Miracle-dz/UniFAR-FTUs huggingface dataset:
A wave of monocytes is recruited to replenish the long-term Langerhans cell network after immune injury

Following immune damage in the epidermis, monocytes from the circulation give rise to epidermal Langerhans cells. Resurrecting sentinels in the skin Langerhans cells are resident innate immune cells in the skin that play essential roles in promoting local immune responses and in maintaining skin homeostasis. Langerhans cells arise from fetal progenitors that seed the skin early in development. Here, Ferrer et al. have used a hematopoietic stem cell transplant model to examine the consequences of immune damage and loss of Langerhans cells in adult mouse skin. They report that monocytes from the blood infiltrate the skin and eventually replenish the Langerhans cell network, albeit the process by which monocytes give rise to Langerhans cells is not particularly efficient. Their findings are in agreement with studies reporting the ability of monocytes to replenish tissue-resident macrophages at other sites. A dense population of embryo-derived Langerhans cells (eLCs) is maintained within the sealed epidermis without contribution from circulating cells. When this network is perturbed by transient exposure to ultraviolet light, short-term LCs are temporarily reconstituted from an initial wave of monocytes but thought to be superseded by more permanent repopulation with undefined LC precursors. However, the extent to which this process is relevant to immunopathological processes that damage LC population integrity is not known. Using a model of allogeneic hematopoietic stem cell transplantation, where alloreactive T cells directly target eLCs, we have asked whether and how the original LC network is ultimately restored. We find that donor monocytes, but not dendritic cells, are the precursors of long-term LCs in this context. Destruction of eLCs leads to recruitment of a wave of monocytes that engraft in the epidermis and undergo a sequential pathway of differentiation via transcriptionally distinct EpCAM+ precursors. Monocyte-derived LCs acquire the capacity of self-renewal, and proliferation in the epidermis matched that of steady-state eLCs. However, we identified a bottleneck in the differentiation and survival of epidermal monocytes, which, together with the slow rate of renewal of mature LCs, limits repair of the network. Furthermore, replenishment of the LC network leads to constitutive entry of cells into the epidermal compartment. Thus, immune injury triggers functional adaptation of mechanisms used to maintain tissue-resident macrophages at other sites, but this process is highly inefficient in the skin.
Programmable CRISPR-responsive smart materials

A CRISPR set of materials CRISPR technology is best known as a gene editing tool. English et al. developed a group of stimuli-responsive hydrogels to respond to the programmable nuclease Cas12a (see the Perspective by Han et al.). The materials undergo molecular to macroscopic changes after Cas12a-dependent cleavage of double- or single-stranded DNA integrated into the gel. The authors show controlled release of particles linked to or imprisoned within the DNA, degradation of a gel with DNA solely forming the cross-links, and permeabilization of a gel with DNA partially forming the cross-links. These tools allow for the production of materials that release encapsulated nanoparticles and cells, act as degradable fuses, and enable remote radio-frequency identification signaling. Science, this issue p. 780; see also p. 754 CRISPR-associated nucleases are used to control multiscale properties of DNA-based materials. Stimuli-responsive materials activated by biological signals play an increasingly important role in biotechnology applications. We exploit the programmability of CRISPR-associated nucleases to actuate hydrogels containing DNA as a structural element or as an anchor for pendant groups. After activation by guide RNA–defined inputs, Cas12a cleaves DNA in the gels, thereby converting biological information into changes in material properties. We report four applications: (i) branched poly(ethylene glycol) hydrogels releasing DNA-anchored compounds, (ii) degradable polyacrylamide-DNA hydrogels encapsulating nanoparticles and live cells, (iii) conductive carbon-black–DNA hydrogels acting as degradable electrical fuses, and (iv) a polyacrylamide-DNA hydrogel operating as a fluidic valve with an electrical readout for remote signaling. These materials allow for a range of in vitro applications in tissue engineering, bioelectronics, and diagnostics.
Improved Iris Verification System

Most computer based systems need to be secured. Human iris is a unique identifier for each person which is used widely. Iris recognition is preferable for person verification. Iris verification divided in two phases: the enrollment phase and the testing phase. This paper tackles developing an improved iris verification system using Chinese Academy of Science Institute of Automation (CASIA) iris database. Basma Mohamed Hesham System (BMHS) consists of four main steps. These steps are: iris and pupil localization/ segmentation ,using a Canny Edge Detection scheme and circular Hough Transform with a novel dynamicbased technique in determining iris radius range ,iris normalization (using Daugman’s rubber sheet model),feature extraction/ encoding (using the convolution with log Gabor filter wavelets) ,and pattern matching (using hamming distance as a matching technique). This proposed dynamic-based technique in determining the iris radius led to improve the iris localization /segmentation level. We compared our system with other iris verification systems. BMHS is evaluated based upon False Acceptance Rate (FAR), False Rejection Rate (FRR) and computational cost required in both open and close set. A comprehensive experimental work shows an improvement in the false rejection rate and reduction in the system computational cost on different types of iris image. 1
Effect of auriculotherapy and intervention types on weight control

Abstract Background: Overweight and obesity characterized by abnormal or excessive fat accumulation, can cause many complications. Auriculotherapy, as the traditional Chinese technique, is widely applied in clinical trials for the management of body weight. The program aims to evaluate the effect and safety of auriculotherapy therapy and intervention types on weight control. Methods: All randomized controlled trials related to auriculotherapy targeting overweight and obesity will be searched in online databases, such as Medline, EMbase, Cochrane Central Register of Controlled Trials, AMED, CBM, Wanfang Data, and other databases from their inception to July 2019. The primary outcome is the difference in BMI from baseline to the end of studies. Secondary outcomes include the change of weight, percentage of body fat, waist circumference, serum lipid before and after treatment. Study selection, data extraction, and assessment of risk of bias will be performed independently by 2 reviewers. Comprehensive Meta-Analysis software (Version 3; Biostat Inc.) will be used for data synthesis. Results: This study will provide a comprehensive review of the available evidence for the treatment of obesity with auriculotherapy. Conclusion: The conclusion of this study will provide evidence to judge whether auriculotherapy is an effective therapeutic intervention for obesity. PROSPERO registration number: CRD42019136827.
Adherence to Short-course Pharmacotherapy in Adults with Irritable Bowel Syndrome

Irritable Bowel Syndrome (IBS), characterized by abdominal pain and bowel dysfunction, treatment focuses on alleviating symptoms. Adherence is crucial for pharmacologic management success. We examined 73 adult’s objective adherence to rifaximin using the taxonomy for adherence. Demographic, quality of life (QOL), psychological distress, perceived stress, adverse childhood experiences (ACE), pain, and adherence data were collected. Impaired QOL, elevated psychological distress and perceived stress, and a significant number of ACE were reported at baseline. Average time to prescription initiation was 2.5 days. Once implemented, 92% missed midday dose and persisted 5 days beyond the prescribed dose. High-adherers reported lower pain levels post-rifaximin compared to low-adherers. Objective adherence was significantly lower than self-reported. Objective adherence was not predicted by above variables. Adherence to rifaximin is poor in those with IBS. Future research examining perceived barriers/facilitators toward rifaximin adherence may provide insight into patient-centered, modifiable targets for adherence interventions and improve patient-related outcomes.
Hyperspectral anomaly detection based on stacked denoising autoencoders

Abstract. Hyperspectral anomaly detection (AD) is an important technique of unsupervised target detection and has significance in real situations. Due to the high dimensionality of hyperspectral data, AD will be influenced by noise, nonlinear correlation of band, or other factors that lead to the decline of detection accuracy. To overcome this problem, a method of hyperspectral AD based on stacked denoising autoencoders (AE) (HADSDA) is proposed. Simultaneously, two different feature detection models, spectral feature (SF) and fused feature by clustering (FFC), are constructed to verify the effectiveness of the proposed algorithm. The SF detection model uses the SF of each pixel. The FFC detection model uses a similar set of pixels constructed by clustering and then fuses the set of pixels by the stacked denoising autoencoders algorithm (SDA). The SDA is an algorithm that can automatically learn nonlinear deep features of the image. Compared with other linear or nonlinear feature extraction methods, the detection result of the proposed algorithm is greatly improved. Experiment results show that the proposed algorithm is an excellent feature learning method and can achieve higher detection performance.
Generating a Health Information Technology Event Database from FDA MAUDE Reports

Patient safety events (PSEs), or medical errors, are major impediments to healthcare system safety. Health information technology (HIT) is expected to promote quality of care. Nonetheless, HIT also creates unintended consequences that concern patient safety consolidating a high-quality database of HIT events is essential to understanding their nature. Previous studies demonstrated the potential to use FDA Manufacturer and User Facility Device Experience (MAUDE) database to extract HIT events. In this study, we utilized classic and CNN models to extract HIT events from MAUDE. Both individual and combined models were evaluated on the test set, where the best model identified HIT events with ~90% accuracy and achieved a ~. 87 f1 score. This model was capable of identifying HIT events in an HIT-exclusive database and serving as a quality and error check tool during event reporting. Moreover, the strategy of HIT event identification may scale in developing other PSE subtype-specific databases.
Protein aggregation and mitigation strategy in low pH viral inactivation for monoclonal antibody purification

ABSTRACT Significant amounts of soluble product aggregates were observed during low-pH viral inactivation (VI) scale-up for an IgG4 monoclonal antibody (mAb IgG4-N1), while small-scale experiments in the same condition showed negligible aggregation. Poor mixing and product exposure to low pH were identified as the root cause. To gain a mechanistic understanding of the problem, protein aggregation properties were studied by varying critical parameters including pH, hold time and protein concentration. Comprehensive biophysical characterization of product monomers and aggregates was performed using fluorescence-size-exclusion chromatography, differential scanning fluorimetry, fluorescence spectroscopy, and dynamic light scattering. Results showed IgG4-N1 partially unfolds at about pH 3.3 where the product molecules still exist largely as monomers owing to strong inter-molecular repulsions and favorable colloidal stability. In the subsequent neutralization step, however, the conformationally changed monomers are prone to aggregation due to weaker inter-molecular repulsions following the pH transition from 3.3 to 5.5. Surface charge calculations using homology modeling suggested that intra-molecular repulsions, especially between CH2 domains, may contribute to the IgG4-N1 unfolding at ≤ pH 3.3. Computational fluid dynamics (CFD) modeling was employed to simulate the conditions of pH titration to reduce the risk of aggregate formation. The low-pH zones during acid addition were characterized using CFD modeling and correlated to the condition causing severe product aggregation. The CFD tool integrated with the mAb solution properties was used to optimize the VI operating parameters for successful scale-up demonstration. Our research revealed the governing aggregation mechanism for IgG4-N1 under acidic conditions by linking its molecular properties and various process-related parameters to macroscopic aggregation phenomena. This study also provides useful insights into the cause and mitigation of low-pH-induced IgG4 aggregation in downstream VI operation.
From Target to Drug: Generative Modeling for Multimodal Structure-Based Ligand Design.

Chemical space is impractically large and conventional structure-based virtual screening techniques cannot be used to simply search through the entire space to discover effective bioactive molecules. To address this shortcoming we propose a generative adversarial network to generate, rather than search, diverse three-dimensional ligand shapes complementary to the pocket. Furthermore, we show that the generated molecule shapes can be decoded using a shape-captioning network into a sequence of SMILES enabling directly structure-based de novo drug design. We evaluate the quality of the method by both structure- (Docking) and ligand-based (QSAR) virtual screening methods. For both evaluation approaches we observed enrichment compared to random sampling from initial chemical space of ZINC drug-like compounds.
Patient-Pivoted Automated Trial Eligibility Pipeline: The First of Three Phases in a Modular Architecture

Automated extraction of patient trial eligibility for clinical research studies can increase enrollment at a decreased time and money cost. We have developed a modular trial eligibility pipeline including patient-batched processing and an internal webservice backed by a uimaFIT pipeline as part of a multi-phase approach to include note-batched processing, the ability to query trials matching patients or patients matching trials, and an external alignment engine to connect patients to trials.
Superparamagnetic iron oxide nanoparticles (SPIONs) modulate hERG ion channel activity

Abstract Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used in various biomedical applications, such as diagnostic agents in magnetic resonance imaging (MRI), for drug delivery vehicles and in hyperthermia treatment of tumors. Although the potential benefits of SPIONs are considerable, there is a distinct need to identify any potential cellular damage associated with their use. Since human ether à go-go-related gene (hERG) channel, a protein involved in the repolarization phase of cardiac action potential, is considered one of the main targets in the drug discovery process, we decided to evaluate the effects of SPIONs on hERG channel activity and to determine whether the oxidation state, the dimensions and the coating of nanoparticles (NPs) can influence the interaction with hERG channel. Using patch clamp recordings, we found that SPIONs inhibit hERG current and this effect depends on the coating of NPs. In particular, SPIONs with covalent coating aminopropylphosphonic acid (APPA) have a milder effect on hERG activity. We observed that the time-course of hERG channel modulation by SPIONs is biphasic, with a transient increase (∼20% of the amplitude) occurring within the first 1–3 min of perfusion of NPs, followed by a slower inhibition. Moreover, in the presence of SPIONs, deactivation kinetics accelerated and the activation and inactivation I–V curves were right-shifted, similarly to the effect described for the binding of other divalent metal ions (e.g. Cd2+ and Zn2+). Finally, our data show that a bigger size and the complete oxidation of SPIONs can significantly decrease hERG channel inhibition. Taken together, these results support the view that Fe2+ ions released from magnetite NPs may represent a cardiac risk factor, since they alter hERG gating and these alterations could compromise the cardiac action potential.
Neurocognitive profile of outpatients with unipolar depressive disorders

ABSTRACT Introduction: It is widely accepted that major depressive disorder (MDD) is associated with impairments in several cognitive domains in inpatients, but cognitive functioning has barely been systematically investigated in depressed outpatients. The aims of the present study were to examine cognitive functioning in depressed outpatients in comparison with healthy controls and to determine whether cognitive deficits vary as a function of different disorder characteristics and demographic variables. Method: We compared 103 outpatients with recurrent MDD in an acute phase of the illness with 103 healthy controls matched on age, gender, and education level using a neuropsychological battery covering the domains of processing speed, attention, memory, working memory, and executive functions. Results: Depressed outpatients were found to be impaired in all five assessed cognitive domains. These impairments varied as a function of the disorder characteristics, particularly severity of depression, intake of medication, age of depression onset, duration of current episode, and rumination as a psychological variable as well as age, premorbid intelligence, and education level as demographic variables. Conclusions: In the present study we tried to systematically investigate the impact of different disorder characteristics and demographic variables on the cognitive dysfunction of outpatients with MDD. The results indicate a moderate to severe cognitive impairment of outpatients with MDD and reveal an influence of different disease characteristics as well as demographics. These cognitive impairments may affect the course of the disease and should be considered in outpatient therapy.
Phase I Trial of Well-Differentiated Neuroendocrine Tumors (NETs) with Radiolabeled Somatostatin Antagonist 177Lu-Satoreotide Tetraxetan

Purpose: Radiolabeled somatostatin receptor 2 (SSTR2) antagonists have shown higher tumor uptake and tumor-to-organ ratios than somatostatin agonists in preclinical models of neuroendocrine tumors (NETs). We performed a phase I study to evaluate the safety and efficacy of SSTR2 antagonist 177Lu-satoreotide tetraxetan. Patients and Methods: Twenty patients with advanced SSTR2-positive NETs were treated with 177Lu-satoreotide tetraxetan. Patients first underwent a dosimetry study with 177Lu-satoreotide tetraxetan to determine the therapeutic activity that could be safely administered. This activity was split into two equal cycles to be delivered 3 months apart. The maximum activity was 7.4 GBq per cycle. Results: Of 20 patients with NETs (one lung, seven small bowel, nine pancreatic, one gastric, one rectal, one kidney; mean prior treatments: three), six received one cycle of 177Lu- satoreotide tetraxetan and 14 received two cycles. Hematologic toxicity after cycle 1 was mild-moderate and reversed before cycle 2. However, grade 4 hematologic toxicity occurred in four of seven (57%) patients after cycle 2 of 177Lu-satoreotide tetraxetan. The study was suspended, and the protocol modified to limit the cumulative absorbed bone marrow dose to 1 Gy and to reduce prescribed activity for cycle 2 by 50%. The best overall response rate was 45% [5% complete response (1/20), 40% partial response (8/20)]; with 40% stable disease (8/20) and 15% progression of disease (3/20). Median progression-free survival (PFS) was 21.0 months (95% CI, 13.6–NR). Conclusions: In this trial of heavily treated NETs, preliminary data are promising for the use of 177Lu-satoreotide tetraxetan. Additional studies are ongoing to determine optimal therapeutic dose/schedule.
How to Assess Success of HIT Project Management: An Example of the Use of the Common Assessment Framework (CAF)

The purpose of this study was to assess the project management of a national health information technology project focused on developing digital health care services. An e-questionnaire was sent at the end of the development project, and 93 experts (18%) from five university hospitals responded. The questionnaire was based on the Common Assessment Framework (CAF) to identify management success and also to get an overview of the project's performance. The questionnaire contained 11 background variables and 17 Likert scale items in five themes on leadership, strategy and planning, people, partnerships and resources, and processes, and one open-ended question. After analysis using descriptive statistical methods, the results showed that, overall, participants felt confident about management of the project. Criticism focused on the distribution of resources and lack of knowledge about the status of development activities in other hospitals. The CAF enablers criteria revealed subjects for further development.
A Method to Accelerate and Visualize Iterative Clinical Paper Searching

Clinical paper searching is a major task for clinical researchers to collect authoritative and up-to-date evidences to support their research works and clinical practices. Currently, this task needs huge amount of labor work. Researchers usually spend a lot of time searching on the online repository and iterating many times to get the final paper list. Systematic review is a special case, in which the paper searching process is a critical step. To address this challenge, this paper introduces a method to streamline the iterative paper searching process. It automatically selects the most probably matched papers, and then generates new search strategy. All the intermediate results are visualized based on the paper citation graph. It assembles technologies such as PageRank and Topic-based clustering to accelerate the paper searching tasks. The precision, recall, and execution time of the proposed method are then evaluated by comparing with published systematic reviews.
Dialogue Analysis for Clinical Data Query Mediation

Efficient access to clinical data by investigators is critical for data-driven biomedical research. Mediated query is commonly adopted to facilitate data access for investigators. However, the query mediation process remains a black-box. This study analyzed the email-based dialogues between investigators and clinical data query mediators from three institutions. We identify discussion topics and their frequencies, model task flows, and analyze user needs for query mediation support revealed from the dialogues. While the datasets between different institutions are distinct in some notable respects, we find that together they provide common insights for streamlining data access. From our findings, we conclude an intelligent dialogue-based query support model is feasible to automate human-mediated clinical data access for investigators and stakeholders.