Miracle-dz/UniFAR-FTUs huggingface dataset:
DDX3: a relevant therapeutic target for lymphoma?

DDX3X is an RNA-helicase that unwinds RNA complexes and regulates mRNA translation [1]. The DDX3X protein is highly conserved between mice and humans (98%) and contains a helicase and an ATP-binding domain. The DDX3X gene is located on the X chromosome and escapes X-chromosome inactivation in human and mice. Consequently, females have two active DDX3X copies, while males carry only one, although the Y chromosome harbors a paralog called DDX3Y encoding a nearly identical protein (>90% homology). Recent large-scale sequencing studies revealed that DDX3X is mutated at significant percentages in many B cell malignancies: 30% of Burkitt Lymphoma (BL), 5% of diffuse large B cell lymphoma (DLBCL), 14% of primary mediastinal B cell lymphoma, as well as in 10% of Hodgkin’s Lymphoma, . The majority are loss of function (LOF) mutations located within sequences coding for the helicase domain and thus abrogating DDX3X enzymatic activity. Gong and collaborators discovered that DDX3X mutations occur with high frequencies in B cell lymphoma harboring a MYC translocation and are found almost exclusively in male patients [2]. It became clear from two recent studies that male malignant B cells with a DDX3X LOF aberrantly express DDX3Y protein, normally absent from human normal B cells [2,3]. Both studies concurred on the view that DDX3Y protein expression is required for the survival of lymphoma cells in the absence of a functional DDX3X. This validated the notion that DDX3X is an essential gene for B cell survival and its LOF is detrimental except in the presence of the male-specific DDX3Y protein [4,5]. DDX3Y mutations have never been reported in B cell lymphoma most likely because DDX3Y protein is not present in normal human B cells and thus a LOF would not confer a selective advantage for lymphoma outgrowth. These recent discoveries support the theory that DDX3 inhibition is toxic to cancerous B cells and can therefore be exploited for new therapeutic strategies.
Lipofibromatosis‐like neural tumors: Report of a case and review of 73 reported cases

Lipofibromatosis‐like neural tumors (LPF‐NTs) are a recently discovered group of spindle cell tumors defined by the presence of a lipofibromatosis‐like pattern, CD34 and/or S100 reactivity, and frequent neurotrophic receptor tyrosine kinase 1 (NTRK1) gene rearrangements. As new cases emerge, the spectrum of features observed in LPF‐NTs continues to evolve. Here we describe the case of an 11‐year‐old with LPF‐NT with a dermatofibrosarcoma protuberans‐like honeycomb pattern, CD34 and S100 co‐expression, and an NTRK1 rearrangement. We also review the clinical and molecular features of the 73 cases of LPF‐NT previously described in the literature.
Micropackaging Technologies for Integrated Microsystems: Applications to MEMS and MOEMS

Although MEMS technologies and device structures have made significant progress in the past three decades and have found widespread application in many areas, including Micro-Opto-Electro-Mechanical Systems (MOEMS), packaging and assembly techniques suitable for many of these emerging applications have not kept pace. Packaging is one of the most costly parts of microsystem manufacturing, and it is also often the first to fail or negatively influence the system response. This paper addresses the packaging and assembly challenges of microsystems and MEMS for different applications. Hermetic and vacuum micropackaging, wafer-level packaging and bonding, and miniature sealed interconnection and feedthrough technologies will be reviewed. Results from long-term accelerated testing, and from in-situ tests, especially in biological hosts, will also be discussed. Issues and challenges facing packaging of MOEMS will be discussed.
Allotropy of selenium nanoparticles: Colourful transition, synthesis, and biotechnological applications

Elemental selenium (Se0) nanomaterials undergo allotropic transition from thermodynamically‐unstable to more stable phases. This process is significantly different when Se0 nanoparticles (NPs) are produced via physico‐chemical and biological pathways. While the allotropic transition of physico‐chemically synthesized Se0 is fast (minutes to hours), the biogenic Se0 takes months to complete. The biopolymer layer covering biogenic Se0 NPs might be the main factor controlling this retardation, but this still remains an open question. Phylogenetically‐diverse bacteria reduce selenium oxyanions to red amorphous Se0 allotrope, which has low market value. Then, red Se0 undergoes allotropic transition to trigonal (metallic grey) allotrope, the end product having important industrial applications (e.g. semiconductors, alloys). Is it not yet clear whether biogenic Se0 presents any biological function, or it is mainly a detoxification and respiratory by‐product. The better understanding of this transition would benefit the recovery of Se0 NPs from secondary resources and its targeted utilization with respect to each allotropic stage. This review article presents and critically discusses the main physico‐chemical methods and biosynthetic pathways of Se0 (bio)mineralization. In addition, the article proposes a conceptual model for the resource recovery potential of trigonal selenium nanomaterials in the context of circular economy.
Da-Cheng-Qi decoction improves severe acute pancreatitis-associated acute lung injury by interfering with intestinal lymphatic pathway and reducing HMGB1-induced inflammatory response in rats

Abstract Context Da-Cheng-Qi Decoction (DCQD) has a significant effect on Severe Acute Pancreatitis-Associated Acute Lung Injury (SAP-ALI). Objective To explore the mechanism of DCQD in the treatment of SAP-ALI based on intestinal barrier function and intestinal lymphatic pathway. Materials and methods Forty-five Sprague-Dawley rats were divided into three groups: sham operation, model, and DCQD. The SAP model was induced by a retrograde infusion of 5.0% sodium taurocholate solution (1 mg/kg) at a constant rate of 12 mL/h using an infusion pump into the bile-pancreatic duct. Sham operation and model group were given 0.9% normal saline, while DCQD group was given DCQD (5.99 g/kg/d) by gavage 1 h before operation and 1, 11 and 23 h after operation. The levels of HMGB1, RAGE, TNF-α, IL-6, ICAM-1, d-LA, DAO in blood and MPO in lung were detected using ELISA. The expression of HMGB1, RAGE, NF-κB p65 in mesenteric lymph nodes and lung were determined. Results Compared with SAP group, DCQD significantly reduced the histopathological scoring of pancreatic tissue (SAP, 2.80 ± 0.42; DCQD, 2.58 ± 0.52), intestine (SAP, 3.30 ± 0.68; DCQD, 2.50 ± 0.80) and lung (SAP, 3.30 ± 0.68; DCQD, 2.42 ± 0.52). DCQD reduced serum HMGB1 level (SAP, 134.09 ± 19.79; DCQD, 88.05 ± 9.19), RAGE level (SAP, 5.05 ± 1.44; DCQD, 2.13 ± 0.54). WB and RT-PCR showed HMGB1-RAGE pathway was inhibited by DCQD (p < 0.01). Discussion and conclusions DCQD improves SAP-ALI in rats by interfering with intestinal lymphatic pathway and reducing HMGB1-induced inflammatory response.
A Comparison of Several Techniques to Assign Heights to Cloud Tracers

Abstract Satellite-derived cloud-motion vector (CMV) production has been troubled by inaccurate height assignment of cloud tracers, especially in thin semitransparent clouds. This paper presents the results of an intercomparison of current operational height assignment techniques. Currently, heights are assigned by one of three techniques when the appropriate spectral radiance measurements are available. The infrared window (IRW) technique compares measured brightness temperatures to forecast temperature profiles and thus infers opaque cloud levels. In semitransparent or small subpixel clouds, the carbon dioxide (CO2) technique uses the ratio of radiances from different layers of the atmosphere to infer the correct cloud height. In the water vapor (H2O) technique, radiances influenced by upper-tropospheric moisture and IRW radiances are measured for several pixels viewing different cloud amounts, and their linear relationship is used to extrapolate the correct cloud height. The results presented in this p.
Blood soluble Fas concentrations and ischemic stroke patient mortality

ABSTRACT Background Fas is a major receptor for cell death by apoptosis. Higher blood concentrations of soluble Fas (sFas) have been reported in patients with ischemic stroke compared to control subjects. The aim of this study was to explore the existence or not of an association between blood sFas concentrations and mortality in patients with ischemic stroke. Methods This study included patients admitted to Intensive Care Units with severe and malignant middle cerebral artery infarction (MCAI), defined as acute infarction, in more than 50% of this territory on computed tomography and less than 9 points on the Glasgow Coma Scale (GCS). Serum sFas levels were determined at the time of diagnosis of MMCAI. Results Non-surviving severe MMCAI patients (n = 27) showed lower platelet count (p = 0.004), higher serum sFas (p < 0.001), and lower GCS (p = 0.001) compared to surviving patients (n = 27). Multiple logistic regression found an association of serum sFas levels and mortality at 30 days (OR = 1.015; 95% CI = 1.002–1.027; p = 0.02) after control for CGS and platelet count. Conclusions The main novelty of our study was the existence of an association between high blood sFas concentrations and mortality in patients with ischemic stroke.
Mastectomy is a safe procedure in transgender men with a history of breast reduction

Abstract Little is known about the safety and surgical outcomes of mastectomy after breast reduction in the trans male population. Several concerns have been voiced that performing mastectomy with prior breast reduction surgery, increases the risk for complications and revision surgery. All transgender men with a history of breast reduction, who underwent a mastectomy at our center between 01-1990 and 01-2021 were identified from our hospital registry. A retrospective chart study was conducted recording surgical characteristics, surgical complications, revision surgery, and clinical follow-up. A total of 1362 subcutaneous mastectomies were performed between 01-1990 and 01-2021. A total of 36 (2.6%) individuals were included (35 bilateral and 1 unilateral breast reduction). The mean age at mastectomy was 37 ± 10 years, and the median time between breast reduction and mastectomy was 6.3 years (range 1.0–31.1). Most individuals underwent a Wise-pattern breast reduction (91%) and a double incision mastectomy with free nipple grafts (86%). Following mastectomy, one acute reoperation was performed because of hemorrhage (3%). Partial pedicled nipple necrosis was seen in 7% and (partial) non-take of nipple grafts in 4%. Scar revisions were performed in 9%, dogear corrections in 20%, and both nipple corrections, and contour corrections in 6%. When comparing the outcomes in literature for surgical complications, scar revision, contour correction or nipple areolar complex revision, no clear disadvantage seems to be present when performing mastectomy after breast reduction. Mastectomy is a safe procedure in transgender men with a history of breast reduction.
Auditory rehabilitation after temporal bone fracture with cochlear implants – a case control study

Objectives: Temporal bone fracture can cause posttraumatic deafness. Sequelae like ossification or obliteration of the cochlea can impact the outcome of cochlear implantation. This study highlights the effect of localisation of the fracture to morphologic, electric and functional criteria. Methods: The study group consists of patients suffering from hearing loss caused by temporal bone fracture (n = 61 ears). Patients were divided into otic capsule sparing (OCS) and otic capsule involving (OCI) fractures. The OCI group was additionally divided into subgroups with or without signs of ossification inside the cochlea. Postoperative imaging, hearing tests and electrode impedances were analysed. Results: The results of postoperative hearing rehabilitation showed lower speech understanding scores for the OCI group, especially for the ossification group. OCI fractures with signs of ossification showed increased impedances. Patients in the OCI group suffered more frequently from facial nerve stimulation (FNS). FNS was most frequently observed within the ossification group. Conclusion: Cochlear implantation in patients with temporal bone fracture is adequate therapy for the treatment of fracture-induced deafness. In long-term observation, these patients show comparable results with regular cochlear implant (CI) patients. Implantation should be performed as soon as possible after hearing loss, before obstructing obliteration or ossification of the cochlea start.
Mobile digital gait analysis objectively measures progression in hereditary spastic paraplegia

Progressive spasticity and gait impairment is the functional hallmark of hereditary spastic paraplegia (HSP), but due to inter‐individual variability, longitudinal studies on its progression are scarce. We investigated the progression of gait deficits via mobile digital measurements in conjunction with clinical and patient‐reported outcome parameters. Our cohort included adult HSP patients (n = 55) with up to 77 months of follow‐up. Gait speed showed a significant association with SPRS progression. Changes in stride time and gait variability correlated to fear of falling and quality of life, providing evidence that gait parameters are meaningful measures of HSP progression.
The Extracellular Electron Transport Pathway Reduces Copper for Sensing by the CopRS Two-Component System under Anaerobic Conditions in Listeria monocytogenes

Two-component extracellular copper sensing from the periplasm of Gram-negative bacteria has been well studied, but copper detection at the cell surface of the Gram-positive L. monocytogenes is less understood. Collectively, our results show that EET is most active under anaerobic conditions and reduces Cu2+ and Ag1+ to, respectively, generate or remove the monovalent ligands that directly bind to CopS and lead to the induction of lipoprotein remodeling genes. ABSTRACT The renowned antimicrobial activity of copper stems in part from its ability to undergo redox cycling between Cu1+/2+ oxidation states. Bacteria counter copper toxicity with a network of sensors that often include two-component signaling systems to direct transcriptional responses. As in typical two-component systems, ligand binding by the extracellular domain of the membrane bound copper sensor component leads to phosphorylation and activation of the cognate response regulator transcription factor. In Listeria monocytogenes, the plasmid-borne CopRS two-component system upregulates both copper resistance and lipoprotein remodeling genes upon copper challenge, but the oxidation state of copper bound by CopS is unknown. Herein, we show CopS utilizes a triad of key residues (His-His-Phe) that are predicted to be at the dimerization interface and that are analogous with the Escherichia coli CusS copper sensor to specifically bind Cu1+/Ag1+ and activate CopR transcription. We demonstrate Cu2+ only induces CopRS if first reduced by electron transport systems, as strains lacking menaquinone carriers were unable to respond to Cu2+. The flavin-dependent extracellular electron transport system (EET) was the main mechanism for metal reduction, capable of either generating inducing ligand (Cu2+ to Cu1+) or removing it by precipitation (Ag1+ to Ag0). We show that EET flux is directly proportional to the rate of Cu2+ reduction and that since EET activity is low under oxygenated conditions when a competing respiratory chain is operating, CopRS signaling in turn is activated only under anaerobic conditions. EET metal reduction thus sensitizes cells to copper while providing resistance to silver under anaerobic growth. IMPORTANCE Two-component extracellular copper sensing from the periplasm of Gram-negative bacteria has been well studied, but copper detection at the cell surface of the Gram-positive L. monocytogenes is less understood. Collectively, our results show that EET is most active under anaerobic conditions and reduces Cu2+ and Ag1+ to, respectively, generate or remove the monovalent ligands that directly bind to CopS and lead to the induction of lipoprotein remodeling genes. This reducing activity regulates CopRS signaling and links the upregulation of copper resistance genes with increasing EET flux. Our studies provide insight into how a two-component copper sensing system is integrated into a model monoderm Firmicute to take cues from the electron transport chain activity.
Test accuracy of artificial intelligence-based grading of fundus images in diabetic retinopathy screening: A systematic review

Objectives To systematically review the accuracy of artificial intelligence (AI)-based systems for grading of fundus images in diabetic retinopathy (DR) screening. Methods We searched MEDLINE, EMBASE, the Cochrane Library and the ClinicalTrials.gov from 1st January 2000 to 27th August 2021. Accuracy studies published in English were included if they met the pre-specified inclusion criteria. Selection of studies for inclusion, data extraction and quality assessment were conducted by one author with a second reviewer independently screening and checking 20% of titles. Results were analysed narratively. Results Forty-three studies evaluating 15 deep learning (DL) and 4 machine learning (ML) systems were included. Nine systems were evaluated in a single study each. Most studies were judged to be at high or unclear risk of bias in at least one QUADAS-2 domain. Sensitivity for referable DR and higher grades was ≥85% while specificity varied and was <80% for all ML systems and in 6/31 studies evaluating DL systems. Studies reported high accuracy for detection of ungradable images, but the latter were analysed and reported inconsistently. Seven studies reported that AI was more sensitive but less specific than human graders. Conclusions AI-based systems are more sensitive than human graders and could be safe to use in clinical practice but have variable specificity. However, for many systems evidence is limited, at high risk of bias and may not generalise across settings. Therefore, pre-implementation assessment in the target clinical pathway is essential to obtain reliable and applicable accuracy estimates.
Mass Spectrometry Reveals High Levels of Hydrogen Peroxide in Pancreatic Cancer Cells.

Reactive oxygen species (ROS) are critical for many cellular functions, and dysregulation of ROS involves the development of multiple types of tumors, including pancreatic cancer. However, ROS have been grouped into a single biochemical entity for a long time, and the specific roles of certain types of ROS in tumor cells (e.g., pancreatic ductal adenocarcinoma (PDAC)) have not been systematically investigated. In this work, a highly sensitive and accurate mass spectrometry-based method was applied to study PDAC cells of humans and of genetically modified animals. The results show that the oncogenic KRAS mutation promotes the accumulation of hydrogen peroxide (H2O2) rather than superoxide or hydroxyl radicals in pancreatic cancer cells. We further identified that the enriched H2O2 modifies cellular metabolites and promotes the survival of pancreatic cancer cells. These findings highlight the specific roles of H2O2 in pancreatic cancer development, which may provide new directions for pancreatic cancer therapy.
A multiplex fluorescence-based loop-mediated isothermal amplification assay for identifying chicken parvovirus, chicken infectious anaemia virus, and fowl aviadenovirus serotype 4

ABSTRACT Chicken parvovirus (ChPV), chicken infectious anaemia virus (CIAV) and fowl adenovirus serotype 4 (FAdV-4) are avian viruses that have emerged in recent years and have endangered the global poultry industry, causing great economic loss. In this study, a multiplex fluorescence-based loop-mediated isothermal amplification (mLAMP) assay for detecting ChPV, CIAV and FAdV-4 was developed to simultaneously diagnose single and mixed infections in chickens. Three primer sets and composite probes were designed according to the conserved regions of the NS gene of ChPV, VP1 gene of CIAV and hexon gene of FAdV-4. Each composite probe was labelled with a different fluorophore, which was detached to release the fluorescence signal after amplification. The target viruses were distinguished based on the colour of the mLAMP products. The mLAMP assay was shown to be sensitive, with detection limits of 307 copies of recombinant plasmids containing the ChPV target genes, 749 copies of CIAV and 648 copies of FAdV-4. The assay exhibited good specificity and no cross-reactivity with other symptomatically related avian viruses. When used on field materials, the results of the mLAMP assay were in 100% agreement with those of the previously published PCR assay. The mLAMP assay is rapid, economical, sensitive and specific, and the results of amplification are directly observable by eye. Therefore, the mLAMP assay is a useful tool for the clinical detection of ChPV, CIAV and FAdV-4 and can be applied in rural areas.
An AUC-based Active Learning Algorithm via LogitBoost for Binary Classification

When labeling subjects is quite expensive, to incorporate both labeled and unlabeled data in training a classifier becomes a common strategy. Semi-supervised learning is widely applied for this situation and typically uses a small amount of labeled data with a large amount of unlabeled data to train classifiers. Active learning, one kind of semi-supervised learning, is able to interactively query some information to get new subjects' labels/classes and is able to reduce cost because only the selected subjects need to be exanimated labels. Additionally, boosting algorithm is an ensemble learning algorithm for reducing bias and variations in supervised learning. Area under ROC curve is a widely used criterion for evaluating the predictive performance of a classifier. Hence, in this paper, we proposed a boosting-base active learning algorithm with optimizing AUC for binary classification. The simulation results show that the proposed method can achieve good predictive performance with using fewer samples.
Health Literacy of Surrogates and Communication Issues in Palliative Care Conversations in Critical Care

Worldwide, 56.8 million persons are estimated to require palliative care. Critically ill patients benefit from palliative care by improving their quality of life through symptom management. Resistance to palliative care exists from surrogate decision-makers because of low health literacy and communication issues with providers. This research reviewed the literature to identify how health literacy and health care communication influenced palliative care conversations with decision-making surrogates and health outcomes of critically ill patients. The review included articles between 2011 and 2022 using the terms communication, health literacy, palliative care, critical care, intensive care, ICU, surrogate decision maker, family, and caregiver in PubMed, CINAHL, and Google Scholar. Fourteen articles were included. Quality was assessed through Joanna Briggs Institute appraisal tools. Health literacy of surrogates was not found to be significant for patient outcomes. However, there were significant differences between clinician and surrogate communication influenced by surrogates' previous health care experiences. Early communication about prognosis was important for surrogates. Structured communication approaches were preferred by surrogates. Limitations of the review included primarily White participants, small variability of research sites, and a few number of articles. Future research needs to study the effects of surrogate health literacy of critically ill patients on willingness to accept palliative care.