bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tobacco smoke and all-cause mortality and premature death in China: a cohort study
Authors: Zhang Liang , Ma Yonghong , Men Ke , Li Chao , Zhang Zhuo , Shi Guoshuai 
Published: December 2023

Abstract
Background
Tobacco smoke is associated with several diseases, and identified as the second leading risk factor for death from any cause worldwide. The relationship of tobacco smoke to mortality or premature death is not yet available from contemporary cohorts after 2010 in China. This study aimed to investigate the smoking behavior and the relationship of tobacco smoke to mortality and premature death among a nationally representative cohort starting from 2011 in China.

Methods
The nationally representative datasets (China Health and Retirement Longitudinal Study, CHARLS, 2011–2012) was employed and linked with follow-up data (2013). CHARLS was an ongoing nationally representative survey, which longitudinally followed up subjects aged over 45 years. Smoking status (non-smoker, ex-smoker, smoker, pack-years of smoking, age at starting and ceasing smoking) was used as independent variable, and all-cause mortality, premature death (defined as mortality before age 72.7 years in men and 76.9 years in women) were used as dependent variables. The Cox’s proportional hazards regression mode was used to estimate the effect of tobacco smoke and pack-years of smoking on all-cause mortality and premature death.

Results
A total of 16,701 subjects were included. The association between tobacco smoker (hazard ratio [HR] = 1.37, 95%CI = 1.02, 1.83) / ex-smoker (HR = 1.75, 95%CI = 1.24, 2.46) and all-cause mortality was significant. Tobacco smoker (HR = 1.58, 95%CI = 1.04, 2.39) and ex-smoker (HR = 2.25, 95%CI = 1.38, 3.66) was associated with increase in the risk of premature death. Pack-years of smoking ≥ 30 was associated with increased risk of premature death compared with non-smokers in total (HR = 1.59, 95%CI = 1.03, 2.43) and women (HR = 3.38, 95%CI = 1.22, 9.38). Additionally, our results also revealed that there was a linear trend between pack-years of smoking and premature death in total (P = 0.002) and women (P = 0.010).

Conclusion
This study found a negative effect of smoking status on all-cause mortality and premature death among a contemporary and nationally representative data in China. The correlation between pack-years of smoking and premature death and the trend of pack-years of smoking with premature death was also identified.
Phytochemical profile and antimicrobial activity of essential oils from two Syzygium species against selected oral pathogens
Authors: Salem Sahar S. , Elsayed Heba E. , Shabana Samah , Khazaal Mohamed T. , Moharram Fatma A. 
Published: December 2023

Abstract
Background
The genus Syzygium (Myrtaceae) comprises several essential oil-rich species that are utilized traditionally for treating tooth infections and toothache. The current study aimed to extract essential oils (EOs) from the leaves of Syzygium samarangense and Syzygium malaccense cultivated in Egypt for the first time and screen their antimicrobial potential against oral-related pathogens.

Methods
The intended EOs were extracted using hydrodistillation (HD) by boiling fresh leaves with distilled water; supercritical fluid (SF) by extracting the dried leaves using supercritical CO2 at 40 °C and 150 bar; and the headspace (HS) in which the fresh leaves were heated in a glass vial and the vaporized aroma were analyzed. The volatile constituents were analyzed using GC/MS and identified by comparing the experimental Kovats' retention indices with the literature. The antimicrobial activity was assessed against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Candida albicans using agar diffusion, microwell dilution, and biofilm formation assays. Statistical significance (p < 0.05) was determined by applying one-way ANOVA and Duncan's post hoc test.

Results
The yield of the extracted EOs differs between the applied methods, and the SF approach harvested the maximum (0.52–0.46%). The GC–MS analysis of SF EOs revealed a discrepancy between the two species. Since S. malaccense showed an abundance of hydrocarbons represented mainly by squalene (60.60%), S. samarangense was deemed to have oxygenated sesquiterpenes exemplified in globulol (52.09%). On the other side, the HD and HS EOs were sequentially comparable, while differed in the percentage of their majors. γ-terpinene (33.06%) pioneered the HS-derived aroma of S. malaccense, while S. samarangense was abundant with α-pinene (30.18%). Concurrently, the HD EOs of S. malaccense and S. samarangense were commonly denoted by caryophyllene oxide (8.19%-18.48%), p-cymene (16.02%- 19.50%), and γ-terpinene (12.20%-17.84). Ultimately, both species EOs exhibited broad-spectrum antimicrobial potential, although the HD EO was more potent than the SF EO. The HD EOs of both species potently inhibited the growth of E. coli (MIC 3.75 µL/mL) and suppressed C. albicans biofilm formation by 83.43 and 87.27%, respectively. The SF-EOs efficiently suppressed the biofilm formation of Gram-positive bacteria by 76.45%-82.95%.

Conclusion
EOs extracted from both species by different methods possessed a unique blend of volatile components with broad-spectrum antimicrobial activity. They were promoted as bioactive hits for controlling oral infections, however further investigations concerning their safety in clinical settings are needed.
“None of us are lying”: an interpretive description of the search for legitimacy and the journey to access quality health services by individuals living with Long COVID
Authors: Brehon Katelyn , Miciak Maxi , Hung Pam , Chen Shu-Ping , Perreault Kadija , Hudon Anne , Wieler Marguerite , Hunter Simone , Hoddinott Lance , Hall Mark , Churchill Katie , Brown Darren A. , Brown Cary A. , Bostick Geoffrey , Skolnik Kate , Lam Grace , Weatherald Jason , Gross Douglas P. 
Published: December 2023

Abstract
Background
Understanding of Long COVID has advanced through patient-led initiatives. However, research about barriers to accessing Long COVID services is limited. This study aimed to better understand the need for, access to, and quality of, Long COVID services. We explored health needs and experiences of services, including ability of services to address needs.

Methods
Our study was informed by the Levesque et al.’s (2013) “conceptual framework of access to health care.” We used Interpretive Description, a qualitative approach partly aimed at informing clinical decisions. We recruited participants across five settings. Participants engaged in one-time, semi-structured, virtual interviews. Interviews were transcribed verbatim. We used reflexive thematic analysis. Best practice to ensure methodological rigour was employed.

Results
Three key themes were generated from 56 interviews. The first theme illustrated the rollercoaster-like nature of participants’ Long COVID symptoms and the resulting impact on function and health. The second theme highlighted participants’ attempts to access Long COVID services. Guidance received from healthcare professionals and self-advocacy impacted initial access. When navigating Long COVID services within the broader system, participants encountered barriers to access around stigma; appointment logistics; testing and ‘normal’ results; and financial precarity and affordability of services. The third theme illuminated common factors participants liked and disliked about Long COVID services. We framed each sub-theme as the key lesson (stemming from all likes and dislikes) that, if acted upon, the health system can use to improve the quality of Long COVID services. This provides tangible ways to improve the system based directly on what we heard from participants.

Conclusion
With Long COVID services continuously evolving, our findings can inform decision makers within the health system to better understand the lived experiences of Long COVID and tailor services and policies appropriately.
BMC3PM: bioinformatics multidrug combination protocol for personalized precision medicine and its application in cancer treatment
Authors: Mokhtari Majid , Khoshbakht Samane , Akbari Mohammad Esmaeil , Moravveji Sayyed Sajjad 
Published: December 2023

Abstract
Background
In recent years, drug screening has been one of the most significant challenges in the field of personalized medicine, particularly in cancer treatment. However, several new platforms have been introduced to address this issue, providing reliable solutions for personalized drug validation and safety testing. In this study, we developed a personalized drug combination protocol as the primary input to such platforms.

Methods
To achieve this, we utilized data from whole-genome expression profiles of 6173 breast cancer patients, 312 healthy individuals, and 691 drugs. Our approach involved developing an individual pattern of perturbed gene expression (IPPGE) for each patient, which was used as the basis for drug selection. An algorithm was designed to extract personalized drug combinations by comparing the IPPGE and drug signatures. Additionally, we employed the concept of drug repurposing, searching for new benefits of existing drugs that may regulate the desired genes.

Results
Our study revealed that drug combinations obtained from both specialized and non-specialized cancer medicines were more effective than those extracted from only specialized medicines. Furthermore, we observed that the individual pattern of perturbed gene expression (IPPGE) was unique to each patient, akin to a fingerprint.

Conclusions
The personalized drug combination protocol developed in this study offers a methodological interface between drug repurposing and combination drug therapy in cancer treatment. This protocol enables personalized drug combinations to be extracted from hundreds of drugs and thousands of drug combinations, potentially offering more effective treatment options for cancer patients.
Association of lncRNA THRIL, HOTAIR genes variations and expression levels with pulmonary tuberculosis
Authors: Wang Li-Jun , Li Rui , Zhang Tian-Ping , Li Hong-Miao 
Published: December 2023

Abstract
Background
Long non-coding RNA (lncRNA) has been implicated in the pathogenesis of pulmonary tuberculosis (PTB). This study aims to investigate the involvement of lncRNA THRIL and HOTAIR gene single nucleotide polymorphisms (SNPs) and their expression levels in PTB susceptibility.

Methods
A total of 456 PTB patients and 464 healthy controls participated in our study. we genotyped six SNPs of THRIL and HOTAIR genes using an improved multiple ligase detection reaction (iMLDR). Additionally, real-time reverse-transcriptase polymerase chain reaction was employed to detect the expression levels of THRIL and HOTAIR in peripheral blood mononuclear cells (PBMC) from 78 PTB patients and 84 healthy controls.

Results
No significant differences in allele and genotype frequencies were observed for THRIL rs1055472, rs11058000, and HOTAIR rs12427129, rs1899663, rs4759314, and rs7958904 polymorphisms between PTB patients and healthy controls (all P > 0.05). Moreover, genotype frequencies of all SNPs did not show any association with PTB susceptibility in the dominant–recessive model. However, the frequencies of rs7958904 CC genotype and C allele in the HOTAIR gene were significantly correlated with leukopenia in PTB patients. Furthermore, the expression levels of the HOTAIR gene were significantly elevated in PTB patients compared to controls.

Conclusions
Our study indicates that THRIL and HOTAIR gene SNPs might not contribute to PTB susceptibility, while the level of HOTAIR was increased in PTB patients.
Artificial intelligence-driven new drug discovery targeting serine/threonine kinase 33 for cancer treatment
Authors: Tran Na Ly , Kim Hyerim , Shin Cheol-Hee , Ko Eun , Oh Seung Ja 
Published: December 2023

Abstract
Background
Artificial intelligence (AI) is capable of integrating a large amount of related information to predict therapeutic relationships such as disease treatment with known drugs, gene expression, and drug-target binding. AI has gained increasing attention as a promising tool for next-generation drug development.

Methods
An AI method was used for drug repurposing and target identification for cancer. Among 8 survived candidates after background checking, N-(1-propyl-1H-1,3-benzodiazol-2-yl)-3-(pyrrolidine-1-sulfonyl) benzamide (Z29077885) was newly selected as an new anti-cancer drug, and the anti-cancer efficacy of Z29077885 was confirmed using cell viability, western blot, cell cycle, apoptosis assay in MDA-MB 231 and A549 in vitro. Then, anti-tumor efficacy of Z29077885 was validated in an in vivo A549 xenograft in BALB/c nude mice.

Results
First, we discovered an antiviral agent, Z29077885, as a new anticancer drug candidate using the AI deep learning method. Next, we demonstrated that Z29077885 inhibits Serine/threonine kinase 33 (STK33) enzymatic function in vitro and showed the anticancer efficacy in various cancer cells. Then, we found enhanced apoptosis via S-phase cell cycle arrest as the mechanism underlying the anticancer efficacy of Z29077885 in both lung and breast cancer cells. Finally, we confirmed the anti-tumor efficacy of Z29077885 in an in vivo A549 xenograft.

Conclusions
In this study, we used an AI-driven screening strategy to find a novel anticancer medication targeting STK33 that triggers cancer cell apoptosis and cell cycle arrest at the s phase. It will pave a way to efficiently discover new anticancer drugs.
Effects of vibration therapy for post-stroke spasticity: a systematic review and meta-analysis of randomized controlled trials
Authors: Zeng Duchun , Lei Wei , Kong Yurou , Ma Fenghao , Zhao Kun , Ye Xiangming , Tan Tongcai 
Published: December 2023

Abstract
Background
The efficacy of vibration therapy (VT) in people with post-stroke spasticity (PSS) remains uncertain. This study aims to conduct a comprehensive meta-analysis to assess the effectiveness of VT in PSS.

Methods
PubMed, Embase, Cochrane Library, Physiotherapy Evidence Database, and Web of Science were searched from inception to October 2022 for randomized controlled trials (RCTs) of VT in people with PSS. The primary outcome was spasticity, and secondary outcomes included pain, motor function, gait performance, and adverse events. A meta‑analysis was performed by pooling the standardized mean difference (SMD) with 95% confidence intervals (CI).

Results
A total of 12 studies met the inclusion criteria. Overall, VT had significant effects on reducing spasticity (SMD = − 0.77, 95% CI − 1.17 to − 0.36, P < 0.01) and pain (SMD =  − 1.09, 95% CI − 1.74 to − 0.45, P < 0.01), and improving motor function (SMD = 0.42, 95% CI 0.21 to 0.64, P < 0.01) in people with PSS. However, VT had no significant effect on gait performance (SMD =  − 0.23, 95% CI − 0.56–0.10). In addition, subgroup differences in short-term anti-spasticity effects between different vibration subtypes, vibration frequencies, vibration durations, frequency of sessions, control therapy, spasticity distribution, and population classification were not significant.

Conclusion
We found that VT significantly alleviated spasticity and pain in people with PSS and improved motor function, but its effect on gait performance was unclear. However, further studies are needed to validate these findings.
Delineating family needs in the transition from hospital to home for children with medical complexity: part 1, a meta-aggregation of qualitative studies
Authors: van de Riet L. , Alsem M. W. , van der Leest E. C. , van Etten-Jamaludin F. S. , Maaskant J. M. , van Woensel J. B. M. , van Karnebeek C. D. 
Published: December 2023

Abstract
Background
Advances in diagnostic and therapeutic interventions for rare diseases result in greater survival rates, with on the flipside an expanding group of children with medical complexity (CMC). When CMC leave the protective hospital environment to be cared for at home, their parents face many challenges as they take on a new role, that of caregiver rather than care-recipient. However, an overview of needs and experiences of parents of CMC during transition from hospital-to-home (H2H) is lacking, which hampers the creation of a tailored H2H care pathway. Here we address this unmet medical need by performing a literature review to systematically identify, assess and synthesize all existing qualitative evidence on H2H transition needs of CMC parents.

Methods
An extensive search in Medline, PsychINFO and CINAHL (up to September 2022); selection was performed to include all qualitative studies describing parental needs and experiences during H2H transition of CMC. All papers were assessed by two independent investigators for methodological quality before data (study findings) were extracted and pooled. A meta-aggregation method categorized the study findings into categories and formulated overarching synthesized findings, which were assigned a level of confidence, following the ConQual approach.

Results
The search yielded 1880 papers of which 25 met eligible criteria. A total of 402 study findings were extracted from the included studies and subsequently aggregated into 50 categories and 9 synthesized findings: (1) parental empowerment: shifting from care recipient to caregiver (2) coordination of care (3) communication and information (4) training skills (5) preparation for discharge (6) access to resources and support system (7) emotional experiences: fatigue, fear, isolation and guilt (8) parent-professional relationship (9) changing perspective: finding new routines and practices. The overall ConQual Score was low for 7 synthesized findings and very low for 2 synthesized findings.

Conclusions
Despite the variability in CMC symptoms and underlying (rare disease) diagnoses, overarching themes in parental needs during H2H transition emerged. We will augment this new knowledge with an interview study in the Dutch setting to ultimately translate into an evidence-based tailored care pathway for implementation by our interdisciplinary team in the newly established ‘Jeroen Pit Huis’, an innovative care unit which aims for a safe and sustainable H2H transition for CMC and their families.
Leptospirosis in Malaysia: current status, insights, and future prospects
Authors: Philip Noraini , Ahmed Kamruddin 
Published: December 2023

AbstractAmong zoonotic infections, leptospirosis has a worldwide distribution and high prevalence in tropical regions. It has a broad clinical presentation from mild to severe, life-threatening infection. Leptospires, the etiological agent of leptospirosis, are found in varied ecological niches and animal species, providing a significant source of human infection. This review aims to provide the current status of leptospirosis in Malaysia and the direction for future studies. The literature search for this review was performed using PubMed, Web of Sciences, and Google Scholar databases. The incidence of leptospirosis in Malaysia from 2004 to 2020 varied; however, a large number of cases occurred during floods. Leptospira has been isolated from wild and domestic animals as well as from the environment; among them, several novel species have been identified. In Malaysia, leptospirosis infection and death were mostly associated with recreational and non-recreational water activities. Despite the endemicity of leptospirosis, the public’s knowledge, attitude, and practice level are relatively low in this country. More studies are needed in Malaysia to explore the extent of leptospirosis in different settings and locations.
Gut microbiota-related metabolite alpha-linolenic acid mitigates intestinal inflammation induced by oral infection with Toxoplasma gondii
Authors: Yang Jing , Liu Songhao , Zhao Qian , Li Xiaobing , Jiang Kangfeng 
Published: December 2023

Abstract
Background
Oral infection with cysts is the main transmission route of Toxoplasma gondii (T. gondii), which leads to lethal intestinal inflammation. It has been widely recognized that T. gondii infection alters the composition and metabolism of the gut microbiota, thereby affecting the progression of toxoplasmosis. However, the potential mechanisms remain unclear. In our previous study, there was a decrease in the severity of toxoplasmosis after T. gondii α-amylase (α-AMY) was knocked out. Here, we established mouse models of ME49 and Δα-amy cyst infection and then took advantage of 16S rRNA gene sequencing and metabolomics analysis to identify specific gut microbiota-related metabolites that mitigate T. gondii-induced intestinal inflammation and analyzed the underlying mechanism.

Results
There were significant differences in the intestinal inflammation between ME49 cyst- and Δα-amy cyst-infected mice, and transferring feces from mice infected with Δα-amy cysts into antibiotic-treated mice mitigated colitis caused by T. gondii infection. 16S rRNA gene sequencing showed that the relative abundances of gut bacteria, such as Lactobacillus and Bacteroides, Bifidobacterium, [Prevotella], Paraprevotella and Macellibacteroides, were enriched in mice challenged with Δα-amy cysts. Spearman correlation analysis between gut microbiota and metabolites indicated that some fatty acids, including azelaic acid, suberic acid, alpha-linolenic acid (ALA), and citramalic acid, were highly positively correlated with the identified bacterial genera. Both oral administration of ALA and fecal microbiota transplantation (FMT) decreased the expression of pro-inflammatory cytokines and restrained the MyD88/NF-κB pathway, which mitigated colitis and ultimately improved host survival. Furthermore, transferring feces from mice treated with ALA reshaped the colonization of beneficial bacteria, such as Enterobacteriaceae, Proteobacteria, Shigella, Lactobacillus, and Enterococcus.

Conclusions
The present findings demonstrate that the host gut microbiota is closely associated with the severity of T. gondii infection. We provide the first evidence that ALA can alleviate T. gondii-induced colitis by improving the dysregulation of the host gut microbiota and suppressing the production of pro-inflammatory cytokines via the MyD88/NF-κB pathway. Our study provides new insight into the medical application of ALA for the treatment of lethal intestinal inflammation caused by Toxoplasma infection.