bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical Evaluation of Off-The-Shelf PD-L1+ Human Natural Killer Cells Secreting IL15 to Treat Non–Small Cell Lung Cancer
Authors: Lu Ting , Ma Rui , Mansour Anthony G. , Bustillos Christian , Li Zhiyao , Li Zhenlong , Ma Shoubao , Teng Kun-Yu , Chen Hanyu , Zhang Jianying , Villalona-Calero Miguel A. , Caligiuri Michael A. , Yu Jianhua 
Published: April 2024

Abstract
We described previously a human natural killer (NK) cell population that upregulates PD-L1 expression upon recognizing and reacting to tumor cells or exposure to a combination of IL12, IL18, and IL15. Here, to investigate the safety and efficacy of tumor-reactive and cytokine-activated (TRACK) NK cells, human NK cells from umbilical cord blood were expanded, transduced with a retroviral vector encoding soluble (s) IL15, and further cytokine activated to induce PD-L1 expression. Our results show cryopreserved and thawed sIL15_TRACK NK cells had significantly improved cytotoxicity against non–small cell lung cancer (NSCLC) in vitro when compared with non-transduced (NT) NK cells, PD-L1+ NK cells lacking sIL15 expression (NT_TRACK NK), or NK cells expressing sIL15 without further cytokine activation (sIL15 NK cells). Intravenous injection of sIL15_TRACK NK cells into immunodeficient mice with NSCLC significantly slowed tumor growth and improved survival when compared with NT NK and sIL15 NK cells. The addition of the anti-PD-L1 atezolizumab further improved control of NSCLC growth by sIL15_TRACK NK cells in vivo. Moreover, a dose-dependent efficacy was assessed for sIL15_TRACK NK cells without observed toxicity. These experiments indicate that the administration of frozen, off-the-shelf allogeneic sIL15_TRACK NK cells is safe in preclinical models of human NSCLC and has potent antitumor activity without and with the administration of atezolizumab. A phase I clinical trial modeled after this preclinical study using sIL15_TRACK NK cells alone or with atezolizumab for relapsed or refractory NSCLC is currently underway (NCT05334329).
Fine-grained hate speech detection in Arabic using transformer-based models
Authors: Bensoltane Rajae , Zaki Taher 
Published: April 2024

With the proliferation of social media platforms, characterized by features such as anonymity, user-friendly access, and the facilitation of online community building and discourse, the matter of detecting and monitoring hate speech has emerged as an increasingly formidable challenge for society, individuals, and researchers. Despite the crucial importance of hate speech detection task, the majority of work in this field has been conducted in English, with insufficient focus on other languages, particularly Arabic. Furthermore, most existing studies on Arabic hate speech detection have addressed this task as a binary classification problem, which is unreliable. Therefore, the aim of this study is to provide an enhanced model for detecting fine-grained hate speech in Arabic. To this end, three transformer-based models were evaluated to generate contextualized word embeddings from input sequence. Additionally, these models were combined with a bidirectional gated recurrent unit (BiGRU) layer to further improve the extracted semantic and context features. The experiments were conducted on an Arabic reference dataset provided by the open-source Arabic corpora and processing tools (OSACT-5) shared task. A comparative analysis indicates the efficiency of the proposed model over the baseline and related work models by achieving a macro F1-score of 61.68%.
A review on soft computing techniques used in induction motor drive application
Authors: Durgasukumar Gadwala , Prasad Repana Ramanjan , Gorantla Srinivasa Rao 
Published: April 2024

<div align="center"><table width="590" border="1" cellspacing="0" cellpadding="0"><tbody><tr><td valign="top" width="387"><p>In this paper, hybrid models based on fuzzy systems and neural networks are reviewed. A fuzzy inference system is explicitly represented by expertise for induction motor drives, incorporating the learning capability of artificial neural networks. Researchers have been attracted to neuro-fuzzy techniques for training and inference in induction motor drives due to their efficiency. According to the classification of research articles from 2000 to 2020, this article presents a review of different artificial neural network techniques, fuzzy and neuro-fuzzy systems. The main objective is to provide a concise overview of current neuro-fuzzy research and to enable readers to identify appropriate methods according to their research interests.</p><p> </p></td></tr></tbody></table></div>
Single-Cell RNA Sequencing Reveals an Immune Landscape of CD4
+
T Cells in Coronary Culprit Plaques With Acute Coronary Syndrome in Humans
Authors: Takeda Shintaro , Emoto Takuo , Yamashita Tomoya , Yamamoto Hiroyuki , Takaya Tomofumi , Sawada Takahiro , Yoshida Takeshi , Inoue Masatoshi , Suzuki Yuya , Hamana Tomoyo , Inoue Taishi , Taniguchi Masayuki , Sasaki Naoto , Otake Hiromasa , Ohkawa Takenao , Furuyashiki Tomoyuki , Kawai Hiroya , Hirata Ken-ichi 
Published: April 2024

BACKGROUND:
Acute coronary syndrome (ACS) involves plaque-related thrombosis, causing primary ischemic cardiomyopathy or lethal arrhythmia. We previously demonstrated a unique immune landscape of myeloid cells in the culprit plaques causing ACS by using single-cell RNA sequencing. Here, we aimed to characterize T cells in a single-cell level, assess clonal expansion of T cells, and find a therapeutic target to prevent ACS.

METHODS:

We obtained the culprit lesion plaques from 4 patients with chronic coronary syndrome (chronic coronary syndrome plaques) and the culprit lesion plaques from 3 patients with ACS (ACS plaques) who were candidates for percutaneous coronary intervention with directional coronary atherectomy. Live CD45
+
immune cells were sorted from each pooled plaque samples and applied to the 10× platform for single-cell RNA sequencing analysis. We also extracted RNA from other 3 ACS plaque samples and conducted unbiased TCR (T-cell receptor) repertoire analysis.

RESULTS:

CD4
+
T cells were divided into 5 distinct clusters: effector, naive, cytotoxic, CCR7
+
central memory, and FOXP3 (forkhead box P3)
+
regulatory CD4
+
T cells. The proportion of central memory CD4
+
T cells was higher in the ACS plaques. Correspondingly, dendritic cells also tended to express more HLAs (human leukocyte antigens) and costimulatory molecules in the ACS plaques. The velocity analysis suggested the differentiation flow from central memory CD4
+
T cells into effector CD4
+
T cells and that from naive CD4
+
T cells into central memory CD4
+
T cells in the ACS plaques, which were not observed in the chronic coronary syndrome plaques. The bulk repertoire analysis revealed clonal expansion of TCRs in each patient with ACS and suggested that several peptides in the ACS plaques work as antigens and induced clonal expansion of CD4
+
T cells.

CONCLUSIONS:

For the first time, we revealed single cell–level characteristics of CD4
+
T cells in patients with ACS. CD4
+
T cells could be therapeutic targets of ACS.

REGISTRATION:

URL:
https://www.umin.ac.jp/ctr
; Unique identifier: UMIN000040747.
Impact of Renal Denervation on Urinary Peptide-Based Biomarkers in Hypertension
Authors: Lauder Lucas , Siwy Justyna , Mavrogeorgis Emmanouil , Keller Felix , Kunz Michael , Wachter Angelika , Emrich Insa E. , Böhm Michael , Mischak Harald , Mahfoud Felix 
Published: April 2024

BACKGROUND:
Catheter-based renal denervation (RDN) reduces blood pressure in hypertension. Urinary peptides are associated with cardiovascular and renal disease and provide prognostic information. We aimed to investigate the effect of RDN on urinary peptide-based classifiers associated with chronic kidney and heart disease and to identify urinary peptides affected by RDN.

METHODS:
This single-arm, single-center study included patients undergoing catheter-based RDN. Urine samples were collected before and 24 months after RDN and were analyzed using capillary electrophoresis coupled with mass spectrometry. Predefined urinary peptide-based classifiers for chronic kidney disease (CKD273), coronary artery disease (CAD238), and heart failure (HF1) were applied.

RESULTS:

This study included 48 patients (33% female) with uncontrolled hypertension. At 24 months after RDN, systolic blood pressure (165±17 versus 148±20 mm Hg;
P
<0.0001), diastolic blood pressure (90±17 versus 81±13 mm Hg;
P
<0.0001), and mean arterial pressure (115±15 versus 103±13 mm Hg;
P
<0.0001) decreased significantly. A total of 103 urinary peptides from 37 different proteins, mostly collagens, altered following RDN. CAD238, a 238 coronary artery-specific polypeptide-based classifier, significantly improved following RDN (Cohen’s
d
, −0.632;
P
=0.0001). The classification scores of HF1 (
P
=0.8295) and CKD273 (
P
=0.6293) did not change significantly.

CONCLUSIONS:
RDN beneficially affected urinary peptides associated with coronary artery disease.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01888315.
LDL-c Lowering, Ischemic Stroke, and Small Vessel Disease Brain Imaging Biomarkers: A Mendelian Randomization Study
Authors: Dib Marie-Joe , Zagkos Loukas , Meena Devendra , Burgess Stephen , Chirinos Julio A. , Gill Dipender 
Published: April 2024

BACKGROUND:
The effects of lipid-lowering drug targets on different ischemic stroke subtypes are not fully understood. We aimed to explore the mechanisms by which lipid-lowering drug targets differentially affect the risk of ischemic stroke subtypes and their underlying pathophysiology.

METHODS:
Using a 2-sample Mendelian randomization approach, we assessed the effects of genetically proxied low-density lipoprotein cholesterol (LDL-c) and 3 clinically approved LDL-lowering drugs (HMGCR [3-hydroxy-3-methylglutaryl-CoA reductase], PCSK9 [proprotein convertase subtilisin/kexin type 9], and NPC1L1 [Niemann-Pick C1-Like 1]) on stroke subtypes and brain imaging biomarkers associated with small vessel stroke (SVS), including white matter hyperintensity volume and perivascular spaces.

RESULTS:
In genome-wide Mendelian randomization analyses, lower genetically predicted LDL-c was significantly associated with a reduced risk of any stroke, ischemic stroke, and large artery stroke, supporting previous findings. Significant associations between genetically predicted LDL-c and cardioembolic stroke, SVS, and biomarkers, perivascular space and white matter hyperintensity volume, were not identified in this study. In drug-target Mendelian randomization analysis, genetically proxied reduced LDL-c through NPC1L1 inhibition was associated with lower odds of perivascular space (odds ratio per 1-mg/dL decrease, 0.79 [95% CI, 0.67–0.93]) and with lower odds of SVS (odds ratio, 0.29 [95% CI, 0.10–0.85]).

CONCLUSIONS:
This study provides supporting evidence of a potentially protective effect of LDL-c lowering through NPC1L1 inhibition on perivascular space and SVS risk, highlighting novel therapeutic targets for SVS.
Near-Infrared II Photobiomodulation Preconditioning Ameliorates Stroke Injury via Phosphorylation of eNOS
Authors: Yokomizo Shinya , Kopp Timo , Roessing Malte , Morita Atsuyo , Lee Seeun , Cho Suin , Ogawa Emiyu , Komai Eri , Inoue Kazumasa , Fukushi Masahiro , Feil Susanne , Kim Hyung-Hwan , Bragin Denis E. , Gerashchenko Dmitry , Huang Paul L. , Kashiwagi Satoshi , Atochin Dmitriy N. 
Published: April 2024

BACKGROUND:
The current management of patients with stroke with intravenous thrombolysis and endovascular thrombectomy is effective only when it is timely performed on an appropriately selected but minor fraction of patients. The development of novel adjunctive therapy is highly desired to reduce morbidity and mortality with stroke. Since endothelial dysfunction is implicated in the pathogenesis of stroke and is featured with suppressed endothelial nitric oxide synthase (eNOS) with concomitant nitric oxide deficiency, restoring endothelial nitric oxide represents a promising approach to treating stroke injury.

METHODS:
This is a preclinical proof-of-concept study to determine the therapeutic effect of transcranial treatment with a low-power near-infrared laser in a mouse model of ischemic stroke. The laser treatment was performed before the middle cerebral artery occlusion with a filament. To determine the involvement of eNOS phosphorylation, unphosphorylatable eNOS S1176A knock-in mice were used. Each measurement was analyzed by a 2-way ANOVA to assess the effect of the treatment on cerebral blood flow with laser Doppler flowmetry, eNOS phosphorylation by immunoblot analysis, and stroke outcomes by infarct volumes and neurological deficits.

RESULTS:

Pretreatment with a 1064-nm laser at an irradiance of 50 mW/cm
2
improved cerebral blood flow, eNOS phosphorylation, and stroke outcomes.

CONCLUSIONS:
Near-infrared II photobiomodulation could offer a noninvasive and low-risk adjunctive therapy for stroke injury. This new modality using a physical parameter merits further consideration to develop innovative therapies to prevent and treat a wide array of cardiovascular diseases.
The Computational Turn in International Law
Authors: Lie Runar Hilleren , Langford Malcolm 
Published: April 2024

Abstract
The recent computational turn carries the potential to both enrich and destabilise international law research. Epistemologically, it offers a repertoire of data science methods, including network analysis, text processing and analysis, machine learning, and large language and agent-based models. Ontologically, with its inductive and macroscopic logic, it can inflect and challenge our established understandings of the nature and role of international law. In this article, we review the growing use of computational approaches in international law research, with a focus on their methodological particularity and potential contributions to doctrinal and non-doctrinal research questions. At the same time, we discuss the limitations of the computational turn, especially issues of suitability, quality, and feasibility.
The Chessboard Toghrās of Safavid Royal Decrees
Authors: Barati András 
Published: April 2024

Abstract
One of the most characteristic and resilient elements of state documents promulgated by the chancelleries of medieval and early modern Turkic Islamic empires is the toghrā, or calligraphic signature of rulers. In the administrative history of Iran, the chessboard toghrā constitutes a short and lesser-known variant. This royal emblem appeared during the Safavid period as the result of several administrative reforms. In this paper, I outline the development of the toghrā in medieval Iran on the basis of surviving documents and fragments and then offer a detailed portrait of the birth and brief life of the chessboard toghrā. Furthermore, the conspicuous similarity between this form and the toghrās of Mughal emperors precipitates a comparison and close analysis of their different elements and characteristics. Drawing on both published and unpublished royal decrees, this article explores the possible dimension of interrelation and provides insights into their similarities and differences in use and content.
Patterns and Characteristics of Amphetamine-type Stimulant Use in a North-eastern State of India: A Cross-sectional Study
Authors: Rao Ravindra , Ganesh Ragul , Kishore Kunal , Madan Ira , Khandpal Bhagwati , Sharma Charanjit 
Published: April 2024

Background: South Asia generally reports low levels of amphetamine-type stimulant (ATS) use, with few studies on the pattern of ATS use. We assessed the pattern of ATS use and associated high-risk behavior in Manipur, a north-eastern state of India. Methods: 209 adult male ATS users (mean age 28.8 years) from three districts of Manipur were interviewed. Data were collected on the patterns of high-risk behavior with ATS use, health consequences, and help-seeking. The severity of use with various substances was assessed using the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). Depression and anxiety were assessed by the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) scale, respectively. Results: The mean duration of ATS use was 3.7 years (SD 2.3). The majority used ATS almost daily (88%) and depended on ATS (77%). Methamphetamine (99.5%) was the most used ATS orally. Around 87% also suffered from opioid dependence. About 76% injected drugs, most commonly heroin. Almost three-fourths (78%) used ATS before their sexual intercourse, 31% of whom did not use condoms. Most reported physical problems with ATS and had above-cut-off scores on PHQ-9 and GAD-7. The majority (95%) reported that they could procure ATS easily. Also, the majority (93%) had thought of quitting ATS use. Discussion: Most ATS users start using ATS at a young age and have comorbid other drug use, including heroin. ATS use is associated with various physical and psychological problems. Focusing on ATS use in India and developing strategies to address this problem is essential.
Pursuit of Equity: Women on a Low Income Navigating Access to Health and Social Services in Canada
Authors: Duhn Lenora , Sparringa Michaela , Waite Jennifer , Camargo-Plazas Pilar 
Published: April 2024

Background Existing research highlights the role of social determinants of health, such as education and housing, in predicting health outcomes and the challenges that arise from deficiencies in these areas, often linked to societal inequities. Gender and income are recognized as social determinants of health, yet the complexities of their interplay, particularly for women with low income seeking health and social services in Canada, need more exploration. Objective This study investigates how gender and income intersect to affect access to health and social services for Canadian women with low income. Methods Employing a participatory action approach with arts-based and interpretive methodologies, the study partnered with a non-profit organization to engage five women through photovoice, interviews, and a focus group, aiming to capture their experiences in accessing services. Results The analysis revealed three primary themes: the labyrinth-like complexity of navigating health and social service systems, the importance of mental health sanctuaries, and the value of supportive networks. Participants reported difficulties and frustrations in system navigation, often feeling ignored by service providers. Contrarily, community agencies provided essential non-judgmental support, including daily necessities and emotional care, with the companionship of pets also being a notable source of comfort. Conclusion The findings advocate for a shift towards more person-centred care in health and social service systems to better serve women in vulnerable positions, emphasizing the need to simplify the process of accessing services and ensuring that service providers recognize and address the unique challenges faced by equity-deserving groups.
Examining Sexual Health Organizational Networks in Urban African American Communities Using Social Network Theory
Authors: Taylor Nina , Dolcini M. Margaret , Catania Joseph A. , Harper Gary , Cristobal Audrey , Timmons Tyler April 
Published: April 2024

Purpose Collaboration among organizations offering sexual health and youth development services has the potential to provide youth with effective sexual health support. However, formally structured efforts (eg, coalition formation) may be impractical or unsuitable for low-income communities where resources are often already limited. Social network theories provide an alternative approach for building collaborative organizational networks. Approach Research aims to evaluate the barriers and facilitators to collaboration in sexual health organizational networks. Setting Organizations in low income, urban, communities in Chicago and San Francisco that serve African American adolescents. Participants Providers (n = 22) from organizations that offer sexual health services and youth development services. Methods Focus groups (n = 4) were conducted and analyzed utilizing a combination of coding strategies. Results Barriers to collaboration included resource limitations and competition, differences in organizational roles and deliverables, and prejudice and stigma. Identifying common ground among organizations was found to be a facilitator to collaboration. Social network concepts in conjunction with study findings lead to the development of a practice model that hypothesizes a pathway for organizations to improve collaboration without formally structured efforts. Conclusion Our findings offer ways to encourage collaboration among organizations that support youth sexual health in low-income, urban, African American communities without relying on formal structures. Such collaborations may be critical for improving the provision of comprehensive sexual health support.
Home monitoring of fetal heart rhythm: Lived experiences of women with anti-SSA/Ro52 autoantibodies and their co-parents
Authors: Tingström Joanna , Öst Elin , Bergman Gunnar , Burström Åsa 
Published: April 2024

Objective The aim of this study was to explore the parents’ experiences of home monitoring of the fetal heart rhythm. Women with anti-SSA/Ro52 autoantibodies carry a 2%–3% risk of giving birth to a child with congenital heart block (CHB), following transplacental transfer and antibody-mediated inflammation in the fetal conduction system during 18th to 24th gestational week. Early detection and subsequent treatment have been reported to decrease morbidity and mortality. Therefore, home monitoring of the fetal heart rhythm by Doppler has been offered at our fetal cardiology center. This study was undertaken to explore the lived experience of the routine. Methods Participants were recruited from a single fetal cardiology center. Consecutive sampling was used. The inclusion criteria were women with SSA/Ro52 antibodies who had undergone Doppler examinations within the last two and a half years at the hospital and had monitored the fetal heartbeat at home. A semi-structured questionnaire was created, and the participants were interviewed individually. The interviews were transcribed verbatim and analyzed according to qualitative content analysis. Results The overall theme was defined as “walking on thin ice,” with six underlying categories: reality, different strategies, gain and loss, healthcare providers, underlying tension, and conducting the examinations again, all with a focus on how to handle the home monitoring during the risk period. Conclusion Both the mother and the co-parent expressed confidence in their own abilities and that the monitoring provided them with the advantage of growing a bond with the expected child. However, all the participants described a feeling of underlying tension during the risk period. The results show that home monitoring is not experienced as complicated or a burden for the parents-to-be and should be considered a vital part of the chain of care for mothers at risk for giving birth to a child with CHB. However, explaining the teamwork between the different caregivers, for the patients involved, their areas of expertise, and how they collaborate with the patient continues to be a pedagogic challenge and should be developed further.