bluuebunny/crossref_metadata_2025 huggingface dataset:
Protocol for long-term effect of pulmonary rehabilitation under nintedanib in idiopathic pulmonary fibrosis
Authors: Nishiyama Osamu , Kataoka Kensuke , Ando Masahiko , Arizono Shinichi , Morino Akira , Nishimura Koichi , Ogawa Tomoya , Shiraki Akira , Watanabe Fumiko , Kozu Ryo , Ogura Takashi , Kondoh Yasuhiro
Published: June 2021

Background

Pulmonary rehabilitation causes short-term improvement in exercise capacity, dyspnoea and health-related quality of life in idiopathic pulmonary fibrosis (IPF); however, long-term maintenance of the improvement is difficult. Nintedanib, an antifibrotic drug, has been shown to delay the worsening of pulmonary function in IPF. Therefore, the concomitant use of nintedanib with pulmonary rehabilitation is anticipated to contribute to the long-term maintenance of the pulmonary rehabilitation effects. The long-term effect of pulmonary rehabilitation under nintedanib treatment in IPF (FITNESS) study is a multicenter, randomised, prospective, parallel-group, open-label trial.

Methods

The study will enrol 84 patients with IPF who have been treated with nintedanib. Patients in the pulmonary rehabilitation group will receive a programmed short-term induction pulmonary rehabilitation programme, followed by a maintenance home-based pulmonary rehabilitation programme, while patients in the control group will receive usual outpatient care. Patients in both groups will continue to receive nintedanib treatment throughout the study period. The primary end-point of the study is to compare the change in the 6-min walk distance from the baseline to 12 months between the pulmonary rehabilitation and control groups. The main secondary end-point is endurance exercise time, measured using a bicycle ergometer.

Discussion

FITNESS is the first randomised controlled study to evaluate the long-term effects of pulmonary rehabilitation in IPF treated with nintedanib. This study will address the hypothesis that concomitant use of nintedanib contributes to the maintenance of long-term effects of pulmonary rehabilitation, thus leading to a comprehensive therapeutic approach of “nintedanib and pulmonary rehabilitation” in the antifibrotic era.
Clinical relevance of depressed kynurenine pathway in episodic migraine patients: potential prognostic markers in the peripheral plasma during the interictal period
Authors: Tuka Bernadett , Nyári Aliz , Cseh Edina Katalin , Körtési Tamás , Veréb Dániel , Tömösi Ferenc , Kecskeméti Gábor , Janáky Tamás , Tajti János , Vécsei László
Published: June 2021

Background

Altered glutamatergic neurotransmission and neuropeptide levels play a central role in migraine pathomechanism. Previously, we confirmed that kynurenic acid, an endogenous glutamatergic antagonist, was able to decrease the expression of pituitary adenylate cyclase-activating polypeptide 1–38, a neuropeptide with known migraine-inducing properties. Hence, our aim was to reveal the role of the peripheral kynurenine pathway (KP) in episodic migraineurs. We focused on the complete tryptophan (Trp) catabolism, which comprises the serotonin and melatonin routes in addition to kynurenine metabolites. We investigated the relationship between metabolic alterations and clinical characteristics of migraine patients.

Methods

Female migraine patients aged between 25 and 50 years (n = 50) and healthy control subjects (n = 34) participated in this study. Blood samples were collected from the cubital veins of subjects (during both the interictal/ictal periods in migraineurs,n = 47/12, respectively). 12 metabolites of Trp pathway were determined by neurochemical measurements (UHPLC-MS/MS).

Results

Plasma concentrations of the most Trp metabolites were remarkably decreased in the interictal period of migraineurs compared to healthy control subjects, especially in the migraine without aura (MWoA) subgroup: Trp (p < 0.025), L-kynurenine (p < 0.001), kynurenic acid (p < 0.016), anthranilic acid (p < 0.007), picolinic acid (p < 0.03), 5-hydroxy-indoleaceticacid (p < 0.025) and melatonin (p < 0.023). Several metabolites showed a tendency to elevate during the ictal phase, but this was significant only in the cases of anthranilic acid, 5-hydroxy-indoleaceticacid and melatonin in MWoA patients. In the same subgroup, higher interictal kynurenic acid levels were identified in patients whose headache was severe and not related to their menstruation cycle. Negative linear correlation was detected between the interictal levels of xanthurenic acid/melatonin and attack frequency. Positive associations were found between the ictal 3-hydroxykynurenine levels and the beginning of attacks, just as between ictal picolinic acid levels and last attack before ictal sampling.

Conclusions

Our results suggest that there is a widespread metabolic imbalance in migraineurs, which manifests in a completely depressed peripheral Trp catabolism during the interictal period. It might act as trigger for the migraine attack, contributing to glutamate excess induced neurotoxicity and generalised hyperexcitability. This data can draw attention to the clinical relevance of KP in migraine.
A two-way rectification method for identifying differentially expressed genes by maximizing the co-function relationship
Authors: Chen Bolin , Gao Li , Shang Xuequn
Published: June 2021

Background

The identification of differentially expressed genes (DEGs) is an important task in many biological studies. The currently widely used methods often calculate a score for each gene by estimating the significance level in terms of the differential expression. However, biological experiments often have only three duplications, plus plenty of noises contain in gene expression datasets, which brings a great challenge to statistical analysis methods. Moreover, the abundance of gene expression levels are not evenly distributed. Thus, those low expressed genes are more easily to be detected by fold-change based methods, which may results in high false positives among the DEG list. Since phenotypical changes result from DEGs should be strongly related to several distinct cellular functions, a more robust method should be designed to increase the true positive rate of the functional related DEGs.

Results

In this study, we propose a two-way rectification method for identifying DEGs by maximizing the co-function relationships between genes and their enriched cellular pathways. An iteration strategy is employed to sequentially narrow down the group of identified DEGs and their associated biological functions. Functional analyses reveal that the identified DEGs are well organized in the form of functional modules, and the enriched pathways are very significant with lower p-value and larger gene count.

Conclusions

An integrative rectification method was proposed to identify key DEGs and their related functions simultaneously. The experimental validations demonstrate that the method has high interpretability and feasibility. It performs very well in terms of the identification of remarkable functional related genes.
The impact of tube replacement timing during LCIG therapy on PEG-J associated adverse events: a retrospective multicenter observational study
Authors: Yamashita Kanefumi , Yube Yukinori , Yamazaki Yukinao , Fukuchi Takehide , Kato Masaki , Koike Tomoyuki , Uehara Takeshi , Ikeda Yoshiou , Furune Satoshi , Murakami Hidehiro , Kubota Eiji , Fujioka Shinsuke , Sato Yoshinori , Jin Xiaoyi , Suzuki Tomohiko , Furukawa Kazuhiro , Tsuboi Yoshio
Published: June 2021

Background

Levodopa–carbidopa intestinal gel (LCIG) treatment, a unique drug delivery system for patients with advanced Parkinson’s disease (PD), is covered by health insurance in Japan since September 2016. Various LCIG procedure/device-associated adverse events (AEs) have been reported; however, reports on their treatment have been limited. This is the first multicenter study to clarify the frequency and timing of device-related AEs.

Methods

Between September 2016 and December 2018, 104 patients introduced to the LCIG treatment for advanced PD in 11 hospitals were included. The patients’ characteristics, AEs incidence, AEs time, and tube exchange time were investigated.

Results

The median follow-up period was 21.5 months. Minor AE cases were 29.4%, whereas major AE cases were 43.1%. Majority of major AEs (n = 55, 94.8%) were managed with endoscopic treatment, such as tube exchange. Few severe AEs required surgical treatment (n =3, 5.2%). The mean (range) exposure to percutaneous endoscopic gastrojejunostomy (PEG-J) was 14.7 (0–33) months. One year after the LCIG treatment introduction, 55 patients (54.0%) retained the original PEG-J tube. The mean PEG-J tube exchange time was 10.8 ± 7.0 months in all patients, 11.6 ± 4.7 and 10.5 ± 7.7 months in patients with scheduled exchange and who underwent exchange due to AEs, respectively.

Conclusions

Some device-related AEs occurred during the LCIG treatment; however, only few were serious, most of which could be treated with simple procedures or tube replacement with endoscopy. Therefore, the LCIG treatment is feasible and safe and is a unique treatment option for PD, requiring endoscopists’ understanding and cooperation.
Nomogram for perinatal prediction of intrapartum fever: a retrospective case–control study
Authors: Jiang Zhenfei , Hu Xiaoyi , Zeng Huabei , Wang Xinghe , Tan Cheng , Ni Chunyan , Dai Lingyun , Liu Su
Published: June 2021

Objective

To explore the risk factors for intrapartum fever and to develop a nomogram to predict the incidence of intrapartum fever.

Methods

The general demographic characteristics and perinatal factors of 696 parturients who underwent vaginal birth at the Affiliated Hospital of Xuzhou Medical University from May 2019 to April 2020 were retrospectively analysed. Data was collected from May 2019 to October 2019 on 487 pregnant women who formed a training cohort. A multivariate logistic regression model was used to identify the independent risk factors associated with intrapartum fever during vaginal birth, and a nomogram was developed to predict the occurrence. To verify the nomogram, data was collected from January 2020 to April in 2020 from 209 pregnant women who formed a validation cohort.

Results

The incidence of intrapartum fever in the training cohort was found in 72 of the 487 parturients (14.8%), and the incidence of intrapartum fever in the validation cohort was 31 of the 209 parturients (14.8%). Multivariate logistic regression analysis showed that the following factors were significantly related to intrapartum fever: primiparas (odds ratio [OR] 2.43; 95% confidence interval [CI] 1.15–5.15), epidural labour analgesia (OR 2.89; 95% CI 1.23–6.82), premature rupture of membranes (OR 2.37; 95% CI 1.13–4.95), second stage of labour ≥ 120 min (OR 4.36; 95% CI 1.42–13.41), amniotic fluid pollution degree III (OR 10.39; 95% CI 3.30–32.73), and foetal weight ≥ 4000 g (OR 7.49; 95% CI 2.12–26.54). Based on clinical experience and previous studies, the duration of epidural labour analgesia also appeared to be a meaningful factor for intrapartum fever; therefore, these seven variables were used to develop a nomogram to predict intrapartum fever in parturients. The nomogram achieved a good area under the ROC curve of 0.86 and 0.81 in the training and in the validation cohorts, respectively. Additionally, the nomogram had a well-fitted calibration curve, which also showed excellent diagnostic performance.

Conclusion

We constructed a model to predict the occurrence of fever during childbirth and developed an accessible nomogram to help doctors assess the risk of fever during childbirth. Such assessment may be helpful in implementing reasonable treatment measures.

Trial registration

Clinical Trial Registration: (www.chictr.org.cnChiCTR2000035593)
Fecundability in reproductive aged women at risk of sexual dysfunction and associated risk factors: a prospective preconception cohort study
Authors: Loy See Ling , Ku Chee Wai , Cheung Yin Bun , Godfrey Keith M. , Chong Yap-Seng , Shek Lynette Pei-Chi , Tan Kok Hian , Yap Fabian Kok Peng , Bernard Jonathan Y. , Chen Helen , Chan Shiao-Yng , Tan Tse Yeun , Chan Jerry Kok Yen
Published: June 2021

Background

Female sexual dysfunction (FSD) is a prevalent problem, affecting up to 41% of reproductive aged women worldwide. However, the association between female sexual function (FSF) and fecundability in women attempting to conceive remains unclear. We aimed 1) to examine the association between FSF in reproductive-aged preconception Asian women and fecundability, as measured by time-to-pregnancy in menstrual cycles, and 2) to examine lifestyle and behavioral factors associated with FSF.

Methods

From the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) prospective cohort, we evaluated FSF using the 6-item Female Sexual Function Index (FSFI-6) and ascertained time-to-pregnancy within a year of baseline assessment. We estimated fecundability ratio (FR) and 95% confidence interval (CI) using the discrete-time proportional hazards model, accounting for left-truncation and right censoring. We used multivariable logistic and linear regression models to identify potential factors related to FSF.

Results

Among 513 participants, 58.9% had low FSF as defined by a total FSFI-6 score at or below the median value of 22. Compared to women with high FSF, those with low FSF had a 27% reduction in fecundability (FR 0.73; 95% CI 0.54, 0.99), with adjustment for age, ethnicity, education, parity and body mass index. Overall, the FRs generally reduced with decreasing FSFI-6 scores. Physical activity, obesity, absence of probable depression and anxiety were independently associated with reduced odds of low FSF and increased FSFI-6 scores, after adjusting for sociodemographic characteristics.

Conclusions

Low FSF is associated with a longer time-to-pregnancy. Early evaluation and optimization of FSF through increased physical activity and optimal mental health may help to improve female fecundity. The finding of obese women having improved FSF remains uncertain which warrants further investigations on plausibly mechanisms. In general, the current finding highlights the importance of addressing FSF in preconception care service for general women, which is currently lacking as part of the fertility promotion effort in the country.
Design preferences for global scale: a mixed-methods study of “glocalization” of an animated, video-based health communication intervention
Authors: Adam Maya , Chase Rachel P. , McMahon Shannon A. , Kuhnert Kira-Leigh , Johnston Jamie , Ward Victoria , Prober Charles , Bärnighausen Till
Published: June 2021

Background

Designing health communication interventions for global scaling promotes health literacy and facilitates rapid global health messaging. Limited literature explores preferences for animation prototypes and other content characteristics across participants in different global regions. Prior research underscores an urgent need for health communication interventions that are compelling and accessible across culturally and geographically diverse audiences. This study presents feedback from global learners on animation design preferences and other key considerations for the development of educational video content intended for global adaptation and scaling.

Methods

We used a mixed-methods, sequential explanatory design, with a qualitative descriptive approach to the analysis of the qualitative data. We recruited participants from an international group of learners enrolled in a massive open online course. Through an online quantitative survey (n = 330), we sought preferences from participants in 73 countries for animation design prototypes to be used in video-based health communication interventions. To learn more about these preferences, we conducted in-depth interviews (n = 20) with participants selected using maximum variation purposive sampling.

Results

Generally, respondents were willing to accept animation prototypes that were free of cultural and ethnic identifiers and believed these to be preferable for globally scalable health communication videos. Diverse representations of age, gender roles, and family structure were also preferred and felt to support inclusive messaging across cultures and global regions. Familiar-sounding voiceovers using local languages, dialects, and accents were preferred for enhancing local resonance. Across global regions, narratives were highlighted as a compelling approach to facilitating engagement and participants preferred short videos with no more than two or three health messages.

Conclusions

Our findings suggest that global learners may be willing to accept simplified visuals, designed for broad cross-cultural acceptability, especially if the content is localized in other ways, such as through the use of locally resonating narratives and voiceovers. Diverse, inclusive portrayals of age, gender roles and family structure were preferred.
Self-reported changes in work situation – a cross-sectional study of patients 7 years after treatment for stress-related exhaustion
Authors: Beno Anja , Hensing Gunnel , Lindegård Agneta , Jonsdottir Ingibjörg H.
Published: June 2021

Background

Exhaustion disorder (ED) is a common cause of sick leave in Sweden, and patients often have long-lasting symptoms and reduced work capacity. The aim of this study was to explore whether patients with ED had made any changes in their work situation from the period of treatment and up to 7 years later.

Methods

In this cross-sectional study, patients diagnosed with ED at a specialist outpatient clinic were followed up after 7 years (n = 217). They received questionnaires at baseline covering sex, age, marital status, level of education, and symptoms of burnout, depression, and anxiety measured with the Shirom-Melamed Burnout Questionnaire and the Hospital Anxiety and Depression Scale. After 7 years, they were sent a follow-up questionnaire asking about their work situation and work-related stressors both before they fell sick and at the 7-year follow-up. There were three questions on work situation (change of workplace, change of work tasks, and change of working hours), and 155 patients responded to all three.

Results

After 7 years, the majority of the patients (63%; n = 98/155) reported that they had made some kind of change at work. Women were more likely than men to report decreased working hours (p = 0.001), and work-related stressors such as conflicts at work, reorganization, deficient leadership, and general discontent with the work situation were significantly more common at baseline in the group who had made changes at work. Patients who made no changes at work experienced more work-related stress due to quantitative demands in the 7-year follow-up.

Conclusion

The majority of the patients with ED made some kind of change in their work situation, and gender differences were found for changes of work tasks and working hours. Work-related stressors might be decisive for making changes at work.
Lifestyle changes during the first wave of the COVID-19 pandemic: a cross-sectional survey in the Netherlands
Authors: van der Werf Esther T. , Busch Martine , Jong Miek C. , Hoenders H. J. Rogier
Published: June 2021

Background

During the Covid-19 pandemic the Dutch government implemented its so-called ‘intelligent lockdown’ in which people were urged to leave their homes as little as possible and work from home. This life changing event may have caused changes in lifestyle behaviour, an important factor in the onset and course of diseases. The overarching aim of this study is to determine life-style related changes during the first wave of the COVID-19 pandemic among a representative sample of the adult population in the Netherlands.

Methods

Life-style related changes were studied among a random representative sample of the adult population in the Netherlands using an online survey conducted from 22 to 27 May 2020. Differences in COVID-19-related lifestyle changes between Complementary and Alternative Medicine (CAM) users and non-CAM users were determined. The survey included a modified version of the I-CAM-Q and 26 questions on lifestyle related measures, anxiety, and need for support to maintain lifestyle changes.

Results

1004 respondents were included in the study, aged between 18 and 88 years (50.7% females). Changes to a healthier lifestyle were observed in 19.3% of the population, mainly due to a change in diet habits, physical activity and relaxation, of whom 56.2% reported to be motivated to maintain this behaviour change in a post-COVID-19 era. Fewer respondents (12.3%) changed into an unhealthier lifestyle. Multivariable logistic regression analyses revealed that changing into a healthier lifestyle was positively associated with the variables ‘Worried/Anxious getting COVID-19’ (OR: 1.56, 95% C.I. 1.26–1.93), ‘CAM use’ (OR: 2.04, 95% C.I. 1.38–3.02) and ‘stress in relation to financial situation’ (OR: 1.89, 95% C.I. 1.30–2.74). ‘Age’ (OR 18–25: 1.00, OR 25–40: 0.55, 95% C.I. 0.31–0.96, OR 40–55:0.50 95% C.I. 0.28–0.87 OR 55+: 0.1095% C.I. 0.10–0.33), ‘stress in relation to health’ (OR: 2.52, 95% C.I. 1.64–3.86) and ‘stress in relation to the balance work and home’ (OR: 1.69, 95% C.I. 1.11–2.57) were found predicting the change into an unhealthier direction.

Conclusion

These findings suggest that the coronavirus crisis resulted in a healthier lifestyle in one part and, to a lesser extent, in an unhealthier lifestyle in another part of the Dutch population. Further studies are warranted to see whether this behavioural change is maintained over time, and how different lifestyle factors can affect the susceptibility for and the course of COVID-19.
Bioactive fractions and compound of Ardisia crispa roots exhibit anti-arthritic properties mediated via angiogenesis inhibition in vitro
Authors: Blin Joan Anak , Hamid Roslida Abdul , Khaza’ai Huzwah
Published: June 2021

Background

Ardisia crispa (Thunb.) A.DC (Primulaceae), is a medicinal herb traditionally used by Asian people as remedies to cure inflammatory related diseases, including rheumatism. The plant roots possess various pharmacological activities including antipyretic, anti-inflammation and antitumor. Previous phytochemical studies of the plant roots have identified long chain alkyl-1,4-benzoquinones as major constituents, together with other phytochemicals. Hexane fraction of the plant roots (ACRH), was previously reported with anti-angiogenic and anti-arthritic properties, while its effect on their anti-arthritic in vitro, is yet unrevealed. Considering the significance of angiogenesis inhibition in developing new anti-arthritic agent, thus we investigated the anti-arthritic potential of Ardisia crispa roots by suppressing angiogenesis, in vitro.

Methods

Ardisia crispa roots hexane extract (ACRH) was prepared from the plant roots using absolute n-hexane. ACRH was fractionated into quinone-rich fraction (QRF) and further isolated to yield benzoquinonoid compound (BQ), respectively. In vitro experiments using VEGF-induced human umbilical vein endothelial cells (HUVECs) and IL-1β-induced human fibroblast-like synoviocytes for rheumatoid arthritis (HFLS-RA) were performed to evaluate the effects of these samples on VEGF-induced HUVECs proliferation and tube formation, and towards IL-1β-induced HFLS-RA proliferation, invasion, and apoptosis, respectively. Therapeutic concentrations (0.05, 0.5, and 5 μg/mL) tested in this study were predetermined based on the IC50 values obtained from the MTT assay.

Results

ACRH, QRF, and BQ exerted concentration-independent antiproliferative effects on VEGF-induced HUVECs and IL-1β-induced HFLS-RA, with IC50 values at 1.09 ± 0.18, 3.85 ± 0.26, and 1.34 ± 0.16 μg/mL in HUVECs; and 3.60 ± 1.38, 4.47 ± 0.34, and 1.09 ± 0.09 μg/mL in HFLS-RA, respectively. Anti-angiogenic properties of these samples were verified via significant inhibition on VEGF-induced HUVECs tube formation, in a concentration-independent manner. The invasiveness of IL-1β-induced HFLS-RA was also significantly inhibited in a concentration-independent manner by all samples. ACRH and BQ, but not QRF, significantly enhanced the apoptosis of IL-1β-induced HFLS-RA elicited at their highest concentration (5 μg/mL) (P < 0.05).

Conclusions

These findings highlight the bioactive fractions and compound from Ardisia crispa roots as potential anti-arthritic agents by inhibiting both HUVECs and HFLS-RA’s cellular functions in vitro, possibly mediated via their anti-angiogenic effects.
Characterization of the antibacterial activity from ethanolic extracts of the botanical, Larrea tridentata
Authors: Turner Tiffany , Ruiz Guillermo , Gerstel Johanne , Langland Jeffrey
Published: June 2021

Background

β-lactam antibiotics are a class of broad-spectrum antibiotics consisting of all antibiotic agents that contain a β-lactam ring in their molecular structures. β-lactam antibiotics are only known to be isolated from fungi (e.g. Acremonium chrysogenum, Penicillium chrysogenum and Aspergillus nidulans) and bacteria (e.g. Streptomyces clavuligerus). We have shown that botanical extracts prepared from Larrea tridentata have strong antimicrobial activity against several bacteria, including members of Staphylococcus and Streptococcus genera.

Methods

Through resistance studies, inhibitor assays, and ELISA testing, we demonstrated L. tridentata extracts may contain a β-lactam type antibiotic activity.

Results

Based on the estimated β-lactam concentration within the extract, the antimicrobial activity of the L. tridentata extract was approximately 2000–8000-fold greater against Staphylococcus as compared to other β-lactams, penicillin or ampicillin. In the L. tridentata extract, this increased activity was found to be associated with the likely presence of a cofactor leading to increased potentiation of the β-lactam activity. This potentiation activity was also observed to enhance the activity of exogenously added natural penicillin antibiotics.

Conclusions

Although constituents were not isolated in this study, the results obtained strongly support the presence of β-lactam type antibiotic activity and antibiotic potentiation activity present in ethanolic extracts prepared from L. tridentata.
A description of the relationship in healthy longevity and aging-related disease: from gene to protein
Authors: Ni Xiaolin , Wang Zhaoping , Gao Danni , Yuan Huiping , Sun Liang , Zhu Xiaoquan , Zhou Qi , Yang Ze
Published: June 2021

Human longevity is a complex phenotype influenced by both genetic and environmental factors. It is also known to be associated with various types of age-related diseases, such as Alzheimer’s disease (AD) and cardiovascular disease (CVD). The central dogma of molecular biology demonstrates the conversion of DNA to RNA to the encoded protein. These proteins interact to form complex cell signaling pathways, which perform various biological functions. With prolonged exposure to the environment, the in vivo homeostasis adapts to the changes, and finally, humans adopt the phenotype of longevity or aging-related diseases. In this review, we focus on two different states: longevity and aging-related diseases, including CVD and AD, to discuss the relationship between genetic characteristics, including gene variation, the level of gene expression, regulation of gene expression, the level of protein expression, both genetic and environmental influences and homeostasis based on these phenotypes shown in organisms.
Amphibian breeding phenology influences offspring size and response to a common wetland contaminant
Authors: Buss Nicholas , Swierk Lindsey , Hua Jessica
Published: June 2021

Background

Increases in temperature variability associated with climate change have critical implications for the phenology of wildlife across the globe. For example, warmer winter temperatures can induce forward shifts in breeding phenology across taxa (“false springs”), which can put organisms at risk of freezing conditions during reproduction or vulnerable early life stages. As human activities continue to encroach on natural ecosystems, it is also important to consider how breeding phenology interacts with other anthropogenic stressors (e.g., pollutants). Using 14 populations of a widespread amphibian (wood frog;Rana sylvatica), we compared 1) growth; 2) tolerance to a common wetland contaminant (NaCl); and 3) the ability of tadpoles to acclimate to lethal NaCl exposure following sublethal exposure earlier in life. We evaluated these metrics across two breeding seasons (2018 and 2019) and across populations of tadpoles whose parents differed in breeding phenology (earlier- versus later-breeding cohorts). In both years, the earlier-breeding cohorts completed breeding activity prior to a winter storm and later-breeding cohorts completed breeding activities after a winter storm. The freezing conditions that later-breeding cohorts were exposed to in 2018 were more severe in both magnitude and duration than those in 2019.

Results

In 2018, offspring of the later-breeding cohort were larger but less tolerant of NaCl compared to offspring of the earlier-breeding cohort. The offspring of the earlier-breeding cohort additionally were able to acclimate to a lethal concentration of NaCl following sublethal exposure earlier in life, while the later-breeding cohort became less tolerant of NaCl following acclimation. Interestingly, in 2019, the warmer of the two breeding seasons, we did not detect the negative effects of later breeding phenology on responses to NaCl.

Conclusions

These results suggest that phenological shifts that expose breeding amphibians to freezing conditions can have cascading consequences on offspring mass and ability to tolerate future stressors but likely depends on the severity of the freeze event.
Prolonged exposure to traffic-related particulate matter and gaseous pollutants implicate distinct molecular mechanisms of lung injury in rats
Authors: Jheng Yu-Teng , Putri Denise Utami , Chuang Hsiao-Chi , Lee Kang-Yun , Chou Hsiu-Chu , Wang San-Yuan , Han Chia-Li
Published: June 2021

Background

Exposure to air pollution exerts direct effects on respiratory organs; however, molecular alterations underlying air pollution-induced pulmonary injury remain unclear. In this study, we investigated the effect of air pollution on the lung tissues of Sprague-Dawley rats with whole-body exposure to traffic-related PM1 (particulate matter < 1 μm in aerodynamic diameter) pollutants and compared it with that in rats exposed to high-efficiency particulate air–filtered gaseous pollutants and clean air controls for 3 and 6 months. Lung function and histological examinations were performed along with quantitative proteomics analysis and functional validation.

Results

Rats in the 6-month PM1-exposed group exhibited a significant decline in lung function, as determined by decreased FEF25–75% and FEV20/FVC; however, histological analysis revealed earlier lung damage, as evidenced by increased congestion and macrophage infiltration in 3-month PM1-exposed rat lungs. The lung tissue proteomics analysis identified 2673 proteins that highlighted the differential dysregulation of proteins involved in oxidative stress, cellular metabolism, calcium signalling, inflammatory responses, and actin dynamics under exposures to PM1 and gaseous pollutants. The presence of PM1 specifically enhanced oxidative stress and inflammatory reactions under subchronic exposure to traffic-related PM1 and suppressed glucose metabolism and actin cytoskeleton signalling. These factors might lead to repair failure and thus to lung function decline after chronic exposure to traffic-related PM1. A detailed pathogenic mechanism was proposed to depict temporal and dynamic molecular regulations associated with PM1- and gaseous pollutants-induced lung injury.

Conclusion

This study explored several potential molecular features associated with early lung damage in response to traffic-related air pollution, which might be used to screen individuals more susceptible to air pollution.
Comparison of denosumab and zoledronic acid for the treatment of solid tumors and multiple myeloma with bone metastasis: a systematic review and meta-analysis based on randomized controlled trials
Authors: Jiang Lianghai , Cui Xianghua , Ma Haoning , Tang Xiangsheng
Published: June 2021

Objective

To compare the efficacy and safety between denosumab and zoledronic acid for advanced cancer with bone metastasis.

Methods

MEDLINE, EMBASE, and the Cochrane library databases were searched for randomized controlled trials up to December 2020 that compared denosumab and zoledronic acid in the treatment of advanced cancer with bone metastasis. The following clinical outcomes were extracted for analysis: time to first skeletal-related event, time to first-and-subsequent skeletal-related events, overall survival, and disease progression. Safety outcomes including incidence of adverse events, serious adverse events, acute-phase reactions, renal toxicity, osteonecrosis of the jaw, and hypocalcemia were also extracted.

Results

Four randomized controlled trials involving 7201 patients were included. The overall analysis showed that denosumab was superior to zoledronic acid in delaying time to first skeletal-related event (hazard ratio = 0.86; 95% confidence interval, 0.80–0.93; P < 0.01) and time to first-and-subsequent skeletal-related events (risk ratio 0.87; 95% confidence interval 0.81–0.93; P < 0.01). Denosumab was associated with lower incidence of renal toxicity (risk ratio 0.69; 95% confidence interval 0.54–0.87; P < 0.01) and acute phase reaction (risk ratio 0.47; 95% confidence interval 0.38–0.56; P < 0.01), but higher incidence of hypocalcemia (risk ratio 1.78; 95% confidence interval 1.33–2.38; P < 0.01) and osteonecrosis of the jaw (risk ratio 1.41; 95% confidence interval 1.01–1.95; P = 0.04). No significant differences were found in overall survival, time to disease progression, or incidence of adverse events and serious adverse events between denosumab and zoledronic acid.

Conclusions

Compared with zoledronic acid, denosumab is associated with delayed first-and-subsequent skeletal-related events, lower incidence of renal toxicity, and acute phase reaction, but higher incidence of hypocalcemia and osteonecrosis of the jaw. Hence, denosumab seems to be a promising choice for advanced cancer with bone metastasis. Nonetheless, more randomized controlled trials are needed for further evaluation.
The effect of phased written health education combined with healthy diet on the quality of life of patients after heart valve replacement
Authors: Li Dan , Liu Pujuan , Zhang Huijun , Wang Li
Published: June 2021

Background

To observe the effect of phased written health education combined with healthy diet on the quality of life of patients after heart valve replacement.

Methods

One hundred-thirty patients who underwent heart valve replacement surgery in our hospital from January 2018 to January 2020 were enrolled as the research subjects. They were randomly divided into study group (65 patients, phased written health education combined with health Diet) and control group (65 cases, routine health education). The drug compliance and the degree of anticoagulant drugs knowledge were compared between the two groups in the first and second stage rehabilitation and the recovery stage. The health behavior ability and quality of life at different phases were also observed.

Results

During the first and the second stage rehabilitation, and the recovery stage, the drug compliance of the study group was superior to that of the control group, with statistical significance (P < 0.05). Meanwhile, the knowledge of anticoagulant drugs in the study group was better than that in the control group, with statistical significance (P < 0.05). Before intervention, there was no significant difference in health behavior ability and quality of life between the two groups (P > 0.05). The healthy behavior ability of study group for each stage was superior to the control group, the difference was significant (P < 0.05). The healthy behavior ability and quality of life showed the same results with statistical significance (P < 0.05).

Conclusion

The use of phased written health education combined with healthy diet in patients after heart valve replacement can effectively improve patients’ medication compliance, anticoagulant drugs knowledge, healthy behavior ability and quality of life at different stages, and is worthy of clinical application.
Predictors of time-to-death on children in Tigray regional state, Ethiopia: a retrospective cross sectional study
Authors: Gebrerufael Gebru Gebremeskel , Hagos Bsrat Tesfay
Published: June 2021

Background

Although, the clinical and socioeconomic condition of Tigray Regional State mothers has been improved along with the decline in the child death rate. However, children’s death rate is still one of the main community serious challenging issues of public health concern. Thus, the main objective of this current investigation was to identify the major predictor factors for short time-to-death in Children in the Tigray Regional State.

Methods

The study used a secondary data with cross-sectional study design.

The information gathered was from 1018 childbirths 5 years prior to the survey. Independent variables such as mother’s demographic variables, child demographic variables, healthiness and environmental factors were considered major hazard predictors of children’s short time-to-death rate. This current investigation used bivariable and multivariable Cox regression model analysis to identify the major statistically significant associations with children’s time-to-death rate.

Results

One thousand eighteen children under 5 years of age were included in the study.

Of them, 50% of the children were males, and the median survival time-to-death of children was 26 months.

Overall, the prevalence of experiencing child’s death rate in the Tigray Regional State was 4.2%.

The multivariable Cox regression model analysis showed that living rural place of residence (AHR = 19.8; 95% CI: (7.25–54.049)), being unvaccinated child (no) (AHR = 2.76; 95% CI: (1.071–7.11)), and poor wealth index (AHR = 15.4; 95% CI: (2.83–84)) were statistically significant predictors of time-to-death rate of children’s.

Conclusion

The study recognized that being a rural place of residence, unvaccinated child status (no) and poor wealth index were statistically significant predictors of children’s short time-to-death rate.
The ancient koji mold (Aspergillus oryzae) as a modern biotechnological tool
Authors: Daba Ghoson M. , Mostafa Faten A. , Elkhateeb Waill A.
Published: June 2021

Aspergillus oryzae (A. oryzae) is a filamentous micro-fungus that is used from centuries in fermentation of different foods in many countries all over the world. This valuable fungus is also a rich source of many bioactive secondary metabolites. Moreover, A. oryzae has a prestigious secretory system that allows it to secrete high concentrations of proteins into its culturing medium, which support its use as biotechnological tool in veterinary, food, pharmaceutical, and industrial fields. This review aims to highlight the significance of this valuable fungus in food industry, showing its generosity in production of nutritional and bioactive metabolites that enrich food fermented by it. Also, using A. oryzae as a biotechnological tool in the field of enzymes production was described. Furthermore, domestication, functional genomics, and contributions of A. oryzae in functional production of human pharmaceutical proteins were presented. Finally, future prospects in order to get more benefits from A. oryzae were discussed.
Electronic cigarette and cannabis use: results from the 2018 Maryland Youth Risk Behavior Survey
Authors: Luken Amanda , Thrul Johannes , Johnson Renee M.
Published: June 2021

Objective

To determine the relationship between lifetime e-cigarette use and current cannabis use among youth. Our analyses accounted for county variability, in addition to student-level covariates.

Methods

This study examined responses from high school students on a state-level population survey, the 2018 Maryland Youth Risk Behavior Survey/Youth Tobacco Survey, a cross-sectional, complex survey sample. Of participating students, final analyses included an unweighted sample of 41,091 9th to 12th grade students who provided complete reports for measured variables. Analyses with survey weights were conducted between August 2019 and May 2020. A multivariable logistic regression was conducted to investigate the association between lifetime e-cigarette use and current (past 30-day) cannabis use, after controlling for county, lifetime cigarette use, current (past 30-day) alcohol use, emotional distress, and demographics.

Results

Lifetime e-cigarette use significantly increased the odds of current cannabis use among Maryland high school students (aOR = 6.04; 95% CI 5.27, 6.93). Other significant risk factors for current cannabis use included lifetime cigarette use (aOR 2.23, 95% CI 1.86, 2.68) and current alcohol use (aOR 5.21, 95% CI 4.42, 6.14). Significantly higher odds of current cannabis use were also found among older high school students, males, non-Hispanic Blacks and students identifying as other race, and those reporting emotional distress.

Conclusions

Lifetime e-cigarette use among Maryland high school students is strongly associated with current cannabis use when including counties as a covariate. Non-significant county differences, however, suggest smaller geographical units may be required to control for variability. Efforts should focus on reducing youth e-cigarette use to decrease cannabis use. Maryland’s recent implementation of Tobacco 21 and a ban on flavored e-cigarettes will be of interest for future evaluations.
Study of hepatitis B virus infection, reactivation among patients with chronic hepatitis C infection treated by direct antiviral agents (DAAs)
Authors: Azeem Haitham A. , Alkabeer Ashraf M. , Mohammed Ali Sobhy , Hussein Amira Ahmed
Published: June 2021

Background

Hepatitis B virus (HBV) may reactivate when treating chronic hepatitis C (CHC) with direct-acting antivirals (DAA). We aimed to investigate the risk of HBV infection and reactivation during DAA therapy by performing a prospective observational study carried on 200 patients positive for chronic HCV who were candidates for treatment by DAA therapy according to the Egyptian guidelines from February 2019 to December 2019; the patients identified to carry HBsAg at baseline or with positive HBc Abs were further assessed for other HBV markers: hepatitis B e antigen at baseline, and serum HBV DNA quantitative measurement at baseline, week 4 of treatment, end of treatment. On the other hand, recent infection by HBV among those patients was observed.

Results

Of all participants, 49% were males and 51% were females, aged above 18 years. There is a highly statistically significant difference (p-value < 0.05) between HCV RNA PCR (at the beginning, at the end of 4 weeks, and at the end of 12 weeks) in studied patients. There was a highly statistically significant difference found between the liver function tests at the beginning, at the end of 4 weeks, and at the end of 12 weeks of treatment where it shows improvement except for serum albumin. At beginning of the study, there were 34 patients who are co-infected with HCV and HBV with quantitative PCR test for HBV DNA ≥ 20 IU/ml. After 1 month of DAA therapy, reactivation was detected in 6 cases (4 occult cases show reverse seroconversion (became HBs Ag positive), and 2 co-infected cases show increased HBV DNA > 1000 IU/L above the baseline level). In addition, 3 new cases acquired recent infection with the positivity of HBc IgM and detectable levels of HBV DNA. After 3 months of study, reactivation was detected in one patient with co-infection (where increased HBV DNA > 1000 IU/L above the baseline level), and 5 new cases acquired recent infection late in the study.

Conclusion

Screening for HBV infection prior to DAA therapy is required to detect recent infection of reactivation of previous infection during or after DAA therapy.
Effects of Proton Pump Inhibitors on Glycemic Control and Incident Diabetes: A Systematic Review and Meta-analysis
Authors: Peng Carol Chiung-Hui , Tu Yu-Kang , Lee Gin Yi , Chang Rachel Huai-En , Huang Yuting , Bukhari Khulood , Tsai Yao-Chou , Fu Yunting , Huang Huei-Kai , Munir Kashif M
Published: June 2021

Context

Whether proton pump inhibitors (PPI) can improve glycemic control among individuals with diabetes or decrease the risk of incident diabetes in the general population is unclear.

Objective

To evaluate the impact of PPI therapy on glycemic control among individuals with diabetes and the risk of diabetes among those without diabetes.

Results

PubMed, Embase, Scopus, and ClinicalTrials.gov were searched from inception to November 21, 2020. We included studies comparing glycosylated hemoglobin (HbA1c) or fasting blood glucose (FBG) among individuals with diabetes treated with and without PPI therapy as an add-on to standard therapy. Studies evaluating the risk of incident diabetes among individuals taking PPI were assessed. We performed dual independent review, data extraction, and quality assessment. Weighted mean differences between groups or relative risks were imputed using random-effects models.

Results

Seven studies (n = 342) for glycemic control and 5 studies (n = 244 439) for risk of incident diabetes were included. Compared with standard therapy, add-on PPI was associated with a significant decrease in HbA1c (WMD, −0.36 %; 95% CI, −0.68 to −0.05; P = 0.025) and FBG (WMD, −10.0 mg/dL; 95% CI, −19.4 to −0.6; P = 0.037). PPI use did not reduce the risk of incident diabetes (pooled RR, 1.10; 95% CI, 0.89 to 1.34; P = 0.385).

Conclusion

Add-on PPI improved glycemic indices among individuals with diabetes but did not alter the risk of incident diabetes. The effects of PPI on glycemic control should be considered when prescribing antacids to patients with diabetes.
Synthesis of First Antimony Porphycene and Electrocatalytic Hydrogen Evolution Driven by Ligand-Centered Reduction
Authors: Zhang Zhi , Fujioka Taro , Koide Taro , Yano Yoshio , Ono Toshikazu , Hisaeda Yoshio
Published: June 2021

For post-transition metal electrocatalytic hydrogen evolution reaction (HER), the new porphycene antimony complexes, Sb(III)OEPo and Sb(V)OEPo-Br2, were synthesized and characterized. Based on the electrochemical and electro-spectro measurements, the two-step one-electron reduction processes of Sb(III)OEPo were indicated to be both ligand-centered and the irreversible reduction process observed for Sb(V)OEPo-Br2 was assigned to be the reduction from Sb(V)OEPo-Br2 to Sb(III)OEPo. Electrocatalytic HER proceeded at −1.0 V (vs. Ag/AgCl) under acidic conditions via the ligand-centered reductions. The electron accepting nature of the porphycene ligand enabled the utilization of a main-group element as a central element for the ligand-centered HER at anodically shifted potentials.