bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recognizing and Acting on Mentation Concerns Caregivers are key partners in addressing depression, dementia, and delirium in older adults.
Authors: Mack Laurin , Zonsius Mary C. , Newman Michelle , Emery-Tiburcio Erin E. 
Published: November 2022

This article is the fourth in a series, Supporting Family Caregivers in the 4Ms of an Age-Friendly Health System, published in collaboration with the AARP Public Policy Institute as part of the ongoing Supporting Family Caregivers: No Longer Home Alone series. The 4Ms of an Age-Friendly Health System (What Matters, Medication, Mentation, and Mobility) is an evidence-based framework for assessing and acting on critical issues in the care of older adults across settings and transitions of care. Engaging the health care team, including older adults and their family caregivers, with the 4Ms framework can help to ensure that every older adult gets the best care possible, is not harmed by health care, and is satisfied with the care they receive.
The articles in this series present considerations for implementing the 4Ms framework in the inpatient hospital setting and incorporating family caregivers in doing so. Resources for both nurses and family caregivers, including a series of accompanying videos developed by AARP and the Rush Center for Excellence in Aging and funded by The John A. Hartford Foundation, are also provided. Nurses should read the articles first, so they understand how best to help family caregivers. Then they can refer caregivers to the informational tear sheet—Information for Family Caregivers—and instructional videos, encouraging them to ask questions. For additional information, see Resources for Nurses. Cite this article as: Mack, L., et al. Recognizing and Acting on Mentation Concerns. Am J Nurs 2022; 122(5): 50-55
Brief Report: Sex Differences in the Association Between Cerebrovascular Function and Cognitive Health in People Living With HIV in Urban China
Authors: Chow Felicia C. , Zhao Fang , He Yun , Song Xiaojing , Zhang Jiangxia , Ao Donghui , Wu Yuchen , Hou Bo , Sorond Farzaneh A. , Ances Beau M. , Letendre Scott , Heaton Robert K. , Shi Chuan , Feng Feng , Zhu Yicheng , Wang Huanling , Li Taisheng 
Published: November 2022

Background:
Cardiometabolic and cerebrovascular disease are strong independent contributors to cognitive impairment in people living with HIV. Data suggest that cardiovascular risk may play a greater role in cognitive health in women than in men with HIV.

Methods:
We performed a cross-sectional study of 104 participants with virologically suppressed HIV from 2 clinics in urban China. Participants underwent neuropsychological testing from which we calculated T scores globally and in 5 cognitive domains. We assessed cerebral vasoreactivity of the middle cerebral arteries in response to breath holding. We constructed linear regression models to determine associations between cerebrovascular and cognitive function overall and stratified by sex.

Results:
Women were younger than men (48 versus 51 years, P = 0.053), had fewer years of education (9 years versus 12 years, P = 0.004), and fewer cardiometabolic risk factors (0 versus 1 factor, P = 0.008). In a model with all participants, cerebrovascular function was significantly associated with global cognition (2.74 higher T score per 1-point higher cerebral vasoreactivity [SE 1.30], P = 0.037). Cerebrovascular function remained significantly associated with global cognition among women (4.15 higher T score [SE 1.78], P = 0.028) but not men (1.70 higher T score [SE 1.74], P = 0.33). The relationships between cerebrovascular function and specific cognitive domains followed a similar pattern, with significant associations present among women but not men.

Conclusions:
Women with well-controlled HIV may be more vulnerable to the effect of cerebrovascular injury on cognitive health than men. Studies evaluating strategies to protect against cognitive impairment in people living with HIV should include adequate representation of women and stratification of analyses by sex.
Sarcopenia in Immune-Mediated Rheumatic Diseases—Review
Authors: Santo Rafaela Cavalheiro do Espírito , Baker Joshua F. , Santos Leonardo Peterson dos , Silva Mariana Marchezan Menezes da , Xavier Ricardo Machado 
Published: November 2022

Introduction
Sarcopenia is a condition characterized by decreased muscle strength and muscle mass, which can impact physical function. Sarcopenia develops as a consequence of age-related decline (primary sarcopenia) and has a major impact on physical, social, and emotional well-being. In addition, patients with rheumatic diseases may suffer from sarcopenia independently of aging (secondary sarcopenia). Exercise, pharmacological treatments, and nutritional supplementation are some of the strategies used for the management of sarcopenia in the general population. The aim of this review is to summarize the evidence around the prevalence and impact of sarcopenia in patients with rheumatic diseases.

Conclusions
From our review, we can state that sarcopenia is a common and prevalent condition among the rheumatic diseases. Furthermore, the impacts of sarcopenia are not well-appreciated, and the implementation of treatment strategies has not been widespread. Strategies such as exercise and some pharmacological treatments are effective in improving physical and functional impairment related to these conditions.

Future Research Directions in the Field
New pharmacological treatments are being actively studied and may contribute in the future to the management of sarcopenia.
Effect of tranexamic acid on endothelial von Willebrand factor/ADAMTS-13 response to in vitro shock conditions
Authors: Diebel Lawrence N. , Liberati David M. 
Published: November 2022

BACKGROUND
Traumatic/hemorrhagic shock, sepsis and other inflammatory processes lead to endothelial activation and a loss of the endothelial glycocalyx. von Willebrand factor (vWF) is an acute phase reactant that is released from endothelial cells and megakaryocytes. Stimulated but not basal vWF leads to significant formation of ultralarge multimers (ultralarge vWF [ULvWF]) and risk for thrombotic complications. Ultralarge vWF is cleaved by a disintegrin and metalloproteinase with a thrombospondin type motif 13 (ADAMTS 13); alterations in ULvWF/ADAMTS 13 ratio may contribute to trauma-induced coagulopathy. Salutary effects of tranexamic acid (TXA) on trauma-induced coagulopathy have been described. These effects appear apart from antifibrinolytic actions of TXA and include protection of the endothelial glycocalyx. Ultralarge vWF is in part anchored to the glycocalyx layer of the endothelium. Tranexamic acid protected the endothelial glycocalyx layer from degradation using a microfluidic model of the microcirculation subjected to hypoxia-reoxygenation and catecholamine excess. We hypothesized that TXA administration following shock conditions would impact the vWF-ADAMTS-13 axis by protecting the glycocalyx from degradation. This was studied in a endothelial microfluidic flow study.

METHODS
Human umbilical vein endothelial cells were established under flow conditions and subjected to biomimetic shock. Tranexamic acid was added after 90 minutes of perfusion. von Willebrand factor antigen and ADAMTS-13 activity were measured. Western blot analysis was performed for vWF characterization from perfusion media.

RESULTS
Shock conditions increased vWF antigen and decreased ADAMTS 13 activity. Tranexamic acid ameliorated shock induced cleavage in the ADAMTS 13-vWF axis with a reduction of the thrombogenic ULvWF.

CONCLUSION
These results suggest another mechanism whereby administration of TXA early following traumatic/hemorrhagic shock mitigates microvascular perfusion abnormalities and subsequent organ failure. The resultant effects on platelet adhesion and aggregation require further study.
The Effect of Nursing Discharge Planning Program to Prevent Recurrent Falls, Readmission, and Length of Hospital Stay in the Aged Patients
Authors: Dadgari Ali , Rahmani Parvaneh , Mirrezaie Seyed Mohammad 
Published: November 2022

Background and Purpose:
One of the interventions that can be effective in preventing recurrence and readmission due to falls is the use of nursing discharge planning program. The aim of this study was to determine the effect of nursing discharge planning program in preventing recurrent falls and readmission in the elderly referred to the trauma center.

Methods:
The study was a parallel randomized controlled trial. The data were collected from hospital electronic data, patients' self-report, and injury severity scale. In this study, participants (n = 169) were divided into 2 groups using an Excel-generated random sequence. In the experimental group, a discharge planning program was applied. Individualized training with a booklet for the patient and his primary caregiver was conducted for 4 sessions; each session lasted 30 to 60 minutes. The participants were followed for 6 months.

Results:
The mean and standard deviation of the participants' age were 76 ± 10 years. Prior to implementation of the program, the participants in the control and intervention groups did not differ significantly in age, independence, cognitive status, and severity of the injury. Postimplementation of discharge planning program, a significant decrease in falls (P < .049), hospitalization readmission (P < .014), length of hospital stay (P < .018), and severity of injury (P < .00) were observed in the intervention group compared with the control group.

Discussion and Conclusions:
Participants in the discharge planning program experienced lower severity of injury in the subsequent episode of falls. In addition, subjects' readmission and hospital stay were shorter in the experimental group. Discharge planning program is recommended to be implemented in other age-related distributions.
Stricker Learning Span criterion validity: a remote self-administered multi-device compatible digital word list memory measure shows similar ability to differentiate amyloid and tau PET-defined biomarker groups as in-person Auditory Verbal Learning Test
Authors: Stricker Nikki H. , Stricker John L. , Frank Ryan D. , Fan Winnie Z. , Christianson Teresa J. , Patel Jay S. , Karstens Aimee J. , Kremers Walter K. , Machulda Mary M. , Fields Julie A. , Graff-Radford Jonathan , Jack Clifford R. , Knopman David S. , Mielke Michelle M. , Petersen Ronald C. 
Published: November 2022

AbstractObjectiveThe Stricker Learning Span (SLS) is a computer-adaptive digital word list memory test specifically designed for remote assessment and self-administration on a web-based multi-device platform (Mayo Test Drive). We aimed to establish criterion validity of the SLS by comparing its ability to differentiate biomarker-defined groups to the person-administered Rey’s Auditory Verbal Learning Test (AVLT).Participants and MethodsParticipants (N=353; mean age=71, SD=11; 93% cognitively unimpaired [CU]) completed the AVLT during an in-person visit, the SLS remotely (within 3 months) and had brain amyloid and tau PET scans available (within 3 years). Overlapping groups were formed for 1) those on the Alzheimer’s disease (AD) continuum (amyloid PET positive, A+, n=125) or not (A-, n=228), and those with biological AD (amyloid and tau PET positive, A+T+, n=55) vs no evidence of AD pathology (A-T-, n=195). Analyses were repeated among CU participants only.ResultsThe SLS and AVLT showed similar ability to differentiate biomarker-defined groups when comparing AUROCs (p’s>.05). In logistic regression models, SLS contributed significantly to predicting biomarker group beyond age, education and sex, including when limited to CU participants. Medium (A- vs A+) to large (A-T- vs A+T+) unadjusted effect sizes were observed for both SLS and AVLT. Learning and delay variables were similar in terms of ability to separate biomarker groups.ConclusionsRemotely administered SLS performed similarly to in-person-administered AVLT in its ability to separate biomarker-defined groups, providing evidence of criterion validity. Results suggest the SLS may be sensitive to detecting subtle objective cognitive decline in preclinical AD.
ClinVar and HGMD genomic variant classification accuracy has improved over time, as measured by implied disease burden
Authors: Sharo Andrew G. , Zou Yangyun , Adhikari Aashish N. , Brenner Steven E. 
Published: November 2022

AbstractCurated databases of genetic variants assist clinicians and researchers in interpreting genetic testing results. Yet these databases contain variants misclassified as pathogenic, which do not result in pathogenic phenotypes. Using archives of ClinVar and HGMD, we investigated how variant misclassification has changed over six years across different ancestry groups. We considered inborn errors of metabolism (IEMs) screened in newborns as a model system because these disorders are often highly penetrant with neonatal phenotypes. We used samples from the 1000 Genomes Project (1KGP) to identify individuals with genotypes that were classified by the databases as pathogenic. Due to the rarity of IEMs, nearly all such classified pathogenic genotypes indicate likely variant misclassification in ClinVar or HGMD. While the false positive rate of both ClinVar and HGMD have improved over time, HGMD variants currently would imply two orders of magnitude more affected individuals in 1KGP than ClinVar variants. We observed that African ancestry individuals have a significantly increased chance of being incorrectly indicated to be affected by a screened IEM when HGMD variants are used. However, this bias affecting genomes of African ancestry was no longer significant once common variants were removed in accordance with recent variant interpretation guidelines. We discovered that ClinVar variants classified as Pathogenic or Likely Pathogenic are reclassified 11-fold more often than DM or DM? variants in HGMD, which has likely resulted in ClinVar’s lower false positive rate. Considering misclassified variants that have since been reclassified, we found that variant interpretation guidelines and allele frequency databases comprised of genetically diverse samples are important factors in reclassification. Finally, we find that ClinVar variants common in European and South Asian individuals were more likely to be reclassified to a lower confidence category, perhaps due to an increased chance of these variants being classified by multiple submitters.
A quantitative tool for seizure severity: diagnostic and therapeutic applications
Authors: Pattnaik Akash R. , Ghosn Nina J. , Ong Ian Z. , Revell Andrew Y. , Ojemann William K.S. , Scheid Brittany H. , Bernabei John M. , Conrad Erin , Sinha Saurabh R. , Davis Kathryn A. , Sinha Nishant , Litt Brian 
Published: November 2022

AbstractObjectiveMore than one-third of the people with focal epilepsy do not achieve seizure freedom with medication, neuromodulation, or neurosurgery therapies. Palliative care with the goal of reducing epilepsy burden is an alternative for these patients. Minimizing severe seizures is essential for reducing morbidity. Existing seizure severity scales are qualitative and rely on patient reports, limiting our ability to rigorously track and intervene to curb severe seizures. The goal of this study is to develop and validate a quantitative metric for seizure severity.MethodsWe retrospectively analyzed preictal and ictal intracranial-EEG (iEEG) recordings from 54 people with drug-resistant epilepsy undergoing pre-surgical evaluation. We developed a new metric that objectively combines seizure duration, spread, and semiology to quantify seizure severity. We calculated preictal iEEG network features and fit a linear mixed-effects model to quantify patient-specific associations between preictal networks and seizure severity.ResultsWe evaluated 256 seizures from 54 patients using the quantitative seizure severity score. Seizure severity was consistent with clinical seizure type. Medication taper strategy was associated with seizure severity (p = 0.018, 97.5% confidence interval = [-1.242, -0.116]) and lower pre-surgical seizure severity was associated with better post-surgical seizure outcome (U = 465,p= 0.042). A linear mixed-effects model with preictal network features as regressors and seizure severity as response revealed a group-level positive trend. In 12 out of 14 patients with multiple types of seizures, more severe seizures were preceded by more abnormal preictal networks.SignificanceWe present a quantitative metric for seizure severity that correlates with clinical and electrographic features. We found that the seizure severity score was associated with abnormal preictal networks. We propose this measure to holistically capture patient condition and guide incremental changes in therapy to improve patient outcome over time.
Near-infrared II hyperspectral imaging improves the accuracy of pathological sampling of multiple cancer specimens
Authors: Zhang Lingling , Liao Jun , Wang Han , Zhang Meng , Han Dandan , Jiang Chen , Jia Zhanli , Liu Yao , Qin Chenchen , Niu ShuYao , Bu Hong , Yao Jianhua , Liu Yueping 
Published: November 2022

AbstractPathological histology is the clinical gold standard for cancer diagnosis. Incomplete or excessive sampling of the formalin-fixed excised cancer specimen will result in inaccurate histology assessment or excessive workload. Conventionally, pathologists perform specimen sampling relying on naked-eye observation which is subjective and limited by human perception. Precise identification of tumor beds, size, and margin is challenging, especially for lesions with inconspicuous tumor beds. To break the limits of human eye perception (visible: 400-700 nm) and improve the sampling efficiency, in this study, we propose using a second near-infrared window (NIR-II: 900-1700 nm) hyperspectral imaging (HSI) system to assist specimen sampling on the strength of the verified deep anatomical penetration and low scattering characteristics of the NIR-II optical window. We use selected NIR-II HSI narrow bands to synthesize color images for human eye observation and also apply artificial intelligence (AI)-based algorithm on the complete NIR-II HSI data for automatic tissue classification to assist doctors in specimen sampling. Our study employing 5 pathologists, 92 samples and 7 cancer types shows that NIR-II HSI-assisted methods have significant improvements in determining tumor beds compared with conventional methods (Conventional color image with or without X-ray). The proposed system can be easily integrated into the current workflow, and has high imaging efficiency and no ionizing radiation. It may also find applications in intraoperative detection of residual lesions and identification of different tissues.
Improved prediction of blood biomarkers using deep learning
Authors: Sigurdsson Arnór I. , Ravn Kirstine , Winther Ole , Lund Ole , Brunak Søren , Vilhjálmsson Bjarni J. , Rasmussen Simon 
Published: November 2022

ABSTRACTBlood and urine biomarkers are an essential part of modern medicine, not only for diagnosis, but also for their direct influence on disease. Many biomarkers have a genetic component, and they have been studied extensively with genome-wide association studies (GWAS) and methods that compute polygenic scores (PGSs). However, these methods generally assume both an additive allelic model and an additive genetic architecture for the target outcome, and thereby risk not capturing non-linear allelic effects nor epistatic interactions. Here, we trained and evaluated deep-learning (DL) models for PGS prediction of 34 blood and urine biomarkers in the UK Biobank cohort, and compared them to linear methods. For lipid traits, the DL models greatly outperformed the linear methods, which we found to be consistent across diverse populations. Furthermore, the DL models captured non-linear effects in covariates, non-additive genotype (allelic) effects, and epistatic interactions between SNPs. Finally, when using only genome-wide significant SNPs from GWAS, the DL models performed equally well or better for all 34 traits tested. Our findings suggest that DL can serve as a valuable addition to existing methods for genotype-phenotype modelling in the era of increasing data availability.
Association of genetic variation at the GJA5/ACP6 locus with motor progression in Parkinson’s
Authors: Martinez-Carrasco Alejandro , Real Raquel , Lawton Michael , Reynolds Regina H , Tan Manuela M. X. , Wu Lesley , Williams Nigel M. , Carroll Camille , Corvol Jean-Christophe , Hu Michele T.M. , Grosset Donald G. , Hardy John , Ryten Mina , Ben-Shlomo Yoav , Shoai Maryam , Morris Huw R. 
Published: November 2022

ABSTRACTImportanceThere is a pressing need to understand the biology of Parkinson’s disease (PD) progression and to identify biological pathways as possible therapeutic targets.ObjectiveTo identify genomic variation associated with PD motor presentation and early stage progression.DesignGWAS meta-analysis of early PD motor progression, from multiple longitudinal cohorts, using MDS-UPDRS III clinical assessments.SettingMulticentreParticipants3572 unrelated European ancestry individuals diagnosed with PD from 6 studies.Main Outcomes and MeasuresLinear mixed effect models under an additive model corrected for age at diagnosis, gender, and the first 5 genetic principal components (PCs), with axial, limb, and total MDS-UPDRS III as outcomes of the model.ResultsWe identified an association between the PD axial rate of progression and variation at theGJA5locus at 1q12 (Beta = -0.25, SE = 0.04,P= 3.4e-10). Exploration of the regulation of gene expression in the region (cis-eQTL analysis) showed that the lead variant was associated with expression ofACP6, a lysophosphatidic acid phosphatase that regulates mitochondrial lipid biosynthesis (cis-eQTLs p-values in blood and brain RNA expression datasets: < 10−8in eQTLGen and 10−7in PsychEncode). In addition, we found a nominal association between axial motor presentation and theMAD1L1gene at 7q21.11 (Beta = 0.54, SE = 0.11,P= 1.6e-7), a gene previously associated with neuropsychiatric disease, and in the long non-coding RNALINC00511at 17q21.31 (Beta = -0.62, SE = 0.11,P= 6.3e-8). Further functional annotation allowed us to nominate the likely causal variants and determine that variants at 7q21.11 may be related to dysregulation ofMAD1L1expression. Variants atLINC00511may cause a disruption of a distal epigenetic regulation ofSOX9through an anchored chromatin loop.Conclusions and RelevanceOur large multicentre study sheds new light on the genetic architecture of PD progression, which is distinct from PD susceptibility. Our study highlights the potential role of mitochondrial lipid homeostasis in the progression of PD, which may be important in establishing new drug targets to tackle disease progression.
An implementation framework to improve the transparency and reproducibility of computational models of infectious diseases
Authors: Pokutnaya Darya , Childers Bruce , Arcury-Quandt Alice , Hochheiser Harry , Van Panhuis Willem G 
Published: November 2022

AbstractComputational models of infectious diseases have become valuable tools for research and the public health response against epidemic threats. The reproducibility of computational models has been limited, undermining the scientific process and possibly trust in modeling results and related response strategies, such as vaccination. We translated published reproducibility guidelines from a wide range of scientific disciplines into an implementation framework for improving reproducibility of infectious disease computational models. The framework comprises twenty-two elements that should be described, grouped into six categories: computational environment, analytical software, model description, model implementation, data, and experimental protocol. The framework can be used by scientific communities to develop actionable tools for sharing computational models in a reproducible way.