Mechanism of enhancing chemotherapy efficacy in pancreatic ductal adenocarcinoma with paricalcitol and hydroxychloroquine.

Pancreatic ductal adenocarcinoma (PDAC) has a minimal (<15%) 5-year existence, in part due to resistance to chemoradiotherapy. Previous research reveals the impact of paricalcitol (P) and hydroxychloroquine (H) on altering the lysosomal fusion, decreasing stromal burden, and triggering PDAC to chemotherapies. This investigation aims to elucidate the molecular properties of the H and P combination and their potential in sensitizing PDAC to gemcitabine (G).

A Pan-RAS Inhibitor with a Unique Mechanism of Action Blocks Tumor Growth and Induces Antitumor Immunity in Gastrointestinal Cancer.

RAS is a common driver of cancer that was considered undruggable for decades. Recent advances have enabled the development of RAS inhibitors, but the efficacy of these inhibitors remains limited by resistance. Here, we developed a pan-RAS inhibitor, ADT-007, that binds nucleotide-free RAS to block GTP activation of effector interactions and MAPK/AKT signaling, resulting in mitotic arrest and apoptosis.

Spatial transcriptomic analysis of primary and metastatic pancreatic cancers highlights tumor microenvironmental heterogeneity.

Although the spatial, cellular and molecular landscapes of resected pancreatic ductal adenocarcinoma (PDAC) are well documented, the characteristics of its metastatic ecology remain elusive. By applying spatially resolved transcriptomics to matched primary and metastatic PDAC samples, we discovered a conserved continuum of fibrotic, metabolic and immunosuppressive spatial ecotypes across anatomical regions. We observed spatial tumor microenvironment heterogeneity spanning beyond that previously appreciated in PDAC.

Technical Aspects and Outcome of Multi-Staged and Single-Staged Thoracoabdominal Fenestrated Endovascular Aortic Repair.

Purpose: In some cases of endovascular thoracoabdominal or juxtarenal aortic aneurysm repair, a thoracic endograft in combination with a fenestrated renovisceral device may be needed in order to create a sufficient proximal landing zone. This study aimed to evaluate the technical aspects and postoperative morbidity of a single- or 2-stage approach.

Methods: Eighty-seven consecutive patients undergoing thoracic endovascular aortic repair (TEVAR) in combination with elective fenestrated repair (fenestrated endovascular aortic repair [FEVAR]; fenestrated Anaconda device) from 2015 to 2022 were included in this retrospective bicentric study.

Mitochondrial respiration in peripheral arterial disease depends on stage severity.

Peripheral arterial disease (PAD) is an increasing cause of morbidity and its severity is graded based on clinical manifestation. To investigate the influence of the different stages on myopathy of ischemic muscle we analysed severity-dependent effects of mitochondrial respiration in PAD. Eighteen patients with severe PAD, defined as chronic limb-threatening ischemia, 47 patients with intermittent claudication (IC) and 22 non-ischemic controls were analysed.

Assessment of clinical chemistry and hematological parameters in female Sprague-Dawley rats following a 7-day oral exposure to three different species of .

has grown in popularity due to its broad therapeutic benefits. Despite its popularity, comprehensive safety evaluations for three medicinal species are limited. In this study, female Sprague-Dawley rats received oral doses (0, 25, 50, 100, 200 mg/kg/d) of 75% (v/v) ethanol extract from the aerial parts of 9 samples of three species - , , and - over a 7-day period.

A Novel Pan-RAS Inhibitor with a Unique Mechanism of Action Blocks Tumor Growth in Mouse Models of GI Cancer.

Unlabelled: Here, we describe a novel pan-RAS inhibitor, ADT-007, that potently inhibited the growth of RAS mutant cancer cells irrespective of the RAS mutation or isozyme. RAS cancer cells with GTP-activated RAS from upstream mutations were equally sensitive. Conversely, RAS cancer cells harboring downstream BRAF mutations and normal cells were essentially insensitive to ADT-007.

Historical visit attendance as predictor of treatment interruption in South African HIV patients: Extension of a validated machine learning model.

Retention of antiretroviral (ART) patients is a priority for achieving HIV epidemic control in South Africa. While machine-learning methods are being increasingly utilised to identify high risk populations for suboptimal HIV service utilisation, they are limited in terms of explaining relationships between predictors. To further understand these relationships, we implemented machine learning methods optimised for predictive power and traditional statistical methods.

A Modified Run-Off Resistance Score from Cross-Sectional Imaging Discriminates Chronic Critical Limb Ischemia from Intermittent Claudication in Peripheral Arterial Disease.

Atherosclerotic peripheral arterial disease (PAD) leads to intermittent claudication (IC) and may progress into chronic limb-threatening ischemia (CLTI). Scoring systems to determine the atherosclerotic burden of a diseased extremity have been developed. This study aimed to evaluate a modification of the run-off resistance (mROR) score for its usability in cross-sectional imaging.

[Functional results and complications in the long-term follow-up after 25-gauge vitrectomy of epiretinal membrane].

Background: Idiopathic epiretinal membranes can lead, among other things, to visual impairment and metamorphopsia. The treatment of choice is a pars plana vitrectomy with removal of the membrane. The improvement of visual acuity and postoperative complications have already been described in several studies.

Validation and Improvement of a Machine Learning Model to Predict Interruptions in Antiretroviral Treatment in South Africa.

Introduction: Machine learning algorithms are increasingly being used to inform HIV prevention and detection strategies. We validated and extended a previously developed machine learning model for patient retention on antiretroviral therapy in a new geographic catchment area in South Africa.

Methods: We compared the ability of an adaptive boosting algorithm to predict interruption in treatment (IIT) in 2 South African cohorts from the Free State and Mpumalanga and Gauteng and North West (GA/NW) provinces.

Recovery from Beak and Feather Disease Virus Infection in a Cape Parrot (Poicephalus robustus) Population in South Africa.

Psittacine beak and feather disease (PBFD) is one of the most important viral diseases affecting parrot species worldwide. Outbreaks of PBFD have been reported in wild endemic and endangered South African Cape Parrots (Poicephalus robustus), most recently in 2008. A previous study of wild Cape Parrots in the Eastern Cape region of South Africa in 2010-11 found 34/49 birds positive for beak and feather disease virus (BFDV), the causative agent of PBFD, showing that the outbreak was still ongoing.

Surface-to-space atmospheric waves from Hunga Tonga-Hunga Ha'apai eruption.

The January 2022 Hunga Tonga-Hunga Ha'apai eruption was one of the most explosive volcanic events of the modern era, producing a vertical plume that peaked more than 50 km above the Earth. The initial explosion and subsequent plume triggered atmospheric waves that propagated around the world multiple times. A global-scale wave response of this magnitude from a single source has not previously been observed.

[SGLT2 inhibitorsfor treatment of chronic kidney disease without diabetes or heart failure].

This review summarises the current knowledge of electroconvulsive therapy (ECT) which is still the most potent and fast-acting antidepressant intervention. The modern procedure is safe when general precautions are taken. Cognitive side effects are transient in most patients, and concerns about side effects should not prevent relevant use.

Identification of Functional Heterogeneity of Carcinoma-Associated Fibroblasts with Distinct IL6-Mediated Therapy Resistance in Pancreatic Cancer.

Unlabelled: The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) involves a significant accumulation of fibroblasts as part of the host response to cancer. Using single-cell RNA sequencing, multiplex immunostaining, and several genetic mouse models, we identify carcinoma-associated fibroblasts (CAF) with opposing functions in PDAC progression. Depletion of fibroblast activation protein (FAP)+ CAFs results in increased survival, in contrast to depletion of alpha smooth muscle actin (αSMA)+ CAFs, which leads to decreased survival.

Isolated Ruptured Paravisceral Penetrating Aortic Ulcers.

Background: The goal of this study is to investigate the clinical presentation, treatment options, and outcomes of the patients with isolated ruptured paravisceral penetrating aortic ulcers (PV-PAU).

Methods: All patients presenting with acute aortic syndrome from 2015 to 2020 were screened, of which patients with isolated ruptured PV-PAU were included in this retrospective study. Study endpoints were the assessment of treatment options, technical success, and clinical outcome.

Assessment of a Program for SARS-CoV-2 Screening and Environmental Monitoring in an Urban Public School District.

Importance: Scalable programs for school-based SARS-CoV-2 testing and surveillance are needed to guide in-person learning practices and inform risk assessments in kindergarten through 12th grade settings.

Objectives: To characterize SARS-CoV-2 infections in staff and students in an urban public school setting and evaluate test-based strategies to support ongoing risk assessment and mitigation for kindergarten through 12th grade in-person learning.

Design, Setting, And Participants: This pilot quality improvement program engaged 3 schools in Omaha, Nebraska, for weekly saliva polymerase chain reaction testing of staff and students participating in in-person learning over a 5-week period from November 9 to December 11, 2020.

[25-Gauge macular surgery: comparison with and without combined phacoemulsification and artificial lens implantation].

Background: With the surgical methods continuously developed in recent years, macular surgery has become an increasingly less traumatic procedure for the eye. For patients with additional lens opacification, a 1-stage procedure with combined cataract surgery is recommended.

Objective: The aim of this retrospective study was to record the functional results and complications after elective macular surgery with and without combined phacoemulsification and artificial lens implantation.

Stabilized epithelial phenotype of cancer cells in primary tumors leads to increased colonization of liver metastasis in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is therapeutically recalcitrant and metastatic. Partial epithelial to mesenchymal transition (EMT) is associated with metastasis; however, a causal connection needs further unraveling. Here, we use single-cell RNA sequencing and genetic mouse models to identify the functional roles of partial EMT and epithelial stabilization in PDAC growth and metastasis.

Aortoduodenal fistulas after endovascular abdominal aortic aneurysm repair and open aortic repair.

Objective: In the present study, we have reported and compared aortoduodenal fistulas (ADFs) after endovascular abdominal aortic aneurysm repair (EVAR) vs after open aortic repair (OAR).

Methods: We retrospectively analyzed the data from patients treated for ADFs from January 2015 to May 2020 in our hospital. The clinical data, diagnostic procedures, and surgical options were evaluated.

Incidence of Retinal Detachment after Macular Surgery.

Macular surgery has become an increasingly atraumatic procedure for the eye with the surgical methods that have been further developed in recent years. The most common complications include cystoid macular oedema and retinal detachment, more rarely endophthalmitis. The aim of this retrospective study is to record the number of retinal detachments following elective macular surgery.