bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leveraging genetics to improve Body Mass Index increase prediction in the first-episode of psychosis
Authors: Muntané Gerard , Vázquez-Bourgon Javier , Sada Ester , Martorell Lourdes , Papiol Sergi , Bosch Elena , Navarro Arcadi , Crespo-Facorro Benedicto , Vilella Elisabet 
Published: February 2022

AbstractBackgroundIndividuals with a first episode of psychosis (FEP) show rapid weight gain during the first months of treatment, which is associated with reduction in psychiatric and physical health. Although genetics is assumed to be a significant contributor to this weight gain, its exact role is unknown.MethodsReference GWAS from BMI and SCZ were obtained to evaluate the pleiotropic landscape between both traits using the pleioFDR software. In parallel, we gathered a population-based FEP cohort of 381 individuals and BMI Polygenic risk-scores (PRS) were evaluated on a sample of 224 individuals. Subsequently, the PRSs obtained from both BMI and the variants shared between the two traits were incorporated into risk models that included demographic and clinical variable to predict BMI increase (ΔBMI) on an independent sample of 157 patients.ResultsBMI PRS significantly improved the prediction of absolute BMI and ΔBMI during the first 12 months after the onset of psychotic symptoms. This improvement, was mainly explained by shared variants between SCZ and BMI. In contrast, absolute BMI was predicted mainly by non-shared variants.ConclusionsWe validated, for the first time, that genetic factors play a key in the determination of both BMI and ΔBMI in FEP. This finding has important clinical implications in identifying individuals who require specific treatment strategies. Improved risk classification may help prevent associated adverse metabolic events, and reduce overtreatment and costs for both individuals and the healthcare system. It also highlights the importance of studying genetic pleiotropy in the context of medically important comorbidities.
BK channel properties correlate with neurobehavioral severity in three KCNMA1-linked channelopathy mouse models
Authors: Park Su Mi , Roache Cooper E. , Iffland Philip H. , Moldenhauer Hans J. , Matychak Katia K. , Plante Amber E. , Lieberman Abby G. , Crino Peter B. , Meredith Andrea L. 
Published: February 2022

ABSTRACTKCNMA1 forms the pore of BK K+ channels, which regulate neuronal and muscle excitability. Recently, genetic screening identified heterozygous KCNMA1 variants in a subset of patients with debilitating paroxysmal non-kinesigenic dyskinesia, presenting with or without epilepsy (PNKD3). However, the relevance of KCNMA1 mutations and the basis for clinical heterogeneity in PNKD3 has not been established. Here we evaluate the relative severity of three KCNMA1 patient variants in BK channels, neurons, and mice. In heterologous cells, BKN999S and BKD434G channels displayed gain-of-function (GOF) properties, whereas BKH444Q channels showed loss-of-function (LOF) properties. The relative degree of channel activity was BKN999S > BKD434G > WT > BKH444Q. BK currents and action potential firing were increased, and seizure thresholds decreased, in Kcnma1N999S/WT and Kcnma1D434G/WT transgenic mice but not Kcnma1H444Q/WT mice. In a novel behavioral test for paroxysmal dyskinesia, the more severely affected Kcnma1N999S/WT mice became immobile after stress, consistent with stress-induced immobility episodes observed in PNKD3-affected individuals. Homozygous Kcnma1D434G/D434G mice showed similar immobility, but in contrast, homozygous Kcnma1H444Q/H444Q mice displayed hyperkinetic behavior. These data establish the relative pathogenic potential of patient alleles as N999S > D434G > H444Q and validate Kcnma1N999S/WT mice as a model for PNKD3 with increased seizure propensity.
Osteocalcin binds to a GPRC6A Venus fly trap allosteric site to positively modulate GPRC6A signaling
Authors: Agarwal Rupesh , Pi Min , Ye Ruisong , Smith Micholas Dean , Smith Jeremy C. , Quarles L. Darryl 
Published: February 2022

AbstractGPRC6A is a member of the Family C G-protein coupled receptors that is activated by cations, L-amino acids, the osteocalcin (Ocn) peptide, and testosterone. GPRC6A functions as a master regulator of energy metabolism and sex hormone production. Based on homology to the related receptors mGluR5 and CaSR, GPRC6A’s multiple ligand specificity is likely based on an orthosteric ligand binding site in the bilobed Venus fly trap (VFT) domain together with two positive allosteric modulator (PAM) sites, one in the VFT and the other in the 7TM domain. Here, we show that Ocn acts as a PAM for GPRC6A by binding to a site in the VFT that is distinct from the orthosteric site for calcium and L-amino acids. In agreement with this finding, alternatively spliced GPRC6A isoforms 2 and 3, which lack regions of the VFT, and mutations in the predicted Ocn binding site, K352E and H355P, prevent Ocn activation of GPRC6A. These observations provide a structural framework for understanding the ability of multiple distinct classes of compounds to activate GPRC6A and set the stage to develop novel small molecules to activate and inhibit this receptor.
NaCl Triggers the Sessile-to-Motile Transition of Bacillus subtilis
Authors: Murugan Prem Anand , Gupta Manish Kumar , Sankar T. Sabari , Chandran Sivasurender , Matheshwaran Saravanan 
Published: February 2022

AbstractVarious chemical cues are known to alter the motile and sessile states of bacteria differentially and, in turn, the formation of biofilms. However, the underlying mechanisms at the cellular and molecular level remain less understood, which severely limits our ability to control biofilms. Here, we systematically studied the effects of NaCl on the dynamics of biofilm formation across various length scales and the associated changes in the regulation of gene expression in an undomesticated natural isolate of Bacillus subtilis. Interestingly, NaCl induced significant changes in the architecture of pellicles and yielded systematic increase in lateral expansion rates of biofilms when grown on an agar surface. At the microscopic level, both in the presence and absence of NaCl, bacteria displayed super-diffusive motion at times lesser than a second. However, at larger delay times, we observed an intriguing NaCl-induced transition from sub-diffusion behavior of individual bacterial cells to rapid diffusion behavior. In addition, NaCl reduced the dynamical heterogeneity of the bacterial cells within the biofilm. The reduced heterogeneity and the increased flagellation in a subpopulation of cells in the presence of NaCl corroborates well with the observed higher motility of the cells. Further, the cellular uptake of NaCl resulted in the downregulation of several genes underlying the formation of biofilms, revealing the role of chemical cues like NaCl in controlling the gene regulatory circuit underlying the sessile to motile transition. Our study opens a new avenue to decipher the competitive advantage provided to the subcellular populations by NaCl due to lifestyle switch in Bacillus subtilis.
Recombinant production of growth factors for application in cell culture
Authors: Venkatesan Meenakshi , Semper Cameron , DiLeo Rosa , Mesa Nathalie , Stogios Peter J , Savchenko Alexei 
Published: February 2022

SummaryCulturing eukaryotic cells has widespread applications in research and industry, including the emerging field of cell-cultured meat production colloquially referred to as “cellular agriculture”. These applications are often restricted by the high cost of growth medium necessary for cell growth. Mitogenic protein growth factors (GFs) are essential components of growth medium and account for upwards of 90% of the total costs. Here, we present a set of expression constructs and a simplified protocol for recombinant production of functionally active GFs, including FGF-2, IGF-1, PDGF-BB and TGF-β1 in Escherichia coli. Using this expression system, we produced soluble GFs from species including bovine, chicken, and fish. Bioactivity analysis revealed orthologs with improved performance compared to commercially available alternatives. We estimated that the production cost of GFs using our methodology will significantly reduce the cost of cell culture medium, facilitating low-cost protocols tailored for cultured meat production and tissue engineering.
Effect of corporate environmental strategies on firms’ competitiveness, the mediating role of supply chain collaboration
Authors: Owusu Kwateng Kwame , Tetteh Francis Kamewor , Atchulo Hunaisu Ben , Opoku-Mensah Shirley 
Published: February 2022

Purpose
The purpose of this is to test the relationship between corporate environmental strategies (CES) and firms’ competitiveness (FC) through collaboration.

Design/methodology/approach
Selected companies from Ghana Club 100 were used as the sample for this study. This study used regression to test the hypothesized paths.

Findings
The results indicated that a unit change in CES results in a 42.7% alteration in FC – all things being equal. Also, as revealed by the study, supply chain collaboration (SCC) is not a significant predictor of FC. However, SCC plays an indirect role in enhancing the relationship between CES and FC. The results showed that CES act as a significant predictor of a company’s collaboration in its supply chain.

Practical implications
The findings will enlighten firms to outline and implement appropriate environmental strategies to sustain their competitive advantage.

Originality/value
This study is very rare in the African context; hence, it adds to the extant literature by providing a contemporary perspective of CES and FC.
Ipriflavone as a non‐steroidal glucocorticoid receptor antagonist ameliorates diabetic cognitive impairment in mice
Authors: Nie Ruifang , Lu Jian , Xu Rui , Yang Juanzhen , Shen Xingyi , Ouyang Xingnan , Zhu Danyang , Huang Yujie , Zhao Tong , Zhao Xuejian , Lu Yin , Qian Minyi , Wang Jiaying , Shen Xu 
Published: February 2022

AbstractDiabetic cognitive impairment (DCI) is a common diabetic complication with hallmarks of loss of learning ability and disorders of memory and behavior. Glucocorticoid receptor (GR) dysfunction is a main reason for neuronal impairment in brain of diabetic patients. Here, we determined that ipriflavone (IP) a clinical anti‐osteoporosis drug functioned as a non‐steroidal GR antagonist and efficiently ameliorated learning and memory dysfunction in both type 1 and 2 diabetic mice. The underlying mechanism has been intensively investigated by assay against the diabetic mice with GR‐specific knockdown in the brain by injection of adeno‐associated virus (AAV)‐ePHP‐si‐GR. IP suppressed tau hyperphosphorylation through GR/PI3K/AKT/GSK3β pathway, alleviated neuronal inflammation through GR/NF‐κB/NLRP3/ASC/Caspase‐1 pathway, and protected against synaptic impairment through GR/CREB/BDNF pathway. To our knowledge, our work might be the first to expound the detailed mechanism underlying the amelioration of non‐steroidal GR antagonist on DCI‐like pathology in mice and report the potential of IP in treatment of DCI.
The utility of routine screening for anaemia at 36 weeks gestation
Authors: Purcell Samuel , Beckmann Michael 
Published: February 2022

Anaemia is a global disease, affecting over 1 billion people worldwide; 12% of Australian women experience anaemia in pregnancy. Professional bodies/institutions recommend screening for and treating anaemia in pregnancy but there is inconsistency in recommendations for when to screen. A ten‐year retrospective analysis was undertaken of 10 518 pregnancies where there was not a specific indication for repeat blood tests. Using a 28‐week haemoglobin (Hb) threshold of ≥110 g/L, seven out of ten could safely forego a routine 36‐week full blood count. Less than 2.5% would then be anaemic at 36 weeks, none of whom would have had a Hb < 90 g/L.
Has EVAR changed the outcomes of ruptured abdominal aortic aneurysms? A decades worth of experience in an Australian Teaching Hospital
Authors: de Boer Madeleine , Shiraev Timothy , Waller Jacob , Qasabian Raffi 
Published: February 2022

AbstractBackgroundRuptured abdominal aortic aneurysms (rAAA) are associated with significant mortality, and equipoise remains as to whether patients managed with endovascular stent grafts (rEVAR) demonstrate better outcomes when compared to traditional open repair (OR). This study sought to examine the outcomes of patients presenting with rAAA to our institution and assess the perioperative outcomes and outpatient mortality of patients over the past decade.MethodsA retrospective analysis was conducted. Patients treated for rAAA between 2010 and 2019 were identified from a search of the hospital database for ACHI and ICD‐10 codes for repair of AAA. Demographic, operative and post‐operative variables were collected from electronic medical records of identified patients.ResultsEighty patients were identified, 51 of whom presented with a rAAA. The majority of repairs were rEVARs (59%). Median age was 76 years. Median length of admission to ICU was 3 days, and median length of hospital admission was 10 days. Overall in‐patient mortality was 26%, with rates of 39% at 3 years and 47% at 5 years. No significant difference in outpatient mortality was found in patients undergoing rEVAR compared to OR, with rates of 61% at 5 years compared to 65% at 5 years, respectively (p = 0.8).ConclusionPerioperative outcomes of our cohort of patients undergoing endovascular repair compared to open repair for ruptured and symptomatic AAAs are comparable over the past decade. Given equipoise remains between repair methods, further observational studies are required to quantify benefits of OR and endovascular repairs for ruptured and symptomatic AAAs.
Association between ultrasound quality and test performance for HCC surveillance in patients with cirrhosis: a retrospective cohort study
Authors: Chong Nicolas , Schoenberger Haley , Yekkaluri Sruthi , Fetzer David T. , Rich Nicole E. , Yokoo Takeshi , Gopal Purva , Manwaring Carrie , Quirk Lisa , Singal Amit G. 
Published: February 2022

SummaryBackgroundUltrasound visualisation is limited in approximately 20% of patients with cirrhosis undergoing hepatocellular carcinoma (HCC) surveillance; however, it is unknown if impaired visualisation directly impacts test performance. We aimed to evaluate the association between ultrasound visualisation and surveillance test performance.MethodsWe performed a retrospective cohort study among patients with cirrhosis, with or without HCC, who underwent ultrasound‐based surveillance at two large health systems between July 2016 and July 2019. Ultrasound visualisation assessment was recorded by interpreting radiologists using the ultrasound LI‐RADS Visualisation score. We performed logistic regression analyses to evaluate the association between ultrasound visualisation and diagnostic test performance. We assessed sensitivity for HCC detection among ultrasounds performed in the year prior to HCC diagnoses and specificity using ultrasounds in those without HCC.ResultsAmong 186 patients with HCC, severely limited visualisation (Vis Score C) on ultrasound prior to HCC diagnosis was associated with increased odds of false‐negative results, that is lower sensitivity (OR 7.94, 95% CI 1.23‐51.16) in multivariable analysis. Ultrasound sensitivity with visualisation scores A or B exceeded 75%, compared to only 27.3% with visualisation score C. Among 2052 cirrhosis patients without HCC, moderate visualisation limitations (Vis score B) were associated with increased odds of false‐positive results (OR 1.60, 1.13‐2.27), although specificity exceeded 95% across all visualisation scores.ConclusionsImpaired ultrasound visualisation is associated with worse surveillance test performance. Alternative blood‐based biomarkers and imaging strategies are needed for patients at risk for ultrasound‐based surveillance failure.
Investigation of the manufacture development of early Chinese ink in the Western Han dynasty
Authors: Ren Meng , Guan Li , Wang Na , Xu Changqing , Cui Yaping , He Donghong , Wang Changsui , Yang Yimin 
Published: February 2022

AbstractChinese ink, generally produced in a stick form, was often like pellets before the Western Han dynasty (202 bce–8 ce) according to literary records and a few archaeological discoveries. However, their composition and manufacture have not been scientifically analysed to date. In this study, the ink pellets roughly dated to 2000 years ago from two royal tombs of the Han dynasty (the Nanyue King's tomb and the Marquis of Haihun's tomb) were analyzed by micro‐/non‐destructive methods, including synchrotron radiation‐based micro‐computed tomography (SR‐μCT), Fourier‐transform infrared spectroscopy (FTIR) and pyrolysis gas chromatography mass spectrometry (Py‐GC/MS). The results reveal that they were made from pine soot, and the production technology of the later Haihun ink was more complex than that of the earlier Nanyue King ink. The microstructure of the ink pellets indicated that some kind of glue should be used in the Haihun ink, which is the earliest case of glue addition. Moreover, plant extracts, including borneol and cedar oil, were detected in the Haihun ink, reflecting another aspect of progress in ink production history. These technical breakthroughs imply that the Western Han dynasty is a critical period for the development of traditional ink manufacture, and the shape transformation of Chinese ink is closely related to the evolution of ink production technology during this specific period.
Measuring the gig economy in Canada using administrative data
Authors: Jeon Sung‐Hee , Liu Huju , Ostrovsky Yuri 
Published: February 2022

AbstractA rapidly growing literature on informal work increasingly turns to administrative data to document changes in the size of informal economy and to learn more about the characteristics of freelancers, on‐demand/platform workers and similar types of workers commonly referred to as “gig workers.” These studies have established a conceptual link between the work arrangements of gig workers and how these are reported in tax data. We contribute to this literature by introducing a method of identifying gig workers specific to the way work arrangements are reported in the Canadian tax system and estimating the size of the gig economy in Canada using administrative data. Based on our definition, the share of gig workers among all workers rose from 5.5% in 2005 to 8.2% in 2016. Some of this increase coincided with the introduction and proliferation of online platforms. Our analysis highlights gender differences in the trends and characteristics of gig workers. By linking administrative data to 2016 census microdata, we are also able to examine educational and occupational differences in the prevalence of gig workers.
Optimised minus lens overcorrection for paediatric intermittent exotropia: A randomised clinical trial
Authors: Ale Magar Jit B. , Shah Shaheen P. , Webber Ann , Sleep Michael G. , Dai Shuan H. 
Published: February 2022

AbstractBackgroundAim of this study was to evaluate the efficacy of a novel algorithm to customise overminus lens therapy in intermittent exotropia (IXT) based on clinical factors associated with control of the deviation.MethodsClinical parameters in IXT vary among individuals. Based on individual's physiological factors, an algorithm was developed. Children aged between 4 and 15 years with IXT were randomised into OML and observation groups. Participants in the observation group were corrected for any significant refractive error. IXT control score, angle of deviation, refraction, axial length and stereopsis were examined at baseline and follow up ranging between 6 and 15 months and compared. Compliance and tolerance to OML was determined by a symptom survey.ResultsThe OML power ranged between −1.00D and − 6.25D. Of the total 141 participants (mean age 6.8 ± 2.5 year), 77 were in the OML and 66 were in observation group. IXT control score improved (mean difference − 2.5 ± 1.1; p < 0.001) and angle of deviation reduced (6.9 ± 7.2pd; p < 0.001) significantly in the OML group only. Compliance rate to OML wear was 80%; 90% never or rarely experienced asthenopia symptoms. Slightly greater myopic shift (−0.36 ± 0.53D vs. −0.18 ± 0.55D) and change in axial length (0.17 vs. 0.14 mm) were observed in the OML group, but these differences were not statistically significant.ConclusionsA customised OML, calculated using this novel algorithm was effective in improving distance control, angle of deviation and stereopsis. Glasses wear was highly tolerable.
Running a paediatric ambulatory sleep service in a pandemic and beyond
Authors: Johnson Jo‐Anne , Burrows Katrina , Trinidade Aaron 
Published: February 2022

AbstractObjectivesIn response COVID‐19, re‐establishing safe elective services was prioritised in the UK. We assess the impact on face‐to‐face hospital attendance, cost and efficiency of implementing a virtual sleep clinic (intervention 1) to screen for children requiring level 3 ambulatory sleep studies using newly implemented ENT‐UK guidelines for obstructive sleep apnoea (OSA) investigation (intervention 2). Objectives: (1) compare the proportion of children attending sleep clinic undertaking a sleep study before and after implementation of these interventions; (2) compare clinic cancellations and first‐time success rates of sleep studies before and after intervention.DesignRetrospective analysis.SettingDistrict general hospital paediatric sleep clinic.ParticipantsChildren aged 3 months to 16 years referred to sleep clinic by ENT for investigation of OSA over 3 months immediately following interventions (1 June 2020 – 1 September 2020) to the same period in the previous year (1 June 2019 – 1 September 2019).Main outcome measuresNumber of children attending sleep clinic, date of birth/age of children attending sleep clinic, number of children undergoing sleep study, diagnostic outcomes, number of appointment cancellations, number of first‐time sleep study failures.ResultsPost intervention, there was a significant reduction in the proportion of children undertaking ambulatory sleep studies, and nonsignificant reductions in appointment cancellations and in first‐time sleep study failures.ConclusionsThe introduction of the virtual sleep clinic meant that only those children requiring a sleep study attended a face‐to‐face appointment, which led to reduced face‐to‐face attendance. There were also unintended cost‐effectiveness and efficiency benefits, with potential longer‐term learning implications for the wider sleep community and other diagnostic services.
Enhancer RNA: What we know and what we can achieve
Authors: Han Zhenzhen , Li Wei 
Published: February 2022

AbstractEnhancers are important cis‐acting elements that can regulate gene transcription and cell fate alongside promoters. In fact, many human cancers and diseases are associated with the malfunction of enhancers. Recent studies have shown that enhancers can produce enhancer RNAs (eRNAs) by RNA polymerase II. In this review, we discuss eRNA production, characteristics, functions and mechanics. eRNAs can determine chromatin accessibility, histone modification and gene expression by constructing a ‘chromatin loop’, thereby bringing enhancers to their target gene. eRNA can also be involved in the phase separation with enhancers and other proteins. eRNAs are abundant, and importantly, tissue‐specific in tumours, various diseases and stem cells; thus, eRNAs can be a potential target for disease diagnosis and treatment. As eRNA is produced from the active transcription of enhancers and is involved in the regulation of cell fate, its manipulation will influence cell function, and therefore, it can be a new target for biological therapy.