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Abstract Perceptual learning, known to improve visual perception, demonstrates the plasticity of brain processes underlying vision. Early studies, using the backward-masked texture discrimination task (TDT), focused on the lack of generalizing learning to stimulus features, relating learning specificity to the selectivity of the brain networks involved in the visual task. Learning was found to be highly specific to the stimulus features, as expected from the processing selectivity found in early visual areas as well as to the task employed in training, pointing to top-down effects. More recent studies demonstrate the generalization of learning to untrained features under specifically designed training procedures. Here we suggest that transfer of learning takes place when the trained and untrained stimuli and task activate overlapping brain processes. We tested the effect of TDT learning, under conditions with and without visual adaptation, on the contrast detection (CD) of localized Gabor targets, either alone or backward masked (BM). At the TDT peripheral-target location, we found that the transfer of learning between TDT to CD and BM occurs under the TDT adaptation condition, but not under the no-adaptation condition, whereas at the TDT center-target location we found that transfer occurs for both conditions. Our results suggest that learning generalization across experimental conditions depends on overlapping neural processes within brain networks, here dominated by the inhibitory effects involved in adaptation and in spatiotemporal masking. Importantly, increased adaptation during training, due to increased stimulus consistency, enabled the transfer of learning to other tasks limited by sensory adaptation.

Copyright of Journal of Anbar University for Law & Political Sciences is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Perceptual learning, known to improve visual perception, demonstrates the plasticity of brain processes underlying vision. Early studies, using the backward-masked texture discrimination task (TDT), focused on the lack of generalizing learning to stimulus features, relating learning specificity to the selectivity of the brain networks involved in the visual task. Learning was found to be highly specific to the stimulus features, as expected from the processing selectivity found in early visual areas as well as to the task employed in training, pointing to top-down effects. More recent studies demonstrate the generalization of learning to untrained features under specifically designed training procedures. Here we suggest that transfer of learning takes place when the trained and untrained stimuli and task activate overlapping brain processes. We tested the effect of TDT learning, under conditions with and without visual adaptation, on the contrast detection (CD) of localized Gabor targets, either alone or backward masked (BM). At the TDT peripheral-target location, we found that the transfer of learning between TDT to CD and BM occurs under the TDT adaptation condition, but not under the no-adaptation condition, whereas at the TDT center-target location we found that transfer occurs for both conditions. Our results suggest that learning generalization across experimental conditions depends on overlapping neural processes within brain networks, here dominated by the inhibitory effects involved in adaptation and in spatiotemporal masking. Importantly, increased adaptation during training, due to increased stimulus consistency, enabled the transfer of learning to other tasks limited by sensory adaptation. [ABSTRACT FROM AUTHOR]

Background and objective: β-Thalassemia is a common inherited disease in this region. A considerable number of transfusion-dependent β-thalassemia (TDT) patients suffer bone problems. The objective of this study was to evaluate bone mineral density in TDT patients using dual-energy X-ray absorptiometry (DEXA) scan. Methods: In this study, 53 TDT patients aged ≥10 years, together with 25 normal healthy individuals were enrolled. Their bone status was assessed using DEXA scan at lumber spine (L1-L4) and femoral neck. The effect of physical, biochemical, and hormonal characteristics on the bone mineral density (BMD) parameters were evaluated. BMD-Z score was used to assess the magnitude of bone disease. Results: The mean age of the patients was 21.3±7.8 years with male to female ratio 1.4:1. The values BMD parameters were significantly lower in the patients compared to the normal group. The mean values of BMD Z-core among the patients at lumber spine and femoral neck were -2.95±1.07 and -1.51±1.02 respectively. Among the patients, osteoporosis was detected in 69.8% and 13.2% in lumber spine and femoral neck respectively. None of the normal individuals had osteoporosis. Patients’ age. body mass index (BMI) and parathyroid hormone level had a significant association with BMD Z-score (P

Human terminal deoxynucleotidyl transferase (TdT) can catalyze template-independent DNA synthesis during the V(D)J recombination and DNA repair through nonhomologous end joining. The capacity for template-independent random addition of nucleotides to single-stranded DNA makes this polymerase useful in various molecular biological applications involving sequential stepwise synthesis of oligonucleotides using modified dNTP. Nonetheless, a serious limitation to the applications of this enzyme is strong selectivity of human TdT toward dNTPs in the order dGTP > dTTP ≈ dATP > dCTP. This study involved molecular dynamics to simulate a potential impact of amino acid substitutions on the enzyme's selectivity toward dNTPs. It was found that the formation of stable hydrogen bonds between a nitrogenous base and amino acid residues at positions 395 and 456 is crucial for the preferences for dNTPs. A set of single-substitution and double-substitution mutants at these positions was analyzed by molecular dynamics simulations. The data revealed two TdT mutants—containing either substitution D395N or substitutions D395N+E456N—that possess substantially equalized selectivity toward various dNTPs as compared to the wild-type enzyme. These results will enable rational design of TdT-like enzymes with equalized dNTP selectivity for biotechnological applications. [ABSTRACT FROM AUTHOR]

Copyright of bilig: Journal of Social Sciences of the Turkish World is the property of bilig: Journal of Social Sciences of the Turkish World and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The relationship between the expression of zinc finger transcription factor (Slug), terminal deoxyribonucleotidyl transferase (TdT), Y chromosome sex determination region related high-speed swimming frame factor 9 (SOX9) protein and clinicopathological features and prognosis of thymoma patients was analyzed. 113 cases of thymoma tissues and adjacent tissues surgically resected in our hospital were selected from May 2016 to November 2018. The positive expression of Slug, TdT and SOX9 protein was determined by immunohistochemistry. The relationship between the expression of Slug, TdT and SOX9 protein and the clinicopathological features and prognosis of thymoma patients was analyzed. The positive expression rates of Slug, TdT and SOX9 protein in thymoma tissues were higher than those in adjacent tissues (P<0.05). There was no significant difference in the positive expression of Slug, TdT and SOX9 protein in thymoma tissues in terms of age, gender, tumor diameter, whether combined with myasthenia gravis and whether accompanied by macrovascular invasion (P>0.05). The positive expression of Slug, TdT and SOX9 protein in thymoma tissues was significantly different in Masaoka-Koga stage and WHO classification (P<0.05). The positive expression of Slug, TdT and SOX9 protein in thymoma tissues was positively correlated with Masaoka-Koga stage and WHO classification (P<0.05). The 5-year overall survival rate in 113 thymoma patients was 81.42% (92/113), the 5-year survival rate in Slug positive group was lower than that in Slug negative group (70.18% VS 92.86%). the 5-year survival rate in TdT positive group was lower than that in TdT negative group (79.790% VS 89.57%), the 5-year survival rate in SOX9 positive group was lower than that in SOX9 negative group (79.35% VS 90.48% ) (χ² =9.669, 9.515, 17.008, P<0.05). Cox proportional hazard regression model analysis showed that, Masaoka-Koga stage (stageIII/stageIV), WHO classification (B2/B3), positive expression of Slug protein, positive expression of TdT protein and positive expression of SOX9 protein were independent risk factors affecting the prognosis of thymoma patients (HR: 3.518, 2.921, 4.536, 1.402, 2.921, P<0.05). The expression of Slug, TdT and SOX9 in thymoma tissues are high, the expression of the three proteins are relate to the Masaoka-Koga stage and WHO classification, and they are independent risk factor affecting the 5-year survival rate of thymoma patients. [ABSTRACT FROM AUTHOR]

The accelerated adoption of distance learning in post-pandemic times has resulted in increasing research publications and review studies in a short time. This necessitates the exploration of a large corpus of academic publications for effective distance learning and learning strategies. As distance learning stakeholders have assimilated the transactional approach to understanding distance learning, transactional distance theory (TDT) is relevant to understand ways to reduce the distance between learners and educators for maximum effectiveness of distance learning. Our study applies TDT to review distance learning from a supply perspective and as a tool to ensure the improved quality of distance learning. This paper has two key contributions: we have presented evidence synthesis and conducted a foresight exercise. Following preferred reporting items for systematic reviews and meta-analyses guidelines, 275 documents published between 1994 and 2022 were identified for review. Our analysis revealed patterns, relationships, and trends in the application of TDT in various distance learning contexts. Most TDT research is conducted in social sciences (83.7%), with computer science accounting for 42.6% of the studies. The course materials' structure and design have also received considerable attention, with around 40.0% of the research focused on this area. For distance learning, studies revolve around factors such as student engagement, satisfaction, and TDT, which examine the distance between learners and instructors in various learning environments. Through systematic review and metaanalysis, we identify the three thematic areas in TDT research on distance learning. We have chartered themes on the effect of alternate design distance learning platforms on learner success, pushing the development boundaries in distance learning success through TDT, and the practical processes for designing successful distance learning courses via TDT-based pedagogical frameworks. In doing so, we streamline research in TDT and distance learning thematically and provide insight into further work. In addition, this study analyzed the relationships between sustainable development goal (SDG) and TDT literature. The co-citation analysis suggested that the strongest links were observed between education and innovation (SDG 4 and SDG 9), followed by education and gender equality (SDG 4 and SDG 5). [ABSTRACT FROM AUTHOR]

β-thalassemia, a congenital genetic hematological disorder characterized by the decrease or absence of β-globin chains, leads to a decrease in levels of Hemoglobin A. The affected individuals can be categorized into two cohorts based on transfusion dependency: transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). Remarkably, despite the primary pathology lying in β-globin chain depletion, β-thalassemia also exhibits an intriguing association with iron overload. Iron metabolism, a tightly regulated physiological process, reveals a complex interplay in these patients. Over time, both cohorts of β-thalassemic individuals develop iron overload, albeit through distinct mechanisms. Addressing the diverse complications that arise due to iron overload in β-thalassemic patients, the utilization of iron chelators has gained a lot of significance. With varying efficacies, routes of administration, and modes of action, different iron chelators offer unique benefits to patients. In the Indian context, three commercialized iron chelators have emerged, showcasing a high adherence rate to iron chelator-based treatment regimens among β-thalassemic individuals. In this review, we explore the intriguing connection between β-thalassemia and iron overload, shedding light on the intricate mechanisms at play. We delve into the intricacies of iron metabolism, unveiling the distinct pathways leading to iron accumulation in these patients. Additionally, the therapeutic efficacy of different iron chelators in managing iron overload complications is mentioned briefly, along with the guidelines for their usage in India. Through this comprehensive analysis, we aim to deepen our understanding of β-thalassemia and iron overload, paving the way for optimized treatment strategies. Ultimately, our findings provide valuable insights into improving the care and outcomes of individuals affected by β-thalassemia.

Çalışmanın amacı Türkiye’nin Türk Devletleri Teşkilatı (TDT) asıl üye ülkeleri ve gözlemci üye ülkeleri ile olan ticaretinde hangi mal gruplarında karşılaştırmalı üstünlüğe sahip olduğunu, hangi mal gruplarında ise karşılaştırmalı üstünlüğe sahip olmadığını analiz etmektir. 1995-2021 dönemine ait SITC Rev. 3 basamak 1 veri setinin kullanıldığı analizler Açıklanmış Karşılaştırmalı Üstünlükler (AKÜ) yaklaşımına göre yapılmıştır. Elde edilen bulgulara göre Türkiye Azerbaycan’a karşı 0, 1, 7 ve 8 numaralı mal gruplarında; Kazakistan’a karşı 1, 4, 5, 7 ve 8 mal gruplarında; Kırgızistan’a karşı 1, 3, 4, 5, 6, 7 ve 8 mal gruplarında; Özbekistan’a karşı 1, 4, 5, 7 ve 8 mal gruplarında; Türkmenistan’a karşı 0, 4, 7, 8 ve 9 mal gruplarında ve Macaristan’a karşı ise 1, 6 ve 8 mal gruplarında karşılaştırmalı üstünlüğe sahip olduğu tespit edilmiştir. Türkiye'nin diğer TDT üyesi ülkelerle olan dış ticaretinde karşılaştırmalı üstünlüklerinin genel olarak benzer bir yapıya sahip olduğu sonucuna ulaşılmıştır.

β-thalassemia, a congenital genetic hematological disorder characterized by the decrease or absence of β-globin chains, leads to a decrease in levels of Hemoglobin A. The affected individuals can be categorized into two cohorts based on transfusion dependency: transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). Remarkably, despite the primary pathology lying in β-globin chain depletion, β-thalassemia also exhibits an intriguing association with iron overload. Iron metabolism, a tightly regulated physiological process, reveals a complex interplay in these patients. Over time, both cohorts of β-thalassemic individuals develop iron overload, albeit through distinct mechanisms. Addressing the diverse complications that arise due to iron overload in β-thalassemic patients, the utilization of iron chelators has gained a lot of significance. With varying efficacies, routes of administration, and modes of action, different iron chelators offer unique benefits to patients. In the Indian context, three commercialized iron chelators have emerged, showcasing a high adherence rate to iron chelator-based treatment regimens among β-thalassemic individuals. In this review, we explore the intriguing connection between β-thalassemia and iron overload, shedding light on the intricate mechanisms at play. We delve into the intricacies of iron metabolism, unveiling the distinct pathways leading to iron accumulation in these patients. Additionally, the therapeutic efficacy of different iron chelators in managing iron overload complications is mentioned briefly, along with the guidelines for their usage in India. Through this comprehensive analysis, we aim to deepen our understanding of β-thalassemia and iron overload, paving the way for optimized treatment strategies. Ultimately, our findings provide valuable insights into improving the care and outcomes of individuals affected by β-thalassemia. [ABSTRACT FROM AUTHOR]

Enzymatic oligonucleotide synthesis methods based on the template-independent polymerase terminal deoxynucleotidyl transferase (TdT) promise to enable the de novo synthesis of long oligonucleotides under mild, aqueous conditions. Intermediates with a 3' terminal structure (hairpins) will inevitably arise during synthesis, but TdT has poor activity on these structured substrates, limiting its usefulness for oligonucleotide synthesis. Here, we described two parallel efforts to improve the activity of TdT on hairpins: (1) optimization of the concentrations of the divalent cation cofactors and (2) engineering TdT for enhanced thermostability, enabling reactions at elevated temperatures. By combining both of these improvements, we obtained a ~10-fold increase in the elongation rate of a guanine-cytosine hairpin.

B-acute lymphoblastic leukemia (B-ALL) is commonly encountered in clinical practice. Patients present with increased percentage of lymphoblasts in bone marrow and/or peripheral blood. Immunophenotypic study by flow cytometry or immunohistochemistry is essential to establish the diagnosis. Paired box-5 (PAX5) is a B cell lineage protein and terminal deoxynucleotidyl transferase (TDT) is an immature marker, both of which are routinely tested in the pathologic workup of acute leukemia. In this report, we describe a case of B-ALL in a 37-year-old woman in which both PAX5 and TDT were negative. Next-generation sequencing test detected mutations in DNA methyltransferase 3 α and Fms related receptor tyrosine kinase 3 genes, which are frequently mutated in acute myeloid leukemia rather than B-ALL. The constellation of these rare findings in a single case signifies the importance of examining a wide panel of markers when the diagnosis of ALL is suspected.

Objectives The 2021 Society for Hematopathology and European Association for Haematopathology Workshop addressed the molecular and cytogenetic underpinnings of transformation and transdifferentiation in lymphoid neoplasms. Methods Session 4, "Transformations of Follicular Lymphoma," and session 5, "Transformations of Other B-Cell Lymphomas," included 45 cases. Gene alteration analysis and expression profiling were performed on cases with submitted formalin-fixed, paraffin embedded tissue. Results The findings from session 4 suggest that "diffuse large B-cell lymphoma/high-grade B-cell lymphoma with rearrangements of MYC and BCL2 " is a distinct category arising from the constraints of a preexisting BCL2 translocation. TdT expression in aggressive B-cell lymphomas is associated with MYC rearrangements, immunophenotypic immaturity, and a dismal prognosis but must be differentiated from lymphoblastic -lymphoma. Cases in session 5 illustrated unusual morphologic and immunophenotypic patterns of transformation. Additionally, the findings support the role of cytogenetic abnormalities—specifically, MYC and NOTCH1 rearrangements—as well as single gene alterations, including TP53 , in transformation. Conclusions Together, these unique cases and their accompanying molecular and cytogenetic data suggest potential mechanisms for and unusual patterns of transformation in B-cell lymphomas and indicate numerous opportunities for further study. [ABSTRACT FROM AUTHOR]

The specificity and sensitivity of microRNA (miRNA) detection play a vital role in the early diagnosis of cancer and the treatment of various diseases. Here, we constructed a fluorescent biosensor based on click chemistry-terminal deoxynucleotidyl transferase (ccTdT) combined with the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas)12a cascade amplification system to achieve ultrasensitive miRNA-21 detection. Target miRNA-21 was employed as a template for click chemistry ligation of two nucleic acid probes, the product of which can be combined with magnetic microbeads (MBs). Then the 3′-end of the ligated nucleic acid and complementary strand miRNA-21 was extended by TdT. The extended poly-T tails activated the trans -cleavage ability of CRISPR/Cas12a, cleaving the reporter gene to generate the fluorescent signal. The proposed biosensor has a wide linear detection range, from 1 pM to 105 pM, with detection limits as low as 88 fM under optimal experimental conditions. Hence, this fluorescent biosensor enables simple, sensitive detection of miRNAs and offers a promising analytical platform for clinical diagnostics and biomedical research. • A novel and rapid miRNA detection platform was developed. • The sensor integrated click chemistry, TdT and CRISPR/Cas12a for signal amplification. • The fluorescent biosensor showed good specificity and sensitivity for miRNA detection with a detection limit of 88 fM. [ABSTRACT FROM AUTHOR]

Increased thermogenesis in brown adipose tissue might have an obesity-reducing effect in humans. In transgenic mice, depletion of genes involved in creatine metabolism results in disrupted thermogenic capacity and altered effects of highfat feeding on body weight. Data analyses of a sex-stratified genome-wide association study (GWAS) for body mass index (BMI) within the genomic regions of genes of this pathway (CKB, CKMT1B, and GATM) revealed one sexdimorphic BMI-associated SNP in CKB (rs1136165). The effect size was larger in females than in males. A mutation screen of the coding regions of these three candidate genes in a screening group (192 children and adolescents with severe obesity, 192 female patients with anorexia nervosa, and 192 healthy-lean controls) identified five variants in each, CKB and GATM, and nine variants in the codingsequence of CKMT1B. Non-synonymous variants identified in CKB and CKMT1B were genotyped in an independent confirmation study group (781 families with severe obesity (trios), 320 children and adolescents with severe obesity, and 253 healthy-lean controls). In silico tools predicted mainly benign yet proteindestabilizing potentials. A transmission disequilibrium test in trios with severe obesity indicated an obesity-protective effect of the infrequent allele at rs149544188 located in CKMT1B. Subsequent correlation analyses in 1,479 individuals of the Leipzig Obesity BioBank revealed distinct correlations of CKB with the other two genes in omental visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT). Furthermore, between-subject comparisons of gene expression levels showed generally higher expressions of all three genes of interest in VAT than in SAT. Future in vitro analyses are needed to assess the functional implications of these findings. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the IRF6 gene polymorphisms in the etiology of the Non-syndromic Orofacial Cleft (NSOFC) population from Kerala. The study included a hundred case-parent triads of NSOFC from the Kerala Population. Genomic DNA was isolated from the trios. The polymorphisms rs2235371 and rs7552506 were genotyped using polymerase chain reaction (PCR) and the Sanger sequencing method. PLINK and haploview software were used for the statistical analysis. We found a substantial association of the rs2235371 (p-value = 0.0094, OR = 2.2) with NSOFC. The allelic TDT analysis 'A' allele of rs2235371 showed significant paternal transmission (p-value = 0.03, P_POO=0.506), whereas the 'C' allele of rs7552506 (p-value = 0.0094, P_POO=0.0527) showed an excess maternal transmission. The linkage disequilibrium (LD) values (D'= 0.83 and r2 =0.033) between rs2235371 and rs7552506 discovered that these two SNPs are not in strong LD. Haplotype A-G exhibited a significantly reduced risk for oral clefts (p=0.035). The current study revealed that polymorphism rs2235371 is associated with NSOFC. The rs2235371 appears to be significant with the trait in the paternal lineage but not when considering both lineages together. On the other hand, rs7552506 shows a significant association in the maternal lineage, with the pooled analysis approaching statistical significance. This study indicates that the IRF6 gene may be a risk factor for NSOFC in the Kerala population. • rs2235371 is associated with increased risk of NSOFC and NSCLP. • NSOFC shows paternal transmission of the A allele of rs2235371. • In NSOFC and NSCLP the C allele of rs7552506 shows maternal transmission. • The A-G haplotype is significantly associated with a reduced risk for NSOFC. [ABSTRACT FROM AUTHOR]

The Mucin1 (MUC1) protein, involved in cytoprotective and signaling pathways, is abnormally elevated in various cancers, making it a key cancer indicator. Exosomes, which reflect the status of their originating cells, offer potential for cancer diagnosis. Thus, developing a method to detect MUC1-positive exosomes is crucial for the early diagnosis of certain cancers. In this study, we developed a highly sensitive, specific, and simple UV–visible signal amplification method to detect MUC1-positive exosomes using terminal deoxynucleotidyl transferase (TdT). Initially, exosomes were captured on magnetic beads using a CD63 aptamer(apt). The Primer-AuNPs-MUC1 apt complex which we synthesized by low pH loading method was then attached MUC1 proteins on the surface of the exosomes to create a sandwich structure. TdT catalyzed the extension of Biotin-dATP at the 3′ end of the primer, introducing multiple biotin sites into the sandwich structure. These sites subsequently bound multiple streptavidin-horseradish peroxidase (streptavidin-HRP), which catalyzed the oxidative color change of the substrate, which can be detected by colorimetric method. This method can detect A549 exosomes in the range of 1.4E+6 to 4.2E+8 particles/mL and shows high specificity for cell lines with different MUC1 expression. Additionally, it successfully distinguished cholangiocarcinoma (CCA) patients (n=11) from healthy individuals (n=7) in clinical serum assays, demonstrating good performance in real sample detection. • Developed an exosome detection system based on the dual targets of MUC1 and CD63. • Utilizing aptamers to bind targets, stable and cheap. • The method is based on TdT to realize efficient and simple signal amplification. • The method demonstrates the potential of exosome-based cancer diagnosis. [ABSTRACT FROM AUTHOR]

Increased thermogenesis in brown adipose tissue might have an obesity-reducing effect in humans. In transgenic mice, depletion of genes involved in creatine metabolism results in disrupted thermogenic capacity and altered effects of high-fat feeding on body weight. Data analyses of a sex-stratified genome-wide association study (GWAS) for body mass index (BMI) within the genomic regions of genes of this pathway (CKB, CKMT1B, and GATM) revealed one sex-dimorphic BMI-associated SNP in CKB (rs1136165). The effect size was larger in females than in males. A mutation screen of the coding regions of these three candidate genes in a screening group (192 children and adolescents with severe obesity, 192 female patients with anorexia nervosa, and 192 healthy-lean controls) identified five variants in each, CKB and GATM, and nine variants in the coding sequence of CKMT1B. Non-synonymous variants identified in CKB and CKMT1B were genotyped in an independent confirmation study group (781 families with severe obesity (trios), 320 children and adolescents with severe obesity, and 253 healthy-lean controls). In silico tools predicted mainly benign yet protein-destabilizing potentials. A transmission disequilibrium test in trios with severe obesity indicated an obesity-protective effect of the infrequent allele at rs149544188 located in CKMT1B. Subsequent correlation analyses in 1,479 individuals of the Leipzig Obesity BioBank revealed distinct correlations of CKB with the other two genes in omental visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT). Furthermore, between-subject comparisons of gene expression levels showed generally higher expressions of all three genes of interest in VAT than in SAT. Future in vitro analyses are needed to assess the functional implications of these findings.

B cell antigen receptor (BCR) diversity increases by several orders of magnitude due to the action of terminal deoxynucleotidyl transferase (TdT) during V(D)J recombination. Unlike adults, infants have limited BCR diversity, in part due to reduced expression of TdT. Since human infants and young mice respond poorly to polysaccharide vaccines, such as the pneumococcal polysaccharide vaccine Pneumovax23 and Vi polysaccharide (ViPS) of Salmonella enterica serovar Typhi, we tested the contribution of TdT-mediated BCR diversity in response to these vaccines. We found that TdT+/- and TdT-/- mice generated comparable antibody responses to Pneumovax23 and survived Streptococcus pneumoniae challenge. Moreover, passive immunization of B cell-deficient mice with serum from Pneumovax23-immunized TdT+/- or TdT-/- mice conferred protection. TdT+/- and TdT-/- mice generated comparable levels of anti-ViPS antibodies and antibody-dependent, complement-mediated bactericidal activity against S Typhi in vitro To test the protective immunity conferred by ViPS immunization in vivo, TdT+/- and TdT-/- mice were challenged with a chimeric Salmonella enterica serovar Typhimurium strain expressing ViPS, since mice are nonpermissive hosts for S Typhi infection. Compared to their unimmunized counterparts, immunized TdT+/- and TdT-/- mice challenged with ViPS-expressing S Typhimurium exhibited a significant reduction in the bacterial burden and liver pathology. These data suggest that the impaired antibody response to the Pneumovax23 and ViPS vaccines in the young is not due to limited TdT-mediated BCR diversification.

Copyright of International Journal of Economics, Business & Politics (UEIP) is the property of International Journal of Economics, Business & Politics and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Moore established transactional distance theory (TDT) to grasp transactional distance in the context of distance learning. Research using TDT in distance, open, and online learning environments has been undertaken. However, there are information gaps about what constitutes progress, future directions, and research deficits pertaining to TDT in the context of distance education. This systematic literature review (SLR) used PRISMA to analyze 42 papers to close the knowledge gap. Currently, TDT research in distance learning integrates various theories and models; nevertheless, there is a movement toward acceptance models and how to incorporate more relevant theories within the framework of distance learning. Future studies should integrate other aspects such as student motivation, student acceptance of technology, and student preparedness and desire to utilize technology in learning environments. As most research samples students, a research gap involving instructors and heterogeneous groups is proposed. It is projected that quantitative research will predominate in the future, leaving qualitative and mixed approaches as areas of investigation. This review illuminates the developments, future agenda, and research needs pertaining to TDT in the context of distance learning. It might serve as a foundation for future study on TDT in the context of distance, open, and online education. [ABSTRACT FROM AUTHOR]

Copyright of Beykoz Akademi Dergisi is the property of Beykoz University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: Non-syndromic cleft lip with or without cleft palate (NSCL ± P) is one of the most common birth malformations. Currently, numerous susceptibility SNPs have been reported by GWA studies, however, the replications of them among NSCL ± P from Han Chinese were very limited. Design: In this study, we selected 16 SNPs around 1q32.2 based on the published GWA studies and replicated them among 302 trios with NSCL ± P from Han Chinese Population. The genotypic data was analyzed with FBAT, PLINK and R package. Setting: The study was conducted in a tertiary medical center. Patients, participants: 302 patients with CL ± P and their parents. Main outcome measures: To ascertain the genetic variants in 1q32.2 in patients with CL ± P in Han Chinese Population. Interventions: Blood samples were collected. Results: We found T allele (Z = 4.26, p = 0.00002) and T/T homozygotes (Z = 4.4, p = 0.000011) at rs12063989 was significantly over-transmitted among non-syndromic cleft lip with or without cleft palate (NSCL ± P). Conclusions: We found rs12063989 exhibited significant association with the occurrence of NSCL ± P, which would provide new evidence for the future study in the etiology of NSCL ± P. [ABSTRACT FROM AUTHOR]

Lymphoblastic lymphoma is a group of non‐Hodgkin lymphomas that account for approximately 2% of all lymphomas. This is a report of a case of a young girl presenting with a solitary scalp mass which was resected. Histopathological examination of the mass along with bone marrow analysis revealed primary cutaneous B‐cell lymphoblastic lymphoma. A nine‐year‐old girl presenting with an asymptomatic erythematous, non‐tender scalp mass present for 12 months was admitted. Skull and brain were intact and devoid of any pathological findings on computed tomography imaging. Systemic examination also showed no evidence of mass lesion in other parts of the body. The lesion was resected and referred for pathological analysis. Microscopic study revealed heavy diffuse dermal and subcutaneous infiltration of monomorphous medium‐sized mononuclear cells, with fine chromatin, scant cytoplasm, and variable nucleoli along with intact epidermis and presence of grenz zone. Tumor cells dissect through the collagen fibers. Extensive mitotic figures and focal infiltration of the skin adnexa are seen. IHC study revealed that TdT, CD79a, CD99, CD45, CD20, and Ki67 markers were positive. According to these findings, a definitive diagnosis of primary cutaneous lymphoblastic lymphoma of B cell type was concluded. The 1‐year follow up after necessary treatment revealed normal findings without traces of recurrence. Lymphoblastic lymphomas (LBL) are a neoplasm of immature B cells belonging to the B‐(B‐LBL) or T‐cell lineage (T‐LBL) that accounts for approximately 2% of all lymphomas. Lymphoblastic lymphoma (LBL) is similar to acute lymphoblastic leukemia (ALL) and the differentiation between these neoplasms is based upon proportion of involvement of lymphoblasts in bone marrow. It has a higher male to female predominance, higher incidence in older children and younger adults, and a relatively higher frequency of CNS and gonadal involvement. The differential diagnosis is based on immunohistochemistry study of B‐cell linage tumor markers. Cutaneous involvement is present in about one third of patients with B‐LBL but rarely in patients with ALL. [ABSTRACT FROM AUTHOR]

Busulfan and cyclophosphamide (BuCy)‐based regimen has been used as a standard myeloablative chemotherapy for haematopoietic stem cell transplantation in thalassemia. However, treosulfan‐based conditioning regimen has emerged due to concerns of toxicities. We retrospectively analysed the safety and efficacy of fludrabine/Bu/Cy/antithymocyte globulin (ATG) versus treosulfan/thiotepa/fludrabine regimens for Hematopoietic Stem Cell Transplant (HSCT) in transfusion‐dependent thalassemia (TDT) conducted at our institute (2013–2021). In 75 patients, 36 (48%) received Flu/Bu/Cy/ATG whereas 39 (52%) received Treo/Thio/Flu. Median age was 6 (1–12) and 9 (1–15) years, respectively. Number of patients with Classes I, II, and III were 14, 10, and 12 in Flu/Bu/Cy/ATG versus 2, 19, and 18 in Treo/Thio/Flu group, respectively. Graft was growth factor mobilized bone marrow in Flu/Bu/Cy/ATG versus peripheral blood stem cell in Treo/Thio/Flu group. Mean stem cell dose was 3.82 (2.2–9.1) versus 5 (1.65–8.01) 106/kg in Flu/Bu/Cy/ATG versus Treo/Thio/Flu group, respectively. Neutrophils and platelets engrafted at a median of 16 (14–21) and 16 (9–47) days in Flu/Bu/Cy/ATG and 15 (10–20) and 13 (9–41) days in Treo/Thio/Flu group. Median duration of follow‐up was 28 (23–32.9) months. Five (6.6%) patients had rejection (all secondary). Venoocclusive disease was observed in 2 (5.7%) versus 4 (10.3%) patients (p =.047), respectively. Flu/Bu/Cy/ATG had 4 (11.4%) patients with acute GVHD versus 15 (38.5%) patients which had significant impact on survival (p =.038). We observed chronic GVHD in 4 (11.4%) and 11 (28.2%) patients, respectively, with significant impact on survival (p =.031). Four (5.1%) patients had TRM in Treo/Thio/Flu group, in contrast to none in Flu/Bu/Cy/ATG group. Mixed chimerism was common in Flu/Bu/Cy/ATG {20 (57.1%)} versus Treo/Thio/Flu group {12 (30.1%)}. Five‐year Event Free Survival (EFS) and OS of entire cohort were 87% + 4% and 94% + 3%, respectively. Estimated TFS, EFS, OS of Flu/Bu/Cy/ATG versus Treo/Thio/Flu was 97.1% + 2.9% versus 89.2% + 5.1% (p =.251), 97 + 3% versus 80.7 + 6% (p =.041) and 100% versus 90.4 + 5% (p =.067), respectively. In our experience, Flu/Bu/Cy/ATG regimen is safe and effective even in high‐risk TDT. However, one needs to be vigilant for mixed chimerism. [ABSTRACT FROM AUTHOR]

Ultrasensitive and specific detection of cocaine is of great significance for monitoring cocaine abuse. Herein, a fluorescent aptasensor via coupling CRISPR-Cas12a, with magnetic nanoparticles (MNPs), split-aptamer, and terminal deoxynucleotidyl transferase (TdT), was developed for the detection of cocaine. In short, the complete cocaine aptamer is split into two parts, one is modified on magnetic nanoparticles (MNPs) and the other is free. The presence of cocaine will mediate the binding of these two segments. Then TdT will mediate the extension to form an ultra-long sequence that can bind with multiple CRISPR-Cas12a resulting in the trans-cleavage activity of CRISPR-Cas12a being triggered. Thence, the DNA reporter which is bi-labeled with fluorophore and quencher is cleaved resulting in the generation of a fluorescence signal. The developed fluorescent aptasensor realizes the detection of cocaine with excellent sensitivity and specificity. The detection limit is low down to 33 pM, and the linear range is from 330 to 1.65 × 105 pM. Most importantly, this fluorescent aptasensor can be successfully applied to the determination of cocaine in human plasma samples. [ABSTRACT FROM AUTHOR]

Background: Thalassemia is a common genetic disease in Southeast Asia. Red blood cell (RBC) transfusion is an essential treatment for severe forms of thalassemia. We performed a study to demonstrate RBC alloimmunization and other transfusion-related complications in patients with transfusion-dependent thalassemia (TDT).Study Design and Methods: A multi-center web-based registry of TDT was conducted in eight medical centers across Thailand. Thalassemia information, transfusion therapy, and transfusion-related complications were collected. Factors associated with each complication were demonstrated using the logistic regression analysis.Results: Of 1000 patients recruited for the study, 449 were males (44.9%). The mean age was 23.9 ± 15.4 years. The majority of patients, 738 (73.8%) had hemoglobin E/beta-thalassemia. In the study, 421 transfusion-related complications were reported from 357 patients (35.7%). Alloimmunization was the most common complication which was found in 156 patients (15.6%) with 284 positive antibody tests. The most frequent antibodies against RBC were anti-E (80/284, 28.2%) followed by anti-Mia (45/284, 15.8%) and anti-c (32/284, 11.3%). Age ≥3 years at initial blood transfusion, splenomegaly, higher frequencies, and volumes of transfusion were significant factors associated with alloimmunization. None of the patients had to terminate blood transfusion due to multiple alloantibodies. Other commonly seen complications were allergic reactions (130, 13.0%), autoimmune hemolytic anemia (70, 7.0%) and febrile non-hemolytic transfusion reaction (54, 5.4%).Conclusions: Transfusion-related complications, especially alloimmunization, were common among Thai patients with TDT. Extended RBC antigen-matching for the Rh system and Mia should be implemented to prevent the development of alloantibodies in multi-transfused patients. [ABSTRACT FROM AUTHOR]

T‐cell lymphoblastic lymphoma (T‐LBL) is frequently revealed by amediastinal mass or peripheral lymphadenopathy. Skin lesions in T‐LBLusually present as multiple nodules associated with multiple peripherallymphadenopathy and bone marrow invasion. Our patient is particular bythe revealing presentation of the lesions as Cutis verticis gyrate. T‐cell lymphoblastic lymphoma (T‐LBL) is frequently revealed by a mediastinal mass or peripheral lymphadenopathy. Skin lesions in T‐LBL usually present as multiple nodules associated with multiple peripheral lymphadenopathy and bone marrow invasion. [ABSTRACT FROM AUTHOR]

Abstract Background Thalassemia is the most prevalent single-gene disorder. Myocardial and hepatic iron depositions lead to complications and eventually death. We aimed to assess the diagnostic efficacy of magnetic resonance imaging T2* (MRI T2*) in quantifying iron overload in liver and heart in transfusion-dependent B-thalassemia major (TDT) children. Methods Prospective clinical study was carried on sixty children diagnosed with TDT. All of them underwent laboratory investigations, including CBC, serum iron, and ferritin levels. MRI T2* of the heart and liver was carried out to measure the iron overload and estimate the left ventricular ejection fraction (LVEF). Results Thirty-eight males and 22 females with TDT with a mean age of 13.23 years were included. Twenty cases (33.3%) had severe liver iron overload, while 36 (60%) had normal cardiac iron. There was a moderate significant negative association between hepatic and cardiac iron deposition (P = 0.03). All cases with severe cardiac iron overload had impaired LVEF below 56%. A non-significant positive association was noticed between cardiac iron deposition and LVEF in T2* (P = 0.08). A moderate negative significant association was detected between hepatic iron deposition and serum ferritin, while a fair negative significant association was found between serum ferritin and cardiac iron deposition with P values of 0.04 and 0.02, respectively. Conclusion MRI T2* is the gold standard for monitoring and follow-up of iron overload in the heart and liver. It should be routinely performed in all TDT children as liver iron, and serum ferritin do not reflect cardiac iron overload.

Testing truth-default theory, individual-level variation in lie frequency was parsed from within-individual day-to-day variation (good/bad lie days) by examining 116,366 lies told by 632 participants over 91 days. As predicted and consistent with prior findings, the distribution was positively skewed. Most participants lied infrequently and most lies were told by a few prolific liars. Approximately three-quarters of participants were consistently low-frequency liars. Across participants, lying comprised 7% of total communication and almost 90% of all lies were little white lies. About 58% of the variance was explained by stable individual differences with approximately 42% of the variance attributable to within-person day-to-day variability. The data were consistent with both the existence of a few prolific liars and good/bad lie days. [ABSTRACT FROM AUTHOR]

An indolent T‐lymphoblastic proliferation (iT‐LBP) is a rare benign disorder characterized by an abnormal expansion of immature T‐cells, which morphologically can mimic malignancy. Since the first case was described in 1999, dozens more have been reported in the literature. However, the epidemiologic, clinical, pathologic, and biologic features of this disease have not been well described. Here, we retrospectively reviewed all known cases reported in the literature to better understand this entity. A PubMed search up to January 2022 highlighted 25 papers describing cases/case series of iT‐LBP, one of which was a case presentation in a slide workshop. Except for 9 of the cases in one of the papers, where it was evident that the number of CD3+/TdT+ cells were too few to conform with a diagnosis of iT‐LBP, all papers and all the cases reported were included in the study amounting to a total of 45 cases. Clinicopathologic characteristics were analyzed using descriptive statistics and frequencies. Our analysis highlighted the previously known association with Castleman disease and Castleman‐like features and underlined its association with dendritic cell proliferations in general, as well as uncovering high frequency of concurrence with hepatocellular carcinoma and autoimmune diseases, most notably myasthenia gravis, paraneoplastic pemphigus and paraneoplastic autoimmune multiorgan syndrome. Furthermore, the co‐expression of CD4 and CD8 and high prevalence of extranodal disease and recurrences were other less well described features that were revealed. [ABSTRACT FROM AUTHOR]

Topic Detection and Tracking technique (TDT) has been commonly used to identify the hot topics from the huge volume of Internet news information and keep up with the hot news. However, traditional topic detection and tracking methods have shown low accuracy and low efficiency. In this paper, a topic detection system driven by big data is built on the Spark platform, which aims at improving the efficiency of news collecting from the Internet and improving the accuracy and efficiency of topic detection and tracking tasks. This system can be easily employed in a distributed architecture and work as a parallelized news collecting and topic detection system. An improved density-based spatial clustering of application with noise (DBSCAN) clustering algorithm based on the time window is proposed to achieve accurate topic detection with the auxiliary advantage of reducing the time complexity. A parallel KNN based topic tracking algorithm is proposed for the topic tracking task. Experiments including comparison with some baseline algorithms and quantitative and qualitative analyses are conducted on pseudo-distributed Spark platform, which demonstrates the effectiveness and efficiency of the parallelized topic detection system.

Jun Zhou,1,* Suying Wang,2,* Lun Zhu,3 Luting Zhou,1 Hong Zeng,4 Yongli Gan,2 Chaofu Wang1 1Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pathology, Ningbo Clinical and Pathological Diagnostic Center, Ningbo, Zhejiang, People’s Republic of China; 3Department of Pathology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chaofu WangDepartment of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 2st Ruijin Road, Huangpu District, Shanghai, People’s Republic of ChinaEmail wangchaofu@126.comAim: The concrete features of expression of terminal deoxynucleotidyl transferase (TdT) are needed to be revealed in male and female germ cell tumors (GCTs).Methods: TdT immunostaining was performed in 195 GCTs, and the tumor and/or tumorous components included seminomas, germ cell neoplasias in situ (GCNISs), dysgerminomas, embryonal carcinomas (ECs), extragonadal germinomas, yolk sac tumors (YSTs), teratomas, and spermatocytic tumors. Twenty-one sex cord-stromal tumors were also added. Expression of the classical germ cell tumor markers (PLAP, OCT4, SALL4, CD117, and D2-40) was compared to that of TDT.Results: Nearly all (tumors or tumorous components) seminomas (99%, 107/108), GCNISs (98%, 51/52), dysgerminomas (94%, 17/18), ECs (100%, 15/15), and extragonadal germinomas (100%, 11/11) were positive for TdT. None of the cells in YSTs (0/38), teratomas (0/19), spermatocytic tumors (0/1), or sex cord-stromal tumors (0/21) were immunoreactive for TdT staining. The normal testicular and ovarian gonadal tissues were also negative for TdT. However, TdT presented with significant loss of antigen immunoreactivity in the paraffin-embedded tissues older than 3 years, giving rise to weak or moderate staining in a subset of cases. The expressions of TdT showed no significances with PLAP, OCT4, SALL4, CD117, and D2-40 during the diagnosis of the most GCTs (P> 0.05), except for with PLAP, SALL4, or CD117 in YST (P= 0.000 each), and D117 (P= 0.000) or D2-40 (P= 0.006) in ECs.Conclusion: Our findings further verify that TdT can serve as a new GCT marker for seminomas, GCNISs, dysgerminomas, ECs, and extragonadal germinomas, with a highly positive rate. Awareness of TdT positivity in GCTs contributes to the prevention of erroneous diagnoses, particularly in the setting of core needle biopsies. To determine the properties where TdT staining may not be apparent in some old archived paraffin-embedded tissues, one could circumvent the potential misinterpretations of false-negative immunohistochemistry results.Keywords: germ cell tumors, immunohistochemistry, TdT, pathological diagnosis

Abstract Background High-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6 is an aggressive mature B-cell neoplasm, whereas B-lymphoblastic lymphoma is immature cell proliferation, with a frequent positivity for terminal deoxynucleotidyl transferase. The transformation of a low-grade follicular lymphoma into a lymphoblastic neoplasm expressing terminal deoxynucleotidyl transferase is a very rare event. Case presentation A 55-year-old Caucasian man was followed for a grade 1–2 follicular lymphoma carrying a t(14;18) IGH/BCL2+ and was initially treated with R-CHOP. The follicular lymphoma presented two relapses. In the third relapse, the patient had multiple lymphadenopathy and ascites, which motivated a retroperitoneal biopsy and an ascitic tap. These samples were analyzed by histological, cytological, flow cytometric, cytogenetic, and molecular assessments. The patient died of a multiple organ dysfunction syndrome 2 weeks after his third relapse. The biopsy revealed a diffuse proliferation made up of two types of tumor cells: centroblasts (Bcl-6-positive) and immature cells (terminal deoxynucleotidyl transferase-positive). Flow cytometric analysis confirmed the immature phenotype, with an expression of terminal deoxynucleotidyl transferase, combined with a loss of membrane immunoglobulins. The cytogenetic analysis performed on the ascites revealed a clonal evolution characterized by a t(8;22)(q24;q11) MYC+ translocation not previously detected in follicular lymphoma. Fluorescence in situ hybridization confirmed the double rearrangement of the BCL2 and MYC genes. Polymerase chain reactions and sequencing were used to study the clonal relationship between follicular lymphoma and the secondary tumors. The IGVH gene rearrangement revealed a unique clonal rearrangement involving an IGVH4–59 subset in all three specimens. Conclusion These findings suggest a clonal relationship between the two types of lymphoma cells. Furthermore, they support the transformation of an acute follicular lymphoma into a composite lymphoma combining a high-grade B-cell lymphoma and a lymphoblastic neoplasm expressing terminal deoxynucleotidyl transferase. This case report highlights the possible transformation of follicular lymphoma into a highly aggressive and immature proliferation.

Abstract Background Thalassemia is a hereditary hemolytic anemia with a severity ranging from mild, non-transfusion dependent to severe chronic anemia requiring lifelong transfusion. Transfusional iron overload is a major complication in patients with transfusion-dependent thalassemia (TDT). Telomeres are sequences of nucleotides forming the end caps of chromosomes that act as a DNA repair system. Iron overload in thalassemia can cause increased oxidative stress which leads to cellular damage and senescence. This may result in telomere length shortening. The degree of telomere length shortening may reflect the severity of thalassemia. Methods This research aimed to study the leukocyte telomere length in patients with TDT in comparison to non-thalassemic individuals and to identify the clinical and laboratory parameters that are associated with telomere length. We conducted a cross-sectional study in patients with TDT aged ≥18 years. Leukocyte telomere length was measured by real-time quantitative PCR. Results Sixty-five patients with TDT were enrolled onto the study. There were 37 female patients (54.4%). The median age was 27 (18–57) years, and mean pre-transfusion hemoglobin level was 7.1 (± 1.07) g/dL. The mean telomere to single copy gene (T/S) ratios of patients with TDT and the controls were 0.72 ± 0.18 and 0.99 ± 0.25, respectively (p

Terminal deoxynucleotidyl transferase (TdT) is a unique DNA polymerase capable of template-independent extension of DNA. TdT's de novo DNA synthesis ability has found utility in DNA recording, DNA data storage, oligonucleotide synthesis, and nucleic acid labeling, but TdT's intrinsic nucleotide biases limit its versatility in such applications. Here, we describe a multiplexed assay for profiling and engineering the bias and overall activity of TdT variants with high throughput. In our assay, a library of TdTs is encoded next to a CRISPR-Cas9 target site in HEK293T cells. Upon transfection of Cas9 and sgRNA, the target site is cut, allowing TdT to intercept the double-strand break and add nucleotides. Each resulting insertion is sequenced alongside the identity of the TdT variant that generated it. Using this assay, 25,623 unique TdT variants, constructed by site-saturation mutagenesis at strategic positions, were profiled. This resulted in the isolation of several altered-bias TdTs that expanded the capabilities of our TdT-based DNA recording system, Cell HistorY Recording by Ordered InsertioN (CHYRON), by increasing the information density of recording through an unbiased TdT and achieving dual-channel recording of two distinct inducers (hypoxia and Wnt) through two differently biased TdTs. Select TdT variants were also tested in vitro , revealing concordance between each variant's in vitro bias and the in vivo bias determined from the multiplexed high throughput assay. Overall, our work and the multiplex assay it features should support the continued development of TdT-based DNA recorders, in vitro applications of TdT, and further study of the biology of TdT.