Miracle-dz/UniFAR-FTUs huggingface dataset:
A Series of Isatin-Hydrazones with Cytotoxic Activity and CDK2 Kinase Inhibitory Activity: A Potential Type II ATP Competitive Inhibitor

Isatin derivatives potentially act on various biological targets. In this article, a series of novel isatin-hydrazones were synthesized in excellent yields. Their cytotoxicity was tested against human breast adenocarcinoma (MCF7) and human ovary adenocarcinoma (A2780) cell lines using MTT assay. Compounds 4j (IC50 = 1.51 ± 0.09 µM) and 4k (IC50 = 3.56 ± 0.31) showed excellent activity against MCF7, whereas compound 4e showed considerable cytotoxicity against both tested cell lines, MCF7 (IC50 = 5.46 ± 0.71 µM) and A2780 (IC50 = 18.96± 2.52 µM), respectively. Structure-activity relationships (SARs) revealed that, halogen substituents at 2,6-position of the C-ring of isatin-hydrazones are the most potent derivatives. In-silico absorption, distribution, metabolism and excretion (ADME) results demonstrated recommended drug likeness properties. Compounds 4j (IC50 = 0.245 µM) and 4k (IC50 = 0.300 µM) exhibited good inhibitory activity against the cell cycle regulator CDK2 protein kinase compared to imatinib (IC50 = 0.131 µM). A molecular docking study of 4j and 4k confirmed both compounds as type II ATP competitive inhibitors that made interactions with ATP binding pocket residues, as well as lacking interactions with active state DFG motif residues.
Microbial distribution in different spatial positions within the walls of a black sulfide hydrothermal chimney

Deep-sea hydrothermal chimneys encompass diverse niches for different microbial communities with steep environmental gradients. An active sulfide hydrothermal structure was recovered from the Dudley site of the Main Endeavour Field in the Juan de Fuca Ridge. Subsamples were taken from different spatial positions within the chimney wall and analyzed for mineral composition and microbial biomass and community structure to illustrate the characteristics of microbial distribution and environmental constraints. Mineral analysis showed that the chimney was mainly composed of various Fe-, Zn-, and Cu-rich sulfides, with mineral composition and abundance varying with spatial position. Microbial populations in the chimney predominantly consisted of archaeal members affiliated with the deep-sea hydrothermal vent Euryarchaeota group, Thermococcales, and Desulfurococcales, as well as bacterial members of the Gamma-, Epsilon-, and Deltaproteobacteria. Microbial biomass and composition shifted dramatically and formed different microbial zones within the chimney walls, from predominantly mesophilic, sulfur-oxidizing bacterial communities at the outer surfaces to thermophilic or hyperthermophilic, archaeal sulfur-reducers in the inner layers of the chimney. Based on microbial physiological characteristics and their distribution profiles, we inferred that temperature, fluid geochemistry, and organic compounds probably play an important role in selecting for and sustaining microbial communities. Furthermore, in situ temperature regimes within the chimney walls were roughly estimated based on the temperatures supporting the growth of the dominant microbial groups.
Online control of reach accuracy in mice.

Reaching movements, as a basic yet complex motor behavior, are a foundational model system in neuroscience. In particular, there has been a significant recent expansion of investigation into the neural circuit mechanisms of reach behavior in mice. Nevertheless, quantification of mouse reach kinematics remains lacking, limiting comparison to the primate literature. In this study, we quantitatively demonstrate the homology of mouse reach kinematics to primate reach, and also discover novel late-phase correlational structure that implies online control. Overall, our results highlight the decelerative phase of reach as important in driving successful outcome. Specifically, we develop and implement a novel statistical machine learning algorithm to identify kinematic features associated with successful reaches and find that late-phase kinematics are most predictive of outcome, signifying online reach control as opposed to pre-planning. Moreover, we identify and characterize late-phase kinematic adjustments that are yoked to mid-flight position and velocity of the limb, allowing for dynamic correction of initial variability, with head-fixed reaches being less dependent on position in comparison to freely-behaving reaches. Furthermore, consecutive reaches exhibit positional error-correction but not hot-handedness, implying opponent regulation of motor variability. Overall, our results establish foundational mouse reach kinematics in the context of neuroscientific investigation, characterizing mouse reach production as an active process that relies on dynamic online control mechanisms.
Preparation of Multifunctional Dopamine-Coated Zerovalent Iron/Reduced Graphene Oxide for Targeted Phototheragnosis in Breast Cancer

The present study aimed to develop a multifunctional nanoparticle platform with properties that are beneficial in imaging, targeting, and synergistic cancer phototherapy. To this end, we synthesized novel nanoparticles composed of polydopamine, nano zero-valent iron (nZVI), and reduced graphene oxide (rGO). We immobilized nZVI on the surface of GO (nZVI/GO), then further modified nZVI/GO with dopamine to form polydopamine-conjugated nZVI/rGO (nZVI/rGO@pDA). Because nZVI/rGO@pDA absorbs near infrared radiation (NIR) and binds biomolecules of cancer cells, this platform is highly efficacious in photothermal and photodynamic cancer therapy and enables specific targeting of breast cancer cells. Use of nZVI/rGO@pDA at a low concentration (10 μg/mL) resulted in irreversible damage to MCF-7 cells under NIR irradiation (808 nm) without inducing cytotoxic effects in normal cells. Furthermore, nZVI/rGO@pDA showed high sensitivity in magnetic resonance imaging (MRI), comparable to nZVI@pDA, even at low concentration. Monitoring the treatment response through evaluation of MRI signal intensity of nZVI/rGO@pDA in phototherapeutic therapy revealed that the novel material combines the advantages of nZVI, rGO, and pDA to provide specific targeting capabilities, excellent biocompatibility, and cancer phototherapeutic and tumor imaging abilities. Thus, this platform offers great potential in terms of imaging and therapeutic effects in phototherapy treatment for breast cancer.
A potential role for two brainstem nuclei in craniovascular nociception and the triggering of migraine headache

Aim To use an animal model of migraine to test whether migraine headache might arise from a brainstem-trigeminal nucleus pathway. Methods We measured evoked and spontaneous activity of second-order trigeminovascular neurons in rats to test whether the activity of these neurons increased following the induction of cortical spreading depression or the imposition of light flash – two potential migraine triggers, or headache provokers. We then tested whether drugs that could activate, or inactivate, neurons of the nucleus raphe magnus or the periaqueductal gray matter, would affect any such increases selectively for the dura mater. Results Injection of sodium glutamate (a neuronal excitant) into these two nuclei selectively inhibited the responses of trigeminovascular second-order neurons to dura mater, but not to facial skin, stimulation. Injection of lignocaine (a local anaesthetic) into these nuclei selectively potentiated the responses of these neurons to dura, but not to facial skin, stimulation. Furthermore, injections into either nucleus of glutamate inhibited the increase in the ongoing discharge rate of these neurons produced by cortical spreading depression and light flash. Conclusions These results provide indirect evidence that trigeminovascular nociception may be tightly controlled by these two nuclei, whereas cutaneous trigeminal sensation may be less so. These nuclei may be relays of one possible brainstem-trigeminal pathway that could mediate migraine headache. Modification of neuronal activity in these two nuclei produced by migraine (headache) triggers may lie behind the pain of a migraine attack, at least in some cases.
Dual Circularly Polarized Planar Four-Port MIMO Antenna with Wide Axial-Ratio Bandwidth

A broadband compact-sized planar four-port multiple-input–multiple-output (MIMO) antenna with polarization diversity is presented. The proposed dual circularly polarized (CP) MIMO antenna consists of four G-shaped monopole elements, two of which are left-hand CP and the other two are right-hand CP. A vertical line strip in the G-shaped radiating element acts in balancing the vertical and horizontal electric field components to obtain 90° phase difference between them for circular polarization. Also, an I-shaped strip is incorporated between the ground planes of the G-shaped antenna elements to obtain equal voltage level in the proposed MIMO configuration. The dual circular polarization mechanism of the proposed MIMO/diversity antenna is analysed from the vector current distributions. The impedance bandwidth (S11 ≤ –10 dB) of the MIMO antenna is 105.9% (4–13 GHz) and the 3 dB axial ratio bandwidth (ARBW) is 67.7% (4.2–8.5 GHz), which is suitable for C-band applications. The overall size of the MIMO antenna is 70 × 68 × 1.6 mm3, and the minimum isolation between the resonating elements is 18 dB. The envelope correlation coefficient is less than 0.25, and the peak gain within the resonating band is 6.4 dBi.
Overexpression of OsC3H10, a CCCH-Zinc Finger, Improves Drought Tolerance in Rice by Regulating Stress-Related Genes

CCCH zinc finger proteins are members of the zinc finger protein family, and are known to participate in the regulation of development and stress responses via the posttranscriptional regulation of messenger RNA in animals and yeast. However, the molecular mechanism of CCCHZF-mediated drought tolerance is not well understood. We analyzed the functions of OsC3H10, a member of the rice CCCHZF family. OsC3H10 is predominantly expressed in seeds, and its expression levels rapidly declined during seed imbibition. The expression of OsC3H10 was induced by drought, high salinity and abscisic acid (ABA). Subcellular localization analysis revealed that OsC3H10 localized not only in the nucleus but also to the processing bodies and stress granules upon stress treatment. Root-specific overexpression of OsC3H10 was insufficient to induce drought tolerance, while the overexpression of OsC3H10 throughout the entire plant enhanced the drought tolerance of rice plants. Transcriptome analysis revealed that OsC3H10 overexpression elevated the expression levels of genes involved in stress responses, including LATE EMBRYOGENESIS ABUNDANT PROTEINs (LEAs), PATHOGENESIS RELATED GENEs (PRs) and GERMIN-LIKE PROTEINs (GLPs). Our results demonstrated that OsC3H10 is involved in the regulation of the drought tolerance pathway by modulating the expression of stress-related genes.
Distribution of Nominal Word-Patterns and Roots in Palestinian Arabic: A Developmental Perspective in Early Childhood

Abstract This study investigated the acquisition of word-patterns and roots in the nominal system of the spoken language of Palestinian Arabic (PA) and its distance from Standard Arabic (StA). It described, analyzed, and quantified the nominal system (roots and word-patterns) as reflected in the language corpus of Palestinian-Arab kindergarteners 3 to 6 years old. The results showed that non-linear derived nouns (deverbal nouns) are the most frequently used category (49.5%). Primitive nouns comprise 43.1% of the nouns, whereas linear derived nouns barely exist before children start school (0.3%). Additionally, the results showed that half of the nouns were built from common word-patterns and roots between PA and StA, whereas 30% of the nouns were constructed from different word-patterns with common roots. Although PA and StA have much in common morphologically, there exists a significant degree of divergence.
Comparative diversity analysis of halophiles at two polar saltern systems in Indramayu, West Java, Indonesia

Successive microbes in solar salt ponds are essential since it is well correlated with the quality of salt produced. This research aimed to analyse the microbial diversity of the solar salt ponds in Indonesia, which use high‐density polyethylene in the ponds. There are two systems, that is, an integrated open system (In‐system) and a closed system (Tt‐system). The In‐system uses seawater while the Tt‐system uses seawater from the saline artesian well. Results showed that the In‐system had richer microbes than the Tt‐system. Both systems shared similar halophilic microbes profile. Ponds with low salinity (3–4 Be) had very low archaea, that is, 0·2 and 0·7% for the In‐system and Tt‐system respectively and were dominantly inhabited by phylum Proteobacteria. In the pond with high salinity, that is, 25 Be, both systems were dominated by the phylum Euryarchaeota, family Halobacteriaceae, and genera Halorubrum was dominantly found in In25 ponds and Tt25 ponds. Even though the two systems use the same parent seawater, that is, the Java Sea and share similar microbial composition at the phylum level, we found the dominance identified microbes in both systems were different.
A General Framework for Adaptation of Neural Machine Translation to Simultaneous Translation

Despite the success of neural machine translation (NMT), simultaneous neural machine translation (SNMT), the task of translating in real time before a full sentence has been observed, remains challenging due to the syntactic structure difference and simultaneity requirements. In this paper, we propose a general framework for adapting neural machine translation to translate simultaneously. Our framework contains two parts: prefix translation that utilizes a consecutive NMT model to translate source prefixes and a stopping criterion that determines when to stop the prefix translation. Experiments on three translation corpora and two language pairs show the efficacy of the proposed framework on balancing the quality and latency in adapting NMT to perform simultaneous translation.
Natural selection in the wild

Natural selection is an immense and important subject, yet there have been few attempts to summarize its effects on natural populations, and fewer still which discuss the problems of working with natural selection in the wild. These are the purposes of John Endler's book. In it, he discusses the methods and problems involved in the demonstration and measurement of natural selection, presents the critical evidence for its existence, and places it in an evolutionary perspective. Professor Endler finds that there are a remarkable number of direct demonstrations of selection in a wide variety of animals and plants. The distribution of observed magnitudes of selection in natural populations is surprisingly broad, and it overlaps extensively the range of values found in artificial selection. He argues that the common assumption that selection is usually weak in natural populations is no longer tenable, but that natural selection is only one component of the process of evolution; natural selection can explain the change of frequencies of variants, but not their origins.
Real-Time Fruit Recognition and Grasping Estimation for Robotic Apple Harvesting

Robotic harvesting shows a promising aspect in future development of agricultural industry. However, there are many challenges which are still presented in the development of a fully functional robotic harvesting system. Vision is one of the most important keys among these challenges. Traditional vision methods always suffer from defects in accuracy, robustness, and efficiency in real implementation environments. In this work, a fully deep learning-based vision method for autonomous apple harvesting is developed and evaluated. The developed method includes a light-weight one-stage detection and segmentation network for fruit recognition and a PointNet to process the point clouds and estimate a proper approach pose for each fruit before grasping. Fruit recognition network takes raw inputs from RGB-D camera and performs fruit detection and instance segmentation on RGB images. The PointNet grasping network combines depth information and results from the fruit recognition as input and outputs the approach pose of each fruit for robotic arm execution. The developed vision method is evaluated on RGB-D image data which are collected from both laboratory and orchard environments. Robotic harvesting experiments in both indoor and outdoor conditions are also included to validate the performance of the developed harvesting system. Experimental results show that the developed vision method can perform highly efficient and accurate to guide robotic harvesting. Overall, the developed robotic harvesting system achieves 0.8 on harvesting success rate and cycle time is 6.5 s.
Lost in reviews: Looking for the involvement of stakeholders, patients, public and other non‐researcher contributors in realist reviews

The involvement of non‐researcher contributors (eg, stakeholders, patients and the public, decision and policy makers, experts, lay contributors) has taken a variety of forms within evidence syntheses. Realist reviews are a form of evidence synthesis that involves non‐researcher contributors yet this practice has received little attention. In particular, the role of patient and public involvement (PPI) has not been clearly documented. This review of reviews describes the ways in which contributor involvement, including PPI, is documented within healthcare realist reviews published over the last five years. A total of 448 papers published between 2014 and 2019 were screened, yielding 71 full‐text papers included in this review. Statements about contributor involvement were synthesized across each review using framework analysis. Three themes are described in this article including nomenclature, nature of involvement, and reporting impact.
Effect of lesion diameter and prostate volume on prostate cancer detection rate of magnetic resonance imaging: Transrectal-ultrasonography-guided fusion biopsies using cognitive targeting.

OBJECTIVE This study aimed to evaluate the effect of prostate volume and lesion size on the clinically significant prostate cancer (csPCa) detection rates of transrectal ultrasonography (TRUS)-guided prostate biopsies, performed by a cognitive targeting method for sampling peripheral zone lesions. MATERIAL AND METHODS We retrospectively enrolled 219 consecutive patients, who underwent multiparametric magnetic resonance imaging with a 3-T scanner and had peripheral zone lesions suspected for prostate cancer. All of these patients underwent combined cognitive targeted biopsy of suspicious lesions and TRUS-guided systematic biopsy. The detection rates of csPCa according to different lesion diameters (<5 mm, 5-9.9 mm, and ≥10 mm) and prostate volumes (<30 mL, 30-49.9 mL, 50-79.9 mL, and ≥80 mL) were calculated per lesion basis. In addition, subgroup analysis of csPCa detection rates was performed according to Prostate Imaging Reporting and Data System scores of lesions. RESULTS The csPCa detection rates according to lesion diameters <5 mm, 5-9.9 mm, and ≥10 mm were 4%, 9.8%, and 33.1%, respectively, and were significantly lower for lesions <10 mm (p<0.001). The csPCa detection rates were 61.5%, 24.1%, 16.2%, and 6.9%, respectively, for prostate volumes <30 mL, 30-49.9 mL, 50-79.9 mL, and ≥80 mL, and were significantly higher for prostate volumes <30 mL (p<0.001). CONCLUSIONS Clinicians should be very careful when they prefer cognitive targeted prostatic biopsy in patients with periferal zone lesions less than 10 mm and with prostate volumes greater than 30 mL, because of significantly low csPCa detection rates.
Drug-related problems in head and neck cancer patients identified by repeated medication reviews on consecutive therapy cycles

Background Head and neck cancer (HNC) patients are particularly vulnerable to drug-related problems (DRPs) given the toxicity of concomitant chemoradiotherapy (CCRT). Objective To investigate the number and type of potential DRPs (pDRPs) in HNC outpatients undergoing five consecutive cycles of CCRT. Methods A single-centre, non-randomized, non-interventional, observational study was conducted at the Oncological Outpatient Clinic of the Center for Integrated Oncology at the University Hospital Bonn, Germany. Clinical pharmacists took a comprehensive medication history, documented laboratory data, assessed patients’ symptom burden, and retrospectively performed medication reviews at study entry and on the first day of each therapy cycle without any clinical intervention. Results In 26 patients, the mean number of pDRPs continuously increased during therapy course, from 4.8 (SD 2.7, range 2–12) at cycle 1 to 6.9 (SD 2.6, range 2–12) at cycle 5, with drug-drug interactions, adverse drug reactions, inappropriate durations of use, and inappropriate dosage intervals being the most common. Considering only new and recurrent pDRPs, the mean number was 4.3 (SD 2.3, range 2–9) at cycle 1 and lower in the further therapy course with an average of 1.3 (SD 1.7, range 0–7) at cycle 2 and 1.9 (SD 1.5, range 0–5) at cycle 5. The number of pDRPs was found to be associated with medication regimen complexity and health-related quality of life assessed in the first therapy cycle. Conclusion pDRPs frequently occurred in HNC outpatients demonstrating the need for pharmaceutical care. A methodological framework for repeated medication reviews was established, facilitating implementation into routine healthcare practice.
PartnerCARE—a psycho-oncological online intervention for partners of patients with cancer: study protocol for a randomised controlled feasibility trial

Introduction Cancer burdens not only the patient but also the partner to a comparable extent. Partners of patients with cancer are highly involved in the caring process and therefore often experience distress and report a low quality of life. Interventions for supporting partners are scarce. Existing ones are rarely used by partners because they are often time-consuming per se and offer only limited flexibility with regard to schedule and location. The online intervention PartnerCARE has been developed on the basis of caregiver needs and consists of six consecutive sessions and four optional sessions, which are all guided by an e-coach. The study aims to evaluate feasibility and acceptance of the online intervention PartnerCARE and the related trial process. In addition, first insights of the putative efficacy of PartnerCARE should be gained. Methods and analysis A two-arm parallel-group randomised controlled trial will be conducted to compare the PartnerCARE online intervention with a waitlist control group. The study aims to recruit in total n=60 partners of patients with any type of cancer across different access paths (eg, university medical centres, support groups, social media). Congruent with feasibility study objectives, the primary outcome comprises recruitment process, study procedure, acceptance and satisfaction with the intervention (Client Satisfaction Questionnaire adapted to Internet-based interventions), possible negative effects (Inventory of Negative Effects in Psychotherapy) and dropout rates. Secondary outcomes include quality of life, distress, depression, anxiety, caregiver burden, fear of progression, social support, self-efficacy, coping and loneliness. Online measurements will be performed by self-assessment at three time points (baseline/pre-randomisation, 2 months and 4 months after randomisation). Data analyses will be based on intention-to-treat principle. Ethics and dissemination Ethics approval has been granted by the Ethics Committee of the University of Ulm (No 390/18). Results from this study will be disseminated to relevant healthcare communities, in peer-reviewed journals and at scientific and clinical conferences. Trial registration number DRKS00017019.