UDA-seq: universal droplet microfluidics-based combinatorial indexing for massive-scale multimodal single-cell sequencing.

The use of single-cell combinatorial indexing sequencing via droplet microfluidics presents an attractive approach for balancing cost, scalability, robustness and accessibility. However, existing methods often require tailored protocols for individual modalities, limiting their automation potential and clinical applicability. To address this, we introduce UDA-seq, a universal workflow that integrates a post-indexing step to enhance throughput and systematically adapt existing droplet-based single-cell multimodal methods.

Novel Biallelic Synonymous Exonic Variant in Affecting mRNA Splicing: Case Report.

Objectives: Chorea-acanthocytosis is an autosomal recessively inherited condition caused by loss-of-function pathogenic variants in . We identified a novel synonymous exonic variant leading to abnormal mRNA splicing in a patient with chorea-acanthocytosis.

Methods: A patient with focal epilepsy developed generalized chorea with orolingual dystonia, cognitive decline, and peripheral neuropathy, consistent with chorea-acanthocytosis.

Efficacy and safety of JMT103 in patients with unresectable or surgically-challenging giant cell tumor of bone: a multicenter, phase Ib/II study.

This was a multicenter, single-arm, open-label, phase Ib/II study (NCT04255576), aimed to evaluate the efficacy and safety of JMT103 in patients with unresectable or surgically-challenging giant cell tumor of bone (GCTB). JMT103 (2 mg/kg) was administered subcutaneously every four weeks, with loading doses on days 8 and 15. The primary endpoint was the objective tumor response rate (OTR) based on best response, defined as the proportion of patients who achieved elimination of at least 90% of the giant cells or radiologic complete or partial response per the modified Inverse Choi density/size (mICDS) or modified European Organization for Research and Treatment of Cancer (mEORTC) within 12 weeks.

Composite Hedges Nanopores codec system for rapid and portable DNA data readout with high INDEL-Correction.

Reading digital information from highly dense but lightweight DNA medium nowadays relies on time-consuming next-generation sequencing. Nanopore sequencing holds the promise to overcome the efficiency problem, but high indel error rates lead to the requirement of large amount of high quality data for accurate readout. Here we introduce Composite Hedges Nanopores, capable of handling indel rates up to 15.

The Protective Efficacy of a SARS-CoV-2 Vaccine Candidate B.1.351V against Several Variant Challenges in K18-hACE2 Mice.

The emergence of SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and partial resistance to neutralization by antibodies has been observed globally. There is an urgent need for an effective vaccine to combat these variants. Our study demonstrated that the B.

Targeting Neuronal GPR65 With Delayed BTB09089 Treatment Improves Neurorehabilitation Following Ischemic Stroke.

Background: GPR65 (G protein-coupled receptor 65) can sense extracellular acidic environment to regulate pathophysiological processes. Pretreatment with the GPR65 agonist BTB09089 has been proven to produce neuroprotection in acute ischemic stroke. However, whether delayed BTB09089 treatment and neuronal GPR65 activation promote neurorestoration remains unknown.

Copper-Induced In Vivo Gene Amplification in Budding Yeast.

In the biotechnological industry, multicopy gene integration represents an effective strategy to maintain a high-level production of recombinant proteins and to assemble multigene biochemical pathways. In this study, we developed copper-induced in vivo gene amplification in budding yeast for multicopy gene expressions. To make copper as an effective selection pressure, we first constructed a copper-sensitive yeast strain by deleting the gene encoding a small metallothionein-like protein for copper resistance.

A Least Absolute Shrinkage and Selection Operator-Derived Predictive Model for Postoperative Respiratory Failure in a Heterogeneous Adult Elective Surgery Patient Population.

Background: Postoperative respiratory failure (PRF) is associated with increased hospital charges and worse patient outcomes. Reliable prediction models can help to guide postoperative planning to optimize care, to guide resource allocation, and to foster shared decision-making with patients.

Research Question: Can a predictive model be developed to accurately identify patients at high risk of PRF?

Study Design And Methods: In this single-site proof-of-concept study, we used structured query language to extract, transform, and load electronic health record data from 23,999 consecutive adult patients admitted for elective surgery (2014-2021).

Deep self-learning enables fast, high-fidelity isotropic resolution restoration for volumetric fluorescence microscopy.

One intrinsic yet critical issue that troubles the field of fluorescence microscopy ever since its introduction is the unmatched resolution in the lateral and axial directions (i.e., resolution anisotropy), which severely deteriorates the quality, reconstruction, and analysis of 3D volume images.

Bestrophin3 Deficiency in Vascular Smooth Muscle Cells Activates MEKK2/3-MAPK Signaling to Trigger Spontaneous Aortic Dissection.

Background: Aortic dissection (AD) is a fatal cardiovascular disorder without effective medications due to unclear pathogenic mechanisms. Bestrophin3 (Best3), the predominant isoform of bestrophin family in vessels, has emerged as critical for vascular pathological processes. However, the contribution of Best3 to vascular diseases remains elusive.

Association of Procedure Time With Clinical and Procedural Outcome in Patients With Basilar Occlusion Undergoing Embolectomy.

Background And Objectives: Previous studies have demonstrated the association between the procedure time (PT) and outcomes for patients with proximal large vessel occlusion; however, whether the relationship remains for patients with acute basilar artery occlusion (ABAO) was not clear. We aimed to characterize the association between PT and other procedure-related variables on clinical outcomes among patients with ABAO who underwent endovascular treatment (EVT).

Methods: Patients with ABAO who underwent EVT with a documented PT in the EVT for Acute Basilar Artery Occlusion (BASILAR) study from January 2014 to May 2019 among 47 comprehensive centers in China were included.

Development of Expert-Level Classification of Seizures and Rhythmic and Periodic Patterns During EEG Interpretation.

Background And Objectives: Seizures (SZs) and other SZ-like patterns of brain activity can harm the brain and contribute to in-hospital death, particularly when prolonged. However, experts qualified to interpret EEG data are scarce. Prior attempts to automate this task have been limited by small or inadequately labeled samples and have not convincingly demonstrated generalizable expert-level performance.

Interrater Reliability of Expert Electroencephalographers Identifying Seizures and Rhythmic and Periodic Patterns in EEGs.

Background And Objectives: The validity of brain monitoring using electroencephalography (EEG), particularly to guide care in patients with acute or critical illness, requires that experts can reliably identify seizures and other potentially harmful rhythmic and periodic brain activity, collectively referred to as "ictal-interictal-injury continuum" (IIIC). Previous interrater reliability (IRR) studies are limited by small samples and selection bias. This study was conducted to assess the reliability of experts in identifying IIIC.

Neuroprotective Effects of Transferrin in Experimental Glaucoma Models.

Iron is essential for retinal metabolism, but an excess of ferrous iron causes oxidative stress. In glaucomatous eyes, retinal ganglion cell (RGC) death has been associated with dysregulation of iron homeostasis. Transferrin (TF) is an endogenous iron transporter that controls ocular iron levels.

Chronic Treatment With WY-14643 Induces Tumorigenesis and Triglyceride Accumulation in Mouse Livers.

Peroxisome proliferator-activated receptor (PPAR) is closely related to lipid metabolism and various liver diseases. Previous study has shown that chronic treatment with PPAR agonist WY-14643 can induce liver tumors in rodents, but the implications of this process on lipid metabolism in the liver remain unclear. Thus, this study aimed to explore the influences of chronic treatment with WY-14643 on the liver and hepatic lipid metabolism.

Circulating monocytes associated with anti-PD-1 resistance in human biliary cancer induce T cell paralysis.

Suppressive myeloid cells can contribute to immunotherapy resistance, but their role in response to checkpoint inhibition (CPI) in anti-PD-1 refractory cancers, such as biliary tract cancer (BTC), remains elusive. We use multiplexed single-cell transcriptomic and epitope sequencing to profile greater than 200,000 peripheral blood mononuclear cells from advanced BTC patients (n = 9) and matched healthy donors (n = 8). Following anti-PD-1 treatment, CD14 monocytes expressing high levels of immunosuppressive cytokines and chemotactic molecules (CD14) increase in the circulation of patients with BTC tumors that are CPI resistant.

Integrating deep learning and unbiased automated high-content screening to identify complex disease signatures in human fibroblasts.

Drug discovery for diseases such as Parkinson's disease are impeded by the lack of screenable cellular phenotypes. We present an unbiased phenotypic profiling platform that combines automated cell culture, high-content imaging, Cell Painting, and deep learning. We applied this platform to primary fibroblasts from 91 Parkinson's disease patients and matched healthy controls, creating the largest publicly available Cell Painting image dataset to date at 48 terabytes.

Clinical and biomarker analyses of sintilimab versus chemotherapy as second-line therapy for advanced or metastatic esophageal squamous cell carcinoma: a randomized, open-label phase 2 study (ORIENT-2).

This randomized, open-label, multi-center phase 2 study (NCT03116152) assessed sintilimab, a PD-1 inhibitor, versus chemotherapy in patients with esophageal squamous cell carcinoma after first-line chemotherapy. The primary endpoint was overall survival (OS), while exploratory endpoint was the association of biomarkers with efficacy. The median OS in the sintilimab group was significantly improved compared with the chemotherapy group (median OS 7.

Contemporary Update of Retinoblastoma in China: Three-Decade Changes in Epidemiology, Clinical Features, Treatments, and Outcomes.

Purpose: To report three-decade changes of clinical characteristics, progress of treatments, and risk factors associated with mortality and enucleation in patients with retinoblastoma in China.

Design: Retrospective cohort study.

Methods: This multicenter study included 2552 patients diagnosed with retinoblastoma in 38 medical centers in 31 provinces in China from 1989 to 2017, with follow-up data.

Precision vibratome for high-speed ultrathin biotissue cutting and organ-wide imaging.

Cutting tissues into ultrathin slices is highly desired in sectioning-based organ-wide imaging. However, it is difficult to perform tissue cutting at a high speed with excellent quality. Here, we design a precision vibratome based on a paired double parallelogram flexure, which enables a vibrating blade to move strictly along a straight line.

Deciphering Neurodegenerative Diseases Using Long-Read Sequencing.

Neurodegenerative diseases exhibit chronic progressive lesions in the central and peripheral nervous systems with unclear causes. The search for pathogenic mutations in human neurodegenerative diseases has benefited from massively parallel short-read sequencers. However, genomic regions, including repetitive elements, especially with high/low GC content, are far beyond the capability of conventional approaches.

No Associations Between Regular Use of Proton Pump Inhibitors and Risk of All-Cause and Cause-Specific Mortality: A Population-Based Cohort of 0.44 Million Participants.

Introduction: The association between proton pump inhibitors' (PPIs) use and mortality remains unclear.

Methods: This was a prospective analysis of 440,840 UK residents and 13,154 deaths. We evaluated the associations with multivariate Cox regression.

A safe and effective mucosal RSV vaccine in mice consisting of RSV phosphoprotein and flagellin variant.

Respiratory syncytial virus (RSV) is a major cause of serious acute lower respiratory tract infection in infants and the elderly. The lack of a licensed RSV vaccine calls for the development of vaccines with other targets and vaccination strategies. Here, we construct a recombinant protein, designated P-KFD1, comprising RSV phosphoprotein (P) and the E.