bluuebunny/crossref_metadata_2025_split huggingface dataset:
LIGHT (TNFSF14) Costimulation Enhances Myeloid Cell Activation and Antitumor Immunity in the Setting of PD-1/PD-L1 and TIGIT Checkpoint Blockade
Authors: Yoo Kyung Jin , Johannes Kellsey , González Louis E , Patel Arpita , Shuptrine Casey W , Opheim Zachary , Lenz Karen , Campbell Kristen , Nguyen Thuy-Ai , Miriyala Jayalakshmi , Smith Connor , McGuire Ashlyn , Tsai Yi-Hsuan , Rangwala Fatima , de Silva Suresh , Schreiber Taylor H , Fromm George 
Published: July 2022

Abstract
Coinhibition of TIGIT (T cell immunoreceptor with Ig and ITIM domains) and PD-1/PD-L1 (PD-1/L1) may improve response rates compared with monotherapy PD-1/L1 blockade in checkpoint naive non–small cell lung cancer with PD-L1 expression &gt;50%. TIGIT mAbs with an effector-competent Fc can induce myeloid cell activation, and some have demonstrated effector T cell depletion, which carries a clinical liability of unknown significance. TIGIT Ab blockade translates to antitumor activity by enabling PVR signaling through CD226 (DNAM-1), which can be directly inhibited by PD-1. Furthermore, DNAM-1 is downregulated on tumor-infiltrating lymphocytes (TILs) in advanced and checkpoint inhibition–resistant cancers. Therefore, broadening clinical responses from TIGIT blockade into PD-L1low or checkpoint inhibition–resistant tumors, may be induced by immune costimulation that operates independently from PD-1/L1 inhibition. TNFSF14 (LIGHT) was identified through genomic screens, in vitro functional analysis, and immune profiling of TILs as a TNF ligand that could provide broad immune activation. Accordingly, murine and human bifunctional fusion proteins were engineered linking the extracellular domain of TIGIT to the extracellular domain of LIGHT, yielding TIGIT-Fc-LIGHT. TIGIT competitively inhibited binding to all PVR ligands. LIGHT directly activated myeloid cells through interactions with LTβR (lymphotoxin β receptor), without the requirement for a competent Fc domain to engage Fcγ receptors. LIGHT costimulated CD8+ T and NK cells through HVEM (herpes virus entry mediator A). Importantly, HVEM was more widely expressed than DNAM-1 on T memory stem cells and TILs across a range of tumor types. Taken together, the mechanisms of TIGIT-Fc-LIGHT promoted strong antitumor activity in preclinical tumor models of primary and acquired resistance to PD-1 blockade, suggesting that immune costimulation mediated by LIGHT may broaden the clinical utility of TIGIT blockade.
Th2-Biased Transcriptional Profile Predicts HIV Envelope-Specific Polyfunctional CD4+ T Cells That Correlated with Reduced Risk of Infection in RV144 Trial
Authors: Cohen Kristen W , Tian Yuan , Thayer Casey , Seese Aaron , Amezquita Robert , McElrath M Juliana , De Rosa Stephen C , Gottardo Raphael 
Published: July 2022

Abstract
Ag-specific T cells play a critical role in responding to viral infections. In the RV144 HIV vaccine clinical trial, a rare subset of HIV-specific polyfunctional CD4+ T cells correlated with reduced risk of HIV-1 infection. Polyfunctional T cells are a subset of Ag-specific T cells that are able to simultaneously produce multiple effector cytokines. Little is known about what differentiates polyfunctional T cells from other vaccine-elicited T cells in humans. Therefore, we developed a novel live-cell multiplexed cytokine capture assay to identify, isolate, and transcriptionally profile vaccine-specific polyfunctional CD4+ T cells. We applied these methods to samples from subjects who received the RV144 vaccine regimen, as part of the HVTN 097 clinical trial. We identified two surface receptors (CD44 and CD82) upregulated on polyfunctional T cells and a Th2-biased transcriptional signature (IL-4, IL-5, and IL-13) that predicted the envelope-specific polyfunctional CD4+ T cell profiles that had correlated with reduced risk of HIV infection in RV144. By linking single-cell transcriptional and functional profiles, we may be able to further define the potential contributions of polyfunctional T cells to effective vaccine-elicited immunity.
Comprehensive Update and Revision of Nomenclature on Complement C6 and C7 Variants
Authors: Massri Mariam , Foco Luisa , Würzner Reinhard 
Published: July 2022

Abstract
Complement genes encompass a wide array of variants, giving rise to numerous protein isoforms that have often been shown to exhibit clinical significance. Given that these variants have been discovered over a span of 50 y, one challenging consequence is the inconsistency in the terminology used to classify them. This issue is prominently evident in the nomenclature used for complement C6 and C7 variants, for which we observed a great discrepancy between previously published works and variants described in current genome browsers. This report discusses the causes for the discrepancies in C6 and C7 nomenclature and seeks to establish a classification system that would unify existing and future variants. The inconsistency in the methods used to annotate amino acids and the modifications pinpointed in the C6 and C7 primers are some of the factors that contribute greatly to the discrepancy in the nomenclature. Several variants that were classified incorrectly are highlighted in this report, and we showcase first-hand how a unified classification system is important to match previous with current genetic information. Ultimately, we hope that the proposed classification system of nomenclature becomes an incentive for studies on complement variants and their physiological and/or pathological effects.
A Deep Learning Model for Accurate Diagnosis of Infection Using Antibody Repertoires
Authors: Chen Yuan , Ye Zhiming , Zhang Yanfang , Xie Wenxi , Chen Qingyun , Lan Chunhong , Yang Xiujia , Zeng Huikun , Zhu Yan , Ma Cuiyu , Tang Haipei , Wang Qilong , Guan Junjie , Chen Sen , Li Fenxiang , Yang Wei , Yan Huacheng , Yu Xueqing , Zhang Zhenhai 
Published: July 2022

Abstract
The adaptive immune receptor repertoire consists of the entire set of an individual’s BCRs and TCRs and is believed to contain a record of prior immune responses and the potential for future immunity. Analyses of TCR repertoires via deep learning (DL) methods have successfully diagnosed cancers and infectious diseases, including coronavirus disease 2019. However, few studies have used DL to analyze BCR repertoires. In this study, we collected IgG H chain Ab repertoires from 276 healthy control subjects and 326 patients with various infections. We then extracted a comprehensive feature set consisting of 10 subsets of repertoire-level features and 160 sequence-level features and tested whether these features can distinguish between infected individuals and healthy control subjects. Finally, we developed an ensemble DL model, namely, DL method for infection diagnosis (https://github.com/chenyuan0510/DeepID), and used this model to differentiate between the infected and healthy individuals. Four subsets of repertoire-level features and four sequence-level features were selected because of their excellent predictive performance. The DL method for infection diagnosis outperformed traditional machine learning methods in distinguishing between healthy and infected samples (area under the curve = 0.9883) and achieved a multiclassification accuracy of 0.9104. We also observed differences between the healthy and infected groups in V genes usage, clonal expansion, the complexity of reads within clone, the physical properties in the α region, and the local flexibility of the CDR3 amino acid sequence. Our results suggest that the Ab repertoire is a promising biomarker for the diagnosis of various infections.
Genomic and Transcriptional Mechanisms Governing Innate-like T Lymphocyte Development
Authors: Morgan Roxroy C , Kee Barbara L 
Published: July 2022

Abstract
Innate-like lymphocytes are a subset of lymphoid cells that function as a first line of defense against microbial infection. These cells are activated by proinflammatory cytokines or broadly expressed receptors and are able to rapidly perform their effector functions owing to a uniquely primed chromatin state that is acquired as a part of their developmental program. These cells function in many organs to protect against disease, but they release cytokines and cytotoxic mediators that can also lead to severe tissue pathologies. Therefore, harnessing the capabilities of these cells for therapeutic interventions will require a deep understanding of how these cells develop and regulate their effector functions. In this review we discuss recent advances in the identification of the transcription factors and the genomic regions that guide the development and function of invariant NKT cells and we highlight related mechanisms in other innate-like lymphocytes.
Adenosine Alleviates Necrotizing Enterocolitis by Enhancing the Immunosuppressive Function of Myeloid-Derived Suppressor Cells in Newborns
Authors: Zhou Dongmei , Yao Meng , Zhang Lijuan , Chen Yingying , He Juan , Zhang Yuxin , Xu Haixu , Zhou Pan , Zhong Wei , Yao Zhi , Zhou Jie 
Published: July 2022

Abstract
Necrotizing enterocolitis (NEC) is a common disorder in premature infants that is characterized by hyperinflammation and severe necrosis in the intestine. The pathogenesis of NEC remains to be elucidated. In this study, we demonstrate that adenosine, a metabolite more abundant in infants than in adults, plays an important role in the prevention of NEC. Administration of adenosine or its analog, adenosine-5′-N-ethyluronamide (NECA), dramatically relieved the severity of NEC in neonatal mice. Meanwhile, adenosine treatment significantly enhanced the immunosuppressive function, antibacterial activity, and migration of myeloid-derived suppressor cells (MDSCs). However, depletion of MDSCs or inhibition of their migration using the CXCR2 inhibitor SB225002 almost completely abrogated the protective effect of adenosine on NEC. Mechanistic studies showed that MDSCs in newborns expressed abundant adenosine receptor A2B (A2BR) that elicits intracellular cAMP signaling and its downstream target NF-κB. Importantly, intestinal tissues from patients with NEC showed significantly lower infiltration of A2BR-positive MDSCs than those from healthy donors. These observations revealed that adenosine-induced MDSCs represent an essential immune axis for intestinal homeostasis in newborns.
Plasmalogen-Mediated Activation of GPCR21 Regulates Cytolytic Activity of NK Cells against the Target Cells
Authors: Hossain Md Shamim , Mawatari Shiro , Fujino Takehiko 
Published: July 2022

Abstract
It is widely known that the immune system becomes slower to respond among elderly people, making them more susceptible to viral infection and cancer. The mechanism of aging-related immune deficiency remained mostly elusive. In this article, we report that plasmalogens (Pls), special phospholipids found to be reduced among the elderly population, critically control cytolytic activity of human NK cells, which is associated with activation of a cell surface receptor, G protein–coupled receptor 21 (GPCR21). We found the extracellular glycosylation site of GPCR21, which is conserved among the mammalian species, to be critically important for the activation of NK cells by Pls. The Pls-GPCR21 signaling cascade induces the expression of Perforin-1, a cytolytic pore-forming protein, via activation of STAT5 transcription factor. Inhibition of STAT5 abrogates GPCR21-mediated cytolytic activation of NK cells against the target cancer cells. In addition, oral ingestion of Pls inhibited cancer growth in SCID mice and inhibited the systemic spread of murine CMV in adult C57BL/6J mice. These findings advocate that Pls-GPCR21 signaling could be critical in maintaining NK cell function, and that the age-related reduction of this signaling cascade could be one of the factors behind immune deficiency in mammals, including humans.
The impact of social and institutional networks in sustaining South African rural small, medium and micro enterprises during the crisis
Authors: Farisani Tshililo R. 
Published: July 2022

Orientation: The coronavirus disease 2019 (COVID-19) and its subsequent variants, has exposed the ill-preparedness of Small, Medium and Micro enterprises (SMMEs) to grow and sustain themselves and, by extension, livelihoods after the pandemic induced socio-economic crises around the world.Research purpose: This study aimed to contribute to an understanding of the impact of social and institutional networks in sustaining South African rural SMMEs during the crisis in rural municipalities.Motivation for the study: Previous studies on the sustainability of South Africa’s SMMEs have identified challenges and opportunities for urban-based SMMEs without clarifying the roles of rural-based social and institutional networks. This study was an attempt to fill that gap.Research design, approach and methods: This qualitative research design used an interpretative research paradigm to achieve the research objectives. Data were collected from 34 purposively (social network analysis group interviews) and 35 snowballing (semi-structured one-on-one interviews) selected participants from two rural municipalities. Data were analysed using NVivo 12 software.Main findings: The findings of the study revealed that, in the absence of provincial and nationally based institutions, rural SMME supportive groups established alternative local social and institutional networks to sustain their SMMEs in the post-socio-economic crisis period.Practical/managerial implications: It is therefore recommended that all the institutions must work together to transform rural SMMEs from their unsustainable state to sustainability (post socio-economic crisis).Contribution/value-add: By drawing on the critical elements of the sustainable livelihoods framework and institutional theory, this study proposed a conceptual model for sustaining rural SMMEs during crisis.
Breastfeeding and autism spectrum disorder
Authors: Abd Elmaksoud Marwa S. , Aly Omneya , Abd Elfatah Magdy , Mahfouz Aml 
Published: July 2022

Background
Breastfeeding (BF) was suggested as an environmental factor that may confer a protective role against autism.

Aim
The primary aim was to compare the patterns of BF in children with autism spectrum disorder (ASD) with their typically developing siblings. The secondary objective was to conduct a pilot study to investigate the effect of BF on the severity of the core ASD symptoms and the intellectual functions among children with ASD.

Patients and methods
A comparative cross-sectional study was conducted at the Outpatient Clinic of Alexandria University Children’s Hospital on 100 children; 50 children with ASD (group A, n=50) and 50 typically developing children; siblings of children of group A (group B, n=50) using a designed semistructured questionnaire.

Results
The comparison between both groups revealed that neither BF ever, early initiation, prolonged duration, nor exclusive BF were statistically different in children with autism and their siblings. Among children with ASD, there was a significant positive relationship between early BF initiation and less severe core symptoms of autism on Childhood Autism Rating Scale scores (U=405, P=0.017) and better intellectual functions on intelligence quotient score (U=18, P=0.03). Exclusive BF had a weak significant positive correlation (r=0.31, P=0.03) with higher intellectual functions on the intelligence quotient score.

Conclusion
In conclusion, BF practices are not linked to autism in children at risk. However, because early BF initiation is connected to less severe ASD core symptoms, our study implies that BF can be regarded a predictive factor of optimal outcomes for children with ASD. Future research with a prospective design and a large sample size could aid in establishing a cause-and-effect relationship.
Linear growth response to growth hormone therapy in underweight versus normal weight short children
Authors: El Awwa Ahmed M.S. , Soliman Ashraf T. , El Siddig Suhair , Farag Marwa M. 
Published: July 2022

Introduction
Physiologically, growth hormone (GH) increases lean body mass and has a lipolytic function. However, long-term changes in weight status during GH treatment, as a function of pretreatment weight status have not previously been reported in large data sets.

Aim
To identify the growth response to GH therapy in those who were before treatment underweight versus normal weight short children.

Patients and methods
A retrospective study, we studied the auxologic data of 78 short, prepubertal children [height standard deviation score (HtSDS) less than −2 SDS below the mean for age and sex] with normal GH secretion [idiopathic short stature (ISS)]. Two groups were identified according to their pretreatment body mass index standard deviation score (BMISDS). Nineteen children were underweight (BMISDS < −2) and 59 children had normal BMISDS (>−2). All children received daily subcutaneous dose of GH (0.03–0.05 mg/kg/day) to keep their insulin-like growth factor-1 (IGF-1) level between 0 and 2 SD for 2 years.

Results
Before GH treatment, the underweight ISS group had significantly lower IGF-1 level versus the normal weight group with IGF-1 SD −1.633±0.766 SD versus −0.749±1.197 SD, respectively. Age and HtSDS did not differ among the two underweight and normal weight groups. Treatment with GH for 2 years was associated with a significant increase in the BMISDS in the underweight group (BMISDS increased by 0.45 SD) from −2.063±0.344 before treatment with GH versus −1.633±0.766 after treatment but not in the normal weight group. The HtSDS increased significantly in both groups after GH therapy, but the increase was greater in children with normal weight versus those with underweight as the increment in HtSDS was 0.42 and 0.374 SD, respectively. The difference of HtSDS from mid-parental HtSDS in low BMI versus normal BMI groups was −0.91 and −1.212 SD, respectively

Conclusions
GH therapy for 2 years significantly increased the IGF-1 level and improved BMISDS and HtSDS in underweight children with ISS. The BMISDS was better in the underweight group, but their HtSDS was less compared with the normal weight group.
Study of uric acid excretion in children with beta-thalassemia major attending Alexandria University Children’s Hospital
Authors: Hassanein Nehad , El Din Thabet Mohamed A. , Maarouf Dina , Mikhail Nevien 
Published: July 2022

Background
It is evident that high cell turnover rate is present in patients suffering from β-thalassemia. This is mainly the result of not only chronic hemolysis but also ineffective erythropoiesis. It is thus expected that hyperuricemia will occur.

Aim
Our study was conducted to study uric acid excretion in β-thalassemia major patients and to determine its relationship to tubular dysfunction in those patients.

Patients and methods
This case–control study was performed on 60 patients with β-thalassemia major and 15 children who were healthy and well, playing the role of the control group. Thorough history taking, review of medical records, and complete physical examination were done for all patients. Evaluation of uric acid excretion, glomerular and tubular renal functions were performed and compared between patients and the control group.

Results
Hyperuricemia was found in 48.8% of patients; however, none of the patients had evidence of gouty arthritis or nephrolithiasis. Serum uric acid (SUA) levels in patients who had positive correlation with serum creatinine, urine P/Cr ratio and urine uric acid/glomerular filtration rate (UUA/GFR), negative correlation with eGFR and no correlation with urine calcium/creatinine (UCa/UCr) ratio, blood urea nitrogen (BUN), urine β2 MG, and urinary uric acid/creatinine (UUa/UCr) ratio were assessed. The mean SUA level, BUN, serum creatinine, and levels of eGFR were significantly higher in β-thalassemia patients in comparison to the control group. Urinary P/Cr ratio, urine uric acid/ glomerular filtration rate (UUA/GFR) ratio, β-2 microglobulin levels, UCa/UCr, and UUa/UCr were also higher in β-thalassemia patients in comparison to the control group. The present study has a mean age of 8.62 years for the cases studied, and investigations in patients revealed the following results: mean SUA 5.17 mg/dl, mean BUN 16.58 mg/dl, mean serum creatinine 0.49 mg/dl, mean urine P/Cr ratio 1.40, mean eGFR 141.42 ml/min/1.73 m2, mean UUA/GFR 0.55, mean urine β2 MG 0.18 µg/ml, mean UCa/UCr 0.44, UUa/UCr 1.46, and these results were statistically significantly higher in patients compared with controls.

Conclusion
Renal dysfunction and hyperuricemia are prevalent among patients with β-thalassemia major, mostly related to hyperfiltration and tubular dysfunction. Early markers of tubular dysfunction (urine β2 MG, UCa/UCr, UUa/UCr) and glomerular dysfunction (urine P/Cr ratio and urinary uric acid/GFR ratio) should be followed up regularly in β-thalassemia major patients.
Prevalence of vitamin D insufficiency and deficiency among children with epilepsy
Authors: Bedar Hamdy M. , Mansour Amal R. , Ahmed Doaa H. , Elsakka Elham E. 
Published: July 2022

Background and aim
The relation between vitamin D, the use of antiepileptic drugs (AEDs), and bone integrity has been found in patients with epilepsy. The aim of the work was to study the prevalence of vitamin D insufficiency and deficiency among children with epilepsy, and to identify some possible risk factors.

Patients and methods
A comparative cross-sectional study was done on randomly chosen 60 children with epilepsy aged 3–15 years attending the neurology out-patient clinic and 20 healthy age-matched and sex-matched children, attending the pediatric outpatient clinic at Alexandria University Children’s Hospital from September 2014 to March 2015. They were divided into three groups: group I included 40 children receiving AED monotherapy for more than 1 year; group II included newly diagnosed epileptic children before receiving medications; group III included 20 healthy children as controls. History taking included patients’ age, sex, seizure history, nutritional history, sunlight exposure, associated illness or drug intake and history of vitamin D or calcium supplementation. Clinical examinations were done (systematic and neurological examination, weight and BMI). Laboratory investigations [liver and kidney function tests, serum calcium, phosphorus, alkaline phosphatase, and serum 25-hydroxyvitamin D (25(OH)D) levels] were done. Electroencephalogram was done for groups I and II.

Results
There was no significant difference between all groups regarding age and sex. The BMI was significantly different between groups II and III. Laboratory tests (alanine aminotransferase, aspartate aminotransferase, urea, creatinine, serum calcium, phosphorus, and alkaline phosphatase levels) showed no significant differences between the three studied groups. The mean of 25(OH)D among children in group I was significantly lower compared with children in group III. Females were associated with insufficient and deficient levels of vitamin D. There were statistically significant relations between 25(OH)D levels and BMI and the duration of AED treatment in group I.

Conclusion
The present study provides evidence of the increased prevalence of vitamin D insufficiency and deficiency among newly diagnosed children with epilepsy and in those on treatment with AEDs. In addition, the study has indicated that female sex, high BMI, AED use (carbamazepine, Na valproate) and prolonged duration of treatment are risk factors for vitamin D insufficiency and deficiency.