bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel age-informed approach for genetic association analysis in Alzheimer’s disease
Authors:   for the Alzheimer’s Disease Neuroimaging Initiative, Le Guen Yann , Belloy Michael E. , Napolioni Valerio , Eger Sarah J. , Kennedy Gabriel , Tao Ran , He Zihuai , Greicius Michael D. 
Published: April 2021

AbstractBackgroundMany Alzheimer’s disease (AD) genetic association studies disregard age or incorrectly account for it, hampering variant discovery.MethodsUsing simulated data, we compared the statistical power of several models: logistic regression on AD diagnosis adjusted and not adjusted for age; linear regression on a score integrating case-control status and age; and multivariate Cox regression on age-at-onset. We applied these models to real exome-wide data of 11,127 sequenced individuals (54% cases) and replicated suggestive associations in 21,631 genotype-imputed individuals (51% cases).ResultsModeling variable AD risk across age results in 5–10% statistical power gain compared to logistic regression without age adjustment, while incorrect age adjustment leads to critical power loss. Applying our novel AD-age score and/or Cox regression, we discovered and replicated novel variants associated with AD onKIF21B, USH2A, RAB10, RIN3, andTAOK2genes.ConclusionOur AD-age score provides a simple means for statistical power gain and is recommended for future AD studies.
An integrative multi-omics approach reveals new central nervous system pathway alterations in Alzheimer’s disease
Authors: Clark Christopher , Dayon Loïc , Masoodi Mojgan , Bowman Gene L. , Popp Julius 
Published: April 2021

Abstract
Background
Multiple pathophysiological processes have been described in Alzheimer’s disease (AD). Their inter-individual variations, complex interrelations, and relevance for clinical manifestation and disease progression remain poorly understood. We hypothesize that specific molecular patterns indicating both known and yet unidentified pathway alterations are associated with distinct aspects of AD pathology.

Methods
We performed multi-level cerebrospinal fluid (CSF) omics in a well-characterized cohort of older adults with normal cognition, mild cognitive impairment, and mild dementia. Proteomics, metabolomics, lipidomics, one-carbon metabolism, and neuroinflammation related molecules were analyzed at single-omic level with correlation and regression approaches. Multi-omics factor analysis was used to integrate all biological levels. Identified analytes were used to construct best predictive models of the presence of AD pathology and of cognitive decline with multifactorial regression analysis. Pathway enrichment analysis identified pathway alterations in AD.

Results
Multi-omics integration identified five major dimensions of heterogeneity explaining the variance within the cohort and differentially associated with AD. Further analysis exposed multiple interactions between single ‘omics modalities and distinct multi-omics molecular signatures differentially related to amyloid pathology, neuronal injury, and tau hyperphosphorylation. Enrichment pathway analysis revealed overrepresentation of the hemostasis, immune response, and extracellular matrix signaling pathways in association with AD. Finally, combinations of four molecules improved prediction of both AD (protein 14-3-3 zeta/delta, clusterin, interleukin-15, and transgelin-2) and cognitive decline (protein 14-3-3 zeta/delta, clusterin, cholesteryl ester 27:1 16:0 and monocyte chemoattractant protein-1).

Conclusions
Applying an integrative multi-omics approach we report novel molecular and pathways alterations associated with AD pathology. These findings are relevant for the development of personalized diagnosis and treatment approaches in AD.
The use of multimodal imaging in the evaluation of a patient with central retinal artery occlusion in the setting of asteroid hyalosis: a case report
Authors: Janetos Timothy M. , German Olga , Mirza Rukhsana 
Published: April 2021

Abstract
Background
A central retinal artery occlusion (CRAO) is an ophthalmic emergency due to its strong association with cerebrovascular and cardiovascular morbidity and mortality. A timely diagnosis is necessary but difficult in the setting of dense asteroid hyalosis, as typical fundoscopic findings can be obscured. We present a case where multimodal imaging in an eye with an obscured fundus could lead to timely diagnosis and management of CRAO in a patient with acute vision loss.

Case presentation
A 94-year-old Caucasian woman with a history of exudative macular degeneration presented to the retina clinic with acute vision loss in one eye over the course of an afternoon. The patient had dense asteroid hyalosis, and a direct retinal exam was not possible. Multimodal imaging suggested a CRAO diagnosis. The patient received digital ocular massage directly prior to undergoing fluorescein angiography (FANG), which confirmed the diagnosis. The patient was transported from clinic to the emergency room for an emergency stroke workup, which revealed a spontaneous echo in the left atrial appendage, and the patient was started on antiplatelet therapy. When she presented for follow-up within a week, the patient noted that her vision had improved at the time of digital ocular massage and continued to improve thereafter. Her FANG showed marked reperfusion of the retina, and she subsequently has completely regained her baseline visual acuity.

Conclusions
Multimodal imaging is useful in evaluating visual loss in patients with acute vision loss. In addition, ocular massage is a simple, low-risk intervention that may have benefit in the treatment of acute CRAO. Patients who present to ophthalmologists with an acute CRAO need an emergency referral for evaluation of cerebrovascular and cardiovascular comorbidities.
Community readiness for collecting stray dogs in Aradan County: a quantitative‐qualitative study
Authors: Kamalikhah Tahereh , Mirrezaei Somayeh , Rahimi Tahereh , Sabzmakan Leila , Ghobakhloo Safiye 
Published: April 2021

Abstract
Background
Paying more attention to free-roaming dogs’ population control seems to be necessary because of public health and environmental problems. The present study used the community readiness model to determine the readiness of Aradan County in terms of collecting stray dogs.

Methods
This study is a quantitative-qualitative research study conducted in Aradan County in Semnan Province of Iran. The semi-structured questionnaire uses the six dimensions of the Community Readiness Model as guideline, with 36 items used for the interview. The interviews lasted 45 to 100 minutes with 11 key members including the governor, prefect, mayor’s assistant, city council chairman, key trustees, officials responsible for environmental health network, officials responsible for environmentalism of the city, and governors of a rural district. In quantitative part two, assessors read the interviews carefully and assigned scores based on the rating-scale form suggested by the guideline itself for scoring each dimension. A qualitative directed content analysis with deductive approach was used for analyzing the collected qualitative data.

Results
The study involved 11 key members of Aradan County, all of whom were male. Most of the participants were over 40 years old and with five years of work experience (73.6 %). The mean score of each six dimensions in Aradan County were: Community efforts (4.78), Community knowledge of efforts (4.28), Leadership (4.90), Community climate (4.38), Community knowledge about the issue (4.20) and Resources related to the issue (3.29) respectively. Community readiness in Aradan County and Aradan City was generally estimated to be in the preplanning stage, whereas vague public awareness was found in the rural areas.
In the qualitative part, 870 initial open codes, 589 refund codes, 19 subcategories and 6 themes emerged, including (a) community efforts, (b) community knowledge of the efforts (c) leadership, (d) community climate, (e) community knowledge of the issue, and (f) resources related to the issue.

Conclusions
For improving the process of collecting the stray dogs, it is necessary to focus on holding educational sessions for the public to increase their partnership and justify the responsible organizations’ activities to collaborate and provide the necessary financial resources.
Combined effects of composting and antibiotic administration on cattle manure–borne antibiotic resistance genes
Authors: Keenum Ishi , Williams Robert K. , Ray Partha , Garner Emily D. , Knowlton Katharine F. , Pruden Amy 
Published: April 2021

Abstract
Background
Research is needed to delineate the relative and combined effects of different antibiotic administration and manure management practices in either amplifying or attenuating the potential for antibiotic resistance to spread. Here, we carried out a comprehensive parallel examination of the effects of small-scale (> 55 °C × 3 days) static and turned composting of manures from dairy and beef cattle collected during standard antibiotic administration (cephapirin/pirlimycin or sulfamethazine/chlortetracycline/tylosin, respectively), versus from untreated cattle, on “resistomes” (total antibiotic resistance genes (ARGs) determined via shotgun metagenomic sequencing), bacterial microbiota, and indicator ARGs enumerated via quantitative polymerase chain reaction. To gain insight into the role of the thermophilic phase, compost was also externally heated to > 55 °C × 15 days.

Results
Progression of composting with time and succession of the corresponding bacterial microbiota was the overarching driver of the resistome composition (ANOSIM; R = 0.424, p = 0.001, respectively) in all composts at the small-scale. Reduction in relative abundance (16S rRNA gene normalized) of total ARGs in finished compost (day 42) versus day 0 was noted across all conditions (ANOSIM; R = 0.728, p = 0.001), except when externally heated. Sul1, intI1, beta-lactam ARGs, and plasmid-associated genes increased in all finished composts as compared with the initial condition. External heating more effectively reduced certain clinically relevant ARGs (blaOXA, blaCARB), fecal coliforms, and resistome risk scores, which take into account putative pathogen annotations. When manure was collected during antibiotic administration, taxonomic composition of the compost was distinct according to nonmetric multidimensional analysis and tet(W) decayed faster in the dairy manure with antibiotic condition and slower in the beef manure with antibiotic condition.

Conclusions
This comprehensive, integrated study revealed that composting had a dominant effect on corresponding resistome composition, while little difference was noted as a function of collecting manure during antibiotic administration. Reduction in total ARGs, tet(W), and resistome risk suggested that composting reduced some potential for antibiotic resistance to spread, but the increase and persistence of other indicators of antibiotic resistance were concerning. Results indicate that composting guidelines intended for pathogen reduction do not necessarily provide a comprehensive barrier to ARGs or their mobility prior to land application and additional mitigation measures should be considered.
Management of sudden sensorineural hearing loss among primary care physicians in Canada: A survey study
Authors: Ng Benjamin , Crowson Matthew G. , Lin Vincent 
Published: April 2021

Background Sudden Sensorineural Hearing Loss (SSNHL) is a medical emergency requiring immediate attention as delayed treatment can lead to permanent and devastating consequences. Primary care physicians are likely the first to be presented with SSNHL and therefore have the crucial role of recognizing it and initiating timely and appropriate management. The aim of this study was to gain insight into the current knowledge and practice trends pertaining to the diagnosis and management of SSNHL among family physicians in Canada. Methods An 18-question survey targeting Canadian family physicians was marketed through two, physician-only discussion groups on the social media platform Facebook. Responses were collected between August 1st and December 22nd 2019 then aggregated and quantified. Results 52 family physicians submitted responses. 94.2% ( n = 49) reported that in their practice, unilateral SSNHL warrants urgent referral to otolaryngology and 84.6% ( n = 44) reported that unilateral sudden-onset hearing loss warrants urgent referral for audiological testing. 73.1% of participants ( n = 38) reported that they would attempt to differentiate between conductive and sensorineural hearing loss if presented with unilateral, acute or sudden-onset hearing loss. 61.5% ( n = 32) would rely on tuning fork tests to inform management decisions, as compared to 94.2% ( n = 49) relying on case history and 88.5% ( n = 46) on otoscopy. 76.9% ( n = 40) would prescribe corticosteroids if presented with confirmed, unilateral SSNHL. Conclusion The majority of family physicians in the study would make appropriate referral and treatment decisions in the management of SSNHL, understanding it is a medical emergency. Tuning fork tests are under-utilized for informing management decisions compared to other means of differentiating conductive and sensorineural hearing loss. Further research is needed to understand why some family physicians do not prescribe corticosteroids for treatment of SSNHL, which may then identify any gaps in knowledge or inform improvements in clinical protocol. Graphical Abstract
Neuropathological and behavioral characterization of aged Grn R493X progranulin-deficient frontotemporal dementia knockin mice
Authors: Frew Jonathan , Nygaard Haakon Berge 
Published: April 2021

AbstractFrontotemporal lobar degeneration (FTLD) causes a spectrum of clinical presentations of frontotemporal dementia (FTD), including progressive changes in behavior, personality, executive function, and language. Up to 20% of familial FTLD cases are caused by progranulin (GRN) haploinsufficiency (FTD-GRN), with one of the most common causal variant being a nonsense mutation at arginine 493 (R493X). Recently, a genetic knockin FTD-GRNmouse model was generated bearing thisGrnR493Xmutation, at the analogous arginine in murineGrn. Aged, homozygousGrnR493Xmice (GrnR493X/R493X) have been shown to phenotypically replicate several neuropathological hallmarks previously demonstrated inGrnnull mice. We conducted a comprehensive neuropathological and behavioral assessment of 18 month oldGrnR493X/R493Xmice, observing a striking lysosomal dysfunction and thalamic neurodegeneration not previously described in this model, as well as a male-specific increase in generalized anxiety. These findings provide additional phenotypic markers of pathogenesis in agedGrnR493X/R493Xmice that will contribute to better defining mechanisms underlying FTD-GRN, and offer relevant outcome measures for preclinical efficacy testing of novel therapeutics that target nonsense mutations leading to this devastating disease.
Arsenic in the Pearl River Delta and its related waterbody, South China: occurrence and sources, a review
Authors: Luo Chen , Routh Joyanto , Luo Dinggui , Wei Lezhang , Liu Yu 
Published: April 2021

AbstractThe Pearl River Delta (PRD) is a densely populated special economic zone in South China where rapid development since the late 1990s coincided with an increase of many environmental problems in recent years. One of these concerns is the high concentration of arsenic (As; up to 300 μg/L in groundwater) that has been documented in the PRD. Likewise, in surface water and soils, As levels are comparatively higher than in other places in China. Arsenic is discharged from various geogenic sources and anthropogenic activities along the river courses before it drains into the Pearl River Estuary. In general, relatively low As concentrations in the river are due to the limited input from weathering of parent rocks. In contrast, where mining is an important industry, As levels in the surroundings are higher, exceeding the national and international standards for drinking water and soil. The presence of sulfide ores and mining operations, such as extraction of heavy metals and disposal of mine tailings, are most likely responsible for the sharp increase of As above background levels in several tributaries draining into the Pearl River. Besides, in the middle and lower reaches of the tributaries, other anthropogenic sources, e.g., industrial effluents and domestic sewage discharge play an important role in increasing As levels. Finally, rice cultivated in the contaminated areas accumulates As and poses a health risk to the local people in the watershed.
Validity of the French version of Catquest-9SF and use of an electronic notepad for entering patient-reported outcome measures
Authors: Katz Gregory , Rouquette Alexandra , Lignereux François , Mourgues Thierry , Weber Michel , Lundström Mats 
Published: April 2021

Abstract
Background
The Catquest-9SF questionnaire is a patient reported outcome measure that quantifies the visual benefits from cataract surgery. The purpose of this study was to translate and adapt the Catquest-9SF questionnaire for France, to assess its psychometric properties via Rasch analysis, and to assess its validity when completed using an electronic notepad.

Methods
The Catquest-9SF questionnaire was translated following the guidelines of the International Society for Pharmacoeconomics and Outcomes Research. Catquest-9SF and clinical data were collected from patients before and after routine cataract surgery. All questionnaire data were collected via an electronic notepad. Rasch analysis was performed to assess psychometric properties, and sensitivity to change was analysed for patients with complete paired pre- and post-operative questionnaires.

Results
A complete filled-in preoperative questionnaire was obtained for 848 patients. Rasch analysis showed good precision (person separation: 2.32, person reliability: 0.84), ordered category probability curves, no item misfit, and unidimensionality. The respondents were slightly more able than the level of item difficulty (targeting: −1.12 logits). Sensitivity was analysed on 211 paired questionnaires, and the postoperative questionnaires showed a clear ceiling effect. The effect size was 2.6. The use of an electronic notepad for completing the questionnaire worked out very well after some adjustments.

Conclusions
The French version of Catquest-9SF has good psychometric properties and is suitable for use in French-speaking patients. The use of the Catquest-9SF questionnaire in an electronic format showed good validity.
Endodontic remnants are found more than other radiopacities in proposed implant sites
Authors: Marzook Hamdy A. M. , Yousef Eman A. , Elgendy Abeer A. 
Published: April 2021

Abstract
Background
Foreign bodies may be a cause of concern in dental implant failure.

Purpose
The aim of the present study was to assess the occurrence and to evaluate the types of radiopacities in dental extraction sites using cone beam computed tomography (CBCT).

Materials and methods
The incidence, location, and types of radiopacities were evaluated in 180 CBCT scans.

Results
Different radiopaque structures could be noted in 84 scans. Foreign bodies and remaining roots were frequently seen. Most of the radiopacities were attributed to remaining endodontic filling in upper and lower jaws in 25 scans in different locations. Remaining roots could be detected in 20 scans. Focal and diffuse radiopaque bony lesions were observed in 16 scans. Tissue response in the form of radiolucency could be seen more with endodontic foreign bodies. Tissue reactions to radiopaque filling remnants were seen in 6.11% of cases.

Conclusions
Foreign body remnants, mostly of endodontic fillings, were frequently seen in CBCT in upper and lower jaws. Evidence of tissue reactions to extraction remnants could be found. Endodontic filling remnants could be seen more in the upper jaw. Thorough examination of implant site for the presence of endodontic foreign body remnants should be stressed. Debridement of the extraction socket should be done carefully in endodontically treated teeth.
Impact of a clinical pharmacist on ultrasound-guided venous thromboembolism screening in hospitalized COVID-19 patients: a pilot prospective study
Authors: Gillespie Laura , Khan Rashid Z. , Stillson John E. , Bunch Connor M. , Shariff Faisal Salim , Speybroeck Jacob , Grisoli Anne , Schmidt Meredith Wierman , Phyu Htay , Jablonski Jason , Wells Byars , Fulkerson Daniel H. , Oancea Lyndsay , Leiser Abraham , Walsh Mark 
Published: April 2021

AbstractBackgroundThe recognition, prevention and treatment of venous thromboembolism (VTE) remains a major challenge in the face of the recent COVID-19 pandemic which has been associated with significant cardiovascular, renal, respiratory and hematologic complications related to hypercoagulability. There has been little literature thus far on the utility of screening ultrasound and the role of the clinical pharmacist in treating these patients.MethodsWe present a prospective pilot program of thirty-one consecutive COVID-19 patients who were provided four extremity screening ultrasounds for VTE on admission. This was coordinated by a clinical pharmacist as part of a multidisciplinary approach. Quantitative and qualitative data were recorded with the goal of describing the utility of the clinical pharmacist in ultrasound screening. Data collected include demographics, information on clinical symptoms or signs at presentation, and laboratory and radiologic results during the hospitalization from each individual electronic medical record.ResultsNine of the thirty-one patients presented with VTE. Of the nine patients, there were twenty-two total clotted vessels, all of which were asymptomatic. The clinical pharmacist, as the coordinator for a multidisciplinary COVID-19 associated coagulopathy management team, drafted a screening and treatment protocol for anticoagulation prophylaxis and therapy of VTE after ultrasound findings.ConclusionVTE screening of hospitalized COVID-19 patients reveals a significant number of asymptomatic VTEs and justifies diagnostic, prophylactic, and treatment measures coordinated by a clinical pharmacist.
Methodological Considerations for Furthering the Understanding of Constraints in Applied Sports
Authors: Browne Peter , Sweeting Alice J. , Woods Carl T. , Robertson Sam 
Published: April 2021

AbstractCommonly classified as individual, task or environmental, constraints are boundaries which shape the emergence of functional movement solutions. In applied sport, an ongoing challenge is to improve the measurement, analysis and understanding of constraints to key stakeholders. Methodological considerations for furthering these pursuits should be centred around an interdisciplinary approach. This integration of methodology and knowledge from different disciplines also encourages the sharing of encompassing principles, concepts, methods and data to generate new solutions to existing problems. This narrative review discusses how a number of rapidly developing fields are positioned to help guide, support and progress an understanding of sport through constraints. It specifically focuses on examples from the fields of technology, analytics and perceptual science. It discusses how technology is generating large quantities of data which can improve our understanding of how constraints shape the movement solutions of performers in training and competition environments. Analytics can facilitate new insights from numerous and complex data through enhanced non-linear and multivariate analysis techniques. The role of the perceptual sciences is discussed with respect to generating outputs from analytics that are more interpretable for the end-user. Together, these three fields of technology, analytics and perceptual science may enable a more comprehensive understanding of constraints in sports performance.