in the C. elegans one-cell embryo in which removal of the major microtubule-directed activities on mitotic chromosomes is compared to the selective presence of individual activities. Our approach reveals that the kinetochore dynein module, comprised of cytoplasmic dynein and its kinetochore-specific adapters, is sufficient to biorient chromosomes; by contrast, this module is unable to support congression. In coordination with orientation, the dynein module directs removal of outermost kinetochore components, including dynein itself, independently of the other microtubule-directed activities and kinetochore-localized protein phosphatase 1. These observations indicate that the kinetochore dynein module is sufficient to biorient chromosomes and to direct remodeling of the outer kinetochore in a microtubule attachment state-sensitive manner.

Abstract Background Missing data in confounding variables present a frequent challenge in generating evidence using real-world data, including electronic health records (EHR). Our objective was to apply a recently published toolkit for characterizing missing data patterns and based on the toolkit results about likely missingness mechanisms, illustrate the decision-making process for analyses in an empirical case example. Methods We utilized the Structural Missing Data Investigations (SMDI) toolkit to characterize missing data patterns in the context of a pharmacoepidemiology study comparing cardiovascular outcomes of initiating sodium-glucose-cotransporter-2 inhibitors (SGLT2i) and dipeptidyl peptidase‐4 inhibitors (DPP‐4i) among older adults. The study used a linked EHR-Medicare claims dataset from Duke Health patients (2015–2017), focusing on partially observed confounders from EHR data (HbA1c lab and body mass index [BMI] values). Our analysis incorporated SMDI's descriptive functions and diagnostic tests to explore missingness patterns and determine missingness mitigation approaches. We used findings from these investigations to inform estimation of adjusted hazard ratios comparing the two classes of medications. Results High levels of missingness were noted for important confounding variables including HbA1c (63.6%) and BMI (16.5%). Diagnostic tests resulted in output that described: 1) the distributions of patient characteristics, exposure, and outcome between patients with or without an observed value of the partially observed covariate, 2) the ability to predict missingness based on observed covariates, and 3) estimate if the missingness of a partially observed covariate is differential with respect to the outcome. There was evidence that missingness could be sufficiently described using observed data, which allowed multiple imputation by chained equations using random forests to address missing confounder data in estimating treatment effects. Multiple imputation resulted in improved alignment of effect estimates with previous studies. Conclusions We were able to demonstrate the practical application of the SMDI toolkit in a real-world setting. Application of the SMDI toolkit and the resulting insights of potential missingness patterns can inform the choice of appropriate analytic methods and increase transparency of research methods in handling missing data. This type of approach can inform analytic decision making and may increase our ability to generate evidence from real-world data.

Abstract Background Pregnancy is a known physiological phenomenon characterized by various changes in the body. The physical and physiological changes that occur during pregnancy may impact the body image which may lead to implications such as body image issues or poor eating habits among pregnant women. This study aimed to analyze the body image perception of pregnant women in their third trimester. Methods This cross-sectional survey which involved the administration of a Multidimensional Body Self-Relations Questionnaire (MBSRQ), was conducted among pregnant women between 28 and 40 weeks of gestation in a tertiary care setting in Southern India. Descriptive statistics were used to report the demographic characteristics of the respondents. A one-sample t-test was used to analyze the difference between the present sample scores and the published norms of MBSRQ. Univariate Logistic Regression was done to find the association between the demographic variables and subdomains of MBSRQ. Results The mean age of the respondents (n = 246) was 29.5 years, and the period of gestation was 33.4 weeks. With mean scores of subscales of MSRQ as reference values, a greater proportion of women had higher scores on appearance orientation (52.44%), health evaluation (56.91%), and illness orientation (55.28%). Respondents scored less on appearance evaluation (52.03%) and body areas satisfaction scale (50.41%). The study found that pre-pregnancy BMI, abdominal circumference, and weight gain during pregnancy were associated with appearance orientation, overweight preoccupation, and self-classified weight. Health evaluation was associated with weight gain and Instagram use, while moderate-intensity physical activity during pregnancy was associated with higher health orientation. Conclusion Although pregnant women in our setting during the third trimester were oriented towards their appearance and considered themselves healthy and fit, almost half of the respondents reported dissatisfaction with their changing bodies and appearance. Self-reported physical activity status, body mass index, weight gain, level of education, use of Instagram app, and type of family were factors found to affect pregnant body image perception. Hence, we conclude that body image perception is affected during pregnancy, and healthcare professionals should be aware of this, and the factors associated with it while addressing the health of pregnant women. Clinical trial registration details The study was registered under the Clinical Trials Registry- India: CTRI/2023/08/056524. https://ctri.nic.in/Clinicaltrials/rmaindet.php?trialid=89771&EncHid=39880.12369&modid=1&compid=19 .

Abstract Chronic Limb Threatening Ischemia (CLTI) is a challenging clinical problem associated with high morbidity and mortality. Endovascular interventions have been the cornerstone of treatment whenever possible. It is estimated that CLTI represents

Abstract Post marketing safety surveillance depends in part on the ability to detect concerning clinical events at scale. Spontaneous reporting might be an effective component of safety surveillance, but it requires awareness and understanding among healthcare professionals to achieve its potential. Reliance on readily available structured data such as diagnostic codes risks under-coding and imprecision. Clinical textual data might bridge these gaps, and natural language processing (NLP) has been shown to aid in scalable phenotyping across healthcare records in multiple clinical domains. In this study, we developed and validated a novel incident phenotyping approach using unstructured clinical textual data agnostic to Electronic Health Record (EHR) and note type. It’s based on a published, validated approach (PheRe) used to ascertain social determinants of health and suicidality across entire healthcare records. To demonstrate generalizability, we validated this approach on two separate phenotypes that share common challenges with respect to accurate ascertainment: (1) suicide attempt; (2) sleep-related behaviors. With samples of 89,428 records and 35,863 records for suicide attempt and sleep-related behaviors, respectively, we conducted silver standard (diagnostic coding) and gold standard (manual chart review) validation. We showed Area Under the Precision-Recall Curve of ~ 0.77 (95% CI 0.75–0.78) for suicide attempt and AUPR ~ 0.31 (95% CI 0.28–0.34) for sleep-related behaviors. We also evaluated performance by coded race and demonstrated differences in performance by race differed across phenotypes. Scalable phenotyping models, like most healthcare AI, require algorithmovigilance and debiasing prior to implementation.

Abstract The majority of viruses classified as pandemic threats are enveloped viruses which enter the cell through receptor-mediated endocytosis and take advantage of endosomal acidification to activate their fusion machinery. Here we report that the endosomal fusion of low pH-requiring viruses is highly dependent on TRPM7, a widely expressed TRP channel that is located on the plasma membrane and in intracellular vesicles. Using several viral infection systems expressing the envelope glycoproteins of various viruses, we find that loss of TRPM7 protects cells from infection by Lassa, LCMV, Ebola, Influenza, MERS, SARS-CoV-1, and SARS-CoV-2. TRPM7 ion channel activity is intrinsically necessary to acidify virus-laden endosomes but is expendable for several other endosomal acidification pathways. We propose a model wherein TRPM7 ion channel activity provides a countercurrent of cations from endosomal lumen to cytosol necessary to sustain the pumping of protons into these virus-laden endosomes. This study demonstrates the possibility of developing a broad-spectrum, TRPM7-targeting antiviral drug to subvert the endosomal fusion of low pH-dependent enveloped viruses.

Introduction: In serological testing, determination of ABO grouping requires both antigen typing for A and B antigens and screening of serum or plasma for A and B antibodies. Lack of corroboration between the results of the cell and serum groupings identifies a discrepancy. Analysis of ABO blood group discrepancies was performed to determine the incidence of these discrepancies among healthy blood donors and oncology patients. Materials and methods: ABO discrepancies found during testing of blood samples from blood donors and patients in an oncology centre in the period from January 2015 to December 2018 were analysed. ABO blood grouping was performed using the column agglutination test. Detailed serological workups were carried out to resolve discrepancies. Results: During the study period, a comprehensive analysis was conducted on a large dataset comprising 76,604 blood donor samples and 134,964 patient samples. Of these samples, 117 ABO discrepancies were identified with 13 occurring in blood donor samples and 104 in patient samples. The results demonstrated discrepancies caused by weakened/missing antibodies, weakened/missing antigens, panagglutination and miscellaneous factors in the blood donor samples, with percentages of 0%, 38%, 8%, and 31%, respectively. In patient samples, the percentages were 24%, 27%, 26%, and 15%, respectively. Conclusion: Weakened/missing antigen discrepancies were the prevalent type in both blood donor and patient samples. For accurate blood group reporting and management of transfusion needs of patients, a complete serological workup is vital to resolve any blood group discrepancies.

Introduction: Urban Health Centre is a key place for implementing Routine Immunization program and vaccine storage. The present study evaluated Cold Chain Point (CCP) and logistics related to routine immunization at selected Urban Health Centers (UHCs) in Ahmedabad. Objective: 1. To evaluate the cold chain infrastructure and logistics supporting routine immunization programs at UHC with a focus on assessing the quality and reliability of vaccine storage and handling practices. 2. To assess the knowledge about cold chain among the Vaccine Cold Chain Handlers (VCCHS). Method: In this cross-sectional study, one UHC from each of the seven zones of Ahmedabad city was randomly selected for assessment of Cold Chain management. Knowledge of VCCHs at each UHCs was assessed using semi-structured questionnaire. Analysis was done using Microsoft excel 2019. Results: It was observed that all UHCs were having session plans and logistics estimation. Around 28.5% UHCs were having lack of essential tools, such as Drop Out charts and maps of their catchment areas. Open vials were found without dates and times labelled in 43% of UHCs, and in one UHC, a vaccine vial was found beyond its usable Vaccine vial Monitor (VVM) stage. All the medical officers utilize various strategies to create awareness, with the majority (86%) using interpersonal communication. All Health Care Providers stated Socio-cultural beliefs and fear of side effects as reason for non-utilization of services. Only 42% of Vaccine Cold Chain Handlers (VCCHs) demonstrated complete knowledge about live vaccines. Conclusion: The study highlights certain issues at UHC like maintenance of drop out chart, map of catchment area, training of medical officers on module of immunization, ice-packs arrangement in Deep Freeze, no knowledge of VCCHs about shake test, which indicates lack of efficiency of VCCHs and need of their training.

Abstract The pace of technological advancement is accelerating, and one of the latest developments is the emergence of Augmented Reality (AR) and Mixed Reality (MR) glasses as an extension of smartphones. The key to success lies in innovative research and technology that can reach a wide audience. To ensure a positive user experience, AR/MR glasses must offer interfaces that are easy to use, memorable, and leave a lasting impression. While Nielsen's heuristics are widely accepted as the standard for usability, it is clear that non‐traditional applications require a rethinking of these heuristics to best suit their unique needs. A fresh usability heuristic for augmented and MR applications is designed by combining and modifying the existing models, such as Nielsen's 10 heuristics, Technology Acceptance Model, and Software Usability Measurement Inventory. The resulting framework incorporates 21 main heuristics and 60 sub heuristics. The 21 main heuristics are further grouped into the Norman's cognitive theory model based on the three levels of processing. The industry experts evaluated and validated the usability framework and established a higher level of effectiveness in identifying more usability problems compared with Nielsen's heuristics.

Publication of various clinical studies or trials is very important to researchers, colleges and countries due to various reasons. Medical teachers get promotion on the basis of their teaching experience as well as their research profile and publications. Time to time MCI/NMC issue guidelines for faculty qualification for various post and their future promotions. There was lack of clarity and several temporary indexed journals published articles with higher Article processing charge without any peer review processed. Cloned/predatory journal is harmful not only for students or faculties but also for medical science. Medical science can get harmed by two ways either under reporting data or over reporting/wrong data. To avoid the wrong information and getting real prevalence, cloned/predatory journal should be identified Publication in those journal is always harmful for authors as well as complete society, country and medical world too.

Introduction: The main aim was to do a systematic review on the published studies to determine kidney disease in pre- and post-liver transplant and its determinants of liver transplantation. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (2020) guidelines were followed to conduct this study. All procedures followed the recommendations found in the Cochrane handbook. Full-text studies, acute kidney injury, and chronic kidney disease (CKD) pre- and post-liver transplantation were included in this study. We included papers from PsycINFO, Google Scholar, PubMed, Web of Science, Medline, Embase, Google, and the Cochrane Library in order to identify additional articles, even though the review ultimately covered all research. Results: A total of 884 references were removed because they were duplicates. The preliminary screening removed 201 of the 243 citations from consideration. There were 37 full-text articles considered for inclusion, but only 9 met the criteria; all the nine articles were very high quality. Totally 1846 patients were studied in this review from all the nine articles with an average age of 51.32 years. All articles were single-center prospective and retrospective observational studies. Conclusion: Kidney failure following liver transplantation is a prevalent and life-threatening complication. Complex events before and after LT cause the condition. The Model for End-Stage Liver Disease score-based organ allocation change is largely responsible for its rapid growth. The majority of studies indicated kidney function declined over time. This highlights the importance of monitoring liver transplant patients’ kidney function and CKD symptoms. Delaying or decreasing tacrolimus administration may help kidney functions.

Background: Currently, either Hem-o-lok (HOL) clip or stapler is being used to control the renal vein in laparoscopic right living donor nephrectomy. The study aims to compare the quality of renal vein retrieved using either HOL clip or Endo TA 30 stapler (TAS) in laparoscopic right living donor nephrectomies. Materials and Methods: We retrospectively analyzed the perioperative data of right-living donor nephrectomies performed at our institute. For the venous control, either two HOL clips (15 mm) or an Endo TA-30 stapler (30 mm–2.5 mm, 3 rows of staples) were used. Perioperative variables from both the donor group and corresponding recipients were recorded and analyzed. A Student’s t-test was used to compare. Results: HOL was applied in 48 (n1) and TAS in 78 (n2) donors, for the control of renal vein. The retrieved length of right renal vein was significantly longer in TAS than in HOL (2.28 ± 0.24 vs. 1.76 ± 0.12 cm, P < 0.001). There was no statistically significant difference in warm ischemia time (5.82 ± 0.89 vs. 5.86 ± 0.91 min, P = 0.84), blood loss (103.65 ± 33.00 vs. 103.64 ± 33.62 mL, P = 0.87), and total surgery duration (139.74 ± 25.83 vs. 140.41 ± 26.33 min, P = 0.86) in both the group. Furthermore, there was no statistically significant difference in postoperative diuresis, acute tubular necrosis, and serum creatinine at 3 months (1.01 ± 0.20 vs. 0.97 ± 0.19 mg/dL, P = 0.67) in corresponding recipients. Conclusion: Endo TAS provides a comparatively longer allograft vein along with an edge of the inferior vena cava than the HOL clip.

Abstract Large language models (LLMs) have shown remarkable abilities recently, including passing advanced professional exams and demanding benchmark tests. This performance has led many to suggest that they are close to achieving humanlike or “true” understanding of language, and even artificial general intelligence (AGI). Here, we provide a new open-source benchmark, the Two Word Test (TWT), that can assess semantic abilities of LLMs using two-word phrases in a task that can be performed relatively easily by humans without advanced training. Combining multiple words into a single concept is a fundamental linguistic and conceptual operation routinely performed by people. The test requires meaningfulness judgments of 1768 noun-noun combinations that have been rated as meaningful (e.g., baby boy) or as having low meaningfulness (e.g., goat sky) by human raters. This novel test differs from existing benchmarks that rely on logical reasoning, inference, puzzle-solving, or domain expertise. We provide versions of the task that probe meaningfulness ratings on a 0–4 scale as well as binary judgments. With both versions, we conducted a series of experiments using the TWT on GPT-4, GPT-3.5, Claude-3-Optus, and Gemini-1-Pro-001. Results demonstrated that, compared to humans, all models performed relatively poorly at rating meaningfulness of these phrases. GPT-3.5-turbo, Gemini-1.0-Pro-001 and GPT-4-turbo were also unable to make binary discriminations between sensible and nonsense phrases, with these models consistently judging nonsensical phrases as making sense. Claude-3-Opus made a substantial improvement in binary discrimination of combinatorial phrases but was still significantly worse than human performance. The TWT can be used to understand and assess the limitations of current LLMs, and potentially improve them. The test also reminds us that caution is warranted in attributing “true” or human-level understanding to LLMs based only on tests that are challenging for humans.

Abstract Background Dietary fibers can alter microbial metabolic output in support of healthy immune function; however, the impact of distinct fiber sources and immunomodulatory effects beyond short-chain fatty acid production are underexplored. In an effort to discern the effects of diverse fibers on host immunity, we employed five distinct rodent diets with varying fiber content and source in specific-pathogen-free, gnotobiotic (containing a 14-member synthetic human gut microbiota), and germ-free mice. Results Broad-scale metabolomics analysis of cecal contents revealed that fiber deprivation consistently reduced the concentrations of microbiota-produced B vitamins. This phenomenon was not always explained by reduced biosynthesis, rather, metatranscriptomic analyses pointed toward increased microbial usage of certain B vitamins under fiber-free conditions, ultimately resulting in a net reduction of host-available B vitamins. Broad immunophenotyping indicated that the local gut effector immune populations and activated T cells accumulate in a microbiota-dependent manner. Supplementation with the prebiotic inulin recovered the availability of microbially produced B vitamins and restored immune homeostasis. Conclusions Our findings highlight the potential to use defined fiber polysaccharides to boost microbiota-derived B vitamin availability in an animal model and to regulate local innate and adaptive immune populations of the host. Video abstract.

Abstract Background Extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation (BTT) has expanded considerably, though evidence-based selection criteria and long-term outcome data are lacking. The purpose of this study was to evaluate whether risk factors often used to exclude patients from ECMO BTT—specifically older age and not yet being listed for transplant—are validated by long-term outcomes. Methods To ensure minimum 5-year follow-up, a retrospective cohort study was performed of adult patients actively listed for lung transplantation at a high-volume center and bridged on ECMO between January 2012 and December 2017. Data was collected through January 1, 2023. Results Among 50 patients bridged on ECMO, 25 survived to transplant. Median age at listing was 58 (interquartile range [IQR], 42–65) in the transplanted group and 65 (IQR, 56.5–69) in the deceased group (P = 0.051). One-year, 3-year, and 5-year survival were 88% (22/25), 60% (15/25), and 44% (11/25), respectively, with eight patients still living at the time of review. Median time spent at home during the year post-transplant was 340 days (IQR, 314–355). Older age at listing was a negative predictor of survival on ECMO to transplant (odds ratio 0.92 [95% confidence interval, 0.86–0.99], P = 0.01). Thirteen patients were placed on ECMO prior to being listed and three were listed the same day as ECMO cannulation, with 10/16 transplanted. No significant difference in post-transplant survival was found between patients placed on ECMO prior to listing (n = 10) and those already listed (n = 15) (P = 0.93, log-rank). Serial post-transplant spirometry up to 5 years and surveillance transbronchial biopsy demonstrated good allograft function and low rates of cellular rejection. Conclusions In one of the oldest cohorts of ECMO BTT patients described, favorable survival outcomes and allograft function were observed up to 5 years irrespective of whether patients were previously listed or bridged to decision. Despite inherent limitations to this retrospective, single-center study, the data presented support the feasibility of ECMO BTT in older and not previously listed advanced lung disease patients.

It has been observed that married women refrain from utilizing contraceptive methods owing to a variety of reasons, including postpartum-amenorrhea, side-effects-worries, rarely or never having sex, no contraception while breastfeeding, or frustration with a particular method. The current study sought to investigate the sociodemographic disparities and contributing factors related to married women who are young (15–24 years old) and non-young (25–49 years old) and who do not utilize contemporary contraceptive methods. The research utilized cross-sectional data obtained from the fifth round of the National Family Health Survey (NFHS-5) to explore the determinants of contraceptive non-utilization among 175,652 married women in India. Multiple logistic regression analysis was utilized for the examination. The study found that non-young married females (25-49) had a higher prevalence of not using contemporary contraceptives (72%) compared to young married females (45.8%). The majority of non-users were from the central region (24.4%), followed by the east (17.4%), north-east (17.2%), north (15.9%), south (15.2%), and west region (9.9%). The majority of non-users were non-working and had male and female household heads. Most non-users knew about modern contraceptives but were unaware of family planning on radio and TV. Higher odds ratios in the non-use among married females were found significant among central-region females (OR=2.189, CI: 1.815-2.641), East-region (OR=1.324, CI: 1.148-1.527), South-region (OR=1.262, CI: 1.063-1.497), females who don’t know caste (OR=1.898, CI: 1.176-3.062), females having primary (OR=3.466, CI: 2.889-4.157) and secondary education (OR=2.281, CI: 1.890-2.753), females who used since last birth (OR=1.851, CI: 1.658-2.068) and never used (OR=1.632, CI: 1.474-1.806). The study found that economically disadvantaged females, household heads, and those with multiple children are less likely to avoid birth control methods, while marital status, religion, caste, education, and birth order did not have a significant impact on non-usage. The study highlights sociodemographic disparities in contraceptive use, emphasizing the need to address issues like low education, media exposure, and ignorance towards birth-control practices, and recommends immediate actions to reduce non-use among married females.

Abstract This single-arm phase II non-randomised trial (ACTRN12619001265167) evaluated trastuzumab emtansine in solid cancers with HER2 amplification or mutation detected by comprehensive genomic profiling. The primary objective was objective response (OR), while secondary objectives included the time to progression (TTP) on study to TTP on prior therapy ratio, progression-free survival (PFS) and overall survival (OS). The cohort included 16 tumours with HER2 mutations (group 1) and 16 with HER2 amplification (group 2). After 17 months median follow-up, ORs occurred in 19% of group 1 (1 salivary gland carcinoma (SGC), 2 lung cancers) and 25% of group 2 (3 SGCs, 1 uterine carcinoma). Fourteen of 29 TTP-evaluable patients achieved a TTP ratio ≥1.3, including 10 without an OR. Median PFS and OS were 4.5 (95% CI 2.1–7.0) and 18.2 months (95% CI 8.1-not reached) respectively. Trastuzumab emtansine showed modest ORs and a favourable change in disease trajectory in select HER2-altered solid cancers.

Abstract Electrolysis of D2O may be used as a portable neutron source with numerous applications without the complexity of huge reactor operations. Herein, we report reproducible fast neutron generation by electrolysis of D2O using palladium cathode and platinum anode, which was detected with diamond detector, gas filled 3He detectors after thermalisation with high density polythene, as well as novel epoxy resin and CR-39 detectors. Notably, a highly reproducible neutron generation at electrochemical surfaces of palladium electrode was observed and signature transmutation via Pd (d, n) Ag was corroborated. This was further explained using a theoretical model based on second order quantum perturbation theory.

Abstract Physical activity or structured exercise is beneficial in a wide range of circumstances. Nevertheless, individual-level data on differential responses to various types of activity are not yet sufficient in scale, duration or level of annotation to understand the mechanisms of discrete outcomes nor to support personalized recommendations. The Apple Heart & Movement Study was designed to passively collect the dense physiologic data accessible on Apple Watch and iPhone from a large real-world cohort distributed across the US in order to address these knowledge gaps.

Abstract Background The proximal femur is a common site of bone metastasis. The Mirels’ score is a frequently utilized system to identify patients at risk for pathologic fracture and while it has consistently demonstrated strong sensitivity, specificity has been relatively poor. Our group previously developed a Modified Mirels’ scoring system which demonstrated improved ability to predict cases at risk of fracture in this patient population through modification of the Mirels’ location score. The purpose of the present study is to internally validate this newly developed scoring system on an independent patient series. Methods Retrospective review was performed to identify patients who were evaluated for proximal femoral bone lesions. Patients were stratified into one of two groups: 1) those who went on to fracture within 4 months after initial evaluation (Fracture Group) and 2) those who did not fracture within 4 months of initial evaluation (No Fracture Group). Retrospective chart review was performed to assign an Original Mirels’ (OM) Score and Modified Mirels’ (MM) score to each patient at the time of initial evaluation. Descriptive statistics, logistic regression, receiver operating curve, and net benefit analyses were performed to determine the predictability of fractures when utilizing both scoring systems. Results The use of the MM scoring improved fracture prediction over OM scoring for patients observed over a 4 month follow up based on logistic regression. Decision curve analysis showed that there was a net benefit using the MM score over the OM scoring for a full range of fracture threshold probabilities. Fracture prevalence was similar for current internal validation dataset when compared to the dataset of our index study with a comparable reduction in misclassification of fracture prediction when utilizing the modified scoring system versus the original. Conclusions Use of MM scoring was found to improve fracture prediction over OM scoring when tested on an internal validation set of patients with disseminated metastatic lesions to the proximal femur. The improvement in fracture prediction demonstrated in the present study mirrored the results of our index study during which the MM system was developed.

Abstract Background Direct acting antivirals (DAAs) for the Hepatitis C virus (HCV) have shifted the World Health Organisation global strategic focus to the elimination of HCV by 2030. In England, the UK Health Security Agency (UKHSA) led a national ‘patient re-engagement exercise’, using routine surveillance data, which was delivered through the HCV Operational Delivery Networks (ODNs) with support from National Health Service England (NHSE), to help find and support people with a positive HCV PCR test result to access treatment. We report a quantitative evaluation of outcomes of this exercise. Methods Individuals with a recorded positive HCV antibody or PCR result between 1996 and 2017 were identified using UKHSA’s records of HCV laboratory diagnosis. Linkage with established health-care datasets helped to enhance patient identification and minimise attempts to contact deceased or previously treated individuals. From September to November 2018 each ODN was provided with a local list of diagnosed individuals. ODNs were asked to perform further data quality checks through local systems and then write to each individual’s GP to inform them that the individual would be contacted by the ODN to offer confirmatory HCV PCR testing, assessment and treatment unless the GP advised otherwise. Outcomes of interest were receipt of treatment, a negative PCR result, and death. Data were collected in 2022. Results Of 176,555 individuals with a positive HCV laboratory report, 55,329 individuals were included in the exercise following linkage to healthcare datasets and data reconciliation. Participants in the study had a median age of 51 years (IQR: 43, 59), 36,779 (66.5%) were males, 47,668 (86.2%) were diagnosed before 2016 and 11,148 (20.2%) lived in London. Of the study population, 7,442 (13.4%) had evidence of treatment after the re-engagement exercise commenced, 6,435 (11.6%) were reported as PCR negative (96% had no previous treatment records), 4,195 (7.6%) had prescription data indicating treatment before the exercise commenced or were reported to have been treated previously by their ODN, and 2,990 (5.4%) had died. The status of 32,802 (59.3%) people remains unknown. Conclusions A substantial number of those included had treatment recorded after the exercise commenced, however, many more remain unengaged. Evaluation of the exercise highlighted areas that could be streamlined to improve future exercises.