bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Results of an Implementation Plan for High-Intensity Gait Training
Authors: Moore Jennifer L. , Bø Elisabeth , Erichsen Anne , Rosseland Ingvild , Halvorsen Joakim , Bratlie Hanne , Hornby T. George , Nordvik Jan Egil 
Published: August 2021

Background and Purpose:
High-intensity gait training is recommended in stroke rehabilitation to improve gait speed, walking distance, and balance. However, identifying effective and efficient implementation methods is a challenge for rehabilitation providers. This article describes the development of an implementation plan, presents findings of each implementation phase, and identifies the project's impact on clinicians and the health system.

Methods:
Two inpatient rehabilitation facilities, including 9 physical therapists, collaborated with a knowledge translation center to implement this program. We developed an implementation plan using the Knowledge-to-Action Framework and utilized the Consolidated Framework for Implementation Research to identify barriers and select implementation strategies. Using mix-methods research, including surveys and informal discussions, we evaluated current practice, barriers, outcomes, and the sustainability of high-intensity gait training in practice.

Results:
A multicomponent implementation plan that targeted barriers was developed. Before implementation, clinicians reported providing several balance, strength training, and gait interventions to improve walking. Barriers to using high-intensity gait training included knowledge, beliefs, adaptability of high-intensity gait training, resources, culture, and others. Twenty-six implementation strategies were selected to target the barriers. Surveys and informal discussions identified significant changes in perceived practice, adoption of high-intensity gait training, and positive impacts on the health system. The 2-year follow-up survey indicated that the new practice was sustained.

Discussion and Conclusions:
Using a multicomponent implementation plan that targeted barriers, we successfully implemented high-intensity gait training in clinical practice. Contributors to successful implementation may include the implementation methods, usual care interventions, and clinicians' readiness for this change.

Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A352.)
Temporal But Not Spatial Gait Parameters Associated With Lower Balance Capacity in Moderate-High Functioning Persons With Stroke
Authors: Handelzalts Shirley , Steinberg-Henn Flavia , Farquhar Jenna , Shkedy Rabani Anat , Levy Sigal , Riemer Raziel , Soroker Nachum , Melzer Itshak 
Published: August 2021

Background and purpose:
Falls are a major health concern after stroke. Spatial and temporal gait asymmetry and variability can contribute to instability and increased fall risk in persons with stroke (PwS). We aimed to quantify gait spatiotemporal symmetry and variability parameters in PwS undergoing rehabilitation in the subacute stage of the disease, by comparison to healthy participants, and to examine the associations between these parameters and patients' reactive and proactive balance capacity.

Methods:
Twenty-two PwS and 12 healthy adults walked over a computerized treadmill system at their self-selected walking speed. Symmetry and variability of gait parameters (step length, swing time, and stance time) as well as upper extremity and lower extremity angular range of motion in the sagittal plane were extracted. In addition, the Berg Balance Scale (BBS) and the fall threshold in response to sudden surface translations at increasing intensities were assessed.

Results:
PwS demonstrated significantly higher asymmetry in all gait parameters in comparison to controls. Also, PwS demonstrated increased stance time variability in comparison to healthy controls and increased swing time variability in the paretic lower extremity. Significant negative associations were found between fall threshold and stance time asymmetry in PwS (r = −0.48, P = 0.022), between the BBS and swing time asymmetry (r = −0.50, P = 0.018), and between the BBS and stance time variability of the paretic lower extremity (r = −0.56, P = 0.006).

Discussion and Conclusions:
Findings highlight the importance of gait temporal symmetry and variability measures for dynamic balance control after stroke. These parameters should be considered when assessing gait recovery and safety in PwS.

Video Abstract available for more insight from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A355).
Brief Report: Vaginal Viral Shedding With Undetectable Plasma HIV Viral Load in Pregnant Women Receiving 2 Different Antiretroviral Regimens: A Randomized Clinical Trial
Authors: Frenkel Lisa M. , Morrison R. Leavitt , Fuller Trevon L. , Gouvêa Maria Isabel , Benamor Teixeira Maria de Lourdes , Coombs Robert W. , Shapiro David E. , Mirochnick Mark , Hennessey Roslyn , Whitson Kyle , Chakhtoura Nahida , João Esaú C. 
Published: August 2021

Background:
Pregnant women using antiretrovirals (ARVs) may have persistent vaginal viral shedding, which could be associated with sexual and perinatal HIV transmission. However, there are scant data on vaginal viral load (VVL) in pregnant women with undetectable plasma viral load (PVL).

Methods:
This study was a post hoc analysis of an open-label randomized trial to evaluate the virologic response of 2 ART regimens. The participants were ART-naive women living with HIV initiating ART regimens between 20 and 36 weeks of pregnancy recruited at 19 clinical sites in 6 countries. Participants were randomized to receive 400 mg of raltegravir 2 times a day or 600 mg of efavirenz 4 times a day in addition to 150 mg of lamivudine and 300 mg of zidovudine 2 times a day. VVL and PVL tests were performed at every study visit. The primary outcome measures were HIV-1 PVL and VVL at maternal study week 4 and rates of perinatal HIV transmission.

Results:
A total of 408 were enrolled, of whom 323 had VVL samples 4 weeks after enrollment and were included in this analysis. Among women with undetectable/nonquantifiable PVL during ART, the overall rate of quantifiable VVL at week 4 was 2.54% (7/275). Of the 275 with nonquantifiable PVL, 99.1% (115/116) and 96.2% (153/159) had nonquantifiable VVL in the efavirenz and raltegravir arms, respectively. None of the 7 women with quantifiable VVL at the week 4 study visit transmitted HIV to their infants.

Conclusions:
Detectable VVL in pregnant women with undetectable/nonquantifiable PVL while receiving ART was rare and not associated with perinatal HIV transmission.
Lumbar Puncture for Diagnosis of Idiopathic Intracranial Hypertension in Typical Patients
Authors: Margolis Mathew S. , DeBusk Adam A. , Moster Mark L. , Falardeau Julie M. , Eggenberger Eric R. , Sergott Robert C. , Van Stavern Gregory P. 
Published: August 2021

Background:
Patients with typical features of pseudotumor cerebri syndrome (PTCS) must undergo lumbar puncture (LP) to demonstrate elevated opening pressure and cerebrospinal fluid (CSF) analysis to rule out alternative diagnoses. As LP may be associated with significant morbidity, this study aims to determine its necessity in diagnosing typical PTCS.

Methods:
Retrospective chart review at 3 university-based neuro-ophthalmology practices included women aged 18–45 years with body mass index >25, papilledema, negative neuroimaging, and who met criteria for PTCS or probable PTCS.

Results:
One hundred fifty-six patients were enrolled. Seven (4.5%) had clinically insignificant CSF abnormalities. No diagnoses or management changed based on LP/CSF results.

Conclusion:
LP may not be routinely required in the initial evaluation of typical patients with PTCS evaluated by experienced clinicians We caution, however, that further prospective study is required to determine potential risks and benefits of LP as a tool in the diagnosis of IIH before recommending general practice changes.
Involvement of Ocular Muscles in Patients With Myasthenia Gravis With Nonocular Onset
Authors: Lei Lin , Fan Zhirong , Su Shengyao , Xu Min , Chen Hai , Zhu Wenjia , Luan Qinrong , Da Yuwei 
Published: August 2021

Background:
Myasthenia gravis (MG) is an autoimmune disorder involving neuromuscular junctions and more than half of MG patients manifested with extraocular muscle weakness initially. In the remained patients, ocular weakness may occur later in the course of the disease. However, little data are available about ocular involvement in such patients. Therefore, the study aims to investigate ocular weakness in MG patients with nonocular onset and evaluate the associated factors influencing it.

Methods:
In our monocentric retrospective study, 54 adult-onset patients with MG with nonocular onset were included and were followed up for at least 2 years from the onset. The primary outcome was the occurrence of ptosis, diplopia, or both. Kaplan–Meier analysis was performed to estimate the time to the ocular weakness, and log-rank tests were used to analyze the association between clinical characteristics and ocular weakness. Multivariate Cox proportional hazards regression models were used to identify factors associated with ocular involvement.

Results:
A total of 47 (87.0%) patients developed ocular weakness during the study period. The median time to ocular weakness was 6.0 months. Time to the ocular involvement was earlier in patients with bulbar onset (P = 0.007), whereas patients receiving pyridostigmine monotherapy and immunomodulatory therapy had a longer median time of ocular weakness (P < 0.0001). No significant difference was noted between ocular weakness and age of onset, gender, and thymoma. The Cox analysis showed that bulbar onset was a risk factor of ocular weakness (adjusted hazard ratio [HR] 2.65, 95% confidence interval [CI] 1.41–4.99), whereas pyridostigmine monotherapy (adjusted HR 0.28, 95% CI 0.13–0.60) and immunotherapy (adjusted HR 0.09, 95% CI 0.04–0.22) were protective factors.

Conclusions:
Eighty-seven percent of patients with MG with nonocular onset developed ocular weakness. Bulbar onset was an independent risk factor for ocular involvement, whereas pyridostigmine and immunotherapy were protective factors.
Interictal Spikes as an EEG Biomarker of Cognitive Impairment
Authors: Holmes Gregory L. 
Published: August 2021

Summary:Although interictal spikes (IISs) are a well-established EEG biomarker for epilepsy, whether they are also a biomarker of cognitive deficits is unclear. Interictal spikes are dynamic events consisting of a synchronous discharge of neurons producing high frequency oscillations and a succession of action potentials which disrupt the ongoing neural activity. There are robust data showing that IISs result in transitory cognitive impairment with the type of deficit specific to the cognitive task and anatomic location of the IIS. Interictal spike, particularly if frequent and widespread, can impair cognitive abilities, through interference with waking learning and memory and memory consolidation during sleep. Interictal spikes seem to be particularly concerning in the developing brain where animal data suggest that IISs can lead to adverse cognitive effects even after the disappearance of the spikes. Whether a similar phenomenon occurs in human beings is unclear. Thus, although IISs are a clear biomarker of transitory cognitive impairment, currently, they lack sensitivity and specificity as a biomarker for enduring cognitive impairment.
Neurobehavioral Biomarkers: An EEG Family Reunion
Authors: Ewen Joshua B. , Levin April R. 
Published: August 2021

Summary:
The field of clinical EEG has had an uneasy relationship with the use of this technology for clinical cognitive applications and often for good reason. However, apart from its clinical use, EEG has had a tradition as a major tool in cognitive psychology and cognitive neuroscience dating back at least to the 1960s. Based on accumulated knowledge from its research application, EEG-based biomarkers are beginning to see applications in clinical trials and may eventually enter clinical care. We address concerns surrounding quality control, the treatment of artifact, and normal variants and how developments in engineering, biomarker validation, and implementation science rigorously applied to these tools can lead to well-justified approaches.
Metabolomic and Inflammatory Signatures of Symptom Dimensions in Major Depression
Authors: Brydges Christopher R , Bhattacharyya Sudeepa , Dehkordi Siamak Mahmoudian , Milaneschi Yuri , Penninx Brenda , Jansen Rick , Kristal Bruce S. , Han Xianlin , Arnold Matthias , Kastenmüller Gabi , Bekhbat Mandakh , Mayberg Helen S , Craighead W Edward , Rush A John , Fiehn Oliver , Dunlop Boadie W , Kaddurah-Daouk Rima ,   Mood Disorders Precision Medicine Consortium
Published: August 2021

ABSTRACTBackgroundMajor depressive disorder (MDD) is a highly heterogenous disease, both in terms of clinical profiles and pathobiological alterations. Recently, immunometabolic dysregulations were shown to be correlated with atypical, energy-related symptoms but less so with the Melancholic or Anxious distress symptom dimensions of depression in The Netherlands Study of Depression and Anxiety (NESDA) study. In this study, we aimed to replicate these immunometabolic associations and to characterize the metabolomic correlates of each of the three MDD dimensions.MethodsUsing three clinical rating scales, Melancholic, and Anxious distress, and Immunometabolic (IMD) dimensions were characterized in 158 patients who participated in the Predictors of Remission to Individual and Combined Treatments (PReDICT) study and from whom plasma and serum samples were available. The NESDA-defined inflammatory index, a composite measure of interleukin-6 and C-reactive protein, was measured from pre-treatment plasma samples and a metabolomic profile was defined using serum samples analyzed on three metabolomics platforms targeting fatty acids and complex lipids, amino acids, acylcarnitines, and gut microbiome-derived metabolites among other metabolites of central metabolism.ResultsThe IMD clinical dimension and the inflammatory index were positively correlated (r=0.19, p=.019) after controlling for age, sex, and body mass index, whereas the Melancholic and Anxious distress dimensions were not, replicating the previous NESDA findings. The three symptom dimensions had distinct metabolomic signatures using both univariate and set enrichment statistics. IMD severity correlated mainly with gut-derived metabolites and a few acylcarnitines and long chain saturated free fatty acids. Melancholia severity was significantly correlated with several phosphatidylcholines, primarily the ether-linked variety, lysophosphatidylcholines, as well as several amino acids. Anxious distress severity correlated with several medium and long chain free fatty acids, both saturated and polyunsaturated ones, sphingomyelins, as well as several amino acids and bile acids.ConclusionThe IMD dimension of depression is reliably associated with markers of inflammation. Metabolomics provides powerful tools to inform about depression heterogeneity and molecular mechanisms related to clinical dimensions in MDD, which include a link to gut microbiome and lipids implicated in membrane structure and function.
Immune and metabolic beneficial effects of Beta 1,3-1,6 glucans produced by two novel strains of Aureobasidium pullulans in healthy middle-aged Japanese men: An exploratory study
Authors: Ikewaki Nobunao , Sonoda Tohru , Kurosawa Gene , Iwasaki Masaru , Dedeepiya Vidyasagar Devaprasad , Senthilkumar Rajappa , Preethy Senthilkumar , Abraham Samuel JK 
Published: August 2021

AbstractBackgroundImbalances in glucose and lipid metabolism in the background of a declining immune system, along with aging, make one prone to glucolipotoxicity-related diseases such as hepatic steatosis and to high risk of infection-related mortality, as with COVID-19, warranting a safe prophylactic measure to help regulate both metabolism and the immune system. Based on the beneficial effects of the AFO-202 strain of black yeast Aureobasidium pullulans-produced beta 1,3-1,6 glucan in balancing of blood glucose and immune enhancement, and that of the N-163 strain of the same species in lipid metabolism and immune modulation, in this pilot study, we have evaluated their specific benefits in healthy human subjects.MethodsSixteen healthy Japanese male volunteers (aged 40 to 60 years) took part in this clinical trial. They were divided into four groups (n = 4 each): Group I consumed AFO-202 beta glucan (2 sachets of 1 g each per day), IA for 35 days and IB for 21 days; Group II consumed a combination of AFO-202 beta glucan (2 sachets of 1 g each) and N-163 beta glucan (1 sachet of 15 g gel each per day), IIA for 35 days and IIB for 21 days. Investigations for immune stimulation, anti-glycaemic, and anti-cholesterolemia biomarkers were undertaken in all four groups.ResultsIn terms of metabolic control of glucose, the decrease in HbA1C and glycated albumin (GA) was significantly better in Group I compared with the other groups. Immune enhancement in terms of a significant increase of eosinophils and monocytes and marginal decrease in D-dimer levels, decrease in neutrophil-to-lymphocyte ratio (NLR), with an increase in the lymphocyte-to-CRP ratio (LCR) and leukocyte-to-CRP ratio (LeCR) was observed in Group I. Regulation of lipids by decrease in total and LDL cholesterol was better in Group II, and immunomodulation of coagulation-associated and anti-inflammatory markers by a decrease of CD11b, serum ferritin, galectin-3, fibrinogen was profound in Group II.ConclusionA. pullulans, a polythermotolerant black yeast - produced AFO-202 beta glucan has balanced blood glucose with marginal immune enhancement in healthy individuals, which when combined with N-163 beta glucan, balanced the lipid profile and immunomodulation. This outcome warrants larger clinical trials to understand the mechanisms and explore the potentials of these safe food supplements in prevention and prophylaxis of diseases due to dysregulated glucose and lipid metabolism, such as fatty liver disease, and infections such as COVID-19 in which a balanced immune activation and immunomodulation are of utmost importance, besides their administration as an adjunct to existing therapeutic approaches of both communicable and non-communicable diseases.
Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention deficit hyperactivity disorder
Authors: Rajagopal Veera M. , Duan Jinjie , Vilar-Ribó Laura , Grove Jakob , Zayats Tetyana , Ramos-Quiroga J. Antoni , Satterstrom F. Kyle , Soler Artigas María , Bybjerg-Grauholm Jonas , Bækvad-Hansen Marie , Als Thomas D. , Rosengren Anders , Daly Mark J. , Neale Benjamin M. , Nordentoft Merete , Werge Thomas , Mors Ole , Hougaard David M. , Mortensen Preben B. , Ribasés Marta , Børglum Anders D. , Demontis Ditte 
Published: August 2021

ABSTRACTAttention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder, with onset in childhood (“childhood ADHD”), and around two thirds of affected individuals will continue to have ADHD symptoms in adulthood (“persistent ADHD”). Age at first diagnosis can vary, and sometimes ADHD is first diagnosed in adulthood (“late-diagnosed ADHD”).In this study, we analyzed a large Danish population-based case-cohort generated by iPSYCH in order to identify common genetic risk loci and perform in-depth characterization of the polygenic architecture of childhood (N=14,878), persistent (N=1,473) and late-diagnosed ADHD (N=6,961) alongside 38,303 controls. Additionally, the burden of rare protein truncating variants in the three groups were evaluated in whole-exome sequencing data from a subset of the individuals (7,650 ADHD cases and 8,649 controls). We identified genome-wide significant loci associated with childhood ADHD (four loci) and late-diagnosed ADHD (one locus). In analyses of the polygenic architecture, we found higher polygenic score (PGS) of ADHD risk variants in persistent ADHD (mean PGS=0.41) compared to childhood (mean PGS=0.26) and late-diagnosed ADHD (mean PGS=0.27), and we found a significant decreased genetic correlation of late-diagnosed ADHD with inattention (rg=0.57) compared to childhood ADHD (rg=0.86). These results suggest that a higher ADHD polygenic risk burden is associated with persistence of symptoms, and that a later diagnosis of ADHD could be due in part to genetic factors. Additionally, childhood ADHD demonstrated both a significantly increased genetic overlap with autism compared to late-diagnosed ADHD as well as the highest burden of rare protein-truncating variants in highly constrained genes among ADHD subgroups (compared to controls: beta=0.13, P=2.41×10−11). Late-diagnosed ADHD demonstrated significantly larger genetic overlap with depression than childhood ADHD and no increased burden in rare protein-truncating variants (compared to controls: beta=0.06). Overall, our study finds genetic heterogeneity among ADHD subgroups and suggests that genetic factors influence time of first ADHD diagnosis, persistence of ADHD and comorbidity patterns in the sub-groups.
Antibody Attributes that Predict the Neutralization and Effector Function of Polyclonal Responses to SARS-CoV-2
Authors: Natarajan Harini , Xu Shiwei , Crowley Andrew R. , Butler Savannah E. , Weiner Joshua A. , Bloch Evan M. , Littlefield Kirsten , Benner Sarah E. , Shrestha Ruchee , Ajayi Olivia , Wieland-Alter Wendy , Sullivan David , Shoham Shmuel , Quinn Thomas C. , Casadevall Arturo , Pekosz Andrew , Redd Andrew D. , Tobian Aaron A.R. , Connor Ruth I. , Wright Peter F. , Ackerman Margaret E. 
Published: August 2021

AbstractWhile antibodies provide significant protection from SARS-CoV-2 infection and disease sequelae, the specific attributes of the humoral response that contribute to immunity are incompletely defined. In this study, we employ machine learning to relate characteristics of the polyclonal antibody response raised by natural infection to diverse antibody effector functions and neutralization potency with the goal of generating both accurate predictions of each activity based on antibody response profiles as well as insights into antibody mechanisms of action. To this end, antibody-mediated phagocytosis, cytotoxicity, complement deposition, and neutralization were accurately predicted from biophysical antibody profiles in both discovery and validation cohorts. These predictive models identified SARS-CoV-2-specific IgM as a key predictor of neutralization activity whose mechanistic relevance was supported experimentally by depletion. Validated models of how different aspects of the humoral response relate to antiviral antibody activities suggest desirable attributes to recapitulate by vaccination or other antibody-based interventions.