bluuebunny/crossref_metadata_2025_split huggingface dataset:
Under ice plankton and lipid dynamics in a subarctic lake
Authors: Kers Erwin , Leu Eva , Amundsen Per-Arne , Primicerio Raul , Kainz Martin , Poste Amanda E 
Published: May 2024

Abstract
Climate warming causes shorter winters and changes in ice and snow cover in subarctic lakes, highlighting the need to better understand under-ice ecosystem functioning. The plankton community in a subarctic, oligotrophic lake was studied throughout the ice-covered season, focusing on lipid dynamics and life history traits in two actively overwintering copepods, Cyclops scutifer and Eudiaptomus graciloides. Whereas C. scutifer was overwintering in C-IV to C-V stage, E. graciloides reproduced under ice cover. Both species had accumulated lipids prior to ice-on and showed a substantial decrease in total lipid content throughout the ice-covered period: E. graciloides (60%–38% dw) and C. scutifer (73%–33% dw). Polyunsaturated fatty acids of algal origin were highest in E. graciloides and declined strongly in both species. Stearidonic acid (18:4n-3) content in E. graciloides was particularly high and decreased rapidly during the study period by 50%, probably due to reproduction. The copepods differed in feeding behavior, with the omnivore C. scutifer continuing to accumulate lipids until January, whereas the herbivorous E. graciloides accumulated lipids from under-ice primary production during the last months of ice-cover. Our findings emphasize the importance of lipid accumulation and utilization for actively overwintering copepods irrespective of the timing of their reproduction.
Asiatic acid alleviates vascular remodeling inBAPN‐induced aortic dissection through inhibitingNF‐κBp65/CX3CL1signaling
Authors: Zhang Heng , Li Yubin , Liu Mingyuan , Guo Mingjin , Zhang Ruipeng , Zhao Kaiwen , Wu Jianlie , Zhao Zhenyuan , Zhu Hongqiao , Liu Junjun 
Published: May 2024

AbstractInflammation assumes a pivotal role in the aortic remodeling of aortic dissection (AD). Asiatic acid (AA), a triterpene compound, is recognized for its strong anti‐inflammatory properties. Yet, its effects on β‐aminopropionitrile (BAPN)‐triggered AD have not been clearly established. The objective is to determine whether AA attenuates adverse aortic remodeling in BAPN‐induced AD and clarify potential molecular mechanisms. In vitro studies, RAW264.7 cells pretreated with AA were challenged with lipopolysaccharide (LPS), and then the vascular smooth muscle cells (VSMCs)‐macrophage coculture system was established to explore intercellular interactions. To induce AD, male C57BL/6J mice at three weeks of age were administered BAPN at a dosage of 1 g/kg/d for four weeks. To decipher the mechanism underlying the effects of AA, RNA sequencing analysis was conducted, with subsequent validation of these pathways through cellular experiments. AA exhibited significant suppression of M1 macrophage polarization. In the cell coculture system, AA facilitated the transformation of VSMCs into a contractile phenotype. In the mouse model of AD, AA strikingly prevented the BAPN‐induced increases in inflammation cell infiltration and extracellular matrix degradation. Mechanistically, RNA sequencing analysis revealed a substantial upregulation of CX3CL1 expression in BAPN group but downregulation in AA‐treated group. Additionally, it was observed that the upregulation of CX3CL1 negated the beneficial impact of AA on the polarization of macrophages and the phenotypic transformation of VSMCs. Crucially, our findings revealed that AA is capable of downregulating CX3CL1 expression, accomplishing this by obstructing the nuclear translocation of NF‐κB p65. The findings indicate that AA holds promise as a prospective treatment for adverse aortic remodeling by suppressing the activity of NF‐κB p65/CX3CL1 signaling pathway.
Self-rated health and risk of incident cardiovascular events among individuals with hypertension
Authors: Kazibwe Richard , Muhammad Ahmad Imtiaz , Singleton Matthew J. , Evans Joni K. , Chevli Parag A. , Namutebi Juliana H. , Kazibwe Joseph , Epiu Isabella , German Charles , Soliman Elsayed Z. , Shapiro Michael D. , Yeboah Joseph 
Published: May 2024

Background:
The relationship between self-rated health (SRH) and cardiovascular events in individuals with hypertension, but without diabetes mellitus, is understudied.

Methods:
We performed a post hoc analysis of data from SPRINT (Systolic Blood Pressure Intervention Trial). SRH was categorized into excellent, very good, good and fair/poor. Using multivariable Cox regression, we estimated hazard ratios and 95% confidence intervals (CIs) for the association of SRH with both all-cause mortality and a composite of cardiovascular events (the primary outcome), which was defined to include myocardial infarction (MI), other acute coronary syndromes, stroke, acute decompensated heart failure, and cardiovascular death.

Results:
We included 9319 SPRINT participants (aged 67.9 ± 9 years, 35.6% women) with a median follow-up of 3.8 years. Compared with SRH of excellent, the risk [hazard ratio (95% CI)] of the primary outcome associated with very good, good, and fair/poor SRH was 1.11(0.78–1.56), 1.45 (1.03–2.05), and 1.87(1.28–2.75), respectively. Similarly, compared with SRH of excellent, the risk of all-cause mortality [hazard ratio (95% CI)] associated with very good, good, and fair/poor SRH was 1.13 (0.73–1.76), 1.72 (1.12–2.64), and 2.11 (1.32–3.38), respectively. Less favorable SRH (LF-SRH) was also associated with a higher risk of each component of the primary outcome and serious adverse events (SAE).

Conclusion:
Among individuals with hypertension, SRH is independently associated with the risk of incident cardiovascular events, all-cause mortality, and SAE. Our study suggest that guidelines should consider the potential significance of including SRH in the clinical history of patients with hypertension.
A comparative radiographic study of bone density changes around titanium implants in the posterior mandible, preoperative, and postoperative
Authors: Issa Nazih S.H. , Othman Tarafa A. , Sleman Batoul M. 
Published: May 2024

Background:
Implant success and the state of the surrounding bone require multiple measures, especially in humans, and this study aimed to identify the development of the state of the latter by means of radiographic examination performed during the period of osseointegration as well as investigate the changes in bone density that occur after implant installation and 2 months after functional loading. Implant success rates are affected by bone density at the implant site. Therefore, understanding changes in bone density after dental implant placement is essential, as it correlates with subsequent implant success.

Materials and methods:
Digital radiographs of 28 implants were taken and evaluated at four intervals: preoperatively, 1 and 3 months postoperatively, and 2 months following placement of the permanent prosthesis. Gray values were measured in different areas around the implants through analyzing X-ray images and measuring bone density around the implants using EzDent – 2D software. The aim of this study was to investigate changes in bone density around implants in three regions: apex, neck, and body, as well as to record average density values during the observation period by measuring digital image gray levels (the gray values of the digital radiographs). This was conducted to determine local bone densities in dental implant recipient sites and to study changes in local bone densities at different intervals, preoperatively and postoperatively and after placement of the prosthesis.

Results:
A decrease was observed in gray values proportional to reference values 1-month after implant insertion, but these increased at 3 months after insertion and continued to rise 2 months after placement of the prosthesis in the apical, body, and neck regions of the implant.

Conclusion:
Sensor-tuned radiography can be used as an effective method to support clinical follow-ups as well as measure changes in bone densities around implants in critical cases.
Differential expression of plasma proteins in pregnant women exposed toPlasmodium falciparummalaria
Authors: Kanoi Bernard N. , Waweru Harrison , Kobia Francis M. , Mukala Joseph , Kirira Peter , Mogere Dominic , Gallini Radiosa , Åberg Mikael , Vatish Manu , Gitaka Jesse , Kamali-Moghaddam Masood 
Published: May 2024

AbstractIn sub-Saharan Africa, pregnant women are at greater risk of malaria infection than non-pregnant adult women. The infection may lead to pregnancy-associated malaria (PAM) because of the sequestration ofPlasmodium falciparum-infected erythrocytes in the placental intervillous space. Although there are several tools for diagnosing malaria infection during pregnancy, including blood smear microscopic examination, rapid diagnostic tests, and PCR, there are no tools for detecting placental infection and, by extension, any dysfunction associated with PAM. Thus, PAM, specifically placental infection, can only be confirmed via postnatal placental histopathology. Therefore, there is an urgent need for specific serum biomarkers of PAM. Here, we used the high throughput proximity extension assay to screen plasma from malaria-exposed pregnant women for differentially expressed proteins that can predict PAM or adverse malaria outcomes. Such biomarkers may also elucidate the pathophysiology of PAM. We observed that the IgG Fc receptor IIb (Uniprot ID P31994) and HO-1 (P09601) are consistently highly expressed in malaria-positive samples compared to samples from malaria-negative pregnant women. On the contrary, NRTN (Q99748) and IL-20 (Q9NYY1) were differentially expressed in the malaria-negative women. IL-20 exhibited the highest discriminatory power (AUC = 0.815), indicating a strong association with malaria status. These proteins should be considered for further evaluation as biomarkers of malaria-induced placental dysfunction in pregnant women.
Genome-wide Mendelian Randomization Identifies Potential Drug Targets for Dorsopathies
Authors: Cui Yu , Guo Jiarui , Lu Yuanxi , Hu Mengting , Zhou He , Zhang Wancong , Tang Shijie 
Published: May 2024

AbstractBackgroundDorsopathies are a group of musculoskeletal disorders affecting the spinal column and related structures, contributing significantly to global disability rates and healthcare costs. Despite their prevalence, the genetic and biological mechanisms underlying dorsopathies are not fully understood.MethodSummary-data-based Mendelian Randomization (SMR) and colocalization analysis were employed, using data from genome-wide association studies (GWAS) and cis-expression quantitative trait loci (cis-eQTLs) databases. Genes with a colocalization posterior probability (PP.H4) above 0.7 in SMR results were selected for additional analysis. These selected genes underwent MR analysis to examine possible causal connections with dorsopathies, and sensitivity analyses were carried out to ensure robustness. Additionally, two transcriptome-wide association studies (TWAS) were utilized to confirm and screen for potential drug targets.ResultWe identified four essential genes linked to dorsopathies:NLRC4,CGREF1,KHK, andRNF212. Mendelian randomization (MR) analysis revealed a potential causal link between these genes and dorsopathies. Elevated transcription levels ofNLRC4,CGREF1, andKHKcorrelated with reduced dorsopathies risk, while increased levels ofRNF212were associated with heightened risk of dorsopathies. Regarding methylation sites, an increase incg04686953fully mediated the decreased risk of dorsopathies byRNF212. Similarly, the risk effect ofcg26638505andcg18948125was entirely mediated byNLRC4, whileCGREF1predominantly mediated the risk-increasing effect ofcg06112415and the decrease effect ofcg22740783.ConclusionDorsopathies were associated with four pivotal genes:NLRC4,CGREF1,KHK, andRNF212. Methylation analysis identified cg04686953 andcg22740783as protective against dorsopathies risk, whilecg26638505,cg18948125, andcg06112415exhibited a risk-increasing impact.
Enhanced Detection and Genotyping of Disease-Associated Tandem Repeats Using HMMSTR and Targeted Long-Read Sequencing
Authors: Van Deynze Kinsey , Mumm Camille , Maltby Connor J. , Switzenberg Jessica A. , Todd Peter K. , Boyle Alan P. 
Published: May 2024

AbstractTandem repeat sequences comprise approximately 8% of the human genome and are linked to more than 50 neurodegenerative disorders. Accurate characterization of disease-associated repeat loci remains resource intensive and often lacks high resolution genotype calls. We introduce a multiplexed, targeted nanopore sequencing panel and HMMSTR, a sequence-based tandem repeat copy number caller. HMMSTR outperforms current signal- and sequence-based callers relative to two assemblies and we show it performs with high accuracy in heterozygous regions and at low read coverage. The flexible panel allows us to capture disease associated regions at an average coverage of >150x. Using these tools, we successfully characterize known or suspected repeat expansions in patient derived samples. In these samples we also identify unexpected expanded alleles at tandem repeat loci not previously associated with the underlying diagnosis. This genotyping approach for tandem repeat expansions is scalable, simple, flexible, and accurate, offering significant potential for diagnostic applications and investigation of expansion co-occurrence in neurodegenerative disorders.Abstract Figure
Investigating the Impact of Segregation and Integration on Infection Dynamics: Analysis of a Cholera Model in a Two-Population System
Authors: El Deeb Omar , Matar Antoine 
Published: May 2024

AbstractWe present a novel dynamic model designed to depict Cholera outbreaks within a two-population framework featuring two environmental reservoirs. The model is designed to emulate the impact of segregation or integration between two populations on the transmission of the disease and infections throughout the entire community, both with and without non-medicinal interventions. This is achieved by allowing infectious individuals to interact with the reservoir of the alternate population at different levels of suppression, in addition to their regular interaction with their own reservoir.We find out that increased suppression of cross community interaction reduces the number of infections in the overall population as well as in the population with less contamination and contact. Additionally, we predict significant delays in the occurrence of peak infections, affording public health authorities crucial time for intervention. Lowering cross-immunity interactions also leads to a decrease in bacterial concentrations in environmental reservoirs. Finally, we demonstrate that non-medicinal interventions, including sanitation and water purification, would significantly reduce and delay infections, providing a valuable time frame for implementing additional medicinal measures.
Genome-wide study of gene-by-sex interactions identifies risks for cleft palate
Authors: Robinson Kelsey , Parrish Randy , Adeyemo Wasiu Lanre , Beaty Terri H. , Butali Azeez , Buxó Carmen J. , Gowans Lord JJ , Hecht Jacqueline T. , Moreno Lina , Murray Jeffrey C. , Shaw Gary M. , Weinberg Seth M. , Brand Harrison , Marazita Mary L. , Cutler David J. , Epstein Michael P. , Yang Jingjing , Leslie Elizabeth J. 
Published: May 2024

AbstractStructural birth defects affect 3-4% of all live births and, depending on the type, tend to manifest in a sex-biased manner. Orofacial clefts (OFCs) are the most common craniofacial structural birth defects and are often divided into cleft lip with or without cleft palate (CL/P) and cleft palate only (CP). Previous studies have found sex-specific risks for CL/P, but these risks have yet to be evaluated in CP. CL/P is more common in males and CP is more frequently observed in females, so we hypothesized there would also be sex-specific differences for CP. Using a trio-based cohort, we performed sex-stratified genome-wide association studies (GWAS) based on proband sex followed by a genome-wide gene-by-sex (GxS) interaction testing. There were 13 loci significant for GxS interactions, with the top finding inLTBP1(RR=3.37 [2.04 - 5.56], p=1.93x10-6). LTBP1 plays a role in regulating TGF-B bioavailability, and knockdown in both mice and zebrafish lead to craniofacial anomalies. Further, there is evidence for differential expression ofLTBP1between males and females in both mice and humans. Therefore, we tested the association between the imputed genetically regulated gene expression of genes with significant GxS interactions and the CP phenotype. We found significant association forLTBP1in cell cultured fibroblasts in female probands (p=0.0013) but not in males. Taken altogether, we show there are sex-specific risks for CP that are otherwise undetectable in a combined sex cohort, andLTBP1is a candidate risk gene, particularly in females.
Treatment of Spontaneous Subarachnoid Hemorrhage: A 20-year National Inpatient Sample Review
Authors: Feler Joshua , Wolman Dylan , Torabi Radmehr , Chen Jia-Shu , Teshome Abigail , Sastry Rahul , Doberstein Curtis , Jayaraman Mahesh , Moldovan Krisztina , Mahta Ali 
Published: May 2024

AbstractBackgroundAneurysmal subarachnoid hemorrhage is a major source of morbidity and mortality, and its management has undergone foundational changes over the last 2 decades. We reviewed the National Inpatient Sample (NIS) to outline the changes in severity of illness, surgical management, and patient outcomes over time.MethodsA retrospective cohort of admissions for spontaneous subarachnoid hemorrhage (SAH) in the NIS from 2001-2020 was reviewed, including those that underwent microsurgical or endovascular surgery to secure a ruptured aneurysm. National incidence was calculated, and multivariable regression was used to identify changes in incidence and outcome through time, segmented by epoch.ResultsReview of the NIS identified 450,723 SAH patients, of which 182,151 underwent surgical aneurysm treatment. The incidence of spontaneous SAH fell −0.127 per 100,000 person-years each year [95%CI: −0.164, −0.0887]). Among patients surgically treated for aneurysmal SAH, the proportion of patients <50 years old fell from 40% to 30% between first and final epochs, and the proportion of those in the lowest stroke scale category, roughly equivalent to Hunt & Hess grade 1 or 2, fell from 68% to 49%. The proportion treated by microsurgery fell from 70% to 23% in favor of endovascular surgery. Hospital mortality among these treated cases was stable at 13% throughout the study period despite increasing illness severity indices. After adjustment, there was a 41% reduction of odds of hospital mortality in the final epoch compared with the first.ConclusionsThe incidence of hospitalization for spontaneous SAH fell between 2001 and 2020. Patients undergoing surgery to secure an aneurysm were more severely ill through time yet experienced a stable hospital mortality rate.
An shRNA screen in primary human beta cells identifies the serotonin 1F receptor as a negative regulator of survival during transplant
Authors: Lee Rebecca A. , Chopra Deeksha G. , Nguyen Vinh , Huang Xi-Ping , Zhang Yaohuan , Shariati Kaavian , Yiv Nicholas , Schugar Rebecca , Annes Justin , Roth Bryan , Ku Gregory M. 
Published: May 2024

AbstractIslet transplantation can cure type 1 diabetes, but peri-transplant beta cell death limits this procedure to those with low insulin requirements. Improving human beta cell survival or proliferation may make islet transplantation a possibility for more type 1 patients. To identify novel regulators of beta cell survival and proliferation, we conducted a pooled small hairpin RNA (shRNA) screen in primary human beta cells transplanted into immunocompromised mice. shRNAs targeting several cyclin dependent kinase inhibitors were enriched after transplant. Here, we focused on the Gi/o-coupled GPCR, serotonin 1F receptor (HTR1F,5-HT1F) which our screen identified as a negative regulator of beta cell numbers after transplant.In vitro, 5-HT1Fknockdown induced human beta cell proliferation but only when combined with harmine and exendin-4.In vivo, knockdown of 5-HT1Freduced beta cell death during transplant. To demonstrate the feasibility of targeting 5-HT1Fin islet transplant, we identified and validated a small molecule 5-HT1Fantagonist. This antagonist increased glucose stimulated insulin secretion from primary human islets and cAMP accumulation in primary human beta cells. Finally, the 5-HT1Fantagonist improved glycemia in marginal mass, human islet transplants into immunocompromised mice. We identify 5-HT1Fas a novel druggable target to improve human beta cell survival in the setting of islet transplantation.One Sentence SummarySerotonin 1F receptor (5-HT1F) negatively regulates insulin secretion and beta cell survival during transplant.
Identification and Expression Analysis of CDPK Family inEriobotrya japonica, revealsEjCDPK25in Response to Freezing Stress in Fruitlets
Authors: Xiong Yifan , Lin Shunquan , Wu Jincheng , Lin Shoukai 
Published: May 2024

AbstractThe fruitlets of loquat (Eriobotrya japonicaLindl.) are susceptible to freezing injury due to their developmental cycle encountering winter. Freezing stress severely damages the fruitlets, resulting in loss of fruit yield and quality. Studies have shown that Ca2+, as a second messenger, is involved in signal transduction in loquat fruitlets under freezing stress. However, the mechanism of downstream calcium signal transduction in loquat fruitlets under freezing stress is currently unclear. Calcium-depend protein kinase (CDPK) as the most particular calcium sensor family in plants, play an important role in multiple stress signal transduction including freezing. In this study, we identified the loquat CDPK family on a genome-wide scale. A total of 34EjCDPKgenes were identified and studied for basic structural and phylogenetic features. EjCDPKs can be divided into four subgroups phylogenetically. The patterns of exon-intron and protein motif are highly conserved among the subgroups. Collinearity analysis identified several segmental duplicate events in EjCDPK family. RNA-seq based transcription analysis indicated that partial ofEjCDPKs differently expressed in response to freezing stress with tissue-specific. Moreover, we preformed correlation analysis between expression value and trait data of loquat fruitlet under freezing stress by weighted co-expression gene network. After that,EjCDPK25was selected as the candidate because of its potential freezing stress response function. Protein kinase related GO terms were enriched inEjCDPK25co-expression genes, and then QPCR was performed to examine the target gene’s expression pattern. In addition,EjCDPK25was cloned to construct overexpression vector to obtain transgenicArabidopsisplants. Transgenic and wild-typeArabidopsiswere suffered freezing stress treatments (-5°C). The results showed that the survival rate ofEjCDPK25overexpressing transgenicArabidopsiswas significantly higher than WT. In summary, this study identified loquat CDPK family firstly, and our data provide significant insights into the evolution and function of loquat CDPKs. Above all, a freezing stress response geneEjCDPK25was verified can increase the resistance of freezing stress inArabidopsis.