bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smoking accelerates renal cystic disease and worsens cardiac phenotype in Pkd1-deficient mice
Authors: Sousa Marciana V. , Amaral Andressa G. , Freitas Jessica A. , Murata Gilson M. , Watanabe Elieser H. , Balbo Bruno E. , Tavares Marcelo D. , Hortegal Renato A. , Rocon Camila , Souza Leandro E. , Irigoyen Maria C. , Salemi Vera M. , Onuchic Luiz F. 
Published: July 2021

AbstractSmoking has been associated with renal disease progression in ADPKD but the underlying deleterious mechanisms and whether it specifically worsens the cardiac phenotype remain unknown. To investigate these matters, Pkd1-deficient cystic mice and noncystic littermates were exposed to smoking from conception to 18 weeks of age and, along with nonexposed controls, were analyzed at 13–18 weeks. Renal cystic index and cyst-lining cell proliferation were higher in cystic mice exposed to smoking than nonexposed cystic animals. Smoking increased serum urea nitrogen in cystic and noncystic mice and independently enhanced tubular cell proliferation and apoptosis. Smoking also increased renal fibrosis, however this effect was much higher in cystic than in noncystic animals. Pkd1 deficiency and smoking showed independent and additive effects on reducing renal levels of glutathione. Systolic function and several cardiac structural parameters were also negatively affected by smoking and the Pkd1-deficient status, following independent and additive patterns. Smoking did not increase, however, cardiac apoptosis or fibrosis in cystic and noncystic mice. Notably, smoking promoted a much higher reduction in body weight in Pkd1-deficient than in noncystic animals. Our findings show that smoking aggravated the renal and cardiac phenotypes of Pkd1-deficient cystic mice, suggesting that similar effects may occur in human ADPKD.
Maximal modularity and the optimal size of parliaments
Authors: Gamberi Luca , Förster Yanik-Pascal , Tzanis Evan , Annibale Alessia , Vivo Pierpaolo 
Published: July 2021

AbstractAn important question in representative democracies is how to determine the optimal parliament size of a given country. According to an old conjecture, known as the cubic root law, there is a fairly universal power-law relation, with an exponent equal to 1/3, between the size of an elected parliament and the country’s population. Empirical data in modern European countries support such universality but are consistent with a larger exponent. In this work, we analyse this intriguing regularity using tools from complex networks theory. We model the population of a democratic country as a random network, drawn from a growth model, where each node is assigned a constituency membership sampled from an available set of size D. We calculate analytically the modularity of the population and find that its functional relation with the number of constituencies is strongly non-monotonic, exhibiting a maximum that depends on the population size. The criterion of maximal modularity allows us to predict that the number of representatives should scale as a power-law in the size of the population, a finding that is qualitatively confirmed by the empirical analysis of real-world data.
Enhanced cellular engraftment of adipose-derived mesenchymal stem cell spheroids by using nanosheets as scaffolds
Authors: Nagano Hisato , Suematsu Yoshitaka , Takuma Megumi , Aoki Shimpo , Satoh Ayano , Takayama Eiji , Kinoshita Manabu , Morimoto Yuji , Takeoka Shinji , Fujie Toshinori , Kiyosawa Tomoharu 
Published: July 2021

AbstractThe short survival time of transplanted adipose-derived mesenchymal stem cells (ASCs) is a problem for skin wound healing. Transplantation after the formation of cellular spheroids has been investigated as a promising method for prolonging cellular survival. However, there have been technical restrictions for transplantation of spheroids in clinical practice. Here, we show an effective method for transplantation of ASC spheroids onto skin wounds in order to efficiently cure refractory ulcers. To assist anchoring of spheroids onto skin wounds, we used a 120-nm-thick free-standing film (nanosheet) that has a highly adhesive property. Bioluminescence imaging showed that ASC spheroids carried by the nanosheet survived for 14 days, which is about two-times longer than that previously reported. Wounds treated with a nanosheet carrying ASC spheroids were 4-times smaller than untreated wounds on day 14. This method for transplantation of spheroids could be applied to cell therapy for various refractory skin wounds.
A system biology approach based on metabolic biomarkers and protein–protein interactions for identifying pathways underlying schizophrenia and bipolar disorder
Authors: Altaf-Ul-Amin Md. , Hirose Kazuhisa , Nani João V. , Porta Lucas C. , Tasic Ljubica , Hossain Shaikh Farhad , Huang Ming , Ono Naoaki , Hayashi Mirian A. F. , Kanaya Shigehiko 
Published: July 2021

AbstractMental disorders (MDs), including schizophrenia (SCZ) and bipolar disorder (BD), have attracted special attention from scientists due to their high prevalence and significantly debilitating clinical features. The diagnosis of MDs is still essentially based on clinical interviews, and intensive efforts to introduce biochemical based diagnostic methods have faced several difficulties for implementation in clinics, due to the complexity and still limited knowledge in MDs. In this context, aiming for improving the knowledge in etiology and pathophysiology, many authors have reported several alterations in metabolites in MDs and other brain diseases. After potentially fishing all metabolite biomarkers reported up to now for SCZ and BD, we investigated here the proteins related to these metabolites in order to construct a protein–protein interaction (PPI) network associated with these diseases. We determined the statistically significant clusters in this PPI network and, based on these clusters, we identified 28 significant pathways for SCZ and BDs that essentially compose three groups representing three major systems, namely stress response, energy and neuron systems. By characterizing new pathways with potential to innovate the diagnosis and treatment of psychiatric diseases, the present data may also contribute to the proposal of new intervention for the treatment of still unmet aspects in MDs.
Differences in heart rate variability and body composition in breast cancer survivors and women without cancer
Authors: Escutia-Reyes Daniel , de Jesús Garduño-García José , Emilio-López-Chávez Gerardo , Gómez-Villanueva Ángel , Pliego-Carrillo Adriana Cristina , Soto-Piña Alexandra Estela , Reyes-Lagos José Javier 
Published: July 2021

AbstractThe aim of this study was to explore cardiac autonomic changes assessed by linear and nonlinear indexes of heart rate variability (HRV) and body composition modifications in breast cancer survivors and cancer-free control women. Women who were breast cancer survivors (BCS, n = 27) and without cancer with similar characteristics (Control, n = 31) were recruited for this study. We calculated some relevant linear and nonlinear parameters of 5 min of RR interval time series such as mean RR interval (RRave), the corrected Poincaré index (cSD1/SD2), the sample entropy (SampEn), the long-term fractal scaling exponent (α2) and 2UV from symbolic dynamics. Additionally, we indirectly assessed body composition measures such as body weight, fat mass, visceral fat rating (VFR), normalized VRF (nVFR), muscle mass, metabolic age, and total body water. We found that diverse HRV indexes and only one body composition measure showed statistical differences (p < 0.05) between the BCS and Control groups. RRave: 729 (648–802) vs. 795 (713–852) ms; cSD2/SD1: 3.4 (2.7–5.0) vs. 2.9 (2.3–3.5); SampEn: 1.5 (1.3–1.8) vs. 1.7 (1.5–1.8); α2: 0.6 (0.3–0.6) vs. 0.5 (0.4–0.5); 2UV: 7.1 (4.3–11.5) vs. 10.8 (6.4–15.7) and nVFR 0.12 (0.11–0.13) vs. 0.10 (0.08–0.12) points/kg, respectively. The nVFR was strongly significantly correlated with several indexes of HRV only in the BCS group.Our findings suggest that BCS exhibit lower parasympathetic cardiac activity and changes in HRV patterns compared to Controls. A concomitant increase of visceral fat, among other factors, may contribute to cardiac autonomic disturbances and changes in HRV patterns in BCS.
Reinforcement learning control of a biomechanical model of the upper extremity
Authors: Fischer Florian , Bachinski Miroslav , Klar Markus , Fleig Arthur , Müller Jörg 
Published: July 2021

AbstractAmong the infinite number of possible movements that can be produced, humans are commonly assumed to choose those that optimize criteria such as minimizing movement time, subject to certain movement constraints like signal-dependent and constant motor noise. While so far these assumptions have only been evaluated for simplified point-mass or planar models, we address the question of whether they can predict reaching movements in a full skeletal model of the human upper extremity. We learn a control policy using a motor babbling approach as implemented in reinforcement learning, using aimed movements of the tip of the right index finger towards randomly placed 3D targets of varying size. We use a state-of-the-art biomechanical model, which includes seven actuated degrees of freedom. To deal with the curse of dimensionality, we use a simplified second-order muscle model, acting at each degree of freedom instead of individual muscles. The results confirm that the assumptions of signal-dependent and constant motor noise, together with the objective of movement time minimization, are sufficient for a state-of-the-art skeletal model of the human upper extremity to reproduce complex phenomena of human movement, in particular Fitts’ Law and the$$\frac{2}{3}$$23Power Law. This result supports the notion that control of the complex human biomechanical system can plausibly be determined by a set of simple assumptions and can easily be learned.
A proposal for a new morphological classification of the popliteus muscle tendon with potential clinical and biomechanical significance
Authors: Olewnik Łukasz , LaPrade Robert F. , Paulsen Friedrich , Gonera Bartosz , Kurtys Konrad , Podgórski Michał , Aragonés Paloma , Sanudo J. Ramón , Polguj Michał 
Published: July 2021

AbstractThe purpose of this study was to characterize the morphological variations in the proximal attachments and create an accurate classification of the PPM for use in planning surgical procedures in this area, for evaluating radiological imaging and rehabilitation. One hundred and thirty-four lower limbs of body donors (52 woman and 82 man) fixed in 10% formalin solution were examined. The popliteus muscle was present in all 134 limbs. Four main types were identified with subtypes. The most common type was Type I (34.3%), characterized by a single tendon in the popliteus sulcus. Type II (30.6%) characterized by a main tendon in the popliteus sulcus and accessory bands. This type was divided into five subtypes (A–E) based on presence of specific accessory bands. Type III (15.3%) was characterized by two tendons in the popliteal sulcus. Type IV (19.4%) was characterized by two tendons in the popliteus sulcus and additional bands. This type was also divided into five subtypes (A–E) based on presence of specific accessory bands. The popliteofibular ligament was present in 90.3% of cases. A new classification based on a proximal attachment is proposed. The popliteus tendon is characterized by a very high morphological variability, which can affect posterolateral knee stability and the natural rotation of the tibia. Such a classification system may be useful for clinicians performing medical procedures within the knee joint, including orthopedic surgeons.
Automatic segmentation of uterine endometrial cancer on multi-sequence MRI using a convolutional neural network
Authors: Kurata Yasuhisa , Nishio Mizuho , Moribata Yusaku , Kido Aki , Himoto Yuki , Otani Satoshi , Fujimoto Koji , Yakami Masahiro , Minamiguchi Sachiko , Mandai Masaki , Nakamoto Yuji 
Published: July 2021

AbstractEndometrial cancer (EC) is the most common gynecological tumor in developed countries, and preoperative risk stratification is essential for personalized medicine. There have been several radiomics studies for noninvasive risk stratification of EC using MRI. Although tumor segmentation is usually necessary for these studies, manual segmentation is not only labor-intensive but may also be subjective. Therefore, our study aimed to perform the automatic segmentation of EC on MRI with a convolutional neural network. The effect of the input image sequence and batch size on the segmentation performance was also investigated. Of 200 patients with EC, 180 patients were used for training the modified U-net model; 20 patients for testing the segmentation performance and the robustness of automatically extracted radiomics features. Using multi-sequence images and larger batch size was effective for improving segmentation accuracy. The mean Dice similarity coefficient, sensitivity, and positive predictive value of our model for the test set were 0.806, 0.816, and 0.834, respectively. The robustness of automatically extracted first-order and shape-based features was high (median ICC = 0.86 and 0.96, respectively). Other high-order features presented moderate-high robustness (median ICC = 0.57–0.93). Our model could automatically segment EC on MRI and extract radiomics features with high reliability.
MYCN-induced nucleolar stress drives an early senescence-like transcriptional program in hTERT-immortalized RPE cells
Authors: Zanotti Sofia , Vanhauwaert Suzanne , Van Neste Christophe , Olexiouk Volodimir , Van Laere Jolien , Verschuuren Marlies , Van der Meulen Joni , Mus Liselot M. , Durinck Kaat , Tilleman Laurentijn , Deforce Dieter , Van Nieuwerburgh Filip , Hogarty Michael D. , Decaesteker Bieke , De Vos Winnok H. , Speleman Frank 
Published: July 2021

AbstractMYCN is an oncogenic driver in neural crest-derived neuroblastoma and medulloblastoma. To better understand the early effects of MYCN activation in a neural-crest lineage context, we profiled the transcriptome of immortalized human retina pigment epithelial cells with inducible MYCN activation. Gene signatures associated with elevated MYC/MYCN activity were induced after 24 h of MYCN activation, which attenuated but sustained at later time points. Unexpectedly, MYCN activation was accompanied by reduced cell growth. Gene set enrichment analysis revealed a senescence-like signature with strong induction of p53 and p21 but in the absence of canonical hallmarks of senescence such as β-galactosidase positivity, suggesting incomplete cell fate commitment. When scrutinizing the putative drivers of this growth attenuation, differential gene expression analysis identified several regulators of nucleolar stress. This process was also reflected by phenotypic correlates such as cytoplasmic granule accrual and nucleolar coalescence. Hence, we propose that the induction of MYCN congests the translational machinery, causing nucleolar stress and driving cells into a transient pre-senescent state. Our findings shed new light on the early events induced by MYCN activation and may help unravelling which factors are required for cells to tolerate unscheduled MYCN overexpression during early malignant transformation.
Climate and sea surface trends in the Galapagos Islands
Authors: Paltán Homero A. , Benitez Fátima L. , Rosero Paulina , Escobar-Camacho Daniel , Cuesta Francisco , Mena Carlos F. 
Published: July 2021

AbstractThe Galapagos Islands are a global hotspot of environmental change. However, despite their potentially major repercussions, little is known about current and expected changes in regional terrestrial climate variables and sea surface temperatures (SST). Here, by analysing existing meteorological observations and secondary datasets, we find that the Islands have warmed by about 0.6 °C since the early 1980s, while at the same time becoming drier. In fact, the onset of the wet season is currently delayed 20 days. This drying trend may reverse, however, given that future climate projections for the region suggest mean annual precipitation may increase between 20 and 70%. This would also be accompanied by more extreme wet and hot conditions. Further, we find that regional SST has increased by 1.2 °C over the last two decades. These changes will, in turn, translate into deterioration of marine ecosystems and coral, proliferation of invasive species, and damages to human water, food, and infrastructure systems. Future projections, however, may be overestimated due to the poor capacity of climatic models to capture Eastern-Pacific ENSO dynamics. Our findings emphasize the need to design resilient climate adaptation policies that will remain robust in the face of a wide range of uncertain and changing climatic futures.
Anthelmintic resistance and homeostatic plasticity (Brugia malayi)
Authors: Kashyap Sudhanva S. , Verma Saurabh , McHugh Mark , Wolday Mengisteab , Williams Paul D. , Robertson Alan P. , Martin Richard J. 
Published: July 2021

AbstractHomeostatic plasticity refers to the capacity of excitable cells to regulate their activity to make compensatory adjustments to long-lasting stimulation. It is found across the spectrum of vertebrate and invertebrate species and is driven by changes in cytosolic calcium; it has not been explored in parasitic nematodes when treated with therapeutic drugs. Here we have studied the adaptation of Brugia malayi to exposure to the anthelmintic, levamisole that activates muscle AChR ion-channels. We found three phases of the Brugia malayi motility responses as they adapted to levamisole: an initial spastic paralysis; a flaccid paralysis that follows; and finally, a recovery of motility with loss of sensitivity to levamisole at 4 h. Motility, calcium-imaging, patch-clamp and molecular experiments showed the muscle AChRs are dynamic with mechanisms that adjust their subtype composition and sensitivity to levamisole. This homeostatic plasticity allows the parasite to adapt resisting the anthelmintic.
TCERG1L allelic variation is associated with cisplatin-induced hearing loss in childhood cancer, a PanCareLIFE study
Authors: Meijer A. J. M. , Diepstraten F. A. , Langer T. , Broer L. , Domingo I. K. , Clemens E. , Uitterlinden A. G. , de Vries A. C. H. , van Grotel M. , Vermeij W. P. , Ozinga R. A. , Binder H. , Byrne J. , van Dulmen-den Broeder E. , Garrè M. L. , Grabow D. , Kaatsch P. , Kaiser M. , Kenborg L. , Winther J. F. , Rechnitzer C. , Hasle H. , Kepak T. , Kepakova K. , Tissing W. J. E. , van der Kooi A. L. F. , Kremer L. C. M. , Kruseova J. , Pluijm S. M. F. , Kuehni C. E. , van der Pal H. J. H. , Parfitt R. , Spix C. , Tillmanns A. , Deuster D. , Matulat P. , Calaminus G. , Hoetink A. E. , Elsner S. , Gebauer J. , Haupt R. , Lackner H. , Blattmann C. , Neggers S. J. C. M. M. , Rassekh S. R. , Wright G. E. B. , Brooks B. , Nagtegaal A. P. , Drögemöller B. I. , Ross C. J. D. , Bhavsar A. P. , am Zehnhoff-Dinnesen A. G. , Carleton B. C. , Zolk O. , van den Heuvel-Eibrink M. M. ,   the PanCareLIFE Consortium, de Vries A. C. H. , van Grotel M. , van Dulmen-den Broeder E. , van der Kooi A. L. F. , Kremer L. C. M. , van der Pal H. J. H. , Calaminus G. , Hoetink A. E. , van den Heuvel-Eibrink M. M. ,   and the CPNDS Consortium
Published: July 2021

AbstractIn children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10−10, OR 3.11, 95% CI 2.2–4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity.
Clinical subphenotypes in COVID-19: derivation, validation, prediction, temporal patterns, and interaction with social determinants of health
Authors: Su Chang , Zhang Yongkang , Flory James H. , Weiner Mark G. , Kaushal Rainu , Schenck Edward J. , Wang Fei 
Published: July 2021

AbstractThe coronavirus disease 2019 (COVID-19) is heterogeneous and our understanding of the biological mechanisms of host response to the viral infection remains limited. Identification of meaningful clinical subphenotypes may benefit pathophysiological study, clinical practice, and clinical trials. Here, our aim was to derive and validate COVID-19 subphenotypes using machine learning and routinely collected clinical data, assess temporal patterns of these subphenotypes during the pandemic course, and examine their interaction with social determinants of health (SDoH). We retrospectively analyzed 14418 COVID-19 patients in five major medical centers in New York City (NYC), between March 1 and June 12, 2020. Using clustering analysis, 4 biologically distinct subphenotypes were derived in the development cohort (N = 8199). Importantly, the identified subphenotypes were highly predictive of clinical outcomes (especially 60-day mortality). Sensitivity analyses in the development cohort, and rederivation and prediction in the internal (N = 3519) and external (N = 3519) validation cohorts confirmed the reproducibility and usability of the subphenotypes. Further analyses showed varying subphenotype prevalence across the peak of the outbreak in NYC. We also found that SDoH specifically influenced mortality outcome in Subphenotype IV, which is associated with older age, worse clinical manifestation, and high comorbidity burden. Our findings may lead to a better understanding of how COVID-19 causes disease in different populations and potentially benefit clinical trial development. The temporal patterns and SDoH implications of the subphenotypes may add insights to health policy to reduce social disparity in the pandemic.
MoC/MAPbI3 hybrid composites for efficient photocatalytic hydrogen evolution
Authors: Zhang Tiantian , Yu Jianfei , Huang Jiyao , Lan Shengnan , Lou Yongbing , Chen Jinxi 
Published: July 2021

A facile method was developed to fabricate MoC/MAPbI3 composites, which exhibit significantly improved hydrogen evolution activity and stability. The construction of MoC/MAPbI3 composites inhibits the recombination of carriers and holes.
First-principles insights into ammonia decomposition on the MoN(0001) surface
Authors: Yuan Kun , Hao Pengju , Li Xiaolin , Zhou Yang , Zhang Jianbo , Zhong Shengwen 
Published: July 2021

After NH3 adsorbed on the surface of MoN, one H atom was firstly removed to form NH2, and two adjacent NH2 molecules would combine to form N2H4 molecules, which leads to the step by step decomposition into N2.