bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human follicular fluid shows diverse metabolic profiles at different follicle developmental stages
Authors: Yang Jihong , Feng Ting , Li Suying , Zhang Xinyue , Qian Yun 
Published: July 2020

Abstract
Background
To investigate the metabolic profiles in the follicular fluid (FF) samples from patients undergoing in vitro fertilization (IVF) and to analyze the correlations with follicular development.

Methods
The FF samples were obtained from participants (N = 26) who were receiving IVF under the gonadotropin-releasing hormone agonist (GnRH-a) long protocol stimulation and were collected separately from small (8–13 mm) and large (17–22 mm) follicles at the time of oocyte retrieval. Metabolomic analysis of the FF samples was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results
The results demonstrated that the size of the follicle influences the metabolic signature of the FF according to the profile and differential metabolites. Dehydroepiandrosterone (DHEA), which is enriched in steroid hormone biosynthesis, correlated negatively with the oocyte maturation rate and the high-quality embryo rate, and thus could be used to estimate the predictive diagnostic potential of follicular development.

Conclusion
The FF has different metabolic characteristics in different stages of follicular development. Exploring meaningful metabolites could predict follicular development, and modifications of these metabolites could influence follicular development.
NLRP3 inflammasome-mediated microglial pyroptosis is critically involved in the development of post-cardiac arrest brain injury
Authors: Chang Yuan , Zhu Juan , Wang Di , Li Hua , He Yihua , Liu Kewei , Wang Xiaoqiang , Peng Yuqin , Pan Suyue , Huang Kaibin 
Published: July 2020

AbstractBackgroundBrain injury is the leading cause of death and disability in survivors of cardiac arrest, where neuroinflammation is believed to play a pivotal role, but the underlying mechanism remains unclear. Pyroptosis is a pro-inflammatory form of programmed cell death that triggers inflammatory response upon infection or other stimuli. This study aims to understand the role of microglial pyroptosis in post-cardiac arrest brain injury.MethodsSprague-Dawley male rats underwent 10-min asphyxial cardiac arrest and cardiopulmonary resuscitation or sham-operation. Flow cytometry analysis, Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), co-immunoprecipitation, and immunofluorescence were used to evaluate activated microglia and CD11b-positive leukocytes after cardiac arrest and assess inflammasome activation and pyroptosis of specific cellular populations. To further explore the underlying mechanism, MCC950 or Ac-YVAD-cmk was administered to block nod-like receptor family protein 3 (NLRP3) or caspase-1, respectively.ResultsOur results showed that, in a rat model, successful resuscitation from cardiac arrest resulted in microglial pyroptosis and consequential inflammatory infiltration which was mediated by the activation of NLRP3 inflammasome. Targeting NLRP3 and caspase-1, the executor of pyroptosis, with selective inhibitors MCC950 and Ac-YVAD-cmk treatment significantly prevented microglial pyroptosis, reduced infiltration of leukocytes, improved neurologic outcome, and alleviated neuro-pathological damages after cardiac arrest in modeling rats.ConclusionsThis study demonstrates that microglial pyroptosis mediated by NLRP3 inflammasome is critically involved in the pathogenesis of post-cardiac arrest brain injury and provides a new therapeutic strategy.
Three-dimensional morphometric analysis reveals time-dependent structural changes in microglia and astrocytes in the central amygdala and hypothalamic paraventricular nucleus of heart failure rats
Authors: Althammer Ferdinand , Ferreira-Neto Hildebrando Candido , Rubaharan Myurajan , Roy Ranjan K. , Patel Atit A. , Murphy Anne , Cox Daniel N. , Stern Javier E. 
Published: July 2020

Abstract
Background
Cardiovascular diseases, including heart failure, are the most common cause of death globally. Recent studies support a high degree of comorbidity between heart failure and cognitive and mood disorders resulting in memory loss, depression, and anxiety. While neuroinflammation in the hypothalamic paraventricular nucleus contributes to autonomic and cardiovascular dysregulation in heart failure, mechanisms underlying cognitive and mood disorders in this disease remain elusive. The goal of this study was to quantitatively assess markers of neuroinflammation (glial morphology, cytokines, and A1 astrocyte markers) in the central amygdala, a critical forebrain region involved in emotion and cognition, and to determine its time course and correlation to disease severity during the progression of heart failure.

Methods
We developed and implemented a comprehensive microglial/astrocyte profiler for precise three-dimensional morphometric analysis of individual microglia and astrocytes in specific brain nuclei at different time points during the progression of heart failure. To this end, we used a well-established ischemic heart failure rat model. Morphometric studies were complemented with quantification of various pro-inflammatory cytokines and A1/A2 astrocyte markers via qPCR.

Results
We report structural remodeling of central amygdala microglia and astrocytes during heart failure that affected cell volume, surface area, filament length, and glial branches, resulting overall in somatic swelling and deramification, indicative of a change in glial state. These changes occurred in a time-dependent manner, correlated with the severity of heart failure, and were delayed compared to changes in the hypothalamic paraventricular nucleus. Morphometric changes correlated with elevated mRNA levels of pro-inflammatory cytokines and markers of reactive A1-type astrocytes in the paraventricular nucleus and central amygdala during heart failure.

Conclusion
We provide evidence that in addition to the previously described hypothalamic neuroinflammation implicated in sympathohumoral activation during heart failure, microglia, and astrocytes within the central amygdala also undergo structural remodeling indicative of glial shifts towards pro-inflammatory phenotypes. Thus, our studies suggest that neuroinflammation in the amygdala stands as a novel pathophysiological mechanism and potential therapeutic target that could be associated with emotional and cognitive deficits commonly observed at later stages during the course of heart failure.
The role of host eIF2α in viral infection
Authors: Liu Yuanzhi , Wang Mingshu , Cheng Anchun , Yang Qiao , Wu Ying , Jia Renyong , Liu Mafeng , Zhu Dekang , Chen Shun , Zhang Shaqiu , Zhao Xin-Xin , Huang Juan , Mao Sai , Ou Xumin , Gao Qun , Wang Yin , Xu Zhiwen , Chen Zhengli , Zhu Ling , Luo Qihui , Liu Yunya , Yu Yanling , Zhang Ling , Tian Bin , Pan Leichang , Rehman Mujeeb Ur , Chen Xiaoyue 
Published: July 2020

Abstract
Background
eIF2α is a regulatory node that controls protein synthesis initiation by its phosphorylation or dephosphorylation. General control nonderepressible-2 (GCN2), protein kinase R-like endoplasmic reticulum kinase (PERK), double-stranded RNA (dsRNA)-dependent protein kinase (PKR) and heme-regulated inhibitor (HRI) are four kinases that regulate eIF2α phosphorylation.

Main body
In the viral infection process, dsRNA or viral proteins produced by viral proliferation activate different eIF2α kinases, resulting in eIF2α phosphorylation, which hinders ternary tRNAMet-GTP-eIF2 complex formation and inhibits host or viral protein synthesis. The stalled messenger ribonucleoprotein (mRNP) complex aggregates under viral infection stress to form stress granules (SGs), which encapsulate viral RNA and transcription- and translation-related proteins, thereby limiting virus proliferation. However, many viruses have evolved a corresponding escape mechanism to synthesize their own proteins in the event of host protein synthesis shutdown and SG formation caused by eIF2α phosphorylation, and viruses can block the cell replication cycle through the PERK-eIF2α pathway, providing a favorable environment for their own replication. Subsequently, viruses can induce host cell autophagy or apoptosis through the eIF2α-ATF4-CHOP pathway.

Conclusions
This review summarizes the role of eIF2α in viral infection to provide a reference for studying the interactions between viruses and hosts.
Is limited aortic resection more justified in elderly patients with type A acute aortic dissection?-insights from single center experience
Authors: Qin Wei , Su Cunhua , Li Liangpeng , Carmichael Michael. , Huang Fuhua , Chen Xin 
Published: July 2020

Abstract
Background
This study compared limited aortic repair (ascending, and /or hemi-arch replacement) versus extended-arch repair (ascending, arch and proximal descending aortic replacement) used for patients aged 65 or older, who had type A acute aortic dissection (AAD), analyzing the influence of the extent of aortic repair on outcomes.

Methods
From January, 2001 to December, 2015, 103 patients aged 65 or older underwent operation due to type A AAD in Nanjing First Hospital. The cohort was divided into two subgroups according to the surgical approaches, including limited aortic replacement (LAR, n = 41) and total arch replacement + stent elephant trunk implantation (TAR+SET, n = 62).

Results
There was no significant difference in gender, age, hypertension, diabetes, smoking, PCI history, atrial fibrillation, pericardial effusion, aortic valve insufficiency (≥ moderate), shock situation before operation, and Euro-score II between the two groups except limb malperfusion and tear location. The cross-clamp time, CPB time, intubation time, ICU stay time and hospital time were all significantly less in the LAR group than in the TAR+SET group. A total of 89 patients were discharged home successfully after operation, with a difference of hospital mortality (P = 0.04). The overall survival rates at 5-year follow-up were 82.5 ± 6.0% in LAR group and 75.2 ± 5.6% in TAR+SET group, but with no difference (p = 0.151). The freedom from adverse aortic events at 5-year was 84.3 ± 6.5% in LAR group versus 97.9 ± 2.1% in TAR+SET group, with a statistical difference (p = 0.03).

Conclusion
These findings support limited aortic resection is acceptable for elderly patients with type A AAD if surgical principles allow.
Variation in KSHV prevalence between geographically proximate locations in Uganda
Authors: Nalwoga Angela , Webb Emily L. , Muserere Claudios , Chihota Belinda , Miley Wendell , Labo Nazzarena , Elliott Alison , Cose Stephen , Whitby Denise , Newton Robert 
Published: July 2020

AbstractKaposi’s sarcoma-associated herpesvirus (KSHV) transmission within endemic areas may vary. KSHV seroprevalence has been studied by different groups of researchers using different methods, making it difficult to make direct comparisons. Here we show results on KSHV seroprevalence using the same laboratory method from four different but geographically proximate populations in Uganda.Blood samples from the urban Entebbe Mother and Baby Study (EMaBS), the rural General Population Cohort (GPC), the fishing community Lake Victoria Island Intervention Study on Worms and Allergy related Diseases (LaVIISWA) and the high-risk sexual behaviour Good Health for Women Project (GHWP), were tested for IgG antibody levels to K8.1 and ORF73 recombinant proteins using ELISA.All adult participants of the EMaBS study and the GHWP were women, while the GPC (54% female) and LaVIISWA (52% female) studies had both males and females. EMaBS children were all 5 years of age while their mothers were 14 to 47 years of age. GHWP women were 15 to 45 years old, LaVIISWA participants were 1 to 72 years old while GPC participants were 1 to 103 years old. KSHV seropositivity varied in the different populations. In children aged 5 years, EMaBS had the lowest prevalence of 15% followed by GPC at 35% and LaVIISWA at 54%. In adult women, seropositivity varied from 69% (EMaBS) to 80% (LaVIISWA) to 87% (GPC) to 90% (GHWP).The reasons for the variation in prevalence are unclear but may reflect differences in the prevalence of cofactors between these four geographically proximate populations.
A novel PIEZO1 mutation in a patient with dehydrated hereditary stomatocytosis: a case report and a brief review of literature
Authors: Zama Daniele , Giulietti Giulia , Muratore Edoardo , Andolfo Immacolata , Russo Roberta , Iolascon Achille , Pession Andrea 
Published: July 2020

Abstract
Background
Dehydrated hereditary stomatocytosis (DHS) or hereditary xerocytosis is a rare, autosomal dominant hemolytic anemia characterized by macrocytosis, presence of stomatocytes and dehydration of red blood cells (RBCs). The dehydration is caused by a defect in cellular cation content. The most frequent expression of the pathology is hemolytic well-compensated anemia with high reticulocyte count, a tendency to macrocytosis, increased mean corpuscular hemoglobin concentration (MCHC) and mild jaundice. We here describe a new mutation of PIEZO1 gene, the most frequent mutated gene in DHS, in a family affected by hereditary hemolytic anemia.

Case presentation
We describe the case of a 12-years-old girl with well-compensated chronic hemolysis, increased MCHC and a father who had the same hematological characteristics. After excluding secondary causes of chronic hemolysis and enzymatic defects of the RBCs, microscopic observation of the peripheral blood smear, tests of RBC lysis, ektacytometry, SDS-PAGE and in last instance genetic analysis has been performed. This complex diagnostic workup identified a new variant in the PIEZO1 gene, never described in literature, causative of DHS. This pathogenetic variant was also detected in the father.

Conclusions
This case report highlights the importance of a correct and exhaustive diagnostic-workup in patients with clinical suspicious for hemolytic anemia in order to make a differential diagnosis. This is relevant for the management of these patients because splenectomy is contraindicated in DHS due to high thrombotic risk.
Chlorhexidine-impregnated sponge versus chlorhexidine gel dressing for short-term intravascular catheters: which one is better?
Authors: Buetti Niccolò , Ruckly Stéphane , Schwebel Carole , Mimoz Olivier , Souweine Bertrand , Lucet Jean-Christophe , Timsit Jean-François 
Published: July 2020

Abstract
Background
Chlorhexidine-gluconate (CHG) impregnated dressings may prevent catheter-related bloodstream infections (CRBSI). Chlorhexidine-impregnated sponge dressings (sponge-dress) and gel dressings (gel-dress) have never been directly compared. We used the data collected for two randomized-controlled trials to perform a comparison between sponge-dress and gel-dress.

Methods
Adult critically ill patients who required short-term central venous or arterial catheter insertion were recruited. Our main analysis included only patients with CHG-impregnated dressings. The effect of gel-dress (versus sponge-dress) on major catheter-related infections (MCRI) and CRBSI was estimated using multivariate marginal Cox models. The comparative risks of dressing disruption and contact dermatitis were evaluated using logistic mix models for clustered data. An explanatory analysis compared gel-dress with standard dressings using either CHG skin disinfection or povidone iodine skin disinfection.

Results
A total of 3483 patients and 7941 catheters were observed in 16 intensive care units. Sponge-dress and gel-dress were utilized for 1953 and 2108 catheters, respectively. After adjustment for confounders, gel-dress showed similar risk for MCRI compared to sponge-dress (HR 0.80, 95% CI 0.28–2.31, p = 0.68) and CRBSI (HR 1.13, 95% CI 0.34–3.70, p = 0.85), less dressing disruptions (OR 0.72, 95% CI 0.60–0.86, p < 0.001), and more contact dermatitis (OR 3.60, 95% CI 2.51–5.15, p < 0.01). However, gel-dress increased the risk of contact dermatitis only if CHG was used for skin antisepsis (OR 1.94, 95% CI 1.38–2.71, p < 0.01).

Conclusions
We described a similar infection risk for gel-dress and sponge-dress. Gel-dress showed fewer dressing disruptions. Concomitant use of CHG for skin disinfection and CHG-impregnated dressing may significantly increase contact dermatitis.

Trials registration
These studies were registered within ClinicalTrials.gov (numbers NCT01189682 and NCT00417235).
Treatment fidelity in the Tinnitus Retraining Therapy Trial
Authors: Scherer Roberta W. , Erdman Sue Ann , Gold Susan , Formby Craig ,   for the TRTT Research Group
Published: July 2020

Abstract
Background
Treatment fidelity, defined as ensuring that the recipient receives the intended intervention, is a critical component for accurate estimation of treatment efficacy. Ensuring fidelity and protocol adherence in behavioral trials requires careful planning during the design phase and implementation during the trial. The Tinnitus Retraining Therapy Trial (TRTT) randomized individuals with severe tinnitus to tinnitus retraining therapy (TRT, comprised of tinnitus-specific educational counseling (TC) and sound therapy (ST) using conventional sound generators (SGs)); Partial TRT (TC and placebo SGs); or standard of care (SOC), using a patient-centered care approach. Study audiologists administered both types of counseling in the TRTT, creating a challenge for managing protocol adherence.

Methods
We developed methods to enhance treatment fidelity including training, competency assessment, scripts, visual aids, and fidelity monitoring. Protocol monitors identified critical topics and content to be addressed for each type of counseling session, prepared corresponding scripts, and developed training aids and treatment-specific checklists covering those topics. Study audiologists’ competency assessment required submission and review by the protocol monitors of an audiotape of one TC and one SOC counseling session. Treatment-specific aids included scripts, a 3-D model of the ear, handouts, and for TC, an illustrated flip-chart with talking points that followed the scripted content. During the trial, audiologists completed treatment-specific checklists during each counseling session, indicating topics covered/discussed and submitted audiotapes of counseling sessions. Protocol monitors reviewed audiotapes using corresponding treatment-specific checklists. Results for individual checklist items were tabulated and proportions calculated.

Results
Twenty-five audiologists were certified for TC and/or SOC counseling and 24 completed at least one counseling session. Adherence to each of 33 critical items on the TC checklist as assessed by the protocol monitor ranged from 70 to 100% across 37 counseling sessions (median 97%), with no difference between adherence for TRT (median, 97%) and partial TRT (median, 100%). Adherence to each of 44 critical items on the SOC checklist across 30 SOC counseling sessions ranged from 42 to 100% (median, 87.5%).

Conclusion
The TRTT used multiple methods to address treatment fidelity. The close adherence to each treatment type was critical for evaluating the efficacy of the study interventions in this randomized trial.

Trial registration
clinicaltrials.gov NCT01177137. Registered on 5 August 2010.
Ddx56 maintains proliferation of mouse embryonic stem cells via ribosome assembly and interaction with the Oct4/Sox2 complex
Authors: Wang Jingwen , Liu Jiahui , Ye Miaoman , Liu Feng , Wu Su , Huang Junjiu , Shi Guang 
Published: July 2020

Abstract
Background
Embryonic stem cells (ESCs) are important source of clinical stem cells for therapy, so dissecting the functional gene regulatory network involved in their self-renewal and proliferation is an urgent task. We previously reported that Ddx56 interacts with the core transcriptional factor Oct4 by mass spectrometry analysis in ESCs. However, the exact function of Ddx56 in ESCs remains unclear.

Methods
We investigated the role of Ddx56 in mouse ESCs (mESCs) through both gain- and loss-of-function strategies. The effect of Ddx56 on mESCs was determined based on morphological changes, involvement in the network of pluripotency markers (Nanog, Oct4, Sox2), and altered lineage marker expression. In addition, the role of Ddx56 in mESCs was evaluated by polysome fractionation, qRT-PCR, and co-immunoprecipitation (co-IP). Finally, RNA sequencing was applied to explore potential network regulation by Ddx56 in mESCs.

Result
We found that Ddx56 participated in ribosome assembly, as knockout or RNAi knockdown of Ddx56 led to ribosome dysfunction and cell lethality. Surprisingly, exogenous expression of C-terminal domain truncated Ddx56 (Ddx56 ΔC-ter) did not affect ribosome assembly, but decreased mESC proliferation by downregulation of proliferation-related genes and cell cycle changing. In terms of mechanism, Ddx56 interacted with the Oct4 and Sox2 complex by binding to Sox2, whereas Ddx56 ΔC-ter showed weaker interaction with Sox2 and led to retardation of mESC proliferation.

Conclusions
Ddx56 maintains ESC proliferation by conventional regulation of ribosome assembly and interaction with the Oct4 and Sox2 complex.
A multivalent vaccine candidate targeting enterotoxigenic Escherichia coli fimbriae for broadly protecting against porcine post-weaning diarrhea
Authors: Duan Qiangde , Pang Shengmei , Wu Wenwen , Jiang Boyu , Zhang Weiping , Liu Siguo , Wang Xiaojun , Pan Zhiming , Zhu Guoqiang 
Published: July 2020

AbstractFimbriae-mediated initial adherence is the initial and critical step required for enterotoxigenicEscherichia coli(ETEC) infection. Therefore, vaccine candidates have been developed that target these fimbriae and induce specific anti-fimbriae antibodies to block initial ETEC attachment. While this vaccine effectively protects against ETEC-associated post-weaning diarrhea (PWD), developing a broadly effective vaccine against initial ETEC attachment remains a challenging problem, owing to the immunological heterogeneity among these antigens. Here, we applied multi-epitope fusion antigen (MEFA) technology to construct a FaeG–FedF–FanC–FasA–Fim41a MEFA using the adhesive subunits of predominant fimbriae K88 and F18 as the backbone, which also integrated epitopes from adhesive subunits of the rare fimbriae K99, 987P, and F41; we then generated a MEFA computational model and tested the immunogenicity of this MEFA protein in immunized mice. We next evaluated the potential of the fimbriae-targeted MEFA as a vaccine candidate to effectively prevent PWD using in vitro assessment of its anti-fimbriae, antibody-directed inhibition of bacterial adherence. Computational modeling showed that all relevant epitopes were exposed on the MEFA surface and mice subcutaneously immunized with the MEFA protein developed IgG antibodies to all five fimbriae. Moreover, anti-fimbriae antibodies induced by the MEFA protein significantly inhibited the adhesion of K88+, F18+, K99+, 987P+, and F41+ ETEC strains to piglet small intestinal IPEC-1 and IPEC-J2 cell lines. Taken together, these results indicate that FaeG–FedF–FanC–FasA–Fim41a MEFA protein induced specific anti-fimbriae neutralizing antibodies against the five targeted fimbriae. Critically, these results show the potential of fimbriae-targeted MEFA and indicate their promise as a broad, effective vaccine against PWD.