bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study protocol for an efficacy trial of the “PrEP for Health” intervention to increase HIV PrEP use among people who inject drugs
Authors: Bazzi Angela R. , Bordeu Michelle , Baumgartner Katrina , Sproesser Darien M. , Bositis Christopher M. , Krakower Douglas S. , Mimiaga Matthew J. , Biello Katie B. 
Published: March 2023

Abstract
Background
HIV incidence has recently increased among people who inject drugs (PWID) across the United States, with outbreaks occurring in states with long-standing syringe service programs (SSPs) including Massachusetts (MA). Antiretroviral pre-exposure prophylaxis (PrEP) is an evidence-based HIV prevention strategy recommended for PWID, but uptake in this marginalized population is extraordinarily low.

Methods
We describe the design and procedures for a National Institute on Drug Abuse (NIDA)-funded (R01) randomized controlled trial (RCT) testing the efficacy of “PrEP for Health,” a multicomponent behavioral intervention to increase PrEP uptake, adherence, and persistence among HIV-negative PWID attending SSPs in two areas of the U.S. Northeast that are heavily affected by injection-related HIV transmission. Participants are equally randomized to receive the “PrEP for Health” intervention (involving individually tailored HIV and PrEP education, motivational interviewing, problem-solving skills and planning, and ongoing navigation support) or an enhanced standard of care (eSOC) control condition involving a brief educational video on the utility of PrEP for HIV prevention. Co-primary outcomes are PrEP uptake (using medical/pharmacy records) and adherence (using tenofovir quantification in hair samples); a secondary outcome is PrEP persistence (using medical/pharmacy records) over 12 months. Major assessments occur at baseline, 1-, 3-, 6-, and 12-month follow-up visits. Planned analyses will examine intervention efficacy, specific hypothesized conceptual mediators of the intervention effect (e.g., self-perceived HIV risk; PrEP knowledge, interest in use, motivation, and behavioral skills) and epidemiologically linked moderators (e.g., age; gender; condomless vaginal or anal sex).

Discussion
Findings from our extensive preliminary research with the study population revealed that a multicomponent, theory-based intervention targeting PrEP knowledge, motivation, self-efficacy, behavioral skills, and structural barriers to PrEP access is urgently needed for PWID who are at risk of HIV acquisition. We also learned that SSPs represent a highly acceptable service setting for delivering such interventions. In this study, we are evaluating the efficacy of the “PrEP for Health” intervention. If efficacious, findings from our implementation evaluation could help guide its dissemination to diverse SSPs and possibly other community-based settings accessed by this population.

Trial registration
ClinicalTrials.gov number NCT04430257, registered June 12, 2020.
Race/ethnicity-specific associations between breastfeeding information source and breastfeeding rates among U.S. women
Authors: Quintero Stephanie M. , Strassle Paula D. , Londoño Tobón Amalia , Ponce Stephanie , Alhomsi Alia , Maldonado Ana I. , Ko Jamie S. , Wilkerson Miciah J. , Nápoles Anna María 
Published: March 2023

Abstract
Background
Despite evidence of the impact of breastfeeding information on breastfeeding rates, it is unknown if information sources and impact vary by race/ethnicity, thus this study assessed race/ethnicity-specific associations between breastfeeding information sources and breastfeeding.

Methods
We used data from the 2016–2019 Pregnancy Risk Assessment Monitoring System. Race/ethnicity-stratified multinomial logistic regression was used to estimate associations between information source (e.g., family/friends) and breastfeeding rates (0 weeks/none, < 10 weeks, or ≥ 10 weeks; < 10 weeks and ≥ 10 weeks = any breastfeeding). All analyses were weighted to be nationally representative.

Results
Among 5,945,018 women (weighted), 88% reported initiating breastfeeding (≥ 10 weeks = 70%). Information from family/friends (< 10 weeks: aORs = 1.58–2.14; ≥ 10 weeks: aORs = 1.63–2.64) and breastfeeding support groups (< 10 weeks: aORs = 1.31–1.76; ≥ 10 weeks: aORs = 1.42–2.77) were consistently associated with breastfeeding and duration across most racial/ethnic groups; effects were consistently smaller among Alaska Native, Black, and Hispanic women (vs White women). Over half of American Indian and one-quarter of Black women reported not breastfeeding/stopping breastfeeding due to return to school/work concerns.

Conclusions
Associations between breastfeeding information source and breastfeeding rates vary across race/ethnicity. Culturally tailored breastfeeding information and support from family/friends and support groups could help reduce breastfeeding disparities. Additional measures are needed to address disparities related to concerns about return to work/school.
Induced leg length inequality affects pelvis orientation during upright standing immediately following a sit-to-stand transfer: a pre-post measurement study
Authors: Vella Simon P. , Swain Michael , Downie Aron , Howarth Samuel J. , Funabashi Martha , Engel Roger M. 
Published: March 2023

Abstract
Background
Leg length inequality (LLI) greater than 20 mm has been associated with low back pain (LBP) and its correction is clinically recommended. Much less is known about the biomechanical effects that LLI below 15 mm has on pelvis orientation.

Methods
Twenty-two adult participants (8 female) aged between 18 and 30 years without LBP were enrolled in the study and completed a series of sit-to-stand trials with no heel-lift (0 mm baseline) and heel-lifts of varying heights (5, 9 and 12 mm) placed in their right shoe. Three-dimensional kinematic data were obtained from the lower extremities, pelvis and thorax. Additional kinematic data were obtained from the left and right sides of the pelvis. The global orientation of the whole pelvis and relative orientation between the left and right sides of the pelvis were obtained in upright standing immediately upon completion of the sit-to-stand movement. Repeated measures ANOVAs were used to detect differences in sample means across the different levels of heel-lift (0, 5, 9, and 12 mm). The tests for within-subject effects determined overall significant differences between the means at the different levels of heel-lift induced LLI. Partial Eta-Squared was used to express the size for the main effect of heel-lift height. For each level of heel-lift, the estimated marginal mean and 95% confidence interval (95%CI) values of pelvis angles were illustrated graphically.

Results
Left frontal plane rotation of the pelvis increased (p = 0.001), that is, the left side of the pelvis was lower than the right side of the pelvis, and anterior tilt of the pelvis decreased (p = 0.020) with a heel-lift height (applied on the right) as low as 5 mm. A significant main effect of heel-lift was only observed for the norm of rotations about all three axes for relative-pelvis orientation (p = 0.034). Post-hoc analyses did not reveal any statistically significant differences between the heel-lifts and the 0 mm baseline (p≥0.072).

Conclusion
These findings suggest that correcting leg length inequality below the recommended threshold of 20 mm may influence pelvic orientation. Future work can investigate the effects of the altered orientations on spine loading and the clinical effects of corrections to minor leg length inequality.
Cost-effectiveness and budget impact of heat-stable carbetocin compared to oxytocin and misoprostol for the prevention of postpartum hemorrhage (PPH) in women giving birth in India
Authors: Cook John R. , Saxena Kunal , Taylor Catharine , Jacobs Jeffrey L. 
Published: March 2023

Abstract
Introduction
Low- and middle-income countries (LMICs) are committed to achieving the Sustainable Development Goal 3.1 to reduce maternal mortality. The Ministry of Health and Family Welfare of India recommends prophylactic uterotonic administration to every woman following delivery to reduce the risk of postpartum hemorrhage (PPH), as PPH is the leading cause of maternal mortality in LMICs, including India. In 2018, the World Health Organization first recognized heat-stable carbetocin for PPH prevention. Governments are now considering its introduction into their public health systems.

Methods
A decision-tree model was developed from the public healthcare system perspective to compare the value of heat-stable carbetocin versus oxytocin and misoprostol among women giving birth in public sector healthcare facilities in India. The model accounted for differences in PPH risk and costs based on mode of delivery and healthcare setting, as well as provider behavior to mitigate quality concerns of oxytocin. Model outcomes for each prophylactic uterotonic included the number of PPH events, DALYs due to PPH, deaths due to PPH, and direct medical care costs. The budget impact was estimated based on projected uterotonic uptake between 2022–2026.

Results
Compared to oxytocin, heat-stable carbetocin avoided 5,468 additional PPH events, 5 deaths, and 244 DALYs per 100,000 births. Projected direct medical costs to the public healthcare system were lowered by US $171,700 (₹12.8 million; exchange rate of ₹74.65 = US$1 from 2 Feb 2022) per 100,000 births. Benefits were even greater when compared to misoprostol (7,032 fewer PPH events, 10 fewer deaths, 470 fewer DALYs, and $230,248 saved per 100,000 births). In the budget impact analysis, India’s public health system is projected to save US$11.4 million (₹849 million) over the next five years if the market share for heat-stable carbetocin grows to 19% of prophylactic uterotonics administered.

Conclusions
Heat-stable carbetocin is expected to reduce the number of PPH events and deaths, avoid more DALYs, and reduce costs to the public healthcare system of India. Greater adoption of heat-stable carbetocin for the prevention of PPH could advance India’s efforts to achieve its maternal health goals and increase efficiency of its public health spending.
Health economic evaluation of preventive digital public health interventions using decision-analytic modelling: a systematized review
Authors: Lange Oliver 
Published: March 2023

AbstractBackgroundDigital public health (DiPH) provides novel approaches for prevention, potentially leading to long-term health benefits in resource-limited health systems. However, cost-effectiveness of DiPH interventions is unclear. This systematized review investigates the use of decision-analytic modelling in health economic evaluations of DiPH primary prevention and health promotion interventions, focusing on intervention’s design, methods used, results, and reporting quality.MethodsPubMed, CINAHL, and Web of Science were searched for studies of decision-analytic economic evaluations of digital interventions in primary prevention or health promotion, published up to June 2022. Intervention characteristics and selected items were extracted based on the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Incremental cost-effectiveness ratios (ICERs) were then extracted and price-adjusted to compare the economic evaluation results. Finally, the included studies’ reporting quality was assessed by building a score using CHEERS.ResultsThe database search (including search update) produced 2,273 hits. After removing duplicates, 1,434 titles and abstracts were screened. Of the 89 studies meeting the full-text search criteria, 14 were ultimately reviewed. The most common targets were physical activity (five studies) and weight loss (four). Digital applications include text messages, web-based inventions, app-based interventions, e-learning devices, and the promotion of smartphone apps. The mean ICER of the 12 studies using quality-adjusted life years (QALYs) is €20,955 per QALY (min. − €3,949; max. €114,211). The mean of reported CHEERS items per study is 81% (min. 59%; max. 91%).ConclusionsThis review only includes primary prevention and health promotion, and thus excludes other DiPH fields (e.g. secondary prevention). It also focuses on decision-analytic models, excluding study-based economic evaluations. Standard methods of economic evaluation could be adapted more to the specifics of DiPH by measuring the effectiveness of more current technologies through alternative methods, incorporating a societal perspective, and more clearly defining comparators. Nevertheless, the review demonstrates using common thresholds that the new field of DiPH shows potential for cost-effective preventive interventions.
Systematic evaluation of membrane-camouflaged nanoparticles in neutralizing Clostridium perfringens ε-toxin
Authors: Xu Jinglin , Li Dongxue , Kang Lin , Liu Tingting , Huang Jing , Li Jiaxin , Lv Jing , Wang Jing , Gao Shan , Li Yanwei , Yuan Bing , Zhao Baohua , Wang Jinglin , Xin Wenwen 
Published: March 2023

AbstractClostridium perfringens ε-toxin (ETX) is the main toxin leading to enterotoxemia of sheep and goats and is classified as a potential biological weapon. In addition, no effective treatment drug is currently available in clinical practice for this toxin. We developed membrane-camouflaged nanoparticles (MNPs) with different membrane origins to neutralize ETX and protect the host from fatal ETX intoxication. We evaluated the safety and therapeutic efficacy of these MNPs in vitro and in vivo. Compared with membranes from karyocytes, such as Madin-Darby canine kidney (MDCK) cells and mouse neuroblastoma N2a cells (N2a cells), membrane from erythrocytes, which do not induce any immune response, are superior in safety. The protective ability of MNPs was evaluated by intravenous injection and lung delivery. We demonstrate that nebulized inhalation is as safe as intravenous injection and that both modalities can effectively protect mice against ETX. In particular, pulmonary delivery of nanoparticles more effectively treated the challenge of inhaled toxins than intravenously injected nanoparticles. Moreover, MNPs can alter the biological distribution of ETX among different organs in the body, and ETX was captured, neutralized and slowly delivered to the liver and spleen, where nanoparticles with ETX could be phagocytized and metabolized. This demonstrates how MNPs treat toxin infections in vivo. Finally, we injected the MNPs into mice in advance to find out whether MNPs can provide preventive protection, and the results showed that the long-cycle MNPs could provide at least a 3-day protection in mice. These findings demonstrate that MNPs provide safe and effective protection against ETX intoxication, provide new insights into membrane choices and delivery routes of nanoparticles, and new evidence of the ability of nanoparticles to provide preventive protection against infections.
Graphical Abstract
An integrated approach of network pharmacology, molecular docking, and experimental verification uncovers kaempferol as the effective modulator of HSD17B1 for treatment of endometrial cancer
Authors: Ruan Guan-Yu , Ye Li-Xiang , Lin Jian-Song , Lin Hong-Yu , Yu Li-Rui , Wang Cheng-Yan , Mao Xiao-Dan , Zhang Shui-Hua , Sun Peng-Ming 
Published: March 2023

AbstractBackgroundEndometrial cancer (EC) is one of the most common gynecological malignancies globally, and the development of innovative, effective drugs against EC remains a key issue. Phytoestrogen kaempferol exhibits anti-cancer effects, but the action mechanisms are still unclear.MethodMTT assays, colony-forming assays, flow cytometry, scratch healing, and transwell assays were used to evaluate the proliferation, apoptosis, cell cycle, migration, and invasion of both ER-subtype EC cells. Xenograft experiments were used to assess the effects of kaempferol inhibition on tumor growth. Next-generation RNA sequencing was used to compare the gene expression levels in vehicle-treated versus kaempferol-treated Ishikawa and HEC-1-A cells. A network pharmacology and molecular docking technique were applied to identify the anti-cancer mechanism of kaempferol, including the building of target-pathway network. GO analysis and KEGG pathway enrichment analysis were used to identify cancer-related targets. Finally, the study validated the mRNA and protein expression using real-time quantitative PCR, western blotting, and immunohistochemical analysis.ResultsKaempferol was found to suppress the proliferation, promote apoptosis, and limit the tumor-forming, scratch healing, invasion, and migration capacities of EC cells. Kaempferol inhibited tumor growth and promotes apoptosis in a human endometrial cancer xenograft mouse model. No significant toxicity of kaempferol was found in human monocytes and normal cell lines at non-cytotoxic concentrations. No adverse effects or significant changes in body weight or organ coefficients were observed in 3–7 weeks’ kaempferol-treated animals. The RNA sequencing, network pharmacology, and molecular docking approaches identified the overall survival-related differentially expressed gene HSD17B1. Interestingly, kaempferol upregulated HSD17B1 expression and sensitivity in ER-negative EC cells. Kaempferol differentially regulated PPARG expression in EC cells of different ER subtypes, independent of its effect on ESR1. HSD17B1 and HSD17B1-associated genes, such as ESR1, ESRRA, PPARG, AKT1, and AKR1C1\2\3, were involved in several estrogen metabolism pathways, such as steroid binding, 17-beta-hydroxysteroid dehydrogenase (NADP+) activity, steroid hormone biosynthesis, and regulation of hormone levels. The molecular basis of the effects of kaempferol treatment was evaluated.ConclusionsKaempferol is a novel therapeutic candidate for EC via HSD17B1-related estrogen metabolism pathways. These results provide new insights into the efficiency of the medical translation of phytoestrogens.
Endocannabinergic modulation of central serotonergic activity in healthy human volunteers
Authors: Emons Barbara , Arning Larissa , Makulla Vera-Estelle , Suchy Maria-Theresia , Tsikas Dimitrios , Lücke Thomas , Epplen Jörg T. , Juckel Georg , Roser Patrik 
Published: March 2023

Abstract
Background
The serotonergic and the endocannabinoid system are involved in the etiology of depression. Depressive patients exhibit low serotonergic activity and decreased level of the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2AG). Since the cannabinoid (CB) 1 receptor is activated by endogenous ligands such as AEA and 2AG, whose concentration are controlled by the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase, respectively, we investigated the effects on serotonergic utilization. In this study, we investigated the impact of the rs1049353 single-nucleotide polymorphism (SNP) of the cannabinoid receptor 1 (CNR1) gene, which codes the endocannabinoid CB1 receptor, and the rs324420 SNP of the FAAH gene on the serotonergic and endocannabinoid system in 59 healthy volunteers.

Methods
Serotonergic activity was measured by loudness dependence of auditory-evoked potentials (LDAEP). Plasma concentrations of AEA, 2AG and its inactive isomer 1AG were determined by mass spectrometry. Genotyping of two SNPs (rs1049353, rs344420) was conducted by polymerase chain reaction (PCR) and differential enzymatic analysis with the PCR restriction fragment length polymorphism method.

Results
Genotype distributions by serotonergic activity or endocannabinoid concentration showed no differences. However, after detailed consideration of the CNR1-A-allele-carriers, a reduced AEA (A-allele-carrier M = 0.66, SD = 0.24; GG genotype M = 0.72, SD = 0.24) and 2AG (A-allele-carriers M = 0.70, SD = 0.33; GG genotype M = 1.03, SD = 0.83) plasma concentration and an association between the serotonergic activity and the concentrations of AEA and 2AG has been observed.

Conclusions
Our results suggest that carriers of the CNR1-A allele may be more susceptible to developing depression.
Effects of repetitive functional magnetic stimulation in the sacral nerve in patients with neurogenic detrusor overactivity after suprasacral spinal cord injury: a study protocol for a randomized controlled trial
Authors: Li Jiyang , Wang Jianxiong , Hu Yue , Jian Rui , Zhao Yulu , Li Dan , Wan Tenggang , Jike Wuga , Xu Fangyuan , Huang Maomao 
Published: March 2023

Abstract

Background
Neurogenic detrusor overactivity (NDO) is a serious and common complication after spinal cord injury, affecting patients’ quality of life seriously. Therefore, we developed this research protocol to evaluate the efficacy of repetitive functional magnetic stimulation (rFMS) in the sacral nerve in patients with neurogenic detrusor overactivity (NDO) after suprasacral spinal cord injury (SCI) and provide more options for rFMS in treating NDO after suprasacral SCI.

Methods
This study is a single-center, randomized, parallel-group clinical trial. We will recruit the patients with NDO after suprasacral SCI in the Rehabilitation Department of the Affiliated Hospital of Southwest Medical University from September 2022 to August 2023. They will be assigned to the rFMS group and the sham stimulation group randomly. The sample size is 66, with 33 patients in each group. The rFMS group will receive real rFMS treatment of the sacral nerve (100% stimulation intensity, 5 Hz, 20 min each time, five times a week), and the sham group will receive sham stimulation. Both groups will receive similar treatment strategies, including medication, standard urine management, acupuncture treatment, and health education. The bladder compliance (bladder capacity/detrusor pressure) and pudendal nerve electromyography will be evaluated at baseline, 8th week of treatment. The residual volume of the bladder and bladder diary will be recorded once a week during 8 weeks of treatments. SCI-QOL and NBSS will be evaluated at baseline, the 4th and 8th week of treatment. In addition, the above assessments will be followed up at 8 weeks after the end of treatment.

Discussion
It is expected that the bladder function, symptoms, and quality of life might be significantly improved after rFMS of the sacral nerve.

Trial registration
The China Clinical Trials Registry has approved this study, registration number: ChiCTR2100045148. Registered on April 7, 2021.