bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing biomarkers for accurate ependymoma diagnosis, prognostication, and stratification within International Clinical Trials: A BIOMECA study
Authors: Chapman Rebecca J , Ghasemi David R , Andreiuolo Felipe , Zschernack Valentina , Espariat Arnault Tauziede , Buttarelli Francesca R , Giangaspero Felice , Grill Jacques , Haberler Christine , Paine Simon M L , Scott Ian , Jacques Thomas S , Sill Martin , Pfister Stefan , Kilday John-Paul , Leblond Pierre , Massimino Maura , Witt Hendrik , Modena Piergiorgio , Varlet Pascale , Pietsch Torsten , Grundy Richard G , Pajtler Kristian W , Ritzmann Timothy A 
Published: March 2023

Abstract

Background
Accurate identification of brain tumor molecular subgroups is increasingly important. We aimed to establish the most accurate and reproducible ependymoma subgroup biomarker detection techniques, across 147 cases from International Society of Pediatric Oncology (SIOP) Ependymoma II trial participants, enrolled in the pan-European “Biomarkers of Ependymoma in Children and Adolescents (BIOMECA)” study.

Methods
Across 6 European BIOMECA laboratories, we evaluated epigenetic profiling (DNA methylation array); immunohistochemistry (IHC) for nuclear p65-RELA, H3K27me3, and Tenascin-C; copy number analysis via fluorescent in situ hybridization (FISH) and MLPA (1q, CDKN2A), and MIP and DNA methylation array (genome-wide copy number evaluation); analysis of ZFTA- and YAP1-fusions by RT-PCR and sequencing, Nanostring and break-apart FISH.

Results
DNA Methylation profiling classified 65.3% (n = 96/147) of cases as EPN-PFA and 15% (n = 22/147) as ST-ZFTA fusion-positive. Immunohistochemical loss of H3K27me3 was a reproducible and accurate surrogate marker for EPN-PFA (sensitivity 99%–100% across 3 centers). IHC for p65-RELA, FISH, and RNA-based analyses effectively identified ZFTA- and YAP—fused supratentorial ependymomas. Detection of 1q gain using FISH exhibited only 57% inter-center concordance and low sensitivity and specificity while MIP, MLPA, and DNA methylation-based approaches demonstrated greater accuracy.

Conclusions
We confirm, in a prospective trial cohort, that H3K27me3 immunohistochemistry is a robust EPN-PFA biomarker. Tenascin-C should be abandoned as a PFA marker. DNA methylation and MIP arrays are effective tools for copy number analysis of 1q gain, 6q, and CDKN2A loss while FISH is inadequate. Fusion detection was successful, but rare novel fusions need more extensive technologies. Finally, we propose test sets to guide future diagnostic approaches.
Patients’ Perceptions Regarding the Relevance of Items Contained in the Functional Assessment of Cancer Therapy Kidney Symptom Index-19
Authors: Bergerot Cristiane Decat , Malhotra Jasnoor , Bergerot Paulo , Philip Errol J , Castro Daniela V , Hsu JoAnn , Mota Augusto Cesar de Andrade , Cardoso de Azeredo Andressa , Neto João Nunes de Matos , Hutson Thomas , Grünwald Viktor , Bex Axel , Psutka Sarah P , Rini Brian , Plimack Elizabeth R , Master Viraj , Albiges Laurence , Choueiri Toni K , Pal Sumanta , Powles Thomas 
Published: March 2023

Abstract

Background
There is a lack of consensus regarding the optimal method of assessing health-related quality of life (HR-QOL) among patients with metastatic renal cell carcinoma (mRCC). This study explored the perceived relevance of items that make up the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19), as judged by patients with mRCC.

Methods
This was a multinational cross-sectional survey. Eligible patients responded to a questionnaire composed of 18 items that assessed the perceived relevance of each item in the FKSI-19 questionnaire. Open-ended questions assessed additional issues deemed relevant by patients. Responses were grouped as relevant (scores 2-5) or nonrelevant (score 1). Descriptive statistics were collated, and open-ended questions were analyzed and categorized into descriptive categories. Spearman correlation statistics were used to test the association between relevance and clinical characteristics.

Results
A total of 151 patients were included (gender: 78.1 M, 21.9F; median age: 64; treatment: 38.4 immunotherapy, 29.8 targeted therapy, 13.9 immuno-TKI combination therapy) in the study. The most relevant questions evaluated fatigue (77.5), lack of energy (72.2), and worry that their condition will get worse (71.5). Most patients rated blood in urine (15.2), fevers (16.6), and lack of appetite (23.2) as least relevant. Qualitative analysis of open-ended questions revealed several themes, including emotional and physical symptoms, ability to live independently, effectiveness of treatment, family, spirituality, and financial toxicity.

Conclusion
There is a need to refine widely used HR-QOL measures that are employed among patients diagnosed with mRCC treated with contemporary therapies. Guidance was provided for the inclusion of more relevant items to patients’ cancer journey.
Regulatory Issues: PMDA – Review of Sakigake Designation Products: Oncolytic Virus Therapy with Delytact Injection (Teserpaturev) for Malignant Glioma
Authors: Maruyama Yoshiaki , Sakurai Akira , Noda Shinichi , Fujiwara Yasuhiro , Okura Narumi , Takagi Toshinori , Asano Junichi , Honda Futaba 
Published: March 2023

Abstract
In June 2021, the Ministry of Health, Labor and Welfare approved Delytact Injection as a regenerative medical product for oncolytic virus therapy. The active substance of Delytact Injection is teserpaturev, a genetically engineered herpes simplex virus type 1 (strain F) in which the α47 gene and both copies of the γ34.5 gene have been deleted and the infected cell protein 6 (ICP6) gene has been inactivated by the insertion of the lacZ gene from Escherichia coli. Delytact Injection, when intratumorally administered to patients with malignant glioma, is expected to exert the following effects: (1) the mutant virus selectively replicates in tumor cells and destroys the infected cells through the replication process, exerting a cytocidal effect, and (2) the administration leads to induction of tumor-responsive T cells, which activates antitumor immunity and thus prolongs the survival of patients with malignant glioma. A Japanese phase II study (Study GD01) was conducted in patients with glioblastoma who had residual or recurrent tumors after radiotherapy with concomitant temozolomide. In Study GD01, however, stable disease continued for an extended period in some patients with glioblastoma. Hence, Delytact Injection is expected to be effective to a certain level. In line with this, Delytact Injection has been approved as an option for the treatment of malignant glioma, with one of the 3 approval conditions including conducting a use-results comparison survey and resubmission of the marketing authorization application within the granted time period of 7 years, under the conditional and time-limited approval scheme described in Article 23–26 of Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices.
The association between mortality and door-to-antibiotic time: a systematic review and meta-analysis
Authors: Huang Jiao , Yang Jiang-tao , Liu Jing-chen 
Published: March 2023

Abstract

Purpose
Previous studies evaluating the impact of antibiotic timing on mortality in sepsis have shown conflicting results. We performed a meta-analysis to evaluate the association between door-to-antibiotic time (each hour of delay) and mortality in sepsis.

Methods
We searched PubMed and Embase through 10 November 2022 to identity cohort studies that evaluated the adjusted association between door-to-antibiotic time (each hour of delay) and mortality in adult patients with sepsis. The primary outcome was mortality. Analysis was based on inverse-variance weighting using a fixed-effects model. The variances were derived from the logarithms of the reported confidence intervals (CIs) for associations. We estimated the odds ratio, 95% CI, and number needed to treat for the pooled data.

Results
Fifteen cohort studies involving 106 845 patients were included in the meta-analysis. Door-to-antibiotic time (each hour of delay) was associated with increased risk of mortality (odds ratio: 1.07; 95% CI: 1.06–1.08; P &lt; 0.0001; number needed to treat = 91), with high heterogeneity (I2 = 82.2%). The association was robust in sensitivity analyses and consistent in subgroup analyses. No publication bias was found.

Conclusion
In adult patients with sepsis, each hour of delay in antibiotic administration is associated with increased odds of mortality.
Key messages What is already known on this topic Sepsis is a common and lethal syndrome that affects millions of people worldwide. The updated 2018 Surviving Sepsis Campaign guidelines recommended initiating empirical broad-spectrum antibiotic coverage within 1 hour of identification of sepsis and septic shock. Delay in antibiotic administration may increase the risk of mortality in patients with sepsis. What this study adds This meta-analysis evaluates and quantifies the association between door-to-antibiotic time (each hour of delay) and mortality in patients with sepsis. Each hour of delay in antibiotic administration is associated with increased odds of mortality in sepsis. The number needed to treat (NNT) with delayed antibiotic administration for one additional death was 91. How this study might affect research, practice, or policy: More efforts should be made to speed up the diagnosis of sepsis or sepsis shock.
Dopamine multivalent-modified polyaspartic acid for MRI-guided near-infrared photothermal therapy
Authors: Du Liang , Chen Wei , Zhong Jie , Yan Shuang , Yang Chenwu , Pu Yu , Zhu Jiang , Chen Tianwu , Zhang Xiaoming , Wu Changqiang 
Published: March 2023

AbstractNanophotothermal agents that provide efficient and precise treatment at tumor sites are attracting increasing attention in biomedicine. In particular, the method combination of nanophotothermal agents and magnetic resonance imaging (MRI) shows great promise for biomedical therapeutic applications. Herein, a simple nanophotothermal agent with dopamine multivalent-modified polyaspartic acid chelated superparamagnetic iron oxide (SPIO) and ferric ion (SPIO@PAsp-DAFe/PEG) was developed for MRI-guided near-infrared photothermal therapy (PTT). SPIO@PAsp-DAFe/PEG was random SPIO nanocluster with good water solubility, had a diameter of 57.8 ± 7.8 nm in dynamic light scattering, negatively charged surface (zeta potential = −11 mV), exhibited good stability and outstanding photothermal conversion efficiency (35.4%) and produced superior magnetic resonance enhanced imaging. In the experiment with tumor-bearing mice, the MRI not only monitored the accumulation of SPIO@PAsp-DAFe/PEG nanocomposites enhanced by near-infrared irradiation after intravenous administration but also determined the appropriate time window for PTT. With the use of MRI-guided near-infrared therapy, the SPIO@PAsp-DAFe/PEG nanocomposites provided excellent therapeutic effects, confirming their great potential as effective MRI/PTT therapeutic agents.
Upside down and the game of C allocation
Authors: Rezaie Negar , D’Andrea Ettore , Scartazza Andrea , Gričar Jožica , Prislan Peter , Calfapietra Carlo , Battistelli Alberto , Moscatello Stefano , Proietti Simona , Matteucci Giorgio 
Published: March 2023

Abstract
Non-structural carbohydrates (NSCs) represent the primary carbon (C) reserves and play a crucial role in plant functioning and resilience. Indeed, these compounds are involved in the regulation between C supply and demand, and in the maintenance of hydraulic efficiency. Non-structural carbohydrates are stored in parenchyma of woody organs, which is recognized as a proxy for reserve storage capacity of tree. Notwithstanding the importance of NSCs for tree physiology, their long-term regulation and trade-offs against growth were not deeply investigated. This work evaluated the long-term dynamics of mature tree reserves in stem and root, proxied by parenchyma features and focusing on the trade-off and interplay between the resources allocation in radial growth and reserves in stem and coarse root. In a Mediterranean beech forest, NSCs content, stem and root wood anatomy analysis and eddy covariance data were combined. The parenchyma fraction (RAP) of beech root and stem was different, due to differences in axial parenchyma (AP) and narrow ray parenchyma (nRP) fractions. However, these parenchyma components and radial growth showed synchronous inter-annual dynamics between the two organs. In beech stem, positive correlations were found among soluble sugars content and nRP and among starch content and the AP. Positive correlations were found among Net Ecosystem Exchange (NEE) and AP of both organs. In contrast, NEE was negatively correlated to radial growth of root and stem. Our results suggest a different contribution of stem and roots to reserves storage and a putative partitioning in the functional roles of parenchyma components. Moreover, a long-term trade-off of C allocation between growth and reserve pool was evidenced. Indeed, in case of C source reduction, trees preferentially allocate C toward reserves pool. Conversely, in high productivity years, growth represents the major C sink.
Tobamoviruses Show Broad Host Ranges and Little Genetic Diversity Among Four Habitat Types of a Heterogeneous Ecosystem
Authors: Zamfir Adrián D. , Babalola Bisola M. , Fraile Aurora , McLeish Michael J. , García-Arenal Fernando 
Published: March 2023

Host ranges of plant viruses are poorly known, as studies have focused on pathogenic viruses in crops and adjacent wild plants. High-throughput sequencing (HTS) avoids the bias toward plant–virus interactions that result in disease. Here we study the host ranges of tobamoviruses, important pathogens of crops, using HTS analyses of an extensive sample of plant communities in four habitats of a heterogeneous ecosystem. Sequences of 17 virus operational taxonomic units (OTUs) matched references in the Tobamovirus genus, eight had narrow host ranges, and five had wide host ranges. Regardless of host range, the OTU hosts belonged to taxonomically distant families, suggesting no phylogenetic constraints in host use associated with virus adaptation, and that tobamoviruses may be host generalists. The OTUs identified as tobacco mild green mosaic virus (TMGMV), tobacco mosaic virus (TMV), pepper mild mottle virus, and Youcai mosaic virus had the largest realized host ranges that occurred across habitats and exhibited host use unrelated to the degree of human intervention. This result is at odds with assumptions that contact-transmitted viruses would be more abundant in crops than in wild plant communities and could be explained by effective seed-, contact-, or pollinator-mediated transmission or by survival in the soil. TMGMV and TMV had low genetic diversity that was not structured according to habitat or host plant taxonomy, which indicated that phenotypic plasticity allows virus genotypes to infect new hosts with no need for adaptive evolution. Our results underscore the relevance of ecological factors in host range evolution, in addition to the more often studied genetic factors. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Postoperative emergency department visits for pain after outpatient orthopaedic surgery: did rescheduling hydrocodone make a difference?
Authors: Wassef Christina , Frangenberg Alexander , Lee HaEun , Iloani Nwamaka , Bates Christopher M. , Pientka Amanda C. , Pientka William F. 
Published: March 2023

Background:
In 2014, the United States Drug Enforcement Agency rescheduled hydrocodone from schedule III to II to mitigate the opiate crisis in America. Hydrocodone has long served as common pain medication after outpatient orthopaedic surgical procedures in the United States. We hypothesize rescheduling of hydrocodone would correlate with an increase in postoperative emergency department visits for pain.

Methods:
We performed a retrospective review of all outpatient orthopaedic procedures and identified all patients who subsequently presented to our emergency department for postoperative pain for the one calendar year prior to and after the rescheduling of hydrocodone.

Results:
We identified 2984 orthopaedic procedures and 3193 emergency department visits for postoperative pain across all surgical specialties. 875 orthopaedic procedures occurred prior to hydrocodone rescheduling with 48 postoperative ED visits for pain (5.4%). 2109 procedures occurred after the rescheduling of hydrocodone with 123 ED visits for pain postoperatively (5.8%). 199 patients presented to the ED for postoperative pain, for a total of 345 visits. The median postoperative time to emergency room visit for the pre-rescheduling group was 6.5 days versus 4.0 days post-rescheduling.

Conclusions:
We identified statistically significant differences in postoperative medication and prescribed amounts. We identified no difference in the proportion of patients that went to the emergency room by timeframe relative to hydrocodone rescheduling, nor did we identify a difference between samples in terms of gender, race, insurance status, and comorbid conditions. Increased restriction on hydrocodone prescribing did not increase emergency department visits for pain after outpatient orthopaedic surgery.

Level of Evidence:
Therapeutic III.
Immune Profiling Panel Gene Set Identifies Critically Ill Patients With Low Monocyte Human Leukocyte Antigen-DR Expression: Preliminary Results From the REAnimation Low Immune Status Marker (REALISM) Study
Authors: Peronnet Estelle , Blein Sophie , Venet Fabienne , Cerrato Elisabeth , Fleurie Aurore , Llitjos Jean-François , Kreitmann Louis , Terraz Gabriel , Conti Filippo , Gossez Morgane , Rimmelé Thomas , Textoris Julien , Lukaszewicz Anne-Claire , Brengel-Pesce Karen , Monneret Guillaume ,   for the REAnimation Low Immune Status Marker (REALISM) Study Group
Published: March 2023

OBJECTIVES:
There is a crucial unmet need for biomarker-guided diagnostic and prognostic enrichment in clinical trials evaluating immune modulating therapies in critically ill patients. Low monocyte expression of human leukocyte antigen-DR (mHLA-DR), considered as a reference surrogate to identify immunosuppressed patients, has been proposed for patient stratification in immunostimulation approaches. However, its widespread use in clinic has been somewhat hampered by technical constraints inherent to flow cytometry technology. The objective of the present study was to evaluate the ability of a prototype multiplex polymerase chain reaction tool (immune profiling panel [IPP]) to identify immunosuppressed ICU patients characterized by a low mHLA-DR expression.

DESIGN:
Retrospective observational cohort study.

SETTING:
Adult ICU in a University Hospital, Lyon, France.

PATIENTS:
Critically ill patients with various etiologies enrolled in the REAnimation Low Immune Status Marker study (NCT02638779).

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
mHLA-DR and IPP data were obtained from 1,731 blood samples collected from critically ill patients with various etiologies and healthy volunteers. A partial least square regression model combining the expression levels of IPP markers was trained and used for the identification of samples from patients presenting with evidence of immunosuppression, defined here as mHLADR less than 8,000 antibodies bound per cell (AB/C). The IPP gene set had an area under the receiver operating characteristic curve (AUC) of 0.86 (95% CI 0.83–0.89) for the identification of immunosuppressed patients. In addition, when applied to the 123 patients still in the ICU at days 5–7 after admission, IPP similarly enriched the number of patients with ICU-acquired infections in the immunosuppressed group (26%), in comparison with low mHLA-DR (22%).

CONCLUSIONS:
This study reports on the potential of the IPP gene set to identify ICU patients presenting with mHLA-DR less than 8,000 AB/C. Upon further optimization and validation, this molecular tool may help in the stratification of patients that could benefit from immunostimulation in the context of personalized medicine.
Efficacy and safety of low-dose aspirin on preventing transplant renal artery stenosis: a prospective randomized controlled trial
Authors: Tian Xiangyong , Ji Bingqing , Niu Xiaoge , Duan Wenjing , Wu Xiaoqiang , Cao Guanghui , Zhang Chan , Zhao Jingge , Wang Zhiwei , Gu Yue , Cao Huixia , Qin Tao , Shao Fengmin , Yan Tianzhong 
Published: March 2023

Abstract

Background:
Transplant renal artery stenosis (TRAS) is a vascular complication after kidney transplantation associated with poor outcomes. This study aimed to analyze the efficacy and safety of low-dose aspirin for preventing TRAS.

Methods:
After kidney transplantation, patients were enrolled from January 2018 to December 2020 in Henan Provincial People's Hospital. A total of 351 enrolled recipients were randomized to an aspirin group with low-dose intake of aspirin in addition to standard treatment (n = 178), or a control group with only standard treatment (n = 173). The patients was initially diagnosed as TRAS (id-TRAS) by Doppler ultrasound, and confirmed cases were diagnosed by DSA (c-TRAS).

Results:
In the aspirin and control groups, 15.7% (28/178) and 22.0% (38/173) of the recipients developed id-TRAS, respectively, with no statistical difference. However, for c-TRAS, the difference of incidence and cumulative incidence was statistically significant. The incidence of c-TRAS was lower in the aspirin group compared with the control group (2.8% [5/178] vs. 11.6% [20/173], P = 0.001). Kaplan–Meier estimates and Cox regression model identified the cumulative incidence and hazard ratio (HR) of TRAS over time in two groups, showing that recipients treated with aspirin had a significantly lower risk of c-TRAS than those who were not treated (log-rank P = 0.001, HR = 0.23, 95% confidence interval [CI]: 0.09–0.62). The levels of platelet aggregation rate (P < 0.001), cholesterol (P = 0.028), and low-density lipoprotein cholesterol (P = 0.003) in the aspirin group were decreased compared with the control group in the third-month post-transplantation. For the incidence of adverse events, there was no statistical difference.

Conclusion:
Clinical application of low-dose aspirin after renal transplant could prevent the development of TRAS without significant adverse effects.

Trial Registration:
Clinicaltrials.gov, NCT04260828.