bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated proteomics and metabolomics analysis of lumbar in a rat model of osteoporosis treated with Gushukang capsules
Authors: Lin Ruohui , Xie Bingying , Xie Lihua , Ge Jirong , Li Shengqiang 
Published: December 2022

Abstract
Background
Gushukang (GSK) capsules are a Chinese patented medicine that is widely used in clinics for the treatment of osteoporosis (OP). Animal experiments have revealed that the bone mineral density of osteoporotic rats increase after treatment with GSK capsules. However, the specific mechanism and target of GSK in the treatment of osteoporosis are unclear. Further studies are needed.

Methods
Metabolomics (GC/MS) and proteomics (TMT-LC-MC/MC) with bioinformatics (KEGG pathway enrichment), correlation analysis (Pearson correlation matrix), and joint pathway analysis (MetaboAnalyst) were employed to determine the underlying mechanisms of GSK. The differential expression proteins were verified by WB experiment.

Results
The regulation of proteins, i.e., Cant1, Gstz1, Aldh3b1, Bid, and Slc1a3, in the common metabolic pathway of differential proteins and metabolites between GSK/OP and OP/SHAM was corrected in the GSK group. The regulation of 12 metabolites (tyramine, thymidine, deoxycytidine, cytosine, L-Aspartate, etc.) were differential in the common enrichment metabolic pathway between GSK /OP and OP/SHAM. Differential proteins and metabolites jointly regulate 11 metabolic pathways, such as purine metabolism, pyrimidine metabolism, histidine metabolism, beta-alanine metabolism, and so on.

Conclusion
GSK may protect bone metabolism in osteoporotic rats by affecting nucleotide metabolism, amino acid metabolism, and the immune system.
Peer mentorship to build research capacity among members of the International Student Surgical Network (InciSioN): a proof of concept study
Authors: Kanmounye Ulrick Sidney , Bandyopadhyay Soham , Munoz-Valencia Alejandro , Khalil Halimah , Sana Hamaiyal , Badwi Nermin , Ma Xiya , Swaroop Mamta , Madani Katayoun 
Published: December 2022

Abstract
Background
International Student Surgical Network (InciSioN) is the largest student and trainee global surgery interest group worldwide and its members have contributed significantly to global surgery research. The InciSioN Research Capacity-Building (IReCaB) program aimed to enhance the research skills and confidence of participants via a peer mentorship model.

Methods
After an open call to members of InciSioN to enroll, participants’ knowledge of research methods and the process was evaluated through a test to assign mentor and mentee roles, with mentors being those who scored ≥ 20/25. Mentors then delivered a series of four webinars to help disseminate research methodology to mentees. Finally, mentees were tested on their knowledge of research and their satisfaction with the program was also evaluated.

Results
Fifty-two participants, mostly from LMICs (n = 23/52, 44.2%) were enrolled, and 36 completed the program. There was a significant improvement in the proportion of questions answered correctly on the post-program test (R = 0.755, p < 0.001). Post-IReCaB test scores were greater than pre-IReCaB scores (p < 0.001). The difference in confidence after the course was also significant (p < 0.001). IReCaB participants successfully designed, implemented, and published an international cross-sectional study.

Conclusion
This study showed improvements in participants’ understanding of theoretical components of scientific research. We offer a model for research capacity building that can be implemented, modeled, and further refined by similar organizations with academic research goals.
Patient allocation method in major epidemics under the situation of hierarchical diagnosis and treatment
Authors: Ye Yong , Huang Lizhen , Wang Jie , Chuang Yen-Ching , Pan Lingle 
Published: December 2022

AbstractObjectivesPatients are classified according to the severity of their condition and graded according to the diagnosis and treatment capacity of medical institutions. This study aims to correctly assign patients to medical institutions for treatment and develop patient allocation and medical resource expansion schemes among hospitals in the medical network.MethodsIllness severity, hospital level, allocation matching benefit, distance traveled, and emergency medical resource fairness were considered. A multi-objective planning method was used to construct a patient allocation model during major epidemics. A simulation study was carried out in two scenarios to test the proposed method.Results(1) The single-objective model obtains an unbalanced solution in contrast to the multi-objective model. The proposed model considers multi-objective problems and balances the degree of patient allocation matching, distance traveled, and fairness. (2) The non-hierarchical model has crowded resources, and the hierarchical model assigns patients to matched medical institutions. (3) In the “demand exceeds supply” situation, the patient allocation model identified additional resources needed by each hospital.ConclusionResults verify the maneuverability and effectiveness of the proposed model. It can generate schemes for specific patient allocation and medical resource amplification and can serve as a quantitative decision-making tool in the context of major epidemics.
Male and female mice display consistent lifelong ability to address potential life-threatening cues using different post-threat coping strategies
Authors: Liu Xue , Feng Xiaolong , Huang Hongren , Huang Kang , Xu Yang , Ye Shuwei , Tseng Yu-Ting , Wei Pengfei , Wang Liping , Wang Feng 
Published: December 2022

Abstract
Background
Sex differences ranging from physiological functions to pathological disorders are developmentally hard-wired in a broad range of animals, from invertebrates to humans. These differences ensure that animals can display appropriate behaviors under a variety of circumstances, such as aggression, hunting, sleep, mating, and parental care, which are often thought to be important in the acquisition of resources, including territory, food, and mates. Although there are reports of an absence of sexual dimorphism in the context of innate fear, the question of whether there is sexual dimorphism of innate defensive behavior is still an open question. Therefore, an in-depth investigation to determine whether there are sex differences in developmentally hard-wired innate defensive behaviors in life-threatening circumstances is warranted.

Results
We found that innate defensive behavioral responses to potentially life-threatening stimuli between males and females were indistinguishable over their lifespan. However, by using 3 dimensional (3D)-motion learning framework analysis, we found that males and females showed different behavioral patterns after escaping to the refuge. Specifically, the defensive “freezing” occurred primarily in males, whereas females were more likely to return directly to exploration. Moreover, there were also no estrous phase differences in innate defensive behavioral responses after looming stimuli.

Conclusions
Our results demonstrate that visually-evoked innate fear behavior is highly conserved throughout the lifespan in both males and females, while specific post-threat coping strategies depend on sex. These findings indicate that innate fear behavior is essential to both sexes and as such, there are no evolutionary-driven sex differences in defensive ability.
Use of hormonal contraceptives and antidepressants and risks of suicidal behavior and accidents among women with premenstrual disorders: a nationwide cohort study
Authors: Yang Qian , Lagerberg Tyra , Sjölander Arvid , Bertone-Johnson Elizabeth R. , Fang Fang , Ye Weimin , Chang Zheng , Valdimarsdóttir Unnur A. , Lu Donghao 
Published: December 2022

AbstractBackgroundWomen with premenstrual disorders (PMDs) are at increased risks of suicidal behavior and accidents. However, the effect of PMD first-line treatment on such risks have not been assessed.MethodsTo study the association between use of hormonal contraceptives or antidepressants and subsequent risks of suicidal behavior and accidents among women with PMDs. We conducted a nationwide register-based cohort study with between- and within-individual analyses in Sweden. All women with a clinical diagnosis/indication of PMDs recorded in the Patient Register and the Prescribed Drug Register during 1987–2011 were included (n = 23 029, age 15–52 years). Information on hormonal contraceptives and antidepressants prescribed for these women was obtained from the Prescribed Drug Register. Events of suicidal behavior (complete suicide and suicide attempt) and accidents were separately identified through the Patient and the Causes of Death Registers. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of suicidal behavior and accidents after use of hormonal contraceptives or antidepressants were estimated in between-individual and within-individual analyses (i.e., comparing the risk between use and no use in the same individual) using Poisson regression.ResultsWomen with PMDs were followed for a median of 6.2 years. Compared to no use of hormonal contraceptives, use of hormonal contraceptives was associated with a lower risk of suicidal behavior in both between-individual (IRR 0.76, 0.43–1.34) and within-individual analyses (IRR 0.65, 0.51–0.83). These risk reductions were primarily restricted to combined products (IRR 0.18, 0.07–0.47 and 0.19, 0.08–0.42 in between- and within-individual analyses) and observed among women with/without psychiatric comorbidities (pfor interaction 0.830 and 0.043 in between- and within-individual analyses). Yet, the use of hormonal contraceptives was not consistently associated with risk of accidents between between-individual (IRR 1.13, 1.01–1.27) and within-individual analyses (IRR 1.01, 0.92–1.11). Use of antidepressants was associated with a higher risk of suicidal behavior and accidents in both between- and within-individual analyses.ConclusionsOur findings suggest that use of hormonal contraceptives, particularly combined products, is associated with reduced rates of suicidal behaviors, but not accidents, among women with PMDs. The estimates for antidepressants may be biased by indication.
An electrochemical nitric oxide generator for in-home inhalation therapy in pulmonary artery hypertension
Authors: Liu Yiwei , Zhu Yifan , Jiang Chenyu , Su Zhanhao , Yan Yi , Feng Bei , Mao Wen , Zhang Yuyan , Wang Xiaojian , Xu Zhuoming , Zhang Hao 
Published: December 2022

Abstract
Background
Inhaled NO is a selective pulmonary vasodilator proven to be therapeutic for patients with pulmonary artery hypertension (PAH). The most common NO delivery system in clinical practice is cylinder-based, but unfortunately limited by its high costs, complicated delivery, and the requirement of an extensive supply chain, leaving vast unmet medical needs globally.

Methods
To address the need for rapid, affordable, and safe production of nitric oxide (NO) for in-home inhalation therapy in patients with PAH. We developed a novel portable device to derive NO from a nitrite complex solution with a copper(II)-ligand catalyst, and further examined its effectiveness in a porcine model of PAH. This model was established by using female Bama miniature pig and induced by monocrotaline (MCT) administration.

Results
This generator could rapidly and safely produce therapeutic NO at concentrations ranging from 0 to 100 parts per million (ppm) with the least disproportionated nitrogen dioxide (NO2) and byproducts. It could effectively alleviate pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in piglets with PAH, without causing major physiologic disruptions.

Conclusions
Our electrochemical NO generator is able to produce the desired NO doses for pulmonary vasodilation in a safe and sustainable way, with low costs, which paves the way for its subsequent clinical trials in the patient with PAH and other common cardiopulmonary conditions with a high disease burden around the world.
Dynamic feedback regulation for efficient membrane protein production using a small RNA-based genetic circuit in Escherichia coli
Authors: Guidi Chiara , De Wannemaeker Lien , De Baets Jasmine , Demeester Wouter , Maertens Jo , De Paepe Brecht , De Mey Marjan 
Published: December 2022

Abstract
Background
Membrane proteins (MPs) are an important class of molecules with a wide array of cellular functions and are part of many metabolic pathways. Despite their great potential—as therapeutic drug targets or in microbial cell factory optimization—many challenges remain for efficient and functional expression in a host such as Escherichia coli.

Results
A dynamically regulated small RNA-based circuit was developed to counter membrane stress caused by overexpression of different MPs. The best performing small RNAs were able to enhance the maximum specific growth rate with 123%. On culture level, the total MP production was increased two-to three-fold compared to a system without dynamic control. This strategy not only improved cell growth and production of the studied MPs, it also suggested the potential use for countering metabolic burden in general.

Conclusions
A dynamically regulated feedback circuit was developed that can sense metabolic stress caused by, in casu, the overexpression of an MP and responds to it by balancing the metabolic state of the cell and more specifically by downregulating the expression of the MP of interest. This negative feedback mechanism was established by implementing and optimizing simple-to-use genetic control elements based on post-transcriptional regulation: small non-coding RNAs. In addition to membrane-related stress when the MP accumulated in the cytoplasm as aggregates, the sRNA-based feedback control system was still effective for improving cell growth but resulted in a decreased total protein production. This result suggests promiscuity of the MP sensor for more than solely membrane stress.
Low genetic diversity of Plasmodium falciparum merozoite surface protein 1 and 2 and multiplicity of infections in western Ethiopia following effective malaria interventions
Authors: Tadele Geletta , Jaiteh Fatou K. , Oboh Mary , Oriero Eniyou , Dugassa Sisay , Amambua-Ngwa Alfred , Golassa Lemu 
Published: December 2022

AbstractBackgroundGenetic diversity of malaria parasites can inform the intensity of transmission and poses a major threat to malaria control and elimination interventions. Characterization of the genetic diversity would provide essential information about the ongoing control efforts. This study aimed to explore allelic polymorphism of merozoite surface protein 1 (msp1) and merozoite surface protein 2 (msp2) to determine the genetic diversity and multiplicity ofPlasmodium falciparuminfections circulating in high and low transmission sites in western Ethiopia.MethodsParasite genomic DNA was extracted from a total of 225 dried blood spots collected from confirmed uncomplicatedP. falciparummalaria-infected patients in western Ethiopia. Of these, 72.4% (163/225) and 27.6% (62/225) of the samples were collected in high and low transmission areas, respectively. Polymorphicmsp1andmsp2genes were used to explore the genetic diversity and multiplicity of falciparum malaria infections. Genotyping ofmsp1was successful in 86.5% (141/163) and 88.7% (55/62) samples collected from high and low transmission areas, respectively. Genotyping ofmsp2was carried out among 85.3% (139/163) and 96.8% (60/62) of the samples collected in high and low transmission sites, respectively.Plasmodium falciparum msp1andmsp2genes were amplified by nested PCR and the PCR products were analysed by QIAxcel ScreenGel Software. A P-value of less or equal to 0.05 was considered significant.ResultsHigh prevalence of falciparum malaria was identified in children less than 15 years as compared with those  ≥ 15 years old (AOR = 2.438, P = 0.005). The three allelic families ofmsp1(K1, MAD20, and RO33) and the two allelic families ofmsp2(FC27 and 3D7), were observed in samples collected in high and low transmission areas. However, MAD 20 and FC 27 alleles were the predominant allelic families in both settings.Plasmodium falciparumisolates circulating in western Ethiopia had low genetic diversity and mean MOI. No difference in mean MOI between high transmission sites (mean MOI 1.104) compared with low transmission area (mean MOI 1.08) (p > 0.05). The expected heterozygosity ofmsp1was slightly higher in isolates collected from high transmission sites (He = 0.17) than in those isolates from low transmission (He = 0.12). However, the heterozygosity ofmsp2 was not different in both settings (Pfmsp2: 0.04 in high transmission; pfmsp2: 0.03 in low transmission).ConclusionPlasmodium falciparumfrom clinical malaria cases in western Ethiopia has low genetic diversity and multiplicity of infection irrespective of the intensity of transmission at the site of sampling. These may be signaling the effectiveness of malaria control strategies in Ethiopia; although further studies are required to determine how specific intervention strategies and other parameters that drive the pattern.
Unaffordability of COVID-19 tests: assessing age-related inequalities in 83 countries
Authors: Flores Gabriela , Abbasi Asiyeh , Korachais Catherine , Lavado Rouselle 
Published: December 2022

Abstract
Background
Diagnostic testing for SARS-CoV-2 is critical to manage the pandemic and its different waves. The requirement to pay out-of-pocket (OOP) for testing potentially represents both a financial barrier to access and, for those who manage to make the payment, a source of financial hardship, as they may be forced to reduce spending on other necessities. This study aims to assess age-related inequality in affordability of COVID-19 tests.

Methods
Daily data from the Global COVID-19 Trends and Impact Survey among adult respondents across 83 countries from July 2020 to April 2021 was used to monitor age-related inequalities across three indicators: the experiences of, first, reducing spending on necessities because of paying OOP for testing, second, facing financial barriers to get tested (from January to April 2021), and third, having anxiety related to household finance in the future. Logistic regressions were used to assess the association of age with each of these.

Results
Among the population ever tested, the adjusted odds of reducing spending on necessities due to the cost of the test decreased non-linearly with age from 2.3 [CI95%: 2.1–2.5] among ages 18–24 to 1.6 [CI95%: 1.5–1.8] among ages 45–54. Among the population never tested, odds of facing any type of barrier to testing were highest among the youngest age group 2.5 [CI95%:2.4–2.5] and decreased with age. Finally, among those reporting reducing spending on necessities, the odds of reporting anxiety about their future finances decreased non-linearly with age, with the two younger groups being 2.4–2.5 times more anxious than the oldest age group. Among those reporting financial barriers due to COVID-19 test cost, there was an inverse U-shape relationship.

Conclusions
COVID-19 testing was associated with a reduction in spending on necessities at varying levels by age. Younger people were more likely to face financial barrier to get tested. Both negative outcomes generated anxiety across all age-groups but more frequently among the younger ones. To reduce age-related inequalities in the affordability of COVID-19 test, these findings support calls for exempting everyone from paying OOP for testing and, removing other type of barriers than financial ones.
Sleep patterns correlates with the efficacy of tDCS on post-stroke patients with prolonged disorders of consciousness
Authors: Yu Jie , Wu Yuehao , Wu Biwen , Xu Chuan , Cai Jiaye , Wen Xinrui , Meng Fanxia , Zhang Li , He Fangping , Hong Lirong , Gao Jian , Li Jingqi , Yu Jintai , Luo Benyan 
Published: December 2022

Abstract
Background
The subclassification of prolonged disorders of consciousness (DoC) based on sleep patterns is important for the evaluation and treatment of the disease. This study evaluates the correlation between polysomnographic patterns and the efficacy of transcranial direct current stimulation (tDCS) in patients with prolonged DoC due to stroke.

Methods
In total, 33 patients in the vegetative state (VS) with sleep cycles or without sleep cycles were randomly assigned to either active or sham tDCS groups. Polysomnography was used to monitor sleep changes before and after intervention. Additionally, clinical scale scores and electroencephalogram (EEG) analysis were performed before and after intervention to evaluate the efficacy of tDCS on the patients subclassified according to their sleep patterns.

Results
The results suggest that tDCS improved the sleep structure, significantly prolonged total sleep time (TST) (95%CI: 14.387–283.527, P = 0.013) and NREM sleep stage 2 (95%CI: 3.157–246.165, P = 0.040) of the VS patients with sleep cycles. It also significantly enhanced brain function of patients with sleep cycles, which were reflected by the increased clinical scores (95%CI: 0.340–3.440, P < 0.001), the EEG powers and functional connectivity in the brain and the 6-month prognosis. Moreover, the changes in NREM sleep stage 2 had a significant positive correlation with each index of the β band.

Conclusion
This study reveals the importance of sleep patterns in the prognosis and treatment of prolonged DoC and provides new evidence for the efficacy of tDCS in post-stroke patients with VS patients subclassified by sleep pattern.
Trial registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT03809936. Registered 18 January 2019