The glass is half-full: overestimating the quality of a novel environment is advantageous.
Ontology highlight
ABSTRACT:
SUBMITTER: Berger-Tal O
PROVIDER: S-EPMC3317990 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:During cancer progression genomes undergo point mutations as well as larger segmental changes. The latter include, among others, segmental deletions duplications, translocations and inversions.The result is a highly complex, patient-specific cancer karyotype. Using high-throughput technologies of deep sequencing and microarrays it is possible to interrogate a cancer genome and produce chromosomal copy number profiles and a list of breakpoints ("jumps") relative to the normal genome. This information is very detailed but local, and does not give the overall picture of the cancer genome. One of the basic challenges in cancer genome research is to use such information to infer the cancer karyotype. We present here an algorithmic approach, based on graph theory and integer linear programming, that receives segmental copy number and breakpoint data as input and produces a cancer karyotype that is most concordant with them. We used simulations to evaluate the utility of our approach, and applied it to real data.By using a simulation model, we were able to estimate the correctness and robustness of the algorithm in a spectrum of scenarios. Under our base scenario, designed according to observations in real data, the algorithm correctly inferred 69% of the karyotypes. However, when using less stringent correctness metrics that account for incomplete and noisy data, 87% of the reconstructed karyotypes were correct. Furthermore, in scenarios where the data were very clean and complete, accuracy rose to 90%-100%. Some examples of analysis of real data, and the reconstructed karyotypes suggested by our algorithm, are also presented.While reconstruction of complete, perfect karyotype based on short read data is very hard, a large fraction of the reconstruction will still be correct and can provide useful information.
| S-EPMC5688766 | biostudies-literature
Project description:Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin's lymphoma typically marked by an aggressive clinical course and a predilection for relapse. The B-cell receptor (BCR) signaling survival pathway is chronically activated in MCL, contributing to its pathogenesis. Ibrutinib is an inhibitor of Bruton's tyrosine kinase, a vital component of this pathway. This article details the current clinical experience with ibrutinib in the treatment of patients with MCL, including completed and published clinical trials and reviews potential adverse events (AEs) and pitfalls associated with ibrutinib therapy. Although most AEs experienced by patients treated with ibrutinib are mild, some can be severe and treatment limiting and may be attributed to off-target effects. Ibrutinib is a very promising agent for patients with MCL with notable response rates. However, when used as a single agent, around one third of patients relapse in the first 2 years of treatment. Recently reported combination therapies have shown significant activity. Emerging data evaluating potential mechanisms of drug resistance and the poor clinical outcomes after treatment failure are also discussed. Further understanding of resistance and its implications not only in relapsed disease but in the frontline setting are needed. Investigation of strategies to overcome resistance remains an area of high unmet clinical need. Evaluation of the impact of shorter treatment duration, effects on minimal residual disease, and incorporation of novel combinations are also warranted.
| S-EPMC4556969 | biostudies-literature
Project description:BackgroundClaims databases are generally considered inadequate for obesity research due to suboptimal capture of body mass index (BMI) measurements. This might not be true for bariatric surgery because of reimbursement requirements and changes in coding systems. We assessed the availability and validity of claims-based weight-related diagnosis codes among bariatric surgery patients.MethodsWe identified three nested retrospective cohorts of adult bariatric surgery patients who underwent adjusted gastric banding, Roux-en-Y gastric bypass, or sleeve gastrectomy between January 1, 2011 and June 30, 2018 using different components of OptumLabs® Data Warehouse, which contains linked de-identified claims and electronic health records (EHRs). We measured the availability of claims-based weight-related diagnosis codes in the 6-month preoperative and 1-year postoperative periods in the main cohort identified in the claims data. We created two claims-based algorithms to classify the presence of severe obesity (a commonly used cohort selection criterion) and categorize BMI (a commonly used baseline confounder or postoperative outcome). We evaluated their performance by estimating sensitivity, specificity, positive predictive value, negative predictive value, and weighted kappa in two sub-cohorts using EHR-based BMI measurements as the reference.ResultsAmong the 29,357 eligible patients identified using claims only, 28,828 (98.2%) had preoperative weight-related diagnosis codes, either granular indicating BMI ranges or nonspecific denoting obesity status. Among the 27,407 patients with granular preoperative codes, 12,346 (45.0%) had granular codes and 9355 (34.1%) had nonspecific codes in the 1-year postoperative period. Among the 3045 patients with both preoperative claims-based diagnosis codes and EHR-based BMI measurements, the severe obesity classification algorithm had a sensitivity 100%, specificity 71%, positive predictive value 100%, and negative predictive value 78%. The BMI categorization algorithm had good validity categorizing the last available preoperative or postoperative BMI measurements (weighted kappa [95% confidence interval]: preoperative 0.78, [0.76, 0.79]; postoperative 0.84, [0.80, 0.87]).ConclusionsClaims-based weight-related diagnosis codes had excellent validity before and after bariatric surgical operation but suboptimal availability after operation. Claims databases can be used for bariatric surgery studies of non-weight-related effectiveness and safety outcomes that are well-captured.
| S-EPMC7487952 | biostudies-literature
Project description: Not available
| S-EPMC8646454 | biostudies-literature
Project description: Not available
| S-EPMC9545087 | biostudies-literature
Project description:Congenital heart disease (CHD) is the most common congenital anomaly in newborn babies. Cardiac malformations have been produced in multiple experimental animal models, by perturbing selected molecules that function in the developmental pathways involved in myocyte specification, differentiation, or cardiac morphogenesis. In contrast, the precise genetic, epigenetic, or environmental basis for these perturbations in humans remains poorly understood. Over the past few decades, researchers have tried to bridge this knowledge gap through conventional genome-wide analyses of rare Mendelian CHD families, and by sequencing candidate genes in CHD cohorts. Although yielding few, usually highly penetrant, disease gene mutations, these discoveries provided 3 notable insights. First, human CHD mutations impact a heterogeneous set of molecules that orchestrate cardiac development. Second, CHD mutations often alter gene/protein dosage. Third, identical pathogenic CHD mutations cause a variety of distinct malformations, implying that higher order interactions account for particular CHD phenotypes. The advent of contemporary genomic technologies including single nucleotide polymorphism arrays, next-generation sequencing, and copy number variant platforms are accelerating the discovery of genetic causes of CHD. Importantly, these approaches enable study of sporadic cases, the most common presentation of CHD. Emerging results from ongoing genomic efforts have validated earlier observations learned from the monogenic CHD families. In this review, we explore how continued use of these technologies and integration of systems biology is expected to expand our understanding of the genetic architecture of CHD.
| S-EPMC3827691 | biostudies-literature
Project description:There has been a great deal of controversy in recent years about the potential role of dietary supplementation with long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) in the prevention of cardiovascular disease (CVD). Four recent meta-analyses have been published that evaluated randomized, controlled trial (RCT) data from studies that assessed the effects of supplemental n-3 PUFA intake on CVD endpoints. The authors of those reports reached disparate conclusions. This review explores the reasons informed experts have drawn different conclusions from the evidence, and addresses implications for future investigation. Although RCT data accumulated to date have failed to provide unequivocal evidence of CVD risk reduction with n-3 PUFA supplementation, many studies were limited by design issues, including low dosage, no assessment of n-3 status, and absence of a clear biological target or pathophysiologic hypothesis for the intervention. The most promising evidence supports n-3 PUFA supplementation for prevention of cardiac death. Two ongoing trials have enrolled high cardiovascular risk subjects with hypertriglyceridemia and are administering larger dosages of n-3 PUFA than employed in previous RCTs. These are expected to clarify the potential role of long-chain n-3 PUFA supplementation in CVD risk management.
| S-EPMC6073248 | biostudies-other
Project description:The prevailing theory on relationship judgments for interaction attributes suggests individuals tend to underestimate a romantic partner's expressions of compassionate love and that such underestimation is beneficial for the relationship. Yet, limited research has incorporated dyadic perspectives to assess how biased perceptions are associated with both partners' outcomes. In two daily studies of couples, we used distinct analytical approaches (Truth and Bias Model; Dyadic Response Surface Analysis) to inform perspectives on how biased perceptions are interrelated and predict relationship satisfaction. Consistent with prior research, people demonstrated an underestimation bias. However, there were differential effects of biased perceptions for actors versus partners: Underestimation predicted lower actor satisfaction but generally higher satisfaction for partners. Furthermore, we find evidence for complementarity effects: partners' directional biases were inversely related, and couples were more satisfied when partners had opposing patterns of directional bias. Findings help integrate theoretical perspectives on the adaptive role of biased relationship perceptions.
| S-EPMC11367802 | biostudies-literature
Project description:Broadband near-infrared (NIR) photonic materials have wide applications. Although extensive studies on rare-earth, transition-metal, and even semiconductor-activated materials have enabled the development of a rich NIR material pool, developing broadband and efficient photonic candidates covering the NIR I and II regions from 750 to 1500 nm has been met with limited success. Here, it is reported that a subnano Te cluster with a characteristic configuration different from that of the ion state may fill the aforementioned gap. Further, a strategy is proposed for the in situ generation and stabilization of Te clusters by tuning the cluster evolution in glass. A novel active photonic glass embedded with a Te cluster is fabricated; it exhibits intense and broadband short-wave NIR luminescence with a central wavelength at 1030 nm and a bandwidth exceeding 330 nm. Interestingly, the glass exhibited a full visible-spectrum conversion ability from 300 to 800 nm. The application of this unique broadband excitation feature for night vision and tissue penetration is demonstrated using a smartphone as the excitation source. These findings demonstrate a fundamental principle of cluster design in glass for creating new properties and provide a new direction for developing novel cluster-derived functional composite materials.
| S-EPMC10667836 | biostudies-literature
Project description:OBJECTIVES:Recent evidence suggests that half-dose thrombolysis for pulmonary embolism may provide similar efficacy with reduced bleeding risk compared with full-dose therapy, but comparative studies are lacking. We aimed to evaluate the effectiveness and safety of half-dose versus full-dose alteplase for treatment of pulmonary embolism. DESIGN:A retrospective cohort study comparing outcomes in patients receiving half-dose (50?mg) versus full-dose (100?mg) alteplase for pulmonary embolism. We used propensity score matching and sensitivity analyses to address confounding and hospital-level clustering. SETTING:Data from 420 hospitals obtained from the Premier Healthcare Database between January 2010 and December 2014. SUBJECTS:Adult critically ill patients with acute pulmonary embolism treated with IV alteplase therapy. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:This study included 3,768 patients: 699 (18.6%) in the half-dose and 3,069 (81.4%) in the full-dose group. At baseline, patients receiving half-dose alteplase required vasopressor therapy (23.3% vs 39.4%; p < 0.01) and invasive ventilation (14.3% vs 28.5%; p < 0.01) less often, compared with full dose. After propensity matching (n = 548 per group), half-dose alteplase was associated with increased treatment escalation (53.8% vs 41.4%; p < 0.01), driven mostly by secondary thrombolysis (25.9% vs 7.3%; p < 0.01) and catheter thrombus fragmentation (14.2% vs 3.8%; p < 0.01). Hospital mortality was similar (13% vs 15%; p = 0.3). There was no difference in cerebral hemorrhage (0.5% vs 0.4%; p = 0.67), gastrointestinal bleeding (1.6% vs 1.6%; p = 0.99), acute blood loss anemia (6.9% vs 4.6%; p = 0.11), use of blood products (p > 0.05 for all), or documented fibrinolytic adverse events (2.6% vs 2.8%; p = 0.82). CONCLUSIONS:Compared with full-dose alteplase, half-dose was associated with similar mortality and rates of major bleeding. Treatment escalation occurred more often in half-dose-treated patients. These results question whether half-dose alteplase provides similar efficacy with improved safety, and highlights the need for further study before use of half-dose alteplase therapy can be routinely recommended in patients with pulmonary embolism.
| S-EPMC6375681 | biostudies-literature