bluuebunny/crossref_metadata_2025 huggingface dataset:
LMP2 and TAP2 impair tumor growth and metastasis by inhibiting Wnt/β-catenin signaling pathway and EMT in cervical cancer
Authors: Cheng Zhengyan , Wang Hongbo , Yang Zewei , Li Jiaxu , Chen Xing
Published: November 2023

Background

The roles of low molecular mass polypeptide 2 (LMP2) and transporter-associated with antigen processing (TAP2) in tumorigenesis are controversial. Here we aimed to explore the effect of LMP2 and TAP2 on the oncogenesis and metastasis of cervical cancer cells.

Methods

The expressions of LMP2 and TAP2 in cervical cancer and normal tissues were determined by qPCR. Plate colony formation, cell counting kit-8 analysis and in vivo tumor xenograft assays were used to detect the tumor growth. Wound healing and transwell assays were used to detect the metastasis of cervical cancer. Gelatin zymography and western blotting assays were used to detect the effect of LMP2 and TAP2 on the EMT and Wnt/β-catenin pathway in cervical cancer cells.

Results

In the present study, we reported that LMP2 and TAP2 levels were overexpressed in cervical cancer. Overexpression of LMP2 and TAP2 impaired the proliferation of Hela cells. In vivo studies substantiated that LMP2 and TAP2 antagonized tumor growth. Likewise, LMP2 and TAP2 overexpression decreased the migration and invasion ability of Hela cells by regulating the process of epithelial-mesenchymal transition (EMT). Mechanically, LMP2 and TAP2 subverted the protein abundance of Wnt1 and β-catenin, thereby downregulating their downstream targets Cyclin D1 and c-Myc. In addition, Wnt1 overexpression partially rescued the observed consequences of ectopic expression of LMP2 and TAP2 in cervical cancer cells. Taken together, our study revealed that LMP2 and TAP2 suppress the oncogenesis and metastasis of cervical cancer cells by Wnt/β-catenin pathway and altering EMT.

Conclusion

LMP2 and TAP2 may inhibit the oncogenesis and metastasis of cervical cancer cells by inhibiting the process of EMT and the Wnt/β-catenin signaling pathway, which may provide important insight into prospective targets for the treatment of cervical cancer.
Evaluation of a person-centred, nurse-led model of care delivering hepatitis C testing and treatment in priority settings: a mixed-methods evaluation of the Tasmanian Eliminate Hepatitis C Australia Outreach Project, 2020–2022
Authors: Dawe Joshua , Hughes Megan , Christensen Shannon , Walsh Louisa , Richmond Jacqueline A. , Pedrana Alisa , Wilkinson Anna L. , Owen Louise , Doyle Joseph S. ,   on behalf of the EC Australia Partnership, Hellard Margaret , Stoove Mark , Scott Nick , Howell Jess , Selvey Linda , Michaels Jessica , Crawford Sione , Fowlie Carrie , Singhal Shweta , Davies Jane , Manu Geoff , Ward James , Drenkhahn Geoff , Bastian Lisa , Dore Greg , Bryant Mellissa , Marshall Catherine , Llyod Andrew , McMahon Maria , Sattell Garry , Casey Dawn , Shaw David , Rees Tom , Thompson Alex
Published: November 2023

Introduction

Australia has experienced sustained reductions in hepatitis C testing and treatment and may miss its 2030 elimination targets. Addressing gaps in community-based hepatitis C prescribing in priority settings that did not have, or did not prioritise, hepatitis C testing and treatment care pathways is critical.

Methods

The Tasmanian Eliminate Hepatitis C Australia Outreach Project delivered a nurse-led outreach model of care servicing hepatitis C priority populations in the community through the Tasmanian Statewide Sexual Health Service, supported by the Eliminating Hepatitis C Australia partnership. Settings included alcohol and other drug services, needle and syringe programs and mental health services. The project provided clients with clinical care across the hepatitis C cascade of care, including testing, treatment, and post-treatment support and hepatitis C education for staff.

Results

Between July 2020 and July 2022, a total of 43 sites were visited by one Clinical Nurse Consultant. There was a total of 695 interactions with clients across 219 days of service delivery by the Clinical Nurse Consultant. A total of 383 clients were tested for hepatitis C (antibody, RNA, or both). A total of 75 clients were diagnosed with hepatitis C RNA, of which 95% (71/75) commenced treatment, 83% (62/75) completed treatment and 52% (39/75) received a negative hepatitis C RNA test at least 12 weeks after treatment completion.

Conclusions

Providing outreach hepatitis C services in community-based services was effective in engaging people living with and at-risk of hepatitis C, in education, testing, and care. Nurse-led, person-centred care was critical to the success of the project. Our evaluation underscores the importance of employing a partnership approach when delivering hepatitis C models of care in community settings, and incorporating workforce education and capacity-building activities when working with non-specialist healthcare professionals.
Will tobacco price increases lead more people who smoke to vape? The results from a discrete choice experiment amongst U.S. adults
Authors: Zarate-Gonzalez Gilda , Brown Paul , Cameron Linda D. , Song Anna V.
Published: November 2023

Objective

To understand the extent to which people who smoke, people who vape and nonsmokers would switch between smoking cigarettes and vaping in response to policies (price increases, restrictions on nicotine, places, and information on addictiveness and/or health risks) aimed at decreasing tobacco use by people who smoke and vaping by nonsmokers.

Design

A total of 525 adults aged 18 to 88 years completed a discrete choice survey of 16 choices between two smoking/vaping alternatives. Analysis was conducted using conditional logistic regression for the entire sample and stratified by nonsmokers, people who smoke, and people who vape.

Results

The results suggest that most people who vape also smoke. Nonsmokers were more favorable to vaping and were concerned about long-term health risks and cost associated with vaping. Marginal analysis suggests that price increases will have only modest success in moving people who smoke to start vaping or encouraging people who vape to vape rather than use cigarettes. Nonsmokers are not very sensitive to price changes but are sensitive to information about health impacts.

Conclusions

Findings indicate that increasing the price of cigarettes would lead to a limited increase in the probability of people who smoke switch to vaping. The study advances our understanding of the views of current nonsmokers toward cigarettes and vaping, suggesting that price increases and increased knowledge of addiction would likely deter nonsmokers from vaping. Changing the amount of nicotine associated with smoking would increase the probability of vaping slightly and have little impact on nonsmokers or vaping preferences, but the most significant change would come from increasing the perceptions of the risk of smoking.
Integration of point-of-care screening for type 2 diabetes mellitus and hypertension into the COVID-19 vaccine programme in Johannesburg, South Africa
Authors: Brennan Alana T , Vetter Beatrice , Masuku Sithabiso D , Mtshazo Bukelwa , Mashabane Nkuli , Sokhela Simiso , Venter Willem DF , Kao Kekeletso , Meyer-Rath Gesine
Published: November 2023

Background

South Africa grapples with a substantial burden of non-communicable diseases (NCDs), particularly type 2 diabetes (diabetes) and hypertension. However, these conditions are often underdiagnosed and poorly managed, further exacerbated by the strained primary healthcare (PHC) system and the disruptive impact of the COVID-19 pandemic. Integrating NCD screening with large-scale healthcare initiatives, such as COVID-19 vaccination campaigns, offers a potential solution, especially in low- and middle-income countries (LMICs). We investigated the feasibility and effectiveness of this integration.

Methods

A prospective cohort study was conducted at four government health facilities in Johannesburg, South Africa. NCD screening was incorporated into the COVID-19 vaccination campaign. Participants underwent COVID-19 rapid tests, blood glucose checks, blood pressure assessments, and anthropometric measurements. Those with elevated blood glucose or blood pressure values received referrals for diagnostic confirmation at local PHC centers.

Results

Among 1,376 participants screened, the overall diabetes prevalence was 4.1%, combining previously diagnosed cases and newly identified elevated blood glucose levels. Similarly, the hypertension prevalence was 19.4%, comprising pre-existing diagnoses and newly detected elevated blood pressure cases. Notably, 46.1% of participants displayed waist circumferences indicative of metabolic syndrome, more prevalent among females. Impressively, 7.8% of all participants screened were potentially newly diagnosed with diabetes or hypertension. Approximately 50% of individuals with elevated blood glucose or blood pressure successfully linked to follow-up care within four weeks.

Conclusion

Our study underscores the value of utilizing even brief healthcare interactions as opportunities for screening additional health conditions, thereby aiding the identification of previously undiagnosed cases. Integrating NCD screenings into routine healthcare visits holds promise, especially in resource-constrained settings. Nonetheless, concerted efforts to strengthen care linkage are crucial for holistic NCD management and control. These findings provide actionable insights for addressing the NCD challenge and improving healthcare delivery in LMICs.
Construction of a model for adolescent physical and mental health promotion based on the multiple mediating effects of general self-efficacy and sleep duration
Authors: Dong Ru-bao , Dou Kai-yun , Luo Jie
Published: November 2023

We developed a model for promoting adolescent physical and mental health (MH) to investigate the integrated pathways of physical activity (PA), MH, general self-efficacy (GSE), and sleep duration (SD) promotion among adolescents in China. The research hypotheses were tested using questionnaires, descriptive statistics, and validated factor analysis. The mean age of the respondents was 14.94 ± 1.76 years, the PA level was 2.49 [95% confidence interval (CI): 2.46–2.53], the GSE score was 2.60 (95% CI: 2.57–2.64), the SD was 436.52 min/day (95% CI: 432.89–440.15), and the total mean MH score was 1.72 (95% CI: 1.69–1.76) (model fitness index: χ2/df = 1.295, comparative fit index = 0.999, Tucker–Lewis index = 0.997, root mean square error of approximation = 0.014, standardized root mean square residual = 0.007). The SD accounted for 46.85% of the mediating effect. The adolescents exhibited moderately low PA levels, severe SD deficits, and high rates of overall MH abnormalities. Consequently, the constructed model for promoting adolescent physical health and MH was confirmed to be reliable; GSE and SD are significant factors mediating MH promotion.
Factors influencing nasal airway pressure and comfort in high-flow nasal cannula oxygen therapy: a volunteer study
Authors: Zhao Enqi , Zhou Yilong , He Chunwei , Ma Dedong
Published: November 2023

Background

High-flow nasal cannula (HFNC) oxygen therapy is essentially a constant-flow, noninvasive respiratory support system similar to a noninvasive ventilator operating in constant-flow mode. The clinical outcome of HFNC oxygen therapy is strongly associated with the pressure generated by high-flow gas and the patient’s comfort level. This study was performed to explore the relevant factors affecting pressure and comfort of HFNC oxygen therapy in vivo.

Methods

Thirty-five healthy volunteers were enrolled in the trial. They underwent placement of nasal cannulas of various inner diameters (3, 4 or 5 mm) and treatment with different HFNC devices [HFT-300 (Weishengkang Medical Technology Co., Ltd., Jiangsu China) or H-80 M (BMC Medical Co., Ltd., Beijing China)],and the nasal airway pressure and comfort were assessed. Multiple linear regression was used to determine predictors of airway pressure.

Results

Multiple linear regression showed that the end-expiratory pressure was associated with the flow rate, sex, height, and cannula size. The end-expiratory pressure increased by 0.6 cmH2O per 1-mm increase in cannula diameter, decreased by 0.3 cmH2O per 10-cm increase in participant height (with a 0.35 cmH2O decrease for men), and increased by 1 cmH2O when the flow rate increased by 10 L/min (R2 = 0.75,P < 0.05 for all variables in model). In addition, the pressure generated by the H-80 M device was higher than that generated by the HFT-300 device (P < 0.05). Discomfort manifested as difficulty in expiration, and its severity increased as the cannula diameter increased; however there was no significant difference in comfort between the two HFNC devices (P > 0.05).

Conclusion

In volunteers undergoing HFNC oxygen therapy, the nasal cannula diameter, flow rate, sex, height, and device model can affect the nasal airway pressure, and the nasal catheter diameter and flow rate can affect comfort. These factors should be given close attention in clinical practice.

Trial registration

ChiCTR2300068313 (date of first registration: 14 February 2023, https://www.chictr.org.cn).
Comparative study of pulmonary functions test among different substances abusers
Authors: Mohamed Hana Salah Musa , Ali Ibrahim Abdelrhim
Published: November 2023

Background

Substance use is a problem that affects people all over the world and is prevalent in different age groups. The lungs in particular, with their unique exposure to the environment and the bloodstream, are vulnerable to damage from substance use and can affect lung function. Efforts have generally focused on cigarettes, while there is little research on different substances of use. The study aimed to detect changes in pulmonary function tests in different substance users.

Methods

An analytical cross-sectional study was carried out among different substance users at the Abdalaal Elidridi Psychiatric Hospital. A total of 60 adults were included: 16 cannabis users, 16 heroin users, 16 methamphetamine users, and 12 alcohol users. Participants used only one substance. Height and weight were measured, and BMI was calculated. For each participant, pulmonary function tests (PFTs) including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC ratio and peak expiratory flow rate (PEFR) were measured using an electronic spirometer, and the results were compared with normal reference values for Sudanese subjects matched for age, sex, and height.

Results

A high prevalence of lung function abnormalities (100.0%) is seen in all abusers. Obstructive lung disease is found in 80.0% of patients, and restrictive lung disease is found in 20.0% of cases. The measured FEV1/FVC ratio in different substance groups was lower than the expected normal values of (88.2 ± 2.9%). The mean FEV1/FVC ratio of alcohol was (83.6 ± 7.6%), for heroin, it was (77.3 ± 15.8%), for methamphetamine, it was (77.7 ± 17.8%) and for cannabis, it was (71.03 ± 11.3%), the latter was significantly lower than the other two groups (P < 0.001). Duration of substance use was inversely correlated with the FEV1/FVC ratio (r = -0.378, P 0.001), indicating that a longer duration of substance use correlates with lower FEV1/FVC ratios.

Conclusions

Obstructive lung abnormalities are frequent in substance abusers. All types of substances have a major deleterious effect on PFTs and harm the respiratory system. More action should be taken to address the effects of substances on the lungs. Awareness, early detection, and intervention are essential.
Associations of early pregnancy serum uric acid levels with risk of gestational diabetes and birth outcomes: a retrospective cohort study
Authors: Pang Ting-Ting , Zhou Zi-Xing , Li Peng-Sheng , Ma Hui-Ting , Shen Xiu-Yin , Wan Ying-Chun , Guo Xiao-Ling , Liu Zheng-Ping , Chen Geng-Dong
Published: November 2023

Background

Previous evidence suggests that higher blood uric acid (UA) levels are associated with adverse cardiovascular outcomes during pregnancy and subsequent birth outcomes. However, it has been relatively unclear whether these associations persist in normotensive pregnant women.

Methods

The study was based on a retrospective analysis of 18,250 mother-infant pairs in a large obstetric center in China. Serum UA concentrations in early pregnancy (median: 17.6, IQR: 16.3, 18.6 gestational weeks) were assessed. Hyperuricemia was defined as ≥ one standard deviation (SD) of the reference value for the corresponding gestational age. Outcomes of gestational diabetes mellitus (GDM), preterm birth (PB), low birth weight (LBW), macrosomia, small for gestational age (SGA) and large for gestational age (LGA) were extracted from the medical records.

Results

The mean maternal UA level was 0.22 ± 0.05 mmol/L, and 2,896 (15.9%) subjects had hyperuricemia. After adjustment for several covariates, UA was associated with several adverse outcomes. The ORs (95%CI) per one SD increase in serum UA concentration were 1.250 (1.136, 1.277) for GDM, 1.137 (1.060, 1.221) for PB, 1.134 (1.051, 1.223) for LBW, and 1.077 (1.020, 1.137) for SGA, respectively. Similar adverse associations were found between hyperuricemia and GDM, PB (ORs: 1.394 and 1.385, P < 0.001), but not for LBW, macrosomia, SGA, and LGA. Adverse associations tended to be more pronounced in subjects with higher BMI for outcomes including PB, LBW, and SGA (P interaction = 0.001–0.028).

Conclusion

Higher UA levels in early pregnancy were associated with higher risk of GDM, PB, LBW, and SGA in normotensive Chinese women.
Effect of arginine-fluoride varnish on preventing enamel erosion by paediatric liquid medicaments
Authors: Yip Kimberley , Abdalla Mohamed Mahmoud , Bijle Mohammed Nadeem , Yiu Cynthia
Published: November 2023

Background

The study objective was to examine the effect of arginine-sodium fluoride (Arg-NaF) varnish on preventing enamel erosion by acidic paediatric liquid medicaments (PLM).

Methods

The treatment groups were: 1) 2% Arg-NaF; 2) 4% Arg-NaF; 3) 8% Arg-NaF; 4) NaF; 5) MI (CPP-ACFP) varnishes; and 6) no varnish. The pH of PLM (paracetamol and chlorpheniramine) was measured at baseline and after immersing the Perspex® blocks coated with varnishes at 0 min, 30 min, 1 h, and 4 h. Seventy-two enamel specimens (n = 72) were randomly divided into 2 groups by PLM and further by treatment groups. Then, the specimens were pre-treated with varnishes and subjected to erosive cycles (5 min, 2×/day for 4 days) by PLM. After each erosive challenge, the specimens were stored in artificial saliva. At baseline and after 4 days, the specimens were assessed for surface roughness (Ra) using 2D-surface profilometric analysis (SPA) and atomic force microscopy (AFM). Additionally, the Ca/P ratio was determined using scanning electron microscopy with energy-dispersive X-ray spectroscopy. Paired samples dependent t-test, 1-way ANOVA and 2-way ANOVA with Bonferroni post-hoc tests were used to analyse data with the level of significance set at p < 0.05.

Results

The pH of PLM with 8% Arg-NaF was significantly higher than the other groups at 30 min and 4 h (p < 0.05). With paracetamol, no significant difference was observed between the baseline and post-erosive cycle measured enamel Ra (by SPA/AFM) and Ca/P ratio for all treatment groups (p > 0.05). The Ra determined by AFM, at the post-erosive cycle with chlorpheniramine, when treated with 4 and 8% Arg-NaF was significantly lower than the other groups (p < 0.05); except CPP-ACFP (p > 0.05). With the chlorpheniramine post-erosive cycle, the Ca/P ratio for 4, 8% Arg-NaF and CPP-ACFP treated specimens was significantly higher than the baseline Ca/P (p < 0.05).

Conclusion

The 4%/8% Arg-NaF and MI varnish® application exhibit an enhanced preventive effect against low pH (pH < 3.0) PLM-mediated enamel erosive challenges compared to 5% NaF varnish.
Curettage combined with bone cavity opening reduces recurrence of the mandibular conventional ameloblastoma and effectively preserves the mandible: a retrospective study
Authors: Zhang Yuan , Xing Aili , He Jingya , Wang Feng , Li Zhongrui , Sun Bin
Published: November 2023

Background

Patients with mandibular conventional ameloblastoma undergoing radical surgical treatment experience greater trauma and often find it challenging to accept, whereas conservative therapy is associated with a higher recurrence rate. In this study, we have improved traditional conservative treatment for mandibular conventional ameloblastoma by curettage combined with bone cavity opening (Cur/BCO). This retrospective study aimed to evaluate the effectiveness of the Cur/BCO treatment by comparing its recurrence rate and bone mineral density (BMD) growth rate with the traditional conservative treatment approach.

Methods

A total of 40 patients, meeting the study’s inclusion and exclusion criteria from 2012 to 2020, were screened, with 20 in the modified group and 20 in the traditional group. ImageJ (RRID: SCR_003070) software was employed for measuring image indices. All data were analyzed using T-test, Chi-square test and Fisher exact test in SPSS 26.0 (p = 0.05).

Results

The incidence of recurrence was significantly lower in the modified group, at only 5%, compared to 35% in the traditional group (p < 0.05). Regarding bone mineral density (BMD) growth rate, the average value in the modified group was 0.0862 ± 0.2302 (/month), significantly higher than the average value of 0.0608 ± 0.2474 (/month) in the traditional group (p < 0.05).

Conclusions

In this study, it was found that the recurrence rate of the modified conservative treatment (Cur/BCO) was lower than that of the traditional conservative treatment for managing mandibular conventional ameloblastoma. Furthermore, the BMD growth rate was quicker in the modified group. Thus, Cur/BCO could be considered as a viable option for the conservative treatment of mandibular conventional ameloblastoma.
The responsibility to quench thirst by providing drinks when a relative is dying spouses’ experience in specialist palliative home care
Authors: Friedrichsen Maria , Waldréus Nana , Milovanovic Micha , Schaller Anne Söderlund , Jaarsma Pier , Jaarsma Tiny
Published: November 2023

Background

Thirst and dry mouth are common symptoms in terminally ill patients. It is known that family members usually request drips for their dying relative. Few studies have focused on thirst in terminally ill patients and their spouses’ experience of this, leading to a knowledge gap in this area.

Aim

The aim of this study was to explore spouses’ experiences of observing and managing thirst in a dying relative admitted to specialist palliative home care.

Methods

A qualitative interview study with an inductive approach was conducted. Eighteen spouses caring for their husband or wife admitted to specialist palliative home care in different hospitals in Sweden were interviewed. The interviews were transcribed verbatim and analysed with a reflexive thematic analysis.

Results

Three main themes emerged regarding spouses’ experiences of patients’ thirst: Knowledge and views of thirst; Control of fluid intake provides vital information; and Taking charge of their drinking is a life and death responsibility.

Conclusions

Spouses experience a responsibility to serve the dying person with fluids so that they will not get thirsty. It is so obvious and commonplace to them. To be able to fulfil this responsibility, they need to keep track of the patient’s fluid intake and know what quenches thirst. There is a need for research in this area to assist carers and patients in identifying which drinks best quench the patient’s thirst. Interventions are also needed to help provide/make available knowledge on suitable thirst-quenching drinks.
Tracking the effect of roasting and fermentation on the metabolites of licorice root (Glycyrrhiza glabra L.) using UPLC-MS analysis combined with multivariate statistical analysis
Authors: Takla Sarah S. , Shawky Eman , Mahgoub Yasmin A. , Darwish Reham S.
Published: November 2023

Background

Roasting, honey-roasting and fermentation are the most common pre-processing procedures of licorice roots. They were shown to noticeably change the composition of extracts. In this work, the common alterations in licorice secondary metabolites by processing were interpreted. Comprehensive metabolic profiling of different studied samples was undergone.

Methods

UPLC-QqQ-MS/MS analysis coupled to various chemometric analysis models was implemented to unravel the effect of different pre-processing procedures on the chemical profile of licorice samples.

Results

UPLC-QqQ-MS/MS analysis designated 133 chromatographic peaks with saponins, flavonoids, chalcones and pterocarpans being the most abundant groups. Triterpene saponins dominated the secondary metabolites in the aqueous extracts, with fermented samples showing the highest relative amounts. Meanwhile the ethanol extracts showed significant amounts of chalcones. Melanoidins were only detected in roasted and honey roasted samples. Multivariate models indicated that roasting of samples induced a greater effect on the polar metabolites rather than nonpolar ones. Variable of importance (VIP) plot indicated that glycyrrhizin and its hydrolysis product glycyrrhetinic acid, trihdroxychalcone diglycoside, glabrone and glabridin are the main chemical features responsible for the discrimination of samples.

Conclusion

Coupling UPLC-MS/MS to multivariate analysis was a successful tool that unveiled the significant effect of different pre-processing methods on the chemical profile of processed and unprocessed licorice samples. Moreover, such coupling unraveled the discriminatory chemical compounds among tested samples that can be employed as markers for the processing procedure of licorice.
Comparing associations of handgrip strength and chair stand performance with all-cause mortality—implications for defining probable sarcopenia: the Tromsø Study 2015–2020
Authors: Johansson Jonas , Grimsgaard Sameline , Strand Bjørn Heine , Sayer Avan A. , Cooper Rachel
Published: November 2023

Background

Widely adopted criteria suggest using either low handgrip strength or poor chair stand performance to identify probable sarcopenia. However, there are limited direct comparisons of these measures in relation to important clinical endpoints. We aimed to compare associations between these two measures of probable sarcopenia and all-cause mortality.

Methods

Analyses included 7838 community-dwelling participants (55% women) aged 40–84 years from the seventh survey of the Tromsø Study (2015–2016), with handgrip strength assessed using a Jamar + Digital Dynamometer and a five-repetition chair stand test (5-CST) also undertaken. We generated sex-specific T-scores and categorised these as “not low”, “low”, and “very low” handgrip strength or 5-CST performance. Cox Proportional Hazard regression models were used to investigate associations between these two categorised performance scores and time to death (up to November 2020 ascertained from the Norwegian Cause of Death registry), adjusted for potential confounders including lifestyle factors and specific diseases.

Results

A total of 233 deaths occurred (median follow-up 4.7 years) with 1- and 5-year mortality rates at 3.1 (95% confidence interval [CI] 2.1, 4.6) and 6.3 (95% CI 5.5, 7.2) per 1000 person-years, respectively. There was poor agreement between the handgrip strength and 5-CST categories for men (Cohen’s kappa [κ] = 0.19) or women (κ = 0.20). Fully adjusted models including handgrip strength and 5-CST performance mutually adjusted for each other, showed higher mortality rates among participants with low (hazard ratio [HR] 1.22, 95% CI 0.87, 1.71) and very low (HR 1.68, 95% CI 1.02, 2.75) handgrip strength compared with the not low category. Similar associations, although stronger, were seen for low (HR 1.88, 95% CI 1.38, 2.56) and very low (HR 2.64, 95% CI 1.73, 4.03) 5-CST performance compared with the not low category.

Conclusions

We found poor agreement between T-score categories for handgrip strength and 5-CST performance and independent associations with mortality. Our findings suggest that these tests identify different people at risk when case-finding probable sarcopenia. As discussions on an international consensus for sarcopenia definitions proceed, testing both handgrip strength and chair stand performance should be recommended rather than viewing these as interchangeable assessments.
Association of MMP3, MMP14, and MMP25 gene polymorphisms with cerebral stroke risk: a case-control study
Authors: Yin Yanling , Zhang Yu , Zhang Xiaobo , Zhang Qi , Wang Jiachen , Yang Tian , Liang Chen , Li Wu , Liu Jie , Ma Xiaojuan , Duan Jinwei , Shi Wenzhen , Tian Ye
Published: November 2023

Background

Cerebral stroke (CS) is the leading cause of death in China, and a complex disease caused by both alterable risk factors and genetic factors. This study intended to investigate the association of MMP3, MMP14, and MMP25 single nucleotide polymorphisms (SNPs) with CS risk in a Chinese Han population.

Methods

A total of 1,348 Han Chinese were recruited in this case-control study. Four candidate loci including rs520540 A/G and rs679620 T/C of MMP3, rs2236302 G/C of MMP14, and rs10431961 T/C of MMP25 were successfully screened. The correlation between the four SNPs and CS risk was assessed by logistic regression analysis. The results were analyzed by false-positive report probability (FPRP) for chance or significance. The interactions between four SNPs associated with CS risk were assessed by multifactor dimensionality reduction (MDR).

Results

rs520540 A/G and rs679620 C/T SNP in MMP3 were associated with risk of CS in allele, codominant, dominant and log-additive models. Ischemic stroke risk were significantly lower in carriers with rs520540-A allele and rs679620-T allele than those with G/G or C/C genotypes. However, rs520540-A allele and rs679620-T allele were associated with higher risk of hemorrhagic stroke. Stratified analysis showed that these two SNPs were associated with reduced risk of CS in aged < 55 years, non-smoking and non-drinking participants, and rs679620 SNP also reduced CS risk in male participants. The levels of uric acid, high-density lipoprotein cholesterol, and eosinophil were different among patients with different genotypes of rs520540 and rs679620. No statistically significant association was found between MMP14 rs2236302 G/C or MMP25 rs10431961 T/C with CS even after stratification by stroke subtypes, age, gender as well as smoking and drinking conditions in all the genetic models.

Conclusion

MMP3 rs520540 A/G and rs679620 C/T polymorphisms were associated with CS risk in the Chinese Han population, which provides useful information for the prevention and diagnosis of CS.
Impact of sex differences on cardiac injury in critically ill patients with COVID-19
Authors: Jozwiak Mathieu , Doyen Denis , Denormandie Pierre , Goury Antoine , Marey Jonathan , Pène Frédéric , Cariou Alain , Mira Jean-Paul , Dellamonica Jean , Nguyen Lee S.
Published: November 2023

Background

COVID-19 infections are associated with accrued inflammatory responses which may result in cardiac injury. Immune response to infection appears different between men and women, suggesting that COVID-19 patients’ outcomes may differ according to biological sex. However, the impact of biological sex on the occurrence of cardiac injury during intensive care unit (ICU) stay in COVID-19 patients remain unclear.

Methods

In this multicenter and prospective study, we included consecutive patients admitted to ICU for severe COVID-19 pneumonia, during the first two pandemic waves. Biological, electrocardiogram (ECG) and echocardiographic variables were collected on ICU admission. Cardiac injury was defined by increased troponin above 99th percentile of upper norm value and newly diagnosed ECG and/or echocardiographic abnormalities. The primary endpoint was the proportion of patients with cardiac injury during ICU stay according to biological sex. The impact of biological sex on other subsequent clinical outcomes was also evaluated.

Results

We included 198 patients with a median age of 66 (56–73) years, 147 (74%) patients were men and 51 (26%) were women. Overall, 119 (60%) patients had cardiac injury during ICU stay and the proportion of patients with cardiac injury during ICU stay was not different between men and women (60% vs. 61%, p = 1.00). Patients with cardiac injury during ICU stay showed more cardiovascular risk factors and chronic cardiac disease and had a higher ICU mortality rate. On ICU admission, they had a more marked lymphopenia (0.70 (0.40–0.80) vs. 0.80 (0.50–1.10) × 109/L, p < 0.01) and inflammation (C-Reactive Protein (155 (88–246) vs. 111 (62–192) mg/L, p = 0.03); D-Dimers (1293 (709–2523) vs. 900 (560–1813) µg/L, p = 0.03)). Plasmatic levels of inflammatory biomarkers on ICU admission correlated with SAPS-2 and SOFA scores but not with the different echocardiographic variables. Multivariate analysis confirmed cardiovascular risk factors (OR = 2.31; 95%CI (1.06–5.02), p = 0.03) and chronic cardiac disease (OR = 8.58; 95%CI (1.01–73.17), p = 0.04) were independently associated with the occurrence of cardiac injury during ICU stay, whereas biological sex (OR = 0.88; 95%CI (0.42–1.84), p = 0.73) was not. Biological sex had no impact on the occurrence during ICU stay of other clinical outcomes.

Conclusions

Most critically ill patients with COVID-19 were men and experienced cardiac injury during ICU stay. Nevertheless, biological sex had no impact on the occurrence of cardiac injury during ICU stay or on other clinical outcomes.

Clinical trial registration NCT04335162
Optimization of trans-4-hydroxyproline synthesis pathway by rearrangement center carbon metabolism in Escherichia coli
Authors: Gong Yu , Wang Ruiqi , Ma Ling , Wang Shuo , Li Changgeng , Xu Qingyang
Published: November 2023

Background

trans-4-Hydroxyproline (T-4-HYP) is a promising intermediate in the synthesis of antibiotic drugs. However, its industrial production remains challenging due to the low production efficiency of T-4-HYP. This study focused on designing the key nodes of anabolic pathway to enhance carbon flux and minimize carbon loss, thereby maximizing the production potential of microbial cell factories.

Results

First, a basic strain, HYP-1, was developed by releasing feedback inhibitors and expressing heterologous genes for the production of trans-4-hydroxyproline. Subsequently, the biosynthetic pathway was strengthened while branching pathways were disrupted, resulting in increased metabolic flow of α-ketoglutarate in the Tricarboxylic acid cycle. The introduction of the NOG (non-oxidative glycolysis) pathway rearranged the central carbon metabolism, redirecting glucose towards acetyl-CoA. Furthermore, the supply of NADPH was enhanced to improve the acid production capacity of the strain. Finally, the fermentation process of T-4-HYP was optimized using a continuous feeding method. The rate of sugar supplementation controlled the dissolved oxygen concentrations during fermentation, and Fe2+ was continuously fed to supplement the reduced iron for hydroxylation. These modifications ensured an effective supply of proline hydroxylase cofactors (O2 and Fe2+), enabling efficient production of T-4-HYP in the microbial cell factory system. The strain HYP-10 produced 89.4 g/L of T-4-HYP in a 5 L fermenter, with a total yield of 0.34 g/g, the highest values reported by microbial fermentation, the yield increased by 63.1% compared with the highest existing reported yield.

Conclusion

This study presents a strategy for establishing a microbial cell factory capable of producing T-4-HYP at high levels, making it suitable for large-scale industrial production. Additionally, this study provides valuable insights into regulating synthesis of other compounds with α-ketoglutaric acid as precursor.
Caregiver acceptance of malaria vaccination for children under 5 years of age and associated factors: cross-sectional household survey, Guinea and Sierra Leone, 2022
Authors: Röbl Klara , Fischer Hanna-Tina , Delamou Alexandre , Mbawah Abdul Karim , Geurts Brogan , Feddern Lukas , Baldé Habibata , Kaba Ibrahima , Pozo-Martin Francisco , Weishaar Heide , Menelik-Obbarius Sara , Burger Gerrit , Diaconu Viorela , Dörre Achim , El Bcheraoui Charbel
Published: November 2023

Background

Malaria is a leading cause of death and reduced life span in Guinea and Sierra Leone, where plans for rolling out the malaria vaccine for children are being made. There is little evidence about caregiver acceptance rates to guide roll-out policies. To inform future vaccine implementation planning, this analysis aimed to assess potential malaria vaccine acceptance by caregivers and identify factors associated with acceptance in Guinea and Sierra Leone.

Methods

A cross-sectional household survey using lot quality assurance sampling was conducted in three regions per country between May 2022 and August 2022. The first survey respondent in each household provided sociodemographic information. A household member responsible for childcare shared their likelihood of accepting a malaria vaccine for their children under 5 years and details about children’s health. The prevalence of caregiver vaccine acceptance was calculated and associated factors were explored using multivariable logistic regression modelling calculating adjusted odds ratios (aOR) with 95% confidence intervals (CI).

Results

Caregivers in 76% of 702 sampled households in Guinea and 81% of 575 households in Sierra Leone were accepting of a potential vaccine for their children. In both countries, acceptance was lower in remote areas than in urban areas (Guinea: aOR 0.22 [95%CI 0.09–0.50], Sierra Leone: 0.17 [0.06–0.47]). In Guinea, acceptance was lower among caregivers living in the richest households compared to the poorest households (0.10 [0.04–0.24]), among those whose children were tested for malaria when febrile (0.54 [0.34–0.85]) and in households adopting more preventative measures against malaria (0.39 [0.25–0.62]). Better knowledge of the cause of malaria infection was associated with increased acceptance (3.46 [1.01–11.87]). In Sierra Leone, vaccine acceptance was higher among caregivers living in households where the first respondent had higher levels of education as compared to lower levels (2.32 [1.05–5.11]).

Conclusion

In both countries, malaria vaccine acceptance seems promising for future vaccine roll-out programmes. Policy makers might consider regional differences, sociodemographic factors, and levels of knowledge about malaria for optimization of implementation strategies. Raising awareness about the benefits of comprehensive malaria control efforts, including vaccination and other preventive measures, requires attention in upcoming campaigns.
Does the ketogenic diet improve neurological disorders by influencing gut microbiota? A systematic review
Authors: Mazandarani Mahdi , Lashkarbolouk Narges , Ejtahed Hanieh-Sadat , Qorbani Mostafa
Published: November 2023

Background

The aim of this systematic review is to evaluate the changes in gut microbiota (GM) induced by the Ketogenic Diets (KD) as a potential underlying mechanism in the improvement of neurological diseases.

Methods

A comprehensive search was conducted on three electronic databases, including PubMed/Medline, Web of Science, and Scopus until December 2022. The inclusion criteria were studies that described any changes in GM after consuming KD in neurological patients. Full text of studies such as clinical trials and cohorts were added. The quality assessment of cohort studies was conducted using the Newcastle–Ottawa Quality Assessment Scale and for the clinical trials using the Cochrane Collaboration tool. The search, screening, and data extraction were performed by two researchers independently.

Results

Thirteen studies examining the effects of the KD on the GM in neurological patients were included. Studies have shown that KD improves clinical outcomes by reducing disease severity and recurrence rates. An increase in Proteobacteria phylum, Escherichia, Bacteroides, Prevotella, Faecalibacterium, Lachnospira, Agaricus, and Mrakia genera and a reduction in Firmicutes, and Actinobacteria phyla, Eubacterium, Cronobacter, Saccharomyces, Claviceps, Akkermansia and Dialister genera were reported after KD. Studies showed a reduction in concentrations of fecal short-chain fatty acids and branched-chain fatty acids and an increase in beta Hydroxybutyrate, trimethylamine N-oxide, and N-acetylserotonin levels after KD.

Conclusion

The KD prescribed in neurological patients has effectively altered the GM composition and GM-derived metabolites.
IL-1β mediates the induction of immune checkpoint regulators IDO1 and PD-L1 in lung adenocarcinoma cells
Authors: Nawas Afshan Fathima , Solmonson Ashley , Gao Boning , DeBerardinis Ralph J. , Minna John D. , Conacci-Sorrell Maralice , Mendelson Carole R.
Published: November 2023

Introduction

Inflammation plays a significant role in various cancers, including lung cancer, where the inflammatory cytokine IL-1β is often elevated in the tumor microenvironment. Patients with lung adenocarcinoma show higher levels of serum IL-1β compared to healthy individual. Moreover, IL-1β blockade reduces the incidence and mortality of lung cancer. Our prior studies revealed that alveolar type-II cells, the precursors for lung adenocarcinoma, display an induction in the expression of the enzyme tryptophan 2,3-dioxygenase (TDO2) during normal lung development. This induction of TDO2 coincides with an increase in IL-1β levels and is likely caused by IL-1β. Given that cancer cells can co-opt developmentally regulated pathways, we hypothesized that IL-1β may exert its pro-tumoral function by stimulating TDO2 and indoleamine 2, 3-dioxygenase-1 (IDO1), parallel enzymes involved in the conversion of tryptophan (Trp) into the immune-suppressive oncometabolite kynurenine (Kyn). Our goal was to determine whether IL-1β is a common upstream regulator of immune checkpoint regulators.

Methods

To determine whether IL-1β regulates IDO1, TDO2, PD-L1, and PD-L2, we measured mRNA and protein levels in lung adenocarcinoma cells lines (A549, H1792, H1838, H2347, H2228, HCC364 and HCC827) grown in 2D or 3D and in immortalized normal lung epithelial cells (HBEC3-KT and HSAEC1-KT). To determine the importance of the NFκB pathway in mediating IL-1β -regulated cellular effects, we used siRNA to knockdown RelA/p65 in IL-1β treated cells. The levels of Trp and Kyn in the IL-1β-treated cells and media were measured by mass spectrometry.

Results

Upon IL-1β stimulation, lung adenocarcinoma cells exhibited significant increases in IDO1 mRNA and protein levels, a response that depended on the NFκB pathway. Interestingly, this induction was more pronounced in 3D spheroid cultures compared to monolayer cultures and was not observed in normal immortalized lung epithelial cells. Furthermore, the conversion of Trp to Kyn increased in cells exposed to IL-1β, aligning with the heightened IDO1 expression. Remarkably, IL-1β also upregulated the expression of programmed death ligand-1 (PD-L1) and PD-L2 in multiple cell lines, indicating that IL-1β triggers parallel immune-suppressive mechanisms in lung adenocarcinoma cells.

Conclusions

Our studies demonstrate that lung adenocarcinoma cells, but not normal immortalized lung epithelial cells, respond to IL-1β signaling by inducing the expression of parallel immune checkpoint proteins that have the potential to promote immune evasion.
Sex differences in the association between plasma polyunsaturated fatty acids levels and moderate-to-severe plaque psoriasis severity: a cross-sectional and longitudinal study
Authors: Wang Xin , Ma Rui , Shi Rongcan , Qin Hui , Chen Wenjuan , Yu Zengyang , Ding Yangfeng , Peng Chen , Shi Yuling
Published: November 2023

Background

Psoriasis is a chronic inflammatory skin disease with metabolic abnormalities serving as important contributors for pathogenesis and progression. Polyunsaturated fatty acids (PUFAs) have been found to be associated with human diseases, including psoriasis. However, differences and controversies exist regarding their content and roles.

Methods

Plasma PUFAs concentrations were measured in 296 patients with moderate-to-severe plaque psoriasis from the Shanghai Psoriasis Effectiveness Evaluation CoHort. Disease severity was assessed using Clinician-Reported Outcomes (ClinROs), including Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) and Physician Global Assessment (PGA), as well as Patient-Reported Outcomes (PROs), including Patient Global Assessment (PtGA) and Dermatology Life Quality Index (DLQI). Multivariate generalized linear regression models (GLMs), subgroup and interaction analysis, and restricted cubic spline were used to estimate the cross-sectional associations between PUFAs concentrations and disease severity. Longitudinal assessments of PASI scores and PASI response were conducted at a 12-week follow-up. Associations between baseline plasma PUFAs levels and prospective PASI scores or PASI response were assessed using multivariate GLMs or logistic regression models.

Results

Males suffered severer psoriasis and presented lower plasma docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels compared to females. Among males, plasma eicosadienoic acid (EDA) level was positively associated with PASI, BSA and PGA scores, while total Omega-3 PUFAs and/or eicosapentaenoic acid (EPA) levels exhibited non-linear associations with PASI and/or BSA scores. α-Linolenic acid (ALA) was negatively, whereas ARA was positively, associated with DLQI scores. In females, Omega-3 PUFAs, including EPA, DHA, and total Omega-3 PUFAs, showed inverse associations with PASI and BSA scores. Longitudinally, plasma total Omega-6 PUFAs were positively associated with the likelihood of achieving PASI 100 at 12 weeks in males. In females, concentrations of dohomo-γ-linolenic acid were prospectively associated with an increase in PASI scores, and DHA was associated with the likelihood of achieving PASI 75 and PASI 90 decline.

Conclusions

Sex differences cross-sectionally exist in disease severity and plasma PUFAs levels. The association between PUFAs and psoriasis severity also varies cross-sectionally and longitudinally between males and females. Sex differences should be considered when studying the function and clinical application of PUFAs in psoriasis.