bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping three-dimensional intratumor proteomic heterogeneity in uterine serous carcinoma by multiregion microsampling
Authors: Hunt Allison L. , Bateman Nicholas W. , Barakat Waleed , Makohon-Moore Sasha C. , Abulez Tamara , Driscoll Jordan A. , Schaaf Joshua P. , Hood Brian L. , Conrads Kelly A. , Zhou Ming , Calvert Valerie , Pierobon Mariaelena , Loffredo Jeremy , Wilson Katlin N. , Litzi Tracy J. , Teng Pang-Ning , Oliver Julie , Mitchell Dave , Gist Glenn , Rojas Christine , Blanton Brian , Darcy Kathleen M. , Rao Uma N. M. , Petricoin Emanuel F. , Phippen Neil T. , Maxwell G. Larry , Conrads Thomas P.
Published: January 2024

Background

Although uterine serous carcinoma (USC) represents a small proportion of all uterine cancer cases, patients with this aggressive subtype typically have high rates of chemotherapy resistance and disease recurrence that collectively result in a disproportionately high death rate. The goal of this study was to provide a deeper view of the tumor microenvironment of this poorly characterized uterine cancer variant through multi-region microsampling and quantitative proteomics.

Methods

Tumor epithelium, tumor-involved stroma, and whole “bulk” tissue were harvested by laser microdissection (LMD) from spatially resolved levels from nine USC patient tumor specimens and underwent proteomic analysis by mass spectrometry and reverse phase protein arrays, as well as transcriptomic analysis by RNA-sequencing for one patient’s tumor.

Results

LMD enriched cell subpopulations demonstrated varying degrees of relatedness, indicating substantial intratumor heterogeneity emphasizing the necessity for enrichment of cellular subpopulations prior to molecular analysis. Known prognostic biomarkers were quantified with stable levels in both LMD enriched tumor and stroma, which were shown to be highly variable in bulk tissue. These USC data were further used in a comparative analysis with a data generated from another serous gynecologic malignancy, high grade serous ovarian carcinoma, and have been added to our publicly available data analysis tool, the Heterogeneity Analysis Portal (https://lmdomics.org/).

Conclusions

Here we identified extensive three-dimensional heterogeneity within the USC tumor microenvironment, with disease-relevant biomarkers present in both the tumor and the stroma. These data underscore the critical need for upfront enrichment of cellular subpopulations from tissue specimens for spatial proteogenomic analysis.
A Mitochondrial Localized Chaperone Regulator OsBAG6 Functions in Saline-Alkaline Stress Tolerance in Rice
Authors: Wang Jie , Ao Min , Ma Ao , Yu Jinlei , Guo Peng , Huang Shuangzhan , Peng Xiaoyuan , Yun Dae-Jin , Xu Zheng-Yi
Published: January 2024

B-cell lymphoma 2 (Bcl-2)-associated athanogene (BAG) family genes play prominent roles in regulating plant growth, development, and stress response. Although the molecular mechanism underlying BAG’s response to abiotic stress has been studied in Arabidopsis, the function of OsBAG underlying saline-alkaline stress tolerance in rice remains unclear. In this study, OsBAG6, a chaperone regulator localized to mitochondria, was identified as a novel negative regulator of saline-alkaline stress tolerance in rice. The expression level of OsBAG6 was induced by high concentration of salt, high pH, heat and abscisic acid treatments. Overexpression of OsBAG6 in rice resulted in significantly reduced plant heights, grain size, grain weight, as well as higher sensitivity to saline-alkaline stress. By contrast, the osbag6 loss-of-function mutants exhibited decreased sensitivity to saline-alkaline stress. The transcriptomic analysis uncovered differentially expressed genes related to the function of “response to oxidative stress”, “defense response”, and “secondary metabolite biosynthetic process” in the shoots and roots of OsBAG6-overexpressing transgenic lines. Furthermore, cytoplasmic levels of Ca2+ increase rapidly in plants exposed to saline-alkaline stress. OsBAG6 bound to calcium sensor OsCaM1-1 under normal conditions, which was identified by comparative interactomics, but not in the presence of elevated Ca2+. Released OsCaM1-1 saturated with Ca2+ is then able to regulate downstream stress-responsive genes as part of the response to saline-alkaline stress. OsBAG6 also interacted with energy biosynthesis and metabolic pathway proteins that are involved in plant growth and saline-alkaline stress response mechanisms. This study reveals a novel function for mitochondrial localized OsBAG6 proteins in the saline-alkaline stress response alongside OsCaM1-1.
Exposure to heavy metals and neurocognitive function in adults: a systematic review
Authors: Althomali Raed H. , Abbood Manal A. , Saleh Ebraheem Abdu Musad , Djuraeva Laylo , Abdullaeva Barno Sayfutdinovna , Habash Ruqayah Taher , Alhassan Muataz S. , Alawady Ahmed Hussien Radie , Alsaalamy Ali Hashiem , Najafi Moslem Lari
Published: January 2024

Exposure of individuals to heavy metals (HMs) is a growing concern with far-reaching implications for human health. HMs encompass a diverse range of elements that, when present in excess or in particular chemical forms, have the potential to elicit adverse effects on the central nervous system and cognitive function. This systematic review aims to comprehensively investigate the relationship between exposure to HMs and neurocognitive function in adults. The methodological framework for this review adheres rigorously to the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines. A meticulous and extensive search strategy was executed within PubMed and Web of Science, specifically targeting articles published in the English language until the cutoff date of December 5, 2023. The evaluation of the retrieved studies was systematically conducted by employing the assessment approach outlined by (Gascon et al. in Environ Int 86 60 67, 2016). The initial search yielded a substantial pool of 1573 articles, culminating in a refined selection comprising eight pertinent studies, collectively enrolling a participant cohort totalling n = 1,828,126. Notably, the studies under review predominantly manifested a cross-sectional or cohort design and were geographically situated within the continents of North America and Asia. Furthermore, it is imperative to underscore that a predominant and recurring observation emanating from the majority of the scrutinized investigations underscores a significant correlation between exposure to cadmium (Cd) and mercury (Hg) and deleterious neurocognitive outcomes in the adult population. In summary, our systematic review postulates that exposure to HMs through various routes of exposure harbors the potential for adverse effects on adult neurocognitive function; however, it is incumbent upon future research endeavors to validate and corroborate these findings through further empirical exploration.
Genome characteristics and the ODV proteome of a second distinct alphabaculovirus from Spodoptera litura
Authors: Gao Weisong , Liu Xingjian , Gao Xintao , Wu Tong , Wei Shuang , Zhang Zhifang , Zhang Huan , Li Yinü
Published: January 2024

Background

Spodoptera litura is a harmful pest that feeds on more than 80 species of plants, and can be infected and killed by Spodoptera litura nucleopolyhedrovirus (SpltNPV). SpltNPV-C3 is a type C SpltNPV clone, that was observed and collected in Japan. Compared with type A or type B SpltNPVs, SpltNPV-C3 can cause the rapid mortality of S. litura larvae.

Methods

In this study, occlusion bodies (OBs) and occlusion-derived viruses (ODVs) of SpltNPV-C3 were purified, and OBs were observed by scanning electron microscopy (SEM). ODVs were observed under a transmission electron microscope (TEM).

Results

Both OBs and ODVs exhibit morphological characteristics typical of nucleopolyhedroviruses (NPVs).The genome of SpltNPV-C3 was sequenced and analyzed; the total length was 148,634 bp (GenBank accession 780,426,which was submitted as SpltNPV-II), with a G + C content of 45%. A total of 149 predicted ORFs were found. A phylogenetic tree of 90 baculoviruses was constructed based on core baculovirus genes. LC‒MS/MS was used to analyze the proteins of SpltNPV-C3; 34 proteins were found in the purified ODVs, 15 of which were core proteins. The structure of the complexes formed by per os infectivity factors 1, 2, 3 and 4 (PIF-1, PIF-2, PIF-3 and PIF-4) was predicted with the help of the AlphaFold multimer tool and predicted conserved sequences in PIF-3. SpltNPV-C3 is a valuable species because of its virulence, and the analysis of its genome and proteins in this research will be beneficial for pest control efforts.
Ultrasonic optic nerve sheath diameter can be used as a diagnostic measure after accidental dural puncture during cesarean section: a case report
Authors: Wang Pei , Zhou Xia , Sheng Fang , Wang Xiaolong , Shi Caifeng , Feng Wei
Published: January 2024

Background

Parturients are prone to postdural puncture headache (PDPH) after epidural puncture. Cerebral venous sinus thrombosis (CVST) is a fatal complication of PDPH. The main symptom of both is headache, however, the mechanism is not similar. For persistent PDPH, early differential diagnosis from CVST is essential. Optic nerve sheath diameter (ONSD) measurements can be used to identify changes in intracranial pressure as an auxiliary tool to distinguish the cause of headache.

Case presentation

The dura of a 32-year-old woman undergoing cesarean section was accidentally penetrated while administering epidural anesthesia, and the patient developed PDPH the subsequent day. The patient refused epidural blood patch (EBP) treatment and was discharged after conservative treatment. Fourteen days post-discharge, she was readmitted for a seizure. Magnetic resonance imaging (MRI) and Magnetic resonance angiography (MRA) indicated low cranial pressure syndrome and superior sagittal sinus thrombosis with acute infarction. The next morning, the EBP was performed with 15 ml autologous blood. Subsequently, the headache symptoms decreased during the day and worsened at night. ONSD measurement suggested dilation of the optic nerve sheath, and subsequently, the patient showed intracranial hypertension with papilledema. After dehydration and anticoagulant treatment, the patient’s symptoms were relieved and she was discharged from the hospital 49 days later.

Conclusions

Headache is the main symptom of PDPH and cerebral venous thrombosis, which are difficult to distinguish. ONSD measurement may help to estimate the intracranial pressure, and early measurement may be helpful for women with PDPH to avoid serious complications, such as CVST.
Understanding facilitators of research participation among adults with self-reported chronic pain – a survey examining hypothetical research participation
Authors: Start Charles , McBride Meagan , Zhu Guohao , Shaikh Sana , Pierce Jennifer
Published: January 2024

Background

An inability to successfully recruit participants into clinical research has consequences that negatively affect the conduct and reliability of research studies. Understanding facilitators of research participation, namely motives for participation and preferred research outcomes, may improve recruitment and retention of clinical trials related to chronic pain. The present study explored research participation facilitators among individuals with chronic pain and their association with demographic characteristics, pain-related characteristics, and factors related to future research engagement.

Methods

Individuals from Michigan who were 18 years or older and self-reported having chronic pain completed an online survey assessing motives for research participation and desired research outcomes. Analyses were conducted in three stages. First, we evaluated underlying factors of motives for participation and research outcome preferences using principal components analysis. Second, we classified individuals according to their patterns of facilitators using latent profile analysis. Finally, we evaluated differences between facilitator profiles in demographic characteristics, pain-related characteristics, and factors related to future research engagement using χ2 analyses and Kruskal-Wallis rank sum tests.

Results

Three components of motives for research participation were identified: social engagement/enjoyment; pain improvement/advancing science; and compensation. Three components of research outcome preferences were identified: co-occurring symptom reduction; behavior reduction modification; and pain and function improvement. Four potential patient-centered profiles utilizing these dimensions of facilitators were identified that had unique demographic characteristics, research participation willingness, and treatment interest.

Conclusions

Our data provide a framework of motives and research outcome preferences that may inform recruitment and retention in chronic pain research. It also gives an indication of who may respond best to active or passive recruitment strategies that appeal to a given motive or preferred outcome. This information may be useful for improving recruitment and to monitor any potential biases in participant samples.
A case of unexpected diagnosis of fibronectin glomerulopathy with histological features of membranoproliferative glomerulonephritis
Authors: Hata Misa , Mori Takayasu , Hirose Yurika , Nishida Yuriko , Mandai Shintaro , Ando Fumiaki , Susa Koichiro , Iimori Soichiro , Naito Shotaro , Sohara Eisei , Rai Tatemitsu , Taguchi Towako , Tomii Shohei , Ohashi Kenichi , Uchida Shinichi
Published: January 2024

Fibronectin (FN) glomerulopathy (FNG), a rare autosomal hereditary renal disease, is characterized by proteinuria resulting from the massive accumulation of FN in the glomeruli. It typically affects individuals aged 10–50 years. In this report, we describe the case of a 57-year-old man who was diagnosed with FNG through genetic analysis and histological examination that revealed membranoproliferative glomerulonephritis. Despite treatment with prednisolone, the therapeutic response was unsatisfactory. Prednisolone was subsequently tapered and discontinued because the patient had pulmonary thromboembolism. Subsequent comprehensive genetic testing, which was initially not conducted because the patient’s parents did not have a history of kidney disease, identified a known disease-causing variant in the FN1 gene, indicating a de novo variant. FNG was further confirmed by positive staining of glomeruli with FN using an IST-4 antibody. Although corticosteroid therapy is commonly employed as the initial treatment for MPGN, its appropriateness depends on the underlying etiology. Thus, clinicians must be aware of potential rare genetic causes underlying MPGN.
Does visuospatial neglect contribute to standing balance within the first 12 weeks post-stroke? A prospective longitudinal cohort study
Authors: Embrechts Elissa , Schröder Jonas , Nijboer Tanja C. W. , van der Waal Charlotte , Lafosse Christophe , Truijen Steven , Saeys Wim
Published: January 2024

Background

Visuospatial neglect (VSN) has been suggested to limit standing balance improvement post-stroke. However, studies investigating this association longitudinally by means of repeated within-subject measurements early post-stroke are lacking. This prospective longitudinal cohort study evaluates the longitudinal association of egocentric and allocentric VSN severity with 1) standing balance independence and 2) postural control and weight-bearing asymmetry (WBA) during quiet standing, in the first 12 weeks post-stroke.

Methods

Thirty-six hemiplegic individuals after a first-ever unilateral stroke were evaluated at weeks 3, 5, 8 and 12 post-stroke. Egocentric and allocentric VSN severity were evaluated using the Broken Hearts Test. The standing unperturbed item of the Berg Balance Scale (BBS-s) was used to clinically evaluate standing independence. Posturographic measures included measures of postural control (mediolateral (ML)/anteroposterior (AP) net center-of-pressure velocities (COPvel)) and WBA during quiet standing. A linear mixed model was used to examine longitudinal associations between egocentric and allocentric VSN, and BBS-s, COPvel-ML, COPvel-APand WBA within the first 12 weeks post-stroke.

Results

Egocentric (β = -0.08, 95%CI[-0.15;-0.01],P = .029) and allocentric VSN severity (β = -0.09, 95%CI[-0.15; -0.04],P = .002) were significant independent factors for BBS-s scores in the first 12 weeks post-stroke. Egocentric and allocentric VSN were no significant independent factors for COPvel-ML, COPvel-APand WBA in the first 12 weeks post-stroke.

Conclusions

Allocentric and egocentric VSN severity were significantly associated with decreased standing independence, but not impaired postural control or greater asymmetric weight-bearing, in the early subacute post-stroke phase. This may involve traditional VSN measures being not sensitive enough to detect fine-grained VSN deficits due to a ceiling effect between 5 and 8 weeks post-stroke, once the individual regains standing ability. Future studies may require more sensitive VSN measurements to detect such deficits.

Trial registration

Clinicaltrials.gov. unique identifier NCT05060458.
Cancer-associated fibroblast-derived extracellular vesicles promote lymph node metastases in oral cavity squamous cell carcinoma by encapsulating ITGB1 and BMI1
Authors: Lv Tianzhu , Liu Hongjing , Mao Ling , Song Yanrong , Liao Lili , Zhong Kun , Shuai Binbin , Luo Yingkun , Guo Tingting , Huang Wentao , Zhang Shenyingjie
Published: January 2024

Background

Extracellular vesicles (EVs) have been revealed to facilitate the development of oral squamous cavity cell carcinoma (OCSCC), while its supporting role in lymph node metastases is under continuous investigation. This study aimed to examine the function of cancer-associated fibroblasts (CAF)-derived EVs (CAF-EVs) during lymph node metastasis in OCSCC and the mechanisms.

Methods

CAF were isolated from OCSCC tissues of patients, and CAF-EVs were extracted and identified. EdU, colony formation, wound healing, and Transwell assays were performed. The OCSCC cells before and after CAF-EVs treatment were injected into mice to probe the effects of CAF-EVs on tumor growth and lymph node metastasis, respectively. The effect of CAF-EVs treatment on transcriptome changes in OCSCC cells was analyzed. Clinical data of patients with OCSCC were analyzed to determine the prognostic significance of the selected genes. Finally, loss-of-function assays were conducted to corroborate the involvement of polycomb complex protein BMI-1 (BMI1) and integrin beta1 (ITGB1).

Results

CAF-EVs promoted the malignant behavior of OCSCC cells and accelerated tumor growth and lymph node metastasis in mice. CAF-EVs significantly increased the expression of BMI1 and ITGB1, and the expression of BMI1 and ITGB1 was negatively correlated with the overall survival and relapse-free survival of OCSCC patients. Knockdown of BMI1 or ITGB1 in OCSCC cells abated the promoting effects of CAF-EVs in vitro and in vivo.

Conclusion

CAF-EVs elicited the metastasis-promoting properties in OCSCC by elevating BMI1 and ITGB1, suggesting that BMI1 and ITGB1 could be potential biomarkers and therapeutic targets for OCSCC.
Evaluation of psychological distress, burnout and structural empowerment status of healthcare workers during the outbreak of coronavirus disease (COVID-19): a cross-sectional questionnaire-based study
Authors: Taleb Sara , Vahedian-Azimi Amir , Karimi Leila , Salim Safa , Mohammad Farhan , Samhadaneh Dana , Singh Kalpana , Hussein Nur-Run , Ait Hssain Ali
Published: January 2024

Background

In light of several recent studies, there is evidence that the coronavirus disease 2019 (COVID-19) pandemic has caused various mental health concerns in the general population, as well as among healthcare workers (HCWs). The main aim of this study was to assess the psychological distress, burnout and structural empowerment status of HCWs during the COVID-19 outbreak, and to evaluate its predictors.

Methods

This multi-center, cross-sectional web-based questionnaire survey was conducted on HCWs during the outbreak of COVID-19 from August 2020 to January 2021. HCWs working in hospitals from 48 different countries were invited to participate in an online anonymous survey that investigated sociodemographic data, psychological distress, burnout and structural empowerment (SE) based on Depression Anxiety and Stress Scale 21 (DASS-21), Maslach Burnout Inventory (MBI) and Conditions for work effectiveness questionnaire (CWEQ_II), respectively. Predictors of the total scores of DASS-21, MBI and CWEQ-II were assessed using unadjusted and adjusted binary logistic regression analysis.

Results

Out of the 1030 HCWs enrolled in this survey, all completed the sociodemographic section (response rate 100%) A total of 730 (70.9%) HCWs completed the DASS-21 questionnaire, 852 (82.6%) completed the MBI questionnaire, and 712 (69.1%) completed the CWEQ-II questionnaire. The results indicate that 360 out of 730 responders (49.3%) reported severe or extremely severe levels of stress, anxiety, and depression. Additionally, 422 out of 851 responders (49.6%) reported a high level of burnout, while 268 out of 712 responders (37.6%) reported a high level of structural empowerment based on the DASS-21, MBI, and CWEQ-II scales, respectively. In addition, the analysis showed that HCWs working in the COVID-19 areas experienced significantly higher symptoms of severe stress, anxiety, depression and higher levels of burnout compared to those working in other areas. The results also revealed that direct work with COVID-19 patients, lower work experience, and high workload during the outbreak of COVID-19 increase the risks of negative psychological consequences.

Conclusion

Health professionals had high levels of burnout and psychological symptoms during the COVID-19 emergency. Monitoring and timely treatment of these conditions is needed.
Decomposing the rural–urban differences in depression among multimorbid older patients in India: evidence from a cross-sectional study
Authors: Saha Amiya , Mandal Bittu , Muhammad T. , Ali Waad
Published: January 2024

Background

In India, the prevalence of depression among older adults dealing with multiple health conditions varies between rural and urban areas due to disparities in healthcare access and cultural factors. The distinct patterns observed underscore the necessity for tailored research and interventions to address mental health inequalities among multimorbid older patients in diverse geographic contexts.

Methods

This study used data from the Longitudinal Ageing Study in India (LASI) wave 1 (2017–18). A total of 7,608 adults aged ≥ 60 years who were diagnosed with two or more chronic conditions (such as hypertension, diabetes, cancer, chronic lung disease, chronic heart diseases, stroke, bone/joint disease, any neurological or psychiatric diseases, and high cholesterol) were included in this study. Descriptive statistics, bivariate analysis, logistic regression estimates, and Fairlie decomposition method were used to accomplish the study’s objectives.

Results

The prevalence of depression among older adults with multimorbidity was 9.48% higher in rural areas (38.33%) than in urban areas (28.85%).. Older adults with multimorbidity belonging to the scheduled caste group were 40% more likely to experience depression. Moreover, those with multimorbidity and any form of disability in activities of daily living (ADL) were 93% more likely to experience depression than those without disability, whereas those with multimorbidity and perceived good general health were 65% less likely to suffer from depression than those with poor self-perceived health. Additionally, decomposition analysis revealed that education (35.99%), caste status (10.30%), IADL disability (19.30%), and perceived discrimination (24.25%) were the primary factors contributing to the differences in depression prevalence among older adults with multimorbidity between rural and urban areas.

Conclusions

We found significant rural–urban differences in depression among older Indians with multimorbidity. The findings underscore the need for targeted interventions that address the unique challenges faced by older patients in rural areas, including lack of social capital, discrimination, and limited resources that enable access to healthcare services. Policymakers and healthcare professionals must collaboratively design and implement effective strategies to improve the mental health and overall well-being of rural older adults, particularly those with multiple comorbidities.
Adolescent alcohol and cannabis use and early adulthood educational attainment in the 1986 Northern Finland birth cohort study
Authors: Levola Jonna , Alakokkare Anni-Emilia , Denissoff Alexander , Mustonen Antti , Miettunen Jouko , Niemelä Solja
Published: January 2024

Background

Heavy alcohol and cannabis use during adolescence have been previously described as risk factors not only for morbidity in adulthood, but also social problems including adversities in educational attainment. Attempts to consider overlapping risk factors and confounders for these associations are needed.

Methods

Using weighted multivariable models, we examined prospective associations between age at first drink (AFD), age at first intoxication (AFI), frequency of alcohol intoxication, as well as self-reported alcohol tolerance (i.e., number of drinks needed for the subjective experience of intoxication), and lifetime cannabis use at age 15/16 years with subsequent educational attainment obtained from comprehensive registers until age 33 in the Northern Finland Birth Cohort 1986 (6,564 individuals, 49.1% male). Confounding variables including sex, family structure (intact vs. non-intact), maternal and paternal education level, behavioural/emotional problems in school at age 7/8 years, having a history of illicit substance use in adolescence, having any psychiatric diagnosis before age 16, and parental psychiatric diagnoses, were adjusted for.

Results

In this large birth cohort study with a 17-year follow-up, younger age at first intoxication, higher frequency of alcohol intoxication, and high self-reported alcohol tolerance at age 15/16 years were associated with poorer educational outcomes by the age of 33 years. These associations were evident regardless of potential confounders, including parental education and childhood behavioural/emotional problems. The association between adolescent cannabis use and educational attainment in adulthood was no longer statistically significant after adjusting for confounders including frequency of alcohol intoxication at age 15/16.

Conclusions

Assessments of age of first alcohol intoxication, high self-reported alcohol tolerance and frequency of intoxication during adolescence should be included when implementing screening strategies aimed at identifying adolescents at risk for subsequent social problems.
Association between screen time and physical activity on mental health among preschoolers: a cross-sectional study from Southwest China
Authors: Liang Yi , Jin Qiyun , Miao Junjie , Ni Xiaorong , Qian Xiaoxiao , Xiong Yi , Liu Zhijun , Xue Hongmei
Published: January 2024

Background

Screen time and physical activity behaviors undergo development during early childhood and impact mental health. However, there is limited knowledge regarding the associations between physical activity, screen time, and mental health problems (MHP) in preschoolers. This study examines these associations using a large sample size and brief measures.

Methods

A multistage cluster stratified sampling method was used to conduct an observational cross-sectional study of 19,015 Chinese preschoolers in 2020. Information on physical activity, and screen time was collected by a self-administered questionnaire; MHP was assessed by the parent-reported Strengths and Difficulties Questionnaire (SDQ). Logistic regression models were used to obtain the odds ratios (ORs) and 95% confidence intervals (95% CIs) of preschoolers’ MHP associated with screen time, total physical activities, moderate to vigorous physical activity (MVPA), and outdoor physical activities.

Results

A total of 19,015 participants from the 19,548 recruited population were included in the analyses (missing rate: 2.73%), 52.60% were boys. 64.01%, 57.96%, 35.98%, and 82.64% of preschoolers were reported to meet total physical activities, MVPA, and outdoor activities with screen time recommendations level. The results of multivariable-adjusted ORs (95% CIs) of preschoolers’ MHP for comparisons of different levels of screen time (< 2 h/day, 2–4 h/day,≥4 h/day) show that screen time positively associated with MHP after adjusting for confounders (P < 0.05), but the association was not significant among girls with screen time ≥ 4 h/day. In addition, increased engagement in physical activity was reversely linked to MHP (P < 0.05). A stronger association between MHP and MVPA was observed in boys, however, this association was weakened when the total time spent engaging in MVPA exceeded two hours per day (P < 0.05).

Conclusion

Less physical activity and more screen time positively relate to MHP, but the relationship differs by type of physical activity, total time, and gender. These findings provide novel insights and evidence supporting for guidelines on physical activity, screen time, and improvement of mental health for preschoolers.
Is health literacy of adolescent athletes’ parents whose children belonged to sports clubs related to their children’s intention to receive medications, vaccines, supplements, and energy drinks? A cross-sectional study
Authors: Nakajima Rie , Komoriya Michihiro , Watanabe Fumiyuki
Published: January 2024

Background

Adolescent athletes’ values ​regarding health behaviors, including their attitudes toward doping, are largely derived from those of their parents. Therefore, clarifying the factors that affect parents’ intentions regarding their children’s medicine intake and nutrition can help elucidate the process of forming values ​​of healthy behaviors in young athletes.

Methods

Between March 8 and March 9, 2021, an online questionnaire survey was conducted via an Internet research company; data from 2,000 residents in Japan were collected. Participants were male and female residents aged 30–59 years with children in elementary or high school and belonging to sports clubs. The survey items included respondent’s and child’s basic information, respondent’s health literacy, and level of sports in which the respondent and child were (or are) engaged. Respondents were also asked if they would like their children to receive prescription drugs, over-the-counter drugs, herbal medicines, vaccines, supplements, or energy drinks. Logistic regression analysis was performed to analyze the relationship between respondents’ basic information and health literacy and their intention to receive prescription and over-the-counter drugs, herbal medicines, vaccines, supplements, and energy drinks.

Results

Higher parental health literacy was associated with higher children’s willingness to receive prescription drugs (odds ratio [OR] = 1.025, 95% confidence interval [CI]: 1.016–1.035), over-the-counter drugs (OR = 1.012, 95% CI: 1.003–1.021), prescription herbal medicines (OR = 1.021, 95% CI: 1.021–1.030), over-the-counter herbal medicines (OR = 1.012, 95% CI: 1.003–1.021), and vaccines (OR = 1.025, 95% CI: 1.016–1.035). Conversely, the children’s intention to receive energy drinks (OR = 0.990, 95% CI: 0.980–1.000) decreased significantly. As the child’s athletic level increased, parents’ willingness for their children to receive oral prescription medicines decreased (OR = 0.886, 95% CI: 0.791–0.992) and that to receive supplements (OR = 1.492, 95% CI: 1.330–1.673) and energy drinks significantly increased (OR = 1.480, 95% CI: 1.307–1.676).

Conclusion

Health literacy of adolescent athletes’ parents is associated with their children’s willingness to receive medicines. Healthcare providers should counsel parents of adolescent athletes to allow their children to receive necessary drug treatments and prevent doping violations caused by supplement intake.
Anti-rheumatic colchicine phytochemical exhibits potent antiviral activities against avian and seasonal Influenza A viruses (IAVs) via targeting different stages of IAV replication cycle
Authors: Hegazy Akram , Soltane Raya , Alasiri Ahlam , Mostafa Islam , Metwaly Ahmed M. , Eissa Ibrahim H. , Mahmoud Sara H. , Allayeh Abdou Kamal , Shama Noura M. Abo , Khalil Ahmed A. , Barre Ramya S. , El-Shazly Assem Mohamed , Ali Mohamed A. , Martinez-Sobrido Luis , Mostafa Ahmed
Published: January 2024

Background

The continuous evolution of drug-resistant influenza viruses highlights the necessity for repurposing naturally-derived and safe phytochemicals with anti-influenza activity as novel broad-spectrum anti-influenza medications.

Methods

In this study, nitrogenous alkaloids were tested for their viral inhibitory activity against influenza A/H1N1 and A/H5N1 viruses. The cytotoxicity of tested alkaloids on MDCK showed a high safety range (CC50 > 200 µg/ml), permitting the screening for their anti-influenza potential.

Results

Herein, atropine sulphate, pilocarpine hydrochloride and colchicine displayed anti-H5N1 activities with IC50 values of 2.300, 0.210 and 0.111 µg/ml, respectively. Validation of the IC50 values was further depicted by testing the three highly effective alkaloids, based on their potent IC50 values against seasonal influenza A/H1N1 virus, showing comparable IC50 values of 0.204, 0.637 and 0.326 µg/ml, respectively. Further investigation suggests that colchicine could suppress viral infection by primarily interfering with IAV replication and inhibiting viral adsorption, while atropine sulphate and pilocarpine hydrochloride could directly affect the virus in a cell-free virucidal effect. Interestingly, the in silico molecular docking studies suggest the abilities of atropine, pilocarpine, and colchicine to bind correctly inside the active sites of the neuraminidases of both influenza A/H1N1 and A/H5N1 viruses. The three alkaloids exhibited good binding energies as well as excellent binding modes that were similar to the co-crystallized ligands. On the other hand, consistent with in vitro results, only colchicine could bind correctly against the M2-proton channel of influenza A viruses (IAVs). This might explicate the in vitro antiviral activity of colchicine at the replication stage of the virus replication cycle.

Conclusion

This study highlighted the anti-influenza efficacy of biologically active alkaloids including colchicine. Therefore, these alkaloids should be further characterized in vivo (preclinical and clinical studies) to be developed as anti-IAV agents.
Hybrid-FHR: a multi-modal AI approach for automated fetal acidosis diagnosis
Authors: Zhao Zhidong , Zhu Jiawei , Jiao Pengfei , Wang Jinpeng , Zhang Xiaohong , Lu Xinmiao , Zhang Yefei
Published: January 2024

Background

In clinical medicine, fetal heart rate (FHR) monitoring using cardiotocography (CTG) is one of the most commonly used methods for assessing fetal acidosis. However, as the visual interpretation of CTG depends on the subjective judgment of the clinician, this has led to high inter-observer and intra-observer variability, making it necessary to introduce automated diagnostic techniques.

Methods

In this study, we propose a computer-aided diagnostic algorithm (Hybrid-FHR) for fetal acidosis to assist physicians in making objective decisions and taking timely interventions. Hybrid-FHR uses multi-modal features, including one-dimensional FHR signals and three types of expert features designed based on prior knowledge (morphological time domain, frequency domain, and nonlinear). To extract the spatiotemporal feature representation of one-dimensional FHR signals, we designed a multi-scale squeeze and excitation temporal convolutional network (SE-TCN) backbone model based on dilated causal convolution, which can effectively capture the long-term dependence of FHR signals by expanding the receptive field of each layer’s convolution kernel while maintaining a relatively small parameter size. In addition, we proposed a cross-modal feature fusion (CMFF) method that uses multi-head attention mechanisms to explore the relationships between different modalities, obtaining more informative feature representations and improving diagnostic accuracy.

Results

Our ablation experiments show that the Hybrid-FHR outperforms traditional previous methods, with average accuracy, specificity, sensitivity, precision, and F1 score of 96.8, 97.5, 96, 97.5, and 96.7%, respectively.

Conclusions

Our algorithm enables automated CTG analysis, assisting healthcare professionals in the early identification of fetal acidosis and the prompt implementation of interventions.
The relationship between triglyceride-glucose index and prospective key clinical outcomes in patients hospitalised for coronary artery disease
Authors: Hao Benchuan , Lyu Lyu , Xu Juan , Zhu Xiaoqing , Xu Cui , Gao Weiyang , Qin Ji , Huang Taoke , Ding Yipu , Zhang Ziyue , Yang Yanhui , Liu Hongbin
Published: January 2024

Background

The triglyceride-glucose (TyG) index is regarded as a dependable alternative for assessing insulin resistance (IR), given its simplicity, cost-effectiveness, and strong correlation with IR. The relationship between the TyG index and adverse outcomes in patients with coronary heart disease (CHD) is not well established. This study examines the association of the TyG index with long-term adverse outcomes in hospitalized CHD patients.

Methods

In this single-center prospective cohort study, 3321 patients hospitalized with CHD were included. Multivariate Cox regression models were employed to assess the associations between the TyG index and the incidence of all-cause mortality and major adverse cardiovascular events (MACEs). To examine potential nonlinear associations, restricted cubic splines and threshold analysis were utilized.

Results

During a follow-up period of 9.4 years, 759 patients (22.9%) succumbed to mortality, while 1291 (38.9%) experienced MACEs. Threshold analysis demonstrated a significant “U”-shaped nonlinear relationship with MACEs, with different hazard ratios observed below and above a TyG index of 8.62 (below: HR 0.71, 95% CI 0.50–0.99; above: HR 1.28, 95% CI 1.10–1.48). Notably, an increased risk of all-cause mortality was observed only when the TyG index exceeded 8.77 (HR 1.53, 95% CI 1.19–1.96).

Conclusions

This study reveals a nonlinear association between the TyG index and both all-cause mortality and MACEs in hospitalized CHD patients with CHD. Assessing the TyG index, particularly focusing on individuals with extremely low or high TyG index values, may enhance risk stratification for adverse outcomes in this patient population.
Left main coronary artery morphological phenotypes and its hemodynamic properties
Authors: Wang Qi , Ouyang Hua , Lv Lei , Gui Long , Yang Songran , Hua Ping
Published: January 2024

Background

Atherosclerosis may be linked to morphological defects that lead to variances in coronary artery hemodynamics. Few objective strategies exit at present for generalizing morphological phenotypes of coronary arteries in terms of hemodynamics. We used unsupervised clustering (UC) to classify the morphology of the left main coronary artery (LM) and looked at how hemodynamic distribution differed between phenotypes.

Methods

In this study, 76 LMs were obtained from 76 patients. After LMs were reconstructed with coronary computed tomography angiography, centerlines were used to extract the geometric characteristics. Unsupervised clustering was carried out using these characteristics to identify distinct morphological phenotypes of LMs. The time-averaged wall shear stress (TAWSS) for each phenotype was investigated by means of computational fluid dynamics (CFD) analysis of the left coronary artery.

Results

We identified four clusters (i.e., four phenotypes): Cluster 1 had a shorter stem and thinner branches (n = 26); Cluster 2 had a larger bifurcation angle (n = 10); Cluster 3 had an ostium at an angulation to the coronary sinus and a more curved stem, and thick branches (n = 10); and Cluster 4 had an ostium at an angulation to the coronary sinus and a flatter stem (n = 14). TAWSS features varied widely across phenotypes. Nodes with low TAWSS (L-TAWSS) were typically found around the branching points of the left anterior descending artery (LAD), particularly in Cluster 2.

Conclusion

Our findings demonstrated that UC is a powerful technique for morphologically classifying LMs. Different LM phenotypes exhibited distinct hemodynamic characteristics in certain regions. This morphological clustering method could aid in identifying people at high risk for developing coronary atherosclerosis, hence facilitating early intervention.
A novel methodological approach to participant engagement and policy relevance for community-based primary medical care research during the COVID-19 pandemic in Australia and New Zealand
Authors: Barnes Katelyn , Hall Dykgraaf Sally , O’Brien Kathleen , Douglas Kirsty , Eggleton Kyle , Bui Nam , Wong Sabrina T. , Etz Rebecca S. , Goodyear-Smith Felicity
Published: January 2024

Community-based primary care, such as general practice (GP) or urgent care, serves as the primary point of access to healthcare for most Australians and New Zealanders. Coronavirus disease 2019 (COVID-19) has created significant and ongoing disruptions to primary care. Traditional research methods have contributed to gaps in understanding the experiences of primary care workers during the pandemic. This paper describes a novel research design and method that intended to capture the evolving impact of the COVID-19 pandemic on primary care workers in Australia and New Zealand. Recurrent, rapid cycle surveys were fielded from May 2020 through December 2021 in Australia, and May 2020 through February 2021 in New Zealand. Rapid survey development, fielding, triangulated analysis and dissemination of results allowed close to real-time communication of relevant issues among general practice workers, researchers and policy-makers. A conceptual model is presented to support longitudinal analysis of primary care worker experiences during the COVID-19 pandemic in Australia and New Zealand, and key learnings from applying this novel method are discussed. This paper will assist future research teams in development and execution of policy-relevant research in times of change and may inform further areas of interest for COVID-19 research in primary care.
A novel sub-regional radiomics model to predict immunotherapy response in non-small cell lung carcinoma
Authors: Peng Jie , Zou Dan , Zhang Xudong , Ma Honglian , Han Lijie , Yao Biao
Published: January 2024

Background

Identifying precise biomarkers of immunotherapy response for non-small cell lung carcinoma (NSCLC) before treatment is challenging. This study aimed to construct and investigate the potential performance of a sub-regional radiomics model (SRRM) as a novel tumor biomarker in predicting the response of patients with NSCLC treated with immune checkpoint inhibitors, and test whether its predictive performance is superior to that of conventional radiomics, tumor mutational burden (TMB) score and programmed death ligand-1 (PD-L1) expression.

Methods

We categorized 264 patients from retrospective databases of two centers into training (n = 159) and validation (n = 105) cohorts. Radiomic features were extracted from three sub-regions of the tumor region of interest using the K-means method. We extracted 1,896 features from each sub-region, resulting in 5688 features per sample. The least absolute shrinkage and selection operator regression method was used to select sub-regional radiomic features. The SRRM was constructed and validated using the support vector machine algorithm. We used next-generation sequencing to classify patients from the two cohorts into high TMB (≥ 10 muts/Mb) and low TMB (< 10 muts/Mb) groups; immunohistochemistry was performed to assess PD-L1 expression in formalin-fixed, paraffin-embedded tumor sections, with high expression defined as ≥ 50% of tumor cells being positive. Associations between the SRRM and progression-free survival (PFS) and variant genes were assessed.

Results

Eleven sub-regional radiomic features were employed to develop the SRRM. The areas under the receiver operating characteristic curve (AUCs) of the proposed SRRM were 0.90 (95% confidence interval [CI] 0.84−0.96) and 0.86 (95% CI 0.76−0.95) in the training and validation cohorts, respectively. The SRRM (low vs. high; cutoff value = 0.936) was significantly associated with PFS in the training (hazard ratio [HR] = 0.35 [0.24−0.50], P < 0.001) and validation (HR = 0.42 [0.26−0.67], P = 0.001) cohorts. A significant correlation between the SRRM and three variant genes (H3C4, PAX5, and EGFR) was observed. In the validation cohort, the SRRM demonstrated a higher AUC (0.86, P < 0.001) than that for PD-L1 expression (0.66, P = 0.034) and TMB score (0.54, P = 0.552).

Conclusions

The SRRM had better predictive performance and was superior to conventional radiomics, PD-L1 expression, and TMB score. The SRRM effectively stratified the progression-free survival (PFS) risk among patients with NSCLC receiving immunotherapy.
Risk factors for postoperative delirium in patients with Stanford type A aortic dissection: a systematic review and meta-analysis
Authors: Lu Shan , Jiang Yi , Meng Fangfang , Xie Xiaoli , Wang Dongjin , Su Yunyan
Published: January 2024

Background

Delirium is a common postoperative complication among patients who undergo Stanford Type A aortic dissection (TAAD). It is associated with increased mortality, as well as other serious surgical outcomes. This study aimed to analyze the risk factors for delirium in TAAD patients.

Methods

Pubmed, Web of science, Embase, the Cochrane Library and CINAHL were searched by computer to collect literatures on risk factors for postoperative delirium (POD) after TAAD. The retrieval period was from the establishment of the database to September 2022. After literature screening, two reviewers independently assessed the quality of the included studies using the Newcastle–Ottawa Scale (NOS). Data were extracted according to standard protocols, and then meta-analysis was performed using Revman 5.3 software.

Results

A total of 9 articles, comprising 7 case–control studies and 2 cohort studies, were included in this analysis. The sample size consisted of 2035 patients. POD was associated with increased length of ICU stay (MD 3.24, 95% CI 0.18–6.31, p = 0.04) and length of hospital stay (MD 9.34, 95% CI 7.31–11.37, p < 0.0001) in TAAD patients. Various perioperative risk factors were identified, including age (MD 4.40, 95% CI 2.06–6.73, p = 0.0002), preoperative low hemoglobin levels (MD − 4.44, 95% CI − 7.67 to − 1.20, p = 0.007), body mass index (MD 0.92, 95% CI 0.22–1.63, p = 0.01), history of cardiac surgery (OR 3.06, 95% CI 1.20–7.83, p = 0.02), preoperative renal insufficiency (OR 2.50, 95% CI 1.04–6.04, p = 0.04), cardiopulmonary bypass (CPB) duration (MD 19.54, 95% CI 6.34–32.74, p = 0.004), surgery duration (MD 44.88, 95% CI 5.99–83.78, p = 0.02), mechanical ventilation time (SMD 1.14, 95% CI 0.34–1.94, p = 0.005), acute physiology and chronic health evaluation (APACHE II) score (MD 2.67, 95% CI 0.37–4.98, p = 0.02), postoperative renal insufficiency (OR 2.82, 95% CI 1.40–5.68, p = 0.004), electrolyte disturbance (OR 6.22, 95% CI 3.08–12.54, p < 0.0001) and hypoxemia (OR 3.56, 95% CI 1.70–7.44, p = 0.0007).

Conclusions

POD can prolong ICU stay and hospital stay in TAAD patients. This study identified a number of risk factors for POD after TAAD, suggesting the possibility of early identification of high-risk patients using relevant data.