Miracle-dz/UniFAR-FTUs huggingface dataset:
Maternal Serum Lipid Trajectories and Association with Pregnancy Loss and Length of Gestation

Abstract Objective We characterized lipid trajectories and investigated lipids and rate of pregnancy lipid change with the risk of pregnancy loss or preterm delivery <37 weeks. Study Design In a secondary analysis of 337 women with one to two prior losses assigned to placebo in a randomized controlled trial at four centers (2007–2012), cholesterol, low- and high-density lipoprotein cholesterol (HDL-C), and triglycerides were measured up to 6 months prepregnancy (time 0) and pregnancy up to 7 visits. Trajectories were created using linear mixed models. Multivariable logistic regression with adjustment for maternal characteristics and cholesterol was performed. Results Lipids decreased from prepregnancy to 4 to 5 weeks, followed by an increase, and were biphasic or triphasic depending on the lipid component. Between 4 and 8 weeks, for every 1-unit increase in HDL-C, there was a 22% decreased odds of loss <14 weeks (odds ratio: 0.78; 95% confidence interval: 0.60, 0.99) and 24% decreased odds of loss or preterm delivery 14 to <37 weeks (odds ratio: 0.76; 95% confidence interval: 0.60, 0.96). Conclusion There were no associations with other lipid components or other time points. An impaired rise of HDL-C early in pregnancy may signal maladaptation to pregnancy that is associated with pregnancy loss or preterm delivery.
Cognitively Intact and Happy Life Expectancy in the US.

OBJECTIVES We examine the number of years to be lived with and without cognitive impairment and with high self-assessed quality of life (i.e., happiness) among a nationally representative sample of Americans age 65 years and older. Two key questions are addressed: Can people have a high quality of life despite being cognitively impaired? Which is longer: happy life expectancy or cognitively intact life expectancy? METHOD Data from nine waves of the Health and Retirement Study (1998-2014) were used to estimate transition probabilities into and out of cognitively intact/impaired-un/happy states, as well as to death. Recently extended Bayesian multistate life table methods were used to estimate age-specific cognitively intact and happy life expectancy net of sex, race/ethnicity, education, and birth cohort. RESULTS Happiness and cognitive impairment were shown to coexist in both the gross cross-tabulated data and in the life tables. Happy life expectancy is approximately 25 percent longer than cognitively intact life expectancy at age 65, and by age 85 happy life expectancy is roughly double cognitively intact life expectancy, on average. DISCUSSION Lack of cognitive impairment is not a necessary condition for happiness. In other words, people can have a high quality of life despite being cognitively impaired.
Diabetic nephropathy: an insight into molecular mechanisms and emerging therapies

ABSTRACT Introduction: Diabetic kidney disease (DKD) is a major cause of morbidity and mortality in diabetes and is the most common cause of proteinuric and non-proteinuric forms of end-stage renal disease (ESRD). Control of risk factors such as blood glucose and blood pressure is not always achievable or effective. Significant research efforts have attempted to understand the pathophysiology of DKD and develop new therapies. Areas covered: We review DKD pathophysiology in the context of existing and emerging therapies that affect hemodynamic and metabolic pathways. Renin-angiotensin system (RAS) inhibition has become standard care. Recent evidence for renoprotective activity of SGLT2 inhibitors and GLP-1 agonists is an exciting step forward while endothelin receptor blockade shows promise. Multiple metabolic pathways of DKD have been evaluated with varying success; including mitochondrial function, reactive oxygen species, NADPH oxidase (NOX), transcription factors (NF-B and Nrf2), advanced glycation, protein kinase C (PKC), aldose reductase, JAK-STAT, autophagy, apoptosis-signaling kinase 1 (ASK1), fibrosis and epigenetics. Expert opinion: There have been major advances in the understanding and treatment of DKD. SGLT2i and GLP-1 agonists have demonstrated renoprotection, with novel therapies under evaluation. Addressing the interaction between hemodynamic and metabolic pathways may help achieve prevention, attenuation or even reversal of DKD.
The Necrobiology of Mesenchymal Stromal Cells Affects Therapeutic Efficacy

Rapid progress is occurring in understanding the mechanisms underlying mesenchymal stromal cell (MSC)-based cell therapies (MSCT). However, the results of clinical trials, while demonstrating safety, have been varied in regard to efficacy. Recent data from different groups have shown profound and significant influences of the host inflammatory environment on MSCs delivered systemically or through organ-specific routes, for example intratracheal, with subsequent actions on potential MSC efficacies. Intriguingly in some models, it appears that dead or dying cells or subcellular particles derived from them, may contribute to therapeutic efficacy, at least in some circumstances. Thus, the broad cellular changes that accompany MSC death, autophagy, pre-apoptotic function, or indeed the host response to these processes may be essential to therapeutic efficacy. In this review, we summarize the existing literature concerning the necrobiology of MSCs and the available evidence that MSCs undergo autophagy, apoptosis, transfer mitochondria, or release subcellular particles with effector function in pathologic or inflammatory in vivo environments. Advances in understanding the role of immune effector cells in cell therapy, especially macrophages, suggest that the reprogramming of immunity associated with MSCT has a weighty influence on therapeutic efficacy. If correct, these data suggest novel approaches to enhancing the beneficial actions of MSCs that will vary with the inflammatory nature of different disease targets and may influence the choice between autologous or allogeneic or even xenogeneic cells as therapeutics.
Counteracting HIV-1 protease drug resistance: structural analysis of mutant proteases complexed with XV638 and SD146, cyclic urea amides with broad specificities.

The long-term therapeutic benefit of HIV antiretroviral therapy is still threatened by drug-resistant variants. Mutations in the S1 subsite of the protease are the primary cause for the loss of sensitivity toward many HIV protease inhibitors, including our first-generation cyclic urea-based inhibitors DMP323 and DMP450. We now report the structures of the three active-site mutant proteases V82F, I84V, and V82F/I84V in complex with XV638 and SD146, two P2 analogues of DMP323 that are 8-fold more potent against the wild type and are able to inhibit a broad panel of drug-resistant variants [Jadhav, P. K. , et al. (1997) J. Med. Chem. 40, 181-191]. The increased efficacy of XV638 and SD146 is due primarily to an increase in P2-S2 interactions: 30-40% more van der Waals contacts and two to four additional hydrogen bonds. Furthermore, because these new interactions do not perturb other subsites in the protease, it appears that the large complementary surface areas of their P2 substituents compensate for the loss of P1-S1 interactions and reduce the probability of selecting for drug-resistant variants.
Differential Proinflammatory Signature in Vestibular Migraine and Meniere Disease

Vestibular Migraine (VM) and Meniere's Disease (MD) are episodic vestibular syndromes defined by a set of associated symptoms such as tinnitus, hearing loss or migraine features during the attacks. Both conditions may show symptom overlap and there is no biological marker to distinguish them. Two subgroups of MD patients have been reported, according to their IL-1β profile. Therefore, considering the clinical similarity between VM and MD, we aimed to investigate the cytokine profile of MD and VM as a means to distinguish these patients. We have also carried out gene expression microarrays and measured the levels of 14 cytokines and 11 chemokines in 129 MD patients, 82 VM patients, and 66 healthy controls. Gene expression profile in peripheral blood mononuclear cells (PBMC) showed significant differences in MD patients with high and low basal levels of IL- 1β and VM patients. MD patients with high basal levels of IL- 1β (MDH) had overall higher levels of cytokines/chemokines when compared to the other subsets. CCL4 levels were significantly different between MDH, MD with low basal levels of IL- 1β (MDL), VM and controls. Logistic regression identified IL- 1β, CCL3, CCL22, and CXCL1 levels as capable of differentiating VM patients from MD patients (area under the curve = 0.995), suggesting a high diagnostic value in patients with symptoms overlap.
Prediction of VEGF-C as a Key Target of Pure Total Flavonoids From Citrus Against NAFLD in Mice via Network Pharmacology

Pure total flavonoids from Citrus (PTFC) effectively reduce the symptoms of non-alcoholic fatty liver disease (NAFLD). Our previous microarray analysis uncovered the alterations of important signaling pathways in the treatment of NAFLD with PTFC. However, the underlying core genes that might be targeted by PTFC, which play important roles in the progression of NALFD are yet to be identified. In this study, we predicted the vascular endothelial growth factor-C (VEGF-C) as potential key molecular target of PTFC against NAFLD via network pharmacology analysis. The network pharmacology approach presented here provided important clues for understanding the mechanisms of PTFC treatment in the development of NAFLD.
Training in pathology informatics: implementation at the University of Pittsburgh.

CONTEXT Pathology informatics is generally recognized as an important component of pathology training, but the scope, form, and goals of informatics training vary substantially between pathology residency programs. The Training and Education Committee of the Association for Pathology Informatics (API TEC) has developed a standard set of knowledge and skills objectives that are recommended for inclusion in pathology informatics training and may serve to standardize and formalize training programs in this area. OBJECTIVE The University of Pittsburgh (Pittsburgh, Pa) core rotation in pathology informatics includes most of these goals and is offered as an implementation model for pathology informatics training. DESIGN The core rotation in pathology informatics is a 3-week, full-time rotation including didactic sessions and hands-on laboratories. Topics include general desktop computing and the Internet, but the primary focus of the rotation is vocabulary and concepts related to enterprise and pathology information systems, pathology practice, and research. The total contact time is 63 hours, and a total of 19 faculty and staff contribute. Pretests and posttests are given at the start and end of the rotation. Performance and course evaluation data were collected for 3 years (a total of 21 residents). RESULTS The rotation implements 84% of the knowledge objectives and 94% of the skills objectives recommended by the API TEC. Residents scored an average of about 20% on the pretest and about 70% on the posttest for an average increase during the course of 50%. Posttest scores did not correlate with pretest scores or self-assessed computer skill level. The size of the pretest/posttest difference correlated negatively with the pretest scores and self-assessed computing skill level. CONCLUSIONS Pretest scores were generally low regardless of whether residents were familiar with desktop computing and productivity applications, indicating that even residents who are computer "savvy" have limited knowledge of pathology informatics topics. Posttest scores showed that all residents' knowledge increased substantially during the course and that residents who were computing novices were not disadvantaged. In fact, novices tended to have higher pretest/posttest differences, indicating that the rotation effectively supported initially less knowledgeable residents in "catching up" to their peers and achieving an appropriate competency level. This rotation provides a formal training model that implements the API TEC recommendations with demonstrated success.
How to foster informed decision making about food supplements: results from an international Delphi study

Abstract Food supplement use can have beneficial and detrimental effects, making informed decisions about supplement use important. How these decisions are made and which communication strategies can stimulate informed decision making is unclear. This study identified the important characteristics of (i) informed decision making about food supplement use and (ii) important factors indicating how to communicate about food supplements to foster informed decision making. An online three-round Delphi study was conducted. International experts within the field of (risk) communication about food supplements or related fields were recruited via email. The participants' age ranged from 25 to 69 years, and sample sizes for the three rounds were 38, 89 and 51, respectively. Experts indicated that for making an informed decision about food supplement use one needs to have knowledge of their positive and negative effects, the ability to compare these effects, knowing alternatives besides supplements, feeling informed, and feeling able (self-efficacious) to make the decision and making the decision voluntarily. Important communication strategies mentioned were: provision of information about positive and negative effects and the nature of these effects including scientific evidence, ensuring information is easily accessible, well ordered, tailored and provided by a trustworthy, credible and independent source.
Active Involvement of People with Dementia: A Systematic Review of Studies Developing Supportive Technologies

Although there are promising benefits of supportive technology in dementia care, use of these technologies is still limited. It is challenging for researchers and developers in this field to actively involve people with dementia in development. This review updates and builds on existing knowledge by including a contemporary and relevant perspective. This perspective was gained by including search words and search databases from the field of Human Computer Interaction (HCI) and Design, as these fields were expected to supply novel insights in the complex task of actively involving people with dementia in developing supportive technologies. A total of 49 out of 3456 studies were included which describe the development of a great variety of technologies. Often people with dementia were involved in the generative or evaluative phase of the development. Interviews and observations were most commonly used methods. In seven articles the people with dementia were co-designers. This literature review reflects that people with dementia can influence the development of technology in regards to content, design, and even the initial idea, although the impact on how they experience their own involvement remains largely unknown. There is a lack of specific knowledge on appropriate methods and materials for active involvement of people with dementia in supportive technology development, even when including articles from the field of HCI and Design. Future research is needed to further appreciate and improve the desired role of people with dementia in meaningful technology development.
Diagnosing Alternative Facts

This paper presents an approach to applying model-based diagnosis to the task of interpreting information from a wide variety of sources: text, video, meta-data, audio, etc. Much of the information contained in the sources is contradictory, incomplete, purposely deceptive or biased. People make critical decisions based on such murky information. By automating the construction of alternatives, we can design systems that support intelligence analysts and ordinary citizens in understanding the world. We have developed a preliminary version of our HCDX tool (hypothesis construction through diagnosis). We plan to distribute this tool as open source.
Neurocompensatory Effects of the Default Network in Older Adults

The hemispheric asymmetry reduction in older adults (HAROLD) is a neurocompensatory process that has been observed across several cognitive functions but has not yet been examined in relation to task-induced relative deactivations of the default mode network. The present study investigated the presence of HAROLD effects specific to neural activations and deactivations using a functional magnetic resonance imaging (fMRI) n-back paradigm. It was hypothesized that HAROLD effects would be identified in relative activations and deactivations during the paradigm, and that they would be associated with better 2-back performance. Forty-five older adults (M age = 63.8; range = 53–83) were administered a verbal n-back paradigm during fMRI. For each participant, the volume of brain response was summarized by left and right frontal regions of interest, and laterality indices (LI; i.e., left/right) were calculated to assess HAROLD effects. Group level results indicated that age was significantly and negatively correlated with LI (i.e., reduced left lateralization) for deactivations, but positively correlated with LI (i.e., increased left lateralization) for activations. The relationship between age and LI for deactivation was significantly moderated by performance level, revealing a stronger relationship between age and LI at higher levels of 2-back performance. Findings suggest that older adults may employ neurocompensatory processes specific to deactivations, and task-independent processes may be particularly sensitive to age-related neurocompensation.
Multimorbidity in older adults living with and beyond cancer.

PURPOSE OF REVIEW The current review draws attention to the need for longer term management of multiple conditions in older adults with cancer. RECENT FINDINGS Older people living with and beyond cancer are more likely than younger people to have higher prevalence of multimorbidity leading to an overall increase in illness and treatment burdens, limiting health-related quality of life (QoL), and capacity to self-manage. Older age presents a higher risk of cancer treatment side-effects and development or progression of other conditions, leading to worsening health, long-lasting functional problems, and social isolation. Although many prioritize functional independence and continuance of valued activities over survival, older people living with multimorbidity are more likely to experience poor physical functioning during and beyond cancer treatment. SUMMARY Cancer treatment decisions and survivorship plans should be developed in the context of other conditions and in line with the individual's priorities for continued QoL. More research is needed to guide service development and clinical practice in this important area.
Loss of ARID1A Expression Is an Early Molecular Event in Tumor Progression From Ovarian Endometriotic Cyst to Clear Cell and Endometrioid Carcinoma

Objectives ARID1A is a recently identified tumor suppressor participating in chromatin remodeling. Somatic inactivating mutations of ARID1A and loss of its expression occur frequently in ovarian clear cell and endometrioid carcinomas and in uterine endometrioid carcinomas. Because endometriotic epithelium is thought to be the cell of origin of most ovarian clear cell and endometrioid carcinomas, we undertook an analysis of ARID1A expression of these tumors arising within an endometriotic cyst (endometrioma). Materials and Methods Our immunohistochemical study set consisted of 47 endometriotic cysts containing clear cell carcinoma in 24 cases, well-differentiated ovarian endometrioid carcinoma in 20 cases, and mixed clear cell and endometrioid carcinoma in 3 cases. Results ARID1A loss was observed in 31 (66%) of 47 carcinomas; and therefore, these cases were informative for determining the temporal sequence of loss of ARID1A expression in tumor progression. In 16 of the 47 cases, ARID1A immunoreactivity was retained in both the endometriotic cyst and the carcinoma; and thus, these cases were not informative. All of the 31 informative cases showed loss of ARID1A immunoreactivity in the carcinoma and in the endometriotic cyst epithelium in direct continuity with the carcinoma but not in the cyst epithelium that was not adjacent to the tumor. Conclusions Loss of ARID1A function as shown by loss of expression, presumably due to mutations, is an early molecular event in the development of most ovarian clear cell and endometrioid carcinomas arising in endometriomas.
Salt complexation in block copolymer thin films

Ion complexation within cylinder-forming block copolymer thin films was found to affect the ordering process of the copolymer films during solvent annealing, significantly enhancing the long-range positional order. Small amounts of alkali halide or metal salts were added to PS-b-PEO, on the order of a few ions per chain, where the salt complexed with the PEO block. The orientation of the cylindrical microdomains strongly depended on the salt concentration and the ability of the ions to complex with PEO. The process shows large flexibility in the choice of salt used, including gold or cobalt salts, whereby well-organized patterns of nanoparticles can be generated inside the copolymer microdomains. By further increasing the amount of added salts, the copolymer remained highly ordered at large degrees of swelling and demonstrated long-range positional correlations of the microdomains in the swollen state, which holds promise as a route to addressable media.
The future of apolipoprotein E mimetic peptides in the prevention of cardiovascular disease.

PURPOSE OF REVIEW This review aims to discuss the recent developments in the area of apolipoprotein E (apoE) mimetics and their therapeutic potential for treating cardiovascular disease, the leading cause of mortality worldwide. RECENT FINDINGS Ongoing research efforts target the development of novel therapies that would not only reduce circulating levels of atherogenic lipoproteins, but could also increase high density lipoprotein cholesterol (HDL-C) levels and/or improve HDL function. Among them, synthetic peptides that mimic the structure of natural human apoE, a component of triglyceride-rich lipoproteins and HDL, have been designed and proven to be functionally similar to apoE. In specific, apoE mimetic peptides mediate hepatic clearance of circulating atherogenic lipoproteins, dramatically reduce plasma cholesterol, and lead to attenuation of atherosclerosis development in vivo. These peptides also exhibit pleiotropic antiatherogenic properties, such as macrophage cholesterol efflux capacity, as well as anti-inflammatory and antioxidative functions. SUMMARY ApoE mimetics are undergoing preclinical and clinical evaluation with promising results to date that render them attractive candidates in cardiovascular disease prevention and treatment.
Vitamin D deficiency and youth-onset diabetes in North India.

(1). It is also appreciated that the researcher has gone into the details of the study. The authors have rightly pointed out that vitamin D deficiency was more common in youth-onset diabetes (age less than 25 years) when compared with age, body mass index (BMI) and gender-matched healthy control population. Vitamin D deficiency was also found in healthy controls, but mean vitamin D was significantly lower in people with diabetes. We found that mean vitamin D levels were significantly lower when compared with healthy controls, but we did not demonstrate the relationship between vitamin D deficiency and development of diabetes, as it was not the mandate of the study. The author has rightly pointed out the difficulties in measuring vitamin D in blood samples. Compounds such as vitamin D, which are extremely hydrophobic, show many inherent difficulties for their measurement, also because there are two forms: viz 25(OH)D