bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biopsy-free in vivo virtual histology of skin using deep learning
Authors: Li Jingxi , Garfinkel Jason , Zhang Xiaoran , Wu Di , Zhang Yijie , de Haan Kevin , Wang Hongda , Liu Tairan , Bai Bijie , Rivenson Yair , Rubinstein Gennady , Scumpia Philip O. , Ozcan Aydogan 
Published: November 2021

AbstractAn invasive biopsy followed by histological staining is the benchmark for pathological diagnosis of skin tumors. The process is cumbersome and time-consuming, often leading to unnecessary biopsies and scars. Emerging noninvasive optical technologies such as reflectance confocal microscopy (RCM) can provide label-free, cellular-level resolution, in vivo images of skin without performing a biopsy. Although RCM is a useful diagnostic tool, it requires specialized training because the acquired images are grayscale, lack nuclear features, and are difficult to correlate with tissue pathology. Here, we present a deep learning-based framework that uses a convolutional neural network to rapidly transform in vivo RCM images of unstained skin into virtually-stained hematoxylin and eosin-like images with microscopic resolution, enabling visualization of the epidermis, dermal-epidermal junction, and superficial dermis layers. The network was trained under an adversarial learning scheme, which takes ex vivo RCM images of excised unstained/label-free tissue as inputs and uses the microscopic images of the same tissue labeled with acetic acid nuclear contrast staining as the ground truth. We show that this trained neural network can be used to rapidly perform virtual histology of in vivo, label-free RCM images of normal skin structure, basal cell carcinoma, and melanocytic nevi with pigmented melanocytes, demonstrating similar histological features to traditional histology from the same excised tissue. This application of deep learning-based virtual staining to noninvasive imaging technologies may permit more rapid diagnoses of malignant skin neoplasms and reduce invasive skin biopsies.
A multi-modal MRI analysis of brain structure and function in relation to OXT methylation in maltreated children and adolescents
Authors: Nishitani Shota , Fujisawa Takashi X. , Hiraoka Daiki , Makita Kai , Takiguchi Shinichiro , Hamamura Shoko , Yao Akiko , Shimada Koji , Smith Alicia K. , Tomoda Akemi 
Published: November 2021

AbstractChild maltreatment dysregulates the brain’s oxytocinergic system, resulting in dysfunctional attachment patterns. However, how the oxytocinergic system in children who are maltreated (CM) is epigenetically affected remains unknown. We assessed differences in salivary DNA methylation of the gene encoding oxytocin (OXT) between CM (n = 24) and non-CM (n = 31), alongside its impact on brain structures and functions using multi-modal brain imaging (voxel-based morphometry, diffusion tensor imaging, and task and resting-state functional magnetic resonance imaging). We found that CM showed higher promoter methylation than non-CM, and nine CpG sites were observed to be correlated with each other and grouped into one index (OXTmi). OXTmi was significantly negatively correlated with gray matter volume (GMV) in the left superior parietal lobule (SPL), and with right putamen activation during a rewarding task, but not with white matter structures. Using a random forest regression model, we investigated the sensitive period and type of maltreatment that contributed the most to OXTmi in CM, revealing that they were 5–8 years of age and physical abuse (PA), respectively. However, the presence of PA (PA+) was meant to reflect more severe cases, such as prolonged exposure to multiple types of abuse, than the absence of PA. PA+ was associated with significantly greater functional connectivity between the right putamen set as the seed and the left SPL and the left cerebellum exterior. The results suggest that OXT promoter hypermethylation may lead to the atypical development of reward and visual association structures and functions, thereby potentially worsening clinical aspects raised by traumatic experiences.
Inhibition of DTYMK significantly restrains the growth of HCC and increases sensitivity to oxaliplatin
Authors: Sun Fengze , Liu Yuanyuan , Gong Tingting , Pan Qiuzhong , Xiang Tong , Zhao Jingjing , Tang Yan , Chen Hao , Han Yulong , Song Mengjia , Huang Yue , Li Han , Chen Yuanyuan , Yang Chaopin , Yang Jieying , Wang Qijing , Li Yongqiang , He Jia , Weng Desheng , Peng Ruiqing , Xia Jianchuan 
Published: November 2021

AbstractMost patients with hepatocellular carcinoma (HCC) are in the middle or advanced stage at the time of diagnosis, and the therapeutic effect is limited. Therefore, this study aimed to verify whether deoxythymidylate kinase (DTYMK) increased in HCC and was an effective therapeutic target in HCC. The findings revealed that the DTYMK level significantly increased and correlated with poor prognosis in HCC. However, nothing else is known, except that DTYMK could catalyze the phosphorylation of deoxythymidine monophosphate (dTMP) to form deoxythymidine diphosphate (dTDP). A number of experiments were performed to study the function of DTYMK in vitro and in vivo to resolve this knowledge gap. The knockdown of DTYMK was found to significantly inhibit the growth of HCC and increase the sensitivity to oxaliplatin, which is commonly used in HCC treatment. Moreover, DTYMK was found to competitively combine with miR-378a-3p to maintain the expression of MAPK activated protein kinase 2 (MAPKAPK2) and thus activate the phospho-heat shock protein 27 (phospho-HSP27)/nuclear factor NF-kappaB (NF-κB) axis, which mediated the drug resistance, proliferation of tumor cells, and infiltration of tumor-associated macrophages by inducing the expression of C-C motif chemokine ligand 5 (CCL5). Thus, this study demonstrated a new mechanism and provided a new insight into the role of mRNA in not only encoding proteins to regulate the process of life but also regulating the expression of other genes and tumor microenvironment through the competing endogenous RNA (ceRNA) mechanism.
Molecular and histological traits of reduced lysosomal acid lipase activity in the fatty liver
Authors: Carotti Simone , Lettieri-Barbato Daniele , Piemonte Fiorella , Ruggiero Sergio , Rosina Marco , Zalfa Francesca , Zingariello Maria , Arciprete Francesca , Valentini Francesco , Francesconi Maria , D’Amico Jessica , De Vincentis Antonio , Baiocchini Andrea , Perrone Giuseppe , Antonelli-Incalzi Raffaele , Morini Sergio , Picardi Antonio , Aquilano Katia , Vespasiani-Gentilucci Umberto 
Published: November 2021

AbstractRecent studies demonstrated reduced blood lysosomal acid lipase (LAL) activity in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to verify hepatic LAL protein content and activity in in vitro and in vivo models of fat overload and in NAFLD patients. LAL protein content and activity were firstly evaluated in Huh7 cells exposed to high-glucose/high-lipid (HGHL) medium and in the liver of C57BL/6 mice fed with high-fat diet (HFD) for 4 and 8 months. LAL protein was also evaluated by immunohistochemistry in liver biopsies from 87 NAFLD patients and 10 controls, and correlated with hepatic histology. Huh7 cells treated with HGHL medium showed a significant reduction of LAL activity, which was consistent with reduced LAL protein levels by western blotting using an antibody towards the N-term of the enzyme. Conversely, antibodies towards the C-term of the enzyme evidenced LAL accumulation, suggesting a post-translational modification that masks the LAL N-term epitope and affects enzymatic activity. Indeed, we found a high rate of ubiquitination and extra-lysosomal localization of LAL protein in cells treated with HGHL medium. Consistent with these findings, inhibition of proteasome triggered dysfunctional LAL accumulation and affected LAL activity. Accumulation of ubiquitinated/dysfunctional LAL was also found in the liver of HFD fed mice. In NAFLD patients, hepatic levels of non-ubiquitinated/functional LAL were lower than in controls and inversely correlated with disease activity and some of the hallmarks of reduced LAL. Fat overload leads to LAL ubiquitination and impairs its function, possibly reducing hepatic fat disposal and promoting NAFLD activity.
Giant field-like torque by the out-of-plane magnetic spin Hall effect in a topological antiferromagnet
Authors: Kondou Kouta , Chen Hua , Tomita Takahiro , Ikhlas Muhammad , Higo Tomoya , MacDonald Allan H. , Nakatsuji Satoru , Otani YoshiChika 
Published: November 2021

AbstractSpin-orbit torques (SOT) enable efficient electrical control of the magnetic state of ferromagnets, ferrimagnets and antiferromagnets. However, the conventional SOT has severe limitation that only in-plane spins accumulate near the surface, whether interpreted as a spin Hall effect (SHE) or as an Edelstein effect. Such a SOT is not suitable for controlling perpendicular magnetization, which would be more beneficial for realizing low-power-consumption memory devices. Here we report the observation of a giant magnetic-field-like SOT in a topological antiferromagnet Mn3Sn, whose direction and size can be tuned by changing the order parameter direction of the antiferromagnet. To understand the magnetic SHE (MSHE)- and the conventional SHE-induced SOTs on an equal footing, we formulate them as interface spin-electric-field responses and analyzed using a macroscopic symmetry analysis and a complementary microscopic quantum kinetic theory. In this framework, the large out-of-plane spin accumulation due to the MSHE has an inter-band origin and is likely to be caused by the large momentum-dependent spin splitting in Mn3Sn. Our work demonstrates the unique potential of antiferromagnetic Weyl semimetals in overcoming the limitations of conventional SOTs and in realizing low-power spintronics devices with new functionalities.
Dynamic transformation of cubic copper catalysts during CO2 electroreduction and its impact on catalytic selectivity
Authors: Grosse Philipp , Yoon Aram , Rettenmaier Clara , Herzog Antonia , Chee See Wee , Roldan Cuenya Beatriz 
Published: November 2021

AbstractTo rationally design effective and stable catalysts for energy conversion applications, we need to understand how they transform under reaction conditions and reveal their underlying structure-property relationships. This is especially important for catalysts used in the electroreduction of carbon dioxide where product selectivity is sensitive to catalyst structure. Here, we present real-time electrochemical liquid cell transmission electron microscopy studies showing the restructuring of copper(I) oxide cubes during reaction. Fragmentation of the solid cubes, re-deposition of new nanoparticles, catalyst detachment and catalyst aggregation are observed as a function of the applied potential and time. Using cubes with different initial sizes and loading, we further correlate this dynamic morphology with the catalytic selectivity through time-resolved scanning electron microscopy measurements and product analysis. These comparative studies reveal the impact of nanoparticle re-deposition and detachment on the catalyst reactivity, and how the increased surface metal loading created by re-deposited nanoparticles can lead to enhanced C2+ selectivity and stability.
Asymmetric radical carboesterification of dienes
Authors: Zhu Xiaotao , Jian Wujun , Huang Meirong , Li Daliang , Li Yajun , Zhang Xinhao , Bao Hongli 
Published: November 2021

AbstractThe straightforward strategy of building a chiral C-O bond directly on a general carbon radical center is challenging and stereocontrol of the reactions of open-chain hydrocarbon radicals remains a largely unsolved problem. Advance in this elementary step will spur the development of asymmetric radical C-O bond construction. Herein, we report a copper-catalyzed regioselective and enantioselective carboesterification of substituted dienes using alkyl diacyl peroxides as the source of both the carbon and oxygen substituents. The participation of external acids in this reaction substantially extends its applicability and leads to structurally diverse allylic ester products. This work represents the advance in the key elementary reaction of intermolecular enantioselective construction of C-O bond on open-chain hydrocarbon radicals and may lead to the discovery of other asymmetric radical reactions.
Genetic fusions favor tumorigenesis through degron loss in oncogenes
Authors: Liu Jing , Tokheim Collin , Lee Jonathan D. , Gan Wenjian , North Brian J. , Liu X. Shirley , Pandolfi Pier Paolo , Wei Wenyi 
Published: November 2021

AbstractChromosomal rearrangements can generate genetic fusions composed of two distinct gene sequences, many of which have been implicated in tumorigenesis and progression. Our study proposes a model whereby oncogenic gene fusions frequently alter the protein stability of the resulting fusion products, via exchanging protein degradation signal (degron) between gene sequences. Computational analyses of The Cancer Genome Atlas (TCGA) identify 2,406 cases of degron exchange events and reveal an enrichment of oncogene stabilization due to loss of degrons from fusion. Furthermore, we identify and experimentally validate that some recurrent fusions, such as BCR-ABL, CCDC6-RET and PML-RARA fusions, perturb protein stability by exchanging internal degrons. Likewise, we also validate that EGFR or RAF1 fusions can be stabilized by losing a computationally-predicted C-terminal degron. Thus, complementary to enhanced oncogene transcription via promoter swapping, our model of degron loss illustrates another general mechanism for recurrent fusion proteins in driving tumorigenesis.
Synchronized multi-wavelength soliton fiber laser via intracavity group delay modulation
Authors: Mao Dong , Wang Huaqiang , Zhang Heze , Zeng Chao , Du Yueqing , He Zhiwen , Sun Zhipei , Zhao Jianlin 
Published: November 2021

AbstractLocking of longitudinal modes in laser cavities is the common path to generate ultrashort pulses. In traditional multi-wavelength mode-locked lasers, the group velocities rely on lasing wavelengths due to the chromatic dispersion, yielding multiple trains of independently evolved pulses. Here, we show that mode-locked solitons at different wavelengths can be synchronized inside the cavity by engineering the intracavity group delay with a programmable pulse shaper. Frequency-resolved measurements fully retrieve the fine temporal structure of pulses, validating the direct generation of synchronized ultrafast lasers from two to five wavelengths with sub-pulse repetition-rate up to ~1.26 THz. Simulation results well reproduce and interpret the key experimental phenomena, and indicate that the saturable absorption effect automatically synchronize multi-wavelength solitons in despite of the small residual group delay difference. These results demonstrate an effective approach to create synchronized complex-structure solitons, and offer an effective platform to study the evolution dynamics of nonlinear wavepackets.
Smooth muscle-specific MMP17 (MT4-MMP) regulates the intestinal stem cell niche and regeneration after damage
Authors: Martín-Alonso Mara , Iqbal Sharif , Vornewald Pia M. , Lindholm Håvard T. , Damen Mirjam J. , Martínez Fernando , Hoel Sigrid , Díez-Sánchez Alberto , Altelaar Maarten , Katajisto Pekka , Arroyo Alicia G. , Oudhoff Menno J. 
Published: November 2021

AbstractSmooth muscle is an essential component of the intestine, both to maintain its structure and produce peristaltic and segmentation movements. However, very little is known about other putative roles that smooth muscle cells may have. Here, we show that smooth muscle cells may be the dominant suppliers of BMP antagonists, which are niche factors essential for intestinal stem cell maintenance. Furthermore, muscle-derived factors render epithelium reparative and fetal-like, which includes heightened YAP activity. Mechanistically, we find that the membrane-bound matrix metalloproteinase MMP17, which is exclusively expressed by smooth muscle cells, is required for intestinal epithelial repair after inflammation- or irradiation-induced injury. Furthermore, we propose that MMP17 affects intestinal epithelial reprogramming after damage indirectly by cleaving diffusible factor(s) such as the matricellular protein PERIOSTIN. Together, we identify an important signaling axis that establishes a role for smooth muscle cells as modulators of intestinal epithelial regeneration and the intestinal stem cell niche.
Global predictions of primary soil salinization under changing climate in the 21st century
Authors: Hassani Amirhossein , Azapagic Adisa , Shokri Nima 
Published: November 2021

AbstractSoil salinization has become one of the major environmental and socioeconomic issues globally and this is expected to be exacerbated further with projected climatic change. Determining how climate change influences the dynamics of naturally-occurring soil salinization has scarcely been addressed due to highly complex processes influencing salinization. This paper sets out to address this long-standing challenge by developing data-driven models capable of predicting primary (naturally-occurring) soil salinity and its variations in the world’s drylands up to the year 2100 under changing climate. Analysis of the future predictions made here identifies the dryland areas of South America, southern and western Australia, Mexico, southwest United States, and South Africa as the salinization hotspots. Conversely, we project a decrease in the soil salinity of the drylands in the northwest United States, the Horn of Africa, Eastern Europe, Turkmenistan, and west Kazakhstan in response to climate change over the same period.
A Mycobacterium tuberculosis-specific subunit vaccine that provides synergistic immunity upon co-administration with Bacillus Calmette-Guérin
Authors: Woodworth Joshua S. , Clemmensen Helena Strand , Battey Hannah , Dijkman Karin , Lindenstrøm Thomas , Laureano Raquel Salvador , Taplitz Randy , Morgan Jeffrey , Aagaard Claus , Rosenkrands Ida , Lindestam Arlehamn Cecilia S. , Andersen Peter , Mortensen Rasmus 
Published: November 2021

AbstractGiven the encouraging clinical results of both candidate subunit vaccines and revaccination with Bacillus Calmette-Guérin (BCG) against tuberculosis (TB), there is support for combining BCG and subunit vaccination for increased efficacy. BCG and Mycobacterium tuberculosis (Mtb) share ~98% of their genome and current subunit vaccines are almost exclusively designed as BCG boosters. The goal of this study is to design a TB subunit vaccine composed of antigens not shared with BCG and explore the advantages of this design in a BCG + subunit co-administration vaccine strategy. Eight protective antigens are selected to create an Mtb-specific subunit vaccine, named H107. Whereas traditional vaccines containing BCG-shared antigens exhibit in vivo cross-reactivity to BCG, H107 shows no cross-reactivity and does not inhibit BCG colonization. Instead, co-administering H107 with BCG leads to increased adaptive responses against both H107 and BCG. Importantly, rather than expanding BCG-primed T cells, H107 broadens the overall vaccine repertoire with new T cell clones and introduces ‘adjuvant-imprinted’ qualities including Th17 responses and less-differentiated Th1 cells. Collectively, these features of H107 are associated with a substantial increase in long-term protection.
Age-seroprevalence curves for the multi-strain structure of influenza A virus
Authors: Vinh Dao Nguyen , Nhat Nguyen Thi Duy , de Bruin Erwin , Vy Nguyen Ha Thao , Thao Tran Thi Nhu , Phuong Huynh Thi , Anh Pham Hong , Todd Stacy , Quan Tran Minh , Thanh Nguyen Thi Le , Lien Nguyen Thi Nam , Ha Nguyen Thi Hong , Hong Tran Thi Kim , Thai Pham Quang , Choisy Marc , Nguyen Tran Dang , Simmons Cameron P. , Thwaites Guy E. , Clapham Hannah E. , Chau Nguyen Van Vinh , Koopmans Marion , Boni Maciej F. 
Published: November 2021

AbstractThe relationship between age and seroprevalence can be used to estimate the annual attack rate of an infectious disease. For pathogens with multiple serologically distinct strains, there is a need to describe composite exposure to an antigenically variable group of pathogens. In this study, we assay 24,402 general-population serum samples, collected in Vietnam between 2009 to 2015, for antibodies to eleven human influenza A strains. We report that a principal components decomposition of antibody titer data gives the first principal component as an appropriate surrogate for seroprevalence; this results in annual attack rate estimates of 25.6% (95% CI: 24.1% – 27.1%) for subtype H3 and 16.0% (95% CI: 14.7% – 17.3%) for subtype H1. The remaining principal components separate the strains by serological similarity and associate birth cohorts with their particular influenza histories. Our work shows that dimensionality reduction can be used on human antibody profiles to construct an age-seroprevalence relationship for antigenically variable pathogens.
Identifying regulators of parental imprinting by CRISPR/Cas9 screening in haploid human embryonic stem cells
Authors: Bar Shiran , Vershkov Dan , Keshet Gal , Lezmi Elyad , Meller Naama , Yilmaz Atilgan , Yanuka Ofra , Nissim-Rafinia Malka , Meshorer Eran , Eldar-Geva Talia , Benvenisty Nissim 
Published: November 2021

AbstractIn mammals, imprinted genes are regulated by differentially methylated regions (DMRs) that are inherited from germ cells, leading to monoallelic expression in accordance with parent-of-origin. Yet, it is largely unknown how imprinted DMRs are maintained in human embryos despite global DNA demethylation following fertilization. Here, we explored the mechanisms involved in imprinting regulation by employing human parthenogenetic embryonic stem cells (hpESCs), which lack paternal alleles. We show that although global loss of DNA methylation in hpESCs affects most imprinted DMRs, many paternally-expressed genes (PEGs) remain repressed. To search for factors regulating PEGs, we performed a genome-wide CRISPR/Cas9 screen in haploid hpESCs. This revealedATF7IPas an essential repressor of a set of PEGs, which we further show is also required for silencing sperm-specific genes. Our study reinforces an important role for histone modifications in regulating imprinted genes and suggests a link between parental imprinting and germ cell identity.
Enhanced gyrotropic birefringence and natural optical activity on electromagnon resonance in a helimagnet
Authors: Iguchi S. , Masuda R. , Seki S. , Tokura Y. , Takahashi Y. 
Published: November 2021

AbstractSpontaneous symmetry breaking in crystalline solid often produces exotic nonreciprocal phenomena. As one such example, the unconventional optical rotation with nonreciprocity, which is termed gyrotropic birefringence, is expected to emerge from the magnetoelectric coupling. However, the fundamental nature of gyrotropic birefringence remains to be examined. Here w`e demonstrate the gyrotropic birefringence enhanced by the dynamical magnetoelectric coupling on the electrically active magnon resonance, i.e. electromagnon, in a multiferroic helimagnet. The helical spin order having both polarity and chirality is found to cause the giant gyrotropic birefringence in addition to the conventional gyrotropy, i.e. natural optical activity. It is demonstrated that the optical rotation of gyrotropic birefringence can be viewed as the nonreciprocal rotation of the optical principal axes, while the crystallographic and magnetic anisotropies are intact. The independent control of the nonreciprocal linear (gyrotropic birefringence) and circular (natural optical activity) birefringence/dichroism paves a way for the optically active devices.