bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen upregulates the firing activity of hypothalamic gonadotropin‐releasing hormone (GnRH1) neurons in the evening in female medaka
Authors: Ikegami Kana , Kajihara Sho , Umatani Chie , Nakajo Mikoto , Kanda Shinji , Oka Yoshitaka 
Published: February 2022

AbstractThe reproductive function of vertebrates is regulated by the hypothalamic–pituitary–gonadal axis. In sexually mature females, gonadotropin‐releasing hormone (GnRH) neurons in the preoptic area (POA) are assumed to be responsible for a cyclic large increase in GnRH release, the GnRH surge, triggering a luteinizing hormone (LH) surge, which leads to ovulation. Precise temporal regulation of the preovulatory GnRH/LH surge is important for successful reproduction because ovulation should occur after follicular development. The time course of the circulating level of estrogen is correlated with the ovulatory cycle throughout vertebrates. However, the neural mechanisms underlying estrogen‐induced preovulatory GnRH surge after folliculogenesis still remain unclear, especially in non‐mammals. Here, we used a versatile non‐mammalian model medaka for the analysis of the involvement of estrogen in the regulation of POA‐GnRH (GnRH1) neurons. Electrophysiological analysis using a whole brain‐pituitary in vitro preparation, which maintains the hypophysiotropic function of GnRH1 neurons intact, revealed that 17β‐estradiol (E2) administration recovers the ovariectomy‐induced lowered GnRH1 neuronal activity in the evening, indicating the importance of E2 for upregulation of GnRH1 neuronal activity. The importance of E2 was also confirmed by the fact that GnRH1 neuronal activity was low in short‐day photoperiod‐conditioned females (low E2 model). However, E2 failed to upregulate the firing activity of GnRH1 neurons in the morning, suggesting the involvement of additional time‐of‐day signal(s) for triggering GnRH/LH surges at an appropriate timing. We also provide morphological evidence for the localization of estrogen receptor subtypes in GnRH1 neurons. In conclusion, we propose a working hypothesis in which both estrogenic and time‐of‐day signals act in concert to timely upregulate the firing activity of GnRH1 neurons that trigger the GnRH surge at an appropriate timing in a female‐specific manner. This neuroendocrinological mechanism is suggested to be responsible for the generation of ovulatory cycles in female teleosts in general.
Resolution of large pelvic lymphocele after incidental intracystic hemorrhage caused by percutaneous catheter drainage: Case report
Authors: Nio Ai , Okadome Masao , Shimamoto Kumi , Sonoda Kenzo , Saito Toshiaki 
Published: February 2022

AbstractWe report the case of a large pelvic lymphocele after an ovarian cancer operation, which incidentally vanished after bleeding resulting from percutaneous catheter drainage. The patient was a 74‐year‐old woman with stage IVB ovarian cancer who underwent surgery including pelvic lymph node dissection. Three months after surgery, computed tomography revealed a large (13‐cm diameter) pelvic lymphocele with associated bilateral hydronephrosis and left femoral vein thrombosis. The lymphocele was repeatedly drained by percutaneous aspiration, and the day after the second procedure, the drainage fluid became bloody. The catheter was clamped for 3 days and then removed. The lymphocele volume gradually decreased, and it was not seen on a computed tomography scan 70 days after drainage. The lymphocele did not recur prior to her death. In this case, the intracystic hemorrhage was considered to have served as a blood patch for lymph leakage.
Gastrointestinal motility disorders in patients with multiple sclerosis: A single‐center study
Authors: Khanna Lehar , Zeydan Burcu , Kantarci Orhun H. , Camilleri Michael 
Published: February 2022

AbstractBackgroundMost prevalent gastrointestinal symptoms in multiple sclerosis (MS) relate to lower bowel dysfunction, often in association with bladder manifestations.ObjectiveTo assess clinical and objective gastrointestinal motor dysfunctions in patients with MS.MethodsThis was a single‐center, retrospective study of 166 patients evaluated between 1996 and 2020. We reviewed characterization of the MS, gastrointestinal and neurological symptoms, measurements of gastrointestinal and colonic transit, and anorectal manometry.Key ResultsAt the time of the gastrointestinal evaluations of the 166 patients with MS (138 women; 83%), 111 were in the relapsing‐remitting phase and 52 were in the progressive phase. In 3 patients, disease phase was not assigned due to insufficient data. Constipation was identified in 82% (136/166) of patients. Most [103/116 (88%)] patients with bladder symptoms also had constipation or fecal incontinence. Delayed gastric emptying at 4 h and colonic transit at 24 h was identified in 16% and 7% of the cohort, respectively; 22% had accelerated gastric emptying. On anorectal manometry, resting anal sphincter pressure >90 mm Hg and rectoanal pressure differential below −50mm Hg suggested evacuation disorder in patients with constipation.Conclusions and InferencesIn addition to slow colonic transit and anorectal dysfunction leading to constipation in MS, 22% of patients had accelerated gastric emptying.
Plant–microbe eco‐evolutionary dynamics in a changing world
Authors: Angulo Violeta , Beriot Nicolas , Garcia‐Hernandez Edisa , Li Erqin , Masteling Raul , Lau Jennifer A. 
Published: February 2022

SummaryBoth plants and their associated microbiomes can respond strongly to anthropogenic environmental changes. These responses can be both ecological (e.g. a global change affecting plant demography or microbial community composition) and evolutionary (e.g. a global change altering natural selection on plant or microbial populations). As a result, global changes can catalyse eco‐evolutionary feedbacks. Here, we take a plant‐focused perspective to discuss how microbes mediate plant ecological responses to global change and how these ecological effects can influence plant evolutionary response to global change. We argue that the strong and functionally important relationships between plants and their associated microbes are particularly likely to result in eco‐evolutionary feedbacks when perturbed by global changes and discuss how improved understanding of plant–microbe eco‐evolutionary dynamics could inform conservation or even agriculture.
Hydrogen sulphide alleviates cadmium stress in Trigonella foenum‐graecum by modulating antioxidant enzymes and polyamine content
Authors: Javad S. , Shah A. A. , Ramzan M. , Sardar R. , Javed T. , Al‐Huqail A. A. , Ali H. M. , Chaudhry O. , Yasin N. A. , Ahmed S. , Hussain R. A. , Hussain I. 
Published: February 2022

ABSTRACT

Cadmium (Cd) toxicity reduces growth and yield of crops grown in metal‐polluted sites. Research was conducted to estimate the potential of hydrogen sulphide (H2S) to mitigate toxicity caused by Cd in fenugreek seedlings (Trigonella foenum‐graecum L.).

Different concentrations of CdCl2 (Cd1—1 mM, Cd2—1.5 mM, Cd3—2mM) and H2S (HS1—100 µM, HS2—150 µM, HS3—200 µM) were assessed. Seeds of fenugreek were primed with sodium hydrosulphide (NaHS), as H2S donor. Seedlings growing in Cd‐spiked media treated with H2S were harvested after 2 weeks.

Cd stress affected growth of fenugreek seedlings. Cd toxicity decreased leaf relative water content (LRWC), intercellular CO2 concentration, net photosynthesis, stomatal conductance and transpiration. However, application of H2S significantly improved seedling morphological attributes by increasing the activity of antioxidant enzymes, i.e. APX, CAT and SOD, in Cd‐contaminated soil. H2S treatment also regulated phenolic and flavonoid content.

H2S‐induced biosynthesis of spermidine (Spd) and putrescine (Put) could account for the enhancement of growth and physiological performance of fenugreek seedlings under Cd stress. H2S treatment also reduced H2O2 production (38%) and electrolyte leakage (EL, 51%) in seedlings grown in different concentrations of Cd. It is recommended to evaluate the efficacy of H2S in alleviating Cd toxicity in other crop plants.
Long‐term use of foscarnet is associated with an increased incidence of acute kidney injury in hematopoietic stem cell transplant patients: A retrospective observational study
Authors: Inose Ryo , Takahashi Katsuyuki , Takahashi Masaya , Sugimoto Takashi , Nanno Satoru , Hino Masayuki , Nagayama Katsuya 
Published: February 2022

AbstractBackgroundFoscarnet is an important drug for the treatment of cytomegalovirus infection in patients undergoing hematopoietic stem cell transplantation (HSCT). Foscarnet is often discontinued because of the development of acute kidney injury (AKI). Thus, the identification of factors leading to the development of AKI is beneficial. This study aimed to investigate the incidence of AKI and the factors influencing AKI development in HSCT patients treated with foscarnet.MethodsThis was a retrospective observational study. Patients who underwent HSCT and received foscarnet at the Department of Hematology, Osaka City University Hospital, were identified from medical records. The patients were classified into AKI and non‐AKI groups, and the risk factors associated with AKI were evaluated. For continuous variables, receiver‐operating characteristic (ROC) curve analysis was used to calculate the optimal cutoff value.ResultsThirty‐five patients (47 cases) were assigned to the AKI (51.1%, 24/47) and non‐AKI groups (48.9%, 23/47). The AKI group had a significantly longer foscarnet administration period than the non‐AKI group (p = 0.049). The appropriate cutoff value for the foscarnet administration period using the ROC curve was 27 days. The incidence of AKI was significantly higher in cases who received foscarnet for more than 27 days (11/14, 78.6%) compared to those who received less than 27 days (13/33, 39.4%) (odds ratio: 5.64, 95% confidence interval 1.32–24.2, p = 0.024).ConclusionThe incidence of AKI was 51.1% in HSCT patients treated with foscarnet, and foscarnet administration for more than 27 days may be associated with the incidence of AKI.
Impact of COVID‐19 on blood donor deferral patterns during the COVID‐19 pandemic: A retrospective analysis
Authors: Routray Suman Sudha , Ray Gopal Krushna , Prakash Satya , Sahu Ansuman , Naik Archana , Mukherjee Somnath 
Published: February 2022

AbstractBackground and ObjectivesBlood donor deferral is an essential tool for blood safety. The ongoing COVID‐19 pandemic has adversely affected blood transfusion services all over the world. But its impact on donor deferral rate and the pattern is unclear in light of the new donor deferral policy due to the COVID‐19 pandemic.Materials and MethodsThis retrospective study was divided into pre‐COVID and COVID (15 March 2019–14 March 2021). All the deferred donors were divided into six different categories: (1) medical causes, (2) surgical causes, (3) drugs and vaccination, (4) risk of transfusion‐transmitted diseases, (5) miscellaneous causes and (6) flu‐like symptoms. In addition, COVID‐related deferrals were also incorporated. All these above categories along with the donor demography were analysed by SPSS software version 25.ResultsThe donor deferral rate was 17.03% and 12.74% during the pre‐COVID and COVID periods, respectively. During the pre‐COVID period, Category 3 deferrals and during COVID period, Category 6 deferrals were significantly higher. A reversal in pattern with increased blood pressure (40.2% vs. 24.04%) over‐riding low haemoglobin (34.77% vs. 55.5%) was noted in the Category 1 deferral during the COVID period. Category 1 deferral was more in middle‐aged adults as compared to young and old adults (p < 0.05). Among middle‐aged adults, deferral due to flu‐like symptoms was also significantly more during the COVID period (p < 0.05).ConclusionCOVID‐19 significantly affected the donor pool and changed the pattern of donor deferral. Understanding donor deferral patterns may help in identifying targeted donor populations and planning donor recruitment strategies in future pandemic crises.
The legacy of A. V. Hill's Nobel Prize winning work on muscle energetics
Authors: Barclay Chris J. , Curtin Nancy A. 
Published: February 2022

AbstractA. V. Hill was awarded the 1922 Nobel Prize, jointly with Otto Meyerhof, for Physiology or Medicine for his work on energetic aspects of muscle contraction. Hill used his considerable mathematical and experimental skills to investigate the relationships among muscle mechanics, biochemistry and heat production. The main ideas of the work for which the Nobel Prize was awarded were superseded within a decade, and the legacy of Hill and Meyerhof's Nobel work was not a set of persistent, influential ideas but rather a prolonged period of extraordinary activity that advanced the understanding of how muscles work far beyond the concepts that led to the Nobel Prize. Hill pioneered the integration of mathematics into the study of physiology and pharmacology. Particular aspects of Hill's own work that remain in common use in muscle physiology include mathematical descriptions of the relationships between muscle force output and shortening velocity and between force output and calcium concentration, and the model of muscle as a contractile element in series with an elastic element. We describe some of the characteristics of Hill's broader scientific activities and then outline how Hill's work on muscle energetics was extended after 1922, as a result of Hill's own work and that of others, to the present day.
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Choriocapillaris perfusion assessed using swept source optical coherence tomographic angiography and the severity of diabetic retinopathy
Authors: Wang Wei , Guo Xiao , Chen Yifan , Xiong Kun , Gong Xia , Yuan Meng , Liang Xiaoling , Huang Wenyong 
Published: February 2022

AimsTo investigate the relationship between choriocapillaris (CC) blood perfusion and the severity of diabetic retinopathy (DR) using swept-source optical coherence tomography angiography (SS-OCTA).MethodsType 2 diabetes mellitus in the Guangzhou was recruited. DR was graded according to the standardised seven-field colour retinal images adhering to the ETDRS scale. CC perfusion was quantified by evaluating the flow deficit (FD) density, FD number and FD size using SS-OCTA. Multivariable linear regressions were used to evaluate the correlation between CC FD metrics and DR severity.ResultsA total of 1692 patients (eyes) were included in the final analysis. Participants with DR had a significantly higher FD density than the NDR group, with the differences of 1.61% (95% CI 1.04 to 2.18; p<0.001) among mild non-proliferative DR (NPDR) patients, 2.23% (95% CI 1.76 to 2.70; p<0.001) among moderate NPDR patients and 3.31% (95% CI 2.27 to 4.36; p<0.001) among severe DR than NDR patients after adjusting for confounding factors. Similarly, the higher FD number and size were also correlated with severer degree of DR (all p<0.05). Furthermore, the addition of FD density to conventional risk factors significantly improved the performance for discriminating DR from NDR patients (AUC 0. 829, 95% CI 0. 804 to 0. 855; p<0.001).ConclusionQuantitative FD density, number and size assessed by using SS-OCTA were independently correlated with the severity of DR. The assessment of the CC perfusion metrics in the macula may be a sensitive biomarker of DR changes.
May the force be with you: understanding how patellofemoral joint reaction force compares across different activities and physical interventions—a systematic review and meta-analysis
Authors: Hart Harvi F , Patterson Brooke E , Crossley Kay M , Culvenor Adam G , Khan Michaela C M , King Matthew G , Sritharan Prasanna 
Published: February 2022

ObjectiveTo systematically review and synthesise patellofemoral joint reaction force (PFJRF) in healthy individuals and those with patellofemoral pain and osteoarthritis (OA), during everyday activities, therapeutic exercises and with physical interventions (eg, foot orthotics, footwear, taping, bracing).DesignA systematic review with meta-analysis.Data sourcesMedline, Embase, Scopus, CINAHL, SportDiscus and Cochrane Library databases were searched.Eligibility criteriaObservational and interventional studies reporting PFJRF during everyday activities, therapeutic exercises, and physical interventions.ResultsIn healthy individuals, the weighted average of mean (±SD) peak PFJRF for everyday activities were: walking 0.9±0.4 body weight (BW), stair ascent 3.2±0.7 BW, stair descent 2.8±0.5 BW and running 5.2±1.2 BW. In those with patellofemoral pain, peak PFJRF were: walking 0.8±0.2 BW, stair ascent 2.5±0.5 BW, stair descent 2.6±0.5 BW, running 4.1±0.9 BW. Only single studies reported peak PFJRF during everyday activities in individuals with patellofemoral OA/articular cartilage defects (walking 1.3±0.5 BW, stair ascent 1.6±0.4 BW, stair descent 1.0±0.5 BW). The PFJRF was reported for many different exercises and physical interventions; however, considerable variability precluded any pooled estimates.SummaryEveryday activities and exercises involving larger knee flexion (eg, squatting) expose the patellofemoral joint to higher PFJRF than those involving smaller knee flexion (eg, walking). There were no discernable differences in peak PFJRF during everyday activities between healthy individuals and those with patellofemoral pain/OA. The information on PFJRF may be used to select appropriate variations of exercises and physical interventions.
Germline biomarkers predict toxicity to anti-PD1/PDL1 checkpoint therapy
Authors: Weidhaas Joanne , Marco Nicholas , Scheffler Aaron W , Kalbasi Anusha , Wilenius Kirk , Rietdorf Emily , Gill Jaya , Heilig Mara , Desler Caroline , Chin Robert K , Kaprealian Tania , McCloskey Susan , Raldow Ann , Raja Naga P , Kesari Santosh , Carrillo Jose , Drakaki Alexandra , Scholz Mark , Telesca Donatello 
Published: February 2022

BackgroundThere is great interest in finding ways to identify patients who will develop toxicity to cancer therapies. This has become especially pressing in the era of immune therapy, where toxicity can be long-lasting and life-altering, and primarily comes in the form of immune-related adverse effects (irAEs). Treatment with the first drugs in this class, anti-programmed death 1 (anti-PD1)/programmed death-ligand 1 (PDL1) checkpoint therapies, results in grade 2 or higher irAEs in up to 25%–30% of patients, which occur most commonly within the first 6 months of treatment and can include arthralgias, rash, pruritus, pneumonitis, diarrhea and/or colitis, hepatitis, and endocrinopathies. We tested the hypothesis that germline microRNA pathway functional variants, known to predict altered systemic stress responses to cancer therapies, would predict irAEs in patients across cancer types.MethodsMicroRNA pathway variants were evaluated for an association with grade 2 or higher toxicity using four classifiers on 62 patients with melanoma, and then the panel’s performance was validated on 99 patients with other cancer types. Trained classifiers included classification trees, LASSO-regularized logistic regression, boosted trees, and random forests. Final performance measures were reported on the training set using leave-one-out cross validation and validated on held-out samples. The predicted probability of toxicity was evaluated for its association, if any, with response categories to anti-PD1/PDL1 therapy in the melanoma cohort.ResultsA biomarker panel was identified that predicts toxicity with 80% accuracy (F1=0.76, area under the curve (AUC)=0.82) in the melanoma training cohort and 77.6% accuracy (F1=0.621, AUC=0.778) in the pan-cancer validation cohort. In the melanoma cohort, the predictive probability of toxicity was not associated with response categories to anti-PD1/PDL1 therapy (p=0.70). In the same cohort, the most significant biomarker of toxicity in RAC1, predicting a greater than ninefold increased risk of toxicity (p<0.001), was also not associated with response to anti-PD1/PDL1 therapy (p=0.151).ConclusionsA germline microRNA-based biomarker signature predicts grade 2 and higher irAEs to anti-PD1/PDL1 therapy, regardless of tumor type, in a pan-cancer manner. These findings represent an important step toward personalizing checkpoint therapy, the use of which is growing rapidly.
Dominant negative mutation in oxalate transporterSLC26A6associated with enteric hyperoxaluria and nephrolithiasis
Authors: Cornière Nicolas , Thomson R Brent , Thauvin Stéphanie , Villoutreix Bruno O , Karp Sophie , Dynia Diane W , Burlein Sarah , Brinkmann Lennart , Badreddine Alaa , Dechaume Aurélie , Derhourhi Mehdi , Durand Emmanuelle , Vaillant Emmanuel , Froguel Philippe , Chambrey Régine , Aronson Peter S , Bonnefond Amélie , Eladari Dominique 
Published: February 2022

BackgroundNephrolithiasis (NL) is a complex multifactorial disease affecting up to 10%–20% of the human population and causing a significant burden on public health systems worldwide. It results from a combination of environmental and genetic factors. Hyperoxaluria is a major risk factor for NL.MethodsWe used a whole exome-based approach in a patient with calcium oxalate NL. The effects of the mutation were characterised using cell culture and in silico analyses.ResultsWe identified a rare heterozygous missense mutation (c.1519C>T/p.R507W) in theSLC26A6gene that encodes a secretory oxalate transporter. This mutation cosegregated with hyperoxaluria in the family. In vitro characterisation of mutant SLC26A6 demonstrated that Cl−-dependent oxalate transport was dramatically reduced because the mutation affects both SLC26A6 transport activity and membrane surface expression. Cotransfection studies demonstrated strong dominant-negative effects of the mutant on the wild-type protein indicating that the phenotype of patients heterozygous for this mutation may be more severe than predicted by haploinsufficiency alone.ConclusionOur study is in line with previous observations made in the mouse showing thatSLC26A6inactivation can cause inherited enteric hyperoxaluria with calcium oxalate NL. Consistent with an enteric form of hyperoxaluria, we observed a beneficial effect of increasing calcium in the patient’s diet to reduce urinary oxalate excretion.
Constructive or Optimized: An Overview of Strategies to Design Networks for Time-Critical Applications
Authors: Gavriluţ Voica , Pruski Aleksander , Berger Michael Stübert 
Published: February 2022

Distributed systems are pervasive nowadays, being found in different areas, from smart toys to smart factories. As the usage of such systems increases, so does their complexity and design. Therefore, this work aims to overview the methods for designing networks that accommodate time-constrained distributed applications.The work starts with a history of time-aware Ethernet-based protocols. Then, it continues with an overview of the design strategies from the literature. For each research paper, there are presented the model, addressed problem, exploration strategy, and results. Furthermore, for each type of problem are identified the constructive and optimization design strategies. Regarding the results, this work investigates the improvements of reliability, timeliness, and network cost.