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Abstract Induction regimens for multiple myeloma (MM) commonly include bortezomib, which has typically been administered twice weekly despite studies demonstrating comparable efficacy and less peripheral neuropathy (PN) with once-weekly bortezomib. We aimed to analyze the real-world prevalence and efficacy of once-weekly versus twice-weekly bortezomib regimens in newly diagnosed MM. We analyzed 2497 US patients aged 18–70 years treated with commercial first-line bortezomib using nationwide Flatiron Health electronic health record-derived data, including 910 (36.4%) patients who received twice-weekly and 1522 (63.2%) who received once-weekly bortezomib. Once-weekly bortezomib use increased over time, from 57.7% in 2017 to 73.1% in 2022. Multivariate analysis identified worsened performance status and more recent year of diagnosis with higher odds of receiving once-weekly bortezomib. Real-world progression-free survival (median 37.2 months with once-weekly versus 39.6 months with twice-weekly, p = 0.906) and overall survival (medians not reached in either cohort, p = 0.800) were comparable. PN rates were higher in patients receiving twice-weekly bortezomib (34.7% versus 18.5%, p

BackgroundDirect oral anticoagulants (DOACs) have comparable efficacy with low-molecular-weight heparin (LMWH) for the treatment of cancer-associated venous thromboembolism (VTE). Whether there is a mortality benefit of DOACs compared with warfarin in the management of VTE in cancer is not established.Methods and findingsUtilizing the United States' Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases from 2012 through 2016, we analyzed overall survival in individuals diagnosed with a primary gastric, colorectal, pancreas, lung, ovarian, or brain cancer and VTE who received a prescription of DOAC or warfarin within 30 days of VTE diagnosis. Patients were matched 1:2 (DOAC to warfarin) through exact matching for cancer stage and propensity score matching for age, cancer site, cancer stage, and time interval from cancer to VTE diagnosis. The analysis identified 4,274 patients who received a DOAC or warfarin for the treatment of VTE within 30 days of cancer diagnosis (1,348 in DOAC group and 2,926 in warfarin group). Patients were of median age 75 years and 56% female. Within the DOAC group, 1,188 (88%) received rivaroxaban, and 160 (12%) received apixaban. With a median follow-up of 41 months, warfarin was associated with a statistically significantly higher overall survival compared to DOACs (median overall survival 12.0 months [95% confidence interval (CI): 10.9 to 13.5] versus 9.9 months [95% CI: 8.4 to 11.2]; hazard ratio (HR) 0.85; 95% CI: 0.78 to 0.91; p < 0.001). Observed differences in survival were consistent across subgroups of cancer sites, cancer stages, and type of VTE. The study limitations include retrospective design with potential for unaccounted confounders along with issues of generalizability beyond the cancer diagnoses studied.ConclusionsIn this analysis of a population-based registry, warfarin was associated with prolonged overall survival compared to DOACs for treatment of cancer-associated VTE.

It is an age of the Internet and electronic media, and social media platforms are one of the most frequently used communication medium nowadays. But some people use these sites for malicious purpose and among those negative aspects "Cyberbullying" is prevalent. Cyberbullying is a form of bullying done through electronic means and is used to insult or harm others. Many researchers have proposed solutions and strategies to overcome this menace, but sarcasm is one aspect of it that still needs to be touched. This study aims to highlight previous researchers and to propose an approach to detect cyberbullying along with the element of sarcasm included in it. The results proved that SVM classifier performed better than other classifiers.

Internet of Things is a recent potential advancement in an IT arena, consists of multiple smart things (devices) which are connected through a physical network. Cisco incorporation predicts that IoT network will connect 50 billion devices by 2020. Most of the industries are adopting IoT technology and because of its fast spreading, immense adoption and deployment current authentication mechanisms have serious disadvantages. For numerous reasons the security issues are the major hurdle in adoption and deployment of IoT on a large scale since it is highly vulnerable to attacks. In this paper we propose a Blockchain based authentication mechanism i.e. Ethereum which is a public blockchain as it has emerged as a technology that possess great capabilities of providing secure authentication, management and access control for IoT devices in a decentralized, trusty and flexible manner by creating a secure environment where the devices can identify and trust each other and only authenticated users are given permission to access them.

Muhammad Adeel,1 Muhammad Asif,1 Muhammad Naeem Faisal,2 Muhammad Hasanain Chaudary,3 Muhammad Sheraz Malik,4 Muhammad Khalid5 1Department of Computer Science, Faculty of Science, National Textile University, Faisalabad, Punjab, Pakistan; 2Faculty of Veterinary Science, Institute of Pharmacy, Physiology, and Pharmacology, University of Agriculture, Faisalabad, Punjab, Pakistan; 3Department of Computer Science, COMSATS University, Islamabad, Lahore Campus, Lahore, Punjab, Pakistan; 4Department of Information Technology, Government College University, Faisalabad, Punjab, Pakistan; 5Oncology Department, Faisalabad Medical University, Allied Hospital, Faisalabad, Punjab, Pakistan Purpose: This retrospective study presents a comparative analysis of the overall survival and toxicities, as side effects, of docetaxel plus cyclophosphamide (TC) and doxorubicin plus cyclophosphamide (AC). The study measured their efficacies during adjuvant chemotherapy, treating Pakistani breast cancer patients by validating the results obtained, with the published analysis of the same treatment given to US patients.Patients and methods: Between June 2015 and September 2017, for four chemotherapy cycles, 189 patients out of 358 received TC (75 mg/m2 of docetaxel, 600 mg/m2 of cyclophosphamide) and 169 were treated with AC (60 mg/m2 of doxorubicin, 600 mg/m2 of cyclophosphamide). On the basis of using pathological markers to assess patients, toxicities, as side effects, (due to docetaxel, doxorubicin, and cyclophosphamide) were listed in the database of this study. Common factors with respect to common terminology criteria for adverse events version 5.0 and side effects listed in MedlinePlus, NIH US database, and from the database of this study were then separated to be included in comparison for this study. Statistically, chi-squared test was used at α=0.05.Results: There was no statistically significant difference between the proportions of patients with vomiting, extreme tiredness, diarrhea, mild anemia, stability, and overall survival because P-value >0.05. However, AC remained less toxic (P-value

Globally, the surge in disease and urgency in maintaining social distancing has reawakened the use of telemedicine/telehealth. Amid the global health crisis, the world adopted the culture of online consultancy. Thus, there is a need to revamp the conventional model of the telemedicine system as per the current challenges and requirements. Security and privacy of data are main aspects to be considered in this era. Data-driven organizations also require compliance with regulatory bodies, such as HIPAA, PHI, and GDPR. These regulatory compliance bodies must ensure user data privacy by implementing necessary security measures. Patients and doctors are now connected to the cloud to access medical records, e.g., voice recordings of clinical sessions. Voice data reside in the cloud and can be compromised. While searching voice data, a patient’s critical data can be leaked, exposed to cloud service providers, and spoofed by hackers. Secure, searchable encryption is a requirement for telemedicine systems for secure voice and phoneme searching. This research proposes the secure searching of phonemes from audio recordings using fully homomorphic encryption over the cloud. It utilizes IBM’s homomorphic encryption library (HElib) and achieves indistinguishability. Testing and implementation were done on audio datasets of different sizes while varying the security parameters. The analysis includes a thorough security analysis along with leakage profiling. The proposed scheme achieved higher levels of security and privacy, especially when the security parameters increased. However, in use cases where higher levels of security were not desirous, one may rely on a reduction in the security parameters.

The macula is an oval-shaped area near the center of the human retina, and at its center, there is a small pit known as the fovea. The fovea contains large concentrations of cone cells and is responsible for sharp, colored vision. Macular disorders are the group of diseases that damage the macula, resulting in blurred vision or even blindness. Macular edema (ME), one of the most common types of macular disorder, is caused by fluid accumulation beneath the macula. In this paper, we present an automated system for the detection of ME from fundus images. We introduce a new automated system for the detailed grading of the severity of disease using knowledge of exudates and maculae. A new set of features is used along with a minimum distance classifier for accurate localization of the fovea, which is important for the grading of ME. The proposed system uses different hybrid features and support vector machines for segmentation of exudates. The detailed grading of ME—as both clinically significant ME and non-clinically significant ME—is done using localized foveae and segmented exudates. The proposed algorithm is validated using public and local data sets. We have achieved an average accuracy of 96.1% in the detection and grading of ME with our proposed method.

Cancer associated with smoking and drinking remains a serious health problem worldwide. The survival of patients is very poor due to the lack of effective early biomarkers. FOXM1 overexpression is linked to the majority of human cancers but its mechanism remains unclear in head and neck squamous cell carcinoma (HNSCC).FOXM1 mRNA and protein expressions were investigated in four independent cohorts (total 75 patients) consisting of normal, premalignant and HNSCC tissues and cells using quantitative PCR (qPCR), expression microarray, immunohistochemistry and immunocytochemistry. Effect of putative oral carcinogens on FOXM1 transcriptional activity was dose-dependently assayed and confirmed using a FOXM1-specific luciferase reporter system, qPCR, immunoblotting and short-hairpin RNA interference. Genome-wide single nucleotide polymorphism (SNP) array was used to 'trace' the genomic instability signature pattern in 8 clonal lines of FOXM1-induced malignant human oral keratinocytes. Furthermore, acute FOXM1 upregulation in primary oral keratinocytes directly induced genomic instability. We have shown for the first time that overexpression of FOXM1 precedes HNSCC malignancy. Screening putative carcinogens in human oral keratinocytes surprisingly showed that nicotine, which is not perceived to be a human carcinogen, directly induced FOXM1 mRNA, protein stabilisation and transcriptional activity at concentrations relevant to tobacco chewers. Importantly, nicotine also augmented FOXM1-induced transformation of human oral keratinocytes. A centrosomal protein CEP55 and a DNA helicase/putative stem cell marker HELLS, both located within a consensus loci (10q23), were found to be novel targets of FOXM1 and their expression correlated tightly with HNSCC progression.This study cautions the potential co-carcinogenic effect of nicotine in tobacco replacement therapies. We hypothesise that aberrant upregulation of FOXM1 may be inducing genomic instability through a program of malignant transformation involving the activation of CEP55 and HELLS which may facilitate aberrant mitosis and epigenetic modifications. Our finding that FOXM1 is upregulated early during oral cancer progression renders FOXM1 an attractive diagnostic biomarker for early cancer detection and its candidate mechanistic targets, CEP55 and HELLS, as indicators of malignant conversion and progression.

Geochemical and sedimentological analyses and C-14 dating of four cores from Erdek and Bandırma Bays were performed to evaluate the metal pollution, history and sources, and content in the southern Sea of Marmara (SoM) caused by industrial, agricultural and domestic activities during the sediment deposition. The selected elements' pollution (Al, Fe, Mn, As, Co, Cr, Cu, Hg, Ni, Pb, V and Zn) data were evaluated using contamination factor (CF) and pollution load index (PLI). The sedimentary succession in all cores consists mainly of clay (9–96%), silt (1–78%) and sand (0.1–20%) with small amounts of gravel (0.1–7%). The results of CF and PLI reveal that the upper 20 cm core sediments in Erdek Bay were contaminated with Hg (0.07–1.1 mg/kg), Pb (4–72 mg/kg) and Zn (12–255 mg/kg) by both anthropogenic and lithogenic input via the Biga and Gönen streams. Furthermore, the upper 20 cm of MD72 and BK1 core sediments were moderately polluted with As, Cu, Hg, Pb and Zn caused by the discharge of untreated industrial wastewater and domestic sewage from the surrounding area of Bandırma Bay. Moreover, lithogenic Pb-Zn was transported to Erdek Bay by Biga and Gönen streams from the Pb-Zn mineralized zones in the southern SoM drainage area. C-14 dating reveals that As, Hg, Pb and Zn contamination in the study area was started about 400–500 years before the present based on preliminary sedimentation rate estimates and has increased intensely in the last century. Our work is a significant effort to help the environment protection agency or other stakeholders draw a framework to solve this emerging challenge from sewage and wastewater treatment plants. [ABSTRACT FROM AUTHOR]

Background Direct oral anticoagulants (DOACs) have comparable efficacy with low-molecular-weight heparin (LMWH) for the treatment of cancer-associated venous thromboembolism (VTE). Whether there is a mortality benefit of DOACs compared with warfarin in the management of VTE in cancer is not established. Methods and findings Utilizing the United States' Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases from 2012 through 2016, we analyzed overall survival in individuals diagnosed with a primary gastric, colorectal, pancreas, lung, ovarian, or brain cancer and VTE who received a prescription of DOAC or warfarin within 30 days of VTE diagnosis. Patients were matched 1:2 (DOAC to warfarin) through exact matching for cancer stage and propensity score matching for age, cancer site, cancer stage, and time interval from cancer to VTE diagnosis. The analysis identified 4,274 patients who received a DOAC or warfarin for the treatment of VTE within 30 days of cancer diagnosis (1,348 in DOAC group and 2,926 in warfarin group). Patients were of median age 75 years and 56% female. Within the DOAC group, 1,188 (88%) received rivaroxaban, and 160 (12%) received apixaban. With a median follow-up of 41 months, warfarin was associated with a statistically significantly higher overall survival compared to DOACs (median overall survival 12.0 months [95% confidence interval (CI): 10.9 to 13.5] versus 9.9 months [95% CI: 8.4 to 11.2]; hazard ratio (HR) 0.85; 95% CI: 0.78 to 0.91; p < 0.001). Observed differences in survival were consistent across subgroups of cancer sites, cancer stages, and type of VTE. The study limitations include retrospective design with potential for unaccounted confounders along with issues of generalizability beyond the cancer diagnoses studied. Conclusions In this analysis of a population-based registry, warfarin was associated with prolonged overall survival compared to DOACs for treatment of cancer-associated VTE., Author(s): Adeel M. Khan 1, Thita Chiasakul 1,2, Robert Redd 3, Rushad Patell 1, Ellen P. McCarthy 4,5, Donna Neuberg 3, Jeffrey I. Zwicker 1,* Introduction Cancer-associated thromboembolism (CAT) is [...]

Abstract Recently, the complete landscape of three-family supersymmetric Pati-Salam models from intersecting D6-branes on a type IIA T 6 / ℤ 2 × ℤ 2 $$ {\mathbbm{T}}^6/\left({\mathbb{Z}}_2\times {\mathbb{Z}}_2\right) $$ orientifold has been enumerated consisting of 33 independent models with distinct gauge coupling relations at the string scale. Here, we study the phenomenology of all such models by providing the detailed particle spectra and the analysis of the possible 3-point and the 4-point Yukawa interactions in order to accommodate all standard-model fermion masses and mixings. We find that only 17 models contain viable Yukawa textures to explain quarks masses, charged-leptons’ masses, neutrino-masses, quarks’ mixings and leptons’ mixings. These viable models split into four classes, viz. a single model with 3 Higgs fields from the bulk and sixteen models with either 6, 9 or 12 Higgs from the N $$ \mathcal{N} $$ = 2 sector. The models perform successively better with the increasing number of Higgs pairs. Remarkably, the class of models with 12 Higgs naturally predicts the Dirac-type neutrino masses in normal ordering consistent with both the experimental constraints as well as the bounds from the swampland program.

Abstract Background Daphnia galeata is a suitable model organism for investigating predator-induced defense. Genes and pathways exhibiting differential expression between fish kairomone-treated and untreated groups in D. galeata have been identified. However, understanding of the significance of alternative splicing, a crucial process of the regulation of gene expression in eukaryotes, to this mechanism remains limited. This study measured life-history traits and conducted short-read RNA sequencing and long-read isoform sequencing of two Korean D. galeata genotypes (KB1 and KE2) to uncover the genetic mechanism underlying their phenotypic plasticity under predation stress. Results KB1 exhibited strategies to enhance fertility and decrease body length when exposed to fish kairomones, while KE2 deployed an adaptive strategy to increase body length. Full-length transcriptomes from KB1 and KE2 yielded 65,736 and 57,437 transcripts, respectively, of which 32 differentially expressed transcripts (DETs) were shared under predation stress across both genotypes. Prominent DETs common to both genotypes were related to energy metabolism and the immune system. Additionally, differential alternative splicing (DAS) events were detected in both genotypes in response to fish kairomones. DAS genes shared between both genotypes may indicate their significant role in the post-transcriptional stress response to fish predation. Calpain-3, involved in digestion and nutrient absorption, was identified as a DAS gene in both genotypes when exposed to fish kairomones. In addition, the gene encoding thymosin beta, which is related to growth, was found to be a statistically significant DAS only in KB1, while that encoding ultraspiracle protein, also associated with growth, was only identified in KE2. Moreover, transcripts encoding proteins such as EGF-like domain-containing protein, vitellogenin fused with superoxide dismutase, and others were identified overlapping between DAS events and DETs and potentially elucidating their association with the observed phenotypic variation in each genotype. Conclusions Our findings highlight the crucial role of alternative splicing in modulating transcriptome landscape under predation stress in D. galeata, emphasizing the requirement for integrating gene expression and splicing analyses in evolutionary adaptation studies.