bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ehlers–Danlos syndrome type IV with a novel COL3A1 exon 14 skipping variation confirmed by Tohoku Medical Megabank Organization genomic database
Authors: Shido Kosuke , Kojima Kaname , Yoshida‐Akai Saaya , Kikuchi Katsuko , Hatamochi Atsushi , Aiba Setsuya , Yamasaki Kenshi 
Published: August 2021

AbstractA novel COL3A1 variant was identified in a Japanese case of Ehlers–Danlos syndrome type IV (EDS‐IV) with a characteristic “Madonna” face, fragile uterus, and easy bruising in addition to a history of cavernous sinus fistula. We confirmed variable diameters of collagen fibrils in the dermis and decrease in type 3 collagen production from cultured fibroblasts. Genomic DNA sequencing of the COL3A1 region and COL3A1 cDNA sequence expressing in cultured fibroblasts identified that a nucleotide variation at c.951+2T>G on intron 14 leads to skipping of exon 14 in COL3A1 cDNA. The novel variation in the splice site of COL3A1 region g.IVS14+2T>G was not listed in the EDS‐IV pathogenic genetic databases including Human Gene Mutation Database, ClinVar, and Leiden Open Variation Database. Using the whole genome sequence database of 8380 Japanese individuals reported by the Tohoku Medical Megabank Organization (ToMMo) cohort study, we also confirmed that COL3A1 g.IVS14+2T>G was not a common single nucleotide variation in the Japanese population, although 13 EDS‐related COL3A1 variants were identified in the ToMMo database of 8380 Japanese individuals. These results demonstrated that our case of EDS‐IV was a result of the novel variation of COL3A1 g.IVS14+2T>G. These statistical genetics approaches with the combination of the ToMMo database of 8380 Japanese individuals and pathogenic genetic databases are a useful method to confirm the uniqueness of novel variation in Japanese.
Sustained efficacy and safety of guselkumab in patients with palmoplantar pustulosis through 1.5 years in a randomized phase 3 study
Authors: Okubo Yukari , Morishima Hitomi , Zheng Richuan , Terui Tadashi 
Published: August 2021

AbstractThe safety and efficacy of guselkumab for palmoplantar pustulosis (PPP) have been established through week (W)52; however, no sufficient information is available beyond 1 year. This study was conducted to assess the efficacy and safety of guselkumab through W84, and to explore factors associated with the sustainability of its efficacy in Japanese PPP patients. Patients received guselkumab 100 or 200 mg at W0, W4, W12, and every 8 weeks (q8w) until W60, or placebo at W0, W4, and W12. At W16, patients receiving placebo were re‐randomized to receive guselkumab 100/200 mg at W16, W20, and q8w until W60. Efficacy end‐points included PPP Area and Severity Index (PPPASI), PPP Severity Index (PPSI), Physician’s Global Assessment scores, and patient reported outcomes (PRO) (Dermatology Life Quality Index, EuroQoL‐5 Dimensions, and 36‐item Short Form Health Survey). Post‐hoc comparison of patient characteristics was performed between PPPASI‐75/90 responders and non‐responders at W60, and sustained responders and non‐responders at W84. Safety was evaluated through W84. A total of 45, 43, 21, and 24 patients from the guselkumab 100 mg, guselkumab 200 mg, placebo→guselkumab 100 mg, and placebo→guselkumab 200 mg groups, respectively, completed the study through W84. Overall, the mean improvement in the guselkumab groups from baseline in the PPPASI and PPSI total scores at W84 was ~79% and ~66%, respectively. All PRO improved through W84. The proportion of responders through W60 was higher in patients who had not received prior phototherapy and non‐biologic systemic therapy for PPP. Non‐smokers and patients with no prior non‐biologic systemic treatment tended numerically towards sustained efficacy through W84. The majority of treatment‐emergent adverse events (TEAE) were mild to moderate (~88%) with low incidence of serious TEAE (7.6%). Overall, guselkumab showed sustained efficacy and safety with improvement in the health‐related quality of life through W84 in Japanese PPP patients.
Barriers to restoration: Pollution alters nurse effects for an ecosystem engineer
Authors: Cameron Hayley , Amor Michael D. , Bellgrove Alecia 
Published: August 2021

Abstract

Nurse plants modify the environment beneath their canopies to create favourable habitats for propagule recruitment. Nurse plants are potentially valuable tools for ecological restoration—yet empirical tests, particularly in polluted environments, remain rare.

The few studies that do exist find that nurse plants positively affect propagule recruitment in polluted environments. Yet most tests have focused on pollution‐tolerant species in metal‐contaminated environments. Biotic interactions are highly context dependent, however, such that extrapolations to other suites of species and pollutant types appear premature.

We examined changes in intraspecific nurse effects across pollution regimes for a pollution‐sensitive, macroalgal ecosystem engineer that is a target for intertidal restoration. In a manipulative field experiment, we out‐planted propagules in the presence and absence of conspecific canopies at unpolluted control shores and shores that received a partly remediated (low‐toxicity) sewage effluent. We then monitored the performance (survival and growth) of these propagules over time.

Algal canopies facilitated the survival and early growth of propagules at control sites, but not at partially remediated sites where propagules performed poorly irrespective of canopy presence.

Synthesis and applications. Using a pollution‐sensitive, macroalgal ecosystem engineer, we show for the first time that nurse‐plant effects can be contingent on pollution regime, and that exposure to pollution (even at low levels) can erode nurse effects. We caution that nurse plants are unlikely to be universal tools for ecological restoration, including systems where facilitative nurse effects naturally occur (in our case, macroalgal canopies on unpolluted rocky reefs). Management practitioners should carefully consider the disturbance (e.g. pollution) tolerance of target species, and test whether nurse effects are maintained under current disturbance regimes, before large‐scale translocations are attempted.
Feeding and Healing Bodies and Souls: German Women in Nursing, 1830s–1850s
Authors: Soine Aeleah 
Published: August 2021

AbstractNursing care of the 1830s−40s required significant financial stewardship, material resources, spiritual fortitude and political support alongside the everyday routines of cleaning, cooking and home visiting. The minutiae of Catholic, Protestant and other Prussian institutional donations, budgets and schedules, government records and occasionally women's own writings reveal how German nursing was not a singular and timeless profession. Rather, the feminisation of nursing emerged out of a myriad of gendered ways elite, bourgeois, religious and working women collectively cared for the poor and the sick even before bacteriology and maternalist women's movements transformed nursing in the late nineteenth century.
Creating hypo‐/nonallergenic wheat products using processing methods: Fact or fiction?
Authors: Gao Haoran , Jorgensen Rick , Raghunath Rajsri , Nagisetty Siddharth , Ng Perry K. W. , Gangur Venu 
Published: August 2021

AbstractWheat allergy is a potentiallylife‐threatening disease that affects millions of people around the world. Food processing has been shown to influence the allergenicity of wheat and other major foods. However, a comprehensive review evaluating whether or not food processing can be used to develop hypo‐/nonallergenic wheat products is unavailable. There were three objectives for this study: (1) to critically evaluate the evidence on the effect of fermentation, thermal processing, and enzyme or acid hydrolysis on wheat allergenicity so as to identify the potential for and challenges of using these methods to produce hypo‐/nonallergenic wheat products; (2) to identify the molecular effects of food processing needed to create such products; and (3) to map the concept questions for future research and development to produce hypo‐/nonallergenic wheat products. We performed literature research using PubMed and Google Scholar databases with various combinations of keywords to generate the data to accomplish these objectives. We found that: (1) food processing significantly modulates wheat allergenicity; while some methods can reduce or even abolish the allergenicity, others can create mega allergens; and (2) fermentation and enzymatic hydrolysis hold the most potential to create novel hypo‐/nonallergenic wheat products; however, preclinical validation and human clinical trials are currently lacking. We also identify five specific research concepts to advance the research to enable the creation of hypo‐/nonallergenic wheat products for application in food, medical, and cosmetic industries.
Whole‐genome sequencing of brown‐marbled grouper (Epinephelus fuscoguttatus) provides insights into adaptive evolution and growth differences
Authors: Yang Yang , Wang Tong , Chen Jingfang , Wu Lina , Wu Xi , Zhang Weiwei , Luo Jian , Xia Junhong , Meng Zining , Liu Xiaochun 
Published: August 2021

AbstractThe brown‐marbled grouper (Epinephelus fuscoguttatus) is an important species of fish in the coral reef ecosystem and marine aquaculture industry. In this study, a high‐quality chromosome‐level genome of brown‐marbled grouper was assembled using Oxford Nanopore technology and Hi‐C technology. The GC content and heterozygosity were approximately 42% and 0.35%, respectively. A total of 230 contigs with a total length of 1047 Mb and contig N50 of 13.8 Mb were assembled, and 228 contigs (99.13%) were anchored into 24 chromosomes. A total of 24,005 protein‐coding genes were predicted, among which 23,862 (99.4%) predicted genes were annotated. Phylogenetic analysis showed that brown‐marbled grouper and humpback grouper were clustered into one clade that separated approximately 11–23 million years ago. Collinearity analyses showed that there was no obvious duplication of large fragments between chromosomes in the brown‐marbled grouper. Genomes of the humpback grouper and giant grouper showed a high collinearity with that of the brown‐marbled grouper. A total of 305 expanded gene families were detected in the brown‐marbled grouper genome, which is mainly involved in disease resistance. In addition, a genetic linkage map with 3061.88 cM was constructed. Based on the physical and genetic map, one growth‐related quantitative trait loci was detected in 32,332,447 bp of chromosome 20, and meox1 and etv4 were considered candidate growth‐related genes. This study provides pivotal genetic resources for further evolutionary analyses and artificial breeding of groupers.
Comprehensive expressional analysis of chemosensitivity‐related markers in large cell neuroendocrine carcinoma of the lung
Authors: Ohtaki Yoichi , Kaira Kyoichi , Yajima Toshiki , Erkhem‐Ochir Bilguun , Kawashima Osamu , Kamiyoshihara Mitsuhiro , Igai Hitoshi , Onozato Ryoichi , Ibe Takashi , Kosaka Takayuki , Nakazawa Seshiru , Nagashima Toshiteru , Oyama Tetsunari , Shirabe Ken 
Published: August 2021

AbstractObjectivesVarious drug‐sensitivity markers have been reported to be associated with tumor progression and chemotherapy resistance. Detailed expression profiles of sensitivity markers for cytotoxic chemotherapy in pulmonary large cell neuroendocrine carcinoma (LCNEC) remain unclear. Herein, we aimed to clarify the correlation between the expression of drug‐sensitivity markers and clinicopathological features, prognostic impact, and status of tumor immunity in patients with LCNEC.MethodsWe retrospectively analyzed the correlation between clinicopathological features and the expression of drug‐sensitivity‐related markers, including vascular endothelial growth factor 2 (VEGFR2), thymidylate synthase (TS), tubulin beta 3 class III (TUBB3), topoisomerase I (Topo‐I), and Topo‐II in 92 surgically resected LCNEC samples. Furthermore, we examined the prognostic significance of expression of these and their correlation with the immune cell status.ResultsOverall, high expression of TS, TUBB3, VEGFR2, Topo‐I, and Topo‐II was detected in 50 (54%), 31 (34%), 23 (25%), 65 (71%), and 36 (39%) samples, respectively. Univariate and multivariate analyses revealed that advanced pathological T and N factors, positive lymphatic permeation, and Topo‐II expression were independent unfavorable prognosticators for recurrence‐free survival, and advanced pathological T and N factors, Topo‐II positive expression, and TS positive expression were independent unfavorable prognosticators for overall survival. In terms of correlation with immune cell status, higher expression of VEGFR2 was closely linked to negative PD‐L1 expression.ConclusionsThese findings suggest that elevated Topo‐II and TS expression may contribute to poor outcomes through protumoral biology in patients with LCNEC, and elevated VEGFR2 expression might negatively impact tumor immune reactions in LCNEC.
Screening approaches for identifying fetal alcohol spectrum disorder in children, adolescents, and adults: A systematic review
Authors: Grubb Melissa , Golden Ariella , Withers Abigail , Vellone Daniella , Young Arlene , McLachlan Kaitlyn 
Published: August 2021

AbstractBackgroundFetal alcohol spectrum disorder (FASD) is a prevalent neurodevelopmental disorder that is caused by prenatal alcohol exposure (PAE) and associated with a range of cognitive, affective, and health concerns. Although the identification of FASD can facilitate the provision of interventions and support, and plays a protective role against adverse outcomes, there are high rates of missed detection. The identification of FASD via screening may improve its recognition across settings. The current systematic review examined the available evidence on FASD screening tools and approaches across age groups and settings.MethodsA systematic search was carried out for both peer‐reviewed studies and gray literature sources published between January 1990 and May 2020 and was preregistered with PROSPERO (#CRD42019122077). Studies included in the review focused on human applications of FASD screening in children, adolescents, and adults. The quality of the studies was assessed using the QUADAS‐2 and GRADE frameworks.ResultsThe search yielded 20 screening tools and approaches across 45 studies, broadly characterized in 2 groups. The first group included approaches currently in use that aim to identify individuals at risk of FASD using a range of markers (n = 19) or associated sentinel dysmorphic facial features (n = 6). Another group of studies, characterized as emerging, focused on identifying promising biomarkers of PAE/FASD (n = 20). Overall, we identified limited research supporting the psychometric properties of most screening approaches. The quality review provided evidence of bias due to the common use of case–control designs and lack of adequate reference standards.ConclusionsAlthough several FASD screening tools and approaches are available for use across a range of age groups and settings, the overall evidence base supporting their psychometric properties is weak, with most studies demonstrating significant risk of bias. Service providers should exercise caution in selecting and implementing FASD screening tools given these limitations. It is critically important to accurately identify individuals with FASD across ages and settings to support healthy outcomes. Thus, there is a pressing need for additional research in this area, particularly validation studies in large and representative samples using robust methodological approaches.
Persistence of cerebellar ataxia during chronic ethanol exposure is associated with epigenetic up‐regulation ofFmr1gene expression in rat cerebellum
Authors: Dulman Russell S. , Auta James , Wandling Gabriela M. , Patwell Ryan , Zhang Huaibo , Pandey Subhash C. 
Published: August 2021

AbstractBackgroundAlcohol intoxication produces ataxia by affecting the cerebellum, which coordinates movements. Fragile X mental retardation (FMR) protein is a complex regulator of RNA and synaptic plasticity implicated in fragile X‐associated tremor/ataxia syndrome, which features ataxia and increasedFmr1 mRNA expression resulting from epigenetic dysregulation of FMRP. We recently demonstrated that acute ethanol‐induced ataxia is associated with increased cerebellarFmr1 gene expression via histone modifications in rats, but it is unknown whether similar behavioral and molecular changes occur following chronic ethanol exposure. Here, we investigated the effects of chronic ethanol exposure on ataxia and epigenetically regulated changes inFmr1expression in the cerebellum.MethodsMale adult Sprague‐Dawley rats were trained on the accelerating rotarod and then fed with chronic ethanol or a control Lieber–DeCarli diet while undergoing periodic behavioral testing for ataxia during ethanol exposure and withdrawal. Cerebellar tissues were analyzed for expression of theFmr1 gene and its targets using a real‐time quantitative polymerase chain reaction assay. The epigenetic regulation ofFmr1 was also investigated using a chromatin immunoprecipitation assay.ResultsAtaxic behavior measured by the accelerating rotarod behavioral test developed during chronic ethanol treatment and persisted at both the 8‐h and 24‐h withdrawal time points compared to control diet‐fed rats. In addition, chronic ethanol treatment resulted in up‐regulated expression ofFmr1 mRNA and increased activating epigenetic marks H3K27 acetylation and H3K4 trimethylation at 2 sites within theFmr1promoter. Finally, measurement of the expression of relevant FMRP mRNA targets in the cerebellum showed that chronic ethanol up‐regulated cAMP response element binding (CREB)Creb1,Psd95,Grm5, andGrin2bmRNA expression without alteringGrin2a,Eaa1,or histone acetyltransferases CREB binding protein (Cbp) orp300 mRNA transcripts.ConclusionsThese results suggest that epigenetic regulation ofFmr1and subsequent FMRP regulation of target mRNA transcripts constitute neuroadaptations in the cerebellum that may underlie the persistence of ataxic behavior during chronic ethanol exposure and withdrawal.
Measuring the impact of climate change on agriculture in Vietnam: A panel Ricardian analysis
Authors: Nguyen Chau Trinh , Scrimgeour Frank 
Published: August 2021

AbstractThis article investigates the economic impacts of changes in climatic conditions on Vietnamese agriculture. We apply the two‐step Hsiao method to a 10‐year panel of household data which focuses on the production of 20 crops across seven regions in Vietnam. This study allows for variable market feedbacks across regions that grow different selections of crops. In this way, our article differs from most panel Ricardian analyses which assume uniform market shocks on households. Our analysis also includes climate interactions to allow the effects of temperatures to be dependent on the levels of rainfall. Panel evidence from the Ricardian model suggests heterogeneous climate impacts across seasons and regions. Rising seasonal temperatures are associated with losses to most regions, with spring temperatures being the exception. Increases in summer precipitation are valuable to mitigate the negative effects of rising temperatures. Changes in climate normal should not be the focus of policymakers since the simulation indicates marginal losses to agricultural productivity, both in the short term and the long term. Regions with cool climates are likely to be most affected by the projected climate change.
In vitro data suggest that Indian delta variant B.1.617 of SARS‐CoV‐2 escapes neutralization by both receptor affinity and immune evasion
Authors: Augusto Gilles , Mohsen Mona O. , Zinkhan Simon , Liu Xuelan , Vogel Monique , Bachmann Martin F. 
Published: August 2021

AbstractBackgroundEmerged mutations can be attributed to increased transmissibility of the B.1.617 and B.1.36 Indian delta variants of SARS‐CoV‐2, most notably substitutions L452R/E484Q and N440K, respectively, which occur in the receptor‐binding domain (RBD) of the Spike (S) fusion glycoprotein.ObjectiveWe aimed to assess the effects of mutations L452R/E484Q and N440K (as well as the previously studied mutation E484K present in variants B.1.351 and P.1) on the affinity of RBD for ACE2, SARS‐CoV‐2 main receptor. We also aimed to assess the ability of antibodies induced by natural infection or by immunization with BNT162b2 mRNA vaccine to recognize the mutated versions of the RBD, as well as blocking the interaction RBD‐ACE2, an important surrogate readout for virus neutralization.MethodsTo this end, we produced recombinant wild‐type RBD, as well as RBD containing each of the mutations L452R/E484Q, N440K, or E484K (the latest present in variants of concern B.1.351 and P.1), as well as the ectodomain of ACE2. Using Biolayer Interferometry (BLI), we measured the binding affinity of RBD for ACE2 and the ability of sera from COVID‐19 convalescent donors or subjects immunized with BNT162b2 mRNA vaccine to block this interaction. Finally, we correlated these results with total anti‐RBD IgG titers measured from the same sera by direct ELISA.ResultsThe binding assays showed L452R/E484Q double‐mutant RBD to interact with ACE2 with higher affinity (KD = 4.6 nM) than wild‐type (KD = 21.3 nM) or single mutants N440K (KD = 9.9 nM) and E484K (KD = 19.7 nM) RBDs. Meanwhile, the anti‐RBD IgG titration resulted in lower recognition of mutants E484K and L452R/E484Q by infection‐induced antibodies, whereas only mutant E484K was recognized less by antibodies induced by vaccination. More interestingly, sera from convalescent as well as immunized subjects showed reduced ability to block the interaction between ACE2 and RBD mutants E484K and L452R/E484Q, as shown by the inhibition assays.ConclusionOur data suggest that the newly emerged SARS‐CoV‐2 variant B.1.617, as well as the better‐studied variants B.1.351 and P.1 (all containing a mutation at position E484) display increased transmissibility both due to their higher affinity for the cell receptor ACE2 and their ability to partially bypass immunity generated against the wild‐type virus. For variant B.1.36 (with a point mutation at position N440), only increased affinity seems to play a role.