Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-Term Results and Reconstruction Failure in Patients Receiving Postmastectomy Radiation Therapy with a Temporary Expander or Permanent Implant in Place

Background: This study investigated the risk of reconstruction failure after mastectomy, immediate breast reconstruction, and radiotherapy to either a temporary tissue expander or permanent implant. Methods: Records of women treated at a single institution between June of 1997 and December of 2011 were reviewed. Two patient groups were identified based on type of immediate breast reconstruction: tissue expander followed by exchange with a permanent implant and permanent implant. The study endpoint was rate of reconstruction failure, defined as a replacement, loss of the implant, or conversion to flap. Results: The tissue expander/permanent implant and the permanent implant groups consisted of 63 and 75 patients, respectively. The groups were well balanced for clinical and treatment characteristics. With a median follow-up of 116 months, eight implant losses, 50 implant replacements, and four flap conversions were recorded. Reconstruction failure occurred in 22 of 63 patients in the expander/implant group and in 40 of 75 patients in the permanent implant group. A traditional proportional hazards model showed a higher risk of reconstruction failure for the expander/implant group (hazard ratio, 2.01) and a significantly shorter time to reconstruction failure compared with the permanent implant group (109.2 months versus 157.7 months; p = 0.03); however, according to a competing risk model, the between-groups cumulative incidences were not significantly different (hazard ratio, 1.09). Conclusions: Radiotherapy to either a tissue expander or a permanent implant presented a fairly large risk of reconstruction failure over time. The expander/implant group was not more likely to develop reconstruction failure compared to permanent implant group, but the timing of onset was shorter. More complex techniques should be investigated to lower the risk of reconstruction failure. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
FSH/AMH Ratio and Adipocyte Size are Linked to Ovarian Dysfunction

ABSTRACT Background and Aim While the relationship between obesity and reproductive dysfunction is well known, the physiological mechanism behind obesity-related infertility remains unclear. Previous work suggests that follicle development prior to ovulation is disrupted in obese individuals. Follicle-stimulating hormone (FSH) and anti-Mullerian hormone (AMH) are two key regulators of follicle development, and the poorest reproductive outcomes have been recorded when these hormones are imbalanced. In order to understand how obesity impacts the reproductive axis, the present study induces reproductive dysfunction in female rats using a high-fat, high-sugar diet (HFHS). Results: In our study, several animals on the HFHS diet displayed abnormal estrous cycles. The HFHS diet also resulted in an increased prevalence of ovarian cysts and decreased formation of corpora lutea. Across all groups, the FSH/AMH ratio displayed a strong negative correlation with pre-antral, antral, and total follicle counts. Moreover, rats on the HFHS diet displayed larger adipocytes and produced higher levels of leptin than controls. When combined with average adipocyte size in multiple regression, the FSH/AMH ratio was strongly associated with cyst formation in the ovary. Conclusions: These findings provide strong evidence for the potential relevance of a combined FSH/AMH ratio as a marker of ovarian health and follicular status. Therefore, this ratio reflects a complex interaction between the reproductive and metabolic systems.
Uncovering, creating or constructing problems? Enacting a new role to support staff who raise concerns about quality and safety in the English National Health Service

Employee voice is an important source of organizational intelligence about possible problems in quality and patient safety, but effective systems for encouraging and supporting those who seek to speak up have remained elusive. In the English National Health Service, a novel role known as the ‘Freedom to Speak Up Guardian’ has been introduced to address this problem. We critically examine the role and its realization in practice, drawing on semi-structured interviews with 51 key individuals, including Guardians, clinicians, managers, policymakers, regulators and others. Operationalizing the new role in organizations was not straightforward, since it had to sit in a complex set of existing systems and processes. One response was to seek to bound the scope of Guardians, casting them in a signposting or coordinating role in relation to quality and safety concerns. However, the role proved hard to delimit, not least because the concerns most frequently voiced in practice differed in character from those anticipated in the role’s development. Guardians were tasked with making sense of and dealing with issues that could not always straightforwardly be classified, deflected to the right system or escalated to the appropriate authority. Our analysis suggests that the role’s potential contribution might be understood less as supporting whistleblowers who bear witness to clear-cut wrongdoing, and more as helping those with lower-level worries to construct their concerns and what to do with them. These findings have implications for how voice is understood, imagined and addressed in healthcare organizations.
beta-Hydroxysteroid dehydrogenase type 12 is responsible for maturation-inducing steroid synthesis during oocyte maturation in Nile tilapia

8 17α, 20β -Dihydroxy-4-pregnen-3-one (DHP) is a maturation-inducing steroid in many teleost 9 fish. Carbonyl reductase-like 20β -hydro xysteroid dehydrogenase (CR/20β -HSD) is a 10 candidate enzyme responsible for DHP production during oocyte maturation in various fish, 11 including Nile tilapia. However, a novel type of 17β -hydroxysteroid dehydrogenase, type 12-12 like ( 17β -HSD12L), is responsible for DHP production during oocyte maturation in masu 13 salmon. 17β - HSD12 (presumably orthologous to salmon 17β -HSD12L) has been detected in 14 Nile tilapia; however, its enzymatic activity and specific ability to convert the DHP substrate 15 17α -hydroxyprogesterone (17OHP) have not been examined. This study aimed to determine 16 whether CR/20β - HSD or 17β -HSD12 is responsible for DHP production during oocyte 17 maturation in the Nile tilapia. Mammalian expression vectors containing tilapia hsd17b12 or 18 CR/20bhsd were transfected into HEK293T cells, followed by incubation with 17OHP. 19 HEK293T cells transfected with hsd17b12 exhibited a strong ability to convert exogenous 20 17OHP to DHP (73.8% yield). Cells transfected with CR/20bhsd or the control vector 21 converted only 7.4% and 7.5% of 17OHP to DHP, respectively. In addition, based on LC-22 MS/MS analyses , 17β -HSD12 did not convert any substrates other than 17OHP, including 23 DHP, adrenosterone, androstenedione, estrone, testosterone, 11-ketotestosterone, and 24 estradiol-17 β . CR/20β -HSD showed strong 17β -HSD oxidoreductase activity especially with 25 adrenosterone and androstenedione. Tissue-specific hsd17b12 expression analyzed by RT-26 PCR showed that hsd17b12 mRNA was strongest amplification in full-grown follicles. 27 Finally, full-grown ovarian follicles were incubated with salmon pituitary extract (SPE, 100 28 µg/mL) or human chorionic gonadotropin (HCG, 100 IU/mL) to induce 20β -HSD activity in 29 vitro , and enzyme activity was assessed by co-incubation with 100 ng/mL 17OHP for 2, 4, 8, 30 and 16 h. Conversion of 17OHP to DHP by ovarian follicles incubated with SPE and HCG 31 peaked at 16 h, subsequent with increased follicular hsd17b12 mRNA levels, which were 32 significantly higher than those in control incubations. However, the levels of CR/20bhsd 33 mRNA remained low and did not differ among time points. The present study strongly 34 suggests that 17β - HSD12, and not CR/20β - HSD, is the 20β -HSD responsible for DHP 35 production by ovarian follicles during oocyte maturation in Nile tilapia. 36
Volatile Essential Oils Can Be Used to Improve the Efficacy of Heat Treatments Targeting the Western Drywood Termite: Evidence from a Laboratory Study

Abstract Use of heated air to create lethal temperatures within infested wood serves as a nonchemical treatment option against western drywood termites, Incisitermes minor (Hagen). When treating a whole or large portion of the structure, however, the presence of hard-to-heat areas (structural heat sinks) and potential risk of damaging heat-sensitive items are recognized as important challenges. To address these challenges, we tested if the incorporation of a volatile essential oil would increase the overall efficacy of heat treatments against the drywood termites. To choose an essential oil for use, we tested the volatile action of several candidate compounds against individual termites using a fumigant toxicity assay. As a proof-of-concept experiment, field-collected termites were housed in small wooden arenas and subsequently subjected to 2-h heat treatment at various air temperatures within a gas chromatography oven. A simulated heat sink and essential oil treatment was also included in the experimental design. Analyses of lethal temperatures (LTemp50 and LTemp99 values), probabilities of mortality, and survivorship data over time suggested that 1) the presence of a heat sink significantly increased the minimum air temperature needed for complete kill of the termites and 2) the volatile essential oil added at the site of a heat sink effectively counteracted the impact of the heat sink. The use of volatile essential oils makes it possible to effectively kill drywood termites even in areas which might not reach lethal temperatures (∼50°C), potentially improving the overall efficacy of heat treatments while reducing the risk of heat damage.
Microarray Analysis of Differential Gene Expression in Alzheimer’s Disease Identifies Potential Biomarkers with Diagnostic Value

Background Alzheimer disease (AD) is a common and fatal subtype of dementia that remains a challenge to diagnose and treat. This study aimed to identify potential biomarkers that influence the prognosis of AD. Material/Methods A total of 6 gene expression profiles from the Gene Expression Omnibus (GEO) database were assessed for their potential as AD biomarkers. We identified differentially expressed genes (DEGs) using the prediction analysis for microarray (PAM) algorithm and obtained hub genes through the analysis of the protein-protein interaction (PPI) network and module analysis. Results We identified 6 gene expression profiles from the GEO database and assessed their potential as AD biomarkers. Shared gene sets were extracted and integrated into large expression profile matrices. We identified 2514 DEGs including 68 upregulated- and 2446 downregulated genes through analysis of the limma package. We screened 379 significant DEGs including 68 upregulated and 307 downregulated genes for their ability to distinguish AD from control samples using PAM algorithm. Functional enrichment of the 379 target genes was produced from Database for Annotation, Visualization and Integrated Discovery. (DAVID) and included histone function, beta receptor signaling, cell growth, and angiogenesis. The downregulated genes were significantly enriched in MAPK signaling, synaptic signaling, neuronal apoptosis and AD associated pathways. Upon analysis of the PPI network, 32 hub genes including ENO2, CCT2, CALM2, ACACB, ATP5B, MDH1, and PP2CA were screened. Of these hub genes, NFKBIA and ACACB were upregulated and 29 genes were downregulated in AD patients. Conclusions We screened 379 significant DEGs as potential biomarkers of AD using PAM and obtained 32 hub genes through PPI network and module analysis. These findings reveal new potential AD biomarkers with prognostic and therapeutic value.
Changes in Health-Related Quality of Life for Older Persons With Cognitive Impairment After Hip Fracture Surgery: A Systematic Review

ABSTRACT Background Hip fractures in persons with cognitive impairments represent a major public health issue in older populations that often results in poor health-related quality of life (HRQoL). Purpose The aim of this systemic review was to examine the changes in HRQoL in older, cognitively impaired patients with hip fracture who had received surgical treatment. Methods A literature search of PubMed, Scopus, MEDLINE, PsycINFO, and CINAHL (EBSCO) databases was conducted for studies published up to July 2018 that addressed the issue of HRQoL in cognitively impaired patients with hip fracture after surgery. Studies that met the following criteria were included: Patients with hip fracture were over 60 years old and had cognitive impairment or dementia, patients had undergone hip fracture repair surgery, HRQoL was determined using standardized questionnaires, a descriptive or interventional methodology was used, and the full-text article was available in English. Results A primary search of databases yielded 1,528 studies, 621 duplicates were removed, and the remaining 907 abstracts were screened. Thirty-four full-text articles were deemed relevant for full review; of these, 10 articles met the criteria for inclusion in the review. Cognitive impairment was found to impact negatively on the patients' HRQoL after hip fracture surgery (n = 809). Severity of cognitive impairment was correlated with deterioration in HRQoL after hospital discharge. When compared with prefracture measures of HRQoL, the greatest deterioration in HRQoL postsurgery occurred during the first 4 months after discharge. Impacts on HRQoL for patients with cognitive impairment at later time points differed depending on type of hip fracture and type of surgical treatment. However, for most of the patients, HRQoL remained relatively unchanged at 6, 12, and 24 months postdischarge. Conclusions We recommend nursing care interventions for older persons with cognitive impairment be initiated immediately after surgery for hip fracture to prevent a significant decline in HRQoL. Further examination of interventions that are effective in maintaining HRQoL for these patients such as interdisciplinary care is necessary. In addition, the influences of hip fracture type and surgical approach on changes in HRQoL suggest a need for further investigations to determine what contributed to the observed inconsistencies in the outcomes.
Toward a better understanding of metabolic and pharmacokinetic characteristics of low-solubility, low-permeability natural medicines

Abstract Today, it is very challenging to develop new active pharmaceutical ingredients. Developing good preparations of well-recognized natural medicines is certainly a practical and economic strategy. Low-solubility, low-permeability natural medicines (LLNMs) possess valuable advantages such as effectiveness, relative low cost and low toxicity, which is shown by the presence of popular products on the market. Understanding the in vivo metabolic and pharmacokinetic characteristics of LLNMs contributes to overcoming their associated problems, such as low absorption and low bioavailability. In this review, the structure-based metabolic reactions of LLNMs and related enzymatic systems, cellular and bodily pharmacological effects and metabolic influences, drug–drug interactions involved in metabolism and microenvironmental changes, and pharmacokinetics and dose-dependent/linear pharmacokinetic models are comprehensively evaluated. This review suggests that better pharmacological activity and pharmacokinetic behaviors may be achieved by modifying the metabolism through using nanotechnology and nanosystem in combination with the suitable administration route and dosage. It is noteworthy that novel nanosystems, such as triggered-release liposomes, nucleic acid polymer nanosystems and PEGylated dendrimers, in addition to prodrug and intestinal penetration enhancer, demonstrate encouraging performance. Insights into the metabolic and pharmacokinetic characteristics of LLNMs may help pharmacists to identify new LLNM formulations with high bioavailability and amazing efficacy and help physicians carry out LLNM-based precision medicine and individualized therapies. Graphical Abstract
Psychopathy and Aggression: The Role of Emotion Dysregulation

The importance of psychopathy in the forensic and criminal justice domains is largely due to its robust associations with aggression and violent behavior. Hence, investigators have increasingly been interested in elucidating potential mechanisms linking psychopathy and aggression. Recent research highlighted previously overlooked associations between psychopathy and difficulties in emotion regulation, the process responsible for monitoring, evaluating, and managing one’s emotional experience, as well as for guiding behavior under intense emotional arousal. Yet, it remains unclear whether emotion dysregulation may be helpful to explain well-documented associations between psychopathy and aggression. The present study examined whether emotion dysregulation mediated associations (i.e., explained a significant portion of the shared variance) between psychopathy and aggression across community (N = 521) and offender (N = 268) samples. Participants completed self-report measures of psychopathy, emotion dysregulation, trait aggressiveness (i.e., anger, hostility, physical and verbal aggression), as well as reactive and proactive aggression. Across both samples, psychopathy had significant indirect effect on all indices of aggression through emotion dysregulation, with the exception of verbal aggression. These findings support the relevance of emotion regulation for the construct of psychopathy and its maladaptive correlates and highlight the potential relevance of focusing on emotion regulation as a possible target for interventions aimed at reducing aggression among individuals with psychopathic traits.
Benchmark Dose Analysis of DNA Damage Biomarker Responses Provides Compound Potency and Adverse Outcome Pathway Information for the Topoisomerase II Inhibitor Class of Compounds

Genetic toxicology data have traditionally been utilized for hazard identification to provide a binary call for a compound's risk. Recent advances in the scientific field, especially with the development of high‐throughput methods to quantify DNA damage, have influenced a change of approach in genotoxicity assessment. The in vitro MultiFlow® DNA Damage Assay is one such method which multiplexes γH2AX, p53, phospho‐histone H3 biomarkers into a single‐flow cytometric analysis (Bryce et al., [2016]: Environ Mol Mutagen 57:546–558). This assay was used to study human TK6 cells exposed to each of eight topoisomerase II poisons for 4 and 24 hr. Using PROAST v65.5, the Benchmark Dose approach was applied to the resulting flow cytometric datasets. With “compound” serving as covariate, all eight compounds were combined into a single analysis, per time point and endpoint. The resulting 90% confidence intervals, plotted in Log scale, were considered as the potency rank for the eight compounds. The in vitro MultiFlow data showed a maximum confidence interval span of 1Log, which indicates data of good quality. Patterns observed in the compound potency rank were scrutinized by using the expert rule‐based software program Derek Nexus, developed by Lhasa Limited. Compound sub‐classification and structural alerts were considered contributory to the potencies observed for the topoisomerase II poisons studied herein. The Topo II poison Adverse Outcome Pathway was evaluated with MultiFlow endpoints serving as Key Events. The step‐wise approach described herein can be considered as a foundation for risk assessment of compounds within a specific mode of action of interest. Environ. Mol. Mutagen. 2020. © 2020 Wiley Periodicals, Inc.
Fuzzy Adaptive Practical Fixed-Time Consensus for Second-Order Nonlinear Multiagent Systems Under Actuator Faults

This article concentrates upon the problem of practical fixed-time consensus for second-order nonlinear multiagent systems (MASs) under directed communication topology. The convergence time is independent of the initial condition. Both loss of effectiveness and bias fault are taken into account. Meanwhile, fuzzy-logic systems are introduced to approximate the unknown nonlinear functions. By the adding-a-power-integrator method, a distributed fuzzy adaptive practical fixed-time fault-tolerant control scheme is proposed. Then, the leader can be tracked in a settling time, and the consensus tracking errors converge to an adjustable neighborhood of the origin. Finally, two simulations are given to further illustrate the effectiveness of the theoretical result.
The Relationship Between Treatment Alliance, Social Climate, and Treatment Readiness in Long-Term Forensic Psychiatric Care: An Explorative Study

For patients in long-term forensic psychiatric care (LFPC), a continuous search for treatment possibilities remains important. An alternative viewpoint to these patients as being untreatable is considering them having low treatment readiness. Treatment readiness incorporates internal client-specific factors as well as factors in the therapeutic situation. In the therapeutic situation both social climate and therapeutic alliance are of positive influence on treatment outcome. In this explorative study of 38 male patients in Dutch LFPC, we found correlations with strong (Bayesian) evidence between internal factors of treatment readiness, treatment alliance, and “Therapeutic Hold,” which is a subscale of social climate. In a Bayesian linear regression analysis, however, therapeutic hold seemed to be the only strong predictor of internal treatment readiness. These results give way to further research into the factors specifically contributing to the found correlations, in order to create opportunities to enlarge treatment readiness for patients in forensic care.
Cortical fNIRS Responses Can Be Better Explained by Loudness Percept than Sound Intensity

Supplemental Digital Content is available in the text. Objectives: Functional near-infrared spectroscopy (fNIRS) is a brain imaging technique particularly suitable for hearing studies. However, the nature of fNIRS responses to auditory stimuli presented at different stimulus intensities is not well understood. In this study, we investigated whether fNIRS response amplitude was better predicted by stimulus properties (intensity) or individually perceived attributes (loudness). Design: Twenty-two young adults were included in this experimental study. Four different stimulus intensities of a broadband noise were used as stimuli. First, loudness estimates for each stimulus intensity were measured for each participant. Then, the 4 stimulation intensities were presented in counterbalanced order while recording hemoglobin saturation changes from cortical auditory brain areas. The fNIRS response was analyzed in a general linear model design, using 3 different regressors: a non-modulated, an intensity-modulated, and a loudness-modulated regressor. Results: Higher intensity stimuli resulted in higher amplitude fNIRS responses. The relationship between stimulus intensity and fNIRS response amplitude was better explained using a regressor based on individually estimated loudness estimates compared with a regressor modulated by stimulus intensity alone. Conclusions: Brain activation in response to different stimulus intensities is more reliant upon individual loudness sensation than physical stimulus properties. Therefore, in measurements using different auditory stimulus intensities or subjective hearing parameters, loudness estimates should be examined when interpreting results.