bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of an individualised exercise programme plus Behavioural Change Enhancement (BCE) strategies for managing fatigue in frail older adults: a cluster randomised controlled trial
Authors: Liu Justina Y. W. , Yin Yue-Heng , Kor Patrick P. K. , Kwan Rick Y. C. , Lee Paul H. , Chien Wai Tong , Siu Parco M. , Hill Keith D.
Published: June 2023

Background

To the best of our knowledge, although ageing-induced fatigue could cause adverse outcomes such as frailty, there is currently no intervention for it. This study evaluated the effects of an individualised exercise programme with/without BCE strategies on reducing fatigue in older adults.

Methods

A three-armed cluster-randomised controlled trial (RCT) was conducted with 184 participants (mean age: 79.1 ± 6.4; mean frailty score: 2.8 + 0.8) from 21 community centres (ClinicalTrials.gov: NCT03394495). They were randomised into either: the COMB group (n = 64), receiving 16 weeks of exercise training plus the BCE programme; the EXER group (n = 65), receiving exercise training and health talks; or the control group (n = 55), receiving only health talks. Fatigue was assessed using the Multi-dimensional Fatigue Inventory (range: 20 to 100, with higher scores indicating higher fatigue levels) at baseline, and immediately, 6 months, and 12 months post-intervention.

Results

The GEE analyses showed significant interaction (time x group) between the COMB and control groups immediately (p < 0.001), 6 months (p < 0.001), and 12 months (p < 0.001) post-intervention. Comparing the COMB and EXER groups, there was a significant interaction immediately (p = 0.013) and at 12 months post-intervention (p = 0.007). However, no significant difference was seen between the EXER group and control group at any time point.

Conclusions

The COMB intervention showed better immediate and sustainable effects (i.e., 12 months after the intervention) on reducing fatigue in frail older adults than exercise training or health education alone.

Trial registration

ClinicalTrials.gov (NCT03394495), registered on 09/01/2018.
The L-shaped correlation between systolic blood pressure and short-term and long-term mortality in patients with cerebral hemorrhage
Authors: Xu Jiang , Xie Zhiping , Chen Kang , Lan Shihai , Liao Gang , Xu Shan , Yang Xuanyong , Luo Hai
Published: June 2023

Background

A large amount of evidence has shown the necessity of lowering blood pressure (BP) in patients with acute cerebral hemorrhage, but whether reducing BP contributes to lower short-term and long-term mortality in these patients remains uncertain.

Aims

We aimed to explore the association between BP, including systolic and diastolic BP, during intensive care unit (ICU) admission and 1-month and 1-year mortality after discharge of patients with cerebral hemorrhage.

Methods

A total of 1085 patients with cerebral hemorrhage were obtained from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Maximum and minimum values of systolic and diastolic BP in these patients during their ICU stay were recorded, and endpoint events were defined as the 1-month mortality and 1-year mortality after the first admission. Multivariable adjusted models were performed for the association of BP with the endpoint events.

Results

We observed that patients with hypertension were likely to be older, Asian or Black and had worse health insurance and higher systolic BP than those without hypertension. The logistic regression analysis showed inverse relationships between systolic BP-min (odds ratio (OR) = 0.986, 95% CI 0.983–0.989, P < 0.001) and diastolic BP-min (OR = 0.975, 95% CI 0.968–0.981, P < 0.001) and risks of 1-month, as well as 1-year mortality when controlling for confounders including age, sex, race, insurance, heart failure, myocardial infarct, malignancy, cerebral infarction, diabetes and chronic kidney disease. Furthermore, smooth curve analysis suggested an approximate L-shaped association of systolic BP with the risk of 1-month mortality and 1-year mortality. Reducing systolic BP in the range of 100–150 mmHg has a lower death risk in these patients with cerebral hemorrhage.

Conclusion

We observed an L-shaped association between systolic BP levels and the risks of 1-month and 1-year mortality in patients with cerebral hemorrhage, which supported that lowering BP when treating an acute hypertensive response could reduce short-term and long-term mortality.
Development and internal validation of a non-invasive clinical tool to predict sufficient omega-3 levels in early pregnancy
Authors: Fu Joanna YX , Wang Carol A , Liu Ge , Mead Elyse , Phung Jason , Makrides Maria , Pennell Craig E
Published: June 2023

Background

Complications from preterm birth (PTB) are the leading cause of death and disability in those under five years. Whilst the role of omega-3 (n-3) supplementation in reducing PTB is well-established, growing evidence suggests supplementation use in those replete may increase the risk of early PTB. Aim: To develop a non-invasive tool to identify individuals with total n-3 serum levels above 4.3% of total fatty acids in early pregnancy.

Methods

We conducted a prospective observational study recruiting 331 participants from three clinical sites in Newcastle, Australia. Eligible participants (n = 307) had a singleton pregnancy between 8 and 20 weeks’ gestation at recruitment. Data on factors associated with n-3 serum levels were collected using an electronic questionnaire; these included estimated intake of n-3 (including food type, portion size, frequency of consumption), n-3 supplementation, and sociodemographic factors. The optimal cut-point of estimated n-3 intake that predicted mothers with total serum n-3 levels likely above 4.3% was developed using multivariate logistic regression, adjusting for maternal age, body mass index, socioeconomic status, and n-3 supplementation use. Total serum n-3 levels above 4.3% was selected as previous research has demonstrated that mothers with these levels are at increased risk of early PTB if they take additional n-3 supplementation during pregnancy. Models were evaluated using various performance metrics including sensitivity, specificity, area under receiver operator characteristic (AUROC) curve, true positive rate (TPR) at 10% false positive rate (FPR), Youden Index, Closest to (0,1) Criteria, Concordance Probability, and Index of Union. Internal validation was performed using 1000-bootstraps to generate 95% confidence intervals for performance metrics generated.

Results

Of 307 eligible participants included for analysis, 58.6% had total n-3 serum levels above 4.3%. The optimal model had a moderate discriminative ability (AUROC 0.744, 95% CI 0.742–0.746) with 84.7% sensitivity, 54.7% specificity and 37.6% TPR at 10% FPR.

Conclusions

Our non-invasive tool was a moderate predictor of pregnant women with total serum n-3 levels above 4.3%; however, its performance is not yet adequate for clinical use.

Trial registration

This trial was approved by the Hunter New England Human Research Ethics Committee of the Hunter New England Local Health District (Reference 2020/ETH00498 on 07/05/2020 and 2020/ETH02881 on 08/12/2020).
Factors influencing the free maternal health care policy under the national health insurance scheme’s provision for skilled delivery services in Ghana: a narrative literature review
Authors: Abredu Juliet , Alipitio Boo , Dwumfour Catherine K. , Witter Sophie , Dzomeku Veronica Millicent
Published: June 2023

Background

Skilled Birth Attendance (SBA) is important in achieving the Sustainable Development Goals (SDGs) targets 3.1, 3.2 and 3.3.1. Ghana has made steady progress in SBA, yet, unsupervised deliveries still occur. The introduction of the Free Maternal Health Care Policy under the National Health Insurance Scheme (FMHCP under the NHIS) has improved the uptake of SBA but with some implementation challenges. This narrative review sought to explore the factors influencing the FMHCP under the NHIS provision for skilled delivery services in Ghana.

Methods

Electronic searches were conducted of databases including PubMed, Popline, Science direct, BioMed Central, Scopus and Google scholar for peer reviewed articles as well as grey articles from other relevant sources, published between 2003 and 2021 on factors influencing FMHCP/NHIS provision for skilled delivery services in Ghana. Keywords used in the literature search were in various combinations for the different databases. The articles were screened to determine the inclusion and exclusion criteria and quality was assessed using a published critical appraisal checklist. A total of 516 articles were retrieved for initial screening based on their titles, of which 61 of them, were further screened by reading their abstracts and full text. Of this number, 22 peer-reviewed and 4 grey articles were selected for the final review based on their relevance.

Results

The study revealed that the FMHCP under the NHIS does not cover the full costs associated with skilled delivery and low socioeconomic status of households affects SBA. Also, funding and sustainability, hinders the quality-of-service delivery offered by the policy.

Conclusion

For Ghana to achieve the SDGs above and further improve SBA, the cost associated with skilled delivery should be fully covered by the NHIS. Also, the government and the key stakeholders involved in the policy implementation, must put in place measures that will enhance the operation and the financial sustainability of the policy.
RETRACTED ARTICLE: Predictors of depression among school adolescents in Northwest, Ethiopia, 2022: institutional based cross-sectional
Authors: Chekol Aklile Tsega , Wale Mastewal Aschale , Abate Agmas Wassie , Beo Eyerusalem Abebe , Said Eman Ali , Negash Berhan Tsegaye
Published: June 2023

Background

Adolescent depression is a serious mental disorder that makes family problems, learning challenges, drug addiction, and increases absenteeism from school. It also has a major impact on a person’s ability to manage his or her daily tasks. In the end, the condition may result in self-destruction. Research is scarce among high schools in the study setting. Therefore, this study aimed to assess the prevalence and its associated factors of depression among high school adolescent students in Bahirdar City, Northwest Ethiopia in 2022.

Methods

An institutional-based cross-sectional study was done from June 18 to July 16, 2022, among public and private high school adolescent students in Bahir Dar City, Amhara region, Ethiopia. A two-stage sampling technique was utilized. First, stratification by school type was made and schools were selected 30–40% by using a simple random sampling technique. Finally, an updated sampling frame was taken from each school director to select a sample of 584 study participants after proportional allocation by simple random sampling from six high schools. Patient Health Questionnaires were used to assess depression in high school students. The independent variables, like substance-related factors, were assessed by yes-or-no questions, and the academic stressor by academic stress in secondary education, was assessed by structured questionnaires. Binary and multivariate logistic regressions were used to identify factors associated with depression. Statistical significance was declared at a 95% confidence interval when the value of p was less than or equal to 0.05.

Results

The response rate of the participants was 96.9%. The overall magnitude of adolescent depression was found to be 22.1% (95%CI 18.7, 25.7%). Being female (AOR: 3.43; 95%CI 2.11, 5.56), small family size (AOR: 3.01; 95%CI 1.47, 6.15); ever alcohol use (AOR: 2.40; 95%CI 1.51, 3.81); attending a public school (AOR: 3.01; 95%CI 1.68, 5.40), and having a history of abuse (AOR: 1.92; 95%CI 2.2, 3.08) were associated with depression.

Conclusion

In this study, the magnitude of depression among high school students in Bahir Dar City was higher than the national threshold. There was a significant association between sex, family size of parents, ever alcohol use, public schools, and having a history of abuse with depression among adolescents. Hence, it is better for schools to screen and provide intervention for depression in public high school students and offer therapies, especially in females and those with a history of abuse, small family size, or alcohol use.
Psychometric properties of an Arabic translation of the multidimensional social support scale (MSPSS) in a community sample of adults
Authors: Fekih-Romdhane Feten , Fawaz Mirna , Hallit Rabih , Sawma Toni , Obeid Sahar , Hallit Souheil
Published: June 2023

Background

There is a lack of methodologically strong measure to assess perceived social support among Arabic-speaking populations. Our main objective was therefore to examine the psychometric properties of an Arabic translation of the Multidimensional Social Support Scale (MSPSS) in a sample of Arabic-speaking Lebanese adults from the general population.

Methods

We adopted a cross-sectional design involving a convenience sample of 387 non-clinical Lebanese adults aged 26.17 ± 11.47 years (58.4% females). Participants were administered a web-based anonymous questionnaire containing the MSPSS, the 10-item Connor-Davidson Resilience Scale, and the Post traumatic growth Inventory-Short Form. The forward-backward translation method was applied. Confirmatory factor analysis (CFA) and gender invariance in the MSPSS were examined. McDonald’s ω coefficients were calculated as internal consistency indicators.

Results

The Arabic MSPSS and its subscales have a high internal consistency with McDonald’s ω values between 0.94 and 0.97. CFA indicated that fit of the three-factor model was acceptable. All indices suggested that configural, metric, and scalar invariance was supported across gender. Both genders exhibited no significant difference in all MSPSS dimensions. Convergent validity was supported by showing that all three MSPSS sub-scores and total score correlated significantly and positively with resilience and posttraumatic growth scores.

Conclusion

Although further cross-cultural validations involving other Arab countries and communities are still needed, we preliminarily suggest that this scale is applicable to the broad Arabic-speaking people for the measurement of perceived social support in clinical and research contexts.
The effect of a course of selected corrective exercises on posture, scapula-humeral rhythm and performance of adolescent volleyball players with upper cross syndrome
Authors: Firouzjah Morteza Homayounnia , Firouzjah Ebrahim Mohammad Ali Nasab , Ebrahimi Zahra
Published: June 2023

Background

This study aims to investigate the effect of a course of selected corrective exercises on posture, scapula-humeral rhythm and performance of adolescent volleyball players.

Methods

30 adolescent volleyball players with upper cross syndrome were purposefully selected and assigned into 2 control and training groups. The degree of back curvature was evaluated using a flexible ruler, forward head and forward shoulder size by photographic method, scapula-humeral rhythm by Lateral Scapular Slide Test (LSST), and performance by closed kinetic chain test. The training group performed the exercises for 10 weeks. After the exercises, the post-test was administered. To analyze the data, analysis of co-variance tests and paired t-test at the level of 0.05 were employed.

Results

The research results showed that corrective exercises have a significant effect on abnormalities of forward head, forward shoulder, kyphosis, scapula-humeral rhythm and performance.

Conclusions

Corrective exercises can be effective in reducing shoulder girdle and spine abnormalities and improving scapula- humeral rhythm and performance of volleyball players.
The effect of scanning pathways on trueness and precision in full-arch optical impression
Authors: Kuroda Shota , Yotsuya Mamoru , Sato Toru , Hisanaga Ryuichi , Nomoto Syuntaro , Sekine Hideshi
Published: June 2023

Background

In this study, we investigated the effects of differences in scanning pathways during optical impression on the trueness and precision of full-arch impressions.

Methods

Reference data were obtained using a laboratory scanner. All optical impressions were measured across the dental arch using TRIOS® 3 in four different pathways. The reference and optical impression data were superimposed using the best-fit method. The criteria for superimposition were based on the starting side of the dental arch (partial arch best-fit method, PB) and based on the full arch (full arch best-fit method, FB). The data were compared between the left and right molars (starting and ending sides). The scan deviations for trueness (n = 5) and precision (n = 10) were obtained for each group by calculating the root mean square (RMS) of the deviation at each measurement point. Visual observations using superimposed color map images revealed variations in trueness.

Results

There were no significant differences in scanning time or amount of scan data between the four scanning pathways. Trueness did not differ significantly among the four pathways with respect to the starting and ending sides, regardless of the superimposition criteria. Precision with PB was significantly different between scanning pathways A and B, and pathways B and C for the starting sides, and between scanning pathways A and B, and pathways A and D for the ending sides. In contrast, there was no significant difference between the starting and ending side in pathways for FB. Regarding PB, color map images showed a large error range in the direction toward the molar radius for the occlusal surface and cervical regions on the ending sides.

Conclusion

Differences in the scanning pathways did not affect trueness, regardless of the superimposition criteria. On the other hand, differences in the scanning pathways affected the precision of the starting and ending sides with PB. Scanning pathways B and D were more precise on the starting and ending sides, respectively.
Exploring the role of ICT in pharmaceutical supply chain practices and operational performance in Ethiopia: a structural equation modeling approach
Authors: Hailu Rabira , Gizaw Tafesse , Berhanu Nimona , Mulugeta Tidenek , Boche Bekele , Gudeta Tadesse
Published: June 2023

Background

A well-coordinated supply chain ensures the sustainable availability of life-saving medicines that improve public health outcomes. Information Communication Technology (ICT) is one of the strategies for optimizing supply chain coordination. However, there is a paucity of data on how it affects supply chain practice and performance at the Ethiopian Pharmaceutical Supply Agency (EPSA).

Objective

This study aimed to explore the relationships between information and communication technology, supply chain practice, and pharmaceutical supply chain operational performance using a structural equation modeling approach.

Methods

We conducted an analytical cross-sectional study between April and June 2021. Three hundred twenty EPSA employees participated in the survey. We used a pretested, self-administered five-point Likert scale questionnaire to collect the intended data. A structural equation modeling confirmed the relationship between the constructs (information communication technology, supply chain practices, and performance). Thus, the measurement models were first validated using exploratory and confirmatory factor analysis in SPSS/AMOS software. A p-value of less than 5% indicated statistical significance.

Results

Of the 320 questionnaires distributed, 300 participants (202 males and 98 females) duly responded. In this survey, supply chain practices (mainly customer relationship management and information sharing) and ICT had significant positive direct effects on operational performance with standardized regression weights (β) of 0.65 (p < .001) and 0.29 (p < .001), respectively. On the other hand, 73% of the variations in operational performance were explained by ICT and supply chain practices, wherein ICT played moderate mediation effects between supply chain practice and performance (VAF = 0.24, p < .001). Despite the significant positive influence of ICT, the agency still faced data visibility problems with customers and other supply chain partners.

Conclusion

The findings revealed that supply chain practices and ICT implementation impacted the agency’s supply chain performance positively and significantly. The ICT implementation practice in the agency posited a significant positive partial mediating role between supply chain practice and operational performance. Thus, if the agency focuses on the automation and integration of customer relationship management and the practice of information exchange, the essential supply chain practices, it can further improve operational performance.
Differences in medical costs between TCM users and TCM nonusers in inpatients with thalassemia
Authors: Han Zhaoran , Nie Hanlin , Huang Zhengwei , Tuo Zegui , Chen Sisi , Ma Yong , Shi Xuefeng
Published: June 2023

Background

Thalassemia has brought serious health threats and economic burdens to patients worldwide. There is no sovereign remedy for thalassemia, both conventional and Traditional Medicine (TM) methods have certain effects on this disease. As typical of TM, Traditional Chinese Medicine (TCM) has been widely used in the treatment of thalassemia. Previous studies mainly focused on conventional treatments for thalassemia and patients’ medical burden, but no research has examined the effects of TCM use on the economic burdens for thalassemia inpatients in mainland China. The main objective of this study is to compare the medical cost differences between TCM users and TCM nonusers, furtherly, we will discuss the role of TCM use in the treatment of thalassemia.

Methods

We employed the 2010–2016 Medicare claims database provided by the China Health Insurance Research Association (CHIRA). Chi-square and Mann-Whitney tests were used to analyze the differences between TCM users and TCM nonusers. Multiple regression analysis was performed using the ordinary least squares method to compare the TCM users’ inpatient medical cost with TCM nonusers’, and to further examine the correlation between TCM cost, conventional medication cost and nonpharmacy cost for TCM users.

Results

A total of 588 urban thalassemia inpatients were identified, including 222 TCM users and 366 TCM nonusers. The inpatient medical cost of TCM users was RMB10,048 (USD1,513), which was significantly higher than TCM nonusers (RMB1,816 (USD273)). Total inpatient cost for TCM users was 67.4% higher than those of TCM nonusers (P < 0.001). With confounding factors fixed, we found that the conventional medication cost and nonpharmacy cost were positively correlated with TCM cost.

Conclusion

Total hospitalization expenses for TCM users were higher than TCM nonusers. Both the conventional medication cost and nonpharmacy cost of TCM users were all higher than TCM nonusers. We infer TCM plays a complementary role, rather than an alternative, in the treatment of thalassemia due to the lack of cooperative treatment guidelines. It is recommended that a cooperative diagnosis and treatment guidelines should be generated to balance the use of TCM and conventional medicine for treating thalassemia, so as to reduce the economic burdens on patients.
Engineering of cyclodextrin glycosyltransferase improves the conversion efficiency of rebaudioside A to glucosylated steviol glycosides and increases the content of short-chain glycosylated steviol glycoside
Authors: Zhang Ruiqin , Tang Ruiqi , Wang Wei , Bi Jiahua , Xu Xianrui , Fan Qiuling , Li Yanjun , Chen Qihe
Published: June 2023

Background

Compared with steviol glycosides, the taste of glucosylated steviol glycosides is better and more similar to that of sucrose. At present, cyclodextrin glucanotransferase (CGTase) is primarily used to catalyze the conversion of steviol glycosides to glucosylated steviol glycosides, with soluble starch serving as a glycosyl donor. The main disadvantages of enzymatic transglycosylation are the limited number of enzymes available, the low conversion rates that result in low yields, and the lack of selectivity in the degree of glycosylation of the products. In order to fill these gaps, the proteome of Alkalihalobacillus oshimensis (also named Bacillus oshimensis) was used for mining novel CGTases.

Results

Here, CGTase-15, a novel β-CGTase with a wide pH adaptation range, was identified and characterized. The catalyzed product of CGTase-15 tasted better than that of the commercial enzyme (Toruzyme® 3.0 L). In addition, two amino acid sites, Y199 and G265, which play important roles in the conversion of steviol glycosides to glucosylated steviol glycosides were identified by site-directed mutagenesis. Compared with CGTase-15, CGTase-15-Y199F mutant significantly increased the conversion rate of rebaudioside A (RA) to glucosylated steviol glycosides. Compared with CGTase-15, the content of short-chain glycosylated steviol glycosides catalyzed by CGTase-15-G265A mutant was significantly increased. Moreover, the function of Y199 and G265 was verified in other CGTases. The above mutation pattern has also been applied to CGTase-13 (a CGTase discovered by our laboratory with great potential in the production of glycosylated steviol glycosides), confirming that the catalytic product of CGTase-13-Y189F/G255A mutant has a better taste than that of CGTase-13.

Conclusions

This is the first report on the improvement of the sensory profiles of glycosylated steviol glycosides through site-directed mutagenesis of CGTase, which is significant for the production of glycosylated steviol glycosides.
Inhibiting HIF-1 signaling alleviates HTRA1-induced RPE senescence in retinal degeneration
Authors: Xu Wenchang , Liu Xinqi , Han Wenjuan , Wu Keling , Zhao Minglei , Mei Tingfang , Shang Bizhi , Wu Jinwen , Luo Jingyi , Lai Yuhua , Yang Boyu , Zhuo Yehong , Lu Lin , Liu Yizhi , Tian Xiao-li , Zhao Ling
Published: June 2023

Background

Age-related macular degeneration (AMD), characterized by the degeneration of retinal pigment epithelium (RPE) and photoreceptors, is the leading cause of irreversible vision impairment among the elderly. RPE senescence is an important contributor to AMD and has become a potential target for AMD therapy. HTRA1 is one of the most significant susceptibility genes in AMD, however, the correlation between HTRA1 and RPE senescence hasn’t been investigated in the pathogenesis of AMD.

Methods

Western blotting and immunohistochemistry were used to detect HTRA1 expression in WT and transgenic mice overexpressing human HTRA1 (hHTRA1-Tg mice). RT-qPCR was used to detect the SASP in hHTRA1-Tg mice and ARPE-19 cells infected with HTRA1. TEM, SA-β-gal was used to detect the mitochondria and senescence in RPE. Retinal degeneration of mice was investigated by fundus photography, FFA, SD-OCT and ERG. The RNA-Seq dataset of ARPE-19 cells treated with adv-HTRA1 versus adv-NC were analyzed. Mitochondrial respiration and glycolytic capacity in ARPE-19 cells were measured using OCR and ECAR. Hypoxia of ARPE-19 cells was detected using EF5 Hypoxia Detection Kit. KC7F2 was used to reduce the HIF1α expression both in vitro and in vivo.

Results

In our study, we found that RPE senescence was facilitated in hHTRA1-Tg mice. And hHTRA1-Tg mice became more susceptible to NaIO3 in the development of oxidative stress-induced retinal degeneration. Similarly, overexpression of HTRA1 in ARPE-19 cells accelerated cellular senescence. Our RNA-seq revealed an overlap between HTRA1-induced differentially expressed genes associated with aging and those involved in mitochondrial function and hypoxia response in ARPE-19 cells. HTRA1 overexpression in ARPE-19 cells impaired mitochondrial function and augmented glycolytic capacity. Importantly, upregulation of HTRA1 remarkably activated HIF-1 signaling, shown as promoting HIF1α expression which mainly located in the nucleus. HIF1α translation inhibitor KC7F2 significantly prevented HTRA1-induced cellular senescence in ARPE-19 cells, as well as improved the visual function in hHTRA1-Tg mice treated with NaIO3.

Conclusions

Our study showed elevated HTRA1 contributes to the pathogenesis of AMD by promoting cellular senescence in RPE through damaging mitochondrial function and activating HIF-1 signaling. It also pointed out that inhibition of HIF-1 signaling might serve as a potential therapeutic strategy for AMD.
Lactobacillus acidophilus and propionate attenuate Sjögren’s syndrome by modulating the STIM1-STING signaling pathway
Authors: Woo Jin Seok , Hwang Sun-Hee , Yang SeungCheon , Lee Kun Hee , Lee Yeon Su , Choi Jeong Won , Park Jin-Sil , Jhun JooYeon , Park Sung-Hwan , Cho Mi-La
Published: June 2023

Background

Sjögren’s syndrome (SS) is an autoimmune disease characterized by inflammation of the exocrine gland. An imbalance of gut microbiota has been linked to SS. However, the molecular mechanism is unclear. We investigated the effects of Lactobacillus acidophilus (L. acidophilus) and propionate on the development and progression of SS in mouse model.

Methods

We compared the gut microbiomes of young and old mice. We administered L. acidophilus and propionate up to 24 weeks. The saliva flow rate and the histopathology of the salivary glands were investigated, and the effects of propionate on the STIM1-STING signaling pathway were evaluated in vitro.

Results

Lactobacillaceae and Lactobacillus were decreased in aged mice. SS symptoms were ameliorated by L. acidophilus. The abundance of propionate-producing bacterial was increased by L. acidophilus. Propionate ameliorated the development and progression of SS by inhibiting the STIM1-STING signaling pathway.

Conclusions

The findings suggest that Lactobacillus acidophilus and propionate have therapeutic potential for SS.
Osteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to IL-1b or TNF
Authors: Defois Anais , Bon Nina , Charpentier Alexandre , Georget Melina , Gaigeard Nicolas , Blanchard Frederic , Hamel Antoine , Waast Denis , Armengaud Jean , Renoult Ophelie , Pecqueur Claire , Maugars Yves , Boutet Marie-Astrid , Guicheux Jerome , Vinatier Claire
Published: June 2023

Background

Osteoarthritis is an age-related disease that currently faces a lack of symptomatic treatment. Inflammation, which is mainly sustained by pro-inflammatory cytokines such as IL-1b, TNF, and IL-6, plays an important role in osteoarthritis progression. In this context, pro-inflammatory cytokines are widely used to mimic the inflammatory component of osteoarthritis in vitro. However, the therapeutic failures of clinical trials evaluating anti-cytokines drugs highlight the lack of overall understanding of the effects of these cytokines on chondrocytes.

Methods

Here, we generated a comprehensive transcriptomic and proteomic dataset of osteoarthritic chondrocytes treated with these cytokines to describe their pro-inflammatory signature and compare it to the transcriptome of non-osteoarthritic chondrocytes. Then, the dysregulations highlighted at the molecular level were functionally confirmed by real-time cellular metabolic assays.

Results

We identified dysregulation of metabolic-related genes in osteoarthritic chondrocytes but not in non-osteoarthritic chondrocytes. A metabolic shift, toward increased glycolysis at the expense of mitochondrial respiration, was specifically confirmed in osteoarthritic chondrocytes treated with IL-1b or TNF.

Conclusion

These data show a strong and specific association between inflammation and metabolism in osteoarthritic chondrocytes, which was not found in non-osteoarthritic chondrocytes. This indicates that the link between inflammation and metabolic dysregulation may be exacerbated during chondrocyte damage in osteoarthritis.
The tumor promoter cysteinyl leukotriene receptor 1 regulates PD-L1 expression in colon cancer cells via the Wnt/β-catenin signaling axis
Authors: Satapathy Shakti Ranjan , Ghatak Souvik , Sjölander Anita
Published: June 2023

Immunotherapy targeting programmed death-ligand 1 (PD-L1) or PD-1 in solid tumors has been shown to be clinically beneficial. However, in colorectal cancer (CRC), only a subset of patients benefit from PD-1/PD-L1 treatment. Previously, we showed that high cysteinyl leukotriene receptor 1 (CysLT1R) levels are associated with poor prognosis in CRC patients. Recently, we have revealed the role of the tumor promoter CysLT1R in drug resistance and stemness in colon cancer (CC) cells. Here, we show the role of the CysLT1R/Wnt/β-catenin signaling axis in the regulation of PD-L1 using both in vitro and in vivo preclinical model systems. Interestingly, we found that both endogenous and IFNγ-induced PD-L1 expression in CC cells is mediated through upregulation of CysLT1R, which enhances Wnt/β-catenin signaling. Therapeutic targeting of CysLT1R with its antagonist montelukast (Mo), as well as CRISPR/Cas9-mediated or doxycycline-inducible functional absence of CysLT1R, negatively regulated PD-L1 expression in CC cells. Interestingly, an anti-PD-L1 neutralizing antibody exhibited stronger effects together with the CysLT1R antagonist in cells (Apcmut or CTNNB1mut) with either endogenous or IFNγ-induced PD-L1 expression. Additionally, mice treated with Mo showed depletion of PD-L1 mRNA and protein. Moreover, in CC cells with combined treatment of a Wnt inhibitor and an anti-PD-L1 antibody was effective only in β-catenin-dependent (APCmut) context. Finally, analysis of public dataset showed positive correlations between the PD-L1 and CysLT1R mRNA levels. These results elucidate a previously underappreciated CysLT1R/Wnt/β-catenin signaling pathway in the context of PD-L1 inhibition in CC, which might be considered for improving the efficacy of anti-PD-L1 therapy in CC patients.
Breastfeeding environment and experiences at the workplace among health workers in the Upper East Region of Ghana
Authors: Kubuga Clement Kubreziga , Tindana Juliana
Published: June 2023

Background

Employed mothers have lower rates of breastfeeding, including health workers who are supposed to be advocates for breastfeeding. These working mothers need a supportive workplace environment to breastfeed, yet Ghana’s breastfeeding policy neither mentions the workplace breastfeeding environment nor offers any information on it.

Methods

A convergent parallel mixed-methods design was used in this study to determine: facilities with a complete breastfeeding support environment (BFSE); breastfeeding challenges experienced; coping strategies and motivators for breastfeeding among health workers in the Upper East Region of Ghana; and Management’s awareness of the need for an institutional breastfeeding support policy. Quantitative and qualitative data were analyzed using descriptive statistics and thematic analysis respectively. The research was conducted from January to April 2020.

Results

All facilities (39) had incomplete BFSE and management representatives of health facilities (39) did not have and were not aware that their respective facilities needed to have a specific workplace breastfeeding policy that fed into the national policy agenda. Breastfeeding challenges at workplaces included: lack of private space for breastfeeding; inadequate support from co-workers and management; emotional stress; and inadequate breastfeeding breaks and work options. Women adapted to these challenges by employing coping strategies such as: bringing children to work with / without caretakers; leaving children at home; seeking support from co-workers and family members; feeding children with supplementary foods; adding annual leave to maternity leave; breastfeeding in cars / offices; and sending children to daycare. Interestingly, the women were still motivated to breastfeed. Health benefits of breastmilk, the convenience and readily available nature of breastmilk, moral obligation to breastfeed, and cheap cost of breastmilk emerged as key motivators to breastfeed.

Conclusion

Our findings suggest that health workers have poor BFSE and are faced with numerous breastfeeding challenges. There is a need for programs that improve BFSE in health facilities.
Establishment and validation of a prognostic risk classification for patients with stage T1-3N0M0 esophageal squamous cell carcinoma
Authors: Huang Yang-Yu , Zheng Yan , Liang Shen-Hua , Wu Lei-Lei , Liu Xuan , Xing Wen-Qun , Ma Guo-Wei
Published: June 2023

Introduction

At present, clinical factors and hematological indicators have been proved to have great potential in predicting the prognosis of cancer patients, and no one has combined these two valuable indicators to establish a prognostic model for esophageal squamous cell carcinoma (ESCC) patients with stage T1-3N0M0 after R0 resection. To verify, we aimed to combine these potential indicators to establish a prognostic model.

Methods

Stage T1-3N0M0 ESCC patients from two cancer centers (including training cohort: N = 819, and an external validation cohort: N = 177)—who had undergone esophagectomy in 1995–2015 were included. We integrated significant risk factors for death events by multivariable logistic regression methods and applied them to the training cohort to build Esorisk. The parsimonious aggregate Esorisk score was calculated for each patient; the training set was divided into three prognostic risk classes according to the 33rd and 66th percentiles of the Esorisk score. The association of Esorisk with cancer-specific survival (CSS) was assessed using Cox regression analyses.

Results

The Esorisk model was: [10 + 0.023 × age + 0.517 × drinking history − 0.012 × hemoglobin–0.042 × albumin − 0.032 × lymph nodes]. Patients were grouped into three classes—Class A (5.14–7.26, low risk), Class B (7.27–7.70, middle risk), and Class C (7.71–9.29, high risk). In the training group, five-year CSS decreased across the categories (A: 63%; B: 52%; C: 30%, Log-rank P < 0.001). Similar findings were observed in the validation group. Additionally, Cox regression analysis showed that Esorisk aggregate score remained significantly associated with CSS in the training cohort and validation cohort after adjusting for other confounders.

Conclusions

We combined the data of two large clinical centers, and comprehensively considered their valuable clinical factors and hematological indicators, established and verified a new prognostic risk classification that can predict CSS of stage T1-3N0M0 ESCC patients.
The challenges of international collaboration in conflict and health research: experience from the Research for Health in Conflict-Middle East and North Africa (R4HC-MENA) partnership
Authors: Lin Chiu-Yi , Meagher Kristen , Bricknell Martin , Patel Preeti , El Achi Nassim , Kutluk Tezer , Harding Richard , Kienzler Hanna , Giacaman Rita , Mukherji Deborah , Shamieh Omar , Sullivan Richard
Published: June 2023

Background

Healthcare is a basic human right extending across all humanitarian contexts, including conflict. Globally, two billion people are living under conditions of insecurity and violent armed conflict with a consequent impact on public health. Health research in conflict-affected regions has been recognised as important to gain more understanding of the actual needs of such populations, to optimise healthcare delivery, as well as to inform advocacy and policy change. International collaborative research maximises the resources and skills available for dealing with global health issues, builds capacity and endeavours to ensure the research reflects real needs of the populations. Under the UK’s Global Challenge Research Fund in 2017 a number of such international programs were created including the Research for Health in Conflict-Middle East and North Africa (R4HC-MENA) partnership to build capacity in conflict and health research as well as study specific areas, namely noncommunicable diseases in conflict (cancer & mental health) and the political economy of health in conflict.

Methods

A qualitative study using semi-structured online interviews was conducted to explore researchers’ and stakeholders’ perspectives on the R4HC-MENA programme over its lifetime from 2017 to 2021. It aimed to understand the factors that influenced and accelerated international collaboration within the R4HC-MENA programme on conflict and health research, and to provide deeper insights into the implementation of the programme. Data collection was conducted from March 2022 to June 2022. Purposive and snowball sampling techniques were used for participant recruitment. Thematic analysis was applied for data analysis.

Results

Twelve researchers/stakeholders participated in this study: four men and eight women. Four main themes were generated: Theme 1: Network building (personal and institutional levels); Theme 2: Hierarchies and power dynamics (power imbalance between different academic status, genders and institutions); Theme 3: Communication challenges; Theme 4: Career development (management, leadership, research, and teaching skills).

Conclusions

This study provided preliminary insights into perspectives on international collaboration in a major international programme of research on conflict and health. Several key challenges and outputs were generated by the researchers in this study. The findings are important for further developing effective strategies to tackle the challenge of power imbalance and ineffective communication in international research collaborations.
How do Italian pediatric endocrinologists approach gender incongruence?
Authors: Ciancia Silvia , Iughetti Lorenzo
Published: June 2023

Background

Gender incongruence (GI) is a term used to describe a marked and persistent incompatibility between the sex assigned at birth (SAAB) and the experienced gender. Some persons presenting with GI experience a severe psychological distress defined as gender dysphoria (GD).. Although the prevalence of GI is probably underestimated, recently a great increase in numbers of transgender and gender diverse (TGD) youths presenting at the gender clinics has been registered. After a careful multidisciplinary evaluation and upon acquisition of informed consent from the youth and the legal guardian(s), puberty suppression can be started in TGD youths, followed by the addition of gender affirming hormones (GAH) by the age of 16 years. Although Italian specific guidelines are available, their application is often complex because of (among other reasons) lack of specialized centers and healthcare professional with experience in the field and the regional differences within the Italian healthcare system.

Main body

To investigate the care offered to TGD youths across Italy, we proposed a survey of 20 questions to the directors of the 32 Italian Centers of pediatric endocrinology participating to the Study Group on Growth and Puberty of the Italian Society of Pediatric Endocrinology (ISPED). Eighteen pediatric endocrinologists representative of 16 different centers belonging to 11 different regions responded to the survey. In the large majority of centers TGD youths are taken in charge between the age of 12 and 18 years and at least three healthcare professional are involved. Most of Italian pediatric endocrinologists follow only a very limited number of TGD youths and reference centers for TGD youths are lacking.

Conclusion

There is an urgent need for gender clinics (homogeneously distributed on the national territory) where TGD youths can access high standard care.
Spatial distribution pattern across multiple microbial groups along an environmental stress gradient in tobacco soil
Authors: Li Pengfei , Xu Tianyang , Hu Qiulong , Gu Songsong , Yang Yishuai , Wang Zhengqiang , Deng Xiangdong , Wang Bin , Li Wei , Zhu Yanmei
Published: June 2023

Background

It has become commonplace to explore the spatial distribution patterns of microbial communities in natural ecosystems. However, few have looked at the responses of community diversity, structure, and assembly processes from different microbial groups to changes in environmental stress caused by altitude.

Purpose

We investigated the spatial and biogeographical patterns of different microbial groups, including bacteria, fungi, and protists, from tobacco soil along an altitudinal gradient to evaluate the influence of geographic distance and environmental stress on microbial distribution pattern.

Methods

DDR (distance decay relationship) model was calculated to evaluate the spatial distribution pattern. Then, NCM (neutral community model) and two null-modelling-based approaches, NST (normalized stochasticity ratio) and iCAMP (the infer community assembly mechanism by phylogenetic-bin-based null model analysis), were used to reveal the importance of stochastic and deterministic processes to microbial community assembly by utilizing high-throughput sequencing data.

Result

Bacterial community α-diversity decreased significantly (P < 0.05) with increasing environmental stress. Moreover, all communities exhibited a significant DDR pattern (P < 0.001), with the slope of bacteria (0.146) being significantly higher (P < 0.05) than that of fungi (0.059) and protists (0.060). The results of NCM and the two null-modelling-based approaches revealed the importance of stochastic processes to bacterial (83.4%) and protist (69.9%) communities, which were primarily shaped by drift and dispersal limitation, respectively; meanwhile, deterministic processes were important to the fungal community (53.7%). Additionally, we found a significant correlation between the assembly process and geographic distance (P < 0.05).

Conclusion

Our study provides a complementary perspective to the study of multiple hierarchical groups across different spatial scales (i.e., horizontal and vertical scales).

Graphical Abstract
Stereotactic ablative body radiation therapy for isolated pulmonary metastases from pancreatic cancer after metastectomy with positive margins: a case report
Authors: Alnsour Anoud , Le Hien , Byrne Adam , Rodgers Nick , Roos Daniel
Published: June 2023

Background

Isolated pulmonary oligometastases as the first site of dissemination after initial resection of pancreatic ductal adenocarcinoma (PC) is a rare event, and the treatment in this subgroup is challenging. Recurrence in the lung after initial primary tumour resection is associated with the most long-term survivors of patients with metastatic PC. Stereotactic ablative body radiation therapy (SABR) or metastectomy for pulmonary oligometastases from PC is becoming more common. However, patients with close or positive margins after metastectomy for isolated pulmonary metastatic PC are at high risk for recurrence. This requires a treatment capable of achieving high rates of local control and improved quality of life by delaying the need for systemic chemotherapy. In other settings, SABR has been shown to achieve these goals, allowing safe dose escalation with excellent conformity and short duration of treatment.

Case presentation

We report the case of a 48-year old Caucasian man with a history of locally advanced PC initially treated with neoadjuvant chemotherapy followed by Whipple’s resection in August 2016. After a disease-free interval of 3 years, he developed three isolated pulmonary metastases which were treated with local resection. In the setting of microscopically positive resection margins (R1), adjuvant lung SABR was delivered to all three sites. His treated lung disease remained radiologically stable for up to twenty months after SABR. Treatment was well tolerated. In January 2021, he developed a malignant pre-tracheal node which was treated with conventionally fractionated radiotherapy and remained controlled for the duration of follow-up. A year later, he developed widespread metastatic disease including pleura, bone and adrenal gland, together with presumed progression in one of the original lung lesions, receiving palliative radiotherapy for right chest wall pain. He was later found to have an intracranial metastasis and died in February 2022, 5½ years after initial treatment.

Conclusion

We present the case of a patient treated with SABR after R1 resection of 3 isolated pulmonary metastases from PC, with no treatment toxicities and durable local control. For well-selected patients in this setting, adjuvant lung SABR may be a safe and effective treatment option.