bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved Risk Prediction in DLBCL By Combining Clinical and PET Features with Interim PET Assessment
Authors: Hanoun Christine , Heymans Martijn , Wiegers Sanne , Bes Annelies , Duehrsen Ulrich , Huettmann Andreas , Kurch Lars , Barrington Sally F , Mikhaeel George , Lugtenburg Pieternella , Ceriani Luca , Zucca Emanuele , Gyorke Tamas , Czibor Sandor , Zwezerijnen Gerben , Boellaard Ronald , Zijlstra Josée M. , Eertink Corinne 
Published: December 2023

Background: Accurate detection of patients at high risk of treatment failure following frontline immunochemotherapy in diffuse large B-cell lymphoma (DLBCL) is of paramount importance as these patients might benefit from early treatment escalation. Recently, we introduced the IMPI prognostic model based on metabolic tumor volume (MTV), age and stage that outperformed the international prognostic index (IPI). However, radiomic features such as Dmax bulk and SUV peak as well as an early treatment response at interim PET (i-PET) as a measure of chemosensitivity using ΔSUVmax may have additional predictive value. We tested different models for risk prediction aiming at a dynamic risk tool in the era of evolving radiomic features in functional imaging.
Methods: All patients within the PETRA database with newly diagnosed DLBCL, who were treated with R-CHOP and had available clinical data, baseline PET and i-PET scans were included.
The optimal transformation of Dmax bulk, SUV peak and ΔSUV max was determined by choosing the best fitting Cox regression model with 3-year PFS as outcome, with highest R2 and lowest Akaike Information Criterion (AIC), while the cross-validated c-index was obtained as a measure for discrimination.
Subsequently, risk models were developed using clinical, baseline PET and i-PET data. The best risk model was compared to the IMPI model and our subsequent ClinicalPET model, also incorporating radiomic features (MTV, IPI, age, SUV peak and D maxbulk) by determination of risk re-classification rates and by generating kaplan-meier (KM)-curves based on 60-30-10 PFS risk groups.
Results: 1014 patients were included in the analyses. Adding i-PET reponse (ΔSUV max) to the IMPI model markedly improved outcome prediction (AIC 3177.44, c-index 0.72) and was superior to IMPI model alone (AIC 3247.09, c-index 0.68). By adding D maxbulk outcome prediction was further improved (AIC 3143.23, c-index 0.74), while SUV peak did not show significant impact on outcome (p=0.07). Compared to the IMPI and the ClinicalPET model, the new model combining baseline features (MTV, age and D maxbulk) with i-PET reponse (ΔSUV max) led to a sharper segregation of KM-curves with an improved rate of correct progression risk classification (22%; 95% confidence interval 12.1-31.1%).
Conclusions: Adding i-PET reponse to baseline clinical and PET parameters optimizes risk classification in DLBCL enabling individualized risk assessment in early phase of frontline treatment and outperforms our previous IMPI model and ClinicalPET models.
Prospective MRI and Neurocognitive Assessment of “Chemobrain” in Acute Myeloid Leukaemia: The Mineral Study
Authors: Scott Ashleigh , Lo Ada , Thompson Kate , Xia Ying , Bodimeade Harriet , Fazlollahi Amir , Curley Cameron , Lane Steven W. , Morris Kirk Lachlan , McNamara Caroline Jane , Pillai Elango S. , Weber Nicholas , Salvado Olivier , McMahon Katie L , Kennedy Glen A 
Published: December 2023

CONCLUSIONS
“Chemobrain” is commonly reported by patients treated for Acute Myeloid Leukaemia (AML), potentially attributable to chemotherapy or iron overload. We aimed to determine whether “chemobrain” could be objectively detected in AML patients.
We performed a prospective, observational, longitudinal cohort study in adults commencing chemotherapy for AML, powered to capture a potential 25% incidence of “chemobrain.” Participants underwent neurocognitive assessment (NCA) and brain magnetic resonance imaging (MRI), including iron quantitative susceptibility mapping (QSM), as a biomarker of neuro-inflammation, at three timepoints: pre-treatment (T1), end of treatment (T2), and 6 months later (T3). Longitudinal changes of minimum 1.64 SD were considered significant. The primary outcome was change in NCA score between T1-T2, with secondary correlation analyses between NCA, MRI, QSM and clinical data. This study was funded by a RBWH Foundation 2018 Diamond Care Grant.
Between January 2019 and June 2021, 20 patients were enrolled; of these, 15 and 10 remained alive/enrolled for evaluation at T2 and T3 respectively. Overall NCA scores for the cohort between T1-T2 were similar; however, four (27%) participants performed significantly worse (-1.64SD) in Language or Verbal Memory, with three returning to baseline at T3. Objective NCA score did not correlate with subjective symptoms, and quality of life and physical fatigue improved T1-T2. Cohort brain volumes were similar T1-T2; however, correlation analysis identified interesting potential associations between worse Language performance and volume loss in grey matter (GM; p=0.021) and Wernicke's area (p=0.02), and suggested increased iron susceptibility in frontal lobe (p=0.041) and possibly cortical GM (p=0.055).
Despite patient-reported symptoms, objective neurological toxicity appears uncommon in AML patients, and those with measurable impairment appear to subsequently return to baseline.
Transient Anti-Interferon Auto Antibodies in the Airway Are Associated with Recovery in Mild COVID-19
Authors: Babcock Benjamin R , Kosters Astrid , Roan Nadia R , Lee Sulggi , Ghosn Eliver E.B. 
Published: December 2023

Pre-existing blood anti-interferon autoantibodies have been associated with susceptibility to severe COVID-19. However, nothing is known about the autoantibody response in the airway mucosa of mild to severe COVID-19 patients. We profiled longitudinal samples collected from the airway and matching blood of more than 100 donors over &gt;18 months, spanning from mild COVID-19 to hospitalized patients in the ICU. We found that transiently induced anti-type I interferon autoantibodies in the nasal mucosa are a common feature and are associated with recovery from mild and moderate COVID-19.
To quantify the breadth of antibody response in blood and the airway site of infection, we developed flowBEAT, a novel flow cytometry-based assay capable of simultaneously measuring all 8 human antibody isotypes against 22 SARS-CoV-2 structural and non-structural antigens, including autoantigens. We identified the induction of nasal anti-type I interferon autoantibodies within the first two weeks of infection, waning with disease recovery. Notably, there was an inverse association between nasal and blood anti-interferon responses, while nasal anti-interferon was linked to recovery in cases of mild/moderate disease. In contrast, near-ubiquitous anti-interferon in the endotracheal aspirates of critical cases correlated with heightened airway hyper-inflammation. In both blood and mucosa, anti-interferon positively correlated with a broad anti-viral antibody response, including non-structural proteins. While nasal anti-interferon was universally transient, we identified a group of donors sustaining long-term blood anti-interferon autoantibodies who may be at risk for a more severe subsequent viral infection.
Within our longitudinal cohort, we assessed 500 infected-recovered and vaccinated samples and showed that nasal anti-SARS-CoV-2 antibodies are sustained over 18 months by repeated vaccination and boosting. We identified isotype signatures associated with disease severity and an autoantibody signature predictive of vaccine non-response. Thus, our findings emphasize the importance of continued vaccination/boosting to sustain nasal immunity and help prevent ongoing community spread. More importantly, our studies reveal predictive blood markers of protective nasal immunity and highlight a protective role for nasal anti-interferon autoantibodies in the immunopathology of COVID-19.
Stag2a or Stag2b Knockout Zebrafish Are Viable, Yet Loss of Stag2a Is Associated with Abnormal Expression of Early and Late Myeloid and Lymphoid Markers
Authors: Anderson Rebecca A , Oyarbide Usua , Corey Seth J 
Published: December 2023

Introduction:Mutations in Stromal antigen 2 ( STAG2) are frequently found in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In mice, loss of Stag2 is embryonic lethal. Conditional knockout of Stag2 in adult mice results in MDS-like hematopoietic anomalies. Zebrafish harbor two paralogues of STAG2 ( stag2a and stag2b). To date, a complete stag2-null zebrafish model organism has not been developed. Recently reported, a stag2b-/- zebrafish demonstrated downregulation in primitive erythropoiesis. However, any hematopoiesis beyond 2 days post fertilization (2 dpf) was not detailed. Furthermore, a stag2a mutant zebrafish has not been reported.
Methods and Results: Using CRISPR/Cas9 genome editing, we created a stag2a mutant anda stag2b mutant zebrafish. Both mutations result in a frame shift and premature protein truncations. Unlike the murine Stag2 -/- mutant, zebrafish stag2a -/- mutants and stag2b -/-mutants survive to adulthood, with no obvious morphological phenotypes. Detection of hemoglobin, using O-dianisidine staining, reveals anemia at 31 hours post fertilization (31 hpf) in stag2a +/- mutants (10/29), stag2a -/-mutants (10/15), stag2b +/-mutants (6/11), and stag2b -/-mutants (5/7); wildtype siblings appear unaffected. Intriguingly, at 4 dpf, stag2a maternal-zygotic mutants show increased expression levels of early and late myeloid and lymphoid markers. ( Figure 1) Work is ongoing to analyze blood cell lineages from zebrafish whole kidney marrow, the equivalent of mammalian bone marrow, in adult stag2a and adult stag2b mutants. In addition, we are characterizing the zebrafish stag2a;stag2b double mutants, which we will present.
Conclusions: In zebrafish, stag2a and stag2b contribute to proper primitive and definitive hematopoiesis. Our organismal model of Stag2 deletion in the zebrafish will yield new insight into how loss of STAG2 may lead to MDS/AML.
Real World Data Venetoclax Based Therapies in a Single Center in Latin America
Authors: Rocha Juliana Dall Agnol , Arcuri Leonardo Javier , Kojima Rodrigo Seiti , Hamerschlak Nelson , Santos Fabio P. S. , Ennes Amanda Inácio Dias , Datoguia Tarcila Santos , Nascimento Jade Zezzi , Marques Carolina Perrone , Chaves Felipe Galvão Batista , Junior Luiz Frederico Bezerra Honorato , Galvao Barbara Ferreira Cordeiro 
Published: December 2023

Introduction: Venetoclax-based therapies have changed the outcomes of acute myeloid leukemia, in combination with hypomethylating agents, low-dose cytarabine or in older patients not eligible for intensive regimens. Combinations with venetoclax with target therapy and with standard chemotherapy are being tested to improve outcomes in specific subgroups. In Latin America, the lack of clinical trials increases prescriptions not yet approved in international guidelines (off-label use). In this paper, we present data from a private reference center in Latin America for the treatment of acute myeloid leukemia and high-risk myelodysplasia.
Methods: This is a unicentric, retrospective, and non-interventional cohort study performed at Brazilian Hospital Albert Einstein. Inclusion criteria were adult patients (aged ≥18 years) diagnosed with AML between May 2019 and January 2023, who were treated with a venetoclax-based regimen. Independent variables analyzed were age, gender, prognostic risk according to ELN 2022, indication of bone marrow transplantation, and molecular and cytogenetic risk at diagnosis.
Results: Sixty-three (N= 63) patients were included, with a median age of 63.1 years old. Forty-eight patients received a combination of venetoclax and a hypomethylating agent, two were associated with low doses of cytarabine, eight were associated with target therapy (inhibitor of FLT3), and five with intensive chemotherapy. The median follow-up was 303 days, and the median use of venetoclax in those who did not suspend treatment was 352 days. The main cause of suspension was hematological toxicity. In the univariate analysis, the following onco-hematological karyotype variables, age, type of regimen combined with venetoclax, and decision for transplant did not show statistical significance.
Conclusion: Real-world data show that venetoclax-based therapies are effective in patients with AML, and their combinations have been increasingly explored.
Albumin: Globulin Reversal As a Screening Tool for Monoclonal Gammopathy (Targeted Screening) in Hospitalized Setting
Authors: Raphael Celine , Yanamandra Uday , Kumar Abhinav , Kotwal Narendra , Malhotra Pankaj , Nair Velu 
Published: December 2023

A
Introduction: There is an unmet need to discover novel targeted screening guidelines for Qmonoclonal gammopathy of undetermined clinical significance (MGUS) in the Indian scenario which can help in early detection and diagnosis. Liver function tests (LFTs) are routinely performed in hospital settings for a variety of indications, with many having albumin-globulin (A:G) ratio reversals. We have designed this study to gauge the prevalence of MGUS in individuals above the age of 50 years with A: G ratio reversal in hospitalized settings. The objectives of the study were to measure the incidence of A: G ratio reversal in total LFT samples run in the hospital for various indications and to determine whether targeted screening of unexplained A: G ratio reversal in hospitalized patients is a fruitful strategy.
Materials and Methods:
This is a single-center, prospective observational study carried out from 01 May 2022 to 30 May 2023 at tertiary care center in Western India. All the LFTs of the admitted patients over the study period to the medical wards were included in the study. Patients with A:G reversal were subjected to detailed clinical examination and investigations to rule out non-myelomatous causes for the reversal of the ratio. Samples with unexplained A:G ratio reversal and unresolving A:G reversal despite of three months of observation were subjected to Serum Protein Electrophoresis (SPEP). Data was analysed using JMP ver. 16.0.0.
Results:
A total of 5148 LFTs were screened during the study period, of which 300 (5.82%) had A:G reversal. The median age of the study population with A:G reversal was 59 years (IQR - 14.3) with a male preponderance (59%). Etiologically amongst patients with A:G reversal 54% had infection, 15% had inflammation, 13% suffer from Chronic Liver Disease and 9% have Chronic Kidney Disease. Only 9% of patients (n-27) had no evident secondary causes, and of these 11% (n-3) have an M-spike on SPEP. Of all patients with A:G reversal, 1.1% have evidence of MGUS, all being IgG Lambda variants and none having any features of smoldering or multiple myeloma based on IMWG guidelines.
Conclusion:
G reversal compounded with good clinical history and examination can be an effective tool for targeted screening of MGUS. A majority of A:G reversals in hospital settings are due to secondary causes, requiring deliberate effort for exclusion.
Transcriptome analysis reveals temporally regulated genetic networks during Drosophila border cell collective migration
Authors: Burghardt Emily , Rakijas Jessica , Tyagi Antariksh , Majumder Pralay , Olson Bradley J.S.C. , McDonald Jocelyn A. 
Published: December 2023

Abstract
Background
Collective cell migration underlies many essential processes, including sculpting organs during embryogenesis, wound healing in the adult, and metastasis of cancer cells. At mid-oogenesis, Drosophila border cells undergo collective migration. Border cells round up into a small group at the pre-migration stage, detach from the epithelium and undergo a dynamic and highly regulated migration at the mid-migration stage, and stop at the oocyte, their final destination, at the post-migration stage. While specific genes that promote cell signaling, polarization of the cluster, formation of protrusions, and cell-cell adhesion are known to regulate border cell migration, there may be additional genes that promote these distinct active phases of border cell migration. Therefore, we sought to identify genes whose expression patterns changed during border cell migration.

Results
We performed RNA-sequencing on border cells isolated at pre-, mid-, and post-migration stages. We report that 1,729 transcripts, in nine co-expression gene clusters, are temporally and differentially expressed across the three migration stages. Gene ontology analyses and constructed protein-protein interaction networks identified genes expected to function in collective migration, such as regulators of the cytoskeleton, adhesion, and tissue morphogenesis, but also uncovered a notable enrichment of genes involved in immune signaling, ribosome biogenesis, and stress responses. Finally, we validated the in vivo expression and function of a subset of identified genes in border cells.

Conclusions
Overall, our results identified differentially and temporally expressed genetic networks that may facilitate the efficient development and migration of border cells. The genes identified here represent a wealth of new candidates to investigate the molecular nature of dynamic collective cell migrations in developing tissues.
Development and validation of risk of CPS decline (RCD): a new prediction tool for worsening cognitive performance among home care clients in Canada
Authors: Guthrie Dawn M. , Williams Nicole , O’Rourke Hannah M. , Orange Joseph B. , Phillips Natalie , Pichora-Fuller M. Kathleen , Savundranayagam Marie Y. , Sutradhar Rinku 
Published: December 2023

Abstract
Background
To develop and validate a prediction tool, or nomogram, for the risk of a decline in cognitive performance based on the interRAI Cognitive Performance Scale (CPS).

Methods
Retrospective, population-based, cohort study using Canadian Resident Assessment Instrument for Home Care (RAI-HC) data, collected between 2010 and 2018. Eligible home care clients, aged 18+, with at least two assessments were selected randomly for model derivation (75%) and validation (25%). All clients had a CPS score of zero (intact) or one (borderline intact) on intake into the home care program, out of a possible score of six. All individuals had to remain as home care recipients for the six months observation window in order to be included in the analysis. The primary outcome was any degree of worsening (i.e., increase) on the CPS score within six months. Using the derivation cohort, we developed a multivariable logistic regression model to predict the risk of a deterioration in the CPS score. Model performance was assessed on the validation cohort using discrimination and calibration plots.

Results
We identified 39,292 eligible home care clients, with a median age of 79.0 years, 62.3% were female, 38.8% were married and 38.6% lived alone. On average, 30.3% experienced a worsening on the CPS score within the six-month window (i.e., a change from 0 or 1 to 2, 3, 4, 5, or 6). The final model had good discrimination (c-statistic of 0.65), with excellent calibration.

Conclusions
The model accurately predicted the risk of deterioration on the CPS score over six months among home care clients. This type of predictive model may provide useful information to support decisions for home care clinicians who use interRAI data internationally.
Comprehensive analysis of cancer of unknown primary and recommendation of a histological and immunohistochemical diagnostic strategy from China
Authors: Ren Min , Cai Xu , Jia Liqing , Bai Qianming , Zhu Xiaoli , Hu Xichun , Wang Qifeng , Luo Zhiguo , Zhou Xiaoyan 
Published: December 2023

Abstract
Background
Previous studies on cancer of unknown primary (CUP) mainly focus on treatment and prognosis in western populations and lacked clinical evaluation of different IHC markers, so this study aimed to evaluate characteristics of CUP and recommend a diagnostic strategy from a single center in China.

Methods and results
Data of 625 patients with CUP were retrospectively collected and reviewed. The patients ranged in age from 20 to 91 years, with a female-to-male ratio of 1.3:1. The predominant histological type was poor or undifferentiated adenocarcinomas (308; 49.3%). The results of Canhelp-Origin molecular testing for the identification of the tissue of origin in 262 of 369 patients (71.0%) were considered predictable (similarity score > 45), with the most common predicted primary tumor site being the breast (57, 21.8%). Unpredictable molecular results correlated with more aggressive clinical parameters and poor survival. Thee positivity rates of several targeted antibodies (GATA3, GCDFP15, TTF1, Napsin A, and PAX8), based on the clinically predicted site, were lower than those reported for the corresponding primary tumors. Nonetheless, TRPS1 and INSM1 were reliable markers of predicted breast carcinoma (75.0%) and neuroendocrine tumors (83.3%), respectively. P16 expression, as well as HPV and EBER testing contributed significantly to the diagnosis of squamous cell carcinomas. Survival analysis revealed that older ages (> 57), ≥ 3 metastatic sites, non-squamous cell carcinomas, bone/liver/lung metastases, unpredictable molecular results, and palliative treatment correlated with poor overall survival.

Conclusions
We recommend a CUP diagnostic strategy involving the use of targeted antibody panels as per histological findings that is potentially applicable in clinical practice. The markers TRPS1, INSM1, and P16 expression, as well as HPV and EBER testing are particularly valuable in this aspect. Molecular testing is also predictive of survival rates.