Miracle-dz/UniFAR-FTUs huggingface dataset:
The value of cytology in distinguishing malignant mesothelioma: An institutional experience of 210 cases reclassified according to the International System for Reporting Serous Fluid Cytopathology (ISRSFC)

Malignant mesothelioma (MM) is usually diagnosed by histological examination of tissue samples; however, effusion cytology offers an opportunity to identify a strong possibility for mesothelioma diagnosis at an early stage. We conducted a retrospective analysis of cytological specimens from a large series of histologically proven MM diagnosed over 19 years. The cases were reviewed and reclassified according to the International System for Reporting Serous Fluid Cytopathology (ISRSFC).
Free flap transplantation combined with Ilizarov bone transport for the treatment of severe composite tibial and soft tissue defects

Objective To evaluate the clinical efficacy of free flap transplantation combined with Ilizarov bone transport in the treatment of severe composite tibial and soft tissue defects. Methods We retrospectively analyzed the clinical data of 40 patients with severe composite tibial and soft tissue defects who underwent free flap transplantation combined with Ilizarov bone transport. The clinical efficacy was evaluated according to the following criteria: success rate of wound repair by free flap transplantation, incidence or recurrence rate of deep infection, healing rate of bone defects and external fixation index, incidence of complications, and functional score of affected extremities. Results All infections were generally well controlled by radical debridement and negative-pressure therapy, and all 40 patients’ wounds healed after repair and reconstruction of the tibia and soft tissues. Postoperative complications were alleviated by active treatment. The mean external fixation time was 12.83 ± 2.85 months, and the external fixation index was 1.55 m/cm. According to the Association for the Study and Application of Methods of Ilizarov (ASAMI) score, an excellent or good functional outcome was attained in 85% of patients. Conclusion Free flap transplantation combined with Ilizarov bone transport is an effective treatment for severe composite tibial and soft tissue defects.
Separation and Purification of Chlorogenic Acid from Lonicera Japonica Thunb.

Objectivel A method for the efficient preparati ve purificati on of Chlorogenic acid in the medicinal plant Lonicera japonica Thunb. has been developed. Method The separation and purification of chlorogenic aci d was achiev ed by a combination of polyamide column chromatography and sephadex LH-20 chrom atography. Water extract of Lonicera japonica Thunb. was isolated by polyamide c olumn chromatography, followed by Sephades LH-20 chromatography using a solvent system of acetone-water(5:5). Results Identification of Chlorogenic acid was performed by LC ESI MS, IR and UV-Vis. The structure of the product w as further confirmed by comparison with authentic sample and the purity of chlor ogenic acid purified was great than 98%. Conclusion This purificatio n protocol has significa ntly enhanced the throughput and simplified the isolation and purification opera tion, provided high-quality products for biological screening.
De Novo Radiomics Approach Using Image Augmentation and Features From T1 Mapping to Predict Gleason Scores in Prostate Cancer

Supplemental digital content is available in the text. Objectives The aims of this study were to discriminate among prostate cancers (PCa's) with Gleason scores 6, 7, and ≥8 on biparametric magnetic resonance imaging (bpMRI) of the prostate using radiomics and to evaluate the added value of image augmentation and quantitative T1 mapping. Materials and Methods Eighty-five patients with subsequently histologically proven PCa underwent bpMRI at 3 T (T2-weighted imaging, diffusion-weighted imaging) with 66 patients undergoing additional T1 mapping at 3 T. The PCa lesions as well as the peripheral and transition zones were segmented pixel by pixel in multiple slices of the 3D MRI data sets (T2-weighted images, apparent diffusion coefficient, and T1 maps). To increase the size of the data set, images were augmented for contrast, brightness, noise, and perspective multiple times, effectively increasing the sample size 10-fold, and 322 different radiomics features were extracted before and after augmentation. Four different machine learning algorithms, including a random forest (RF), stochastic gradient boosting (SGB), support vector machine (SVM), and k-nearest neighbor, were trained with and without features from T1 maps to differentiate among 3 different Gleason groups (6, 7, and ≥8). Results Support vector machine showed the highest accuracy of 0.92 (95% confidence interval [CI], 0.62–1.00) for classifying the different Gleason scores, followed by RF (0.83; 95% CI, 0.52–0.98), SGB (0.75; 95% CI, 0.43–0.95), and k-nearest neighbor (0.50; 95% CI, 0.21–0.79). Image augmentation resulted in an average increase in accuracy between 0.08 (SGB) and 0.48 (SVM). Removing T1 mapping features led to a decline in accuracy for RF (−0.16) and SGB (−0.25) and a higher generalization error. Conclusions When data are limited, image augmentations and features from quantitative T1 mapping sequences might help to achieve higher accuracy and lower generalization error for classification among different Gleason groups in bpMRI by using radiomics.
Silylation of Deoxynucleotide Analog Yields an Orally Available Drug with Antileukemia Effects

DNA methyltransferase inhibitors have improved the prognosis of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, because these agents are easily degraded by cytidine deaminase (CDA), they must be administered intravenously or subcutaneously. Recently, two orally bioavailable DNA methyltransferase inhibitors, CC-486 and ASTX727, were approved. In previous work, we developed 5-O-trialkylsilylated decitabines that resist degradation by CDA. However, the effects of silylation of a deoxynucleotide analog and enzymatic cleavage of silylation have not been fully elucidated. Enteric administration of OR21 in a cynomolgus monkey model led to high plasma concentrations and hypomethylation, and in a mouse model, oral administration of enteric-coated OR21 led to high plasma concentrations. The drug became biologically active after release of decitabine (DAC) from OR21 following removal of the 5′-O-trisilylate substituent. Toxicities were tolerable and lower than those of DAC. Transcriptome and methylome analysis of MDS and AML cell lines revealed that OR21 increased expression of genes associated with tumor suppression, cell differentiation, and immune system processes by altering regional promoter methylation, indicating that these pathways play pivotal roles in the action of hypomethylating agents. OR21 induced cell differentiation via upregulation of the late cell differentiation drivers CEBPE and GATA-1. Thus, silylation of a deoxynucleotide analog can confer oral bioavailability without new toxicities. Both in vivo and in vitro, OR21 exerted antileukemia effects, and had a better safety profile than DAC. Together, our findings indicate that OR21 is a promising candidate drug for phase I study as an alternative to azacitidine or decitabine.
Caloric and galvanic vestibular stimulation for the treatment of Parkinson’s disease: rationale and prospects

ABSTRACT Introduction: Deeply embedded within the inner ear, the sensory organs of the vestibular system are exquisitely sensitive to the orientation and movement of the head. This information constrains aspects of autonomic reflex control as well as higher-level processes involved in cognition and affect. The anatomical pathways that underline these functional interactions project to many cortical and sub-cortical brain areas, and the question arises as to whether they can be therapeutically harnessed. Areas covered: The body of work reviewed here indicates that the controlled application of galvanic or thermal current to the vestibular end-organs can modulate activity throughout the ascending vestibular network and, under appropriate conditions, reduce motor and non-motor symptoms associated with Parkinson’s disease, a disease of growing prevalence and continued unmet clinical need. Expert opinion: The appeal of vestibular stimulation in Parkinson’s disease is underpinned by its noninvasive nature, favorable safety profile, and capacity for home-based administration. Clinical adoption now rests on the demonstration of cost-effectiveness and on the commercial availability of suitable devices, many of which are only permitted for research use or lack functionality. Dose optimization and mechanisms-of-action studies are also needed, along with a broader awareness amongst physicians of its therapeutic potential.
SPP-CPI: Predicting Compound–Protein Interactions Based On Neural Networks

Identifying interactions between compound and protein is a substantial part of the drug discovery process. Accurate prediction of interaction relationships can greatly reduce the time of drug development. The uniqueness of our method lies in three aspects:1) it represents a compound with a distance matrix. A distance matrix can capture the structural information, compared with the SMILES string. On the other hand, a distance matrix does not require complex data preprocessing for the molecular structure as the molecular graph representation, and is easier to obtain; 2) it uses SPP(Spatial pyramid pooling)-net to extract compound features, which has been successfully applied in image classification; and 3) it extracts protein features through the natural language processing method (doc2vec) to obtain sequence semantic information. We evaluated our method on three benchmark datasets—human, C.elegans, and DUDE—and the experimental results demonstrate that our proposed model presents competitive performance against state-of-the-art predictors. We also carried out drug–drug interaction (DDI) experiments to verify the strong potential of distance matrix as molecular characteristics. The source code and datasets are available at https://github.com/lxlsu/SPP_CPI.
Early activity in mechanically ventilated patients – a meta-analysis

E-mail: heikas@ous-hf.no Section of Orthopaedic Rehabilitation Department of Orthopaedics Oslo University Hospital She has contributed to the study concept and design, to data collection, analysis and interpretation, to the drafting/revision of the manuscript, and has approved the submitted version. She also made intellectual contributions to the literature search. Hanna Eikås Klem, MSc in health sciences from the University of Oslo, specialist physiotherapist and head of unit. The author has completed the ICMJE form and declares no conflicts of interest.
To disclose or not to disclose? Peer workers impact on a culture of safe disclosure for mental health professionals with lived experience.

The presence of peer workers in multi-disciplinary environments has rapidly increased in recent years, yet the impact of peer work on other mental health roles is largely unknown. This article explores the presence of peer workers within multi-disciplinary environments, with a specific focus on the possible impact of this presence on the culture of disclosure for mental health professionals with lived experiences of mental health challenges. Semi-structured focus groups and interviews were conducted with 132 participants at five organizations across the United States. Participants self-identified as being employed in a range of roles including management, mental health professionals, designated peer workers, and designated peer leadership positions. Findings suggest intentionally employing peers and using peer values to address stigma toward mental health professionals improves the culture of disclosure. In work environments where peer-led initiatives were featured, mental health professionals felt safer disclosing their own lived experience to their colleagues and supervisors. Recommendations include the use of parallel strategies to promote the perceived value of peers and to implement peer-led training for both supervisors and professionals to model a workplace culture that promotes and supports self-disclosure in the organization. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
First experience in clinical application of hyperspectral endoscopy for evaluation of colonic polyps

Early detection and resection of adenomatous polyps prevents their progression to colorectal cancer (CRC), significantly improving patient outcomes. Polyps are typically identified and removed during white‐light colonoscopy. Unfortunately, the rate of interval cancers that arise between CRC screening events remains high, linked to poor visualization of polyps during screening and incomplete polyp removal. Here, we sought to evaluate the potential of a hyperspectral endoscope (HySE) to enhance polyp discrimination for detection and resection. We designed, built and tested a new compact HySE in a proof‐of‐concept clinical study. We successfully collected spectra from three tissue types in seven patients undergoing routine colonoscopy screening. The acquired spectral data from normal tissue and polyps, both pre‐ and post‐ resection, were subjected to quantitative analysis using spectral angle mapping and machine learning, which discriminated the data by tissue type, meriting further investigation of HySE as a clinical tool.
First‐in‐human trial to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of STR‐324, a dual enkephalinase inhibitor for pain management

Dual enkephalinase inhibitors (DENKIs) are involved in the regulation of nociception via opioid receptors. The novel compound STR‐324 belongs to the DENKI pharmacological class. This first‐in‐human study evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of STR‐324 in healthy male participants.
Reproductive outcomes in women with mild intrauterine adhesions; a systematic review and meta-analysis

Abstract Background Moderate to severe intrauterine adhesions (IUAs) may greatly impact fertility, predisposing to pregnancy and obstetric complications. The impact of mild IUAs on reproductive performance remains unclear. A systematic review and meta-analysis was performed to examine the long-term reproductive outcomes in women with hysteroscopic identified and treated mild IUAs mild intrauterine adhesions (IUAs) Methods An electronic literature search was conducted using MEDLINE and EMBASE from inception to June 2019. All prospective cohort, cross-sectional studies or randomized controlled trials Clinical trials in which reproductive outcomes of women with mild IUAs, were reported were included. Results Five studies, reporting on reproductive outcomes of 229 women with hysteroscopic identified and treated mild IUAs, were included. The pregnancy rate was 62.3% (142 of 228; 95% CI: 0.55–0.72, I 2 25%, p = .21) and in 86.6% (123 of 142) a live birth was encountered (95% CI: 0.71–0.97) with 83.1% (108 out of 130) term deliveries (95% CI: 0.53–0.95). A miscarriage was reported in 10% (13 of 130; 95% CI: 0.02–0.26). Due to the lack of a control group, reproductive outcomes were compared to a general population. Pregnancy and live birth rates were significantly lower in women with identified and treated mild IUAs, 90% versus 62.3% and respectively 99.5% versus 86.6%. The miscarriage rate was similar. Data on obstetric and neonatal outcomes are lacking. Conclusions Women with hysteroscopic identified and treated mild IUAs seem to have lower pregnancy and live birth rate compared to the general population. Future studies consisting of a large cohort of women with hysteroscopic identified and treated IUAs with structural follow-up and a control group are needed to confirm our findings.
The circadian-controlled PIF8–BBX28 module regulates petal senescence in rose flowers by governing mitochondrial ROS homeostasis at night

Abstract Reactive oxygen species (ROS) are unstable reactive molecules that are toxic to cells. Regulation of ROS homeostasis is crucial to protect cells from dysfunction, senescence, and death. In plant leaves, ROS are mainly generated from chloroplasts and are tightly temporally restricted by the circadian clock. However, little is known about how ROS homeostasis is regulated in nonphotosynthetic organs, such as petals. Here, we showed that hydrogen peroxide (H2O2) levels exhibit typical circadian rhythmicity in rose (Rosa hybrida) petals, consistent with the measured respiratory rate. RNA-seq and functional screening identified a B-box gene, RhBBX28, whose expression was associated with H2O2 rhythms. Silencing RhBBX28 accelerated flower senescence and promoted H2O2 accumulation at night in petals, while overexpression of RhBBX28 had the opposite effects. RhBBX28 influenced the expression of various genes related to respiratory metabolism, including the TCA cycle and glycolysis, and directly repressed the expression of SUCCINATE DEHYDROGENASE 1, which plays a central role in mitochondrial ROS (mtROS) homeostasis. We also found that PHYTOCHROME-INTERACTING FACTOR8 (RhPIF8) could activate RhBBX28 expression to control H2O2 levels in petals and thus flower senescence. Our results indicate that the circadian-controlled RhPIF8–RhBBX28 module is a critical player that controls flower senescence by governing mtROS homeostasis in rose.
TDP‐43 proteinopathy occurs independently of autophagic substrate accumulation and underlies nuclear defects in Niemann‐Pick C disease

Neuronal cytoplasmic inclusions of TAR‐DNA binding protein of 43 kDa (TDP‐43) are a pathological hallmark of diverse neurodegenerative disorders, yet the processes that mediate their formation and their functional significance remain incompletely understood. Both dysfunction in autophagy and neuroinflammation have been linked to TDP‐43 mislocalisation. Here, we investigate TDP‐43 proteinopathy in Niemann‐Pick type C disease (NPC), an autosomal recessive lysosomal storage disease (LSD) distinguished by the accumulation of unesterified cholesterol within late endosomes and lysosomes. NPC is characterised by neurodegeneration, neuroinflammation and multifocal disruption of the autophagy pathway.
Characterization of oral and cloacal microbial communities in cold-stunned Kemp’s ridley sea turtles (Lepidochelys kempii) during the time course of rehabilitation

Microbial communities of animals play a role in health and disease, including immunocompromised conditions. In the northeastern United States, cold-stunning events often cause endangered Kemp’s ridley turtles (Lepidochelys kempii) to become stranded on beaches in autumn. These sea turtles are admitted to rehabilitation facilities when rescued alive and are presumed immunocompromised secondary to hypothermia. To better understand the role that microbes play in the health of cold-stunned sea turtles, we characterized the oral and cloacal microbiome from Kemp’s ridley turtles at multiple timepoints during rehabilitation, from admission to pre-release, by using Illumina sequencing to analyze the 16S rRNA gene. Microbial communities were distinct between body sites and among turtles that survived and those that died. We found that clinical parameters such as presence of pneumonia or values for various blood analytes did not correlate with oral or cloacal microbial community composition. We also investigated the effect of antibiotics on the microbiome during rehabilitation and prior to release and found that the type of antibiotic altered the microbial community composition, yet overall taxonomic diversity remained the same. The microbiome of cold-stunned Kemp’s ridley turtles gradually changed through the course of rehabilitation with environment, antibiotics, and disease status all playing a role in those changes and ultimately the release status of the turtles.
Neurocognitive abilities associated with antisocial behavior with and without callous-unemotional traits in a community sample.

OBJECTIVE Antisocial behavior (aggression, rule breaking) is associated with lower intelligence and executive function deficits. Research has not clarified whether these associations differ with the presence of callous-unemotional (CU) traits, particularly within levels of antisocial behavior observed in the community. METHOD We examined whether antisocial behavior and CU traits were differentially associated with intelligence and executive function metrics in 474 adolescent twins (Mean age = 14.18; SD = 2.20) sampled from birth records to represent youth in the community living in neighborhoods with above average levels of poverty. Intelligence was assessed using standardized scores from the Shipley-2. Executive function was assessed using Go/No-Go and Stop Signal tasks. RESULTS Neither antisocial behavior, nor CU traits alone, were associated with cognitive functioning when accounting for demographic factors. However, antisocial behavior and CU traits interacted to predict reaction time variability. At low levels of CU traits, antisocial behavior was associated with higher reaction time variability (traditionally thought to reflect worse sustained attention). At high levels of CU traits, antisocial behavior was associated with lower reaction time variability (thought to reflect better sustained attention). CONCLUSION Elevated antisocial behavior and CU traits may be characterized by a distinct neurocognitive profile compared to elevated antisocial behavior in isolation. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Comparative Hepatic and Intestinal Metabolism and Pharmacodynamics of Statins

This study aimed to comprehensively investigate the in vitro metabolism of statins. The metabolism of clinically relevant concentrations of atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin, and their metabolites were investigated using human liver microsomes (HLMs), human intestine microsomes (HIMs), liver cytosol, and recombinant cytochrome P450 enzymes. We also determined the inhibitory effects of statin acids on their pharmacological target, 3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase. In HLMs, statin lactones were metabolized to a much higher extent than their acid forms. Atorvastatin lactone and simvastatin (lactone) showed extensive metabolism [intrinsic clearance (CLint) values of 3700 and 7400 µl/min per milligram], whereas the metabolism of the lactones of 2-hydroxyatorvastatin, 4-hydroxyatorvastatin, and pitavastatin was slower (CLint 20–840 µl/min per milligram). The acids had CLint values in the range <0.1–80 µl/min per milligram. In HIMs, only atorvastatin lactone and simvastatin (lactone) exhibited notable metabolism, with CLint values corresponding to 20% of those observed in HLMs. CYP3A4/5 and CYP2C9 were the main statin-metabolizing enzymes. The majority of the acids inhibited HMG-CoA reductase, with 50% inhibitory concentrations of 4–20 nM. The present comparison of the metabolism and pharmacodynamics of the various statins using identical methods provides a strong basis for further application, e.g., comparative systems pharmacology modeling. SIGNIFICANCE STATEMENT The present comparison of the in vitro metabolic and pharmacodynamic properties of atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin and their metabolites using unified methodology provides a strong basis for further application. Together with in vitro drug transporter and clinical data, the present findings are applicable for use in comparative systems pharmacology modeling to predict the pharmacokinetics and pharmacological effects of statins at different dosages.