bluuebunny/crossref_metadata_2025_split huggingface dataset:
Healthcare utilization, costs, and productivity losses in treatment-resistant depression in Finland – a matched cohort study
Authors: Taipale Heidi , Lähteenvuo Markku , Tanskanen Antti , Huoponen Saara , Rannanpää Saara , Tiihonen Jari 
Published: July 2022

Abstract
Background
Due to its relatively high prevalence and recurrent nature, depression causes a major burden on healthcare systems, societies and individuals. Our objective was to investigate healthcare resource utilization and costs associated with treatment-resistant depression (TRD) compared with non-treatment-resistant depression in Finland.

Methods
Of all patients aged 16–65 years and diagnosed with depression in Finland during 2004–2016, persons with TRD (N = 15,405) were identified from nationwide registers and matched 1:1 with comparison persons with depression who initiated antidepressant use but did not have TRD at the time of matching. TRD was defined as initiation of a third treatment trial after having failed two pharmacological treatment trials. Follow-up period covered 5 years after TRD or corresponding matching date (until end of 2018). Health care resource utilization was studied with negative binomial regression and costs of TRD (per patient per year) with generalized estimating equations, by adjusting for baseline costs, comorbidity and baseline severity of depression.

Results
Persons with TRD (mean age 38.7, SD 13.1, 60.0% women) had more health care utilization and work disability (sick leaves and disability pensions), adjusted incidence rate ratio for work disability days was 1.72 (95% CI 1.64–1.80). This resulted in 1.9-fold higher total costs for persons with TRD (15,907 versus 8335 EUR), adjusted mean difference 7572 (95% CI 7215–7929) EUR per patient per year, higher productivity losses (due to sick leaves and disability pensions, mean difference 5296, 95% CI 5042–5550), and direct healthcare costs (2003, 95% CI 1853–2151) compared with non-TRD patients. Mean difference was the highest during the first year after TRD (total costs difference 11,760, 95% CI 11,314–12,206) and the difference decreased gradually after that.

Conclusion
Treatment-resistant depression is associated with about two-fold cost burden compared with non-treatment-resistant depression.
A typical presentation of moxifloxacin-induced DRESS syndrome with pulmonary involvement: a case report and review of the literature
Authors: Zhang Yinhong , Wang Xiaoyan , Cheng Yang , Wang Xiaofang , Zhang Yunjian 
Published: July 2022

Abstract
Background
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a kind of hypersensitivity drug reaction involving the skin and multiple internal organ systems. Moxifloxacin has rarely been reported to be a drug that is associated with DRESS syndrome. Lungs are less frequently involved in DRESS syndrome, but their involvements may herald more serious clinical processes. We present a rare typical case of moxifloxacin-induced DRESS syndrome with lungs involved. Valuable clinical data such as changes in the pulmonary imaging and pulmonary function tests was recorded. This case is important for the differential diagnosis of DRESS syndrome with lungs involved by providing clinical manifestations, CT imaging, pulmonary function tests, and biopsy pathological characteristics. The changes in pulmonary imaging and pulmonary function tests may help us understand the mechanism of DRESS syndrome further.

Case presentation
We report a case of a 47-year-old woman who was treated with oral moxifloxacin for community-acquired pneumonia. The patient subsequently developed a cough, fever, liver injury, skin rash, hematologic abnormalities, and shortness of breath (SOB) followed by pharyngeal herpes and peripheral neuritis. These symptoms, clinical lab index, and CT scan of the lungs improved after the withdrawal of moxifloxacin. The probability of moxifloxacin-induced DRESS syndrome was rated as “Definite”, with 7 scores graded by RegiSCAR. A literature search was also performed with “fluoroquinolones,” “moxifloxacin,” “ciprofloxacin,” “levofloxacin,” “delafloxacin,” and “DRESS” or “drug-induced hypersensitivity syndrome (DIHS)” as the keywords that were put into PubMed. The overall pulmonary involvement was approximately 9.1% (1/11). It is a rare reported case of DRESS syndrome with pulmonary involvement induced by moxifloxacin. We summarized detailed clinical data, including pulmonary imaging and pulmonary function changes.

Conclusion
This is a rare reported case of DRESS syndrome with pulmonary involvement induced by moxifloxacin. Prompt recognition and correct diagnosis can promote appropriate treatment and accelerate recovery. This case is important for us as a reference in the differential diagnosis of DRESS syndrome and helps us further understand the mechanism of DRESS syndrome.
Sodium butyrate inhibits osteogenesis in human periodontal ligament stem cells by suppressing smad1 expression
Authors: Hou Jingyi , Xu Junji , Liu Yi , Zhang Haiping , Wang Sihan , Jiao Yao , Guo Lijia , Li Song 
Published: July 2022

Abstract
Background
Butyrate is a major subgingival microbial metabolite that is closely related to periodontal disease. It affects the proliferation and differentiation of mesenchymal stem cells. However, the mechanisms by which butyrate affects the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) remain unclear. Here, we investigated the effect of sodium butyrate (NaB) on the osteogenic differentiation of human PDLSCs.

Methods
PDLSCs were isolated from human periodontal ligaments and treated with various concentrations of NaB in vitro. The cell counting kit-8 assay and flow cytometric analysis were used to assess cell viability. The osteogenic differentiation capabilities of PDLSCs were evaluated using the alkaline phosphatase activity assay, alizarin red staining, RT-PCR, western blotting and in vivo transplantation.

Results
NaB decreased PDLSC proliferation and induced apoptosis in a dose- and time-depend manner. Additionally, 1 mM NaB reduced alkaline phosphatase activity, mineralization ability, and the expression of osteogenic differentiation-related genes and proteins. Treatment with a free fatty acids receptor 2 (FFAR2) antagonist and agonist indicated that NaB inhibited the osteogenic differentiation capacity of PDLSCs by affecting the expression of Smad1.

Conclusion
Our findings suggest that NaB inhibits the osteogenic differentiation of PDLSCs by activating FFAR2 and decreasing the expression of Smad1.
Assessment of the association of OCT3/4 with GLUT1 and CD105 in oral squamous cell carcinoma using dual immunohistochemistry
Authors: Derakhshan Samira , Mahdavi Nazanin , Kardouni Khoozestani Neda , Nasr Esfahani Bita , Heidarian Foroozan , Rahrotaban Sedigheh , Abdolrahmani Ali 
Published: July 2022

Abstract
Background
Oral squamous cell carcinoma (OSCC) is the most common cancer affecting the oral and maxillofacial region. This study aimed to investigate the role of cancer stem cells (CSCs) in angiogenesis and hypoxic response in OSCC.

Methods
This retrospective observational study evaluated 56 cases of OSCC using dual immunohistochemistry. Octamer-binding transcription factor 3/4 (OCT3/4) marker was used to evaluate CSC activity. Glucose transporter 1 (GLUT1) marker was used to evaluate the hypoxic response and angiogenesis, while endoglin (CD105) was used to evaluate the late stage of angiogenesis and blood vessel formation.

Results
Co-expression of OCT3/4 and GLUT1 was noted in 11 of 12 patients with grade III OSCC. However, we did not observe co-expression of these markers in 13 of 22 patients with grade I OSCC. Although we observed a significant correlation between co-expression of GLUT1 and OCT3/4 and tumor grade, there was no significant correlation between co-expression of OCT3/4 and CD105 and different grades of OSCC.

Conclusions
CSCs could play important roles in the initial stages of hypoxic response and angiogenesis. Our result reported that in higher grades of OSCC, GLUT1 as a first response to hypoxic situations might be a result of CSCs. Further studies are required to discover other biomarkers, their roles, and associated pathways of CSCs in OSCC.
The impact of COVID-19 on medical students’ practical skills and hygiene behavior regarding venipuncture: a case control study
Authors: Meyer Annika , Stosch Christoph , Klatt Andreas R. , Streichert Thomas 
Published: July 2022

Abstract
Background
Despite their importance to current and future patient care, medical students’ hygiene behaviors and acquisition of practical skills have rarely been studied in previous observational study. Thus, the aim of this study was to investigate the potential impact of the COVID-19 pandemic on medical student’s hygiene and practical skills.

Methods
This case-control study assessed the effect of the COVID-19 pandemic on hygiene behavior by contrasting the practical skills and hygiene adherence of 371 medical students post the pandemic associated lockdown in March 2020 with that of 355 medical students prior to the SARS-CoV-2 outbreak. Students’ skills were assessed using an objective structured clinical examination (OSCE). Their skills were then compared based on their results in hygienic venipuncture and the total OSCE score.

Results
During the SARS-CoV-2 pandemic, medical students demonstrated an increased level of compliance regarding hand hygiene before (prior COVID-19: 83.7%; during COVID-19: 94.9%; p < 0.001) and after patient contact (prior COVID-19: 19.4%; during COVID-19: 57.2%; p = 0.000) as well as disinfecting the puncture site correctly (prior COVID-19: 83.4%; during COVID-19: 92.7%; p < 0.001). Prior to the pandemic, students were more proficient in practical skills, such as initial venipuncture (prior COVID-19: 47.6%; during COVID-19: 38%; p < 0.041), patient communication (prior COVID-19: 85.9%; during COVID-19: 74.1%; p < 0.001) and structuring their work process (prior COVID-19: 74.4%; during COVID-19: 67.4%; p < 0.024).

Conclusion
Overall, the COVID-19 pandemic sensitized medical students’ attention and adherence to hygiene requirements, while simultaneously reducing the amount of practice opportunities, thus negatively affecting their practical skills. The latter development may have to be addressed by providing additional practice opportunities for students as soon as the pandemic situation allows.
Relationship between medical students’ perceived instructor role and their approaches to using online learning technologies in a cloud-based virtual classroom
Authors: Wang Rong , Han Jiying , Liu Chuanyong , Wang Lixiang 
Published: July 2022

AbstractBackgroundStudents can take different approaches to using online learning technologies: deep and surface. It is important to understand the relationship between instructor role and student approaches to using online learning technologies in online learning settings supported by cloud computing techniques.MethodsA descriptive, cross-sectional study was conducted to analyze the relationships between medical students’ perceptions of instructor role (instructor support, instructor-student interaction, and instructor innovation) and students’ approaches to using online learning technologies in cloud-based virtual classrooms. A 25-item online questionnaire along with a sheet with basic demographic was administered to all medical students at Qilu Medical Schools of Shandong University China. Overall, 213 of 4000 medical students (5.34%) at the medical school participated in the survey.ResultsThe results showed high levels of medical students’ perceived instructor support, instructor-student interaction and instructor innovation. Most students adopted the deep approaches to using online learning technologies. Instructor support, instructor-student interaction and innovation were positively related to students’ deep approaches to using online learning technologies. Instructor support was negatively related to students’ surface approaches to using online learning technologies.ConclusionsThe relationship between instructor role (instructor support, instructor-student interaction and instructor innovation) and students’ approaches to using online learning technologies highlight the importance of instructor support and innovation in facilitating students’ adoption of desirable approaches to learning from the application of technologies.
“Lost trust in the system”: system barriers to publicly available mental health and substance use services for transgender women in San Francisco
Authors: Baguso Glenda N. , Aguilar Karen , Sicro Sofia , Mañacop Malaya , Quintana Jerry , Wilson Erin C. 
Published: July 2022

Abstract
Background
Little is known about the barriers to mental health and substance use services for trans women living with HIV. We conducted a qualitative study with trans women living with HIV and providers to explore barriers to mental health and substance use services in San Francisco.

Methods
We conducted focus group discussions and key informant interviews with a total of 15 medical, mental health, substance use, and social service providers and trans women living with HIV. We identified, analyzed, and reported themes using thematic analysis and derived themes directly from the data.

Results
Our study participants identified two main themes and three subthemes. One main theme is that trans women and providers have lost trust in the system due to (a) lack of a linkage system between referrals and services, (b) structural barriers such as service location, language capacity, clinic hours, and (c) constant changes in services available. Another main theme is anti-trans and mental health stigma.

Conclusions
Interventions to coordinate linkage from medical to mental health and substance use (MHSU) services are urgently needed to facilitate the utilization of MHSU services. Other interventions to improve quality monitoring and system improvement, and to address multiple stigmas broadly in society are needed to improve unmet MHSU service needs among trans women living with HIV in San Francisco.
Applying the RE-AIM framework to evaluate a holistic caregiver-centric hospital-to-home programme: a feasibility study on Carer Matters
Authors: Chan Ee Yuee , Wu Ling Ting , Ng Emmalene Joo Yong , Glass George Frederick , Tan Robyn Hwee Teng 
Published: July 2022

Abstract
Background
Prolonged caregiving of an older adult can cause family caregivers to be overwhelmed, potentially affecting the well-being of both the caregivers and their care-recipients. Carer Matters is a holistic hospital-to-home programme, centred on caregivers’ needs as their care-recipients transit from hospital to home. The programme was piloted to support caregivers through caregivers needs assessment, tailored resources, tele-support, training courses, and community support network. This study aimed to examine the feasibility of Carer Matters in a tertiary hospital in Singapore.

Methods
This feasibility study was conducted on the pilot implementation from January to December 2021, during the Covid-19 pandemic. It adopted the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. The study highlighted quantitative data collected from key process indicators, such as number of caregivers screened, assessed on their needs and provided with assistance. Additionally, qualitative data was collected from in-depth interviews with 51 stakeholders involved in the implementation to examine their perspectives and experiences. These included family caregivers, clinician caregiver support nurses, hospital leaders and community partners.

Results
During the pilot, 550 caregivers were enrolled. All caregivers received educational resources when they completed the needs assessment, while 69 of them who reported high burden were given tele-support and 252 attended our caregiver training courses. Despite initial recruitment challenges and obstacles to adoption, stakeholders interviewed found Carer Matters to be effective in providing caregivers with emotional support, knowledge and skills that improved their caregiving abilities, and reduced their sense of isolation and caregiving stress. Among caregivers, the training courses were effective with majority of caregivers agreeing that the courses addressed their needs (99%) and improved their knowledge of the relevant disease conditions (97%). Programme maintenance considered among stakeholders included strategies such as multipronged approach in recruiting caregivers and inviting caregiver advocates to share their experiences.

Conclusion
This feasibility study highlights that Carer Matters is a valuable component to the ecosystem of support for family caregivers and their care recipients. Carer Matters extends the current patient-centric care model to a more holistic post-discharge continuity of care for both caregivers and their care-recipients, improving and maintaining their overall well-being to better allow transition from hospital-to home.

Trial registration
Feasibility Study of Project Carer Matters for Family Caregivers of Persons with Dementia (NCT number: NCT05205135).
Depleting TMED3 alleviates the development of endometrial carcinoma
Authors: Zhang Jin , Qi Yue 
Published: July 2022

AbstractBackgroundAs one of gynecologic tumors, endometrial carcinoma (EC) has been characterized by high incidence rate, but its molecular pathogenesis has remained unclear. TMED3 is a membrane protein and has been indicated to implicate several tumor-related diseases. In the current study, we aimed to explore the physiological function of TMED3 in EC progression.MethodsThrough bioinformatic analysis using The Cancer Genome Atlas database and immunohistochemistry assay on tissue microarray, we examined whether TMED3 was upregulated in EC tissues. After constructing TMED3-knockdown cell models via lentiviral transfection, qPCR and western blot were employed to determine the expression levels of TMED3 mRNA and protein. Then, Celigo cell counting assay, CCK8 assay, flow cytometry, wound-healing assay and Transwell assay were used to detect cell proliferation, cell cycle, cell apoptosis and cell migration, respectively.ResultsAs a result, it was found that TMED3 was upregulated in EC cells, which was also verified in clinical samples. We then found that downregulation of TMED3 considerably restrained cell cycle, cell growth and migration but promoted apoptosis of EC cells. The followingin-vivoexperiments also verified that tumor growth was inhibited after TMED3 knockdown. The exploration in molecular mechanisms showed that TMED3 deletion may weaken cellular viability through upregulating pro-apoptotic proteins and targeting PI3K/AKT signaling pathways.ConclusionsThis study suggested that knocking down TMED3 affected the malignant phenotype of EC cells and thus limited tumor progression, which provided insights to the development of targeted drugs for EC treatment.
Exploring views on medical care for people with intellectual disabilities: an international concept mapping study
Authors: Breuer Marian E. J. , Bakker-van Gijssel Esther J. , Vlot-van Anrooij Kristel , Tobi Hilde , Leusink Geraline L. , Naaldenberg Jenneken 
Published: July 2022

Abstract
Background
Medical care for people with intellectual and developmental disabilities (IDD) is organized differently across the globe and interpretation of the concept of medical care for people with IDD may vary across countries. Existing models of medical care are not tailored to the specific medical care needs of people with IDD. This study aims to provide an improved understanding of which aspects constitute medical care for people with IDD by exploring how international researchers and practitioners describe this care, using concept mapping.

Methods
Twenty-five experts (researchers and practitioners) on medical care for people with IDD from 17 countries submitted statements on medical care in their country in a brainstorming session, using an online concept mapping tool. Next, they sorted all collected statements and rated them on importance.

Results
Participants generated statements that reflect current medical and health care practice, their ideas on good practice, and aspirations for future medical and health care for people with IDD. Based on the sorting of all statements, a concept map was formed, covering 13 aspects that characterize medical and health care for people with IDD across nations. The 13 aspects varied minimally in importance ratings and were grouped into five overarching conceptual themes: (i) active patient role, (ii) provider role, (iii) context of care, (iv) consequences of care for people with IDD, and (v) quality of care.

Conclusions
The themes, clusters and statements identified through this explorative study provide additional content and context for the specific patient group of people with IDD to the dimensions of previous models of medical care.
Responding to a surge in overdose deaths: perspectives from US syringe services programs
Authors: Frost Madeline C. , Austin Elizabeth J. , Corcorran Maria A. , Briggs Elsa S. , Behrends Czarina N. , Juarez Alexa M. , Frank Noah D. , Healy Elise , Prohaska Stephanie M. , LaKosky Paul A. , Kapadia Shashi N. , Perlman David C. , Schackman Bruce R. , Des Jarlais Don C. , Williams Emily C. , Glick Sara N. 
Published: July 2022

Abstract
Background
US overdose deaths have reached a record high. Syringe services programs (SSPs) play a critical role in addressing this crisis by providing multiple services to people who use drugs (PWUD) that help prevent overdose death. This study examined the perspectives of leadership and staff from a geographically diverse sample of US SSPs on factors contributing to the overdose surge, their organization’s response, and ongoing barriers to preventing overdose death.

Methods
From 2/11/2021 to 4/23/2021, we conducted semi-structured interviews with leadership and staff from 27 SSPs sampled from the North American Syringe Exchange Network directory. Interviews were transcribed and qualitatively analyzed using a Rapid Assessment Process.

Results
Respondents reported that increased intentional and unintentional fentanyl use (both alone and combined with other substances) was a major driver of the overdose surge. They also described how the COVID-19 pandemic increased solitary drug use and led to abrupt increases in use due to life disruptions and worsened mental health among PWUD. In response to this surge, SSPs have increased naloxone distribution, including providing more doses per person and expanding distribution to people using non-opioid drugs. They are also adapting overdose prevention education to increase awareness of fentanyl risks, including for people using non-opioid drugs. Some are distributing fentanyl test strips, though a few respondents expressed doubts about strips’ effectiveness in reducing overdose harms. Some SSPs are expanding education and naloxone training/distribution in the broader community, beyond PWUD and their friends/family. Respondents described several ongoing barriers to preventing overdose death, including not reaching certain groups at risk of overdose (PWUD who do not inject, PWUD experiencing homelessness, and PWUD of color), an inconsistent naloxone supply and lack of access to intranasal naloxone in particular, inadequate funding, underestimates of overdoses, legal/policy barriers, and community stigma.

Conclusions
SSPs remain essential in preventing overdose deaths amid record numbers likely driven by increased fentanyl use and COVID-19-related impacts. These findings can inform efforts to support SSPs in this work. In the face of ongoing barriers, support for SSPs—including increased resources, political support, and community partnership—is urgently needed to address the worsening overdose crisis.