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Tim Mercer,1 Alice C Chang,2 Lydia Fischer,3 Adrian Gardner,4–6 Immaculate Kerubo,7,8 Dan N Tran,7,9 Jeremiah Laktabai,10 Sonak Pastakia7,9 1Department of Population Health, The University of Texas at Austin Dell Medical School, Austin, TX 78712, USA; 2Genentech Inc., San Francisco, CA, USA; 3Department of Child Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA; 4Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; 5Department of Medicine, Moi University School of Medicine, Eldoret, Kenya; 6Indiana Institute for Global Health, Indianapolis, IN 46202, USA; 7Department of Pharmacology and Toxicology, Moi University School of Medicine, Eldoret, Kenya; 8National Spinal Injury Referral Hospital, Nairobi, Kenya; 9Department of Pharmacy Practice, Purdue University College of Pharmacy, Purdue Kenya Partnership P.O. Box 5760, Eldoret 30100, Kenya; 10Department of Family Medicine, Moi University School of Medicine, Eldoret, KenyaCorrespondence: Sonak PastakiaDepartment of Pharmacy Practice, Purdue Kenya Partnership, Purdue University College of Pharmacy, P.O. Box 5760, Eldoret 30100, KenyaEmail spastaki@gmail.comAbstract: Diabetes is a chronic non-communicable disease (NCD) presenting growing health and economic burdens in sub-Saharan Africa (SSA). Diabetes is unique due to its cross-cutting nature, impacting multiple organ systems and increasing the risk for other communicable and non-communicable diseases. Unfortunately, the quality of care for diabetes in SSA is poor, largely due to a weak disease management framework and fragmented health systems in most sub-Saharan African countries. We argue that by synergizing disease-specific vertical programs with system-specific horizontal programs through an integrated disease-system diagonal approach, we can improve access, quality, and safety of diabetes care programs while also supporting other chronic diseases. We recommend utilizing the six World Health Organization (WHO) health system building blocks – 1) leadership and governance, 2) financing, 3) health workforce, 4) health information systems, 5) supply chains, and 6) service delivery – as a framework to design a diagonal approach with a focus on health system strengthening and integration to implement and scale quality diabetes care. We discuss the successes and challenges of this approach, outline opportunities for future care programming and research, and highlight how this approach can lead to the improvement in the quality of care for diabetes and other chronic diseases across SSA.Keywords: diabetes, sub-Saharan African, integrated diagonal health systems approach, health system building blocks, health system strengthening, health system integration

Geoffrey W Siegel,1 J Sybil Biermann,1 Rashmi Chugh,2 Jon A Jacobson,3 David Lucas,4 Mary Feng,5 Andrew C Chang,6 Sean R Smith,7 Sandra Wong,6 Jill L Hasen1 1Department of Orthopedics, 2Department of Medical Oncology, 3Department of Radiology, 4Department of Pathology, 5Department of Radiation, 6Department of Surgery, 7Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA Abstract: The rarity of bone and soft tissue sarcoma, the difficulty in interpretation of imaging and histology, the plethora of treatment modalities, and the complexity and intensity of the treatment contribute to the need for systematic multidisciplinary team management of patients with these diseases. An integrated multidisciplinary clinic and team with a structured sarcoma tumor board facilitate team coordination and communication. This paper reviews the rationale for multidisciplinary management of sarcoma and details the operational structure of the Multidisciplinary Sarcoma Clinic and Sarcoma Tumor Board. The structured Multidisciplinary Sarcoma Tumor Board provides opportunity for improvement in logistics, teaching, quality, and enrollment in clinical trials. Keywords: sarcoma, sarcoma care, sarcoma tumor board, collaborative approach

Eco-friendly aquaculture technology has become a major global trend in recent years. This study's investigation and analysis revealed that eco-friendly aquaculture management technologies increased the production per unit area of the grouper and the fourfinger threadfin. From an economic perspective, it was estimated that the application of eco-friendly aquaculture management technology might increase grouper production by 18.6 metric tons/ha and the output value by US$7,106.9/ha per year, as well as decrease electricity consumption by 1,510.45 kWh/ha/month. It was estimated that for fourfinger threadfin, the use of eco-friendly aquaculture management technologies might increase the production by 10.1 tons/ha and the output value by US$5,031.8/ha each year, as well as reduce the electricity consumption by 257.18 kWh/ha/month. As such, eco-friendly aquaculture management technologies may increase the output value while reducing energy consumption and costs. Furthermore, regression analysis with dummy variables showed that factors affecting grouper production per unit area included applying eco-friendly aquaculture management technology, stocking density, and harvest specifications. However, no significant relationship was identified between breeding time and production per unit area, and the correlation coefficient was negative. The main factors positively affecting the production per unit area of the fourfinger threadfin were stocking density, the application of eco-friendly aquaculture management technology, and harvest specifications. However, a longer breeding time did not result in better production per unit area. This study showed that eco-friendly aquaculture management technology increased the production per unit area and reduced water consumption, electricity consumption, and operating costs to promote sustainable use of water and land resources and sustainable industrial operation and 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 © 2024 Elsevier Ltd. All rights reserved.)

Breast cancer affects 1/8 of women throughout their lifetimes, with 90% of cancer deaths being caused by metastasis. However, metastasis poses unique challenges to research, as complex changes in the microenvironment in different metastatic sites and difficulty obtaining tissue for study hinder the ability to examine in depth the changes that occur during metastasis. Rapid autopsy programs thus fill a unique need in advancing metastasis research. Here, we describe our protocol and processes for establishing and improving the US-based Hope for OTHERS (Our Tissue Helping Enhance Research and Science) program for organ donation in metastatic breast cancer. Our results reveal key logistical and protocol improvements that are uniquely beneficial to certain programs based on identifiable features, such as working closely with patient advocates, methods to rescue RNA quality in cases where tissue quality may degrade due to time delays, as well as guidelines and future expansions of our program with new research and novel research findings in patient outcomes, metastatic phylogeny, living model development and more., Competing Interests: Conflict of Interest Statement The authors have no conflicts of interest related to this work. Author RB is a former consultant for GE Health (now ended), and current Speaker’s Bureau member for AstraZeneca. Author AB is a current consultant for AstraZeneca, Pfizer, Novartis, Lilly, Genentech/Roche, Daiichi Sankyo, Merck, Agendia, Sanofi, Puma, Myriad, Gilead, Bria-Cell, and receives research support from Agendia and AstraZeneca.

Cd ions are absorbed and transported from the soil by crop roots, which are the first organ to be exposed to Cd. This results in an increase in cadmium ions in crops, significantly affecting crop growth and yield. Exogenous melatonin (MT) can help reduce cadmium (Cd) stress in cotton, but the specific contribution of roots to this process remains unclear. In order to address this knowledge gap, an in-situ root phenotyping study was conducted to investigate the the phenotype and lifespan of roots under cadmium stress (Cd) and melatonin treatment (Cd + MT). The results showed that MT alleviated the decreases in plant height, leaf area, SPAD value, stem diameter, stomatal conductance and net photosynthetic rate under Cd stress, which further promoted the biomass accumulation in various cotton organs. What is more, the Cd + MT treatment increased root volume, surface area, and length under Cd stress by 25.63 %, 10.58 %, and 21.89 %, respectively, compared with Cd treatment. Interestingly, compared to Cd treatment, Cd + MT treatment also significantly extended the lifespan of roots and root hairs by 6.68 days and 2.18 days, respectively. In addition, Cd + MT treatment reduced the transport of Cd from roots to shoots, particularly to bolls, and decreased the Cd bioconcentration factor in bolls by 61.17 %, compared to Cd treatment. In conclusion, these findings show that applying MT externally helps reduce Cd stress by delaying root senescence, promoting root development and regulating Cd transport. This method can be an effective approach to managing Cd stress in cotton., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Cystathionine γ-lyase (CSE) is a major enzyme that produces hydrogen sulfide (H 2 S). Herein, we report how CSE plays a previously unknown role in regulating the antioxidant effects of the mitochondria in human umbilical vein endothelial cells by releasing H 2 S nearby under stress conditions. We found that H 2 S partially promoted angiogenesis in the endothelial cells through the AKT/nuclear factor erythroid 2-related factor 2 (AKT/NRF2) signaling pathway. H 2 S improved mitochondrial function by altering the expressions of the mitofusin2 and dynamin-1-like mitochondrial fission proteins to inhibit oxidative stress and enhance NRF2 nuclear translocation. CSE is located only in the cytoplasm and not in the mitochondria, but it is transported to the vicinity of the mitochondria to produce H 2 S, which plays an antioxidant role in human umbilical vein endothelial cells under stress. The CSE mutant (with mutated CSE activity center: CSE D187A ) partially decreased the effects on promoting angiogenesis, resisting oxidative stress, and entering the mitochondria. These results show that CSE translocation is a unique mechanism that promotes H 2 S production inside the mitochondria under stress stimulation. Therefore, the CSE mutant site (CSE D187A ) may be a potential target for drug therapy., 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 Xiao, Chen, Yan, Zheng, Qiu, Lin, Zong, Chang, Yu Chang, Wu and Hou.)

Mitochondria are the cellular energy hub and central target of metabolic regulation. Mitochondria also facilitate proteostasis through pathways such as the 'mitochondria as guardian in cytosol' (MAGIC) whereby cytosolic misfolded proteins (MPs) are imported into and degraded inside mitochondria. In this study, a genome-wide screen in Saccharomyces cerevisiae uncovered that Snf1, the yeast AMP-activated protein kinase (AMPK), inhibits the import of MPs into mitochondria while promoting mitochondrial biogenesis under glucose starvation. We show that this inhibition requires a downstream transcription factor regulating mitochondrial gene expression and is likely to be conferred through substrate competition and mitochondrial import channel selectivity. We further show that Snf1/AMPK activation protects mitochondrial fitness in yeast and human cells under stress induced by MPs such as those associated with neurodegenerative diseases., Competing Interests: YW, LR, JZ, XZ, AC, AT, RL No competing interests declared, (© 2023, Wang, Ruan et al.)

Background: Gender and geographic access to care play a large role in health disparities in esophageal cancer care. The aim of our study was to evaluate disparities in peri-operative outcomes for patients undergoing esophagectomy based on gender and geographic location., Methods: A retrospective cohort of prospectively collected data from patients who underwent esophagectomy from 2003 to 2022 was identified and analyzed based on gender and county, which were aggregated into existing state-level "metropolitan" versus "rural" designations. The demographics, pre-operative treatment, surgical complications, post-operative outcomes, and length of stay (LOS) of each group were analyzed using chi-squared, paired t -tests and single-factor ANOVA., Results: Of the 1545 patients, men (83.6%) and women (16.4%) experienced similar rates of post-operative complications, but women experienced significantly longer hospital ( p = 0.002) and ICU ( p = 0.03) LOSs as compared with their male counterparts, with no differences in 30-day mortality. When separated by geographic criteria, rural women were further outliers, with significantly longer hospital LOSs ( p < 0.001) and higher rates of ICU admission ( p < 0.001)., Conclusions: Rural female patients undergoing esophagectomy were more likely to have a longer inpatient recovery process compared with their female metropolitan or male counterparts, suggesting a need for more targeted interventions in this population.

Cellular metabolism plays an essential role in the regrowth and regeneration of a neuron following physical injury. Yet, our knowledge of the specific metabolic pathways that are beneficial to neuron regeneration remains sparse. Previously, we have shown that modulation of O-linked β-N-acetylglucosamine (O-GlcNAc) signaling, a ubiquitous post-translational modification that acts as a cellular nutrient sensor, can significantly enhance in vivo neuron regeneration. Here, we define the specific metabolic pathway by which O-GlcNAc transferase ( ogt-1 ) loss of function mediates increased regenerative outgrowth. Performing in vivo laser axotomy and measuring subsequent regeneration of individual neurons in C. elegans , we find that glycolysis, serine synthesis pathway (SSP), one-carbon metabolism (OCM), and the downstream transsulfuration metabolic pathway (TSP) are all essential in this process. The regenerative effects of ogt-1 mutation are abrogated by genetic and/or pharmacological disruption of OCM and the SSP linking OCM to glycolysis. Testing downstream branches of this pathway, we find that enhanced regeneration is dependent only on the vitamin B12 independent shunt pathway. These results are further supported by RNA sequencing that reveals dramatic transcriptional changes by the ogt-1 mutation, in the genes involved in glycolysis, OCM, TSP, and ATP metabolism. Strikingly, the beneficial effects of the ogt-1 mutation can be recapitulated by simple metabolic supplementation of the OCM metabolite methionine in wild-type animals. Taken together, these data unearth the metabolic pathways involved in the increased regenerative capacity of a damaged neuron in ogt-1 animals and highlight the therapeutic possibilities of OCM and its related pathways in the treatment of neuronal injury., Competing Interests: DY, AC, NG, SC, CG No competing interests declared, (© 2024, Yadav et al.)

Background: The use of telehealth has grown exponentially since the COVID-19 pandemic. The safety of an initial telehealth preoperative evaluation for patients undergoing general thoracic procedures is unknown., Methods: We retrospectively reviewed all patients who underwent a general thoracic surgical procedure at our academic tertiary care institution from January 2021 to December 2022. We determined that visits were performed through telehealth or an in-person visit and linked to our institutional Society of Thoracic Surgeons database to abstract outcomes. Our outcomes of interest included complications, readmissions, intraoperative conversions, and intensive care unit admissions. Hierarchical multivariate logistic regression was used and clustered within procedure type., Results: Of 1348 patients who underwent a procedure in our institution, 469 (34.8%) patients had an initial telehealth preoperative evaluation. We analyzed outcomes for 757 patients who underwent a major thoracic procedure. Patients who had an in-person visit tended to be older with worse functional status. After multivariable adjustment, an initial telehealth evaluation was associated with a lower adjusted complication rate (31.6% vs 40.4%; odds ratio, 0.63 [95% CI, 0.46-0.88]; P  = .006), with no significant difference in readmissions, intensive care unit admissions, or intraoperative conversions., Conclusions: This preliminary study of the use of telehealth for preoperative evaluation of patients undergoing general thoracic procedures suggests that it is a safe and feasible alternative to an in-person evaluation. Care must be taken to ensure that this pandemic-induced trend continues to improve patient access to surgical care without worsening or creating new disparities., (© 2024 The Author(s).)

Background: Neoadjuvant chemoradiation with esophagectomy is standard management for locally advanced esophageal cancer. Studies have shown that surgical timing following chemoradiation is important for minimizing postoperative complications, however in practice timing is often variable and delayed. Although postoperative impact of surgical timing has been studied, less is known about factors associated with delays., Materials and Methods: A retrospective review was performed for 96 patients with esophageal cancer who underwent chemoradiation then esophagectomy between 2018 and 2020 at a single institution. Univariable and stepwise multivariable analyses were used to assess association between social (demographics, insurance) and clinical variables (pre-operative weight, comorbidities, prior cardiothoracic surgery, smoking history, disease staging) with time to surgery (≤8 weeks "on-time" vs. >8 weeks "delayed")., Results: Fifty-one patients underwent esophagectomy within 8 weeks of chemoradiation; 45 had a delayed operation. Univariate analysis showed the following characteristics were significantly different between on-time and delayed groups: weight loss within 3 months of surgery (3.9 ± 5.1 kg vs. 1.5 ± 3.6 kg; P = 0.009), prior cardiovascular disease (29% vs. 49%; P = 0.05), prior cardiothoracic surgery (4% vs. 22%; P = 0.01), history of ever smoked (69% vs. 87%; P = 0.04), absent nodal metastasis on pathology (57% vs. 82%; P = 0.008). Multivariate analysis demonstrated that prior cardiothoracic surgery (OR 8.924, 95%CI 1.67-47.60; P = 0.01) and absent nodal metastasis (OR 4.186, 95%CI 1.50-11.72; P = 0.006) were associated with delayed surgery., Conclusions: Delayed esophagectomy following chemoradiotherapy is associated with prior cardiothoracic surgery and absent nodal metastasis. Further investigations should focus on understanding how these factors contribute to delays to guide treatment planning and mitigate sources of outcome disparities., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Sidra Bonner receives funding from the 10.13039/100000002NIH T32 Multidisciplinary Program in Lung Disease at the 10.13039/100007270University of Michigan If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Despite advances in operative techniques and postoperative care, esophagectomy remains a morbid operation. Leveraging complication epidemiology and the correlation of these complications may improve rescue and refine early recovery pathways., Methods: This study retrospectively reviewed all esophagectomies performed at a tertiary academic center from 2014 to 2021 and quantified the timing of the most common complications. Daily incidence values for index complications were calculated, and a covariance matrix was created to examine the correlation of the complications with each other. Study investigators performed a Cox proportional hazards analysis to clarify the association between early diagnosis of postoperative atrial fibrillation and pneumonia with subsequent anastomotic leak., Results: The study analyzed 621 esophagectomies, with 580 (93.4%) cervical anastomoses and 474 (76%) patients experiencing complications. A total of 159 (25.6%) patients had postoperative atrial fibrillation, and 155 (25.0%) had an anastomotic leak. The median (interquartile range [IQR]) postoperative day of these complications was day 2 (IQR, days 2-3) and day 8 (IQR, days 7-11), respectively. Our covariance matrix found significant associations in the variance of the most common postoperative complications, including pneumonia, atrial fibrillation, anastomotic leak, and readmissions. Early postoperative atrial fibrillation (hazard ratio, 8.1; 95% CI, 5.65-11.65) and postoperative pneumonia (hazard ratio, 3.8; 95% CI, 1.98-7.38) were associated with anastomotic leak., Conclusions: Maintaining a high index of suspicion for early postoperative complications is crucial for rescuing patients after esophagectomy. Early postoperative pneumonia and atrial fibrillation may be sentinel complications for an anastomotic leak, and their occurrence may be used to prompt further clinical investigation. Early recovery protocols should consider the development of early complications into postoperative feeding and imaging algorithms., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Data are scarce on whether the composition of the lung microbiome (extending from the nasopharynx to the peripheral lung tissue) varies according to histology or grade of non-small cell lung cancer. We hypothesized that the composition of the lung microbiome would vary according to the histology and the grade of non-small cell lung cancer., Methods: We collected naso-oral and central lobar (cancer affected, ipsilateral unaffected, and contralateral unaffected) bronchoalveolar lavage fluid and brushing samples from patients with clinical early-stage lung cancer between July 2018 and February 2020 at a single academic center. We performed bacterial 16S rRNA sequencing and then compared clinical and pathologic findings with microbiome signatures., Results: Samples were collected from 28 patients. Microbial composition in affected lobes displayed unique enrichment of oropharyngeal bacterial species that was significantly different compared with that from the unaffected contralateral lobes; patients with chronic obstructive pulmonary disease had similar diversity to those without chronic obstructive pulmonary disease ( P  = .1312). The lung microbiome diversity in patients with adenocarcinoma was similar to those with squamous cell cancer ( P  = .27). There were no differences in diversity or composition in the unaffected lobes of patients with adenocarcinoma versus squamous cell cancer. There was a trend toward lower lung microbial diversity in poorly differentiated adenocarcinomas compared with well-differentiated adenocarcinomas ( P  = .08)., Conclusions: The lung microbiota differs between cancer affected and unaffected lobes in the same patient. Furthermore, poorly differentiated lung cancers were associated with lower microbial diversity. Larger studies will be required to confirm these findings., Competing Interests: Dr Reddy has nonrelevant disclosures with Intuitive Surgical, Genentech, On Target Labs, and Medtronic. 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., (© 2023 The Author(s).)

Osteosarcoma is a common malignant tumor in children and adolescents, known for its aggressive invasion and distant metastasis, leading to a poor prognosis. Matrix metalloproteinases (MMPs) can degrade the extracellular matrix and basement membranes through their proteolytic activity, thereby promoting osteosarcoma metastasis. Chemokine ligand 2 (CCL2) is a well-studied chemokine that plays a significant role in the cell motility of many cancers. However, its specific involvement in osteosarcoma metastasis is not fully understood. The aim of this study is to examine the role of miRNAs in CCL2-mediated MMP expression and cell motility in human osteosarcoma. The analysis of immunohistochemistry data and databases associated a positive correlation between CCL2 or MMP-3 levels with the metastasis of osteosarcoma patients. The in vivo lung metastatic osteosarcoma model also demonstrated similar effects, showing higher levels of CCL2 and MMP-3 in lung metastatic osteosarcoma tissues. The stimulation of osteosarcoma cells with CCL2 enhanced migration and invasion abilities through the upregulation of MMP-3 synthesis. Our results also indicate that CCL2 enhances MMP-3-dependent cell motility by inhibiting miR-3659 synthesis. Therefore, CCL2 represents a promising therapeutic target for treating metastasis in osteosarcoma.

Objectives: To investigate the associations of alcohol consumption and smoking with the development of perimetric glaucoma in patients with suspected glaucoma., Design: A retrospective cohort study of patients suspected to have glaucoma enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES)., Setting: Three tertiary glaucoma centres in the USA., Participants: 825 eyes of 610 patients with glaucoma suspect eyes with normal visual fields (VF) at baseline were followed over an average of 9 years from the DIGS and ADAGES studies., Outcome Measures: Development of glaucoma was defined as occurrence of three consecutive abnormal VF tests during follow-up. Univariable and multivariable Cox regression models were used to investigate lifestyle-related factors associated with development of VF loss over time., Results: VF tests were abnormal three times in a row in 235 (28.5%) eyes. Alcohol consumption was associated with a higher risk of developing glaucoma (HR 1.57, 95% CI 1.03 to 2.38, p=0.037). In men, the risk of developing glaucoma in alcohol drinkers (HR 1.92, 95% CI 1.00 to 3.68, p=0.048) was greater than non-alcohol drinkers. In individuals of African descent, the risk of developing glaucoma in alcohol drinkers (HR 1.79, 95% CI 1.02 to 3.15, p=0.043) was greater than non-alcohol drinkers. Age was a modifier of the relationship between smoking and glaucomatous VF defects (p=0.048). The risk of developing glaucoma in smokers (HR 1.73, 95% CI 1.10 to 2.72, p=0.019) was greater than never smokers after adjustment for confounding factors in older patients (age >61 years)., Conclusion: Alcohol consumption was associated with an increased risk of developing glaucoma, particularly in men and individuals of African descent. The risk of developing glaucoma among smokers suspected of having glaucoma was influenced by age, with older individuals having a higher risk than younger people., Trial Registration Number: NCT00221897 and NCT00221923., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is widespread use of pneumatic tourniquet for both upper and lower extremity orthopedic surgeries. Tourniquet use improves visualization, decreases blood loss, and as a result, decreases operative time. Exceeding a certain amount of tourniquet time can cause lasting neuromuscular damage. Orthopedic procedures cause significant pain, and the perioperative narcotic prescriptions after orthopedic surgery have been identified as one of the major contributors to the opioid epidemic. Our aim was to determine whether increasing tourniquet time had a negative impact on immediate postoperative opiate usage in the upper extremity, and to determine other factors associated with increased immediate postoperative opiate usage., Methods: A retrospective medical record review was performed on patients who underwent volar pleading for fracture fixation between January 2014 and December 2019 at a single institution. Postoperative pain, morphine equivalent dose (MED) usage, and demographic variables were collected. Multivariable analysis was performed, with P < .05 considered significant., Results: Immediate postoperative MED consumed was not correlated with operative time, tourniquet time, preoperative substance usage, or sex. However, postoperative MED consumed was correlated with preoperative narcotic use, high body mass index (BMI), and fracture surgery complexity., Conclusions: Tourniquet usage under current guidelines does not appear to have an effect on postoperative pain and narcotic usage. Preoperative narcotic usage, BMI, and surgery complexity are significant factors for postoperative opiate consumption., 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.

The worldwide spreading of severe acute respiratory syndrome SARS-CoV2 pandemic, a massive setback to every human being. In response to strategies actions against Covid-19 spreading many detection, prevention, and post-measures are being studied in large capacities. Association of SARS-CoV2 with ACE2 is well acknowledged and used for developing point-of-care detection kits. Recently, cases and studies have surfaced showing relation of ACE I/D polymorphism with spreading of SARS-CoV2 and highlighted a slip section towards detection and these studies show specificity with older males, high diabetes, and hypertension. To address the raised concern, we report synthesis of unique SnO 2-x N x tpod nanostructure, showing affirmative attachment to both ACE1 and ACE2 efficiently. The attachment is examined in different ratios and studied with μ-Raman spectroscopy. The tpod nanostructure has served with its signature raman signals and used as probe for detection of SARS-CoV2 spike protein (S1). The linearity response for tpod raman signal at 630.4 cm -1 shows R 2 0.9705, comparatively peak 1219.13 cm-1 show R 2 0.9865 and calculated limit of detection of 35 nM., 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: Anesthesiologists require an understanding of their patients' outcomes to evaluate their performance and improve their practice. Traditionally, anesthesiologists had limited information about their surgical outpatients' outcomes due to minimal contact post discharge. Leveraging digital health innovations for analyzing personal and population outcomes may improve perioperative care. BC Children's Hospital's postoperative follow-up registry for outpatient surgeries collects short-term outcomes such as pain, nausea, and vomiting. Yet, these data were previously not available to anesthesiologists., Objective: This quality improvement study aimed to visualize postoperative outcome data to allow anesthesiologists to reflect on their care and compare their performance with their peers., Methods: The postoperative follow-up registry contains nurse-reported postoperative outcomes, including opioid and antiemetic administration in the postanesthetic care unit (PACU), and family-reported outcomes, including pain, nausea, and vomiting, within 24 hours post discharge. Dashboards were iteratively co-designed with 5 anesthesiologists, and a department-wide usability survey gathered anesthesiologists' feedback on the dashboards, allowing further design improvements. A final dashboard version has been deployed, with data updated weekly., Results: The dashboard contains three sections: (1) 24-hour outcomes, (2) PACU outcomes, and (3) a practice profile containing individual anesthesiologist's case mix, grouped by age groups, sex, and surgical service. At the time of evaluation, the dashboard included 24-hour data from 7877 cases collected from September 2020 to February 2023 and PACU data from 8716 cases collected from April 2021 to February 2023. The co-design process and usability evaluation indicated that anesthesiologists preferred simpler designs for data summaries but also required the ability to explore details of specific outcomes and cases if needed. Anesthesiologists considered security and confidentiality to be key features of the design and most deemed the dashboard information useful and potentially beneficial for their practice., Conclusions: We designed and deployed a dynamic, personalized dashboard for anesthesiologists to review their outpatients' short-term postoperative outcomes. This dashboard facilitates personal reflection on individual practice in the context of peer and departmental performance and, hence, the opportunity to evaluate iterative practice changes. Further work is required to establish their effect on improving individual and department performance and patient outcomes., (©Rama Syamala Sreepada, Ai Ching Chang, Nicholas C West, Jonath Sujan, Brendan Lai, Andrew K Poznikoff, Rebecca Munk, Norbert R Froese, James C Chen, Matthias Görges. Originally published in JMIR Perioperative Medicine (http://periop.jmir.org), 19.09.2023.)

The Phase 3 single-arm COMMODORE 3 study (ClinicalTrials.gov, NCT04654468) evaluated efficacy and safety of crovalimab (novel C5 inhibitor) in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria (PNH). COMMODORE 3 enrolled patients from five China centers. Eligible complement inhibitor-naive patients with PNH were ≥12 years old, had lactate dehydrogenase (LDH) ≥2 × upper limit of normal (ULN), and had ≥4 transfusions of packed red blood cells within the prior 12 months. Patients received crovalimab loading doses (one intravenous, four subcutaneous) and subsequent every-4-weeks subcutaneous maintenance doses per weight-based tiered-dosing schedule. Co-primary efficacy endpoints were mean proportion of patients with hemolysis control (LDH ≤1.5 × ULN) from Week (W)5 through W25 and difference in proportion of patients with transfusion avoidance from baseline through W25 versus within 24 weeks of prescreening in patients who had ≥1 crovalimab dose and ≥1 central LDH assessment after first dose. Between March 17 and August 24, 2021, 51 patients (15-58 years old) were enrolled; all received treatment. At primary analysis, both co-primary efficacy endpoints were met. Estimated mean proportion of patients with hemolysis control was 78.7% (95% CI: 67.8-86.6). Difference between proportion of patients with transfusion avoidance from baseline through W25 (51.0%; n = 26) versus within 24 weeks of prescreening (0%) was statistically significant (p < .0001). No adverse events led to treatment discontinuation. One treatment-unrelated death (subdural hematoma following a fall) occurred. In conclusion, crovalimab, with every-4-weeks subcutaneous dosing is efficacious and well tolerated in complement inhibitor-naive patients with PNH., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Polyurethanes and plastics have become ubiquitous in modern society, finding use in a wide variety of applications such as clothing, automobiles, and shoes. While these materials provide numerous benefits to human life, their persistence in the environment has caused ecological imbalances. Therefore, new processes are needed to make these materials more sustainable and re-usable. In 2011, Ludwik Leibler introduced a new class of covalent adaptable network (CAN) polymers called Vitrimers. Vitrimers possess self-repairing properties and are capable of being reprocessed due to dynamic exchange or breaking/recombination of covalent bonds, similar to thermoset materials. This study explores the synthesis of Vitrimers using waste polyurethane or plastics as feedstock. The raw materials were glycolysed to obtain the glycolysate, which was then used as a reagent for the Vitrimers synthesis. The main objective of this study was to achieve the maximum self-repairable rate of the prepared sample. The Taguchi orthogonal analysis was employed to guide the experiments. The optimized experimental conditions for polyurethane glycolysis were determined to be under ethylene glycol and catalyzed by sodium hydroxide at 180°C for 1 h, resulting in the highest hydroxyl concentration in the glycolysate. In the second stage of the experiment, the ratio of hexamethylene diisocyanate (HDI) to solvent was set to 2, HDI trimer to solvent was 2, and PGE/glycolysate was 0.5, with equal amounts of PEG and glycolysate used as the solvent. The reaction was carried out at 80°C for 1 h, achieving a self-repair ability of 47.5% in the prepared sample. The results of this study show that waste polyurethane or plastics can be effectively recycled and transformed into vitrimers with self-repairing properties. The use of glycolysis as a feedstock is a promising method for the sustainable recycling of polyurethane waste. The Taguchi orthogonal analysis is an effective approach for optimizing experimental conditions and improving the reproducibility of the results., 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 © 2023 Lin, Chen-Huang and Chang.)

Background: Opioid prescribing guidelines have significantly decreased overprescribing and post-discharge use after cardiac surgery; however, limited recommendations exist for general thoracic surgery patients, a similarly high-risk population. We examined opioid prescribing and patient-reported use to develop evidence-based, opioid prescribing guidelines after lung cancer resection., Methods: This prospective, statewide, quality improvement study was conducted between January 2020 to March 2021 and included patients undergoing surgical resection of a primary lung cancer across 11 institutions. Patient-reported outcomes at 1-month follow-up were linked with clinical data and Society of Thoracic Surgery (STS) database records to characterize prescribing patterns and post-discharge use. The primary outcome was quantity of opioid used after discharge; secondary outcomes included quantity of opioid prescribed at discharge and patient-reported pain scores. Opioid quantities are reported in number of 5-mg oxycodone tablets (mean ± standard deviation)., Results: Of the 602 patients identified, 429 met inclusion criteria. Questionnaire response rate was 65.0%. At discharge, 83.4% of patients were provided a prescription for opioids of mean size 20.5±13.1 pills, while patients reported using 8.2±13.0 pills after discharge (P<0.001), including 43.7% who used none. Those not taking opioids on the calendar day prior to discharge (32.4%) used fewer pills (4.4±8.1 vs. 11.7±14.9, P<0.001). Refill rate was 21.5% for patients provided a prescription at discharge, while 12.5% of patients not prescribed opioids at discharge required a new prescription before follow-up. Pain scores were 2.4±2.5 for incision site and 3.0±2.8 for overall pain (scale 0-10)., Conclusions: Patient-reported post-discharge opioid use, surgical approach, and in-hospital opioid use before discharge should be used to inform prescribing recommendations after lung resection., 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-22-1621/coif). RMA reports grants and travel expenses when proctoring for Edwards Lifesciences, Intuitive Surgical, and Ethicon – Johnson & Johnson. JR Martin reports consulting fees and webinars for Terumo. CMB reports consulting fees from Heron Therapeutics, Vertex Pharmaceuticals, Benter Foundation, and Alosa Health, as well as receiving payment for providing expert testimony. ACC previously served as the President of the Michigan Society of Thoracic & Cardiovascular Surgeons. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Ribonucleotide reductases (RRs or RNRs) catalyze the reduction of the OH group on the 2nd carbon of ribose, reducing four ribonucleotides (NTPs) to the corresponding deoxyribonucleotides (dNTPs) to promote DNA synthesis. Large DNA viruses, such as herpesviruses and poxviruses, could benefit their replication through increasing dNTPs via expression of viral RRs. Little is known regarding the relationship between cellular RRs and RNA viruses. Mammalian RRs contain two subunits of ribonucleotide reductase M1 polypeptide (RRM1) and two subunits of ribonucleotide reductase M2 polypeptide (RRM2). In this study, expression of cellular RRMs, including RRM1 and RRM2, is found to be down-regulated in hepatitis C virus (HCV)-infected Huh7.5 cells and Huh7 cells with HCV subgenomic RNAs (HCVr). As expected, the NTP/dNTP ratio is elevated in HCVr cells. Compared with that of the control Huh7 cells with sh-scramble, the NTP/dNTP ratio of the RRM-knockdown cells is elevated. Knockdown of RRM1 or RRM2 increases HCV replication in HCV replicon cells. Moreover, inhibitors to RRMs, including Didox, Trimidox and hydroxyurea, enhance HCV replication. Among various HCV viral proteins, the NS5A and/or NS3/4A proteins suppress the expression of RRMs. When these are taken together, the results suggest that HCV down-regulates the expression of RRMs in cultured cells to promote its replication.

The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28 days), ranging from milder (TG1-3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of >15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72 h of hospital admission that distinguish moderate from severe and fatal COVID-19 disease. Importantly, cellular and molecular states also distinguish participants with more severe disease that recover or stabilize within 28 days from those that progress to fatal outcomes (TG4 vs. TG5). Furthermore, our longitudinal design reveals that these biologic states display distinct temporal patterns associated with clinical outcomes. Characterizing host immune responses in relation to heterogeneity in disease course may inform clinical prognosis and opportunities for intervention., Competing Interests: Declaration of interests The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines, which list F.K. as co-inventor. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. F.K. has consulted for Merck and Pfizer (before 2020) and is currently consulting for Pfizer, Seqirus, Third Rock Ventures, Merck, and Avimex. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2. Viviana Simon is a co-inventor on a patent filed relating to SARS-CoV-2 serological assays (the “Serology Assays”). O.L. is a named inventor on patents held by Boston Children’s Hospital relating to vaccine adjuvants and human in vitro platforms that model vaccine action. His laboratory has received research support from GlaxoSmithKline (GSK). C.B.C. serves as a consultant to bioMerieux and is funded for a grant from the Bill & Melinda Gates Foundation. J.A.O. is a consultant at Knocean, Inc. J.L.-S. serves as a scientific advisor of Precion, Inc. S.R.H., G.M., and K.W. are employees of Metabolon, Inc. V.S.-M. is a current employee of MyOwnMed. N.R. reports contracts with Lilly and Sanofi for COVID-19 clinical trials and serves as a consultant for ICON EMMES for consulting on safety for COVID19 clinical trials. A. Rahman is a current employee of Immunai, Inc. S.H.K. is a consultant related to ImmPort data repository for Peraton. N.D.G. is a consultant for Tempus Labs and the National Basketball Association. Akiko Iwasaki is a consultant for 4BIO, Blue Willow Biologics, Revelar Biotherapeutics, RIGImmune, Xanadu Bio, and Paratus Sciences. M. Kraft receives research funds paid to her institution from NIH and ALA and from Sanofi and Astra-Zeneca for work in asthma; serves as a consultant for Astra-Zeneca, Sanofi, Chiesi, and GSK for severe asthma; and is a co-founder and CMO for RaeSedo, Inc., a company created to develop peptidomimetics for treatment of inflammatory lung disease. E. Melamed received research funding from Babson Diagnostics and honorarium from Multiple Sclerosis Association of America and has served on the advisory boards of Genentech, Horizon, Teva, and Viela Bio., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Mitochondrial dysfunction is a hallmark of heart failure. Mitochondrial transplantation has been demonstrated to be able to restore heart function, but its mechanism of action remains unresolved. Using an in-house optimized mitochondrial isolation method, we tested efficacy of mitochondria transplantation in two different heart failure models. First, using a doxorubicin-induced heart failure model, we demonstrate that mitochondrial transplantation before doxorubicin challenge protects cardiac function in vivo and prevents myocardial apoptosis, but contraction improvement relies on the metabolic compatibility between transplanted mitochondria and treated cardiomyocytes. Second, using a mutation-driven dilated cardiomyopathic human induced pluripotent stem cell-derived cardiomyocyte model, we demonstrate that mitochondrial transplantation preferentially boosts contraction in the ventricular myocytes. Last, using single-cell RNA-seq, we show that mitochondria transplantation boosts contractility in dystrophic cardiomyocytes with few transcriptomic alterations. Together, we provide evidence that mitochondria transplantation confers myocardial protection and may serve as a potential therapeutic option for heart failure., Competing Interests: Declaration of interests None., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The role of operative approach in surgical lymphadenectomies and pathologic nodal upstaging for lung cancer remains unclear., Methods: This study retrospectively reviewed patients who underwent lobectomy for non-small cell lung cancer from January 2015 to December 2020 at 16 centers within a statewide quality improvement collaborative in Michigan. Patients were stratified by operative approach, and our primary end points were number of LN recovered, number of LN stations sampled, and rates of nodal upstaging with nodal upstaging defined as a higher final pathologic nodal stage compared with preoperative clinical nodal staging., Results: A total of 3036 patients were included: 608 (20.0%) with open lobectomies, 1362 (41.3%) with video-assisted thoracoscopic surgery (VATS), and 1233 (37.4%) with robot-assisted thoracoscopic surgery (RATS) lobectomies. Using multivariable logistic regression, study investigators found that VATS was associated with lower rates of nodal upstaging (odds ratio [OR], 0.71; 95% CI, 0.54-0.94; P = .015) and harvesting ≥10 LNs (OR, 0.40; 95% CI, 0.31-0.50; P < .001) as compared with open surgery, whereas no significant difference was found between RATS and open techniques. Compared with open surgery, VATS had lower rates of sampling at ≥5 nodal stations (OR, 0.66; 95% CI, 0.53-0.84; P = .001), whereas RATS rates were higher (OR, 2.38; 95% CI, 1.85-3.06; P < .001)., Conclusions: VATS lobectomies were associated with lower rates of harvesting ≥10 LNs, sampling ≥5 LN stations, and pathologic nodal upstaging compared with open and RATS lobectomies. Compared with open procedures, RATS lobectomies were associated with higher rates of sampling ≥5 LN stations, but there was no significant difference between open and RATS approaches in rates of nodal upstaging or harvesting ≥10 LNs., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Lung cancer is an extremely common cancer and metastatic lung cancer has a greatly low survival rate. Lymphangiogenesis is essential for the development and metastasis of lung cancer. The adipokine angiopoietin-like protein 2 (ANGPTL2) regulates tumor progression and metastasis, although the functions of ANGPTL2 in lung cancer are unknown. Analysis of data from TCGA genomics program, the GEPIA web server and the Oncomine database revealed that higher levels of ANGPTL2 expression were correlated with progressive disease and lymph node metastasis. ANGPTL2 enhanced VEGF-A-dependent lymphatic endothelial cell (LEC) tube formation and migration. Integrin α5β1, p38 and nuclear factor (NF)-κB signaling mediated ANGPTL2-regulated lymphangiogenesis. Importantly, overexpression ANGPTL2 facilitated tumor growth and lymphangiogenesis in vivo . Thus, ANGPTL2 is a promising therapeutic object for treating lung cancer.

Cancer-associated fibroblasts (CAFs) were presumed absent in glioblastoma given the lack of brain fibroblasts. Serial trypsinization of glioblastoma specimens yielded cells with CAF morphology and single-cell transcriptomic profiles based on their lack of copy number variations (CNVs) and elevated individual cell CAF probability scores derived from the expression of 9 CAF markers and absence of 5 markers from non-CAF stromal cells sharing features with CAFs. Cells without CNVs and with high CAF probability scores were identified in single-cell RNA-Seq of 12 patient glioblastomas. Pseudotime reconstruction revealed that immature CAFs evolved into subtypes, with mature CAFs expressing actin alpha 2, smooth muscle (ACTA2). Spatial transcriptomics from 16 patient glioblastomas confirmed CAF proximity to mesenchymal glioblastoma stem cells (GSCs), endothelial cells, and M2 macrophages. CAFs were chemotactically attracted to GSCs, and CAFs enriched GSCs. We created a resource of inferred crosstalk by mapping expression of receptors to their cognate ligands, identifying PDGF and TGF-β as mediators of GSC effects on CAFs and osteopontin and HGF as mediators of CAF-induced GSC enrichment. CAFs induced M2 macrophage polarization by producing the extra domain A (EDA) fibronectin variant that binds macrophage TLR4. Supplementing GSC-derived xenografts with CAFs enhanced in vivo tumor growth. These findings are among the first to identify glioblastoma CAFs and their GSC interactions, making them an intriguing target.

Background: Previous studies have identified postoperative complications as being associated with readmission after lobectomy. However, these studies have not adequately accounted for the timing of complications or accounted for institutional effects. Our objectives were to examine readmission rates after lobectomy and identify factors associated with readmission., Methods: Patients aged >18 years undergoing lobectomy for lung cancer between 2015 and 2019 were identified from a statewide database. Patients with in-hospital mortality, missing data regarding discharge status, 30-day readmission status, and discharge location were excluded. Data regarding The Society of Thoracic Surgeons postoperative complications were abstracted by hospital data managers to determine the timing of occurrence (index admission vs readmission). Logistic mixed-model analysis, with hospitals as the random intercept to account for clustering data structure and assess hospital-specific effect on readmission, was performed., Results: The overall readmission rate was 6.9% (184 of 2686). The most common complication was air leak ≥5 days in 17.4% (467 of 2686). Variables significantly predictive of more readmission were predischarge postoperative complications and Zubrod score ≥1. Variables predictive of less readmission were increasing length of stay and having been operated on at institutions with higher cumulative volume or having postdischarge follow-up visit protocol ≤7 days from discharge. The C statistic for the final model was 0.80., Conclusions: Patients who experience postoperative complications are at increased risk for readmission, whereas follow-up ≤7 days was predictive of less risk for readmission. Efforts at reducing readmissions should focus on decreasing postoperative complication rates, the timing of discharge for patients experiencing complications, as well as decreasing length of time between discharge and clinic follow-up., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Metastatic prostate cancer (PCa) predicts a poor prognosis and lower likelihood of survival. Osteoblasts (OBs) are known to be responsible for the synthesis and mineralization of bone, although it is unclear as to whether PCa in the prostate gland cooperates with OBs in bone to promote PCa malignant transformation. We aimed to elucidate how primary PCa cells cooperate with distal OBs and contribute to the vicious cycle that leads to metastatic PCa. Methods: N-cadherin, E-cadherin, and Twist protein expression were measured by Western blot. Twist translocation into the nucleus was detected by the immunofluorescence (IF) assay. Enzyme-linked immunosorbent assay (ELISA) detected protein levels in human serum samples. Levels of candidate protein expression were examined by the human cytokine array. Prostate tumor growth and metastasis were analyzed by orthotopic and metastatic prostate cancer models, respectively. Immunohistochemistry (IHC) staining was used to observe ADAM metallopeptidase domain 9 (ADAM9) and WNT1 inducible signaling pathway protein 1 (WISP-1) expression in tissue. Results: Our in vitro and in vivo analyses have now discovered that primary PCa expressing ADAM9 protein enables the transformation of OBs into PCa-associated osteoblasts (PCa-OBs), inducing WISP-1 secretion from PCa-OBs in the bone microenvironment. The upregulation of WISP-1 in bone provided feedback to primary PCa and promoted PCa cell aggressiveness via epithelial-mesenchymal transition (EMT) activity. Elevated levels of WISP-1 expression were detected in the serum of patients with PCa. ADAM9 levels were overexpressed in tumor tissue from PCa patients; ADAM9 blockade interrupted OB-induced release of WISP-1 and also suppressed primary tumor growth and distal metastasis in orthotopic PCa mouse models. Conclusion: Our study suggests that the ADAM9/WISP-1 axis assists with metastatic PCa progression. Thus, targeting the ADAM9/WISP-1 axis may help to prevent the malignant phenotypes of PCa cells., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The current era of big data offers a wealth of new opportunities for clinicians to leverage artificial intelligence to optimize care for pediatric and adult patients with a congenital heart disease. At present, there is a significant underutilization of artificial intelligence in the clinical setting for the diagnosis, prognosis, and management of congenital heart disease patients. This document is a call to action and will describe the current state of artificial intelligence in congenital heart disease, review challenges, discuss opportunities, and focus on the top priorities of artificial intelligence-based deployment in congenital heart disease., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Introduction: Cigarette smoking is the main risk factor for lung cancer. MSCs in the TME promoting tumor angiogenesis, growth, and metastasis. SIBLING proteins enable cancer cells to extend, invade and metastasize., Objectives: Cigarette smoke promotes the progression and metastasis of lung cancer, although how this occurs is poorly understood. We evaluated the impact of whether cigarette smoking motivates SIBLING protein expression and is involved in MSC-mediated lung tumor metastasis., Methods: We investigated the expression of OPN in the Gene Expression Omnibus (GEO) databases and confirmed the results by immunohistochemistry (IHC), qPCR and Western blotting (WB) of lung cancer cells and tissues. The effect of OPN on the recruitment and adhesion of mesenchymal stem cells (MSCs) to lung cancer cells and lung cancers metastasis was investigated by Transwell, adhesion assays. A series of in vitro and in vivo experiments were conducted to demonstrate the mechanisms by which OPN modulates recruitment and adhesion of MSCs to lung cancer cells and lung cancer metastasis., Results: Cigarette smoke extract (CSE) and benzo[α]pyrene (B[α]P) increased levels of OPN expression and facilitated the recruitment and adhesion of MSCs to lung cancer cells via JAK2/STAT3 signaling. We also observed that OPN promotes tumor-associated MSC (TA-MSC) formation through the OPN receptor (integrins αvβ1, αvβ3, αvβ5 or CD44), inducing lung cancer cell migration and invasion. In an orthotopic mouse model of lung cancer, increases in OPN expression promoted by cigarette smoke upregulated MSC recruitment and facilitated lung cancer metastasis. Knockdown of OPN expression inhibited cigarette smoke-induced lung cancer metastasis in vivo., Conclusion: Cigarette smoke increases OPN expression through the JAK2/STAT3 signaling pathway to attract MSC cell recruitment and promote lung cancer metastasis. Our findings offer important insights into how lung cancer metastasis develops in smokers., (Copyright © 2022. Production and hosting by Elsevier B.V.)

Background: Despite demonstration of its clear benefits relative to open approaches, a video-assisted thoracic surgery technique for pulmonary lobectomy has not been universally adopted. This study aims to overcome potential barriers by establishing the essential components of the operation and determining which steps are most useful for simulation training., Methods: After randomly selecting experienced thoracic surgeons to participate, an initial list of components to a lower lobectomy was distributed. Feedback was provided by the participants, and modifications were made based on anonymous responses in a Delphi process. Components were declared essential once at least 80% of participants came to an agreement. The steps were then rated based on cognitive and technical difficulty followed by listing the components most appropriate for simulation., Results: After 3 rounds of voting 18 components were identified as essential to performance of a video-assisted thoracic surgery for lower lobectomy. The components deemed the most difficult were isolation and division of the basilar and superior segmental branches of the pulmonary artery, isolation and division of the lower lobe bronchus, and dissection of lymphovascular tissue to expose the target bronchus. The steps determined to be most amenable for simulation were isolation and division of the branches of the pulmonary artery, the lower lobe bronchus, and the inferior pulmonary vein., Conclusions: Using a Delphi process a list of essential components for a video-assisted thoracic surgery for lower lobectomy was established. Furthermore 3 components were identified as most appropriate for simulation-based training, providing insights for future simulation development., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Prostate cancer commonly affects the urinary tract of men and metastatic prostate cancer has a very low survival rate. Apelin belongs to the family of adipokines and is associated with cancer development and metastasis. However, the effects of apelin in prostate cancer metastasis is undetermined. Analysis of the database revealed a positive correlation between apelin level with the progression and metastasis of prostate cancer patients. Apelin treatment facilitates cell migration and invasion through inhibiting tissue inhibitor of metalloproteinase 2 (TIMP2) expression. The increasing miR-106a-5p synthesis via c-Src/PI3K/Akt signaling pathway is controlled in apelin-regulated TIMP2 production and cell motility. Importantly, apelin blockade inhibits prostate cancer metastasis in the orthotopic mouse model. Thus, apelin is a promising therapeutic target for curing metastatic prostate cancer.

Glioblastoma multiforme (GBM) is a grade IV, highly malignant brain tumor. Because of the heterogeneity of GBM, a multitarget drug is a rational strategy for GBM treatment. Histone deacetylase inhibitors (HDACis) regulate the expression of numerous genes involved in cell death, apoptosis, and tumorigenesis. We found that the HDAC4/HDAC5 inhibitor LMK235 at 0.5 µM significantly reduced the cell viability and colony formation of patient-derived, temozolomide-resistant GBM P#5 TMZ-R, U-87 MG, and T98G cells. Moreover, LMK235 also significantly increased TUBA acetylation, which is an indicator of HDAC inhibition. Interestingly, LMK235 induced MAP1LC3 robust readout and puncta accumulation but did not enhance PARP1 cleavage or the proportion of annexin V-positive cells, suggesting that LMK235-induced cell death occurred via autophagy activation. Further RNA-seq analysis after LMK235 treatment showed that 597 different expression genes compared to control. After bioinformatic analysis by KEGG and STRING, we focused on 34 genes and validated their mRNA expression by qPCR. Further validation showed that 2 µM LMK235 significantly reduced the mRNA and protein expression of SCNN1A. Cell viability of SCNN1A -silenced cells were reduced, but cells were rescued while treated with an autophagy inhibitor bafilomycin A1. Conclusively, SCNN1A plays a role in LMK235-induced autophagy and cell death in GBM cells.