bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic review of individual and ecological determinants of maternal mortality in the world based on the income level of countries
Authors: Tajvar Maryam , Hajizadeh Alireza , Zalvand Rostam
Published: December 2022

Background

This systematic review was conducted to map the literature on all the existing evidence regarding individual and ecological determinants of maternal mortality in the world and to classify them based on the income level of countries. Such a systematic review had not been conducted before.

Methods

We conducted an electronic search for primary and review articles using “Maternal Mortality” and “Determinant” as keywords or MeSH terms in their Title or Abstract, indexed in Scopus, PubMed, and Google with no time or geographical limitation and also hand searching was performed for most relevant journals. STROBE and Glasgow university critical appraisal checklists were used for quality assessment of the included studies. Data of the determinants were extracted and classified into individual or ecological categories based on income level of the countries according to World Bank classification.

Results

In this review, 109 original studies and 12 review articles from 33 countries or at global level met the inclusion criteria. Most studies were published after 2013. Most literature studied determinants of low and lower-middle-income countries. The most important individual determinants in low and lower-middle-income countries were location of birth, maternal education, any delays in health services seeking, prenatal care and skilled birth attendance. Household-related determinants in low-income countries included improved water source and sanitation system, region of residence, house condition, wealth of household, and husband education. Additionally, ecological determinants including human resources, access to medical equipment and facilities, total fertility rate, health financing system, country income, poverty rate, governance, education, employment, social protection, gender inequality, and human development index were found to be important contributors in maternal mortality. A few factors were more important in higher-income countries than lower-income countries including parity, IVF births, older mothers, and type of delivery.

Conclusion

A comprehensive list of factors associated with maternal death was gathered through this systematic review, most of which were related to lower-income countries. It seems that the income level of the countries makes a significant difference in determinants of maternal mortality in the world.
Determinants of early marriage among married women in nine high fertility sub-Saharan African countries: a multilevel analysis of recent demographic and health surveys
Authors: Belachew Tadele Biresaw , Negash Wubshet Debebe , Kefale Getachew Teshale , Tafere Tesfahun Zemene , Asmamaw Desale Bihonegn
Published: December 2022

Background

Early marriage is global issue that seriously harms women’s personal development and rights. Regarding this, information about married women’s early marriage is inadequate in the world, including sub-Saharan Africa; therefore, this study aimed to assess the early marriage of women in the top nine highly fertile SSA countries.

Methods

Data for this study was obtained from the most recent Demographic and Health Surveys. A total weighted sample of 121,077 married reproductive-age women was included. A multilevel mixed-effect binary logistic regression model was fitted to identify the significant associated factors of early marriage. As a final step, the Adjusted Odds Ratio (AOR) was used with a confidence interval of 95% in determining statistical significance.

Results

Overall prevalence of early marriage was 55.11% (95% CI: 54.8, 55.4) and ranged from 28.11% in Burundi to 80.77% in Niger. The factors significantly associated with early marriage were women’s educational status; primary education (AOR = 0.39; 95% CI: 0.38, 0.41), secondary and higher (AOR = 0.1; 95% CI: 0.09, 0.11), employed (AOR = 0.73; 95% CI: 0.71, 0 .75), classified as rich wealth index level (AOR = 0.87; 95% CI: 0.85, 0.91), a number of family size ≥ 7 (AOR = 1.28; 95% CI: 1.23, 1.33), community-level poverty, (AOR = 1.28; 95% CI: 1.23, 1.33) and rural residency (AOR = 1.16;95% CI: 1.12, 1.21).

Conclusion

Marriage before the age of 18 is moderately high in high-fertility countries. Therefore, the respective countries government should give due attention to access to education, and encourage the participation of women in making marriage-related decisions, especially those residing in rural areas.
Effect of liver dysfunction on outcome of radioactive iodine therapy for Graves’ disease
Authors: Ze Yuyang , Shao Fei , Feng Xuefeng , Shen Shanmei , Bi Yan , Zhu Dalong , Zhang Xiaowen
Published: December 2022

Liver dysfunction is a common complication of Graves’ disease (GD) that may be caused by excessive thyroid hormone (TH) or anti-thyroid drugs (ATDs). Radioactive iodine (RAI) therapy is one of the first-line treatments for GD, but it is unclear whether it is safe and effective in patients with liver dysfunction. 510 consecutive patients with GD receiving first RAI were enrolled in the study, and followed up at 3-, 6- and 12-month. Liver dysfunction was recorded in 222 (43.5%) patients. GD patients with liver dysfunction had higher serum levels of free triiodothyronine (FT3) (median 27.6 vs. 20.6 pmol/L, p < 0.001) and free thyroxine (FT4) (median 65.4 vs. 53.5 pmol/L, p < 0.001) levels than those with normal liver function. Binary logistic regression analysis showed that duration of disease (OR = 0.951, 95% CI: 0.992–0.980, p = 0.001) and male gender (OR = 1.106, 95% CI: 1.116–2.384; p = 0.011) were significant differential factors for liver dysfunction. Serum TSH levels were higher in patients with liver dysfunction at all 3 follow-up time points (p = 0.014, 0.008, and 0.025 respectively). FT3 level was lower in patients with liver dysfunction at 3-month follow-up (p = 0.047), but the difference disappeared at 6 and 12 months (p = 0.351 and 0.264 respectively). The rate of euthyroidism or hypothyroidism was higher in patients with liver dysfunction than in those with normal liver function at 3 months (74.5% vs 62.5%; p = 0.005) and 6 months (82.1% vs 69.1%; p = 0.002) after RAI treatment, but the difference did not persist at 12-month follow-up (89.6% vs 83.2%, p = 0.081).There were no statistically significant differences in treatment efficacy (94.48% vs 90.31%, p = 0.142), incidence of early-onset hypothyroidism (87.73% vs 83.67%, p = 0.277), and recurrence rate (4.91% vs 7.14%, p = 0.379) between the 2 groups at 12-month follow-up. In conclusion, the efficacy of RAI was comparable in GD patients with liver dysfunction and those with normal liver function.
Increased dental visits in patients with rheumatoid arthritis: a secondary cohort analysis of population based claims data
Authors: Juan Ching-Ya , Hsu Chia-Wen , Lu Ming-Chi
Published: December 2022

Objective

To study the utilization of dental care in patients with rheumatoid arthritis (RA) and compare the incidence of common dental disorders in patients with and without RA.

Methods

This data used in this study was from the population-based Taiwan's National Health Insurance Research Database. We identified 1337 patients with newly diagnosed RA between January 2000 and December 2012. We also identified 13,370 individual without a diagnosis of RA using frequency matching on 5-year age intervals, sex, and index year. Patients with a diagnosis of primary Sjögren's syndrome were excluded. Dental disorders were identified using respective ICD-9-CM codes confirmed by dentists. The incidence and incidence rate ratio [IRR] of each dental disorders were calculated using Poisson regression.

Results

Compared with the comparison cohort, the prevalence of dentist visits in the RA cohort were significantly higher (70.3% vs. 66.7%, p = 0.008) and the frequency of dentist visits in the RA cohort were also significantly higher (median 2.67 vs. 1.78 per year, p < 0.001). In addition, the incidence of visits for dental caries (adjusted IRR 1.16, p < 0.001), pulpitis (adjusted IRR 1.12, p = 0.044), gingivitis (adjusted IRR 1.13, p = 0.027), periodontitis (adjusted IRR 1.13, p = 0.004), and oral ulcer (adjusted IRR 1.24, p = 0.003) were higher in patients with RA.

Conclusions

An elevated prevalence and frequency of dental visits were associated with patients with RA. In addition, elevated incidence of dental disorders, including dental caries, pulpitis, gingivitis, periodontitis, and oral ulceration, were observed. Oral health should be accessed regularly in patients with RA.
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

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

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

Objectives

Patients 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.

Methods

Illness 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.

Conclusion

Results 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

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

Background

Women 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.

Methods

To 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.

Results

Women 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.

Conclusions

Our 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

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

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.
Unaffordability of COVID-19 tests: assessing age-related inequalities in 83 countries
Authors: Flores Gabriela , Abbasi Asiyeh , Korachais Catherine , Lavado Rouselle
Published: December 2022

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

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
Antennal sensory structures of Phenacoccus solenopsis (Hemiptera: Pseudococcidae)
Authors: Abd El-Ghany Nesreen M. , Zhou Jing-Jiang , Dewer Youssef
Published: December 2022

Background

The cotton mealybug Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae) is one of the most devastating sap-sucking pests of cultivated plants. The success of P. solenopsis is attributable to its ecological resilience and insecticide resistance, making its control extremely difficult and expensive. Thus, alternative safe approaches are needed to prevent the pest population from reaching the economic threshold. One of these novel approaches is based on the fact that chemical communication via the olfactory system drives critical behaviors required for the survival and development of the species. This knowledge can be useful for controlling insect pests using traps based on semiochemicals. The antennae of insects are an invaluable model for studying the fundamentals of odor perception. Several efforts have been made to investigate the histological and ultrastructural organization of the olfactory organs, such as the antennae and maxillary palps, in many insect species. However, studies on the antennal sensory structures of Phenacoccus species are lacking. Furthermore, although enormous progress has been made in understanding the antennal structures of many mealybug species, the olfactory sensilla in the antennae of P. solenopsis have not yet been described. In this study, we describe, for the first time, the morphology and distribution of the antennal sensilla in male and female P. solenopsis using scanning electron microscopy.

Results

Our results revealed that the entire antennae length and the number of flagellar segments were different between the sexes. Eight morphological types of sensilla were identified on male antennae: trichoid sensilla, chaetic sensilla (three subtypes), basiconic sensilla (two subtypes), and campaniform sensilla (two subtypes). Six morphological types of sensilla were found on female antennae. Sensilla chaetica of subtype 2 and campaniform sensilla of subtype 1 were distributed only on male antennae, suggesting that these sensilla are involved in the recognition of female sex pheromones. The subtype 1 of sensilla chaetica was significantly more abundant on female antennae than on male ones, while subtype 3 was only located on the terminal flagellar segment of the antenna in both sexes.

Conclusions

This study provides insightful information for future electrophysiological and behavioral studies on chemical communication in insects, particularly the cotton mealybug, P. solenopsis that could help in developing new strategies for controlling this economically important insect species.
Design and validation of a multi-task, multi-context protocol for real-world gait simulation
Authors: Scott Kirsty , Bonci Tecla , Salis Francesca , Alcock Lisa , Buckley Ellen , Gazit Eran , Hansen Clint , Schwickert Lars , Aminian Kamiar , Bertuletti Stefano , Caruso Marco , Chiari Lorenzo , Sharrack Basil , Maetzler Walter , Becker Clemens , Hausdorff Jeffrey M. , Vogiatzis Ioannis , Brown Philip , Del Din Silvia , Eskofier Björn , Paraschiv-Ionescu Anisoara , Keogh Alison , Kirk Cameron , Kluge Felix , Micó-Amigo Encarna M. , Mueller Arne , Neatrour Isabel , Niessen Martijn , Palmerini Luca , Sillen Henrik , Singleton David , Ullrich Martin , Vereijken Beatrix , Froehlich Marcel , Brittain Gavin , Caulfield Brian , Koch Sarah , Carsin Anne-Elie , Garcia-Aymerich Judith , Kuederle Arne , Yarnall Alison , Rochester Lynn , Cereatti Andrea , Mazzà Claudia ,   for the Mobilise-D consortium
Published: December 2022

Background

Measuring mobility in daily life entails dealing with confounding factors arising from multiple sources, including pathological characteristics, patient specific walking strategies, environment/context, and purpose of the task. The primary aim of this study is to propose and validate a protocol for simulating real-world gait accounting for all these factors within a single set of observations, while ensuring minimisation of participant burden and safety.

Methods

The protocol included eight motor tasks at varying speed, incline/steps, surface, path shape, cognitive demand, and included postures that may abruptly alter the participants’ strategy of walking. It was deployed in a convenience sample of 108 participants recruited from six cohorts that included older healthy adults (HA) and participants with potentially altered mobility due to Parkinson’s disease (PD), multiple sclerosis (MS), proximal femoral fracture (PFF), chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF). A novelty introduced in the protocol was the tiered approach to increase difficulty both within the same task (e.g., by allowing use of aids or armrests) and across tasks.

Results

The protocol proved to be safe and feasible (all participants could complete it and no adverse events were recorded) and the addition of the more complex tasks allowed a much greater spread in walking speeds to be achieved compared to standard straight walking trials. Furthermore, it allowed a representation of a variety of daily life relevant mobility aspects and can therefore be used for the validation of monitoring devices used in real life.

Conclusions

The protocol allowed for measuring gait in a variety of pathological conditions suggests that it can also be used to detect changes in gait due to, for example, the onset or progression of a disease, or due to therapy.

Trial registration: ISRCTN—12246987.
Estimation of the mortality rate of workers in Japan
Authors: Kimura Tatsuki , Sasaki Michiya , Hattori Takatoshi
Published: December 2022

Background

Risk-based decision-making is used to identify risk factors for which threshold points have not been identified. The occupational mortality rate was referred to as a reference risk. This study aimed to analyze recent trends in worker mortality using three data sources.

Methods

The Reports of Worker Casualties (RWC), the Annual Statistics Report of the Industrial Accident Compensation Insurance Council (ASR), and the Annual Business Report of the Industrial Accident Compensation Insurance Council (ABR) were used. Mortality rates were estimated by age group and industry category (overall, and manufacturing and construction industries) from 1991 to 2019. The mortality rates were compared with those estimated in Western countries.

Results

The mortality rates for the three industry categories in the RWC and ASR decreased, whereas those for the manufacturing and construction industries in the ABR did not. In 2019, the mortality rates in the ABR were 3.1, 4.8, and 3.1 times higher than those in the RWC overall and in the manufacturing and construction industries, respectively. The differences decreased when deaths after long-term medical treatment were considered. The mortality rate trends in Japan were similar to those in Western countries. The upper mortality rate among Japan and Western countries was at least five to 15 times higher than the lowest.

Conclusion

When occupational mortality rates are used as a reference risk, it is important to consider any changes with time, the data sources used, and the differences between countries.
Lower Extremity Staged Revascularization (LESR) as a new innovative concept for lower extremity salvage in acute popliteal artery injuries: a hypothesis
Authors: Edwards Joseph , Treffalls Rebecca N. , Abdou Hossam , Stonko David P. , Walker Patrick F. , Morrison Jonathan J.
Published: December 2022

Popliteal artery injury following knee dislocation is associated with significant morbidity and high amputation rates. The complex and multi-disciplinary input required to manage this injury effectively can take time to arrange, prolonging the time to revascularization. Furthermore, open surgical bypass or interposition graft can be technically challenging in the acute setting, further prolonging ischemic time.

Temporary intravascular shunts can be used to temporarily restore flow but require surgical exposure which takes time. Endovascular techniques can decrease the time to revascularization; however, endovascular popliteal stent-grafting is controversial because the biomechanical forces relating to flexion and extension of the knee may increase the risk of stent thrombosis. An ideal operation would result in rapid revascularization, eventually leading to a definitive and durable surgical solution.

We hypothesize that a staged approach combing extracorporeal shunting, temporary endovascular covered stent placement, external fixation of bony injury, and definitive open repair provides for a superior approach to popliteal artery injury than current standard of care. We term this approach lower extremity staged revascularization (LESR) and the aim is to minimize the known factors contributing to poor outcomes after traumatic popliteal artery injury.
Acetyltransferase NAT10 regulates the Wnt/β-catenin signaling pathway to promote colorectal cancer progression via ac4C acetylation of KIF23 mRNA
Authors: Jin Chi , Wang Tuo , Zhang Dongsheng , Yang Peng , Zhang Chuan , Peng Wen , Jin Kangpeng , Wang Lu , Zhou Jiahui , Peng Chaofan , Tan Yuqian , Ji Jiangzhou , Chen Zhihao , Sun Qingyang , Yang Sheng , Tang Junwei , Feng Yifei , Sun Yueming
Published: December 2022

Background

N4-acetylcytidine (ac4C) as a significant RNA modification has been reported to maintain the stability of mRNA and to regulate the translation process. However, the roles of both ac4C and its ‘writer’ protein N-acetyltransferase 10 (NAT10) played in the disease especially colorectal cancer (CRC) are unclear. At this point, we discover the underlying mechanism of NAT10 modulating the progression of CRC via mRNA ac4C modification.

Methods

The clinical significance of NAT10 was explored based on the TCGA and GEO data sets and the 80 CRC patients cohort of our hospital. qRT-PCR, dot blot, WB, and IHC were performed to detect the level of NAT10 and ac4C modification in CRC tissues and matched adjacent tissues. CCK-8, colony formation, transwell assay, mouse xenograft, and other in vivo and in vitro experiments were conducted to probe the biological functions of NAT10. The potential mechanisms of NAT10 in CRC were clarified by RNA-seq, RIP-seq, acRIP-seq, luciferase reporter assays, etc.

Results

The levels of NAT10 and ac4C modification were significantly upregulated. Also, the high expression of NAT10 had important clinical values like poor prognosis, lymph node metastasis, distant metastasis, etc. Furthermore, the in vitro experiments showed that NAT10 could inhibit apoptosis and enhance the proliferation, migration, and invasion of CRC cells and also arrest them in the G2/M phase. The in vivo experiments discovered that NAT10 could promote tumor growth and liver/lung metastasis. In terms of mechanism, NAT10 could mediate the stability of KIF23 mRNA by binding to its mRNA 3’UTR region and up-regulating its mRNA ac4c modification. And then the protein level of KIF23 was elevated to activate the Wnt/β-catenin pathway and more β-catenin was transported into the nucleus which led to the CRC progression. Besides, the inhibitor of NAT10, remodelin, was applied in vitro and vivo which showed an inhibitory effect on the CRC cells.

Conclusions

NAT10 promotes the CRC progression through the NAT10/KIF23/GSK-3β/β-catenin axis and its expression is mediated by GSK-3β which forms a feedback loop. Our findings provide a potential prognosis or therapeutic target for CRC and remodelin deserves more attention.

Graphical Abstract
Automated assembly scaffolding using RagTag elevates a new tomato system for high-throughput genome editing
Authors: Alonge Michael , Lebeigle Ludivine , Kirsche Melanie , Jenike Katie , Ou Shujun , Aganezov Sergey , Wang Xingang , Lippman Zachary B. , Schatz Michael C. , Soyk Sebastian
Published: December 2022

Advancing crop genomics requires efficient genetic systems enabled by high-quality personalized genome assemblies. Here, we introduce RagTag, a toolset for automating assembly scaffolding and patching, and we establish chromosome-scale reference genomes for the widely used tomato genotype M82 along with Sweet-100, a new rapid-cycling genotype that we developed to accelerate functional genomics and genome editing in tomato. This work outlines strategies to rapidly expand genetic systems and genomic resources in other plant species.
Intravenous acetaminophen with morphine versus intravenous morphine alone for acute pain in the emergency room: protocol for a multicenter, randomized, placebo-controlled, double-blinded study (ADAMOPA)
Authors: Cattin Guillaume , Jenvrin Joel , Hardouin Jean Benoit , Longo Céline , Montassier Emmanuel
Published: December 2022

Background

In emergency medicine, pain is a frequent reason for consultation. However, there is a great variation in its management which is often insufficient. The use intravenous morphine alone or multimodal analgesia with paracetamol is recommended for severe pain. But robust data are lacking to justify the association of paracetamol with morphine versus morphine alone for pain management in the emergency room (ER). The aim of our study is therefore to assess if in patients with acute pain of moderate to severe intensity with a numerical verbal scale (NVS) ≥5 in the ER, the intravenous administration of morphine alone is not inferior to the administration of intravenous morphine combined with paracetamol at 30 min from the first administration of the study drug.

Methods

ADAMOPA is a prospective, non-inferiority, multicenter, placebo-controlled, parallel-group, randomized (1:1), double-blind trial. Subjects will be enrolled in the ER if they experience moderate to severe, acute, non-traumatic, and traumatic pain, defined as an NVS ≥5. The primary endpoint will be the between-group difference in mean change in NVS pain scores among patients receiving the combination of intravenous morphine plus paracetamol or intravenous morphine given alone, measured from the time before administration of the study medication to 30 min later.

Discussion

This trial will determine the clinical utility of the association of paracetamol with morphine for pain management in the emergency room. The ADAMOPA trial will be conducted in accordance with the International Council on Harmonization Good Clinical Practices.

Trial registration

EudraCT number: 2019-002149-39. ClinicalTrials.gov identifier: NCT04148495. Date of trial registration: November 1, 2019.
Cryptosporidium parvum regulates HCT-8 cell autophagy to facilitate survival via inhibiting miR-26a and promoting miR-30a expression
Authors: Jiang Heng , Zhang Xu , Li Xin , Wang Xiaocen , Zhang Nan , Gong Pengtao , Zhang Xichen , Yu Yanhui , Li Jianhua
Published: December 2022

Background

Cryptosporidium parvum is an important zoonotic parasite, which not only causes economic losses in animal husbandry but also harms human health. Due to the lack of effective measures for prevention and treatment, it is important to understand the pathogenesis and survival mechanism of C. parvum. Autophagy is an important mechanism of host cells against parasite infection through key regulatory factors such as microRNAs and MAPK pathways. However, the regulatory effect of C. parvum on autophagy has not been reported. Here, we demonstrated that C. parvum manipulated autophagy through host cellular miR-26a, miR-30a, ERK signaling and P38 signaling for parasite survival.

Methods

The expression of Beclin1, p62, LC3, ERK and P38 was detected using western blotting in HCT-8 cells infected with C. parvum as well as treated with miR-26a-mimic, miR-30a-mimic, miR-26a-mimic or miR-30a-inhibitor post C. parvum infection. The qPCR was used to detect the expression of miR-26a and miR-30a and the number of C. parvum in HCT-8 cells. Besides, the accumulation of autophagosomes was examined using immunofluorescence.

Results

The expression of Beclin1 and p62 was increased, whereas LC3 expression was increased initially at 0–8 h but decreased at 12 h and then increased again in C. parvum-infected cells. C. parvum inhibited miR-26a-mimic-induced miR-26a but promoted miR-30a-mimic-induced miR-30a expression. Suppressing miR-30a resulted in increased expression of LC3 and Beclin1. However, upregulation of miR-26a reduced ERK/P38 phosphorylation, and inhibiting ERK/P38 signaling promoted Beclin1 and LC3 while reducing p62 expression. Treatment with miR-26a-mimic, autophagy inducer or ERK/P38 signaling inhibitors reduced but treatment with autophagy inhibitor or miR-30a-mimic increased parasite number.

Conclusions

The study found that C. parvum could regulate autophagy by inhibiting miR-26a and promoting miR-30a expression to facilitate the proliferation of parasites. These results revealed a new mechanism for the interaction of C. parvum with host cells.

Graphical Abstract
The role of miRNA and lncRNA in heterotopic ossification pathogenesis
Authors: Pulik Łukasz , Mierzejewski Bartosz , Sibilska Aleksandra , Grabowska Iwona , Ciemerych Maria Anna , Łęgosz Paweł , Brzóska Edyta
Published: December 2022

Heterotopic ossification (HO) is the formation of bone in non-osseous tissues, such as skeletal muscles. The HO could have a genetic or a non-genetic (acquired) background, that is, it could be caused by musculoskeletal trauma, such as burns, fractures, joint arthroplasty (traumatic HO), or cerebral or spinal insult (neurogenetic HO). HO formation is caused by the differentiation of stem or progenitor cells induced by local or systemic imbalances. The main factors described so far in HO induction are TGFβ1, BMPs, activin A, oncostatin M, substance P, neurotrophin-3, and WNT. In addition, dysregulation of noncoding RNAs, such as microRNA or long noncoding RNA, homeostasis may play an important role in the development of HO. For example, decreased expression of miRNA-630, which is responsible for the endothelial–mesenchymal transition, was observed in HO patients. The reduced level of miRNA-421 in patients with humeral fracture was shown to be associated with overexpression of BMP2 and a higher rate of HO occurrence. Down-regulation of miRNA-203 increased the expression of runt-related transcription factor 2 (RUNX2), a crucial regulator of osteoblast differentiation. Thus, understanding the various functions of noncoding RNAs can reveal potential targets for the prevention or treatment of HO.
Distinct mechanisms mediating therapy-induced cellular senescence in prostate cancer
Authors: Kallenbach Julia , Atri Roozbahani Golnaz , Heidari Horestani Mehdi , Baniahmad Aria
Published: December 2022

Background

Prostate cancer (PCa) is an age-related malignancy in men with a high incidence rate. PCa treatments face many obstacles due to cancer cell resistance and many bypassing mechanisms to escape therapy. According to the intricacy of PCa, many standard therapies are being used depending on PCa stages including radical prostatectomy, radiation therapy, androgen receptor (AR) targeted therapy (androgen deprivation therapy, supraphysiological androgen, and AR antagonists) and chemotherapy. Most of the aforementioned therapies have been implicated to induce cellular senescence. Cellular senescence is defined as a stable cell cycle arrest in the G1 phase and is one of the mechanisms that prevent cancer proliferation.

Results

In this review, we provide and analyze different mechanisms of therapy-induced senescence (TIS) in PCa and their effects on the tumor. Interestingly, it seems that different molecular pathways are used by cancer cells for TIS. Understanding the complexity and underlying mechanisms of cellular senescence is very critical due to its role in tumorigenesis. The most prevalent analyzed pathways in PCa as TIS are the p53/p21WAF1/CIP1, the p15INK4B/p16INK4A/pRb/E2F/Cyclin D, the ROS/ERK, p27Kip1/CDK/pRb, and the p27Kip1/Skp2/C/EBP β signaling. Despite growth inhibition, senescent cells are highly metabolically active. In addition, their secretome, which is termed senescence-associated secretory phenotype (SASP), affects within the tumor microenvironment neighboring non-tumor and tumor cells and thereby may regulate the growth of tumors. Induction of cancer cell senescence is therefore a double-edged sword that can lead to reduced or enhanced tumor growth.

Conclusion

Thus, dependent on the type of senescence inducer and the specific senescence-induced cellular pathway, it is useful to develop pathway-specific senolytic compounds to specifically targeting senescent cells in order to evict senescent cells and thereby to reduce SASP side effects.