bluuebunny/crossref_metadata_2025_split huggingface dataset:
Muscle length and joint angle influence spinal but not corticospinal excitability to the biceps brachii across forearm postures
Authors: Forman Davis A. , Abdel-Malek Daniel , Bunce Christopher M. F. , Holmes Michael W. R. 
Published: May 2019

Forearm rotation (supination/pronation) alters corticospinal excitability to the biceps brachii, but it is unclear whether corticospinal excitability is influenced by joint angle, muscle length, or both. Thus the purpose of this study was to separately examine elbow joint angle and muscle length on corticospinal excitability. Corticospinal excitability to the biceps and triceps brachii was measured using motor evoked potentials (MEPs) elicited via transcranial magnetic stimulation. Spinal excitability was measured using cervicomedullary motor evoked potentials (CMEPs) elicited via transmastoid electrical stimulation. Elbow angles were manipulated with a fixed biceps brachii muscle length (and vice versa) across five unique postures: 1) forearm neutral, elbow flexion 90°; 2) forearm supinated, elbow flexion 90°; 3) forearm pronated, elbow flexion 90°; 4) forearm supinated, elbow flexion 78°; and 5) forearm pronated, elbow flexion 113°. A musculoskeletal model determined biceps brachii muscle length for postures 1–3, and elbow joint angles ( postures 4–5) were selected to maintain biceps length across forearm orientations. MEPs and CMEPs were elicited at rest and during an isometric contraction of 10% of maximal biceps muscle activity. At rest, MEP amplitudes to the biceps were largest during supination, which was independent of elbow joint angle. CMEP amplitudes were not different when the elbow was fixed at 90° but were largest in pronation when muscle length was controlled. During an isometric contraction, there were no significant differences across forearm postures for either MEP or CMEP amplitudes. These results highlight that elbow joint angle and biceps brachii muscle length can each independently influence spinal excitability. NEW & NOTEWORTHY Changes in upper limb posture can influence the responsiveness of the central nervous system to artificial stimulations. We established a novel approach integrating neurophysiology techniques with biomechanical modeling. Through this approach, the effects of elbow joint angle and biceps brachii muscle length on corticospinal and spinal excitability were assessed. We demonstrate that spinal excitability is uniquely influenced by joint angle and muscle length, and this highlights the importance of accounting for muscle length in neurophysiological studies.
Toward Personalized Computer Simulation of Breast Cancer Treatment: A Multiscale Pharmacokinetic and Pharmacodynamic Model Informed by Multitype Patient Data
Authors: Lai Xiaoran , Geier Oliver M. , Fleischer Thomas , Garred Øystein , Borgen Elin , Funke Simon W. , Kumar Surendra , Rognes Marie E. , Seierstad Therese , Børresen-Dale Anne-Lise , Kristensen Vessela N. , Engebraaten Olav , Köhn-Luque Alvaro , Frigessi Arnoldo 
Published: May 2019

Abstract

The usefulness of mechanistic models to disentangle complex multiscale cancer processes, such as treatment response, has been widely acknowledged. However, a major barrier for multiscale models to predict treatment outcomes in individual patients lies in their initialization and parametrization, which needs to reflect individual cancer characteristics accurately. In this study, we use multitype measurements acquired routinely on a single breast tumor, including histopathology, MRI, and molecular profiling, to personalize parts of a complex multiscale model of breast cancer treated with chemotherapeutic and antiangiogenic agents. The model accounts for drug pharmacokinetics and pharmacodynamics. We developed an open-source computer program that simulates cross-sections of tumors under 12-week therapy regimens and used it to individually reproduce and elucidate treatment outcomes of 4 patients. Two of the tumors did not respond to therapy, and model simulations were used to suggest alternative regimens with improved outcomes dependent on the tumor's individual characteristics. It was determined that more frequent and lower doses of chemotherapy reduce tumor burden in a low proliferative tumor while lower doses of antiangiogenic agents improve drug penetration in a poorly perfused tumor. Furthermore, using this model, we were able to correctly predict the outcome in another patient after 12 weeks of treatment. In summary, our model bridges multitype clinical data to shed light on individual treatment outcomes.

Significance:
Mathematical modeling is used to validate possible mechanisms of tumor growth, resistance, and treatment outcome.
Chemotherapy-Induced Extracellular Vesicle miRNAs Promote Breast Cancer Stemness by Targeting ONECUT2
Authors: Shen Meng , Dong Chuan , Ruan Xianhui , Yan Wei , Cao Minghui , Pizzo Donald , Wu Xiwei , Yang Lin , Liu Liang , Ren Xiubao , Wang Shizhen Emily 
Published: May 2019

Abstract

Cancer-secreted, extracellular vesicle (EV)–encapsulated miRNAs enable cancer cells to communicate with each other and with noncancerous cells in tumor pathogenesis and response to therapies. Here, we show that treatment with a sublethal dose of chemotherapeutic agents induces breast cancer cells to secrete EV with the capacity to stimulate a cancer stem-like cell (CSC) phenotype, rendering cancer cells resistance to therapy. Chemotherapy induced breast cancer cells to secrete multiple EV miRNAs, including miR-9-5p, miR-195-5p, and miR-203a-3p, which simultaneously targeted the transcription factor One Cut Homeobox 2 (ONECUT2), leading to induction of CSC traits and expression of stemness-associated genes, including NOTCH1, SOX9, NANOG, OCT4, and SOX2. Inhibition of these miRNAs or restoration of ONECUT2 expression abolished the CSC-stimulating effect of EV from chemotherapy-treated cancer cells. In mice bearing xenograft mammary tumors, docetaxel treatment caused elevations of miR-9-5p, miR-195-5p, and miR-203a-3p in circulating EV and decreased ONECUT2 expression and increased levels of stemness-associated genes. These effects following chemotherapy were diminished in tumors deficient in exosome secretion. In human breast tumors, neoadjuvant chemotherapy decreased ONECUT2 expression in tumor cells. Our results indicate a mechanism by which cancer cells communicate with each other and self-adapt to survive in response to cytotoxic treatment. Targeting these adaptation mechanisms along with chemotherapy, such as by blocking the EV miRNA–ONECUT2 axis, represents a potential strategy to maximize the anticancer effect of chemotherapy and to reduce chemoresistance in cancer management.

Significance:
These findings reveal a critical mechanism of resistance to chemotherapy by which breast cancer cells secrete miRNA-containing extracellular vesicles to stimulate cancer stem cell-like features.
Smartwatch Performance for the Detection and Quantification of Atrial Fibrillation
Authors: Wasserlauf Jeremiah , You Cindy , Patel Ruchi , Valys Alexander , Albert David , Passman Rod 
Published: May 2019

Background:
Atrial fibrillation (AF) burden and duration appear to be related to stroke risk. A wearable consumer electronic device could provide long-term assessment of these measures inexpensively and noninvasively. This study compares the accuracy of an AF-sensing watch (AFSW; Apple Watch with KardiaBand) with simultaneous recordings from an insertable cardiac monitor (ICM; Reveal LINQ).

Methods:
SmartRhythm 2.0, a convolutional neural network, was trained on anonymized data of heart rate, activity level, and ECGs from 7500 AliveCor users. The network was validated on data collected in 24 patients with ICMs and a history of paroxysmal AF who simultaneously wore the AFSW with SmartRhythm 0.1 software. The primary outcome was sensitivity of the AFSW for AF episodes ≥1 hour. Secondary end points included sensitivity of the AFSW for detection of AF by subject and sensitivity for total AF duration across all subjects. Subjects with >50% false-positive AF episodes on ICM were excluded.

Results:
We analyzed 31 348.9 hours (mean (SD), 11.3 (4.4) hours/day) of simultaneous AFSW and ICM recordings in 24 patients. The ICM detected 82 episodes of AF ≥1 hour while the AFSW was worn, with a total duration of 1127.1 hours. Of these, the SmartRhythm 2.0 neural network detected 80 episodes (episode sensitivity, 97.5%) with a total duration of 1101.1 hours (duration sensitivity, 97.7%). Three of the 18 subjects with AF ≥1 hour had AF only when the watch was not being worn (patient sensitivity, 83.3%; or 100% during time worn). Positive predictive value for AF episodes was 39.9%.

Conclusions:
An AFSW is highly sensitive for detection of AF and assessment of AF duration in an ambulatory population when compared with an ICM. Such devices may represent an inexpensive, noninvasive approach to long-term AF surveillance and management.
Effects of competition, female size, and their distance on the claw-waving rate of male fiddler crabs (Brachyura, Ocypodidae)
Authors: Tina Fahmida Wazed 
Published: May 2019

Abstract
The alteration of signals of animals in response to changes in environmental factors is a common phenomenon. In male fiddler crabs, waving major claws towards females is energetically costly; thus, males need to adjust their waving in a way that increases the chance of potential mate attraction while reducing the waving cost. In this study, I examined how Austruca perplexa males adjusted their waving rate based on male-male competition (male numbers in a cluster [Austruca perplexa males make groups and wave synchronously towards females]), female body size, and the distances of the receiver females from the signaller males. Forty clusters were selected randomly; from each cluster, I randomly selected one male, video recorded his waving behaviour and calculated waving rate (waves/min). Body size (carapace width) and distances of receiver females were measured. To analyze the effects of competition, female size, and their distances on male waving rate through binary logistic regression analysis, all variables were divided into two categories (male waving rate: low and high, competition: low and high, female size: small and large, and female distances: short and long) based on a median split method. Afterwards a series of binary logistic regression models were built and the relative supports of various models were assessed based on the corrected Akaike information criterion. Results showed that competition, female body size and their distances affected the male waving rate in an additive manner, but their interactions did not show any effect. Further research can be conducted to investigate how breeding season and predation risk along with competition, female size and female distances affect the claw-waving display of male fiddler crabs.
How Well Do Operational Numerical Weather Prediction Configurations Represent Hydrology?
Authors: Zsoter Ervin , Cloke Hannah , Stephens Elisabeth , de Rosnay Patricia , Muñoz-Sabater Joaquin , Prudhomme Christel , Pappenberger Florian 
Published: May 2019

Abstract
Land surface models (LSMs) have traditionally been designed to focus on providing lower-boundary conditions to the atmosphere with less focus on hydrological processes. State-of-the-art application of LSMs includes a land data assimilation system (LDAS), which incorporates available land surface observations to provide an improved realism of surface conditions. While improved representations of the surface variables (such as soil moisture and snow depth) make LDAS an essential component of any numerical weather prediction (NWP) system, the related increments remove or add water, potentially having a negative impact on the simulated hydrological cycle by opening the water budget. This paper focuses on evaluating how well global NWP configurations are able to support hydrological applications, in addition to the traditional weather forecasting. River discharge simulations from two climatological reanalyses are compared: one “online” set, which includes land–atmosphere coupling and LDAS with an open water budget, and an “offline” set with a closed water budget and no LDAS. It was found that while the online version of the model largely improves temperature and snow depth conditions, it causes poorer representation of peak river flow, particularly in snowmelt-dominated areas in the high latitudes. Without addressing such issues there will never be confidence in using LSMs for hydrological forecasting applications across the globe. This type of analysis should be used to diagnose where improvements need to be made; considering the whole Earth system in the data assimilation and coupling developments is critical for moving toward the goal of holistic Earth system approaches.
Human and Climate Effects on the Hamoun Wetlands
Authors: Maleki Saeideh , Koupaei Saeid Soltani , Soffianian Alireza , Saatchi Sassan , Pourmanafi Saeid , Rahdari Vahid 
Published: May 2019

Abstract
Negative impacts of climate change on ecosystems have been increasing, and both the intensification and the mitigation of these impacts are strongly linked with human activities. Management and reduction of human-induced disturbances on ecosystems can mitigate the effects of climate change and enhance the ecosystem recovery process. Here, we investigate coupled human and climate effects on the wetland ecosystem of the lower Helmand basin from 1977 to 2014. Using time series climate-variable data and land-use changes from Landsat time series imagery, we compared changes in ecosystem status between the upstream and downstream regions. Results show that despite a strong and prolonged drought in the region, the upstream region of the lower Helmand basin remained dominated by agriculture, causing severe water stress on the Hamoun wetlands downstream. The loss of available water in wetlands was followed by large-scale land abandonment in rural areas, migration to the cities, and increasing unemployment and economic hardship. Our results suggest that unsustainable land-use policies in the upstream region, combined with synergistic effects of human activities and climate in lower Helmand basin, have exacerbated the effects of water stress on local inhabitants in the downstream region.
Outcomes of endoscopic submucosal dissection for early oesophageal squamous cell neoplasia at a Western centre
Authors: Lorenzo Diane , Barret Maximilien , Leblanc Sarah , Terris Benoit , Beuvon Frédéric , Coriat Romain , Chaussade Stanislas , Prat Frédéric 
Published: May 2019

Background and aimsEndoscopic submucosal dissection is the reference treatment for early oesophageal squamous cell carcinoma. However, data from Western centres are scarce.MethodsWe conducted a retrospective study from a prospectively collected database at a tertiary care centre in France. All consecutive patients undergoing endoscopic submucosal dissection for oesophageal squamous cell carcinoma were included. The main outcome was the curative resection rate. Secondary outcomes were en‐bloc resection rates, histologically complete resection rates, morbidity, recurrence‐free and overall survival.ResultsFifty‐six cases of oesophageal squamous cell carcinoma (49 patients; mean age 61.5 ± 10 years; 36 men) were included. En‐bloc, histologically complete and curative resection rates were 98%, 86% and 71%, respectively. Fifteen (30%) patients received an additional treatment after endoscopic submucosal dissection, nine treated by chemoradiotherapy, four by surgery and two by further endoscopic submucosal dissection. Within a mean follow‐up of 21 ± 15 months, recurrences occurred in 14 (29%) patients (four local, eight metachronous and three distant recurrences). Eight patients died during follow‐up, of which two (4%) patients died from oesophageal squamous cell carcinoma. Factors significantly associated with mortality in this series were: moderate or poor differentiation of oesophageal squamous cell carcinoma (p = 0.02) and recurrence of oesophageal squamous cell carcinoma (p = 0.028).ConclusionModerately or poorly differentiated cancer is a major prognostic factor and should probably be taken into account when indicating an additional treatment after endoscopic submucosal dissection. Close endoscopic follow‐up is essential considering the high recurrence rate.
Biobanking in health care: evolution and future directions
Authors: Coppola Luigi , Cianflone Alessandra , Grimaldi Anna Maria , Incoronato Mariarosaria , Bevilacqua Paolo , Messina Francesco , Baselice Simona , Soricelli Andrea , Mirabelli Peppino , Salvatore Marco 
Published: May 2019

AbstractBackgroundThe aim of the present review is to discuss how the promising field of biobanking can support health care research strategies. As the concept has evolved over time, biobanks have grown from simple biological sample repositories to complex and dynamic units belonging to large infrastructure networks, such as the Pan-European Biobanking and Biomolecular Resources Research Infrastructure (BBMRI). Biobanks were established to support scientific knowledge. Different professional figures with varied expertise collaborate to obtain and collect biological and clinical data from human subjects. At same time biobanks preserve the human and legal rights of each person that offers biomaterial for research.MethodsA literature review was conducted in April 2019 from the online database PubMed, accessed through the Bibliosan platform. Four primary topics related to biobanking will be discussed: (i) evolution, (ii) bioethical issues, (iii) organization, and (iv) imaging.ResultsMost biobanks were founded as local units to support specific research projects, so they evolved in a decentralized manner. The consequence is an urgent needing for procedure harmonization regarding sample collection, processing, and storage. Considering the involvement of biomaterials obtained from human beings, different ethical issues such as the informed consent model, sample ownership, veto rights, and biobank sustainability are debated. In the face of these methodological and ethical challenges, international organizations such as BBMRI play a key role in supporting biobanking activities. Finally, a unique development is the creation of imaging biobanks that support the translation of imaging biomarkers (identified using a radiomic approach) into clinical practice by ensuring standardization of data acquisition and analysis, accredited technical validation, and transparent sharing of biological and clinical data.ConclusionModern biobanks permit large-scale analysis for individuation of specific diseases biomarkers starting from biological or digital material (i.e., bioimages) with well-annotated clinical and biological data. These features are essential for improving personalized medical approaches, where effective biomarker identification is a critical step for disease diagnosis and prognosis.
Investigation of pore structure characteristics of marine organic-rich shales using low-pressure N2 adsorption experiments and fractal theory
Authors: Zhao Difei , Yin Shuai , Guo Yinghai , Ren Chengyao , Wang Ruyue , Dinge Wenlong , Liue Jingshou 
Published: May 2019

The pore structure and fractal characteristics of the Lower Cambrian marine organic-rich shale in southern China were comprehensively studied using low-pressure [Formula: see text] adsorption and organic geochemical experiments, X-ray diffraction, petrophysical property tests, and scanning electron microscope observations. The results indicate that the total organic carbon (TOC) content of the study shale varies between 0.45% and 8.50%, with an average value of 3.97%. The adsorption isotherm of the shale samples belongs to type IV, and slit-type pores are the predominant pore type in these shales. The shale has a Brunner–Emmet–Teller specific surface area ranging from 1.83 to [Formula: see text], a pore volume ranging from 0.00398 to [Formula: see text], and an average pore diameter ranging from 3.61 to 15.19 nm. Organic matter pores (OMPs) are the main contributors to the specific surface area and the pore volume. The organic matter is closely symbiotic with the epigenetic quartz. We have obtained two fractal dimensions ([Formula: see text] and [Formula: see text]) of the shale using the Frenkel-Halsey-Hill method. It was found that [Formula: see text] is suitable for the quantitative characterizing of the pore structure of nanopores inside the shale due to its good correlation with the TOC content and pore structure parameters. When the TOC content of the shale exceeds 4%, the main pore type inside the shale is OMP and the [Formula: see text] value mainly reflects the fractal characteristics of OMP. Moreover, we analyzed the seepage characteristics of different types of pores. It was found that the parallel plate-like pores and the slit-type pores are more favorable for fluid seepage than the ink bottle-like pores. The shale with [Formula: see text] and [Formula: see text] type pore structures should be the key exploration targets for the target shale in the study area.
Closure beyond clozapine: successfully averting rebound symptoms in a patient with schizoaffective disorder and agranulocytosis
Authors: Green Alastair , Stephenson Thomas , Whiskey Eromona , Shergill Sukhi S. 
Published: May 2019

Summary
‘Rebound’ or ‘withdrawal’ symptoms are frequently observed after a sudden discontinuation of clozapine. We describe a patient with treatment-resistant schizoaffective disorder who developed agranulocytosis on clozapine but was successfully switched to treatment with olanzapine with no deterioration in her condition. We put forward three possible theories which may have accounted for the lack of rebound symptoms in this patient: the pharmacological profile of olanzapine, the anticholinergic effects of hyoscine hydrobromide, and the possibility that this patient may not be treatment-resistant and so have a reduced risk of rebound psychosis due to displaying a different pathophysiology.

Declaration of interest
None.
The molecular anatomy of mammalian upper lip and primary palate fusion at single cell resolution
Authors: Li Hong , Jones Kenneth L. , Hooper Joan E. , Williams Trevor 
Published: May 2019

ABSTRACT
The mammalian lip and primary palate form when coordinated growth and morphogenesis bring the nasal and maxillary processes into contact, and the epithelia co-mingle, remodel and clear from the fusion site to allow mesenchyme continuity. Although several genes required for fusion have been identified, an integrated molecular and cellular description of the overall process is lacking. Here, we employ single cell RNA sequencing of the developing mouse face to identify ectodermal, mesenchymal and endothelial populations associated with patterning and fusion of the facial prominences. This analysis indicates that key cell populations at the fusion site exist within the periderm, basal epithelial cells and adjacent mesenchyme. We describe the expression profiles that make each population unique, and the signals that potentially integrate their behaviour. Overall, these data provide a comprehensive high-resolution description of the various cell populations participating in fusion of the lip and primary palate, as well as formation of the nasolacrimal groove, and they furnish a powerful resource for those investigating the molecular genetics of facial development and facial clefting that can be mined for crucial mechanistic information concerning this prevalent human birth defect.