Ultra-large scale virtual screening identifies a small molecule inhibitor of the Wnt transporter Wntless.

Wnts are lipid-modified glycoproteins that play key roles in both embryonic development and adult homeostasis. Wnt signaling is dysregulated in many cancers and preclinical data shows that targeting Wnt biosynthesis and secretion can be effective in Wnt-addicted cancers. An integral membrane protein known as Wntless (WLS/Evi) is essential for Wnt secretion.

Low-to-Moderate Arsenic Exposure and Urothelial Tract Cancers with a Long Latent Period of Follow-Up in an Arseniasis Area.

Background: Arsenic exposure can cause adverse health effects. The effects of long-term low-to-moderate exposure and methylations remain unclear.

Objective: This study aims to examine the association between low-to-moderate arsenic exposure and urothelial tract cancers while considering the effects of methylation capacity.

Kinship analysis of type 2 diabetes mellitus familial aggregation in Taiwan.

Background: Family disease history plays a vital role in type 2 diabetes mellitus (T2DM) risk. However, the familial aggregation of T2DM among different kinship relatives warrants further investigation.

Methods: This nationwide kinship relationship study collected 2000-2016 data of two to five generations of the Taiwanese population from the National Health Insurance Research Database.

Structural model of human PORCN illuminates disease-associated variants and drug-binding sites.

Wnt signaling is essential for normal development and is a therapeutic target in cancer. The enzyme PORCN, or porcupine, is a membrane-bound O-acyltransferase (MBOAT) that is required for the post-translational modification of all Wnts, adding an essential mono-unsaturated palmitoleic acid to a serine on the tip of Wnt hairpin 2. Inherited mutations in PORCN cause focal dermal hypoplasia, and therapeutic inhibition of PORCN slows the growth of Wnt-dependent cancers.

Higher Leptin-to-Adiponectin Ratio Strengthens the Association Between Body Measurements and Occurrence of Type 2 Diabetes Mellitus.

This case-control study aimed to investigate the interrelations of body measurements and selected biomarkers in type 2 diabetes mellitus (T2DM). We recruited 98 patients with T2DM and 98 controls from 2016 to 2018 in Taiwan. Body measurements were obtained using a three-dimensional body surface scanning system.

Combination of Thigh Circumference and Indices of Central Obesity Helps Predict Incident Chronic Kidney Disease: A 14-Year Prospective Cohort Study Using a Three-Dimensional Body Laser Scanner.

Objective: Obesity, high body mass index, and visceral fat accumulation are associated with renal diseases. However, the association between body measurements and chronic kidney disease (CKD) is still unclear.

Methods: A cohort of 7,825 participants scheduled for follow-up of CKD was recruited from 2000 to 2008 in Taiwan.

Adverse body measurements are superior to sarcopenia-associated measurements in predicting chronic diseases.

Few studies have demonstrated an association of sarcopenia-associated body measurements with chronic diseases through a comprehensive methodology. This study aims to examine the relationship between sarcopenia-associated body measurements and chronic diseases. This is a cohort study.

Joint effects of genomic markers and urinary methylation capacity associated with inorganic arsenic metabolism on the occurrence of cancers among residents in arseniasis-endemic areas: A cohort subset with average fifteen-year follow-up.

Background: Chronic exposure to inorganic arsenic results in many cancers in susceptible persons. The metabolism of inorganic arsenic and genomic susceptibility are thought to be associated with cancer occurrence.

Methods: This study aims to examine the interaction of genomic susceptibility markers and urinary methylation capacity indicators involved in inorganic arsenic metabolism with all-cancer occurrence.

A Ras-LSD1 axis activates PI3K signaling through PIK3IP1 suppression.

PI3K Interacting Protein 1 (PIK3IP1) is a suppressor of the PI3K/Akt/mTOR pathway. We previously reported that activated Ras suppresses PIK3IP1 expression to positively regulate the PI3K pathway in cancer cells. Using doxycycline-inducible PIK3IP1, here we confirm that reversing the effect of Ras by inducing expression of PIK3IP1 suppresses Ras-induced anchorage-independent growth, supporting the central role of PIK3IP1 in transformation.

RATES AND RISK FACTORS FOR RECURRENCE OF RETINOPATHY OF PREMATURITY AFTER LASER OR INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR MONOTHERAPY.

Purpose: To determine the rates and risk factors of recurrent retinopathy of prematurity (ROP) treated by laser photocoagulation, intravitreal bevacizumab (IVB) monotherapy, or intravitreal ranibizumab (IVR) monotherapy.

Methods: In this retrospective cohort study, consecutive infants with Type 1 ROP who received laser, IVB, or IVR treatments were followed for at least 75 weeks of postmenstrual age. Data analysis was performed between March 2010 and February 2017 in Chang Gung Memorial Hospital, Linkou, Taiwan.

Factors associated with adverse drug reaction occurrence and prognosis, and their economic impacts in older inpatients in Taiwan: a nested case-control study.

Objective: Older patients are likely to have higher disease complexity and more drug prescriptions of which are associated with a higher incidence of adverse drug reactions (ADR). This study aimed to investigate factors associated with ADR occurrence, prognosis and medical expenses in older inpatients.

Design: A nested case-control study.

Lifestyle characteristics as moderators of the effectiveness of weight control interventions among semiconductor workers.

Background: Workers in high technology industry are experiencing stressful environment and have been ranked as a high risk group for adverse health effects. The effectiveness of worksite health promotion is important for occupational health. This study is to investigate the effect of health interventions on body measurement changes while examining the role of their lifestyle factors.

Prodrugs of the cancer cell selective anti-cancer agent (Z)-2-(1H-indol-3-yl)-3-(isoquinolin-5-yl)acrylonitrile (A131) are orally efficacious in a mouse model of resistant colon cancer.

A131 (1) possesses a unique cancer cell selective dual mechanism of action where cancer cells are killed but normal cells only undergo growth arrest and are able to regrow after removal of 1. SAR studies of 1 indicate that only the specific structure of 1 elicits the full pharmacological effect. However, application of 1 in mouse models of cancer has been hampered by its low solubility and stability when given orally.

Predicting Type 2 Diabetes Mellitus Occurrence Using Three-Dimensional Anthropometric Body Surface Scanning Measurements: A Prospective Cohort Study.

Background: An accurate and comprehensive anthropometric measure for predicting type 2 diabetes mellitus (T2DM) has not yet been depicted.

Methods: A total of 8450 nondiabetic participants were recruited during 2000-2010 in Taiwan. The cohort was followed up to the end of 2013, over an average of 8.

Discovery of the cancer cell selective dual acting anti-cancer agent (Z)-2-(1H-indol-3-yl)-3-(isoquinolin-5-yl)acrylonitrile (A131).

Selective targeting of cancer cells over normal cells is a key objective of targeted therapy. However few approaches achieve true mechanistic selectivity resulting in debilitating side effects and dose limitation. In this work we describe the discovery of A131 (4a), a new agent with an unprecedented dual mechanism of action targeting both mitosis and autophagy.

Chest width, waist circumference, and thigh circumference are predictors of dementia.

Objective: Few studies have investigated the relationship between specific body measures and dementia.

Methods: Three-dimensional anthropometric body surface scanning data containing 38 body measures were collected from 6831 participants from the health examination department of a medical center in Taiwan during 2000 to 2008, and 236 dementia cases were identified during the 10-year follow-up. A multiple Cox regression analysis was performed.

Dual blockade of the lipid kinase PIP4Ks and mitotic pathways leads to cancer-selective lethality.

Achieving robust cancer-specific lethality is the ultimate clinical goal. Here, we identify a compound with dual-inhibitory properties, named a131, that selectively kills cancer cells, while protecting normal cells. Through an unbiased CETSA screen, we identify the PIP4K lipid kinases as the target of a131.

Opposing Activities of Aurora B Kinase and B56-PP2A Phosphatase on MKlp2 Determine Abscission Timing.

After cleavage furrow ingression during cytokinesis, nascent daughter cells remain connected by an intercellular bridge (ICB) and the midbody [1, 2]. The midbody becomes an assembly platform for ESCRT complexes that split apart the plasma membrane (PM) anchored to the ICB and complete abscission, which is the final step of cell division [3-5]. Aurora B governs abscission by regulating its timing as a checkpoint [6-10].

Predictive factors for hospitalization of nonurgent patients in the emergency department.

Nonurgent emergency department (ED) patients are a controversial issue in the era of ED overcrowding. However, a substantial number of post-ED hospitalizations were found, which prompted for investigation and strategy management. The objective of this study is to identify risk factors for predicting the subsequent hospitalization of nonurgent emergency patients.

Long-Term and Interactive Effects of Pay-For-Performance Interventions among Diabetic Nephropathy Patients at the Early Chronic Kidney Disease Stage.

Chronic kidney disease (CKD) is a major health problem worldwide because of the aging population and lifestyle changes. One of the important etiologies of CKD is diabetes mellitus (DM). The long-term effects of pay-for-performance (P4P) on disease progression have not been thoroughly examined.

Neurodevelopmental Outcomes in Infants with Retinopathy of Prematurity and Bevacizumab Treatment.

Purpose: The current study aims to investigate the neurodevelopment of premature infants after intravitreal injections of bevacizumab (IVB) for the treatment of retinopathy of prematurity (ROP) up to the age of 2 years.

Methods: The study design was retrospective observational case series conducted at an institutional referral center. Infants with type 1 ROP were classified into 3 groups: laser only, IVB only, and a combination of IVB and laser treatment.

The Tumor Suppressor Cdkn3 Is Required for Maintaining the Proper Number of Centrosomes by Regulating the Centrosomal Stability of Mps1.

Supernumerary centrosomes promote the assembly of abnormal spindles in many human cancers. The observation that modest changes in the centrosomal levels of Mps1 kinase can cause centrosome overduplication in human cells suggests the existence of a regulatory system that may tightly control its centrosomal stability. Here, we show that Cdkn3, a Cdk-associated phosphatase, prevents Mps1-mediated centrosome overduplication.

The relationship between type 2 diabetic patients' early medical care-seeking consistency to the same clinician and health care system and their clinical outcomes.

The literature has demonstrated that the continuity of diabetes care can lower medical service utilization and expenses. However, few studies have examined the effects of patients' medical care-seeking behaviors in the early stage after the diagnosis of diabetes on their long-term prognoses. This study aimed to examine the association of medical care-seeking behavior in the first year following diabetes diagnosis on the occurrence of diabetes-related complications among patients in Taiwan.

Serum levels of vascular endothelial growth factor and related factors after intravitreous bevacizumab injection for retinopathy of prematurity.

Importance: Intravitreous injections of bevacizumab (IVB) have been found to be effective for the treatment of retinopathy of prematurity (ROP). However, serum levels of vascular endothelial growth factor (VEGF) have been found to be suppressed for 2 weeks after IVB in patients with ROP. Changes in serum VEGF levels after IVB in patients with ROP may be important because VEGF also plays a role in the neurodevelopment of newborns.

Lens subluxation after plasmin and SF6 injections in rabbit eyes.

Purpose: To investigate the rate of lens subluxation following plasmin and/or SF6 injections in eyes, and whether a subsequent elevated level of vascular endothelial growth factor (VEGF) and vitreous tap would aggravate subluxation.

Methods: Four groups of rabbits were used. Group 1 received an intravitreal injection (IVI) of plasmin and SF6 in the right eye; group 2 received an IVI of plasmin in the right eye; group 3 received an IVI of SF6 in the right eye; and group 4 received an IVI of balanced salt solution in the right eye.