bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing the role of androgen deprivation therapy in advanced prostate cancer: Challenges beyond the guidelines
Authors: Shore Neal D. , Antonarakis Emmanuel S. , Cookson Michael S. , Crawford E. David , Morgans Alicia K. , Albala David M. , Hafron Jason , Harris Richard G. , Saltzstein Daniel , Brown Gordon A. , Henderson Jonathan , Lowentritt Benjamin , Spier Jeffrey M. , Concepcion Raoul 
Published: March 2020

AbstractBackgroundFor specific clinical indications, androgen deprivation therapy (ADT) will induce disease prostate cancer (PC) regression, relieve symptoms and prolong survival; however, ADT has a well‐described range of side effects, which may have a detrimental effect on the patient's quality of life, necessitating additional interventions or changes in PC treatment. The risk‐benefit analysis for initiating ADT in PC patients throughout the PC disease continuum warrants review.MethodsA 14‐member panel comprised of urologic and medical oncologists were chosen for an expert review panel, to provide guidance on a more judicious use of ADT in advanced PC patients. Panel members were chosen based upon their academic and community experience and expertise in the management of PC patients. Four academic members of the panel served as group leaders; the remaining eight panel members were from Large Urology Group Practice Association practices with proven experience in leading their advanced PC clinics. The panel members were assigned to four separate working groups, and were tasked with addressing the role of ADT in specific PC settings.ResultsThis article describes the practical recommendations of an expert panel for the use of ADT throughout the PC disease continuum, as well as an algorithm summarizing the key recommendations. The target for this publication is all providers (urologists, medical oncologists, radiation oncologists, or advanced practice providers) who evaluate and manage advanced PC patients, regardless of their practice setting.ConclusionThe panel has provided recommendations for monitoring PC patients while on ADT, recognizing that PC patients will progress despite testosterone suppression and, therefore, early identification of conversion from castrate‐sensitive to castration resistance is critical. Also, the requirement to both identify and mitigate side effects of ADT as well as the importance of quality of life maintenance are essential to the optimization of patient care, especially as more combinatorial therapeutic strategies with ADT continue to emerge.
Pathway-specific reporter genes to study stem cell biology
Authors: Peterson Karen M. , Franchi Federico , Olthoff Michaela , Chen Ian Y. , Paulmurugan Ramasamy , Rodriguez-Porcel Martin 
Published: March 2020

Abstract
Little is known on the phenotypic characteristics of stem cells (SCs) after they are transplanted to the myocardium, in part due to lack of noninvasive platforms to study SCs directly in the living subject. Reporter gene imaging has played a valuable role in the noninvasive assessment of cell fate in vivo. In this study, we validated a pathway-specific reporter gene that can be used to noninvasively image the phenotype of SCs transplanted to the myocardium. Rat mesenchymal SCs (MSCs) were studied for phenotypic evidence of myogenic characteristics under in vitro conditions. After markers of myogenic characteristics were identified, we constructed a reporter gene sensor, comprising the firefly luciferase (Fluc) reporter gene driven by the troponin T (TnT) promoter (cardio MSCs had threefold expression in polymerase chain reaction compared to control MSCs) using a two-step signal amplification strategy. MSCs transfected with TnT-Fluc were studied and validated under in vitro conditions, showing a strong signal after MSCs acquired myogenic characteristics. Lastly, we observed that cardio MSCs had higher expression of the reporter sensor compared to control cells (0.005 ± 0.0005 vs 0.0025 ± 0.0008 Tnt-Fluc/ubiquitin-Fluc, P &lt; .05), and that this novel sensor can detect the change in the phenotype of MSCs directly in the living subject. Pathway-specific reporter gene imaging allows assessment of changes in the phenotype of MSCs after delivery to the ischemic myocardium, providing important information on the phenotype of these cells. Imaging sensors like the one described here are critical to better understanding of the changes that SCs undergo after transplantation.
Hes1deficiency causes hematopoietic stem cell exhaustion
Authors: Ma Zhilin , Xu Jian , Wu Limei , Wang Junjie , Lin Qiqi , Chowdhury Fabliha A. , Mazumder Md. Habibul H. , Hu Gangqing , Li Xue , Du Wei 
Published: March 2020

AbstractThe transcriptional repressor Hairy Enhancer of Split 1 (HES1) plays an essential role in the development of many organs by promoting the maintenance of stem/progenitor cells, controlling the reversibility of cellular quiescence, and regulating both cell fate decisions. Deletion of Hes1 in mice results in severe defects in multiple organs and is lethal in late embryogenesis. Here we have investigated the role of HES1 in hematopoiesis using a hematopoietic lineage-specific Hes1 knockout mouse model. We found that while Hes1 is dispensable for steady-state hematopoiesis, Hes1-deficient hematopoietic stem cells (HSCs) undergo exhaustion under replicative stress. Loss of Hes1 upregulates the expression of genes involved in PPARγ signaling and fatty acid metabolism pathways, and augments fatty acid oxidation (FAO) in Hes1f/fVav1Cre HSCs and progenitors. Functionally, PPARγ targeting or FAO inhibition ameliorates the repopulating defects of Hes1f/fVav1Cre HSCs through improving quiescence in HSCs. Lastly, transcriptome analysis reveals that disruption of Hes1 in hematopoietic lineage alters expression of genes critical to HSC function, PPARγ signaling, and fatty acid metabolism. Together, our findings identify a novel role of HES1 in regulating stress hematopoiesis and provide mechanistic insight into the function of HES1 in HSC maintenance.
Photostimulation of cerebral and peripheral lymphatic functions
Authors: Semyachkina‐Glushkovskaya Oxana , Abdurashitov Arkady , Klimova Maria , Dubrovsky Alexander , Shirokov Alexander , Fomin Alexander , Terskov Andrey , Agranovich Ilana , Mamedova Aysel , Khorovodov Aleksandr , Vinnik Valeria , Blokhina Inna , Lezhnev Nikita , Shareef Ali E. , Kuzmina Anna , Sokolovski Sergey , Tuchin Valery , Rafailov Edik , Kurths Jurgen 
Published: March 2020

AbstractThe recently rediscovered meningeal lymphatic system (MLS) opens new insight into pathways of brain clearing and drainage functions that play an important role in neurorehabilitation. The development of breakthrough strategies for augmentation of MLS might be a promising therapeutic target for preventing of neurological diseases. Here we demonstrate photostimulation (PS, 1268 nm) of clearing and drainage function of MLS in healthy male mice. We uncover PS‐mediated increase of the mesenteric lymphatic permeability to fluorescent macrophages via a decrease of expression of tight junction and transendothelial resistance. In sum, our results clearly show PS stimulation of meningeal clearing and drainage functions as well as effects of PS on permeability of the lymphatic endothelium to macrophages. These findings open new strategies for alternative nonpharmacological therapy of brain diseases via PS modulation of lymphatic mechanisms of the homeostasis of central nervous system.
Humanitarian access, interrupted: dynamic near real-time network analytics and mapping for reaching communities in disaster-affected countries
Authors: Warnier Martijn , Alkema Vincent , Comes Tina , Van de Walle Bartel 
Published: March 2020

AbstractIn the immediate aftermath of a disaster, local and international aid organisations deploy to deliver life-saving aid to the affected population. Yet pre-disaster road maps and road transportation models do not capture disruptions to the transportation network caused by the disaster or the dynamic changes of the situation, resulting in uncertainty and inefficiency in planning and decision-making. The integration of data in near real time on the status of the road infrastructure in the affected region can help aid organisations to keep track of the rapidly shifting conditions on the ground and to assess the implications for their logistics planning and operations. In this paper, we present a rapid graph-theoretical reachability information system based on a combination of OpenStreetMap and open humanitarian data. The system supports logistics planning in determining road access to affected communities. We demonstrate the results of our approach in a case study on the 2018 earthquake in Papua New Guinea. Our findings show the reachability of affected communities depending on the actual status of the road network, allowing for the prioritization of targeted locations and the identification of alternative routes to get there.
Sub-micron structuring/texturing of diamond-like carbon-coated replication masters with a femtosecond laser
Authors: Michalek Aleksandra , Qi Shaojun , Batal Afif , Penchev Pavel , Dong Hanshan , See Tian Long , Dimov Stefan 
Published: March 2020

AbstractDiamond-like carbon (DLC) coatings have very attractive mechanical and tribological properties, i.e. high hardness, low friction and high wear resistance. Therefore, DLC is often used as a solid lubricant in moulds for injection moulding. Laser processing of DLC with ultrashort lasers, i.e. femtosecond lasers, can be performed both at micron and sub-micron scales, namely by producing laser-induced periodic surface structures (LIPSS). In this research, the effects of laser structuring/texturing on DLC properties are investigated. First, the laser-processing parameters were optimised to produce uniform LIPSS without damaging a thin DLC film and then the properties of the textured DLC-coated substrates were studied. It was determined that the tribological properties of the processed surfaces remained unchanged, but the hardness of the structured/textured DLC layers was reduced significantly. Although GAXRD and Raman spectroscopy did not show any significant crystallisation of the DLC coating after the laser irradiation, the analysis indicated that a thin graphitised layer had been formed on the surface as a result of the femtosecond laser processing.
The impact of laser surface treatment on the microstructure, wear resistance and hardness of the AlMg5 aluminum alloy
Authors: Pakieła Wojciech , Tanski Tomasz , Brytan Zbigniew , Chladek Grzegorz , Pakieła Katarzyna 
Published: March 2020

AbstractLight metal alloys due to several unique properties such as low density and high corrosion resistance are increasingly used in various technical applications, where the automotive industry is one of the most important sectors. The automotive applications use mostly aluminum alloys, where the strength to density ratio of the material plays a crucial factor. Unfortunately, relatively low mechanical properties limit their applications for parts where a high surface hardness and wear resistance is expected. The classic heat treatment of aluminum alloys can only in some limited ranges improve the bulk material properties. Despite this, surface treatment with laser processing has developed significantly over the past 20 years. The laser beam treatment allows the introduction of a wide range of alloying elements to the surface layer of an aluminum alloy and thus, as a result of the precipitation of numerous intermetallic phases, significantly increases hardness, and abrasion resistance. The purpose of this work was to modify the aluminum surface layer using high-power fiber laser (HPFL). During this process, a mixture of titanium and iron powders (90/10 wt.%) was introduced onto the surface of the AlMg5 alloy. The microhardness tests carried out by the Vickers method and tribological tests showed a significant increase in mechanical properties in the entire volume of the obtained layer. Research on light and scanning microscopy revealed fragmentation of primary precipitates and the formation of numerous intermetallic phases rich in titanium and aluminum.
Does cement augmentation of the screws in angular stable plating for proximal humerus fractures influence the radiological outcome: a retrospective assessment
Authors: Knierzinger Dominik , Crepaz-Eger Ulrich , Hengg Clemens , Kralinger Franz 
Published: March 2020

Abstract
Background
Screw-tip augmentation in angular stable plating offers new possibilities for the treatment of complex proximal humerus fractures. This retrospective analysis was performed to evaluate the radiological outcome of proximal humerus fractures treated with angular stable plates and additional screw-tip cement augmentation in patients over the age of 60.

Materials and methods
A retrospective single centre analysis was conducted from June 2013 to December 2016. The minimum follow-up time was set to 6 months after surgery. Anatomical reduction and fixation were evaluated in respect to reattached tuberosities to the head fragment and the adequate restoration of the calcar area not showing any valgus or varus malalignment. Complete fracture healing was determined 3 months after surgery. Any failures such as secondary displacement, primary screw perforation, intraarticular cement leakage and avascular necrosis of the humeral head with concomitant screw cut-out were assessed.

Results
In total, 24 patients (21 females; 3 males) at a median age of 77.5 (62–96) years were included. Five 2-part, twelve 3-part and seven 4-part fractures were detected. The measured median BMD value of 23 patients was 78.4 mg/cm3 (38.8–136.9 mg/cm3). Anatomical reduction was achieved in 50% of the patients. In most cases, the A level screws and the B1 screw were augmented with bone cement by a median of 7 (5–9) head screws used. Postoperative varus displacement was not detected in any of the patients. One patient (4.2%) sustained an early secondary displacement. Intraarticular cement leakage was detected in 3 patients (2 head-split fractures). Avascular necrosis of the humeral head was observed in 4 patients (16.7%). Revision surgery was necessary in four cases, using hemiarthroplasty twice and reverse shoulder arthroplasty the other two times.

Conclusion
Screw-tip augmentation in angular stable plating for proximal humerus fracture treatment showed a low secondary displacement rate of 4.2% in patients suffering from poor bone quality. Nevertheless, the occurrence of avascular necrosis of the humeral head with mainly severe fracture patterns observed in this study was higher compared to previously reported results in the literature. Cement augmentation in head-split fractures is not recommended, considering the high risk of an intraarticular cement leakage.
Effects of 21 days of bed rest and whey protein supplementation on plantar flexor muscle fatigue resistance during repeated shortening contractions
Authors: Bosutti Alessandra , Mulder Edwin , Zange Jochen , Bühlmeier Judith , Ganse Bergita , Degens Hans 
Published: March 2020

AbstractPurposeSpace flight and bed rest (BR) lead to a rapid decline in exercise capacity. Whey protein plus potassium bicarbonate diet-supplementation (NUTR) could attenuate this effect by improving oxidative metabolism. We evaluated the impact of 21-day BR and NUTR on fatigue resistance of plantar flexor muscles (PF) during repeated shortening contractions, and whether any change was related to altered energy metabolism and muscle oxygenation.MethodsTen healthy men received a standardized isocaloric diet with (n = 5) or without (n = 5) NUTR. Eight bouts of 24 concentric plantar flexions (30 s each bout) with 20 s rest between bouts were employed. PF muscle size was assessed by means of peripheral quantitative computed tomography. PF muscle volume was assessed with magnetic resonance imaging. PF muscle force, contraction velocity, power and surface electromyogram signals were recorded during each contraction, as well as energy metabolism (31P nuclear magnetic resonance spectroscopy) and oxygenation (near-infrared spectroscopy). Cardiopulmonary parameters were measured during an incremental cycle exercise test.ResultsBR caused 10–15% loss of PF volume that was partly recovered 3 days after re-ambulation, as a consequence of fluid redistribution. Unexpectedly, PF fatigue resistance was not affected by BR or NUTR. BR induced a shift in muscle metabolism toward glycolysis and some signs of impaired muscle oxygen extraction. NUTR did not attenuate the BR-induced-shift in energy metabolism.ConclusionsTwenty-one days’ BR did not impair PF fatigue resistance, but the shift to glycolytic metabolism and indications of impaired oxygen extraction may be early signs of developing reduced muscle fatigue resistance.
Human genetics and malaria resistance
Authors: Kariuki Silvia N. , Williams Thomas N. 
Published: March 2020

AbstractMalaria has been the pre-eminent cause of early mortality in many parts of the world throughout much of the last five thousand years and, as a result, it is the strongest force for selective pressure on the human genome yet described. Around one third of the variability in the risk of severe and complicated malaria is now explained by additive host genetic effects. Many individual variants have been identified that are associated with malaria protection, but the most important all relate to the structure or function of red blood cells. They include the classical polymorphisms that cause sickle cell trait, α-thalassaemia, G6PD deficiency, and the major red cell blood group variants. More recently however, with improving technology and experimental design, others have been identified that include the Dantu blood group variant, polymorphisms in the red cell membrane protein ATP2B4, and several variants related to the immune response. Characterising how these genes confer their effects could eventually inform novel therapeutic approaches to combat malaria. Nevertheless, all together, only a small proportion of the heritable component of malaria resistance can be explained by the variants described so far, underscoring its complex genetic architecture and the need for continued research.
Heat source of the 2014 phreatic eruption of Mount Ontake, Japan
Authors: Miyagi Isoji , Geshi Nobuo , Hamasaki Satoshi , Oikawa Teruki , Tomiya Akihiko 
Published: March 2020

AbstractWe present petrological evidence of the shallow magmatic processes that may have supplied heat and gas to the eruption of Mount Ontake, Japan, on 27 September 2014, which resulted in 63 fatalities. Ash from the eruption comprises primarily hydrothermally altered, white-toned rock fragments. However, the ash contains trace amounts (< 0.7 wt%) of vitreous less-altered particles (LAPs), which are only altered on their surfaces, suggesting rapid ascent through the hydrothermal system. The LAPs are classified into two categories: “glassy” and “crystalline.” Glassy LAPs comprise high-silica rhyolitic glass (74–83 wt% SiO2) with rounded quartz, chalcedony-free vesicles, and reversely zoned plagioclase (cores = 47 mol% An; rims = 70 mol% An), indicating magma re-heating. Crystalline LAPs have a groundmass-like texture that suggests eutectic crystallization at shallow depths. Thermodynamic calculations indicate that the pre-eruptive temperatures of the glassy and crystalline LAPs were 700–1300 °C and ~ 700 °C, respectively, and that the storage depth was < 4 km (pressure < 100 MPa). The observed petrological features suggest that the LAPs were sourced from a magma recently intruded at shallow depths. Although crustal deformation (i.e., the volume change associated with magmatic intrusion) was insignificant prior to the 2014 eruption, a clear signature of crustal deformation was observed in 2007, the source of which was located 3 km below the summit. We suggest that the magma that was intruded 3 km below the summit in 2007 supplied the heat and gas for the 2014 phreatic eruption.
Objective evaluation for treat to target in Crohn’s disease
Authors: Takenaka Kento , Kitazume Yoshio , Fujii Toshimitsu , Tsuchiya Kiichiro , Watanabe Mamoru , Ohtsuka Kazuo 
Published: March 2020

AbstractBackgroundCrohn’s disease (CD) is a chronic and destructive bowel disease; continued disease activity can lead to penetrating complications. With the recent advent of effective medications, the importance of using a treat-to-target approach to guide therapy is becoming important.MethodsIn this review, we reviewed the previous evidence for evaluating CD lesions.ResultsWe describe ileocolonoscopy’s role in assessing disease activity, as well as recent progress in modalities, such as balloon-assisted endoscopy, capsule endoscopy, magnetic resonance enterography, computed tomography enterography, and ultrasonography. Advances in modalities have changed CD assessment, with small-bowel involvement becoming more important.ConclusionsProper optimization is necessary in clinical practice.
Health-related quality of life associated with trifluridine/tipiracil in heavily pretreated metastatic gastric cancer: results from TAGS
Authors: Tabernero Josep , Alsina Maria , Shitara Kohei , Doi Toshihiko , Dvorkin Mikhail , Mansoor Wasat , Arkenau Hendrik-Tobias , Prokharau Aliaksandr , Ghidini Michele , Faustino Catia , Gorbunova Vera , Zhavrid Edvard , Nishikawa Kazuhiro , Ando Takayuki , Yalçın Şuayib , Van Cutsem Eric , Sabater Javier , Skanji Donia , Leger Catherine , Amellal Nadia , Ilson David H. 
Published: March 2020

Abstract
Background
In TAGS, an international, double-blind, phase 3 trial, trifluridine/tipiracil significantly improved overall survival and progression-free survival compared with placebo in heavily pretreated metastatic gastric cancer patients. This paper reports pre-specified quality of life (QoL) outcomes for TAGS.

Methods
Patients were randomized 2:1 to trifluridine/tipiracil (35 mg/m2 twice daily on days 1–5 and 8–12 of each 28-day cycle) plus best supportive care (BSC) or placebo plus BSC. QoL was evaluated at baseline and at each treatment cycle, using the EORTC QLQ-C30 and EORTC QLQ-STO22 questionnaires; results were considered valid for analysis only if ≥ 10% of patients completed the questionnaires. Key QoL outcomes were mean changes from baseline and time to deterioration in QoL. A post hoc analysis assessed the association between QoL and time to deterioration of Eastern Cooperative Oncology Group performance score (ECOG PS) to ≥ 2.

Results
Of 507 randomized patients, 496 had baseline QoL data available. The analysis cut-off was 6 cycles for trifluridine/tipiracil and 3 cycles for placebo. In both treatment groups, there were no clinically significant deteriorations in the mean QLQ-C30 Global Health Status (GHS) score, or in most subscale scores. In a sensitivity analysis including death and disease progression as events, there was a trend towards trifluridine/tipiracil reducing the risk of deterioration of QoL scores compared with placebo. Deterioration in the GHS score was associated with deterioration in ECOG PS.

Conclusion
QoL was maintained in TAGS, and there was a trend towards trifluridine/tipiracil reducing the risk of QoL deterioration compared with placebo.
Trial registration ClinicalTrials.gov number: NCT02500043