bluuebunny/crossref_metadata_2025 huggingface dataset:
NRXN1α+/- is associated with increased excitability in ASD iPSC-derived neurons
Authors: Avazzadeh Sahar , Quinlan Leo R. , Reilly Jamie , McDonagh Katya , Jalali Amirhossein , Wang Yanqin , McInerney Veronica , Krawczyk Janusz , Ding Yicheng , Fitzgerald Jacqueline , O’Sullivan Matthew , Forman Eva B. , Lynch Sally A. , Ennis Sean , Feerick Niamh , Reilly Richard , Li Weidong , Shen Xu , Yang Guangming , Lu Yin , Peeters Hilde , Dockery Peter , O’Brien Timothy , Shen Sanbing , Gallagher Louise
Published: September 2021

Background

NRXN1 deletions are identified as one of major rare risk factors for autism spectrum disorder (ASD) and other neurodevelopmental disorders. ASD has 30% co-morbidity with epilepsy, and the latter is associated with excessive neuronal firing. NRXN1 encodes hundreds of presynaptic neuro-adhesion proteins categorized as NRXN1α/β/γ. Previous studies on cultured cells show that the short NRXN1β primarily exerts excitation effect, whereas the long NRXN1α which is more commonly deleted in patients involves in both excitation and inhibition. However, patient-derived models are essential for understanding functional consequences of NRXN1α deletions in human neurons. We recently derived induced pluripotent stem cells (iPSCs) from five controls and three ASD patients carrying NRXN1α+/- and showed increased calcium transients in patient neurons.

Methods

In this study we investigated the electrophysiological properties of iPSC-derived cortical neurons in control and ASD patients carrying NRXN1α+/- using patch clamping. Whole genome RNA sequencing was carried out to further understand the potential underlying molecular mechanism.

Results

NRXN1α﻿﻿+﻿﻿/﻿﻿- cortical neurons were shown to display larger sodium currents, higher AP amplitude and accelerated depolarization time. RNASeq analyses revealed transcriptomic changes with significant upregulation glutamatergic synapse and ion channels/transporter activity including voltage-gated potassium channels (GRIN1, GRIN3B, SLC17A6, CACNG3, CACNA1A, SHANK1), which are likely to couple with the increased excitability in NRXN1α﻿﻿+﻿﻿/﻿﻿- cortical neurons.

Conclusions

Together with recent evidence of increased calcium transients, our results showed that human NRXN1α﻿﻿+﻿﻿/﻿﻿- isoform deletions altered neuronal excitability and non-synaptic function, and NRXN1α﻿﻿+﻿﻿/﻿﻿- patient iPSCs may be used as an ASD model for therapeutic development with calcium transients and excitability as readouts.
Towards cross-Canada monitoring of the unregulated street drug supply
Authors: Biggar Emily , Papamihali Kristi , Leclerc Pascale , Hyshka Elaine , Graham Brittany , Taylor Marliss , Payer Doris , Maloney-Hall Bridget , Buxton Jane A.
Published: September 2021

Background

The well-being of people who use drugs (PWUD) continues to be threatened by substances of unknown type or quantity in the unregulated street drug supply. Current efforts to monitor the drug supply are limited in population reach and comparability. This restricts capacity to identify and develop measures that safeguard the health of PWUD. This study describes the development of a low-barrier system for monitoring the contents of drugs in the unregulated street supply. Early results for pilot sites are presented and compared across regions.

Methods

The drug content monitoring system integrates a low-barrier survey and broad spectrum urine toxicology screening to compare substances expected to be consumed and those actually in the drug supply. The system prototype was developed by harm reduction pilot projects in British Columbia (BC) and Montreal with participation of PWUD. Data were collected from harm reduction supply distribution site clients in BC, Edmonton and Montreal between May 2018–March 2019. Survey and urine toxicology data were linked via anonymous codes and analyzed descriptively by region for trends in self-reported and detected use.

Results

The sample consisted of 878 participants from 40 sites across 3 regions. Reported use of substances, their detection, and concordance between the two varied across regions. Methamphetamine use was reported and detected most frequently in BC (reported: 62.8%; detected: 72.2%) and Edmonton (58.3%; 68.8%). In Montreal, high concordance was also observed between reported (74.5%) and detected (86.5%) cocaine/crack use. Among those with fentanyl detected, the percentage of participants who used fentanyl unintentionally ranged from 36.1% in BC, 78.6% in Edmonton and 90.9% in Montreal.

Conclusions

This study is the first to describe a feasible, scalable monitoring system for the unregulated drug supply that can contrast expected and actual drug use and compare trends across regions. The system used principles of flexibility, capacity-building and community participation in its design. Results are well-suited to meet the needs of PWUD and inform the local harm reduction services they rely on. Further standardization of the survey tool and knowledge mobilization is needed to expand the system to new jurisdictions.
Functional outcomes and quality of life after surgical treatment of spinopelvic dissociation: a case series with one-year follow-up
Authors: Petryla Giedrius , Bobina Rokas , Uvarovas Valentinas , Kurtinaitis Jaunius , Sveikata Tomas , Ryliškis Sigitas , Kvederas Giedrius , Šatkauskas Igoris
Published: September 2021

Background

Spinopelvic dissociation is a transverse sacral fracture in conjunction with a vertical fracture of the sacrum on both sides, which causes the dissociation of the upper sacrum and spine from the pelvis. The most common causes of these fractures are high energy injuries such as falls from height or motor vehicle accidents. Spinopelvic dissociation is rare and heterogenous with severe associated injuries. The aim of this study was to assess the injury characteristics, changes in the quality of life and functional outcomes in the 1-year period after spinopelvic dissociation.

Materials and methods

During the period of 4 years (January 2016 and January 2020), 17 patients with spinopelvic dissociation were admitted to our centre and included in this single-centre prospective cohort study. One patient died during the admission; therefore 16 patients were enrolled in the analysis. Patients were followed-up for 12 months. The quality of life changes were evaluated via the SF-36 questionnaire, and the functional outcomes were evaluated using the Majeed pelvic score. Patients completed their questionnaires twice: firstly during hospitalization (regarding their pre-traumatic condition); and once again 1 year after their injury (regarding their current condition).

Results

The mean age of the patients was 40.2 ± 17.7 years. Mean Majeed, PCS and MCS scores of SF-36 before the injury were 95.81 ± 9.50, 55.87 ± 8.89, and 43.76 ± 12.45, respectively. Mean Majeed, PCS and MCS scores 1 year after the injury were 71.13 ± 20.98, 43.45 ± 9.64, and 43.41 ± 7.56. During the period of 1 year after the injury, Majeed and PCS results reduced statistically significantly (P = 0.001 andP = 0.003, respectively), while MCS results remained similar (P = 0.501).

Conclusions

According to the data of our study, for patients with spinopelvic dissociation functional outcomes are significantly reduced and only one-third of the patients achieved pre-traumatic functional outcomes 1 year after the injury.
Validity and reliability of new instruments for measuring patient satisfaction with removable dentures, Arabic Version
Authors: Al Jaghsi Ahmad , Saeed Musab , Abu Fanas Salem , Alqutaibi Ahmed Yaseen , Mundt Torsten
Published: September 2021

Background

The psychometric properties of self-administered instruments for measuring patient satisfaction with removable dentures should be tested before inviting patients to express their opinions. This study aimed to evaluate the validity and reliability of new instruments in the Arabic language that measure patient satisfaction with all types of removable dentures.

Methods

A three-step methodology was used to translate and test the instruments. In step one, the instruments were translated from tested German instruments to develop the pilot questionnaires. In step two, the face validity of the pilot questionnaires was tested through three rounds of interviews. There were 15, 13, and 15 participants per round, respectively. At the end of every round, the results of the interviews were discussed with an expert panel. The expert panel confirmed the form and the type of questionnaires’ adjustments before a new round of interviews began. At the end of step two, the final form of the questionnaires was reached. In step three, 235 questionnaires were distributed to 133 participants to estimate the construct validity of the upper jaw and the lower jaw questionnaires. After one week, the participants were asked to complete the questionnaires again. A total of 102 questionnaires were returned and used to assess the instruments’ reliability. Factor analysis was used to assess the construct validity. The intraclass correlation coefficient and Cronbach’s alpha were used to estimate the reliability and suitability of the items in the indexes.

Results

The result of step one was two pilot questionnaires. The pilot questionnaires were adjusted in step two. At the end of step two, the questionnaires proved to have good face validity. Factor analyses in step three revealed that only one factor could be retained. The one-factor model explained 60.95% and 63.06 of the total variance of the upper jaw and lower jaw questionnaires, respectively. The items in every questionnaire shared the same cluster and could be summed to form an upper jaw index and lower jaw index that reflected patient satisfaction with removable dentures. Cronbach’s alpha values indicated excellent internal consistency and reliability for the upper jaw questionnaire (α = 0.91) and the lower jaw questionnaire (α = 0.92). Intraclass correlation coefficient values ranged from 0.72 to 0.95, which can be considered “moderate” to “excellent”.

Conclusions

The Arabic version of questionnaires and indexes assessing patient satisfaction with upper and lower removable dentures are reliable and valid self-administered instruments.
Factors associated with access to assistive technology and telecare in home-dwelling people with dementia: baseline data from the LIVE@Home.Path trial
Authors: Puaschitz Nathalie Genevieve , Jacobsen Frode Fadnes , Mannseth Janne , Angeles Renira Corinne , Berge Line Iden , Gedde Marie Hidle , Husebo Bettina Sandgathe
Published: September 2021

Background

There is a knowledge gap regarding factors that may influence the access to different devices for home-dwelling people with dementia (PwD). The aim of this study was to identify different assistive technology and telecare (ATT) devices installed in the home and key factors associated with access to such technology.

Methods

The baseline data came from the LIVE@Home.Path trial, a 24-month multi-component intervention including PwDs and their informal caregivers (dyads) and were collected through semi-quantitative questionnaires in three Norwegian municipalities between May and November of 2019. Regression models were applied to detect demographic and clinical factors associated with access to ATT.

Results

Of 438 screened dyads, 276 were included at baseline. The mean ages of the PwDs and caregivers were 82 ± 7.0 and 66 ± 12 years, respectively, and 62.8% of the PwD were female and 73.5% had access to any type of ATT. The majority had traditional equipment such as stove guards (43.3%) and social alarms (39.5%) or everyday technology, e.g. calendar support and door locks (45.3%). Multivariate regression analyses revealed that access to a social alarm was more often available for females than males, at increased age, and when the PwD lived alone, while tracking devices (14.9%) were more often accessible at lower age. Everyday technology was more often available for females, at increased age of the PwD and the caregiver, higher comorbidity, and poor IADL (instrumental activities of daily living) function. For PwDs with severe dementia, access to ATT was significantly associated with poor IADL function, having their children as the main caregiver (61.3%), and having caregivers who contributed 81–100% to their care (49.5%).

Conclusions

Home-dwelling PwDs mainly had access to traditional and obligated devices, followed by everyday technology. There is unmet potential for communication, tracking, and sensing technology, especially for devices not offered by the municipalities. Gender, ages of the PwD and caregiver, cohabitation status, and physical function were the main associated factors for access to ATT.

Trial registration: ClinicalTrials.gov NCT04043364.
The views of public service managers on the implementation of National Health Insurance in primary care: a case of Johannesburg Health District, Gauteng Province, Republic of South Africa
Authors: Murphy S D , Moosa S
Published: September 2021

Background

The South African government is implementing National Health Insurance (NHI) as a monopsony health care financing mechanism to drive the country towards Universal Health Coverage (UHC). Strategic purchasing, with separation of funder, purchaser and provider, underpins this initiative. The NHI plans Contracting Units for Primary healthcare (PHC) Services (CUPS) to function as either independent sub-district purchasers or public providers and District Health Management Offices (DHMOs) to support and monitor these CUPS. This decentralised operational unit of PHC, the heartbeat of NHI, is critical to the success of NHI. The views of district-level managers, who are responsible for these units, are fundamental to this NHI implementation. This qualitative study aimed to explore district and sub-district managerial views on NHI and their role in its implementation.

Methods

Purposive sampling was used to identify key respondents from a major urban district in Gauteng, South Africa, for participation in in-depth interviews. This study used framework analysis methodology within MaxQDA software.

Results

Three main themes were identified: managerial engagement in NHI policy development (with two sub-themes), managerial views on NHI (with three sub-themes) and perceptions of current NHI implementation (with six sub-themes). The managers viewed NHI as a social and moral imperative but lacked clarity and insight into the NHI Bill as well as the associated implementation strategies. The majority of respondents had not had the opportunity to engage in NHI policy formulation. Managers cited several pitfalls in current organisational operations. The respondents felt that national and provincial governments continue to function in a detached and rigid top-down hierarchy. Managers highlighted the need for their inclusion in NHI policy formulation and training and development for them to oversee the implementation strategies.

Conclusions

It appears that strategic purchasing is not being operationalised in PHC. NHI policy implementation appears to function in a rigid top-down hierarchy that excludes key stakeholders in the NHI implementation strategy. The findings of this study suggest an inadequate decentralisation of healthcare governance within the public sector necessary to attain UHC. District managers need to be engaged and capacitated to operationalise the planned decentralised purchasing-provision function of the DHS within the NHI Bill.
Circular RNAs’ cap-independent translation protein and its roles in carcinomas
Authors: He Lian , Man Changfeng , Xiang Shouyan , Yao Lin , Wang Xiaoyan , Fan Yu
Published: September 2021

Circular RNAs a kind of covalently closed RNA and widely expressed in eukaryotes. CircRNAs are involved in a variety of physiological and pathological processes, but their regulatory mechanisms are not fully understood. Given the development of the RNA deep-sequencing technology and the improvement of algorithms, some CircRNAs are discovered to encode proteins through the cap-independent mechanism and participate in the important process of tumorigenesis and development. Based on an overview of CircRNAs, this paper summarizes its translation mechanism and research methods, and reviews the research progress of CircRNAs translation in the field of oncology in recent years. Moreover, this paper aims to provide new ideas for tumor diagnosis and treatment through CircRNAs translation.
Sex difference in the interrelationship between TNF-α and oxidative stress status in first-episode drug-naïve schizophrenia
Authors: Zhu Minghuan , Liu Zhenjing , Guo Yanhong , Sultana Mst. Sadia , Wu Kang , Lang Xiaoe , Lv Qinyu , Huang Xiao , Yi Zhenghui , Li Zezhi
Published: September 2021

Background

Increasing evidence indicates that dysregulated TNF-α and oxidative stress (OxS) contribute to the pathophysiology of schizophrenia. Additionally, previous evidence has demonstrated sex differences in many aspects of schizophrenia including clinical characteristics, cytokines, and OxS markers. However, to the best of our knowledge, there is no study investigating sex differences in the association between TNF-α, the OxS system, and their interaction with clinical symptoms in schizophrenia patients, especially in first-episode drug-naïve (FEDN) patients.

Methods

A total of 119 FEDN schizophrenia patients and 135 healthy controls were recruited for this study. Serum TNF-α, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) were measured. The Positive and Negative Syndrome Scale (PANSS) was applied to evaluate psychotic symptoms. Two-way ANOVA, partial correlation analysis, and multivariate regression analysis were performed.

Results

A sex difference in MDA levels was demonstrated only in healthy controls (F = 7.06, pBonferroni = 0.045) and not seen in patients. Furthermore, only male patients had higher MDA levels than male controls (F = 8.19, pBonferroni = 0.03). Additionally, sex differences were observed in the association of TNF-α and MDA levels with psychotic symptoms (all pBonferroni < 0.05). The interaction of TNF-α and MDA was only associated with general psychopathology symptom in male patients (B = − 0.07, p = 0.02).

Conclusion

Our results demonstrate the sex difference in the relationship between TNF-α, MDA, and their interaction with psychopathological symptoms of patients with schizophrenia.
Home-based self-help telerehabilitation of the upper limb assisted by an electromyography-driven wrist/hand exoneuromusculoskeleton after stroke
Authors: Nam Chingyi , Zhang Bingbing , Chow Tszying , Ye Fuqiang , Huang Yanhuan , Guo Ziqi , Li Waiming , Rong Wei , Hu Xiaoling , Poon Waisang
Published: September 2021

Background

Most stroke survivors have sustained upper limb impairment in their distal joints. An electromyography (EMG)-driven wrist/hand exoneuromusculoskeleton (WH-ENMS) was developed previously. The present study investigated the feasibility of a home-based self-help telerehabilitation program assisted by the aforementioned EMG-driven WH-ENMS and its rehabilitation effects after stroke.

Methods

Persons with chronic stroke (n = 11) were recruited in a single-group trial. The training progress, including the training frequency and duration, was telemonitored. The clinical outcomes were evaluated using the Fugl–Meyer Assessment (FMA), Action Research Arm Test (ARAT), Wolf Motor Function Test (WMFT), Motor Functional Independence Measure (FIM), and Modified Ashworth Scale (MAS). Improvement in muscle coordination was investigated in terms of the EMG activation level and the Co-contraction Index (CI) of the target muscles, including the abductor pollicis brevis (APB), flexor carpi radialis-flexor digitorum (FCR-FD), extensor carpi ulnaris-extensor digitorum (ECU-ED), biceps brachii (BIC), and triceps brachii (TRI). The movement smoothness and compensatory trunk movement were evaluated in terms of the following two kinematic parameters: number of movement units (NMUs) and maximal trunk displacement (MTD). The above evaluations were conducted before and after the training.

Results

All of the participants completed the home-based program with an intensity of 63.0 ± 1.90 (mean ± SD) min/session and 3.73 ± 0.75 (mean ± SD) sessions/week. After the training, motor improvements in the entire upper limb were found, as indicated by the significant improvements (P < 0.05) in the FMA, ARAT, WMFT, and MAS; significant decreases (P < 0.05) in the EMG activation levels of the APB and FCR-FD; significant decreases (P < 0.05) in the CI of the ECU–ED/FCR–FD, ECU–ED/BIC, FCR–FD/APB, FCR–FD/BIC, FCR–FD/TRI, APB/BIC and BIC/TRI muscle pairs; and significant reductions (P < 0.05) in the NMUs and MTD.

Conclusions

The results suggested that the home-based self-help telerehabilitation program assisted by EMG-driven WH-ENMS is feasible and effective for improving the motor function of the paretic upper limb after stroke.

Trial registrationClinicalTrials.gov. NCT03752775; Date of registration: November 20, 2018.
Concurrent validity of human pose tracking in video for measuring gait parameters in older adults: a preliminary analysis with multiple trackers, viewing angles, and walking directions
Authors: Mehdizadeh Sina , Nabavi Hoda , Sabo Andrea , Arora Twinkle , Iaboni Andrea , Taati Babak
Published: September 2021

Background

Many of the available gait monitoring technologies are expensive, require specialized expertise, are time consuming to use, and are not widely available for clinical use. The advent of video-based pose tracking provides an opportunity for inexpensive automated analysis of human walking in older adults using video cameras. However, there is a need to validate gait parameters calculated by these algorithms against gold standard methods for measuring human gait data in this population.

Methods

We compared quantitative gait variables of 11 older adults (mean age = 85.2) calculated from video recordings using three pose trackers (AlphaPose, OpenPose, Detectron) to those calculated from a 3D motion capture system. We performed comparisons for videos captured by two cameras at two different viewing angles, and viewed from the front or back. We also analyzed the data when including gait variables of individual steps of each participant or each participant’s averaged gait variables.

Results

Our findings revealed that, i) temporal (cadence and step time), but not spatial and variability gait measures (step width, estimated margin of stability, coefficient of variation of step time and width), calculated from the video pose tracking algorithms correlate significantly to that of motion capture system, and ii) there are minimal differences between the two camera heights, and walks viewed from the front or back in terms of correlation of gait variables, and iii) gait variables extracted from AlphaPose and Detectron had the highest agreement while OpenPose had the lowest agreement.

Conclusions

There are important opportunities to evaluate models capable of 3D pose estimation in video data, improve the training of pose-tracking algorithms for older adult and clinical populations, and develop video-based 3D pose trackers specifically optimized for quantitative gait measurement.
Quality of reporting in chiropractic mixed methods research: a methodological review protocol
Authors: Emary Peter C. , Stuber Kent J. , Mbuagbaw Lawrence , Oremus Mark , Nolet Paul S. , Nash Jennifer V. , Bauman Craig A. , Ciraco Carla , Couban Rachel J. , Busse Jason W.
Published: September 2021

Background

Mixed methods designs are increasingly used in health care research to enrich findings. However, little is known about the frequency of use of this methodology in chiropractic research, or the quality of reporting among chiropractic studies using mixed methods.

Objective

To quantify the use and quality of mixed methods in chiropractic research, and explore the association of study characteristics (e.g., authorship, expertise, journal impact factor, country and year of publication) with reporting quality.

Methods

We will conduct a systematic search of MEDLINE, EMBASE, CINAHL, and the Index to Chiropractic Literature to identify all chiropractic mixed methods studies published from inception of each database to December 31, 2020. Articles reporting the use of both qualitative and quantitative methods, or mixed qualitative methods, will be included. Pairs of reviewers will perform article screening, data extraction, risk of bias with the Mixed Methods Appraisal Tool (MMAT), and appraisal of reporting quality using the Good Reporting of A Mixed Methods Study (GRAMMS) guideline. We will explore the correlation between GRAMMS and MMAT scores, and construct generalized estimating equations to explore factors associated with reporting quality.

Discussion

This will be the first methodological review to examine the reporting quality of published mixed methods studies involving chiropractic research. The results of our review will inform opportunities to improve reporting in chiropractic mixed methods studies. Our results will be disseminated in a peer-reviewed publication and presented publicly at conferences and as part of a doctoral thesis.
Systematic analysis of the relationship between ovarian cancer prognosis and alternative splicing
Authors: Zhang Di , Zou Dan , Deng Yue , Yang Lihua
Published: September 2021

Background

Ovarian cancer(OC) is the gynecological tumor with the highest mortality rate, effective biomarkers are of great significance in improving its prognosis. In recent years, there have been many studies on alternative splicing (AS) events, and the role of AS events in tumor has become a focus of attention.

Methods

Data were downloaded from the TCGA database and Univariate Cox regression analysis was performed to determine AS events associated with OC prognosis.Eight prognostic models of OC were constructed in R package, and the accuracy of the models were evaluated by the time-dependent receiver operating characteristic (ROC) curves.Eight types of survival curves were drawn to evaluate the differences between the high and low risk groups.Independent prognostic factors of OC were analyzed by single factor independent analysis and multi-factor independent prognostic analysis.Again, Univariate Cox regression analysis was used to analyze the relationship between splicing factors(SF) and AS events, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis were performed on OS-related SFs to understand the pathways.

Results

Univariate Cox regression analysis showed that among the 15,278 genes, there were 31,286 overall survival (OS) related AS events, among which 1524 AS events were significantly correlated with OS. The area under the time-dependent receiver operating characteristic curve (AUC) of AT and ME were the largest and the RI was the smallest,which were 0.757 and 0.68 respectively. The constructed models have good value for the prognosis assessment of OC patients. Among the eight survival curves, AP was the most significant difference between the high and low risk groups, with a P value of 1.61e − 1.The results of single factor independent analysis and multi-factor independent prognostic analysis showed that risk score calculated by the model and age could be used as independent risk factors.According to univariate COX regression analysis,109 SFs were correlated with AS events and adjusted in two ways: positive and negative.

Conclusions

SFs and AS events can directly or indirectly affect the prognosis of OC patients. It is very important to find effective prognostic markers to improve the survival rate of OC.
Data analysis with Shapley values for automatic subject selection in Alzheimer’s disease data sets using interpretable machine learning
Authors: Bloch Louise , Friedrich Christoph M. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: September 2021

Background

For the recruitment and monitoring of subjects for therapy studies, it is important to predict whether mild cognitive impaired (MCI) subjects will prospectively develop Alzheimer’s disease (AD). Machine learning (ML) is suitable to improve early AD prediction. The etiology of AD is heterogeneous, which leads to high variability in disease patterns. Further variability originates from multicentric study designs, varying acquisition protocols, and errors in the preprocessing of magnetic resonance imaging (MRI) scans. The high variability makes the differentiation between signal and noise difficult and may lead to overfitting. This article examines whether an automatic and fair data valuation method based on Shapley values can identify the most informative subjects to improve ML classification.

Methods

An ML workflow was developed and trained for a subset of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. The validation was executed for an independent ADNI test set and for the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) cohort. The workflow included volumetric MRI feature extraction, feature selection, sample selection using Data Shapley, random forest (RF), and eXtreme Gradient Boosting (XGBoost) for model training as well as Kernel SHapley Additive exPlanations (SHAP) values for model interpretation.

Results

The RF models, which excluded 134 of the 467 training subjects based on their RF Data Shapley values, outperformed the base models that reached a mean accuracy of 62.64% by 5.76% (3.61 percentage points) for the independent ADNI test set. The XGBoost base models reached a mean accuracy of 60.00% for the AIBL data set. The exclusion of those 133 subjects with the smallest RF Data Shapley values could improve the classification accuracy by 2.98% (1.79 percentage points). The cutoff values were calculated using an independent validation set.

Conclusion

The Data Shapley method was able to improve the mean accuracies for the test sets. The most informative subjects were associated with the number of ApolipoproteinE ε4 (ApoE ε4) alleles, cognitive test results, and volumetric MRI measurements.
Shortening time for access to alcohol drives up front-loading behavior, bringing consumption in male rats to the level of females
Authors: Flores-Bonilla Annabelle , De Oliveira Barbara , Silva-Gotay Andrea , Lucier Kyle W. , Richardson Heather N.
Published: September 2021

Background

Incentives to promote drinking (“happy hour”) can encourage faster rates of alcohol consumption, especially in women. Sex differences in drinking dynamics may underlie differential health vulnerabilities relating to alcohol in women versus men. Herein, we used operant procedures to model the happy hour effect and gain insight into the alcohol drinking dynamics of male and female rats.

Methods

Adult male and female Wistar rats underwent operant training to promote voluntary drinking of 10% (w/v) alcohol (8 rats/sex). We tested how drinking patterns changed after manipulating the effort required for alcohol (fixed ratio, FR), as well as the length of time in which rats had access to alcohol (self-administration session length). Rats were tested twice within the 12 h of the dark cycle, first at 2 h (early phase of the dark cycle, “early sessions”) and then again at 10 h into the dark cycle (late phase of the dark cycle, “late sessions”) with an 8-h break between the two sessions in the home cage.

Results

Adult females consumed significantly more alcohol (g/kg) than males in the 30-min sessions with the FR1 schedule of reinforcement when tested late in the dark cycle. Front-loading of alcohol was the primary factor driving higher consumption in females. Changing the schedule of reinforcement from FR1 to FR3 reduced total consumption. Notably, this manipulation had minimal effect on front-loading behavior in females, whereas front-loading behavior was significantly reduced in males when more effort was required to access alcohol. Compressing drinking access to 15 min to model a happy hour drove up front-loading behavior, generating alcohol drinking patterns in males that were similar to patterns in females (faster drinking and higher intake).

Conclusions

This strategy could be useful for exploring sex differences in the neural mechanisms underlying alcohol drinking and related health vulnerabilities. Our findings also highlight the importance of the time of testing for detecting sex differences in drinking behavior.
Identification of different attitudes towards paratuberculosis control using cluster analysis applied on data from an anonymous survey among German cattle farmers
Authors: Zoche-Golob Veit , Pützschel René , Einax Esra , Donat Karsten
Published: September 2021

Background

Paratuberculosis is a common disease in ruminants, causing economic losses in livestock farming, and a relationship between the exposure to its causative agent Mycobacterium avium subsp. paratuberculosis, and Crohn’s disease in humans is discussed. Despite this, only a minority of cattle farmers have enroled in voluntary control programmes in most countries. Therefore, this study aimed at investigating the farmer’s opinion on paratuberculosis and their motivations to participate in a control programme. The objective was to identify different groups among farmers regarding their motivation and thereby contribute to a better understanding of farmers’ attitudes towards paratuberculosis control.

Results

Two hundred twenty-five farmers responded to questionnaires that were distributed among cattle farmers in Saxony and Thuringia, federal states of Germany, together with boot-swab sampling sets for a free and anonymous herd-level paratuberculosis test. Among them, dairy herds and large herds were overrepresented. A hierarchical cluster analysis of the farmers’ answers resulted in four groups that we tagged as ‘informed sceptics’, ‘deniers’, ‘affected supporters’ and ‘free supporters’. In all groups, the majority considered paratuberculosis a threat to the public image of cattle farmers. Nearly all participants wanted to know the paratuberculosis herd status of purchased cattle. In contrast to the supporters, the informed sceptics and the deniers did not consider paratuberculosis a dangerous epizootic disease and would not welcome a mandatory control programme. The deniers and the affected supporters, but not the informed sceptics and the free supporters, assumed that their herd is affected by paratuberculosis. Unlike the deniers, all other groups would enrol in a control programme if the pathogen would have been found in their herd. Protecting future profitability and improving animal health were the two most important motivations to control paratuberculosis in all groups followed by aspects related to the marketing of breeding cattle. Most frequently, the costs and the assumed inaccuracy of diagnostics tests were mentioned as obstacles that hamper programme enrolment.

Conclusions

Significantly different attitudes of farmers regarding paratuberculosis control were identified. Therefore, tailored rather than uniform communication strategies are required to enhance participation in voluntary paratuberculosis control programmes.
Health efficacy of electrically operated automated massage on muscle properties, peripheral circulation, and physio-psychological variables: a narrative review
Authors: Paul Ayan , Usman Juliana , Ahmad Mohd Yazed , Hamidreza Mohafez , Maryam Hadizadeh , Ong Zhi Chao , Hasikin Khairunnisa , Lai Khin Wee
Published: September 2021

Manual massage, commonly used by healthy individuals for well-being, is an ancient practice requiring the intervention of a trained and experienced physiotherapist. On the other hand, automated massage is carried out by machines or modalities without or with minimal control of a human operator. In the present review, we provide a literature analysis to gather the effects of automated massage on muscle properties, peripheral circulation and psychophysiological variables as reported through psychometric and neurophysiological evaluations of each modality ranging from massage beds and whole-body vibrations to robotic massage. A computerized search was performed in Google Scholar, PubMed, and ResearchGate using selected key search terms, and the relevant data were extracted. The findings of this review indicate that for vibration massage, whole-body vibration exposure with relatively lower frequency and magnitude can be safely and effectively used to induce improvements in peripheral circulation. As for massage chair and mechanical bed massage, while most studies report on positive changes, the lack of strong clinical evidence renders these findings largely inconclusive. As for robotic massage, we discuss whether technological advances and collaborative robots might reconcile active and passive modes of action control during a massage and offer new massage perspectives through a stochastic sensorimotor user experience. This transition faculty, from one mode of control to the other, might definitely represent an innovative conceptual approach in terms of human–machine interactions.
Association between lymphocyte count in bronchoalveolar lavage fluid and mortality
Authors: Si Yifu , Shao Juqin , Hu Caibao
Published: September 2021

This is a comment on the paper by Dr. Hirasawa et al. on the predictive value of lymphocyte counts in bronchoalveolar lavage fluid in patients with acute respiratory failure.
Concurrent production of glycyrrhetic acid 3-O-mono-β-d-glucuronide and lignocellulolytic enzymes by solid-state fermentation of a plant endophytic Chaetomium globosum
Authors: Gao Boliang , Xiao Yiwen , Zhang Qian , Sun Junru , Zhang Zhibing , Zhu Du
Published: September 2021

Glycyrrhetic acid 3-O-mono-β-d-glucuronide (GAMG) as an important derivative of glycyrrhizin (GL) shows stronger biological activities and higher sweetness than GL. The biotransformation process is considered as an efficient strategy for GAMG production, due to its mild reaction, high production efficiency and environmentally friendly status. In this study, licorice straw was used for the first time as a medium for GAMG and lignocellulosic enzyme production via solid-state fermentation (SSF) of endophytic fungus Chaetomium globosum DX-THS3. The fermentation conditions including particle size, temperature, seed age, inoculum size, and moisture of substrate were optimized. Furthermore, additional nitrogen sources and carbon sources were screened for GAMG production by C. globosum DX-THS3 of SSF. Under optimal fermentation conditions, the percent conversion of glycyrrhizin reached 90% in 15 days, whereas the control needed 35 days to achieve the same result. The productivity of optimization (P = 2.1 mg/g/day) was 2.33-fold that of non-optimization (P = 0.9 mg/g/day). Meanwhile, high activities of filter paper enzyme (FPase) (245.80 U/g), carboxymethyl cellulase (CMCase) (33.67 U/g), xylanase (83.44 U/g), and β-glucuronidase activity (271.42 U/g) were obtained faster than those in the control during SSF. Our study provides a novel and efficient strategy for GAMG production and indicates C. globosum DX-THS3 as a potential producer of lignocellulolytic enzymes.
Distribution of Panama’s narrow-range trees: are there hot-spots?
Authors: Tokarz Elizabeth , Condit Richard
Published: September 2021

Background

Tree species with narrow ranges are a conservation concern because heightened extinction risk accompanies their small populations. Assessing risks for these species is challenging, however, especially in tropical flora where their sparse populations seldom appear in traditional plots and inventories. Here, we utilize instead large scale databases that combine tree records from many sources to test whether the narrow-range tree species of Panama are concentrated at certain elevations or in certain provinces. Past investigations have suggested that the Choco region of eastern Panama and the high mountains of western Panama may be potential hotspots of narrow-range tree species.

Methods

All individual records were collected from public databases, and the range size of each tree species found in Panama was estimated as a polygon enclosing all its locations. Species with ranges <20,000 km2 were defined as narrow endemics. We divided Panama into geographic regions and elevation zones and counted the number of individual records and the species richness in each, separating narrow-range species from all other species.

Results

The proportion of narrow endemics peaked at elevations above 2000 m, reaching 17.2% of the species recorded. At elevation <1500 m across the country, the proportion was 6-11%, except in the dry Pacific region, where it was 1.5%. Wet forests of the Caribbean coast had 8.4% narrow-range species, slightly higher than other regions. The total number of narrow endemics, however, peaked at mid-elevation, not high elevation, because total species richness was highest at mid-elevation.

Conclusions

High elevation forests of west Panama had higher proportions of narrow endemic trees than low-elevation regions, supporting their hot-spot status, while dry lowland forests had the lowest proportion. This supports the notion that montane forests of Central America should be a conservation focus. However, given generally higher diversity at low- to mid-elevation, lowlands are also important habitats for narrow-range tree species, though conservation efforts here may not protect narrow-range tree species as efficiently.
Cadre parents and their entrepreneur children? The dual-track intergenerational reproduction of elites in China: 1978–2010
Authors: Lu Peng , Fan Xiaoguang
Published: September 2021

This article documents and conceptualizes a mode of reproduction of elites in a society in transition from state domination to market orientation. By focusing on China’ marketization, we explore how parents’ advantageous backgrounds have influenced the chance of their children’s attainment of certain elite positions (administrative, technocratic, or market) and whether these patterns have varied across three periods (1978–1992, 1993–2002, and 2003–2010). Using data obtained from the 2011 China Social Survey, we find that although parents’ advantageous status has a persistent effect on children’s status attainment, the reproduction of the state elite and market elite still follows two separate tracks: the children of cadres do not show significant advantage in the process of becoming entrepreneurs and managerial elites, and the children of entrepreneurial and managerial elites are less likely to join cadres. We also find that the effects of the reproduction model are still enhanced and shaped by state power in different periods. These findings demonstrate the important interplay between family background and contextual inequality and give a deeper understanding of the different trajectories of elites in contemporary China.
Factors Confounding the Athlete Biological Passport: A Systematic Narrative Review
Authors: Krumm Bastien , Faiss Raphael
Published: September 2021

Background

Through longitudinal, individual and adaptive monitoring of blood biomarkers, the haematological module of the athlete biological passport (ABP) has become a valuable tool in anti-doping efforts. The composition of blood as a vector of oxygen in the human body varies in athletes with the influence of multiple intrinsic (genetic) or extrinsic (training or environmental conditions) factors. In this context, it is fundamental to establish a comprehensive understanding of the various causes that may affect blood variables and thereby alter a fair interpretation of ABP profiles.

Methods

This literature review described the potential factors confounding the ABP to outline influencing factors altering haematological profiles acutely or chronically.

Results

Our investigation confirmed that natural variations in ABP variables appear relatively small, likely—at least in part—because of strong human homeostasis. Furthermore, the significant effects on haematological variations of environmental conditions (e.g. exposure to heat or hypoxia) remain debatable. The current ABP paradigm seems rather robust in view of the existing literature that aims to delineate adaptive individual limits. Nevertheless, its objective sensitivity may be further improved.

Conclusions

This narrative review contributes to disentangling the numerous confounding factors of the ABP to gather the available scientific evidence and help interpret individual athlete profiles.
Effects of menopausal hormone therapy on ambulatory blood pressure and arterial stiffness in postmenopausal Korean women with grade 1 hypertension: a randomized, placebo-controlled trial
Authors: Yoon Byung-Koo , Sung Jidong , Song Yun-Mi , Kim Soo-Min , Son Kyung-A , Yoo Jun Hyun , Park Sung-Ji , Kim Duk-Kyung
Published: September 2021

Background

Estrogen therapy in early menopausal women decreases the risk of coronary heart disease and parenteral, but not oral, estrogen is reported to reduce blood pressure (BP). Progestogens are typically added to estrogens to prevent unopposed endometrial stimulation. The effects of progestogen on BP have been less well studied to date. This study was conducted to explore the impacts of micronized progesterone (MP4) combined with percutaneous estradiol gel (PEG) on hemodynamics in postmenopausal Korean women with grade 1 hypertension.

Methods

Fifty-two postmenopausal women (aged 49–75 years) with systolic BP (SBP) of 140–160 mmHg or diastolic BP (DBP) of 90–100 mmHg were randomly assigned for 12 weeks to placebo (n = 16), estrogen therapy (ET) (n = 19) with PEG (0.1 %, 1 g./d), or estrogen + progestogen therapy (EPT, n = 17) with PEG and MP4 (100 mg/d). The primary endpoint was ambulatory BP and the secondary endpoints were arterial stiffness as brachial–ankle pulse-wave velocity (baPWV) and aortic parameters on applanation tonometry.

Results

One woman in the ET group dropped out, so 51 participants were finally analyzed. Outcome measures for ambulatory BP and arterial stiffness were not different between groups. Within-group comparisons showed that EPT significantly decreased daytime heart rate and baPWV: the changes from baseline (mean ± standard deviation) were − 2.5 ± 5.7 bpm (P = 0.03) and − 0.6 ± 1.4 m/s (P = 0.04), respectively. After adjusting for baseline, linear regression analysis revealed a significant difference in the relationship between baseline and 12-week baPWV among groups (P = 0.02). The relationship was significantly different between placebo and ET (P = 0.03) and EPT (P = 0.01), respectively, but not between ET and EPT. Additionally, pooled results of active treatments disclosed that SBP, DBP, PWV, and augmentation index at the aorta were significantly reduced relative to baseline.

Conclusions

There was no difference in ambulatory BP between ET and EPT in postmenopausal Korean women with grade 1 hypertension. Further, ET and EPT similarly decreased baPWV from baseline as compared with placebo. MP4 might not adversely influence estrogen effects on ambulatory BP and arterial stiffness.

Trial registration

Clinical Research Information Registry, KCT0005405, Registered 22 September 2020 - Retrospectively registered, https://cris.nih.go.kr/cris/search/detailSearch.do?all_type=Y&search_page=L&pageSize=10&page=1&seq=17608&search_lang=E.