bluuebunny/crossref_metadata_2025 huggingface dataset:
Frailty is related to serum inflammageing markers: results from the VITAL study
Authors: van Sleen Yannick , Shetty Sudarshan A. , van der Heiden Marieke , Venema Milou C. A. , Gutiérrez-Melo Nicolas , Toonen Erik J. M. , van Beek Josine , Buisman Anne-Marie , van Baarle Debbie , Sauce Delphine
Published: November 2023

Frailty describes an age-associated state in individuals with an increased vulnerability and less resilience against adverse outcomes. To score frailty, studies have employed the questionnaires, such as the SF-36 and EQ-5D-3L, or the Frailty Index, a composite score based on deficit accumulation. Furthermore, ageing of the immune system is often accompanied by a state of low-grade inflammation (inflammageing). Here, we aimed to associate 29 circulating markers of inflammageing with frailty measures in a prospective cohort study to understand the mechanisms underlying ageing.

Frailty measures and inflammageing markers were assessed in 317 participants aged 25–90. We determined four different measures of frailty: the Frailty Index based on 31 deficits, the EQ-5D-3L and two physical domains of the SF-36. Serum/plasma levels of inflammageing markers and CMV/EBV seropositivity were measured using different techniques: Quanterix, Luminex or ELISA.

All four measures of frailty strongly correlated with age and BMI. Nineteen biomarkers correlated with age, some in a linear fashion (IL-6, YKL-40), some only in the oldest age brackets (CRP), and some increased at younger ages and then plateaued (CCL2, sIL-6R). After correcting for age, biomarkers, such as IL-6, CRP, IL-1RA, YKL-40 and elastase, were associated with frailty. When corrected for BMI, the number of associations reduced further.

In conclusion, inflammageing markers, particularly markers reflecting innate immune activation, are related to frailty. These findings indicate that health decline and the accumulation of deficits with age is accompanied with a low-grade inflammation which can be detected by specific inflammatory markers.
Predictors of HIV status disclosure among people living with HIV (PLHIV) in Ghana: the disclosure conundrum and its policy implications in resource limited settings
Authors: Alhassan Robert Kaba , Nutor Jerry John , Gyamerah Akua , Boakye-Yiadom Emily , Kasu Emmanuel , Acquah Evelyn , Doe Emmanuel
Published: November 2023

Background

Globally, over 40 million lives have been claimed by HIV/AIDS. In Ghana, more than 350,000 people are living with HIV. Non-disclosure of HIV status is a major barrier to HIV/AIDS eradication; yet, little is known of the determinants of HIV status disclosure in resource limited settings in Africa like Ghana.

Objective

Determine the predictors of HIV status disclosure among people living with HIV (PLHIV) and stimulate policy discourse on support systems for self-disclosure in Africa.

Methods

This is a descriptive cross-sectional study among PLHIV (n = 181) in sub-Saharan Africa, specifically the Volta region of Ghana. Bivariate probit regression was run to determine factors associated with HIV status disclosure among PLHIV.

Results

HIV status self-disclosure was reported by 50% of the respondents; nearly 65% disclosed their status to non-family members and non-partners. Significant correlates of HIV status disclosure either to partners or non-partners were marital status, monthly income, type of occupation, and being divorced due to HIV status (p < 0.05).

Conclusions

HIV status disclosure remains low in Ghana like many African countries. There is the need for a renewed policy debate on tailored guidelines for HIV status self-disclosure and targeted support systems for PLHIV to ameliorate their predicaments and promote eradication of the epidemic in Africa.
Clinical, molecular, and histological characteristics of severely necrotic and fatal mpox in HIV-infected patients
Authors: Rajme-López Sandra , Corral-Herrera Ever A. , Tello-Mercado Andrea C. , Tepo-Ponce Karen M. , Pérez-Meléndez Raúl E. , Rosales-Sotomayor Ángela , Figueroa-Ramos Grecia , López-López Karla , Domínguez-Cherit Judith G. , San-Martín-Morante Oswaldo , Saeb-Lima Marcela , Gamboa-Domínguez Armando , Ponce-de-León Alfredo , Crabtree-Ramírez Brenda , Ramos-Cervantes Pilar , Ruíz-Palacios Guillermo M.
Published: November 2023

Background

This case series of 5 patients with severely necrotic mpox highlights the predominantly necrotic nature of lesions seen in cases of severe mpox as shown by skin and lung biopsy, as well as the extensive dissemination of the infection, as shown by polymerase chain reaction (PCR) assessment in different body sites.

Case presentations

Patients were male, the median age was 37, all lived with HIV (2 previously undiagnosed), the median CD4+ cell count was 106 cells/mm3, and 2/5 were not receiving antiretroviral treatment. The most common complication was soft tissue infection. Skin and lung biopsies showed extensive areas of necrosis. Mpox PCR was positive in various sites, including skin, urine, serum, and cerebrospinal fluid. The initiation of antiretroviral treatment, worsened the disease, like that seen in immune reconstitution syndrome. Three patients died due to multiple organ failure, presumably associated with mpox since coinfections and opportunistic pathogens were ruled out.

Conclusions

Severely necrotic manifestations of mpox in people living with advanced and untreated HIV are related to adverse outcomes.
COVID-19 and migrants: lessons for pandemic preparedness from the Malaysian experience
Authors: Verghis Sharuna
Published: November 2023

Background

Aligning with global evidence related to migrants and COVID-19, the pandemic highlighted and exposed long-standing structural inequities in the context of migrant populations in Malaysia who experienced a disproportionate level of exposure to SARS-CoV-2 and COVID-19 morbidity, as well as exacerbated precarity during COVID-19 owing to disruptions to their livelihoods, health, and life.

Main body

Focusing on COVID-19 and migrant workers in Malaysia, this review addresses two research queries: (i) what are the policy responses of the government toward migrants with regard to COVID-19? (ii) what are the lessons learned from the Malaysian experience of COVID-19 and migrants that can inform pandemic preparedness, especially regarding migrant health policy?

The review used Arksey and O’Malley’s methodological framework refined by Levac, Colquhoun, and O’Brien. In addition to the PubMed, Web of Science, Scopus, and EBSCO databases, and Malaysian English language newspapers, including the Malay Mail, Malaysiakini, and the New Straits Times, the search also included reports from the websites of government ministries and departments, such as the Immigration Department, Ministry of Human Resources, Ministry of Health, and the International Trade and Industry Ministry.

Conclusion

Using the case example of Malaysia and the policy approach toward migrant populations in Malaysia during the height of the COVID pandemic in 2020 and 2021, this paper unravels complex pathways and inter-linkages between the contexts of migration and health which coalesced to engender and exacerbate vulnerability to disease and ill-health for the migrant workers. The lack of coordination and coherence in policies addressing migrant workers during the pandemic, the normalization of cheap and disposable labor in neoliberal economic regimes, and the securitization of migration were key factors contributing to the failure of migration policies to provide protection to migrant workers during COVID-19. The review suggests that policy approaches embodying the principles of Health in All Policies, a whole-of-society approach, and the promotion of safe, just, and regular migration, predicated on equity and inclusion, are integral to a comprehensive and effective response to pandemics such as COVID-19.
A highlightedly improved method for isolating and characterizing calcium oxalate crystals from tubercles of Mammillaria schumannii
Authors: Li Changying , Chen Chunli , Qin Lihong , Zheng Dengyue , Du Qian , Hou Qiandong , Wen Xiaopeng
Published: November 2023

Background

Calcium oxalate (CaOx) is the most prevalent and widespread biomineral in plants and is involved in protective and/or defensive functions against abiotic stress factors. It is, however, expected that this function has an extremely significant contribution to growth processes in plants bearing large amounts of CaOx, such as cacti growing in desert environment.

Results

In our research, small-sized CaOx crystals (≤ 20 µm) with tetrahedral or spherical shapes were observed to dominate in each epidermal and cortical cell from the tubercles of Mammillaria schumannii, a species from the Cereoideae subfamily, having tubercles (main photosynthetic organs) united with adjacent ones almost into ridges on its stem. Because they have potential significant functions, differential centrifugations after mechanical blending were used to obtain these small-sized CaOx crystals, which extremely tend to adhere to tissue or suspend in solution. And then the combined Scanning Electron Microscope Energy Dispersive System (SEM–EDS) and Raman spectroscopy were further performed to demonstrate that the extracted crystals were mainly CaC2O4·2H2O. Interestingly, spherical druses had 2 obvious abnormal Raman spectroscopy peaks of -CH and -OH at 2947 and 3290 cm−1, respectively, which may be attributed to the occluded organic matrix. The organic matrix was further extracted from spherical crystals, which could be polysaccharide, flavone, or lipid compounds on the basis of Raman spectroscopy bands at 2650, 2720, 2770, and 2958 cm−1.

Conclusions

Here we used a highlightedly improved method to effectively isolate small-sized CaOx crystals dominating in the epidermal and cortical cells from tubercles of Mammillaria schumannii, which extremely tended to adhere plant tissues or suspend in isolation solution. And then we further clarified the organic matrix getting involved in the formation of CaOx crystals. This improved method for isolating and characterizing biomineral crystals can be helpful to understand how CaOx crystals in cacti function against harsh environments such as strong light, high and cold temperature, and aridity.
Learning curve analysis of robotic-assisted total knee arthroplasty with a Chinese surgical system
Authors: Zhang Haoran , Bai Xizhuang , Wang Huisheng , Zhu Zhiyong , Li Xi
Published: November 2023

Purpose

The aim of this study was to analyze the learning curve of total operative time, bone cutting accuracy, and limb alignment in total knee arthroplasty (TKA) using a Chinese image-based knee surgery robot known as HURWA. Additionally, a comparison was conducted with conventional TKA to ascertain the benefits of robotic-assisted TKA.

Methods

In this retrospective study, we analyzed a series of patients (n = 90) who underwent robotic-assisted total knee arthroplasty using the HURWA robot between December 2021 and October 2022. The procedures were performed by one of three orthopedic surgeons with varying levels of experience. As a control group, we selected the last 30 conventional TKA cases performed by each of these three surgeons. To determine the learning curve, we recorded the operative time, bone cutting error, and pre- and post-surgery radiographs.

Results

The study found no significant differences in total operative time, bone cutting accuracy, or limb alignment among the three surgeons. Of the three surgeons, surgeon 1, who had the most experience in joint arthroplasty, reached the learning curve in case 8, with the shortest bone cutting time and robot time. Surgeon 2 reached the learning curve in case 16, while surgeon 3 reached the learning curve in case 9. There was no observable learning curve effect for bone cutting accuracy and limb alignment. However, the percentage of cases where limb alignment differed from preoperative planning by 3° or less was higher in robotic-assisted TKA (77.97%) than in conventional TKA (47.19%).

Conclusion

The study determined that the learning curve for robotic-assisted TKA using the HURWA knee surgery robot ranged from 8 to 20 cases. No observable learning curve effect was detected for bone cutting accuracy or limb alignment. Experienced surgeons using the HURWA robot for bone cutting took less time and reached the learning curve earlier. The HURWA robot achieved better limb alignment without depending on the experience of conventional TKA.
Novel research and future prospects of artificial intelligence in cancer diagnosis and treatment
Authors: Zhang Chaoyi , Xu Jin , Tang Rong , Yang Jianhui , Wang Wei , Yu Xianjun , Shi Si
Published: November 2023

Research into the potential benefits of artificial intelligence for comprehending the intricate biology of cancer has grown as a result of the widespread use of deep learning and machine learning in the healthcare sector and the availability of highly specialized cancer datasets. Here, we review new artificial intelligence approaches and how they are being used in oncology. We describe how artificial intelligence might be used in the detection, prognosis, and administration of cancer treatments and introduce the use of the latest large language models such as ChatGPT in oncology clinics. We highlight artificial intelligence applications for omics data types, and we offer perspectives on how the various data types might be combined to create decision-support tools. We also evaluate the present constraints and challenges to applying artificial intelligence in precision oncology. Finally, we discuss how current challenges may be surmounted to make artificial intelligence useful in clinical settings in the future.
Progression of duodenal neoplasia to advanced adenoma in patients with familial adenomatous polyposis
Authors: Nakahira Hiroko , Takeuchi Yoji , Shimamoto Yusaku , Ishiguro Shingo , Yunokizaki Hiroshi , Ezoe Yasumasa , Fujisawa Fumie , Ishihara Ryu , Takayama Tetsuji , Yoshida Teruhiko , Mutoh Michihiro , Ishikawa Hideki
Published: November 2023

Background

Patients with familial adenomatous polyposis (FAP) have a lifetime risk of developing duodenal adenomas approaching 100%, and the relative risk for duodenal cancer compared with the general population is high. We conducted a retrospective study to investigate the progression of non-ampullary duodenal adenomas (NADAs) and risk factors for advanced lesions in patients with FAP.

Methods

Of 248 patients with 139 pedigrees at 2 institutes, we assessed 151 patients with 100 pedigrees with a pathogenic germline variant in the adenomatous polyposis coli gene, excluding mosaic variants. We evaluated the prevalence of NADAs in patients with FAP, the progression of these adenomas to advanced adenoma during the observation period, and the risk factors for the lifetime development of high-grade dysplasia (HGD), large (≥ 10 mm) duodenal adenomas, and Spiegelman stage IV.

Results

During the median observation period of 7 years, the incidences of patients with NADAs, with more than 20 polyps, with polyps ≥ 10 mm, with HGD, and with stage IV at the last esophagogastroduodenoscopy were increased 1.6-fold, 1.7-fold, 5-fold, 22-fold, and 9-fold, respectively. Intramucosal cancer occurred in three patients (2%), but no patients developed invasive cancer during the observation period because we performed endoscopic intervention for advanced adenomas. Stage progression was observed in 71% of 113 patients. Stage IV was more common in women, patients with a history of colectomy, and those with a 3’ side mutation in their adenomatous polyposis coli gene.

Conclusions

NADAs in patients with FAP frequently become exacerbated. Our findings suggest that patients with FAP who develop duodenal adenomas should be surveyed to prevent the development of duodenal cancer.
Evaluation of the sensory environment in a large tertiary ICU
Authors: Tronstad Oystein , Flaws Dylan , Patterson Sue , Holdsworth Robert , Garcia-Hansen Veronica , Rodriguez Leonard Francisca , Ong Ruth , Yerkovich Stephanie , Fraser John F.
Published: November 2023

Background

ICU survival is improving. However, many patients leave ICU with ongoing cognitive, physical, and/or psychological impairments and reduced quality of life. Many of the reasons for these ongoing problems are unmodifiable; however, some are linked with the ICU environment. Suboptimal lighting and excessive noise contribute to a loss of circadian rhythms and sleep disruptions, leading to increased mortality and morbidity. Despite long-standing awareness of these problems, meaningful ICU redesign is yet to be realised, and the ‘ideal’ ICU design is likely to be unique to local context and patient cohorts. To inform the co-design of an improved ICU environment, this study completed a detailed evaluation of the ICU environment, focussing on acoustics, sound, and light.

Methods

This was an observational study of the lighting and acoustic environment using sensors and formal evaluations. Selected bedspaces, chosen to represent different types of bedspaces in the ICU, were monitored during prolonged study periods. Data were analysed descriptively using Microsoft Excel.

Results

Two of the three monitored bedspaces showed a limited difference in lighting levels across the day, with average daytime light intensity not exceeding 300 Lux. In bedspaces with a window, the spectral power distribution (but not intensity) of the light was similar to natural light when all ceiling lights were off. However, when the ceiling lights were on, the spectral power distribution was similar between bedspaces with and without windows. Average sound levels in the study bedspaces were 63.75, 56.80, and 59.71 dBA, with the single room being noisier than the two open-plan bedspaces. There were multiple occasions of peak sound levels > 80 dBA recorded, with the maximum sound level recorded being > 105 dBA. We recorded one new monitor or ventilator alarm commencing every 69 s in each bedspace, with only 5% of alarms actioned. Acoustic testing showed poor sound absorption and blocking.

Conclusions

This study corroborates other studies confirming that the lighting and acoustic environments in the study ICU were suboptimal, potentially contributing to adverse patient outcomes. This manuscript discusses potential solutions to identified problems. Future studies are required to evaluate whether an optimised ICU environment positively impacts patient outcomes.
Cooperation of MLL1 and Jun in controlling H3K4me3 on enhancers in colorectal cancer
Authors: Lin Xiang , Chen Ji-Dong , Wang Chen-Yu , Cai Zhen , Zhan Rui , Yang Chen , Zhang La-Ying , Li Lian-Yun , Xiao Yong , Chen Ming-Kai , Wu Min
Published: November 2023

Background

Enhancer dysregulation is one of the important features for cancer cells. Enhancers enriched with H3K4me3 have been implicated to play important roles in cancer. However, their detailed features and regulatory mechanisms have not been well characterized.

Results

Here, we profile the landscape of H3K4me3-enriched enhancers (m3Es) in 43 pairs of colorectal cancer (CRC) samples. M3Es are widely distributed in CRC and averagely possess around 10% of total active enhancers. We identify 1322 gain variant m3Es and 367 lost variant m3Es in CRC. The target genes of the gain m3Es are enriched in immune response pathways. We experimentally prove that repression of CBX8 and RPS6KA5 m3Es inhibits target gene expression in CRC. Furthermore, we find histone methyltransferase MLL1 is responsible for depositing H3K4me3 on the identified Vm3Es. We demonstrate that the transcription factor AP1/JUN interacts with MLL1 and regulates m3E activity. Application of a small chemical inhibitor for MLL1 activity, OICR-9429, represses target gene expression of the identified Vm3Es, enhances anti-tumor immunity and inhibits CRC growth in an animal model.

Conclusions

Taken together, our study illustrates the genome-wide landscape and the regulatory mechanisms of m3Es in CRC, and reveals potential novel strategies for cancer treatment.
Quartet DNA reference materials and datasets for comprehensively evaluating germline variant calling performance
Authors: Ren Luyao , Duan Xiaoke , Dong Lianhua , Zhang Rui , Yang Jingcheng , Gao Yuechen , Peng Rongxue , Hou Wanwan , Liu Yaqing , Li Jingjing , Yu Ying , Zhang Naixin , Shang Jun , Liang Fan , Wang Depeng , Chen Hui , Sun Lele , Hao Lingtong ,   The Quartet Project Team, Scherer Andreas , Nordlund Jessica , Xiao Wenming , Xu Joshua , Tong Weida , Hu Xin , Jia Peng , Ye Kai , Li Jinming , Jin Li , Hong Huixiao , Wang Jing , Fan Shaohua , Fang Xiang , Zheng Yuanting , Shi Leming
Published: November 2023

Background

Genomic DNA reference materials are widely recognized as essential for ensuring data quality in omics research. However, relying solely on reference datasets to evaluate the accuracy of variant calling results is incomplete, as they are limited to benchmark regions. Therefore, it is important to develop DNA reference materials that enable the assessment of variant detection performance across the entire genome.

Results

We established a DNA reference material suite from four immortalized cell lines derived from a family of parents and monozygotic twins. Comprehensive reference datasets of 4.2 million small variants and 15,000 structural variants were integrated and certified for evaluating the reliability of germline variant calls inside the benchmark regions. Importantly, the genetic built-in-truth of the Quartet family design enables estimation of the precision of variant calls outside the benchmark regions. Using the Quartet reference materials along with study samples, batch effects are objectively monitored and alleviated by training a machine learning model with the Quartet reference datasets to remove potential artifact calls. Moreover, the matched RNA and protein reference materials and datasets from the Quartet project enables cross-omics validation of variant calls from multiomics data.

Conclusions

The Quartet DNA reference materials and reference datasets provide a unique resource for objectively assessing the quality of germline variant calls throughout the whole-genome regions and improving the reliability of large-scale genomic profiling.
Single-cell multiomics of the human retina reveals hierarchical transcription factor collaboration in mediating cell type-specific effects of genetic variants on gene regulation
Authors: Wang Jun , Cheng Xuesen , Liang Qingnan , Owen Leah A. , Lu Jiaxiong , Zheng Yiqiao , Wang Meng , Chen Shiming , DeAngelis Margaret M. , Li Yumei , Chen Rui
Published: November 2023

Background

Systematic characterization of how  genetic variation modulates gene regulation in a cell type-specific context is essential for understanding complex traits. To address this question, we profile gene expression and chromatin accessibility in cells from healthy retinae of 20 human donors through single-cell multiomics and genomic sequencing.

Results

We map eQTL, caQTL, allelic-specific expression, and allelic-specific chromatin accessibility in major retinal cell types. By integrating these results, we identify and characterize regulatory elements and genetic variants effective on gene regulation in individual cell types. The majority of identified sc-eQTLs and sc-caQTLs display cell type-specific effects, while the cis-elements containing genetic variants with cell type-specific effects are often accessible in multiple cell types. Furthermore, the transcription factors whose binding sites are perturbed by genetic variants tend to have higher expression levels in the cell types where the variants exert their effects, compared to the cell types where the variants have no impact. We further validate our findings with high-throughput reporter assays. Lastly, we identify the enriched cell types, candidate causal variants and genes, and cell type-specific regulatory mechanism underlying GWAS loci.

Conclusions

Overall, genetic effects on gene regulation are highly context dependent. Our results suggest that cell type-dependent genetic effect is driven by precise modulation of both trans-factor expression and chromatin accessibility of cis-elements. Our findings indicate hierarchical collaboration among transcription factors plays a crucial role in mediating cell type-specific effects of genetic variants on gene regulation.
RCC2 promotes prostate cancer cell proliferation and migration through Hh/GLI1 signaling pathway and cancer stem-like cells
Authors: Wang Shenghan , Lei Zhentao , Liu Wei , Xiong Jie , Shi Yuqiang , Yang Lin , Gao Qiang , Le Kai , Zhang Bao
Published: November 2023

Background

Regulator of chromosome condensation 2 (RCC2) was a telophase disk-binding protein on mitosis, and functions as an oncogene in many human cancers. However, its role on prostate cancer (PCa) was unknown. The goal of this study is to explore the function of RCC 2 on PCa development.

Methods

The expression of RCC2 and its methylation level, its correlation with lymph node metastasis or disease-free survival (DFS) was analyzed using TCGA database. The effect of RCC2 on PCa cell proliferation, migration and invasion were detected using CCK-8, cell colony formation, Transwell and wood healing assays. RNA-seq and GSEA analysis were used to search the downstream genes and pathways of RCC2 in mediated PCa progression. Western blot was used to detect the proteins in PCa cells transfected with indicated siRNAs or plasmids.

Results

RCC2 had high expression and low promoter methylation level in PCa, and its expression was correlated with regional node metastasis and disease-free survival. Cell proliferation, migration, invasion and EMT of PCa cells in vitro were greatly enhanced after RCC2 overexpression, while the RCC2 knockdown suppressed these processes. RNA-seq and GSEA results showed the Hedgehog signaling regulator Gli1 and Gli3 were involved in RCC2 knockdown DU145 cells. Gli1 was also a marker of cancer stem-like cells (CSCs). Mechanistically, RCC2 induced cell growth, EMT, CSCs markers through Gli1; inhibiting Gli1 expression using siGli1 or GLI inhibitor suppressed cell progression in vitro and tumor growth in vivo.

Conclusion

In summary, RCC2 promoted PCa development through Hh/Gli1 signaling pathway via regulating EMT and CSCs.
The efficacy of a blended intervention to improve physical activity and protein intake for optimal physical recovery after oncological gastrointestinal and lung cancer surgery, the Optimal Physical Recovery After Hospitalization (OPRAH) trial: study protocol for a randomized controlled multicenter trial
Authors: de Leeuwerk Marijke , de Groot Vincent , Dam Suzanne ten , Kruizenga Hinke , Weijs Peter , Geleijn Edwin , van der Leeden Marike , van der Schaaf Marike ,   on behalf of the OPRAH consortium, Dickhoff Chris , Besselink Marc G. , Tuynman Jurriaan B. , van Berge Henegouwen Mark I. , Erdmann Joris I. , Huijsmans Rosalie J. , van der Ploeg Hidde P. , Eskes Anne M. , Pijnappels Mirjam A. G. M. , van Leeuwen Liesbeth Schuijs , Smits Anke B. , van Dijk Jasmijn , Grimbergen Eva
Published: November 2023

Background

Improving physical activity, especially in combination with optimizing protein intake, after surgery has a potential positive effect on recovery of physical functioning in patients after gastrointestinal and lung cancer surgery. The aim of this randomized controlled trial is to evaluate the efficacy of a blended intervention to improve physical activity and protein intake after hospital discharge on recovery of physical functioning in these patients.

Methods

In this multicenter single-blinded randomized controlled trial, 161 adult patients scheduled for elective gastrointestinal or lung cancer surgery will be randomly assigned to the intervention or control group. The purpose of the Optimal Physical Recovery After Hospitalization (OPRAH) intervention is to encourage self-management of patients in their functional recovery, by using a smartphone application and corresponding accelerometer in combination with coaching by a physiotherapist and dietician during three months after hospital discharge. Study outcomes will be measured prior to surgery (baseline) and one, four, eight, and twelve weeks and six months after hospital discharge. The primary outcome is recovery in physical functioning six months after surgery, and the most important secondary outcome is physical activity. Other outcomes include lean body mass, muscle mass, protein intake, symptoms, physical performance, self-reported limitations in activities and participation, self-efficacy, hospital readmissions and adverse events.

Discussion

The results of this study will demonstrate whether a blended intervention to support patients increasing their level of physical activity and protein intake after hospital discharge improves recovery in physical functioning in patients after gastrointestinal and lung cancer surgery.

Trial registration

The trial has been registered at the International Clinical Trials Registry Platform at 14–10-2021 with registration number NL9793. Trial registration data are presented in Table 1.
Analgesic effect of nitrous oxide during manual therapy after anterior cruciate ligament reconstruction: a study protocol for a randomized controlled trial
Authors: Wang Ziyang , Wang Fei , Li Yuxiang , Xing Yihui , Jiang Xiaochen , Li Cui , Ding Zhiguo , Tang Lu
Published: November 2023

Background

Many patients during manual therapy after anterior ligament reconstruction will experience severe pain, which has a negative impact on their rehabilitation. However, there is rarely an analgesic method for these patients during rehabilitation. Nitrous oxide with rapid analgesic and sedative effects is often used to relieve pain in minor procedures. The purpose of this study is to determine whether or not nitrous oxide analgesia decreases pain compared to oxygen during manual therapy after anterior ligament reconstruction.

Methods/design

This single-center, randomized, double-blind and controlled trial will recruit 120 patients. Patients ≥ 18 years old undergoing manual therapy after anterior ligament reconstruction (1 month post-operative) with acute pain (VAS ≥ 4) are included. The main exclusion criteria included the following: pulmonary embolism, intestinal obstruction, pneumothorax. Patients will be randomly allocated to the intervention group (A) and the control group (B) in a ratio of 1:1. Doctors, therapists, patients, and data collectors are all blind to the study. The manual therapy will be performed by therapists. Nurses who implemented the intervention handed the doctors envelopes containing the patients’ codes and allocation of A or B. Group A will receive a pre-prepared nitrous oxide/oxygen mixture plus conventional treatment (no analgesic) given as 30-min treatment sessions, once daily, and group B will receive oxygen plus conventional treatment (no analgesic) under the same conditions. Assessments will be taken 2 min before the intervention (T0), 5 min after the beginning of the intervention (T1), and 5 min after the intervention finished (T2). The primary outcome is pain score. Secondary outcomes include vital signs, side effects, joint range of motion, adjuvant analgesia need, therapist and patient satisfaction, and whether willing to receive the same gas again.

Expected outcomes

We expect nitrous oxide inhalation to have a beneficial effect on the pain of patients who receive manual therapy after anterior ligament reconstruction.

Discussion

If this treatment appears beneficial, it could improve patients’ satisfaction and quality of life potentially and even be implemented widely in hospital and rehabilitation settings.

Trial registration

ClinicalTrials.gov identifier, ChiCTR2200061175 (Version 2.0 June 15, 2022), https://www.chictr.org.cn.
Effects of a single dose of amisulpride on functional brain changes during reward- and motivation-related processing using task-based fMRI in healthy subjects and patients with major depressive disorder — study protocol for a randomized clinical trial
Authors: Carstens Luisa , Popp Margot , Keicher Christian , Hertrampf Rita , Weigner David , Meiering Marvin S. , Luippold Gerd , Süssmuth Sigurd D. , Beckmann Christian F. , Wunder Andreas , Grimm Simone
Published: November 2023

Background

Anhedonia and other deficits in reward- and motivation-related processing in psychiatric patients, including patients with major depressive disorder (MDD), represent a high unmet medical need. Neurobiologically, these deficits in MDD patients are mainly associated with low dopamine function in a frontostriatal network. In this study, alterations in brain activation changes during reward processing and at rest in MDD patients compared with healthy subjects are explored and the effects of a single low dose of the dopamine D2 receptor antagonist amisulpride are investigated.

Methods

This is a randomized, controlled, double-blind, single-dose, single-center parallel-group clinical trial to assess the effects of a single dose of amisulpride (100 mg) on blood-oxygenation-level-dependent (BOLD) responses during reward- and motivation-related processing in healthy subjects (n = 60) and MDD patients (n = 60). Using functional magnetic resonance imaging (fMRI), BOLD responses are assessed during the monetary incentive delay (MID) task (primary outcome). Exploratory outcomes include BOLD responses and behavioral measures during the MID task, instrumental learning task, effort-based decision-making task, social incentive delay task, and probabilistic reward task as well as changes in resting state functional connectivity and cerebral blood flow.

Discussion

This study broadly covers all aspects of reward- and motivation-related processing as categorized by the National Institute of Mental Health Research Domain Criteria and is thereby an important step towards precision psychiatry. Results regarding the immediate effects of a dopaminergic drug on deficits in reward- and motivation-related processing not only have the potential to significantly broaden our understanding of underlying neurobiological processes but might eventually also pave the way for new treatment options.

Trial registration

ClinicalTrials.gov NCT05347199. April 12, 2022.
Effects of a physical activity and endometriosis-based education program delivered by videoconference on endometriosis symptoms: the CRESCENDO program (inCRease physical Exercise and Sport to Combat ENDOmetriosis) protocol study
Authors: Escriva-Boulley Géraldine , Philip Charles-André , Warembourg Sophie , Lenotre Lionel , Flore Patrice , Faure Patrice , Michy Thierry , Letouzey Vincent , Arnold Carole , Piluso Claire , Chalmel Loic , Kacem Ramzi , Blum Georges Fabrice , Detayrac Renaud , Trocmé Candice , Brigaud Isabelle , Herbach Ulysse , Branche Patricia , Faller Emilie , Chalabaev Aïna
Published: November 2023

Background

Endometriosis is a chronic disease characterized by growth of endometrial tissue outside the uterine cavity which could affect 200 million women (The term “woman” is used for convenience. Individuals gendered as man or as nonbinary can also suffer from this disease) worldwide. One of the most common symptoms of endometriosis is pelvic chronic pain associated with fatigue. This pain can cause psychological distress and interpersonal difficulties. As for several chronic diseases, adapted physical activity could help to manage the physical and psychological symptoms. The present study will investigate the effects of a videoconference-based adapted physical activity combined with endometriosis-based education program on quality of life, pain, fatigue, and other psychological symptoms and on physical activity.

Methods

This multicentric randomized-controlled trial will propose to 200 patients with endometriosis to be part of a trial which includes a 6-month program with 45 min to more than 120 min a week of adapted physical activity and/or 12 sessions of endometriosis-based education program. Effects of the program will be compared to a control group in which patients will be placed on a waiting list. All participants will be followed up 3 and 6 months after the intervention. None of the participants will be blind to the allocated trial arm. The primary outcome measure will be quality of life. Secondary outcomes will include endometriosis-related perceived pain, fatigue, physical activity, and also self-image, stereotypes, motivational variables, perceived support, kinesiophobia, basic psychological need related to physical activity, and physical activity barriers. General linear models and multilevel models will be performed. Predictor, moderator, and mediator variables will be investigated.

Discussion

This study is one of the first trials to test the effects of a combined adapted physical activity and education program for improving endometriosis symptoms and physical activity. The results will help to improve care for patients with endometriosis.

Trial registration

ClinicalTrials.gov, NCT05831735. Date of registration: April 25, 2023
Home-based rehabilitation training with human key point detection for chronic low back pain patients: a randomized controlled trial protocol
Authors: Fuming Zheng , Zhicheng Li , Huanjie Huang , Xinna Zhang , Rong Chen , Jiahui Peng , Liming Yang , Xi Chen , Chuhuai Wang
Published: November 2023

Background

Core stability exercise (CSE) is a globally acknowledged intervention for managing chronic low back pain. However, the sustained adherence of patients with chronic low back pain to CSE can be challenging, mainly due to the absence of supervision and guidance from physical therapists during home-based exercise sessions. Consequently, exercise compliance tends to decline, resulting in suboptimal long-term effectiveness of the intervention. In this trial, our primary aim is to evaluate the potential therapeutic equivalence between home-based rehabilitation training employing key point identification technology and exercise guidance administered in a hospital setting.

Methods

In this trial, we will randomly assign 104 adults with chronic low back pain (CLBP) to either an intervention or control group, with 52 participants in each group. Both interventions will consist of three weekly 0.5-h sessions of core stability exercise (CSE). The intervention group will engage in home rehabilitation training utilizing key identification technology for movement, while the control group will perform supervised exercises in a hospital setting. Outcome assessments will be conducted at 4 weeks and 16 weeks after randomization. The primary outcome measure will be the change in pain intensity based on numeric rating scale (NRS scores) from baseline to 4 weeks. Secondary outcomes will include changes in physical function (measured by the Oswestry Disability Index (ODI)) and lumbar spine mobility as well as activity participation and treatment satisfaction.

Discussion

If home-based rehabilitation method is demonstrated to be non-inferior or even superior to traditional face-to-face exercise guidance, it could significantly advance the adoption of digital medical care and contribute to improving the overall health of the population.

Trial registration

NCT05998434. Registered on 16 August 2023.
Comparison of amiodarone and esmolol for prevention of reperfusion ventricular fibrillation in individuals undergoing heart valve or aortic surgery: a study protocol for a randomized controlled clinical trial
Authors: Zhu Dan , Li Yu , Tian A-yong , Wang Hong-nan
Published: November 2023

Background

Amiodarone and esmolol can help to prevent and treat post-cardiac surgery reperfusion ventricular fibrillation. However, the relative efficacies of these two drugs remain unknown. The aim of the current trial is to compare the performances of amiodarone and esmolol for preventing reperfusion ventricular fibrillation following open heart surgery.

Methods/design

This is a single-center, prospective, double-blind, controlled clinical trial. A total of 260 patients undergoing heart valve or aortic surgery will be assigned randomly to treatment with prophylactic esmolol (intervention group) or amiodarone (control group). The main outcome is the incidence of reperfusion ventricular fibrillation following aortic opening during extracorporeal circulation. The secondary outcomes are the rate of automatic cardiac resuscitation, energy and frequency of electrical defibrillation, number of electrical defibrillations, and pacemaker use in the two groups of patients. Information on the patients’ general condition and the durations of anesthesia, extracorporeal circulation, aortic occlusion, and operation time will be recorded. We will also compare the heart rate, mean arterial pressure, and central venous pressure between the two groups of patients at induction of anesthesia (T1), start of surgery (T2), start of extracorporeal circulation (T3), aortic block (T4), aortic opening (T5), after opening for 10 (T6), 20 (T7), and 30 min (T8), at cessation of extracorporeal circulation (T9), and at the end of surgery (T10) and compare blood gas analysis results at T1, T5, T9, and T10.

Discussion

This study will determine if prophylactic esmolol is more effective than amiodarone for reducing the incidence of reperfusion ventricular fibrillation in patients undergoing heart valve or aortic surgery.

Trial registration

China Clinical Trials Registry ChiCTR1900026429. Registered on 2019.10.9.
Comparison of the initial and residual speed of Ixodes scapularis kill on dogs treated with a single dose of Bravecto® Chew (25 mg/kg fluralaner) or Simparica TRIO® (1.2 mg/kg sarolaner, 24 µg/kg moxidectin, 5 mg/kg pyrantel)
Authors: Reif Kathryn E. , Bickmeier Naemi P. , Herrin Brian H. , Dryden Michael W. , Normile Dorothy M. , Jesudoss Chelladurai Jeba R. J. , Miller Kamilyah R. , Flowers Macy R. , Kang Qing
Published: November 2023

Background

Compliant ectoparasiticide product use is a comprehensive way to control ticks and reduce the risk of tick-borne pathogen transmission to dogs. Because the systemically acting isoxazoline ectoparasiticides require tick attachment for drug delivery, fast speed of kill is essential to minimize tick-borne pathogen transmission risk.

Methods

Dogs of satisfactory tick-carrying capacity were randomly allocated to treatment groups and administered, per label instructions, Bravecto® Chews (minimum 25 mg/kg fluralaner), Simparica TRIO® (minimum 1.2 mg/kg sarolaner, 24 µg/kg moxidectin, 5 mg/kg pyrantel), or no treatment. Dogs were infested with approximately 50 unfed adult (35 female, 15 male) Ixodes scapularis on Day -2, 21 and 28. Live tick counts were performed at 4, 8, 12 and 24 h post-treatment (Day 0) and post-infestation on Day 21 and 28. Tick control efficacy was determined by comparing live tick means for each product-treated group to the untreated control group and each other at all time points using a linear mixed model. The percent of dogs free of live ticks was analyzed using the Fisher’s exact test for treatment group comparison.

Results

The untreated control group maintained adequate tick infestations throughout the study. Using geometric means, an existing I. scapularis infestation was controlled by 99.7% and 93.0% 12 h post-treatment and by 100% and 99.5% 24 h post-treatment, for Bravecto® and Simparica TRIO®-treated dogs, respectively. Ixodes scapularis infestations were controlled more quickly for Bravecto®- compared to Simparica TRIO®-treated dogs on Day 21 at 8 h (efficacy 74.0% vs. 0.0%, p = 0.003) and 12 h (efficacy 99.2% vs. 39.4%, p < 0.001) post-infestation and Day 28 at 8 h (efficacy 92.2% vs. 0.0%, p < 0.001) and 12 h (efficacy 99.6% vs. 27.7%, p < 0.001) post-infestation. On Day 28 post-treatment, the efficacy of Bravecto® and Simparica TRIO® to control a new I. scapularis infestation was 100% and 96.6%, respectively, by 24 h post-infestation. Of product-treated dogs, 100% of Bravecto®-treated dogs were free of live ticks by 24 h post-treatment or post-infestation. No treatment-related adverse reactions occurred during the study.

Conclusions

Ixodes scapularis infestations are controlled more quickly 21 and 28 days post-treatment for dogs administered a single dose of Bravecto® compared to dogs administered a single dose of Simparica TRIO®.

Graphical Abstract
Meeting report: transposable elements at the crossroads of evolution, health and disease 2023
Authors: Arkhipova Irina R. , Burns Kathleen H. , Chiappinelli Katherine B. , Chuong Edward B. , Goubert Clement , Guarné Alba , Larracuente Amanda M. , Lee E. Alice , Levin Henry L.
Published: November 2023

The conference “Transposable Elements at the Crossroads of Evolution, Health and Disease” was hosted by Keystone Symposia in Whistler, British Columbia, Canada, on September 3–6, 2023, and was organized by Kathleen Burns, Harmit Malik and Irina Arkhipova. The central theme of the meeting was the incredible diversity of ways in which transposable elements (TEs) interact with the host, from disrupting the existing genes and pathways to creating novel gene products and expression patterns, enhancing the repertoire of host functions, and ultimately driving host evolution. The meeting was organized into six plenary sessions and two afternoon workshops with a total of 50 invited and contributed talks, two poster sessions, and a career roundtable. The topics ranged from TE roles in normal and pathological processes to restricting and harnessing TE activity based on mechanistic insights gained from genetic, structural, and biochemical studies.
The impact of the Iranian health transformation plan policy on equitable access to medical imaging services in West Iran
Authors: Saran Maryam , Teli Banafsheh Darvishi , Rezapour Aziz , Motlagh Soraya Nouraei , Behzadifar Meysam , Haghighatfard Payam , Bragazzi Nicola Luigi , Behzadifar Masoud
Published: November 2023

Objective

Equity in the delivery of health services, including diagnostic imaging, is crucial to achieving universal health coverage. The Health Transformation Plan (HTP), launched in 2014, represents a major healthcare policy to improve the quality and accessibility of healthcare services. This study aimed to explore the impact of the HTP on equity in the access to medical imaging in Lorestan province, located in west Iran, from 2014 to 2023. Annual growth rates (AGR) of imaging devices were calculated, whilst equity assessment of medical imaging distribution was carried out by means of the Gini coefficient and the Lorenz curve per 100,000 population. The latter was generated using the cumulative distribution of imaging devices, as well as the cumulative population ratio.

Results

Between 2014 and 2023, the number of imaging devices has increased threefold. The AGR of installing CT and MRI scanners in Lorestan province increased between 2014 and 2023. The Gini coefficients increased from 0.12 for CT and 0.16 for MRI in 2014 to 0.33 in 2023 for both devices. This indicates a decrease in equity in access to these fundamental health technologies despite the increase in their figures. Policymakers should better allocate medical equipment based on the specific health needs of different regions throughout Iran.