bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring barriers and facilitators to PrEP use among transgender women in two urban areas: implications for messaging and communication
Authors: Bass Sarah Bauerle , Kelly Patrick J. , Brajuha Jesse , Gutierrez-Mock Luis , Koester Kimberly , D’Avanzo Paul , Sevelius Jae
Published: January 2022

Background

Trans women are at increased risk for HIV infection yet are less likely to use pre-exposure prophylaxis (PrEP) medication as a preventive measure. PrEP messaging and marketing has focused on men who have sex with men (MSM) or included trans women as a subset of MSM, ignoring the potential barriers to PrEP use unique to trans women. Little is known about how this group conceptualizes PrEP, what knowledge gaps still exist, and how trans women believe PrEP should be communicated to increase use.

Methods

This qualitative study conducted focus groups (n = 5) in Philadelphia and Sacramento with trans women to assess these issues.

Results

Twelve sub-themes were found related to five main domains, including PrEP knowledge, benefits, barriers, community-related considerations, and messaging/marketing. Findings indicate that knowledge of PrEP is still low and beliefs about PrEP’s effects on hormone use persist. Most importantly, participants voiced a demand for culturally appropriate trans-specific messages in HIV prevention interventions and communication.

Conclusions

Without acknowledging specific barriers to PrEP uptake among transgender women separate from those of MSM and incorporating gender affirmation into PrEP education, simply knowing PrEP is available may not motivate trans women to use PrEP. This has important implications for future efforts to communicate about PrEP with trans women.
Developing and implementing a new methodology to test the affordability of currently popular weight loss diet meal plans and healthy eating principles
Authors: Bracci Ella L. , Milte Rachel , Keogh Jennifer B. , Murphy Karen J.
Published: January 2022

Background

Weight loss diets continue to rise in popularity; however, the associated costs are seldom reported. Certain weight loss diets may be unaffordable and differ from their traditional nutrition composition to include non-conventional premium products. In contrast, healthy eating principles such as the Australian Guide to Healthy Eating (AGHE) and the Mediterranean Diet (MedDiet) place an emphasis on fresh produce and staple foods but are sometimes thought to be unaffordable. A new methodology was piloted to assess the cost of weight loss diets using seven meal plans.

Methods

Seven meal plans were analysed to quantify the absolute grams required of all ingredients across seven days and multiplied by the cost of the ingredient per gram to determine the total cost of each ingredient based on unit size and price. The weekly grocery shopping cost was determined through summation of all ingredients and their entire unit size to compare weekly costs.

Results

Weekly meal plans (absolute grams) cost between $93-193AUD. The AGHE meal plan was the least expensive and 8 Weeks to Wow was the most expensive. Weekly grocery shopping of entire units cost between $345-$625AUD, over $100AUD greater than the spending of an average Australian ($237AUD/week).

Conclusions

The financial feasibility for long-term sustainment of weight loss diets may be questionable for groups including low-income earners and low socioeconomic status. Further, when dietary patterns are adapted for weight loss, or followed by consumers, deviations from foundational principles tend to occur which may influence overall cost.
Association of perceived work pace and physical work demands with occupational accidents: a cross-sectional study of ageing male construction workers in Denmark
Authors: Hansen Pernille Weber , Schlünssen Vivi , Fonager Kirsten , Bønløkke Jakob Hjort , Hansen Claus D. , Bøggild Henrik
Published: January 2022

Background

Occupational accidents continue to be a significant public health challenge worldwide. Construction workers in particular are at high risk of occupational accidents, and thus it is of major importance to identify possible predictors of occupational accidents among construction workers. We aimed to investigate the association between self-reported work pace and physical work demands and occupational accidents among ageing male construction workers in Denmark.

Methods

Data on perceived work pace, physical work demands, and occupational accidents was acquired from questionnaires sent to ageing construction workers in Denmark in 2016 as part of the ALFA project (ALdring og Fysisk Arbejde; Ageing and Physical Work). A sample of 1270 Danish male construction workers above 50 years of age was included in the present study. Multiple logistic regression models were applied, with adjustments for age, smoking, body mass index, musculoskeletal disorders, occupation, work experience, and support at work.

Results

Of 1270 construction workers, 166 (13.1%) reported an occupational accident within the last 12 months. There was no significant association between perceived work pace and occupational accidents, but physical work demands were associated with higher odds for occupational accidents, with an odds ratio of 2.27 (95% confidence interval 1.26–4.10) for medium physical work demands and 2.62 (95% confidence interval 1.50–4.57) for high physical work demands.

Conclusions

Ageing male construction workers with high physical work demands had statistically significant higher odds of having an occupational accident. By contrast, perceived work pace was not associated with occupational accidents in this large cross-sectional study.
Tracheal stenosis in prolonged mechanically ventilated patients: prevalence, risk factors, and bronchoscopic management
Authors: Ghiani Alessandro , Tsitouras Konstantinos , Paderewska Joanna , Munker Dieter , Walcher Swenja , Neurohr Claus , Kneidinger Nikolaus
Published: January 2022

Background

Various complications may arise from prolonged mechanical ventilation, but the risk of tracheal stenosis occurring late after translaryngeal intubation or tracheostomy is less common. This study aimed to determine the prevalence, type, risk factors, and management of tracheal stenoses in mechanically ventilated tracheotomized patients deemed ready for decannulation following prolonged weaning.

Methods

A retrospective observational study on 357 prolonged mechanically ventilated, tracheotomized patients admitted to a specialized weaning center over seven years. Flexible bronchoscopy was used to discern the type, level, and severity of tracheal stenosis in each case. We described the management of these stenoses and used a binary logistic regression analysis to determine independent risk factors for stenosis development.

Results

On admission, 272 patients (76%) had percutaneous tracheostomies, and 114 patients (32%) presented mild to moderate tracheal stenosis following weaning completion, with a median tracheal cross-section reduction of 40% (IQR 25–50). The majority of stenoses (88%) were located in the upper tracheal region, most commonly resulting from localized granulation tissue formation at the site of the internal stoma (96%). The logistic regression analysis determined that obesity (OR 2.16 [95%CI 1.29–3.63], P < 0.01), presence of a percutaneous tracheostomy (2.02 [1.12–3.66], P = 0.020), and cricothyrotomy status (5.35 [1.96–14.6], P < 0.01) were independently related to stenoses. Interventional bronchoscopy with Nd:YAG photocoagulation was a highly effective first-line treatment, with only three patients (2.6%) ultimately referred to tracheal surgery.

Conclusions

Tracheal stenosis is commonly observed among prolonged ventilated patients with tracheostomies, characterized by localized hypergranulation and mild to moderate airway obstruction, with interventional bronchoscopy providing satisfactory results.
Treatment of chronic osteomyelitis with antibiotic-impregnated polymethyl methacrylate (PMMA) – the Cierny approach: is the second stage necessary?
Authors: Bor Noam , Dujovny Eytan , Rinat Barak , Rozen Nimrod , Rubin Guy
Published: January 2022

Background

Chronic osteomyelitis is a challenge for orthopedic surgeons. Most patients with osteomyelitis receive two-stage management according to Cierny-Mader. The first stage includes radical debridement and insertion of an antibiotic-impregnated cement spacer (ACS) (beads, rods, nails, or blocks) into the bone defect. The second stage is performed 6–8 weeks later, when the spacer is removed and a cancellous autograft is placed within the bone defect. The possibility of ACS as definitive management for osteomyelitis, avoiding the second stage, is presented.

Methods

Sixteen patients with osteomyelitis received radical debridement and insertion of an ACS in all forms into the bone defect as a definitive management. In 8 patients, the tibia was infected, 4 had femur infection, 2 humerus, 1 fibula, and 1 ankle. The mean age at the time of the first stage of reconstruction was 49 years (range, 13–71 years). According to the Cierny-Mader classification, 1 patient was C-M IA, another was IB, 7 IIIA, 6 IIIB, and 1 was 4A. All B hosts had systemic illnesses. The mean follow-up period was 6 years (1.5–16 years).

Results

No patient exhibited radiographic evidence of excessive bone loss. Signs of recurrence of osteomyelitis were not noted in any of the patients, and no fractures had occurred by the last follow-up.

Conclusion

Our study suggests that a proportion of patients with planned retention of ACS appear to function well without requiring further surgical intervention, especially in elderly or vulnerable patients.
Clinical and biological risk factors associated with inflammation in patients with type 2 diabetes mellitus
Authors: Ellulu Mohammed S. , Samouda Hanen
Published: January 2022

Background

Chronic inflammation has been associated with insulin resistance and related metabolic dysregulation, including type 2 diabetes mellitus (T2DM). Several non modifiable (i.e. genetic predisposition) and modifiable (i.e. sedentary lifestyle, energy-dense food) risk factors were suggested to explain the mechanisms involved in the development of inflammation, but are difficult to assess in clinical routine. The present study aimed to identify easy to asses clinical and biological risk factors associated with inflammation in patients with T2DM.

Methods

One hundred nine patients (51 men, 58 women), 28–60 years old, from seven primary healthcare centers in Gaza City, Palestine, took part to the cross-sectional study (November 2013–May 2014). Study participants had T2DM with no history of inflammatory diseases, cardiovascular diseases, medication and/or any health condition that might affect the inflammatory markers, interleukin 6 (IL-6) and C-reactive protein (CRP). Inflammation was defined for IL-6 ≥ 2 pg/mL and CRP ≥ 6 mg/L. Multivariable logistic regressions were used to identify the relationship between inflammation and clinical and biological risk factors.

Results

After adjustment for age and gender, inflammation seems to increase with increased body mass index (BMI) (OR: 1.427 [1.055–1.931]), increased fasting blood glucose (OR: 1.029 [1.007–1.052]) and decreased adiponectin values (OR: 0.571 [0.361–0.903]).

There were also significant relationships between inflammation and BMI (OR: 1.432 [1.042–1.968]), fasting blood glucose (OR: 1.029 [1.006–1.052]) and adiponectin (OR: 0.569 [0.359–0.902]), after adjustment for smoking habits and physical activity.

Conclusion

Managing obesity and associated complications (i.e. hyperglycemia, high adiponectin levels) might help decreasing inflammation in individuals with T2DM.
A focus on the future of opioid prescribing: implementation of a virtual opioid and pain management module for medical students
Authors: Adalbert Jenna R. , Ilyas Asif M.
Published: January 2022

Background

The United States opioid epidemic is a devastating public health crisis fueled in part by physician prescribing. While the next generation of prescribers is crucial to the trajectory of the epidemic, medical school curricula designated to prepare students for opioid prescribing (OP) and pain management is often underdeveloped. In response to this deficit, we aimed to investigate the impact of an online opioid and pain management (OPM) educational intervention on fourth-year medical student knowledge, attitudes, and perceived competence.

Methods

Graduating students completing their final year of medical education at Sidney Kimmel Medical College of Thomas Jefferson University were sent an e-mail invitation to complete a virtual OPM module. The module consisted of eight interactive patient cases that introduced topics through a case-based learning system, challenging students to make decisions and answer knowledge questions about the patient care process. An identical pre- and posttest were built into the module to measure general and case-specific learning objectives, with responses subsequently analyzed using the Wilcoxon matched-pairs signed-rank test.

Results

Forty-three students (19% response rate) completed the module. All median posttest responses ranked significantly higher than paired median pretest responses (p <  0.05). Comparing the paired overall student baseline score to module completion, median posttest ranks (Mdn = 206, IQR = 25) were significantly higher than median pretest ranks (Mdn = 150, IQR = 24) (p <  0.001). Regarding paired median Perceived Competence Scale metrics specifically, perceived student confidence, capability, and ability in opioid management increased from “disagree” (2) to “agree” (4) (p <  0.001), and student ability to meet the challenge of opioid management increased from “neither agree nor disagree” (3) to “agree” (4) (p <  0.001). Additionally, while 77% of students reported receiving OP training in medical school, 21% reported no history of prior training.

Conclusion

Implementation of a virtual, interactive module with clinical context is an effective framework for improving the OPM knowledge, attitudes, and perceived competence of fourth-year medical students. This type of intervention may be an important method for standardizing and augmenting the education of future prescribers across multiple institutions.
PrAna: an R package to calculate and visualize England NHS primary care prescribing data
Authors: Jagadeesan Kishore Kumar , Grant James , Griffin Sue , Barden Ruth , Kasprzyk-Hordern Barbara
Published: January 2022

Background

The objective of this work to calculate prescribed quantity of an active pharmaceutical ingredient (API) in prescription medications for human use, to facilitate research on the prediction of amount of API released to the environment and create an open-data tool to facilitate spatiotemporal and long-term prescription trends for wider usage.

Design

We have developed an R package, PrAna to calculate the prescribed quantity (in kg) of an APIs by postcode using England’s national level prescription data provided by National Health Service, for the years 2015–2018. Datasets generated using PrAna can be visualized in a real-time interactive web-based tool, PrAnaViz to explore spatiotemporal and long-term trends. The visualisations can be customised by selecting month, year, API, and region.

Results

PrAnaViz’s targeted API approach is demonstrated with the visualisation of prescribed quantities of 14 APIs in the Bath and North East Somerset (BANES) region during 2018. Once the APIs list is loaded, the back end retrieves relevant data and populates the graphs based on user-defined data features in real-time. These plots include the prescribed quantity of APIs over a year, by month, and individual API by month, general practice, postcode, and medicinal form. The non-targeted API approach is demonstrated with the visualisation of clarithromycin prescribed quantities at different postcodes in the BANES region.

Conclusion

PrAna and PrAnaViz enables the analysis of spatio-temporal and long-term trends with prescribed quantities of different APIs by postcode. This can be used as a support tool for policymakers, academics and researchers in public healthcare, and environmental scientist to monitor different group of pharmaceuticals emitted to the environment and for prospective risk assessment of pharmaceuticals in the environment.
Does de-implementation of low-value care impact the patient-clinician relationship? A mixed methods study
Authors: Rockwell Michelle S. , Michaels Kenan C. , Epling John W.
Published: January 2022

Background

The importance of reducing low-value care (LVC) is increasingly recognized, but the impact of de-implementation on the patient-clinician relationship is not well understood. This mixed-methods study explored the impact of LVC de-implementation on the patient-clinician relationship.

Methods

Adult primary care patients from a large Virginia health system volunteered to participate in a survey (n = 232) or interview (n= 24). Participants completed the Patient-Doctor Relationship Questionnaire (PDRQ-9) after reading a vignette about a clinician declining to provide a low-value service: antibiotics for acute sinusitis (LVC-antibiotics); screening EKG (LVC-EKG); screening vitamin D test (LVC-vitamin D); or an alternate vignette about a high-value service, and imagining that their own primary care clinician had acted in the same manner. A different sample of participants was asked to imagine that their own primary care clinician did not order LVC-antibiotics or LVC-EKG and then respond to semi-structured interview questions. Outcomes data included participant demographics, PDRQ-9 scores (higher score = greater relationship integrity), and content analysis of transcribed interviews. Differences in PDRQ-9 scores were analyzed using one-way ANOVA. Data were integrated for analysis and interpretation.

Results

Although participants generally agreed with the vignette narrative (not providing LVC), many demonstrated difficulty comprehending the broad concept of LVC and potential harms. The topic triggered memories of negative experiences with healthcare (typically poor-quality care, not necessarily LVC). The most common recommendation for reducing LVC was for patients to take greater responsibility for their own health. Most participants believed that their relationship with their clinician would not be negatively impacted by denial of LVC because they trusted their clinician’s guidance. Participants emphasized that trusted clinicians are those who listen to them, spend time with them, and offer understandable advice. Some felt that not providing LVC would actually increase their trust in their clinician. Similar PDRQ-9 scores were observed for LVC-antibiotics (38.9), LVC-EKG (37.5), and the alternate vignette (36.4), but LVC-vitamin D was associated with a significantly lower score (31.2) (p < 0.05).

Conclusions

In this vignette-based study, we observed minimal impact of LVC de-implementation on the patient-clinician relationship, although service-specific differences surfaced. Further situation-based research is needed to confirm study findings.
Molecular characterization and phylogenetic analysis of bovine ephemeral fever viruses in Khuzestan province of Iran in 2018 and 2020
Authors: Rezatofighi Seyedeh Elham , Mirzadeh Khalil , Mahmoodi Fahimeh
Published: January 2022

Background

Bovine ephemeral fever (BEF) is an arthropod-borne viral disease caused by the BEF virus (BEFV). This single-stranded RNA virus that affects cattle and water buffalo is endemic in tropical and subtropical regions including Iran. While BEF is a major disease of cattle in Iran, information regarding its agent, molecular characterization, and circulating viruses are highly limited. The current study aimed to, firstly, determine the genetic and antigenic characteristics of BEFV strains in Khuzestan province in Southwest of Iran in 2018 and 2020 and, secondly, to compare them with strains obtained from other areas.

Results

By phylogenetic analysis based on the Glycoprotein gene, BEFV strains were divided into four clusters of Middle East, East Asia, South Africa, and Australia; in which the 2018 and 2020 Iranian BEFV strains were grouped in the Middle East cluster with the Turkish, Indian, and Israeli strains. Depending on the chronology and geographical area, the outbreaks of Turkey (2020), Iran (2018 and 2020), and India (2018 and 2019) are proposed to be related. These BEFVs had the highest identity matrix and the lowest evolutionary distance among the studied strains. Multiple sequence alignment of G1, G2, and G3 antigenic sites showed that these neutralizing epitopes are highly conserved among the strains of the Middle East cluster; however, the strains previously identified in Iran differed in three amino acids placed in G1 and G2 epitopes.

Conclusion

The findings revealed that BEFVs circulating in the Middle East are closely related phylogenetically and geographically. They also have similar antigenic structures; therefore, developing a vaccine based on these strains can be effective for controlling BEF in the Middle East.
Effects of treatment with SGLT-2 inhibitors on arginine-related cardiovascular and renal biomarkers
Authors: Gessner Arne , Gemeinhardt Anna , Bosch Agnes , Kannenkeril Dennis , Staerk Christian , Mayr Andreas , Fromm Martin F. , Schmieder Roland E. , Maas Renke
Published: January 2022

Background

In patients with type 2 diabetes (T2D) sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve glycaemic control as well as cardiovascular and renal outcomes. Their effects onl-arginine (Arg) related risk markers asymmetric and symmetric dimethylarginine (ADMA and SDMA) and the protective biomarker L-homoarginine (hArg) linking T2D to cardiovascular and renal disease have not yet been reported.

Methods

Plasma and 24-h urine samples taken before and after 6 weeks of treatment were available from two prospective, randomized, double-blind, placebo-controlled, cross-over trials with empagliflozin (71 patients analyzed, NCT02471963) and dapagliflozin (59 patients analyzed, NCT02383238). In these samples, concentrations of hArg, Arg, ADMA, SDMA, and creatinine were determined by liquid-chromatography coupled to tandem mass-spectrometry. Additionally, intraindividual changes of the biomarkers in plasma were correlated with intraindividual changes of clinical parameters.

Results

Treatment with empagliflozin and dapagliflozin was associated with a reduction of plasma hArg by 17.5% and 13.7% (both p < 0.001), respectively, and increase in plasma SDMA concentration of 6.7% and 3.6%, respectively (p < 0.001 and p < 0.05), while plasma Arg and ADMA concentrations were not significantly altered. 24-h urinary excretion of ADMA was reduced by 15.2% after treatment with empagliflozin (p < 0.001) but not after dapagliflozin treatment, while excretion of the other markers was not significantly altered. Renal clearance of SDMA was reduced by 9.1% and 3.9% for both drugs (both p < 0.05). A reduction in ADMA clearance was observable after empagliflozin treatment only (− 15.5%, p < 0.001), but not after dapagliflozin. Renal clearance of hArg and Arg was not significantly altered. Treatment effects onl-arginine related biomarkers were not constantly correlated with effects on glycated hemoglobin, fasting plasma glucose, body mass index, and systolic blood pressure.

Conclusions

Treatment with SGLT-2 inhibitors has divergent effects on Arg-related biomarkers and could affect risk estimates associated with these markers. The observed effects are unlikely to explain the known cardiovascular and renal benefits of treatment with empagliflozin or dapagliflozin but still may indicate new therapeutic approaches in patients treated with SGLT-2 inhibitors.

Trial registrationhttp://www.clinicaltrials.gov: NCT02471963 (registered 15th June 2015, retrospectively registered) and NCT02383238.
PHD finger protein 20-like protein 1 (PHF20L1) in ovarian cancer: from its overexpression in tissue to its upregulation by the ascites microenvironment
Authors: Alberto-Aguilar Dulce Rosario , Hernández-Ramírez Verónica Ivonne , Osorio-Trujillo Juan Carlos , Gallardo-Rincón Dolores , Toledo-Leyva Alfredo , Talamás-Rohana Patricia
Published: January 2022

Background

Ovarian cancer is the most aggressive gynecological malignancy. Transcriptional regulators impact the tumor phenotype and, consequently, clinical progression and response to therapy. PHD finger protein 20-like protein 1 (PHF20L1) is a transcriptional regulator with several isoforms, and studies on its role in ovarian cancer are limited. We previously reported that PHF20L1 is expressed as a fucosylated protein in SKOV-3 cells stimulated with ascites from patients with ovarian cancer.

Methods

We decided to analyze the expression of PHF20L1 in ovarian cancer tissues, determine whether a correlation exists between PHF20L1 expression and patient clinical data, and analyze whether ascites can modulate the different isoforms of this protein. Ovarian cancer biopsies from 29 different patients were analyzed by immunohistochemistry, and the expression of the isoforms in ovarian cancer cells with or without exposure to the tumor microenvironment, i.e., the ascitic fluid, was determined by western blotting assays.

Results

Immunohistochemical results suggest that PHF20L1 exhibits increased expression in sections of tumor tissues from patients with ovarian cancer and that higher PHF20L1 expression correlates with shorter progression-free survival and shorter overall survival. Furthermore, western blotting assays determined that protein isoforms are differentially regulated in SKOV-3 cells in response to stimulation with ascites from patients with epithelial ovarian cancer.

Conclusion

The results suggest that PHF20L1 could play a relevant role in ovarian cancer given that higher PHF20L1 protein expression is associated with lower overall patient survival.
Annexin A1 promotes the progression of bladder cancer via regulating EGFR signaling pathway
Authors: Li Piao , Li Lingling , Li Zhou , Wang Shennan , Li Ruichao , Zhao Weiheng , Feng Yanqi , Huang Shanshan , Li Lu , Qiu Hong , Xia Shu
Published: January 2022

Background

Bladder cancer (BLCA) is one of the most common malignancies worldwide. One of the main reasons for the unsatisfactory management of BLCA is the complex molecular biological mechanism. Annexin A1 (ANXA1), a Ca2+-regulated phospholipid-binding protein, has been demonstrated to be implicated in the progression and prognosis of many cancers. However, the expression pattern, biological function and mechanism of ANXA1 in BLCA remain unclear.

Methods

The clinical relevance of ANXA1 in BLCA was investigated by bioinformatics analysis based on TCGA and GEO datasets. Immunohistochemical (IHC) analysis was performed to detect the expression of ANXA1 in BLCA tissues, and the relationships between ANXA1 and clinical parameters were analyzed. In vitro and in vivo experiments were conducted to study the biological functions of ANXA1 in BLCA. Finally, the potential mechanism of ANXA1 in BLCA was explored by bioinformatics analysis and verified by in vitro and in vivo experiments.

Results

Bioinformatics and IHC analyses indicated that a high expression level of ANXA1 was strongly associated with the progression and poor prognosis of patients with BLCA. Functional studies demonstrated that ANXA1 silencing inhibited the proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) of BLCA cells in vitro, and suppressed the growth of xenografted bladder tumors in vivo. Mechanistically, loss of ANXA1 decreased the expression and phosphorylation level of EGFR and the activation of downstream signaling pathways. In addition, knockdown of ANXA1 accelerated ubiquitination and degradation of P-EGFR to downregulate the activation of EGFR signaling.

Conclusions

These findings indicate that ANXA1 is a reliable clinical predictor for the prognosis of BLCA and promotes proliferation and migration by activating EGFR signaling in BLCA. Therefore, ANXA1 may be a promising biomarker for the prognosis of patients with BLCA, thus shedding light on precise and personalized therapy for BLCA in the future.
Systematic analysis of the role of SLC52A2 in multiple human cancers
Authors: Zhang Lilong , Li Man , Cui Zhoujun , Chai Dongqi , Guan Yongjun , Chen Chen , Wang Weixing
Published: January 2022

Background

In humans, riboflavin must be obtained through intestinal absorption because it cannot be synthesized by the body. SLC52A2 encodes a membrane protein belonging to the riboflavin transporter protein family and is associated with a variety of diseases. Here, we systematically explore its relevance to multiple human tumors.

Methods

We analyzed the association of SLC52A2 with 33 tumors using publicly available databases such as TCGA and GEO. We verified the SLC52A2 expression in hepatocellular carcinoma, gastric cancer, colon cancer, and rectal cancer using immunohistochemistry.

Results

We report that SLC52A2 was highly expressed in almost all tumors, and the immunohistochemical results in the hepatocellular, gastric, colon, and rectal cancers were consistent with the above. SLC52A2 expression was linked to patient overall survival, disease-specific survival, progression-free interval, diagnosis, mutations, tumor mutational burden, microsatellite instability, common immune checkpoint genes, and immune cells infiltration. Enrichment analysis showed that SLC52A2 was mainly enriched in oocyte meiosis, eukaryotic ribosome biogenesis, and cell cycle. In hepatocellular carcinoma, the SLC52A2 expression is an independent prognostic factor. The SNHG3 and THUMPD3-AS1/hsa-miR-139-5p-SLC52A2 axis were identified as potential regulatory pathways in hepatocellular carcinoma.

Conclusion

In conclusion, we have systematically described for the first time that SLC52A2 is closely associated with a variety of tumors, especially hepatocellular carcinoma.
Hydrogel composite scaffolds achieve recruitment and chondrogenesis in cartilage tissue engineering applications
Authors: Huang Bo , Li Pinxue , Chen Mingxue , Peng Liqing , Luo Xujiang , Tian Guangzhao , Wang Hao , Wu Liping , Tian Qinyu , Li Huo , Yang Yu , Jiang Shuangpeng , Yang Zhen , Zha Kangkang , Sui Xiang , Liu Shuyun , Guo Quanyi
Published: January 2022

Background

The regeneration and repair of articular cartilage remains a major challenge for clinicians and scientists due to the poor intrinsic healing of this tissue. Since cartilage injuries are often clinically irregular, tissue-engineered scaffolds that can be easily molded to fill cartilage defects of any shape that fit tightly into the host cartilage are needed.

Method

In this study, bone marrow mesenchymal stem cell (BMSC) affinity peptide sequence PFSSTKT (PFS)-modified chondrocyte extracellular matrix (ECM) particles combined with GelMA hydrogel were constructed.

Results

In vitro experiments showed that the pore size and porosity of the solid-supported composite scaffolds were appropriate and that the scaffolds provided a three-dimensional microenvironment supporting cell adhesion, proliferation and chondrogenic differentiation. In vitro experiments also showed that GelMA/ECM-PFS could regulate the migration of rabbit BMSCs. Two weeks after implantation in vivo, the GelMA/ECM-PFS functional scaffold system promoted the recruitment of endogenous mesenchymal stem cells from the defect site. GelMA/ECM-PFS achieved successful hyaline cartilage repair in rabbits in vivo, while the control treatment mostly resulted in fibrous tissue repair.

Conclusion

This combination of endogenous cell recruitment and chondrogenesis is an ideal strategy for repairing irregular cartilage defects.

Graphical Abstract
CRISPR/Cas9 delivery by NIR-responsive biomimetic nanoparticles for targeted HBV therapy
Authors: Wang Dan , Chen Ling , Li Chengbi , Long Quanxin , Yang Qing , Huang Ailong , Tang Hua
Published: January 2022

Background

Currently, there are no curative drugs for hepatitis B virus (HBV). Complete elimination of HBV covalently closed circular DNA (cccDNA) is key to the complete cure of hepatitis B virus infection. The CRISPR/Cas9 system can directly destroy HBV cccDNA. However, a CRISPR/Cas9 delivery system with low immunogenicity and high efficiency has not yet been established. Moreover, effective implementation of precise remote spatiotemporal operations in CRISPR/Cas9 is a major limitation.

Results

In this work, we designed NIR-responsive biomimetic nanoparticles (UCNPs-Cas9@CM), which could effectively deliver Cas9 RNP to achieve effective genome editing for HBV therapy. HBsAg, HBeAg, HBV pgRNA and HBV DNA along with cccDNA in HBV-infected cells were found to be inhibited. These findings were confirmed in HBV-Tg mice, which did not exhibit significant cytotoxicity and minimal off-target DNA damage.

Conclusions

The UCNPs-based biomimetic nanoplatforms achieved the inhibition of HBV replication via CRISPR therapy and it is a potential system for efficient treatment of human HBV diseases.

Graphical Abstract
Stress, pain, and work affiliation are strongly associated with health-related quality of life in parents of 14–15-year-old adolescents
Authors: Rohde Gudrun , Helseth Sølvi , Mikkelsen Hilde Timenes , Skarstein Siv , Småstuen Milada Cvancarova , Haraldstad Kristin
Published: January 2022

Background

For many adults, their role as a parent is a vital part of their lives. This role is likely to be associated with a parent’s health-related quality of life (HRQOL). The aim of this study was to explore the associations between gender, demographic and psychosocial variables, pain, and HRQOL in parents of 14–15-year-old adolescents.

Methods

This was a cross-sectional study that included 561 parents. Data on demographic, psychosocial variables and pain were collected using validated instruments. HRQOL was assessed using the RAND-36. Data were analysed using univariate and hierarchical multiple linear regression analyses.

Results

Four hundred and thirty-six (78%) mothers and 125 (22%) fathers with a mean age of 45 (SD = 5) years were included. Eighty-one per cent were married/cohabiting, 74% worked full time, and 50% had university education of more than 4 years. Almost one-third reported daily or weekly pain, and more than half (58%) reported using pain analgesics during the previous 4 weeks. Mothers reported significantly lower scores on self-efficacy, self-esteem and for all RAND-36 domains, including the physical component summary (PCS) and mental component summary (MCS) and experienced greater stress than fathers. Hierarchical regression analyses showed that working part-time (beta = 0.40) or full time (beta = 0.52) (reference: not working) had the strongest positive effect on PCS. Absence from work for > 10 days (beta = −0.24) (reference: no absence), short-term pain (beta = −0.14), chronic pain (beta = −0.37) (reference: no pain), and stress (beta = −0.10) had the strongest negative effects on PCS. High self-esteem (beta = 0.11) had the strongest positive effect, whereas stress (beta = −0.58) and absence from work for > 10 days (beta = −0.11) (reference: no absence) had the strongest negative effects on MCS.

Conclusion

Mothers reported significantly lower scores on self-efficacy, self-esteem, and HRQOL, and experienced greater stress than the fathers. A high proportion of parents reported pain. Pain, stress, and low work affiliation were strongly associated with decreased HRQOL in parents. We recommend that parents of adolescents should be provided guidance about coping with pain and stress, and facilitation of a strong work affiliation because these seem to be important to parents’ HRQOL.
Three decades of a lesson learned from Thailand: compulsory service for dentist workforce distribution
Authors: Arunratanothai Tanit , Booncharoen Ravisorn , Suwankomolkul Sirapop , Limpuangthip Nareudee
Published: January 2022

Background

Thailand has encountered an imbalanced dentist distribution and an internal brain drain of dentists from public to private health care facilities. To tackle these challenges, the compulsory service (CS) program, which has been initially implemented for physicians, was extended for dentists.

Method

This policy and workforce document review describes the background, development, and policy implementation of the CS program in Thailand during the past three decades. Outcomes after policy implementation and future directions are also discussed. The information was gathered from the relevant policy and workforce documents available from 1961 to 2021.

Results

In Thailand, junior dentists, specifically newly graduates, have to enroll in the CS program by working as oral health practitioners in public hospitals for at least 3 years. Dentists must pay a maximum fine of 400 000 baht (~ 12 571 USD) if they wish to skip the program. This fine is lowered according to the number of attending years in the program. CS program conditions are related to each university’s admission track. The CS enrolled dentists receive several financial and non-financial benefits, including educational, employment-related, and living provisions. Altogether, successive Thai governments have launched directive policies to increase dentist distribution in rural areas and their retention in public hospitals. These policies have been implemented in 3 stages: (1) increase production of new dentists, (2) allocation of newly dental graduates to public hospitals, and (3) provide benefits for working in public hospitals.

Conclusion

During the past three decades, several public policies have been implemented to improve dentist retention and distribution to public hospitals across Thailand, particularly in rural areas. The present CS program may not completely resolve the oral health inequalities because the dentist retention rate in public hospitals depends on multi-dimensional considerations. Further modifications on the CS program and future well-planned policies are needed.
Longitudinal study of the impact of three major regulations on the Korean pharmaceutical industry in the last 30 years
Authors: Um Seung In , Sohn Uy Dong , Jung Sun-Young , You Seung-Hun , Kim Changone , Lee Sora , Lee Heesang
Published: January 2022

Background

The pharmaceutical industry is heavily regulated. Partly for this reason, new drugs generally take over 10 years from the product development stage to market entry. Although regulations affect the pharmaceutical industry over a long period, previous studies investigating the impact of new regulatory policies have usually focused on the short period before and after implementing that policy. Therefore, the purpose of this study is to examine whether and how significantly regulatory policies affect long-term innovation in the pharmaceutical industry in Korea.

Methods

This study focused on three significant regulatory policies: the introduction of the product patent system, changes in the Good Manufacturing Practice (GMP) system, and the Drug Expenditure Rationalization Plan (DERP). The study used interrupted time series (ITS) analysis to investigate the long-term impacts of the policies before and after implementation.

Results

Our results show that introducing the product patent system in 1987 significantly increased the number of Korean patent applications. The effect of the revised GMP policies was also statistically significant, both before and after implementation and between pre-emptive companies and non-pre-emptive ones. However, due to the companies' negotiations with the regulatory authorities or the regulatory system that links drug approval and price evaluation, the DERP did not significantly delay new drug registration in Korea.

Conclusion

This study showed that the policies of the product patent system, GMP policies, and DERP regulations have significantly encouraged pharmaceutical companies to strive to meet regulatory requirements and promote innovation in Korea. The study suggests that it is necessary for companies to pre-emptively respond to systemic changes in development and production strategies to deal with regulatory changes and achieve sustainable growth. Also, our study results indicate that since government policies motivate the innovative system of the pharmaceutical industry, governmental authorities, when formulating pharmaceutical policies, need to consider the impact on the long-term innovation of the industry.
Assessing the impact of the Good Samaritan Law in the state of Connecticut: a system dynamics approach
Authors: Sabounchi Nasim S. , Heckmann Rebekah , D’Onofrio Gail , Walker Jennifer , Heimer Robert
Published: January 2022

Background

Although Good Samaritan laws (GSLs) have been widely adopted throughout the United States, their efficacy in individual states is often unknown. This paper offers an approach for assessing the impact of GSLs and insight for policy-makers and public health officials who wish to know whether they should expect to see outcomes from similar policy interventions.

Methods

Utilizing a system dynamics (SD) modeling approach, the research team conducted a policy evaluation to determine the impact of GSLs on opioid use disorder (OUD) in Connecticut and evaluated the GSL based upon the following health outcomes: (1) emergency department (ED) visits for overdose, (2) behavioral changes of bystanders, and (3) overdose deaths.

Results

The simulation model suggests that Connecticut’s GSL has not yet affected overdose deaths but has resulted in bystander behavioral changes, such as increased 911 calls for overdose. ED visits have increased as the number of opioid users has increased.

Conclusions

The simulation results indicate that the number of opioid-related deaths will continue to increase and that the GSL alone cannot effectively control the crisis. However, the SD approach that was used will allow policymakers to evaluate the effectiveness of the GSL over time using a simulation framework. This SD model demonstrates great potential by producing simulations that allow policymakers to assess multiple strategies for combating the opioid crisis and select optimal public health interventions.
Clinical and patient-centered implementation outcomes of mHealth interventions for type 2 diabetes in low-and-middle income countries: a systematic review
Authors: Mokaya Moses , Kyallo Florence , Vangoitsenhoven Roman , Matthys Christophe
Published: January 2022

Background

The prevalence of Type 2 Diabetes is rising in Low- and Middle-Income Countries (LMICs), affecting all age categories and resulting in huge socioeconomic implications. Mobile health (mHealth) is a potential high-impact approach to improve clinical and patient-centered outcomes despite the barriers of cost, language, literacy, and internet connectivity. Therefore, it is valuable to examine the clinical and implementation outcomes of mHealth interventions for Type 2 Diabetes in LMICs.

Methods

The Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) guidelines were applied in framing and reporting the review criteria. A systematic search of Cochrane Library, Web of Science, PubMed, Scopus, and Ovid databases was performed through a combination of search terms. Randomized Controlled Trials (RCTs) and cohort studies published in English between January 2010 and August 2021 were included. Risk of bias for missing results in the included studies was assessed using the Cochrane risk-of-bias tool for randomized trials (RoB 2). Quantitative and qualitative methods were used to synthesize the results.

Results

The search identified a total of 1161 articles. Thirty studies from 14 LMICs met the eligibility criteria. On clinical outcomes, 12 and 9 studies reported on glycated hemoglobin (HbA1c )and fasting blood glucose (FBG) respectively. Text messages was the most commonly applied mHealth approach, used in 19 out of the 30 studies. Ten out of the 12 studies (83.3%) that reported on HbA1c had a percentage difference of <0.3% between the mHealth intervention and the comparison group. Additionally, studies with longer intervention periods had higher effect size and percentage difference on HbA1c (1.52 to 2.92%). Patient-centred implementation outcomes were reported variedly, where feasibility was reported in all studies. Acceptability was reported in nine studies, appropriateness in six studies and cost in four studies. mHealth evidence reporting and assessment (mERA) guidelines were not applied in all the studies in this review.  

Conclusion

mHealth interventions in LMICs are associated with clinically significant effectiveness on HbA1 but have low effectiveness on FBG. The application of mERA guidelines may standardize reporting of patient-centered implementation outcomes in LMICs.

Trial registration

PROSPERO: Registration ID 154209.
Importance of characterising sleep breaks within the 24-h movement behaviour framework
Authors: Sabia Séverine , Yerramalla Manasa Shanta , Liu-Ambrose Teresa
Published: January 2022

Accelerometers measure the acceleration of the body part they are attached and allow to estimate time spent in activity levels (sedentary behaviour, light, and moderate-to-vigorous physical activity) and sleep over a 24-h period for several consecutive days. These advantages come with the challenges to analyse the large amount of data while integrating dimensions of both physical activity/sedentary behaviour and sleep domains. This commentary raises the questions of 1) how to classify sleep breaks (i.e. wake after sleep onset) during the night within the 24-h movement behaviour framework and 2) how to assess their impact on health while also accounting for night time sleep duration and time in sedentary behaviour and physical activity during the day. The authors advocate for future collaborations between researchers from the physical activity/sedentary behaviour and sleep research fields to ensure appropriate analysis and interpretation of the tremendous amount of data recorded by the newer generation accelerometers. This is the only way forward to provide meaningfully accurate evidence to inform future 24-h movement behaviour guidelines.
Bacterial infections exacerbate myeloma bone disease
Authors: Liu Rui , Zhong Yuping , Chen Rui , Chen Shiyi , Huang Yazhu , Liu Huan
Published: January 2022

Multiple myeloma is characterized by osteolytic lesions caused by reduced bone formation and activated bone resorption. An important feature of myeloma is a failure of bone healing after successful treatment. In this work, clinical studies indicated a highly positive correlation between bone marrow bacteria abundance and bone lesion numbers of myeloma patients in complete remission. Coculture experiments demonstrated that marrow Escherichia coli (E. coli) promotes osteoclast differentiation and inhibits osteoblast differentiation. Mechanism studies showed that E. coli lipopolysaccharides (LPS) activated NF-κB p65 signaling and reduced phosphorylated smad1/5/9 binding ability with RUNX2 promoter, leading to decreased RUNX2 expression in osteoblast progenitors. Additionally, LPS enhanced phosphorylated NF-κB p65 binding ability with NFATc1 promoter, leading to increased NFATc1 expression in osteoclast progenitors. In vivo studies revealed E. coli contributes to osteolytic bone lesion, and elimination of E. coli infection assists healing of bone lesion in mouse model of myeloma in complete remission. These findings establish a heretofore unrecognized effect for E. coli in the genesis of myeloma bone disease and suggest a new treatment strategy.