Significant Association of PD-L1 With CD44 Expression and Patient Survival: Avenues for Immunotherapy and Cancer Stem Cells Downregulation in Pancreatic Cancers.

Background: Pancreatic cancers are known for their aggressive nature. This aggressiveness may be attributed to the presence of cancer stem cells (CSCs), which promote relapse, metastasis, and resistance to chemotherapy. Targeting CSCs is essential to reverse this aggressiveness in pancreatic malignancies. Literature highlights the association of PD-L1 expression with CSCs in various cancers, suggesting immunotherapy as a promising therapeutic approach. This study is aimed at investigating the potential of immunotherapy in pancreatic cancers by examining its association with selected CSC marker expression. Method: A retrospective cohort study was conducted involving 56 patients with confirmed diagnoses of pancreatic cancers at Aga Khan University Hospital from January 2015 to October 2022. After exclusions, based on refusal to provide consent or incomplete follow-up data, 38 patients were enrolled in the study. Immunohistochemistry was performed on formalin-fixed paraffin-embedded (FFPE) tumor tissue samples to assess the expression of CSC markers (CD133, CD44, and L1CAM) and immune checkpoint inhibitor marker (PD-L1). Statistical analysis was employed to determine associations between marker expression, clinical factors, and overall survival. Results: The study revealed that 86.8% of pancreatic cancer cases exhibited positive PD-L1 expression. Moreover, a significant association of PD-L1 expression was observed with the presence of CD44 protein (p = 0.030), as well as with the overall survival of patients (p = 0.023). Conclusion: Our findings show a significant association of PD-L1 with CD44 marker expression as well as patient survival. This research shows the potential to serve as the foundation for investigating the efficacy of immunotherapy in reducing CD44-expressing CSCs in pancreatic cancer, potentially enhancing patient outcomes.

Estimation of 10-Year Fracture Risk with and without Bone Mineral Density in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is the most common inflammatory arthritis affecting 0.5-1.0% of the general population worldwide and although RA is properly considered a disease of the joints, it can cause a variety of extra-articular manifestations. This study was performed to find out any discrepancy in fracture risk estimates with and without bone mineral density (BMD) in rheumatoid arthritis (RA) patients. This observational cross-sectional study was carried out in the Department of Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh from July 2013 to July 2015. Total 65 consecutive patients with RA fulfilling ACR/EULAR criteria aged 40-90 year were recruited. Ten year fracture risk of these patients was evaluated by the FRAX score with and without BMD and differences were observed. FRAX score without BMD revealed that major fracture risk was low in 58(89.2%) patients, moderate in 7(10.8%) patients but re-estimation with BMD revealed that 55(84.6%) patients remained in low risk group, 8(12.3%) patients in moderate risk group and 2(3.1%) patients went to the high risk group. In case of hip fracture risk without BMD, risk was low in 58(89.2%) patients, high in 7(10.8%) patients; but with BMD, 50(76.9%) patients remained in low risk group but risk of 15(23.1%) patients became high. Almost all the high risk patients (93.3%) were ≥55 years of age. Increasing age, female sex, disease duration and use of steroid were positively correlated with increased FRAX score where as high BMI and high BMD were associated with low FRAX score. But in multivariate analysis it was found that only relation with age was at statistically significant level. Significant numbers of patients with rheumatoid arthritis have high risk of fracture especially hip fracture. The mean of FRAX score increased in both major & hip osteoporotic fracture risk after adding BMD. More than half of the patients above fifty five years or more had high risk of fracture. So, BMD should be done in patients aged more than fifty five.

Longitudinal disparities in social determinants of health and COVID-19 incidence and mortality in the United States from the three largest waves of the pandemic.

The United States experienced at least five COVID-19 waves linked with different mutated SARS-CoV-2 variants including Alpha, Delta and Omicron. In addition to the variants, the intensity, geographical distribution, and risk factors related to those waves also vary within socio-demographic characteristics and timeframes. In this project, we have examined the spatial and temporal pattern of COVID-19 in the USA and its associations with Social Determinants of Health (SDoH) by utilizing the County Health Rankings & Roadmaps (CHRR) dataset. Our epidemiologic investigation at the county level showed that the burden of COVID-19 cases and deaths is higher in counties with high percentages of smoking, number of preventable hospital stays, primary care physician rate, the average daily density of PM2.5 and percentages of high proportions of Hispanic residents. In addition, the analysis also demonstrated that COVID-19 incidence and mortality had distinct characteristics in their association with SDoH variables. For example, the percentages of the population 65 and older had negative associations with incidence while a significant positive association with mortality. In addition to the elderly population, median household income, unemployment, and number of drug overdose deaths showed a mixed association with COVID-19 incidence and mortality. Our findings validate several influential factors found in the existing social epidemiology literature and highlight temporal associations between SDoH variables and COVID-19 incidence and mortality not yet frequently studied.

Feasibility and outcomes of Desarda vs Lichtenstein hernioplasty by local anesthesia for inguinal hernia: a noninferiority randomized clinical trial.

INTRODUCTION: The Desarda autologous tissue repair is comparable to the Lichtenstein hernioplasty for inguinal hernia regarding recurrence, chronic groin pain, and return to work activities. This study was designed to establish the outcomes of Desarda's repair versus Lichtenstein's hernioplasty concerning post-operative recovery to normal gait and its feasibility under local anesthesia (LA). MATERIALS AND METHODS: This study was a single-center, prospective, double-blinded, non-inferiority, randomized trial. Patients undergoing open hernia repair for primary inguinal hernia were included. Patients were randomly assigned and followed up for 2 years. The primary endpoint was the time to return to normal gait post-surgery with comfort (non-inferiority margin fixed as 0.5 days). The secondary outcomes studied were post-operative pain score, the time required to return to work (all previously performed activities), and surgical-site occurrences (SSO). RESULTS: One hundred ten eligible patients were randomly assigned [56 patients (50.9%) in the Desarda group and 54 patients (49.1%) in the Lichtenstein group]. All the procedures were safely performed under LA. The median (interquartile range) time for resuming gait post-surgery with comfort was 5 days in the Desarda vs 4 days in Lichtenstein's arm (P = 0.16), thereby failing to demonstrate non-inferiority of Desarda against Lichtenstein hernioplasty. However, there were no significant differences in days to return to work, SSO, chronic groin pain, and recurrence within two years of surgery. CONCLUSIONS AND RELEVANCE: This study could not demonstrate the non-inferiority of the Desarda repair versus Lichtenstein hernioplasty regarding the time taken to return to normal gait. Comparing the days to return to work, pain score, SSO, and chronic groin pain, including recurrence rate, Desarda repair faired equally with Lichtenstein hernioplasty, thereby highlighting its feasibility and efficacy under LA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03512366.

Spatio-temporal changes of winter and spring phytoplankton blooms in Arabian sea during the period 1997-2020.

Arabian Sea (AS) experiences Chlorophyll-a (Chl-a) blooms during winter and early spring (November-March) mainly due to the changes induced by seasonally reversing monsoon winds and associated processes. The seasonal blooms exhibit distinct regional patterns in their onset, duration, intensity and peak period. Recent changes in ocean dynamics and plankton composition have inflicted adverse effects in the distribution of Chl-a concentration in AS. Here, we analyse the long-term spatio-temporal changes in winter and early spring bloom events during the period 1997-2020, and evaluate the role of sea surface temperature (SST), mixed layer depth (MLD), sea surface salinity, winds, mesoscale eddies and surface currents on these bloom occurrences. We observe a significant reduction in these blooms, which started in the early 2000s and intensified in the last decade (2010-2020), with a notable drop in the adjacent gulfs (Gulf of Aden: 1.38 ± 0.7 × 10-5 mg m-3 yr-1, Gulf of Oman: 4.71 ± 1.35 × 10-6 mg m-3 yr-1) and West coast of India (-6.71 ± 2.85 × 10-6 mg m-3 yr-1). The MLD and ocean temperature are the major factors that govern bloom in Gulf of Oman and open waters. Conversely, the coastal upwelling and eddies drive blooms in Gulf of Aden. The winter cooling trigger the bloom in the northern Indian west coast, but the inter-basin exchange of surface waters through the West Indian Coastal Current inhibits its southward spread. This study, therefore, reveals unique processes that initiate and control the winter and early spring blooms in different regions of AS. The ongoing warming of AS could contribute to further decline in these seasonal blooms, which would be a great concern for regional marine productivity and associated regional food security.

Immunohistochemical analysis of a panel of cancer stem cell markers and potential therapeutic markers in pancreatic ductal adenocarcinoma.

PURPOSE: Pancreatic Ductal Adenocarcinoma (PDAC) is the most common type of pancreatic malignancies. It is known for its aggressive nature and high mortality rate. This calls for an urgent need of new prognostic and therapeutic markers that can be targeted for personalized treatment of the patient. METHODS: Among 142 patients diagnosed with pancreatic cancers at Aga Khan University Hospital, a total of 62 patients were selected based on their confirmed diagnosis of PDAC. Immunohistochemistry was performed on Formalin-Fixed Paraffin-Embedded (FFPE) sections using selected antibodies (CD44, CD133, L1CAM, HER2, PD-L1, EGFR, COX2 and cyclin D1). All the slides were scored independently by two pathologists as per the set criteria. RESULTS: Expression of all cancer stem cell markers was found to be significantly associated with one or more potential therapeutic markers. CD44 expression was significantly associated with HER2 (p = 0.032), COX2 (p = 0.005) and EGFR expression (p = 0.008). CD133 expression also showed significant association with HER2 (p = 0.036), COX2 (p = 0.004) and EGFR expression (p = 0.018). L1CAM expression was found to be associated with expression of COX2 (p = 0.017). None of the proteins markers showed association with overall survival of the patient. On the other hand, among the clinicopathological characteristics, histological differentiation (p = 0.047), lymphovascular invasion (p = 0.021) and perineural invasion (p = 0.014) were found to be significantly associated with patient's overall survival. CONCLUSION: Internationally, this is the first report that assesses the selected panel of cancer stem cell markers and potential therapeutic targets in a single study and evaluates its combined expression. The study clearly demonstrates association between expression of cancer stem cell markers and therapeutic targets hence paves a way for precision medicine for pancreatic cancer patients.

A user-guided personalization methodology to facilitate new smart home occupancy.

Smart homes are becoming increasingly popular in providing people with the services they desire. Activity recognition is a fundamental task to provide personalised home facilities. Many promising approaches are being used for activity recognition; one of them is data-driven. It has some fascinating features and advantages. However, there are drawbacks such as the lack of ability to providing home automation from the day one due to the limited data available. In this paper, we propose an approach, called READY (useR-guided nEw smart home ADaptation sYstem) for developing a personalised automation system that provides the user with smart home services the moment they move into their new house. The system development process was strongly user-centred, involving users in every step of the system's design. Later, the user-guided transfer learning approach was introduced that uses an old smart home data set to enhance the existing smart home service with user contributions. Finally, the proposed approach and designed system were tested and validated in the smart lab that showed promising results.

The psychological impact of Behçet's disease.

BACKGROUND: Bechet's disease (BD), a chronic multiorgan involving disease, has a significant impact on quality of life in spite of effective treatment modalities. Disease manifestations such as arthritis, orogenital ulcerations, rashes, angiitis, and neurological involvement affect health-related quality of life (HRQoL) through its impact on depression, anxiety, and fatigue. OBJECTIVES: We aimed explore the psychological impact of BD, taking into consideration the effect on the HRQoL, as well as the association with depression, anxiety, wellbeing, and fatigue. METHODS: This is a narrative review of the literature that looks into the association of BD on the HRQoL including all studies that have assessed such as association. RESULTS/FINDINGS: Depression and anxiety are prevalent among patients with BD, and contribute significantly to fatigue, a common symptom among BD patients. In addition, the psychological wellbeing is affected by the disease, however, more studies are needed to assess this relationship. CONCLUSION: Depression and anxiety are strongly associated with BD, and contribute significantly to fatigue, a common symptom among BD patients. In addition, the psychological wellbeing is affected by the disease, however, more studies are needed to assess this relationship. Besides, the controlling factors of the psychological impact are still to be deciphered.

High CD44 Immunoexpression Correlates with Poor Overall Survival: Assessing the Role of Cancer Stem Cell Markers in Oral Squamous Cell Carcinoma Patients from the High-Risk Population of Pakistan.

Oral squamous cell carcinoma (OSCC) is a top-ranked cancer in the Pakistani population, and patient survival has remained unchanged at ∼50% for several decades. Recent advances have claimed that a subset of tumour cells, called cancer stem cells (CSCs), are responsible for tumour progression, treatment resistance, and metastasis, which leads to a poor prognosis. This study investigated the impact of CSC markers expression on overall survival (OS) and disease-free survival (DFS) of OSCC patients. Materials and Methods. Immunohistochemistry was used to evaluate CD44, CD133, L1CAM, and SOX2 expression in a well-characterized cohort of 100 Pakistani patients with primary treatment naïve OSCC. The immunoreactivity for each marker was correlated with patient clinicopathologic characteristics, oral cancer risk chewing habits, and survival. The minimum follow-up time for all patients was five years, and survival estimates were calculated using the Kaplan-Meier method and Cox proportional hazards model. Results. In this cohort of 100 patients, there were 57 males and 43 females. The median OS and DFS time durations observed were 64 and 52.5 months, respectively. Positive expression for CD44, CD133, L1CAM, and SOX2 was observed in 33%, 23%, 41%, and 63% of patients. High CD44 expression correlated with decreased OS (P=0.047) but did not influence DFS. However, CD133, L1CAM, and SOX2 had no effect on either OS or DFS. Tonsils, nodal involvement, and AJCC stage were independent predictors of worse OS and DFS both. Conclusion. Of the CSC markers investigated here, only CD44 was a predictor for poor OS. CD44 was also associated with advanced AJCC and T stages. Interestingly, CD133 was significantly lower in patients who habitually consumed oral cancer risk factors.

Out-of-pocket payment for healthcare among urban citizens in Dhaka, Bangladesh.

OBJECTIVES: Out-of-pocket (OOP) payment is the major payment strategy for healthcare in Bangladesh, and the share of OOP expenditure has increased alarmingly. Dhaka is recognised as one of the fastest-growing megacities in the world. The objective of this study is to capture the self-reported illnesses among urban citizens and to identify whether and to what extent socioeconomic, demographic and behavioural factors of the population influence OOP healthcare expenditures. SUBJECT AND METHODS: This study utilises cross-sectional survey data collected from May to August 2019 in urban Dhaka, Bangladesh. A total of 3,100 households were randomly selected. Simple descriptive statistics including frequencies, percentage, mean (95% CI), median and inter-quartile range were presented. Bivariate analysis and multivariate regression models were employed. RESULTS: We observed that acute illnesses (e.g., fever, flu/cough) were dominant among participants. Among the chronic illnesses, approximately 9.6% of people had diabetes, while 5.3% had high/low blood pressure. The richest quintile only spent 5.2% of their household income on healthcare, while the poorest households spent approximately six times more than the richest households. We noted that various factors such as marital status, religion, source of care, access to safe water, income quintile and even the location of households had a significant relationship with OOP expenditure. CONCLUSIONS: Our findings can serve as important source of data in terms of disease- specific symptoms and out-of-pocket cost among urban citizens in Dhaka. The people belonging to wealthier households tended to choose better healthcare facilities and spend more. A pro-poor policy initiative and even an urban health protection scheme may be necessary to ensure that healthcare services are accessible and affordable, in line with the Bangladesh National Urban Health Strategy.

Case-Control Study to Evaluate Zinc Deficiency as a Risk Factor for Oxygen Requirement in Patients with COVID-19.

Zinc is one of the important trace elements of blood. It helps in maturation of immune system in our body. In the past studies originate the relationship between viral disease and serum zinc deficiency. This was a multicenter case-control study to measure the serum zinc level of COVID-19 patients with different respiratory supports and to evaluate the Odds Ratio (OR) and Relative risk (RR) of zinc deficiency for oxygen requirement for COVID-19 patients. Study places were COVID-19 unit of three tertiary hospitals of Sylhet, a Northern district of Bangladesh. There were 30 controls and 90 cases in this study. The mean zinc level of cases (53-38mcg/dl) was significantly (p=0.000072) lower than the level of controls (73-23mcg/dl). The mean zinc level of the COVID-19 patients required oxygen (49-33mcg/dl) was significantly (p=0.0054) lower than the patients were not treated by oxygen therapy (64-51mcg/dl). The RR of getting affected by COVID-19 was 1-91 for the low zinc level people. Among the COVID-19 affected participants the lower zinc level people had a RR of 1-93 to receive oxygen supplementation. Lower zinc level people are more likely to be affected by COVID-19 in comparison to the normal zinc level people. Among the COVID-19 patients the lower zinc level people had nearly double (RR 1-93) risk of becoming hypoxic and eventually prone for oxygen support.

Genetic landscape of pancreatic adenocarcinoma patients: a pilot study from Pakistan.

BACKGROUND: Pancreatic adenocarcinoma is one of the most aggressive malignancies with extremely low survival rate. Studies have shown that the exploration of key genes can provide a basis for targeted treatment of these patients. The genomic architecture of the Pakistani pancreatic adenocarcinoma patients remains unexplored. Keeping the scenario in place, the current study aims to analyse 88 cancer related genes in Pakistani pancreatic adenocarcinoma patients in order to elucidate candidate gene(s) for targeted molecular therapy. METHODS AND RESULTS: A total 18 patients were included in the study initially and FFPE tumor samples were obtained. After confirmation of diagnosis and appropriate tumor content, DNA was extracted. Based on the quality and quantity of the extracted DNA, six pancreatic adenocarcinoma tumor samples were selected. Following to this, all the samples were subjected to targeted sequencing (Axen Cancer Panel 1). Variant detection was done and clinical significance of identified variants was assessed using ClinVar database. Targeted sequencing of tumor samples revealed a total of 29 alterations in the coding region of various genes. Among these five pathogenic variants were found in KRAS, BRCA1, TP53 and APC genes. CONCLUSION: This is the first study that explores genes involved in pancreatic adenocarcinoma from the Pakistani population. Results obtained from the pilot study can guide us about the key genetic players in the Pakistani pancreatic adenocarcinoma population. This can lead to our better understanding of the molecular targeted therapies for these patients and designing future researches on larger sample size.