bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential cardiopulmonary haemodynamic phenotypes in PASC-related exercise intolerance
Authors: Kahn Peter A. , Joseph Phillip , Heerdt Paul M. , Singh Inderjit
Published: December 2023

Background

Post-acute sequelae of COVID-19 (PASC) affect a significant proportion of patients who have previously contracted SARS-CoV-2, with exertional intolerance being a prominent symptom. This study aimed to characterise the invasive haemodynamic abnormalities of PASC-related exertional intolerance using invasive cardiopulmonary exercise testing (iCPET).

Study design and intervention

55 patients were recruited from the Yale Post-COVID-19 Recovery Program, with most experiencing mild acute illness. Supine right heart catheterisation and iCPET were performed on all participants.

Main results

The majority (75%) of PASC patients exhibited impaired peak systemic oxygen extraction (pEO2) during iCPET in conjunction with supranormal cardiac output (CO) (i.e., PASC alone group). On average, the PASC alone group exhibited a “normal” peak exercise capacity,V′O2(89±18% predicted). ∼25% of patients had evidence of central cardiopulmonary pathology (i.e., 12 with resting and exercise heart failure with preserved ejection fraction (HFpEF) and two with exercise pulmonary hypertension (PH)). PASC patients with HFpEF (i.e., PASC HFpEF group) exhibited similarly impaired pEO2with well compensated PH (i.e., peakV′O2and CO >80% respectively) despite aberrant central cardiopulmonary exercise haemodynamics. PASC patients with HFpEF also exhibited increased body mass index of 39±7 kg·m−2. To examine the relative contribution of obesity to exertional impairment in PASC HFpEF, a control group comprising obese non-PASC group (n=61) derived from a historical iCPET cohort was used. The non-PASC obese patients with preserved peakV′O2(>80% predicted) exhibited a normal peak pulmonary artery wedge pressure (17±14versus25±6 mmHg; p=0.03) with similar maximal voluntary ventilation (90±12versus86±10% predicted; p=0.53) compared to PASC HFpEF patients. Impaired pEO2was not significantly different between PASC patients who underwent supervised rehabilitation and those who did not (p=0.19).

Conclusions

This study highlights the importance of considering impaired pEO2in PASC patients with persistent exertional intolerance unexplained by conventional investigative testing. Results of the current study also highlight the prevalence of a distinct high output HFpEF phenotype in PASC with a primary peripheral limitation to exercise.
Impact of preserved ratio impaired spirometry on coronary artery calcium score progression: a longitudinal cohort study
Authors: Im Yunjoo , Park Hye Yun , Lee Jin-Young , Kim Hyunsoo , Yoo Hongseok , Kang Mira , Cho Soo Jin , Hwang Jung Hye , Park Yong Bum , Cho Juhee , Kang Danbee , Shin Sun Hye
Published: December 2023

Background

Preserved ratio impaired spirometry (PRISm) is associated with increased cardiovascular disease (CVD) risk and mortality. However, a causal relationship between PRISm and CVD remains unclear. We investigated the progression of coronary artery calcium (CAC) scores based on the presence of PRISm and reduced forced vital capacity (FVC).

Methods

This retrospective cohort study included 11 420 participants aged ≥40 years with forced expiratory volume in 1 s (FEV1)/FVC ≥0.7 who underwent at least two health screening examinations with coronary computed tomography scan between 2003 and 2020, and were without a history of CVD or interstitial lung disease. Participants with PRISm, defined as FEV1/FVC ≥0.7 and FEV1<80% predicted, were further divided by low FVC (FVC <80% predicted). We estimated the 5-year progression rates of CAC by comparing participants with and without PRISm at baseline using mixed linear models.

Results

Of the 11 420 participants, 8536 (75%), 811 (7%) and 2073 (18%) had normal spirometry, PRISm with normal FVC and PRISm with low FVC, respectively. During the mean (range) follow-up of 6.0 (0.5–17.2) years, the multivariable adjusted ratio of 5-year CAC progression rates comparing participants with PRISm to those with normal spirometry was 1.08 (95% CI 1.04–1.13). This rate was higher in participants with PRISm with low FVC (1.21 (95% CI 1.12–1.30)) than in those with normal FVC.

Conclusion

In this longitudinal cohort study of subjects without a history of CVD, PRISm was significantly associated with CAC progression, which was more evident in the group with PRISm and low FVC.
Subtyping irritable bowel syndrome using cluster analysis: a systematic review
Authors: Zarei Diana , Saghazadeh Amene , Rezaei Nima
Published: December 2023

Background

Irritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder associated with a wide range of clinical symptoms. Some researchers have used cluster analysis (CA), a group of non-supervised learning methods that identifies homogenous clusters within different entities based on their similarity.

Objective and methods

This literature review aims to identify published articles that apply CA to IBS patients. We searched relevant keywords in PubMed, Embase, Web of Science, and Scopus. We reviewed studies in terms of the selected variables, participants’ characteristics, data collection, methodology, number of clusters, clusters’ profiles, and results.

Results

Among the 14 articles focused on the heterogeneity of IBS, eight of them utilized K-means Cluster Analysis (K-means CA), four employed Hierarchical Cluster Analysis, and only two studies utilized Latent Class Analysis. Seven studies focused on clinical symptoms, while four articles examined anocolorectal functions. Two studies were centered around immunological findings, and only one study explored microbial composition. The number of clusters obtained ranged from two to seven, showing variation across the studies. Males exhibited lower symptom severity and fewer psychological findings. The association between symptom severity and rectal perception suggests that altered rectal perception serves as a biological indicator of IBS. Ultra-slow waves observed in IBS patients are linked to increased activity of the anal sphincter, higher anal pressure, dystonia, and dyschezia.

Conclusion

IBS has different subgroups based on different factors. Most IBS patients have low clinical severity, good QoL, high rectal sensitivity, delayed left colon transit time, increased systemic cytokines, and changes in microbial composition, including increased Firmicutes-associated taxa and depleted Bacteroidetes-related taxa. However, the number of clusters is inconsistent across studies due to the methodological heterogeneity. CA, a valuable non-supervised learning method, is sensitive to hyperparameters like the number of clusters and random initialization of cluster centers. The random nature of these parameters leads to diverse outcomes even with the same algorithm. This has implications for future research and practical applications, necessitating further studies to improve our understanding of IBS and develop personalized treatments.
Cellstitch: 3D cellular anisotropic image segmentation via optimal transport
Authors: Liu Yining , Jin Yinuo , Azizi Elham , Blumberg Andrew J.
Published: December 2023

Background

Spatial mapping of transcriptional states provides valuable biological insights into cellular functions and interactions in the context of the tissue. Accurate 3D cell segmentation is a critical step in the analysis of this data towards understanding diseases and normal development in situ. Current approaches designed to automate 3D segmentation include stitching masks along one dimension, training a 3D neural network architecture from scratch, and reconstructing a 3D volume from 2D segmentations on all dimensions. However, the applicability of existing methods is hampered by inaccurate segmentations along the non-stitching dimensions, the lack of high-quality diverse 3D training data, and inhomogeneity of image resolution along orthogonal directions due to acquisition constraints; as a result, they have not been widely used in practice.

Methods

To address these challenges, we formulate the problem of finding cell correspondence across layers with a novel optimal transport (OT) approach. We propose CellStitch, a flexible pipeline that segments cells from 3D images without requiring large amounts of 3D training data. We further extend our method to interpolate internal slices from highly anisotropic cell images to recover isotropic cell morphology.

Results

We evaluated the performance of CellStitch through eight 3D plant microscopic datasets with diverse anisotropic levels and cell shapes. CellStitch substantially outperforms the state-of-the art methods on anisotropic images, and achieves comparable segmentation quality against competing methods in isotropic setting. We benchmarked and reported 3D segmentation results of all the methods with instance-level precision, recall and average precision (AP) metrics.

Conclusions

The proposed OT-based 3D segmentation pipeline outperformed the existing state-of-the-art methods on different datasets with nonzero anisotropy, providing high fidelity recovery of 3D cell morphology from microscopic images.
The antennal transcriptome analysis and characterizations of odorant-binding proteins in Megachile saussurei (Hymenoptera, Megachilidae)
Authors: Li Wei-Zhen , Kang Wen-Juan , Zhou Jing-Jiang , Shang Su-Qin , Shi Shang-Li
Published: December 2023

Background

Odorant-binding proteins (OBPs) are essential in insect’s daily behaviors mediated by olfactory perception. Megachile saussurei Radoszkowski (Hymenoptera, Megachilidae) is a principal insect pollinating alfalfa (Medicago sativa) in Northwestern China. The olfactory function have been less conducted, which provides a lot of possibilities for our research.

Results

Our results showed that 20 OBPs were identified in total. Multiple sequence alignment analysis indicated MsauOBPs were highly conserved with a 6-cysteine motif pattern and all belonged to the classic subfamily, coding 113-196 amino acids and sharing 41.32%-99.12% amino acid identity with known OBPs of other bees. Phylogenetic analysis indicated there were certain homologies existed among MsauOBPs and most sequences were clustered with that of Osmia cornuta (Hymenoptera, Megachilidae). Expression analysis showed the identified OBPs were mostly enriched in antennae instead of other four body parts, especially the MsauOBP2, MsauOBP3, MsauOBP4, MsauOBP8, MsauOBP11 and MsauOBP17, in which the MsauOBP2, MsauOBP4 and MsauOBP8 presented obvious tissue-biased expression pattern. Molecular docking results indicated MsauOBP4 might be the most significant protein in recognizing alfalfa flower volatile 3-Octanone, while MsauOBP13 might be the most crucial protein identifying (Z)-3-hexenyl acetate. It was also found the lysine was a momentous hydrophilic amino acid in docking simulations.

Conclusion

In this study, we identified and analyzed 20 OBPs of M. saussurei. The certain homology existed among these OBPs, while some degree of divergence could also be noticed, indicating the complex functions that different MsauOBPs performed. Besides, the M. saussurei and Osmia cornuta were very likely to share similar physiological functions as most of their OBPs were clustered together. MsauOBP4 might be the key protein in recognizing 3-Octanone, while MsauOBP13 might be the key protein in binding (Z)-3-hexenyl acetate. These two proteins might contribute to the alfalfa-locating during the pollination process. The relevant results may help determine the highly specific and effective attractants for M. saussurei in alfalfa pollination and reveal the molecular mechanism of odor-evoked pollinating behavior between these two species.
The effect of environmental factors on the genetic differentiation of Cucurbita ficifolia populations based on whole-genome resequencing
Authors: He Shuilian , Li Gengyun , Zhang Jing , Ding Yumei , Wu Hongzhi , Xie Junjun , Wu Hang , Yang Zhengan
Published: December 2023

Background

Cucurbita ficifolia is one of the squash species most resistant to fungal pathogens, and has especially high resistance to melon Fusarium wilt. This species is therefore an important germplasm resource for the breeding of squash and melon cultivars.

Results

Whole-genome resequencing of 223 individuals from 32 populations in Yunnan Province, the main cucurbit production area in China, was performed and 3,855,120 single-nucleotide polymorphisms (SNPs) and 1,361,000 InDels were obtained. SNP analysis suggested that levels of genetic diversity in C. ficifolia were high, but that different populations showed no significant genetic differentiation or geographical structure, and that individual C. ficifolia plants with fruit rinds of a similar color did not form independent clusters. A Mantel test conducted in combination with geographical distance and environmental factors suggested that genetic distance was not correlated with geographical distance, but had a significant correlation with environmental distance. Further associations between the genetic data and five environmental factors were analyzed using whole-genome association analysis. SNPs associated with each environmental factor were investigated and genes 250 kb upstream and downstream from associated SNPs were annotated. Overall, 15 marker-trait-associated SNPs (MTAs) and 293 genes under environmental selection were identified. The identified genes were involved in cell membrane lipid metabolism, macromolecular complexes, catalytic activity and other related aspects. Ecological niche modeling was used to simulate the distribution of C. ficifolia across time, from the present and into the future. We found that the area suitable for C. ficifolia changed with the changing climate in different periods.

Conclusions

Resequencing of the C. ficifolia accessions has allowed identification of genetic markers, such as SNPs and InDels. The SNPs identified in this study suggest that environmental factors mediated the formation of the population structure of C. ficifolia in China. These SNPs and Indels might also contribute to the variation in important pathways of genes for important agronomic traits such as yield, disease resistance and stress tolerance. Moreover, the genome resequencing data and the genetic markers identified from 223 accessions provide insight into the genetic variation of the C. ficifolia germplasm and will facilitate a broad range of genetic studies.
Better performance for right-skewed data using an alternative gamma model
Authors: Veazie Peter , Intrator Orna , Kinosian Bruce , Phibbs Ciaran S.
Published: December 2023

Background

The Maximum Likelihood Estimator (MLE) for parameters of the gamma distribution is commonly used to estimate models of right-skewed variables such as costs, hospital length of stay, and appointment wait times in Economics and Healthcare research. The common specification for this estimator assumes the variance is proportional to the square of the mean, which underlies estimation and specification tests. We present a specification in which the variance is directly proportional to the mean.

Methods

We used simulation experiments to investigate finite sample results, and we used United States Department of Veterans Affairs (VA) healthcare cost data as an empirical example comparing the fit and predictive ability of the models.

Results

Simulation showed the MLE based on a correctly specified alternative has less parameter bias, lower standard errors, and less skewness in distribution than a misspecified standard model. The application to VA healthcare cost data showed the alternative specification can have better R square, smaller root mean squared error, and smaller mean residuals within deciles of predicted values.

Conclusions

The alternative gamma specification can be a useful alternative to the standard specification for estimating models of right-skewed continuous variables.
Effect of different types of supervised exercise programs on cardiorespiratory and muscular fitness, pain, fatigue, mental health and inflammatory and oxidative stress biomarkers in older patients with post-COVID-19 sequelae “EJerSA-COVID-19”: a randomized controlled trial
Authors: Pleguezuelos Eulogio , Sánchez-Nuño Sergio , Del Carmen Amin , Serra-Payá Noemí , Moreno Eva , Molina-Raya Lorena , Robleda Gemma , Benet Marta , Santos-Ruiz Susana , Garrido Ainoa Biurrun , Jerez-Molina Carmen , Miravitlles Marc , Serra-Prat Mateu , Viñals Xavier , Farrés Montserrat Girabent , Carbonell Teresa , Garnacho-Castaño Manuel V.
Published: December 2023

Background

Many patients with COVID-19 present the so-called post-acute sequelae of COVID-19 such as fatigue, post-stress discomfort, dyspnea, headache, pain mental impairment, incapacity to perform daily physical tasks ant exercise intolerance. This study aims to investigate the effects of different exercise programs on physical and mental fitness, physical condition and biomarkers of the immune system and oxidative stress in older patients with post-COVID-19 sequelae.

Methods

The sample will be made up of 120 eligible participants, over the age of 60 years who have had COVID-19 disease and are survivors and present persistent COVID-19 symptomatology diagnosed by the corresponding physician. The participants will be randomly assigned to the experimental groups: supervised endurance group (SEG, n = 30), supervised strength group (SSG, n = 30), supervised concurrent group (SCG, n = 30), which will perform the corresponding exercise program 3 days a week compared to the control group (CG, n = 30), which will not carry out a supervised exercise program. The design of this project will include measurements of four relevant dimensions; 1) Cardiorespiratory fitness; 2) Muscle fitness; 3) Pain and mental health; and 4) Biomarkers of inflammation and oxidative stress.

Conclusions

The results of this study will provide insights into the effects of different exercise programs on physical and mental fitness, physical condition and biomarkers of the immune system and oxidative stress in older patients with post-COVID-19 sequelae. These findings may be the basis for the formulation of health plans and rehabilitation programs that allow healthy aging and a reduction in the associated morbidity in patients with post-COVID-19 sequelae.

Trial registration

NCT05848518. Registered on May 8, 2023.
Meta-analysis of outcomes following intravenous thrombolysis in patients with ischemic stroke on direct oral anticoagulants
Authors: Behnoush Amir Hossein , Khalaji Amirmohammad , Bahiraie Pegah , Gupta Rahul
Published: December 2023

Background

There has been debate on the use of intravenous thrombolysis (IVT) in patients with ischemic stroke and the recent use of direct oral anticoagulants (DOACs). Studies have compared these patients with non-DOAC groups in terms of outcomes. Herein, we aimed to systematically investigate the association between DOAC use and IVT’s efficacy and safety outcomes.

Results

A comprehensive systematic search was performed in PubMed, Embase, Scopus, and the Web of Science for the identification of relevant studies. After screening and data extraction, a random-effect meta-analysis was performed to calculate the odds ratio (OR) and 95% confidence interval (CI) for comparison of outcomes between patients on DOAC and controls. Six studies were included in the final review. They investigated a total of 254,742 patients, among which 3,499 had recent use of DOACs. The most commonly used DOACs were rivaroxaban and apixaban. The patients on DOAC had significantly higher rates of atrial fibrillation, hypertension, diabetes, and smoking. Good functional outcome defined by modified Rankin Scale (mRS) 0–2 was significantly lower in patients who received DOACs (OR 0.71, 95% CI 0.62 to 0.81, P < 0.01). However, in the subgroup analysis of 90-day mRS 0–2, there was no significant difference between groups (OR 0.71, 95% 0.46 to 1.11, P = 0.14). All-cause mortality was not different between the groups (OR 1.02, 95% CI 0.68 to 1.52, P = 0.93). Similarly, there was no significant difference in either of the in-hospital and 90-day mortality subgroups. Regarding symptomatic intracranial hemorrhage (sICH), the previous DOAC use was not associated with an increased risk of bleeding (OR 0.98, 95% CI 0.69 to 1.39, P = 0.92). A similar finding was observed for the meta-analysis of any ICH (OR 1.15, 95% CI 0.94 to 1.40, P = 0.18).

Conclusions

Based on our findings, IVT could be considered as a treatment option in ischemic stroke patients with recent use of DOACs since it was not associated with an increased risk of sICH, as suggested by earlier studies. Further larger studies are needed to confirm these findings and establish the safety of IVT in patients on DOAC.
Clinical value of ultrasonic indicators in predicting the outcome of caesarean scar pregnancy after pregnancy termination
Authors: Fu Liye , Yuan Hongxia , Cao Hong , Zhou Qichang , Tan Xiaotan , Guo Jun
Published: December 2023

Background

To investigate the predictive value of ultrasound indicators in early pregnancy for the outcome of caesarean scar pregnancy (CSP) after pregnancy termination.

Methods

This study retrospectively analysed the ultrasound images of 98 CSP patients who underwent transabdominal ultrasound-guided hysteroscopic curettage during early pregnancy at Changsha Hospital for Maternal and Child Health Care between January 2017 and October 2021. Patients were equally divided into a case group and a control group. The case group included 49 CSP patients with postoperative complications, such as intraoperative blood loss ≥ 200 ml or retained products of conception (RPOC). The remaining 49 CSP patients, with similar age and gestational age and with good postoperative outcomes, such as intraoperative blood loss ≤ 50 ml and no RPOC, were included in the control group. CSP was classified into three types according to the location of the gestational sac (GS) relative to the uterine cavity line (UCL) and serosal contour. Differences in ultrasound indicators between the case and control group were compared.

Results

There were significant differences between the case and control groups in the mean gestational sac diameter (MGSD), residual myometrium thickness (RMT) between the GS and the bladder, blood flow around the GS at the site of the previous caesarean incision, and types of CSP (P < 0.05). The rs of each ultrasound indicator were as follows: 0.258, -0.485, 0.369, 0.350. The optimal threshold for predicting good postoperative outcomes, such as intraoperative blood loss ≤ 50 ml and no RPOC, by receiver operating characteristic (ROC) curve analysis of the RMT was 2.3 mm.

Conclusion

Our findings show that the RMT, blood flow around the GS at the site of the previous caesarean incision, and types of CSP have a low correlation with postoperative complications, such as intraoperative blood loss ≥ 200 ml or RPOC, of early pregnancy termination in patients with CSP. To some extent, this study may be helpful for clinical prognostic prediction of patients with CSP and formulation of treatment strategies. Given the low correlation between these three indicators and postoperative complications, further studies are needed to identify indicators that can better reflect the postoperative outcomes of CSP patients.
An exploratory qualitative study of the psychological effects of HIV diagnosis; the need for early involvement of mental health professionals to improve linkage to care
Authors: Ninnoni Jerry Paul , Nsatimba Frederick , Agyemang Sampson Opoku , Commey Isaac Tetteh , Bennin Lydia , Agyare Elizabeth , Gyimah Leveana , Senya Kafui , Baddoo Nyonuku Akosua , Obiri-Yeboah Dorcas
Published: December 2023

Background

Diagnosing a life-threatening disease like the human immunodeficiency virus (HIV) can be unbearable to the individual, which has implications for their subsequent care-seeking decision-making. However, an essential element of HIV testing is identifying infected individuals and linking them with adequate care services, thus contributing to the UNAIDS 95-95-95 targets. The attainment of these targets has been particularly challenging for lower and middle-income countries (LMIC). This study explored the psychological reactions to a positive HIV status in a hospital treatment centre to provide insight into mental health interventions’ role in improving HIV screening and early antiretroviral therapy (ART) initiation to enhance the quality of life.

Methods

An exploratory qualitative study was investigated among adults who were diagnosed as HIV positive. Participants were purposively recruited from an HIV Treatment Centre. Data were collected with semi-structured interviews that explored the interpretations and psychological reactions to their positive HIV status. Overall, 18 participants were interviewed to reach saturation. Data were transcribed verbatim and analysed thematically to produce findings that address the study’s objective.

Results

Following analysis of participants’ interpretations, understanding and implications of their HIV-positive diagnosis, two major themes emerged: (1) anxiety regarding the impact of the disease on self, family and society was overwhelming. Participants were anxious because of the stigma, fear, worry, shock, and shame they faced. (2) Participants expressed hopelessness and could not see meaning or purpose in life. Suicidal ideation, suicide plans and self-harm characterised hopelessness.

Conclusions

The initial reaction to the diagnosis of HIV in this LMIC context has the potential to impact linkage to care negatively and, thus, the attainment of the global 95-95-95 targets. It is, therefore, essential that mental health and psychological support services are integrated with testing services to manage the initial reactions and support individuals to improve early linkage to care and thus improve overall outcomes for the infected individual and society.
Determinants of high-risk fertility behavior among women of reproductive age in Kenya: a multilevel analysis based on 2022 Kenyan demographic and health survey
Authors: Seifu Beminate Lemma , Tebeje Tsion Mulat , Asgedom Yordanos Sisay , Asmare Zufan Alamrie , Asebe Hiwot Altaye , Kase Bizunesh Fantahun , Shibeshi Abdu Hailu , Sabo Kebede Gemeda , Fente Bezawit Melak , Mare Kusse Urmale
Published: December 2023

Background

Women’s high-risk fertility behavior (HRFB), which is characterized by narrow birth intervals, high birth order, and younger maternal age at birth, have been scientifically reported to have detrimental effects on the mother and child’s health. To date, there has been limited research into the underlying factors contributing to high-risk fertility behavior in Kenya. Thus, the aim of this study is to identify the factors associated with high-risk fertility behavior among women of reproductive age in Kenya.

Method

The 2022 Kenyan Demography and Health Survey data was used for the current study. This study included 15,483 women of reproductive age. To account for the clustering effects of DHS data and the binary nature of the outcome variable, a multilevel binary logistic regression model was applied. An adjusted odds ratio with a 95% confidence interval was reported to declare the statistical significance. In addition, the model that had the lowest deviance was the one that best fit the data.

Results

The overall prevalence of HRFB among Kenyan women were 70.86% (95%CI = 69.96, 71.40). Women with primary, secondary, and higher educational levels, Protestant and Muslim religion followers, women whose husbands/partners had secondary and higher educational levels, a high household wealth index, ever had a terminated pregnancy, and rural residence, all of these factors were found to be strongly associated with high-risk fertility behavior.

Conclusion

As per the findings of our study, in Kenya a significant proportion of women has experienced HRFB. This is a matter of concern as it poses a significant challenge to the healthcare system. The high prevalence of HRFB indicates that there is an urgent need to take appropriate measures in order to mitigate its impact. The situation calls for a comprehensive and coordinated approach involving all stakeholders to address this issue effectively. It would benefit policymakers to create programs that consider factors like education, wealth, and residence that make women more susceptible to HRFB. Targeting women living in high HRFB-prevalence areas could help address the root causes of the issue. This approach can alleviate negative impacts and ensure effective and sustainable solutions.
Challenges of accessing hygiene facilities when on the move: an exploratory interview study with UK mobile workers
Authors: Rutter Sophie , Madden Andrew , White Lauren
Published: December 2023

Background

Access to hygiene facilities is essential for health and well-being, and in many countries, employers are legally obliged to ensure that hygiene facilities are readily available. This interview study considers how being on the move impacts the ability of mobile workers (such as community care workers, police, delivery drivers, gardeners, cleaners, utility workers) to access hygiene facilities, and the challenges they face.

Methods

Using a qualitative exploratory research design, we investigate through semi-structured interviews with 22 United Kingdom (UK) mobile workers (1) what influences their access to hygiene facilities, (2) their hygiene needs, and (3) where mobile workers are accessing hygiene facilities. The interview data was analysed qualitatively using a coding framework developed from a literature review of hand hygiene in fixed workplaces.

Results

Mobile workers’ access to hygiene facilities is influenced by the wider cultural environment, the biological environment, the organisational environment, the physical environment, the facility owner, the worker’s role, and the individual themselves, all underpinned by social norms. Our participants needed hygiene facilities so they could use the toilet, clean themselves, and do their work, and for First Aid. Access to facilities is challenging, and our participants needed to access facilities where they were working, travel to find them, or use hygiene kits. The quality of facilities is frequently poor, and mobile workers must often seek permission and may incur financial costs. Our participants often had to rely on the goodwill of people in private homes. In the absence of facilities, workers often resort to strategies that may affect their health (such as restricting drinking and eating, and ignoring urges) or their dignity (such as relieving themselves outdoors or even soiling their clothes).

Conclusions

The lack of hygiene facilities available to mobile workers is a serious health and well-being concern. Given that there are many occupations where workers are mobile at least some of the time, the scale of the problem needs to be recognised. This study adds to our understanding of hygiene in workplaces and highlights the inadequacy of current legislation, which appears to serve primarily those working in fixed workplaces such as offices. Recommendations are made to policy makers and organisations.
Establishment of a prognosis prediction model for lung squamous cell carcinoma related to PET/CT: basing on immunogenic cell death-related lncRNA
Authors: Han Yu , Dong Zhiqiang , Xing Yu , Zhan Yingying , Zou Jinhai , Wang Xiaodong
Published: December 2023

Background

Immunogenic cell death (ICD) stimulates adaptive immunity and holds significant promise in cancer therapy. Nevertheless, the influence of ICD-associated long non-coding RNAs (lncRNAs) on the prognosis of patients with lung squamous cell carcinoma (LUSC) remains unexplored.

Methods

We employed data from the The Cancer Genome Atlas (TCGA)database to identify ICD-related lncRNAs associated with the prognosis of LUSC using univariate Cox regression analysis. Subsequently, we utilized the LOSS regression model to construct a predictive risk model for assessing the prognosis of LUSC patients based on ICD-related lncRNAs. Our study randomly allocated187 TCGA patients into a training group and 184 patients for testing the predictive model. Furthermore, we conducted quantitative polymerase chain reaction (qPCR) analysis on 43 tumor tissues from LUSC patients to evaluate lncRNA expression levelsPearson correlation analysis was utilized to analyze the correlation of risk scores with positron emission tomography/computed tomography (PET/CT) parameters among LUSC patients.

Results

The findings from the univariate Cox regression revealed 16 ICD-associated lncRNAs linked to LUSC prognosis, with 12 of these lncRNAs integrated into our risk model utilizing the LOSS regression. Survival analysis indicated a markedly higher overall survival time among patients in the low-risk group compared to those in the high-risk group. The area under the Receiver operating characteristic (ROC) curve to differentiate high-risk and low-risk patients was 0.688. Additionally, the overall survival rate was superior in the low-risk group compared to the high-risk group. Correlation analysis demonstrated a positive association between the risk score calculated based on the ICD-lncRNA risk model and the maximum standard uptake value (SUVmax) (r = 0.427, P = 0.0043) as well as metabolic volume (MTV)of PET-CT (r = 0.360, P = 0.0177) in 43 LUSC patients.

Conclusion

We have successfully developed a risk model founded on ICD-related lncRNAs that proves effective in predicting the overall survival of LUSC patients.
Integrated bioinformatics and network pharmacology to explore the therapeutic target and molecular mechanisms of Bailing capsule on polycystic ovary syndrome
Authors: Guan Hao-ru , Li Bo , Zhang Ze-hua , Wu Han-song , He Xing-lishang , Dong Ying-jie , Su Jie , Lv Gui-yuan , Chen Su-hong
Published: December 2023

Background

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder that is common in women of reproductive age. The clinical features of PCOS include hyperandrogenemia and polycystic ovarian changes. Bailing capsule (BL), a proprietary Chinese medicine that contains fermented Cordyceps sinensis powder, has been applied to treat PCOS. However, the specific active ingredients of BL and its mechanisms of action are yet to be elucidated.

Methods

Initially, the effectiveness of BL on PCOS model mice was evaluated. Subsequently, the active ingredients of BL were searched in the TCMSP and TCM Systems Pharmacology databases, and their targets were predicted using Swiss Target Prediction and SEA databases. Furthermore, the GEO gene database was used to screen for differentially expressed genes (DEGs) related to PCOS. Data from Gene Card, OMIM, DDT, and Drugbank databases were then combined to establish a PCOS disease gene library. Cross targets were imported into the STRING database to construct a protein–protein interaction network. In addition, GO and KEGG pathway enrichment analyses were performed using Metascape and DAVID databases and visualized using Cytoscape software and R 4.2.3. The core targets were docked with SYBYL-X software, and their expressions in PCOS mice were further verified using qPCR.

Results

The core active ingredients of BL were identified to be linoleyl acetate, cholesteryl palmitate, arachidonic acid, among others. Microarray data sets from four groups containing disease and normal samples were obtained from the GEO database. A total of 491 DEGs and 106 drug–disease cross genes were selected. Estrous cycle and ovarian lesions were found to be improved in PCOS model mice following BL treatment. While the levels of testosterone, progesterone, and prolactin decreased, that of estradiol increased. qPCR findings indicated that the expressions of JAK2, PPARG, PI3K, and AKT1 were upregulated, whereas those of ESR1 and IRS1 were downregulated in PCOS model mice. After the administration of BL, the expressions of associated genes were regulated. This study demonstrated that BL exerted anti-PCOS effects via PIK3CA, ESR1, AKT, PPARG, and IRS1 targets affecting PI3K-Akt signaling pathways.

Discussion

This research clarified the multicomponent, multitarget, and multichannel action of BL and provided a theoretical reference for further investigations on its pharmacological basis and molecular mechanisms against PCOS.
Associations of dichlorophenol with metabolic syndrome based on multivariate-adjusted logistic regression: a U.S. nationwide population-based study 2003-2016
Authors: Cai Jing , Yang Zhichao , Zhao Sen , Ke Xing
Published: December 2023

Background

Para-dichlorobenzene (p-DCB) exposure associated with oxidative stress has indeed raised public concerns. However, whether p-DCB is linked with metabolic syndrome (MetS) remains unclear. We hypothesized that higher exposure to p-DCB would be linked with a higher risk of MetS in the U.S population. This study aimed to examine the associations of exposure to p-DCB with MetS prevalence.

Methods

We included 10,428 participants (5,084 men and 5,344 women), aged ≥ 20 years, from the National Health and Nutrition Examination Survey (2003–2016). The cases of MetS were diagnosed by NCEP/ATPIII. Logistic regression models were conducted to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of MetS prevalence. Moreover, the mix associations of p-DCB metabolites were assessed using quantile sum (WQS) regression and quantile g-computation (qgcomp) methods.

Results

We documented 2,861 (27.1%) MetS cases. After adjustment for the potential risk factors, the ORs (95% CI) of MetS prevalence across the quartile of urinary 2,5-dichlorophenol (2,5-DCP) were 1.09 (0.93-1.28), 1.22 (1.00-1.49), and 1.34 (1.04-1.73). Moreover, 2,5 DCP is significantly associated with a higher prevalence of abdominal obesity [ORQ4vsQ1 (95% CI): 1.23 (1.03-1.48)]. The WQS and qgcomp index also showed significant associations between p-DCB metabolites and MetS. Moreover, we further examined that 2,5 DCP was correlated with higher systolic blood pressure (r = 0.022, P = 0.027), waist circumference (r = 0.099, P < 0.001), and glycohemoglobin (r = 0.027, P = 0.008) and a lower high density cholesterol (r = -0.059, P < 0.001). In addition, the significant positive associations between 2,5 DCP and MetS were robust in the subgroup and sensitivity analyses.

Conclusion

These findings indicated that increased urinary p-DCB concentration, especially 2,5 DCP, had a higher MetS prevalence. These results should be interpreted cautiously and further research is warranted to validate our findings.
Neuronal-specific TNFAIP1 ablation attenuates postoperative cognitive dysfunction via targeting SNAP25 for K48-linked ubiquitination
Authors: Wang Wei , Gao Wenwei , Gong Ping , Song Wenqin , Bu Xueshan , Hou Jiabao , Zhang Lei , Zhao Bo
Published: December 2023

Background

Synaptosomal-associated protein 25 (SNAP25) exerts protective effects against postoperative cognitive dysfunction (POCD) by promoting PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy and repressing caspase-3/gasdermin E (GSDME)-mediated pyroptosis. However, the regulatory mechanisms of SNAP25 protein remain unclear.

Methods

We employed recombinant adeno-associated virus 9 (AAV9)-hSyn to knockdown tumor necrosis factor α-induced protein 1 (TNFAIP1) or SNAP25 and investigate the role of TNFAIP1 in POCD. Cognitive performance, hippocampal injury, mitophagy, and pyroptosis were assessed. Co-immunoprecipitation (co-IP) and ubiquitination assays were conducted to elucidate the mechanisms by which TNFAIP1 stabilizes SNAP25.

Results

Our results demonstrated that the ubiquitin ligase TNFAIP1 was upregulated in the hippocampus of mice following isoflurane (Iso) anesthesia and laparotomy. The N-terminal region (residues 1–96) of TNFAIP1 formed a conjugate with SNAP25, leading to lysine (K) 48-linked polyubiquitination of SNAP25 at K69. Silencing TNFAIP1 enhanced SH-SY5Y cell viability and conferred antioxidant, pro-mitophagy, and anti-pyroptosis properties in response to Iso and lipopolysaccharide (LPS) challenges. Conversely, TNFAIP1 overexpression reduced HT22 cell viability, increased reactive oxygen species (ROS) accumulation, impaired PINK1/Parkin-dependent mitophagy, and induced caspase-3/GSDME-dependent pyroptosis by suppressing SNAP25 expression. Neuron-specific knockdown of TNFAIP1 ameliorated POCD, restored mitophagy, and reduced pyroptosis, which was reversed by SNAP25 depletion.

Conclusions

In summary, our findings demonstrated that inhibiting TNFAIP1-mediated degradation of SNAP25 might be a promising therapeutic approach for mitigating postoperative cognitive decline.
3D MR fingerprinting-derived myelin water fraction characterizing brain development and leukodystrophy
Authors: Kim Hyun Gi , Han Dongyeob , Kim Jimin , Choi Jeong-Sun , Cho Kyung-Ok
Published: December 2023

Background

Magnetic resonance fingerprinting (MRF) enables fast myelin quantification via the myelin water fraction (MWF), offering a noninvasive method to assess brain development and disease. However, MRF-derived MWF lacks histological evaluation and remains unexamined in relation to leukodystrophy. This study aimed to access MRF-derived MWF through histology in mice and establish links between myelin, development, and leukodystrophy in mice and children, demonstrating its potential applicability in animal and human studies.

Methods

3D MRF was performed on normal C57BL/6 mice with different ages, megalencephalic leukoencephalopathy with subcortical cyst 1 wild type (MLC1 WT, control) mice, and MLC 1 knock-out (MLC1 KO, leukodystrophy) mice using a 3 T MRI. MWF values were analyzed from 3D MRF data, and histological myelin quantification was carried out using immunohistochemistry to anti-proteolipid protein (PLP) in the corpus callosum and cortex. The associations between ‘MWF and PLP’ and ‘MWF and age’ were evaluated in C57BL/6 mice. MWF values were compared between MLC1 WT and MLC1 KO mice. MWF of normal developing children were retrospectively collected and the association between MWF and age was assessed.

Results

In 35 C57BL/6 mice (age range; 3 weeks–48 weeks), MWF showed positive relations with PLP immunoreactivity in the corpus callosum (β = 0.0006, P = 0.04) and cortex (β = 0.0005, P = 0.006). In 12-week-old C57BL/6 mice MWF showed positive relations with PLP immunoreactivity (β = 0.0009, P = 0.003, R2 = 0.54). MWF in the corpus callosum (β = 0.0022, P < 0.001) and cortex (β = 0.0010, P < 0.001) showed positive relations with age. Seven MLC1 WT and 9 MLC1 KO mice showed different MWF values in the corpus callous (P < 0.001) and cortex (P < 0.001). A total of 81 children (median age, 126 months; range, 0–199 months) were evaluated and their MWF values according to age showed the best fit for the third-order regression model (adjusted R2 range, 0.44–0.94, P < 0.001).

Conclusion

MWF demonstrated associations with histologic myelin quantity, age, and the presence of leukodystrophy, underscoring the potential of 3D MRF-derived MWF as a rapid and noninvasive quantitative indicator of brain myelin content in both mice and humans.
CSF-1R inhibitor PLX3397 attenuates peripheral and brain chronic GVHD and improves functional outcomes in mice
Authors: Shaikh Samreen N. , Willis Emily F. , Dierich Max , Xu Yi , Stuart Samuel J. S. , Gobe Glenda C. , Bashaw Abate A. , Rawashdeh Oliver , Kim Seung Jae , Vukovic Jana
Published: December 2023

Graft-versus-host disease (GVHD) is a serious complication of otherwise curative allogeneic haematopoietic stem cell transplants. Chronic GVHD induces pathological changes in peripheral organs as well as the brain and is a frequent cause of late morbidity and death after bone-marrow transplantation. In the periphery, bone-marrow-derived macrophages are key drivers of pathology, but recent evidence suggests that these cells also infiltrate into cGVHD-affected brains. Microglia are also persistently activated in the cGVHD-affected brain. To understand the involvement of these myeloid cell populations in the development and/or progression of cGVHD pathology, we here utilized the blood–brain-barrier permeable colony stimulating factor-1 receptor (CSF-1R) inhibitor PLX3397 (pexidartinib) at varying doses to pharmacologically deplete both cell types. We demonstrate that PLX3397 treatment during the development of cGVHD (i.e., 30 days post-transplant) improves disease symptoms, reducing both the clinical scores and histopathology of multiple cGVHD target organs, including the sequestration of T cells in cGVHD-affected skin tissue. Cognitive impairments associated with cGVHD and neuroinflammation were also attenuated by PLX3397 treatment. PLX3397 treatment prior to the onset of cGVHD (i.e., immediately post-transplant) did not change in clinical scores or histopathology. Overall, our data demonstrate significant benefits of using PLX3397 for the treatment of cGVHD and associated organ pathologies in both the periphery and brain, highlighting the therapeutic potential of pexidartinib for this condition.
Determinants of survival of adolescents receiving antiretroviral therapy in the Centre Region of Cameroon: a multi-centered cohort-analysis
Authors: Tendongfor Nicholas , Fokam Joseph , Chenwi Collins Ambe , Nwabo Fabrice Léo Tamhouo , Nangmo Armanda , Debimeh Njume , Moyo Suzie Tetang Ndiang , Halle Marie Patrice , Njom-Nlend Anne-Esther , Ndombo Paul Koki , Ndjolo Alexis
Published: December 2023

Background

In spite of the global decreasing mortality associated with HIV, adolescents living with HIV (ADLHIV) in sub-Saharan Africa still experience about 50% mortality rate. We sought to evaluate survival rates and determinants of mortality amongst ADLHIV receiving antiretroviral therapy (ART) in urban and rural settings.

Methods

A multi-centered, 10-year retrospective, cohort-study including ADLHIV on ART ≥ 6 months in the urban and rural settings of the Centre Region of Cameroon. Socio-demographic, clinical, biological, and therapeutic data were collected from files of ADLHIV. The Kaplan–Meier method was used to estimate survival probability after ART initiation; the log rank test used to compare survival curves between groups of variables; and the Cox proportional hazard model was used to identify the determinants of mortality.

Results

A total of 403 adolescents’ records were retained; 340 (84%) were from the urban and 63 (16%) from the rural settings. The female to male ratio was 7:5; mean age (Standard deviation) was 14.1 (2.6) years; at baseline, 64.4% were at WHO clinical stages I/II, 34.9% had ≥ 500 CD4 cells/mm3, 91.1% were anemic, and the median [Inter Quartile Range] duration on ART was5.3 [0.5–16] years. The survival rate at 1, 5 and 10 years on ART was respectively 97.0%, 55.9% and 8.7%; with mean survival time of 5.8 years (95% CI 5.5–6.1). In bivariate analysis, living in the rural setting, non-disclosed HIV status, baseline CD4 count < 500 cells/mm3, not being exposed to nevirapine prophylaxis at birth and being horizontally infected were found to be the determinants of higher mortality with poor retention in care slightly associated with mortality. In multivariate analysis, living in rural settings, poor retention in care and anemia were independent predictors of mortality (p < 0.05).

Conclusion

Although ADLHIV have good survival rate on ART after 1 year, we observe poor survival rates after 5 years and especially 10 years of treatment experience. Mitigating measures against poor survival should target those living in rural settings, anemic at baseline, or experiencing poor retention in care.