Spatial transcriptomics analysis of neoadjuvant cabozantinib and nivolumab in advanced hepatocellular carcinoma identifies independent mechanisms of resistance and recurrence.

Background: Novel immunotherapy combination therapies have improved outcomes for patients with hepatocellular carcinoma (HCC), but responses are limited to a subset of patients. Little is known about the inter- and intra-tumor heterogeneity in cellular signaling networks within the HCC tumor microenvironment (TME) that underlie responses to modern systemic therapy.

Methods: We applied spatial transcriptomics (ST) profiling to characterize the tumor microenvironment in HCC resection specimens from a prospective clinical trial of neoadjuvant cabozantinib, a multi-tyrosine kinase inhibitor that primarily blocks VEGF, and nivolumab, a PD-1 inhibitor in which 5 out of 15 patients were found to have a pathologic response at the time of resection.

Sorption of As, Cd, and Pb by soil amendments: in situ immobilization mechanisms and implementation in contaminated agricultural soils.

The contamination of agricultural soils by toxic heavy metals, such as As, Cd, and Pb, is of great concern for crop safety as well as environmental and public health. Various adsorbents for the in situ immobilization of these metals have been widely studied, but researches on the potential and superiority of metal adsorption in agricultural soil amendments are still lacking. This study was conducted to investigate the nature of their sorption processes on soil amendments including slaked lime (SL), phosphogypsum (PG), bone meal (BM), and biochar (BC) using a series of laboratory batch tests.

Incorporation of Cell-Adhesive Proteins in 3D-Printed Lipoic Acid-Maleic Acid-Poly(Propylene Glycol)-Based Tough Gel Ink for Cell-Supportive Microenvironment.

In extrusion-based 3D printing, the use of synthetic polymeric hydrogels can facilitate fabrication of cellularized and implanted scaffolds with sufficient mechanical properties to maintain the structural integrity and physical stress within the in vivo conditions. However, synthetic hydrogels face challenges due to their poor properties of cellular adhesion, bioactivity, and biofunctionality. New compositions of hydrogel inks have been designed to address this limitation.

Informing virtual clinical trials of hepatocellular carcinoma with spatial multi-omics analysis of a human neoadjuvant immunotherapy clinical trial.

Human clinical trials are important tools to advance novel systemic therapies improve treatment outcomes for cancer patients. The few durable treatment options have led to a critical need to advance new therapeutics in hepatocellular carcinoma (HCC). Recent human clinical trials have shown that new combination immunotherapeutic regimens provide unprecedented clinical response in a subset of patients.

Ridge mini-implants, a versatile biomechanical anchorage device whose success is significantly enhanced by splinting: a clinical report.

Objectives: This clinical report aims to highlight the factors affecting the clinical success of alveolar ridge mini-implants used for orthodontic anchorage and provide an overview of the biomechanical versatility of this miniscrew and steps involving the proper technique of its placement.

Methods: For this clinical report, charts for 295 patients who had temporary anchorage devices (TADs) were screened. Twenty patients [15 females and 5 males: mean age = 38.

Clinicopathologic Significance of Heat Shock Protein 60 as a Survival Predictor in Colorectal Cancer.

The role of heat shock protein 60 (HSP60), a mitochondrial chaperone, in tumor progression or its anti-tumor effects remains controversial. This study aimed to confirm the possibility of using HSP60 as a prognostic marker in patients with colorectal cancer (CRC), considering TNM classification for precise prediction. HSP60 expression increased with differentiation and p53 mutations in patients.

Study on Bioresponsive Gelatin-Hyaluronic Acid-Genipin Hydrogel for High Cell-Density 3D Bioprinting.

The Development of bioresponsive extrudable hydrogels for 3D bioprinting is imperative to address the growing demand for scaffold design as well as efficient and reliable methods of tissue engineering and regenerative medicine. This study proposed genipin (5 mg) cross-linked gelatin (1 to 1.5 g)-hyaluronic acid (0.

Transcriptomic forecasting with neural ordinary differential equations.

Single-cell transcriptomics technologies can uncover changes in the molecular states that underlie cellular phenotypes. However, understanding the dynamic cellular processes requires extending from inferring trajectories from snapshots of cellular states to estimating temporal changes in cellular gene expression. To address this challenge, we have developed a neural ordinary differential-equation-based method, RNAForecaster, for predicting gene expression states in single cells for multiple future time steps in an embedding-independent manner.

Exploring the Relationships Among (COVID)-19 Stress, Leisure Constraints, and Happiness for Adults During the (COVID)-19 Pandemic in Korea.

The emergence of COVID-19 and its consequences has led to fears, worries, discomfort, depression, and anxiety for human beings worldwide. In this study, we examined the relationships among COVID-19 stress, leisure constraints, and happiness of Korean adults. We employed on-line convenience sampling to recruit participants.

The miR-17∼92 miRNAs promote plasma cell differentiation by suppressing SOCS3-mediated NIK degradation.

The miR-17∼92 family microRNAs (miRNAs) play a key role in germinal center (GC) reaction through promoting T follicular helper (T) cell differentiation. It remains unclear whether they also have intrinsic functions in B cell differentiation and function. Here we show that mice with B cell-specific deletion of the miR-17∼92 family exhibit impaired GC reaction, plasma cell differentiation, and antibody production in response to protein antigen immunization and chronic viral infection.

Analysis of Under-Diagnosed Malignancy during Fine Needle Aspiration Cytology of Lymphadenopathies.

Fine needle aspiration cytology (FNAC) is a useful tool in the evaluation of lymphadenopathy. It is a safe and minimally invasive procedure that provides preoperative details for subsequent treatment. It can also diagnose the majority of malignant tumors.

Comparing the Effectiveness of Physical Rehabilitation Interventions for Post-Stroke Function and Mobility Recovery: A Meta-Analysis.

Various interventions to physical rehabilitation have been used after stroke, including musculoskeletal, neurophysiological, and motor learning interventions, with ongoing debates and controversies about their relative effectiveness. In this systematic review, we searched 3 international electronic databases (MEDLINE, Embase, and Cochrane Library) to identify relevant studies. We included only randomized controlled trials (RCTs) that directly compared motor relearning, neurophysiological, and musculoskeletal interventions for improving motor function in adult stroke patients.

Does physical activity moderate the association between shorter leukocyte telomere length and incident coronary heart disease? Data from 54,180 UK Biobank participants.

Telomere shortening is a biological aging hallmark. The effect of short telomere length may be targeted by increased physical activity to reduce the risk of multiple aging-related diseases, including coronary heart disease (CHD). The objective was to assess the moderation effect of accelerometer-based physical activity (aPA) on the association between shorter leukocyte telomere length (LTL) relatively in the population sample and incident CHD.

Fast-Embeddable Grooved Microneedles by Shear Actuation for Accurate Transdermal Drug Delivery.

Percutaneous drug delivery using microneedles (MNs) has been extensively exploited to increase the transdermal permeability of therapeutic drugs. However, it is difficult to control the precise dosage with existing MNs and they need to be attached for a long time, so a more simple and scalable method is required for accurate transdermal drug delivery. In this study, we developed grooved MNs that can be embedded into the skin by mechanical fracture following simple shear actuation.

Evaluation of the Chemosensoric Properties of Commercially Available Dog Foods Using Electronic Sensors and GC-MS/O Analysis.

Pet owners think of their animals as part of their family, which further promotes the growth of the pet food market, encouraging pet owners to select nutritious, palatable, and high-quality foods for pets. Therefore, the evaluation of taste and volatile compounds in pet foods is essential to improve palatability. In this study, the sensory characteristics of taste and odor compounds in 10 commercially available dry dog foods were investigated using electronic tongue (E-tongue), electronic nose (E-nose), gas chromatography-mass spectrometry (GC-MS), and gas chromatography-olfactometry (GC-O).

Characterization of Growth-Promoting Activities of Consortia of Chlorpyrifos Mineralizing Endophytic Bacteria Naturally Harboring in Rice Plants-A Potential Bio-Stimulant to Develop a Safe and Sustainable Agriculture.

Eighteen pesticide-degrading endophytic bacteria were isolated from the roots, stems, and leaves of healthy rice plants and identified through 16S rRNA gene sequencing. Furthermore, biochemical properties, including enzyme production, dye degradation, anti-bacterial activities, plant-growth-promoting traits, including N-fixation, P-solubilization, auxin production, and ACC-deaminase activities of these naturally occurring endophytic bacteria along with their four consortia, were characterized. HSTU-ABk39 and sp.

Assessment of clear aligner accuracy of 2 clear aligners systems.

Introduction: This study compared treatment efficacy for specific tooth movements between 2 clear aligner systems (Clarity [3M Oral Care Solutions, St Paul, Minn] and Invisalign [Align Technology, San Jose, Calif]).

Methods: The study sample included 47 patients (7 males, 40 females; mean age, 36.57 ± 15.

Receptor-specific contributions of caveolae, PKC, and Src tyrosine kinase to serotonergic and adrenergic regulation of Kv channels and vasoconstriction.

Aims: Caveolae are invaginated, Ω-shaped membrane structures. They are now recognized as portals for signal transduction of multiple chemical and mechanical stimuli. Notably, the contribution of caveolae has been reported to be receptor-specific.

Complete Genome Analysis of sp. PAMC28395: Genomic Insights into Its Potential Role for Cold Adaptation and Biotechnological Applications.

This study reports the complete genome sequence of sp. PAMC28395, a strain isolated from cryoconite in Uganda. This strain possesses several active carbohydrate-active enzyme (CAZyme) genes involved in glycogen and trehalose metabolism.

3D bioprinting of complex tissue scaffolds with in situ homogeneously mixed alginate-chitosan-kaolin bioink using advanced portable biopen.

Control of in situ 3D bioprinting of hydrogel without toxic crosslinker is ideal for tissue regeneration by reinforcing and homogeneously distributing biocompatible reinforcing agent during fabrication of large area and complex tissue engineering scaffolds. In this study, homogeneous mixing, and simultaneous 3D bioprinting of a multicomponent bioink based on alginate (AL)-chitosan (CH), and kaolin was obtained by an advanced pen-type extruder to ensure structural and biological homogeneity during the large area tissue reconstruction. The static, dynamic and cyclic mechanical properties as well as in situ self-standing printability significantly improved with the kaolin concentration for AL-CH bioink-printed samples due to polymer-kaolin nanoclay hydrogen bonding and cross-linking with less amount of calcium ions.

Colorectal cancer in patients of advanced age is associated with increased incidence of p.V600E mutation and mismatch repair deficiency.

Introduction: The highest incidence of colorectal cancer (CRC) is in patients diagnosed at 80 years or older highlighting a need for understanding the clinical and molecular features of these tumors. Methods. In this retrospective cohort study, 544 CRCs underwent next generation sequencing and mismatch repair (MMR) evaluation.

A platform trial of neoadjuvant and adjuvant antitumor vaccination alone or in combination with PD-1 antagonist and CD137 agonist antibodies in patients with resectable pancreatic adenocarcinoma.

A neoadjuvant immunotherapy platform clinical trial allows for rapid evaluation of treatment-related changes in tumors and identifying targets to optimize treatment responses. We enrolled patients with resectable pancreatic adenocarcinoma into such a platform trial (NCT02451982) to receive pancreatic cancer GVAX vaccine with low-dose cyclophosphamide alone (Arm A; n = 16), with anti-PD-1 antibody nivolumab (Arm B; n = 14), and with both nivolumab and anti-CD137 agonist antibody urelumab (Arm C; n = 10), respectively. The primary endpoint for Arms A/B - treatment-related change in IL17A expression in vaccine-induced lymphoid aggregates - was previously published.