bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Molecular Aberrations on Discordance Among Modalities of Blast Enumeration for Risk Stratification in Myelodysplastic Neoplasms
Authors: Steiner Laurenz , Kaur Navkirandeep , Jann Johann-Christoph , Fabarius Alice , Metzgeroth Georgia , Meggendorfer Manja , Hofmann Wolf-Karsten , Jawhar Mohamad , Nowak Daniel , Streuer Alexander 
Published: December 2024

Introduction: To determine prognosis and treatment of myelodysplastic neoplasms (MDS), adequate risk stratification is a crucial element in handling MDS patients. In the Revised International Prognostic Scoring System (IPSS-R), cytogenetical data and the amount of blasts in the bone marrow (BM) smear have substantial weight. With platelet count, hemoglobin level and absolute neutrophil count as explicit parameters and defined risk categories for evaluating karyotypes, morphology-based blast enumeration remains a relatively subjective part of risk scoring. BM cytology (BM-c), BM histology (BM-h) and BM flow cytometry (BM-f) are widely used to determine the amount of blasts in MDS patients. In the cohort of MDS patients treated since 2012 in our institution, we found significant blast count discordance among these three modalities, impairing overall survival (OS) of discordant (dis) patients. Previous research has shown remarkable impact of molecular genetic aberrations on OS in MDS. Therefore, we went out to define such markers which may help to discriminate discordant diagnostic cases.
Methods/Results: We analyzed molecular genetic data of 145 MDS patients and compared the blast counts in the three modalities to determine concordant (con, n=83, 57%) and dis samples (n=62, 43%). Although there were no significant differences between these two groups regarding age, sex, hemoglobin level, platelet count and IPSS-R karyotype risk groups (all p &gt; 0.05), a pronounced difference in overall survival of low-risk MDS patients according to IPSS-R was observed (con vs. dis, median OS 72 vs. 35 months, p = 0.036). In dis cases, further analysis showed significantly more mutations regarding -7/7q deletion (9 vs. 1 cases, p = 0.04) and BCOR (6 vs. 0 cases, p = 0.03). In case of the splicing factor mutations SF3B1 (6 vs. 16 cases, p = 0.003) and U2AF1 mutations (2 vs. 7 cases, p = 0.04), significant differences in favor of concordant samples were found. Interestingly, when low-risk con and dis patients were re-stratified using IPSS-M, OS was markedly higher and differences in OS between con and dis patients vanished (72 vs. 146 months, p = 0.46).
Conclusion: Our study reveals molecular genetic features that impact the assessment of blasts by the classically used modalities BM-c, BM-h and BM-f. Samples mutated in BCOR or with -7/7q deletion showed a distinct tendency towards blast discordance, while splicing factor mutations were mostly found in con patients. As previously shown, blast discordance is relevant for OS of patients and may significantly alter therapeutic decisions, highlighting that especially in discordant cases molecular data should be considered.
Interim PET-Adapted De-Escalation Chemotherapy Regimen for Advanced Stage Classical Hodgkin Lymphoma Using Brentuximab Vedotin, Pembrolizumab, Doxorubicin, and Dacarbazine: Phase 2 Safety and Efficacy Study
Authors: Lee Hun Ju , Ravizzini Gregory , Aboismail Eslam , Wixom Jenna , Henderson Jared , Fayad Luis E. , Ahmed Sairah , Nair Ranjit , Westin Jason R. , Iyer Swaminathan P , Nze Chijioke , Al Zaki Ajlan , Vega Francisco , Wang Michael , Flowers Christopher R. , Malpica Luis 
Published: December 2024

Background:
Brentuximab vedotin (Bv), Nivolumab (N) and Pembrolizumab (P) have revolutionized the management of advanced stage classical Hodgkin Lymphoma (AS cHL). Significant improvements in both safety and efficacy have been observed with the Echelon-1 (E1) and SWOG S1826 studies. In GHSG HD18 & HD21, PET adapted strategy showed that the numbers of cycles could be reduced without affecting impact on the efficacy. Pembrolizumab followed by AVD in frontline AS cHL with minimal immune mediated adverse events (IMAE)(Allen et al Blood Advances 2023). This study incorporates pembrolizumab into the Bv+AD regimen based on the lower incidence of IMAE observed with pembrolizumab and utilizes a PET-adapted strategy to reduce chemotherapy exposure for patients with a negative interim PET scan. NCT05922904
Objectives:
This study aims to assess the safety and efficacy of PET-Adapted de-escalation of chemotherapy regimen after achieving interim PET negative.
Methods:
Study is enrolling patients with newly diagnosed stage I/II bulky mediastinal disease (≥10 cm), stage III, or stage IV cHL. Subjects will receive three cycles of BvP+AD (Bv 1.2 mg/kg capped at 100kg), pembrolizumab 400 mg [P], doxorubicin 25 mg/m2 [A], and dacarbazine 375 mg/m2 [D]). Pembrolizumab was administered in Q6 week dosing intervals (C1D1, C2D15, C4D1 and C5D15), whereas the rest of the regimen were administered Q2 weeks. Interim PET scan was performed after cycle 3. Subjects achieving PET negativity defined as Deauville scores (DS) of 1 or 2 or 3 with &gt; 90% reduction in total metabolic tumor volume (TMTV) will continue in the de-escalation arm. Subjects on the de-escalation arm will complete three additional cycles of only BvP. Subjects with positive interim PET defined as DS of 4, 5 or 3 &lt; 90% reduction of TMTV would proceed with the standard arm to complete three additional cycles of BvP+AD, for a total of six cycles.
The primary efficacy endpoint is CR rate at the end of therapy (EOT). Key secondary endpoints include safety and tolerability, ORR, duration of response (DOR), duration of complete response (DOCR), and progression-free survival (PFS). Disease response and progression are assessed using Lugano Classification Revised Staging System for malignant lymphoma, incorporating Lymphoma Response to Immunomodulatory Therapy Criteria for nodal non-Hodgkin and Hodgkin lymphomas. TMTV was calculated using Lesion cut off SUV of 4.0, by MIM software Version 7.4.
Prognostic impact of patient-reported symptoms in multiple myeloma
Authors: Abdallah Nadine , Bohra Arwa , Mammadzadeh Aytaj , Buadi Francis , Kapoor Prashant , Dispenzieri Angela , Gertz Morie , Hayman Suzanne , ElHaj Mohammed , Dingli David , Cook Joselle , Binder Moritz , Lin Yi , Kourelis Taxiarchis , Warsame Rahma , Thompson Carrie , Menser Terri , Rajkumar S. Vincent , Kumar Shaji 
Published: December 2024

Abstract
Patient-reported outcomes (PROs) are associated with treatment outcomes in multiple myeloma (MM) in the clinical trial setting. However, most PRO tools are time consuming, which hinders use in routine practice. Our institution incorporated a “Hematology Patient-Reported Symptom Screen” (HPRSS), a 3-item questionnaire for fatigue, pain, and quality of life (QOL). The main objective of this study was to evaluate the impact of these symptoms on progression-free survival (PFS) and overall survival (OS) in a real-world cohort of patients with newly diagnosed MM. This retrospective study included patients with MM diagnosed between April 2011 and December 2017, seen at Mayo Clinic (Rochester, MN), who completed the HPRSS. Patients rated their symptoms on a scale from 0 to 10. Clinically relevant symptoms were defined as scores ≥5 for pain and fatigue, and ≤5 for QOL. At diagnosis, 735 patients had scores for all domains. The median follow-up was 8.1 years. Age was associated with increased odds of fatigue and decreased QOL. Female sex and comorbidities were associated with fatigue and pain. Higher disease stage, anemia, lytic lesions, and increased plasma cell burden were associated with fatigue, pain, and decreased QOL. Clinically relevant fatigue, pain, and decreased QOL were associated with decreased PFS and OS. On multivariate analysis including age, International Staging System III, high-risk cytogenetics, and postinduction transplantation, fatigue and decreased QOL were independently associated with decreased OS. A composite HPRSS score stratified patients into 3 groups with distinct OS. Patient-reported symptoms are prognostic in patients with newly diagnosed MM. The prognostic values of fatigue and decreased QOL are independent of age, disease stage, and transplant status.
Effects of different supervised and structured physical exercise on the physical fitness trainability of children and adolescents: a meta-analysis and meta-regression
Authors: Pinho Carolina Dertzbocher Feil , Bagatini-PhD Natália Carvalho , Lisboa Salime Donida Chedid , Mello Júlio Brugnara , Cunha Giovani dos Santos 
Published: December 2024

Abstract
Background
Physical fitness has been considered an important health indicator. Several factors can impact the increase in physical fitness in children and adolescents, including chronological age, sex and BMI, in addition to training variables such as weekly frequency, session and intervention duration, and types of exercises performed. To know the importance of variables that can impact physical fitness, it is important for health professionals to identify the most efficient way of prescribing physical exercises for children and adolescents. The aim is review and meta-analyses of the effects of supervised and structured physical exercise on the physical fitness trainability of children and adolescents.

Methods
Relevant articles were searched in the PubMed, Cochrane Library, Embase and Scopus platform databases and selected based on the following criteria: children and adolescents aged between 7 and 17 years who performed any type of structured physical exercise compared to a control group without exercise and evaluating physical fitness (strength or muscular power, cardiorespiratory fitness (CRF) or speed. The results are reported in accordance with PRISMA 2020.

Results
Eighty studies were included with a total of 5769 participants. Strength exercises (ES: 1.073; 95% CI, 0.612–1.533; P < 0.001; I2: 74%), concurrent (ES: 1.054; 95% CI, 0.255–1.853; P < 0.010; I2: 72%) and sports (ES: 0.573; 95% CI, 0.015 to 1.132; P < 0.044; I2: 34%) seem to be the most effective in increasing muscular strength. Aerobic activities (ES: 0.400; 95% CI, 0.258–0.542; P < 0.001; I2: 74%), sports (ES: 0.271; 95% IC, 0.148–0.394; P < 0.001; I2: 15), or HIIT (ES: 0.668; 95% IC, 0.333–1.003; P < 0.001; I2: 29%) resulted in increased CRF (ES: 0.514; 95% IC, 0.220–1.808; P < 0.001; I2: 66%). The practice of physical exercise increased muscular power (ES: 0.241; 95% CI, 0.053–0.429; P = 0.012; I2: 0%). The practice of HIIT impacts MAS gains (ES: 0.048; 95% CI, 0.050 − 0.026; P = 0.029; I2: 44%).

Conclusion
Supervised and structured physical exercise can improve muscular strength (15–35%), CRF (5.4–8.5%), muscular power (5.6–11.8%), and MAS (5.4%) trainability in children and adolescents. Sex, BMI of the subjects and type of exercise performed (aerobic activities, exclusive to strength, HIIT or sports) should be considered when prescribing the exercise.
Acute airway inflammation following controlled biodiesel exhaust exposure in healthy subjects
Authors: Sandström Thomas , Bosson Jenny A. , Muala Ala , Kabéle Mikael , Pourazar Jamshid , Boman Christoffer , Rankin Gregory , Mudway Ian S. , Blomberg Anders , Friberg Maria 
Published: December 2024

Abstract
Background
Exposure to standard petrodiesel exhaust is linked to adverse health effects. Moreover, there is a mounting request to replace fossil-based fuels with renewable and sustainable alternatives and, therefore, rapeseed methyl ester (RME) and other biofuels have been introduced. However, recent toxicological research has indicated that biodiesel exhaust may also induce adverse health-related events.

Aim
To determine whether exposure to 100% RME biodiesel (BD100) exhaust would cause an acute airway neutrophilic recruitment in humans.

Methods
Fourteen healthy subjects underwent exposure to diluted BD100 exhaust and filtered air for 1-h, in a blinded, random fashion. Bronchoscopy with endobronchial mucosal biopsies, bronchial wash (BW) and bronchoalveolar lavage (BAL) was performed six hours after exposure. Differential cell counts and inflammatory markers were determined in the supernatant and biopsies were stained immunohistochemically.

Results
Compared with filtered air, BD100 exhaust exposure increased bronchial mucosal endothelial P-selectin adhesion molecule expression, as well as neutrophil, mast cell and CD68 + macrophage numbers. An increased influx of neutrophils and machrophages was also seen in BW.

Conclusion
Exposure to biodiesel exhaust was associated with an acute airway inflammation that appeared similar to preceding petrodiesel exposure studies. The present findings, together with the recently reported adverse cardiovascular effects after similar biodiesel exposure, indicate that biodiesel is not free of toxicity and may affect human health.
A temporary hospital intensive care unit: a preparedness concept to increase intensive care capacity
Authors: Østerås Øyvind , Almeland Stian , Landsdalen Håvard , Gjerde Stig , Sommerfelt-Pettersen Jan Knudtzon , Flaatten Hans 
Published: December 2024

Abstract
Introduction
Norway faced the possibility of the most significant strain on its intensive care capacity in decades during the COVID-19 pandemic. All Regional Health Authorities in Norway were instructed to prepare for an increase in Intensive Care Units (ICU) capacity demands. To address the surge in demand for critical care, a gymnasium within Haukeland University Hospital premises was planned to be used as a 20-bed temporary ICU. A team-based care approach was trained, where non-ICU nurses received specialized training to support ICU procedures. Maintaining up-to-date medical devices and consumables stored for preparedness through a planned rotation system that feeds into daily use are important. While shortages of medical equipment, hospital beds, and intensive care facilities may occur, personnel shortages are likely to be more significant.

Conclusions
The concept demonstrates promising potential in enhancing preparedness and maintaining critical care surge capacity during pandemics or mass casualty incidents.
Improving productivity of citramalate from CO2 by Synechocystis sp. PCC 6803 through design of experiment
Authors: Faulkner Matthew , Andrews Fraser , Scrutton Nigel 
Published: December 2024

Abstract
Background
Cyanobacteria have long been suggested as an industrial chassis for the conversion of carbon dioxide to products as part of a circular bioeconomy. The slow growth, carbon fixation rates, and limits of carbon partitioning between biomass and product in cyanobacteria must be overcome to fully realise this industrial potential. Typically, flux towards heterologous pathways is limited by the availability of core metabolites. Citramalate is produced in a single enzymatic step through the condensation of the central metabolites pyruvate and acetyl-CoA; improvements in citramalate productivity can, therefore, be used as a measure of overcoming this limitation. Furthermore, citramalate is a useful biomaterial precursor and provides a route to renewable methyl methacrylate and poly(methyl methacrylate), which is often traded as Perspex or Plexiglas.

Results
Here, we describe a phenomenon where the concerted optimisation of process parameters significantly increased citramalate production in Synechocystis sp. PCC 6803. Design of experiment principles were used to determine the optima for each parameter and the interplay between multiple parameters. This approach facilitated a ~ 23-fold increase in citramalate titre from initial unoptimised experiments. The process of scale-up from batch cultures to 0.5, 2, and 5 L photobioreactors is described. At the 2-L scale, citramalate titres from carbon dioxide reached 6.35 g/L with space–time yields of 1.59 g/L/day whilst 5-L PBRs yielded 3.96 ± 0.23 g/L with a productivity of 0.99 ± 0.06 g/L/day. We believe the decrease in productivity from 2-L to 5-L scale was likely due to the increased pathlength and shading for light delivery reducing incident light per cell. However, changes in productivity and growth characteristics are not uncommon when scaling up biotechnology processes and have numerous potential causes.

Conclusions
This work demonstrates that the use of a process parameter control regime can ameliorate precursor limitation and enhance citramalate production. Since pyruvate and/or acetyl-CoA give rise to numerous products of biotechnological interest, the workflow presented here could be employed to optimise flux towards other heterologous pathways. Understanding the factors controlling and thus increasing carbon partitioning to product will help progress cyanobacteria as part of a carbon–neutral circular bioeconomy. This is the first study using design of experiment to optimise overall carbon fixation rate and carbon partitioning to product, with the goal of improving the performance of a cyanobacterium as a host for biological carbon capture.
Impact of systemic inflammation and disease activity on the incidence of interstitial lung disease in patients with rheumatoid arthritis – a nested case-control study within the German biologics register RABBIT
Authors: Ramien Ronja , Rudi Tatjana , Alten Rieke , Krause Andreas , Schneider Matthias , Schaefer Martin , Strangfeld Anja , Meissner Yvette 
Published: December 2024

Abstract
Background
To investigate the association between the development of incident interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) and the disease activity of RA with its various components, especially C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

Methods
We analysed data from RA patients, observed in the German biologics register RABBIT between 2001 and 2021. In a nested case-control study, patients with a reported incident ILD diagnosis during follow-up were matched 1:5 to patients without ILD. Matching criteria were sex, age, RA duration, date of enrolment and observation time. Defined by a directed acyclic graph (DAG), we adjusted the conditional logistic regression models for rheumatoid factor, smoking, chronic obstructive pulmonary disease and tuberculosis/chronic viral infections to investigate the impact of disease activity/systemic inflammation. Mean and categorized values were analysed within 12 months prior to ILD and during the entire observation time. Additionally, two sensitivity analyses were performed, using validated ILD cases only and considering ILD cases with an observation time of more than 12 months.

Results
We identified 139 RA patients with incident ILD and matched them to 686 controls. In 94 cases the diagnosis could be validated, and 98 cases had a follow-up of > 12 months. The averaged DAS28 composite score (including ESR or CRP) was not associated with developing RA-ILD (odds ratios 1.16 [95% confidence interval: 0.97–1.40] and 1.06 [0.86–1.29], respectively). However, single measures of inflammation, log ESR (1.86 [1.35–2.57]) and log CRP (1.55 [1.21–1.97]), were significantly associated with an increased RA-ILD risk. A higher risk for ILD was also revealed for persistently high inflammation. Other DAS28 components showed no significant associations with RA-ILD. These results were consistent for values over the entire observation time of a patient and within 12 months prior to the ILD. Sensitivity analyses confirmed these findings.

Conclusion
Higher levels of systemic inflammation, as indicated by ESR and CRP, but not joint counts or patient’s global assessment, were significantly associated with the occurrence of incident ILD in patients with RA. As possible predictor for the development of RA-ILD, systemic inflammation should be monitored closely and independently of joint count results.
Toxicology study of a tissue anchoring paclitaxel prodrug
Authors: Chinthapatla Rukesh , Stephens Jazz Q. , Neumann-Rivera Isabel B. , Henderson Nichol M. , Nie Minhua , Haynes Hannah R. , Pierce Joshua G. , Meritet Danielle M. , Brudno Yevgeny , Oh Annie 
Published: December 2024

Abstract
Background
Local drug presentation made possible by drug-eluting depots provides benefits for a vast array of diseases, including cancer, microbial infection, and wound healing. Drug-eluting depots provide sustained drug release of therapeutics directly at disease sites with tunable kinetics, remove the need for drugs to access disease sites from circulation, and reduce the side effects associated with systemic therapy. Recently, we introduced an entirely novel approach to local drug presentation named Tissue-Reactive Anchoring Pharmaceuticals (TRAPs). TRAPs enables local drug presentation without any material carriers, capitalizing on innate tissue structures to anchor drugs at the site of administration.

Methods
In this report, we comprehensively evaluate the local and systemic toxicological profile of a paclitaxel version of TRAPs in mice by clinical observations, body weight monitoring, histopathological evaluations of injection sites and major organs, as well as blood and urine analyses.

Results
We find that intradermal administration of TRAP-paclitaxel does not induce substantial toxic effects. Localized inflammatory responses were observed at the injection sites and secondary minimal, non-specific inflammation was observed in the liver. All other organs displayed unremarkable histological findings.

Conclusions
These findings support the potential of TRAP-paclitaxel as a promising candidate for localized cancer treatment, offering high-concentration drug delivery while mitigating scarring and adverse side effects.
Silicoflagellate assemblages in the North Pacific surface sediments: an application of the modern analog method to reconstruct the glacial sea surface temperature in the Japan Sea
Authors: Okazaki Yusuke , Onodera Jonaotaro , Tanizaki Kyohei , Nishizono Fumiaki , Egashira Kazuki , Tomokawa Asuka , Sagawa Takuya , Horikawa Keiji , Ikehara Ken 
Published: December 2024

AbstractRecent silicoflagellate distributions have been examined in 195 surface sediment samples from the North Pacific to establish the silicoflagellate assemblage dataset from surface sediments across the North Pacific for paleo sea surface temperature (SST) reconstruction. The relative abundance data of all seven silicoflagellate taxa identified in this study were used for the modern analog method to reconstruct past SST. The SST reconstruction based on the silicoflagellate modern analog technique was applied to the two sediment cores from the Japan Sea. With the development of ice sheets, the Japan Sea experienced a low salinity isolation event during the Last Glacial Maximum (LGM: 19 ka–26.5 ka), which hampers the SST reconstruction employing geochemical proxies such as alkenone and Mg/Ca thermometry. The reconstructed glacial SST between 25 and 15 ka was ~ 5 °C in the northern and southern Japan Sea, indicating significant southward migration of the glacial subpolar front. The timings of the deglacial SST rises were ~ 14 ka at the south core site and ~ 10 ka at the north core site, indicating a latitudinal lag. This lag likely reflects a gradual increase in the fluxes of the Tsushima Warm Current from the East China Sea through the Tsushima Strait. Compilation of the silicoflagellate assemblages in the North Pacific surface sediments used for the modern analog technique to reconstruct past sea surface temperature (SST), revealing the Japan Sea SST during the last glacial maximum ~20 ka ago.