bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alzheimer’s disease associated AKAP9 I2558M mutation alters posttranslational modification and interactome of tau and cellular functions in CRISPR‐edited human neuronal cells
Authors: You Yang , Hersh Samuel W. , Aslebagh Roshanak , Shaffer Scott A. , Ikezu Seiko , Mez Jesse , Lunetta Kathryn L. , Logue Mark W. , Farrer Lindsay A. , Ikezu Tsuneya 
Published: May 2022

AbstractAlzheimer's disease (AD) is a pervasive neurodegeneration disease with high heritability. In this study, we employed CRISPR‐Cas9‐engineered technology to investigate the effects of a rare mutation (rs144662445) in the A kinase anchoring protein 9 (AKAP9) gene, which is associated with AD in African Americans (AA), on tau pathology and the tau interactome in SH‐SY5Y P301L neuron‐like cells. The mutation significantly increased the level of phosphorylated tau, specifically at the site Ser396/Ser404. Moreover, analyses of the tau interactome measured by affinity purification‐mass spectrometry revealed that differentially expressed tau‐interacting proteins in AKAP9 mutant cells were associated with RNA translation, RNA localization and oxidative activity, recapitulating the tau interactome signature previously reported with human AD brain samples. Importantly, these results were further validated by functional studies showing a significant reduction in protein synthesis activity and excessive oxidative stress in AKAP9 mutant compared with wild type cells in a tau‐dependent manner, which are mirrored with pathological phenotype frequently seen in AD. Our results demonstrated specific effects of rs14462445 on mis‐processing of tau and suggest a potential role of AKAP9 in AD pathogenesis.
High‐resolution diffusion tensor imaging identifies hippocampal volume loss without diffusion changes in individuals with prenatal alcohol exposure
Authors: Solar Kevin Grant , Treit Sarah , Beaulieu Christian 
Published: May 2022

AbstractBackgroundMagnetic resonance imaging (MRI) studies of prenatal alcohol exposure (PAE) commonly report reduced hippocampal volumes, which animal models suggest may result from microstructural changes that include cell loss and altered myelination. Diffusion tensor imaging (DTI) is sensitive to microstructural changes but has not yet been used to study the hippocampus in PAE.MethodsThirty‐six healthy controls (19 females; 8 to 24 years) and 19 participants with PAE (8 females; 8 to 23 years) underwent high‐resolution (1 mm isotropic) DTI, anatomical T1‐weighted imaging, and cognitive testing. Whole‐hippocampus, head, body, and tail subregions were manually segmented to yield DTI metrics (mean, axial, and radial diffusivities—MD, AD, and RD; fractional anisotropy—FA), volumes, and qualitative assessments of hippocampal morphology and digitations. Automated segmentation of T1‐weighted images was used to corroborate manual whole‐hippocampus volumes.ResultsGross morphology and digitation counts were similar in both groups. Whole‐hippocampus volumes were 18% smaller in the PAE than the control group on manually traced diffusion images, but automated T1‐weighted image segmentations were not significantly different. Subregion segmentation on DTI revealed reduced volumes of the body and tail, but not the head. There were no significant differences in diffusion metrics between groups for any hippocampal region. Correlations between age and volume were not significant in either group, whereas negative correlations between age and whole‐hippocampus MD/AD/RD, and head/body (but not tail) MD/AD/RD were significant in both groups. There were no significant effects of sex, group by age, or group by sex for any hippocampal metric. In controls, seven positive linear correlations were found between hippocampal volume and cognition; five of these were left lateralized and included episodic and working memory, and two were right lateralized and included working memory and processing speed. In PAE, left tail MD positively correlated with executive functioning, and right head MD negatively correlated with episodic memory.ConclusionsReductions of hippocampal volumes and altered relationships with memory suggest disrupted hippocampal development in PAE.
Comprehending the allergen repertoire of shrimp for precision molecular diagnosis of shrimp allergy
Authors: Wai Christine Y. Y. , Leung Nicki Y. H. , Leung Agnes S. Y. , Ngai Sai Ming , Pacharn Punchama , Yau Yat Sun , Rosa Duque Jaime Sou Da , Kwan Mike Y. W. , Jirapongsananuruk Orathai , Chan Wai Hung , Chua Gilbert T. , Lee Qun Ui , Piboonpocanun Surapon , Ho Po Ki , Wong Joshua S. C. , Li Shanshan , Xu Kary J. Y. , Wong Gary W. K. , Chu Ka Hou , Leung Patrick S. C. , Vichyanond Pakit , Leung Ting Fan 
Published: May 2022

AbstractBackgroundClinical management of shrimp allergy is hampered by the lack of accurate tests. Molecular diagnosis has been shown to more accurately reflect the clinical reactivity but the full spectrum of shrimp allergens and their clinical relevance are yet to be established. We therefore sought to comprehend the allergen repertoire of shrimp, investigate and compare the sensitization pattern and diagnostic value of the allergens in allergic subjects of two distinct populations.MethodsSera were collected from 85 subjects with challenge‐proven or doctor‐diagnosed shrimp allergy in Hong Kong and Thailand. The IgE‐binding proteins of Penaeus monodon were probed by Western blotting and identified by mass spectrometry. Recombinant shrimp allergens were synthesized and analyzed for IgE sensitization by ELISA.ResultsTen IgE‐binding proteins were identified, and a comprehensive panel of 11 recombinant shrimp allergens was generated. The major shrimp allergens among Hong Kong subjects were troponin C (Pen m 6) and glycogen phosphorylase (Pen m 14, 47.1%), tropomyosin (Pen m 1, 41.2%) and sarcoplasmic‐calcium binding protein (Pen m 4, 35.3%), while those among Thai subjects were Pen m 1 (68.8%), Pen m 6 (50.0%) and fatty acid‐binding protein (Pen m 13, 37.5%). Component‐based tests yielded significantly higher area under curve values (0.77–0.96) than shrimp extract‐IgE test (0.70–0.75). Yet the best component test differed between populations; Pen m 1‐IgE test added diagnostic value only in the Thai cohort, whereas sensitizations to other components were better predictors of shrimp allergy in Hong Kong patients.ConclusionPen m 14 was identified as a novel shrimp allergen predictive of challenge outcome. Molecular diagnosis better predicts shrimp allergy than conventional tests, but the relevant component is population dependent.
When sustainability managers' greenwash: SDG fit and effects on job performance and attitudes
Authors: Westerman James W. , Acikgoz Yalcin , Nafees Lubna , Westerman Jennifer 
Published: May 2022

AbstractSustainability managers represent a key stakeholder in implementing and diffusing sustainability initiatives. However, there is a significant gap in the literature examining the impact of greenwashing on sustainability managers. This research examines the effects of greenwashing on sustainability managers' job satisfaction, commitment, turnover intentions, and job performance from a social identity/person–organization (P‐O) fit perspective. Our sample consists of practicing sustainability managers (n = 125) in high‐ (77%) or mid‐level (23%) positions. Results indicate that perceived greenwashing negatively affects the attitudinal outcomes and job performance of sustainability managers. The results also indicate that for sustainability managers whose social responsibility identity is higher than that of their firm, greenwashing has a significant association with lower satisfaction and job performance and higher intentions to leave. However, for managers whose social responsibility identity is lower than that of their firm, employer greenwashing had no effect on the sustainability managers' attitudes, even though they recognized their own poor job performance. The cumulative effect may be a situation in which managers in the best position to enhance a firm's CSR leave the firm, and vice versa.
Skeletal muscle relaxant drug–drug–drug interactions and unintentional traumatic injury: Screening to detect three‐way drug interaction signals
Authors: Chen Cheng , Hennessy Sean , Brensinger Colleen M. , Dawwas Ghadeer K. , Acton Emily K. , Bilker Warren B. , Chung Sophie P. , Dublin Sascha , Horn John R. , Miano Todd A. , Pham Nguyen Thanh Phuong , Soprano Samantha E. , Leonard Charles E. 
Published: May 2022

AimThe aim of this study was to identify skeletal muscle relaxant (SMR) drug–drug–drug interaction (3DI) signals associated with increased rates of unintentional traumatic injury.MethodsWe conducted automated high‐throughput pharmacoepidemiologic screening of 2000–2019 healthcare data for members of United States commercial and Medicare Advantage health plans. We performed a self‐controlled case series study for each drug triad consisting of an SMR base‐pair (i.e., concomitant use of an SMR with another medication), and a co‐dispensed medication (i.e., candidate interacting precipitant) taken during ongoing use of the base‐pair. We included patients aged ≥16 years with an injury occurring during base‐pair‐exposed observation time. We used conditional Poisson regression to calculate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for injury with each SMR base‐pair + candidate interacting precipitant (i.e., triad) versus the SMR‐containing base‐pair alone.ResultsAmong 58 478 triads, 29 were significantly positively associated with injury; confounder‐adjusted RRs ranged from 1.39 (95% CI = 1.01–1.91) for tizanidine + omeprazole with gabapentin to 2.23 (95% CI = 1.02–4.87) for tizanidine + diclofenac with alprazolam. Most identified 3DI signals are new and have not been formally investigated.ConclusionWe identified 29 SMR 3DI signals associated with increased rates of injury. Future aetiologic studies should confirm or refute these SMR 3DI signals.
The efficacy of a transdiagnostic emotion regulation skills training in the treatment of binge‐eating disorder—Results from a randomized controlled trial
Authors: Berking Matthias , Eichler Eva , Naumann Eva , Svaldi Jennifer 
Published: May 2022

AbstractObjectivesDeficits in emotion regulation (ER) have been shown to be associated with binge‐eating disorder (BED). To further clarify the causal nature of this association, we tested whether systematically enhancing ER skills would reduce symptoms of BED.MethodsWe randomly allocated N = 101 individuals meeting the criteria for BED to a transdiagnostic ER skills training or to a waitlist control condition (WLC). Primary outcome was the reduction in binges during the treatment‐vs.‐waiting period as assessed with the Eating Disorder Examination (EDE) interview.ResultsMixed‐model ANOVAs indicated that the average pre‐to‐post decrease in binges assessed with the EDE was significantly greater in the ER skills training condition than in the WLC (d = 0.66). These effects were stable over the 6‐month follow‐up period (d = 0.72). Remission rates at post/follow‐up were 34.4/45.0% in the skills training and 7.5/20.0% in the WLC. Additionally, we found a greater reduction in general eating disorder psychopathology, of food consumption in a bogus taste test and of depression in the ER skills training condition. Moreover, the greater reduction in binge‐eating episodes in the training condition was (partially) mediated by a greater increase in ER skills.ConclusionsThe findings provide further support for the assumed importance of deficits in ER as a maintaining factor and, hence, as a target in the treatment of BED. As ER skills trainings have been shown to also reduce other kinds of psychopathology, they might be considered a promising transdiagnostic add‐on component to disorder‐specific interventions.
Subjective wellbeing and emotion regulation strategies: How are they associated with student engagement in online learning during Covid‐19?
Authors: Zhoc Karen C. H. , Cai Yuyang , Yeung S. S. , Shan Jianguo 
Published: May 2022

AbstractBackgroundThe COVID‐19 pandemic has brought unprecedented challenges to the world, creating significant impact on people's lives and subjective wellbeing. While previous studies have shown that students’ wellbeing and how they manage their emotions are critical to students’ learning, less research has considered their specific impacts on student engagement in online learning.AimsThe aim of this study is to examine how students’ subjective wellbeing and emotion regulation strategies (viz cognitive reappraisal and expressive suppression) are associated with student engagement in online learning during the pandemic.SampleA total of 965 students from a university in China participated in the study.MethodsThe data were collected online during the COVID‐19 from March to July 2020, which included measures of wellbeing, emotion regulation strategie, and online learning engagement.ResultsStructural equation modelling results showed that wellbeing was positively associated with both the use of reappraisal and suppression. Moreover, mediation analysis showed that reappraisal partially mediated the relationship between wellbeing and all types of online learning engagement (including cognitive, emotional and behavioural engagements). Conversely, suppression was found to have a small mediating effect between wellbeing and behavioural engagement of online learning only. No such effect was found on cognitive and emotional engagements.ConclusionsThe findings provide evidence on the positive relationship between wellbeing and both the strategies of suppression and reappraisal during the pandemic. However, only reappraisal has positive impact on learning, suggesting the importance of effective regulation strategies on students’ online engagement. Theoretical and practical implications of the findings are discussed.
Outcomes of Hodgkin variant Richter transformation in chronic lymphocytic leukaemia and small lymphocytic lymphoma in British Columbia
Authors: Zhu Kai , Jamroz Andrew , Huang Steven , Villa Diego , Freeman Ciara L. , Scott David W. , Slack Graham , Sehn Laurie H. , Connors Joseph M. , Toze Cynthia L. , Savage Kerry J. , Gerrie Alina S. 
Published: May 2022

SummaryHodgkin variant Richter transformation (HvRT) is a rare and challenging complication of chronic lymphocytic leukaemia (CLL) for which information on prognostic factors and treatment approaches remain limited. We analysed characteristics and survival outcomes of a population‐based cohort of 32 patients with HvRT identified in British Columbia over a 40‐year period. Median interval from CLL diagnosis to HvRT was 5.6 years (range, 0–33.6), with five cases diagnosed concurrently. Most patients (80%) had treatment for CLL prior to HvRT. Median age at HvRT was 71 years (range, 51–86) and the majority of patients had high‐risk disease, including stage 3–4 in 87% and International Prognostic Score (IPS) ≥ 4 in 65%. Two‐year progression‐free (PFS) and overall survival (OS) from HvRT were 47% (95% CI: 29%–64%) and 57% (95% CI: 38%–72%), respectively. OS from HvRT was significantly worse in those with anaemia (p = 0.02), elevated lactate dehydrogenase (p = 0.04), high IPS (p = 0.04), and worse performance status (p = 0.001). For those treated with curative‐intent ABVD/ABVD‐like therapy, 2‐year PFS and OS were 70% (95% CI: 45%–85%) and 74% (95% CI: 49%–89%), respectively. In this real‐world population‐based cohort, HvRT was associated with poor clinical outcomes overall; however, those able to tolerate curative‐intent therapy had similar survival to older patients with de novo HL.
KRAS variant allele frequency, but not mutation positivity, associates with survival of patients with pancreatic cancer
Authors: Suzuki Tatsunori , Masugi Yohei , Inoue Yosuke , Hamada Tsuyoshi , Tanaka Mariko , Takamatsu Manabu , Arita Junichi , Kato Tomotaka , Kawaguchi Yoshikuni , Kunita Akiko , Nakai Yousuke , Nakano Yutaka , Ono Yoshihiro , Sasahira Naoki , Takeda Tsuyoshi , Tateishi Keisuke , Uemura Sho , Koike Kazuhiko , Ushiku Tetsuo , Takeuchi Kengo , Sakamoto Michiie , Hasegawa Kiyoshi , Kitago Minoru , Takahashi Yu , Fujishiro Mitsuhiro ,   for the GTK Pancreatic Cancer Study Group in Japan
Published: May 2022

AbstractKRAS mutation is a major driver of pancreatic carcinogenesis and will likely be a therapeutic target. Due to lack of sensitive assays for clinical samples of pancreatic cancer with low cellularity, KRAS mutations and their prognostic association have not been fully examined in large populations. In a multi‐institutional cohort of 1162 pancreatic cancer patients with formalin‐fixed paraffin‐embedded tumor samples, we undertook droplet digital PCR (ddPCR) for KRAS codons 12/13/61. We examined detection rates of KRAS mutations by clinicopathological parameters and survival associations of KRAS mutation status. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for disease‐free survival (DFS) and overall survival (OS) were computed using the Cox regression model with adjustment for potential confounders. KRAS mutations were detected in 1139 (98%) patients. The detection rate did not differ by age of tissue blocks, tumor cellularity, or receipt of neoadjuvant chemotherapy. KRAS mutations were not associated with DFS or OS (multivariable HR comparing KRAS‐mutant to KRAS‐wild‐type tumors, 1.04 [95% CI, 0.62–1.75] and 1.05 [95% CI, 0.60–1.84], respectively). Among KRAS‐mutant tumors, KRAS variant allele frequency (VAF) was inversely associated with DFS and OS with HRs per 20% VAF increase of 1.27 (95% CI, 1.13–1.42; ptrend <0.001) and 1.31 (95% CI, 1.16–1.48; ptrend <0.001), respectively. In summary, ddPCR detected KRAS mutations in clinical specimens of pancreatic cancer with high sensitivity irrespective of parameters potentially affecting mutation detections. KRAS VAF, but not mutation positivity, was associated with survival of pancreatic cancer patients.
Alteration in Rab11‐mediated endocytic trafficking of LDL receptor contributes to angiotensin II‐induced cholesterol accumulation and injury in podocytes
Authors: Hu Jijia , Zhu Zijing , Chen Zhaowei , Yang Qian , Liang Wei , Ding Guohua 
Published: May 2022

AbstractObjectivesExposure of podocytes to angiotensin II (Ang II) enhances the abundance of the cell surface glycoprotein, low‐density lipoprotein receptor (LDLR) and promotes significant changes in the cellular cholesterol content. Recent investigation provides evidence that the small GTPase Rab11 is involved in the regulation of LDLR, but the exact mechanisms remain unknown. In this study, the role of Rab11 in post‐transcriptional regulation of LDLR was evaluated to investigate potential mechanisms of podocyte cholesterol dysregulation in chronic kidney disease.Materials and MethodsCholesterol content, LDLR and Rab11 expression were assessed in podocytes from Ang II‐infused mice. In vitro, the intracellular localization of LDLR was detected under different conditions. Rab11 expression was modulated and we then explored the effect of anti‐lipid cytotoxicity by detecting LDLR expression and trafficking, cholesterol content and apoptosis in podocytes.ResultsCholesterol accumulation, upregulated expression of LDLR and Rab11 were discovered in podocytes from Ang II‐infused mice. Ang II enhanced the co‐precipitation of LDLR with Rab11 and accelerated the endocytic recycling of LDLR to the plasma membrane. Additionally, silencing Rab11 promoted lysosomal degradation of LDLR and alleviated Ang II‐induced cholesterol accumulation and apoptosis in podocytes. Conversely, overexpression of Rab11 or inhibition of lysosomal degradation up‐regulated the abundance of LDLR and aggravated podocyte cholesterol deposition.ConclusionsRab11 triggers the endocytic trafficking and recycling of LDLR; overactivation of this pathway contributes to Ang II‐induced podocyte cholesterol accumulation and injury.
Activation of aldehyde dehydrogenase 2 protects ethanol‐induced osteonecrosis of the femoral head in rat model
Authors: Lin Xiaoyi , Zhu Daoming , Wang Kaiyang , Luo Pengbo , Rui Gang , Gao Youshui , Liu Fuan , Yu Hongping 
Published: May 2022

AbstractObjectivesOsteonecrosis of the femoral head (ONFH) is a devastating disease characterized by destructive bone structures, enlarged adipocyte accumulation and impaired vascularization. The aldehyde dehydrogenase 2 (ALDH 2) is the limiting enzyme for ethanol metabolism with many physiological functions. The aim was investigated the potential protective role of activated ALDH 2 by Alda‐1 for ethanol‐induced ONFH.Materials and MethodsThe ethanol‐induced ONFH in rat was performed to explore the protective of Alda‐1 by various experimental methods. Subsequently, the effect of Alda‐1 and ethanol on the osteogenic and adipogenic differentiation was investigated via multiple cellular and molecular methods. Finally, the effect of Alda‐1 and ethanol on the neo‐vascularization was detected in Human umbilical vein endothelial cells (HUVECs) and ONFH model.ResultsFirstly, radiographical and pathological measurements indicated that alda‐1 protected ethanol‐induced ONFH. Moreover, ethanol significantly inhibited the proliferation and osteogenic differentiation of BMSCs, whereas Alda‐1 could distinctly rescue it by PI3K/AKT signalling. Secondly, ethanol remarkably promoted the lipid vacuoles formation of BMSCs, while Alda‐1 significantly retarded it on BMSCs by AMPK signalling pathway. Finally, ethanol significantly inhibited proliferation and growth factor level resulting in reduced angiogenesis, whereas Alda‐1 could rescue the effect of ethanol. Additionally, Alda‐1 significantly reduced the occurrence of ONFH and promoted vessel number and distribution in alcoholic ONFH.ConclusionsAlda‐1 activation of ALDH 2 was highly demonstrated to protect ethanol‐induced ONFH by triggering new bone formation, reducing adipogenesis and stimulating vascularization.
The effects of human development, environmental factors, and a major highway on mammalian community composition in the Wasatch Mountains of northern Utah, USA
Authors: Barnick Kelsey A. , Green Austin M. , Pendergast Mary E. , Şekercioğlu Çağan H. 
Published: May 2022

AbstractHuman development and roads threaten wildlife through distinct mechanisms and understanding the influence of these elements can better inform mitigation and conservation strategies. We used camera traps to quantify the effects of major roads, environmental factors, and human development on the mammalian community composition between sites north and south of a major interstate highway in northern Utah, USA. We found no significant differences in species richness nor community similarity across the north–south divide of the highway. Through Bayesian hierarchical modeling, we compared the effects of the distance to the highway, housing and human population density, normalized difference vegetation index (NDVI), and the human footprint index to changes in mammalian community composition and species‐specific habitat usage. Community occupancy response, similarity, and species richness were negatively affected by increased housing and human population densities and positively affected by increased NDVI and decreased human footprint, whereas their response to the highway was more inconclusive. We conclude that mammalian community composition in our study area is influenced by both environmental conditions and human development while the effect of the highway was more nuanced, possibly due to the presence of a newly constructed wildlife overpass. Taken together, the lack of differences in species richness or community composition across the highway suggests that it may not currently exacerbate the effects of other anthropogenic sources of habitat fragmentation and highlights the need for additional research into human–wildlife conflict mitigation strategies.