bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tongbi Huoluo Decoction alleviates cartilage degeneration in knee osteoarthritis by inhibiting degradation of extracellular matrix
Authors: Chen Weijian , Liu Weinian , Jiang Tao , Liu Lingyun , He Qi , Lin Tianye , Zhang Jiayuan , Huo Liwei , Xu Xuemeng , Wang Haibin , Liang Du , Liu Wengang 
Published: July 2023

Abstract
Background
Knee osteoarthritis (KOA) is an age-related degenerative disease characterized by abrasion of articular cartilage. Tongbi Huoluo Decoction (TBHLD) has been transformed from the famous traditional Chinese medicine Duhuo Jisheng Decoction, which can effectively alleviate pain symptoms in KOA. However, the active components and mechanisms of TBHLD in treating KOA have not yet been elucidated. The purpose of the study was to demonstrate the molecular mechanism of TBHLD in treating KOA.

Methods
The components and targets of TBHLD and KOA were collected from multiple databases, and the protein to protein interaction (PPI) network was constructed. Next, we performed topological calculation and enrichment analysis. Besides, we performed virtual screening for molecular docking and molecular dynamics simulation (MDS). Furthermore, the vitro and vivo experiments were performed to evaluate the validity and mechanism of TBHLD.

Results
206 active components and 187 potential targets were screened from Tongbi Huoluo Decoction. A total of 50 intersecting genes were identified between TBHLD and KOA, 20 core targets were calculated by network topology analysis. The core targets were enriched in the ECM interaction pathways. The results of virtual screening for molecular docking and MDS showed that the active components of TBHLD had steady binding conformations with core genes. Moreover, we identified 32 differential serum components in TBHLD-containing serum using LC–MS, including 22 upregulated and 10 downregulated serum components. TBHLD improved the proliferation activity of OA chondrocytes, decreased the expression of Col1a1, Col1a2, Mmp2, Mmp13 in OA chondrocytes, ameliorated the cartilage lesions and restored the cartilage abrasion.

Conclusion
TBHLD inhibited degradation of cartilage ECM by regulating the expression of type I collagens and Mmps to ameliorate cartilage degeneration in KOA.
Super-enhancers complexes zoom in transcription in cancer
Authors: Wang MengTing , Chen QingYang , Wang ShuJie , Xie Han , Liu Jun , Huang RuiXiang , Xiang YuFei , Jiang YanYi , Tian DaSheng , Bian ErBao 
Published: July 2023

AbstractSuper-enhancers (SEs) consist of multiple typical enhancers enriched at high density with transcription factors, histone-modifying enzymes and cofactors. Oncogenic SEs promote tumorigenesis and malignancy by altering protein-coding gene expression and noncoding regulatory element function. Therefore, they play central roles in the treatment of cancer. Here, we review the structural characteristics, organization, identification, and functions of SEs and the underlying molecular mechanism by which SEs drive oncogenic transcription in tumor cells. We then summarize abnormal SE complexes, SE-driven coding genes, and noncoding RNAs involved in tumor development. In summary, we believe that SEs show great potential as biomarkers and therapeutic targets.
Fructose promotes angiogenesis by improving vascular endothelial cell function and upregulating VEGF expression in cancer cells
Authors: Cui Yanfen , Liu Hui , Wang Zhaosong , Zhang He , Tian Jianfei , Wang Zhiyong , Song Weijie , Guo Hui , Liu Liming , Tian Ruinan , Zuo Xiaoyan , Ren Sixin , Zhang Fei , Niu Ruifang 
Published: July 2023

Abstract
Background
Fructose is a very common sugar found in natural foods, while current studies demonstrate that high fructose intake is significantly associated with increased risk of multiple cancers and more aggressive tumor behavior, but the relevant mechanisms are not fully understood.

Methods
Tumor-grafting experiments and in vitro angiogenesis assays were conducted to detect the effect of fructose and the conditioned medium of fructose-cultured tumor cells on biological function of vascular endothelial cells (VECs) and angiogenesis. 448 colorectal cancer specimens were utilized to analyze the relationship between Glut5 expression levels in VECs and tumor cells and microvascular density (MVD).

Results
We found that fructose can be metabolized by VECs and activate the Akt and Src signaling pathways, thereby enhancing the proliferation, migration, and tube-forming abilities of VECs and thereby promoting angiogenesis. Moreover, fructose can also improve the expression of vascular endothelial growth factor (VEGF) by upregulating the production of reactive oxygen species (ROS) in colorectal cancer cells, thus indirectly enhancing the biological function of VECs. Furthermore, this pro-angiogenic effect of fructose metabolism has also been well validated in clinical colorectal cancer tissues and mouse models. Fructose contributes to angiogenesis in mouse subcutaneous tumor grafts, and MVD is positively correlated with Glut5 expression levels of both endothelial cells and tumor cells of human colorectal cancer specimens.

Conclusions
These findings establish the direct role and mechanism by which fructose promotes tumor progression through increased angiogenesis, and provide reliable evidence for a better understanding of tumor metabolic reprogramming.
Simultaneous venous–arterial Doppler during preload augmentation: illustrating the Doppler Starling curve
Authors: Kenny Jon-Émile S. , Gibbs Stanley O. , Eibl Joseph K. , Eibl Andrew M. , Yang Zhen , Johnston Delaney , Munding Chelsea E. , Elfarnawany Mai , Lau Vivian C. , Kemp Benjamin O. , Nalla Bhanu , Atoui Rony 
Published: July 2023

AbstractProviding intravenous (IV) fluids to a patient with signs or symptoms of hypoperfusion is common. However, evaluating the IV fluid ‘dose–response’ curve of the heart is elusive. Two patients were studied in the emergency department with a wireless, wearable Doppler ultrasound system. Change in the common carotid arterial and internal jugular Doppler spectrograms were simultaneously obtained as surrogates of left ventricular stroke volume (SV) and central venous pressure (CVP), respectively. Both patients initially had low CVP jugular venous Doppler spectrograms. With preload augmentation, only one patient had arterial Doppler measures indicative of significant SV augmentation (i.e., ‘fluid responsive’). The other patient manifested diminishing arterial response, suggesting depressed SV (i.e., ‘fluid unresponsive’) with evidence of ventricular asynchrony. In this short communication, we describe how a wireless, wearable Doppler ultrasound simultaneously tracks surrogates of cardiac preload and output within a ‘Doppler Starling curve’ framework; implications for IV fluid dosing are discussed.
Personalized estimates of brain cortical structural variability in individuals with Autism spectrum disorder: the predictor of brain age and neurobiology relevance
Authors: Xie Yingying , Sun Jie , Man Weiqi , Zhang Zhang , Zhang Ningnannan 
Published: July 2023

Abstract
Background
Autism spectrum disorder (ASD) is a heritable condition related to brain development that affects a person’s perception and socialization with others. Here, we examined variability in the brain morphology in ASD children and adolescent individuals at the level of brain cortical structural profiles and the level of each brain regional measure.

Methods
We selected brain structural MRI data in 600 ASDs and 729 normal controls (NCs) from Autism Brain Imaging Data Exchange (ABIDE). The personalized estimate of similarity between gray matter volume (GMV) profiles of an individual to that of others in the same group was assessed by using the person-based similarity index (PBSI). Regional contributions to PBSI score were utilized for brain age gap estimation (BrainAGE) prediction model establishment, including support vector regression (SVR), relevance vector regression (RVR), and Gaussian process regression (GPR). The association between BrainAGE prediction in ASD and clinical performance was investigated. We further explored the related inter‐regional profiles of gene expression from the Allen Human Brain Atlas with variability differences in the brain morphology between groups.

Results
The PBSI score of GMV was negatively related to age regardless of the sample group, and the PBSI score was significantly lower in ASDs than in NCs. The regional contributions to the PBSI score of 126 brain regions in ASDs showed significant differences compared to NCs. RVR model achieved the best performance for predicting brain age. Higher inter-individual brain morphology variability was related to increased brain age, specific to communication symptoms. A total of 430 genes belonging to various pathways were identified as associated with brain cortical morphometric variation. The pathways, including short-term memory, regulation of system process, and regulation of nervous system process, were dominated mainly by gene sets for manno midbrain neurotypes.

Limitations
There is a sample mismatch between the gene expression data and brain imaging data from ABIDE. A larger sample size can contribute to the model training of BrainAGE and the validation of the results.

Conclusions
ASD has personalized heterogeneity brain morphology. The brain age gap estimation and transcription-neuroimaging associations derived from this trait are replenished in an additional direction to boost the understanding of the ASD brain.
Difficult diagnosis in the clinical evaluation of a patient with squamous cell carcinoma of the sigmoid colon: a case report
Authors: Garro-Mendiola Alonso , Guevara-Lazo David , Samanez Willian Pinto , Lizarzaburu-Robles Juan Carlos 
Published: July 2023

Abstract
Background
Squamous cell carcinoma (SCC) of the sigmoid colon is an exceedingly rare subtype of colorectal cancer (CRC) associated with chronic inflammatory conditions. Due to its variable clinical presentation ranging from subclinical to fully symptomatic and limited available information, it poses a diagnostic challenge. We aim to provide a review of the current literature and raise awareness about the importance of a thorough clinical analysis for an early diagnosis.

Case presentation
We describe the case of a 59-year-old Peruvian woman with a medical history of diverticular disease and irritable bowel syndrome. The patient presented with nonspecific symptoms such as abdominal discomfort, constipation, and bloating. Diagnostic tests and biopsy revealed a rare case of squamous cell carcinoma of the sigmoid colon. The patient underwent surgical resection and adjuvant chemotherapy.

Conclusion
Despite the rarity of this type of cancer in the colon, the patient's clinical course highlights the importance of considering it as a potential diagnosis in patients with nonspecific symptoms and a history of gastrointestinal disorders. Surgical treatment followed by radiotherapy is the preferred management. Factors such as lack of postoperative complications and the stage of the neoplasia can augur a positive. prognosis. A prompt diagnosis is crucial, as detecting a neoplasia in its early stages can make surgery more effective.
hESC-derived striatal progenitors grafted into a Huntington’s disease rat model support long-term functional motor recovery by differentiating, self-organizing and connecting into the lesioned striatum
Authors: Schellino Roberta , Besusso Dario , Parolisi Roberta , Gómez-González Gabriela B. , Dallere Sveva , Scaramuzza Linda , Ribodino Marta , Campus Ilaria , Conforti Paola , Parmar Malin , Boido Marina , Cattaneo Elena , Buffo Annalisa 
Published: July 2023

Abstract
Background
Huntington’s disease (HD) is a motor and cognitive neurodegenerative disorder due to prominent loss of striatal medium spiny neurons (MSNs). Cell replacement using human embryonic stem cells (hESCs) derivatives may offer new therapeutic opportunities to replace degenerated neurons and repair damaged circuits.

Methods
With the aim to develop effective cell replacement for HD, we assessed the long-term therapeutic value of hESC-derived striatal progenitors by grafting the cells into the striatum of a preclinical model of HD [i.e., adult immunodeficient rats in which the striatum was lesioned by monolateral injection of quinolinic acid (QA)]. We examined the survival, maturation, self-organization and integration of the graft as well as its impact on lesion-dependent motor alterations up to 6 months post-graft. Moreover, we tested whether exposing a cohort of QA-lesioned animals to environmental enrichment (EE) could improve graft integration and function.

Results
Human striatal progenitors survived up to 6 months after transplantation and showed morphological and neurochemical features typical of human MSNs. Donor-derived interneurons were also detected. Grafts wired in both local and long-range striatal circuits, formed domains suggestive of distinct ganglionic eminence territories and displayed emerging striosome features. Moreover, over time grafts improved complex motor performances affected by QA. EE selectively increased cell differentiation into MSN phenotype and promoted host-to-graft connectivity. However, when combined to the graft, the EE paradigm used in this study was insufficient to produce an additive effect on task execution.

Conclusions
The data support the long-term therapeutic potential of ESC-derived human striatal progenitor grafts for the replacement of degenerated striatal neurons in HD and suggest that EE can effectively accelerate the maturation and promote the integration of human striatal cells.
Vertical nanoscale strain-induced electronic localization in epitaxial La2/3Sr1/3MnO3 films with ZrO2 nanopillar inclusions
Authors: Gao Yuze , Roldan Manuel A. , Qiao Liang , Mandrus David , Shen Xuechu , Chisholm Matthew F. , Singh David J. , Cao Guixin 
Published: July 2023

AbstractUnusual electrical transport properties associated with weak or strong localization are sometimes found in disordered electronic materials. Here, we report experimental observation of a crossover of electronic behavior from weak localization to enhanced weak localization due to the spatial influence of disorder induced by ZrO2 nanopillars in (La2/3Sr1/3MnO3)1−x:(ZrO2)x (x = 0, 0.2, and 0.3) nanocomposite films. The spatial strain regions, identified by scanning transmission electron microscopy and high-resolution x-ray diffraction, induce a coexistence of two-dimentional (2D) and three-dimentional (3D) localization and switches to typical 2D localization with increasing density of ZrO2 pillars due to length scale confinement, which interestingly accords with enhancing vertically interfacial strain. Based on the excellent agreement of our experimental results with one-parameter scaling theory of localization, the enhanced weak localization exists in metal range close to the fixed point. These films provide a tunable experimental model for studying localization in particular the transition regime by appropriate choice of the second epitaxial phase.
Graphical Abstract
“It’s research, our input can grow”: identifying health research priorities with Aboriginal and Torres Strait Islander communities—study protocol
Authors: Massi Luciana , Weatherall Loretta , Nielsen Christine , Toombs Maree , Fredericks Bronwyn , Rae Kym M. 
Published: July 2023

Abstract
Background
In Australia, Aboriginal and Torres Strait Islander (Indigenous) families have strong, cohesive, and nurturing cultural practices that contribute to effective family functioning and child rearing. These practices can lead to positive effects on children and communities, and include kinship relations, traditional knowledge systems, collective community focus, respect for Elders contributions, and spirituality. However, poor health and wellbeing outcomes exist across the lifespan for Indigenous Australians. Health programs, services and research that support Indigenous women, babies and their families are a critical investment to improve birthing and health outcomes and impact the life trajectories of Indigenous Australians.

Aim
The Indigenous Health Research Priorities study aims to identify the research priorities for families during the perinatal and early childhood period through a co-designed and collaborative process. This has been led by communities to determine the priorities identified with and for local Indigenous families in Queensland. This paper aims to report on engagement and involvement with Indigenous communities to identity health research priorities for families and presents preliminary findings of the research process including participants’ demographic information and feedback on the yarning sessions, as part of the study protocol.

Methods
The study protocol showcases the Participatory Action Research approach, yarning sessions with clients and staff of three community-controlled health services to date, and Delphi workshop methods to prioritise the health issues identified during the yarns with corresponding communities. The study will undertake qualitative data collection and analysis to identify and report on community and health service research priorities for Indigenous families in Queensland. A short survey was conducted to collect participants’ demographic information. A feedback form with five open-ended questions was also administered to collect data on participants’ views and satisfaction with the research process.

Preliminary results
This protocol paper reports on the participant demographic information and feedback on the research process and reactions to participating in the yarning sessions. There have been 12 yarning sessions in Far North Queensland to date. The qualitative analysis of these will be reported on in future, with South East Queensland and further sites to follow. Feedback from 61 community members and health professionals has highlighted they valued sharing stories, being heard, and feeling hopeful. Preliminary findings will be reported.

Discussion
Identification of health research priorities will allow each organisation and region of Queensland to develop research initiatives and the translational outcomes that are a focus for their community members.
Emergency team competencies: scoping review for the development of a tool to support the briefing and debriefing activities of emergency healthcare providers
Authors: Lorenzini Gabriele , Zamboni Alberto , Gelati Luca , Di Martino Alberto , Pellacani Alberto , Barbieri Nicolò , Baraldi Marcello 
Published: July 2023

AbstractGlobally, at least one adverse event occurs in 10% of patients using emergency, inpatient, outpatient, surgical and primary care services. Particularly in emergency health care, this problem is exacerbated by additional variables such as patient criticality, high-risk diagnostic and therapeutic interventions and varying levels of healthcare provider training. In relation to the last point, briefing and debriefing activities during an emergency reinforce staff training and support them in managing work resources, planning interventions and improving future performance. The aim of the scoping review is to explore the state of the art in human factors applied to emergency situations and to develop a new tool to support healthcare professionals in conducting evidence-based briefings and debriefings. This review was developed using a search strategy based on the Arksey and O’Malley’s six-step framework for scoping reviews. The literature analysed and the data identified, which are heterogeneous due to different study methodologies, objectives and types of interventions, suggest that human factors applied to emergency situations are still under-researched. At the end of the data extraction, analysis process, authors’ reviews, discussion rounds and comparison with the multidisciplinary team of healthcare providers, 42 behaviours, 33 elements and 8 domains were considered relevant and included in the Emergency Team Comptencies (ETC) briefing and debriefing tool, ranked in order of priority as follows: communication, decision-making, clinical skills, situational awareness, leadership, task management, collaboration and stress and fatigue management. Further research is needed to investigate human factors applied to emergency situations and to generate new evidence to improve clinical practice and reduce the risk of error. In the near future, further studies will be conducted by the authors to test the validity of the Emergency Team Competencies tool in objectively measuring the performance of professionals and multidisciplinary teams.
Contribution of MEK Inhibition to BRAF/MEK Inhibitor Combination Treatment of BRAF-Mutant Melanoma: Part 2 of the Randomized, Open-Label, Phase III COLUMBUS Trial
Authors: Ascierto Paolo A. , Dummer Reinhard , Gogas Helen J. , Arance Ana , Mandala Mario , Liszkay Gabriella , Garbe Claus , Schadendorf Dirk , Krajsova Ivana , Gutzmer Ralf , Chiarion-Sileni Vanna , Dutriaux Caroline , de Groot Jan Willem B. , Yamazaki Naoya , Loquai Carmen , Robert Caroline , Flaherty Keith T. 
Published: July 2023

PURPOSE In COLUMBUS part 1, patients with advanced BRAFV600-mutant melanoma were randomly assigned 1:1:1 to encorafenib 450 mg once daily plus binimetinib 45 mg twice a day (COMBO450), vemurafenib 960 mg twice a day, or encorafenib 300 mg once daily (ENCO300). As previously reported, COMBO450 improved progression-free survival (PFS) versus vemurafenib (part 1 primary end point) and ENCO300 (part 1 key secondary end point; not statistically significant). Part 2, requested by the US Food and Drug Administration, evaluated the contribution of binimetinib by maintaining the same encorafenib dosage in the combination (encorafenib 300 mg once daily plus binimetinib 45 mg twice daily [COMBO300]) and ENCO300 arms. METHODS In part 2, patients were randomly assigned 3:1 to COMBO300 or ENCO300. ENCO300 (parts 1 and 2) data were combined, per protocol, for PFS analysis (key secondary end point) by a blinded independent review committee (BIRC). Other analyses included overall response rate (ORR), overall survival, and safety. RESULTS Two hundred fifty-eight patients received COMBO300, and 86 received ENCO300. Per protocol, ENCO300 arms (parts 1 and 2 combined) were also evaluated (n = 280). The median follow-up for ENCO300 was 40.8 months (part 1) and 57.1 months (part 2). The median PFS (95% CI) was 12.9 months (10.9 to 14.9) for COMBO300 versus 9.2  months (7.4 to 11.1) for ENCO300 (parts 1  and  2) and 7.4  months (5.6 to 9.2) for ENCO300 (part 2). The hazard ratio (95% CI) for COMBO300 was 0.74 (0.60 to 0.92; two-sided P = .003) versus ENCO300 (parts 1  and  2). The ORR by BIRC (95% CI) was 68% (62 to 74) and 51% (45 to 57) for COMBO300 and ENCO300 (parts 1  and  2), respectively. COMBO300 had greater relative dose intensity and fewer grade 3/4 adverse events than ENCO300. CONCLUSION COMBO300 improved PFS, ORR, and tolerability compared with ENCO300, confirming the contribution of binimetinib to efficacy and safety.