bluuebunny/crossref_metadata_2025_split huggingface dataset:
The aging ovary impairs acute stroke outcomes
Authors: Branyan Taylor E. , Aleksa Jocelyn , Lepe Esteban , Kosel Kelby , Sohrabji Farida 
Published: July 2023

AbstractIn experimental stroke, ovariectomized (OVX) adult rats have larger infarct volumes and greater sensory-motor impairment as compared to ovary-intact females and is usually interpreted to indicate that ovarian hormones are neuroprotective for stroke. Previous work from our lab shows that middle-aged, acyclic reproductively senescent (RS) females have worse stroke outcomes as compared to adult (normally cycling) females. We hypothesized that if loss of ovarian estrogen is the critical determinant of stroke outcomes, then ovary-intact middle-aged acyclic females, who have reduced levels of estradiol, should have similar stroke outcomes as age-matched OVX. Instead, the data demonstrated that OVX RS animals showed better sensory-motor function after stroke and reduced infarct volume as compared to ovary-intact females. Inflammatory cytokines were decreased in the aging ovary after stroke as compared to non-stroke shams, which led to the hypothesis that immune cells may be extravasated from the ovaries post-stroke. Flow cytometry indicated reduced overall T cell populations in the aging ovary after middle cerebral artery occlusion (MCAo), with a paradoxical increase in regulatory T cells (Tregs) and M2-like macrophages. Moreover, in the brain, OVX RS animals showed increased Tregs, increased M2-like macrophages, and increased MHC II + cells as compared to intact RS animals, which have all been shown to be correlated with better prognosis after stroke. Depletion of ovary-resident immune cells after stroke suggests that there may be an exaggerated response to ischemia and possible increased burden of the inflammatory response via extravasation of these cells into circulation. Increased anti-inflammatory cells in the brain of OVX RS animals further supports this hypothesis. These data suggest that stroke severity in aging females may be exacerbated by the aging ovary and underscore the need to assess immunological changes in this organ after stroke.
Pharmacotherapies of NAFLD: updated opportunities based on metabolic intervention
Authors: Shao Yaodi , Chen Suzhen , Han Liu , Liu Junli 
Published: July 2023

AbstractNon-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that is becoming increasingly prevalent, and it ranges from simple steatosis to cirrhosis. However, there is still a lack of pharmacotherapeutic strategies approved by the Food and Drug Administration, which results in a higher risk of death related to carcinoma and cardiovascular complications. Of note, it is well established that the pathogenesis of NAFLD is tightly associated with whole metabolic dysfunction. Thus, targeting interconnected metabolic conditions could present promising benefits to NAFLD, according to a number of clinical studies. Here, we summarize the metabolic characteristics of the development of NAFLD, including glucose metabolism, lipid metabolism and intestinal metabolism, and provide insight into pharmacological targets. In addition, we present updates on the progresses in the development of pharmacotherapeutic strategies based on metabolic intervention globally, which could lead to new opportunities for NAFLD drug development.
Optimal fractionation and timing of weekly cone-beam CT in daily surface-guided radiotherapy for breast cancer
Authors: Peng Haiyan , Yang Han , Lei Jinyan , Dai Xinyao , Cao Panpan , Jin Fu , Luo Huanli 
Published: July 2023

Abstract
Purpose
Surface-guided radiotherapy (SGRT) has been demonstrated to be a promising supplement to cone-beam computed tomography (CBCT) in adjuvant breast cancer radiotherapy, but a rational combination mode is lacking in clinical practice. The aim of this study was to explore this mode and investigate its impact on the setup and dose accuracy.

Methods and materials
Daily SGRT and weekly CBCT images were acquired for 23 patients with breast cancer who received conventional fractionated radiotherapy after lumpectomy. Sixteen modes were acquired by randomly selecting one (CBCT1), two (CBCTij), three (CBCTijk), four (CBCTijkl), and five (CBCT12345) images from the CBCT images for fusion with the SGRT. The CTV-PTV margins, OAR doses, and dose coverage (V95%) of PTV and CTV was calculated based on SGRT setup errors with different regions of interest (ROIs). Dose correlations between these modalities were investigated using Pearson and Spearman’s methods. Patient-specific parameters were recorded to assess their impact on dose.

Results
The CTV-PTV margins decreased with increasing CBCT frequencies and were close to 5 mm for CBCTijkl and CBCT12345. For the ipsilateral breast ROI, SGRT errors were larger in the AP direction, and target doses were higher in all modes than in the whole breast ROI (P < 0.05). In the ipsilateral ROI, the target dose correlations between all modes increased with increasing CBCT time intervals, decreased, and then increased with increasing CBCT frequencies, with the inflection point being CBCT participation at week 5. The dose deviations in CBCT123, CBCT124, CBCT125, CBCTijkl, and CBCT12345 were minimal and did not differ significantly (P > 0.05). There was excellent agreement between CBCT124 and CBCT1234, and between (CBCTijkl, CBCT12345) and CBCT125 in determining the classification for the percentage of PTV deviation (Kappa = 0.704–0.901). In addition, there were weak correlations between the patient’s Dips_b (ipsilateral breast diameter with bolus) and CTV doses in modes with CBCT participation at week 4 (R = 0.270 to 0.480).

Conclusions
Based on weekly CBCT, these modes with ipsilateral ROI and a combination of daily SGRT and a CBCT frequency of ≥ 3 were recommended, and CBCT was required at weeks 1 and 2 for CBCTijk.
Effectiveness of the Gratuité user fee exemption policy on utilization and outcomes of maternal, newborn and child health services in conflict-affected districts of Burkina Faso from 2013 to 2018: a pre-post analysis
Authors: Offosse Marie-Jeanne , Avoka Cephas , Yameogo Pierre , Manli Astrid Raissa , Goumbri Aude , Eboreime Ejemai , Boxshall Matt , Banke-Thomas Aduragbemi 
Published: July 2023

Abstract
Background
Evidence on effectiveness of user fee exemption policies targeting maternal, newborn, and child health (MNCH) services is limited for conflict-affected settings. In Burkina Faso, a country that has had its fair share of conflicts, user fee exemption policies have been piloted since 2008 and implemented along with a national government-led user fee reduction policy (‘SONU’: Soins Obstétricaux et Néonataux d'Urgence). In 2016, the government transitioned the entire country to a user fee exemption policy known as Gratuité. Our study objective was to assess the effect of the policy on the utilization and outcomes of MNCH services in conflict-affected districts of Burkina Faso.

Methods
We conducted a quasi-experimental study comparing four conflict-affected districts which had the user fee exemption pilot along with SONU before transitioning to Gratuité (comparator) with four other districts with similar characteristics, which had only SONU before transitioning (intervention). A difference-in-difference approach was initiated using data from 42 months before and 30 months after implementation. Specifically, we compared utilization rates for MNCH services, including antenatal care (ANC), facility delivery, postnatal care (PNC) and consultation for malaria. We reported the coefficient, including a 95% confidence interval (CI), p value, and the parallel trends test.

Results
Gratuité led to significant increases in rates of 6th day PNC visits for women (Coeff 0.15; 95% CI 0.01–0.29), new consultations in children < 1 year (Coeff 1.80; 95% CI 1.13–2.47, p < 0.001), new consultations in children 1–4 years (Coeff 0.81; 95% CI 0.50–1.13, p = 0.001), and uncomplicated malaria cases treated in children < 5 years (Coeff 0.59; 95% CI 0.44–0.73, p < 0.001). Other service utilization indicators investigated, including ANC1 and ANC5+ rates, did not show any statistically significant positive upward trend. Also, the rates of facility delivery, 6th hour and 6th week postnatal visits were found to have increased more in intervention areas compared to control areas, but these were not statistically significant.

Conclusions
Our study shows that, even in conflict-affected areas, the Gratuité policy significantly influences MNCH service utilization. There is a strong case for continued funding of the user fee exemption policy to ensure that gains are not reversed, especially if the conflict ceases to abate.
HiCognition: a visual exploration and hypothesis testing tool for 3D genomics
Authors: Langer Christoph C. H. , Mitter Michael , Stocsits Roman R. , Gerlich Daniel W. 
Published: July 2023

AbstractGenome browsers facilitate integrated analysis of multiple genomics datasets yet visualize only a few regions at a time and lack statistical functions for extracting meaningful information. We present HiCognition, a visual exploration and machine-learning tool based on a new genomic region set concept, enabling detection of patterns and associations between 3D chromosome conformation and collections of 1D genomics profiles of any type. By revealing how transcription and cohesion subunit isoforms contribute to chromosome conformation, we showcase how the flexible user interface and machine learning tools of HiCognition help to understand the relationship between the structure and function of the genome.
Alterations in the hepatocyte epigenetic landscape in steatosis
Authors: Maji Ranjan Kumar , Czepukojc Beate , Scherer Michael , Tierling Sascha , Cadenas Cristina , Gianmoena Kathrin , Gasparoni Nina , Nordström Karl , Gasparoni Gilles , Laggai Stephan , Yang Xinyi , Sinha Anupam , Ebert Peter , Falk-Paulsen Maren , Kinkley Sarah , Hoppstädter Jessica , Chung Ho-Ryun , Rosenstiel Philip , Hengstler Jan G. , Walter Jörn , Schulz Marcel H. , Kessler Sonja M. , Kiemer Alexandra K. 
Published: July 2023

AbstractFatty liver disease or the accumulation of fat in the liver, has been reported to affect the global population. This comes with an increased risk for the development of fibrosis, cirrhosis, and hepatocellular carcinoma. Yet, little is known about the effects of a diet containing high fat and alcohol towards epigenetic aging, with respect to changes in transcriptional and epigenomic profiles. In this study, we took up a multi-omics approach and integrated gene expression, methylation signals, and chromatin signals to study the epigenomic effects of a high-fat and alcohol-containing diet on mouse hepatocytes. We identified four relevant gene network clusters that were associated with relevant pathways that promote steatosis. Using a machine learning approach, we predict specific transcription factors that might be responsible to modulate the functionally relevant clusters. Finally, we discover four additional CpG loci and validate aging-related differential CpG methylation. Differential CpG methylation linked to aging showed minimal overlap with altered methylation in steatosis.
Remote cardiac rehabilitation program during the COVID-19 pandemic for patients with stable coronary artery disease after percutaneous coronary intervention: a prospective cohort study
Authors: Gu Junjie , Tong Xiaoshan , Meng Shasha , Xu Shuhui , Huang Jinyan 
Published: July 2023

Abstract
Objective
The coronavirus disease-19 (COVID-19) pandemic restricts rapid implementation of in-person delivery of cardiac rehabilitation (CR) at the center for coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI), thus enabling a cohort comparison of in-person vs. remote CR program. This study aims to investigate outcomes of exercise capacity, health-related quality of life (HRQL), mental health, and family burden of stable CAD patients undergoing PCI in low-to-moderate risk after different delivery models of CR program.

Methods
The study included a cohort of stable CAD patients undergoing PCI who had experienced two naturally occurring modes of CR program after hospital discharge at two time periods, January 2019 to December 2019 (in-person CR program) and May 2020 to May 2021 (remote CR program). The exercise capacity was assessed by means of 6-min walk test (6MWT), maximal oxygen uptake (VO2max) and the respiratory anaerobic threshold (VO2AT) before discharge, at the end of the 8-week and 12-week in-person or remote CR program after discharge.

Results
No adverse events occurred during the CR period. CAD patients had a longer distance walked in 6 min with a higher VO2max after 8-week and 12-week CR program whether in-person or remote model (p < 0.05). The distance walked in 6 min was longer and the maximal oxygen uptake (VO2max) was higher at the end of the 12-week in-person or remote CR program than 8-week in-person or remote CR program (p < 0.05). The respiratory anaerobic threshold (VO2AT) of CAD patients was decreased after 8-week CR program whether in-person or remote model (p < 0.05). CAD patients receiving remote CR program exhibited higher HRQL scores in domains of vitality (p = 0.048), role emotional (p = 0.039), mental health (p = 0.014), and the summary score of the mental composite (p = 0.048) compared to in-person CR program after 8 weeks. The anxiety and depression scores of CAD patients undergoing PCI were decreased after 8-week CR program whether in-person or remote model (p < 0.05). The CAD patients receiving remote delivery showed lower anxiety and depression scores compared to those receiving in-person delivery at the end of the 8-week CR program (p < 0.05). It was found that the family burden scores of CAD patients undergoing PCI were reduced after 8-week and 12-week CR program whether in-person or remote model (p < 0.05). The CAD patients receiving remote CR program showed lower family burden scores than those receiving in-person CR program after whether 8 weeks or 12 weeks (p < 0.05).

Conclusion
These data indicate that a properly designed and monitored remote delivery represents a feasible and safe model for low-to-moderate-risk, stable CAD patients undergoing PCI inaccessible to in-person CR during the COVID-19 pandemic.
CTLA4 DNA methylation is associated with CTLA-4 expression and predicts response to immunotherapy in head and neck squamous cell carcinoma
Authors: Hoffmann Friederike , Franzen Alina , de Vos Luka , Wuest Lennert , Kulcsár Zsófi , Fietz Simon , Maas Alexander Philippe , Hollick Sarah , Diop Marie Yatou , Gabrielpillai Jennis , Vogt Timo , Kuster Pia , Zarbl Romina , Dietrich Joern , Kristiansen Glen , Brossart Peter , Landsberg Jennifer , Strieth Sebastian , Dietrich Dimo 
Published: July 2023

Abstract
Background
The majority of patients with recurrent or metastasized head and neck squamous cell carcinoma (HNSCC) do not benefit from immune checkpoint blockade (ICB) while several patients experience severe and persistent immune-mediated side effects. Therefore, predictive biomarkers are urgently needed to allow for a personalized treatment. In this study, we investigated DNA methylation of the immune checkpoint gene CTLA4 with regard to its predictive value.

Methods
We analyzed CTLA4 promoter methylation in tumors of HNSCC patients (N = 29) treated with ICB at the University Medical Center Bonn with regard to response to ICB and progression-free survival. We further analyzed a second cohort (N = 138) of patients that did not receive ICB with regard to CTLA4 promoter methylation, CTLA-4 protein expression, and immune cell infiltrates. Finally, we tested inducibility of CTLA-4 protein expression in HNSCC cells using the DNA methyltransferase inhibitor decitabine.

Results
Lower CTLA4 promoter methylation correlated with response to ICB and prolonged progression-free survival. We could show that not only tumor infiltrating immune cells, but also HNSCC cells harbor cytoplasmic and nuclear CTLA-4 expression. CTLA4 promoter methylation inversely correlated with infiltrates of CD3+, CD4+, CD8+, and CD45+ immune cells. CTLA4 methylation did not correlate with protein expression in tumors, however, decitabine treatment led to decreased CTLA4 methylation and an induction of CTLA4 mRNA and CTLA-4 protein expression in HNSCC cell lines.

Conclusions
Our results indicate that CTLA4 DNA hypomethylation is a predictive biomarker for response to ICB in HNSCC. Our study warrants further analyses of the predictive value of CTLA4 DNA methylation in clinical trials of anti-PD-1 and/or anti-CTLA-4 immunotherapy in HNSCC.
MRI of endometriosis in correlation with the #Enzian classification: applicability and structured report
Authors: Maciel Cristina , Ferreira Hélder , Djokovic Dusan , Kyaw Tun Jimmy , Keckstein Jörg , Rizzo Stefania , Manganaro Lucia 
Published: July 2023

AbstractEndometriosis represents one of the most common causes of life-impacting chronic pelvic pain and female infertility. Magnetic resonance imaging (MRI) plays an increasing role in the diagnosis and mapping of endometriosis, while diagnostic laparoscopy currently tends to be reserved for the patients with negative imaging results. The #Enzian, published in 2021, proposes a new comprehensive classification system of endometriosis, combining a complete staging of deep infiltrative endometriosis with the evaluation of peritoneal/ovarian/tubal localizations and the presence of adenomyosis. This article addresses in detail the applicability of the #Enzian classification, primarily based on surgical findings, to the MRI evaluation of the endometriosis. Overall, there is a significant matching between MRI features and the #Enzian classification criteria, two different perspectives of endometriosis mapping, with different goals and levels of detail. The main discrepancy lies in the evaluation of tubo-ovarian condition, which is not fully assessable by MRI. Furthermore, as endometriosis is a complex disease, usually multifocal, that can present with a myriad of imaging findings, MRI reporting should be clear and well organized. The authors group, both radiologists and gynecologists, propose a structured MRI report of endometriosis in correlation with the #Enzian classification, merging the detailed anatomical and pre-operative information provided by the MRI with the benefits of a comprehensive classification system of endometriosis in the clinical practice and research field.Critical relevance statement This article addresses in detail the applicability of the #Enzian classification, primarily based on surgical findings, to the MRI evaluation of the endometriosis and proposes a #Enzian-based structured MRI report.
Graphical abstract
Self-healing of type B acute aortic dissection after aortic valve replacement: a case report
Authors: Jiang Ling , Xie Xiangrong , Wei Jun 
Published: July 2023

Abstract
Background
As a life-threatening and serious condition, aortic dissection (AD) is divided into type A and B according to its association with the ascending or descending aorta. Type A AD is often accompanied by aortic regurgitation, while type B dissections are rarely accompanied by severe aortic regurgitation.

Case presentation
We present a 71 year-old Chinese man with a rare case of type B AD with severe aortic insufficiency, who self-healed after 1 year of an aortic valve replacement. He complained of chest tightness and abdominal pain. Due to poor cardiac function, he underwent aortic valve replacement before intervening on the dissection. The operation was successful, and the dissection was treated conservatively. During the 1-year follow-up, his chest tightness improved, and the type B dissection was healed. His general condition is considerably improved.

Conclusions
In type B AD combined with severe aortic insufficiency, aortic valve replacement should be prioritized. This is potentially explained by the aortic root activity and pulse pressure difference.
Frequency of significant virulence genes in gastric biopsies of Helicobacter pylori-positive patients with gastritis
Authors: Gholamhosseinzadeh Ebrahim , Ghalehnoei Hossein , Kazemi Veisari Arash , Sheidaei Somayeh , Goli Hamid Reza 
Published: July 2023

AbstractHelicobacter pylori is one of the most common bacteria affecting human societies worldwide, and is mainly associated with gastrointestinal complications due to different virulence factors. This study aimed to investigate some virulence genes of H. pylori in gastric biopsies of patients with gastritis in Sari city, North of Iran. Informed consent forms were obtained from the studied patients, and those who needed endoscopy were included in the study. To evaluate the prevalence of cagA, iceA1, iceA2, vacA, dupA, and oipA genes, gastric biopsies with positive or negative rapid urease test were collected from 50 patients (25 in each group) with gastro-duodenal diseases. The bacterial DNAs were extracted by a specific kit, and the presence of the genes was analyzed by PCR using specific primers. Eighteen (72%) biopsies from 25 H. pylori-positive samples were cagA-positive, while 17 (68%) biopsies contained the vacA gene, and 11 (44%) samples had both vacA and cagA genes. However, 16 (64%), 12 (48%), 13 (52%), and 14 (56%) biopsies contained dupA, iceA1, iceA2, and oipA genes, respectively. Due to the significant role of the studied virulence factors in the pathogenicity of H. pylori, the high prevalence of these factors in biopsies of patients with gastritis is a concern needing to the management in this region.
High out‑of‑pocket spending and financial hardship at the end of life among cancer survivors and their families
Authors: Zhao Jingxuan , Yabroff K. Robin 
Published: July 2023

AbstractCancer is one of the most expensive medical conditions to treat worldwide, affecting national and local spending, as well as household budgets for patients and their families. In this commentary about a recent paper from Tur‑Sinai et al., we discuss the high out-of-pocket spending and medical and non-medical financial hardship faced by cancer patients and their families at the end-of-life in Israel. We provide recent information about the costs of health care in Israel and other high-income countries with (i.e., Canada, Australia, Japan, and Italy) and without universal health insurance coverage (i.e., United States, a country with high healthcare costs and uninsurance rate), and highlight the role of improving health insurance coverage and benefit design in reducing financial hardship among cancer patients and their families. Recognizing that financial hardship at the end of life affects both patients and their families, developing comprehensive programs and policies in Israel as well as in other countries is warranted.