bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular circuitry of T-cell Development and Leukemogenesis
Authors: Tousinas Georgios , Tracy Melissa , Arnovitz Stephen , Friedman David J , Emmanuel Akinola Olumide , Khazaie Khashayarsha , Gounari Fotini 
Published: August 2023

Abstract
T-cell Acute lymphoblastic leukemia (T-ALL) is an aggressive disease with only a 10% 5-year survival rate for patients over 60, due to genomic instability. We have shown that β-catenin and TCF-1 cooperate in DP thymocytes to promote genomic instability leading to lymphomagenesis. We have also established that TCF-1 and HEB cooperate in the DP stage. Now, we aim to determine the molecular underpinnings of T-ALL and thymic development, by elucidating the interplay of all three factors, β-catenin, TCF-1, and HEB.
Aberrant activation of β-catenin promotes the development of Lymphoma/Leukemia equivalent to the human disease T-ALL and blocks thymocyte development in the early DP stage. Ablation of TCF-1 in thymocytes with activated β-catenin rescues from lymphomagenesis, but the developmental block persists. Antithetically, developmental progression is achieved only when HEB is conditionally knocked out. In an effort to explain this phenomenon, we found that genes associated with the transition of DP thymocytes from DPsmall to CD69+ are downregulated by activating β-catenin (e.g. Runx-3, Ccr-7, TOX-2, etc.) and revert upon deletion of HEB.
This is associated with changes in the binding of TCF-1 to DNA. Genomic sites that acquire TCF-1 binding upon β-catenin activation forfeit this binding when HEB is deleted, while at the same time novel TCF-1 binding sites emerge. These new binding sites are significantly more enriched for the conserved TCF-1 motif than TCF-1-bound sites in WT thymocytes. This observation promotes the notion that HEB guides TCF-1 towards alternative binding sites, thus altering gene expression.
These findings highlight the complex interactive relationship of TCF-1 and HEB in both normal development and disease.
NIH/NIAID R01 AI147652-01A1
Distal inflammatory priming of normal mammary tissue by the gut microbiome drives breast tumor metastasis via metabolic dysregulation
Authors: Putelo Audrey Marie , Feng Tzu-Yu , Kolli Sree , McGinty Mitchell , Rutkowski Melanie 
Published: August 2023

Abstract
Hormone receptor-positive (HR+), HER2− is the most prevalent metastatic breast cancer subtype, constituting 73.1% of the metastatic disease population in the US. Despite targeted therapies that have increased long-term survival, many patients develop and eventually succumb to metastatic disease. Tumor dissemination occurs early during disease progression and is driven by cellular and molecular changes in the tissue. Though host-intrinsic factors that preferentially predispose certain individuals to metastatic disease are poorly defined, gut microbial health has become increasingly recognized as a determinant of the metastatic potential of breast tumors. We demonstrated that commensal dysbiosis, an inflammatory gut microbiome with low biodiversity, drives HR+ tumor metastasis. Our work identified that a dysbiosis-induced CCL2/mast cell axis in normal (non-tumor-bearing) mammary tissues acts as a master regulator of early metastasis. Our present goal is to define how gut dysbiosis triggers tissue inflammation. We present evidence that dysbiosis-induced metabolic dysregulation increases early dissemination of HR+ tumors by initiating cellular and molecular changes in normal mammary tissue. Dysbiosis results in systemic insulin-glucose dynamics that resemble an insulin resistant phenotype. Additionally, we find that acylcarnitine species, byproducts of incomplete fatty acid β-oxidation which we hypothesize promote local tissue inflammation, accumulate in normal mammary tissues of dysbiotic mice. Altogether, we propose that commensal dysbiosis triggers a systemic metabolic shift that enhances the metastatic potential of HR+ tumors by shaping the immune landscape of the pre-cancerous mammary tissues.
Supported by grants from NIH (1RO1 CA253285, 2T32AI007496-26A1)
Accelerated tumorigenesis in a colorectal cancer model in Siglec-E knockout mice
Authors: Maniaci Brandon Lee , Friedman David J , Crotts Sydney B , Rajcula Matthew , Hammer Brady , Mai Elissa , Shapiro Virginia 
Published: August 2023

Abstract
The lifetime risk for colorectal cancer in the United States is approximately 4%. Individuals with Inflammatory Bowel Disease, including Ulcerative Colitis and Crohn’s Disease, have a substantially increased risk of developing colorectal cancer. The mechanisms for accelerated tumorigenesis due to enhanced inflammation are not fully characterized. Siglecs (sialic acid immunoglobulin lectin-like proteins) are a family of inhibitory receptors that are negative regulators of the immune response. Siglec-E is an inhibitory receptor that is expressed by innate immune cells, including monocytes, macrophages, neutrophils and dendritic cells. Interestingly, mice deficient in Siglec-E have accelerated development of tumors and reduced survival in a spontaneous mouse model of colorectal cancer (TS4-cre LSL-KRasG12D APClox468/wt). While tumors develop at approximately six months in mice with Siglec-E, tumors develop at approximately two months in Siglec-E knockout mice. Initial results indicate that Siglec-E knockout mice also have accelerated gut inflammation using the DSS colitis model as compared to WT mice. Current studies are examining inflammation that develops during tumorigenesis in Siglec-E knockout mice.
Center for Biomedical Discovery NIH R01 CA243545-01A1 to VSS Mayo Clinic Graduate School of Biomedical Sciences Deans fellowship: Initiative for maximizing student development (IMSD) R25 GM055252-26 Doyon Foundation
Ultrahigh-plex Spatial Phenotyping of the Glioblastoma Multiforme Immune Microenvironment
Authors: Klymyshyn Dmytro , Jhaveri Niyati , Prater Michael , Basu Subham , Kassim Yasmin , Ben Cheikh Bassem , Black Keith L , Sun Tao , Braubach Oliver 
Published: August 2023

Abstract
The glioblastoma multiforme (GBM) microenvironment is highly immunosuppressive, leading to poor clinical outcomes and median survival of less than 15 months. Information about the nature of immunosuppressive and immunostimulatory cell types in GBM is fragmented, and a better understanding is urgently needed. We have developed a spatial phenotyping application that permits comprehensive characterization of the human GBM immune microenvironment. The Phenocycler-Fusion is a fast spatial biology solution that affords ultrahigh-plex single-cell spatial readouts. We used this solution for deep immune phenotyping of &gt;50 proteins, comprising immune cell lineages, activation states and checkpoints, as well as markers for tumor, vascular and neuronal landscapes of GBM. Via single cell spatial phenotyping, we then isolated spatial signatures within the GBM tissue immune microenvironment. We focused on large numbers of glioma-associated macrophages that were identified via the combinatorial expression of key markers CD68, CD163, STAT1, STAT6, Iba-1 and SIRPα. The macrophages and their biomarker expression profiles displayed significant inter- and intra-tumoral heterogeneity, indicative of the complex biology of GBM. In addition, we profiled other immunosuppressive elements, including Tregs and exhausted T cells. Our data provide a comprehensive account of diverse immune cell populations in GBM and they may uncover systematic differences among GBM patient samples. Our application has enormous potential to further our understanding of the GBM immune microenvironment and is ready to be deployed by other laboratories.
The impact of the complement receptors C3aR1 and C5aR1 on the progression of melanoma
Authors: Oncul Selin , Cho Min Soon , Lee Hani , Carlos-Alcalde Wendolyn E , Singh Shailbala , Yee Cassian , Afshar-Kharghan Vahid 
Published: August 2023

Abstract
Melanoma is an aggressive skin cancer that develops from the malignant transformation of pigment-producing skin cells, melanocytes. The incidence of cutaneous melanoma is remarkably high, with an estimated number of new cases in the United States in 2022 close to 100,000 patients. Several previous reports pointed out the effect of the complement system in the progression of melanoma, although the precise mechanism is largely unknown. The complement system is a crucial component of innate immunity, and it also has a significant role in adaptive immunity regulating the function of immune cells. The complement receptors C3aR1 and C5aR1 are present on the surface of various immune cells. Anaphylatoxins (C3a and C5a) generated by complement activation bind to their respective receptors, C3aR1 and C5aR1, suppress the antitumor function of immune cells and promote migration and activity of immunosuppressive cells in the tumor microenvironment. Hence, C3aR1 and C5aR1 act as immune checkpoint receptors. To identify the precise role of the complement receptors in melanoma, we challenged C3−/−, C3aR1−/−, and C5aR1−/− mice with the B16F10 murine melanoma cells. We showed that the deficiency of these molecules substantially delayed tumor growth and promoted an antitumorigenic immune response. The results of this study indicate the distinct role of complement receptor signaling on melanoma growth and suggest a novel immunotherapeutic approach.
Developmental Research Program Award from the MD Anderson Melanoma SPORE (P50CA221703-04)
A membrane-associated inhibitory axis of MHC-I presentation for cancer immune evasion
Authors: Lu Qiao , Chen Xufeng , Zhou Hua , Liu Jia , Nadorp Bettina , Lasry Audrey , Sun Zhengxi , Zhang Jiangyan , Cammer Michael , Wang Kun , Ciantra Zoe , You Jia , Guo Qianjin , Zhang Hongbing , Sengupta Debrup , Boukhris Ahmad , Liu Cheng , Cresswell Peter , Dahia Patricia L M , Aifantis Iannis , Wang Jun 
Published: August 2023

Abstract
Although the success of immune-checkpoint blockade has revolutionized cancer treatment, a number of tumors do not respond or develop resistance, including acute myeloid leukemia (AML). A potential mode of resistance is immune evasion of T-cell immunity involving aberrant MHC-I antigen presentation (AP). To map such mechanisms of resistance we identified key AP regulators using specific peptide-MHC-I-guided CRISPR/Cas9 screens in AML. The top-ranked negative regulators were surface protein Sushi Domain Containing 6 (SUSD6), Transmembrane Protein 127 (TMEM127), and the E3 ubiquitin ligase WWP2. SUSD6 is abundantly-expressed in AML and multiple solid cancers, ablation of which profoundly enhanced AP and reduced tumor growth in CD8+ T cell-dependent manner. Mechanistically, SUSD6 forms a molecular complex with TMEM127 and MHC-I, recruiting WWP2 for MHC-I lysosomal degradation. Together with the SUSD6-TMEM127-WWP2 gene signature negatively-correlated with cancer survival, our findings define a membrane-associated AP inhibitory axis as broadly-applicable therapeutic targets for both leukemia and solid cancers.
This work is supported by the Mark Foundation ASPIRE Award to J.W. I.A. is supported by the NIH (NCI and NHLBI) (R01CA216421, R01 CA173636, 1R01CA228135, R01CA242020, 1R01HL159175), the Vogelstein Foundation and the Evans MDS Foundation. J.W. is supported by the NIH (R37CA273333-01, R21AI163924-02). Q.L. is supported by the Cancer Research Institute Irvington Postdoctoral Fellowship.
In vivo immune inhibitory role of Ly-6A protein
Authors: Bamezai Anil K , Rathbun Luke , Buzinkai Noah , Pasquale Olivia , Morrissey Amanda , Brayer Mallory , Magahis Angela , Ngo Gina , Tillinghast Christina , Bisaccia Beverly , Capozzoli Benjamin 
Published: August 2023

Abstract
Ly-6A is a GPI-anchored cell surface protein with reported cell adhesion and cell signaling role in CD4+ T cells. Ly-6A shows low expression on naïve T cells; however, its expression is elevated upon T cell activation. Additionally, IFN-γ and IL-27 cytokines increase Ly-6A expression, a feature observed in immune checkpoint inhibitory (ICI) proteins, such as PD-1 and CTLA-4. Many reports using cell lines and primary cells show, as for ICI proteins, Ly-6A expression inhibiting clonal expansion of antigen receptor-stimulated CD4+ T cells. While the published in vitro and ex vivo studies provide strong evidence for Ly-6A as T cell inhibitory protein, in vivo role of Ly-6A is unknown. Using a tumor transplantation mouse model, we have found that Ly-6A-deficient mice support slower or no growth of B16-F10 melanoma and MC38 adenocarcinoma tumors compared to the wildtype C57BL/6 control mice. We report that Ly-6A-deficient mice injected with B16-F10 tumor cells have elevated number of activated T cells in the draining lymph nodes (DLN) on day-3 post-injection. Furthermore, significantly elevated proliferation of DLN cells from B16-F10 injected Ly-6A-deficient mice was observed on day-7, as assessed by ex vivo proliferation assays. Transcriptome analyses of the tumor tissues showed, among others, significantly elevated expression of IFN-γ inducible and chemokine genes. Additionally, CD73 expression, as assessed by confocal microscopy, was lower in B16-F10 tumor tissues from Ly-6A-deficient mice than the wildtype tumors. Our results reveal a novel immune inhibitory role of Ly-6A protein and potential ICI target for cancer immunotherapy, either as a standalone or combinatorial ICI blockade strategy.
Supported by funds from Department of Biology, Villanova University (SRG) & Sigma Xi
Surgical Morbidity of Laparoscopic Hysterectomy versus Abdominal Hysterectomy: A Retrospective Overview
Authors: Agarwal Mukta , Sinha Shivangni , Singh Smita , Haripriya H. , Roy Ishita 
Published: August 2023

Objectives:
Laparoscopic skills are not an innate behavior, nor can they be easily mimicked, and can only be acquired through hands-on training. The need for reliable training and its assessment is becoming increasingly important with the course of time.

Materials and Methods:
A retrospective comparative study was done in a tertiary care center where all patients undergoing hysterectomy by laparoscopic and abdominal route were included in the study.

Objectives:
Our study aims to compare the operative and postoperative complications of laparoscopic hysterectomy with abdominal hysterectomy. The study was conducted from June 2016 to October 2022.

Results:
The mean operative time for uteri size lesser than 12 weeks was found significant in the total laparoscopic hysterectomy (TLH) group (75 ± 25 min) to total abdominal hysterectomy (TAH) (117 ± 28 min, P < 0.001). The mean blood loss in the TLH group was significant (110 ± 30 ml vs. 160 ± 116 ml, P < 0.002). The mean hospital stay was significantly shorter in TLH (4 ± 2.4 days vs. 7 ± 2.41 days, P < 0.002). The operative and postoperative complications observed were 3.1% in the TLH group and 11.7% in the TAH group.

Conclusion:
TLH when performed efficiently has proved to be a preferable route over other conventional hysterectomies.
Socio-economic, education, and insurance-related factors associated with the treatment completion rates in patients with nonmetastatic urinary bladder cancer: A Retrospective cohort study
Authors: Rohith Gorrepati , Gaur Abhay Singh , Nayak Prasant , Mandal Swarnendu , Das Manoj K. , Kumaraswamy Santosh , Tarigopula Vivek , Tripathy Sambit 
Published: August 2023

Introduction:
Among urological malignancies, the diagnosis and treatment of urinary bladder cancer (UBC) incurs the highest cost per patient. Our objective was to broaden the current understanding of how demographic, socioeconomic, education, and insurance-related factors influence UBC management.

Methods:
Between January 2017 and December 2019, all patients with nonmetastatic bladder cancer were included. The demographic, treatment, and follow-up details were retrieved from a prospectively maintained database, and the Modified Kuppuswamy Index was used to evaluate the patients’ socioeconomic level. Patients were divided into the completed treatment group, or the incomplete treatment group based on adherence to the initially intended treatment plan. Patients who presented with benign disease or metastases were not included.

Results:
Eighty-nine patients did not complete the initially intended course of treatment out of 132 patients who needed additional management after the initial transurethral resection. Comparable risk factors and demographic profiles existed in both groups. Patients with intermediate-risk disease are more likely to fail to adhere to the initial intended treatment (odds ratio [OR] = 0.09; 95% confidence interval [CI]: 0.02–0.30). On logistic regression analysis, upper socioeconomic status (OR = 6.8; 95% CI: 0.35–132.1) patients and patients with higher educational status of graduation or above (OR = 3.62; 95% CI: 0.75–17.43) had higher chances of treatment completion. Education status significantly impacted treatment completion on multivariate analysis (P = 0.01). Patients who utilized employer-funded insurance had better treatment compliance (OR = 4.1; 95% CI: 0.90–18.7). The compliance was unaffected by smoking, occupation, or other demographic factors.

Conclusion:
Patients with low economic status, low levels of education, and who need adjuvant intravesical therapy had considerably greater treatment dropout rates.
Low-intensity extracorporeal shockwave therapy for Peyronie’s disease: An Indian experience
Authors: Maiti Krishnendu , Srivastava Swadeep Kumar , Pal Dilip Kumar 
Published: August 2023

Introduction:
Efficacy of low-intensity extracorporeal shockwave therapy (LiESWT) in Peyronie’s disease (PD) has not been studied in an Indian population. Here, we studied the effect of LiESWT in Indian PD patients.

Methods:
This prospective study was conducted on 25 patients who completed weekly sessions of LiESWT for 6 weeks with a follow-up of 6 months. Patients were evaluated using International Index of Erectile Function (IIEF)-5 questionnaire for erectile dysfunction and visual analog scale for pain. Baseline and follow-up examinations included measurement of plaque size and curvature. The primary outcome was to assess remission of pain and reduction of plaque size along with improvement of penile curvature and erectile function as the secondary outcome.

Results:
Primary goal of pain reduction and ≥50% reduction of plaque size was achieved in 64% and 20% of patients, respectively. Improvement in vaginal penetration during sexual intercourse and IIEF-5 score increase of ≥3 was achieved 20% and 36% cases, respectively. The mean reduction of penile curvature was more with plaque calcification (PC), but the difference was not statistically significant (P = 0.26). The difference in mean visual analog scale reduction was more in noncalcified plaque (P = 0.002). The mean reduction of plaque size in patients with PC was significant (P = 0.03).

Conclusions:
Shockwave therapy is a probable alternative treatment option. A significant improvement was observed in pain and plaque size in patients treated by LiESWT. The presence of PC may affect the outcome of LiESWT in PD.
EphrinB2: Expression of a novel potential target in renal cell carcinoma
Authors: Gupta Chhavi , Sali Akash Pramod , Jackovich Alexandra , Ma Binyun , Sadeghi Sarmad , Quinn David , Gill Parkash , Gill Inderbir 
Published: August 2023

Introduction:
Renal cell carcinoma (RCC) is primarily managed by surgery with the use of systemic targeted therapy in a metastatic setting. Newer targeted therapeutic options are evolving; Eph-ephrin is a potential new pathway. The therapeutic potential of targeting the EphB4-EphrinB2 pathway has been demonstrated in many solid tumors; however, its expression in RCC has only been evaluated in a few studies with limited cases. We herein determine the immunohistochemical expression of EphrinB2 in RCC.

Methods:
A tissue microarray comprising 110 cases of different histological subtypes of RCC and 10 normal kidney tissues were stained with monoclonal anti-EphrinB2 antibody (Abcam, AB201512). The tumor and endothelial cells expressing the EphrinB2 were examined and its expression was correlated with sex, histological subtypes, and tumor nodes metastasis (TNM) stage.

Results:
Twenty cases of urothelial carcinoma and two unsatisfactory conventional clear cell RCC cases were excluded, and EphrinB2 expression was interpreted in the remaining 88 tumors. EphrinB2 was expressed in 42 out of 88 tumors (47.7%) and was negative in the normal renal parenchyma. There was a statistically significant difference in the expression of EphrinB2 in males (55%) and females (32%). However, no such difference of expression was noted for the histological subtypes and the stages. Half (51%) of Stage 1 (n = 30) and Stage 2 (n = 11) tumors showed EphrinB2 positivity.

Conclusions:
EphrinB2 is expressed in approximately half of RCC cases. EphrinB2 expression in the early stage cancer might indicate its induction as an early event.
Comparison of standing, side bending and awake supine manual traction dynamic radiographs for predicting spinal flexibility with postoperative correction rate in adolescent idiopathic scoliosis
Authors: Subramaniam Macherla Haribabu , Venkatesan Muralidharan , Hegde Sajan K 
Published: August 2023

Abstract

Background:
The aim of the study was to compare awake supine manual traction radiograph with standing side bending radiograph in adolescent idiopathic scoliosis (AIS) patients and to analyze, which one among them is the best predictor of spinal flexibility index in varying degrees of AIS curves with minimal to severe Cobb angle.

Materials and Methods:
AIS patients, who underwent surgery during the period from 2015 to 2018, were retrospectively analyzed. Supine manual traction anteroposterior radiograph were taken with the patient in the supine position, with traction applied by a person with the head halter at the chin and counter traction applied with pelvic belt, leg straps. Patients were divided into three groups A, B, and C based on Cobb angle of the major structural curve. Patients with Cobb angles between 40° to 65°, 65° to 90°, and more than 90° were included in Groups A, B, and C, respectively. Flexibility indices obtained from both traction and bending radiographs were correlated with percent change in Cobb angle correction post-surgery. Statistical analysis was done to find Pearson correlation coefficient (r) between variables and results were tabulated.

Results:
There were 36, 16, and 16 patients in Group A, B, and C, respectively. The mean age of the cohort was 13.38 years. Group A had a positive correlation to traction radiographs (r = + 0.188, P = 0.455). Group B had a statistically significant positive correlation to bending radiographs (r = + 0.729, P = 0.04). A statistically significant positive correlation with traction radiographs (r = + 0.769, P = 0.016) was seen in Group C.

Conclusion:
Awake supine manual traction radiographs reveal better flexibility index in severe stiff (Cobb more than 90°) curves. In moderately stiffer curves (Cobb 65°–90°) standing side bending radiographs provide a better flexibility index than traction radiographs. Supine manual traction radiographs should always accompany bending radiographs in evaluating AIS patients, especially with severe stiff curves.