Sialic acids on T cells are crucial for their maintenance and survival.

Sialic acids are found as terminal sugars on glycan structures on cellular surfaces. T cells carry these sialoglycans abundantly, and they are thought to serve multiple functions in cell adhesion, cell migration, and protection from complement attack. We studied the role of sialoglycans on T cells in a mouse model with a T cell-specific deletion of cytidine monophosphate-sialic acid synthase (CMAS), the enzyme that is crucial for the synthesis of sialoglycans.

Treatment of critical bone defects using calcium phosphate cement and mesoporous bioactive glass providing spatiotemporal drug delivery.

Calcium phosphate cements (CPC) are currently widely used bone replacement materials with excellent bioactivity, but have considerable disadvantages like slow degradation. For critical-sized defects, however, an improved degradation is essential to match the tissue regeneration, especially in younger patients who are still growing. We demonstrate that a combination of CPC with mesoporous bioactive glass (MBG) particles led to an enhanced degradation and in a critical alveolar cleft defect in rats.

Navigating large chemical spaces in early-phase drug discovery.

The size of actionable chemical spaces is surging, owing to a variety of novel techniques, both computational and experimental. As a consequence, novel molecular matter is now at our fingertips that cannot and should not be neglected in early-phase drug discovery. Huge, combinatorial, make-on-demand chemical spaces with high probability of synthetic success rise exponentially in content, generative machine learning models go hand in hand with synthesis prediction, and DNA-encoded libraries offer new ways of hit structure discovery.

Entrapment of the index finger radial collateral ligament in the metacarpophalangeal joint: A case report.

Introduction: Digital collateral ligament injuries are common hand injuries that can cause significant pain and functional impairment. Ultrasonography can be useful in the evaluation of these ligamentous injuries, as it is both cost-effective and allows for easy, dynamic evaluation during imaging.

Case Report: We report a rare sonographic finding of an index finger radial collateral ligament injury that was found to have a flap of the ligament entrapped within the metacarpophalangeal joint, which to our knowledge has not been described previously.

Epistatic effects of Siglec-G and DNase1 or DNase1l3 deficiencies in the development of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a severe autoimmune disease that displays considerable heterogeneity not only in its symptoms, but also in its environmental and genetic causes. Studies in SLE patients have revealed that many genetic variants contribute to disease development. However, often its etiology remains unknown.

Mineral and Trace Elements in Nutritious Flours: Total Contents, In Vitro Bioaccessibility and Contribution to Dietary Intake.

The consumption of fruits, vegetables, and cereals in the form of flour has been an alternative for the intake of nutrients, currently seen in a society that seeks a healthier diet. Thus, the assessment of total contents and bioaccessibility is important to better understand the actual intake of nutrients or contaminants present in foods. The objective of this study was to determine the total content and estimate the bioaccessible fraction of Cu, Fe, and Zn in nutritious flours by inductively coupled plasma optical emission spectrometry (ICP OES) after microwave acid digestion.

What are the Minimum Clinically Important Difference Values for the PROMIS and QuickDASH After Carpal Tunnel Release? A Prospective Cohort Study.

Background: To better define the clinical significance of patient-reported outcomes, the concept of a minimum clinically important difference (MCID) exists. The MCID is the minimum change that a patient will perceive as meaningful. Prior attempts to determine the MCID after carpal tunnel release are limited by methodologic concerns, including the lack of a true anchor-based MCID calculation.

SARS-CoV-2 triggered seizure complicated by fatal subdural hematoma under edoxaban and clopidogrel.

SARS-CoV-2 associated coagulopathy may manifest as hypocoagulability with a propensity for bleeding. Here we report a COVID-19 patient with fatal subdural hematoma (SDH) shortly after thrombendarteriectomy (TEA), and anticoagulation together with anti-thrombotic treatment. A 83-year-old male developed sudden-onset fever triggering a first ever tonic-clonic seizure.

Preclinical pharmacology of RA15127343: In vitro and in vivo activity of a novel ultralong-acting basal insulin.

Aim: To report the in vitro and in vivo preclinical pharmacokinetic (PK) and pharmacodynamic (PD) properties of RA15127343, a novel ultralong-acting insulin analogue targeting once-weekly administration, in female Göttingen minipigs.

Methods: In vitro binding and activation of human insulin receptor isoforms (IR-A/IR-B), glucose uptake in rat myocytes, as well as mitogenic activity of RA15127343 were evaluated. In vivo, the PK and PD activities of RA15127343 were assessed in female, normoglycaemic Göttingen minipigs.

Effect of losartan potassium, metformin hydrochloride, and simvastatin on in vitro bioaccessibility of Cu, Fe, Mn, and Zn in oat flour from Brazil.

Background: The simultaneous administration of drugs with food can compromise the bioaccessibility and absorption of nutrients. The objective of this study was to evaluate the influence of the use of losartan potassium (LP), metformin hydrochloride (MH), and simvastatin (S) on the in vitro bioaccessibility of micronutrients (Cu, Fe, Mn, and Zn) in oat flour from Bahia, Brazil.

Methods: The experimental procedure consisted of the in vitro extraction of the bioaccessible fraction of Cu, Fe, Mn, and Zn in oat flour-with and without LP (50 mg), MH (500 mg), and S (20 mg)-using the unified bioaccessibility method (UBM), simulating the conditions of the gastrointestinal tract.

Benefit from upfront FOLFOXIRI and bevacizumab in BRAFV600E-mutated metastatic colorectal cancer patients: does primary tumour location matter?

Background: Recent data suggest that BRAFV600E-mutated metastatic colorectal cancer (mCRC) patients with right-sided tumours and ECOG-PS = 0 may achieve benefit from the triplet regimen differently than those with left-sided tumours and ECOG-PS > 0.

Methods: The predictive impact of primary sidedness and ECOG-PS was evaluated in a large real-life dataset of 296 BRAFV600E-mutated mCRC patients treated with upfront triplet or doublet ± bevacizumab. Biological differences between right- and left-sided BRAFV600E-mutated CRCs were further investigated in an independent cohort of 1162 samples.

Pomegranate juice alters the microbiota in breast milk and infant stool: a pilot study.

Pomegranate juice (PomJ) contains ellagitannins (ETs) that are metabolized to ellagic acid (EA). Intestinal bacteria convert EA further to urolithins that are absorbed into the circulation and may provide health benefits. PomJ consumption by pregnant women was reported to be neuroprotective for their infants.

FOLFOXIRI and bevacizumab in patients with early-onset metastatic colorectal cancer. A pooled analysis of TRIBE and TRIBE2 studies.

Background: We performed a pooled analysis of TRIBE and TRIBE2 studies to assess the efficacy and safety of the intensification of upfront chemotherapy backbone - from doublets to the triplet FOLFOXIRI - in combination with bevacizumab (bev) in patients with early-onset metastatic colorectal cancer (EO-mCRC; aged <50 years) and to explore whether EO-mCRCs have a peculiar tumour genomic profiling.

Materials And Methods: Subgroup analyses according to age (<50 versus ≥50 years) and treatment (FOLFOXIRI/bev versus doublets/bev) were carried out for rates of any grade and grade ≥3 (≥G3) overall and singular adverse events, progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). Tumour genomic profiling was obtained using a DNA-based next-generation sequencing platform.

Survival and Detection of Bivalve Transmissible Neoplasia from the Soft-Shell Clam (MarBTN) in Seawater.

Many pathogens can cause cancer, but cancer itself does not normally act as an infectious agent. However, transmissible cancers have been found in a few cases in nature: in Tasmanian devils, dogs, and several bivalve species. The transmissible cancers in dogs and devils are known to spread through direct physical contact, but the exact route of transmission of bivalve transmissible neoplasia (BTN) has not yet been confirmed.

Pseudouridine synthase 7 is an opportunistic enzyme that binds and modifies substrates with diverse sequences and structures.

Pseudouridine (Ψ) is a ubiquitous RNA modification incorporated by pseudouridine synthase (Pus) enzymes into hundreds of noncoding and protein-coding RNA substrates. Here, we determined the contributions of substrate structure and protein sequence to binding and catalysis by pseudouridine synthase 7 (Pus7), one of the principal messenger RNA (mRNA) modifying enzymes. Pus7 is distinct among the eukaryotic Pus proteins because it modifies a wider variety of substrates and shares limited homology with other Pus family members.

Characterization and manipulation of Corticothalamic neurons in associative cortices using Syt6-Cre transgenic mice.

Corticothalamic interactions between associative cortices and higher order thalamic nuclei are involved in high-cognitive functions such as decision-making and working memory. Corticothalamic neurons (CTn) in the prefrontal cortex and other associative areas have been much less studied than their counterparts in the primary sensory areas. The availability of characterized transgenic tools to study CTn in associative areas will facilitate their study and contribute to overcome the scarcity of data about their properties, network dynamics, and contribution to cognitive functions.

Renal hemodynamic effects differ between antidiabetic combination strategies: randomized controlled clinical trial comparing empagliflozin/linagliptin with metformin/insulin glargine.

Background: Type 2 diabetes causes cardio-renal complications and is treated with different combination therapies. The renal hemodynamics profile of such combination therapies has not been evaluated in detail.

Methods: Patients (N = 97) with type 2 diabetes were randomized to receive either empagliflozin and linagliptin (E+L group) or metformin and insulin glargine (M+I group) for 3 months.

Homologous Recombination Deficiency Alterations in Colorectal Cancer: Clinical, Molecular, and Prognostic Implications.

Background: Tumors with homologous recombination deficiency (HRD) show high sensitivity to platinum salts and poly(ADP-ribose) polymerase-inhibitors in several malignancies. In colorectal cancer (CRC), the role of HRD alterations is mostly unknown.

Methods: Next-generation sequencing, whole transcriptome sequencing, and whole exome sequencing were conducted using CRC samples submitted to a commercial Clinical Laboratory Improvement Amendments certified laboratory.

Evaluation of slurry sampling preparation of enteral nutrition formulations for multielement determination using inductively coupled plasma optical emission spectrometry.

An analytical procedure for the multielement determination in enteral nutrition formulations employing slurry sampling and inductively coupled plasma optical emission spectrometry (ICP OES) is proposed. A two-level full-factorial design was applied to assess the influence of the presence of stabilizing agents (HNO, Triton X-100 and ethanol) on the composition of the slurry. Multiple response was established as a dependent variable.

Aphasia seven days after second dose of an mRNA-based SARS-CoV-2 vaccine.

Objectives: Though rare, neurological side effects of SARS-CoV-2 vaccinations are increasingly reported. Even if the first dosage goes uncomplicated, the second dose may be complicated by severe adverse reactions as in the following case.

Case Report: A 52yo male developed sudden-onset reading difficulty and aphasia 7d after the second dose of an mRNA-based SARS-CoV-2 vaccine.

Gliosarcoma vs. glioblastoma: a retrospective case series using molecular profiling.

Background: Gliosarcoma (GS) refers to the presence of mesenchymal differentiation (as seen using light microscopy) in the setting of glioblastoma (GB, an astrocytoma, WHO Grade 4). Although the same approach to treatment is typically adopted for GS and GB, there remains some debate as to whether GS should be considered a discrete pathological entity. Differences between these tumors have not been clearly established at the molecular level.

Expression patterns of the immune checkpoint ligand CD276 in urothelial carcinoma.

Background: CD276 is an immune checkpoint molecule. Elevated CD276 expression by urothelial carcinoma is associated with poor prognosis, but little is known about its expression across different tumor stages. We therefore investigated CD276 expression in bladder cancer (BC) cells and in tissue samples of BC stages from pT2 to pT4.