A Comparative Study for Methodologies and Algorithms Used In Colon Cancer Diagnoses and Detection

Colon cancer is also referred to as colorectal cancer; it is a kind of cancer that starts with colon damage to the large intestine in the last section of the digestive tract. Elderly people typically suffer from colon cancer, but this may occur at any age. It normally starts as a little, noncancerous (benign) mass of cells named polyps that structure within the colon. After a period of time these polyps can turn into advanced malignant tumors that attack the human body and some of these polyps can become colon cancers. So far, no concrete causes have been identified and the complete cancer treatment is very difficult to be detected by doctors in the medical field. Colon cancer often has no symptoms in an early stage so detecting it at this stage is curable but colorectal cancer diagnosis in the final stages (stage IV), gives it the opportunity to spread into different pieces of the body, which are difficult to treat successfully, and the person\u27s opportunities of survival become much lower. False diagnosis of colorectal cancer which means wrong treatment for patients with long-term infections and they will be suffering from colon cancer this causing the death for these patients. Also, cancer treatment needs more time and a lot of money. This paper provides a comparative study for methodologies and algorithms used in the colon cancer diagnoses and detection this can help for proposing a prediction for risk levels of colon cancer disease using CNN algorithm of deep learning (Convolutional Neural Networks Algorithm)

Design, synthesis, molecular modeling and biological evaluation of novel diaryl heterocyclic analogs as potential selective cyclooxygenase-2 (COX-2) inhibitors

AbstractNew series of 3,4-diaryl-2-thioxoimidazolidin-4-ones and 3-alkylthio-4,5-diaryl-4H-1,2,4-triazoles were designed, synthesized and evaluated for their activity as anti-inflammatory agents. Compounds 20, 21, 23 and 34 are highly selective inhibitors of COX-2 enzyme at a concentration of 100mM relative to celecoxib, the standard reference. (±)-3-(4-Phenoxy-phenyl)-5-phenyl-2-thioxoimidazolidin-4-ones 23 exhibited the most active anti-inflammatory agent

Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

IL-4 downregulates BCL6 to promote memory B cell selection in germinal centers

Thesis (Ph.D.)--University of Washington, 2023Germinal center (GC)-derived memory B cells (MBCs) play a pivotal role in humoral immunity by differentiating into protective antibody-secreting cells upon re-infection. Despite extensive research focused on GC formation and the cellular interactions occurring within the GC microenvironment, the precise signals which regulate MBC selection and exit remain incompletely understood. In these studies, we focus on the role of interleukin-4 (IL-4) in the GC using murine blood-stage Plasmodium infections as a model of for a type 1 immune response. Our findings demonstrate that IL-4 signaling can trigger the selection and exit of GC B cells by modulating the expression of BCL6, the primary transcription factor within the GC. Specifically, we show that IL-4 induces negative autoregulation of BCL6, leading to a loss in expression of this anti-apoptotic factor within GC B cells. Consequently, in the presence of excess IL-4, there is increased GC B cell death and a loss of selection stringency. Furthermore, we demonstrate that in the absence of IL-4-mediated downregulation of BCL6, B cells with lower affinity can persist within the GC and contribute to the MBC pool. This observation highlights the critical role of IL-4-mediated downregulation of BCL6 in maintaining selection stringency and affinity maturation within the MBC population. By elucidating the role of IL-4 in modulating the fate of GC B cells, we have demonstrated the significance of IL-4 signaling in shaping the dynamics of the GC selection and subsequent memory formation. The importance of both GCs and memory formation are further underscored in chapter 3, in which we analyze the B cell response generated by both protein nanoparticle vaccines and by natural infection with SARS-CoV-2. As the formation of class-switched MBCs and LLPCs are the primary correlate of protection for vaccination, our finding that a nanoparticle displaying the receptor binding domain of SARS-CoV-2 can elicit the formation of a robust GC with class-switched B cells was very promising for the future of nanoparticle vaccines. Collectively, these findings offer novel insights into the mechanisms underlying MBC selection and affinity maturation within the GC. Through the identification of IL-4 as a negative regulator of BCL6 expression and its impact of GC B cell survival, our study advances the current understanding of how the immune system maintains an optimal balance between selection stringency and the generation of diverse MBC populations. Further research in this area will likely explore additional signaling pathways and molecular players involved in the complex network of interactions governing GC-derived MBC selection, and ultimately will contribute to the development of strategies aimed at enhancing immune responses and vaccine efficacy

Site-Directed Mutagenesis to Improve Sensitivity of a Synthetic Two-Component Signaling System

Two-component signaling (2CS) systems enable bacterial cells to respond to changes in their local environment, often using a membrane-bound sensor protein and a cytoplasmic responder protein to regulate gene expression. Previous work has shown that Escherichia coli’s natural EnvZ/OmpR 2CS could be modified to construct a light-sensing bacterial photography system. The resulting bacterial photographs, or “coliroids,” rely on a phosphotransfer reaction between Cph8, a synthetic version of EnvZ that senses red light, and OmpR. Gene expression changes can be visualized through upregulation of a LacZ reporter gene by phosphorylated OmpR. Unfortunately, basal LacZ expression leads to a detectable reporter signal even when cells are grown in the light, diminishing the contrast of the coliroids. We performed site-directed mutagenesis near the phosphotransfer site of Cph8 to isolate mutants with potentially improved image contrast. Five mutants were examined, but only one of the mutants, T541S, increased the ratio of dark/light gene expression, as measured by β-galactosidase activity. The ratio changed from 2.57 fold in the starting strain to 5.59 in the T541S mutant. The ratio decreased in the four other mutant strains we examined. The phenotype observed in the T541S mutant strain may arise because the serine sidechain is chemically similar but physically smaller than the threonine sidechain. This may minimally change the protein’s local structure, but may be less sterically constrained when compared to threonine, resulting in a higher probability of a phosphotransfer event. Our initial success pairing synthetic biology and site-directed mutagenesis to optimize the bacterial photography system’s performance encourages us to imagine further improvements to the performance of this and other synthetic systems, especially those based on 2CS signaling

Robotic Surgery in Gynecology Critical Review

Minimally invasive surgery (MIS) can be considered as the best surgical innovation in the course of recent years. It changed surgical practice with all well demonstrated benefits over conventional open a surgical procedure: reduced surgical trauma and incision related complications, like surgical site infections, postoperative pain, hernia, decreased hospital stay, and improved surgical outcome. Regardless, capability in MIS can be technically challenging as conventional laparoscopy is related with several constraints as the two-dimensional (2D) screen decrease in-depth perception, camera instability, restricted scope of movement, and steep learning curves.The surgeon has a low force feedback, which permits straightforward motions, respect for tissues, and more effective treatment of complications. Since the 1980s, many PC sciences and robotic projects have been set up to beat the challenges experienced with regular laparoscopy, to increase the surgeon's abilities, accomplish exactness and increased accuracy during conventional laparoscopy, and work with widespread of MIS. Surgical instruments are coordinated by haptic interfaces that replicate and filter hand movements. Robotically assisted technology offers benefits that incorporate worked on three-dimensional stereoscopic vision, wristed instruments that further develop ability, and tremor cancelling software that improves surgical precision

3D Bioprinting for Tissue Engineering Application Review

Three-dimensional (3D) printing (rapid prototyping or additive fabricating innovations) has gotten significant consideration in different fields in the course of recent many years. Tissue engineering uses of 3D bioprinting, specifically, have attracted the attention of numerous researchers. 3D platforms delivered by the 3D bioprinting of biomaterials (bio-inks) empower the recovery and rebuilding of different tissues and organs. These 3D bioprinting methods are helpful for creating platforms for biomedical and regenerative medication and tissue engineering applications, allowing quick production with high-accuracy and control over size, porosity, and shape. In this review, we present an assortment of tissue designing applications to make bones, vascular, skin, ligament, and neural structures utilizing an assortment of 3D bioprinting strategies

Digital Health During COVID-19 Pandemic: Challenges and opportunities Review

Corona virus pandemic caused an enormous effect on medical care, public activity, and economies on a worldwide scale. Clearly, technology has a vital role to empower omnipresent and available digital health services in pandemic conditions just as against “reappearance” of COVID-19 disease in a post-pandemic period. Likewise, 5G systems and 5G-empowered e-health arrangements are principal. This paper features philosophies to adequately use 5G for e-health use cases and its job to empower significant digital healthcare services. It's anything but a comprehensive conversation of the implementation issues, potential cures and future research bearings for 5G to lighten the health challenges related to COVID-19