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Breast cancer with increased risk in women is identified with Breast Magnetic Resonance Imaging (Breast MRI) and this helps in evaluating treatment therapies. Breast MRI is time time-consuming process that involves the assessment of current imaging. This research work depends on the detection of breast cancer at the earlier stages. Among various cancers, breast cancer in women occurs in larger accounts for almost 30% of estimated cancer cases. In this research, many steps are followed for breast cancer detection like pre-processing, segmentation, augmentation, extraction of features, and cancer detection. Here, the median filter is utilized for pre-processing, as well as segmentation is followed after pre-processing, which is done by Psi-Net. Moreover, the process of augmentation like shearing, translation, and cropping are followed after segmentation. Also, the segmented image tends to process feature extraction, where features like shape features, Completed Local Binary Pattern (CLBP), Pyramid Histogram of Oriented Gradients (PHOG), and statistical features are extracted. Finally, breast cancer is detected using the DL model, SqueezeNet. Here, the newly devised Flamingo Search SailFish Optimizer (FSSFO) is used in training Psi-Net as well as SqueezeNet. Furthermore, FSSFO is the combination of both the Flamingo Search Algorithm (FSA) and SailFish Optimizer (SFO).

Background: Surgery has been the standard procedure for resectable primary LC. Survival after stereotactic body radiation therapy, another treatment, is significantly biased due to preponderance of data from patients deemed unsuitable for surgery. We examined survival of patients refusing surgery in favor of radiation therapy., Methods: We used the Surveillance, Epidemiology, and End Results database to identify patients with primary Stage I NSCLC diagnosed between 2007 and 2016. Patients were excluded if it was unknown if they were recommended for surgery or if surgery was contraindicated. Multiple predictors were assessed: radiation versus surgery, age at diagnosis, sex, race/ethnicity, health insurance status, marital status, tumor size, and histology. A multivariate analysis was performed to estimate hazard ratios and generate Kaplan-Meier survival curves., Results: When adjusted for confounding variables, survival was greater for patients undergoing surgical resection than those refusing surgery in favor of radiation (HR adj 2.66; 95% CI: 2.27-3.11, p < 0.001) or for those receiving no standardized treatment (HR adj 4.43; 95% CI: 3.57-5.50, p < 0.001)., Conclusions: SBRT is an effective treatment for inoperable early LC but there is limited data comparing outcomes against surgical resection. When eligible for both, patients refusing surgery and choosing radiation had worse survival when adjusting for variables including age, tumor size, and histology, and suggests that surgical resection is a superior treatment modality., (© 2024 Wiley Periodicals LLC.)

Introduction: This scoping review investigates the extent and nature of existing evidence on the role of non-governmental organizations (NGOs) and related mechanisms of engagement and challenges in issues of caring for older persons through digital technologies. We map research and practice gaps, contributing factors and best practices in NGOs. The rising use of digital technology in health care and the role that NGOs have in supporting older people in this context is relevant to nurses and service development leaders, particularly in the context of a rapidly changing care in the 21 st century., Methods: A three-stage systematic and comprehensive search strategy based on the JBI methodology for scoping reviews was employed across multiple databases and grey literature sources., Results: In this review, 8,348 abstracts were retrieved. After deduplication, 7,099 titles and abstracts were reviewed. A total of 263 publications were selected for full-text review and 50 included for analysis. NGOs use digital tools to directly engage older adults in programs (e. g., information delivery) and indirectly to collaborate with other organizations (e.g., training programs) to promote digital inclusion. Factors such as individual capabilities, trust and access, technological factors (accessibility and user-friendliness of technology), and socio-cultural and system-wide factors affect how NGOs engage with older adults., Conclusion: Our findings are summarized in the key domains: key organizations, mode of engagement, interorganizational process and digital technology are discussed and offer current insights into the varied engagement of NGOs with older people and its challenges concerning technology. Many interrelated factors, along with barriers and facilitators that influence older persons' engagement with technology, have been identified., (Copyright © 2024. Published by Elsevier GmbH.)

Advances in medicine allow children with previously fatal conditions to survive longer and present as transplant candidates; some requiring multiple solid-organ transplants (MSOT). There is limited data on clinical outcomes and no data on quality of life (QoL). In this mixed methods cohort study clinical outcomes from the NHSBT registry were analysed for all patients who received a kidney and one other solid-organ transplant as a child between 2000 and 2021 in the UK. QoL was measured using the PedsQL 3.0 Transplant Module questionnaire. 92 children met the inclusion criteria: heart/heart-lung and kidney (n = 15), liver and kidney (n = 72), pancreas and kidney (n = 4) and multivisceral (n = 1). Results showed excellent patient and graft survival, comparable to single-organ transplants. Allograft survival and rejection were significantly better in patients with combined liver and kidney transplants compared to patients with sequential liver and kidney transplants. QoL was excellent with a mean score of 74%. Key findings included a significant improvement in QoL post-transplant. This is the first study to look at clinical and QoL outcomes in MSOT recipients. The results indicate excellent long-term outcomes. All children born with conditions leading to end-stage disease in multiple solid-organs should be assessed as transplant candidates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Paessler, Maple, Cortes, Simmonds, Tse, Raja, Muorah, Kessaris and Stojanovic.)

Artificial intelligence (AI) uses sophisticated algorithms to "learn" from large volumes of data. This could be used to optimise recruitment of blood donors through predictive modelling of future blood supply, based on previous donation and transfusion demand. We sought to assess utilisation of predictive modelling and AI blood establishments (BE) and conducted predictive modelling to illustrate its use. A BE survey of data modelling and AI was disseminated to the International Society of Blood transfusion members. Additional anonymzed data were obtained from Italy, Singapore and the United States (US) to build predictive models for each region, using January 2018 through August 2019 data to determine likelihood of donation within a prescribed number of months. Donations were from March 2020 to June 2021. Ninety ISBT members responded to the survey. Predictive modelling was used by 33 (36.7%) respondents and 12 (13.3%) reported AI use. Forty-four (48.9%) indicated their institutions do not utilise predictive modelling nor AI to predict transfusion demand or optimise donor recruitment. In the predictive modelling case study involving three sites, the most important variable for predicting donor return was number of previous donations for Italy and the US, and donation frequency for Singapore. Donation rates declined in each region during COVID-19. Throughout the observation period the predictive model was able to consistently identify those individuals who were most likely to return to donate blood. The majority of BE do not use predictive modelling and AI. The effectiveness of predictive model in determining likelihood of donor return was validated; implementation of this method could prove useful for BE operations., (© 2024 British Blood Transfusion Society.)

Abstract: Cytomegalovirus (CMV) reactivation is a major complication among seropositive allogeneic hematopoietic cell transplantation recipients; however, data on CMV reactivation after chimeric antigen receptor (CAR) T-cell therapy are limited. We report the incidence and outcomes of 95 adult CMV-seropositive patients who received CAR T-cell therapy between February 2018 and February 2023. CMV outcomes were CMV reactivation (any viremia) and clinically significant CMV infection (cs-CMV). Thirty-one patients (33%) had evidence of CMV reactivation (any viremia), and 10 patients (11%) had cs-CMV. The median time from CAR T-cell infusion to CMV reactivation was 19 days (interquartile range [IQR], 9-31). The cumulative incidence of CMV (any viremia) was significantly higher among patients with grade 3 to 4 cytokine release syndrome (67 vs 28%; P = .01), and those who received corticosteroids (39 vs 21%; P = .03), anakinra (56 vs 28%; P = .02), or ≥2 immunosuppressants (41 vs 21%; P = .02). Receipt of corticosteroids (18 vs 0%; P = .004), tocilizumab (14 vs 0%; P = .04), anakinra (33 vs 7%; P = .008), and ≥2 immunosuppressants (20 vs 0%; P = .001) were all associated with cs-CMV. Receiving ≥2 immunosuppressants was associated with a twofold increase in CMV reactivation in multivariate analyses (adjusted odds ratio [aOR], 2.27; 95% confidence interval, 1.1-4.8; P = .03). Overall, the 1-year mortality was significantly higher in those with CMV reactivation (57% vs 23%; P = .001). Immunosuppression, particularly with corticosteroids, for the management of CAR T-cell toxicities, is a major risk factor for CMV reactivation., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

The presentation of the Mesothelioma and Radical Surgery 2 trial, a randomized controlled trial comparing pleurectomy/decortication to no surgery, injected new data into the contentious discussion surrounding the use of surgery in the management of diffuse pleural mesothelioma. We review the trial results in the context of the existing work surrounding the use of surgery in pleural mesothelioma., (Copyright © 2024. Published by Elsevier Inc.)

Immunotherapies have shown great promise in pleural mesothelioma (PM), yet most patients still do not achieve significant clinical response, highlighting the importance of improving understanding of the tumor microenvironment (TME). Here, we utilized high-throughput, single-cell RNA-sequencing to de novo identify 54 expression programs and construct a comprehensive cellular catalogue of the PM TME. We found four cancer-intrinsic programs associated with poor disease outcome and a novel fetal-like, endothelial cell population that likely responds to VEGF signaling and promotes angiogenesis. Throughout cellular compartments, we observe substantial difference in the TME associated with a cancer-intrinsic sarcomatoid signature, including enrichment in fetal-like endothelial cells, CXCL9+ macrophages, cytotoxic, exhausted, and regulatory T cells, which we validated using imaging and bulk deconvolution analyses on independent cohorts. Finally, we show, both computationally and experimentally, that NKG2A-HLA-E interaction between NK and tumor cells represents an important new therapeutic axis in PM, especially for epithelioid cases.

Lymphocyte activation gene 3 (LAG3) is an inhibitory receptor that plays a critical role in controlling T cell tolerance and autoimmunity and is a major immunotherapeutic target. LAG3 is expressed on the cell surface as a homodimer but the functional relevance of this is unknown. In this study, we show that the association between the TCR/CD3 complex and a murine LAG3 mutant that cannot dimerize is perturbed in CD8+ T cells. We also show that LAG3 dimerization is required for optimal inhibitory function in a B16-gp100 tumor model. Finally, we demonstrate that a therapeutic LAG3 Ab, C9B7W, which does not block LAG3 interaction with its cognate ligand MHC class II, disrupts LAG3 dimerization and its association with the TCR/CD3 complex. These studies highlight the functional importance of LAG3 dimerization and offer additional approaches to therapeutically target LAG3., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Monocyte-derived macrophages (mo-macs) drive immunosuppression in the tumor microenvironment (TME) and tumor-enhanced myelopoiesis in the bone marrow (BM) fuels these populations. Here, we performed paired transcriptome and chromatin analysis over the continuum of BM myeloid progenitors, circulating monocytes, and tumor-infiltrating mo-macs in mice and in patients with lung cancer to identify myeloid progenitor programs that fuel pro-tumorigenic mo-macs. Analyzing chromatin accessibility and histone mark changes, we show that lung tumors prime accessibility for Nfe2l2 (NRF2) in BM myeloid progenitors as a cytoprotective response to oxidative stress. NRF2 activity is sustained and increased during monocyte differentiation into mo-macs in the lung TME to regulate oxidative stress, in turn promoting metabolic adaptation, resistance to cell death, and contributing to immunosuppressive phenotype. NRF2 genetic deletion and pharmacological inhibition significantly reduced mo-macs' survival and immunosuppression in the TME, enabling NK and T cell therapeutic antitumor immunity and synergizing with checkpoint blockade strategies. Altogether, our study identifies a targetable epigenetic node of myeloid progenitor dysregulation that sustains immunoregulatory mo-macs in the TME.

Background: This protocol outlines a scoping review with the objective of identifying and exploring planetary health considerations within existing health guidelines and health technology assessments (HTA). The insights gained from this review will serve as a basis for shaping future Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidance on planetary health., Methods: We will adhere to the JBI methodology for scoping reviews. We will conduct a comprehensive search and screening of results in all languages across various databases including MEDLINE, EMBASE, CINAHL, Global Health, Health Systems Evidence, Greenfile, and Environmental Issues. Additionally, we will supplement this search with resources such as the GIN library, BIGG database, Epistemonikos, GRADE guidelines repository, GRADEpro Guideline Development Tool Database, MAGICapp, NICE website, WHO websites, and a manual exploration of unpublished relevant documents using Google incognito mode. Two independent reviewers will screen and assess the full texts of identified documents according to the eligibility criteria. The following information from each full text will be extracted: document title; first author's name; publication year; language; document type; document as a guideline or HTA; the topic/discipline; document purpose/study objective; developing/sponsoring organization; the country in which the study/guideline/HTA report was conducted; definition of planetary health or related concept provided; types of planetary health experts engaged; study methods; suggested methods to assess planetary health; use of secondary data on planetary health outcomes; description for use of life cycle assessment; description for assessing the quality of life cycle; population/intended audience; interventions; category; applicable planetary health boundaries; consideration of social justice/global equity; phase of intervention in life cycle related to planetary health addressed; the measure of planetary health impact; impact on biodiversity/land use; one health/animal welfare mention; funding; and conflict of interest. Data analysis will involve a combination of descriptive statistics and directed content analysis, with results presented in a narrative format and displayed in tables and graphs., Discussion: The final review results will be submitted to open-access peer-reviewed journals for publication when they become available. The research findings will also be disseminated at relevant planetary health conferences and workshops., Systematic Review Registration: Open Science Framework ( https://osf.io/3jmsa )., (© 2024. The Author(s).)

Radiation-based gauges have been widely utilized in the industry as a dependable, non-destructive method of measuring metal layer thickness. It is only possible to trust the conventional radiation thickness meter when the material's composition is known in advance. Thickness measurement errors are to be anticipated in contexts like rolled metal factories, where the real component of the material could diverge greatly from the stated composition. An X-ray-based device was suggested in this study to measure aluminum sheet thickness and identify the type of its alloys. Transmission and backscattered X-ray energy were recorded using two sodium iodide detectors while a 150 kV X-ray tube in the described detection system was operated. Aluminum layers of varying thicknesses (2-45 mm) and alloys (1050, 3105, 5052, and 6061) were simulated to be placed between the X-ray source and the transmission detector. The development of radiation-based systems used the MCNP code as a very powerful framework to imitate the detecting architecture and the spectra acquired by the detectors. The recorded signals were transferred to the frequency domain using the Fourier transform, and the frequency characteristics were extracted from them. Two GMDH neural networks were trained using these characteristics: one to identify the alloy type and another to determine the aluminum layer's thickness. The classifier network had a 92.2% success rate in identifying the alloy type, while the predictive network had a 1.9% error rate in determining the thickness of the aluminum layer. By extracting important characteristics and using powerful neural networks, this study was able to improve the precision with which aluminum layer thickness was measured and correctly identify the alloy type. The suggested method is used to determine the thickness of aluminum and its alloy sheets and may also be applied to other metals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Risks of contralateral kidney abnormalities and chronic kidney disease necessitate follow-up for unilateral multicystic dysplastic kidneys (MCDK). A nationwide survey of senior UK pediatricians was conducted. Of the 60 responses obtained, 62% routinely perform a dimercaptosuccinic acid scan to confirm diagnosis. Eight percent routinely perform a cystogram to investigate contralateral vesicoureteric reflux. Sixty-two percent would routinely measure renal function (frequency ranging from once only to "every 2 years"). Twenty-five percent recalled MCDK nephrectomy being performed within the previous 5 years. Respondents voiced concerns that national guidance may result in an overcautious approach but could balance consensus and safe variation, and offer families choice and reassurance. The mean estimated cost of follow-up from birth to 18 years ranged from £258 to £3854. Results demonstrate significant variation in management, highlighting the need for a clear pathway to decrease unwanted variability and to ensure those at high risk of renal sequelae are recognized early, without undue investigatory burden., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Evidence for necrotising otitis externa (NOE) diagnosis and management is limited, and outcome reporting is heterogeneous. International best practice guidelines were used to develop consensus diagnostic criteria and a core outcome set (COS)., Methods: The study was pre-registered on the Core Outcome Measures in Effectiveness Trials (COMET) database. Systematic literature review identified candidate items. Patient-centred items were identified via a qualitative study. Items and their definitions were refined by multidisciplinary stakeholders in a two-round Delphi exercise and subsequent consensus meeting., Results: The final COS incorporates 36 items within 12 themes: Signs and symptoms; Pain; Advanced Disease Indicators; Complications; Survival; Antibiotic regimes and side effects; Patient comorbidities; Non-antibiotic treatments; Patient compliance; Duration and cessation of treatment; Relapse and readmission; Multidisciplinary team management.Consensus diagnostic criteria include 12 items within 6 themes: Signs and symptoms (oedema, otorrhoea, granulation); Pain (otalgia, nocturnal otalgia); Investigations (microbiology [does not have to be positive], histology [malignancy excluded], positive CT and MRI); Persistent symptoms despite local and/or systemic treatment for at least two weeks; At least one risk factor for impaired immune response; Indicators of advanced disease (not obligatory but mut be reported when present at diagnosis). Stakeholders were unanimous that there is no role for secondary, graded, or optional diagnostic items. The consensus meeting identified themes for future research., Conclusion: The adoption of consensus-defined diagnostic criteria and COS facilitates standardised research reporting and robust data synthesis. Inclusion of patient and professional perspectives ensures best practice stakeholder engagement.

There are fewer studies on Trichoderma diversity in agricultural fields. The rhizosphere of 16 crops was analyzed for Trichoderma species in 7 districts of Rajasthan state of India. Based on DNA sequence of translation elongation factor 1α (tef-1α), and morphological characteristics, 60 isolates were identified as 11 species: Trichoderma brevicompactum, species in Harzianum clade identified as T. afroharzianum, T. inhamatum, T. lentiforme, T. camerunense, T. asperellum, T. asperelloides, T. erinaceum, T. atroviride, T. ghanense, and T. longibrachiatum. T. brevicompactum is the most commonly occurring strain followed by T. afroharzianum. No new species were described in this study. T. lentiforme, showed its first occurrence outside the South American continent. The morphological and cultural characteristics of the major species were observed, described, and illustrated in detail. The isolates were tested for their antagonistic effect against three soilborne plant pathogens fungi: Sclerotium rolfsii, Rhizoctonia solani, and Fusarium verticillioides in plate culture assays. One of the most potent strains was T. afroharzianum BThr29 having a maximum in vitro inhibition of S. rolfsii (76.6%), R. solani (84.8%), and F. verticillioides (85.7%). The potential strain T. afroharzianum BThr29 was also found to be efficient antagonists against soil borne pathogens in in vivo experiment. Such information on crop selectivity, antagonistic properties, and geographic distribution of Trichoderma species will be beneficial for developing efficient Trichoderma-based biocontrol agents., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Dignity is a central value in care for aged adults, and it must be protected and respected. With demographic changes leading to an aging population, health ministries are increasingly investing in digitalization. However, using unfamiliar digital technology can be challenging and thus impact aged adults' dignity and well-being. The INNOVATEDIGNITY project aims to research new, dignified ways of engaging with aged adults to shape digital developments in care delivery. This qualitative study aimed to explore how innovative digitally-led healthcare have influenced aged adults' well-being and dignity through three studies conducted as part of the INNOVATEDIGNITY project: a scoping review, an empirical study and a policy analysis. The three documents were analysed to uncover meanings relevant to the research problem revealing four main themes: the advantages of new technologies in facilitating aged adults' well-being, the rupture of dignity due to bewilderment in the digital world, aged adults' dignity is affected by their worries about human face of care being replaced by technology and preserving aged adults' dignity in digitally-led healthcare. Digitalization in healthcare impacts aged adults' well-being as providing new opportunities for care, but preserving aged adults' dignity when working with unfamiliar digital innovations is challenging. Aged adults need to be informed about the use of technology in their care and supported to develop the necessary digital skills to better adapt to digitally-led healthcare. The circumstances, conditions and needs of individuals should remain central when implementing new technologies in healthcare settings in a dignified way., (© 2024 The Authors. Nursing Philosophy published by John Wiley & Sons Ltd.)

Purpose of Review: There is ample evidence of the benefits and safety of low-density lipoprotein (LDL)-lowering therapies in the prevention of atherosclerotic cardiovascular disease. While statins remain the first-line agent for LDL reduction, several new therapies are now available. This narrative review provides an overview of currently available non-statin LDL-lowering agents, specifically mechanisms of action and data on efficacy and safety. It also discusses recommendations on their use in clinical practice., Recent Findings: Ezetimibe, PCSK9 inhibitors, and bempedoic acid have proven safe and efficacious in reducing cardiovascular events in large randomized controlled trials. Inclisiran is a promising agent that suppresses PCSK9 mRNA translation and is currently under investigation in a large clinical outcomes randomized controlled trial assessing its effect on clinical outcomes. Expert consensus advocates for lower LDL targets in higher risk patients and escalation to or a combination of non-statin therapies as needed to achieve these goals., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Surgical resection is the main treatment for early-stage non-small cell lung cancer (NSCLC), but recurrence remains a concern. Adjuvant chemotherapy has been shown to have survival benefits for resected stage II and III NSCLC, but debate continues regarding its use in stage I NSCLC. High-risk features, such as tumor size and stage, are considered in deciding whether to administer adjuvant chemotherapy., Methods: The data of 666,689 patients diagnosed with lung cancer from 2004 to 2016 were collected from the Surveillance, Epidemiology, and End Results database. Ultimately, 26,160 patients diagnosed with stage I NSCLC were included in the study based on a screening procedure., Results: After matching, 4,285 patients were identified, of whom 1,440 (33.6%) received chemotherapy. High-risk clinicopathologic features, including a high histologic grade, visceral pleural invasion (VPI), the examination of an insufficient number of lymph nodes (LNs), and limited resection, were independent risk factors for a poor prognosis. Chemotherapy significantly improved lung cancer-specific survival (LCSS) and overall survival (OS) in stage I patients with VPI [LCSS: hazard ratio (HR): 0.839, 95% confidence interval (CI): 0.706-0.998, P=0.047; OS: HR: 0.711, 95% CI: 0.612-0.826, P<0.001], regardless of whether or not the patient had fewer than 11 LNs (LCSS: HR: 0.809, 95% CI: 0.664-0.986, P=0.04; OS: HR: 0.677, 95% CI: 0.570-0.803, P<0.001). Chemotherapy was only observed to improve OS for stage IB patients with a high histologic grade when combined with either or both of the following high-risk factors: the presence of VPI and fewer than 11 LNs examined., Conclusions: The presence of VPI was the dominant predictor and the examination of an insufficient number of LNs was the secondary indicator, and a high histologic grade was a potential indicator of the need to administer chemotherapy in the treatment of stage I NSCLC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-305/coif). N.S. obtained research grants from Eli Lilly, Chugai Pharmaceutical, Taiho Pharmaceutical, Pfizer, Ono Pharmaceutical, Nippon Kayaku, Takeda Pharmaceutical, Eisai, Shionogi, Daiichi Sankyo, and Boehringer Ingelheim and received speaking honoraria from Eli Lilly, AstraZeneca, MSD, Chugai Pharmaceutical, Taiho Pharmaceutical, Pfizer, Ono Pharmaceutical, Nippon Kayaku, Takeda Pharmaceutical, Daiichi Sankyo, Boehringer Ingelheim, Novartis, Kyowa Kirin, and Bristol Myers Squibb. The other authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Objectives: Time-to-treatment initiation is an important consideration for patients undergoing thoracic surgery for early-stage lung cancer because delays have the potential to adversely affect outcomes. This study seeks to quantify time-to-treatment initiation for patients with clinical stage I lung cancer, explore patient factors and predictors that lead to an increased time-to-treatment initiation, and compare surgeon perception of appropriate time-to-treatment initiation to the results., Methods: Time-to-treatment initiation was determined for patients enrolled in the Mount Sinai Initiative for Early Lung Cancer Research on Treatment study who underwent surgical resection for clinical stage I lung cancer between March 2016 and December 2021. The following dates were determined: (1) date of first suspicious radiologic imaging, (2) date of first biopsy, and (3) date of surgery. A total of 15 thoracic surgeons who participated in the Mount Sinai Initiative for Early Lung Cancer Research on Treatment were assessed on their perception on time-to-treatment initiation., Results: For 638 patients, median time from first suspicious imaging findings to biopsy was 40 days, biopsy to surgery was 37 days, and suspicious imaging to surgery was 84 days. Significant factors that resulted in longer time-to-treatment initiation in the multivariate analysis were African American or Black race ( P  = .005), vascular disease ( P  = .01), and median household income less than $75,000 ( P  = .04). Although the surgeon's perception was that the average time from biopsy to surgery was 28 days, it was longer for 63.5% of participants; surgeon perception of maximum time between diagnosis and surgery was 84 days and longer for 28.7% of participants., Conclusions: Patient factors such as race, income, and comorbidities were found to have differences in time-to-treatment initiation. Delays to surgery exceeded the expectations of thoracic surgeons., Competing Interests: D.F.Y. is a named inventor on a number of patents and patent applications related to the evaluation of chest diseases including measurements of chest nodules; has received financial compensation for the licensing of these patents; is a consultant and co-owner of Accumetra, a private company developing tools to improve the quality of CT imaging; is on the advisory board and owns equity in HeartLung, a company that develops software related to CT scans of the chest; is on the medical advisory board of Median Technology that is developing technology related to analyzing pulmonary nodules; and is on the medical advisory board of Carestream, a company that develops radiography equipment and has consulted for Genentech, AstraZeneca, and Pfizer. C.I.H. is an inventor of the patents and pending patents owned by Cornell Research Foundation (as of April 2009, she has divested herself of all royalties and other interests arising from these) and is on the medical advisory board for LungLife AI. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2024 The Author(s).)

Background: Recurrent or locally advanced peri-hilar cholangiocarcinoma (PHCC) usually involves the portal vein (PV) leading to significant stenosis. With disease progression, clinical symptoms such as ascites, bleeding, and hepatic insufficiency are usually observed. Little is know about the benefit of PV stenting in relieving the symptoms associated to portal hypertension and allowing anticancer therapies. The aim of this study is to review our experience in PV stenting for PHCC patients., Methods: From 2014 to 2022, data from PHCC patients underwent PV stenting at Verona University Hospital, Italy, were reviewed. The indications were: gastrointestinal bleeding from esophagus-gastric varices, ascites not responsive to medical therapy, severe thrombocytopenia, liver insufficiency (hepatic jaundice, coagulopathy, and/or hyperammoniemia), or asymptomatic high-grade PV stenosis. Cavernous transformation and intrahepatic thrombosis in both sides of the liver were considered contraindication. Systematic anticoagulation therapy was not administered., Results: Technical success was achieved in all 16 (100 %) patients. The improvement of clinical symptoms were observed in 12 (75 %) patients. Anticancer therapy was administrated in 11 (69 %) patients. 2 (13 %) complications were observed: 1 biliary injury and 1 recurrent cholangitis that required a percutaneous trans-hepatic biliary drainage placement. Stent occlusion for tumor progression occurred in 1 patient and a re-stenting procedure was successfully performed. No case of thrombotic stent occlusion was observed during follow up. The 1-year stent patency was 86 % and the median patency period was 8 months (IQR, 4-12)., Conclusion: PV stenting is a feasible and safe palliative treatment that improves clinical condition, allow anticancer therapies, and provide a better quality of life., Competing Interests: Declaration of competing interest All authors state that they have no conflict of interest to disclose., (© 2024 Published by Elsevier Ltd.)

Introduction: We aimed to compare outcomes of patients with first primary clinical T1a-bN0M0 NSCLC treated with surgery or stereotactic body radiation therapy (SBRT)., Methods: We identified patients with first primary clinical T1a-bN0M0 NSCLCs on last pretreatment computed tomography treated by surgery or SBRT in the following two prospective cohorts: International Early Lung Cancer Action Program (I-ELCAP) and Initiative for Early Lung Cancer Research on Treatment (IELCART). Lung cancer-specific survival and all-cause survival after diagnosis were compared using Kaplan-Meier analysis. Propensity score matching was used to balance baseline demographics and comorbidities and analyzed using Cox proportional hazards regression., Results: Of 1115 patients with NSCLC, 1003 had surgery and 112 had SBRT; 525 in I-ELCAP in 1992 to 2021 and 590 in IELCART in 2016 to 2021. Median follow-up was 57.6 months. Ten-year lung cancer-specific survival was not significantly different: 90% (95% confidence interval: 87%-92%) for surgery versus 88% (95% confidence interval: 77%-99%) for SBRT, p = 0.55. Cox regression revealed no significant difference in lung cancer-specific survival for the combined cohorts (p = 0.48) or separately for I-ELCAP (p = 1.00) and IELCART (p = 1.00). Although 10-year all-cause survival was significantly different (75% versus 45%, p < 0.0001), after propensity score matching, all-cause survival using Cox regression was no longer different for the combined cohorts (p = 0.74) or separately for I-ELCAP (p = 1.00) and IELCART (p = 0.62)., Conclusions: This first prospectively collected cohort analysis of long-term survival of small, early NSCLCs revealed that lung cancer-specific survival was high for both treatments and not significantly different (p = 0.48) and that all-cause survival after propensity matching was not significantly different (p = 0.74). This supports SBRT as an alternative treatment option for small, early NSCLCs which is especially important with their increasing frequency owing to low-dose computed tomography screening. Furthermore, treatment decisions are influenced by many different factors and should be personalized on the basis of the unique circumstances of each patient., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

In this retrospective cohort study of singleton pregnancies in people with sickle cell disease (SCD) delivered at two academic centres between 1990 and 2021, we collected demographic and SCD-related data, pregnancy outcomes, and the highest systolic and diastolic blood pressure (SBP and DBP) at seven time periods. We compared the characteristics of subjects with new or worsening proteinuria (NWP) during pregnancy to those without. We then constructed receiver operating characteristic (ROC) curves to determine the blood pressure (BP) that best identifies those with NWP. The SBP or DBP thresholds which maximized sensitivity and specificity were 120 mmHg SBP (sensitivity: 55.2%, specificity: 73.5%) and 70 mmHg DBP (sensitivity: 27.6%, specificity: 67.7%). The existing BP threshold of 140/90 mmHg lacked sensitivity in both genotype groups (HbSS/HbSβ 0 : SBP = 21% sensitive, DBP = 5.3% sensitive; HbSS/HbSβ + : SBP = 10% sensitive, DBP = 0% sensitive). Finally, percent change in SBP, DBP and MAP were all poor tests for identifying NWP. Existing BP thresholds used to diagnose hypertensive disorders of pregnancy (HDP) are not sensitive for pregnant people with SCD. For this population, lowering the BP threshold that defines HDP may improve identification of those who need increased observation, consideration of early delivery and eclampsia prophylaxis., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Resistant hypertension is a condition in which blood pressure remains elevated despite using 3 or more antihypertensive medications. Though contemporary antihypertensive drug therapies have been essential in treating hypertension, in recent years different studies have explored renal denervation (RDN) as an adjunctive or a replacement modality. Here we summarize an open-label, Symplicity HTN 2 trial and 7 randomized, sham-controlled clinical trials: Spyral-HTN OFF MEDS (Spyral Pivotal), Spyral-HTN ON MEDS, RADIANCE-HTN SOLO, RADIANCE-HTN TRIO, RADIANCE II, SYMPLICITY-HTN 1, and SYMPLICITY-HTN 3, which evaluated safety and efficacy of multiple renal denervation systems (RDN) at lowering blood pressure from baseline, and in comparison, to control group. Prior systematic reviews and meta-analyses evinced a modest reduction of ambulatory and office blood; however, these trials and analyses were limited by short-term follow-up. In our updated comprehensive literature review we summarize the short-term, and long-term effects of RDN, based on the latest randomized clinical trials. Our conclusions based on each summary are unanimous with previous literature findings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Few studies have examined the differential impact of stereotactic body radiotherapy (SBRT) and surgery for early-stage non-small cell lung cancer (NSCLC) on quality of life (QoL) during the first post-treatment year., Methods: A prospective cohort of stage IA NSCLC patients undergoing surgery or SBRT at Mount Sinai Health System had QoL measured before treatment, and 2, 6, and 12 months post-treatment using: 12-item Short Form Health Survey version 2 (SF-12 v2 ) [physical component summary (PCS) and mental component summary (MCS)], Functional Assessment of Cancer Therapy-Lung Cancer Subscale (FACT-LCS), and the Patient Health Questionnaire-4 (PHQ-4) measuring depression and anxiety. Locally weighted scatterplot smoothing (LOWESS) was fitted to identify the best interval knot for the change in the QoL trends post-treatment, adjusted piecewise linear mixed effects model was developed to estimate differences in baseline, 2- and 12-month scores, and rates of change., Results: In total, 503 (88.6%) patients received surgery and 65 (11.4%) SBRT. LOWESS plots suggested QoL changed at 2 months post-surgery. Worsening in PCS was observed for both surgery and SBRT within 2 months after treatment but was only significant for surgical patients (-2.11, P<0.001). Two months later, improvements were observed for surgical but not SBRT patients (0.63 vs. -0.30, P<0.001). Surgical patients had significantly better PCS (P<0.001) and FACT-LCS (P<0.001) scores 1-year post-treatment compared to baseline, but not SBRT patients. Both surgical and SBRT patients reported significantly less anxiety 1-year post-treatment compared to baseline (P<0.001 and P=0.03). Decrease in depression from baseline to 1-year post-treatment was only significant for surgical patients (P<0.001)., Conclusions: Post-treatment, surgical patients exhibited improvements in physical health and reductions in lung cancer symptoms following initial deterioration within the first two months; in contrast, SBRT patients showed persistent decline in these areas throughout the year. Nonetheless, improved mental health was noted across both patient categories post-treatment. Targeted interventions and continuous monitoring are recommended during the initial 2 months post-surgery and throughout the year post-SBRT to alleviate physical and mental distress in patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1201/coif). All authors report that this study was supported by generous grants from the Simons Foundation (International, Ltd.). D.F.Y. is a named inventor on a number of patents and patent applications related to the evaluation of chest diseases including measurements of chest nodules. D.F.Y. has received financial compensation for the licensing of these patents. In addition, he is a consultant and co-owner of Accumetra, a private company developing tools to improve the quality of CT imaging. He is on the advisory board and owns equity in HeartLung, a company that develops software related to CT scans of the chest. He is on the medical advisory board of Median Technology that is developing technology related to analyzing pulmonary nodules and is on the medical advisory board of Carestream, a company that develops radiography equipment. C.I.H. is also an inventor of the patents and pending patents owned by Cornell Research Foundation. As of April 2009, she has divested herself of all royalties and other interests arising from these. She is on the medical advisory board for LungLife Al. The authors have no other conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

The organofluorine hexahydropyrimidine derivatives are used in the drug discovery due to its steric nature to hydrogen and its extreme electronegativity. The Ethyl 5-hydroxy-2-thioxo-4-( p -tolyl)-6-(trifluoromethyl)hexahydropyrimidine-5-carboxylate (ETP5C) compound was synthesized and characterized by NMR ( 13 C and 1 H), FT-IR and UV-Vis spectroscopic techniques for experimentally and theoretically and elemental analyses, mass spectra also investigated. The most stable structure of synthesized molecule was studied by PES analysis in gas and liquid medium. The structural parameters such as bond length and bond angle of the title molecule have been obtained by DFT/B3LYP/6-311++G (d,p) set and compared with the structurally related experimental data of the compounds. The π-to-π* transition of the ETP5C molecule is identified using UV-Vis absorption spectral analysis. In addition, the chemical stability and reactivity are investigated using HOMO-LUMO analysis. The minimal HOMO-LUMO energy gap (4.6255 eV) clearly explains that the ETP5C molecule is more reactive for receptors. The nucleophilic and electrophilic regions such as active sites have been shown by MEP, ELF, LOL and Fukui functions. The second order optical effect has been explained by NLO analysis. The docking was performed with antineoplastic proteins that exhibit against the development of tumor cells., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Heart failure is a significant cause of morbidity and mortality worldwide. Despite advancements in guideline-directed medical therapy and improvements in device-based therapies, patients with advanced heart failure have high rates of mortality regardless of ejection fraction. For patients with reduced ejection fraction who meet criteria, cardiac resynchronization therapy or implantable cardiac defibrillators are options available to improve outcomes. However, not all heart failure patients meet those criteria. Cardiac contractility modulation is an innovative therapy that serves to improve functional outcomes and quality of life, while also modifying pathologic gene expression and preventing further remodeling. In this article, we aim to discuss the major clinical trials investigating cardiac contractility modulation as a suitable therapy for patients with advanced heart failure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)