bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic umbrella review of the association of prescription drug insurance and cost-sharing with drug use, health services use, and health
Authors: Guindon G. Emmanuel , Fatima Tooba , Garasia Sophiya , Khoee Kimia 
Published: March 2022

Abstract
Background
Increasing spending and use of prescription drugs pose an important challenge to governments that seek to expand health insurance coverage to improve population health while controlling public expenditures. Patient cost-sharing such as deductibles and coinsurance is widely used with aim to control healthcare expenditures without adversely affecting health.

Methods
We conducted a systematic umbrella review with a quality assessment of included studies to examine the association of prescription drug insurance and cost-sharing with drug use, health services use, and health. We searched five electronic bibliographic databases, hand-searched eight specialty journals and two working paper repositories, and examined references of relevant reviews. At least two reviewers independently screened the articles, extracted the characteristics, methods, and main results, and assessed the quality of each included study.

Results
We identified 38 reviews. We found consistent evidence that having drug insurance and lower cost-sharing among the insured were associated with increased drug use while the lack or loss of drug insurance and higher drug cost-sharing were associated with decreased drug use. We also found consistent evidence that the poor, the chronically ill, seniors and children were similarly responsive to changes in insurance and cost-sharing. We found that drug insurance and lower drug cost-sharing were associated with lower healthcare services utilization including emergency room visits, hospitalizations, and outpatient visits. We did not find consistent evidence of an association between drug insurance or cost-sharing and health. Lastly, we did not find any evidence that the association between drug insurance or cost-sharing and drug use, health services use or health differed by socioeconomic status, health status, age or sex.

Conclusions
Given that the poor or near-poor often report substantially lower drug insurance coverage, universal pharmacare would likely increase drug use among lower-income populations relative to higher-income populations. On net, it is probable that health services use could decrease with universal pharmacare among those who gain drug insurance. Such cross-price effects of extending drug coverage should be included in costing simulations.
Prevalence and health correlates of workplace violence and discrimination against hospital employees – a cross-sectional study in German-speaking Switzerland
Authors: Stahl-Gugger Alenka , Hämmig Oliver 
Published: March 2022

Abstract
Background
Violence and discrimination are common events at work, especially in health care. Moreover, such workplace experiences are considered to have negative impacts and particularly adverse health consequences on health care workers. Nevertheless, the problem is still highly underreported and thus largely ignored and unexplored in Switzerland as comprehensive data and studies on their prevalence and health correlates among hospital staffs and health professionals are widely missing.

Methods
This cross-sectional study was based on secondary data from a company survey among several public hospitals and rehabilitation clinics in German-speaking Switzerland conducted in 2015/16. The study population was limited to a subsample of 1567 health professionals among the surveyed staffs of five participating hospitals and clinics. Relative frequencies of different forms of violence and discrimination at work and the total number of such experiences were calculated for the entire study population and for occupational subgroups. These data were compared with a nationally representative subsample of the Swiss Health Survey 2017 as a reference population. Multiple logistic regression analyses were further computed to investigate the association between the number of different experienced forms of violence and/or discrimination at work and several poor general and mental health outcomes.

Results
23% of the inverviewed hospital employees experienced at least one form of discrimination or violence at work in the past year, compared to 18% of the general working population. Nurses were by far the most affected occupational group regarding all forms of violence. More and particularly the most exposed and affected hospital employees with regard to experiences of violence and/or discrimination at work showed almost consistently increased frequencies and relative risks for the studied poor mental and general health outcomes. Prevalence rates and odds ratios for strong sleep disorders, strong stress feelings and increased burnout symptoms were between 3 and 4 times higher among the most exposed compared to the non-exposed group of hospital employees.

Conclusions
Study findings underline the importance of an active combat against violent and discriminatory behaviors in health care. Prevention strategies should particularly focus on nurses and midwives, which turned out to be the most affected and exposed group of all health professions.
Implementing the WHO Safe Childbirth Checklist modified for preterm birth: lessons learned and experiences from Kenya and Uganda
Authors: Achola Kevin Abidha , Kajjo Darious , Santos Nicole , Butrick Elizabeth , Otare Christopher , Mubiri Paul , Namazzi Gertrude , Merai Rikita , Otieno Phelgona , Waiswa Peter , Walker Dilys 
Published: March 2022

Abstract
Background
The WHO Safe Childbirth Checklist (SCC) contains 29 evidence-based practices (EBPs) across four pause points spanning admission to discharge. It has been shown to increase EBP uptake and has been tailored to specific contexts. However, little research has been conducted in East Africa on use of the SCC to improve intrapartum care, particularly for preterm birth despite its burden. We describe checklist adaptation, user acceptability, implementation and lessons learned.

Methods
The East Africa Preterm Birth Initiative (PTBi EA) modified the SCC for use in 23 facilities in Western Kenya and Eastern Uganda as part of a cluster randomized controlled trial evaluating a package of facility-based interventions to improve preterm birth outcomes. The modified SCC (mSCC) for prematurity included: addition of a triage pause point before admission; focus on gestational age assessment, identification and management of preterm labour; and alignment with national guidelines. Following introduction, implementation lasted 24 and 34 months in Uganda and Kenya respectively and was supported through complementary mentoring and data strengthening at all sites. PRONTO® simulation training and quality improvement (QI) activities further supported mSCC use at intervention facilities only. A mixed methods approach, including checklist monitoring, provider surveys and in-depth interviews, was used in this analysis.

Results
A total of 19,443 and 2229 checklists were assessed in Kenya and Uganda, respectively. In both countries, triage and admission pause points had the highest rates of completion. Kenya’s completion was greater than 70% for all pause points; Uganda ranged from 39 to 75%. Intervention facilities exposed to PRONTO and QI had higher completion rates than control sites. Provider perceptions cited clinical utility of the checklist, particularly when integrated into patient charts. However, some felt it repeated information in other documentation tools. Completion was hindered by workload and staffing issues.

Conclusion
This study highlights the feasibility and importance of adaptation, iterative modification and complementary activities to reinforce SCC use. There are important opportunities to improve its clinical utility by the addition of prompts specific to the needs of different contexts. The trial assessing the PTBi EA intervention package was registered at ClinicalTrials.gov NCT03112018 Registered December 2016, retrospectively registered.
Blood-feeding patterns of Anopheles vectors of human malaria in Malawi: implications for malaria transmission and effectiveness of LLIN interventions
Authors: Mbewe Rex B. , Keven John B. , Mzilahowa Themba , Mathanga Don , Wilson Mark , Cohee Lauren , Laufer Miriam K. , Walker Edward D. 
Published: March 2022

Abstract
Background
Access to human hosts by Anopheles mosquitoes is a key determinant of vectorial capacity for malaria, but it can be limited by use of long-lasting insecticidal nets (LLINs). In Malawi, pyrethroid-treated LLINs with and without the synergist piperonyl butoxide (PBO) were distributed to control malaria. This study investigated the blood-feeding patterns of malaria vectors and whether LLINs containing pyrethroid and PBO led to a reduction of human blood feeding than those containing only pyrethroids.

Methods
Mosquitoes were sampled inside houses from May 2019 through April 2020 by aspiration, pyrethrum spray catch, and light trap methods in two sites. One site (Namanolo, Balaka district) had LLINs containing only pyrethroids whereas the other (Ntaja, Machinga district) had LLINs with both pyrethroids and PBO. Anopheles species, their blood-meal host, and infection with Plasmodium falciparum were determined using PCR methods.

Results
A total of 6585 female Anopheles were sampled in 203 houses. Of these, 633 (9.6%) were blood-fed mosquitoes comprising of 279 (44.1%) Anopheles arabiensis, 103 (16.3%) Anopheles gambiae 212 (33.5), Anopheles funestus, 2 (0.3%), Anopheles parensis and 37 (5.8%) were unidentified Anopheles spp. Blood meal hosts were successfully identified for 85.5% (n = 541) of the blood-fed mosquitoes, of which 436 (81.0%) were human blood meals, 28 (5.2%) were goats, 11 (2.0%) were dogs, 60 (11.1%) were mixed goat-human blood meals, 5 (0.9%) were dog–human, and 1 was a mixed dog-goat. Human blood index (fraction of blood meals that were humans) was significantly higher in Namanolo (0.96) than Ntaja (0.89). Even though human blood index was high, goats were over-selected than humans after accounting for relative abundance of both hosts. The number of infectious Anopheles bites per person-year was 44 in Namanolo and 22 in Ntaja.

Conclusion
Although LLINs with PBO PBO may have reduced human blood feeding, access to humans was extremely high despite high LLIN ownership and usage rates in both sites. This finding could explain persistently high rates of malaria infections in Malawi. However, this study had one village for each net type, thus the observed differences may have been a result of other factors present in each village.
A global cautionary tale: discrimination and violence against trans women worsen despite investments in public resources and improvements in health insurance access and utilization of health care
Authors: Arayasirikul Sean , Turner Caitlin , Trujillo Dillon , Sicro Sofia L. , Scheer Susan , McFarland Willi , Wilson Erin C. 
Published: March 2022

Abstract
Background
To determine if improvements in social determinants of health for trans women and decreases in transphobic discrimination and violence occurred over three study periods during which extensive local programs were implemented to specifically address longstanding inequities suffered by the transgender community.

Methods
Interviewer-administered surveys from repeated cross-sectional Transwomen Empowered to Advance Community Health (TEACH) studies in 2010, 2013 and 2016-2017 in San Francisco collected experiences with transphobia violence and discrimination. Respondent-driven sampling was used to obtain a sample of participants who identified as a trans woman.

Results
Violence due to gender identity was prevalent; in each study period, verbal abuse or harassment was reported by over 83% of participants, and physical abuse or harassment was reported by over 56%. Adverse social determinants of health including homelessness, living below the poverty limit, methamphetamine use, depression, PTSD, and anxiety all significantly increased from 2010 to 2016. When testing for trends, housing discrimination and physical violence were both more likely in 2016-2017 compared to the two earlier study periods. Housing discrimination (aOR 1.41, 95% CI 1.00-1.98) and physical violence due to gender identity/presentation (aOR 1.39, 95% CI 1.00-1.92) both significantly increased from 2010 to 2016.

Conclusion
Our findings are particularly alarming during a period when significant public health resources and community-based initiatives specifically for trans women were implemented and could have reasonably led us to expect improvements. Despite these efforts, physical violence and housing discrimination among trans women worsened during the study periods. To ensure future improvements, research and interventions need to shift the focus and burden from trans people to cisgender people who are the perpetuators of anti-trans sentiment, stigma, discrimination and victimization.
Coenzyme Q10 supplementation improves adipokine profile in dyslipidemic individuals: a randomized controlled trial
Authors: Zhang Peiwen , Chen Ke , He Taiping , Guo Honghui , Chen Xu 
Published: March 2022

Abstract
Background
In previous study, we found that coenzyme Q10 (CoQ10) improved glucolipid profile in dyslipidemic individuals, but the mechanism is not yet clear. Adipokines have been demonstrated to be vital targets of metabolic diseases. The hypothesis that adipokines mediate the association of CoQ10 on glucolipid metabolism needs to be further studied in human.

Methods
In this randomized, double-blinded, placebo-controlled trial, 101 dyslipidemic individuals were administrated to 120 mg CoQ10 or placebo for 24 weeks. Anthropometric parameters, glucolipid profile, serum total adiponectin, leptin, and resistin were evaluated at baseline, week 12 and week 24.

Results
CoQ10 treatment significantly increased serum adiponectin levels at week 12 (165 [0, 362] ng/mL, p < 0.001) and at week 24 (523 [0, 1056] ng/mL, p < 0.001]), which was significant different compared with placebo (p < 0.001). The increase of adiponectin was negative associated with decrease in index of homeostasis model assessment of insulin resistance (HOMA-IR, r = − 0.465, p = 0.001), triglyceride (TG, r = − 0.297, p = 0.047), and low-density lipoprotein cholesterol (LDL-c, r = − 0.440, p = 0.002) at week 24 only in CoQ10-treated group. Resistin was reduced by CoQ10 only at week 24 (− 1.19 [− 4.35, 0.00] ng/mL, p < 0.001), which was significant different compared with placebo (p < 0.001). Reduction of resistin was positively correlated with the change in HOMA-IR (r = 0.343, p = 0.021) and TG (r = 0.323, p = 0.030) at week 24 in CoQ10-treated group but not placebo group. Leptin was not influenced by CoQ10 treatment. Mediation analysis indicated that the improvement of HOMA-IR, TG and LDL-c by CoQ10 was mediated by adiponectin but not resistin.

Conclusions
Our study shows that CoQ10 ameliorates glucolipid profile and adipokines dysfunction in dyslipidemic patients in 24 weeks’ intervention. The beneficial effect of CoQ10 on glucolipid profile was mediated by adiponectin. Trial registration: ClinicalTrials.gov, NCT02407548. Registered on April 3, 2015, https://clinicaltrials.gov/ct2/show/NCT02407548.
SATB2-associated syndrome: characterization of skeletal features and of bone fragility in a prospective cohort of 19 patients
Authors: Mouillé M. , Rio M. , Breton S. , Piketty M. L. , Afenjar A. , Amiel J. , Capri Y. , Goldenberg A. , Francannet C. , Michot C. , Mignot C. , Perrin L. , Quelin C. , Van Gils J. , Barcia G. , Pingault V. , Maruani G. , Koumakis E. , Cormier-Daire V. 
Published: March 2022

Abstract
Background
Individuals with pathogenic variants in SATB2 display intellectual disability, speech and behavioral disorders, dental abnormalities and often features of Pierre Robin sequence. SATB2 encodes a transcription factor thought to play a role in bone remodeling. The primary aim of our study was to systematically review the skeletal manifestations of SATB2-associated syndrome. For this purpose, we performed a non-interventional, multicenter cohort study, from 2017 to 2018. We included 19 patients, 9 females and 10 males ranging in age from 2 to 19 years-old. The following data were collected prospectively for each patient: clinical data, bone markers and calcium and phosphate metabolism parameters, skeletal X-rays and bone mineral density.

Results
Digitiform impressions were present in 8/14 patients (57%). Vertebral compression fractures affected 6/17 patients (35%). Skeletal demineralization (16/17, 94%) and cortical thinning of vertebrae (15/17) were the most frequent radiological features at the spine. Long bones were generally demineralized (18/19). The distal phalanges were short, thick and abnormally shaped. C-telopeptide (CTX) and Alkaline phosphatase levels were in the upper normal values and osteocalcin and serum procollagen type 1 amino-terminal propeptide (P1NP) were both increased. Vitamin D insufficiency was frequent (66.7%).

Conclusion
We conclude that SATB2 pathogenic variants are responsible for skeletal demineralization and osteoporosis. We found increased levels of bone formation markers, supporting the key role of SATB2 in osteoblast differentiation. These results support the need for bone evaluation in children and adult patients with SATB2-associated syndrome (SAS).
Advances in the diagnosis and treatment of sickle cell disease
Authors: Brandow A. M. , Liem R. I. 
Published: March 2022

AbstractSickle cell disease (SCD), which affects approximately 100,000 individuals in the USA and more than 3 million worldwide, is caused by mutations in the βb globin gene that result in sickle hemoglobin production. Sickle hemoglobin polymerization leads to red blood cell sickling, chronic hemolysis and vaso-occlusion. Acute and chronic pain as well as end-organ damage occur throughout the lifespan of individuals living with SCD resulting in significant disease morbidity and a median life expectancy of 43 years in the USA. In this review, we discuss advances in the diagnosis and management of four major complications: acute and chronic pain, cardiopulmonary disease, central nervous system disease and kidney disease. We also discuss advances in disease-modifying and curative therapeutic options for SCD. The recent availability ofl-glutamine, crizanlizumab and voxelotor provides an alternative or supplement to hydroxyurea, which remains the mainstay for disease-modifying therapy. Five-year event-free and overall survival rates remain high for individuals with SCD undergoing allogeneic hematopoietic stem cell transplant using matched sibling donors. However, newer approaches to graft-versus-host (GVHD) prophylaxis and the incorporation of post-transplant cyclophosphamide have improved engraftment rates, reduced GVHD and have allowed for alternative donors for individuals without an HLA-matched sibling. Despite progress in the field, additional longitudinal studies, clinical trials as well as dissemination and implementation studies are needed to optimize outcomes in SCD.
FAM167A is a key molecule to induce BCR-ABL-independent TKI resistance in CML via noncanonical NF-κB signaling activation
Authors: Yang Taewoo , Sim Kyu-Young , Ko Gwang-Hoon , Ahn Jae-Sook , Kim Hyeoung-Joon , Park Sung-Gyoo 
Published: March 2022

Abstract
Background
BCR-ABL-independent drug resistance is a barrier to curative treatment of chronic myeloid leukemia (CML). However, the molecular pathways underlying BCR-ABL-independent tyrosine kinase inhibitor (TKI) resistance remain unclear.

Methods
In silico bioinformatic analysis was performed to identify the most active transcription factor and its inducer that contribute to BCR-ABL-independent TKI resistance. Tandem mass spectrometry analysis was performed to identify the receptor for the noncanonical NF-κB activator FAM167A. In vitro and in vivo mouse experiments revealed detailed molecular insights into the functional role of the FAM167A-desmoglein-1 (DSG1) axis in BCL-ABL-independent TKI resistance. CML cells derived from CML patients were analyzed using quantitative reverse transcription PCR and flow cytometry.

Results
We found that NF-κB had the greatest effect on differential gene expression of BCR-ABL-independent TKI-resistant CML cells. Moreover, we found that the previously uncharacterized protein FAM167A activates the noncanonical NF-κB pathway and induces BCR-ABL-independent TKI resistance. Molecular analyses revealed that FAM167A activates the noncanonical NF-κB pathway by binding to the cell adhesion protein DSG1 to upregulate NF-κB-inducing kinase (NIK) by blocking its ubiquitination. Neutralization of FAM167A in a mouse tumor model reduced noncanonical NF-κB activity and restored sensitivity of cells to TKIs. Furthermore, FAM167A and surface DSG1 levels were highly upregulated in CD34+ CML cells from patients with BCR-ABL-independent TKI-resistant disease.

Conclusions
These results reveal that FAM167A acts as an essential factor for BCR-ABL-independent TKI resistance in CML by activating the noncanonical NF-κB pathway. In addition, FAM167A may serve as an important target and biomarker for BCR-ABL-independent TKI resistance.
Tumor bud-derived CCL5 recruits fibroblasts and promotes colorectal cancer progression via CCR5-SLC25A24 signaling
Authors: Gao Ling-Fang , Zhong Yan , Long Ting , Wang Xia , Zhu Jia-Xian , Wang Xiao-Yan , Hu Zhi-Yan , Li Zu-Guo 
Published: March 2022

Abstract
Background
Tumor budding is included in the routine diagnosis of colorectal cancer (CRC) and is considered a tumor prognostic factor independent of TNM staging. This study aimed to identify the fibroblast-mediated effect of tumor bud-derived C–C chemokine ligand 5 (CCL5) on the tumor microenvironment (TME).

Methods
Recruitment assays and a human cytokine array were used to detect the main cytokines that CRC tumor buds secrete to recruit fibroblasts. siRNA transfection and inhibitor treatment were used to investigate the role of fibroblast CCL5 receptors in fibroblast recruitment. Subsequently, transcriptome sequencing was performed to explore the molecular changes occurring in fibroblasts upon stimulation with CCL5. Finally, clinical specimens and orthotopic xenograft mouse models were studied to explore the contribution of CCL5 to angiogenesis and collagen synthesis.

Results
Hematoxylin–eosin staining and immunochemistry revealed a higher number of fibroblasts at the invasive front of CRC tissue showing tumor budding than at sites without tumor budding. In vitro experiments demonstrated that CCL5 derived from tumor buds could recruit fibroblasts by acting on the CCR5 receptors on fibroblasts. Tumor bud-derived CCL5 could also positively regulate solute carrier family 25 member 24 (SLC25A24) expression in fibroblasts, potentially activating pAkt-pmTOR signaling. Moreover, CCL5 could increase the number of α-SMAhigh CD90high FAPlow fibroblasts and thus promote tumor angiogenesis by enhancing VEGFA expression and making fibroblasts transdifferentiate into vascular endothelial cells. Finally, the results also showed that CCL5 could promote collagen synthesis through fibroblasts, thus contributing to tumor progression.

Conclusions
At the invasive front of CRC, tumor bud-derived CCL5 can recruit fibroblasts via CCR5-SLC25A24 signaling, further promoting angiogenesis and collagen synthesis via recruited fibroblasts, and eventually create a tumor-promoting microenvironment. Therefore, CCL5 may serve as a potential diagnostic marker and therapeutic target for tumor budding in CRC.