bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genotype–Phenotype Relationships in a Large French Cohort of Subjects with Inherited Protein C Deficiency
Authors: Alhenc-Gelas Martine , Plu-Bureau Geneviève , Mauge Laetitia , Gandrille Sophie , Présot Isabelle ,   GFHT Study Group on Genetic Thrombophilia
Published: July 2020

AbstractInherited protein C (PC) deficiency caused by mutations in the PROC gene is a well-known risk factor for venous thromboembolism. Few studies have investigated the relationship between PROC genotype and plasma or clinical phenotypes. We addressed this issue in a large retrospective cohort of 1,115 heterozygous carriers of 226 PROC pathogenic or likely pathogenic mutations. Mutations were classified in three categories according to their observed or presumed association with type I, type IIa, or type IIb PC deficiency. The study population comprised 876 carriers of type I category mutations, 55 carriers of type IIa category mutations, and 184 carriers of type IIb category mutations. PC anticoagulant activity significantly influenced risk of first venous thrombosis (p trend < 10−4). No influence of mutation category on risk of whole or unprovoked thrombotic events was observed. Both PC anticoagulant activity and genotype significantly influenced risk of venous thrombosis. Effect of detrimental mutations on plasma phenotype was ambiguous in several carriers, whatever the mutation category. Altogether, our findings confirm that diagnosing PC inherited deficiency based on plasma measurement may be difficult but show that diagnosis can be improved by PROC genotyping.
Antenatal Corticosteroids and Preterm Neonatal Morbidity and Mortality among Women with and without Diabetes in Pregnancy
Authors: Battarbee Ashley N. , Sandoval Grecio , Grobman William A. , Bailit Jennifer L. , Reddy Uma M. , Wapner Ronald J. , Varner Michael W. , Caritis Steve N. , Prasad Mona , Tita Alan T.N. , Saade George R. , Sorokin Yoram , Rouse Dwight J. , Tolosa Jorge E. ,   for the Eunice Kennedy Shriver National Institute of Child Health Human Development Maternal-Fetal Medicine Units (MFMU) Network
Published: July 2020

Objective The objective of this study was to determine whether antenatal corticosteroid exposure has a differential association with preterm neonatal morbidity among women with and without diabetes.
Study Design Secondary analysis of an observational cohort of 115,502 women and their neonates born in 25 U.S. hospitals (2008–2011). Women who delivered at 230/7 to 336/7 weeks' gestation and received antenatal corticosteroids were compared with those who did not receive antenatal corticosteroids. Women with a stillbirth and women who delivered a neonate that was not resuscitated were excluded. The primary outcome was neonatal respiratory distress syndrome or death within 48 hours. Secondary outcomes included composite neonatal morbidity (respiratory distress syndrome, necrotizing enterocolitis, grades 3–4 intraventricular hemorrhage, sepsis, or death) and mechanical ventilation. Multivariable modified Poisson regression was used to estimate the association between antenatal corticosteroid exposure and neonatal outcomes. Maternal diabetes (pregestational and gestational) was evaluated as a potential effect modifier, and sensitivity analyses were conducted to evaluate whether receipt of a partial, single, or multiple course(s) of antenatal corticosteroids influenced results.
Results A total of 4,429 women with 5,259 neonates met inclusion criteria: 3,716 (83.9%) women received antenatal corticosteroids and 713 (16.1%) did not. Of the 510 diabetic women (181 pregestational and 329 gestational), 439 (86.1%) received antenatal corticosteroids. Of the 3,919 nondiabetic women, 3,277 (83.6%) received antenatal corticosteroids. Antenatal corticosteroid exposure was not associated with respiratory distress syndrome or early death (adjusted relative risk [aRR] = 0.94, 95% confidence interval [CI]: 0.85–1.04), composite neonatal morbidity (aRR = 0.98, 95% CI: 0.89–1.07), or mechanical ventilation (aRR = 0.95, 95% CI: 0.86–1.05). There was no significant effect modification of maternal diabetes on the relationship between antenatal corticosteroids and neonatal outcomes (p > 0.05), and outcomes were similar in sensitivity analyses of partial, single, or multiple courses of corticosteroids.
Discussion Antenatal corticosteroid administered to reduce preterm neonatal morbidity does not appear to have a differential association among women with diabetes compared with those without.
Key Points
Possessive and non-identity relations in Turkic switch-reference
Authors: Bárány András , Nikolaeva Irina 
Published: July 2020

AbstractThis paper provides an overview of non-canonical patterns of switch-reference involving the converb in-(V)pin selected Turkic languages. This converb is usually described as a same-subject converb, but we show that it can conform toMcKenzie’s (2012)extended definition of “same-subject” as expressing the identity of topic situations, rather than subject referents. In addition to tracking cross-clausal subject identity,-(V)pcan be used when the possessor of the subject of one clause corefers with the subject of another clause and when the events expressed by the two clauses are in a close temporal and/or causal relationship. Based onStirling (1993)andBárány & Nikolaeva (2019), we argue that the role of possessors in Turkic switch-reference is captured by lexically specified conditions licensing the use of-(V)pwhen two subjects are in a possessive relation. Finally, we suggest that both types of non-canonical switch-reference can be seen as ensuring discourse continuity.
Health and economic benefit of China’s greenhouse gas mitigation by 2050
Authors: Xie Yang , Wu Yazhen , Xie Mingjun , Li Baodi , Zhang Hui , Ma Teng , Zhang Yuqiang 
Published: July 2020

Abstract
As the biggest greenhouse gases (GHGs) emitter, China’s climate mitigation has tremendous contributions to the global carbon and air pollutants reductions. This study is trying to extract the co-benefit on air quality, public health and economic costs in China and worldwide from China’s GHGs mitigation policy. We construct two scenarios, with moderate climate mitigation action worldwide, versus more stringent climate mitigation action in China. We use the GAINS model to predict the GHGs and air pollutants emissions in the two scenarios, and a state-of-the-art global chemical transport model to simulate the annual PM2.5 concentrations. We then use IMED|HEL, which is a health assessment model, to estimate the health impacts and economic cost of PM2.5 pollution in each country. Results show China’s mitigation has significant impact on both air quality and health improvement in eastern China and eastern Asia, a little bit impact in the rest of Asia. The improved air quality could avoid 0.37 million premature deaths due to ambient PM2.5 exposure by 2050s globally, with the majority happening in China. We use the willingness to pay method to estimate the economic benefits from the improved air quailty, and find that the reduced ambient PM2.5 concentration could avoid $406 billion and $1206 billion economic costs by 2030s and 2050s globally, with China the largest fraction of 98.5% ($400 billion) and 99.5% ($1200 billion), respectively. The reduced ambient PM2.5 exposure can also avoid 11.3 million cases morbidity globally by 2050s, due to asthma attacks and hospital admissions. Our study shows most of the economic benefits from air quality improvement due to China’s mitigation happens in China, followed by the eastern Asia (such as South Korea and Japan) and the rest of Asia. Health improvement is the main fraction of the potential benefits, such as saving health expenditure, increasing the work time.
Atomic Hartree–Fock limit calculations using Lambda functions
Authors: Hatano Yasuyo , Yamamoto Shigeyoshi 
Published: July 2020

Abstract
Nonrelativistic Hartree–Fock limit calculations are performed for the group 18 atoms using Lambda functions, which are Laguerre-type basis functions (LTFs). Since Lambda functions form a complete orthonormal set for bound states, the total energy approaches the Hartree–Fock limit monotonically upon increasing the number of expansion terms, as determined by the maximum number (N) of the principal quantum number (n) in a set. The convergence behavior of the total energy in relation to the number of expansion terms is investigated. For Rn, N = 116 is required to satisfy the convergence criterion

∣
Δ
E

/

E
∣
<

10

−
15

. Here E is the total energy and ΔE is (E(N−1) − E(N)). Total energies are obtained with 30 significant digits for He, with 14 digits for Ne, Ar, Kr, Xe, and Rn, and with 13 digits for Og. This approach gives −2.86167999561223887877554374002 au as the Hartree–Fock energy of He.
Self-referencing embedded strings (SELFIES): A 100% robust molecular string representation
Authors: Krenn Mario , Häse Florian , Nigam AkshatKumar , Friederich Pascal , Aspuru-Guzik Alan 
Published: July 2020

Abstract
The discovery of novel materials and functional molecules can help to solve some of society’s most urgent challenges, ranging from efficient energy harvesting and storage to uncovering novel pharmaceutical drug candidates. Traditionally matter engineering–generally denoted as inverse design–was based massively on human intuition and high-throughput virtual screening. The last few years have seen the emergence of significant interest in computer-inspired designs based on evolutionary or deep learning methods. The major challenge here is that the standard strings molecular representation SMILES shows substantial weaknesses in that task because large fractions of strings do not correspond to valid molecules. Here, we solve this problem at a fundamental level and introduce SELFIES (SELF-referencIng Embedded Strings), a string-based representation of molecules which is 100% robust. Every SELFIES string corresponds to a valid molecule, and SELFIES can represent every molecule. SELFIES can be directly applied in arbitrary machine learning models without the adaptation of the models; each of the generated molecule candidates is valid. In our experiments, the model’s internal memory stores two orders of magnitude more diverse molecules than a similar test with SMILES. Furthermore, as all molecules are valid, it allows for explanation and interpretation of the internal working of the generative models.
Roles of aryl hydrocarbon receptor in endothelial angiogenic responses†
Authors: Li Yan , Zhou Chi , Lei Wei , Wang Kai , Zheng Jing 
Published: July 2020

AbstractAryl hydrocarbon receptor (AhR) is a transcription factor, which can be activated by a plethora of structure-diverse ligands. Historically, AhR is known for its involvements in regulation of metabolism of xenobiotics. However, normal physiological roles of AhR have been defined in other essential biological processes, including vascular growth and function, reproduction, and immunoresponses. In contrast, aberrant expression and activation of the AhR signaling pathway occur in a variety of human diseases, many of which (e.g., preeclampsia, atherosclerosis, and hypertension) could be associated with endothelial dysfunction. Indeed, emerging evidence has shown that either exogenous or endogenous AhR ligands can induce endothelial dysfunction in either an AhR-dependent or AhR-independent manner, possibly reliant on the blood vessel origin (artery and vein) of endothelial cells. Given that the AhR signaling pathway has broad impacts on endothelial and cardiovascular function, AhR ligands, AhR, and their downstream genes could be considered novel therapeutic targets for those endothelial-related diseases. This review will discuss the current knowledge of AhR’s mediation on endothelial function and potential mechanisms underlying these actions with a focus on placental endothelial cells.
The rapamycin analog Everolimus reversibly impairs male germ cell differentiation and fertility in the mouse†
Authors: Kirsanov Oleksandr , Renegar Randall H , Busada Jonathan T , Serra Nicholas D , Harrington Ellen V , Johnson Taylor A , Geyer Christopher B 
Published: July 2020

Abstract
Sirolimus, also known as rapamycin, and its closely related rapamycin analog (rapalog) Everolimus inhibit “mammalian target of rapamycin complex 1” (mTORC1), whose activity is required for spermatogenesis. Everolimus is Food and Drug Administration approved for treating human patients to slow growth of aggressive cancers and preventing organ transplant rejection. Here, we test the hypothesis that rapalog inhibition of mTORC1 activity has a negative, but reversible, impact upon spermatogenesis. Juvenile (P20) or adult (P&gt;60) mice received daily injections of sirolimus or Everolimus for 30 days, and tissues were examined at completion of treatment or following a recovery period. Rapalog treatments reduced body and testis weights, testis weight/body weight ratios, cauda epididymal sperm counts, and seminal vesicle weights in animals of both ages. Following rapalog treatment, numbers of differentiating spermatogonia were reduced, with concomitant increases in the ratio of undifferentiated spermatogonia to total number of remaining germ cells. To determine if even low doses of Everolimus can inhibit spermatogenesis, an additional group of adult mice received a dose of Everolimus ∼6-fold lower than a human clinical dose used to treat cancer. In these animals, only testis weights, testis weight/body weight ratios, and tubule diameters were reduced. Return to control values following a recovery period was variable for each of the measured parameters and was duration and dose dependent. Together, these data indicate rapalogs exerted a dose-dependent restriction on overall growth of juvenile and adult mice and negative impact upon spermatogenesis that were largely reversed; following treatment cessation, males from all treatment groups were able to sire offspring.
Pig conceptuses secrete interferon gamma to recruit T cells to the endometrium during the peri-implantation period
Authors: McLendon Bryan A , Seo Heewon , Kramer Avery C , Burghardt Robert C , Bazer Fuller W , Johnson Greg A 
Published: July 2020

AbstractThe emerging paradigm in the immunology of pregnancy is that implantation of conceptuses does not progress in an immunologically suppressed environment. Rather, the endometrium undergoes a controlled inflammatory response during implantation as trophectoderm of elongating and implanting pig conceptuses secrete the pro-inflammatory cytokine interferon gamma (IFNG). Results of this study with pigs revealed: (1) accumulation of immune cells and apoptosis of stromal cells within the endometrium at sites of implantation during the period of IFNG secretion by conceptuses; (2) accumulation of proliferating cell nuclear antigen (PCNA)-positive T cells within the endometrium at sites of implantation; (3) significant increases in expression of T cell co-signaling receptors including programmed cell death 1 (PDCD1), CD28, cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and inducible T cell co-stimulator (ICOS), as well as chemokines CXCL9, 10, and 11 within the endometrium at sites of implantation; (4) significant increases in T cell co-signaling receptors, PDCD1 and ICOS, and chemokine CXCL9 in the endometrium of cyclic gilts infused with IFNG; and (5) identification of CD4+ (22.59%) as the major T cell subpopulation, with minor subpopulations of CD8+ (1.38%), CD4+CD25+ (1.08%), and CD4+CD8+ (0.61%) T cells within the endometrium at sites of implantation. Our results provide new insights into the immunology of implantation to suggest that trophectoderm cells of pigs secrete IFNG to recruit various subpopulations of T cells to the endometrium to contribute to a controlled inflammatory environment that supports the active breakdown and restructuring of the endometrium in response to implantation of the conceptus.
Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial
Authors: Pujol Miquel , Miró José-María , Shaw Evelyn , Aguado Jose-María , San-Juan Rafael , Puig-Asensio Mireia , Pigrau Carles , Calbo Esther , Montejo Miguel , Rodriguez-Álvarez Regino , Garcia-Pais María-Jose , Pintado Vicente , Escudero-Sánchez Rosa , Lopez-Contreras Joaquín , Morata Laura , Montero Milagros , Andrés Marta , Pasquau Juan , Arenas María-del-Mar , Padilla Belén , Murillas Javier , Jover-Sáenz Alfredo , López-Cortes Luis-Eduardo , García-Pardo Graciano , Gasch Oriol , Videla Sebastian , Hereu Pilar , Tebé Cristian , Pallarès Natalia , Sanllorente Mireia , Domínguez María-Ángeles , Càmara Jordi , Ferrer Anna , Padullés Ariadna , Cuervo Guillermo , Carratalà Jordi ,   MRSA Bacteremia (BACSARM) Trial Investigators, Soriano Alex , Almela Manel , Gómez Frederic , Chávez Fernando , Mirelis Beatriz , Padilla Emma , Dolores Pérez-Ramírez Maria , Espasa Mateu , Maria Sánchez-Díaz Ana , Cercenado Emilia , Ruiz de Gopegui Enrique , Siverio Ana , de Cueto Marina , García-Garrote Fernando , Garcia Mercè , Xercavins Mariona , Nieves Larrosa Maria 
Published: July 2020

Abstract

Background
We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis.

Methods
A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy.

Results
Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93–1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018).

Conclusions
Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events.

Clinical Trials Registration
NCT01898338.
A Comparison Between 12 Versus 20 Weeks of Trimethoprim-sulfamethoxazole as Oral Eradication Treatment for Melioidosis: An Open-label, Pragmatic, Multicenter, Non-inferiority, Randomized Controlled Trial
Authors: Anunnatsiri Siriluck , Chaowagul Wipada , Teparrukkul Prapit , Chetchotisakd Ploenchan , Tanwisaid Kittisak , Khemla Supphachoke , Narenpitak Surapong , Pattarapongsin Moragot , Kongsawasd Wirod , Pisuttimarn Pornrith , Thipmontree Wilawan , Mootsikapun Piroon , Chaisuksant Seksan , Chierakul Wirongrong , Day Nicholas P J , Limmathurotsakul Direk 
Published: July 2020

Abstract

Background
Treatment of melioidosis comprises intravenous drugs for at least 10 days, followed by oral trimethoprim-sulfamethoxazole (TMP-SMX) for 12 to 20 weeks. Oral TMP-SMX is recommended for 12 weeks in Australia and 20 weeks in Thailand.

Methods
For this open-label, pragmatic, multicenter, noninferiority, randomized controlled trial, we enrolled patients with culture-confirmed melioidosis who had received oral eradication treatment for 12 weeks and had no clinical evidence of active melioidosis. We randomly assigned patients to stop treatment (12-week regimen) or continue treatment for another 8 weeks (20-week regimen). The primary end point was culture-confirmed recurrent melioidosis within 1 year after enrollment. The noninferiority margin was a hazard ratio (HR) of 2.0. The secondary composite end point, combining overall recurrent melioidosis and mortality, was assessed post hoc.

Results
We enrolled 658 patients: 322 to the 12-week regimen and 336 to the 20-week regimen. There were 5 patients (2%) in the 12-week regimen and 2 patients (1%) in the 20-week regimen who developed culture-confirmed recurrent melioidosis (HR, 2.66; 95% confidence interval [CI], .52–13.69). The criterion for noninferiority of the primary event was not met (1-sided P = .37). However, all-cause mortality was significantly lower in the 12-week regimen group than in the 20-week regimen group (1 [.3%] vs 11 [3%], respectively; HR, 0.10; 95% CI, .01–.74). The criterion for noninferiority of the secondary composite end point, combining overall recurrent melioidosis and mortality, was met (1-sided P = .022).

Conclusions
Based on the lower total mortality and noninferiority of the secondary composite end point observed, we recommend the 12-week regimen of TMP-SMX for oral eradication treatment of melioidosis.

Clinical Trials Registration
NCT01420341.
Feasibility of evaluation of the natural history of kidney disease in the general population using electronic healthcare records
Authors: Cleary Faye , Prieto-Merino David , Hull Sally , Caplin Ben , Nitsch Dorothea 
Published: July 2020

Abstract

Background
Knowledge about the nature of long-term changes in kidney function in the general population is sparse. We aim to identify whether primary care electronic healthcare records capture sufficient information to study the natural history of kidney disease.

Methods
The National Chronic Kidney Disease Audit database covers ∼14% of the population of England and Wales. Availability of repeat serum creatinine tests was evaluated by risk factors for chronic kidney disease (CKD) and individual changes over time in estimated glomerular filtration rate (eGFR) were estimated using linear regression. Sensitivity of estimation to method of evaluation of eGFR compared laboratory-reported eGFR and recalculated eGFR (using laboratory-reported creatinine), to uncover any impact of historical creatinine calibration issues on slope estimation.

Results
Twenty-five per cent of all adults, 92% of diabetics and 96% of those with confirmed CKD had at least three creatinine tests, spanning a median of 5.7 years, 6.2 years and 6.1 years, respectively. Median changes in laboratory-reported eGFR (mL/min/1.73 m2/year) were −1.32 (CKD) and −0.60 (diabetes). Median changes in recalculated eGFR were −0.98 (CKD) and −0.11 (diabetes), underestimating decline. Magnitude of underestimation (and between-patient variation in magnitude) decreased with deteriorating eGFR. For CKD Stages 3, 4 and 5 (at latest eGFR), median slopes were −1.27, −2.49 and -3.87 for laboratory-reported eGFR and −0.89, −2.26 and −3.75 for recalculated eGFR.

Conclusions
Evaluation of long-term changes in renal function will be possible in those at greatest risk if methods are identified to overcome creatinine calibration problems. Bias will be reduced by focussing on patients with confirmed CKD.