bluuebunny/crossref_metadata_2025_split huggingface dataset:
L-arginine and aged garlic extract for the prevention of migraine: a study protocol for a randomised, double-blind, placebo-controlled, phase-II trial (LARGE trial)
Authors: Chaliha Devahuti R. , Vaccarezza Mauro , Corti Emily , Takechi Ryusuke , Dhaliwal Satvinder S. , Drummond Peter , Visser Eric , Chen Fred K. , Charng Jason , Lam Virginie , Mamo John C.L. 
Published: March 2023

Abstract
Background
Migraine is a common and distressing neurological condition characterised by recurrent throbbing headaches, nausea and heightened sensitivity to light and sound. Accumulating evidence suggests that cerebral arteries dilate during migraine, causing distal microvessels to constrict, which could activate nociceptors and cause onset of headache pain. If so, preventing or attenuating chronic microvascular constriction, and promoting a dilatory phenotype, may reduce frequency and/or severity of migraines. The primary aim of the L-Arginine and Aged Garlic Extract (LARGE) trial is to investigate whether oral treatment with dietary nutraceuticals, L-arginine and aged garlic extract (AGE), both systemic vasodilatory agents, will alleviate migraine frequency, duration and severity in adults with chronic frequent episodic migraines.

Methods
The study is a randomised double-blind placebo-controlled phase-II single-site clinical trial conducted in Perth, Australia. The target sample is to recruit 240 participants diagnosed with chronic frequent episodic migraines between 18 and 80 years of age. Participants will be randomised to one of four treatment groups for 14 weeks (placebo induction for 2 weeks, followed by 12 weeks on one of the respective treatment arms): placebo, L-arginine, AGE, or a combination of L-arginine and AGE. The doses of L-arginine and AGE are 1.5 g and 1 g daily, respectively. The primary outcome is to assess migraine response using change in migraine frequency and intensity between baseline and 12 weeks. Secondary outcomes include the impact of L-arginine and/or AGE on photosensitivity, retinal vessel changes, and blood biomarker concentrations of vascular tone, following a 12-week intervention.

Discussion
The protocol describes the oral administration of 2 nutraceutical-based interventions as possible prophylactic treatments for chronic frequent episodic migraines, with potential for direct clinical translation of outcomes. Potential limitations of the study include the fixed-dose design of each treatment arm and that in vivo neuroimaging methods, such as magnetic resonance imaging (MRI), will not be conducted to determine putative cerebro-vasodilatory changes to coincide with the outcome measures. Dose-response studies may be indicated.

Trial registration
The trial was retrospectively registered with the Australian New Zealand Clinical Trials Registry ACTRN12621001476820 (Universal Trial Number: U1111-1268-1117) on 04/08/2021. This is protocol version 1, submitted on 25/11/2022.
Impact of BMI and smoking in adolescence and at the start of pregnancy on birth weight
Authors: Bramsved Rebecka , Mårild Staffan , Bygdell Maria , Kindblom Jenny M. , Lindh Ingela 
Published: March 2023

Abstract
Background
Birth weight is an indicator of intra-uterine conditions but also a determinant for future health. The importance of preconception health for a healthy birth weight has been emphasized, but evidence is lacking on how modifiable factors in adolescence, such as body mass index (BMI) and smoking, affect future pregnancy outcome. We evaluated associations between BMI and smoking in adolescence and at the start of pregnancy and birth weight of the first-born child.

Methods
This longitudinal study included 1256 mothers, born 1962–1992, and their first-born children, born between 1982–2016. Self-reported questionnaire information on weight, height and smoking at age 19 was cross-linked with national register data obtained at the start of pregnancy and with the birth weights of the children. Univariable and multivariable linear regressions were performed to determine the impact of maternal factors at 19 years of age and at the start of the pregnancy respectively, and the importance of BMI status at these points of time for the birth weight of the first child.

Results
BMI and smoking at the start of the pregnancy displayed strong associations with birth weight in a multivariable analysis, BMI with a positive association of 14.9 g per BMI unit (95% CI 6.0; 23.8 p = 0.001) and smoking with a negative association of 180.5 g (95% CI -275.7; -85.4) p = 0.0002). Smoking and BMI at 19 years of age did not show this association. Maternal birth weight showed significant associations in models at both time-points. Becoming overweight between age 19 and the start of the pregnancy was associated with a significantly higher birth weight (144.6 (95% CI 70.7;218.5) p = 0.0002) compared to mothers with normal weight at both time points.

Conclusions
Our findings indicate that the time period between adolescence and first pregnancy could be a window of opportunity for targeted health promotion to prevent intergenerational transmission of obesity.
Scoping review of sexual and reproductive healthcare for men in the MENA (Middle East and North Africa) region: a handful of paradoxes?
Authors: El Ansari Walid , Arafa Mohamed , Elbardisi Haitham , Majzoub Ahmad , Mahdi Mohammed , Albakr Ahmed , AlRumaihi Khalid , Al Ansari Abdulla 
Published: March 2023

AbstractBackgroundNo study appraised the knowledge gaps and factors impacting men’s sexual and reproductive health (SRH) in MENA (Middle East and North Africa). The current scoping review undertook this task.MethodsWe searched PubMed and Web of Science (WoS) electronic databases for original articles on men’s SRH published from MENA. Data was extracted from the selected articles and mapped out employing the WHO framework for operationalising SRH. Analyses and data synthesis identified the factors impacting on men’s experiences of and access to SRH.ResultsA total of 98 articles met the inclusion criteria and were included in the analysis. The majority of studies focused on HIV and other sexually transmissible infections (67%); followed by comprehensive education and information (10%); contraception counselling/provision (9%); sexual function and psychosexual counselling (5%); fertility care (8%); and gender-based violence prevention, support/care (1%). There were no studies on antenatal/intrapartum/postnatal care and on safe abortion care (0% for both). Conceptually, there was lack of knowledge of the different domains of men’s SRH, with negative attitudes, and many misconceptions; as well as a deficiency of health system policies, strategies and interventions for SRH.ConclusionMen’s SRH is not sufficiently prioritized. We observed five ‘paradoxes’: strong focus on HIV/AIDS, when MENA has low prevalence of HIV; weak focus on both fertility and sexual dysfunctions, despite their high prevalence in MENA; no publications on men’s involvement in sexual gender-based violence, despite its frequency across MENA; no studies of men’s involvement in antenatal/intrapartum/postnatal care, despite the international literature valuing such involvement; and, many studies identifying lack of SRH knowledge, but no publications on policies and strategies addressing such shortcoming. These ‘mismatches’ suggest the necessity for efforts to enhance the education of the general population and healthcare workers, as well as improvements across MENA health systems, with future research examining their effects on men’s SRH.
A needs assessment for self-management services for adults awaiting community-based mental health services
Authors: Jennings Cally , Singh Ben , Oni Helen , Mazzacano Anna , Maher Carol 
Published: March 2023

Abstract
Background
High demand for services has resulted in lengthy waiting times being experienced across mental health services, both across Australia and internationally. Timely access to services is necessary to optimise the effectiveness of treatment, and prevent further mental health decline, risk of suicidality and hospitalisation for clients waiting for services to commence. The present study aims to better understand the experiences of individuals who are waiting for ongoing mental health services to commence and their preferences for additional support whilst on the waitlist, as a means to recommend alternative supports.

Methods
A link to the cross-sectional, anonymous survey was sent via text message to 2,147 clients of a mental health service, with a reminder text message sent approximately one week subsequent to those who did not opt out of the communication. Eligibility criteria included having been a client of the service in the previous 12 months, having spent time on the waiting list, being aged 16 or over and having sufficient English proficiency.

Results
A total of 334 participants responded to the needs assessment survey, 277 (82.9%) of which resided in the metropolitan region and 57 (17.1%) residing in the country region. Of the respondents, the majority presented with generalised anxiety/panic attacks (n = 205, 61.4%), followed by life stressors (e.g., financial concerns, relationships, n = 196, 58.7%) and lack of motivation/loss of interest (n = 196, 58.7%). Most respondents (52.7%) waited 4–12 months for ongoing services to commence and almost half (47%) reported that their mental health deteriorated during this time. Of the additional support options, most participants expressed interest in additional mental health supports (78.4%, n = 262), such as telephone support and access to online materials. There was significant interest in other supports such as exercise support (57.4%, n = 192), sleep education (56.6%, n = 190) and healthy eating support (41%, n = 137).

Conclusion
Mental health services are experiencing significant waiting times, increasing the risk of mental health deterioration for persons waiting for services to commence. However, the findings demonstrate that there is interest for alternative support options, such as lifestyle interventions, in the interim. Desire for lifestyle support services, particularly in-person exercise programs and self-directed sleep, was especially high amongst the population of respondents within this study. Future work to rigorously develop and evaluate such lifestyle support services for mental health clients is warranted.
Evaluation of the predictive value of the body-mass-index choosing perforator flaps from different donor sites
Authors: Mett Tobias R. , Boetger-Bolten Stephanie , Bucher Florian , Vogt Peter M. 
Published: March 2023

Abstract
Background
Free flap design must fulfill different criteria to ensure functional and aesthetic reconstruction of different types of defects in different body areas. A four-dimensional planning concept was used including flap length, width, thickness and tissue composition. This study evaluates if body-mass-index (BMI) has a predictive value for flap design.

Methods
A prospective study including hospitalized patients in the Department of Plastic, Aesthetic, Hand and Reconstructive Surgery was conducted. Not taking into account the reason for admission, the patients were examined based on age, weight, height, BMI and sex. The areas of a potential harvest of free fasciocutaneous and perforator flaps were measured using ultrasound examination to determine the thickness of the subcutaneous layers and prove blood perfusion.

Results
Over the period of four months, a total of 101 patients (36 females and 65 males) were included in this study and gave written consent. No statistical significance regarding the demographic data such as age, sex and BMI could be identified. An average to high correlation between free flap thickness and BMI was shown for the thoracodorsal artery perforator (TDAP), anterior lateral thigh (ALT) and deep inferior epigastric perforator (DIEP) flap in both, male and female patients.
Free flaps of distal body parts such as the interosseous posterior flap, showed a lower correlation. No correlation using the Pearson coefficient could be found for age and volume.

Conclusion
Our study demonstrated that the BMI is a predictive indicator that can be used in the preoperative planning of reconstructions using free flaps. Depending on the defect location, the BMI can be considered to predict the thickness of the free flap and may influence the surgeon’s choice.
On the other hand, a lower correlation between BMI and flap thickness encourages the use of standard flaps if more volume is desired, as the DIEP flap might be sufficient even in normal-weight women. Flaps of distal body parts, such as the forearm or lower leg, are not prone to such predictions and require other selection criteria.
Sexual behaviors, contraception use and barriers among adolescents and young adults in rural Haiti
Authors: Masonbrink Abbey R. , Hurley Emily A. , Schuetz Nikolaus , Rodean Jonathan , Rupe Emily , Lewis Kemi , Boncoeur Marie Daphnée , Miller Melissa K. 
Published: March 2023

Abstract
Background
Adolescents and young adults (AYAs) in Haiti experience a high unintended pregnancy rate, in part due to unmet contraception needs. Little is known about AYA opinions of and experiences with contraception that may explain remaining gaps in coverage. We aimed to describe barriers and facilitators to contraception use among AYAs in Haiti.

Methods
We conducted a cross-sectional survey and semi-structured qualitative interviews with a convenience sample of AYA females aged 14–24 in two rural communities in Haiti. The survey and semi-structured interviews assessed demographics, sexual health and pregnancy prevention behaviors and explored contraception opinions and experiences according to Theory of Planned Behavior constructs: attitudes, subjective norms, and perceived behavioral control. We used descriptive statistics to report means and responses to Likert scale and multiple-choice questions. Guided by content analysis, we analyzed interview transcripts through inductive coding and team debriefing.

Results
Among 200 survey respondents, 94% reported any past vaginal sexual activity, and 43% reported ever being pregnant. A large majority were trying to avoid pregnancy (75%). At last sexual activity, 127 (64%) reported use of any contraceptive method; Among them, condoms were the most common method (80%). Among those with previous condom use, most reported use less than half the time (55%). AYAs were concerned about parental approval of birth control use (42%) and that their friends might think they are looking for sex (29%). About one-third felt uncomfortable going to a clinic to ask for birth control. In interviews, AYAs desired pregnancy prevention but frequently noted concerns about privacy and parental, community and healthcare provider judgement for seeking care for reproductive health needs. AYAs also noted a lack of contraception knowledge, evident by frequent misconceptions and associated fears.

Conclusion
Among AYAs in rural Haiti, a large majority were sexually active and desire pregnancy avoidance, but few were using effective contraception due to numerous concerns, including privacy and fear of judgement. Future efforts should address these identified concerns to prevent unintended pregnancy and improve maternal and reproductive health outcomes in this population.
Protocol and biomarker strategy for a multi-site randomized controlled trial examining biological mechanisms and dosing of active music engagement in children with acute lymphoblastic leukemia and lymphoma and parents
Authors: Robb Sheri L. , Russ Kristen A. , Holochwost Steven J. , Stegenga Kristin , Perkins Susan M. , Jacob Seethal A. , Henley Amanda K. , MacLean Jessica A. 
Published: March 2023

Abstract
Background
Music therapy is a standard palliative care service in many pediatric and adult hospitals; however, most research has focused on the use of music to improve psychosocial dimensions of health, without considering biological dimensions. This study builds on prior work examining psychosocial mechanisms of action underlying an Active Music Engagement (AME) intervention, designed to help manage emotional distress and improve positive health outcomes in young children with cancer and parents (caregivers), by examining its effects on biomarkers of stress and immune function.

Methods
This two-group randomized controlled trial (R01NR019190) is designed to examine biological mechanisms of effect and dose-response relationships of AME on child/parent stress during the consolidation phase of Acute B- or T-cell Lymphoblastic Leukemia (ALL) and T-cell Lymphoblastic Lymphoma (TLyLy) treatment. Child/parent dyads (n = 228) are stratified (by age, site, risk level) and randomized in blocks of four to the AME or attention control condition. Each group receives one session (30-minutes AME; 20-minutes control) during weekly clinic visits (4 weeks standard risk B-cell ALL; 8 weeks high risk B-cell ALL/T-cell ALL/TLyLy). Parents complete questionnaires at baseline and post-intervention. Child/parent salivary cortisol samples are taken pre- and post-session (sessions 1–4). Child blood samples are reserved from routine draws before sessions 1 and 4 (all participants) and session 8 (high risk participants). We will use linear mixed models to estimate AME’s effect on child/parent cortisol. Examining child/parent cortisol as mediators of AME effects on child and parent outcomes will be performed in an ANCOVA setting, fitting the appropriate mediation models using MPlus and then testing indirect effects using the percentile bootstrap approach. Graphical plots and non-linear repeated measures models will be used to examine dose-response relationship of AME on child/parent cortisol.

Discussion
During pediatric cancer treatment there are special challenges that must be considered when measuring cortisol and immune function. In this manuscript we discuss how we addressed three specific challenges through our trial design. Findings from this trial will increase mechanistic understanding of the effects of active music interventions on multiple biomarkers and understanding of dose-response effects, with direct implications for clinical practice.

Trial Registration
ClinicalTrials.gov: NCT04400071.
Association between exposure to multiple air pollutants, transportation noise and cause-specific mortality in adults in Switzerland
Authors: Vienneau Danielle , Stafoggia Massimo , Rodopoulou Sophia , Chen Jie , Atkinson Richard W. , Bauwelinck Mariska , Klompmaker Jochem O. , Oftedal Bente , Andersen Zorana J. , Janssen Nicole A. H. , So Rina , Lim Youn-Hee , Flückiger Benjamin , Ducret-Stich Regina , Röösli Martin , Probst-Hensch Nicole , Künzli Nino , Strak Maciek , Samoli Evangelia , de Hoogh Kees , Brunekreef Bert , Hoek Gerard 
Published: March 2023

Abstract
Background
Long-term exposure to air pollution and noise is detrimental to health; but studies that evaluated both remain limited. This study explores associations with natural and cause-specific mortality for a range of air pollutants and transportation noise.

Methods
Over 4 million adults in Switzerland were followed from 2000 to 2014. Exposure to PM2.5, PM2.5 components (Cu, Fe, S and Zn), NO2, black carbon (BC) and ozone (O3) from European models, and transportation noise from source-specific Swiss models, were assigned at baseline home addresses. Cox proportional hazards models, adjusted for individual and area-level covariates, were used to evaluate associations with each exposure and death from natural, cardiovascular (CVD) or non-malignant respiratory disease. Analyses included single and two exposure models, and subset analysis to study lower exposure ranges.

Results
During follow-up, 661,534 individuals died of natural causes (36.6% CVD, 6.6% respiratory). All exposures including the PM2.5 components were associated with natural mortality, with hazard ratios (95% confidence intervals) of 1.026 (1.015, 1.038) per 5 µg/m3 PM2.5, 1.050 (1.041, 1.059) per 10 µg/m3 NO2, 1.057 (1.048, 1.067) per 0.5 × 10–5/m BC and 1.045 (1.040, 1.049) per 10 dB Lden total transportation noise. NO2, BC, Cu, Fe and noise were consistently associated with CVD and respiratory mortality, whereas PM2.5 was only associated with CVD mortality. Natural mortality associations persisted < 20 µg/m3 for PM2.5 and NO2, < 1.5 10–5/m BC and < 53 dB Lden total transportation noise. The O3 association was inverse for all outcomes. Including noise attenuated all outcome associations, though many remained significant. Across outcomes, noise was robust to adjustment to air pollutants (e.g. natural mortality 1.037 (1.033, 1.042) per 10 dB Lden total transportation noise, after including BC).

Conclusion
Long-term exposure to air pollution and transportation noise in Switzerland contribute to premature mortality. Considering co-exposures revealed the importance of local traffic-related pollutants such as NO2, BC and transportation noise.
Anti-CHAC1 exosomes for nose-to-brain delivery of miR-760-3p in cerebral ischemia/reperfusion injury mice inhibiting neuron ferroptosis
Authors: Wang Yong , Niu Huicong , Li Luyu , Han Jing , Liu Zhuohang , Chu Min , Sha Xianyi , Zhao Jing 
Published: March 2023

AbstractFerroptosis plays a critical role in ischemic stroke, and anti-ferroptosis strategies were regarded as potentially effective measures. Based on ferroptosis-related mechanisms, this study aims to design and prepare anti-ferroptosis exosomes from adipose-derived mesenchymal stem cells (ADSC-Exo) for treating ischemic brain injury via intranasal (IN) administration. According to the bioinformatic analysis, CHAC1 was a key gene in the progress of ferroptosis in ischemic stroke. miR-760-3p can inhibit the expression of CHAC1 and may be abundant in ADSC-Exo. Therefore, ADSC-Exo were successfully isolated and the immunofluorescence showed that they can be efficiently delivered to the brain via IN administration. Additionally, IN administration of ADSC-Exo can effectively improve the neurobehavior function of mice after I/R, and improve the ferroptosis-related outcomes. As the immunofluorescence showed the co-localization of NeuN with CHAC1 obviously, we further evaluated the systematic effect of ADSC-Exo in an oxygen–glucose deprivation (OGD) mouse neuroblastoma cell line N2a model. The results showed that miR-760-3p in ADSC‐Exo contributed to their function in inhibiting ferroptosis by targeting CHAC1 in neurons. Collectively, the present study successfully designed and prepared anti-CHAC1 ADSC-Exo and suggested a promising exosome-based strategy for anti-ferroptosis therapy in cerebral ischemia/reperfusion injury.
Graphical abstract