Back to the Future: revisiting the contact hypothesis at Turkish and mixed non-profit organizations in Amsterdam

This paper revisits the contact hypothesis by assessing differences in generalized trust among participants of Turkish non-profit organizations and ethnically mixed organizations in Amsterdam. Most voluntary sector research takes the contact hypothesis at its core and assumes that the concentration of ethnic minorities in non-profit organizations is detrimental to learning generalized trust. These studies assume that diversity within organizations is better for developing generalized norms without examining participation in ethnically homogenous organizations. I address this gap in the literature by analysing the variance of generalized trust among organizations and their participants. I achieve this through the analysis of purposively designed survey data. The findings suggest that a contact mechanism at voluntary organizations is problematic and should not be asserted uncritically.     

医生集团之法律定位研究

由于医生“去编制化”“多点执业”制度的推进以及医疗市场需求、医生权利意识的觉醒,医生集团的产生具有现实基础。基于医疗服务的公益性、“医患社会团结连带”社会法法律关系性质、医生集团的自发性、协同性、自治性的内生原因以及社会成本目标控制,医生集团法律定位应为互益性非营利组织。其实现路径以从当前普遍存在的草根团队逐步过渡到法定互益性非营利组织为适当。     

Change the equation: improving science and mathematics education in the US

Change the Equation, a non-profit group of more than 100 corporate organizations, is committed to improving the state of mathematics and science education in the US.     

Protein arginine methylation promotes therapeutic resistance in human pancreatic cancer

Pancreatic cancer is a lethal disease with limited treatment options for cure. A high degree of intrinsic and acquired therapeutic resistance may result from cellular alterations in genes and proteins involved in drug transportation and metabolism, or from the influences of cancer microenvironment. Mechanistic basis for therapeutic resistance remains unclear and should profoundly impact our ability to understand pancreatic cancer pathogenesis and its effective clinical management. Recent evidences have indicated the importance of epigenetic changes in pancreatic cancer, including posttranslational modifications of proteins. We will review new knowledge on protein arginine methylation and its consequential contribution to therapeutic resistance of pancreatic cancer, underlying molecular mechanism, and clinical application of potential strategies of its reversal.     

医学研究生开展转录组学课程必要性的探讨

转录组学是生命科学领域的一门交叉型、发展快速的前沿性学科。随着高通量测序技术的迅猛发展,在收集、整合及数据挖掘的基础上全面系统的研究转录组成为可能。目前,利用转录组学的理论及技术研究疾病的转录组信息,系统全面阐明其基因表达调控规律,构建其基因调控网络,已经成为医学研究领域的热点。通过在医学研究生中开展转录组学这门课程,使研究生掌握其中的科研思维和方法,帮助研究生更清晰地认识疾病发生发展的分子机制,并通过学习这门课程提高研究生的科研能力和水平。     

CaP CURE Initiatives and Projects

CaP CURE was founded in 1993 to help find better treatments and a cure for prostate cancer. By reducing the time and complexity required to apply for funding, and by funding many first-time applicants, CaP CURE has attracted a large number of high-level investigators to the field of prostate cancer research. The organization's Therapy Consortium meets regularly to address major issues that impede progress in clinical development of new treatments for prostate cancer. CaP CURE has also sponsored an initiative to standardize clinical trial design scenarios for the clinical state of rising prostate-specific antigen and intends to present them to the Food and Drug Administration in partnership with the National Dialogue on Cancer. Finally, CaP CURE's efforts have resulted in a significant increase in federal funding of prostate cancer research programs.     

CaP CURE Initiatives and Projects

CaP CURE was founded in 1993 to help find better treatments and a cure for prostate cancer. By reducing the time and complexity required to apply for funding, and by funding many first-time applicants, CaP CURE has attracted a large number of high-level investigators to the field of prostate cancer research. The organization's Therapy Consortium meets regularly to address major issues that impede progress in clinical development of new treatments for prostate cancer. CaP CURE has also sponsored an initiative to standardize clinical trial design scenarios for the clinical state of rising prostate-specific antigen and intends to present them to the Food and Drug Administration in partnership with the National Dialogue on Cancer. Finally, CaP CURE's efforts have resulted in a significant increase in federal funding of prostate cancer research programs.     

A minimum version of log-rank test for testing the existence of cancer cure using relative survival data

Cancer survival is one of the most important measures to evaluate the effectiveness of treatment and early diagnosis. The ultimate goal of cancer research and patient care is the cure of cancer. As cancer treatments progress, cure becomes a reality for many cancers if patients are diagnosed early and get effective treatment. If a cure does exist for a certain type of cancer, it is useful to estimate the time of cure. For cancers that impose excess risk of mortality, it is informative to understand the difference in survival between cancer patients and the general cancer-free population. In population-based cancer survival studies, relative survival is the standard measure of excess mortality due to cancer. Cure is achieved when the survival of cancer patients is equivalent to that of the general population. This definition of cure is usually called the statistical cure, which is an important measure of burden due to cancer. In this paper, a minimum version of the log-rank test is proposed to test the equivalence of cancer patients' survival using the relative survival data. Performance of the proposed test is evaluated by simulation. Relative survival data from population-based cancer registries in SEER Program are used to examine patients' survival after diagnosis for various major cancer sites.     

Focus: Personalized Medicine: Crowdfunding for Personalized Medicine Research

Given the current funding situation of the National Institutes of Health, getting funding for rare disease research is extremely difficult. In light of the enormous potential for research in the rare diseases and the scarcity of research funding, we provide a case study of a novel successful crowdfunding approach at a non-profit organization called Rare Genomics Institute. We partner with biotechnology companies willing to donate their products, such as mouse models, gene editing software, and sequencing services, for which researchers can apply. First, we find that personal stories can be powerful tools to seek funding from sympathetic donors who do not have the same rational considerations of impact and profit. Second, for foundations facing funding restrictions, company donations can be a valuable tool in addition to crowdfunding. Third, rare disease research is particularly rewarding for scientists as they proceed to be pioneers in the field during their academic careers. Overall, by connecting donors, foundations, researchers, and patients, crowdfunding has become a powerful alternative funding mechanism for personalized medicine.     

Implementing the Precautionary Principle: Rigorous Science and Solid Ethics

The Precautionary Principle came out of European efforts to clean-up and protect marine ecosystems in the 1980s. Since then, several North American activities have elaborated on this approach in U.S. environmental programs. Unfortunately, US organizations and agencies have not developed strategies and guidelines for implementing the Precautionary Principle in either statutory or voluntary environmental programs. Recent interest in this approach from some members of the scientific, non-profit, and regulatory communities highlights the need to understand the history and conceptual basis of the Precautionary Principle. In this paper we address several of these issues. First, we summarize the pertinent US history of the Precautionary Principle. Next, we describe the scientific framework for the principle. Finally, we make the case that this provides unique opportunities for scientists to obtain meaning in their work by fulfilling what has been called the new Social Contract.     

化疗相关性闭经的影响因素及临床利弊

针对恶性肿瘤的化学治疗源于上世纪40年代Philips与Gilman第一次使用氮芥治疗恶性肿瘤,发展至今化疗在恶性肿瘤的治疗过程中已经取得了非常大的进步,成为恶性肿瘤的主要治疗方法之一。随着新药的逐渐研发和使用,已经使多数恶性肿瘤患者得到生存期的延长甚至是治愈。然而化疗导致的多种不良反应却日益受到越来越多的关注,如严重的骨髓抑制、心脏功能及结构的损伤、恶心、呕吐、腹泻、掉发等。化疗药物对多种身体多种器官系统都存在伤害,这其中因化疗引起的卵巢功能损伤导致的闭经是女性患者中最常见的,并且与治疗有关的不良事件之一。因化疗所导致的卵巢功能损害不仅严重影响患者的生活质量,而且还可能导致某些严重的疾病。因此探讨其发生规律和防治方法有重要意义。     

Redox proteomics gives insights into the role of oxidative stress in alkaptonuria

Alkaptonuria (AKU) is an ultra-rare metabolic disorder of the catabolic pathway of tyrosine and phenylalanine that has been poorly characterized at molecular level. As a genetic disease, AKU is present at birth, but its most severe manifestations are delayed due to the deposition of a dark-brown pigment (ochronosis) in connective tissues. The reasons for such a delayed manifestation have not been clarified yet, though several lines of evidence suggest that the metabolite accumulated in AKU sufferers (homogentisic acid) is prone to auto-oxidation and induction of oxidative stress. The clarification of the pathophysiological molecular mechanisms of AKU would allow a better understanding of the disease, help find a cure for AKU and provide a model for more common rheumatic diseases. With this aim, we have shown how proteomics and redox proteomics might successfully overcome the difficulties of studying a rare disease such as AKU and the limitations of the hitherto adopted approaches.     

民办非营利性医疗机构发展问题及对策

新医改方案中提出鼓励和引导社会资本发展医疗卫生事业,鼓励社会资本依法兴办非营利性医疗机构。发展民办医疗机构尤其是民办非营利性医疗机构对深化医药卫生体制改革具有重要意义。然而当前民办非营利性医疗机构的发展困难重重。试图从民间组织理论的视角出发,从社会环境、内部治理和外部监督管理等方面对民办非营利性医疗机构发展面临的问题进行分析,进而提出政策建议,希望为进一步发展民办非营利性医疗机构提供思路和经验借鉴。     

Clinical aspects of gastric cancer and Helicobacter pylori--screening, prevention, and treatment

Gastric cancer still represents a global health care burden, and in the absence of strategies implemented for early detection, the disease continues to have a dismal prognosis. Patients presenting with clinical manifestations of gastric cancer have limited options for cure. Thus, early detection and prevention play a key role in the fight against gastric cancer. Serologic-based test methods have the potential to detect a subset of patients at high risk of gastric cancer that require a close clinical and endoscopic follow-up. More data have been produced to support Helicobacter pylori eradication as an efficient strategy to prevent gastric cancer. Treatment options for patients with an advanced disease are still limited, but the introduction of new agents opens a more optimistic perspective for the future.     

早期胃癌血清特异标志物过氧化物酶4核酸适配体的筛选、鉴定与应用

胃癌是世界上死亡率第三的重大疾病,而在早期阶段却有着良好的治愈率和生存率。因此,找到针对早期胃癌的特异性标志物从而提高早期胃癌的检出率,是目前亟待解决的问题。在本实验室的早期研究中,发现过氧化物酶4（peroxiredoxin-4,PRDX4）有极大的潜能作为早期胃癌的特异性标志物,并且由于蛋白质结构的特殊性,能够分泌至血清中,为早期胃癌的无创化诊断提供了可能。本文为寻找血清中PRDX4蛋白的特异性适配体,通过消减-SELEX方法找到9种适配体。经特异性和亲和力分析后,证实其中Ap-EGACS-11在9种适配体中具有最高的特异性和亲和力。随后在适配体的验证研究中证实,相对于进展期胃癌病人血清、结直肠癌病人血清和正常人血清,Ap-EGACS-11对早期胃癌病人血清的检出率最高。该结果表明,PRDX4具有早期胃癌特异性血清标志物的潜能,且Ap-EGACS-11可直接作为早期胃癌的检测试剂。     

Is 2020 the year when primatologists should cancel fieldwork? A reply

The aim of this article is to explore the impact of coronavirus disease (COVID-19) pandemic on primate-related conservation work. The withdrawal of primatologists and conservation staff from field research can lead to a number of detrimental effects not just on conservation but also on local communities in low- and middle-income countries. Inequalities in access to health and financial insecurities may be drivers for the illegal wildlife trade and the lack of tourism and research activity may allow poachers to work with greater ease. The paper also looks at how conservation organizations and research bodies should modify their field protocols by developing robust occupational health policies that will not only make field work safer but also support local staff as they are likely to face the greatest threats to their physical health, psychological health, and economic loss from COVID-19. By adopting a One Health approach that considers the complex interactions between human and primate health, researchers will be able to find new ways of working not only to protect primates but understand how they adapt to the COVID-19 pandemic.     

Developing protocols for recombinant adeno-associated virus-mediated gene therapy in space

With the advent of the era of International Space Station (ISS) and Mars exploration, it is important more than ever to develop means to cure genetic and acquired diseases, which include cancer and AIDS, for these diseases hamper human activities. Thus, our ultimate goal is to develop protocols for gene therapy, which are suitable to humans on the earth as well as in space. Specifically, we are trying to cure the hemoglobinopathies, beta-thalassemia (Cooley's anemia) and sickle cell anemia, by gene therapy. These well-characterized molecular diseases serve as models for developing ex vivo gene therapy, which would apply to other disorders as well. For example, the procedure may become directly relevant to treating astronauts for space-anemia, immune suppression and bone marrow derived tumors, e.g. leukemia. The adeno-associated virus serotype 2 (AAV2) is a non-pathogenic human parvovirus with broad host-range and tissue specificity. Exploiting these characteristics we have been developing protocols for recombinant AAV2 (rAAV)-based gene therapy. With the rAAV constructs and hematopoietic stem cell (HSC) culture systems in hand, we are currently attempting to cure the mouse model of beta-thalassemia [C57BL/6- Hbbth/Hbbth, Hb(d-minor)] by HSC transplantation (HST) as well as by gene therapy. This paper describes the current status of our rAAV-gene therapy research.     

Peto's Paradox: evolution's prescription for cancer prevention

The evolution of multicellularity required the suppression of cancer. If every cell has some chance of becoming cancerous, large, long-lived organisms should have an increased risk of developing cancer compared with small, short-lived organisms. The lack of correlation between body size and cancer risk is known as Peto's paradox. Animals with 1000 times more cells than humans do not exhibit an increased cancer risk, suggesting that natural mechanisms can suppress cancer 1000 times more effectively than is done in human cells. Because cancer has proven difficult to cure, attention has turned to cancer prevention. In this review, similar to pharmaceutical companies mining natural products, we seek to understand how evolution has suppressed cancer to develop ultimately improved cancer prevention in humans.     

Telomerase-directed molecular therapeutics

The management of malignant disease remains one of the most challenging areas of modern medicine. The lifetime risk of developing cancer in the western world is estimated to be as high as 1 in 3. Traditionally, surgery, chemotherapy and radiotherapy have been the primary choice of treatment for patients with malignant tumours. Despite advances in the use and development of conventional cytotoxic agents, the cure rate remains disappointing in most patients with advanced disease of the common solid tumours. Consequently, the development of novel anti-cancer therapies is a high priority in cancer medicine. In recent years, a new generation of cancer therapies has emerged, based on a growing understanding of the molecular events that contribute to malignant transformation. A major difference between normal and cancer cells is the ability of cancer cells to multiply in an unrestricted and ungoverned fashion. In this context, there is considerable interest in elucidating the mechanisms that allow this unrestricted proliferation and that ultimately result in immortal cancer cells. It is now clear that the enzyme telomerase confers immortality on cells in most types of cancer. With the cancer cell reliant on telomerase for its survival, telomerase represents an extremely attractive mechanism-based target for the development of new cancer therapeutics.