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High throughput proteomic and metabolic profiling identified target correction of metabolic abnormalities as a novel therapeutic approach in head and neck paraganglioma.

Transl Oncol 2021 Jun 9;14(8):101146. Epub 2021 Jun 9.

Department of Otolaryngology Head & Neck Surgery, The Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, No. 639, Zhi-Zao-Ju Road, Shanghai 200011, China; Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. Electronic address:

Head and neck paragangliomas (HNPGLs) are rare neoplasms that represent difficult treatment paradigms in neurotology. Germline mutations in genes encoding succinate dehydrogenase (SDH) are the cause of nearly all familial HNPGLs. However, the molecular mechanisms underlying tumorigenesis remain unclear. Read More

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Verification of the critical-care pain observation tool in conscious patients with hemiparesis or cognitive dysfunction.

J Crit Care 2021 Jun 9;65:91-97. Epub 2021 Jun 9.

Department of Neurosurgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University, Taiwan; PhD Program of Biomedical Engineering, Chang Gung University, Taiwan. Electronic address:

Purpose: Altered cognition or hemiparesis can occur in neurocritical but conscious patients, and recognizing pain is challenging. This study aimed to test the reliability and validity of the Critical-Care Pain Observation Tool (CPOT) in this specific group.

Materials And Methods: This prospective study included ventilated, conscious patients who had certain neurologic deficits. Read More

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Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): a multi-cohort, open-label, registrational, phase 1/2 study.

Lancet Diabetes Endocrinol 2021 Jun 9. Epub 2021 Jun 9.

Earle A Chiles Research Institute, Providence Portland Medical Center, Portland, OR, USA.

Background: Oncogenic alterations in RET represent important therapeutic targets in thyroid cancer. We aimed to assess the safety and antitumour activity of pralsetinib, a highly potent, selective RET inhibitor, in patients with RET-altered thyroid cancers.

Methods: ARROW, a phase 1/2, open-label study done in 13 countries across 71 sites in community and hospital settings, enrolled patients 18 years or older with RET-altered locally advanced or metastatic solid tumours, including RET-mutant medullary thyroid and RET fusion-positive thyroid cancers, and an Eastern Co-operative Oncology Group performance status of 0-2 (later limited to 0-1 in a protocol amendment). Read More

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Initial experience of endoscopic ultrasound-guided antegrade covered stent placement with long duodenal extension for malignant distal biliary obstruction (with video).

J Hepatobiliary Pancreat Sci 2021 Jun 12. Epub 2021 Jun 12.

Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.

Background/purpose: This study aimed to evaluate the feasibility of endoscopic ultrasound (EUS)-guided antegrade covered stent placement with long duodenal extension (EASL) for malignant distal biliary obstruction (MDBO) with duodenal obstruction (DO) or surgically altered anatomy (SAA) after failed endoscopic retrograde cholangiopancreatography (ERCP).

Methods: Outcomes were technical and clinical success, reintervention rate, adverse events, stent patency, and overall survival. Inverse probability of treatment weighting (IPTW) and competing-risk analysis were performed to compare with conventional EUS-BD. Read More

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A hungry Histiocyte, altered immunity and myriad of problems: Diagnostic challenges for Pediatric HLH.

Int J Lab Hematol 2021 Jun 12. Epub 2021 Jun 12.

Division of Pediatric Hematology/Oncology, Department of Pediatrics, VMMC and Safdarjung Hospital, New Delhi, India.

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is an immune deregulation disorder with varied clinical presentation which clinically overlaps with widespread tropical infections.

Methods: We conducted a retrospective chart review of children diagnosed with HLH at our center from February-2017 to October-2020.

Results: Out of the nine diagnosed patients, genetic predisposition was present in three children; two had identified infectious triggers. Read More

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Cortical Responses to Vowel Sequences in Awake and Anesthetized States: A Human Intracranial Electrophysiology Study.

Cereb Cortex 2021 Jun 12. Epub 2021 Jun 12.

Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.

Elucidating neural signatures of sensory processing across consciousness states is a major focus in neuroscience. Noninvasive human studies using the general anesthetic propofol reveal differential effects on auditory cortical activity, with a greater impact on nonprimary and auditory-related areas than primary auditory cortex. This study used intracranial electroencephalography to examine cortical responses to vowel sequences during induction of general anesthesia with propofol. Read More

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The Relationship Between Frontal QRS-T Angle and the Severity of Newly Diagnosed Chronic Obstructive Pulmonary Disease.

Int J Clin Pract 2021 Jun 12:e14500. Epub 2021 Jun 12.

Department of Cardiology, Faculty of Medicine, Harran University, Sanliurfa, Turkey.

Background: Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent airflow restriction and respiratory symptoms. Studies demonstrated that cardiac arrhythmias and cardiovascular mortality increased in these patients due to altered myocardial repolarization. Frontal QRS-T angle is a novel marker of myocardial depolarization and repolarization heterogeneity. Read More

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Hepatic drug-metabolizing enzymes and drug transporters in Wilson's disease patients with liver failure.

Pharmacol Rep 2021 Jun 11. Epub 2021 Jun 11.

Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Al. Powstańców Wlkp. 72, 70-111, Szczecin, Poland.

Background: Wilson's disease is a genetic disorder inherited in a recessive manner, caused by mutations in the copper-transporter ATP7B. Although it is a well-known disease, currently available treatments are far from satisfactory and their efficacy varies in individual patients. Due to the lack of information about drug-metabolizing enzymes and drug transporters profile in Wilson's disease livers, we aimed to evaluate the mRNA expression and protein abundance of selected enzymes and drug transporters in this liver disorder. Read More

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Mortalin/glucose-regulated protein 75 promotes the cisplatin-resistance of gastric cancer via regulating anti-oxidation/apoptosis and metabolic reprogramming.

Cell Death Discov 2021 Jun 11;7(1):140. Epub 2021 Jun 11.

Department of General Surgery, The Affiliated Changzhou No. 2 Hospital of Nanjing Medical University, Changzhou, China.

Platinum drug treatment is one of the most predominant chemotherapeutic strategies for patients with gastric cancer (GC). However, the therapeutic effect is less than satisfactory, largely due to the acquired resistance to platinum drugs. Therefore, a better understanding of the underlying mechanisms can greatly improve the therapeutic efficacy of GC. Read More

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Mucosal Invariant T cells are Diminished in Very Early-Onset Inflammatory Bowel Disease.

J Pediatr Gastroenterol Nutr 2021 Jun 7. Epub 2021 Jun 7.

Division of Allergy Immunology, Children's Hospital of Philadelphia, Philadelphia, PA 19104 USA Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA 19104 USA.

Objectives: Very early-onset inflammatory bowel disease arises in children less than six years old, a critical time for immunologic development and maturation of the intestinal microbiome. Non-conventional lymphocytes, defined here as mucosal-associated invariant T cells and innate lymphocytes, require microbial products for either development or expansion, aspects that could be altered in very early-onset inflammatory bowel disease. Our objective was to define conventional leukocyte and non-conventional lymphocyte populations in controls and patients using multiparameter flow cytometry to test the hypothesis that their frequencies would be altered in a chronic inflammatory state associated with significant dysbiosis. Read More

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Diagnostic Accuracy and Failure Mode Analysis of a Deep Learning Algorithm for the Detection of Cervical Spine Fractures.

AJNR Am J Neuroradiol 2021 Jun 11. Epub 2021 Jun 11.

Department of Radiology (M.E.L., J.W.G., J.-P.J.Y.), University of Wisconsin-Madison, Madison, Wisconsin

Background And Purpose: Artificial intelligence decision support systems are a rapidly growing class of tools to help manage ever-increasing imaging volumes. The aim of this study was to evaluate the performance of an artificial intelligence decision support system, Aidoc, for the detection of cervical spinal fractures on noncontrast cervical spine CT scans and to conduct a failure mode analysis to identify areas of poor performance.

Materials And Methods: This retrospective study included 1904 emergent noncontrast cervical spine CT scans of adult patients (60 [SD, 22] years, 50. Read More

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Lifetime smoking history and cohort-based smoking prevalence in chronic pancreatitis.

Pancreatology 2021 May 29. Epub 2021 May 29.

Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Background/objective: Smoking prevalence in patients with chronic pancreatitis [CP] is high. We aimed to understand lifetime history of smoking and cohort trends in CP patients to inform effective strategies for smoking cessation.

Method: Data on 317 CP patients from the North American Pancreatitis Study 2 [NAPS2] Continuation and Validation Study and the NAPS2 Ancillary Study were analyzed. Read More

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Altered neuroaxonal integrity in schizophrenia and major depressive disorder assessed with neurofilament light chain in serum.

J Psychiatr Res 2021 Jun 2;140:141-148. Epub 2021 Jun 2.

Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric University Hospital Zürich, University of Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich and Swiss Federal Institute of Technology Zurich, Zurich, Switzerland.

Background: Schizophrenia (SZ) and major depressive disorders (MDD) have been frequently linked to anatomical brain alterations. However, the relationship between brain pathology, inflammation and clinical symptoms in these disorders is still unclear. Thus, by applying novel blood markers of neuroaxonal integrity such as neurofilament light chain (NfL), we can now address main issues in psychiatric research and potentially offer innovative diagnostic tools toward better clinical characterizations and monitoring in both SZ and MDD. Read More

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Changes in kinematics, kinetics, and muscle activity in patients with lumbar spinal stenosis during gait: systematic review.

Spine J 2021 Jun 8. Epub 2021 Jun 8.

Department of Orthopaedic Surgery, University of Arkansas for Medical Science, Little Rock, AR; Mechanical and Biomedical Engineering Department, College of Engineering, Boise State University, Boise, ID.

Background Context: Lumbar spinal stenosis (LSS) is one of the most common orthopaedic conditions and affects more than half a million people over the age of 65 in the US. Patients with LSS have gait dysfunction and movement deficits due to pain and symptoms caused by compression of the nerve roots within a narrowed spinal canal.

Purpose: The purpose of the current systematic review was to summarize existing literature reporting biomechanical changes in gait function that occur with LSS, and identify knowledge gaps that merit future investigation in this important patient population. Read More

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Altered spontaneous cortical activity in mild glaucoma: A quantitative EEG study.

Neurosci Lett 2021 Jun 8:136036. Epub 2021 Jun 8.

Stress and cognitive electroimaging laboratory, Department of Physiology, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

Functional neuroimaging studies have reported alterations in cortical activity indicating glaucoma as a progressive neurodegenerative disease. Hence the current study aimed to assess the cortical activity using high-density EEG in patients with mild glaucoma during resting state. Treatment-naive 37 patients with primary open angle glaucoma (POAG), 34 patients with primary angle closure glaucoma (PACG), and 32 healthy controls were included in the study. Read More

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Structural white matter alterations in carpal tunnel syndrome: A modified TBSS study.

Brain Res 2021 Jun 8:147558. Epub 2021 Jun 8.

School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Center of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. Electronic address:

Functional and structural brain alterations have been noted in carpal tunnel syndrome (CTS), the most common entrapment peripheral neuropathy. Previous studies were mainly focused on somatosensory cortices. However, the changes of white matter diffusion properties in nonsensorimotor cortices remain uninvestigated. Read More

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Metabolic changes in synovial cells in early inflammation: Involvement of CREB phosphorylation in the anti-inflammatory effect of 2-deoxyglucose.

Arch Biochem Biophys 2021 Jun 8:108962. Epub 2021 Jun 8.

Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

The involvement of metabolic reprogramming has been suggested to contribute to the pathophysiology of rheumatoid arthritis (RA). Glycolysis is enhanced in synovial cell metabolism in RA patients. Inhibitors of glycolysis are known to have anti-inflammatory effects. Read More

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Persistent visual dysfunction following PRES due to COVID-19: Case series and literature review.

Eur J Neurol 2021 Jun 11. Epub 2021 Jun 11.

Department of Ophthalmology, Colorado University School of Medicine, 1675 North Aurora Ct. F731, Aurora, CO, 80045, USA.

Background: The full spectrum of neurological sequelae in COVID-19 is beginning to emerge. SARS-CoV-2 has the potential to cause both direct and indirect brain vascular endothelial damage through infection and inflammation that may result in long-term neurological signs and symptoms. We sought to illuminate persistent neuro-ophthalmological deficits that may be seen following posterior reversible encephalopathy syndrome (PRES) due to COVID-19. Read More

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The Impact of Obesity on Critical Illnesses.

Shock 2021 Jun 10. Epub 2021 Jun 10.

Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Department of Pediatric Critical Care, Tel-Aviv, Israel Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Abstract: In the last few decades, obesity became one of the world's greatest health challenges reaching a size of global epidemic in virtually all socioeconomic statuses and all age groups. Obesity is a risk factor for many health problems and as its prevalence gradually increases is becoming a significant economic and health burden. In this manuscript we describe how normal respiratory and cardiovascular physiology is altered by obesity. Read More

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Gait Adaptations at 8 Years After Reconstruction of Unilateral Isolated and Combined Posterior Cruciate Ligament Injuries.

Am J Sports Med 2021 Jun 11:3635465211017147. Epub 2021 Jun 11.

Julius Wolff Institute, Berlin Institute of Health and Charité-Universitätsmedizin Berlin, Berlin, Germany.

Background: It remains unclear how posterior cruciate ligament (PCL) reconstruction influences long-term lower extremity joint biomechanics.

Purpose: To determine whether patients who underwent PCL reconstruction exhibited long-term alterations in lower limb gait mechanics.

Study Design: Controlled laboratory study. Read More

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Survival motor neuron deficiency slows myoblast fusion through reduced myomaker and myomixer expression.

J Cachexia Sarcopenia Muscle 2021 Jun 11. Epub 2021 Jun 11.

Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, Bethesda, MD, USA.

Background: Spinal muscular atrophy is an inherited neurodegenerative disease caused by insufficient levels of the survival motor neuron (SMN) protein. Recently approved treatments aimed at increasing SMN protein levels have dramatically improved patient survival and have altered the disease landscape. While restoring SMN levels slows motor neuron loss, many patients continue to have smaller muscles and do not achieve normal motor milestones. Read More

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The Effects of Limosilactobacillus reuteri LR-99 Supplementation on Body Mass Index, Social Communication, Fine Motor Function, and Gut Microbiome Composition in Individuals with Prader-Willi Syndrome: a Randomized Double-Blinded Placebo-Controlled Trial.

Probiotics Antimicrob Proteins 2021 Jun 11. Epub 2021 Jun 11.

The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

Prader-Willi syndrome (PWS) is a rare genetic disorder associated with developmental delay, obesity, and neuropsychiatric comorbidities. Limosilactobacillus reuteri (Lactobacillus reuteri, Lact. reuteri) has demonstrated anti-obesity and anti-inflammatory effects in previous studies. Read More

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Characterizing the Impact of COVID-19 on Pre-Exposure Prophylaxis (PrEP) Care.

AIDS Behav 2021 Jun 10. Epub 2021 Jun 10.

Department of Medicine, Infectious Diseases, The Miriam Hospital, 14 Third Street, Providence, RI, 02906, USA.

COVID-19 is a public health crisis that has fundamentally altered health care provision. The purpose of this study was to examine the impact of COVID-19 on pre-exposure prophylaxis (PrEP) care. We reviewed all patient records for those who presented for PrEP care at a PrEP program in Providence, Rhode Island from September 1st, 2019 to May 29th, 2020. Read More

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Novel Immune Cell Subsets Exhibit Different Associations With Vascular Outcomes in Chronic Kidney Disease Patients-Identifying Potential Biomarkers.

Front Med (Lausanne) 2021 25;8:618286. Epub 2021 May 25.

Bone and Mineral Research Unit, Hospital Universitario Central de Asturias, Oviedo, Spain.

Alterations in novel immune cell subsets, such as angiogenic T cells (Tang), senescent T cells (CD4CD28), and monocyte subsets are associated with impaired vascular homeostasis in several inflammatory conditions. However, mediators underlying vascular deterioration in chronic kidney disease (CKD) are poorly characterized. This study assessed their role in the vascular deterioration of CKD using a broad spectrum of surrogate markers ranging from altered functionality to overt calcification. Read More

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Post-Transformation IGHV-IGHD-IGHJ Mutations in Chronic Lymphocytic Leukemia B Cells: Implications for Mutational Mechanisms and Impact on Clinical Course.

Front Oncol 2021 25;11:640731. Epub 2021 May 25.

The Feinstein Institutes for Medical Research, Institute for Molecular Medicine, Northwell Health, Manhasset, NY, United States.

Analyses of IGHV gene mutations in chronic lymphocytic leukemia (CLL) have had a major impact on the prognostication and treatment of this disease. A hallmark of IGHV-mutation status is that it very rarely changes clonally over time. Nevertheless, targeted and deep DNA sequencing of IGHV-IGHD-IGHJ regions has revealed intraclonal heterogeneity. Read More

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Methadone Toxicity in a Pediatric Patient: A Case Report.

Cureus 2021 May 5;13(5):e14860. Epub 2021 May 5.

Pediatrics, Woodhull Medical Center, New York, USA.

Pediatric morbidity and mortality associated with methadone poisoning have been rising over the years. In this report, we discuss a case of a four-year-old boy who presented with respiratory distress and a depressed level of consciousness. A urine drug testing was performed given the miosis along with the depressed level of consciousness; the test was found to be positive for methadone, and no other cause of drowsiness was identified. Read More

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Clinical Impact of Reporting Coronary Artery Calcium Scores of Non-Gated Chest Computed Tomography on Statin Management.

Cureus 2021 May 5;13(5):e14856. Epub 2021 May 5.

Radiology, Brookwood Baptist Medical Center, Birmingham, USA.

Introduction Coronary artery calcium (CAC) scoring is used as a screening tool for patients with intermediate 10-year arteriosclerotic cardiovascular disease (ASCVD) risk. Results obtained on non-contrast non-gated chest CT (ngCCT) correlate well to those obtained on gated CTs. This paper aims to determine how the routine reporting of CAC scores on ngCCT scans with ASCVD risk of less than 12. Read More

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Screening for Sarcopenia (Physical Frailty) in the COVID-19 Era.

Int J Endocrinol 2021 21;2021:5563960. Epub 2021 May 21.

Department of Psychiatry, Teikyo University School of Medicine, Tokyo, Japan.

Although the numbers of aged populations have risen considerably in the last few decades, the current coronavirus disease 2019 (COVID-19) has revealed an extensive vulnerability among these populations. Sarcopenia is an age-related disorder that increases hospitalization, dependencies, and mortality in older adults. It starts to develop in midlife or even earlier as a result of unbalanced diet/poor nutrition and low levels of physical activity, in addition to chronic disorders such as obesity and diabetes mellitus. Read More

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Microbiota and Microglia Interactions in ASD.

Front Immunol 2021 25;12:676255. Epub 2021 May 25.

Department of Physiology and Pharmacology, Snyder Institute of Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Autism spectrum disorders (ASD) are serious, highly variable neurodevelopmental disorders, commonly characterized by the manifestation of specific behavioral abnormalities, such as stereotypic behaviors and deficits in social skills, including communication. Although the neurobiological basis for ASD has attracted attention in recent decades, the role of microglial cells, which are the main resident myeloid cell population in the brain, is still controversial and underexplored. Microglia play several fundamental roles in orchestrating brain development and homeostasis. Read More

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Altered Immune Phenotypes and Gene Variation in Multiple Sclerosis Patients Failing Interferon Treatment.

Front Immunol 2021 25;12:628375. Epub 2021 May 25.

Cytokine Signaling Unit, Department of Immunology, Institut Pasteur, Paris, France.

Background: Interferon beta (IFN) has been prescribed as a first-line disease-modifying therapy for relapsing-remitting multiple sclerosis (RRMS) for nearly three decades. However, there is still a lack of treatment response markers that correlate with the clinical outcome of patients.

Aim: To determine a combination of cellular and molecular blood signatures associated with the efficacy of IFN treatment using an integrated approach. Read More

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