bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intra-ovarian inflammatory states and their associations with embryo quality in normal-BMI PCOS patients undergoing IVF treatment
Authors: Shang Jie , Wang Siyu , Wang Aiyuan , Li Fang , Zhang Jing , Wang Jin , Lv Rui , Chen Haixia , Mu Xiaohuan , Zhang Kai , Bai Xiaohong , Tian Ye 
Published: January 2024

Abstract
Background
Polycystic ovary syndrome (PCOS) is the main cause of anovulatory infertility in women of reproductive age, and low-grade chronic inflammation plays a key role in the occurrence and development of PCOS. However, obesity, as a likely confounding factor, can affect the inflammatory state of PCOS patients.

Objective
The aim of this study was to comprehensively investigate intra-ovarian inflammatory states and their impact on embryo quality in PCOS patients with a normal BMI undergoing IVF treatment.

Methods
DIA-mass spectrometry-based proteomics and bioinformatic analysis were combined to comprehensively profile the protein expression of granulosa cells (GCs) from 5 normal-BMI PCOS patients and 5 controls. Thirty-four cytokines were further systematically detected in follicular fluid (FF) from 32 age- and BMI-matched normal-BMI patients using Luminex liquid chip suspension technology. Next, the differentially expressed cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA) in 24 newly recruited subjects, and the relationship between these cytokines and embryo quality in PCOS patients was analysed. Finally, these cytokine levels were compared and evaluated in PCOS patients with different androgen levels.

Results
Proteomic analysis showed that the suppression of substance metabolism and steroid biosynthesis, more interestingly, resulted in an enhanced immune and inflammatory response in the GCs of normal-BMI PCOS patients and prompted the involvement of cytokines in this process. Luminex analysis further showed that FF macrophage inflammatory protein-1 beta (MIP-1β) and stromal cell-derived factor-1 alpha (SDF-1α) levels were significantly increased in normal-BMI PCOS patients compared to controls (P = 0.005; P = 0.035, respectively), and the ELISA results were consistent with these findings. Besides, FF MIP-1β showed an inverse correlation with the number of D3 good-quality embryos and the good-quality blastocyst rate in patients with PCOS (P = 0.006; P = 0.003, respectively), which remained significant after correction for multiple comparisons. Moreover, SDF-1α levels had no relationship with embryo development in PCOS patients. Additionally, SDF-1α levels were significantly lower in PCOS patients with high androgen levels than in controls (P = 0.031).

Conclusions
Local ovarian inflammation was present in normal-BMI PCOS patients, affecting follicular development, and FF MIP-1β may be a potential biomarker associated with embryo quality in normal-BMI PCOS patients.

Graphical abstract
Comparative analysis of hippocampal extracellular space uncovers widely altered peptidome upon epileptic seizure in urethane-anaesthetized rats
Authors: Tukacs Vanda , Mittli Dániel , Hunyadi-Gulyás Éva , Darula Zsuzsanna , Juhász Gábor , Kardos József , Kékesi Katalin Adrienna 
Published: January 2024

Abstract
Background
The brain extracellular fluid (ECF), composed of secreted neurotransmitters, metabolites, peptides, and proteins, may reflect brain processes. Analysis of brain ECF may provide new potential markers for synaptic activity or brain damage and reveal additional information on pathological alterations. Epileptic seizure induction is an acute and harsh intervention in brain functions, and it can activate extra- and intracellular proteases, which implies an altered brain secretome. Thus, we applied a 4-aminopyridine (4-AP) epilepsy model to study the hippocampal ECF peptidome alterations upon treatment in rats.

Methods
We performed in vivo microdialysis in the hippocampus for 3–3 h of control and 4-AP treatment phase in parallel with electrophysiology measurement. Then, we analyzed the microdialysate peptidome of control and treated samples from the same subject by liquid chromatography-coupled tandem mass spectrometry. We analyzed electrophysiological and peptidomic alterations upon epileptic seizure induction by two-tailed, paired t-test.

Results
We detected 2540 peptides in microdialysate samples by mass spectrometry analysis; and 866 peptides—derived from 229 proteins—were found in more than half of the samples. In addition, the abundance of 322 peptides significantly altered upon epileptic seizure induction. Several proteins of significantly altered peptides are neuropeptides (Chgb) or have synapse- or brain-related functions such as the regulation of synaptic vesicle cycle (Atp6v1a, Napa), astrocyte morphology (Vim), and glutamate homeostasis (Slc3a2).

Conclusions
We have detected several consequences of epileptic seizures at the peptidomic level, as altered peptide abundances of proteins that regulate epilepsy-related cellular processes. Thus, our results indicate that analyzing brain ECF by in vivo microdialysis and omics techniques is useful for monitoring brain processes, and it can be an alternative method in the discovery and analysis of CNS disease markers besides peripheral fluid analysis.
Fabry App: the value of a portable technology in recording day-to-day patient monitored information in patients with Fabry disease
Authors: D’Amore Simona , Mckie Mark , Fahey Andrew , Bleloch David , Grillo Giuseppina , Hughes Michael , Ramaswami Uma 
Published: January 2024

Abstract
Background
Fabry disease is a rare inherited disorder resulting from deficient α-galactosidase A enzyme activity. Common disease manifestations are sweating abnormalities, neuropathic pain, gastrointestinal symptoms and fatigue. Challenges are faced by health care professionals in evaluating symptom burden in the current clinical setting, and the demand for alternative methods for monitoring disease-specific symptoms has seen an acceleration in recent years. Smartphone technologies offer the potential for continuity of care and surveillance. As a part of a quality improvement project, a disease specific app was developed in collaboration with a software company (Health Touch Ltd) and made available for patient use in May 2018. The Fabry mobile app records five categories: pain, gastrointestinal symptoms, sweating, activity levels, medications. Fabry disease patients with gastrointestinal and pain symptoms attending the Lysosomal Storage Disorders Unit of the Royal Free London NHS Foundation Trust were reviewed to assess eligibility and invited to download the app for recording their symptoms (activity, sweating, pain and gastrointestinal) and medications. Patient-generated data were transmitted to a secure website for clinicians to review.

Results
One-hundred and thirty-nine symptomatic Fabry disease patients who had a smartphone (iPhone or android) were invited to download the app. Sixty-seven patients (26 males and 41 females; median age, 49 years [range, 20–81]) downloaded and tracked the Fabry App at least once. The median frequency of use per patient was 6 (range, 1–629). Pain in the hands and abdominal pain were significantly higher (p = 0.009 and p = 0.007, respectively) in patients with classic phenotype compared with patients with non-classic phenotypes.

Conclusions
We demonstrated the feasibility and acceptability of a smartphone app to facilitate the remote assessment and monitoring of Fabry disease symptom burden on a daily/weekly basis, as an alternative to the current standard of care that requires patients to recall their symptoms during 6 to 12 monthly annual clinic visits. Patients who were more likely to use the app had greater disease burden. This innovation has the potential to assess disease progression, early therapeutic intervention, thereby decreasing the burden of morbidity and mortality among Fabry patients, and to record long-term effects of Fabry-specific therapies.
Optimization of a recombinant BlaR-CTD protein formulation using the response surface methodology
Authors: Abdolvahab Mohadeseh Haji , Safari Mojdeh , Hasannejad Farkhonde , Asefi Nika , Salimi Alireza , Nazari Mahboobeh 
Published: January 2024

AbstractThe sequence of a carboxy-terminal of the β-lactam sensor-transducer protein (BlaR-CTD) from Bacillus licheniformis ATCC14580 was extracted from US7745193B2 patent and expressed in E. coli using pColdI vector as a soluble His-tag recombinant protein. In this study, several excipients were used to improve the stability of recombinant BlaR-CTD and obtain the optimal formulation for this protein using response surface methodology (RSM)/ Central Composite Design (CCD). Total protein concentration was measured by UV spectroscopy and the Bradford test. A total of 7 various factors were designed using four different excipients including Glycerol, Sucrose, Triton x-100, and Tween-20, and three different buffers like Tris, Borate, and PBS. By obtaining suitable excipients and buffer i.e. glycerol and sucrose, pH ranging from 7 to 9 were evaluated. The pH 7.62, glycerol 15.35%, and sucrose 152.52 mM were determined as the most suitable for improving the thermal stability of recombinant BlaR-CTD.
Gut mycobiome dysbiosis after sepsis and trauma
Authors: Park Gwoncheol , Munley Jennifer A. , Kelly Lauren S. , Kannan Kolenkode B. , Mankowski Robert T. , Sharma Ashish , Upchurch Gilbert , Casadesus Gemma , Chakrabarty Paramita , Wallet Shannon M. , Maile Robert , Bible Letitia E. , Wang Bo , Moldawer Lyle L. , Mohr Alicia M. , Efron Philip A. , Nagpal Ravinder 
Published: January 2024

Abstract
Background
Sepsis and trauma are known to disrupt gut bacterial microbiome communities, but the impacts and perturbations in the fungal (mycobiome) community after severe infection or injury, particularly in patients experiencing chronic critical illness (CCI), remain unstudied.

Methods
We assess persistence of the gut mycobiome perturbation (dysbiosis) in patients experiencing CCI following sepsis or trauma for up to two-to-three weeks after intensive care unit hospitalization.

Results
We show that the dysbiotic mycobiome arrays shift toward a pathobiome state, which is more susceptible to infection, in CCI patients compared to age-matched healthy subjects. The fungal community in CCI patients is largely dominated by Candida spp; while, the commensal fungal species are depleted. Additionally, these myco-pathobiome arrays correlate with alterations in micro-ecological niche involving specific gut bacteria and gut-blood metabolites.

Conclusions
The findings reveal the persistence of mycobiome dysbiosis in both sepsis and trauma settings, even up to two weeks post-sepsis and trauma, highlighting the need to assess and address the increased risk of fungal infections in CCI patients.

Graphical Abstract
Prognostic value of baseline neutrophil/lymphocyte ratio in HER2-positive metastatic breast cancer: exploratory analysis of data from the CLEOPATRA trial
Authors: Ding Nianhua , Pang Jian , Liu Xuan , He Xiongbin , Zhou Wei , Xie Haiqing , Feng Jianqi , Wang Guo , Tang Jie , Cao Jing , He Liying , He Yingjian , Wang Shouman , Xiao Zhi 
Published: January 2024

Abstract
Purpose
This study aimed to evaluate the prognostic role of the baseline neutrophil/lymphocyte ratio (NLR) in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab/pertuzumab.

Experimental design
Data from 780 patients from the CLEOPATRA trial and 248 local patients were collected. Patients were divided into the low and high NLR subgroups by the NLR cutoff value. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) methods were used to control bias. Associations between the NLR and progression-free survival (PFS) and overall survival (OS) were analyzed.

Results
The baseline characteristics of the subgroups were well balanced after PSM and IPTW. A low baseline NLR was associated with better PFS and OS in the trastuzumab and docetaxel (TH) group in the unadjusted, PSM and IPTW models. After IPTW, a low NLR, versus a high NLR, was associated with improved PFS (HR 1.35, 95% CI 1.07–1.70, P = 0.012) and OS (HR 1.47, 95% CI 1.12–1.94, P = 0.006) in the TH group. In patients undergoing treatment with trastuzumab and pertuzumab and docetaxel (THP), a low baseline NLR was also correlated with better PFS but not OS across the three models. After IPTW, a low NLR was associated with better PFS (HR 1.52, 95% CI 1.20–1.93, P = 0.001) than a high NLR in the THP group. Multivariate analyses showed that a low baseline NLR was a predictor for PFS and OS in the TH group and for PFS in the THP group in all three models. In the real-world setting, a low baseline NLR was a predictor of better PFS among patients treated with docetaxel plus trastuzumab without or with pertuzumab in the multivariate model (P = 0.015 and 0.008, respectively).

Conclusions
A low baseline NLR is associated with better survival outcomes among HER2-positive MBC patients receiving docetaxel plus trastuzumab/pertuzumab as first-line therapy.
Delivering COVID-19 vaccine trials at speed: the implementation of a phase IV UK multi-centre randomised controlled trial to determine safety and immunogenicity of COVID-19 vaccines co-administered with seasonal influenza vaccines (ComFluCOV)
Authors: Baos Sarah , Todd Rachel , Thirard Russell , Harris Rosie , Kirwan Jana , Joyce Katherine , Hutton David , Finn Adam , Clout Madeleine , Cappel-Porter Heike , Rogers Chris A , Lazarus Rajeka , Culliford Lucy 
Published: January 2024

Abstract
Background
In February 2021, the UK Department of Health and Social Care sought evidence on the safety and immunogenicity of COVID-19 and influenza vaccine co-administration to inform the 2021/2022 influenza vaccine policy. Co-administration could support vaccine uptake and reduce healthcare appointments. ComFluCOV was a randomised controlled trial designed to provide this evidence. This report outlines the methods used to deliver the trial in 6 months to answer an urgent public health question as part of the COVID-19 pandemic response.

Methods
ComFluCOV was commissioned by the Department of Health and Social Care and was managed by the Bristol Trials Centre, a UK-registered clinical trials unit. It was classed as an Urgent Public Health trial which facilitated fast-track regulatory approvals. Trial materials and databases were developed using in-house templates and those used in other COVID-19 vaccine trials. Participants were recruited by advertising, and via a trial website. Electronic trial systems enabled daily review of participant data. Weekly virtual meetings were held with stakeholders and trial sites.

Results
ComFluCOV was delivered within 6 months from inception to reporting, and trial milestones to inform the Department of Health and Social Care policy were met. Set-up was achieved within 1 month. Regulators provided expedited reviews, with feedback ahead of submission. Recruitment took place at 12 sites. Over 380 site staff were trained. Overall, 679 participants were recruited in two months. The final report to the Department of Health and Social Care was submitted in September 2021, following a preliminary safety report in May 2021. Trial results have been published.

Conclusion
The rapid delivery of ComFluCOV was resource intensive. It was made possible in part due to a unique set of circumstances created by the pandemic situation including measures put in place to support urgent public health research and public support for COVID-19 vaccine research. Elements of the trial could be adopted to increase efficiency in ‘non-pandemic’ situations including working with a clinical trials unit to enable immediate mobilisation of a team of experienced researchers, greater sharing of resources between clinical trials units, use of electronic trial systems and virtual meetings.

Trial registration
ISRCTN14391248, submitted on 17/03/2021. Registered on 30/03/2021.
Gentiopicroside inhibits the progression of gastric cancer through modulating EGFR/PI3K/AKT signaling pathway
Authors: Chen Qishuai , Zhang Tongtong , Li Bingjun , Zhu Zhenguo , Ma Xiaomin , Zhang Yun , Li Linchuan , Zhu Jiankang , Zhang Guangyong 
Published: January 2024

Abstract
Background
This study was designed to clarify the function and potential mechanism of gentiopicroside (GPS) in regulating the malignant progression of gastric cancer (GC) through in vitro cellular experiments and in vivo animal models.

Methods
AGS and HGC27 cells were divided into control group and GPS treatment groups (50 µM and 100 µM). Then, the cellular proliferation, colony formation, migration, invasion, and apoptosis were detected, respectively. Transmission electron microscope (TEM) was used to observe the mitochondrial changes, and the mitochondrial membrane potential (MMP) was determined using the JC-1 commercial kit. Network pharmacology analysis was utilized to screen the potential molecule that may be related to the GPS activity on GC cells, followed by validation tests using Western blot in the presence of specific activator. In addition, xenografted tumor model was established using BALB/c nude mice via subcutaneous injection of HGC27 cells, along with pulmonary metastasis model. Then, the potential effects of GPS on the tumor growth and metastasis were detected by immunohistochemistry (IHC) and HE staining.

Results
GPS inhibited the proliferation, invasion and migration of GC cell lines in a dose-dependent manner. Besides, it could induce mitochondrial apoptosis. Epidermal growth factor receptor (EGFR) may be a potential target for GPS action in GC by network pharmacological analysis. GPS inhibits activation of the EGFR/PI3K/AKT axis by reducing EGFR expression. In vivo experiments indicated that GPS induced significant decrease in tumor volume, and it also inhibited the pulmonary metastasis. For the safety concerns, GPS caused no obvious toxicities to the heart, liver, spleen, lung and kidney tissues. IHC staining confirmed GPS downregulated the activity of EGFR/PI3K/AKT.

Conclusions
Our investigation demonstrated for the first time that GPS could inhibit GC malignant progression by targeting the EGFR/PI3K/AKT signaling pathway. This study indicated that GPS may be serve as a safe anti-tumor drug for further treatment of GC.
Investigation of the effect of Jacobson’s relaxation technique on the fatigue of family caregivers of hemodialysis patients: a single-blinded randomized controlled trial
Authors: Sajadi Seyedeh Azam , Ravash Farzaneh , Farsi Zahra 
Published: January 2024

Abstract
Background
Caring for hemodialysis patients could be a heavy burden on family caregivers, causing them to become fatigued and decrease their quality of life. This study aimed to investigate whether Jacobson’s relaxation can help alleviate the fatigue of family caregivers of hemodialysis patients.

Methods
This randomized controlled trial was conducted in 2021. Sixty-six family caregivers of hemodialysis patients were recruited by convenience sampling from a referral hospital in Tehran, Iran, and assigned randomly by coin toss to two groups of experimental (n = 32) and control (n = 34). Caregivers in the experimental group performed Jacobson’s relaxation three times a week, each time for 30–45 min, for 30 days. The score and severity of fatigue before, 2 weeks after, and 1 month after the intervention were measured with the Fatigue Severity Scale. Data analysis was performed in the statistics software SPSS using descriptive statistics (frequency, percentage, mean, and standard deviation) and analytic statistics (Independent Samples t-test, Mann–Whitney U test, Chi-Square test, Fisher’s exact test, and RM-ANOVA test). The significance level was less than 0.05.

Results
The fatigue scores of the experimental and control groups were not significantly different before the intervention (4.42 ± 0.42 vs. 4.38 ± 0.42, P = 0.696). However, the experimental group had significantly lower fatigue scores than the control group 2 weeks after the intervention (4.11 ± 0.63 vs. 4.39 ± 0.42, P = 0.036) and 1 month after the intervention (3.5 ± 0.71 vs. 4.4 ± 0.44, P = 0.001). The results also showed a significant drop in the fatigue score of the experimental group after the intervention (P < 0.0001), but no such change in the control group (P = 0.662).

Conclusion
Jacobson’s relaxation technique was effective in alleviating the fatigue of family caregivers of hemodialysis patients. Nurses are therefore recommended to promote the technique as a safe and easy method of fatigue management for family caregivers.
“A bit lost”—Living with attention deficit hyperactivity disorder in the transition between adolescence and adulthood: an exploratory qualitative study
Authors: Rasmussen Inger Lise , Schei Jorun , Ørjasæter Kristin B. 
Published: January 2024

Abstract
Background
Attention deficit hyperactivity disorder (ADHD) begins in childhood and in many cases persists into adulthood. The transition from adolescence to adulthood for young people with ADHD is a vulnerable time and can be associated with comorbid conditions and unfavorable outcomes. Thus, further studies are needed to explore the characteristics of the transition period in emerging adulthood. The overall aim of this study was to gain increased knowledge of emerging adults’ experience of living with ADHD in the transition from adolescence to adulthood. This is a follow-up from a previous qualitative study that examined how young people experience receiving and living with a diagnosis of ADHD.

Method
The study has a qualitative retrospective design. Seven participants were included in this study using a purposive sampling method. We re-invited the same participants who were interviewed in 2015–2016 and conducted in-depth interviews. The data were subjected to Malterud’s systematic text condensation (STC).

Results
Four crosscutting themes were identified from our analysis: (1) low level of knowledge about ADHD and treatment options; (2) barriers to seeking and accessing help; (3) developing self-help strategies; and (4) a preference to discontinued medication use.

Conclusion
The participants emphasized a need for more information about ADHD in transition phases and support, both from professionals and peers, about finding ways to live meaningful lives. The treatment they had been offered was particularly linked to symptom reduction and medication use. A more appropriate focus would have been linked to how they, as citizens, could gain knowledge and skills to live meaningful lives with ADHD.