Search

The objective of the present study was to detect and quantify aflatoxins in liver and milk of camels. HPLC method was used to detect different aflatoxins. Liver samples were collected from slaughterhouses and milk samples from breeder's sites in Eastern Province, Saudi Arabia. Samples of camel livers and milk (250 samples of each) were collected and analyzed. About 26.4 and 16% of livers showed a contamination level in the range of 0.4-1 ng/g aflatoxin B1 and B2, respectively, but there were no detectable levels of G1, G2, M1 and M2. About 29.7% of milk samples had a range of aflatoxin M1 of 15-50 ng/l and 6% had a range of 50-100 ng/l. However, M2 was not detected in any milk sample. Based on regulatory limits, the present values of aflatoxin in livers and milk were within the internationally accepted limits (permissible limits of aflatoxins are 0.5 ppb for liver and liquid milk, according to the Saudi Organization for Standardization, Meteorology and Quality, (SASO). [ABSTRACT FROM AUTHOR]

Background: Bruton tyrosine kinase inhibitors (BTKis) represent an advancement in chronic lymphocytic leukemia; however, these agents are administered continuously until disease progression or unacceptable toxicity, raising concerns about their affordability. Venetoclax in combination with obinutuzumab (VO) is a fixed-duration (12-month) treatment, approved in Canada in 2020. This study estimated the total cumulative cost of different treatment sequences and evaluated the economic impact of introducing treatment sequences with/without VO, from a Canadian health care system perspective., Methods: A 10-year partitioned survival model was developed, considering key clinical parameters and direct medical costs. Results were stratified by TP53 aberration., Results: Treatment sequences starting with first-line (1L) VO resulted in lower 10-year cumulative costs compared to sequences starting with BTKis administered until disease progression, across both TP53 aberration subgroups. With a maximum of three lines of treatment over a 10-year period, cumulative costs were largely determined by the first two lines of treatment. When comparing sequences with the same 1L treatment, sequences with BTKis in second-line incurred greater costs compared to fixed-duration regimens., Conclusions: Overall, the economic impact of treating all patients with VO led to 10-year cumulative savings of CAD 169,341 and CAD 293,731 per patient, without and with TP53 aberration, respectively. These savings are mainly due to reductions in treatment costs associated with fixed treatment duration.

Beam-like members use corrugated webs to increase their shear strength, stability, and efficiency. The corrugation positively affects the members' structural characteristics, especially those governed by the web parameters, such as the shear strength, while reducing the total weight. Existing code and analytical models for predicting the shear strength of trapezoidal corrugated steel webs (TCSWs) are summarized. This paper presents an optimized Artificial Neural Network (ANN)-based model to estimate the shear strength of steel girders with a TCSW subjected to a concentrated force. A database of 206 experimental results from the literature is used to feed the ANNs. Six geometrical and material parameters were identified as input variables, and the experimental shear strength at failure was considered the output variable. Four hyperparameter optimization techniques are applied to refine the ANN models: Bayesian Optimization (BO), Limited-memory Broyden-Fletcher-Goldfarb-Shanno (L-BFGS), Firefly Algorithm (FA), and African Buffalo Optimization (ABO). The performance metrics indicate that the ABO-ANN model is the most effective among these. The predictions of the developed ML model were also compared with those of existing code and analytical models. The comparisons illustrated that the ANN-based model outperforms the other existing models. The sensitivity analysis using the proposed ANN-based model captured the relationships and interactions among the geometric and material parameters and their impact on shear strength. One main finding is that the corrugation angle in the 35-45° range maximized the TCSW shear strength., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: Informative biomarkers are an urgent need in the management of amyotrophic lateral sclerosis. Serum cardiac troponin T is elevated in the majority of amyotrophic lateral sclerosis patients and increases with disease progression. We sought to establish the informative value of cardiac troponin T with regard to respiratory function, a major prognostic factor in amyotrophic lateral sclerosis., Methods: In this retrospective observation, we analyzed two independent hospital-based cohorts (d = discovery cohort; v = validation cohort) regarding serum cardiac troponin T (n d  = 298; n v  = 49), serum neurofilament light chain (n d  = 117; n v  = 17), and respiratory tests (n d  = 93; n v  = 49)., Results: Serum cardiac troponin T, in contrast to serum neurofilament levels, was associated with the respiratory domain of the revised amyotrophic lateral sclerosis functional rating scale and with pulmonary function parameters, namely forced vital capacity % (r = -0.45, p = 0.001) and slow vital capacity % (r = -0.50, p = 0.001). Serum cardiac troponin T reliably discriminated benchmarks of slow vital capacity <80% (AUC 0.73, 95% CI 0.62-0.84) and <50% (AUC 0.80, 95% CI 0.68-0.93), forced vital capacity <80% (AUC 0.72, 95% CI 0.61-0.83) and <50% (AUC 0.79, 95% CI 0.67-0.91)., Interpretation: Our findings position cardiac Troponin T as a valuable serum biomarker in amyotrophic lateral sclerosis, complementing neurofilaments and expanding the understanding of underlying physiological mechanisms. In clinical practice, serum cardiac troponin T can flag benchmarks of compromised respiratory function., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Suicide is one of the leading causes of death worldwide (WHO, 2021). Depression is a common precursor to suicide and suicidality; however, individuals' experience of depression and the meaning of suicide differs depending on one's cultural background (Colucci, 2013; Goodmann et al., 2021; Kleinman, 2004). The current study explores the relationship between suicide and depression among six broad cultural groups in a large sample (N = 17,015) of adults representing six broad cultural groups (Latin America, South Asia, former Soviet Bloc, Western English-speakers, Chinese, and Arab World). Participants were recruited to a multilingual depression and suicide screening study via Google Ads (Leykin et al., 2012; Gross et al., 2014). As expected, the presence of depression was associated with suicide attempts. However, cultural group moderated this association, with Chinese participants being most likely to report suicide attempts while screening negative for depression. Although depression remains an important predictor of suicidality, it appears that certain cultural groups may be at higher risk even when depression is not present. Clinicians should consider using culturally adapted assessments for depression and suicidality., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Lisdexamfetamine dimesylate (LDX) has demonstrated safety and efficacy for treatment of Binge Eating Disorder (BED). However, to date, trials have not included participants with co-occurring psychiatric disorders. This study explores how LDX affects eating disorder psychopathology, symptoms of common psychiatric comorbidities of BED (ADHD, depression, anxiety), and psychological quality of life, in people with moderate to severe BED., Methods: These are secondary analyses of an open-label LDX trial conducted in 41 adults (18-40 years) over eight-weeks. Participants received LDX titrated to 50 or 70 mg. Clinical assessments and self-report questionnaires were conducted at baseline and 8-week follow-up., Results: Eating disorder psychopathology and psychological quality of life improved after 8-weeks of LDX. No significant group-level changes in depression, anxiety or ADHD severity scores were observed. However, the majority within the small subsets with elevated depression and ADHD symptoms experienced reduced depressive and inattentive symptom severity, respectively., Conclusions: We provide proof-of-concept evidence that LDX may provide broader psychological benefits to individuals with BED, beyond reducing their BE frequency. Effects of LDX on anxiety should be monitored closely by clinicians. Early indications suggest that LDX may be effectively used in people with BED, with and without co-occurring psychiatric conditions, however tolerability may be lower in highly complex cases., Trial Registration: Australian and New Zealand Clinical Trials Registry (anzctr.org.au) #ACTRN12618000623291., (© 2024. The Author(s).)

Background: Self-harm behaviors (performed with either lethal and non-lethal intentions) are common, especially among individuals suffering from mood disorders, and the reasons individuals self-harm vary both by person and by the type of behavior. Understanding these variations may help clinicians determine levels of risk more accurately., Aims: To understand whether culture and gender are associated with the likelihood of engaging in specific self-harm behaviors and whether the intention (lethal, ambivalent, non-lethal) of these behaviors vary with culture and gender., Methods: 2826 individuals took part in an international multilingual online depression/suicidality screening study and reported at least one instance of self-harm in the past year. Participants were grouped into six broad cultural categories (Latin America, South Asia, Russian, Western English, Chinese, Arab)., Results: 3-way (culture x gender x intent) interactions were observed for several self-harm behaviors (overdosing, self-burning, asphyxiating, poisoning, and jumping from heights), suggesting that individuals engage in each of these behaviors with different intentions depending on gender and culture. Cultures and genders likewise differed in the likelihood of engaging in several self-harm behaviors., Conclusions: Clinicians should consider culture and gender when assessing for suicide risk, as similar self-harming behaviors may reflect different intentions depending on an individual's culture and gender.

Zinc Finger DNA-binding domain-containing proteins are the most populous family among eukaryotic transcription factors. Among these, members of the BTB domain-containing ZBTB sub-family are mostly known for their transcriptional repressive functions. In this Viewpoint article, we explore molecular mechanisms that potentially diversify the function of ZBTB proteins based on their homo and heterodimerization, alternative splicing and post-translational modifications. We describe how the BTB domain is as much a scaffold for the assembly of co-repressors, as a domain that regulates protein stability. We highlight another mechanism that regulates ZBTB protein stability: phosphorylation in the zinc finger domain. We explore the non-transcriptional, structural roles of ZBTB proteins and highlight novel findings that describe the ability of ZBTB proteins to associate with poly adenosine ribose in the nucleus during the DNA damage response. Herein, we discuss the contribution of BTB domain scaffolds to the formation of transcriptional repressive complexes, to chromosome compartmentalization and their non-transcriptional, purely structural functions in the nucleus., (© 2023 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Introduction: Self-directed dieting (i.e., unsupervised) is very common among adolescents and young adults but has had almost no direct research. This paper describes the protocol for the My Diet Study, a two-arm observational investigation of the natural progression of dieting among young people over a period of 6-months. The study aims to examine the links between self-directed dieting, general physiological and psychological metrics of wellbeing (e.g., depressive symptoms) and biomarkers of gut-brain axis functions (e.g., microbiome and hormones) that are predicted to influence diet adherence through appetite, mood and metabolism regulation., Methods: Young people aged 16-25, intending to start a diet will be invited to participate in this observational study. For Part 1 (psychological arm), participants will be asked to complete a set of questionnaires and diaries at the beginning of every month for 6 months, to assess overall mental (e.g., psychological distress, disordered eating) and physical (e.g., weight) health, perceived diet success, food intake and gastrointestinal movements. For Part 2 (biological arm), a subsample of 50 participants will be asked to provide feces, blood and saliva for bio-sampling each month for the first 3-months of their participation in Part 1., Discussion: The My Diet Study will be the first longitudinal, observational study of dieting in young people combining in-depth psychological and biological data. It is anticipated that the findings will yield psychological & biological information about the impacts and effectiveness of self-directed dieting in young people, inform a framework for advice on safety in dieting among young people and help to establish the potential for biomarkers for risk management and improvement of diet-based lifestyle interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Okada, Pehlivan, Miskovic-Wheatley, Barakat, Griffiths, Touyz, Simpson, Maguire and Holmes.)

Background: Health and Wellness Coaching (HWC) may be beneficial in chronic condition care. We sought to appraise its effectiveness on quality of life (QoL), self-efficacy (SE), depression, and anxiety., Methods: We searched MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane CENTRAL for randomized trials published January 2005 - March 2023 that compared HWC to standard clinical care or another intervention without coaching. We examined QoL, SE, depression, or anxiety outcomes. Meta-analysis utilizing the random-effects model was used to estimate the pooled standardized mean difference (SMD)., Results: Thirty included studies demonstrated that HWC improved QoL within 3 months (SMD 0.62 95 % CI 0.22-1.02, p = 0.002), SE within 1.5 months (SMD 0.38, 95 % CI 0.03-0.73, p = 0.03), and depression at 3, 6, and 12 months (SMD 0.67, 95 % CI 0.13-1.20, p = 0.01), (SMD 0.72, 95 % CI 0.19-1.24, p = 0.006), and (SMD 0.41, 95 % CI 0.09-0.73, p = 0.01) Certainty in the evidence for most outcomes was either very low or low primarily due to the high risk of bias, heterogeneity, and imprecision., Conclusion: HWC improves QoL, SE, and depression across chronic illness populations. Future research needs to standardize intervention reporting and outcome collection., Practice Implications: Future HWC studies should standardize intervention components, reporting, and outcome measures, apply relevant chronic illness theories, and aim to follow participants for greater than one year., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

High dropout rates and poor adherence associated with digital interventions have prompted research into modifications of these treatments to improve engagement and completion rates. This trial aimed to investigate the added benefit of clinician support when paired alongside a ten-session, online cognitive behaviour therapy (CBT) self-help intervention for bulimia nervosa (BN). As part of a three-arm, phase II randomised controlled trial, 114 participants (16 years or over) with full or subthreshold BN were randomly assigned to complete the intervention in a self-help mode (with administrative researcher contact; n = 38), with adjunct clinician support (weekly 30-minute videoconferencing sessions; n = 37), or a no-treatment waitlist control (WLC; n = 39). Baseline to post-treatment (12-weeks) decreases in objective binge episode frequency were significantly greater for clinician-supported participants as compared to WLC, but not for self-help when compared to WLC. However, due to continued improvements for self-help across follow-up (24-weeks), both arms outperformed WLC when analysed as an overall rate of change across three timepoints. Clinician-supported participants outperformed self-help in regards to laxative use and dietary restraint. Our results demonstrate that good clinical outcomes can be achieved with a relatively brief online CBT-based program even in the absence of structured clinical support, indicating a possible overreliance upon clinician support as a primary adherence-facilitating mechanism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Studies in transdiagnostic eating disorder (ED) samples suggest supported online self-help programs (eTherapies) are effective and may improve access to treatment; however, their evaluation in those with binge-eating disorder (BED) is limited. Given BED's high prevalence and low levels of treatment uptake, further eTherapy evaluation is needed to broaden access to effective, evidence-based treatment options. The aim of this study was to investigate the acceptability, feasibility, and preliminary efficacy of a supported eTherapy for those with BED or subthreshold BED, and to examine symptom change across the duration of therapy., Method: Nineteen women with BED completed a supported, 10-session Cognitive Behavioural Therapy-based eTherapy in an uncontrolled, pre-post, and 3 months follow up intervention study. Key outcomes were assessed by the Eating Disorder Examination Questionnaire (EDE-Q): objective binge episode (OBE) frequency and ED psychopathology. Feasibility was evaluated via program adherence and dropout, whilst acceptability was assessed through participant feedback post-treatment. Weekly symptom change (ED psychopathology) during treatment was assessed by the Eating Disorder Examination - Questionnaire Short (EDE-QS)., Results: Generalised estimating equations showed statistically and clinically significant reductions in OBEs and ED psychopathology (large effects) post-treatment, with these decreases maintained at follow up. Across weekly assessment, a marked slowing in the rate of change in ED psychopathology was observed after four sessions of the program. Program feasibility was high (i.e., 84% of content completed), as was program acceptability (i.e., 93% of participants expressed high levels of satisfaction)., Discussion: These results support the acceptability, feasibility, and preliminary efficacy of a supported eTherapy program for those with BED and suggest the variability of symptom change across the duration of therapy. Future research should further investigate findings in an adequately powered randomised controlled trial., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rom, Miskovic-Wheatley, Barakat, Aouad, Kim, Fuller-Tyszkiewicz and Maguire.)

Suicide in the Arab World is grossly understudied. This study sought to understand suicidality among Arabic-speaking individuals visiting an online depression screener. A large sample (N = 23,201) from the Arab World was recruited online. 78.9% (n = 17,042) reported suicidality (thoughts of death or suicide, or a suicide attempt) and 12.4% reported a suicide attempt in the past 2 weeks. Binary logistic regressions indicated that women tended to report more suicidality, and that suicidality tended to decline with age (all ps < 0.001), across all levels of suicidality. Comparing countries with n ≥ 1000 (Algeria, Egypt, Jordan, Morocco, and Saudi Arabia), several 3-way (gender * age * country) and 2-way interactions indicated that some countries departed from the usual pattern of responses. For instance, in Algeria, neither gender nor age differences were observed in reported attempts. Women and younger adults in the Arab World may be at higher risk of suicidality. Differences between and within countries warrant further exploration., (© 2023. The Author(s).)

Background: The development of sequencing technology increases the number of genomes being sequenced. However, obtaining a quality genome sequence remains a challenge in genome assembly by assembling a massive number of short strings (reads) with the presence of repetitive sequences (repeats). Computer algorithms for genome assembly construct the entire genome from reads in two approaches. The de novo approach concatenates the reads based on the exact match between their suffix-prefix (overlapping). Reference-guided approach orders the reads based on their offsets in a well-known reference genome (reads alignment). The presence of repeats extends the technical ambiguity, making the algorithm unable to distinguish the reads resulting in misassembly and affecting the assembly approach accuracy. On the other hand, the massive number of reads causes a big assembly performance challenge., Method: The repeat identification method was introduced for misassembly by prior identification of repetitive sequences, creating a repeat knowledge base to reduce ambiguity during the assembly process, thus enhancing the accuracy of the assembled genome. Also, hybridization between assembly approaches resulted in a lower misassembly degree with the aid of the reference genome. The assembly performance is optimized through data structure indexing and parallelization. This article's primary aim and contribution are to support the researchers through an extensive review to ease other researchers' search for genome assembly studies. The study also, highlighted the most recent developments and limitations in genome assembly accuracy and performance optimization., Results: Our findings show the limitations of the repeat identification methods available, which only allow to detect of specific lengths of the repeat, and may not perform well when various types of repeats are present in a genome. We also found that most of the hybrid assembly approaches, either starting with de novo or reference-guided, have some limitations in handling repetitive sequences as it is more computationally costly and time intensive. Although the hybrid approach was found to outperform individual assembly approaches, optimizing its performance remains a challenge. Also, the usage of parallelization in overlapping and reads alignment for genome assembly is yet to be fully implemented in the hybrid assembly approach., Conclusion: We suggest combining multiple repeat identification methods to enhance the accuracy of identifying the repeats as an initial step to the hybrid assembly approach and combining genome indexing with parallelization for better optimization of its performance., Competing Interests: The authors declare there are no competing interests., (©2023 Magdy Mohamed Abdelaziz Barakat et al.)

Background: The aim of this systematic review is to identify cases of neurogenic ocular palsy in the presence of COVID-19 and to document patient characteristics, type of palsy and possible aetiologies., Methods: A systematic search of PubMed, Medline and CINAHL databases was conducted on the 6th of January 2023 to identify cases of neurogenic ocular palsy in patients with current or previous COVID-19 infection. Data were pooled to summarise the neurogenic palsy, patient clinical characteristics and proposed palsy mechanisms., Results: The combined database search yielded 1197 articles. Of these, 23 publications consisting of 25 patients met the inclusion criteria. Most patients were male (68%) and ranged in age from 2 to 71 years (median=32.7, SD=21.4). Seven patients (28%) were children aged 2 to 10 years old. Abducens palsies were most common (68%) and the most common ocular presentation was diplopia (76%) with an average time of onset 15 days from testing positive to COVID-19 or having symptoms of the virus. Proposed mechanism of development of a neurogenic palsy secondary to COVID-19 infection was classified into one of three categories: vascular/thrombotic, a viral neuro-invasive or inflammatory virus-mediated immune response., Discussion: This study suggests that COVID-19 infection may be linked to oculomotor, trochlear and abducens nerve palsies and the underlying mechanisms may vary but are difficult to definitively establish. Further studies investigating the onset of neurogenic palsy secondary to COVID-19 infection is required.

Background: Venetoclax is a first-in-class targeted therapy option that is an inducer of apoptosis in chronic lymphocytic leukemia (CLL) cells. The open-label phase III CLL14 clinical trial showed that venetoclax combined with obinutuzumab (VEN+O) is superior to obinutuzumab combined with chlorambucil in newly diagnosed patients with CLL. The aim of this study was to assess the health economic value of VEN+O for the frontline treatment of CLL in Canada from a publicly funded healthcare system perspective., Methods: A partitioned survival analyses model was developed including three health states: progression free, progressed, and death. A cycle length of 28 days and a time horizon of 10 years was assumed. VEN+O treatment for a fixed duration of 12 months was compared to obinutuzumab combined with chlorambucil, fludarabine plus cyclophosphamide plus rituximab, bendamustine plus rituximab, chlorambucil plus rituximab, ibrutinib, and acalabrutinib. The population in the model included both unfit and overall frontline CLL patients, two subgroups were also assessed (patients with del17p/TP53 mutations and patients without del17p/TP53 mutations). Survival data extrapolated from the CLL14 trial were used to populate the model. Uncertainty was assessed via one-way sensitivity analyses, probabilistic analyses, and scenario analyses., Results: Based on the probabilistic analyses, unfit frontline CLL patients receiving VEN+O were estimated to incur costs of Canadian dollars ($) 217,727 [confidence interval (CI) $170,725, $300,761] (del17p/TP53: $209,102 [CI $159,698, $386,190], non-del17p/TP53: $217,732 [CI $171,232, $299,063]) and accrue 4.96 [CI 4.04, 5.82] quality-adjusted life-years (del17p/TP53: 3.11 [CI 2.00, 4.20], non-del17p/TP53: 5.04 [CI 4.05, 5.92]). Obinutuzumab combined with chlorambucil, bendamustine plus rituximab, chlorambucil plus rituximab, and ibrutinib accrued lower quality-adjusted life-years and higher costs and as such, VEN+O was the dominant treatment option. The full incremental analysis showed that acalabrutinib was more expensive and more efficacious compared with VEN+O with an incremental-cost-effectiveness-ratio of $2,139,180/quality-adjusted life-year versus VEN+O and not a cost-effective option in Canada. Probabilistic analyses show that at a willingness to pay of $50,000/quality-adjusted life-year gained, VEN+O has the greatest probability of being cost effective., Conclusions: VEN+O is a cost-effective treatment option for unfit frontline CLL patients and provides value for money to healthcare payers., (© 2022. The Author(s).)

University of California Health (UCH) provided a system-wide, rapid response to the humanitarian crisis of unaccompanied children crossing the southern U.S. border in the midst of the COVID-19 pandemic in 2021. In collaboration with multiple federal, state, and local agencies, UCH mobilized a multidisciplinary team to deliver acute general and specialty pediatric care to unaccompanied children at 2 Californian emergency intake sites (EISs). The response, which did not disrupt normal UCH operations, mobilized the capacities of the system and resulted in a safe and developmentally appropriate environment that supported the physical and mental health of migrant children during this traumatic period. The capacities of UCH's 6 academic health centers ensured access to trauma-informed medical care and culturally sensitive psychological and social support. Child life professionals provided access to exercise, play, and entertainment. Overall, 260 physicians, 42 residents and fellows, 4 nurse practitioners participated as treating clinicians and were supported by hundreds of staff across the 2 EISs. Over 5 months and across both EISs, a total of 4,911 children aged 3 to 17 years were cared for. A total of 782 children had COVID-19, most infected before arrival. Most children (3,931) were reunified with family or sponsors. Continuity of care after reunification or placement in a long-term shelter was enhanced by use of an electronic health record. The effort provided an educational experience for residents and fellows with instruction in immigrant health and trauma-informed care. The effort benefitted from UCH's recent experience of providing a system-wide response to the COVID-19 pandemic. Lessons learned are reported to encourage the alignment and integration of academic health centers' capacities with federal, state, and local plans to better prepare for and respond to the accelerating need to care for those in the wake of disasters and humanitarian crises., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Association of American Medical Colleges.)

Background: Risk factors represent a range of complex variables associated with the onset, development, and course of eating disorders. Understanding these risk factors is vital for the refinement of aetiological models, which may inform the development of targeted, evidence-based prevention, early intervention, and treatment programs. This Rapid Review aimed to identify and summarise research studies conducted within the last 12 years, focusing on risk factors associated with eating disorders., Methods: The current review forms part of a series of Rapid Reviews to be published in a special issue in the Journal of Eating Disorders, funded by the Australian Government to inform the development of the National Eating Disorder Research and Translation Strategy 2021-2031. Three databases were searched for studies published between 2009 and 2021, published in English, and comprising high-level evidence studies (meta-analyses, systematic reviews, moderately sized randomised controlled studies, moderately sized controlled-cohort studies, or population studies). Data pertaining to risk factors for eating disorders were synthesised and outlined in the current paper., Results: A total of 284 studies were included. The findings were divided into nine main categories: (1) genetics, (2) gastrointestinal microbiota and autoimmune reactions, (3) childhood and early adolescent exposures, (4) personality traits and comorbid mental health conditions, (5) gender, (6) socio-economic status, (7) ethnic minority, (8) body image and social influence, and (9) elite sports. A substantial amount of research exists supporting the role of inherited genetic risk in the development of eating disorders, with biological risk factors, such as the role of gut microbiota in dysregulation of appetite, an area of emerging evidence. Abuse, trauma and childhood obesity are strongly linked to eating disorders, however less conclusive evidence exists regarding developmental factors such as role of in-utero exposure to hormones. Comorbidities between eating disorders and mental health disorders, including personality and mood disorders, have been found to increase the severity of eating disorder symptomatology. Higher education attainment, body image-related factors, and use of appearance-focused social media are also associated with increased risk of eating disorder symptoms., Conclusion: Eating disorders are associated with multiple risk factors. An extensive amount of research has been conducted in the field; however, further studies are required to assess the causal nature of the risk factors identified in the current review. This will assist in understanding the sequelae of eating disorder development and in turn allow for enhancement of existing interventions and ultimately improved outcomes for individuals., (© 2022. The Author(s).)

Background: When screening for suicidality, clinicians usually ask questions in ascending order of severity. Clinicians often discontinue questioning after negative responses to the first question or questions, presuming that these individuals are unlikely to endorse any further suicidality. In this study, the accuracy of this presumption is evaluated in a large international sample., Methods: Participants were 21,385 individuals reporting a suicide attempt in the past two weeks. Participants were recruited, primarily via Google Ads, to a quintilingual (English, Spanish, Chinese, Arabic, and Russian) multinational depression and suicide screening study., Results: Examining three initial screening questions (i.e., thoughts of death, wanting to die, and thinking about committing suicide), 14.8 % (n = 3179) of participants denied one or more question, 3.96 % (n = 847) denied two, and 1.95 % (n = 416) denied all three questions. The proportions of individuals with discrepant responses differed between linguistic-geographical groups, with Chinese and South Asian groups being more likely to be discrepant across all questions (all ps < .001)., Limitations: Suicidality was assessed using an internet-based self-report measure, and linguistic-geographical groups explored in this study are very broad, which may limit generalizability., Conclusions: Results suggest that prematurely discontinuing suicide screening may fail to capture some individuals who made a recent attempt, and that in some groups, this discrepancy may be more pronounced. Clinicians should assess all individuals as thoroughly as possible regardless of initial responses, inquire about other significant risk factors, and be culturally sensitive., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: As innovative oncology medicines are rapidly developed, there is increasing pressure on payers to offer patients timely access to life-saving therapies. The uncertainty surrounding these therapies when phase III clinical trials are pending has necessitated new, adapted pathways to market access, with timelines that greatly vary by country. Understanding differences between pathways may identify opportunities to expedite patient access universally., Objectives: To describe early access pathways for new oncology medicines among selected countries with established health technology assessment (HTA) frameworks and publicly funded health systems, with a special focus on real-world evidence (RWE)., Methods: We reviewed the HTA agency websites of the selected OECD countries: National Institute for Health and Care Excellence (NICE) for England and Wales; Haute Autorité de Santé (HAS) for France; IQWiG and G-BA for Germany; Agenzia Italiana del Farmaco (AIFA) for Italy; Pharmaceutical Benefits Advisory Committee (PBAC) for Australia; and CADTH and Institut National d'Excellence en Santé et Services Sociaux (INESSS) for Canada as the primary source of evidence., Results: Processes for early patient access to innovative oncology therapies varied across selected countries; however, most countries have an established pathway for publicly funded early access (England and Wales, France, Germany, Italy, and Australia). The utilization of RWE to support earlier access (coverage with evidence) also varied by country, with some HTA organizations being actively engaged in these agreements (NICE, AIFA, and HAS) and others having no established processes in place (G-BA and CADTH/INESSS)., Conclusions: This review of early access pathways for novel oncology medicines found substantial variability between countries of interest. Coverage with evidence frameworks may provide a unique opportunity for industry and payers to collaborate on earlier access to innovative cancer therapies with life-saving potential.

Bulimia nervosa is an eating disorder characterised by marked impairment to one's physical health and social functioning, as well as high rates of chronicity and comorbidity. This literature review aims to summarise existing academic research related to the symptom profile of BN, the costs and burden imposed by the illness, barriers to the receipt of care, and the evidence base for available psychological treatments. As a consequence of well-documented difficulties in accessing evidence-based treatments for eating disorders, efforts have been made towards developing innovative, diverse channels to deliver treatment, with several of these attempting to harness the potential of digital platforms. In response to the increasing number of trials investigating the utility of online treatments, this paper provides a critical review of previous attempts to examine digital interventions in the treatment of eating disorders. The results of a focused literature review are presented, including a detailed synthesis of a knowledgeable selection of high-quality articles with the aim of providing an update on the current state of research in the field. The results of the review highlight the potential for online self-help treatments to produce moderately sized reductions in core behavioural and cognitive symptoms of eating disorders. However, concern is raised regarding the methodological limitations of previous research in the field, as well as the high rates of dropout and poor adherence reported across most studies. The review suggests directions for future research, including the need to replicate previous findings using rigorous study design and methodology, as well as further investigation regarding the utility of clinician support and interactive digital features as potential mechanisms for offsetting low rates of engagement with online treatments.

Objective: For those with binge-eating disorder (BED), access to evidence-based, face-to-face treatment is often constrained by clinician availability and high treatment costs. Emerging evidence suggests online therapy (eTherapy) may navigate these barriers and reduce binge-eating symptomatology; however, less evaluation has been done in those with BED, particularly with briefer programs targeting early change. This study investigated the feasibility and potential efficacy of a brief, supported eTherapy in those with BED or subthreshold BED., Method: Participants were 19 women with BED who completed a four-session eTherapy. This was a single-arm, pre-post intervention study, with participants completing weekly content and attending telehealth sessions. Key outcomes were assessed by the Eating Disorder Examination Questionnaire-Short (EDE-QS): objective binge episode days, loss of control over eating days, and eating disorder (ED) psychopathology via a total EDE-QS score., Results: Generalized and linear mixed models showed significantly reduced loss of control over eating days and ED psychopathology. Program feasibility was high, with strong program adherence and a below average attrition rate., Discussion: Pilot results support the feasibility and potential efficacy of a brief, behavioral-focused eTherapy program in reducing ED pathology in those with BED. Future research should further investigate findings in an adequately powered randomized controlled trial., Public Significance: This study suggests that a brief, behavioral-focused online therapy, guided by non-expert clinicians, can be successfully administered to those with binge-eating disorder (BED) and may be efficacious at reducing eating disorder and other related symptomatology. Brief eTherapies that are effective, accessible, and rapidly available may facilitate earlier intervention in illness and improve treatment outcomes for individuals who experience this common and distressing disorder., (© 2022 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Supervised learning with the restriction of a few existing training samples is called Few-Shot Learning. FSL is a subarea that puts deep learning performance in a gap, as building robust deep networks requires big training data. Using transfer learning in FSL tasks is an acceptable way to avoid the challenge of building new deep models from scratch. Transfer learning methodology considers borrowing the architecture and parameters of a previously trained model on a large-scale dataset and fine-tuning it for low-data target tasks. But practically, fine-tuning pretrained models in target FSL tasks suffers from overfitting. The few existing samples are not enough to correctly adjust the pretrained model's parameters to provide the best fit for the target task. In this study, we consider mitigating the overfitting problem when applying transfer learning in few-shot Handwritten Character Recognition (HCR) tasks. A data augmentation approach based on Conditional Generative Adversarial Networks is introduced. CGAN is a generative model that can create artificial instances that appear more real and indistinguishable from the original samples. CGAN helps generate extra samples that hold the possible variations of human handwriting instead of applying traditional image transformations. These transformations are low-level, data-independent operations, and only produce augmented samples with limited diversity. The introduced approach was evaluated in fine-tuning the three pretrained models: AlexNet, VGG-16, and GoogleNet. The results show that the samples generated by CGAN can enhance transfer learning performance in few-shot HCR tasks. This is by achieving model fine-tuning with fewer epochs and by increasing the model's [Formula: see text] and decreasing the Generalization Error [Formula: see text]., (© 2022. The Author(s).)

The BTB domain is an oligomerization domain found in over 300 proteins encoded in the human genome. In the family of BTB domain and zinc finger-containing (ZBTB) transcription factors, 49 members share the same protein architecture. The N-terminal BTB domain is structurally conserved among the family members and serves as the dimerization site, whereas the C-terminal zinc finger motifs mediate DNA binding. The available BTB domain structures from this family reveal a natural inclination for homodimerization. In this study, we investigated the potential for heterodimer formation in the cellular environment. We selected five BTB homodimers and four heterodimer structures. We performed cell-based binding assays with fluorescent protein-BTB domain fusions to assess dimer formation. We tested the binding of several BTB pairs, and we were able to confirm the heterodimeric physical interaction between the BTB domains of PATZ1 and PATZ2, previously reported only in an interactome mapping experiment. We also found this pair to be co-expressed in several immune system cell types. Finally, we used the available structures of BTB domain dimers and newly constructed models in extended molecular dynamics simulations (500 ns) to understand the energetic determinants of homo- and heterodimer formation. We conclude that heterodimer formation, although frequently described as less preferred than homodimers, is a possible mechanism to increase the combinatorial specificity of this transcription factor family., (© 2022 Piepoli et al.)

We aimed to conduct a systematic review and meta-analysis to compare the efficacy and safety of titrated oral misoprostol versus static oral misoprostol for labour induction. We searched for the available randomised clinical trials (RCTs) in the Cochrane Library, PubMed, ISI web of science, Scopus, and ClinicalTrials.gov. We included RCTs compared titrated oral misoprostol versus static regimen of oral misoprostol during labour induction. Our main outcomes were vaginal and caesarean delivery rates, uterine tachysystole, misoprostol side effects, and neonatal adverse events. Three RCTs met our inclusion criteria with a total number of 360 patients. The vaginal delivery rate did not significantly differ between both groups (p = 0.49). Titrated oral misoprostol was associated with significant increase in the caesarean delivery rate compared to static oral misoprostol (p = 0.04). Moreover, titrated oral misoprostol led to significant increase in the uterine tachysystole and misoprostol side effects (p = 0.01 & p = 0.003, respectively). There were no differences among both groups regarding different neonatal adverse events. In conclusion, titrated oral misoprostol increases the incidence of caesarean delivery, uterine tachysystole, and misoprostol side effects with a similar vaginal delivery rate compared to static dose misoprostol. Thus, static oral misoprostol should be used instead of titrated oral misoprostol during labour induction. Impact Statement What is already known on this subject? Different studies have evaluated titrated oral misoprostol administration for induction of labour and proved their efficacy in comparison with other induction methods. However, there is controversy among the published studies between titrated oral misoprostol and static oral misoprostol during induction of labour. A recent study concluded that hourly titrated misoprostol and static oral misoprostol are equally safe and effective when utilised for induction of labour with no fear of any adverse events. However, another study recommended static oral misoprostol administration for labour induction as it was linked to a lower caesarean section incidence, fewer drug side effects, and decline in complication rates in comparison with titrated oral misoprostol. What the results of this study add? Titrated oral misoprostol increases the incidence of caesarean delivery, uterine tachysystole, and misoprostol side effects with a similar vaginal delivery rate compared to static dose misoprostol. What the implications are of these findings for clinical practice and/or further research? Static oral misoprostol should be used instead of titrated oral misoprostol during labour induction. More future trials are required to confirm our findings.

Diabetic retinopathy (DR) is a serious disease that may cause vision loss unawares without any alarm. Therefore, it is essential to scan and audit the DR progress continuously. In this respect, deep learning techniques achieved great success in medical image analysis. Deep convolution neural network (CNN) architectures are widely used in multi-label (ML) classification. It helps in diagnosing normal and various DR grades: mild, moderate, and severe non-proliferative DR (NPDR) and proliferative DR (PDR). DR grades are formulated by appearing multiple DR lesions simultaneously on the color retinal fundus images. Many lesion types have various features that are difficult to segment and distinguished by utilizing conventional and hand-crafted methods. Therefore, the practical solution is to utilize an effective CNN model. In this paper, we present a novel hybrid, deep learning technique, which is called E-DenseNet. We integrated EyeNet and DenseNet models based on transfer learning. We customized the traditional EyeNet by inserting the dense blocks and optimized the resulting hybrid E-DensNet model's hyperparameters. The proposed system based on the E-DenseNet model can accurately diagnose healthy and different DR grades from various small and large ML color fundus images. We trained and tested our model on four different datasets that were published from 2006 to 2019. The proposed system achieved an average accuracy (ACC), sensitivity (SEN), specificity (SPE), Dice similarity coefficient (DSC), the quadratic Kappa score (QKS), and the calculation time (T) in minutes (m) equal [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], 0.883, and 3.5m respectively. The experiments show promising results as compared with other systems., (© 2022. The Author(s).)

This study investigated the concrete-to-concrete friction behavior under dynamic cyclic loading at different loading rates, vertical loads, and surface roughness. The present work answers essential questions about the dynamic behavior of concrete-to-concrete friction since most of the available literature deals with static or quasi-static loading conditions. To this end, an experimental program was devised by casting 96 concrete blocks. A total of 48 dynamic push-pull tests were performed on each pair of blocks (mobile top block and fixed bottom block). Test variables included three types of surface roughness, four different loading rates, and two normal stresses. Performance measures included the static and dynamic friction forces coefficients of static and kinetic friction in addition to effective stiffness and effective damping. Moreover, the test results showed that the static and kinetic friction coefficients, effective stiffness, and effective damping decrease with increasing loading rates. Moreover, increasing the normal stress increases the friction force, thus increasing the effective stiffness and reducing the effective damping surface for all surface roughness types. The effects of test variables on the hysteresis behavior were also investigated., (© 2022. The Author(s).)

Background: Repeated high-dose methotrexate (HDMTX) is a critical component of contemporary childhood acute lymphoblastic leukemia (ALL) treatment regimens. Serum albumin is considered a carrier of methotrexate (MTX) in the blood. Hypoalbuminemia is not a rare finding in children with leukemia. This study aimed to investigate the relationship between pre-infusion serum albumin and possible HDMTX toxicities., Methods: Thirty Egyptian children with ALL were consecutively enrolled in the study between May 2018 and July 2020. They were prospectively followed up while receiving HDMTX during the consolidation phase of the TOTAL study XV protocol. HDMTX was administered intravenously as a 24-h infusion every 2 weeks. Doses of 2.5 g/m 2 were used for low-risk patients and 5 g/m 2 for standard/high-risk patients. The Common Terminology Criteria for Adverse Events (V.4.03) was used to report the observed toxicities after HDMTX cycles. Plasma MTX levels were estimated at 24 h (MTX 24 ) from the beginning of HDMTX infusion in the first consolidation cycle. Serum albumin level was determined before HDMTX administration, and pre-infusion hypoalbuminemia was defined when serum albumin was <3.5 g/dL., Results: The patients' age ranged from 2.3 to 13.3 years at diagnosis, and most of them had B cell ALL (86.7%). Overall, 120 HDMTX cycles were analyzed, equally distributed between low and standard/high risk. Grade 3-4 anemia, grades 3-4 thrombocytopenia, febrile neutropenia, and oral mucositis were significantly more frequent in HDMTX cycles with pre-infusion hypoalbuminemia than those with normal pre-infusion albumin (p=0.003, p=0.007, p=0.006, and p=0.001, respectively). In addition, pre-infusion hypoalbuminemia was significantly associated with additional hospitalization due to HDMTX toxicity (p=0.031). Most HDMTX toxicities were comparable irrespective of the MTX dose. Oral mucositis was more frequently encountered in the 2.5 g/m 2 than the 5 g/m 2 HDMTX cycles (46.7 vs. 26.7%, p=0.023). A significantly longer hospitalization (due to HDMTX toxicity) was observed in the 5 g/m 2 HDMTX cycles (median= 7 days vs. 4 days, p=0.012)., Conclusions: Serum albumin levels should be checked before starting HDMTX cycles, especially in resource-limited settings where malnutrition is common, and serum MTX monitoring may not be available. Optimizing serum albumin levels before HDMTX may help decrease the possibility of HDMTX toxicities., (© 2022. The Author(s).)

Camelidae derived single-domain antibodies (sdAbs), commonly known as nanobodies (Nbs), are the smallest antibody fragments with full antigen-binding capacity. Owing to their desirable properties such as small size, high specificity, strong affinity, excellent stability, and modularity, nanobodies are on their way to overtake conventional antibodies in terms of popularity. To date, a broad range of nanobodies have been generated against different molecular targets with applications spanning basic research, diagnostics, and therapeutics. In the field of molecular imaging, nanobody-based probes have emerged as a powerful tool. Radioactive or fluorescently labeled nanobodies are now used to detect and track many targets in different biological systems using imaging techniques. In this review, we provide an overview of the use of nanobodies as molecular probes. Additionally, we discuss current techniques for the generation, conjugation, and intracellular delivery of nanobodies., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction This research, through the analysis of the case-law of the Inter-American Court of Human Rights (IACtHR), seeks to shed light on the nexus between families of the missing' claims, their agency and State compliance with reparations. The IACtHR has a unique follow-up system in the area of reparations, where victims can directly address the judges during hearings. This paper suggests that victims' participation - before and after the judgment- pervades the legal rigidity of international jurisdictions and contributes to a better understanding of reparations., Introduction: The number of forcibly displaced immigrants seeking asylum in the United States continues to rapidly increase. Movement from Latin America to the United States was the third-largest migration worldwide in 2017 (Leyva-Flores et al., 2019). As migration patterns change, understanding the background and trauma profile of newly displaced populations is essential to meet their health needs and aid successful resettlement. University-affiliated student-run asylum clinics conduct a growing number of forensic medical evaluations of asylum seekers and provide a vital lens to study changes in this population's profile over time., Methods: A retrospective review was conducted of the first 102 asylum seekers receiving forensic medical evaluations between 2019 and 2021 at a university-affiliated student- run clinic, reporting demographics; trauma, medical, and mental health histories; referral patterns; and legal outcomes. Bivariate statistics were used to investigate the relationship between past trauma and mental health outcomes., Results: Clients reported an average of 4.4 different types of physical, psychological, and sexual ill-treatment per person. The current mental health burden was extensive with 86.9 percent of clients reporting symptoms of PTSD and/or depression. Clinician-student teams evaluated clients within a clinic structure deploying a continuous improvement model to reduce common barriers to forensic evaluations and promote longitudinal follow- up and referrals., Discussion: This study demonstrates the complexity of trauma exposure reported by asylum seekers, contributes to the evidence on how trauma results in mental health outcomes, and describes trauma-centred clinic adaptations that reduce barriers to forensic evaluations known to improve the rates of legal protection.