Miracle-dz/UniFAR-FTUs huggingface dataset:
Ophthalmological Findings in Youths With a Newly Diagnosed Brain Tumor.

Importance Visual impairment is an irreversible adverse effect in individuals who experienced a childhood brain tumor. Ophthalmological evaluation at diagnosis enables early detection of vision loss, decision-making about treatment, and when applicable, the timely use of visual interventions. However, awareness of visual impairment in clinical practice is suboptimal, and adherence to ophthalmological evaluation needs to be improved. Objective To assess the prevalence and types of abnormal ophthalmological findings in youths with a newly diagnosed brain tumor. Design, Setting, and Participants In this nationwide, prospective cohort study, youths aged 0 to 18 years with a newly diagnosed brain tumor between May 15, 2019, and August 11, 2021, were consecutively enrolled in 4 hospitals in the Netherlands, including the dedicated tertiary referral center for pediatric oncology care. Exposures A standardized and comprehensive ophthalmological examination, including orthoptic evaluation, visual acuity testing, visual field examination, and ophthalmoscopy, was performed within 4 weeks from brain tumor diagnosis. Main Outcomes and Measures The main outcomes were prevalence and types of visual symptoms and abnormal ophthalmological findings at brain tumor diagnosis. Results Of 170 youths included in the study (96 [56.5%] male; median age, 8.3 years [range, 0.2-17.8 years]), 82 (48.2%) had infratentorial tumors; 53 (31.2%), supratentorial midline tumors; and 35 (20.6%), cerebral hemisphere tumors. A total of 161 patients (94.7%) underwent orthoptic evaluation (67 [41.6%] preoperatively; 94 [58.4%] postoperatively); 152 (89.4%), visual acuity testing (63 [41.4%] preoperatively; 89 [58.6%] postoperatively); 121 (71.2%), visual field examination (49 [40.4%] preoperatively; 72 [59.6%] postoperatively); and 164 (96.5%), ophthalmoscopy (82 [50.0%] preoperatively; 82 [50.0%] postoperatively). Overall, 101 youths (59.4%) presented with visual symptoms at diagnosis. Abnormal findings were found in 134 patients (78.8%) during ophthalmological examination. The most common abnormal findings were papilledema in 86 of 164 patients (52.4%) who underwent ophthalmoscopy, gaze deficits in 54 of 161 (33.5%) who underwent orthoptic evaluation, visual field defects in 32 of 114 (28.1%) with reliable visual field examination, nystagmus in 40 (24.8%) and strabismus in 32 (19.9%) of 161 who underwent orthoptic evaluation, and decreased visual acuity in 13 of 152 (8.6%) with reliable visual acuity testing. Forty-five of 69 youths (65.2%) without visual symptoms at diagnosis had ophthalmological abnormalities on examination. Conclusions and Relevance The results of this study suggest that there is a high prevalence of abnormal ophthalmological findings in youths at brain tumor diagnosis regardless of the presence of visual symptoms. These findings support the need of standardized ophthalmological examination and the awareness of ophthalmologists and referring oncologists, neurologists, and neurosurgeons for ophthalmological abnormalities in this patient group.
Factors contributing to tourism demand at major Japanese hot springs

Hot springs are a major tourism resource in nature-based tourism, and the hot springs market is one of the biggest sectors in wellness tourism markets. In the present study, we examine factors contributing to tourism demand for major hot spring resorts in Japan using ordinary least squares regression models and generalized linear mixed models, and compare the estimation results. The results show that significant factors in most of our models are quality of accommodations and the degree of dependence on inbound demand. Furthermore, the number of non-Japanese languages supported on websites of hot spring resorts has a significant impact on inbound demand. Since the results of the present study cover more than 80 hot spring sites, the results highlight common important factors for hot spring resorts. Such widely applicable factors have been missing in previous studies, and the present study fills this research gap.
The effects of B‐cell–activating factor on the population size, maturation and function of murine natural killer cells

The role of B‐cell–activating factor (BAFF) in B‐lymphocyte biology has been comprehensively studied, but its contributions to innate immunity remain unclear. Natural killer (NK) cells form the first line of defense against viruses and tumors, and have been shown to be defective in patients with systemic lupus erythematosus (SLE). The link between BAFF and NK cells in the development and progression of SLE remains unstudied. By assessing NK cell numbers in wild‐type (WT), BAFF−/− (BAFF deficient), BAFF‐R−/− (BAFF receptor deficient), TACI−/− (transmembrane activator and calcium modulator and cyclophilin ligand interactor deficient), BCMA−/− (B‐cell maturation antigen deficient) and BAFF transgenic (Tg) mice, we observed that BAFF signaling through BAFF‐R was essential for sustaining NK cell numbers in the spleen. However, according to the cell surface expression of CD27 and CD11b on NK cells, we found that BAFF was dispensable for NK cell maturation. Ex vivo and in vivo models showed that NK cells from BAFF−/− and BAFF Tg mice produced interferon‐γ and killed tumor cells at a level similar to that in WT mice. Finally, we established that NK cells do not express receptors that interact with BAFF in the steady state or in the BAFF Tg mouse model of SLE. Our findings demonstrate that BAFF has an indirect effect on NK cell homeostasis and no effect on NK cell function.
Double-strand break toxicity is chromatin context independent

Abstract Cells respond to double-strand breaks (DSBs) by activating DNA damage response pathways, including cell cycle arrest. We have previously shown that a single double-strand break generated via CRISPR/Cas9 is sufficient to delay cell cycle progression and compromise cell viability. However, we also found that the cellular response to DSBs can vary, independent of the number of lesions. This implies that not all DSBs are equally toxic, and raises the question if the location of a single double-strand break could influence its toxicity. To systematically investigate if DSB-location is a determinant of toxicity we performed a CRISPR/Cas9 screen targeting 6237 single sites in the human genome. Next, we developed a data-driven framework to design CRISPR/Cas9 sgRNA (crRNA) pools targeting specific chromatin features. The chromatin context was defined using ChromHMM states, Lamin-B1 DAM-iD, DNAseI hypersensitivity, and RNA-sequencing data. We computationally designed 6 distinct crRNA pools, each containing 10 crRNAs targeting the same chromatin state. We show that the toxicity of a DSB is highly similar across the different ChromHMM states. Rather, we find that the major determinants of toxicity of a sgRNA are cutting efficiency and off-target effects. Thus, chromatin features have little to no effect on the toxicity of a single CRISPR/Cas9-induced DSB.
Wearable sensing, big data technology for cardiovascular healthcare: current status and future prospective

Abstract Wearable technology, which can continuously and remotely monitor physiological and behavioral parameters by incorporated into clothing or worn as an accessory, introduces a new era for ubiquitous health care. With big data technology, wearable data can be analyzed to help long-term cardiovascular care. This review summarizes the recent developments of wearable technology related to cardiovascular care, highlighting the most common wearable devices and their accuracy. We also examined the application of these devices in cardiovascular healthcare, such as the early detection of arrhythmias, measuring blood pressure, and detecting prevalent diabetes. We provide an overview of the challenges that hinder the widespread application of wearable devices, such as inadequate device accuracy, data redundancy, concerns associated with data security, and lack of meaningful criteria, and offer potential solutions. Finally, the future research direction for cardiovascular care using wearable devices is discussed.
INTERNAL LIMITING MEMBRANE PEELING DISTORTS THE RETINAL LAYERS AND INDUCES SCOTOMA FORMATION IN THE PERIFOVEAL TEMPORAL MACULA

Supplemental Digital Content is Available in the Text. This retrospective case series study includes 45 patients with an idiopathic macular hole who underwent internal limiting membrane peeling. Their retinal sensitivity in the perifoveal temporal macula decreased significantly 6 months after the surgery. Six patients (13%) developed scotomas with distorted retinal layers specifically in the perifoveal temporal macula. Purpose: To determine whether internal limiting membrane peeling damages retinal function in patients with an idiopathic macular hole. Methods: Retrospective case series. Forty-five eyes of 45 idiopathic macular hole patients who underwent vitrectomy with internal limiting membrane peeling with a minimum follow-up of 6 months. Each patient received a complete ophthalmological examination. The eyes were examined by microperimetry MP-3 in the central 20° visual field and optical coherence tomography angiography in the central 6 × 6 mm area. Results: Six months after the surgery, macular hole closed in each patient. Retinal sensitivity decreased significantly in the perifoveal temporal ETDRS sector (from 24.97 ± 2.67–19.98 ± 5.68 dB, P = 0.001) but not in the other sectors. Six patients (13%) developed 24 scotomas, 62.5% presented in the perifoveal temporal sector. Anatomically, bumps in the outer nuclear layer were discovered concurrent with inner retinal dimples on B-scan images, predominantly (76.8%) in the perifoveal temporal sector, which have not been previously reported. The incidence of outer nuclear layer bumps was significantly higher in patients with scotomas than in those without (83% vs. 18%, P = 0.014). Conclusion: Internal limiting membrane peeling induced functional changes specifically in the perifoveal temporal macula. Distortion in the retinal layers is proposed to underly scotomas pathogenesis.
Differences in prophylactic performance across wound dressing types used to protect from device‐related pressure ulcers caused by a continuous positive airway pressure mask

Prolonged use of continuous positive airway pressure masks, as often required for non‐invasive ventilation, involves a risk for facial tissue breakdown due to the sustained deformations caused by tightening of the stiff mask surfaces to the head and the moist environment. The risk of developing mask‐related facial injuries can be reduced through suitable cushioning materials placed at the skin‐mask interfaces to spread the localised contact forces and disperse the surface and internal tissue stresses. Using an integrated experimental‐computational approach, we compared the biomechanical protective performance of three popular foam‐based wound dressings to that of a market‐lead hydrocolloid dressing when applied to protect the facial skin under a mask. We measured the compressive stiffness properties of the four commercial dressing types in dry and moist conditions, and then fed those to an anatomically realistic finite element model of an adult male head, with an applied simulated mask. Through this process, we calculated the protective efficacy index of each dressing type, indicating the relative contribution of the specified dressing to alleviating facial soft tissue loads with respect to the no‐dressing case. The foam‐based dressings generally performed substantially better than the hydrocolloid, but foam dressings were also demonstrated to vary by their protective performance.
In Vitro Effect of 445 nm Blue Laser and 660 nm Low‐Level Laser on the Quantity and Quality of Human Gingival Fibroblasts

Low‐level laser therapy (LLLT) has several benefits in dentistry, including anti‐inflammatory effects and increased proliferation. This study aimed to investigate the effect of 445 nm blue laser and 660 nm low‐power laser on the quantity and quality of human gingival fibroblasts in vitro. In this in vitro experimental study, 445 nm and 660 nm lasers were irradiated on the samples six times. After examining the cells on the 7th and 14th days, the data were analyzed using ANOVA PASS11 and the post hoc Tukey test. The results showed the positive effect of the 660 nm laser on fibroblast proliferation. The viability on the 7th day was the highest in the control group, lowest in the 445 nm laser group and highest in the 660 nm laser group on the 14th day. In the morphological examination, the cells were spherical with narrow appendages in the control group, spindle‐shaped with lamellipodia appendages in the 660 nm laser group and spherical with no cytoplasmic appendages in the 445 nm laser group. Evidence of necrosis and granulation phenomenon was observed in the 445 nm laser group. The use of the 660 nm low‐power laser, compared with the 445 nm laser, has a positive effect on the quantity and quality of gingival fibroblasts.
Lethal and sublethal effects of thermal stress on octocorals early life‐history stages

The frequency and severity of marine heatwaves causing mass mortality events in tropical and temperate coral species increases every year, with serious consequences on the stability and resilience of coral populations. Although recovery and persistence of coral populations after stress events is closely related to adult fitness, as well as larval survival and settlement, much remains unknown about the effects of thermal stress on early life‐history stages of temperate coral species. In the present study, the reproductive phenology and the effect of increased water temperature (+4°C and +6°C above ambient, 20°C) on larval survival and settlement was evaluated for two of the most representative Mediterranean octocoral species (Eunicella singularis and Corallium rubrum). Our study shows that reproductive behavior is more variable than previously reported and breeding period occurs over a longer period in both species. Thermal stress did not affect the survival of symbiotic E. singularis larvae but drastically reduced the survival of the non‐symbiotic C. rubrum larvae. Results on larval biomass and caloric consumption suggest that higher mortality rates of C. rubrum exposed to increased temperature were not related to depletion of endogenous energy in larvae. The results also show that settlement rates of E. singularis did not change in response to elevated temperature after 20 days of exposure, but larvae may settle fast and close to their native population at 26°C (+6°C). Although previous experimental studies found that adult colonies of both octocoral species are mostly resistant to thermal stress, our results on early life‐history stages suggest that the persistence and inter‐connectivity of local populations may be severely compromised under continued trends in ocean warming.
Predictors of 30‐day and 12‐month mortality in left main stem percutaneous coronary intervention 2016−2020: A study from two UK centers

Left main stem percutaneous coronary intervention (LMS‐PCI) is a complex high‐risk procedure which can be performed as an alternative to coronary artery bypass graft (CABG) procedure in surgical turn‐down patients or where there is equipoise in percutaneous versus surgical strategies. Current guidelines suggest that PCI is an appropriate alternative to CABG in patients with unprotected LMS disease and low SYNTAX score. However, “real world” data on outcomes of LMS‐PCI remain limited. This study aims to quantify and determine predictors of mortality following LMS‐PCI.
Von Hippel–Lindau disease: insights into oxygen sensing, protein degradation, and cancer

Germline loss-of-function mutations of the VHL tumor suppressor gene cause von Hippel–Lindau disease, which is associated with an increased risk of hemangioblastomas, clear cell renal cell carcinomas (ccRCCs), and paragangliomas. This Review describes mechanisms involving the VHL gene product in oxygen sensing, protein degradation, and tumor development and current therapeutic strategies targeting these mechanisms. The VHL gene product is the substrate recognition subunit of a ubiquitin ligase that targets the α subunit of the heterodimeric hypoxia-inducible factor (HIF) transcription factor for proteasomal degradation when oxygen is present. This oxygen dependence stems from the requirement that HIFα be prolyl-hydroxylated on one (or both) of two conserved prolyl residues by members of the EglN (also called PHD) prolyl hydroxylase family. Deregulation of HIF, and particularly HIF2, drives the growth of VHL-defective ccRCCs. Drugs that inhibit the HIF-responsive gene product VEGF are now mainstays of ccRCC treatment. An allosteric HIF2 inhibitor was recently approved for the treatment of ccRCCs arising in the setting of VHL disease and has advanced to phase III testing for sporadic ccRCCs based on promising phase I/II data. Orally available EglN inhibitors are being tested for the treatment of anemia and ischemia. Five of these agents have been approved for the treatment of anemia in the setting of chronic kidney disease in various countries around the world.
The intestine is a major contributor to circulating succinate in mice

The tricarboxylic acid (TCA) cycle is the epicenter of cellular aerobic metabolism. TCA cycle intermediates facilitate energy production and provide anabolic precursors, but also function as intra‐ and extracellular metabolic signals regulating pleiotropic biological processes. Despite the importance of circulating TCA cycle metabolites as signaling molecules, the source of circulating TCA cycle intermediates remains uncertain. We observe that in mice, the concentration of TCA cycle intermediates in the portal blood exceeds that in tail blood indicating that the gut is a major contributor to circulating TCA cycle metabolites. With a focus on succinate as a representative of a TCA cycle intermediate with signaling activities and using a combination of gut microbiota depletion mouse models and isotopomer tracing, we demonstrate that intestinal microbiota is not a major contributor to circulating succinate. Moreover, we demonstrate that endogenous succinate production is markedly higher than intestinal succinate absorption in normal physiological conditions. Altogether, these results indicate that endogenous succinate production within the intestinal tissue is a major physiological source of circulating succinate. These results provide a foundation for an investigation into the role of the intestine in regulating circulating TCA cycle metabolites and their potential signaling effects on health and disease.
A Noniterative Supervised On-Chip Training Circuitry for Reservoir Computing Systems

Artificial neural networks (ANNs) is an exponentially growing field, mainly because of its wide range of applications to everyday life such as pattern recognition or time series forecasting. In particular, reservoir computing (RC) arises as an optimal computational framework suited for temporal/sequential data analysis. The direct on-silicon implementation of RCs may help to minimize power and maximize processing speed, that is especially relevant in edge intelligence applications where energy storage is considerably restricted. Nevertheless, most of the RC hardware solutions present in the literature perform the training process off-chip at the server level, thus increasing processing time and overall power dissipation. Some studies integrate both learning and inference on the same chip, although these works are normally oriented to implement unsupervised learning (UL) [with a lower expected accuracy than supervised learning (SL)], or propose iterative solutions (with a subsequent higher power consumption). Therefore, the integration of RC systems including both inference and a fast noniterative SL method is still an incipient field. In this article, we propose a noniterative SL methodology for RC systems that can be implemented on hardware either sequentially or fully parallel. The proposal presents a considerable advantage in terms of energy efficiency (EE) and processing speed if compared to traditional off-chip methods. In order to prove the validity of the model, a cyclic echo state NN with on-chip learning capabilities for time series prediction has been implemented and tested in a field-programmable gate array (FPGA). Also, a low-cost audio processing method is proposed that may be used to optimize the sound preprocessing steps.
MLMG-SGG: Multilabel Scene Graph Generation With Multigrained Features

As an important and challenging problem in computer vision, scene graph generation (SGG) aims to find out the underlying semantic relationships among objects from a given image for scene understanding. Usually, prevalent SGG approaches adopt a learning pipeline with the assumption that there exists only a single relationship for a particular object pair. Considering the common phenomenon that a pair of objects can be attached by multiple relationships, we propose a multi-label scene graph generation pipeline with multi-grained features (MLMG-SGG), which formulates the relationship detection as a multi-label classification problem during training while generating multigraphs at inference time. In order to better model the fine-grained relationships, the proposed pipeline encodes the feature representation of SGG on different spatial scales by a specially designed Multi-Grained Module (MGM), resulting in the multi-grained (i.e., object-level and region-level) features of objects. Experimental results over the benchmark dataset demonstrate the significant performance gain of the proposed pipeline used as a plug-in for the state-of-the-art methods.
Identification of thioredoxin domain containing family members' expression pattern and prognostic value in diffuse gliomas via in silico analysis

Gliomas are the most prevalent primary tumors of the central nervous system. Their aggressive nature and the obstacles arising during therapy highlights the importance of finding new prognostic markers and therapy targets for gliomas. TXNDC genes are members of the thioredoxin superfamily and were shown to play a role in redox homeostasis, protein folding, electron transfer and also acting as cellular adapters. The well known contribution of these processes in cancer progression prompted us to investigate if TXNDC family members may also play a role in carcinogenesis, in particular diffuse gliomas.
Saving zone of stasis in burn wounds by nanoliposomal Mg‐ATP

ATP is a crucial molecule for every energy‐dependent process in cells. In ischemic tissues, ATP production declines, and it finally results in cell death. One of the most common strategies in burn wound management is saving the zone of ischemia. In the current study, Mg‐ATP‐containing nanoliposomes were formulated and studied in vitro and in vivo. The particle size of the vesicles was between 50 and 100 nm and the mean zeta potential was −4.05 ± 0.52 mV as evaluated by dynamic light scattering and Zeta sizer instrument, respectively. The encapsulation efficiency of ATP in the nanoliposomes was found to be 9.3%. The morphology and size of nanoliposomes were further studied by transmission electron microscopy. The standard MTT assay revealed no cytotoxicity of the nanoliposomes when tested on the rat fibroblast cells. Forty rats were randomly divided into four groups (N = 10 each). Burn wounds were created by burn comb model on the back of the rats and the zone of stasis in each group was treated every 12 h for 3 days by injecting them with the Mg‐ATP‐nanoliposomes. Control samples included empty nanoliposomes, unencapsulated Mg‐ATP and the Krebs–Henseleit buffer. Laser Doppler flowmetry results revealed that blood perfusion in the zone of ischemia in rats treated with Mg‐ATP‐nanoliposomes was more than in the other groups (p < 0.05). Histopathology revealed saving zone of stasis by Mg‐ATP‐nanoliposomes. Findings obtained in this study demonstrated that the formulated Mg‐ATP‐nanoliposome has the potential to save the stasis zone in burn wounds.