Miracle-dz/UniFAR-FTUs huggingface dataset:
MGRNN: Structure Generation of Molecules Based on Graph Recurrent Neural Networks

Molecular structure generation is a critical problem for materials science and has attracted growing attention. The problem is challenging since it requires to generate chemically valid molecular structures. Inspired by the recent work in deep generative models, we propose a graph recurrent neural network model for drug molecular structure generation, briefly called MGRNN (Molecular Graph Recurrent Neural Networks). MGRNN combines the advantages of both iterative molecular generation algorithm and the efficiency of the training strategies. Moreover, MGRNN shows: (i) efficient computation for training; (ii) high model robustness for data; and (iii) an iterative sampling process, which allows to use chemical domain expertise for valency checking. Experimental results show that MGRNN is able to generate 69 % chemically valid molecules even without chemical knowledge and 100 % valid molecules with chemical rules.
Understanding neural signals of post-decisional performance monitoring: An integrative review

Performance monitoring is a key cognitive function, allowing to detect mistakes and adapt future behavior. Post-decisional neural signals have been identified that are sensitive to decision accuracy, decision confidence and subsequent adaptation. Here, we review recent work that supports an understanding of late error/confidence signals in terms of the computational process of post-decisional evidence accumulation. We argue that the error positivity, a positive-going centro-parietal potential measured through scalp electrophysiology, reflects the post-decisional evidence accumulation process itself, which follows a boundary crossing event corresponding to initial decision commitment. This proposal provides a powerful explanation for both the morphological characteristics of the signal and its relation to various expressions of performance monitoring. Moreover, it suggests that the error positivity –a signal with thus far unique properties in cognitive neuroscience – can be leveraged to furnish key new insights into the inputs to, adaptation, and consequences of the post-decisional accumulation process.
Economic burden in treated Japanese patients with relapsed/refractory large B-cell lymphoma

Aim: To understand the economic burden of relapsed and refractory large B-cell lymphoma patients in Japan treated with salvage chemotherapy. Patients & methods: Patients who received systemic therapy after first-line treatment were analyzed to assess its associated cost and resource use using a retrospective claims database. The impact of COVID-19 was assessed separately. Results & conclusion: This study identified 2927 and 1085 patients in the second- (2L) and third-line (3L) cohorts. The median ages for the 2L and 3L cohorts were 71 and 70 years, respectively, with Charlson Comorbidity Score of 3. A majority of the patients had limited stem cell transplant due to advanced age. Median lengths of inpatient stay for the 2L and 3L cohorts were 118 and 116 days, respectively. The majority of costs were attributed to inpatient costs, and limited COVID-19 impact was observed in this study.
Getting Insights From Twitter: What People Want to Touch in Daily Life

Understanding what people want to touch in daily life has been one of the central topics in the fields of haptic science, engineering, and marketing. Several studies have addressed the topic, however, their findings were highly dependent on the experimental stimuli in the laboratory environment. In this study, we tried to gain insights into targets that people want to touch in daily life by conducting a Twitter survey. We collected a considerable amount of Japanese Twitter posts containing references to the desire for touch. To capture the motivation underlying these desires in relation to haptic properties, we used several queries that comprehensively covered exploratory procedures. The results showed that targets that people wanted to touch depended on the exploratory procedures in the queries used (e.g., “want to stroke” tended to target people and animals). We also found that these targets were desirable to touch not only for their haptic properties but also as a means of communicating with other people or living animals. Our findings would be important for understanding human haptic function in the real world and for developing consumer haptic displays and applications.
The FDA-Approved Anthelmintic Pyrvinium Pamoate Inhibits Pancreatic Cancer Cells in Nutrient-Depleted Conditions by Targeting the Mitochondria

Pancreatic ductal adenocarcinoma (PDAC) is a lethal aggressive cancer, in part due to elements of the microenvironment (hypoxia, hypoglycemia) that cause metabolic network alterations. The FDA-approved antihelminthic pyrvinium pamoate (PP) has previously been shown to cause PDAC cell death, although the mechanism has not been fully determined. We demonstrated that PP effectively inhibited PDAC cell viability with nanomolar IC50 values (9–93 nmol/L) against a panel of PDAC, patient-derived, and murine organoid cell lines. In vivo, we demonstrated that PP inhibited PDAC xenograft tumor growth with both intraperitoneal (IP; P < 0.0001) and oral administration (PO; P = 0.0023) of human-grade drug. Metabolomic and phosphoproteomic data identified that PP potently inhibited PDAC mitochondrial pathways including oxidative phosphorylation and fatty acid metabolism. As PP treatment reduced oxidative phosphorylation (P < 0.001), leading to an increase in glycolysis (P < 0.001), PP was 16.2-fold more effective in hypoglycemic conditions similar to those seen in PDAC tumors. RNA sequencing demonstrated that PP caused a decrease in mitochondrial RNA expression, an effect that was not observed with established mitochondrial inhibitors rotenone and oligomycin. Mechanistically, we determined that PP selectively bound mitochondrial G-quadruplexes and inhibited mitochondrial RNA transcription in a G-quadruplex–dependent manner. This subsequently led to a 90% reduction in mitochondrial encoded gene expression. We are preparing to evaluate the efficacy of PP in PDAC in an IRB-approved window-of-opportunity trial (IND:144822).
Efficacy and safety of rituximab in autoimmune pancreatitis type 1: our experiences and systematic review of the literature

Abstract Introduction Autoimmune pancreatitis (AIP) is a special form of pancreatitis that responds well to glucocorticoid (GC) treatment. Relapses of AIP are common. The anti-CD20 antibody rituximab (RTX) has shown promising results in GC refractory cases, but long-term data are scarce. The study aims to determine the clinical and imaging response to RTX and summarize the existing data on RTX therapy in patients with AIP type 1 in the literature. Patients and methods Retrospective analysis of electronic medical records was conducted. Additionally, we conducted a systematic review of the literature concerning RTX use in AIP type 1. Results Twelve (11.7%) of 103 patients with AIP type 1 were treated with RTX during the study period: eight (66.7%) achieved complete and four (33.3%) partial remission. RTX was discontinued in one patient who developed fever and reactivation of latent tuberculosis. None of the remaining 11 patients relapsed during a median follow-up of 17 months. No significant differences were detected in baseline clinical characteristics or history of relapse between the patients who obtained complete and partial remission. Altogether, eight studies with 110 AIP type-1 patients treated with RTX were analyzed. Adverse effects ranged from 11–43% and the relapse-free period during follow-up (range 2–173 months) ranged from 38–94%. Conclusions Our results confirm that RTX is efficacious in the treatment of AIP type 1 by inducing remission and preventing relapse. In addition, there are few adverse effects of the treatment.
The Influence of Chronic Diseases on Self-Reported Work Disability

Objective: To investigate the relationship between the types of chronic diseases and self-reported work disability. Methods: We used data from the Korean Labor and Income Panel Study from waves 6 to 21 conducted from 2003 to 2018. New cases of work disability were defined as those who reported that they had work limitations due to their health problems. Information on chronic disease was collected using a questionnaire during the sixth wave of the survey. To evaluate the effects of chronic disease on self-reporting work disability, Cox proportional hazard models were used. Results: The three most influential diseases on work disability were ophthalmologic diseases, chronic kidney diseases, and cardiovascular diseases during the 15-year follow-up period. Conclusion: Work disability is strongly and significantly associated with the aforementioned chronic diseases.
In vivo wide‐field voltage imaging in zebrafish with voltage‐sensitive dye and genetically encoded voltage indicator

The brain consists of neural circuits, which are assemblies of various neuron types. For understanding how the brain works, it is essential to identify the functions of each type of neuron and neuronal circuits. Recent advances in our understanding of brain function and its development have been achieved using light to detect neuronal activity. Optical measurement of membrane potentials through voltage imaging is a desirable approach, enabling fast, direct, and simultaneous detection of membrane potentials in a population of neurons. Its high speed and directness can help detect synaptic and action potentials and hyperpolarization, which encode critical information for brain function. Here, we describe in vivo voltage imaging procedures that we have recently established using zebrafish, a powerful animal model in developmental biology and neuroscience. By applying two types of voltage sensors, voltage‐sensitive dyes (VSDs, Di‐4‐ANEPPS) and genetically encoded voltage indicators (GEVIs, ASAP1), spatiotemporal dynamics of voltage signals can be detected in the whole cerebellum and spinal cord in awake fish at single‐cell and neuronal population levels. Combining this method with other approaches, such as optogenetics, behavioral analysis, and electrophysiology would facilitate a deeper understanding of the network dynamics of the brain circuitry and its development.
The sexual spore pigment asperthecin is required for normal ascospore production and protection from UV light in Aspergillus nidulans

Abstract Many fungi develop both asexual and sexual spores that serve as propagules for dissemination and/or recombination of genetic traits. Asexual spores are often heavily pigmented and this pigmentation provides protection from UV light. However, little is known about any purpose pigmentation that may serve for sexual spores. The model Ascomycete Aspergillus nidulans produces both green pigmented asexual spores (conidia) and red pigmented sexual spores (ascospores). Here we find that the previously characterized red pigment, asperthecin, is the A. nidulans ascospore pigment. The asperthecin biosynthetic gene cluster is composed of three genes: aptA, aptB, and aptC, where deletion of either aptA (encoding a polyketide synthase) or aptB (encoding a thioesterase) yields small, mishappen hyaline ascospores; while deletion of aptC (encoding a monooxygenase) yields morphologically normal but purple ascospores. ∆aptA and ∆aptB but not ∆aptC or wild type ascospores are extremely sensitive to UV light. We find that two historical ascospore color mutants, clA6 and clB1, possess mutations in aptA and aptB sequences, respectively.
CX-5461 Sensitizes DNA Damage Repair–proficient Castrate-resistant Prostate Cancer to PARP Inhibition

Monotherapy with PARP inhibitors is effective for the subset of castrate-resistant prostate cancer (CRPC) with defects in homologous recombination (HR) DNA repair. New treatments are required for the remaining tumors, and an emerging strategy is to combine PARP inhibitors with other therapies that induce DNA damage. Here we tested whether PARP inhibitors are effective for HR-proficient CRPC, including androgen receptor (AR)-null tumors, when used in combination with CX-5461, a small molecule that inhibits RNA polymerase I transcription and activates the DNA damage response, and has antitumor activity in early phase I trials. The combination of CX-5461 and talazoparib significantly decreased in vivo growth of patient-derived xenografts of HR-proficient CRPC, including AR-positive, AR-null, and neuroendocrine tumors. CX-5461 and talazoparib synergistically inhibited the growth of organoids and cell lines, and significantly increased the levels of DNA damage. Decreased tumor growth after combination therapy was maintained for 2 weeks without treatment, significantly increasing host survival. Therefore, combination treatment with CX-5461 and talazoparib is effective for HR-proficient tumors that are not suitable for monotherapy with PARP inhibitors, including AR-null CRPC. This expands the spectrum of CRPC that is sensitive to PARP inhibition.
Seasonal variation of inter-limb jumping asymmetries in youth team-sport athletes

ABSTRACT The main objective of the present study was to provide seasonal variation data for inter-limb asymmetry in youth elite team-sport athletes. Fifty-nine players performed the single-leg countermovement jump (SLCMJ) and the one leg hop for distance (OLHT) tests during pre-season, mid-season and end-season. A repeated-measures analysis of variance was conducted to determine magnitude differences in asymmetry scores between time points. Kappa coefficients (κ) were calculated to determine the levels of agreement for the direction of asymmetry. When comparing inter-limb asymmetry magnitudes across the season, the SLCMJ test showed significantly higher asymmetries at mid-season in comparison with pre-season and end-season (p< 0.01, d= −1.03 for pre to mid; p< 0.01, d= 1.12 for pre to end). However, OLHT inter-limb asymmetry magnitude remained consistent throughout the season (ES range = −0.02 to −0.06). For the direction of asymmetry, levels of agreement ranged from poor to slight in the SLCMJ (k= −0.10 to 0.18) and in the OLHT (k= −0.21 to 0.18). No significant differences were found between mean asymmetry values at any time point or for either test when comparing males and females. In conclusion, jump height asymmetry during the SLCMJ was the only metric to show significant magnitude changes across the season.
Anticancer effect of myristicin on hepatic carcinoma and related molecular mechanism

Abstract Context Myristicin is a natural active compound that has inflammatory, antimicrobial and anti-proliferative properties. Yet, its effect on hepatic carcinoma has not been investigated. Objective To explore the role and related molecular mechanism of myristicin in hepatic carcinoma in vitro. Materials and methods Human hepatic carcinoma cell lines (Huh-7 and HCCLM3 cells) were treated with different concentrations of myristicin (0.5, 1 and 5 mM) for 24, 48 and 72 h. Then, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium assay (MTT), flow cytometer (FCM) analysis and transwell assay were performed to determine cell proliferation, apoptosis and migration/invasion, respectively. Protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X (Bax), E-cadherin, N-cadherin and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway-related proteins were detected using Western blot assay. Gene expression was determined using quantitative real time-polymerase chain reaction (qRT-PCR). Results Myristicin inhibited cell proliferation and induced apoptosis in Huh-7 and HCCLM3 cells; suppressed cell migration and invasion ability, and increased E-cadherin expression and decreased N-cadherin expression, thereby inhibiting epithelial–mesenchymal transition (EMT). Finally, the findings indicated that myristicin decreased phosphorylated (p)-mTOR and p-AKT expression at the protein level. Discussion and conclusions Myristicin exerts an efficient therapeutic effect on hepatic carcinoma by suppressing PI3K/Akt/mTOR signalling pathway; thus, it may be used as a new potential drug for hepatic carcinoma treatment.
Contrast Sensitivity in Early to Intermediate Age-Related Macular Degeneration (AMD)

ABSTRACT Purpose Previous studies indicated that advanced age-related macular degeneration (AMD) affects contrast sensitivity (CS) in humans. The CS results for early/intermediate AMD patients are contradictory. The purpose of this study was to determine if CS testing discriminates early/intermediate AMD patients with normal acuity from normal patients. Methods Forty-nine subjects (25 control and 24 early/intermediate AMD patients) were chosen for this project. The age (p = .16) and acuity (p = .34) was not significantly different between the groups. The average simplified AREDS AMD grade for the AMD patients was 2.75 ± 1.03. Three CS functions employing a descending method of limits were measured at the fovea (1. stationary stimulus and, 2. 16 Hz counter-phase stimulus under photopic conditions and 3. the stationary stimulus viewed through a 2 log unit neutral density filter (mesopic condition, background luminance of 1 cd/m2)) and at 4 deg right or left of the fovea with a horizontally oriented sine wave grating (5 deg diameter) viewed on a VPixx monitor (luminance of 100 cd/m2). Results The early AMD patients were no different from the control patients for any test condition. The intermediate AMD patients were significantly different from the control patients for the mesopic CS function (p = .05). Post-hoc 2-sample t-tests for the intermediate AMD patients were significantly different from the control patients under the stationary photopic and mesopic conditions for the 1.5 cycle per degree stimulus. Conclusions Group differences in CS were only found in intermediate AMD patients. The loss in CS increased for the intermediate AMD patients under low light levels. Thus, CS may not be the optimal test to discriminate early AMD from control patients so other tests measured under dark adapted conditions should be investigated.
Emotional regularity: associations with personality, psychological health, and occupational outcomes

ABSTRACT Emotional regularity is the degree to which a person maintains and returns to a set of emotional states over time. The present investigation examined associations between emotional regularity and extant emotion measures as well as psychologically relevant dimensions of personality, health, and real-world occupational outcomes. Participants included 598 U.S. adults who provided daily experience sampling reports on their emotional states for approximately two months. Results suggest that emotional regularity was related to, but distinct from, well-established measures of emotion including emotional intensity, variability, covariation, inertia, granularity, and emodiversity. Furthermore, emotional regularity significantly predicted measures of personality, psychological health, and occupational outcomes even when accounting for extant emotion measures and sociodemographic covariates. Finally, it explained modest (7.5%) improvement (in terms of cross-validated RSq.) over baseline models containing emotional intensity, variability, and sociodemographic covariates. These findings suggest that emotional regularity may provide an important indicator of healthy emotional functioning and may be a promising area for further scientific discovery.
The Lived Experience of a Newly Diagnosed Older Person With HIV in Ukraine

Low- and middle-income countries are home to 80% of older people with HIV (OPWH). Ukrainian OPWH experience higher mortality and decreased antiretroviral therapy (ART) initiation than younger patients, but there is little data examining OPWH’s perspectives around new diagnosis and impact on care. In this study, we examined accounts of 30 newly diagnosed OPWH in Ukraine, exploring challenges faced in the peri-diagnosis period. Themes emerged representing the longitudinal coping process: OPWH (1) viewed themselves as low risk before diagnosis; (2) experienced HIV diagnosis as a traumatic event challenging their self-image; (3) used disclosure to seek support among a small circle of family, friends, or health care providers; (4) avoided disclosure to outsiders including primary care providers for fears of stigma and breaches in confidentiality; (5) viewed age as an asset; and (6) used HIV diagnosis as starting point for growth. These findings highlight the need for age-specific programming to increase HIV knowledge and coping, increase screening, and improve long-term planning.
Dung beetle community assemblages in a southern African landscape: niche overlap between domestic and wild herbivore dung

Abstract Dung beetles provide important ecosystem functions in semiarid environments, improving the physiochemical characteristics of the soil through tunnelling and burying nutrient-rich dung. In sub-Saharan Africa, diverse indigenous mammal communities support highly abundant dung beetle populations in savannah ecosystems. However, the conversion of landscapes to livestock agriculture may result in changes in the abundance and diversity of wild mammal species. This is likely to have significant impacts on dung beetle communities, particularly because domestic livestock dung may be contaminated with toxic residues of veterinary parasiticides. The environmental impact is likely to be affected by the degree of niche overlap between the beetle communities that colonize cattle dung and those that colonize the dung of wild mammals. We compared dung beetle communities between a pristine national park habitat dominated by large wild herbivores, and a pastoral farming community dominated by domestic livestock. Diurnal dung beetles were attracted to cattle dung in greater abundance and diversity compared to elephant, zebra or giraffe dung. Nocturnal/crepuscular dung beetles were attracted to non-ruminant dung (elephant and zebra) in higher abundance compared to ruminant dung (cattle and giraffe). Although there were no clear trophic specializations, three diurnal species showed an association with cattle dung, whereas eight nocturnal/crepuscular species showed an association with non-ruminant (elephant and zebra) dung. Diurnal species may be at greater risk from the toxic effects of residues of veterinary parasiticides in domestic livestock dung. Although many species showed trophic associations with wild herbivore dung, these beetles can utilize a wide range of dung and will readily colonize cattle dung in the absence of other options. As more land is converted to livestock agriculture, the contamination of dung with toxic residues from veterinary parasiticides could therefore negatively impact the majority of dung beetle species.
Jaridon 6, a new diterpene from Rabdosia rubescens (Hemsl.) Hara, can display anti‐gastric cancer resistance by inhibiting SIRT1 and inducing autophagy

Tumor resistance is the main cause of treatment failure and is associated with many tumor factors. Jaridon 6, a new diterpene extracted from Rabdosia rubescens (Hemsl.) Hara, which has been previously extracted by our research team, has been tested having more obvious advantages in resistant tumor cells. However, its mechanism is unclear. In this study, we studied the effect and the specific mechanism of Jaridon 6 in resistant gastric cancer cells. Cytotoxicity test, colony test, western blotting, and nude test verified the anti‐drug resistance ability of Jaridon 6 in the MGC803/PTX and MGC803/5‐Fu cells. Jaridon 6 has shown obvious inhibitory effects in the sirtuin 1 (SIRT1) enzyme test. Transmission electron microscopy and immunofluorescence tests further proved the autophagic action of Jaridon 6. Jaridon 6 could inhibit the proliferation of the resistant gastric cancer cell in vivo and in vitro. Jaridon 6 inhibited SIRT1 enzyme and induced autophagy by inhibiting the phosphoinositide 3‐kinase/protein kinase B (PI3K/AKT) pathway. Thus, it may be considered for treating gastric cancer resistance by individual or combined administration, as an SIRT1 inhibitor and autophagy inducer.