bluuebunny/crossref_metadata_2025 huggingface dataset:
Obesity and its related factors among university medical students in Syria: A cross-sectional study
Authors: Naeem Ahmad , AlJaber Yazen , Kakaje Ameer , Ghareeb Amjad , Al Said Bayan
Published: August 2024

Introduction:

Obesity is a worldwide pandemic that has many contributing factors. There is very scarce data available on this issue for the population in Syria. We aim to evaluate the body mass index and related obesity rates of medical students as they are the role model for the general population. We aim to explore the breadth of potential associated factors including psychological, physical activity, dietary, and a broad array of lifestyle and socio-demographic factors.

Methods:

This is a cross-sectional study that was conducted at a major university in Damascus. Paper-based questionnaires were distributed that included the International Physical Activity Questionnaire short version and the Depression, Anxiety and Stress Scale.

Results:

The mean body mass index was 23.5 (±4.2) kg/m2 with 540 participants enrolled in this study. Males had significantly higher body mass index than females by 2.5 kg/m2 ( p < 0.001, χ2 = 47.9, V = 0.3). In our sample, 304 (60.68%) had normal body mass index (18.5–24.99), 40 (7.98%) were considered underweight (body mass index ⩽ 18.5), 120 (23.95%) were considered overweight (body mass index = 25–29.99) and 37 (7.39%) were considered obese. While many factors were found to be significantly associated with body mass index and obesity, only physical activity, depression, having a first-degree family history with obesity and poor dietary habits were associated in regression analyses evaluating all predictors concurrently.

Conclusion:

The findings reflect an ongoing epidemic of obesity. Our findings can guide targeted intervention for this young population who will become doctors and health role models in the future. More studies should be conducted to find the best possible ways to tackle this issue in the future.
A case of bilateral absent pulmonary arteries
Authors: Nishino Takako , Ando Makoto , Sakaguchi Genichi
Published: August 2024

Herein, we present the case of a 17-month-old boy with asplenia, bilaterally absent pulmonary arteries, and bilateral patent ductus arteriosus, who underwent a successful Fontan operation. The central pulmonary artery was created using a pericardial roll, which was initially oversized due to the elevated pressure from the systemic-to-pulmonary shunt. The size of the roll was reduced through the process of pressure reduction by bidirectional Glenn and Fontan operations. This case provides an example of blood source-associated size transition of the pericardial roll used in the pulmonary position. Recognizing this phenomenon is vital for the successful management of this patient group.
Unearthing slow violence in the Anthropocene: A study of myth and ethics in Amitav Ghosh’s Jungle Nama
Authors: Bera Priyanka
Published: August 2024

The planetary crisis, emerging out of the Anthropocene, significantly contributes to a continuous tension between human needs and desire; and Nature’s capacity to accommodate those by subsidizing the fundamental balance between human and non-human welfare. These long-term invisible phenomena of extreme anthropocentric metamorphoses not only endanger the culture and ethnicity of the indigenous community but also entail invisible and incomprehensible constant suffering in the form of ‘slow violence’. Ghosh’s first-ever book in verse, Jungle Nama, renders two parallel narratives simultaneously – a tale of colonial oppression on the eco-people through the slow aftermath of climatic violence and the establishment of ecojustice through the allegorical rendering of the largest deltaic mangrove forest, the Sundarbans’ mythical tale of Bon Bibi. Given this account, on the one hand, the aim of this paper is to explore the interplay between myth and ecoethics that interconnects human and other-than-human lives in Nature equilibrating human greed and need, with particular reference to the mythical tale of Bon Bibi legend. On the other hand, in contextualizing the complex phenomenon of Rob Nixon’s ‘slow violence’, where the indigenous people are completely unaware of the fact that they are living through the slow aftermath of climatic violence, the paper, therefore, seeks to highlight the multiplication of existential threats to the sense of belongingness, traditional cultural practices, the ethnicity, and identity of the Sundarbans’ indigenous people due to the flawed notion of settler colonialism.
From attention economy to cognitive lock-ins
Authors: Hansen Morten
Published: August 2024

The economic logic of the attention economy is frequently used to critique and respond to the dangers of unfettered technological expansion, including nascent platforms and products powered by generative artificial intelligence. This commentary warns that while large parts of the internet have been financed through such business models, there is no guarantee that emerging generative artificial intelligence products will be commercialized in this way too. Instead, I argue, we must look beyond the attention economy to predict the future of monetization of an industry already mired in anti-competitive practices. Using popular large language models such as OpenAI’s ChatGPT as a case, I discuss how some platforms are developing computational dependencies between technology and their users. I propose the term ‘cognitive lock-in’ to help us unpack the implications of such technological dependencies, and redirect the study of this nascent business model.
Evaluation of the gamified application KIJANI to promote physical activity in children and adolescents: A multimethod study
Authors: Willinger Laura , Schweizer Florian , Böhm Birgit , Scheller Daniel A , Jonas Stephan , Oberhoffer-Fritz Renate , Müller Jan , Reimer Lara Marie
Published: August 2024

Objective

Digital approaches have the potential to make activity promotion attractive and age-appropriate for children and adolescents. KIJANI is a mobile application aiming to increase physical activity (PA) in youth via gamification and augmented reality. This study investigates the user experience with KIJANI through a multimethod approach.

Approaches

KIJANI is based on the concept that virtual coins can be earned through PA, for example, in the form of collected step counts. With these coins, blocks can be bought, which can be used to create virtual buildings and landscapes and integrate these into the player's real-world environment via augmented reality. To evaluate the user experience, participants played KIJANI in groups of three for 25 min. Afterwards KIJANI was evaluated qualitatively with one-on-one semi-structured interviews as well as quantitatively with standardized questionnaires.

Results

Overall, 22 participants (12.6 ± 1.7 years, 6 girls) were included in the study. The overall game concept and realization were well received by the target group. Study participants did have various and creative ideas for the further development of KIJANI. The majority ( n = 16) thought that using KIJANI would increase their PA level. User experience based on the UEQ scale was (mean ± SD): attractiveness (1.78 ± 1.82), perspicuity (2.15 ± 0.680), efficiency (0.67 ± 1.25), dependability, (1.21 ± 0.93), stimulation (1.24 ± 1.78), and novelty (1.27 ± 1.34).

Conclusion

With these insights, a further step has been taken in the participatory development of KIJANI. Apps like KIJANI appear to be suitable for PA promotion in children and adolescents.
The reinvention of “locality”: Imagining the local society with local media
Authors: Wang Wei , Guan Huixin
Published: August 2024

In this essay, we draw on the history of internet-based local media at the county level in China to investigate the social implications of the internet for the local society. We take a “formative” approach and analyze the social processes of the reinvention of “locality” from the spatial, economic, and political aspects. We view “locality” not only as the assemblage of different places but also as a theoretical scaffolding that can stimulate a refreshed imagination of geography and media. The scales are reinvented, or redefined, by the digital fabrics of these social platforms which align geographical scales for content producers, including grassroots and official stakeholders. “Locality” is reimagined with internet-based local media. By discussing what is considered as “locality” in the spatial, economic, and political senses from a social perspective, we have explored the mutual shaping of internet-based media practices and the physical world. The social implications of the internet manifest themselves profoundly in the reinvention of “locality.”
No Differences in Major In-Hospital Outcome Metrics When Comparing the Direct Lateral Approach to the Posterior Approach for Hemiarthroplasties After Traumatic Displaced Femoral Neck Fractures
Authors: Morgan Steven , Jarvis Stephanie , Conti Alexander , Staudinger Kelsey , Reynolds Cassandra , Greenseid Samantha , Bar-Or David
Published: August 2024

Introduction

The surgical approach of hemiarthroplasty for displaced femoral neck fractures remains debated. The study objective was to compare in-hospital outcomes for geriatric displaced femoral neck fractures treated with hemiarthroplasty based on surgical approach (direct lateral vs. posterior approach).

Materials and Methods

This retrospective cohort study included geriatric patients (≥60 y/o) admitted 7/1/2016-3/31/2020 treated with hemiarthroplasty. Outcomes included: operative time (incision to closure), length of stay (HLOS), and blood loss volume (mL). The Harding direct lateral approach was compared to the posterior approach; P < .05.

Results

There were 164 patients (59% direct lateral, 41% posterior). Patients treated with the direct lateral approach had an advanced directive ( P = .03), dementia, ( P = .03), or were functionally dependent ( P = .03) more often than patients treated with the posterior approach. Time to surgery was comparable between groups ( P = .52). The direct lateral approach was associated with a shorter operative time (2.3 vs. 2.8 h, P = .03), a longer HLOS (5.0 vs. 4.0 days, P < .01), and a lower median volume of blood loss (50 vs. 100 mL, P = .01), than the posterior approach, respectively. In a stratified analysis, for those who were not functionally dependent, did not have dementia or an advanced directive, the direct lateral approach led to a longer HLOS ( P = .03) and shorter operative time ( P = .04) than the posterior approach. Whereas among those who were functionally dependent, had dementia or had an advanced directive, the direct lateral approach led to less blood loss ( P = .02) than the posterior approach.

Discussion

While those treated with the direct lateral approach lost significantly less blood, they had a significantly longer HLOS than those treated with the posterior approach. Comorbidities significantly modified outcomes, which may suggest their presence could assist with treatment decisions.

Conclusions

This study found neither approach, the direct lateral nor posterior, to be superior. Surgical approach could remain physician preference.
From Risk to Resilience? Hazardous Drinking Trajectories in and Beyond the Last Years of University Life
Authors: Rubio Milagros , Cillessen Antonius H. N. , Luijten Maartje , Vink Jacqueline M. , Verhagen Maaike
Published: August 2024

In this study, we examined the effects of loneliness, social support, and stress resilience on alcohol consumption and problems among university students in their final years of education during the COVID-19 pandemic. We surveyed 437 students with a pre-pandemic history of heavy episodic drinking across five waves from February 2021 to May 2023. Our findings showed that stress resilience significantly reduced alcohol-related problems over time. Those who frequently drank before the pandemic experienced a slower decline in problems, suggesting a delay in maturing out. Men reported higher hazardous drinking, yet gender did not influence trajectories. Loneliness initially correlated with increased drinking problems, without long-term effects, and social support had no significant impact. Our results highlight that stress resilience is essential for preventing alcohol problems, reveal the persistence of hazardous drinking into later university years, and suggest that the COVID-19 pandemic shifted typical drinking patterns in the Netherlands, marked by significant post-lockdown rebounds.
HIV Self-Testing for Efficient PrEP Delivery Is Highly Acceptable and Feasible in Public Health HIV Clinics in Kenya: A Mixed Methods Study
Authors: Ogello Vallery , Ngure Kenneth , Mwangi Paul , Owidi Emmah , Wairimu Njeri , Etyang Lydia , Mwangi Margaret , Mwangi Dominic , Maina Simon , Mugo Nelly , Mugwanya Kenneth
Published: August 2024

HIV self-testing (HIVST) has the potential to reduce barriers associated with clinic-based preexposure prophylaxis (PrEP) delivery. We conducted a substudy nested in a prospective, pilot implementation study evaluating patient-centered differentiated care services. Clients chose either a blood-based or oral fluid HIVST kit at the first refill visit. Data were abstracted from program files and surveys were administered to clients. We purposively sampled a subset of PrEP clients and their providers to participate in in-depth interviews. We surveyed ( n = 285). A majority (269/285, 94%) reported HIV risk. Blood-based HIVST was perceived as easy to use (76/140, 54%), and (41/140, 29%) perceived it to be more accurate. Oral fluid-based HIVST was perceived to be easy to use (95/107, 89%), but almost all (106/107, 99%) perceived it as less accurate. HIVST improved privacy, reduced workload, and saved time. HIVST demonstrates the potential to streamline facility-based PrEP care in busy African public health facilities.
Ensemble Algorithm for Risk Prediction of Clinical Failure After Anterior Cruciate Ligament Reconstruction
Authors: Zhang Tianlun , Ye Zipeng , Cai Jiangyu , Chen Jiebo , Zheng Ting , Xu Junjie , Zhao Jinzhong
Published: August 2024

Background:

Patient-specific risk profiles of clinical failure after anterior cruciate ligament reconstruction (ACLR) are meaningful for preoperative surgical planning and postoperative rehabilitation guidance.

Purpose:

To create an ensemble algorithm machine learning (ML) model and ML-based web-based tool that can predict the patient-specific risk of clinical failure after ACLR.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

Included were 432 patients (mean age, 26.8 ± 8.4 years; 74.1% male) who underwent anatomic double-bundle ACLR with hamstring tendon autograft between January 2010 and February 2019. The primary outcome was the probability of clinical failure at a minimum 2-year follow-up. The authors included 24 independent variables for feature selection and model development. The data set was split randomly into training sets (75%) and test sets (25%). Models were built using 4 ML algorithms: extreme gradient boosting, random forest, light gradient boosting machine, and adaptive boosting. In addition, a weighted-average voting (WAV) ensemble model was constructed using the ensemble-voting technique to predict clinical failure after ACLR. Concordance (area under the receiver operating characteristic curve [AUC]), calibration, and decision curve analysis were used to evaluate predictive performances of the 5 models.

Results:

Clinical failure occurred in 73 of the 432 patients (16.9%). The 8 most important predictors for clinical failure were follow-up period, high-grade preoperative knee laxity, time from injury to ACLR, participation in competitive sports, posterior tibial slope, graft diameter, age at surgery, and medial meniscus resection. The WAV ensemble algorithm achieved the best predictive performance based on concordance (AUC, 0.9139), calibration (calibration intercept, –0.1806; calibration slope, 1.2794; Brier score, 0.0888), and decision curve analysis (greatest net benefits) and was used to develop an web-based application to predict a patient's clinical failure risk of ACLR.

Conclusion:

The WAV ensemble algorithm was able to accurately predict patient-specific risk of clinical failure after ACLR. Clinicians and patients can use the web-based application during preoperative consultation to understand individual prediction outcomes.
Prognostic Factors on Preoperative MRI for Patient-Reported Outcomes After Posterior Medial Meniscus Root Repair
Authors: Flores Sergio E. , Manatrakul Rawee , Anigwe Christopher , Ngarmsrikam Chotigar , Feeley Brian T. , Ma C. Benjamin , Link Thomas M. , Lansdown Drew A.
Published: August 2024

Background:

Repair of posterior medial meniscus root (PMMR) tears has demonstrated favorable outcomes and may prevent rapid progression of knee osteoarthritis; however, there is a paucity of data regarding prognostic factors affecting postoperative outcomes.

Purpose/Hypothesis:

The purpose of this study was to identify factors on preoperative magnetic resonance imaging (MRI) that predict postoperative outcomes after PMMR repair. It was hypothesized that patients with increasing levels of degenerative changes as evaluated through semiquantitative preoperative MRI scans would have worse postoperative patient-reported outcome (PRO) scores.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

Patients who underwent PMMR repair between 2012 and 2020 and had minimum 2-year follow-up data were enrolled. Pre- and postoperative visual analog scale pain scores and postoperative PRO surveys including the Patient-Reported Outcomes Measurement Information System–Physical Function, Lysholm knee score, and Knee injury and Osteoarthritis Outcome Score (KOOS) were collected. Patients who achieved the Patient Acceptable Symptom State (PASS) on the KOOS subscales were reported. Two fellowship-trained musculoskeletal radiologists reviewed preoperative MRIs and calculated the Whole-Organ Magnetic Resonance Imaging Score for meniscus, cartilage, bone marrow edema–like lesions (BMELL), and meniscal extrusion. Statistical analysis was performed using the 2-sample t test, Mann-Whitney test, and Fisher exact test for categorical variables.

Results:

A total of 29 knees in 29 patients were evaluated (22 female, 7 male; mean age at surgery, 52.3 ± 9.9 years; body mass index, 27.6 ± 5.6 kg/m2; mean follow-up, 59.6 ± 26.5 months). Visual analog scale for pain scores decreased significantly from preoperatively (4.9 ± 2.0) to final follow-up (1.6 ± 1.9) ( P < .001), and the percentage of patients meeting the PASS ranged from 44.8% for KOOS Sport and Recreation to 72.4% for KOOS Pain and KOOS Quality of Life. Patients with medial tibial BMELL (MT-BMELL) had significantly lower KOOS Symptoms scores (76.1 ± 17.3 vs 88.4 ± 9.7 without MT-BMELL; P = .032). Cartilage quality and presence of meniscal extrusion were not associated with outcomes.

Conclusion:

Patients with MT-BMELL on their preoperative MRI in the setting of PMMR tear were found to have worse KOOS Symptoms scores after PMMR repair.
Influence of eHealth Literacy and Health Promotion Behavior on Body Mass Index of Workers in the Public Sector
Authors: Bello Cecilia Bukola , Balogun Mary Omolara , Ogundipe Laofe , Olubiyi Simeon Kayode , Bamigboye Theresa Olaitan , Esan Deborah Tolulope
Published: August 2024

Background

Adequate eHealth literacy and health promotion behavior (HPB) are important to achieve good health-related quality of life. There is limited information on the influence of eHealth literacy and HPB on body mass index (BMI) in our setting and among public service workers.

Objectives

This study assessed the eHealth literacy, HPB, and BMI of public service workers and determined the influence of eHealth literacy and HPB on BMI.

Design

A descriptive cross-sectional design was adopted.

Methods

A simple random sampling technique was used to select 440 public service workers from civil service of redacted. A structured questionnaire was used to collect data on socio-demographics, eHealth literacy, and HPB. Weight and height were measured and BMI was calculated. Data were analyzed using frequency, percentage, mean, standard deviation, and logistic regression analysis. The significant level was set at 0.05.

Results

More than one quarter (28.2%) of respondents had low eHealth literacy, and more than one third (42.5%) had inadequate (30.0% fair and 12.5% poor) HPB. An average (50.5%) had a level of obesity that ranged from preobesity to type 2 obesity. There was a significant association between eHealth literacy and HPB with the BMI of respondents at p < .05.

Conclusion

There was inadequate eHealth literacy and HPB among public service workers. An average of the workers had a level of obesity that ranged from pre-obesity to type 2 obesity. There was a significant association between eHealth literacy and BMI and also between HPB and BMI of respondents. Community health professionals should assist public service workers to develop competencies and skills useful in evaluating health information on the Internet and applying such information to make informed decisions.
Customized Mobile App for Residents Rotating Through Pediatric Critical Care Unit
Authors: Tseng Yu Shan , Thomas Ronald , Sarnaik Ajit
Published: August 2024

Objective

Physicians often use mobile apps for patient care, but few apps are dedicated to pediatric critical care medicine (PCCM). This study developed a mobile app specifically for Pediatric Critical Care Unit (PICU) residents to aid their onboarding process and aimed to assess whether it could enhance their confidence and comfort levels.

Method

From March 2020 to April 2021, 90 residents participated and completed pre- and post-rotation quizzes with 20 questions each. Quiz score differences between the control and app groups were analyzed using t-tests. A survey was also administered at the end of the rotation to compare comfort level and confidence in PCCM knowledge pre- and post-rotation.

Results

Enrollment included 50 residents in the control group and 40 in the app group. The participation rate was 100%, but not all participants completed both quizzes and survey. The app group showed a significantly greater improvement in quiz scores from pre- to post-rotation compared to the control group (increase of 0.23 questions vs 1.67, p = 0.045). However, the two groups had no significant differences in confidence in PCCM knowledge (p = 0.246) or comfort levels (p = 0.776) in the PICU.

Conclusions

This study found no significant difference in confidence levels between the App and control groups at the end of the PICU rotation. However, the App group outperformed the control group in knowledge assessments. Frequent use of the app likely reinforced essential concepts and facilitated adaptation to the PICU service. Overall, the app's positive impact on knowledge and adaptation indicates it is a valuable tool for enhancing medical residents’ educational experiences in busy clinical environments.
Planning with Purpose and Intent: Designing Lesson Objectives and Assessments to Embed Social Emotional Learning in Elementary General Music
Authors: Lloyd Melissa A.
Published: August 2024

Social Emotional Learning (SEL) is a topic of growing interest and relevance to music educators, particularly those who teach elementary general music. While there are natural connections between music education and SEL, the incorporation of SEL into a music curriculum must be done with purpose and intent. Many elementary general music teachers struggle with purposefully embedding SEL into their existing curricula, due to factors such as a lack of time, relevance, and inadequate preparation. In this article, elementary general music teachers will discover ways to design lesson objectives and assessments that purposely embed SEL skills with musical outcomes to support the social, emotional, and musical development of all students in their classroom.
Case report: response to immunotherapy and association with the fh gene in hereditary leiomyomatosis and renal cell cancer-associated renal cell cancer
Authors: Gao Fangfang , Gu Dejian , Zhang He , Shi Chao , Du Feng , Zheng Bo , Wu Huijuan , Zhao Yanqiu
Published: August 2024

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant syndrome caused by a germline mutation in the fumarate hydratase (FH) gene that manifests with cutaneous leiomyomas, uterine fibroids, and renal cell cancer (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have aggressive clinical courses, but there is no standardized therapy for advanced HLRCC-RCC. In this study, we described a case of aggressive HLRCC in a 33-year-old female who exhibited a novel heterozygous germline insertion mutation in exon 8 of the FH gene (c.1126 C > T; p.Q376*). The patient underwent laparoscopic resection of the right kidney, but metastases appeared within 3 months after surgery. Histological staining of the resected tumor revealed high expression levels of programmed cell death-ligand 1 (PD-L1). Therefore, the patient was treated with immunotherapy. The patient achieved a partial response to immunotherapy, and the treatment of metastatic lesions has continued to improve. A thorough literature review pinpointed 76 historical cases of HLRCC-RCC that had undergone immunotherapy. From this pool, 46 patients were selected for this study to scrutinize the association between mutations in the FH gene and the effectiveness of immunotherapy. Our results indicate that immunotherapy could significantly improve the overall survival (OS) of patients with HLRCC-RCC. However, no influence of different mutations in the FH germline gene on the therapeutic efficacy of immunotherapy was observed. Therefore, our study suggested that immunotherapy was an effective therapeutic option for patients with HLRCC regardless of the type of FH germline mutation.
Challenges in institutionalizing evidence-informed priority setting for health service packages: a qualitative document and interview analysis from Iran
Authors: Sajadi Haniye Sadat , Safikhani Hamidreza , Olyaeemanesh Alireza , Majdzadeh Reza
Published: August 2024

Background

Setting and implementing evidence-informed health service packages (HSPs) is crucial for improving health and demonstrating the effective use of evidence in real-world settings. Despite extensive training for large groups on evidence generation and utilization and establishing structures such as evidence-generation entities in many countries, the institutionalization of setting and implementing evidence-informed HSPs remains unachieved. This study aims to review the actions taken to set the HSP in Iran and to identify the challenges of institutionalizing the evidence-informed priority-setting process.

Methods

Relevant documents were obtained through website search, Google queries, expert consultations and library manual search. Subsequently, we conducted nine qualitative semi-structured interviews with stakeholders. The participants were purposively sampled to represent diverse backgrounds relevant to health policymaking and financing. These interviews were meticulously audio-recorded, transcribed and reviewed. We employed the framework analysis approach, guided by the Kuchenmüller et al. framework, to interpret data.

Results

Efforts to incorporate evidence-informed process in setting HSP in Iran began in the 1970s in the pilot project of primary health care. These initiatives continued through the Health Transformation Plan in 2015 and targeted disease-specific efforts in 2019 in recent years. However, full institutionalization remains a challenge. The principal challenges encompass legal gaps, methodological diversity, fragile partnerships, leadership changeovers, inadequate financial backing of HSP and the dearth of an accountability culture. These factors impede the seamless integration and enduring sustainability of evidence-informed practices, hindering collaborative decision-making and optimal resource allocation.

Conclusions

Technical aspects of using evidence for policymaking alone will not ensure sustainability unless it achieves the necessary requirements for institutionalization. While addressing all challenges is crucial, the primary focus should be on required transparency and accountability, public participation with an intersectionality lens and making this process resilience to shocks. It is imperative to establish a robust legal framework and a strong and sustainable political commitment to embrace and drive change, ensuring sustainable progress.
Protocol for a type 3 hybrid implementation cluster randomized clinical trial to evaluate the effect of patient and clinician nudges to advance the use of genomic medicine across a diverse health system
Authors: Raper Anna C. , Weathers Benita L. , Drivas Theodore G. , Ellis Colin A. , Kripke Colleen Morse , Oyer Randall A. , Owens Anjali T. , Verma Anurag , Wileyto Paul E. , Wollack Colin C. , Zhou Wenting , Ritchie Marylyn D. , Schnoll Robert A. , Nathanson Katherine L.
Published: August 2024

Background

Germline genetic testing is recommended for an increasing number of conditions with underlying genetic etiologies, the results of which impact medical management. However, genetic testing is underutilized in clinics due to system, clinician, and patient level barriers. Behavioral economics provides a framework to create implementation strategies, such as nudges, to address these multi-level barriers and increase the uptake of genetic testing for conditions where the results impact medical management.

Methods

Patients meeting eligibility for germline genetic testing for a group of conditions will be identified using electronic phenotyping algorithms. A pragmatic, type 3 hybrid cluster randomization study will test nudges to patients and/or clinicians, or neither. Clinicians who receive nudges will be prompted to either refer their patient to genetics or order genetic testing themselves. We will use rapid cycle approaches informed by clinician and patient experiences, health equity, and behavioral economics to optimize these nudges before trial initiation. The primary implementation outcome is uptake of germline genetic testing for the pre-selected health conditions. Patient data collected through the electronic health record (e.g. demographics, geocoded address) will be examined as moderators of the effect of nudges.

Discussion

This study will be one of the first randomized trials to examine the effects of patient- and clinician-directed nudges informed by behavioral economics on uptake of genetic testing. The pragmatic design will facilitate a large and diverse patient sample, allow for the assessment of genetic testing uptake, and provide comparison of the effect of different nudge combinations. This trial also involves optimization of patient identification, test selection, ordering, and result reporting in an electronic health record-based infrastructure to further address clinician-level barriers to utilizing genomic medicine. The findings may help determine the impact of low-cost, sustainable implementation strategies that can be integrated into health care systems to improve the use of genomic medicine.

Trial registration

ClinicalTrials.gov. NCT06377033. Registered on March 31, 2024. https://clinicaltrials.gov/study/NCT06377033?term=NCT06377033&rank=1
Buyang Huanwu decoction ameliorates myocardial injury and attenuates platelet activation by regulating the PI3 kinase/Rap1/integrin α(IIb)β(3) pathway
Authors: Gao Jiaming , Guo Hao , Li Junmei , Zhan Min , You Yue , Xin Gaojie , Liu Zixin , Fan Xiaodi , Gao Qinghe , Liu Jianxun , Zhang Yehao , Fu Jianhua
Published: August 2024

Background

Buyang Huanwu Decoction (BYHWD) is a traditional Chinese medicine to treat the syndrome of qi deficiency and blood stasis. Platelets play an important role in regulating thrombus and inflammation after ischemic injury, studies have shown that BYHWD regulate myocardial fibrosis and exert anti-inflammatory effects through IL-17 and TLR4 pathways, but the mechanism of platelet activation by BYHWD in stable coronary heart disease is still unknown. In the present study, model of left anterior descending coronary artery ligation was applied to investigate the mechanisms of BYHWD on modulating platelets hyperreactivity and heart function after fibrosis of ischemic myocardial infarction (MI).

Methods

Myocardial infarction model was constructed by ligation of the left anterior descending coronary artery. The rats were randomly divided into five groups: sham, model, MI with aspirin (positive), MI with a low dosage of BYHWD (BYHWD-ld) and MI with a high dosage of BYHWD (BYHWD-hd) for 28 days.

Results

Coronary artery ligation prominently induced left ventricle dysfunction, increased cardiomyocyte fibrosis, which was accompanied by platelets with hyperreactivity, and high levels of inflammatory factors. BYHWD obviously reversed cardiac dysfunction and fibrosis, increased the thickness of the left ventricular wall, and inhibited aggregation ratio and CD62p expression. BYHWD restored the mitochondrial respiration of platelets after MI, concomitant with an increased telomere expression and decreased inflammation. According to the result of transcriptome sequencing, we found that 106 differentially expressed genes compared model with BYHWD treatment. Enrichment analysis screened out the Ras-related protein Rap-1 (Rap1) signaling pathway and platelet activation biological function. Quantitative real-time PCR and Western blotting were applied to found that BYHWD reduced the expression of Rap1/PI3K-Akt/Src-CDC42 genes and attenuated the overactivity of PI3 kinase/Rap1/integrin α(IIb)β(3) pathway.

Conclusion

BYHWD reduced inflammation and platelet activation via the PI3 kinase/Rap1/integrin α(IIb)β(3) pathway and improved heart function after MI.

Graphical Abstract
Artemisinin ameliorates thyroid function and complications in adult male hypothyroid rats via upregulation of the L1 cell adhesion molecule
Authors: Li Lingling , Xu Haifan , Hu Zecheng , Li Li
Published: August 2024

Background

Hypothyroidism, a common worldwide syndrome caused by insufficient thyroid hormone secretion, affects number of people at different ages. Artemisinin (ART), a well-known effective agent in the treatment of malaria, also has anti-oxidative stress functions in various diseases. The L1 cell adhesion molecule exerts multiple protective roles in diseased systems. The aim of the present study was to evaluate the role of ART in adult male hypothyroid rats and the underlying mechanisms.

Methods

The propylthiouracil (PTU) rat model was treated with or without 5 mg/kg ART and with or without L1 short-interfering RNA (siRNA), followed by the experiments to determine the effect of ART on thyroid function, depression and anxiety, cognition impairments, liver, kidney and heart functions, and oxidative stress.

Results

In the current study, it was shown that ART can ameliorate thyroid function, mitigate depression and anxiety symptoms, attenuate cognition impairments, improve liver, kidney and heart functions, and inhibit oxidative stress; however, the effects exerted by ART could not be observed when L1 was silenced by L1 siRNA.

Conclusion

These results indicated that ART can upregulate the L1 cell adhesion molecule to ameliorate thyroid function and the complications in adult male hypothyroid rats, laying the foundation for ART to be a novel strategy for the treatment of hypothyroidism.
Genomic characterization of AML with aberrations of chromosome 7: a multinational cohort of 519 patients
Authors: Halik Adriane , Tilgner Marlon , Silva Patricia , Estrada Natalia , Altwasser Robert , Jahn Ekaterina , Heuser Michael , Hou Hsin-An , Pratcorona Marta , Hills Robert K. , Metzeler Klaus H. , Fenwarth Laurene , Dolnik Anna , Terre Christine , Kopp Klara , Blau Olga , Szyska Martin , Christen Friederike , Krönke Jan , Vasseur Loïc , Löwenberg Bob , Esteve Jordi , Valk Peter J. M. , Duchmann Matthieu , Chou Wen-Chien , Linch David C. , Döhner Hartmut , Gale Rosemary E. , Döhner Konstanze , Bullinger Lars , Yoshida Kenichi , Damm Frederik
Published: August 2024

Background

Deletions and partial losses of chromosome 7 (chr7) are frequent in acute myeloid leukemia (AML) and are linked to dismal outcome. However, the genomic landscape and prognostic impact of concomitant genetic aberrations remain incompletely understood.

Methods

To discover genetic lesions in adult AML patients with aberrations of chromosome 7 [abn(7)], 60 paired diagnostic/remission samples were investigated by whole-exome sequencing in the exploration cohort. Subsequently, a gene panel including 66 genes and a SNP backbone for copy-number variation detection was designed and applied to the remaining samples of the validation cohort. In total, 519 patients were investigated, of which 415 received intensive induction treatment, typically containing a combination of cytarabine and anthracyclines.

Results

In the exploration cohort, the most frequently mutated gene was TP53 (33%), followed by epigenetic regulators (DNMT3A, KMT2C, IDH2) and signaling genes (NRAS, PTPN11). Thirty percent of 519 patients harbored ≥ 1 mutation in genes located in commonly deleted regions of chr7—most frequently affecting KMT2C (16%) and EZH2 (10%). KMT2C mutations were often subclonal and enriched in patients with del(7q), de novo or core-binding factor AML (45%). Cancer cell fraction analysis and reconstruction of mutation acquisition identified TP53 mutations as mainly disease-initiating events, while del(7q) or −7 appeared as subclonal events in one-third of cases. Multivariable analysis identified five genetic lesions with significant prognostic impact in intensively treated AML patients with abn(7). Mutations in TP53 and PTPN11 (11%) showed the strongest association with worse overall survival (OS, TP53: hazard ratio [HR], 2.53 [95% CI 1.66–3.86]; P < 0.001; PTPN11: HR, 2.24 [95% CI 1.56–3.22]; P < 0.001) and relapse-free survival (RFS, TP53: HR, 2.3 [95% CI 1.25–4.26]; P = 0.008; PTPN11: HR, 2.32 [95% CI 1.33–4.04]; P = 0.003). By contrast, IDH2-mutated patients (9%) displayed prolonged OS (HR, 0.51 [95% CI 0.30–0.88]; P = 0.0015) and durable responses (RFS: HR, 0.5 [95% CI 0.26–0.96]; P = 0.036).

Conclusion

This work unraveled formerly underestimated genetic lesions and provides a comprehensive overview of the spectrum of recurrent gene mutations and their clinical relevance in AML with abn(7). KMT2C mutations are among the most frequent gene mutations in this heterogeneous AML subgroup and warrant further functional investigation.
Ac-HSP20 regulates autophagy and promotes the encystation of Acanthamoeba castellanii by inhibiting the PI3K/AKT/mTOR signaling pathway
Authors: Guo Siyao , Liu Di , Wan Xi , Guo Dingrui , Zheng Meiyu , Zheng Wenyu , Feng Xianmin
Published: August 2024

Background

The encystation of Acanthamoeba castellanii has important ecological and medical significance. Blocking encystation is the key to preventing transmission and curing infections caused by A. castellanii. The formation of autophagosomes is one of the most important changes that occur during the encystation of Acanthamoeba. Our previous studies have shown that the heat shock protein 20 of A. castellanii (Ac-HSP20) is involved in its encystation. This study aimed to determine the role and mechanism of Ac-HSP20 in regulating autophagy involved in the encystation of A. castellanii.

Methods

Immunofluorescence assay, western blotting and transmission electron microscopy were used to analyze the dynamic changes in autophagy during the initiation and continuation of encystation. The knockdown of Ac-HSP20 was performed to clarify its regulation of encystation and autophagy and to elucidate the molecular mechanism by which Ac-HSP20 participates in autophagy to promote cyst maturation.

Results

The encystation rates and autophagosomes were significantly decreased by treatment with the autophagy inhibitor 3-MA. The autophagy marker LC3B and autophagic lysosomes increased with the induced duration of encystation and reached the maximum at 48 h. The encystation rate, LC3B expression and autophagosomes decreased when Ac-HSP20 was knocked down by siRNA transfection. In addition, the expression levels of Ac-HSP20 and LC3B increased and the expressions of p-AKT and p-mTOR decreased after 48 h of encystation without knockdown. However, the expressions of p-AKT and p-mTOR increased while the expression of LC3B decreased under the knockdown of Ac-HSP20. Furthermore, the protein expression of LC3B increased when the PI3K/AKT/mTOR signaling pathway was inhibited but decreased when the pathway was activated.

Conclusions

The results demonstrated that autophagy is positively correlated with the encystation of A. castellanii, and Ac-HSP20 regulates autophagy to maintain the homeostasis of A. castellanii by inhibiting the PI3K /AKT /mTOR signaling pathway, thus promoting the maturation and stability of encystation.

Graphical Abstract
Concretizing plan specifications as realizables within the OBO foundry
Authors: Duncan William D. , Diller Matthew , Dooley Damion , Hogan William R. , Beverley John
Published: August 2024

Background

Within the Open Biological and Biomedical Ontology (OBO) Foundry, many ontologies represent the execution of a plan specification as a process in which a realizable entity that concretizes the plan specification, a “realizable concretization” (RC), is realized. This representation, which we call the “RC-account”, provides a straightforward way to relate a plan specification to the entity that bears the realizable concretization and the process that realizes the realizable concretization. However, the adequacy of the RC-account has not been evaluated in the scientific literature. In this manuscript, we provide this evaluation and, thereby, give ontology developers sound reasons to use or not use the RC-account pattern.

Results

Analysis of the RC-account reveals that it is not adequate for representing failed plans. If the realizable concretization is flawed in some way, it is unclear what (if any) relation holds between the realizable entity and the plan specification. If the execution (i.e., realization) of the realizable concretization fails to carry out the actions given in the plan specification, it is unclear under the RC-account how to directly relate the failed execution to the entity carrying out the instructions given in the plan specification. These issues are exacerbated in the presence of changing plans.

Conclusions

We propose two solutions for representing failed plans. The first uses the Common Core Ontologies ‘prescribed by’ relation to connect a plan specification to the entity or process that utilizes the plan specification as a guide. The second, more complex, solution incorporates the process of creating a plan (in the sense of an intention to execute a plan specification) into the representation of executing plan specifications. We hypothesize that the first solution (i.e., use of ‘prescribed by’) is adequate for most situations. However, more research is needed to test this hypothesis as well as explore the other solutions presented in this manuscript.
A quadratic optimization program for the inverse elastography problem
Authors: Barbeiro Sílvia , Henriques Rafael , Santos José Luis
Published: August 2024

In this work we focus on the development of a numerical algorithm for the inverse elastography problem. The goal is to perform an efficient material parameter identification knowing the elastic displacement field induced by a mechanical load. We propose to define the inverse problem through a quadratic optimization program which uses the direct problem formulation to define the objective function. In this way, we end up with a convex minimization problem which attains its minimum at the solution of a linear system. The effectiveness of our method is illustrated through numeral examples.
Barriers to female leadership in intensive care medicine: insights from an ESICM NEXT & Diversity Monitoring Group Survey
Authors: De Rosa Silvia , Schaller Stefan J. , Galarza Laura , Ferrer Ricard , McNicholas Bairbre A. , Bell Max , Helms Julie , Azoulay Elie , Vieillard-Baron Antoine ,   the NEXT Committee & Diversity Monitoring Group of the ESICM Society
Published: August 2024

Background

The underrepresentation of women in leadership remains a pervasive issue, prompting a critical examination of support mechanisms within professional settings. Previous studies have identified challenges women face, ranging from limited visibility to barriers to career advancement. This survey aims to investigate perceptions regarding the effectiveness of women’s leadership programs, mentoring initiatives, and a specialized communication course. Particularly it specifically targets addressing the challenges encountered by professional women.

Methods

This multi-center, observational, international online survey was developed in partnership between ESICM NEXT and the ESICM Diversity and Inclusiveness Monitoring Group for Healthcare. Invitations to participate were distributed to both females and men through emails and social networks. Data were collected from April 1, 2023, through October 1, 2023.

Results

Out of 354 respondents, 90 were men (25.42%) and 264 were women (74.58%). Among them, 251 completed the survey, shedding light on the persistent challenges faced by women in leadership roles, with 10%-50% of respondents holding such positions. Women’s assertiveness is viewed differently, with 65% recognizing barriers such as harassment. Nearly half of the respondent’s experience interruptions in meetings. Only 47.4% receiving conference invitations, with just over half accepting them. A mere 12% spoke at ESICM conferences in the last three years, receiving limited support from directors and colleagues, indicating varied obstacles for female professionals. Encouraging family participation, reducing fees, providing childcare, and offering economic support can enhance conference involvement. Despite 55% applying for ESICM positions, barriers like mobbing, harassment, lack of financial support, childcare, and language barriers were reported. Only 14% had access to paid family leave, while 32% benefited from subsidized childcare. Participation in the Effective Communication Course on Career Advancement Goals and engagement in women’s leadership and mentoring programs could offer valuable insights and growth opportunities. Collaborating with Human Resources and leadership allies is crucial for overcoming barriers and promoting women’s career growth.

Conclusions

The urgency of addressing identified barriers to female leadership in intensive care medicine is underscored by the survey’s comprehensive insights. A multifaceted and intersectional approach, considering sexism, structural barriers, and targeted strategies, is essential.