Women are Underrepresented in Non-small Cell Lung Cancer Clinical Trials: A Systematic Review.

PURPOSE: To perform a systematic review of clinical trials examining non-small cell lung cancer (NSCLC) to better understand the equity afforded to women in the study of lung cancer. METHODS: An electronic search was conducted for all NSCLC clinical trials published between 2010 and 2020 with included words "carcinoma, non-small cell, lung" and "non-small cell lung cancer." Studies from PubMed, Cochrane, and SCOPUS were included and were uploaded into Covidence to assist with systematic review. All articles were screened by two separate individuals and reviewed for location, study type, cancer stage, field of study of the research team, and percentage of females included. Student's t-test was used to compare the means of males and females. RESULTS: Across the 269 studies that met inclusion criteria, fewer females than males were enrolled (38.7% vs. 61.1%; p < 0.0001). Compared with studies from 2010 to 2015, those from 2016 to 2020 had greater representation of females (36.7% vs. 41.4%, p = 0.0091, respectively). Both nonsurgical and surgical studies enrolled fewer female than male patients (38.1% vs. 61.7%, p < 0.0001; 43.1% vs. 57.2%, p = 0.0002, respectively). Clinical trials from the USA had the least difference between sexes with an average of 46.7% females enrolled. Less females compared with males were enrolled in early-stage NSCLC (37.6% female vs. 62.6% male, p < 0.0001) and late-stage NSCLC trials (37.6% female vs. 62.0% male, p < 0.0001). CONCLUSIONS: Despite recent improvement, there continues to be significant underrepresentation of females compared with males in NSCLC clinical trials.

Examination of Firefighting as an Occupational Exposure Criteria for Lung Cancer Screening.

PURPOSE: Firefighting is known to be carcinogenic to humans. However, current lung cancer screening guidelines do not account for occupational exposure. We hypothesize that firefighting is an independent risk factor associated with the development of high-risk lung nodules on low-dose CT (LDCT). METHODS: Members of a firefighter's union underwent LDCT at a single institution between April 2022 and June 2023 within a lung cancer screening program. Results were interpreted by designated chest radiologists and reported using the Lung-RADS scoring system. Demographic and radiographic data were recorded, and summary statistics are reported. RESULTS: 1347 individuals underwent lung cancer screening, with a median age of 51 years (IQR 42-58), including 56 (4.2%) females. Overall, 899 (66.7%) were never smokers, 345 (25.6%) were former smokers, and 103 (7.7%) were current smokers. There were 41 firefighters (3.0%) who had high-risk (Lung-RADS 3 or 4) nodules requiring intervention or surveillance, of which 21 (1.5%) were Lung-RADS 3 and 20 (1.5%) that were Lung-RADS 4. Of the firefighters with high-risk nodules, only 6 (14.6%) were eligible for LDCT based on current screening guidelines. There were 7 high-risk nodules (0.5%) that required procedural intervention, 6 (85.7%) of which were from the non-screening eligible cohort. There were also 20 never-smoking firefighters (57.1%) with high-risk nodules that were non-screening eligible. CONCLUSION: Firefighting, even in the absence of smoking history, may be associated with the development of high-risk lung nodules on LDCT. Carefully selected occupational exposures should be considered in the development of future lung cancer screening guidelines.

Deciphering the role of wound healing genes in skin cutaneous melanoma: Insights into expression, methylation, mutations, and therapeutic implications.

Skin Cutaneous Melanoma (SKCM) is a form of cancer that originates in the pigment-producing cells, known as melanocytes, of the skin. Delay wound healing is often correlated with the occurrence of and progression of SKCM. In this comprehensive study, we investigated the intricate roles of two important wound healing genes in SKCM, including Matrix Metalloproteinase-2 (MMP2) and Matrix Metalloproteinase-9 (MMP9). Through a multi-faceted approach, we collected clinical samples, conducted molecular experiments, including RT-qPCR, bisulphite sequencing, cell culture, cell Counting Kit-8, colony formation, and wound healing assays. Beside this, we also used various other databases/tools/approaches for additional analysis including, UALCAN, GEPIA, HPA, MEXPRESS, cBioPortal, KM plotter, DrugBank, and molecular docking. Our results revealed a significant up-regulation of MMP2 and MMP9 in SKCM tissues compared to normal counterparts. Moreover, promoter methylation analysis suggested an epigenetic regulatory mechanism. Validations using TCGA datasets and immunohistochemistry emphasized the clinical relevance of MMP2 and MMP9 dysregulation. Functional assays demonstrated their synergistic impact on proliferation and migration in SKCM cells. Furthermore, we identified potential therapeutic candidates, Estradiol and Calcitriol, through drug prediction and molecular docking analyses. These compounds exhibited binding affinities, suggesting their potential as MMP2/MMP9 inhibitors. Overall, our study elucidates the diagnostic, prognostic, and therapeutic implications of MMP2 and MMP9 in SKCM, shedding light on their complex interplay in SKCM occurrence and progression.

Perioperative prophylactic corticosteroids for cardiac surgery in children: A systematic review and meta-analysis.

OBJECTIVE: Perioperative corticosteroids have been used for pediatric cardiac surgery for decades, but the underlying evidence is conflicting. We aimed to investigate the efficacy and safety of perioperative prophylactic corticosteroids in pediatric heart surgeries. METHODS: We searched electronic databases until March 2023 to retrieve all randomized controlled trials (RCTs) that administered perioperative prophylactic corticosteroids to children undergoing heart surgery. We used RevMan 5.4 to pool risk ratios (RRs) and mean differences (MDs). RESULTS: A total of 12 RCTs (2,209 patients) were included in our review. Corticosteroids administration was associated with a nonsignificant reduction in all-cause mortality (RR 0.62; 95% CI: 0.37-1.02, I2 = 0%; moderate certainty); however, it was associated with a lower duration of mechanical ventilation (MV) (MD -0.63 days; 95% CI: -1.16 to -0.09 days, I2 = 41%; high certainty). Corticosteroids did not affect the length of ICU and hospital stay but significantly reduced the incidence of postoperative low cardiac output syndrome (LCOS) (RR 0.76; 95% CI: 0.60-0.96, I2 = 0%; moderate certainty) and reoperation (RR 0.37; 95% CI: 0.19-0.74, I2 = 0%; moderate certainty). There was no increase in adverse events except a higher risk of hyperglycemia and postoperative insulin use. CONCLUSIONS: The use of perioperative corticosteroids in pediatric heart surgeries is associated with a trend toward reduced all-cause mortality without attaining statistical significance. Corticosteroids reduced MV duration, and probably decrease the incidence of LCOS, and reoperations. The choice of corticosteroid agent and dose is highly variable and further larger studies may help determine the ideal agent, dose, and patient population for this prophylactic therapy.

Gradual Analytics of Starch-Interacting Proteins Revealed the Involvement of Starch-Phosphorylating Enzymes during Synthesis of Storage Starch in Potato (Solanum tuberosum L.) Tubers.

The complete mechanism behind starch regulation has not been fully characterized. However, significant progress can be achieved through proteomic approaches. In this work, we aimed to characterize the starch-interacting proteins in potato (Solanum tuberosum L. cv. Desiree) tubers under variable circumstances. Starch-interacting proteins were extracted from developing tubers of wild type and transgenic lines containing antisense inhibition of glucan phosphorylases. Further, proteins were separated by SDS-PAGE and characterized through mass spectrometry. Additionally, starch-interacting proteins were analyzed in potato tubers stored at different temperatures. Most of the proteins strongly interacting with the potato starch granules corresponded to proteins involved in starch metabolism. GWD and PWD, two dikinases associated with starch degradation, were consistently found bound to the starch granules. This indicates that their activity is not only restricted to degradation but is also essential during storage starch synthesis. We confirmed the presence of protease inhibitors interacting with the potato starch surface as previously revealed by other authors. Starch interacting protein profiles of transgenic tubers appeared differently from wild type when tubers were stored under different temperatures, indicating a differential expression in response to changing environmental conditions.

Design of a facile, green and efficient graphene oxide-based electrochemical sensor for analysis of acetaminophen drug.

In this study an efficient and environment friendly electrochemical sensor has been designed for the analysis of acetaminophen (APAP) drug. Electrochemical impedance spectroscopy, differential pulse voltammetry and cyclic voltammetric techniques were used to demonstrate the fabricated erGO/GCE sensor performance. Voltammetric assessment of acetaminophen drug was done using bare GC electrode, drop-casted GO/GC electrode and erGO/GCE electrochemical sensor. Proposed sensor was precisely validated for APAP detection by differential pulse voltammetric technique. Subsequently LOD, LOQ, sensitivity and linearity were determined and found to be 7.23 nM, 21.909 nM, 20.14 µA nM-1 cm-2 and 0.0219-2.30 µM, respectively. The diffusion coefficient of APAP was determined by chronoamperometry, and it was found to be 2.24 × 10-5 cm2.s-1. The synthetic and analytical steps were assessed as per the Green Chemistry's 12 Principles giving a 66 score (acceptable) and 93 score (excellent) for the said steps, respectively. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02628-9.

A Serendipitous Outcome of COVID-19: Modifications to ICU Management.

Nosocomial infections are common in intensive care units (ICUs) and often cause increased morbidity and mortality rates in ICU patients. With the emergence of the highly infectious COVID-19, the high prevalence of hospital-acquired infections (HAIs) in ICU has caused much more concern because patients admitted to the ICU have a more severe and prolonged form of the disease. These patients are more likely to develop HAIs than non-ICU patients. Medical communities adopted several measures to make ICU management safer during the pandemic all over the world. In this study, we re-examined the challenges faced and the changes made in ICU management during the pandemic to speculate how these changes will be relevant post-pandemic and can be permanently incorporated into the ICU to improve safety, management, and critical care and make critical care better equipped for future disease breakouts.

Silencing of Curlin Protein via M13 Phagemid-Mediated Synthetic sRNA Expression Reduces Virulence in the Avian Pathogenic E. coli (APEC).

Curli fimbriae, a virulent factor of the Avian Pathogenic Escherichia coli (APEC), is responsible for adhesion, biofilm formation, and colonization of pathogen. Major curli fimbriae protein is encoded by csgA gene. APEC is one of the leading causes of colibacillosis in poultry flocks and due to excessive use of antibiotics and vaccines in poultry, the emergence of various multi-drug resistant (MDR) bacterial strainsare is frequently reported. The growing concern of MDR bacterial strains necessitate novel antibacterial approaches to combat colibacillosis in poultry. RNA-based gene silencing is a very specific and robust strategy to target specific bacterial factors involved in pathogenicity and virulence. In this study, a phagemid-mediated sRNA expression system to target a vital gene, csgA, is employed. This comprises an M13 phagemid harboring a sRNA expression cassette and a pre-designed GUIDE sequences for the csgA target gene. To target the csgA gene at the mRNA level, a GUIDE sequence was computationally designed for pre-designed sRNA expression cassette. Online web tools were used to predict the binding energy, secondary structure, and off-target binding potential of the sRNA to optimize its expression. Results showed that the designed sRNA has a binding energy of - 29.60 kcal/mol with zero off-targets. After expression of the sRNA in the APEC cells, Ì´ 45% reduction in the csgA level was observed via RT-PCR in the CS-APEC-O1 strains compared to the wt-APEC-O1. Similarly, the biofilm forming ability decreased by 40% in the CS-APEC-O1 strains. The swarming motility and hemagglutination efficiency were not affected by the sRNA expression. Future studies investigating the in vivo efficiency of M13 phagemid delivery are required to evaluate its candidacy in phage therapy.

Comparison of in-vivo failure of single-thread and dual-thread temporary anchorage devices over 18 months: A split-mouth randomized controlled trial.

INTRODUCTION: The purpose of this study was to compare the in-vivo failure rates of single-thread and dual-thread temporary anchorage device (TAD) designs over 18 months. METHODS: Thirty patients with skeletal Class II Division 1 malocclusion requiring anchorage from TADs for retraction of maxillary incisors into the extracted premolar space were recruited in this parallel group, split-mouth, randomized controlled trial. A block randomization sequence was generated with Random Allocation Software (version 2.0; Isfahan, Iran) with the allocations concealed in sequentially numbered, opaque, sealed envelopes. A total of 60 TADs (diameter, 2 mm; length, 10 mm) were placed in the maxillary arches of these patients with random allocation of the 2 types to the left and the right sides in a 1:1 ratio. All TADs were placed between the roots of the second premolar and the first molar and were immediately loaded. Patients were followed for a minimum of 12 months and a maximum of 18 months for the failure of the TADs. Data were analyzed blindly on an intention-to-treat basis. RESULTS: Four TADs (13.3%) failed in the single-thread group, and 6 TADs (20%) failed in the dual-thread group. The McNemar test showed an insignificant difference (P = 0.72) between the 2 groups. An odds ratio of 1.6 (95% confidence interval, 0.39-6.97) showed no significant associations among the variables. Most TADs failed in the first month after insertion (50%). CONCLUSIONS: The failure rate of dual-thread TADs compared with single-thread TADs is statistically insignificant when placed in the maxilla for retraction of the anterior segment. Registration: The trial was not registered before commencement. PROTOCOL: The protocol was not published before the trial.

Pericardioesophageal fistulae after left atrial ablation: a case series.

Pericardioesophageal fistula is an uncommon, yet serious complication that can occur after left atrial ablation for cardiac arrhythmias. Timing of this complication is variable; however, it has been reported to occur from a week to over a month post-ablation. The incidence of this complication after ablation is <0.05%; however with increasing rates of left atrial ablations, early recognition is imperative. Nonspecific symptoms, including chest pain, dysphagia, and fever, can indicate the presence of a fistula within the first month after ablation. Early drainage with subsequent definitive treatment is key to limiting morbidity. Here we report four cases of pericardioesophageal fistula all occurring ~1 month post-ablation, with two patients surviving after prompt diagnosis and surgical treatment. Successful treatment in these two cases was achieved with fistula takedown and intercostal muscle flap interposition and esophageal stenting.

Microlearning Environment of Orthodontic Postgraduate Training Programmes in Pakistan: A Multicentre Cross-Sectional Study.

OBJECTIVE: To explore the perception of residents regarding the microlearning environment of orthodontic postgraduate training programmes across Pakistan. STUDY DESIGN: Descriptive, cross-sectional, multicentre study. Place and Duration of the Study: Department of Orthodontics, Dental College, HITEC Institute of Medical Sciences, Taxila, from February to July 2022. METHODOLOGY: This questionnaire-based study was conducted using a pre-validated HEMLEM tool for data collection. QuestionPro survey tool was utilised for data collection and SPSS version 23 was used for data analysis. Independent t-test and one-way ANOVA were performed for comparison of different subgroups. RESULTS: A total of 204 residents participated in this study and collectively showed a mean score of 45.2. Male residents showed significantly higher level of satisfaction than females. Residents below the age of 25 years and those in the first year of training showed maximum level of satisfaction with their learning environments. In general, participants perceived the teaching quality and supervision as more satisfactory than the staff attitude and behaviour. CONCLUSION: Overall, a higher HEMLEM score was recorded, which suggested that Pakistani orthodontic residents felt satisfied with their microlearning environment. Clinical supervisors, curriculum designers, and programme directors could use the findings of this study to further improve the learning environment of their training programmes. KEY WORDS: Learning environment, Microlearning environment, Residents, Clinical training, Supervision, Staff support.

Minimally Invasive Pneumonectomy vs Open Pneumonectomy: Outcomes and Predictors of Conversion.

BACKGROUND: In the modern era, whether minimally invasive pneumonectomy for non-small cell lung cancer (NSCLC) provides a survival advantage over open pneumonectomy is unknown. METHODS: Patients who underwent pneumonectomy for NSCLC between 2015 and 2020 were queried from the National Cancer Database. Surgical approach was categorized as robot-assisted thoracoscopic surgery (RATS), video-assisted thoracoscopic surgery (VATS), or open pneumonectomy on an intention-to-treat basis. Propensity score matching was performed to balance patient cohorts. Univariate and multivariate regression analyses were used to examine the association between surgical approach and 30- and 90-day mortality, and a Cox proportional hazards model was used to assess overall survival. RESULTS: We identified 3784 patients, including 73% open (n = 2776), 19% VATS (n = 725), and 8% RATS (n = 283). The overall conversion rate from minimally invasive to open was 29.5% (n = 298). After propensity matching 212 patients per cohort, there were no differences between open, VATS, and RATS 30-day (9.4% vs 8.5% vs 7.5%, respectively; P = .807) or 90-day mortality (14.2% vs 12.3% vs 10.4%, respectively; P = .516). Median overall survival was similar among open (48 months; 95% CI, 35.6-64.1 months), VATS (51.0 months; 95% CI, 34.9-72.3 months), and RATS approaches (50 months; 95% CI, 42.6-NA months; P = .560). Multivariate analysis of the matched cohort found no association between approach and overall survival. RATS (odds ratio, 0.67; 95% CI, 0.47-0.94; P = .020) and neoadjuvant chemotherapy (odds ratio, 0.52, 95% CI, 0.27-0.98; P = .045) were found to be protective against conversion to open. CONCLUSIONS: Minimally invasive pneumonectomy can be performed with short-term and long-term survival that are equivalent to open pneumonectomy.

AI4Work Project: Human-Centric Digital Twin Approaches to Trustworthy AI and Robotics for Improved Working Conditions in Healthcare and Education Sectors.

AI and robotics aim to transform workplace landscapes in a several sectors such as manufacturing, logistics, healthcare, construction, agriculture, and education. Central to this evolution is the innovative use of Digital Twin technology, which creates real-time updated virtual replicas of physical systems and entities. This technology is especially transformative in healthcare and education, promising customized and efficient experiences for all involved. This paper outlines the AI4Work project's approach to leveraging Digital Twin Technology to improve work environments in these sectors. The goal of AI4Work is to formulate a workplace where AI and robots seamlessly collaborate with humans, while explores how to best share tasks between humans and machines in six different domains. For healthcare, AI4Work will explore how Digital Twin technology can assist occupational doctors and psychologists in monitoring the physical and mental health of hospital personnel in order to predict burnout symptoms and to create a sustainable working environment. In education, AI4Work will investigate how to uphold the mental health of both educators and students while fostering a more supportive and enduring educational setting.

Minimally invasive vs. conventional mitral valve surgery: a meta-analysis of randomised controlled trials.

Objective: The evidence underlying the efficacy and safety of minimally invasive mitral valve surgery (MIMVS) is inconclusive. We conducted a meta-analysis to evaluate whether MIMVS improves clinical outcomes compared with conventional sternotomy. Methods: We searched MEDLINE (via PubMed), Embase, the Cochrane Library, and ClinicalTrials.gov from inception to January 2024 for all randomised controlled trials (RCTs), comparing MIMVS with conventional mitral valve surgery. RevMan 5.4 was used to analyse the data with risk ratio (RR) and mean difference (MD) as the effect measures. Results: Eight studies reporting data on 7 RCTs were included in our review. There was no significant difference in all-cause mortality, the number of patients requiring blood product transfusion, and the change from baseline in the SF-36 physical function scores between the MIMVS and conventional sternotomy groups. MIMVS reduced the length of hospital stay (MD -2.02 days, 95% CI: -3.66, -0.39) but did not affect the length of ICU stay, re-operation for bleeding, and the incidence of renal injury, wound infection, neurological events, and postoperative moderate or severe mitral regurgitation. MIMVS was associated with a trend toward lower postoperative pain scores (MD -1.06; 95% CI: -3.96 to 0.75). Conclusions: MIMVS reduced the number of days spent in the hospital and showed a trend toward lower postoperative pain scores, but it did not decrease the risk of all-cause mortality or the number of patients needing blood product transfusions. Further large-scale RCTs are required to inform definitive conclusions, particularly with regard to quality-of-life outcomes investigating functional recovery. Systematic Review Registration: PROSPERO (CRD42023482122).

Non-alcoholic fatty liver disease among visitors to a hepatitis awareness programme.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide. The present study aimed to evaluate the prevalence of NAFLD among the visitors screened on World Hepatitis Day 2010 and 2011. METHODS: Attendees of the hepatitis awareness programme (n = 928) were offered screening to rule out liver ailments. The participants were evaluated on history, body mass index (BMI) measurement, blood tests for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (anti-HCV), alanine aminotransferase (ALT) levels and abdominal ultrasound (US). RESULTS: On ultrasonography, fatty liver was present in 142 of 806 subjects who were found negative for viral serology and had no history of regular alcohol intake. This accounted for 15.3% of all the visitors. Comparing them with the rest of the serology-negative alcohol-negative subjects, there were more housewives (p = 0.005) with fatty liver. They were older with mean age 43.3 +/- 12.1 years compared to 33.1 +/- 16.1 years (p = 0.000) in patients without fatty liver and had a higher BMI 28.6 +/- 6.0 kg/m2 vs. 22.2 +/- 5.3 kg/m2 (p = 0.000). Regression analysis suggested BMI as the only significant independent risk factor (p = 0.000). However, 32 subjects with fatty liver had BMI < 25 kg/m2 and 6 of them had diabetes mellitus. Thirty-one subjects (21.8%) with fatty liver had raised ALT level (p = 0.000) and possible non-alcoholic steatohepatitis (NASH) which accounts for 3.34% (31/928) of the total visitors. CONCLUSIONS: This analysis reveals that our general population is at risk of having NAFLD and NASH and these should be looked into even in non-obese persons.

Toward Sustainable Healthcare Systems: A Low and Middle-Income Country's Case for Investing in Healthcare Reforms.

Pakistan, a low and middle-income country (LMIC), faces challenges in providing sustainable health care to its population due to inadequate financing, weak healthcare infrastructure, and insufficient health human resources. These challenges are not unique to Pakistan and are faced by many LMICs globally. In this paper, we aim to identify key strategies for achieving sustainable healthcare systems in Pakistan and to draw lessons for LMICs globally, keeping in view the healthcare reforms in Pakistan. We conducted a comprehensive literature review of existing policies and practices related to healthcare financing, service delivery, health information and communication technologies (ICTs), governance and leadership, and health human resources in Pakistan and other LMICs. We also reviewed relevant global policies and frameworks, including the Sustainable Development Goals (SDGs) and the World Health Organization's (WHO) health system strengthening guidelines. To achieve sustainable healthcare systems in Pakistan, we recommend comprehensive healthcare financing policies, including increasing budgetary allocations for health, social health protection through universal coverage, and supporting health and economic development processes. Service delivery can be improved through restructuring public health facilities, incorporating behavioral and social health determinants into primary health care, aligning healthcare delivery with the community, and promoting collaborative leadership between the public and private sectors. The use of ICT can be expanded by implementing e-health policies, disseminating authentic public health information, and enabling telemedicine services. Effective healthcare governance and leadership can be promoted through meritorious, transparent, and accountable reforms, stable healthcare structures at all community levels, and appropriate health policy and organizational frameworks. Finally, strengthening health human resources can be achieved through compliant policy implementation and revisions in laws and policies governing medical teaching institutions. Achieving sustainable healthcare systems in Pakistan and LMICs globally requires comprehensive strategies for healthcare financing, service delivery, health ICT, governance and leadership, and health human resources. By drawing on global policies and frameworks and lessons from other LMICs, Pakistan can overcome its healthcare challenges and contribute to the achievement of the SDGs.