Surgical Treatment of Proximal Humerus Unicameral Bone Cyst: A Case Report.

Unicameral bone cysts (UBCs) are noncancerous, fluid-containing sacs commonly seen in the metaphysis of long bones among young individuals, mainly affecting the proximal humerus and femur. Since they are painless, 80% of patients do not experience any symptoms from UBCs unless it is complicated by a pathological or stress fracture. These patients usually present with no history of trauma, with mild pain, local tenderness, and occasionally swelling. The diagnosis of UBCS can either be an incidental finding or can be made with the help of clinical features, radiographs, and differential diagnoses of UBCs like aneurysmal bone cyst, fibrous dysplasia, enchondroma, eosinophilic granuloma, and intraosseous ganglia can be ruled out. While identifying these cysts is often straightforward, there is ongoing debate regarding the optimal management approach. We report a case of a 16-year-old female with proximal humerus UBC who presented with a pathological fracture of the right proximal humerus. The patient was initially managed conservatively. However, she sustained a refracture at the same site twice over four years. Due to fracture recurrence and residual deformity, it was treated surgically with curettage, bone grafting, and internal fixation. The normal alignment and function of the right upper limb were restored postoperatively.

Enhancing Wheat Tolerance to Cadmium Stress through Moringa Leaf Extract Foliar Application.

Cadmium, a hazardous heavy metal prevalent in plants and soil, poses a significant threat to human health, particularly as approximately 60% of the global population consumes wheat, which can accumulate high levels of Cd through its roots. This uptake leads to the translocation of Cd to the shoots and grains, exacerbating the potential health risks. However, promising results have been observed with the use of moringa leaf extract (MLE) foliar spray in mitigating the adverse effects of Cd stress. The current experiment was conducted to find out the Cd stress tolerance of wheat varieties V1 = Akbar-19 and V2 = Dilkash-2020 under exogenous spray of MLE. The treatments of this study were T0 = 0% MLE + 0 µM Cd, T1 = 3% MLE + 0 µM Cd, T2 = 0% MLE + 400 µM Cd, and T3 = 3% MLE + 400 µM Cd. Cd stress demonstrated a significant reduction in morphological attributes as shoot and root fresh weight (22%), shoot and root dry weight (24.5%), shoot and root length (22.5%), area of leaf and number of leaves 30.5%, and photosynthetic attributes (69.8%) in comparison with control. Exposure of wheat plants to Cd toxicity cause oxidative stress, increased H2O2, and MDA up to 75% while foliar application of MLE reduced the activities of reactive oxygen species (ROS). The activity of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and ascorbic acid (AsA) increased up to 81.5% as well as organic osmolytes such as phenolics, total soluble proteins, and total soluble sugars were improved up to 77% by MLE applications under Cd stress. Higher accumulation of ionic contents root Na+ (22%) and Cd (44%) was documented in plants under Cd stress as compared to control, while uptake of root mineral ions Ca2+ and K+ was 35% more in MLE-treated plants. In crux, Cd toxicity significantly declined the growth, photosynthetic, and biochemical parameters while 3% MLE application was found effective in alleviating the Cd toxicity by improving growth and physiological parameters while declining reactive oxygen species and root Na+ as well as Cd uptake in wheat.

A Plasmacytoid Variant of Urothelial Carcinoma: A Rare Entity.

A rare histological variant of transitional cell urothelial carcinoma, the plasmacytoid variant, was recently included in the World Health Organization classification of urothelial tract tumors. This variant has a morphological resemblance to other tumors, which poses a diagnostic challenge for identifying this tumor and may often lead to misdiagnosis. Vigilant histopathological analysis and immunostaining are required to delineate the correct diagnosis. The plasmacytoid variant of urothelial carcinoma is an aggressive tumor with a poor prognosis, making correct diagnosis essential for early and appropriate treatment. This paper presents the case of a 46-year-old male with a plasmacytoid variant of high-grade urothelial carcinoma who underwent transurethral resection of a bladder tumor, received chemotherapy, and is currently undergoing follow-up.

The Spectrum of Echocardiographic Findings Across Stages I-V of Chronic Kidney Disease.

AIM AND BACKGROUND: Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. This study aimed to assess the frequency of cardiac abnormalities across different stages of CKD, providing insights into the relationship between renal dysfunction and cardiac abnormalities. MATERIAL AND METHODS: A cross-sectional observational study was conducted at Lahore General Hospital's Nephrology Department, enrolling 356 non-dialysis CKD patients (stages I-V) over one year. Participants aged 18-65 years with CKD duration of three months or more were included. Exclusion criteria encompassed dialysis dependency, transplantation, acute kidney injury, and various cardiac conditions. Detailed echocardiographic evaluation of cardiac structure and function was noted. RESULTS: This study included 356 patients with CKD across stages I-V, with the majority in stages III (44.7%) and IV (36.5%). Significant variations were observed in age (p<0.000), hypertension prevalence (p=0.004), and smoking status. Haemoglobin, calcium, and phosphate levels differed significantly across stages (p<0.001). Echocardiographic findings revealed significant differences: left ventricular hypertrophy frequency increased from 12.5% in stages I-II to 60.0% in stage V (p=0.001); diastolic dysfunction worsened, with grades 2-3 dysfunction increasing from 6.2% in stages I-II to 51.4% in stage V (p=0.000); systolic dysfunction increased with reduced ejection fraction (<45%) more common in advanced stages (p=0.000); global longitudinal strain worsened from -18.47% to -15.34% (p=0.000); left atrial volume index and pulmonary hypertension also increased significantly (p=0.049). CONCLUSION: This study demonstrates a significant correlation between the progression of CKD and the severity of echocardiographic abnormalities. As CKD advances, structural and functional cardiac abnormalities increase, underscoring the importance of early cardiac evaluation and intervention to improve cardiovascular outcomes in non-dialysis-dependent CKD patients.

Comprehensive pan-cancer analysis reveals VSIR as a candidate immunologic, diagnostic, and prognostic biomarker.

OBJECTIVES: Being a checkpoint, the expression level of V-set immunoregulatory receptor (VSIR) serves as an indicator of the extent of immunosuppression. Our objective was to undertake a pan-cancer analysis to examine the expression, genetic alterations, prognosis, and immunologic features associated with VSIR. METHODS: The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), GEPIA2, UALCAN, OncoDB, Human Protein Atlas (HPA), STRING, DAVID, cell culture, clinical sample collection, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used. RESULTS: This study comprehensively assessed VSIR across 33 cancers using TCGA and GTEx databases. Differential expression analysis revealed elevated VSIR in several cancers, notably in cholangiocarcinoma, esophageal carcinoma, kidney renal cell carcinoma, and liver hepatocellular carcinoma, while decreased expression was observed in various others. Prognostic analysis highlighted its significant association with reduced overall survival (OS) in ESCA and LIHC. Investigation into cancer stages demonstrated a correlation between VSIR expression and stage in ESCA and LIHC. Promoter methylation analysis indicated decreased VSIR methylation levels in tumors, implicating a role in oncogenesis. Furthermore, subcellular localization predictions, Tumor Mutational Burden (TMB), and Microsatellite Instability (MSI) correlations revealed intriguing insight into VSIR's function. Notably, a positive correlation was identified between VSIR expression and various immune cells in both cancers. Protein-protein interaction (PPI) network construction and gene enrichment analysis elucidated VSIR-associated dysregulated pathways, emphasizing its possible involvement in diverse pathways. Finally, experimental validation using LIHC clinical samples and cell lines confirmed elevated VSIR expression, supporting its oncogenic role. CONCLUSION: Collectively, these findings present a comprehensive understanding of VSIR's diverse roles and potential clinical implications in ESCA and LIHC.

Study of some graph theoretical parameters for the structures of anticancer drugs.

Eigenvalues have great importance in the field of mathematics, and their relevance extends beyond this area to include several other disciplines such as economics, chemistry, and numerous fields. According to our study, eigenvalues are utilized in chemistry to express a chemical compound's numerous physical properties as well as its energy form. It is important to get a comprehensive understanding of the interrelationship underlying mathematics and chemistry. The anti-bonding phase is correlated with positive eigenvalues, whereas the bonding level is connected with negative eigenvalues. Additionally, the non-bonded level corresponds to eigenvalues of zero. This study focuses on the analysis of various structures of anticancer drugs, specifically examining their characteristic polynomials, eigenvalues of the adjacency matrix, matching number and nullity. Consequently, the selected structures of the aforementioned anticancer drugs exhibit stability since they are composed of closed-shell molecules, characterized by a nullity value of zero.

Identification and validation of key genes in gastric cancer: insights from in silico analysis, clinical samples, and functional assays.

INTRODUCTION: The underlying mechanisms of gastric cancer (GC) remain unknown. Therefore, in this study, we employed a comprehensive approach, combining computational and experimental methods, to identify potential key genes and unveil the underlying pathogenesis and prognosis of GC. METHODS: Gene expression profiles from GEO databases (GSE118916, GSE79973, and GSE29272) were analyzed to identify DEGs between GC and normal tissues. A PPI network was constructed using STRING and Cytoscape, followed by hub gene identification with CytoHubba. Investigations included expression and promoter methylation analysis, survival modeling, mutational and miRNA analysis, gene enrichment, drug prediction, and in vitro assays for cellular behaviors. RESULTS: A total of 83 DEGs were identified in the three datasets, comprising 41 up-regulated genes and 42 down-regulated genes. Utilizing the degree and MCC methods, we identified four hub genes that were hypomethylated and up-regulated: COL1A1, COL1A2, COL3A1, and FN1. Subsequent validation of their expression and promoter methylation on clinical GC samples through targeted bisulfite sequencing and RT-qPCR analysis further confirmed the hypomethylation and overexpression of these genes in local GC patients. Furthermore, it was observed that these hub genes regulate tumor proliferation and metastasis in in vivo and exhibited mutations in GC patients. CONCLUSION: We found four potential diagnostic and prognostic biomarkers, including COL1A1, COL1A2, COL3A1, and FN1 that may be involved in the occurrence and progression of GC.

Story of 20 Years of Triumph: A Case Report of Two Patients With Stage IV Granulosa Cell Tumor of the Ovary.

Ovarian granulosa cell tumors (GCTs) are rare neoplasms with a unique incidence pattern peaking in postmenopausal women. This case report presents two instances of stage 4 recurrent adult GCTs with a prolonged 20-year follow-up. Patient 1, diagnosed at 54 years, experienced multiple recurrences managed through surgery, hormonal therapy, and chemotherapy, culminating in hepatocellular carcinoma. Patient 2, diagnosed at 67 years, underwent various treatments, including surgery, chemotherapy, and hormonal therapy, demonstrating disease stability. Despite the generally favorable prognosis, these cases highlight the challenges of managing recurrent GCTs, emphasizing the need for tailored therapeutic approaches.

Iron oxide nanoparticle (Fe3O4 NPs) synthesized from B. subtilis reduced arsenic (as) toxicity in rice (Oryza sativa L.) plant.

Arsenic (As) is one of the most important water pollutant of global concern due to its extreme hazard. In the present study, B. subtilis synthesized iron oxide nanoparticles (Fe3O4 NPs) were used for mitigation of harmful metalloid As from the aqueous solution. Initially, the arsenic removal efficiency was tested in a batch culture experiment across various concentrations (5, 10 and 15 ppm) of B. subtilis synthesized Fe3O4 NPs at different pH, time interval and agitation speed. Optimal removal efficiency of As by using B. subtilis synthesized Fe3O4 NPs was observed at pH 7, after 80 min, and with agitation at 200 rpm. Additionally, hydroponic culture experiment was designed to assess B. subtilis synthesized Fe3O4 NPs efficiency in removal of As from As-contaminated water used to irrigate rice plants. Results revealed that B. subtilis synthesized Fe3O4 NPs effectively removed As from the contiminated water and reduced its uptake by the different parts of rice plants (root, shoot and leaf). Furthermore, these B. subtilis synthesized Fe3O4 NPs also reduced the bioaccumulation and enhanced plant tolerance to As, suggesting their potential in mitigating heavy metal toxicity, especially As and promoting plant growth. Thus, this study proposes B. subtilis synthesized Fe3O4 NPs as nano-adsorbents in reducing arsenic toxicity in rice plants.

Diagnosis of Angioimmunoblastic T Cell Lymphoma After Receiving First Dose of Pfizer/BioNTech (BNT162b2) Vaccine: A Case Report.

Pfizer/BioNTech (BNT162b2) is a messenger RNA (mRNA) vaccine that is highly effective in preventing the most severe outcomes of COVID-19 infection. Nucleoside-modified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines induce effective stimulation of T follicular helper (TFH) cells, leading to a robust germinal center B cell response. Side effects from the BNT162b2 vaccination, including significant lymphadenopathy, have been reported previously. Here, we present a case of angioimmunoblastic lymphoma (AITL), a rare, peripheral T-cell lymphoma with RHOA-G17v-mutated gene developing in a patient following BNT162B2 vaccine with a plausible explanation. A 60-year-old Asian female received her first dose of Pfizer BNT162B2 mRNA vaccine in August 2021. Right after her vaccination, she developed right axillary lymphadenopathy. She received her second vaccine dose in September 2021. Thereafter, she developed lymph node (LN) enlargement in her neck and groin. She underwent left posterior cervical and left groin LN excisional biopsy in April 2022 due to persistent palpable lymphadenopathy. Biopsy results then demonstrated benign follicular hyperplasia. For progressive B symptoms, a right axillary LN biopsy was done, which demonstrated AITL, with molecular studies revealing mutation in TET-2, IDH-2, and RHOA-G17v genes. Progression of AITL following BNT162B2 mRNA vaccine is limited in literature. Our case demonstrates a plausible correlation between the diagnosis of AITL following mRNA vaccination due to the malignant transformation of the TFH cells in patients who have a predisposing mutation of RHOA-17v. Given the rarity of AITL and the heterogeneity of molecular findings, more studies are needed to establish such an association.

Understanding effective post-test linkage strategies for HIV prevention and care: a scoping review.

INTRODUCTION: Following HIV testing services (HTS), the World Health Organization recommends prompt linkage to prevention and treatment. Scale-up of effective linkage strategies is essential to achieving the global 95-95-95 goals for maintaining low HIV incidence by 2030 and reducing HIV-related morbidity and mortality. Whereas linkage to care including same-day antiretroviral therapy (ART) initiation for all people with HIV is now routinely implemented in testing programmes, linkage to HIV prevention interventions including behavioural or biomedical strategies, for HIV-negative individuals remains sub-optimal. This review aims to evaluate effective post-HTS linkage strategies for HIV overall, and highlight gaps specifically in linkage to prevention. METHODS: Using the five-step Arksey and O'Malley framework, we conducted a scoping review searching existing published and grey literature. We searched PubMed, Cochrane Library, CINAHL, Web of Science and EMBASE databases for English-language studies published between 1 January 2010 and 30 November 2023. Linkage interventions included as streamlined interventions-involving same-day HIV testing, ART initiation and point-of-care CD4 cell count/viral load, case management-involving linkage coordinators developing personalized HIV care and risk reduction plans, incentives-financial and non-financial, partner services-including contact tracing, virtual-like social media, quality improvement-like use of score cards, and peer-based interventions. Outcomes of interest were linkage to any form of HIV prevention and/or care including ART initiation. RESULTS: Of 2358 articles screened, 66 research studies met the inclusion criteria. Only nine linkage to prevention studies were identified (n = 9/66, 14%)-involving pre-exposure prophylaxis, voluntary medical male circumcision, sexually transmitted infection and cervical cancer screening. Linkage to care studies (n = 57/66, 86%) focused on streamlined interventions in the general population and on case management among key populations. DISCUSSION: Despite a wide range of HIV prevention interventions available, there was a dearth of literature on HIV prevention programmes and on the use of messaging on treatment as prevention strategy. Linkage to care studies were comparatively numerous except those evaluating virtual interventions, incentives and quality improvement. CONCLUSIONS: The findings give insights into linkage strategies but more understanding of how to provide these effectively for maximum prevention impact is needed.

Anaplastic Large Cell Lymphoma (ALCL) With a Sarcomatoid Variant Presenting As Distributive Shock in a 41-Year-Old Female: A Case Report.

The sarcomatoid variant is considered a rare subtype of anaplastic large cell lymphoma. We present a 40-year-old diabetic female who was evaluated in the ER for distributive shock, requiring vasopressors and mechanical ventilation. An extensive workup was negative for infection. A serial CT scan of the abdomen and pelvis showed evolving lymphadenopathy, and a biopsy revealed malignant anaplastic lymphoma cells with a sarcomatous variant. The oncology team recommended the initiation of inpatient chemotherapy; however, the family opted to proceed with comfort care measures.

Identifying and validating MMP family members (MMP2, MMP9, MMP12, and MMP16) as therapeutic targets and biomarkers in kidney renal clear cell carcinoma (KIRC).

Kidney Renal Clear Cell Carcinoma (KIRC) is a malignant tumor that carries a substantial risk of morbidity and mortality. The MMP family assumes a crucial role in tumor invasion and metastasis. This study aimed to uncover the mechanistic relevance of the MMP gene family as a therapeutic target and diagnostic biomarker in Kidney Renal Clear Cell Carcinoma (KIRC) through a comprehensive approach encompassing both computational and molecular analyses. STRING, Cytoscape, UALCAN, GEPIA, OncoDB, HPA, cBioPortal, GSEA, TIMER, ENCORI, DrugBank, targeted bisulfite sequencing (bisulfite-seq), conventional PCR, Sanger sequencing, and RT-qPCR based analyses were used in the present study to analyze MMP gene family members to accurately determine a few hub genes that can be utilized as both therapeutic targets and diagnostic biomarkers for KIRC. By performing STRING and Cytohubba analyses of the 24 MMP gene family members, MMP2 (matrix metallopeptidase 2), MMP9 (matrix metallopeptidase 9), MMP12 (matrix metallopeptidase 12), and MMP16 (matrix metallopeptidase 16) genes were denoted as hub genes having highest degree scores. After analyzing MMP2, MMP9, MMP12, and MMP16 via various TCGA databases and RT-qPCR technique across clinical samples and KIRC cell lines, interestingly, all these hub genes were found significantly overexpressed at mRNA and protein levels in KIRC samples relative to controls. The notable effect of the up-regulated MMP2, MMP9, MMP12, and MMP16 was also documented on the overall survival (OS) of the KIRC patients. Moreover, targeted bisulfite-sequencing (bisulfite-seq) analysis revealed that promoter hypomethylation pattern was associated with up-regulation of hub genes (MMP2, MMP9, MMP12, and MMP16). In addition to this, hub genes were involved in various diverse oncogenic pathways. The MMP gene family members (MMP2, MMP9, MMP12, and MMP16) may serve as therapeutic targets and prognostic biomarkers in KIRC.

Exploring the Diagnostic and Prognostic Predictive Values of Ferroptosis- Related Markers in Lung Adenocarcinoma.

BACKGROUND: Lung Adenocarcinoma (LUAD), a common and aggressive form of lung cancer, poses significant treatment challenges due to its low survival rates. AIM: To better understand the role of ferroptosis driver genes in LUAD, this study aimed to explore their diagnostic and prognostic significance, as well as their impact on treatment approaches and tumor immune function in LUAD. METHOD: To accomplish the defined goals, a comprehensive methodology incorporating both in silico and wet lab experiments was employed. A comprehensive analysis was conducted on a total of 233 ferroptosis driver genes obtained from the FerrDB database. Utilizing various TCGA databases and the RT-qPCR technique, the expression profiles of 233 genes were examined. Among them, TP53, KRAS, PTEN, and HRAS were identified as hub genes with significant differential expression. Notably, TP53, KRAS, and HRAS exhibited substantial up-regulation, while PTEN demonstrated significant down-regulation at both the mRNA and protein levels in LUAD samples. The dysregulation of hub genes was further associated with poor overall survival in LUAD patients. Additionally, targeted bisulfite-sequencing (bisulfite-seq) analysis revealed aberrant promoter methylation patterns linked to the dysregulation of hub genes. RESULT & DISCUSSION: Furthermore, hub genes were found to participate in diverse oncogenic pathways, highlighting their involvement in LUAD tumorigenesis. By leveraging the diagnostic and prognostic potential of ferroptosis driver hub genes (TP53, KRAS, PTEN, and HRAS), significant advancements can be made in the understanding and management of LUAD pathogenesis. CONCLUSION: Therapeutic targeting of these genes using specific drugs holds great promise for revolutionizing drug discovery and improving the overall survival of LUAD patients.

Bone morphogenetic protein 1: a prognostic indicator and potential biomarker in three cancer types.

BACKGROUND: Bone morphogenetic protein 1 (BMP1) is a metalloprotease that plays a role in activating both transforming growth factor-ß (TGF-ß) and BMP signaling pathways. TGF-ß has been identified as a factor initiating and facilitating cancer development. Consequently, we propose the hypothesis that dysregulation of BMP1 could potentially contribute to the onset and advancement of human cancers. METHODS: In this research, we aimed to analyze BMP1 expression level and the associated clinical outcomes across various cancers using online cancer OMICS databases, advanced Bioinformatics tools, and molecular analyses. RESULTS: The outcomes of our web server-based expression analysis indicated an up-regulation of BMP1 in a majority of the human cancers examined. External validation using clinical samples also showed higher expression of BMP1. Moreover, heightened BMP1 expression exhibited a noteworthy correlation with reduced overall survival (OS) duration in Bladder Cancer (BLCA), Kidney Renal Clear Cell Carcinoma (KIRC), and Lung Adenocarcinoma (LUAD) patients. This suggests a substantial involvement of the BMP1 gene in the development and progression of these three types of cancers. The major signaling pathways related with BMP1 enriched genes were "ECM-receptor interaction, Amoebiasis, Focal adhesion, Protein digestion and absorption, progesterone-mediated, PI3K-Akt signaling pathway, and platelet activation". Moreover, we also explored some interesting correlations among BMP1 expression and its DNA promoter methylation level, CD8+ T immune cells level, and genetic variations. CONCLUSION: In conclusion, our study has provided some solid basis for BMP1 to be used as a reliable common biomarker for BLCA, KIRC, and LUAD patients.

Comparison of the Efficacy of Two-Week Vonoprazan Versus Lansoprazole-Based Quadruple Sequential Antibiotic Therapy in Eradicating Helicobacter pylori Infection: A Non-randomized Clinical Trial.

AIM: The prevalence of Helicobacter pylori is escalating in developing countries, exacerbated by unjustified antibiotic usage, which leads to increased resistance. This trend has been notably amplified since the COVID-19 pandemic. Consequently, the effectiveness of existing eradication regimens has been compromised. This study aimed to compare the efficacy of two weeks of vonoprazan-based quadruple sequential therapy and lansoprazole-based quadruple sequential therapy in treating H. pylori infection.  Methods: A non-randomized clinical trial was conducted over 18 months at the Department of Gastroenterology, Lahore General Hospital, Lahore, Pakistan. It included patients presenting with dyspepsia, as defined by the Rome IV criteria, and who tested positive on the urea breath test. Patients were divided into two groups, i.e., Group A and Group B. Group A patients received lansoprazole 30 mg + amoxicillin + tinidazole + tab. colloidal bismuth subcitrate for the first seven days, followed by lansoprazole + levofloxacin + azithromycin + colloidal bismuth subcitrate. Group B patients received vonoprazan + amoxicillin + tinidazole + colloidal bismuth subcitrate for the first seven days, followed by vonoprazan + levofloxacin + azithromycin + colloidal bismuth subcitrate. Both regimes continued for 14 days. Four weeks after 14 days of the treatment, an early morning urea breath test was conducted to evaluate the efficacy of the treatment. Patients were scheduled for follow-up visits at seven and 14 days post-treatment initiation to record adverse events and assess compliance with the treatment regimen. Patients who lost the follow-up and remained non-compliant to the medications were excluded from the final data analysis as per standard protocols of the per-protocol analysis.  Results: A total of 252 patients were included. In Group A and Group B, 6/126 (4.76%) and 8/126 (6.35%) of the patients were lost to follow-up, respectively. The non-compliance rate in Group A was 5/126 (3.97%), compared to Group B with 3/126 (2.38%). Finally, the per-protocol analysis of the results included 115 patients in each group. Baseline characteristics, including demographics, lifestyle, and clinical factors, were comparable between groups with p-values of 0.138 for age, 0.356 for gender, 0.126 for BMI, 0.495 for residence, 0.500 for water source, 0.866 for meal habit, 0.863 for smoking, 0.188 for nonsteroidal anti-inflammatory drug (NSAID) use, 0.145 for proton pump inhibitor (PPI) use, 0.213 for antibiotics, and 0.456 for treatment history. Both treatments effectively eradicated H. pylori, as determined by a negative urea breath test at four weeks post-treatment, with Group B showing a higher eradication rate of 96.5% compared to 92.2% in Group A, although the difference was not statistically significant (p = 0.153). There was no difference in adverse effects in both treatment groups (p-value > 0.05).  Conclusion: The study found that while the vonoprazan-based regime exhibited a slightly higher eradication rate of H. pylori compared to lansoprazole, the difference was not statistically significant. It was concluded that both regimens demonstrated comparable efficacy and similar profiles of adverse effects in treating H. pylori infection.

Deciphering DNA repair gene mutational landscape in uterine corpus endometrial carcinoma patients using next generation sequencing.

Uterine Corpus Endometrial Carcinoma (UCEC) is a significant health concern with a complex genetic landscape impacting disease susceptibility and progression. This study aimed to unravel the spectrum of DNA repair gene mutations in Pakistani UCEC patients through Next Generation Sequencing (NGS) and explore their potential functional consequences via downstream analyses. NGS analysis of genomic DNA from 30 UCEC patients was conducted to identify clinically significant pathogenic mutations in DNA repair genes. This analysis revealed mutations in 4 key DNA repair genes: BRCA1, BRCA2, APC, and CDH1. Kaplan-Meier (KM) analysis was employed to assess the prognostic value of these mutations on patient overall survival (OS) in UCEC. To delve into the functional impact of these mutations, we performed RT-qPCR, immunohistochemistry (IHC), and western blot analyses on the mutated UCEC samples compared to their non-mutated counterparts. These results unveiled the up-regulation in the expression of the mutated genes, suggesting a potential association between the identified mutations and enhanced gene activity. Additionally, targeted bisulfite sequencing analysis was utilized to evaluate DNA methylation patterns in the promoters of the mutated genes. Strikingly, hypomethylation in the promoters of BRCA1, BRCA2, APC, and CDH1 was observed in the mutated UCEC samples relative to the non-mutated, indicating the involvement of epigenetic mechanisms in the altered gene expression. In conclusion, this study offers insights into the genetic landscape of DNA repair gene mutations in Pakistani UCEC patients. The presence of pathogenic mutations in BRCA1, BRCA2, APC, and CDH1, coupled with their down-regulation and hypermethylation, suggests a convergence of genetic and epigenetic factors contributing to genomic instability in UCEC cells. These findings enhance our understanding of UCEC susceptibility and provide potential avenues for targeted therapeutic interventions in Pakistani UCEC patients.

Immune modulation and prognostic significance of MCM10 in pan-cancer: a comprehensive analysis.

BACKGROUND: Oncogenic processes in cancer are often characterized by dysregulation of critical genes. Our study focused on the minichromosome maintenance 10 replication initiation factor (MCM10) gene's expression and its potential diagnostic and prognostic implications in pan-cancer. METHOD: Leveraging large-scale genomic datasets, and experimental validation we embarked on a comprehensive analysis to shed light on the diagnostic and prognostic role of MCM10. RESULTS: Our findings underscore the wide-ranging up-regulation of MCM10 across 24 major cancer types, positioning it as a ubiquitous player in tumorigenesis. Significantly, MCM10 up-regulation was strongly associated with poorer overall survival in Kidney Renal Papillary Cell Carcinoma (KIRP), Liver Hepatocellular Carcinoma (LIHC), and Lung Adenocarcinoma (LUAD), emphasizing its potential as a valuable prognostic marker in these cancers. While genetic mutations often drive oncogenic processes, our mutational analysis revealed the relative stability of MCM10 in KIRP, LIHC, and LUAD. This suggests that epigenetic (hypomethylation) and non-mutational regulatory mechanisms predominantly govern MCM10 expression in these cancer types. Further analyses demonstrated positive correlations between MCM10 expression and immune cell infiltration, particularly CD8+ T cells and CD4+ T cells, offering insights into the gene's influence on the tumor immune microenvironment. Additionally, pathway enrichment analysis highlighted MCM10-associated genes' involvement in crucial signaling pathways, such as the cell cycle, DNA replication, and repair. Exploring the therapeutic potential, we examined important drugs capable of regulating MCM10 expression, opening doors to personalized treatment strategies. CONCLUSION: Our study elucidates the multifaceted roles of MCM10 in KIRP, LIHC, and LUAD. Its pervasive up-regulation, prognostic significance, epigenetic regulation, and influence on the immune microenvironment provide valuable insights into these cancers. This research contributes to the growing body of evidence surrounding MCM10 and invites further investigation, validation, and potential translational efforts to harness its clinical relevance.

Elucidating cuproptosis-related gene SLC31A1 diagnostic and prognostic values in cancer.

OBJECTIVES: Cancer remains a global health challenge, necessitating the identification of novel biomarkers and therapeutic targets. Cuproptosis, a recently recognized form of cell death linked to copper metabolism, presents a promising avenue for anticancer strategies. We investigated the clinical significance of SLC31A1, a key regulator of cuproptosis, in multiple cancer types, aiming to elucidate its potential as a diagnostic biomarker, prognostic, indicator and therapeutic target. METHODS: We conducted a pan-cancer analysis through TIMER2.0, evaluating SLC31A1 expression across multiple cancer types. Survival analysis was performed using KM plotter. Expression validation was carried out using UALCAN and Human Protein Atlas (HPA) databases. Methylation analysis was conducted with the help of ULACAN and OncoDB. Mutational analysis was performed using cBioPortal database. Immune infiltration analysis via the TIMER2.0 and gene enrichment analysis via the Metascape were performed to gain insights into the potential mechanisms underlying SLC31A1's role in cancer. Finally, Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to confirm SLC31A1 expression in clinical samples. RESULTS: Out of analyzed cancer, SLC31A1 exhibited significant up-regulation and correlation with worse overall survival (OS) across Breast Cancer (BRCA), Cervical Squamous Cell Carcinoma (CESC), Head and Neck Squamous Cell Carcinoma (HNSC), and Esophageal Carcinoma (ESCA). Mutational and promoter methylation analyses further revealed that hypomethylation is the major cause of SLC31A1 overexpression among BRCA, CESC, HNSC, and ESCA. Immune infiltration analysis showed significant associations between SLC31A1 expression and the presence of CD8+ T cells, CD4+ T cells, and macrophages in the tumor microenvironment. Gene enrichment analysis provided valuable insights into potential molecular pathways in context to BRCA, CESC, HNSC, and ESCA. Furthermore, when SLC31A1 was analyzed using clinical samples through RT-qPCR, this gene showed promising diagnostic potential, reflected by high Area Under the Curve (AUC) values. CONCLUSION: Our pan-cancer study highlights the up-regulation of SLC31A1 and its correlation with worse OS in BRCA, CESC, HNSC, and ESCA. In sum, outcomes of this study showed that SLC31A1 could be a potential biomarker and novel therapeutic target of BRCA, CESC, HNSC, and ESCA.

Comprehensive multi-level expression profiling of key biomarkers in breast cancer patients.

OBJECTIVES: In this comprehensive breast cancer (BC) study, we aimed to identify, validate, and characterize key biomarkers with significant implications in BC diagnosis, prognosis, and as therapeutic targets. METHODS: Our research strategy involved a multi-level methodology, combining bioinformatic analysis with experimental validation. RESULTS: Initially, we conducted an extensive literature search to identify BC biomarkers, selecting those with reported accuracies exceeding 20% in specificity and sensitivity. This yielded nine candidate biomarkers, which we subsequently analyzed using Cytoscape to identify a few key biomarkers. Based on the degree method, we denoted four key biomarkers, including progesterone receptor (PGR), epidermal growth factor receptor (EGFR), estrogen receptor 1 (ESR1), and Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2). Expression analysis using The Cancer Genome Atlas (TCGA) dataset revealed that PGR and EGFR exhibited significant (p-value < 0.05) down-regulation in BC samples when compared to controls, while ESR1 and ERBB2 showed up-regulation. To strengthen our findings, we collected clinical BC tissue samples from Pakistani patients and performed expression verification using real-time quantitative polymerase chain reaction (RT-qPCR). The results aligned with our initial TCGA dataset analysis, further validating the differential expression of these key biomarkers in BC. Furthermore, we utilized receiver operating characteristic (ROC) curves to demonstrate the diagnostic use of these biomarkers. Our analysis underscored their accuracy and sensitivity as diagnostic markers for BC. Survival analysis using the Kaplan-Meier Plotter tool revealed a prognostic significance of PGR, ESR1, EGFR, and ERBB2. Their expression levels were associated with poor overall survival (OS) of BC patients, shedding light on their roles as prognostic indicators in BC. Lastly, we explored DrugBank to identify drugs that may reverse the expression patterns , and estradiol, decitabine, and carbamazepine were singled out. CONCLUSION: Our study gives valuable insight into BC biomarkers, for diagnosis and prognosis. These findings have implications for BC management using personalized and targeted therapeutic approaches for BC patients.