bluuebunny/crossref_metadata_2025_split huggingface dataset:
An analysis of past and future heatwaves based on a heat-associated mortality threshold: towards a heat health warning system
Authors: Kapwata Thandi , Gebreslasie Michael T. , Wright Caradee Y. 
Published: November 2022

AbstractHeatwaves can have severe impacts on human health extending from illness to mortality. These health effects are related to not only the physical phenomenon of heat itself but other characteristics such as frequency, intensity, and duration of heatwaves. Therefore, understanding heatwave characteristics is a crucial step in the development of heat-health warning systems (HHWS) that could prevent or reduce negative heat-related health outcomes. However, there are no South African studies that have quantified heatwaves with a threshold that incorporated a temperature metric based on a health outcome. To fill this gap, this study aimed to assess the spatial and temporal distribution and frequency of past (2014 – 2019) and future (period 2020 – 2039) heatwaves across South Africa. Heatwaves were defined using a threshold for diurnal temperature range (DTR) that was found to have measurable impacts on mortality. In the current climate, inland provinces experienced fewer heatwaves of longer duration and greater intensity compared to coastal provinces that experienced heatwaves of lower intensity. The highest frequency of heatwaves occurred during the austral summer accounting for a total of 150 events out of 270 from 2014 to 2019. The heatwave definition applied in this study also identified severe heatwaves across the country during late 2015 to early 2016 which was during the strongest El Niño event ever recorded to date. Record-breaking global temperatures were reported during this period; the North West province in South Africa was the worst affected experiencing heatwaves ranging from 12 to 77 days. Future climate analysis showed increasing trends in heatwave events with the greatest increases (80%—87%) expected to occur during summer months. The number of heatwaves occurring in cooler seasons is expected to increase with more events projected from the winter months of July and August, onwards. The findings of this study show that the identification of provinces and towns that experience intense, long-lasting heatwaves is crucial to inform development and implementation of targeted heat-health adaptation strategies. These findings could also guide authorities to prioritise vulnerable population groups such as the elderly and children living in high-risk areas likely to be affected by heatwaves.
Bone mass density following developmental exposures to perfluoroalkyl substances (PFAS): a longitudinal cohort study
Authors: Blomberg Annelise , Mortensen Jann , Weihe Pál , Grandjean Philippe 
Published: November 2022

Abstract
Background
Environmental exposures to industrial chemicals, including perfluoroalkyl substances (PFAS), may play a role in bone development and future risk of osteoporosis. However, as prospective evidence is limited, the role of developmental PFAS exposures in bone density changes in childhood is unclear. The objective of this study was to estimate associations between serum-PFAS concentrations measured in infancy and early childhood and areal bone mineral density (aBMD) measured at age 9 years in a birth cohort of children from the Faroe Islands.

Methods
We prospectively measured concentrations of five PFAS in cord serum and serum collected at 18 months, 5 years and 9 years, and conducted whole-body DXA scans at the 9-year clinical visit. Our study included 366 mother-child pairs with DXA scans and at least one PFAS measurement. We estimated covariate-adjusted associations of individual PFAS concentrations with age-, sex- and height-adjusted aBMD z-scores using multivariable regression models and applied formal mediation analysis to estimate the possible impact of by several measures of body composition. We also evaluated whether associations were modified by child sex.

Results
We found PFAS exposures in childhood to be negatively associated with aBMD z-scores, with the strongest association seen for perfluorononanoic acid (PFNA) at age 5 years. A doubling in age-5 PFNA was associated with a 0.15 decrease in aBMD z-score (95% CI: − 0.26, − 0.039). The PFNA-aBMD association was significantly stronger in males than females, although effect modification by sex was not significant for other PFAS exposures. Results from the mediation analysis suggested that any potential associations between aBMD and 18-month PFAS concentrations may be mediated by total body fat and BMI, although most estimated total effects for PFAS exposures at age 18 months were non-significant. PFAS exposures at age 9 were not associated with age-9 aBMD z-scores.

Conclusions
The PFAS-aBMD associations identified in this and previous studies suggest that bone may be a target tissue for PFAS. Pediatric bone density has been demonstrated to strongly track through young adulthood and possibly beyond; therefore, these prospective results may have important public health implications.
Using non-parametric Bayes shrinkage to assess relationships between multiple environmental and social stressors and neonatal size and body composition in the Healthy Start cohort
Authors: Martenies Sheena E. , Hoskovec Lauren , Wilson Ander , Moore Brianna F. , Starling Anne P. , Allshouse William B. , Adgate John L. , Dabelea Dana , Magzamen Sheryl 
Published: November 2022

AbstractBackgroundBoth environmental and social factors have been linked to birth weight and adiposity at birth, but few studies consider the effects of exposure mixtures. Our objective was to identify which components of a mixture of neighborhood-level environmental and social exposures were driving associations with birth weight and adiposity at birth in the Healthy Start cohort.MethodsExposures were assessed at the census tract level and included air pollution, built environment characteristics, and socioeconomic status. Prenatal exposures were assigned based on address at enrollment. Birth weight was measured at delivery and adiposity was measured using air displacement plethysmography within three days. We used non-parametric Bayes shrinkage (NPB) to identify exposures that were associated with our outcomes of interest. NPB models were compared to single-predictor linear regression. We also included generalized additive models (GAM) to assess nonlinear relationships. All regression models were adjusted for individual-level covariates, including maternal age, pre-pregnancy BMI, and smoking.ResultsResults from NPB models showed most exposures were negatively associated with birth weight, though credible intervals were wide and generally contained zero. However, the NPB model identified an interaction between ozone and temperature on birth weight, and the GAM suggested potential non-linear relationships. For associations between ozone or temperature with birth weight, we observed effect modification by maternal race/ethnicity, where effects were stronger for mothers who identified as a race or ethnicity other than non-Hispanic White. No associations with adiposity at birth were observed.ConclusionsNPB identified prenatal exposures to ozone and temperature as predictors of birth weight, and mothers who identify as a race or ethnicity other than non-Hispanic White might be disproportionately impacted. However, NPB models may have limited applicability when non-linear effects are present. Future work should consider a two-stage approach where NPB is used to reduce dimensionality and alternative approaches examine non-linear effects.
The clinical outcomes of high neutralizing antibodies titer convalescent plasma therapy in early developed severe COVID-19 patients; a case–control study
Authors: Nontawong Nuttakant , Siripongboonsitti Taweegrit , Tawinprai Kriangkrai , Boonpratoom Mana , Krailassiri Nawin , Boonkhum Chayaporn , Soonklang Kamonwan , Poovorawan Yong , Mahanonda Nithi 
Published: November 2022

Abstract
Background
Coronavirus disease 2019 (COVID-19) causes life-threatening pneumonia. Convalescent plasma therapy (CPT) is expected to be the effective COVID-19 treatment for passive immunity. The high neutralizing antibodies titer of CPT is needed to prove the benefit in early developed severe COVID-19.

Objective
This case–control study evaluated transfusion efficacy and adverse events with high-titer (≥ 1:320) COVID-19 convalescent plasma compared with standard care alone in severe COVID-19 pneumonia.

Results
Among 107 severe COVID-19 patients, 55 received CPT plus standard care, and 52 received standard care alone. All-cause mortality was 15.3% in the CPT group compared with 85.4% in the standard care group (p < 0.001). Univariate and multivariate analyses revealed reduced mortality with CPT (HR 0.14; 95% CI 0.07–0.31; p < 0.001 and HR 0.26; 95% CI 0.08–0.79; p = 0.018, respectively). CPT resulted in decreased use of mechanical ventilation, duration of supplemental oxygen, and high-flow oxygen requirement. Clinical and radiological outcomes improved.

Conclusions
Immediate high neutralizing antibody titer CPT is safe and reduces mortality in early developed severe COVID-19 patients. The benefit of CPT in the early course of illness is challenging and requires additional study.
Trial registration Thai clinical trials registry (TCTR) no. 20220101003.
Uterine macrophages as treatment targets for therapy of premature rupture of membranes by modified ADSC-EVs through a circRNA/miRNA/NF-κB pathway
Authors: Gao Yuhua , Mi Ningning , Zhang Ying , Li Xiangchen , Guan Weijun , Bai Chunyu 
Published: November 2022

AbstractBackgroundCircular RNA (circRNA) is a type of stable non-coding RNA that modifies macrophage inflammation by sponging micro RNAs (miRNAs), binding to RNA-binding proteins, and undergoing translation into peptides. Activated M1 phenotype macrophages secrete matrix metalloproteinases to participate in softening of the cervix uteri to promote vaginal delivery.MethodsIn this study, the premature rupture of membranes (PROM) mouse model was used to analyze the role of macrophages in this process. Profiling of circRNAs was performed using a competing endogenous RNA microarray, and their functions were elucidated in vitro. Meanwhile, adipose tissue-derived stem cell-secreted extracellular vesicles (EVs) were applied as a vehicle to transport small interfering RNAs (siRNAs) targeting the circRNAs to demonstrate their biological function in vivo.ResultsThe miRNAmiR-1931is dependent on the nuclear factor kappa-B (NF-κB) pathway but negatively regulates its activation by targeting the NF-κB signaling transducer TRAF6 to prevent polarization of M1 macrophages and inhibit matrix metalloproteinase (MMP) secretion. The host gene of circRNAB4GALNT1, also an NF-κB pathway-dependent gene, circularizes to formcircRNA_0002047, which spongesmiR-1931to maintain NF-κB pathway activation and MMP secretion in vitro. In the PROM model, EVs loaded with siRNAs targeting circRNAs demonstrated that the circRNAs reducedmiR-1931expression to maintain NF-κB pathway activation and MMP secretion for accelerating PROM in vivo.ConclusionsOur data provide insights into understanding PROM pathogenesis and improving PROM treatment.
Melanin-like nanoparticles: advances in surface modification and tumour photothermal therapy
Authors: Tian Luyao , Li Xia , Ji Haixia , Yu Qing , Yang Mingjuan , Guo Lanping , Huang Luqi , Gao Wenyuan 
Published: November 2022

AbstractCurrently, tumor treatments are characterized by intelligence, diversity and personalization, but the therapeutic reagents used are often limited in clinical efficacy due to problems with water solubility, targeting, stability and multidrug resistance. To remedy these shortcomings, the application of multifunctional nanotechnology in the biomedical field has been widely studied. Synthetic melanin nanoparticles (MNPs) surfaces which contain highly reactive chemical groups such as carboxyl, hydroxyl and amine groups, can be used as a reaction platform on which to graft different functional components. In addition, MNPs easily adhere to substrate surface, and serve as a secondary reaction platform to modify it. The multifunctionality and intrinsic biocompatibility make melanin-like nanoparticles promising as a multifunctional and powerful nanoplatform for oncological applications. This paper first reviews the preparation methods, polymerization mechanisms and physicochemical properties of melanin including natural melanin and chemically synthesized melanin to guide scholars in MNP-based design. Then, recent advances in MNPs especially synthetic polydopamine (PDA) melanin for various medical oncological applications are systematically and thoroughly described, mainly focusing on bioimaging, photothermal therapy (PTT), and drug delivery for tumor therapy. Finally, based on the investigated literature, the current challenges and future directions for clinical translation are reasonably discussed, focusing on the innovative design of MNPs and further elucidation of pharmacokinetics. This paper is a timely and comprehensive and detailed study of the progress of MNPs in tumor therapy, especially PTT, and provides ideas for the design of personalized and customizable oncology nanomedicines to address the heterogeneity of the tumor microenvironment.
Graphical Abstract
Attitudes toward harm reduction and low-threshold healthcare during the COVID-19 pandemic: qualitative interviews with people who use drugs in rural southern Illinois
Authors: Rains Alex , York Mary , Bolinski Rebecca , Ezell Jerel , Ouellet Lawrence J. , Jenkins Wiley D. , Pho Mai T. 
Published: November 2022

Abstract
Background
Chronic health conditions associated with long-term drug use may pose additional risks to people who use drugs (PWUD) when coupled with COVID-19 infection. Despite this, PWUD, especially those living in rural areas, may be less likely to seek out health services. Previous research has highlighted the increased disease burden of COVID-19 among PWUD. Our manuscript supplements this literature by exploring unique attitudes of PWUD living in rural areas toward the pandemic, COVID-19 vaccination, and the role of harm reduction (HR) organizations in raising health awareness among PWUD.

Methods
Semi-structured interviews were conducted with 20 PWUD living in rural southern Illinois. Audio recordings were professionally transcribed. A preliminary codebook was created based on interview domains. Two trained coders conducted iterative coding of the transcripts, and new codes were added through line-by-line coding and thematic grouping.

Results
Twenty participants (45% female, mean age of 38) completed interviews between June and November 2021. Participants reported negative impacts of the pandemic on mental health, financial wellbeing, and drug quality. However, the health impacts of COVID-19 were often described as less concerning than its impacts on these other aspects of life. Many expressed doubt in the severity of COVID-19 infection. Among the 16 unvaccinated participants who reported receiving most of their information from the internet or word of mouth, uncertainty about vaccine contents and distrust of healthcare and government institutions engendered wariness of the vaccination. Distrust of healthcare providers was related to past stigmatization and judgement, but did not extend to the local HR organization, which was unanimously endorsed as a positive institution. Among participants who did not access services directly from the HR organization, secondary distribution of HR supplies by other PWUD was a universally cited form of health maintenance. Participants expressed interest in low-threshold healthcare, including COVID-19 vaccination, should it be offered in the local HR organization’s office and mobile units.

Conclusion
COVID-19 and related public health measures have affected this community in numerous ways. Integrating healthcare services into harm reduction infrastructures and mobilizing secondary distributors of supplies may promote greater engagement with vaccination programs and other healthcare services.

Trial number

NCT04427202.
The long noncoding RNA TARID regulates the CXCL3/ERK/MAPK pathway in trophoblasts and is associated with preeclampsia
Authors: Liao Lingyun , Liu Min , Gao Yijie , Wei Xiaohong , Yin Yangxue , Gao Linbo , Zhou Rong 
Published: November 2022

Abstract
Background
The widely accepted explanation of preeclampsia (PE) pathogenesis is insufficient trophoblast invasion and impaired uterine spiral artery remodeling. However, the underlying molecular mechanism remains unclear.

Methods
We performed transcriptome sequencing on placentas of normal and PE patients and identified 976 differentially expressed long noncoding RNAs (lncRNAs). TCF21 antisense RNA inducing demethylation (TARID) was one of the most significantly differentially expressed lncRNAs and was negatively correlated with the systolic and diastolic blood pressure in PE patients. Furthermore, we verified the effect of TARID on the biological behavior of trophoblasts and performed UID mRNA-seq to identify the effectors downstream of TARID. Then, co-transfection experiments were used to better illustrate the interaction between TARID and its downstream effector.

Results
We concluded that the downregulation of TARID expression may inhibit trophoblast infiltration and spiral artery remodeling through inhibition of cell migration, invasion, and tube formation mediated through the CXCL3/ERK/MAPK pathway.

Conclusions
Overall, these findings suggested that TARID may be a therapeutic target for PE through the CXCL3/ERK/MAPK pathway.
Peripheral myeloid-derived suppressor cells are good biomarkers of the efficacy of fingolimod in multiple sclerosis
Authors: Camacho-Toledano Celia , Machín-Díaz Isabel , Calahorra Leticia , Cabañas-Cotillas María , Otaegui David , Castillo-Triviño Tamara , Villar Luisa María , Costa-Frossard Lucienne , Comabella Manuel , Midaglia Luciana , García-Domínguez José Manuel , García-Arocha Jennifer , Ortega María Cristina , Clemente Diego 
Published: November 2022

Abstract
Background
The increasing number of treatments that are now available to manage patients with multiple sclerosis (MS) highlights the need to develop biomarkers that can be used within the framework of individualized medicine. Fingolimod is a disease-modifying treatment that belongs to the sphingosine-1-phosphate receptor modulators. In addition to inhibiting T cell egress from lymph nodes, fingolimod promotes the immunosuppressive activity of myeloid-derived suppressor cells (MDSCs), whose monocytic subset (M-MDSCs) can be used as a biomarker of disease severity, as well as the degree of demyelination and extent of axonal damage in the experimental autoimmune encephalomyelitis (EAE) model of MS. In the present study, we have assessed whether the abundance of circulating M-MDSCs may represent a useful biomarker of fingolimod efficacy in EAE and in the clinical context of MS patients.

Methods
Treatment with vehicle or fingolimod was orally administered to EAE mice for 14 days in an individualized manner, starting the day when each mouse began to develop clinical signs. Peripheral blood from EAE mice was collected previous to treatment and human peripheral blood mononuclear cells (PBMCs) were collected from fingolimod to treat MS patients’ peripheral blood. In both cases, M-MDSCs abundance was analyzed by flow cytometry and its relationship with the future clinical affectation of each individual animal or patient was assessed.

Results
Fingolimod-treated animals presented a milder EAE course with less demyelination and axonal damage, although a few animals did not respond well to treatment and they invariably had fewer M-MDSCs prior to initiating the treatment. Remarkably, M-MDSC abundance was also found to be an important and specific parameter to distinguish EAE mice prone to better fingolimod efficacy. Finally, in a translational effort, M-MDSCs were quantified in MS patients at baseline and correlated with different clinical parameters after 12 months of fingolimod treatment. M-MDSCs at baseline were highly representative of a good therapeutic response to fingolimod, i.e., patients who met at least two of the criteria used to define non-evidence of disease activity-3 (NEDA-3) 12 months after treatment.

Conclusion
Our data indicate that M-MDSCs might be a useful predictive biomarker of the response of MS patients to fingolimod.
Preimplantation genetic testing for familial amyloid polyneuropathy
Authors: Sousa Mário 
Published: November 2022

Abstract
Background
Embryo selection in Familial amyloid polyneuropathy eradicates the disease, but the widespread application of preimplantation genetic testing (PGT) for this monogenic disease still requires greater political and clinical commitment.

Main body
Familial amyloid polyneuropathy is a fatal, chronic, hereditary autosomal dominant neurodegenerative disorder caused by a single nucleotide mutation in the transthyretin gene. The disease courses with infertility, cachexia, blindness, renal failure, cardiovascular collapse, and premature death. Treatments include organ transplantation, transthyretin stabilizers, silencers and gene editing. Unfortunately, these treatments only improve the patient’s quality of life.

Short conclusion
The application of PGT would prevent the disease, the birth of children with this devastating disease and the enormous health costs associated. For PGT to become the first reproductive option for patients, a paradigm shift in governmental, social and medical policies is necessary.
The advancement of a gender ethics protocol to uncover gender ethical dilemmas in midwifery: a preliminary theory model
Authors: Christianson Monica , Lehn Sine , Velandia Marianne 
Published: November 2022

Abstract
Objectives
Ethical dilemmas at both the individual and structural level are part of the daily work of midwives and gender inequality and injustice can affect women’s sexual and reproductive health. Mainstream bioethical theory has been criticized for neglecting women’s issues. To ensure women’s experiences are addressed, a gender lens on ethics is crucial.

Aim
This study develops a theory model by exploring ethical dilemmas related to gender in the context of maternity care from the perspective of midwifery science and feminist ethics.

Methods
The research strategy followed a coherent stepwise approach: literature search, thematic analysis, elaboration of a gender ethics protocol, and the integration of various components into a preliminary gender ethics model for midwifery.

Findings
A literature search was performed using Scopus and Web of Science to identify ethical dilemmas in maternity care linked to gender and power. The search of articles published between 1996 and 2019 returned 61 abstracts. These abstracts were screened and assigned one of the following themes: The Midwifery Profession, The Rights of the Woman, Fetal Rights Dominate, and Medicalization of Pregnancy and Childbirth. A tentative gender ethics frame was developed and tested on two articles on abortion, one from Denmark and one from Japan. The protocol facilitated the gender analysis of ethical dilemmas related to abortion, which were related to the imbalance of power relations in health care. In the final step, we synthesized the dimensions of gender and power in a gender ethics model for midwifery.

Discussion
The gender ethics protocol developed revealed gendered dimensions of ethical dilemmas in midwifery. This gender analysis adds to the understanding of the “do no harm” principle by revealing assumptions and stereotypes that promote unequal power relations. The gender ethics model is an innovative approach that envisions and exposes power imbalance at the micro, meso, and macro levels.

Conclusions
The protocol could improve gender competence among researchers, midwives/professionals, and midwifery students throughout the world.