bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of de novo variants in nonsyndromic cleft lip with/without cleft palate patients with low polygenic risk scores
Authors: Ishorst Nina , Henschel Leonie , Thieme Frederic , Drichel Dmitriy , Sivalingam Sugirthan , Mehrem Sarah L. , Fechtner Ariane C. , Fazaal Julia , Welzenbach Julia , Heimbach André , Maj Carlo , Borisov Oleg , Hausen Jonas , Raff Ruth , Hoischen Alexander , Dixon Michael , Rada‐Iglesias Alvaro , Bartusel Michaela , Rojas‐Martinez Augusto , Aldhorae Khalid , Braumann Bert , Kruse Teresa , Kirschneck Christian , Spanier Gerrit , Reutter Heiko , Nowak Stefanie , Gölz Lina , Knapp Michael , Buness Andreas , Krawitz Peter , Nöthen Markus M. , Nothnagel Michael , Becker Tim , Ludwig Kerstin U. , Mangold Elisabeth 
Published: December 2022

AbstractBackgroundNonsyndromic cleft lip with/without cleft palate (nsCL/P) is a congenital malformation of multifactorial etiology. Research has identified >40 genome‐wide significant risk loci, which explain less than 40% of nsCL/P heritability. Studies show that some of the hidden heritability is explained by rare penetrant variants.MethodsTo identify new candidate genes, we searched for highly penetrant de novo variants (DNVs) in 50 nsCL/P patient/parent‐trios with a low polygenic risk for the phenotype (discovery).We prioritized DNV‐carrying candidate genes from the discovery for resequencing in independent cohorts of 1010 nsCL/P patients of diverse ethnicities and 1574 population‐matched controls (replication). Segregation analyses and rare variant association in the replication cohort, in combination with additional data (genome‐wide association data, expression, protein–protein‐interactions), were used for final prioritization.ConclusionIn the discovery step, 60 DNVs were identified in 60 genes, including a variant in the established nsCL/P risk gene CDH1. Re‐sequencing of 32 prioritized genes led to the identification of 373 rare, likely pathogenic variants. Finally, MDN1 and PAXIP1 were prioritized as top candidates. Our findings demonstrate that DNV detection, including polygenic risk score analysis, is a powerful tool for identifying nsCL/P candidate genes, which can also be applied to other multifactorial congenital malformations.
Autophagy markers are dysregulated in the endometrial tissues of patients with unexplained repeated implantation failure
Authors: Zhu Yuanchang , Zhang Zhiqin , Ma Zhuanhong , Deng Weifen , Zhang Yaou , Wu Qiongfang 
Published: December 2022

AbstractEndometrium decidualization is a complex biological process, which includes the interplay of transcription factors, cytokines, cell cycle regulators, and other signaling pathways. However, the underlying molecular mechanisms of this process are not fully elucidated to date. In this study, we aimed to investigate the possible association between autophagy and recurrent implantation failure (RIF). A total of 81 genes were downregulated and 231 genes were upregulated in the RIF group compared with the control group, and the differences were statistically significant (p < 0.05). Further, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway were analyzed, and we found that some autophagy markers, for example, LC3‐II, LAMP2, and HIF‐1α were significantly increased, whereas P62 was drastically downregulated in the RIF group. Similar results were observed in proteins level; and the autophagy puncta were also markedly enhanced in the endometrial tissues of RIF patients. Autophagy is closely associated with the RIF occurs and may be involved in the pathogenesis of RIF.
Model‐constrained reconstruction accelerated with Fourier‐based undersampling for hyperpolarized [1‐13C] pyruvate imaging
Authors: Xu Zhan , Michel Keith A. , Walker Christopher M. , Harlan Collin J. , Martinez Gary V. , Gordon Jeremy W. , Chen Hsin‐Yu , Vigneron Daniel B. , Bankson James A. 
Published: December 2022

PurposeModel‐constrained reconstruction with Fourier‐based undersampling (MoReFUn) is introduced to accelerate the acquisition of dynamic MRI using hyperpolarized [1‐13C]‐pyruvate.MethodsThe MoReFUn method resolves spatial aliasing using constraints introduced by a pharmacokinetic model that describes the signal evolution of both pyruvate and lactate. Acceleration was evaluated on three single‐channel data sets: a numerical digital phantom that is used to validate the accuracy of reconstruction and model parameter restoration under various SNR and undersampling ratios, prospectively and retrospectively sampled data of an in vitro dynamic multispectral phantom, and retrospectively undersampled imaging data from a prostate cancer patient to test the fidelity of reconstructed metabolite time series.ResultsAll three data sets showed successful reconstruction using MoReFUn. In simulation and retrospective phantom data, the restored time series of pyruvate and lactate maintained the image details, and the mean square residual error of the accelerated reconstruction increased only slightly (< 10%) at a reduction factor up to 8. In prostate data, the quantitative estimation of the conversion‐rate constant of pyruvate to lactate was achieved with high accuracy of less than 10% error at a reduction factor of 2 compared with the conversion rate derived from unaccelerated data.ConclusionThe MoReFUn technique can be used as an effective and reliable imaging acceleration method for metabolic imaging using hyperpolarized [1‐13C]‐pyruvate.
Introduction: Hopes of and for Whiteness
Authors: Jeske Christine 
Published: December 2022

AbstractThis article introduces and explores two intersections between hope and whiteness: first, how various forms of hope alternately operate as discursive techniques that reproduce or resist whiteness; and second, whether theorists have warrant to hope for changes in whiteness itself. In order to prompt further study of both, I survey literature to propose seven dimensions for comparing forms of hope. I then apply this incipient typology of hopes to ethnographic evidence of white people who relocated to live in predominantly Black neighborhoods. I argue that their modes of hope transformed to become less agentic, less optimistic, and less conformed to white supremacist modes of hope. I close with a reflexive look at the place of hope in whiteness studies itself, pointing to two possible foundations of hoping for better future possibilities of whiteness.
Outcomes of penile inversion vaginoplasty and robotic‐assisted peritoneal flap vaginoplasty in obese and nonobese patients
Authors: Acar Omer , Alcantar Jonathan , Millman Alexandra , Naha Ushasi , Cedeno Juan Diego , Morgantini Luca , Kocjancic Ervin 
Published: December 2022

AbstractAimTo explore the impact of body mass index (BMI) on the outcomes of gender‐affirming vaginoplasty.MethodsA cohort consisting of all gender‐affirming vaginoplasties in our practice between September 27th, 2018, and September 1st, 2022 were identified, and data were retrospectively collected. Patients were classified as obese if their BMI was ≥30 kg/m2 at the time of surgery and nonobese if their BMI was <30 kg/m2. Complications were assigned a Clavien–Dindo grade and grouped as Grade ≥2 versus Grade ≤1. Patient‐reported functional outcomes of intact erogenous sensation, tactile sensation, ability to achieve penetrative vaginal intercourse, and cosmetic satisfaction were assessed.ResultsA total of 58 patients with a mean follow‐up time of 6.9 months were included. Seventeen patients (mean BMI = 36.8 kg/m2) were classified as obese and 41 patients (mean BMI = 25.1 kg/m2) were classified as nonobese. No significant differences in outcomes were identified in the obese versus nonobese groups in terms of the incidence of complications. Patient‐reported functional outcomes did not differ significantly between the two groups.ConclusionsSimilar results can be achieved with gender‐affirming vaginoplasty in obese patients when compared to their nonobese counterparts. Eligibility for this procedure should not be restricted based on BMI alone.
Real‐time monitoring of enzyme‐catalyzed phosphoribosylation of anti‐influenza prodrug favipiravir by time‐lapse nuclear magnetic resonance spectroscopy
Authors: Sugiki Toshihiko , Ito Akihiro , Hatanaka Yuko , Tsukamoto Masaki , Murata Tsuyoshi , Miyanishi Koichiro , Kagawa Akinori , Fujiwara Toshimichi , Kitagawa Masahiro , Morita Yasushi , Negoro Makoto 
Published: December 2022

AbstractFavipiravir (brand name Avigan), a widely known anti‐influenza prodrug, is metabolized by endogenous enzymes of host cells to generate the active form, which exerts inhibition of viral RNA‐dependent RNA polymerase activity; first, favipiravir is converted to its phosphoribosylated form, favipiravir‐ribofuranosyl‐5′‐monophosphate (favipiravir‐RMP), by hypoxanthine‐guanine phosphoribosyltransferase (HGPRT). Because this phosphoribosylation reaction is the rate‐determining step in the generation of the active metabolite, quantitative and real‐time monitoring of the HGPRT‐catalyzed reaction is essential to understanding the pharmacokinetics of favipiravir. However, assay methods enabling such monitoring have not been established. 19F‐ or 31P‐based nuclear magnetic resonance (NMR) are powerful techniques for observation of intermolecular interactions, chemical reactions, and metabolism of molecules of interest, given that NMR signals of the heteronuclei sensitively reflect changes in the chemical environment of these moieties. Here, we demonstrated direct, sensitive, target‐selective, nondestructive, and real‐time observation of HGPRT‐catalyzed conversion of favipiravir to favipiravir‐RMP by performing time‐lapse 19F‐NMR monitoring of the fluorine atom of favipiravir. In addition, we showed that 31P‐NMR can be used for real‐time observation of the identical reaction by monitoring phosphorus atoms of the phosphoribosyl group of favipiravir‐RMP and of the pyrophosphate product of that reaction. Furthermore, we demonstrated that NMR approaches permit the determination of general parameters of enzymatic activity such as Vmax and Km. This method not only can be widely employed in enzyme assays, but also may be of use in the screening and development of new favipiravir‐analog antiviral prodrugs that can be phosphoribosylated more efficiently by HGPRT, which would increase the intracellular concentration of the drug's active form. The techniques demonstrated in this study would allow more detailed investigation of the pharmacokinetics of fluorinated drugs, and might significantly contribute to opening new avenues for widespread pharmaceutical studies.
Two new mixed‐integer programming models for the integrated train formation and shipment path optimization problem
Authors: Arsalani Pouria , Reisi‐Nafchi Mohammad , Dardashti Vahid , Moslehi Ghasem 
Published: December 2022

AbstractRailcars are known as the heart of the freight rail transportation industry. Hence, any improvements in their operations can lead to sharp reductions in various operating costs. One of the most critical operations on railcars is blocking and routing their transportation. Railway companies face continuous challenged about what blocks should be formed to carry shipments across different origin–destination pairs (O–D pairs) and reclassify them in intermediate yards to minimize transportation reclassification costs. In addition, it is necessary to determine train service between O–D pairs and the number of trains. Along with the shipment routing plans, this problem is called train formation and shipment path optimization (TFSP). In TFSP, some substructure and rail network operational constraints should be considered, including link capacity, classification capacity, the number of sorting tracks, and path length. This paper presents two arc‐based mixed‐integer linear programming (MILP) models to formulate the TFSP problem. To the best of the authors' knowledge, no MILP arc‐based model has been published for the problem that does not need any preprocess before solving. Computational results of solving models on the datasets showed that the first model could obtain a feasible solution with a maximum 0.05% gap up to 48 yards instance. The second model also could find a solution with a small gap compared to the optimal solution in a reasonable time for instances up to 128 yards. Also, the proposed models were compared to the best methods in the literature, and their superiority was shown.
Validity and reliability of an android device for the assessment of fall risk in older adult inmates
Authors: Vera‐Remartínez Enrique J. , Lázaro‐Monge Rocío , Casado‐Hoces Sofía V. , Garcés‐Pina Elena , Molés‐Julio María Pilar 
Published: December 2022

AbstractAimTo validate the Android device, FallSkip, as a tool to assess the fallers in older adult inmates.DesignA cross‐sectional descriptive and analytical study.MethodsFor the validation of the FallSkip, the diagnostic criterion used was the risk of having suffered a fall during the last year.ResultsThe results for the FallSkip tool were as follows: sensitivity 60.7%; specificity 83.0%; positive predictive value 65.4%; negative predictive value 80.0%; accuracy 75.3%. In total, 32.1% of participants were found to be at high risk of falls, 23.5% were at mild risk and 7.4% were found to have no risk.ConclusionThe FallSkip device is shown to be a very suitable tool for fall risk assessment. The sample studied presented a statistically significant percentage of fall risk, which made it necessary to carry out interventions through physical activities to improve balance and stability.
Should I Care or Should I Work? The Impact of Work on Informal Care
Authors: Carrino Ludovico , Nafilyan Vahé , Avendano Mauricio 
Published: December 2022

AbstractThis paper provides novel evidence on how a sharp increase in labor force participation among older women affects the provision of informal care to their older parents. Based on data from Understanding Society – The UK Household Longitudinal Study, we use an instrumental variable approach that exploits a unique reform that increased the female State Pension age by up to six years. Our results provide evidence of a trade‐off between the intensive margin of work and informal care provided outside the household: an increase of 10 hours of work per week reduces the provision of informal care by 2.1 hours a week, which amounts to roughly £2,100 of yearly care‐hours lost. This reduction in caregiving is largest among women working in physically or psychosocially demanding jobs, and “sandwich generation” women who have both a living grandchild and a parent alive. Using data from the English Longitudinal Study of Ageing, we show that older parents whose daughters became ineligible to claim their pensions experienced a significant reduction in the amount of care they receive from their daughters, which was not compensated by an increase in formal care or other sources of support. Our results suggest that policies that increase older workers’ labor supply require changes in long‐term care policy that compensate for the loss of informal care.
Toughening effect of thermoplastic polyurethane elastomer on the properties of fly ash‐reinforced polypropylene‐based composites
Authors: Ez‐Zahraoui Siham , Sabir Salma , Berchane Sabah , Bouhfid Rachid , Qaiss Abou El Kacem , Semlali Aouragh Hassani Fatima‐Zahra , El Achaby Mounir 
Published: December 2022

AbstractIn general, particulate reinforcement is known to greatly enhance the polymer composite rigidity at the expense of its ductility. Therefore, careful addition of elastomers can restore the composites toughness without sacrificing their stiffness. Thus, this work investigates the effect of TPU elastomer (thermoplastic polyurethane) on the ductile character of fly ash‐reinforced polypropylene (PP) composites. First, fly ash powder with particle‐size less than 63 μm (FA) was analyzed in terms of its physico‐chemical properties. The as‐characterized FA fine powder was then incorporated into PP polymer matrix to produce 50/50 wt% PP/FA masterbatch using extrusion process. Thereafter, the as prepared masterbatch was used to elaborate three polymer composite series by modifying the amount of FA and TPU via injection molding process. Binary and ternary PP composites filled with 5, 10, 15, and 20 wt% of FA or 80%FA/20%TPU or 50%FA/50%TPU were successfully manufactured. The resulted composites series were characterized in terms of their structural, morphological, thermal, and mechanical properties. It was found that the addition of FA into PP composites improved the composites' rigidity but reduced their ductility, due to the high reinforcing ability of FA particles. However, the inclusion of TPU to the binary PP/FA system exhibited a beneficial effect for restoring the ductility without a dramatic loss in stiffness, due to the toughening effect of TPU elastomer and improved interfacial adhesion. Overall, the above results suggest that a balance between the ratios of rigid particles and elastomer in a polymer matrix produces a multiphase polymer system with optimal mechanical performance, which make them promising materials for engineering applications.
Geographical and seasonal phytochemical variation of Artemisia afra Jacq. ex Willd
Authors: Olivier Duné , van der Kooy Frank , Gerber Minja 
Published: December 2022

AbstractIntroductionArtemisia afra Jacq. ex. Willd. (Asteraceae) is a popular traditional medicine in South Africa, mainly used in the form of an infusion, for the treatment of respiratory ailments. Quality control methods are limited and phytochemical variation for the infusion is not well known.ObjectiveTo develop a sensitive quality control method for A. afra infusions by validating a liquid chromatography electrospray ionisation tandem mass spectrometry (LC‐ESI‐MS/MS) method and quantitatively comparing six marker compounds in A. afra samples collected from different locations and over a 12‐month period.Material and methodsThere was a multiple reaction monitoring method optimised and validated, according to ICH and FDA guidelines, to quantify the chemical markers present in infusions.ResultsThe chemistry differed significantly and interestingly, with an interchangeable trend between chlorogenic acid (CGA) and 4,5‐dicaffeoylquinic acid (DCQA) observed in the samples collected monthly, elevated levels of CGA during winter and elevated levels of DCQA during summer. The remaining four markers showed a steady decrease as winter approached and a steady increase as summer approached. The ranges of the six markers were the following: CGA (0.68–14.68 μg/mg), DCQA (0.005–8.110 μg/mg), quercetin (0.01–0.65 μg/mg), luteolin (0.05–1.30 ng/mg), scopoletin (0.10–1.14 μg/mg), scopolin (0.03–1.21 μg/mg).ConclusionsA sensitive LC‐ESI‐MS/MS method was developed, validated, and used to quantify six marker compounds. The results indicated a large degree of phytochemical variation occurred across all samples tested, which highlights the importance of producing herbal medicine under controlled conditions and the necessity of analytical quality control methods.
Presence of fetal DNA in maternal exhaled breath condensate
Authors: Tıplamaz Sıtkı , Eyüboğlu İrem Peker , Ünal Canan , Soyer Özge , Beksaç Mehmet Sinan , Akkiprik Mustafa 
Published: December 2022

AbstractObjectivesCell‐free DNA has been found in all body fluids, but DNAs emerging from locations that are not in direct contact with breath in exhaled breath condensate (EBC) are yet to be found. The potential of EBC for prenatal and cancer screening prompted us to investigate whether fetal DNA is present in maternal EBC.MethodA total of 20 pregnant women's EBC and blood samples were collected. Four Y chromosome‐specific assays were tested on all EBC and plasma samples by quantitative PCR (qPCR). The best‐performing assay was used for digital droplet PCR (ddPCR) on all EBC and the six plasma samples.ResultsThe sex of the fetuses was accurately determined from plasma samples. DNA sequences could not be properly amplified in EBC samples by the qPCR. By ddPCR, the Y chromosome sequence was amplified in two of the 11 EBC samples, from women carrying male fetuses (2/11), and the Y chromosome sequence was not amplified in the EBC of women carrying female fetuses (9/9). Exhaled breath condensate ddPCR result's specificity was 100%, the detection rate of Y chromosome was 18.18% (2/11), and the corrected accuracy was 59.09%.ConclusionOur finding of “the presence of fetal DNA in maternal EBC”, despite the low detection rate, might have a major impact on prenatal diagnosis and cancer screening.
Prospective validation of a dynamic prognostic model for identifying COVID‐19 patients at high risk of rapid deterioration
Authors: Lin Kueiyu Joshua , D'Andrea Elvira , Desai Rishi J. , Gagne Joshua J. , Liu Jun , Wang Shirley V. 
Published: December 2022

AbstractBackgroundWe sought to develop and prospectively validate a dynamic model that incorporates changes in biomarkers to predict rapid clinical deterioration in patients hospitalized for COVID‐19.MethodsWe established a retrospective cohort of hospitalized patients aged ≥18 years with laboratory‐confirmed COVID‐19 using electronic health records (EHR) from a large integrated care delivery network in Massachusetts including >40 facilities from March to November 2020. A total of 71 factors, including time‐varying vital signs and laboratory findings during hospitalization were screened. We used elastic net regression and tree‐based scan statistics for variable selection to predict rapid deterioration, defined as progression by two levels of a published severity scale in the next 24 h. The development cohort included the first 70% of patients identified chronologically in calendar time; the latter 30% served as the validation cohort. A cut‐off point was estimated to alert clinicians of high risk of imminent clinical deterioration.ResultsOverall, 3706 patients (2587 in the development and 1119 in the validation cohort) met the eligibility criteria with a median of 6 days of follow‐up. Twenty‐four variables were selected in the final model, including 16 dynamic changes of laboratory results or vital signs. Area under the ROC curve was 0.81 (95% CI, 0.79–0.82) in the development set and 0.74 (95% CI, 0.71–0.78) in the validation set. The model was well calibrated (slope = 0.84 and intercept = −0.07 on the calibration plot in the validation set). The estimated cut‐off point, with a positive predictive value of 83%, was 0.78.ConclusionsOur prospectively validated dynamic prognostic model demonstrated temporal generalizability in a rapidly evolving pandemic and can be used to inform day‐to‐day treatment and resource allocation decisions based on dynamic changes in biophysiological factors.