The mutational landscape and functional effects of noncoding ultraconserved elements in human cancers.

The mutational landscape of phylogenetically ultraconserved elements (UCEs), especially those in noncoding DNAs (ncUCEs), and their functional relevance in cancers remain poorly characterized. Here, we perform a systematic analysis of whole-genome and in-house targeted UCE sequencing datasets from more than 3000 patients with cancer of 13,736 UCEs and demonstrate that ncUCE somatic alterations are common. Using a multiplexed CRISPR knockout screen in colorectal cancer cells, we show that the loss of several altered ncUCEs significantly affects cell proliferation.

Clonal dominance defines metastatic dissemination in pancreatic cancer.

Tumors represent ecosystems where subclones compete during tumor growth. While extensively investigated, a comprehensive picture of the interplay of clonal lineages during dissemination is still lacking. Using patient-derived pancreatic cancer cells, we created orthotopically implanted clonal replica tumors to trace clonal dynamics of unperturbed tumor expansion and dissemination.

Targeting DNA2 overcomes metabolic reprogramming in multiple myeloma.

DNA damage resistance is a major barrier to effective DNA-damaging therapy in multiple myeloma (MM). To discover mechanisms through which MM cells overcome DNA damage, we investigate how MM cells become resistant to antisense oligonucleotide (ASO) therapy targeting Interleukin enhancer binding factor 2 (ILF2), a DNA damage regulator that is overexpressed in 70% of MM patients whose disease has progressed after standard therapies have failed. Here, we show that MM cells undergo adaptive metabolic rewiring to restore energy balance and promote survival in response to DNA damage activation.

Ether phospholipids are required for mitochondrial reactive oxygen species homeostasis.

Mitochondria are hubs where bioenergetics, redox homeostasis, and anabolic metabolism pathways integrate through a tightly coordinated flux of metabolites. The contributions of mitochondrial metabolism to tumor growth and therapy resistance are evident, but drugs targeting mitochondrial metabolism have repeatedly failed in the clinic. Our study in pancreatic ductal adenocarcinoma (PDAC) finds that cellular and mitochondrial lipid composition influence cancer cell sensitivity to pharmacological inhibition of electron transport chain complex I.

Targeting DNA2 Overcomes Metabolic Reprogramming in Multiple Myeloma.

Unlabelled: DNA damage resistance is a major barrier to effective DNA-damaging therapy in multiple myeloma (MM). To discover novel mechanisms through which MM cells overcome DNA damage, we investigated how MM cells become resistant to antisense oligonucleotide (ASO) therapy targeting ILF2, a DNA damage regulator that is overexpressed in 70% of MM patients whose disease has progressed after standard therapies have failed. Here, we show that MM cells undergo an adaptive metabolic rewiring and rely on oxidative phosphorylation to restore energy balance and promote survival in response to DNA damage activation.

Cueing quality: Unpacking country-of-origin effects on intentions to vaccinate against COVID-19 in Taiwan.

While existing studies have reported and recognized country-of-origin effects on the intentions to vaccinate against COVID-19 among individual citizens in some countries, the causal mechanism behind such effects to inform public health policymakers remain unexplored. Adding up a quality cue explanation for such effects to the existing literature, the authors argue that individual consumers are less willing to get a vaccine designed and manufactured by a country with a significantly lower quality perception than other countries. A survey experiment that recruited a nationally representative sample of Taiwanese adults (n = 1951) between December 13, 2020 and January 11, 2021 was designed and conducted to test the argument.

Immune landscape of a genetically engineered murine model of glioma compared with human glioma.

Novel therapeutic strategies targeting glioblastoma (GBM) often fail in the clinic, partly because preclinical models in which hypotheses are being tested do not recapitulate human disease. To address this challenge, we took advantage of our previously developed spontaneous Qk/Trp53/Pten (QPP) triple-knockout model of human GBM, comparing the immune microenvironment of QPP mice with that of patient-derived tumors to determine whether this model provides opportunity for gaining insights into tumor physiopathology and preclinical evaluation of therapeutic agents. Immune profiling analyses and single-cell sequencing of implanted and spontaneous tumors from QPP mice and from patients with glioma revealed intratumoral immune components that were predominantly myeloid cells (e.

Estimating global burden of COVID-19 with disability-adjusted life years and value of statistical life metrics.

Background: Global burden of COVID-19 has not been well studied, disability-adjusted life years (DALYs) and value of statistical life (VSL) metrics were therefore proposed to quantify its impacts on health and economic loss globally.

Methods: The life expectancy, cases, and death numbers of COVID-19 until 30th April 2021 were retrieved from open data to derive the epidemiological profiles and DALYs (including years of life lost (YLL) and years loss due to disability (YLD)) by four periods. The VSL estimates were estimated by using hedonic wage method (HWM) and contingent valuation method (CVM).

Economic evaluation for mass vaccination against COVID-19.

Background: Vaccine is supposed to be the most effective means to prevent COVID-19 as it may not only save lives but also reduce productivity loss due to resuming pre-pandemic activities. Providing the results of economic evaluation for mass vaccination is of paramount importance for all stakeholders worldwide.

Methods: We developed a Markov decision tree for the economic evaluation of mass vaccination against COVID-19.

Medium-Chain Acyl-CoA Dehydrogenase Protects Mitochondria from Lipid Peroxidation in Glioblastoma.

Glioblastoma (GBM) is highly resistant to chemotherapies, immune-based therapies, and targeted inhibitors. To identify novel drug targets, we screened orthotopically implanted, patient-derived glioblastoma sphere-forming cells using an RNAi library to probe essential tumor cell metabolic programs. This identified high dependence on mitochondrial fatty acid metabolism.

Pooled library screening with multiplexed Cpf1 library.

Capitalizing on the inherent multiplexing capability of AsCpf1, we developed a multiplexed, high-throughput screening strategy that minimizes library size without sacrificing gene targeting efficiency. We demonstrated that AsCpf1 can be used for functional genomics screenings and that an AsCpf1-based multiplexed library performs similarly as compared to currently available monocistronic CRISPR/Cas9 libraries, with only one vector required for each gene. We construct the smallest whole-genome CRISPR knock-out library, Mini-human, for the human genome (n = 17,032 constructs targeting 16,977 protein-coding genes), which performs favorably compared to conventional Cas9 libraries.

Syndecan 1 is a critical mediator of macropinocytosis in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) remains recalcitrant to all forms of cancer treatment and carries a five-year survival rate of only 8%. Inhibition of oncogenic KRAS (hereafter KRAS*), the earliest lesion in disease development that is present in more than 90% of PDACs, and its signalling surrogates has yielded encouraging preclinical results with experimental agents. However, KRAS*-independent disease recurrence following genetic extinction of Kras* in mouse models anticipates the need for co-extinction strategies.

Gender inequality, economic growth, and the intergenerational transmission of adverse health consequences at birth.

We estimate a gender differential in the intergenerational transmission of adverse birth outcomes. We link Taiwan birth certificates from 1978 to 2006 to create a sample of children born in the period 1999-2006 that includes information about their parents and their maternal grandmothers. We use maternal-sibling fixed effects to control for unobserved family-linked factors that may be correlated with birth outcomes across generations, and define adverse birth outcomes as small for gestational age.

The Intergenerational Transmission of Low Birth Weight and Intrauterine Growth Restriction: A Large Cross-generational Cohort Study in Taiwan.

Objectives Our research provides evidence on the intergenerational fetal programming effect by examining associations in the low birth weight (LBW, birth weight <2500 g) and intrauterine growth restriction (IUGR) status between two adjacent generations from both the maternal and paternal sides. Methods Birth certificate data of the entire Taiwanese population are used to construct three-consecutive-generational samples. The final samples consist of the third-generation children born during 1999-2006 to at least one second-generation (G2) parent born during 1978-1985.

The Short-Run and Long-Run Effects of Birth Weight: Evidence from Large Samples of Siblings and Twins in Taiwan.

In this paper, we assemble five large administrative data sets in Taiwan to investigate the short-run and long-run effects of birth weight. Comparing with previous studies, our results are more precisely estimated due to the large sample size. Using administrative data sets, the problems arising from self-reported samples are also mitigated.

Parental age difference, educationally assortative mating and offspring count: evidence from a contemporary population in Taiwan.

Using contemporary population data from Taiwan, we examine the relationships between parental age difference, educationally assortative mating, income and offspring count. Controlling for women's reproductive value (measured by age at first birth), we find that an older husband is associated with fewer offspring, whereas a husband with similar or higher education is associated with more offspring. Concerning resources, we find that women's income is negatively associated with fertility and husband's income is positively associated with fertility among highly educated women.

Valuation of the economic benefits of human papillomavirus vaccine in Taiwan.

Objectives: The study aims to apply the contingent valuation method to elicit the willingness-to-pay (WTP), and measure the value of a statistic life (VSL), for human papillomavirus (HPV) vaccine in Taiwan.

Methods: A total of 512 questionnaires were completed on women aged 20 to 55 years with at least one daughter, during March through May 2007. The respondents' WTP for the vaccines was elicited by double-bounded binary-choice questions under two scenarios: one was to protect themselves from cervical cancer (CC) and the other was for their daughter(s).

Parental Education and Child Health: Evidence from a Natural Experiment in Taiwan.

In 1968, the Taiwanese government extended compulsory education from six to nine years and opened over 150 new junior high schools at a differential rate among regions. Within each region, we exploit variations across cohorts in new junior high school openings to construct an instrument for schooling and employ it to estimate the causal effects of mother's or father's schooling on infant birth outcomes in the years 1978-1999. Parents' schooling does indeed cause favorable infant health outcomes.

Do lower birth weight babies have lower grades? Twin fixed effect and instrumental variable method evidence from Taiwan.

By combining two unique Taiwanese datasets, this paper investigates how birth weight affects grades at age 15 years. To tackle the endogeneity problem caused by omitted variables, we first compare birth weight and grade variation within twins. We find that birth weight does increase grades but only when both twins weigh less than 3000g at birth, which indicates that the effect is non-linear, and when the weight difference between the twins is larger than 200g.

Willingness to pay for weight-control treatment.

Objectives: To estimate willingness to pay (WTP) for alternative forms of weight-control treatment and evaluate how it varies with individual characteristics.

Methods: Contingent valuation (CV) survey of employed females in Taiwan using double-bounded dichotomous-choice question format and telephone interview. Statistical models include an estimated correction for sample-selection bias associated with respondents' interest in weight loss.

Academic achievement of twins and singletons in early adulthood: Taiwanese cohort study.

Objectives: To examine the long term effects of low birth weight on academic achievements in twins and singletons and to determine whether the academic achievement of twins in early adulthood is inferior to that of singletons.

Design: Cohort study.

Setting: Taiwanese nationwide register of academic outcome.

Hospital ownership and performance: evidence from stroke and cardiac treatment in Taiwan.

This paper compares program expenditure and treatment quality of stroke and cardiac patients between 1997 and 2000 across hospitals of various ownership types in Taiwan. Because Taiwan implemented national health insurance in 1995, the analysis is immune from problems arising from the complex setting of the U.S.

As low birth weight babies grow, can well-educated parents buffer this adverse factor? A research note.

This research note combines two national Taiwanese data sets to investigate the relationships among low birth weight (LBW) babies, their parents' educational levels, and their future academic outcomes. We find that LBW is negatively correlated with the probability of such children attending college at age 18; however, when both parents are college or high school graduates, such negative effects may be partially offset. We also show that discrimination against daughters occurs, but only for daughters who were LBW babies.

Willingness to pay for drug abuse treatment: results from a contingent valuation study in Taiwan.

Objective: In this study, we attempted to describe and justify the use of a contingent valuation (CV) method to elicit the willingness to pay (WTP) for a drug abuse treatment program by the general public in Taiwan.

Method: In total, 1817 CV survey questionnaires were conducted through telephone interviews from randomly dialed numbers. Subjects were members of the general public aged between 20 and 65 years, with full-time jobs, and residing in the three major Taiwanese cities of Taipei, Taichung, and Kaohsiung.

Delayed parenthood and the risk of cesarean delivery--is paternal age an independent risk factor?

Background: Between 1995 and 2001, the average cesarean section rates in Taiwan were as high as 33.34 percent. This study set out to determine the independent effects of paternal age on the likelihood of cesarean delivery among a sample of Taiwanese women.