bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and monitoring utility of glycated albumin among diabetic patients attending clinic in tertiary hospitals in Dodoma, Tanzania: A cross-sectional study protocol
Authors: Mkumbi George Gabriel , Boaz Matobogolo
Published: July 2023

Diabetes mellitus is a serious public health concern, with third world nations accounting for 80% of the new cases. Tanzania has a high diabetes burden, with rising prevalence, complications, and death, as well as life-threatening impairments. Diabetic diagnosis and prognosis are currently based on two tests: plasma glucose and glycated hemoglobin (HbA1c). However, other markers of glucose homeostasis, such as fructosamine and glycated albumin (GA), may be seen as an appealing alternative, especially in patients whose HbA1c test is skewed or incorrect. GA appears to have a higher overall diagnostic efficiency than fructosamine in a variety of clinical contexts. Further research is needed to determine whether GA can complement or replace traditional glycemic control measurements like HbA1c, as GA may aid in the therapeutic management of diabetic individuals whose HbA1c levels are unreliable.

Method

A hospital-based cross-sectional analytical study design will be conducted among diabetic patients attending the diabetic clinics of the Dodoma Regional Referral Hospital and Benjamin Mkapa Hospital from 1stAugust to 30thOctober, 2023.All patients with a diagnosis of diabetes mellitus for more than 6 months on medication will be screened for eligibility. Informed consent, history and clinical examination will be obtained in all the patients. All patients will be subjected to voluntary blood sample collection and blood samples obtained will be sent for RBG and HbA1c. Simultaneously the Glycated Albumin levels will be obtained from the same blood samples collected. Standard glycemic status of all patients will be defined as per HbA1c. A level greater than 7% will be considered as a poor indicator, hence poor control in patients with more than six months of treatment. A questionnaire containing both open and closed ended questions will also be used in recording the patient’s response. Analysis including both descriptive and inferential statistics will be computed with SPSS version 28.0. and a predictor variable P<0.05 will be considered as statistically significant.
Validity, reliability, and readability of single-item and short physical activity questionnaires for use in surveillance: a systematic review
Authors: Tcymbal Antonina , Messing Sven , Mait Rachel , Galindo Perez Roberto , Akter Taiyeba , Rakovac Ivo , Gelius Peter , Abu-Omar Karim
Published: July 2023

Background

Accurate and fast measurement of physical activity is important for surveillance. Even though many physical activity questionnaires (PAQ) are currently used in research, it is unclear which of them is the most reliable, valid, and easy to use. This systematic review aimed to identify existing brief PAQs, describe and compare their measurement properties, and assess their level of readability.

Methods

We performed a systematic review based on the PRISMA statement. Literature searches were conducted in six scientific databases in March 2022. Articles were included if they evaluated validity and/or reliability of brief (i.e., with a maximum of three questions) physical activity or exercise questionnaires intended for healthy adults. Due to the heterogeneity of studies, data were summarized narratively. The level of readability was calculated according to the Flesch-Kincaid formula.

Results

In total, 34 articles published in English or Spanish were included, evaluating 31 distinct brief PAQs. The studies indicated moderate to good levels of reliability for the PAQs. However, the majority of results showed weak validity when validated against objective measurements and demonstrated weak to moderate validity when validated against other PAQs. Most of the assessed PAQs met the criterion of being "short," allowing respondents to complete them in less than one minute either by themselves or with an interviewer. However, only 17 questionnaires had a readability level that indicates that the PAQ is easy to understand for the majority of the population.

Conclusions

This review identified a variety of brief PAQs, but most of them were evaluated in only a single study. The methods used to assess measurement properties varied widely across studies, limiting the comparability between different PAQs and making it challenging to identify a single tool as the most suitable. Furthermore, PAQs employed different concepts for measuring physical activity, necessitating consideration of measurement properties and assessment goals when selecting a specific tool. None of the evaluated brief PAQs allowed for the measurement of whether a person fulfills the main WHO physical activity recommendations. Future development or adaptation of PAQs should prioritize readability as an important factor to enhance their usability.
Internal Validation of Automated Visual Evaluation (AVE) on Smartphone Images for Cervical Cancer Screening in a Prospective Study in Zambia
Authors: Hu Liming , Mwanahamuntu Mulindi H. , Sahasrabuddhe Vikrant V. , Barrett Caroline , Horning Matthew P. , Shah Ishan , Laverriere Zohreh , Banik Dipayan , Ji Ye , Shibemba Aaron Lunda , Chisele Samson , Munalula Mukatimui Kalima , Kaunga Friday , Musonda Francis , Malyangu Evans , Hariharan Karen Milch , Parham Groesbeck P.
Published: July 2023

I.

Objectives

Visual inspection with acetic acid (VIA) is a low-cost approach for cervical cancer screening used in most low- and middle-income countries (LMICs) but, similar to other visual tests like histopathology, is subjective and requires sustained training and quality assurance. We developed, trained, and validated an artificial-intelligence-based “Automated Visual Evaluation” (AVE) tool that can be adapted to run on smartphones to assess smartphone-captured images of the cervix and identify precancerous lesions, helping augment performance of VIA.

Design

Prospective study.

Setting

Eight public health facilities in Zambia.

Participants

8,204 women aged 25-55.

Interventions

Cervical images captured on commonly used low-cost smartphone models were matched with key clinical information including human immunodeficiency virus (HIV) and human papillomavirus (HPV) status, plus histopathology analysis (where applicable), to develop and train an AVE algorithm and evaluate its performance for use as a primary screen and triage test for women who are HPV positive.

Main outcome measures

Area under the receiver operating curve (AUC); sensitivity; specificity.

Results

As a general population screening for cervical precancerous lesions, AVE identified cases of cervical precancerous and cancerous (CIN2+) lesions with high performance (AUC = 0.91, 95% confidence interval [CI] = 0.89 to 0.93), which translates to a sensitivity of 85% (95% CI = 81% to 90%) and specificity of 86% (95% CI = 84% to 88%) based on maximizing the Youden’s index. This represents a considerable improvement over VIA, which a meta-analysis by the World Health Organization (WHO) estimates to have sensitivity of 66% and specificity of 87%. For women living with HIV, the AUC of AVE was 0.91 (95% CI = 0.88 to 0.93), and among those testing positive for high-risk HPV types, the AUC was 0.87 (95% CI = 0.83 to 0.91).

Conclusions

These results demonstrate the feasibility of utilizing AVE on images captured using a commonly available smartphone by screening nurses and support our transition to clinical evaluation of AVE’s sensitivity, specificity, feasibility, and acceptability across a broader range of settings. The performance of the algorithm as reported may be inflated, as biopsies were obtained only from study participants with visible aceto-white cervical lesions, which can lead to verification bias; and the images and data sets used for testing of the model, although “unseen” by the algorithm during training, were acquired from the same set of patients and devices, limiting the study to that of an internal validation of the AVE algorithm.
Development and Validation of a Computable Phenotype for Turner Syndrome Utilizing Electronic Health Records from a National Pediatric Network
Authors: Huang Sarah D. , Bamba Vaneeta , Bothwell Samantha , Fechner Patricia Y. , Furniss Anna , Ikomi Chijioke , Nahata Leena , Nokoff Natalie J , Pyle Laura , Seyoum Helina , Davis Shanlee M
Published: July 2023

Turner syndrome (TS) is a genetic condition occurring in ∼1 in 2,000 females characterized by the complete or partial absence of the second sex chromosome. TS research faces similar challenges to many other pediatric rare disease conditions, with homogenous, single-center, underpowered studies. Secondary data analyses utilizing Electronic Health Record (EHR) have the potential to address these limitations, however, an algorithm to accurately identify TS cases in EHR data is needed. We developed a computable phenotype to identify patients with TS using PEDSnet, a pediatric research network. This computable phenotype was validated through chart review; true positives and negatives and false positives and negatives were used to assess accuracy at both primary and external validation sites. The optimal algorithm consisted of the following criteria: female sex, ≥1 outpatient encounter, and ≥3 encounters with a diagnosis code that maps to TS, yielding average sensitivity 0.97, specificity 0.88, and C-statistic 0.93 across all sites. The accuracy of any estradiol prescriptions yielded an average C-statistic of 0.91 across sites and 0.80 for transdermal and oral formulations separately. PEDSnet and computable phenotyping are powerful tools in providing large, diverse samples to pragmatically study rare pediatric conditions like TS.
Dysregulation of gut microbiota composition in individuals with personality disorders: A systemic review and meta-analysis
Authors: Imran Rangraze , Khan Shehla
Published: July 2023

Background

Anxiety disorders are the most frequent mental comorbidity in people with functional GI difficulties, and abdominal discomfort is one of the most known physical signs of sadness. Successful top-down treatments using antidepressants and psychosocial therapies in the treatment of irritable bowel syndrome (IBS) further define personality illnesses as more than merely CNS disorders, but disorders with highly extensive systemic interconnections.

Therefore, we recently conducted a systematic review of the observational literature comparing the gut microbiota composition of persons with personality difficulties with healthy control.

Methods

This review was written according to the guidelines established by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Not a single rule was broken, yet a more thorough search strategy did provide more relevant results. Pubmed, Scopus, Embase, Web of Science, Ovid, Global Health, PsycINFO, etc. were searched thoroughly using the phrases “gut microbiota, psychological disorders, personality disorders, composition, major depressive disorder, bipolar disorders, schizophrenia, etc.”

Results

Researchers did discover widespread differences in the gut microbiota of patients and controls under each category of personality disorder. They also found that there are distinct bacterial taxa that had differing abundances in patients with these three psychiatric illnesses compared to healthy controls. They found a great deal of variation in study designs and reporting, such as in the inclusion and exclusion of study populations, sampling feces for study of gut microbiota; taking into account or adjusting for important factors known to impact gut microbiota composition; storing feces; processing feces; analyzing feces.

Conclusion

Our systematic review did find that psychological disorders appeared to exhibit different overall compositional differences compared to controls. There was a general trend toward the finding of increased abundances of bacteria involved in glutamate and GABA metabolism, and lower abundances of butyrate-producing bacteria in psychological disorders
Social Cohesion and Covid-19: an integrative review
Authors: Ware Paul
Published: July 2023

Background

Nations of considerable wealth and sophisticated healthcare infrastructures have seen high rates of illness and death from Covid-19. Others with limited economic means and less developed healthcare infrastructures have achieved much lower burdens. In order to build a full understanding, an appraisal of the contribution of social relationships is necessary. Social cohesion represents a promising conceptual tool.

Objective

The aim was to examine scholarship on social cohesion during the Covid-19 pandemic: specifically – the constructions of social cohesion deployed, how it was measured, and the effects of and on social cohesion reported.

Methods

The Pubmed, Scopus and JSTOR databases were searched for relevant journal articles and grey literature. 66 studies met the inclusion criteria. Data were extracted and analysed from these using spreadsheet software.

Results

Several constructions of social cohesion were found. These concerned interpersonal relationships; sameness and difference; collective action; perceptions/emotions of group members; structures and institutions of governance; local or cultural specificity; and hybrid/multidimensional models. Social cohesion was reported as influential on health outcomes, health behaviours, and resilience and emotional wellbeing; but also that there was some potential for it to drive undesirable outcomes. Scholarship reported increases or decreases in quantitative measures of social cohesion, a temporary ‘rally round the flag’ effect early in the pandemic, the variable impacts of policy on cohesion, and changing interpersonal relationships due to pandemic conditions. There are numerous issues with the literature that reflect the well-documented limitations of popular versions of the social cohesion concept.

Conclusions

Social cohesion has been used to express a range of different aspects of relationships during the pandemic. It is said to promote better health outcomes, more engagement with positive health behaviours, and greater resilience and emotional wellbeing. The literature presents a range of ways in which it has been altered by the pandemic conditions.
Covid-19 related cognitive, structural and functional brain changes among Italian adolescents and young adults: a multimodal longitudinal case-control study
Authors: Invernizzi Azzurra , Renzetti Stefano , van Thriel Christoph , Rechtman Elza , Patrono Alessandra , Ambrosi Claudia , Mascaro Lorella , Cagna Giuseppa , Gasparotti Roberto , Reichenberg Abraham , Tang Cheuk Y. , Lucchini Roberto G. , Wright Robert O. , Placidi Donatella , Horton Megan K.
Published: July 2023

Coronavirus disease 2019 (COVID-19) has been associated with brain functional, structural, and cognitive changes that persist months after infection. Most studies of the neurologic outcomes related to COVID-19 focus on severe infection and aging populations. Here, we investigated the neural activities underlying COVID-19 related outcomes in a case-control study of mildly infected youth enrolled in a longitudinal study in Lombardy, Italy, a global hotspot of COVID-19. All participants (13 cases, 27 controls, mean age 24 years) completed resting state functional (fMRI), structural MRI, cognitive assessments (CANTAB spatial working memory) at baseline (pre-COVID) and follow-up (post-COVID). Using graph theory eigenvector centrality (EC) and data-driven statistical methods, we examined differences in ECdelta(i.e., the difference in EC values pre- and post-COVID-19) and volumetricdelta(i.e., the difference in cortical volume of cortical and subcortical areas pre- and post-COVID) between COVID-19 cases and controls. We found that ECdeltasignificantly between COVID-19 and healthy participants in five brain regions; right intracalcarine cortex, right lingual gyrus, left hippocampus, left amygdala, left frontal orbital cortex. The left hippocampus showed a significant decrease in volumetricdeltabetween groups (p=0.041). The reduced ECdeltain the right amygdala associated with COVID-19 status mediated the association between COVID-19 and disrupted spatial working memory. Our results show persistent structural, functional and cognitive brain changes in key brain areas associated with olfaction and cognition. These results may guide treatment efforts to assess the longevity, reversibility and impact of the observed brain and cognitive changes following COVID-19.
Multiple Biomarkers to Predict Major Adverse Cardiovascular Events in Patients With Coronary Chronic Total Occlusions
Authors: Adusumalli Srikanth , Mohebi Reza , McCarthy Cian P. , Megaret Craig A. , Rhyne Rhonda F. , Jaffer Farouc A. , Januzzi James L.
Published: July 2023

Background

There are limited tools available to predict the long-term prognosis of persons with coronary chronic total occlusions (CTO).

Objectives

We evaluated performance of a blood biomarker panel to predict cardiovascular (CV) events in patients with CTO.

Methods

From 1251 patients in the CASABLANCA study, 241 participants with a CTO were followed for an average of 4 years for occurrence of major adverse CV events (MACE, CV death, non-fatal myocardial infarction or stroke) and CV death/heart failure (HF) hospitalization. Results of a biomarker panel (kidney injury molecule-1, N-terminal pro-B-type natriuretic peptide, osteopontin, and tissue inhibitor of metalloproteinase-1) from baseline samples were expressed as low-, moderate-, and high-risk.

Results

By 4 years, a total of 67 (27.8%) MACE events and 56 (23.2%) CV death/HF hospitalization events occurred. The C-statistic of the panel for MACE through 4 years was 0.79. Considering patients in the low-risk group as a reference, the hazard ratio of MACE by 4 years was 6.65 (95% confidence interval [CI]: 2.98-14.8) and 12.4 (95% CI:5.17-29.6) for the moderate and high-risk groups (both P <0.001). The C-statistic for CVD/HF hospitalization by 4 years was 0.84. Compared to the low-risk score group, the moderate and high-risk groups had hazard ratios of 5.61 (95% CI: 2.33-13.5) and 15.6 (95% CI: 6.18, 39.2; both P value <0.001).

Conclusion

A multiple biomarker panel assists in evaluating the risk of adverse outcomes in patients with coronary CTO. These results may have implications for patient care and could have a role for clinical trial enrichment.

Clinical Trial

CASABLANCA,ClinicalTrials.govIdentifier:NCT00842868
Prevalence of Chronic Rhinosinusitis in Rajavithi Hospital Workers, Bangkok, Thailand
Authors: Chitsuthipakorn Wirach , Naphapunsakul Suphitsara , Korwattanamongkol Patlada , Mongkolkul Kittichai , Chindavijak Somjin
Published: July 2023

Background

The prevalence of chronic rhinosinusitis (CRS) has been reported to range from 5% to 12% in different parts of the world. However, the prevalence of CRS in Thailand has not been investigated. Our objective was to determine the prevalence of CRS among hospital workers and identify any potential problems encountered during the survey.

Method

Adult workers (>18 years) of Rajavithi Hospital, a tertiary hospital in Bangkok, Thailand, were recruited. This cross-sectional survey was conducted from September 2021 to September 2022. The participants were given a link to online questionnaires asking if they had nasal obstruction, discharge, decreased smell sensation, or facial pain and their respective duration. Phone numbers and email were asked for contact when needed. The participants who fulfilled the symptom and duration according to the European position paper on rhinosinusitis and nasal polyp 2020 were counted as symptom-based CRS patients. These patients were then contacted for nasal endoscopy. The endoscopic-based diagnosis of CRS was made after positive endoscopy findings.

Result

A total of 1,025 participants (mean age of 33.7 years) were recruited. Of total, there were 34 (3.3%) and 6 (0.58%) participants fulfilled symptom- and endoscopy-based diagnoses, respectively. Fourteen participants did not respond to calls or emails. Five patients refused to visit the clinic due to inconveniences. One patient refused nasal endoscopy because of the expenses.

Conclusion

The overall prevalence of chronic rhinosinusitis in workers of Rajavithi Hospital, was 3.3% and 0.58% by symptom- and endoscopy-based criteria, respectively. Difficulty reaching the participants for nasal endoscopy was the leading survey problem.
DIMPLE: AN R PACKAGE TO QUANTIFY, VISUALIZE, AND MODEL SPATIAL CELLULAR INTERACTIONS FROM MULTIPLEX IMAGING WITH DISTANCE MATRICES
Authors: Masotti Maria , Osher Nathaniel , Eliason Joel , Rao Arvind , Baladandayuthapani Veerabhadran
Published: July 2023

The tumor microenvironment (TME) is a complex ecosystem containing tumor cells, other surrounding cells, blood vessels, and extracellular matrix. Recent advances in multiplexed imaging technologies allow researchers to map several cellular markers in the TME at the single cell level while preserving their spatial locations. Evidence is mounting that cellular interactions in the TME can promote or inhibit tumor development and contribute to drug resistance. Current statistical approaches to quantify cell-cell interactions do not readily scale to the outputs of new imaging technologies which can distinguish many unique cell phenotypes in one image. We propose a scalable analytical framework and accompanying R package, DIMPLE, to quantify, visualize, and model cell-cell interactions in the TME. In application of DIMPLE to publicly available MI data, we uncover statistically significant associations between image-level measures of cell-cell interactions and patient-level covariates.
Cellular proliferation biases clonal lineage tracing and trajectory inference
Authors: Bonham-Carter Becca , Schiebinger Geoffrey
Published: July 2023

We identify a fundamental statistical phenomenon in single-cell time courses with clone-based lineage tracing. Through simple probabilistic arguments, we show how the relative growth rates of cells influence the probability that they will be sampled in clones observed across multiple time points. We support these arguments with a simple simulation study and a time-course of T-cell development, and we demonstrate that this bias can impact fate probability predictions from trajectory inference methods. Finally, we explore how to develop trajectory inference methods which are robust to this bias. In particular, we show how to extendLineageOT[1] to use data from clones observed across multiple time points.
Host-gut microbiota interactions shape parasite infections in farmed Atlantic salmon
Authors: Brealey Jaelle C. , Kodama Miyako , Rasmussen Jacob A. , Hansen Søren B. , Santos-Bay Luisa , Lecaudey Laurène A. , Hansen Martin , Fjære Even , Myrmel Lene S. , Madsen Lise , Bernhard Annette , Sveier Harald , Kristiansen Karsten , Gilbert M. Thomas P. , Martin Michael D. , Limborg Morten T.
Published: July 2023

Animals and their associated microbiota share long evolutionary histories. Both host genotype and associated microbiota influence phenotypes such as growth and disease resilience. We applied a hologenomic approach to explore the relationship between host and microbiota in shaping lifetime growth and parasitic cestode infection in farmed Atlantic salmon. Genomes, transcriptomes, metabolomes and metagenomes were generated from the guts of 460 harvest-aged salmon, 82% of which were naturally infected with an intestinal cestode. One salmonid-specificMycoplasmadominated the gut microbiota of uninfected salmon. However, the microbiota was perturbed in smaller, parasitised fish, with increased abundance ofVibrionaceaeand otherMycoplasmaspecies previously linked to the cestode microbiota. The cestode-associatedMycoplasmacarry more virulence-associated genes than the salmonidMycoplasma. Colonisation by one cestode-associatedMycoplasmawas associated with a region of the salmon genome encoding several long noncoding RNA genes previously associated with host control of intestinal microbiota. Integrating the multiple omic datasets revealed coordinated changes in the salmon gut transcriptome and metabolome that correlated with shifts in the microbiota of smaller, parasitised fish. Our results suggest that cestode infections introduce new microbes and trigger host responses, altering the gut microbiota with increases in potentially pathogenic microbes. Establishment of these microbes is partially shaped by the genetic background of the host. Our study highlights the value of a hologenomic approach for gaining an in-depth understanding of trilateral interactions among host, microbiota and parasite.
Acetyl-CoA carboxylase 1-dependent lipogenesis drives breast cancer progression
Authors: Tan Keely , Owen Thomas , McEwen Holly P. , Simpson Peter , Hoy Andrew J. , James David E. , Don Anthony S. , Naylor Matthew J.
Published: July 2023

Dysregulation of cellular energetics, including lipid synthesis mediated through de novo lipogenesis, is a feature of many cancers. Here we report that acetyl-coenzyme A carboxylase (ACC) 1, the rate-limiting enzyme of de novo lipogenesis, is a key regulator of breast cancer progression and cancer cell phenotype. Mammary epithelial-specific deletion of ACC1 impaired tumour progression and decreased cancer cell proliferation in the PyMT model of breast cancerin vivo. ACC1 knockout in human breast cancer cell lines resulted in decreased cell number and altered cell and membrane morphology. Lipidomic profiling demonstrated reduced levels of acyl-carnitines (CARs) and several phospholipid (PL) classes, whilst also shifting the lipid profiles to exhibit more elongated and less saturated lipids in ACC1 knockout breast cancer cells. Palmitate rescue of ACC1 deletion phenotypes demonstrated a critical role for ACC1 driven de novo lipogenesis in breast cancer cell function. Analysis of human breast tumour-microarrays identified strong ACC1 expression at all breast cancer stages, grade and metastasis, compared to normal adjacent tissue. Together our data demonstrate a novel role for ACC1 in breast cancer progression and cancer cell function, mediated through its lipogenic role, that together with its expression profile, identify ACC1 as a potential therapeutic target in breast cancer.

Statement of significance

This study investigates the impact of ACC1 deletion in breast cancer progression, revealing the importance of ACC1-derived lipids in breast cancer cell phenotypes and identifies ACC1 as a potential novel therapeutic target.
Upregulated Fcrl5 disrupts B cell anergy and causes autoimmunity
Authors: Ono Chisato , Tanaka Shinya , Myouzen Keiko , Iwasaki Takeshi , Ueda Mahoko , Oda Yoshinao , Yamamoto Kazuhiko , Kochi Yuta , Baba Yoshihiro
Published: July 2023

B cell anergy plays a critical role in maintaining self-tolerance by inhibiting autoreactive B cell activation to prevent autoimmune diseases. Here, we demonstrated that Fc receptor-like 5 (Fcrl5) upregulation contributes to autoimmune disease pathogenesis by disrupting B cell anergy. Fcrl5—a gene whose homologs are associated with human autoimmune diseases—is highly expressed in age/autoimmunity-associated B cells (ABCs), an autoreactive B cell subset. By generating B cell-specific Fcrl5 transgenic mice, we demonstrated that Fcrl5 overexpression in B cells caused systemic autoimmunity with age. Furthermore, Fcrl5 upregulation in B cells exacerbated the systemic lupus erythematosus-like disease model and increased the levels of ABCs and activated T cells. Mechanistically, an increase in Fcrl5 expression broke B cell anergy, activating autoreactive B cells in the presence of a self-antigen. Fcrl5 facilitated toll-like receptor signaling, reactivating anergic B cells. Thus, Fcrl5 is a potential regulator of B cell-mediated autoimmunity by regulating B cell anergy. This study provides important insights into the role of Fcrl5 in breaking B cell anergy and its effect on the pathogenesis of autoimmune diseases.
A paradigm for ethanol consumption in head-fixed mice during prefrontal cortical two-photon calcium imaging
Authors: Kalelkar Anagha , Sipe Grayson , Castro E Costa Ana Raquel , Lorenzo Ilka M. , Nguyen My , Linares-Garcia Ivan , Vazey Elena , Huda Rafiq
Published: July 2023

The prefrontal cortex (PFC) is a hub for higher-level cognitive behaviors and is a key target for neuroadaptations in alcohol use disorders. Preclinical models of ethanol consumption are instrumental for understanding how acute and repeated drinking affects PFC structure and function. Recent advances in genetically encoded sensors of neuronal activity and neuromodulator release combined with functional microscopy (multiphoton and one-photon widefield imaging) allow multimodalin-vivoPFC recordings at subcellular and cellular scales. While these methods could enable a deeper understanding of the relationship between alcohol and PFC function/dysfunction, they require animals to be head-fixed. Here, we present a method in mice for binge-like ethanol consumption during head-fixation. Male and female mice were first acclimated to ethanol by providing home cage access to 20% ethanol (v/v) for 4 or 8 days. After home cage drinking, mice consumed ethanol from a lick spout during head-fixation. We used two-photon calcium imaging during the head-fixed drinking paradigm to record from a large population of PFC neurons (>1000) to explore how acute ethanol affects their activity. Drinking modulated activity rates in a subset of neurons on slow (minutes) and fast (seconds) time scales but the majority of neurons were unaffected. Moreover, ethanol intake did not significantly affect network level interactions in the PFC as assessed through inter-neuronal pairwise correlations. By establishing a method for binge-like drinking in head-fixed mice, we lay the groundwork for leveraging advanced microscopy technologies to study alcohol-induced neuroadaptations in PFC and other brain circuits.

Highlights

C57BL/6J mice voluntarily consume ethanol to binge-like levels during head-fixation, with females consuming more ethanol than males.

Mice show differences in frontloading and licking behavior for head-fixed ethanol and sucrose consumption.

Head-fixed paradigm enables two-photon calcium imaging in the anterior cingulate cortex subdivision of the prefrontal cortex.

Acute ethanol increases and decreases single neuron activity at fast (seconds) and slow (minutes) time scales but does not alter pairwise correlations between neurons.
Identification of five characteristic ferroptosis-related genes as novel biomarkers for ischemic stroke using bioinformatic and machine learning strategies
Authors: Feng Xin , Huang Chunhua , Ye Lin , Xu Zhongbo
Published: July 2023

Ferroptosis is crucial in neuronal cell death, associated with various neurological disorders. However, the role of ferroptosis-related genes (FRGs) in ischaemic stroke (IS) has yet to be well elucidated. We downloaded IS-related gene information and FRGs from the Gene Expression Omnibus (GEO) and Ferritin databases (FerrDb). 22 IS-related DE-FRGs were obtained. Functional enrichment analysis showed that these genes involve multiple regulatory pathways related to IS pathogenesis, including redox, amino acid metabolism, and cell cycle. Subsequently, DUOX2, MDM2, EGFR, MAP3K14, and TRIM46 were identified as core marker genes among the 22 DE-FRGs by lasso and SVM-RFE algorithms. The construction of the nomogram using the five marker genes had excellent diagnostic value. In addition, CIBERSORT analysis showed that changes in the immune microenvironment of IS patients might be associated with TRIM46, MDM2, and DUOX2. In addition, a total of 66 drugs targeting two characteristic FRGs were obtained. The ceRNA networks revealed complex regulatory relationships based on characteristic FRGs. These findings provide new insights into the diagnosis and treatment of IS.
Season-dependent processing of innate conspecific vocalizations in the male and female European starling (Sturnus vulgaris)
Authors: Vidas-Guscic N.D. , Jonckers E. , Van Audekerke J. , Orije J. , Hamaide J. , Majumdar G. , Verhoye M. , Van der Linden A.
Published: July 2023

Avian innate nestling begging calls are similar to human infant cries in the behavioral response they elicit. However, it remains unknown whether the auditory processing of innate begging calls changes in seasonal songbirds from non-breeding to breeding season when hormonal neuromodulation of the auditory forebrain occurs.

An fMRI experiment was set up to expose male and female European starlings (Sturnus vulgaris) to recordings of seasonal conspecific nestling begging calls in the breeding and non-breeding season. This response was compared with their response to conspecific warble motifs and artificial pure tones, both proven seasonally invariable at least in the male starling’s neural response.

Our results demonstrate significant seasonal variation in auditory forebrain responses exclusively elicited by begging calls and not by the applied control stimuli. Right Field L and the Caudomedial Nidopallium (NCM) seemed, irrespective of season or sex, more sensitive in response to begging than to control stimuli. A seasonal differential response specifically to begging calls was found in both sexes in a ventral midsagittal region of NCM.

Our findings thereby support the functional fine-tuning of vocal communications between sender and receiver in a breeding context for innate vocalizations and are in line with the bi-parenting behavior in this species.
Evolutionary trade-offs in dormancy phenology
Authors: Constant Théo , Dobson F. Stephen , Habold Caroline , Giroud Sylvain
Published: July 2023

Seasonal animal dormancy, hibernation or diapause, is widely interpreted as a physiological response for surviving energetic challenges during the harshest times of the year (the physiological constraint hypothesis). However, there are other mutually non-exclusive hypotheses to explain the timing of animal dormancy, that is, entry into and emergence from hibernation (i.e. dormancy phenology). Other survival advantages of dormancy that have been proposed are reduced risks of predation and competition (the “life-history” hypothesis), but comparative tests across animal species are not yet available. Under this hypothesis, dormancy phenology is influenced by a trade-off between reproductive advantages of being active and survival benefits of dormancy. Within a species, males and females differ in the amount of time and energy they invest in reproduction. Thus, the trade-off between reproduction and survival may be reflected by within-species sex differences in the phenology of dormancy. To examine this hypothesis, we used two complementary approaches: (i) a set of phylogenetic comparative analyses on mammals (mainly holarctic rodents), and (ii) a comparison between endotherm and ectotherm dormancy, via analyses of endotherms (including mainly holoarctic rodents) and the existing literature on ectotherms.

Using the phylogenetic comparative method applied to more than 20 hibernating mammalian species, we found support for both hypotheses as explanations for the phenology of dormancy. In accordance with the life history hypotheses, sex differences in emergence and immergence were favored by the sex difference in reproductive effort. In addition, physiological constraint may influence the trade-off between survival and reproduction such that, low temperature and precipitation as well as smaller body mass influence sex differences in phenology. We also compiled initial evidence that ectotherm dormancy (invertebrates and reptiles) may be 1) less temperature dependent than previously thought and 2) associated with trade-offs consistent with the life history hypothesis. Dormancy in some endotherms and ectotherms show staggered phenology with respect to the growing season (earlier emergence and immergence than expected) which illustrates the selection pressure exerted by the trade-off between reproduction (earlier emergence than expected) and adult survival (earlier immergence than expected). Thus, dormancy during non-life-threatening periods that are unfavorable for reproduction may be more widespread than previously appreciated.
Diagnostic histone modification analysis of individual preimplantation embryos
Authors: Zeng Yiren , Hoshino Yoichiro , Susami Kazuki , Honda Shinnosuke , Minami Naojiro , Ikeda Shuntaro
Published: July 2023

Background

We previously reported a modification of the CUT&Tag method (NTU-CAT) that allows genome-wide histone modification analysis in individual preimplantation embryos. In the present study, NTU-CAT was further simplified by taking advantage of the Well-of-the-Well (WOW) system, which enables the processing of multiple embryos in a shorter time with less reagent and cell loss during the procedure (WOW-CUT&Tag, WOW-CAT).

Results

WOW-CAT allowed histone modification profiling from not only a single blastocyst but also from a portion of it. WOW-CAT generated similar H3K4me3 profiles as NTU-CAT, but they were closer to the profiles produced by chromatin immunoprecipitation-sequencing, such as a valley-like trend, indicating that WOW-CAT may attenuate the bias of Tn5 transposase to cut open chromatin regions. Simultaneous WOW-CAT of two halves of single blastocysts was conducted to analyze two different histone modifications (H3K4me3 and H3K27ac) within the same embryo. Furthermore, trophectoderm cells were biopsied and subjected to WOW-CAT in anticipation of preimplantation diagnosis of histone modifications. WOW-CAT allowed the monitoring of epigenetic modifications in the main body of the embryo. For example, analysis of H3K4me3 modifications ofXISTandDDX3Yin trophectoderm biopsies could be used to sex embryos in combination with quantitative PCR, but without the need for deep sequencing.

Conclusions

These results suggest the applicability of WOW-CAT for flexible epigenetic analysis of individual embryos in preimplantation epigenetic diagnosis.
Functional Regulation of Aquaporin Dynamics by Lipid Bilayer Composition
Authors: Nguyen Anh T. P. , Weigle Austin T. , Shukla Diwakar
Published: July 2023

With the diversity of lipid-protein interactions, any observed membrane protein dynamics or functions directly depend on the lipid bilayer selection. However, the implications of lipid bilayer choice are seldom considered unless characteristic lipid-protein interactions have been previously reported. Using molecular dynamics simulation, we characterize the effects of membrane embedding on plant aquaporin SoPIP2;1, which has no reported high-affinity lipid interactions. The regulatory impacts of a realistic lipid bilayer, and nine different homogeneous bilayers, on varying SoPIP2;1 dynamics were examined. We demonstrate that SoPIP2;1s structure, thermodynamics, kinetics, and water transport are altered as a function of each membrane construct’s ensemble properties. Notably, the realistic bilayer provides stabilization of non-functional SoPIP2;1 metastable states. Hydrophobic mismatch and lipid order parameter calculations further explain how lipid ensemble properties manipulate SoPIP2;1 behavior. Our results illustrate the importance of careful bilayer selection when studying membrane proteins. To this end, we advise cautionary measures when performing membrane protein molecular dynamics simulations.
Spatial Modeling of Sociodemographic Risk for COVID-19 Mortality
Authors: Seamon Erich , Ridenhour Benjamin J. , Miller Craig R. , Johnson-Leung Jennifer
Published: July 2023

In early 2020, the Coronavirus Disease 19 (COVID-19) rapidly spread across the United States (US), exhibiting significant geographic variability. While several studies have examined the predictive relationships of differing factors on COVID-19 deaths, few have looked at spatiotemporal variation at refined geographic scales. The objective of this analysis is to examine this spatiotemporal variation in COVID-19 deaths with respect to association with socioeconomic, health, demographic, and political factors. We use multivariate regression applied to Health and Human Services (HHS) regions as well as nationwide county-level geographically weighted random forest (GWRF) models. Analyses were performed on data from three separate time frames which correspond to the spread of distinct viral variants in the US: pandemic onset until May 2021, May 2021 through November 2021, and December 2021 until April 2022. Multivariate regression results for all regions across three time windows suggest that existing measures of social vulnerability for disaster preparedness (SVI) are predictive of a higher degree of mortality from COVID-19. In comparison, GWRF models provide a more robust evaluation of feature importance and prediction, exposing the value of local features for prediction, such as obesity, which is obscured by coarse-grained analysis. Overall, GWRF results indicate that this more nuanced modeling strategy is useful for determining the spatial variation in the importance of sociodemographic risk factors for predicting COVID-19 mortality.
Harnessing ChatGPT and GPT-4 for Evaluating the Rheumatology Questions of the Spanish Access Exam to Specialized Medical Training
Authors: Madrid-García Alfredo , Rosales-Rosado Zulema , Freites-Nuñez Dalifer , Pérez-Sancristobal Inés , Pato-Cour Esperanza , Plasencia-Rodríguez Chamaida , Cabeza-Osorio Luis , León-Mateos Leticia , Abasolo-Alcázar Lydia , Fernández-Gutiérrez Benjamín , Rodríguez-Rodríguez Luis
Published: July 2023

The emergence of Large Language Models (LLM) with remarkable performance such as ChatGPT and GPT-4, has led to an unprecedented uptake in the population. One of their most promising and studied applications concerns education due to their ability to understand and generate human-like text, creating a multitude of opportunities for enhancing educational practices and outcomes. The objective of this study is two-fold: to assess the accuracy of ChatGPT/GPT-4 in answering rheumatology questions from the access exam to specialized medical training in Spain (MIR), and to evaluate the medical reasoning followed by these LLM to answer those questions. A dataset, RheumaMIR, of 145 rheumatology-related questions, extracted from the exams held between 2010 and 2023, was created for that purpose, used as a prompt for the LLM, and was publicly distributed. Six rheumatologists with clinical and teaching experience evaluated the clinical reasoning of the chatbots using a 5-point Likert scale and their degree of agreement was analyzed. The association between variables that could influence the models’ accuracy (i.e., year of the exam question, disease addressed, type of question and genre) was studied. ChatGPT demonstrated a high level of performance in both accuracy, 66.43%, and clinical reasoning, median (Q1-Q3), 4.5 (2.33-4.67). However, GPT-4 showed better performance with an accuracy score of 93.71% and a median clinical reasoning value of 4.67 (4.5-4.83). These findings suggest that LLM may serve as valuable tools in rheumatology education, aiding in exam preparation and supplementing traditional teaching methods.

What is already known on this topic

Large Language Models have demonstrated remarkable performance when presented with medical exam questions. However, no study has evaluated their clinical reasoning in the rheumatology field.

What this study adds

This is the first study to evaluate the accuracy and clinical reasoning of ChatGPT and GPT-4 when rheumatology questions from an official access exam to specialized medical training are used as prompts.

How this study might affect research, practice or policy?

This study highlights the usefulness of two Large Language Models, ChatGPT and GPT-4, in the training of medical students in the field of rheumatology.

Highlights

ChatGPT showed an accuracy of 66.43% in answering MIR questions, while GPT-4 exhibits a significantly higher proficiency with an accuracy of 93.71%.

The median (Q1-Q3) value of the average score for the clinical reasoning of GPT-4 was 4.67 (4.5-4.83), while for ChatGPT was 4.5 (2.33-4.67).
Cortical thickness alterations and systemic inflammation define long-COVID patients with cognitive impairment
Authors: Besteher Bianca , Rocktäschel Tonia , Garza Alejandra P. , Machnik Marlene , Ballez Johanna , Helbing Dario-Lucas , Finke Kathrin , Reuken Philipp , Güllmar Daniel , Gaser Christian , Walter Martin , Opel Nils , Dunay Ildiko Rita
Published: July 2023

As the heterogeneity of symptoms is increasingly recognized among long-COVID patients, it appears highly relevant to study potential pathophysiological differences along the different subtypes. Preliminary evidence suggests distinct alterations in brain structure and systemic inflammatory patterns in specific groups of long-COVID patients.

To this end, we analyzed differences in cortical thickness and peripheral immune signature between clinical subgroups based on 3T-MRI scans and signature inflammatory markers in n=120 participants comprising healthy never-infected controls, healthy COVID-19 survivors, and subgroups of long-COVID patients with and without cognitive impairment according to screening with Montreal Cognitive Assessment. Whole-brain comparison of cortical thickness between the 4 groups was conducted by surface-based morphometry.

We identified distinct cortical areas showing a progressive increase in cortical thickness across different groups, starting from healthy individuals who had never been infected with COVID-19, followed by healthy COVID-19 survivors, long-COVID patients without cognitive deficits (MoCA ≥ 26), and finally, long-COVID patients exhibiting significant cognitive deficits (MoCA < 26). These findings highlight the continuum of cortical thickness alterations associated with COVID-19, with more pronounced changes observed in individuals experiencing cognitive impairment (p<0.05, FWE-corrected). Affected cortical regions covered prefrontal and temporal gyri, insula, posterior cingulate, parahippocampal gyrus, and parietal areas. Additionally, we discovered a distinct immunophenotype, with elevated levels of IL-10, IFNγ, and sTREM2 in long-COVID patients, especially in the group suffering from cognitive impairment.

We demonstrate lingering cortical and immunological alterations in healthy and impaired subgroups of COVID-19 survivors. This implies a complex underlying pathomechanism in long-COVID and emphasizes the necessity to investigate the whole spectrum of post-COVID biology to determine targeted treatment strategies targeting specific sub-groups.
Relationship between topological efficiency of white matter structural connectome and plasma biomarkers across Alzheimer’s disease continuum
Authors: Zhang Mingkai , Chen Haojie , Huang Weijie , Guo Tengfei , Ma Guolin , Han Ying , Shu Ni
Published: July 2023

Introduction

The associations between plasma AD biomarkers, brain network topology, and cognition across AD continuum remained unknown.

Methods

From the cohort of Sino Longitudinal Study of Cognitive Decline, we analyzed plasma biomarkers of 287 participants, including the levels of β-amyloid (Aβ), phosphorylated-tau181 (p-tau181), glial-fibrillary-acidic-protein (GFAP), and neurofilament-light-chain (NfL), and we assessed white matter network efficiency of 395 participants. Trend analyses evaluated the sensitivity of plasma markers and network efficiency with AD progression. Correlation and mediation analyses further explored the relationships among plasma markers, network efficiency, and cognition across AD continuum.

Results

Among the plasma markers, GFAP exhibited the highest sensitivity with AD progression, followed by NfL, p-tau18, and Aβ42/Aβ40. Local efficiency decreased in multiple brain regions and correlated with GFAP, NfL, and p-tau181. Network efficiency mediated the relationship between plasma markers and cognition.

Discussion

Our findings highlight the potential of network-plasma approaches for early detection and intervention of AD.