Comparing the Performance of Popular Large Language Models on the National Board of Medical Examiners Sample Questions.

INTRODUCTION: Large language models (LLMs) have transformed various domains in medicine, aiding in complex tasks and clinical decision-making, with OpenAI's GPT-4, GPT-3.5, Google's Bard, and Anthropic's Claude among the most widely used. While GPT-4 has demonstrated superior performance in some studies, comprehensive comparisons among these models remain limited. Recognizing the significance of the National Board of Medical Examiners (NBME) exams in assessing the clinical knowledge of medical students, this study aims to compare the accuracy of popular LLMs on NBME clinical subject exam sample questions. METHODS: The questions used in this study were multiple-choice questions obtained from the official NBME website and are publicly available. Questions from the NBME subject exams in medicine, pediatrics, obstetrics and gynecology, clinical neurology, ambulatory care, family medicine, psychiatry, and surgery were used to query each LLM. The responses from GPT-4, GPT-3.5, Claude, and Bard were collected in October 2023. The response by each LLM was compared to the answer provided by the NBME and checked for accuracy. Statistical analysis was performed using one-way analysis of variance (ANOVA). RESULTS: A total of 163 questions were queried by each LLM. GPT-4 scored 163/163 (100%), GPT-3.5 scored 134/163 (82.2%), Bard scored 123/163 (75.5%), and Claude scored 138/163 (84.7%). The total performance of GPT-4 was statistically superior to that of GPT-3.5, Claude, and Bard by 17.8%, 15.3%, and 24.5%, respectively. The total performance of GPT-3.5, Claude, and Bard was not significantly different. GPT-4 significantly outperformed Bard in specific subjects, including medicine, pediatrics, family medicine, and ambulatory care, and GPT-3.5 in ambulatory care and family medicine. Across all LLMs, the surgery exam had the highest average score (18.25/20), while the family medicine exam had the lowest average score (3.75/5).  Conclusion: GPT-4's superior performance on NBME clinical subject exam sample questions underscores its potential in medical education and practice. While LLMs exhibit promise, discernment in their application is crucial, considering occasional inaccuracies. As technological advancements continue, regular reassessments and refinements are imperative to maintain their reliability and relevance in medicine.

Discovery and characterization of noncanonical E2-conjugating enzymes.

E2-conjugating enzymes (E2s) play a central role in the enzymatic cascade that leads to the attachment of ubiquitin to a substrate. This process, termed ubiquitylation, is required to maintain cellular homeostasis and affects almost all cellular process. By interacting with multiple E3 ligases, E2s dictate the ubiquitylation landscape within the cell. Since its discovery, ubiquitylation has been regarded as a posttranslational modification that specifically targets lysine side chains (canonical ubiquitylation). We used Matrix-Assisted Laser Desorption/Ionization-Time Of Flight Mass Spectrometry to identify and characterize a family of E2s that are instead able to conjugate ubiquitin to serine and/or threonine. We used structural modeling and prediction tools to identify the key activity determinants that these E2s use to interact with ubiquitin as well as their substrates. Our results unveil the missing E2s necessary for noncanonical ubiquitylation, underscoring the adaptability and versatility of ubiquitin modifications.

Effects of kinect-based virtual reality training on bone mineral density and fracture risk in postmenopausal women with osteopenia: a randomized controlled trial.

Osteopenia is a condition characterized by low bone mineral density (BMD) that increases fracture risk, particularly among postmenopausal women (PMW). This study aimed to determine the effects of Kinect-based VRT on BMD and fracture risk in PMW with osteopenia. The study was a prospective, two-arm, parallel-design, randomized controlled trial. The study enrolled 52 participants, 26 randomly assigned to each group. In the experimental group, Kinect-based VRT was provided thrice weekly for 24 weeks for 45 min/session. Both groups were instructed to engage in a daily 30-min walk outdoors. The fracture risk assessment tool (FRAX) was used to calculate fracture risk, and dual-energy X-ray absorptiometry was used to measure lumbar spine and femur neck BMD. Both variables were assessed at baseline and 24 weeks afterwards. After 24 weeks of Kinect-based VRT, the experimental group showed significant BMD increases in the right and left femoral necks and lumbar spine (p value < 0.001). In the control group, the BMD at the right and left femoral necks showed fewer significant changes (p value < 0.022 and 0.004, respectively). In the control group, lumbar spine BMD did not change (p = 0.57). The experimental group showed significantly lower FRAX scores for hip fracture prediction (HFP) and hip prediction of major osteoporotic (HPMO) at both femoral necks (p value < 0.001) than the control group (p = 0.05 and p = 0.01, respectively), but no significant change at the left femoral neck for HFP (p = 0.66) or HPMO (p = 0.26). These findings indicate that a Kinect-based VRT intervention resulted in significantly increased BMD and a reduced fracture risk, as predicted by HFP and HPMO measurements. These improvements were more pronounced in the experimental group than in the control group. Thus, Kinect-based VRT may be utilized as an effective intervention to improve BMD and reduce fracture risk in postmenopausal women with osteopenia.

Metal pollution in the topsoil of lands adjacent to Sahiwal Coal Fired Power Plant (SCFPP) in Sahiwal, Pakistan.

Coal fly ash from a coal fired power plant is a significant anthropogenic source of various heavy metals in surrounding soils. In this study, heavy metal contamination in topsoil around Sahiwal coal fired power plant (SCFPP) was investigated. Within distance of 0-10, 11-20, 21-30 and 31-40 km of SCFPP, total 56 soil samples were taken, 14 replicate from each distance along with a background subsurface soil sample beyond 60 km. Soil samples were subjected to heavy metals analysis including Fe, Cu and Pb by Atomic Absorption Spectrophotometer (AAS). Composite samples for each distance were analyzed for Al, As, Ba, Cd, Co, Cr, Mn, Mo, Ni, Se, Sr, Zn by Inductively Coupled Plasma (ICP). Pollution indices of exposed soil including Enrichment Factor (EF), Contamination Factor (CF), Geoaccumulation Index (Igeo), and Pollution Load Index (PLI) were calculated. Ecological risk index ([Formula: see text]) of individual metals and the Potential Ecological Risk Index (PERI) for all metals were determined. Soil samples within 40 km of SCFPP were significantly polluted with Pb (mean 2.81 ppm), Cu (mean 0.93 ppm), and Fe (mean 7.93 ppm) compared to their background values (Pb 0.45, Cu 0.3, and Fe 4.9 ppm). Some individual replicates were highly contaminated where Pb, Fe, and Cu values were as high as 6.10, 35.4 and 2.51 ppm respectively. PLI, Igeo, CF, and EF for metals classified the soil around CFPP as "moderate to high degree of pollution", "uncontaminated to moderately contaminated", "moderate to very high contamination", and "moderate to significant enrichment" respectively with average values for Cu as 2.75, 0.82, 3.09, 4.01; Pb 4.79, 1.56, 6.16, 7.76, and for Fe as 1.20, 0.40, 1.62, 3.35 respectively. Average Ecological Risk Index ([Formula: see text]) of each metal and Potential Ecological Risk Index (PERI) for all metals classified the soils as "low risk soils" in all distances. However, ([Formula: see text]) of Pb at a number of sites in all distances have shown "moderate risk". The linear correlation of physico-chemical parameter (EC, pH, Saturation %) and metals have recorded several differential correlations, however, their collective impact on Pb in 0-10 km, has recorded statistically significant correlation (p-value 0.01). This mix of correlations indicates complex interplay of many factors influencing metal concentrations at different sampling sites. The concentration of As, Cr, Co, Cd, and Zn was found within satisfactory limits and lower than in many parts of the world. Although the topsoil around SCFPP is largely recorded at low risk, for complete assessment of its ecological health, further research considering comprehensive environmental parameters, all important trace metals and variety of input pathways is suggested.

Bicuspid Aortic Valve Disease: Classifications, Treatments, and Emerging Transcatheter Paradigms.

Bicuspid aortic valve (BAV) is a common congenital valvular malformation, which may lead to early aortic valve disease and bicuspid-associated aortopathy. A novel BAV classification system was recently proposed to coincide with transcatheter aortic valve replacement being increasingly considered in younger patients with symptomatic BAV, with good clinical results, yet without randomized trial evidence. Procedural technique, along with clinical outcomes, have considerably improved in BAV patients compared with tricuspid aortic stenosis patients undergoing transcatheter aortic valve replacement. The present review summarizes the novel BAV classification systems and examines contemporary surgical and transcatheter approaches.

Development of Urdu version of Chronic Respiratory Disease Questionnaire Self-Administered Standardized (CRQ-SAS); validity and reliability analysis in COPD patients.

PURPOSE: Chronic Respiratory Disease Questionnaire Self-Administered Standardized (CRQ-SAS) is a valid and reliable tool that evaluates the health-related quality of life among the adult population affected with chronic respiratory disorders (CRDs) and has been translated into many languages as per need. The main objective of this study was to translate the CRQ-SAS into the Urdu language and evaluate its psychometric properties. METHODOLOGY: It was a two-staged study that consisted of translating the original version into Urdu language and then psychometric testing of the translated version. The reliability of the translated questionnaire was assessed by measuring its internal consistency, test-retest reliability, standard error of mean (SEM) & minimal detectable change (MDC). Validity was determined by evaluating its content for content validity, construct (convergent and discriminative) validity, and exploratory factor analysis. Data was analyzed using SPSS v 28 with an alpha level < 0.05 considered to be significant. RESULTS: CRQ-SAS U had an excellent internal consistency (Cronbach's Alpha α = 0.89), test-retest reliability (ICC2,1) = 0.91 of all items, and low SEM = 0.11 and MDC = 0.65. S-CVI was 0.9, with statistically significant difference across the response of COPD patients and healthy subjects, and a high degree of correlation with St Georges Respiratory Questionnaire (r = 0.7-0.9) proving CRQ-SAS U content, discriminant and convergent valid respectively. Exploratory factor analysis identified two factors responsible for 80% of the variance. CONCLUSION: CRQ-SAS U demonstrated optimal psychometric properties which renders it to be used in Urdu speaking populations with COPD.

Association analysis of serotonin transporter gene polymorphism among the South-Indian migraineurs.

Background: Migraine is a multifactorial neurological disorder characterized by frequent moderate to severe intensity headaches. The genetic variations in synaptic and post-receptor signalling proteins have direct effect on the process of serotonergic neurotransmission. Methods: We aimed to investigate the genetic association of serotonin transporter (SERT) 5-hydroxytryptamine transporter-linked promoter region (5-HTTLPR) polymorphism and migraine risk in South-Indian population. A total of 304 subjects with migraine including with aura (MA) and without aura (MO) and 308 controls were included in the present study. The single nucleotide polymorphism (SNP) was detected using polymerase chain reaction (PCR) and confirmed by deoxyribonucleic acid (DNA) sequencing. Results: The genotyping analysis revealed insignificant relationship with migraine subjects when compared with controls (P > 0.05). The minor 'S' allele showed no association with odds ratio (OR) = 1.23 [95% confidence interval (CI): 0.90-1.66], heterozygote with OR = 1.18 (95% CI: 0.82-1.69), and homozygote with OR = 1.51 (95% CI: 0.52-4.35). Conclusion: Further clinical studies are required to validate the results of SERT 5-HTTLPR promoter polymorphism in diverse ethnic descents especially in Asian populations.

Nivolumab-induced Lambert-Eaton myasthenic syndrome: an immune-related adverse event in nonsmall cell lung cancer.

Nivolumab is an anti-programmed cell death protein 1 (anti-PD-1) monoclonal antibody and was the first immune checkpoint inhibitor drug approved for use in advanced non-small cell lung cancer (NSCLC). In this report, we describe a rare case of Lambert-Eaton myasthenic syndrome (LEMS), which developed as a side effect of nivolumab in a patient with metastatic lung squamous cell carcinoma. Our patient, who was previously treated with nivolumab for metastatic squamous cell carcinoma of the lung, appeared with a headache, swollen face, dysarthria, asthenia, xerostomia, and drooping eyelid. Early testing indicated no thymomas or newly developing tumors in whole-body scans, and the blood workup was normal. We came to the conclusion that nivolumab-induced LEMS was the cause of the symptoms after performing nerve conduction investigations ruling out other differentials. We believe our clinical experience of this rare and unexpected adverse event should be shared.

Effects of fasciatherapy versus fascial manipulation on pain, range of motion and function in patients with chronic neck pain.

BACKGROUND: Neck pain is among the common musculoskeletal problem that hinders a person's daily activities. Fascial tightness is a familiar cause of chronic neck pain that is often neglected and can further cause neck disability and a limited range of motion. OBJECTIVE: The purpose was to compare the effects of fascia therapy and fascial manipulation on pain, range of motion and function in patients with chronic neck pain. METHODS: A randomized clinical trial was conducted from February to August 2022 in the Riphah Rehabilitation Centre, Lahore, Pakistan. Fifty-two participants of both genders, aged 18-40 years with chronic neck pain of at least 3-6 months were included. Group A (n = 26) received fascia therapy along with a conventional physical therapy protocol of hot pack, strengthening and stretching, while group B (n = 26) received the fascial manipulation treatment with conventional physical therapy. All the participants were assessed at baseline and after 3 weeks (3 sessions per week). Numeric Pain Rating Scale (NPRS), Neck Disability Index (NDI) and Goniometer (range of motions) were the outcome measures. SPSS 25 was used for the data analysis and normality of the data through the Shaphiro-Wilk test (p > 0.05), and parametric tests were applied. RESULTS: The mean age of group A was 24.82 ± 2.64 years, and group B was 24.17 ± 2.20 years. The independent t-test result showed no significant difference (p ≥ 0.05) in all parameters except in cervical extension and right-side bending (p < 0.05). At the same time, the pair-wise comparison showed significant results (p < 0.05) for all outcome measures in both groups. CONCLUSION: DBM fascia therapy improved cervical extension and side bending (right) more than the fascial manipulation group.It is concluded that DBM fascia therapy shows more improvement as compared to other group. TRIAL REGISTRATION NUMBER: This study was registered at ClinicalTrials.gov ID: NCT05272111 on 09/03/2022.

Microarray needles comprised of arginine-modified chitosan/PVA hydrogel for enhanced antibacterial and wound healing potential of curcumin.

Wound healing is a multifaceted and complex process that includes inflammation, hemostasis, remodeling, and granulation. Failures in any link may cause the healing process to be delayed. As a result, wound healing has always been a main research focus across the entire medical field, posing significant challenges and financial burdens. Hence, the current investigation focused on the design and development of arginine-modified chitosan/PVA hydrogel-based microneedles (MNs) as a curcumin (CUR) delivery system for improved wound healing and antibacterial activity. The substrate possesses exceptional swelling capabilities that allow tissue fluid from the wound to be absorbed, speeding up wound closure. The antibacterial activity of MNs was investigated against S. aureus and E. coli. The results revealed that the developed CUR-loaded MNs had increased antioxidant activity and sustained drug release behavior. Furthermore, after being loaded in the developed MNs, it revealed improved antibacterial activity of CUR. Wound healing potential was assessed by histopathological analysis and wound closure%. The observed results suggest that the CUR-loaded MNs greatly improved wound healing potential via tissue regeneration and collagen deposition, demonstrating the potential of developed MNs patches to be used as an effective carrier for wound healing in healthcare settings.

Effects of micro(nano)plastics on soil nutrient cycling: State of the knowledge.

The ecological impacts of micro(nano)plastics (MNPs) have attracted attention worldwide because of their global occurrence, persistence, and environmental risks. Increasing evidence shows that MNPs can affect soil nutrient cycling, but the latest advances on this topic have not systematically reviewed. Here, we aim to present the state of knowledge about the effects of MNPs on soil nutrient cycling, particularly of C, N, and P. Using the latest data, the present review mainly focuses on three aspects, including (1) the effects and underlying mechanisms of MNPs on soil nutrient cycling, particularly of C, N and P, (2) the factors influencing the effects of MNPs on soil nutrient cycling, and (3) the knowledge gaps and future directions. We conclude that MNPs can alter soil nutrient cycling via mediating soil nutrient availability, soil enzyme activities, functional microbial communities, and their potential ecological functions. Furthermore, the effects of MNPs vary with MNPs characteristics (i.e., polymeric type, size, dosage, and shape), chemical additives, soil physicochemical conditions, and soil biota. Considering the complexity of MNP-soil interactions, multi-scale experiments using environmental relevant MNPs are required to shed light on the effects of MNPs on soil nutrients. By learning how MNPs influence soil nutrients cycles, this review can guide policy and management decisions to safeguard soil health and ensure sustainable agriculture and land use practices.

Immobilization and phytoavailability of antimony (Sb) in contaminated agricultural soils amended with composted manure.

A pot experiment was conducted to assess the Sb phytoavailability and its accumulation in the wheat before and after remediation, using the composted manure of poultry and sheep, and a chemical amendment (limestone). The present study evaluates the effects of amendments on Sb bioavailability in different soils and investigates the relationship between bioaccumulated Sb and its availability in spiked soils using two different single extraction methods. Furthermore, a sequential extraction procedure was used to measure different fractions of Sb in soil, in order to assess the effect of remediation. The results revealed that bioavailability of Sb were highly affected by the three soil amendments on plant height, uptake of Sb by wheat. Poultry compost (Pc) and Sheep compost (Sc) increased the residual fraction of Sb in soils, and decreased the Sb uptake by wheat, enhanced the height, biomass and dry yield of the wheat crop. While the residual fraction of Sb in soils didn't obviously increased by adding Chemical (limestone) in the four soils. It is concluded that uptake of Sb in the soils significantly decreased with the addition of amended materials in the Sb spiked soils, and poultry compost is the most effective. In the lower level of Sb contaminated soils remediated by poultry compost (Pc), the uptake of Sb in wheat decreased 63.1-74.4 %, 68.7-79.0 %, 68.9-76.9 % and 66.3-82.6 % in S1, S2, S3, S4, compared to the contaminated soils without amendments, respectively.

An efficient class of estimators for finite population mean in the presence of non-response under ranked set sampling (RSS).

In this study, we address the problem of estimating the finite population mean when the non-response occurs on the characteristics under study. We propose a class of Rao-regression type estimators when ranked set sampling (RSS) procedure is used to collect the data from non-response group only and from both, the response and non-response groups. The information provided on the auxiliary variable is used at both stages i.e., at designing stage and the estimation stage. Expressions for bias and mean square error of the estimators are obtained up to first order of approximation. A comprehensive simulation study is carried out to observe the performances of the estimators under non-response.

Long-term efficacy, safety, and tolerability of a subcutaneous immunoglobulin 16.5% (cutaquig®) in the treatment of patients with primary immunodeficiencies.

A prospective study and its long-term extension examined whether weekly treatment of patients with primary immunodeficiencies (PIDs) with a 16.5% subcutaneous immunoglobulin (SCIg; cutaquig®) confers acceptable efficacy, safety, and tolerability over a follow-up of up to 238 weeks (>4 years). Seventy-five patients received 4462 infusions during up to 70 weeks of follow-up in the main study and 27 patients received 2777 infusions during up to 168 weeks of follow-up in the extension. In the main study, there were no serious bacterial infections (SBIs), and the annual rate of other infections was 3.3 (95% CI 2.4, 4.5). One SBI was recorded in the extension, for an SBI rate of 0.02 (upper 99% CI 0.19). The annual rate of all infections over the duration of the extension study was 2.2 (95% CI 1.2, 3.9). Only 15.0% (1085) of 7239 infusions were associated with infusion site reactions (ISRs), leaving 85.0% (6153) of infusions without reactions. The majority of ISRs were mild and transient. ISR incidence decreased over time, from 36.9% to 16% during the main study and from 9% to 2.3% during the extension. The incidence of related systemic adverse events was 14.7% in the main study and 7.4% in the extension. In conclusion, this prospective, long-term study with cutaquig showed maintained efficacy and low rates of local and systemic adverse reactions in PID patients over up to 238 weeks of follow-up.

Effects of cervical stabilisation exercises on respiratory strength in chronic neck pain patients with forward head posture.

The objective of this study was to determine the effects of cervical stabilisation exercises on respiratory strength in chronic neck pain patients with forward head posture. The study was conducted from August 2020 to February 2021, at the Jinnah Hospital, Lahore; 44 patients who fulfilled the eligibility criteria were randomly assigned to two groups-experimental group and control group-. Baseline measurement was taken for numeric pain rating scale, neck disability index, craniovertebral angle, single breath count, and spirometry and all the measurements were retaken at the completion of the fourth week. Results were not significant (p>0.05) before the treatment in both groups but post-intervention results revealed significant differences in both the groups (p<0.05), with the experimental group showing more improvement. Four weeks of cervical stabilisation with isometric exercises is more effective in the management of pain, forward head posture, neck disability and respiratory strength as compared with the four weeks of isometric exercises programme alone.

Effects of decompression on pain, range of motion and function in patients with acute vs chronic lumbar radiculopathy.

The purpose of this study was to determine the effects of manual lumbar decompression on pain, range of motion, and function in patients with acute vs chronic lumbar radiculopathy. Thirty patients fulfilling the eligibility criteria at Tehsil Headquarter Civil Hospital Daska were randomly placed into three groups: acute group (n=10), chronic group (n=10), and control group (n=10). Mean age of the participants was 33.3±8.5 years and the mean body mass index was 25.0±4.4. There were 12 males and 21 female participants. Group A and Group B were 18 treated with decompression, lumbar mobilisation, hot packs, TENS and exercise therapy, while the patients in Group C were treated with lumbar mobilisation, hot packs and exercise therapy. Total duration of the treatment was four weeks at three sessions per week and the outcomes were measured at baseline and at the completion of four-week treatment with Visual Analogue Scale, Modified Oswestry Disability index, Straight Leg Raise, and Inclinometer. Data was analysed by using SPSS version 25. One Way ANOVA and Kruskal-Wallis Test were used to compare the means across the groups. It was concluded that manual lumbar decompression decreases pain, and increases range of motion and function in Group A (acute) as compared to Group B (chronic) and Group C (control).

Teaching strategies for rehabilitation curriculum: Coping with the Covid-19 situation.

The novel corona virus pandemic culminated in a global emergency shutting down educational institutions with recommendations of distant learning. Developing countries like Pakistan faced challenges in terms of keeping the education stream running. The current narrative review was planned to discuss the teaching strategies adopted by various institutes for coping with the situation created by the coronavirus disease-2019. Literature search was done using search engines and databases with key words 'Academics', 'Coping strategies', 'Covid-19', 'Online learning', 'Rehabilitation curriculum' and their combinations. As a result, 37 articles were analysed for education involving conformation of curricula to social distancing protocol, and use of video-conferencing software, practical rehabilitation curriculum delivery, and evaluation methods. Developing countries, like Pakistan, should upgrade and revise their rehabilitation curriculum at theoretical and practical levels and try to convert the adversity of the pandemic into an opportunity to develop standardised e-learning programmes and compatible software.

Biomonitoring of mercury in water, sediments, and fish (brown and rainbow trout) from remote alpine lakes located in the Himalayas, Pakistan.

Mercury (Hg) contamination of aquatic ecological units and subsequent bioaccumulation are major environmental problems of international scope. Moreover, the biogeochemistry of Hg in the remote alpine lakes aquatic ecosystem in the Himalayas remains largely unexplored. The current study investigated Hg concentrations in different environmental compartments such as water, fish, and sediments in the remote alpine lakes (RALs) including Glacial-fed Lake, Ice melting-fed Lake, and Rain-fed Lake in northern areas of Pakistan. The mean concentration of Hg in Rain-fed Lake water was (1.07 µg L-1), Ice melting-fed Lake (1.16 µg L-1), and Glacial-fed Lake (1.95 µg L-1). For fish muscle tissues, mean concentration of Hg was 1.02 mg kg-1 in the Rain-fed Lake, and 1.2 mg kg-1 for the Ice melting-fed Lake, and 1.51 mg kg-1 in the Glacial-fed Lake. Meanwhile, 0.27 mg kg-1 was observed for sediments in the Rain-fed Lake, 0.33 mg kg-1 for the Ice melting-fed Lake, and 0.38 mg kg-1 for the Glacial-fed Lake, respectively. Chronic daily intake (CDI) and potential health quotient (PHQ) for water showed high health risk in Glacial-fed Lake and low in Rain-fed Lake (PHQ < 1). The target hazard quotient (THQ) values for both the Brown and Rainbow trout in all the studied lakes water were less than 1, indicating no health risk. Furthermore, the Hg level showed high level of contamination in the sediments of all the studied lakes (190 ≤ RI < 380). Overall, Glacial-fed Lake water was more polluted with Hg, as compared to Rain-fed Lake and Ice melting-fed Lake. In the light of the abovementioned results, further research work is urgently needed to shed light on the biological and geochemical monitoring of Hg in arid high-altitude ecosystems along with source identification, mercury speciation, and other potential pollutants.