bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on the relationship between common metabolic syndrome and meteorological factors in Wuhu, a subtropical humid city of China
Authors: Zhang Tao , Ni Man , Jia Juan , Deng Yujie , Sun Xiaoya , Wang Xinqi , Chen Yuting , Fang Lanlan , Zhao Hui , Xu Shanshan , Ma Yubo , Zhu Jiansheng , Pan Faming
Published: November 2023

As climate conditions deteriorate, human health faces a broader range of threats. This study aimed to determine the risk of death from metabolic syndrome (MetS) due to meteorological factors. We collected daily data from 2014 to 2020 in Wuhu City, including meteorological factors, environmental pollutants and death data of common MetS (hypertension, hyperlipidemia and diabetes), as well as a total number of 15,272 MetS deaths. To examine the relationship between meteorological factors, air pollutants, and MetS mortality, we used a generalized additive model (GAM) combined with a distributed delay nonlinear model (DLNM) for time series analysis. The relationship between the above factors and death outcomes was preliminarily evaluated using Spearman analysis and structural equation modeling (SEM). As per out discovery, diurnal temperature range (DTR) and daily mean temperature (T mean) increased the MetS mortality risk notably. The ultra low DTR raised the MetS mortality risk upon the general people, with the highest RR value of 1.033 (95% CI: 1.002, 1.065) at lag day 14. In addition, T mean was also significantly associated with MetS death. The highest risk of ultra low and ultra high T mean occured on the same day (lag 14), RR values were 1.043 (95% CI: 1.010, 1.077) and 1.032 (95% CI: 1.003, 1.061) respectively. Stratified analysis’s result showed lower DTR had a more pronounced effect on women and the elderly, and ultra low and high T mean was a risk factor for MetS mortality in women and men. The elderly need to take extra note of temperature changes, and different levels of T mean will increase the risk of death. In warm seasons, ultra high RH and T mean can increase the mortality rate of MetS patients.
The relationship between social support and academic engagement among university students: the chain mediating effects of life satisfaction and academic motivation
Authors: Chen Chunmei , Bian Fei , Zhu Yujie
Published: November 2023

Background

University students’ academic engagement has a significant impact on their academic performance and career development.

Methods

In order to explore the influential mechanisms of social support on university students’ academic engagement and the mediating role of academic motivation and life satisfaction, this study used the Adolescent Social Support Scale, University Students’ Academic Engagement Scale Questionnaire, Adolescent Student Life Satisfaction Scale and University Students’ Academic Motivation Questionnaire, to conduct a questionnaire survey and empirical analysis on 2106 Chinese university students.

Results

(1) social support significantly and positively predicts academic engagement; (2) social support influences academic engagement through the mediating effect of life satisfaction; (3) social support influences academic engagement through the mediating effect of academic motivation; (4) life satisfaction and academic motivation play a chain mediating role in the effect of social support on academic engagement.

Conclusions

This study contributes to understanding the underlying mechanisms of the relationship between social support and academic engagement, which in turn provides insights for universities and the departments concerned to make measures to improve the level of university students’ academic engagement.
Parental separation, negative life events and mental health problems in adolescence
Authors: Karhina Kateryna , Bøe Tormod , Hysing Mari , Nilsen Sondre Aasen
Published: November 2023

Background

Parental separation is associated with mental health problems in adolescence. One suggested pathway for this association is through the accumulated exposure to stress and other negative life events. This study aimed to document the distribution of negative life events among adolescents with separated compared to non-separated parents, and to assess the direct and interactive associations between parental separation, negative life events, and mental health problems in adolescence.

Methods

Data stem from the cross-sectional population-based youth@hordaland study of adolescents (aged 16–19) conducted in Norway in 2012, providing self-reported information about parental separation, negative life events, and depression-, anxiety-, conduct-, and ADHD symptoms. Regression analyses were used to assess the direct and interactive associations between parental separation, negative life events, and mental health problems.

Results

Adolescents with separated parents had more mental health problems across all symptom scales compared to peers with non-separated parents, with standardized mean differences [SMDs] ranging from 0.15 to 0.20. Negative life events moderately attenuated these differences (reduced the SMDs with about 0.04–0.08, depending on the outcome). However, none of the interactions between parental separation and negative life events on mental health problems were statistically significant.

Conclusions

Higher exposure to negative life events explains parts of the association between parental separation and mental health problems in adolescence. However, a parental separation does not seem to increase the vulnerability of the effects of negative life events on adolescents’ mental health. Assessing exposure to negative life events is important when providing mental health services to adolescents, particularly to those who have parents separated.
Sex differences in comorbidities and mortality risk among patients with chronic obstructive pulmonary disease: a study based on NHANES data
Authors: Li Na , Li Xiaoli , Liu Minjie , Wang Yakang , Wang Junning
Published: November 2023

Background

Patients with chronic obstructive pulmonary disease (COPD) commonly have coexisting comorbidities that contribute to higher exacerbation frequency, poorer health status, and increased all-cause mortality; however, there are only a few studies available on the sex discrepancy in the comorbidity distribution and outcomes among COPD patients, and there is limited information about the discrepancy in all-cause mortality between men and women.

Methods

Based on data from the U.S. National Health and Nutrition Examination Survey conducted between 2007 and 2012, we compared participants aged 40–79 years with spirometry-defined COPD to compare the prevalence of comorbidities between men and women. The survival of the subjects was documented, and the sex discrepancy was determined using Kaplan–Meier analysis. Comorbidities and all-cause mortality were analyzed by using a Cox proportional hazards model to determine their strength of association in different sex groups.

Results

Compared to men, women had a significantly higher prevalence of asthma (OR 1.93, 95% CI 1.46 to 2.57, p < 0.001) and arthritis (OR 1.77, 95% CI 1.39 to 2.24, p < 0.001). Women had a significantly lower prevalence of coronary heart disease (OR 0.48, 95% CI 0.27 to 0.87, p = 0.015) and gout (OR 0.42, 95% CI 0.25 to 0.67, p = 0.001). Kaplan–Meier analysis revealed that compared with that of the female group, the survival rate of the male group was significantly lower (p < 0.001). Among men, the presence of anemia (HR 2.38, [95% CI 1.52–3.73], p < 0.001), gout (HR 1.55, [95% CI 1.04–2.30], p = 0.029) and congestive heart failure comorbidities (HR 1.85, [95% CI 1.12–3.04] p = 0.016) was associated with a higher risk of mortality; among women, the presence of anemia (HR 2.21, [95% CI 1.17–4.20], p = 0.015) and stroke (HR 2.04, [95% CI 1.07–3.88], p = 0.031) comorbidities was associated with a higher risk of mortality after adjusting for age, race/Hispanic status, BMI, smoking status, FEV1% predicted and prevalent comorbidities.

Conclusions

COPD-related comorbidities and all-cause mortality were discrepant between men and women, and men had poorer survival than women in the nationally representative data that were analyzed.
Thyroid function and opium use disorder: a cross-sectional study on the Fasa adults cohort study (FACS), 2017
Authors: Pezeshki Babak , Pourmontaseri Hossein , Homayounfar Reza , Moghaddam Maryam Talebi , Dehghan Azizallah
Published: November 2023

Background

Addiction increases the risk of different lifelong disorders. However, there are limited studies evaluating the effects of opioid use disorder (OUD) on thyroid function. The present study aimed to compare the thyroid function of individuals with and without OUD.

Methods

This cross-sectional study was conducted on 700 eligible participants of the Persian Cohort of Fasa, Iran. Pregnant women and participants with false or missing data were excluded from the study. Remained participants were divided into case and control groups based on the recorded history of OUD. Frozen plasma samples of the cohort bank were used to determine the levels of T3, T4, and thyroid-stimulating hormone (TSH). The thyroid function was compared between the two groups using the Mann-Whitney test (P < 0.05).

Results

The mean age of the final studied population (n = 648) was 54.0 ± 9.8 years, including 336 men (49.1%) and 197 participants with OUD (28.8%). The median levels of TSH, T4, and T3 were 2.91 ± 4.61, 9.26 ± 3.65, and 1.22 ± 0.49, respectively. The case group had significantly higher TSH (3.72 ± 6.2 vs. 2.58 ± 3.75, P < 0.001) and lower T4 (8 ± 3.6 vs. 9.8 ± 3.5, P < 0.001). Also, T3 was slightly lower in the case group (1.1 ± 0.5 vs. 1.3 ± 0.5; P = 0.369), although this association was only significant in female opium users (P < 0.001).

Conclusions

The present findings revealed that OUD caused a reduction in T4 while increasing TSH. Therefore, OUD may lead to the development of primary hypothyroidism, which needs to be investigated in future studies.
Prevalence and correlates of multimorbidity among patients attending AYUSH primary care settings in Delhi-National Capital Region, India
Authors: Varanasi Roja , Sinha Abhinav , Nayak Debadatta , Manchanda Raj K. , Janardhanan Rajiv , Tandon Simran , Pati Sanghamitra
Published: November 2023

Introduction

India has a multifaceted healthcare system and recognizes complementary and alternative systems of medicine (AYUSH) that cater to the healthcare needs of people. Multimorbidity requires frequent visits to physicians and long-term use of medications, due to which people tend to prefer AYUSH systems as they provide holistic patient-centered treatment. Hence, we aimed to estimate the prevalence of multimorbidity and assess its correlates among patients attending AYUSH primary care clinics in Delhi.

Methods

A cross-sectional study was conducted among 943 patients aged ≥ 18 years attending various AYUSH primary care clinics in Delhi from September 2021 to February 2022, employing a stratified random sampling technique. Descriptive statistics such as frequency and proportion were used to report the prevalence of multimorbidity (two or more chronic conditions in an individual out of the 33 conditions listed as per the Multimorbidity Assessment Questionnaire for Primary Care). A multivariable logistic regression assessed the association between various socio-demographic characteristics and multimorbidity, presented as an adjusted odds ratio (AOR) with a 95% confidence interval (CI).

Results

The prevalence of diabetes (14.7%) was found to be the highest (out of all included chronic conditions) among the patients attending various AYUSH primary care settings. The overall prevalence of multimorbidity was observed to be around 39.4%. We observed a higher likelihood of having multimorbidity among participants aged ≥ 70 years [AOR: 9.19 (95% CI: 3.75–22.54)], females [AOR: 1.57 (95% CI: 1.04–2.37)], and middle class [AOR: 2.23 (95% CI: 1.45–3.43)].

Conclusion

Multimorbidity was evidently prevalent across AYUSH primary care settings, which cannot be overlooked. The results suggest behavioral change communication may be aimed at older individuals, females, and the middle class.
Evaluation of causal associations between interleukin-18 levels and immune-mediated inflammatory diseases: a Mendelian randomization study
Authors: Wu Jialing , Zhang Xi , Wu Dongze , Jin Ou , Gu Jieruo
Published: November 2023

Background

Altered interleukin (IL)-18 levels are associated with immune-mediated inflammatory diseases (IMIDs), but no studies have investigated their causal relationship. This study aimed to examine the causal associations between IL-18 and IMIDs.

Methods

We performed a two-sample Mendelian randomization (MR) analysis. Genetic variants were selected from genome-wide association study datasets following stringent assessments. We then used these variants as instrumental variables to estimate the causal effects of IL-18 levels on the risk of developing five common IMIDs: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), ankylosing spondylitis (AS), and psoriasis. We used the inverse variance-weighted (IVW) method as the primary analysis, with sensitivity analyses performed to avoid potential bias. Reverse-direction MR analyses were performed to rule out the possibility of reverse associations.

Results

We found that genetically determined higher circulating IL-18 levels were causally associated with a higher risk for SLE (PIVW = 0.009; OR, 1.214; 95% CI, 1.049 − 1.404) and IBD (PIVW < 0.001; OR, 1.142; 95% CI, 1.062 − 1.228), but found no significant associations of IL-18 with RA (PIVW = 0.496; OR, 1.044; 95% CI, 0.923 − 1.180), AS (PIVW = 0.021; OR, 1.181; 95% CI, 1.025 − 1.361), or psoriasis (PIVW = 0.232; OR, 1.198; 95% CI, 0.891 − 1.611). In the reverse direction, no causal relationship existed between SLE or IBD and IL-18 levels. Globally, sensitivity studies using alternative MR methods supported the results that were robust and reliable. The Cochran’s Q test, MR-Egger intercept, and MR-Pleiotropy RESidual Sum and Outlier excluded the influence of heterogeneity, horizontal pleiotropy, and outliers.

Conclusions

We have demonstrated that elevated IL-18 levels increase the risk of SLE and IBD but not RA, AS, or psoriasis. The results enhanced our understanding of IL-18 in the pathology of IMIDs.
Improved production of Taxol® precursors in S. cerevisiae using combinatorial in silico design and metabolic engineering
Authors: Malcı Koray , Santibáñez Rodrigo , Jonguitud-Borrego Nestor , Santoyo-Garcia Jorge H. , Kerkhoven Eduard J. , Rios-Solis Leonardo
Published: November 2023

Background

Integrated metabolic engineering approaches that combine system and synthetic biology tools enable the efficient design of microbial cell factories for synthesizing high-value products. In this study, we utilized in silico design algorithms on the yeast genome-scale model to predict genomic modifications that could enhance the production of early-step Taxol® in engineered Saccharomyces cerevisiae cells.

Results

Using constraint-based reconstruction and analysis (COBRA) methods, we narrowed down the solution set of genomic modification candidates. We screened 17 genomic modifications, including nine gene deletions and eight gene overexpressions, through wet-lab studies to determine their impact on taxadiene production, the first metabolite in the Taxol® biosynthetic pathway. Under different cultivation conditions, most single genomic modifications resulted in increased taxadiene production. The strain named KM32, which contained four overexpressed genes (ILV2, TRR1, ADE13, and ECM31) involved in branched-chain amino acid biosynthesis, the thioredoxin system, de novo purine synthesis, and the pantothenate pathway, respectively, exhibited the best performance. KM32 achieved a 50% increase in taxadiene production, reaching 215 mg/L. Furthermore, KM32 produced the highest reported yields of taxa-4(20),11-dien-5α-ol (T5α-ol) at 43.65 mg/L and taxa-4(20),11-dien-5-α-yl acetate (T5αAc) at 26.2 mg/L among early-step Taxol® metabolites in S. cerevisiae.

Conclusions

This study highlights the effectiveness of computational and integrated approaches in identifying promising genomic modifications that can enhance the performance of yeast cell factories. By employing in silico design algorithms and wet-lab screening, we successfully improved taxadiene production in engineered S. cerevisiae strains. The best-performing strain, KM32, achieved substantial increases in taxadiene as well as production of T5α-ol and T5αAc. These findings emphasize the importance of using systematic and integrated strategies to develop efficient yeast cell factories, providing potential implications for the industrial production of high-value isoprenoids like Taxol®.
Evaluating the efficacy and timing of blood purification modalities in early-stage hyperlipidemic acute pancreatitis treatment
Authors: Wang Jianjun , Xia Yang , Cao Yuan , Cai Xianfu , Jiang Shichun , Liao Yougang , Shi Mingsong , Luo Huiwen , Wang Decai
Published: November 2023

Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is characterized by a violent cytokine storm-driven inflammation and is associated with a predisposition to severe disease. The treatment strategy for HTG-AP consists mainly of conventional symptomatic and lipid-lowering treatments. For early-stage HTG-AP, blood purification (BP) can rapidly and effectively reduce serum triglyceride and inflammatory cytokine levels, block the development of systemic inflammatory response syndrome, and improve patient outcomes. Currently, the primary modalities for BP in patients with HTG-AP include plasma exchange, hemoperfusion, and hemofiltration. When using BP to treat patients with HTG-AP, a comprehensive analysis incorporating the elevated lipid levels and severity of the patient’s condition contributes to the selection of different treatment modes. Moreover, the timing of the treatment is also imperative. Early intervention is associated with a better prognosis for patients with HTG-AP requiring lipid-lowering treatment.
Development and validation of the systemic lupus erythematous scale amongst the system of quality of life instruments for chronic diseases QLICD-SLE (V2.0)
Authors: Liu Yuxi , Zhang Jiaqi , Xue Honghong , Chen Mingyang , Xie Tong , Wan Chonghua
Published: November 2023

Objective

The present study is aimed to develop and validate a quality of life scale for systemic lupus erythematosus (SLE) patients with Chinese cultural background, QLICD-SLE (V2.0).

Methods

The QLICD-SLE (V2.0) was developed using a systematic approach that involved focus groups, nominal discussions, and pilot testing. A total of 428 SLE patients participated in the scale's assessment. Validity was examined through qualitative analysis, item domain correlation, multidimensional scaling, and factor analysis. Reliability was assessed using Pearson's correlation and Cronbach's alpha coefficients. To evaluate responsiveness, paired T-tests were conducted to compare pre- and post-treatment measurements with the standardised response mean (SRM) being calculated.

Results

Correlation and factor analyses demonstrated strong construct validity. When using SF-36 as criteria, the correlation between various domains of QLICD-SLE and SF-36 ranged from 0.55 to 0.70. Test–retest correlation coefficients exceeded 0.71, and Cronbach’s alpha coefficients for both measurements in each domain were greater than or equal to 0.75. T-test results showed that both the overall score and most facet scores within each domain showed statistically significant changes after treatment (P < 0.05), indicating reasonable responsiveness.

Conclusion

The QLICD-SLE (V2.0) appears to be a valid and reliable instrument for assessing the quality of life in patients with SLE.
Government, governance, and place-based approaches: lessons from and for public policy
Authors: Klepac Bojana , Mowle Amy , Riley Therese , Craike Melinda
Published: November 2023

Background

Place-based approaches are increasingly applied to address the determinants of health, many of which are complex problems, to ultimately improve population health outcomes. Through public policy, government actions can affect the effectiveness of place-based approaches by influencing the conceptualisation, development, implementation, governance, and/or evaluation of place-based approaches. Despite the important role of public policy, there has been limited examination of public policy related to place-based approaches. We add to the limited knowledge base by analysing Australian national public policy, to explore: (1) the definitions, conceptualisations, and characteristics of place-based approaches in public policy; (2) the government’s perception and communication of its role in place-based approaches; and (3) the extent to which government policy reflects the necessary conditions for successful place-based governance developed by Marsh and colleagues, namely localised context, embedded learning, and reciprocal accountability.

Methods

This research was underpinned by the Theory of Systems Change and methodologically informed by the READ approach to document analysis. Ritchie and Spencer’s framework method was utilised to analyse the data.

Results

We identified and reviewed 67 policy documents. In terms of conceptualisation, common characteristics of place-based approaches related to collaboration, including community in decision-making, responsiveness to community needs, and suitability of place-based approaches to address complex problems and socio-economic determinants of health. Three roles of government were identified: funder, partner, and creator of a supportive policy environment. From the three criteria for successful place-based governance,localisedcontextwas the most dominant across the documents andreciprocalaccountabilitythe least.

Conclusions

Based on our findings, we drew key implications for public policy and research. There was a disproportionate emphasis on the bottom-up approach across the documents, which presents the risk of diminishing government interest in place-based approaches, potentially burdening communities experiencing disadvantage beyond their capacities. Governments engaged in place-based approaches should work towards a more balanced hybrid approach to place-based approaches that maintain the central functions of government while allowing for successful place-based governance. This could be achieved by promoting consistency in conceptualisations of ‘place-based’, employing an active role in trust building, advancing the creation of a supportive policy environment, and embedding ‘learning’ across place-based approaches.
Phylogenomic assessment of 23 equid alphaherpesvirus 1 isolates obtained from USA-based equids
Authors: Emelogu Ugochi , Lewin Andrew C. , Balasuriya Udeni B. R. , Liu Chin-Chi , Wilkes Rebecca P. , Zhang Jianqiang , Mills Erinn P. , Carter Renee T.
Published: November 2023

Background

Equid alphaherpesvirus 1 (EHV-1) is a global viral pathogen of domestic equids which causes reproductive, respiratory and neurological disease. Few isolates acquired from naturally infected USA-based hosts have been fully sequenced and analyzed to date. An ORF 30 (DNA polymerase) variant (A2254G) has previously been associated with neurological disease in host animals. The purpose of this study was to perform phylogenomic analysis of EHV-1 isolates acquired from USA-based hosts and compare these isolates to previously sequenced global isolates.

Methods

EHV-1 was isolated from 23 naturally infected USA-based equids (6 different states, 15 disease outbreaks) with reproductive (22/23) or neurological disease (1/23). Following virus isolation, EHV-1 DNA was extracted for sequencing using Illumina MiSeq. Following reference-based assembly, whole viral genomes were annotated and assessed. Previously sequenced EHV-1 isolates (n = 114) obtained from global host equids were included in phylogenomic analyses.

Results

The overall average genomic distance was 0.0828% (SE 0.004%) for the 23 newly sequenced USA isolates and 0.0705% (SE 0.003%) when all 137 isolates were included. Clade structure was predominantly based on geographic origin. Numerous nucleotide substitutions (mean [range], 179 [114–297] synonymous and 81 [38–120] non-synonymous substitutions per isolate) were identified throughout the genome of the newly sequenced USA isolates. The previously described ORF 30 A2254G substitution (associated with neurological disease) was found in only one isolate obtained from a host with non-neurological clinical signs (reproductive disease), six additional, unique, non-synonymous ORF 30 substitutions were detected in 22/23 USA isolates. Evidence of recombination was present in most (22/23) of the newly sequenced USA isolates.

Conclusions

Overall, the genomes of the 23 newly sequenced EHV-1 isolates obtained from USA-based hosts were broadly similar to global isolates. The previously described ORF 30 A2254G neurological substitution was infrequently detected in the newly sequenced USA isolates, most of which were obtained from host animals with reproductive disease. Recombination was likely to be partially responsible for genomic diversity in the newly sequenced USA isolates.
The effect of different posterior inclinations of tibial component on tibiofemoral contact pressures after unicompartmental knee arthroplasty
Authors: Yuan Bo , Mo Zhongjun , Zhang Kuan , Zhu Xu , Yan Songhua , Zeng Jizhou
Published: November 2023

Background

Different posterior inclinations of tibial component after unicompartmental knee arthroplasty (UKA) may lead to different biomechanical characteristics of the knee joint. This finite element study was designed to investigate the tibiofemoral contact pressures after UKA with different posterior inclinations of tibial component.

Methods

Finite element model of a healthy knee joint was constructed, and mobile-bearing (MB) UKA models with 5 different posterior inclinations (3°, 5°, 7°, 9° and 11°) of tibial components were simulated. The maximum contact pressures of tibial plateau cartilage in the lateral compartment and polyethylene insert in the medial compartment were calculated based on the ground reaction force and the angle of the knee flexion obtained by 3D motion capture system.

Results

The loading ratio of medial and lateral compartments during standing stance (medial 54.49%, lateral 45.51%) and tibial anterior displacement (134 N, 3.89 mm) of healthy knee was basically consistent with previous experimental data. The maximum contact pressures of the medial meniscus and lateral tibial plateau cartilage of the healthy knee during standing stance were 2.14 MPa and 1.57 MPa, respectively. At the static standing phase, the maximum contact pressures of the polyethylene insert decreased from 17.90 to 17.29 Mpa, and the maximum contact pressures of the tibial plateau cartilage in the lateral compartment increased from 0.81 to 0.92 Mpa following an increase in the posterior inclination of the tibial component. At the first peak of ground reaction force, the maximum contact pressures of polyethylene insert increased from 22.37 to 25.16 MPa, and the maximum contact pressures of tibial plateau cartilage in the lateral compartment increased from 3.03 to 3.33 MPa, with the increase in the posterior inclination of the tibial component. At the second peak of ground reaction force, the maximum contact pressures of polyethylene insert decreased from 2.34 to 2.22 MPa with the increase in posterior inclination of tibial component.

Conclusion

The preoperative and postoperative finite element models of MB UKA were well established. The results showed that the maximum contact pressures of the polyethylene insert did not change significantly with the increase in the posterior inclination of the tibial prosthesis, while the maximum contact pressures of the tibial plateau cartilage of the lateral compartment increased when the posterior inclination of the tibial prosthesis was > 7°. Our results also show that the maximum contact pressures were greater with an excessive inclination angle (11°) of the tibial component, and the pressures of the tibial plateau cartilage in the lateral compartment were more concentrated on the posterior area. This study, therefore, proposes that excessive osteotomy should be avoided.
Choices for cancer prevention for women with a BRCA1 mutation? a personal view
Authors: Narod Steven A.
Published: November 2023

With widespread testing for susceptibility genes, increasing numbers of women are being identified to carry a mutation in one of many genes which renders them susceptible to cancer. The first gene to be identified (in 1994) was BRCA1 which increases a woman’s risk for breast cancer (70%) and ovarian cancer (40%). The prevalence of BRCA1 gene mutations has been studied widely and in many countries, mostly in women affected with cancer. In many settings testing is offered routinely to women with serous ovarian cancer or early-onset or triple-negative breast cancer. It is preferable to identify a mutation in a healthy women prior to the diagnosis of cancer. The basic strategies for prevention include surgical prevention, chemoprevention and screening (early detection). Much progress has been made in the past two decades evaluating the benefits of these three approaches. In this commentary I provide my personal views regarding these various interventions in the context of counselling a newly diagnosed health woman with a BRCA1 mutation.
Combination of serum and peritoneal 1.3-beta-d-glucan can rule out intra-abdominal candidiasis in surgical critically ill patients: a multicenter prospective study
Authors: Novy Emmanuel , Rivière Jérémie , Nguyen Maxime , Arfeuille Gaëlle , Louis Guillaume , Bouhemad Bélaïd , Pottecher Julien , Hecketsweiler Stéphane , Germain Adeline , Laithier François-Xavier , Losser Marie-Reine , Debourgogne Anne , Bernard Yohann , Rousseau Hélène , Baumann Cédric , Luc Amandine , Birckener Julien , Machouart Marie-Claire , Guerci Philippe
Published: November 2023

Background

Intra-abdominal candidiasis (IAC) is difficult to predict in critically ill patients with intra-abdominal infection, leading to the overuse of antifungal treatments. Serum and peritoneal 1.3-beta-d-glucan (sBDG and pBDG) have been proposed to confirm or invalidate the diagnosis of IAC, but clinical studies have reported inconsistent results, notably because of heterogeneous populations with a low IAC prevalence. This study aimed to identify a high-risk IAC population and evaluate pBDG and sBDG in diagnosing IAC.

Methods

This prospective multicenter noninterventional French study included consecutive critically ill patients undergoing abdominal surgery for abdominal sepsis. The primary objective was to establish the IAC prevalence. The secondary objective was to explore whether sBDG and pBDG could be used to diagnose IAC. Wako® beta-glucan test (WT, Fujifilm Wako Chemicals Europe, Neuss, Germany) was used for pBDG measurements. WT and Fungitell® beta-d-glucan assay (FA, Associate of Cape Cod, East Falmouth, USA) were used for sBDG measurements.

Results

Between 1 January 2020 and 31 December 2022, 199 patients were included. Patients were predominantly male (63%), with a median age of 66 [54–72] years. The IAC prevalence was 44% (87/199). The main IAC type was secondary peritonitis. Septic shock occurred in 63% of cases. After multivariate analysis, a nosocomial origin was associated with more IAC cases (P = 0.0399). The median pBDG level was significantly elevated in IAC (448 [107.5–1578.0] pg/ml) compared to non-IAC patients (133 [16.0–831.0] pg/ml), P = 0.0021. For a pBDG threshold of 45 pg/ml, the negative predictive value in assessing IAC was 82.3%. The median sBDG level with WT (n = 42) at day 1 was higher in IAC (5 [3.0–9.0] pg/ml) than in non-IAC patients (3 [3.0–3.0] pg/ml), P = 0.012. Similarly, median sBDG level with FA (n = 140) at day 1 was higher in IAC (104 [38.0–211.0] pg/ml) than in non-IAC patients (50 [23.0–141.0] pg/ml), P = 0.009. Combining a peritonitis score < 3, sBDG < 3.3 pg/ml (WT) and pBDG < 45 pg/ml (WT) yielded a negative predictive value of 100%.

Conclusion

In critically ill patients with intra-abdominal infection requiring surgery, the IAC prevalence was 44%. Combining low sBDG and pBDG with a low peritonitis score effectively excluded IAC and could limit unnecessary antifungal agent exposure.

Trial registration: The study was registered with ClinicalTrials.gov (ID number 03997929, first registered on June 24, 2019).

Graphical abstract
Long noncoding RNA KCNMA1-AS1 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells by activating the SMAD9 signaling pathway
Authors: Mai Zhaoyi , Liu Jingpeng , Jiang Xiao , Gu Wenli , Wang Wei , Li Simin , Schmalz Gerhard , Xiao Hui , Zhao Jianjiang
Published: November 2023

The human bone marrow mesenchymal stem cells (hBMSCs) undergo intense osteogenic differentiation, a crucial bone formation mechanism. Evidence from prior studies suggested an association between long noncoding RNAs (lncRNAs) and the osteogenic differentiation of hBMSCs. However, precise roles and molecular mechanisms are still largely unknown. In this work, we report for the first time that lncRNA KCNMA1 antisense RNA 1 (KCNMA1-AS1) plays a vital role in regulating hBMSCs’ osteogenic differentiation. Here, it was observed that the KCNMA1-AS1 expression levels were significantly upregulated during osteogenic differentiation. In addition, KCNMA1-AS1 overexpression enhanced in vitro osteogenic differentiation of hBMSCs and in vivo bone formation, whereas knockdown of KCNMA1-AS1 resulted in the opposite result. Additionally, the interaction between KCNMA1-AS1 and mothers against decapentaplegic homolog 9 (SMAD9) was confirmed by an RNA pull-down experiment, mass spectrometry, and RIP assay. This interaction regulated the activation of the SMAD9 signaling pathway. Moreover, rescue assays demonstrated that the inhibitor of the SMAD9 signaling pathway reversed the stimulative effects on osteogenic differentiation of hBMSCs by KCNMA1-AS1 overexpression. Altogether, our results stipulate that KCNMA1-AS1 promotes osteogenic differentiation of hBMSCs via activating the SMAD9 signaling pathway and can serve as a biomarker and therapeutic target in treating bone defects.
High-throughput droplet microfluidics screening and genome sequencing analysis for improved amylase-producing Aspergillus oryzae
Authors: Li Qinghua , Lu Jinchang , Liu Jingya , Li Jianghua , Zhang Guoqiang , Du Guocheng , Chen Jian
Published: November 2023

Background

The exceptional protein secretion capacity, intricate post-translational modification processes, and inherent safety features of A. oryzae make it a promising expression system. However, heterologous protein expression levels of existing A. oryzae species cannot meet the requirement for industrial-scale production. Therefore, establishing an efficient screening technology is significant for the development of the A. oryzae expression system.

Results

In this work, a high-throughput screening method suitable for A. oryzae has been established by combining the microfluidic system and flow cytometry. Its screening efficiency can reach 350 droplets per minute. The diameter of the microdroplet was enlarged to 290 µm to adapt to the polar growth of A. oryzae hyphae. Through enrichment and screening from approximately 450,000 droplets within 2 weeks, a high-producing strain with α-amylase increased by 6.6 times was successfully obtained. Furthermore, 29 mutated genes were identified by genome resequencing of high-yield strains, with 15 genes subjected to editing and validation. Two genes may individually influence α-amylase expression in A. oryzae by affecting membrane-associated multicellular processes and regulating the transcription of related genes.

Conclusions

The developed high-throughput screening strategy provides a reference for other filamentous fungi and Streptomyces. Besides, the strains with different excellent characteristics obtained by efficient screening can also provide materials for the analysis of genetic and regulatory mechanisms in the A. oryzae expression system.
Resatorvid alleviates experimental inflammatory TMJOA by restraining chondrocyte pyroptosis and synovial inflammation
Authors: Liu Xin , Li Huimin , Feng Yaping , Guo Huilin , Li Yingjie , Ke Jin , Long Xing
Published: November 2023

Objectives

Innate immunity plays a significant role in the pathogenesis of temporomandibular joint osteoarthritis (TMJOA), which is characterized by synovial inflammation and condylar cartilage degradation. We are urged to investigate the impact of Resatorvid, a preventative drug that inhibits Toll-like receptor 4 (TLR4), on experimental inflammatory TMJOA pathology.

Methods

An intra-articular injection of complete Freund’s adjuvant (CFA) was used to induce an experimental inflammatory mouse TMJOA model, and TLR4 expression was identified by immunofluorescent labeling. Intraperitoneal injections of Resatorvid were administered to CFA-induced TMJOA mice, and the pathology of TMJOA animals with and without Resatorvid treatment was examined by H&E, Safranin-O/Fast Green, and TRAP staining, as well as micro-CT, immunohistochemistry, and immunofluorescence. The impact of Resatorvid on chondrocyte pyroptosis and macrophage inflammation was further investigated using ATDC5 chondrocytes and RAW264.7 macrophages pretreated with relevant antagonists.

Results

CFA-induced TMJOA mice revealed remarkable synovial inflammation, together with a time course of cartilage degradation and bone destruction, with TLR4 elevated in the synovium and condylar cartilage. Prophylactic treatment with Resatorvid mitigated synovial inflammation, cartilage degeneration, and bone destruction in CFA-induced TMJOA mice and downregulated MyD88/NF-κB expression. Ex vivo studies demonstrated that Resatorvid treatment alleviated NOD-like receptor protein 3 (NLRP3)-mediated chondrocyte pyroptosis and degeneration and relieved macrophage inflammation by preventing reactive oxygen species (ROS) production through NLRP3 signaling.

Conclusion

Prophylactic treatment with Resatorvid alleviates TMJOA pathology by inhibiting chondrocyte pyroptosis and degeneration, as well as ROS-induced macrophage inflammation, through TLR4/MyD88/NF-κB/NLRP3.
Intracranial progression of the epidermoid cyst to a white epidermoid cyst in a pediatric patient: a case report
Authors: Laverde-Reyes María Fernanda , Márquez Juan Camilo , Nasner Daniela , Granados-Sánchez Ana María , Castillo Luis Fernando
Published: November 2023

Background

Epidermoid cysts are rare benign lesions that originate from remnants of ectodermal epithelial tissue, particularly infrequent in the pediatric population. They exhibit characteristic imaging features, with occasional variations leading to the development of a “white” epidermoid cyst. This transformation results from the presence of protein and lipid material within the cyst, causing intrinsic hyperintensity in T1-weighted images, signal hypointensity in T2-weighted images, and a bright signal in diffusion-weighted imaging.

Case presentation

We describe the case of a 5-year-old Latina pediatric patient initially diagnosed with a typical epidermoid cyst. After 13 years of follow-up, this typical epidermoid cyst underwent a transformation, becoming a “white” epidermoid cyst.

Conclusions

Epidermoid cysts are rare intracranial lesions. The term “white epidermoid cyst” does not denote a variant; it represents a distinct transformation within an epidermoid cyst due to liquid and protein accumulation. This transformation should be considered in cases with specific imaging characteristics.
Acinetobacter baumannii: assessing susceptibility patterns, management practices, and mortality predictors in a tertiary teaching hospital in Lebanon
Authors: Itani Rania , Khojah Hani M. J. , Karout Samar , Rahme Deema , Hammoud Lara , Awad Reem , Abu-Farha Rana , Mukattash Tareq L. , Raychouni Hamza , El-Lakany Abdalla
Published: November 2023

Background

Acinetobacter baumannii is a major nosocomial pathogen capable of causing life-threatening infections. This bacterium is highly resistant to antibiotics and associated with high mortality rates. Therefore, this study aimed to evaluate A. baumannii's susceptibility patterns to antimicrobials, assess the appropriateness of the initiated antimicrobial therapy, determine the mortality rate, and identify predictors associated with mortality.

Methods

A retrospective observational study was conducted among patients infected with A. baumannii at a university hospital in Lebanon through the revision of medical records. Kaplan–Meier survival analysis and log-rank tests were used to analyze time-to-mortality. Binary logistic regression was performed to identify predictors of mortality.

Results

The records of 188 patients were screened, and 111 patients with A. baumannii infection were enrolled. Almost all isolates were resistant to carbapenem, and 43% of the isolates were extensively-drug resistant. Almost half of the patients received initial inappropriate antimicrobial therapy (n = 50, 45.1%). The 30-day mortality rate associated with A. baumannii infection was 71.2% (79/111). The time to mortality in patients who received inappropriate antimicrobial therapy (5.70 ± 1.07 days) was significantly shorter than in those who received appropriate antimicrobial therapy (12.43 ± 1.01 days, P < 0.01). Binary logistic regression revealed that inappropriate antimicrobial therapy (adjusted odds ratio [AOR] = 16.22, 95% CI 2.68–9.97, P = 0.002), mechanical ventilation (AOR = 14.72, 95% CI 3.27–6.61, P < 0.001), and thrombocytopenia (AOR = 8.82, 95% CI 1.12–9.75, P = 0.003) were more likely associated with mortality.

Conclusions

A. baumannii exhibits an alarming mortality rate among infected patients. Thrombocytopenia, mechanical ventilation, and inappropriate antibiotic administration are associated with mortality in patients infected with A. baumannii. The prompt initiation of appropriate antimicrobial therapy, infection control measures, and effective stewardship program are crucial to reduce the incidence of A. baumannii and improve the treatment outcomes.
Knee extension contracture with fixed anterior tibia subluxation treated with PCL release and quadricepsplasty: a case report
Authors: Kim Dong Woon , Mostowy Marcin , Pękala Przemyslaw A. , Bawor Michalina , Kennedy Nicholas I. , LaPrade Robert F. , Malinowski Konrad
Published: November 2023

58‐year‐old male presented with knee extension contracture (25°) with iatrogenic fixed anterior tibial subluxation. Consecutive arthroscopic arthrolysis, manipulation under anesthesia, and quadriceps‐Z‐plasty during one surgery failed to restore flexion. Therefore, shortened posterior cruciate ligament was released, which eliminated subluxation and allowed 115° flexion. Despite physiotherapy, flexion progressively decreased to 70° postoperatively. Revision quadricepsplasty by transverse incisions restored 120° of flexion maintained at 31‐months follow‐up. International Knee Documentation Committee increased 4/87‐ > 50/87, Knee injury and Osteoarthritis Outcome 7/100‐ > 68/100 at follow‐up. Posterior cruciate ligament release and repeated quadricepsplasty could be a viable salvage option in severe extension contracture with fixed anterior tibial subluxation.
Femoral head translation in borderline and definite dysplastic hips during weight‐bearing: 2D/3D image registration analysis
Authors: Sakai Shinichiro , Kutsuna Tatsuhiko , Kono Kohei , Kinoshita Tomofumi , Mashima Naohiko , Takao Masaki
Published: November 2023

Purpose

The aims of this study were to 1) assess femoral head translation during weight‐bearing in symptomatic developmental dysplasia of the hip (DDH) and 2) compare it between borderline DDH and definite DDH.

Methods

The study included four individuals with borderline DDH and nine with definite DDH, scheduled for periacetabular osteotomy. Anteroposterior X‐ray images of the hip joint were obtained in the standing position, and computed tomography images of the pelvis were obtained in the supine position. Femoral head translation from the supine to a standing position was measured using 2D/3D X‐ray image registration.

Results

From a supine to a standing position, the femoral head translated 0.3 mm laterally, 0.5 mm anteriorly, and 0.5 mm superiorly on average. The mean femoral head translation in 3D between the supine and standing positions was 1.5 mm. The 3D femoral head translation in the borderline DDH group was significantly greater than that in the definite DDH group. In the definite DDH group, there was a significant correlation between the center edge (CE) angle and 3D femoral head translation (ρ = ‐0.78, P = 0.012).

Conclusions

Symptomatic DDH showed femoral head translation in the anterior, lateral, and superior directions during weight‐bearing. In definite DDH, the amount of femoral head translation was negatively correlated with the CE angle. The amount of 3D translation in patients with borderline DDH was larger than that in definite DDH. Dynamic joint instability during weight‐bearing was observed in borderline DDH as well as definite DDH. Treatment to enhance joint stability during weight‐bearing is important in both cases.
Comparison of the LBM snowdrift model output with the observation results
Authors: Tanji Seika , Inatsu Masaru , Harada Yusuke
Published: November 2023

In this work, snowdrift experiments which are equivalent to one drifting snow event are performed by the snowdrift model. The model consisted of the computational fluid dynamics part of the large-eddy simulation with the lattice Boltzmann method and the drifting snow part of the conventional advection algorithm for representative Lagrangian particles. The observed vertical wind profile of a 4 h drifting snow event in Teshikaga Town was used as the inflow boundary conditions in the model to compare the results of the snowdrift estimated by the model and the observed snowdrift distribution. Parallelization enabled us to simulate the snowdrift distribution in a realistic domain and on the time scale of a single drifting snow event. We demonstrated that the upgraded model could quantitatively reproduce the height and position of the observed snowdrift along the center of a three-dimensional fence.