bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of novel key genes and potential candidate small molecule drugs in diabetic kidney disease using comprehensive bioinformatics analysis
Authors: Li Bin , Ye Siyang , Fan Yuting , Lin Yi , Li Suchun , Peng Huajing , Diao Hui , Chen Wei 
Published: August 2022

Objective: The currently established diagnostic and prognostic tools for diabetic kidney disease (DKD) have limitations, which demands the necessity to find new genes and pathways associated with diagnosis and treatment. Our study aims to reveal the gene expression alteration and discover critical genes involved in the development of DKD, thus providing novel diagnostic molecular markers and therapeutic targets.Materials and methods: The differences of infiltrating immune cells within kidney were compared between healthy living donors and DKD patients. Besides, differentially expressed genes (DEGs) within kidney from healthy living donor, early stage DKD and advanced stage DKD samples were detected. Furthermore, the weighted co-expressed network (WGCNA) and protein-protein interaction (PPI) network were constructed, followed by recognition of core hub genes and module analysis. Receiver operating characteristic (ROC) curve analysis was implemented to determine the diagnostic value of hub genes, correlation analysis was employed to explore the association between hub genes and infiltrating immune cells, and certain hub genes was validated by quantitative real-time PCR and immunohistochemistry staining in cultured tubule cells and diabetic mice kidney. Finally, the candidate small molecules as potential drugs to treat DKD were anticipated through utilizing virtual screening and molecular docking investigation.Results: Our study revealed significantly higher proportion of infiltrating immune cells within kidney from DKD patients via probing the immune landscape by single-cell transcriptomics. Besides, 126 commonly shared DEGs identified among three group samples were enriched in immune biological process. In addition, the ROC curve analysis demonstrated the strong diagnostic accuracy of recognized hub genes (NFKB1, DYRK2, ATAD2, YAP1, and CHD3) from PPI network. Correlation analysis further confirmed the positive association between these hub genes with infiltrating natural killer cells. More importantly, the mRNA transcripts and protein abundance of YAP1 were significantly higher in high glucose-treated renal tubule cells and diabetic mice kidney, and the small molecules exhibiting the best binding affinities with YAP1 were predicted and acquired.Conclusion: Our findings for the first time indicate that NFKB1, DYRK2, ATAD2, YAP1, and CHD3 might be potential novel biomarkers and therapeutic targets for DKD, providing insights into the molecular mechanisms underlying the pathogenesis of DKD.
Novel genetic associations with five aesthetic facial traits: A genome-wide association study in the Chinese population
Authors: Wang Peiqi , Sun Xinghan , Miao Qiang , Mi Hao , Cao Minyuan , Zhao Shan , Wang Yiyi , Shu Yang , Li Wei , Xu Heng , Bai Ding , Zhang Yan 
Published: August 2022

Background: The aesthetic facial traits are closely related to life quality and strongly influenced by genetic factors, but the genetic predispositions in the Chinese population remain poorly understood.Methods: A genome-wide association studies (GWAS) and subsequent validations were performed in 26,806 Chinese on five facial traits: widow’s peak, unibrow, double eyelid, earlobe attachment, and freckles. Functional annotation was performed based on the expression quantitative trait loci (eQTL) variants, genome-wide polygenic scores (GPSs) were developed to represent the combined polygenic effects, and single nucleotide polymorphism (SNP) heritability was presented to evaluate the contributions of the variants.Results: In total, 21 genetic associations were identified, of which ten were novel: GMDS-AS1 (rs4959669, p = 1.29 × 10−49) and SPRED2 (rs13423753, p = 2.99 × 10−14) for widow’s peak, a previously unreported trait; FARSB (rs36015125, p = 1.96 × 10−21) for unibrow; KIF26B (rs7549180, p = 2.41 × 10−15), CASC2 (rs79852633, p = 4.78 × 10−11), RPGRIP1L (rs6499632, p = 9.15 × 10−11), and PAX1 (rs147581439, p = 3.07 × 10−8) for double eyelid; ZFHX3 (rs74030209, p = 9.77 × 10−14) and LINC01107 (rs10211400, p = 6.25 × 10−10) for earlobe attachment; and SPATA33 (rs35415928, p = 1.08 × 10−8) for freckles. Functionally, seven identified SNPs tag the missense variants and six may function as eQTLs. The combined polygenic effect of the associations was represented by GPSs and contributions of the variants were evaluated using SNP heritability.Conclusion: These identifications may facilitate a better understanding of the genetic basis of features in the Chinese population and hopefully inspire further genetic research on facial development.
Women and adaptive capacity to climate change in East African seascapes – Zanzibar as an example
Authors: de la Torre-Castro Maricela , Lindström Lars , Jiddawi Narriman S. , Pike Felicity , Max Astrid 
Published: August 2022

As the climate crisis persists, there is a crucial need to increase knowledge on adaptive capacity and the underlying factors building it. This is particularly important for disadvantaged groups, such as coastal women in East Africa. Women’s livelihoods in these seascapes are and will be more severely affected by climate change and the capacity of East African states to deal with these challenges is limited in terms of financial and human capital. In this research, we investigated the underlying factors building the adaptive capacity of coastal women in Zanzibar (Unguja Island), Tanzania. Coastal women (N=117) were interviewed in villages around the island to gather information about potential factors supporting adaptive capacity. This was analysed applying Cinner et al (2018) five domains typology for adaptive capacity, i.e. assets, flexibility, organizations, learning and agency. The results show that women had relatively low adaptive capacity, extended poverty and very high dependence on seaweed farming of red algae, a livelihood providing low income and already being seriously affected by climate variability and change. Women’s observations of key variables related to environmental changes corresponded to most scientific findings. It was, however, unclear how that knowledge is useful and enhances adaptive capacity. Adaptive capacity was generally low but individual differences were found in which ten women had a high income. The results show that the factors underlying adaptive capacity are complex and interact with each other, being positive, negative and unclear. Many of the identified factors deserve future research. This study adds to the pool of knowledge by addressing women (not only men); coastal ecosystems (as land and freshwater systems are more studied) and the individual level (since most studies focus on national and community levels). The study illustrates that institutional renewal, bridging and cooperation is possible in Zanzibar bringing good news to the region.
Postoperative day 1 serum cystatin C level predicts postoperative delayed graft function after kidney transplantation
Authors: Li Yajuan , Wang Bo , Wang Le , Shi Kewei , Zhao Wangcheng , Gao Sai , Chen Jiayu , Ding Chenguang , Du Junkai , Gao Wei 
Published: August 2022

BackgroundDelayed graft function (DGF) commonly occurs after kidney transplantation, but no clinical predictors for guiding post-transplant management are available.Materials and methodsData including demographics, surgery, anesthesia, postoperative day 1 serum cystatin C (S-CysC) level, kidney functions, and postoperative complications in 603 kidney transplant recipients who met the enrollment criteria from January 2017 to December 2018 were collected and analyzed to form the Intention-To-Treat (ITT) set. All perioperative data were screened using the least absolute shrinkage and selection operator. The discrimination, calibration, and clinical effectiveness of the predictor were verified with area under curve (AUC), calibration plot, clinical decision curve, and impact curve. The predictor was trained in Per-Protocol set, validated in the ITT set, and its stability was further tested in the bootstrap resample data.ResultPatients with DGF had significantly higher postoperative day 1 S-CysC level (4.2 ± 1.2 vs. 2.8 ± 0.9 mg/L; P &lt; 0.001), serum creatinine level (821.1 ± 301.7 vs. 554.3 ± 223.2 μmol/L; P &lt; 0.001) and dialysis postoperative (74 [82.2%] vs. 25 [5.9%]; P &lt; 0.001) compared with patients without DGF. Among 41 potential predictors, S-CysC was the most effective in the parsimonious model, and its diagnostic cut-off value was 3.80 mg/L with the risk score (OR, 13.45; 95% CI, 8.02–22.57; P &lt; 0.001). Its specificity and sensitivity indicated by AUC was 0.832 (95% CI, 0.779–0.884; P &lt; 0.001) with well fit calibration. S-CysC yielded up to 50% of clinical benefit rate with 1:4 of cost/benefit ratio.ConclusionThe postoperative day 1 S-CysC level predicts DGF and may be used as a predictor of DGF but warrants further study.
Intralipid fails to rescue bupivacaine-induced cardiotoxicity in late-pregnant rats
Authors: Sherman Caitlin , Koons Natalie , Zargari Michael , Cha Catherine , Hirsch Jason , Hong Richard , Eghbali Mansoureh , Umar Soban 
Published: August 2022

BackgroundFemales routinely receive bupivacaine for obstetric and regional anesthesia. An accidental overdose of bupivacaine can result in cardiotoxicity and cardiac arrest. Intralipid (ILP) rescues bupivacaine-induced cardiotoxicity in male rats. However, bupivacaine cardiotoxicity and ILP rescue have not been studied in non-pregnant and late-pregnant female rats. Here, we tested the hypothesis that an appropriate dose of ILP would rescue non-pregnant and late-pregnant rats from bupivacaine-induced cardiotoxicity.MethodsNon-pregnant (n = 6) and late-pregnant (n = 7) female rats received intravenous bupivacaine (10-mg/kg bolus) to induce asystole. Resuscitation with 20% ILP (5-ml/kg actual body weight, single bolus, and 0.5-ml/kg/min maintenance) and chest compressions were continued for 10-min. Serial heart rate (HR), left ventricular ejection-fraction (LVEF%), and LV-fractional shortening (LVFS%) were recorded at baseline and 10-min after bupivacaine-induced cardiac arrest. Data are mean ± SD followed by 95% CI. P-values &lt; 0.05 were considered statistically significant.ResultsAll rats developed cardiac arrest within a few seconds after bupivacaine. All non-pregnant rats were successfully rescued by ILP, with a HR of 280 ± 32 bpm at baseline vs. 212 ± 18 bpm at 10-min post ILP (p &lt; 0.01), LVEF of 70 ± 6% vs. 68 ± 5% (p = ns), and LVFS of 41 ± 5% vs. 39 ± 4% (p = ns). Interestingly, 6 out of 7 late-pregnant rats did not recover with ILP. Baseline HR, LVEF and LVFS for late-pregnant rats were 330 ± 40 bpm, 66 ± 5% and 38 ± 4%, respectively. At 10-min post ILP, the HR, LVEF, and LVFS were 39 ± 102 bpm (p &lt; 0.0001), 8 ± 22% (p &lt; 0.0001), and 5 ± 12% (p &lt; 0.001), respectively.ConclusionsILP successfully rescued bupivacaine-induced cardiac arrest in non-pregnant rats, but failed to rescue late-pregnant rats.
Dupilumab modulates specific IgE mite responses at the molecular level in severe T2-high atopic dermatitis: A real-world experience
Authors: González-Pérez Ruperto , Poza-Guedes Paloma , Mederos-Luis Elena , Sánchez-Machín Inmaculada 
Published: August 2022

BackgroundAtopic dermatitis (AD) is regarded as a chronic systemic disease which is characterized by a robust overexpression of type 2 related cytokines, with increased total IgE levels and a concomitant sensitization to common allergens. Dupilumab, a fully human monoclonal antibody (mAb) to IL-4Rα that inhibits both IL-4 and IL-13 signaling, has previously shown a marked and rapid improvement when treating the moderate-to-severe forms of AD. We sought to evaluate the real-world evidence (RWE) of dupilumab in the modulation of total and specific IgE (sIgE) serum levels to a panel of molecular house dust mites (HDM) and storage mites (SM) allergens in patients with severe AD.MethodsDemographic and clinical data for severe AD adult patients receiving dupilumab treatment (300 mg every 2 weeks) were reviewed. Mean (standard deviations SD) values and percent changes from baseline in total and sIgE to the complete HDM and SM extracts, and 14 individual molecular allergens were measured over 52 weeks.ResultsSignificant (p &lt; 0.05) changes in mean total IgE levels were observed from baseline to week-52 after treatment with dupilumab. Despite no changes were found in sIgE against the extract of HDM during the 52-week treatment with dupilumab, baseline mean levels from 7 out of 14 individual molecular mite allergens -Der p 1, Der p 2, Der p 5, Der p 7, Der p 21, Der p 23, and Lep d 2- were significantly (p &lt; 0.05) decreased—after 52 weeks of treatment with dupilumab.ConclusionsDupilumab therapy for 52 weeks resulted in a profound reduction in blood levels of total IgE and allergen-specific IgE to both HDM and SM at the molecular level in adults with severe AD under RWE conditions. The potential benefits of these concomitant immunomodulatory effects after treatment with dupilumab should be explored to a greater extent.
Frailty index, mortality, and length of stay in a geriatric short-stay unit in Guadeloupe
Authors: Vainqueur Larissa , Simo-Tabue Nadine , Villeneuve Roxane , Dagonia Dorice , Bhakkan-Mambir Bernard , Mounsamy Ludwig , Delacroix Vaynome , Tabue-Teguo Maturin 
Published: August 2022

ContextThe COVID-19 pandemic has placed a tremendous stress on healthcare systems and caused reorganization. As the pandemic intensifies, identifying the profile of patients with COVID-19 was primordial in order to predict negative outcomes and organize healthcare resources. Age is associated with COVID-19’s mortality, but for obvious ethical reasons, chronological age cannot be the sole criterion for predicting negative outcomes.ObjectiveThe objective of this study was to determine the relationship between frailty index (FI) and length of hospital stay, and death in a non-COVID population of patients aged 75 years old and above.Methods and designA retrospective, analytical, single-centered observational study was performed in the geriatric short-stay accommodation unit at Guadeloupe University Hospital. For this study, 158 patients who were at least 75 years old were recruited from November 2020 to May 2021. FI was calculated as the number of deficits in a participant divided by the total number of deficits considered (the cut-off of FI is.25 in outpatient). Multivariate logistics regression analyses were conducted to assess the association between frailty and death, and length of stay.ResultsThe average age of the participants was 85.7 ± 6.74 with a range of 75–104. Twenty-four of the patients died during hospitalization. FI was only significantly associated with mortality even after adjustment for age and gender (HR 26.3, 95% CI 1.7–413.4, P = 0.021). The association was stronger in the highest tertile of the FI (age- and gender-adjusted HR 4.6, 95% CI 1.39–15.11, P = 0.01). There was no significant interaction between FI and length of stay.ConclusionOur study shows an association between FI (in terms of age-related deficit accumulation) and mortality in a non-COVID geriatric short-stay unit in Guadeloupe. The FI seems to have a lower capacity to catch events such as length of stay in this very complex population. Further research studies have to be conducted for better understanding and investigation of our findings.
Variable effects of omaveloxolone (RTA408) on primary fibroblasts with mitochondrial defects
Authors: Zighan Madleen , Arkadir David , Douiev Liza , Keller Guy , Miller Chaya , Saada Ann 
Published: August 2022

Omaveloxolone (RTA408) is a second-generation oleanane triterpenoid Nrf2 inducer with antioxidant and anti-inflammatory properties and was reported to improve mitochondrial bioenergetics. It is currently being tested in medical trials for Friedrich ataxia, a genetic, multi-organ disease involving mitochondrial dysfunction. Thus, omaveloxolone could potentially be beneficial for additional disorders involving mitochondrial dysfunction. To this end, we investigated its effect on primary fibroblasts derived from patients with mitochondrial complex I deficiency, mitochondrial cytochrome oxidase deficiency, and two recessive forms of Parkinson’s disease. Patients and control cells were incubated in the presence or absence of 50 nM omaveloxolone for 72 h prior to measurements. Generally, growth on galactose medium and ATP production were unaltered. Mitochondrial membrane potential was slightly but significantly decreased, while reactive oxygen species (ROS) production was variably decreased. Mitochondrial mass and mitochondrial DNA (mtDNA) contents were significantly increased in the patient’s cells. These results were partially confirmed by the results of oxygen consumption studies which disclosed increased maximal oxygen consumption rates in most cells and increased energy status in all treated cells. Further investigation is required to explore the precise effect of omaveloxolone on mitochondrial function in disease.
Improve the Colorectal Cancer Diagnosis Using Gut Microbiome Data
Authors: Zhou Yi-Hui , Sun George 
Published: August 2022

In the United States, colorectal cancer is the second largest cause of cancer death, and accurate early detection and identification of high-risk patients is a high priority. Although fecal screening tests are available, the close relationship between colorectal cancer and the gut microbiome has generated considerable interest. We describe a machine learning method for gut microbiome data to assist in diagnosing colorectal cancer. Our methodology integrates feature engineering, mediation analysis, statistical modeling, and network analysis into a novel unified pipeline. Simulation results illustrate the value of the method in comparison to existing methods. For predicting colorectal cancer in two real datasets, this pipeline showed an 8.7% higher prediction accuracy and 13% higher area under the receiver operator characteristic curve than other published work. Additionally, the approach highlights important colorectal cancer-related taxa for prioritization, such as high levels of Bacteroides fragilis, which can help elucidate disease pathology. Our algorithms and approach can be widely applied for Colorectal cancer prediction using either 16 S rRNA or shotgun metagenomics data.
Children with strabismus and amblyopia presented abnormal spontaneous brain activities measured through fractional amplitude of low-frequency fluctuation (fALFF)
Authors: Hu Xiao-Qin , Shi Yi-Dan , Chen Jun , You Zhipeng , Pan Yi-Cong , Ling Qian , Wei Hong , Zou Jie , Ying Ping , Liao Xu-Lin , Su Ting , Wang Yi-Xin , Shao Yi 
Published: August 2022

PurposeBased on fMRI technology, we explored whether children with strabismus and amblyopia (SA) showed significant change in fractional amplitude of low-frequency fluctuation (fALFF) values in specific brain regions compared with healthy controls and whether this change could point to the clinical manifestations and pathogenesis of children with strabismus to a certain extent.MethodsWe enrolled 23 children with SA and the same number matched healthy controls in the ophthalmology department of the First Affiliated Hospital of Nanchang University, and the whole brain was scanned by rs-fMRI. The fALFF value of each brain area was derived to examine whether there is a statistical difference between the two groups. Meanwhile, the ROC curve was made in a view to evaluate whether this difference proves useful as a diagnostic index. Finally, we analyzed whether changes in the fALFF value of some specific brain regions are related to clinical manifestations.ResultsCompared with HCs, children with SA presented decreased fALFF values in the left temporal pole: the superior temporal gyrus, right middle temporal gyrus, right superior frontal gyrus, and right supplementary motor area. Meanwhile, they also showed higher fALFF values in specific brain areas, which included the left precentral gyrus, left inferior parietal, and left precuneus.ConclusionChildren with SA showed abnormal fALFF values in different brain regions. Most of these regions were allocated to the visual formation pathway, the eye movement-related pathway, or other visual-related pathways, suggesting the pathological mechanism of the patient.
Spontaneous brain activity, graph metrics, and head motion related to prospective post-traumatic stress disorder trauma-focused therapy response
Authors: van Lutterveld Remko , Varkevisser Tim , Kouwer Karlijn , van Rooij Sanne J. H. , Kennis Mitzy , Hueting Martine , van Montfort Simone , van Dellen Edwin , Geuze Elbert 
Published: August 2022

IntroductionTrauma-focused psychotherapy for post-traumatic stress disorder (PTSD) is effective in about half of all patients. Investigating biological systems related to prospective treatment response is important to gain insight in mechanisms predisposing patients for successful intervention. We studied if spontaneous brain activity, brain network characteristics and head motion during the resting state are associated with future treatment success.MethodsFunctional magnetic resonance imaging scans were acquired from 46 veterans with PTSD around the start of treatment. Psychotherapy consisted of trauma-focused cognitive behavioral therapy (tf-CBT), eye movement desensitization and reprocessing (EMDR), or a combination thereof. After intervention, 24 patients were classified as treatment responders and 22 as treatment resistant. Differences between groups in spontaneous brain activity were evaluated using amplitude of low-frequency fluctuations (ALFF), while global and regional brain network characteristics were assessed using a minimum spanning tree (MST) approach. In addition, in-scanner head motion was assessed.ResultsNo differences in spontaneous brain activity and global network characteristics were observed between the responder and non-responder group. The right inferior parietal lobule, right putamen and left superior parietal lobule had a more central position in the network in the responder group compared to the non-responder group, while the right dorsolateral prefrontal cortex (DLPFC), right inferior frontal gyrus and left inferior temporal gyrus had a less central position. In addition, responders showed less head motion.DiscussionThese results show that areas involved in executive functioning, attentional and action processes, learning, and visual-object processing, are related to prospective PTSD treatment response in veterans. In addition, these findings suggest that involuntary micromovements may be related to future treatment success.