Nonviral targeted mRNA delivery: principles, progresses, and challenges.

Messenger RNA (mRNA) therapeutics have garnered considerable attention due to their remarkable efficacy in the treatment of various diseases. The COVID-19 mRNA vaccine and RSV mRNA vaccine have been approved on the market. Due to the inherent nuclease-instability and negative charge of mRNA, delivery systems are developed to protect the mRNA from degradation and facilitate its crossing cell membrane to express functional proteins or peptides in the cytoplasm.

Second-line therapies in advanced hepatocellular carcinoma following first-line atezolizumab and bevacizumab: multicenter single institution cohort experience.

Background: Atezolizumab plus bevacizumab (A/B) received FDA approval as the first-line therapy for patients with advanced hepatocellular carcinoma (HCC) in 2020. However, optimal subsequent treatment options are unclear. Here, we describe clinical outcomes of advanced HCC patients following first-line treatment with A/B.

Beta oscillation modulations of the orienting attention network effect correlate with dopamine-dependent motor symptoms of Parkinson's disease.

Attention impairment, a prevalent non-motor symptom in Parkinson's disease (PD), plays a crucial role in movement disorders. PD patients exhibit abnormalities in the attentional network related to alerting, orienting, and executive control. While dopamine medications have well-documented effects on motor function, their impact on attention networks and the underlying neural mechanisms involved in motor functions remain unclear.

Exploring the link between dietary thiamine and type 2 diabetes mellitus risk in US adults aged 45 years and older: Insights from a cross-sectional investigation.

The correlation between dietary thiamine intake and the incidence of type 2 diabetes mellitus (T2DM) remains a subject of controversy within the academic community. While numerous studies have attempted to elucidate this relationship, conclusive evidence remains elusive. A survey of U.

Customizing Bonding Affinity with Multi-Intermediates via Interfacial Electron Capture to Boost Hydrogen Evolution in Alkaline Water Electrolysis.

Developing efficient and earth-abundant alkaline HER electrocatalysts is pivotal for sustainable energy, but co-regulating its intricate multi-step process, encompassing water dissociation, OH desorption, and hydrogen generation, is still a great challenge. Herein, we tackle these obstacles by fabricating a vertically integrated electrode featuring a nanosheet array with prominent dual-nitride metallic heterostructures characterized by impeccable lattice matching and excellent conductivity, functioning as a multi-purpose catalyst to fine-tune the bonding affinity with alkaline HER intermediates. Detailed structural characterization and theoretical calculation elucidate that charge redistribution at the heterointerface reduces the O p-W d and H s-W d interactions vs.

Rehabilitation Response in Tremor- and Non-Tremor-Dominant Parkinson Disease: A Task-fMRI Study.

Background: Tremor-dominant (TD) and nontremor-dominant (NTD) Parkinson's disease (PD) showed different responses to rehabilitation. However, the neural mechanism behind this remains unclear.

Methods: This cohort study explores changes in motor function, brain activation, and functional connectivity following 2 weeks of rehabilitation in TD-PD and NTD-PD patients, respectively.

Analysis of the ideal cutoff age as a predictor of differentiated thyroid cancer using the Surveillance, Epidemiology, and End Results database.

Background: It has been discovered that the prognosis of patients with differentiated thyroid cancer (DTC) correlates with age at initial diagnosis. However, there are disagreements over the optimal cutoff age among the numerous staging and risk stratification criteria, which make it inconsistent to predict the clinical prognosis of specific DTC patients. This study aimed to determine the optimum cutoff age for diagnosis in relation to the clinical outcomes of DTC using data from the Surveillance, Epidemiology and End Results (SEER) database.

Impact of proton pump inhibitors on pathologic response rates following fluoropyrimidine-based neoadjuvant chemotherapy in pancreatic cancer patients.

Background: Proton pump inhibitors (PPIs) negatively impact fluoropyrimidine-based chemotherapy efficacy in colorectal cancer. This study assessed PPI impact on major pathologic response (mPR) rates of pancreatic adenocarcinoma (PDAC) patients receiving fluoropyrimidine-based chemotherapy.

Methods: An institutional retrospective review of resected PDAC patients receiving neoadjuvant fluoropyrimidine-based chemotherapy (98% FOLFIRINOX) from 2011 to 2021 was conducted.

Circulating Tumor DNA Predicts Early Recurrence Following Locoregional Therapy for Oligometastatic Colorectal Cancer.

(1) Background: Local therapies offer a potentially curative approach for patients with oligometastatic colorectal cancer (CRC). An evidence-based consensus recommendation for systemic therapy following definitive locoregional therapy is lacking. Tumor-informed circulating tumor DNA (ctDNA) might provide information to help guide management in this setting.

A model for identifying potentially inappropriate medication used in older people with dementia: a machine learning study.

Background: Older adults with dementia often face the risk of potentially inappropriate medication (PIM) use. The quality of PIM evaluation is hindered by researchers' unfamiliarity with evaluation criteria for inappropriate drug use. While traditional machine learning algorithms can enhance evaluation quality, they struggle with the multilabel nature of prescription data.

Atezolizumab plus bevacizumab as first-line systemic therapy for hepatocellular carcinoma: a multi-institutional cohort study.

Background: Atezolizumab plus bevacizumab is the standard of care for advanced hepatocellular carcinoma (HCC) in the first-line setting, although was only evaluated in patients with Child-Pugh (CP) A liver function in the IMbrave150 trial. We sought to determine the outcomes of these patients based on CP score and ALBI grade in the US population.

Methods: This multicenter cohort study included patients with HCC who received atezolizumab with bevacizumab as first-line systemic therapy between March 2018 and November 2023.

A gelatin-based ionogel with anti-swelling properties for underwater human physiological signal detection.

A hydrogel is an ideal matrix material for flexible electronic devices, electronic skin and health detection devices due to its outstanding flexibility and stretchability. However, hydrogel-based flexible electronic devices swell once they are placed in a high humidity or underwater environment. The swelling behavior could damage the internal structure of hydrogels, ultimately leading to the reduction or complete loss of mechanical properties, electrical conductivity and sensing function.

ctDNA as a predictor of outcome after curative resection for locally advanced rectal cancer: systematic review and meta-analysis.

Aim: To assess the efficacy of ctDNA measurement at different time intervals in predicting response and prognosis in patients diagnosed with locally advanced rectal cancer (LARC) who underwent neoadjuvant treatment prior to curative resection.

Method: English language randomized controlled trials and observational studies, published from 1946 to January 2024, comparing outcomes between ctDNA-positive and ctDNA-negative patients with LARC undergoing neoadjuvant treatment prior to curative surgical resection were included in the search. The search included Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and the Cochrane Database of Systematic Reviews (CDSR).

Frequency of Common and Uncommon Alterations among Colorectal and Non-Colorectal Gastrointestinal Malignancies.

Background: The predictive and prognostic role of alterations has been evaluated in colorectal cancer (CRC); however, alterations have not been fully characterized in non-CRC gastrointestinal (GI) malignancies. In the present study, we report the frequency and spectrum of alterations among patients with non-CRC GI malignancies.

Methods: Patients with CRC and non-CRC GI malignancies who underwent somatic tumor profiling via a tissue-based or liquid-based assay were included in this study.

Updates on the Management of Colorectal Cancer in Older Adults.

Colorectal cancer (CRC) poses a significant global health challenge. Notably, the risk of CRC escalates with age, with the majority of cases occurring in those over the age of 65. Despite recent progress in tailoring treatments for early and advanced CRC, there is a lack of prospective data to guide the management of older patients, who are frequently underrepresented in clinical trials.

Evaluating the Therapeutic Potential of Durvalumab in Adults with Locally Advanced or Metastatic Biliary Tract Cancer: Evidence to Date.

Advanced biliary tract cancers (BTCs) have historically been managed with chemotherapy but, in recent years, this treatment paradigm has begun to shift with the introduction of immune checkpoint inhibitors in addition to standard of care chemotherapy. The tumor microenvironment of BTC may be enriched with regulatory T lymphocytes and immune checkpoint expression in some patients. Durvalumab, an anti-programmed death ligand-1 (PD-L1) antibody, in combination with gemcitabine and cisplatin, has now received United States Food and Drug Administration approval for treatment of advanced BTC.

Association between dietary fiber intake and diabetic nephropathy among adult diabetes mellitus in the United States: A cross-sectional study.

Objective: There has been some evidence that dietary fiber may be associated with diabetic nephropathy (DN), but the relationship is still unclear. The purpose of this study was to examine the association between dietary fiber intake and DN.

Methods: This cross-sectional study used National Health and Nutrition Examination Survey (NHANES) data collected between 2007 and 2020.

Functional and structural gradients reveal atypical hierarchical organization of Parkinson's disease.

Parkinson's disease (PD) patients exhibit deficits in primary sensorimotor and higher-order executive functions. The gradient reflects the functional spectrum in sensorimotor-associated areas of the brain. We aimed to determine whether the gradient is disrupted in PD patients and how this disruption is associated with treatment outcome.

Comparison of different rhythmic auditory stimuli on prefrontal cortex cortical activation during upper limb movement in patients with Parkinson's disease: a functional near-infrared spectroscopy study.

Background: A large number of literatures show that rhythmic auditory stimulation (RAS) can effectively improve Parkinson's disease (PD) patients' gait speed, frequency and speed. Its application and curative effect on upper limb motor function is relatively few.

Objective: By studying the immediate effect of RAS with different rhythms on the prefrontal cortex (PFC) blood oxygen response during upper limb movement in PD patients, this study discusses the potential neurophysiological mechanism of RAS on upper limb movement in PD patients, which is expected to provide guidance for patients with upper limb dysfunction such as Parkinson's disease.

Projected Incidence of Hepatobiliary Cancers and Trends Based on Age, Race, and Gender in the United States.

Background: Identifying the projected incidence of hepatobiliary cancers and recognizing patient cohorts at increased risk can help develop targeted interventions and resource allocation. The expected incidence of subtypes of hepatobiliary cancers in different age groups, races, and genders remains unknown.

Methods: Historical epidemiological data from the Surveillance, Epidemiology, and End Results (SEER) database was used to project future incidence of hepatobiliary malignancies in the United States and identify trends by age, race, and gender.

Association between autonomic dysfunction with motor and non-motor symptoms in patients with Parkinson's disease.

To investigate the association between autonomic dysfunction (AutD) and motor as well as non-motor symptoms (NMS) in patients with Parkinson's disease (PD). Fifty-three PD patients were divided into two groups based on the number of domains affected by AutD: a multi-domain AutD group (AutD-M) and a single-domain AutD group (AutD-S), as evaluated using the Scale for Outcomes in Parkinson's disease-Autonomic (SCOPA-AUT), which assesses autonomic symptoms, one of the NMS. A comprehensive comparison was conducted between the two groups, including clinical measures such as clinical scales, quantitative evaluations of motor function and exercise capacity.

Tumor-Informed Circulating Tumor DNA for Minimal Residual Disease Detection in the Management of Colorectal Cancer.

Purpose: Recurrence after curative-intent treatment occurs in 20%-50% of patients with stage II-IV colorectal cancer (CRC), underscoring the need for early detection of minimal residual disease (MRD) using circulating tumor DNA (ctDNA). Here, we examined the pattern of use of a tumor-informed ctDNA assay in CRC MRD monitoring in routine clinical practice at Mayo Clinic, Rochester.

Methods: We conducted a retrospective analysis of health records of patients with CRC who had at least one tumor-informed ctDNA assay from May 2019 through July 1, 2022.

Hyperglycemia affects axial signs in patients with Parkinson's disease through mechanisms of insulin resistance or non-insulin resistance.

Objective: To investigate the influence of hyperglycemia on motor symptoms, especially axial signs, and potential mechanisms related to insulin resistance (IR) in patients with Parkinson's disease (PWP).

Methods: According to glycated hemoglobin (HbA1c) level, PWP were divided into the low-HbA1c and the high-HbA1c groups. Demographic information, glucose metabolism-related variables, Hoehn-Yahr stage, and motor function were compared between the two groups.