Exploring the Concordance Between High-Risk Human Papillomavirus Infections in Cervical and Oral Sites Among Females: A Cross-Sectional Study in Punjab, Pakistan.

PURPOSE: Human papillomavirus (HPV) is widely recognized as a key contributing factor in cervical and oropharyngeal cancers. However, there has been limited research on the prevalence of concurrent HPV infections in various anatomic regions. This study aimed to investigate the prevalence and specific types of high-risk HPV (HR-HPV) infections in the cervical and oral regions of females in Punjab, Pakistan. METHODS: We conducted a cross-sectional study involving women seeking care for general gynecologic issues at the gynecologic Outpatient Department of Lady Wallington Hospital in Lahore. After interviews and clinical examinations, we collected whole-saliva samples and high vaginal swabs from each participant. HR-HPV detection and genotyping were performed using real-time polymerase chain reaction at both the anatomic sites. RESULTS: In this study, 170 females, averaging 35.36 ± 8.305 years, participated. HR-HPV infection was more prevalent in the cervix (83/170 [48.8%]) than in the oral cavity (19/170 [11.2%]). Concordant HPV infections occurred in 10/170 participants (5.9%). HPV 16 was the most common genotype in cervical and oral locations, at rates of 21.8% and 5.3%, respectively, among concordant HR-HPV types. Socioeconomic status (P = .013), age at first sexual intercourse (P = .015), and history of oral sex (P = .01) were significantly associated with concurrent HR-HPV infection in both regions. CONCLUSION: This study suggests that HR-HPV cervical infections may increase the risk of oral transmission, especially during orogenital sexual practices. Thus, it is important to recognize that HPV infections may be linked in both areas. We emphasize the importance of comprehensive cervical and oral examinations and HPV vaccination in young women irrespective of their sexual practices.

Comprehensive Analysis of Oral Squamous Cell Carcinomas: Clinical, Epidemiological, and Histopathological Insights With a Focus on Prognostic Factors and Survival Time.

BACKGROUND AND OBJECTIVES: Oral squamous cell carcinoma (OSCC) is one of the most common malignancies in the head and neck region. Particularly, high incidence rates are observed in South and Southeast Asia, attributed to the widespread use of the carcinogenic areca nut. This study aimed to investigate the clinical, epidemiological, and histopathological features of OSCC, identify prognostic factors impacting disease-free survival, and determine a post-diagnosis disease-free survival time of OSCC patients. METHODOLOGY: Employing a descriptive cross-sectional design, the study conducted a thorough examination of the clinical, epidemiological, and histopathological aspects of OSCC among patients seeking care at a tertiary healthcare facility. Participants were personally interviewed if available, while information for unreachable or deceased individuals was extracted from archival patient records in the Oral and Maxillofacial Surgery Department, Bakhtawar Amin Medical and Dental College, Multan, Pakistan. Data analysis was performed with a significance level set at p ≤ 0.05. RESULTS: The mean age of the patients was 54.16 ± 11.1, with a notable concentration in the 41 years and above age group, indicating a significant prevalence of OSCC in this population. The data revealed a gender bias toward males, and a substantial proportion of patients, particularly those aged 41 years and above, had unfortunately passed away. Statistical analysis using the Fisher exact test showed a significant association between age groups and patients' current living status (p-value < 0.05). CONCLUSION: Histopathologically, moderately differentiated OSCC was the most frequently encountered grade, and surgery emerged as the predominant treatment modality. The majority of patients studied had a survival period of three years or less, emphasizing the need for further exploration of factors influencing prognosis and treatment outcomes in OSCC.

Concomitant transthyretin cardiac amyloidosis in patients undergoing TAVR for aortic stenosis: A systemic review and meta-analysis.

OBJECTIVE: Transcatheter aortic valve replacement (TAVR) is a successful treatment for aortic stenosis (AS) patients, and previous studies indicate favorable outcomes for those with concomitant aortic stenosis and transthyretin-associated cardiac amyloidosis (TTRCA-AS). However, the impact of TAVR on more adverse outcomes in TTRCA-AS patients compared to those with AS alone is still uncertain, with conflicting findings reported in the literature. METHODS: PubMed and Scopus were extensively searched from inception till August 2021. Studies were included if they reported data for prevalence and outcomes including mortality and cardiovascular-related hospitalization events in TTRCA-AS patients referred for TAVR. The data for these outcomes were pooled using a random effects model and forest plots were created. RESULTS: After initially screening 146 articles, 6 were shortlisted for inclusion in our analysis. Pooled analysis demonstrated a 13.3% [95% CI: 10.9-16.5; p = 0.307] prevalence of TTRCA in patients with AS undergoing TAVR. The incidence of mortality and cardiovascular (CV) hospitalization in patients with TTRCA-AS undergoing TAVR were 28.3% [95% CI: 18.7-39.0, p = 0.478] and 21.1% [95% CI: 10.2-34.5, p = 0.211], respectively. CONCLUSION: The overall pooled TTRCA-AS prevalence was reported to be 13.3% in AS patients who underwent TAVR. Furthermore, transthyretin-associated CA was found to be associated with an increased risk of mortality and hospitalization. Large patient population studies are required to assess the safety and efficacy of TAVR in TTRCA-AS patients, as current research report data from small patient cohorts.

Shake It Up Baby Now: The Changing Focus on TWIST1 and Epithelial to Mesenchymal Transition in Cancer and Other Diseases.

TWIST1 is a transcription factor that is necessary for healthy neural crest migration, mesoderm development, and gastrulation. It functions as a key regulator of epithelial-to-mesenchymal transition (EMT), a process by which cells lose their polarity and gain the ability to migrate. EMT is often reactivated in cancers, where it is strongly associated with tumor cell invasion and metastasis. Early work on TWIST1 in adult tissues focused on its transcriptional targets and how EMT gave rise to metastatic cells. In recent years, the roles of TWIST1 and other EMT factors in cancer have expanded greatly as our understanding of tumor progression has advanced. TWIST1 and related factors are frequently tied to cancer cell stemness and changes in therapeutic responses and thus are now being viewed as attractive therapeutic targets. In this review, we highlight non-metastatic roles for TWIST1 and related EMT factors in cancer and other disorders, discuss recent findings in the areas of therapeutic resistance and stemness in cancer, and comment on the potential to target EMT for therapy. Further research into EMT will inform novel treatment combinations and strategies for advanced cancers and other diseases.

Seroprevalence and haemato-biochemical effects of bovine leucosis in buffalo, Punjab, Pakistan.

Enzootic bovine leucosis is caused by bovine leukaemia virus (BLV), a Deltaretrovirus belonging to the family Retroviridae. BLV causes huge economic losses to the dairy industry in the form of decreased milk production, premature culling, and poor reproductive performance of the animals. The aim of the present study was to determine the seroprevalence of BLV infection in buffalo in two districts of Punjab, Pakistan. A total of 384 samples were collected and analysed using a commercial indirect enzyme-linked immunosorbent assay (ELISA) to investigate the seroprevalence of BLV through the detection of the anti-BLV gp51 antibody. A predesigned data questionnaire proforma was employed to find out the association of risk factors with disease. Overall, 18.2% of buffaloes were seropositive for BLV in the study population. The results revealed a significant association (P < 0.05) of age with BLV infection. Furthermore, milk yield and pregnancy had a significant association with the seroprevalence of BLV infection in buffalo whereas no significant association was found with sex, breeding, and health status. Biochemical and oxidative stress markers revealed a significant decrease in liver enzymes alanine transaminase (ALT) and aspartate transaminase (AST), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in seropositive animals as compared to healthy animals. It is concluded that BLV has a considerable prevalence in buffalo in Punjab, Pakistan and there is a dire need to investigate the disease epidemiology at both national and international levels and strategies should be developed to implement an effective control program.

Association between e-cigarette use and myocardial infarction: a systematic review and meta-analysis.

BACKGROUND: The popularity of e-cigarettes has risen dramatically over the last few years, particularly among the younger population. Although the use of combustible cigarettes has established evidence to be associated with the development of several adverse cardiopulmonary diseases, the investigations regarding the prospective long-term effects of e-cigarette use on the cardiovascular system have just begun. We set to investigate if there is an association between the history of MI and e-cigarette use among smokers and non-smokers? METHODS: The current review aims to assess the association of myocardial infarction with e-cigarette consumption. PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials (CENTRAL) were queried up to October 2022 to identify articles assessing the incidence of myocardial infarction among e-cigarette users. Data were meta-analyzed using a random-effects model to derive odds ratios (OR) and 95% confidence intervals. RESULTS: Nine studies involving 984,764 patients were included. The mean age of e-cigarette smokers was less than the controls, and female participants dominated the sample size. E-cigarette users were associated with increased odds of MI than non-users [OR = 1.44; 95% CI (1.22, 1.74); P < 0.0001]. Dual users were also associated with increased odds of MI with large effect when compared to non-users [OR = 4.04; 95% CI (3.40, 4.81); P < 0.00001]. CONCLUSIONS: Dual use is associated with an increased risk of MI than e-cigarette use only. Similarly, dual and solely e-cigarette consumption patterns of nicotine delivery are at a higher risk of MI than non-smokers.

Minimal residual disease status is the prognostic determinant following high-dose treatment for patients with multiple myeloma.

BACKGROUND: The presence of minimal residual disease (MRD+) following autologous stem cell transplantation (ASCT) in multiple myeloma represents a poor prognostic factor for progression-free survival (PFS) and overall survival (OS). METHODS: At our department, we recommend lenalidomide maintenance for patients who are MRD+ after ASCT, while MRD-negative (MRD-) patients, after information about the national guidelines, were not advised to follow this regimen. RESULTS: Out of the total 228 patients, 175 received ASCT following first-line induction (MRD- 92 (53%), MRD+ 83 (47%), at 2 months post-ASCT), while 53 underwent ASCT after second-line treatment (MRD- 27 (51%), MRD+ 26 (49%), at the same time point). Comparatively, MRD- patients who did not receive maintenance demonstrated better OS than MRD+ patients who received upfront ASCT and maintenance treatment (96% vs. 86%, p = 0.030, at 3 years). However, nonsignificant difference was found in PFS (76% vs. 62%, at 3 years). Furthermore, second-line ASCT, MRD- non-maintained patients exhibited significantly better PFS than MRD+ (71% vs. 27%, p > 0.001, at 3 years). However, OS was better but nonsignificant (96% vs. 76%, at 3 years). Fluorescence in situ hybridization (FISH) analysis was performed on 141 out of the 228 patients. Of these, 85 (60%) patients were deemed standard risk (SR), and 56 (40%) were classified as high risk (HR). In the SR cohort, MRD- patients exhibited better PFS and OS than MRD+ patients (71% vs. 59% and 100% vs. 85%, respectively). In the HR cohort, the MRD- patients showed superior PFS but similar OS compared to MRD+ patients (66% vs. 42% and 81% vs. 80%, respectively). CONCLUSIONS: Our results indicate that being MRD- is a more crucial prognostic factor for the 3-year PFS and OS than the presence of high-risk cytogenetic markers or undergoing maintenance treatment. The latter appears insufficient, particularly for MRD+ patients following ASCT in the second-line setting, suggesting that these patients may require a more intensive treatment approach.

Molecular identification and infection pathology of Mycobacterium spp. in captive wild animals in Pakistan.

INTRODUCTION: Animal tuberculosis is an infectious, chronic, granulomatous, and debilitating disease affecting animals as well as humans. However, in recent decades, there have been many endemic geographic localities where animal tuberculosis has been identified in wildlife reservoirs, limiting the eradication program in cattle. This study aimed to identify animal tuberculosis in captive zoo animals in Pakistan. METHODOLOGY: In total, 185 morbid zoo animals were brought for postmortem examination at a veterinary postmortem facility. During the macroscopic examination, these animals were thoroughly examined for the presence of suggestive gross lesions of animal tuberculosis (granulomas/tubercles), and the pattern and distribution of these lesions in different organs. The Ziehl-Neelsen (ZN) staining was performed on smears prepared from granulomatous lesions of lung tissue followed by molecular identification of M. bovis and M. tuberculosis DNA using polymerase chain reaction (PCR). RESULTS: The postmortem examination revealed that 8.1% (15/185) of animals had gross tuberculosis lesions on the lungs and lymph nodes. The ZN staining of tissue smears showed 5.40% positivity while M. bovis and M. tuberculosis DNA was identified in 3.78 % and 1.1% of investigated animals, respectively. CONCLUSIONS: The study showed that animal tuberculosis is prevalent among wildlife in Pakistan and it may pose serious public health concerns to the people visiting these zoos and wildlife parks.

A MYC-controlled redox switch protects B lymphoma cells from EGR1-dependent apoptosis.

Refractory and relapsed B cell lymphomas are often driven by the difficult-to-target oncogene MYC. Here, we report that high MYC expression stimulates proliferation and protects B lymphoma cells from apoptosis under normal oxidative stress levels and that compounds including N-acetylcysteine (NAC) and vitamin C (VitC) induce apoptosis by reducing oxidative stress. NAC and VitC injections effectively reduce tumor growth in lymphoma cells with high MYC expression but not in those with low MYC expression. MYC knockdown confers tumor resistance to NAC and VitC, while MYC activation renders B cells sensitive to these compounds. Mechanistically, NAC and VitC stimulate MYC binding to EGR1 through Cys117 of MYC, shifting its transcriptional output from cell cycle to apoptosis gene expression. These results identify a redox-controlled mechanism for MYC's role in maintaining proliferation and preventing apoptosis, offering a potential therapeutic rationale for evaluating NAC or VitC in patients with MYC-driven B cell lymphoma.

Frequency and Types of Periapical Radiographic Lesions Associated With Pulpitis in a Tertiary Care Hospital.

Objective This cross-sectional study aimed to determine the frequency and types of periapical radiographic lesions (PARLs) associated with pulpitis in patients visiting a tertiary care hospital. Methodology A sample of patients diagnosed with pulpitis, aged 18 years or older, was recruited following a convenient sampling technique. Clinical examinations were conducted to confirm the diagnosis, and radiographic evaluations, including periapical (PA), occlusal, orthopantomogram (OPG), and cone beam computed tomography (CBCT) radiographs were obtained. The radiographs were evaluated for the presence of PA lesions, and the type, size, and location of the lesions were documented. Data were analyzed using IBM SPSS Statistics for Windows, Version 25.0 (IBM Corp., Armonk, NY, USA). Results A total of 120 patients (equal gender ratio) with a mean age of 32.6 ± 6.39 years participated in the study. PA views were the most frequently performed radiographic view (86.7%), followed by occlusal views (8.3%). The most prevalent radiographic lesion was the widening of the periodontal ligament (PDL) space (34.2%), followed by PA granuloma (17.5%) and PA cyst (10.8%). The most frequently encountered diagnosis was pulpitis (51.7%), followed by irreversible pulpitis with apical periodontitis (25.8%). Education level, swelling, pus discharge, medicine history, and tooth wear showed statistically significant associations (P ≤ 0.05) with the variables under investigation. Conclusions The most common lesions observed were widening of the PDL space, PA granuloma, and PA cyst. The findings contribute to the local epidemiological and clinical data, enriching the existing database. Understanding the prevalence and characteristics of PA lesions associated with pulpitis can aid in accurate diagnosis and treatment planning for patients with pulpal pathologies.

Screening of four signature genes for clinical testing through bioinformatics and in vitro methods in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSC) is the 6th most common cancer around the globe; its underlying molecular mechanisms and accurate molecular markers are still lacking. In this study, we explored hub genes and their potential signaling pathways through which these genes participate in the development of HNSC. The GSE23036 gene microarray dataset was attained from the GEO (Gene Expression Omnibus) database. Hub genes were identified via the Cytohubba plug-in application of the Cytoscape. The Cancer Genome Atlas (TCGA) datasets and cell lines (HOK and FuDu) were used to evaluate expression variations in the hub genes. Moreover, promoter methylation, genetic alteration, gene enrichment, miRNA network, and immunocyte infiltration analysis were also performed to confirm the oncogenic role and biomarker potential of the hub genes in HNSC patients. Based on the hub gene analysis results, four hub genes, including KNTC1 (Kinetochore Associated 1), CEP55 (Centrosomal protein of 55 kDa), AURKA (Aurora A Kinase), and ECT2 (Epithelial Cell Transforming 2), with the highest degree scores were denoted as hub genes. All these four genes were significantly up-regulated in HNSC clinical samples and cell lines relative to their counterparts. Overexpression of KNTC1, CEP55, AURKA, and ECT2 was also associated with poor survival and various clinical parameters of the HNSC patients. Methylation analysis through targeted bisulfite sequencing of HOK and FuDu cell lines revealed that the overexpression of KNTC1, CEP55, AURKA, and ECT2 hub genes was due to their promoter hypomethylation. Moreover, higher expressions of KNTC1, CEP55, AURKA, and ECT2 were positively correlated with the abundance of the CD4+ T cells and macrophage while with the reduction of CD8+ T cells in HNSC samples. Finally, gene enrichment analysis showed that all hub genes are involved in "nucleoplasm, centrosome, mitotic spindle, and cytosol" pathways. In conclusion, the KNTC1, CEP55, AURKA, and ECT2 genes could be potential biomarkers for HNSC patients and provide a novel insight into the diagnosis and treatment of the disease.

Deciphering the biodesulfurization pathway employing marine mangrove Bacillus aryabhattai strain NM1-A2 according to whole genome sequencing and transcriptome analyses.

In the biogeochemical cycle, sulfur oxidation plays a vital role and is typically referred to as the elemental sulfur or reductive sulfide oxidation process. This study aimed to characterize a subtropical mangrove-isolated bacterial strain using biochemical, whole-genome, and transcriptome sequencing analyses to enhance our understanding of sulfur metabolism and biodegradation from a molecular genetic perspective. Strain NM1-A2 was characterized as Gram-positive and found to have a close molecular phylogenetic relationship with Bacillus aryabhattai. NM1-A2 efficiently converted dibenzothiophene (DBT) into 2-hydroxybiphenyl (2-HBP) via a 4S pathway with 95% efficiency, using enzymes encoded by the dsz operon (dszA, dszB, and dszC), which determine monooxygenases (DszA & DszC) and desulfinase (DszB). The whole-genome sequence of NM1-A2 had a length of approximately 5,257,678 bp and included 16 sulfur metabolism-related genes, featuring the ABC transport system, small subunit (ssu) and cysteine (cys) gene families, and adenosine 5'-phosphosulfate (APS) and 3'-phosphoadenosine-5'-phosphosulfate (PAPS) biosynthesis-related genes. Transcriptomic analysis of NM1-A2 using three sulfur groups-magnesium sulfate (MS), sulfur powder (SP), and sodium thiosulfate (ST) resulted in a significant number of differentially expressed genes (1200, 2304, and 2001, respectively). This analysis revealed that intracellular cysteine concentration directly regulated the expression of cys and ssu genes. Sulfate did not directly affect cys gene expression but repressed ssu gene expression. The cys gene expression levels decreased during the conversion of sulfate to sulfide and cysteine. The transcriptomic data was validated by analyzing the expression patterns of NM1-A2 using real-time quantitative PCR validation analysis. The expression levels of cysl, mccB, and nrnA were significantly upregulated, while cysH, metB, and sat were downregulated in the SP, ST, and MS groups, respectively. This research contributes to our understanding of marine mangrove microorganisms' bacterial efficiency through characterization, whole-genome, and transcriptome sequencing-based molecular degradation of organic compounds in the mangrove ecosystem, which may enhance nutrient availability.

ROS-lowering doses of vitamins C and A accelerate malignant melanoma metastasis.

Oxidative stress is a barrier of migration and metastasis for malignant melanoma cells. Consequently, reducing oxidative stress with the antioxidant N-acetylcysteine (NAC) stimulates melanoma cell migration in vitro and metastasis in vivo. However, it is not yet known whether the NAC effect is shared with other antioxidants. Here, we screened 104 redox-active compounds and identify 27 that increase migration of human malignant melanoma cells in two doses. Validation experiments in four cell lines and four drug doses resulted in a list of 18 compounds which were ranked based on their ability to increase migration and reduce ROS levels; vitamin C (VitC) ranked as number one, followed by the vitamin E analogue Trolox and several carotenoids and Vitamin A-related compounds. Four diet-relevant compounds from this list-VitC, ß-carotene, retinyl palmitate, and canthaxanthin-were selected and found to accelerate metastasis in mice with BRAFV600E-driven malignant melanoma. Genomics analyses revealed that the transcription factor BACH1 is activated following antioxidant administration and knockout of Bach1 in mouse melanoma cells reduced lymph node and liver metastasis in xenograft mouse models. We conclude that a broad range of antioxidants accelerate melanoma migration and metastasis and that BACH1 is functionally linked to melanoma metastasis in vivo.

Synthesis of nickel nanowires (Ni-NWs) as high ferromagnetic material by electrodeposition technique.

Metallic nanowires (NWs) and their different compounds display incredible prospects for their use in various applications including media storage, sensor and solar cell devices along with the biological drug delivery systems. In this research work, the metallic NWs like nickel nanowires (Ni-NWs) are synthesized successfully by employing electrodeposition process. Anodic aluminum oxide (AAO) templates are employed as a platform with copper metal coating which acts as an active cathode. The synthesized Ni-NWs are examined through various characterization techniques including X-ray diffraction (XRD), scanning electron microscope (SEM) and vibrating sample magnetometer (VSM) to study the crystal structure, surface morphology and magnetic properties, respectively. The XRD analysis shows the development of various diffraction planes like Ni (111), Ni (200), Ni (220) which confirms the formation of polycrystalline nickel NWs. The SEM analysis reveals that the range of diameter and length of nickel NWs are found to be ∼160 to 200 and ∼4 to 11 micron respectively showing high aspect ratio (ranged from ∼200 to 300). The ferromagnetic behavior of Ni-NWs is confirmed by the hysteresis loop carried out for parallel and perpendicular configurations having Hc = 100 and 206 Oe, respectively. The obtained results suggest that the synthesized Ni- NWs may be used for high-density media storage devices.

Generation of NK cells with chimeric-switch receptors to overcome PD1-mediated inhibition in cancer immunotherapy.

Multiple myeloma (MM) is an incurable hematological cancer, in which immune checkpoint inhibition (ICI) with monoclonal antibodies (mAbs) has failed due to uncontrollable immune responses in combination therapies and lack of efficacy in monotherapies. Although NK cell-specific checkpoint targets such as NKG2A and KIRs are currently being evaluated in clinical trials, the clinical impact of NK cells on the PD1 cascade is less well understood compared to T cells. Furthermore, while NK cells have effector activity within the TME, under continuous ligand exposure, NK cell dysfunctionality may occur due to interaction of PD1 and its ligand PD-L1. Due to above-mentioned factors, we designed novel NK cell specific PD1-based chimeric switch receptors (PD1-CSR) by employing signaling domains of DAP10, DAP12 and CD3ζ to revert NK cell inhibition and retarget ICI. PD1-CSR modified NK cells showed increased degranulation, cytokine secretion and cytotoxicity upon recognition of PD-L1+ target cells. Additionally, PD1-CSR+ NK cells infiltrated and killed tumor spheroids. While primary NK cells (pNK), expressing native PD1, showed decreased degranulation and cytokine production against PD-L1+ target cells by twofold, PD1-CSR+ pNK cells demonstrated increased activity upon PD-L1+ target cell recognition and enhanced antibody-dependent cellular cytotoxicity. PD1-CSR+ pNK cells from patients with MM increased degranulation and cytokine expression against autologous CD138+PD-L1+ malignant plasma cells. Taken together, the present results demonstrate that PD1-CSR+ NK cells enhance and sustain potent anti-tumor activity in a PD-L1+ microenvironment and thus represent a promising strategy to advance adoptive NK cell-based immunotherapies toward PD-L1+ cancers.

Integration of Microbial Transformation Mechanism of Polyphosphate Accumulation and Sulfur Cycle in Subtropical Marine Mangrove Ecosystems with Spartina alterniflora Invasion.

Excessive phosphorus can lead to eutrophication in marine and coastal ecosystems. Sulfur metabolism-associated microorganisms stimulate biological phosphorous removal. However, the integrating co-biotransformation mechanism of phosphorus and sulfur in subtropical marine mangrove ecosystems with Spartina alterniflora invasion is poorly understood. In this study, an ecological model of the coupling biotransformation of sulfur and phosphorus is constructed using metagenomic analysis and quantitative polymerase chain reaction strategies. Phylogenetic analysis profiling, a distinctive microbiome with high frequencies of Gammaproteobacteria and Deltaproteobacteria, appears to be an adaptive characteristic of microbial structures in subtropical mangrove ecosystems. Functional analysis reveals that the levels of sulfate reduction, sulfur oxidation, and poly-phosphate (Poly-P) aggregation decrease with increasing depth. However, at depths of 25-50 cm in the mangrove ecosystems with S. alterniflora invasion, the abundance of sulfate reduction genes, sulfur oxidation genes, and polyphosphate kinase (ppk) significantly increased. A strong positive correlation was found among ppk, sulfate reduction, sulfur oxidation, and sulfur metabolizing microorganisms, and the content of sulfide was significantly and positively correlated with the abundance of ppk. Further microbial identification suggested that Desulfobacterales, Anaerolineales, and Chromatiales potentially drove the coupling biotransformation of phosphorus and sulfur cycling. In particular, Desulfobacterales exhibited dominance in the microbial community structure. Our findings provided insights into the simultaneous co-biotransformation of phosphorus and sulfur bioconversions in subtropical marine mangrove ecosystems with S. alterniflora invasion.

Molecular characterization and risk factors of oral high-risk human papillomavirus among females in Punjab, Pakistan.

BACKGROUND: The development of oral and oropharyngeal cancers is associated with human papillomavirus (HPV) infection. However, debate exists about the prevalence of high-risk oral HPV (HR-HPV) and its associated risk factors. This study evaluated the distribution of genotypes and associated risk factors of oral HR-HPV infection in the normal oral mucosa of the Pakistani female population with general gynecological problems. METHODS: A total of 200 females from a regional gynecological hospital in Pakistan were included in this cross-sectional study. A self-administered questionnaire was carried out, followed by the study participants' oral and dental examinations. Whole saliva was collected by a drooling method. The viral DNA extraction and oral HR-HPV genotyping were detected via real-time polymerase chain reaction. RESULTS: Among the 200 females (mean age, 37.76 years), 22 females (11%) were positive for oral HR-HPV DNA. Single oral HR-HPV infection was seen in 8%, whereas co-infection was observed in 3% with HPV16 and HPV18 most common genotypes. Comparison of the risk factors like oral sex history odds ratio (OR 8.21, 95% confidence interval [CI] 1.85-28.16; p < 0.005), and open-mouth kissing (OR, 5.17; 95% CI 1.48-27.41; p = 0.005) with oral HR-HPV infection was found to be significantly associated. CONCLUSION: In Pakistan, oral HR-HPV-positive infection is not uncommon; HPV16 and HPV18 are the most frequent genotypes. Furthermore, this study also provides data that oral HR-HPV positive infection was significantly associated with sexual behaviors. Therefore, preventive health efforts, like health education and vaccination, should be practiced.

Whole-genome analysis and evolutionary characterization of cervical and oral human papillomavirus 16.

High-throughput genome-wide sequencing has revealed high genomic variability of HPV16 in different geographic regions which is the most predominant genotype in human papillomavirus (HPV)-associated malignancies. Analysis of the HPV16 by whole-genome sequence (WGS) is an advanced method for the identification of mutations in the genome. There is limited information about HPV16 diversity in Pakistan, especially at the genomic level. Till now, WGS for HPV16 has not been previously reported in Pakistan. The current study has sequenced three HPV16 viral genomes, from two cervical and one oral cavity positive sample of women presented with general gynecological problems without any evidence of precancerous or cancerous lesions using an ion ampliseq customized panel. Sequencing analysis detected 38 variations, including single-nucleotide polymorphisms (SNPs) and two Indels, across three samples with the highest number of SNPs present in E1, E2, and L2, respectively. A total of 20 non-synonymous and 11 synonymous mutations with amino acid substitutions (T1421C, G1515A, T2223C, T1389C, G1483A, and T2191C) were identified. The phylogenetic analysis revealed the genomes of HPV16 are closely associated with those reported from Thailand and the United States. These are the first HPV16 WGS from Pakistan. However, more research is needed with a large sample size from diversified areas to assess the carcinogenic consequences and impact of HPV vaccinations.

Adult Para Testicular Spindle Cell Rhabdomyosarcoma: A Case Report From Pakistan.

Para testicular or intra-scrotal Rhabdomyosarcomas (RMS) are rare. The spindle cell variant of rhabdomyosarcoma is the least common variant among embryonal subtypes. They are mostly seen in childhood but rarely reported in adults. We present a case of a 56-year-old man who presented with a three-year history of painless left inguinoscrotal swelling, which he initially ignored and misinterpreted as an Inguinal hernia but later sought medical help upon a progressive increase in the size of the swelling. Clinically and radiologically, there was sparing of the left testis and spermatic cord with normal testicular tumor markers and no evidence of lymphadenopathy or metastasis. Surgical exploration was performed with complete excision of the mass, followed by histopathology and immunocytochemistry, confirming the diagnosis of spindle cell rhabdomyosarcoma. Prompt recognition, early diagnosis, and appropriate surgical treatment are the hallmarks of management. Regular and strict follow-up is needed due to the rarity of diagnosis.

Conditioning with melphalan 200 mg/m2 and subsequent ASCT improves progression-free and overall survival in elderly myeloma patients compared to standard of care.

OBJECTIVES: Despite the effectiveness of newer drugs for the treatment of multiple myeloma (MM), the outcomes are further improved by subsequent autologous stem cell transplantation (ASCT). Data on effectiveness in older patients are limited. We compared outcomes in patients aged 65-75 years depending on whether they were treated with ASCT or not and compared those to outcomes in patients <65 years. METHODS: This was a retrospective, single-center study. We compared progression-free survival (PFS) and overall survival (OS) for all MM patients below and above the age of 65 years treated ± ASCT at the Karolinska University Hospital between 2010 and 2020. PFS and OS were calculated by the Kaplan-Meier method. Variables affecting PFS and OS were evaluated using Cox regression model. RESULTS: Both PFS and OS were improved in the group 65-75 years treated +ASCT compared to those treated pharmacologically (p = 0.008 and p < 0.001, respectively). There were no significant differences between patients <65 years and those 65-75 years treated with ASCT. CONCLUSION: The findings indicate that even patients >65 years should be evaluated as candidates for ASCT. An individualized approach supported by a frailty/geriatric assessment score could assist clinicians to select the appropriate treatment for each patient.