Differential Diagnosis of Hematologic and Solid Tumors Using Targeted Transcriptome and Artificial Intelligence.

Diagnosis and classification of tumors is increasingly dependent on biomarkers. RNA expression profiling using next-generation sequencing provides reliable and reproducible information on the biology of cancer. This study investigated targeted transcriptome and artificial intelligence for differential diagnosis of hematologic and solid tumors. RNA samples from hematologic neoplasms (N = 2606), solid tumors (N = 2038), normal bone marrow (N = 782), and lymph node control (N = 24) were sequenced using next-generation sequencing using a targeted 1408-gene panel. Twenty subtypes of hematologic neoplasms and 24 subtypes of solid tumors were identified. Machine learning was used for diagnosis between two classes. Geometric mean naïve Bayesian classifier was used for differential diagnosis across 45 diagnostic entities with assigned rankings. Machine learning showed high accuracy in distinguishing between two diagnoses, with area under the curve varying between 1 and 0.841. Geometric mean naïve Bayesian algorithm was trained using 3045 samples and tested on 1415 samples, and showed correct first-choice diagnosis in 100%, 88%, 85%, 82%, 88%, 72%, and 72% of acute lymphoblastic leukemia, acute myeloid leukemia, diffuse large B-cell lymphoma, colorectal cancer, lung cancer, chronic lymphocytic leukemia, and follicular lymphoma cases, respectively. The data indicate that targeted transcriptome combined with artificial intelligence are highly useful for diagnosis and classification of various cancers. Mutation profiles and clinical information can improve these algorithms and minimize errors in diagnoses.

Supplemental ferulic acid does not affect metabolic markers and improves some oxidative damage parameters in diabetic rats.

This study investigated the differences in health outcomes associated with ferulic acid (FA) supplementation in animals before the induction of diabetes with streptozotocin (STZ) treatment and post-STZ treatment. 18 male Wistar rats were equally distributed into three groups: groups 1 and 2 received FA (50 mg/kg body weight) supplementation one week before STZ treatment (60 mg/kg body weight, intraperitoneal) and one week after STZ treatment, respectively; group 3 received STZ without FA supplementation. FA supplementation was continued for 12 weeks after STZ treatment. The results indicated no difference in glucose and lipid profile with FA supplementation. However, FA supplementation reduced lipid and protein oxidative damage in the heart, liver and pancreas and increased glutathione in the pancreas. The results indicate that while oxidative damages were positively affected by FA, it was not sufficient to improve metabolic markers of diabetes.

Comparative Study of Complete Blood Count Between High-Altitude and Sea-Level Residents in West Saudi Arabia.

The reduction in oxygen partial pressure at high altitudes leads to diminished oxygen saturation in the arteries, stimulating erythropoietin production and erythropoiesis to restore appropriate oxygenation. While many studies have explored acclimatization to high altitude and its effects on complete blood count (CBC) parameters, our research uniquely examined both male and female healthy individuals, emphasizing the novelty of gender-specific observations. We analyzed 1,160 individuals in Taif (Al Hada), east Saudi Arabia, a high-altitude region, and compared them to 1,044 counterparts in Jeddah, at sea level. Our results revealed significant variations in CBC parameters, including white blood count, red blood count, hemoglobin, hematocrit, platelets, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, reflecting the body's hypoxic response. These variations were observed in both genders, with specific differences noted between males and females. For example, NEU (neutrophils), representing the absolute count of a type of white blood cell essential in the immune system's defense, showed significant variations for males. The male results show that the variation in males between the sea level and high altitudes indicated significant p-values for all CBC parameters except NEU between at sea level (Jeddah city), whose p-value was 0.8696, and at high altitude (Taif city, Al Hada). In contrast, MONO (monocytes), another type of white blood cell involved in immune response, and RBC (red blood cells), responsible for oxygen transport, were mentioned but did not show significant variations for females. The full results for females showed significant results (P<0.0001) for BASO, HCT, HGB, MCH, MCHC, MPV, PLT, RDW, and WBC between the sea-level altitude and high altitude for females. Also, EOS and LYM showed significant P-values of 0.0002 and 0.0001, respectively, while MONO, NEU, and RBC indicated no significance between the sea-level altitude and high altitude for females. The p-values of MONO, NEU, and RBC, respectively, were 0.1907, 0.1259, and 0.0677. The results for both genders combined showed significant variations of all CBC parameters (P<0.0001) between the sea-level altitude and high altitude except for MONO, NEU, and RBC, which were not significant for both males and females, with p-values of 0.1589, 0.2911, and 0.0595, respectively. All unhealthy individuals were excluded from the study with any condition that would cause significant changes in CBC parameters and would skew the results, ensuring a focus on physiological adaptations in healthy subjects. By comparing healthy individuals and examining each gender separately, this study contributes valuable insights into high-altitude acclimatization, enhancing our understanding of physiological adaptations and potentially guiding health management in such environments within the normal range.

Karachi Cancer Registry (KCR): Consolidated Data of 5-years 2017-2021.

OBJECTIVE:  To collect and analyse epidemiologic data of all malignancies by age group and gender for the Karachi population to estimate the cancer incidence of 5-years (2017-2021) and identify major risk factors for setting priorities towards cancer control programs. STUDY DESIGN: Observational study. Place and Duration of the Study: Karachi Cancer Registry (KCR) Secretariat, Pakistan Health Research Council (PHRC), JPMC, Karachi, from 2017-2021. METHODOLOGY: Cancer data of seven tertiary care hospitals of Karachi submitted to KCR during the study period were analysed including age, gender, date of first contact, primary site and ICD coding. All the data was cleaned, merged, and analysed. All patients 0-14 years were classified as 'children', all aged 15-19 years were classified as 'adolescents', and those age 20-years and above as 'adults'. Age standardised incidence rates (ASIR) were determined for both genders. RESULTS: During the last five years (2017-2021), a total of 65,886 malignant cases were received. The distributions seen amongst males and females were 33,510 (51%) and 32,376 (49%), respectively with 60,145 (91.3%) tumours found in adults (≥20 years), 4844 (7.3%) in children, and 897 (1.4%) in adolescents. The three most common tumour sites were oral, liver, and colorectal in males; breast, oral and ovary in females; bone, brain and connective tissue in adolescents; and leukaemia, brain and bone in children. The overall ASIR (%) in males was 89.20 for adults, 9.19 for children, and 1.61 for adolescents. The overall ASIR (%) in females was 93.44 for adults, 5.45 for children, and 1.11 for adolescents. CONCLUSION: Oral cancer, a largely preventable cancer is the leading cancer in males while breast cancer is the leading cancer in females followed by oral cancer. In adolescents and children, the incidence closely matches most of the world. KEY WORDS: Karachi, Cancer registry, Oral cancer, Breast cancer, Age-standerdised ratio.

Appropriateness of troponin testing in emergency department at a tertiary care hospital in Saudi Arabia.

OBJECTIVES: To assess the appropriateness of troponin testing in the Emergency Department (ED) at King Saud Medical City, Riyadh, Saudi Arabia. METHODS: This record-based cross-sectional study examined the electronic records of adult patients who underwent a troponin test following admission to hospital's ED from January to March 2020. RESULTS: A total of 367 troponin tests were ordered for 233 patients. Majority of these orders were appropriate (55%) while the remaining (45%) were adjudged as inappropriate. Among the inappropriate orders, majority were single (61%) compared to serial ones (39%). Overall, there were 166 inappropriate orders and the estimated direct monthly cost for inappropriate testing was 49,800 Saudi Riyals in the emergency department alone. CONCLUSION: Approximately half of the troponin tests ordered in the ED were inappropriate. The overall financial burden of inappropriate testing greatly impacts patient management and resource utilization. These findings emphasize the pressing need for institutional clinical guidelines to guide appropriate use of troponin testing.

Effects of Obesity and Diabesity on Ventricular Muscle Structure and Function in the Zucker Rat.

(1) Background: Cardiovascular complications are a leading cause of morbidity and mortality in diabetic patients. The effects of obesity and diabesity on the function and structure of ventricular myocytes in the Zucker fatty (ZF) rat and the Zucker diabetic fatty (ZDF) rat compared to Zucker lean (ZL) control rats have been investigated. (2) Methods: Shortening and intracellular Ca2+ were simultaneously measured with cell imaging and fluorescence photometry, respectively. Ventricular muscle protein expression and structure were investigated with Western blot and electron microscopy, respectively. (3) Results: The amplitude of shortening was increased in ZF compared to ZL but not compared to ZDF myocytes. Resting Ca2+ was increased in ZDF compared to ZL myocytes. Time to half decay of the Ca2+ transient was prolonged in ZDF compared to ZL and was reduced in ZF compared to ZL myocytes. Changes in expression of proteins associated with cardiac muscle contraction are presented. Structurally, there were reductions in sarcomere length in ZDF and ZF compared to ZL and reductions in mitochondria count in ZF compared to ZDF and ZL myocytes. (4) Conclusions: Alterations in ventricular muscle proteins and structure may partly underlie the defects observed in Ca2+ signaling in ZDF and ZF compared to ZL rat hearts.

Structural lesions and changing pattern of expression of genes encoding cardiac muscle proteins are associated with ventricular myocyte dysfunction in type 2 diabetic Goto-Kakizaki rats fed a high-fat diet.

Given the clinical prevalence of type 2 diabetes and obesity and their association with high mortality linked to cardiovascular disease, the aim of the study was to investigate the effects of feeding type 2 diabetic Goto-Kakizaki (GK) rats either high- or low-fat diets on cardiomyocyte structure and function. The GK rats were fed either a high-fat diet (HFD) or a low-fat diet (LFD) from the age of 2 months for a period of 7 months. The GK-HFD rats gained more weight, ate less food and drank less water compared with GK-LFD rats. At 7 months, non-fasting blood glucose was higher in GK-LFD (334 ± 35 mg dl(-1)) compared with GK-HFD rats (235 ± 26 mg dl(-1)). Feeding GK rats with a HFD had no significant effect on glucose clearance following a glucose challenge. Time-to-peak (t(peak)) shortening was reduced in myocytes from GK-HFD (131.8 ± 2.1 ms) compared with GK-LFD rats (144.5 ± 3.0 ms), and time-to-half (t(1/2)) relaxation of shortening was also reduced in myocytes from GK-HFD (71.7 ± 6.9 ms) compared with GK-LFD rats (86.1 ± 3.6 ms). The HFD had no significant effect on the amplitude of shortening. The HFD had no significant effect on t(peak), t(1/2) decay, amplitude of the Ca(2+) transient, myofilament sensitivity to Ca(2+), sarcoplasmic reticulum Ca(2+) content, fractional release of Ca(2+) and the rate of Ca(2+) uptake. Structurally, ventricular myocytes from GK-HFD rats showed extensive mitochondrial lesions, including swelling, loss of cristae, and loss of inner and outer membranes, resulting in gross vacuolarization and deformation of ventricular mitochondria with a subsequent reduction in mitochondrial density. Expression of genes encoding various L-type Ca(2+) channel proteins (Cacnb2) and cardiac muscle proteins (Myl2 and Atp2a1) were downregulated in GK-HFD compared with GK-LFD rats. Structural lesions and changed expression of genes encoding various cardiac muscle proteins might partly underlie the altered time course of myocyte shortening and relaxation in myocytes from GK-HFD compared with GK-LFD rats.

Lip and oral cavity cancers (C00-C06) from a mega city of Pakistan: Ten-year data from the Dow Cancer Registry.

OBJECTIVE: The objective of this report is to provide an overview of lip and oral cavity cancer in Karachi, the largest city in Pakistan. METHODS: This study was undertaken at the Dow Cancer Registry. During 2010-2019, all patients who were residents of Karachi who had been diagnosed with lip and oral cavity cancer were registered and recruited for this study. The data were entered in SPSS and MS Excel sheets to investigate frequencies, age-standardized-rates (ASR) and other clinicopathological parameters. The data from our study were compared with the ASR of lip and oral cavity cancer from selected Asian countries. RESULTS: During the defined period, 22,858 cancer cases were registered. Of these, 4,400 (19.2%, ASR 28.0) were lip and oral cavity cancer (the most common type found in males and the second most common type in females), of which 2,986 (67.8%) were found in males, while 1,414 (32.1%) were reported in females. Squamous cell carcinoma was the most common type (97.7%). Most tumours were moderately differentiated (67.7%) followed by poorly (16.6%), and well differentiated (15.7%). CONCLUSION: We report an alarmingly high ASR of lip and oral cavity cancer in Karachi as compared to Pakistan as a whole and other Asian countries.

Expression of miR-31 in saliva-liquid biopsy in patients with oral squamous cell carcinoma.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is a commonly reported cancer in men and is second only to breast cancer in women in Pakistan.. Investigations for identifying biomarkers of OSCC are essential for diagnostic, therapeutic, or prognostic significance. This study aims to examine the miR-31 expression in the pre- and post-operative OSCC patients and correlate this expression with clinicopathological characteristics. METHODS: Patients with histopathologically confirmed OSCC who had undergone surgical resections of tumours were recruited. A total of 40 saliva samples (pre- and post-operative) were collected from 19 patients and two healthy individuals. Levels of salivary miR-31 expressions were examined through quantitative reverse transcription polymerase chain reaction. RESULTS: The salivary miR-31 expression was significantly higher in the preoperative patients than in postoperative patients (p < 0.001). However, no significant correlation had been found between the salivary miR-31 expression and clinicopathological characteristics (p > 0.05). CONCLUSION: Our data suggest that miR-31 can be used as an adjunct non-invasive marker to monitor surgery outcomes during postoperative follow-up in patients with OSCC.

Calcium signaling in endocardial and epicardial ventricular myocytes from streptozotocin-induced diabetic rats.

AIMS/INTRODUCTION: Abnormalities in Ca2+ signaling have a key role in hemodynamic dysfunction in diabetic heart. The purpose of this study was to explore the effects of streptozotocin (STZ)-induced diabetes on Ca2+ signaling in epicardial (EPI) and endocardial (ENDO) cells of the left ventricle after 5-6 months of STZ injection. MATERIALS AND METHODS: Whole-cell patch clamp was used to measure the L-type Ca2+ channel (LTCC) and Na+ /Ca2+ exchanger currents. Fluorescence photometry techniques were used to measure intracellular free Ca2+ concentration. RESULTS: Although the LTCC current was not significantly altered, the amplitude of Ca2+ transients increased significantly in EPI-STZ and ENDO-STZ compared with controls. Time to peak LTCC current, time to peak Ca2+ transient, time to half decay of LTCC current and time to half decay of Ca2+ transients were not significantly changed in EPI-STZ and ENDO-STZ myocytes compared with controls. The Na+ /Ca2+ exchanger current was significantly smaller in EPI-STZ and in ENDO-STZ compared with controls. CONCLUSIONS: STZ-induced diabetes resulted in an increase in amplitude of Ca2+ transients in EPI and ENDO myocytes that was independent of the LTCC current. Such an effect can be attributed, at least in part, to the dysfunction of the Na+ /Ca2+ exchanger. Additional studies are warranted to improve our understanding of the regional impact of diabetes on Ca2+ signaling, which will facilitate the discovery of new targeted treatments for diabetic cardiomyopathy.