bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review and evidence assessment of monogenic gene–disease relationships in human female infertility and differences in sex development
Authors: Van Der Kelen Annelore , Okutman Özlem , Javey Elodie , Serdarogullari Münevver , Janssens Charlotte , Ghosh Manjusha S , Dequeker Bart J H , Perold Florence , Kastner Claire , Kieffer Emmanuelle , Segers Ingrid , Gheldof Alexander , Hes Frederik J , Sermon Karen , Verpoest Willem , Viville Stéphane 
Published: December 2022

Abstract

BACKGROUND
As in other domains of medicine, high-throughput sequencing methods have led to the identification of an ever-increasing number of gene variants in the fields of both male and female infertility. The increasing number of recently identified genes allows an accurate diagnosis for previously idiopathic cases of female infertility and more appropriate patient care. However, robust evidence of the gene–disease relationships (GDR) allowing the proper translation to clinical application is still missing in many cases.

OBJECTIVE AND RATIONALE
An evidence-based curation of currently identified genes involved in female infertility and differences in sex development (DSD) would significantly improve both diagnostic performance and genetic research. We therefore performed a systematic review to summarize current knowledge and assess the available GDR.

SEARCH METHODS
PRISMA guidelines were applied to curate all available information from PubMed and Web of Science on genetics of human female infertility and DSD leading to infertility, from 1 January 1988 to 1 November 2021. The reviewed pathologies include non-syndromic as well as syndromic female infertility, and endocrine and reproductive system disorders. The evidence that an identified phenotype is caused by pathogenic variants in a specific gene was assessed according to a standardized scoring system. A final score (no evidence, limited, moderate, strong, or definitive) was assigned to every GDR.

OUTCOMES
A total of 45 271 publications were identified and screened for inclusion of which 1078 were selected for gene and variant extraction. We have identified 395 genes and validated 466 GDRs covering all reported monogenic causes of female infertility and DSD. Furthermore, we present a genetic diagnostic flowchart including 105 genes with at least moderate evidence for female infertility and suggest recommendations for future research. The study did not take into account associated genetic risk factor(s) or oligogenic/polygenic causes of female infertility.

WIDER IMPLICATIONS
We have comprehensively reviewed the existing research on the genetics of female infertility and DSD, which will enable the development of diagnostic panels using validated genes. Whole genome analysis is shifting from predominantly research to clinical application, increasing its diagnostic potential. These new diagnostic possibilities will not only decrease the number of idiopathic cases but will also render genetic counselling more effective for infertile patients and their families.
Gradient discretization of a 3D-2D-1D mixed-dimensional diffusive model with resolved interface, application to the drying of a fractured porous medium
Authors: Brenner K , Chave Florent , Masson R 
Published: December 2022

Abstract
We consider a 3D-2D-1D mixed-dimensional diffusive model in a fractured porous medium coupling the 1D model along the centerline skeleton of a tubular network, the 2D model on a network of planar fractures and the 3D model in the surrounding matrix domain. The transmission conditions are based on a potential continuity assumption at matrix fracture interfaces, and on Robin type conditions at the resolved interfaces between the tubular network and the matrix and fracture network domains. The discretization of this mixed-dimensional model is formulated in the gradient discretization framework (Droniou, J., Eymard, R. & Herbin, R. (2016) Gradient schemes: generic tools for the numerical analysis of diffusion equations. ESAIM Math. Model. Numer. Anal., 50, 749–781), which covers a large class of conforming and nonconforming schemes and provides stability and error estimates based on general coercivity, consistency and limit-conformity properties. As an example of discretization fitting this framework, the mixed-dimensional version of the vertex approximate gradient (VAG) scheme is developed. It is designed to allow nonconforming meshes at the interface between the 1D and 3D-2D domains, to provide a conservative formulation with local flux expressions and to be asymptotic preserving in the limit of high transfer coefficients. Numerical experiments are provided on analytical solutions for simplified geometries, which confirm the theoretical results. Using its equivalent finite volume formulation, the VAG discretization is extended to a drying mixed-dimensional model coupling the Richards equation in a fractured porous medium and the convection diffusion of the vapor molar fraction along the 1D domain. It is applied to simulate the drying process between an operating tunnel and a radioactive waste storage rock with explicit representation of the fractures in the excavated damaged zone.
The effects of a Nutritional Packet (live yeast, vitamins C and B1, and electrolytes) offered during the final phase of feedlot steers on growth performance, nutrient digestion, and feeding behavior
Authors: Nardi Kaue T , Sarturi Jhones O , Huerta-Leidenz Nelson , Henry Darren D , Woerner Dale R , Ciriaco Francine M , Sánchez-Escalante Armida , Torrescano-Urrutia Gastón R , Silva Kaliu G S , Favero Igor G 
Published: December 2022

Abstract
The effects of a Nutritional Packet offered to beef steers during the final 64 d of the feedlot-finishing phase on growth performance, carcass characteristics, nutrient digestibility, and feeding behavior were evaluated. Angus-crossbred steers (N = 120; initial body weight = 544 ± 52 kg) were assigned to 30 pens (4 steers per pen; 15 pens per treatment) in a randomized complete block design where pen was the experimental unit. A steam-flaked corn-based finishing diet was offered to ad libitum, and the treatments were as follows: 1) control and 2) 30 g per steer-daily (dry matter basis) of the Nutritional Packet. The Nutritional Packet was formulated to provide 1.7 × 1010 CFU per steer-daily of Saccharomyces cerevisiae, 162 mg per steer-daily of vitamin C; 400 mg per steer-daily of vitamin B1; 2.4 g per steer-daily of NaCl, and 2.4 g per steer-daily of KCl. Data were analyzed using the GLIMMIX procedure of SAS with the fixed effect of treatment and the random effect of block. The average daily gain (P = 0.89), dry matter intake (P = 0.57), and gain efficiency (P = 0.82) were not affected by the inclusion of the Nutritional Packet. Digestibility of dry and organic matter, and neutral and acid detergent fiber increased (P ≤ 0.02) for steers offered the Nutritional Packet, while a trend for the same response was observed for hemicellulose (P = 0.08). The 12th rib backfat thickness increased (P = 0.02) for carcasses of steers offered the Nutritional Packet, followed by a greater (P = 0.03) calculated yield grade, whereas other carcass traits were not affected (P ≥ 0.32). While the steers under the control diet decreased behavior activities on day 63, a consistent pattern of feeding behavior measurements (activity min/d and min/kg of dry and organic matter, fiber fractions, and digestible nutrients) were observed for steers consuming the Nutritional Packet during both feeding behavior assessment periods (treatment × period interactions, P ≤ 0.03). Overall time (min/d) spent on rumination, drinking, active, chewing, and resting were not affected (P ≥ 0.28) by treatments. The Nutritional Packet offered to steers during the final 64 d on feed induced an improvement in apparent digestibility of nutrients and carcass fat deposition, without affecting growth performance or other carcass quality indices. Such effects associated with the more consistent feeding behavior of steers receiving the Nutritional Packet may warrant a shorter time on feed during the final portion of the finishing phase.
To go or not to go: variable density-dependent dispersal in small mammals
Authors: Rutherford Kate L , Cottenie Karl , Denomme-Brown Simon T 
Published: December 2022

AbstractPopulation density has been widely understood to be a key influencer of dispersal behavior; however, the generality of density-dependent (DD) dispersal in vertebrates is unclear. We conducted a review of the available empirical data on small mammal DD dispersal, distinguishing between the three dispersal stages: emigration, immigration, and transience (dispersal distance). We focused on small mammals because they are a well-studied, functionally similar group of vertebrates, with a distinct ecological importance. We also examined the effect of season, body mass, study length, and study type on the strength and direction of DD dispersal. The majority of emigration and dispersal distance studies reported negative density dependence, while immigration was mostly independent of density. No correlative patterns were detected; however, interpretation of the available data was hindered by inconsistencies in experimental and analytical approach across studies. Our results suggest that the three phases of the dispersal process may be influenced differently by density and highlight the importance of distinguishing between emigration, immigration, and transience when considering the effects of density dependence. As well, our study identifies several limitations with the current available data which limit the ability to compare DD dispersal behavior across systems, and calls for future investigations that consider all three phases of dispersal in the same system.
A case of extrapulmonary tuberculosis after use of baricitinib
Authors: Shimada Tetsuro , Maeyama Akira , Hagio Tomonobu , Muraoka Kunihide , Shibata Terufumi , Yamasaki Yutaro , Oda Taiga , Hamasaki Makoto , Yamamoto Takuaki 
Published: December 2022

ABSTRACT
Extrapulmonary tuberculosis (TB) can occur in patients treated with Janus kinase (JAK) inhibitors. We present a case of rheumatoid arthritis complicated by extrapulmonary TB following baricitinib treatment. A 45-year-old Japanese woman was diagnosed with rheumatoid arthritis at another hospital, and she subsequently started treatment with methotrexate (MTX) at 6.0 mg/week and prednisolone at 3.0 mg/day at our institute. The MTX dose was increased to 10 mg/week, and clinical remission was achieved; however, the disease activity flared up 6 months after the initial visit. Isoniazid (INH) prophylaxis was started following positive T-SPOT® screening for TB, and baricitinib (Olumiant®) was introduced 3 weeks later because of an insufficient response to MTX. INH prophylaxis was continued for 6 months. Ten months after starting INH treatment, a painless mass was observed on the left side of the patient’s neck. Magnetic resonance imaging showed enlarged lymph nodes with calcification. A subsequent biopsy and pathologic examination led to a diagnosis of tuberculous lymphadenitis, and the patient was started on anti-TB therapy. Ten months later, the patient was still in remission and doing well. Extrapulmonary TB can be difficult to diagnose because of inconsistent physical and laboratory findings. When treating patients with JAK inhibitors, physicians should be cognisant of the potential for extrapulmonary TB to develop.
Mitotic count is prognostic in IDH mutant astrocytoma without homozygous deletion of CDKN2A/B. Results of consensus panel review of EORTC trial 26053 (CATNON) and EORTC trial 22033-26033
Authors: Kros Johan M , Rushing Elisabeth , Uwimana Aimé L , Hernández-Laín Aurelio , Michotte Alex , Al-Hussaini Maysa , Bielle Franck , Mawrin Christian , Marucci Gianluca , Tesileanu C Mircea S , Stupp Roger , Baumert Brigitta , van den Bent Martin , French Pim J , Gorlia Thierry 
Published: December 2022

Abstract

Background
Gliomas with IDH1/2 mutations without 1p19q codeletion have been identified as the distinct diagnostic entity of IDH mutant astrocytoma (IDHmut astrocytoma). Homozygous deletion of Cyclin-dependent kinase 4 inhibitor A/B (CDKN2A/B) has recently been incorporated in the grading of these tumors. The question of whether histologic parameters still contribute to prognostic information on top of the molecular classification, remains unanswered. Here we evaluated consensus histologic parameters for providing additional prognostic value in IDHmut astrocytomas.

Methods
An international panel of seven neuropathologists scored 13 well-defined histologic features in virtual microscopy images of 192 IDHmut astrocytomas from EORTC trial 22033-26033 (low-grade gliomas) and 263 from EORTC 26053 (CATNON) (1p19q non-codeleted anaplastic glioma). For 192 gliomas the CDKN2A/B status was known. Consensus (agreement ≥ 4/7 panelists) histologic features were tested together with homozygous deletion (HD) of CDKN2A/B for independent prognostic power.

Results
Among consensus histologic parameters, the mitotic count (cut-off of 2 mitoses per 10 high power fields standardized to a field diameter of 0.55 mm and an area of 0.24 mm2) significantly influences PFS (P = .0098) and marginally the OS (P = .07). Mitotic count also significantly affects the PFS of tumors with HD CDKN2A/B, but not the OS, possibly due to limited follow-up data.

Conclusion
The mitotic index (cut-off 2 per 10 40× HPF) is of prognostic significance in IDHmut astrocytomas without HD CDKN2A/B. Therefore, the mitotic index may direct the therapeutic approach for patients with IDHmut astrocytomas with native CDKN2A/B status.
Endoplasmic reticulum calnexins participate in the primary root growth response to phosphate deficiency
Authors: Montpetit Jonatan , Clúa Joaquín , Hsieh Yi-Fang , Vogiatzaki Evangelia , Müller Jens , Abel Steffen , Strasser Richard , Poirier Yves 
Published: December 2022

AbstractAccumulation of incompletely folded proteins in the endoplasmic reticulum (ER) leads to ER stress, activates ER protein degradation pathways, and upregulates genes involved in protein folding. This process is known as the unfolded protein response (UPR). The role of ER protein folding in plant responses to nutrient deficiencies is unclear. We analyzed Arabidopsis (Arabidopsis thaliana) mutants affected in ER protein quality control and established that both CALNEXIN (CNX) genes function in the primary root response to phosphate (Pi) deficiency. CNX1 and CNX2 are homologous ER lectins promoting protein folding of N-glycosylated proteins via the recognition of the GlcMan9GlcNAc2 glycan. Growth of cnx1-1 and cnx2-2 single mutants was similar to that of the wild type under high and low Pi conditions, but the cnx1-1 cnx2-2 double mutant showed decreased primary root growth under low Pi conditions due to reduced meristematic cell division. This phenotype was specific to Pi deficiency; the double mutant responded normally to osmotic and salt stress. Expression of CNX2 mutated in amino acids involved in binding the GlcMan9GlcNAc2 glycan failed to complement the cnx1-1 cnx2-2 mutant. The root growth phenotype was Fe-dependent and was associated with root apoplastic Fe accumulation. Two genes involved in Fe-dependent inhibition of primary root growth under Pi deficiency, the ferroxidase LOW PHOSPHATE 1 (LPR1) and P5-type ATPase PLEIOTROPIC DRUG RESISTANCE 2 (PDR2) were epistatic to CNX1/CNX2. Overexpressing PDR2 failed to complement the cnx1-1 cnx2-2 root phenotype. The cnx1-1 cnx2-2 mutant showed no evidence of UPR activation, indicating a limited effect on ER protein folding. CNX might process a set of N-glycosylated proteins specifically involved in the response to Pi deficiency.
Direct computation of nth-order correlations of the solution of a non-linear stochastic equation
Authors: Saïdi Abdelkader , Dušek Jan 
Published: December 2022

SummaryA system of nonlinear stochastic equations excited by a Gaussian random term leading to a statistically stationary solution is considered. The Carleman linearization is used to handle the nonlinearity and the statistical characterization of the solution is formulated in terms of a sequence of correlations of increasing order. Truncated in a finite but arbitrary order, the problem leads to a linear system of equations yielding directly the correlations. It is demonstrated in two examples that, if the excitation is not too strong, the solution converges as a function of the truncation order and provides an alternative to the Monte Carlo approach consisting in ensemble averaging a large number of time-dependent random solutions. For a low-dimensional system, it is shown that replacing the tensor indexing by a numbering accounting for redundancies makes it possible to keep the total problem dimension within reasonable limits even if relatively high-order correlations are accounted for. A model reduction based on the singular value decomposition of the second-order correlation matrix is tested with success for a case of a partial differential equation (Burgers’ equation), showing that the method can be potentially applied even to high-dimensional systems originating in partial differential equations.
Sleep and neurocognitive outcome in primary school children with Robin Sequence
Authors: Wiechers Cornelia , Uhlig Simone , Poets Anette , Weise Christina , Naros Andreas , Krimmel Michael , Koos Bernd , Poets Christian F , Quante Mirja 
Published: December 2022

Abstract

Study objectives
To investigate neurocognitive and behavioral outcomes at primary school age in relation to obstructive sleep apnea (OSA) in children with Robin sequence (RS) treated with the Tuebingen palatal plate in infancy and to assess the impact of OSA in these patients.

Methods
Forty-two primary school-aged children (n = 21 with RS, n = 21 age- and sex-matched controls) underwent polysomnography, intelligence testing (“Wechsler Intelligence Scale for Children—Fifth Edition” [WISC-V]), and anthropometrics. Families completed a 7-day sleep diary and questionnaires on sleep and behavior (Children’s Sleep Habits Questionnaire [CSHQ] and the Child Behavior Checklist [CBCL]).

Results
In children with RS (17 non-syndromic, four syndromic; median age 9.7 [8.5–10.8] years), the obstructive apnea-hypopnea index (OAHI) was significantly higher than in controls (1.3 [0.4–2.7]/h vs. 0.4 [0.1–0.6]/h). Two syndromic children with RS were already on nocturnal respiratory support for OSA prior to our study, and one non-syndromic child was diagnosed with severe OSA (OAHI 57/h) despite an unremarkable medical history and questionnaire. The overall intelligence quotient in children with RS was within the normal range and did not differ between children with RS and healthy peers (102 vs. 108, p = .05). However, children with RS had values in the at-risk clinical range for externalizing behavior.

Conclusions
These children with RS showed an increased risk of OSA and behavioral problems, suggesting regular screening for OSA throughout childhood. Neurocognitive scores in children with RS were within the normal range after adequate treatment of OSA during infancy.
Managing sanctions risk in the fiduciary industry—a view from Guernsey
Authors: Arstall Laila 
Published: December 2022

Abstract
In recent years, successive waves of economic, political and environmental challenges have caused profound disruption to our personal and professional lives. Businesses have been required to assess and reassess their ability to meet the evolving realities posed by these external risks and to take stock of the people, processes and systems that protect their vulnerabilities whilst building operational resilience to meet future challenges. In this article, Laila Arstall examines the foundational blocks for trust practitioners looking to manage sanctions risk under Guernsey’s Fiduciaries Law. She highlights recent experiences in Guernsey when dealing with sanctions introduced earlier this year in response to Russia’s aggression towards Ukraine to provide some practical insights into how Guernsey trustees are tackling sanctions risks from a legal perspective.
Toxic mechanism of the Mongolian medicine “Hunqile-7” based on metabonomics and the metabolism of intestinal flora
Authors: Wang Xiye , Bao Leer , Jiang Mingyang , Li Dan , Xu Liang , Bai Meirong 
Published: December 2022

AbstractThe traditional Mongolian medicine Hunqile-7 (HQL-7), which is mainly used to relieve pain in clinic, has certain toxicity. Therefore, toxicological investigation of HQL-7 is of great significance to its safety assessment. In this study, the toxic mechanism of HQL-7 was explored based on a combination of metabolomics and intestinal flora metabolism. UHPLC-MS was used to analyze the serum, liver and kidney samples of rats after intragastric administration of HQL-7. The decision tree and K Nearest Neighbor (KNN) model were established based on the bootstrap aggregation (bagging) algorithm to classify the omics data. After samples were extracted from rat feces, the high-throughput sequencing platform was used to analyze the 16s rRNA V3-V4 region of bacteria. The experimental results confirm that the bagging algorithm improved the classification accuracy. The toxic dose, toxic intensity, and toxic target organ of HQL-7 were determined in toxicity tests. Seventeen biomarkers were identified and the metabolism dysregulation of these biomarkers may be responsible for the toxicity of HQL-7 in vivo. Several kinds of bacteria was demonstrated to be closely related to the physiological indices of renal and liver function, indicating liver and kidney damage induced by HQL-7 may be related to the disturbance of these intestinal bacteria. Overall, the toxic mechanism of HQL-7 was revealed in vivo, which not only provides a scientific basis for the safe and rational clinical use of HQL-7, but also opens up a new field of research on big data for Mongolian medicine.
Heparin Conjugate Pretreatment of Kidneys From Deceased Donors Before Transplantation: Results From the First-in-human Randomized Phase I Trial
Authors: Sedigh Amir , Lundgren Torbjörn , Lindnér Per , Nordström Johan , Magnusson Peetra , Jönsson Janniz , Carlsson Fredrik , Ploeg Rutger , Lorant Tomas 
Published: December 2022

Background.
Pretreating porcine kidneys with Corline Heparin Conjugate (CHC) during hypothermic machine perfusion (HMP) has been shown to reduce preservation injury and improve early kidney function. In this first-in-human phase I study, the safety and tolerability of transplanting CHC-pretreated kidneys were evaluated.

Methods.
CHC or placebo was added to the preservation solution during HMP of donated kidneys from deceased donors for at least 3 h before transplantation into adult patients. The primary safety endpoint was the number and severity of adverse events (AEs) and serious AEs (SAEs) during the first 30 d after transplantation.

Results.
In the first 30 d, 66 AEs were reported in 8 patients who received CHC-pretreated kidneys with 39 AEs in 8 patients who received placebo-pretreated kidneys (P = 0.1 in post hoc analysis). The most common AEs were hypertension (CHC, n = 5; placebo, n = 2) and anemia (CHC, n = 5; placebo, n = 2). Most AEs were assessed as mild (58%) or moderate (39%) and not related to treatment (95%). There were 2 SAEs reported in each group. One SAE, considered possibly related to CHC treatment, was a case of severe postprocedural hemorrhage that required reoperation. No patients needed dialysis. There were no observed rejections and no patient deaths.

Conclusions.
Pretreatment of kidneys with CHC before transplantation was considered safe and tolerable. Efficacy studies are now planned to investigate if CHC can reduce early ischemia-reperfusion injury in humans.