bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial augmentation of CD34+ cells from healthy donors and patients with mitochondrial DNA disorders confers functional benefit
Authors: Jacoby Elad , Ben Yakir-Blumkin Moriya , Blumenfeld-Kan Shiri , Brody Yehuda , Meir Amilia , Melamed-Book Naomi , Napso Tina , Pozner Gat , Saadi Esraa , Shabtay-Orbach Ayelet , Yivgi-Ohana Natalie , Sher Noa , Toren Amos 
Published: October 2021

AbstractMitochondria are cellular organelles critical for numerous cellular processes and harboring their own circular mitochondrial DNA (mtDNA). Most mtDNA associated disorders (either deletions, mutations, or depletion) lead to multisystemic disease, often severe at a young age, with no disease-modifying therapies. Mitochondria have a capacity to enter eukaryotic cells and to be transported between cells. We describe a method of ex vivo augmentation of hematopoietic stem and progenitor cells (HSPCs) with normal exogenous mitochondria, termed mitochondrial augmentation therapy (MAT). Here, we show that MAT is feasible and dose dependent, and improves mitochondrial content and oxygen consumption of healthy and diseased HSPCs. Ex vivo mitochondrial augmentation of HSPCs from a patient with a mtDNA disorder leads to superior human engraftment in a non-conditioned NSGS mouse model. Using a syngeneic mouse model of accumulating mitochondrial dysfunction (Polg), we show durable engraftment in non-conditioned animals, with in vivo transfer of mitochondria to recipient hematopoietic cells. Taken together, this study supports MAT as a potential disease-modifying therapy for mtDNA disorders.
Don’t get it or don’t spread it: comparing self-interested versus prosocial motivations for COVID-19 prevention behaviors
Authors: Jordan Jillian J. , Yoeli Erez , Rand David G. 
Published: October 2021

AbstractCOVID-19 prevention behaviors may be seen as self-interested or prosocial. Using American samples from MTurk and Prolific (total n = 6850), we investigated which framing is more effective—and motivation is stronger—for fostering prevention behavior intentions. We evaluated messaging that emphasized personal, public, or personal and public benefits of prevention. In initial studies (conducted March 14–16, 2020), the Public treatment was more effective than the Personal treatment, and no less effective than the Personal + Public treatment. In additional studies (conducted April 17–30, 2020), all three treatments were similarly effective. Across all these studies, the perceived public threat of coronavirus was also more strongly associated with prevention intentions than the perceived personal threat. Furthermore, people who behaved prosocially in incentivized economic games years before the pandemic had greater prevention intentions. Finally, in a field experiment (conducted December 21–23, 2020), we used our three messaging strategies to motivate contact-tracing app signups (n = 152,556 newsletter subscribers). The design of this experiment prevents strong causal inference; however, the results provide suggestive evidence that the Personal + Public treatment may have been more effective than the Personal or Public treatment. Together, our results highlight the importance of prosocial motives for COVID-19 prevention.
A high temporal/spatial resolution neuro-architecture study of rodent brain by wideband echo planar imaging
Authors: Cheng Po-Wei , Chiueh Tzi-Dar , Chen Jyh-Horng 
Published: October 2021

AbstractLatest simultaneous multi-slice (SMS) methods greatly benefit MR efficiency for recent studies using parallel imaging technique. However, these methods are limited by the requirement of array coils. The proposed Coherent Wideband method, which employs an extended field of view to separate multiple excited slices, can be applied to any existing MRI instrument, even those without array coils. In this study, the Coherent Wideband echo-planar imaging method was implemented on 7 T animal MRI to exhibit comprehensive enhancements in neuro-architecture, including diffusion tensor imaging (DTI) and functional MR studies (fMRI). Under the same scan time, the time-saving effect can be manipulated to increase the number of averages for DTI SNR improvement, reducing fractional anisotropy difference by 56.9% (from 0.072 to 0.041) and the deviation angle by 64% (from 25.3° to 16.2°). In summary, Coherent Wideband Echo Planar Imaging (EPI) will provide faster, higher resolution, thinner slice, or higher SNR imaging for precision neuro-architecture studies.
Association between Fusobacterium nucleatum and patient prognosis in metastatic colon cancer
Authors: Lee Jii Bum , Kim Kyung-A , Cho Ho Yeon , Kim DooA , Kim Won Kyu , Yong Dongeun , Lee Hyukmin , Yoon Sang Sun , Han Dai Hoon , Han Yoon Dae , Paik Soonmyung , Jang Mi , Kim Han Sang , Ahn Joong Bae 
Published: October 2021

AbstractRecent evidence suggests that Fusobacterium nucleatum (Fn) is associated with the development and progression of colorectal cancer. We aimed to delineate the clinical implications of Fn in metastatic colon cancer. We performed quantitative polymerase chain reaction (qPCR) using DNA samples from synchronous metastatic colon cancer patients with either formalin-fixed paraffin-embedded (FFPE) archival primary site tumor samples or fresh colon tissues. Progression-free survival (PFS)1 and PFS2 were defined as PFS of first- and second-line palliative settings. qPCR for Fn was successfully performed using 112 samples (FFPE, n = 61; fresh tissue, n = 51). Forty-one and 68 patients had right-sided and left-sided colon cancer, respectively. Patients with Fn enriched right-sided colon cancers had shorter PFS1 (9.7 vs. 11.2 months) than the other subgroups (HR 3.54, 95% confidence interval [CI] 1.05–11.99; P = 0.04). Fn positive right-sided colon was also associated with shorter PFS2 (3.7 vs. 6.7 months; HR 2.34, 95% CI 0.69–7.91; P = 0.04). In the univariate analysis, PFS1 was affected by differentiation and Fn positive right-sided colon cancer. The multivariate analysis showed that differentiation (HR 2.68, 95% CI 1.40–5.14, P = 0.01) and Fn positive right-sided colon (HR 0.40, 95% CI 0.18–0.88, P = 0.02) were associated with PFS1. Fn enrichment in right sided colon was not associated with overall survival (OS). Fn enrichment has significantly worse prognosis in terms of PFS1 and PFS2 in patients with right-sided metastatic colon cancers.
Development and validation of a neural network for NAFLD diagnosis
Authors: Sorino Paolo , Campanella Angelo , Bonfiglio Caterina , Mirizzi Antonella , Franco Isabella , Bianco Antonella , Caruso Maria Gabriella , Misciagna Giovanni , Aballay Laura R. , Buongiorno Claudia , Liuzzi Rosalba , Cisternino Anna Maria , Notarnicola Maria , Chiloiro Marisa , Fallucchi Francesca , Pascoschi Giovanni , Osella Alberto Rubén 
Published: October 2021

AbstractNon-Alcoholic Fatty Liver Disease (NAFLD) affects about 20–30% of the adult population in developed countries and is an increasingly important cause of hepatocellular carcinoma. Liver ultrasound (US) is widely used as a noninvasive method to diagnose NAFLD. However, the intensive use of US is not cost-effective and increases the burden on the healthcare system. Electronic medical records facilitate large-scale epidemiological studies and, existing NAFLD scores often require clinical and anthropometric parameters that may not be captured in those databases. Our goal was to develop and validate a simple Neural Network (NN)-based web app that could be used to predict NAFLD particularly its absence. The study included 2970 subjects; training and testing of the neural network using a train–test-split approach was done on 2869 of them. From another population consisting of 2301 subjects, a further 100 subjects were randomly extracted to test the web app. A search was made to find the best parameters for the NN and then this NN was exported for incorporation into a local web app. The percentage of accuracy, area under the ROC curve, confusion matrix, Positive (PPV) and Negative Predicted Value (NPV) values, precision, recall and f1-score were verified. After that, Explainability (XAI) was analyzed to understand the diagnostic reasoning of the NN. Finally, in the local web app, the specificity and sensitivity values were checked. The NN achieved a percentage of accuracy during testing of 77.0%, with an area under the ROC curve value of 0.82. Thus, in the web app the NN evidenced to achieve good results, with a specificity of 1.00 and sensitivity of 0.73. The described approach can be used to support NAFLD diagnosis, reducing healthcare costs. The NN-based web app is easy to apply and the required parameters are easily found in healthcare databases.
Direct-current generators based on conductive polymers for self-powered flexible devices
Authors: Meng Yanfang , Zhang Long , Xu Guangyuan , Wang Heling 
Published: October 2021

AbstractDirect-current generators, especially those based on the Schottky contacts between conductive polymers and metal electrodes, are efficient in converting mechanical stimuli into electrical energy. In contrast to triboelectric and piezoelectric generators, direct-current generators readily produce direct-current outputs and high currents that are crucial for integrating multiple energy-harvesting units in large scale and driving some types of devices. We are focusing on the relationship between Schottky barrier height and performance, systematically investigating the effects of various conductive polymers and electrodes on the outputs by both theoretical simulation and experiments. Tailoring the Schottky barrier height between conductive polymers and metal electrodes is demonstrated a significant approach to design the new DC generators. The preparation method of electrochemical deposition endows the generators flexibility, the linear relationship of current/voltage output vs. strain applied on the generators, combined with the large outputs offer advantages for the generator to work as flexible sensors. Furthermore, a mechanosensation-active matrix array based on direct-current generator for the strain monitoring demonstrated its promising prospects in flexible electronics. The direct-current generators with improved performance could serve as a stream new blood for versatile sensory systems and human–machine interactive interfaces.
In vivo study of light-driven naproxen release from gated mesoporous silica drug delivery system
Authors: Almáši Miroslav , Matiašová Anna Alexovič , Šuleková Monika , Beňová Eva , Ševc Juraj , Váhovská Lucia , Lisnichuk Maksym , Girman Vladimír , Zeleňáková Adriana , Hudák Alexander , Zeleňák Vladimír 
Published: October 2021

AbstractA drug delivery system based on mesoporous particles MCM-41 was post-synthetically modified by photo-sensitive ligand, methyl-(2E)-3-(4-(triethoxysilyl)-propoxyphenyl)-2-propenoate (CA) and the pores of MCM-41 particles were loaded with Naproxen sodium salt (NAP). The CA was used as a photoactive molecule that can undergo a reversible photo-dimerization by [2π + 2π] cycloaddition when irradiated with UV light of specific wavelengths. Thus, it has a function of gate-keeper that is responsible for opening/closing the pores and minimizing premature release of NAP. The physicochemical properties of the prepared system were studied by infrared spectroscopy (IR), nitrogen adsorption measurements, thermogravimetric analysis (TGA), scanning transmission electron microscopy (STEM) and energy dispersive X-ray spectroscopy (EDX). The mechanism of the opening/closing pores was confirmed by UV measurements. In vitro and in vivo drug release experiments and the concentration of released NAP was determined by UV spectroscopy and high-performance liquid chromatography (HPLC). In vivo drug release in the blood circulatory system of rats has demonstrated the effective photo-cleavage reaction of CA molecules after UV-light stimulation. The localization and morphological changes of the particles were studied in the blood and liver of rats at different time intervals. The particles in the blood have been shown to retain their original rod-like shape, and the particles in the liver have been hydrolysed, which has resulted in spherical shape with a reduced size.
A pyramidal deep learning pipeline for kidney whole-slide histology images classification
Authors: Abdeltawab Hisham , Khalifa Fahmi , Ghazal Mohammed , Cheng Liang , Gondim Dibson , El-Baz Ayman 
Published: October 2021

AbstractRenal cell carcinoma is the most common type of kidney cancer. There are several subtypes of renal cell carcinoma with distinct clinicopathologic features. Among the subtypes, clear cell renal cell carcinoma is the most common and tends to portend poor prognosis. In contrast, clear cell papillary renal cell carcinoma has an excellent prognosis. These two subtypes are primarily classified based on the histopathologic features. However, a subset of cases can a have a significant degree of histopathologic overlap. In cases with ambiguous histologic features, the correct diagnosis is dependent on the pathologist’s experience and usage of immunohistochemistry. We propose a new method to address this diagnostic task based on a deep learning pipeline for automated classification. The model can detect tumor and non-tumoral portions of kidney and classify the tumor as either clear cell renal cell carcinoma or clear cell papillary renal cell carcinoma. Our framework consists of three convolutional neural networks and the whole slide images of kidney which were divided into patches of three different sizes for input into the networks. Our approach can provide patchwise and pixelwise classification. The kidney histology images consist of 64 whole slide images. Our framework results in an image map that classifies the slide image on the pixel-level. Furthermore, we applied generalized Gauss-Markov random field smoothing to maintain consistency in the map. Our approach classified the four classes accurately and surpassed other state-of-the-art methods, such as ResNet (pixel accuracy: 0.89 Resnet18, 0.92 proposed). We conclude that deep learning has the potential to augment the pathologist’s capabilities by providing automated classification for histopathological images.
Structural, magnetic, and magnetocaloric properties of R2NiMnO6 (R = Eu, Gd, Tb)
Authors: Shinde K. P. , Lee E. J. , Manawan M. , Lee A. , Park S.-Y. , Jo Y. , Ku K. , Kim J. M. , Park J. S. 
Published: October 2021

AbstractThe crystal structure, cryogenic magnetic properties, and magnetocaloric performance of double perovskite Eu2NiMnO6 (ENMO), Gd2NiMnO6 (GNMO), and Tb2NiMnO6 (TNMO) ceramic powder samples synthesized by solid-state method have been investigated. X-ray diffraction structural investigation reveal that all compounds crystallize in the monoclinic structure with a P21/n space group. A ferromagnetic to paramagnetic (FM-PM) second-order phase transition occurred in ENMO, GNMO, and TNMO at 143, 130, and 112 K, respectively. Maximum magnetic entropy changes and relative cooling power with a 5 T applied magnetic field are determined to be 3.2, 3.8, 3.5 J/kgK and 150, 182, 176 J/kg for the investigated samples, respectively. The change in structural, magnetic, and magnetocaloric effect attributed to the superexchange mechanism of Ni2+–O–Mn3+ and Ni2+–O–Mn4+. The various atomic sizes of Eu, Gd, and Tb affect the ratio of Mn4+/Mn3+, which is responsible for the considerable change in properties of double perovskite.
Disturbance of phylogenetic layer-specific adaptation of human brain gene expression in Alzheimer's disease
Authors: Jorge Natasha Andressa Nogueira , Ueberham Uwe , Knobloch Mara , Stadler Peter F. , Fallmann Jörg , Arendt Thomas 
Published: October 2021

AbstractAlzheimer's disease (AD) is a progressive neurodegenerative disorder with typical neuropathological hallmarks, such as neuritic plaques and neurofibrillary tangles, preferentially found at layers III and V. The distribution of both hallmarks provides the basis for the staging of AD, following a hierarchical pattern throughout the cerebral cortex. To unravel the background of this layer-specific vulnerability, we evaluated differential gene expression ofsupragranularandinfragranular layersandsubcortical white matterin both healthy controls and AD patients. We identified AD-associated layer-specific differences involving protein-coding and non-coding sequences, most of those present in thesubcortical white matter, thus indicating a critical role for long axons and oligodendrocytes in AD pathomechanism. In addition, GO analysis identified networks containing synaptic vesicle transport, vesicle exocytosis and regulation of neurotransmitter levels. Numerous AD-associated layer-specifically expressed genes were previously reported to undergo layer-specific switches in recent hominid brain evolution between layers V and III, i.e., those layers that are most vulnerable to AD pathology. Against the background of our previous finding of accelerated evolution of AD-specific gene expression, here we suggest a critical role in AD pathomechanism for this phylogenetic layer-specific adaptation of gene expression, which is most prominently seen in the white matter compartment.
Changes in metabolic syndrome affect the health-related quality of life of community-dwelling adults
Authors: Lin Yi-Hsuan , Chang Hsiao-Ting , Tseng Yen-Han , Chen Harn-Shen , Chiang Shu-Chiung , Chen Tzeng-Ji , Hwang Shinn-Jang 
Published: October 2021

AbstractMetabolic syndrome (MetS) is associated with cardiovascular diseases, type 2 diabetes, chronic renal diseases, and all-cause mortality. Furthermore, MetS is associated with poor health-related quality of life (HRQOL). However, the impact of dynamic changes in MetS on changes in the HRQOL was not previously explored. This was an eight-year, prospective cohort study in which 906 middle-aged adults from Shipai, Taipei in northern Taiwan were enrolled during 2009–2010 (baseline). Of those sampled, 427 participants completed the follow-up investigation after 8 years. The HRQOL was measured using the Short Form Health Survey (SF-36). Other variables including age, sex, marital status, level of education, smoking, alcohol consumption, baseline body mass index, and changes in physical activity were adjusted. Compared with adults who never experienced MetS, adults with persistent MetS had a negative change in mental HRQOL (β − 4.20, 95% CI − 7.54 to − 0.86, p = 0.01). The negative changes of persistent MetS on the HRQOL were in the domains of vitality and mental health (β − 4.42, 95% CI − 8.10 to − 0.73 and β − 3.47, 95% CI − 6.90 to − 0.04, respectively). Women and overweight adults were vulnerable to the detrimental effects of persistent MetS. For better HRQOL, more resources should be devoted to reversing MetS in public health.
Molecular rationale for SARS-CoV-2 spike circulating mutations able to escape bamlanivimab and etesevimab monoclonal antibodies
Authors: Laurini Erik , Marson Domenico , Aulic Suzana , Fermeglia Alice , Pricl Sabrina 
Published: October 2021

AbstractThe purpose of this work is to provide an in silico molecular rationale of the role eventually played by currently circulating mutations in the receptor binding domain of the SARS-CoV-2 spike protein (S-RBDCoV‑2) in evading the immune surveillance effects elicited by the two Eli Lilly LY-CoV555/bamlanivimab and LY-CoV016/etesevimab monoclonal antibodies. The main findings from this study show that, compared to the wild-type SARS-CoV-2 spike protein, mutations E484A/G/K/Q/R/V, Q493K/L/R, S494A/P/R, L452R and F490S are predicted to be markedly resistant to neutralization by LY-CoV555, while mutations K417E/N/T, D420A/G/N, N460I/K/S/T, T415P, and Y489C/S are predicted to confer LY-CoV016 escaping advantage to the viral protein. A challenge of our global in silico results against relevant experimental data resulted in an overall 90% agreement. Thus, the results presented provide a molecular-based rationale for all relative experimental findings, constitute a fast and reliable tool for identifying and prioritizing all present and newly reported circulating spike SARS-CoV-2 variants with respect to antibody neutralization, and yield substantial structural information for the development of next-generation vaccines and monoclonal antibodies more resilient to viral evolution.
Evolution of MET and NRAS gene amplification as acquired resistance mechanisms in EGFR mutant NSCLC
Authors: Peters T. L. , Patil T. , Le A. T. , Davies K. D. , Brzeskiewicz P. M. , Nijmeh H. , Bao L. , Camidge D. R. , Aisner D. L. , Doebele R. C. 
Published: October 2021

AbstractEGFR mutant non-small cell lung cancer patients' disease demonstrates remarkable responses to EGFR-targeted therapy, but inevitably they succumb to acquired resistance, which can be complex and difficult to treat. Analyzing acquired resistance through broad molecular testing is crucial to understanding the resistance mechanisms and developing new treatment options. We performed diverse clinical testing on a patient with successive stages of acquired resistance, first to an EGFR inhibitor with MET gene amplification and then subsequently to a combination EGFR and MET targeted therapies. A patient-derived cell line obtained at the time of disease progression was used to identify NRAS gene amplification as an additional driver of drug resistance to combination EGFR/MET therapies. Analysis of downstream signaling revealed extracellular signal-related kinase activation that could only be eliminated by trametinib treatment, while Akt activation could be modulated by various combinations of MET, EGFR, and PI3K inhibitors. The combination of an EGFR inhibitor with a MEK inhibitor was identified as a possible treatment option to overcome drug resistance related to NRAS gene amplification.
Cross-field optoelectronic modulation via inter-coupled ferroelectricity in 2D In2Se3
Authors: Dutta Debopriya , Mukherjee Subhrajit , Uzhansky Michael , Koren Elad 
Published: October 2021

AbstractThe ability to couple the in-plane (IP) and out-of-plane (OOP) dipole polarizations in ferroelectric In2Se3 makes it a promising material for multimodal memory and optoelectronic applications. Herein, we experimentally demonstrate the cross-field optoelectronic modulation in In2Se3 based field-effect devices. Surface potential measurements of In2Se3 based devices directly reveal the bidirectional dipole locking following high gate voltage pulses. The experimental evidence of hysteretic change in the IP electrical field facilitating a nonvolatile memory switch, was further explored by performing photocurrent measurements. Fabricated photodetectors presented multilevel photocurrent characteristics showing promise for nonvolatile memory and electro-optical applications.