bluuebunny/crossref_metadata_2025_split huggingface dataset:
The RP11-417E7.1/THBS2 signaling pathway promotes colorectal cancer metastasis by activating the Wnt/β-catenin pathway and facilitating exosome-mediated M2 macrophage polarization
Authors: Liu Yunze , Lv Heng , Liu Xin , Xu Lei , Li Tiankang , Zhou Hui , Zhu Hongmei , Hao Chuanchuan , Lin Changwei , Zhang Yi 
Published: July 2024

Abstract
Background
Metastasis is the major cause of colorectal cancer (CRC) mortality. Emerging evidence suggests that long noncoding RNAs (lncRNAs) drive cancer metastasis and that their regulatory pathways could be targeted for preventing metastasis. However, the underlying mechanisms of lncRNAs in CRC metastasis remain poorly understood.

Methods
Microarray analysis was used to screen for differentially expressed lncRNAs. Transwell assays, fibronectin cell adhesion assays, and mouse metastasis models were utilized to evaluate the metastatic capacities of CRC in vitro and in vivo. Chromatin isolation by RNA purification, chromatin immunoprecipitation and chromosome conformation capture were applied to investigate the underlying mechanism involved. qRT‒PCR and transmission electron microscopy were performed to confirm macrophage polarization and the presence of cancer-derived exosomes.

Results
The lncRNA RP11-417E7.1 was screened and identified as a novel metastasis-associated lncRNA that was correlated with a poor prognosis. RP11-417E7.1 enhances the metastatic capacity of CRC cells in vivo and in vitro. Mechanistically, RP11-417E7.1 binding with High mobility group A1 (HMGA1) promotes neighboring thrombospondin 2 (THBS2) transcription via chromatin loop formation between its promoter and enhancer, which activates the Wnt/β-catenin signaling pathway and facilitates CRC metastasis. Furthermore, exosomes derived from CRC cells transport THBS2 into macrophages, thereby inducing the M2 polarization of macrophages to sustain the prometastatic microenvironment. Notably, netropsin, a DNA-binding drug, suppresses chromatin loop formation mediated by RP11-417E7.1 at the THBS2 locus and significantly inhibits CRC metastasis in vitro and in vivo.

Conclusions
This study revealed the novel prometastatic function and mechanism of the lncRNA RP11-417E7.1, which provides a potential prognostic indicator and therapeutic target in CRC.
Targeted proteomics of plasma extracellular vesicles uncovers MUC1 as combinatorial biomarker for the early detection of high-grade serous ovarian cancer
Authors: Cooper Tyler T. , Dieters-Castator Dylan Z. , Liu Jiahui , Siegers Gabrielle M. , Pink Desmond , Veliz Lorena , Lewis John D. , Lagugné-Labarthet François , Fu Yangxin , Steed Helen , Lajoie Gilles A. , Postovit Lynne-Marie 
Published: July 2024

Abstract
Background
The five-year prognosis for patients with late-stage high-grade serous carcinoma (HGSC) remains dismal, underscoring the critical need for identifying early-stage biomarkers. This study explores the potential of extracellular vesicles (EVs) circulating in blood, which are believed to harbor proteomic cargo reflective of the HGSC microenvironment, as a source for biomarker discovery.

Results
We conducted a comprehensive proteomic profiling of EVs isolated from blood plasma, ascites, and cell lines of patients, employing both data-dependent (DDA) and data-independent acquisition (DIA) methods to construct a spectral library tailored for targeted proteomics. Our investigation aimed at uncovering novel biomarkers for the early detection of HGSC by comparing the proteomic signatures of EVs from women with HGSC to those with benign gynecological conditions. The initial cohort, comprising 19 donors, utilized DDA proteomics for spectral library development. The subsequent cohort, involving 30 HGSC patients and 30 control subjects, employed DIA proteomics for a similar purpose. Support vector machine (SVM) classification was applied in both cohorts to identify combinatorial biomarkers with high specificity and sensitivity (ROC-AUC > 0.90). Notably, MUC1 emerged as a significant biomarker in both cohorts when used in combination with additional biomarkers. Validation through an ELISA assay on a subset of benign (n = 18), Stage I (n = 9), and stage II (n = 9) plasma samples corroborated the diagnostic utility of MUC1 in the early-stage detection of HGSC.

Conclusions
This study highlights the value of EV-based proteomic analysis in the discovery of combinatorial biomarkers for early ovarian cancer detection.
Prioritising deteriorating patients using time-to-event analysis: prediction model development and internal–external validation
Authors: Blythe Robin , Parsons Rex , Barnett Adrian G. , Cook David , McPhail Steven M. , White Nicole M. 
Published: July 2024

Abstract
Background
Binary classification models are frequently used to predict clinical deterioration, however they ignore information on the timing of events. An alternative is to apply time-to-event models, augmenting clinical workflows by ranking patients by predicted risks. This study examines how and why time-to-event modelling of vital signs data can help prioritise deterioration assessments using lift curves, and develops a prediction model to stratify acute care inpatients by risk of clinical deterioration.

Methods
We developed and validated a Cox regression for time to in-hospital mortality. The model used time-varying covariates to estimate the risk of clinical deterioration. Adult inpatient medical records from 5 Australian hospitals between 1 January 2019 and 31 December 2020 were used for model development and validation. Model discrimination and calibration were assessed using internal–external cross validation. A discrete-time logistic regression model predicting death within 24 h with the same covariates was used as a comparator to the Cox regression model to estimate differences in predictive performance between the binary and time-to-event outcome modelling approaches.

Results
Our data contained 150,342 admissions and 1016 deaths. Model discrimination was higher for Cox regression than for discrete-time logistic regression, with cross-validated AUCs of 0.96 and 0.93, respectively, for mortality predictions within 24 h, declining to 0.93 and 0.88, respectively, for mortality predictions within 1 week. Calibration plots showed that calibration varied by hospital, but this can be mitigated by ranking patients by predicted risks.

Conclusion
Time-varying covariate Cox models can be powerful tools for triaging patients, which may lead to more efficient and effective care in time-poor environments when the times between observations are highly variable.
Biomarkers in pulmonary infections: a clinical approach
Authors: Póvoa Pedro , Coelho Luís , Cidade José Pedro , Ceccato Adrian , Morris Andrew Conway , Salluh Jorge , Nobre Vandack , Nseir Saad , Martin-Loeches Ignacio , Lisboa Thiago , Ramirez Paula , Rouzé Anahita , Sweeney Daniel A. , Kalil Andre C. 
Published: July 2024

AbstractSevere acute respiratory infections, such as community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia, constitute frequent and lethal pulmonary infections in the intensive care unit (ICU). Despite optimal management with early appropriate empiric antimicrobial therapy and adequate supportive care, mortality remains high, in part attributable to the aging, growing number of comorbidities, and rising rates of multidrug resistance pathogens. Biomarkers have the potential to offer additional information that may further improve the management and outcome of pulmonary infections. Available pathogen-specific biomarkers, for example, Streptococcus pneumoniae urinary antigen test and galactomannan, can be helpful in the microbiologic diagnosis of pulmonary infection in ICU patients, improving the timing and appropriateness of empiric antimicrobial therapy since these tests have a short turnaround time in comparison to classic microbiology. On the other hand, host-response biomarkers, for example, C-reactive protein and procalcitonin, used in conjunction with the clinical data, may be useful in the diagnosis and prediction of pulmonary infections, monitoring the response to treatment, and guiding duration of antimicrobial therapy. The assessment of serial measurements overtime, kinetics of biomarkers, is more informative than a single value. The appropriate utilization of accurate pathogen-specific and host-response biomarkers may benefit clinical decision-making at the bedside and optimize antimicrobial stewardship.
Expression, characterization, and application of human-like recombinant gelatin
Authors: Song Xiaoping , Chu Tao , Shi Wanru , He Jingyan 
Published: July 2024

AbstractGelatin is a product obtained through partial hydrolysis and thermal denaturation of collagen, belonging to natural biopeptides. With irreplaceable biological functions in the field of biomedical science and tissue engineering, it has been widely applied. The amino acid sequence of recombinant human-like gelatin was constructed through a newly designed hexamer composed of six protein monomer sequences in series, with the minimum repeating unit being the characteristic Gly-X-Y sequence found in type III human collagen α1 chain. The nucleotide sequence was subsequently inserted into the genome of Pichia pastoris to enable soluble secretion expression of recombinant gelatin. At the shake flask fermentation level, the yield of recombinant gelatin is up to 0.057 g/L, and its purity can rise up to 95% through affinity purification. It was confirmed in the molecular weight determination and amino acid analysis that the amino acid composition of the obtained recombinant gelatin is identical to that of the theoretically designed. Furthermore, scanning electron microscopy revealed that the freeze-dried recombinant gelatin hydrogel exhibited a porous structure. After culturing cells continuously within these gelatin microspheres for two days followed by fluorescence staining and observation through confocal laser scanning microscopy, it was observed that cells clustered together within the gelatin matrix, exhibiting three-dimensional growth characteristics while maintaining good viability. This research presents promising prospects for developing recombinant gelatin as a biomedical material.
Health Problems of Professional Ballet Dancers: an Analysis of 1627 Weekly Self-Reports on Injuries, Illnesses and Mental Health Problems During One Season
Authors: Junge Astrid , Hauschild Anja , Stubbe Janine H. , van Rijn Rogier M. 
Published: July 2024

Abstract
Background
Several studies have investigated injuries of (pre-)professional ballet dancers, however most used a medical-attention and/or time-loss definition and did not analyse the prevalence of all health problems. The aim was to analyse the frequency and characteristics of all self-reported physical and mental health complaints (i.e. injuries, illnesses and mental health problems) of professional ballet dancers during one season.

Methods
Three professional ballet companies were prospectively monitored weekly during one season with the Performing artist and Athlete Health Monitor (PAHM). Numerical rating scales (ranging 0–10) were used for severity of musculoskeletal pain, all health problems and impairment of the ability to dance at full potential in the previous seven days. If dancers rated the severity of their health problems or their impairment greater than 0, they were asked to answer specific questions on the characteristics of each health problem.

Results
Over a period of 44 weeks, 57 dancers (57.9% female) filled in 1627 weekly reports (response rate of 64.9%), in which 1020 (62.7%) health problem were registered. The dancers reported musculoskeletal pain in 82.2% of the weeks. They felt that their ability to dance at their full potential was affected due to a health problem in about every second week (52.6%) or on at least 29.1% of the days documented in the weekly reports. Almost all dancers (96.5%) reported at least one injury, almost two thirds (64.9%) an illness and more than a quarter (28.1%) a mental health problem. On average, every dancer reported 5.6 health problems during the season. Most of the 320 health problems were injuries (73.1%), 16.9% illnesses and 10.0% mental health problems. Injuries affected mainly ankle, thigh, foot, and lower back and were mostly incurred during rehearsal (41.6%) or training (26.1%). The most frequent subjective reasons of injury were “too much workload” (35.3%), “tiredness/exhaustion” (n = 22.4%) and “stress/overload/insufficient regeneration” (n = 21.6%).

Conclusion
Preventive interventions are urgently required to reduce the prevalence of health problems and especially injuries of professional dancers. Injury prevention measures should regard the balance of the load capacity of professional dancers and the workload in training, rehearsals and performances.
Systematics and phylogeny of the entomopathogenic nematobacterial complexes Steinernema–Xenorhabdus and Heterorhabditis–Photorhabdus
Authors: Půža Vladimír , Machado Ricardo A. R. 
Published: July 2024

AbstractEntomopathogenic nematodes of the genera Steinernema and Heterorhabditis, along with their bacterial symbionts from the genera Xenorhabdus and Photorhabdus, respectively, are important biological control agents against agricultural pests. Rapid progress in the development of genomic tools has catalyzed a transformation of the systematics of these organisms, reshaping our understanding of their phylogenetic and cophlylogenetic relationships. In this review, we discuss the major historical events in the taxonomy and systematics of this group of organisms, highlighting the latest advancements in these fields. Additionally, we synthesize information on nematode–bacteria associations and assess the existing evidence regarding their cophylogenetic relationships.
From allegory to conceptualization, hypothesis and finally evidences: Alzheimer’s dementia, Parkinson's disease "gut–brain axis" and their preclinical phenotype
Authors: Dubey Souvik , Ghosh Ritwik , Dubey Mahua Jana , Sengupta Samya , Das Shambaditya 
Published: July 2024

AbstractResearchers are constantly trying to develop therapeutic targets in neurodegenerative disorders like Alzheimer's dementia and Parkinson's disease. Despite enormous endeavors, there are several unmet needs. Several contradictory pathophysiological basis of neurodegenerative disorders are considered to be one of the most important cause underpinning. "Gut–brain dysbiosis" has been considered as one of the most crucial link to explore. Contemporary researches have suggested similar pathophysiological mechanisms underpinning Alzheimer's dementia and Parkinson's disease. "Gut–brain dysbiosis" may be the missing thread connecting Alzheimer's dementia and Parkinson's disease prior to the expression of their overt clinical phenotype. Recognition of preclinical phenotype of Alzheimer's dementia and Parkinson's disease have much broader perspective as it will help in building robust therapeutics at the earliest. Authors herein critically analyze the pathophysiological basis of Alzheimer's dementia and Parkinson's disease in relationship with "Gut–brain dysbiosis" and also try to search the preclinical phenotype/s of Alzheimer's dementia and Parkinson's disease pivoting around the Freudian hypothesis.
A three-years survey of microbial contaminants in industrial hemp inflorescences from two Italian cultivation sites
Authors: Spampinato Gloria , Candeliere Francesco , Amaretti Alberto , Paris Roberta , Montanari Massimo , Virzì Nino , Strani Lorenzo , Citti Cinzia , Cannazza Giuseppe , Rossi Maddalena , Raimondi Stefano 
Published: July 2024

Abstract
Background
The use of industrial Cannabis sativa L. for recreational, cosmeceutical, nutraceutical, and medicinal purposes has gained momentum due to its rich content of valuable phytochemicals, such as cannabidiol (CBD) and cannabigerol (CBG). However, there are concerns regarding the risk of microbial contamination in plants grown outside controlled environments. Microbes associated with hemp can be either epiphytes or endophytes and may pose a risk of infectious illness for humans.

Methods
Seven Italian hemp genotypes, including Bernabeo, Carmagnola, Carmaleonte, Codimono, CS, Eletta Campana, and Fibranova, were cultivated in two distinct geographic locations, Catania and Rovigo, for three consecutive years from 2019 to 2021. Total aerobic microbes (TAMC), total combined yeasts/moulds (TYMC), the presence of bile-tolerant Gram-negative bacteria, and the absence of Escherichia coli and Salmonella spp. were evaluated and compared. The main phytocannabinoid content was measured and correlated with microbial contamination.

Results
Most samples analyzed in this study did not meet the European Pharmacopoeia microbiological limits. The detection of potential pathogens, such as E. coli and Salmonella spp., in the samples indicates that the use of inflorescences may represent a possible source of infection. Microbial contamination varied among harvesting seasons and production sites, with agroclimatic conditions influencing microbial load and composition. The presence of potentially pathogenic bacteria was less associated with seasonal climate variability and more likely affected by sporadic contamination from external sources. CBD concentration exhibited a negative correlation with bile-tolerant Gram-negative bacteria and total yeasts/moulds levels. Samples with lower CBD content were more contaminated than those with higher CBD levels, suggesting a potential protective effect of this phytochemical on the plant.

Conclusions
The threshing residues (inflorescences, floral bracts, and leaves) of industrial hemp varieties represent a valuable product and a source of beneficial phytochemicals that warrants further exploration. While post-harvest sterilization methods may reduce microbiological risks, they may also degrade heat- and light-sensitive bioactive phytochemicals. The most promising strategy involves implementing best agronomic practices to maintain healthy and uncontaminated cultures. Rigorous monitoring and quality certification protocols are essential to mitigate the microbiological risk associated with the consumption of hemp-derived products.
Post-Transplant Cyclophosphamide–Based Graft-Versus-Host Disease Prophylaxis Attenuates Disparity in Outcomes Between Use of Matched or Mismatched Unrelated Donors
Authors: Shaffer Brian C. , Gooptu Mahasweta , DeFor Todd E. , Maiers Martin , Bolaños-Meade Javier , Abboud Ramzi , Briggs Adrienne D. , Khimani Farhad , Modi Dipenkumar , Newcomb Richard , Shpall Elizabeth J. , Bupp Caitrin , Spellman Stephen R. , Stefanski Heather E. , Shaw Bronwen E. , Auletta Jeffery J. , Devine Steven M. , Jimenez Jimenez Antonio M. , Al Malki Monzr M. 
Published: July 2024

PURPOSE
Access to allogeneic hematopoietic cell transplantation (HCT) remains limited among persons of non-European ancestry if human leukocyte antigen (HLA) matching is required. We evaluated whether post-transplant cyclophosphamide (PTCy)–based graft-versus-host disease (GVHD) prophylaxis improved HCT outcomes with HLA-matched unrelated donor (MUD) and mismatched unrelated donor (MMUD) HCT when compared with calcineurin inhibitor (CNI)–based prophylaxis.

METHODS
Three-year overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were compared between adult recipients undergoing initial MUD or single HLA locus MMUD HCT with either PTCy- or CNI-based prophylaxis who were reported to the Center for International Blood and Marrow Transplant Research between 2017 and 2021.

RESULTS

Included were 10,025 HCT recipients (7,272 recipients of MUD with CNI, 1,681 MUD with PTCy, 613 MMUD with CNI, and 459 MMUD with PTCy) who underwent HCT for acute leukemia (70.9%) or myelodysplastic syndromes (29.2%). Median patient age was 60.7 years (range, 18.0-82.7) and median follow-up was 36.6 (range, 3.0-77.8) months. When compared with MUD HCT with PTCy, MMUD HCT with PTCy had similar OS (hazard ratio [HR], 0.96 [95% CI, 0.823 to 1.11];
P
= .60) and GRFS (HR, 0.90 [0.79 to 1.02];
P
= .1). When compared with MUD HCT with CNI, OS was improved after MUD HCT with PTCy (HR, 0.88 [0.80 to 0.96];
P
= .004) and GRFS was improved with PTCy after either MUD (HR, 0.61 [0.57 to 0.66];
P
< .0001) or MMUD (HR, 0.68 [0.60 to 0.76];
P
< .0001) HCT. Benefit from PTCy was independent of patient ancestry. Global registry level analysis demonstrated that inclusion of MMUD increased donor availability regardless of recipient ancestry.

CONCLUSION
Use of PTCy results in comparable OS and GRFS using either MUD or MMUD HCT, expanding access to HCT for patients from all racial and ethnic ancestry groups.
Chemical genetic screens reveal defective lysosomal trafficking as synthetic lethal with NF1 loss
Authors: Bouley Stephanie J. , Grassetti Andrew V. , Allaway Robert J. , Wood Matthew D. , Hou Helen W. , Burdon Dasbach India R. , Seibel William , Wu Jimmy , Gerber Scott A. , Dragnev Konstantin H. , Walker James A. , Sanchez Yolanda 
Published: July 2024

ABSTRACT
Neurofibromatosis type 1, a genetic disorder caused by pathogenic germline variations in NF1, predisposes individuals to the development of tumors, including cutaneous and plexiform neurofibromas (CNs and PNs), optic gliomas, astrocytomas, juvenile myelomonocytic leukemia, high-grade gliomas and malignant peripheral nerve sheath tumors (MPNSTs), which are chemotherapy- and radiation-resistant sarcomas with poor survival. Loss of NF1 also occurs in sporadic tumors, such as glioblastoma (GBM), melanoma, breast, ovarian and lung cancers. We performed a high-throughput screen for compounds that were synthetic lethal with NF1 loss, which identified several leads, including the small molecule Y102. Treatment of cells with Y102 perturbed autophagy, mitophagy and lysosome positioning in NF1-deficient cells. A dual proteomics approach identified BLOC-one-related complex (BORC), which is required for lysosome positioning and trafficking, as a potential target of Y102. Knockdown of a BORC subunit using siRNA recapitulated the phenotypes observed with Y102 treatment. Our findings demonstrate that BORC might be a promising therapeutic target for NF1-deficient tumors.
Η χρήση και αποτελεσματικότητα του video modeling στην εκπαίδευση δραστηριοτήτων καθημερινής ζωής σε παιδιά με Διαταραχή Αυτιστικού Φάσματος ηλικίας 4-7 ετών
Authors: Βούλγαρης Ηλίας , Σοφός Αλιβίζος (Λοΐζος) 
Published: July 2024

Η παρούσα πειραματική ερευνητική εργασία διερεύνησε τη χρήση και την αποτελεσματικότητα της μοντελοποίησης βίντεο (video modeling) ως θεραπευτική και εκπαιδευτική παρέμβαση για τη βελτίωση 2 δραστηριοτήτων καθημερινής ζωής (ΔΚΖ) (βούρτσισμα δονιτών και τοποθέτησης κάλτσας/παπουτσιού) παιδιών που έχουν διαγνωστεί με διαταραχή αυτιστικού φάσματος (ΔΑΦ). Σκοπός της μελέτης ήταν να διερευνήσει την επίδραση της παρέμβασης μοντελοποίησης βίντεο στην απόκτηση και διατήρηση των δεξιοτήτων ΔΚΖ σε αυτόν τον πληθυσμό.
Ο σχεδιασμός της μελέτης περιελάμβανε μια τυχαιοποιημένη ελεγχόμενη δοκιμή (Randomized Controlled Trial-RCT) που περιλαμβάνει προ-δοκιμή, μετα-δοκιμή και αξιολόγηση της φάσης μεταφοράς και γενίκευσης για την αποτελεσματικότητα της μοντελοποίησης βίντεο σε σύγκριση με τις παραδοσιακές μεθόδους διδασκαλίας. Συλλέχθηκε ένα δείγμα (10) παιδιών (4 έως 7 ετών) με διάγνωση ΔΑΦ και κατανεμήθηκαν τυχαία σε μια πειραματική ομάδα και μια ομάδα ελέγχου, αφού πρώτα διενεργήθηκαν οι απαραίτητοι έλεγχοι τόσο για το επίπεδο των συμμετεχόντων με την χρήση σταθμισμένων κλιμάκων και εργαλείων αξιολόγησης, όσο και για να εξασφαλισθεί η ισοδυναμία των ομάδων.
Ποσοτικά δεδομένα συλλέχθηκαν με τη χρήση τυποποιημένων εργαλείων αξιολόγησης πριν από την παρέμβαση, μετά την παρέμβαση και κατά τη διάρκεια των συνεδριών για τη μέτρηση της απόκτησης, της γενίκευσης και της διατήρησης των δεξιοτήτων. Συλλέχθηκαν επίσης και ποιοτικά δεδομένα σχετικά με τη χρησιμότητα και την αποτελεσματικότητα της βιντεομοντελοποίησης.
Τα αποτελέσματα κατέδειξαν την υπεροχή της παρέμβασης μοντελοποίησης με βίντεο και στις 2 δραστηριότητες που μελετήθηκαν, καθώς και στην αποτελεσματικότερη μεταφορά και γενίκευση αυτών των δραστηριοτήτων σε διαφορετικά περιβάλλοντα.