bluuebunny/crossref_metadata_2025_split huggingface dataset:
A network medicine approach to study comorbidities in heart failure with preserved ejection fraction
Authors: Lanzer Jan D. , Valdeolivas Alberto , Pepin Mark , Hund Hauke , Backs Johannes , Frey Norbert , Friederich Hans-Christoph , Schultz Jobst-Hendrik , Saez-Rodriguez Julio , Levinson Rebecca T. 
Published: July 2023

Abstract
Background
Comorbidities are expected to impact the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). However, comorbidity profiles are usually reduced to a few comorbid disorders. Systems medicine approaches can model phenome-wide comorbidity profiles to improve our understanding of HFpEF and infer associated genetic profiles.

Methods
We retrospectively explored 569 comorbidities in 29,047 HF patients, including 8062 HFpEF and 6585 HF with reduced ejection fraction (HFrEF) patients from a German university hospital. We assessed differences in comorbidity profiles between HF subtypes via multiple correspondence analysis. Then, we used machine learning classifiers to identify distinctive comorbidity profiles of HFpEF and HFrEF patients. Moreover, we built a comorbidity network (HFnet) to identify the main disease clusters that summarized the phenome-wide comorbidity. Lastly, we predicted novel gene candidates for HFpEF by linking the HFnet to a multilayer gene network, integrating multiple databases. To corroborate HFpEF candidate genes, we collected transcriptomic data in a murine HFpEF model. We compared predicted genes with the murine disease signature as well as with the literature.

Results
We found a high degree of variance between the comorbidity profiles of HFpEF and HFrEF, while each was more similar to HFmrEF. The comorbidities present in HFpEF patients were more diverse than those in HFrEF and included neoplastic, osteologic and rheumatoid disorders. Disease communities in the HFnet captured important comorbidity concepts of HF patients which could be assigned to HF subtypes, age groups, and sex. Based on the HFpEF comorbidity profile, we predicted and recovered gene candidates, including genes involved in fibrosis (COL3A1, LOX, SMAD9, PTHL), hypertrophy (GATA5, MYH7), oxidative stress (NOS1, GSST1, XDH), and endoplasmic reticulum stress (ATF6). Finally, predicted genes were significantly overrepresented in the murine transcriptomic disease signature providing additional plausibility for their relevance.

Conclusions
We applied systems medicine concepts to analyze comorbidity profiles in a HF patient cohort. We were able to identify disease clusters that helped to characterize HF patients. We derived a distinct comorbidity profile for HFpEF, which was leveraged to suggest novel candidate genes via network propagation. The identification of distinctive comorbidity profiles and candidate genes from routine clinical data provides insights that may be leveraged to improve diagnosis and identify treatment targets for HFpEF patients.

Graphical Abstract
The expression profiles of signature genes from CD103+LAG3+ tumour-infiltrating lymphocyte subsets predict breast cancer survival
Authors: Xia Zi-An , Lu Can , Pan Can , Li Jia , Li Jun , Mao Yitao , Sun Lunquan , He Jiang 
Published: July 2023

Abstract
Background
Tumour-infiltrating lymphocytes (TILs), including T and B cells, have been demonstrated to be associated with tumour progression. However, the different subpopulations of TILs and their roles in breast cancer remain poorly understood. Large-scale analysis using multiomics data could uncover potential mechanisms and provide promising biomarkers for predicting immunotherapy response.

Methods
Single-cell transcriptome data for breast cancer samples were analysed to identify unique TIL subsets. Based on the expression profiles of marker genes in these subsets, a TIL-related prognostic model was developed by univariate and multivariate Cox analyses and LASSO regression for the TCGA training cohort containing 1089 breast cancer patients. Multiplex immunohistochemistry was used to confirm the presence of TIL subsets in breast cancer samples. The model was validated with a large-scale transcriptomic dataset for 3619 breast cancer patients, including the METABRIC cohort, six chemotherapy transcriptomic cohorts, and two immunotherapy transcriptomic cohorts.

Results
We identified two TIL subsets with high expression of CD103 and LAG3 (CD103+LAG3+), including a CD8+ T-cell subset and a B-cell subset. Based on the expression profiles of marker genes in these two subpopulations, we further developed a CD103+LAG3+ TIL-related prognostic model (CLTRP) based on CXCL13 and BIRC3 genes for predicting the prognosis of breast cancer patients. CLTRP-low patients had a better prognosis than CLTRP-high patients. The comprehensive results showed that a low CLTRP score was associated with a high TP53 mutation rate, high infiltration of CD8 T cells, helper T cells, and CD4 T cells, high sensitivity to chemotherapeutic drugs, and a good response to immunotherapy. In contrast, a high CLTRP score was correlated with a low TP53 mutation rate, high infiltration of M0 and M2 macrophages, low sensitivity to chemotherapeutic drugs, and a poor response to immunotherapy.

Conclusions
Our present study showed that the CLTRP score is a promising biomarker for distinguishing prognosis, drug sensitivity, molecular and immune characteristics, and immunotherapy outcomes in breast cancer patients. The CLTRP could serve as a valuable tool for clinical decision making regarding immunotherapy.
Adaptation of a community health outreach model during the COVID-19 pandemic: the case of the Mexican consulates in the United States of America
Authors: Gaitán-Rossi Pablo , Vilar-Compte Mireya , Bustamante Arturo Vargas 
Published: July 2023

AbstractThe Ventanillas de Salud (VDS – “Health Windows”) are a culturally sensitive outreach program within the 49 Mexican Consulates in the United States that provides information and health care navigation support to underserved and uninsured Mexican immigrants. During the COVID-19 pandemic the VDS rapidly transitioned to remote operations adding new services. Based on the EquIR implementation framework, this qualitative study investigates how adaptations to improve emergency preparedness were performed. We conducted motivational interviews with three actors – six VDS coordinators, eight partner organizations, and ten VDS users– in two VDS, Los Angeles and New York, to document specific needs of the target population and identify implementation processes to adapt and continue operating. The VDS adapted their model by adding new services for emerging needs, by switching service provision modalities, and by expanding the network of partner organizations. According to the VDS staff, these adaptations increased their topics, depth, reach, and diversified their users. Users had mostly positive opinions about the VDS adaptation, although they highlighted some heterogeneity across service provision. The VDS is a public health intervention able to serve a marginalized population and its implementation offers valuable lessons to complement health systems and to improve preparedness and resiliency for future crises.
Recent advance in bioactive hydrogels for repairing spinal cord injury: material design, biofunctional regulation, and applications
Authors: Sun Zhengang , Zhu Danzhu , Zhao Hong , Liu Jia , He Peng , Luan Xin , Hu Huiqiang , Zhang Xuanfen , Wei Gang , Xi Yongming 
Published: July 2023

AbstractFunctional hydrogels show potential application in repairing spinal cord injury (SCI) due to their unique chemical, physical, and biological properties and functions. In this comprehensive review, we present recent advance in the material design, functional regulation, and SCI repair applications of bioactive hydrogels. Different from previously released reviews on hydrogels and three-dimensional scaffolds for the SCI repair, this work focuses on the strategies for material design and biologically functional regulation of hydrogels, specifically aiming to show how these significant efforts can promoting the repairing performance of SCI. We demonstrate various methods and techniques for the fabrication of bioactive hydrogels with the biological components such as DNA, proteins, peptides, biomass polysaccharides, and biopolymers to obtain unique biological properties of hydrogels, including the cell biocompatibility, self-healing, anti-bacterial activity, injectability, bio-adhesion, bio-degradation, and other multi-functions for repairing SCI. The functional regulation of bioactive hydrogels with drugs/growth factors, polymers, nanoparticles, one-dimensional materials, and two-dimensional materials for highly effective treating SCI are introduced and discussed in detail. This work shows new viewpoints and ideas on the design and synthesis of bioactive hydrogels with the state-of-the-art knowledges of materials science and nanotechnology, and will bridge the connection of materials science and biomedicine, and further inspire clinical potential of bioactive hydrogels in biomedical fields.
Cost-effectiveness analysis of ceftazidime avibactam versus colistin in carbapenem-resistant enterobacteriaceae in Iran
Authors: Goudarzi Zahra , Danayi Fattaneh , Keshavarz Khosro , Gholami Ahmad 
Published: July 2023

Abstract
Introduction
Ceftazidime avibactam (CA) is an effective treatment against carbapenem-resistant Enterobacteriaceae (CRE), but its cost-effectiveness is unclear. This study was performed to evaluate the cost-effectiveness of CA against the best available treatment colistin (Col) for patients with CRE-related infections in Iran.

Methodology
A model of a decision tree was designed to evaluate the cost-effectiveness of CA in CRE patients over a period of 5 years. The Iran health system was the perspective of the study, and the discount rates of 5.8% and 3% were considered for the data of cost and utility, respectively. The clinical inputs were obtained from a prospective observational study. We established the costs of medical services and medical tariffs of Iran’s health system, and obtained the rate of medical service resources used by patients from specialists. The results of this model included the quality-adjusted life years (QALYs), increasing costs, and incremental cost-utility ratio (ICUR). We also performed the deterministic and probabilistic sensitivity analyses.

Results
CA reduced the burden of related to treatment failure and the need for treatment of nephrotoxicity and chronic failure, whereas, the costs related to drug procurement and long-term care (due to longer survival) increased. Treatment with CA versus Col resulted in a 53% increase in QALYs and $425 in costs, leading to an ICUR equal to 798 $/QALYs. Sensitivity analyses proved the model’s strength and indicated that the cost-effectiveness of CA can reach 88% when paying 1111 $/QALY. Budget impact analysis estimated CA regimen will increase the health system costs by $1,270,462 in 5 years.

Conclusion
In Iranian settings, CA can significantly increase the quality of life and patients’ survival; therefore, in comparison to the Col drug regimen, CA is a cost-effective strategy.
Insulin alleviates murine colitis through microbiome alterations and bile acid metabolism
Authors: He Shuying , Li Jiating , Yao Zirong , Gao Zixian , Jiang Yonghong , Chen Xueqing , Peng Liang 
Published: July 2023

Abstract
Background
Insulin has been reported to exhibit anti-inflammatory activities in the context of bowel inflammation. However, the role of the interaction between insulin and the microbiota in gut health is unclear. Our goal was to investigate the mechanism of action of insulin in bowel inflammation and the relationship between insulin and the gut microbiota.

Methods
We used acute and chronic murine models of inflammatory bowel disease (IBD) to evaluate whether insulin influences the progression of colitis. Colonic tissues, the host metabolome and the gut microbiome were analyzed to investigate the relationship among insulin treatment, the microbiome, and disease. Experiments involving antibiotic (Abx) treatment and fecal microbiota transplantation (FMT) confirmed the association among the gut microbiota, insulin and IBD. In a series of experiments, we further defined the mechanisms underlying the anti-inflammatory effects of insulin.

Results
We found that low-dose insulin treatment alleviated intestinal inflammation but did not cause death. These effects were dependent on the gut microbiota, as confirmed by experiments involving Abx treatment and FMT. Using untargeted metabolomic profiling and 16S rRNA sequencing, we discovered that the level of the secondary bile acid lithocholic acid (LCA) was notably increased and the LCA levels were significantly associated with the abundance of Blautia, Enterorhadus and Rumi-NK4A214_group. Furthermore, LCA exerted anti-inflammatory effects by activating a G-protein-coupled bile acid receptor (TGR5), which inhibited the polarization of classically activated (M1) macrophages.

Conclusion
Together, these data suggest that insulin alters the gut microbiota and affects LCA production, ultimately delaying the progression of IBD.

Graphical Abstract
Effects of meteorological conditions on brood care in cooperatively breeding carrion crow and consequences on reproductive success
Authors: Trapote Eva , Canestrari Daniela , Baglione Vittorio 
Published: July 2023

AbstractMeteorological stressors (e.g., temperature and rain shortage) constrain brood provisioning in some bird species, but the consequences on reproductive success have been rarely quantified. Here we show, in a cooperatively breeding population of carrion crowCorvus coronein Spain, that individual feeding rates decreased significantly with rising air temperatures both in breeders and helpers, while lack of rain was associated with a significant reduction in the effort of the male helpers as compared to the other social categories. Group coordination, measured as the degree of alternation of nest visits by carers, was also negatively affected by rising temperature. Furthermore, we found that the body condition of the nestlings worsened when temperatures were high during the rearing period. Interestingly, the analysis of a long-term data set on crow reproduction showed that nestling body condition steadily deteriorated over the last 26-years. Although many factors may concur in causing population changes, our data suggest a possible causal link between global warming, brood caring behaviour and the decline of carrion crow population in the Mediterranean climatic region of Spain.
Evaluating the usability of a co-designed power assisted exercise graphical user interface for people with stroke
Authors: Young Rachel , Sage Karen , Broom David , Hext Andrew , Snowdon Nicky , Smith Christine 
Published: July 2023

Abstract
Background
Digital advancement of power assisted exercise equipment will advance exercise prescription for people with stroke (PwS). This article reports on the remote usability evaluation of a co-designed graphical user interface (GUI) and denotes an example of how video-conference software can increase reach to participants in the testing of rehabilitation technologies. The aim of this study was to evaluate the usability of two sequential versions of the GUI.

Methods
We adopted a mixed methods approach. Ten professional user (PU) (2M/8F) and 10 expert user (EU) participants (2M/8F) were recruited. Data collection included a usability observation, a ‘think aloud’ walk through, task completion, task duration and user satisfaction as indicated by the Post Study System Usability Questionnaire (PSSUQ). Identification of usability issues informed the design of version 2 which included an additional submenu. Descriptive analysis was conducted upon usability issues and number of occurrences detected on both versions of the GUI. Inferential analysis enabled comparison of task duration and PSSUQ data between the PU and EU groups.

Results
Analysis of the ‘think aloud’ walkthrough data enabled identification of 22 usability issues on version 1 from a total of 100 usability occurrences. Task completion for all tasks was 100%. Eight usability issues were directly addressed in the development of version 2. Two recurrent and 24 new usability issues were detected in version 2 with a total of 86 usability occurrences. Paired two tailed T-tests on task duration data indicated a significant decrease amongst the EU group for task 1.1 on version 2 (P = 0.03). The mean PSSUQ scores for version 1 was 1.44 (EU group) and 1.63 (PU group) compared with 1.40 (EU group) and 1.41 (PU group) for version 2.

Conclusions
The usability evaluation enabled identification of usability issues on version 1 of the GUI which were effectively addressed on the iteration of version 2. Testing of version 2 identified usability issues within the new submenu. Application of multiple usability evaluation methods was effective in identifying and addressing usability issues in the GUI to improve the experience of PAE for PwS. The use of video-conference software to conduct synchronous, remote usability testing is an effective alternative to face to face testing methods.
Posterior unilateral small fenestration of lamina combined with a custom-made Y-shaped fracture reduction device for the treatment of severe thoracolumbar burst fracture: a prospective comparative study
Authors: Zeng Zheng , Zhang Dan , Zeng Fen-Lian , Ao Jun 
Published: July 2023

Abstract
Background
The purpose was to evaluate the clinical effect of a custom-made Y-shaped fracture fragment reduction device and to assist in posterior unilateral small fenestration of lamina to reduce the fracture fragments.

Methods
In this study, 40 patients were assigned to one of two groups: the traditional reduction device group (TRG) or the Y-shaped reduction device group (YRG). All patients underwent posterior unilateral small fenestration of the lamina and direct decompression through the spinal canal. And the operation time (OT), intraoperative bleeding (IB), preoperative, postoperative, and final follow-up data on the spinal stenosis rate (SSR), Cobb angle, the anterior compression ratio of injured vertebrae (ACRIV), and ASIA neurological function grade were compared between the two groups.

Result
There were no complications, including vascular and nerve injury, serious postoperative infection, internal fixation fracture, or loosening, for any of the patients. And the average follow-up time of the two groups was 14.2 months, the average operation time of the TRG was 236.6 min, and the average intraoperative blood loss was 357.20 ml. Moreover, the average operation time of the YRG was 190.6 min, and the average intraoperative blood loss was 241.5 ml. There were significant differences between the two groups in terms of operation duration and intraoperative blood loss. The YRG's was lower than that of the TRG. Besides, there was no difference in SSR, Cobb angle, ACRIV, or neurological recovery between the two groups before or immediately after the operation or at the last follow-up.

Conclusion
The Y-shaped fracture reduction device can reduce the fracture fragments and the OT and IB stably; it also has satisfactory postoperative curative effects and clinical utility.
Preoperative small pulmonary nodule localisation using hookwires or coils: strategy selection in adverse events
Authors: Zuo Tao , Gao Zhaoming , Zhang Tao , Wen Bing , Chen Baojun , Jiang Ping 
Published: July 2023

Abstract
Objective
This is a retrospective study of adverse events associated with preoperative computed tomography (CT)–guided hookwire or coil localisation. We analysed the experience and process flaws in resecting ground-glass nodules (GGNs) through video-assisted thoracoscopic surgery (VATS) and determined the remedial strategy.

Methods
Adverse events were evaluated in 40 patients with 45 GGNs who underwent CT-guided hookwire or coil localisation before VATS. For lesions not successfully marked or detected, palpation, resection of the highly suspected area, segmentectomy or lobectomy was performed.

Results
Among all adverse events, 15 were dislodgement of the marking materials, 5 were breakaway of the marking materials, 7 were > 2 cm distance between the lesions and the tips, 3 was marking material across the two adjacent lobes, 15 were pneumothorax and 2 were certain parts of marking materials stuck into the chest wall. All GGNs were resected successfully. 20 lesions were detected by palpation. 9 GGNs were discovered after the resection of highly suspected areas. Segmentectomies and lobectomies were performed directly on 7 and 9 GGNs, respectively.

Conclusions
When adverse events occur, a second intraoperative localisation, by resecting the highly suspected area either through non-anatomical resection (wedge resection) or anatomical resection (segmentectomy or lobectomy) using the VATS should be considered the alternatives for GGNs localization.
Uncovering the mechanisms of Yi Qi Tong Qiao Pill in the treatment of allergic rhinitis based on Network target analysis
Authors: Wang Boyang , Zhang Dingfan , Zhang Tingyu , Sutcharitchan Chayanis , Hua Jianlin , Hua Dongfang , Zhang Bo , Li Shao 
Published: July 2023

Abstract
Objective
The purpose of this study is to reveal the mechanism of action of Yi Qi Tong Qiao Pill (YQTQP) in the treatment of allergic rhinitis (AR), as well as establish a paradigm for the researches on traditional Chinese medicine (TCM) from systematic perspective.

Methods
Based on the data collected from TCM-related and disease-related databases, target profiles of compounds in YQTQP were calculated through network-based algorithms and holistic targets of TQTQP was constructed. Network target analysis was performed to explore the potential mechanisms of YQTQP in the treatment of AR and the mechanisms were classified into different modules according to their biological functions. Besides, animal and clinical experiments were conducted to validate our findings inferred from Network target analysis.

Results
Network target analysis showed that YQTQP targeted 12 main pathways or biological processes related to AR, represented by those related to IL-4, IFN-γ, TNF-α and IL-13. These results could be classified into 3 biological modules, including regulation of immune and inflammation, epithelial barrier disorder and cell adhesion. Finally, a series of experiments composed of animal and clinical experiments, proved our findings and confirmed that YQTQP could improve related symptoms of AR, like permeability of nasal mucosa epithelium.

Conclusion
A combination of Network target analysis and the experimental validation indicated that YQTQP was effective in the treatment of AR and might provide a new insight on revealing the mechanism of TCM against diseases.
Trial registration Name of the registry: Chinese Clinical Trial Registry: Trial registration number: ChiCTR-TRC-13,003,137: Date of registration: Registered 29 March 2013 - Retrospectively registered: URL of trial registry record: https://www.chictr.org.cn/showproj.html?proj=6422.