bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvement in CD4 count among people with HIV in New York City, 2007-2021: a serial cross-sectional analysis
Authors: Xia Qiang , Farovitch Lorne , Bertolino Daniel , Romano Anthony , Huang Jamie , Misra Kavita , Torian Lucia V. 
Published: August 2023

Background:
A higher CD4 count among people with HIV (PWH) is associated with improved immune function and reduced HIV-related morbidity and mortality. The purpose of this analysis is to report the trend in CD4 count among PWH in New York City (NYC).

Methods:
We conducted a serial cross-sectional analysis using the NYC HIV registry data and reported the proportion of PWH with a CD4 count of 500 cells/mm3 or above, overall and by sex, race or ethnicity, and age.

Results:
The overall proportion of PWH in NYC with a CD4 count of 500 cells/mm3 or above increased from 38.1% in 2007 to 63.8% in 2021. Among males, the proportion increased from 36.7% in 2007 to 62.3% in 2021 with an annual percentage change (APC) of 6.6% (95% CI: 5.8, 7.5) in 2007–2013 and 2.6% (95% CI: 0.7, 4.4) in 2013–2017, and no changes in 2017–2021 (APC: 0.0%; 95% CI: -1.1, 1.0); among females, the proportion increased from 41.0% in 2007 to 67.6% in 2021 with an APC of 7.5% (95% CI: 5.2, 9.8) in 2007–2010, 4.5% (95% CI: 3.5, 5.4) in 2010–2015, and 0.8% (95% CI: 0.4, 1.2) in 2015–2021. White people had a higher proportion than other racial/ethnic groups, 70.9%, 59.3%, 60.9%, and 61.7%, respectively, among White, Black, Latino/Hispanic, and Asian/Pacific Islander males, and 69.8%, 68.0%, 66.3%, and 69.3%, respectively, among White, Black, Latina/Hispanic, and Asian/Pacific Islander females in 2021.

Conclusions:
CD4 count among PWH in NYC improved during 2007–2021, but the improvement slowed in recent years.
Vaginal microbiome, antiretroviral concentrations, and HIV genital shedding in the setting of hormonal contraception initiation in Malawi
Authors: Lantz Alyssa M. , Cottrell Mackenzie L. , Corbett Amanda H. , Chinula Lameck , Kourtis Athena P. , Nelson Julie AE. , Tegha Gerald , Hurst Stacey , Gajer Pawel , Ravel Jacques , Haddad Lisa B. , Tang Jennifer H. , Nicol Melanie R. 
Published: August 2023

Objective:
To understand how vaginal microbiota composition affects antiretroviral concentrations in the setting of hormonal contraception initiation.

Methods:
Cervicovaginal fluid (CVF) concentrations of tenofovir, lamivudine, and efavirenz from 73 Malawian women living with HIV were compared before and after initiation of depot-medroxyprogesterone acetate (DMPA) or levonorgestrel implant. We evaluated antiretroviral concentrations and vaginal microbiota composition/structure in the context of contraception initiation and predicted genital shedding using multivariable repeated measurements models fit by generalized estimating equations.

Results:
Mean lamivudine CVF concentrations decreased 37% 1 month after contraception initiation. Subgroup analyses revealed a 41% decrease in women 1 month after initiating levonorgestrel implant, but no significant difference was observed in DMPA group alone. Tenofovir, lamivudine, and efavirenz CVF concentrations were positively correlated with anaerobic bacteria associated with non-optimal vaginal microbiota. Risk of genital HIV shedding was not significantly associated with tenofovir or lamivudine CVF concentrations (tenofovir RR: 0.098, p = 0.75; lamivudine RR: 0.142, p = 0.54). Lack of association between genital HIV shedding and efavirenz CVF concentrations did not change when adjusting for vaginal microbiota composition, and lamivudine/tenofovir CVF concentrations (RR: 1.33, p = 0.531).

Conclusion:
No effect of hormone initiation on genital shedding provides confidence that women with HIV on either DMPA or levonorgestrel implant contraception will not have compromised ART efficacy. The unexpected positive correlation between antiretroviral CVF concentrations and certain bacterial taxa relative abundance requires further work to understand the mechanism and clinical relevance.
Awareness of Disease and Its Domains in Young-onset and Late-onset Dementia
Authors: Baptista Maria Alice Tourinho , Lacerda Isabel Barbeito , Belfort Tatiana , Nogueira Marcela Moreira Lima , de Oliveira Silva Felipe , Dourado Marcia Cristina Nascimento 
Published: August 2023

Introduction:
Executive function (EF) involves a general cognitive process linked to strategic organization and control of complex goal-oriented tasks. In young-onset dementia (YOD), especially Alzheimer’s disease, the symptoms that stand out in the initial stage are deficits in attention, visual-spatial function, praxis, and language. The present study aims to investigate what components of EF differ in young and late-onset dementia (LOD) and its impact on awareness and its domains.

Methods:
Using a cross-sectional design, we included 44 people with YOD and 70 with LOD. We assessed awareness and its domains, cognition, dementia severity, EF, functionality, and neuropsychiatric symptoms.

Results:
The YOD group was more impaired in general cognition (P=0.017) and had a worse performance in Wechsler Digit Span Backward (DSB) (P=0.007) and Phonemic fluency task (FAS) (P=0.046) tests. In the LOD group, deficits in EF had a greater impact on awareness and on most domains (awareness total score, cognitive functioning and health condition, functional activity impairments and social function).

Conclusions:
Our study findings support the heterogeneity of awareness, not only with regard to the difference between the domains and the measures of EF, but also to the groups studied.
Visuospatial and Verbal Memory Differences in Amish Individuals With Alzheimer Disease and Related Dementias
Authors: Prough Michael B. , Zaman Andrew , Caywood Laura J. , Clouse Jason E. , Herington Sharlene D. , Slifer Susan H. , Dorfsman Daniel A. , Adams Larry A. , Laux Reneé A. , Song Yeunjoo E. , Lynn Audrey , Fuzzell Denise , Fuzzell Sarada L. , Miller Sherri D. , Miskimen Kristy , Main Leighanne R. , Osterman Michael D. , Ogrocki Paula , Lerner Alan J. , Vance Jeffery M. , Haines Jonathan L. , Scott William K. , Pericak-Vance Margaret , Cuccaro Michael L. 
Published: August 2023

Background:
Verbal and visuospatial memory impairments are common to Alzheimer disease and Related Dementias (ADRD), but the patterns of decline in these domains may reflect genetic and lifestyle influences. The latter may be pertinent to populations such as the Amish who have unique lifestyle experiences.

Methods:
Our data set included 420 Amish and 401 CERAD individuals. Sex-adjusted, age-adjusted, and education-adjusted Z-scores were calculated for the recall portions of the Constructional Praxis Delay (CPD) and Word List Delay (WLD). ANOVAs were then used to examine the main and interaction effects of cohort (Amish, CERAD), cognitive status (case, control), and sex on CPD and WLD Z-scores.

Results:
The Amish performed better on the CPD than the CERAD cohort. In addition, the difference between cases and controls on the CPD and WLD were smaller in the Amish and Amish female cases performed better on the WLD than the CERAD female cases.

Discussion:
The Amish performed better on the CPD task, and ADRD-related declines in CPD and WLD were less severe in the Amish. In addition, Amish females with ADRD may have preferential preservation of WLD. This study provides evidence that the Amish exhibit distinct patterns of verbal and visuospatial memory loss associated with aging and ADRD.
Mapping the context of sedentary behaviour (MAPS-B) using wearable sensors, indoor positioning systems, and diaries in older adults who are pre-frail and frail: A feasibility longitudinal study
Authors: Rodrigues Isabel B. , Swance Rachel , Tariq Suleman , Kouroukis Alexa , Adachi Jonathan , Bray Steven , Rabinovich Alexander , Ioannidis George , Zheng Rong , Kobsar Dylan , Fang Qiyin , Papaioannou Alexandra 
Published: August 2023

AbstractOlder adults who are frail are likely to be sedentary. Prior interventions to reduce sedentary time in older adults have not been successful as there is little research about the context of sedentary behaviour (posture, location, purpose, social environment). Moreover, there is limited evidence on feasible measures to assess context of sedentary behaviour in older adults. The aim of our study was to determine the feasibility of measuring context of sedentary behaviour in older adults with pre-frailty or frailty using a combination of objective and self-report measures. We defined “feasibility process”using recruitment (20 participants within two-months), retention (85%), and refusal (20%) rates and “feasibility resource” if the measures capture context and can be linked (e.g., sitting-kitchen-eating-alone) and are all participants willing to use the measures. Context was assessed using a wearable sensor to assess posture, a smart home monitoring system for location, and an electronic or hard-copy diary for purpose and social context over three days in winter and spring. We approached 80 potential individuals, and 58 expressed interest; of the 58 individuals, 37 did not enroll due to lack of interest or medical mistrust (64% refusal). We recruited 21 older adults (72±7.3 years, 13 females, 13 frail) within two months and experienced two dropouts due to medical mistrust or worsening health (90% retention). The wearable sensor, indoor positioning system, and electronic diary accurately captured one domain of context, but the hard copy was often not completed with enough detail, so it was challenging to link it to the other devices. Although not all participants were willing to use the wearable sensor, indoor positioning system, or electronic diary, we were able to triage the measures of those who did. Future studies will need to determine the most feasible and valid method to assess the context of sedentary behaviour, especially in diverse older adults.
Conformational changes in saliva proteome guides discovery of cancer aggressiveness related markers
Authors: Granato Daniela C. , Normando Ana Gabriela C. , Carnielli Carolina M. , Trino Luciana D. , Busso-Lopes Ariane F. , Câmara Guilherme A. , Filho Helder V. R. , Domingues Romênia R. , Yokoo Sami , Pauletti Bianca A. , Patroni Fabio M. , Santos-Silva Alan R. , Lopes Márcio A. , Brandão Thaís , Prado-Ribeiro Ana Carolina , de Oliveira Paulo. S. L. , Telles Guilherme P. , Paes Leme Adriana F. 
Published: August 2023

AbstractDiverse proteomics-based strategies have been applied to saliva to quantitatively identify diagnostic and prognostic targets for oral cancer. Considering that these potential diagnostic and prognostic factors may be regulated by events that do not imply variation in protein abundance levels, we investigated the hypothesis that changes in protein conformation can be associated with diagnosis and prognosis, revealing biological processes and novel targets of clinical relevance. For this, we employed limited proteolysis-mass spectrometry in saliva samples to explore structural alterations, comparing the proteome of healthy control and oral squamous cell carcinoma (OSCC) patients, with and without lymph node metastasis. Fifty-one proteins with potential structural rearrangements were associated with clinical patient features. Post-translational modifications, such as glycosylation, disulfide bond, and phosphorylation, were also investigated in our data using different search engines andin silicoanalysis indicating that they might contribute to structural rearrangements of the potential diagnostic and prognostic markers here identified. Altogether, this powerful approach allows for a deep investigation of complex biofluids, such as saliva, advancing the search for targets for oral cancer diagnosis and prognosis.Graphical AbstractOral cancer progression is associated with potential structural rearrangements.
Comparative Analysis of a Large Language Model and Machine Learning Method for Prediction of Hospitalization from Nurse Triage Notes: Implications for Machine Learning-based Resource Management
Authors: Patel Dhavalkumar , Timsina Prem , Gorenstein Larisa , Glicksberg Benjamin S , Raut Ganesh , Cheetirala Satya Narayan , Santana Fabio , Tamegue Jules , Kia Arash , Zimlichman Eyal , Levin Matthew A. , Freeman Robert , Klang Eyal 
Published: August 2023

AbstractPredicting hospitalization from nurse triage notes has significant implications in health informatics. To this end, we compared the performance of the deep-learning transformer-based model, bio-clinical-BERT, with a bag-of-words logistic regression model incorporating term frequency-inverse document frequency (BOW-LR-tf-idf). A retrospective analysis was conducted using data from 1,391,988 Emergency Department patients at the Mount Sinai Health System spanning 2017-2022. The models were trained on four hospitals’ data and externally validated on a fifth. Bio-clinical-BERT achieved higher AUCs (0.82, 0.84, and 0.85) compared to BOW-LR-tf-idf (0.81, 0.83, and 0.84) across training sets of 10,000, 100,000, and ∼1,000,000 patients respectively. Notably, both models proved effective at utilizing triage notes for prediction, despite the modest performance gap. Importantly, our findings suggest that simpler machine learning models like BOW-LR-tf-idf could serve adequately in resource-limited settings. Given the potential implications for patient care and hospital resource management, further exploration of alternative models and techniques is warranted to enhance predictive performance in this critical domain.
Inflammation causes insulin resistance via interferon regulatory factor 3 (IRF3)-mediated reduction in FAHFA levels
Authors: Yan Shuai , Santoro Anna , Niphakis Micah J. , Pinto Antonio M. , Jacobs Christopher L. , Ahmad Rasheed , Suciu Radu M. , Fonslow Bryan R. , Herbst-Graham Rachel B. , Ngo Nhi , Henry Cassandra L. , Herbst Dylan M. , Saghatelian Alan , Kahn Barbara B. , Rosen Evan D. 
Published: August 2023

AbstractObesity-induced inflammation causes metabolic dysfunction, but the mechanisms remain elusive. Here we show that the innate immune transcription factor interferon regulatory factor (IRF3) adversely affects glucose homeostasis through induction of the endogenous FAHFA hydrolase androgen induced gene 1 (AIG1) in adipocytes. Adipocyte-specific knockout of IRF3 protects mice against high-fat diet-induced insulin resistance, whereas overexpression of IRF3 or AIG1 in adipocytes promotes insulin resistance on a high-fat diet. Furthermore, pharmacological inhibition of AIG1 reversed obesity-induced insulin resistance and restored glucose homeostasis in the setting of adipocyte IRF3 overexpression. We, therefore, identify the adipocyte IRF3/AIG1 axis as a crucial link between obesity-induced inflammation and insulin resistance and suggest an approach for limiting the metabolic dysfunction accompanying obesity.
ULK1-regulated AMP sensing by AMPK and its application for the treatment of chronic kidney disease
Authors: Yanagi Tomoki , Kikuchi Hiroaki , Takeuchi Koh , Susa Koichiro , Mori Takayasu , Takahashi Naohiro , Suzuki Takefumi , Nakano Yuta , Fujiki Tamami , Hara Yu , Suzuki Soichiro , Mori Yutaro , Ando Fumiaki , Mandai Shintaro , Honda Shinya , Torii Satoru , Shimizu Shigeomi , Rai Tatemitsu , Uchida Shinichi , Sohara Eisei 
Published: August 2023

AbstractAMP-activated protein kinase (AMPK) is a central kinase involved in energy homeostasis. Increased intracellular adenosine monophosphate (AMP) levels result in AMPK activation through the binding of AMP to the γ-subunit of AMPK. Recently, we reported that AMP-induced AMPK activation is impaired in the kidneys in chronic kidney disease (CKD) despite an increase in the AMP/ATP ratio. However, the mechanisms by which AMP sensing is disrupted in CKD are unclear. In this study, we identified mechanisms of energy homeostasis in which Unc-51-like kinase 1 (ULK1)-dependent phosphorylation of AMPKγ1 at Ser260/Thr262 promotes AMP sensitivity of AMPK. AMPK activation by AMP was impaired inUlk1−/−mice despite an increased AMP/ATP ratio. We also demonstrated that MK8722, an allosteric AMPK activator, activates AMPK in the kidneys of a CKD mouse model via a pathway that is independent of AMP sensing. MK8722 treatment significantly attenuates the deterioration of renal function in CKD and is a potential therapeutic option in CKD therapeutics.
Unraveling the Interplay of Temperature Adaptation, Lipidomics, and Environmental Factors inAcinetobacter baumanniiClinical Strains
Authors: Dessenne Clara , Ménart Benoît , Acket Sébastien , Dewulf Gisèle , Guerardel Yann , Vidal Olivier , Rossez Yannick 
Published: August 2023

ABSTRACTAcinetobacter baumanniihas gained prominence due to its heightened antibiotic resistance and adaptability within healthcare settings. Unlike otherAcinetobacterspecies,A. baumanniipredominantly thrives within healthcare environments, where its persistence is underscored by physiological adaptations, including homeoviscous adaptation that modifies glycerophospholipids (GPL) to enhance membrane flexibility. The bacterium’s substantial genetic diversity highlights the paramount importance of prudent strain selection for research involving drug resistance and virulence. This study investigates the lipid composition of six clinicalA. baumanniistrains, incorporating the highly virulent model strain AB5075 with multiple antibiotic resistances. Our objective is to scrutinize the adaptations of glycerophospholipids (GPL) and glycerolipids (GL) within these isolated strains, each characterized by unique antibiotic resistance profiles, under variable temperature conditions mimicking environmental and physiological scenarios. The strains’ differential performance in motilities and biofilm formation across varying temperatures reveals intriguing patterns. Notably, the study uncovers a consistent elevation in palmitoleic acid (C16:1) content in five of the six strains at 18°C. Utilizing LC-HRMS2analysis, we elucidate shifts in GPL and GL compositions as temperatures oscillate between 18°C and 37°C for all strains. Exploration of lipid subspecies further exposes disparities in PE and PG lipids containing C16:1 and oleic acid (C18:1). This investigation not only provides insights into the physiological attributes and survival strategies ofA. baumanniibut also deepens our comprehension of its adaptive responses to temperature changes. By unraveling the dynamics of lipid composition and fatty acid profiles, this study enriches our understanding of the bacterium’s ecological fitness and behavior in diverse environments.IMPORTANCEAcinetobacter baumannii, a bacterium known for its resistance to antibiotics, is a concern in healthcare settings. This study focused on understanding how this bacterium adapts to different temperatures and how its lipid composition changes. Lipids are like the building blocks of its cell membranes. By studying these changes, scientists can gain insights into how the bacterium survives and behaves in various environments. This knowledge helps us better understand its ability to cause infections and resist treatments. The study’s findings contribute to our broader understanding of howAcinetobacter baumanniifunctions, which is important for developing strategies to combat its impact on patient health.
Structures of co-transcriptional RNA capping enzymes on paused transcription complex
Authors: Li Yan , Wang Qianmin , Xu Yanhui , Li Ze 
Published: August 2023

AbstractNascent pre-mRNA undergoes 5′ end capping as the first step of processing. Early evidences demonstrated the guanosine addition and 2′-O-ribose methylation spatiotemporally correlated with transcription machinery at the early stage of transcription. Here, we determined cryo-EM structures of PEC (paused elongation complex)-RNGTT (RNA guanylyltransferase and 5′ phosphatase) and PEC-RNGTT-CMTR1 (cap-specific mRNA (nucleoside-2′-O-)-methyltransferase). The structures show that RNGTT docks to the root of Pol II stalk through its OB fold. Within RNGTT, the OB fold binds N-terminal of triphosphatase domain and facilitates positioning its catalytic cavity facing towards the RNA exit tunnel. RNGTT dephosphorylates and guanylates PEC-bound RNAs of 17nt, 19nt, 20nt, but not 22nt, in length. CMTR1 arrayed with RNGTT on the Pol II surface through distinct interfaces. Our structures unravel that capping enzymes RNGTT and CMTR1 directly docks to paused elongation complex, and shed light on how pre-mRNA capping couples with Pol II at the specific transcription stage.
Tracking Cell Layer Contribution During Repair of the Tympanic Membrane
Authors: Dinwoodie Olivia M. , Tucker Abigail S. , Fons-Romero Juan 
Published: August 2023

AbstractThe tympanic membrane (or ear drum) is found at the interface between the middle ear and the external ear. The membrane is composed of three layers of different embryonic origin: an outer ectodermally-derived layer, a middle neural crest-derived fibroblast layer with contribution from the mesoderm-derived vasculature, and an inner endodermally-derived mucosal layer. These layers form a thin sandwich which is often perforated as a consequence of trauma, pressure changes, or middle ear inflammation. Usually, the tympanic membrane heals with minimal scarring, but in 6% of cases the perforation fails to heal leading to hearing loss, tinnitus and pain requiring surgery. How cells bridge the gap to close the perforation is an interesting question, as this needs to happen in the absence of an initial scaffold. Here we assess the contribution, timing, and interaction of the different layers of the membrane during repair in the mouse using markers and reporter mouse lines. We show that the ectodermal layer retracts after perforation, before proliferating away from the wound edge, with Keratin 5 basal cells migrating over the hole to bridge the gap. The mesenchymal and mucosal layers then use this scaffold to complete the repair, in tandem with changes in the vasculature. Finally, differentiation of the epithelium leads to formation of a scab that falls off. Our results reveal the dynamics and interconnections between the embryonic germ layers during repair and highlight how defects in healing may occur. Unearthing the complexities of TM healing is important as chronic TMP is a common clinical issue with limited treatment options.
Berberine reduce inflammation in RA rats through MCP1/CCR2 pathway
Authors: Ling Wang , Can Yu , Meng Ying Li , Man Xu , Hu Hui 
Published: August 2023

AbstractRheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovitis and systemic inflammation, leading to joint damage and functional disability. Current treatment modalities, although effective, may pose significant side effects. In this study, we investigated the anti-inflammatory properties of berberine, a natural isoquinoline alkaloid, and its potential role in ameliorating RA-associated inflammation in rats through modulation of the monocyte chemoattractant protein-1 (MCP1)/chemokine receptor 2 (CCR2) pathway. A collagen-induced arthritis (CIA) rat model was employed to mimic RA pathophysiology. Rats were treated with berberine or RS504393 for 30 days. Joint swelling, arthritis score, histopathology used to evaluate disease progression and the extent of inflammation. Immunohistochemistry and WB were used to detect the mechanism of action of berberine. Our results demonstrated that berberine treatment significantly reduced joint swelling, and inflammatory factors in CIA rats. Furthermore, berberine downregulated MCP1 and CCR2 expression, implicating the involvement of the MCP1/CCR2 signaling pathway in attenuating RA-associated inflammation. Taken together, our findings suggest that berberine may represent a promising therapeutic candidate for the management of RA and highlight the potential of targeting the MCP1/CCR2 pathway to mitigate inflammation in autoimmune diseases.