bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum LH levels are associated to serum insulin and Anti‐Müllerian hormone levels in women with both functional hypothalamic amenorrhoea and polycystic ovarian morphology
Authors: Makolle Sarah , Catteau‐Jonard Sophie , Robin Geoffroy , Dewailly Didier 
Published: March 2023

AbstractObjectiveThe aim of the study was to investigate whether serum Luteinizing Hormone (LH) levels in women with Functional Hypothalamic Amenorrhoea (FHA) and Polycystic Ovarian Morphology (PCOM) are still associated to Body Mass Index (BMI) and/or serum insulin and/or Anti‐Müllerian Hormone (AMH) levels using a larger population of FHA.DesignRetrospective observational study (2006–2020).ParticipantsData from 62 FHA patients were used for this study using strict criteria to define them.MeasurementsSerum LH, FSH, 17‐hydroxyprogesterone (17‐OHP), dehydroepiandrosterone sulphate (DHEA‐S), androstenedione, total testosterone, prolactin, Sex Hormone Binding Globulin (SHBG) and AMH levels were measured by immunoassay. To homogenize the AMH values, we converted those obtained after 2015. We defined PCOM with strict criteria: a follicle number per ovary (FNPO) ≥12 or ≥20 per ovary, depending on the date on which the assessment was carried out and the ultrasound device.ResultsForty‐two percentage of our FHA population had PCOM. The PCOM+ group had significantly higher ranks of BMI (p = .024) and serum AMH levels (p = .0001) and significantly lower ranks of serum FSH levels (p = .002). LH was positively correlated with fasting insulin (p = .011) and with AMH (p = .035) in the PCOM+ group only but not with BMI. There was a positive correlation between LH and FSH in both groups.ConclusionOur study suggests that GnRH insufficiency in women with PCOM unravels some mechanisms of LH regulation that are poorly documented in the literature and may involve a direct pituitary effect, as suggested by our results with serum insulin and AMH levels.
Evonne: A Visual Tool for Explaining Reasoning with OWL Ontologies and Supporting Interactive Debugging
Authors: Méndez J. , Alrabbaa C. , Koopmann P. , Langner R. , Baader F. , Dachselt R. 
Published: March 2023

AbstractOWL is a powerful language to formalize terminologies in an ontology. Its main strength lies in its foundation on description logics, allowing systems to automatically deduce implicit information through logical reasoning. However, since ontologies are often complex, understanding the outcome of the reasoning process is not always straightforward. Unlike already existing tools for exploring ontologies, our visualization tool Evonne is tailored towards explaining logical consequences. In addition, it supports the debugging of unwanted consequences and allows for an interactive comparison of the impact of removing statements from the ontology. Our visual approach combines (1) specialized views for the explanation of logical consequences and the structure of the ontology, (2) employing multiple layout modes for iteratively exploring explanations, (3) detailed explanations of specific reasoning steps, (4) cross‐view highlighting and colour coding of the visualization components, (5) features for dealing with visual complexity and (6) comparison and exploration of possible fixes to the ontology. We evaluated Evonne in a qualitative study with 16 experts in logics, and their positive feedback confirms the value of our concepts for explaining reasoning and debugging ontologies.
Systems‐based digital twins to help characterize clinical dose–response and propose predictive biomarkers in a Phase I study of bispecific antibody, mosunetuzumab, in NHL
Authors: Susilo Monica E. , Li Chi‐Chung , Gadkar Kapil , Hernandez Genevive , Huw Ling‐Yuh , Jin Jin Y. , Yin Shen , Wei Michael C. , Ramanujan Saroja , Hosseini Iraj 
Published: March 2023

AbstractPhase I oncology clinical trials often comprise a limited number of patients representing different disease subtypes who are divided into cohorts receiving treatment(s) at different dosing levels and schedules. Here, we leverage a previously developed quantitative systems pharmacology model of the anti‐CD20/CD3 T‐cell engaging bispecific antibody, mosunetuzumab, to account for different dosing regimens and patient heterogeneity in the phase I study to inform clinical dose/exposure‐response relationships and to identify biological determinants of clinical response. We developed a novel workflow to generate digital twins for each patient, which together form a virtual population (VPOP) that represented variability in biological, pharmacological, and tumor‐related parameters from the phase I trial. Simulations based on the VPOP predict that an increase in mosunetuzumab exposure increases the proportion of digital twins with at least a 50% reduction in tumor size by day 42. Simulations also predict a left‐shift of the exposure‐response in patients diagnosed with indolent compared to aggressive non‐Hodgkin's lymphoma (NHL) subtype; this increased sensitivity in indolent NHL was attributed to the lower inferred values of tumor proliferation rate and baseline T‐cell infiltration in the corresponding digital twins. Notably, the inferred digital twin parameters from clinical responders and nonresponders show that the potential biological difference that can influence response include tumor parameters (tumor size, proliferation rate, and baseline T‐cell infiltration) and parameters defining the effect of mosunetuzumab on T‐cell activation and B‐cell killing. Finally, the model simulations suggest intratumor expansion of pre‐existing T‐cells, rather than an influx of systemically expanded T‐cells, underlies the antitumor activity of mosunetuzumab.
Identifying clinical features and blood biomarkers associated with mild cognitive impairment in Parkinson disease using machine learning
Authors: Deng Xiao , Ning Yilin , Saffari Seyed Ehsan , Xiao Bin , Niu Chenglin , Ng Samuel Yong Ern , Chia Nicole , Choi Xinyi , Heng Dede Liana , Tan Yi Jayne , Ng Ebonne , Xu Zheyu , Tay Kay‐Yaw , Au Wing‐Lok , Ng Adeline , Tan Eng‐King , Liu Nan , Tan Louis C. S. 
Published: March 2023

AbstractBackground and purposeA broad list of variables associated with mild cognitive impairment (MCI) in Parkinson disease (PD) have been investigated separately. However, there is as yet no study including all of them to assess variable importance. Shapley variable importance cloud (ShapleyVIC) can robustly assess variable importance while accounting for correlation between variables. Objectives of this study were (i) to prioritize the important variables associated with PD‐MCI and (ii) to explore new blood biomarkers related to PD‐MCI.MethodsShapleyVIC‐assisted variable selection was used to identify a subset of variables from 41 variables potentially associated with PD‐MCI in a cross‐sectional study. Backward selection was used to further identify the variables associated with PD‐MCI. Relative risk was used to quantify the association of final associated variables and PD‐MCI in the final multivariable log‐binomial regression model.ResultsAmong 41 variables analysed, 22 variables were identified as significantly important variables associated with PD‐MCI and eight variables were subsequently selected in the final model, indicating fewer years of education, shorter history of hypertension, higher Movement Disorder Society–Unified Parkinson's Disease Rating Scale motor score, higher levels of triglyceride (TG) and apolipoprotein A1 (ApoA1), and SNCA rs6826785 noncarrier status were associated with increased risk of PD‐MCI (p < 0.05).ConclusionsOur study highlighted the strong association between TG, ApoA1, SNCA rs6826785, and PD‐MCI by machine learning approach. Screening and management of high TG and ApoA1 levels might help prevent cognitive impairment in early PD patients. SNCA rs6826785 could be a novel therapeutic target for PD‐MCI. ShapleyVIC‐assisted variable selection is a novel and robust alternative to traditional approaches for future clinical study to prioritize the variables of interest.
Modes of ingress by larvae and juveniles of marine fishes into estuaries: From microtidal to macrotidal systems
Authors: Whitfield Alan K. , Potter Ian C. , Neira Francisco J. , Houde Edward D. 
Published: March 2023

AbstractWe review published research on the ingress of larvae and early juveniles of marine fishes into estuaries subjected to different tidal regimes and provide perspectives on the abilities and responses of these early‐life stages to the physico‐chemical, hydrodynamic and biological drivers that facilitate such ingress. We focus on documenting ingress and the mechanisms employed by early‐stage fishes from coastal waters to enter different types of microtidal and macrotidal estuaries but also include information on ingress into mesotidal systems. Spawning localities for estuary‐associated marine fishes are assessed with respect to ontogeny of larvae and their ability to ingress estuaries during the preflexion and postflexion stages. The processes and physico‐chemical cues employed by larvae and early juveniles to locate estuaries are reviewed, with olfactory cues being recognised as especially important. Particular emphasis is directed to vertical migratory behaviours and selective tidal stream transport (STST) employed by many larvae ingressing macrotidal estuaries, contrasting with mainly passive flood‐tide entry and active swimming modes typically used by larvae and early juveniles that enter microtidal estuaries and estuarine lakes and lagoon systems.
Endangered spined loach Cobitis species in Southwest Germany: A complex network of native, hybrid and newly emerged populations
Authors: Roch Samuel , Bartolin Patrick , Vonlanthen Pascal , Baer Jan , Grundmüller Simon , Epp Laura S. , Brinker Alexander 
Published: March 2023

AbstractSuccessful conservation of cryptic species such as representatives of the genus Cobitis presents a challenge for fishery managers. Only Cobitis taenia L. is currently assumed to occur in southwest Germany, where it is classified as critically endangered. Established genetic markers and eDNA analysis identified three Cobitis species in the study area. Cobitis taenia and Cobitis elongatoides were widely distributed in the Rhine River system, primarily forming hybrid species complexes in which polyploid individuals dominate but coexist with diploid parent species. A third non‐native species, Cobitis bilineata, has recently become established in the southern part of the Rhine to which it probably migrated naturally via the connected Aare River system. In the Danube River catchment, two populations, including one previously thought to be extinct, comprise both diploid and polyploid representatives of C. elongatoides. Our results provide an important basis for more targeted conservation strategies for Cobitis species currently found in the region.
Stakeholder Participation in High‐Resolution Monitoring of Salt Contamination
Authors: Metcalf Meredith J. , Higgins Mark A. , Robbins Gary A. 
Published: March 2023

AbstractGroundwater contamination of bedrock domestic wells by road salt is an ever‐increasing problem in the Northeast United States. Given the many factors that influence salt transport to wells, the timeframe of salt impacts cannot be readily determined. As such, one cannot optimize quarterly monitoring for assessing the extent of a problem, its source or the effectiveness of remedial measures. Although the use of high‐frequency monitoring by installing pressure/electrical conductance probes in wells can be conducted to help determining salt contamination changes with time, this can be costly given the application to multiple wells. In addition, there are logistical issues with regard to probe placement in a drinking water well. In this study a stakeholder participated in high‐resolution monitoring of salt contamination using a chloride field test kit. The daily stakeholder water quality monitoring was highly correlated to the specific conductance results obtained with a pressure/conductivity probe. Voluntary stakeholder participation in monitoring can offer a lower cost means of high‐frequency monitoring of salt contamination changes with time.
Efficacy and safety of the B‐domain‐deleted TQG202 for on‐demand treatment in moderate and severe haemophilia A patients: A multicentre, single‐arm trial
Authors: Sun Zimin , Xi Yaming , Liu Wei , Yang Linhua , Wang Xuefeng , Jin Chenghao , Jia Haifei , Zhang Lei 
Published: March 2023

AbstractIntroductionOn‐demand treatment is the most common treatment strategy for haemophilia A in China.AimThis study aims to evaluate the efficacy and safety of a human‐derived B‐domain‐deleted recombinant factor VIII (TQG202) in the on‐demand treatment of bleeding episodes in moderate/severe haemophilia A patients.MethodsThis multicentre, single‐arm clinical trial enrolled moderate/severe haemophilia patients previously treated with FVIII concentrates for ≥50 exposure days (EDs) from May 2017 to October 2019. TQG202 was injected intravenously on‐demand for bleeding episode management. The primary endpoints were the infusion efficiency at 15 and 60 min after the first administration and haemostatic efficacy of the first bleeding episode. Safety was also monitored.ResultsFifty‐six participants were enrolled with a median age of 24.5 (range: 12–64) years old. The median total dose of TQG202 was 29,250 IU per participant (range: 1750–2,02,500), and the median number of administrations was 24.5 (2–116). The median infusion efficiency at 15 and 60 min after the first administration was 155.4% and 145.2%, respectively. Among the 48 first bleeding episodes evaluated, 47 (83.9%, 95% CI: 71.7%–92.4%) had a haemostatic efficacy rating of excellent or good. Eleven (19.6%) participants had treatment‐related adverse events (TRAEs), but no ≥grade 3 TRAE was observed. Inhibitor development (0.6BU) was observed in one participant (1.8%) after 22 EDs, but was undetectable after 43 EDs.ConclusionTQG202 for on‐demand treatment in moderate/severe haemophilia A shows effective control of the bleeding symptoms, with a low incidence of adverse events and inhibitors development.
A decision support tool for the first stage of the tempering process of organic wheat grains in a mill
Authors: Parrenin Loïc , Danjou Christophe , Agard Bruno , Beauchemin Robert 
Published: March 2023

SummaryWheat tempering conditions grains before a milling process begins. Process adjustments must be made to reach a desired level of flour quality and yield, depending on multiple factors. This article aims to develop a decision support tool to help operators adjust the first‐stage tempering parameters. It is based on a regression model that predicts an increase in organic wheat moisture content according to the properties of the wheat (initial wheat moisture content, wheat protein content and wheat temperature), process parameters (targeted wheat moisture content, wheat flow rate, water flow rate, wheat quantity and resting time) and tempering conditions (water quantity, average day temperature and average day humidity). The increase in wheat moisture achieved during the first tempering stage varies between 0% and 5%. Five regression models were compared: OLS, LASSO, RIDGE, ElasticNet and XGBoost. The models have been developed and tested from a case study at an organic wheat mill. The results indicate that the LASSO model outperformed others, with an average prediction error of 0.428%. The model showed the importance of humidity and temperature factors during the tempering process. The flow of water and wheat were the most influential parameters for an increase in wheat moisture content.
The leukotriene B4 receptors BLT1 and BLT2 as potential therapeutic targets
Authors: Yokomizo Takehiko , Shimizu Takao 
Published: March 2023

SummaryLeukotriene B4 (LTB4) was recognized as an arachidonate‐derived chemotactic factor for inflammatory cells and an important drug target even before the molecular identification of its receptors. We cloned the high‐ and low‐affinity LTB4 receptors, BLT1 and BLT2, respectively, and examined their functions by generating and studying gene‐targeted mice. BLT1 is involved in the pathogenesis of various inflammatory and immune diseases, including asthma, psoriasis, contact dermatitis, allergic conjunctivitis, age‐related macular degeneration, and immune complex‐mediated glomerulonephritis. Meanwhile, BLT2 is a high‐affinity receptor for 12‐hydroxyheptadecatrienoic acid, which is involved in the maintenance of dermal and intestinal barrier function, and the acceleration of skin and corneal wound healing. Thus, BLT1 antagonists and BLT2 agonists are promising candidates in the treatment of inflammatory diseases.
Island volcanism predicts pheomelanin‐based plumage colouration in a cosmopolitan raptor
Authors: Romano Andrea , Séchaud Robin , Montanarella Luca , Roulin Alexandre 
Published: March 2023

AbstractAimPheomelanin is a pigment responsible for yellowish‐to‐reddish colours of vertebrate teguments. Its biosynthesis is favoured under high concentration of intracellular thiols, which, in turn, can depend on the environmental exposure to sulphur. Thus, pheomelanin production should be more intense and frequent in environments characterized by high level of sulphur, such as volcanic regions. In this study, we aimed at addressing this hypothesis by investigating variation in plumage colour of insular populations of the cosmopolitan barn owl (Tyto alba species complex) according to the presence of soils of volcanic origin (i.e. andosols) and recent volcanic activity.LocationWorld.TaxonBarn owl species complex.MethodsWe measured plumage colouration of more than 2000 museum specimens from 50 islands and archipelagos worldwide. We then compared plumage colouration between populations living on volcanic (i.e. where andosols and/or recent volcanic activity are present) and non‐volcanic islands/archipelagos.ResultsConsistently with the prediction, plumage colouration is significantly darker (i.e. pheomelanic) on islands/archipelagos where andosols and/or recent volcanic activity are present than absent, although this environmental factor explains a small fraction of plumage colour variability across islands (<10%). Similar results were obtained when specimens' sex and climatic predictors were included in the analyses.Main ConclusionsBecause excessive intracellular levels of thiols can be toxic, pheomelanin synthesis may function as a mechanism keeping these compounds below the toxicity threshold and limiting their detrimental effects on physiology. Darker plumage may also be favoured because it promotes background matching against the dark environment typical of volcanic islands (dense vegetation cover and/or dark soil). Our results add to the little evidence that the environmental exposure of compounds that are involved in melanin biosynthesis can affect animal pigmentation and suggest that soil composition may be a factor that affects melanogenesis, possibly contributing to generate spatial variation in pheomelanin‐based traits in animals.
Sexual dimorphism and reproductive biology of Cephalocassis borneensis (Siluriformes: Ariidae), a paternal mouth‐brooding fish in the Mekong River
Authors: Le Ngoc‐Son , Duong Thuy‐Yen 
Published: March 2023

AbstractInformation on the reproductive biology of fish species is essential for fisheries management, conservation and culture potential assessment. Therefore, this study aimed to understand the sex‐based morphological differences and reproductive characteristics of Cephalocassis borneensis, an ariid species with a rapid decline of wild populations. Fish samples were collected monthly from local fishermen (n = 1092) in the Vietnamese Mekong River over a year. Morphological analyses revealed that sexual dimorphism was observed in mature, but not immature, fish. The length at first maturity (Lm) was smaller for males (11.5 cm) than for females (12.5 cm). Mature males had larger head length and pre‐pectoral distance than mature females, increasing the space for oral incubation of fertilized eggs and larvae in males. Conversely, females were larger in three head parameters (head angle, head width and head depth) and three abdomen parameters (body deep, ventral fin length and distance between pectoral and ventral fin) involved in ovary development. Paternal mouth‐brooding behaviour is an important reproductive strategy in C. borneensis to increase offspring survival. Monthly variations in gonado‐somatic index and condition factor (K) and the presence of maturation stages indicated that C. borneensis spawns year‐round, mainly in the rainy season from June to October. This species' fecundity was relatively low, from 10 to 31 eggs per female of quite large sizes (about 7.30 ± 0.68 mm in diameter). Besides, non‐functional oocytes (hyaline eggs) of smaller size (<3 mm) were found in the females' ovaries. Low fecundity with large eggs and paternal care indicated that the species is an equilibrium strategist. These characteristics are critical in developing ariid species conservation plans, such as setting the time and mesh‐size for fishing, and domestication programmes in artificial conditions.
A cell wall invertase modulates resistance to fusarium crown rot and sharp eyespot in common wheat
Authors: Lv Guoguo , Zhang Yixiao , Ma Lin , Yan Xiangning , Yuan Mingjie , Chen Jianhui , Cheng Yongzhen , Yang Xi , Qiao Qi , Zhang Leilei , Niaz Mohsin , Sun Xiaonan , Zhang Qijun , Zhong Shaobin , Chen Feng 
Published: March 2023

ABSTRACTFusarium crown rot (FCR) and sharp eyespot (SE) are serious soil‐borne diseases in wheat and its relatives that have been reported to cause wheat yield losses in many areas. In this study, the expression of a cell wall invertase gene, TaCWI‐B1, was identified to be associated with FCR resistance through a combination of bulk segregant RNA sequencing and genome resequencing in a recombinant inbred line population. Two bi‐parental populations were developed to further verify TaCWI‐B1 association with FCR resistance. Overexpression lines and ethyl methanesulfonate (EMS) mutants revealed TaCWI‐B1 positively regulating FCR resistance. Determination of cell wall thickness and components showed that the TaCWI‐B1‐overexpression lines exhibited considerably increased thickness and pectin and cellulose contents. Furthermore, we found that TaCWI‐B1 directly interacted with an alpha‐galactosidase (TaGAL). EMS mutants showed that TaGAL negatively modulated FCR resistance. The expression of TaGAL is negatively correlated with TaCWI‐B1 levels, thus may reduce mannan degradation in the cell wall, consequently leading to thickening of the cell wall. Additionally, TaCWI‐B1‐overexpression lines and TaGAL mutants showed higher resistance to SE; however, TaCWI‐B1 mutants were more susceptible to SE than controls. This study provides insights into a FCR and SE resistance gene to combat soil‐borne diseases in common wheat.