bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparative analysis of human adult testicular cells expressing stem Leydig cell markers in the interstitium, vasculature, and peritubular layer
Authors: Eliveld Jitske , van Daalen Saskia K. M. , de Winter‐Korver Cindy M. , van der Veen Fulco , Repping Sjoerd , Teerds Katja , van Pelt Ans M. M. 
Published: May 2020

AbstractBackgroundOrigin of human adult Leydig cells (ALCs) is not well understood. This might be partly due to limited data available on the identification and location of human precursor and stem Leydig cells (SLCs) which hampers the study on the development of ALCs.ObjectivesThe aim of the present study was to investigate whether described human (PDGFRα, NGFR) and rodent (NES, PDGFRα, THY1, NR2F2) SLC markers are expressed by a common cell population within human adult testicular interstitial cells in vivo and before and after in vitro propagation.Materials and methodsImmunohistochemical analyses were used to identify localization of human adult testicular interstitial cells expressing described SLC markers. Next, interstitial cells were isolated and cultured. The percentage of cells expressing one or more SLC markers was determined before and after culture using flow cytometry.ResultsNR2F2 and PDGFRα were present in peritubular, perivascular, and Leydig cells, while THY1 was expressed in peritubular and perivascular cells. Although NES and NGFR were expressed in endothelial cells, co‐localization with PDGFRα was found for both in vitro, although for NGFR only after culture. All marker positive cells were able to undergo propagation in vitro.DiscussionThe partly overlap in localization and overlap in expression in human testicular cells indicate that PDGFRα, NR2F2, and THY1 are expressed within the same ALC developmental lineage from SLCs. Based on the in vitro results, this is also true for NES and after in vitro propagation for NGFR.ConclusionOur results that earlier described SLC markers are expressed in overlapping human interstitial cell population opens up further research strategies aiming for a better insight in the Leydig cell lineage and will be helpful for development of strategies to cure ALC dysfunction.
Effect of serum 25‐hydroxyvitamin D levels on sperm quality and assisted reproductive technology outcomes for men of infertile Chinese couples
Authors: Chen Yilu , Liu Defeng , Zeng Lin , Xu Huiyu , Jiang Hui , Yang Rui , Wang Haining , Yan Liying , Li Rong , Qiao Jie , Zhi Xu 
Published: May 2020

AbstractIntroductionVitamin D insufficiency/deficiency is highly prevalent in China, but its effect on sperm quality and outcomes of assisted reproductive technology (ART) in men from infertile couples is not clear. This study aimed to explore the association of serum 25‐hydroxyvitamin D (25OHD) levels and semen parameters, as well as ART outcomes for men from infertile couples.Materials and methodsThis study recruited 1308 men from infertile couples who attended the Reproductive Medicine Center of Peking University Third Hospital for first time from February to August 2019 (NCT03804294). Reproductive hormones levels, semen parameters, and clinical outcomes of ART were compared between vitamin D‐deficient group (serum 25OHD ≤ 10 ng/mL), insufficient group (serum 25OHD 10‐20 ng/mL), and sufficient group (serum 25OHD ≥ 20 ng/mL).ResultsWe found 27.7% of participants were vitamin D sufficient, suggesting high prevalence of vitamin D insufficiency/deficiency in China. Reproductive hormone levels were similar between the three groups. The total number of morphologically normal spermatozoa was significantly different between the three groups in all participants, impaired semen quality subgroup, and normozoospermia subgroup (P < .05) with the adjustment of confounders (age, BMI, alcohol consumption, cigarette smoking, and physical exercise). The percentage of normal sperm morphology significantly increased with elevated serum 25OHD levels in all participants and the participants with impaired semen quality (P < .05), and the total sperm count showed significant difference in participants with impaired semen quality (P = .026). For routine in vitro fertilization and intracytoplasmic sperm injection cycles, there were no differences in fertilization rate, top‐quality embryo rate, biochemical pregnancy rate, and clinical pregnancy rate between serum 25OHD < 20 ng/mL and serum 25OHD ≥ 20 ng/mL groups.ConclusionsMales of infertile couples with higher serum 25OHD levels exhibit better results in sperm morphology, and serum 25OHD levels may contribute to total sperm number in participants with impaired semen quality, but show no effects on the ART outcomes.
Blood pressure and hypertension during pregnancy in women with polycystic ovary syndrome: Odense Child Cohort
Authors: Nielsen Julie Hougård , Birukov Anna , Jensen Richard Christian , Kyhl Henriette Boye , Jørgensen Jan Stener , Andersen Marianne Skovsager , Glintborg Dorte 
Published: May 2020

AbstractIntroductionThe aim of this study was to compare blood pressure and prevalence of pregnancy‐induced hypertension in women with polycystic ovary syndrome and the reference group throughout pregnancy.Material and methodsThis retrospective study was part of the prospective study Odense Child Cohort. Pregnant women were recruited from January 2010 to December 2012. Blood pressure was measured in 200 women with polycystic ovary syndrome and in 2197 in the reference group. Main outcome measures were blood pressure and pregnancy‐induced hypertension. Pregnancy‐induced hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg occurring after gestational week 20 at two separate visits. Mann‐Whitney U test and Chi‐square test were used to test differences between women with polycystic ovary syndrome and the reference group. Associations between polycystic ovary syndrome status (PCOS; the reference group) and blood pressure were tested using random mixed‐effect linear regression analyses with subjects as random effect to comply with repeated blood pressure measurements.ResultsMedian blood pressure was comparable in women with polycystic ovary syndrome and the reference group throughout pregnancy: systolic blood pressure 116 (111‐123) vs 119 (112‐124) (P = .06), diastolic blood pressure 72 (69‐77) vs 73 (69‐78) (P = .23) and mean arterial pressure 87 (83‐93) vs 88 (84‐92) (P = .13). In first trimester where systolic blood pressure was lower in polycystic ovary syndrome, median systolic blood pressure was 116 (111‐123) vs 119 (112‐124) mmHg (P = .04). The prevalence of pregnancy‐induced hypertension was similar in polycystic ovary syndrome and the reference group: 17/200 (8.5%) vs 178/1997 (8.9%) (P = .84). Regression analyses showed no significant associations between polycystic ovary syndrome and blood pressure.ConclusionsBlood pressure and prevalence of pregnancy‐induced hypertension were comparable in pregnant women with polycystic ovary syndrome and the reference group.
Maternal intentions towards infant sleeping practices in Ireland
Authors: O’ Brien Niamh , McGarvey Cliona , Hamilton Karina , Hayes Breda 
Published: May 2020

AbstractAimMortality from Sudden Infant Death Syndrome (SIDS) has reduced by 50%‐85% globally. Despite improvements from 1990 to 2009, the Irish SIDS rate has plateaued. Reasons for this are unclear, but may be related to a reduced parental SIDS awareness. Our study aimed to assess intentions regarding infant sleeping practices in mothers in Ireland.MethodsA cross‐sectional survey of post‐partum mothers was performed in the Rotunda Hospital over a four month period. Mothers with a history of SIDS, miscarriage or neonatal admissions were excluded.ResultsOf 451 participants, unsafe sleeping positions were intended by 15.4%, reduced by Irish ethnicity [AOR = 0.52, 95% CI = 0.277‐0.959, P = .036]. Safe sleep locations were intended by 66%, increased by Irish ethnicity [AOR = 2.6, 95% CI = 1.617‐4.191, P < .001], and reduced by young maternal age [AOR = 0.15, 95% CI = 0.03‐0.713, P = .02]. Maternal smoking was more likely in mothers with lower educational level [AOR = 3.51, 95% CI = 1.169‐10.56, P = .03]. Soft bedding use was intended by 34.8%, increased in younger mothers [AOR = 2.28, 95% CI = 1.04‐4.98, P = .04]. Breastfeeding was intended by 72.2%, decreased by Irish ethnicity [AOR = 0.14, 95% CI = 0.067‐0.271, P < .001], and low maternal education [AOR = 0.22, 95% CI = 0.117‐0.406, P < .001].ConclusionEducational campaigns on safe sleep for infants in Ireland need to address modifiable SIDS risks factors, focusing on younger, non‐Irish mothers, with lower educational attainment.
Slc26a3 deletion alters pH‐microclimate, mucin biosynthesis, microbiome composition and increases the TNFα expression in murine colon
Authors: Kini Archana , Singh Anurag K. , Riederer Brigitte , Yang Ines , Tan Xinjie , di Stefano Gabriella , Tan Qinghai , Xiao Fang , Xia Weiliang , Suerbaum Sebastian , Seidler Ursula 
Published: May 2020

AbstractAimSLC26A3 (DRA) mediates the absorption of luminal Cl− in exchange for HCO3− in the distal intestine. Its expression is lost in congenital chloride diarrhoea (CLD) and strongly decreased in the presence of intestinal inflammation. To characterize the consequences of a loss of Slc26a3 beyond disturbed electrolyte transport, colonic mucus synthesis, surface accumulation and composition, pH microclimate, microbiome composition and development of inflammation was studied in slc26a3−/− mice.MethodsThe epithelial surface pH microclimate and the surface mucus accumulation in vivo was assessed by two photon microscopy in exteriorized mid colon of anaesthetized slc26a3−/− and wt littermates. Mucus synthesis, composition and inflammatory markers were studied by qPCR and immunohistochemistry and microbiome composition by 16S rRNA sequencing.ResultsColonic pH microclimate was significantly more acidic in slc26a3−/− and to a lesser extent in cftr−/− than in wt mice. Goblet cell thecae per crypt were decreased in slc26a3−/− and increased in cftr−/− colon. Mucus accumulation in vivo was reduced, but much less so than in cftr−/− colon, which is possibly related to the different colonic fluid balance. Slc26a3−/− colonic luminal microbiome displayed strong decrease in diversity. These alterations preceded and maybe causally related to increased mucosal TNFα mRNA expression levels and leucocyte infiltration in the mid‐distal colon of slc26a3−/− but not of cftr−/− mice.ConclusionsThese findings may explain the strong increase in the susceptibility of slc26a3−/− mice to DSS damage, and offer insight into the mechanisms leading to an increased incidence of intestinal inflammation in CLD patients.
Inflammatory bowel disease and pancreatic cancer: a Scandinavian register‐based cohort study 1969‐2017
Authors: Everhov Åsa H. , Erichsen Rune , Sachs Michael C. , Pedersen Lars , Halfvarson Jonas , Askling Johan , Ekbom Anders , Ludvigsson Jonas F. , Sørensen Henrik Toft , Olén Ola 
Published: May 2020

SummaryBackgroundPatients with inflammatory bowel disease (IBD) have an increased risk of cancer.AimTo assess the risk of pancreatic cancer in IBD compared to the general population.MethodsPatients with incident IBD 1969‐2017 were identified in Danish and Swedish National Patient Registers and through biopsy data, and were matched to IBD‐free reference individuals by sex, age, place of residence and year of IBD diagnosis. We linked data to Cancer and Causes of Death Registers and examined the absolute and relative risks of pancreatic cancer and pancreatic cancer death.ResultsAmong 161 926 patients followed for 2 000 951 person years, 442 (0.27%) were diagnosed with pancreatic cancer compared to 3386 (0.21%) of the 1 599 024 reference individuals. The 20‐year cumulative incidence was 0.34% (95% confidence interval 0.30‐0.38) vs 0.29% (0.28‐0.30). The incidence rate was 22.1 (20.1‐24.2)/100 000 person years in the patients (excluding the first year of follow‐up: 20.8 [18.8‐23.0]), and 16.6 (16.0‐17.2) in the reference individuals. The hazard ratio (HR) for pancreatic cancer was increased overall: 1.43 (1.30‐1.58), in subtypes (Crohn's disease: 1.44 [1.18‐1.74]; ulcerative colitis: 1.35 [1.19‐1.53]; IBD unclassified: 1.99 [1.50‐2.64]) and especially in IBD patients with primary sclerosing cholangitis: 7.55 (4.94‐11.5). Patients and reference individuals with pancreatic cancer did not differ in cancer stage (P = 0.17) or pancreatic cancer mortality (HR 1.07 [0.95‐1.21]).ConclusionsPatients with IBD had an excess risk of pancreatic cancer, in particular patients with primary sclerosing cholangitis. However, the cumulative incidence difference after 20 years was small: 0.05%, that is, one extra pancreatic cancer per 2000 IBD patients.
Duodenal bacterial load as determined by quantitative polymerase chain reaction in asymptomatic controls, functional gastrointestinal disorders and inflammatory bowel disease
Authors: Shah Ayesha , Talley Nicholas J. , Koloski Natasha , Macdonald Graeme A. , Kendall Bradley J. , Shanahan Erin R. , Walker Marjorie M. , Keely Simon , Jones Michael P. , Morrison Mark , Holtmann Gerald J. 
Published: May 2020

SummaryBackgroundSmall intestinal bacterial overgrowth may play a role in gastrointestinal and non‐gastrointestinal diseases.AimsTo use quantitative polymerase chain reaction (qPCR) to determine and compare bacterial loads of duodenal biopsies in asymptomatic controls, and patients with functional gastrointestinal disorders (FGIDs) and inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn’s disease (CD). To define effects of gastric acid inhibition on bacterial load, explore links of bacterial load and gastrointestinal symptoms in response to a standardised nutrient challenge and compare bacterial load with glucose breath test results.MethodsIn 237 patients (63 controls, 84 FGID and 90 IBD), we collected mucosal samples under aseptic conditions during endoscopy extracted and total DNA. Bacterial load metric was calculated utilising qPCR measurements of the bacterial 16S rRNA gene, normalised to human beta‐actin expression. Standard glucose breath test and nutrient challenge test were performed.ResultsThe duodenal microbial load was higher in patients with FGID (0.22 ± 0.03) than controls (0.07 ± 0.05; P = 0.007) and patients with UC (0.01 ± 0.05) or CD (0.02 ± 0.09), (P = 0.0001). While patients treated with proton pump inhibitors (PPI) had significantly higher bacterial loads than non‐users (P < 0.05), this did not explain differences between patient groups and controls. Bacterial load was significantly (r = 0.21, P < 0.016) associated with the symptom response to standardised nutrient challenge test. Methane, but not hydrogen values on glucose breath test were associated with bacterial load measured utilising qPCR.ConclusionsUtilising qPCR, a diagnosis of FGID and treatment with PPI were independently associated with increased bacterial loads. Increased bacterial loads are associated with an augmented symptom response to a standardised nutrient challenge.
Transferability of vegetation recovery models based on remote sensing across different fire regimes
Authors: Fernández‐Guisuraga José Manuel , Suárez‐Seoane Susana , Calvo Leonor 
Published: May 2020

AbstractAimTo evaluate the transferability between fire recurrence scenarios of post‐fire vegetation cover models calibrated with satellite imagery data at different spatial resolutions within two Mediterranean pine forest sites affected by large wildfires in 2012.LocationThe northwest and east of the Iberian Peninsula.MethodsIn each study site, we defined three fire recurrence scenarios for a reference period of 35 years. We used image texture derived from the surface reflectance channels of WorldView‐2 and Sentinel‐2 (at a spatial resolution of 2 m × 2 m and 20 m × 20 m, respectively) as predictors of post‐fire vegetation cover in Random Forest regression analysies. Percentage vegetation cover was sampled in two sets of field plots with a size roughly equivalent to the spatial resolution of the imagery. The plots were distributed following a stratified design according to fire recurrence scenarios. Model transferability was assessed within each study site by applying the vegetation cover model developed for a given fire recurrence scenario to predict vegetation cover in other scenarios, iteratively.ResultsFor both wildfires, the highest model transferability between fire recurrence scenarios was achieved for those holding the most similar vegetation community composition regarding the balance of species abundance according to their plant‐regenerative traits (root mean square error [RMSE] around or lower than 15%). Model transferability performance was highly improved by fine‐grained remote‐sensing data.ConclusionsFire recurrence is a major driver of community structure and composition so the framework proposed in this study would allow land managers to reduce efforts in the context of post‐fire decision‐making to assess vegetation recovery within large burned landscapes with fire regime variability.
Prospective validation of a model‐informed precision dosing tool for vancomycin in intensive care patients
Authors: ter Heine Rob , Keizer Ron J. , van Steeg Krista , Smolders Elise J. , van Luin Matthijs , Derijks Hieronymus J. , de Jager Cornelis P.C. , Frenzel Tim , Brüggemann Roger 
Published: May 2020

AimsVancomycin is an important antibiotic for critically ill patients with Gram‐positive bacterial infections. Critically ill patients typically have severely altered pathophysiology, which leads to inefficacy or toxicity. Model‐informed precision dosing may aid in optimizing the dose, but prospectively validated tools are not available for this drug in these patients. We aimed to prospectively validate a population pharmacokinetic model for purpose model‐informed precision dosing of vancomycin in critically ill patients.MethodsWe first performed a systematic evaluation of various models on retrospectively collected pharmacokinetic data in critically ill patients and then selected the best performing model. This model was implemented in the Insight Rx clinical decision support tool and prospectively validated in a multicentre study in critically ill patients. The predictive performance was obtained as mean prediction error and relative root mean squared error.ResultsWe identified 5 suitable population pharmacokinetic models. The most suitable model was carried forward to a prospective validation. We found in a prospective multicentre study that the selected model could accurately and precisely predict the vancomycin pharmacokinetics based on a previous measurement, with a mean prediction error and relative root mean squared error of respectively 8.84% (95% confidence interval 5.72–11.96%) and 19.8% (95% confidence interval 17.47–22.13%).ConclusionUsing a systematic approach, with a retrospective evaluation and prospective verification we showed the suitability of a model to predict vancomycin pharmacokinetics for purposes of model‐informed precision dosing in clinical practice. The presented methodology may serve a generic approach for evaluation of pharmacometric models for the use of model‐informed precision dosing in the clinic.
Major bleeding risk associated with oral anticoagulant in real clinical practice. A multicentre 3‐year period population‐based prospective cohort study
Authors: Bouget Jacques , Balusson Frédéric , Maignan Maxime , Pavageau Laure , Roy Pierre‐Marie , Lacut Karine , Scailteux Lucie‐Marie , Nowak Emmanuel , Oger Emmanuel 
Published: May 2020

AimsThe objective was to compare major bleeding risk of direct oral anticoagulants (DOACs; per type and dose) with vitamin K antagonists (VKAs), irrespective of indication, using real‐world data.MethodsA population‐based prospective cohort study, using the French national health data system (SNIIRAM), identified 47 469 adults living within 5 well‐defined geographical areas, who were new users of oral anticoagulants in the period 2013–2015: 20 205 VKA users, 19 579 rivaroxaban users, 4225 dabigatran users and 3460 apixaban users. From all emergency departments within these areas, clinical data for all adults referred for bleeding was collected and medically validated. The databases were linked for common key variables. The main outcome measure was major bleeding: intracranial haemorrhage, major gastrointestinal bleeding and other major bleeding events. Hazard ratios were derived from adjusted Cox proportional hazard models. We used propensity score weighting as a sensitivity analysis, with separate analyses according to indications (atrial fibrillation or venous thromboembolism).ResultsCompared to VKAs, high and low‐dose DOACs were associated with a reduced risk of intracranial haemorrhage (adjusted hazard ratio 0.55, 95% confidence interval 0.37–0.82 and 0.54, 0.26–1.12 respectively), and a reduced risk of other major bleeding events (0.41, 0.29–0.58 and 0.41, 0.22–0.79 respectively), irrespective of duration and indication. Neither DOAC dose evidenced any significant difference from VKAs in terms of risk of major gastrointestinal bleeding.ConclusionThere is a clear benefit of using DOACs with regard to intracranial haemorrhage. The study provides new insight into major gastrointestinal and other major bleeding events.
Modelling of the relationship between infliximab exposure, faecal calprotectin and endoscopic remission in patients with Crohn's disease
Authors: Dreesen Erwin , Berends Sophie , Laharie David , D'Haens Geert , Vermeire Séverine , Gils Ann , Mathôt Ron 
Published: May 2020

AimsEvidence for the benefits of pharmacokinetic (PK) and pharmacodynamic (PD) monitoring of infliximab in patients with Crohn's disease (CD) remains scarce. We aimed to develop a population (pop)PK/PD model to characterise the infliximab dose–exposure–biomarker–response (faecal calprotectin [fCal] and endoscopic remission [ER]) relationship.MethodsData were obtained from 116 patients with CD in a phase 4 dose‐escalation study. Three sequential models were developed: a 2‐compartment popPK model linking infliximab dose to exposure; an indirect response popPK/PD model describing the inhibitory effect of infliximab exposure on fCal; and a first‐order Markov popPD model linking fCal to transitions between states of ER, no ER and dropout.ResultsInfliximab clearance increased with increasing fCal, decreasing albumin, increasing CD activity index and presence of anti‐drug antibodies. Baseline fCal increased with increasing C‐reactive protein and decreasing platelet count. Lower fCal increased the probability of attaining ER and decreased the probability of losing ER. Probability of dropping out given an earlier state of absence of ER increased with time. Large interpatient PK and PD variability resulted in a flat dose–response curve. Predicted fraction of patients achieving ER was 45% [30–61] (median [interquartile range], n = 50 000) when on 5 mg/kg infliximab (~46% observed in data). Simulations with 10 mg/kg induction doses predicted an increase to 48% [32–63]. This minor benefit at the population level argues against systematic 10 mg/kg induction dosing in all patients.ConclusionModel‐informed infliximab dose optimisation towards a predefined fCal concentration (while accounting for PK and PD variability) may improve effectiveness of infliximab therapy.