bluuebunny/crossref_metadata_2025 huggingface dataset:
Short-term responses of meat ewes facing an acute nutritional challenge in early-mid lactation
Authors: González-García Eliel , Gindri Marcelo , Durand Christian , Lafon Noëllie , Douls Sébastien , Bonafe Gaëtan , Coulon Valentin , Hazard Dominique , Bonnal Laurent , Tesnière Anne , Llach Irene , Parisot Sara , Puillet Laurence
Published: December 2023

Simulating a consequence of a climate change event on feed availability, responses of Mediterranean meat ewes facing an acute undernutritional challenge (CHA; i.e., fed only low nutritional value cereal straw) were evaluated at a sensitive physiological stage (i.e., early suckling). Forty Romane ewes were chosen at early-mid pregnancy (around 2 mo) according to parity (20 primiparous, PRIM; 20 multiparous, MULT); feed efficiency genetic line of their sires (residual feed intake [RFI]; efficient, RFI−, n = 10 per parity; inefficient, RFI+, n = 10 per parity); litter size (i.e., bearing twins, diagnosed by ultrasonography); body weight (BW, kg) and body condition score (BCS) (initial BW and BCS [mean ± SD]: 51.6 ± 7.41 kg; 2.5 ± 0.20, respectively; representing flock’ averages per parity). Effects on dry matter intake (DMI), ewes’ BW and BCS, subcutaneous dorsal fat thickness (DFT), energy metabolism (plasma non-esterified fatty acids [NEFA], β-hydroxybutyrate (β-OHB), glucose, urea, triiodothyronine [T3]), and lambs’ growth (BW and average daily gain [ADG]; g/d) were examined before, during and after CHA. Individuals’ profiles of the response-recovery to CHA were described using a piecewise mixed-effects model. The fixed effect of parity and genetic line and the random effect of individual (ewe) were considered. A linear mixed-effects model was fitted to explore the effects on lambs’ growth. The 2-d straw-only CHA had significant effects on most of the recorded parameters. Meaningful drops and recoveries were observed on ewes’ DMI, BW, and DFT with effect on postchallenge levels. BW, BCS, DFT, or DMI were also affected by parity (MULT > PRIM) but not by genetic line. Plasma NEFA, β-OHB, glucose, urea, and T3 responded well to CHA with drops in T3, urea, and glucose levels, whereas NEFA and β-OHB significantly increased after CHA. MULT ewes presented sharper β-OHB recovery from CHA than PRIM (P ≤ 0.05). With this study, we provide tangible and necessary data for an emerging field of research. Our results give new insights into how such a short and abrupt CHA affects some key zootechnical and physiological parameters, and to what extent the impacts of CHA and the ewes’ response-recovery are influenced. It also revealed potential between-individual differences in the adaptive capacities of ewes, which require further exploration.
Caveolin‐1 promotes mitochondrial health and limits mitochondrial ROS through ROCK/AMPK regulation of basal mitophagic flux
Authors: Timmins Logan R. , Ortiz‐Silva Milene , Joshi Bharat , Li Y. Lydia , Dickson Fiona H. , Wong Timothy H. , Vandevoorde Kurt R. , Nabi Ivan R.
Published: December 2023

Caveolin‐1 (CAV1), the main structural component of caveolae, is phosphorylated at tyrosine‐14 (pCAV1), regulates signal transduction, mechanotransduction, and mitochondrial function, and plays contrasting roles in cancer progression. We report that CRISPR/Cas9 knockout (KO) of CAV1 increases mitochondrial oxidative phosphorylation, increases mitochondrial potential, and reduces ROS in MDA‐MB‐231 triple‐negative breast cancer cells. Supporting a role for pCAV1, these effects are reversed upon expression of CAV1 phosphomimetic CAV1 Y14D but not non‐phosphorylatable CAV1 Y14F. pCAV1 is a known effector of Rho‐associated kinase (ROCK) signaling and ROCK1/2 signaling mediates CAV1 promotion of increased mitochondrial potential and decreased ROS production in MDA‐MB‐231 cells. CAV1/ROCK control of mitochondrial potential and ROS is caveolae‐independent as similar results were observed in PC3 prostate cancer cells lacking caveolae. Increased mitochondrial health and reduced ROS in CAV1 KO MDA‐MB‐231 cells were reversed by knockdown of the autophagy protein ATG5, mitophagy regulator PINK1 or the mitochondrial fission protein Drp1 and therefore due to mitophagy. Use of the mitoKeima mitophagy probe confirmed that CAV1 signaling through ROCK inhibited basal mitophagic flux. Activation of AMPK, a major mitochondrial homeostasis protein inhibited by ROCK, is inhibited by CAV1‐ROCK signaling and mediates the increased mitochondrial potential, decreased ROS, and decreased basal mitophagy flux observed in wild‐type MDA‐MB‐231 cells. CAV1 regulation of mitochondrial health and ROS in cancer cells therefore occurs via ROCK‐dependent inhibition of AMPK. This study therefore links pCAV1 signaling activity at the plasma membrane with its regulation of mitochondrial activity and cancer cell metabolism through control of mitophagy.
Estrogen contributes to sex differences in M2a macrophages during multi‐walled carbon nanotube‐induced respiratory inflammation
Authors: Ray Jessica L. , Postma Britten , Kendall Rebekah L. , Ngo Minh Dao , Foo Cheng Xiang , Saunders Brett , Ronacher Katharina , Gowdy Kymberly M. , Holian Andrij
Published: December 2023

Lung diseases characterized by type 2 inflammation are reported to occur with a female bias in prevalence/severity in both humans and mice. This includes previous work examining multi‐walled carbon nanotube (MWCNT)‐induced eosinophilic inflammation, in which a more exaggerated M2a phenotype was observed in female alveolar macrophages (AMs) compared to males. The mechanisms responsible for this sex difference in AM phenotype are still unclear, but estrogen receptor (ER) signaling is a likely contributor. Accordingly, male AMs downregulated ERα expression after MWCNT exposure while female AMs did not. Thus, ER antagonist Fulvestrant was administered prior to MWCNT instillation. In females, Fulvestrant significantly attenuated MWCNT‐induced M2a gene expression and eosinophilia without affecting IL‐33. In males, Fulvestrant did not affect eosinophil recruitment but reduced IL‐33 and M2a genes compared to controls. Regulation of cholesterol efflux and oxysterol synthesis is a potential mechanism through which estrogen promotes the M2a phenotype. Levels of oxysterols 25‐OHC and 7α,25‐OHC were higher in the airways of MWCNT‐exposed males compared to MWCNT‐females, which corresponds with the lower IL‐1β production and greater macrophage recruitment previously observed in males. Sex‐based changes in cholesterol efflux transporters Abca1 and Abcg1 were also observed after MWCNT exposure with or without Fulvestrant. In vitro culture with estrogen decreased cellular cholesterol and increased the M2a response in female AMs, but did not affect cholesterol content in male AMs and reduced M2a polarization. These results reveal the modulation of (oxy)sterols as a potential mechanism through which estrogen signaling may regulate AM phenotype resulting in sex differences in downstream respiratory inflammation.
Biochemical characterization of the Drosophila insulin receptor kinase and longevity‐associated mutants
Authors: Krishnan Harini , Ahmed Sultan , Hubbard Stevan R. , Miller W. Todd
Published: December 2023

Drosophila melanogaster (fruit fly) insulin receptor (D‐IR) is highly homologous to the human counterpart. Like the human pathway, D‐IR responds to numerous insulin‐like peptides to activate cellular signals that regulate growth, development, and lipid metabolism in fruit flies. Allelic mutations in the D‐IR kinase domain elevate life expectancy in fruit flies. We developed a robust heterologous expression system to express and purify wild‐type and longevity‐associated mutant D‐IR kinase domains to investigate enzyme kinetics and substrate specificities. D‐IR exhibits remarkable similarities to the human insulin receptor kinase domain but diverges in substrate preferences. We show that longevity‐associated mutations reduce D‐IR catalytic activity. Deletion of the unique kinase insert domain portion or mutations proximal to activating tyrosines do not influence kinase activity, suggesting their potential role in substrate recruitment and downstream signaling. Through biochemical investigations, this study enhances our comprehension of D‐IR's role in Drosophila physiology, complementing genetic studies and expanding our knowledge on the catalytic functions of this conserved signaling pathway.
Closing the Academic–Practice Gap With Enhanced Preceptor Training
Authors: Kosanke Heidi , Bednarek Salina , Schaeffer Robin , Hallberg Colleen
Published: December 2023

A successful pilot program served as a model for how educators in healthcare organizations can reduce the academic–practice gap by supporting preceptors. Preceptors received enhanced training using self-paced online modules and an asynchronous online problem-based learning. Statistically significant increases in self-efficacy and satisfaction with training were reported. Preceptor training included strategies for teaching prioritization, communication, and clinical judgment. Preceptors experienced sustained resilience, increased awareness of well-being, and more engagement in the precepting role.
SINGLE CELL DISSECTION OF DEVELOPMENTAL ORIGINS AND TRANSCRIPTIONAL HETEROGENEITY IN B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: Iacobucci Ilaria , Zeng Andy G.X. , Gao Qingsong , Garcia-Prat Laura , Baviskar Pradyumna , Shah Sayyam , Murison Alex , Voisin Veronique , Chan-Seng-Yue Michelle , Cheng Cheng , Qu Chunxu , Bailey Colin , Lear Matthew , Witkowski Matthew T. , Zhou Xin , Peraza Airen Zaldivar , Gangwani Karishma , Advani Anjali S. , Luger Selina M. , Litzow Mark R. , Rowe Jacob M , Paietta Elisabeth M. , Stock Wendy , Dick John E. , Mullighan Charles G
Published: December 2023

Sequencing of bulk tumor populations has improved genetic classification and risk assessment of B-ALL, but does not directly examine intratumor heterogeneity or infer leukemia cellular origins. We profiled 89 B-ALL samples by single-cell RNA-seq (scRNA-seq) and compared them to a reference map of normal human B-cell development established using both functional and molecular assays. Intra-sample heterogeneity was driven by cell cycle, metabolism, differentiation, and inflammation transcriptional programs. By inference of B lineage developmental state composition, nearly all samples possessed a high abundance of pro-B cells, with variation between samples mainly driven by sub-populations. However,ZNF384-r andDUX4-r B-ALL showed composition enrichment of hematopoietic stem cells,BCR::ABL1andKMT2A-r ALL of Early Lymphoid progenitors,MEF2D-r andTCF3::PBX1of Pre-B cells. Enrichment of Early Lymphoid progenitors correlated with high-risk clinical features. Understanding variation in transcriptional programs and developmental states of B-ALL by scRNA-seq refines existing clinical and genomic classifications and improves prediction of treatment outcome.
Expanding the toolbox: Novel class IIb microcins show activity against Gram-negative ESKAPE and plant pathogens
Authors: Mortzfeld Benedikt M. , Bhattarai Shakti K. , Bucci Vanni
Published: December 2023

Interspecies interactions involving direct competition via bacteriocin production play a vital role in shaping ecological dynamics within microbial ecosystems. For instance, the ribosomally-produced siderophore bacteriocins, known as class IIb microcins, affect the colonization of host-associated pathogenicEnterobacteriaceaespecies. Notably, to date, only five of these antimicrobials have been identified, all derived from specificEscherichia coliandKlebsiella pneumoniaestrains. We hypothesized that class IIb microcin production extends beyond these specific compounds and organisms. With a customized informatics-driven approach, screening bacterial genomes in public databases with BLAST and manual curation, we have discovered twelve previously unknown class IIb microcins in seven additionalEnterobacteriaceaespecies, encompassing phytopathogens and environmental isolates. We introduce three novel clades of microcins (MccW, MccX, and MccZ), while also identifying eight new variants of the five known class IIb microcins. To validate their antimicrobial potential, we heterologously expressed these microcins inE. coliand demonstrated efficacy against a variety of bacterial isolates, including plant pathogens from the generaBrenneria, Gibbsiella, and Rahnella. Two newly discovered microcins exhibit activity against Gram-negative ESKAPE pathogens, i.e.Acinetobacter baumanniiorPseudomonas aeruginosa, providing the first evidence that class IIb microcins can target bacteria outside of theEnterobacteriaceaefamily. This study underscores that class IIb microcin genes are more prevalent in the microbial world than previously recognized and that synthetic hybrid microcins can be a viable tool to target clinically relevant drug-resistant pathogens. Our findings hold significant promise for the development of innovative engineered live biotherapeutic products tailored to combat these resilient bacteria.
Feedback Processing as it Relates to Suicidal Ideation and Behavior Using a Time-Frequency Approach
Authors: Pavuluri Asha , Ellis Jessica , Vivino Anthony , Butler Devin , Arenson Melanie , Joiner Thomas , Schmidt Brad , Bernat Edward
Published: December 2023

Background

Suicidal ideation (SI) and suicidal behavior (SB) may have different etiological pathways, particularly related to feedback processing. Identifying ERP components related to these suicide states may help researchers localize and understand these differences.Objective.Our primary purpose was to utilize time-frequency decomposition techniques to assess neurophysiological correlates of SI and SB during positive and negative feedback processing.

Methods

271 subjects (55.7% female; mean age=35.75, SD=16.07; 30.6% veterans) completed a questionnaire battery and a multi-task protocol, including a gambling feedback task (Gehring & Willoughby, 2002), while electroencephalography (EEG) was collected using a 96-channel EEG system. Exploratory factor analysis (EFA) was conducted across 20 self-report suicide items selected to index SI and SB from several suicide-relevant questionnaires. EFA results produced 2 factors, corresponding to SI and SB. Time-frequency principal component analyses produced measures across all frequency bands (i.e., delta-FN/P3, delta-SW, theta-FN, alpha, beta-1, beta-2, and gamma).

Results

Excepting alpha amplitude, all measured frequencies were related to SB, and not SI (across loss and gain, with some loss-gain differences). Alpha, uniquely, showed a relationship to SI and not to SB (across loss and gain, no loss-gain differences). Robust regressions confirmed that the delta, theta, and high-frequency (HF; beta-1, beta-2, and gamma as combined HF loss, gain, and loss-gain difference factors) measures were each independently related to SB.

Discussion

Broadly, the results indicate that individuals with SB showed heightened neurophysiological response across multiple ERP components (except alpha) to gambling feedback, with significantly greater increases to loss stimuli relative to gain stimuli.

General Scientific Summary

This study, using time-frequency EEG/ERP measures from a gambling feedback task, supports the theoretical framework that suicidal behavior and suicidal ideation can be indexed separately. Generally, stronger reactivity to all feedback (i.e., loss and gain feedback during a gambling task) is seen in those with suicidal behavior and not in those with suicidal ideation, but with a small separate effect related to suicidal ideation.
Characterizing mobility patterns and malaria risk factors in semi-nomadic populations of Northern Kenya
Authors: Meredith Hannah R. , Wesolowski Amy , Okoth Dennis , Maraga Linda , Ambani George , Chepkwony Tabitha , Abel Lucy , Kipkoech Joseph , Lokoel Gilchrist , Esimit Daniel , Lokemer Samuel , Maragia James , O’Meara Wendy Prudhomme , Obala Andrew A.
Published: December 2023

While many studies have characterized mobility patterns and disease dynamics of individuals from settled populations, few have focused on more mobile populations. Highly mobile groups are often at higher disease risk due to their regular movement that may increase the variability of their environments, reduce their access to health care, and limit the number of intervention strategies suitable for their lifestyles. Quantifying the movements and their associated disease risks will be key to developing intervention strategies more suitable for mobile populations. Here, we worked with four semi-nomadic communities in Central Turkana, Kenya to 1) characterize mobility patterns of travelers from semi-nomadic communities and 2) test the hypothesis that semi-nomadic individuals are at greater risk of exposure to malaria during seasonal migrations than when staying at their semi-permanent settlements. From March-October, 2021, we conducted a study in semi-nomadic households (n=250) where some members traveled with their herd while others remained at the semi-permanent settlement. Participants provided medical and travel histories, demographics, and a dried blood spot for malaria testing before and after the travel period. Further, a subset of travelers was given GPS loggers to document their routes. Four travel patterns emerged from the logger data, Long Term, Transient, Day trip, and Static, with only Long Term and Transient trips being associated with malaria cases detected in individuals who carried GPS devices. After completing their trips, travelers had a higher prevalence of malaria than those who remained at the household (9.2% vs 4.4%), regardless of gender, age group, and catchment area. These findings highlight the need to develop intervention strategies amenable to mobile lifestyles that can ultimately help prevent the transmission of malaria.
Correlation of Social Determinants of Health and Chronic Nonspecific Low Back Pain; A Brief Report
Authors: Ebrahimi Alireza , Rhee Hyunjoon , Taseh Atta , Rhim Hye Chang , Ashkani-Esfahani Soheil
Published: December 2023

Background

Low back pain (LBP) ranks as one of the top contributors to disability-adjusted life years worldwide. Social determinants of health (SDoH) encompass a range of factors that play a pivotal role in shaping healthcare outcomes. We aimed to examine the differences in SDoH between patients with acute and chronic non-specific low back pain (NSLBP).

Methods

This study was a retrospective case-control study on patients who were admitted to four tertiary hospitals affiliated with Massachusetts General Hospital. Relevant ICD-9 and ICD-10 codes were used to detect patients with LBP. Patients with specific diagnoses such as degenerative joint diseases or primary or secondary bone tumors were excluded. SDoH variables along with the Social Vulnerability Index (SVI) and Area Deprivation Index (ADI) were collected. Wilcoxon rank sum and Chi-square tests were performed to assess the difference between the cohorts.

Results

Of 2,278 patients who were labeled as chronic LBP, 17 were included. The number of female patients was significantly higher (P < 0.05). Furthermore, we didn’t observe any considerable difference between these two groups of patients regarding the SDoH, SVI, and ADI values.

Conclusion

The prevalence of chronic NSLBP in tertiary healthcare centers might be lower. SDoH, ADI, and SVI seem not to contribute to the chronicity of NSCLBP. Future research is needed to further our understanding of the risk factors associated with NSLBP, particularly in different healthcare settings.

Significance/Implications

Although, SDoH variables are mentioned as risk factors, considering the clinical setting when applying the knowledge seem to play an important role.
The cumulative impact of clinical risk on brain networks and associations with executive function impairments in adolescents with congenital heart disease
Authors: Ehrler Melanie , Speckert Anna , Kretschmar Oliver , O’Gorman Ruth Tuura , Latal Beatrice , Jakab Andras
Published: December 2023

Congenital heart disease (CHD) is known to negatively affect brain development. Individual clinical factors have been identified to contribute to this detrimental effect, however, the cumulative effect of these factors on brain development and neurodevelopmental outcomes are not fully understood. Our study utilized structural brain connectomics as an indicator of brain development to investigate the potential combined impact of clinical risk factors and family-environmental factors in adolescents with CHD.

We developed a cumulative clinical risk (CCR) score by summing up binary risk factors (neonatal, cardiac, neurologic) based on clinically relevant thresholds and further investigated the role of family-environmental factors (parental education, parental mental health, and family function). Brain development in 53 adolescents with CHD who underwent infant open-heart surgery, and 75 healthy controls was studied by diffusion MRI connectomic analysis and neuropsychological assessments. The CCR score explains a great variability of the structural brain connectome. A higher CCR score was associated with lower network segregation, edge strength, and executive functioning. Edge strength was particularly reduced in an inter-frontal and fronto-parietal-thalamic network. There was no association with family-environmental factors. Poorer executive functioning was associated with lower network integration and segregation.

Our results provide evidence for persisting alterations of network connectivity in adolescents with CHD – particularly in those patients who face a cumulative exposure to multiple clinical risk over time. Quantifying the cumulative load of risk early in life, may help to better predict trajectories of brain development in order to identify and support the most vulnerable patients as early as possible.
Focal Usual Interstitial Pneumonia-like Fibrosis is a Core Prognostic Factor in Progressive Pulmonary Fibrosis
Authors: Tsushima Yukio , Okoshi Ethan N. , Ishijima Sousuke , Bychkov Andrey , Lami Kris , Morimoto Shimpei , Yamano Yasuhiko , Kataoka Kensuke , Johkoh Takeshi , Kondoh Yasuhiro , Fukuoka Junya
Published: December 2023

Progressive pulmonary fibrosis (PPF) is a newly recognized clinical phenotype of interstitial lung diseases in the 2022 interstitial pulmonary fibrosis (IPF) guidelines. This category is based entirely on clinical and radiological factors, and the background histopathology is unknown. Our objective was to investigate the histopathological characteristics of PPF and to examine the correlation between usual interstitial pneumonia (UIP) and prognosis in this new disease type. We hypothesized that the presence of UIP like fibrosis predicts patients’ survival in PPF cases.

We selected 201 cases fulfilling the clinical criteria of PPF from case archives. Cases diagnosed as IPF by a multidisciplinary team were excluded. Whole slide images were evaluated by three pathologists who were blind to clinical and radiological data. We measured areas of UIP-like fibrosis and calculated what percentage of the total lesion area they occupied.

The presence of focal UIP-like fibrosis amounting to 10% or more of the lesion area was seen in 148 (73.6%), 168 (83.6%), and 165 (82.1%) cases for each pathologist respectively. The agreement of the recognition of UIP-like fibrosis in PPF cases was above κ = 0.6 between all pairs. Survival analysis showed that the presence of focal UIP-like fibrosis correlated with worsened survival under all parameters tested (p < 0.001).

The presence of UIP-like fibrosis is a core pathological feature of clinical PPF and its presence within diseased areas is associated with poorer prognosis. This study highlights the importance of considering the presence of focal UIP like fibrosis in the evaluation and management of PPF.
An amplicon-based Illumina and nanopore sequencing workflow for Chikungunya virus West Africa genotype
Authors: Dieng Idrissa , Ndiaye Mignane , Kane Mouhamed , Balde Diamilatou , Mbanne Maimouna , Diop Seynabou Mbaye Ba Souna , Sankhe Safietou , Dia Moussa , Dieng Madeleine , Doukanda Serge Freddy Moukaha , Faye Ousmane , Sall Amadou Alpha , Dia Ndongo , Fall Gamou , Faye Oumar , Diagne Moussa Moise
Published: December 2023

The Chikungunya virus, a global arbovirus, is currently causing a major outbreak in the Western African region, with the highest cases reported in Senegal and Burkina Faso. Recent molecular evolution analyses reveal that the strain responsible for the epidemic belongs to the West African genotype, with new mutations potentially impacting viral replication, antigenicity, and host adaptation. Real-time genomic monitoring is needed to track the virus’s spread in new regions. A scalable West African genotype amplicon-based Whole Genome Sequencing for multiple Next Generation Sequencing platforms has been developed to support genomic investigations and identify epidemiological links during the virus’s ongoing spread. This technology will help identify potential threats and support real-time genomic investigations in the ongoing spread of the virus.
The Association between Helicobacter pylori Infection and Triglyceride-Glucose (TyG) Index in US Adults: a restrospective cross-sectional study
Authors: Fu Wei , zhao Junlong , Chen GuoBin , Lyu Linya , Ding Yao , Xu Liang-Bi
Published: December 2023

Background

The Triglyceride-glucose (TyG) index is an emerging marker for insulin resistance and metabolic syndrome. Helicobacter pylori, a bacterium associated with gastrointestinal diseases, may also influence metabolic risk profiles. This study aimed to investigate the relationship between the TyG index and Helicobacter pylori infection among a representative sample of adults.

Methods

A total of 9965 participants from the NHANES 1999-2000 cycle were involved from March 1, 1999, to December 1, 2000.A cross-sectional analysis was conducted on 3797 participants. The baseline characteristics according to the quartile of the TyG index were evaluated.Multivariate binary logistic regression models were constructed to analyze the independent effects of the TyG index on Helicobacter pylori infection. A two-piecewise binary logistic regression model was used to explore the non-linear relationship between the TyG index and Helicobacter pylori, with an inflection point identified. Subgroup analyses were performed to assess the trends of effect sizes across different variables including age, sex, glucose levels, body mass index (BMI), and chronic kidney disease (CKD).

Results

Multivariate analysis indicated a linear relationship between the TyG index and Helicobacter pylori infection, suggesting differential influence of the TyG index on Helicobacter pylori infection. Subgroup analysis demonstrated significant interactions only for a few variables, with all p-values for interaction below 0.05.

Conclusions

The study suggests a linear association between the TyG index and Helicobacter pylori infection.These findings have implications for understanding the metabolic influences on Helicobacter pylori infection and may guide targeted interventions for at-risk populations.
Longitudinal Assessment of Mental Health in Antarctica Expeditioners
Authors: Nagendran S , Ahmad Aftab , Nath Ravindra , Nangalia Shalini , Maurya Chandrakant , Dutt D Ganga , Kanojia Aakash
Published: December 2023

Antarc’ca is known for its harsh climate and long, dark winters. Scien’sts and support staff posted in various base sta’ons in Antarc’ca face unique challenges, which include social isola’on, lack of communica’on from the outside world and prolonged working hours. This may lead to changes in their mental health status during their pos’ng. A longitudinal observa’onal study is planned to evaluate the mental health status and changes in it among the Antarc’c expedi’oners. A detailed protocol is presented in this paper.
Analysis of bacteria, inflammation, and exudation in epidermal suction blister wounds reveals dynamic changes during wound healing
Authors: Lundgren Sigrid , Petruk Ganna , Wallblom Karl , Cardoso José FP , Strömdahl Ann-Charlotte , Forsberg Fredrik , Luo Congyu , Nilson Bo , Hartman Erik , Fisher Jane , Puthia Manoj , Saleh Karim , Schmidtchen Artur
Published: December 2023

The skin microbiome undergoes dynamic changes during different phases of wound healing, however the role of bacteria in the wound healing process remains poorly described. In this study, we aimed to determine how wound bacteria develop over time in epidermal wounds, and how they interact with inflammatory processes during wound healing. To this end, we analyzed wound fluid and swab samples collected from epidermal suction blister wounds in healthy volunteers. We found that bacterial numbers, measured in swabs and dressing fluid, increased rapidly after wounding and stabilized by day 8. The composition of bacterial species identified by MALDI-TOF mass spectrometry differed between wounds, but generally consisted primarily of commensal bacteria and remained largely stable over time. Inflammation and neutrophil activity, measured by quantification of cytokines and neutrophil proteins in dressing fluid, peaked on day 5. Exudation, measured by quantification of protein content in dressings, also peaked at this time and strongly correlated with cytokine and neutrophil protein levels. Inflammation, neutrophil activity, and exudation were not correlated with bacterial counts at any time, indicating that in normally healing wounds, these processes are primarily driven by the host and are independent of colonizing bacteria. Our analysis provides a comprehensive understanding of epidermal wound healing dynamics in the host and the role of the microbiome in healthy wound healing.
Investigating the Nature of Open Science Practices Across Complementary, Alternative, and Integrative Medicine Journals: An Audit
Authors: Ng Jeremy Y. , Lin Brenda , Parikh Tisha , Cramer Holger , Moher David
Published: December 2023

Background

Open science practices are implemented across many scientific fields to improve transparency and reproducibility in research. Complementary, alternative, and integrative medicine (CAIM) is a growing field that may benefit from adoption of open science practices. The efficacy and safety of CAIM practices, a popular concern with the field, can be validated or refuted through transparent and reliable research. Investigating open science practices across CAIM journals by using the Transparency and Openness Promotion (TOP) guidelines can potentially promote open science practices across CAIM journals. The purpose of this study is to conduct an audit that compares and ranks open science practices adopted by CAIM journals against TOP guidelines laid out by the Center for Open Science (COS).

Methods

CAIM-specific journals with titles containing the words “complementary”, “alternative” and/or “integrative” were included in this audit. Each of the eight TOP criteria were used to extract open science practices from each of the CAIM journals. Data was summarized by the TOP guideline and ranked using the TOP Factor to identify commonalities and differences in practices across the included journals.

Results

A total of 19 CAIM journals were included in this audit. Across all journals, the mean TOP Factor was 2.95 with a median score of 2. The findings of this study reveal high variability among the open science practices required by journals in this field. Four journals (21%) had a final TOP score of 0, while the total scores of the remaining 15 (79%) ranged from 1 to 8.

Conclusion

While several studies have audited open science practices across discipline-specific journals, none have focused on CAIM journals. The results of this study indicate that CAIM journals provide minimal guidelines to encourage or require authors to adhere to open science practices and there is an opportunity to improve the use of open science practices in the field.
Exploring best practice governance for EU-funded health research consortia: A qualitative study protocol for insight and ideation
Authors: Renker-Darby Ana , Bärnighausen Till , Neumann Christine , Preet Raman , Treskova Marina
Published: December 2023

Background

International consortia have emerged as a common model to organise and fund large-scale, multi-disciplinary research in contemporary health and biomedical science. The diversity of participants, size and complexity of these consortia necessitates effective governance to achieve their research aims and societal impact. For health research consortia funded by the European Union, certain governance structures and processes have emerged out of convention. However, there is limited scientific evidence to support their use, and little is known about consortia participants’ perspectives on how governance structures could be improved to better serve the implementation of research. In this paper, we present a protocol for a qualitative study to explore the perspectives of participants in European Union-funded health research consortia on the value of governance structures and how they might be improved.

Methods and analysis

We will conduct a qualitative study using in-depth interviews with participants in health research consortia funded by the European Union. We will recruit participants following a purposeful sampling approach, and recruitment will continue until saturation is reached. During in-depth interviews, we will ask participants about how the governance of consortia is structured and what is working well or poorly about those governance structures from their perspective. We will draw on design thinking methods to help participants to ideate improvements in governance structures. Data will be analysed using a thematic analysis approach.

Discussion

Findings from this study will provide valuable evidence for developing and formulating governance structures for health research consortia. The findings of this work may also contribute to guidelines for consortium proposal submissions.
Clinical risk factors and blood protein biomarkers of 10-year pneumonia risk
Authors: Lee Ming-Ming , Zuo Yi , Steiling Katrina , Mizgerd Joseph P. , Kalesan Bindu , Walkey Allan J.
Published: December 2023

Background

Chronic inflammation may increase susceptibility to pneumonia.

Research Question

To explore associations between clinical comorbidities, serum protein immunoassays, and long-term pneumonia risk.

Methods

Framingham Heart Study Offspring Cohort participants ≥65 years were linked to their Centers for Medicare Services claims data. Clinical data and 88 serum protein immunoassays were evaluated for associations with 10-year incident pneumonia risk using Fine-Gray models for competing risks of death and least absolute shrinkage and selection operators for covariate selection.

Results

We identified 1,370 participants with immunoassays and linkage to Medicare data. During 10 years of follow up, 428 (31%) participants had a pneumonia diagnosis. Chronic pulmonary disease [subdistribution hazard ratio (SHR) 1.87; 95% confidence interval (CI), 1.33-2.61], current smoking (SHR 1.79, CI 1.31-2.45), heart failure (SHR 1.74, CI 1.10-2.74), atrial fibrillation/flutter (SHR 1.43, CI 1.06-1.93), diabetes (SHR 1.36, CI 1.05-1.75), hospitalization within one year (SHR 1.34, CI 1.09-1.65), and age (SHR 1.06 per year, CI 1.04-1.08) were associated with pneumonia. Three baseline serum protein measurements were associated with pneumonia risk independent of measured clinical factors: growth differentiation factor 15 (SHR 1.32; CI 1.02-1.69), C-reactive protein (SHR 1.16, CI 1.06-1.27) and matrix metallopeptidase 8 (SHR 1.14, CI 1.01-1.30). Addition of C-reactive protein to the clinical model improved prediction (Akaike information criterion 4950 from 4960; C-statistic of 0.64 from 0.62).

Conclusions

Clinical comorbidities and serum immunoassays were predictive of pneumonia risk. C-reactive protein, a routinely-available measure of inflammation, modestly improved pneumonia risk prediction over clinical factors. Our findings support the hypothesis that prior inflammation may increase the risk of pneumonia.

Summary or “take home” message

Here, we show that long-term pneumonia risks are associated with clinical characteristics and serum markers of inflammation. Our findings offer preliminary support to the hypothesis that chronic inflammation may be a marker of increased pneumonia risk.
A low-cost culture- and DNA extraction-free method for the molecular detection of pneumococcal carriage in saliva
Authors: Peno Chikondi , Lin Tzu-Yi , Hislop Maikel S. , Yolda-Carr Devyn , Farjado Katherine , York Anna , Pitzer Virginia E. , Weinberger Daniel M. , Bei Amy K. , Allicock Orchid M. , Wyllie Anne L.
Published: December 2023

Background

Molecular methods have improved the sensitivity of detection of pneumococcal carriage in saliva. However, they typically require sample culture-enrichment and nucleic acid extraction, prior to performing the detection assay. These factors may limit scalability for extensive surveillance of pneumococcus, particularly in low-resource settings. In this study, we evaluated the performance of a DNA-extraction-free method for the detection of pneumococcus in saliva.

Methods

We developed a streamlined qPCR-based protocol for the detection of pneumococcus, omitting culture-enrichment and DNA extraction. Using saliva samples collected from children attending childcare centers (New Haven, CT, USA), we evaluated detection of pneumococcus using saliva lysates as compared to purified DNA extracted from culture-enriched aliquots of the paired samples using qPCR targeting the pneumococcalpiaBgene.

Results

Of 759 saliva samples tested from 92 children (median age 3.65 years; IQR (2.46-4.78), pneumococcus was detected in 358 (47.2%) saliva lysates prepared using the extraction-free protocol and in 369 (48.6%) DNA extracted from the culture-enriched samples. We observed a near-perfect agreement between the two protocols (Cohen’s kappa: 0.92; 95%CI: 0.90-0.95). While we also observed a high correlation between the qPCR CTvalues generated by the two methods (r=0.93,p<0.0001), the CTvalues generated from the extraction-free, saliva lysates were higher (lower concentration) than those obtained from DNA extracted from culture-enriched samples (ΔCT= 6.68,p<0.00001).

Conclusions

For pneumococcal carriage surveillance in children, our findings suggest that a DNA extraction-free approach may offer a cost-effective alternative to the resource-intensive culture-enrichment method. While, as expected, we observed higher qPCR CTvalues (lower bacterial load) in the absence of culture-enrichment, the overall rate of detection remained unaffected.
Buried or Exposed Kirschner Wire for the Management of Hand and Forearm Fractures: A Systematic Review, Meta-Analysis, and Meta-Regression
Authors: Hidajat Nucki Nursjamsi , Magetsari RM. Satrio Nugroho , Prasetiyo Gregorius Thomas , Respati Danendra Rakha Putra , Tjandra Kevin Christian
Published: December 2023

Background

The recommendation on whether to bury or expose the Kirschner wire (K-wire) for the management of fractures has still been controversial with inconsistent results in the published studies. This study aims to summarize the comparison between buried and exposed K-wire for the management of hand and forearm fractures.

Methods

We conducted relevant literature searches on Europe PMC, Medline, Scopus, and Cochrane Library databases using specific keywords. The results of continuous variables were pooled into the standardized mean difference (SMD), while dichotomous variables were pooled into odds ratio (OR) along with 95% confidence intervals (95% CI) using random-effect models.

Results

A total of 11 studies were included. Our pooled analysis revealed that buried K-wire was associated with a lower risk of pin site infection [RR 0.49 (95% CI 0.36 – 0.67),p< 0.00001,I2= 0%] and longer duration until pin removal [MD 33.85 days (95% CI 18.68 – 49.02),p< 0.0001,I2= 99%] when compared with exposed K-wire. However, the duration of surgery was significantly longer in the buried K-wire [MD 6.98 minutes (95% CI 2.19 – 11.76),p= 0.004,I2= 42%] with no significant difference in the early pin removal rate [RR 0.73 (95% CI 0.36 – 1.45),p= 0.37,I2= 0%]. Further regression analysis revealed that sample size, age, sex, and duration of follow-up did not affect those relationships.

Conclusion

Buried K-wire may offer benefits in reducing the infection rate with a longer duration until pin removal. However, further RCTs with larger sample sizes are still needed to confirm the results of our study.
Exploring factors influencing user perspective of ChatGPT as a technology that assists in healthcare decision making: A cross sectional survey study
Authors: Choudhury Avishek , Elkefi Safa , Tounsi Achraf
Published: December 2023

As ChatGPT emerges as a potential ally in healthcare decision-making, it is imperative to investigate how users leverage and perceive it. The repurposing of technology is innovative but brings risks, especially since AI’s effectiveness depends on the data it’s fed. In healthcare, where accuracy is critical, ChatGPT might provide sound advice based on current medical knowledge, which could turn into misinformation if its data sources later include erroneous information. Our study assesses user perceptions of ChatGPT, particularly of those who used ChatGPT for healthcare-related queries. By examining factors such as competence, reliability, transparency, trustworthiness, security, and persuasiveness of ChatGPT, the research aimed to understand how users rely on ChatGPT for health-related decision-making. A web-based survey was distributed to U.S. adults using ChatGPT at least once a month. Data was collected from February to March 2023. Bayesian Linear Regression was used to understand how much ChatGPT aids in informed decision-making. This analysis was conducted on subsets of respondents, both those who used ChatGPT for healthcare decisions and those who did not. Qualitative data from open-ended questions were analyzed using content analysis, with thematic coding to extract public opinions on urban environmental policies. The coding process was validated through inter-coder reliability assessments, achieving a Cohen’s Kappa coefficient of 0.75. Six hundred and seven individuals responded to the survey. Respondents were distributed across 306 US cities of which 20 participants were from rural cities. Of all the respondents, 44 used ChatGPT for health-related queries and decision-making. While all users valued the content quality, privacy, and trustworthiness of ChatGPT across different contexts, those using it for healthcare information place a greater emphasis on safety, trust, and the depth of information. Conversely, users engaging with ChatGPT for non-healthcare purposes prioritize usability, human-like interaction, and unbiased content. In conclusion our study findings suggest a clear demarcation in user expectations and requirements from AI systems based on the context of their use.
Enhancing Patient Safety in Opioid Prescribing: A Systematic Review of Potential Indicators
Authors: Bansal Neetu , Khawagi Wael Y. , Shang Nan , Chen Li-Chia
Published: December 2023

Background

This systematic review aimed to identify a comprehensive list of prescribing safety indicators for opioids in any setting from published literature.

Methods

Literature that reported prescribing indicators from 1990-2019 was retrieved from a published systematic review. A subsequent search was conducted from seven electronic databases to identify additional studies from 2019 to 2022. Potential opioid safety prescribing indicators were extracted from studies that reported prescribing indicators of non-injectable opioids and narcotics prescribed to adults with or without specific conditions, concomitant medications, or laboratory monitoring with concerns about the potential safety risk of harm. Retrieved indicators were split by each opioid and merged for the same drugs. Identified indicators were categorised by the type of problem, medication, patient condition/disease, and the risk of the indicators.

Results

Of the 107 indicators retrieved from 48 included articles, 71 were included. Thirty-five (49.3%) opioid prescribing indicators focused on a specific class of opioids, i.e., ‘opioids’ (n=30, 42.3%) and ‘strong opioids’ (n=5, 7.0%); tramadol and fentanyl were the most commonly reported drug (n=6, 8.5%). The indicators account for six types of problems: medication inappropriate to the population (n=16), omission (n=7), inappropriate duration (n=4), inadequate monitoring (n=7), drug-disease interaction (n=16), and drug-drug interaction (n=27). Of all indicators, older age (over 65) is the most common risk factor (n=34, 47.9%). Central nervous system-related adverse effects are the risk of concern for the 27 indicators associated with drug-drug interaction (n=24, 88.9%). Besides, five of the six ‘omission’ indicators are related to ‘without using laxatives’.

Conclusion

This review identified a comprehensive list of indicators that can be applied to flag patients with a high risk of opioid-related harm to facilitate complex decision-making in optimising opioids for pain management. Further research is needed to validate and determine the feasibility of identifying hazardous prescribing in various care settings.
Comparison of the diagnostic accuracy among GPT-4 based ChatGPT, GPT-4V based ChatGPT, and radiologists in musculoskeletal radiology
Authors: Horiuchi Daisuke , Tatekawa Hiroyuki , Oura Tatsushi , Shimono Taro , Walston Shannon L , Takita Hirotaka , Matsushita Shu , Mitsuyama Yasuhito , Miki Yukio , Ueda Daiju
Published: December 2023

Objective

To compare the diagnostic accuracy of Generative Pre-trained Transformer (GPT)-4 based ChatGPT, GPT-4 with vision (GPT-4V) based ChatGPT, and radiologists in musculoskeletal radiology.

Materials and Methods

We included 106 “Test Yourself” cases fromSkeletal Radiologybetween January 2014 and September 2023. We input the medical history and imaging findings into GPT-4 based ChatGPT and the medical history and images into GPT-4V based ChatGPT, then both generated a diagnosis for each case. Two radiologists (a radiology resident and a board-certified radiologist) independently provided diagnoses for all cases. The diagnostic accuracy rates were determined based on the published ground truth. Chi-square tests were performed to compare the diagnostic accuracy of GPT-4 based ChatGPT, GPT-4V based ChatGPT, and radiologists.

Results

GPT-4 based ChatGPT significantly outperformed GPT-4V based ChatGPT (p< 0.001) with accuracy rates of 43% (46/106) and 8% (9/106), respectively. The radiology resident and the board-certified radiologist achieved accuracy rates of 41% (43/106) and 53% (56/106). The diagnostic accuracy of GPT-4 based ChatGPT was comparable to that of the radiology resident but was lower than that of the board-certified radiologist, although the differences were not significant (p= 0.78 and 0.22, respectively). The diagnostic accuracy of GPT-4V based ChatGPT was significantly lower than those of both radiologists (p< 0.001 and < 0.001, respectively).

Conclusion

GPT-4 based ChatGPT demonstrated significantly higher diagnostic accuracy than GPT-4V based ChatGPT. While GPT-4 based ChatGPT’s diagnostic performance was comparable to radiology residents, it did not reach the performance level of board-certified radiologists in musculoskeletal radiology.