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Objective: Families of critically ill patients may benefit from receiving a written update of patient care each day. Our objective was to develop a system to facilitate care provider creation of written updates and to determine the effect of implementing this process on the care provider experience., Design: The experiences of ICU care providers (nurses, advanced practice providers, and physicians) were measured monthly during a 3-month pre-intervention and a 3-month intervention period. During the intervention period, written updates were sent to families each day and posted in the electronic medical record. Study investigators assisted by editing and distributing the written communication to families., Setting: An urban academic medical center in the United States., Main Outcome Measures: Nurse-Physician Collaboration Scale (NPCS) and Maslach Burnout Inventory (MBI)., Results: Over the 3-month intervention period, care providers created written communication for families of 152 patients (average 5 ICU days per family). NPCS scores among the 65 participating care providers were significantly lower, indicating greater collaboration during the intervention vs. pre-intervention period: 49.9 (95 % CI 46.4-53.6) vs. 55.4 (95 % CI 51.5-59.3), p = 0.002. MBI scores were similar during the intervention vs. pre-intervention periods. A subset of care providers participated in individual interviews. Care providers reported that the process of creating written communication was acceptable and had clear benefits for both families and the medical team., Conclusions: Use of written communication as a supplement to verbal communication improves collaboration among ICU care providers without affecting symptoms of burnout., Implications for Practice: We created a system to facilitate written communication with ICU families that was acceptable to care providers and improved aspects of their experience. In the future, use of written communication can be enhanced with refinements to the process that reduce the time spent creating written updates while highlighting the benefits to families and care providers., 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.)

Objective: Intravenous contrast injection protocol for certain CT studies at our institution was revised in June 2022 in response to the global shortage of iohexol. This included CT head studies performed for neuro-navigation (contrast dose from 90 mL to 70 mL). The quality of these studies was assessed., Methods: Consecutive CT scans before (n = 32) and after (n = 32) contrast dose reduction were reviewed. Demographic data was obtained from the chart. Subjective observations made by two radiologists in consensus included overall study quality (Likert scale of 1 to 5) and lesion location, margins and internal characteristics that were compared with MRI findings (reference standard) using Fisher's exact test. Superior sagittal sinus attenuation, used as an objective measurement of enhancement, and lesion size were compared using Student's t-test. The institutional database was searched for any study requiring repetition or deemed non-diagnostic., Results/discussion: The average age (61.1 ± 12.7 years and 61.6 ± 14.9 years) and body surface area (BSA) (1.9 ± 0.3 m 2 and 1.9 ± 0.02 m 2 ) was not significantly different (p > 0.05) between groups. There was no significant difference (p > 0.05) in objective or subjective enhancement between the two groups. There was no significant difference between CT and MRI for lesion size, location, number, margins and internal enhancement characteristics in the two groups. No study required repetition or was reported as non-diagnostic. There was no adverse comment about study quality in operative notes., Conclusion: Reduced contrast dose neuro-navigation CT head studies are not different in quality compared to the conventional studies., (Copyright © 2024. Published by Elsevier Inc.)

The Cancer Drug Development Forum (CDDF)'s 'Histology independent drug development - is this the future for cancer drugs?' workshop was set up to explore the current landscape of histology independent drug development, review the current regulatory landscape and propose recommendations for improving the conduct of future trials. The first session considered lessons learnt from previous trials, including innovative solutions for reimbursement. The session explored why overall survival represents the most valuable endpoint, and the importance of duration of response, which can be captured with swimmer and spider plots. The second session on biomarker development and treatment optimisation considered current regulations for companion diagnostics, FDA guidance on histology independent drug development in oncology, and the need to establish cut-offs for the biomarker of tumour mutational burden to identify the patients most likely to benefit from PDL1 treatment. The third session reviewed novel trial designs, including basket, umbrella and platform trials, and statistical approaches of hierarchical modelling where homogeneity between study cohorts enables information to be borrowed between cohorts. The discussion highlighted the need to agree 'common assessment standards' to facilitate pooling of data across studies. In the fourth session, the sharing of data sets was recognised as a key step for improving equity of access to precision medicines across Europe. The session considered how the European Health Data Space (EHDS) could streamline access to medical records, emphasizing the importance of introducing greater accountability into the digital space. In conclusion the workshop proposed 11 recommendations to facilitate histology agnostic drug development., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

There is an urgent need to combat pathogen infestations in crop plants to ensure food security worldwide. To counter this, plants have developed innate immunity mediated by Pattern Recognition Receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and damage- associated molecular patterns (DAMPs). PRRs activate Pattern-Triggered Immunity (PTI), a defence mechanism involving intricate cell-surface and intracellular receptors. The diverse ligand-binding ectodomains of PRRs, including leucine-rich repeats (LRRs) and lectin domains, facilitate the recognition of MAMPs and DAMPs. Pathogen resistance is mediated by a variety of PTI responses, including membrane depolarization, ROS production, and the induction of defence genes. An integral part of intracellular immunity is the Nucleotide-binding Oligomerization Domain, Leucine-rich Repeat proteins (NLRs) which recognize and respond to effectors in a potent manner. Enhanced understanding of PRRs, their ligands, and downstream signalling pathways has contributed to the identification of potential targets for genetically modified plants. By transferring PRRs across plant species, it is possible to create broad-spectrum resistance, potentially offering innovative solutions for plant protection and global food security. The purpose of this chapter is to provide an update on PRRs involved in disease resistance, clarify the mechanisms by which PRRs recognize ligands to form active receptor complexes and present various applications of PRRs and PTI in disease resistance management for plants., (Copyright © 2024. Published by Elsevier Inc.)

The growing population, climate change, and limited agricultural resources put enormous pressure on agricultural systems. A plateau in crop yields is occurring and extreme weather events and urbanization threaten the livelihood of farmers. It is imperative that immediate attention is paid to addressing the increasing food demand, ensuring resilience against emerging threats, and meeting the demand for more nutritious, safer food. Under uncertain conditions, it is essential to expand genetic diversity and discover novel crop varieties or variations to develop higher and more stable yields. Genomics plays a significant role in developing abundant and nutrient-dense food crops. An alternative to traditional breeding approach, translational genomics is able to improve breeding programs in a more efficient and precise manner by translating genomic concepts into practical tools. Crop breeding based on genomics offers potential solutions to overcome the limitations of conventional breeding methods, including improved crop varieties that provide more nutritional value and are protected from biotic and abiotic stresses. Genetic markers, such as SNPs and ESTs, contribute to the discovery of QTLs controlling agronomic traits and stress tolerance. In order to meet the growing demand for food, there is a need to incorporate QTLs into breeding programs using marker-assisted selection/breeding and transgenic technologies. This chapter primarily focuses on the recent advances that are made in translational genomics for crop improvement and various omics techniques including transcriptomics, metagenomics, pangenomics, single cell omics etc. Numerous genome editing techniques including CRISPR Cas technology and their applications in crop improvement had been discussed., (Copyright © 2024. Published by Elsevier Inc.)

Background: RASopathies account for nearly 20% of cases of childhood hypertrophic cardiomyopathy (HCM). Sudden cardiac death (SCD) occurs in patients with RASopathy-associated HCM, but the risk factors for SCD have not been systematically evaluated., Aim: To validate the HCM Risk-Kids SCD risk prediction model in children with RASopathy-associated HCM and investigate potential specific SCD predictors in this population., Methods: Validation of HCM Risk-Kids was performed in a retrospective cohort of 169 patients with a RASopathy-associated HCM from 15 international paediatric cardiology centres. Multiple imputation by chained equations was used for missing values related to the HCM Risk-Kids parameters., Results: Eleven patients (6.5%) experienced a SCD or equivalent event at a median age of 12.5 months (IQR 7.7-28.64). The calculated SCD/equivalent event incidence was 0.78 (95% CI 0.43-1.41) per 100 patient years. Six patients (54.54%) with an event were in the low-risk category according to the HCM Risk-Kids model. Harrell's C index was 0.60, with a sensitivity of 9.09%, specificity of 63.92%, positive predictive value of 1.72%, and negative predictive value of 91%; with a poor distinction between the different risk groups. Unexplained syncope (HR 42.17, 95% CI 10.49-169.56, p < 0.001) and non-sustained ventricular tachycardia (HR 5.48, 95% CI 1.58-19.03, p < 0.007) were predictors of SCD on univariate analysis., Conclusion: Unexplained syncope and the presence of NSVT emerge as predictors for SCD in children with RASopathy-associated HCM. The HCM Risk-Kids model may not be appropriate to use in this population, but larger multicentre collaborative studies are required to investigate this further., Competing Interests: Declaration of Competing Interest Wolf CM: consultancy with Day One Biopharmaceuticals, Inc., BioMarin Pharmaceuticals, Adrenomed AG, and Pliant Therapeutics; ownership interest: Preventage Therapeutics. Zenker M: consultancy with Day One Biopharmaceuticals, Inc. and Novo Nordisk., (Copyright © 2023. Published by Elsevier B.V.)

Thermosynechococcus elongatus-BP1 belongs to the class of photoautotrophic cyanobacterial organisms. The presence of chlorophyll a, carotenoids, and phycocyanobilin are the characteristics that categorize T. elongatus as a photosynthetic organism. Here, we report the structural and spectroscopic characteristics of a novel hemoglobin (Hb) Synel Hb from T.elongatus, synonymous with Thermosynechococcus vestitus BP-1. The X-ray crystal structure (2.15 Å) of Synel Hb suggests the presence of a globin domain with a pre-A helix similar to the sensor domain (S) family of Hbs. The rich hydrophobic core accommodates heme in a penta-coordinated state and readily binds an extraneous ligand (imidazole). The absorption and circular dichroic spectral analysis of Synel Hb reiterated that the heme is in Fe III+ state with a predominantly α-helical structure similar to myoglobin. Synel Hb displays higher resistance to structural perturbations induced via external stresses like pH and guanidium hydrochloride, which is comparable to Synechocystis Hb. However, Synel Hb exhibited lower thermal stability compared to mesophilic hemoglobins. Overall, the data is suggestive of the structural sturdiness of Synel Hb, which probably corroborates its origin in extreme thermophilic conditions. The stable globin provides scope for further investigation and may lead to new insights with possibilities for engineering stability in hemoglobin-based oxygen carriers., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

With the rapid population growth, the world is witnessing an ever-increasing demand for energy and natural resources. Consequently, soil, air, and water are polluted with diverse pollutants, including heavy metals (HM). The detection of heavy metals is necessary to remediate them, which is achieved with biosensors. Initially, these HM were detected using atomic absorption spectroscopy (AAS), emission spectroscopy, mass spectrometry, gas chromatography etc., but these were costly and time consuming which further paved a way for microbe-based biosensors. The development of genetic circuits for microbe-based biosensors has become more popular in recent years for heavy metal detection. In this review, we have especially discussed the various types of genetic circuits such as toggle switches, logic gates, and amplification modules used in these biosensors as they are used to enhance sensitivity and specificity. Genetic circuits also allow for rapid and multiple analyte detection at the same time. The use of microbial biosensors for the detection of HM in the soil as well as the water is also described below. Although with a higher success rate than classical biosensors, these microbial biosensors still have some drawbacks like bioavailability and size of the analyte which are needed to be addressed., 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.)

In 2021 an estimated 74 million individuals had diabetes in India, almost all type 2 diabetes. More than half of patients with diabetes are estimated to be undiagnosed and more 90% have dyslipidemia that is associated with accelerated development of atherosclerotic cardiovascular disease (ASCVD). Patients of Indian descent with diabetes have multiple features that distinguish them from patients with diabetes in Western populations. These include characteristics such as earlier age of onset, higher frequency of features of the metabolic syndrome, more prevalent risk factors for ASCVD, and more aggressive course of ASCVD complications. In light of the unique features of diabetes and diabetic dyslipidemia in individuals of Indian descent, the Lipid Association of India developed this expert consensus statement to provide guidance for management of diabetic dyslipidemia in this very high risk population. The recommendations contained herein are the outgrowth of a series of 165 webinars conducted by the Lipid Association of India across the country from May 2020 to July 2021, involving 155 experts in endocrinology and cardiology and an additional 2880 physicians., Competing Interests: Conflict of interest Raman Puri: Boehringer Ingelheim, Novartis Vimal Mehta: Institutional research grants from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, LIB Therapeutics, Novo Nordisk, Torrent P Barton Duell: Advisory activities: Akcea/Ionis, Esperion, Novo Nordisk, Regeneron, Kaneka. Institutional grants: Regeneron, Regenxbio, Retrophin/Travere V Mohan: Research or educational grants from Abbott, AstraZeneca, Boehringer Ingelheim, Dr. Reddy's Lab, Johnson and Johnson, Lifescan, MSD, Novartis, Novo Nordisk, Roche Diabetes Care India Private Ltd, Sanofi-Aventis, USV, other Indian pharmaceutical companies S. S. Iyengar: Dr. Reddy's Lab, Amgen, Emcure, Glenmark, Boehringer Ingelheim, Pfizer, Novartis Vinod Mittal: Boehringer Ingelheim, USV, Cipla, Intas, Emcure, MacLeods S N Narasingan: USV, Novo Nordisk, Eris, Glenmark, Torrent, Boehringer Ingelheim J.B. Chemicals and Pharmaceuticals Nathan D. Wong: Amgen, Amarin, Novartis, Esperion SK Wangnoo: Sanofi- Aventis, Nova Nordisk, Boehringer Ingelheim, Astra Zeneca The other authors report no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Background: Neoadjuvant chemotherapy (NACT) with human epidermal growth factor receptor 2 (HER2) blockade is the preferred approach for treating early and locally advanced HER2-positive breast cancer. There is a lack of robust data comparing pathological complete response (pCR) and survival outcomes in anthracycline-free and anthracycline-containing regimens with single HER2-targeted therapy., Objectives: The present study retrospectively evaluated pCR between two groups: Single HER2-targeted therapy with and without anthracycline., Methods: A total of 215 HER2-positive female breast cancer patients were analyzed who received eitheranthracycline-containing EC-TH (epirubicin and cyclophosphamide, followed by docetaxel and trastuzumab)oranthracycline-free TCH [docetaxel, carboplatin and trastuzumab]. Univariate and multivariate analyses identified prognostic factors for survival and pCR.Kaplan Meier survival curvesdetermined disease-free survival(DFS) and overall survival (OS)., Results: Baseline characteristics were comparable in both treatment groups. The pCR rate was 30.8% in the anthracycline-containing EC-TH group and 40.9% in the anthracycline-free TCH group; p = 0.140. Disease-free survival at 3 years (65.8% vs. 58.4%) and 5 years (49.2% vs. 55.2%) was similar between EC-TH and TCH groups, respectively (log-rank p = 0.550). Three-year (95.5% vs. 92.5%) and five-year (84.4% vs. 80.8%) OSwere also comparable between both groups (log-rank p = 0.485). The anthracycline-containing EC-TH group had a higher incidence of febrile neutropenia (6.4%. vs. 3.6%) and cardiac adverse events (7.7% vs. 4.4%) than the anthracycline-free TCH group., Conclusion: Neoadjuvant anthracycline-free chemotherapy has similar pCR and survival outcomeswith favourable cardiac and non-cardiac adverse effect profiles compared with anthracycline-containing chemotherapy., Competing Interests: Declaration of Competing Interest The authors declare that they do not have any conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Background: One fifth of patients with epithelial ovarian cancers (EOC) present at an early stage (FIGO stage I & II). However, there is scarcity of literature on the outcomes and its predictors. The aim of the study was to assess relapse free survival (RFS), overall survival (OS) and its predictors in early stage EOC., Patients and Methods: In this retrospectively study, we included all patients with early-stage EOC diagnosed between January 2010 and December 2018. Patients with synchronous malignancies were excluded. Clinical profile, clinico-pathological characteristics and treatment details were recorded. Patient underwent initial surgery followed by adjuvant chemotherapy in high-risk disease. Patients with stage IC, or stage II or clear cell histology or high-grade histology irrespective of stage/histological subtype were defined as high-risk disease. Fertility sparing surgery (FSS) [unilateral salpingo-oopherectomy with complete surgical staging] was performed in patient willing to preserve fertility. Primary objective was to assess RFS and OS in all patients with early stage EOC. Secondary objectives were to assess RFS and OS in early stage EOC with high-risk disease, predictors of RFS and OS, and outcomes of FSS. Survival probabilities were estimated according to Kaplan-Meier and compared by the log rank test. Cox's regression model was used to analyze the significance of various factors affecting relapse free survival (RFS) and overall survival (OS)., Results: 195 patients with early stage EOC were recruited with median age of 47 years (range, 16-80 years). FIGO stage I and stage II were seen in 72 % and 18 % patients respectively. Serous subtype was reported in 58 % and high-grade histology in 66 %. 184 patients (94.0%) underwent optimal staging surgery, including 27 (14%) with fertility sparing surgery (FSS). 133 (91.7 %) of 145 patients with high-risk disease received adjuvant chemotherapy (paclitaxel and carboplatin), while 12 (8.3 %) patients opted to remain on observation. At median follow up of 56 months (95 % CI, 46-64 months), 49 (25 %) patients relapsed [including 3 of 27 (11.1 %) who underwent FSS], 18 patients died of progressive disease, while 31 patients were alive and disease free. Estimated OS at 5 years is 87.6 % (95 % CI 79.9-92.5) and RFS is 73.2 % (95 % CI 64.7-80.0). On multivariate analysis tumor grade was predictive of RFS (HR 2.9, p < 0.04) and OS (HR 9.4, p < 0.02)., Conclusions: This study confirms the excellent outcome for patients with early stage EOC. Histological grade of tumor is a significant predictor of OS and RFS. FSS is feasible in selected patients with early EOC., 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., (© 2022 The Authors.)

Study Objective: To describe the diagnostic and surgical challenges in the management of second trimester placenta percreta., Design: Stepwise demonstration of the surgical technique with the use of an educational video., Setting: Second trimester placenta percreta is a rare entity, with very few case reports in the literature. Our video demonstrates the challenges of a minimally invasive approach toward definitive surgical management with hysterectomy. A 39-year-old G7P3 (3 previous cesarean deliveries) female at 17 weeks and 2 days gestation presented with acute abdominal pain to a community hospital. This was a spontaneously conceived pregnancy. Her hemoglobin level on admission was 92 g/L. An ultrasound showed a normal uterus, and the appendix was not visualized. One unit of packed red blood cells was transfused, and she underwent exploratory laparoscopy for a possible retrocecal hematoma/mass seen on computerized tomography. In the operating room, acute hemoperitoneum was visualized with placenta-like tissue invading through the anterior lower uterine segment (Figures 2 & 3). A hemostatic agent (Floseal, Baxter) was placed over the bleeding, and she was then transferred to a tertiary academic center for further management., Interventions: Magnetic resonance imaging was performed on the following day after transfer to our facility, which confirmed placenta percreta at the level of the bladder (Figure 1). Following counseling with a multidisciplinary team and given that there was ongoing bleeding from the invading placental tissue, pregnancy continuation and uterine conservation were not possible. The patient was offered preprocedure termination of pregnancy with intra-cardiac injection of potassium chloride and 350 cc of amniotic fluid was drained at that time. This was done to facilitate visualization for a minimally invasive approach. We describe 5 main challenges of minimally invasive hysterectomy for placental percreta and provide a stepwise approach to mitigating them: visibility, vascular control, bladder dissection, colpotomy, and specimen retrieval. We adapted the previously described laparotomy techniques of progressive uterine devascularization and approach to bladder dissection and colpotomy to laparoscopy [1,2]. In addition, we performed dilatation and evacuation to allow for vaginal specimen removal. The patient's postoperative course was uncomplicated, and she was discharged home in a stable condition., Conclusion: Midtrimester placenta percreta poses significant challenges in diagnosis and surgical management. Total laparoscopic hysterectomy for this condition poses unique challenges but is feasible and safe., (Copyright © 2022 AAGL. Published by Elsevier Inc. All rights reserved.)

Importance: Carboplatin increases the pathological complete remission (pCR) rate in triple negative breast cancer (TNBC) when added to neoadjuvant chemotherapy, however, evidence on its effect on survival outcomes is controversial., Methods: The study was prospectively registered at PROSPERO (CRD42021228386). We systematically searched PubMed, Embase, Cochrane Central Register of Clinical Trials, and conference proceedings from January 1, 2004 to January 30, 2022 for relevant randomized clinical trials (RCTs) of (neo)adjuvant chemotherapy in TNBC patients, with carboplatin in the intervention arm and standard anthracycline taxane (AT) in the control arm. PRISMA guidelines were used for this review. Data were pooled using fixed and random effects models as appropriate on extracted hazard ratios (HR). Individual patient data (IPD)for disease free survival (DFS) and overall survival (OS) were extracted from published survival curves of included RCTs; DFS and OS curves for each trial and the combined population were reconstructed, and HR estimated. The primary outcome was DFS; OS, pCR, and toxicity were secondary outcomes., Results: Eight trials with 2425 patients were included. Carboplatin improved DFS (HR 0.60; 95% CI 0.47 to 0.78; I 2 45%, p < 0.001) compared with AT at trial level and IPD level (HR 0.66; 95%CI, 0.55 to 0.80, p < 0.001) analysis. The OS also improved with carboplatin at both trial level (HR 0.69, 95%CI 0.50 to 0.95, I 2 41%, p = 0.02) and IPD level (HR 0.68; 95%CI, 0.54 to 0.87, p = 0.002) analysis. The pCR as expected, was better in the carboplatin arm (OR 2.11; 95% CI = 1.44-3.08; I 2 67%, p = 0.009). Anaemia and thrombocytopaenia were higher in the carboplatin arm., Conclusion: and relevance: Carboplatin added to (neo)adjuvant chemotherapy in TNBC improves survival, as shown in both trial level and IPD analysis., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Phthalates are known endocrine-disrupting chemicals used indiscriminately as constituents in consumer products including food processing, and packaging, cosmetics, personal care and household items. Although, few studies have assessed the risk of breast cancer on exposure to phthalates, their association with breast cancer risk in Indian women have not yet been evaluated., Methods: We conducted a case-control study involving 171 participants. Urinary concentrations of six phthalate dieters; DMP (Dimethyl phthalate), DEP (Diethyl phthalate), DBP (Dibutyl phthalate), BBP (benzyl butyl phthalate), DEHP (Di-2-ethyl-hexyl phthalate), DINOP (Di-n-octyl phthalate) were estimated by GC-MS and geometric means were calculated. Univariate and multivariable logistic regression was performed to assess breast cancer risk on exposure to phthalates. Genes responsive to phthalates were identified through literature search and matched with NGS data, and gene-enrichment analysis was performed., Results: Significant associations were observed between urinary phthalate concentrations and increased risk of breast cancer for di-butyl phthalate (OR=1.5, 95% CI; 1.06, 2.11, p = 0.002) and di-2-ethyl-hexyl phthalate (>median vs ≤ median; OR=2.97, 95% CI; 1.18, 7.47, p = 0.005) in multivariable analyses. We also found several phthalate-responsive gene mutations in paired breast tumor tissues, which include PTPRD (76.19%), AR (42.86%), CYP1A1 (42.86%), CYP19A1 (23.81%), AHRR (19.05%), PIK3CA (19.05%), CYP1B1 (9.52%), RB1 (9.52%) and MMP9 (9.52%). Gene-enrichment analysis revealed that these genes form a major part of ER/PR, PPAR and HIF-1α-TGF-β signaling cascades involved in breast cancer CONCLUSION: Although the sample size is small, in this first case-control study from India, DBP and DEHP were found to be associated with increased risk of invasive breast cancer and tumor tissues revealed mutations in several phthalate-responsive genes. It is, therefore suggested that human biomonitoring in India and larger studies evaluating the early life genetic and epigenetic alterations on phthalates exposure are required to establish their role in breast carcinogenesis., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Frailty impacts outcomes for patients with lung cancer, but no brief tools have been assessed in patients with metastatic disease. We evaluated the impact of the Modified Frailty Index (mFI) on clinical outcomes for patients with metastatic non-small cell lung cancer (NSCLC)., Methods: We conducted a retrospective cohort study of all patients with Stage IV NSCLC diagnosed in Manitoba between 2011 and 2016 who then received first-line cytotoxic chemotherapy. We assigned mFI scores based on documented comorbidities and collected data on toxicity, progression, and survival. Descriptive statistics characterized the cohort and toxicity experienced. Kaplan-Meier methods were used to evaluate progression-free survival (PFS) and overall survival (OS), followed by multivariable Cox proportional hazards models., Results: Our cohort of 426 (mFI 0/1-2/3+ = 175/196/55) patients, showed no significant association between higher mFI score and incidence of overall chemotherapy toxicity. Patients with mFI 0 experienced more frequent thromboses (p=0.022) and a trend towards less nausea or vomiting (p = 0.059). There was no significant difference in PFS or OS among frailty groups. Poorer performance status, number of metastatic sites, and the absence of a driver mutation were independently associated with poorer PFS and OS. Male sex and not completing chemotherapy were also associated with worse OS., Conclusion: This study is the first to investigate the use of the mFI as a frailty tool in patients with metastatic NSCLC receiving cytotoxic chemotherapy. The mFI does not appear to be strongly associated with treatment-related toxicities, PFS, or OS in patients with metastatic NSCLC receiving first-line cytotoxic chemotherapy., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Radiotherapy of thoracic neoplasms and accidental radiation exposure often results in pneumonitis and fibrosis of lungs. Here, we investigated the potential of amifostine analogs: DRDE-07, DRDE-30, and DRDE-35, in alleviating radiation-induced lung damage., Methods: C57BL/6 mice were exposed to 13.5 Gy thoracic irradiation, 30 min after intraperitoneal administration of the analogs, and assessed for modulation of the pathological response at 12 and 24 weeks., Key Findings: DRDE-07, DRDE-30 and DRDE-35 increased the survival of irradiated mice from 20% to 30%, 80% and 70% respectively. Reduced parenchymal opacity (X-ray CT) in the lungs of DRDE-30 pre-treated mice corroborated well with the significant decrease in Ashcroft score (p < 0.01). Two-fold increase in SOD and catalase activities (p < 0.05), coupled with a 50% increase in GSH content and a 60% decrease in MDA content (p < 0.05) suggested restoration of the antioxidant defence system. A 20% to 40% decrease in radiation-induced apoptotic and mitotic death in the lung tissue (micronuclei: p < 0.01), resulted in attenuated lung and vascular permeability (FITC-Dextran leakage) by 50% (p < 0.01), and a commensurate reduction (~50%) in leukocyte infiltration in the injured tissue (p < 0.05). DRDE-30 abrogated the activation of pro-inflammatory NF-κB and p38/MAPK signaling cascades, suppressing the release of pro-inflammatory cytokines (IL-1β: p < 0.05; TNF-α: p < 0.05; IL-6: p < 0.05) and up-regulation of CAMs on the endothelial cell surface. Reduction in hydroxyproline content (p < 0.01) and collagen suggested inhibition of lung fibrosis which was associated with attenuation of TGF-β/Smad pathway-mediated-EMT., Conclusion: DRDE-30 could be a potential prophylactic agent against radiation-induced lung injury., (Copyright © 2022 Elsevier Inc. All rights reserved.)

It has been suggested that aging and inflammation play key roles in the development of delirium. In the present study, we investigated the differences of the DNAm patterns in the TNF gene between patients with delirium and without. The data and samples derived from previous and ongoing cohort studies were analyzed. DNAm levels of the TNF gene were analyzed using the Illumina EPIC array genome-wide method and pyrosequencing method. Correlations between age and DNAm levels of each CpG were calculated. Several CpG in the TNF gene in blood showed negative correlation between their DNAm and age in delirium cases both with the EPIC array and by the pyrosequencing method. However, there was no CpG that had significant correlation between their DNAm and age regardless of delirium status among buccal samples. On the other hand, among peripheral blood mononuclear cells samples, it was found that several CpG showed negative correlation between their DNAm and age in delirium cases. The evidence of DNAm change in the TNF gene among delirious subjects was demonstrated., (Copyright © 2021 Elsevier Inc. All rights reserved.)