bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cryo-EM and Solid State NMR Together Provide a More Comprehensive Structural Investigation of Protein Fibrils
Authors: Fonda Blake D. , Kato Masato , Li Yang , Murray Dylan T. 
Published: June 2024

AbstractThe Tropomyosin 1 isoform I/C C-terminal domain (Tm1-LC) fibril structure is studied jointly with cryogenic electron microscopy (cryo-EM) and solid state nuclear magnetic resonance (NMR). This study demonstrates the complementary nature of these two structural biology techniques. Chemical shift assignments from solid state NMR are used to determine the secondary structure at the level of individual amino acids, which is faithfully seen in cryo-EM reconstructions. Additionally, solid state NMR demonstrates that the region not observed in the reconstructed cryo-EM density is primarily in a highly mobile random coil conformation rather than adopting multiple rigid conformations. Overall, this study illustrates the benefit of investigations combining cryo-EM and solid state NMR to investigate protein fibril structure.SignificanceThe use of multiple techniques to structurally characterize proteins provides models that accurately describe molecular conformations better than a technique used in isolation. Combination approaches allow for the study of proteins not only as rigid objects, but rather dynamic molecules that “breathe” over time. Cryogenic electron microscopy and solid state nuclear magnetic resonance are used jointly to provide a more detailed model of the same protein fibrils, and each technique provides novel insights.
Global analysis of protein turnover dynamics in single cells
Authors: Sabatier Pierre , Ye Zilu , Lechner Maico , Guzmán Ulises H. , Beusch Christian M. , Izaguirre Fabiana , Seth Anjali , Gritsenko Olga , Rodin Sergey , Grinnemo Karl-Henrik , Olsen Jesper V. 
Published: June 2024

AbstractEven with recent improvements in sample preparation and instrumentation, single-cell proteomics (SCP) analyses mostly measure protein abundances, making the field unidimensional. In this study, we employ a pulsed stable isotope labeling by amino acids in cell culture (SILAC) approach to simultaneously evaluate protein abundance and turnover in single cells (SC-pSILAC). Using state-of-the-art SCP workflow, we demonstrated that two SILAC labels are detectable from ∼4000 proteins in single HeLa cells recapitulating known biology. We investigated drug effects on global and specific protein turnover in single cells and performed a large-scale time-series SC-pSILAC analysis of undirected differentiation of human induced pluripotent stem cells (iPSC) encompassing six sampling times over two months and analyzed >1000 cells. Abundance measurements highlighted cell-specific markers of stem cells and various organ-specific cell types. Protein turnover dynamics highlighted differentiation-specific co-regulation of core members of protein complexes with core histone turnover discriminating dividing and non-dividing cells with potential in stem cell and cancer research. Our study represents the most comprehensive SCP analysis to date, offering new insights into cellular diversity and pioneering functional measurements beyond protein abundance. This method distinguishes SCP from other single-cell omics approaches and enhances its scientific relevance in biological research in a multidimensional manner.
Smart Wristband Monitoring: A Caregiver-Oriented Mobile Application for Tracking Cognitive Decline in Mild Cognitive Impairment Patients
Authors: Ceyhan Barış , Bek Semai , Önal-Süzek Tuğba 
Published: June 2024

AbstractMild Cognitive Impairment (MCI) is the transitional phase between the typical expected memory problems related to age and the more serious decline of dementia. Therefore, monitoring progress from MCI to dementia is critical to slowing down this cognitive deterioration. Research shows that proper nutrition, routine brain, and physical exercise accompanied by proper care slow down the disease significantly. However, most of the patients do not perform these exercises regularly and their vital health data is not monitored properly, leaving patients most of the time with only basic care.In this study, for the first time to our knowledge, we aimed to develop a mobile application that will enable caregivers to continuously monitor the vital health, medication, activity, and location of the patients with MCI with a smart wristband while enabling them caregivers to track the progress of the disease by a machine learning model that tracks MMSE of the patient using speech. Based on our research so far, this caregiver-oriented approach with the ability to track progress of the disease using the convenience of a mobile application is a unique attempt in the field. Patient profile along with collected data is correlated with tracked MMSE scores of the patients to come up with recommendations and findings about the patients. Caregivers are relieved to be notified about critical health data thresholds, progress, and condition of their patients.
WITHDRAWN: ChatGPT-4 as a Board-Certified Surgeon: A Pilot Study
Authors: Roshal Joshua , Silvestri Caitlin , Sathe Tejas , Townsend Courtney , Klimberg V. Suzanne , Perez Alexander 
Published: June 2024

Withdrawal StatementThe authors have withdrawn their manuscript to update the methodology. Therefore, the authors do not wish this work to be cited as a reference for the project. If you have any questions, please contact the corresponding author.
Evaluation of a Novel Large Language Model (LLM) Powered Chatbot for Oral-Boards Scenarios
Authors: Silvestri Caitlin , Roshal Joshua , Shah Meghal , Widmann Warren D. , Townsend Courtney , Brian Riley , L’Huillier Joseph C. , Navarro Sergio M. , Lund Sarah , Sathe Tejas S. 
Published: June 2024

AbstractIntroductionWhile previous studies have demonstrated that generative artificial intelligence (AI) can pass medical licensing exams, AI’s role as an examiner in complex, interactive assessments remains unknown. AI-powered chatbots could serve as educational tools to simulate oral examination dialogues. Here, we present initial validity evidence for an AI-powered chatbot designed for general surgery residents to prepare for the American Board of Surgery (ABS) Certifying Exam (CE).MethodsWe developed a chatbot using GPT-4 to simulate oral board scenarios. Scenarios were completed by general surgery residents from six different institutions. Two experienced surgeons evaluated the chatbot across five domains: inappropriate content, missing content, likelihood of harm, extent of harm, and hallucinations. We measured inter-rater reliability to determine evaluation consistency.ResultsSeventeen residents completed a total of 20 scenarios. Commonly tested topics included small bowel obstruction (30%), diverticulitis (20%), and breast disease (15%). Based on two independent reviewers, evaluation revealed 11 to 25% of chatbot simulations had no errors and an additional 11% to 35% contained errors of minimal clinical significance. Chatbot limitations included incorrect management advice and critical omissions of information.ConclusionsThis study demonstrates the potential of an AI-powered chatbot in enhancing surgical education through oral board simulations. Despite challenges in accuracy and safety, the chatbot offers a novel approach to medical education, underscoring the need for further refinement and standardized evaluation frameworks. Incorporating domain-specific knowledge and expert insights is crucial for improving the efficacy of AI tools in medical education.
Listener effort quantifies clinically meaningful progression of dysarthria in people living with amyotrophic lateral sclerosis
Authors: Bingham Indu Navar , Norel Raquel , Roitberg Esteban G. , Peller Julián , Trevisan Marcos A , Agurto Carla , Shalom Diego E. , Aguirre Felipe , Embon Iair , Taitz Alan , Harris Donna , Wright Amy , Seaver Katie , Sullivan Stacey , Green Jordan R. , Ostrow Lyle W. , Fraenkel Ernest , Berry James D. 
Published: June 2024

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative motor neuron disease that causes progressive muscle weakness. Progressive bulbar dysfunction causes dysarthria and thus social isolation, reducing quality of life. The Everything ALS Speech Study obtained longitudinal clinical information and speech recordings from 292 participants. In a subset of 120 participants, we measured speaking rate (SR) and listener effort (LE), a measure of dysarthria severity rated by speech pathologists from recordings. LE intra- and inter-rater reliability was very high (ICC 0.88 to 0.92). LE correlated with other measures of dysarthria at baseline. LE changed over time in participants with ALS (slope 0.77 pts/month; p<0.001) but not controls (slope 0.005 pts/month; p=0.807). The slope of LE progression was similar in all participants with ALS who had bulbar dysfunction at baseline, regardless of ALS site of onset. LE could be a remotely collected clinically meaningful clinical outcome assessment for ALS clinical trials.
Lung water density is increased in patients at risk of heart failure and is largely independent of conventional CMR measures
Authors: Iyer Nithin R. , Bryant Jennifer A. , Le Thu-Thao , Grenier Justin G. , Thompson Richard B. , Chin Calvin W-L. , Ugander Martin 
Published: June 2024

AbstractAimsNon-invasive methods to quantify pulmonary congestion are lacking in clinical practice. Cardiovascular magnetic resonance (CMR) lung water density (LWD) mapping is accurate, reproducible, and has prognostic value. However, it is not known whether LWD is associated with routinely acquired CMR parameters.Methods and ResultsThis was a prospective, observational cohort including healthy controls and patients at risk of heart failure. Lung water density was measured using CMR with a free-breathing short echo time 3D cartesian gradient-echo sequence with a respiratory navigator at 1.5T. Associations were assessed between LWD, lung water volume (LWV) and cardiac volumes, left ventricular (LV) mass and function, myocardial native T1 and extracellular volume fraction (ECV). In patients at risk for heart failure (n=155), LWD was greater than in healthy controls (n=15) (30.4±5.0 vs 27.2±4.3%, p=0.02). Using receiver operating characteristic analysis, the optimal cut-off for LWD was 27.6% to detect at-risk patients (sensitivity 72%, specificity 73%, positive likelihood ratio 2.7, inverse negative likelihood ratio 2.6). LWD was univariably associated with body mass index (BMI), hypertension, right atrial (RA) area and LV mass (p<0.05 for all). In multivariable linear regression, only BMI remained associated with LWD (R2=0.32, p<0.001). In a separate multivariable analysis including only CMR markers, only RA area remained associated with LWD (R2=0.05, p=0.006).ConclusionLWD is increased in patients at risk for heart failure compared to controls, and is only weakly explained by conventional CMR measures. LWD provides diagnostic information which is largely independent of conventional CMR measures.
The Transition from adolescence to adulthood mental health services for young people with ADHD in Italy
Authors: Roberti E. , Clavenna A. , Basso E. , Bravaccio C. , Riccio M. P. , Pincherle M. , Duca M. , Giordani C. , Scarpellini F. , Campi R. , Giardino M. , Zanetti M. , Tessarollo V. , Costantino I. ,   TransiDEA Group, Bonati M. 
Published: June 2024

AbstractAimsEnsuring a successful transition to Adult Mental Health Services (AMHS) is fundamental for ADHD patients to prevent adverse scenarios in adults (e.g., psychiatric disorders, substance or alcohol abuse). Yet, most European nations do not have appropriate transition guidelines. This study aims to enquire about the current transition paths in Italy and the perceived experiences of the patients and their clinicians.MethodsThe present qualitative, observational study collected 36 interviews with young adults with ADHD who turned 18 between 2017 and 2021. Simultaneously, two questionnaires were filled in by the clinicians (both from pediatric and adult mental health services) who were involved in their transition paths. These tools collected information about the transition process, the services that cared for the young adults, and well-being indicators such as impairment in daily life, employment status, and the presence of sentinel events (e.g., critical stage accesses to the emergency room or hospitalizations). Successful and failed referrals were analyzed.ResultsA referral to an AMHS was attempted for sixteen young adults (8 before age 18 and 8 when turning 18), and 8 patients (22.2% overall) were successfully taken into the care of the AMHS. Twenty patients were not referred since it was deemed unnecessary (N=6) or because of the lack of specialized services or compliance (N=14). At the time of the interview, only nine participants were still under AMHS care. Of eleven individuals with a high need for care (identified by the level of impairment, support needs, or sentinel events), five were not followed by a mental health professional at the time of the interview.ConclusionsFor the majority of ADHD young adults, a transition path was never started or completed. While this is partly due to mild levels of impairment, in many cases it was difficult to find a service that could care for the adult patient. Only 1 out of 4 young adults are successfully transferred to AMHS care. Creating or improving evidence-based transition guidelines should be a priority of the public health system to ensure healthcare for as many patients as possible. The results of this study will converge towards the need for recommendations for the transition of services from adolescence to adulthood for young people with ADHD for Italian clinical practice.
A scoping review of the format, content, effectiveness and acceptability of reproductive life planning tools
Authors: Stewart C , Noh H , Pathak N , Hall JA 
Published: June 2024

AbstractIntroductionA Reproductive Life Plan (RLP) is a set of questions that encourage patients to reflect on their reproductive goals and the actions needed to achieve them. This scoping review of the published and grey literature aims to map the evidence on currently available RLPs.MethodsWe searched four databases (Medline, Embase, PsycINFO and Scopus) and used Google to search the grey literature, the search terms were; “reproductive life plan$” OR “reproductive plans$” OR “pregnancy intention screening”. Data were extracted on target audience, format, content, behaviour change theory, features, effectiveness and acceptability.Results44 published papers and 18 grey literature sources were included. 21 RLPs were discussed in the published papers and 17 in the grey literature. Most RLPs came from the USA. Most RLPs in published papers were asked verbally, while all RLPs in the grey literature were self-completed; there were six digital RLPs. Most ask whether an individual wants children, some then ask about number and timing of children, and contraception. Grey literature RLPs also asked about lifestyle and health.DiscussionThe concept of developing an RLP is acceptable to people of reproductive age and healthcare professionals. There was a lot of consistency in the questions asked, however, there is limited data on effectiveness and only three tools, all digital, incorporated behaviour change theory.ConclusionA digital RLP that builds on the evidence for existing tools and integrates appropriate theory could result in the realisation of the potential that RLPs are theorised to deliver.
Assessing Excess Mortality Patterns in Argentina over the COVID-19 Pandemic (2020-2021): A Comprehensive National and Subnational Analysis
Authors: Pennini Velen , Santoro Adrian , Esteban Santiago , Volij Camila , Rubistein Adolfo 
Published: June 2024

AbstractThe COVID-19 pandemic has dramatically impacted global health metrics, with the World Health Organization (WHO) reporting over 732 million cases and 6.7 million deaths by the end of 2021. Additionally, approximately 14.8 million excess deaths were estimated globally through 2022, significantly surpassing reported COVID-19 deaths. In Argentina, recorded pandemic-related fatalities reached nearly 160,000 from March 2020 to December 2022, underlining the necessity for a detailed examination of excess mortality across national and subnational levels.This study aims to describe excess mortality in Argentina in 2020 and 2021 and its subnational geographic areas, and to identify geographic and temporal disparities across sub-regionsusing publicly available monthly mortality and climate data from Argentina, spanning 2015 to 2021. Excess mortality was assessed using Generalized Additive Models (GAM) to account for long-term and annual trends, monthly climatic variations, and epidemiological reports of Influenza-like Illness (ILI). Data across various geographic regions was analyzed to identify temporal and spatial disparities in mortality.Our analyses revealed significant regional disparities in mortality, identifying a total of 133,612 excess deaths across Argentina during the study period, with notable peaks coinciding with COVID-19 waves. These insights not only contribute to our understanding of the pandemic’s broader effects but also emphasize the critical need for enhanced public health responses informed by mortality data analyses. The development of an open-source, interactive platform further supports this initiative, enabling detailed exploration and informed decision-making to better manage future public health crises.
Costs of home-delivered antiretroviral therapy refills for persons living with HIV: evidence from a pilot randomized controlled trial in KwaZulu-Natal, South Africa
Authors: Tseng Ashley S. , Barnabas Ruanne V. , van Heerden Alastair , Ntinga Xolani , Sahu Maitreyi 
Published: June 2024

AbstractAntiretroviral therapy (ART) is needed across the lifetime to maintain viral suppression for people living with HIV. In South Africa, obstacles to reliable access to ART persist and are magnified in rural areas, where HIV services are also typically costlier to deliver. A recent pilot randomized study (the Deliver Health Study) found that home-delivered ART refills, provided at a low user fee, effectively overcame logistical barriers to access and improved clinical outcomes in rural South Africa. In the present costing study using the payer perspective, we conducted retrospective activity-based micro-costing of home-delivered ART within the Deliver Health Study and when provided at-scale (in a rural setting), and compared to facility-based costs using provincial expenditure data (covering both rural and urban settings). Within the context of the pilot Deliver Health Study which had an average of three deliveries per day for three days a week, home-delivered ART cost (in 2022 USD) $794 in the first year and $714 for subsequent years per client after subtracting client fees, compared with $167 per client in provincial clinic-based care. We estimated that home-delivered ART can reasonably be scaled up to 12 home deliveries per day for five days per week in the rural setting. When delivered at scale, home-delivered ART cost $267 in the first year and $183 for subsequent years per client. Average costs of home delivery further decreased when increasing the duration of refills from three-months to six- and 12-month scripts (from $183 to $177 and $135 per client, respectively). Personnel costs were the largest cost for home-delivered refills while ART drug costs were the largest cost of clinic-based refills. When provided at scale, home-delivered ART in a rural setting not only offers clinical benefits for a hard-to-reach population but is also comparable in cost to the provincial standard of care.
Characterising People who inject drugs, and association with HIV infection: A Situation Analysis in Kampala city, Uganda
Authors: Mudiope Peter , Mathers Bradley , Nangendo Joanita , Samuel Mutyaba , Mutamba Byamah Brian , Alamo Stella , Nanyenya Nicholus , Makumbi Fredrick , Laker-Oketta Miriam , Wanyenze Rhoda 
Published: June 2024

AbstractBackgroundUganda has implemented targeted interventions to address the rising burden of injection drug use, yet barriers persist in reaching persons who inject drugs (PWID). This study describes the characteristics of people who inject drugs, physical and mental health states, and associated risk behaviors, to inform the designing of programs that are tailored to client’s needs and preferences.MethodsA cross-sectional survey was conducted between August and December 2023 at selected hotspots in Kampala, interviewing 499 PWID aged ≥18 years. Data was collected using a semi-structured questionnaire administered by peer educators and Uganda Harm Reduction Network (UHRN) counselors. Measurements included socio-demographics, injecting drug use and sexual risk behaviors, and medical history. HIV serostatus was dtermined by self-report and testing for participants who had no recent history of testing and consented to be tested. Binary logistic regression was used to establish the relationship between HIV infection and risky drug- and sexual behaviors of PWID.ResultsParticipants were predominantly Ugandan (95.2%), male (73.2%), unmarried (55.9%), unemployed (81.8%), with higher levels of education and varying ages. Mental disorders were prevalent, with 48.7% reporting at least one underlying condition, including depression (30.8%) and anxiety (9.6%). Physical health issues were also noted, with reported cases of fever (32.9%), cough (32.5%), malaria (22%) and sexually transmitted infections (STIs) (15%).Regarding drug use patterns, the majority (82.6%) were introduced to drugs by close acquaintances, with 70.9% categorized as people who inject drugs. HIV prevalence among injecting drug users was 3.7%, with higher rates among females (8.4%) and non-Ugandans (16.7%). Being female and experiencing difficulty accessing sterile injection materials were associated with HIV-positive status, highlighting the complex interplay between socio-demographic factors, risk behaviors, and HIV infection among individuals with injecting drug use Disorder in Uganda.ConclusionOur study provides a comprehensive insight into the socio-demographic, mental, physical health, and HIV risk behavoir of PWID in Kampala, Uganda. The findings indicate significant vulnerabilities to injecting drug use, mental disorders, and high-risk behaviors that predispose this population to HIV infection. Despite a low HIV prevalence compared to previous estimates, the interplay between drug use, risky injecting practices, and sexual behaviors suggests an urgent need for targeted interventions to address these intertwined challenges.