Rare co-occurrence of probable pernicious anemia and autoimmune hepatitis in a 55-year-old male patient: A case report.

This is a case of probable pernicious anemia in the setting of autoimmune hepatitis. A 55-year-old male patient presented to the Emergency Room at Dr. Ruth K.

The role of hydrogels in the management of brain tumours: a narrative review.

Conventional therapeutic techniques for brain tumours have limitations and side effects, necessitating the need for alternative treatment options. MRI-monitored therapeutic hydrogel systems show potential as a non-surgical approach for brain tumour treatment. Hydrogels have unique physical and chemical properties that make them promising for brain tumour treatment, including the ability to encapsulate therapeutic agents, provide sustained and controlled drug release, and overcome the blood-brain barrier for better penetration.

Evidence of a Hardening in the Cosmic Ray Proton Spectrum at around 166 TeV Observed by the GRAPES-3 Experiment.

We present the measurement of the cosmic ray proton spectrum from 50 TeV to 1.3 PeV using 7.81×10^{6} extensive air shower events recorded by the ground-based GRAPES-3 experiment between 1 January 2014 and 26 October 2015 with a live time of 460 day.

Exploring switch II pocket conformation of KRAS(G12D) with mutant-selective monobody inhibitors.

The G12D mutation is among the most common KRAS mutations associated with cancer, in particular, pancreatic cancer. Here, we have developed monobodies, small synthetic binding proteins, that are selective to KRAS(G12D) over KRAS(wild type) and other oncogenic KRAS mutations, as well as over the G12D mutation in HRAS and NRAS. Crystallographic studies revealed that, similar to other KRAS mutant-selective inhibitors, the initial monobody bound to the S-II pocket, the groove between switch II and α3 helix, and captured this pocket in the most widely open form reported to date.

Inhibition of RAS-driven signaling and tumorigenesis with a pan-RAS monobody targeting the Switch I/II pocket.

RAS mutants are major therapeutic targets in oncology with few efficacious direct inhibitors available. The identification of a shallow pocket near the Switch II region on RAS has led to the development of small-molecule drugs that target this site and inhibit KRAS(G12C) and KRAS(G12D). To discover other regions on RAS that may be targeted for inhibition, we have employed small synthetic binding proteins termed monobodies that have a strong propensity to bind to functional sites on a target protein.

Development and evaluation of herbal formulation AKIGTU01 and AKIGCL03 against acne producing microbes.

Acne vulgaris is a common global skin disease affecting teenagers and adults and exerting serious psychological impacts which includes everlasting scarring, reduced self-image, depression and anxiety. One of the suspected causative agent of acne is Propionibacterium acnes; a Gram positive anaerobic organism which lives in skin hair follicle and openings. Treatments currently available for acne include use of oral antibiotics, hormones, isotretinoin and also physical treatments like lesion removal and photo-therapy.

Analysis of temporal changes in HIV-1 CRF01_AE gag genetic variability and CD8 T-cell epitope evolution.

Currently, little is known about the time-dependent evolution of human immunodeficiency virus-1 (HIV-1) circulating recombinant forms (CRF) 01_AE, a dominant recombinant form associated with HIV-1 epidemics worldwide. Since gag is a highly immunodominant HIV-1 protein, we performed a comparative analysis of the CRF01_AE gag protein's time-dependent changes and evolution. A total of 3105 HIV-1 CRF01_AE gag sequences representing 17 countries from the timeline 1990-2017 were obtained.

Identification of the nucleotide-free state as a therapeutic vulnerability for inhibition of selected oncogenic RAS mutants.

RAS guanosine triphosphatases (GTPases) are mutated in nearly 20% of human tumors, making them an attractive therapeutic target. Following our discovery that nucleotide-free RAS (apo RAS) regulates cell signaling, we selectively target this state as an approach to inhibit RAS function. Here, we describe the R15 monobody that exclusively binds the apo state of all three RAS isoforms in vitro, regardless of the mutation status, and captures RAS in the apo state in cells.

The impact of regionality and hospital status on mortality associated with non-accidental trauma.

Introduction: Non-accidental trauma (NAT) affects 2 per 100,000 children annually in the US and may go unrecognized. The aim of this study to quantify the burden of NAT and to evaluate regional variations in mortality.

Methods: The Kids Inpatient Database (2000-2012) was queried for pediatric patients presenting with a diagnosis of NAT.

Targeting the KRAS α4-α5 allosteric interface inhibits pancreatic cancer tumorigenesis.

is the most frequently mutated oncogene in human cancer with nearly ~20% of cancer patients possessing mutations in one of three genes ( or ). However, is mutated in nearly 90% of pancreatic ductal carcinomas (PDAC). Although pharmacological inhibition of RAS has been challenging, KRAS(G12C)-specific inhibitors have recently entered the clinic.

Epigenetic Silencing of and Genes by CpG Island Hypermethylation in Epithelial Ovarian Cancer Patients.

Transcriptional silencing induced by hypermethylation of CpG islands in the promoter regions of genes is believed to be an important mechanism of carcinogenesis in human cancers including epithelial ovarian cancer (EOC). Previously published data on gene methylation of EOC focused mainly on single gene or on cancer tissues. Objectives of the study were to estimate the promoter hypermethylation status of and genes in circulating blood of EOC patients and to determine their association with clinicopathological features of EOC.

Should I be Concerned? Surgical Training in the Time of COVID19.

As the US healthcare system restructured to deal with the COVID-19 pandemic, medical training was significantly disrupted. During the peak of the crisis, three surgical trainees in different stages of their residency shared their experiences and concerns on how this pandemic affected their training. The article is intended to generate discussion on the concerns of derailment and stagnation of surgical training and difficulties faced at all levels of surgical training to perform clinical duties and fulfill academic responsibilities during the early months of the COVID pandemic.

Inhibition of RAS: proven and potential vulnerabilities.

RAS is a membrane localized small GTPase frequently mutated in human cancer. As such, RAS has been a focal target for developing cancer therapeutics since its discovery nearly four decades ago. However, efforts to directly target RAS have been challenging due to the apparent lack of readily discernable deep pockets for binding small molecule inhibitors leading many to consider RAS as undruggable.

Correction to: Ectopic PD-L1 expression in JAK2 (V617F) myeloproliferative neoplasm patients is mediated via increased activation of STAT3 and STAT5.

In the original publication, third author name was incorrectly published as "Ab Rashid Mir". The correct name should read as "Rashid Mir".

Hypotension after intensive care unit drop-off in adult cardiac surgery patients.

Background: Hypotension is a frequent complication in the intensive care unit (ICU) after adult cardiac surgery.

Aim: To describe frequency of hypotension in the ICU following adult cardiac surgery and its relation to the hospital outcomes.

Methods: A retrospective study of post-cardiac adult surgical patients at a tertiary academic medical center in a two-year period.

Ectopic PD-L1 expression in JAK2 (V617F) myeloproliferative neoplasm patients is mediated via increased activation of STAT3 and STAT5.

Escalated PD-L1 expression has been identified during malignant transformation in a number of cancer types and helps cancer cells escape an effective anti-tumor immune response. The mechanisms underlying escalated production of PD-L1 in many cancers, however, are still far from clear. We studied PD-L1, STAT3 and STAT5 mRNA expression using qRT-PCR in 72 BCR/ABL1 negative myeloproliferative neoplasm (MPN) patients (39 polycythemia vera and 33 essential thrombocythemia).

Direct and residual impacts of zeolite on the remediation of harmful elements in multiple contaminated soils using cabbage in rotation with corn.

In the present work, in-situ two pot trials were conducted to explore the direct and residual influences of zeolite (ZL) on plant height, dry biomass and bioavailability of Pb, Cd, Cu, and Zn by growing cabbage followed by corn in goldmine-contaminated (GM-C), smelter factory-contaminated (SF-C), and farmland-contaminated (FL-C) soils. Initially, a single treatment of ZL was applied at 20 t/ha, and cabbage was grown under greenhouse pot conditions. After cabbage harvesting, corn was grown in the same pots without additional application of ZL.

Defining the Burden of Emergency General Surgery in Transplant Patients: A Nationwide Examination.

Background: Transplant patients are at the risk of serious sequelae from medical and surgical intervention. The incidence and burden of emergency general surgery (EGS) in transplant patients are scarcely known. This study aims to identify predictors of outcomes in transplant patients with EGS needs.

Gaps in access to comprehensive rehabilitation following traumatic injuries in children: A nationwide examination.

Introduction: Acute rehabilitation following traumatic injuries is associated with improved functional recovery. Access is often limited to patients at the time of hospital discharge. This phenomenon remains less well described in children, who may have more to benefit with rehabilitation posttrauma.

Undifferentiated Shock and Extreme Elevation of Procalcitonin Related to Kratom Use.

An 18-year-old male with history of polysubstance abuse presented to the emergency department with intractable vomiting, diarrhea, and abdominal pain for one day after the consumption of kratom. Examination revealed arterial hypotension, tachycardia, and prolonged capillary refill. Laboratory studies showed white blood cell count (WBC) of 23.

Measurement of the Electrical Properties of a Thundercloud Through Muon Imaging by the GRAPES-3 Experiment.

The GRAPES-3 muon telescope located in Ooty, India records rapid (∼10  min) variations in the muon intensity during major thunderstorms. Out of a total of 184 thunderstorms recorded during the interval of April 2011-December 2014, the one on December 1, 2014 produced a massive potential of 1.3 GV.

The Promising Signatures of Circulating microRNA-145 in Epithelial Ovarian Cancer Patients.

Background: Epithelial ovarian cancer continues to be a deleterious threat to women as it is asymptomatic and is typically detected in advanced stages. Cogent non-invasive biomarkers are therefore needed which are effective in apprehending the disease in early stages. Recently, miRNA deregulation has shown a promising magnitude in ovarian cancer tumorigenesis.

Correlation Between Oxygen Saturation and Pulse Tracing Patterns on Overnight Oximetry With Normal Desaturation Index Is an Independent Predictor of Obstructive Sleep Apnea.

Study Objectives: Overnight pulse oximetry (OPO) is commonly used as a screening test for obstructive sleep apnea. Heart rate variability (HRV) correlates well with apnea-hypopnea index during polysomnography (PSG). We hypothesized that visual correlation of episodic increase in HRV with minimal oxygen desaturations on normal OPO (oxygen desaturation index less than 5 events/h) is predictive of OSA.

Association of GABAA Receptor Gene with Epilepsy Syndromes.

GABA has always been an inviting target in the etiology and treatment of epilepsy. The GABRA1, GABRG2, and GABRD genes provide instructions for making α1, ϒ2, and δ subunits of GABAA receptor protein respectively. GABAA is considered as one of the most important proteins and has found to play an important role in many neurological disorders.