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BackgroundNew highly efficacious direct-acting antiviral (DAA) therapies are available to treat chronic hepatitis C viral (HCV) infection. Real-world, patient-centered data on harms and benefits associated with these therapies are needed.MethodsPROP UP is a multi-center prospective observational study that plans to enroll 1600 patients starting treatment with recently-approved DAA regimens. Informed by extensive input from a HCV patient engagement group who prioritized outcomes most important to them, patient-reported outcomes will be characterized using surveys at five time points: Baseline (T1), treatment week 4 (T2), end of treatment (T3), 12weeks post-treatment (T4), 12months post-treatment (T5).Outcomes(1) Changes in side effects, functioning, pre-existing conditions, and out-of-pocket costs during therapy (T1 vs T2/T3); (2) Medication adherence in relation to a history of mental health/substance abuse, treatment regimens, pill burden, reasons for missed doses, and cure rates; (3) Short term impact of cure on functioning and amelioration of symptoms (T1 vs T4); (4) Long-term treatment harms or benefits of cure on symptoms, side effects, pre-existing conditions, and functioning (T1 vs T5). Similarities between regimens will be examined where comparisons are appropriate and meaningful.ConclusionPROP UP complements previous clinical trials by focusing on patient-reported outcomes in a representative sample of patients treated in clinical practice, by collaborating with a patient engagement group, by characterizing the experiences of vulnerable subgroups, and by investigating long-term harms and benefits of treatments. PROP UP is designed to provide novel and detailed information to support informed decision-making for patients and providers contemplating HCV treatment (PCORI CER-1408-20,660; NCT02601820).

The present contribution to the Regional Editors themed issue offers a concise yet focused overview of some of the key technical and scientific issues, as well as of current trends and future challenges, related to the broad discipline of environmental geotechnics in the US region. Particular attention is devoted to current policy and societal drivers as well as future professional and research capacity requirements in critical areas such as innovative recycling and improvement of compost, construction and geologic materials; solid waste management, landfilling and geoenvironmental remediation techniques; and crucial geotechnical engineering aspects of renewable energy production, storage and distribution.

Introduction/Objective. Pathologic fractures are devastating complications in metastatic bone disease. Treatment of these condition varies, and includes systemic therapies and surgical interventions. Lack of evidence still exists for standardized care. The aim of this study is to analyze radiological healing response and clinical outcomes after intramedullary nailing (IMN) and adjuvant radiotherapy in complete pathologic fractures of femur or humerus Methods. A total of 19 patients who presented with pathological fracture were retrospectively reviewed. Data regarding demographic characteristics, clinical outcomes and radiologic images were obtained from hospital records. All patients in this cohort were treated with closed, unreamed IMN and adjuvant radiation treatment. Results. Pain relief and full range of motion was obtained in all patients. The mean postoperative Musculoskeletal Tumor Society scores at last follow-up were 69% (range 50–85). All patients demonstrated complete radiographic healing between 2 and 6 months. Only one patient required reoperation for refracture at the tip of the nail which was revised with a longer nail. Conclusion. Our study demonstrated that pathologic fractures managed with closed unreamed IMN and adjuvant multifractional 20 Gy dose radiotherapy yielded good clinical outcomes with complete radiologic response regardless of patient’s life expectancy, adjuvant treatments and overall condition. Closed unreamed IMN was also associated with decreased surgical time in these high-risk patients.

This study presents a sustainability assessment of geothermal heating and cooling system of three buildings at the University of Illinois at Chicago - Grant, Lincoln, and Douglas Halls based upon the triple bottom line sustainability framework and presents a comparison between geothermal and conventional heating and cooling systems. Life cycle assessment (LCA) was performed to evaluate and quantify the environmental impacts for both geothermal and conventional systems. Similarly, economic impacts were evaluated by making a comparison between direct and indirect costs of both systems. Indirect costs were calculated using Stepwise 2006 incorporated in monetized LCA and compared that cost with social cost of carbon. Social impacts were quantified using Social Sustainability Evaluation Matrix (SSEM) which covers four major dimensions of society: social-individual, socio-institutional, socio-economic, and socio-environmental. An overall sustainability index for geothermal system and conventional system was calculated by evaluating environmental, economic, and social impacts using Integrated Value Model for Sustainability Assessment (MIVES) methodology. The results show that the geothermal heating and cooling system is more sustainable and environmentally friendly than the conventional system.

This study introduces a silver-catalyzed method for the efficient and regioselective synthesis of pyrano heterocycles, utilizing readily available alcohols and water as nucleophiles. The method demonstrates high efficiency, delivering excellent yields and selectivity, and is scalable to gram quantities while maintaining broad functional group tolerance. Notably, the synthesized pyrano[3,4- c ]quinolines were successfully transformed into diverse samoquasine A derivatives, underscoring the method's applicability in natural product synthesis. This work represents a significant advancement in pyrano heterocycle synthesis, offering a practical route to valuable compounds with potential applications in pharmaceutical and chemical research.

Background: The accuracy of current criteria for ruling out large oesophageal varices (LEV) and other endoscopic lesions of portal hypertension (PH) may be compromised by obesity and MASLD/MASH., Aims: In the US multicentre SHUNT-V study, we evaluated the disease severity index (DSI) for detecting LEV and other lesions of PH at endoscopy., Methods: Subjects were adults with compensated cirrhosis scheduled for endoscopy to screen for varices. DSI was calculated from clearances of labelled cholates after oral and intravenous administration. DSI ≤ 18.3 was evaluated as a cut-off for ruling out LEV with acceptance criteria of negative likelihood ratio < 0.52 and sensitivity > 85%., Results: SHUNT-V enrolled 306 subjects; 275 had both DSI and endoscopy, and 238 had Child-Pugh A cirrhosis (52.1% MASLD/MASH, 25.2% chronic hepatitis C and 15.6% alcoholic liver disease; 87% were overweight, 64% were obese and 54% had diabetes). AUROCs for DSI ranged from 0.81 to 0.82 for LEV and 0.79 to 0.80 for all significant PH lesions. DSI 18.3 had sensitivity 96.3%-100% for LEV and 97.3%-100% for all significant PH lesions. If DSI ≤ 18.3 were used as the sole determinant to defer EGD, 27%-35% of EGDs could have been avoided with 0%-3.7% of LEV and 0%-2.7% of all significant PH lesions missed., Conclusions: HepQuant DSI predicts the likelihood of LEV and significant PH lesions across a spectrum of patient characteristics and disease aetiologies. DSI, based on liver function and portal-systemic shunting, can aid in the decision to defer endoscopy for varices in patients with Child-Pugh A cirrhosis., Trial Registration: The SHUNT-V study was registered at ClinicalTrials.gov (NCT03583996)., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background and Aims: Hepatocellular carcinoma (HCC) risk stratification is an urgent unmet need for cost-effective HCC screening and early detection in patients with cirrhosis to improve poor HCC prognosis., Methods: Molecular (Prognostic Liver Secretome signature with alpha-fetoprotein) and clinical (aMAP score) variable-based scores were integrated to develop PAaM, which was subsequently validated in two phase 3 biomarker validation studies: the statewide Texas HCC Consortium (THCCC) and nationwide HCC Early Detection Strategy (HEDS) prospective cohorts, following the prospective specimen collection, retrospective blinded evaluation (PRoBE) design. The associations between baseline PAaM and incident HCC were assessed using Fine-Gray regression, with overall death and liver transplantation as competing events., Results: Of 2,156 cirrhosis patients in THCCC, PAaM identified 404 (19%) high-risk, 903 (42%) intermediate-risk, and 849 (39%) low-risk patients with annual HCC incidence rates of 5.3%, 2.7%, and 0.6%, respectively. Compared to low-risk patients, high- and intermediate-risk groups had sub-distribution hazard ratios (sHRs) for incident HCC of 7.51 (95% confidence interval [CI], 4.42-12.8) and 4.20 (95%CI, 2.52-7.01), respectively. Of 1,328 cirrhosis patients in HEDS, PAaM identified 201 (15%) high-risk, 540 (41%) intermediate-risk, and 587 (44%) low-risk patients, with annual HCC incidence rates of 6.2%, 1.8%, and 0.8%, respectively. High- and intermediate risk groups were associated with sHRs for incident HCC of 6.54 (95%CI, 3.85-11.1) and 1.77 (95%CI, 1.02-3.08), respectively. Subgroup analysis showed robust risk stratification across HCC etiologies, including metabolic dysfunction-associated steatotic liver disease (MASLD) and cured hepatitis C infection., Conclusion: PAaM enables accurate HCC risk stratification in patients with cirrhosis from contemporary etiologies., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Acute liver failure (ALF) and acute-on-chronic liver (ACLF) are distinct phenotypes of liver failure and, thus, need to be compared and contrasted for appropriate management. There has been a significant improvement in the outcomes of these patients undergoing liver transplantation (LT). Survival post-LT for ALF and ACLF ranges between 90% and 95% and 80% and 90% at 1 year, futility criteria have been described in both ALF and ACLF where organ failures define survival. Plasma exchange and continuous renal replacement therapy may serve as bridging therapies. Identifying the futility of LT is as necessary as the utility of LT in patients with ALF and ACLF. The role of regenerative therapies such as granulocyte colony-stimulating factors in ACLF and hepatocyte and xenotransplantation in both conditions remains uncertain. Measures to increase the donor pool through increasing deceased donor transplants in Asian countries, living donations in Western countries, auxiliary liver transplants, and ABO-incompatible liver transplants are necessary to improve the survival of these patients. In this review, we discuss the similarities and differences in clinical characteristics and the timing and outcomes of LT for ALF and ACLF, briefly highlighting the role of bridging therapies and providing an overview of recent advances in the management of ALF and ACLF., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: Exposomes are critical drivers of carcinogenesis. However, how they modulate tumor behavior remains unclear. Extensive clinical data link cigarette smoke as a key exposome that promotes aggressive tumors, higher rates of metastasis, reduced response to chemoradiotherapy, and suppressed anti-tumor immunity. We sought to determine whether smoke itself can modulate aggressive tumor behavior in head and neck squamous cell carcinoma (HNSCC) through reprogramming the cellular reductive state., Experimental Design: Using established human and murine HNSCC cell lines and syngeneic mouse models, we utilized conventional western blotting, steady state and flux metabolomics, RNA sequencing, quantitative proteomics and flow cytometry to analyze the impact of smoke exposure on HNSCC tumor biology., Results: Cigarette smoke persistently activated Nrf2 target genes essential for maintenance of the cellular reductive state and survival under conditions of increased oxidative stress in HNSCC regardless of HPV status. In contrast to e-cigarette vapor, conventional cigarette smoke mobilizes cellular metabolism toward oxidative stress adaptation, resulting in development of cross-resistance to cisplatin. In parallel, smoke exposure modulates both expression of PDL1 and the secretory phenotype of HNSCC cells through activation of NF-κB resulting in an altered tumor immune microenvironment (TIME) in syngeneic mouse models and altered PBMC differentiation that includes downregulated expression of antigen presentation and costimulatory genes in myeloid cells., Conclusion: Cigarette smoke exposome is a potent activator of the Nrf2 pathway and is a likely primary trigger for the tripartite phenotype of aggressive HNSCC consisting of: 1) reduced chemotherapy sensitivity, 2) enhanced metastatic potential and 3) suppressed anti-tumor immunity., Statement of Significance: The smoke exposome drives aggressive tumor behavior, treatment resistance and suppressed immunity through coordinated metabolic reprogramming. Successfully targeting this adaptation is critical to improving survival in smokers with head and neck cancer.

Background and Objectives: This study aimed to investigate the effect of zinc phosphate (ZnP) cement, glass ionomer cement (GIC), and nano-integrated bio-ceramic (NIB) cement on mineralization when placed in contact with bone tissue-forming cells. Materials and Methods: ZnP cement, GIC, and NIB cement were divided into direct and indirect groups. A total of 72 cement pellets (24 pellets of each test sample) of 3 × 1 mm (width × height) were prepared using polytetrafluoroethylene molds. A total of 3 sample groups were demarcated using 96- cell well culture plates. In the control group, 24 wells were filled with mineralized osteoblasts and 1 µL of gingival crevicular fluid (GCF). In test group 1, to show a direct effect, 36 samples were plated with mineralized osteoblasts and 1 µL GCF for 24 h; the cells were directly exposed to cement pellets. A total of 36 samples were immersed in GCF for 24 h; later the supernatant was transferred to the mineralized osteoblasts to demonstrate an indirect effect in test group 2. To assess the mineralization, osteoblasts were stained with alizarin red and later observed under an inverted phase-contrast microscope. Data were analyzed using the statistical package for social sciences. An independent t-test compared the direct and indirect effects of the ZnP cement, GIC, NIB cement, and control groups on the mineralization of osteoblasts derived from hDPCs. Results: A statistically significant difference was observed between the ZnP cement, GIC, and NIB cement groups ( p < 0.05). ZnP cement exhibited a moderate, NIB cement the least harmful effect, and GIC showed the most harmful effect on the mineralization of osteoblast cells. Conclusions: The biocompatibility of dental luting cements is an important aspect that clinicians should consider during their selection. Nano-integrated bio-ceramic cement showed the least negative effect on the mineralization of osteoblast cells which is beneficial for the cementation of cement-retained implant prostheses. However, further studies are needed to evaluate osteoblast and osteoclast activity in vivo.

Leprosy in children is considered as an indicator of active disease transmission in the community. We report about a seven-year-old male from Telangana, India, with anesthetic skin lesions and familial leprosy history. Clinical examination revealed multiple, dry, scaly, hypopigmented, well-defined, raised punched out anesthetic skin lesions all over the body with both ulnar nerves enlarged. On clinical and laboratory examination, the child was diagnosed with borderline-borderline (BB), multibacillary (MB) leprosy, and Type-1 reaction. The child received a weight-adjusted MB multidrug therapy regimen and corticosteroids for type-1 reactions. This case emphasizes the need for contact tracing and screening for early diagnosis of child leprosy to prevent complications like leprosy reactions which are the risk factors for disability., (Copyright© 2024 The Authors. Published by Tehran University of Medical Sciences.)

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is associated with significant morbidity and mortality. While liver transplantation is the definitive treatment, continuous terlipressin infusion for HRS-AKI may provide benefit and, as such, was assessed in a population composed of candidates for liver transplant (LT). Fifty hospitalized LT-eligible patients with HRS-AKI received a single bolus followed by continuous terlipressin infusion. Acute-on-chronic liver failure grade 3, serum creatinine (SCr)>5.0 mg/dL, or Model for End-Stage Liver Disease (MELD) ≥35 were exclusions. Fifty hospitalized patients who received midodrine and octreotide or norepinephrine for HRS-AKI served as a historical comparator cohort. Complete response (CR) was defined as a ≥30% decrease in SCr with end-of-treatment (EOT) SCr≤1.5, partial response as a ≥30% decrease in SCr with EOT SCr>1.5, and nonresponse as a <30% decrease in SCr. CR rate was significantly higher in the terlipressin cohort compared to the historical cohort (64% vs. 16%, p <0.001). Survival, while numerically higher in those who received terlipressin, was statistically similar (D30: 94% vs. 82%, p =0.12; D90: 78% vs. 68%, p =0.37). Renal replacement therapy (RRT) was more common among terlipressin NR than CR and PR (70% vs. 3% vs. 13%, p < 0.001). EOT MELD and SCr were significantly lower within terlipressin cohort (MELD: 19 vs. 25, SCr: 1.4 vs. 2.1 mg/dL, p <0.001). Sixteen of 40 terlipressin-treated patients received LT-alone (terlipressin CR in 10/16). One patient on terlipressin had a hypoxic respiratory failure that responded to diuretics; one possibly had drug-related rash. With continuous terlipressin infusion, a CR rate of 64% was observed with a favorable safety profile. Terlipressin use was associated with lower EOT MELD and SCr than the historical midodrine and octreotide/norepinephrine cohort; LT-alone was accomplished in a high proportion of complete terlipressin responders., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Posttransplant diabetes mellitus (PTDM) is a prevalent complication of liver transplantation and is associated with cardiometabolic complications. We studied the consequences of genetic effects of liver donors and recipients on PTDM outcomes, focusing on the diverse genetic pathways related to insulin that play a role in the development of PTDM. One thousand one hundred fifteen liver transplant recipients without a pretransplant diagnosis of type 2 diabetes mellitus (T2D) and their paired donors recruited from 2 transplant centers had polygenic risk scores (PRS) for T2D, insulin secretion, and insulin sensitivity calculated. Among recipients in the highest T2D-PRS quintile, donor T2D-PRS did not contribute significantly to PTDM. However, in recipients with the lowest T2D genetic risk, donor livers with the highest T2D-PRS contributed to the development of PTDM (OR [95% CI] = 3.79 [1.10-13.1], P = .035). Recipient risk was linked to factors associated with insulin secretion (OR [95% CI] = 0.85 [0.74-0.98], P = .02), while donor livers contributed to PTDM via gene pathways involved in insulin sensitivity (OR [95% CI] = 0.86 [0.75-0.99], P = .03). Recipient and donor PRS independently and collectively serve as predictors of PTDM onset. The genetically influenced biological pathways in recipients primarily pertain to insulin secretion, whereas the genetic makeup of donors exerts an influence on insulin sensitivity., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Health system resilience is a prerequisite for effectively managing cataclysmic events adversely affecting health outcomes. The COVID-19 pandemic reasserted the importance of having resilient health systems and called for a relook at the existing framework that measures health system resilience. Mixed methods were used in this study. The review started with the measurement of health systems resilience and its context. Ebola epidemic triggered the importance, hence our search focused on published literature from 2014 to 2021. Based on the review, a semi-structured tool was developed for key in-depth interviews of seven experts from different countries. The frameworks focused on climate change, disaster management, health systems, city-specific resilience, and e-resilience were reviewed. In-depth interviews highlighted that resilient health systems need to engage the private sector, priority areas like leadership and governance, health resources, and a unified agenda for global collaboration. From experts' point of view, the inherent nature of health systems to respond to shock was clearly defined as the resilient health system. Health systems resilience definition needs to be defined, based on which assessment indicators will be identified. Indicators need to evolve continuously and be able to measure resilience at sub-national, national, regional, and global levels., Competing Interests: The authors have declared that no competing interest exist., (Copyright: © 2024 Dsouza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In tumors with WT p53, alternate mechanisms of p53 inactivation are reported. Here, we have identified a long noncoding RNA, PITAR ( p 53 I nactivating T RIM28 A ssociated R NA), as an inhibitor of p53. PITAR is an oncogenic Cancer/testis lncRNA and is highly expressed in glioblastoma (GBM) and glioma stem-like cells (GSC). We establish that TRIM28 mRNA, which encodes a p53-specific E3 ubiquitin ligase, is a direct target of PITAR. PITAR interaction with TRIM28 RNA stabilized TRIM28 mRNA, which resulted in increased TRIM28 protein levels and reduced p53 steady-state levels due to enhanced p53 ubiquitination. DNA damage activated PITAR , in addition to p53, in a p53-independent manner, thus creating an incoherent feedforward loop to inhibit the DNA damage response by p53. While PITAR silencing inhibited the growth of WT p53 containing GSCs in vitro and reduced glioma tumor growth in vivo, its overexpression enhanced the tumor growth in a TRIM28 -dependent manner and promoted resistance to Temozolomide. Thus, we establish an alternate way of p53 inactivation by PITAR , which maintains low p53 levels in normal cells and attenuates the DNA damage response by p53. Finally, we propose PITAR as a potential GBM therapeutic target., Competing Interests: SJ, MM, SM, BG, KP, LK, NJ, AC, VS, CK No competing interests declared, KS Reviewing editor, eLife, (© 2023, Jana et al.)

Background & Aims: Better surveillance tests for hepatocellular carcinoma (HCC) are needed. The GALAD score (gender, age, α-fetoprotein [AFP] L3, AFP, and des carboxyprothrombin) has been shown to have excellent sensitivity and specificity for HCC in phase 2 studies. We performed a phase 3 biomarker validation study to compare GALAD with AFP in detecting HCC., Methods: This is a prospective study of patients with cirrhosis enrolled at 7 centers. Surveillance for HCC was performed every 6 months at each site, and HCC diagnosis was confirmed per American Association for the Study of Liver Diseases guidelines. Blood for biomarker research was obtained at each follow-up visit and stored in a biorepository. Measurements of AFP, AFP-L3, and des-γ carboxyprothrombin) were performed in a FujiFilm laboratory by staff blinded to clinical data. The performance of GALAD in detecting HCC was retrospectively evaluated within 12 months before the clinical diagnosis. All analyses were conducted by an unblinded statistician in the EDRN data management and coordinating center., Results: A total of 1,558 patients with cirrhosis were enrolled and followed for a median of 2.2 years. A total of 109 patients developed HCC (76 very early or early stage), with an annual incident rate of 2.4%. The areas under the curve for AFP and GALAD within 12 months before HCC were 0.66 and 0.78 (P < .001), respectively. Using a cutoff for GALAD of -1.36, the specificity was 82%, and the sensitivity at 12 months before HCC diagnosis was 62%. For comparison, performance of AFP at 82% specificity showed 41% sensitivity at 12 months before HCC diagnosis (P = .001)., Conclusions: GALAD score, compared to AFP, improves the detection of HCC within 12 months before the actual diagnosis., (Copyright © 2024 AGA Institute. All rights reserved.)

Bladder cancer (BLCA) mortality is higher in African American (AA) patients compared with European American (EA) patients, but the molecular mechanism underlying race-specific differences are unknown. To address this gap, we conducted comprehensive RNA-Seq, proteomics, and metabolomics analysis of BLCA tumors from AA and EA. Our findings reveal a distinct metabolic phenotype in AA BLCA characterized by elevated mitochondrial oxidative phosphorylation (OXPHOS), particularly through the activation of complex I. The results provide insight into the complex I activation-driven higher OXPHOS activity resulting in glutamine-mediated metabolic rewiring and increased disease progression, which was also confirmed by [U]13C-glutamine tracing. Mechanistic studies further demonstrate that knockdown of NDUFB8, one of the components of complex I in AA BLCA cells, resulted in reduced basal respiration, ATP production, GLS1 expression, and proliferation. Moreover, preclinical studies demonstrate the therapeutic potential of targeting complex I, as evidenced by decreased tumor growth in NDUFB8-depleted AA BLCA tumors. Additionally, genetic and pharmacological inhibition of GLS1 attenuated mitochondrial respiration rates and tumor growth potential in AA BLCA. Taken together, these findings provide insight into BLCA disparity for targeting GLS1-Complex I for future therapy.

Maintaining genetic diversity in cultured shellfish can be challenging due to high variance in individual reproductive success, founder effects, and rapid genetic drift, but is important to retain adaptive potential and avoid inbreeding depression. To support broodstock management and selective breeding in cultured Pacific oysters (Crassostrea (Magallana) gigas), we developed an amplicon panel targeting 592 genomic regions and SNP variants with an average of 50 amplicons per chromosome. Target SNPs were selected based on elevated observed heterozygosity or differentiation in Pacific oyster populations in British Columbia, Canada. The use of the panel for parentage applications was evaluated using multiple generations of oysters from a breeding program on Vancouver Island, Canada (n = 181) and families selected for Ostreid herpesvirus-1 resistance from the Molluscan Broodstock Program in Oregon, USA (n = 136). Population characterization was evaluated using wild, naturalized, farmed, or hatchery oysters sampled throughout the Northern Hemisphere (n = 189). Technical replicates showed high genotype concordance (97.5%; n = 68 replicates). Parentage analysis found suspected pedigree and sample handling errors, demonstrating the panel's value for quality control in breeding programs. Suspected null alleles were identified and found to be largely population dependent, suggesting population-specific variation impacting target amplification. Null alleles were identified using existing data without the need for pedigree information, and once they were removed, assignment rates increased to 93.0 and 86.0% of possible assignments in the two breeding program datasets. A pipeline for analyzing the amplicon sequence data from sequencer output, amplitools, is also provided., Competing Interests: Conflicts of interest B.J.G.S. is affiliated with Sutherland Bioinformatics. The author has no competing financial interests to declare. Some authors affiliated with ThermoFisher Scientific have potential conflicts considering that the AgriSeq Targeted Genotyping by Sequencing solutions and associated Oligo panels that were designed and validated in the study are offered by ThermoFisher Scientific. However, the selection of markers, and data analysis was primarily conducted by other authors. The authors declare that the research was conducted in a scientific manner without any commercial considerations that could be construed as potential conflict of interest and further declare no other conflicts of interest. The other authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

Cardiovascular disease (CVD) and cardiometabolic risk (CMR) are highly prevalent globally. The interplay between CVD/CMR and COVID-19 morbidity and mortality has been intensely studied over the last three years and has yielded some important discoveries and warnings for public health. Despite many advances in cardiovascular medicine, CVD continues to be the global leading cause of death. Much of this disease burden results from high CMR imposed by behaviors centered around poor nutrition related to lifestyle choices and systemic constraints. Increased CVD/CMR contributed to the COVID-19 pandemic's unprecedented wave of disability and death, and the current state of cardiovascular health been equated to a "Population Code Blue." There is an urgent and unmet need to reorient our priorities towards health promotion and disease prevention. This manuscript will review how nutrition and lifestyle affect outcomes in COVID-19 and how some interventions and healthy lifestyle choices can markedly reduce disease burden, morbidity, and mortality., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 The Author(s).)

Colorectal cancer (CRC) is the main driver of fatality and the 3rd most often determined malignancy. Despite advances in detection and therapy, colorectal cancer (CRC) endures as the largest driver of cancer-related morbidity, and mortality. Modern habits and dietary negligence might be one of the reasons that have enhanced cancer prevalence. Thus, changes in Dietary habits will have a better impact, and help in finding a better cure for CRC. Initially, CRC was explored as a genetic event and currently, the research is focused on the epigenetic modifications of chromatin and microRNA (miRNA) in CRC cells. Natural products such as Curcumin, Resveratrol, Flavonoids, and Ellagitannins are been explored as compounds from the perspective of genetic, epigenetic, and miRNA modifications which will have future therapeutic aspects. Also, the extracts of these key players and their analogs will intervene the signaling pathway activation that involves in cancer propagation, apoptosis, cell cycle arrest, and epigenetic and miRNA modifications. Modulations of these miRNAs, and modification globally might have impact on CRC progression, and cancer tumor cell sensitivity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)