1008 Promotes Reproductive Function and Cognitive Activity in Aged Male Mice with High-Fat-Diet-Induced Obesity by Altering Metabolic Parameters and Alleviating Testicular Oxidative Damage, Inflammation and Apoptosis.

The effects of 1008 (LP1008) on age-related cognitive impairment and skeletal muscle atrophy have been reported previously. However, its role in obesity- and age-related hypogonadism has yet to be explored. This study investigates the therapeutic efficacy of low- and high-dose LP1008 in a high-fat-diet-fed male mouse model.

Discovery of Gene Fusions in Driver-Negative Cancer Samples From the National Cancer Institute-Molecular Analysis for Therapy Choice Screening Cohort.

Purpose: The National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) trial was implemented to identify actionable genetic alterations across cancer types and enroll patients accordingly onto treatment arms, irrespective of tumor histology. Using multiplex polymerase chain reaction (PCR) next-generation sequencing, NCI-MATCH genotyped 5,540 patients, discovering gene fusions in 202/5,540 tumors (3.65%).

Targeting GOF p53 and c-MYC through LZK Inhibition or Degradation Suppresses Head and Neck Tumor Growth.

The worldwide frequency of head and neck squamous cell carcinoma (HNSCC) is approximately 800,000 new cases, with 430,000 deaths annually. We determined that LZK (encoded by ) is a therapeutic target in HNSCC and showed that inhibition with small molecule inhibitors decreases the viability of HNSCC cells with amplified . A drug-resistant mutant of LZK blocks decreases in cell viability due to LZK inhibition, indicating on-target activity by two separate small molecules.

1008 Enhances Testicular Function and Spermatogenesis via the Modulation of Gut Microbiota in Male Mice with High-Fat-Diet-Induced Obesity.

Our study was designed to investigate the 1008 (LP1008) on testicular antioxidant capacity, spermatogenesis, apoptosis, autophagy, and metabolic function in male mice with high-fat-diet-induced obesity. A total of thirty-six male C57BL/6 mice were fed a normal diet (denoted as the NC group) or a high-fat control diet (denoted as the HFC group) for 16 weeks, then half of the HFC group was randomly chosen and subsequently fed with LP1008 for the final 8 weeks (high-fat diet + LP1008; denoted as the HFP group). The HFP group expressed improved blood cholesterol, insulin resistance, hepatic function, and lipopolysaccharide (LPS) levels compared to the HFC group.

Hirsutella sinensis intensifies testicular function and spermatogenesis in male mice with high-fat diet-induced obesity.

Background: Hirsutella sinensis (HS) is a mycelium isolated from the fruiting body of the medicinal mushroom Cordyceps sinensis . This study explored whether HS treatment affects reproductive dysfunction in a high-fat diet (HFD)-induced mouse model and regulates various mechanisms, focusing on oxidative stress, apoptosis, inflammation, and autophagy.

Methods: Twenty-four C57BL/6J (B6) mice were randomly divided into a standard chow diet (NCD)- or HFD-fed group for 24 weeks.

The intervention of artificial intelligence to improve the weaning outcomes of patients with mechanical ventilation: Practical applications in the medical intensive care unit and the COVID-19 intensive care unit: A retrospective study.

Patients admitted to intensive care units (ICU) and receiving mechanical ventilation (MV) may experience ventilator-associated adverse events and have prolonged ICU length of stay (LOS). We conducted a survey on adult patients in the medical ICU requiring MV. Utilizing big data and artificial intelligence (AI)/machine learning, we developed a predictive model to determine the optimal timing for weaning success, defined as no reintubation within 48 hours.

Assessing the diversity and determinants of health-related quality of life measures in patients with acute heart failure.

Aims: Heart failure with reduced ejection fraction (HFrEF) significantly impacts health-related quality of life (HR-QoL). Existing HR-QoL questionnaires can show inconsistencies, potentially misrepresenting patient self-reports. This study examines the variation in HR-QoL measurement tools for HFrEF patients, identifying related determinants.

Pharmacodynamic effects of the PARP inhibitor talazoparib (MDV3800, BMN 673) in patients with BRCA-mutated advanced solid tumors.

Purpose: Talazoparib is an inhibitor of the poly (ADP-ribose) polymerase (PARP) family of enzymes and is FDA-approved for patients with (suspected) deleterious germline BRCA1/2-mutated, HER2‑negative, locally advanced or metastatic breast cancer. Because knowledge of the pharmacodynamic (PD) effects of talazoparib in patients has been limited to studies of PARP enzymatic activity (PARylation) in peripheral blood mononuclear cells, we developed a study to assess tumoral PD response to talazoparib treatment (NCT01989546).

Methods: We administered single-agent talazoparib (1 mg/day) orally in 28-day cycles to adult patients with advanced solid tumors harboring (suspected) deleterious BRCA1 or BRCA2 mutations.

Spatial variability of nitrogen cycling in the sediments of the Danshuie River Estuary (Northern Taiwan).

Dissolved N species, TOC and total N (TN) in sediment cores (SC) collected from an eutrophic estuary were analyzed to understand the N geochemical variation in SC of the eutrophic estuary. Extremely higher concentrations of ammonium (6550 μM) and DON (2050 μM) were observed in pore water of the upper estuary and both concentrations generally accounted for 65-99 % and 1-34 % of the dissolved total N pool, respectively, in the three sediment pore waters. The DON and TN concentrations decreased with increasing depth in SC of the upper estuary, opposite the ammonium profile, suggesting that the mineralization of DON and TN provided the ammonium source to the SC.

Aspergillus coinfection in critically Ill patients with severe dengue.

In 2014-2015, a significant outbreak of dengue fever occurred in southern Taiwan, with a subsequent decline in dengue incidence. Despite this, there is emerging concern about virus-associated aspergillosis, yet limited research has explored coinfections involving dengue and aspergillosis. We conducted a retrospective study at a single center in Southern Taiwan, specifically focusing on dengue patients admitted to the intensive care unit during the period between July and November 2015.

Assessment of Tyrosine Kinase Inhibitors and Survival and Cardiovascular Outcomes of Patients With Non-Small Cell Lung Cancer in Taiwan.

Importance: Tyrosine kinase inhibitors (TKIs) have been recognized as the standard treatment for patients with non-small cell lung cancers (NSCLCs) and epidermal growth factor receptor (EGFR) sequence variation. Although TKIs have been reported to cause cardiotoxicity, they are widely administered owing to the high prevalence of EGFR sequence variation in Taiwan.

Objective: To compare the outcomes of death and major adverse cardiac and cerebrovascular events among patients with NSCLC who use and do not use TKIs in a national cohort.

The association between tyrosine kinase inhibitors and fatal arrhythmia in patients with non-small cell lung cancer in Taiwan.

Objective: As a standard therapy, tyrosine kinase inhibitors (TKIs) improved survival in patients with non-small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutation. However, treatment-related cardiotoxicity, particularly arrhythmia, cannot be ignored. With the prevalence of EGFR mutations in Asian populations, the risk of arrhythmia among patients with NSCLC remains unclear.

Comparison of the risk of gastrointestinal perforation between patients with and without rheumatoid arthritis: A nationwide cohort study in Asia.

Objectives: Patients with rheumatoid arthritis (RA) may have an increased risk for gastrointestinal perforation (GIP) caused by medications or chronic inflammation. However, the risk of GIP between patients with and without RA remains unclear. Therefore, we conducted this study to clarify it.

Curcumin Remedies Testicular Function and Spermatogenesis in Male Mice with Low-Carbohydrate-Diet-Induced Metabolic Dysfunction.

Increasing reports on the significance of dietary patterns in reproduction have arisen from both animal and human studies, suggesting an interactive association between nutrition and male fertility. The aim of this study was to investigate the effects of curcumin supplementation on low-carbohydrate-diet-induced metabolic dysfunction, testicular antioxidant capacity, apoptosis, inflammation and spermatogenesis in male mice. Male C57BL/6 mice were fed a normal diet (AIN-93M group, n = 12) and a low-carbohydrate diet for 12 weeks (LC group, fed with low-carbohydrate diet, n = 48), and mice randomly chosen from the LC group were later fed their original diet (LC group, n = 12).

Effects of Iron Supplementation on Testicular Function and Spermatogenesis of Iron-Deficient Rats.

Iron deficiency is the most common micronutrient deficiency in the world. Previous studies have shown that iron deficiency increases oxidative stress and decreases antioxidant enzymes, and studies of male infertility indicated that oxidative stress may affect male reproductive functions. The aim of this study was to investigate the effects of iron supplementation on spermatogenesis and testicular functions in iron-deficient rats.

Risk factors for reintubation and mortality among patients who had unplanned extubation.

Background: Unplanned extubation (UE) occurs among 2%-16% of patients with mechanical ventilation (MV). Failed UE requiring reintubation could be associated with several adverse events.

Aims: The aim of this study was to investigate the outcomes and prognostic factors of patients with UE in intensive care units (ICUs).

Is a Ketogenic Diet Superior to a High-Fat, High-Cholesterol Diet Regarding Testicular Function and Spermatogenesis?

The study aimed to determine effects of a ketogenic diet on metabolic dysfunction, testicular antioxidant capacity, apoptosis, inflammation, and spermatogenesis in a high-fat and high-cholesterol diet-induced obese mice model. Forty-two male C57BL/6 mice were fed either a normal diet (NC group) or a high-fat and high-cholesterol (HFC) diet (HFC group) for 16 weeks, and mice from the HFC group were later randomly divided into two groups: the first were maintained on the original HFC diet, and the second were fed a medium-chain triacylglycerol (MCT)-based ketogenic diet for 8 weeks (KD group). A poor semen quality was observed in the HFC group, but this was eliminated by the ketogenic diet.

Does Coenzyme Q10 Supplementation Improve Testicular Function and Spermatogenesis in Male Mice with Chronic Kidney Disease?

The aim of the study was to examine the potential effects of coenzyme Q10 (CoQ10) on reproductive function in a chronic kidney disease (CKD) mouse model. Nine-week-old mice were randomly assigned to two groups: sham surgery ( = 18) and CKD surgery ( = 18). After surgery, the study groups received CoQ10 (10 mg/kg body weight dissolved in corn oil by oral gavage) or corn oil as a vehicle daily for 8 weeks.

Safety, Antitumor Activity, and Biomarker Analysis in a Phase I Trial of the Once-daily Wee1 Inhibitor Adavosertib (AZD1775) in Patients with Advanced Solid Tumors.

Purpose: The Wee1 kinase inhibitor adavosertib abrogates cell-cycle arrest, leading to cell death. Prior testing of twice-daily adavosertib in patients with advanced solid tumors determined the recommended phase II dose (RPh2D). Here, we report results for once-daily adavosertib.

A High Phosphorus Diet Impairs Testicular Function and Spermatogenesis in Male Mice with Chronic Kidney Disease.

Hyperphosphatemia is a serious complication in chronic kidney disease (CKD) that occurs due to insufficient excretion of phosphorus during failure of renal function. Both CKD and an excessive phosphorus intake have been reported to increase oxidative stress and result in poor male fertility, but little is known about the reproductive function of the CKD under a poorly controlled phosphate intake. Eight-week-old C57BL/6 mice ( = 66) were randomly divided into four groups: a sham operation group received a chow diet as control (SC group, = 14), CKD-induced mice received a chow diet (CKDC group, = 16), control mice received a high phosphorus (HP) diet (SP group, = 16), and CKD-induced mice received a HP diet (CKDP group, = 20).

Metformin Ameliorates Testicular Function and Spermatogenesis in Male Mice with High-Fat and High-Cholesterol Diet-Induced Obesity.

The aim of this study was to investigate the effects of metformin supplementation on metabolic dysfunction, testicular antioxidant capacity, apoptosis, inflammation and spermatogenesis in male mice with high-fat and high-cholesterol diet-induced obesity. Forty male C57BL/6 mice were fed a normal diet (NC group, = 10) or a high-fat and high-cholesterol diet (HFC group, = 30) for 24 weeks, and mice randomly chosen from the HFC group were later treated with metformin for the final 8 weeks of HFC feeding (HFC + Met group, = 15). Compared with the HFC group, the obese mice supplemented with metformin exhibited improved blood cholesterol, glucose and insulin resistance.

Multi-Access Networking with Wireless Ultrasound-Powered Implants.

Multi-access networking with miniaturized wireless implantable devices can enable and advance closed-loop medical applications to deliver precise diagnosis and treatment. Using ultrasound (US) for wireless implant systems is an advantageous approach as US can beamform with high spatial resolution to efficiently power and address multiple implants in the network. To demonstrate these capabilities, we use wirelessly powered mm-sized implants with bidirectional communication links; uplink data communication measurements are performed using time, spatial, and frequency-division multiplexing schemes in tissue phantom.

Ultrasonic Implant Localization for Wireless Power Transfer: Active Uplink and Harmonic Backscatter.

Efficient ultrasonic power transfer to implantable devices requires precise transmitter beamforming to the receiver and can quickly degrade with small changes in implant location. Ultrasound localization can be used to find and track implants in the body to maintain an efficient link. We present a framework to calculate localization accuracy showing that sub-mm accuracy is obtainable using only three receive channels.

Assessment of miniaturized ultrasound-powered implants: an in vivo study.

Objective: Therapeutic applications of implantable active medical devices have improved the quality of patient life. Numerous on-going research in the field of neuromodulation and bioelectronic medicine are exploring the use of these implants for treating diseases and conditions. Miniaturized implantable medical devices that are wirelessly powered by ultrasound (US) can be placed close to the target sites deep inside the body for effective therapy with less invasiveness.