bluuebunny/crossref_metadata_2025_split huggingface dataset:
An efficient selection producing structural gene mutants of yeast alcohol dehydrogenase resistant to pyrazole.
Authors: Wills C , Hom D 
Published: January 2021

Abstract
Selection for resistance to allyl alcohol in respiration-incompetent Saccharomyces cerevisiae produces a high proportion of mutants that can be localized within the ADH2 structural gene and that still, because of the type of selection employed, retain enzyme activity. We show here that a similar type of selection produces a similarly high proportion of mutants resistant to the competitive inhibitor pyrazole. The first four mutants examined, picked at random from a collection of spontaneous pyrazole-resistant mutants, show altered--usually increased--KM values for ethanol and NAD+, and markedly increased K1 values for pyrazole, compared with the wild type. When these kinetic measures and their electrophoretic mobilities were compared, all the mutants could be clearly distinguished from each other as well as from wild type. Genetic analysis shows these mutants to be close to and probably resident in the structural gene. For a variety of reasons, these mutants are even more favorable subjects for population genetic analysis and the dissection of molecular microevolution than are allyl alcohol-resistant mutants.
Adaptation at specific loci. V. Metabolically adjacent enzyme loci may have very distinct experiences of selective pressures.
Authors: Carter P A , Watt W B 
Published: January 2021

Abstract
The polymorphic phosphoglucomutase (PGM) and glucose-6-phosphate dehydrogenase (G6PD) loci have been studied in parallel to experimental work on the phosphoglucose isomerase (PGI) polymorphism in Colias butterflies. PGI, PGM and G6PD are also autosomal in Colias. PGM and G6PD are loosely linked (and represent the first identified autosomal linkage group in Colias); they assort independently from PGI. Recombination occurs in both sexes. Neither PGM nor G6PD shows large, consistent differences in flight capacity through the day among its genotypes, as PGI does. PGM shows some change of allele frequencies, and match to Hardy-Weinberg expectation, with air temperature in middle and latter parts of the season, but not early in the season. G6PD may show some heterozygote excess over Hardy-Weinberg expectation early in the day, but more testing is needed. No evidence for differential survivorship was seen at PGM or G6PD, in contrast to PGI. At the PGM and G6PD loci, male heterozygotes are advantaged in mating with females, but without the evidence of female choice which occurs for PGI. These effects are not correlated among the three loci. There is no assortative mating at G6PD (nor at PGI). There is minor positive assortative mating of PGM heterozygotes, but it is too weak to account for the PGM-genotype-specific male mating advantage. No trends of multilocus genotype frequencies involving PGI are seen. Certain PGM-G6PD two-locus genotypes are over-represented, and others under-represented, in wild adult samples, particularly among males and uniformly among successfully mating males. Our results emphasize that enzyme loci sharing a substrate need not have common experience of the existence or strength of natural selection, and suggest initial food-resource processing and allocation as a possible context for fitness-related effects of the PGM and G6PD polymorphisms.
Heterochronic mutations affecting shoot development in maize.
Authors: Poethig R S 
Published: January 2021

Abstract
Three semidominant, nonallelic mutations of maize, Teopod 1 (Tp1), Teopod 2 (Tp2) and Teopod 3 (Tp3), have a profound effect on both vegetative and reproductive development. Although each mutation is phenotypically distinct, they all (1) increase the number of vegetative phytomers; (2) increase the number of phytomers producing ears, tillers and prop roots; (3) increase the number of leaves bearing epidermal wax; (4) decrease the size of leaves and internodes; (5) decrease the size of both the ear and tassel; and (6) transform reproductive structures into vegetative ones. The analysis presented here suggests that this phenotype reflects the prolonged expression of a juvenile, vegetative developmental program which overlaps with the reproductive developmental program. The expression of these mutations is different in each of the four inbred backgrounds used in this study. Tp1 and Tp2 have similar phenotypes and are more highly expressed in the A632 and Oh51a inbred backgrounds than in W23 and Mo17. Tp3 has less extreme effects than either of these mutations and has the opposite modification pattern; i.e., it is more highly expressed in W23 and Mo17 than in A632 and Oh51a. The expression of Tp1 and Tp2 in the presence of varying doses of their wild-type alleles indicate that both are gain-of-function mutations. The phenotypes of Tp1 and Tp2 and the nature of their response to variation in gene dose suggest that they control related, but nonidentical functions. The developmental and evolutionary implications of the heterochronic phenotype of these mutations is discussed.
Developmental genetics of chromosome I spermatogenesis-defective mutants in the nematode Caenorhabditis elegans.
Authors: L'Hernault S W , Shakes D C , Ward S 
Published: January 2021

Abstract
Mutations affecting Caenorhabditis elegans spermatogenesis can be used to dissect the processes of meiosis and spermatozoan morphological maturation. We have obtained 23 new chromosome I mutations that affect spermatogenesis (spe mutations). These mutations, together with six previously described mutations, identify 11 complementation groups, of which six are defined by multiple alleles. These spe mutations are all recessive and cause normally self-fertile hermaphrodites to produce unfertilized oocytes that can be fertilized by wild-type male sperm. Five chromosome I mutation/deficiency heterozygotes have similar phenotypes to the homozygote showing that the probable null phenotype of these genes is defective sperm. Spermatogenesis is disrupted at different steps by mutations in these genes. The maturation of 1 degree spermatocytes is disrupted by mutations in spe-4 and spe-5. Spermatids from spe-8 and spe-12 mutants develop into normal spermatozoa in males, but not in hermaphrodites. fer-6 spermatids are abnormal, and fer-1 spermatids look normal but subsequently become abnormal spermatozoa. Mutations in five genes (fer-7, spe-9, spe-11, spe-13 and spe-15) allow formation of normal looking motile spermatozoa that appear to be defective in either sperm-spermathecal or sperm-oocyte interactions.
Organization of the Tgm family of transposable elements in soybean.
Authors: Rhodes P R , Vodkin L O 
Published: January 2021

Abstract
We have compared the organization of six Tgm elements that were selected from a genomic library of soybean DNA on the basis of hybridization with subcloned regions of Tgm 1 (transposon, Glycine max) from the seed lectin gene. These elements ranged in size from 1.6 kbp to greater than 12 kbp. Tgm2, Tgm3, Tgm4 and Tgm5 represent partial isolates in which the genomic clone contained a 3' but not a 5' terminus of the element; while Tgm6 and Tgm7, like Tgm1, were small isolates flanked by both 5' and 3' nonelement sequences. Cross-hybridization studies between subcloned portions of these seven elements identified regions of homology which suggest that the Tgm transposable elements of soybean form a family of deletion derivatives. In addition to internal deletion events, numerous deletions and base substitutions are also present within the borders of these elements which are comprised of the same tandemly repeated sequence. The 39% amino acid homology between a 1 kb portion of an open reading frame in Tgm4 and Tgm5 and ORF1, an open frame from the first intron of the maize Enhancer (Suppressor-mutator) transposable element, suggests that both elements encode a common function that requires a high degree of protein conservation.
Chronic Exposure to Cadmium Induces Differential Methylation in Mice Spermatozoa
Authors: Saintilnord Wesley N , Tenlep Sara Y N , Preston Joshua D , Duregon Eleonora , DeRouchey Jason E , Unrine Jason M , de Cabo Rafael , Pearson Kevin J , Fondufe-Mittendorf Yvonne N 
Published: January 2021

Abstract
Cadmium exposure is ubiquitous and has been linked to diseases including cancers and reproductive defects. Since cadmium is nonmutagenic, it is thought to exert its gene dysregulatory effects through epigenetic reprogramming. Several studies have implicated germline exposure to cadmium in developmental reprogramming. However, most of these studies have focused on maternal exposure, while the impact on sperm fertility and disease susceptibility has received less attention. In this study, we used reduced representation bisulfite sequencing to comprehensively investigate the impact of chronic cadmium exposure on mouse spermatozoa DNA methylation. Adult male C57BL/J6 mice were provided water with or without cadmium chloride for 9 weeks. Sperm, testes, liver, and kidney tissues were collected at the end of the treatment period. Cadmium exposure was confirmed through gene expression analysis of metallothionein-1 and 2, 2 well-known cadmium-induced genes. Analysis of sperm DNA methylation changes revealed 1788 differentially methylated sites present at regulatory regions in sperm of mice exposed to cadmium compared with vehicle (control) mice. Furthermore, most of these differential methylation changes positively correlated with changes in gene expression at both the transcription initiation stage as well as the splicing levels. Interestingly, the genes targeted by cadmium exposure are involved in several critical developmental processes. Our results present a comprehensive analysis of the sperm methylome in response to chronic cadmium exposure. These data, therefore, highlight a foundational framework to study gene expression patterns that may affect fertility in the exposed individual as well as their offspring, through paternal inheritance.
Patterns of Approach to Activity in 851 Patients With Severe Chronic Pain
Authors: Titze Christina , Hasenbring Monika I. , Kristensen Lotte , Bendix Laila , Vaegter Henrik B. 
Published: January 2021

Objectives:
The Avoidance-Endurance Fast-Screen (AEFS) is a 9-item self-report questionnaire that classifies patients with back pain into 4 activity-related subgroups, based on the Avoidance-Endurance Model of pain. The objective of this study was to translate the AEFS into Danish and investigate its discriminative abilities in a large, diverse patient sample.

Materials and Methods:
A total of 851 specialist care-seeking patients with severe chronic pain conditions participated in this cross-sectional study. Participants were categorized as showing a “distress-endurance” (DER), “eustress-endurance” (EER), “fear-avoidance” (FAR), or “adaptive” (AR) pattern. Principal component analysis reduced a large number of psychological variables beforehand. Construct and outcome-based validity were explored using multivariate analysis of variance.

Results:
Of the participants, 33.6% were categorized as DER, 29.4% as EER, 22% as FAR, and 15% as adaptive. Principal component analysis showed the factors activity-related pain behavior, affective distress, and dysfunctional pain thoughts. The AEFS-DK discriminated all 4 subgroups in terms or their pain behavior with EER>DER>AR>FAR. FAR showed less moderate/vigorous activity than DER and EER and more sedentary time than EER. DER and FAR showed higher affective distress, dysfunctional pain thoughts, and poorer outcomes than AR and EER.

Conclusion:
The results indicate good construct validity of the AEFS-DK discriminating the 4 avoidance-endurance model-related subgroups with respect to approach to activity behavior, psychological variables, and reported physical activity. Concerning outcome-based validity, 2 subgroups DER/FAR and AR/EER could be distinguished with inconclusive results for the eustress-endurance subgroup. Future studies are warranted using longitudinal research designs investigating whether AEFS subgroups differ in terms of treatment effects and long-term prognosis.
Evaluating Social Media Use Among Active American Members of the Cervical Spine Research Society
Authors: Bernstein David N. , Melone Giresse , Jubril Ayodeji , Zhang Jun , Mesfin Addisu 
Published: January 2021

Study Design:
Observational study.

Objectives:
The objectives of this study are (1) to quantify social media use among active American Cervical Spine Research Society (CSRS) members; (2) to determine if there is an association between practice setting, region, or years of active membership and social media use.

Summary of Background Data:
Many patients now seek health and physician information online, including on social media. Indeed, social media use by orthopedic surgeons has been shown to be associated with more and improved ratings on physician review websites. Further, social media can provide a means for improved doctor-patient relationships, educational endeavors, and professional networking. However, there is a paucity of literature examining social media use among spine surgeons.

Materials and Methods:
In January 2019, the CSRS membership directory was used to identify all active American spine surgeon members. Through a Google search, social media use of each spine surgeon on the following platforms was identified: provider page/official website; Facebook; Twitter; Instagram; LinkedIn; and YouTube. In addition, surgeon characteristics were recorded. The percentage of spine surgeons using each social media platform was reported. Bivariate analysis was used to compare social media use by practice setting, region, and years of active CSRS membership.

Results:
Nearly all spine surgeons have a provider page/official website (98%) and over half (56%) have a LinkedIn presence. Less than one third of spine surgeons are on any of the remaining social media platforms analyzed. The least frequently used social media platform was Instagram (3.2%). There was no difference in any social media platform use by practice setting, region, and years of active CSRS membership.

Conclusions:
As social media becomes even more common place and the role of it in medical care continues to be better defined, there is notable room for increased social media use among active American members of the CSRS.

Level of Evidence:
Level IV—observational study.
Non‐invasive Predictors of Esophageal Varices With a High Risk of Bleeding in Pediatric Cirrhotic Patients
Authors: Lopes José Ricardo Borém , Ferreira Alexandre Rodrigues , Liu Priscila Menezes Ferri , Queiroz Thaís Costa Nascentes , Fagundes Eleonora Druve Tavares , Pimenta Júlio Rocha , Neto José Andrade Franco , Carvalho Simone Diniz , Borges Maria Eduarda Marques , Colin Lucas Garcia de Figueiredo 
Published: January 2021

ABSTRACTObjectives:To evaluate non‐invasive predictive factors of varices with a high risk of bleeding in pediatric cirrhotic patients.Methods:This retrospective, cross‐sectional study included data from 158 children with cirrhosis, median age of 5.38 years (interquartile [IQ] 2.08−11.52 years), and no history of upper gastrointestinal bleeding. Patients underwent an endoscopy to screen for esophageal varices. Varices with a high risk of bleeding were defined as those with a medium to large caliber, presence of red spots, or the presence of gastric varices and identified as high‐risk varices (HRV). Laboratory and clinical factors were evaluated as possible predictors of HRV.Results:HRV were detected in 30 children (19%) after the first endoscopy. In the multivariate analysis, only the risk score (RS), as described by Park et al, and the aspartate aminotransferase‐to‐platelet ratio index (APRi) were predictive of HRV. The best non‐invasive predictor of HRV was the RS with an area under the receiver operating characteristic curve of 0.764. When used a cut‐off point of −1.2, the sensitivity of the RS was 90% and specificity was 53%. The use of RS or APRi correctly identified 96% of children with HRV.Conclusions:The described predictors allow the correct identification of patients with HRV. The association of RS >−1.2 or APRi >1.4 has a good sensitivity to identify HRV and to prevent unnecessary endoscopy in about one‐third of children with no HRV.
Performance of a True Point-of-Care Assay for HIV-1/2 Viral Load Measurement at Antenatal and Postpartum Services
Authors: Meggi Bindiya , Bollinger Timothy , Zitha Alcina , Mudenyanga Chishamiso , Vubil Adolfo , Mutsaka Dadirayi , Nhachigule Carina , Mabunda Nedio , Loquiha Osvaldo , Kroidl Arne , Jani Ilesh V. 
Published: January 2021

Background:
Timely viral load (VL) results during pregnancy and the postpartum period are crucial for HIV disease management and for preventing mother-to-child transmission. Point-of-care (POC) VL testing could reduce turnaround times and streamline patient management. We evaluated the diagnostic performance of the novel m-PIMA HIV-1/2 VL assay (Abbott, Chicago, IL) in Mozambique.

Setting:
The study was conducted in prenatal and postpartum consultation rooms in 2 primary health care clinics. Sample collection and testing on m-PIMA were performed by trained nurses.

Methods:
HIV-infected pregnant and postpartum women on antiretroviral treatment (ART) or ART naive were tested using both on-site m-PIMA POC and referral laboratory-based real-time VL assays. Linear regression analysis and Bland–Altman plots were used to calculate the agreement between both.

Findings:
Correlation between venous blood plasma POC and plasma laboratory-based VL was strong (r2 = 0.850, P < 0.01), with good agreement between the methods [overall bias 0.202 log copies/mL (95% CI: 0.366 to 0.772 log copies/mL)]. Using the threshold of 1000 copies/mL, which is used to determine ART failure, the sensitivity and specificity of the POC VL assay were 95.0% (95% CI: 91.6% to 97.3%) and 96.5% (95% CI: 94.2% to 98.0%), respectively. The correlation coefficient between the venous and capillary sample types was 0.983 (r2 = 0.966).

Conclusions:
On-site, nurse-performed POC VL testing is feasible and accurate in resource-limited primary health care settings. The operational challenge of plasma separation within clinics for POC testing was successfully overcome using minicentrifuges. The use of capillary blood could simplify the execution of the assay in a clinical environment.
Alzheimer’s genetic risk effects on cerebral blood flow are spatially consistent and proximal to gene expression across the lifespan
Authors: Chandler H.L , Wise R.G , Linden D.E , Williams J , Murphy K , Lancaster T.M ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: January 2021

AbstractCerebrovascular dysregulation is a hallmark feature of Alzheimer’s disease (AD), where alterations in cerebral blood flow (CBF) are observed decades prior to symptom onset. Genome-wide association studies (GWAS) show that AD has a polygenic aetiology, providing a tool for studying AD susceptibility across the lifespan. Here, we ascertain whether AD genetic risk effects on CBF previously observed (Chandler et al., 2019) remain consistent across the lifespan. We further provide a causal mechanism to AD genetic risk scores (AD-GRS) effects by establishing spatial convergence between AD-GRS associated regional reductions in CBF and mRNA expression of the proximal AD transcripts using independent data from the Allen Brain Atlas. We analysed grey matter (GM) CBF in a young cohort (N=75; aged 18-35) and an older cohort (N=90; aged 55-85). Critically, we observed that AD-GRS was negatively associated with whole brain GM CBF in the older cohort (standardised β −0.38 [−0.68 – −0.09], P = 0.012), consistent with our prior observation in younger healthy adults (Chandler et al., 2019). We then demonstrate that the regional impact of AD-GRS on GM CBF was spatially consistent across the younger and older samples (r = 0.233, P = 0.035). Finally, we show that CBF across the cortex was related to the regional expression of the genes proximal to SNP’s used to estimate AD-GRS in both younger and older cohorts (ZTWO-TAILED= −1.99, P= 0.047; ZTWO-TAILED= −2.153 P = 0.032, respectively). These observations collectively demonstrate that AD risk alleles have a negative influence on brain vascular function and likely contribute to cerebrovascular changes preceding the onset of clinical symptoms, potentially driven by regional expression of proximal AD risk genes across the brain. Our observations suggest that reduced CBF is an early antecedent of AD and a key modifiable target for therapeutic intervention in individuals with a higher cumulative genetic risk for AD. This study will further enable identification of key molecular processes that underpin AD genetic risk related reductions in CBF that could be targeted decades prior to the onset of neurodegeneration.
Predicting Stroke and Mortality in Mitral Regurgitation: A Gradient Boosting Approach
Authors: Zhou Jiandong , Lee Sharen , Liu Yingzhi , Liu Tong , Tse Gary , Zhang Qingpeng 
Published: January 2021

AbstractIntroductionWe hypothesized that an interpretable gradient boosting machine (GBM) model considering comorbidities, P-wave and echocardiographic measurements, can better predict mortality and cerebrovascular events in mitral regurgitation (MR).MethodsPatients from a tertiary center were analyzed. The GBM model was used as an interpretable statistical approach to identify the leading indicators of high-risk patients with either outcome of CVAs and all-cause mortality.ResultsA total of 706 patients were included. GBM analysis showed that age, systolic blood pressure, diastolic blood pressure, plasma albumin levels, mean P-wave duration (PWD), MR regurgitant volume, left ventricular ejection fraction (LVEF), left atrial dimension at end-systole (LADs), velocity-time integral (VTI) and effective regurgitant orifice were significant predictors of TIA/stroke. Age, sodium, urea and albumin levels, platelet count, mean PWD, LVEF, LADs, left ventricular dimension at end systole (LVDs) and VTI were significant predictors of all-cause mortality. The GBM demonstrates the best predictive performance in terms of precision, sensitivity c-statistic and F1-score compared to logistic regression, decision tree, random forest, support vector machine, and artificial neural networks.ConclusionGradient boosting model incorporating clinical data from different investigative modalities significantly improves risk prediction performance and identify key indicators for outcome prediction in MR.
Hydroxyzine inhibits SARS-CoV-2 Spike protein binding to ACE2 in a qualitativein vitroassay
Authors: Rivas Maria Dolores , Saponi-Cortes Jose Maria Rafael , Zamorano Jose 
Published: January 2021

AbstractCOVID-19 currently represents a major public health problem. Multiple efforts are being performed to control this disease. Vaccinations are already in progress. However, no effective treatments have been found so far. The disease is caused by the SARS-CoV-2 coronavirus that through the Spike protein interacts with its cell surface receptor ACE2 to enter into the host cells. Therefore, compounds able to block this interaction may help to stop disease progression. In this study, we have analyzed the effect of compounds reported to interact and modify the activity of ACE2 on the binding of the Spike protein. Among the compounds tested, we found that hydroxyzine could inhibit the binding of the receptor-binding domain of Spike protein to ACE2 in a qualitativein vitroassay. This finding supports the reported clinical data showing the benefits of hydroxyzine on COVID-19 patients, raising the need for further investigation into its effectiveness in the treatment of COVID-19 given its well-characterized medical properties and affordable cost.