Use of Long-Term Care Services by Older Persons with Limited English Proficiency.

Older migrants face special difficulties in the access and use of long-term care services and supports (LTSS). Our study was designed to examine how older persons with limited English proficiency (LEP) in two groups of migrants (Spanish or Chinese speaking) interact with the LTSS system. Focus groups were used to elicit information from members of these groups. We discovered Chinese elders were likely to believe that the LTSS services could, if managed properly, meet their needs, while the Spanish speakers were more skeptical. These differences were associated with the presence of trusted intermediaries among the Chinese elders who could represent their interests, while most Spanish speakers did not report having such intermediaries. In this way, trust, or lack of it, was uncovered as the key element defining older adults' interactions with the formal health and social service systems. Findings will be used to develop a modeling method that will allow us to analyze results in a manner that can be extended to use with other migrant groups.

Unsymmetrical Bisquinolines with High Potency against P. falciparum Malaria.

Quinoline-based scaffolds have been the mainstay of antimalarial drugs, including many artemisinin combination therapies (ACTs), over the history of modern drug development. Although much progress has been made in the search for novel antimalarial scaffolds, it may be that quinolines will remain useful, especially if very potent compounds from this class are discovered. We report here the results of a structure-activity relationship (SAR) study assessing potential unsymmetrical bisquinoline antiplasmodial drug candidates using in vitro activity against intact parasites in cell culture. Many unsymmetrical bisquinolines were found to be highly potent against both chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum parasites. Further work to develop such compounds could focus on minimizing toxicities in order to find suitable candidates for clinical evaluation.

Drug resistance in ALK-positiveNon-small cell lungcancer patients.

Patients are diagnosed as anaplastic lymphoma kinase (ALK) positive, i.e. exhibiting the ALK rearrangement, and comprise 3-7% of non-small-cell lung cancer (NSCLC) cases. Three generations of ALK inhibitors have been developed and used in targeted therapy, although there are still improving spaces of drug resistance at the initiation of each treatment. The current review discusses the pathophysiology of ALK-positive NSCLC and the role of three generations of ALK target inhibitors including crizotinib, ceritinib, alectinib and lorlatinib, as well as the mechanisms of the secondary resistance. We mainly focused on the point mutations that are the most important resistance-producing mechanism and most common form caused by each inhibitor. In addition, we examine the three-dimensional structure of ALK to understand the functional impact of these mutations and analyse the underlying molecular mechanisms of the resistance to each generation of ALK inhibitor to benefit the selection decision of the most rational therapy and improve therapeutic effects to the disease.

Oxalate contents of commonly used Chinese medicinal herbs.

OBJECTIVE: To assess the total and soluble oxalate contents of commonly used Chinese medicinal herbs. METHODS: Twenty-two Chinese medicinal herbs were extracted in both acid and water prior to determination of total and soluble oxalate, respectively. Oxalate was assayed in herbal extracts using a well-established enzymatic procedure. RESULTS: Among the 22 medicinal herbs, there was significant variation in oxalate content; Houttuynia cordata contained the highest amount of soluble oxalate (2146 mg/100 g) and Selaginella doederleinii contained the lowest amount (71 mg/ 100 g). CONCLUSION: The results indicated that different Chinese medicinal herbs, even from the same family, contain significantly different amounts of oxalate. In susceptible individuals, the use of medicinal herbs with the highest oxalate contents could increase risk of kidney stone formation.

Pregnancy Outcomes among Pregnant Persons after COVID-19 Vaccination: Assessing Vaccine Safety in Retrospective Cohort Analysis of U.S. National COVID Cohort Collaborative (N3C).

COVID-19 vaccines have been shown to be effective in preventing severe illness, including among pregnant persons. The vaccines appear to be safe in pregnancy, supporting a continuously favorable overall risk/benefit profile, though supportive data for the U.S. over different periods of variant predominance are lacking. We sought to analyze the association of adverse pregnancy outcomes with COVID-19 vaccinations in the pre-Delta, Delta, and Omicron SARS-CoV-2 variants' dominant periods (constituting 50% or more of each pregnancy) for pregnant persons in a large, nationally sampled electronic health record repository in the U.S. Our overall analysis included 311,057 pregnant persons from December 2020 to October 2023 at a time when there were approximately 3.6 million births per year. We compared rates of preterm births and stillbirths among pregnant persons who were vaccinated before or during pregnancy to persons vaccinated after pregnancy or those who were not vaccinated. We performed a multivariable Poisson regression with generalized estimated equations to address data site heterogeneity for preterm births and unadjusted exact models for stillbirths, stratified by the dominant variant period. We found lower rates of preterm birth in the majority of modeled periods (adjusted incidence rate ratio [aIRR] range: 0.42 to 0.85; p-value range: <0.001 to 0.06) and lower rates of stillbirth (IRR range: 0.53 to 1.82; p-value range: <0.001 to 0.976) in most periods among those who were vaccinated before or during pregnancy compared to those who were vaccinated after pregnancy or not vaccinated. We largely found no adverse associations between COVID-19 vaccination and preterm birth or stillbirth; these findings reinforce the safety of COVID-19 vaccination during pregnancy and bolster confidence for pregnant persons, providers, and policymakers in the importance of COVID-19 vaccination for this group despite the end of the public health emergency.

A global resource to translational medicine: the International Park of Translational Medicine and BioMedicine (IPTBM).

Translational science consists of research and development that integrates multiple resources to expedite the successful treatment of disease. The International Park of Translational BioMedicine (IPTBM) is currently being developed within the interface between Zhejiang Province and Shanghai Municipality. IPTBM has been designed to pioneer comprehensive biomedical research that spans the continuum from the education of young scientists to providing the infrastructure necessary for clinical testing and direct observation to better understand human biology while promoting viable commercial results within a vibrant biotechnology community. IPTBM's goal is to attract global partners organized around five fundamental pillars: 1) Institutional Development, 2) Project Implementation, 3) Development and Production, 4) Investment and 5) Regulatory Clusters to address the needs of an international platform of scientists, institutes, universities, commercial enterprises, investors, politicians, and other stakeholders. The IPTBM differs from existing models including CTSA's (US, NIH) technology because of its comprehensive approach to merge education, research, innovation, and development to translate clinical and public health needs into target-oriented and cost-efficient projects.

Who is pregnant? Defining real-world data-based pregnancy episodes in the National COVID Cohort Collaborative (N3C).

Objectives: To define pregnancy episodes and estimate gestational age within electronic health record (EHR) data from the National COVID Cohort Collaborative (N3C). Materials and Methods: We developed a comprehensive approach, named Hierarchy and rule-based pregnancy episode Inference integrated with Pregnancy Progression Signatures (HIPPS), and applied it to EHR data in the N3C (January 1, 2018-April 7, 2022). HIPPS combines: (1) an extension of a previously published pregnancy episode algorithm, (2) a novel algorithm to detect gestational age-specific signatures of a progressing pregnancy for further episode support, and (3) pregnancy start date inference. Clinicians performed validation of HIPPS on a subset of episodes. We then generated pregnancy cohorts based on gestational age precision and pregnancy outcomes for assessment of accuracy and comparison of COVID-19 and other characteristics. Results: We identified 628 165 pregnant persons with 816 471 pregnancy episodes, of which 52.3% were live births, 24.4% were other outcomes (stillbirth, ectopic pregnancy, abortions), and 23.3% had unknown outcomes. Clinician validation agreed 98.8% with HIPPS-identified episodes. We were able to estimate start dates within 1 week of precision for 475 433 (58.2%) episodes. 62 540 (7.7%) episodes had incident COVID-19 during pregnancy. Discussion: HIPPS provides measures of support for pregnancy-related variables such as gestational age and pregnancy outcomes based on N3C data. Gestational age precision allows researchers to find time to events with reasonable confidence. Conclusion: We have developed a novel and robust approach for inferring pregnancy episodes and gestational age that addresses data inconsistency and missingness in EHR data.

Computational modeling and epidemiologic approaches: a new section of the Journal of Translational Medicine.

A new section of the Journal of Translational Medicine is being introduced to encourage rapid communication of methods and results that utilize computational modeling and epidemiologic approaches in translational medicine. The focus will be on population-based studies that extend towards more molecular level analysis. Submission of studies involving methods development is encouraged where actual application and results can be shown in the healthcare and life sciences domains.

Expanding the perspective of translational medicine: the value of observational data.

In 2003, the Journal of Translational Medicine was launched to foster the publication of high quality research in both "bench-to-bedside" as well as ex vivo human observation. In spite of the success of several large-scale observational studies, e.g. Framingham Heart Study, the opportunity to expand upon the ex vivo human observation has remained limited within the field of translational medicine. We believe that this presents a significant opportunity that merits consideration in both the planning and analysis of large scale observational studies and can contribute greatly to expanding our approaches in translational medicine.

The application of observational data in translational medicine: analyzing tobacco-use behaviors of adolescents.

BACKGROUND: Translational Medicine focuses on "bench to bedside", converting experimental results into clinical use. The "bedside to bench" transition remains challenging, requiring clinicians to define true clinical need for laboratory study. In this study, we show how observational data (an eleven-year data survey program on adolescent smoking behaviours), can identify knowledge gaps and research questions leading directly to clinical implementation and improved health care. We studied gender-specific trends (2000-2010) in Italian students to evaluate the specific impact of various anti-smoking programs, including evaluation of perceptions of access to cigarettes and health risk. METHODS: The study used, ESPAD-Italia® (European School Survey Project on Alcohol and other Drugs), is a nationally representative sample of high-school students. The permutation test for joinpoint regression was used to calculate the annual percent change in smoking. Changes in smoking habits by age, perceived availability and risk over a 11-year period were tested using a gender-specific logistic model and a multinomial model. RESULTS: Gender-stratified analysis showed 1) decrease of lifetime prevalence, then stabilization (both genders); 2) decrease in last month and occasional use (both genders); 3) reduction of moderate use (females); 4) no significant change in moderate use (males) and in heavy use (both genders). Perceived availability positively associates with prevalence, while perceived risk negatively associates, but interact with different effects depending on smoking patterns. In addition, government implementation of public policies concerning access to tobacco products in this age group during this period presented a unique background to examine their specific impact on behaviours. CONCLUSION: Large observational databases are a rich resource in support of translational research. From these observations, key clinically relevant issues can be identified and form the basis for further clinical studies. The ability to identify patterns of behaviour and gaps in available data translates into new experiments, but also impacts development of public policy and reveals patterns of clinical reality. The observed global decrease in use is countered by stabilization in number of heavy smokers. Increased cigarette cost has not reduced use. While perceived risk of smoking may prevent initial experimentation, how government policies impact the perception of risk is not easily quantifiable.

Acute probiotic ingestion reduces gastrointestinal oxalate absorption in healthy subjects.

Both a high dietary oxalate intake and increased intestinal absorption appear to be major causes of elevated urine oxalate, a risk factor for kidney stone formation. A number of recent studies have assessed whether daily ingestion of a probiotic containing oxalate-degrading bacteria could lead to sufficient gut colonization to increase oxalate degradation, thereby reducing urinary oxalate. In contrast, the present study assessed whether simultaneous ingestion of oxalate-degrading probiotic bacteria with a 176 mg oxalate load could lead to decreased urinary oxalate in a population of 11 healthy non-stone formers (8 females, 3 males), aged 21-45 years. The results indicated that both the single and double doses of VSL#3(®) probiotic solutions were effective in reducing urinary oxalate and estimated oxalate absorption with no significant difference between the two probiotic doses. The timing of the reduction in urinary oxalate suggested a small intestinal and possibly gastric reduction in oxalate absorption. Similar to what had been reported for chronic or daily probiotic ingestion, individuals characterized by high oxalate absorption were most likely to experience clinically significant reductions in urinary oxalate in response to acute probiotic ingestion.

Who is pregnant? defining real-world data-based pregnancy episodes in the National COVID Cohort Collaborative (N3C).

Objective: To define pregnancy episodes and estimate gestational aging within electronic health record (EHR) data from the National COVID Cohort Collaborative (N3C). Materials and Methods: We developed a comprehensive approach, named H ierarchy and rule-based pregnancy episode I nference integrated with P regnancy P rogression S ignatures (HIPPS) and applied it to EHR data in the N3C from 1 January 2018 to 7 April 2022. HIPPS combines: 1) an extension of a previously published pregnancy episode algorithm, 2) a novel algorithm to detect gestational aging-specific signatures of a progressing pregnancy for further episode support, and 3) pregnancy start date inference. Clinicians performed validation of HIPPS on a subset of episodes. We then generated three types of pregnancy cohorts based on the level of precision for gestational aging and pregnancy outcomes for comparison of COVID-19 and other characteristics. Results: We identified 628,165 pregnant persons with 816,471 pregnancy episodes, of which 52.3% were live births, 24.4% were other outcomes (stillbirth, ectopic pregnancy, spontaneous abortions), and 23.3% had unknown outcomes. We were able to estimate start dates within one week of precision for 431,173 (52.8%) episodes. 66,019 (8.1%) episodes had incident COVID-19 during pregnancy. Across varying COVID-19 cohorts, patient characteristics were generally similar though pregnancy outcomes differed. Discussion: HIPPS provides support for pregnancy-related variables based on EHR data for researchers to define pregnancy cohorts. Our approach performed well based on clinician validation. Conclusion: We have developed a novel and robust approach for inferring pregnancy episodes and gestational aging that addresses data inconsistency and missingness in EHR data.

Synovial fluid proteins differentiate between the subtypes of juvenile idiopathic arthritis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of inflammatory diseases, and no clinically useful prognostic markers to predict disease outcome in children with JIA are currently available. Synovial fluid likely reflects the proteins present in the inflamed synovium. The purpose of this study was to delineate the synovial fluid proteome and determine whether protein expression differs in the different subtypes of JIA. METHODS: Synovial fluid samples obtained from children with oligoarticular JIA, polyarticular JIA, or systemic JIA were compared. Two-dimensional gel electrophoresis for protein separation and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry and quadripole time-of-flight mass spectrometry for protein identification were used for this study. Synovial fluid cells were analyzed by polymerase chain reaction (PCR) for the presence of haptoglobin messenger RNA (mRNA). RESULTS: The synovial fluid proteome of the samples was delineated. The majority of proteins showed overexpression in JIA synovial fluid as compared with noninflammatory control samples. There were 24 statistically significantly differentially expressed spots (>2-fold change; P < 0.05) between the subtypes of JIA. PCR analysis revealed haptoglobin mRNA, suggesting that haptoglobin is locally produced in an inflamed joint in JIA. CONCLUSION: Despite the similar histologic appearance of inflamed joints in patients with different subtypes of JIA, there are differences in protein expression according to the subtype of JIA. Haptoglobin is differentially expressed between the subtypes of JIA and is locally produced in an inflamed joint in JIA. Haptoglobin and other differentially expressed proteins may be potential biomarkers in JIA.

DW4TR: A Data Warehouse for Translational Research.

The linkage between the clinical and laboratory research domains is a key issue in translational research. Integration of clinicopathologic data alone is a major task given the number of data elements involved. For a translational research environment, it is critical to make these data usable at the point-of-need. Individual systems have been developed to meet the needs of particular projects though the need for a generalizable system has been recognized. Increased use of Electronic Medical Record data in translational research will demand generalizing the system for integrating clinical data to support the study of a broad range of human diseases. To ultimately satisfy these needs, we have developed a system to support multiple translational research projects. This system, the Data Warehouse for Translational Research (DW4TR), is based on a light-weight, patient-centric modularly-structured clinical data model and a specimen-centric molecular data model. The temporal relationships of the data are also part of the model. The data are accessed through an interface composed of an Aggregated Biomedical-Information Browser (ABB) and an Individual Subject Information Viewer (ISIV) which target general users. The system was developed to support a breast cancer translational research program and has been extended to support a gynecological disease program. Further extensions of the DW4TR are underway. We believe that the DW4TR will play an important role in translational research across multiple disease types.

From Personalized Medicine to Personalized Aging Services.

As medical models become more ubiquitous in developing strategies to provide long-term care services and support (LTSS), we need to ask whether these models adequately account for sources of diversity and disadvantage that affect access to and use of services by older adults. Medical models typically focus on categorizing information about the individual in order to clearly define current health status and appropriate treatment. Any individual, however, reflects the sum of their life experiences. Therefore, this medicalization approach can miss key factors in determining health outcomes including social determinants of health. Just as importantly, this approach can miss issues of values, beliefs, and assumptions that older adults can bring into the encounter with service providers. This issue is especially important when dealing with older migrant communities. Beliefs and attitudes shaped in their place of origin, as well as the migration experience, can influence levels of trust and resulting decisions regarding the use of LTSS. We need to integrate an understanding of how these beliefs and attitudes affect decision making into any model designed to improve the lives of older persons.

Probiotic-induced reduction of gastrointestinal oxalate absorption in healthy subjects.

Both a high dietary oxalate intake and increased intestinal absorption appear to be major causes of elevated urine oxalate, a risk factor for kidney stone formation. By favorably altering the gastrointestinal bacterial population, probiotics have the potential to lower oxalate absorption/urinary excretion. This study assessed whether a 4-wk daily consumption of a commercially available probiotic by 11 healthy volunteers (8 females, 3 males), aged 21-36 y, would decrease oxalate absorption. The study involved the ingestion of a probiotic (VSL#3) for a 4 wk period followed by a 4 wk washout period. Oxalate load tests, providing a total of 80 mg oxalate, were conducted at baseline (pre-probiotic), and after the probiotic and washout periods. In the total subject population, mean total 22 h oxalate absorption at baseline (30.8 %) was significantly higher than after the probiotic (11.6 %) and washout (11.5 %) periods. However, four subjects identified as high oxalate absorbers at baseline had a particularly marked probiotic-induced reduction in oxalate absorption, which largely accounted for the reduction observed in the total subject population. The overall data suggested that in individuals characterized by high oxalate absorption levels, VSL#3 ingestion has the potential to reduce gastrointestinal oxalate absorption, which could decrease risk of kidney stones and other disorders related to hyperoxaluria.

Shifting the Paradigm: The Dress-COV Telegram Bot as a Tool for Participatory Medicine.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic management is limited by great uncertainty, for both health systems and citizens. Facing this information gap requires a paradigm shift from traditional approaches to healthcare to the participatory model of improving health. This work describes the design and function of the Doing Risk sElf-assessment and Social health Support for COVID (Dress-COV) system. It aims to establish a lasting link between the user and the tool; thus, enabling modeling of the data to assess individual risk of infection, or developing complications, to improve the individual's self-empowerment. The system uses bot technology of the Telegram application. The risk assessment includes the collection of user responses and the modeling of data by machine learning models, with increasing appropriateness based on the number of users who join the system. The main results reflect: (a) the individual's compliance with the tool; (b) the security and versatility of the architecture; (c) support and promotion of self-management of behavior to accommodate surveillance system delays; (d) the potential to support territorial health providers, e.g., the daily efforts of general practitioners (during this pandemic, as well as in their routine practices). These results are unique to Dress-COV and distinguish our system from classical surveillance applications.

Translation of Digital Health Technologies to Advance Precision Medicine: Informing Regulatory Science.

The proliferation of digital technologies and the application of sophisticated data analysis techniques are increasingly viewed as having the potential to transform translational research and precision medicine. While digital technologies are rapidly applied in innovative ways to develop new diagnostics and therapies, the ultimate approval and adoption of these emerging methods presents several scientific and regulatory challenges. To better understand and address these regulatory science gaps, a working group of the Clinical and Translational Science Awards Program convened the Regulatory Science to Advance Precision Medicine Forum focused on digital health, particularly examining gaps in the use, validation, and interpretation of data from sensors that collect and tools that analyze digital biomarkers. The key findings and recommendations provided here emerged from the Forum and include the need to enhance areas related to data standards, data quality and validity, knowledge management, and building trust between all stakeholders.

Hypertension is an independent predictor of survival disparity between African-American and white breast cancer patients.

The objective of this study was to determine whether comorbidity, or pre-existing conditions, can account for some of the disparity in survival between African-American and white breast cancer patients. A historical cohort study was conducted of 416 African-American and 838 white women diagnosed with breast cancer between 1973 and 1986, and followed through 1999 in the Kaiser Permanente Northern California Medical Care Program. Information on comorbidity, tumor characteristics and breast cancer treatment was obtained from medical records, and Surveillance, Epidemiology and End Results, Northern California Cancer Center Registry. Associations between comorbidity and survival were analyzed with multiple Cox proportional hazards regression. Over a mean follow-up of 9 years, African Americans had higher overall crude mortality than whites: 165 (39.7%) versus 279 (33.3%), respectively. When age, race, tumor characteristics and breast cancer treatment were controlled, the presence of hypertension was associated with all cause survival [hazard ratio (HR) = 1.33, 95% confidence intervals (CI) 1.07-1.67] and it accounted for 30% of racial disparity in this outcome. Hypertension-augmented Charlson Comorbidity Index was a significant predictor of survival from all causes (HR = 1.32, 95%CI 1.18-1.49), competing causes (HR = 1.52, 95%CI 1.32-1.76) and breast cancer specific causes (HR = 1.18, 95%CI 1.03-1.35). In conclusion, hypertension has prognostic significance in relation to survival disparity between African-American and white breast cancer patients. If our findings are replicated in contemporary cohorts, it may be necessary to include hypertension in the Charlson Comorbidity Index and other comorbidity measures.