bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fusion proteins with chromogenic and keratin binding modules
Authors: Tinoco Ana , Antunes Egipto , Martins Madalena , Gonçalves Filipa , Gomes Andreia C. , Silva Carla , Cavaco-Paulo Artur , Ribeiro Artur 
Published: October 2019

AbstractThe present research relates to a fusion protein comprising a chromogenic blue ultramarine protein (UM) bound to a keratin-based peptide (KP). The KP-UM fusion protein explores UM chromogenic nature together with KP affinity towards hair. For the first time a fusion protein with a chromogenic nature is explored as a hair coloring agent. The KP-UM protein colored overbleached hair, being the color dependent on the formulation polarity. The protein was able to bind to the hair cuticle and even to penetrate throughout the hair fibre. Molecular dynamics studies demonstrated that the interaction between the KP-UM protein and the hair was mediated by the KP sequence. All the formulations recovered the mechanical properties of overbleached hair and KP-UM proved to be safe when tested in human keratinocytes. Although based on a chromogenic non-fluorescent protein, the KP-UM protein presented a photoswitch phenomenon, changing from chromogenic to fluorescent depending on the wavelength selected for excitation. KP-UM protein shows the potential to be incorporated in new eco-friendly cosmetic formulations for hair coloration, decreasing the use of traditional dyes and reducing its environmental impact.
Head and Neck Cancer Detection in Digitized Whole-Slide Histology Using Convolutional Neural Networks
Authors: Halicek Martin , Shahedi Maysam , Little James V. , Chen Amy Y. , Myers Larry L. , Sumer Baran D. , Fei Baowei 
Published: October 2019

AbstractPrimary management for head and neck cancers, including squamous cell carcinoma (SCC), involves surgical resection with negative cancer margins. Pathologists guide surgeons during these operations by detecting cancer in histology slides made from the excised tissue. In this study, 381 digitized, histological whole-slide images (WSI) from 156 patients with head and neck cancer were used to train, validate, and test an inception-v4 convolutional neural network. The proposed method is able to detect and localize primary head and neck SCC on WSI with an AUC of 0.916 for patients in the SCC testing group and 0.954 for patients in the thyroid carcinoma testing group. Moreover, the proposed method is able to diagnose WSI with cancer versus normal slides with an AUC of 0.944 and 0.995 for the SCC and thyroid carcinoma testing groups, respectively. For comparison, we tested the proposed, diagnostic method on an open-source dataset of WSI from sentinel lymph nodes with breast cancer metastases, CAMELYON 2016, to obtain patch-based cancer localization and slide-level cancer diagnoses. The experimental design yields a robust method with potential to help create a tool to increase efficiency and accuracy of pathologists detecting head and neck cancers in histological images.
Balanced cholinergic modulation of spinal locomotor circuits via M2 and M3 muscarinic receptors
Authors: Nascimento Filipe , Spindler Lennart R. B. , Miles Gareth B. 
Published: October 2019

AbstractNeuromodulation ensures that neural circuits produce output that is flexible whilst remaining within an optimal operational range. The neuromodulator acetylcholine is released during locomotion to regulate spinal motor circuits. However, the range of receptors and downstream mechanisms by which acetylcholine acts have yet to be fully elucidated. We therefore investigated metabotropic acetylcholine receptor-mediated modulation by using isolated spinal cord preparations from neonatal mice in which locomotor-related output can be induced pharmacologically. We report that M2 receptor blockade decreases the frequency and amplitude of locomotor-related activity, whilst reducing its variability. In contrast, M3 receptor blockade destabilizes locomotor-related bursting. Motoneuron recordings from spinal cord slices revealed that activation of M2 receptors induces an outward current, decreases rheobase, reduces the medium afterhyperpolarization, shortens spike duration and decreases synaptic inputs. In contrast, M3 receptor activation elicits an inward current, increases rheobase, extends action potential duration and increases synaptic inputs. Analysis of miniature postsynaptic currents support that M2 and M3 receptors modulate synaptic transmission via different mechanisms. In summary, we demonstrate that M2 and M3 receptors have opposing modulatory actions on locomotor circuit output, likely reflecting contrasting cellular mechanisms of action. Thus, intraspinal cholinergic systems mediate balanced, multimodal control of spinal motor output.
High-affinity Cu(I) chelator PSP-2 as potential anti-angiogenic agent
Authors: Heuberger Dorothea M. , Harankhedkar Shefali , Morgan Thomas , Wolint Petra , Calcagni Maurizio , Lai Barry , Fahrni Christoph J. , Buschmann Johanna 
Published: October 2019

AbstractCopper is an essential trace metal that has been implicated in angiogenesis, the formation of new blood vessels. As tumor growth relies on establishing a functional capillary network for blood supply, copper chelation therapy may hold promise as an anti-cancer strategy by suppressing angiogenesis. To test the anti-angiogenic effect of PSP-2, a recently developed high affinity Cu(I) chelator with low zeptomolar dissociation constant, we utilized the endothelial cancer cell line EAhy926 and assessed changes in cell migration, proliferation, and tube formation in Matrigel. In addition, sprouting was assessed by the chicken and sheep aortic ring assay, and vascular pattern formation was studied in the chorioallantoic membrane of chicken embryos (CAM assay). While incubation with PSP-2 resulted in selective depletion of cellular copper levels, cell migration was not affected and the proliferating activity was even slightly increased. Moreover, the endothelial tube formation assay revealed significant morphological changes in the presence of PSP-2, with thicker tubular walls and an overall decreased meshes area. Similarly, the aortic ring assay and CAM assay showed that PSP-2 evokes significantly longer sprouts with smaller angles at branching points. Altogether, PSP-2 exhibits significant bioactivity at concentrations as low as 5 μM, rendering it a promising anti-angiogenic agent. As EAhy926 cells exhibit both endothelial and tumorigenic properties, the anti-angiogenic effect of PSP-2 might potentially translate also into anti-cancer activity.
The functional ClpXP protease of Chlamydia trachomatis requires distinct clpP genes from separate genetic loci
Authors: Pan Stefan , Malik Imran T. , Thomy Dhana , Henrichfreise Beate , Sass Peter 
Published: October 2019

AbstractClp proteases play a central role in bacterial physiology and, for some bacterial species, are even essential for survival. Also due to their conservation among bacteria including important human pathogens, Clp proteases have recently attracted considerable attention as antibiotic targets. Here, we functionally reconstituted and characterized the ClpXP protease of Chlamydia trachomatis (ctClpXP), an obligate intracellular pathogen and the causative agent of widespread sexually transmitted diseases in humans. Our in vitro data show that ctClpXP is formed by a hetero-tetradecameric proteolytic core, composed of two distinct homologs of ClpP (ctClpP1 and ctClpP2), that associates with the unfoldase ctClpX via ctClpP2 for regulated protein degradation. Antibiotics of the ADEP class interfere with protease functions by both preventing the interaction of ctClpX with ctClpP1P2 and activating the otherwise dormant proteolytic core for unregulated proteolysis. Thus, our results reveal molecular insight into ctClpXP function, validating this protease as an antibacterial target.
VDAC1 is essential for neurite maintenance and the inhibition of its oligomerization protects spinal cord from demyelination and facilitates locomotor function recovery after spinal cord injury
Authors: Paschon Vera , Morena Beatriz Cintra , Correia Felipe Fernandes , Beltrame Giovanna Rossi , dos Santos Gustavo Bispo , Cristante Alexandre Fogaça , Kihara Alexandre Hiroaki 
Published: October 2019

AbstractDuring the progression of the neurodegenerative process, mitochondria participates in several intercellular signaling pathways. Voltage-dependent anion-selective channel 1 (VDAC1) is a mitochondrial porin involved in the cellular metabolism and apoptosis intrinsic pathway in many neuropathological processes. In spinal cord injury (SCI), after the primary cell death, a secondary response that comprises the release of pro-inflammatory molecules triggers apoptosis, inflammation, and demyelination, often leading to the loss of motor functions. Here, we investigated the functional role of VDAC1 in the neurodegeneration triggered by SCI. We first determined that in vitro targeted ablation of VDAC1 by specific morpholino antisense nucleotides (MOs) clearly promotes neurite retraction, whereas a pharmacological blocker of VDAC1 oligomerization (4, 4′-diisothiocyanatostilbene-2, 2′-disulfonic acid, DIDS), does not cause this effect. We next determined that, after SCI, VDAC1 undergoes conformational changes, including oligomerization and N-terminal exposition, which are important steps in the triggering of apoptotic signaling. Considering this, we investigated the effects of DIDS in vivo application after SCI. Interestingly, blockade of VDAC1 oligomerization decreases the number of apoptotic cells without interfering in the neuroinflammatory response. DIDS attenuates the massive oligodendrocyte cell death, subserving undisputable motor function recovery. Taken together, our results suggest that the prevention of VDAC1 oligomerization might be beneficial for the clinical treatment of SCI.
Antileukemic activity of novel adenosine derivatives
Authors: Poczta Anastazja , Rogalska Aneta , Łukawska Małgorzata , Marczak Agnieszka 
Published: October 2019

AbstractThe present study investigated the effect of cladribine (CLA) and six of its derivatives containing a formamidine group at position 6 (CLA-FDM, CLA-FPAZ, CLA-FPIR, CLA-FPIP, CLA-FHEX, and CLA-FMOR) on acute promyelocytic, lymphoblastic, and acute monocytic leukemia cells. The role of ATR kinase in deoxycytidine kinase (dCK) activation in response to DNA damage was assessed. The presence of DNA lesions was assessed by measurement phosphorylation of H2AX and by using the alkaline comet assay with proteinase K post-treatment following assessment of the cell cycle. Apoptotic events such as alterations in intracellular calcium concentration, caspase-3/7 activity and increased sub-G1 cell population were measured. CLA derivatives were highly effective against leukemic cells, showing high cytotoxicity, causing DNA fragmentation, and inducing DNA-protein cross-links in leukemic cells. CLA-FMOR showed the highest efficacy. CLA derivatives increased the levels of intracellular calcium ions, caspase-3/7 and the percentage of sub-G1 apoptotic cells and blocked cells in the S phase of the cell cycle to a greater extent than free CLA. The selective ATR inhibitor VE-821 significantly suppressed the increase in dCK activity and decreased basal dCK activity. The present results suggested that ATR kinase controls dCK activity in response to synthetic CLA derivatives.
Earth-Gravity Congruent Motion Facilitates Ocular Control for Pursuit of Parabolic Trajectories
Authors: Jörges Björn , López-Moliner Joan 
Published: October 2019

AbstractThere is evidence that humans rely on an earth gravity (9.81 m/s²) prior for a series of tasks involving perception and action, the reason being that gravity helps predict future positions of moving objects. Eye-movements in turn are partially guided by predictions about observed motion. Thus, the question arises whether knowledge about gravity is also used to guide eye-movements: If humans rely on a representation of earth gravity for the control of eye movements, earth-gravity-congruent motion should elicit improved visual pursuit. In a pre-registered experiment, we presented participants (n = 10) with parabolic motion governed by six different gravities (−1/0.7/0.85/1/1.15/1.3 g), two initial vertical velocities and two initial horizontal velocities in a 3D environment. Participants were instructed to follow the target with their eyes. We tracked their gaze and computed the visual gain (velocity of the eyes divided by velocity of the target) as proxy for the quality of pursuit. An LMM analysis with gravity condition as fixed effect and intercepts varying per subject showed that the gain was lower for −1 g than for 1 g (by −0.13, SE = 0.005). This model was significantly better than a null model without gravity as fixed effect (p < 0.001), supporting our hypothesis. A comparison of 1 g and the remaining gravity conditions revealed that 1.15 g (by 0.043, SE = 0.005) and 1.3 g (by 0.065, SE = 0.005) were associated with lower gains, while 0.7 g (by 0.054, SE = 0.005) and 0.85 g (by 0.029, SE = 0.005) were associated with higher gains. This model was again significantly better than a null model (p < 0.001), contradicting our hypothesis. Post-hoc analyses reveal that confounds in the 0.7/0.85/1/1.15/1.3 g condition may be responsible for these contradicting results. Despite these discrepancies, our data thus provide some support for the hypothesis that internalized knowledge about earth gravity guides eye movements.
Speckleplethysmographic (SPG) Estimation of Heart Rate Variability During an Orthostatic Challenge
Authors: Dunn Cody E. , Monroe Derek C. , Crouzet Christian , Hicks James W. , Choi Bernard 
Published: October 2019

AbstractHeart rate variability (HRV) provides insight into cardiovascular health and autonomic function. Electrocardiography (ECG) provides gold standard HRV measurements but is inconvenient for continuous acquisition when monitored from the extremities. Optical techniques such as photoplethysmography (PPG), often found in health and wellness trackers for heart rate measurements, have been used to estimate HRV peripherally but decline in accuracy during increased physical stress. Speckleplethysmography (SPG) is a recently introduced optical technique that provides benefits over PPG, such as increased signal amplitude and reduced susceptibility to temperature-induced vasoconstriction. In this research, we compare SPG and PPG to ECG for estimation of HRV during an orthostatic challenge performed by 17 subjects. We find that SPG estimations of HRV are highly correlated to ECG HRV for both time and frequency domain parameters and provide increased accuracy over PPG estimations of HRV. The results suggest SPG measurements are a viable alternative for HRV estimation when ECG measurements are impractical.
Combining ddPCR and environmental DNA to improve detection capabilities of a critically endangered freshwater invertebrate
Authors: Mauvisseau Quentin , Davy-Bowker John , Bulling Mark , Brys Rein , Neyrinck Sabrina , Troth Christopher , Sweet Michael 
Published: October 2019

AbstractIsogenus nubecula is a critically endangered Plecoptera species. Considered extinct in the UK, I. nubecula was recently rediscovered (in one location of the River Dee, Wales), after 22 years of absence. In a similar way to many other species of Perlodidae, I. nubecula could be utilised as a bio-indicator, for assessing water quality and health status of a given freshwater system. However, conventional monitoring of invertebrates via kick-sampling, is invasive and expensive (time consuming). Further, such methods require a high level of taxonomic expertise. Here, we compared the traditional kick-sampling method with the use of eDNA detection using qPCR and ddPCR-analyses. In spring 2018, we sampled eDNA from twelve locations on the River Dee. I. nubecula was detected using kick-sampling in five of these locations, three locations using both eDNA detection and kick-sampling and one location using eDNA detection alone – resulting in a total of six known and distinct populations of this critically endangered species. Interestingly, despite the eDNA assay being validated in vitro and in silico, and results indicating high sensitivity, qPCR analysis of the eDNA samples proved to be ineffective. In contrast, ddPCR analyses resulted in a clear detection of I. nubecula at four locations suggesting that inhibition most likely explains the large discrepancy between the obtained qPCR and ddPCR results. It is therefore important to explore inhibition effects on any new eDNA assay. We also highlight that ddPCR may well be the best option for the detection of aquatic organisms which are either rare or likely to shed low levels of eDNA into their environment.
Explicit and implicit monitoring in neurodegeneration and stroke
Authors: Garcia-Cordero Indira , Sedeño Lucas , Babino Andrés , Dottori Martín , Melloni Margherita , Martorell Caro Miguel , Sigman Mariano , Herrera Eduar , Manes Facundo , García Adolfo M. , Ibáñez Agustín 
Published: October 2019

AbstractMonitoring is a complex multidimensional neurocognitive phenomenon. Patients with fronto-insular stroke (FIS), behavioural variant frontotemporal dementia (bvFTD) and Alzheimer’s disease (AD) show a lack of self-awareness, insight, and self-monitoring, which translate into anosognosia and daily behavioural impairments. Notably, they also present damage in key monitoring areas. While neuroscientific research on this domain has accrued in recent years, no previous study has compared monitoring performance across these brain diseases and none has applied a multiple lesion model approach combined with neuroimaging analysis. Here, we evaluated explicit and implicit monitoring in patients with focal stoke (FIS) and two types of dementia (bvFTD and AD) presenting damage in key monitoring areas. Participants performed a visual perception task and provided two types of report: confidence (explicit judgment of trust about their performance) and wagering (implicit reports which consisted in betting on their accuracy in the perceptual task). Then, damaged areas were analyzed via structural MRI to identify associations with potential behavioral deficits. In AD, inadequate confidence judgments were accompanied by poor wagering performance, demonstrating explicit and implicit monitoring impairments. By contrast, disorders of implicit monitoring in FIS and bvFTD patients occurred in the context of accurate confidence reports, suggesting a reduced ability to turn self-knowledge into appropriate wagering conducts. MRI analysis showed that ventromedial compromise was related to overconfidence, whereas fronto-temporo-insular damage was associated with excessive wagering. Therefore, joint assessment of explicit and implicit monitoring could favor a better differentiation of neurological profiles (frontal damage vs AD) and eventually contribute to delineating clinical interventions.
Broadband Microwave Absorption by Logarithmic Spiral Metasurface
Authors: Wang Shubo , Hou Bo , Chan Che Ting 
Published: October 2019

AbstractMetamaterials have enabled the design of electromagnetic wave absorbers with unprecedented performance. Conventional metamaterial absorbers usually employ multiple structure components in one unit cell to achieve broadband absorption. Here, a simple metasurface microwave absorber is proposed that has one metal-backed logarithmic spiral resonator as the unit cell. It can absorb >95% of normally incident microwave energy within the frequency range of 6 GHz–37 GHz as a result of the scale invariant geometry and the Fabry-Perot-type resonances of the resonator. The thickness of the metasurface is 5 mm and approaches the Rozanov limit of an optimal absorber. The physics underlying the broadband absorption is discussed. A comparison with Archimedean spiral metasurface is conducted to uncover the crucial role of scale invariance. The study opens a new direction of electromagnetic wave absorption by employing the scale invariance of Maxwell equations and may also be applied to the absorption of other classical waves such as sound.
Comparison of combined compression and surgery with high ligation-endovenous laser ablation-foam sclerotherapy with compression alone for active venous leg ulcers
Authors: Liu Xiaochun , Zheng Guofu , Ye Bo , Chen Weiqing , Xie Hailiang , Zhang Teng 
Published: October 2019

AbstractWe aimed to assess the ulcer healing time and recurrence rates after treatment with compression therapy (CT) with or without high ligation-endovenous laser ablation-foam sclerotherapy (HL-EVLA-FS) in people with active venous leg ulcers (VLUs). A retrospective cohort study was conducted with 350 patients with active VLUs treated by compression with or without HL-EVLA-FS in our hospital from 2013 to 2017. The primary outcome was the ulcer healing time; secondary outcomes were the 12-month recurrence rates, the relationship between recurrence and venous reflux, and the complications of the two treatments. In total, 193 patients (200 limbs) underwent compression plus HL-EVLA-FS, and 157 patients (177 limbs) underwent CT alone. The ulcer healing time was shorter in the compression plus HL-EVLA-FS group than in the CT alone group (Hazard Ratio [HR] for ulcer healing, 1.845 [95% CI, 1.474–2.309], P = 0.0001). The 12-month ulcer recurrence rates were significantly reduced in the compression plus HL-EVLA-FS group (HR for ulcer recurrence, 0.418 [95% CI, 0.258–0.677], P = 0.0001). Calf perforator vein reflux (CPVR) and isolated superficial venous reflux (ISVR) were risk factors for ulcer recurrence. The combined operation with CT resulted in faster healing of VLUs, a lower ulcer recurrence rate and lower VCSS values after intervention than CT alone.
Preoperative Somatostatin Analogues in Patients with Newly-diagnosed Acromegaly: A Systematic Review and Meta-analysis of Comparative Studies
Authors: Yang Chengxian , Li Ge , Jiang Shenzhong , Bao Xinjie , Wang Renzhi 
Published: October 2019

AbstractBiochemical remission after transsphenoidal surgery is still unsatisfied in acromegaly patients with macroadenomas, especially with invasive macroadenomas. Concerning the impact of preoperative somatostatin analogues (SSAs) on surgical outcomes, previous studies with limited cases reported conflicting results. To assess current evidence of preoperative medical treatment, we performed a systematic review and meta-analysis of comparative studies. A literature search was conducted in Pubmed, Embase, and the Cochrane Library. Five randomized controlled trials (RCT) and seven non-RCT comparative studies were included. These studies mainly focused on pituitary macroadenomas though a small number of microadenoma cases were included. For safety, preoperative SSAs were not associated with elevated risks of postoperative complications. With respect to efficacy, the short-term cure rate was improved by preoperative SSAs, but the long-term cure rate showed no significant improvement. For invasive macroadenomas, the short-term cure rate was also improved, but the long-term results were not evaluable in clinical practice because adjuvant therapy was generally required. In conclusion, preoperative SSAs are safe in patients with acromegaly, and the favorable impact on surgical results is restricted to the short-term cure rate in macroadenomas and invasive macroadenomas. Further well-designed RCTs to examine long-term results are awaited to update the finding of this meta-analysis.