Miracle-dz/UniFAR-FTUs huggingface dataset:
Patient Engagement With an Automated Telephone Symptom Management Intervention: Predictors and Outcomes.

BACKGROUND Self-management of symptoms related to cancer and its treatment is important for maintaining treatment regimens and improving outcomes. PURPOSE To determine factors associated with engagement in a symptom self-management intervention among patients initiating oral anticancer treatment. METHODS This secondary analysis included 127 patients randomized to the medication adherence reminder and symptom management intervention in a recently completed trial. Patients were recruited from six Comprehensive Cancer Centers, interviewed at intake, and mailed a Symptom Management Toolkit (Toolkit) with self-care management strategies for 18 symptoms. During eight automated telephone weekly calls, patients were asked to use the Toolkit to manage elevated symptoms. Toolkit use and symptoms were tracked weekly, and generalized linear mixed-effects models were used to determine factors predictive of Toolkit use. General linear modeling was used to relate the Toolkit use during intervention to postintervention symptom severity. RESULTS Better cognitive function at intake into the trial and higher symptom burden were predictive of the patients' initial decision to try the Toolkit during Week 1. In subsequent weeks, Toolkit use in the previous week and worsening of symptoms were associated with greater odds of Toolkit use. The extent of Toolkit use modified the relationship between intake and 8 week symptom severity: among patients with higher levels of severity at intake, use of the Toolkit conferred greater benefit at 8 weeks. CONCLUSIONS Patients make realistic decisions regarding when to use a self-directed approach to self-management and are likely to use strategies when their symptoms are higher and to forego use once symptoms subside. CLINICAL TRIAL REGISTRATION NCT02043184.
A Meta-Analysis Assessing the Association Between COL11A1 and GDF5 Genetic Variants and Intervertebral Disc Degeneration Susceptibility.

STUDY DESIGN Meta-analysis to collect relevant studies to assess the association between COL11A1 and GDF5 genetic variants and susceptibility to IDD. OBJECTIVE To assess whether or not COL11A1 and GDF5 genetic variants were associated with susceptibility to IDD. SUMMARY OF BACKGROUND DATA IDD or LDH is a major public health problem. There have been several studies evaluating the relationship between COL11A1 and GDF5 genetic variants with risk of IDD. However, the studies were limited in discrete outcome and sample size, and some of the results were contradictory. METHODS We systematically searched the relevant publications in electronic databases. Eligible studies were included based on the defined criteria. The pooled ORs with its 95% CIs were received using STATA 15. Subgroup analysis, sensitivity analysis, publication bias and the "Trim and fill" method were performed in the meta-analysis. RESULTS A total of 3287 IDD cases and 5115 controls were incorporated into the meta-analysis. Our results demonstrated that COL11A1 rs1676486 was significantly associated with increased IDD susceptibility under all genetic models (allele model T vs C: OR = 1.40, 95% CI 1.23-1.59, P = 0.000; homozygote model TT vs CC: OR = 1.89, 95%CI 1.40-2.56, P = 0.000; dominant model TT+TC vs CC: OR = 1.52, 95%CI 1.29-1.80, P = 0.000; recessive model TT vs TC+CC: OR = 1.58, 95%CI 1.18-2.12, P = 0.002). However, GDF5 rs143383 was not (allele model T vs C: OR = 1.15, 95%CI 0.91-1.44, P = 0.244; homozygote model TT vs CC: OR = 1.22, 95%CI 0.75-2.00, P = 0.429; dominant model TT vs CC+CT: OR = 1.22, 95%CI 0.95-1.57, P = 0.112; recessive model TC+TT vs CC: OR = 1.12, 95%CI 0.73-1.73, P = 0.594). Subgroup analysis indicated ethnicity was not the source of heterogeneity. Sensitivity analysis, publication bias and the "Trim and fill" method demonstrated the meta-analysis was of reliability. CONCLUSIONS Our results suggested that COL11A1 rs1676486 was significantly associated with IDD and the T allele was a risky factor. However, GDF5 rs143383 was not. LEVEL OF EVIDENCE 1.
Oral misoprostol, low dose vaginal misoprostol, and vaginal dinoprostone for labor induction: Randomized controlled trial

Objective To compare effectiveness and safety of oral misoprostol (50 μg every four hours as needed), low dose vaginal misoprostol (25 to 50 μg every six hours as needed), and our established dinoprostone vaginal gel (one to two mg every six hours as needed) induction. Materials and methods Consenting women with a live term single cephalic fetus for indicated labor induction were randomized (3N = 511). Prior uterine surgery or non-reassuring fetal surveillance were exclusions. Concealed computer generated randomization was stratified and blocked. Newborns were assessed by a team unaware of group assignment. The primary outcome was time from induction at randomization to vaginal birth for initial parametric analysis. Sample size was based on mean difference of 240 minutes with α2 = 0.05 and power 95%. Non-parametric analysis was also pre-specified ranking cesareans as longest vaginal births. Results Enrollment was from April 1999 to December 2000. Demographics were similar across groups. Analysis was by intent to treat, with no loss to follow up. Mean time (±SD) to vaginal birth was 1356 (±1033) minutes for oral misoprostol, 1530 (±3249) minutes for vaginal misoprostol, and 1208 (±613) minutes for vaginal dinoprostone (P = 0.46, ANOVA). Median times to vaginal birth were 1571, 1339, and 1451 minutes respectively (P = 0.46, Kruskal-Wallis). Vaginal births occurred within 24 hours in 44.9, 53.5 and 47.7% respectively (P = 0.27, χ2). There were no significant differences in Kaplan Meier survival analyses, cesareans, adverse effects, or maternal satisfaction. The newborn who met birth asphyxia criteria received vaginal misoprostol, as did. all three other newborns with cord artery pH<7.0 (P = 0.04, Fisher Exact). Conclusion There was no significant difference in effectiveness of the three groups. Profound newborn acidemia, though infrequent, occurred only with low dose vaginal misoprostol.
Low-dose/low-dose-rate radiation: a feasible strategy to improve cancer radiotherapy?

Abbreviations: atomic bomb, (A-bomb); Central nervous system, (CNS); chronic myelogenous leukemia, (CML); computed tomography, (CT); different poly(ADP-ribose) polymerase-1, (PARP-1); epidermal growth factor receptors, (EGFR); Epstein-Barr virus, (EBV); Food and Drug Administration, (FDA); gastrointestinal tract, (GI); human lung fibroblasts, (HFL-1); hypoxanthine-guanine phosphoribosyl transferase, (HPRT); Lewis lung carcinoma, (LLC); intensity-modulated radiation therapy, (IMRT); linear energy transfer, (LET); lipopolysaccharide, (LPS); magnetic resonance imaging, (MRI); major histocompatibility complex, (MHC); monoclonal antibodies, (Mab); Natural killer, (NK); positron emission tomography, (PET); retinoblastoma, (Rb); subcutaneous, (s.c.); T cytotoxic, (Tc); T helper, (Th); thymidine kinase, (tk); total-body irradiation, (TBI); vascular endothelial growth factor, (VEGF)
Recovery of health-related quality of life after burn injuries: An individual participant data meta-analysis

Background A prominent outcome measure within burn care is health related quality of life (HRQL). Until now, no model for long-term recovery of HRQL exists for adult burn patients which requires large samples with repeated measurements. Re-use and the combination of existing data is a way to achieve larger data samples that enable the estimation of long-term recovery models. The aim of this secondary data analysis was to assess the recovery of HRQL after a burn injury over time. Methods and findings Data from ten European studies on generic HRQL assessed in adult burn patients (either with the EQ-5D or SF-36) from five different countries were merged into one dataset. SF-36 outcomes were transformed into EQ-5D outcomes. A 24-month recovery of HRQL (EQ-5D utility) was modeled using a linear mixed-effects model and adjusted for important patient and burn characteristics. Subgroups of patients with mild and intermediate burns (≤20% total body surface area (TBSA) burned) and with major burns (>20% TBSA burned) were compared. The combined database included 1687 patients with a mean age of 43 (SD 15) years and a median %TBSA burned of 9% (IQR 4–18). There was large improvement in HRQL up to six months after burns, and HRQL remained relatively stable afterwards (studied up to 24 months post burn). However, the estimated EQ-5D utility scores remained below the norm scores of the general population. In this large sample, females, patients with a long hospital stay and patients with major burns had a delayed and worse recovery. The proportion of patients that reported problems for the EQ-5D dimensions ranged from 100% (pain/discomfort at baseline in patients with major burns) to 10% (self-care ≥3 months after injury in patients with mild and intermediate burns). After 24 months, both subgroups of burn patients did not reach the level of the general population in the dimensions pain/discomfort and anxiety/depression, and patients with major burns in the dimension usual activities. A main limitation of the study includes that the variables in the model were limited to age, gender, %TBSA, LOS and time since burn as these were the only variables available in all datasets. Conclusions The 24-month recovery model can be used in clinical practice to inform patients on expected HRQL outcomes and provide clinicians insights into the expected recovery of HRQL. In this way, a delayed recovery can be recognized in an early stage and timely interventions can be started in order to improve patient outcomes. However, external validation of the developed model is needed before implementation into clinical practice. Furthermore, our study showed the benefit of secondary data usage within the field of burns.
Diagnostic performance of whole-lesion apparent diffusion coefficient histogram analysis metrics for differentiating benign and malignant breast lesions: a systematic review and diagnostic meta-analysis

Background Although whole-lesion apparent diffusion coefficient (ADC) histogram has been increasingly used for breast lesions, it has not been routinely used in clinical practice as an emergent promising imaging tool. Purpose To evaluate the performance of whole-lesion ADC histogram analysis metrics for differentiating benign and malignant breast lesions. Material and Methods A systematic PubMed/EMBASE/Cochrane electronic database search was performed for original diagnostic studies from 1 January 1970 to 2 January 2019. Summary estimates of diagnostic accuracy were generated and meta-regression was performed to explore sources of heterogeneity according to study and magnetic resonance imaging characteristics. Results Five original articles involving 493 patients were included in the meta-analysis. The pooled sensitivity and specificity of whole-lesion ADC histogram analysis were 0.85 (95% confidence interval [CI] = 0.81–0.89) and 0.79 (95% CI = 0.72–0.84) for distinguishing benign and malignant breast lesions, respectively. The area under the curve (AUC) was 0.9178. No publication bias was detected (P = 0.51). In subgroup analysis, the summary sensitivity and specificity of 50th percentile ADC value were 0.81 (95% CI = 0.71–0.88) and 0.86 (95% CI = 0.74–0.94), respectively. Meta-regression analysis indicated no covariates were sources of heterogeneity (P > 0.05). Conclusion Whole-lesion ADC histogram analysis demonstrated good diagnostic performance for differentiating between benign and malignant breast lesions, with 50th percentile ADC value showing higher diagnostic accuracy than other histogram parameters. Given the limited number of studies included in the analysis, the findings from our meta-analysis will need further confirmation in future research.
Can Differences in Early Hearing Development Be Distinguished by the LittlEARs Auditory Questionnaire?

Objective: This study asks whether the LittlEARs Auditory Questionnaire (LEAQ), a caregiver measure, can differentiate between the early auditory development of children with bilateral cochlear implants (CIs), bilateral hearing aids (HAs), and children with Auditory Neuropathy Spectrum Disorder (ANSD) who wear CIs or HAs. The LEAQ is sensitive to impaired auditory development but has not previously been used to distinguish developmental changes between groups of children using different hearing technologies or with different types of hearing loss. Design: We collected retrospective longitudinal LEAQ results from 43 children with HAs, 43 with CIs, and 18 with ANSD. The children with ANSD wore hearing technology. They were a similar age to the children without ANSD (23 months; SD = 15), while the CI group (14 months; SD = 8) was younger than the HA group (24 months; SD = 18) [F(2,98.48) = 3.4; p = 0.04]. The CI group often participated in their first LEAQ pretreatment. Participants completed between one and seven LEAQs. Scores ranged between zero and 35 (mean = 18.36). We conducted a linear mixed-effects analysis, which included age or time since device fitting, hearing type (HA, CI, or ANSD), and presence of a comorbidity as fixed effects. A secondary analysis assessed effects of device audibility, measured by the Speech Intelligibility Index or Articulation Index, and consistency of device use obtained from device datalogs. Results: Children with CIs progressed faster than their peers with HAs or ANSD [χ2(8) = 24.51; p = 0.002]. However, within a subsample that included consistency of device use (β7 = −0.20 ± 0.38, t = −0.52; β8 = 0.93 ± 0.82, t = 1.13) and audibility (β6 = −0.70 ± 1.45, t = −1.87; β7 = 0.87 ± 0.89, t = 0.98), study group did not significantly influence rate of improvement on the LEAQ. In addition, children with developmental delays in all three study groups demonstrated significantly slower LEAQ score improvement [χ2(6) = 23.60; p < 0.001] and a trend toward decreased consistency of device use [F(1) = 3.31; p = 0.07]. As we expected, children in the CI and HA groups were more likely to achieve auditory skills indicated in early rather than later LEAQ questions. There was less variability in the responses of the ANSD group [CI: interquartile range (IQR) = 9; HA: IQR = 8; ANSD: IQR = 1]. There was no connection between LEAQ growth and speech perception outcomes in a subsample [r(6) = 0.42; p = 0.30]. Conclusions: The LEAQ is a useful tool for monitoring initial auditory development in very young children and can inform early treatment decisions.
Epigenetic factor siRNA screen during primary KSHV infection identifies novel host restriction factors for the lytic cycle of KSHV

Establishment of viral latency is not only essential for lifelong Kaposi’s sarcoma-associated herpesvirus (KSHV) infection, but it is also a prerequisite of viral tumorigenesis. The latent viral DNA has a complex chromatin structure, which is established in a stepwise manner regulated by host epigenetic factors during de novo infection. However, despite the importance of viral latency in KSHV pathogenesis, we still have limited information about the repertoire of epigenetic factors that are critical for the establishment and maintenance of KSHV latency. Therefore, the goal of this study was to identify host epigenetic factors that suppress lytic KSHV genes during primary viral infection, which would indicate their role in latency establishment. We performed an siRNA screen targeting 392 host epigenetic factors during primary infection and analyzed which ones affect the expression of the viral replication and transcription activator (RTA) and/or the latency-associated nuclear antigen (LANA), which are viral genes essential for lytic replication and latency, respectively. As a result, we identified the Nucleosome Remodeling and Deacetylase (NuRD) complex, Tip60 and Tip60-associated co-repressors, and the histone demethylase KDM2B as repressors of KSHV lytic genes during both de novo infection and the maintenance of viral latency. Furthermore, we showed that KDM2B rapidly binds to the incoming viral DNA as early as 8 hpi, and can limit the enrichment of activating histone marks on the RTA promoter favoring the downregulation of RTA expression even prior to the polycomb proteins-regulated heterochromatin establishment on the viral genome. Strikingly, KDM2B can also suppress viral gene expression and replication during lytic infection of primary gingival epithelial cells, revealing that KDM2B can act as a host restriction factor of the lytic cycle of KSHV during both latent and lytic infections in multiple different cell types.
Theoretical study of oxygen insertion and diffusivity in the g-TiAl L10 system

This work is a first-principles study of the insertion and diffusivity of oxygen in the -TiAl L10 system. Five interstitial positions were identified as stable. One, however, the 2h site a pyramid composed of a Ti square topped by an Al atom, was found more stable than the others. The oxygen interactions with the TiAl system were thus studied and analyzed in detail using vibrational, elastic and electronic properties. The results show that the O atom prefers to be surrounded by Ti atoms and tries to minimize the number of bonds with aluminum. The diffusion mechanism is subsequently studied at the atomic scale, by analyzing displacements between stable interstitial sites. The oxygen diffusivity is found to be anisotropic and the components in the x and z direction, Dx and Dz, are then calculated and compared with those of O diffusion into other Ti–Al alloys. The analysis of results shows two effects. First, the stability of sites is related to the number of O–Al bonds, the fewer there are, the more stable the site is, and second, the diffusion is faster when the content of interstitial sites composed of many Ti atoms is low.
Identification and Evaluation of Reference Genes for Normalization of Gene Expression in Developmental Stages, Sexes, and Tissues of Diaphania caesalis (Lepidoptera, Pyralidae)

Abstract Diaphania caesalis (Walker) is an important boring insect mainly distributed in subtropical and tropical areas and attacked tropical woody grain crops, such as starchy plants of Artocarpus. Quantitative real-time polymerase chain reaction (qRT-PCR) is a powerful approach for investigating target genes expression profiles at the transcriptional level. However, the identification and selection of internal reference genes, which is often overlooked, is the most vital step before the analysis of target gene expression by qRT-PCR. So far, the reliable internal reference genes under a certain condition of D. caesalis have not been investigated. Therefore, this study evaluated the expression stability of eight candidate reference genes including ACT, β-TUB, GAPDH, G6PDH, RPS3a, RPL13a, EF1α, and EIF4A in different developmental stages, tissues and sexes using geNorm, NormFinder and BestKeeper algorithms. To verify the stability of the recommended internal reference genes, the expression levels of DcaeOBP5 were analyzed under different treatment conditions. The results indicated that ACT, RPL13a, β-TUB, RPS3a, and EF1α were identified as the most stable reference genes for further studies on target gene expression involving different developmental stages of D. caesalis. And ACT and EIF4A were recommended as stable reference genes for different tissues. Furthermore, ACT, EF1α, and RPS3a were ranked as the best reference genes in different sexes based on three algorithms. Our research represents the critical first step to normalize qRT-PCR data and ensure the accuracy of expression of target genes involved in phylogenetic and physiological mechanism at the transcriptional level in D. caesalia.
Association between polygenic liability for schizophrenia and substance involvement: A nationwide population‐based study in Taiwan

Schizophrenia and substance involvement frequently co‐occur in individuals, and a bidirectional relationship between the two has been proposed; shared underlying genetic factors could be an alternative explanation. This study investigated the genetic overlap between schizophrenia and substance involvement, including tobacco, alcohol and betel nut use. The study subjects were recruited from the Taiwan Biobank, and genome‐wide genotyping data was available for 18 327 participants without schizophrenia. We calculated the Psychiatric Genomics Consortium‐derived polygenic risk score (PRS) for schizophrenia in each participant. The significance of the schizophrenia PRS associated with substance involvement was evaluated using a regression model with adjustments for gender, age and population stratification components. The modified effect of gender or birth decade was also explored. The schizophrenia PRS was positively associated with lifetime tobacco smoking in women (OR in per SD increase in PRS = 1.12 with 95% CI 1.04‐1.20, P = .002), but not in men (OR = 0.99 with 95% CI 0.95‐1.04, P = .74), and the gender‐PRS interaction reached significance (P = .006). The OR between PRS and lifetime tobacco smoking increased with the birth decade (P of birth decade‐PRS interaction = .0002). In women, OR increased from 0.97 (P = .85) for subjects with a birth decade before 1950 to 1.21 (P = .04) for subjects with a birth decade after 1980; in men, the corresponding OR increased from 0.88 (P = .04) to 1.13 (P = .11). There was no association between schizophrenia PRS and alcohol/betel nut use phenotypes. This study provides evidence for the genetic overlap between schizophrenia and tobacco use in women, and this overlap was stronger in the younger population.
Designed Protein Cages as Scaffolds for Building Multi-Enzyme Materials.

The functions of enzymes can be strongly affected by their higher-order spatial arrangements. In this study we combine multiple new technologies - designer protein cages and sortase-based enzymatic attachments between proteins - as a novel platform for organizing multiple enzymes (of one or more types) in specified configurations. As a scaffold we employ a previously characterized 24-subunit designed protein cage whose termini are outwardly exposed for attachment. As a first-use case, we test the attachment of two cellulase enzymes known to act synergistically in cellulose degradation. We show that, after endowing the termini of the cage subunits with a short 'sort-tag' sequence (LPXTG) and the opposing termini of the cellulase enzymes with a short polyglycine sequence tag, addition of sortase covalently attaches the enzymes to the cage with good reactivity and high copy number. The doubly-modified cages show enhanced activity in a cellulose degradation assay compared to enzymes in solution, and compared to a combination of singly modified cages. These new engineering strategies could be broadly useful in the development of enzymatic material and synthetic biology applications.
How to Produce Methane Precursor in the Upper Ocean by An Untypical Non-heme Fe-dependent Methylphosphonate Synthase?

A new methane formation pathway, which uses methylphosphonate (MPn) as the methane precursor, has been discovered in the upper ocean. Methylphosphonate synthase (MPnS) is a key piece in this pathway to produce MPn from 2-hydroxyethylphosphonate (2-HEP), using an untypical 2-His-1-Gln non-heme iron architecture. Herein, the MPnS reaction mechanism was demonstrated by the density functional calculations to mainly include the substrate hydroxyl deprotonation, the formation of a MPn radical and a formate, and the hydrogen abstraction of formate by MPn radical. The second-shell Lys28' may serve as a proton reservoir activating 2-HEP and regenerating the Fe site. The Fe-bound superoxide radical is a bifunctional species to deprotonate the substrate hydroxyl and abstract the substrate methylene hydrogen. Several alternative mechanisms have been ruled out. Furthermore, the catalytic activity of MPnS was found to be inactivated/reduced by the mutation of Gln152E/Gln152H/Gln152D, rendering a significant evolutionary advantage with an uncommon 2-His-1-Gln triad introduced to the ferrous coordination sphere.