bluuebunny/crossref_metadata_2025 huggingface dataset:
Experiences and self-care of pregnant nurses with gestational diabetes mellitus: a qualitative study
Authors: He Jing , Wang Hui , Chen Xiaoli
Published: January 2024

Background

Pregnant nurses are at high risk of developing gestational diabetes mellitus (GDM), and nurses diagnosed with GDM face challenges in balancing disease management and work, which affects maternal and child health and the quality of care. GDM requires significant changes to lifestyle and physical activity to control blood glucose levels, which is key to reducing adverse pregnancy outcomes. However, few studies have focused on the experiences of pregnant nurses with GDM. This study aimed to gain insight into the experiences of pregnant nurses with GDM in China in terms of their illness, work burdens, and self-care.

Methods

This qualitative study used an interpretative phenomenological analysis. Face-to-face semi-structured in-depth interviews were conducted with pregnant nurses with GDM to investigate their experiences and self-care. The study was performed at Chongqing’s maternal and child health hospital in China. A purposive sampling was used. Nine pregnant nurses diagnosed with GDM were recruited and interviewed.

Results

The interview data generated four themes and 11 sub-themes. The four themes were ‘the perceptions and feelings of GDM’, ‘experiences of lifestyle changes’, ‘social support needs’, and ‘health expectations and risk perception.’

Conclusion

Many factors such as the unique occupational environment, overwork, occupational pressure, shift work, family status, and education level may lead to difficulties in managing blood glucose in nurses with GDM. These findings suggest that managers should pay more attention to nurses with GDM and develop personalized medical care and work arrangements. These measures can improve the self-care and well-being of nurses with GDM and promote the health of nurses and their offspring.
Attachment styles and healthcare utilization: exploring the role of the patient-doctor relationship
Authors: Schmalbach I. , Franke G. H. , Häuser W. , Strauss B. , Petrowski K. , Brähler Elmar
Published: January 2024

Background

With the purpose of improving healthcare, past research has examined the link between healthcare utilization and attachment. It is suggested that an individual’s attachment style influences both the quality of their patient-physician relationship and healthcare utilization patterns. Nevertheless, most studies concentrate on the individual aspect, overlooking the dyadic dimension; specifically, the investigation of how insecure attachment relates to health behavior within patient-physician relationships. This gap leaves the role of the patient-doctor relationship in this process unclear. Therefore, to elucidate this complex interplay, we hypothesized that the correlation between attachment and healthcare utilization is mediated by the quality of the patient-physician-relationship.

Method

Participant selection was based on electoral districts, a random-route procedure, and the Kish selection grid. The participants were visited by a trained interviewer who collected psychometric and sociodemographic information. Participants answered the Experiences in Close Relationships-Revised questionnaire (ECR-RD8) and the Patient-Doctor Relationship Questionnaire (PDRQ-9). Additionally, participants were asked about their healthcare utilization. The final sample consisted of N = 2.275 participants.

Results

In average the participants reported consulting their primary health care practitioner M(SD) = 4.44 (4.76) times in the past 12 months. Generally, the participants rated the quality of the relationship with their primary health care practitioner close to “totally appropriate” (M = 4.12 ± .69). The degree of insecure attachment manifested towards the lower extremity of the scale. The total effect of the mediation analyses was significant. Regardless, the indirect effect indicated a trend result with minimal effect sizes.

Conclusion

The findings of the current study bridged the gap between attachment styles and healthcare utilization. Nonetheless, our results suggested insufficient support for the mediating role of the primary care physician in the relationship between attachment style and healthcare utilization. Considering the characteristics of the sample, this outcome may not apply in a clinical context. However, further research is needed to shed light in the revealed trends and indicate implications.
Interactions of genetic variations in FAS, GJB2 and PTPRN2 are associated with noise-induced hearing loss: a case-control study in China
Authors: Wu Shan , Wu Zhidan , Chen Manlian , Zhong Xiangbin , Gu Haoyan , Du Wenjing , Liu Weidong , Lang Li , Wang Junyi
Published: January 2024

Background

This study aimed to screen and validate noise-induced hearing loss (NIHL) associated single nucleotide polymorphisms (SNPs), construct genetic risk prediction models, and evaluate higher-order gene-gene, gene-environment interactions for NIHL in Chinese population.

Methods

First, 83 cases and 83 controls were recruited and 60 candidate SNPs were genotyped. Then SNPs with promising results were validated in another case-control study (153 cases and 252 controls). NIHL-associated SNPs were identified by logistic regression analysis, and a genetic risk model was constructed based on the genetic risk score (GRS), and classification and regression tree (CART) analysis was used to evaluate interactions among gene-gene and gene-environment.

Results

Six SNPs in five genes were significantly associated with NIHL risk (p < 0.05). A positive dose-response relationship was found between GRS values and NIHL risk. CART analysis indicated that strongest interaction was among subjects with age ≥ 45 years and cumulative noise exposure ≥ 95 [dB(A)·years], without personal protective equipment, and carried GJB2 rs3751385 (AA/AB) and FAS rs1468063 (AA/AB) (OR = 10.038, 95% CI = 2.770, 47.792), compared with the referent group. CDH23, FAS, GJB2, PTPRN2 and SIK3 may be NIHL susceptibility genes.

Conclusion

GRS values may be utilized in the evaluation of the cumulative effect of genetic risk for NIHL based on NIHL-associated SNPs. Gene-gene, gene-environment interaction patterns play an important role in the incidence of NIHL.
Navigating challenges: optimising methods for primary cell culture isolation
Authors: Piwocka Oliwia , Musielak Marika , Ampuła Karolina , Piotrowski Igor , Adamczyk Beata , Fundowicz Magdalena , Suchorska Wiktoria Maria , Malicki Julian
Published: January 2024

Primary cell lines are invaluable for exploring cancer biology and investigating novel treatments. Despite their numerous advantages, primary cultures are laborious to obtain and maintain in culture. Hence, established cell lines are still more common. This study aimed to evaluate a range of techniques for isolating primary breast cancer cultures, employing distinct enzymatic compositions, incubation durations, and mechanical approaches, including filtration. Out of several protocols, we opted for a highly effective method (Method 5) that gave rise to a primary cell culture (BC160). This method combines mechanical disaggregation and enzymatic digestion with hyaluronidase and collagenase. Moreover, the paper addresses common issues in isolating primary cultures, shedding light on the struggle against fibroblasts overgrowing cancer cell populations. To make primary cell lines a preferred model, it is essential to elaborate and categorise isolation methods, develop approaches to separate heterogeneous cultures and investigate factors influencing the establishment of primary cell lines.
Risk of low bone mineral density in patients with haemophilia: a systematic review and meta-analysis
Authors: Zhou Haojing , Chen Lei , Su Hai , Chen Guoqian , Tong Peijian
Published: January 2024

Introduction

Patients with haemophilia (PWH) may have lower bone mineral density (BMD). The risk of low BMD in PWH has not been comprehensively analysed. This study aimed to examine the risk of low BMD and changes in BMD in PWH.

Methods

A comprehensive systematic search was performed in 4 databases: PubMed, Embase, Web of Science, and Cochrane Library. The last search was carried out on 11 December 2022. Review Manager 5.4 and Stata 16 were used for meta-analysis. Odds ratios were calculated by the incidence of low BMD between the haemophilia and control groups in each study. A meta-analysis of the odds ratios for each study was performed to estimate pooled odds ratios. Fixed effects models or random effects models were used to assess outcomes. Heterogeneity was evaluated using Higgins’ I2. Subgroup analysis and sensitivity analysis were performed to interpret the potential source of heterogeneity. A funnel plot, Egger’s regression test, and the trim-and-fill method were used to assess publication bias.

Results

19 of 793 studies, published between 2004 and 2022, that were identified by search strategy were included in this meta-analysis. The risk for low BMD was approximately four times higher compared to controls. PWH have significantly lower lumbar spine, femoral neck, and total hip BMD. Subgroup analysis showed that the risk of low BMD did not increase significantly in developed countries. Very low heterogeneity was observed in the meta-analysis of the risk of low BMD. The result from Egger’s regression test suggested that there may be publication bias. However, the meta-analysis results did not alter after the trim-and-fill correction and the findings were robust.

Conclusion

Haemophilia was associated with an increased risk of low BMD. However, the risk of low BMD did not increase significantly in developed countries. And BMD was reduced in PWH, regardless of age, region, or economic ability. For PWH, our concerns should extend beyond bleeding and osteoarthritis to encompass BMD starting at a young age.
Mussel-inspired electroactive, antibacterial and antioxidative composite membranes with incorporation of gold nanoparticles and antibacterial peptides for enhancing skin wound healing
Authors: Dong Yongkang , Wang Zheng , Wang Jiapeng , Sun Xuedi , Yang Xiaoyu , Liu Guomin
Published: January 2024

Large skin wounds are one of the most important health problems in the world. Skin wound repair and tissue regeneration are complex processes involving many physiological signals, and effective wound healing remains an enormous clinical challenge. Therefore, there is an urgent need for a strategy to rapidly kill bacteria, promote cell proliferation and accelerate wound healing. At present, electrical stimulation (ES) is often used in the clinical treatment of skin wounds and can simulate the endogenous biological current of the body and accelerate the repair process of skin wounds. However, a single ES strategy has difficulty covering the entire wound area, which may lead to unsatisfactory therapeutic effects. To overcome this deficiency, it is essential to develop a collaborative treatment strategy that combines ES with other treatments. In this study, gold nanoparticles and antibacterial peptides (Os) were loaded on the surface of poly(lactic-co-glycolic acid) (PLGA) material through the reducibility and adhesion of polydopamine (PDA) and improved the electrical activity, anti-inflammatory, antibacterial and biocompatibility properties of the polymer material. At the same time, this composite membrane material (Os/Au-PDA@PLGA) combined with ES was used in wound therapy to improve the wound healing rate. The results show that the new wound repair material has good biocompatibility and can effectively promote cell proliferation and migration. Through the combined application of gold nanoparticles and antibacterial peptides Os, the polymer materials have more efficient bactericidal and antioxidant effects. The antibacterial experiment results showed that gold nanoparticles could further enhance the antibacterial activity of antibacterial peptides. Furthermore, the Os/Au-PDA@PLGA composite membrane has good hydrophilicity and electrical activity, which can provide a more favorable cell microenvironment for wound healing. In vivo studies using a full-thickness skin defect model in rats showed that the Os/Au-PDA@PLGA composite membrane had a better therapeutic effect than the pure PLGA material. More importantly, the combination of the Os/Au-PDA@PLGA composite with ES significantly accelerated the rate of vascularization and collagen deposition and promoted wound healing compared with non-ES controls. Therefore, the combination of the Au/Os-PDA@PLGA composite membrane with ES may provide a new strategy for the effective treatment of skin wounds.
TrkA promotes MDM2-mediated AGPS ubiquitination and degradation to trigger prostate cancer progression
Authors: Zhang Yu , Huang Zhenlin , Li Keqiang , Xie Guoqing , Feng Yuankang , Wang Zihao , Li Ningyang , Liu Ruoyang , Ding Yinghui , Wang Jun , Yang Jinjian , Jia Zhankui
Published: January 2024

Background

As a novel necrosis manner, ferroptosis has been increasingly reported to play a role in tumor progression and treatment, however, the specific mechanisms underlying its development in prostate cancer remain unclear. Growing evidence showed that peroxisome plays a key role in ferroptosis. Herein, we identified a novel mechanism for the involvement of ferroptosis in prostate cancer progression, which may provide a new strategy for clinical treatment of prostate cancer.

Methods

Label-Free Mass spectrometry was used to screen and identify candidate proteins after ferroptosis inducer-ML210 treatment. Immunohistochemistry was undertaken to explore the protein expression of AGPS in prostate cancer tissues compared with normal tissues. Co-immunoprecipitation and GST pull-down were used to identify the directly binding of AGPS to MDM2 in vivo and in vitro. CCK8 assay and colony formation assay were used to illustrate the key role of AGPS in the progression of prostate cancer in vitro. The xenograft model was established to verify the key role of AGPS in the progression of prostate cancer in vivo.

Results

AGPS protein expression was downregulated in prostate cancer tissues compared with normal tissues from the first affiliated hospital of Zhengzhou University dataset. Lower expression was correlated with poorer overall survival of patients compared to those with high expression of AGPS. In addition, AGPS can promote ferroptosis by modulating the function of peroxisome-resulting in the lower survival of prostate cancer cells. Furthermore, it was shown that AGPS can be ubiquitinated and degraded by the E3 ligase-MDM2 through the proteasomal pathway. Meanwhile, kinase TrkA can promote the combination of AGPS and MDM2 by phosphorylating AGPS at Y451 site. It was verified that kinase TrkA inhibitor—Larotrectinib can increase the susceptibility of prostate cancer cells to ferroptosis, which leads to the inhibition of prostate cancer proliferation to a great extent in vitro and in vivo.

Conclusion

Based on these findings, we proposed the combination of ferroptosis inducer and TrkA inhibitor to synergistically exert anti-tumor effects, which may provide a new strategy for the clinical treatment of prostate cancer.
Marinopyrrole derivative MP1 as a novel anti-cancer agent in group 3 MYC-amplified Medulloblastoma
Authors: Coulter Don W. , Chhonker Yashpal S. , Kumar Devendra , Kesherwani Varun , Aldhafiri Wafaa N. , McIntyre Erin M. , Alexander Gracey , Ray Sutapa , Joshi Shantaram S. , Li Rongshi , Murry Daryl J. , Chaturvedi Nagendra K.
Published: January 2024

Background

Medulloblastoma (MB) patients with MYC oncogene amplification or overexpression exhibit extremely poor prognoses and therapy resistance. However, MYC itself has been one of the most challenging targets for cancer treatment. Here, we identify a novel marinopyrrole natural derivative, MP1, that shows desirable anti-MYC and anti-cancer activities in MB.

Methods

In this study, using MYC-amplified (Group 3) and non-MYC amplified MB cell lines in vitro and in vivo, we evaluated anti-cancer efficacies and molecular mechanism(s) of MP1.

Results

MP1 significantly suppressed MB cell growth and sphere counts and induced G2 cell cycle arrest and apoptosis in a MYC-dependent manner. Mechanistically, MP1 strongly downregulated the expression of MYC protein. Our results with RNA-seq revealed that MP1 significantly modulated global gene expression and inhibited MYC-associated transcriptional targets including translation/mTOR targets. In addition, MP1 inhibited MYC-target metabolism, leading to declined energy levels. The combination of MP1 with an FDA-approved mTOR inhibitor temsirolimus synergistically inhibited MB cell growth/survival by downregulating the expression of MYC and mTOR signaling components. Our results further showed that as single agents, both MP1 and temsirolimus, were able to significantly inhibit tumor growth and MYC expression in subcutaneously or orthotopically MYC-amplified MB bearing mice. In combination, there were further anti-MB effects on the tumor growth and MYC expression in mice.

Conclusion

These preclinical findings highlight the promise of marinopyrrole MP1 as a novel MYC inhibition approach for MYC-amplified MB.
Risk-management decision-making data from a community-based sample of racially diverse women at high risk of breast cancer: rationale, methods, and sample characteristics of the Daughter Sister Mother Project survey
Authors: Padamsee Tasleem J. , Bijou Christina , Swinehart-Hord Paige , Hils Megan , Muraveva Anna , Meadows Rachel J. , Shane-Carson Kate , Yee Lisa D. , Wills Celia E. , Paskett Electra D.
Published: January 2024

Background

To understand the dynamics that limit use of risk-management options by women at high risk of breast cancer, there is a critical need for research that focuses on patient perspectives. Prior research has left important gaps: exclusion of high-risk women not in risk-related clinical care, exclusion of non-white populations, and lack of attention to the decision-making processes that underlie risk-management choices. Our objective was to create a more inclusive dataset to facilitate research to address disparities related to decision making for breast cancer risk management.

Methods

The Daughter Sister Mother Project survey collects comprehensive information about the experiences of women at high risk of breast cancer. We collected novel measures of feelings about and reactions to cancer screenings; knowledge, barriers, and facilitators of risk-management options; beliefs related to cancer risk and risk management; and involvement with loved ones who had cancer. Eligible individuals were non-Hispanic white and non-Hispanic Black adult women who self-identified as having high risk of breast cancer and had no personal history of cancer. Between October 2018 and August 2019, 1053 respondents completed the online survey. Of these, 717 were confirmed through risk prediction modeling to have a lifetime breast cancer risk of ≥ 20%. Sociodemographic characteristics of this sample were compared to those of nationally representative samples of the US population: the 2019 Health Information National Trends Survey and the Pew Research Center report: Jewish Americans in 2020.

Results

The sample of 717 women at objectively high risk of breast cancer was largely (95%) recruited from non-clinical sources. Of these respondents, only 31% had seen a genetic counselor, 34% had had genetic testing specific to breast cancer risk, and 35% had seen at least one breast or cancer care specialist. The sample includes 35% Black respondents and 8% with Ashkenazi Jewish ancestry. Although encompassing a substantial range of ages, incomes, and education levels, respondents are overall somewhat younger, higher-income, and more educated than the US population as a whole.

Conclusions

The DSM dataset offers comprehensive data from a community-based, diverse sample of women at high risk of breast cancer. The dataset includes substantial proportions of Black and Ashkenazi Jewish women and women who are not already in clinical care related to their breast cancer risk. This sample will facilitate future studies of risk-management behaviors among women who are and are not receiving high-risk care, and of variations in risk-management experiences across race and ethnicity.
Sertraline for anxiety in adults with a diagnosis of autism (STRATA): study protocol for a pragmatic, multicentre, double-blind, placebo-controlled randomised controlled trial
Authors: Rai Dheeraj , Webb Doug , Lewis Amanda , Cotton Leonora , Norris Jade Eloise , Alexander Regi , Baldwin David S. , Brugha Traolach , Cochrane Madeleine , Del Piccolo Maria Chiara , Glasson Emma J. , Hatch Katherine K. , Kessler David , Langdon Peter E. , Leonard Helen , MacNeill Stephanie J. , Mills Nicola , Morales Maximiliano Vazquez , Morgan Zoe , Mukherjee Raja , Realpe Alba X. , Russell Ailsa , Starkstein Sergio , Taylor Jodi , Turner Nicholas , Thorn Joanna , Welch Jack ,   on behalf of the STRATA autistic advisory group, Douglas Sarah , Hale Peter , O’Brien Sarah , Walker Amy , Wiles Nicola
Published: January 2024

Background

Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to manage anxiety in adults with an autism diagnosis. However, their effectiveness and adverse effect profile in the autistic population are not well known. This trial aims to determine the effectiveness and cost-effectiveness of the SSRI sertraline in reducing symptoms of anxiety and improving quality of life in adults with a diagnosis of autism compared with placebo and to quantify any adverse effects.

Methods

STRATA is a two-parallel group, multi-centre, pragmatic, double-blind, randomised placebo-controlled trial with allocation at the level of the individual. It will be delivered through recruiting sites with autism services in 4 regional centres in the United Kingdom (UK) and 1 in Australia. Adults with an autism diagnosis and a Generalised Anxiety Disorder Assessment (GAD-7) score ≥ 10 at screening will be randomised 1:1 to either 25 mg sertraline or placebo, with subsequent flexible dose titration up to 200 mg. The primary outcome is GAD-7 scores at 16 weeks post-randomisation. Secondary outcomes include adverse effects, proportionate change in GAD-7 scores including 50% reduction, social anxiety, obsessive-compulsive symptoms, panic attacks, repetitive behaviours, meltdowns, depressive symptoms, composite depression and anxiety, functioning and disability and quality of life. Carer burden will be assessed in a linked carer sub-study. Outcome data will be collected using online/paper methods via video call, face-to-face or telephone according to participant preference at 16, 24 and 52 weeks post-randomisation, with brief safety checks and data collection at 1–2, 4, 8, 12 and 36 weeks. An economic evaluation to study the cost-effectiveness of sertraline vs placebo and a QuinteT Recruitment Intervention (QRI) to optimise recruitment and informed consent are embedded within the trial. Qualitative interviews at various times during the study will explore experiences of participating and taking the trial medication.

Discussion

Results from this study should help autistic adults and their clinicians make evidence-based decisions on the use of sertraline for managing anxiety in this population.

Trial registration

ISRCTN, ISRCTN15984604. Registered on 08 February 2021. EudraCT 2019-004312-66. ANZCTR ACTRN12621000801819. Registered on 07 April 2021.
Personalizing the first dose of FSH for IVF/ICSI patients through machine learning: a non-inferiority study protocol for a multi-center randomized controlled trial
Authors: Correa Nuria , Cerquides Jesus , Arcos Josep Lluis , Vassena Rita , Popovic Mina
Published: January 2024

Background

Adequately selecting the initial follicle-stimulating hormone (FSH) dose during controlled ovarian stimulation (COS) is key for success in assisted reproduction. The objective of COS is to obtain an optimal number of oocytes to increase the chances of achieving a pregnancy, while avoiding complications for the patient. Current clinical protocols do achieve good results for the majority of patients, but further refinements in individualized FSH dosing may reduce the risk of poor ovarian response while also limiting the risk of ovarian hyperstimulation syndrome (OHSS) risk. Models to select the first FSH dose in COS have been presented in literature with promising results. However, most have only been developed and tested in normo-ovulatory women under the age of 40 years.

Methods

This is a randomized, controlled, multicenter, single blinded, clinical trial. This study will be performed in 236 first cycle in vitro fertilization (IVF) and/or ICSI (intracytoplasmic sperm injection) patients, randomized 1:1 in two arms. In the intervention arm, the dose of FSH will be assigned by a machine learning (ML) model called IDoser, while in the control arm, the dose will be determined by the clinician following standard practice. Stratified block randomization will be carried out depending on the patient being classified as expected low responder, high responder, or normo-responder. Patients will complete their participation in the trial once the first embryo transfer result is known. The primary outcome of the study is the number of metaphase II (MII) oocytes retrieved at ovarian pick up (OPU) and the hypothesis of non-inferiority of the intervention arm compared to the control. Secondary outcomes include the number of cycle cancelations (due to low response or no retrieval of mature oocytes), risk of ovarian hyperstimulation syndrome (OHSS), and clinical pregnancy and live birth rates per first transfer.

Discussion

To our knowledge, this is the first randomized trial to test clinical performance of an all-patient inclusive model to select the first dose of FSH for COS. Prospective trials for machine learning (ML) models in healthcare are scarce but necessary for clinical application.

Trial registration

ClinicalTrials.gov, NCT05948293. Registered on 14 July 2023.
Specific-cytokine associations with outcomes in knee osteoarthritis subgroups: breaking down disease heterogeneity with phenotyping
Authors: Calvet Joan , Berenguer-Llergo Antoni , Orellana Cristóbal , García-Manrique María , Rusiñol Menna , Garcia-Cirera Silvia , Llop Maria , Arévalo Marta , Garcia-Pinilla Alba , Galisteo Carlos , Aymerich Cristina , Gómez Rafael , Serrano Alejandra , Carreras Anna , Gratacós Jordi
Published: January 2024

Background

Despite existing extensive literature, a comprehensive and clinically relevant classification system for osteoarthritis (OA) has yet to be established. In this study, we aimed to further characterize four knee OA (KOA) inflammatory phenotypes (KOIP) recently proposed by our group, by identifying the inflammatory factors associated with KOA severity and progression in a phenotype-specific manner.

Methods

We performed an analysis within each of the previously defined four KOIP groups, to assess the association between KOA severity and progression and a panel of 13 cytokines evaluated in the plasma and synovial fluid of our cohort’s patients. The cohort included 168 symptomatic female KOA patients with persistent joint effusion.

Results

Overall, our analyses showed that associations with KOA outcomes were of higher magnitude within the KOIP groups than for the overall patient series (all p-values < 1.30e−16) and that several of the cytokines showed a KOIP-specific behaviour regarding their associations with KOA outcomes.

Conclusion

Our study adds further evidence supporting KOA as a multifaceted syndrome composed of multiple phenotypes with differing pathophysiological pathways, providing an explanation for inconsistencies between previous studies focussed on the role of cytokines in OA and the lack of translational results to date. Our findings also highlight the potential clinical benefits of accurately phenotyping KOA patients, including improved patient stratification, tailored therapies, and the discovery of novel treatments.
Identification of an ADME-related gene for forecasting the prognosis and responding to immunotherapy in sarcomas
Authors: Wang Jianlong , Wang Guowei , Hu Tianrui , Wang Hongyi , Zhou Yong
Published: January 2024

There are more than 170 subtypes of sarcomas (SARC), which pose a challenge for diagnosis and patient management. Relatively simple or complex karyotypes play an indispensable role in the early diagnosis and effective treatment of SARC. The genes related to absorption, distribution, metabolism, and excretion (ADME) of a drug can serve as prognostic biomarkers of cancer and potential drug targets. In this study, a risk score signature was created. The SARC cohort was downloaded from The Cancer Genome Atlas (TCGA) database, and divided into high-risk group and low-risk group according to the median value of risk score. Compared with high-risk group, low-risk group has a longer survival time, which is also verified in osteosarcoma cohort from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. In addition, the relationship between the signature and immunophenotypes, including status of immune cell infiltration and immune checkpoint expression, was explored. Then, we found that high-risk group is in immunosuppressive status. Finally, we verified that PPARD played a role as a carcinogen in osteosarcoma, which provided a direction for targeted treatment of osteosarcoma in the future. Generally speaking, the signature can not only help clinicians predict the prognosis of patients with SARC, but also provide a theoretical basis for developing more effective targeted drugs in the future.
Identification of potential crucial genes and therapeutic targets for epilepsy
Authors: Wang Shitao , Xie Zhenrong , Jun Tian , Ma Xuelu , Zhang Mengen , Rao Feng , Xu Hui , Lu Jinghong , Ding Xiangqian , Li Zongyou
Published: January 2024

Background

Epilepsy, a central neurological disorder, has a complex genetic architecture. There is some evidence suggesting that genetic factors play a role in both the occurrence of epilepsy and its treatment. However, the genetic determinants of epilepsy are largely unknown. This study aimed to identify potential therapeutic targets for epilepsy.

Methods

Differentially expressed genes (DEGs) were extracted from the expression profiles of GSE44031 and GSE1834. Gene co-expression analysis was used to confirm the regulatory relationship between newly discovered epilepsy candidate genes and known epilepsy genes. Expression quantitative trait loci analysis was conducted to determine if epilepsy risk single-nucleotide polymorphisms regulate DEGs’ expression in human brain tissue. Finally, protein–protein interaction analysis and drug–gene interaction analysis were performed to assess the role of DEGs in epilepsy treatment.

Results

The study found that the protein tyrosine phosphatase receptor-type O gene (PTPRO) and the growth arrest and DNA damage inducible alpha gene (GADD45A) were significantly upregulated in epileptic rats compared to controls in both datasets. Gene co-expression analysis revealed that PTPRO was co-expressed with RBP4, NDN, PAK3, FOXG1, IDS, and IDS, and GADD45A was co-expressed with LRRK2 in human brain tissue. Expression quantitative trait loci analysis suggested that epilepsy risk single-nucleotide polymorphisms could be responsible for the altered PTPRO and GADD45A expression in human brain tissue. Moreover, the protein encoded by GADD45A had a direct interaction with approved antiepileptic drug targets, and GADD45A interacts with genistein and cisplatin.

Conclusions

The results of this study highlight PTPRO and GADD45A as potential genes for the diagnosis and treatment of epilepsy.
Salsal: blockchain for vetting cultural object collections
Authors: Khelifi Adel , Altaweel Mark , Hashir Mohammad , Hadjitofi Tasoula , Ghazal Mohammad
Published: January 2024

Many modern cultural object collections suffer from the problem of being obtained in unethical and illegal circumstances. Additionally, information about collections, including their status, object descriptions, and other data need up-to-date information presented to users. We propose a novel blockchain tool called Salsal that enables the vetting of objects, individually or as part of more extensive collections, to meet required ethical and legal guidelines while informing users about relevant information regarding collections. Blockchain provides a better and more rapid way for users to know about collections using a decentralized and immutable ledger technology. Blockchain can be used to incentivize or even pressure collections to vet their objects for ethical and legal guidelines that can benefit the public who use object collections. The prototype software we have made is presented and compared to other blockchains, with code and demonstration provided. We present how our blockchain can enable benefit, providing a useful vetting process for cultural objects, and allowing a user community to contribute to collections in a transparent and secure manner.
Nonlinear dimensionality reduction based visualization of single-cell RNA sequencing data
Authors: Yousuff Mohamed , Babu Rajasekhara , Rathinam Anand
Published: January 2024

Single-cell multi-omics technology has catalyzed a transformative shift in contemporary cell biology, illuminating the nuanced relationship between genotype and phenotype. This paradigm shift hinges on the understanding that while genomic structures remain uniform across cells within an organism, the expression patterns dictate physiological traits. Leveraging high throughput sequencing, single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool, enabling comprehensive transcriptomic analysis at unprecedented resolution. This paper navigates through a landscape of dimensionality reduction techniques essential for distilling meaningful insights from the scRNA-seq datasets. Notably, while foundational, Principal Component Analysis may fall short of capturing the intricacies of diverse cell types. In response, nonlinear techniques have garnered traction, offering a more nuanced portrayal of cellular relationships. Among these, Pairwise Controlled Manifold Approximation Projection (PaCMAP) stands out for its capacity to preserve local and global structures. We present an augmented iteration, Compactness Preservation Pairwise Controlled Manifold Approximation Projection (CP-PaCMAP), a novel advancement for scRNA-seq data visualization. Employing benchmark datasets from critical human organs, we demonstrate the superior efficacy of CP-PaCMAP in preserving compactness, offering a pivotal breakthrough for enhanced classification and clustering in scRNA-seq analysis. A comprehensive suite of metrics, including Trustworthiness, Continuity, Mathew Correlation Coefficient, and Mantel test, collectively validate the fidelity and utility of proposed and existing techniques. These metrics provide a multi-dimensional evaluation, elucidating the performance of CP-PaCMAP compared to other dimensionality reduction techniques.
Minimum acceptable diet and associated factors among children aged 6–23 months in Jig-Jiga, Somali region, eastern Ethiopia, 2022
Authors: Farah Shukri , Derese Tariku , Abera Legesse
Published: January 2024

Background

The minimum acceptable diet is the proportion of children aged 6–23 months who consumed the minimum meal frequency and minimum dietary diversity during the previous day or night. The minimum acceptable diet assesses both micronutrient adequacy and the quantity of food consumed during the previous day or night. Inappropriate infant and young child feeding practices during this period result in significant threats to child health through impaired cognitive development. Therefore, this study aims to assess the minimum acceptable diet and associated factors among children aged 6–23 months in Jig-Jiga, Somali region, Eastern Ethiopia.

Methods

A community-based, cross-sectional study was conducted in Jig-Jiga town. A systematic random sampling technique was used to select 536 children aged 6–23 months with their mothers. Data were collected using a pre-tested, structured questionnaire. The data were entered into Epi-data 3.1. The data were cleaned and analyzed using SPSS v20. Bi-variable and multivariable logistic regression analyses were done, and model fitness was checked and tested by the Hosmer-Lemeshow goodness of fit test. The results of the adjusted odds ratio with 95% confidence intervals and P < 0.05 were considered statistically significant.

Result

The overall prevalence of a minimum acceptable diet was 47.2% (95% CI: 43.1–51.6). Occupation of fathers (AOR = 0.5, 95%CI: 0.3–0.8), child age of 6–11 months (AOR = 3.6, 95%CI: 1.7–7.7), age of the mother 15–24 years (AOR = 7.6, 95%CI: 1.5–38.146), 25–34 years (AOR = 5.56, 95%CI: 1.17–26.325), mothers who had only one under-five child (AOR = 2.1, 95%CI: 1.298–3.471), and media as a source of information (AOR = 0.16, 95%CI: 0.061–0.433) were associated with the minimum acceptable diet.

Conclusion

This study showed that the prevalence of a minimum acceptable diet was low. Factors associated with a minimum acceptable diet included the father’s occupation, the child’s age, the mother’s age, having one under-five child, and the media as a source of information. Therefore, interventional strategies that focus on family planning and advocacy for infant and young child feeding are required to improve the provision of a minimum acceptable diet.
Activity provider-facilitated patient and public involvement with care home residents
Authors: Micklewright Kerry , Killett Anne , Akdur Gizdem , Biswas Priti , Blades Pamela , Irvine Lisa , Jones Liz , Meyer Julienne , Ravenscroft Natalie , Woodhead Hilary , Goodman Claire
Published: January 2024

Background

In care home research, residents are rarely included in patient and public involvement and engagement (PPIE) despite their lived experiences of day-to-day care. This paper reports on a novel approach to PPIE, developed in response to Covid-19, and utilised in a large UK-based study focused on care homes. PPIE sessions were facilitated on behalf of the research team by Activity Providers (APs) already working within the care homes. This paper provides an account of how PPIE with care home residents can be achieved.

Methods

An exploratory design was used to see if it was possible to support “in-house” PPIE, with researchers working at a distance in partnership with care home staff. The National Activity Providers Association recruited five APs working in care homes. A series of optional discussion or activity sessions were developed by the research team in partnership with APs, tailored to reflect the research topics of interest and to make sessions accessible to residents with differing needs.

Results

APs facilitated four rounds of PPIE with up to 56 residents per topic, including individuals living with cognitive and communication impairments. Topics discussed included residents’ views on data use, measuring quality of life and the prioritisation of care-related data for study collection. Feedback from the residents was observed to have unexpected and positive changes to participating care homes’ practice. APs valued participation and working with researchers. They identified acquisition of new skills and insights into residents’ thoughts and preferences as direct benefits. Challenges included time pressures on APs and managing emotive feedback. APs were able to approach residents at times convenient to them and in ways that best suited their individual needs. PPIE with residents provided different perspectives, particularly with respect to the importance of different types of data, and constructive challenge about some of the research team’s assumptions.

Conclusions

PPIE with APs as research partners is a promising approach to working in an inclusive and participatory way with care home residents. The voices of older care home residents, including those living with cognitive or communicative impairments, are important for the successful and meaningful completion of research.
Choroidal measurements in decision making for retinopathy of prematurity: a decision tree analysis
Authors: Bahar Mohammadreza Mehrabi , Salari Farhad , Dastjanifarahani Afsar , Ghassemi Fariba , Harper C. Armitage , Bazvand Fatemeh
Published: January 2024

Background

To compare the choroidal thickness and vascular profile of premature infants with ROP (retinopathy of prematurity) using a handheld SD-OCT device.

Methods

We performed horizontal SD-OCT scans through the fovea in 115 eyes of 66 premature infants. Premature infants included 2 groups [infants with ROP requiring treatment (as treatment group) vs. infants without ROP or with ROP not- requiring treatment (as no-treatment group)] Choroidal thicknesses (CT) were measured at 5 points, including the fovea, 250 µm, and 500 µm mm nasal and temporal to the fovea. The choroidal vascularity index (CVI) and choroidal stromal index (CSI) were also calculated. The classification and regression tree (CRT) algorithm was used to predict the need for treatment based on all OCT characteristics.

Results

Mean CT was higher in 500 µm nasal to the fovea compared to temporal CT (275.8 ± 64.8 and 257.1 ± 57.07, P value < 0.03). No statistically significant difference was found regarding CVI, corrected CVI, and temporal and nasal CT in the treatment group versus the no-treatment group. The foveal CT was significantly lower in ROP patients with the plus disease compared to not-plus ROP (P value = 0.03. ANOVA, Bonferroni posthoc test). CT was not significantly different between plus and pre-plus patients (P-value = 0.9, ANOVA, Bonferroni posthoc test). No significant relationship was found between the stage of ROP and choroidal thickness (P value > 0.05, GEE). The decision tree analysis showed that in infants with ROP, the most important predictor for the need for treatment is CSI.

Conclusion

This study delineated the possible effectiveness of choroidal measurements as an additive to decision-making for ROP. We also demonstrated that choroidal involution is associated with the presence of plus disease, not with the stage of ROP. We demonstrated that choroidal measurements are very sensitive but not specific tools for assessing the need for treatment in ROP patients.
Financial Toxicity and Health-Related Quality of Life Profile of Patients With Hematologic Malignancies Treated in a Universal Health Care System
Authors: Sparano Francesco , Giesinger Johannes M. , Gaidano Gianluca , Anota Amelie , Cavo Michele , Brini Alberto , Voso Maria Teresa , Venditti Adriano , Perrone Francesco , Di Maio Massimo , Luppi Mario , Baron Frederic , Platzbecker Uwe , Fazi Paola , Vignetti Marco , Efficace Fabio
Published: January 2024

PURPOSE

We investigated the association of financial toxicity (FT) with the health-related quality of life (HRQoL) profile of patients with hematologic malignancies treated in a universal health care system.

METHODS

We did a secondary analysis of six multicenter studies enrolling patients with hematologic malignancies. FT was evaluated using the financial difficulties item of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Multivariable linear regression models were used to assess the mean differences in HRQoL scores between patients with or without FT, while adjusting for key potential confounding factors. We also examined the prevalence of clinically important problems and symptoms by the experience of FT, using established thresholds for the EORTC QLQ-C30. Multivariable binary logistic regression analysis was performed to explore the risk factors associated with FT.

RESULTS

Overall, 1,847 patients were analyzed, of whom 441 (23.9%) reported FT. We observed statistically and clinically relevant worse scores for patients with FT compared with those without FT for all the EORTC QLQ-C30 scales. The three largest clinically relevant mean differences between patients with and without FT were observed in pain (∆ = 19.6 [95% CI, 15.7 to 23.5]; P < .001), social functioning (∆ = –18.9 [95% CI, –22.5 to –15.2]; P < .001), and role functioning (Δ = –17.7 [95% CI, –22.1 to –13.3]; P < .001). Patients with FT tended to report a higher prevalence of clinically important problems and symptoms across all EORTC QLQ-C30 scales. In the univariable and multivariable analyses, the presence of FT was associated with the presence of comorbidities, an Eastern Cooperative Oncology Group performance status ≥1, and not receiving a salary.

CONCLUSION

Patients with hematologic malignancies treated in the setting of a universal health care system who experience FT have a worse HRQoL profile compared with those without FT.
A rheological model for spheroids including extra-cellular matrix
Authors: Verdier Claude , Palade Liviu I.
Published: January 2024

The rheology of spheroids has been studied intensively recently and it was shown that the presence of the Extra-Cellular Matrix (ECM) can have significant effects on the overall behaviour of these biological systems. Collagen I can indeed be a proxy between cells and bring new intriguing effects, as its content increases. To investigate these effects further, a two-phase emulsion model is proposed including interactions between cells and the ECM. Starting with the single cell and collagen individual viscoelastic properties, the model can be tested against previously obtained data for spheroids. The model has interesting features and capabilities for it covers a variety of behaviours and uses fitting parameters such as collagen and cell concentration, as well as adhesion energy. It is shown that the final intercellular collagen content can be large as compared to the initial one, and that this increase in collagen content induces a larger packing of cells, together with a larger adhesion energy.
Non-equilibrium attractor for non-linear stochastic dynamics
Authors: Patrón A. , Sánchez-Rey B. , Trizac E. , Prados A.
Published: January 2024

We study the dynamical behaviour of mesoscopic systems in contact with a thermal bath, described either via a non-linear Langevin equation at the trajectory level —or the corresponding Fokker-Planck equation for the probability distribution function at the ensemble level. Our focus is put on one-dimensional —or d-dimensional isotropic— systems in confining potentials, with detailed balance —fluctuation-dissipation thus holds, and the stationary probability distribution has the canonical form at the bath temperature. When quenching the bath temperature to low enough values, a far-from-equilibrium state emerges that rules the dynamics over a characteristic intermediate timescale. Such a long-lived state has a Dirac-delta probability distribution function and attracts all solutions over this intermediate timescale, in which the initial conditions are immaterial while the influence of the bath is still negligible. Numerical evidence and qualitative physical arguments suggest that the above picture extends to higher-dimensional systems, with anisotropy and interactions.
Microtubule polyglutamylation is an essential regulator of cytoskeletal integrity in Trypanosoma brucei
Authors: Jentzsch Jana , Wunderlich Hannes , Thein Marinus , Bechthold Julia , Brehm Lucas , Krauss Sebastian W. , Weiss Matthias , Ersfeld Klaus
Published: January 2024

Tubulin polyglutamylation, catalysed by members of the tubulin tyrosine ligase-like (TTLL) protein family, is an evolutionarily highly conserved mechanism involved in the regulation of microtubule dynamics and function in eukaryotes. In the protozoan parasite Trypanosoma brucei, the microtubule cytoskeleton is essential for cell motility and maintaining cell shape. In a previous study, we showed that T. brucei TTLL6A and TTLL12B are required to regulate microtubule dynamics at the posterior cell pole. Here, using gene deletion, we show that the polyglutamylase TTLL1 is essential for the integrity of the highly organised microtubule structure at the cell pole, with a phenotype distinct from that observed in TTLL6A- and TTLL12B-depleted cells. Reduced polyglutamylation in TTLL1-deficient cells also leads to increased levels in tubulin tyrosination, providing new evidence for an interplay between the tubulin tyrosination and detyrosination cycle and polyglutamylation. We also show that TTLL1 acts differentially on specific microtubule doublets of the flagellar axoneme, although the absence of TTLL1 appears to have no measurable effect on cell motility.