bluuebunny/crossref_metadata_2025_split huggingface dataset:
Landscape of HER2-low metastatic breast cancer (MBC): results from the Austrian AGMT_MBC-Registry
Authors: Gampenrieder Simon Peter , Rinnerthaler Gabriel , Tinchon Christoph , Petzer Andreas , Balic Marija , Heibl Sonja , Schmitt Clemens , Zabernigg August Felix , Egle Daniel , Sandholzer Margit , Singer Christian Fridolin , Roitner Florian , Hager Christopher , Andel Johannes , Hubalek Michael , Knauer Michael , Greil Richard 
Published: December 2021

AbstractBackgroundAbout 50% of all primary breast cancers show a low-level expression of HER2 (HER2-low), defined as immunohistochemically 1+ or 2+ and lack of HER2 gene amplification measured by in situ hybridization. This low HER2 expression is a promising new target for antibody–drug conjugates (ADCs) currently under investigation. Until now, little is known about the frequency and the prognostic value of low HER2-expression in metastatic breast cancer (MBC).Patients and methodsThe MBC-Registry of the Austrian Study Group of Medical Tumor Therapy (AGMT) is a multicenter nationwide ongoing registry for MBC patients in Austria. Unadjusted, univariate survival probabilities of progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan–Meier method and compared by the log-rank test. Multivariable adjusted hazard ratios were estimated by Cox regression models. In this analysis, only patients with known HER2 status and available survival data were included.ResultsAs of 11/15/2020, 1,973 patients were included in the AGMT-MBC-Registry. Out of 1,729 evaluable patients, 351 (20.3%) were HER2-positive, 608 (35.2%) were HER2-low and 770 (44.5%) were completely HER2-negative (HER2-0). Low HER2-expression was markedly more frequent in the hormone-receptor(HR)+ subgroup compared to the triple-negative subgroup (40% vs. 23%). In multivariable analysis, low HER2 expression did not significantly influence OS neither in the HR+ (HR 0.89; 95% CI 0.74–1.05;P = 0.171) nor in the triple-negative subgroup (HR 0.92; 95% CI 0.68–1.25;P = 0.585), when compared to completely HER2-negative disease. Similar results were observed when HER2 IHC 2+ patients were compared to IHC 1+ or 0 patients.ConclusionLow-HER2 expression did not have any impact on prognosis of metastatic breast cancer in this real-world population.
Quantitative assessment of the immune microenvironment in African American Triple Negative Breast Cancer: a case–control study
Authors: Yaghoobi Vesal , Moutafi Myrto , Aung Thazin Nwe , Pelekanou Vasiliki , Yaghoubi Sanam , Blenman Kim , Ibrahim Eiman , Vathiotis Ioannis A. , Shafi Saba , Sharma Anup , O’Meara Tess , Fernandez Aileen I. , Pusztai Lajos , Rimm David L. 
Published: December 2021

Abstract
Purpose
Triple negative breast cancer (TNBC) is more common in African American (AA) than Non-AA (NAA) population. We hypothesize that tumor microenvironment (TME) contributes to this disparity. Here, we use multiplex quantitative immunofluorescence to characterize the expression of immunologic biomarkers in the TME in both populations.

Patients and methods
TNBC tumor resection specimen tissues from a 100-patient case: control cohort including 49 AA and 51 NAA were collected. TME markers including CD45, CD14, CD68, CD206, CD4, CD8, CD20, CD3, Ki67, GzB, Thy1, FAP, aSMA, CD34, Col4, VWF and PD-L1 we quantitatively assessed in every field of view. Mean expression levels were compared between cases and controls.

Results
Although no significant differences were detected in individual lymphoid and myeloid markers, we found that infiltration with CD45+ immune cells (p = 0.0102) was higher in TNBC in AA population. AA TNBC tumors also had significantly higher level of lymphocytic infiltration defined as CD45+ CD14− cells (p = 0.0081). CD3+ T-cells in AA tumors expressed significantly higher levels of Ki67 (0.0066) compared to NAAs, indicating that a higher percentage of AA tumors contained activated T-cells. All other biomarkers showed no significant differences between the AA and NAA group.

Conclusions
While the TME in TNBC is rich in immune cells in both racial groups, there is a numerical increase in lymphoid infiltration in AA compared to NAA TNBC. Significantly, higher activated T cells seen in AA patients raises the possibility that there may be a subset of AA patients with improved response to immunotherapy.
Benchmarking UMI-based single-cell RNA-seq preprocessing workflows
Authors: You Yue , Tian Luyi , Su Shian , Dong Xueyi , Jabbari Jafar S. , Hickey Peter F. , Ritchie Matthew E. 
Published: December 2021

Abstract
Background
Single-cell RNA-sequencing (scRNA-seq) technologies and associated analysis methods have rapidly developed in recent years. This includes preprocessing methods, which assign sequencing reads to genes to create count matrices for downstream analysis. While several packaged preprocessing workflows have been developed to provide users with convenient tools for handling this process, how they compare to one another and how they influence downstream analysis have not been well studied.

Results
Here, we systematically benchmark the performance of 10 end-to-end preprocessing workflows (Cell Ranger, Optimus, salmon alevin, alevin-fry, kallisto bustools, dropSeqPipe, scPipe, zUMIs, celseq2, and scruff) using datasets yielding different biological complexity levels generated by CEL-Seq2 and 10x Chromium platforms. We compare these workflows in terms of their quantification properties directly and their impact on normalization and clustering by evaluating the performance of different method combinations. While the scRNA-seq preprocessing workflows compared vary in their detection and quantification of genes across datasets, after downstream analysis with performant normalization and clustering methods, almost all combinations produce clustering results that agree well with the known cell type labels that provided the ground truth in our analysis.

Conclusions
In summary, the choice of preprocessing method was found to be less important than other steps in the scRNA-seq analysis process. Our study comprehensively compares common scRNA-seq preprocessing workflows and summarizes their characteristics to guide workflow users.
Flimma: a federated and privacy-aware tool for differential gene expression analysis
Authors: Zolotareva Olga , Nasirigerdeh Reza , Matschinske Julian , Torkzadehmahani Reihaneh , Bakhtiari Mohammad , Frisch Tobias , Späth Julian , Blumenthal David B. , Abbasinejad Amir , Tieri Paolo , Kaissis Georgios , Rückert Daniel , Wenke Nina K. , List Markus , Baumbach Jan 
Published: December 2021

AbstractAggregating transcriptomics data across hospitals can increase sensitivity and robustness of differential expression analyses, yielding deeper clinical insights. As data exchange is often restricted by privacy legislation, meta-analyses are frequently employed to pool local results. However, the accuracy might drop if class labels are inhomogeneously distributed among cohorts. Flimma (https://exbio.wzw.tum.de/flimma/) addresses this issue by implementing the state-of-the-art workflow limma voom in a federated manner, i.e., patient data never leaves its source site. Flimma results are identical to those generated by limma voom on aggregated datasets even in imbalanced scenarios where meta-analysis approaches fail.
Pharmacist-guided pre-emptive pharmacogenetic testing in antidepressant therapy (PrePGx): study protocol for an open-label, randomized controlled trial
Authors: Stäuble Céline K. , Lampert Markus L. , Allemann Samuel , Hatzinger Martin , Hersberger Kurt E. , Meyer zu Schwabedissen Henriette E. , Imboden Christian , Mikoteit Thorsten 
Published: December 2021

AbstractBackgroundIt is known that only 50% of patients diagnosed with major depressive disorders (MDD) respond to the first-line antidepressant treatment. Accordingly, there is a need to improve response rates to reduce healthcare costs and patient suffering. One approach to increase rates of treatment response might be the integration of pharmacogenetic (PGx) testing to stratify antidepressant drug selection. The goal of PGx assessments is to identify patients who have an increased risk to experience adverse drug reactions or non-response to specific drugs. Especially for antidepressants, there is compiling evidence on PGx influencing drug exposure as well as response.MethodsThis study is an open-label, randomized controlled trial conducted in two study centers in Switzerland: (1) the Psychiatric Clinic of Solothurn and (2) the Private Clinic Wyss in Münchenbuchsee. Adult inpatients diagnosed with a unipolar moderate or severe depressive episode are recruited at clinic admission and are included in the study. If the adjustment to a new antidepressant pharmacotherapy is necessary, the participants are randomized to either Arm A (intervention group) or Arm B (control group). If no new antidepressant pharmacotherapy is introduced the participants will be followed up in an observational arm. The intervention is the service of pharmacist-guided pre-emptive PGx testing to support clinical decision making on antidepressant selection and dosing. As a comparison, in the control group, the antidepressant pharmacotherapy is selected by the treating physician according to current treatment guidelines (standard of care) without the knowledge of PGx test results and support of clinical pharmacists. The primary outcome of this study compares the response rates under antidepressant treatment after 4 weeks between intervention and control arm.DiscussionThe findings from this clinical trial are expected to have a direct impact on inter-professional collaborations for the handling and use of PGx data in psychiatric practice.Trial registrationClinicalTrials.govNCT04507555. Registered on August 11, 2020. Swiss National Clinical Trials PortalSNCTP000004015. Registered August 18, 2020.
Emotional Regulation in Teens and Improvement of Constructive Skills (EmoTIConS): study protocol for a randomized controlled trial
Authors: Pedrini Laura , Rossi Roberta , Magni Laura Rosa , Lanfredi Mariangela , Meloni Serena , Ferrari Clarissa , Macis Ambra , Lopizzo Nicola , Zonca Valentina , Cattaneo Annamaria 
Published: December 2021

Abstract
Background
Emotional dysregulation (ED) constitutes a relevant factor involved in the onset and maintenance of many mental disorders. Targeting ED during adolescence could be a determinant both to identify high-risk individuals and to promote preventive interventions. This study will aim to evaluate the impact of a brief Dialectical Behavioral Therapy (DBT)-based intervention for adolescent students by measuring changes in emotional regulation skills and impulsive behaviors. Moreover, alterations in biological features related to stress response and inflammation will be assessed as potential biological variables associated with ED.

Methods
This is a randomized trial. A total of 20 classes of adolescent students will be recruited among high schools in Brescia, a city in northern Italy. They will be randomized to the psychoeducational intervention (experimental group) or to a control condition (control group). The intervention will be based on DBT Skills Training for Emotional Problem Solving for Adolescents, and will consist of four monthly, 2-h sessions (for a total of 8 h) scheduled during regular school time. Participants will be assessed at baseline, post-intervention, and at 3 and 6 months of follow-up. The primary outcome measures will be represented by changes in the use of emotional regulation skills and by changes in the frequency of impulsive behaviors. Salivary samples will be collected at baseline and post-intervention to explore possible biological features underlying ED.

Discussion
Data from the present project will offer the opportunity to better understand the complex phenomenon of ED. Repeated assessment will cover several domains (emotional, behavioral, social, biological) as potential factors associated with ED. Moreover, it will be possible to establish the effect of the proposed intervention, thus helping to improve knowledge on the impact of school-based universal preventive programs. Finally, the current trial will propose an integrated screening and intervention-based model. Ultimately, this could reduce barriers to youths’ mental health care by fostering collaboration between schools and mental health services.

Trial registration
ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04349709?cond=emotional+dysregulation&cntry=IT&draw=2&rank=1. Registered on April 16, 2020.
The ability of a submaximal cycle ergometer test to detect longitudinal changes in VO2max
Authors: Björkman Frida , Ekblom Örjan , Ekblom-Bak Elin , Bohman Tony 
Published: December 2021

AbstractBackgroundThe purpose of the present study was to examine the ability of a submaximal cycling test to detect longitudinal changes in maximal oxygen uptake (VO2max) and examine the conformity between changes in measured and estimated VO2max over a time span of 5–8 years.MethodsA total of 35 participants (21 men and 14 women), aged 29 to 63 years, performed the Ekblom-Bak (EB) submaximal cycle test for estimation of VO2max and a maximal treadmill running test for direct measurement of VO2max. The baseline tests were conducted between 2009 and 2012, and the follow-up tests were completed 5 to 8 years later. Pearson’s coefficient of correlation (r) and paired samplet-test were used to analyse the association between change in measured and estimated VO2max. Random and systematic errors between the measured and estimated VO2max were evaluated using Bland-Altman plots. Repeated measures ANOVA were used to test differences between changes over time.ResultsThere was no significant change in mean measured VO2max between baseline and follow-up (p= 0.91), however large individual variations were noted (− 0.78 to 0.61 L/min). The correlation between individual change in measured and estimated VO2max wasr= 0.75 (p< 0.05), and the unstandardised B-coefficient from linear regression modelling was 0.88 (95% CI 0.61 to 1.15), i.e., for each litre of change in estimated VO2max, the measured value had changed 0.88 L. The correlation between baseline and follow-up errors (the difference between estimated-measured VO2max at each occasion) wasr= 0.84 (p< 0.05). With regard to the testing procedure, repeated measures ANOVA revealed that there was no significant difference between the group who exercised at the same work rates at baseline and follow-up (n = 25), and those who required a change in work rate (n = 10).ConclusionsThe EB test detected a change in VO2max with reasonably good precision over a time span of 5–8 years. Further studies are needed to evaluate if the test can be used in clinical populations and in subjects with different medications.
Lipid A-Ara4N as an alternate pathway for (colistin) resistance in Klebsiella pneumonia isolates in Pakistan
Authors: Masood Kiran Iqbal , Umar Seema , Hasan Zahra , Farooqi Joveria , Razzak Safina Abdul , Jabeen Nazish , Rao Jason , Shakoor Sadia , Hasan Rumina 
Published: December 2021

Abstract
Objectives
This study aimed to explore mechanism of colistin resistance amongst Klebsiella pneumoniae isolates through plasmid mediated mcr-1 gene in Pakistan. Carbapenem and Colistin resistant K. pneumoniae isolates (n  = 34) stored at − 80 °C as part of the Aga Khan University Clinical Laboratory strain bank were randomly selected and subjected to mcr-1 gene PCR. To investigate mechanisms of resistance, other than plasmid mediated mcr-1 gene, whole genome sequencing was performed on 8 clinical isolates, including 6 with colistin resistance (MIC  >  4 μg/ml) and 2 with intermediate resistance to colistin (MIC  >  2 μg/ml).

Results
RT-PCR conducted revealed absence of mcr-1 gene in all isolates tested. Whole genome sequencing results revealed modifications in Lipid A-Ara4N pathway. Modifications in Lipid A-Ara4N pathway were detected in ArnA_ DH/FT, UgdH, ArnC and ArnT genes. Mutation in ArnA_ DH/FT gene were detected in S3, S5, S6 and S7 isolates. UgdH gene modifications were found in all isolates except S3, mutations in ArnC were present in all except S1, S2 and S8 and ArnT were detected in all except S4 and S7. In the absence of known mutations linked with colistin resistance, lipid pathway modifications may possibly explain the phenotype resistance to colistin, but this needs further exploration.
Detection of the sentinel lymph node with hybrid tracer (ICG-[99mTc]Tc-albumin nanocolloid) in intermediate- and high-risk endometrial cancer: a feasibility study
Authors: Sánchez-Izquierdo Nuria , Vidal-Sicart Sergi , Campos Francisco , Torné Aureli , Angeles Martina Aida , Migliorelli Federico , Munmany Meritxell , Saco Adela , Diaz-Feijoo Berta , Glickman Ariel , Ordi Jaume , Perissinotti Andrés , del Pino Marta , Paredes Pilar 
Published: December 2021

AbstractPurposeIndocyanine green (ICG) is frequently used for the detection of the sentinel lymph node (SLN) in gynecology, but it carries the loss of the presurgical SLN mapping provided by [99mTc]-based colloids. Hybrid tracers such as ICG-[99mTc]Tc-albumin nanocolloid combine the benefits of both components. The aim of this study was to evaluate the feasibility and applicability of this hybrid tracer injected by transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR) approach in the detection of SLNs in patients with intermediate- and high-risk EC.MethodsFifty-two patients with intermediate- and high-risk EC underwent SLN biopsy after injection of a hybrid tracer using the TUMIR approach, followed by pelvic and paraaortic lymphadenectomy. SLNs were detected preoperatively by lymphoscintigraphic study and intraoperatively by gamma probe and near-infrared (NIR) optical laparoscopic camera.ResultsPreoperative lymphatic drainage was obtained in 69% and intraoperative detection in 71.4% of patients. A total of 146 SLNs (4.17 SLNs/patient) were biopsied. Pelvic bilateral detection was observed in 57% of the women and paraaortic drainage in 34% of the patients. The radioactive component allowed the detection of SLN in 97.1% of the patients, while the fluorescent component detected 80%. In more than 17% of the patients with intraoperative detection, SLNs were detected only by the radioactive signal. Lymph node metastasis was identified in 14.3% of patients submitted to SLNB. The sensitivity and negative predictive value for metastatic involvement were 100%.ConclusionTUMIR injection of a hybrid tracer in patients with intermediate- and high-risk EC combines the benefits of the radiotracer and the fluorescence methods with a single tracer. The method increases the paraaortic detection rate and allows a potential increase in SLN detection. Notwithstanding, based on our findings, the radioactive component of the hybrid tracer cannot be obviated.
Dynamic scene deblurring and image de-raining based on generative adversarial networks and transfer learning for Internet of vehicle
Authors: Wei Bingcai , Zhang Liye , Wang Kangtao , Kong Qun , Wang Zhuang 
Published: December 2021

AbstractExtracting traffic information from images plays an increasingly significant role in Internet of vehicle. However, due to the high-speed movement and bumps of the vehicle, the image will be blurred during image acquisition. In addition, in rainy days, as a result of the rain attached to the lens, the target will be blocked by rain, and the image will be distorted. These problems have caused great obstacles for extracting key information from transportation images, which will affect the real-time judgment of vehicle control system on road conditions, and further cause decision-making errors of the system and even have a bearing on traffic accidents. In this paper, we propose a motion-blurred restoration and rain removal algorithm for IoV based on generative adversarial network and transfer learning. Dynamic scene deblurring and image de-raining are both among the challenging classical research directions in low-level vision tasks. For both tasks, firstly, instead of using ReLU in a conventional residual block, we designed a residual block containing three 256-channel convolutional layers, and we used the Leaky-ReLU activation function. Secondly, we used generative adversarial networks for the image deblurring task with our Resblocks, as well as the image de-raining task. Thirdly, experimental results on the synthetic blur dataset GOPRO and the real blur dataset RealBlur confirm the effectiveness of our model for image deblurring. Finally, as an image de-raining task based on transfer learning, we can fine-tune the pre-trained model with less training data and show good results on several datasets used for image rain removal.
Net zero 2050 as an EU priroty: modeling a system for efficient investments in eco innovation for climate change mitigation
Authors: Jesic Jelena , Okanovic Andrea , Panic Andrea Andrejevic 
Published: December 2021

Abstract
Background
The study background is based on the fact that The Recovery Plan for Europe envisages investing 30% of the huge budget in climate change, with the goal of zero gas emission by 2050. This ambitious plan will require (for now indefinitely) investments in research and innovation. The study’s main objective is to check and analyze the existing and propose a new model of effective investments in eco-innovation. This will contribute to effective long-term investment policy, climate change impact, and mitigation of consequences.

Methods
The basic methodological tools for solving the problems discussed in this study were correlation analysis, regression analysis, and paired sample t-test. All calculations were performed in the SPSS 20 statistical software. Time series data of the selected indicators were obtained from the European Innovation Scoreboard 2020. The database used to collect the data for the EU member countries and selected third countries for the analysis is the European Innovation Scoreboard 2020. To avoid sample selection bias, the authors considered all of the available data for all the member countries and selected third countries in the European Innovation Scoreboard 2020 for the 2012 to 2019 period.

Results
The study results show the path developing countries should follow in directing their inevitable and increasing eco-innovation investments, taking into account the arguments of structural differences in financing Research and Development (R&D). The authors’ findings support the thesis that investments in R&D is low in developing countries, while in developed EU countries, there are more investments in R&D from the business sector for the 2012–2019 period.

Conclusions
Study conclusions are summarized as a proposal of the appropriate R&D financing model approach to developing countries with a greater share of eco-innovation and self-sustainable R&D financing for climate preserving products. This study is important as it provides new evidence on financing R&D investments in innovation leader countries and emerging innovator countries according to Summary Innovation Index.