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A list of diagnosis codes mapped to CDC-defined high-risk conditions for severe COVID-19 outcomes is currently not available in the literature. We reviewed the CDC list of underlying conditions associated with severe COVID-19 and a coding expert and two clinicians mapped the relevant high-risk conditions to the appropriate ICD-10-CM codes. We additionally assessed the prevalence of these conditions in the Optum de-identified-Clinformatics® Data Mart Database and the Optum de-identified Electronic Health Record dataset. A comprehensive list of approximately 8200 codes were mapped to the CDC-defined high-risk underlying conditions; these ICD-10-CM codes were stratified into three groups corresponding with the CDC strength of evidence category (conclusive, suggestive, or mixed evidence). Applying these codes to administrative claims and EHR datasets demonstrated a consistent prevalence of high-risk conditions over four years (2018–2021). These findings present a comprehensive list of codes that can be used by clinicians and researchers to identify and characterize patients at high risk for severe COVID-19 outcomes.

The teaching of English subject in elementary school with the K-13 is not to be so called rare. Many teachers have different perspectives on the curriculum whether it’s the strategies or challenges in the implementation of the teaching process. This study goal is to view the perspective of English teacher interpretation of K-13. This research uses observation checklists and interviews. This study involves 3 English teacher that teaches elementary school to be observed and interviewed. Researchers conducted an observation on one of the teachers while they teach and conducted interview face to face with the 3 teachers. The data that was gathered was then sorted out in the observation checklists and transcription. The results showed that teachers have various teaching methods that they use such as implementing interactive lessons, engaging in group discussion, encouraging students in activity and collaboration, providing opportunities to students, and the use of technology. Meanwhile, challenges in teaching occur such as limitation of teaching resources, large class size, and time limitations. It could be concluded that while teachers implement teaching methods in K-13 teaching, it could still raise some problems for them. The implication of this study is that teachers are supposed to adapt to the curriculum to make a great learning environment.

Bacterial biocontrol agents that antagonize soilborne pathogens are increasingly considered alternatives to chemical pesticides, but their in vivo efficacy is often inconsistent, restricting commercial use. The efficacy of a biocontrol agent can depend on rhizosphere competence and its interaction with native microbiomes, which can affect ecosystem functioning. This study investigated the capacity of a Bacillus cereus sensu lato biocontrol strain (S-25) to persist on roots and in the rhizosphere of cucumber and evaluated its impact on bacterial and fungal community composition in the rhizosphere in the absence and presence of Rhizoctonia solani, the causative agent of damping-off disease in young seedlings. Following amendment, S-25 abundance in the cucumber rhizosphere decreased by two orders of magnitude but remained relatively high for the duration of the experiment, in contrast to the root surface, where it was not detected. Amendment with S-25 significantly reduced the incidence of disease caused by R. solani without reducing the relative abundance of the fungal pathogen. Interestingly, R. solani did not substantially alter the rhizosphere microbial community, whereas S-25 reduced bacterial diversity and facilitated a shift in community composition, with increased relative abundance of Acidobacteriota and Actinomycetota, and reduced abundance of Pseudomonadota, Bacteroidota, and Verrucomicrobiota. Collectively, this study provides important insights into the mode of persistence of biocontrol agents and their effect on native microbiomes in the rhizosphere of pathogen-inoculated plants. It demonstrates that amendment can significantly alter local microbiomes and suggests that optimizing amendment regimes or selecting strains with higher rhizosphere competence can enhance future biocontrol agents.

Abstract Background Stigma and discrimination towards people with mental health conditions by their communities are common worldwide. This can result in a range of negative outcomes for affected persons, including poor access to health care. However, evidence is still patchy from low- and middle-income countries (LMICs) on affordable, community-based interventions to reduce mental health-related stigma and to improve access to mental health care. Methods This study aims to conduct a feasibility (proof-of-principle) pilot study that involves developing, implementing and evaluating a community-based, multi-component, awareness-raising intervention (titled Indigo-Local), designed to reduce stigma and discrimination and to increase referrals of people with mental health conditions for assessment and treatment. It is being piloted in seven sites in five LMICs—China, Ethiopia, India, Nepal and Tunisia—and includes several key components: a stakeholder group workshop; a stepped training programme (using a ‘Training of Trainers’ approach) of community health workers (or similar cadres of workers) and service users that includes repeated supervision and booster sessions; community engagement activities; and a media campaign. Social contact and service user involvement are instrumental to all components. The intervention is being evaluated through a mixed-methods pre-post study design that involves quantitative assessment of stigma outcomes measuring knowledge, attitudes and (discriminatory) behaviour; quantitative evaluation of mental health service utilization rates (optional, where feasible in sites); qualitative exploration of the potential effectiveness and impact of the Indigo-Local intervention; a process evaluation; implementation evaluation; and an evaluation of implementation costs. Discussion The output of this study will be a contextually adapted, evidence-based intervention to reduce mental health-related stigma in local communities in five LMICs to achieve improved access to healthcare. We will have replicable models of how to involve people with lived experience as an integral part of the intervention and will produce knowledge of how intervention content and implementation strategies vary across settings. The intervention and its delivery will be refined to be feasible and ready for larger-scale implementation and evaluation. This study thereby has the potential to make an important contribution to the evidence base on what works to reduce mental health-related stigma and discrimination and improve access to health care.

Betulinic acid (BA) is a natural pentacyclic triterpenoid with significant pharmaceutical potential. We found that converting BA into amino acid ethyl ester salts alters its cytotoxic effect on colorectal adenocarcinoma cells (HT-29). Among these salts, the estimated half-maximal inhibitory concentration (IC50) at 72 h varies by up to fifteenfold. The proline ethyl ester [ProOEt] salt, the most active compound, exhibited an IC50 value of 3.8 µM, which is 4.8 times lower than that of the parent BA. We observed that exposure to BA or [ProOEt][BA] induced apoptosis in HT-29 cells. Additionally, the proline-based salt led to a higher level of IL1B gene expression in PBMCs at a lower stimulation concentration.

Abstract Background Implementation of screening brief intervention and referral to treatment (SBIRT) and medication-assisted treatment for alcohol use disorder (MAUD) remains low in primary care. ANTECEDENT (Partnerships to Enhance Alcohol Screening, Treatment, and Intervention) was a practice-facilitator led implementation study to increase SBIRT and MAUD use in diverse primary care clinics. Methods From November 2019 – April 2023, we conducted a convergent parallel mixed methods evaluation. Participants were small and medium-sized primary care clinics in the Northwestern U.S. Clinics received foundational support (i.e., baseline/exit assessment, access to SBIRT Oregon website) and the option for supplemental implementation support (e.g., practice facilitation, expert consultation) over the 15-month intervention to improve SBIRT and MAUD. Qualitative and quantitative data regarding clinic characteristics, implementation strategies, and SBIRT/MAUD outcomes were collected through practice facilitator interviews, periodic reflections and clinic contact logs, interviews, pre-post surveys, and electronic health record (EHR) queries. Quantitative analyses included descriptive statistics, logistic regression, and the Wilcoxon sign-ranked test. Qualitative analysis took an immersion crystallization approach. Data were reviewed in a matrix to evaluate intervention adoption, implementation, and effectiveness. Results We recruited 75 unique clinics; 66 participated and 48 (73%) completed the study. Eight participating clinics chose to receive foundational support only (12%) while 58 chose to engage in supplemental support (88%) activities. Clinics that received supplemental support and completed the intervention (n = 42) engaged in practice facilitation (Mean: 293 min, range: 75–550 min); data review (38%), HIT support (31%), expert consultation (19%), and peer-to-peer learning (5%). Pre- and post-intervention assessments showed significant improvement in self-reported SBIRT process outcomes. Performance data improved among the subset of completing clinics able to produce data (n = 17). Clinics described positive experiences with ANTECEDENT support and highlighted remaining barriers to SBIRT and MAUD implementation. Conclusions Participating clinics engaged in a diverse range of supportive activities. A flexible approach using practice facilitation and implementation support could be helpful for low-resourced primary care clinics in improving SBIRT and MAUD for unhealthy alcohol use.

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 Background Approximately 15% of pediatric firearm injuries are unintentional. While demographic characteristics of unintentional firearm injuries have been described, the relationship between injury characteristics and mortality is not well understood. In this study, we identified injury characteristics associated with fatality among unintentional firearm injuries in adolescents. Methods We conducted a retrospective (May 2022-May 2023) cross-sectional study of unintentional firearm injuries among adolescents 12–17 years old using the Gun Violence Archive. Variables included victim age and sex, shooter age and sex, injury location, injury circumstance, number of firearms, type of firearm, firearm owner, census region, and shooter relationship to the victim. Logistic regression was used to identify variables associated with fatality. Results Of 319 unintentional incidents, 212 (66.5%) were non-fatal and 107 (34.5%) were fatal. Of all shootings, 176 (55.2%) occurred in a residence. A shooter was identified in 256 (80.3%) cases; 43.0% of these were a peer of the victim. The adjusted odds of fatality were higher when a peer was the shooter (aOR 5.38, 95% CI 2.57, 11.80) compared to self-inflicted injury and when the shooting took place in the victim’s residence (aOR 2.87, 95% CI 1.07, 7.88) or another residence (aOR 3.03, 95% CI 1.45, 6.67) versus a public location (Fig. 1). Conclusions Unintentional firearm injuries were more likely fatal when a peer was the shooter and when the shooting occurred at a residence. This amplifies the importance of safe home firearm storage and exploring other evidence-based approaches to decreasing youth access to firearms.

Abstract Background Language and cultural discordance refer to when a physician and patient do not share the same language or culture. This can create barriers to providing high-quality care at the end-of-life (EoL). This study explores the intersections of language, culture, geography, and care model in EoL care from the perspectives of palliative care physicians. Methods In this exploratory-descriptive qualitative study, semi-structured interviews (1-h) were conducted virtually between July and November 2023. We interviewed 16 family physicians with experience providing linguistic and/or culturally discordant palliative/EoL care in various urban, suburban, and rural regions of Ontario, who practiced at community and hospital outpatient clinics, home-based care, or long-term care homes. We used reflexive thematic analysis to identify themes across the interviews guided by the intersectionality theoretical framework. Results We identified three themes 1) Visible barriers to care access due to the inability to communicate accurate information and insufficient time spent during appointments with patients; 2) Invisible barriers to care access, shaped by the Eurocentric approach to palliative care and physicians’ lack of awareness on cultural discordance; 3) Workplace supports that currently exist and interventions that physicians would like to see. Community physicians following fee-for-service models were less likely to have access to professional interpreter services. Physicians in long-term care emphasized resource limitations to providing culturally-appropriate care environments. Conclusion Cultural discordance required awareness of personal biases, while language discordance hindered basic communication. These findings will be useful in informing clinical practice guidelines and mobilizing policy-level change to improve palliative/EoL care for patients from linguistic and cultural minority groups.

Abstract Background Urethral obstruction is a common and life-threatening condition in male small ruminants. Case presentation This case report describes a 3-year old 103 kg Zwartbles breeding ram, presented with the complaint of straining, suspected to have an urethral obstruction. The work-up included clinical examination, laboratory analyses, ultrasound imaging, (contrast) radiography and urine examination. At presentation, blood analysis revealed a respiratory alkalosis, hyperkalaemia and mild azotaemia. On transabdominal ultrasound an enlarged bladder (diameter 11 cm) and free fluid surrounding the right kidney were observed. Treatment of the animal included tube cystostomy, intravenous perfusion, antimicrobial treatment, ammonium chloride and NSAIDs. No indications for urolithiasis were found on ultrasound, radiography, or urine examination. As no improvement was seen despite 16 days of therapy, a contrast radiograph of the urinary tract, as well as reproductive exam were conducted. Positive anterograde urethrogram showed a contrast filled cavitary lesion at the caudal aspect of the pelvic urethra. The reproductive ultrasonography revealed the same large urethral distention or abscess compressing the pelvic urethra, as well as severe testicular degeneration in both testis. The results of the contrast radiograph and the reproductive exam lead to the decision to euthanize the animal, as the animal would not be capable of breeding. Computed tomography was performed post-mortem, which showed close relation between the cavitary lesion and the left bulbourethral gland. Pathology revealed a lymphoplasmacytic to suppurative infection at the level of the urogenital tract, chronic interstitial nephritis and a perirenal to cortical abscess of the right kidney as well as a periurethral abscess. As for the reproductive system, multifocal interstitial inflammatory infiltrates were seen on the entire system. Marked fibrosis and atrophy was seen at the level of the testes and both epididymides. Conclusions A periurethral abscess should be included in the differential diagnosis for an urethral obstruction in small ruminants. The extensive medical imaging, together with the ante-mortem and post-mortem findings, makes this a good reference case for diagnosticians confronted with urethral problems in a ram.

Abstract Objective To evaluate implementation of a patient decision aid for symptomatic uterine fibroid management to improve shared decision-making at five clinical settings across the United States. Methods We used a type 3 hybrid effectiveness-implementation stepped-wedge design and the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) planning and evaluation framework. We conducted clinician training, monthly reach tracking with feedback to site clinical leads, patient and clinician surveys, and visit audio-recordings. Implementation strategies included assessment of organizational readiness for shared decision-making, synchronous clinician training, audit and feedback of decision aid reach, and access to multiple decision aid formats. Outcomes and analyses included patient-level reach, clinician-level adoption, and associations of patient-reported decision aid exposure (as treated) and setting-level implementation (intention-to-treat) with patient-reported (collaboRATE measure) and observed (OPTION-5 measure) shared decision-making. We also designed and assessed setting-level plans for sustainability and other factors impacting sustained decision aid use. Results The decision aid was adopted by 72 of the 74 eligible gynecologists (97%) and reached 2553 patients across five settings. CollaboRATE scores improved among patients who reported receiving the decision aid (as-treated analysis, 69% vs. 59%; OR 1.6, 95% CI 1.16–2.27). CollaboRATE scores remained consistent before and after setting-level decision aid implementation (intention-to-treat analysis, 64% vs. 63%; OR 0.86, 95% CI 0.61–1.22). Participants would prefer to receive a decision aid at multiple time points (91.9% before the visit, 90.7% during the visit, 86.5% after the visit). Shared decision-making experiences did not improve when comparing pre vs. post-implementation collaboRATE scores across included settings (intention-to-treat, 64% vs. 63%; OR 0.86, 95% CI 0.61–1.22). Conclusion When patients with symptomatic uterine fibroids are given decision aids, they report higher shared decision-making scores. However, the differences we observed between the as-treated and intention-to-treat results suggest that unaddressed implementation challenges continue to limit the extent to which patients receive decision aids and likely hinder their overall impact. Future efforts to implement decision aids should explore enhancing their integration into clinical workflows and standard operating procedures, supported by organizational incentives that prioritize shared decision-making. Trial registration ClinicalTrials.gov NCT03985449; registered 6 June 2019.

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.

Abstract Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and in some cases, the same Ig-heavy chains. The current trial-and-error search for immunogen modifications that improve selection for specific bnAb mutations is imprecise. Here, to precisely engineer bnAb boosting immunogens, we use molecular dynamics simulations to examine encounter states that form when antibodies collide with the HIV-1 Envelope (Env). By mapping how bnAbs use encounter states to find their bound states, we identify Env mutations predicted to select for specific antibody mutations in two HIV-1 bnAb B cell lineages. The Env mutations encode antibody affinity gains and select for desired antibody mutations in vivo. These results demonstrate proof-of-concept that Env immunogens can be designed to directly select for specific antibody mutations at residue-level precision by vaccination, thus demonstrating the feasibility of sequential bnAb-inducing HIV-1 vaccine design.

Abstrak: Kemampuan regulasi emosi sangat dibutuhkan bagi siswa. Dengan memiliki regulasi emosi yang baik, remaja dapat mengelola emosi negatif dan berperilaku dengan cara yang dapat diterima oleh orang lain, dapat mengatasi perasaan sedih, kecewa, dan putus asa sehingga dapat menghindari terjadinya depresi. Tugas utama Bimbingan dan Konseling yaitu memberikan layanan bantuan kepada peserta didik untuk mencapai perkembangan dirinya secara optimal. Salah satu media dalam pemberian layanan yang diharapkan dapat menciptakan suasana yang menarik dan kondusif yaitu dengan penggunaan media flash flipbook. Dalam penelitian ini menggunakan metode research and development (RnD) model Borg & Gall yang meliputi 7 langkah. Penelitian ini dilakukan di kelas SMA 1 Batujajar dengan melibatkan 38 siswa. Berdasarkan hasil validasi ahli materi diperoleh hasil penilaian memiliki skor rata-rata sebesar 79,3% dan termasuk kategori layak. Berdasarkan validasi ahli media diperoleh hasil rata-rata sebesar 89% dan termasuk kategori sangat layak. Berdasarkan hasil validasi dari ahli praktisi diperoleh skor rata-rata sebesar 87,7% dan termasuk kategori sangat layak. Hasil persentasi dari pemahaman siswa terkait regulasi emosi dapat dikategorikan Paham dengan rata-rata sebesar 58%, sehingga Ini membuktikan bahwa media flash flipbook layak digunakan dalam meningkatkan keterampilan regulasi emosi siswa. Abstract: Emotional regulation skills are very necessary for students. By having good emotional regulation, teenagers can manage negative emotions and behave in a way that is acceptable to others, can overcome feelings of sadness, disappointment and despair so that they can avoid depression. The main task of Guidance and Counseling is to provide assistance services to students to achieve optimal personal development. One of the media in providing services that is expected to create an attractive and conducive atmosphere is the use of flash flipbook media. In this research, the Borg & Gall model of research and development (RnD) method is used, which includes 7 steps. This research was conducted in the class of SMA 1 Batujajar involving 38 students. Based on the validation results from material experts, the assessment results showed that the average score was 79.3% and was included in the feasible category. Based on media expert validation, the average result was 89% and was included in the very feasible category. Based on validation results from expert practitioners, an average score of 87.7% was obtained and was included in the very feasible category. The percentage results of students' understanding regarding emotional regulation can be categorized as Understanding with an average of 58%, so this proves that the flash flipbook media is suitable for use in improving students' emotional regulation skills.

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 Peripartum cardiomyopathy (PPCM) is a form of heart failure occurring towards the end of pregnancy or in the months following delivery. Concerns regarding the role of prolactin (the polypeptide hormone responsible for lactation) driving the pathogenesis of PPCM have led experts to discourage patients from breastfeeding; however, limited clinical data exist. We sought to (1) determine whether lactation was associated with less cardiac recovery and (2) assess the counseling about breastfeeding given to patients at the time of their initial diagnosis. Methods Patients diagnosed with PPCM from 1999 to 2019 were identified through detailed chart review and demographic characteristics, comorbidities, outcomes, and lactation status were collected. Cardiac recovery was defined as left ventricular ejection fraction (LVEF) 55% or higher. A survey about breastfeeding and patient experience was administered by mail. Patients were only included in this analysis if definitive information about lactation status was documented. Results Of 220 patients with confirmed PPCM, lactation status was known definitively in 54 patients; of these, 18 (33%) had breastfed for at least 6 weeks and 36 (67%) did not breastfeed. There were no significant differences in the breastfeeding and non-breastfeeding groups related to baseline LVEF, age, race, gestational diabetes, smoking, hypertensive disorders of pregnancy, and medication treatments. Despite similar baseline LVEF at the time of diagnosis, there was no statistically significant difference in cardiac recovery based on lactation status. In a subset of patients with severe cardiac dysfunction at the time of diagnosis, there remained no significant differences in recovery based on lactation status. Of the 34 survey respondents, 62% were told not to breastfeed due to their diagnosis or concerns regarding safety of medications, and none were encouraged to breastfeed. Conclusion In this retrospective cohort, lactation was not associated with lower rates of myocardial recovery. Importantly, a majority of patients had received counseling that they should not breastfeed. Future studies of the role of lactation in PPCM are needed in order to better understand the impact of breastfeeding and improve patient counseling.

Abstract Background Antibiotic resistance in uropathogens has rapidly escalated over time, complicating treatment and increasing morbidity and mortality. Few studies have explored how the social determinants of health may be associated with patients’ risks for acquiring antibiotic-resistant (AR) uropathogens. Methods We identified urine cultures collected from outpatients presenting to Tufts Medical Center Primary Care Practices between 2015 and 2020. Specimens were included if patients’ age, sex, and residential address were recorded in the electronic medical record (EMR) and if their urine culture yielded Enterococcus spp. or one or more gram-negative bacterial organism(s) or for which antibiotic susceptibility profiling and species identification was conducted. We abstracted patients’ sociodemographic characteristics from the EMR and used US Census Bureau data to identify characteristics about patients’ census tracts of residence. We evaluated associations between individual- and neighborhood-level characteristics and patients’ risk of having a urine culture resistant to (1) three or more antibiotic classes (i.e., multidrug resistant [MDR]), (2) first-line treatments, (3) fluoroquinolones, (4) aminoglycosides, or (5) ceftriaxone using logistic regression models and a Bonferroni correction to account for multiple hypothesis testing. Results We included urine cultures from 1,306 unique outpatients, most of whom were female (89%). Patients largely self-identified as Non-Hispanic White (36%), Asian (15%), or Non-Hispanic Black (11%). Over 60% lived in an environmental justice-designated census tract. Most included isolates were Escherichia coli (76%) or Klebsiella pneumoniae (7%). Using public insurance increased patients’ odds of having a uropathogen resistant to first-line antibiotics, but living in a limited-income neighborhood reduced patients’ odds of having a MDR uropathogen by 47%. We noted a strong but non-significant positive trend between speaking a language other than English and having an aminoglycoside-resistant uropathogen (p-value = 0.02). Most notably, after controlling for other factors, we observed no statistically significant associations between race or ethnicity and AR uropathogens. Conclusion The social determinants of health may play important and intersecting roles in determining a patient’s risk of having a resistant uropathogens that is more challenging or expensive to treat. It is crucial to acknowledge how race is likely to be a proxy for other factors affecting health, and to consider that some groups may be disproportionately impacted by antibiotic resistance.

Abstract Large-scale anticyclonic vortices forming along the Gulf of Alaska continental slope serve as fertile ecosystems for marine life, significantly shaping the distribution of primary productivity, with 40–80% of the gulf’s open ocean surface chlorophyll-a concentrated in their cores. Between 2013 and 2023, Alaska experienced some of the largest and longest marine heatwaves ever recorded in the world’s oceans, persistently altering its ecosystem and fisheries. Here, using 30 years of satellite and reanalysis data, we find that the coastal upwelling atmospheric forcing conditions associated with the heatwaves have also significantly suppressed the Gulf of Alaska’s ocean circulation and the formation of large anticyclones. Climate model simulations spanning from 1850 to 2100 suggest that future changes in the Aleutian Low pressure system will lead to a 60% increase in upwelling extremes (>2 standard deviations), further weakening the ocean anticyclones. However, large uncertainties remain in the mechanisms controlling the Aleutian Low’s response to climate forcing in the models.

Background: Insomnia is common in patients with psychiatric disorders. However, patients’ awareness of sleep has seldom been examined in detail. In this study, we investigated sleep awareness in outpatients at the psychiatry department of a university hospital. Methods: The participants (n = 241) were recruited at the psychiatry department of Ehime University Hospital between 11 October and 5 November 2021. The following questionnaires were used: Clinical Global Impression Scale of Severity (CGI-S), Global Assessment of Functioning (GAF), General Health Questionnaire (GHQ-30), Athens Insomnia Scale (AIS), and Epworth Sleepiness Scale (ESS). Psychiatric disorders were diagnosed by certified psychiatrists using the International Statistical Classification of Diseases and Related Health Problems 10. Participants with an AIS score of ≥6 were allocated to the insomnia group for statistical analysis. A logistic regression analysis was conducted to identify which items of sleep hygiene the patients with insomnia practiced using the Sleep Guidelines for Health Promotion. Results: Of 241 participants, 133 (55.2%) were allocated to the insomnia group. The mean scores for the CGI were significantly higher and the GAF scores were significantly lower in the insomnia group than in the healthy sleep group (p < 0.01). Of the 12 sleep guidelines proposed by the Japanese Government, “Do not go to bed until you are sleepful, do not delay getting up”, was the item that maximally influenced insomnia. Conclusions: The insomnia group had worse scores on various medical assessment scales compared to the healthy sleep group. Based on a survey of outpatients at the psychiatry department of the university hospital, appropriate stimulus control techniques may help clinicians to treat outpatients with insomnia.

The pathogenesis of many diseases, such as obesity, depression, cancer, cataract, and neurodegenerative diseases, is related to the generation of reactive oxygen species (ROS). Structures possessing radical-scavenging properties act as antioxidants and they could prevent the progression of the aforementioned diseases. Therefore, the current work was focused on the resynthesis and the antioxidant evaluation of 13 hydrazide-hydrazones. Two in vitro tests - DPPH and ABTS, were applied for the determination of the antioxidant capacities. The free-radical scavenging assays displayed that the hydrazide-hydrazone synthesized after condensation with a salicylaldehyde (5b) is the most potent antioxidant. The in vitro evaluation through the ABTS test showed that the former structure has greater antioxidant properties compared with the used standard - Trolox (6-Hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid). In concentrations of 31 µM, the pyrrole-based structure showed 35.77% radical-scavenging effects. A possible binding conformation of the most active hydrazide-hydrazone in the active site of NADPH oxidase was visualised through docking simulations. The active amino acids involved in the stabilisation of the complexes were discussed. DFT studies demonstrated that 5b is a stable structure with good hydrogen and electron donating properties. Overall, the pyrrole-based hydrazide-hydrazone possesses promising antioxidant properties, however further in vitro/in vivo biological evaluations are required.

Over the last decade, access to global data has become increasingly critical for research, allowing insights into diverse biological, environmental and societal questions at a macro scale. Digitisation has greatly enhanced the use of herbarium data in the analysis of species distributions and ecological niche modelling. Yet, sources on modelling and mapping methodology using open-source software is greatly lacking for beginners. We have created a replicable and thorough tutorial to visualise species occurrence data and exploratory analysis that was developed by undergraduates with broad backgrounds and levels of experience. This tutorial integrates the open-source programmes QGIS, MaxEnt and R to develop distribution maps, using bryophytes as a case study, to promote the accessibility of open-source software and remote access learning. This tutorial has already set the foundation for further research into distribution modelling of rare Illinois bryophytes to better understand the potential impact of climate change.

Two rehydration protocols currently exist to treat diabetic ketoacidosis (DKA) in pediatric patients aged

Abstract NKG2D is a central activating receptor involved in target recognition and killing by Natural Killer and CD8+ T cells. The known role of NKG2D is to recognize a family of self-induced stress ligands that are upregulated on stressed cells such as cancerous or virally infected cells. Fungal pathogens are a major threat to human health, infecting more than a billion patients yearly and becoming more common and drug resistant. Here we show that NKG2D plays a critical role in the immune response against fungal infections. NKG2D can recognize fungal pathogens from most major families including Candida, Cryptococcus and Aspergillus species, and mice lacking NKG2D are extremely sensitive to fungal infections in models of both invasive and mucosal infections, making NKG2D an anti-fungal pattern recognition receptor.

Abstract Background Breast cancer (BC) is the most common cancer in women and incidence rates are increasing; metabolomics may be a promising approach for identifying the drivers of the increasing trends that cannot be explained by changes in known BC risk factors. Methods We conducted a nested case–control study (median followup 6.3 years) within the New York site of the Breast Cancer Family Registry (BCFR) (n = 40 cases and 70 age-matched controls). We conducted a metabolome-wide association study using untargeted metabolomics coupling hydrophilic interaction liquid chromatography (HILIC) and C18 chromatography with high-resolution mass spectrometry (LC-HRMS) to identify BC-related metabolic features. Results We found eight metabolic features associated with BC risk. For the four metabolites negatively associated with risk, the adjusted odds ratios (ORs) ranged from 0.31 (95% confidence interval (CI): 0.14, 0.66) (L-Histidine) to 0.65 (95% CI: 0.43, 0.98) (N-Acetylgalactosamine), and for the four metabolites positively associated with risk, ORs ranged from 1.61 (95% CI: 1.04, 2.51, (m/z: 101.5813, RT: 90.4, 1,3-dibutyl-1-nitrosourea, a potential carcinogen)) to 2.20 (95% CI: 1.15, 4.23) (11-cis-Eicosenic acid). These results were no longer statistically significant after adjusting for multiple comparisons. Adding the BC-related metabolic features to a model, including age, the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk score improved the accuracy of BC prediction from an area under the curve (AUC) of 66% to 83%. Conclusions If replicated in larger prospective cohorts, these findings offer promising new ways to identify exposures related to BC and improve BC risk prediction.

Kuhli loach (Pangio kuhlii) a popular ornamental freshwater fish species with economic potential, originating from Sumatra, Kalimantan, Java, and Malaysia. The kuhli loach's appeal lies in its vibrant colors and distinctive eel-like body. This study aims to explores the sexual primary and secondary characteristics of the kuhli loach. Conducted at Universitas Airlangga in Banyuwangi, Indonesia, the study involved a thorough analysis of 50 kuhli loaches, evenly split between males and females. Morphological observations revealed significant differences (p < 0.05), such as the elongated body and expanded abdominal region in females, suggesting adaptations for reproduction. Internal examinations, including peritoneal dissections and histological analysis, unveiled distinct stages of spermatogenesis in males and ovarian development in females, providing insights into the reproductive cycle. Meristic and morphometric analyses identified noteworthy differences in pectoral fin rays, suggesting potential roles in reproductive behavior, while other traits exhibited similarity between genders. This study contributes to the understanding of kuhli loach ecology and reproductive biology, highlighting the importance of addressing sustainability concerns arising from the continuous exploitation of wild populations. This study serves as a foundational step towards advancing reproductive improvement in fish and supports the conservation of this unique ornamental fish species, with implications for aquaculture practices and economic considerations.

Abstract The intensive nutrient requirements needed to sustain T cell activation and proliferation, combined with competition for nutrients within the tumor microenvironment, raise the prospect that glucose availability may limit CAR-T cell function. Here, we seek to test the hypothesis that stable overexpression (OE) of the glucose transporter GLUT1 in primary human CAR-T cells would improve their function and antitumor potency. We observe that GLUT1OE in CAR-T cells increases glucose consumption, glycolysis, glycolytic reserve, and oxidative phosphorylation, and these effects are associated with decreased T cell exhaustion and increased Th17 differentiation. GLUT1OE also induces broad metabolic reprogramming associated with increased glutathione-mediated resistance to reactive oxygen species, and increased inosine accumulation. When challenged with tumors, GLUT1OE CAR-T cells secrete more proinflammatory cytokines and show enhanced cytotoxicity in vitro, and demonstrate superior tumor control and persistence in mouse models. Our collective findings support a paradigm wherein glucose availability is rate limiting for effector CAR-T cell function and demonstrate that enhancing glucose availability via GLUT1OE could augment antitumor immune function.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease characterized by complex metabolic rewiring that enables growth in changing nutrient availability and oxygen conditions. Transcriptome-based prognostic PDAC tumor subtypes, known as ‘basal-like’ and ‘classical’ subtypes are associated with differences in metabolic gene expression including genes involved in glycolysis. Tumor subtype-specific metabolism phenotypes may provide new targets for treatment development in PDAC, but their functional relevance has not been fully elucidated. We aimed to investigate differences in metabolic profiles and transcriptomes in tumor models derived from patients with basal-like and classical tumors. Methods Patient-derived organoids (PDOs) were established from tumor biopsies collected from patients with metastatic PDAC, including three PDOs from basal-like and five PDOs from classical tumors. Metabolic analyses included assessment of differences in metabolic activity using Seahorse Glycolysis and Mito Stress tests and 13C-glucose metabolites tracing analysis. In order to investigate the influence of mitochondrial pyruvate transport on metabolic differences, PDOs were treated with the mitochondrial pyruvate carrier 1 (MPC1) inhibitor UK-5099. Prognostic relevance of MPC1 was determined using a tumor tissue microarray (TMA) in resectable, and proteomics profiling in metastatic PDAC datasets. Whole genome and transcriptome sequencing, differential gene expression and gene set enrichment analyses were performed in PDOs. Results Metastatic PDAC PDOs showed subtype-specific differences in glycolysis and oxidative phosphorylation (OXPHOS). Basal-like tumor-derived PDOs had a lower baseline extracellular acidification rate, but higher glycolytic reserves and oxygen consumption rate (OCR) than classical tumor-derived PDOs. OCR difference was eliminated following treatment with UK-5099. In the 13C-glucose metabolites tracing experiment, a basal-like tumor PDO showed lower fractions of some M + 2 metabolites but higher sensitivity to UK-5099 mediated reduction in M + 2 metabolites than a classical tumor PDO. Protein level analyses revealed lower MPC1 protein levels in basal-like PDAC cases and association of low MPC1 levels with clinicopathologic parameters of tumor aggressiveness in PDAC. PDO differential gene expression analyses identified additional subtype-specific cellular pathways and potential disease outcome biomarkers. Conclusions Our findings point to distinct metabolic profiles in PDAC subtypes with basal-like tumor PDOs showing higher OXPHOS and sensitivity to MPC1 inhibition. Subtypes-specific metabolic vulnerabilities may be exploited for selective therapeutic targeting.

Abstract Background A minority of people who need alcohol treatment receive it. Unhealthy alcohol use is common among people with HIV (PWH) and can lead to negative health outcomes. The aims of this multi-methods study are to (1) quantitatively describe the prevalence, psychosocial characteristics, and demographic traits of a sample of PWH currently receiving HIV care in Florida who had a self-reported need for alcohol treatment but did not seek care and (2) qualitatively explore reasons why PWH did not seek treatment. Methods PWH enrolled in the Florida Cohort Study between October 2020 and February 2023 who had drinking history (N = 487) completed a cross-sectional survey that asked if there was a time when they recognized they needed help for their drinking but did not seek it. If yes, they were asked an open-ended follow-up question about reasons why they did not seek care. Demographic and behavioral differences between those who did and did not endorse a time when they needed alcohol treatment were determined using multivariable logistic regression, while qualitative data were analyzed with thematic analysis based in the Social-Ecological Model to assess reasons for not seeking care at the individual, social, and systems levels. Results A quarter of PWH (n = 129) with lifetime drinking indicated a time they needed care but did not seek it. Patients who endorsed a time where they perceived the need for treatment but did not seek it were more likely to endorse current at-risk drinking and a history of ever trying to reduce their drinking or formally seek professional alcohol treatment. The most common reasons participants did not seek care were individual level factors and included shame, denial, fear, wanting to do it on their own, not feeling ready, and not wanting to seek care. Conclusions PWH experienced barriers largely at the individual level that prevented them from seeking alcohol treatment despite a recognized need, though many eventually sought care. Providers and public health professionals should consider helping to address various barriers, particularly internal barriers, when designing interventions to help PWH seek care.

Abstract While Alzheimer’s disease and other neurodegenerative diseases have traditionally been viewed as brain disorders, there is growing evidence indicating their manifestation in the eyes as well. The retina, being a developmental extension of the brain, represents the only part of the central nervous system that can be noninvasively imaged at a high spatial resolution. The discovery of the specific pathological hallmarks of Alzheimer’s disease in the retina of patients holds great promise for disease diagnosis and monitoring, particularly in the early stages where disease progression can potentially be slowed. Among various retinal imaging methods, hyperspectral imaging has garnered significant attention in this field. It offers a label-free approach to detect disease biomarkers, making it especially valuable for large-scale population screening efforts. In this review, we discuss recent advances in the field and outline the current bottlenecks and enabling technologies that could propel this field toward clinical translation.

Penile prosthesis surgery is a definitive treatment for erectile dysfunction (ED). The two categories of penile prosthesis are endorsed by professional guidelines, inflatable penile prosthesis (IPP) and malleable penile prosthesis (MPP). Each modality of penile prosthesis offers distinct advantages and incorporates specific design features, allowing for personalized device selection that aligns with individual needs and preferences. While the overall complication rate of penile implant surgery remains low, surgeons should maintain a high index of suspicion for complications in the perioperative time period. Multimodal analgesic regimens including nerve blocks and narcotic-free pathways should be administered to manage perioperative pain. Finally, the high patient satisfaction after penile prosthesis surgery underscores the success of this ED treatment option.

The latest advances in science, combined with the growing possibilities of modern technology, contributed to the improvement of fish feeding technology and fish farming in general. It is obvious that the expansion of the species composition of cultivated fish farming objects will continue, and the importance of feed and fish feeding technology will steadily increase. The developed recipes of starter feeds for juvenile fish and the technology of their production would make it possible to establish the production of these feeds for fish farms in Kazakhstan, as a result, the survival rate and growth rate of juvenile fish grown in industrial conditions would increase. The aim of the work was to develop recipes for starter feeds for pikeperch fry and technology for their production by extrusion, the development of these feeds to improve the efficiency of growing pikeperch in industrial conditions. According to the developed recipe, a starter feed for zander juveniles, balanced in terms of basic nutrients, was developed, a study was made of the effect of this feed on the efficiency and speed of growing zander juveniles. The dynamics of rearing juvenile pikeperch was studied when feeding the starter feed developed by the Kazakh Research Institute of Processing and Food Industry, with a feed coefficient of 1.28 and as a control foreign starter feed for trout “Aller Aqua” – 1.2. The materials of the article are of practical importance and the need for further research, they will help replenish the formulas of compound feed for the industrial cultivation of juvenile pike perch in fish farms of the Republic of Kazakhstan

Abstract Aliphatic diols such as ethylene and propylene glycol are the key products in the chemical industry for manufacturing polymers. The synthesis of these molecules usually implies sequential processes, including epoxidation of olefins using hydrogen peroxide or oxygen with subsequent hydrolysis to glycols. Direct hydroxylation of olefins by cheap and green oxidants is an economically attractive and environmentally friendly route for the synthesis of diols. Here, we report a photocatalytic reaction for the dihydroxylation of ethylene and propylene to their glycols at room temperature using water as the oxidant. The photocatalyst contains Pd clusters stabilized by sub-nanometric polyoxometalate with TiO2 as the host material. Under light irradiation, it results in production rates of ethylene glycol and propylene glycols of 146.8 mmol·gPd −1·h−1 and 28.6 mmol·gPd −1·h−1 with liquid-phase selectivities of 63.3 % and 80.0 %, respectively. Meanwhile, green hydrogen derived from water is produced as another valuable product. Combined spectroscopy investigation suggests that the reaction proceeds via π-bonded adsorption of olefins over Pd clusters with hydroxylation by hydroxyl radicals formed by photocatalytic dissociation of water.

Abstract Mucopolysaccharidoses are inherited metabolic disorders caused by the deficiency in lysosomal enzymes required to break down glycosaminoglycans. Accumulation of glycosaminoglycans leads to progressive, systemic degenerative disease. The central nervous system is particularly affected, resulting in developmental delays, neurological regression, and early mortality. Current treatments fail to adequately address neurological defects. Here we explore the potential of human induced pluripotent stem cell (hiPSC)-derived microglia progenitors as a one-time, allogeneic off-the-shelf cell therapy for several mucopolysaccharidoses (MPS). We show that hiPSC-derived microglia progenitors, possessing normal levels of lysosomal enzymes, can deliver functional enzymes into four subtypes of MPS knockout cell lines through mannose-6-phosphate receptor-mediated endocytosis in vitro. Additionally, our findings indicate that a single administration of hiPSC-derived microglia progenitors can reduce toxic glycosaminoglycan accumulation and prevent behavioral deficits in two different animal models of MPS. Durable efficacy is observed for eight months after transplantation. These results suggest a potential avenue for treating MPS with hiPSC-derived microglia progenitors.

Abstract Background The incidence of vitamin D deficiency among pregnant women remains high and is associated with vitamin D deficiency in infants. In normally breastfed infants, Bifidobacteriaceae and Lactobacillaceae are known to help in maintaining immunotolerance and prevent infection. Vitamin D in the gastrointestinal tract plays a role in determining the composition and function of intestinal bacteria. Preterm infants are vulnerable to intestinal dysbiosis and sepsis due to bacterial translocation. This study aimed to determine the association between vitamin D levels and intestinal dysbiosis. Methods It was a cohort study conducted in the Neonatal Unit, Cipto Mangunkusumo Hospital, Tertiary hospital in Indonesia, from November 2019 to January 2021. The inclusion criteria in this study were preterm infants with a gestational age of less than 32 weeks or a birth weight of less than 1500 g. Total 25-hydroxyvitamin D (25(OH)D) levels were collected from the umbilical cords of very preterm or very low birth weight infants. A fecal examination was performed on the seventh day of life to assess intestinal bacteria using real-time PCR for four bacterial genera: Bifidobacteriaceae, Lactobacillaceae, Enterobacteriaceae, and Clostridiaceae. Results A total of 43 infants were included in this study. Among the subjects, 53.4% had vitamin D deficiency. There was no association identified between vitamin D deficiency and intestinal dysbiosis (RR 0.67; 95% CI (0.15–2.82), p-value = 0.531). However, the ratio of Lactobacillacecae to Enterobacteriaceae was lower in those with vitamin D deficiency. Conclusion Vitamin D deficiency was not associated with dysbiosis in preterm infants. However, this study found that the ratio of Lactobacillaceae to Enterobacteriaceae in those with vitamin D deficiency was lower than in those without vitamin D deficiency. Further research is warranted to confirm this finding.

Abstract The characterization of genetic alterations in tumor samples has become standard practice for many human cancers to achieve more precise disease classification and guide the selection of targeted therapies. Cerebrospinal fluid (CSF) can serve as a source of tumor DNA in patients with central nervous system (CNS) cancer. We performed comprehensive profiling of CSF circulating tumor DNA (ctDNA) in 711 patients using an FDA-authorized platform (MSK-IMPACT™) in a hospital laboratory. We identified genetic alterations in 489/922 (53.0%) CSF samples with clinically documented CNS tumors. None of 85 CSF samples from patients without CNS tumors had detectable ctDNA. The distribution of clinically actionable somatic alterations was consistent with tumor-type specific alterations across the AACR GENIE cohort. Repeated CSF ctDNA examinations from the same patients identified clonal evolution and emergence of resistance mechanisms. ctDNA detection was associated with shortened overall survival following CSF collection. Next-generation sequencing of CSF, collected through a minimally invasive lumbar puncture in a routine hospital setting, provides clinically actionable cancer genotype information in a large fraction of patients with CNS tumors.

Abstract Background Fibroids are non-cancerous uterine growths that can cause symptoms impacting quality of life. The breadth of treatment options allows for patient-centered preference. While conversation aids are known to facilitate shared decision making, the implementation of these aids for uterine fibroids treatments is limited. We aimed to develop two end-user-acceptable uterine fibroids conversation aids for an implementation project. Our second aim was to outline the adaptations that were made to the conversation aids as implementation occurred. Methods We used a multi-phase user-centered participatory approach to develop a text-based and picture-enhanced conversation aid for uterine fibroids. We conducted a focus group with project stakeholders and user-testing interviews with eligible individuals with symptomatic uterine fibroids. We analyzed the results of the user-testing interviews using Morville’s Honeycomb framework. Spanish translations of the conversation aids occurred in parallel with the English iterations. We documented the continuous adaptations of the conversation aids that occurred during the project using an expanded framework for reporting adaptations and modifications to evidence-based interventions (FRAME). Results The first iteration of the conversation aids was developed in December 2018. Focus group participants (n = 6) appreciated the brevity of the tools and suggested changes to the bar graphs and illustrations used in the picture-enhanced version. User-testing with interview participants (n = 9) found that both conversation aids were satisfactory, with minor changes suggested. However, during implementation, significant changes were suggested by patients, other stakeholders, and participating clinicians when they reviewed the content. The most significant changes required the addition or deletion of information about treatment options as newer research was published or as novel interventions were introduced into clinical practice. Conclusions This multi-year project revealed the necessity of continuously adapting the uterine fibroids conversation aids so they remain acceptable in an implementation and sustainability context. Therefore, it is important to seek regular user feedback and plan for the need to undertake updates and revisions to conversation aids if they are going to be acceptable for clinical use.

Abstract Background Diabetes is associated with impairments in muscle mass and quality increasing the risk of sarcopenia. Thus, this study aimed to investigate the odds of sarcopenia and its associated risk factors among Qatari adults (> 18 years), while exploring the modulating effects of health and lifestyle factors. Methods Using a case–control design, data from 767 participants (481 cases with diabetes and 286 controls without diabetes) was collected from Qatar Biobank (QBB). Sociodemographic, lifestyle factors including dietary intake, anthropometric and biochemical measures were analyzed. Handgrip strength, Dual X-ray absorptiometry (DXA), and Bio-impedance were used to assess muscle strength, muscle mass and muscle quality, respectively. The risk of sarcopenia was estimated using the European consensus on definition and diagnosis of sarcopenia. Results Cases with diabetes were older (55 vs. 36 years; P

Abstract Background Sexually active adolescents sometimes seek contraceptives without parental consent, posing challenges due to minors' confidentiality and consent regulations. This is especially the case under the un-nuanced Israeli legal scheme regarding adolescents' care. Methods Israeli OBGYNs were contacted through mailing lists and social media groups and asked to fill an online questionnaire regarding their experience and protocols concerning prescription of contraceptives to minors. They were also asked about their comprehension of the relevant legal obligations, the importance they ascribe to different ethical interests and considerations, as well as their training. Results Of the 177 responding gynecologists, 132 (74.58%) consulted minors about contraceptives during the past year, regardless of a vast lack of training on providing care to minors. More than a third of respondents believed that there is no legal requirement to involve parents in the process, and only 8% assumed a legal obligation for parental involvement in all minors under the age of 18. Three quarters would "almost always" prescribe contraceptives without parental knowledge, if requested, while 20% never would. No correlation was found between respondents' practices and their perception of the relevant legal obligations. Participants agreed that the risk to the health of the minor as a result of having sex without contraceptives is of utmost importance. Yet, those willing to prescribe gave greater weight to this consideration, while those who do not prescribe were more concerned with the legal ramifications of such an act. The majority identified the age of 15 as the threshold for consistently prescribing contraceptives to minors without parental involvement. Conclusion This study highlights the significant gaps in both the legal framework and the training of Israeli OBGYNs, and further supports confidential prescription of contraceptives to minors 15 years and older, via Article 6 of the Israeli Legal Competence and Guardianship Law. Legislative reform, professional guidelines and education and training programs are all needed to ensure consistent and legally sound practices, that safeguard the health and rights of minors. It is imperative to guide healthcare providers, including OBGYNs prescribing contraceptives to minors, on managing the care of minors refusing parental involvement, clarifying the legal framework and ethical considerations involved.

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 Background Azithromycin has been shown to be beneficial in preventing infectious diseases, including malaria, infectious diarrhoea and pneumonia. A cluster randomised control trial on azithromycin MDA in children in Niger, Malawi and Tanzania found a reduction in all-cause under-five (U5) mortality in communities who received azithromycin compared to placebo. However, the reduction was largest and statistically significant only in Niger. The purpose of this trial is to evaluate the impact of azithromycin plus intermittent preventive treatment in infants (IPTi), recently renamed by the World Health Organisation as perennial malaria chemoprevention (PMC), with sulfadoxine-pyrimethamine (SP) on all-cause mortality up to 18 months of age in children living in areas of high mortality burden through the Expanded Program on Immunisation (EPI) in Sierra Leone. Methods The Improving Care through Azithromycin Research for Infants in Africa (ICARIA) trial is a phase III two-arm, individually randomised, double-blinded, placebo-controlled trial administering oral AZI (20 mg/kg bodyweight) at three time points to children attending EPI visits in Sierra Leone. A total of 20,560 infants attending the first EPI contact at around 6 weeks of age are recruited and randomised to AZI or placebo in a 1:1 ratio. The second and third AZI/placebo doses are given at 9 and 15 months of age. The primary outcome of the trial is all-cause mortality rate at 18 months of age assessed through mortality surveillance. Other trial outcomes include the impact on antimicrobial resistance, and on the immune response to certain key routine EPI immunisations, the safety of the intervention, the prevalence of SP resistance markers and the feasibility, and acceptability of adding AZI to the EPI programme. Discussion The trial will provide the evidence needed to inform policy regarding the adoption and large-scale implementation of AZI in areas of high-mortality burden in sub-Saharan Africa. Trial registration ClinicalTrials.gov NCT04235816. Registered on 22 January 2020. Pan-African Clinical Trials Registry PACTR202004540256535. Registered on 14 April 2020.

Abstract Background The impression section integrates key findings of a radiology report but can be subjective and variable. We sought to fine-tune and evaluate an open-source Large Language Model (LLM) in automatically generating impressions from the remainder of a radiology report across different imaging modalities and hospitals. Methods In this institutional review board-approved retrospective study, we collated a dataset of CT, US, and MRI radiology reports from the University of California San Francisco Medical Center (UCSFMC) (n = 372,716) and the Zuckerberg San Francisco General (ZSFG) Hospital and Trauma Center (n = 60,049), both under a single institution. The Recall-Oriented Understudy for Gisting Evaluation (ROUGE) score, an automatic natural language evaluation metric that measures word overlap, was used for automatic natural language evaluation. A reader study with five cardiothoracic radiologists was performed to more strictly evaluate the model’s performance on a specific modality (CT chest exams) with a radiologist subspecialist baseline. We stratified the results of the reader performance study based on the diagnosis category and the original impression length to gauge case complexity. Results The LLM achieved ROUGE-L scores of 46.51, 44.2, and 50.96 on UCSFMC and upon external validation, ROUGE-L scores of 40.74, 37.89, and 24.61 on ZSFG across the CT, US, and MRI modalities respectively, implying a substantial degree of overlap between the model-generated impressions and impressions written by the subspecialist attending radiologists, but with a degree of degradation upon external validation. In our reader study, the model-generated impressions achieved overall mean scores of 3.56/4, 3.92/4, 3.37/4, 18.29 s,12.32 words, and 84 while the original impression written by a subspecialist radiologist achieved overall mean scores of 3.75/4, 3.87/4, 3.54/4, 12.2 s, 5.74 words, and 89 for clinical accuracy, grammatical accuracy, stylistic quality, edit time, edit distance, and ROUGE-L score respectively. The LLM achieved the highest clinical accuracy ratings for acute/emergent findings and on shorter impressions. Conclusions An open-source fine-tuned LLM can generate impressions to a satisfactory level of clinical accuracy, grammatical accuracy, and stylistic quality. Our reader performance study demonstrates the potential of large language models in drafting radiology report impressions that can aid in streamlining radiologists’ workflows.

Abstract This single-arm phase II non-randomised trial (ACTRN12619001265167) evaluated trastuzumab emtansine in solid cancers with HER2 amplification or mutation detected by comprehensive genomic profiling. The primary objective was objective response (OR), while secondary objectives included the time to progression (TTP) on study to TTP on prior therapy ratio, progression-free survival (PFS) and overall survival (OS). The cohort included 16 tumours with HER2 mutations (group 1) and 16 with HER2 amplification (group 2). After 17 months median follow-up, ORs occurred in 19% of group 1 (1 salivary gland carcinoma (SGC), 2 lung cancers) and 25% of group 2 (3 SGCs, 1 uterine carcinoma). Fourteen of 29 TTP-evaluable patients achieved a TTP ratio ≥1.3, including 10 without an OR. Median PFS and OS were 4.5 (95% CI 2.1–7.0) and 18.2 months (95% CI 8.1-not reached) respectively. Trastuzumab emtansine showed modest ORs and a favourable change in disease trajectory in select HER2-altered solid cancers.

Abstract Glioblastoma remains one of the deadliest brain malignancies. First-line therapy consists of maximal surgical tumor resection, accompanied by chemotherapy and radiotherapy. Malignant cells escape surgical resection by migrating into the surrounding healthy brain tissue, where they give rise to the recurrent tumor. Based on gene expression, tumor cores can be subtyped into mesenchymal, proneural, and classical tumors, each being associated with differences in genetic alterations and cellular composition. In contrast, the adjacent brain parenchyma where infiltrating malignant cells escape surgical resection is less characterized in patients. Using spatial transcriptomics (n = 11), we show that malignant cells within proneural or mesenchymal tumor cores display spatially organized differences in gene expression, although such differences decrease within the infiltrated brain tissue. Malignant cells residing in infiltrated brain tissue have increased expression of genes related to neurodevelopmental pathways and glial cell differentiation. Our findings provide an updated view of the spatial landscape of glioblastomas and further our understanding of the malignant cells that infiltrate the healthy brain, providing new avenues for the targeted therapy of these cells after surgical resection.

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

Abstract Corn snakes are emerging models for animal colouration studies. Here, we focus on the Terrazzo morph, whose skin pattern is characterized by stripes rather than blotches. Using genome mapping, we discover a disruptive mutation in the coding region of the Premelanosome protein (PMEL) gene. Our transcriptomic analyses reveal that PMEL expression is significantly downregulated in Terrazzo embryonic tissues. We produce corn snake PMEL knockouts, which present a comparable colouration phenotype to Terrazzo and the subcellular structure of their melanosomes and xanthosomes is also similarly impacted. Our single-cell expression analyses of wild-type embryonic dorsal skin demonstrate that all chromatophore progenitors express PMEL at varying levels. Finally, we show that in wild-type embryos PMEL-expressing cells are initially uniformly spread before forming aggregates and eventually blotches, as seen in the adults. In Terrazzo embryos, the aggregates fail to form. Our results provide insights into the mechanisms governing colouration patterning in reptiles.

Abstract Background Unhealthy alcohol use represents a significant risk for morbidity and mortality among people living with HIV (PLWH), in part through its impact on HIV management. Chronic pain, a common comorbidity, exacerbates suboptimal engagement in the HIV care continuum and has reciprocal detrimental effects on alcohol outcomes. There are no integrated, accessible approaches that address these comorbid conditions among PLWH to date. This paper describes a research study protocol of an integrated telehealth intervention to reduce unhealthy drinking and chronic pain among PLWH (Motivational and Cognitive-Behavioral Management for Alcohol and Pain [INTV]). Methods Two-hundred and fifty PLWH with unhealthy drinking and chronic pain will be recruited nationally via online advertisement. Informed consent and baseline assessments occur remotely, followed by 15 days of ecological momentary assessment to assess alcohol use, chronic pain, functioning, and mechanisms of behavior change. Next, participants will be randomized to either the INTV or Control (CTL) condition. Individuals in both conditions will meet with a health counselor through videoconferencing following randomization, and those in the INTV condition will receive 6 additional sessions. At 3- and 6-months post-baseline, participants will complete outcome assessments. It is hypothesized that the INTV condition will result in reduced unhealthy alcohol use and pain ratings compared to the CTL condition. Conclusion This protocol paper describes a randomized controlled trial which tests the efficacy of a novel, integrated telehealth approach to reduce unhealthy alcohol use and chronic pain for PLWH, two common comorbid conditions that influence the HIV treatment cascade. ClinicalTrials.gov identifier NCT05503173.

Abstract Background Most people diagnosed with dementia live and die in community settings. This study aimed to: (i) describe the palliative care needs of patients with dementia at commencement of community palliative care; (ii) compare palliative care needs between patients with dementia and those with lung cancer and cardiovascular disease (CVD). Methods This is a population-based descriptive study that involved 8,727, 7,539 and 25,279 patients who accessed community palliative care across Australia principally because of dementia, CVD and lung cancer. Patients’ functional abilities, symptom burden and clinical condition were assessed at commencement of community alliative care using five validated instruments: Resource Utilisation Groups—Activities of Daily Living, Australia-modified Karnofsky Performance Status, Symptoms Assessment Scale, Palliative Care Problem Severity Score and Palliative Care Phase. We fitted ordinal logistic regression models to examine the differences in these assessments for dementia versus CVD and lung cancer, respectively. Results Overall, patients with dementia generally had low levels of distress from symptoms but poor functional problems. Compared to the other two diagnostic groups, palliative care for dementia was often initiated later and with shorter contacts. Also, patients with dementia presented with poorer functional performance (adjusted OR (aOR) = 4.02, Confidence Interval (CI): 3.68 – 4.38 for dementia vs CVD; aOR = 17.59, CI: 15.92 – 19.44 for dementia vs lung cancer) and dependency (aOR = 5.68, CI: 5.28 – 6.12 for dementia vs CVD; aOR = 24.97, CI: 22.77 – 27.39 for dementia vs lung cancer), but experienced lower levels of distress and problem severity for the majority of symptoms. Conclusion Community palliative care is often an ideal care option for many patients, particularly for those with dementia. We call for expansion of the palliative care workforce and options for home care support to optimize accessibility of community palliative care for dementia.

Este estudio presenta un modelo diseñado para predecir el rendimiento académico utilizando redes neuronales. Se enmarca en un enfoque cuantitativo y se categoriza como un estudio correlacional multivariado. La investigación se basa en una base de datos proveniente de una institución educativa, disponible en el repositorio de datos de la Universidad de California, Irvine. Se eligió R como el lenguaje de programación, con RStudio como entorno de desarrollo. Se adoptó la metodología CRISP-DM para llevar a cabo el análisis de datos. La construcción de la red neuronal se realizó utilizando el paquete nnet, disponible en el Comprehensive R Archive Network (CRAN). El modelo de red neuronal se aplicó a los datos recopilados de 649 estudiantes, y su capacidad predictiva se evaluó exhaustivamente. Tras compararlo con un modelo de regresión lineal múltiple, se observó que el modelo de red neuronal logró una efectividad del 87% en la predicción del rendimiento académico, evidenciando su idoneidad para este propósito.