We investigate the substructure of jets produced in photoproduction events with center-of-mass energies √(s) = 30–140 GeV at the proposed Electron-Ion Collider (EIC). Events are generated using PYTHIA and contributions from direct and resolved photoproduction subprocesses are analyzed at different center-of-mass energies. Jets are reconstructed using longitudinally invariant k_T algorithm within the FastJet framework. Substructure of quark- and gluon-initiated jets in the selected di-jet photoproduction sample is studied in detail by using jet-shape variables. Predictions for subjet multiplicities and integrated jet shapes are presented in the gluon-initiated and quark-initiated jets. These results demonstrate the feasibility of distinguishing quark and gluon jets in the photo-production events at the EIC and provide a baseline for further QCD studies.

Fatigue significantly affects health-related quality of life (HRQoL) in patients with immune thrombocytopenia (ITP). However, the interplay between fatigue and cytokines in ITP remains poorly understood. This study included 100 patients with persistent or chronic ITP who had not received ITP-directed therapy in the previous 8 weeks and 50 age-matched healthy controls. Fatigue and HRQoL were assessed using the Functional Assessment of the Chronic Illness Therapy (FACIT) scale. Concurrently, plasma levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-17, and interferon-gamma (IFN-γ) were measured via enzyme-linked immunosorbent assay (ELISA). ITP patients had significantly lower total FACIT scores [median 146 (range 59–160]) and fatigue subscale scores [median 45 (range 9–52]) than controls [155 (149–159) and 49 (44–52), respectively; both p < 0.001]. IL-12 levels were significantly elevated in patients (313.2 vs. 95.5 pg/mL; p < 0.001) and showed a significant negative correlation with FACIT scores (Spearman’s ρ = –0.272, p = 0.007). Multivariate analysis revealed that female sex, longer disease duration among patients with chronic ITP (> 24 months), and elevated IL-12 levels were independently associated with greater fatigue and poorer HRQoL. ITP is associated with significant fatigue and HRQoL impairment, with IL-12 emerging as a potential immunological marker linked to this symptom burden.

Interaction between the RB1 tumor suppressor and human papillomavirus (HPV) oncoproteins is established; however, the reported prevalence of HPV in retinoblastoma varies widely (0–82

The presence of an M-band in serum and/or urine electrophoresis is a crucial diagnostic indicator for multiple myeloma and other plasma cell dyscrasias. Conventionally, on serum protein electrophoresis (SPEP), the M-band is observed as a sharp spike (M-spike), typically in the gamma region, occasionally in the beta region, and rarely in the alpha region. However, the infrequency of M-bands in the alpha region raises the possibility of overlooking them when coexisting with normal bands. This study underscores the significance of considering the potential discovery of M-bands in unusual sites, particularly in the alpha-2 region. This retrospective study spanned three years and involved conducting serum and urine protein electrophoresis followed by serum and urine immunofixation electrophoresis on a semi-automated platform (Helena Biosciences, Europe) using agarose gel and serum protein 6-band format kits. We identified five cases of multiple myeloma presenting with a monoclonal band in the alpha-2 region on SPEP and UPEP. Subsequent immunofixation electrophoresis confirmed these bands to be monoclonal bands in the lambda lane. In suspected cases of multiple myeloma, even in the absence of an M-band in the gamma region, heightened prominence in the alpha or beta region warrants further investigation through immunofixation electrophoresis (IFE).

Biomarkers are cellular, biochemical, or molecular substances generated by malignant tumors or their surrounding tissues that can be measured in various biological samples. Most biomarkers are tumor-associated rather than tumor-specific, and their levels are raised across a wide range of malignancies. Thus, tumor biomarkers have been proved as a diagnostic and prognostic tool in various malignancies. In the domain of gynecologic malignancies, tumor-associated biomarkers have been extensively explored owing to the invasive screening methods. Cancer antigen 125 (CA125) and CA19-9 have remained the only clinically employed biomarkers despite enormous attempts to discover novel biomarkers. Thus, exploration of new markers with improved sensitivity and specificity is need of the hour. Predictive genomic markers are now used in therapeutics, especially in molecular targeted drugs. Additionally, various epigenetic biomarkers like noncoding RNAs and inhibitors of DNA methylation and histone modifications are in preclinical stages or clinical trials. This chapter describes the biomarkers in endometrial and cervical cancer in detail.

Background: Dravet syndrome is an infantile-onset developmental and epileptic encephalopathy with limited data on the frequency of SCN1A in Indian children. The study aimed to identify and characterize the burden of SCN1A pathogenic variants associated with the Dravet syndrome phenotype through genetic testing in the North Indian population.Method: In this prospective, cross-sectional study from March 2015 to February 2019, we enrolled 52 children with Dravet syndrome phenotype who underwent genetic testing for SCN1A gene pathogenicity. We assessed variant effect using multiple algorithms, and genetic test results were reported based on recommendations from the American College of Medical Genetics and Genomics guidelines. Additionally, we performed multiplex-ligation dependent probe amplification (MLPA) to detect copy number variations of the SCN1A gene in children without identified genetic pathogenicity (n=22) and analysed the results using Coffalyser.net.Results: Of the 52 probands studied, pathogenic variants in the SCN1A gene were identified in 30 children. Among these variants, 11 truncating variants (3 frame-shift variants, 3 intronic variants in splice site regions, and 5 nonsense variants) in 12 unrelated probands, and 17 missense variants in 18 unrelated probands were found. The genetic yield of SCN1A pathogenicity in our cohort (n=52) was 58%. Additionally, two of the identified variants were novel. Furthermore, MLPA analysis of the SCN1A gene in 22 children without pathogenic variants yielded no results.Conclusion: This work represents a genetic analysis of a Dravet syndrome cohort, revealing a 58% burden of SCN1A variants in children with the Dravet syndrome phenotype from the North Indian population.

Introduction: Emerging evidence has shown that the glucagon-like peptide-1 (GLP-1) agonist can be used to treat Alzheimer disease; however, knowledge of its neural targets is limited. To understand the neural substrates of GLP-1, we have done whole brain mapping for GLP-1 and its receptor (GLP-1R), in 30 human brains.Methods: GLP-1 expression was studied by immuno-histochemistry and confirmed by the western blot method. The GLP-1R gene expression was studied by reverse transcription polymerase chain reaction.Results: GLP-1 expression was observed in most of the cortical areas (maximum in frontal, prefrontal and parietal cortex), diencephalon, and brainstem, but not in the cerebellum. Protein expression studies validated these results. The highest expression of GLP-1R was found in the frontal cortex. The orbitofrontal cortex and cerebellum had negligible expression. Hippocampus demonstrated a significant presence of GLP-1R but patchy immunoreactivity to GLP-1. GLP-1R presence in most of the human cortical regions and absence in the cerebellum is the major deviation from the animal brain. Sites that might be of interest in Alzheimer have been identified. GLP-1 demonstrated an age-related decline in most of the areas after the fifth decade. At 60 years, GLP-1 was not found in any of the cortical areas except in the prefrontal cortex; however, it was present in the sub-cortical areas.Conclusion: Age-related profiling of GLP-1 in various brain areas has been analyzed, which can have an important bearing on understanding Alzheimer disease. This study provides a detailed description of GLP-1 and an brain mapping for the first time and may lead to novel treatment options targeting the GLP-1 receptors.

Background: The KIR receptors present on the natural killer (NK) cells play a crucial role by exercising cytotoxicity to eliminate tumor cells. Both KIR and class-I HLA molecules exhibit extensive polymorphism. Although RB1 inactivation triggers the initiation of retinoblastoma; however additional immune alterations trigger tumor development. The aim was to explore the KIR/HLA polymorphism and its role in the pathogenesis of retinoblastoma.Methods: Patients with unilateral, non-familial retinoblastoma were enrolled as cases. Healthy individuals matched for ethnicity were enrolled as controls. KIR genotyping was performed by sequence-specific primer assay. The investigated KIR genes included: inhibitory (2DL1, 2DL2, 2DL3, 2DL4, 2DL5A, 2DL5B), activating (2DS1, 2DS2, 2DS3, 2DS4*FUL, 2DS4*DEL, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1) and pseudogenes (2DP1, 3DP1*FUL, 3DP1*DEL). In addition, HLA ligands were investigated by sequence-specific oligonucleotide assay for HLA-A, B, and C locus.Results: KIR genotyping was performed in 48 cases and 107 controls. The mean age of cases was 2.9 +/- 2.2 years (range: 0.25-10). Among the 19 KIR genes, the frequency of KIR2DS4*FUL (p = 0.0019) and 2DS5 (p = 0.0095) was increased among cases. HLA ligands were investigated in 25 cases and 50 controls. The frequency of HLA ligands (C1/C2, Bw4, A3/A11) was similar among cases and controls. However, the KIR/ HLA combination frequency for KIR3DS1/HLA-Bw4 was decreased in cases (p = 0.006).Conclusion: It is the pioneer study to report the association of killer cell immunoglobulin-like receptors in retinoblastoma. KIR2DS4*FUL and KIR2DS5 had a susceptible, and KIR3DS1/HLA-BW4 had a protective role in retinoblastoma. The results will aid in exploring the therapeutic potential of NK cell-based therapy for retinoblastoma.

Background. Presence of preformed donor specific antibodies (DSAs) detected by complement-dependent cytotoxicity (CDC-XM) is a strong contraindication for transplant. However, it has limitations including its sensitivity and its inability to distinguish between HLA-specific and other non-HLA-specific antibodies. In this study, we standardized CDC-XM by flow cytometry and determined its relevance by comparing its results with other methods of DSA detection, such as routine CDC-XM, antibody binding assay by flow cytometry (FC-XM), and Luminex-based crossmatch assays, such as Luminex crossmatch (LXM) and virtual crossmatch (VXM).Materials and Methods. A total of 79 serum samples were tested for DSAs by the flow cytometric complement-dependent cytotoxicity crossmatch assay (FC-CDC-XM) and then the results of FC-CDC-XM were compared with other detection methods such as CDC-XM, FC-XM, LXM, and VXM.Results. We found that the FC-CDC-XM assay is more sensitive than routine CDC-XM. Out of total 79 sera, 24 sera were detected positive (T cells positive: 1 case and B cells positive: 23) by FC-CDC-XM as compared with 3 sera using CDC-XM; these 3 sera also showed positivity by FC-CDC-XM. After FC-XM assay, 23 samples were positive by FC-XM and out of these 23 samples, 13 were also positive by FC-CDC-XM. On comparing the FC-CDC-XM results with VXM and LXM, 10 sera of 24 FC-CDC-XM positive had HLA class II antibodies detected on aConclusions. The FC-CDC-XM is a more sensitive and specific method for detection of HLA-specific complement-fixing antibodies than CDC-XM and FC-XM. FC-CDC-XM should be used in tissue-typing laboratories after intra- and inter- laboratory validation.

Background Serumimmunofixation electrophoresis (SIFE) and serumfree light chain ( SFLC) assay are imperative investigations in diagnosis and follow-up of multiple myeloma ( MM). SFLC assays are reported to have higher sensitivity than SIFE. However, discrepancies have been reported between them. The current study was aimed at assessing concordance and discordance between SIFE and SFLC results in MM. Methods A total of 450 observations of both SIFE and SFLC were obtained from treatment-naive and follow-up MM patients. Results One hundred and twenty-nine (28.7%) values were observed as discordant, that is, positive SIFE with normal SFLC ratio or negative SIFE with abnormal SFLC ratio ( p-value< 0.00001). Proportion of discordance was higher in SIFE positive-SFLC normal cases than SIFE negative-SFLC abnormal cases. Discordance was more frequent in follow-up cases. Conclusion Negative SFLC alonemay not be reliable forMMfollow-up. Algorithmmay be based on SFLCmeasurements on each follow-up till attainment of normal SFLC ratio. Once SFLC normalizes, follow-up may be done with SIFE. If SIFE is positive, further follow-up with SIFE may be initiated.