bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated bioinformatics analysis to identify key genes and pathways involved in the endometria of patients with recurrent implantation failure undergoing in vitro fertilization and embryo transfer
Authors: Sui Yi-Lun , Li Lu , Sun Xiao-Xi 
Published: May 2023

Objectives:
Recurrent implantation failure (RIF) is a challenging clinical problem that occurs in approximately 10% of patients undergoing in vitro fertilization and embryo transfer. Because of the varied criteria for RIF, as well as differences in the time and methods of endometrial biopsy, previous studies have not reached an agreement regarding the key genes and pathways of RIF. In this study, bioinformatic analyses were performed in a homogeneous population with consistent biopsy conditions to explore the molecular mechanisms and identify key RIF-associated genes and pathways in the endometrium.

Methods:
Seven datasets from the Gene Expression Omnibus database were reviewed in detail, and GSE111974, GSE103465, and GSE26787 were included for further analysis. Common differentially expressed genes (DEGs) were identified using the GEO2R online tool. Gene Ontology and pathway enrichment analyses were performed and a protein–protein interaction (PPI) network was constructed. The RNA and protein expression files of the hub genes were obtained.

Results:
A total of 402 common DEGs were identified between patients with RIF and controls. The enrichment of these DEGs was mainly associated with tube morphogenesis, vasculature development, and positive regulation of cell migration. Pathway enrichment indicated that pathways involved in cancer, the vascular endothelial growth factor A-vascular endothelial growth factor receptor 2 signaling pathway, and cell cycle pathways were mainly involved. Moreover, a PPI network was constructed, and the three most significant submodules were mainly involved in rRNA processing and the regulation of proteolysis. The following ten DEGs with high degrees of connectivity were identified as hub genes: CDC42, VEGFA, MAP2K1, APP, CYCS, UBE2I, PLEK, LMNA, SMAD2, and ATRX.

Conclusion:
Key genes and pathways identified in this study could improve our understanding of the underlying molecular events in RIF and be used as potential biomarkers and therapeutic targets. Further studies are required to confirm these results and explore the functions of hub genes in the endometrium during the implantation window in patients with RIF.
Does Failure to Rescue Drive Race/Ethnicity-based Disparities in Survival After Heart Transplantation?
Authors: Abrahim Orit , Premkumar Akash , Kubi Boateng , Wolfe Stanley B. , Paneitz Dane C. , Singh Ruby , Thomas Jason , Michel Eriberto , Osho Asishana A. 
Published: May 2023

Objective
The objective was to assess whether race/ethnicity is an independent predictor of failure to rescue (FTR) after orthotopic heart transplantation (OHT).

Summary Background Data
Outcomes following OHT vary by patient level factors; for example, non-White patients have worse outcomes than White patients after OHT. Failure to rescue is an important factor associated with cardiac surgery outcomes, but its relationship to demographic factors is unknown.

Methods
Using the United Network for Organ Sharing database, we included all adult patients who underwent primary isolated OHT between 1/1/2006-6/30/2021. FTR was defined as the inability to prevent mortality after at least one of the UNOS-designated postoperative complications. Donor, recipient, and transplant characteristics, including complications and FTR, were compared across race/ethnicity. Logistic regression models were created to identify factors associated with complications and FTR. Kaplan Meier and adjusted Cox proportional hazards models evaluated the association between race/ethnicity and post-transplant survival.

Results
There were 33,244 adult, isolated heart transplant recipients included: the distribution of race/ethnicity was 66% (n=21,937) White, 21.2% (7,062) Black, 8.3% (2,768) Hispanic, and 3.3% (1,096) Asian. The frequency of complications and FTR differed significantly by race/ethnicity. After adjustment, Hispanic recipients were more likely to experience FTR than White recipients (OR 1.327, 95% CI[1.075-1.639], P=0.02). Black recipients had lower 5-year survival compared with other races/ethnicities (HR 1.276, 95% CI[1.207-1.348], P<0.0001).

Conclusions
In the US, Black recipients have an increased risk of mortality after OHT compared with White recipients, without associated differences in FTR. In contrast, Hispanic recipients have an increased likelihood of FTR, but no significant mortality difference compared with White recipients. These findings highlight the need for tailored approaches to addressing race/ethnicity-based health inequities in the practice of heart transplantation.
Rabbit Antithymocyte Globulin for Treatment of Corticosteroid Refractory Acute Cellular Rejection After Lung Transplantation
Authors: Rudzik Katelyn N. , Moore Cody A. , Sacha Lauren M. , Rivosecchi Ryan M. , Saul Melissa , Pilewski Joseph M. , Kilaru Silpa D. , Snyder Mark E. , McDyer John F. , Iasella Carlo J. 
Published: May 2023

Background.
Chronic lung allograft dysfunction (CLAD) remains a major cause of death after the first year posttransplant, with acute cellular rejection (ACR) being a major risk factor for CLAD. We evaluated the use of rabbit antithymocyte globulin (rATG) for corticosteroid refractory ACR in lung transplant recipients.

Methods.
We retrospectively identified 112 adult lung transplant recipients who received rATG for refractory ACR after lung transplantation. The primary endpoint was the incidence of ACR on follow-up transbronchial biopsy. Secondary endpoints included freedom from ACR within 1 y post-rATG, CLAD progression at 1 y post-rATG, and all-cause mortality at 1 y post-rATG.

Results.
A complete resolution of ACR was observed in 60.2% of patients, an improvement but not complete resolution in 22.1%, and no response on follow-up biopsy in 17.8%. Mean A grade 1 y post-rATG was 0.51 in complete responders, 1.01 in partial responders, and 2.19 in nonresponders (P < 0.001). Complete responders had significantly less new or worsening CLAD at 1 y than partial responders (17% versus 40%; P = 0.02). All-cause mortality rate was 14.9% in complete responders, 40% in partial responders, and 30% in nonresponders (P < 0.01).

Conclusions.
rATG appears to be an effective treatment of refractory ACR in lung transplant recipients. Failure to respond to rATG carries an increased risk of early CLAD and death.
Effectiveness of High-Frequency Repetitive Transcranial Magnetic Stimulation in Patients With Spinocerebellar Ataxia Type 3
Authors: Zhou Menglu , Qiu Mengqiu , Jin Yi , Li Dan , Tao Chenjuan , Lou Danning , Hu Zhouyao , Wang Yuchen , You Zhiyuan , Shao Yimeng , Zhu Yingying , Qu Mingyue , Lu Xiaodong 
Published: May 2023

Objective
To investigate the effectiveness of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on improvement of clinical symptoms in patients with spinocerebellar ataxia type 3 (SCA3).

Methods
Sixteen SCA3 participants diagnosed by genetic testing were enrolled in this sham-controlled and double-blind trial. They received either a 2-week 10-Hz rTMS intervention or sham stimulation targeting the vermis and cerebellum. The Scale for Assessment and Rating of Ataxia and the International Cooperative Ataxia Rating Scale were completed at baseline and poststimulation.

Results
Compared with baseline, the HF-rTMS group demonstrated a significant improvement in the total Scale for Assessment and Rating of Ataxia (P < 0.0001) and the International Cooperative Ataxia Rating Scale scores (P = 0.002). After 2-week treatment, the real group exhibited decreasing pattern in 3 subgroups, especially for limb kinetic function (P < 0.0001).

Conclusions
Short-term HF-rTMS treatment is a potentially promising and feasible tool for rehabilitation in patients with SCA3. Studies with long-term follow-up need to be carried out in the future and further need to assess gait, limb kinetic function, speech and oculomotor disorders.
Combined assessment ofKRASmutational status and tumor size has no impact on prognosis in early-stage non-small cell lung cancer
Authors: Eklund Ella A. , Mourad Ali , Wiel Clotilde , Sayin Sama I. , Fagman Henrik , Hallqvist Andreas , Sayin Volkan I. 
Published: May 2023

AbstractBackgroundKRASmutation status, stage and tumor size at the time of diagnosis are well-established independent prognostic factors in non-small cell lung cancer (NSCLC). Here, we investigate the prognostic value of combining survival data onKRASmutation status and tumor size in early-stage NSCLC.MethodsWe studied the combined impact ofKRASmutational status and tumor size on overall survival (OS) and risk of death in patients with stage I-II NSCLC. We performed a retrospective study including 310 consecutively diagnosed patients with early (stage I-II) NSCLCs. All consecutive patients molecularly assessed and diagnosed between 2016-2018 with stage I-II NSCLC in the Västra Götaland region of western Sweden were included in this multi-center retrospective study. The primary study outcome was OS and risk of death (hazard ratio).ResultsOut of 310 patients with stage I-II NSCLC, 37% harbored an activating mutation in theKRASgene. Our study confirmed staging and tumor size as prognostic factors. However,KRASmutational status was not found to impact OS and there was no difference in the risk of death when combiningKRASmutational status and primary tumor size.ConclusionsIn our patient cohort,KRASmutations in combination with primary tumor size are not associated with a worse prognosis in stage I-II NSCLC.
Interaction of inherited genetic variants in the NLRP3 inflammasome/IL-6 pathway with acquired clonal hematopoiesis to modulate mortality risk in patients with HFrEF
Authors: Cremer Sebastian , Katsaouni Nikoletta , Abplanalp Wesley Tyler , Berkowitsch Alexander , Kirschbaum Klara , Rieger Michael A. , Rapp Steffen , Wild Philipp S. , Dimmeler Stefanie , Schulz Marcel H. , Zeiher Andreas M. 
Published: May 2023

AbstractAimsClonal hematopoiesis (CH), defined as the presence of an expanded blood cell clone due to acquired somatic mutations in leukemia driver genes, was shown to be associated with increased mortality in patients with chronic ischemic heart failure with reduced ejection fraction (HFrEF). Mechanistically, circulating monocytes of mutation carriers display increased expression of proinflammatory genes involved in inflammasome and IL-6 signaling. Inherited genetic variants (SNP) in the IL-6 pathway are well known to affect inflammatory activation. Therefore, we investigated whether known SNPs in genes encoding for components of the inflammasome/IL-6 signaling pathway modulate fatal outcomes in HFrEF patients with CH.Methods and ResultsIn a total of 446 patients with chronic HFrEF, peripheral blood or bone marrow mononuclear cells were analyzed for the CH driver mutations DNMT3A and TET2 as well as 48 preselected SNPs affecting genes in the NLRP3 inflammasome/IL-6 signaling pathway. The 103 patients carrying a CH driver mutation demonstrated significantly increased mortality compared to the 343 patients without CH mutations (25,24% vs 13.99% at five years; p=0.0064). We identified three commonly occurring variants known to disrupt IL-6 signaling (rs2228145, rs4129267 and rs4537545), which are in strong linkage disequilibrium and present in more than 50% of CH carriers. Harboring one of those SNPs abrogated the increased mortality risk in patients with HFrEF and CH (p≤0.05 for each SNP). On the contrary, three different SNPs (rs2250417, which is associated with increased IL-18 levels; rs4722172 and rs4845625, which are known to activate IL-6 signaling) were identified to mediate fatal outcomes in patients with HFrEF and CH; p<0.05 for each). None of the assessed SNPs influenced outcomes in patients without DNMT3A or TET2 mutations. Single Cell RNA-sequencing of circulating monocytes of patients with HFrEF revealed increased inflammatory signaling in DNMT3A mutation carriers harboring IL6/IL18 activating SNPs with genes upregulated in pathways such as “cellular response to stress”, “regulation of cell activation” and “cytokine signaling in the immune system”.ConclusionAmong CH carriers with HFrEF, inherited variants in loci encoding for genes involved in inflammatory signaling interact with mortality risk. These data not only provide mechanistic insights into inflammatory mechanisms contributing to fatal outcome of HFrEF in CH carriers, but may also inform trials evaluating precision-targeted anti-inflammatory therapy in patients with DNMT3A and TET2 mutations and chronic HFrEF.
Predicting sensitivity to general anesthesia: Bispectral index versus Checkpoint-Decomposition Algorithm
Authors: Sun C. , Constant I. , Holcman D. 
Published: May 2023

AbstractDespite a large effort in EEG signal processing, classification algorithms, deep-learning approach, predicting the sensitivity to general anesthesia (GA) remains a daunting hurdle. We compare here the ability of the Bispectral Index™ (BIS™), developed more that twenty years ago to monitor the depth of anesthesia, with the real-time checkpoint-decomposition algorithm (CDA) to evaluate the patient sensitivity from the early induction phase of GA. Using EEG recorded in children anesthetised with propofol, we computed three parameters extracted from the BIS: 1-the minimum value (nadir) of the BIS, 2-the time to reach the minimum and 3-the duration spent below 40 during the first 10 minutes. Using a logistic regression procedure, we report that these parameters provide a poor prediction of sensitivity compared to the CDA, that combined the first occurrence time of iso-electric EEG traces, fraction of suppressions of theα-band and its first occurrence time. Finally, we correlate the BIS values with the maximum power frequency of theα−band, the proportion ofα−suppressions (αS) and iso-electric suppressions (IES) as well as theαandδpower ratios. To conclude, the checkpoint-decomposition algorithm complements the EEG indices such as the BIS to anticipate the sensitivity to GA.
Receipt of anti-SARS-CoV-2 pharmacotherapies among non-hospitalized U.S. Veterans with COVID-19, January 2022 to January 2023
Authors: Yan Lei , Streja Elani , Li Yuli , Rajeevan Nallakkandi , Rowneki Mazhgan , Berry Kristin , Hynes Denise M. , Cunningham Francesca , Huang Grant D. , Aslan Mihaela , Ioannou George N. , Bajema Kristina L. 
Published: May 2023

AbstractIMPORTANCESeveral pharmacotherapies have been authorized to treat non-hospitalized persons with symptomatic COVID-19. Longitudinal information on their use is needed.OBJECTIVETo analyze trends and factors related to prescription of outpatient COVID-19 pharmacotherapies within the Veterans Health Administration (VHA).DESIGN, SETTINGS, AND PARTICIPANTSThis cohort study evaluated non-hospitalized veterans in VHA care who tested positive for SARS-CoV-2 from January 2022 through January 2023, using VHA and linked Community Care and Medicare databases.EXPOSURESDemographic characteristics, regional and local systems of care including Veterans Integrated Services Networks (VISNs), underlying medical conditions, COVID-19 vaccination.MAIN OUTCOMES AND MEASURESMonthly receipt of any COVID-19 pharmacotherapy (nirmatrelvir-ritonavir, molnupiravir, sotrovimab, or bebtelovimab) was described. Multivariable logistic regression was used to identify factors independently associated with receipt of any versus no COVID-19 pharmacotherapy.RESULTSAmong 285,710 veterans (median [IQR] age, 63.1 [49.9-73.7] years; 247,358 (86.6%) male; 28,444 (10%) Hispanic; 198,863 (72.7%) White; 61,269 (22.4%) Black) who tested positive for SARS-CoV-2 between January 2022 and January 2023, the proportion receiving any pharmacotherapy increased from 3.2% (3,285/102,343) in January 2022 to 23.9% (5,180/21,688) in August 2022, and declined slightly to 20.8% (2,194/10,551) by January 2023. Across VISNs, the range in proportion of test-positive patients who received nirmatrelvir-ritonavir or molnupiravir during January 2023 was 5.9 to 21.4% and 2.1 to 11.1%, respectively. Veterans receiving any treatment were more likely to be older (adjusted odds ratio [aOR], 1.18, 95% CI 1.14-1.22 for 65 to 74 versus 50 to 64 years; aOR 1.19, 95% CI 1.15-1.23 for 75 versus 50 to 64 years), have a higher Charlson Comorbidity Index (CCI) (aOR 1.52, 95% CI 1.44-1.59 for CCI ≥6 versus 0), and be vaccinated against COVID-19 (aOR 1.25, 95% CI 1.19-1.30 for primary versus no vaccination; aOR 1.47, 95% CI 1.42-1.53 for booster versus no vaccination). Compared with White veterans, Black veterans (aOR 1.06, 95% CI 1.02 to 1.09) were more likely to receive treatment, and compared with non-Hispanic veterans, Hispanic veterans (aOR 1.06, 95% CI 1.01-1.11) were more likely to receive treatment.CONCLUSIONS AND RELEVANCEAmong veterans who tested positive for SARS-CoV-2 between January 2022 and January 2023, prescription of outpatient COVID-19 pharmacotherapies peaked in August 2022 and declined thereafter. There remain large regional differences in patterns of nirmatrelvir-ritonavir and molnupiravir use.
Impact of social dominance hierarchy on PACAP expression in the extended amygdala, corticosterone, and behavior in C57BL/6 male mice
Authors: Meloni Edward G. , Carlezon William A. , Bolshakov Vadim Y. 
Published: May 2023

AbstractThe natural alignment of animals into social dominance hierarchies produces adaptive, and potentially maladaptive, changes in the brain that influence health and behavior. Aggressive and submissive behaviors assumed by animals through dominance interactions engage stress-dependent neural and hormonal systems that have been shown to correspond with social rank. Here, we examined the impact of social dominance hierarchies established within cages of group-housed laboratory mice on expression of the stress peptide pituitary adenylate cyclase-activating polypeptide (PACAP) in areas of the extended amygdala comprising the bed nucleus of the stria terminalis (BNST) and central nucleus of the amygdala (CeA). We also quantified the impact of dominance rank on corticosterone (CORT), body weight, and behavior including rotorod and acoustic startle response. Weight-matched male C57BL/6 mice, group-housed (4/cage) starting at 3 weeks of age, were ranked as either most-dominant (Dominant), least-dominant (Submissive) or in-between rank (Intermediate) based on counts of aggressive and submissive encounters assessed at 12 weeks-old following a change in homecage conditions. We found that PACAP expression was significantly higher in the BNST, but not the CeA, of Submissive mice compared to the other two groups. CORT levels were lowest in Submissive mice and appeared to reflect a blunted response following social dominance interactions. Body weight, motor coordination, and acoustic startle were not significantly different between the groups. Together, these data reveal changes in specific neural/neuroendocrine systems that are predominant in animals of lowest social dominance rank, and implicate PACAP in brain adaptations that occur through the development of social dominance hierarchies.
A novel subset of colonocytes targeted byCitrobacter rodentiumelicits epithelial MHCII-restricted help from CD4 T cells
Authors: Zindl Carlene L. , Garrett Wilson C. , Chadha Awalpreet S. , Cai Baiyi , Harbour Stacey N. , Nagaoka-Kamata Yoshiko , Hatton Robin D. , Gao Min , Figge David A. , Weaver Casey T. 
Published: May 2023

AbstractInterleukin (IL)-22 plays a non-redundant role in immune defense of the intestinal barrier1–3. We recently discovered an indispensable role for T cells, but not ILCs, in sustaining IL-22 signaling required for protection of colonic crypts against invasion during infection by the enteropathogen,Citrobacter rodentium(C.r)4. However, identification of the intestinal epithelial cell (IEC) subsets targeted by T cell-derived IL-22 and how T cell-derived IL-22 sustains activation in IECs are undefined. Here, we identify a novel subset of absorptive IECs in the mid-distal colon that are differentially targeted byC.rand are differentially responsive to IL-22 signaling. Importantly, MHCII expression by these colonocytes was required to elicit T cell-activated IL-22 signaling necessary to resistC.rinvasion. Our findings explain the basis for the regionalization of the host response toC.rand demonstrate that epithelial cells must elicit MHCII-dependent help from IL-22–producing T cells to orchestrate immune protection in the intestines.
Mechanical Dissociation of Tissues for Single Cell Analysis Using a Simple Motorized Device
Authors: Amosu Mayowa , Gregory Andrew J. , Murtagh John D. , Pavin Nitay , Meyers Carson Taylor , Grano de Oro Fernandez Juan , Moore Kaitlyn , Maisel Katharina 
Published: May 2023

ABSTRACT/SUMMARYThe use of single cell analysis methods has grown rapidly in the last two decades and has led to rapid discoveries in cell biology and beyond. Single cell analysis requires complex systems like tissues to be dissociated, separating individual cells from extracellular tissue materials. This requires manual processing of tissues and materials through chopping, pipetting, and suspension with enzymes for degradation of the structural elements of the tissue. Manual processing can be time consuming and lead to variability between scientists. Automating this process through motorized dissociation could thus improve reproducibility of research and reduce time of cell manipulation prior to analysis. Here, we have designed a low-cost, customizable automatic tissue dissociator device that can be easily assembled by research groups for individual use. Our device allows for customizable programmed dissociation protocols for ease of use and reproducibility between researchers and can be placed into heat or cold environments based on the protocol need. We have found this device comparable in cell viability and reproducibility to manual dissociation, while significantly reducing time spent and even enhancing cells extracted from more fibrous tissues. Broad dissemination and use of this device could enhance single cell analysis reproducibility and provide a time-saving alternative to the currently used manual dissociation protocols.
Uncovering the Prevalence of Cystinosis through Genetic Analysis
Authors: Wu Chen-Han Wilfred , Tomaszewski Alicja , Stark Louisa A. , Scaglia Fernando , Elenberg Ewa , Schumacher Fredrick R. 
Published: May 2023

AbstractBackgroundCystinosis is a metabolic disease characterized by the accumulation of cystine most often presenting in an infantile nephropathic form caused by pathogenic variants in theCTNSgene. It is characterized by progressive loss of glomerular function leading to renal failure by the first decade of life, making early diagnosis crucial to improving outcomes. This study seeks to estimate the prevalence of cystinosis using a population genetics approach.MethodsThe Human Genome Mutation Database (HGMD) was used to identify known pathogenic variants inCTNS, and the 1000 Genomes (1KG) database was used to identifyCTNSvariants in a cohort representing a healthy population. These two databases were intersected to identify disease-causing variants and their carriers in the general population. The Hardy-Weinberg equilibrium was used to calculate expected carrier and affected rates for cystinosis.ResultsThe allele frequency for all disease-causing alleles was calculated to be 0.016. The predicted affected rate was calculated to be 0.00027 (approximately 1:3680), and the predicted carrier rate was 0.032 (approximately 1:30).ConclusionCompared to the reported clinical prevalence of between 1 in 100,000 to 1 in 200,000, the prevalence of cystinosis in this study was calculated to be 1 in 3,680. This significantly higher result may be due to the underdiagnosis of cystinosis or variable expressivity of variants presenting with a broad range of disease severity. These results support the proposal of newborn screening for early diagnosis and improved outcomes in infantile nephropathic cystinosis.