bluuebunny/crossref_metadata_2025 huggingface dataset:
Inclusive Growth toward a Harmonious Society in the People’s Republic of China: Policy Implications
Authors: Zhuang Juzhong
Published: June 2023

This paper examines the policy implications of adopting a development strategy anchored on inclusive growth for the People’s Republic of China (PRC). In response to rising inequality, more and more developing Asian countries are embracing inclusive growth, with its focus on creating economic opportunities and ensuring equal access to them, as the goal of development policy. Inclusive growth provides an effective means to create a harmonious society in the PRC. The paper argues that an inclusive growth strategy for the PRC requires continued reforms to keep growth high and sustainable, carefully designed redistributive policy to promote equal access to opportunities, and good governance and strong institutions to ensure economic and social justice and an even playing field.
New Multinationals from Emerging Asia: The Case of National Oil Companies
Authors: Goldstein Andrea
Published: June 2023

The history of global foreign direct investment (FDI ) and of the rise of multinational enterprises is, to a large extent, the history of the global oil industry. In the twentieth century, oil-producing Asia was one of the main destinations of global oil FDI flows and in the early twenty-first century Asia, including both producer and consumer countries, is home to some of the most dynamic oil companies worldwide. This paper first examines the oil industry in Emerging Asia to identify the main actors in terms of production, ownership, and governance. The main features of the multinational expansion of the largest Asian national oil companies, in terms of country of operation, patterns of integration, and entry mode, are discussed. The concluding section outlines some of the main implications of this international drive, comparing it with the rise of the Italian energy company Eni in the 1950s.
Workers’ Earnings in the Philippines: Comparing Self-Employment with Wage Employment
Authors: Hasan Rana , Jandoc Karl Robert L.
Published: June 2023

Analysis of labor force survey (LFS) data since the early 1990s reveals several important changes in the structure of the Philippine labor force. One is the movement from self-employment to wage employment across a wide range of production sectors. To evaluate this change in terms of workers’ earnings, we combine information on household incomes from the Family Income and Expenditure Survey with information on household members’ employment-related activities from the LFS. We also examine broad structural trends for employment, wages, and earnings. The findings indicate high variance in the earnings of the self-employed and their earnings and educational profiles resemble those of casual wage employees. Both are surpassed by those of permanent wage employees even when observable worker characteristics are controlled for. As self-employment gives way to wage employment, especially casual wage employment in the services sector, the key policy challenge is tackling the slow growth of wages and earnings.
Regional Economic Impacts of Large Projects: A General Equilibrium Application to Cross-Border Infrastructure
Authors: Warr Peter , Menon Jayant , Yusuf Arief Anshory
Published: June 2023

A general equilibrium framework is used to study the regional economic effects of infrastructure improvements designed to reduce the costs of interregional trade. The results suggest that in the short run the kind of transport cost reductions consistent with improvement of inter-regional transport facilities will produce a modest increase in inter-regional trade volumes in both directions. This coincides with a small increase in real consumption in both regions and correspondingly small reductions in poverty incidence. Over a longer period, the benefits to both regions, including reductions in poverty incidence, are much larger, as investors respond to the changed structure of incentives with new capital investments, and as workers move to regions of greater return to their labor. Because these benefits are significant in both regions, the results do not confirm the common presumption that the benefits from cross-border infrastructure projects occur only, or overwhelmingly, in the richer region.
Collective Action, Political Parties, and Pro-Development Public Policy
Authors: Keefer Philip
Published: June 2023

Broad consensus exists that the ability of political actors to make credible commitments is key to development. An important and little-explored determinant of the credibility of political commitments is the existence of organizations that facilitate citizen collective action to sanction political actors who renege. This paper focuses on one essential organization, the political party. Three measures of political parties are used to assess cross-country differences in the degree to which politicians facilitate the ability of citizens to act in their collective interest. Each of these measures is associated with superior development outcomes, above and beyond the effects of competitive elections. These results have implications for understanding the extraordinary economic success of some East Asian countries and notable lags among others. East Asian nondemocracies exhibit more institutionalized ruling parties than other nondemocracies, while East Asian democracies exhibit equally or less institutionalized parties. The evidence suggests that greater research and policy emphasis be placed on the organizational characteristics of countries that allow citizens to hold leaders accountable.
Infrastructure and Growth in Developing Asia
Authors: Straub Stéphane , Terada-Hagiwara Akiko
Published: June 2023

This paper applies two distinct approaches—growth regressions and growth accounting—to analyze the link between infrastructure, growth, and productivity in developing Asian countries. The main conclusion is that a number of countries in developing Asia have significantly improved their basic infrastructure endowments in the recent past. This improvement appears to correlate significantly with good growth performances. However, the evidence seems to indicate that this is mostly the result of factor accumulation, a direct effect, and that the impact on productivity is rather inconclusive.
Forecasting Volatility in Asian Stock Markets: Contributions of Local, Regional, and Global Factors
Authors: Wang Jianxin
Published: June 2023

This paper examines volatility forecasting for the broad market indices of 12 Asian stock markets. After considering the long memory in volatility and volatility jumps, the paper incorporates local, regional, and global factors into a heterogeneous autoregressive model for volatility forecasting. Compared to several existing studies, the model produces smaller forecasting errors. The empirical findings shed new light on the spillover effect from regional and global factors to local market volatility. Despite the common perception of increased globalization, the paper finds that volatility in Asia is primarily driven by local factors. During the period January 2005 to April 2010, regional and global factors explain 2%–3% of the volatility in the next 10 days for Asian emerging markets, and 3%–6% for Asian developed markets. There was no significant increase in the contribution of global factors to local market volatility.
Does East Asian Integration Keep Up with the European Pattern? Empirical Evidence from Intra-Industry Trade in Europe and East Asia
Authors: Kang Yoo-Duk
Published: June 2023

This paper examines development of inter/intra-industry trade in Europe and East Asia. In order to quantify the level of intra-industry trade (IIT), a biascorrected Grubel and Lloyd index is used. The finding is that IIT is more evident in intra-European trade than in intra-East Asian trade, while dynamics toward IIT have been increasingly more important in trade between East Asian economies. Vertical intra-industry trade and horizontal intra-industry trade are compared, and their share in intraregional trade in both regions is measured. The paper finds that IIT in East Asia is characterized by vertical intra-industry trade. In order to identify determinants of IIT in Europe and East Asia, a regression analysis is used, which finds that conventional determinants of IIT explain a large part of IIT in Europe, while they do not for East Asian countries. In East Asia, IIT takes place between developed countries in the region.
Economics and the Family
Authors: Sen Amartya
Published: June 2023

The family is a remarkable institution. And a complex one. Indeed, so complex that much of economic theory proceeds as if no such thing exists. In the standard theory of prices and equilibrium (the most elegant version of which is to be found in the theory of general equilibrium), individuals and firms are visible, but definitely no families. The individual owns resources, sells them, earns an income, buys goods and services, and has utilities. The firm buys resources, makes commodities, sells them, makes profits, and gives incomes to individual owners. So the story runs, with no family in sight – and children neither heard nor seen.
External Shocks and Policy Responses: The Asian Experience
Authors: Naya Seiji , Kim D.H. , James W.
Published: June 2023

This article examines the impact of oil price increases and world recessions in the 1970s on the balance of payments of 12 developing countries in Asia. The analysis is in the long term. It views the current debt problems in the context of the turbulent world economy of the 1970s and of economic management within the countries. In doing so, it assesses the effectiveness of various policy responses of the Asian countries to challenges posed by the external shocks…
Human Resource Development in Asia: Achievements and Tasks Ahead
Authors: Luthra K. L.
Published: June 2023

Improving the health and level of education of a country’s population is both a means and an end of economic development. The importance of human resource development as a means of promoting economic growth is now well acknowledged, and developing countries have been allocating large amounts of resources to education and health programs. This has led to improvements: literacy rates are going up with the extended provision of schooling, crude death rates are declining as a result of better health services, and life expectancy is improving…
Organizational Dualism and Economic Development
Authors: Myint H.
Published: June 2023

Dualism may be characterized by the coexistence of a “modern” sector and a “traditional” sector within the framework of the same economic system. While remnants of dualism may survive even in the most advanced industrial economies, it is pre-eminently a phenomenon of underdeveloped economies…
Agricultural Strategies and Agrarian Structure
Authors: Johnston Bruce F. , Tomich Thomas P.
Published: June 2023

To declare that “small is beautiful” is a rhetorical indulgence. To emphasize that, for the great majority of farm units in developing countries, “small is inevitable” is to recognize a fact that derives from a country’s structural and demographic characteristics. Because farm populations continue to grow while the scope for expanding area under cultivation increasingly is limited, the trend will be toward smaller farm units in many low-income developing countries…
Asian Development: A View from the Paddy Fields
Authors: Hayami Yujiro
Published: June 2023

It may be presumptuous for a pedestrian agricultural economist such as myself to present an overall perspective of Asian economic development. I know little about sophisticated macroeconomic models, and even less about the preferences and decision-making rules of politicians, bureaucrats and business executives. I am, however, familiar with work and life in rural villages in the rice-producing regions of Asia, and thus present my view in the hope that it will provide a perspective which is somewhat different from that of development theorists and planners.
Malaysia: In Pursuit of Newly Industrializing Economy Status
Authors: Onn Fong Chan
Published: June 2023

Malaysia has an ambitious economic vision: it has set its sights on joining the ranks of the newly industrializing economies (NIEs). It hopes to achieve this goal within the next decade, by building up an advanced export-oriented manufacturing structure alongside a vibrant agriculture sector. While the modernization and diversification of agriculture would be achieved through the acceleration of new land development schemes as well as the cultivation of new crops, apart from existing rubber and oil palm, the speeding up of industrialization would be attained through a multipronged coordinated strategy…
Policies for Poverty Alleviation
Authors: Ahluwalia Montek S.
Published: June 2023

The phenomenon of mass poverty in developing countries and its relationship to the development process has been the subject of intense study for the past two decades. As a result, a considerable consensus has emerged on a number of issues. The pessimistic view that the growth process in developing countries has the perverse effect of actually accentuating poverty commands far fewer followers today than it once did. It is now widely recognized that the process of growth in most countries, even if not as equitable as might be wished, has at least led to significant improvements in the conditions of living of the poor. However, it is also evident that in many countries the pace of improvement has been slow, and in general much below expectations…
Monetary Policy in Asian Economic Development
Authors: Leeahtam Pisit , Patrawimolpon Pichit , Supapongse Mathee
Published: June 2023

The purpose of this article is to: (i) examine the conduct of monetary policy in selected Asian economies; (ii) trace the economic development and structural changes which interact with the effectiveness of monetary policy; and (iii) seek an appropriate development path for monetary authorities in facilitating sustained economic growth with stability under rapidly changing world and regional economic conditions…
Rural Poverty in Thailand: Policy Issues and Responses
Authors: Krongkaew Medhi , Tinakorn Pranee , Suphachalasai Suphat
Published: June 2023

One of the most nagging problems in the economic management of a country is achieving high rate of economic growth while reducing absolute and relative poverty. Nowhere in Southeast Asia, or even in Asia, has the problem of growth-equity trade-off become more unique and interesting than in Thailand. Toward the end of the 1980s, Thailand was one of the few countries in Asia which had achieved a gross domestic product (GDP) growth rate of over 10 per cent a year. And yet, it is also well known that income distribution in Thailand has worsened, and the absolute level of poverty has not declined in the last ten years…
The Role of Foreign Investment in the Economic Growth of the Asian and Pacific Region
Authors: Ruffin Roy J.
Published: June 2023

Among both developing and developed countries, Asian countries are the “superstars” of economic growth. Using the best available measures, one study found that “Asian” countries (including Japan and the Middle East) produced 25 per cent of world output in 1960 and a remarkable 36 per cent of world output in 1988. Thus, this group of countries now produces a larger fraction of world output than any other group, such as North America or Europe. But what is more remarkable is that the developing countries in Asia and the Pacific produced 25 per cent of world output in 1988—the same as the United States. Updating these statistics to 1991 would result in a U.S. share of about 23 per cent while developing Asia’s share would be about 27 per cent…
Foreign Direct Investment in East Asia
Authors: Chen Edward K.Y.
Published: June 2023

Foreign direct investment (FDI) has played an important role in the economic development of the Asia-Pacific region. In the past, FDI was mainly from the Western industrialized countries such as the United States and Britain. Since the late 1980s, however, intraregional direct investment has been growing very rapidly, signifying an increasing economic integration and cooperation within the region. Japan, one of the economic superpowers, has become a major source of investment in the region. Moreover, the Asian newly industrializing economies (NIEs)—Hong Kong; Republic of Korea; Singapore; and Taipei, China—which have experienced remarkable economic growth, also invest substantially in other Asian developing countries…
Intraregional Trade in the Asian and Pacific Region
Authors: Lloyd P.J.
Published: June 2023

This paper examines trends in intraregional trade of the Asian and Pacific countries in the context of global trends. Trade in the Asian region has grown more rapidly than trade in any other region of the world economy. A constant-market-share analysis reveals that this is partly due to the concentration of Asian exports on manufactures, which are the fastest growing component of goods trade, but primarily due to the increase in the market share for goods exported from Asian countries. The growth in intra-Asian trade is primarily explicable in terms of the rapid rate of total trade of the East Asian region rather than being a structural change. Intra-Asian trade has also been increased by the unilateral reduction in trade barriers by many Asian countries and the rapid expansion of intra-Asian direct foreign investment. Despite the expansion in intraregional trade, East Asia is much less integrated than the European Union or North America in terms of the convergence of factor and goods prices and the degree of uniformity of policy.
India — Reform on Hold
Authors: Joshi Vijay , Little I. M. D.
Published: June 2023

In 1991, India embarked on economic reforms that have the potential to transform its future economic development. This paper is an evaluation of these reforms. It analyzes the progress made in the last seven years, considers the likelihood of its continuance, and suggests an agenda for the future. The authors conclude that while there has been significant movement in some areas, the reforms, as a whole, have been slow and unbalanced and are as yet highly incomplete. They are fairly pessimistic about the political feasibility of the reforms and sceptical about greater devolution of powers and responsibilities to the States as the way forward.
Educational Development in Asia: Issues in Planning, Policy, and Finance
Authors: Lewin Keith M.
Published: June 2023

Most Asian countries have consistently invested heavily in education over the last three decades. Access, participation, and achievement have reached unprecedented levels throughout the region, albeit large differences remain between the more developed and less developed systems. It is widely believed that economic growth in the 21st century will depend on the deployment of the intellectual capital that is developed by effective education systems. The educational challenge this presents is to find ways to continue raising the levels of educational endowments at sustainable levels of cost, especially where austerity creates short-term constraints on public finance. This paper locates recent educational development in an international context and profiles the current status of educational investment in different groups of Asian countries. It explores the issues that are likely to shape how systems will evolve in the first part of the 21st century, and provides analyses of the impact of demographic trends, and of the factors that will influence public financing, patterns of resource allocation, and internal efficiency. The results of these analyses are translated into future scenarios for different groups of countries. The paper concludes with a series of policy-oriented conclusions that identify priorities for governments and donors.
Ecology, Inequality, and Poverty: The Case of Bangladesh
Authors: Khan Haider Ali
Published: June 2023

This paper explores the connections between environmental damages, inequality, and poverty for Bangladesh. Starting with a new concept of national income and its distribution, which takes ecological damages into account, standard measures of poverty and inequality are modified by using the adjusted income distribution for their measurement. Under fairly conservative assumptions of modest environmental damages and a uniform distribution of the damages among the population, it is shown that both inequality and poverty worsen when environmental deterioration is taken into account. From a policy perspective, since there is no inevitable environmental Kuznets curve, developing countries like Bangladesh can enhance the poverty alleviation effects of growth by improving environmental quality through effective interventions.
Health and Nutrition in Emerging Asia
Authors: Osmani S. R. , Bhargava A.
Published: June 2023

This paper examines the quality of health and nutrition in emerging Asia. The objective is to assess the likely prospects for the early 21st century and identify the policy responses that may become necessary to meet new challenges or to deal with the persistent ones. The paper begins by assessing past achievements and failures in the areas of health and nutrition in Asia in comparison with the rest of the world, and then analyzes the differentials that exist within Asia—differentials between sexes, between urban and rural location, and between countries. Some simple models are then developed to explain intercountry differences in health outcomes. Among the persistent problems, the paper highlights the excessive incidence of malnutrition in South Asia. Among the emerging problems, special attention is given to the general problem of “overlapping health transition” and the specific problems of smoking-related diseases and a potential AIDS epidemic. The paper concludes by drawing out a number of policy implications.
Controlling Micronutrient Deficiencies in Asia
Authors: Mason John , Mannar Venkatesh , Mock Nancy
Published: June 2023

Vitamin A deficiency (VAD), iodine deficiency disorders (IDDs), and iron deficiency anemia (IDA) affect large numbers of the populations in Asia, often overlapping. Clinical VAD is probably declining, but subclinical VAD is common and carries significant mortality risk. IDDs fall when there are effective iodized salt programs. IDA persists unchanged at high levels, particularly affecting women and children. Deficiency control programs—notably high-dose vitamin A capsules six-monthly for children and iodized salt—are under way in many areas, and need to be sustained and made universal. Fortification is a key long-run solution, and multiple fortification and supplementation need to be researched and implemented. Better information is needed on programs and their impact; even baseline data are scarce. Public-private coalitions should be fostered with the food industry and others concerned. Capacity-building for the range of actions for controlling deficiencies should be an early next priority.
A metric for gravitational collapse around a Schwarzschild black hole
Authors: Erdem Recai , Demirkaya Betül , Gültekin Kemal
Published: June 2023

We consider the problem of gravitational collapse of a fluid under the effect of a small Schwarzschild black hole (e.g. a primordial one). We assume the fluid initially may be approximated by a uniform homogeneous dust. Starting from this configuration we obtain a class of metrics under some physically justified assumptions. We find that the metric we obtain includes the dust collapse as a subcase. After discussing some basic properties of the solution, we discuss the case of dust collapse in more detail. We find that the radial and tangential pressures outside the horizon may take positive or negative values depending on the values of the parameters.
Make It Real: An End-to-End Implementation of A Physically Disaggregated Data Center
Authors: Zhang Yiying
Published: June 2023

Resource disaggregation is an approach to separate different hardware resources into independent pools in a data center, so that these pools can be easily managed and their resources can be allocated in a tight but unbounded way. The past decade has seen research and practices in realizing the resource-disaggregation idea on regular servers.

We advocate for a physically disaggregated data center, where disaggregated resource pools consist of hardware devices, not servers. Physical disaggregation could unlock another level of benefits in resource disaggregation, including further improved cost saving, easier maintenance and scaling, and more customization. This paper presents our efforts in building an end-to-end physically disaggregated data center, including the design and implementation of disaggregated hardware devices, networking systems for connecting these devices, operating systems for orchestrating them, and porting of traditional and cloud-computing applications to this physically disaggregated platform.
Effect of PTGES3 on the Prognosis and Immune Regulation in Lung Adenocarcinoma
Authors: Jiang Wenyan , Wei Qiong , Xie Haiqin , Wu Dandan , He Haiyan , Lv Xuedong
Published: June 2023

Background. PTGES3 is upregulated in multiple cancer types and promotes tumorigenesis and progression. However, the clinical outcome and immune regulation of PTGES3 in lung adenocarcinoma (LUAD) are not fully understood. This study aimed to explore the expression level and prognostic value of PTGES3 and its correlation with potential immunotherapy in LUAD. Methods. All data were obtained from several databases, including the Cancer Genome Atlas database. Firstly, gene and protein expression of PTGES3 were analyzed using Tumor Immune Estimation Resource (TIMER), R software, Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA). Thereafter, survival analysis was conducted using the R software, Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and Kaplan–Meier Plotter. In addition, gene alteration and mutation analyses were conducted using the cBio Cancer Genomics Portal (cBioPortal) and Catalog of Somatic Mutations in Cancer (COSMIC) databases. The molecular mechanisms associated with PTGES3 were assessed via Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), GeneMANIA, GEPIA2, and R software. Lastly, the role of PTGES3 in immune regulation in LUAD was investigated using TIMER, Tumor‐Immune System Interaction Database (TISIDB), and SangerBox. Results. The gene and protein expression of PTGES3 were elevated in LUAD tissues and compared to the normal tissues, and the high expression of PTGES3 was correlated with cancer stage and tumor grade. Survival analysis revealed that overexpression of PTGES3 was associated with poor prognosis of LUAD patients. Moreover, gene alteration and mutation analysis revealed the occurrence of several types of PTGES3 gene alterations in LUAD. Moreover, co‐expression analysis and cross‐analysis revealed that three genes, including CACYBP, HNRNPC, and TCP1, were correlated and interacted with PTGES3. Functional analysis of these genes revealed that PTGES3 was primarily enriched in oocyte meiosis, progesterone‐mediated oocyte maturation, and arachidonic acid metabolism pathways. Furthermore, we found that PTGES3 participated in a complex immune regulation network in LUAD. Conclusion. The current study indicated the crucial role of PTGES3 in LUAD prognosis and immune regulation. Altogether, our results suggested that PTGES3 could serve as a promising therapeutic and prognosis biomarker for the LUAD.
Research on Liquid Flow Rate Detection of Mixed Fluid Based on Vibration Signal Characteristic Analysis of Gas Liquid Two-Phase Flow
Authors: Jian Zhang , Raja S. Selvakumar , Lei Liang , Shu Dai
Published: June 2023

The online detection of liquid flow rate in gas-liquid two-phase flow has become an important factor in ensuring the safe operation of gas wells. In this paper, the real-time measurement of liquid holdup in gas-liquid two-phase flow is carried out by analyzing the characteristics of vibration signals excited by gas-liquid two-phase flow impacting on the pipe wall. Firstly, an acceleration sensing detection and processing system is constructed to obtain the vibration signals excited by gas-liquid two-phase flow impacting on the pipe wall. Then, the pure airflow vibration signals at different flow velocities and the gas-liquid two-phase flow excitation vibration signals at different liquid flow rates are tested, respectively, and the time-frequency characteristics analysis based on STFT is implemented. The practice shows the following: firstly, the frequency band of 6.5−15 Hz is identified as the characteristic frequency band of liquid flow rate in gas-liquid two-phase flow. Secondly, the liquid holdup is positively correlated with the vibration energy in its characteristic frequency band. Thirdly, a mathematical model of the relationship between liquid flow rate and vibration energy is constructed. Finally, the measurement error of liquid holdup is within 10%. This research method has laid a good foundation for the subsequent detection of characteristic parameters of each phase in gas-solid-liquid complex multiphase flow fluids, and it has certain application and promotion value.
Cottonseed Meal Protein Hydrolysate Improves the Growth Performance of Chinese Mitten Crab (Eriocheir sinensis) by Promoting the Muscle Growth and Molting Performance
Authors: He Chao-Fan , Liu Wen-Bin , Zhang Ling , Chen Wei-Liang , Liu Zi-Shang , Li Xiang-Fei
Published: June 2023

Growth retardation and prolonged marketing cycle have been noticed in the practical aquaculture of Chinese mitten crab (Eriocheir sinensis) fed with artificial feed. Plant protein hydrolysates contain a large number of small peptides and free amino acids, which can improve the growth performance of aquatic animals. However, the potential mechanisms are still not well elucidated. In this research, the influences of cottonseed meal protein hydrolysate (CPH) on the growth, feed utilization, muscle growth, and molting performance were investigated in E. sinensis. A total of 240 crabs (mean body weight 37.32 ± 0.38 g) were individually randomly distributed to six diets supplemented with 0%, 0.2%, 0.4%, 0.8%, 1.6%, and 3.2% of CPH for 12 weeks. These findings indicated that the addition of CPH at 0.4% significantly increased the survival rate, body protein gain, apparent protein utilization, trypsin and pepsin activities, and the methyl farnesoate content. When the dose reached 0.8%, the weight growth ratio, meat yield, ecdysone concentration, and the transcription of the ecdysteroid receptor all significantly increased, while the transcriptions of both myostatin and molt-inhibiting hormone significantly decreased. When CPH was added at 1.6%–3.2%, the feed conversion ratio, body crude protein content, Na+/K+-ATPase activity, and the molting ratio were all significantly improved, while the opposite was true for the transcription of the transforming growth factor-β type I receptor. The investigation results indicated that when added above 0.4%, CPH could stimulate the growth performance of E. sinensis and promote the muscle growth and molting performance.
Supplementary Figure S5 from A Bifunctional PARP-HDAC Inhibitor with Activity in Ewing Sarcoma
Authors: Ramos Louise , Truong Sarah , Zhai Beibei , Joshi Jay , Ghaidi Fariba , Lizardo Michael M. , Shyp Taras , Kung Sonia H.Y. , Rezakhanlou Alireza M. , Oo Htoo Zarni , Adomat Hans , Le Bihan Stephane , Collins Colin , Bacha Jeffrey , Brown Dennis , Langlands John , Shen Wang , Lallous Nada , Sorensen Poul H. , Daugaard Mads
Published: June 2023

Replicate graphs of spheroid assays and cell fluorescence data
Supplementary Table S1 from Association of Antifolate Response Signature Status and Clinical Activity of Pemetrexed-Platinum Chemotherapy in Non–Small Cell Lung Cancer: The Piedmont Study
Authors: Eisner Joel R. , Mayhew Gregory M. , Davison James M. , Beebe Kirk D. , Shibata Yoichiro , Guo Yuelong , Farhangfar Carol , Farhangfar Farhang , Uronis Joshua M. , Conroy Jeffrey M. , Milburn Michael V. , Hayes David Neil , Mileham Kathryn F.
Published: June 2023

48 genes included in the new LUAD nearest centroid classifier and associated AF-PRS signature.
Data from Driving Diversity and Inclusion in Cancer Drug Development – Industry and Regulatory Perspectives, Current Practices, Opportunities, and Challenges
Authors: Fashoyin-Aje Lola A. , Tendler Craig , Lavery Bea , Ghiorghiu Serban , Gerald Brittany , Kalidas Chitkala , Richie Nicole , Winson Kathleen , Warren Nicholas J.H. , Tellman Tristen V. , Retzlaff Jon , Foti Margaret , Pazdur Richard
Published: June 2023

Abstract
In April 2022, the FDA issued draft guidance to help industry develop strategies to improve diversity in clinical trials. Historically, clinical trial sponsors have not systematically incorporated efforts to promote diversity, equity, and inclusion (DEI), particularly during the early design stages of clinical development plans and operational strategies. Unfortunately, a retrospective approach to DEI often results in clinical trial participants not being reflective of the diversity of patients intended to be treated with new therapies. A shift to prospective, intentional DEI strategies for clinical trials, including long-term engagement with diverse patients and communities throughout the development life cycle, is necessary to maximize the benefits and minimize the risks of new drugs and devices for all patients. Sponsors’ current practices and opportunities for improving DEI address four major topics: institutional commitment, culture change, and governance; clinical development strategy; setting enrollment goals to ensure trial participant diversity; and development and implementation of the operational strategy. As DEI practices gain wider adoption in clinical trials, shared learning and collaboration among stakeholders on an ongoing and noncompetitive basis will lead to sustainable change. Prioritization of enrollment of diverse populations as an integral part of study start-up planning, clinical trial design, and recruitment capabilities will enhance the clinical development process for oncology therapies. Importantly, these efforts will help provide equitable access to clinical trials and innovative cancer therapies.
Data from Association of Antifolate Response Signature Status and Clinical Activity of Pemetrexed-Platinum Chemotherapy in Non-Small Cell Lung Cancer - The Piedmont Study
Authors: Eisner Joel R. , Mayhew Gregory M. , Davison James M. , Beebe Kirk D. , Shibata Yoichiro , Guo Yuelong , Farhangfar Carol , Farhangfar Farhang , Uronis Joshua M. , Conroy Jeffrey M. , Milburn Michael V. , Hayes David Neil. , Mileham Kathryn F.
Published: June 2023

Abstract
Purpose: The Piedmont study is a prospectively designed retrospective evaluation of a new 48-gene antifolate response signature (AF-PRS) in patients with locally advanced/metastatic NS-NSCLC treated with pemetrexed-containing platinum doublet chemotherapy (PMX-PDC). The study tested the hypothesis that AF-PRS selects for patients with NS-NSCLC that preferentially respond to PMX-PDC, with a goal of providing clinical support for AF-PRS as potential diagnostic test. Experimental Design: Residual pre-treatment FFPE tumor samples and clinical data were analyzed from 105 patients treated with 1st-line (1L) PMX-PDC. 95 patients had sufficient RNA sequencing (RNAseq) data quality and clinical annotation for inclusion in the analysis. Associations between AF-PRS status and associate genes, and outcome measures including progression-free survival (PFS) and clinical response were evaluated. Results: Overall, 53% of patients were AF-PRS(+), which was associated with extended PFS, but not OS, vs. AF-PRS(-) (16.6 vs. 6.6 mo; p = 0.025). In patients who were Stage I-III patients at time of treatment, PFS was further extended in AF-PRS(+) vs. AF-PRS(-) (36.2 vs. 9.3 mo; p = 0.03). Complete response (CR) to therapy was noted in 14 of 95 patients. AF-PRS(+) preferentially selected a majority (79%) of CRs, which were evenly split between patients Stage I-III (6 of 7) and Stage IV (5 of 7) at time of treatment. Conclusions: AF-PRS identified a significant population of patients with extended PFS and/or clinical response following PMX-PDC treatment. AF-PRS may be a useful diagnostic test for patients indicated for systemic chemotherapy, especially when determining the optimal PDC regimen for locally advanced disease.
Resistance to Selective FGFR Inhibitors in FGFR-Driven Urothelial Cancer
Authors: Facchinetti Francesco , Hollebecque Antoine , Braye Floriane , Vasseur Damien , Pradat Yoann , Bahleda Rastislav , Pobel Cédric , Bigot Ludovic , Déas Olivier , Florez Arango Juan David , Guaitoli Giorgia , Mizuta Hayato , Combarel David , Tselikas Lambros , Michiels Stefan , Nikolaev Sergey I. , Scoazec Jean-Yves , Ponce-Aix Santiago , Besse Benjamin , Olaussen Ken A. , Loriot Yohann , Friboulet Luc
Published: June 2023

Several fibroblast growth factor receptor (FGFR) inhibitors are approved or in clinical development for the treatment of FGFR-driven urothelial cancer, and molecular mechanisms of resistance leading to patient relapses have not been fully explored. We identified 21 patients with FGFR-driven urothelial cancer treated with selective FGFR inhibitors and analyzed postprogression tissue and/or circulating tumor DNA (ctDNA). We detected single mutations in the FGFR tyrosine kinase domain in seven (33%) patients (FGFR3 N540K, V553L/M, V555L/M, E587Q; FGFR2 L551F) and multiple mutations in one (5%) case (FGFR3 N540K, V555L, and L608V). Using Ba/F3 cells, we defined their spectrum of resistance/sensitivity to multiple selective FGFR inhibitors. Eleven (52%) patients harbored alterations in the PI3K–mTOR pathway (n = 4 TSC1/2, n = 4 PIK3CA, n = 1 TSC1 and PIK3CA, n = 1 NF2, n = 1 PTEN). In patient-derived models, erdafitinib was synergistic with pictilisib in the presence of PIK3CA E545K, whereas erdafitinib–gefitinib combination was able to overcome bypass resistance mediated by EGFR activation.

Significance:

In the largest study on the topic thus far, we detected a high frequency of FGFR kinase domain mutations responsible for resistance to FGFR inhibitors in urothelial cancer. Off-target resistance mechanisms involved primarily the PI3K–mTOR pathway. Our findings provide preclinical evidence sustaining combinatorial treatment strategies to overcome bypass resistance.

See related commentary by Tripathi et al., p. 1964.

This article is featured in Selected Articles from This Issue, p. 1949
Supplementary Figure 5 from Metronomic administration of topotecan alone and in combination with docetaxel inhibits epithelial-mesenchymal transition in aggressive variant prostate cancers
Authors: MITRA GHOSH TARASWI , Mazumder Suman , Davis Joshua , YADAV JYOTI , AKINPELU AYUBA , ALNAIM AHMED , KUMAR HARISH , WALIAGHA RAZAN , Church Bird Allison E , Rais-Bahrami Soroush , Bird R. Curtis , Mistriotis Panagiotis , MISHRA AMARJIT , Yates Clayton C. , MITRA AMIT K , Arnold Robert D
Published: June 2023

Supplementary Fig. 5 shows Ingenuity pathway analysis (IPA) predictions for common DEGs among RNAseq vs. scRNAseq in all PCa cell lines

IPA predicted A) Diseases and biological pathways for common DGEs. Major pathways are cell invasion, movement, neoplasia, migration, transformation, metastatic and growth B) Causal network pathway for common DEGS include LY2109761 (TGF-β receptor inhibitor), IGF2R (receptor for both insulin-like growth factor 2), IL11RA (cytokine), SEMG2 (semenogelin proteins), CCR2 (chemokine receptor type 2), TRAF3IP3 (mediates cell growth by modulating the c-Jun N-terminal kinase signal transduction pathway), GGTI-2154 (inhibitor of geranylgeranyltransferase I ), L778123 (inhibitor of FPTase and GGPTase-I), TGFB1 and CXCL5. C) upstream regulators for common DEGs were THBF1, RAF1, AGT, ER receptor, OSM, SLC15A4, JUN, and IL1B D) Canonical pathways for common DEGs were s100 family, Hepatic fibrosis, Rho family, RHOGDI and integrin singling pathway.
Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer
Authors: Cecchini Michael , Zhang Janie Y. , Wei Wei , Sklar Jeffrey , Lacy Jill , Zhong Minghao , Kong Yong , Zhao Hongyu , DiPalermo Jassim , Devine Lesley , Stein Stacey M. , Kortmansky Jeremy , Johung Kimberly L. , Bindra Ranjit S. , LoRusso Patricia , Schalper Kurt A.
Published: June 2023

Purpose:

O6-methylguanine DNA methyltransferase (MGMT)-silenced tumors reveal sensitivity to temozolomide (TMZ), which may be enhanced by PARP inhibitors. Approximately 40% of colorectal cancer has MGMT silencing and we aimed to measure antitumoral and immunomodulatory effects from TMZ and olaparib in colorectal cancer.

Experimental Design:

Patients with advanced colorectal cancer were screened for MGMT promoter hypermethylation using methylation-specific PCR of archival tumor. Eligible patients received TMZ 75 mg/m2 days 1–7 with olaparib 150 mg twice daily every 21 days. Pretreatment tumor biopsies were collected for whole-exome sequencing (WES), and multiplex quantitative immunofluorescence (QIF) of MGMT protein expression and immune markers.

Results:

MGMT promoter hypermethylation was detected in 18/51 (35%) patients, 9 received study treatment with no objective responses, 5/9 had stable disease (SD) and 4/9 had progressive disease as best response. Three patients had clinical benefit: carcinoembryonic antigen reduction, radiographic tumor regression, and prolonged SD. MGMT expression by multiplex QIF revealed prominent tumor MGMT protein from 6/9 patients without benefit, while MGMT protein was lower in 3/9 with benefit. Moreover, benefitting patients had higher baseline CD8+ tumor-infiltrating lymphocytes. WES revealed 8/9 patients with MAP kinase variants (7 KRAS and 1 ERBB2). Flow cytometry identified peripheral expansion of effector T cells.

Conclusions:

Our results indicate discordance between MGMT promoter hypermethylation and MGMT protein expression. Antitumor activity seen in patients with low MGMT protein expression, supports MGMT protein as a predictor of alkylator sensitivity. Increased CD8+ TILs and peripheral activated T cells, suggest a role for immunostimulatory combinations.

Significance:

TMZ and PARP inhibitors synergize in vitro and in vivo in tumors with MGMT silencing. Up to 40% of colorectal cancer is MGMT promoter hypermethylated, and we investigated whether TMZ and olaparib are effective in this population. We also measured MGMT by QIF and observed efficacy only in patients with low MGMT, suggesting quantitative MGMT biomarkers more accurately predict benefit to alkylator combinations.
Clinical Outcomes and Genetic Analyses of Restrictive Cardiomyopathy in Children
Authors: Ishida Hidekazu , Narita Jun , Ishii Ryo , Suginobe Hidehiro , Tsuru Hirofumi , Wang Renjie , Yoshihara Chika , Ueyama Atsuko , Ueda Kazutoshi , Hirose Masaki , Hashimoto Kazuhisa , Nagano Hiroki , Kogaki Shigetoyo , Kuramoto Yuki , Miyashita Yohei , Asano Yoshihiro , Ozono Keiichi
Published: June 2023

BACKGROUND:

Restrictive cardiomyopathy in children is rare and outcomes are very poor. However, little information is available concerning genotype-outcome correlations.

METHODS:

We analyzed the clinical characteristics and genetic testing, including whole exome sequencing, of 28 pediatric restrictive cardiomyopathy patients who were diagnosed from 1998 to 2021 at Osaka University Hospital in Japan.

RESULTS:

The median age at diagnosis (interquartile range) was 6 (2.25–8.5) years. Eighteen patients received heart transplantations and 5 patients were on the waiting list. One patient died while waiting for transplantation. Pathologic or likely-pathogenic variants were identified in 14 of the 28 (50%) patients, including heterozygous
TNNI3
missense variants in 8 patients.
TNNT2
,
MYL2
, and
FLNC
missense variants were also identified. No significant differences in clinical manifestations and hemodynamic parameters between positive and negative pathogenic variants were detected. However, 2- and 5-year survival rates were significantly lower in patients with pathogenic variants (50% and 22%) compared with survival in patients without pathogenic variants (62% and 54%;
P
=0.0496, log-rank test). No significant differences were detected in the ratio of patients diagnosed at nationwide school heart disease screening program between positive and negative pathogenic variants. Patients diagnosed by school screening showed better transplant-free survival compared with patients diagnosed by heart failure symptoms (
P
=0.0027 in log-rank test).

CONCLUSIONS:

In this study, 50% of pediatric restrictive cardiomyopathy patients had pathogenic or likely-pathogenic gene variants, and
TNNI3
missense variants were the most frequent. Patients with pathogenic variants showed significantly lower transplant-free survival compared with patients without pathogenic variants.
Existence and the Problem of Aḥwāl: The Quiddity and Ontological Status of Existence in Avicenna and His Islamic Reception
Authors: Zamboni Francesco Omar
Published: June 2023

The Avicennian distinction between quiddity and existence opens the way to several derivative issues concerning the quiddity of existence (what existence is) and the ontological status of existence (whether and how existence is). This paper presents a fine-grained account of the positions and arguments developed by post-Avicennian authors on these matters, showing how the debates on states (aḥwāl) and grounding (taʿlīl) feed into the picture. The discussions on the quiddity of existence revolve around the features of its knowability and its connection to a ground (ʿilla), or lack thereof. As for the ontological status of existence, the standard idea of a clash between realism (existence is an extramental existent) and conceptualism (existence is a purely mental existent) calls for further refinement. First, realism itself encompasses two distinct positions when it comes to the relation between the second-order existence of existence and existence itself (sameness, additionality). Second, the tradition presents other doctrines not easily classifiable within the realism-conceptualism framework (the existential non-assertability of existence, the non-existence of existence).
Spatiotemporal evolution of ecological entropy in an ecologically vulnerable area
Authors: Hou Jingwei , Tan Yonghong , Hou Bo , Pang Xinyan
Published: June 2023

The spatiotemporal evolution of ecological entropy (EE) reflects the differences and correlations among the different elements (roads, rivers, land, etc.) and regions in an ecosystem. In this study, an index system for evaluating the EE in an ecologically vulnerable area in China from 2005 to 2020 is constructed according to the pressure–state–response model. Models of the EE and its gradient are constructed, and they are evaluated using GIS and remote sensing. The results show that except for the utilization rate of solid waste, the index values of EE have increased dramatically in the past 16 years. Investment in waste pollution control, GDP per capita, vegetation index in July, and utilization rate of solid waste make large contributions to the EE. The EEs on the edge of the ecologically vulnerable area increased from 2005 to 2020, indicating that the ecological environment in these areas has deteriorated year by year. The regions with the largest outflow of EE indicate that the EEs of these regions had a large impact on those of their surrounding regions. The regions with the largest inflow of EE indicate that the ecological security of these regions is relatively stable to the surrounding regions. Large EE gradients existed between adjacent regions show large rate of change and inflow and outflow of EE. The results contribute to alleviating the high entropy, reversing the ecological imbalance, enhancing the ecological benefits, and improving the environmental quality in an ecological entropy system. The present results offer decision support for ecological evaluation, protection, restoration, compensation, and security.