Regorafenib monotherapy as the later-line treatment for elderly patients with metastatic colorectal cancer: a multicenter real-world study.

Background: Colorectal cancer is one of the tumors with the highest morbidity and mortality rates in China and the world. Regorafenib is a targeted drug for standard third-line treatment of metastatic colorectal cancer (mCRC). Regorafenib monotherapy has shown certain efficacy in the elderly population, but more robust evidence is needed.

De novo generation of SARS-CoV-2 antibody CDRH3 with a pre-trained generative large language model.

Artificial Intelligence (AI) techniques have made great advances in assisting antibody design. However, antibody design still heavily relies on isolating antigen-specific antibodies from serum, which is a resource-intensive and time-consuming process. To address this issue, we propose a Pre-trained Antibody generative large Language Model (PALM-H3) for the de novo generation of artificial antibodies heavy chain complementarity-determining region 3 (CDRH3) with desired antigen-binding specificity, reducing the reliance on natural antibodies.

Asparagine Synthetase Marks a Distinct Dependency Threshold for Cardiomyocyte Dedifferentiation.

Background: Adult mammalian cardiomyocytes have limited proliferative capacity, but in specifically induced contexts they traverse through cell-cycle reentry, offering the potential for heart regeneration. Endogenous cardiomyocyte proliferation is preceded by cardiomyocyte dedifferentiation (CMDD), wherein adult cardiomyocytes revert to a less matured state that is distinct from the classical myocardial fetal stress gene response associated with heart failure. However, very little is known about CMDD as a defined cardiomyocyte cell state in transition.

Co-expression of a PD-L1-specific chimeric switch receptor augments the efficacy and persistence of CAR T cells via the CD70-CD27 axis.

Co-expression of chimeric switch receptors (CSRs) specific for PD-L1 improves the antitumor effects of chimeric antigen receptor (CAR) T cells. However, the effects of trans-recognition between CSRs and PD-L1 expressed by activated CAR T cells remain unclear. Here, we design a CSR specific for PD-L1 (CARP), containing the transmembrane and cytoplasmic signaling domains of CD28 but not the CD3 ζ chain.

A Review on Manufacturing and Post-Processing Technology of Vascular Stents.

Percutaneous coronary intervention (PCI) with stent implantation is one of the most effective treatments for cardiovascular diseases (CVDs). However, there are still many complications after stent implantation. As a medical device with a complex structure and small size, the manufacture and post-processing technology greatly impact the mechanical and medical performances of stents.

Trajectories of Lymphocyte Counts in the Early Phase of Acute Pancreatitis Are Associated With Infected Pancreatic Necrosis.

Introduction: Infected pancreatic necrosis (IPN) is an important complication of acute pancreatitis (AP). Absolute lymphocyte count (ALC) was reported to be associated with immunosuppression and the development of IPN. The aim of this study was to describe the trajectory of ALC during the early phase of AP and assess its association with IPN.

New Model for Estimation of the Age at Onset in Spinocerebellar Ataxia Type 3.

Objectives: The aim of this study was to develop an appropriate parametric survival model to predict patient's age at onset (AAO) for spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) populations from mainland China.

Methods: We compared the efficiency and performance of 6 parametric survival analysis methods (exponential, weibull, log-gaussian, gaussian, log-logistic, and logistic) based on cytosine-adenine-guanine (CAG) repeat length at to predict the probability of AAO in the largest cohort of patients with SCA3/MJD. A set of evaluation criteria, including -2 log-likelihood statistic, Akaike information criterion (AIC), bayesian information criterion (BIC), Nagelkerke R-squared (Nagelkerke R^2), and Cox-Snell residual plot, were used to identify the best model.

Quantitative Histogram Analysis on Intracranial Atherosclerotic Plaques: A High-Resolution Magnetic Resonance Imaging Study.

Background And Purpose: Intracranial atherosclerosis is one of the main causes of stroke, and high-resolution magnetic resonance imaging provides useful imaging biomarkers related to the risk of ischemic events. This study aims to evaluate differences in histogram features between culprit and nonculprit intracranial atherosclerosis using high-resolution magnetic resonance imaging.

Methods: Two hundred forty-seven patients with intracranial atherosclerosis who underwent high-resolution magnetic resonance imaging sequentially between January 2015 and December 2016 were recruited.

A Single and Multiple Ascending Dose Study of Toll-Like Receptor 7 Agonist (RO7020531) in Chinese Healthy Volunteers.

Toll-like receptor 7 (TLR7) agonists modulate broad spectrum immune activity and are evaluated in the treatment of human diseases, including cancer and chronic viral infection. RO7020531, an oral prodrug of a TLR7 agonist, is in clinical development as part of a curative regimen against chronic hepatitis B. We report the safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of RO7020531 in healthy Chinese volunteers following single and multiple ascending doses (SAD and MAD).

Genome Sequencing Explores Complexity of Chromosomal Abnormalities in Recurrent Miscarriage.

Recurrent miscarriage (RM) affects millions of couples globally, and half of them have no demonstrated etiology. Genome sequencing (GS) is an enhanced and novel cytogenetic tool to define the contribution of chromosomal abnormalities in human diseases. In this study we evaluated its utility in RM-affected couples.

Robust CTCF-Based Chromatin Architecture Underpins Epigenetic Changes in the Heart Failure Stress-Gene Response.

Background: The human genome folds in 3 dimensions to form thousands of chromatin loops inside the nucleus, encasing genes and cis-regulatory elements for accurate gene expression control. Physical tethers of loops are anchored by the DNA-binding protein CTCF and the cohesin ring complex. Because heart failure is characterized by hallmark gene expression changes, it was recently reported that substantial CTCF-related chromatin reorganization underpins the myocardial stress-gene response, paralleled by chromatin domain boundary changes observed in CTCF knockout.

Facilitation of MrgprD by TRP-A1 promotes neuropathic pain.

Neuropathic pain remains a therapeutic challenge because of its complicated mechanisms. Mas-related GPCR D (MrgprD) is specifically expressed in small-diameter, nociceptive neurons of dorsal root ganglia (DRGs) and is implicated in pain modulation. However, the underlying mechanism of MrgprD involved in neuropathic pain remains elusive.

Buprenorphine Depresses Respiratory Variability in Obese Mice with Altered Leptin Signaling.

Background: Opiate-induced respiratory depression is sexually dimorphic and associated with increased risk among the obese. The mechanisms underlying these associations are unknown. The present study evaluated the two-tailed hypothesis that sex, leptin status, and obesity modulate buprenorphine-induced changes in breathing.

Lack of Remuscularization Following Transplantation of Human Embryonic Stem Cell-Derived Cardiovascular Progenitor Cells in Infarcted Nonhuman Primates.

Rationale: Human pluripotent stem cell-derived cardiovascular progenitor cells (hPSC-CVPCs) should be thoroughly investigated in large animal studies before testing in clinical trials.

Objective: The main of this study is to clarify whether hPSC-CVPCs can engraft for long time in the heart of primates after myocardial infarction (MI) and compare the effectiveness and safety of immunosuppression with cyclosporine alone or multiple-drug regimen (MDR) containing cyclosporine, methylprednisolone, and basiliximab in cynomolgus monkeys that had received intramyocardial injections of 1×10 EGFP (enhanced green fluorescent protein)-expressing hPSC-CVPCs after MI. A third group of animals received the immunosuppression MDR but without cell therapy after MI (MI+MDR group).

Identification and Quantitative Assessment of Different Components of Intracranial Atherosclerotic Plaque by Ex Vivo 3T High-Resolution Multicontrast MRI.

Background And Purpose: High-resolution 3T MR imaging can visualize intracranial atherosclerotic plaque. However, histologic validation is still lacking. This study aimed to evaluate the ability of 3T MR imaging to identify and quantitatively assess intracranial atherosclerotic plaque components ex vivo with histologic validation.

Single Locus Maintains Large Variation of Sex Reversal in Half-Smooth Tongue Sole ().

Sex determination is a fundamental biological process for individual sex development and population sex ratios. However, for some species, the primary sex might be altered during development, and individuals can develop into the opposite sex. Sex reversal may happen in insects, reptiles, amphibians, and fishes.

[Errors in six degree-of-freedom pose estimation of spine tumors assessed by image guided radiotherapy].

Objective: To evaluate the six-degree setup errors of tumors of cervical vertebra, thoracic vertebra and lumbar vertebra by image guided radiotherapy.

Methods: From May 2013 to June 2014, 30 patients with spinal malignant tumors(10 patients of cervical vertebra, thoracic vertebra and lumbar vertebra respectively) were treated with Elekata Synergy accelerator (Elekta company,Sweden). Six-degree set up errors were corrected using HexaPODTMevoRT bed under image of on board cone beam computed tomography (CBCT) guided.

Peroxisome Proliferator-Activated Receptor β/δ Alleviates Early Brain Injury After Subarachnoid Hemorrhage in Rats.

Background And Purpose: Early brain injury is proposed to be the primary cause of the poor outcome after subarachnoid hemorrhage (SAH), which is closely related to the neural apoptosis. To date, the relationship between peroxisome proliferator-activated receptor β/δ (PPARβ/δ) and nuclear factor-κB/matrix metalloproteinase-9 (NF-κB/MMP-9) pathway, both of which are closely related to apoptotic effects, has been poorly studied in SAH. The present study was undertaken to evaluate the effects of PPARβ/δ on early brain injury and NF-κB/MMP-9 pathway after SAH in rats.

[Assessments setup errors and target margin by 6D couch for primary cervical cancer].

Objective: To explore the inter and intra-fractional setup variations of HexaPOD evo RT 6-degree-of-freedom treatment couch plus kilovoltage (KV) cone-beam computed tomography (CBCT) in patients with primary cervical cancer and calculate the proper margins of CTV for clinical use.

Methods: From May 2013 to April 2014, 16 consecutive patients with primary cervical cancer were enrolled. Elekta AXESSE™ image guided radiation therapy (IGRT) modalities and vacuum pad were employed.

Medium modification of jet fragmentation in Au+Au collisions at √[s(NN)]=200 GeV measured in direct photon-hadron correlations.

The jet fragmentation function is measured with direct photon-hadron correlations in p+p and Au+Au collisions at √[s(NN)]=200 GeV. The p(T) of the photon is an excellent approximation to the initial p(T) of the jet and the ratio z(T)=p(T)(h)/p(T)(γ) is used as a proxy for the jet fragmentation function. A statistical subtraction is used to extract the direct photon-hadron yields in Au+Au collisions while a photon isolation cut is applied in p+p.