bluuebunny/crossref_metadata_2025_split huggingface dataset:
Objective Analysis and Clinical Significance of the Spatial Tumor-Infiltrating Lymphocyte Patterns in Non–Small Cell Lung Cancer
Authors: Lopez de Rodas Miguel , Wang Yvonne , Peng Gang , Gu Jianlei , Mino-Kenudson Mari , Riess Jonathan W. , Velcheti Vamsidhar , Hellmann Matthew , Gainor Justin F. , Zhao Hongyu , Schalper Kurt A. 
Published: December 2023

Abstract

Purpose:
The spatial arrangement of lymphocytes in the tumor bed (e.g., immune infiltrated, immune excluded, immune desert) is expected to reflect distinct immune evasion mechanisms and to associate with immunotherapy outcomes. However, data supporting these associations are scant and limited by the lack of a clear definition for lymphocyte infiltration patterns and the subjective nature of pathology-based approaches.

Experimental Design:
We used multiplexed immunofluorescence to study major tumor-infiltrating lymphocyte (TIL) subsets with single-cell resolution in baseline whole-tissue section samples from NSCLC patients treated with immune checkpoint inhibitors (ICI). The spatial TIL patterns were analyzed using a qualitative pathologist-based approach, and an objective analysis of TIL density ratios in tumor/stromal tissues. The association of spatial patterns with outcomes was studied for different TIL markers.

Results:
The analysis of CD8+ TIL patterns using qualitative assessment identified prominent limitations including the presence of a broad spectrum of phenotypes within most tumors and limited association with outcomes. The utilization of an objective method to classify NSCLCs showed the existence of at least three subgroups with partial overlap with those defined using visual patterns. Using this strategy, a subset of cases with “immune excluded-like” tumors showed prominently worse outcomes, suggesting reduced sensitivity to ICI; however, these results need to be validated. The analysis for other TIL subsets showed different results, underscoring the relevance of the marker selected for spatial TIL pattern evaluation and opportunities for market integration.

Conclusions:
Our results identified major challenges associated with the qualitative spatial TIL pattern evaluation. We devised a novel objective strategy to overcome some of these limitations that has strong biomarker potential.
Whole-Blood Transcriptome Unveils Altered Immune Response in Acute Myocardial Infarction Patients With Aortic Valve Sclerosis
Authors: Piacentini Luca , Myasoedova Veronika A. , Chiesa Mattia , Vavassori Chiara , Moschetta Donato , Valerio Vincenza , Giovanetti Gloria , Massaiu Ilaria , Cosentino Nicola , Marenzi Giancarlo , Poggio Paolo , Colombo Gualtiero I. 
Published: December 2023

BACKGROUND:
Aortic valve sclerosis (AVSc) presents similar pathogenetic mechanisms to coronary artery disease and is associated with short- and long-term mortality in patients with coronary artery disease. Evidence of AVSc-specific pathophysiological traits in acute myocardial infarction (AMI) is currently lacking. Thus, we aimed to identify a blood-based transcriptional signature that could differentiate AVSc from no-AVSc patients during AMI.

METHODS:
Whole-blood transcriptome of AVSc (n=44) and no-AVSc (n=66) patients with AMI was assessed by RNA sequencing on hospital admission. Feature selection, differential expression, and enrichment analyses were performed to identify gene expression patterns discriminating AVSc from no-AVSc and infer functional associations. Multivariable Cox regression analysis was used to estimate the hazard ratios of cardiovascular events in AVSc versus no-AVSc patients.

RESULTS:
This cross-sectional study identified a panel of 100 informative genes capable of distinguishing AVSc from no-AVSc patients with 94% accuracy. Further analysis revealed significant mean differences in 143 genes, of which 30 genes withstood correction for age and previous AMI or coronary interventions. Functional inference unveiled a significant association between AVSc and key biological processes, including acute inflammatory responses, type I IFN (interferon) response, platelet activation, and hemostasis. Notably, patients with AMI with AVSc exhibited a significantly higher incidence of adverse cardiovascular events during a 10-year follow-up period, with a full adjusted hazard ratio of 2.4 (95% CI, 1.3–4.5).

CONCLUSIONS:
Our findings shed light on the molecular mechanisms underlying AVSc and provide potential prognostic insights for patients with AMI with AVSc. During AMI, patients with AVSc showed increased type I IFN (interferon) response and earlier adverse cardiovascular outcomes. Novel pharmacological therapies aiming at limiting type I IFN response during or immediately after AMI might improve poor cardiovascular outcomes of patients with AMI with AVSc.
MicroRNA-1 Deficiency Is a Primary Etiological Factor Disrupting Cardiac Contractility and Electrophysiological Homeostasis
Authors: Yang Dandan , Wan Xiaoping , Schwieterman Neill , Cavus Omer , Kacira Ege , Xu Xianyao , Laurita Kenneth R. , Wold Loren E. , Hund Thomas J. , Mohler Peter J. , Deschênes Isabelle , Fu Ji-Dong 
Published: December 2023

BACKGROUND:

MicroRNA-1 (miR1), encoded by the genes
miR1-1
and
miR1-2
, is the most abundant microRNA in the heart and plays a critical role in heart development and physiology. Dysregulation of miR1 has been associated with various heart diseases, where a significant reduction (>75%) in miR1 expression has been observed in patient hearts with atrial fibrillation or acute myocardial infarction. However, it remains uncertain whether miR1-deficiency acts as a primary etiological factor of cardiac remodeling.

METHODS:

miR1-1
or
miR1-2
knockout mice were crossbred to produce 75%-miR1-knockdown (75%KD;

miR1-1
+/−
:miR1-2
−/−

or

miR1-1
−/−
:miR1-2
+/−

) mice. Cardiac pathology of 75%KD cardiomyocytes/hearts was investigated by ECG, patch clamping, optical mapping, transcriptomic, and proteomic assays.

RESULTS:

In adult 75%KD hearts, the overall miR1 expression was reduced to ≈25% of the normal wild-type level. These adult 75%KD hearts displayed decreased ejection fraction and fractional shortening, prolonged QRS and QT intervals, and high susceptibility to arrhythmias. Adult 75%KD cardiomyocytes exhibited prolonged action potentials with impaired repolarization and excitation-contraction coupling. Comparatively, 75%KD cardiomyocytes showcased reduced Na
+
current and transient outward potassium current, coupled with elevated L-type Ca
2+
current, as opposed to wild-type cells. RNA sequencing and proteomics assays indicated negative regulation of cardiac muscle contraction and ion channel activities, along with a positive enrichment of smooth muscle contraction genes in 75%KD cardiomyocytes/hearts. miR1 deficiency led to dysregulation of a wide gene network, with miR1’s RNA interference–direct targets influencing many indirectly regulated genes. Furthermore, after 6 weeks of bi-weekly intravenous tail-vein injection of miR1 mimics, the ejection fraction and fractional shortening of 75%KD hearts showed significant improvement but remained susceptible to arrhythmias.

CONCLUSIONS:
miR1 deficiency acts as a primary etiological factor in inducing cardiac remodeling via disrupting heart regulatory homeostasis. Achieving stable and appropriate microRNA expression levels in the heart is critical for effective microRNA-based therapy in cardiovascular diseases.
Magnesium and Hematoma Expansion in Intracerebral Hemorrhage: A FAST-MAG Randomized Trial Analysis
Authors: Liotta Eric M. , Maas Matthew B. , Prabhakaran Shyam , Shkirkova Kristina , Sanossian Nerses , Liebeskind David S. , Sharma Latisha , Stratton Samuel , Conwit Robin , Saver Jeffrey L. ,   for the FAST-MAG Investigators and Coordinators
Published: December 2023

BACKGROUND:
Observational studies suggest that magnesium may have hemostatic effects. FAST-MAG (Field Administration of Stroke Therapy-Magnesium) was a pragmatic clinical trial of magnesium sulfate administered prehospital for acute clinical stroke syndromes and included patients with intracerebral hemorrhage. Exploratory secondary analysis by the treatment group found no reduction in hematoma expansion (HE) associated with magnesium treatment in intracerebral hemorrhage but did not consider serum magnesium levels achieved. We analyzed FAST-MAG intracerebral hemorrhage data for associations between serum magnesium level, HE, and early neurological deterioration, accounting for groupwise biases.

METHODS:
HE was defined as hematoma volume increase ≥3 mL within 24 hours and early neurological deterioration as ≥1-point Glasgow Coma Scale decline from arrival to hospital day 4. Comparing treatment and placebo groups confirmed biased availability of neuroimaging data. Therefore, HE and neurological deterioration were analyzed and stratified by treatment and placebo groups using univariate tests and adjusted logistic regression.

RESULTS:

Spontaneous intracerebral hemorrhage was present in 381 patients. Placebo patients had fewer serial neuroimaging studies available (123 [65.4%] versus 145 [75.1%];
P
=0.038). Necessary data were available in 104 magnesium- and 85 placebo-treated patients (age, 64.9 [13.0] years; 67.7% male). In the magnesium group, higher magnesium level was associated with less HE (adjusted odds ratio, 0.64 per mg/dL [95% CI, 0.42–0.93]) and less neurological deterioration (adjusted odds ratio, 0.54 per mg/dL [95% CI, 0.33–0.82]). In the placebo group, magnesium level was not associated with either HE or neurological deterioration.

CONCLUSIONS:
Magnesium may exhibit a hemostatic effect that was only observable in the FAST-MAG magnesium treatment group. Equipoise should be maintained, and specific trials are needed.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT00059332.
Removing Backdoors in Pre-trained Models by Regularized Continual Pre-training
Authors: Zhu Biru , Cui Ganqu , Chen Yangyi , Qin Yujia , Yuan Lifan , Fu Chong , Deng Yangdong , Liu Zhiyuan , Sun Maosong , Gu Ming 
Published: December 2023

Abstract
Recent research has revealed that pre-trained models (PTMs) are vulnerable to backdoor attacks before the fine-tuning stage. The attackers can implant transferable task-agnostic backdoors in PTMs, and control model outputs on any downstream task, which poses severe security threats to all downstream applications. Existing backdoor-removal defenses focus on task-specific classification models and they are not suitable for defending PTMs against task-agnostic backdoor attacks. To this end, we propose the first task-agnostic backdoor removal method for PTMs. Based on the selective activation phenomenon in backdoored PTMs, we design a simple and effective backdoor eraser, which continually pre-trains the backdoored PTMs with a regularization term in an end-to-end approach. The regularization term removes backdoor functionalities from PTMs while the continual pre-training maintains the normal functionalities of PTMs. We conduct extensive experiments on pre-trained models across different modalities and architectures. The experimental results show that our method can effectively remove backdoors inside PTMs and preserve benign functionalities of PTMs with a few downstream-task-irrelevant auxiliary data, e.g., unlabeled plain texts. The average attack success rate on three downstream datasets is reduced from 99.88% to 8.10% after our defense on the backdoored BERT. The codes are publicly available at https://github.com/thunlp/RECIPE.
Drug therapy problems in patients with schizophrenia: A cross-sectional study
Authors: Temtem Gubae , Woldu Minyahil , Berha Alemseged , Shibeshi Workineh , Teferra Solomon , Engidawork Ephrem 
Published: December 2023

Introduction Fifty percent of people living with schizophrenia do not receive proper treatments, and adherence level has been reported as low as 65%. Furthermore, the level of satisfaction has been reported to be very low in this population. Objective The purpose of this study was to evaluate treatment satisfaction, adherence, and the prevalence of drug therapy problems (DTPs). Methods A hospital-based cross-sectional study was carried out on 118 patients with schizophrenia. DTPs, adherence, and treatment satisfaction were determined using the Cipolle, Morisky, Green, and Levine, and Treatment Satisfaction with Medicines Questionnaire tools. The data were then entered using Epi-Info™ version 7.2.1 and SPSS version 22 was used for analysis. Descriptive statistics were used to summarize patients’ characteristics. Univariate and bivariate logistic regressions, with a significance threshold of P < .05, were used to analyze the associations. Results DTPs were found in 52.5% ( P < .001) of the participants. The most often detected DTPs were ‘adverse drug reaction', (26.1%); ‘dose-too-low', (20.5%); and ‘ineffective-medicine therapy', (20.5%). Risperidone was the most prevalent medication (79, 47%) found in DTPs. DTPs were associated with age ≥ 65 years [AOR = .044, 95% CI (.003-.741); P < .030], drug-source [AOR = .774, 95% CI (.070-.826); P = .241], treatment duration [AOR = 5.820, 95% CI (1.451-23.342), P = .013], and the number of drugs taken [AOR = 5.936, 95% CI (1.623-21.71), P = .007]. Adherence status revealed that 69 (58.5%) of the participants were poorly adherent to their treatment. Overall, 68.8% of those who took part in the study were satisfied according to satisfaction ratings. Conclusions There is a high burden of DTPs in the study setting in the form of Adverse drug reactions, low dose schedules, and ineffective treatment associated with poor medication adherence; even though two-third of the participants were found to be satisfied with the clinical services given at the clinic.
Intensive care risk and long-term outcomes in pediatric allogeneic hematopoietic cell transplant recipients
Authors: Zinter Matt S. , Brazauskas Ruta , Strom Joelle , Chen Stella , Bo-Subait Stephanie , Sharma Akshay , Beitinjaneh Amer , Dimitrova Dimana , Guilcher Greg , Preussler Jaime , Myers Kasiani , Bhatt Neel S. , Ringden Olle , Hematti Peiman , Hayashi Robert J. , Patel Sagar , De Oliveira Satiro Nakamura , Rotz Seth , Badawy Sherif M. , Nishihori Taiga , Buchbinder David , Hamilton Betty , Savani Bipin , Schoemans Hélène , Sorror Mohamed , Winestone Lena , Duncan Christine , Phelan Rachel , Dvorak Christopher C. 
Published: December 2023

Abstract
Allogeneic hematopoietic cell transplantation (HCT) can be complicated by life-threatening organ toxicity and infection necessitating intensive care. Epidemiologic data have been limited by single-center studies, poor database granularity, and a lack of long-term survivors. To identify contemporary trends in intensive care unit (ICU) use and long-term outcomes, we merged data from the Center for International Blood and Marrow Transplant Research and the Virtual Pediatric Systems databases. We identified 6995 pediatric patients with HCT aged ≤21 years who underwent first allogeneic HCT between 2008 and 2014 across 69 centers in the United States or Canada and followed patients until the year 2020. ICU admission was required for 1067 patients (8.3% by day +100, 12.8% by 1 year, and 15.3% by 5 years after HCT), and was linked to demographic background, pretransplant organ toxicity, allograft type and HLA-match, and the development of graft-versus-host disease or malignancy relapse. Survival to ICU discharge was 85.7%, but more than half of ICU survivors required ICU readmission, leading to 52.5% and 42.6% survival at 1- and 5-years post-ICU transfer, respectively. ICU survival was worse among patients with malignant disease, poor pretransplant organ function, and alloreactivity risk factors. Among 1-year HCT survivors, those who required ICU in the first year had 10% lower survival at 5 years and developed new dialysis-dependent renal failure at a greater rate (P&lt;.001). Thus, although ICU management is common and survival to ICU discharge is high, ongoing complications necessitate recurrent ICU admission and lead to a poor 1-year outcome in select patients who are at high risk.
Klebsiella pneumoniae invasive syndrome with liver, lung, and brain abscesses complicated with pulmonary fungal infection: a case report and review of the literature
Authors: Luo Yunhao , Hu Wen , Wu Lingna , Duan Shijie , Zhong Xingmei 
Published: December 2023

Abstract
Background
Klebsiella pneumoniae invasion syndrome (KPIS) is a severe multi-site infection that is usually caused by hypervirulent Klebsiella pneumoniae. The bacteria are relatively common in Asian diabetics and can cause organ abscesses or sepsis. When patients develop intracranial infection, the prognosis is poor. After anti-infective treatment, the Klebsiella pneumoniae-induced liver and lung abscesses and pulmonary fungal infection were relieved, but the brain abscesses worsened. Such complex and severe infection cases are rarely reported. Early identification of intracranial infection, selection of antibiotics with high concentrations in cerebrospinal fluid, and active treatment of complications such as diabetes and fungal infection are of great significance for the prognosis of patients.

Case presentation
A 71-year-old patient diagnosed with liver abscess in another hospital was transferred to our hospital due to a worsening condition. On day 1 (day of admission), the patient was given invasive mechanical ventilation, continuous renal replacement therapy combined with endotoxin adsorption, antimicrobial treatment with imipenem-cilastatin, and percutaneous catheter drainage for liver abscess. Metagenomic next-generation sequencing in bronchoalveolar lavage fluid indicated Klebsiella pneumoniae (K. pneumoniae), Candida albicans, and Aspergillus flavus complex, and no viruses were detected. Blood and pus cultures revealed K. pneumoniae that was sensitive to piperacillin/tazobactam. The anti-infection therapy was adjusted to piperacillin/tazobactam combined with voriconazole. On day 14, a head computed tomography (CT) scan showed no significant changes, and a chest CT scan showed absorption of multiple abscesses in both lungs. The patient was still unconscious. After the endotracheal tube was removed, cranial magnetic resonance imaging (MRI) showed multiple brain abscesses. Finally, his family gave up, and the patient was discharged and died in a local hospital.

Conclusion
In cases of K. pneumoniae infection, the possibility of intracranial, liver, lung, or other site infections should be considered, and physicians should be vigilant for the occurrence of KPIS. For patients suspected of developing an intracranial infection, cerebrospinal fluid should be tested and cultured as soon as possible, a head MRI should be performed, and antibiotics with high distribution in cerebrospinal fluid should be used early. When patients are complicated with diabetes, in addition to glycemic control, vigilance for concurrent fungal infections is also needed.
IgMAT: immunoglobulin sequence multi-species annotation tool for any species including those with incomplete antibody annotation or unusual characteristics
Authors: Dorey-Robinson Daniel , Maccari Giuseppe , Hammond John A. 
Published: December 2023

Abstract
Background
The advent and continual improvement of high-throughput sequencing technologies has made immunoglobulin repertoire sequencing accessible and informative regardless of study species. However, to fully map dynamic changes in polyclonal responses precise framework and complementarity determining region annotation of rearranging genes is pivotal. Most sequence annotation tools are designed primarily for use with human and mouse antibody sequences which use databases with fixed species lists, applying very specific assumptions which select against unique structural characteristics. For this reason, data agnostic tools able to learn from presented data can be very useful with new species or with novel datasets.

Results
We have developed IgMAT, which utilises a reduced amino acid alphabet, that incorporates multiple HMM alignments into a single consensus to automatically annotate immunoglobulin sequences from most organisms. Additionally, the software allows the incorporation of user defined databases to better represent the species and/or antibody class of interest. To demonstrate the accuracy and utility of IgMAT, we present analysis of sequences extracted from structural data and immunoglobulin sequence datasets from several different species.

Conclusions
IgMAT is fully open-sourced and freely available on GitHub (https://github.com/TPI-Immunogenetics/igmat) for download under GPLv3 license. It can be used as a CLI application or as a python module to be integrated in custom scripts.
Integrated analysis of HSP20 genes in the developing flesh of peach: identification, expression profiling, and subcellular localization
Authors: Zhang Chunhua , Zhang Yanping , Su Ziwen , Shen Zhijun , Song Hongfeng , Cai Zhixiang , Xu Jianlan , Guo Lei , Zhang Yuanyuan , Guo Shaolei , Sun Meng , Li Shenge , Yu Mingliang 
Published: December 2023

Abstract
Background
Plant HSP20s are not only synthesized in response to heat stress but are also involved in plant biotic and abiotic stress resistance, normal metabolism, development, differentiation, survival, ripening, and death. Thus, HSP20 family genes play very important and diverse roles in plants. To our knowledge, HSP20 family genes in peach have not yet been characterized in detail, and little is known about their possible function in the development of red flesh in peach.

Results
In total, 44 PpHSP20 members were identified in the peach genome in this study. Forty-four PpHSP20s were classified into 10 subfamilies, CI, CII, CIII, CV, CVI, CVII, MII, CP, ER, and Po, containing 18, 2, 2, 10, 5, 1, 1, 2, 1, and 2 proteins, respectively. Among the 44 PpHSP20 genes, 6, 4, 4, 3, 7, 11, 5, and 4 PpHSP20 genes were located on chromosomes 1 to 8, respectively. In particular, approximately 15 PpHSP20 genes were located at both termini or one terminus of each chromosome. A total of 15 tandem PpHSP20 genes were found in the peach genome, which belonged to five tandemly duplicated groups. Overall, among the three cultivars, the number of PpHSP20 genes with higher expression levels in red flesh was greater than that in yellow or white flesh. The expression profiling for most of the PpHSP20 genes in the red-fleshed ‘BJ’ was higher overall at the S3 stage than at the S2, S4-1, and S4-2 stages, with the S3 stage being a very important period of transformation from a white color to the gradual anthocyanin accumulation in the flesh of this cultivar. The subcellular localizations of 16 out of 19 selected PpHSP20 proteins were in accordance with the corresponding subfamily classification and naming. Additionally, to our knowledge, Prupe.3G034800.1 is the first HSP20 found in plants that has the dual targets of both the endoplasmic reticulum and nucleus.

Conclusions
This study provides a comprehensive understanding of PpHSP20s, lays a foundation for future analyses of the unknown function of PpHSP20 family genes in red-fleshed peach fruit and advances our understanding of plant HSP20 genes.