Secondary findings in a large Pakistani cohort tested with whole genome sequencing.

Studies on genomic secondary findings (SFs) are diverse in participants' characteristics, sequencing methods, and versions of the ACMG SF list. Based on whole genome sequencing and the version 3.1 of the ACMG SF list, we studied SFs in 863 individuals from five different regions in Pakistan. We identified 24 ACMG SFs in 23 (2.7%) of 863 individuals: 18 of 24 were related to cardiovascular disease and four to cancer syndromes. In addition to ACMG SFs, we identified 16 (1.9%) participants with pathogenic and likely pathogenic variants in genes that were not related to the participants' clinical conditions but with clear medical actionability (non-ACMG SFs): 4 of 16 were related to eye diseases, two to metabolic disorders, and two to urinary system disorders. By testing a large Pakistani cohort with whole genome sequencing, we concluded that in countries such as Pakistan, the ACMG SF list could be expanded, and our non-ACMG SF list is one example.

Kinetic and thermodynamic studies of novel acid phosphatase isolated and purified from Carthamus oxyacantha seedlings.

Acid phosphatase (ACP) is a key enzyme in the regulation of phosphate feeding in plants. In this study, a new ACP from C. oxyacantha was isolated to homogeneity and biochemically described for the first time. Specific activity (283 nkat/mg) was found after 2573 times purification fold and (17 %) yield. Using SDS-PAGE under denaturing and nondenaturing conditions, ACP was isolated as a monomer with a molecular weight of 36 kDa. LC-MS/MS confirmed the presence of this band, suggesting that C. oxycantha ACP is a monomer. The enzyme could also hydrolyze orthophosphate monoester with an optimal pH of 5.0 and a temperature of 50 °C. Thermodynamic parameters were also determined (Ea, ΔH°, ΔG°, and ΔS°). ACP activity was further studied in the presence of cysteine, DTT, SDS, EDTA, ß-ME, Triton-X-100 H2O2, and PMSF. The enzyme had a Km of 0.167 mM and an Ea of 9 kcal/mol for p-nitrophenyl phosphate. The biochemical properties of the C. oxyacantha enzyme distinguish it from other plant acid phosphatases and give a basic understanding of ACP in C. oxyacantha. The results of this investigation also advance our knowledge about the biochemical significance of ACP in C. oxyacantha. Thermal stability over a wide pH and temperature range make it more suitable for use in harsh industrial environments. However, further structural and physiological studies are anticipated to completely comprehend its important aspects in oxyacantha species.

Stent as a Novel Technology for Coronary Artery Disease and Their Clinical Manifestation.

Coronary artery disease (CAD) is a cardiovascular disease of the blood vessels that makes vessels, narrow and hardened and difficult to supply blood to the heart. The epidemiology of CAD disease is a common clinical syndrome of a global health priority and the burden is increasing at an alarming rate worldwide. The prevalence of CAD not only increases mortality, morbidity and worsens the patient quality of life but also puts a huge burden on the overall healthcare system. The novel risk factors include: cholesterol level, cigarette smoking, diabetics, obesity, and hypertension, respectively are the causative agents of CAD. Furthermore, the etiology of CAD is also a very complex process and several interrelated etiological factors are involved in the pathogenesis of CAD. The signs and symptoms of CAD appear like angina, heart failure, and dyspnea, myocardial infarction, and arrhythmia, respectively. The management and diagnosis of CAD include different types of medications that are used nowadays for the treatment of this disease. The highlights of the present review focused on stent technology and its useful applications. Finally, we also addressed the benefits of the stent, and its potential complications, effectiveness, indication, and contraindication that play a significant role in the recovery of CAD disease.

State-of-the-Art Challenges and Perspectives in Multi-Organ Cancer Diagnosis via Deep Learning-Based Methods.

Thus far, the most common cause of death in the world is cancer. It consists of abnormally expanding areas that are threatening to human survival. Hence, the timely detection of cancer is important to expanding the survival rate of patients. In this survey, we analyze the state-of-the-art approaches for multi-organ cancer detection, segmentation, and classification. This article promptly reviews the present-day works in the breast, brain, lung, and skin cancer domain. Afterwards, we analytically compared the existing approaches to provide insight into the ongoing trends and future challenges. This review also provides an objective description of widely employed imaging techniques, imaging modality, gold standard database, and related literature on each cancer in 2016-2021. The main goal is to systematically examine the cancer diagnosis systems for multi-organs of the human body as mentioned. Our critical survey analysis reveals that greater than 70% of deep learning researchers attain promising results with CNN-based approaches for the early diagnosis of multi-organ cancer. This survey includes the extensive discussion part along with current research challenges, possible solutions, and prospects. This research will endow novice researchers with valuable information to deepen their knowledge and also provide the room to develop new robust computer-aid diagnosis systems, which assist health professionals in bridging the gap between rapid diagnosis and treatment planning for cancer patients.

Outcomes of Revascularization and Factors Associated With Major Amputation in Patients With Lower Limb Arterial Injury: A Single-Center Retrospective Analysis.

Objective To identify the amputation rates and causative factors for failed revascularization leading to amputation in patients undergoing primary limb salvage procedures for lower-extremity vascular injuries. Methods This retrospective study was conducted at the vascular surgery department, Shaheed Mohtarma Benazir Bhutto (SMBB) Institute of Trauma, Karachi, Pakistan. The data were collected from hospital record using the non-probability sampling technique. Patients aged 17-70 years, undergoing primary revascularization during April 2016 to March 2021, were included in the study. Patients with crush injuries/non-salvageable limbs underwent primary amputation, isolated deep femoral artery or crural arteries (non-limb threatening) injuries, and non-traumatic injuries like intravenous drug-induced or iatrogenic injuries were excluded. The data analysis is done using SPSS Version 20.0 (IBM Corp., Armonk, NY, USA). A P-value of <0.05 was considered as significant. Results This study includes 56 patients of mean age 30.82 ± 9.29 years with male gender four times more affected than their counterpart. About 32% of patients were smokers, while 58% of patients had no co-morbidities. All patients presented with a mean time of 7.66 ± 1.69 hours of injury with an average of 1.14 arterial segments involved. The most frequent artery involved was popliteal artery (both above and below the knee), followed by superficial femoral artery injury constituting 50% and 26%, respectively, with arterial laceration and transection being common findings on exploration. Out of 56 patients, 27 (48.2%) had open fractures, 21 (37.5% ) closed fractures, and eight patients (14.3 % ) presented with dislocation as associated injuries. Following the procedure, secondary amputation was recorded in 18 (32.1%) patients. Thrombosis and infection were the leading causes of revascularization failure. Type of injury, segment of arterial injury, and associated bony injuries were associated with limb amputation. Conclusion Type and site of injury along with concomitant bony injuries are associated with major amputations after revascularization in lower-extremity arterial injuries.

Computer Vision-Based Microcalcification Detection in Digital Mammograms Using Fully Connected Depthwise Separable Convolutional Neural Network.

Microcalcification clusters in mammograms are one of the major signs of breast cancer. However, the detection of microcalcifications from mammograms is a challenging task for radiologists due to their tiny size and scattered location inside a denser breast composition. Automatic CAD systems need to predict breast cancer at the early stages to support clinical work. The intercluster gap, noise between individual MCs, and individual object's location can affect the classification performance, which may reduce the true-positive rate. In this study, we propose a computer-vision-based FC-DSCNN CAD system for the detection of microcalcification clusters from mammograms and classification into malignant and benign classes. The computer vision method automatically controls the noise and background color contrast and directly detects the MC object from mammograms, which increases the classification performance of the neural network. The breast cancer classification framework has four steps: image preprocessing and augmentation, RGB to grayscale channel transformation, microcalcification region segmentation, and MC ROI classification using FC-DSCNN to predict malignant and benign cases. The proposed method was evaluated on 3568 DDSM and 2885 PINUM mammogram images with automatic feature extraction, obtaining a score of 0.97 with a 2.35 and 0.99 true-positive ratio with 2.45 false positives per image, respectively. Experimental results demonstrated that the performance of the proposed method remains higher than the traditional and previous approaches.

Selective or Routine Histology of Cholecystectomy Specimens for Diagnosing Incidental Carcinoma of Gallbladder and Correlation with Careful Intraoperative Macroscopic Examination? A Systematic Review.

BACKGROUND: Selective or Routine histology of cholecystectomy specimens for benign gallbladder disease has always been a matter of debate because of the low prevalence and bad prognosis associated with gall bladder carcinoma. The objective of this study is to ascertain whether selective histology can be preferred over Routine histology without any harm. METHODS: This systematic review is conducted according to PRISMA's checklist; relevant articles were searched in the database until September 1 2020 in PubMed, Scopus, Science Direct, and Web of Science databases, manually, with search queries and without date restrictions. Studies included in this systematic review involved patients who underwent cholecystectomy for benign gallbladder disease and were diagnosed with gallbladder carcinoma incidentally either after selective or routine histology of the gallbladder. RESULTS: A total of 24 routine or selective histology recommending studies were selected for the systematic review after following the inclusion and exclusion criteria. These studies comprised 77,213 numbers of patients and 486 numbers of Malignancies. These studies correlate the number of IGBC diagnosed histologically with the number of IGBC's that were suspected by the surgeons intraoperative by macroscopy. Routine recommending studies show a significant number of IGBC diagnosed histologically as missed by surgeons whereas the selective recommending studies show most of the histologically diagnosed IGBC already suspected by the surgeons intraoperative. When comparing the macroscopic details of the IGBC's between routine and selective studies, we found that there was significant overlap. Most of the findings missed by the surgeons as suspicious in routine studies were suspected by the surgeons involved in selective histology recommending studies. Thereby, favouring selective histology and emphasizing the need for careful intraoperative macroscopy for suspecting IGBC. CONCLUSION: Selective Histological examination of cholecystectomy specimens can be preferred if a careful intraoperative macroscopic examination is done and patient risk factors are taken into consideration.

Outcomes of Femoral Artery Pseudoaneurysm in Intravenous Drug Abusers Managed at a Tertiary Care Center.

Objectives The aim of this study was to assess the effects of ligation and excision of femoral artery pseudoaneurysm without revascularization in intravenous drug abusers presenting in the tertiary care center. Methods This was a retrospective study conducted at Shaheed Mohtarma Benazir Bhutto Institute, Karachi, Pakistan, and included 119 patients admitted for vascular injuries of the groin between June 2016 and June 2020. Data collected from the hospital's medical records included all intravenous drug addicts presented with mass near or at groin area only, while other pseudoaneurysm locations secondary to vascular trauma, arteriovenous fistula, and hemodialysis were excluded. SPSS Version 20.0 (IBM Corp., Armonk, NY, USA) was used for data analysis. Results This study included 119 patients, all of whom presented and admitted to the Accident and Emergency Department, with a mean age of about 32 years ± 11.34 years and a mean duration of addiction of 2.47 years ± 1.37 years. Males constituted 83.2% of the patients, while females constituted 16.8%. The left femoral artery was affected more commonly than the right femoral artery, with an average of 75.6% and 24.4%, respectively. The most common presentation was bleeding from ruptured pseudoaneurysm (76.5%) and oozing with pulsatile mass (17.6%), while infected pulsatile swelling and misdiagnosis were uncommon. After surgical intervention, limb salvage was 95.8%, whereas mortality and amputation rate were 2.5 % and 1.7%, respectively. Conclusion The optimal management of femoral artery pseudoaneurysm in intravenous drug addicts is ligation and excision of the pseudoaneurysm without revascularization.

Architectural Distortion-Based Digital Mammograms Classification Using Depth Wise Convolutional Neural Network.

Architectural distortion is the third most suspicious appearance on a mammogram representing abnormal regions. Architectural distortion (AD) detection from mammograms is challenging due to its subtle and varying asymmetry on breast mass and small size. Automatic detection of abnormal ADs regions in mammograms using computer algorithms at initial stages could help radiologists and doctors. The architectural distortion star shapes ROIs detection, noise removal, and object location, affecting the classification performance, reducing accuracy. The computer vision-based technique automatically removes the noise and detects the location of objects from varying patterns. The current study investigated the gap to detect architectural distortion ROIs (region of interest) from mammograms using computer vision techniques. Proposed an automated computer-aided diagnostic system based on architectural distortion using computer vision and deep learning to predict breast cancer from digital mammograms. The proposed mammogram classification framework pertains to four steps such as image preprocessing, augmentation and image pixel-wise segmentation. Architectural distortion ROI's detection, training deep learning, and machine learning networks to classify AD's ROIs into malignant and benign classes. The proposed method has been evaluated on three databases, the PINUM, the CBIS-DDSM, and the DDSM mammogram images, using computer vision and depth-wise 2D V-net 64 convolutional neural networks and achieved 0.95, 0.97, and 0.98 accuracies, respectively. Experimental results reveal that our proposed method outperforms as compared with the ShuffelNet, MobileNet, SVM, K-NN, RF, and previous studies.

Management of Brachial Artery Pseudoaneurysms in Intravenous Drug Abusers.

Objective To determine the outcomes of the ligation and excision of brachial artery pseudoaneurysm in IV drug abusers without revascularization.  Methodology This retrospective observational study was conducted at the vascular surgery department Shaheed Muhtarma Benazir Bhutto trauma center Karachi from January 2019 to June 2020. All the patients with a history of intravenous drug abuse presented with pulsatile mass at or near cubital fossa, diagnosed as pseudoaneurysm, age ranging from 18-70 years, and of either gender were included in the study. Patients with pseudo-aneurysm secondary to trauma, hemodialysis, arteriovenous fistula, location other than cubital fossa, and whom primary revascularization was performed were excluded. The recorded data entered and analyzed using SPSS 20.0 (IBM Corp., Armonk, NY). Results A total of 20 intravenous drug addicts were included in the study. The mean age was of 31.10 ± 7.80 years, and the mean duration of addiction was 2.24 ± 1.16 years. The right arm is affected in almost two-thirds of patients. The most common presentation in the emergency department was ruptured pseudo-aneurysm with bleeding (65%), followed by oozing with pulsatile mass (30%), and infected pulsatile mass (5%). The outcome was Limb salvage (100%), and none of the patients had developed threatened ischemia of the arm or required amputation. Conclusion The ligation and excision of the pseudo-aneurysm, without revascularization, is a safe and effective treatment option for the management of pseudoaneurysm of the brachial artery secondary to intravenous drug addiction.

The Role of Polyphenol (Flavonoids) Compounds in the Treatment of Cancer Cells.

Cancer remains a second leading cause of deaths and major public health problem. It occurs due to extensive DNA damage caused by ultraviolet radiations, ionizing radiations, environmental agents, therapeutic agents, etc. Among all cancers, the most frequently diagnosed cancers are lung (12.7%), breast (10.9%), colorectal (9.7%), and gastric cancer (7.81%). Natural compounds are most favorable against cancer on the count of their anti-cancerous ability, easy to avail and efficient. Among natural compounds, polyphenols (flavonoids, catechin, hesperetin, flavones, quercetin, phenolic acids, ellagic acid, lignans, stilbenes, etc.) represent a large and diverse group used in the prevention and treatment of cancer. Natural flavonoids are derived from different plant sources and from various medicinal plants including Petroselinum crispum, Apium graveolens, Flemingia vestita, Phyllanthus emblica, etc. Natural flavonoids possess antioxidant, anti-inflammation, as well as anti-cancerous activities through multiple pathways, they induce apoptosis in breast, colorectal, and prostate cancers, lower the nucleoside diphosphate kinase-B activity in lung, bladder and colon cancers, inhibit cell-proliferation and cell cycle arrest by suppressing the NF-kB pathway in various cancers, etc. The current review summarized the anticancer activities of natural polyphenols and their mechanisms of action.

Quality of Colonoscopy and Spectrum of Lower Gastrointestinal Disease as Determined by Colonoscopy.

OBJECTIVE: To document the quality of colonoscopy practice and the pattern of colonic disease including polyp detection rate at Shifa International Hospital, Islamabad, Pakistan. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Shifa International Hospital, Islamabad, Pakistan, from May 2013 to June 2014. METHODOLOGY: This retrospective study recorded demographics of patients, indications and quality indices of 505 colonoscopies performed during the study period. Preparation was done with low residue diet and polyethylene glycol. Conscious sedation was generally used. Quality indices studied were compared with guideline standard. RESULTS: Out of 505 colonoscopy patients, 305 were males and 200 were females. The indications for colonoscopic examination were lower gastrointestinal bleeding (26.5%, n=134), screening for colorectal cancer (14.1%, n=71), chronic diarrhea (12.9%, n=65), abdominal pain (10.9%, n=55), anemia (9.1%, n=46), constipation (7.3%, n=37), hematochezia and diarrhea (6.3%, n=32), altered bowel habits (5.1%, n=26), weight loss (3.6%, n=18), colonic thickening on CT scan (3.0%, n=15) and others (1.2%, n=6). Bowel preparation was adequate (in 92%, n=465) cases. Cecal intubation rate was 88.71% (n=448). Endoscopic diagnoses were hemorrhoids (36.2%, n=183), normal (22%, n=111), polyps (11.3%, n=57), ulcerative colitis (8.7%, n=44), cancer (4%, n=20), diverticulosis (3.4%, n=17), infective colitis (2.6%, n=13), intestinal TB (2.6%, n=13), non-specific colitis (2.2%, n=11), proctitis (1.8%, n=9) and others (5.3%, n=27). CONCLUSION: There is room for improvement in quality of colonoscopy, cecal intubation rate is slightly below the recommended standard and polyp detection rate is quite low however, it is not clear if the low rate of polyp detection is due to missed lesions or low population incidence. Time to reach caecum and withdrawal time should clearly be documented in the notes which can help to evaluate quality of the procedure in a better way.