bluuebunny/crossref_metadata_2025 huggingface dataset:
Candida albicans pathogenesis in the context of mucosal type II interferonopathy
Authors: Lubkin Ashira , Oikonomou Vasileios , Millet Nicolas , Swidergall Marc , Lionakis Michail S
Published: August 2023

Interferon-gamma (IFNγ) is a powerful cytokine that is crucial for adequate host defense. However, unchecked IFNγ can cause autoimmunity in several organs and can be directly toxic to host cells. Indeed, excessive IFNγ, or type II interferonopathy, occurs in several diverse disease states, including STAT1 gain-of-function mutations, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), Downs syndrome, and AIDS. We have recently shown that in APECED, which is caused by deficiency of autoimmune regulator (AIRE), excessive IFNγ leads to greater susceptibility to oral Candida albicans infection. C. albicans is both a normal member of the human microbiome and the most common human fungal pathogen. The ability of C. albicans to morph between commensal and pathogenic states is tied to its complex transcriptional regulation of virulence traits in response to environmental cues. Thus, we hypothesize that excessive IFNγ in the oral mucosa leads C. albicans to transition to a more virulent state. We are using transcriptomics to define the response of C. albicans to excess IFNγ. Further, we have found that during infection of oral epithelial cells, C. albicans becomes more invasive in the presence of IFNγ. Thus, we are also using metabolomics to investigate soluble mediators released by these cells in response to IFNγ. These experiments will shed light on C. albicans virulence regulation in response to autoinflammatory conditions. Further, this study will provide new insights into the dualistic nature of IFNγ — providing protection against many pathogens, while facilitating disease from a specific pathogen.

This work was supported by the Division of Intramural Research of the NIAID (ZIA AI001175).
An essential role for CD4+ T cells during Staphylococcus aureus craniotomy infection
Authors: Kak Gunjan , Horn Christopher M , Heim Cortney E , Kielian Tammy L
Published: August 2023

Treatment of brain tumors, epilepsy, or hemodynamic abnormalities requires a craniotomy to access the brain. Despite prophylaxis, infectious complications after craniotomy range from 1–3% with approximately half caused by Staphylococcus aureus (S. aureus). Using our novel mouse model of craniotomy infection, a critical role of CD4+ T cells was established since bacterial burdens were significantly increased in the brain, galea, and bone flap of RAG1−/− mice as well as following CD4+ T cell depletion. Bacterial burdens were also increased following anti-VLA-4 & LFA-1 treatment, further establishing a beneficial role for peripheral CD4+ infiltrates. Adoptive transfer of in vitro skewed Th1 or Th17 cells into RAG1−/− mice returned infectious burdens back to wild type (WT) levels. Ex vivo staining of transferred CD4+ T cells recovered from the brains of RAG1−/− mice revealed a dominant IFN-γ signature, even following Th17 adoptive transfer, suggesting that Th1 responses are critical for infection containment. Further evidence of Th1 and Th17 involvement was demonstrated by exacerbated infection in Tbet−/− and RORγt−/− mice, respectively. Interestingly, phenotypes were not evident in either IL-17A/F−/− KO or IFN-γ−/− mice, whereas adoptive transfer of CD4+ T cells from either IL-17−/− or IFN-γ−/− animals mitigated bacterial outgrowth in RAG1−/− mice, suggesting the combined action of Th1- and Th17-derived mediators. scRNA-seq identified an increased IFN-γ-regulated signature (gbp1/5, isg15, irf1, stat1) in select microglial and infiltrating granulocytic clusters. This suggests that T cell-innate immune cell crosstalk is necessary for bacterial containment during craniotomy infection.

R01 AI169788
Programming of checkpoint blockade responsive exhausted T cells by rheostatic IL-2 signals during priming by dendritic cells
Authors: Sarkar Surojit , Toumi Ryma , Xiao Hanxi , Pulliam Thomas , Reed Jim , Nghiem Paul , Kalia Vandana
Published: August 2023

Stem-like progenitor exhausted CD8 T cells are critical for maintaining long-term resistance during chronic infections and cancer, and represent an important checkpoint blockade immunotherapy target for functional reinvigoration and disease control. Here, we show a fate-deterministic role of rheostatic IL-2 signals and differential DC priming in programming the development of stem-like progenitor exhausted CD8 T cells during chronic viral infection. In vivo fate-tracking studies reveal that strong IL-2 signals during priming drive terminal differentiation. In contrast, tempered IL-2 signals are associated with TCF-1Hi stem-like precursors, which give rise to progenitor exhausted CD8 T cells, capable of long-term persistence and potent responsiveness to anti-PD-1 therapy in later stages of chronic viral infection. In the context of human tumors as well, single cell RNA-seq analyses of total or antigen-specific tumor infiltrating lymphocytes show an inverse relationship of IL-2 signaling signature with T cell stemness, as well as checkpoint blockade therapy outcomes in melanoma. Our studies further show that the rheostatic control of exhausted T cell fates by differential IL-2 signals is physiologically mediated through differential cell surface expression of IL-2Rα during early stages of T cell activation, which in turn is pioneered during priming by distinct dendritic cell subsets. Notably, moderation of in vivo IL-2 signals during priming promotes the development of stem-like TCF-1Hi lineage, thus supporting a unique strategy for improving clinical immunotherapy outcomes by enhancing the development of long-lived, therapy-responsive stem-like cells with vigorous effector expansion capabilities.

Pediatric Cancer Research Foundation to SS, the Rachel Lynn Henley Foundation to VK, the Hopes and Smiles For Children Foundation to VK, In Concert for Cancer Foundation to VK and the National Institutes of Health (CA254168 to TP; CA225517 to PN; AI132819, AI103748 to SS; 5P30CA015704; AI154363 to VK)
Pak2-mediated phosphorylation promotes RORγt ubiquitination and inhibits colonic inflammation
Authors: Kathania Mahesh , Kumar Ritesh , Lenou Elviche Taskem , Basrur Venkatesha , Theiss Arianne L , Chernoff Jonathan , K Venuprasad
Published: August 2023

Dysregulated Interleukin (IL)-17 expression and its downstream signaling is strongly linked to inflammatory bowel diseases (IBD). However, the molecular mechanisms by which the function of RORγt, the transcription factor of IL-17, is regulated remains elusive, which is absolutely necessary to develop advanced strategies to inhibit IL-17-mediated inflammation. By mass spectrometry-based approach, we have identified that Pak2, a Ser/Thr kinase, directly associates with RORγt. Pak2 recognizes a conserved KRLS motif within RORγt and phosphorylated the Serine (S) 316 within this motif. Genetic deletion of Pak2 in Th17 cells resulted in reduced RORγt phosphorylation, increased IL-17 expression and severe colitis upon adoptive transfer to Rag1−/− mice. Similarly, reconstitution of RORγt-S316A mutant in Rorc−/− Th17 cells resulted in enhanced IL-17 expression and colitis severity. Mechanistically, we demonstrate that Pak2-mediated phosphorylation causes a conformational change resulting in exposure of the ubiquitin ligase Itch interacting PPLY motif and degradation of RORγt. Thus, we have uncovered a novel mechanism by which the activity of RORγt is regulated that can be exploited therapeutically.

This work was supported by funds from the National Institutes of Health (R01-DK115668 and R01-AI155786) and Cancer Prevention Research Institute of Texas (RP160577 and RP190527), a translational pilot project grant from the Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center (23001045) to K.V., and R01-DK117001 to K.V. and A.L.T.
Unraveling myeloid cell-mediated mechanisms of resistance to immune checkpoint blockade in bladder cancer
Authors: Tran Michelle A , Farkas Adam M , Lee Karen , Horowitz Amir , Beaumont Kristin , Sebra Robert , Sfakianos John , Galsky Matthew , Bhardwaj Nina
Published: August 2023

Background

Only 15–25% of bladder cancer (BC) patients respond to PD-(L)1 immune checkpoint blockade (ICB) therapy. We previously used pre-treatment tumor to derive an ICB response gene signature that was enriched in adaptive immune genes and an ICB resistance signature enriched in innate immune and inflammatory genes.

Methods

We performed single-cell RNA sequencing (scRNAseq) on 27 bladder tumors and 3 normal-adjacent tissue specimens to resolve these signatures. We profiled tumor macrophages (MΦs) underlying the resistance signature with flow cytometry (FC). To recapitulate them, we used healthy donor blood monocytes differentiated with M-CSF, skewed with predicted ligands, and characterized by FC, RTqPCR, and bulk RNAseq. To examine for peripheral biomarkers, we conducted scRNAseq on paired blood and urine and performed O-Link and ELISA on plasma.

Results

Our ICB response and resistance signatures were enriched in distinct MΦ subsets: immunostimulatory (is)MΦs and pro-tumorigenic (pt)MΦs, respectively. ptMΦs upregulated SPP1, TREM1, and CLEC5A and pro-inflammatory and hypoxic programs whereas isMΦs upregulated antigen presentation and complement machinery. ptMΦs were enriched in tumor versus normal tissue. When we tested ptMΦ predicted drivers, IL-1β induced expression of Clec5a and Trem1 protein and transcription of SPP1, TREM1, and CLEC5A. In the first-ever BC urine scRNAseq, we discovered urine contains ptMΦs. Corresponding inflammatory cytokines (IL-1β, IL-6, IL-8) were elevated in advanced patient plasma compared to early stage and healthy donors. In conclusion, we identified pro-inflammatory SPP1+CLEC5A+TREM1+ MΦs that may underlie ICB resistance, be targeted via IL-1β and monitored via plasma and urine.

Supported by grants from NIH (F30 CA275269-01, R01 CA249175-01).
ON104, a novel antibody targeting oxidized Macrophage Migration Inhibitory Factor (oxMIF) shows efficacy in preclinical models of chronic inflammation
Authors: Ferhat Maroua , Landlinger Christine , Kerschbaumer Randolf , Tam Frederick W K , Nicoletti Ferdinando , Thiele Michael
Published: August 2023

Macrophage Migration Inhibitory Factor (MIF) is a pleiotropic inflammatory cytokine, ubiquitously present in various tissues and the circulation of healthy subjects. MIF is a primary counter-actor of glucocorticoids that emerged as a pivotal regulator of chronic inflammation. During inflammation, MIF converts into oxidized (ox)MIF which was described as the pathogenic and druggable isoform of MIF. ON104, a fully human antibody, was engineered to specifically neutralize oxMIF without triggering immune cell effector functions. ON104 was tested in three experimental models of chronic inflammatory diseases (CIDs): Glomerulonephritis (GN) in WKY rats, Collagen-Induced Arthritis (CIA) in DBA/1j mice; and adoptive T-cell transfer colitis in SCID mice. At disease onset, ON104 was administered at different dose levels twice a week for 1, 3, and 8 weeks in GN, CIA, and colitis, respectively. Clinical evaluations, blood and tissue sampling were done for all individual animals.

In the GN model, ON104 significantly reduced proteinuria, hematuria, and CD68+ macrophage infiltration within the inflamed kidneys. During CIA, ON104 ameliorated the severity of arthritis as indicated by reduced paw thickness, and decreased disease score. Furthermore, treatment with ON104 substantially attenuated clinical signs of colitis by preventing body weight loss and restoring stool consistency compared to the vehicle-treated controls.

Our findings substantiate the role of oxMIF in the pathogenesis of various CIDs. Thus, ON104 has the potential to become a well-tolerated therapeutic antibody for treating patients with CIDs.
Systemic administration of anti-CD20 indirectly reduces B cells in the inflamed meninges in a chronic model of central nervous system autoimmunity
Authors: Kerfoot Steven , Tesfagiorgis Yodit , Kemal Eden A , Craig Heather C , Parham Kate A
Published: August 2023

Anti-CD20 B cell depleting therapies have demonstrated that B cells are important drivers of disease progress in Multiple Sclerosis, although the pathogenic mechanisms are not well understood. A population of B cells accumulates in the inflamed meninges in MS and also in some chronic animal models of disease, typically adjacent to demyelinating lesions. The role of these meningeal B cells in disease is not completely understood, nor is their susceptibility to anti-CD20 therapy. Here, we administered anti-CD20 to 2D2 IgHMOG spontaneous experimental autoimmune encephalomyelitis mice in the chronic phase of disease, after the establishment of meningeal B cell clusters. Compared to the circulation, lymph nodes, and spleen, B cell depletion from the CNS was delayed and not evident until 7d post administration of anti-CD20. Further, we did not find evidence that anti-CD20 accessed meningeal B cells directly, but rather that depletion was indirect and the result of ongoing turnover of the meningeal population and elimination of the peripheral pool from which it is sustained. The reduction of B cell numbers in the CNS coincided with less demyelination of the spinal cord white matter and, surprisingly, an increase in the number of T cells in the meninges but not parenchyma.

YT is the recipient of an endMS Doctoral Studentships from the Multiple Sclerosis Society of Canada (MSSOC). KAP is the recipient of an endMS Post-Doctoral Fellowship from MSSOC. This study was funded by operating grants from the Canadian Institutes of Health Research and the MSSOC.
Stable Expression of FOXP3 and Core Tolerogenic Genes by Engineered Human Tregs
Authors: Zarin Payam , Sassone-Corsi Martina , Doherty Abigail , Chicoine Adam , DeVault Victoria , Li Xiang , Yam Jennifer , Wickham Thomas , Chen Tiffany , Depis Fabien
Published: August 2023

FOXP3+ Regulatory T cells (Tregs) play a critical role in the prevention of fatal autoimmunity and maintaining tissue homeostasis. The functional stability of Tregs remains critical in their contribution towards immune tolerance rather than runaway immunity, particularly for cell therapy whereby an inflammatory microenvironment may impact the expression of FOXP3 and associated tolerogenic genes. To address potential Treg instability, we generated human Engineered Tregs (EngTregs) through a gene editing approach of PBMC isolated CD4+ T cells, leading to stable FOXP3 expression and a rapamycin-activated signaling complex that provides tunable IL-2 signal, thereby effectively divorcing FOXP3 expression from existing regulatory elements known to promote Treg instability under inflammatory conditions. Using transcriptomic analysis, we evaluated the stability of cultured sorted Tregs (cTregs) compared to EngTregs. We found EngTregs expressed higher levels of key “Core Treg” and “FOXP3 Synergy” genes based on bulk and single cell RNA-seq analysis as confirmed by flow cytometry. Additionally, favorable expression pattern of key Treg stability markers, CD27, CD70 and IKZF4 (EOS) was observed in EngTregs compared to cTregs. Conversely, cTregs express higher levels of cytotoxic genes including GZMA and PERFORIN1 compared to EngTregs along with other inflammatory genes. Finally, we observed that these correlations have a functional implication as demonstrated by higher expression of key tolerogenic markers in EngTregs compared to cTregs. This work strongly supports EngTregs as stable, tolerogenic FOXP3+ T cells, thereby providing an invaluable asset for treating life-threatening autoimmune and autoinflammatory diseases.
Harnessing the Full Potential of Regulatory T Cells by mRNA-induced Antigen Specificity
Authors: Scott David W , Janssens Ibo , Van Delen Mats , Flumens Donovan , Dams Amber , Roex Gils , Van Den Bos Jasper , Campillo-Davò Diana , Packialakshmi Balamurugan , Cools Natalie
Published: August 2023

Regulatory T cells (Tregs) are crucial in inducing and maintaining tolerance, and already have shown clinical potential. In this study, we describe an efficient non-viral engineering method by TCR-encoding mRNA electroporation, while also exploring the potential of further promoting on-target effects by disrupting the endogenous TCR using a fully RNA-based CRISPR/Cas9 technology.

Endogenous TCR disruption prior to TCR-transfection resulted in more than 90% blockade of the endogenous TCR expression and a similar high (>85%) but more homogenous expression of the transgenic TCR. Importantly, following antigen-specific TCR-induced stimulation, both engineered Tregs significantly increased the expression of multiple activation and suppression markers. Moreover, the engineered Tregs outcompeted polyclonal Tregs in suppressing antigen-specific effector T cell proliferation and performed better in blocking moDC maturation, even in the presence of antigen-activated effector T cells. Secretome screening revealed a distinct anti-inflammatory profile for TCR-Tregs. On the other hand, TCR-engineered KO Tregs co-expressed anti-inflammatory cytokines together with some pro-inflammatory cytokines, but qualitatively different from their effector Th counterparts. Hence, an anti-inflammatory profile with Th cell features is seen with TCR-engineered KO Tregs. In conclusion, we show that this versatile approach can be used to induce the functional expression of a transgenic TCR, but also for CRISPR/Cas9-mediated disruption of endogenous TCRs with high efficiency using an RNA-based platform. Comparison between polyclonal Tregs and TCR engineered Tregs in EAE using an HLA-transgenic mouse model is now being investigated.

National Multiple Sclerosis Society (RG-1612-26484)
Determining antitumor responses to variable cadherin expression
Authors: Jordon Alexander R D , Fugere Céline , Borys Samantha , Brossay Laurent
Published: August 2023

Cancer immunotherapy has dramatically transformed the treatment of many cancers. Despite this, several limitations exist. For example, in some patients’ cancer can become resistant to immunotherapy and relapse is common. Therefore, it is essential to identify new targets for intervention. Our laboratory previously showed that KLRG1, which has two main ligands E-cadherin and N-cadherin, is a potential target. However, cadherin has many roles including a role in epithelial mesenchymal transition. To examine the KLRG1-cadherin axis in antitumor responses we used CRISPR/Cas9 and retroviral overexpression methods to develop a library of B16–F10 melanoma and 4T1 breast cancer cell lines with variable cadherin expression. The appropriate expression of E- and N-cadherin on the cells in this library was confirmed by both flow cytometry and Western blot. We then demonstrated that the modulation of cadherins does not alter cell proliferation rates in vitro. Importantly, in both models, we find that E-cadherin expressing cell lines cause significantly more mortality than E-cadherin deficient parental cell lines. Together, these findings suggest that the KLRG1-cadherin axis play an important role in antitumor responses.

This work was supported by the NIH research Grant R01 AI46709 (L.B.)
Siglec-7/9 are novel immune checkpoints for prostate cancer
Authors: Wen Ru , Stark Jessica C , Marti G Edward , García-Marqués Fernando , Zhao Hongjuan , Nolley Rosie , Bertozzi Carolyn R , Pitteri Sharon J , Brooks James D
Published: August 2023

Immune checkpoint-based therapy has led to striking improvements in survival in some types of cancer, but it is ineffective for others, including prostate cancer. Changes in glycosylation, particularly hypersialylation, have been found in diverse malignancies. Glycosylation can result in immune evasion through direct interactions of sialylated glycoproteins on cancer cell surfaces with Siglecs on immune cells including T cells, NK cells, and dendritic cells. Interactions between Siglec-7/9 and sialic acid have been implicated in inhibiting immune response in melanoma, leukemia, and lung cancer. Here, we found that Siglec-7/9 was highly expressed in immune cells including T cells and myeloid cells in the prostate cancer TCGA dataset. Immunohistochemistry demonstrated that Siglec-7/9 ligands were highly expressed in surgically resected prostate cancer tumor tissues but showed no or low expression in adjacent normal tissues. Siglec-7/9 ligands were also found in the prostate cancer cell lines. The disruption of Siglec-7/9 and their ligands by sialidase, which cleaves the sialic acid, or by anti-Siglec-7/9 blocking antibodies, promoted T cell-mediated cytotoxic killing of prostate cancer cells. Furthermore, anti-Siglec-7/9 treatment suppressed prostate cancer tumor growth in a humanized mouse model. Immunohistochemistry demonstrated that prostate cancers in mice treated with anti-Siglec 7/9 antibodies exhibited less Ki67 and CD31, and more cleaved caspase 3 and CD8 compared with the isotype control. This study provides insight into Siglec-7/9-sialic acid targeting strategies for prostate cancer and lays the groundwork for developing a novel class of immunotherapy-based drugs.

Supported by grants from DoD (W81XWH2110195) and NIH (#LINK#U01CA226051#ENDLINK#)
Weight-Loss Interventions and Levonorgestrel Intrauterine System Implantation for Early-Stage Endometrial Cancer and Atypical Endometrial Hyperplasia to Reduce Perioperative Risk of Severely Obese Patients
Authors: Isono-Taniguchi Roze , Tsubamoto Hiroshi , Inoue Kayo , Ueda Tomoko , Saeki Shinichiro , Takimoto Yumi , Wakimoto Yu , Shibahara Hiroaki
Published: August 2023

Endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) are associated with obesity, which increases the perioperative morbidity and surgical difficulties in laparoscopic and robotic surgery. Weight-loss interventions (WLIs) are likely to reduce morbidity; however, delayed surgery may cause cancer progression. To minimize the tumor progression, levonorgestrel intrauterine system (LNG-IUS) with minimal side effects was used until the planned surgery. During 2016 and 2021, we conducted preoperative management of WLI using LNG-IUS for seven highly obese women with a body mass index (BMI) ≥35 kg/m2 who had AEH and EC with Grade 1 and no myometrial invasion on magnetic resonance imaging. In three of the seven patients, the BMI decreased by more than 5. Two patients with AEH achieved remission after LNG-IUS placement and requested conservative management. Five patients with EC underwent laparoscopic hysterectomy, without perioperative complications.
Clinical Aspect of Pruritus in Pediatric Atopic Dermatitis: A Study from Western India
Authors: Shah Yogesh , Patidar Abhilasha , Meena Manju , Jain Manish , Mittal Asit , Balai Manisha
Published: August 2023

Introduction:

Atopic dermatitis (AD) is one of the most common dermatoses in the pediatric population and pruritus is its leading symptom; however, the clinical aspect of pruritus has not been studied much. The aim of the study was to explore clinical aspect of pruritus in pediatric AD and to analyze correlation of intensity of pruritus to the severity of AD.

Methods:

A hospital-based cross-sectional study of 106 pediatric patients of AD, between the age group of 6 months and 16 years was conducted. Diagnosis was made using the UK Working Party’s Diagnostic Criteria for AD. The severity of pruritus and sleep disturbances were assessed using the Numerical Rating Scale, and the severity of AD was assessed using SCORing of AD index.

Results:

Mean age at onset was 4.73 years and the mean duration of disease was 1.07 years. Pruritus was localized in 66.03%, intermittent in 89.7%, and continuous in 10.3%. Winter aggravation was observed in 36.8% and sleep disturbances were observed in 39.62%. “Pruritus intensity” was moderate or severe in 92% of patients and had significant correlation to the duration and severity of the disease, sleep disturbances, and coexistence of other atopic diseases.

Conclusion:

A pediatric patient with AD usually presents with localized or generalized, moderate or severe pruritus, and with sleep disturbances. Exacerbation of pruritus was the most common in winter and due to woolen garments and sweating. The intensity of pruritus was in direct proportion with the duration and severity of AD and coexistence of other atopic diseases.
Dermatitis Neglecta in a Case of Meningomyelocele
Authors: Padmawar Gauri , Gundewar Salil , Prakashey Arjun , Madke Bhushan
Published: August 2023

Dermatitis neglecta is a condition secondary to inadequate cleansing of the skin due to underlying causes such as pain, surgical site, neurological deficit, and neglect or psychocutaneous disorders. The result is an accumulation of keratin debris, sweat, sebum, and dirt giving a hyperkeratotic, hyperpigmented, and waxy appearance of the affected area. Soakage of the lesion with alcohol swabs and frictional cleaning of the area leads to the clearing of hyperkeratotic debris. We report a case of a 2-year-old male with dermatitis neglecta over meningomyelocele in the sacral region.
Evaluation of modified RENAL nephrometry score in the prediction of perioperative outcomes of open partial nephrectomy
Authors: Kamath K. Annappa , Pothy Vasudevan S. , Pandey Himanshu
Published: August 2023

Introduction:

RENAL nephrometry score (RNS) is a standardized system to grade the complexity of renal masses, but it does not correlate well with the perioperative outcomes of open partial nephrectomy (OPN). To overcome these shortcomings, a modified RNS (MRNS) has been proposed. In this study, we evaluated the MRNS and its role in predicting the perioperative outcomes of OPN.

Methods:

This was a prospective observational study performed at a tertiary care hospital to evaluate the efficacy of MRNS in predicting the perioperative outcomes of OPN. Sixty-four cases were included in the study. Demographic parameters, tumor characteristics, and perioperative outcomes were analyzed. Correlation with the post-operative outcomes and the strengths of MRNS were compared with various other nephrometry scores.

Results:

The mean age of the patients was 52.89 years, 60.9% were male and 53.1% had a right-sided mass. The comorbidities, body mass index, and performance scores were evenly distributed across the complexity groups (P > 0.05). The mean tumor size was 4.13 cm and the mean MRNS and RNS were 9.45 and 6.1, respectively. 60.9% of the cases had no complications. Major complications (Clavien–Dindo grade [CDG] 3+) were noted in five cases (7.8%). The trifecta of neargin, ischemia, and complications (MICs) score was achieved in 85.9% and was achieved in 71.9% of the cases. MRNS was found to be an independent predictor of the trifecta outcomes (P = 0.04). Receiver-operating characteristic curve of MRNS analyzing the major complications as per the CDG showed an area under the curve of. 804, indicating good prediction of complications by the MRNS.

Conclusions:

MRNS improves the predicting power of RNS by attributing enhanced scores to key elements and by adding new elements. Also, MRNS has good ability to predict the achievement of the trifecta and MIC.
Skip spondylolysis in a javelin thrower: A rare case report
Authors: Bharath Haranahalli Devendrappa , Gupta Anuj , Srivastava Abhishek
Published: August 2023

Pars interarticularis defects leading to spondylolysis and/or spondylolisthesis especially in young athletes are most commonly seen in lower lumbar vertebrae. Conservative treatment with abstinence from the athletic activities, rest, and physiotherapy marks the primary mode of treatment before going to surgical interventions. We report a 26-year-old patient with chronic lower back pain with antecedent history of athletic activities involving javelin throw. Besides an athletic activity, no other history of trauma existed. Radiologic investigations showed skip level pars lysis at L3 and L5 vertebrae. Patient was treated with only conservative methods, abstinence from sports and physiotherapy. Patient had significant improvement in his symptoms. Long-term proper physiotherapy to strengthen the lower back and abdominal muscles is necessary in order to alleviate the symptoms and to regain athletics. To our knowledge there are no reported cases where we find spondylolysis in upper lumbar vertebrae (L3), which is uncommon, along with most common L5 involvement in a young athletic javelin thrower. We have found only isolated L3/L4/L5 or concurrent L3 and L4 or L4 and L5 pars lysis reported in literature. There are no reported cases in literature on skip level spondylolysis in a single individual. Because of the natural history of the disease, conservative methods of management were aptly advocated and positive outcomes were seen in the follow-up.
Usefulness of imprint cytology for early diagnosis in vertebral lesions
Authors: Chadha Manish , Malhotra Raskesh , Bafna Lalit N , Bhateja Dheeraj , Wadhwa Neelam
Published: August 2023

Background:

Vertebral pathologies can be divided into degenerative, infective, or neoplastic. Infective and neoplastic lesions can progress rapidly and may lead to compression of the cord. Thus, rapid diagnosis for these lesions is important. Frozen section and fine-needle aspiration cytology techniques are less useful in hard bony tumors. Imprint cytology has been successfully used in the diagnosis of soft tissue tumors. The purpose of this study was to evaluate the role of imprint cytology in the early diagnosis of various spinal pathologies.

Materials and Methods:

Thirty-eight patients with suspected diagnosis of infection or tumor underwent transpedicular biopsy using Jamshidi needle. At least two imprint slides were made using core tissue obtained from biopsy. These slides were, thereafter, stained with the May-Grunwald–Giemsa method. The core biopsy sample was also sent for histopathological examination, after fixing it with 10% formalin. Paraffin-embedded blocks and slides were made for histopathology reporting, as per institution’s protocol. All imprint cytology slides were screened and reported by same pathologist.

Results:

The sensitivity of imprint cytology was 68.6%. Specificity, positive predictive value, negative predictive value, and overall accuracy of the imprint cytology were 100%, 100%, 21.4%, and 71%, respectively, when compared to histopathology. The mean duration of imprint cytology reporting was only 36 min while that for histopathological report was 15 days.

Conclusion:

Imprint cytology is a simple and rapid method for obtaining diagnosis in suspected vertebral lesions of infection or tumor. It is a reliable and cost-effective method in experienced hands. Although imprint cytology shows modest correlation in the ability to identify positive results, it forms a good diagnostic tool in confirming true negative cases with high diagnostic efficacy.
Cervicothoracic translational injury: Radiological analysis and risk factors of spinal cord injury
Authors: Ramachandran Karthik , Shetty Ajoy P , Naik Ashish S , Kanna Rishi M , Rajasekaran Shanmuganathan
Published: August 2023

Purpose:

To determine various radiological parameters predicting spinal cord injury (SCI) in patients with cervicothoracic translational injury.

Materials and Methods:

Forty-four patients operated for cervicothoracic (C7-T1) translational injury between January 2009 and 2019 were reviewed to obtain demographic details, mechanism of injury (based on Allen Ferguson classification), and neurology at the time of presentation (American Spinal Injury Association [ASIA] grade). Preoperative computed tomography scans were used to measure parameters like anterior translation, local kyphotic angle, residual canal diameter (RCD) at injury level/cranial level/caudal level, and magnetic resonance imaging scans were used to measure maximum canal compromise (MCC), maximum spinal cord compression (MSCC), and length of cord edema. Patients were divided into group 1 (complete neurodeficit), group 2 (incomplete neurodeficit), and group 3 (normal neurology), and the radiological predictors were compared.

Results:

In our study, anterior translation (P < 0.001), RCD at the injury level (P < 0.001), RCD at the caudal level (P < 0.001), MSCC (P < 0.001), and MCC (P < 0.001) were associated with the increased risk of SCI at the time of presentation. Comparison among all three patient groups showed significant differences in the above parameters. The optimal cutoff for risk of SCI is 7.8 mm for anterior translation, 8.6 mm for RCD at the injury level, 11.9 mm for RCD at the caudal level, 30% for MCC, and 24% for MSCC.

Conclusion:

Our data highlight that in addition to the amount of anterior translation, canal diameter, and the degree of spinal cord compression at the injury level, the RCD at the caudal level also determines the incidence of SCI in cervicothoracic translational injuries.
Fenestrated screws in osteoporotic spine—Is there an association between the cement distribution and DEXA scan T score?
Authors: Basu Saumyajit , Gala Rohan B , Biswas Amitava , Solanki Anil M
Published: August 2023

Purpose:

Cement distribution in spinal stabilization with fenestrated screws is unpredictable in patients with osteoporosis. The objective of our study was an assessment of cement distribution while using fenestrated screws and to establish an association between cement distribution and the Dual Emission X-ray Absorptiometry (DEXA) scan T scores.

Materials and Methods:

Osteoporotic patients who underwent spinal stabilization with fenestrated screws by a single surgeon with a minimum follow-up of one year were included. Cement distribution (four zones comprising the vertebral body and the pedicle), a pattern of distribution (concentrated or scattered) and cement leakage were assessed on CT scans. Patients were categorized into two groups based on their DEXA scan T scores to test an association between the pattern of distribution of cement and the scores. Clinical improvement was determined using visual analogue scale and Oswestry disability index scores.

Results:

A total of 126 screws were analyzed in 20 patients with a mean age of 69 years and a mean follow-up of 18 months. Out of 126 screws, 114 (90.47%) had cement in Zones 1 and 2. In total, 58 screws had a concentrated pattern of distribution of cement, whereas 68 screws had a scattered distribution, and the odds ratio of a scattered pattern of distribution was 6.31:1 if the DEXA scan T score was “below (−)3.0.” Clinical improvement was calculated in percentage of change from the preoperative value (mean % visual analogue scale change = 65.13 ± 7.59 and mean % Oswestry disability index change = 43.14 ± 7.24).

Conclusion:

The pattern of cement distribution in fenestrated screws relates well with the DEXA scan T scores and their usage should be strongly considered in patients with poorer scores. However, there is no relevant difference between the pattern of distribution and the clinical outcome.
Factors Associated with Early Complications of Surgical Management due to Penetrating Laryngotracheal Trauma in Colombia
Authors: López Mario-Fernando , Martínez Stella-Isabel , Carvajal Carlos-Andres
Published: August 2023

Background:

This investigation aimed to describe factors associated with early complications of surgical management due to penetrating laryngotracheal trauma in Colombia.

Materials and Methods:

A descriptive and retrospective cohort study was carried out; bivariate analysis using Pearson's Chi-square and Fisher's exact test was utilized to find associations with morbidity outcomes.

Results:

Between 2005 and 2019, 50 patients with penetrating laryngotracheal injuries underwent surgery; the median age was 29.5 years (interquartile ranges = 24.0–39.7), wherein 92% were male. The trachea was the most affected organ in 74% of patients, and lesions associated with laryngotracheal trauma were reported in 50% of patients. Cervicotomy was the surgical approach in 92% of patients. The 30-day overall morbidity was 24%, and mortality was 6%; dehiscence of the primary repair, or anastomosis, was present in 10% of the patients: 2% partial and 8% complete. Dehiscence was associated with infection (P = 0.002). Early stenosis was described in 10% of the patients; association was found between stenosis and dehiscence (P = 0.001), infection (P = 0.001), and reoperation (P = 0.001). Finally, infection was present in 8% of the patients and was indeed associated to the requirement of postoperative intensive care unit (ICU) hospitalization (P = 0.003).

Conclusions:

Limited information is available about factors related to early complications in laryngotracheal trauma. Nonetheless, in this series, a statistically significant association was found between early dehiscence of the primary repair, or anastomosis, and infection. Moreover, early stenosis was associated with dehiscence, infection, and reoperation. Finally, early infection was associated with the requirement of postoperative ICU hospitalization.
COVID-19 Vaccine Hesitancy amongst Residents of an Urban Field Practice Area: A Cross-Sectional Survey
Authors: Mitra Sayeli , Sarkar Arnab , Chowdhury Subhanil , Basu Rivu
Published: August 2023

Background:

Vaccines provide a crucial role in decreasing disease severity in COVID-19 infection. However, the accelerated pace of vaccine development has heightened public anxieties and could compromise acceptance. The World Health Organization has identified vaccine hesitancy as one of the top ten global health threats. There needs to be more community-based data on the causes of vaccine hesitancy of COVID vaccine in India, especially in the Eastern part.

Aims:

In this study, we intended to estimate the proportion of vaccine hesitancy in the community and elicit the reasons for COVID-19 vaccine hesitancy amongst the population of a slum in Kolkata.

Patients and Methods:

This was a descriptive observational study, cross-sectional in design conducted in the urban field practice area of a Tertiary Care Centre in Kolkata. Data were collected on the demography of the participants, awareness about COVID-19 and vaccination, willingness to accept the vaccine and willingness to pay for the COVID vaccine.

Results:

Most participants were willing to take the vaccine (73.95%). Amongst those who were not willing to take the vaccine (26.04%), the most common reason for not taking the vaccine was the concern about efficacy and safety. The willingness to pay for a single dose of the COVID vaccine ranged between 100 INR and 2000 INR with a median value of 250 INR.

Conclusion:

Transparent communication by the Government addressing the concerns of beneficiaries regarding vaccination may benefit the ongoing vaccination drive.
The Similarities and Differences between Liquid-based and Conventional Methods in Evaluation of Thyroid Fine Needle Aspiration Cytologies
Authors: Özer Mehmet , Özekinci Selver
Published: August 2023

Aims:

Thyroid nodules are one of the most frequent medical issues in endocrinology in our country and around the world. The appropriate evaluation of the nodule is critical in the management of patients. Fine needle aspiration cytology (FNAC) is one of the most accurate tools for evaluating these nodules. Conventional and liquid-based (LB) methods are available for thyroid FNAC. In this paper, we aim to determine the best cytological method for the evaluation of thyroid fine needle aspiration materials.

Settings and Design:

Fine needle aspiration (FNA) materials obtained and prepared by conventional and LB methods from 310 patients were evaluated. These slides were compared in terms of 12 cytological parameters in a three-tiered system, and the kappa coefficient was calculated.

Methods and Material:

Two slides were prepared from FNA samples, and the rest of the material was left in protective solution for LB cytology. Surepath was used as a LB technique. Conventional slides (CS) were left to dry in the air and stained with May Grunwald Giemsa. Slides prepared by two different techniques were compared in 12 cytomorphological parameters, and Kappa coefficients and correlations were calculated.

Statistical Analysis Used:

Kappa statistics.

Results:

In comparison of LB and CS, the highest kappa coefficient was in chromatin texture (ĸ:0.738) and inflammatory cells (ĸ: 0.482). On other parameters, fair or poor agreement was observed.

Conclusions:

Although there are some superiorities to LB cytology, co-application of these two methods is more favorable in thyroid fine needle aspiration.
INTRODUCTION AND IMPLEMENTATION OF INTERNAL FINANCIAL CONTROL IN GEORGIA
Authors: Mzhvanadze Aleksandre
Published: August 2023

Aleksandre Mzhvanadze

Email:aleksandremzhavanadze@gmail.com

PhD Student, Batumi Shota Rustaveli State University

Batumi, Georgia

https://orcid.org/0009-0003-4079-8416

 

Abstract. Reason of research. Raising awareness about financial management and control and timely response to existing challenges.

Methodology/approach. The methodological basis of the paper is the fundamental research of economic science. Georgian and foreign scientific articles, works and studies are used in the work, the material used in the research is based on the data of the Ministry of Finance of Georgia, the Ministry of Economy and Sustainable Development, and the National Statistics Service. Qualitative and statistical methods, data from international organizations are used in the research, this research is mainly based on information collection, comparison, study and analysis.

Research tasks. The main tasks and hypotheses of the research can be formulated as follows: the need to introduce the reform was determined not only by Georgia's obligations to the European Union, but also by the potential benefits obtained as a result of its introduction, because the state's internal financial control system ensures the proper functioning of public services and the legal and transparent use of state funds. , economical, efficient and productive disposal.

Practical value/consequences. The results and conclusions of the research can be used in higher education as a guide material. In addition, it will significantly help the government institutions in the development of the country's economic development course, its adjustment and implementation of specific issues.
Pengembangan Aplikasi Evaluasi Kegiatan Berbasis Android menggunakan Metode RAD (Rapid Application Development)
Authors: Subhiyakto Egia Rosi , Agustina Feri , Reswara Charesta Vida
Published: August 2023

The development of technology is very fast, especially in the field of information systems. Companies, organizations, schools and governments definitely need the role of information technology in data security or management. The use of the internet is very much needed in government agencies because the internet is used as a means to provide fast and easy services to people who want to handle important documents. In this research, we developed an Android-based application to evaluate activities have been carried out. We named this application EL-AKIP which is an android-based application for Grobogan Regency designed using web 2.0 and restful api using the RAD (Rapid Application Development) method. The use of Rapid Application Development (RAD), which is a software development process model that is incremental, especially for short processing times. Application testing uses the black box testing method where the results show that the application passes the test and is feasible to use
STUDENTS’ PERCEPTION TOWARDS THE ROLE OF ICE BREAKING ACTIVITIES IN LEARNING ENGLISH AT SENIOR HIGH SCHOOL
Authors: Al Ghifarah Naila , Pusparini Ririn
Published: August 2023

One of many factors that can influence students' feelings while learning English is a teacher's method or style of instruction that is not precise or monotonous. A fun and attractive learning environment can help students focus better and become more motivated to learn. Applying learning strategies suitable to students' conditions is one solution for increasing students'' motivation. For instance, the "ice-breaking" activity. Moreover, this research uses a qualitative approach to achieve the purposes of the research. The participants of this study were 30 students in a particular Islamic senior high school in Sidoarjo. This study used questionnaire, interview, and observation as research instruments. The study's findings indicate that students have a positive perception towards the role of ice breaking activities in learning English at senior high school. Ice-breaking is an effective strategy for increasing student motivation. Moreover, it has the potential to encourage students to learn. So that the classroom atmosphere becomes enjoyable and students' understanding of the subject matter improves.
ANTI-RACISM DISCOURSE IN TOI MOI SONG
Authors: Tiwiyanti Leni , Zaimar Yuli Sofiani , Passandaran Yosi M
Published: August 2023

Songs are typically composed for certain goals, messages, and audiences, and occasionally they are produced with particular listeners in mind. Common subjects in song lyrics include societal and current issues and challenges, with which the artist tries to communicate through manifestations of his or her beliefs, feelings, and ideologies. Therefore, language research to song lyrics is indeed very interesting to do, because it examines meaning. This research is interested in researching a song lyric entitled Toi Moi by Kids United. The researchers are interested in examining the anti-racism contained in it. The method in this research is qualitative and descriptive. This research uses van Dijk's critical discourse analysis theory, with elements of macro structure, super structure and micro structure. After that, the researchers would like to see the representation in this song. After deeper analysis, researchers found different meanings The result of the research is that not everything that is stated in a text will be the same as what is implied. Indeed, when we analyze macro structure, we interpreted, this song talks about a unity about two person or lovers. However, after researching deeper, by analyzing superstructure and micro structure the researchers found that the deeper meaning behind this song lyric is about racism and not about love story between two lovers. So, discourse analysis can be applied to analyze the deep meaning in a text.
Pelatihan Perakitan Battery Pack Lithium Ion 18650 Untuk Guru SMK di Kabupaten Jember
Authors: Karimah Cahyaning Nur , Suranto Dwi Djoko , Tyagita Dicky Adi , Zain Alex Taufiqurrohman , Pratama Aditya Wahyu , Sulistiono Dety Oktavia , Azhar Faruq Avero
Published: August 2023

The battery pack is one of the potential parts to be developed on a laboratory scale. The battery pack is a unit of several rechargeable battery cells assembled in series-parallel. Battery packs are generally equipped with a Battery management system (BMS). BMS is an electronic circuit that functions to limit the current and voltage entering the battery in the charging process when the battery is full. This will certainly prevent short circuits and increase battery life. As one of the vocational education institutions, SMK are expected to be able to read and take advantage of existing opportunities related to the increasing number of national vehicles and the acceleration of battery-based electric vehicles according to Presidential Regulation number 5 of 2019. In line with the link and match agenda of vocational universities with SMK, this community service team took the initiative to collaborate with SMK together with PTV as a facilitator and SMK teachers as SMK partners. This training activity begins with preparing an electric vehicle battery pack prototype and testing it in the automotive engine laboratory, engineering drawing and computing studio and DUDI partner workshops. At the end of the training, an evaluation was carried out in the form of a questionnaire on the success of the battery assembly training activities using a linkert scale. As a result, the battery assembly training which activities are measuring and monitoring battery pack, increase the knowledge of teachers about how to assemble 18650 lithium ion batteries according to the requirements of the motor that is used.