Computational fluid particle dynamics modeling of tangential flow filtration in perfusion cell culture.

Membrane fouling is a common and complex challenge with cell culture perfusion process in biopharmaceutical manufacturing that can have detrimental effects on the process performance. In this study, we evaluated a method to calculate the hollow fiber membrane resistance at different time points for water and supernatant. In addition, the number of subvisible particles of < 200 nm.

Long-Term Cognitive Safety of Achieving Very Low LDL Cholesterol with Evolocumab.

Background: Concerns persist regarding the cognitive safety of achieving very low levels of low-density lipoprotein (LDL) cholesterol. Although short-term studies are reassuring, the long-term cognitive effects of sustained exposure to very low LDL cholesterol levels through combined proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibition and statin therapy remain unknown.

Methods: This prospective study enrolled a subset of adults with atherosclerotic cardiovascular disease who had completed a neurocognitive substudy (EBBINGHAUS) of a placebo-controlled randomized trial of evolocumab (FOURIER) and were eligible for a long-term open-label extension.

miR-29 is an important driver of aging-related phenotypes.

Aging is a consequence of complex molecular changes, but whether a single microRNA (miRNA) can drive aging remains unclear. A miRNA known to be upregulated during both normal and premature aging is miR-29. We find miR-29 to also be among the top miRNAs predicted to drive aging-related gene expression changes.

Feature-specific nutrient management of onion (Allium cepa) using machine learning and compositional methods.

While onion cultivars, irrigation and soil and crop management have been given much attention in Brazil to boost onion yields, nutrient management at field scale is still challenging due to large dosage uncertainty. Our objective was to develop an accurate feature-based fertilization model for onion crops. We assembled climatic, edaphic, and managerial features as well as tissue tests into a database of 1182 observations from multi-environment fertilizer trials conducted during 13 years in southern Brazil.

Artificial intelligence for oral squamous cell carcinoma detection based on oral photographs: A comprehensive literature review.

Introduction: Oral squamous cell carcinoma (OSCC) presents a significant global health challenge. The integration of artificial intelligence (AI) and computer vision holds promise for the early detection of OSCC through the analysis of digitized oral photographs. This literature review explores the landscape of AI-driven OSCC automatic detection, assessing both the performance and limitations of the current state of the art.

Twenty-four-hour urine oxalate and risk of chronic kidney disease.

Background: To assess whether 24-h urine oxalate (UOx) excretion is a risk factor for incident chronic kidney disease (CKD).

Methods: This longitudinal observational USA-based study included 426 896 individuals aged ≥18 years with no CKD at baseline and with at least one UOx, and at least 6 months of baseline and 6 months of follow-up data. Of these, 11 239 (2.

Efficacy and safety of a synthetic biotic for treatment of phenylketonuria: a phase 2 clinical trial.

Despite available treatment options, many patients with phenylketonuria (PKU) cannot achieve target plasma phenylalanine (Phe) levels. We previously modified Escherichia coli Nissle 1917 to metabolize Phe in the gut after oral administration (SYNB1618) and designed a second strain (SYNB1934) with enhanced activity of phenylalanine ammonia lyase. In a 14-day open-label dose-escalation study (Synpheny-1, NCT04534842 ), we test a primary endpoint of change from baseline in labeled Phe (D5-Phe AUC; D5-Phe area under the curve (AUC) over 24 hours after D5-Phe administration) in plasma after D5-Phe challenge in adult participants with screening Phe of greater than 600 µM.

Treatment with gut-specific nonsteroidal anti-inflammatory drug attenuates metabolic inflammation but not body mass in fattening ground squirrels.

The active season of hibernators corresponds to rapid adiposity in preparation for the next hibernation season. We have previously shown that this dramatic increase in adipose mass is associated with metabolic inflammation similar to what is seen in obesity and metabolic disease. We next sought to determine whether curbing this inflammation at its source (i.

What's gut got to do with it? The role of the microbiota and inflammation in the development of adiposity and obesity.

Obesity is a complex and heterogeneous disease characterized by increased adiposity, ie, the accumulation of lipids and the growth of adipose tissue. In this mini-review, we explore the important role of the gut microbiota and immune system in the development of adiposity. Dysbiosis of the microbiota leads to increased permeability of the gut barrier and bacterial products in the bloodstream, which triggers metabolic inflammation of adipose tissue, muscle, and liver.

Cyclic-AMP response element binding protein (CREB) and microRNA miR-29b regulate renalase gene expression under catecholamine excess conditions.

Aims: Renalase, a key mediator of cross-talk between kidneys and sympathetic nervous system, exerts protective roles in various cardiovascular/renal disease states. However, molecular mechanisms underpinning renalase gene expression remain incompletely understood. Here, we sought to identify the key molecular regulators of renalase under basal/catecholamine-excess conditions.

The Highly Reliable, Patient-Centered Sports Medicine Practice.

Patient-centered care is safe and eliminates preventable patient harm. Sports medicine teams that understand and apply the principles of high reliability, as demonstrated by high-performing communities in the US Navy, will provide safer, higher-quality care. Sustaining high-reliability performance is challenging.

Tumor Volume Predicts for Pathologic Complete Response in Rectal Cancer Patients Treated With Neoadjuvant Chemoradiation.

Objectives: Nonoperative management (NOM) of locally advanced rectal cancer is an emerging approach allowing patients to preserve their anal sphincter. Identifying clinical factors associated with pathologic complete response (pCR) is essential for physicians and patients considering NOM.

Materials And Methods: In total, 412 locally advanced rectal cancer patients were included in this retrospective analysis.

Factors Indicating Surgical Excision in Classical Type of Lobular Neoplasia of the Breast.

Purpose: Classical type of lobular neoplasia (LN) encompassing both atypical lobular hyperplasia and classical lobular carcinoma in situ of the breast is a lesion with uncertain malignant potential and has been the topic of several studies with conflicting outcome results. The aim of our study was to clarify outcome-relevant factors and treatment options of classical LN.

Methods: We performed a pathological re-evaluation of the preoperative biopsy specimens and a retrospective clinical and radiological data analysis of 160 patients with LN from the Breast Center Zurich.

No association between APOE genotype and lipid lowering with cognitive function in a randomized controlled trial of evolocumab.

APOE encodes a cholesterol transporter, and the ε4 allele is associated with higher circulating cholesterol levels, ß-amyloid burden, and risk of Alzheimer's disease. Prior studies demonstrated no significant differences in objective or subjective cognitive function for patients receiving the PCSK9 inhibitor evolocumab vs. placebo added to statin therapy.

An engineered bacterial therapeutic lowers urinary oxalate in preclinical models and in silico simulations of enteric hyperoxaluria.

Enteric hyperoxaluria (EH) is a metabolic disease caused by excessive absorption of dietary oxalate leading to the formation of chronic kidney stones and kidney failure. There are no approved pharmaceutical treatments for EH. SYNB8802 is an engineered bacterial therapeutic designed to consume oxalate in the gut and lower urinary oxalate as a potential treatment for EH.

The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Curation Expert Panel consensus guidelines for LDLR variant classification.

Purpose: In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published consensus standardized guidelines for sequence-level variant classification in Mendelian disorders. To increase accuracy and consistency, the Clinical Genome Resource Familial Hypercholesterolemia (FH) Variant Curation Expert Panel was tasked with optimizing the existing ACMG/AMP framework for disease-specific classification in FH. In this study, we provide consensus recommendations for the most common FH-associated gene, LDLR, where >2300 unique FH-associated variants have been identified.

Using a human factors-centric approach to development and testing of a face shield designed for health care workers: A COVID-19 case study for process and outcomes.

Background: Face shields are a critical piece of personal protective equipment and their comfort impacts compliant use and thus protectiveness. Optimal design criteria for face shield use in healthcare environments are limited. We attempt to identify factors affecting face shield usability and to test and optimize a face shield for comfort and function in health care settings.

X-ray multi-probe data acquisition: A novel technique for laser pump x-ray transient absorption spectroscopy.

We report the development and implementation of a novel data acquisition (DAQ) technique for synchrotron-based laser pump X-ray Transient Absorption (XTA) spectroscopy, called X-ray Multi-Probe DAQ (XMP DAQ). This technique utilizes high performance analog to digital converters and home-built software to efficiently measure and process the XTA signal from all x-ray pulses between laser excitations. XMP DAQ generates a set of time resolved x-ray absorption spectra at thousands of different pump-probe time delays simultaneously.

Gut microbiome is affected by gut region but robust to host physiological changes in captive active-season ground squirrels.

Background: Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) are obligate hibernators and are only active 4-5 months annually. During this period, squirrels rapidly acquire fat for use during hibernation. We investigated how the gut microbiome changed over the active season in the mucosa and lumen of two gut sections: the cecum and ileum.

Safety and pharmacodynamics of an engineered E. coli Nissle for the treatment of phenylketonuria: a first-in-human phase 1/2a study.

Phenylketonuria (PKU) is a rare disease caused by biallelic mutations in the PAH gene that result in an inability to convert phenylalanine (Phe) to tyrosine, elevated blood Phe levels and severe neurological complications if untreated. Most patients are unable to adhere to the protein-restricted diet, and thus do not achieve target blood Phe levels. We engineered a strain of E.

Pembrolizumab with Capox Bevacizumab in patients with microsatellite stable metastatic colorectal cancer and a high immune infiltrate: The FFCD 1703-POCHI trial.

Pembrolizumab, a PD1 immune checkpoint inhibitor (ICI), was recently reported to be very effective in patients with microsatellite instable/deficient mismatch repair metastatic colorectal cancer (MSI/dMMR mCRC), unlike patients with microsatellite stable/proficient MMR (MSS/pMMR) mCRC, in whom ICIs are generally ineffective. However, about 15% of MSS/pMMR CRCs are highly infiltrated by tumour infiltrating lymphocytes. In addition, both oxaliplatin and bevacizumab have been shown to have immunomodulatory properties that may increase the efficacy of an ICI.

Development of metabolic inflammation during pre-hibernation fattening in 13-lined ground squirrels (Ictidomys tridecemlineatus).

Obesity is a worldwide pandemic with significant comorbidities. It is often accompanied by mild inflammation of the intestine followed by inflammation of metabolic tissues such as liver, adipose tissue, and skeletal muscle. Several laboratory models of obesity exist, but seasonal models like hibernators may be valuable for understanding the pathogenesis of obesity independent of genetic or high-fat diet-induced changes.