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High-grade soft tissue sarcomas (STS) are a heterogeneous and aggressive set of cancers. Failure to respond anthracycline chemotherapy, standard first-line treatment, is associated with poor outcomes. We investigated the contribution of STS cancer stem cells (STS-CSCs) to doxorubicin resistance. We identified a positive correlation between CSC abundance and doxorubicin IC50. Utilizing patient-derived samples from five sarcoma subtypes we investigated if a common genetic signature across STS-CSCs could be targeted. We identified Enhancer of Zeste homolog 2 (EZH2), a member of the polycomb repressive complex 2 (PRC2) responsible for H3K27 methylation as being enriched in CSCs. EZH2 activity and a shared epigenetic profile was observed across subtypes and targeting of EZH2 ablated the STS-CSC population. Treatment of doxorubicin-resistant cell lines with tazemetostat resulted in a decrease in the STS-CSC population. These data confirm the presence of shared genetic programs across distinct subtypes of CSC-STS that can be therapeutically targeted.

ABSTRACT Background High tibial osteotomy (HTO) is a surgical procedure for treating certain knee conditions. Proper execution of HTO can preserve joint function and delay or avoid the need for total knee replacement. This study compared different 3D printing techniques (fused deposition modeling, selective laser sintering, and direct metal laser sintering) and a navigation system for their suitability in assisting HTO surgeries. Methods Tibial saw‐bones were used as models, and surgical guides and the navigation system were employed during the procedures. Six parameters (planning time, manufacturing time, delivery time, material cost, operation time, and accuracy) were evaluated. One‐way analysis of variance (ANOVA) and t‐test were used for the analysis. Results The results showed that the metal surgical guides had the highest accuracy (angle differences mean, 2.4°) and operation time (mean 9.75 min), followed by plastic guides, classic guides, and the navigation system. The differences in accuracy were attributed to factors like rigidity, melting point, and errors during incisions. Conclusions The study recommended metal surgical guides as the best option for assisting HTO due to their accuracy and operation time. And the results have implications for orthopedic surgeons performing HTO surgeries, as they can use this information to improve postoperative outcomes, such as mechanical axis alignment and quality of life for HTO patients.

Abstract Background In Cameroon, like in many other resource-limited countries, data generated by health settings including morbidity and mortality parameters are not always uniform. In the absence of a national guideline necessary for the standardization and harmonization of data, precision of data required for effective decision-making is therefore not guaranteed. The objective of the present study was to assess the reporting style of morbidity and mortality data in healthcare settings. Methods An institutional-based cross-sectional study was carried out from May to June 2022 at the Yaoundé Central Hospital. A questionnaire was used to assess the need to set up a standard tool to improve the reporting system. Medical records were used to collect mortality and morbidity data which were then compared to the International Statistical Classification of Diseases and Related Health Problems-11 (ICD-11) codification. Data were analyzed using IBM-SPSS version 26. Results Out of 200 patients’ morbidity causes recorded, nearly three-quarter (74.0%) were heterogeneous, and two over five (41.0%) of mortality causes reported were also heterogeneous. Most of respondents stated the need to set up a standard tool for collecting mortality and morbidity data (83.6%). Less than one-fifth (18.2%) of health care providers were able to understand data flow, correctly archived data (36.6%) and used electronic tools for data quality control (40.0%). Conclusion There were high levels of heterogeneities of morbidity and mortality causes among patients admitted to the Yaoundé Central Hospital in 2021. It is therefore urgent that Cameroon national health authorities implement the ICD-11 to allow the systematic recording, analysis, interpretation and comparison of mortality and morbidity data collected in Yaoundé Central Hospital at different times; and ensure interoperability and reusability of recorded data for medical decision support.

Abstract High-grade soft tissue sarcomas (STS) are a heterogeneous and aggressive set of cancers. Failure to respond anthracycline chemotherapy, standard first-line treatment, is associated with poor outcomes. We investigated the contribution of STS cancer stem cells (STS-CSCs) to doxorubicin resistance. We identified a positive correlation between CSC abundance and doxorubicin IC50. Utilizing patient-derived samples from five sarcoma subtypes we investigated if a common genetic signature across STS-CSCs could be targeted. We identified Enhancer of Zeste homolog 2 (EZH2), a member of the polycomb repressive complex 2 (PRC2) responsible for H3K27 methylation as being enriched in CSCs. EZH2 activity and a shared epigenetic profile was observed across subtypes and targeting of EZH2 ablated the STS-CSC population. Treatment of doxorubicin-resistant cell lines with tazemetostat resulted in a decrease in the STS-CSC population. These data confirm the presence of shared genetic programs across distinct subtypes of CSC-STS that can be therapeutically targeted.

Abstract Cancer-associated Fibroblasts (CAFs) have emerged as critical regulators of anti-tumour immunity, with both beneficial and detrimental properties that remain poorly characterised. To investigate this, we performed single-cell and spatial transcriptomic analysis, comparing head & neck squamous cell carcinoma (HNSCC) subgroups, which although heterogenous, can be considered broadly immune-hot and immune-cold (human papillomavirus [HPV]+ve and HPV-ve tumours respectively). This identified six fibroblast subpopulations, including two with immunomodulatory gene expression profiles (IL-11 + inflammatory [i]CAF and CCL19 + fibroblastic reticular cell [FRC]-like). IL-11 + iCAF were spatially associated with inflammatory monocytes and regulated in vitro through synergistic activation of canonical NF-κB signalling by IL-1β and TNF-α. FRC-like were enriched in immune-hot HPV+ve tumours, associated with CD4 + T-cells and B-cells in tertiary lymphoid structures and regulated through non-canonical NF-κB signalling via lymphotoxin. Pan-cancer analysis revealed several ‘iCAF’ subgroups present in both normal and cancer tissues; IL11 + iCAF were found in cancers from the gastrointestinal (GI) tract and transcriptomically distinct from iCAFs previously described in pancreatic and breast cancers with greater inflammatory properties; FRC-like fibroblasts were present at low frequencies in all tumour types, and were associated with significantly better survival in patients receiving checkpoint immunotherapy. This work clarifies and expands current literature on immunomodulatory CAFs, highlighting links with important immunological niches.

Background The WHO and Ethiopia’s Ministry of Health have developed strategies to expand and integrate services for co-endemic neglected tropical diseases (NTDs) which manifest in the skin. To inform these strategies, we aimed to understand the social, economic and health system context of skin NTD care in Kalu woreda, Amhara region, Ethiopia, where cutaneous leishmaniasis (CL) and leprosy are endemic.Methods Between October 2020 and May 2022, we surveyed and reviewed records of 41 primary healthcare facilities and explored common disease experiences in focus group discussions (n=40) and interviews with people affected by leprosy (n=37) and CL (n=33), health workers (n=23), kebele authorities and opinion leaders (n=33) and traditional healers (n=7). Opportunities for integrated skin NTD service provision were explored through policy document review, interviews with health officials (n=25), and stakeholder meetings.Results Availability of diagnostic supplies and health worker competence to provide skin care was very limited across primary healthcare facilities, particularly for CL. People with leprosy commonly sought care from healthcare facilities, while people with CL administered self-care or sought help from traditional healers. Travel and costs of care at specialised facilities outside the district inhibited timely care-seeking for both diseases. Transmission discourses shaped different understandings of who was affected by leprosy and CL and expectations of behaviour during and after treatment. Many policy actors felt that existing supply chain interventions, decentralised treatment approaches and community engagement initiatives for leprosy could also benefit CL, but others also warned against increasing care-seeking unless CL treatment could be provided on a scale commensurate with the large burden they perceived.Conclusion Our findings demonstrate significant gaps in the provision of care for skin NTDs within primary healthcare, very different health-seeking patterns for leprosy and CL, and a need to develop new models of care, especially for CL.

BackgroundAntiretroviral treatment increases the risk of accumulation of resistance mutations that negatively impact the possibilities of future treatment. This study aimed to present the frequency of HIV-1 antiretroviral resistance mutations and the genetic diversity among children with virological failure in five pediatric care facilities in Benin.MethodsA cross-sectional study was carried out from November 20, 2020, to November 30, 2022, in children under 15 years of age who failed ongoing antiretroviral treatment at five facilities care in Benin (VL > 3log10 on two consecutive realizations three months apart). Viral loads were measured using the m2000 RealTime Abbott platform. Genotyping was carried out with the commercial Viroseq kit. Sequences were read on the ABI 3500 sequencer and then edited with ViroSeqHIVv3.0 software. The HIV drug resistance database at Stanford University was used to identify mutations and viral subtypes were assigned by phylogenetic analyses.ResultsThe HIV-1 pol gene was sequenced in 47 participants with virological failure of antiretroviral treatment. The median age was 120 [Interquartile Range 90-144] months. The prevalent treatment was EFV base regimen (22/47; 46.8%). Median viral load was 4.39 log10 [IQR 3.81-4.86 log10] respectively. Resistance testing was successful among (37/47; 78.72%) children, resistance mutations were detected in (32/37; 86.48%) children, and (29/32; 90.62%) had at least one surveillance drug resistance mutation. Respectively (25/32; 78.12%), (28/32; 87.5%), (4/32; 12.90%), (22/32; 68.75%) had at least one resistance mutation associated with NRTIs, NNRTIs, PIs and NNRTIs+NRTIs. (12/32; 37.5%) of children carried mutations related to TAMs. the most frequently NRTIs identified were M184V (21/62; 33.9%) followed by TAMs (20/62; 32.2%) and T69G/D (2/62; 3.2%)s. Among mutations associated with NNRTIs K103N represented (18/64; 28.1%) followed by P225H (7/64; 10.9%). The I54V (3/6; 50%) mutation is the major PI observed. Genetic diversity is characterized by a preponderance of CRF02_AG (72%, 23/32), followed by unique recombinant forms (URFs) (25%, 8/32) and one subtype G.ConclusionA high rate of mutations has been observed in children. These data underline the importance of implementing routine genotypic testing in the biological monitoring of infected children to anticipate the accumulation of resistance mutations and thus compromise the treatment options available in Benin.

Abstract BackgroundWomen and sexual minority individuals have been found to be at higher risk for experiencing poor sleep health compared to their counterparts. However, research on the sleep health of sexual minority women (SMW) is lacking in China. ObjectiveThis study aimed to examine sleep quality and social support for Chinese women with varied sexual identities, and then investigate the in-depth relationships between sexual identity and sleep. MethodsThis was a cross-sectional web-based survey. All participants completed a structured questionnaire containing a set of sociodemographic items referring to the social-ecological model of sleep health, the Pittsburgh Sleep Quality Index, the Social Support Rating Scale, and social relationships and environment domains of the World Health Organization Quality of Life-abbreviated short version. Pearson correlation coefficients were used to examine the relationship between sleep quality and social support as well as the two domains of quality of life. Structural equation modeling analysis was used to explore the social-ecological relationships. ResultsA total of 250 cisgender heterosexual women (CHW) and 259 SMW were recruited from July to September 2021. A total of 241 (47.3%) women experienced poor sleep quality and the rate was significantly higher in SMW than in CHW (55.2% vs 39.2%, PPr=P ConclusionsSMW experienced poorer sleep quality compared to CHW. Further research is recommended to address the modifiable factors affecting sleep and then implement tailored sleep improvement programs.

Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid gland, typically associated with an indolent course and favourable prognosis. However, although rare, PTC can demonstrate aggressive behaviour, including vascular invasion with extension into major vessels. Intraluminal tumor thrombus involving the great veins, such as the internal jugular vein (IJV), is an uncommon but significant complication. We present the case of a 56-year-old male who was referred to our clinic for evaluation of a right-sided anterior neck mass. Neck ultrasonography revealed a 5.5 x 6.5 cm heterogeneous mass within the right thyroid lobe and a suspected intraluminal thrombus in the right internal jugular vein. Fine-needle aspiration biopsy under ultrasound guidance confirmed the diagnosis of papillary thyroid carcinoma. Subsequent preoperative contrast-enhanced computed tomography (CT) of the neck confirmed the presence of an intraluminal tumours thrombus extending into the right IJV. The patient underwent total thyroidectomy, right modified radical neck dissection, and resection of the involved segment of the IJV. Postoperatively, the patient received radioactive iodine (I-131) ablation therapy. At the one-year follow-up, imaging studies indicated a recurrence of the disease. A review of the literature focusing on vascular involvement in PTC and diagnostic methods for tumours thrombus reveals that, while rare, intraluminal tumor thrombus should be considered in patients with PTC, especially when there is evidence of vascular invasion. Early and accurate preoperative diagnosis using Doppler ultrasonography and/or contrast-enhanced CT is critical for optimal surgical planning and improved prognosis. Given the potential for recurrence, vigilant long-term follow-up is recommended.

BackgroundThe COVID-19 pandemic has catalysed the emergence of digital solutions in all areas of medicine. Our prior study on the digital health related experiences and opinions of Hungarian physicians highlights the crucial role of age in shaping attitudes towards digital health solutions among medical doctors. Our aim was to examine how under 35-year-old Hungarian physicians relate to digital technologies, the advantages and disadvantages they perceive, and how they would like to incorporate these technologies into their everyday medical practice.MethodsAs part of the “E-physicians and E-patients in Hungary” study, we conducted an online representative survey among medical practitioners in Hungary between July 2021 and May 2022 (n = 1,774). The main target group of our research were physicians under 35 years of age: n = 399 (25.3%). Besides descriptive statistical analyses, cluster analysis and binary logistic regression were applied to analyse the digital health related attitudes of the young age group.ResultsOur cluster analysis confirmed that younger doctors perceived more advantages (on average 7.07 items vs. 8.52 items) and disadvantages (on average 4.06 vs. 4.42) of digital health solutions. They also demonstrated greater familiarity with (8.27 vs. 9.79) and use of (1.94 vs. 2.66) a broader spectrum of technologies. Proficiency and active utilization of diverse technologies correlates with a more comprehensive understanding of both pros and cons, as well as a more realistic self-assessment of areas of further improvement. Doctors under 35 years express a notable demand for significantly increased incentives, both in terms of knowledge transfer/training and infrastructure incentives. Multivariate analyses revealed that young doctors, compared to their older counterparts, perceived enhanced patient adherence as one of the greatest benefits of digital health solutions. Additionally, young doctors expect that digital health solutions could reduce burnout.ConclusionOur results underscore the inevitable transformation of the 21st-century physician role: the success of digital health solutions hinges on active patient involvement and management, which requires proper patient education and professional support in navigating the digital space. Digital health solutions can be a bridge between different generations of doctors, where young people can help their older colleagues navigate the digital world.

Abstract BackgroundBreastfeeding is vital for the health and well-being of both mothers and infants, and it is crucial to create supportive environments that promote and maintain breastfeeding practices. ObjectiveThe objective of this paper was to describe the development of a breastfeeding-friendly app called “bfGPS” (HKU TALIC), which provides comprehensive territory-wide information on breastfeeding facilities in Hong Kong, with the goal of fostering a breastfeeding-friendly community. MethodsThe development of bfGPS can be categorized into three phases, which are (1) planning, prototype development, and preimplementation evaluation; (2) implementation and updates; and (3) usability evaluation. In phase 1, a meeting was held with experts, including maternal and child health researchers, app developers, breastfeeding individuals, and health professionals, to discuss the focus and functionality of the breastfeeding app. A prototype was developed, and breastfeeding facilities in various public venues in Hong Kong were assessed using a structured checklist. For the preimplementation evaluation, 10 focus groups and 19 one-on-one interviews were conducted between May 2019 and October 2020 with staff working in public premises (n=29) and breastfeeding individuals (n=29). For phase 2, bfGPS was published on iOS (Apple Inc) and Android (Google) platforms in September 2020. App updates were launched in September 2021 and May 2022 based on the suggestions provided by the participants in the preimplementation evaluation. For the usability evaluation, semistructured, in-depth, one-to-one interviews were conducted with breastfeeding individuals (n=30) to understand their experiences of using bfGPS. Content analysis was used to analyze the data. ResultsbfGPS is a mobile app that was developed to assist breastfeeding individuals in locating breastfeeding facilities in public venues in Hong Kong. In the preimplementation evaluation, the participants gave comments on the layout and interface of bfGPS, and suggestions were given on incorporating new functions into the app. Based on the suggestions of the participants in the preimplementation evaluation, a few additional functions were added into bfGPS, including allowing the users to rate and upload recent information about breastfeeding facilities and an infant tracker function that encourages users to record infant development. In the usability evaluation, 3 main themes emerged—bfGPS improves the community experience for breastfeeding individuals, facilitates tracking the infant’s growth, and provides suggestions for further development. ConclusionsThe bfGPS app is the first user-friendly tool designed to assist users in locating breastfeeding facilities within the community. It stands as a guide for similar health care app developments, emphasizing the importance of accurate, current data to ensure user adoption and long-term use. The app’s potential lies in the support and reinforcement of breastfeeding practices coupled with self-management strategies.

Introduction: Approximately 5.8 million people die each year as a result of injuries. Traumatic injury is the leading cause of death under the age of 45 in the U.S. and worldwide. Traumatic injuries represent a significant global health burden, demanding swift and decisive intervention to mitigate morbidity and mortality. The Advanced Trauma Life Support (ATLS) course has emerged as a cornerstone in trauma management, offering healthcare providers a systematic approach to assessment, resuscitation, and definitive care. This article explores the pivotal role of ATLS protocols as the gold standard for safe and effective trauma management. ATLS protocols prioritize a structured assessment methodology, employing the ABCDE approach to rapidly identify and address life-threatening injuries. By adhering to this systematic framework, healthcare providers can promptly initiate time-critical interventions, minimizing the risk of adverse outcomes. Moreover, ATLS protocols promote standardization of care, ensuring consistent management practices across diverse clinical settings. Through multidisciplinary collaboration and continuous training, healthcare teams are equipped to deliver coordinated and efficient care, optimizing patient outcomes. In conclusion, using ATLS trauma management protocols represents more than a guideline; it embodies a commitment to excellence in patient care. By embracing the principles of ATLS, healthcare providers uphold the gold standard for safe, effective, and compassionate trauma management, ultimately saving lives and restoring hope in times of crisis.

IntroductionEmerging adulthood is a vulnerable period and can be a crisis for many youth, leading to serious mental health problems. Medical students are especially vulnerable due to their high exposure to stressors, requiring enhanced resilience to cope with academic challenges. This study measured the effectiveness of a near-peer mentoring program in terms of resilience.MethodsA non-randomised controlled trial was conducted at Semmelweis University involving 133 medical students. The case group (n = 94) comprised students who participated in a mentoring program as mentors or mentees. The control group (n = 39) did not participate in mentoring. Data was collected at two points, 5 months apart, at the semester’s start (August 2022) and end (February 2023). Self-report measures included sociodemographics, resilience (Connor-Davidson Resilience Scale), and depression (Depression Anxiety and Stress Scale). Statistical analysis involved descriptive statistics and mixed linear models for repeated-measures ANOVA.ResultsResults showed a significant increase in resilience for the case group compared to the control group (F (1, 129) = 5.578, p = 0.020), with no significant main effect of time. There was a significant interaction effect between intervention and time on resilience (F (1.000, 129.000) = 4.915, p = 0.028). Depression scores showed no significant group difference but a significant main effect of time (F (1.000, 129.000) = 4.725, p = 0.032) and the interaction effect between intervention and time on depression (F (1.000, 129.000) = 4.018, p = 0.047).DiscussionThis mentoring program effectively increased resilience and helped maintain mental health, contributing to developing skilled healthcare professionals—where resilience remains a key strength for 21st-century doctors.

BackgroundOrthohantaviruses (also known as hantaviruses) are pathogens, primarily transmitted by rodents, that can cause hemorrhagic fever with renal syndrome (HFRS). In endemic regions of Kazakhstan, no confirmed HFRS cases were detected between 2020 and 2022 raising concerns about detection. Estimate antibody seroprevalence for hantaviruses and identify associated risk factors among high-risk adults in western Kazakhstan in 2023.MethodsIn this cross-sectional study, adults were randomly sampled from public clinic registries in 14 villages in West Kazakhstan during June–July 2023. We interviewed 921 participants and collected serum samples which were tested for presence of hantavirus specific IgG antibodies using enzyme-linked immunosorbent assay (ELISA). Socio-demographic, clinical characteristics, and residential risk-factor data were self-reported. We assessed factors associated with seropositivity using multivariable Poisson regression, adjusting for key variables such as age and gender.ResultsAmong 921 participants, 63.0% were female, median age was 53 years, 72.0% resided in single houses and 38.0% reported encounters with rodents. Among 921 participants we found 3.1% (n = 28) hantavirus seroprevalence (95% confidence interval [CI]: 2.1–4.3). No seropositive participants had prior hospitalization or symptoms consistent with hantavirus. Three seronegative participants had previous hospitalization for hemorrhagic fever with renal syndrome. Over one-third (38%) of participants encountered rodents or droppings in the past year in their homes or workplaces. Higher seroprevalence was found among office occupational workers than unemployed people (prevalence ratio [PR]:7.3, 95%CI: 1.3–53.5), and among those who lived near ponds than those who did not (PR:11.5, 95%CI: 1.6–54.7).ConclusionOverall, the seroprevalence was low, but indicated some risk of infection among the adult population. Our results highlight potential occupational and residential risk factors for hantavirus infection in West Kazakhstan. Relevant public health interventions should include educating the population about promoting preventive practices, workplace hygiene, rodent control measures, and enhanced case diagnosis and management.

Objective: To investigate the effects of oral baricitinib on ocular surface disease (OSD) in patients with chronic graft-versus-host disease (cGVHD). Design: Prospective phase 1 to 2 single institution trial. Subjects: Eighteen patients with ocular graft-versus-host-disease (oGVHD) and systemic steroid-refractory cGVHD. Methods: Oral baricitinib (2 mg and 4 mg) was administered daily for up to 12 months in an intrapatient dose-escalation design. National Institutes of Health (NIH) oGVHD score, vision, corneal Oxford staining (COS), tear break-up time (TBUT), Schirmer I test (ST) without anesthesia, and microliter tear equivalent conversion were assessed at baseline, 6 months (primary efficacy end point), and 12 months if patients remained on the drug. Main Outcome Measures: Improvement in NIH oGVHD score, COS, TBUT, and ST results in patients with and without conjunctival fibrosis at 6 months. Results: At 6 months, the NIH oGVHD score significantly improved (P = 0.014) with all OSD parameters also showing improvement, though not statistically significant. COS baseline, 2.17 to 0.95; TBUT baseline, 6.66 to 8.18 seconds, Schirmer I baseline, 3.86 mm (2.6 μl) to 5.56 mm (3.9 μl). For patients continuing treatment at 12 months improvements persisted compared with the baseline but remained statistically nonsignificant. Corneal Oxford staining decreased to 0.94; TBUT increased to 8.95 seconds, and ST improved to 10.19 mm (7.2 μL). Conjunctival fibrosis was present in 39% (n = 7) of the patients at baseline. The greatest improvement was observed in the 11 patients without prior conjunctival fibrosis compared with the baseline: COS 1.84, TBUT 6.32 seconds, ST 4.07 mm (2.1 μl); 6 months: COS 0.25 (P = 0.018), TBUT 8.62 seconds, ST 9.12 mm (5.4 μl); 12 months: COS 0, TBUT 10.29 seconds, ST 16.88 mm (10.6 μl). Vision was stable in all groups. Two patients developed asymptomatic, self-limited conjunctival papillomas, and 1 patient developed uncomplicated bacterial conjunctivitis twice. No dose limiting toxicity was observed. Severe adverse events with hospitalizations for possible drug-related systemic infections occurred in 5 patients. Conclusions: Systemic baricitinib was well-tolerated, improved NIH oGVHD scores and OSD parameters in patients with oGVHD, with the greatest benefits observed in patients without pre-existing conjunctival fibrosis. Conjunctival fibrosis may affect outcomes and should be considered in patient selection for clinical trials. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.