Miracle-dz/UniFAR-FTUs huggingface dataset:
Ultrafast optical clearing method for three-dimensional imaging with cellular resolution

Significance Most biological tissue is opaque, and the inside fine structures are invisible even with a microscope. Optical clearing methods can reduce the scattering and enable us to “look” inside the biological samples. Current optical clearing methods suffer from large time consumption, tissue distortion, and fluorescence quenching, which greatly limit their applications. Here, we describe a nontoxic ultrafast optical clearing method (FOCM), which could clarify 300-µm-thick brain slices within 2 min without morphology distortion. The fluorescence can be preserved up to 86% even after 11 d. Besides, the cheap reagents and easy operation makes our method have great potential to be widely used. Besides the brain slices, our method can also be applied to other biological tissues. Optical clearing is a versatile approach to improve imaging quality and depth of optical microscopy by reducing scattered light. However, conventional optical clearing methods are restricted in the efficiency-first applications due to unsatisfied time consumption, irreversible tissue deformation, and fluorescence quenching. Here, we developed an ultrafast optical clearing method (FOCM) with simple protocols and common reagents to overcome these limitations. The results show that FOCM can rapidly clarify 300-µm-thick brain slices within 2 min. Besides, the tissue linear expansion can be well controlled by only a 2.12% increase, meanwhile the fluorescence signals of GFP can be preserved up to 86% even after 11 d. By using FOCM, we successfully built the detailed 3D nerve cells model and showed the connection between neuron, astrocyte, and blood vessel. When applied to 3D imaging analysis, we found that the foot shock and morphine stimulation induced distinct c-fos pattern in the paraventricular nucleus of the hypothalamus (PVH). Therefore, FOCM has the potential to be a widely used sample mounting media for biological optical imaging.
A Blind Spectrum Sensing Method Based on Deep Learning

Spectrum sensing is one of the technologies that is used to solve the current problem of low utilization of spectrum resources. However, when the signal-to-noise ratio is low, current spectrum sensing methods cannot well-handle a situation in which the prior information of the licensed user signal is lacking. In this paper, a blind spectrum sensing method based on deep learning is proposed that uses three kinds of neural networks together, namely convolutional neural networks, long short-term memory, and fully connected neural networks. Experiments show that the proposed method has better performance than an energy detector, especially when the signal-to-noise ratio is low. At the same time, this paper also analyzes the effect of different long short-term memory layers on detection performance, and explores why the deep-learning-based detector can achieve better performance.
Inhibition of ATM increases interferon signaling and sensitizes pancreatic cancer to immune checkpoint blockade therapy.

Combinatorial strategies are needed to overcome the resistance of pancreatic cancer to immune checkpoint blockade (ICB). DNA damage activates the innate immune response and improves ICB efficacy. Since ATM is an apical kinase in the radiation-induced DNA damage response, we investigated the effects of ATM inhibition and radiation on pancreatic tumor immunogenicity. ATM was inhibited through pharmacologic and genetic strategies in human and murine pancreatic cancer models both in vitro and in vivo. Tumor immunogenicity was evaluated after ATM inhibition alone and in combination with radiation by assessing TBK1 and Type I Interferon (T1IFN) signaling as well as tumor growth following PD-L1/PD-1 checkpoint inhibition. Inhibition of ATM increased tumoral T1IFN expression in a cGAS/STING-independent, but TBK1 and SRC -dependent manner. The combination of ATM inhibition with radiation further enhanced TBK1 activity, T1IFN production, and antigen presentation. Furthermore, ATM silencing increased PD-L1 expression and increased the sensitivity of pancreatic tumors to PD-L1 blocking antibody in association with increased tumoral CD8+ T cells and established immune memory. In patient pancreatic tumors, low ATM expression inversely correlated with PD-L1 expression. Taken together, these results demonstrate that the efficacy of ICB in pancreatic cancer is enhanced by ATM inhibition and further potentiated by radiation as a function of increased tumoral immunogenicity, underscoring the potential of ATM inhibition in combination with ICB and radiation as an efficacious treatment strategy for pancreatic cancer.
T Cell–Dependent Maturation of Pathogen-Specific Igs in the Antrum of Chronically Helicobacter pylori–Infected Patients

Key Points Gastric PC acquire high rates of somatic hypermutations during H. pylori infection. Gastric poly- and H. pylori–specific Ig evolve from Ag-driven and T cell–dependent responses. VH genes of H. pylori–specific Ig resemble MALT B cell lymphoma Ig genes. Mucosal plasma cells (PC) and Ig production are essential to fend pathogens and to maintain mucosal homeostasis. In human Helicobacter pylori infection, mucosal PC express inducible NO synthase (iNOS), which positively correlates with clearance of experimental human infection. To characterize Ig genes and specificities of antral mucosal iNOS+ and iNOS− PC in H. pylori infection, we sequenced rearranged Ig genes from single cell–sorted PC from biopsy specimens of chronically infected patients and analyzed them with respect to their molecular features. The binding specificity of individual PC’s Ig was determined following recombinant expression. We identified high rates of somatic hypermutations, especially targeting RGYW/WRCY hotspot motifs in the individual Ig genes, indicating T cell–dependent maturation. For seven of 14 recombinantly expressed Ig, Ag specificity could be determined. Two clones reacted to H. pylori proteins, and five were found to be polyreactive against LPSs, dsDNA, and ssDNA. All specific Ig originated from iNOS+ PC. H. pylori–specific Ig are encoded by V and J family genes previously shown to be also used in rearranged Ig loci of MALT B cell lymphomas. In summary, mucosal iNOS+ PC producing H. pylori–specific Ig accumulate in infection and appear to be a product of T cell–dependent B cell maturation. Moreover, the Ig’s molecular features partly resembled that of MALT B cell lymphoma Ig genes, suggestive of a mechanism in which a progressive molecular evolution of pathogen-specific B cells to MALT B cell lymphoma occurs.
Rapid Detection of Adulterants in Whey Protein Supplement by Raman Spectroscopy Combined with Multivariate Analysis

The growing demand for whey protein supplements has made them the target of adulteration with cheap substances. Therefore, Raman spectroscopy in tandem with chemometrics was proposed to simultaneously detect and quantify three common adulterants (creatine, l-glutamine and taurine) in whey protein concentrate (WPC) powder. Soft independent modeling class analogy (SIMCA) and partial least squares discriminant analysis (PLS-DA) models were built based on two spectral regions (400–1800 cm−1 and 500–1100 cm−1) to classify different types of adulterated samples. The most effective was the SIMCA model in 500–1100 cm−1 with an accuracy of 96.9% and an error rate of 5%. Partial least squares regression (PLSR) models for each adulterant were developed using two different Raman spectral ranges (400–1800 cm−1 and selected specific region) and data pretreatment methods. The determination coefficients (R2) of all models were higher than 0.96. PLSR models based on typical Raman regions (500–1100 cm−1 for creatine and taurine, the combination of range 800–1000 cm−1 and 1300–1500 cm−1 for glutamine) were superior to models in the full spectrum. The lowest root mean squared error of prediction (RMSEP) was 0.21%, 0.33%, 0.42% for creatine, taurine and glutamine, and the corresponding limit of detection (LOD) values for them were 0.53%, 0.71% and 1.13%, respectively. This proves that Raman spectroscopy with the help of multivariate approaches is a powerful method to detect adulterants in WPC.
The Genetics of Human Skin and Hair Pigmentation.

Human skin and hair color are visible traits that can vary dramatically within and across ethnic populations. The genetic makeup of these traits-including polymorphisms in the enzymes and signaling proteins involved in melanogenesis, and the vital role of ion transport mechanisms operating during the maturation and distribution of the melanosome-has provided new insights into the regulation of pigmentation. A large number of novel loci involved in the process have been recently discovered through four large-scale genome-wide association studies in Europeans, two large genetic studies of skin color in Africans, one study in Latin Americans, and functional testing in animal models. The responsible polymorphisms within these pigmentation genes appear at different population frequencies, can be used as ancestry-informative markers, and provide insight into the evolutionary selective forces that have acted to create this human diversity. Expected final online publication date for the Annual Review of Genomics and Human Genetics Volume 22 is August 30, 2019. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Mapping access to domestic water supplies from incomplete data in developing countries: An illustrative assessment for Kenya

Water point mapping databases, generated through surveys of water sources such as wells and boreholes, are now available in many low and middle income countries, but often suffer from incomplete coverage. To address the partial coverage in such databases and gain insights into spatial patterns of water resource use, this study investigated the use of a maximum entropy (MaxEnt) approach to predict the geospatial distribution of drinking-water sources, using two types of unimproved sources in Kenya as illustration. Geographic locations of unprotected dug wells and surface water sources derived from the Water Point Data Exchange (WPDx) database were used as inputs to the MaxEnt model alongside geological/hydrogeological and socio-economic covariates. Predictive performance of the MaxEnt models was high (all > 0.9) based on Area Under the Receiver Operator Curve (AUC), and the predicted spatial distribution of water point was broadly consistent with household use of these unimproved drinking-water sources reported in household survey and census data. In developing countries where geospatial datasets concerning drinking-water sources often have necessarily limited resolution or incomplete spatial coverage, the modelled surface can provide an initial indication of the geography of unimproved drinking-water sources to target unserved populations and assess water source vulnerability to contamination and hazards.
The First Molecular and Phenotypic Characterization of the Invasive Population of Aedes albopictus (Diptera: Culicidae) from the Central Balkans

Abstract Aedes (Stegomya) albopictus (Skuse 1984), the Asian tiger mosquito, represents the most invasive and one of the medically most important mosquito vectors. Although native to South East Asia, the species has recently spread globally, and was registered in the city of Novi Sad (Serbia, Central Balkans) in August 2018. We characterized the invasive population using phenotypic (wing size and shape) and molecular (nuclear, internal transcribed spacer 2- ITS2, and mitochondrial, cytochrome c oxidase subunit I- COI) markers. The results of phenotypic analyses indicated that the Serbian population could be differentiated from the native (Thailand) and invasive (Hawaii and Florida) populations due to restricted gene flow, founder effect, and supposed different strain origin. The Serbian population showed genetic homogeneity, indicative of a small founder number (bottleneck invasion model). Despite the incorporation of ITS2 GenBank sequences into the data set, neither spatial (Geneland) nor nonspatial (BAPS) genetic structuring analyses helped infer the Serbian population origin. However, the comparison of the retrieved COI haplotype with previously characterized mitogenomes indicated a temperate strain origin, capable of overwintering. Such findings suggest that the newly registered Ae. albopictus population could be able to establish itself since previous studies outlined Novi Sad as a suitable area.
Thyroid Hormone Regulates Developmental Titin Isoform Transitions via the Phosphatidylinositol-3-Kinase/ AKT Pathway

Titins, giant sarcomere proteins with major mechanical/signaling functions, are expressed in 2 main isoform classes in the mammalian heart: N2B (3000 kDa) and N2BA (>3200 kDa). A dramatic isoform switch occurs during cardiac development, from fetal N2BA titin (3700 kDa) expressed before birth to a mix of smaller N2BA/N2B isoforms found postnatally; adult rat hearts almost exclusively have N2B titin. The isoform switch, which can be reversed in chronic human heart failure, alters myocardial distensibility and mechanosignaling. Here we determined factors regulating this switch using, as a model system, primary cardiomyocyte cultures prepared from embryonic rats. In standard culture, the mean N2B percentage initially was 14% and increased by ≈60% within 1 week, resembling the in vivo switching. The titin isoform transition was independent of endothelin-1–induced myocyte hypertrophy and was not altered by pacing, contractile arrest, or cell stretch; however, it was modestly impaired by decreasing substrate rigidity and strongly dependent on serum components. Angiotensin II significantly promoted the transition. The mean N2B proportion in 1-week-old cultures dropped 20% to 25% in hormone-reduced medium, but addition of 3,5,3′-triiodo-l-thyronine (T3) nearly restored the proportion to that found in standard culture. This T3 effect was not prevented by bisphenol A, a specific inhibitor of the classic genomic pathway of T3 action. In contrast, the titin switch could be stalled by the phosphatidylinositol 3-kinase inhibitor LY294002, which decreased the proportion of N2B mRNA transcripts within hours and suppressed a rapid T3-induced increase in Akt phosphorylation. Also, angiotensin II, but not endothelin-1 or cell stretch, enhanced Akt phosphorylation. Thus, although matrix stiffness modulates developmental titin isoform transitions, these transitions are mainly regulated through phosphatidylinositol 3-kinase/Akt-dependent signaling triggered particularly by T3 via a rapid action pathway.
Robust Synthesis Method for Secure Directional Modulation With Imperfect Direction Angle

Directional modulation (DM) is a secure transmission technology that is able to retain the original constellation of transmitted signals along the desired direction, while distort the constellation in the undesired directions at the same time. In this letter, we develop novel and robust DM synthesis methods for enhancing the transmission performance. Specifically, we first propose a low-complexity dynamic DM synthesis method. In this method, we derive a closed-form expression for the null space of conjugate transpose of the steering vector in the desired direction. Based on the expression derived, we construct a projection matrix in order to form artificial noises to those undesired directions. Then, we focus our attention on more practical scenarios, where there is uncertainty in the estimated direction angle. This uncertainty will cause estimation errors and seriously jeopardize the receiving performance in the desired direction. To mitigate the uncertainty effect, we further propose a robust DM synthesis method based on conditional minimum mean square error. The proposed method aims to minimize the distortion of the constellation points along the desired direction. Simulation results show that our proposed robust DM method is capable of substantially improving the bit error rate performance compared with the state-of-the-art methods.
Online Spatial and Temporal Calibration for Monocular Direct Visual-Inertial Odometry

Owing to the nonlinearity in visual-inertial state estimation, sufficiently accurate initial states, especially the spatial and temporal parameters between IMU (Inertial Measurement Unit) and camera, should be provided to avoid divergence. Moreover, these parameters are required to be calibrated online since they are likely to vary once the mechanical configuration slightly changes. Recently, direct approaches have gained popularity for their better performance than feature-based approaches in little-texture or low-illumination environments, taking advantage of tracking pixels directly. Based on these considerations, we perform a direct version of monocular VIO (Visual-inertial Odometry), and propose a novel approach to initialize the spatial-temporal parameters and estimate them with all other variables of interest (IMU pose, point inverse depth, etc.). We highlight that our approach is able to perform robust and accurate initialization and online calibration for the spatial and temporal parameters without utilizing any prior information, and also achieves high-precision estimates even when large temporal offset occurs. The performance of the proposed approach was verified through the public UAV (Unmanned Aerial Vehicle) dataset.
Neurocognitive and functional outcomes in patients with diffuse frontal lower-grade gliomas undergoing intraoperative awake brain mapping.

OBJECTIVELower-grade gliomas (LGGs) are often observed within eloquent regions, which indicates that tumor resection in these areas carries a potential risk for neurological disturbances, such as motor deficit, language disorder, and/or neurocognitive impairments. Some patients with frontal tumors exhibit severe impairments of neurocognitive function, including working memory and spatial awareness, after tumor removal. The aim of this study was to investigate neurocognitive and functional outcomes of frontal LGGs in both the dominant and nondominant hemispheres after awake brain mapping.METHODSData from 50 consecutive patients with diffuse frontal LGGs in the dominant and nondominant hemispheres who underwent awake brain surgery between December 2012 and September 2018 were retrospectively analyzed. The goal was to map neurocognitive functions such as working memory by using working memory tasks, including digit span testing and N-back tasks.RESULTSDue to awake language mapping, the frontal aslant tract was frequently identified as a functional boundary in patients with left superior frontal gyrus tumors (76.5%). Furthermore, functional boundaries were identified while evaluating verbal and spatial working memory function by stimulating the dorsolateral prefrontal cortex using the digit span and visual N-back tasks in patients with right superior frontal gyrus tumors (7.1%). Comparing the preoperative and postoperative neuropsychological assessments from the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) and Wechsler Memory Scale-Revised (WMS-R), significant improvement following awake surgery was observed in mean Perceptual Organization (Z = -2.09, p = 0.04) in WAIS-III scores. Postoperative mean WMS-R scores for Visual Memory (Z = -2.12, p = 0.03) and Delayed Recall (Z = -1.98, p = 0.04) were significantly improved compared with preoperative values for every test after awake surgery. No significant deterioration was noted with regard to neurocognitive functions in a comprehensive neuropsychological test battery. In the postoperative course, early transient speech and motor disturbances were observed in 30.0% and 28.0% of patients, respectively. In contrast, late permanent speech and motor disturbances were observed in 0% and 4.0%, respectively.CONCLUSIONSIt is noteworthy that no significant postoperative deterioration was identified compared with preoperative status in a comprehensive neuropsychological assessment. The results demonstrated that awake functional mapping enabled favorable neurocognitive and functional outcomes after surgery in patients with diffuse frontal LGGs.
microRNA‐16‐5p‐containing exosomes derived from bone marrow‐derived mesenchymal stem cells inhibit proliferation, migration, and invasion, while promoting apoptosis of colorectal cancer cells by downregulating ITGA2

Colorectal cancer (CRC) is a form of cancer developing from either the colon or rectum. Nowadays, research supports the functionality of exosome expressing microRNAs (miRNAs) as potential biomarker for various cancers including CRC. This study was performed with the intent of investigating the roles of both bone marrow‐derived mesenchymal stem cells (BMSCs) and exosomal miR‐16‐5p in CRC by regulating integrin α2 (ITGA2). A microarray‐based analysis was conducted to screen the CRC‐associated differentially expressed genes (DEGs) as well as potential regulatory miRNAs. Next, the role of miR‐16‐5p in terms of its progression in association with CRC was determined. Subsequently, CRC cells were exposed to exosomes secreted by BMSCs transfected with miR‐16‐5p, isolated and cocultured with CRC cells in an attempt to identify the role of exosomes. Effects of BMSCs‐derived exosomes overexpressing miR‐16‐5p on biological functions of CRC cells and tumorigenicity were all subsequently detected. Effects of miR‐16‐5p treated with CRC cells in regard to CRC in vivo were also measured. ITGA2 was overexpressed, while miR‐16‐5p was poorly expressed in CRC cells and miR‐16‐5p targeted ITGA2. The in vitro experiments revealed that the BMSCs‐derived exosomes overexpressing miR‐16‐5p inhibited proliferation, migration, and invasion, while simultaneously stimulating the apoptosis of the CRC cells via downregulation of ITGA2. Furthermore, the results of in vivo experiments confirmed that the BMSCs‐derived exosomes overexpressing miR‐16‐5p repressed the tumor growth of CRC. Collectively, BMSCs‐derived exosomes overexpressing miR‐16‐5p restricted the progression of CRC by downregulating ITGA2.
Effects of Cycling on Subsequent Running Performance, Stride Length, and Muscle Oxygen Saturation in Triathletes

Running performance is a determinant factor for victory in Sprint and Olympic distance triathlon. Previous cycling may impair running performance in triathlons, so brick training becomes an important part of training. Wearable technology that is used by triathletes can offer several metrics for optimising training in real-time. The aim of this study was to analyse the effect of previous cycling on subsequent running performance in a field test, while using kinematics metrics and SmO2 provided by wearable devices that are potentially used by triathletes. Ten trained triathletes participated in a randomised crossover study, performing two trial sessions that were separated by seven days: the isolated run trial (IRT) and the bike-run trial (BRT). Running kinematics, physiological outcomes, and perceptual parameters were assessed before and after each running test. The running distance was significantly lower in the BRT when compared to the IRT, with a decrease in stride length of 0.1 m (p = 0.00) and higher %SmO2 (p = 0.00) in spite of the maximal intensity of exercise. No effects were reported in vertical oscillation, ground contact time, running cadence, and average heart rate. These findings may only be relevant to ‘moderate level’ triathletes, but not to ‘elite’ ones. Triathletes might monitor their %SmO2 and stride length during brick training and then compare it with isolated running to evaluate performance changes. Using wearable technology (near-infrared spectroscopy, accelerometry) for specific brick training may be a good option for triathletes.