Deepfake Detection: Leveraging the Power of 2D and 3D CNN Ensembles

In the dynamic realm of deepfake detection, this work presents an innovative approach to validate video content. The methodology blends advanced 2-dimensional and 3-dimensional Convolutional Neural Networks. The 3D model is uniquely tailored to capture spatiotemporal features via sliding filters, extending through both spatial and temporal dimensions. This configuration enables nuanced pattern recognition in pixel arrangement and temporal evolution across frames. Simultaneously, the 2D model leverages EfficientNet architecture, harnessing auto-scaling in Convolutional Neural Networks. Notably, this ensemble integrates Voting Ensembles and Adaptive Weighted Ensembling. Strategic prioritization of the 3-dimensional model's output capitalizes on its exceptional spatio-temporal feature extraction. Experimental validation underscores the effectiveness of this strategy, showcasing its potential in countering deepfake generation's deceptive practices.Comment: 6 pages, 2 figure

Hierarchical modeling of melanocortin 1 receptor variants with skin cancer risk

The human MC1R gene is highly polymorphic among lightly pigmented populations, and several variants in the MC1R gene have been associated with increased risk of both melanoma and nonmelanoma skin cancers. The functional consequences of MC1R gene variants have been studied in vitro and in vivo in postulated causal pathways, such as G-protein-coupled signaling transduction, pigmentation, immune response, inflammatory response, cell proliferation, and extracellular matrix adhesion. In a case-control study nested within the Nurses' Health Study, we utilized hierarchical modeling approaches, incorporating quantitative information from these functional studies, to examine the association between particular MC1R alleles and the risk of skin cancers. Different prior matrices were constructed according to the phenotypic associations in controls, cell surface expression, and enzymatic kinetics. Our results showed the parameter variance estimates of each single nucleotide polymorphism (SNP) were smaller when using a hierarchical modeling approach compared to standard multivariable regression. Estimates of second-level parameters gave information about the relative importance of MC1R effects on different pathways, and odds ratio estimates changed depending on prior models (e.g., the change ranged from -21% to 7% for melanoma risk assessment). In addition, the estimates of prior model hyperparameters in the hierarchical modeling approach allow us to determine the relevance of individual pathways on the risk of each of the skin cancer types. In conclusion, hierarchical modeling provides a useful analytic approach in addition to the widely used conventional models in genetic association studies that can incorporate measures of allelic function

Chicken pox infection in patients undergoing chemotherapy: A retrospective analysis from a tertiary care center in India

SummaryThere is paucity of data on the incidence, severity and management of chicken pox in patients receiving active chemotherapy for cancer.From October 2010 to October 2011, patients were included in this study if they developed a chicken pox infection during their chemotherapy. The details of patients’ cancer diagnosis and treatment along with clinical and epidemiological data of the chicken pox infections were assessed from a prospectively maintained database.Twenty-four patients had a chicken pox infection while receiving chemotherapy and/or radiotherapy. The median age of the patients was 21 years, and two-thirds of the patients had solid tumor malignancies.Overall, eight (33%) patients had complications, six (25%) patients had febrile neutropenia, four (17%) had diarrhea/mucositis, and four (17%) had pneumonia. The median time for recovery of the infection and complications in the patients was 9.5 days (5–29 days), whereas for neutropenic patients, it was 6.5 days (3–14 days). The median time for recovery from chicken pox infections in neutropenic patients was 10 days (5–21 days), compared with 8.5 days (0–29 days) in non-neutropenic patients (P=0.84). The median time for recovery from infections was 8.5 days in patients with comorbidities (N=4), which was the same for patients with no comorbidities.The clinical presentation and complication rates of chicken pox in cancer patients, who were on active chemotherapy, are similar to the normal population. The recovery from a varicella infection and complications may be delayed in patients with neutropenia. The varicella infection causes a therapy delay in 70% of patients. Aggressive antiviral therapy, supportive care and isolation of the index cases remain the backbone of treatment

Genetic Variation in the Base Excision Repair Pathway, Environmental Risk Factors, and Colorectal Adenoma Risk

Cigarette smoking, high alcohol intake, and low dietary folate levels are risk factors for colorectal adenomas. Oxidative damage caused by these three factors can be repaired through the base excision repair pathway (BER). We hypothesized that genetic variation in BER might modify colorectal adenoma risk. In a sigmoidoscopy-based study, we examined associations between 182 haplotype tagging SNPs in 14 BER genes, and colorectal adenoma risk, and examined their potential role as modifiers of the effect cigarette smoking, alcohol intake, and dietary folate levels. Among all individuals, no statistically significant associations between BER SNPs and adenoma risk persisted after correction for multiple comparisons. However, among Asian-Pacific Islanders we observed two SNPs in FEN1 and one in NTHL1, and among African-Americans one SNP in APEX1 that were associated with colorectal adenoma risk. Significant associations were also observed between SNPs in the NEIL2 gene and rectal adenoma risk. Three SNPS modified the effect of smoking (MUTYH interaction p = 0.002; OGG1 interaction p = 0.013); FEN1 interaction p = 0.013)), one SNP in LIG3 modified the effect of alcohol consumption (interaction p = 0.024) and two SNPs in LIG3 modified the effect of dietary folate (interaction p = 0.001 and p = 0.08) on colorectal adenoma risk. These findings support a role for genetic variants in the BER pathway as potential modifiers of colorectal adenoma risk. Our findings strengthen the role of oxidative damage induced by key lifestyle and dietary risk factors in colorectal adenoma formation

Tobacco smoking, polymorphisms in carcinogen metabolism enzyme genes, and risk of localized and advanced prostate cancer: results from the California Collaborative Prostate Cancer Study

The relationship between tobacco smoking and prostate cancer (PCa) remains inconclusive. This study examined the association between tobacco smoking and PCa risk taking into account polymorphisms in carcinogen metabolism enzyme genes as possible effect modifiers (9 polymorphisms and 1 predicted phenotype from metabolism enzyme genes). The study included cases (n = 761 localized; n = 1199 advanced) and controls (n = 1139) from the multiethnic California Collaborative Case–Control Study of Prostate Cancer. Multivariable conditional logistic regression was performed to evaluate the association between tobacco smoking variables and risk of localized and advanced PCa risk. Being a former smoker, regardless of time of quit smoking, was associated with an increased risk of localized PCa (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0–1.6). Among non-Hispanic Whites, ever smoking was associated with an increased risk of localized PCa (OR = 1.5; 95% CI = 1.1–2.1), whereas current smoking was associated with risk of advanced PCa (OR = 1.4; 95% CI = 1.0–1.9). However, no associations were observed between smoking intensity, duration or pack-year variables, and advanced PCa. No statistically significant trends were seen among Hispanics or African-Americans. The relationship between smoking status and PCa risk was modified by the CYP1A2 rs7662551 polymorphism (P-interaction = 0.008). In conclusion, tobacco smoking was associated with risk of PCa, primarily localized disease among non-Hispanic Whites. This association was modified by a genetic variant in CYP1A2, thus supporting a role for tobacco carcinogens in PCa risk

Stability of the human faecal microbiome in a cohort of adult men

Characterizing the stability of the gut microbiome is important to exploit it as a therapeutic target and diagnostic biomarker. We metagenomically and metatranscriptomically sequenced the faecal microbiomes of 308 participants in the Health Professionals Follow-Up Study. Participants provided four stool samples—one pair collected 24–72 h apart and a second pair ~6 months later. Within-person taxonomic and functional variation was consistently lower than between-person variation over time. In contrast, metatranscriptomic profiles were comparably variable within and between subjects due to higher within-subject longitudinal variation. Metagenomic instability accounted for ~74% of corresponding metatranscriptomic instability. The rest was probably attributable to sources such as regulation. Among the pathways that were differentially regulated, most were consistently over- or under-transcribed at each time point. Together, these results suggest that a single measurement of the faecal microbiome can provide long-term information regarding organismal composition and functional potential, but repeated or short-term measures may be necessary for dynamic features identified by metatranscriptomics

Stromal Tumor Microenvironment in Chronic Lymphocytic Leukemia: Regulation of Leukemic Progression

Chronic Lymphocytic Leukemia (CLL), the most prevalent adult leukemia in western countries, which is highly heterogeneous with a very variable clinical outcome. Emerging evidence indicates that the stromal tumor microenvironment (STME) and stromal associated genes (SAG) play important roles in the pathogenesis and progression of CLL. However, the precise mechanisms by which STME and SAG are involved in this process remain unknown. In an attempt to explore the role of STME in this process, we examined the expression levels of stromal associated genes using gene expression profiling (GEP) of CLL cells from lymph nodes (LN) (n=15), bone marrow (BM) (n=18), and peripheral blood (PB) (n=20). Interestingly, LUM, MMP9, MYLK, ITGA9, CAV1, CAV2, FBN1, PARVA, CALD1, ITGB5 and EHD2 were found to be overexpressed while ITGB2, DLC1 and ITGA6 were under expressed in LN-CLL compared to BM-CLL and PB-CLL. This is suggestive of a role for LN-mediated TME in CLL cell survival/progression. Among these genes, expression of MYLK, CAV1 and CAV2 correlated with clinical outcome as determined by time to first treatment. Together, our studies show that members of the stromal signature, particularly in the CLL cells from lymph nodes, regulate CLL cell survival and proliferation and thus leukemic progression