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Yuanyuan Fan,1,* Nazeer Hussain Khan,1,* Muhammad Farhan Ali Khan,2 MD Faysal Ahammad,3 Tayyaba Zulfiqar,2 Razia Virk,4 Enshe Jiang5 1School of Life Sciences, Henan University, Kaifeng, Henan, 475004, People’s Republic of China; 2Department of Pharmacy, Quaid I Azam University, Islamabad, Pakistan; 3Key Laboratory of Natural Medicine and Immune Engineering, School of Medicine, Henan University, Kaifeng, People’s Republic of China; 4Department of Bio-Sciences, University Wah, Rawalpindi, Pakistan; 5Institute of Nursing and Health, Henan University, Kaifeng, 475004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Enshe Jiang, Email esjiang@gmail.comAbstract: Breast cancer (BC) is the most common malignancy affecting women, and its incidence in younger women is rising worldwide. Early-onset of BC is a multi-step process involving various biological aggressive tumors such as triple negative and human epidermal growth factor 2 (HER2)-positive cancers. BC prevention is still arduous across the globe. A series of observational studies have established a conclusive non-genetic clinical link between hypertension (HTN) and the development of invasive BC. Those clinical associations have driven a pharmacological seek to use the anti-hypertension (AHTN) drugs as an effective adjunctive in BC therapy. The use of AHTN, especially beta-blockers and thiazides, has been recognized as a potent anti-tumor drug to mitigate BC progression, reduce the side effects of cancer treatment, and stop the reoccurrence of cancer in the survivors. Considering the dire need to disseminate the research on how AHTN drugs can be opted as the effective adjunctive therapy to cure the BC, the current review aimed to provide an update on novel understandings on association and mechanisms of AHTN-drugs against BC as an additional cancer therapy.Keywords: breast cancer, beta blockers, hypertension, hypertensive drugs, thiazides

Byline: Divya. Jain, Suman. Arora, R. Virk, Medha. Gupta, Kanika. Arora Sir, Coblation (plasma ablation) procedures are performed for various infraglottic conditions like subglottic stenosis, laryngeal papillomatosis (LP) to name [...]

Endoscopic endonasal Trans-sphenoidal surgery for sellar-suprasellar tumors is considered the preferred route. The ideal instruments in skull base surgery should be able to manipulate adequately through the narrow corridors with effective tissue removal and bleeding control and reduce collateral damage to nearby vital structures. The present study sought to compare the nasal morbidity following transnasal sphenoidal surgery for pituitary macroadenoma using Coblation and Electrocautery. 160 undergoing Endoscopic TSS for non-functioning PAs were enrolled. The patients were randomly allocated into Coblation ( n  = 80) and electrocautery ( n  = 80) groups. All operations were performed by the same group of surgeons skilled in their surgical techniques. There were 59 and 53 patients with Knosp grade II tumors in the cautery and coblation group, respectively, while 21 and 27 patients had Knosp grade III tumors. The average duration of surgery using cautery was 96+/-4.5 min, while with coblation, the average time was 83+/-3.5 min, and the difference was statistically significant. Nasal crusting and granulation severity were observed more in the electrocautery group. The coblation group patients had clear surgical fields with few ooze points; the difference between the two groups was significant. Nasal synechiae and decreased nasal patency were common in the electrocautery group. There were no statistical differences in nasal bleeding, nasal deformity, or sense of smell parameters. Advanced medical tools like coblation are safe and effective for the dissection and ablation of the mucosa. They result in better intra-operative visualization and lesser postoperative nasal morbidity, which will help patients achieve a better quality of life., Competing Interests: Conflict of InterestThe authors declare no conflict of interest., (© Association of Otolaryngologists of India 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Polyester-based advanced thin films have versatile industrial applications, especially in the fields of textiles, packaging, and electronics. Recent advances in polymer science and engineering have resulted in the development of advanced amorphous and semi-crystalline polyesters with exceptional performance compared to those of conventional polymeric films. Among these, 1,4-cyclohexanedimethanol (CHDM) and cyclic-monomer-based polyesters have gained considerable attention for their exceptional characteristics and potential applications in smart films. This review article provides a comprehensive overview of the recent advances in the synthesis, characterization, and applications of CHDM and cyclic-monomer-based advanced polymers for smart film applications. It discusses the structure-property relationships of these innovative polyesters and highlights their unique characteristics, including thermal, mechanical, and barrier characteristics. Furthermore, this article also emphasizes the solution, melt, and solid-state polymerizations of the polymers. Special emphasis is placed on the influence of the addition of a second diol or second diacid on the performance characteristics of synthesized polyesters/copolyesters to explore their versatile industrial applications. Additionally, the impact of the stereochemistry of the monomers is explored to optimize the characterization of polyesters suitable for industrial applications. Furthermore, this article explores the potential of these advanced polyesters to be considered as materials for smart film applications, especially in the field of flexible electronics. Finally, this article examines the challenges and future recommendations for the development of CHDM and cyclic-monomer-based polyesters for smart film applications. It discusses potential avenues for further research, including in-depth studies for the synthesis and characterization of polyesters, the development of sustainable and biodegradable alternatives to cyclic monomers, alternative green approaches for the synthesis of polymers, etc. This review article provides valuable insight for researchers in academia and industry who are working in the fields of polymer science and materials engineering.

Introduction: The integration of whole slide imaging (WSI) and artificial intelligence (AI) with digital cytology has been growing gradually. Therefore, there is a need to evaluate the current state of digital cytology. This study aimed to determine the current landscape of digital cytology via a survey conducted as part of the American Society of Cytopathology (ASC) Digital Cytology White Paper Task Force., Materials and Methods: A survey with 43 questions pertaining to the current practices and experiences of WSI and AI in both surgical pathology and cytology was created. The survey was sent to members of the ASC, the International Academy of Cytology (IAC), and the Papanicolaou Society of Cytopathology (PSC). Responses were recorded and analyzed., Results: In total, 327 individuals participated in the survey, spanning a diverse array of practice settings, roles, and experiences around the globe. The majority of responses indicated there was routine scanning of surgical pathology slides (n = 134; 61%) with fewer respondents scanning cytology slides (n = 150; 46%). The primary challenge for surgical WSI is the need for faster scanning and cost minimization, whereas image quality is the top issue for cytology WSI. AI tools are not widely utilized, with only 16% of participants using AI for surgical pathology samples and 13% for cytology practice., Conclusions: Utilization of digital pathology is limited in cytology laboratories as compared to surgical pathology. However, as more laboratories are willing to implement digital cytology in the near future, the establishment of practical clinical guidelines is needed., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: A major barrier to the incorporation of biometric data into clinical practice is the lack of device integration with electronic medical records (EMRs). We developed infrastructure to transmit biometric data from an Apple Watch into the EMR for physician review. The study objective was to test feasibility of using this infrastructure for patients undergoing radiotherapy., Methods: The study included patients with breast or prostate cancer receiving ≥3 weeks of radiotherapy who reported owning an Apple Watch. Daily resting heart rate (HR), HR variability, step count, and exercise minutes were automatically transferred to our EMR using a custom app installed on each patient's iPhone. Biometric data were presented to the treating radiation oncologist for review on a weekly basis during creation of the on-treatment note. Feasibility was defined a priori as physician review of biometric data for at least 90% of patients. Time trends in biometric data were tested using the Jonckheere-Terpstra test. Patient satisfaction was assessed using the System Usability Scale (SUS), with scores above 80 considered above-average user experience., Results: Of the 20 patients enrolled, biometric data were successfully transmitted to the EMR and reviewed by the radiation oncologist for 95% (n = 19) of patients, thus meeting the a priori feasibility threshold. For patients with radiation courses ≥4 weeks, exercise minutes decreased over time ( P = .01) and daily mean HR variability increased over time ( P = .02). The median SUS was 82.5 (IQR, 70-87.5)., Conclusion: Our study demonstrates the feasibility of real-time integration of biometric data collected from an Apple Watch into the EMR with subsequent physician review. The high rates of physician review and patient satisfaction provide support for further development of large-scale collection of wearable device data.

Background: Long-chain PUFA (LC-PUFA) influence varying aspects of inflammation. One mechanism by which they regulate inflammation is by controlling the size and molecular composition of lipid rafts. Lipid rafts are sphingolipid/cholesterol-enriched plasma membrane microdomains that compartmentalize signaling proteins and thereby control downstream inflammatory gene expression and cytokine production., Objectives: This review summarizes developments in our understanding of how LC-PUFA acyl chains of phospholipids, in addition to oxidized derivatives of LC-PUFAs such as oxidized 1-palmitoyl-2-arachidonyl-phosphatidylcholine (oxPAPC), manipulate formation of lipid rafts and thereby inflammation., Methods: We reviewed the literature, largely from the past 2 decades, on the impact of LC-PUFA acyl chains and oxidized products of LC-PUFAs on lipid raft biophysical organization of myeloid and lymphoid cells. The majority of the studies are based on rodent or cellular experiments with supporting mechanistic studies using biomimetic membranes and molecular dynamic simulations. These studies have focused largely on the LC-PUFA docosahexaenoic acid, with some studies addressing eicosapentaenoic acid. A few studies have investigated the role of oxidized phospholipids on rafts., Results: The biophysical literature suggests a model in which n-3 LC-PUFAs, in addition to oxPAPC, localize predominately to nonraft regions and impart a disordering effect in this environment. Rafts become larger because of the ensuing increase in the difference in order between raft and nonrafts. Biochemical studies suggest that some n-3 LC-PUFAs can be found within rafts. This deviation from homeostasis is a potential trigger for controlling aspects of innate and adaptive immunity., Conclusion: Overall, select LC-PUFA acyl chains and oxidized acyl chains of phospholipids control lipid raft dynamics and downstream inflammation. Gaps in knowledge remain, particularly on underlying molecular mechanisms by which plasma membrane receptor organization is controlled in response to oxidized LC-PUFA acyl chains of membrane phospholipids. Validation in humans is also an area for future study., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Docosahexaenoic acid (DHA) controls the biophysical organization of plasma membrane sphingolipid/cholesterol-enriched lipid rafts to exert anti-inflammatory effects, particularly in lymphocytes. However, the impact of DHA on the spatial arrangement of alveolar macrophage lipid rafts and inflammation is unknown., Objectives: The primary objective was to determine how DHA controls lipid raft organization and function of alveolar macrophages. As proof-of-concept, we also investigated DHA's anti-inflammatory effects on select pulmonary inflammatory markers with a murine influenza model., Methods: MH-S cells, an alveolar macrophage line, were treated with 50 μM DHA or vehicle control and were used to study plasma membrane molecular organization with fluorescence-based methods. Biomimetic membranes and coarse grain molecular dynamic (MD) simulations were employed to investigate how DHA mechanistically controls lipid raft size. qRT-PCR, mass spectrometry, and ELISAs were used to quantify downstream inflammatory signaling transcripts, oxylipins, and cytokines, respectively. Lungs from DHA-fed influenza-infected mice were analyzed for specific inflammatory markers., Results: DHA increased the size of lipid rafts while decreasing the molecular packing of the MH-S plasma membrane. Adding a DHA-containing phospholipid to a biomimetic lipid raft-containing membrane led to condensing, which was reversed with the removal of cholesterol. MD simulations revealed DHA nucleated lipid rafts by driving cholesterol and sphingomyelin into rafts. Downstream of the plasma membrane, DHA lowered the concentration of select inflammatory transcripts, oxylipins, and IL-6 secretion. DHA lowered pulmonary Il6 and Tnf-α mRNA expression and increased anti-inflammatory oxylipins of influenza-infected mice., Conclusions: The data suggest a model in which the localization of DHA acyl chains to nonrafts is driving sphingomyelin and cholesterol molecules into larger lipid rafts, which may serve as a trigger to impede signaling and lower inflammation. These findings also identify alveolar macrophages as a target of DHA and underscore the anti-inflammatory properties of DHA for lung inflammation., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Molecular testing (MT) has become standard practice to more accurately rule out malignancy in indeterminate Bethesda III (BIII) thyroid lesions. We sought to assess the adoption of this technology and its impact on cytology reporting, malignancy yield, and rates of surgery across community and academic sites affiliated with a tertiary medical center. Methods: We performed a retrospective cross-sectional study including all fine-needle aspirations (FNAs) analyzed at our institution from 2017 to 2021. We analyzed trends in MT utilization by platform and by community or academic site. We compared BIII call rates, MT utilization rates, rates of subsequent surgery, and malignancy yield on final pathology before and after MT became readily available using chi-square analysis and linear regression. Results: A total of 8960 FNAs were analyzed at our institution from 2017 to 2021. There was broad adoption of MT across both community and academic sites. There was a significant increase in both the BIII rate and the utilization of MT between the pre- and post-MT periods ( p  < 0.001 and p  < 0.001). There was no significant change in the the malignancy yield on final pathology (57.1% vs. 50.0%, p  = 0.347), while the positive predictive value of MT decreased from 85% to 50% ( p  = 0.008 [confidence interval 9.5-52.5% decrease]). Conclusions: The use of MT increased across the institution over the study period, with the largest increase seen after a dedicated pass for MT was routinely collected. This increased availability of MT may have led to an unintended increase in the rates of BIII lesions, MT utilization, and surgery for benign nodules. Physicians who use MT should be aware of potential consequences of its adoption to appropriately counsel patients.

Digital cytology and artificial intelligence (AI) are gaining greater adoption in the cytology laboratory. However, peer-reviewed real-world data and literature are lacking in regard to the current clinical landscape. The American Society of Cytopathology in conjunction with the International Academy of Cytology and the Digital Pathology Association established a special task force comprising 20 members with expertise and/or interest in digital cytology. The aim of the group was to investigate the feasibility of incorporating digital cytology, specifically cytology whole slide scanning and AI applications, into the workflow of the laboratory. In turn, the impact on cytopathologists, cytologists (cytotechnologists), and cytology departments were also assessed. The task force reviewed existing literature on digital cytology, conducted a worldwide survey, and held a virtual roundtable discussion on digital cytology and AI with multiple industry corporate representatives. This white paper, presented in 2 parts, summarizes the current state of digital cytology and AI practice in global cytology practice. Part 1 of the white paper is presented as a separate paper which details a review and best practice recommendations for incorporating digital cytology into practice. Part 2 of the white paper presented here provides a comprehensive review of AI in cytology practice along with best practice recommendations and legal considerations. Additionally, the cytology global survey results highlighting current AI practices by various laboratories, as well as current attitudes, are reported., (Copyright © 2023 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Digital cytology and artificial intelligence (AI) are gaining greater adoption in the cytopathology laboratory. However, peer-reviewed real-world data and literature are lacking regarding the current clinical landscape. The American Society of Cytopathology in conjunction with the International Academy of Cytology and the Digital Pathology Association established a special task force comprising 20 members with expertise and/or interest in digital cytology. The aim of the group was to investigate the feasibility of incorporating digital cytology, specifically cytology whole slide scanning and AI applications, into the workflow of the laboratory. In turn, the impact on cytopathologists, cytologists (cytotechnologists), and cytology departments were also assessed. The task force reviewed existing literature on digital cytology, conducted a worldwide survey, and held a virtual roundtable discussion on digital cytology and AI with multiple industry corporate representatives. This white paper, presented in 2 parts, summarizes the current state of digital cytology and AI practice in global cytology practice. Part 1 of the white paper presented herein is a review and offers best practice recommendations for incorporating digital cytology into practice. Part 2 of the white paper provides a comprehensive review of AI in cytology practice along with best practice recommendations and legal considerations. Additionally, the results of a global survey regarding digital cytology are highlighted., (Copyright © 2023 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

When compared to other malignancies, the tumor microenvironment (TME) of primary and castration-resistant prostate cancer (CRPC) is relatively devoid of immune infiltrates. While androgen deprivation therapy (ADT) induces a complex immune infiltrate in localized prostate cancer, the composition of the TME in metastatic castration-sensitive prostate cancer (mCSPC), and the effects of ADT and other treatments in this context are poorly understood. Here, we perform a comprehensive single-cell RNA sequencing (scRNA-seq) profiling of metastatic sites from patients participating in a phase 2 clinical trial (NCT03951831) that evaluated standard-of-care chemo-hormonal therapy combined with anti-PD-1 immunotherapy. We perform a longitudinal, protein activity-based analysis of TME subpopulations, revealing immune subpopulations conserved across multiple metastatic sites. We also observe dynamic changes in these immune subpopulations in response to treatment and a correlation with clinical outcomes. Our study uncovers a therapy-resistant, transcriptionally distinct tumor subpopulation that expands in cell number in treatment-refractory patients., Competing Interests: Declaration of interests Dr. Hawley has served as a paid consultant to Seagen, Daiichi Sankyo, and ImmunityBio and has received sponsored research funding to her institution from Astra Zeneca, Bristol Meyers Squibb, Crescendo Biologics, Macrogenics, and Vaccitech. Dr. Drake is a co-inventor on patents licensed from JHU to BMS and Janssen and is currently an employee of Janssen Research. Dr. Califano is founder, equity holder, and consultant of DarwinHealth Inc., a company that has licensed some of the algorithms used in this manuscript from Columbia University. Columbia University is also an equity holder in DarwinHealth Inc. Dr. Lowy is an employee and stockholder of Regeneron Pharmaceuticals., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: The arachnoid often bulges prematurely during surgical excision of large pituitary tumors obscuring the deeper regions and crevices preventing total excision. Pushing the arachnoid may not be helpful and may tear it inadvertently and extensively leading to complications. We have described controlled arachnoid opening in large pituitary macroadenomas during the final stages of excision to gain access to the hidden portions and compared our results to the conventional technique., Patients and Methods: Patients with pituitary macroadenoma of Hardy's III and KNOSP II in whom arachnoid had bulged prematurely were considered for study. They were grouped temporally. In first group ( n  = 12), the arachnoid was pushed to retrieve the tumor and in the second group ( n  = 10) it was punctured to aid resection. The extent of resection was assessed on postoperative scans, and complications in both groups, were noted., Results: In the first group where arachnoid was pushed to retrieve tumor, Gross Total Resection (GTR) could be achieved in 5 patients. Inadvertent large arachnoid tear occurred in 3 patients of which, 2 developed CSF Rhinorrhoea. No patient had neurovascular injury.In the second group, GTR could be achieved in all without any added complications., Conclusion: Deliberate needle puncture and controlled drainage of CSF from arachnoid that bulges prematurely while endoscopic Transsphenoidal surgery for large pituitary tumors is a safe and effective method to gain access to the hidden portions of tumor to achieve GTR.

Dysregulation of glucose metabolism in response to diet-induced obesity contributes toward numerous complications, such as insulin resistance and hepatic steatosis. Therefore, there is a need to develop effective strategies to improve glucose homeostasis. In this review, we first discuss emerging evidence from epidemiological studies and rodent experiments that increased consumption of EPA (either as oily fish, or dietary/pharmacological supplements) may have a role in preventing impairments in insulin and glucose homeostasis. We then review the current evidence on how EPA-derived metabolites known as hydroxyeicosapentaenoic acids (HEPEs) may be a major mode of action by which EPA exerts its beneficial effects on glucose and lipid metabolism. Notably, cell culture and rodent studies show that HEPEs prevent fat accumulation in metabolic tissues through peroxisome proliferator activated receptor (PPAR)-mediated mechanisms. In addition, activation of the resolvin E1 pathway, either by administration of EPA in the diet or via intraperitoneal administration of resolvin E1, improves hyperglycemia, hyperinsulinemia, and liver steatosis through multiple mechanisms. These mechanisms include shifting immune cell phenotypes toward resolution of inflammation and preventing dysbiosis of the gut microbiome. Finally, we present the next steps for this line of research that will drive future precision randomized clinical trials with EPA and its downstream metabolites. These include dissecting the variables that drive heterogeneity in the response to EPA, such as the baseline microbiome profile and fatty acid status, circadian rhythm, genetic variation, sex, and age. In addition, there is a critical need to further investigate mechanisms of action for HEPEs and to establish the concentration of HEPEs in differing tissues, particularly in response to consumption of oily fish and EPA-enriched supplements., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Obesity exacerbates inflammation upon lung injury; however, the mechanisms by which obesity primes pulmonary dysregulation prior to external injury are not well studied. Herein, we tested the hypothesis that obesity dysregulates pulmonary PUFA metabolism that is central to inflammation initiation and resolution. We first show that a high-fat diet (HFD) administered to C57BL/6J mice increased the relative abundance of pulmonary PUFA-containing triglycerides and the concentration of PUFA-derived oxylipins (particularly prostaglandins and hydroxyeicosatetraenoic acids), independent of an increase in total pulmonary PUFAs, prior to onset of pulmonary inflammation. Experiments with a genetic model of obesity (ob/ob) generally recapitulated the effects of the HFD on the pulmonary oxylipin signature. Subsequent pulmonary next-generation RNA sequencing identified complex and unique transcriptional regulation with the HFD. We found the HFD increased pathways related to glycerophospholipid metabolism and immunity, including a unique elevation in B cell differentiation and signaling. Furthermore, we conducted computational integration of lipidomic with transcriptomic data. These analyses identified novel HFD-driven networks between glycerophospholipid metabolism and B cell receptor signaling with specific PUFA-derived pulmonary oxylipins. Finally, we confirmed the hypothesis by demonstrating that the concentration of pulmonary oxylipins, in addition to inflammatory markers, were generally increased in mice consuming a HFD upon ozone-induced acute lung injury. Collectively, these data show that a HFD dysregulates pulmonary PUFA metabolism prior to external lung injury, which may be a mechanism by which obesity primes the lungs to respond poorly to infectious and/or inflammatory challenges., Competing Interests: Conflicts of interest S. R. S. has received industry support on projects and conferences related to n-3 fatty acids from Metagenics Inc., and the Wiley Companies., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Canada and the United States continue to experience increasing overdose deaths attributed to highly toxic illicit substances, driven by fentanyl and its analogues. Many bystanders report being hesitant to call 9-1-1 at an overdose due to fears around police presence and arrests. In Canada, a federal law was enacted in 2017, the Good Samaritan Drug Overdose Act (GSDOA), to provide protection from simple drug possession and related charges when 9-1-1 is called to an overdose. There is limited evidence, however, that the GSDOA has improved rates of intention to call 9-1-1 at overdose events. We therefore sought to examine intent to call 9-1-1 among persons who received GSDOA education and were at risk of witnessing an overdose., Methods: A cross-sectional survey was conducted with people at risk of witnessing an overdose recruited at 19 Take Home Naloxone (THN) program sites across British Columbia as well as online through Foundry from October 2020 to April 2021. Descriptive statistics were used to examine intention to call 9-1-1 at future overdoses. Multivariable logistic regression models were built in hierarchical fashion to examine factors associated with intention to call 9-1-1., Results: Overall, 89.6% (n = 404) of the eligible sample reported intention to call 9-1-1. In the multivariable model, factors positively associated with intention to call 9-1-1 included identifying as a cisgender woman (adjusted odds ratio [AOR]: 3.37; 95% CI: 1.19-9.50) and having previous GSDOA awareness ([AOR]: 4.16; 95% CI: 1.62-10.70). Having experienced a stimulant overdose in the past 6 months was negatively associated with intention to call 9-1-1 ([AOR]: 0.24; 95% CI: 0.09-0.65)., Conclusion: A small proportion of the respondents reported that, despite the enactment of GSDOA, they did not intend to call 9-1-1 and those who were aware of the act were more likely to report an intention to call at future overdose events. Increasing GSDOA awareness and/or additional interventions to support the aims of the GSDOA could address ongoing reluctance to seek emergency medical care by people who use drugs., (© 2022. The Author(s).)

Based on coping theory, the current research examines how and why COVID-19 phobia affects frontline healthcare professionals' mental health, as well as their burnout and work-related stress. We focused on the mediating role of burnout and work-related stress in this study. In the current study, we also examined the moderating influence of healthcare professionals' handwashing behavior using the Hayes Process model. We employed a daily diary approach to collect data from respondents in Pakistan's frontline healthcare professionals ( n = 79, 79 × 10 = 790) who were directly treating COVID-19 patients during the omicron wave. According to the findings of the study, COVID-19 phobia significantly disturbs healthcare professionals' mental health, as well as significantly strengthens burnout and work-related stress. The findings also demonstrated that burnout significantly negatively influences mental health. The mediation influence of burnout and work-related stress in the association between COVID-19 phobia and mental health has shown to be significant. The moderation analysis revealed that high handwashing behavior significantly buffers the negative impact of COVID-19 phobia, as well as the adverse effect of burnout on healthcare professionals' mental health. Moreover, our findings have theoretical and managerial implications, as well as new research directions for scholars to understand the adverse impact of daily obstacles on professionals' (nurses and doctors, etc.) mental health and work performance, as well as issues based on resource conversation philosophy.

Resolvin E1 (RvE1), a specialized pro-resolving mediator (SPM), improves glucose homeostasis in inbred mouse models of obesity. However, an impediment toward translation is that obesity is a highly heterogenous disease in which individuals will respond very differently to interventions such as RvE1. Thus, there is a need to study SPMs in the context of modeling the heterogeneity of obesity that is observed in humans. We investigated how RvE1 controls the concentration of key circulating metabolic biomarkers using diversity outbred (DO) mice, which mimic human heterogeneity. We first demonstrate that weights of DO mice can be classified into distinct distributions of fat mass (i.e., modeling differing classes of obesity) in response to a high-fat diet and in the human population when examining body composition. Next, we show RvE1 administration based on body weight for four consecutive days after giving mice a high-fat diet led to approximately half of the mice responding positively for serum total gastric inhibitory polypeptide (GIP), glucagon, insulin, glucose, leptin, and resistin. Interestingly, RvE1 improved hyperleptinemia most effectively in the lowest class of fat mass despite adjusting the dose of RvE1 with increasing adiposity. Furthermore, leptin levels after RvE1 treatment were the lowest in those mice that were also RvE1 positive responders for insulin and resistin. Collectively, these results suggest a therapeutic fat mass-dependent window for RvE1, which should be considered in future clinical trials. Moreover, the data underscore the importance of studying SPMs with heterogenous mice as a step toward precision SPM administration in humans., (© 2022 Federation of American Societies for Experimental Biology.)

Improved understanding of local breast biology that favors the development of estrogen receptor negative (ER-) breast cancer (BC) would foster better prevention strategies. We have previously shown that overexpression of specific lipid metabolism genes is associated with the development of ER- BC. We now report results of exposure of MCF-10A and MCF-12A cells, and mammary organoids to representative medium- and long-chain polyunsaturated fatty acids. This exposure caused a dynamic and profound change in gene expression, accompanied by changes in chromatin packing density, chromatin accessibility, and histone posttranslational modifications (PTMs). We identified 38 metabolic reactions that showed significantly increased activity, including reactions related to one-carbon metabolism. Among these reactions are those that produce S-adenosyl-L-methionine for histone PTMs. Utilizing both an in-vitro model and samples from women at high risk for ER- BC, we show that lipid exposure engenders gene expression, signaling pathway activation, and histone marks associated with the development of ER- BC., (© 2022. The Author(s).)