Miracle-dz/UniFAR-FTUs huggingface dataset:
Legal & ethical compliance when sharing biospecimen

Abstract When obtaining samples from biobanks, resolving ethical and legal concerns is a time-consuming task where researchers need to balance the needs of privacy, trust and scientific progress. The Biobanking and Biomolecular Resources Research Infrastructure-Large Prospective Cohorts project has resolved numerous such issues through intense communication between involved researchers and experts in its mission to unite large prospective study sets in Europe. To facilitate efficient communication, it is useful for nonexperts to have an at least basic understanding of the regulatory system for managing biological samples. Laws regulating research oversight are based on national law and normally share core principles founded on international charters. In interview studies among donors, chief concerns are privacy, efficient sample utilization and access to information generated from their samples. Despite a lack of clear evidence regarding which concern takes precedence, scientific as well as public discourse has largely focused on privacy concerns and the right of donors to control the usage of their samples. It is therefore important to proactively deal with ethical and legal issues to avoid complications that delay or prevent samples from being accessed. To help biobank professionals avoid making unnecessary mistakes, we have developed this basic primer covering the relationship between ethics and law, the concept of informed consent and considerations for returning findings to donors.
Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation

There is now a large body of data indicating that the cannabinoid receptor type 2 (CB2) is linked to a variety of immune events. This functional relevance appears to be most salient in the course of inflammation, a process during which there is an increased number of receptors that are available for activation. Studies aimed at elucidating signal transduction events resulting from CB2 interaction with its native ligands, and of the role of exogenous cannabinoids in modulating this process, are providing novel insights into the role of CB2 in maintaining a homeostatic immune balance within the host. Furthermore, these studies suggest that the CB2 may serve as a selective molecular target for therapeutic manipulation of untoward immune responses, including those associated with a variety of neuropathies that exhibit a hyperinflammatory component.
Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies

ABSTRACT Human papillomavirus (HPV) is widely known as a cause of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e. E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their peculiarities, these oncogenes represent an excellent target for cancer immunotherapy. In this work the authors highlight the potential use of therapeutic vaccines as safe and effective pharmacological tools in cervical disease, focusing on vaccines that have reached the clinical trial phase. Many therapeutic HPV vaccines have been tested in clinical trials with promising results. Adoptive T-cell therapy showed clinical activity in a phase II trial involving advanced CC patients. A phase II randomized trial showed clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN. Several trials involving peptide-protein-based vaccines and live-vector based vaccines demonstrated that these approaches are effective in CIN as well as in advanced CC patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease. The synergic combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, immunomodulators or immune checkpoint inhibitors opens a new and interesting scenario in this disease.
Specifying Timed Patterns using Temporal Logic

Monitoring system behaviors using formal specifications appears to be an effective technique in analyzing cyber-physical systems. However, to achieve intended results in monitoring, specification languages need to be intuitive, elegant, and expressive at the first place. In this paper, we propose a metric extension of well-known Halpern-Shoham (hs) logic, called Metric Compass Logic (mcl), for monitoring purposes. Originally proposed for high-level temporal reasoning, the logic hs is very expressive and enables users to specify many temporal patterns in an intuitive and elegant way. As our main contribution, we present an offline monitoring technique for timed patterns specified in mcl. Our solution is built upon the framework developed for timed regular expressions (TRE) matching but explores a different (logical) direction. We finally study several practical features concerning atomic formulas and discuss a combined timed pattern speciication language with TRE.
Simple shearing of soft biological tissues

Shearing is induced in soft tissues in numerous physiological settings. The limited experimental data available suggest that a severe strain-stiffening effect occurs in the shear stress when soft biological tissues are subjected to simple shear in certain directions. This occurs at relatively small amounts of shear (when compared with the simple shear of rubbers). This effect is modelled within the framework of nonlinear elasticity by consideration of a class of incompressible anisotropic materials. Owing to the large stresses generated for relatively small amounts of shear, particular care must be exercised in order to maintain a homogeneous deformation state in the bulk of the specimen. The results obtained are relevant to the development of accurate shear test protocols for the determination of constitutive properties of soft tissues. It is also demonstrated that there is a fundamental ambiguity in determining the normal stresses in simple shear when soft tissues are modelled as incompressible hyperelastic materials owing to the arbitrary nature of the hydrostatic pressure term. Two physically well-motivated approaches to determining the pressure are presented here, and the resulting hydrostatic stresses are compared and contrasted. The possible generation of cavitational damage owing to critical hydrostatic stress levels is briefly discussed.
Stromal interaction molecule 1 regulates growth, cell cycle, and apoptosis of human tongue squamous carcinoma cells

Oral tongue squamous cell carcinoma (OTSCC) is the most common type of oral carcinomas. However, the molecular mechanism by which OTSCC developed is not fully identified. Stromal interaction molecule 1 (STIM1) is a transmembrane protein, mainly located in the endoplasmic reticulum (ER). STIM1 is involved in several types of cancers. Here, we report that STIM1 contributes to the development of human OTSCC. We knocked down STIM1 in OTSCC cell line Tca-8113 with lentivirus-mediated shRNA and found that STIM1 knockdown repressed the proliferation of Tca-8113 cells. In addition, we also showed that STIM1 deficiency reduced colony number of Tca-8113 cells. Knockdown of STIM1 repressed cells to enter M phase of cell cycle and induced cellular apoptosis. Furthermore, we performed microarray and bioinformatics analysis and found that STIM1 was associated with p53 and MAPK pathways, which may contribute to the effects of STIM1 on cell growth, cell cycle, and apoptosis. Finally, we confirmed that STIM1 controlled the expression of MDM2, cyclin-dependent kinase 4 (CDK4), and growth arrest and DNA damage inducible α (GADD45A) in OTSCC cells. In conclusion, we provide evidence that STIM1 contributes to the development of OTSCC partially through regulating p53 and MAPK pathways to promote cell cycle and survival.
How physical therapists instruct patients with stroke: an observational study on attentional focus during gait rehabilitation after stroke

Abstract Purpose: People without neurological impairments show superior motor learning when they focus on movement effects (external focus) rather than on movement execution itself (internal focus). Despite its potential for neurorehabilitation, it remains unclear to what extent external focus strategies are currently incorporated in rehabilitation post-stroke. Therefore, we observed how physical therapists use attentional focus when treating gait of rehabilitating patients with stroke. Methods: Twenty physical therapist-patient couples from six rehabilitation centers participated. Per couple, one regular gait-training session was video-recorded. Therapists’ statements were classified using a standardized scoring method to determine the relative proportion of internally and externally focused instructions/feedback. Also, we explored associations between therapists’ use of external/internal focus strategies and patients’ focus preference, length of stay, mobility, and cognition. Results: Therapists’ instructions were generally more external while feedback was more internal. Therapists used relatively more externally focused statements for patients with a longer length of stay (B = −0.239, p = 0.013) and for patients who had a stronger internal focus preference (B = −0.930, p = 0.035). Conclusions: Physical therapists used more external focus instructions, but more internally focused feedback. Also, they seem to adapt their attentional focus use to patients’ focus preference and rehabilitation phase. Future research may determine how these factors influence the effectiveness of different attentional foci for motor learning post-stroke. IMPLICATIONS FOR REHABILITATION Physical therapists use a balanced mix of internal focus and external focus instructions and feedback when treating gait of stroke patients. Therapists predominantly used an external focus for patients in later rehabilitation phases, and for patients with stronger internal focus preferences, possibly in an attempt to stimulate more automatic control of movement in these patients. Future research should further explore how a patients’ focus preference and rehabilitation phase influence the effectiveness of different focus strategies. Awaiting further research, we recommend that therapists use both attentional focus strategies, and explore per patient which focus works best on a trial-and-error basis.
Bioreactors in Tissue Engineering

Tissue engineering is a promising interdisciplinary scientific field of regenerative medicine. Aiming at the structural and functional restoration of damaged tissues and organs, it possesses a role of significant socioeconomical impact. In the course towards the ultimate goal of artificially constructed natural organs, our knowledge of the elementary constitutive components of living organisms and the intrinsic mechanisms that drive their interactions is greatly enhanced. Bioreactors are valuable tools providing the technological means to investigate fundamental issues for basic research and to improve tissue‐engineering products for clinical applications. They are devices enabling the in vitro simulation of the in vivo biological, physical and mechanical environment of growing tissues. In this review paper, we discuss the general demands defining the design considerations for modern bioreactor systems. These criteria originate from physiological characteristics of the cells and biochemical and mechanical properties of the extracellular matrix (ECM). In this context, we present an overview of the various bioreactor systems dedicated to the study of specific functional tissues developed by numerous research groups.
Combined Hepatocellular-Cholangiocarcinoma

OBJECTIVE To study the cytohistologic features of combined hepatocellular-cholangiocarcinoma (CHCC-CC) in fine needle aspiration biopsy (FNAB) material. STUDY DESIGN Six hepatic FNAB cases with cell blocks (five) and hepatic resections (two) were analyzed cytohistologically and immunohistochemically. RESULTS The six cases were diagnosed as CHCC-CC based on clinicopathologic correlation. Unequivocal hepatocellular carcinoma (HCC) cells corresponding to Edmondson and Steiner's grade 3 lesions were identified in the FNAB in three instances. Adenocarcinoma, represented by cohesive columnar cells with ovoid, basal nuclei displaying nuclear palisading, acini and/or papillary structures with variable intracytoplasmic intraacinar or brush border mucin production, was identified in all cases. Intermediate cells with hybrid/polymorphic cytologic features straddling malignant hepatocytes and glandular cells were identified in five instances. Tissue alpha-fetoprotein was negative. There was brush border and/or diffuse cytoplasmic p-carcinoembryonic antigen immunoreactivity in the glandular elements. CONCLUSION FNAB diagnosis of CHCC-CC is possible if the clinical, cytohistologic and immunohistochemical findings support the presence of HCC and adenocarcinoma. Intermediate cells pose a great challenge to recognize and define: they tend to lose the classic cytologic features of malignant hepatocytes and acquire glandular characteristics. At the very least, there should be a high index of suspicion. These cases underscore the necessity for clinicopathologic correlation in enhancing the precision of FNAB diagnoses.
On-Board GNSS/IMU Assisted Feature Extraction and Matching for Oblique UAV Images

Feature extraction and matching is a crucial task in the fields of computer vision and photogrammetry. Even though wide researches have been reported, some issues are still existing for oblique images. This paper exploits the use of on-board GNSS/IMU (Global Navigation Satellite System/Inertial Measurement Unit) data to achieve efficient and reliable feature extraction and matching for oblique unmanned aerial vehicle (UAV) images. Firstly, rough POS (Positioning and Orientation System) is calculated for each image with cooperation of on-board GNSS/IMU data and camera installation angles, which enables image rectification and footprint calculation. Secondly, two robust strategies, including the geometric rectification and tile strategy, are considered to address the issues caused by perspective deformations and to relieve the side-effects of image down-sampling. According to the results of individual performance evaluation, four combinations of these two strategies are designed and comprehensively compared in BA (Bundle Adjustment) experiments by using a real oblique UAV dataset. The results reported in this paper demonstrate that the solution with the tiling strategy is superior to the other solutions in terms of efficiency, completeness and accuracy. For feature extraction and matching of oblique UAV images, it is proposed to combine the tiling strategy with existing workflows to achieve an efficient and reliable solution.
In Vitro and In Vivo Activity of IMGN853, an Antibody–Drug Conjugate Targeting Folate Receptor Alpha Linked to DM4, in Biologically Aggressive Endometrial Cancers

Grade 3 endometrioid and uterine serous carcinomas (USC) account for the vast majority of endometrial cancer deaths. The purpose of this study was to determine folic acid receptor alpha (FRα) expression in these biologically aggressive (type II) endometrial cancers and evaluate FRα as a targetable receptor for IMGN853 (mirvetuximab soravtansine). The expression of FRα was evaluated by immunohistochemistry (IHC) and flow cytometry in 90 endometrioid and USC samples. The in vitro cytotoxic activity and bystander effect were studied in primary uterine cancer cell lines expressing differential levels of FRα. In vivo antitumor efficacy of IMGN853 was evaluated in xenograft/patient-derived xenograft (PDX) models. Semiquantitative IHC analysis indicated that 41% of the USC patients overexpress FRα. Further, overexpression of FRα (i.e., 2+) was detected via flow cytometry in 22% (2/9) of primary endometrioid and in 27% (3/11) of primary USC cell lines. Increased cytotoxicity was seen with IMGN853 treatment compared with control in 2+ expressing uterine tumor cell lines. In contrast, tumor cell lines with low FRα showed no difference when exposed to IMGN853 versus control. IMGN853 induced bystander killing of FRα = 0 tumor cells. In an endometrioid xenograft model (END(K)265), harboring 2+ FRα, IMGN853 treatment showed complete resolution of tumors (P < 0.001). Treatment with IMGN853 in the USC PDX model (BIO(K)1), expressing 2+ FRα, induced twofold increase in median survival (P < 0.001). IMGN853 shows impressive antitumor activity in biologically aggressive FRα 2+ uterine cancers. These preclinical data suggest that patients with chemotherapy resistant/recurrent endometrial cancer overexpressing FRα may benefit from this treatment. Mol Cancer Ther; 17(5); 1003–11. ©2018 AACR.
Do pedometers with or without education on exercise increase functional walking capacity and physical activity level in adolescents with juvenile idiopathic arthritis?

ABSTRACT To evaluate the impact of pedometer use on the physical activity (PA) and functional walking capacity (FWC) of adolescents with juvenile idiopathic arthritis (JIA) and lower extremity (LE) involvement. Twenty-seven adolescents, aged 11–19 years with JIA and LE involvement, participated in the three-phase pedometer study that introduced the use of a pedometer and an education seminar at 6 weeks. Measurements were taken at the baseline first visit and at weeks 6, 12, and 20. The primary outcome measure was the 6-minute walk test (6MWT). Thirteen completed the study. Six-minute walk distance (6MWD) significantly increased from baseline (458.0 ± 70.8 m) to the end of phase 1 (501.4 ± 59.8 m) (p = 0.035), prior to receiving the pedometer; and from baseline to the end of study (p = 0.0037). No significant changes in 6MWD were found between weeks 6 and 12 (intervention) (p = 0.77) or between weeks 12 and 20 (follow through phase) (p = 0.27). In adolescents with LE JIA, consistent guidance and support by rheumatology professionals appears to positively influence PA and measures of FWC as seen through improved 6MWD. There was insufficient evidence to show that pedometers further increased FWC or PA.
Monoliths bearing hydrophilic surfaces for in vitro biomedical samples analysis

This contribution presents a condensed overview of strategies recently implemented to the synthesis of polymeric monoliths with well-defined surface characteristics with the aim to develop micro-sized permeable supports for flow-through separation applications in the context of life sciences. This review does not provide an exhaustive list of reported studies about the field, but it is rather intended to discuss about what caught our eyes in the literature within the last years. In this contribution, we present successively (a) what monoliths are and (b) the means to be implemented to evaluate their physico-chemical characteristics, (c) a discussion about hydrophilic and biocompatible monoliths, focusing on their preparation through both one step and multistep strategies together with their application as micro-column stationary phases for chromatography and electrochromatography. The type of separation modes expands from unique – hydrophilic interaction – to dual mixed-mode – involving a combination of h.
Fast Calculation of Protein–Protein Binding Free Energies Using Umbrella Sampling with a Coarse-Grained Model

Determination of protein–protein binding affinity values is key to understanding various underlying biological phenomena, such as how missense variations change protein–protein binding. Most existing non-rigorous (fast) and rigorous (slow) methods that rely on all-atom representation of the proteins force the user to choose between speed and accuracy. In an attempt to achieve balance between speed and accuracy, we have combined rigorous umbrella sampling molecular dynamics simulation with a coarse-grained protein model. We predicted the effect of missense variations on binding affinity by selecting three protein–protein systems and comparing results to empirical relative binding affinity values and to non-rigorous modeling approaches. We obtained significant improvement both in our ability to discern stabilizing from destabilizing missense variations and in the correlation between predicted and experimental values compared to non-rigorous approaches. Overall our results suggest that using a rigorous affinity calculation method with coarse-grained protein models could offer fast and reliable predictions of protein–protein binding free energies.
Liquid Biopsy in Clinical Management of Breast, Lung, and Colorectal Cancer

Examination of tumor molecular characteristics by liquid biopsy is likely to greatly influence personalized cancer patient management. Analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and tumor-derived exosomes, all collectively referred to as “liquid biopsies,” are not only a modality to monitor treatment efficacy, disease progression, and emerging therapy resistance mechanisms, but they also assess tumor heterogeneity and evolution in real time. We review the literature concerning the examination of ctDNA and CTC in a diagnostic setting, evaluating their prognostic, predictive, and monitoring capabilities. We discuss the advantages and limitations of various leading ctDNA/CTC analysis technologies. Finally, guided by the results of clinical trials, we discuss the readiness of cell-free DNA and CTC as routine biomarkers in the context of various common types of neoplastic disease. At this moment, one cannot conclude whether or not liquid biopsy will become a mainstay in oncology practice.
Catalytic Properties of Supported Molybdenum Oxide Catalysts: In Situ Raman and Methanol Oxidation Studies

The oxidation of methanol was studied over supported molybdenum oxide catalysts as a function of the specific oxide support (TiO2,ZrO2, Nb2O5, and A1203) and molybdenum oxide loading (surface coverage). The surface molybdenum oxide species were selective for the production of formaldehyde, and the oxide support sites yielded dimethyl ether (alumina and niobia) and methyl formate (zirconia) or were relatively inactive (titania). The turnover frequency (TOF) for the selective oxidation of methanol to formaldehyde varied by a factor of 2-4 with surface molybdenum oxide coverage and a factor of approximately 10 with the specific oxide support at monolayer coverage. The molecular structures of the surface molybdenum oxide species (isolated, tetrahedral at low coverages and polymerized, octahedralketrahedral at high coverages) did not affect the reaction selectivity but did appear to influence the slight increase in TOF with surface coverage. The order of magnitude variation in TOF with the specific oxide support correlated with the reducibility of the support and suggests that the Mo-0-support bond is critical in controlling the TOF. In situ Raman studies during methanol oxidation revealed that the supported molybdenum oxide species were 100% dispersed up to monolayer coverage. The percent reduction of the surface molybdenum oxide species, reflected by the decrease in the Raman intensity of the Mo-0 bond, during methanol oxidation was not a strong function of surface coverage and the specific oxide support. This suggests that the order of magnitude variation in the TOF with the specific oxide support is primarily related to the activity per site of the surface molybdenum oxide species rather than variation in the number of participating sites.
Transition of Bubbly to Slug Flow in a Short Vertical Channel of Gas-Liquid Two-Phase Flow

Transitions of bubbly to slug flow have been investigated for wide range of flow conditions via visualization technique. The effects of velocities of both phases were examined with variety of combinations and the experimentations were focused on the air-water flow with an industrial scale two-phase flow loop. The results show that the formations of slugs were easy with the increasing gas superficial velocity during a fixed liquid superficial velocity and were difficult when velocity of the liquid phase increases. These transitions were then evaluated using the ratio of velocities of both phases or called the slip ratio and from there a simple flow pattern map was constructed.