bluuebunny/crossref_metadata_2025_split huggingface dataset:
Types of cancer and outcomes in patients with cancer requiring admission from the emergency department: A nationwide, population‐based study, 2016‐2017
Authors: Kim Youn‐Jung , Seo Dong‐Woo , Kim Won Young 
Published: March 2021

BACKGROUNDEmergency department (ED) utilization and emergency admissions by patients with cancer have increased. The authors aimed to evaluate the characteristics of patients with cancer admitted through the ED and determine whether cancer types are related to in‐hospital mortality.METHODSThe National Emergency Department Information System database of patients visiting EDs in South Korea between 2016 and 2017 was analyzed. Among 6,179,088 adult patients who presented to an ED with nontraumatic medical illness, patients with cancer were identified. The primary outcome was in‐hospital mortality.RESULTSPatients with cancer accounted for 6.8% of ED visits, and 239,630 patients (57.0%) were admitted to the hospital (intensive care unit [ICU], 9.5%; others, 90.5%). The prevalent cancers requiring hospitalization were lung cancer (15.7%), liver cancer (14.2%), and colon cancer (11.6%). The commonest reasons for admission other than cancer‐related medical problems (41.4%) were pneumonia (4.8%) and hepatobiliary infection (2.8%). Overall in‐hospital mortality was 16.1% (ICU, 28.3%; general wards, 14.8%); lung cancer (22.9%), liver cancer (19.7%), and leukemia/multiple myeloma (17.8%) showed the highest mortality rates. The highest odds for mortality were for lung cancer (adjusted odds ratio [OR], 2.227; 95% confidence interval [CI], 2.124‐2.335; P < .001) and liver cancer (adjusted OR, 1.839; 95% CI, 1.751‐1.930; P < .001), which were referenced to genitourinary cancer by multivariable logistic regression analysis.CONCLUSIONSMore than half of the patients with cancer visiting EDs were admitted to the hospital with a mortality rate of 16.1%. Physicians treating patients with cancer and policymakers and planners designing health systems should understand the different prevalences and outcomes of oncological emergencies by cancer type to improve patient care.
The application of corporate social responsibility (CSR) actions for mitigation of environmental, social, corporate governance (ESG) and reputational risk in integrated reports
Authors: Karwowski Mariusz , Raulinajtys‐Grzybek Monika 
Published: March 2021

AbstractMany studies stress the importance of understanding actions within sustainable development to prevent risks brought by companies. Environment, social factors, corporate governance (ESG) as well as reputation are even more important risk factors. In turn, companies can take corporate social responsibility (CSR) actions to avoid ESG and reputational risk. The aim of the article is to analyze the role of CSR in risk mitigation. The study includes content analysis of integrated reports in terms of reporting information on both risk and CSR activities such as stakeholder engagement or environmental policy. The companies most often indicate governmental risk, followed by social risk. The most common CSR actions are those related to social impact. Despite the fact that the analyzed database of over 120 integrated reports is not fully homogeneous, the conducted research shows a statistically important correlation in categorization of risks and CSR actions. Both statistical analysis and analysis of the content of reports confirms that companies identify their ESG and reputational risks and use CSR actions to mitigate them.
Degradation of Carbon Electrodes in the All‐Vanadium Redox Flow Battery
Authors: Singh Ashutosh K. , Pahlevaninezhad Maedeh , Yasri Nael , Roberts Edward P. L. 
Published: March 2021

AbstractThe charge−discharge operation of the vanadium redox flow battery degrades the electrodes over time and results in a performance and efficiency decay. The impact of extended charge−discharge cycling operation on carbon electrodes is investigated using carbon paper as a model electrode. Electrode degradation along with 70 % degradation of charge−discharge capacity was observed after 100 charge−discharge cycles of a single cell vanadium redox flow battery operating at a current density of 80 mA cm−2 at room temperature (23 °C). Raman mapping of the electrodes shows a decrease in structural defects in the negative electrode, and an increase in defects in the positive electrode, indicating differences in the degradation mechanism at each electrode. Electrochemical investigation reveals an increase in the activation overpotential at both the positive and negative electrodes. However, the negative electrode showed a higher activation overpotential indicating a higher impact of electrode degradation on the negative side. X‐ray photoelectron spectroscopy shows around an eightfold increase in surface oxygen functional groups after degradation in both positive and negative electrodes. The composition of oxygen functional groups was also observed to change significantly after degradation from dominantly carbonyl‐based to a combination of carbonyl‐ and carboxyl‐based groups. This study provides insight into the electrode degradation mechanism and highlights the differences in the mechanism for the positive and negative electrodes.
A fast settling frequency synthesizer with switched‐bandwidth loop filter
Authors: Beiraghdar Farhad , Ghobadi Rad Alireza , Sheikhaei Samad , Tohidian Massoud 
Published: March 2021

SummaryThis paper presents a new method to substantially decrease the settling time of analog phase‐locked loops (PLLs) while keeping its phase noise unaffected. This is achieved by switching the loop filter capacitors and resistor in such a way that output frequency is kept seamless. This method only affects the loop filter architecture and does not need any other changes to other blocks of the PLL. A frequency synthesizer circuit is implemented to validate the proposed method. The reference synthesizer has a 342‐μs settling time for a 1‐GHz frequency step (1.5 to 2.5 GHz), while if the proposed technique is enabled, the settling time is reduced to 48 μs (worst case). The measured phase noise of the synthesizer at 10‐kHz offset from a 2‐GHz carrier is −110 dBc/Hz.
Immature reticulocytes are sensitive and specific to low‐dose erythropoietin treatment at sea level and altitude
Authors: Jeppesen Jan Sommer , Breenfeldt Andersen Andreas , Bonne Thomas Christian , Thomassen Martin , Sørensen Helle , Nordsborg Nikolai Baastrup , Olsen Niels Vidiendal , Huertas Jesús Rodríguez , Bejder Jacob 
Published: March 2021

AbstractWe investigated whether immature reticulocyte fraction (IRF) and immature reticulocytes to red blood cells ratio (IR/RBC) are sensitive biomarkers for low‐dose recombinant human erythropoietin (rhEpo) treatment at sea level (SL) and moderate altitude (AL) and whether multi (FACS) or single (Sysmex‐XN) fluorescence flow cytometry is superior for IRF and IR/RBC determination. Thirty‐nine participants completed two interventions, each containing a 4‐week baseline, a 4‐week SL or AL (2,230 m) exposure, and a 4‐week follow‐up. During exposure, rhEpo (20 IU kg−1) or placebo (PLA) was injected at SL (SLrhEpo, n = 25, SLPLA n = 9) and AL (ALrhEpo, n = 12, ALPLA n = 27) every second day for 3 weeks. Venous blood was collected weekly. Sysmex measurements revealed that IRF and IR/RBC were up to ~70% (P < 0.01) and ~190% (P < 0.001) higher in SLrhEpo than SLPLA during treatment and up to ~45% (P < 0.001) and ~55% (P < 0.01) lower post‐treatment, respectively. Compared with ALPLA, IRF and IR/RBC were up to ~20% (P < 0.05) and ~45% (P < 0.001) lower post‐treatment in SLrhEpo, respectively. In ALrhEpo, IRF and IR/RBC were up to ~40% (P < 0.05) and ~110% (P < 0.001) higher during treatment and up to ~25% (P < 0.05) and ~40% (P < 0.05) lower post‐treatment, respectively, compared with ALPLA. Calculated thresholds provided ~90% sensitivity for both biomarkers at SL and 33% (IRF) and 66% (IR/RBC) at AL. Specificity was >99%. Single‐fluorescence flow cytometry coefficient of variation was >twofold higher at baseline (P < 0.001) and provided larger or similar changes compared to multi‐fluorescence, albeit with smaller precision. In conclusion, IRF and IR/RBC were sensitive and specific biomarkers for low‐dose rhEpo misuse at SL and AL.
Impact of Phytophthora agathidicida infection on canopy and forest floor plant nutrient concentrations and fluxes in a kauri‐dominated forest
Authors: Schwendenmann Luitgard , Michalzik Beate 
Published: March 2021

AbstractKauri dieback, caused by Phytophthora agathidicida, is a biotic disturbance that poses a recent threat to the survival of kauri (Agathis australis) forests in New Zealand. Previous studies have shown that throughfall and stemflow play an important role in the kauri forests’ internal nutrient cycle. However, the effects of P. agathidicida infection on canopy and forest floor nutrient fluxes in kauri forests remain unknown. Here, we measured throughfall, stemflow and forest floor water yield, nutrient (potassium, calcium, magnesium, manganese, silicon, sulfur, sodium, iron) concentrations and fluxes of ten kauri trees differing in soil P. agathidicida DNA concentration, and health status. We did not observe an effect of soil P. agathidicida DNA concentration on throughfall, stemflow, and forest floor water yield. Throughfall and forest floor nutrient concentrations and fluxes decreased (up to 50%) with increasing soil P. agathidicida DNA concentration. We found significant effects on potassium and manganese fluxes in throughfall; calcium and silicon fluxes in forest floor leachate. A decline in canopy and forest floor nutrient fluxes may result in soil nutrient imbalances, which in turn may negatively impact forest productivity and may increase the susceptibility of trees to future pathogen infection in these ecologically unique kauri forests. Given our findings and the increasing spread of Phytophthora species worldwide, research on the underlying physiological mechanisms linking dieback and plant–soil nutrient fluxes is critical.
Cyclometallated 2‐Phenylpyrimidine Derived Platinum Complexes: Synthesis and Photophysical Properties
Authors: Fecková Michaela , Kahlal Samia , Roisnel Thierry , Saillard Jean‐Yves , Boixel Julien , Hruzd Mariia , le Poul Pascal , Gauthier Sébastien , Robin‐le Guen Françoise , Bureš Filip , Achelle Sylvain 
Published: March 2021

AbstractA series of five platinum (II) complexes based on 2‐phenylpyrimidine ligands have been designed. Pyridine and chloride were used as auxiliary ligands. These complexes exhibit a slightly distorted square‐planar geometry. The nature and position of substituent on the phenyl ring was thoroughly studied. The presence of an electron‐donating substituent on the phenyl ring in the para position of the platinum atom leads to a red shift of the lowest‐energy absorption band, which corresponds to the HOMO→LUMO transition and permits to obtain phosphorescence in deoxygenated CH2Cl2 solution. All compounds are emissive in the solid state with a significant redshift for complexes bearing electron‐donating substituent on the phenyl ring of phenylpyrimidine ligand.
Maleic Acid/Thiourea‐Catalyzed Dearomative ipso‐Friedel–Crafts Reaction of Indoles to Produce Functionalized Spiroindolenines
Authors: Ueda Jun , Harada Shingo , Kobayashi Mayu , Yanagawa Mai , Nemoto Tetsuhiro 
Published: March 2021

AbstractA dearomative spirocyclization of diazo‐functionalized indoles was developed under metal‐free conditions. Although the spiroindolenine architecture with a tertiary alkyl substituent at the 2‐position is a privileged scaffold of bioactive molecules, a general synthetic strategy has remained elusive. In this study, a dual catalyst system comprising maleic acid and Schreiner's thiourea was used to construct a spiroindolenine core that was inaccessible by rhodium or silver catalysis. Computational studies revealed a unique macrocyclic transition state consisting of the substrate, maleic acid, and thiourea cocatalyst, which lowered the activation energy of spirocyclization through multipoint mutual interactions.
Abnormal sensory thresholds of dystonic patients are not affected by deep brain stimulation
Authors: Listik Clarice , Cury Rubens Gisbert , da Silva Valquiria Aparecida , Casagrande Sara Carvalho Barbosa , Listik Eduardo , Link Naira , Galhardoni Ricardo , Barbosa Egberto Reis , Teixeira Manoel Jacobsen , Ciampi de Andrade Daniel 
Published: March 2021

AbstractBackgroundUnlike motor symptoms, the effects of deep brain stimulation (DBS) on non‐motor symptoms associated with dystonia remain unknown.MethodsThe objective of this study was to assess the effects of DBS on evoked experimental pain and cutaneous sensory thresholds in a crossover, double‐blind on/off study and compare these results with those of healthy volunteers (HV).ResultsSixteen patients with idiopathic dystonia (39.9 ± 13 years old, n = 14 generalized) with DBS of the globus pallidus internus underwent a battery of quantitative sensory testing and assessment using a pain top‐down modulation system (conditioned pain modulation, CPM). Results for the more and less dystonic body regions were compared in on and off stimulation. The patients' results were compared to age‐ and sex‐matched HV. Descending pain modulation CPM responses in dystonic patients (on‐DBS, 11.8 ± 40.7; off‐DBS, 1.8 ± 22.1) was abnormally low (defective) compared to HV (−15.6 ± 23.5, respectively p = .006 and p = .042). Cold pain threshold and cold hyperalgesia were 54.8% and 95.7% higher in dystonic patients compared to HV. On‐DBS CPM correlated with higher Burke‐Fahn‐Marsden disability score (r = 0.598; p = .014). While sensory and pain thresholds were not affected by DBS on/off condition, pain modulation was abnormal in dystonic patients and tended to be aggravated by DBS.ConclusionThe analgesic effects after DBS do not seem to depend on short‐duration changes in cutaneous sensory thresholds in dystonic patients and may be related to changes in the central processing of nociceptive inputs.
ProBDNF induces sustained elevation of intracellular Ca2+ possibly mediated by TRPM7 channels in rodent microglial cells
Authors: Mizoguchi Yoshito , Ohgidani Masahiro , Haraguchi Yoshinori , Murakawa‐Hirachi Toru , Kato Takahiro A. , Monji Akira 
Published: March 2021

AbstractMicroglia are intrinsic immune cells that release factors including pro‐ and anti‐inflammatory cytokines, nitric oxide (NO) and neurotrophins following activation in the brain. Elevation of intracellular Ca2+ concentration ([Ca2+]i) is important for microglial functions, such as the release of cytokines or NO from activated microglia. Brain‐derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia. Interestingly, proBDNF, the precursor form of mature BDNF, and mature BDNF elicit opposing neuronal responses in the brain. Mature BDNF induces sustained intracellular Ca2+ elevation through the upregulation of the surface expression of TRPC3 channels in rodent microglial cells. In addition, TRPC3 channels are important for the BDNF‐induced suppression of NO production in activated microglia. In this study, we observed that proBDNF and mature BDNF have opposite effects on the relative expression of surface p75 neurotrophin receptor (p75NTR) in rodent microglial cells. ProBDNF induces a sustained elevation of [Ca2+]i through binding to the p75NTR, which is possibly mediated by Rac 1 activation and TRPM7 channels in rodent microglial cells. Flow cytometry showed that proBDNF increased the relative surface expression of TRPM7. Although proBDNF did not affect either mRNA expression of pro‐ and anti‐inflammatory cytokines or the phagocytic activity, proBDNF potentiates the generation of NO induced by IFN‐γ and TRPM7 channels could be involved in the proBDNF‐induced potentiation of IFN‐γ‐mediated production of NO. We show direct evidence that rodent microglial cells are able to respond to proBDNF, which might be important for the regulation of inflammatory responses in the brain.
Spatial correlation maps of the hippocampus with cerebrospinal fluid biomarkers and cognition in Alzheimer's disease: A longitudinal study
Authors: Liu Guodong , Liu Chaoqiang , Qiu Anqi ,   the Alzheimer's Disease Neuroimaging Initiative
Published: March 2021

AbstractThis study is an observational study that takes the existing longitudinal data from Alzheimer's disease Neuroimaging Initiative to examine the spatial correlation map of hippocampal subfield atrophy with CSF biomarkers and cognitive decline in the course of AD. This study included 421 healthy controls (HC), 557 patients of stable mild cognitive impairment (s‐MCI), 304 Alzheimer's Disease (AD) patients, and 241 subjects who converted to be AD from MCI (c‐MCI), and 6,525 MRI scans in a period from 2004 to 2019. Our findings revealed that all the hippocampal subfields showed their accelerated atrophy rate from cognitively normal aging to stable MCI and AD. The presubiculum, dentate gyrus, and fimbria showed greater atrophy beyond the whole hippocampus in the HC, s‐MCI, and AD groups and corresponded to a greater decline of memory and attention in the s‐MCI group. Moreover, the higher atrophy rates of the subiculum and CA2/3, CA4 were also associated with a greater decline in attention in the s‐MCI group. Interestingly, patients with c‐MCI showed that the presubiculum atrophy was associated with CSF tau levels and corresponded to the onset age of AD and a decline in attention in patients with c‐MCI. These spatial correlation findings of the hippocampus suggested that the hippocampal subfields may not be equally impacted by normal aging, MCI, and AD, and their atrophy was selectively associated with declines in specific cognitive domains. The presubiculum atrophy was highlighted as a surrogate marker for the AD prognosis along with tau pathology and attention decline.
Analysis and Validation of Human Targets and Treatments Using a Hepatocellular Carcinoma–Immune Humanized Mouse Model
Authors: Zhao Yue , Wang Jiaxu , Liu Wai Nam , Fong Shin Yie , Shuen Timothy Wai Ho , Liu Min , Harden Sarah , Tan Sue Yee , Cheng Jia Ying , Tan Wilson Wei Sheng , Chan Jerry Kok Yen , Chee Cheng Ean , Lee Guan Huei , Toh Han Chong , Lim Seng Gee , Wan Yue , Chen Qingfeng 
Published: March 2021

Background and Aims
Recent development of multiple treatments for human hepatocellular carcinoma (HCC) has allowed for the selection of combination therapy to enhance the effectiveness of monotherapy. Optimal selection of therapies is based on both HCC and its microenvironment. Therefore, it is critical to develop and validate preclinical animal models for testing clinical therapeutic solutions.

Approach and Results
We established cell line–based or patient‐derived xenograft–based humanized‐immune‐system mouse models with subcutaneous and orthotopic HCC. Mice were injected with human‐specific antibodies (Abs) to deplete human immune cells. We analyzed the transcription profiles of HCC cells and human immune cells by using real‐time PCR and RNA sequencing. The protein level of HCC tumor cells/tissues or human immune cells was determined by using flow cytometry, western blotting, and immunohistochemistry. The HCC tumor size was measured after single, dual‐combination, and triple‐combination treatment using N‐(1ʹ,2‐Dihydroxy‐1,2ʹ‐binaphthalen‐4ʹ‐yl)‐4‐methoxybenzenesulfonamide (C188‐9), bevacizumab, and pembrolizumab. In this study, human immune cells in the tumor microenvironment were strongly selected and modulated by HCC, which promoted the activation of the IL‐6/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in tumor cells and led to augmented HCC proliferation and angiogenesis by releasing angiogenic cytokines in humanized‐immune‐system mice with HCC. In particular, intratumor human cluster of differentiation–positive (hCD14+) cells could produce IL‐33 through damage‐associated molecular pattern/Toll‐like receptor 4/activator protein 1, which up‐regulated IL‐6 in other intratumor immune cells and activated the JAK2/STAT3 pathway in HCC. Specific knockdown of the CD14 gene in human monocytes could impair IL‐33 production induced by cell lysates. Subsequently, we evaluated the in vivo anti‐HCC effect of C188‐9, bevacizumab, and pembrolizumab. The results showed that the anti‐HCC effect of triple‐combination therapy was superior to that of single or dual treatments.

Conclusions
Humanized‐immune‐system HCC mouse models are suitable for identifying targets from cancer and immune components and for testing combinational therapies.
Synthesis of Highly Substituted Cyclobutanones by a One‐Pot Keteniminium‐Enamine Process
Authors: Dagoneau Dylan , Kolleth Amandine , Quinodoz Pierre , Horoz Beyza , Catak Saron , Lumbroso Alexandre , Sulzer‐Mossé Sarah , De Mesmaeker Alain 
Published: March 2021

AbstractHerein, we describe an effective one‐pot sequence for the regio‐ and stereoselective synthesis of highly substituted cyclobutanones. This process relies on first a [2+2] cycloaddition involving a keteniminium salt intermediate with an alkene followed by isomerization of the resulting cyclobutaniminium salt into its cyclic enamine form and then reaction of the latter with an electrophile. The adduct can be either hydrolyzed or reduced to give the corresponding cyclobutanone or cyclobutanamine, respectively, with excellent diastereocontrol. A variety of electrophiles was tolerated allowing the incorporation of diverse substituents and functionalities onto the cyclobutyl ring. Additionally, the coplanarity of diverse cyclic enamines was investigated through a DFT study.
Outcomes of patients with intermediate‐risk or poor‐risk metastatic renal cell carcinoma who received their first cycle of nivolumab and ipilimumab in the hospital because of symptomatic disease: The MD Anderson Cancer Center experience
Authors: Alhalabi Omar , Hasanov Elshad , Wilson Nathaniel R. , Araujo John , Wang Jianbo , Campbell Matthew T. , Goswami Sangeeta , Shah Amishi Y. , Gao Jianjun , Msaouel Pavlos , Tannir Nizar M. 
Published: March 2021

AbstractNivolumab plus ipilimumab (nivo/ipi) is an approved therapy for patients with intermediate‐risk or poor‐risk metastatic renal cell carcinoma (mRCC). Clinical factors that guide the selection of this regimen for patients with mRCC are urgently needed. We retrospectively analyzed medical records of patients with mRCC who were hospitalized at MD Anderson Cancer Center because of cancer‐related symptoms and received their first cycle of nivo/ipi in the inpatient setting. Clinical parameters, including demographics, histology, clinical history, response, and survival, were collected. The 4‐month survival probability, progression‐free survival (PFS), and overall survival (OS) were calculated using Kaplan‐Meier methods. Between November 2017 and 21 June 2020 patients were identified that fit the search: 19 patients (91%) had poor‐risk disease based on the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score; 17 patients (81%) had ≥4 risk factors; and 9 patients (43%) had sarcomatoid features on histology. Shortness of breath (28%) and abdominal pain (19%) were the two most common reasons for hospitalization. Partial response was achieved in 14% (3/21) of patients. Median PFS for all patients was 1.7 months (95% CI 0‐3.9); median OS for all patients was 1.7 months (95% CI 0‐4.2); and the 4‐month survival probability was 36% (95% CI 25%‐47%). In this retrospective study, patients with intermediate‐risk or poor‐risk mRCC who are hospitalized at a large tertiary referral center for cancer‐related symptoms derive limited clinical benefit from nivo/ipi when started in the inpatient setting. Alternative, more effective systemic therapies should be considered for these patients.