bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of diffusion-weighted and contrast-enhanced magnetic resonance imaging in diagnosing and differentiating between high- and low-grade uterine endometrial stromal sarcoma
Authors: Huang Yen-Ling , Ueng Shir-Hwa , Chen Kueian , Huang Yu-Ting , Lu Hsin-Ying , Ng Koon-Kwan , Chang Ting-Chang , Lai Chyong-Huey , Lin Gigin 
Published: September 2019

Abstract

Background
Endometrial stromal sarcoma (ESS) is a rare uterine malignancy that features different prognoses for its high- and low-grade subtypes. We investigated the diagnostic accuracy of magnetic resonance (MR) imaging in diagnosing and differentiating between high- and low-grade ESS.

Methods
We retrospectively reviewed the preoperative pelvic MR images of consecutive patients who received histologically confirmed diagnoses of high-grade ESS (n = 11) and low-grade ESS (n = 9) and T2-hyperintense leiomyoma (n = 16). Two radiologists independently evaluated imaging features in T1-, T2-, and diffusion-weighted and contrast-enhanced MR images. Statistical analysis included Mann-Whitney tests and Fisher’s exact test, with sensitivity, specificity and diagnostic accuracy of imaging features.

Results
High-grade ESS was associated with significantly more extensive necrosis and hemorrhage and distinct feather-like enhancement compared with low-grade ESS (P < .05 for all). The feather-like enhancement pattern yielded a diagnostic accuracy of 95%, sensitivity of 91%, and specificity of 100% in differentiating high-grade from low-grade ESS. This imaging characteristic was significantly superior to the necrosis (80%, P = .033) or hemorrhage (75%, P = .007). Both high- and low-grade ESS demonstrated T2 hypointense bands, marginal nodules, intratumoral nodules, and worm-like intra-myometrial nodules, and their tumor apparent diffusion coefficient (ADC) values were significantly lower than those of T2-hyperintense leiomyomas (P < .001).

Conclusions
Diffusion-weighted MR imaging is useful in diagnosing ESS against T2-hyperintense leiomyomas, and contrast enhancement aids in further differentiating between high- and low-grade ESS.
Bergmann’s rule and Allen’s rule in two passerine birds in China
Authors: Fan Liqing , Cai Tianlong , Xiong Ying , Song Gang , Lei Fumin 
Published: September 2019

AbstractBackgroundAnimals that live at higher latitudes/elevations would have a larger body size (Bergmann’s rule) and a smaller appendage size (Allen’s rule) for thermoregulatory reasons. According to the heat conservation hypothesis, large body size and small appendage size help animals retain heat in the cold, while small body size and large appendage size help them dissipate heat in the warm. For animals living in seasonal climates, the need for conserving heat in the winter may tradeoff with the need for dissipating heat in the summer. In this study, we tested Bergmann’s rule and Allen’s rule in two widely-distributed passerine birds, the Oriental Magpie (Pica serica) and the Oriental Tit (Parus minor), across geographic and climatic gradients in China.MethodsWe measured body size (body mass and wing length) and appendage size (bill length and tarsus length) of 165 Oriental Magpie and 410 Oriental Tit individuals collected from Chinese mainland. We used linear mixed-effect models to assess variation patterns of body size and appendage size along geographic and climatic gradients.ResultsOriental Magpies have a larger appendage size and Oriental Tits have a smaller body size in warmer environments. Appendage size in Oriental Magpies and body size in Oriental Tits of both sexes were more closely related to the climates in winter than in summer. Minimum temperature of coldest month is the most important factor related to bill length and tarsus length of male Oriental Magpies, and wing length of male and female Oriental Tits. Bill length and tarsus length in female Oriental Magpies were related to the annual mean temperature and mean temperature of coldest quarter, respectively.ConclusionsIn this study, Oriental Magpies and Oriental Tits followed Allen’s rule and Bergmann’ rule respectively. Temperatures in the winter, rather than temperatures in the summer, drove morphological measurements in Oriental Magpies and Oriental Tits in Chinese mainland, demonstrating that the morphological measurements reflect selection for heat conservation rather than for heat dissipation.
High-Fat Overfeeding Impairs Peripheral Glucose Metabolism and Muscle Microvascular eNOS Ser1177 Phosphorylation
Authors: Parry Siôn A , Turner Mark C , Woods Rachel M , James Lewis J , Ferguson Richard A , Cocks Matthew , Whytock Katie L , Strauss Juliette A , Shepherd Sam O , Wagenmakers Anton J M , van Hall Gerrit , Hulston Carl J 
Published: September 2019

Abstract

Context
The mechanisms responsible for dietary fat-induced insulin resistance of skeletal muscle and its microvasculature are only partially understood.

Objective
To determine the impact of high-fat overfeeding on postprandial glucose fluxes, muscle insulin signaling, and muscle microvascular endothelial nitric oxide synthase (eNOS) content and activation.

Design
Fifteen non-obese volunteers consumed a high-fat (64%) high-energy (+47%) diet for 7 days. Experiments were performed before and after the diet. Stable isotope tracers were used to determine glucose fluxes in response to carbohydrate plus protein ingestion. Muscle insulin signaling was determined as well as the content and activation state of muscle microvascular eNOS.

Results
High-fat overfeeding impaired postprandial glycemic control as demonstrated by higher concentrations of glucose (+11%; P = 0.004) and insulin (+19%; P = 0.035). Carbohydrate plus protein ingestion suppressed endogenous glucose production to a similar extent before and after the diet. Conversely, high-fat overfeeding reduced whole-body glucose clearance (–16%; P = 0.021) and peripheral insulin sensitivity (–26%; P = 0.006). This occurred despite only minor alterations in skeletal muscle insulin signaling. High-fat overfeeding reduced eNOS content in terminal arterioles (P = 0.017) and abolished the increase in eNOS Ser1177 phosphorylation that was seen after carbohydrate plus protein ingestion.

Conclusion
High-fat overfeeding impaired whole-body glycemic control due to reduced glucose clearance, not elevated endogenous glucose production. The finding that high-fat overfeeding abolished insulin-mediated eNOS Ser1177 phosphorylation in the terminal arterioles suggests that impairments in the vasodilatory capacity of the skeletal muscle microvasculature may contribute to early dietary fat-induced impairments in glycemic control.
Uterine Fluid Proteins for Minimally Invasive Assessment of Endometrial Receptivity
Authors: Kasvandik Sergo , Saarma Merilin , Kaart Tanel , Rooda Ilmatar , Velthut-Meikas Agne , Ehrenberg Aivar , Gemzell Kristina , Lalitkumar Parameswaran Grace , Salumets Andres , Peters Maire 
Published: September 2019

AbstractContextClinically used endometrial (EM) receptivity assays are based on transcriptomic patterning of biopsies at midsecretory endometrium (MSE) to identify the possible displacement or disruption of window of implantation (WOI) in patients with recurrent implantation failure (RIF). However, biopsies are invasive and cannot be performed in the same cycle with in vitro fertilization embryo transfer, while uterine fluid (UF) analysis is considered minimally invasive and can immediately precede embryo transfer.ObjectiveTo determine whether UF proteome can be used for WOI monitoring and whether it would highlight the etiology of RIF.PatientsPaired early secretory endometrial (ESE) and MSE UF samples from six fertile control women for discovery, and an additional 11 paired ESE/MSE samples from controls and 29 MSE samples from RIF patients for validation.ResultsUsing discovery mass spectrometry (MS) proteomics we detected 3158 proteins from secretory phase UF of which 367 undergo significant (q &lt; 0.05) proteomic changes while transitioning from ESE to MSE. Forty-five proteins were further validated with targeted MS, and 21 were found to display similar levels between control ESE and RIF MSE, indicating displacement of the WOI. A panel of PGR, NNMT, SLC26A2 and LCN2 demonstrated specificity and sensitivity of 91.7% for distinguishing MSE from ESE samples. The same panel distinguished control MSE samples from RIF MSE with a 91.7% specificity and 96.6% sensitivity.ConclusionUF proteins can be used for estimating uterine receptivity with minimal invasiveness. Women with RIF appear to have altered MSE UF profiles that may contribute to their low IVF success rate.
Inducible SMARCAL1 knockdown in iPSC reveals a link between replication stress and altered expression of master differentiation genes
Authors: Pugliese Giusj Monia , Salaris Federico , Palermo Valentina , Marabitti Veronica , Morina Nicolò , Rosa Alessandro , Franchitto Annapaola , Pichierri Pietro 
Published: September 2019

ABSTRACT
Schimke immuno-osseous dysplasia is an autosomal recessive genetic osteochondrodysplasia characterized by dysmorphism, spondyloepiphyseal dysplasia, nephrotic syndrome and frequently T cell immunodeficiency. Several hypotheses have been proposed to explain the pathophysiology of the disease; however, the mechanism by which SMARCAL1 mutations cause the syndrome is elusive. Here, we generated a conditional SMARCAL1 knockdown model in induced pluripotent stem cells (iPSCs) to mimic conditions associated with the severe form the disease. Using multiple cellular endpoints, we characterized this model for the presence of phenotypes linked to the replication caretaker role of SMARCAL1. Our data show that conditional knockdown of SMARCAL1 in human iPSCs induces replication-dependent and chronic accumulation of DNA damage triggering the DNA damage response. Furthermore, they indicate that accumulation of DNA damage and activation of the DNA damage response correlates with increased levels of R-loops and replication-transcription interference. Finally, we provide evidence that SMARCAL1-deficient iPSCs maintain active DNA damage response beyond differentiation, possibly contributing to the observed altered expression of a subset of germ layer-specific master genes. Confirming the relevance of SMARCAL1 loss for the observed phenotypes, they are prevented or rescued after re-expression of wild-type SMARCAL1 in our iPSC model. In conclusion, our conditional SMARCAL1 knockdown model in iPSCs may represent a powerful model when studying pathogenetic mechanisms of severe Schimke immuno-osseous dysplasia.
Chemically induced neurite-like outgrowth reveals a multicellular network function in patient-derived glioblastoma cells
Authors: da Silva Barbara , Irving Bronwyn K. , Polson Euan S. , Droop Alastair , Griffiths Hollie B. S. , Mathew Ryan K. , Stead Lucy F. , Marrison Joanne , Williams Courtney , Williams Jennifer , Short Susan C. , Scarcia Margherita , O'Toole Peter J. , Allison Simon J. , Mavria Georgia , Wurdak Heiko 
Published: September 2019

ABSTRACT
Tumor stem cells and malignant multicellular networks have been separately implicated in the therapeutic resistance of glioblastoma multiforme (GBM), the most aggressive type of brain cancer in adults. Here, we show that small-molecule inhibition of RHO-associated serine/threonine kinase proteins (ROCKi) significantly promoted the outgrowth of neurite-like cell projections in cultures of heterogeneous patient-derived GBM stem-like cells. These projections formed de novo-induced cellular network (iNet) ‘webs’, which regressed after withdrawal of ROCKi. Connected cells within the iNet web exhibited long range Ca2+ signal transmission, and significant lysosomal and mitochondrial trafficking. In contrast to their less-connected vehicle control counterparts, iNet cells remained viable and proliferative after high-dose radiation. These findings demonstrate a link between ROCKi-regulated cell projection dynamics and the formation of radiation-resistant multicellular networks. Our study identifies means to reversibly induce iNet webs ex vivo, and may thereby accelerate future studies into the biology of GBM cellular networks.
Perturbed mitochondria–ER contacts in live neurons that model the amyloid pathology of Alzheimer's disease
Authors: Martino Adami Pamela V. , Nichtová Zuzana , Weaver David B. , Bartok Adam , Wisniewski Thomas , Jones Drew R. , Do Carmo Sonia , Castaño Eduardo M. , Cuello A. Claudio , Hajnóczky György , Morelli Laura 
Published: September 2019

ABSTRACT
The use of fixed fibroblasts from familial and sporadic Alzheimer's disease patients has previously indicated an upregulation of mitochondria–ER contacts (MERCs) as a hallmark of Alzheimer's disease. Despite its potential significance, the relevance of these results is limited because they were not extended to live neurons. Here we performed a dynamic in vivo analysis of MERCs in hippocampal neurons from McGill-R-Thy1-APP transgenic rats, a model of Alzheimer's disease-like amyloid pathology. Live FRET imaging of neurons from transgenic rats revealed perturbed ‘lipid-MERCs’ (gap width &lt;10 nm), while ‘Ca2+-MERCs’ (10–20 nm gap width) were unchanged. In situ TEM showed no significant differences in the lipid-MERCs:total MERCs or lipid-MERCs:mitochondria ratios; however, the average length of lipid-MERCs was significantly decreased in neurons from transgenic rats as compared to controls. In accordance with FRET results, untargeted lipidomics showed significant decreases in levels of 12 lipids and bioenergetic analysis revealed respiratory dysfunction of mitochondria from transgenic rats. Thus, our results reveal changes in MERC structures coupled with impaired mitochondrial functions in Alzheimer's disease-related neurons.
This article has an associated First Person interview with the first author of the paper.
COMMD1 and PtdIns(4,5)P2 interaction maintain ATP7B copper transporter trafficking fidelity in HepG2 cells
Authors: Stewart Davis J. , Short Kristopher K. , Maniaci Breanna N. , Burkhead Jason L. 
Published: September 2019

ABSTRACT
Copper-responsive intracellular ATP7B trafficking is crucial for maintaining the copper balance in mammalian hepatocytes and thus copper levels in organs. The copper metabolism domain-containing protein 1 (COMMD1) binds both the ATP7B copper transporter and phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2], whereas COMMD1 loss causes hepatocyte copper accumulation. Although it is clear that COMMD1 is localized to endocytic trafficking complexes, a direct function for COMMD1 in ATP7B trafficking has not yet been defined. In this study, experiments using quantitative colocalization analysis reveal that COMMD1 modulates copper-responsive ATP7B trafficking through recruitment to PtdIns(4,5)P2. Decreased COMMD1 abundance results in loss of ATP7B from lysosomes and the trans-Golgi network (TGN) in high copper conditions, although excess expression of COMMD1 also disrupts ATP7B trafficking and TGN structure. Overexpression of COMMD1 mutated to inhibit PtdIns(4,5)P2 binding has little impact on ATP7B trafficking. A mechanistic PtdIns(4,5)P2-mediated function for COMMD1 is proposed that is consistent with decreased cellular copper export as a result of disruption of the ATP7B trafficking itinerary and early endosome accumulation when COMMD1 is depleted. PtdIns(4,5)P2 interaction with COMMD1 as well as COMMD1 abundance could both be important in maintenance of specific membrane protein trafficking pathways.
Annexin A5 regulates surface αvβ5 integrin for retinal clearance phagocytosis
Authors: Yu Chen , Muñoz Luis E. , Mallavarapu Mallika , Herrmann Martin , Finnemann Silvia C. 
Published: September 2019

ABSTRACT
Diurnal clearance phagocytosis by the retinal pigment epithelium (RPE) is a conserved efferocytosis process whose binding step is mediated by αvβ5 integrin receptors. Two related annexins, A5 (ANXA5) and A6 (ANXA6), share an αvβ5 integrin-binding motif. Here, we report that ANXA5, but not ANXA6, regulates the binding capacity for spent photoreceptor outer segment fragments or apoptotic cells by fibroblasts and RPE. Similar to αvβ5-deficient RPE, ANXA5−/− RPE in vivo lacks the diurnal burst of phagocytosis that follows photoreceptor shedding in wild-type retina. Increasing ANXA5 in cells lacking αvβ5 or increasing αvβ5 in cells lacking ANXA5 does not affect particle binding. Association of cytosolic ANXA5 and αvβ5 integrin in RPE in culture and in vivo further supports their functional interdependence. Silencing ANXA5 is sufficient to reduce levels of αvβ5 receptors at the apical phagocytic surface of RPE cells. The effect of ANXA5 on surface αvβ5 and on particle binding requires the C-terminal ANXA5 annexin repeat but not its unique N-terminus. These results identify a novel role for ANXA5 specifically in the recognition and binding step of clearance phagocytosis, which is essential to retinal physiology.
This article has an associated First Person interview with the first author of the paper.
Yank: the time derivative of force is an important biomechanical variable in sensorimotor systems
Authors: Lin David C. , McGowan Craig P. , Blum Kyle P. , Ting Lena H. 
Published: September 2019

ABSTRACT
The derivative of force with respect to time does not have a standard term in physics. As a consequence, the quantity has been given a variety of names, the most closely related being ‘rate of force development’. The lack of a proper name has made it difficult to understand how different structures and processes within the sensorimotor system respond to and shape the dynamics of force generation, which is critical for survival in many species. We advocate that ∂/∂t be termed ‘yank’, a term that has previously been informally used and never formally defined. Our aim in this Commentary is to establish the significance of yank in how biological motor systems are organized, evolve and adapt. Further, by defining the quantity in mathematical terms, several measurement variables that are commonly reported can be clarified and unified. In this Commentary, we first detail the many types of motor function that are affected by the magnitude of yank generation, especially those related to time-constrained activities. These activities include escape, prey capture and postural responses to perturbations. Next, we describe the multi-scale structures and processes of the musculoskeletal system that influence yank and can be modified to increase yank generation. Lastly, we highlight recent studies showing that yank is represented in the sensory feedback system, and discuss how this information is used to enhance postural stability and facilitate recovery from postural perturbations. Overall, we promote an increased consideration of yank in studying biological motor and sensory systems.
Self-Propelled Autonomous Mg/Pt Janus Micromotor Interaction with Human Cells
Authors: Kong Lei , Rosli Nur Farhanah , Chia Hui Ling , Guan Jianguo , Pumera Martin 
Published: September 2019

Abstract
Magnesium (Mg)-based micromotors have attracted considerable attention as they are capable of moving in water and human blood plasma without external fuels. It has also been demonstrated that they have potential for drug delivery in mouse stomach. However, their biocompatibility and cytotoxicity to human cells have yet to be studied. Therefore, we performed cytotoxicity study of Mg/Pt Janus micromotors with human lung carcinoma epithelial cells (A549), human breast cancer cells (MCF-7), human embryonic kidney cells (HEK-293), human liver carcinoma cells (HepG2) and human cervical cancer cells (HeLa). The highest concentration of micromotors tested, 200 µg mL−1, drastically induced a high toxic effect on the cells and reduced the cell viability to below 60%. This shows while Pt/Au nanomachines were found to be safe previously, this is not the case of the Mg/Pt micromachines.
Screening is not associated with reduced incidence of gonorrhoea or chlamydia in men who have sex with men (MSM); an ecological study of 23 European countries
Authors: Kenyon Chris 
Published: September 2019

Background: Increasing rates of antimicrobial resistance has motivated a reassessment of if intensive screening for gonorrhoea and chlamydia is associated with a reduction in the prevalence of these infections in men who have sex with men (MSM). Methods: Spearman’s correlation was used to evaluate the country-level correlation between the intensity of self-reported sexual transmitted infection (STI) screening in MSM (both anal and urethral screening, taken from a large internet survey of MSM) and the incidence (taken from ECDC surveillance figures) and prevalence (taken from a literature review of studies estimating prevalence in MSM attending STI clinics) of gonorrhoea and chlamydia. Results: The intensity of both anal and genital screening was found to be positively associated with country level gonorrhoea incidence rates (rho 0.74; p=0.0004; rho=0.73; p=0.0004, respectively) and Ct incidence rates (rho 0.71; p=0.001; rho=0.78; p=0.0001, respectively). No associations were found between anal or genital screening intensity and Ng prevalence in clinic populations (Table 2). Conclusions: We found no evidence of a negative association between screening intensity and the prevalence of gonorrhoea or chlamydia in MSM. Randomized controlled trials are urgently required to evaluate if the high antimicrobial exposure resulting from intensive screening programmes is justified.
Can Reputation Discipline the Gig Economy? Experimental Evidence from an Online Labor Market
Authors: Benson Alan , Sojourner Aaron , Umyarov Akhmed 
Published: September 2019

Just as employers face uncertainty when hiring workers, workers also face uncertainty when accepting employment, and bad employers may opportunistically depart from expectations, norms, and laws. However, prior research in economics and information sciences has focused sharply on the employer’s problem of identifying good workers rather than vice versa. This issue is especially pronounced in markets for gig work, including online labor markets, in which platforms are developing strategies to help workers identify good employers. We build a theoretical model for the value of such reputation systems and test its predictions on Amazon Mechanical Turk, on which employers may decline to pay workers while keeping their work product and workers protect themselves using third-party reputation systems, such as Turkopticon. We find that (1) in an experiment on worker arrival, a good reputation allows employers to operate more quickly and on a larger scale without loss to quality; (2) in an experimental audit of employers, working for good-reputation employers pays 40% higher effective wages because of faster completion times and lower likelihoods of rejection; and (3) exploiting reputation system crashes, the reputation system is particularly important to small, good-reputation employers, which rely on the reputation system to compete for workers against more established employers. This is the first clean field evidence of the effects of employer reputation in any labor market and is suggestive of the special role that reputation-diffusing technologies can play in promoting gig work, in which conventional labor and contract laws are weak. This paper was accepted by Chris Forman, information science.