bluuebunny/crossref_metadata_2025 huggingface dataset:
First International Survey on Diabetes Providers’ Assessment of Skin Reactions in Youth With Type 1 Diabetes Using Technological Devices
Authors: Passanisi Stefano , Berg Anna Korsgaard , Chobot Agata , Dos Santos Tiago Jeronimo , Piona Claudia Anita , Messer Laurel , Lombardo Fortunato ,   ISPAD Jenious Group
Published: October 2023

Background:

Advances in diabetes technological devices led to optimization of diabetes care; however, long-lasting skin exposure to devices may be accompanied by an increasing occurrence of cutaneous reactions.

Methods:

We used an open-link web-based survey to evaluate diabetes-care providers’ viewpoint on prevalence, management practices, and knowledge related to skin reactions with the use of diabetes technological devices. A post hoc analysis was applied to investigate differences in the level of awareness on this topic in relation to the experience in diabetes technology.

Results:

One hundred twenty-five responses from 39 different countries were collected. Most respondents (69%) routinely examine patients’ skin at each visit. All the preventive measures are not clear and, mainly, homogenously put into clinical practice. Contact dermatitis was the most frequently reported cutaneous complication due to diabetes devices, and its most common provocative causes are not yet fully known by diabetes-care providers. Almost half of the respondents (42%) had discussed the presence of harmful allergens contained in adhesives with device manufacturers. There is general agreement on the need to strengthen knowledge on dermatological complications.

Conclusions:

Although diabetes-care providers are quite aware of the chance to develop skin reactions in people with diabetes using technological devices, there are still some unmet needs. Large follow-up studies and further dissemination tools are awaited to address the gaps revealed by our survey.
The Influence of Knee Position on Ultrasound Imaging of Femoral Cartilage in Individuals with Anterior Cruciate Ligament Reconstruction
Authors: Battersby Harry S. , Holmes Skylar C. , Shumski Eric J. , Heredia Caitlyn E. , Garcia Steven A. , Pamukoff Derek N.
Published: October 2023

Background

Articular cartilage is important for knee function and can be imaged using ultrasound. The purpose was to compare femoral cartilage thickness and echo intensity (EI) measured at 90° and 140° of knee flexion and between limbs in a cohort with unilateral anterior cruciate ligament reconstruction (ACLR). We also examined associations between gait biomechanics and cartilage outcomes.

Methods

Twenty-seven individuals with primary unilateral ACLR participated (12 men, 15 women; age = 22.3 ± 3.8 years; time since ACLR = 71.2 ± 47.2 months). Ultrasound was used to obtain femoral cartilage measurements. Gait outcomes included peak KFA (knee flexion angle) and peak external knee flexion moment (KFM). Cartilage outcomes were compared using a 2 ( position) × 2 ( limb) repeated measures ANOVA (analysis of variance). Gait and cartilage associations were assessed using linear regression.

Findings

There were no position × limb interactions for any cartilage outcome (all P > 0.05). Medial ( P = 0.038) and central cartilage ( P < 0.001) were thicker, whereas central ( P = 0.029) and lateral cartilage EI ( P = 0.003) were lower when measured at 90° than those at 140° of knee flexion. Medial cartilage was thicker in the ACLR than that in the contralateral limb ( P = 0.016). A larger KFM was associated with thicker medial cartilage (ΔR2 = 0.146, P = 0.021) and central cartilage (ΔR2 = 0.159, P = 0.039) measured at 140° of knee flexion in the ACLR limb but not at 90°.

Interpretation

Findings suggest that imaging position influences cartilage thickness and EI measurements in individuals with ACLR and should be considered in study designs and clinical evaluation. A greater KFM was associated with thicker cartilage within specific portions of the distal femur.
Infrastructural considerations of implementing gene therapy for hemophilia in the Nordic context
Authors: Astermark Jan , Baghaei Fariba , Strandberg Karin , Toplican Petra Gabric , Birkedal Maj Friberg , Grahn Emma Engman , Hansson Charlotta , Kampmann Peter , Lehtinen Anna-Elina , Täckström Kinga , Holme Pål Andre , Magnusson Maria
Published: October 2023

Background:

Despite improvements in hemophilia care, challenges remain, including treatment burden and impaired quality of life. Gene therapy may overcome these. However, its introduction presents a challenge.

Objectives:

To outline a function-based gene therapy working model describing critical milestones associated with gene therapy handling, administration, and follow-up to facilitate and implement an effective infrastructure for gene therapy introduction.

Design:

Literature review and consensus discussion among Hemophilia Comprehensive Care centers (HCCCs) in the Nordic region.

Methods:

Representatives from six HCCCs sought to pinpoint milestones and key stakeholders for site readiness at the pre-, peri-, and post-infusion stages, including authority and genetically modified organism (GMO) product requirements, awareness, medical eligibility, logistics and product handling for infusion, laboratory monitoring, and follow-up.

Results:

A gene therapy transit map was developed with key stakeholders identified. The approach to prepare the vector will differ between the Nordic centers, but the contracted pharmacy unit will be a key stakeholder. Therefore, a pharmacy checklist for the implementation of gene therapy was developed. For the future, Advanced Therapy Medicinal Product centers will also be implemented. Patients’ expectations, commitments, and concerns need to be addressed repeatedly and education of patients and the expanded health-care professionals team will be the key to successful and optimal clinical management. Eligibility testing according to the product’s summary of product characteristics and frequent follow-up and monitoring post-infusion according to the World Federation of Hemophilia chart will be crucial.

Conclusion:

The approach to deliver gene therapy in the Nordic region will differ partly between the hemophilia centers, but the defined road map with checklists for the implementation of this advanced therapy will be applicable to all. The map may also serve as a platform for the use of future GMO product options both within and outside the area of hemophilia.
An Algorithmically Woven Community: Disclosing Mental Illness and Connecting with Similar Others on an Algorithm-Mediated Platform in China
Authors: Wang Jinping , Qu Jiayu Gina , Leo-Liu Jindong
Published: October 2023

Nowadays, algorithms are extensively used on social platforms for content recommendations and user connections. In this study, through semi-structured interviews with 22 China-based users of RED (i.e., an algorithm-mediated platform similar to TikTok), we investigate how users who have experienced mental illnesses (depression, anxiety, and bipolar disorder) understand RED algorithms and how these algorithms shape their self-disclosure, imagined audience, and community building. Specifically, both the norms of self-disclosure and content recipients are governed by algorithms, while users with limited agency form various folk theories to navigate the process. Moreover, based on accurate content recommendations, the algorithms of RED enable users who have experienced mental illnesses to connect with similar others across the platform. By proposing the concept of an “algorithmically woven community,” we conceptualize and visualize a novel mechanism of how an algorithm works akin to a responsive authority to weave a loosely knit, decentralized, and boundless network.
Student Debt Forgiveness and Economic Stability, Social Mobility, and Quality-of-Life Decisions: Results from a Survey Experiment
Authors: Jabbari Jason , Roll Stephen , Despard Mathieu , Hamilton Leah
Published: October 2023

As policymakers grapple with whether or not to forgive student debt, for who, and how much, it is important to explore how student debt forgiveness would relate to intended household decisions and behaviors. We conducted a survey experiment that asked participants with student debt to imagine a scenario in which the federal government forgave a certain amount of student debt. We then had these participants report on how this would affect their decisions and behaviors. A total of 1,053 participants were randomly assigned to one of four conditions that featured different levels of student debt forgiveness. Our results indicate that student debt is strongly influencing intended decisions and behaviors that can have large implications for household economic stability (e.g., emergency savings) and social mobility (e.g., saving for a down payment on a home). These results also demonstrate that the amount of student debt forgiveness matters.
Atomistic study on the effect of the size of diamond abrasive particle during polishing of stainless steel
Authors: Ranjan Prabhat , Sharma Anuj , Roy Tribeni
Published: October 2023

Nanofinishing or polishing helps to reduce surface roughness, which further improves both the optical and chemical properties of engineering materials. During the polishing of any engineering material, the size of abrasive particles plays a significant role in efficient polishing. In this paper, stainless steel 304 (or SS304) is selected for polishing through diamond abrasives with varying particle sizes using molecular dynamics simulations (MDS). It is found that the diamond abrasive particle initially causes elastic deformation due to the attractive force between the abrasive particle and the workpiece surface. As the size of the abrasive particle increases, plastic deformation occurs by spreading the dislocations on the surface only, which helps to annihilate the dislocations after polishing. It is revealed that the smaller abrasive particles (<3 nm) get trapped due to strong chemical bonding with the surface of the workpiece, and the abrasive particles start depositing on the workpiece instead of material removal. In this paper, it is proposed that an optimum size of abrasive particles is required for a given set of polishing parameters to achieve efficient material removal and minimum surface and subsurface defects. Thus, the present study is worthwhile for efficient polishing or nanocutting of stainless steel through monocrystalline diamond.
Activated Prothrombin Complex Concentrates for the Treatment of Factor Xa Inhibitor-Associated Spontaneous Intracerebral Hemorrhage
Authors: Rowe A. Shaun , Hamilton Leslie A. , Barber Jacob A. , Dinh Theresa , Randolph Allison , Christianson Thomas
Published: October 2023

Background: Anticoagulant-associated intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality. Despite approval of a specific reversal agent for factor Xa inhibitors, there is still much interest in nonspecific reversal agents, such as activated prothrombin complex concentrates (aPCCs). Objective: The objective of this study was to describe ICH expansion in a cohort of patients with factor Xa inhibitor-associated ICH who were treated with aPCC. Methods: This was a retrospective cohort study conducted at an academic medical center designated as a comprehensive stroke center. Consecutive patients admitted for ICH who reported use of apixaban or rivaroxaban prior to admission were considered for inclusion in the study. Patients were treated with 25 to 50 units/kg of aPCC. Intracerebral hemorrhage volume was measured before administration of aPCC and then again within 36 hours of aPCC administration. Results: A total of 40 patients were included in the final analysis. Overall, the cohort was predominantly male (24 [60%]), white (27 [67.5%]), and the mean age was 75.3 ± 10.5 years. Most patients reported taking apixaban prior to admission (31 [77.5%]) and a large proportion were also taking aspirin (13 [32.5%]). The mean change in ICH volume was 1.12 ± 6.03 mL ( P = 0.2475). Conclusions and Relevance: There was a nonsignificant change in mean ICH volume and no reported cases of thromboembolism. Due to the relatively high proportion of patients with significant hematoma expansion, more studies are needed on which patient population would best benefit from treatment with aPCC.
Examining an Interaction Between Plasma Exchange and Apixaban Resulting in an Acute Ischemic Stroke
Authors: Holt Katlyn , Dulgar Katelyn , Reinert Justin P.
Published: October 2023

Objective: Therapeutic drug monitoring is not routinely considered necessary in patients undergoing plasma exchange; however, it is possible for serum concentrations of select medications to be impacted by this procedure. Case: We describe a 50-year-old patient who presented to our facility with new onset aphasia and right-sided weakness. Despite presenting with a National Institute of Health Stroke Severity (NIHSS) score of 23, the patient did not receive fibrinolytic therapy due to his being anticoagulated with apixaban for atrial fibrillation. The patient instead underwent an emergent thrombectomy which resulted in a post-operative Thrombolysis in Cerebral Infarction (TICI) score of 3. The patient had a significant past medical history including numerous previous strokes necessitating assistance with activities of daily living, atrial fibrillation, chronic kidney disease, and thrombocytopenic purpura, for which he was receiving twice weekly plasma exchange and immunomodulatory therapy. The patient’s last plasma exchange session was approximately 24 hours prior to admission, leading us to hypothesize that the patient’s plasma exchange may have been implicated in the removal of apixaban from the serum and precipitating a stroke. Discussion/Conclusions: Heterogeneity of data exists when evaluating the effect of plasma exchange on apixaban. Although the drug properties of apixaban, including its low volume of distribution and high plasma protein binding capacity, support the notion that it may be vulnerable to removal through plasma exchange, only one other case report has been published on this phenomenon.
Toward a Multilevel Framework of Dynamic Capabilities Through the Lens of Project Management, Project Portfolio Management, and Project-Based Organizations
Authors: Barbosa Marcos T. J. , Carvalho Marly M.
Published: October 2023

Project management, project portfolio management (PPM), and project-based organizations (PBOs) literature lacks in approaching the development of dynamic capabilities (DCs). However, creating a competitive advantage through DCs has been considered a valued mechanism. Hence, this study critically reviews the literature, looking for cross-fertilization that bridges the literature on DCs with project management, PPM, and PBOs, using a multilevel perspective to organize the coding book and explore the microfoundations of DCs. Merging content analysis and bibliometrics, we identify 99 DCs clustered into three levels: project management, PPM, and PBOs. It proposes a multilevel framework that classifies the core DCs per level of analysis.
Role of exosomes in the development, diagnosis, prognosis and treatment of hepatocellular carcinoma
Authors: Liu Meijin , Lai Zhonghong , Yuan Xiaoying , Jin Qing , Shen Haibin , Rao Dingyu , Huang Defa
Published: October 2023

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. It is characterized by occult onset resulting in most patients being diagnosed at advanced stages and with poor prognosis. Exosomes are nanoscale vesicles with a lipid bilayer envelope released by various cells under physiological and pathological conditions, which play an important role in the biological information transfer between cells. There is growing evidence that HCC cell-derived exosomes may contribute to the establishment of a favorable microenvironment that supports cancer cell proliferation, invasion, and metastasis. These exosomes not only provide a versatile platform for diagnosis but also serve as a vehicle for drug delivery. In this paper, we review the role of exosomes involved in the proliferation, migration, and metastasis of HCC and describe their application in HCC diagnosis and treatment. We also discuss the prospects of exosome application in HCC and the research challenges.
Association between tooth loss and frailty among Chinese older adults: the mediating role of dietary diversity
Authors: Xu Xin , Zhao Yuan , Wu Bei , Pei Yaolin , Gu Danan
Published: October 2023

Background

This study aimed to examine the association between tooth loss and frailty among Chinese older adults and the mediating role of dietary diversity in this association.

Methods

Data from five waves of the Chinese Longitudinal Healthy Longevity Survey conducted between 2005 and 2018 were used. Path analyses were employed to assess both concurrent and cross-lagged relationships between tooth loss and frailty index while accounting for intrapersonal correlation. Furthermore, the mediation effect of dietary diversity was also examined.

Results

In concurrent models, severe tooth loss was associated with frailty after adjusting for demographic characteristics (odds ratio [OR] = 1.82, p < 0.001). The OR of frailty for severe tooth loss was only slightly decreased to 1.74 (p < 0.001) when dietary diversity was added to the model and to 1.64 (p < 0.001) when socioeconomic status, family support, and healthy lifestyles were further adjusted. In the cross-lag or longitudinal models, the ORs were mildly or moderately reduced to 1.29, 1.27, and 1.23, respectively, yet remained statistically significant (p < 0.001 or p < 0.01). The mediation analyses showed that dietary diversity had some small yet significant effects on the relationship between tooth loss and frailty in both concurrent and longitudinal settings.

Conclusions

This study improves current knowledge regarding the impact of tooth loss on frailty among Chinese older adults. Future intervention strategies designed to improve healthy diets may have preventive effects against the risk of frailty among Chinese older adults with severe tooth loss.
Risk factor analysis of the development of severe radiation pneumonitis in patients with non-small cell lung cancer treated with curative radiotherapy, with focus on underlying pulmonary disease
Authors: Kim Hakyoung , Hwang Jeongeun , Kim Sun Myung , Choi Juwhan , Yang Dae Sik
Published: October 2023

Background

We aim to identify the multifaceted risk factors that can affect the development of severe radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) treated with curative high-dose radiotherapy with or without concurrent chemotherapy.

Methods

We retrospectively reviewed the medical records of 175 patients with stage-I-III NSCLC treated with curative thoracic X-ray radiotherapy at the Korea University Guro Hospital between June 2019 and June 2022. Treatment-related complications were evaluated using the Common Terminology Criteria for Adverse Events (version 4.03).

Results

The median follow-up duration was 15 months (range: 3–47 months). Idiopathic pulmonary fibrosis (IPF) as an underlying lung disease (P < 0.001) and clinical stage, regarded as the concurrent use of chemotherapy (P = 0.009), were associated with a high rate of severe RP. In multivariate analyses adjusting confounding variables, the presence of IPF as an underlying disease was significantly associated with severe RP (odds ratio [95% confidence interval] = 48.4 [9.09–347]; P < 0.001). In a subgroup analysis of stage-I-II NSCLC, the incidence of severe RP in the control, chronic obstructive pulmonary disease (COPD), and IPF groups was 3.2%, 4.3%, and 42.9%, respectively (P < 0.001). The incidence of severe RP was 15.2%, 10.7%, and 75.0% in the control, COPD, and IPF groups, respectively (P < 0.001) in the stage-III NSCLC group.

Conclusions

This study revealed that IPF as an underlying lung disease and the concurrent use of chemotherapy are associated with a high rate of severe RP. In contrast, COPD did not increase the risk of pulmonary toxicity after receiving curative high-dose radiotherapy.
Association between bullying victimization and post-traumatic stress disorders among Chinese adolescents: a multiple mediation model
Authors: Li Tianchang , Chen Bo , Li Qian , Wu Xinyue , Li Yifan , Zhen Rui
Published: October 2023

Background

Research that focused on the mechanisms underlying the relation between school bullying victimization and PTSD ignored the simultaneous effect of emotional and cognitive factors, which may limit our comprehensive understanding of their roles. Besides, most researchers included non-bullying victims in data analysis, and this may mask the true effect among bullying victims. The present study aimed to explore the relation between bullying victimization and PTSD, and the mediating roles of social anxiety, loneliness, and rumination, after filtering out non-bullying victims.

Materials and methods

In April 2019, we used convenience sampling to recruit 5013 students from Grade 10 and 11 in two high schools in Anhui Province, China. The mean age of these students was 16.77 (SD = 0.92) years. They completed five self-report questionnaires including the Delaware Bullying Victimization Scale-Student Chinese Revision (DBVS-S), the modified PTSD Checklist, the Social Anxiety Scale, the Adolescent Loneliness Scale, and the Rumination Scale. Further, a total of 443 bullying victims were screened out for this study according to the critical score of the DBVS-S.

Results

The results showed that bullying victimization had a direct and positive association with PTSD among adolescents (β = 0.16, 95%CI: 0.046–0.252). Bullying victimization was positively associated with PTSD through increasing adolescents’ social anxiety (β = 0.06, 95%CI: 0.017–0.105), as well as through increasing their loneliness (β = 0.16, 95%CI: 0.109–0.215). In addition, bullying victimization was positively associated with PTSD through social anxiety via loneliness (β = 0.04, 95%CI: 0.013–0.067), as well as through loneliness via rumination (β = 0.02, 95%CI: 0.003–0.033). Bullying victimization was also positively associated with PTSD through a three-step path from social anxiety to rumination via loneliness (β = 0.004, 95%CI: 0.001–0.009).

Conclusions

Social anxiety, loneliness, and rumination have important mediating effects in the relation between bullying victimization and adolescents’ PTSD, in which emotional factors (e.g., social anxiety, loneliness) are more crucial than cognitive factors (e.g., rumination). Intervention should pay more attention to timely alleviate victims’ emotional problems to reduce the risk of developing PTSD.
Barriers to implementing health programs based on community participation: the Q method derived perspectives of healthcare professional
Authors: Mahmoodi Hassan , Bolbanabad Amjad Mohamadi , Shaghaghi Abdolreza , Zokaie Mehdi , Gheshlagh Reza Ghanei , Afkhamzadeh Abdorrahim
Published: October 2023

Background

Community participation in implementing health programs leads to positive organizational, social and individual consequences. This study aimed to investigate the prospects of a sample of Iranian healthcare professionals about their perceived barriers to implementing health programs based on community participation.

Methods

This was a cross-sectional study that employed a Q-methodology approach. Twenty health professional sorted the 47 statements into a 9-column Q-sort diagram ranging from − 4 as not important to + 4 as very important. The data were analyzed with PQMethod 2.35 software. The centroid factor analysis and varimax rotation were used for data analysis. Factors identified were interpreted and described in terms of the participants perspectives on the phenomenon.

Results

Analysis of the study participants’ viewpoints (the Q-sorts) resulted in a five factor solution (accounted for 57% of the total variance) to endorse the main barriers to the implementation of health programs based on community participation in Iran. Barriers related to government, health programs, lack of necessary skills amongst health professionals and weak coordination between departments, barriers related to community, lack of understanding of goals, benefits and transparency of roles and responsibilities were among the important emanated factors to implementing health programs based community participation.

Conclusion

Health policymakers and managers should consider the five mentioned identified barriers based on the community when planning and implementing the health program participation and try to empower the community to implement the programs in Iran.
Application of laparoscopic backtracking full-thickness continuous everting suture for non-AOSC choledocholithiasis
Authors: Yuan Bo , Zhang Xuanfeng , Kong Chenchen , Zhang Cancan , Li Huansong
Published: October 2023

Background

Based on the current trend of increasing incidence of choledocholithiasis, it is of great significance to explore the closure method of the common bile duct during laparoscopic choledocholithotomy.

Methods

Backtracking full-thickness continuous everting suture was selected for primary closure of the common bile duct suture, while traditional T-tube drainage was selected for the control group. Propensity score matching (PSM) was used to reduce baseline differences between the two groups.

Result

The intraoperative blood loss, operation time, postoperative recovery speed, postoperative bleeding, postoperative pancreatitis, recurrence rate of bile duct stones, and hospitalization time in the primary closure group were all less than those in the T-tube drainage group.

Conclusion

Under certain conditions, backtracking full-thickness continuous everting suture could benefit patients with choledocholithiasis compared with traditional T-tube drainage.
Formal support services and (dis)empowerment of domestic violence victims: perspectives from women survivors in Ghana
Authors: Kaburi Ruth Minikuubu , Kaburi Basil Benduri
Published: October 2023

Background

As part of efforts to prevent violence against women, several countries have institutionalized formal support services including legislations to prevent, protect victims, and deter perpetrators of domestic violence (DV). Prior research on formal support service utilization shows that DV survivors do not get the necessary services they deserve. However, much remains to be known about the experiences of women survivors of DV who accessed a range of formal support services and how their experiences (dis)empowered them. Here, we assessed the experiences of Ghanaian women survivors of DV with formal support services vis-à-vis the provisions of the Ghana DV Act and insights of subject experts.

Methods

From May to August 2018, we recruited a total of 28 participants: 21 women survivors of DV in Weija-Gbawe Municipality of Ghana, and 7 experts from the police, human rights, and health professions. We used two sets of in-depth interview guides: one to collect data on survivors’ experiences, and the second for the insights of experts. We performed summary descriptive statistics on survivors’ sociodemographic characteristics and used thematic analysis to assess their experiences of DV; and access to, patronage, and response of formal support services.

Results

Of 21 DV survivors, 19 (90.1%) were aware of the existence of the DV law, however none was well informed of their entitlements. DV survivors have low formal education and are not economically empowered. Some DV survivors are revictimized in the process of accessing formal services. DV survivors expect the government to provide them with shelter, upkeep, medical, and legal aid. All the 21 survivors had at least one contact with a women’s rights organization and were knowledgeable of their supporting services namely legal services, temporary shelter, and psychosocial support.

Conclusions

The experiences of DV survivors do not reflect the legal provisions of Ghana’s DV Act. Government under funding of formal services and negative gender norms are disempowering to survivors. NGOs are popular among women survivors of DV in Ghana for the education, legal, and material support they provide. A close collaboration between the government and NGOs could better mitigate DV in Ghana.
Family physicians partnering for system change: a multiple-case study of Ontario Health Teams in development
Authors: Grady Colleen , Chan-Nguyen Sophy , Mathies David , Alam Nadia
Published: October 2023

Background

The Ontario Health Team (OHT) model is a form of integrated care that seeks to provide coordinated delivery of care to communities across Ontario, Canada. Primary care is positioned at the heart of the OHT model, yet physician participation and representation has been severely challenged at planning and governance tables. The purpose of this multiple case study is to examine (1) processes and structures to enable family physician participation in OHTs and (2) describe challenges to family physician participation.

Methods

We chose a qualitative, exploratory multiple-case study approach following Yin’s design and methods. The study took place between June and December 2021.We conducted semi-structured interviews with OHT stakeholders in four communities and carried out an analysis of internal and external documents to contextualize interview findings. Thematic analysis was applied within case and between cases.

Results

Four OHTs participated in this study with thirty-nine participants (17 family physicians; 22 other stakeholders). Over 60 documents were analyzed. Within-case analysis found that structures and processes should be formalized and established to facilitate physician participation. Skepticism, burnout, heavy workload, and the COVID-19 pandemic were challenges to participation. Between-case analysis found that participation varied. Face-to-face communication processes were favoured in all cases and history of collaboration facilitated relationship-building. All cases faced similar challenges to physician participation despite regional differences.

Conclusions

The implementation of OHTs demonstrates that integrated care models can address critical health system issues through a collective approach. Physician participation is vital to the development of an OHT, however, recognition of their challenges (skepticism, burnout, COVID-19 pandemic) to participating must be acknowledged first. To ensure that models like OHTs thrive, physicians must be meaningfully engaged in various aspects and levels of governance and delivery.
Accessibility crisis of essential medicines at Sudanese primary healthcare facilities: a cross-sectional drugs’ dispensaries assessment and patients’ perspectives
Authors: Hemmeda Lina , Koko Abubaker E. A. , Mohamed Radia F. , Mohammed Yousra Ibrahim Abdallah , Elabid Abeer Osman Mukhtar , Omer Alaa T. , Hamida Amna Abdel Rafea Al Hashemi , Haiba Aya M. , Ali Eithar M. , Abdelgadir Istabraq I. , Al Fanob Reem M. , Almahadi Saja S. Mohamed , Ali Sara , Mahgoub Suzan A. A
Published: October 2023

Background

Access to essential medicines is a critical component of universal health coverage. However, the availability of essential medicines in Sudan isn’t well studied. As well, most Sudanese people lack health insurance, making out-of-pocket spending the primary source of drug financing. Therefore, the affordability of medicines in Sudan is questionable, with only 30% of the total population being covered by a public health service or public health insurance. We undertook this study to assess the availability and prices of essential medicines in public-sector health facilities in Khartoum state. Moreover, this study aims at assessing patients’ perceived affordability of essential medicines, and accommodation and acceptability of the public facility.

Methods

A cross-sectional study was carried out at 30 primary healthcare facilities’ drug dispensaries across three districts in Khartoum state. Within each Centre’s dispensary unit, a standardized checklist evaluated the availability and affordability of 21 essential medicines selected from Sudan’s national essential medicines list and assessed their storage conditions. Furthermore, 630 patients were selected from all dispensary units for an exit interview that assessed their perceived accessibility, acceptability, accommodation, and affordability of essential medicines. Data were collected through the Kobo toolbox and analyzed using SPSS version 26.

Results

Participants’ ratings of accessibility, affordability, accommodation, and acceptability were 3.7/5, 1.5/4, 5/6, and 5.4/6, respectively, with a 26.7% full access and weak correlation between some of the indices. The overall availability of adults and pediatric medicines was 36.8% 6.7%, respectively. Cost of a single course of treatment for 10 and 16 drugs out of the 19 drugs consumed exceeds the daily wage of insured and uninsured patients, with a median price ratio of 16.4 and 62.8, respectively. Moreover, the dispensary area conditions were found to be of good quality, yet the storerooms were not functioning in 40% of the outlets.

Conclusion

Patients had limited access to their needed drugs due to high prices and physical unavailability, and primary healthcare capacities are not meeting the demands of citizens. The outcomes for the patients’ access variables (accessibility, accommodation, acceptance, and affordability) are comparable to those in countries with low incomes. Ensuring access to free medicines is likely to improve patients’ satisfaction with healthcare services and reduce private expenditure on medicines, which is a long-term, sustainable way towards universal health coverage in Sudan.
Development and evaluation of a culturally adapted digital-platform integrated multifaceted intervention to promote the utilization of maternal healthcare services: a single-arm pilot study
Authors: Xu Jiayao , Akezhuoli Hailati , Zhou Meng , Yao Tingting , Lu Jingjing , Wang Xiaomin , Zhou Xudong
Published: October 2023

Background

The utilization of hospital delivery and antenatal care (ANC) is essential for improving maternal and newborn outcomes. However, social and cultural barriers in underdeveloped rural areas hindered maternal care utilization. This study aims to design and evaluate the effectiveness of a culturally adapted digital-platform intervention to promote maternal care utilization among women in ethnic minority communities in China.

Methods

From January 1st, 2020, to December 31st, 2021, all pregnant women in Mianshan town, Liangshan Autonomous Prefecture, were invited to participate in the intervention. The multifaceted intervention included participatory and cultural-tailored health education on a popular social media platform, transportation subsidies, and capacity building and economic incentives for healthcare providers. The effectiveness of the intervention was evaluated by comparing two groups: mothers who gave live birth before the intervention (January 1st to December 31st, 2019) and mothers whose entire pregnancy period was covered by the intervention. The primary outcomes were the rate of hospital delivery and ANC utilization. Data on pregnant women were retrospectively collected through telephone surveys and the maternal and newborn’s health monitoring system.

Results

A total of 237 intervention sample and 138 pre-intervention sample were included. The intervention group demonstrated significantly higher rates of hospital delivery (97.5% vs. 87.7%, p < 0.001), timely initiation of ANC (73.0% vs. 62.3%, p = 0.031), and timely completion of five-time ANC visits (37.1% vs.4.3%, p < 0.001) compared to the pre-intervention group. The intervention group was more likely to utilize hospital delivery (OR = 9.26, 95%CI [2.83–30.24], p < 0.001) and ANC, including timely initiation of ANC (OR = 2.18, 95%CI [1.31–3.62], p = 0.003), completion of five ANC visits (OR = 1.72, 95%CI [1.05–2.83], p = 0.032), and timely completion of five ANC visits (OR = 15.12, 95%CI [6.24–36.64], p < 0.001).

Conclusions

The culturally adapted digital-platform integrated multifaceted intervention effectively promoted the utilization of hospital delivery, timely initiation of ANC, and completion of ANC visits in the Yi ethnic community in China. This study provides valuable insights for future interventions targeting maternal healthcare services in underdeveloped ethnic minority communities worldwide.

Trial registration

Chinese Clinical Trial Registry, ChiCTR2300073219. Registered 4 July 2023 - Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=199202.
Examining buprenorphine diversion through a harm reduction lens: an agent-based modeling study
Authors: Adams Joëlla W. , Duprey Michael , Khan Sazid , Cance Jessica , Rice Donald P. , Bobashev Georgiy
Published: October 2023

Background

Recent policies have lessened restrictions around prescribing buprenorphine-naloxone (buprenorphine) for the treatment of opioid use disorder (OUD). The primary concern expressed by critics of these policies is the potential for buprenorphine diversion. However, the population-level effects of increased buprenorphine diversion are unclear. If replacing the use of heroin or fentanyl, use of diverted buprenorphine could be protective.

Methods

Our study aim was to estimate the impact of buprenorphine diversion on opioid overdose using an agent-based model calibrated to North Carolina. We simulated the progression of opioid misuse and opioid-related outcomes over a 5-year period. Our status quo scenario assumed that 50% of those prescribed buprenorphine diverted at least one dose per week to other individuals with OUD and 10% of individuals with OUD used diverted buprenorphine at least once per week. A controlled prescription only scenario assumed that no buprenorphine would be diverted, while an increased diversion scenario assumed that 95% of those prescribed buprenorphine diverted and 50% of individuals with OUD used diverted buprenorphine. We assumed that use of diverted buprenorphine replaced the use of other opioids for that day. Sensitivity analyses increased the risk of overdose when using diverted buprenorphine, increased the frequency of diverted buprenorphine use, and simulated use of diverted buprenorphine by opioid-naïve individuals. Scenarios were compared on opioid overdose-related outcomes over the 5-year period.

Results

Our status quo scenario predicted 10,658 (credible interval [CI]: 9699–11,679) fatal opioid overdoses. A scenario simulating controlled prescription only of buprenorphine (i.e., no diversion) resulted in 10,741 (9895–11,650) fatal opioid overdoses versus 10,301 (9439–11,244) within a scenario simulating increased diversion. Compared to the status quo, the controlled prescription only scenario resulted in a similar number of fatal overdoses, while the scenario with increased diversion of buprenorphine resulted in 357 (3.35%) fewer fatal overdoses. Even when increasing overdose risk while using diverted buprenorphine and incorporating use by opioid naïve individuals, increased diversion did not increase overdoses compared to a scenario with no buprenorphine diversion.

Conclusions

A similar number of opioid overdoses occurred under modeling conditions with increased rates of buprenorphine diversion among persons with OUD, with non-statistical trends toward lower opioid overdoses. These results support existing calls for low- to no-barrier access to buprenorphine for persons with OUD.
Genetic assessment of pathogenic germline alterations in lysosomal genes among Asian patients with pancreatic ductal adenocarcinoma
Authors: Koh Youngil , Kim Hyemin , Joo So Young , Song Seulki , Choi Young Hoon , Kim Hyung Rae , Moon Byul , Byun Jamin , Hong Junshik , Shin Dong-Yeop , Park Solip , Lee Kwang Hyuck , Lee Kyu Taek , Lee Jong Kyun , Park Daechan , Lee Se-Hoon , Jang Jin-Young , Lee Hyunsook , Kim Jung-Ae , Yoon Sung-Soo , Park Joo Kyung
Published: October 2023

Background

Lysosomes are closely linked to autophagic activity, which plays a vital role in pancreatic ductal adenocarcinoma (PDAC) biology. The survival of PDAC patients is still poor, and the identification of novel genetic factors for prognosis and treatment is highly required to prevent PDAC-related deaths. This study investigated the germline variants related to lysosomal dysfunction in patients with PDAC and to analyze whether they contribute to the development of PDAC.

Methods

The germline putative pathogenic variants (PPV) in genes involved in lysosomal storage disease (LSD) was compared between patients with PDAC (n = 418) and healthy controls (n = 845) using targeted panel and whole-exome sequencing. Furthermore, pancreatic organoids from wild-type and KrasG12D mice were used to evaluate the effect of lysosomal dysfunction on PDAC development. RNA sequencing (RNA-seq) analysis was performed with established PDAC patient-derived organoids (PDOs) according to the PPV status.

Results

The PPV in LSD-related genes was higher in patients with PDAC than in healthy controls (8.13 vs. 4.26%, Log2 OR = 1.65, P = 3.08 × 10–3). The PPV carriers of LSD-related genes with PDAC were significantly younger than the non-carriers (mean age 61.5 vs. 65.3 years, P = 0.031). We further studied a variant of the lysosomal enzyme, galactosylceramidase (GALC), which was the most frequently detected LSD variant in our cohort. Autophagolysosomal activity was hampered when GALC was downregulated, which was accompanied by paradoxically elevated autophagic flux. Furthermore, the number of proliferating Ki-67+ cells increased significantly in pancreatic organoids derived from Galc knockout KrasG12D mice. Moreover, GALC PPV carriers tended to show drug resistance in both PDAC cell line and PDAC PDO, and RNA-seq analysis revealed that various metabolism and gene repair pathways were upregulated in PDAC PDOs harboring a GALC variant.

Conclusions

Genetically defined lysosomal dysfunction is frequently observed in patients with young-onset PDAC. This might contribute to PDAC development by altering metabolism and impairing autophagolysosomal activity, which could be potentially implicated in therapeutic applications for PDAC.
The HIFIA/LINC02913/IGF1R axis promotes the cell function of adipose-derived mesenchymal stem cells under hypoxia via activating the PI3K/AKT pathway
Authors: Xiong Xiang , Yuan Liqin , Yang Kai , Wang Xiancheng
Published: October 2023

Objective

Promoting angiogenesis is crucial for tissue repair. Adipose-derived mesenchymal stem cells (ADSCs) are endowed with the ability of paracrine secretion of various angiogenic cytokines and the differentiation potential into endothelium-like cells to directly participate in angiogenesis. ADSCs are key seed cells for promoting angiogenesis in regenerative medicine and tissue engineering. This study aimed to explore the role and mechanism of C9orf106 (LINC02913) in the angiogenesis of ADSCs.

Methods

The microarray dataset GSE12884 was analyzed to identify the differentially expressed lncRNAs in ADSCs under normoxia and hypoxia. The expression of the key genes was detected using qRT-PCR, western blot assay (western blot), and immunofluorescence (IF) staining. The adipogenic ability and tube formation ability of ADSCs was detected using oil red O staining and tube formation assay, respectively. The regulatory relationship between hypoxia-inducible factor-1alpha (HIF1A) and LINC02913 was verified using chromatin immunoprecipitation (ChIP) assay and dual-luciferase reporter gene assay. A skin wound healing nude mice model was established. Hematoxylin and eosin (H&E) staining was applied to detect pathological skin damage. Immunohistochemistry (IHC) staining was used to determine the level of CD31 in skin tissues.

Results

LINC02913 expression was decreased in ADSCs under hypoxia; LINC02913 overexpression inhibited the proliferation, adipogenic ability, endothelial differentiation ability, and tube formation ability of ADSCs. ChIP assay and dual-luciferase reporter gene assay results showed that HIF1A could directly bind to the LINC02913 promoter region to inhibit its transcription. Through RNAact prediction and analysis of the correlation with LINC02913 expression, it was found that IGF1R may directly interact with LINCO02913. The HIF1A/LINC02913/IGF1R axis could activate the PI3K/AKT pathway to promote the biological function of ADSCs. Hypoxia-ADSCs significantly promoted vascularization in the wounded skin. The regulatory effect of LINC02913/IGF1R axis on hypoxia-ADSCs treated skin wound healing were verified.

Conclusion

The HIF1A/LINC02913/IGF1R axis promoted the proliferation, adipogenic ability, and tube formation ability of ADSCs under hypoxia via activating the PI3K/AKT pathway.
Acellular ex vivo lung perfusate silences pro-inflammatory signaling in human lung endothelial and epithelial cells
Authors: Jeon Jamie E. , Huang Lei , Zhu Zhiyuan , Wong Aaron , Keshavjee Shaf , Liu Mingyao
Published: October 2023

Background

Ischemia–reperfusion injury is a key complication following lung transplantation. The clinical application of ex vivo lung perfusion (EVLP) to assess donor lung function has significantly increased the utilization of “marginal” donor lungs with good clinical outcomes. The potential of EVLP on improving organ quality and ameliorating ischemia–reperfusion injury has been suggested.

Methods

To determine the effects of ischemia–reperfusion and EVLP on gene expression in human pulmonary microvascular endothelial cells and epithelial cells, cell culture models were used to simulate cold ischemia (4 °C for 18 h) followed by either warm reperfusion (DMEM + 10% FBS) or EVLP (acellular Steen solution) at 37 °C for 4 h. RNA samples were extracted for bulk RNA sequencing, and data were analyzed for significant differentially expressed genes and pathways.

Results

Endothelial and epithelial cells showed significant changes in gene expressions after ischemia–reperfusion or EVLP. Ischemia–reperfusion models of both cell types showed upregulated pro-inflammatory and downregulated cell metabolism pathways. EVLP models, on the other hand, exhibited downregulation of cell metabolism, without any inflammatory signals.

Conclusion

The commonly used acellular EVLP perfusate, Steen solution, silenced the activation of pro-inflammatory signaling in both human lung endothelial and epithelial cells, potentially through the lack of serum components. This finding could establish the basic groundwork of studying the benefits of EVLP perfusate as seen from current clinical practice.