bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of SARS‐CoV‐2 (COVID‐19) pandemic on patients with lysosomal storage disorders and restoration of services: experience from a specialist centre
Authors: Ramaswami Uma , D'Amore Simona , Finnegan Niamh , Hughes Derralynn , Kazemi Masoud ,   Lysosomal Disorders Team, Royal Free London NHS Foundation Trust
Published: September 2021

AbstractThis study aims to evaluate the impact of the COVID‐19 pandemic on the lysosomal disorders unit (LSDU) at Royal Free London NHS Foundation Trust (RFL), a highly specialised national service for diagnosis and management of adults with lysosomal storage disorders (LSD). Review of home care enzyme replacement therapy (ERT) and emergency care, and COVID‐19 shielding categories as per UK government guidance. New clinical pathways were developed to manage patients safely during the pandemic; staff well‐being initiatives are described. LSDU staff were redeployed and/or had additional roles to support increased needs of hospitalised COVID‐19 patients. During the first lockdown in March 2020, 286 of 602 LSD patients were shielding; 72 of 221 had home care ERT infusions interrupted up to 12 weeks. During the pandemic, there was a 3% reduction in home care nursing support required, with patients learning to self‐cannulate or require support for cannulation only. There were no increased adverse clinical events during this period. Twenty‐one contracted COVID‐19 infection, with one hospitalised and no COVID‐19 related deaths. In 2020, virtual clinics were increased by 88% (video and/or telephone) compared to 2019. RFL well‐being initiatives supported all staff. We provide an overview of the impact of the COVID‐19 pandemic on staff and patients attending a highly specialised rare disease service. As far as we are aware, this is the first detailed narrative on the challenges and subsequent rapid adaptations made, both as part of a large organisation and as a specialist centre. Lessons learnt could be translated to other rare disease services and ensure readiness for any future pandemic.
Smoking‐aggravated oral candidiasis: Nrf2 pathway dampens NLRP3 inflammasome
Authors: Osman Marwan , Papon Nicolas 
Published: September 2021

AbstractWhile cigarette smoke compounds are known to have immunosuppressive effects on the oral mucosa, the relationship between in vivo immune dysfunction caused by smoking and the development of oral Candida infections remains largely unexplored. In a recent issue of The Journal of Cellular and Molecular Medicine, Ye and colleagues provide evidence that smoking increases oral mucosa susceptibility to Candida albicans infection via the activation of the Nrf2 pathway, which in turn negatively regulates the NLRP3 inflammasome. This opens new perspective in considering Nrf2 as a relevant target for smoking‐induced C. albicans‐related oral diseases.
Appropriate care for the elderly in the ICU
Authors: Vincent Jean‐Louis , Creteur Jacques 
Published: September 2021

AbstractLife expectancy is rising worldwide and increasing numbers of elderly patients are being admitted to the intensive care unit (ICU). Because ageing is associated with changes in organ function, increased frailty, reduced activities of daily living, reduced mobility, and reduced cognition, elderly patients represent a particular subgroup of ICU patients. Ethical decisions related to the appropriateness of intensive care and/or life‐sustaining interventions, the withdrawing and withholding of life support, and terminal sedation are more frequent in these patients and will be discussed in this review. Such decisions must be tailored to the individual to take into consideration personal beliefs and wishes.
Mindful of personality trait change: Are treatment effects on personality trait change ephemeral and attributable to changes in states?
Authors: Stieger Mirjam , Allemand Mathias , Roberts Brent W. , Davis Jordan P. 
Published: September 2021

AbstractObjectiveAre treatment effects on personality trait change ephemeral and attributable to change in clinical states? Data of an intervention study were used to examine if change in clinical states (e.g., stress or depression) accounts for change in personality traits and to test whether both changes in traits and clinical states were independently associated with substance use.MethodSeventy‐nine substance use patients (Mage = 25.3, SD = 2.7; 35% female) took part at a 4‐week intervention and completed a total of 15 bi‐monthly assessments across 28 weeks to measure change in traits and states during and after treatment.ResultsThe results suggest that participants showed large trait and state changes over time, which happened rapidly with the majority occurring during the first four weeks. Trait and state changes were highly correlated, but not perfectly redundant. Significant variance in personality trait change remained after controlling for change in clinical states. Moreover, both trait and state change independently predicted substance use.ConclusionPersonality trait change occurred relatively fast and was maintained until the last follow‐up assessment six months after the end of the intervention. Also, the findings point to the notion that the conceptual distinction between traits and states may not be as important as originally thought.
Fetal malnutrition is associated with impairment of endogenous melatonin synthesis in pineal via hypermethylation of promoters of protein kinase C alpha and cAMP response element‐binding
Authors: Han Tianshu , Jiang Wenbo , Wu Huanyu , Wei Wei , Lu Jiang , Lu Huimin , Xu Jiaxu , Gu Wenbo , Guo Xiaoyu , Wang Yu , Ruan Jingqi , Li Yunong , Wang Yuxin , Jiang Xitao , Zhao Shengnan , Li Ying , Sun Changhao 
Published: September 2021

AbstractThis study investigated whether and how fetal malnutrition would influence endogenous melatonin synthesis, and whether such effect of fetal malnutrition would transmit to the next generation. We enrolled 2466 participants and 1313 of their offspring. The urine 6‐hydroxymelatonin sulfate and serum melatonin rhythm were measured. Methylation microarray detection and bioinformatics analysis were performed to identify hub methylated sites. Additionally, rat experiment was performed to elucidate mechanisms. The participants with fetal malnutrition had lower 6‐hydroxymelatonin sulfate (16.59 ± 10.12 μg/24 hours vs 24.29 ± 11.99 μg/24 hours, P < .001) and arear under curve of melatonin rhythm (67.11 ± 8.16 pg/mL vs 77.11 ± 8.04 pg/mL, P < .001). We identified 961 differentially methylated sites, in which the hub methylated sites were locating on protein kinase C alpha (PRKCA) and cAMP response element‐binding protein (CREB1) promoters, mediating the association of fetal malnutrition with impaired melatonin secretion. However, such effects were not observed in the offspring (all P > .05). Impaired histomorphology of pineal, decreased melatonin in serum, pineal, and pinealocyte were also found in the in vivo and in vitro experiments (P < .05 for the differences of the indicators). Hypermethylation of 10 CpG sites on the PRKCA promoter and 8 CpG sites on the CREB1 promoter were identified (all P < .05), which down‐regulated PRKCA and CREB1 expressions, leading to decreased expression of AANAT, and then resulting in the impaired melatonin synthesis. Collectively, fetal malnutrition can impair melatonin synthesis through hypermethylation of PRKCA and CREB1 promoters, and such effects cannot be transmitted to the next generation.
Melatonin reduces proliferation and promotes apoptosis of bladder cancer cells by suppressing O‐GlcNAcylation of cyclin‐dependent‐like kinase 5
Authors: Wu Jinpeng , Tan Zengqi , Li Hongjiao , Lin Meixuan , Jiang Yazhuo , Liang Liang , Ma Qilong , Gou Junjie , Ning Lulu , Li Xiang , Guan Feng 
Published: September 2021

AbstractMelatonin helps to maintain circadian rhythm, exerts anticancer activity, and plays key roles in regulation of glucose homeostasis and energy metabolism. Glycosylation, a form of metabolic flux from glucose or other monosaccharides, is a common post‐translational modification. Dysregulated glycosylation, particularly O‐GlcNAcylation, is often a biomarker of cancer cells. In this study, elevated O‐GlcNAc level in bladder cancer was inhibited by melatonin treatment. Melatonin treatment inhibited proliferation and migration and enhanced apoptosis of bladder cancer cells. Proteomic analysis revealed reduction in cyclin‐dependent‐like kinase 5 (CDK5) expression by melatonin. O‐GlcNAc modification determined the conformation of critical T‐loop domain on CDK5 and further influenced the CDK5 stability. The mechanism whereby melatonin suppressed O‐GlcNAc level was based on decreased glucose uptake and metabolic flux from glucose to UDP‐GlcNAc, and consequent reduction in CDK5 expression. Melatonin treatment, inhibition of O‐GlcNAcylation by OSMI‐1, or mutation of key O‐GlcNAc site strongly suppressed in vivo tumor growth. Our findings indicate that melatonin reduces proliferation and promotes apoptosis of bladder cancer cells by suppressing O‐GlcNAcylation of CDK5.
Interdental and subgingival microbiota may affect the tongue microbial ecology and oral malodour in health, gingivitis and periodontitis
Authors: Stephen Abish S. , Dhadwal Narinder , Nagala Vamshidhar , Gonzales‐Marin Cecilia , Gillam David G. , Bradshaw David J. , Burnett Gary R. , Allaker Robert P. 
Published: September 2021

AbstractBackground and ObjectiveOral malodour is often observed in gingivitis and chronic periodontitis patients, and the tongue microbiota is thought to play a major role in malodorous gas production, including volatile sulphur compounds (VSCs) such as hydrogen sulphide (H2S) and methanethiol (CH3SH). This study aimed to examine the link between the presence of VSCs in mouth air (as a marker of oral malodour) and the oral bacterial ecology in the tongue and periodontal niches of healthy, gingivitis and periodontitis patients.MethodsParticipants were clinically assessed using plaque index, bleeding on probing (BOP) and periodontal probing depths, and VSC concentrations in their oral cavity measured using a portable gas chromatograph. Tongue scrapings, subgingival and interdental plaque were collected from healthy individuals (n = 22), and those with gingivitis (n = 14) or chronic periodontitis (n = 15). The bacterial 16S rRNA gene region V3‐V4 in these samples was sequenced, and the sequences were analysed using the minimum entropy decomposition pipeline.ResultsElevated VSC concentrations and CH3SH:H2S were observed in periodontitis compared with health. Significant ecological differences were observed in the tongue microbiota of healthy subjects with high plaque scores compared to low plaque scores, suggesting a possible connection between the microbiota of the tongue and the periodontium and that key dysbiotic changes may be initiated in the clinically healthy individuals who have higher dental plaque accumulation. Greater subgingival bacterial diversity was positively associated with H2S in mouth air. Periodontopathic bacteria known to be prolific VSC producers increased in abundance on the tongue associated with increased bleeding on probing (BOP) and total percentage of periodontal pockets >6 mm, supporting the suggestion that the tongue may become a reservoir for periodontopathogens.ConclusionThis study highlights the importance of the periodontal microbiota in malodour and has detected dysbiotic changes in the tongue microbiota in periodontitis.
Life‐history traits of Guntea loach, Lepidocephalichthys guntea (Hamilton, 1822) in the Payra River, southern Bangladesh
Authors: Saha Newton , Roy Prosun , Nadia Zubyda Mushtari , Islam SM Majharul , Hossain Md. Yeamin 
Published: September 2021

AbstractThe present study provides the first wide‐ranging elucidation of life‐history traits, including length–frequency distribution (LFD), length–weight and length–length relationship (LWR and LLR), form factor (a3.0), best condition factor (allometric, KA; Fulton, KF; relative, KR; and relative weight, WR), length at first maturity (Lm), natural mortality (Mw) and optimum catchable length (Lopt) of Lepidocephalichthyes guntea from the Payra River in southern Bangladesh. A total of 470 fishes were randomly collected seasonally from February 2019 to January 2020, using several traditional fishing gears (cast nets; drag nets; lift nets; and gill nets). The total length (TL), standard length (SL) and total body weight (BW) of each individual fish were measured with a 0.01 cm and 0.01 g precision, respectively. The TL size classes of 6.00–6.99 cm and 7.00–7.99 cm TL were the numerically dominant groups among the total fish population. Exponential b values of LWR (TL vs. BW) indicate a positive allometric growth (b = 3.20) pattern in the Payra River. The b value of LLR also indicates the same growth pattern. The estimated a3.0 value was 0.007, indicating the fish has an elongated body profile. Among the four types of condition factors, KF is the best‐suited tool for evaluating the well‐being of L. guntea in the Payra River. Additionally, WR exhibited very significant divergence from 100 (p < .0001), designating an imbalanced habitat for L. guntea. The calculated Lm, Mw and Lopt values were 6.54 (~6.5 cm) in TL, 1.16/year and 7.46 cm TL for L. guntea in the Payra River, respectively. Thus, the results of the present study could be used in the future for improved management of this species in Payra River, as well as for linking ecosystems.
CRISPR/SpCas9‐mediated double knockout of barley Microrchidia MORC1 and MORC6a reveals their strong involvement in plant immunity, transcriptional gene silencing and plant growth
Authors: Galli Matteo , Martiny Engie , Imani Jafargholi , Kumar Neelendra , Koch Aline , Steinbrenner Jens , Kogel Karl‐Heinz 
Published: September 2021

SummaryThe Microrchidia (MORC) family proteins are important nuclear regulators in both animals and plants with critical roles in epigenetic gene silencing and genome stabilization. In the crop plant barley (Hordeum vulgare), seven MORC gene family members have been described. While barley HvMORC1 has been functionally characterized, very little information is available about other HvMORC paralogs. In this study, we elucidate the role of HvMORC6a and its potential interactors in regulating plant immunity via analysis of CRISPR/SpCas9‐mediated single and double knockout (dKO) mutants, hvmorc1 (previously generated and characterized by our group), hvmorc6a, and hvmorc1/6a. For generation of hvmorc1/6a, we utilized two different strategies: (i) successive Agrobacterium‐mediated transformation of homozygous single mutants, hvmorc1 and hvmorc6a, with the respective second construct, and (ii) simultaneous transformation with both hvmorc1 and hvmorc6a CRISPR/SpCas9 constructs. Total mutation efficiency in transformed homozygous single mutants ranged from 80 to 90%, while upon simultaneous transformation, SpCas9‐induced mutation in both HvMORC1 and HvMORC6a genes was observed in 58% of T0 plants. Subsequent infection assays showed that HvMORC6a covers a key role in resistance to biotrophic (Blumeria graminis) and necrotrophic (Fusarium graminearum) plant pathogenic fungi, where the dKO hvmorc1/6a showed the strongest resistant phenotype. Consistent with this, the dKO showed highest levels of basal PR gene expression and derepression of TEs. Finally, we demonstrate that HvMORC1 and HvMORC6a form distinct nucleocytoplasmic homo‐/heteromers with other HvMORCs and interact with components of the RNA‐directed DNA methylation (RdDM) pathway, further substantiating that MORC proteins are involved in the regulation of TEs in barley.
A small heat shock protein, GmHSP17.9, from nodule confers symbiotic nitrogen fixation and seed yield in soybean
Authors: Yang Zhanwu , Du Hui , Xing Xinzhu , Li Wenlong , Kong Youbin , Li Xihuan , Zhang Caiying 
Published: September 2021

SummaryLegume–rhizobia symbiosis enables biological nitrogen fixation to improve crop production for sustainable agriculture. Small heat shock proteins (sHSPs) are involved in multiple environmental stresses and plant development processes. However, the role of sHSPs in nodule development in soybean remains largely unknown. In the present study, we identified a nodule‐localized sHSP, called GmHSP17.9, in soybean, which was markedly up‐regulated during nodule development. GmHSP17.9 was specifically expressed in the infected regions of the nodules. GmHSP17.9 overexpression and RNAi in transgenic composite plants and loss of function in CRISPR‐Cas9 gene‐editing mutant plants in soybean resulted in remarkable alterations in nodule number, nodule fresh weight, nitrogenase activity, contents of poly β‐hydroxybutyrate bodies (PHBs), ureide and total nitrogen content, which caused significant changes in plant growth and seed yield. GmHSP17.9 was also found to act as a chaperone for its interacting partner, GmNOD100, a sucrose synthase in soybean nodules which was also preferentially expressed in the infected zone of nodules, similar to GmHSP17.9. Functional analysis of GmNOD100 in composite transgenic plants revealed that GmNOD100 played an essential role in soybean nodulation. The hsp17.9 lines showed markedly more reduced sucrose synthase activity, lower contents of UDP‐glucose and acetyl coenzyme A (acetyl‐CoA), and decreased activity of succinic dehydrogenase (SDH) in the tricarboxylic acid (TCA) cycle in nodules due to the missing interaction with GmNOD100. Our findings reveal an important role and an unprecedented molecular mechanism of sHSPs in nodule development and nitrogen fixation in soybean.
The Importance of Risk Management: What is Missing in ISO Standards?
Authors: Björnsdóttir Svana Helen , Jensson Páll , de Boer Robert J. , Thorsteinsson Saemundur E. 
Published: September 2021

AbstractThe overall aim of this article is to contribute to the further development of the area of risk analysis and risk management in the International Organization for for Standardization (ISO) standards by strengthening its scientific basis. Industrial standards, especially ISO standards, are the tools organizations use to manage their risk, through following their guidance and complying with their requirements. Organizations confirm their compliance with these standards through certification, which means that they heavily depend upon the quality of the ISO standards to enable them to effectively manage their risk. The purpose of this study is to investigate what guidance is given on key elements of risk management and how well ISO standards are aligned with state‐of‐the‐art risk management literature. Eighteen ISO standards, all addressing risk management, were reviewed in this study with regard to risk terminology and guidance. The results of the study confirm the increasing importance of risk management for business. However, the study also shows a lack of guidance on doing risk analysis in the industrial standards examined. The ISO management system standards and guidelines are not aligned with the scientific literature on risk and are not appropriate for the management of risk arising from complex interactions and emergent behavior that is inherent in present‐day sociotechnical systems.
Korean Specificational Pseudoclefts as Caseless Focus Nominal Extraction*
Authors: Park Dongwoo 
Published: September 2021

AbstractKorean specificational pseudoclefts exhibit a paradox. On the one hand, anaphor binding facts indicate that the pivot (or an element co‐indexed with it) must originate in a position located within the presupposition CP. Nonetheless, specificational pseudoclefts appear to be island‐insensitive. To resolve this paradox, I propose an extraction analysis whereby only caseless focus nominals base‐generated in the complement position of verbs or in the left‐periphery of the presupposition CP may function as pivots, and reach their surface position. This proposal has several implications. First, caseless nominals are structurally reduced, when compared to case‐marked nominals containing a case projection. Second, caseless nominals base‐generated in the left‐periphery of CPs can be foci conveying contrastive (exhaustive) new information. Third, anaphor connectivity effects are tied to syntactic movement of focus phrases and reconstruction. Lastly, specificational pseudoclefts and copular constructions do not have the same underlying structure.
Comparison of serum versus EDTA plasma in canine major crossmatch reactions
Authors: Caudill Megan N. , Meichner Kristina , Koenig Amie , Berghaus Roy D. , Garner Bridget 
Published: September 2021

AbstractBackgroundProtocols for crossmatch reactions vary in veterinary medicine, particularly regarding the use of recipient serum vs plasma. Sources suggest that major crossmatch results might differ when recipient plasma is used instead of serum, but there are conflicting reports as to the exact effects on the results.ObjectivesThe aim of this study was to determine the frequency and degree of discrepancy, if any, between canine major crossmatch reactions using serum versus EDTA plasma, performed via a standard tube method.MethodsOne hundred duplicate canine major crossmatch reactions were performed with both serum and EDTA plasma from 100 different “recipient” dogs against erythrocytes from a single, healthy “donor.” Decreasing concentrations of a rabbit anti‐dog erythrocyte antibody were added to generate strong positive, weak positive, and negative results for each crossmatch reaction. Crossmatch results were followed through the following phases: immediate spin, cold, warm, albumin, and Coombs. Semi‐quantitative results were compared between reactions using serum vs EDTA plasma.ResultsWeak positive, major crossmatch reactions were significantly more likely to demonstrate stronger agglutination in EDTA plasma compared with serum in the immediate spin phase, cold phase, warm phase, and albumin phase (P < 0.001). There was no statistically significant difference between serum and EDTA plasma results in the Coombs’ phase (P = 0.313).ConclusionsIn this experimental setting, EDTA plasma and serum were both deemed acceptable for use in canine major crossmatch reactions. EDTA plasma might be preferable to detect weak agglutination with more sensitivity and reduce recipient blood volumes needed to complete the crossmatch reaction.
Topical bevacizumab for the treatment of corneal vascularization in dogs: A case series
Authors: Muellerleile Lisa‐Marie , Bernkopf Michael , Wambacher Michael , Nell Barbara 
Published: September 2021

AbstractObjectiveTo evaluate the effect and safety of topical anti‐human vascular endothelial growth factor bevacizumab in dogs with persistent corneal vascularization.Animals studiedProspective case series of 15 adult dogs (20 eyes).ProceduresDogs received 0.25% bevacizumab eye drops BID for 28 days. Follow‐ups were scheduled 28 days and 6–7 months after treatment start. Macroscopic findings were scored for conjunctival hyperemia, chemosis, ocular discharge, corneal edema, vascularization, and pigmentation. Vascularized area was assessed by analyzing photographs using an imaging software.ResultsThe treatment response was variable. Some cases showed a marked reduction in vascularized area and edema, while other eyes had subtle signs of improvement. Vascularization score decreased from 1.5 to 1.1 and vascularized area was reduced by 48.8% after 28 days. A thinning of vessels, consolidation of areal bleedings into fine vascular networks, decrease in distal vessel branching, and a change from blurry vascularized beds into demarcated thin vessels were observed. One dog developed a SCCED 6 months after the last bevacizumab administration. Two dogs died 4 and 4.5 months after the last bevacizumab administration, aged 16 and 12 years, respectively. In all events, a causal relationship is unlikely but cannot be ruled out with certainty.ConclusionsOur findings suggest that topical 0.25% bevacizumab may be an effective treatment option for corneal vascularization in dogs. Further long‐term placebo‐controlled studies with larger patient cohorts are recommended to provide scientific evidence of efficacy and to investigate dosage, safety, possible use as a single treatment, and routes of administration.