Microfluidic chip systems for characterizing glucose-responsive insulin-secreting cells equipped with FailSafe kill-switch.

Background: Pluripotent cell-derived islet replacement therapy offers promise for treating Type 1 diabetes (T1D), but concerns about uncontrolled cell proliferation and tumorigenicity present significant safety challenges. To address the safety concern, this study aims to establish a proof-of-concept for a glucose-responsive, insulin-secreting cell line integrated with a built-in FailSafe kill-switch.

Method: We generated β cell-induced progenitor-like cells (βiPLCs) from primary mouse pancreatic β cells through interrupted reprogramming.

Dynamic [Tc]Tc-mebrofenin SPECT/CT in preoperative planning of liver resection: a prospective study.

Background: At least 20% of the future liver remnant must function properly after liver tumor resection to avoid post-hepatectomy liver failure (PHLF). [Tc]Tc-mebrofenin scintigraphy and SPECT are unique noninvasive, quantitative methods for evaluating liver function via hepatocellular bilirubin clearance.

Aim: To evaluate the value of dynamic [Tc]Tc-mebrofenin SPECT/CT parameters for predicting clinically relevant PHLF according to the ISGLS criteria.

Substrate Stiffness Dictates Unique Doxorubicin-induced Senescence-associated Secretory Phenotypes and Transcriptomic Signatures in Human Pulmonary Fibroblasts.

Cells are subjected to dynamic mechanical environments which impart forces and induce cellular responses. In age-related conditions like pulmonary fibrosis, there is both an increase in tissue stiffness and an accumulation of senescent cells. While senescent cells produce a senescence-associated secretory phenotype (SASP), the impact of physical stimuli on both cellular senescence and the SASP is not well understood.

Trophic evolution in ornithopod dinosaurs revealed by dental wear.

Ornithopod dinosaurs evolved numerous craniodental innovations related to herbivory. Nonetheless, the relationship between occlusion, tooth wear rate, and tooth replacement rate has been neglected. Here, we reconstruct tooth wear rates by measuring tooth replacement rates and tooth wear volumes, and document their dental microwear.

Long-Term Safety of Facilitated Subcutaneous Immunoglobulin 10% Treatment in US Clinical Practice in Patients with Primary Immunodeficiency Diseases: Results from a Post-Authorization Safety Study.

Facilitated subcutaneous immunoglobulin (fSCIG) 10% is an immunoglobulin replacement therapy that utilizes recombinant human hyaluronidase (rHuPH20) to enhance immunoglobulin dispersion and absorption, allowing for longer treatment intervals similar to intravenous immunoglobulin (up to once monthly). fSCIG 10% is indicated in the USA for treating adults and children aged ≥ 2 years with primary immunodeficiency diseases (PIDs). This prospective, non-interventional, open-label, multicenter, post-authorization safety study (NCT02593188) was conducted in the USA from November 2015 to October 2021 to assess the long-term safety of fSCIG 10% in routine clinical practice.

In vitro digestion and fermentation characteristics of soluble dietary fiber from adlay (Coix lacryma-jobi L. var. ma-yuen Staft) bran modified by steam explosion.

Adlay bran is known for its nutrient-rich profile and multifunctional properties, and steam explosion (SE) is an emerging physical modification technique. However, the specific effects of SE on the activity composition and antioxidant capacity of adlay bran soluble dietary fiber (SDF) during in vitro digestion, as well as its influence on gut microbiota during in vitro fermentation, remain inadequately understood. This paper reports the in vitro digestion and fermentation characteristics of soluble dietary fiber from adlay bran modified by SE (SE-SDF).

The Circadian Clock of Müller Glia Is Necessary for Retinal Homeostasis and Neuronal Survival.

Biological processes throughout the body are orchestrated in time through the regulation of local circadian clocks. The retina is among the most metabolically active tissues, with demands depending greatly on the light/dark cycle. Most cell types within the rodent retina are known to express the circadian clock; however, retinal clock expression in humans has not previously been localized.

Impact of Selected Glucagon-like Peptide-1 Receptor Agonists on Serum Lipids, Adipose Tissue, and Muscle Metabolism-A Narrative Review.

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are novel antihyperglycemic agents. By acting through the central nervous system, they increase satiety and reduce food intake, thus lowering body weight. Furthermore, they increase the secretion of insulin while decreasing the production of glucagon.

Tolerability and Safety of Large-Volume Hyaluronidase-Facilitated Subcutaneous Immunoglobulin 10% Administered with or without Dose Ramp-Up: A Phase 1 Study in Healthy Participants.

Purpose: Facilitated subcutaneous immunoglobulin (fSCIG; immune globulin infusion 10% [human] with recombinant human hyaluronidase [rHuPH20]) permits high-volume subcutaneous immunoglobulin (SCIG) infusion, shorter infusion times and reduced dosing frequency relative to conventional SCIG. It is initiated by gradually increasing infusion volumes over time (dose ramp-up) to achieve target dose level (TDL). Whether ramp-up strategies have tolerability or safety advantages over direct initiation at full TDL has not been evaluated clinically.

Long-term safety of hyaluronidase-facilitated subcutaneous immunoglobulin 10%: a European post-authorization study.

To assess the long-term safety of hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% in European routine clinical practice. This prospective, noninterventional, open-label, post-authorization safety study (EUPAS5812) sourced data on adverse events, immunogenicity, treatment regimens and product administration for 106 adult patients prescribed fSCIG 10% across 17 sites in six European countries from July 2014 to February 2020. In total, 1171 treatment-emergent adverse events were reported in 94 patients (88.

A Comprehensive Overview on Chemotherapy-Induced Cardiotoxicity: Insights into the Underlying Inflammatory and Oxidative Mechanisms.

While oncotherapy has made rapid progress in recent years, side effects of anti-cancer drugs and treatments have also come to the fore. These side effects include cardiotoxicity, which can cause irreversible cardiac damages with long-term morbidity and mortality. Despite the continuous in-depth research on anti-cancer drugs, an improved knowledge of the underlying mechanisms of cardiotoxicity are necessary for early detection and management of cardiac risk.

Distribution and diversity of fishes and lampreys in Transylvania (Romania): a complete survey and suggestions for new protected areas.

Freshwater fishes are in a serious state of decline across the world, making them one of the most threatened groups of vertebrates. The Danube River catchment area in Europe holds the richest freshwater fish community, but our knowledge of the current distribution of these species is limited. Transylvania, the largest region of Romania, is one of the important tributaries of the Danube, from where 77 fish and two lamprey species were recorded until now.

Complex dental wear analysis reveals dietary shift in Triassic placodonts (Sauropsida, Sauropterygia).

Unlabelled: Placodonts were durophagous reptiles of the Triassic seas with robust skulls, jaws, and enlarged, flat, pebble-like teeth. During their evolution, they underwent gradual craniodental changes from the Early Anisian to the Rhaetian, such as a reduction in the number of teeth, an increase in the size of the posterior palatal teeth, an elongation of the premaxilla/rostrum, and a widening of the temporal region. These changes are presumably related to changes in dietary habits, which, we hypothesise, are due to changes in the type and quality of food they consumed.

A Phase 1 Open-Label Study to Assess the Tolerability, Safety, and Immunogenicity of Hyaluronidase-Facilitated Subcutaneous Immunoglobulin 20% in Healthy Adults.

Purpose: Hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 20% will allow reduced infusion volumes and frequency versus existing subcutaneous therapies such as fSCIG 10% and conventional subcutaneous immunoglobulin 20%, respectively. We assessed the tolerability, safety, and immunogenicity of warmed and unwarmed fSCIG 20%.

Methods: This phase 1, single-dose, open-label, three-arm study enrolled healthy adults aged 19-50 years (inclusive) at a single US center (NCT05059977).

White blood cell subtypes and neutrophil extracellular traps content as biomarkers for stroke etiology in acute ischemic stroke clots retrieved by mechanical thrombectomy.

Background: Lymphocytes, macrophages, neutrophils, and neutrophil extracellular traps (NETs) associate with stroke risk factors and form a thrombus through different mechanisms. We investigated the total WBCs, WBC subtypes and NETs composition in acute ischemic stroke (AIS) clots to identify possible etiological differences that could help us further understand the process of thrombosis that leads to AIS.

Methods: AIS clots from 100 cases each of atherothrombotic (AT), cardioembolic (CE) and cryptogenic stroke etiology were collected per-pass as part of the CÚRAM RESTORE registry of AIS clots.

Immune-privileged tissues formed from immunologically cloaked mouse embryonic stem cells survive long term in allogeneic hosts.

The immunogenicity of transplanted allogeneic cells and tissues is a major hurdle to the advancement of cell therapies. Here we show that the overexpression of eight immunomodulatory transgenes (Pdl1, Cd200, Cd47, H2-M3, Fasl, Serpinb9, Ccl21 and Mfge8) in mouse embryonic stem cells (mESCs) is sufficient to immunologically 'cloak' the cells as well as tissues derived from them, allowing their survival for months in outbred and allogeneic inbred recipients. Overexpression of the human orthologues of these genes in human ESCs abolished the activation of allogeneic human peripheral blood mononuclear cells and their inflammatory responses.

Speckle-Tracking Strain Analysis for Mapping Spatiotemporal Contractility of Induced Pluripotent Stem Cell (iPSC)-Derived Cardiomyocytes.

Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) hold tremendous potential for cardiovascular disease modeling, drug screening, personalized medicine, and pathophysiology studies. The availability of a robust protocol and functional assay for studying phenotypic behavior of hiPSC-CMs is essential for establishing an in vitro disease model. Many heart diseases manifest due to changes in the mechanical strain of cardiac tissue.

Soluble CX3CL1-expressing retinal pigment epithelium cells protect rod photoreceptors in a mouse model of retinitis pigmentosa.

Background: Retinitis pigmentosa (RP) is an inherited retinal disease that results in photoreceptor degeneration, leading to severe vision loss or blindness. Due to its genetic heterogeneity, developing a new gene therapy to correct every genetic mutation contributing to its progression is infeasible. Photoreceptor transplantation can be harnessed to restore vision; however, this approach is limited by poor cell survival and synaptic integration into the neural retina.

The Interplay of Lifestyle and Adipokines in the Non-Obese Stroke-Prone Spontaneously Hypertensive Rats.

Although the morphological features and functions of adipose tissue are well-described in obesity-prone animal models, less information is available on animals such as the () strain with cardiovascular abnormalities, which is not characterized by excessive adiposity. Our aim was to focus on lifestyle-induced (type of diet and physical exercise) effects on adipokine profile and lipid peroxidation in rats. In our study, male (control) and rats were used.

[Cholangitis and cholecystitis: diagnostic criteria and management].

In developed countries, diseases of the gallbladder and the biliary tract count as some of the most frequent gastrointestinal disorders. The inflammation of the gallbladder/biliary tree is a potentially severe, even lethal condition that requires rapid diagnosis and early multidisciplinary approach to be treated. Although the frequency of these diseases is high, the treatment is not unified in Hungary yet.

[Role of interventional radiology in the treatment of primary and metastatic renal cancer].

More and more asymptomatic renal lesions are diagnosed as a result of the growing number of routine imaging examinations. Lesion characterization is often only possible with percutaneous biopsy. Stage T1 renal cell carcinoma is potentially curable not only by partial nephrectomy, but also with thermoablations.

Multi-proxy dentition analyses reveal niche partitioning between sympatric herbivorous dinosaurs.

Dentitions of the sympatric herbivorous dinosaurs Hungarosaurus (Ankylosauria, Nodosauridae) and Mochlodon (Ornithopoda, Rhabdodontidae) (Santonian, Hungary) were analysed to investigate their dietary ecology, using several complementary methods-orientation patch count, tooth replacement rate, macrowear, tooth wear rate, traditional microwear, and dental microwear texture analysis (DMTA). Tooth formation time is similar in Hungarosaurus and Mochlodon, and traditional and DMTA microwear features suggest low-browsing habits for both taxa, consistent with their inferred stances and body sizes. However, Mochlodon possesses a novel adaptation for increasing dental durability: the dentine on the working side of the crown is double the thickness of that on the balancing side.

Highly efficient reprogrammable mouse lines with integrated reporters to track the route to pluripotency.

Revealing the molecular events associated with reprogramming different somatic cell types to pluripotency is critical for understanding the characteristics of induced pluripotent stem cell (iPSC) therapeutic derivatives. Inducible reprogramming factor transgenic cells or animals-designated as secondary (2°) reprogramming systems-not only provide excellent experimental tools for such studies but also offer a strategy to study the variances in cellular reprogramming outcomes due to different in vitro and in vivo environments. To make such studies less cumbersome, it is desirable to have a variety of efficient reprogrammable mouse systems to induce successful mass reprogramming in somatic cell types.