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Introduction: Bullying, a severe form of mistreatment, occurs when an individual in an authority position intentionally imposes negative persistent behaviors on a target. In academic medicine, bullying is used to impede the target's professional growth. While there is abundant literature on how to disrupt other forms of mistreatment, the literature related to bullying among academic medical faculty members is scarce., Methods: We developed an interactive workshop on disrupting faculty-on-faculty bullying in academic medicine, with a focus on gender-based bullying, following Kern's model of curriculum development. The workshop consisted of three didactics on the scope of bullying in academic medicine: identifying bullying behaviors, learning strategies to mitigate bullying, and understanding what constitutes comprehensive antibullying policies. The workshop also included three small-group activities to reinforce learned concepts., Results: Eighty-seven faculty attended one of three workshops held over a 6-month period. We received 24 completed evaluations for a 28% rate of return. Most participants rated workshop activities as being well taught and of great value. Many respondents commented that after participating in the workshop, they realized they had likely experienced or witnessed bullying in their careers and that mitigating bullying required effort at multiple levels (individual, institutional, national)., Discussion: This workshop fills a need in academic medicine through addressing how faculty members and institutions can help themselves and others to disrupt bullying. We will continue to disseminate this workshop at national conferences and at individual institutions. This resource will allow other educators to offer the workshop at their home institutions., (© 2023 Iyer et al.)

Antibody engineering has developed into a wide-reaching field, impacting a multitude of industries, most notably healthcare and diagnostics. The seminal work on developing the first monoclonal antibody four decades ago has witnessed exponential growth in the last 10-15 years, where regulators have approved monoclonal antibodies as therapeutics and for several diagnostic applications, including the remarkable attention it garnered during the pandemic. In recent years, antibodies have become the fastest-growing class of biological drugs approved for the treatment of a wide range of diseases, from cancer to autoimmune conditions. This review discusses the field of therapeutic antibodies as it stands today. It summarizes and outlines the clinical relevance and application of therapeutic antibodies in treating a landscape of diseases in different disciplines of medicine. It discusses the nomenclature, various approaches to antibody therapies, and the evolution of antibody therapeutics. It also discusses the risk profile and adverse immune reactions associated with the antibodies and sheds light on future applications and perspectives in antibody drug discovery.

Despite progress made over the past decade, women are under-represented in positions of leadership in academic medicine. Women physicians face numerous challenges throughout their careers. Despite achieving leadership positions, women in leadership continue to experience the impact of those challenges. In this review, we describe four misconceptions about women in leadership, along with their impact and recommendations. First, we describe differences between mentorship and sponsorship, as well as their impact on attaining leadership positions. Second, the gender pay gap persists throughout women's careers, regardless of leadership positions. Third, we explore the role of self-efficacy in leadership in the context of stereotype threats. Fourth, gendered expectations of leadership characteristics place an undue burden on women, detracting from their leadership effectiveness. Organizations can address the challenges women face by creating robust mentorship and sponsorship networks, establishing transparent and equitable pay policies, promoting and normalizing a broader range of leadership styles, and improving work flexibility and support structure. Ultimately, such changes serve all members of the organization through increased retention and engagement., (© 2023. Canadian Anesthesiologists' Society.)

Background: Bullying has been identified as a problem in the academic medicine. Bullying behaviors persist because organizational cultures have allowed them to become normalized. In academic medicine, women are more likely to be bullied than men. Our purpose was to explain why gender-based bullying persists in academic medicine and identify mitigation strategies. Methods: We interviewed senior faculty women physicians who graduated from the Hedwig van Ameringen Executive Leadership in Academic Medicine ® program. We asked participants about their experience with bullying and its consequence on their careers. We also asked about the types of culture they think perpetuates bullying and their thoughts on how best to mitigate bullying. Interviews were recorded, transcribed, and coded using Averbuch's Cycle of Academic Bullying as a framework. Results: We sampled 30 women physician leaders for interviews from a pool of 96 volunteers who had screened positive for experiencing bullying. All 30 either experienced or witnessed bullying during their careers. Bullying behaviors included public humiliation, defamation, verbal disparagement, and social isolation. Subjects suffered numerous negative effects from bullying such as stress, burnout, depression, and having to leave the job. Participants believed bullying behaviors persisted due to hierarchical organizational cultures. Barriers to reporting and mitigation were thought to originate from lack of leadership combined with ineffective policies and reporting mechanisms. Conclusions: Dysfunctional hierarchies embedded in organizational cultures within academic medicine have contributed to the normalization of bullying. Committed leadership, focused on implementing comprehensive bullying prevention policies, is needed to promote an inclusive culture in which everyone feels that they belong.

Importance: Closing the diversity gap is critical to ensure equity in medical education and health care quality. Nevertheless, evidence-based strategies and best practices to improve diversity, equity, and inclusion (DEI) in the biomedical workforce remain poorly understood and underused. To improve the culture of DEI in graduate medical education (GME), in 2020 the Accreditation Council of Graduate Medical Education (ACGME) launched the Barbara Ross-Lee, DO, Diversity, Equity, and Inclusion Award to recognize exceptional DEI efforts in US residency programs., Objective: To identify strategies and best practices that exemplary US GME programs use to improve DEI., Design and Setting: This qualitative study performed an exploratory content analysis of award applications submitted to the ACGME over 2 cycles in 2020 and 2021, using the constant comparative method. The research team first acknowledged their own biases related to DEI, used caution to not overinterpret the data, and performed several cross-checks during data analysis to ensure confirmability of the results. A preliminary codebook was developed and used during regular adjudication sessions. Disagreements were discussed until agreements were reached., Main Outcomes and Measures: Foundational (ie, commonly cited, high-impact, and small-effort strategies considered achievable by all programs) and aspirational (ie, potential for high impact but requiring greater effort and investment) DEI strategies used by exemplary GME programs., Results: This qualitative study included 29 award applications submitted between August 17, 2020, and January 11, 2022. Strategies spanned the education continuum from premedical students through faculty. Foundational strategies included working with schools, community colleges, and 4-year college campuses; providing structured support for visiting students; mission-driven holistic review for admissions and selection; interviewer trainings on implicit bias mitigation and on how racism and discrimination impact admission processes and advancement; interview-day DEI strategies; inclusive selection and DEI committees; mission statements that include DEI; and retention efforts to improve faculty diversity. Aspirational strategies included development of longitudinal bidirectional collaborations (eg, articulation agreements, annual workshops, funded rotations and/or research) with organizations working with applicants who were historically excluded and underrepresented in medicine, blinding metrics in residency applications, longitudinal curricula on DEI and health equity, and faculty mentoring such as affinity groups, mentored research, and joint academic-community recruitments. Findings provide residency program leadership with a menu of options at various inflection points to foster DEI within their programs., Conclusions and Relevance: The findings of this qualitative study suggest that GME programs might adopt strategies of exemplary programs to improve DEI in residency, ensure compliance with accreditation standards, and improve health outcomes for all.

Purpose: Bullying is defined as offenders abusing positions of authority and intentionally targeting individuals through persistent negative behaviors to impede education or career growth. This study sought to estimate the prevalence and nature of bullying experienced by women physician leaders in academic medicine., Method: In this survey-based study, 547 physician graduates of an executive women's leadership training program were invited to complete a survey that measured workplace bullying in 2021. Participants were asked whether and when they had been bullied, how it impacted their careers, and remedies for bullying. Descriptive statistics were used to profile mistreatment and bullying experienced by the respondents during their professional careers and the nature of bullying. Content analysis of open-ended comments was used to describe how bullying impacted women physicians and outline recommendations for bullying prevention and mitigation., Results: The survey response rate was 64.7% (354/547). Most women (302/354 [85.3%]) had experienced mistreatment during their careers, with more than half experiencing bullying while an attending physician (198/302 [65.6%]). Many women (187/302 [61.9%]) who screened positive for mistreatment also reported that they had been bullied at work. Of these 187 respondents, 173 (92.5%) experienced bullying from men and 121 (64.7%) reporting bullying from women (effect size = 0.34, P ≤ .001), and 115 (61.5%) reported that bullies were their immediate supervisors. Qualitative findings suggested that bullying harmed individuals' career advancement, mental health, reputation, and relationships with others. Many had to change roles or leave jobs. Participants proposed that initiatives by top-level leaders, clear definitions of bullying behavior, reporting mechanisms, and upstander training for faculty and staff could mitigate bullying., Conclusions: Most women physician leaders have experienced bullying. These results highlight the need to address bullying in academic medicine so that women can reach their full career potential., (Copyright © 2022 by the Association of American Medical Colleges.)

The 2021 National Academies of Sciences, Engineering, and Medicine (NASEM) report on Implementing High-Quality Primary Care identifies 5 high-level objectives regarding payment, access, workforce development, information technology, and implementation. Nine junior primary care leaders (3 internal medicine, 3 family medicine, 3 pediatrics) invited from broad geographies, practice settings, and academic backgrounds used appreciative inquiry to identify priorities for the future of primary care. Highlighting the voices of these early career clinicians, we propose a response to the report from the perspective of early career primary care physicians. Health equity must be the foundation of the future of primary care. Because Barbara Starfield's original 4 Cs (first contact, coordination, comprehensiveness, and continuity) may not be inclusive of the needs of under-resourced communities, we promote an extension to include 5 additional Cs: convenience, cultural humility, structural competency, community engagement, and collaboration. We support the NASEM report's priorities and its focus on achieving health equity. We recommend investing in local communities and preparatory programs to stimulate diverse individuals to serve in health care. Finally, we support a blended value-based care model with risk adjustment for the social complexity of our patients.Appeared as Annals "Online First" article., (© 2022 Annals of Family Medicine, Inc.)

Background: Despite increasing representation of women in medicine, gender bias remains pervasive. The authors sought to evaluate speaker introductions by gender in the grand rounds of multiple specialties at a large academic institution to understand the cultural context of this behavior and identify predictors of formality. Materials and Methods: The authors reviewed grand rounds recordings of speakers with doctorates presenting to the departments of family medicine, general surgery, internal medicine, obstetrics and gynecology, and pediatrics at one institution from 2014 to 2019. The primary outcome was whether a speaker's professional title was used as the first form of address. The authors assessed factors correlated with professional introduction using multivariable logistic regression. Results: Speakers were introduced professionally in 346/615 recordings (56.3%). Female introducers were more likely to introduce speakers professionally (odds ratio [OR]: 2.52). A significant interaction existed between speaker gender and home institution: female speakers visiting from an external institution were less likely than male external speakers to be introduced professionally (OR: 0.49), whereas female speakers internal to the institution were more likely to be introduced professionally than male internal speakers (OR: 1.75). Use of professional titles varied by specialty and was higher than average for family medicine (83.2%), surgery (75.8%), and pediatrics (64.0%) and lower for internal medicine (37.5%) and obstetrics and gynecology (50.7%). Conclusions: These findings suggest a complex relationship between gender and formality of introduction that merits further investigation. Understanding differences in culture across specialties is important to inform efforts to promote equity.

A pessimistic strain of thought is fomenting in the health studies literature regarding the status of medicine. Ioannidis's (2005) now famous finding that "most published research findings are false" and Stegenga's (2018) book-length argument for medical nihilism are examples of this. In this paper, we argue that these positions are incorrect insofar as they rest on an untenable account of the nature of facts. Proper attention to fallibilism and the social organization of knowledge, as well as Bayesian probabilities in medical reasoning, prompt us to ask why the cynics expect the results of quantitative studies to be incontrovertibly true in the first place. While we agree with Ioannidis and others' identified flaws in the medical research enterprise, and encourage rectification, we conclude that medical nihilism is not the natural outcome of the current state of research., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Increased implementation of complex genetic technologies in clinical practice emphasizes the urgency of genomic literacy and proficiency for medical professionals. We evaluated our genomic education model., Methods: We assessed the 5-day, extended format program, encompassing lectures, videos, interactive tests, practice cases, and clinical exercises. Pre- and post questionnaires assessed knowledge change, using t-tests to compare groups. Satisfaction on program completion and after 3 years were evaluated. Implementation in other centers determined acceptability., Results: During 2012-2018, 774 clinicians from multiple disciplines and career stages attended 35 programs; 334 (43%) attended the 5-day extended format. Evaluations showed significant improvement of genomic literacy (mean 15.05/100 points, p < 0.001). Residents initially had higher scores than specialists (pre: 66.3 ± 17.3 vs. 58.7 ± 16.6, respectively, p = 0.002); both significantly improved, with specialists "catching up" (post: 79.1 ± 17.2 vs. 75.7 ± 15.9, nonsignificant (NS)); there was a similar trend between fellows and subspecialists (pre: 70 ± 18 vs. 59.4 ± 16.4, respectively, p = 0.007; post: 78.6 ± 16.4 vs. 73.2 ± 17.7, respectively, NS). Younger specialists (≤10 years residency) had significantly higher pre- and post scores. Absolute improvement in scores did not depend on medical specialties., Conclusion: Our program is effective in improving genomics literacy for clinicians, irrespective of career length or expertise, and could be a model for improving skills in practical genomics for all medical professionals.

Purpose: To present an overview of the status of Medical Physics practice in Mexico, promote the legal recognition of Medical Physics high-end training, and provide information that will potentially improve the Mexican healthcare system., Methods: For the purpose of this research, the concept of "Medical Physics Professional/s" (MPP) is introduced to refer to any person/s executing the role of a clinical medical physicist (cMP) in whole or in part independent of academic profile, training or experience. A database of MPP in Mexico was built from official sources and personal communication with peers. Database records included the following fields: employer/s, specialty, academic profile, and annual income (when available)., Results: 133 centers in Mexico employ MPP, 49% of which are public institutions. 360 positions involving cMP roles were identified at the National Healthcare System (occupied by 283 MPP), 77% of which corresponded to radiation therapy. Public healthcare services hold 65% of the reported positions. Only 40% of MPP hold a graduate degree in Medical Physics, 46% of whom were located in the most densely populated region of Mexico. Of all MPP, 32% were women., Conclusions: This work allowed to clearly identify the current challenges of Medical Physics practice in Mexico, such as: insufficiency and uneven geographical distribution of qualified manpower, gender imparity, multishifting and wage gap. The products derived from this work could be used to guide the efforts to improve the Mexican healthcare system., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Objective: DPP-4 inhibitors (DPP-4i) have been shown to be effective for the management of inpatient diabetes. We report pooled data from 3 prospective studies using DPP-4i in general medicine and surgery patients with type 2 diabetes (T2D)., Methods: We combined data from 3 randomized studies comparing DPP-4i alone or in combination with basal insulin or a basal-bolus insulin regimen. Medicine (n = 266) and surgery (n = 319) patients admitted with a blood glucose (BG) between 140 and 400 mg/dL, treated with diet, oral agents, or low-dose insulin therapy were included. Patients received DPP-4i alone (n = 144), DPP-4i plus basal insulin (n = 158) or basal-bolus regimen (n = 283). All groups received correctional doses with rapid-acting insulin for BG >140 mg/dL. The primary endpoint was differences in mean daily BG between groups. Secondary endpoints included differences in hypoglycemia and hospital complications., Results: There were no differences in mean hospital daily BG among patients treated with DPP-4i alone (170 ± 37 mg/dL), DPP-4i plus basal (172 ± 42 mg/dL), or basalbolus (172 ± 43 mg/dL), P = .94; or in the percentage of BG readings within target of 70 to 180 mg/dL (63 ± 32%, 60 ± 31%, and 64 ± 28%, respectively; P = .42). There were no differences in length of stay or complications, but hypoglycemia was less common with DPP-4i alone (2%) compared to DPP-4i plus basal (9%) and basal-bolus (10%); P = .004., Conclusion: Treatment with DPP-4i alone or in combination with basal insulin is effective and results in a lower incidence of hypoglycemia compared to a basal-bolus insulin regimen in general medicine and surgery patients with T2D., Abbreviations: BG = blood glucose; BMI = body mass index; CI = confidence interval; DPP-4i = dipeptidyl peptidase-4 inhibitors; HbA1c = hemoglobin A1c; OR = odds ratio; T2D = type 2 diabetes., (© 2020 American Association of Clinical Endocrinologists. Published by Elsevier, Inc. All rights reserved.)

Abstract Coastal change is a complex combination of multi-scale processes (e.g., wave-driven cross-shore and longshore transport; dune, bluff, and cliff erosion; overwash; fluvial and inlet sediment supply; and sea-level-driven recession). Historical sea-level-driven coastal recession on open ocean coasts is often outpaced by wave-driven change. However, future sea-level-driven coastal recession is expected to increase significantly in tandem with accelerating rates of global sea-level rise. Few models of coastal sediment transport can resolve the multitude of coastal-change processes at a given beach, and fewer still are computationally efficient enough to achieve large-scale, long-term simulations, while accounting for historical behavior and uncertainties in future climate. Here, we show that a scalable, data-assimilated shoreline-change model can achieve realistic simulations of long-term coastal change and uncertainty across large coastal regions. As part of the modeling case study of the U.S. South Atlantic Coast (Miami, Florida to Delaware Bay) presented here, we apply historical, satellite-derived observations of shoreline position combined with daily hindcasted and projected wave and sea-level conditions to estimate long-term coastal change by 2100. We find that 63 to 94% of the shorelines on the U.S. South Atlantic Coast are projected to retreat past the present-day extent of sandy beach under 1.0 to 2.0 m of sea-level rise, respectively, without large-scale interventions.

Objetivo. Sistematizar evidências sobre o efeito de intervenções mundiais para a redução do consumo e/ou venda de bebidas alcoólicas. Método. Mapa de evidências que, a partir de buscas em nove bases bibliográficas, incluiu 182 estudos de revisões sistemáticas com ou sem metanálises, revisões de intervenções e revisões de revisões. Os estudos avaliaram o efeito de intervenções - agrupadas em conjuntos abrangentes de ações: comunicação para mudança de comportamento; ambientes promotores da saúde e mudanças dos sistemas - sobre dois desfechos de interesse: redução de consumo e redução da compra e/ou venda de álcool. Resultados. Foram registradas 207 associações entre diferentes intervenções e desfechos, com destaque para intervenções de comunicação para mudança de comportamento (81,64%) e para o desfecho de redução de consumo (98,55%). A maioria das associações apresentou efeito positivo (40,58%), inconclusivo (28,99%) ou potencialmente positivo (26,57%). Das intervenções com resultado positivo ou potencialmente positivo, destacam-se o monopólio de vendas de bebidas alcoólicas pelo governo, controle de densidade de pontos de venda, cobrança de preço mínimo por unidade, advertências sanitárias em rótulo de bebidas alcoólicas e múltiplas intervenções integradas. Conclusão. Espera-se que o presente mapa auxilie formuladores de políticas públicas e profissionais de saúde na adaptação de experiências para seus contextos de atuação, estimulando ações intersetoriais para reduzir o consumo de álcool.

Abstract In super-aged societies, dementia has become a critical issue, underscoring the urgent need for tools to assess cognitive status effectively in various sectors, including financial and business settings. Facial and speech features have been tried as cost-effective biomarkers of dementia including Alzheimer’s disease (AD). We aimed to establish an easy, automatic, and extensive screening tool for AD using a chatbot and artificial intelligence. Smile images and visual and auditory data of natural conversations with a chatbot from 99 healthy controls (HCs) and 93 individuals with AD or mild cognitive impairment due to AD (PwA) were analyzed using machine learning. A subset of 8 facial and 21 sound features successfully distinguished PwA from HCs, with a high area under the receiver operating characteristic curve of 0.94 ± 0.05. Another subset of 8 facial and 20 sound features predicted the cognitive test scores, with a mean absolute error as low as 5.78 ± 0.08. These results were superior to those obtained from face or auditory data alone or from conventional image depiction tasks. Thus, by combining spontaneous sound and facial data obtained through conversations with a chatbot, the proposed model can be put to practical use in real-life scenarios.

Aim: In this study, the best corrected visual acuity (BCVA) and refraction in preterm-born infants in South-Eastern Bulgaria after 12 years of treatment for type 1 prethreshold retinopathy of prematurity were presented, and the outcomes of laser treatment and cryotherapy were compared. Materials and methods: Since 2010, we have treated 319 eyes of 164 prematurely born children for type 1 prethreshold retinopathy of prematurity and were prospectively followed up. The mean (range) gestational age was 28.6 weeks of gestation (23–33) and the mean (range) birth weight was 1143 g (570–1990). Cryotherapy was applied on 76 eyes (23.2%), laser was used in 215 eyes (65.5%), anti-VEGF – in 10 eyes (3%) and surgery – in 18 eyes (5.5%). Twelve children (24 eyes, 7.3%) were lost to the follow-up. BCVA was tested in 114 eyes and refraction in 190 eyes. Because of the small number of eyes treated surgically or with anti-VEGF (18 and 10, respectively), these children’s eyes were excluded from the statistical analysis. Results: Fifty eyes showed BCVA between 0.6 and 1.0; 25 eyes – between 0.2 and 0.5; 5 eyes – between 0.04 and 0.1; 5 eyes between light perception –0.03 and 4 eyes were totally blind. Laser-treated eyes showed statistically significantly higher BCVA compared to the cryotherapy treated eyes (Fisher’s exact test, p=0.012). Myopia (any myopic refraction) was found in 50 eyes; hyperopia (>+2 D) – in 20 eyes; astigmatism (difference between the two principal meridians >0.75 D) – in 70 eyes, and emmetropia – in 30 eyes. Although in the laser-treated group more eyes showed emmetropic and hyperopic refraction compared to cryo treated group (25 eyes vs. 7 eyes – emmetropia and 15 eyes vs. 5 eyes – hyperopia, respectively), the difference did not reach statistical significance (Fisher’s exact test, p=0.106). Conclusion: Timely treatment of type 1 prethreshold retinopathy of prematurity leads to very good anatomical and functional results. Laser treatment leads to significantly higher BCVA, compared to cryotherapy. Emmetropia and hyperopia are more commonly seen in laser-treated eyes.

Abstract Background Empathy declines during medical training, despite its importance. Methodology In this randomized controlled trial, we assessed the impact of Zoom improv on medical student empathy using a concurrent mixed-methods approach. Quantitative assessment with three survey tools and qualitative assessment by content analysis of Zoom session field notes were conducted. Results Zoom improv participants had higher empathy scores in perspective-taking and fantasy and lower scores in personal distress compared with the control group. Medical students who participated in Zoom improv exercised emotional expression, active listening, and giving “gifts,” which apply to healthcare settings in which affirming team members with empathic concern can advance communication, patient rapport, and teamwork. Discussion This pilot study highlights promising findings for the incorporation of Zoom improv in medical education, including enhanced empathy, self-reflection, and understanding how these skills impact work in healthcare. Future studies may expand on the optimal timing to teach improv. Future studies conducted on virtual platforms may also further investigate our finding that the fantasy domain of empathy increases after Zoom improv sessions, whereas this increase in fantasy was absent from previous in-person studies. Given the increase in telehealth and virtual medical visits, exercising empathy skills through a screen during training may be an important addition to medical curricula.

Abstract Biofilm formation and toxin production are some of the virulence factors of Clostridioides difficile (C. difficile), which causes hospital-acquired C. difficile infection (HA-CDI). This work investigated the prevalence and distribution of different strains recovered from HA-CDI patients hospitalized in 4 medical centres across Israel, and characterized strains' virulence factors and antibiotic susceptibility. One-hundred and eighty-eight faecal samples were collected. C. difficile 's toxins were detected by the CerTest Clostridium difficile GDH + Toxin A + B combo card test kit. Toxin loci PaLoc and PaCdt were detected by whole-genome sequencing (WGS). Multi-locus sequence typing (MLST) was performed to classify strains. Biofilm production was assessed by crystal violet. Antibiotic susceptibility was determined using Etest. Fidaxomicin susceptibility was tested via agar dilution. Sequence type (ST) 42 was the most (13.8%) common strain. All strains harboured the 2 toxins genes; 6.9% had the binary toxin. Most isolates were susceptible to metronidazole (98.9%) and vancomycin (99.5%). Eleven (5.85%) isolates were fidaxomicin-resistant. Biofilm production capacity was associated with ST (p

Brown tumors are rare skeletal manifestations of hyperparathyroidism. It is a form of osteitis fibrosa cystica caused by hyperparathyroidism due to excessive secretion of parathyroid hormone. Then, hypercalcemia results in excessive osteoclastic activity in the bones. Brown tumors are considered a rare complication of hyperparathyroidism, as their reported existence is only about 1.5-4.5%. Herein, we report a rare case of brown tumor arising from the left maxilla due to primary hyperparathyroidism, its challenge in diagnosis with giant cell tumor, and its literature review.

Background Studies on the clinical characteristics of retinoblastoma in Indonesia have been limited, even though retinoblastoma is the most common pediatric ocular malignancy worldwide and the second-most common pediatric malignancy in Indonesia. The estimated patient survival rate in lower-middle-income countries is 77%, and survival is highly dependent on early diagnosis and therapy. Objective To identify the clinical characteristics of retinoblastoma in patients at the Cicendo National Eye Hospital, as an Indonesian tertiary eye hospital. Methods This retrospective, observational study included pediatric patients

Abstract Tongue brushing improves respiratory function in older adults. Considering connection between the respiratory-related and suprahyoid muscles, this study aimed to investigate whether tongue-brushing interventions can improve myoelectric activity during respiration. A six-week randomized controlled trial was conducted in Kitakyushu, Japan, with 50 participants aged ≥ 65 years. The participants were allocated to the intervention (tongue brushing with routine oral hygiene) or control (routine oral hygiene alone) groups. Surface electromyography (sEMG) was used to assess the myoelectric activity of the suprahyoid muscles during inhalation, exhalation, and forced vital capacity (FVC). A survey was conducted at baseline and the end of the follow-up period. Thirty-six participants were recruited for the analysis. The root mean squares (RMS) of sEMG during exhalation increased significantly at the end of the follow-up period compared with that at baseline in the intervention group [48.7 (18.0–177.5) vs. 64.9 (21.6–163.0), p = 0.001], but not in the control group. The generalized linear model revealed that the ratio of change in FVC was correlated with the change in the RMS of sEMG of the suprahyoid muscles during exhalation after adjusting for potential confounders. Tongue brushing enhances the myoelectric activity of the suprahyoid muscle.

Aim: The PREDICT tool is used to estimate survival in breast cancer patients according to the types of treatment given. This study aimed to assess the accuracy of the PREDICT tool and identify the prognostic factors for survival in patients with breast cancer.Material and Methods: A retrospective study was performed based on data collected from the Hospital Sultanah Nur Zahirah, Terengganu, Malaysia. All female patients diagnosed with stage I to IV breast cancer were identified from the year 2011 to 2017.Results: Based on data from 355 eligible patients, the predicted and observed 5-year overall survival rates were 75.8% and 75.2%, respectively. The model performed fairly well, with the area under the curve (AUC) of 0.747 (95% confidence interval (CI): 0.69-0.81) in the predicted 5-year overall survival. Among the 585 patients diagnosed with stage I to IV breast cancer, stage at the presentation (stage III hazard ratio (HR): 5.80, 95% CI: 1.69-19.94, p=0.005, stage IV HR: 10.61, 95% CI: 3.09-36.49, p

Abstract The study was formulated to identify the effect of Mangifera indica leaf extract in inhibiting the growth and metamorphosis of Culex quinquefasciatus larva. Bioassay-guided extraction identified the bioactive fraction, after which GC-MS characterized it. The larvicidal activity was analyzed by administrating extract in various concentrations and then subjecting the mortality rate for probit analysis. The morphological and physiological impact upon larvae was understood by histological analysis and acetylcholinesterase activity assay. The results suggested that the extract possessed a high degree of larvicidal activity, whereas the Dose50 was 225.158 ± 15.168 with a Total Chi-Square of 13.09 and p-value of 0.11. The histological studies revealed notable aberrations among the study subjects compared to the control group due to diminished abdominal tissue integrity. It was also observed that the extract could inhibit the acetylcholinesterase activity, with an LD 50 of 0.9512 µg/ml. The observations made in these studies may be utilized to develop a potential larvicidal agent that could act upon multiple targets.

Abstract Rifaximin is FDA-approved for treatment of irritable bowel syndrome with diarrhea (IBS-D), but poor solubility may limit its efficacy against microbes in the mucus layer, e.g. Escherichia coli. Here we evaluate adding the mucolytic N-acetylcysteine (NAC) to improve rifaximin efficacy. In a resazurin checkerboard assay, combining rifaximin with NAC had significant synergistic effects in reducing E. coli levels. The optimal rifaximin + NAC combination was then tested in a validated rat model of IBS-D (induced by cytolethal distending toxin [CdtB] inoculation). Rats were inoculated with vehicle and treated with placebo (Control-PBS) or rifaximin + NAC (Control-Rif + NAC, safety), or inoculated with CdtB and treated with placebo (CdtB-PBS), rifaximin (CdtB-Rifaximin), or rifaximin + NAC (CdtB-Rif + NAC) for 10 days. CdtB-inoculated rats (CdtB-PBS) developed wide variability in stool consistency (P = 0.0014) vs. controls (Control-PBS). Stool variability normalized in rats treated with rifaximin + NAC (CdtB-Rif + NAC) but not rifaximin alone (CdtB-Rifaximin). Small bowel bacterial levels were elevated in CdtB-PBS rats but normalized in CdtB-Rif + NAC but not CdtB-Rifaximin rats. E. coli and Desulfovibrio spp levels (each associated with different IBS-D microtypes) were also elevated in CdtB-inoculated (CdtB-PBS) but normalized in CdtB-Rif + NAC rats. Cytokine levels normalized only in CdtB-Rif + NAC rats, in a manner predicted to be associated with reduced diarrhea driven by reduced E. coli. These findings suggest that combining rifaximin with NAC may improve the percentage of IBS-D patients responding to treatment.

Abstract Tracking trajectories of body size in children provides insight into chronic disease risk. One measure of pediatric body size is body mass index (BMI), a function of height and weight. Errors in measuring height or weight may lead to incorrect assessment of BMI. Yet childhood measures of height and weight extracted from electronic medical records often include values which seem biologically implausible in the context of a growth trajectory. Removing biologically implausible values reduces noise in the data, and thus increases the ease of modeling associations between exposures and childhood BMI trajectories, or between childhood BMI trajectories and subsequent health conditions. We developed open-source algorithms (available on github) for detecting and removing biologically implausible values in pediatric trajectories of height and weight. A Monte Carlo simulation experiment compared the sensitivity, specificity and speed of our algorithms to three published algorithms. The comparator algorithms were selected because they used trajectory information, had open-source code, and had published verification studies. Simulation inputs were derived from longitudinal epidemiological cohorts. Our algorithms had higher specificity, with similar sensitivity and speed, when compared to the three published algorithms. The results suggest that our algorithms should be adopted for cleaning longitudinal pediatric growth data.

In Israel, prevalence of sequence type 913, staphylococcal cassette chromosome mecIVa, spa type t991 methicillin-resistant Staphylococcus aureus lineage has surged among pediatric populations, predominantly in Arab and Orthodox Jewish communities. Antimicrobial resistance patterns vary by demographics. This lineage's spread and microevolution in the Middle East underscore the need for ongoing surveillance.

Background: Family medicine (FM) is a medical specialty that provides continuing, comprehensive health care for the individual and the family. This study aimed to describe Lebanese citizens’ knowledge, attitudes, and practices toward FM as a specialty. Methods: This is a national cross-sectional phone-based survey targeting the knowledge of the public about FM and its scope of practice. Questions were asked whether participants had primary health care doctors and their specialties Results: A total of 373 participants were included, with a response rate of 85.2%. Two-thirds were aware of the specialty of FM, while only 16.6% of the participants had previously visited a family physician. Most participants (69.7%) had a doctor they regularly consulted. One-third of participants had a general practitioner as their regular doctor. More than 80% of the participants agreed that FM physicians treat all family members with common and chronic diseases. Around 60% to 75% of participants knew that family physicians provide medical care to children, treat patients with psychiatric impairments, and perform minor surgeries. There was a significant gap in the participants’ knowledge of FM physicians’ role in managing obstetric or gynecologic patients. Conclusion: Despite public awareness of FM, limited understanding and system challenges hinder its utilization in Lebanon. Educational campaigns, government-supported FM practices, and collaborations with public health initiatives are crucial to bridging the knowledge gap and establishing FM as the cornerstone of primary care. This knowledge gap challenges the specialty’s identity and necessitates promoting FM as the cornerstone of primary care, potentially requiring a system-wide endorsement.

Abstract In the face of global adversities such as pandemics, military conflicts, and socio-political unrest, the resilience and well-being of populations can be severely tested. This study examines the fluctuating levels of distress within the Israeli population over a period of 2.5 years, encompassing events like the COVID-19 pandemic and various socio-political and security crises. Utilizing a quasi-longitudinal design, data were collected at thirteen time-points, mirroring the demographic makeup of the Israeli Jewish adult population. Measures of psychological distress, societal and individual resilience, hope, morale, and perceived danger were assessed, alongside demographic variables. Statistical analyses included ANOVA and stepwise regression models. Distress levels displayed significant oscillations in response to adverse events. High distress was noted during the latter stages of the study, particularly following a major security incident on October 7, 2023. The regression analyses identified morale and perceived danger as consistent important associations with distress, with individual resilience also inversely related across all time points. The study reveals the dynamic nature of psychological distress in relation to a range of adversities. Morale emerged as a key buffer against distress, whereas perceived danger was a significant stressor, especially during acute- existential threats. These findings have important implications for mental health interventions and policy-making aimed at fostering resilience and mitigating distress in crisis conditions.

Abstract Background 7 T cardiac magnetic resonance imaging (MRI) studies may enable higher precision in clinical metrics like cardiac function, ventricular mass, and more. Higher precision may allow early detection of functional impairment and early evaluation of treatment responses in clinical practice and pre-clinical studies. Methods: Seven female German Landrace pigs were scanned prior to and at three time points (3–4 days, 7–10 days, and ~60 days) post myocardial infarction using a whole body 7 T system and three radiofrequency (RF) coils developed and built in-house to accompany animal growth. Results: The combination of dedicated RF hardware and 7 T MRI enables a longitudinal study in a pig model of acute and chronic infarction, providing consistent blood tissue contrast and high signal-to-noise ratio (SNR) in measurements of cardiac function, as well as low coefficients of variation (CoV) for ejection fraction (CoVintra-observer: 2%, CoVinter-observer: 3.8%) and infarct size (CoVintra-observer: 8.4%, CoVinter-observer: 3.8%), despite drastic animal growth. Conclusions: Best results are achieved via manual segmentation. We define state-of-the-art procedures for large animal studies at 7 T.

ABSTRACT The off‐label use of dupilumab has proven to be an effective treatment option for severe chronic actinic dermatitis (CAD). We present the first case of CAD presenting with dupilumab‐induced erythrodermic psoriasiform dermatitis. A modified, spaced dupilumab dosing regimen, combined with cyclosporine, successfully managed both conditions, offering a promising strategy for managing dupilumab adverse effects while maintaining control over chronic actinic dermatitis.

BackgroundTo reduce leprosy risk in contacts of patients with leprosy by around 50%, the World Health Organization (WHO) recommends leprosy post-exposure prophylaxis (PEP) using single-dose rifampicin (SDR). Results from a cluster randomized trial in the Comoros and Madagascar suggest that PEP with a double dose of rifampicin led to a similar reduction in incident leprosy, prompting the need for stronger PEP. The objective of this Phase 2 trial was to assess safety of a bedaquiline-enhanced PEP regimen (intervention arm, bedaquiline 800 mg with rifampicin 600 mg, BE-PEP), relative to the WHO recommended PEP with rifampicin 600 mg alone (control arm, SDR-PEP).Methods and findingsFrom July 2022 to January 2023, consenting participants were screened for eligibility, including a heart rate-corrected QT interval (QTc) 50 ms or exceeded 450 ms after PEP administration. Per protocol, all children were analyzed together, with no significant difference in mean QTc increase for BE-PEP compared to SDR-PEP, although non-inferiority of BE-PEP in children was not demonstrated in unadjusted analysis, as the upper limit of the 95% CI of 10.4 ms exceeded the predefined margin of 10 ms. Adjusting for baseline QTc, the regression coefficient and 95% CI (3.3; -1.4, 8.0) met the 10 ms non-inferiority margin. No significant differences in ALT or AST levels were noted between the intervention and control arms, although a limitation of the study was false elevation of ALT/AST during adult recruitment due to a technical error. In both study arms, one serious adverse event was reported, both considered unlikely related to the study drugs. Dizziness, nausea, headache, and diarrhea among adults, and headaches in children, were nonsignificantly more frequently observed in the BE-PEP group.ConclusionsIn this study, we observed that safety of single-dose bedaquiline 800 mg in combination with rifampicin is comparable to rifampicin alone, although non-inferiority of QTc changes was demonstrated in children only after adjusting for the baseline QTc measurements. A Phase 3 cluster randomized efficacy trial is currently ongoing in the Comoros.Trial registrationClinicalTrials.gov NCT05406479.

BackgroundPostpartum depression (PPD) is associated with significant health consequences for the parent and child. Current recommendations for PPD prevention require intense health care system resources. Evidence-based interventions for PPD prevention that do not further burden the health care system are needed. Evidence suggests that physical activity (PA) can generally reduce depressive symptoms. Technology-based interventions may help decrease common barriers to PA. ObjectiveThis study aims to report the protocol and provide a data overview of the POstpartum Wellness study (POW)—an effectiveness trial evaluating whether an eHealth PA intervention tailored for postpartum individuals increased PA and decreased depressive symptoms among individuals at high PPD risk. MethodsThis remote parallel-group randomized controlled trial included postpartum individuals with a history of depression or at least moderate current depressive symptoms not meeting the PPD diagnostic threshold and with low PA levels from an integrated health care delivery system. Participants were randomized to an eHealth PA intervention or usual care. The intervention group received access to a library of web-based workout videos designed for postpartum individuals, which included interaction with their infants. At baseline and follow-up (3 and 6 months), PA was measured using questionnaires and a wrist-worn accelerometer. Depressive symptoms were measured using the Patient Health Questionnaire-8 (PHQ-8). Data were collected to assess exploratory outcomes of sleep, perceived stress, anxiety, parent-infant bonding, and infant development. ResultsThe study was funded in January 2020. Participants were enrolled via REDCap (Research Electronic Data Capture) or telephonically between November 2020 and September 2022; data collection ended in April 2023. Randomized participants (N=99) were 4 months post partum at baseline with moderately severe depressive symptoms (mean PHQ-8 score 12.6, SD 2.2). Intervention (n=50) and usual care (n=49) groups had similar sociodemographic characteristics, months post partum, baseline depressive symptoms, number of children at home, and prepregnancy PA levels. Retention in assessments was ≥66% for questionnaires and ≥48% for accelerometry, with modest differences by group. At 3-month follow-up, 73 of 99 (74%) participants (intervention: 35/50, 70%; usual care: 38/49, 78%) completed questionnaires; 53 of 99 (54%) wore the accelerometer for 7 days (27 of 50 (54%) intervention, 26 of 49 (53%) usual care). At 6-month follow-up, 66 of 99 (67%) participants (30 of 50 (60%) intervention, 36 of 49 (73%) usual care) completed questionnaires and 43 of 99 (43%) wore the accelerometer for 7 days (21 of 50 (42%) intervention, 22 of 49 (45%) usual care). Data analysis is completed, and a manuscript with these findings is currently under review for publication. ConclusionsThe POW trial evaluates the effectiveness of an eHealth PA intervention for improving depressive symptoms and increasing PA among postpartum individuals at high PPD risk. Results have implications for the design and delivery of behavioral interventions among vulnerable patients. Trial RegistrationClinicalTrials.gov NCT04414696; https://clinicaltrials.gov/ct2/show/NCT04414696 International Registered Report Identifier (IRRID)DERR1-10.2196/56882

Background Janus kinase inhibitors are an effective option for achieving sustained remission or low disease activity in patients with rheumatoid arthritis (RA) following inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs. Filgotinib is a Janus kinase 1–preferential inhibitor available in two doses for moderate-to-severe RA. We report the long-term efficacy and safety of filgotinib.Methods In the ongoing long-term extension study FINCH 4 (NCT03025308), patients continue filgotinib 200 mg or 100 mg from FINCH 1, 2 or 3 or receive filgotinib 200 mg or 100 mg de novo. Efficacy assessments up to week 156 include American College of Rheumatology 20% response (ACR20), Disease Activity Score 28 using C-reactive protein of

BackgroundLosing a loved one, through death or separation, counts among the most stressful life events and is detrimental to health and well-being. About 15% of people show clinically significant difficulties coping with such an event. Web-based interventions (WBIs) are effective for a variety of mental health disorders, including prolonged grief. However, no validated WBI is available in French for treating prolonged grief symptoms. ObjectiveThis study aimed to compare the efficacy and adherence rates of 2 WBIs for prolonged grief symptoms following the loss of a loved one through death or romantic separation. MethodsLIVIA 2.0 was developed relying on theoretical and empirical findings on bereavement processes and WBIs, and is compared with LIVIA 1, which has already demonstrated its efficacy. We conducted a randomized controlled trial and provided on-demand guidance to participants. Outcomes were assessed through web-based questionnaires before the intervention, after the intervention (12 weeks later), and at follow-up (24 weeks later). Primary outcomes were grief symptoms, depressive symptoms, and well-being. Secondary outcomes were anxiety symptoms, grief coping strategies, aspects related to self-identity, and program satisfaction. ResultsIn total, 62 participants were randomized (intent-to-treat [ITT] sample), 29 (47%) in LIVIA 2.0 (active arm) and 33 (53%) in LIVIA 1 (control arm). The dropout rate was 40% (37/62), and 10 participants were removed due to exclusion criteria, leading to a final per-protocol sample of 27 (44%) completers who differed from noncompleters only based on reporting fewer anxiety symptoms (t60=3.03; P=.004). Participants who are separated reported more grief symptoms (t60=2.22; P=.03) and attachment anxiety (t60=2.26; P=.03), compared to participants who are bereaved. There were pre-post within-group differences for both programs in the ITT sample, with significant reductions in grief (Cohen d=−0.90), depressive symptoms (Cohen d=−0.31), and centrality of the loss (Cohen d=−0.45). The same pattern was observed in the per-protocol sample, with the exception that anxiety symptoms also significantly diminished (Cohen d=−0.45). No difference was found in efficacy between the 2 programs (all P>.33). Participants (ITT sample) reported overall high levels of program satisfaction (mean 3.18, SD 0.54; over a maximum of 4). Effect stability was confirmed at the 6-month follow-up for all outcomes, with an improvement in self-concept clarity. ConclusionsThe 2 grief-related WBIs were effective in reducing grief, depressive and anxiety symptoms for participants who are bereaved or separated. The analyses did not reveal any pre-post between-group differences, suggesting that the innovations brought to LIVIA 2.0 did not significantly affect the outcome. However, caution is warranted with the interpretation of the results given the limited power of the sample, which only allows the detection of medium effect sizes. Trial RegistrationClinicalTrials.gov NCT05219760; https://clinicaltrials.gov/study/NCT05219760 International Registered Report Identifier (IRRID)RR2-10.2196/39026

Key Clinical Message Acute digital ischemia is a rare manifestation of anti‐synthetase syndrome in the absence of Raynaud's phenomenon. A high index of suspicion may result in early diagnosis and better clinical outcomes. Abstract A 61‐year‐old male patient was admitted to the hospital for worsening arthralgias with morning stiffness lasting hours, as well as left sided headaches, and jaw pain while eating. He had significant weight loss and subjective fever at home. Multiple fingers and toes were noted to be ischemic. His laboratory workup was pertinent for significantly elevated inflammatory markers, and mild Creatinine kinase elevation. Chest imaging and later lung biopsy were notable for organizing pneumonia. Conventional angiogram showed evidence of significant digital disease without collaterals. Subsequent autoimmune screening tests with extended myositis‐specific and myositis‐associated panels revealed a strongly positive anti‐PL‐12 antibody and moderately positive anti‐ SSA‐52KD IgG ab. After ruling out infectious etiologies and malignancy, anti‐synthetase syndrome (ASyS) diagnosis was considered in the presence of ischemic digits, organizing pneumonia, polyarthralgia, constitutional symptoms, increased inflammatory markers and positive antibodies. The patient was treated with high dose prednisone and mycophenolate mofetil along with amlodipine and sildenafil for digital vasodilation. Acute digital ischemia may be the first manifestation of ASyS with ILD. A high index of suspicion is warranted for early diagnosis and better outcomes.

Introduction Breastfeeding is crucial in infant nutrition and bonding, recommended for at least 6 months and up to 2 years postpartum, providing health benefits for both infants and mothers. However, nipple trauma is common among lactating mothers. Moisturising therapies, such as hydrogel application, aim to promote the healing of nipple wounds. Despite various interventions proposed, comprehensive reviews evaluating the efficacy of moisturising therapies for nipple trauma are lacking. This review aims to appraise the effectiveness of moisturising therapy, particularly tailored for nipple trauma in lactating women.Methods and analysis This systematic review protocol adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines and is registered in the International Prospective Register of Systematic Reviews. The focus will be on both randomised and non-randomised controlled trials addressing the treatment of nipple trauma in lactating women. In this context, ‘moisturising therapy’ is categorised as a non-pharmacological intervention applied directly to the nipple, excluding treatments for bacterial or fungal infections. The primary outcomes will include measures of the healing efficiency of nipple trauma and reduction in nipple pain. Searches will be conducted without date restrictions across multiple databases, including PubMed, CINAHL, the Cochrane Library, Web of Science, CiNii Research and Ichushi-Web, in addition to exploration of grey literature. Two independent reviewers will manage all stages of the review process, under the supervision of a third reviewer. Data extraction will encompass participant demographics, study methodologies, sample specifics and measured outcomes. Quality assessment will be conducted using the Joanna Briggs Institute Appraisal Checklist Tools.Ethics and dissemination Ethics approval is not required for this study. The findings of this review will be disseminated through academic publications, detailed reports and presentations at relevant conferences.PROSPERO registration number CRD42023481761.

Abstract Nowadays, scientists are currently attempting to lessen the harmful effects of chemicals on the environment. Stability testing identifies how a drug’s quality changes over time. The current work suggests a first and sustainable differential pulse voltammetry technique for quantifying difluprednate (DIF) as an anti-inflammatory agent in the presence of its alkaline degradation product (DEG). The optimum conditions for the developed method were investigated with a glassy carbon electrode and a scan rate of 100 mV s−1. The linearity range was 2.0 × 10−7–1.0 × 10−6 M for DIF. DIF was found to undergo alkaline degradation, when refluxed for 8 h using 2.0 M NaOH, and DEG was successfully characterized utilizing IR and MS/MS. The intended approach demonstrated the selectivity for DIF identification in pure, pharmaceutical, and degradation forms. The student’s t-test and F value were used to compare the suggested and reported approaches statistically. The results were validated according to ICH requirements. The greenness of the studied approach was evaluated using the Green Analytical Procedure Index and the Analytical Greenness metric. Additionally, the whiteness features of the proposed approach were examined with the recently released red, green, and blue 12 model, and the recommended strategy performed better than the reported approaches in greenness and whiteness.

Abstract COVID-19 vaccines have been effective in preventing severe illness, hospitalization and death, however, the effectiveness diminishes with time. Here, we evaluated the longevity of antibodies generated by COIVD-19 vaccines and the risk of (re)infection in Bangladeshi population. Adults receiving two doses of AstraZeneca, Pfizer, Moderna or Sinopharm vaccines were enrolled at 2–4 weeks after second dosing and followed-up at 4-monthly interval for 1 year. Data on COVID-like symptoms, confirmed COVID-19 infection, co-morbidities, and receipt of booster dose were collected; blood was collected for measuring spike (S)- and nucleocapsid (N)-specific antibodies. S-specific antibody titers reduced by ~ 50% at 1st follow-up visit and continued to decline unless re-stimulated by booster vaccine dose or (re)infection. Individuals infected between follow-up visits showed significantly lower S-antibody titers at preceding visits compared to the uninfected individuals. Pre-enrolment infection between primary vaccination dosing exhibited 60% and 50% protection against reinfection at 5 and 9 months, respectively. mRNA vaccines provided highest odds of protection from (re)infection up to 5 months (Odds Ratio (OR) = 0.08), however, protection persisted for 9 months in AstraZeneca vaccine recipients (OR = 0.06). In conclusion, vaccine-mediated protection from (re)infection is partially linked to elevated levels of S-specific antibodies. AstraZeneca vaccine provided the longest protection.

Abstract Cardiac magnetic resonance (CMR) imaging allows precise non-invasive quantification of cardiac function. It requires reliable image segmentation for myocardial tissue. Clinically used software usually offers automatic approaches for this step. These are, however, designed for segmentation of human images obtained at clinical field strengths. They reach their limits when applied to preclinical data and ultrahigh field strength (such as CMR of pigs at 7 T). In our study, eleven animals (seven with myocardial infarction) underwent four CMR scans each. Short-axis cine stacks were acquired and used for functional cardiac analysis. End-systolic and end-diastolic images were labelled manually by two observers and inter- and intra-observer variability were assessed. Aiming to make the functional analysis faster and more reproducible, an established deep learning (DL) model for myocardial segmentation in humans was re-trained using our preclinical 7 T data (n = 772 images and labels). We then tested the model on n = 288 images. Excellent agreement in parameters of cardiac function was found between manual and DL segmentation: For ejection fraction (EF) we achieved a Pearson’s r of 0.95, an Intraclass correlation coefficient (ICC) of 0.97, and a Coefficient of variability (CoV) of 6.6%. Dice scores were 0.88 for the left ventricle and 0.84 for the myocardium.

Abstract Background Trigonocephaly occurs due to the premature fusion of the metopic suture, leading to a triangular forehead and hypotelorism. This condition often requires surgical correction for morphological and functional indications. Metopic ridges also originate from premature metopic closure but are only associated with mid-frontal bulging; their surgical correction is rarely required. Differential diagnosis between these two conditions can be challenging, especially in minor trigonocephaly. Methods Two hundred seven scans of patients with trigonocephaly (90), metopic rigdes (27), and controls (90) were collected. Geometric morphometrics were used to quantify skull and orbital morphology as well as the interfrontal angle and the cephalic index. An innovative method was developed to automatically compute the frontal curvature along the metopic suture. Different machine-learning algorithms were tested to assess the predictive power of morphological data in terms of classification. Results We showed that control patients, trigonocephaly and metopic rigdes have distinctive skull and orbital shapes. The 3D frontal curvature enabled a clear discrimination between groups (sensitivity and specificity > 92%). Furthermore, we reached an accuracy of 100% in group discrimination when combining 6 univariate measures. Conclusion Two diagnostic tools were proposed and demonstrated to be successful in assisting differential diagnosis for patients with trigonocephaly or metopic ridges. Further clinical assessments are required to validate the practical clinical relevance of these tools.

Abstract Background Reducing overweight and obesity has been a longstanding focus of public health messaging and physician–patient interactions. Clinical guidelines by major public health organizations describe both overweight and obesity as risk factors for mortality and other health conditions. Accordingly, a majority of primary care physicians believe that overweight BMI (even without obesity) strongly increases mortality risk. Main points The current evidence base suggests that although both obese BMI and underweight BMI are consistently associated with increased all-cause mortality, overweight BMI (without obesity) is not meaningfully associated with increased mortality. In fact, a number of studies suggest modest protective, rather than detrimental, associations of overweight BMI with all-cause mortality. Given this current evidence base, clinical guidelines and physician perceptions substantially overstate all-cause mortality risks associated with the range of BMIs classified as “overweight” but not “obese.” Discrepancies between evidence and communication regarding mortality raise the question of whether similar discrepancies exist for other health outcomes. Conclusions Health communication that inaccurately conveys current evidence may do more harm than good; this applies to communication from health authorities to health practitioners as well as to communication from health practitioners to individual patients. We give three recommendations to better align health communication with the current evidence. First, recommendations to the public and health practitioners should distinguish overweight from obese BMI and at this time should not describe overweight BMI as a risk factor for all-cause mortality. Second, primary care physicians’ widespread misconceptions about overweight BMI should be rectified. Third, the evidence basis for other potential risks or benefits of overweight BMI should be rigorously examined and incorporated appropriately into health communication.

Aim: Diverticular disease is one of the most common gastrointestinal disorders to date, with a notable rising trend in developing countries. However, the proportion of colonic diverticulosis and its associated factors among patients who have undergone colonoscopy remains controversial. This study aimed to determine the local data on the proportion of diverticular disease in the community, its complications, the association of diverticulosis with diabetes mellitus and hypertension, as well as demographic characteristics. Material and Methods: A retrospective review of medical records was performed among patients who had undergone colonoscopy between January and December 2019. Demographic and clinical characteristics, the presence of diabetes mellitus, hypertension, and diverticular disease and its complications were examined, and the association of diverticular disease and its complications with demographic and clinical characteristics were analyzed. Results: Out of 221 patients, 12.7% (n=28) of them had diverticular diseases with a slightly predominant right-sided occurrence (42.9%, n=12). There were significant associations with age (p=0.002), ethnicity (p=0.011), and hypertension (p=0.036), but not with gender and diabetes mellitus (p=0.261, and p=0.334, respectively). There was no significant association between hypertension and recurrence of complicated diverticulitis (p=0.741), septic complications (p=0.678), and diverticular bleeding (p=0.243). Diabetes mellitus was significantly associated with diverticular bleeding complications (p=0.001) but not with septic complications (p=0.418) and recurrence of complicated diverticulitis (p=0.629). Conclusion: This study showed almost a similar percentage of diverticulosis compared to previous local studies. Age, ethnicity, and hypertension were associated with the presence of diverticulosis, and diabetes mellitus was associated with diverticular bleeding.

Abstract Plasma metabolomics holds potential for precision medicine, but limited information is available to compare the performance of such methods across multiple cohorts. We compared plasma metabolite profiles after an overnight fast in 11,309 participants of five population-based Swedish cohorts (50–80 years, 52% women). Metabolite profiles were uniformly generated at a core laboratory (Metabolon Inc.) with untargeted liquid chromatography mass spectrometry and a comprehensive reference library. Analysis of a second sample obtained one year later was conducted in a subset. Of 1629 detected metabolites, 1074 (66%) were detected in all cohorts while only 10% were unique to one cohort, most of which were xenobiotics or uncharacterized. The major classes were lipids (28%), xenobiotics (22%), amino acids (14%), and uncharacterized (19%). The most abundant plasma metabolome components were the major dietary fatty acids and amino acids, glucose, lactate and creatinine. Most metabolites displayed a log-normal distribution. Temporal variability was generally similar to clinical chemistry analytes but more pronounced for xenobiotics. Extensive metabolite-metabolite correlations were observed but mainly restricted to within each class. Metabolites were broadly associated with clinical factors, particularly body mass index, sex and renal function. Collectively, our findings inform the conduct and interpretation of metabolite association and precision medicine studies.

Abstract Late presentation to medical care of individuals infected with the human immunodeficiency virus (HIV) is linked to poor outcomes and increased morbidity and mortality. Missed opportunities for a prompt diagnosis are frequently reported among late presenters. We aimed to estimate the proportion of late presenters and missed opportunities in diagnosis among newly diagnosed HIV-positive subjects presenting to a specialty clinic in Lebanon. This is a retrospective chart review of all newly diagnosed adult HIV-positive subjects presenting to clinic from 2012 to 2022. Demographic, laboratory, and clinical data were collected at initial HIV diagnosis or presentation to medical care. We defined late presentation as having a CD4 count

Abstract Local adaptation can increase fitness under stable environmental conditions. However, in rapidly changing environments, compensatory mechanisms enabled through plasticity may better promote fitness. Climate change is causing devastating impacts on coral reefs globally and understanding the potential for adaptive and plastic responses is critical for reef management. We conducted a four-year, three-way reciprocal transplant of the Caribbean coral Siderastrea siderea across forereef, backreef, and nearshore populations in Belize to investigate the potential for environmental specialization versus plasticity in this species. Corals maintained high survival within forereef and backreef environments, but transplantation to nearshore environments resulted in high mortality, suggesting that nearshore environments present strong environmental selection. Only forereef-sourced corals demonstrated evidence of environmental specialization, exhibiting the highest growth in the forereef. Gene expression profiling 3.5 years post-transplantation revealed that transplanted coral hosts exhibited profiles more similar to other corals in the same reef environment, regardless of their source location, suggesting that transcriptome plasticity facilitates acclimatization to environmental change in S. siderea. In contrast, algal symbiont (Cladocopium goreaui) gene expression showcased functional variation between source locations that was maintained post-transplantation. Our findings suggest limited acclimatory capacity of some S. siderea populations under strong environmental selection and highlight the potential limits of coral physiological plasticity in reef restoration.

We isolated Issyk-Kul virus (ISKV) from a bat sampled from Italy in 2021 and conducted ISKV-specific surveillance in bats collected in Italy during 2017–2023. ISKV circulation among synanthropic and sedentary species of bat, such as Savi’s pipistrelle bat (Hypsugo savii) in northern Italy, may have public health implications in this region.