bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of potential molecular targets for the treatment of cluster 1 human pheochromocytoma and paraganglioma via comprehensive proteomic characterization
Authors: Vit Ondrej , Talacko Pavel , Musil Zdenek , Hartmann Igor , Pacak Karel , Petrak Jiri
Published: September 2023

Background

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors. New drug targets and proteins that would assist sensitive PPGL imagining could improve therapy and quality of life of patients with PPGL, namely those with recurrent or metastatic disease. Using a combined proteomic strategy, we looked for such clinically relevant targets among integral membrane proteins (IMPs) upregulated on the surface of tumor cells and non-membrane druggable enzymes in PPGL.

Methods

We conducted a detailed proteomic analysis of 22 well-characterized human PPGL samples and normal chromaffin tissue from adrenal medulla. A standard quantitative proteomic analysis of tumor lysate, which provides information largely on non-membrane proteins, was accompanied by specific membrane proteome-aimed methods, namely glycopeptide enrichment using lectin-affinity, glycopeptide capture by hydrazide chemistry, and enrichment of membrane-embedded hydrophobic transmembrane segments.

Results

The study identified 67 cell surface integral membrane proteins strongly upregulated in PPGL compared to control chromaffin tissue. We prioritized the proteins based on their already documented direct role in cancer cell growth or progression. Increased expression of the seven most promising drug targets (CD146, CD171, ANO1, CD39, ATP8A1, ACE and SLC7A1) were confirmed using specific antibodies. Our experimental strategy also provided expression data for soluble proteins. Among the druggable non-membrane enzymes upregulated in PPGL, we identified three potential drug targets (SHMT2, ARG2 and autotaxin) and verified their upregulated expression.

Conclusions

Application of a combined proteomic strategy recently presented as “Pitchfork” enabled quantitative analysis of both, membrane and non-membrane proteome, and resulted in identification of 10 potential drug targets in human PPGL. Seven membrane proteins localized on the cell surface and three non-membrane druggable enzymes proteins were identified and verified as significantly upregulated in PPGL. All the proteins have been previously shown to be upregulated in several human cancers, and play direct role in cancer progression. Marked upregulation of these proteins along with their localization and established direct roles in tumor progression make these molecules promising candidates as drug targets or proteins for sensitive PPGL imaging.
Convergent TP53 loss and evolvability in cancer
Authors: Mansur Marcela Braga , Greaves Mel
Published: September 2023

Cancer cell populations evolve by a stepwise process involving natural selection of the fittest variants within a tissue ecosystem context and as modified by therapy. Genomic scrutiny of patient samples reveals an extraordinary diversity of mutational profiles both between patients with similar cancers and within the cancer cell population of individual patients. Does this signify highly divergent evolutionary trajectories or are there repetitive and predictable patterns?

Major evolutionary innovations or adaptations in different species are frequently repeated, or convergent, reflecting both common selective pressures and constraints on optimal solutions. We argue this is true of evolving cancer cells, especially with respect to the TP53 gene. Functional loss variants in TP53 are the most common genetic change in cancer. We discuss the likely microenvironmental selective pressures involved and the profound impact this has on cell fitness, evolvability and probability of subsequent drug resistance.
Typical metabolic pattern of 18F-FDG PET in Anti-NMDAR encephalitis in the acute and subacute phases and its correlation with T2 FLAIR-MRI features
Authors: Yuan Leilei , Mao Guangjuan , Zhang Yudi , Xu Yang , Chen Qian , Shan Baoci , Cui Tao , Ai Lin
Published: September 2023

Background/aims

Early diagnosis of Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis with non-invasive imaging modalities benefiting is crucial to guarantee prompt treatments decision-making and good prognosis for patients. The present study aimed to explore the correlation of MRI features with brain metabolism characteristics of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) and to describe the metabolic patterns in Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis at acute and subacute phases. Twenty-four patients with anti-NMDAR encephalitis confirmed by serum and/or CSF tests at acute and subacute phases, 9 females and 15 males, with an age range of 6–80 years, were enrolled in this retrospective study as encephalitis group. 18F-FDG PET and MRI findings of all patients were investigated and interpreted with visual analysis. Chi-square test was performed to compare the diagnostic sensitivity between MRI and PET. Independent sample t-test was used to compare the standardized uptake value ratio (SUVR) of each ROI between the encephalitis group and control group, which consisted of 24 healthy volunteers of the same age and gender.

Results

There was no statistical difference in the diagnostic sensitivity between FDG PET (23/24, 95.83%) and MRI (18/24, 75.00%) in anti-NMDAR encephalitis patients (P > 0.05). Three categories of abnormalities shown on T2 FLAIR, including shallow of sulci and swelling of brain tissue, increased signal in the sulci, increased signal on brain gray matter or adjacent white matter presented hypermetabolism on PET, excepting increased signal in brain linear structure with hypometabolism of the basal ganglia on PET. We identified 19 brain regions with hypermetabolism and 16 brain regions with hypometabolism that exhibited statistically significant changes in SUVRs between anti-NMDAR encephalitis group and control group (FDR P < 0.05).

Conclusion

Anteroposterior glucose metabolism gradient (frontal-temporal/parietal-occipital) is proved to be a typical pattern of anti-NMDAR encephalitis at the acute and subacute phases in both visual and statistical testing. Interestingly, the pattern is also commonly found in the anterior and posterior portions of the parietal lobe and cingular cortex, which may be a potential indicator for the diagnosis of this disorder. In addition, MRI is an important and reliable neuroimaging modality to assist in the correct evaluation of activity changes on individual 18F-FDG PET.
Exploring root system architecture and anatomical variability in alfalfa (Medicago sativa L.) seedlings
Authors: Pan Xinya , Wang Pengfei , Wei Xianwei , Zhang Jinxin , Xu Bingcheng , Chen Yinglong , Wei Gehong , Wang Zhi
Published: September 2023

Background

The growth of alfalfa (Medicago sativa L.) is significantly hampered by drought and nutrient deficiencies. The identification of root architectural and anatomical characteristics holds paramount importance for the development of alfalfa genotypes with enhanced adaptation to adverse environmental conditions. In this study, we employed a visual rhizobox system to investigate the variability in root system architecture (including root depth, root length, root tips number, etc.), anatomical features (such as cortical traits, total stele area, number and area of vessel, etc.), as well as nitrogen and phosphorus uptake across 53 alfalfa genotypes during the seedling stage.

Results

Out of the 42 traits measured, 21 root traits, along with nitrogen (N) and phosphorus (P) uptake, displayed higher coefficients of variation (CVs ≥ 0.25) among the tested genotypes. Local root morphological and anatomical traits exhibited more significant variation than global root traits. Twenty-three traits with CVs ≥ 0.25 constituted to six principal components (eigenvalues > 1), collectively accounting for 88.0% of the overall genotypic variation. Traits such as total root length, number of root tips, maximal root depth, and others exhibited positive correlations with shoot dry mass and root dry mass. Additionally, total stele area and xylem vessel area showed positive correlations with N and P uptake.

Conclusions

These root traits, which have demonstrated associations with biomass and nutrient uptake, may be considered for the breeding of alfalfa genotypes that possess efficient resource absorption and increased adaptability to abiotic stress, following validation during the entire growth period in the field.
Comparison of the efficacy and safety between rivaroxaban and dabigatran in the treatment of acute portal vein thrombosis in cirrhosis
Authors: Zhou Haonan , Wu Mingdong , Yu Shixiong , Xia Han , Yu Wu , Huang Kai , Chen Yikuan
Published: September 2023

Background

New oral anticoagulants (NOACs) have been becoming prevalent in recent years and are increasingly used in the treatment of port vein thrombosis. The difference of the efficacy and safety between rivaroxaban and dabigatran remains unclear in the treatment of cirrhotic patients with acute portal vein thrombosis (PVT).

Methods

This retrospective study included all consecutive cirrhotic patients with acute portal vein thrombosis in our institute from January 2020 to December 2021. The patients received oral anticoagulation with rivaroxaban or dabigatran. The demographic, clinical, and imaging data of patients were collected. The diagnosis of acute PVT was confirmed by imaging examinations. The severity of liver cirrhosis was assessed using Child–Pugh score and Model for End-Stage Liver Disease (MELD) score. Outcomes included recanalization (complete, partial, and persistent occlusion), liver function, bleedings, and survival. The log-rank test was used to compare Kaplan–Meier distributions of time-to-event outcomes. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).

Results

A total of 94 patients were included, 52 patients (55%) received rivaroxaban and 42 (45%) with dabigatran. The complete and partial recanalization of PVT was observed in 41 patients. There was no significant difference in complete recanalization, partial recanalization, and persistent occlusion between the two groups. With multivariate analysis, D-dimer (HR 1.165, 95% CI 1.036–1.311, p = 0.011) was independent predictors of complete recanalization. The Child–Pugh score (p = 0.001) was significantly improved in both two groups after anticoagulation, respectively. However, there was no difference between the two groups. The probability of survival was 94%, 95% in the rivaroxaban and dabigatran groups (log-rank p = 0.830). Major bleedings were reported in 3 patients (6%) in rivaroxaban group and 1 patient (2%) in dabigatran group (p = 0.646). Six patients (12%) in rivaroxaban group experienced minor bleeding, and five (12%) from dabigatran group (p = 0.691).

Conclusions

The efficacy and safety were comparable between rivaroxaban and dabigatran in the treatment of cirrhotic patients with acute portal vein thrombosis. And D-dimer can contribute to the prediction of PVT recanalization in cirrhotic patients.
A diarized journey: an interpretative phenomenological analysis of the older person’s lived experience of a hip or knee replacement within a fast-track programme
Authors: Burger Marisa , Watson Francois , van Wyk Annemarie
Published: September 2023

Background

For the older person living with end-stage hip or knee osteoarthritis, a hip or knee replacement can be a traumatic event, influencing the physical, physiological, psychological, social and economic facets of daily living. This interpretative phenomenological study aimed to reveal and interpret the daily lived experiences of the older person before, during and after a primary total hip or knee replacement surgery in a fast-track programme in South Africa.

Methods

A qualitative interpretive phenomenological study, collecting data through solicited diaries and reflexive member validation interviews from seven participants aged 65–75 years, who underwent a primary elective hip or knee replacement surgery. The surgical fast-track process and data collection process happened simultaneously. Data collection from the solicited diary started before surgery, continued during the surgery process and finished six weeks after surgery and this was followed with reflexive member validation interviews. Interpretative phenomenological analysis was used throughout the three phases of the fast-track programme.

Results

Three superordinate themes developed during the three phases of surgery: “The holistic impact of pain on daily quality of life”, “Finding ways to cope”, and “Transition between independence and dependence and back”. Although former research confirms the physical impact of osteoarthritis on the older person and the success of fast-track programmes for subsequent hip and knee replacements, this study contributes to the holistic impact of the surgery on participants’ daily lives. The diarized journey of individuals through the psychological, psychosocial, physical, professional, and spiritual experience are described and interpreted in this study.

Conclusions

Across the solicited diaries, it was clear that pain as catalyst impacted the daily activities of the individual physically, psychologically, and psychosocially. Pain was subjectively present at different intensities during all the phases of the replacement surgery, impairing mobilization and triggering roller-coaster emotions. In order to cope with physical and emotional difficulties while preparing and adjusting to the environment, participants reflected on social support, physical and professional support, and spirituality. Throughout the preparation, hospitalization and the recovery process, the transition between independence, dependence, and back to independence was significant, reinforcing the individual’s determination to recover.
Can HIV self-testing reach first-time testers? A telephone survey among self-test end users in Côte d’Ivoire, Mali, and Senegal
Authors: Kra Arsène Kouassi , Fotso Arlette Simo , N’guessan Kouassi Noël , Geoffroy Olivier , Younoussa Sidibé , Kabemba Odé Kanku , Gueye Papa Alioune , Ndeye Pauline Dama , Rouveau Nicolas , Boily Marie-Claude , Silhol Romain , d’Elbée Marc , Maheu-Giroux Mathieu , Vautier Anthony , Larmarange Joseph ,   on behalf of the ATLAS team
Published: September 2023

Background

Coverage of HIV testing remains sub-optimal in West Africa. Between 2019 and 2022, the ATLAS program distributed ~400 000 oral HIV self-tests (HIVST) in Côte d’Ivoire, Mali, and Senegal, prioritising female sex workers (FSW) and men having sex with men (MSM), and relying on secondary redistribution of HIVST to partners, peers and clients to reach individuals not tested through conventional testing. This study assesses the proportion of first-time testers among HIVST users and the associated factors.

Methods

A phone-based survey was implemented among HIVST users recruited using dedicated leaflets inviting them to anonymously call a free phone number. We collected socio-demographics, sexual behaviours, HIV testing history, HIVST use, and satisfaction with HIVST. We reported the proportion of first-time testers and computed associated factors using logistic regression.

Results

Between March and June 2021, 2 615 participants were recruited for 50 940 distributed HIVST (participation rate: 5.1%). Among participants, 30% received their HIVST kit through secondary distribution (from a friend, sexual partner, family member, or colleague).

The proportion who had never tested for HIV before HIVST (first-time testers) was 41%. The main factors associated with being a first-time tester were sex, age group, education level, condom use, and secondary distribution. A higher proportion was observed among those aged 24 years or less (55% vs 32% for 25–34, aOR: 0.37 [95%CI: 0.30–0.44], and 26% for 35 years or more, aOR: 0.28 [0.21–0.37]); those less educated (48% for none/primary education vs 45% for secondary education, aOR: 0.60 [0.47–0.77], and 29% for higher education, aOR: 0.33 [0.25–0.44]). A lower proportion was observed among women (37% vs 43%, aOR: 0.49 [0.40–0.60]); those reporting always using a condom over the last year (36% vs 51% for those reporting never using them, aOR: 2.02 [1.59–2.56]); and those who received their HISVST kit through primary distribution (39% vs 46% for secondary distribution, aOR: 1.32 [1.08–1.60]).

Conclusion

ATLAS HIVST strategy, including secondary distribution, successfully reached a significant proportion of first-time testers. HIVST has the potential to reach underserved populations and contribute to the expansion of HIV testing services in West Africa.
Preoperative fistula diagnostics in male anorectal malformations after colostomy: a single-center experience
Authors: Bai Jianxi , Zhang Bing , Lin Kaiwu
Published: September 2023

Background

Accurate preoperative fistula diagnostics in male anorectal malformations (ARM) after colostomy are of great significance. We reviewed our institutional experiences and explored methods for improving the preoperative diagnostic accuracy of fistulas in males with ARMs after colostomy.

Methods

A retrospective analysis was performed on males with ARMs after colostomy admitted to our hospital from January 2015 to June 2022. All patients underwent magnetic resonance imaging (MRI) and high-pressure colostogram (HPC) before anorectal reconstruction. Patients with no fistula as diagnosed by both modalities underwent a voiding cystourethrogram (VCUG). General information, imaging results and surgical results were recorded.

Results

Sixty-nine males with ARMs after colostomy were included. Age at the time of examination was 52 ~ 213 days, and the median age was 89 days. The Krickenbeck classification according to surgical results included rectovesical fistula (n = 19), rectoprostatic fistula (n = 24), rectobulbar fistula (n = 19) and no fistula (n = 7). There was no significant difference in the diagnostic accuracy between MRI and HPC for different types of ARMs. For determining the location of the fistula, compared to surgery, HPC (76.8%, 53/69) performed significantly better than MRI (60.9%, 42/69) (p = 0.043). Sixteen patients diagnosed as having no fistula by MRI or HPC underwent a VCUG, and in 14 patients, the results were comfirmed. However, there were 2 cases of rectoprostatic fistula that were not correctly diagnosed.

Conclusion

High-pressure colostogram has greater accuracy than MRI in the diagnosis of fistula type in males with ARMs after colostomy. For patients diagnosed with no fistula by both methods, VCUG reduces the risk of false-negative exclusion, and rectoprostatic fistula should be considered during the operation.
START – physical exercise and person-centred cognitive skills training as treatment for adult ADHD: protocol for a randomized controlled trial
Authors: Lindvall Mialinn Arvidsson , Holmqvist Kajsa Lidström , Svedell Lena Axelsson , Philipson Anna , Cao Yang , Msghina Mussie
Published: September 2023

Background

Core symptoms in attention deficit hyperactivity disorder (ADHD) are inattention, impulsivity and hyperactivity. Many individuals with this disorder also have a sedentary lifestyle, co-morbid mental illness such as depressive and anxiety disorders, and reduced quality of life. People with ADHD often have impaired executive function, which among other things may include difficulty in time management and structuring of everyday life. Pharmacological treatment is often the first-line option, but non-pharmacological treatment is also available and is used in clinical settings. In children and adolescents with ADHD, physical exercise is used as a non-pharmacological treatment. However, the evidence for the effectiveness of exercise in adults is sparse.

Objective

To implement the START intervention (START = Stöd i Aktivitet, Rörelse och Träning [Support in activity, movement and exercise]) consisting of a 12-week, structured mixed exercise programme with or without a cognitive intervention, in adults with ADHD, and study whether it has an effect on core symptoms of ADHD as well as physical, cognitive, mental and everyday functioning compared with usual treatment. A secondary aim is to investigate the participants’ experiences of the intervention and its possible benefits, and to evaluate the cost-effectiveness of START compared with usual treatment.

Methods

This is a randomized controlled trial planned to be conducted in 120 adults with ADHD, aged 18–65. The intervention will be given as an add-on to standard care. Participants will be randomized to three groups. Group 1 will be given a physiotherapist-led mixed exercise programme for 12 weeks. Group 2 will receive the same intervention as group 1 with the addition of occupational therapist-led cognitive skills training. Group 3 will be the control group who will receive standard care only. The primary outcome will be reduction of ADHD symptoms measured using the World Health Organization (WHO) Adult ADHD Self-Report Scale (ASRS-v1.1), Clinical Global Impression-Severity scale (CGI-S) and CGI-Improvement scale (CGI-I). The effect will be measured within 1 week after the end of the intervention and 6 and 12 months later.

Discussion

Data collection began in March 2021. The final 12-month follow-up is anticipated to be completed by autumn 2024.

Trial registration

ClinicalTrials.gov (Identifier: NCT05049239). Registered on 20 September 2021 (last verified: May 2021).
Likelihood of identifying autistic traits with the autism spectrum quotient (AQ) in male juveniles with autism spectrum disorder (ASD) and severe behavioral problems (SBPs)
Authors: Rutten Alexa X. , Vermeiren Robert R. J. M. , Bongers Ilja L. , Van Nieuwenhuizen Chijs
Published: September 2023

Background

When screening for autism spectrum disorders (ASD), the Autism Spectrum Quotient (AQ) is generally considered to be useful. Whether the AQ is also a suitable screener for ASD in juveniles with severe behavioral problems (SBPs) is unknown. Due to the overlap of symptoms between ASD and SBPs, particularly in juveniles low on empathy, the screening capacity of the AQ might be constrained. The aim of the present study was to investigate whether (comorbid) SBPs affect the screening capacity of the AQ. The hypothesis is that male juveniles with SBPs - but without a diagnosis of ASD - will score higher than male juveniles without both SBPs and ASD.

Method

The AQ was completed by 216 male juveniles aged 15–18 years treated at an outpatient department of child and adolescent psychiatry. The 216 participants were categorized into four groups according to a clinical diagnosis of ASD and SBPs (defined as disruptive behavior disorder and/or delinquent behavior). Using multinomial logistic regression, we investigated whether the four identified groups, based on a diagnosis of ASD and SBPs, scored differently for the total score and subscales of the AQ.

Results

Participants in the group with ASD (ASD+) but without SBPs (SBP-) were more likely to report higher levels of autistic traits than the reference group without both ASD and SBPs (ASD-SBP-), except for the subscale on attention to detail (ASD+SBP- OR = 1.04; 95%CI = 0.98–1.11). Participants in the group with both ASD and SBPs were more likely to report higher levels for the total AQ score (ASD+SBP+ OR = 1.03; 95%CI = 1.00–1.05) and the communication subscale of the AQ (ASD+SBP+ OR = 1.18; 95%CI = 1.07–1.31) than the reference group without both ASD and SBPs.

Conclusion

In outpatient male juveniles, SBPs do not affect the screening capacity of the AQ for autistic traits. In spite of the well-known overlap of symptoms between ASD and SBPs, male juveniles with SBPs but without a diagnosis of ASD do not score higher on the AQ than male juveniles without SBPs and without a diagnosis of ASD.
A multisectoral and multidisciplinary endeavor: a review of diabetes self-management apps in China
Authors: Chen Meifang , Weissglass Daniel , Li Chengyi , Li Di , Wu Zixuan , Zhang Li
Published: September 2023

Background

While the use of self-management apps has considerable promise to efficiently reduce the diabetes burden that disproportionally affects low- and middle-income countries (LMICs), and the multisectoral and multidisciplinary approaches have been encouraged to be used in diabetes management, little is known about the status of the integration of these approaches in the existing diabetes self-management apps. This review examines the diabetes apps in China as an indication of the current status of integrating multisectoral and multidisciplinary approaches in diabetes mHealth care in LMICs.

Methods

Eligible diabetes apps were searched on major Chinese app stores up to December 23, 2022. The app comprehensiveness index (ranging 0–80) regarding the app functions and diabetes management domains was created. The multisectoral and multidisciplinary features were summarized using indices derived from current guidance.

Results

Sixty-six apps were reviewed, all developed by private companies. The average comprehensiveness score was 16, with many major self-management domains and functions not represented among the reviewed apps. Forty apps (61%) involved multiple sectoral entities, with public/private and private/private collaborations being the most common collaborative combinations. Thirty-seven apps (56%) involved multiple disciplines, among which endocrinology/metabolism, nutrition, and cardiovascular medicine were the top three most common disciplines. Compared to non-multidisciplinary apps, multidisciplinary apps tended to provide more comprehensive services in apps (6.14 vs. 5.18, p = 0.0345). Different sectors and disciplines tended to work independently, without robust interactions, in providing diabetes management services in the reviewed apps.

Conclusion

Multisectoral and multidisciplinary features has presented in the current diabetes self-management apps in China; however, it is still in its infancy and significant limitations existed. More engagement of civil society organizations and community groups and innovative collaborations between sectors and disciplines are needed to provide comprehensive, continuous, and patient-centered mHealth care for patients with diabetes in LMICs like China. Clear guidance for integrating and evaluating the multisectoral and multidisciplinary efforts in self-management apps is necessary to ensure the effective use of mHealth solutions for diabetes management in LMICs.
Mobility and HIV vulnerabilities among female sex workers in Guinea-Bissau: findings from an integrated bio-behavioral survey
Authors: Gorin Emma M. , Lyons Carrie E. , Jarrett Brooke A. , Djalo Mamadu A. , Barreto Kátia , Drame Fatou M. , Baral Stefan
Published: September 2023

Background

Mobility is an important risk determinant for HIV given the potential for intermittent access to HIV services. Mobility may be particularly relevant among female sex workers, (FSW) who have been shown to be at high risk for HIV in settings around the world. Data regarding the role mobility plays in exacerbating HIV risks among FSW across Sub-Saharan Africa remains limited, and data on FSW in Guinea-Bissau is sparse.

Methods

FSW in four regions of Guinea-Bissau were recruited with a respondent-driven sampling (RDS) method and participated in an integrated bio-behavioral survey between September 27, 2017 and January 26, 2018. Associations between reported general mobility, mobility to or residence in Bissau, and social and HIV vulnerabilities among FSW in Guinea-Bissau were assessed using multivariable logistic regression models. Population proportions were weighted for RDS sampling, while logistic regression models were not.

Results

Survey respondents included 323 individuals in Bissau, 45 in Bissorã, 140 in Bafatá, and 59 in Gabu. Statistical analyses demonstrated that mobility to more than one destination was significantly associated with recent sex without a condom (ie, sex without a condom within the last three sex acts) with both clients (aOR: 2.47 (95% CI: 1.08, 5.64)) and non-paying partners (aOR: 5.39 (95% CI: 2.61, 11.15)) compared to non-mobility. However, mobility to one or more locations was also associated with higher odds of receiving HIV prevention information, and mobility to more than one location was associated with participating in programming with HIV-related organizations.

Conclusions

These results suggest that while some prevention services including HIV prevention information reach mobile FSW in Guinea-Bissau more than their non-mobile counterparts, the higher rates of condomless sex among mobile FSW suggest that HIV prevention needs may remain unmet for mobile FSW in Guinea-Bissau. Additionally, the results suggest a nuanced relationship between mobility, place of residence, and HIV and social vulnerabilities and prevention indicators.
Metformin induces ferroptosis through the Nrf2/HO-1 signaling in lung cancer
Authors: Deng Chengmin , Xiong Lin , Chen Yang , Wu Kaifeng , Wu Jie
Published: September 2023

Background

Metformin is the most frequently prescribed medication for the treatment of type II diabetes mellitus and has played an anti-tumor potential in a variety of cancer types. Metformin can inhibit the growth of many cancer cells through various mechanisms, including ferroptosis. However, it is still unclear whether metformin can induce ferroptosis in lung cancer.

Methods

This study evaluated the anti-tumor effect of metformin by detecting the levels of oxidative stress factors, the levels of ferrous ions, and the expression of ferroptosis-related genes in A549 and H1299 lung cancer cell lines treated with or without metformin.

Results

The results showed that metformin treatment increased the levels of MDA, ROS and iron ions, while decreased the levels of GSH, T-SOD and CAT. Meanwhile, metformin treatment reduced the protein expression levels of Gpx4 and SLC7A11, Nrf2 and HO-1, while the addition of ferroptosis inhibitor ferrostatin-1 reversed the reduction.

Conclusions

These results demonstrated that metformin exerts anti-tumor effects by inducing ferroptosis through the Nrf2/HO-1 signaling pathway in lung cancer cells, providing a theoretical basis for drug therapy of lung cancer patients.
Serum prolactin and gonadal hormones in hemodialysis women: a meta-analysis
Authors: Zhang Kailu , Zhao Lanbo , Bin Yadi , Guo Miao , Zhou Xue , Li Min , Han Lu , Li Qiling
Published: September 2023

Background

A meta-analysis followed by PRISMA 2020 statement was performed aiming to present a whole prolactin and sex hormone profile in hemodialysis women.

Methods

Literatures were searched in PubMed, Cochrane library, Embase, and Web of science before March 11, 2023. Trial sequential analysis (TSA) was performed to test the conclusiveness of this meta-analysis. Egger’s test and trim-and-fill analysis was used to test publication bias. We took standardized mean difference (SMD) as pool effect of hormones values including prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and progesterone (P). This study was registered in PROSPERO and the number was CRD42023394503.

Results

Twenty-two articles from 13 countries were analyzed. Combining the results of TSA and meta-analysis, we found that compared with healthy control, hemodialysis women had higher PRL, follicular FSH and LH values and lower P levels (PRL: I2 = 87%, SMD 1.24, 95% CI: 0.79–1.69, p < 0.00001; FSH: I2 = 0%, SMD 0.34, 95% CI: 0.13–0.55, p = 0.002; LH: I2 = 39%, SMD 0.64, 95% CI: 0.34–0.93, p < 0.00001; P: I2 = 30%, SMD − 1.62, 95% CI: -2.04 to -1.20, p < 0.00001). What’s more, compared with women after renal transplantation, hemodialysis women had higher PRL levels (I2 = 0%, SMD 0.51, 95% CI: 0.25–0.78, p = 0.0001). There was not enough evidence to draw a conclusion on the comparison of hormones between regular and irregular menses hemodialysis women. Egger’s test and trim-and-fill analysis didn’t show significant publication bias.

Conclusions

Hemodialysis women had higher serum PRL, follicular phase FSH, LH and lower serum P values compared with healthy control. PRL values of hemodialysis women were also higher than that of women after renal transplantation.
Cone-beam computed tomography assessment of the root canal morphology of primary molars
Authors: Rahmati Afsaneh , Khoshbin Elham , Shokri Abbas , Yalfani Hadis
Published: September 2023

Background

This study aimed to assess the root canal morphology of primary molars using cone-beam computed tomography (CBCT).

Methods

This cross-sectional study evaluated 60 maxillary and mandibular primary first and second molars on CBCT scans of patients retrieved from the archives of Hamadan School of Dentistry between 2018–2020. The teeth were evaluated regarding the number of roots and canals, canal type according to the Vertucci’s classification, and root surface concavities. Data were analyzed descriptively and by independent t-test.

Results

The most frequent number of canals and roots in the maxillary right and left first molars was 3 canals (60%) and 3 roots (80%). These values were 4 canals (80%) and 5 canals (50%) with 3 roots in the maxillary right and left second molars, respectively, 4 canals (100%) and 2 roots (50%), and 3 canals (60%) and 2 roots (50%) in mandibular right and left first molars, respectively, and 4 canals (92.3%) and 3 roots (61.5%) in mandibular right and left second molars. Vertucci’s type IV was the most common canal type in mesial and distal canals, type I was the most common in mesiobuccal, mesiolingual, distobuccal, and distolingual, and types I and II were the most common in the palatal canal. The maximum and minimum concavities were noted in the buccal (26.7%) and mesial (8.3%) surfaces, respectively.

Conclusions

A wide variation exists in the number of roots and canals of maxillary and mandibular primary molars, which calls for further attention in treatment of such teeth.
Meta-analysis reveals the vaginal microbiome is a better predictor of earlier than later preterm birth
Authors: Huang Caizhi , Gin Craig , Fettweis Jennifer , Foxman Betsy , Gelaye Bizu , MacIntyre David A. , Subramaniam Akila , Fraser William , Tabatabaei Negar , Callahan Benjamin
Published: September 2023

Background

High-throughput sequencing measurements of the vaginal microbiome have yielded intriguing potential relationships between the vaginal microbiome and preterm birth (PTB; live birth prior to 37 weeks of gestation). However, results across studies have been inconsistent.

Results

Here, we perform an integrated analysis of previously published datasets from 12 cohorts of pregnant women whose vaginal microbiomes were measured by 16S rRNA gene sequencing. Of 2039 women included in our analysis, 586 went on to deliver prematurely. Substantial variation between these datasets existed in their definition of preterm birth, characteristics of the study populations, and sequencing methodology. Nevertheless, a small group of taxa comprised a vast majority of the measured microbiome in all cohorts. We trained machine learning (ML) models to predict PTB from the composition of the vaginal microbiome, finding low to modest predictive accuracy (0.28–0.79). Predictive accuracy was typically lower when ML models trained in one dataset predicted PTB in another dataset. Earlier preterm birth (< 32 weeks, < 34 weeks) was more predictable from the vaginal microbiome than late preterm birth (34–37 weeks), both within and across datasets. Integrated differential abundance analysis revealed a highly significant negative association between L. crispatus and PTB that was consistent across almost all studies. The presence of the majority (18 out of 25) of genera was associated with a higher risk of PTB, with L. iners, Prevotella, and Gardnerella showing particularly consistent and significant associations. Some example discrepancies between studies could be attributed to specific methodological differences but not most study-to-study variations in the relationship between the vaginal microbiome and preterm birth.

Conclusions

We believe future studies of the vaginal microbiome and PTB will benefit from a focus on earlier preterm births and improved reporting of specific patient metadata shown to influence the vaginal microbiome and/or birth outcomes.
Diagnostic and societal impact of implementing the syncope guidelines of the European Society of Cardiology (SYNERGY study)
Authors: Ghariq M. , van den Hout W. B. , Dekkers O. M. , Bootsma M. , de Groot B. , Groothuis J. G. J. , Harms M. P. M. , Hemels M. E. W. , Kaal E. C. A. , Koomen E. M. , de Lange F. J. , Peeters S. Y. G. , van Rossum I. A. , Rutten J. H. W. , van Zwet E. W. , van Dijk J. G. , Thijs R. D. ,   on behalf of the SYNERGY Consortium, Tuinema R. M. , Voet W. , Boerman D. B. , Firouzi M. , Fokke C.
Published: September 2023

Background

Syncope management is fraught with unnecessary tests and frequent failure to establish a diagnosis. We evaluated the potential of implementing the 2018 European Society of Cardiology (ESC) Syncope Guidelines regarding diagnostic yield, accuracy and costs.

Methods

A multicentre pre-post study in five Dutch hospitals comparing two groups of syncope patients visiting the emergency department: one before intervention (usual care; from March 2017 to February 2019) and one afterwards (from October 2017 to September 2019). The intervention consisted of the simultaneous implementation of the ESC Syncope Guidelines with quick referral routes to a syncope unit when indicated. The primary objective was to compare diagnostic accuracy using logistic regression analysis accounting for the study site. Secondary outcome measures included diagnostic yield, syncope-related healthcare and societal costs. One-year follow-up data were used to define a gold standard reference diagnosis by applying ESC criteria or, if not possible, evaluation by an expert committee. We determined the accuracy by comparing the treating physician’s diagnosis with the reference diagnosis.

Results

We included 521 patients (usual care, n = 275; syncope guidelines intervention, n = 246). The syncope guidelines intervention resulted in a higher diagnostic accuracy in the syncope guidelines group than in the usual care group (86% vs.69%; risk ratio 1.15; 95% CI 1.07 to 1.23) and a higher diagnostic yield (89% vs. 76%, 95% CI of the difference 6 to 19%). Syncope-related healthcare costs did not differ between the groups, yet the syncope guideline implementation resulted in lower total syncope-related societal costs compared to usual care (saving €908 per patient; 95% CI €34 to €1782).

Conclusions

ESC Syncope Guidelines implementation in the emergency department with quick referral routes to a syncope unit improved diagnostic yield and accuracy and lowered societal costs.

Trial registration

Netherlands Trial Register, NTR6268
ACVRL1 drives resistance to multitarget tyrosine kinase inhibitors in colorectal cancer by promoting USP15-mediated GPX2 stabilization
Authors: Lu Xiaolin , Liu Ruiqi , Liao Yuanyu , Cui Luying , Sun Haoxiu , Zhang Dongzhi , Wang Bojun , Fang Lin , Guan Xin , Yao Yuanfei , Liu Chao , Zhang Yanqiao
Published: September 2023

Background

Multitarget tyrosine kinase inhibitors (mTKIs) such as Regorafenib and Sorafenib have already been approved for the treatment of many solid tumours. However, the efficacy of mTKIs in colorectal cancer (CRC) is limited; the underlined mechanism remains largely elusive. Our study was aimed to find out the resistance mechanism of mTKIs in CRC.

Methods

RNA sequencing was used to identify the expression of Activin A receptor-like type 1 (ACVRL1) under the treatment of mTKIs. Gain/loss-of-function experiments were performed to assess the biological function of ACVRL1 in resistance to mTKIs. The underlying mechanisms of ACVRL1-mediated mTKI resistance were investigated by using liquid chromatography-mass spectrometry assays (LC-MS), co-immunoprecipitation assays (Co-IP), chromatin immunoprecipitation assays, ubiquitination assays, dual luciferase reporter assays, etc.

Results

RNA sequencing identified the activation of ACVRL1 under the treatment of mTKIs in CRC cells. ACVRL1 knockdown and overexpression significantly affects the sensitivity of CRC cells to mTKIs both in vitro and vivo. Mechanistically, we found the β-catenin/TCF-1-KCNQ1OT1/miR-7-5p axis mediated the activation of ACVRL1.

Furthermore, LC-MS assays indicated the interaction between ACVRL1 and glutathione peroxidase 2(GPX2) protein. IP assay defined ACVRL1 truncation (282–503aa) could be responsible for interacting with GPX2, and rescue experiments with ACVRL1 truncations confirmed the importance of this interaction in driving mTKI resistance. Co-IP assays confirmed that ACVRL1 associates with ubiquitin-specific peptidase 15(USP15) which directly deubiquinates GPX2 at the K187(K, lysine) site, leading to the accumulation of GPX2 protein. Rescue experiments performed with the lysine mutants in GPX2 CRISPR knockout cell model confirmed the importance of GPX2 K187 mutant. As a result, the increased ROS clearance and decreased cell apoptosis eventually lead to mTKI resistance in CRC.

Conclusions

Our results demonstrate that the Wnt/β-catenin/KCNQ1OT1/miR-7-5p/ACVRL1/GPX2 biological axis plays a vital role in CRC, targeting which may be an effective approach for overcoming mTKI resistance.
Benefit of prompt initiation of single-inhaler fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI) in patients with COPD in England following an exacerbation: a retrospective cohort study
Authors: Ismaila Afisi S. , Rothnie Kieran J. , Wood Robert P. , Banks Victoria L. , Camidge Lucinda J. , Czira Alexandrosz , Compton Chris , Sharma Raj , Millard Shannon N. , Massey Olivia , Halpin David M. G.
Published: September 2023

Background

Triple therapy is recommended for patients with chronic obstructive pulmonary disease (COPD) who remain symptomatic despite dual therapy. The optimal timing of triple therapy following an exacerbation of COPD is unknown. The outcomes of prompt (≤ 30 days) vs. delayed (31–180 days) initiation of single-inhaler triple therapy with fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI) following an exacerbation of COPD were examined.

Methods

This was a retrospective cohort study of linked English primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data. Patients aged ≥ 35 years with COPD were indexed on the first and/or earliest date of exacerbation between November 15, 2017 and March 31, 2019 with subsequent FF/UMEC/VI initiation within 180 days. Patients were required to be continuously registered with a general practitioner for ≥ 12 months prior to and following index. Subsequent exacerbations, direct medical costs, and hospital readmissions were compared between prompt and delayed initiators. Inverse probability of treatment weighting was used to adjust for measured confounders between cohorts.

Results

Overall, 1599 patients were included (prompt: 393, delayed: 1206). After weighting, prompt initiators had numerically lower moderate/severe exacerbations compared with delayed initiators (rate ratio: 0.87, 95% confidence interval [CI]: 0.76–1.01, p = 0.0587). Both all-cause and COPD-related 30-day hospital readmissions were significantly lower among patients with prompt initiation compared with delayed initiators (all-cause: 23.6% vs. 34.6%, odds ratio [95% CI]: 0.58 [0.36–0.95], p = 0.0293; COPD-related: 20.3% vs. 30.6%, odds ratio [95% CI]: 0.58 [0.35–0.96], p = 0.0347). Prompt initiators also had numerically lower all-cause total costs and significantly lower COPD-related costs per-person-per year compared with delayed initiators (COPD-related: £742 vs. £801, p = 0.0016).

Conclusion

Prompt initiation of FF/UMEC/VI following a moderate/severe exacerbation was associated with fewer subsequent exacerbations, fewer hospital readmissions, and lower COPD-related medical costs compared with delayed initiation.
Measuring efficiency of public hospitals under the impact of Covid-19: the case of Türkiye
Authors: Sülkü Seher Nur , Mortaş Alper , Küçük Aziz
Published: September 2023

The Covid-19 pandemic has had serious medical, administrative and financial effects on the health system and hospitals around the world. In Türkiye, compared to 2019 realizations, in 2020 and 2021 respectively there were 39% and 21% decrease in the number of outpatient services and 29% and 17% decline in total inpatient services of public hospitals. The main subject of this research is how the pandemic period affects the Turkish public hospitals’ efficiency. We have measured the technical efficiency of outpatient and inpatient care services of Turkish public hospitals using Stochastic Frontier Analysis (SFA). The dataset includes 563 hospitals for the years 2015 through 2021. Inputs of number of physicians, nurses and other medical staff, and number of beds and their interactions with each other are introduced to the SFA models of outputs of outpatient visits and inpatient discharges adjusted with case mix index are derived. Firstly, we found that the years associated with Covid-19 have a significant negative impact on the inpatient service efficiency. Training and Research and City Hospitals have low efficiency scores in outpatient services but high efficiency scores in inpatient services. In addition, the regions with high population rates have positive impact in outpatient efficiency and negative impact in inpatient efficiency. During the pandemic, city hospitals, have received large investments, gained a key role by increasing both the patient load and their efficiency. Future reforms can be guided by taking advantage of the efficiency differences of hospitals in different environmental factors.
Advances in biological functions and applications of apoptotic vesicles
Authors: Zou Xianghui , Lei Qian , Luo Xinghong , Yin Jingyao , chen Shuoling , Hao Chunbo , Shiyu Liu , Ma Dandan
Published: September 2023

Background

Apoptotic vesicles are extracellular vesicles generated by apoptotic cells that were previously regarded as containing waste or harmful substances but are now thought to play an important role in signal transduction and homeostasis regulation.

Methods

In the present review, we reviewed many articles published over the past decades on the subtypes and formation of apoptotic vesicles and the existing applications of these vesicles.

Results

Apoptotic bodies were once regarded as vesicles released by apoptotic cells, however, apoptotic vesicles are now regarded to include apoptotic bodies, apoptotic microvesicles and apoptotic exosomes, which exhibit variation in terms of biogenesis, sizes and properties. Applications of apoptotic vesicles were first reported long ago, but such reports have been rarer than those of other extracellular vesicles. At present, apoptotic vesicles have been utilized mainly in four aspects, including in direct therapeutic applications, in their engineering as carriers, in their construction as vaccines and in their utilization in diagnosis.

Conclusion

Building on a deeper understanding of their composition and characteristics, some studies have utilized apoptotic vesicles to treat diseases in more novel ways. However, their limitations for clinical translation, such as heterogeneity, have also emerged. In general, apoptotic vesicles have great application potential, but there are still many barriers to overcome in their investigation.