Cardiopulmonary exercise variables and their association with postoperative morbidity and mortality after major oesophagogastric cancer surgery-a multicentre observational study.

Background: Outcomes after oesophagogastric cancer surgery remain poor. Cardiopulmonary exercise testing (CPET) used for risk stratification before oesophagogastric cancer surgery is based on conflicting evidence. This study explores the relationship between CPET and postoperative outcomes, specifically for patients undergoing neoadjuvant treatment. Methods: Patients undergoing oesophagogastric cancer resection and CPET (pre- or post-neoadjuvant treatment, or both) were retrospectively enrolled into a multicentre pooled cohort study. Oxygen uptake at peak exercise (VO2 peak) was compared with 1-yr postoperative survival. Secondary analyses explored relationships between patient characteristics, tumour pathology characteristics, CPET variables (absolute, relative to weight, ideal body weight, and body surface area), and postoperative outcomes (morbidity, 1-yr and 3-yr survival) were assessed using logistic regression analyses. Results: Seven UK centres recruited 611 patients completing a 3-yr postoperative follow-up period. Oesophagectomy was undertaken in 475 patients (78%). Major complications occurred in 25%, with 18% 1-yr and 43% 3-yr mortality. No association between VO2 peak or other selected CPET variables and 1-yr survival was observed in the overall cohort. In the overall cohort, the anaerobic threshold relative to ideal body weight was associated with 3-yr survival (P=0.013). Tumour characteristics (ypT/ypN/tumour regression/lymphovascular invasion/resection margin; P<0.001) and Clavien-Dindo ≥3a (P<0.001) were associated with 1-yr and 3-yr survival. On subgroup analyses, pre-neoadjuvant treatment CPET; anaerobic threshold (absolute; P=0.024, relative to ideal body weight; P=0.001, body surface area; P=0.009) and VE/VCO2 at anaerobic threshold (P=0.026) were associated with 3-yr survival. No other CPET variables (pre- or post-neoadjuvant treatment) were associated with survival. Conclusions: VO2 peak was not associated with 1-yr survival after oesophagogastric cancer resection. Tumour characteristics and major complications were associated with survival; however, only some selected pre-neoadjuvant treatment CPET variables were associated with 3-yr survival. CPET in this cohort of patients demonstrates limited outcome predictive precision. Clinical trial registration: NCT03637647.

Precision enhancement in variance estimation for complex environmental populations using adaptive cluster sampling.

Estimating dispersion in populations that are extremely rare, hidden, geographically clustered, and hard to access is a well-known challenge. Conventional sampling approaches tend to overestimate the variance, even though it should be genuinely reduced. In this environment, adaptive cluster sampling is considered to be the most efficient sampling technique as it provides generally a lower variance than the other conventional probability sampling designs for the assessment of rare and geographically gathered population parameters like mean, total, variance, etc. The use of auxiliary data is very common to obtain the precise estimates of the estimators by taking advantage of the correlation between the survey variable and the auxiliary data. In this article, we introduced a generalized estimator for estimating the variance of populations that are rare, hidden, geographically clustered and hard-to-reached. The proposed estimator leverages both actual and transformed auxiliary data through adaptive cluster sampling. The expressions of approximate bias and mean square error of the proposed estimator are derived up to the first-order approximation using Taylor expansion. Some special cases are also obtained using the known parameters associated with the auxiliary variable. The proposed class of estimators is compared with available estimators using simulation and real data applications.

Exploring the experiences of content experts with item vetting during item bank development.

Objective: To explore content experts' experiences with item vetting during item bank development at a public sector medical university of Rawalpindi, Pakistan. Methods: An exploratory study was carried out from December 2022 to February 2023 at a public sector medical college of Rawalpindi. A purposive sampling technique was employed to collect data from all content experts of the study institute who participated in item vetting activity during pre-exam moderation in the university. A pilot-tested semi-structured interview guide was utilized, interviews were audio recorded and later transcribed. Participants' anonymity was ensured. Various quality assurance strategies were employed to ensure the trustworthiness of the findings. Thematic analysis was performed on the transcribed data and themes were finalized by achieving consensus among all authors. Results: Six themes overarching the fourteen subthemes emerged from the data. Participants expressed a profound sense of satisfaction and valued their experience in refining expertise in constructing multiple-choice questions (MCQs). It was widely acknowledged that such activities not only contribute to the enhancement of item development skills but also improve quality of items. Conclusions: The consistent implementation of item vetting routines, in conjunction with diligent adherence to item writing protocols, contributes to quality assurance measures in assessment. Item bank development for fair and transparent assessment ensures production of competent healthcare professionals filtering incompetent ones hence improving health care services in the community.

Ocrelizumab-induced organizing pneumonia in multiple sclerosis: case report and literature review.

Patients with relapsing-remitting multiple sclerosis should be offered disease-modifying therapies as part of their management. Recommended options include integrin antagonist therapy including natalizumab as well as anti-CD20 monoclonal antibodies like, ocrelizumab, rituximab, ofatumumab, and ublituximab. These therapies reduce relapse rates and slow brain lesion accumulation. Disease-modifying therapies selection may depend on patient preferences, potential fetal harm, and specific drug risks, requiring continuous monitoring via tracking clinical relapses and new MRI brain lesions. Natalizumab carries a risk of progressive multifocal leukoencephalopathy, particularly in anti-JCV antibody-positive patients, necessitating regular monitoring. Ocrelizumab, rituximab, and ublituximab are associated with an increased risk of infections (especially respiratory and skin infections), infusion reactions, and hypogammaglobulinemia. Ocrelizumab additionally poses a heightened risk of immune-mediated colitis and breast cancer, and it is contraindicated for patients with active hepatitis B due to the risk of viral reactivation. Ublituximab has been noted to be linked to potential fetal harm. We report the case of a 42-year-old male with relapsing-remitting multiple sclerosis on ocrelizumab who developed persistent fever and shortness of breath, two weeks after his last ocrelizumab dose. Despite antibiotic treatment for suspected pneumonia, his symptoms persisted. A chest CT scan revealed multifocal ground-glass opacities suggestive of organizing pneumonia, likely secondary to ocrelizumab. The patient's condition improved with high-dose corticosteroids, underscoring the importance of vigilance for extremely rare ocrelizumab-associated pulmonary side effects and the need for prompt, appropriate intervention.

Comparison of efficacy and safety of tofacitinib and azathioprine in patients with alopecia areata and variants: a double-blind, randomized controlled trial.

BACKGROUND: Alopecia areata (AA) is an autoimmune pathology manifested by loss of hair. OBJECTIVE: To evaluate and compare the efficacy and safety of tofacitinib and azathioprine in patients with AA and variants. METHODS: In this double-blind randomized controlled trail (RCT) carried out at the Department of Dermatology, Medical Teaching Institute-Lady Reading Hospital (MTI-LRH), Peshawar, Pakistan, patients aged ≥ 12 years diagnosed with AA, alopecia totalis (AT) or alopecia universalis (AU) with minimum 50% scalp hair loss for a period ≥ 06 years were included. Patients were randomly assigned to receive oral tofacitinib 5 mg twice daily (Group I) or oral azathioprine 2 mg/kg body weight once daily (Group II). The primary endpoint was Severity of Alopecia Tool (SALT) score, evaluated at baseline and 06 months follow-up. Safety was consistently assessed during the study. RESULTS: A total of 104 patients underwent random allocation into either the tofacitinib group (n = 52) or the azathioprine group (n = 52). The mean (SD) age of patients was 20.23 (7.14) years and 22.26 (8.07) years, while the mean (SD) disease duration was 6.59 (4.01) years and 7.98 (4.40) years in in Group I and II, respectively. Overall, 40 (38.5%) patients were adolescents while 70 (67.3%) were male. 52 (50%) had AA, 37 (35.5%) had AT and 15 (14.5%) had AU. Mean baseline SALT score in tofacitinib group was 91.02 ± 10.21 and azathioprine group was 91.02 ± 10.63, which at 06 months follow-up improved to 14.1 ± 24.6 and 63.9 ± 33.9, respectively (difference, 11.5 points; 95% confidence interval, 38.3-61.3, p < 0.0001). Overall, no major adverse effects and no difference among the minor adverse effects in the two groups (04 adverse events for tofacitinib group and 08 for azathioprine group: p = 0.23) was observed. CONCLUSIONS: Efficacy of tofacitinib was significantly higher than azathioprine, whilst both drugs were well-tolerated in patients with AA and variants.

Awake neurosurgery: Advancements in microvascular decompression for trigeminal neuralgia.

Background: The treatment landscape for trigeminal neuralgia (TN) involves various surgical interventions, among which microvascular decompression (MVD) stands out as highly effective. While MVD offers significant benefits, its success relies on precise surgical techniques and patient selection. In addition, the emergence of awake surgery techniques presents new opportunities to improve outcomes and minimize complications associated with MVD for TN. Methods: A thorough review of the literature was conducted to explore the effectiveness and challenges of MVD for TN, as well as the impact of awake surgery on its outcomes. PubMed and Medline databases were searched from inception to March 2024 using specific keywords "Awake Neurosurgery," "Microvascular Decompression," AND "Trigeminal Neuralgia." Studies reporting original research on human subjects or preclinical investigations were included in the study. Results: This review highlighted that MVD emerges as a highly effective treatment for TN, offering long-term pain relief with relatively low rates of recurrence and complications. Awake surgery techniques, including awake craniotomy, have revolutionized the approach to MVD, providing benefits such as reduced postoperative monitoring, shorter hospital stays, and improved neurological outcomes. Furthermore, awake MVD procedures offer opportunities for precise mapping and preservation of critical brain functions, enhancing surgical precision and patient outcomes. Conclusion: The integration of awake surgery techniques, particularly awake MVD, represents a significant advancement in the treatment of TN. Future research should focus on refining awake surgery techniques and exploring new approaches to optimize outcomes in MVD for TN.

Impact of Drain Placement on Postoperative Complications after Thyroidectomy for Substernal Goiter.

Introduction Despite the evidence against drain placement after thyroidectomy, there is a lack of consensus on drain use in patients with substernal goiter. Objective To assess the factors that increase the likelihood of drain placement and its impact on postoperative hematoma and other 30-day complications among adult patients undergoing thyroidectomy for substernal goiter. Methods A retrospective cohort study that used data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Adult patients (aged ≥ 18 years) who underwent elective thyroidectomy for substernal goiter from 2016 to 2020 were included. Cases with closed suction neck drains placed upon completion of surgery were included in the drain group, and the remaining cases formed the nondrain group. Results A total of 1,229 patients were included (46.5% with drain placement). The factors that increased the likelihood of drain placement included body mass index (BMI) ≥ 30 kg/m 2 , score between 3 and 5 on the American Society of Anesthesiologists (ASA) physical status classification, sternal split/transthoracic surgical approach, operative time ≥ 90 minutes, and surgery conducted by otolaryngologists. Patients with clean-contaminated or contaminated wound classifications were less likely to be submitted to drain placement. In addition, drain use had no impact on postoperative hematoma formation but was found to independently increase the risk of prolonged length of hospital stay. Conclusion Thyroidectomy without drain placement might be safe for substernal goiter. However, this decision should be individualized for each patient. Level Of Evidence: 3.

Fibrillary Glomerulonephritis Leading to End-Stage Renal Disease in the Absence of Active or Chronic Hepatitis C Infection: Current Insights.

Fibrillary glomerulonephritis (FGN) is a rare glomerular disease with various etiologies, including idiopathic cases and associations with autoimmune diseases, neoplasms, and viral infections, such as Hepatitis C. We present a case of a patient who developed acute kidney injury (AKI) with atypical clinical features. A subsequent renal biopsy confirmed the diagnosis of FGN, with distinct immunofluorescence staining for DNAJB9. The patient tested positive for Hepatitis C antibodies with an undetectable viral load, indicating a past infection that had self-cleared. This finding prompted further investigation of the association between Hepatitis C and the development of FGN.

Enhancing water stress tolerance of bread wheat during seed germination and seedling emergence: caffeine-induced modulation of antioxidative defense mechanisms.

Better crop stand establishment, a function of rapid and uniform seedling emergence, depends on the activities of germination-related enzymes, which is problematic when there is insufficient soil moisture. Different ways are in practice for counteracting this problem, including seed priming with different chemicals, which are considered helpful in obtaining better crop stand establishment to some extent through improved seed germination and seedling emergence. In this growth room experiment, caffeine was used as a seed priming agent to improve germination under moisture scarcity. Polyethylene glycol-8000 (18%) was added to Hoagland's nutrient solution to create drought stress (-0.65 MPa). The experiment was arranged in a completely randomized design (CRD), having four replications of each treatment. A newly developed wheat genotype SB-1 was used for the experimentation. Different doses of caffeine, i.e., 4 ppm, 8 ppm, 12 ppm, and 16 ppm, including no soaking and water soaking, were used as seed priming treatments. Water deficit caused oxidative stress and adversely affected the seed germination, seedling vigor, activities of germination enzymes, photosynthetic pigments, and antioxidative defense mechanism in roots and shoots of seedlings. Caffeine seed priming ameliorated the negative effects of water deficit on seed germination and seedling vigor, which was attributed to the reduction in lipid peroxidation and improvement in the activities of germination-related enzymes like glucosidase, amylase, and protease. Conclusively, seed priming with 12 ppm caffeine outperformed the other treatments and hence is recommended for better crop stand establishment under conditions of soil moisture deficit.

Therapeutic potential of boswellic acids: an update patent review (2016-2023).

INTRODUCTION: Boswellic acids (BAs) are a group of pentacyclic triterpenoids of the ursane and oleanane type. They have shown very interesting biological properties that have led to the development of a number of synthesis protocols. Both natural BAs and their synthetic derivatives may be useful in the treatment of a variety of cancers, viral infections and inflammatory diseases. AREAS COVERED: This review covers patents relating to the therapeutic activities of natural BAs and their synthetic derivatives. The latest patented studies of boswellic acids (are summarized by using the keywords 'boswellic acid,' in SciFinder, PubMed, and Google Patents and databases in the year from 2016 to 2023. EXPERT OPINION: Boswellic acids have shown potent antiviral, anticancer and anti-inflammatory potential. Few BAs analogues have been prepared by modification at the C24-CO2H functional groups. In particular, the C-24 amide and amino analogues have shown enhanced anticancer effects compared to the parent AKBA. In addition, BAs have the ability to form conjugates with other antiviral, anti-inflammatory and anticancer drugs that synergistically enhance their biological efficacy. In addition, this conjugation strategy will increase the solubility and bioavailability of BAs, which is one of the most important issues in the development of BAs.

A review on molecular scissoring with CRISPR/Cas9 genome editing technology.

Genome editing is a technology to make specific changes in the DNA of a cell or an organism. It has significantly altered the landscape of life sciences, facilitating the establishment of exceedingly customized genetic modifications. Among various genome editing technologies, the CRISPR/Cas9 system, a specific endonuclease induces a double stranded DNA break and enabling modifications to the genome, has surfaced as a formidable and adaptable instrument. Its significance cannot be overstated, as it not only allows for the manipulation of genomes in model organisms but also holds great potential for revolutionary advances in medicine, particularly in treating genetic diseases. This review paper explores the remarkable journey of CRISPR/Cas9, its natural function, mechanisms, and transformative impact on genome editing and finally the use of artificial intelligence and other intelligent manufacturing tools used. The introduction provides the background on genome editing, emphasizing the emergence and significance of CRISPR/Cas9. Subsequent sections comprehensively elucidate its natural function, disease modeling, agriculture, and biotechnology, address therapeutic applications, and ongoing clinical trials while also discussing prospects and ethical implications. We summarized the key findings, indicating that CRISPR/Cas9 has empowered the creation of disease-specific animal models. This provides invaluable insights into pathogenic mechanisms and opens new avenues for drug discovery, reaffirming the transformative impact of CRISPR/Cas9 on genome editing. Finally we discussed the importance of continued research and collaboration for comprehensive utilization of the inherent capabilities of this molecular precision tool in shaping forthcoming advancements.

Odor and taste characteristics, transduction mechanism, and perceptual interaction in fermented foods: a review.

Fermentation is a critical technological process for flavor development in fermented foods. The combination of odor and taste, known as flavor, is crucial in enhancing people's perception and psychology toward fermented foods, thereby increasing their acceptance among consumers. This review summarized the determination and key flavor compound screening methods in fermented foods and analyzed the flavor perception, perceptual interactions, and evaluation methods. The flavor compounds in fermented foods could be separated, purified, and identified by instrument techniques, and a molecular sensory science approach could identify the key flavor compounds. How flavor compounds bind to their respective receptors determines flavor perception, which is influenced by their perceptual interactions, including odor-odor, taste-taste, and odor-taste. Evaluation methods of flavor perception mainly include human sensory evaluation, electronic sensors and biosensors, and neuroimaging techniques. Among them, the biosensor-based evaluation methods could facilitate the investigation of the flavor transduction mechanism and the neuroimaging technique could explain the brain's signals that relate to the perception of flavor and how they compare to signals from other senses. This review aims to elucidate the flavor profile of fermented foods and highlight the significance of comprehending the interactions between various flavor compounds, thus improving the healthiness and sensory attributes.

Electrochemical Properties of Mo4VC4Tx MXene in Aqueous Electrolytes.

M5C4Tx MXenes represent the most recently discovered and least studied subfamily of out-of-plane ordered double transition metal carbides with 11 atomic layers, probably the thickest of all 2D materials. Molybdenum (Mo) and vanadium (V) in Mo4VC4Tx offer multiple oxidation states, making this MXene potentially attractive for electrochemical energy storage applications. Herein, we evaluated the electrochemical properties of Mo4VC4Tx free-standing thin films in acidic, basic, and neutral aqueous electrolytes and observed the highest gravimetric capacitance of 219 F g-1 at 2 mV s-1 in a 3 M H2SO4. Further, we investigated the intercalation states of four different cations (H+, Li+, Na+, and K+) in MXenes through ab initio molecular dynamics (AIMD) simulation and used density functional theory (DFT) calculations to assess the charge storage mechanisms in different electrolytes. These studies show hydrated Li+, Na+, and K+ ions forming an electric double layer (EDL) at the MXene surface as the primary charge storage mechanism. This work shows the promise of Mo4VC4Tx MXene for energy storage in aqueous electrolytes.

RAGE signalling contributes to oxidative stress and inflammation in knee osteoarthritis patients with metabolic syndrome.

OBJECTIVES: Metabolic factors play significant role in the natural history of knee osteoarthritis (KO). There is a limited understanding of molecular and cellular events that give rise to the disease in patients. This study explored the possible cellular mechanisms by which metabolic syndrome leads to KO. METHODS: This cross-sectional study enrolled 80 subjects with KO who fulfilled the ACR diagnostic criteria and were undergoing total knee replacement surgery. The patients were divided into two groups: KO patients without metabolic syndrome and KO patients with metabolic syndrome. RESULTS: We hypothesised that metabolic syndrome may accelerate pathogenesis of OA by enhanced RAGE axis in articular cartilage and Infrapatellar fat pad of the knee joint. We have found enhanced protein expression of receptor for advanced glycation end products (RAGE) and its ligands AGEs and HMGB-1 in knee joint tissue of KO patients with metabolic syndrome as compared to KO patients without metabolic syndrome. Further downstream, the gene expression of oxidative stress regulators such as NADPH and inflammation, NFĸB were upregulated in KO patients with MetS as compared to KO patients alone. Higher levels of advanced oxidation products and inflammatory marker IL-17 were exhibited in synovial fluid of KO patients with metabolic syndrome. The enhanced levels of these oxidative stress and inflammatory markers were reflected in the serum of KO patients with metabolic syndrome as well. CONCLUSIONS: We conclude that enhanced function of RAGE axis could be one of the mechanisms by which metabolic syndrome leads to KO.

Prevalence of Cardiovascular Disease (CAD) due to industrial air pollutants in the proximity of Islamabad Industrial Estate (IEI), Pakistan.

Contaminated air quality, in lieu of massive industrial pollution, is severely attributing to health anomalies in the proximity of industrial units. Cardiovascular Disease (CAD) is rising around industrial units in the planned capital city of Pakistan, Pakistan. To study self-reported CAD in the proximity of Industrial Estate Islamabad (IEI) by equating two distinct study groups as 'Band-I': the residence 0-650 meters and 'Band-II' 650-1300 meters radius around the perimeter of IEI. The perimeters were digitized using Google Earth and GIS. Field survey was conducted on deploying 388 (194 in each Band) close-ended (self-administered) questionnaires at the household level, after adjusting the potential confounding variables. The research calculated odds ratios (ORs) of the CAD at 95% CI. The study's findings of the multiple logistic regression for ORs confirmed a significant increase in CAD problems due to industrial affluents in Band-I than in Band-II which were less severe and less life-threatening. Study confirmed high incidences of high blood pressure and breathing issues (up to 67%), due to accumulation of unhealthy affluents thus leading to heart stroke (Band I = 56.20% and Band II = 60.30%). It is aided by smoking that has increased CAD in Band-I. Societal attributes of knowledge, beliefs, attitudes, and preferences fail to safeguard the local residents amid high concentration of harmful pollutants. As a counter measure the affected respondents engaged in highlighting the issue to the concerned public offices, yet there is a high need on part of the capital government to take mitigative measures to immediately halt the disastrous industrial air emissions to save precious lives.

Deciphering the miRNA-mRNA Interaction Landscape between Breast Cancer and Triple-Negative Breast Cancer: An Integrated Bioinformatics Approach.

Breast cancer (BC) is globally recognized as the second most prevalent form of cancer. It predominantly affects women and can be categorized into distinct types based on the overexpression of specific cancer receptors.The key receptors implicated in this context are the human epidermal growth factor receptor-2 (HER2), estrogen receptor (ER), and progesterone receptor (PR), alongside a particularly intricate subclass known as triple-negative breast cancer (TNBC). This subclassification is critical for the stratification of breast cancer and informs therapeutic decision-making processes. Due to a lack of therapeutic targets, such as growth factor receptors, TNBC is the most aggressive type. Hence, identifying targetable regulators such as miRNAs could pave the way for potential therapeutic interventions. To identify common differentially expressed mRNAs (DE-mRNAs) in BC, including TNBC, we leveraged two data sets from the GEO collection and The Cancer Genome Atlas (TCGA). Significant DE-mRNAs were identified through PPI, MCODE, CytoNCA, and CytoHubba analyses. Following this, miRNAs were predicted using mirDIP. We utilized GSE42568, GSE185645, and TCGA and identified 159 common DE-mRNAs. Using Cytoscape plug-ins, we identified the 10 most significant DE-mRNAs in BC. Using mirDIP, target miRNAs for 10 DE-mRNAs were identified. We conducted an advanced analysis on the TNBC GEO data set (GSE45498) to corroborate the significance of shared DE-mRNAs and DE-miRNAs in TNBC. We identified four downregulated DE-miRNAs, including hsa-miR-802, hsa-miR-1258, hsa-miR-548a-3p, and hsa-miR-2053, significantly associated with TNBC. Our study revealed significant miRNA-mRNA interactions, specifically hsa-miR-802/MELK, hsa-miR-1258/NCAPG, miR-548a-3p/CCNA2, and hsa-miR-2053/NUSAP1, in both BC and TNBC. The observed downregulation of hsa-miR-548a-3p is associated with diminished survival rates in BC patients, emphasizing their potential utility as prognostic indicators. Furthermore, the differential expression of mRNAs, including CCNB2, UBE2C, MELK, and KIF2C, correlates with reduced survival outcomes, signifying their critical role as potential targets for therapeutic intervention in both BC and TNBC. These findings highlight specific regulatory mechanisms that are potentially crucial for understanding and treating these cancer types.

The recent advances in the approach of artificial intelligence (AI) towards drug discovery.

Artificial intelligence (AI) has recently emerged as a unique developmental influence that is playing an important role in the development of medicine. The AI medium is showing the potential in unprecedented advancements in truth and efficiency. The intersection of AI has the potential to revolutionize drug discovery. However, AI also has limitations and experts should be aware of these data access and ethical issues. The use of AI techniques for drug discovery applications has increased considerably over the past few years, including combinatorial QSAR and QSPR, virtual screening, and denovo drug design. The purpose of this survey is to give a general overview of drug discovery based on artificial intelligence, and associated applications. We also highlighted the gaps present in the traditional method for drug designing. In addition, potential strategies and approaches to overcome current challenges are discussed to address the constraints of AI within this field. We hope that this survey plays a comprehensive role in understanding the potential of AI in drug discovery.