bluuebunny/crossref_metadata_2025 huggingface dataset:
Turning the tide on Alzheimer’s disease: modulation of γ-secretase
Authors: Luo Joanna E. , Li Yue-Ming
Published: January 2022

Alzheimer’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

Although 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

Studying 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

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

The 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

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

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

Background

Growing 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.

Method

Fifty 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.

Results

Of 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.

Conclusion

Findings 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

The 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

With 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

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

Egg 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.
Eales’ disease: epidemiology, diagnostic and therapeutic concepts
Authors: Murillo López Sergio , Medina Medina Silvia , Murillo López Fernando
Published: January 2022

Background

To describe the epidemiological traits, clinical characteristics, diagnostic procedures, therapeutic interventions and evolution in a large series of patients with diagnosis of Eales’ disease.

Methods

A clinical retrospective review of patients with Eales’ disease, evaluated and treated between April 2009 and April 2018, with a 1-year minimum follow-up. Thirty patients (59 eyes), were included. Age, sex, laboratory results (CBC, glycemia, protein electrophoresis, ACE levels) immunological profile and a Quantiferon-TB Gold Plus test were recorded. The patients were divided into groups according to their evolution, medical or surgical treatment, and visual outcomes.

Results

Seventeen male patients and 13 female patients were included, and their ages ranged from 14 to 35 years. The Quantiferon-TB Gold Plus test was positive in 25 patients. Twenty-eight patients had unilateral vitreous hemorrhage, 10 of whom presented with vasculitis and non-perfusion areas in the contralateral eye, 9 presented contralateral peripheral neovascularization and 9 had contralateral fibrovascular proliferation. The remaining 2 patients presented with a rhegmatogenous retinal detachment. In 6 patients, conservative treatment with intravitreal anti-VEGF injections and photocoagulation was performed after the hemorrhage cleared. Twenty-two patients, required vitrectomy, with good visual outcomes. Macular edema was found in 16 eyes, which responded to periocular and/or systemic corticosteroid therapy, except for 9 eyes that required intravitreal bevacizumab, with complete resolution in 7 eyes and partial resolution in 2 eyes.

Conclusions

Eales’ disease is a pathology of significant prevalence in our country. The distribution according to sex, tends to be equivalent. The etiology, even when it is not specifically determined, according to laboratory tests, confirms the probable immunologic response in the presence of Mycobacterium tuberculosis antigens. This is still a diagnosis of exclusion, and therefore, it is advisable to perform a complete laboratory work-up in each case. Timely application of laser and other medical treatments, help to avoid progression to more advanced stages and their complications. The surgical treatment of vitrectomy for vitreous hemorrhage, and/or tractional vitreous detachment yields good primary anatomical and functional outcomes. Secondary macular edema responds to periocular and intravitreal corticosteroids, and in refractory cases, the use of anti-VEGF therapy leads to an effective resolution.
Static CT myocardial perfusion imaging: image quality, artifacts including distribution and diagnostic performance compared to 82Rb PET
Authors: Inácio João R. , Srinivasan Sriraag Balaji , Ruddy Terrence D. , deKemp Robert A. , Rybicki Frank , Beanlands Rob S. , Chow Benjamin J. W. , Dwivedi Girish
Published: January 2022

Background

Rubidium-82 positron emission tomography (82Rb PET) MPI is considered a noninvasive reference standard for the assessment of myocardial perfusion in coronary artery disease (CAD) patients. Our main goal was to compare the diagnostic performance of static rest/ vasodilator stress CT myocardial perfusion imaging (CT-MPI) to stress/ rest 82Rb PET-MPI for the identification of myocardial ischemia.

Methods

Forty-four patients with suspected or diagnosed CAD underwent both static CT-MPI and 82Rb PET-MPI at rest and during pharmacological stress. The extent and severity of perfusion defects on PET-MPI were assessed to obtain summed stress score, summed rest score, and summed difference score. The extent and severity of perfusion defects on CT-MPI was visually assessed using the same grading scale. CT-MPI was compared with PET-MPI as the gold standard on a per-territory and a per-patient basis.

Results

On a per-patient basis, there was moderate agreement between CT-MPI and PET-MPI with a weighted 0.49 for detection of stress induced perfusion abnormalities. Using PET-MPI as a reference, static CT-MPI had 89% sensitivity (SS), 58% specificity (SP), 71% accuracy (AC), 88% negative predictive value (NPV), and 59% positive predictive value (PPV) to diagnose stress-rest perfusion deficits on a per-patient basis. On a per-territory analysis, CT-MPI had 73% SS, 65% SP, 67% AC, 90.8% NPV, and 34% PPV to diagnose perfusion deficits.

Conclusions

CT-MPI has high sensitivity and good overall accuracy for the diagnosis of functionally significant CAD using 82Rb PET-MPI as the reference standard. CT-MPI may play an important role in assessing the functional significance of CAD especially in combination with CCTA.
Delta-8-THC: Delta-9-THC’s nicer younger sibling?
Authors: Kruger Jessica S. , Kruger Daniel J.
Published: January 2022

Background

Products containing delta-8-THC became widely available in most of the USA following the 2018 Farm Bill and by late 2020 were core products of hemp processing companies, especially where delta-9-THC use remained illegal or required medical authorization. Research on experiences with delta-8-THC is scarce, some state governments have prohibited it because of this lack of knowledge.

Objective

We conducted an exploratory study addressing a broad range of issues regarding delta-8-THC to inform policy discussions and provide directions for future systematic research.

Methods

We developed an online survey for delta-8-THC consumers, including qualities of delta-8-THC experiences, comparisons with delta-9-THC, and open-ended feedback. The survey included quantitative and qualitative aspects to provide a rich description and content for future hypothesis testing. Invitations to participate were distributed by a manufacturer of delta-8-THC products via social media accounts, email contact list, and the Delta8 Reddit.com discussion board. Participants (N = 521) mostly identified as White/European American (90%) and male (57%). Pairwise t tests compared delta-8-THC effect rating items; one-sample t tests examined responses to delta-9-THC comparison items.

Results

Most delta-8-THC users experienced a lot or a great deal of relaxation (71%); euphoria (68%) and pain relief (55%); a moderate amount or a lot of cognitive distortions such as difficulty concentrating (81%), difficulties with short-term memory (80%), and alerted sense of time (74%); and did not experience anxiety (74%) or paranoia (83%). Participants generally compared delta-8-THC favorably with both delta-9-THC and pharmaceutical drugs, with most participants reporting substitution for delta-9-THC (57%) and pharmaceutical drugs (59%). Participant concerns regarding delta-8-THC were generally focused on continued legal access.

Conclusions

Delta-8-THC may provide much of the experiential benefits of delta-9-THC with lesser adverse effects. Future systematic research is needed to confirm participant reports, although these studies are hindered by the legal statuses of both delta-8-THC and delta-9-THC. Cross-sector collaborations among academics, government officials, and representatives from the cannabis industry may accelerate the generation of knowledge regarding delta-8-THC and other cannabinoids. A strength of this study is that it is the first large survey of delta-8 users, limitations include self-report data from a self-selected convenience sample.
Effect of urbanization on heavy metal contamination: a study on major townships of Kannur District in Kerala, India
Authors: Shimod K. P. , Vineethkumar V. , Prasad T. K. , Jayapal G.
Published: January 2022

Background

In the last few decades, the air, water, and soil are contaminated due to different anthropogenic activities and severely affect the environmental quality. Pollution is the harmful effect and creates undesirable changes in the land use and land cover pattern. The growth of urbanization leads to the degradation of the ecosystem and ultimately affects the living and non-living organisms. In view of these, the present investigation is carried out to assess the heavy metal pollution in major towns due to the impact of urbanization in Kannur district and desirable conclusions were drawn.

Results

The results shows that higher level of heavy metal pollution is observed in major towns of Kannur district.

Conclusion

The heavy metal contamination in the major towns of Kannur district is mainly due the anthropogenic activities. The discharge of domestic effluents and industrial waste is the major source of heavy metal pollution. In-depth studies and proper waste management plans are needed to decrease the level of heavy metal contamination prevailing in the study area.
A case of Landau-Kleffner syndrome with SLC26A4-related hearing impairment
Authors: Gong Pan , Jiao Xianru , Yang Zhixian
Published: January 2022

Background

Landau-Kleffner syndrome (LKS) is an acquired aphasia and electroencephalogram (EEG) abnormalities mainly in temporoparietal areas. SLC26A4 mutations can cause hearing loss associated with enlarged vestibular aqueduct (EVA).

Case presentations

We report a case of LKS in a 5-year-old boy with non-syndromic EVA due to homozygous mutations of c.919-2A>G (IVS7-2A>G) in SLC26A4. He had normal language development before 2 years old. At the age of 2.5 years, he was admitted to the hospital due to remarkable language delay, and diagnosed with hearing loss with EVA. The seizures started at 4.4 years of age and EEG recording showed electrical status epilepticus during sleep (ESES) with a posterior-temporal predominance. He received cochlear implantation in the right ear at 4.7 years of age, which improved his hearing and language skills. The nocturnal focal motor seizures recurred at 4.9 years of age. Then a remarkable inability to respond to calls and reduction in spontaneous speech were noticed. He was treated with methylprednisolone at 5 years old, which controlled the seizures, suppressed ESES, and remarkably improved the language ability. The absence of seizures maintained until the last follow-up at 5.3 years of age, with further improvements in EEG recording and language ability.

Conclusions

The co-existence of LKS and hearing loss caused by SLC26A4 mutations increases the difficulty of LKS diagnosis, especially in the presence of hearing loss and impaired language skills. EEG discharges predominantly in temporoparietal areas, the occurrence of ESES, and language improvement after antiepileptic medications are potential indicators for LKS diagnosis.
Imaging spectrum of acquired uterine vascular abnormalities with angiographic correlates, a pictorial review
Authors: Masood Laiba , Rana Atif I. , Khan Zahid A. , Nosheen Saman , Ali Haider , Anwar Jamshed
Published: January 2022

Background

Acquired uterine arterial anomalies, including uterine artery pseudoaneurysms (UAP), arteriovenous malformations (AVMs) and arteriovenous fistulae (AFVs), are rare presenting causes of abnormal uterine bleeding. Timely diagnosis is essential for safe and effective treatment, avoiding life-threatening haemorrhage resulting from erroneous uterine curettage due to misdiagnosing these as other more common differentials.

Main text

This pictorial review discusses the ultrasound (USG), CT and MRI features of various acquired uterine vascular abnormalities with angiographic correlates.

Conclusion

Acquired uterine arteriovenous injuries are a fundamental cause of dysfunctional intractable bleeding recalcitrant to traditional conservative management. Endovascular transcatheter uterine artery embolisation is an increasingly popular and safe mode of treatment, especially in young patients desiring to have the option of future pregnancies, with lesser morbidity and in-hospital stay duration.
Diffusion tensor imaging of dorsal stream language areas in patients with post-stroke aphasia
Authors: Elmongui Azza , AbdelRazek Ahmed , Abou-Elsaad Tamer , Belal Tamer , Ibrahim Noha , Alnaghy Eman
Published: January 2022

Background

Aphasia complicating stroke occurs due to language deficits that decrease communication abilities and functional independence. Our study aims to assess fractional anisotropy (FA) and mean diffusivity (MD) parameters of diffusion tensor imaging (DTI) of the dorsal stream language areas in patients with post-stroke aphasia. It was conducted on 27 patients with post-stroke aphasia and 27 age- and sex-matched controls who underwent DTI of the brain. FA and MD values of Broca's area (BA), Wernick's area (WA), superior longitudinal fasciculus (SLF), and arcuate fasciculus (AF), and number of tract fibers (TF) of AF and SLF were calculated. Results were correlated with National Institutes of Health Stroke Scale (NIHSS), Arabic version of Comprehensive Aphasia Test (Arabic CAT), and Mansoura Arabic Screening Aphasia Test (MASAT).

Results

FA of AF and SLF in patients was significantly lower (P = 0.001) than controls. MD of AF and SLF in patients was significantly higher (P = 0.001) than controls. The mean volume TF of AF and SLF in patients was significantly (P = 0.001) lower than the mean volume in controls for AF and SLF. FA cutoff for AF was 0.34 and for SLF, it was 0.35 with sensitivity, specificity, and accuracy (85.2%, 62.1%, 73.2%) for AF, (74.1%, 69%, 71.4%) for SLF, respectively. MD cutoff value for AF was 0.87, and 0.84 for SLF with sensitivity, specificity, and accuracy (63%, 72.4%, 67.8%) for AF, (81.5%, 79.3%, 80.4%) for SLF, respectively. Cutoff TF of AF was 1728 and for SLF it was 601 with sensitivity, specificity, and accuracy (88.9%, 72.4%, 80.4%) for AF and (85.2%, 85.2%, 78.6%) for SLF, respectively.

Conclusions

DTI is a non-invasive promising method that can be used to assess language areas in patients with post-stroke aphasia.
Coordination of sustainable financing for evidence-based youth mental health treatments: protocol for development and evaluation of the fiscal mapping process
Authors: Dopp Alex R. , Gilbert Marylou , Silovsky Jane , Ringel Jeanne S. , Schmidt Susan , Funderburk Beverly , Jorgensen Ashley , Powell Byron J. , Luke Douglas A. , Mandell David , Edwards Daniel , Blythe Mellicent , Hagele Dana
Published: January 2022

Background

Sustained delivery of evidence-based treatments (EBTs) is essential to addressing the public health and economic impacts of youth mental health problems, but is complicated by the limited and fragmented funding available to youth mental health service agencies (hereafter, “service agencies”). Strategic planning tools are needed that can guide these service agencies in their coordination of sustainable funding for EBTs. This protocol describes a mixed-methods research project designed to (1) develop and (2) evaluate our novel fiscal mapping process that guides strategic planning efforts to finance the sustainment of EBTs in youth mental health services.

Method

Participants will be 48 expert stakeholder participants, including representatives from ten service agencies and their partners from funding agencies (various public and private sources) and intermediary organizations (which provide guidance and support on the delivery of specific EBTs). Aim 1 is to develop the fiscal mapping process: a multi-step, structured tool that guides service agencies in selecting the optimal combination of strategies for financing their EBT sustainment efforts. We will adapt the fiscal mapping process from an established intervention mapping process and will incorporate an existing compilation of 23 financing strategies. We will then engage participants in a modified Delphi exercise to achieve consensus on the fiscal mapping process steps and gather information that can inform the selection of strategies. Aim 2 is to evaluate preliminary impacts of the fiscal mapping process on service agencies’ EBT sustainment capacities (i.e., structures and processes that support sustainment) and outcomes (e.g., intentions to sustain). The ten agencies will pilot test the fiscal mapping process. We will evaluate how the fiscal mapping process impacts EBT sustainment capacities and outcomes using a comparative case study approach, incorporating data from focus groups and document review. After pilot testing, the stakeholder participants will conceptualize the process and outcomes of fiscal mapping in a participatory modeling exercise to help inform future use and evaluation of the tool.

Discussion

This project will generate the fiscal mapping process, which will facilitate the coordination of an array of financing strategies to sustain EBTs in community youth mental health services. This tool will promote the sustainment of youth-focused EBTs.
Hydrogel based tissue engineering and its future applications in personalized disease modeling and regenerative therapy
Authors: Chaudhary Shikha , Chakraborty Eliza
Published: January 2022

Background

Evolution in the in vitro cell culture from conventional 2D to 3D technique has been a significant accomplishment. The 3D culture models have provided a close and better insight into the physiological study of the human body. The increasing demand for organs like liver, kidney, and pancreas for transplantation, rapid anti-cancer drug screening, and the limitations associated with the use of animal models have attracted the interest of researchers to explore 3D organ culture.

Main body

Natural, synthetic, and hybrid material-based hydrogels are being used as scaffolds in 3D culture and provide 'close-to-in vivo’ structures. Organoids: the stem cell-derived small size 3D culture systems are now favored due to their ability to mimic the in-vivo conditions of organ or tissue and this characteristic has made it eligible for a variety of clinical applications, drug discovery and regenerative medicine are a few of the many areas of application. The use of animal models for clinical applications has been a long-time ethical and biological challenge to get accurate outcomes. 3D bioprinting has resolved the issue of vascularization in organoid culture to a great extent by its layer-by-layer construction approach. The 3D bioprinted organoids have a popular application in personalized disease modeling and rapid drug development and therapeutics.

Short conclusions

This review paper, focuses on discussing the novel organoid culture approach, its advantages and limitations, and potential applications in a variety of life science areas namely cancer research, cell therapy, tissue engineering, and personalized medicine and drug discovery.

Graphical Abstract
Undergraduate Research in International Contexts
Authors: Belhiah Hassan
Published: January 2022

This article seeks to contribute to our understanding of the challenges and opportunities afforded by undergraduate research in the context of changing English departments in international contexts. English has been witnessing unprecedented growth in the Middle East and North Africa (MENA) region thanks to globalization, the Internet, and the internationalization of higher education. In this article, I reflect on my experience with undergraduate research in the MENA region, focusing on the challenges I had encountered and strategies for engendering a successful undergraduate research experience.
Formalizing Curiosity
Authors: Behling Laura L.
Published: January 2022

Faculty and students in English and other humanities disciplines engage in undergraduate research and scholarship. Administrative support ensures institutional practices, policies such as those focused on tenure and promotion, and rewards are in place to encourage students as scholars, mentored by faculty. Such administrative leadership demonstrates an inclusive recognition that all disciplines engage in undergraduate scholarship; contributes to recruitment and retention efforts; positively impacts on student learning; and effectively promotes the institution, faculty, and students.
Energy security under the context of critical security studies
Authors: Μελάς Ματθαίος
Published: January 2022

Ο στόχος αυτής της διδακτορικής διατριβής είναι να εξετάσει, μέσω της θαλάσσιας περιοχής του Barents, με ποιον τρόπο οι critical security studies μπορούν να διευκολύνουν την ανάλυση των αναδυόμενων σχέσεων μεταξύ της Ευρωπαϊκής Ένωσης, της Ρωσίας και της Νορβηγίας στην Αρκτική. Συγκεκριμένα, με ποιους τρόπους μπορούν να εφαρμοστούν οι critical security studies στην ενεργειακή ασφάλεια της ΕΕ σε σχέση με τη Νορβηγία και τη Ρωσία; Σε ποιο βαθμό τα ενεργειακά αποθέματα της περιοχής Barents δημιουργούν αλληλεπιδράσεις μεταξύ Νορβηγίας, Ρωσίας και ΕΕ; Και με ποιους τρόπους μπορούν να χρησιμοποιηθούν οι σύγχρονες critical security studies για την υποστήριξη της ανάπτυξης διεθνών πολιτικών που μπορούν να υποστηρίξουν τη βιώσιμη ανάπτυξη στην περιοχή του Barents; Η διατριβή αποτελείται από δέκα κεφάλαια, καθένα από τα οποία ασχολείται με διαφορετικές πτυχές της ανθρωπογεωγραφίας. Το πρώτο κεφάλαιο είναι εισαγωγικό και ορίζει το πλαίσιο της έρευνας. Τα κεφάλαια δύο, τρία και τέσσερα αποτελούν την εκτενή βιβλιογραφική ανασκόπηση, ενώ το πέμπτο κεφάλαιο σκιαγραφεί τη σύγχρονη ιστορία της περιοχής Barents. Οι μεθοδολογικές προσεγγίσεις και η αιτιολόγηση της επιλογής τους παρουσιάζονται στο έκτο κεφάλαιο. Τα κεφάλαια εφτά, οχτώ και εννιά είναι τα κεφάλαια των αποτελεσμάτων, όπου αναλύονται οι critical security studies, ο ρόλος της περιοχής Barents σε θέματα ενεργειακής ασφάλειας της ΕΕ και η περιβαλλοντική και κοινωνική ασφάλεια στην περιοχή του Barents. Τα συμπεράσματα εξάγονται στο δέκατο κεφάλαιο, όπου επιστρέφω σε κάθε ένα από τα ερευνητικά ερωτήματα και συζητώ τη συμβολή της διατριβής μου στην υπάρχουσα εμπειρική γνώση, τις τρέχουσες πολιτικές και πρακτικές.
Current status of insecticide resistance in malaria vectors in the Asian countries: a systematic review
Authors: Susanna Dewi , Pratiwi Dian
Published: January 2022

Background: The application of insecticides for malaria vector control has led to a global problem, which is the current trend of increased resistance against these chemicals. This study aimed to review the insecticide resistance status was previously determined in Asia and how to implement the necessary interventions. Moreover, the implications of resistance in malaria vector control in this region were studied.

Methods: This systematic review was conducted using a predefined protocol based on PRISMA-retrieved articles from four science databases, namely ProQuest, Science Direct, EBSCO, and PubMed in the last ten years (2009 to 2019). The searching process utilized four main combinations of the following keywords: malaria, vector control, insecticide, and Asia. In ProQuest, malaria control, as well as an insecticide, were used as keywords. The following criteria were included in the filter, namely full text, the source of each article, scholarly journal, Asia, and publication date as in the last ten years.

Results: There were 1408 articles retrieved during the initial search (ProQuest=722, Science Direct=267, EBSCO=50, PubMed=285, and Scopus=84). During the screening, 27 articles were excluded because of duplication, 1361 based on title and abstract incompatibility with the inclusion criteria, and 20 due to content differences. In the final screening process, 15 articles were chosen to be analyzed. From the 15 articles, it is known that there was organochlorine (DDT), organophosphate (malathion), and pyrethroids resistance in several Anopheles species with a less than 80% mortality rate.

Conclusion: This review found multiple resistance in several Anopheles includes resistance to pyrethroid. The reports of pyrethroid resistance were quite challenging because it is considered effective in the malaria vector control. Several countries in Asia are implementing an insecticide resistance management (IRM) strategy against malaria vectors following the Global Plan for IRM.
Inhibition of vacuum sublimation artefacts for (Scanning) Transmission Electron Microscopy ((S)TEM) of sulphur samples via encapsulation
Authors: Ronan Oskar , Downing Clive , Nicolosi Valeria
Published: January 2022

Lithium-sulfur battery is one of promising candidates for next-generation energy storage device due to the sulfur cathode material with low cost and nontoxicity, and super high theoretical energy density (nearly 2600Wh kg−1) and specific energy (2567Wh kg−1).

Sulphur, however, poses a few interesting challenges before it can gain widespread utilisation. The biggest issue is known as the polysulphide shuttling effect which contributes to rapid capacity loss after cycling. Accurate characterisation of sulphur cathodic materials becomes critical to our understanding polysulphide shuttling effect in the quest of finding mitigating solutions. Electron microscopy is playing a crucial role in battery research in determining structure–property–function relations. However, sulphur undergoes sublimation at a point above the typical pressures found in the column of a transmission electron microscope (TEM) at room temperature. This makes the imaging and characterisation of any sort of nanostructured sulphur samples challenging, as the material will be modified or even disappear rapidly as soon as it is inserted into the TEM vacuum. As a result, materials characterised by such methods are prone to deviation from normal conditions to a great extent. To prevent this, a novel method of encapsulating sulphur particles between silicon nitride (SiNx) membranes is demonstrated in this work.