bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silico analysis of prognostic and diagnostic significance of target genes from prostate cancer cell lines derived exomicroRNAs
Authors: Altuna-Coy Antonio , Ruiz-Plazas Xavier , Arreaza-Gil Verónica , Segarra-Tomás José , Chacón Matilde R. 
Published: November 2023

Abstract
Background
Cancer-secreted exovesicles are important for cell-to-cell communication by altering cancer-related signalling pathways. Exovesicles-derived miRNAs (exomiRNAs)-target genes can be useful for diagnostic and prognostic purposes.

Methods
ExomiRNA from prostate cancer (PCa) cells (PC-3 and LNCaP) were quantified by qRT-PCR and compared to the healthy cell line RWPE-1 by using miRNome PCR 752 miRNAs Panel. MiRNet database was used to predict exomiRNA-target genes. ExomiRNA-target genes pathway functional enrichment was performed by using Reactome database and Enrichr platform. Protein–protein interaction analysis was carried out by using the STRING database. RNA target-gene sequencing data from The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) database was screened out in 465 PCa patients for candidate gene expression in prostate tumour (PT) tissue and non-pathologic prostate (N-PP) tissue. Signature gene candidates were statistically analysed for diagnosis and prognosis usefulness.

Results
A total of 36 exomiRNAs were found downregulated when comparing PCa cells vs a healthy cell line; and when comparing PC-3 vs LNCaP, 14 miRNAs were found downregulated and 52 upregulated. Reactome pathway database revealed altered pathways and genes related to miRNA biosynthesis, miRNA-mediated gene silencing (TNRC6B and AGO1), and cell proliferation (CDK6), among others. Results showed that TNRC6B gene expression was up-regulated in PT tissue compared to N-PP (n = 52 paired samples) and could be useful for diagnostic purposes. Likewise, gene expression levels of CDK6, TNRC6B, and AGO1 were down-regulated in high-risk PT (n = 293) compared to low-risk PCa tissue counterparts (n = 172). When gene expression levels of CDK6, TNRC6B, and AGO1 were tested as a prognostic panel, the results showed that these improve the prognostic power of classical biomarkers.

Conclusion
ExomiRNAs-targets genes, TNRC6B, CDK6, and AGO1, showed a deregulated expression profile in PCa tissue and could be useful for PCa diagnosis and prognosis.
Higher intakes of fiber, total vegetables, and fruits may attenuate the risk of all-cause and cause-specific mortality: findings from a large prospective cohort study
Authors: Ghorbani Zeinab , Noormohammadi Morvarid , Kazemi Asma , Poustchi Hossein , Pourshams Akram , Martami Fahimeh , Hashemian Maryam , Malekzadeh Reza , Hekmatdoost Azita 
Published: November 2023

Abstract
Background
Although studies have reported an inverse association between fruits, vegetables, and fiber consumption and all-cause and cause-specific mortality, the issue remains incompletely defined in the Middle Eastern population.

Aims
The current study aimed to investigate the association between dietary fiber, fruit, and vegetable intake and all-cause and cause-specific mortality.

Methods
A total of 48632 participants (mean age = 52years), 57.5% (n = 27974) women and 42.5% (n = 20658) men, were recruited from an ongoing large-scale prospective cohort study (the Golestan Cohort Study (GCS)), in the north of Iran. Using a validated semi-quantitative 116-item food questionnaire, dietary intakes were collected. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) of all-cause and cause-specific mortality were reported.

Results
After approximately 14 years of follow-up, 10,774 deaths were recorded. In the fully adjusted model, compared to those in the lowest quintile of intake, those in the second and third quintiles of dietary fiber intake had a 7%-10% reduction in risk of all-cause mortality, and a 15%-17% reduction in the risk of mortality from other causes. Increasing consumption of fruits was also associated with a decreased risk of mortality for all-cause mortality by 9%-11%, and all cancer by 15–20%. Further, those in the third and fourth quintiles of vegetables intake had 11%-12% lower risk for CVD mortality.

Discussion
The results from the GCS further support the current recommendations on following a healthy diet containing proper amounts of fiber, vegetables, and fruits, as health-protective dietary items.

Conclusions
Higher intake of dietary fiber, fruits, and vegetables has the potential to reduce both overall and cause-specific mortality rates. However, additional cohort studies with larger sample size and long-term follow-up durations are required to establish these findings.
COVID-19 inpatient mortality in Brazil from 2020 to 2022: a cross-sectional overview study based on secondary data
Authors: Portela Margareth Crisóstomo , Martins Mônica , Lima Sheyla Maria Lemos , de Andrade Carla Lourenço Tavares , de Aguiar Pereira Claudia Cristina 
Published: November 2023

Abstract
Background
In Brazil, the COVID-19 pandemic found the universal and public Unified Health System (SUS) with problems accumulated over time, due, among other reasons, to low investments, and disparities in resource distribution. The preparedness and response of the healthcare system, involving the SUS and a private sector, was affected by large socioeconomic and healthcare access inequities. This work was aimed at offering an overview of COVID-19 inpatient mortality during the pandemic in Brazil, exploring factors associated with its variations and, specifically, differences across public, private (for-profit) and philanthropic (private non-profit) inpatient healthcare units, providers, and non-providers of services to the SUS.

Methods
This cross-sectional study used public secondary data. The main data source was the SIVEP-Gripe, which comprises data on severe acute respiratory illness records prospectively collected. We also employed the National Record of Health Establishments, the SUS’ Hospitalization Information System and municipalities' data from IBGE. We considered adult COVID-19 hospitalizations registered in SIVEP-Gripe from February 2020 to December 2022 in inpatient healthcare units with a minimum of 100 cases in the period. Data analyses explored the occurrence of inpatient mortality, employing general linear mixed models to identify the effects of patients', health care processes', healthcare units' and municipalities' characteristics on it.

Results
About 70% of the COVID-19 hospitalizations in Brazil were covered by the SUS, which attended the more vulnerable population groups and had worse inpatient mortality. In general, non-SUS private and philanthropic hospitals, mostly reimbursed by healthcare insurance plans accessible for more privileged socioeconomic classes, presented the best outcomes. Southern Brazil had the best performance among the macro-regions. Black and indigenous individuals, residents of lower HDI municipalities, and those hospitalized out of their residence city presented higher odds of inpatient mortality. Moreover, adjusted inpatient mortality rates were higher in the pandemic peak moments and were significantly reduced after COVID-19 vaccination reaching a reasonable coverage, from July 2021.

Conclusions
COVID-19 exposed socioeconomic and healthcare inequalities and the importance and weaknesses of SUS in Brazil. This work indicates the need to revert the disinvestment in the universal public system, a fundamental policy for reduction of inequities in the country.
Fe-doped carbon dots: a novel biocompatible nanoplatform for multi-level cancer therapy
Authors: Yang Mingxi , Li Haiqiu , Liu Xinchen , Huang Lei , Zhang Boya , Liu Kexuan , Xie Wangni , Cui Jing , Li Daowei , Lu Laijin , Sun Hongchen , Yang Bai 
Published: November 2023

Abstract
Background
Tumor treatment still remains a clinical challenge, requiring the development of biocompatible and efficient anti-tumor nanodrugs. Carbon dots (CDs) has become promising nanomedicines for cancer therapy due to its low cytotoxicity and easy customization.

Results
Herein, we introduced a novel type of “green” nanodrug for multi-level cancer therapy utilizing Fe-doped carbon dots (Fe-CDs) derived from iron nutrient supplement. With no requirement for target moieties or external stimuli, the sole intravenous administration of Fe-CDs demonstrated unexpected anti-tumor activity, completely suppressing tumor growth in mice. Continuous administration of Fe-CDs for several weeks showed no toxic effects in vivo, highlighting its exceptional biocompatibility. The as-synthesized Fe-CDs could selectively induce tumor cells apoptosis by BAX/Caspase 9/Caspase 3/PARP signal pathways and activate antitumoral macrophages by inhibiting the IL-10/Arg-1 axis, contributing to its significant tumor immunotherapy effect. Additionally, the epithelial-mesenchymal transition (EMT) process was inhibited under the treatment of Fe-CDs by MAPK/Snail pathways, indicating the capacity of Fe-CDs to inhibit tumor recurrence and metastasis.

Conclusions
A three-level tumor treatment strategy from direct killing to activating immunity to inhibiting metastasis was achieved based on “green” Fe-CDs. Our findings reveal the broad clinical potential of Fe-CDs as a novel candidate for anti-tumor nanodrugs and nanoplatform.
Pericytes are protective in experimental pneumococcal meningitis through regulating leukocyte infiltration and blood–brain barrier function
Authors: Teske Nina C. , Dyckhoff-Shen Susanne , Beckenbauer Paul , Bewersdorf Jan Philipp , Engelen-Lee Joo-Yeon , Hammerschmidt Sven , Kälin Roland E. , Pfister Hans-Walter , Brouwer Matthijs C. , Klein Matthias , Glass Rainer , van de Beek Diederik , Koedel Uwe 
Published: November 2023

Abstract
Background
Brain pericytes participate in the regulation of cerebral blood flow and the maintenance of blood–brain barrier integrity. Because of their perivascular localization, their receptor repertoire, and their potential ability to respond to inflammatory and infectious stimuli by producing various cytokines and chemokines, these cells are also thought to play an active role in the immune response to brain infections. This assumption is mainly supported by in vitro studies, investigations in in vivo disease models are largely missing. Here, we analysed the role of brain pericytes in pneumococcal meningitis, in vitro and in vivo in two animal models of pneumococcal meningitis.

Methods
Primary murine and human pericytes were stimulated with increasing concentrations of different serotypes of Streptococcus pneumoniae in the presence or absence of Toll-like receptor inhibitors and their cell viability and cytokine production were monitored. To gain insight into the role of pericytes in brain infection in vivo, we performed studies in a zebrafish embryo model of pneumococcal meningitis in which pericytes were pharmacologically depleted. Furthermore, we analyzed the impact of genetically induced pericyte ablation on disease progression, intracranial complications, and brain inflammation in an adult mouse model of this disease.

Results
Both murine and human pericytes reacted to pneumococcal exposure with the release of selected cytokines. This cytokine release is pneumolysin-dependent, TLR-dependent in murine (but not human) pericytes and can be significantly increased by macrophage-derived IL-1b. Pharmacological depletion of pericytes in zebrafish embryos resulted in increased cerebral edema and mortality due to pneumococcal meningitis. Correspondingly, in an adult mouse meningitis model, a more pronounced blood–brain barrier disruption and leukocyte infiltration, resulting in an unfavorable disease course, was observed following genetic pericyte ablation. The degree of leukocyte infiltration positively correlated with an upregulation of chemokine expression in the brains of pericyte-depleted mice.

Conclusions
Our findings show that pericytes play a protective role in pneumococcal meningitis by impeding leukocyte migration and preventing blood–brain barrier breaching. Thus, preserving the integrity of the pericyte population has the potential as a new therapeutic strategy in pneumococcal meningitis.
Ly6C-high monocytes alleviate brain injury in experimental subarachnoid hemorrhage in mice
Authors: Chen Huaijun , Xu Chaoran , Zeng Hanhai , Zhang Zhihua , Wang Ning , Guo Yinghan , Zheng Yonghe , Xia Siqi , Zhou Hang , Yu Xiaobo , Fu Xiongjie , Tang Tianchi , Wu Xinyan , Chen Zihang , Peng Yucong , Cai Jing , Li Jianru , Yan Feng , Gu Chi , Chen Gao , Chen Jingyin 
Published: November 2023

Abstract
Background
Subarachnoid hemorrhage (SAH) is an uncommon type of potentially fatal stroke. The pathophysiological mechanisms of brain injury remain unclear, which hinders the development of drugs for SAH. We aimed to investigate the pathophysiological mechanisms of SAH and to elucidate the cellular and molecular biological response to SAH-induced injury.

Methods
A cross-species (human and mouse) multiomics approach combining high-throughput data and bioinformatic analysis was used to explore the key pathophysiological processes and cells involved in SAH-induced brain injury. Patient data were collected from the hospital (n = 712). SAH was established in adult male mice via endovascular perforation, and flow cytometry, a bone marrow chimera model, qPCR, and microglial depletion experiments were conducted to explore the origin and chemotaxis mechanism of the immune cells. To investigate cell effects on SAH prognosis, murine neurological function was evaluated based on a modified Garcia score, pole test, and rotarod test.

Results
The bioinformatics analysis confirmed that inflammatory and immune responses were the key pathophysiological processes after SAH. Significant increases in the monocyte levels were observed in both the mouse brains and the peripheral blood of patients after SAH. Ly6C-high monocytes originated in the bone marrow, and the skull bone marrow contribute a higher proportion of these monocytes than neutrophils. The mRNA level of Ccl2 was significantly upregulated after SAH and was greater in CD11b-positive than CD11b-negative cells. Microglial depletion, microglial inhibition, and CCL2 blockade reduced the numbers of Ly6C-high monocytes after SAH. With CCR2 antagonization, the neurological function of the mice exhibited a slow recovery. Three days post-SAH, the monocyte-derived dendritic cell (moDC) population had a higher proportion of TNF-α-positive cells and a lower proportion of IL-10-positive cells than the macrophage population. The ratio of moDCs to macrophages was higher on day 3 than on day 5 post-SAH.

Conclusions
Inflammatory and immune responses are significantly involved in SAH-induced brain injury. Ly6C-high monocytes derived from the bone marrow, including the skull bone marrow, infiltrated into mouse brains via CCL2 secreted from microglia. Moreover, Ly6C-high monocytes alleviated neurological dysfunction after SAH.
Safety and efficacy of a modified WALANT technique using undiluted adrenaline during open surgical carpal tunnel release: a prospective report of 308 procedures
Authors: Kotb Mohamed Mostafa , Omar Usama Farghaly , Khalifa Ahmed A. 
Published: November 2023

Abstract
Purpose
The current study aimed to report on the safety and efficacy of utilizing a modified WALANT (mWALANT) technique during open surgical carpal tunnel release (CTR), where we used undiluted epinephrine compared to the originally described WALANT technique.

Methods
From January 2015 till the end of June 2021, 200 patients (175 (87.5%) were females) who presented with carpal tunnel syndrome, either bilateral (108 (54%) patients) or unilateral (92 (46%)) were included, formulating a total of 308 procedures. Open surgical CTR was performed as a daycare procedure by the same surgeon. The mWALANT injectable mixture was prepared by mixing 8 CC of 2% lidocaine HCl + 1 CC of 0.25 mg/1 ml epinephrine without dilution (2.5 times the concentration used in the original WALANT technique). The injection was performed before draping.

Results
The patients’ average age at surgery was 42.88 ± 13.03 years old; they were followed up for an average of 31 ± 17.17 months. The average operative time was 9.5 ± 1.87 min. None (0.0%) of the patients needed top-up of local anesthesia or shift into general anesthesia, and no (0.0%) patients needed postoperative hospital stay. The average VAS during the surgical procedure was 2.5 ± 2.1, mainly reported during infiltration of the local anesthesia; no patients reported discomfort during the surgical procedure itself. 180 (90%) patients reported a full return to their usual preoperative ADL after an average of 4.7 ± 1.2 weeks. No (0.0%) postoperative fingers ischemic or temperature changes. Two (1%) patients experienced an adrenaline rush in the form of tachycardia that needed sedation and close monitoring by the anesthesiologist; they were discharged on the same day. One (0.5%) patient (who had uncontrolled diabetes mellitus) showed a superficial wound infection which resolved after conservative management.

Conclusions
Using undiluted epinephrine during the mWALANT technique is safe and effective. There is no need to wait until the drugs fully function, and no epinephrine-related complications were encountered apart from occasional adrenaline rush symptoms.
Most patients with an increased risk for sepsis-related morbidity or death do not recognize sepsis as a medical emergency: results of a survey study using case vignettes
Authors: Born Sebastian , Fleischmann-Struzek Carolin , Abels Wiltrud , Piedmont Silke , Neugebauer Edmund , Reinhart Konrad , Toubekis Evjenia , Wegwarth Odette , Schwarzkopf Daniel 
Published: November 2023

Abstract
Background
Sepsis is a medical emergency with potentially life-threatening consequences. Patients play a crucial role in preventing and recognizing sepsis at an early stage. The understanding of risk groups’ sepsis knowledge and their ability to use this knowledge to recognize sepsis as an emergency is incomplete.

Methods
We conducted a cross-sectional survey in Germany and included a sample of 740 persons stratified by age (< 60 years,  ≥ 60 years), specific chronic diseases (e.g. diabetes, chronic diseases, cancer), and region (Berlin/Brandenburg vs. other federal states of Germany). Standardized questionnaires were administered by a market research institute through online, telephone, or face-to-face methods. We assessed sepsis knowledge through a series of questions and the ability to recognize sepsis as an emergency through five case vignettes. To identify predictors of sepsis knowledge and the ability to recognize sepsis as a medical emergency, we conducted multiple linear regressions.

Results
Of the 36 items on sepsis knowledge, participants answered less than 50 per cent correctly (mean 44.1%; standard deviation (SD) 20.1). Most patients knew that sepsis is a defensive host response to infection (75.9%), but only 30.8% knew that vaccination can prevent infections that lead to sepsis. Across the five vignettes, participants identified sepsis as an emergency in only 1.33 of all cases on average (SD = 1.27). Sepsis knowledge was higher among participants who were older, female, and more highly educated and who reported more extensive health information seeking behaviour. The ability to recognize sepsis as an emergency was higher among younger participants, participants without chronic diseases, and participants with higher health literacy, but it was not significantly associated with sepsis knowledge.

Conclusions
Risk groups showed low levels of knowledge regarding the preventive importance of vaccination and a low ability to recognize sepsis as a medical emergency. Higher levels of sepsis knowledge alone were not sufficient to improve the ability to identify sepsis as a medical emergency. It is crucial to develop effective educational strategies—especially for persons with lower education levels and infrequent health information seeking behaviour—that not only transfer but also facilitate the choice of appropriate actions, such as seeking timely emergency care.
Trial registration: DRKS00024561. Registered 9 March 2021.
Head and neck INI1-deficient carcinoma without primary: a case report
Authors: Dubray-Vautrin Antoine , Ghanem Wahib , Bozec Laurence , Gonin Julie , Choussy Olivier 
Published: November 2023

Abstract
Background
SMARCB1, also known as INI1, is a member of a large protein complex involved in chromatin remodeling and thus the regulation of gene expression. It is located on chromosome 22q11.2. SMARCB1 tumors have been found in various locations, including the sinonasal region, gastrointestinal tract, central nervous system (in atypical teratoid and rhabdoid tumors), and perirenal region (in malignant rhabdoid tumors) in both adults and children.

Case presentation
We describe here the first case in the literature of an INI1-deficient neck carcinoma without a primary tumor managed with surgical therapy and neck dissection in a young Caucasian woman of 29 years old, followed by chemotherapy before radiotherapy, with regional control after 18 months of follow-up. Histologic analysis showed an undifferentiated carcinoma without glandular or epidermoid differentiation. Biomolecular analysis of the tumor revealed a homozygous deletion of the SMARCB1 gene on RNA sequencing.

Conclusion
Research of INI1 deletion should be performed for undifferentiated carcinoma of young patients because of possibilities of molecular therapies such as autophagy inhibitors or proteasome inhibitors could be used in clinical trials.
Extracellular vesicle-based liquid biopsy biomarkers and their application in precision immuno-oncology
Authors: Asleh Karama , Dery Valerie , Taylor Catherine , Davey Michelle , Djeungoue-Petga Marie-Ange , Ouellette Rodney J. 
Published: November 2023

AbstractWhile the field of precision oncology is rapidly expanding and more targeted options are revolutionizing cancer treatment paradigms, therapeutic resistance particularly to immunotherapy remains a pressing challenge. This can be largely attributed to the dynamic tumor-stroma interactions that continuously alter the microenvironment. While to date most advancements have been made through examining the clinical utility of tissue-based biomarkers, their invasive nature and lack of a holistic representation of the evolving disease in a real-time manner could result in suboptimal treatment decisions. Thus, using minimally-invasive approaches to identify biomarkers that predict and monitor treatment response as well as alert to the emergence of recurrences is of a critical need. Currently, research efforts are shifting towards developing liquid biopsy-based biomarkers obtained from patients over the course of disease. Liquid biopsy represents a unique opportunity to monitor intercellular communication within the tumor microenvironment which could occur through the exchange of extracellular vesicles (EVs). EVs are lipid bilayer membrane nanoscale vesicles which transfer a plethora of biomolecules that mediate intercellular crosstalk, shape the tumor microenvironment, and modify drug response. The capture of EVs using innovative approaches, such as microfluidics, magnetic beads, and aptamers, allow their analysis via high throughput multi-omics techniques and facilitate their use for biomarker discovery. Artificial intelligence, using machine and deep learning algorithms, is advancing multi-omics analyses to uncover candidate biomarkers and predictive signatures that are key for translation into clinical trials. With the increasing recognition of the role of EVs in mediating immune evasion and as a valuable biomarker source, these real-time snapshots of cellular communication are promising to become an important tool in the field of precision oncology and spur the recognition of strategies to block resistance to immunotherapy. In this review, we discuss the emerging role of EVs in biomarker research describing current advances in their isolation and analysis techniques as well as their function as mediators in the tumor microenvironment. We also highlight recent lung cancer and melanoma studies that point towards their application as predictive biomarkers for immunotherapy and their potential clinical use in precision immuno-oncology.