bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient‐reported pain severity and health‐related quality of life in patients with multiple myeloma in real world clinical practice
Authors: Ludwig Heinz , Bailey Abigail Lucy , Marongiu Andrea , Khela Keerun , Milligan Gary , Carlson Katherine Brewer , Rider Alex , Seesaghur Anouchka 
Published: June 2021

AbstractBackgroundThe association between patient self‐reported pain severity and health‐related quality‐of‐life (HRQoL) is poorly understood.AimsThis real‐world study of symptomatic multiple myeloma (MM) patients sought to determine how pain severity from a single question asked during routine clinical consultation was associated with HRQoL.Methods and resultsPoint‐in‐time data on HRQoL of 330 patients with MM (median age 70 years) receiving anti‐myeloma therapy in Germany and Italy from November 2017 through February 2018 were analyzed. HRQoL was assessed using validated questionnaires (Work Productivity and Activity Impairment [WPAI], European Organization for Research and Treatment of Cancer Quality of Life Questionnaire ‐C30 and ‐MY20). Physical pain severity was assessed during clinical consultation by a single question, asking patients to describe their pain as “no pain,” “mild,” “moderate,” or “severe.” Associations between patient‐reported pain severity and HRQoL scores were assessed by analysis of variance or χ2 tests. Ninety‐six of the 330 patients (29.1%) reported moderate to severe pain. Increase in pain severity, from “no” to “severe” pain, was associated with significantly decreased overall HRQoL (mean score 70.2 to 33.3); significant decreases in levels of physical (82.7 to 35.1), social (81.1 to 44.4), emotional (78.1 to 48.3), and role functioning (79.5 to 38.9); and increased levels of WPAI usual activity impairment (35.4 to 71.4), and fatigue burden (26.0 to 68.9) (all p < .001).ConclusionHigher pain severity, based on a single self‐report question, was associated with poorer HRQoL in patients with MM, thereby supporting the clinical relevance of directly asking patients to self‐evaluate their pain severity.
Reducing Non‐Radiative Voltage Losses by Methylation of Push–Pull Molecular Donors in Organic Solar Cells
Authors: Baisinger Lukasz , Andrés Castán José María , Simón Marqués Pablo , Londi Giacomo , Göhler Clemens , Deibel Carsten , Beljonne David , Cabanetos Clément , Blanchard Philippe , Benduhn Johannes , Spoltore Donato , Leo Karl 
Published: June 2021

AbstractOrganic solar cells are approaching power conversion efficiencies of other thin‐film technologies. However, in order to become truly market competitive, the still substantial voltage losses need to be reduced. Here, the synthesis and characterization of four novel arylamine‐based push‐pull molecular donors was described, two of them exhibiting a methyl group at the para‐position of the external phenyl ring of the arylamine block. Assessing the charge‐transfer state properties and the effects of methylation on the open‐circuit voltage of the device showed that devices based on methylated versions of the molecular donors exhibited reduced voltage losses due to decreased non‐radiative recombination. Modelling suggested that methylation resulted in a tighter interaction between donor and acceptor molecules, turning into a larger oscillator strength to the charge‐transfer states, thereby ensuing reduced non‐radiative decay rates.
Routing protocols & unmanned aerial vehicles autonomous localization in flying networks
Authors: Khan Inam Ullah , Shah Syed Bilal Hussain , Wang Lei , Aziz Muhammad Adnan , Stephan Thompson , Kumar Neeraj 
Published: June 2021

SummaryNowadays, as the world is transformed because of the interconnectivity, there we see several issues regarding security which is supposed to be one of the biggest problems for the concept of smart cities. In future, aerial vehicles can be merged with smart cities to enhance the interoperability among internet of things (IoT) devices. Routing protocols plays an important role when flying vehicles communicate with one another. Reinforcing connection in flying ad hoc networks using routing protocols is the optimal way to reduce end‐to‐end delay. However, utilizing flying networks with the deployment of routing techniques is a very difficult task to tackle the dynamic pattern of aerial vehicles. Internet of flying vehicles is the emerging area which is still in the evolutionary process; however, the interconnectivity can be efficiently formulated by applying security algorithms for improving signal power. In unmanned aerial vehicles (UAVs), every node will have some specific location, direction, speed, velocity, and acceleration which will identify and relate information about mobility model. This paper proposes a novel routing technique, which is the extension of AntHocNet due to mobile characteristics; it is termed as flying nature inspired algorithm. Also a case study is conducted to improve the signal power using modeled learning approach called decision tree. Experimental simulations are managed on network simulators that prove the proposed work efficiency.
A profile of brain reserve in adults at genetic risk of Alzheimer's disease
Authors: Coughlan Gillian , Zhukovsky Peter , Voineskos Aristotle , Grady Cheryl 
Published: June 2021

AbstractIntroductionThe apolipoprotein E (APOE) ε4 allele is the greatest genetic risk factor for Alzheimer's disease (AD). Our aim was to identify the structural brain measures that mitigate the negative effect of APOE ε4 on cognition, which would have implications for AD diagnosis and treatment trial selection.MethodsA total of 742 older adults (mean age: 70.1 ± 8.7 years) were stratified by APOE status and classified as cognitively normal (CDR 0) or with very mild dementia (CDR 0.5). Regional brain volume and cognitive performance were measured.ResultsThere were significant interactions between APOE and CDR on the left precuneus and on bilateral superior frontal volumes. These regions were preserved in CDR‐0 ε3/ε4 and ε4/ε4 carriers but were reduced in CDR‐0.5 ε3/ε4 and ε4/ε4 carriers, compared to their respective ε3/ε3 counterparts. Educational attainment predicted greater brain reserve.DiscussionThis pattern of preserved brain structure in cognitively normal ε4 carriers with comprised medial temporal volume is consistent with the theory of brain reserve.
Management‐mediated predation rate in the caribou–moose–wolf system: spatial configuration of logging activities matters
Authors: Vanlandeghem Virginie , Drapeau Pierre , Prima Marie‐Caroline , St‐Laurent Martin‐Hugues , Fortin Daniel 
Published: June 2021

AbstractLandscape complexity can determine the population dynamics of interacting predators and prey. Yet, management plans are commonly developed from aspatial predictive models. This oversight may result in unexpected outcomes or the loss of opportunities to make spatial interventions that would increase a plan's effectiveness. The management of the threatened woodland caribou (Rangifer tarandus caribou), boreal population, provides an example of such shortcomings when using an aspatial approach. Currently, the most influential management recommendation is to maintain at least 65% of undisturbed forests in areas occupied by caribou populations, regardless of the spatial configuration of the forest cover. Using a spatially explicit individual‐based model (IBM), we evaluated the effects of the spatial configuration of cuts and roads on the mortality of boreal caribou living in sympatry with wolves (Canis lupus) and moose (Alces alces), an apparent competitor. Starting with a real forest landscape, we created forest management scenarios of the specific spatial distribution of cuts (mosaic, small, or large agglomeration) with increasing disturbance levels. We then ran the IBM with simulated agents, representing individuals of the three species, moving according to movement rules determined from radio‐collared individuals. We found that movement responses to land cover types and roads differed among species. For example, caribou and moose generally avoided areas close to roads, contrary to wolves. Those differences influenced the mortality of caribou agents, which not only depended on the levels of disturbance but also depended on the spatial distribution of cuts and roads. After controlling for disturbance level, wolves were more successful when forest management required an extensive road network resulting in relatively high habitat fragmentation. Caribou agents experienced lower mortality in landscapes with low densities of road and disturbance‐related edges. The effect remained much stronger, however, for the level than the spatial configuration of human disturbances. Still, our IBM demonstrated how landscape management could be used to manipulate species interactions, with the intent of either increasing or decreasing predation rates on specific populations, depending on management goals.
Proactive inhibition is not modified by deep brain stimulation for Parkinson's disease: An electrical neuroimaging study
Authors: De Pretto Michael , Mouthon Michael , Debove Ines , Pollo Claudio , Schüpbach Michael , Spierer Lucas , Accolla Ettore A. 
Published: June 2021

AbstractIn predictable contexts, motor inhibitory control can be deployed before the actual need for response suppression. The brain functional underpinnings of proactive inhibition, and notably the role of basal ganglia, are not entirely identified. We investigated the effects of deep brain stimulation of the subthalamic nucleus or internal globus pallidus on proactive inhibition in patients with Parkinson's disease. They completed a cued go/no‐go proactive inhibition task ON and (unilateral) OFF stimulation while EEG was recorded. We found no behavioural effect of either subthalamic nucleus or internal globus pallidus deep brain stimulation on proactive inhibition, despite a general improvement of motor performance with subthalamic nucleus stimulation. In the non‐operated and subthalamic nucleus group, we identified periods of topographic EEG modulation by the level of proactive inhibition. In the subthalamic nucleus group, source estimation analysis suggested the initial involvement of bilateral frontal and occipital areas, followed by a right lateralized fronto‐basal network, and finally of right premotor and left parietal regions. Our results confirm the overall preservation of proactive inhibition capacities in both subthalamic nucleus and internal globus pallidus deep brain stimulation, and suggest a partly segregated network for proactive inhibition, with a preferential recruitment of the indirect pathway.
Hypoxia‐Inducible Exosomes Facilitate Liver‐Tropic Premetastatic Niche in Colorectal Cancer
Authors: Sun Hao , Meng Qingtao , Shi Chengyu , Yang Hongbao , Li Xiaobo , Wu Shenshen , Familiari Giuseppe , Relucenti Michela , Aschner Michael , Wang Xuehao , Chen Rui 
Published: June 2021

Background and Aims
Liver metastasis is a frequent occurrence in patients with colorectal cancer (CRC), with 15%‐25% of CRC patients having liver metastases at the time of initial diagnosis. Specifically, some regional‐stage patients with mild symptoms (stage 1 or 2) will also advance to liver metastases rapidly, even if the CRC lesion in situ is resected in time. Nevertheless, the precise mechanism of liver metastasis is still unclear.

Approach and Results
Fresh tumor tissues from patients with CRC, adjacent noncancerous tissues, and colorectal adenoma tissues were subjected to microarray analysis to identify differentially expressed microRNA. Exosomes from human serum and cell culture medium were separated, quantitated, and verified by transmission electronic microscopy and Zetasizer Nano. Luciferase reporter assay, real‐time quantitative PCR, western blot, immunoprecipitation, chromatin and re‐chromatin immunoprecipitation, migration and invasion assay, PDX mouse model, flow cytometry, immunohistochemistry, and immunofluorescence staining were employed to explore the regulation among CRC liver metastases, immunosuppression, and cell adhesion. In this study, we demonstrated that the hypoxic microenvironment in primary CRC lesions boosted exosome release, selectively initiated favorable premetastatic niche formation in the liver but not in other organs. Mechanistically, Kupffer cells (KCs) can phagocytose exosomes containing highly expressed miR‐135a‐5p from the blood circulation into the liver. Exosomal miR‐135a‐5p initiated the large tumor suppressor kinase 2–yes‐associated protein–matrix metalloproteinase 7 axis to promote the occurrence of CRC liver metastasis, and cluster of differentiation 30–TNF receptor–associated factor 2–p65–mediated immunosuppression signaling also contributed to this process.

Conclusions
Hypoxia‐induced exosomal miR‐135a‐5p correlates with the development, clinical severity, and prognosis of CRC liver metastases through the premetastatic niche; and our findings revealed that miR‐135a‐5p might be a promising target in halting CRC liver metastases.
Exploratory composite endpoint demonstrates benefit of trilaciclib across multiple clinically meaningful components of myeloprotection in patients with small cell lung cancer
Authors: Dómine Gómez Manuel , Csőszi Tibor , Jaal Jana , Kudaba Iveta , Nikolov Krasimir , Radosavljevic Davorin , Xiao Jie , Horton Janet K. , Malik Rajesh K. , Subramanian Janakiraman 
Published: June 2021

AbstractChemotherapy‐induced myelosuppression is an acute, dose‐limiting toxicity of chemotherapy regimens used in the treatment of extensive‐stage small cell lung cancer (ES‐SCLC). Trilaciclib protects haematopoietic stem and progenitor cells from chemotherapy‐induced damage (myeloprotection). To assess the totality of the myeloprotective benefits of trilaciclib, including analysis of several clinically relevant but low‐frequency events, an exploratory composite endpoint comprising five major adverse haematological events (MAHE) was prospectively defined: all‐cause hospitalisations, all‐cause chemotherapy dose reductions, febrile neutropenia (FN), prolonged severe neutropenia (SN) and red blood cell (RBC) transfusions on/after Week 5. MAHE and its individual components were assessed in three randomised, double‐blind, placebo‐controlled Phase 2 trials in patients receiving a platinum/etoposide or topotecan‐containing chemotherapy regimen for ES‐SCLC and in data pooled from the three trials. A total of 242 patients were randomised across the three trials (trilaciclib, n = 123; placebo, n = 119). In the individual trials and the pooled analysis, administering trilaciclib prior to chemotherapy resulted in a statistically significant reduction in the cumulative incidence of MAHE compared to placebo. In the pooled analysis, the cumulative incidences of all‐cause chemotherapy dose reductions, FN, prolonged SN and RBC transfusions on/after Week 5 were significantly reduced with trilaciclib vs placebo; however, no significant difference was observed in rates of all‐cause hospitalisations. Additionally, compared to placebo, trilaciclib significantly extended the amount of time patients remained free of MAHE. These data support the myeloprotective benefits of trilaciclib and its ability to improve the overall safety profile of myelosuppressive chemotherapy regimens used to treat patients with ES‐SCLC.
Phase I clinical trial of HC‐1119: A deuterated form of enzalutamide
Authors: Li Xiaoyu , Cheng Ke , Li Xinghai , Zhou Yuwen , Liu Jiyan , Zeng Hao , Chen Yuanwei , Liu Xiao , Zhang Ying , Wang Yongsheng , Bi Feng , Zheng Li 
Published: June 2021

AbstractThe purpose of our study was to investigate the safety, pharmacokinetics (PK), and initial antitumor efficacy of HC‐1119 in patients with metastatic castration‐resistant prostate cancer (mCRPC). Eligible mCRPC patients were included in our study (NCT 03774056) with two parts. Part A was a dose escalation study in which patients received a dose escalation of HC‐1119 (40, 80, 160 and 200 mg/day). Part B was a dose expansion study in which patients received HC‐1119 at the dose of 80 and 160 mg. Safety assessment and pharmacokinetic samplings were performed for all patients at the given time points; preliminary tumor response was also assessed. Twenty‐four patients were enrolled in part A and 19 patients in part B, respectively. HC‐1119 was safe, well tolerated and no dose‐limiting toxicity was observed. Fatigue was the most common treatment‐related adverse event and no seizures were observed. At the dose levels of 40, 80 and 160 mg, the AUC and Cmax of HC‐1119 in plasma increased almost dose‐proportionally at the steady state in mCRPC patients. Maximum prostate‐specific antigen (PSA) response rates (≥50% reduction from the baseline) in dose escalation and dose expansion cohorts were 77% and 75%, respectively; the overall disease control rate (22 patients available for imaging analysis) was 72.7%, with PR in 4 patients, SD in 12 patients and PD in 6 patients; the 2‐year overall survival rate in patients from Part B was 56.8%. HC‐1119 was safe, well tolerated and efficacious and HC‐1119 at 80 mg/day is recommended for further studies.
Mass spectrometry‐based urinary metabolomics for exploring the treatment effects of Radix ginseng‐Schisandra chinensis herb pair on Alzheimer's disease in rats
Authors: Wang Aimin , Pi Zifeng , Liu Shu , Zheng Zhong , Liu Zhiqiang , Song Fengrui 
Published: June 2021

AbstractHerb pairs are the unique combinations of two relatively fixed herbs, intrinsically convey the basic idea of traditional Chinese medicine prescriptions. The compatibility of Radix ginseng and Schisandra chinensis has been used in traditional Chinese medicine for treating Alzheimer's disease for many years. However, there are few studies on Radix ginseng‐Schisandra chinensis herb pair, and the underlying action mechanism is still unclear. In this study, the mechanism of Radix ginseng‐Schisandra chinensis herb pair on Alzheimer's disease was investigated by using the mass spectrometry‐based urinary metabolomics method. Sixteen urinary endogenous metabolites were identified as potential biomarkers. Meanwhile, 10 biomarkers were quantified with tandem mass spectrometry. The study result showed that the brain pathologic symptoms of model rats were improved and the potential biomarkers were adjusted backward significantly after the herb pair administration. The metabolic pathways linked to the herb pair‐regulated endogenous biomarkers included phenylalanine and tyrosine metabolism, tryptophan metabolism, purine metabolism, and so on. The above metabolic pathways reflected that Radix ginseng‐Schisandra chinensis herb pair mainly regulates abnormal energy metabolism, reduces inflammation, and regulates gut microbiota and neurotransmitters in the treatment of Alzheimer's disease.
Recent developments in Lablab purpureus genomics: A focus on drought stress tolerance and use of genomic resources to develop stress‐resilient varieties
Authors: Missanga Julius S. , Venkataramana Pavithravani B. , Ndakidemi Patrick A. 
Published: June 2021

AbstractDrought is a major climatic challenge that contributes significantly to the decline of food productivity. One of the strategies to overcome this challenge is the use of drought‐tolerant crops with a wide range of benefits. Lablab is a leguminous crop that has been showing high promise to drought tolerance. It is reported to have higher drought resilience compared with the commonly cultivated legumes such as common beans and cowpeas. Because of its great genetic diversity, Lablab can withstand high temperature and low rainfall, unlike other related crops. On top of that, it is grown for multitudes of purposes including food, forages, conservation agriculture, and improved soil fertility. To enhance its production and benefits during the present effects of climate change, it is crucial to develop improved varieties that would overcome the challenge of drought stress. In the past years, there have been several reviews on Lablab based on origin, domestication, characterization, utilization, germplasm conservation, some cultivation constraints, and conventional breeding with limitations on the genomic exploitation of the crop for drought tolerance. Conventional breeding is the major breeding technique for many Lablab cultivars. The integration of genomic, physiological, biochemical, and molecular approaches would be required to develop drought‐tolerant cultivars of Lablab. In this review, we discuss recent developments in Lablab genomics with a focus on drought stress tolerance and the use of genomic resources to develop stress‐resilient varieties.
An efficient climate index for reflecting cooling energy consumption: Cooling degree days based on wet bulb temperature
Authors: Cao Jingfu , Li Mingcai , Zhang Ruixue , Wang Min 
Published: June 2021

AbstractCooling energy consumption of buildings is not only used for decreasing temperature, but for dehumidification. Therefore, cooling degree day (CDD) based on only temperature is insufficient for estimating the cooling energy consumption in buildings. In the present study, we aim to propose an efficient climate index (i.e., CDD based on wet bulb temperature [WBT], WCDD) based on the combination of cooling energy consumption in a building and joint probability of temperature and humidity. In addition, the adaptation of the new WCDD was verified in 14 cities of different climate zones in China. The results showed that CDD based on dry bulb temperature (DBT) (DCDD) can only explain 17%–60% of cooling energy consumption, whereas WCDD explaining 86%–97% of cooling energy consumption in the different climate zones. The optimal base WBTs are generally 17.74, 19.44, 21.04 and 22.56°C for the four climate zones, respectively. The present study reveals that WCDD by combining effects of temperature and humidity on cooling energy consumption can be much more efficiently used to estimate the cooling energy consumption compared with DCDD. More importantly, the WCDD is suitable for reflecting the cooling energy consumption for different climate zones. The collaborative changes of temperature and humidity under the conditions of climate change should be fully considered to take measures for decreasing the energy consumption for decreasing temperature and dehumidification.
Fast reliability ranking of matchstick minimal networks
Authors: Drǎgoi Vlad‐Florin , Beiu Valeriu 
Published: June 2021

AbstractIn this article, we take a closer look at the reliability of large minimal networks constructed by repeated compositions of the simplest possible networks. For a given number of devices we define the set of all the possible compositions of series and parallel networks of two devices. We then define several partial orders over this set and study their properties. As far as we know the ranking problem has not been addressed before in this context, and this article establishes the first results in this direction. The usual approach when dealing with reliability of two‐terminal networks is to determine existence or nonexistence of uniformly most reliable networks. The problem of ranking two‐terminal networks is thus more complex, but by restricting our study to the set of compositions we manage to determine and demonstrate the existence of at least a graded poset.
Sarcoidosis of the mandibular condyle manifesting as a temporomandibular joint arthrosis: A rare case report
Authors: Hori (Wakao) Sayaka , Tomihara Kei , Sekido Katsuhisa , Tachinami Hidetake , Imaue Shuichi , Fujiwara Kumiko , Noguchi Makoto 
Published: June 2021

AbstractBone sarcoidosis is uncommon, and involvement of the temporomandibular joint is exceptionally rare. We report an unusual case of mandibular condyle sarcoidosis in a 51‐year‐old Japanese woman that manifested as a temporomandibular joint arthritis. The patient was referred for a chief complaint of a painful temporomandibular joint and was initially diagnosed with temporomandibular joint arthritis. However, a more detailed examination revealed bone sarcoidosis in the mandibular condyle and the progression of preexisting cardiac sarcoidosis. Oral steroid treatment (tapered from 50 mg/day to 5 mg/day) appears to have been successful over a 1‐year follow‐up.