bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic inflammation in pregnant women with HIV: relationship with HIV treatment regimen and preterm delivery
Authors: Shivakoti Rupak , Giganti Mark J. , Lederman Michael M. , Ketchum Rachel , Brummel Sean , Moisi Daniela , Dadabhai Sufia , Moodley Dhayendre , Violari Avy , Chinula Lameck , Owor Maxensia , Gupta Amita , Currier Judith S. , Taha Taha E. , Fowler Mary Glenn ,   for the PROMISE study team
Published: February 2024

Objective:
HIV treatment regimen during pregnancy was associated with preterm delivery (PTD) in the PROMISE 1077 BF trial. Systemic inflammation among pregnant women with HIV could help explain differences in PTD by treatment regimen. We assessed associations between inflammation, treatment regimen, and PTD.

Design/methods:
A nested 1 : 1 case–control study (N = 362) was conducted within a multicountry randomized trial comparing three HIV regimens in pregnant women: zidovudine alone, or combination antiretroviral therapy (ART) with lopinavir/ritonavir and either zidovudine or tenofovir. Cases were women with PTD (<37 weeks of gestational age). The following inflammatory biomarkers were measured in plasma samples using immunoassays: soluble CD14 (sCD14) and sCD163, intestinal fatty acid-binding protein, interleukin (IL)-6, interferon γ, and tumor necrosis factor α. We fit regression models to assess associations between second trimester biomarkers (measured before ART initiation at 13–23 weeks of gestational age and 4 weeks later), treatment regimen, and PTD. We also assessed whether inflammation was a mediator in the relationship between ART regimen and PTD.

Results:
Persistently high interleukin-6 was associated with increased PTD. Compared with zidovudine alone, the difference in biomarker concentration between week 0 and week 4 was significantly higher (P < 0.05) for both protease inhibitor-based regimens. However, the estimated proportion of the ART effect on increased PTD mediated by persistently high biomarker levels was 5% or less for all biomarkers.

Conclusion:
Persistently high IL-6 during pregnancy was associated with PTD. Although protease inhibitor-based ART was associated with increases in inflammation, factors other than inflammation likely explain the increased PTD in ART-based regimens compared with zidovudine alone.
Brief Report: Self-Reported HIV-Positive Status but Subsequent HIV-Negative Test Results in Population-Based HIV Impact Assessment Survey Participants—11 Sub-Saharan African Countries, 2015–2018
Authors: Logan Naeemah Z. , Kilmarx Peter H. , Rolle Italia , Patel Hetal K. , Duong Yen T. , Lee Kiwon , Shang Judith D. , Bodika Stephane , Koui Isabelle T. , Balachandra Shirish , Li Michelle , Brown Kristin , Nuwagaba-Biribonwoha Harriet , Getaneh Yimam , Lulseged Sileshi , Haile Ashenafi , West Christine A. , Mengistu Yohannes , McCracken Stephen D. , Kalua Thokozania , Jahn Andreas , Kim Evelyn , Wadonda-Kabondo Nellie , Jonnalagadda Sasi , Hamunime Ndapewa , Williams Daniel B. , McOllogi Juma James , Mgomella George S. , Mdodo Rennatus , Kirungi Wilford L. , Mugisha Veronicah , Ndongmo Clement B. , Nkwemu Kennedy Chibeta , Mugurungi Owen , Rogers John H. , Saito Suzue , Stupp Paul , Justman Jessica E. , Voetsch Andrew C. , Parekh Bharat S. 
Published: February 2024

Background:
HIV testing is a critical step to accessing antiretroviral therapy (ART) because early diagnosis can facilitate earlier initiation of ART. This study presents aggregated data of individuals who self-reported being HIV-positive but subsequently tested HIV-negative during nationally representative Population-Based HIV Impact Assessment surveys conducted in 11 countries from 2015 to 2018.

Method:
Survey participants aged 15 years or older were interviewed by trained personnel using a standard questionnaire to determine HIV testing history and self-reported HIV status. Home-based HIV testing and counseling using rapid diagnostic tests with return of results were performed by survey staff according to the respective national HIV testing services algorithms on venous blood samples. Laboratory-based confirmatory HIV testing for all participants identified as HIV-positives and self-reported positives, irrespective of HIV testing results, was conducted and included Geenius HIV-1/2 and DNA polymerase chain reaction if Geenius was negative or indeterminate.

Results:
Of the 16,630 participants who self-reported as HIV-positive, 16,432 (98.6%) were confirmed as HIV-positive and 198 (1.4%) were HIV-negative by subsequent laboratory-based testing. Participants who self-reported as HIV-positive but tested HIV-negative were significantly younger than 30 years, less likely to have received ART, and less likely to have received a CD4 test compared with participants who self-reported as HIV-positive with laboratory-confirmed infection.

Conclusions:
A small proportion of self-reported HIV-positive individuals could not be confirmed as positive, which could be due to initial misdiagnosis, deliberate wrong self-report, or misunderstanding of the questionnaire. As universal ART access is expanding, it is increasingly important to ensure quality of HIV testing and confirmation of HIV diagnosis before ART initiation.
Serum Extracellular Vesicle Protein Profiling for Prediction of Corneal Transplant Rejection
Authors: Lee Hyun Ju , Bae Eun-Hye , Choi Jong Min , Kim Hyemee , Kim Hyeon Ji , Barreda Heather , Jung Sung Yun , Oh Joo Youn , Lee Ryang Hwa 
Published: February 2024

Background.
Corneal transplantation is the most common transplant procedure worldwide. Despite immune and angiogenic privilege of the cornea, 50% to 70% of corneal transplants fail in high-risk recipients, primarily because of immune rejection. Therefore, it is crucial to identify predictive biomarkers of rejection to improve transplant survival.

Methods.
In search for predictive biomarkers, we performed proteomics analysis of serum extracellular vesicles (EVs) in a fully major histocompatibility complex–mismatched (C57BL/6-to-BALB/c) murine corneal transplantation model, wherein 50% of transplants undergo rejection by day 28 following transplantation.

Results.
Our time course study revealed a decrease in the number of serum EVs on day 1, followed by a gradual increase by day 7. A comparative analysis of proteomics profiles of EVs from transplant recipients with rejection (rejectors) and without rejection (nonrejectors) found a distinct enrichment of histocompatibility 2, Q region locus 2, which is a part of major histocompatibility complex-class I of donor C57BL/6 mice, in day 7 EVs of rejectors, compared with nonrejectors, syngeneic controls, or naïve mice. In contrast, serum amyloid A2, a protein induced in response to injury, was increased in day 7 EVs of nonrejectors.

Conclusions.
Our findings offer noninvasive EV-based potential biomarkers for predicting corneal allograft rejection or tolerance.
Improved Waitlist Outcomes in Liver Transplant Patients With Mid-MELD-Na Scores Listed in Centers Receptive to Use of Organs Donated After Circulatory Death
Authors: Miyake Katsunori , Chau Lucy C. , Trudeau Sheri , Kitajima Toshihiro , Wickramaratne Niluka , Shimada Shingo , Nassar Ahmed , Gonzalez Humberto C. , Venkat Deepak , Moonka Dilip , Yoshida Atsushi , Abouljoud Marwan S. , Nagai Shunji 
Published: February 2024

Background.
Liver transplant (LT) using organs donated after circulatory death (DCD) has been increasing in the United States. We investigated whether transplant centers’ receptiveness to use of DCD organs impacted patient outcomes.

Methods.
Transplant centers were classified as very receptive (group 1), receptive (2), or less receptive (3) based on the DCD acceptance rate and DCD transplant percentage. Using organ procurement and transplantation network/UNOS registry data for 20 435 patients listed for LT from January 2020 to June 2022, we compared rates of 1-y transplant probability and waitlist mortality between groups, broken down by model for end-stage liver disease-sodium (MELD-Na) categories.

Results.
In adjusted analyses, patients in group 1 centers with MELD-Na scores 6 to 29 were significantly more likely to undergo transplant than those in group 3 (aHR range 1.51–2.11, P < 0.001). Results were similar in comparisons between groups 1 and 2 (aHR range 1.41–1.81, P < 0.001) and between groups 2 and 3 with MELD-Na 15–24 (aHR 1.19–1.20, P < 0.007). Likewise, patients with MELD-Na score 20 to 29 in group 1 centers had lower waitlist mortality than those in group 3 (scores, 20–24: aHR, 0.71, P = 0.03; score, 25–29: aHR, 0.51, P < 0.001); those in group 1 also had lower waitlist mortality compared with group 2 (scores 20–24: aHR0.69, P = 0.02; scores 25–29: aHR 0.63, P = 0.03). One-year posttransplant survival of DCD LT patients did not vary significantly compared with donation after brain dead.

Conclusions.
We conclude that transplant centers’ use of DCD livers can improve waitlist outcomes, particularly among mid-MELD-Na patients.
Differential transcriptional profiles of vagal sensory neurons in female and male mice
Authors: Jo Young-Hwan 
Published: February 2024

AbstractThe differences in metabolic homeostasis, diabetes, and obesity between males and females are evident in rodents and humans. Vagal sensory neurons in the vagus nerve ganglia innervate a variety of visceral organs and use specialized nerve endings to sense interoceptive signals. This visceral organ-brain axis plays a role in relaying interoceptive signals to higher brain centers as well as in regulating the vago-vagal reflex. I hypothesized that molecularly distinct populations of vagal sensory neurons would result in differences in metabolic homeostasis between the sexes. Single-nucleus RNA sequencing analysis of vagal sensory neurons from females and males reveals differences in the transcriptional profiles of cells in the vagus nerve ganglia. These differences are linked to the expression of sex-specific genes such asXist, Tsix, andDdx3y. Among the 13 neuronal clusters, one-fourth of the neurons in male mice are located in theDdx3y-enriched VN1 and VN8 clusters, which display a higher enrichment ofTrpv1, Piezo2, Htr3a, andVipgenes. In contrast, 70% of the neurons in females are found inXist-enriched clusters VN4, 6, 7, 10, 11, and 13, which show enriched genes such asFgfr1, Lpar1, Cpe, Esr1, Nrg1, Egfr, andOprm1. Two clusters of satellite cells are identified, one of which in males contains some oligodendrocyte precursor cells. A small population of cells expressUcp1andPlin1, indicating that they are epineural adipocytes. Understanding the physiological consequences of differences in these transcriptomic profiles on energy balance and metabolic homeostasis would help develop sex-specific treatments for obesity and metabolic dysregulation.
A multiscale model of the mammalian liver circadian clock supports synchronization of autonomous oscillations by intercellular communication
Authors: Marri Daniel , Kana Omar , Filipovic David , Sluka James P. , Liu Shengnan , Zhang Qiang , Bhattacharya Sudin 
Published: February 2024

ABSTRACTExpression of core circadian clock genes in hepatocytes across the liver lobule is temporally synchronized despite cell-autonomous oscillations in gene expression. This spatial synchronization has been attributed to an unknown intercellular coupling mechanism. Here we have developed multicellular computational models of the murine liver lobule with and without intercellular coupling to investigate the role of synchronization in circadian gene expression. Our models demonstrated that intercellular coupling was needed to generate sustained circadian oscillations with a near 24-hour period. Without coupling the simulated period was variable within the 21-28-hour range. Further model analysis revealed that a robust near-24-hour oscillation period can be generated with a wide range of circadian protein degradation rates. In contrast, only a small window of circadian gene transcription rates was able to generate realistic oscillatory periods. The coupled model accurately captured the temporal dynamics of circadian genes derived from single-nuclei transcriptomic data. Overall, this study provides novel insights into the mammalian hepatic circadian clock through modeling of spatial and temporal gene expression patterns and data-driven analysis.
Cellular mechanisms underlying beneficial versus detrimental effects of bacterial antitumor immunotherapy
Authors: Castillo Jesse Garcia , Fernandez Sebastian , Campbell Timothy , Gonzalez-Ventura Diego , Williams Jacob , Ybarra Julia , Hernandez Nicole Flores , Wells Elina , Portnoy Daniel A. , DuPage Michel 
Published: February 2024

SummaryBacteria engineered to express tumor antigens as a cancer vaccine have yielded mixed results. Here, we utilized an attenuated strain ofListeria monocytogenes(ΔactA, Lm) that does not express tumor antigen to explore the immunological response toListeriaitself in the context of intravenous (IV), intratumoral (IT), or a combination of IV+IT administration into tumor-bearing mice. Unexpectedly, we found thatLmpersisted in tumors of immune competent mice, regardless of the administration route. While ITLmalone led to the recruitment of immunosuppressive immune cells that promoted tumor growth, IVLmfollowed by ITLmcontrolled tumor growth. IVLmvaccination generated a pool of anti-Lmcytotoxic CD8 T cells that killedLm-infected non-tumor cells to control tumor growth both indirectly, by limiting cancer cell proliferation, and directly, by enhancing tumor-specific T cell responses. Our findings reveal a differential impact of ITLmadministration on tumor progression that depends on the presence of anti-LmCD8 T cells, which alone are sufficient to promote therapeutic efficacy.
The influence of talus size and shape onin vivotalocrural hopping kinematics
Authors: Behling Anja-Verena , Kelly Luke , Welte Lauren , Rainbow Michael J 
Published: February 2024

AbstractTalus implants often come in standard sizes and shapes; however, humans vary in their bone size and shape. Consequently, patient-specific implants are becoming available. Understanding how shape changes alter function in a healthy cohort may help designers determine how much specificity is required in talocrural implants.Nine participants (5 females) hopped on one leg while biplanar video radiography and force plate data were collected. 3D bone models were created from computed tomography scans. Helical axes of motion were calculated for the talus relative to the tibia (rotation axes) and a cylinder was fit through the talar dome (morphological axis). Bland-Altman plots and spatial angles tested whether the rotation and morphological axes agree. A shape model of 36 (15 females) participants was established and a cylinder fit was morphed through the range of ±3 standard deviations.The rotation and morphological axes largely agree regarding their orientation and location during hopping. The morphological axis consistently overestimates the orientation-component in anterior-posterior direction. Some shape components affect talar dome orientation and curvature independent of size. This suggests that besides size, the shape of the talar dome might affect the movement pattern during locomotion. Our findings are important to inform talocrural joint arthroplasty design.
Dysregulation of mitochondrial function by PLK1-mediated PDHA1 phosphorylation promotes Cr(VI)-associated lung cancer progression
Authors: Zhang Qiongsi , Li Zhiguo , Rao Xiongjian , Allison Derek B. , Qiao Qi , Zhang Zhuangzhuang , Kong Yifan , Zhang Yanquan , Wang Ruixin , Liu Jinghui , Wang Xinyi , Li Chaohao , Mao Fengyi , Katz Wendy , Shao Qing , Gao Tianyan , Liu Xiaoqi 
Published: February 2024

SummaryHexavalent chromium (Cr(VI)) is a class I environmental carcinogen known to induce lung epithelial cell transformation and promote lung cancer progression through alterations in the cell cycle and cellular energy metabolism. In this study, we investigated the role of polo-like kinase 1 (PLK1) in Cr(VI)-transformed (CrT) bronchial epithelial cells (BEAS-2B) and found that PLK1 expression was significantly upregulated in CrT cells, leading to impaired mitochondrial function and enhanced cell proliferation both in vitro and in vivo. High levels of PLK1 in CrT cells resulted in decreased mitochondrial activity due to defective modulation of pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1), which is crucial for pyruvate/Acetyl-CoA conversion and carbon influx into the tricarboxylic acid (TCA) cycle. Mechanistically, we demonstrated that PLK1 directly phosphorylates PDHA1 at T57, leading to E1 collapse and PDHA1 degradation via activation of mitophagy. These defects resulted in the inhibition of oxidative phosphorylation and reduction of mitochondrial superoxide generation, ultimately leading to suppression of mitochondrial-mediated apoptotic response. Our findings highlight the role of PLK1 in metabolic reprogramming during Cr(VI)-associated cancer progression, providing new insights and a potential therapeutic target to inhibit Cr(VI)-induced cancer development. Moreover, PLK1 inhibitors may also have the potential to increase chemo-sensitivity of cancer cells by restoring normal mitochondrial function, thereby mitigating drug resistance caused by mitochondrial dysfunction and hyperpolarization.
Selective deletion of interleukin-1 alpha in microglia does not modify acute outcome but regulates neurorepair processes after experimental ischemic stroke
Authors: Lemarchand Eloïse , Grayston Alba , Wong Raymond , Rogers Miyako , Ouvrier Blake , Llewellyn Benjamin , Webb Freddie , Lénárt Nikolett , Denes Adam , Brough David , Allan Stuart M , Bix Gregory J , Pinteaux Emmanuel 
Published: February 2024

AbstractInflammation is a key contributor to stroke pathogenesis and exacerbates brain damage leading to poor outcome. Interleukin-1 (IL-1) is an important regulator of post-stroke inflammation, and blocking its actions is beneficial in pre-clinical stroke models and safe in the clinical setting. However, the distinct roles of the two major IL-1 receptor type 1 agonists, IL-1α and IL-1β, and the specific role of IL-1α in ischemic stroke remain largely unknown. Here we show that IL-1α and IL-1β have different spatio-temporal expression profiles in the brain after experimental stroke, with early microglial IL-1α expression (4 h) and delayed IL-1β expression in infiltrated neutrophils and a small microglial subset (24-72 h). We examined for the first time the specific role of microglial-derived IL-1α in experimental permanent and transient ischemic stroke through microglial-specific tamoxifen-inducible Cre-loxP-mediated recombination. Microglial IL-1α deletion did not influence acute brain damage, cerebral blood flow, IL-1β expression, neutrophil infiltration, microglial nor endothelial activation after ischemic stroke. However, microglial IL-1α knock out (KO) mice showed reduced peri-infarct vessel density and reactive astrogliosis at 14 days post-stroke, alongside long-term impaired functional recovery. Our study identifies for the first time a critical role for microglial IL-1α on neurorepair and functional recovery after stroke, highlighting the importance of targeting specific IL-1 mechanisms in brain injury to develop more effective therapies.
Oleic acid triggers CD4+T cells to be metabolically rewired and poised to differentiate into proinflammatory T cell subsets upon activation
Authors: Reilly Nathalie A. , Sonnet Friederike , Dekkers Koen F. , Kwekkeboom Joanneke C. , Sinke Lucy , Hilt Stan , Suleiman Hayat M. , Hoeksema Marten A. , Mei Hailiang , van Zwet Erik W. , Everts Bart , Ioan-Facsinay Andreea , Jukema J. Wouter , Heijmans Bastiaan T. 
Published: February 2024

SummaryT cells are the most common immune cells in atherosclerotic plaques and the function of T cells can be altered by fatty acids. Here, we show that pre-exposure of CD4+T cells to oleic acid, an abundant fatty acid linked to cardiovascular events, results in a preferential differentiation into pro-inflammatory subsets upon activation by upregulating core metabolic pathways. RNA-sequencing of non-activated CD4+T cells revealed that oleic acid upregulates genes encoding enzymes responsible for cholesterol and fatty acid biosynthesis. Transcription footprint analysis linked this rewiring to the differentiation of pro-inflammatory subsets. Indeed, spectral flow cytometry showed that pre-exposure to oleic acid results in a skew toward IL-9, IL-17A, IL-5 and IL-13 producing T cells upon activation. Importantly, inhibition of either cholesterol or fatty acid biosynthesis abolishes this effect, suggesting a beneficial role for statins beyond cholesterol lowering. Taken together, fatty acids may affect inflammatory diseases by influencing T cell metabolism.
Revisiting the high-dimensional geometry of population responses in visual cortex
Authors: Pospisil Dean A. , Pillow Jonathan W. 
Published: February 2024

Recent advances in large-scale recording technology have spurred exciting new inquiries into the high-dimensional geometry of the neural code. However, characterizing this geometry from noisy neural responses, particularly in datasets with more neurons than trials, poses major statistical challenges. We address this problem by developing new tools for the accurate estimation of high-dimensional signal geometry. We apply these tools to investigate the geometry of representations in mouse primary visual cortex. Previous work has argued that these representations exhibit a power law, in which then’th principal component falls off as 1/n. Here we show that response geometry in V1 is better described by a broken power law, in which two different exponents govern the falloff of early and late modes of population activity. Our analysis reveals that later modes decay more rapidly than previously suggested, resulting in a substantially larger fraction of signal variance contained in the early modes of population activity. We examined the signal representations of the early population modes and found them to have higher fidelity than even the most reliable neurons. Intriguingly there are many population modes not captured by classic models of primary visual cortex indicating there is highly redundant yet poorly characterized tuning across neurons. Furthermore, inhibitory neurons tend to co-activate in response to stimuli that drive the early modes consistent with a role in sharpening population level tuning. Overall, our novel and broadly applicable approach overturns prior results and reveals striking structure in a population sensory representation.Significance StatementThe nervous system encodes the visual environment across millions of neurons. Such high-dimensional signals are difficult to estimate—and consequently—to characterize. We address this challenge with a novel statistical method that revises past conceptions of the complexity of encoding in primary visual cortex. We discover population encoding is dominated by approximately ten features while additional features account for much less of the representation than previously thought. Many dominant features are not explained by classic models indicating highly redundant encoding of poorly characterized nonlinear image features. Interestingly, inhibitory neurons respond in unison to dominant features consistent with a role in sharpening population representation. Overall, we discover striking properties of population visual representation with novel, broadly applicable, statistical tools.