bluuebunny/crossref_metadata_2025_split huggingface dataset:
ARGs Prevalence Among Hospitalized COVID‐19 Patients with Bacterial Infections and Resistome abundance
Authors: Aly Mahmoud 
Published: May 2022

BackgroundThe burden of antimicrobial resistance AMR worldwide is substantial and is growing. Many factors play a role in the emergence of resistance. Our microbiome is a significant reservoir for antimicrobial resistance genes (ARGs). The use and misuse of antimicrobials can select multi‐resistant bacteria and modify the repertoire of ARGs in the gut microbiota. There is clear evidence that hospitalized COVID patients have altered gut microbiota that might affect the prevalence and abundance of AMR. The World Health Organization (WHO) has reported 364 million cases worldwide. Moreover, the CDC announced 72 million positives with more than 4.2 million hospitalized cases in the US alone.ObjectiveThe purpose of the current study is to review AMGs prevalence among hospitalized COVID‐19 patients with bacterial infections and explore the alteration of resistome abundance.MethodologyWe searched the pathogen detection of the National Center for Biotechnology database for hospitalized positive COVID‐19 cases with microbiome sequencing submission using the following keywords: antimicrobial resistance, antibiotic stewardship, prevalence, epidemiology, mechanism of resistance, and COVID‐19, SARS‐CoV‐2, bacterial infection, hospitalization, healthcare‐associated infection, antibiotic resistance, antimicrobial resistance, multi‐drug resistance, Acinetobacter, Klebsiella, Streptococcus, Staphylococcus, Pseudomonas, Escherichia, Enterococcus, Methicillin‐resistant Staphylococcus aureus, New Delhi Metallo‐β‐lactamase‐producing carbapenem‐resistant enterobacterales, Severe acute respiratory syndrome coronavirus 2, Vancomycin‐resistant enterococcus. Web‐based pipelines ResistoXplorer and Qiime2 and different databases, including RESfinder, Card, and ARGminer, are used for the metagenomics analysis. They are mainly based on programming languages ‐ JavaScript (version: 1.2.0) and R (version: 4.1.0).ResultsOur preliminary results showed that, to date, 11,129 isolates were detected worldwide between the declaration of the covid as a pandemic and January 2022. Moreover, the isolates prevalence was Acinetobacter baumannii at 39.7%, followed by Klebsiella pneumonia at 32.2%, then E.coli and Shigella at 11.7%, Enterobacter at 5.4%, and Pseudomonas aeruginosa 2.5%. Finally, infections such as Klebsiella oxytoca, Citrobacter freundii, and Providencia alcalifaciens were around 10%. We explored the genetic diversity of MRGs, including: aac(6′)‐Ib′, aadA1, and(3′′)‐IIa, aph(3′′)‐Ib, aph(3′)‐Ia, aph(6)‐Id, armA, arr‐2, blaADC‐30, blaOXA‐23, blaOXA‐66, blaOXA. Currently, we are working on WGS and 16s sequencing analysis, and our future work includes data analysis on abundance profiles and exploring the resistome signatures generated from AMR metagenomics of the microbiota of positive COVID‐ hospitalized patients.ConclusionWe are anticipating that there will be a significant change take place in the gut microbiome, hence the ARGs and resistome abundance in patients with COVID‐19.
Ablation of pigment epithelium‐derived factor receptor, PEDF‐R, causes photoreceptor degeneration
Authors: Bernardo‐Colón Alexandra , Dong Lijin , Abu‐Asab Mones , Becerra Patricia 
Published: May 2022

Photoreceptor cells produce a receptor protein for pigment epithelium‐derived factor (PEDF‐R), which is encoded by the PNPLA2 gene of the patatin‐like phospholipase domain‐containing 2 family. PEDF‐R is a membrane‐linked lipase detected in the inner segments of photoreceptors. We aim to reveal the physiological role of PEDF‐R in photoreceptors by characterizing CRISPR Pnpla2 knock‐out mouse lines.CRISPR‐derived Pnpla2 knock‐out mouse lines were generated in a C57BL/6 and rd8 free background. RT‐PCR was performed from dissected retinas. Mice were evaluated for fundoscopy, electroretinography and angiography. Organs of the thorax were harvested and imaged using a LEICA microscope. Plasma was collected for lipid analyses. Eyes were enucleated and processed for histology, immunofluorescence, confocal microscopy, and transmission electron microscopy. Pnpla2‐/‐ mice had undetectable retinal Pnpla2 expression levels, enlarged whiter hearts, and lower plasma free fatty acids and triglycerides levels than their Pnpla2+/+ littermate controls. Their retinal pigment epithelial cells accumulated lipid droplets and their photoreceptors were deformed. Fundi of Pnpla2+/‐ eyes had white spots. The optic nerve area of Pnpla2‐/‐ and Pnpla2+/‐ mice had an excess of pigment. The a‐wave in Pnpla2‐/‐and Pnpla2+/‐ mice, and b‐wave in Pnpla2+/‐ mice were attenuated relative to controls. Retinal rhodopsin and opsin gene expression of Pnpla2‐/‐and Pnpla2+/‐ were lower than in controls. The immunofluorescent intensities of rhodopsin and opsin antibodies decreased in Pnpla2+/‐and Pnpla2‐/‐ photoreceptors relative to controls. The immunofluorescence of PKCα and synaptophysin antibodies (markers for bipolar cells and ribbon synapse) in the Pnpla2+/‐ retinas were lower than in controls. Ablation of Pnpla2 in mice causes malformation of photoreceptors and affects photoreceptor performance, identifying PEDF‐R as an important component for photoreceptor structure and function. These findings suggest that the absence of PEDF‐R in photoreceptor cells interrupts PEDF neurotrophic action, thereby heightening degeneration in the mice.
Dynamic Cerebral Autoregulation is Intact in Chronic Kidney Disease
Authors: Sprick Justin , Jones Toure , Jeong Jinhee , DaCosta Dana , Park Jeanie 
Published: May 2022

IntroductionChronic Kidney Disease (CKD) patients experience an elevated risk for cerebrovascular disease and neurocognitive dysfunction. One mechanism that may contribute to this heightened risk is an impairment in dynamic cerebral autoregulation; the ability of cerebral vessels to stabilize changes in cerebral blood flow during fluctuations in arterial pressure. We compared dynamic cerebral autoregulation between patients with CKD stages III‐IV, and controls (CON) without CKD matched for age, race, sex, and anti‐hypertensive medication use. We hypothesized that dynamic cerebral autoregulation would be impaired in CKD compared to CON.Methods12 CKD participants (age=63±3y, eGFR=40±3 mL/min/1.73m2), and 16 CON participants (age=58±2y), performed 2, 5‐minute bouts of repeated sit‐to‐stand maneuvers at 0.05Hz (10‐s sit, 10‐s stand) and 0.10Hz (5‐s sit, 5‐s stand) which correspond to the frequency ranges in which cerebral autoregulation is operant. The order of protocols was randomized and separated by a 5‐minute rest period. Heart rate (via ECG), arterial pressure (via finger photoplethysmography), middle cerebral artery velocity (MCAv; via transcranial Doppler ultrasonography), and end‐tidal carbon dioxide (etCO2) were measured continuously throughout both protocols. Dynamic cerebral autoregulation was characterized by performing a transfer function analysis on the mean arterial pressure‐middle cerebral artery velocity (MAP‐MCAv) relationship to derive coherence, phase, and gain. MAP‐MCAv coherence, phase, and gain were compared between groups during each of the 2 maneuvers via unpaired, 2‐tailed T‐tests.ResultsAs expected, MAP‐MCAv coherence approached 1.0 during both maneuvers (≥0.8 during 0.05Hz and ≥0.6 during 0.10Hz) with no differences between groups (P≥0.60) supporting reliability of phase and gain measures. We observed no group differences in MAP‐MCAv phase or gain during the 0.05Hz maneuver (Phase: CKD=1.4±0.09, CON=1.2±0.07, P=0.14; Gain: CKD=0.70±0.07, CON=0.75±0.05, P=0.59) suggesting no impairment in the myogenic component of cerebral autoregulation in CKD. Not all participants were able to perform the 0.10Hz maneuver due to musculoskeletal limitations, thus N=6 CKD and N=12 CON during 0.10Hz repeated sit‐to‐stand. Similarly, we observed no group differences in phase or gain measurements during the 0.10Hz maneuver (Phase: CKD=1.4±0.12, CON=1.3±0.09, P=0.35; Gain: CKD=0.69±0.08, CON=0.88±0.06, P=0.11) suggesting no impairment in the neurogenic component of cerebral autoregulation in CKD.DiscussionContrary to our hypothesis, we observed no impairment in cerebral autoregulation in CKD stages III‐IV. These findings suggest that other mechanisms likely contribute to the increased cerebrovascular disease risk observed in CKD. Future work should explore the role of other cerebrovascular regulatory mechanisms such as cerebrovascular CO2 reactivity and neurovascular coupling as potential mediators of the increased cerebrovascular disease risk exhibited in CKD.
The Epithelial‐Mesenchymal Transition and Survival in Chromophobe Renal Cell Carcinoma
Authors: Ali Waleed , Jacobs Daniel , Hoang Henry , Kajdacsy‐Balla Andre 
Published: May 2022

Introduction and ObjectiveAdvances in our understanding of the epithelial‐mesenchymal transition (EMT), how cells change polarity and surface‐expressed proteins in acquiring a more malignant state, has aided scientists in understanding cancer progression. Using in silico tools, this study examines how EMT‐related gene expression levels are associated with survival outcomes in the rare chromophobe renal cell carcinoma (ChRCC).MethodsUsing dbEMT, a curated database examining EMT literature, 1184 genes were selected as “EMT‐related” for further analysis. Kaplain‐Meier Survival plots were generated based on TCGA data on all recorded ChRCC patients for each gene (n=32 in “high” and “low” groups each based on a median cut‐off), with the step‐up Bonferroni method for multiple hypothesis testing correction being used (significance being established at p<0.004). Genes identified to be statistically significant in terms of survival outcome were selected for enrichment analysis through Cytospace to examine which biological pathways might predict survival outcome. Network analysis based on physical and predicted interactions using GeneMANIA and R was done to generate a list of non‐EMT related genes which might act with those statistically significant EMT‐related genes to affect survival, with cut‐off for for significance of both network and enrichment analysis being p<0.01. DisGeNET was used to observe if the gene expression profile of ChRCC resembled any other kind of cancer.ResultsFrom the original 1184 genes, 13 showed significant change following multiple hypothesis testing correction (p<0.0038), with all showing an increased expression relating to worse outcomes. Nine distinct processes, ranging from histone modification to SMAD2/3 nuclear pathways among others, were significantly overrepresented (p<0.01) in those 13 genes. The significant EMT‐related gene signature in ChRCC mimicked the profile of mantle cell lymphoma and urothelial carcinoma. Network analysis highlighted more than 20 additional genes which EMT‐related genes could interact with to affect survival.ConclusionsThis study showcases a small subset of EMT‐related genes significantly overexpressed in ChRCC cases with worse prognosis. Analysis highlighted pathway dysfunction regarding microtubule cytoskeletal organization and histone modification (among others) as a possible cause of increased mortality in cases of chromophobe renal cell carcinoma. Such a preliminary in silico analysis would allow for strategically targeted wet‐lab studies.
Differential regulation of L84F SOD1 in motor neurons and skeletal muscles: an insight into ALS pathology
Authors: Verma Sagar , Vats Abhishek , Devi Mandaville Gourie , Khurana Shiffali , Ganguly Nirmal K. , Chakraborti Pradip , Taneja Vibha 
Published: May 2022

Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disorder characterized by progressive deterioration of motor neurons leading to skeletal muscle denervation. Recent evidences have highlighted early involvement of neuromuscular junction (NMJ) in ALS pathogenesis. NMJ is a specialized tripartite chemical synapse which involves a well‐coordinated communication among the presynaptic motor neuron, postsynaptic skeletal muscle and terminal Schwann cells. Despite several evidences, series of events triggering NMJ disassembly in ALS are still obscure.The aim of our study is to investigate the cellular and molecular mechanisms of NMJ dysfunction in an in vitro Superoxide Dismutase 1 (SOD1) induced model of familial ALS. We have generated an ALS cell model based on a novel SOD1 mutation (L84F) identified previously in a family with a history of ALS. This mutation caused decrease in neurite outgrowth which led us to hypothesize that it may be involved in neuromuscular junction disassembly in ALS pathology.We have characterized cellular components of NMJ by differentiating hybrid spinal cord cell line (NSC‐34) into motor neurons and myoblast cell line (C2C12) into myotubes. Expression of mutant SOD1 led to decrease in mitochondrial footprints in axons and synaptic terminals and altered mitochondrial dynamics in motor neurons. However mitochondrial fission/fusion is not altered in muscles suggesting differential consequences of mutant protein. L84F SOD1 mutant readily formed detergent‐resistant aggregates in motor neurons but failed to accumulate in skeletal muscles. Skeletal muscles displayed increased levels of LC3‐II compared to motor neurons suggesting a robust proteasome machinery of muscles is responsible for clearance of mutant protein. Furthermore, motor neurons exhibited increased cell death compared to skeletal muscles when subjected to exogenous stress. Interestingly, we observed that condition media from skeletal muscles was able to rescue motor neurons from exogenous stress. We are currently identifying paracrine neuroprotective factors secreted by the muscles. It is noteworthy that mutant SOD1 led to altered expression of post synaptic acetylcholine receptor complex which might hamper neuromuscular transmission in ALS.To conclude, molecular cues from both neurons and muscles appear to play a role in compromising NMJ integrity in ALS.
Positive Association between NIRS‐derived measures of Microvascular Reactivity and Mitochondrial Capacity in the Quadriceps and Hamstrings
Authors: Gosalia Jigar G. , Delgado Jocelyn G. , Studinski Matthew G. , McCully Kevin , Vairo Giampietro G. , Proctor David N. 
Published: May 2022

BACKGROUNDDelivery of oxygen to the mitochondria is essential for oxidative phosphorylation and the production of ATP during rest and during muscle contraction. Despite widespread application of near infrared spectroscopy (NIRS), to our knowledge it has not been used to evaluate whether oxygen delivery to the mitochondria, as assessed by post‐ischemic reoxygenation parameters, is related to the oxidative capacity of the muscle.PURPOSETo determine the relation between microvascular reactivity and mitochondrial oxidative capacity in the knee joint musculature using NIRS.METHODSBilateral measurements of the vastus lateralis (VL) and medial hamstring (MH) muscles were taken in 14 moderate to highly active healthy adults (7M/7F, age: 22 ± 3 yrs, BMI: 21.3 ± 3.5 kg/m2, physical activity levels: 4190 ± 1324 MET minutes/week). Two NIRS probes (Portamon, Artinis) were secured over the respective muscle bellies, which collected data during a 30 second bout of surface electrical stimulation that caused an increase in metabolism followed by brief arterial occlusions to determine the metabolic rate of the muscle over time. A final resting metabolism measurement was taken 5 minutes after the arterial occlusions to obtain the time to half recovery of metabolic rate (NIRS k), which is a valid estimate of mitochondrial oxidative capacity. Microvascular reactivity was measured as 1) the 10‐second reoxygenation slope of the oxygen saturation signal (StO2) and 2) the half time to peak oxygenation following 5 minutes of arterial occlusion in each muscle.RESULTSThere was a significant positive association between NIRS kand the reoxygenation slope in both the VL (r = 0.64, p = 0.025) and the MH (r = 0.53, p = 0.049) muscles. NIRS kvalues were also positively associated with the time to half peak oxygenation in the VL (r = 0.65, p = 0.021) and the MH (r = 0.60, p = 0.026) muscles. There were no differences between the VL and MH muscles for NIRS kvalues (Mean ± SD: 1.78 ± 0.24 vs. 1.78 ± 0.33, p = 0.99), 10‐second reoxygenation slope (2.16 ± 0.84 vs. 1.99 ± 0.96, p = 0.65), and half time to peak oxygenation (8.4s ± 1.6 vs. 9.1s ± 2.2, p = 0.38).CONCLUSIONOur results suggest that microvascular reactivity is positively associated with the mitochondrial capacity of the knee joint musculature in this sample of healthy adults. Whether these associations exist in different clinical populations warrants future investigation.
Exercise Preconditioning Preserves Cardiac Function and Enhances Cardiac Recovery Following Dobutamine Stimulation in Doxorubicin‐Treated Rat Hearts
Authors: Haverbeck Simon Lea , Garritson Jacob , Pullen Nicholas A. , Hayward Reid 
Published: May 2022

Doxorubicin (DOX) is a chemotherapeutic drug used to treat a wide range of cancers, and its use is limited by cardiotoxicity. Exercise preconditioning has been shown to protect against DOX‐induced cardiac dysfunction when hearts are maintained under resting conditions. However, it is unclear whether this exercise‐induced protective effect is maintained when the heart is challenged during an acute exercise bout. It was hypothesized that preconditioning protects the heart against DOX cardiotoxicity when it is challenged with the β1‐adrenergic receptor agonist dobutamine (DOB), which mimics acute exercise stress.Fischer 344 rats were randomly assigned to sedentary (SED) or voluntary wheel running (WR) groups for 10 weeks. At week 11, rats were treated with either 15 mg/kg DOX or saline (SAL). Five days later, ex vivo cardiac function was assessed using an isolating working heart model at baseline, during the infusion of 7.5 μg/kg/min DOB, and during recovery.DOB infusion significantly increased left ventricular developed pressure (LVDP), maximal (dP/dtmax) and minimal (dP/dtmin) rate of left ventricular pressure development, and heart rate in all groups (p<0.05). During the recovery phase (i.e., after DOB washout) LVDP was significantly lower than baseline in all groups except for SED+DOX (baseline vs. recovery: SED+SAL: 97±2 vs. 84±5 mmHg; WR+SAL: 116±7 vs. 90±7 mmHg; SED+DOX: 83±5 vs. 76±4 mmHg; WR+DOX: 109+2 vs. 100±4 mmHg, p<0.05). SED+DOX also showed a lower baseline and recovery LVDP than WR+DOX (83±5 vs. 109±2 mmHg baseline, 76±4 vs. 100±4 mmHg recovery, p<0.05). WR+DOX showed higher dP/dtmax and lower dP/dtmin when compared to SED+DOX during DOB infusion (7311±605 vs. 5167±508 mmHg/s and ‐4059±454 vs. ‐3158±416 mmHg/s, respectively). SED+DOX dP/dtmax was significantly lower during DOB infusion and during recovery when compared to all other groups (p<0.05). During DOB and recovery, +DOX groups showed lower HR values than +SAL groups (p<0.05).These data demonstrate that exercise preconditioning preserved cardiac function after DOX exposure even when the heart is challenged, and it appeared to preserve the heart’s ability to recovery from this functional challenge. Cardioprotection seems to extend beyond rest into conditions which challenge cardiac function. These observations support the premise that exercise training can protect against cardiac dysfunction that may occur during acute exercise in cancer patients undergoing DOX treatment.
Investigation of Effects of Hyperglycaemia on the Lung Microbiome in Diabetic Mice
Authors: Vasiljevs Stanislavs , Baines Deborah 
Published: May 2022

The lungs are constantly exposed to a diversity of microbes. On average, the human inhales between 0.7 and 7000 bacterial colony forming units (CFU) every minute. The airway epithelium and the airway surface liquid (ASL) which lines the luminal surface, play a vital role in the defence against these inhaled organisms. Glucose concentration in the ASL is much lower than that of blood (approximately 12.5 times lower). It was proposed that low glucose concentration in the ASL contributes to innate protection against the growth of pathogenic organisms which can utilise glucose for growth. Previous research demonstrated that a sustained increase in blood glucose concentration (such as diabetes) led to increased glucose concentration found in the ASL in both human and animals. We therefore hypothesised that the microbial population of the lung would change in the diabetic lung.Seven‐week‐old female db/db (BKS.Cg‐+Leprdb/+Leprdb/OlaHsd) and non‐diabetic littermates (BKS.Cg‐(Lean)/OlaHsd) db/db mice and non‐diabetic littermate controls were purchased from Envigo (UK). Mice were maintained in standard animal housing in a 12h light/dark cycle; water and standard rodent chow available ad libitumand allowed to acclimatise for three weeks before lung microbiome collection. Mice were terminated with an overdose of pentobarbital (0.2ml of 100mg/ml i.p.). Blood was collected for glucose measurement. Bronchoalveolar lavage was performed and 1 mL of solution was used to extract bacterial DNA using QIAamp DNA Microbiome Kit (Qiagen). The V3‐V4‐region of the 16S rRNA gene was amplified and sequenced using 300 bp paired‐end reads on the Illumina MiSeq platform. Bioinformatic analysis was performed using Mothur v1.39.5 as per the MiSeq SOP pipeline. After removing of contaminant sequence reads, downstream statistical analyses were performed using R statistical software.The bacterial diversity in BAL samples was highly variable within and between diabetic and non‐diabetic mice. Hyperglycaemia did not affect the a‐diversity of the lung microbiome (Inverse Simpson rating). However, hyperglycaemia had a significant effect on the b‐diversity of lung microbiome (analysed with AMOVA, p=0.011, n=9) with the microbiome from diabetic mice clustering together. At the genus level, bacteria of genus Staphylococcus were more abundant in the normoglycaemic mice (n=9, p=0.019). The genus Pseudomonas were more abundant in diabetic mice (n=9, p=0.028) and Corynebacterium (n=9, p=0.0018), which are frequently found in the lung microbiome as commensal organisms, were decreased.Taken together, these data indicate that sustained hyperglycaemia modifies the lung microbiome, decreasing the abundance of commensal bacteria and promoting the growth of glucose‐utilising bacteria such as Pseudomonas which may include potential pathogenic species such as P. aeruginosa.
Towards an understanding of S100A8 and S100A9 post‐translational regulation
Authors: Polakowska Magdalena , Steczkiewicz Kamil , Wysłouch‐Cieszyńska Aleksandra 
Published: May 2022

S100A8 and S100A9 are small (10.8 kDa and 13.2 kDa), single‐domain, α‐helical proteins belonging to the S100 family of Ca2+‐binding proteins. They are moonlighting proteins exerting many important intra‐ and extracellular, physiological and pathophysiological roles related to signaling, regulation and defense. It has been a long‐term challenge to distinguish the properties of different S100A8 and S100A9 proteoforms related to various biological functions in the human organism. Many limitations have been encountered in the characterization of their structures. Most structural studies were performed for either truncated or mutated variants, especially with removed cysteine residues. The single cysteine’s of S100A8 and S100A9 are reactive, and in vivo undergo post‐translational modifications (PTMs) i.e., S‐glutathionylation or S‐nitrosylation, regulating the proteins activities in inflammatory processes.In this work, we aimed to provide the missing conformational analysis for full length, non‐mutated S100A8 and S100A9 proteins. using, in particular HDX‐MS method. Our poster presents study of consequences of S‐nitrosylation and S‐glutathionylation on cysteines reactivity and structural conformation of S100A8 and S100A9 proteins.