Miracle-dz/UniFAR-FTUs huggingface dataset:
Low dose positron emission tomography emulation from decimated high statistics: A clinical validation study.

PURPOSE The fundamental nature of positron emission tomography (PET), as an event detection system, provides some flexibility for data handling, including retrospective data manipulation. The reorganization of acquisition data allows the emulation of new scans arising from identical radiotracer spatial distributions, but with different statistical compositions, and is especially useful for evaluating the stability and reproducibility of reconstruction algorithms or when investigating extremely low count conditions. This approach is ubiquitous in the research literature but has only been validated, from the point of view of the noise properties, with numerical simulations and phantom data. We present here the first experiment comparing PET images of the same human subjects generated with two separate injections of radiotracer, using actual low dose (LD) data to validate a randomly decimated emulation from a standard dose scan. A key point of the work is focused on the randoms fractions, which scale differently than the trues at varying activity levels. METHODS Eleven patients with non-small cell lung cancer were enrolled in the study. Each imaging session consisted of two independent FDG-PET/CT scans: a LD scan followed by a standard dose (SD) scan. Images were first reconstructed, using filtered back-projection (FBP) and OSEM incorporating time-of-flight information and point-spread function modeling (PSFTOF), from the LD and SD datasets comprising all counts from each scanned bed position. The number of true counts was recorded for all LD scans, and independent, count-matched emulations (ELD) were reconstructed from the SD data. Noise distribution within the liver and standardized uptake value reproducibility within a population of contoured, tracer-avid lesion volumes were evaluated across scans and statistics. RESULTS The randoms fraction estimates were 17.4 ± 1.6% (14.9-19.4) in the LD data and 42 ± 2.3% (37.1-45.5) in the SD data. Eleven lesions were identified and volumes of interest were generated with a 50% threshold isocontour for each lesion, in every image. The distributions of metabolic volumes, means and maxima defined by the contoured volumes-of-interest (VOIs) were similar between the LD and SD sets. A two-tailed, matched t-test was performed on the populations of region statistics for both LD and ELD reconstructions, and the t-statistics were 1.1 (P = 0.267) and -0.22 (P = 0.828) for the background liver VOIs and -0.54 (P = 0.603) and 0.23 (P = 0.821) for the lesion VOIs, for FBP and PSFTOF respectively. In every test, the null hypothesis that the two populations had the same mean could not be rejected at the 5% significance level. CONCLUSIONS Our results demonstrate that clinical LD PET scans can indeed be accurately emulated by the statistical decimation of standard dose scans, and this was achieved through validation by images generated with unbiased random coincidence estimations.
Targeted blockade of HSP90 impairs DNA-damage response proteins and increases the sensitivity of ovarian carcinoma cells to PARP inhibition

ABSTRACT Pharmacological inhibition of PARP is a promising approach in treating high grade serous ovarian carcinoma (HGSOC). PARP inhibitors (PARPi) are most active in patients with defects in DNA damage repair (DDR) mechanisms, such as alterations in expression/function of DNA repair and homologous recombination (HR) genes/proteins, including BRCA1 and BRCA2. Benefit of PARPi could be extended towards HR-proficient patients by combining PARPi with agents that functionally abrogate HR. An attractive molecular target for this purpose is heat shock protein 90 (HSP90), which mediates the maturation and stability of several key proteins required for DDR. Here, we tested the hypothesis that targeted inhibition of HSP90 with a small-molecule inhibitor ganetespib would sensitize non-BRCA mutant ovarian carcinoma (OC) cells to PARP inhibition by talazoparib. We used commercially available cell lines, along with several novel HGSOC OC cell lines established in our laboratory. Ganetespib treatment destabilized HSP90 client proteins involved in DNA damage response and cell cycle checkpoint, and disrupted γ-irradiation-induced DNA repair. The effects of the combination of ganetespib and talazoparib on OC cell viability and survival were also analyzed, and among the non-BRCA mutant cell lines analyzed, the combination was synergistic in several cell lines (OVCAR-3, OC-1, OC-16). Together, our data suggest that ganetespib-mediated inhibition of HSP90 effectively disrupts critical DDR pathway proteins and may sensitize OC cells without ‘BRCAness’ to PARPi. From a clinical perspective, this suggests that HSP90 inhibition has the potential to sensitize some HGSOC patients without HR pathway alterations to PARPi, and potentially other DNA-damage inducing agents.
Mapping Local Conformational Landscapes of Proteins in Solution

The ability of proteins to adopt multiple conformational states is essential to their function and elucidating the details of such diversity under physiological conditions has been a major challenge. Here we present a generalized method for mapping protein population landscapes by NMR spectroscopy. Experimental NOESY spectra are directly compared to a set of expectation spectra back-calculated across an arbitrary conformational space. Signal decomposition of the experimental spectrum then directly yields the relative populations of local conformational microstates. In this way, averaged descriptions of conformation can be eliminated. As the method quantitatively compares experimental and expectation spectra, it inherently delivers an R-factor expressing how well structural models explain the input data. We demonstrate that our method extracts sufficient information from a single 3D NOESY experiment to perform initial model building, refinement and validation, thus offering a complete de novo structure determination protocol.
Two‐stage analysis for selecting fixed numbers of features in omics association studies

One of main roles of omics‐based association studies with high‐throughput technologies is to screen out relevant molecular features, such as genetic variants, genes, and proteins, from a large pool of such candidate features based on their associations with the phenotype of interest. Typically, screened features are subject to validation studies using more established or conventional assays, where the number of evaluable features is relatively limited, so that there may exist a fixed number of features measurable by these assays. Such a limitation necessitates narrowing a feature set down to a fixed size, following an initial screening analysis via multiple testing where adjustment for multiplicity is made. We propose a two‐stage screening approach to control the false discovery rate (FDR) for a feature set with fixed size that is subject to validation studies, rather than for a feature set from the initial screening analysis. Out of the feature set selected in the first stage with a relaxed FDR level, a fraction of features with most statistical significance is firstly selected. For the remaining feature set, features are selected based on biological consideration only, without regard to any statistical information, which allows evaluating the FDR level for the finally selected feature set with fixed size. Improvement of the power is discussed in the proposed two‐stage screening approach. Simulation experiments based on parametric models and real microarray datasets demonstrated substantial increment in the number of screened features for biological consideration compared with the standard screening approach, allowing for more extensive and in‐depth biological investigations in omics association studies.
Caregiver's social relations and children's oral health in a low-income urban setting.

Aim This paper seeks to describe the social networks and support available to caregivers of young children, and their links to behavioural and clinical dimensions of children's oral health. Design A cross-sectional study was conducted on the third wave of a cohort of 612 child-caregiver pairs of the Detroit Dental Health Project (DDHP). Caregivers and their children came to a central location in Detroit where they completed interviewer-administered questionnaires, health and nutritional assessments, and received an oral examination. Caregiver's social networks were measured using the hierarchical mapping technique. Child's oral health measures included previous dental visits and untreated decay. Results Caregivers reported an average network size of approximately seven people, who on average were 37 years old. Ninety percent of members in the network lived within an hour's drive, and contact frequency occurred on average between once a week and daily. Caregivers reported receiving emotional support most frequently and money support least frequently. Caregivers with larger networks had a slightly higher probability of reporting frequent errand support. Child's age interacted with money support to predict whether or not the child had visited the dentist since the last DHHP visit and to predict the number of untreated decayed surfaces. Conclusions The association between network characteristics and types of social support appear to be limited. There are no main effects of caregiver social network characteristics or support type on child's oral health. Having no money support appears most influential on children's oral health depending on their age.
Strategy use and verbal memory in older adults: The role of intellectual functioning and the preferential impact of semantic clustering

Abstract Objective: The relative importance of various mechanisms supporting declarative verbal memory among older adults remains uncertain. The present study examined the impact of strategy use (specifically semantic clustering) versus other variables known to impact memory performance (age, sex, education, FSIQ, processing speed, and executive functioning) on verbal memory functioning among healthy older adults. Methods: Healthy older adults from the California Verbal Learning Test, Second Edition standardization sample were selected (N = 242). Relationships between verbal memory, demographics variables, and neuropsychological factors were established, and a hierarchical regression analysis was conducted to examine the individual contributions of these variables in predicting memory performance. Results: Bivariate correlations suggested that memory was significantly related to demographic factors, IQ, executive functioning, and semantic clustering. Importantly, hierarchical regression analysis revealed that semantic clustering significantly and independently contributed to recall performance beyond the demonstrated impacts of FSIQ, speed, executive functioning, and demographic variables. Furthermore, FSIQ did not moderate the relationship between semantic clustering and memory indicating that this strategy is an important factor in bolstering recall, independent of FSIQ. Conclusions: Our results highlight the critical importance of semantic clustering utilization in enhancing memory performance among healthy older adults.
N-terminal residues of human dyskerin are required for interactions with telomerase RNA that prevent RNA degradation

Abstract The telomerase holoenzyme responsible for maintaining telomeres in vertebrates requires many components in vivo, including dyskerin. Dyskerin binds and regulates the accumulation of the human telomerase RNA, hTR, as well as other non-coding RNAs that share the conserved H/ACA box motif. The precise mechanism by which dyskerin controls hTR levels is unknown, but is evidenced by defective hTR accumulation caused by substitutions in dyskerin, that are observed in the X-linked telomere biology disorder dyskeratosis congenita (X-DC). To understand the role of dyskerin in hTR accumulation, we analyzed X-DC substitutions K39E and K43E in the poorly characterized dyskerin N-terminus, and A353V within the canonical RNA binding domain (the PUA). These variants exhibited impaired binding to hTR and polyadenylated hTR species, while interactions with other H/ACA RNAs appear largely unperturbed by the N-terminal substitutions. hTR accumulation and telomerase activity defects of dyskerin-deficient cells were rescued by wildtype dyskerin but not the variants. hTR 3′ extended or polyadenylated species did not accumulate, suggesting hTR precursor degradation occurs upstream of mature complex assembly in the absence of dyskerin binding. Our findings demonstrate that the dyskerin-hTR interaction mediated by PUA and N-terminal residues of dyskerin is crucial to prevent unchecked hTR degradation.
Association of Occlusal Force with Cognition in Independent Older Japanese People

Recent longitudinal studies have shown the influence of multiple tooth loss on cognitive impairment, and earlier studies suggested that periodontal disease was related to cognitive decline. Tooth loss is associated with reduced masticatory function, which may affect stimulation of the central nervous system and dietary intake. Although some studies have reported a relationship between chewing ability and cognitive function, no studies have examined this area in terms of objective oral function. The aim of this study was to examine the association of occlusal force with cognitive decline in the preclinical stage among older people with higher-level functional capacity. This cross-sectional study for community-dwelling older people living in urban and rural areas in Japan examined 994 persons in the 70-y group (age range, 69–71 y) and 968 persons in the 80-y group (age range, 79–81 y). Retention of higher-level competence was defined according to the Tokyo Metropolitan Institute of Gerontology Index of Competence. Cognitive function was measured with the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Oral status and function were assessed by the number of remaining teeth, periodontal pocket depth, and maximal occlusal force. Associations between the MoCA-J score and occlusal force were examined by bivariate and multivariate analysis. Approximately one-half of the participants retained higher-level functional capacity and were included in the analysis. Multiple regression analysis showed that occlusal force was significantly related to cognitive function after controlling for possible predictors including age, sex, socioeconomic status, medical condition, and handgrip strength. The number of remaining teeth and periodontal pocket depth were not significantly associated with cognitive function. Among community-dwelling older people with retained competence, maximal occlusal force was positively associated with their cognitive function. These results suggest that oral function might be a predictor for preclinical cognitive decline. Knowledge Transfer Statement: Multiple regression analysis showed that occlusal force was significantly related to cognition after controlling for possible predictors including handgrip strength as an indicator of general muscle strength, suggesting the independence of oral function. The number of remaining teeth did not have this association. The majority of older people have lost teeth and have received prosthodontic treatment, and their occlusal force is determined not only by the number of remaining teeth but also by prosthetic rehabilitation. These results can be used by clinicians focusing on prevention of tooth loss among the entire population, as well as to encourage partially edentulous and fully edentulous patients to restore their oral function with prostheses in order to eliminate a possible risk factor for cognitive impairment.
Healthy Parks Healthy People as an Upstream Stress Reduction Strategy

Abstract:One of the primary goals of the Healthy Parks Healthy People (HPHP) program, located in the San Francisco Bay Area, is to offer group-based physical activities in natural settings. These activities are for racially and ethnically diverse groups of individuals as an “upstream” strategy for improving health. This study investigated the health impact of selected two-hour HPHP Bay Area events that targeted low-income racial and ethnic minority groups using physiological and self-reported measures of stress and related variables.Study participants (N = 52) in the selected HPHP Bay Area events donated saliva and filled out psychological measures of perceived stress (PSS-4; Cohen et al.) and mood state (I-PANAS-SF; Thompson, 2007) at the beginning and the end of a two-hour guided walk in green spaces. Moreover, a measure of perceived restoration (SRRS; Han, 2007) was completed at the end of the walk. Study participants wore a physical activity self-monitoring device (Garmin Vivofit 2) to capture their step count and heart rate during the event.Stress, both measured by the analysis of salivary cortisol and self-reported perceived stress, significantly decreased over the course of the event (p<.05) and there was a significant increase in positive mood (p<.05). The monitoring device also indicated that individuals were engaged in moderate levels of physical activity during the guided walks (x̄=8,990 steps, HR 95 bpm). The results encourage further development of nature-based health interventions to mitigate stress. Such interventions may be especially appropriate for low-income, urban, racial and ethnic minority groups that likely experience increased levels of stress due to social inequities and poor living conditions.
Examining the Efficacy of Targeted Component Interventions on Language and Literacy for Third and Fourth Graders Who are at Risk of Comprehension Difficulties

ABSTRACT Testing a component model of reading comprehension in a randomized controlled trial, we evaluated the efficacy of 4 interventions that were designed to target components of language and metacognition that predict children’s reading comprehension: vocabulary, listening comprehension, comprehension of literate language, academic knowledge, and comprehension monitoring. Third- and 4th-graders with language skills falling below age expectations participated (N = 645). Overall, the component interventions were only somewhat effective in improving the targeted skills, compared to a business-as-usual control (g ranged from −.14 to .33), and no main effects were significant after correcting for multiple comparisons. Effects did not generalize to other language skills or to students’ reading comprehension. Moreover, there were Child Characteristic × Treatment interaction effects. For example, the intervention designed to build sensorimotor mental representations was more effective for children with weaker vocabulary skills. Implications for component models of reading and interventions for children at risk of reading comprehension difficulties are discussed.
The association between religiosity and pregnancy acceptability among Latino/a young adults: does generational status matter?

Abstract The US Latino/a population is considered to be at high risk for unintended pregnancy; some research indicates that Latino/a parents are more likely to express happiness about an unintended pregnancy than other racial/ethnic groups. Associations between pregnancy attitudes and factors such as religiosity and nativity have also been documented in the Latino/a population, but existing research is sparse, dated and primarily focused on women of Mexican heritage. This study sought to expand this literature by examining the relationship between religiosity and pregnancy acceptability and assessing effect modification by generational status and gender in a national sample of young Latino/a cisgender women and men of various ancestral backgrounds currently in relationships. In multivariable logistic regression models, there was a positive association between importance of religion and pregnancy acceptability for both men and women; being highly or moderately religious was associated with elevated odds of finding a pregnancy acceptable. Effect modification by generational status was significant for women, but not for men. Results suggest that religiosity, gender and generational status have differential influences on and relationships to pregnancy orientations for Latina women and Latino men and should be considered in the design and delivery of family planning care for Latino/a clients.
Multiplexed and tunable transcriptional activation by promoter insertion using nuclease-assisted vector integration

Abstract The ability to selectively regulate expression of any target gene within a genome provides a means to address a variety of diseases and disorders. While artificial transcription factors are emerging as powerful tools for gene activation within a natural chromosomal context, current generations often exhibit relatively weak, variable, or unpredictable activity across targets. To address these limitations, we developed a novel system for gene activation, which bypasses native promoters to achieve unprecedented levels of transcriptional upregulation by integrating synthetic promoters at target sites. This gene activation system is multiplexable and easily tuned for precise control of expression levels. Importantly, since promoter vector integration requires just one variable sgRNA to target each gene of interest, this procedure can be implemented with minimal cloning. Collectively, these results demonstrate a novel system for gene activation with wide adaptability for studies of transcriptional regulation and cell line engineering.
Pelvic Organ Segmentation with Sample Attention based Stochastic Connection Networks.

Synopsis: Accurate segmentation of pelvic organs is important for prostate radiation therapy. Modern radiation therapy starts to use magnetic resonance image (MRI) as an alternative to CT image because of the superior soft tissue contrast of MRI and also no risk of radiation exposure. In this paper, we propose a novel deep network architecture, called “Sample Attention based Stochastic Connection Networks” (SASCNet), to delineate pelvic organs from MRI in an end-to-end fashion. Our proposed network has two main contributions: 1) We propose a novel randomized connection module and adopt it as a basic unit to combine the shallower and deeper layers in the fully convolutional networks (FCN); 2) We propose a novel adversarial attention mechanism to automatically dispatch sample importance so that we can avoid easy sample’s domination over training the network. Experimental results show that our SASCNet achieved competitive segmentation accuracy.