bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence, risk factors and multiple outcomes of treatment delay in Chinese patients with schizophrenia
Authors: Yu Yue-Hui , Lu Quan
Published: October 2023

Background

People with schizophrenia often delay treatment. This issue is not fully understood, particularly in low-and middle-income countries. This study aimed to elucidate the prevalence, risk factors and multiple outcomes of treatment delay in schizophrenia in a Chinese metropolis.

Methods

A two-stage whole cluster sampling survey was conducted in Beijing, China in 2020. A total of 1,619 patients with schizophrenia were included. Heterogeneity between groups and the changing trend of treatment delay were presented. Regression modelling methods were used to examine both the risk factors for treatment delay and related outcomes at individual and family levels.

Results

The median treatment delay for schizophrenia was 89 days (about 13 weeks). 49.35% surveyed patients delayed treatment for more than three months. Early age of onset, low level of education, living in well developed districts were important risk factors. Treatment delay in schizophrenia was significantly associated with patients’ poor medication adherence, comorbidity status and poor social functioning. It also increased the negative impact of the illness on families.

Conclusions

This study accumulated evidence of treatment delay in schizophrenia in China. It occurs even in the metropolis where mental health resources are relatively adequate. Further targeted interventions to raise public awareness should be crucial to reduce treatment delay.
Digital competence and psychological wellbeing in a social housing community: a repeated survey study
Authors: Buckingham Sarah , Tu Gengyang , Elliott Lewis , Poole Ria , Walker Tim , Bland Emma , Morrissey Karyn
Published: October 2023

Background

Little is known about whether digital competence is related to psychological wellbeing, with most previous research focusing on students and elderly people. There is also limited evidence on seasonal changes in psychological wellbeing, particularly in specific groups. Social housing residents are an underserved and under-researched population. The objectives of this study were to explore associations between digital competence (assessed by general technology self-efficacy) and psychological wellbeing (assessed by mental wellbeing and life satisfaction), and to explore seasonal effects, in social housing residents.

Methods

A repeated survey design was used. The Happiness Pulse questionnaire with a bespoke digital module was sent via post or e-mail at four timepoints between July 2021 and July 2022 to 167 social housing residents in West Cornwall, England. There were 110 respondents in total; thirty completed all four questionnaires and 59 completed an autumn/winter and summer questionnaire. Data were analysed using descriptive and inferential methods including regression, repeated measures analysis of variance and panel analysis.

Results

Significant positive associations were found between digital self-efficacy and mental wellbeing, and between digital self-efficacy and life satisfaction. However, there were no significant seasonal changes in psychological wellbeing.

Conclusions

The findings extend the existing literature beyond student and elderly populations and suggest that improving digital competence is a potential pathway to improving psychological wellbeing. Surveys with larger samples and qualitative studies are needed to elucidate the mechanisms involved.
BabyWASH and diarrhea prevention practices following multimedia educational intervention in hard-to-reach areas of the Afar and Somali regions of Ethiopia: a mixed-method endline evaluation
Authors: Negussie Abel , Lejore Ephrem , Hailemariam Ariam , Tefera Bereket , Mazengia Elyas Melaku , Dejene Tariku , Tadesse Yared , Adane Yimenu , Gugsa Kalkidan , Banda Kabuka , Sharma Rachana , Girma Eshetu
Published: October 2023

Background

Water, sanitation, and hygiene (WASH) interventions, which are specifically targeted towards young children—known as “BabyWASH”—reduce exposure to environmental contamination and prevent microbial burden in their play and feeding environments. The purpose of this endline study was to evaluate the effectiveness and potential sustainability of a multimedia educational intervention in influencing key BabyWASH and diarrhea prevention practices in four hard-to-reach woredas (i.e. administrative districts) of the Afar and Somali regions of Ethiopia.

Methods

A mixed-method, comparative cross-sectional study was conducted, which included 457 household surveys, 16 key informant interviews, and 8 focus group discussions. The multimedia educational intervention comprised: broadcasting radio talk shows and radio spot messages, capacity-building training for community health workers and community leaders, community mobilization campaigns, and the distribution of promotional print media materials. Propensity score matching analysis was used to estimate the effect of the multimedia educational intervention on key BabyWASH and diarrhea prevention attitudes and practices, which was then triangulated with qualitative findings.

Results

The multimedia intervention had a significant positive impact on good BabyWASH and diarrhea prevention practices, including appropriate practices of child feces disposal (t-test = 5.17; p < 0.001), handwashing with soap or ash (t-test = 8.85; p < 0.001), maintaining separate playgrounds for young children (t-test = 2.83; p < 0.001), washing of child’s body, hands, and faces (t-test = 15.78; p < 0.001), and food hygiene practices (t-test = 2.74; p < 0.05). The findings of the qualitative assessment also revealed that the multimedia intervention packages and the approaches used were successful in influencing key BabyWASH and diarrhea prevention behaviors in the intervention implementation woredas. In addition, providing capacity building training to local actors and community leaders and recording radio talk shows and sharing them with community members were recognized as effective intervention implementation strategies.

Conclusion

The endline evaluation found that the multimedia educational intervention improved awareness, perception, and practice of BabyWASH and diarrhea prevention behaviors in intervention woredas compared to control woredas. Sanitation and hygiene promotion interventions in pastoralist settings can be effective when using locally and contextually appropriate intervention strategies. However, considerations for integrating both behavioral and structural components in WASH interventions is essential.
Use and benefit of information, communication, and assistive technology among community-dwelling older adults – a cross-sectional study
Authors: Fotteler Marina L. , Kocar Thomas D. , Dallmeier Dhayana , Kohn Brigitte , Mayer Sarah , Waibel Ann-Kathrin , Swoboda Walter , Denkinger Michael
Published: October 2023

Background

Technology can support healthy aging and empower older adults to live independently. However, technology adoption by older adults, particularly assistive technology (AT), is limited and little is known about the types of AT used among older adults. This study explored the use of key information and communication technologies (ICT) and AT among community-dwelling adults aged ≥ 65.

Methods

A cross-sectional study was conducted among community-dwelling adults aged ≥ 65 in southern Germany using a paper-based questionnaire. The questionnaire included questions on the three domains sociodemographic aspects, health status, and technology use. Technology use was considered separately for key ICT (smartphone, computer/laptop, and tablet) and a range of 31 different AT. Data were analyzed using descriptive statistics, univariate analyses, and Bernoulli Naïve Bayes modelling.

Results

The questionnaire was answered by 616 participants (response rate: 24.64%). ICT were used by 497 (80.68%) participants and were associated with lower age, higher level of education, living together with someone, availability of internet connection, higher interest in technology, and better health status (p < .05). No association was found with sex and size of the hometown. The most frequently owned AT were a landline phone, a body scale, and a blood pressure monitor. Several AT related to functionality, (instrumental) activities of daily living- (IADL), and morbidity were used more frequently among non-ICT users compared to ICT-users: senior mobile phone (19.33% vs. 3.22%), in-house emergency call (13.45% vs. 1.01%), hearing aid (26.89% vs. 16.7%), personal lift (7.56% vs. 1.61%), electronic stand-up aid (4.2% vs. 0%). Those with higher interest in technology reported higher levels of benefit from technology use.

Conclusions

Despite the benefits older adults can gain from technology, its use remains low, especially among those with multimorbidity. Particularly newer, more innovative and (I)ADL-related AT appear underutilized. Considering the potential challenges in providing adequate care in the future, it may be crucial to support the use of these specific AT among older and frailer populations. To focus scientific and societal work, AT with a high impact on autonomy ((I)ADL/disease-related) should be distinguished from devices with a low impact on autonomy (household-/ comfort-related).
Interaction effect of midday napping duration and depressive symptoms on subjective memory impairment among older people in China: evidence from the China health and retirement longitudinal study database
Authors: Tang Li , Wang Ya-qi , Zhan Na-ni , Li Can-Yang , Zhuang Zhuang , Lyu Qi-yuan , Xiong Peng
Published: October 2023

Background

Subjective memory impairment (SMI) is common in older people. The aim of this study was to investigate the factors influencing SMI among older people in China, with specific focus on the interaction effect of midday napping duration and depressive symptoms on the risk of SMI.

Methods

Using a dataset representative of the Chinese population from a longitudinal study of health and retirement in China, subjects with SMI were screened using the question “how do you feel about your memory now?” and the Mini-Mental State Examination. A logistic regression model was applied to explore the factors affecting SMI. Additive and multiplicative models were used to analyze the interaction effect of midday napping duration and depressive symptoms on the risk of SMI.

Results

We enrolled 8,254 subjects included and the incidence of SMI was 63.9%. Depressive symptoms, nap time, and physical activity were influencing factors of SMI. Midday napping duration and depressive symptoms had positive additive interaction effects on the risk of SMI. When extended-length naps and depressive symptoms coexisted, the risk of SMI was 1.06 times greater than that for either alone (RERI, relative excess risk due to interaction = 0.27, 95% CI = 0.07–0.43; AP, attributable proportion = 0.14, 95% CI = 0.01–0.23; S, synergy index = 1.06, 95% CI = 0.57–1.62). When short naps and depressive symptoms coexisted, the risk of SMI was 1.2 times higher than that for either alone (RERI = 0.12, 95% CI=-0.14–0.39; AP = 0.13, 95% CI=-0.07–0.22; S = 1.20, 95% CI = 0.79–1.82).

Limitations

Since this was a cross-sectional study, the cause-and-effect relationships between the associated variables cannot be inferred.

Conclusions

The interaction effect that exists between nap time and depressive symptoms in older people is important for the identification and early intervention of people at risk for SMI.
Mortality in patients with interstitial lung diseases hospitalized by severe or critical COVID-19
Authors: Pruneda Ana Karem S. , Barreto-Rodríguez José Omar , Selman Moises , Juárez-Hernández Fortunato , Buendía-Roldán Ivette
Published: October 2023

Background

Since the first case of severe COVID-19, its effect on patients with previous interstitial lung disease (ILD) has been uncertain. We aimed to describe baseline clinical characteristics in ILD patients hospitalized by critical COVID and compare mortality during hospitalization.

Methods

We studied patients with ILD with COVID-19 and a control group matched by age, 1:2 ratio with COVID-19 without previous lung disease. On admission, laboratory tests and sociodemographic variables were evaluated. We evaluated patients critically ill and compared baseline characteristics and mortality in each group. Additionally, we performed a sub-analysis of ILD patients who died versus survivors.

Results

Forty-one patients and 82 controls were analyzed. In the group of ILD with COVID-19 there was a predominance of women (65 versus 33%: p < 0.001); lower leukocytes (9 ± 6 versus 11 ± 7, p = 0.01) and neutrophils (8 ± 5 versus 10 ± 6, p = 0.02). The most common ILD was secondary to autoimmune diseases. Patients with ILD and critical COVID-19 showed a significantly higher mortality compared with those without previous ILD (63 versus 33%, p = 0.007). Patients who died in this group had higher BMI (28 ± 6 versus 25 ± 4 kg/m2, p = 0.05), less extended hospital stay (20 ± 17 versus 36 ± 27 days, p = 0.01), and fewer days of evolution (9 ± 7 versus 16 ± 16, p = 0.05).

Conclusions

We found higher mortality in patients with ILD with critical COVID-19. Higher BMI and comorbidities were present in the non-survivors.
Predictors for post-traumatic hip osteoarthritis in patients with transverse acetabular fractures following open reduction internal fixation: a minimum of 2 years’ follow-up multicenter study
Authors: Li Junran , Jin Lin , Chen Chuanjie , Zhai Jingxiu , Li Ligeng , Hou Zhiyong
Published: October 2023

Background

The predictors of post-traumatic osteoarthritis (PTOA) in patients with transverse acetabular fractures (TAFs) following open reduction internal fixation (ORIF) remain unclear. This study aimed to investigate the risk factors for PTOA in TAFs after ORIF.

Methods

Data of TAF patients receiving ORIF were collected from January 2012 and February 2021. Patients suffered PTOA were classified as the osteoarthritis group (OG), while those without PTOA were classified as the non- osteoarthritis group (NG) with a minimum follow-up of 2 years. PTOA was diagnosed according to Tönnis OA classification during the period of follow-up. Univariate analysis, logistic regression analysis, and receiver operating characteristic (ROC) curve analyses were used to evaluate demographics, injury-related characteristics, perioperative and post-discharge information.

Results

Three hundred and eleven TAF patients were analyzed in this study, including 261 males and 50 females, with a mean age of 40.4 years (range 18 to 64 years). The incidence of PTOA was 29.6% (92 of 311) during the mean follow-up of 36.8 months (range 24 to 70 months). Several factors of PTOA were found using univariate analysis, including transverse fracture associated with posterior wall acetabular fracture (TPW-AF, p = 0.002), acetabular roof fracture (ARF, p = 0.001), femoral head lesion (FHL, p = 0.016), longer time from injury to surgery (TIS, p＜0.001) and physical work after surgery (PWAS, p＜0.001). Logistic regression analysis showed that TPW-AF (p = 0.007, OR = 2.610, 95%CI: 1.302–5.232), ARF (p = 0.001, OR = 2.887, 95%CI: 1.512–5.512), FHL (p = 0.005, OR = 2.302, 95%CI: 1.283–4.131), TIS (p<0.0001, OR = 1.294, 95%CI: 1.192–1.405) and PWAS (p<0.0001, 3.198, 95%CI: 1.765–5.797) were independent risk factors of PTOA. Furthermore, ROC curve analysis indicated 11.5 days as the cut-off values to predict PTOA.

Conclusions

Our findings identified that TPW-AF, ARF, FHL, TIS and PWAS were independent risk factors for PTOA in patients with TAFs following ORIF. It can help orthopedic surgeons to take early individualized interventions to reduce its incidence.
Association of smoking with cartilage loss of knee osteoarthritis: data from two longitudinal cohorts
Authors: Shen Ziyuan , Wang Yining , Xing Xing , Jones Graeme , Cai Guoqi
Published: October 2023

Background

Previous studies have been inconsistent concerning the association between smoking and risk of osteoarthritis (OA). This study aimed to explore the associations of smoking status and change in cartilage volume of OA in two longitudinal cohorts.

Methods

Subjects from the Osteoarthritis Initiative cohort (OAI, n = 593) and the Tasmanian Older Adult Cohort (TASOAC, n = 394) were included in this study. For both cohorts, participants were classified into three groups based on their smoking status, namely ‘never’, ‘former’, and ‘current’ smokers. The outcome measures were the annual rate of change of tibiofemoral cartilage volume over 2 years in OAI and of tibial cartilage volume over 2.6 years in TASOAC. Potential confounders were balanced using the inverse probability of treatment weighting (IPTW) method.

Results

Overall, 42.3% and 37.4% of participants were former smokers, and 5.7% and 9.3% were current smokers in the OAI and TASOAC cohorts, respectively. Compared to never smokers, neither former nor current smoking was associated with risk of the annual rate of change of tibiofemoral cartilage volume in OAI (former smoker: β=-0.068%/year, 95% confidence interval [CI] -0.824 to 0.688, p = 0.860; current smoker: β=-0.222%/year, 95% CI -0.565 to 0.120, p = 0.204) and tibial cartilage volume in TASOAC (former smoker: β = 0.001%/year, 95% CI -0.986 to 0.989, p = 0.998; current smoker: β=-0.839%/year, 95% CI -2.520 to 0.844, p = 0.329).

Conclusions

Our findings from two independent cohorts consistently showed that smoking was not associated with knee cartilage loss in older adults.
Iron deficiency and thyroid dysfunction among sudanese women in first trimester of pregnancy: a cross-sectional study
Authors: Abbas Wisal , Elmugabil Abdelmageed , Hamdan Hamdan Z. , Rayis Duria A. , Adam Ishag
Published: October 2023

Background

Pregnant women are more susceptible to iron deficiency (ID), and it can lead to several maternal and perinatal adverse effects. There are some published data on the effect of ID on thyroid function, but none of the studies were conducted in sub-Saharan African countries including Sudan. This study was conducted to investigate association between ID (ferritin < 15 µg/L) and thyroid functions [thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4)] among Sudanese women in the first trimester of pregnancy.

Method

A cross-sectional study was conducted in Saad Abuelela Maternity Hospital, Sudan. Obstetric/sociodemographic characteristics were gathered through questionnaires. Hemoglobin, serum ferritin, TSH, FT3, and FT4 were measured in all pregnant women. Continuous variables were compared with either independent sample t-test if they were normally distributed, or with Mann–Whitney U- test if they were not-normally distributed. Spearman correlations were performed between the continuous variables.

Results

In total, 127 pregnant women with mean [standard deviation (SD)] age of 27.0 (5.5) years and gestational age of 10.5 (3.0) weeks, respectively, were enrolled in this study. Forty-seven (37.0%) of these 127 women had ID. While the median [interquartile range (IQR)] of the parity, TSH, and FT3 were not different between women with ID and women without ID, the median (IQR) of FT4 was significantly lower in women with ID compared with women without ID [1.020 (0.910‒1.120) vs. 1.095 (0.990‒1.217) pmol, P = 0.014]. Serum ferritin was inversely correlated with FT3, (r = -0.225, P = 0.011). There was no significant correlation between serum ferritin, TSH, and FT4.

Conclusions

Iron deficiency was common during the first trimester of pregnancy and was associated with thyroid dysfunctions. Therefore, ID should be evaluated to avoid thyroid dysfunction.
Assessment of burnout level among clinical dental students during the COVID-19 pandemic
Authors: Korkmaz Cumhur , Dikicier Sibel , Atay Arzu
Published: October 2023

Background

The Coronavirus Disease (COVID-19) outbreak has caused especially health workers to face mental and physical problems all over the world. The aim of this study is to evaluate burnout, stress perception and perceived social support levels of clinical (the fourth and fifth year) dental students during the COVID-19 pandemic.

Methods

The Sociodemographic Information Form (SIF), Maslach Burnout Inventory (MBI), Sense of Coherence-13 (SoC-13), Perceived Stress Scale-10 (PSS-10), and Multidimensional Scale of Perceived Social Support (MSPSS) were used for data. Questionnaires were answered directly or online by the participants.

Results

A total of 211 participants, 67.8% were female, 32.2% were male. Of these, 96.2% were aged 20–24 years, 84.4% were nuclear family, 11.8% were extended family, and 3.8% were blended family, and 91.5% were willingly for dentistry choice. Based on the results; the total burnout score indicated moderate burnout (41.99 ± 9.94), the SoC-13 scale indicated a strong sense of coherence (55.24 ± 7.21), the PSS-10 score (22.44 ± 3.44) indicated moderate perceived stress and the MSPSS score (65.92 ± 13.22) indicated high perceived social support. A positive correlation was found between perceived stress and burnout. Based on the personal accomplishment subscale; females, those living in extended family, and those who unwillingly choose dentistry among the clinical dental students had higher intense burnout (p < 0.05).

Conclusions

The findings demonstrated that clinical dental students were affected by the emotional stress caused by the COVID-19 pandemic conditions. In the education of dentistry faculties, it would be appropriate to carry out comprehensive studies on adaptation to the changing living conditions with the COVID-19 pandemic and taking the necessary measures for the psychological distress caused by the difficulties experienced.
Intelligent identification system of gastric stromal tumors based on blood biopsy indicators
Authors: Han Shangjun , Song Meijuan , Wang Jiarui , Huang Yalong , Li Zuxi , Yang Aijia , Sui Changsheng , Zhang Zeping , Qiao Jiling , Yang Jing
Published: October 2023

Background

The most prevalent mesenchymal-derived gastrointestinal cancers are gastric stromal tumors (GSTs), which have the highest incidence (60–70%) of all gastrointestinal stromal tumors (GISTs). However, simple and effective diagnostic and screening methods for GST remain a great challenge at home and abroad. This study aimed to build a GST early warning system based on a combination of machine learning algorithms and routine blood, biochemical and tumour marker indicators.

Methods

In total, 697 complete samples were collected from four hospitals in Gansu Province, including 42 blood indicators from 318 pretreatment GST patients, 180 samples of gastric polyps and 199 healthy individuals. In this study, three algorithms, gradient boosting machine (GBM), random forest (RF), and logistic regression (LR), were chosen to build GST prediction models for comparison. The performance and stability of the models were evaluated using two different validation techniques: 5-fold cross-validation and external validation. The DeLong test assesses significant differences in AUC values by comparing different ROC curves, the variance and covariance of the AUC value.

Results

The AUC values of both the GBM and RF models were higher than those of the LR model, and this difference was statistically significant (P < 0.05). The GBM model was considered to be the optimal model, as a larger area was enclosed by the ROC curve, and the axes indicated robust model classification performance according to the accepted model discriminant. Finally, the integration of 8 top-ranked blood indices was proven to be able to distinguish GST from gastric polyps and healthy people with sensitivity, specificity and area under the curve of 0.941, 0.807 and 0.951 for the cross-validation set, respectively.

Conclusion

The GBM demonstrated powerful classification performance and was able to rapidly distinguish GST patients from gastric polyps and healthy individuals. This identification system not only provides an innovative strategy for the diagnosis of GST but also enables the exploration of hidden associations between blood parameters and GST for subsequent studies on the prevention and disease surveillance management of GST. The GST discrimination system is available online for free testing of doctors and high-risk groups at https://jzlyc.gsyy.cn/bear/mobile/index.html.
Perceptions and stress of conscience in relation to burnout among nursing staff in older people care settings: a cross sectional study
Authors: Nazari Shima , Norberg Astrid , Strandberg Gunilla , Åhlin Johan , Ericson-Lidman Eva , Mazaheri Monir
Published: October 2023

Background

Considering cultural influences, it is important to study the perceptions and stress of conscience in different contexts. This study aimed to investigate the association between perceptions of conscience, stress of conscience, and burnout among nursing staff working in older people care settings in Tehran.

Methods

This was a descriptive, cross-sectional study. A total of 161 participants completed the Perceptions of Conscience Questionnaire, Stress of Conscience Questionnaire, and Oldenburg Burnout Inventory, 2019. All nursing staff working at the 20 contacted nursing homes agreed to participate in the study. The descriptive and inferential analysis was conducted through SPSS, using T-tests and one-way between-groups analysis of variance, Chi-square and t-tests, Cohen's d (d), Eta-squared (η2), and Phi coefficient (φ), Partial least squares regression (PLSR), jackknife approximate t-tests of the regression coefficients, and jackknife 95% confidence intervals of the regression coefficients.

Results

The nursing staff perceived their conscience mainly as an authority, asset, and warning signal. Impact of workload on family life was the most common source of stress for the nursing staff. Dealing with incompatible demands, the impact of workload on family life, witnessing insulated patients, inability to meet one’s standards in providing care, and perception of conscience as a burden were strongly associated with the burnout.

Conclusions

Perceiving conscience as a warning signal or authority may serve as a buffer against burnout among nursing staff. This study highlights the need for further exploration of perceptions of conscience in different cultural and social backgrounds.
Rituximab for the treatment of relapsing-remitting multiple sclerosis in Thailand: an economic evaluation and budget impact analysis
Authors: Aungsumart Saharat , Turongkaravee Saowalak , Youngkong Sitaporn , Apiwattanakul Metha , Thakkinstian Ammarin , Chaikledkaew Usa
Published: October 2023

Background

Multiple sclerosis is an inflammatory demyelination process in the central nervous system (CNS) causing neurological disability and poor quality of life. Currently, Thai Food and Drug Administration (FDA)-approved disease-modifying therapy is costly, and most patients with multiple sclerosis are ineligible for treatment in Thailand as previous studies have challenged its cost-effectiveness. Off-label use of rituximab is inexpensive and highly effective in treating multiple sclerosis, but evidence of its cost-effectiveness in Thailand is yet to be collected.

Methods

This study aimed to evaluate the cost-utility and budget impact of rituximab for multiple sclerosis treatment compared with best supportive care, the standard practice in Thailand to treat the disease. A Markov model with a one-month cycle length and lifetime horizon was applied to compare the costs and outcomes of rituximab and best supportive care based on a societal perspective. Accordingly, incremental cost-effectiveness ratios were estimated. Probabilistic and one-way sensitivity analyses were conducted to investigate parameter uncertainty. In addition, the Markov model was used to assess the 5-year budget impact from the government perspective.

Results

A rituximab biosimilar demonstrated higher effectiveness and lower associated costs, compared to best supportive care, with the highest probability of being cost-effective (96%). The probability of relapse was the most sensitive parameter according to the one-way sensitivity analysis. The calculated budget impact of treating patients with multiple sclerosis in Thailand was 26,360,000 Thai baht (THB) or 844,255 United States dollars (USD) in the first fiscal year, and approximately 20,810,000–23,080,000 THB (666,608–739,388 USD) in the next four fiscal years.

Conclusion

In Thailand, a rituximab biosimilar would reduce the overall costs of multiple sclerosis treatment and should, therefore, be included in the National List of Essential Medicines.
Nr4a1 marks a distinctive ILC2 activation subset in the mouse inflammatory lung
Authors: Xu Shasha , Zhang Yu , Liu Xingjie , Liu Huisheng , Zou Xinya , Zhang Linlin , Wang Jing , Zhang Zhiwei , Xu Xiang , Li Mingxia , Li Kairui , Shi Shuyue , Zhang Ying , Miao Zhichao , Zha Jie , Yu Yong
Published: October 2023

Background

Group 2 innate lymphoid cells (ILC2s) are critical sources of type 2 cytokines and represent one of the major tissue-resident lymphoid cells in the mouse lung. However, the molecular mechanisms underlying ILC2 activation under challenges are not fully understood.

Results

Here, using single-cell transcriptomics, genetic reporters, and gene knockouts, we identify four ILC2 subsets, including two non-activation subsets and two activation subsets, in the mouse acute inflammatory lung. Of note, a distinct activation subset, marked by the transcription factor Nr4a1, paradoxically expresses both tissue-resident memory T cell (Trm), and effector/central memory T cell (Tem/Tcm) signature genes, as well as higher scores of proliferation, activation, and wound healing, all driven by its particular regulons. Furthermore, we demonstrate that the Nr4a1+ILC2s are restrained from activating by the programmed cell death protein-1 (PD-1), which negatively modulates their activation-related regulons. PD-1 deficiency places the non-activation ILC2s in a state that is prone to activation, resulting in Nr4a1+ILC2 differentiation through different activation trajectories. Loss of PD-1 also leads to the expansion of Nr4a1+ILC2s by the increase of their proliferation ability.

Conclusions

The findings show that activated ILC2s are a heterogenous population encompassing distinct subsets that have different propensities, and therefore provide an opportunity to explore PD-1's role in modulating the activity of ILC2s for disease prevention and therapy.
The neck as a keystone structure in avian macroevolution and mosaicism
Authors: Marek Ryan D. , Felice Ryan N.
Published: October 2023

Background

The origin of birds from non-avian theropod dinosaur ancestors required a comprehensive restructuring of the body plan to enable the evolution of powered flight. One of the proposed key mechanisms that allowed birds to acquire flight and modify the associated anatomical structures into diverse forms is mosaic evolution, which describes the parcelization of phenotypic traits into separate modules that evolve with heterogeneous tempo and mode. Avian mosaicism has been investigated with a focus on the cranial and appendicular skeleton, and as such, we do not understand the role of the axial column in avian macroevolution. The long, flexible neck of extant birds lies between the cranial and pectoral modules and represents an opportunity to study the contribution of the axial skeleton to avian mosaicism.

Results

Here, we use 3D geometric morphometrics in tandem with phylogenetic comparative methods to provide, to our knowledge, the first integrative analysis of avian neck evolution in context with the head and wing and to interrogate how the interactions between these anatomical systems have influenced macroevolutionary trends across a broad sample of extant birds. We find that the neck is integrated with both the head and the forelimb. These patterns of integration are variable across clades, and only specific ecological groups exhibit either head-neck or neck-forelimb integration. Finally, we find that ecological groups that display head-neck and neck-forelimb integration tend to display significant shifts in the rate of neck morphological evolution.

Conclusions

Combined, these results suggest that the interaction between trophic ecology and head-neck-forelimb mosaicism influences the evolutionary variance of the avian neck. By linking together the biomechanical functions of these distinct anatomical systems, the cervical vertebral column serves as a keystone structure in avian mosaicism and macroevolution.
Direct regulation of the cardiac ryanodine receptor (RyR2) by O-GlcNAcylation
Authors: Okolo Chidinma A , Khaing Ei-Phyo , Mereacre Valeria , Wallace Rachel S , Munro Michelle L , Erickson Jeffrey R , Jones Peter P.
Published: October 2023

Background

O-GlcNAcylation is the enzymatic addition of a sugar, O-linked β-N-Acetylglucosamine, to the serine and threonine residues of proteins, and is abundant in diabetic conditions. We have previously shown that O-GlcNAcylation can trigger arrhythmias by indirectly increasing pathological Ca2+ leak through the cardiac ryanodine receptor (RyR2) via Ca2+/calmodulin-dependent kinase II (CaMKII). However, RyR2 is well known to be directly regulated by other forms of serine and threonine modification, therefore, this study aimed to determine whether RyR2 is directly modified by O-GlcNAcylation and if this also alters the function of RyR2 and Ca2+ leak.

Methods

O-GlcNAcylation of RyR2 in diabetic human and animal hearts was determined using western blotting. O-GlcNAcylation of RyR2 was pharmacologically controlled and the propensity for Ca2+ leak was determined using single cell imaging. The site of O-GlcNAcylation within RyR2 was determined using site-directed mutagenesis of RyR2.

Results

We found that RyR2 is modified by O-GlcNAcylation in human, animal and HEK293 cell models. Under hyperglycaemic conditions O-GlcNAcylation was associated with an increase in Ca2+ leak through RyR2 which persisted after CaMKII inhibition. Conversion of serine-2808 to alanine prevented an O-GlcNAcylation induced increase in Ca2+ leak.

Conclusions

These data suggest that the function of RyR2 can be directly regulated by O-GlcNAcylation and requires the presence of serine-2808.
Microbial synthesis of the plant natural product precursor p-coumaric acid with Corynebacterium glutamicum
Authors: Mutz Mario , Kösters Dominic , Wynands Benedikt , Wierckx Nick , Marienhagen Jan
Published: October 2023

Background

Phenylpropanoids such as p-coumaric acid represent important precursors for the synthesis of a broad range of plant secondary metabolites including stilbenoids, flavonoids, and lignans, which are of pharmacological interest due to their health-promoting properties. Although extraction from plant material or chemical synthesis is possible, microbial synthesis of p-coumaric acid from glucose has the advantage of being less expensive and more resource efficient. In this study, Corynebacterium glutamicum was engineered for the production of the plant polyphenol precursor p-coumaric acid from glucose.

Results

Heterologous expression of the tyrosine ammonia-lyase encoding gene from Flavobacterium johnsoniae enabled the conversion of endogenously provided tyrosine to p-coumaric acid. Product consumption was avoided by abolishing essential reactions of the phenylpropanoid degradation pathway. Accumulation of anthranilate as a major byproduct was eliminated by reducing the activity of anthranilate synthase through targeted mutagenesis to avoid tryptophan auxotrophy. Subsequently, the carbon flux into the shikimate pathway was increased, phenylalanine biosynthesis was reduced, and phosphoenolpyruvate availability was improved to boost p-coumaric acid accumulation. A maximum titer of 661 mg/L p-coumaric acid (4 mM) in defined mineral medium was reached. Finally, the production strain was utilized in co-cultivations with a C. glutamicum strain previously engineered for the conversion of p-coumaric acid into the polyphenol resveratrol. These co-cultivations enabled the synthesis of 31.2 mg/L (0.14 mM) resveratrol from glucose without any p-coumaric acid supplementation.

Conclusions

The utilization of a heterologous tyrosine ammonia-lyase in combination with optimization of the shikimate pathway enabled the efficient production of p-coumaric acid with C. glutamicum. Reducing the carbon flux into the phenylalanine and tryptophan branches was the key to success along with the introduction of feedback-resistant enzyme variants.
EGCG inhibits the inflammation and senescence inducing properties of MDA-MB-231 triple-negative breast cancer (TNBC) cells-derived extracellular vesicles in human adipose-derived mesenchymal stem cells
Authors: Gonzalez Suarez Narjara , Fernandez-Marrero Yuniel , Hébert Mathieu P. A. , Roy Marie-Eve , Boudreau Luc H. , Annabi Borhane
Published: October 2023

Background

Triple-negative breast cancer (TNBC) cells’ secretome can induce a pro-inflammatory phenotype in human adipose-derived mesenchymal stem cells (hADMSC). This can be prevented by the green tea polyphenol epigallocatechin-3-gallate (EGCG). The impact of EGCG on the paracrine regulation that the extracellular vesicles (EVs) specifically exert within the TNBC secretome remains unknown.

Methods

EVs were obtained from a TNBC-derived serum-starved MDA-MB-231 cell model treated or not with EGCG under normoxic or hypoxic (< 1% O2) culture conditions. RNA-Seq analysis was used to assess the EVs’ genetic content. The modulation of inflammatory and senescence markers in hADMSC was evaluated by RT-qPCR using cDNA arrays and validated by immunoblotting. A protein profiler phospho-kinase array was used to explore signaling pathways.

Results

While hypoxic culture conditions did not significantly alter the genetic content of MDA-MB-231-secreted EVs, the addition of EGCG significantly modified EVs genetic material at low oxygen tension. Gene expression of cancer-associated adipocyte pro-inflammatory markersCXCL8,CCL2andIL-1βwas increased in hADMSC treated with EVs. Concomitantly, EVs isolated from MDA-MB-231 treated with EGCG (EGCG-EVs) downregulatedCCL2andIL-1β,while inducing higher expression ofCXCL8andIL-6levels. EVs activated CHK-2, c-Jun, AKT and GSK-3β signaling pathways in hADMSC, whereas EGCG-EVs specifically reduced the latter two as well as the serum starvation-induced senescence markers p21 and β-galactosidase. Finally, the mitochondrial content within the TNBC cells-derived EVs was found reduced upon EGCG treatment.

Conclusion

This proof of concept study demonstrates that the chemopreventive properties of diet-derived polyphenols may efficiently target the paracrine regulation that TNBC cells could exert upon their surrounding adipose tissue microenvironment.
Assessing caregivers’ perceptions of treatment-seeking for suspected severe malaria in the Democratic Republic of the Congo
Authors: Okitawutshu Jean , Tshefu Antoinette , Kalenga Jean-Claude , Delvento Giulia , Burri Christian , Hetzel Manuel W. , Lengeler Christian , Signorell Aita
Published: October 2023

Background

Malaria remains a major public health issue in the Democratic Republic of the Congo (DRC), accounting for 44% deaths among outpatient visits in children < 5 years of age, and 22% of facility deaths. Understanding determinants of caregivers’ treatment-seeking patterns and decision-making is crucial in reducing the malaria burden.

Methods

In the frame of the Community Access to Rectal Artesunate for Malaria (CARAMAL) project, cross-sectional household surveys that randomly sampled villages and households were carried-out in three rural DRC health zones prior to the rollout of pre-referral Rectal Artesunate (RAS) and then 9 and 19 months after RAS rollout (post-RAS). Data were captured electronically through face-to-face interviews with the main caregivers of children < 5 years. Capillary blood samples of the children were tested for malaria and anaemia. The main study outcome was whether caregiver “sought treatment outside home” when the child had fever. Multilevel mixed effects logistic regression models using village as random effect and health zone as a fixed effect was performed to assess treatment-seeking predictors.

Results

2439 household interviews were completed (pre-RAS 888 and post-RAS 1551), including 316 and 653 treatment-seeking interviews. Overall, 3499 children < 5 years were tested for malaria and anaemia (pre-RAS 1,315 and post-RAS 2184). Caregiver’s recognition of severe malaria signs was poor, while knowledge of symptoms of uncomplicated malaria seemed high. Despite this, danger signs significantly increased the odds of seeking treatment (aOR = 2.12, 95%CI 1.03–4.38), the same was found for the “least poor” quintile (aOR = 3.01, 95%CI 1.03–8.82), as well as residents of Kingandu (aOR = 2.78, 95%CI 1.01–7.65). “Doing something at home” against fever negatively affected treatment-seeking in both study phases. RAS acceptance was high, at almost 100%. Malaria prevalence was higher post-RAS (45.2%) compared to pre-RAS (34.4%), p = 0.003, but anaemia, although high (≥ 75%), was similar in both study phases (p = 0.92).

Conclusion

In remote communities with high malaria prevalence in the DRC, malaria remains a major problem. Improving the recognition of danger signs of severe disease and introducing pre-referral RAS may improve treatment-seeking and contribute to reducing malaria-related mortality among children—if quality of care can be guaranteed.
Deep learning for automated left ventricular outflow tract diameter measurements in 2D echocardiography
Authors: Zha Sigurd Zijun , Rogstadkjernet Magnus , Klæboe Lars Gunnar , Skulstad Helge , Singstad Bjørn-Jostein , Gilbert Andrew , Edvardsen Thor , Samset Eigil , Brekke Pål Haugar
Published: October 2023

Background

Measurement of the left ventricular outflow tract diameter (LVOTd) in echocardiography is a common source of error when used to calculate the stroke volume. The aim of this study is to assess whether a deep learning (DL) model, trained on a clinical echocardiographic dataset, can perform automatic LVOTd measurements on par with expert cardiologists.

Methods

Data consisted of 649 consecutive transthoracic echocardiographic examinations of patients with coronary artery disease admitted to a university hospital. 1304 LVOTd measurements in the parasternal long axis (PLAX) and zoomed parasternal long axis views (ZPLAX) were collected, with each patient having 1–6 measurements per examination. Data quality control was performed by an expert cardiologist, and spatial geometry data was preserved for each LVOTd measurement to convert DL predictions into metric units. A convolutional neural network based on the U-Net was used as the DL model.

Results

The mean absolute LVOTd error was 1.04 (95% confidence interval [CI] 0.90–1.19) mm for DL predictions on the test set. The mean relative LVOTd errors across all data subgroups ranged from 3.8 to 5.1% for the test set. Generally, the DL model had superior performance on the ZPLAX view compared to the PLAX view. DL model precision for patients with repeated LVOTd measurements had a mean coefficient of variation of 2.2 (95% CI 1.6–2.7) %, which was comparable to the clinicians for the test set.

Conclusion

DL for automatic LVOTd measurements in PLAX and ZPLAX views is feasible when trained on a limited clinical dataset. While the DL predicted LVOTd measurements were within the expected range of clinical inter-observer variability, the robustness of the DL model requires validation on independent datasets. Future experiments using temporal information and anatomical constraints could improve valvular identification and reduce outliers, which are challenges that must be addressed before clinical utilization.

Graphical Abstract
Establishment and verification of prediction model of occult peritoneal metastasis in advanced gastric cancer
Authors: Gao Hengfei , Ji Kangkang , Bao Linsen , Chen Hao , Lin Chen , Feng Min , Tao Liang , Wang Meng
Published: October 2023

Background

To investigate the risk factors associated with the development of occult peritoneal metastasis in advanced gastric cancer, and establish and externally validate a nomogram for predicting the occurrence of occult peritoneal metastasis in patients with advanced gastric cancer.

Methods

A total of 111 patients with advanced gastric cancer who underwent laparoscopic exploration or peritoneal lavage cytology examination at the Affiliated Drum Tower Hospital of Nanjing University Medical School from August 2014 to December 2021 were retrospectively analyzed. The patients diagnosed between 2019 and 2021 were assigned to the training set (n = 64), while those diagnosed between 2014 and 2016 constituted the external validation set (n = 47). In the training set, patients were classified into two groups based on preoperative imaging and postoperative pathological data: the occult peritoneal metastasis group (OPMG) and the peritoneal metastasis negative group (PMNG). In the validation set, patients were classified into the occult peritoneal metastasis group (CY1P0, OPMG) and the peritoneal metastasis negative group (CY0P0, PMNG) based on peritoneal lavage cytology results. A nomogram was constructed using univariate and multivariate analyses. The performance of the nomogram was evaluated using Harrell’s C-index, the area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), and calibration plots.

Results

This study analyzed 22 potential variables of OPM in 111 gastric cancer patients who underwent laparoscopic exploration or peritoneal lavage cytology examination. Logistic regression analysis results showed that Lauren classification, CLDN18.2 score and CA125 were independent risk factors for OPM in patients with gastric cancer. We developed a simple and easy-to-use prediction nomogram of occult peritoneal metastasis in advanced gastric cancer. This nomogram had an excellent diagnostic performance. The AUC of the bootstrap model in the training set was 0.771 and in the validation set was 0.711. This model showed a good fitting and calibration and positive net benefits in decision curve analysis.

Conclusion

We have developed a prediction nomogram of OPM for gastric cancer. This novel nomogram has the potential to enhance diagnostic accuracy for occult peritoneal metastasis in gastric cancer patients.