Miracle-dz/UniFAR-FTUs huggingface dataset:
miR-363 confers taxane resistance in ovarian cancer by targeting the Hippo pathway member, LATS2

Ovarian cancer is the most aggressive female reproductive tract tumours. Taxane (paclitaxel; TX) is widely used for ovarian cancer treatment. However, ovarian cancers often acquire chemoresistance. MicroRNAs (miR) have been reported to mediate many tumours’chemoresistance. We investigated the role of miR-363 in the chemoresistance of the ovarian cancer cell line, KF, and its TX-resistant derivative (KF-TX) cells. QRT-PCR indicated that miR-363 was upregulated in KF-TX cells, and introduction of miR-363 into sensitive ovarian cancer cells confers TX-resistance and significantly inhibited the expression of the Hippo member, LATS2, as indicated by viability, clonogenic assay and expression analysis. Furthermore, we validated the role of LATS2 in TX-response by sh-based silencing, which also confers TX-resistance to the ovarian cancer cells. On the other hand, specific inhibitor against miR-363 restored the response to TX in the resistant cells. In addition, miR-363 was found to bind to the 3′-UTR of LATS2 mRNA, confirming that miR-363 directly targets LATS2 as indicated by dual luciferase assay. RT-PCR-based evaluation of miR-363 in a panel of human ovarian tumours revealed its upregulation in most of the tumour tissues identified as resistant while it was downregulated in most of the tissues identified as sensitive ones. Moreover, higher levels of miR-363 in human ovarian cancer specimens were significantly correlated with TX chemoresistance. Taken together, our study reveals the involvement of miR-363 in chemoresistance by targeting LATS2 in ovarian cancers, raising the possibility that combination therapy with a miR-363 inhibitor and TX may increase TX efficacy and reduce the chance of TX-resistance.
Practical guide for identifying unmet clinical needs for biomarkers

The development and evaluation of novel biomarkers and testing strategies requires a close examination of existing clinical pathways, including mapping of current pathways and identifying areas of unmet need. This approach enables early recognition of analytical and clinical performance criteria to guide evaluation studies, in a cyclical and iterative manner, all the time keeping the clinical pathway and patient health outcomes as the key drivers in the process. The Test Evaluation Working Group of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM TE-WG) https://www.eflm. eu/site/page/a/1158 has published a conceptual framework of the test evaluation cycle which is driven by the clinical pathway, inherent to which is the test purpose and role within the pathway that are defined by clinical need. To supplement this framework, the EFLM TE-WG has also published an interactive checklist for identifying unmet clinical needs for new biomarkers; a practical tool that laboratories, clinicians, researchers and industry can equally use in a consistent manner when new tests are developed and before they are released to the market. It is hoped that these practical tools will provide consistent and appropriate terminology in this diverse field and offer a platform that facilitates greater consultation and collaboration between all stakeholders. The checklist should assist the work of all colleagues involved in the discovery of novel biomarkers and implementation of new medical tests. The tool is aligned with the IOM recommendations and the FDA and CE regulating body’s requirements.
A bimodal theranostic nanodelivery system based on [graphene oxide-chlorogenic acid-gadolinium/gold] nanoparticles

We have synthesized a bimodal theranostic nanodelivery system (BIT) that is based on graphene oxide (GO) and composed of a natural chemotherapeutic agent, chlorogenic acid (CA) used as the anticancer agent, while gadolinium (Gd) and gold nanoparticles (AuNPs) were used as contrast agents for magnetic resonance imaging (MRI) modality. The CA and Gd guest agents were simultaneously loaded on the GO nanolayers using chemical interactions, such as hydrogen bonding and π–π non-covalent interactions to form GOGCA nanocomposite. Subsequently, the AuNPs were doped on the surface of the GOGCA by means of electrostatic interactions, which resulted in the BIT. The physico–chemical studies of the BIT affirmed its successful development. The X-ray diffractograms (XRD) collected of the various stages of BIT synthesis showed the successive development of the hybrid system, while 90% of the chlorogenic acid was released in phosphate buffer solution (PBS) at pH 4.8. This was further reaffirmed by the in vitro evaluations, which showed stunted HepG2 cancer cells growth against the above 90% cell growth in the control cells. A reverse case was recorded for the 3T3 normal cells. Further, the acquired T1-weighted image of the BIT doped samples obtained from the MRI indicated contrast enhancement in comparison with the plain Gd and water references. The abovementioned results portray our BIT as a promising future chemotherapeutic for anticancer treatment with diagnostic modalities.
The effect of a fibrin sealant on knee function after total knee replacement surgery. Results from the FIRST trial. A multicenter randomized controlled trial

Background Total knee replacement (TKR) is increasingly performed in short term hospital stay, making same day mobilization an important issue is after surgery. This implies little joint effusion by reducing intra-articular blood loss, which will enhance knee range of motion. The application of a topical fibrin sealant on the intraoperative bare bone and synovial tissue may contribute to better early full mobilization and thus improved functional outcomes. Since ambulation with a fully extended knee is less strenuous, we hypothesized that patients who received fibrin sealant would demonstrate improved early knee extension after six weeks compared to patients who received standard care. Methods A multicenter randomized controlled trial in a consecutive series of osteoarthritis patients scheduled for TKR surgery. Participants were randomized to receive fibrin sealant or not before closing the knee joint capsule. Primary outcome was change in knee extension angle(°) at short term (2 weeks) follow-up (cExt). Secondary outcomes were 6-week extension angle, knee flexion angle, hemoglobin loss, blood transfusion rates, complication rates, the Knee Society Score, and the KOOS and EQ5D questionnaires. Results When data on primary outcome became available from 250 patients, an interim analysis was performed by an independent Data Safety Monitoring Board for safety and effectivity assessment. This analysis showed that sufficient patients were included to detect a cExt of 10° between both groups. Inclusion was stopped however, all in the meantime included patients were treated according to their randomization. A total of 466 were available for analysis. Both groups were comparable in terms of baseline characteristics. The estimated mean cExt difference was 0.2° (95%CI -0.5 to 0.9). No differences in secondary outcomes were found. Conclusions No beneficial effects or side effects were found of a topically applied fibrin sealant during TKR surgery. These results discourage the clinical use of a fibrin sealant in TKR. Trial registration Dutch Trial Register, NTR2500.
A 2-D Ultrasound Transducer With Front-End ASIC and Low Cable Count for 3-D Forward-Looking Intravascular Imaging: Performance and Characterization

Intravascular ultrasound (IVUS) is an imaging modality used to visualize atherosclerosis from within the inner lumen of human arteries. Complex lesions like chronic total occlusions require forward-looking IVUS (FL-IVUS), instead of the conventional side-looking geometry. Volumetric imaging can be achieved with 2-D array transducers, which present major challenges in reducing cable count and device integration. In this work, we present an 80-element lead zirconium titanate matrix ultrasound transducer for FL-IVUS imaging with a front-end application-specific integrated circuit (ASIC) requiring only four cables. After investigating optimal transducer designs, we fabricated the matrix transducer consisting of 16 transmit (TX) and 64 receive (RX) elements arranged on top of an ASIC having an outer diameter of 1.5 mm and a central hole of 0.5 mm for a guidewire. We modeled the transducer using finite-element analysis and compared the simulation results to the values obtained through acoustic measurements. The TX elements showed uniform behavior with a center frequency of 14 MHz, a −3-dB bandwidth of 44%, and a transmit sensitivity of 0.4 kPa/V at 6 mm. The RX elements showed center frequency and bandwidth similar to the TX elements, with an estimated receive sensitivity of $3.7~\mu \text{V}$ /Pa. We successfully acquired a 3-D FL image of three spherical reflectors in water using delay-and-sum beamforming and the coherence factor method. Full synthetic-aperture acquisition can be achieved with frame rates on the order of 100 Hz. The acoustic characterization and the initial imaging results show the potential of the proposed transducer to achieve 3-D FL-IVUS imaging.
Electromagnetic Brain Source Imaging by Means of a Robust Minimum Variance Beamformer

Objective: Adaptive beamformer methods that have been extensively used for functional brain imaging using EEG/MEG (magnetoencephalography) signals are sensitive to model mismatches. We propose a robust minimum variance beamformer (RMVB) technique, which explicitly incorporates the uncertainty of the lead field matrix into the estimation of spatial-filter weights that are subsequently used to perform the imaging. Methods: The uncertainty of the lead field is modeled by ellipsoids in the RMVB method; these hyperellipsoids (ellipsoids in higher dimensions) define regions of uncertainty for a given nominal lead field vector. These ellipsoids are estimated empirically by sampling lead field vectors surrounding each point of the source space, or more generally by building several forward models for the source space. Once these uncertainty regions (ellipsoids) are estimated, they are used to perform the source-imaging task. Computer simulations are conducted to evaluate the performance of the proposed RMVB technique. Results: Our results show that robust beamformers can outperform conventional beamformers in terms of localization error, recovering source dynamics, and estimation of the underlying source extents when uncertainty in the lead field matrix is properly determined and modeled. Conclusion: The RMVB can be substituted for conventional beamformers, especially in applications where source imaging is performed off-line, and computational speed and complexity are not of major concern. Significance: A high-quality source imaging can be utilized in various applications, such as determining the epileptogenic zone in medically intractable epilepsy patients or estimating the time course of activity, which is a required step for computing the functional connectivity of brain networks.
Cervical Spine Dysfunction Following Pediatric Sports-Related Head Trauma

Objective: To examine the prevalence of cervical spine injuries among children and adolescents referred with suspected and diagnosed sports-related concussion (SRC); and evaluate the effect of cervical spine dysfunction (CSD) on physician-documented clinical recovery following SRC. Setting: A multidisciplinary pediatric concussion program. Participants: A total of 266 patients (6-19 years) referred with suspected SRC. Design: A retrospective cohort study. Main Measures: CSD defined as neurological symptoms localized to the cervical spine or the presence of neck pain, headache, or dizziness and abnormal cervical spine examination findings; physician-documented clinical recovery. Results: One patient was diagnosed with a T1 compression fracture. Of the 246 patients diagnosed with SRC, 80 (32.5%) met the clinical criteria for CSD including 4 patients with central cord neuropraxia and 1 with a spinal cord injury without radiographic abnormality (SCIWORA). Excluding patients with central cord neuropraxia OR SCIWORA, patients with SRC with CSD took longer to achieve physician-documented clinical recovery (28.5 days vs 17 days, P < .0001) and were 3.95 times more likely to experience delayed physician-documented clinical recovery (>4 weeks postinjury) compared with those without CSD. Conclusions: Patients with suspected and diagnosed SRC can present with a wide spectrum of coincident cervical spine injuries. Cervical spine dysfunction may be a risk factor for delayed clinical recovery.
Directory Reconciliation

We initiate the theoretical study of directory reconciliation, a generalization of document exchange, in which Alice and Bob each have different versions of a set of documents that they wish to synchronize. This problem is designed to capture the setting of synchronizing different versions of file directories, while allowing for changes of file names and locations without significant expense. We present protocols for efficiently solving directory reconciliation based on a reduction to document exchange under edit distance with block moves, as well as protocols combining techniques for reconciling sets of sets with document exchange protocols. Along the way, we develop a new protocol for document exchange under edit distance with block moves inspired by noisy binary search in graphs, which uses only $O(k \log n)$ bits of communication at the expense of $O(k \log n)$ rounds of communication.
The Relationship Between Sociodemographic Variables and Depressive Symptoms in Uncomplicated Pregnant Women at Term

The aim of this study was to investigate the relationship between sociodemographic variables and depressive symptoms in uncomplicated pregnant women at term. Four hundred-seventeen pregnant patients at term who attended to antenatal outpatient clinic without significant risk factors were recruited for the application of questionnaire survey, and Beck Depression Inventory (BDI). The cut-off point of the scale was evaluated as 17. Accordingly, the patients with BDI scores between 0 and 16 were classified in Group 1, while the other patients were categorized in Group 2. Educational level, occupation, husband’s occupation, habitat, social security status, level of financial income, previous psychiatric illness in her or anyone in her family, smoking status, difficulty in arrival to a health center, family structure, migration status, social support provided from her family and close environment, the number of her marriages, the status of planned or unplanned pregnancy, the outcome of previous pregnancy, the use of vitamin pills in pregnancy, conceiving with a medical treatment (except in vitro fertilization), and number of parities were not significantly different between groups. The presence of anxiety for fetal health, unfavorable life experience, marital problems, history of premenstrual syndrome, the lower birth weights, and the absence of a civil marriage and regular antenatal visits in Group 2 were significantly more frequent than Group 1. As a conclusion; many individual variables of uncomplicated pregnants at term can induce the development of depressive symptoms. The early recognition of the risk factors that aggravate depressive mood of the pregnants may aid in taking measures aiming to improve maternal and neonatal heath state.
A balanced-to-balanced filtering gysel power divider with unequal power division

A balanced-to-balanced Gysel power divider is proposed with bandpass filtering response and unequal power division. Design equations are provided for the proposed component, according to the power division ratio and filter specifications. Large design flexibility, small circuit size and low insertion loss can be achieved simultaneously. A microstrip prototype is developed at f0=2 GHz with a second-order Chebyshev bandpass response. The bandwidth is 8% and the power division ratio of differential-mode outputs is 1:3. The phase difference is smaller than 5°. The suppression of in-band common-mode transmission and mode conversion is over 25 dB. Our idea is validated by the good agreement obtained between the measured and simulated results.
Epilogue to the special issue on the use of mobile technology for real-time assessment and treatment of substance use disorders

The current issue of the American Journal of Drug and Alcohol Abuse focuses primarily on the use of mobile technology for real-time assessment of variables relevant to substance use disorders. The articles within characterize predictors of substance use based on data collected in the relevant moment, rather than in retro-spect. When ecological momentary assessment (EMA) methods are employed optimally, the timing of variables, such as affect and craving, in relation to substance use can be characterized. There is also the potential to identify bidirectional relationships between variables of interest (e.g., negative affect → relapse → negative affect) and to distinguish within-person versus between-person effects. EMA methods offer the potential for a more detailed understanding of the factors that maintain substance use or lead to relapse among those receiving treatment. Most of the studies in this special issue used EMA to identify predictors of craving, affect, and/or substance use (1 – 6). The studies focus on opioid (1,6), cigarette (4,7), marijuana (2), alcohol use (3), and general substance use (5). The articles also touch upon other issues related to substance abuse including homelessness (5), pain (4), trauma exposure (2), and post-traumatic stress disorder (PTSD, 3).
Deletion of the miR172 target site in a TOE-type gene is a strong candidate variant for dominant double-flower trait in Rosaceae.

Double flowers with supernumerary petals have been selected by humans for their attractive appearance and commercial value in several ornamental plants, including Prunus persica (peach), a recognized model for Rosaceae genetics and genomics. Despite the relevance of this trait, knowledge of the underlying genes is limited. Of two distinct loci controlling the double-flower phenotype in peach, we focused on the dominant Di2 locus. High-resolution linkage mapping in five segregating progenies delimited Di2 to an interval spanning 150 858 bp and 22 genes, including Prupe.6G242400 encoding an euAP2 transcription factor. Analyzing genomic resequencing data from single- and double-flower accessions, we identified a deletion spanning the binding site for miR172 in Prupe.6G242400 as a candidate variant for the double-flower trait, and we showed transcript expression for both wild-type and deleted alleles. Consistent with the proposed role in controlling petal number, Prupe.6G242400 is expressed in buds at critical times for floral development. The indelDi2 molecular marker designed on this sequence variant co-segregated with the phenotype in 621 progenies, accounting for the dominant inheritance of the Di2 locus. Further corroborating the results in peach, we identified a distinct but similar mutation in the ortholog of Prupe.6G242400 in double-flower roses. Phylogenetic analysis showed that these two genes belong to a TARGET OF EAT (TOE)-type clade not represented in Arabidopsis, indicating a divergence of gene functions between AP2-type and TOE-type factors in Arabidopsis and other species. The identification of orthologous candidate genes for the double-flower phenotype in two important Rosaceae species provides valuable information to understand the genetic control of this trait in other major ornamental plants.
Acute neurology simulation training

Acute neurology is the neurological care that a patient receives in an emergency or urgent care situation. This can be adapted successfully to training in a simulation where learners are immersed in realistic scenarios in a safe, controlled and reproducible environment. In addition to teaching important technical skills that improve knowledge of the diagnosis and management of acute neurology, the simulation laboratory provides a valuable setting to improve human factors and non-technical skills, such as teamwork and leadership. Simulations are best conducted in a multiprofessional group with scenarios that allow different team members (nurses, physician associates, core medical and specialist trainees) to participate in their actual role. These training sessions require clear learning objectives, and involve designing the scenarios, running the session and ending with a structured debriefing to consolidate learning. The ultimate aim is to improve the team’s effectiveness to deliver safe acute neurological care in the emergency department and on the wards.
Discriminative Feature Selection via Employing Smooth and Robust Hinge Loss

A wide variety of sparsity-inducing feature selection methods have been developed in recent years. Most of the loss functions of these approaches are built upon regression since it is general and easy to optimize, but regression is not well suitable for classification. In contrast, the hinge loss (HL) of support vector machines has proved to be powerful to handle classification tasks, but a model with existing multiclass HL and sparsity regularization is difficult to optimize. In view of that, we propose a new loss, called smooth and robust HL, which gathers the merits of regression and HL but overcome their drawbacks, and apply it to our sparsity regularized feature selection model. To optimize the model, we present a new variant of accelerated proximal gradient (APG) algorithm, which boosts the discriminative margins among different classes, compared with standard APG algorithms. We further propose an efficient optimization technique to solve the proximal projection problem at each iteration step, which is a key component of the new APG algorithm. We theoretically prove that the new APG algorithm converges at rate $O({1}/{k^{2}})$ if it is convex ( $k$ is the iteration counter), which is the optimal convergence rate for smooth problems. Experimental results on nine publicly available data sets demonstrate the effectiveness of our method.
Detection and Discrimination Thresholds for Haptic Gratings on Electrostatic Tactile Displays

Designing algorithmsfor rendering haptic texture on electrostatic tactile displays requires a quantitative understanding of human perception. In this paper, we report detection and discrimination thresholds for haptic gratings rendered on such displays based on the waveform and amplitude of the applied voltage. The haptic gratings consist of functions that describe the variation in voltage amplitude as a function of the position of finger on the display. Four types of virtual haptic gratings are considered in two experiments. In Experiment I, we estimate the absolute detection thresholds of haptic gratings for four different voltage amplitude functions, consisting of spatial waveforms with sinusoidal, square, triangle, or sawtooth shape. In Experiment II, we report discrimination thresholds for haptic gratings at five reference values of the voltage amplitude (80, 120, 160, 200, and 240 Vpp) for each of the voltage amplitude functions used in Experiment I. The results indicate that the detection thresholds for the four virtual haptic gratings are between 30 and 36 Vpp, and that the JND increases with the increase of voltage amplitudes. In addition, the JNDs of the four virtual gratings differ significantly, with the lowest and highest values being given by the triangle and sawtooth waveform, respectively.