bluuebunny/crossref_metadata_2025_split huggingface dataset:
Turning the tide on Alzheimer’s disease: modulation of γ-secretase
Authors: Luo Joanna E. , Li Yue-Ming 
Published: January 2022

AbstractAlzheimer’s disease (AD) is the most common type of neurodegenerative disorder. Amyloid-beta (Aβ) plaques are integral to the “amyloid hypothesis,” which states that the accumulation of Aβ peptides triggers a cascade of pathological events leading to neurodegeneration and ultimately AD. While the FDA approved aducanumab, the first Aβ-targeted therapy, multiple safe and effective treatments will be needed to target the complex pathologies of AD. γ-Secretase is an intramembrane aspartyl protease that is critical for the generation of Aβ peptides. Activity and specificity of γ-secretase are regulated by both obligatory subunits and modulatory proteins. Due to its complex structure and function and early clinical failures with pan inhibitors, γ-secretase has been a challenging drug target for AD. γ-secretase modulators, however, have dramatically shifted the approach to targeting γ-secretase. Here we review γ-secretase and small molecule modulators, from the initial characterization of a subset of NSAIDs to the most recent clinical candidates. We also discuss the chemical biology of γ-secretase, in which small molecule probes enabled structural and functional insights into γ-secretase before the emergence of high-resolution structural studies. Finally, we discuss the recent crystal structures of γ-secretase, which have provided valuable perspectives on substrate recognition and molecular mechanisms of small molecules. We conclude that modulation of γ-secretase will be part of a new wave of AD therapeutics.
Y chromosome is moving out of sex determination shadow
Authors: Heydari Raheleh , Jangravi Zohreh , Maleknia Samaneh , Seresht-Ahmadi Mehrshad , Bahari Zahra , Salekdeh Ghasem Hosseini , Meyfour Anna 
Published: January 2022

AbstractAlthough sex hormones play a key role in sex differences in susceptibility, severity, outcomes, and response to therapy of different diseases, sex chromosomes are also increasingly recognized as an important factor. Studies demonstrated that the Y chromosome is not a ‘genetic wasteland’ and can be a useful genetic marker for interpreting various male-specific physiological and pathophysiological characteristics. Y chromosome harbors male‑specific genes, which either solely or in cooperation with their X-counterpart, and independent or in conjunction with sex hormones have a considerable impact on basic physiology and disease mechanisms in most or all tissues development. Furthermore, loss of Y chromosome and/or aberrant expression of Y chromosome genes cause sex differences in disease mechanisms. With the launch of the human proteome project (HPP), the association of Y chromosome proteins with pathological conditions has been increasingly explored. In this review, the involvement of Y chromosome genes in male-specific diseases such as prostate cancer and the cases that are more prevalent in men, such as cardiovascular disease, neurological disease, and cancers, has been highlighted. Understanding the molecular mechanisms underlying Y chromosome-related diseases can have a significant impact on the prevention, diagnosis, and treatment of diseases.
Modeling human neurodevelopmental diseases with brain organoids
Authors: Lu Xiaoxiang , Yang Jiajie , Xiang Yangfei 
Published: January 2022

AbstractStudying the etiology of human neurodevelopmental diseases has long been a challenging task due to the brain’s complexity and its limited accessibility. Human pluripotent stem cells (hPSCs)-derived brain organoids are capable of recapitulating various features and functionalities of the human brain, allowing the investigation of intricate pathogenesis of developmental abnormalities. Over the past years, brain organoids have facilitated identifying disease-associated phenotypes and underlying mechanisms for human neurodevelopmental diseases. Integrating with more cutting-edge technologies, particularly gene editing, brain organoids further empower human disease modeling. Here, we review the latest progress in modeling human neurodevelopmental disorders with brain organoids.
Fluctuation of bone turnover markers’ levels in samples of gingival crevicular fluid after orthodontic stimulus: a systematic review
Authors: Kakali L. , Giantikidis I. , Sifakakis I. , Kalimeri E. , Karamani I. , Mavrogonatou E. , Kloukos D. 
Published: January 2022

Abstract
Background
The aim of the present study was to provide an overview of gingival crevicular fluid (GCF) bone turnover markers (BTMs) concerning the physiology of orthodontic tooth movement (OTM) and assess their potential contributions to regulating bone remodeling, that could prove useful in designing future approaches to modulating orthodontic tooth movement.

Methods
Multiple electronic databases (MEDLINE/PubMed, Ovid MEDLINE, Ovid Embase, LILACS, and Cochrane Library) were searched up to October 1st, 2020. Randomized controlled trials (RCTs), controlled clinical trials, observational studies of prospective and retrospective designs, and cross-sectional studies reporting on levels of BTMs in GCF were eligible for inclusion. The quality of the included RCTs was assessed per the revised Cochrane risk of bias tool for randomized trials (RoB 2.0), whereas the risk of bias of the included cohort studies was assessed using the Risk Of Bias In Non-randomized Studies of Interventions tool.

Results
Five RCTs, 9 prospective cohort studies, and 1 cross-sectional study fulfilled the inclusion criteria. The risk of bias was deemed as high for the RCTs and 4 of the prospective studies and moderate for the rest of the studies. The following biomarkers for bone formation were assessed: bone alcaline phosphatase (BALP), alcaline phosphatase (ALP), and osteocalcin (OC). For bone resorption, the following BTMs were assessed: deoxypyridinoline (DPD) and pyridinoline (PYD), N-terminal telopeptide (NTX), osteopontin (OPN), and tartrate-resistant acid phosphatase (TRAP). The follow-up period ranged mainly from baseline to 45 days, although one study had an expanded follow-up period of up to 16 months. The results of the included studies comparing different BTMs were heterogeneous and qualitatively reported.

Conclusions
Current evidence continues to support the potential for BTMs to provide clinically useful information particularly for adjusting or standardizing the orthodontic stimulus. The present systematic review has retrieved studies of high, overall, risk of bias, and has unveiled a substantial clinical and methodological heterogeneity among included studies. Further data of the relationships between the clinical assays and the physiological or pre-analytical factors contributing to variability in BTMs’ concentrations are required.

Systematic review registration
CRD42020212056.
Circumcentering approximate reflections for solving the convex feasibility problem
Authors: Araújo G. H. M. , Arefidamghani R. , Behling R. , Bello-Cruz Y. , Iusem A. , Santos L.-R. 
Published: January 2022

AbstractThe circumcentered-reflection method (CRM) has been applied for solving convex feasibility problems. CRM iterates by computing a circumcenter upon a composition of reflections with respect to convex sets. Since reflections are based on exact projections, their computation might be costly. In this regard, we introduce the circumcentered approximate-reflection method (CARM), whose reflections rely on outer-approximate projections. The appeal of CARM is that, in rather general situations, the approximate projections we employ are available under low computational cost. We derive convergence of CARM and linear convergence under an error bound condition. We also present successful theoretical and numerical comparisons of CARM to the original CRM, to the classical method of alternating projections (MAP), and to a correspondent outer-approximate version of MAP, referred to as MAAP. Along with our results and numerical experiments, we present a couple of illustrative examples.
Changes in sedentary behavior patterns during the transition from childhood to adolescence and their association with adiposity: a prospective study based on compositional data analysis
Authors: Rubín Lukáš , Gába Aleš , Pelclová Jana , Štefelová Nikola , Jakubec Lukáš , Dygrýn Jan , Hron Karel 
Published: January 2022

Abstract
Background
To date, no longitudinal study using a compositional approach has examined sedentary behavior (SB) patterns in relation to adiposity in the pediatric population. Therefore, our aims were to (1) investigate the changes in SB patterns and adiposity from childhood to adolescence, (2) analyze the prospective compositional associations between changes in SB patterns and adiposity, and (3) estimate the changes in adiposity associated with substituting SB with physical activity (PA) of different intensities.

Methods
The study presents a longitudinal design with a 5-year follow-up. A total of 88 participants (61% girls) were included in the analysis. PA and SB were monitored for seven consecutive days using a hip-worn accelerometer. Adiposity markers (fat mass percentage [FM%], fat mass index [FMI], and visceral adiposity tissue [VAT]) were assessed using the multi-frequency bioimpedance analysis. The prospective associations were examined using compositional data analysis.

Results
Over the follow-up period, the proportion of time spent in total SB increased by 154.8 min/day (p < 0.001). The increase in total SB was caused mainly by an increase in middle and long sedentary bouts, as these SB periods increased by 79.8 min/day and 62.0 min/day (p < 0.001 for both), respectively. FM%, FMI, and VAT increased by 2.4% points, 1.0 kg/m2, and 31.5 cm2 (p < 0.001 for all), respectively. Relative to the remaining movement behaviors, the increase in time spent in middle sedentary bouts was significantly associated with higher FM% (βilr1 = 0.27, 95% confidence interval [CI]: 0.02 to 0.53) at follow-up. Lower VAT by 3.3% (95% CI: 0.8 to 5.7), 3.8% (95% CI: 0.03 to 7.4), 3.9% (95% CI: 0.8 to 6.9), and 3.8% (95% CI: 0.7 to 6.9) was associated with substituting 15 min/week spent in total SB and in short, middle, and long sedentary bouts, respectively, with an equivalent amount of time spent in vigorous PA.

Conclusions
This study showed unfavorable changes in SB patterns and adiposity status in the transition from childhood to adolescence. Incorporating high-intensity PA at the expense of SB appears to be an appropriate approach to reduce the risk of excess adiposity in the pediatric population.
Concordance of the cardiovascular patient education with the principles of Andragogy model
Authors: Niksadat Negin , Rakhshanderou Sakineh , Negarandeh Reza , Ramezankhani Ali , Farahani Ali Vasheghani , Ghaffari Mohtasham 
Published: January 2022

Abstract
Background
Patient education is a critical aspect of patient care and is considered a vital part of self-care (especially in patients with cardiovascular disease (CVD)) and health promotion. The literature supports incorporating the principles of the andragogy model (adult learning) into patient education. This study aimed to determine the concordance of the CVD patient education with the principles of the andragogy model.

Methods
This cross-sectional survey was conducted on 384 adult CVD patients from 2 selected hospitals of Tehran. The sampling method was convenient, and the data collection tool was a researcher-made questionnaire based on the principles of the andragogy model. Data were analyzed using SPSS16 statistical software.

Results
The mean age of the patients was 55.69 ± 13.01 years old. Frequency of distribution of the patients who, in total, selected the items of 4 or 5 for respecting the principles of andragogy model was as follows: 68.16% for the motivation, 66.29% for the need, 66.03% for the orientation, 54.16% for the experiences, 51.55% for the self-concept, and 44.65% for the readiness principle.
Also, three principles of motivation (77.37) need (74.97), and orientation (74.78) had the highest mean, respectively, in terms of adhering to this model. But the most common problems in patient education were related to the principles of readiness (64.35), self-concept (68.19), and experiences (77.71) with the lowest mean.

Conclusions
The findings of this study provided valuable information on the flaws in patient education, including ignoring and disrespecting the principles of adult education. Correcting these detected defects and providing feedback to health professionals can improve the quality of patient education programs and patient satisfaction. Also, it empowers healthcare providers, patients, and families through effective education strategies.
Recruitment, adherence and attrition challenges in internet-based indicated prevention programs for eating disorders: lessons learned from a randomised controlled trial of ProYouth OZ
Authors: Ali Kathina , Fassnacht Daniel B. , Farrer Louise M. , Rieger Elizabeth , Moessner Markus , Bauer Stephanie , Griffiths Kathleen M. 
Published: January 2022

AbstractBackgroundGrowing evidence supports the effectiveness of Internet-based prevention programs for eating disorders, but the adjunctive benefit of synchronous peer support has yet to be investigated. In the current study, a randomised controlled trial was conducted to evaluate the effectiveness of an indicated Internet-based prevention program (ProYouth OZ)with and without peer-to-peer support in reducing disordered eating behaviours and attitudes.MethodFifty young adults (18–25 years) with eating disorder symptoms were randomised to one of three study conditions: (1)ProYouth OZ(without peer-to-peer support), (2)ProYouth OZ Peers(with peer-to-peer support), and (3) a waitlist control group. Outcomes were assessed at three different time points. Eating disorder symptoms (primary outcome) were measured with the Eating Disorder Examination Questionnaire.ResultsOf 415 screened participants, 73 (17.6%) were eligible and 213 (51.3%) excluded due to severe eating disorder symptoms. Fifteen participants (30%) completed the post-intervention survey. Of the two intervention groups, 20.6% failed to access any component of the program. Of 17ProYouth OZ Peersparticipants, 58.8% attended at least one chat session, 20% attended 2–5 sessions, and 11.8% attended all six sessions. Due to limited outcome data, it was not possible to statistically examine between-group differences in outcomes. Visual inspection of individual profiles revealed that bothProYouth OZ Peersparticipants who completed the post-intervention survey showed a decrease in disordered eating compared with only one of the six completers inProYouth OZ.ConclusionFindings highlight the challenges of trialling Internet-based eating disorder prevention programs in the community. The study identified a large group of emerging adults with eating disorders who were interested in an Internet-based program, suggesting a high level of unmet need. Future research on synchronous peer-to-peer support in Internet-based prevention for eating disorders is warranted. Further studies are required to identify optimal strategies for reaching this population (e.g., online vs. offline) and evaluating the effectiveness of a range of strategies for promoting engagement. Finally, there is an urgent need to develop innovative widely accessible interventions for individuals who experience clinically relevant eating disorder symptomatology but may not be ready or able to seek professional face-to-face treatment.Trial registration: ACTRN12615001250527, Registered 16 November 2015,https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12615001250527
Relating a concordance-based cloze test to the model of communicative language ability: a verbal protocol study
Authors: Kongsuwannakul Kunlaphak 
Published: January 2022

AbstractThe literature of empirical studies on the concordance-based cloze test (ConCloze) is far and few between. This is despite the fact that it has a potential for item writing without the aid of native speakers and for making use of corpus-based technology in task design. This article explores the test-taking processes and strategies of a ConCloze item variant. The aim is to investigate the substantive aspect of the construct validity for the item type and increase the generalizability of the findings in the universe of admissible observations. The sample consists of 14 non-native English users who are in higher education and engage with 3 test tasks each, totaling 42 verbal reports. The sampling method is purposive sampling, in which their first language profiles are maximized in terms of heterogeneity for increased power of generalization. It is found that Reading concordance lines and recognizing clue words inside is a major process, and Assessing item components and testing a meaningful compatibility of a word in context a secondary one. A model of communicative language ability is used to provide a context for task use in this study, where strategic competence is represented in ConCloze substantive validity.
Exploring jump back behavior patterns and reasons in e-book system
Authors: Ma Boxuan , Lu Min , Taniguchi Yuta , Konomi Shin’ichi 
Published: January 2022

AbstractWith the increasing use of digital learning materials in higher education, the accumulated operational log data provide a unique opportunity to analyzing student learning behaviors and their effects on student learning performance to understand how students learn with e-books. Among the students’ reading behaviors interacting with e-book systems, we find that jump-back is a frequent and informative behavior type. In this paper, we aim to understand the student’s intention for a jump-back using user learning log data on the e-book materials of a course in our university. We at first formally define the “jump-back” behaviors that can be detected from the click event stream of slide reading and then systematically study the behaviors from different perspectives on the e-book event stream data. Finally, by sampling 22 learning materials, we identify six reading activity patterns that can explain jump backs. Our analysis provides an approach to enriching the understanding of e-book learning behaviors and informs design implications for e-book systems.
Development of a decision flowchart to identify the patients need high-dose vancomycin in early phase of treatment
Authors: Yamaguchi Ryo , Kani Hiroko , Yamamoto Takehito , Tanaka Takehiro , Suzuki Hiroshi 
Published: January 2022

Abstract
Background
The standard dose of vancomycin (VCM, 2 g/day) sometimes fails to achieve therapeutic concentration in patients with normal renal function. In this study, we aimed to identify factors to predict patients who require high-dose vancomycin (> 2 g/day) to achieve a therapeutic concentration and to develop a decision flowchart to select these patients prior to VCM administration.

Methods
Patients who had an estimated creatinine clearance using the Cockcroft–Gault equation (eCCr) of ≥50 mL/min and received intravenous VCM were divided into 2 cohorts: an estimation set (n = 146, from April to September 2016) and a validation set (n = 126, from October 2016 to March 2017). In each set, patients requiring ≤2 g/day of VCM to maintain the therapeutic trough concentration (10–20 μg/mL) were defined as standard-dose patients, while those who needed > 2 g/day were defined as high-dose patients. Univariate and multivariate logistic regression analysis was performed to identify the predictive factors for high-dose patients and decision tree analysis was performed to develop decision flowchart to identify high-dose patients.

Results
Among the covariates analyzed, age and eCCr were identified as independent predictors for high-dose patients. Further, the decision tree analysis revealed that eCCr (cut off value = 81.3 mL/min) is the top predictive factor and is followed by age (cut off value = 58 years). Based on these findings, a decision flowchart was constructed, in which patients with eCCr ≥81.3 mL/min and age < 58 years were designated as high-dose patients and other patients were designated as standard-dose patients. Subsequently, we applied this decision flowchart to the validation set and obtained good predictive performance (positive and negative predictive values are 77.6 and 84.4%, respectively).

Conclusion
These results suggest that the decision flowchart constructed in this study provides an important contribution for avoiding underdosing of VCM in patients with eCCr of ≥50 mL/min.
Targeted deletion of liver-expressed Choriogenin L results in the production of soft eggs and infertility in medaka, Oryzias latipes
Authors: Murata Kenji , Kinoshita Masato 
Published: January 2022

AbstractEgg envelopes (chorions) in medaka, Oryzias latipes, are composed of three major glycoproteins: ZI-1, − 2, and − 3. These gene-encoded chorion glycoproteins are expressed in the liver and/or ovarian oocytes of sexually mature female fish. In medaka, the glycoproteins produced in the female liver are induced by estrogen as Choriogenin (Chg.) H and Chg. H minor (m), which correspond to the zona pellucida (ZP) B (ZPB) protein in mammals, and Chg. L, which corresponds to ZPC in mammals. Chg. H, Chg. Hm, and Chg. L, are then converted to ZI-1, − 2, and − 3, respectively, during oogenesis in medaka ovaries.In the present study, we established a medaka line in which the chg.l gene was inactivated using the transcription activator-like effector nuclease (TALEN) technique. Neither intact chg.l transcripts nor Chg. L proteins were detected in livers of sexually mature female homozygotes for the mutation (homozygous chg.l knockout: chg.l−/−). The chg.l−/− females spawned string-like materials containing “smashed eggs.” Closer examination revealed the oocytes in the ovaries of chg.l−/− females had thin chorions, particularly at the inner layer, despite a normal growth rate. In comparing chorions from normal (chg.l+/+) and chg.l−/− oocytes, the latter exhibited abnormal architecture in the chorion pore canals through which the oocyte microvilli pass. These microvilli mediate the nutritional exchange between the oocyte and surrounding spaces and promote sperm-egg interactions during fertilization. Thus, following in vitro fertilization, no embryos developed in the artificially inseminated oocytes isolated from chg.l−/− ovaries. These results demonstrated that medaka ZI-3 (Chg.L) is the major component of the inner layer of the chorion, as it supports and maintains the oocyte’s structural shape, enabling it to withstand the pressures exerted against the chorion during spawning, and is essential for successful fertilization. Therefore, gene products of oocyte-specific ZP genes that may be expressed in medaka oocytes cannot compensate for the loss Chg. L function to produce offspring for this species.