bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase Ib study of anti-CSF-1R antibody emactuzumab in combination with CD40 agonist selicrelumab in advanced solid tumor patients
Authors: Machiels Jean-Pascal , Gomez-Roca Carlos , Michot Jean-Marie , Zamarin Dmitriy , Mitchell Tara , Catala Gaetan , Eberst Lauriane , Jacob Wolfgang , Jegg Anna-Maria , Cannarile Michael A , Watson Carl , Babitzki Galina , Korski Konstanty , Klaman Irina , Teixeira Priscila , Hoves Sabine , Ries Carola , Meneses-Lorente Georgina , Michielin Francesca , Christen Randolph , Rüttinger Dominik , Weisser Martin , Delord Jean-Pierre , Cassier Philippe
Published: October 2020

Background

This phase Ib study evaluated the safety, clinical activity, pharmacokinetics, and pharmacodynamics (PD) of emactuzumab (anti-colony stimulating factor 1 receptor monoclonal antibody (mAb)) in combination with selicrelumab (agonistic cluster of differentiation 40 mAb) in patients with advanced solid tumors.

Methods

Both emactuzumab and selicrelumab were administered intravenously every 3 weeks and doses were concomitantly escalated (emactuzumab: 500 to 1000 mg flat; selicrelumab: 2 to 16 mg flat). Dose escalation was conducted using the product of independent beta probabilities dose-escalation design. PD analyzes were performed on peripheral blood samples and tumor/skin biopsies at baseline and on treatment. Clinical activity was evaluated using investigator-based and Response Evaluation Criteria In Solid Tumors V.1.1-based tumor assessments.

Results

Three dose-limiting toxicities (all infusion-related reactions (IRRs)) were observed at 8, 12 and 16 mg of selicrelumab together with 1000 mg of emactuzumab. The maximum tolerated dose was not reached at the predefined top doses of emactuzumab (1000 mg) and selicrelumab (16 mg). The most common adverse events were IRRs (75.7%), fatigue (54.1%), facial edema (37.8%), and increase in aspartate aminotransferase and creatinine phosphokinase (35.1% both). PD analyzes demonstrated an increase of Ki67+-activated CD8+ T cells accompanied by a decrease of B cells and the reduction of CD14Dim CD16bright monocytes in peripheral blood. The best objective clinical response was stable disease in 40.5% of patients.

Conclusion

Emactuzumab in combination with selicrelumab demonstrated a manageable safety profile and evidence of PD activity but did not translate into objective clinical responses.

Trialregistration number

NCT02760797.
Balancing COVID-19 preparedness and ‘business as usual’ in hospitals: lessons from executives in China, Norway and the UK
Authors: Ikram Umar , Ren Hui , Shields-Zeeman Laura , Frich Jan , Northam Jones Daniel , Wu Jiong , Kuang Ming , Liu Yuanli , Ma Jing
Published: October 2020

Background

During the first wave of COVID-19 pandemic, hospitals were forced to cancel or postpone non-COVID-19 care. With new outbreaks emerging, hospitals are now figuring out how to balance preparedness for future COVID-19 waves with their elective and regular services. This report discusses how four hospital systems deal with these dual responsibilities in China, Norway and the UK.

Reflections

Based on the experiences and combined reflections of hospital executives, we have formulated five strategic and leadership lessons for hospitals as they manage these dual responsibilities. (1) Redesign organisation to separate COVID-19 and non-COVID-19 services both within and across hospitals. (2) Expand virtual care strategies to improve access. (3) Use data-driven models to allocate resources across COVID-19 and non-COVID-19 units. (4) Invest in programmes to promote frontline staff well-being. (5) Secure financial support to continue to deliver on the dual responsibilities.

Conclusion

The COVID-19 pandemic gives rise to leadership challenges that have fuelled organisational change and new approaches to healthcare delivery. Leading hospitals during the pandemic is a balancing act—providing care for both patients with COVID-19 and non-COVID-19, while at the same time preparing for the next waves of the pandemic.
Use of exhaled breath condensate (EBC) in the diagnosis of SARS-COV-2 (COVID-19)
Authors: Ryan Daniel J , Toomey Sinead , Madden Stephen F , Casey Michelle , Breathnach Oscar S , Morris Patrick G , Grogan Liam , Branagan Peter , Costello Richard W , De Barra Eoghan , Hurley Killian , Gunaratnam Cedric , McElvaney Noel G , OBrien Michael Emmet , Sulaiman Imran , Morgan Ross K , Hennessy Bryan T
Published: October 2020

False negatives from nasopharyngeal swabs (NPS) using reverse transcriptase PCR (RT-PCR) in SARS-CoV-2 are high. Exhaled breath condensate (EBC) contains lower respiratory droplets that may improve detection. We performed EBC RT-PCR for SARS-CoV-2 genes (E, S, N, ORF1ab) on NPS-positive (n=16) and NPS-negative/clinically positive COVID-19 patients (n=15) using two commercial assays. EBC detected SARS-CoV-2 in 93.5% (29/31) using the four genes. Pre-SARS-CoV-2 era controls (n=14) were negative. EBC was positive in NPS negative/clinically positive patients in 66.6% (10/15) using the identical E and S (E/S) gene assay used for NPS, 73.3% (11/15) using the N/ORF1ab assay and 14/15 (93.3%) combined.
Calculations on the non-classical β-hydride elimination observed in trans-(H)(OMe)-Ir(Ph)(PMe3)3: possible production and reaction of methyl formate
Authors: Ataya Mohamad , Hasanayn Faraj
Published: October 2020

The octahedral trans hydrido-alkoxide complex trans-(H)(OMe)-Ir(Ph)(PMe3)3 (2-OCH3) was prepared by Milstein and coworkers by addition of methanol to Ir(Ph)(PMe3)3 (1). 2-OCH3 was discovered to undergo a methanol catalyzed outer-sphere carbonyl de-insertion in which a vacant coordination site is not required. The reaction yields the octahedral trans dihydride complex trans-(H)2-Ir(Ph)(PMe3)3 (2-H) as a kinetic product along with formaldehyde derivatives reported as [CH2=O]x. We investigate the mechanism and products of this reaction using density functional theory. The de-insertion transition state has an ion-pair character leading to a high barrier in benzene continuum: ΔG ‡ = 27.9 kcal/mol. Adding one methanol molecule by H-bonding to the alkoxide of 2-OCH3 lowers the barrier to 22.7 kcal/mol. When the calculations are conducted in a methanol continuum, the barrier drops to 8.8 kcal/mol. However, the thermodynamics of de-insertion are endergonic by near 5 kcal/mol in both benzene and methanol. The calculations identify a low energy outer-sphere H/OMe metathesis pathway that transforms the formaldehyde and another 2-OCH3 molecule directly into a second 2-H complex and methyl formate. Likewise, a second H/OCH3 metathesis reaction interconverting methyl formate and 2-OCH3 into 2-H and dimethyl carbonate is computed to be exergonic and kinetically facile. These results imply that the production of methyl formate and dimethyl carbonate from 2-OCH3 is plausible in this system. The net transformation from the square planar 1 and methanol to 2-H and either methyl formate or dimethyl carbonate would represent a unique stoichiometric dehydrogenative coupling reaction taking place at room temperature by an outer-sphere mechanism.
Participation of the opioid receptor – nitric oxide – cGMP – K+channel pathway in the peripheral antinociceptive effect of nalbuphine and buprenorphine in rats
Authors: Ortiz Mario I. , Cariño-Cortés Raquel , Castañeda-Hernández Gilberto
Published: October 2020

The aim of this study was to examine if the peripheral antinociceptive effects of the opioid agonist/antagonist nalbuphine and buprenorphine involve the sequential participation of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) synthesis followed by K+channel opening in the formalin test. Wistar rats (180–220 g) were injected in the dorsal surface of the right hind paw with formalin (1%). Rats received a subcutaneous (s.c.) injection into the dorsal surface of the paw of vehicles or increasing doses of nalbuphine (50–200 μg/paw) or buprenorphine (1–5 μg/paw) 20 min before formalin injection into the paw. Nalbuphine antinociception was reversed by the s.c. injection into the paw of the inhibitor of NO synthesis (NG-nitro-l-arginine methyl ester (L-NAME)), by the inhibitor of guanylyl cyclase (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ)), by the Kir6.1–2, ATP-sensitive K+channel inhibitors (glibenclamide and glipizide), by the KCa2.1–3, small conductance Ca2+-activated K+channel blocker (apamin), by the KCa1.1, large conductance Ca2+-activated K+channel blocker (charybdotoxin), and by the KV, voltage-dependent K+channel inhibitors (4-aminopyridine (4-AP) and tetraethylammonium chloride (TEA)). The antinociceptive effect produced by buprenorphine was blocked by the s.c. injection of 4-AP and TEA but not by L-NAME, ODQ, glibenclamide, glipizide, apamin, or charybdotoxin. The present results provide evidence for differences in peripheral mechanisms of action between these opioid drugs.
Involvement of G proteins and Rho kinase in α1-adrenoceptor mediated contractions of the rat portal vein
Authors: Alsufyani Hadeel A. , Docherty James R.
Published: October 2020

Contractions of the rat portal vein in response to the α1-adrenoceptor agonist phenylephrine consist of phasic contractions at low concentrations, with tonic contractions superimposed at higher concentrations. The α1D-adrenoceptor antagonist BMY7378 (7.0, –log M) did not affect phasic or tonic contractions to phenylephrine. The relatively nonselective α1-adrenoceptor antagonist prazosin (7.5) shifted equally the potencies of phenylephrine at producing phasic and tonic contractions, with pKB values of 8.85 and 8.83 (–log M), respectively. The α1A-adrenoceptor antagonist RS100329 (8.5) produced a significantly greater shift in phenylephrine potency for phasic (pKB of 10.51) than tonic contractions (pKB of 9.78). Prazosin was less effective than RS100329 at reducing the effects of phenylephrine on frequency of phasic contractions. The Rho kinase inhibitor fasudil (5.0) did not affect phasic contractions to phenylephrine, but significantly reduced tonic contractions. It is concluded that there is no evidence for involvement of α1D-adrenoceptors in responses of the rat portal vein to phenylephrine, but phasic responses involve predominantly α1A-adrenoceptors. Tonic responses may involve predominantly α1B-adrenoceptors and are at least partly mediated by mechanisms involving Rho kinase sensitive to fasudil.
Improved $$(g-2)_\mu $$ measurements and supersymmetry
Authors: Chakraborti Manimala , Heinemeyer Sven , Saha Ipsita
Published: October 2020

The electroweak (EW) sector of the Minimal Supersymmetric Standard Model (MSSM) can account for variety of experimental data. The lighest supersymmetric particle (LSP), which we take as the lightest neutralino, $${\tilde{\chi }}_{1}^0$$

χ
~

1

0

, can account for the observed Dark Matter (DM) content of the universe via coannihilation with the next-to-LSP (NLSP), while being in agreement with negative results from Direct Detection (DD) experiments. Owing to relatively small production cross-sections a comparably light EW sector of the MSSM is also in agreement with the unsuccessful searches at the LHC. Most importantly, the EW sector of the MSSM can account for the persistent $$3-4\,\sigma $$

3
-
4

σ

discrepancy between the experimental result for the anomalous magnetic moment of the muon, $$(g-2)_\mu $$

(
g
-
2
)

μ

, and its Standard Model (SM) prediction. Under the assumption that the $${\tilde{\chi }}_{1}^0$$

χ
~

1

0

provides the full DM relic abundance we first analyze which mass ranges of neutralinos, charginos and scalar leptons are in agreement with all experimental data, including relevant LHC searches. We find an upper limit of $$\sim 600 \,\, \mathrm {GeV}$$

∼
600

GeV

for the LSP and NLSP masses. In a second step we assume that the new result of the Run 1 of the “MUON G-2” collaboration at Fermilab yields a precision comparable to the existing experimental result with the same central value. We analyze the potential impact of the combination of the Run 1 data with the existing $$(g-2)_\mu $$

(
g
-
2
)

μ

data on the allowed MSSM parameter space. We find that in this case the upper limits on the LSP and NLSP masses are substantially reduced by roughly $$100 \,\, \mathrm {GeV}$$

100

GeV

. This would yield improved upper limits on these masses of $$\sim 500 \,\, \mathrm {GeV}$$

∼
500

GeV

. In this way, a clear target could be set for future LHC EW searches, as well as for future high-energy $$e^+e^-$$

e
+

e
-

 colliders, such as the ILC or CLIC.
Specific entropy as a clock for the evolutionary quantization of the isotropic Universe
Authors: Campolongo Andrea , Montani Giovanni
Published: October 2020

In this paper, we analyze the dynamics of an isotropic closed Universe in presence of a cosmological constant term and we compare its behavior in the standard Wheeler–DeWitt equation approach with the one when a Lagrangian fluid is considered in the spirit of the Kuchar–Brown paradigm. In particular, we compare the tunnelling of the Universe from the classically forbidden region to the allowed one, showing that considering a time evolution deeply influences the nature of the model. In fact, we show that in the presence of the Lagrangian fluid, the cosmological singularity is restored both in the classical and the quantum regime. However, in the quantum regime the singularity is probabilistically suppressed for some energy eigenvalues and in the case the latter is equal to zero one recovers the standard WDW case. Finally, we introduce a cut-off physics feature in the Minisuperspace by considering a Polymer quantum mechanical approach limiting our attention to the semi-classical dynamics mainly (the quantum treatment is inhibited by the non-local nature of the Hamiltonian operator). We show that the singularity is again removed, like in the fluid-free model, and a bouncing cosmology emerges so that the present model could mimic a cyclic cosmology.
Additional symmetries of the Two-Boson hierarchy and the multi-component Two-Boson hierarchy
Authors: Li Jian , Xia Tiecheng
Published: October 2020

In this paper, we firstly recall some basic facts on the Two-Boson hierarchy. Then, introducing some time variables that consist of a non-abelian Lie algebra. Next, we construct additional symmetries for the Two-Boson hierarchy with the aid of the Orlov–Schulman operator, which depend on the time variables and dressing operator. In addition, we give the additional flow equations of the Two-Boson hierarchy as a simple example, and prove that the additional flows are symmetries of the Two-Boson hierarchy. In this way, an isomorphism between the additional symmetries of the Two-Boson hierarchy and the [Formula: see text] algebra is constructed. Finally, the multi-component Two-Boson hierarchy can be defined, and we consider the additional symmetries for the multi-component Two-Boson hierarchy with the method of Dickey, Orlov, and Shulman.
SmartDR
Authors: Gonçalves Stèphano M. M. , Rosa Jr Leomar S. da , Marques Felipe S.
Published: October 2020

Detailed routing is one of the most time-consuming steps of physical synthesis of integrated circuits. Also, it is very challenging due to the complexity of the design rules that the router must obey. In this article, we present SmartDR, a detailed routing system that focuses on good design rule handling and fast runtime. To attend these objectives, we propose a novel pin access approach and a fast design rule aware A*-interval-based path search algorithm. The pin access method uses resource sharing ghost pin access paths with dynamic legalization check. We also propose a design rule check algorithm to detect thick metal shapes that are widely created using the proposed pin access method. The path search algorithm integrates design rule check on its core, handling many design rules that would not be possible to be solved by postprocessing. It is aware of the minimum area rule, the cut spacing of via cuts within the same path, and the via library. We also present a new technique to improve A*-based path search in detailed routing. The technique makes the path search algorithm aware of the global routing guides, accelerating the search. Using ISPD 2018 Contest benchmarks, our experiments show that our router is superior to the state-of-the-art routers that were also tested using the same benchmarks. Our router has presented, on average, 77.6% less runtime, 73.5% less design rule violations, with respect to Dr. CU 2.0, which is the better of the compared routers.
Development of an Electrochemical Hydrogen Contaminant Detector
Authors: Mukundan Rangachary , Brosha Eric L. , Romero Christopher J. , Poppe Daniel , Rockward Tommy
Published: October 2020

Hydrogen refueling stations (HRSs) that dispense hydrogen to fuel cell vehicles need to ensure the quality of hydrogen to avoid contamination of the vehicle’s expensive fuel cell stacks. Currently, stations verify their fuel quality only periodically to ensure that they meet the strict fuel quality standards specified by either International Organization for Standards (ISO) or Society for Automotive Engineers (SAE). The development of hydrogen contaminant detectors (HCDs) that can provide low cost continuous monitoring at the HRS can be an invaluable asset in protecting fuel cell vehicles from any fuel contamination in-between infrequent expensive analysis of hydrogen fuel quality. An HCD capable of detecting < 200 ppb of CO in hydrogen is presented in this paper. The HCD is based on an electrochemical hydrogen pumping cell whose ultra-low loaded working electrode is poisoned by the contaminant, thus reducing its hydrogen oxidation reaction rate. The hydrogen pumping cell consists of a Nafion® membrane, a sputtered Pt working electrode, a Pt/Ru counter/pseudo-reference electrode and an internal water wicking system that provides humidification to the membrane and electrodes. When this HCD is operated in a pulsed voltammetry mode, it can provide stable CO response for thousands of hours in a HRS.
SIRT1-mediated deacetylation of NF-κB inhibits the MLCK/MLC2 pathway and the expression of ET-1, thus alleviating the development of coronary artery spasm
Authors: Wu Bo-Wen , Wu Mi-Shan , Liu Yu , Lu Meng , Guo Jin-Dong , Meng Yun-Hui , Zhou Yu-Hui
Published: October 2020

Rat coronary artery spasm models exhibit reduced expression of SIRT1. Overexpression of SIRT1 inhibits contraction and proliferation of VSMCs. SIRT1 inhibits NF-κB through deacetylation to modulate VSMC contraction and proliferation. NF-κB activates the MLCK/MLC2 pathway. NF-κB upregulates ET-1 to modulate VSMC contraction and proliferation.
Dietary sodium restriction sex specifically impairs endothelial function via mineralocorticoid receptor-dependent reduction in NO bioavailability in Balb/C mice
Authors: Faulkner Jessica L. , Harwood Daisy , Kennard Simone , Antonova Galina , Clere Nicolas , Chantemèle Eric J. Belin de
Published: October 2020

Female sex confers improved endothelial relaxation and vascular constriction responses in female Balb/C mice compared with males under baseline conditions. Sodium restriction impairs endothelial function, which is nitric oxide dependent, and increases vascular contractility in association with reduced vascular endothelial nitric oxide synthase and NOX4 expression in female mice ablating the baseline sex difference. Mineralocorticoid receptor antagonism ablates sodium restriction-induced endothelial dysfunction, but not increased vascular contractility, in female mice.
Is the Real Estate Market of New Housing Stock Influenced by Urban Vibrancy?
Authors: Barreca Alice , Curto Rocco , Rolando Diana
Published: October 2020

The attractiveness and vibrancy of an urban area are very complex aspects that both Public Administrations and real estate developers and construction companies have to carefully consider in order to correctly address their investments and sustainable urban development projects. The aim of this paper is to study urban vibrancy and its relationship with the neighbourhood services and the real estate market of new housing stock. Spatial analyses are performed to study the influence of the Neighbourhood Services Index (NeSI) and its Principal Components (PCs) on listing prices and the construction activity. Spatial autoregressive (SAR) models are applied both with lattice data and data points, in order to manage spatial dependence and to identify the variables that significantly influence housing prices and construction site density. Findings highlight that the NeSI significantly influences the real estate market of new housing stock and that above the analysed neighbourhood services and the retail activities have a great, significant, and positive influence on the density of housing construction sites. The results of this study represent a real support for both public and private bodies to identify the most and least attractive and vibrant urban areas and to deal with important aspects of urban complexity.
Compressive Strength Evaluation of Fiber‐Reinforced High‐Strength Self‐Compacting Concrete with Artificial Intelligence
Authors: Nguyen Tu T. , Pham Duy Hoa , Pham Thanh Tung , Vu Hoang Hiep
Published: October 2020

This paper describes the application of two artificial intelligence‐ (AI‐) based methods to predict the 28‐day compressive strength of fiber‐reinforced high‐strength self‐compacting concrete (FRHSSCC) from its ingredients. A series of 131 data samples collected from various published literature sources were used for training, validation, and testing models. Various AI models were developed with different training algorithms and a number of nodes in the hidden layer to obtain the optimal model for the FRHSSCC data. It is shown that the performances of the artificial neural network (ANN) were better than that of the adaptive neurofuzzy inference system (ANFIS) model. Specifically, the overall coefficient of determination (R2) of the ANN and ANFIS models was 0.9742 and 0.9584, respectively. The sensitivity analysis was also conducted with the ANN model to investigate the effects of input parameters on the output. The results from the sensitivity analysis revealed that the compressive strength of FRHSSCC at 28 days was more sensitive with the changes of water by cement ratio (WCR) parameter and insensitive with varying amounts of fiber (VOF). Finally, it can be concluded that the application of artificial intelligence shows the great potential in the prediction of compressive strength of FRHSSCC.
Selection, Identification, and Application of Aptamers against Agaricus bisporus Lectin to Establish an Aptamer-AuNPs Colorimetric Method for Detection of ABL
Authors: Gao Hao , Tian Yiling , Zhang Min , Liu Jianhui , Yuan Yaowu , Tan Jianxin , Ma Aijin
Published: October 2020

Agaricus bisporus lectin (ABL), which is one of the antinutritional factors in A. bisporus, is an important allergen and harmful to human health. Due to the shortcomings of the current detection methods, it is extremely urgent to establish a rapid and sensitive detection method for ABL in foods. To isolate the ssDNA aptamer of ABL, 13 rounds of subtractive systematic evolution of ligands by exponential enrichment (SELEX) selection were carried out. As a result, six candidate aptamers were selected and further examined for their binding affinity and specificity by enzyme-linked aptamer method. One aptamer (seq-41) against ABL with a high affinity and specificity was isolated and demonstrated to be the optimal aptamer whose dissociation constant reaches the nanomolar level, Kd = 31.17 ± 0.1070 nM. Based on seq-41, an aptamer-AuNPs colorimetric method was established to detect ABL with a linear range of 0.08∼1.70 μg/mL and the detection limit is 0.062 μg/mL. This study provides a novel aptamer-AuNPs colorimetric method with high sensitivity and specificity for detection of ABL and a novel strategy for development of detection method of fungal or plant allergens.
Acceptance Tendency of High-Level Taxis: From the Passengers’ Perspective
Authors: Jou Rong-Chang , Chen Ke-Hong
Published: October 2020

In the present study, we used the stated preference approach to design different situations, including appearance, different services, and different times to further explore passengers’ acceptance of and expected price to be paid for taxi service levels. In addition to using general ordered models, the results of this study were also compared with the multinomial logit model and the partial proportional odds (PPO) model. The results of comparison between the models ultimately revealed that the PPO model statistically had a better explanatory power. In the model estimation results, the key explanatory variables included the ability to recognize the appearance, seating space, honorable service, the development of user payment concepts, and demographic grouping, all of which could increase acceptance. The results obtained in this study could provide a key reference for the classification of taxis in the Taiwan region and serve as a basis for the development of strategies by operators in the future.
The Clinical Value and Variation of Antithyroid Antibodies during Pregnancy
Authors: Li Chuyu , Zhou Jing , Huang Zengshu , Pan Xinyao , Leung Wingting , Chen Lijia , Zhang Yanzhi , Wang Lan , Sima Yizhen , Gober Hans-Jürgen , Zhang Na , Qiu Xuemin , Li Lisha , Guan Liang , Wang Ling
Published: October 2020

Antithyroid antibodies, which include thyroid-stimulating hormone receptor antibodies (TRAbs), thyroid peroxidase antibodies (TPOAbs), and thyroid globulin antibodies (TgAbs), are widely known for their tight association with thyroid autoimmune diseases. The variation in all three kinds of antibodies also showed different trends during and after pregnancy (Weetman, 2010). This article reviewed the the physiological changes, while focusing on the variation of thyroid antibodies concentration in women during and after pregnancy, and adverse consequences related to their elevation. Since abnormal elevations of these antithyroid antibodies may lead to adverse outcomes in both mothers and fetuses, special attention must be paid to the titer of the antibodies during pregnancy. The molecular mechanisms of the variations in those antibodies have yet to be explained. The frequency and timing of thyroid antibody measurement, as well as different reference levels, also remain to be elucidated.
The Effects of County Public Hospital Reform on the Consumption and Costs of Antibiotics: Evidence from a Quasinatural Experiment in Jiangsu, China
Authors: Wang Ying , Zhu Yulei , Liu Xiaoliang , Xu Xinglu , Fang Wenqing , Li Xin
Published: October 2020

Background. Overuse of antibiotics is a major driver for rapid spread of antimicrobial resistance worldwide, particularly common in China. The close linkage between hospital revenue and sales of drugs has become the key incentive for overprescription of antibiotics. Since 2009, the Chinese government implemented a series of measures to cut off the link, including removing the markup of drugs, increasing financial subsidies, and adjusting charges for medical service. Objective. To evaluate the impacts of county public hospital reform on the consumption and costs of procured antibiotics in Jiangsu province. Methods. A quasiexperiment design was conducted in Jiangsu province where 99 county public hospitals implemented the reform successively in different periods. Of these, 37 county public hospitals implemented the reform since January 2013, which were regarded as the intervention group, and the remaining 62 hospitals were included in the control group. A difference‐in‐differences (DID) analysis with generalized linear regressions was used on the procurement records of antibiotics from January 2012 to December 2013. Modified Park test was used for family distribution and Box–Cox test for log link. Placebo tests were employed to test the common‐trend hypothesis of two groups. Results. For the intervention group, the average volume of procured restricted antibiotics and injectable antibiotics increased by 24.12% and 2.75% while the costs increased by 19.01% and 9.09%, respectively. The average costs per DDD of restricted and injectable antibiotics were much higher than unrestricted and oral antibiotics. The DID results showed that the reform had a positive impact on the average volume (p = 0.005) and costs (p = 0.001) of nonrestricted antibiotics. In addition, the implementation of the reform was associated with a reduction in volume (p = 0.031) and costs (p = 0.043) of procured oral antibiotics. The reform also contributed to an increase in average costs per DDD of total antibiotics (p = 0.049). Conclusions. The reform is effective in reducing the consumption and costs of unrestricted and oral antibiotics, but it has failed to reduce the consumption and costs of expensive restricted and injectable antibiotics, leading to increased burden of diseases. It is critical that the health policy initiatives can deincentivize overuse of antibiotics at both hospital and individual physician’s levels. The reform should enforce government financial support, improve hospital governance, optimize performance evaluation, and establish specialized management approach for antibiotic use.
Sexual Dysfunction in Postmenopausal Women with Breast Cancer on Adjuvant Aromatase Inhibitor Therapy
Authors: Lubián López Daniel María , Butrón Hinojo Carmen Aisha , Sánchez-Prieto Manuel , Mendoza Nicolás , Sánchez-Borrego Rafael
Published: October 2020

Introduction: The aim of this study was to investigate whether postmenopausal women with breast cancer (BC) on adjuvant aromatase inhibitor (AI) therapy have a higher prevalence of female sexual dysfunction (FSD). Second, the aim was to determine the quality of life (QoL) and level of anxiety depending on whether or not they are AI users. Methods: A prospective cross-sectional study involving 168 patients was performed. Three questionnaires were carried out: sexual functioning was evaluated with the Female Sexual Function Index (FSFI), while the EORTC QLQ-BR23 measures to study QoL in patients with BC and the State-Trait Anxiety Inventory (STAI) questionnaire (trait and status) were used to assess anxiety status in patients under treatment with AIs or not. Results: 47.6% (80/168) of the postmenopausal BC survivors were not sexually active (mean time after surgery: 48.6 months) despite a relatively low mean age (56.43 years). Postmenopausal AI-treated women had significantly worse sexual function as measured by the FSFI (23.40 ± 5.26 vs. 30.16 ± 2.24; p = 0.000). There were significant differences between both groups in all domains, except orgasm. The QoL score was 37.67 ± 7.38 in AI users versus 39.00 ± 1.44 among nonusers (p = 0.053). Patients under endocrine treatment also presented STAI scores significantly higher (25.83 ± 4.99 vs. 19.00 ± 7.12; p = 0.000). Trait anxiety was high in both groups, but this was not statistically significant. Conclusions: We observed a high prevalence of sexual inactivity among BC survivors regardless of AI use. Patients with AI use presented significantly higher prevalence of FSD, worse QoL, and greater anxiety.
Fine Needle Aspiration versus Fine Needle Biopsy of Biliopancreatic Lesions: Are They Really Opposing Techniques or Can They Be Complementary? Our Experience in a Large Cohort of Cases from a Single Institution
Authors: Nicola Marta , Onorati Monica , Albertoni Milena Maria , Bianchi Chiara Luisa , De Nucci Germana , Mandelli Enzo Domenico , Nicola Lidia , Di Nuovo Franca
Published: October 2020

Introduction: Nowadays, endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA), and fine needle biopsy (FNB) are considered the best procedures for the diagnosis of biliopancreatic lesions. These methods represent a milestone since they proved to be both safe for the patient and useful to achieve diagnostic material useful to plan the best treatment strategy. Objective: Since in the literature, a debate between cytology and histology supporters is still ongoing and the trend is changing in favor of FNB, we would like to present our experience about the diagnostic yield of FNA and FNB. The aim of our study is to highlight FNA versus FNB diagnostic role of biliopancreatic lesions, highlight advantages, and drawbacks of these procedures, and our view on these 2 procedures and whether they should still be considered complementary or opposing techniques. Methods: We retrospectively reviewed our hospital series of 469 EUS diagnostics procedures of biliopancreatic lesions performed in 419 patients, between 2015 and 2019. Results: The overall adequacy rates of FNA and FNB were, respectively, 98.9 and 100%. Stratifying cases according to anatomic location of the mass (pancreas vs. biliary system), we detected 168 malignancies out of 349 pancreatic lesions (168/349; 48.1%), while biliary system cases positive for malignancy represented 33.8% (23/68 cases) (p value = 0.045, χ2 test). As for concomitant FNB, our series displayed a high rate of diagnostic concordance (88.8%). Conclusions: Despite numerous data published, it is still unclear which is the most feasible method to use; therefore, we compared FNA, FNB, or their combination to understand the best applicable technique. Our experience confirmed that FNA is extremely efficient in the diagnosis of biliopancreatic lesions, especially in the hands of expert endoscopists and pathologists. Considering anatomic location, EUS-FNA is more accurate for mass-forming neoplasms in the pancreatic parenchyma rather than for lesions of the biliary system. Moreover, concomitant FNB usually confirmed the cytological diagnosis, allowing a deeper immunohistochemical characterization of the neoplasia. This proves that a “pure” cytology and “pure” histology approach should be looked differently since these are complementary techniques especially if we can obtain a cellblock from FNA.
Ibrutinib-Mediated Atrial Fibrillation Attributable to Inhibition of C-Terminal Src Kinase
Authors: Xiao Ling , Salem Joe-Elie , Clauss Sebastian , Hanley Alan , Bapat Aneesh , Hulsmans Maarten , Iwamoto Yoshiko , Wojtkiewicz Gregory , Cetinbas Murat , Schloss Maximilian J. , Tedeschi Justin , Lebrun-Vignes Bénédicte , Lundby Alicia , Sadreyev Ruslan I. , Moslehi Javid , Nahrendorf Matthias , Ellinor Patrick T. , Milan David J
Published: October 2020

Background:

Ibrutinib is a Bruton tyrosine kinase inhibitor with remarkable efficacy against B-cell cancers. Ibrutinib also increases the risk of atrial fibrillation (AF), which remains poorly understood.

Methods:

We performed electrophysiology studies on mice treated with ibrutinib to assess inducibility of AF. Chemoproteomic analysis of cardiac lysates identified candidate ibrutinib targets, which were further evaluated in genetic mouse models and additional pharmacological experiments. The pharmacovigilance database, VigiBase, was queried to determine whether drug inhibition of an identified candidate kinase was associated with increased reporting of AF.

Results:

We demonstrate that treatment of mice with ibrutinib for 4 weeks results in inducible AF, left atrial enlargement, myocardial fibrosis, and inflammation. This effect was reproduced in mice lacking Bruton tyrosine kinase, but not in mice treated with 4 weeks of acalabrutinib, a more specific Bruton tyrosine kinase inhibitor, demonstrating that AF is an off-target side effect. Chemoproteomic profiling identified a short list of candidate kinases that was narrowed by additional experimentation leaving CSK (C-terminal Src kinase) as the strongest candidate for ibrutinib-induced AF. Cardiac-specific Csk knockout in mice led to increased AF, left atrial enlargement, fibrosis, and inflammation, phenocopying ibrutinib treatment. Disproportionality analyses in VigiBase confirmed increased reporting of AF associated with kinase inhibitors blocking Csk versus non-Csk inhibitors, with a reporting odds ratio of 8.0 (95% CI, 7.3–8.7;
P
<0.0001).

Conclusions:

These data identify Csk inhibition as the mechanism through which ibrutinib leads to AF.

Registration:

URL:
https://ww.clinicaltrials.gov
; Unique identifier: NCT03530215.
Cardiac and Kidney Benefits of Empagliflozin in Heart Failure Across the Spectrum of Kidney Function
Authors: Zannad Faiez , Ferreira João Pedro , Pocock Stuart J. , Zeller Cordula , Anker Stefan D. , Butler Javed , Filippatos Gerasimos , Hauske Sibylle Jenny , Brueckmann Martina , Pfarr Egon , Schnee Janet , Wanner Christoph , Packer Milton
Published: October 2020

Background:

In EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction), empagliflozin reduced cardiovascular death or heart failure (HF) hospitalization and total HF hospitalizations, and slowed the progressive decline in kidney function in patients with HF and a reduced ejection fraction, with and without diabetes. We aim to study the effect of empagliflozin on cardiovascular and kidney outcomes across the spectrum of kidney function.

Methods:

In this prespecified analysis, patients were categorized by the presence or absence of chronic kidney disease (CKD) at baseline (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m
2
or albumin-to-creatine ratio >300 mg/g). The primary and key secondary outcomes were: (1) a composite of cardiovascular death or HF hospitalization (primary outcome); (2) total HF hospitalizations; and (3) eGFR slope. The direct impact on kidney events was investigated by a prespecified composite kidney outcome (defined as a sustained profound decline in eGFR, chronic dialysis, or transplant). The median follow-up was 16 months.

Results:

Of 3730 patients who were randomized to empagliflozin or placebo, 1978 (53%) had CKD. Empagliflozin reduced the primary outcome and total HF hospitalizations in patients with and without CKD: hazard ratio (HR)=0.78 (95% CI, 0.65–0.93) and HR=0.72 (95% CI, 0.58–0.90), respectively (interaction
P
=0.63). Empagliflozin slowed the slope of eGFR decline by 1.11 (0.23–1.98) ml/min/1.73 m
2
/yr in patients with CKD and by 2.41 (1.49–3.32) ml/min/1.73 m
2
/yr in patients without CKD. The risk of the composite kidney outcome was reduced similarly in patients with and without CKD: HR=0.53 (95% CI, 0.31–0.91) and HR=0.46 (95% CI, 0.22–0.99), respectively. The effect of empagliflozin on the primary composite outcome and key secondary outcomes was consistent across a broad range of baseline kidney function, measured by clinically relevant eGFR subgroups or by albuminuria, including patients with eGFR as low as 20 ml/min/1.73 m
2
. Empagliflozin was well tolerated in CKD patients.

Conclusions:

In EMPEROR-Reduced, empagliflozin had a beneficial effect on the key efficacy outcomes and slowed the rate of kidney function decline in patients with and without CKD, and regardless of the severity of kidney impairment at baseline.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03057977.
Impact of Myocardial Bridge on Life‐Threatening Ventricular Arrhythmia in Patients With Implantable Cardioverter Defibrillator
Authors: Okada Kozo , Hibi Kiyoshi , Ogino Yutaka , Maejima Nobuhiko , Kikuchi Shinnosuke , Kirigaya Hidekuni , Kirigaya Jin , Sato Ryosuke , Nakahashi Hidefumi , Minamimoto Yugo , Kimura Yuichiro , Akiyama Eiichi , Matsuzawa Yasushi , Iwahashi Noriaki , Kosuge Masami , Ebina Toshiaki , Tamura Kouichi , Kimura Kazuo
Published: October 2020

Background

Myocardial bridge (MB), common anatomic variant, is generally considered benign, while previous studies have shown associations between MB and various cardiovascular pathologies. This study aimed to investigate for the first time possible impact of MB on long‐term outcomes in patients with implantable cardioverter defibrillator, focusing on life‐threatening ventricular arrhythmia (LTVA).

Methods and Results

This retrospective analysis included 140 patients with implantable cardioverter defibrillator implantation for primary (n=23) or secondary (n=117) prevention of sudden cardiac death. Angiographically apparent MB was identified on coronary angiography as systolic milking appearance with significant arterial compression. The primary end point was the first episode(s) of LTVA defined as appropriate implantable cardioverter defibrillator treatments (antitachyarrhythmia pacing and/or shock) or sudden cardiac death, assessed for a median of 4.5 (2.2–7.1) years. During the follow‐up period, LTVA occurred in 37.9% of patients. Angiographically apparent MB was present in 22.1% of patients; this group showed younger age, lower rates of coronary risk factors and ischemic cardiomyopathy, higher prevalence of vasospastic angina and greater left ventricular ejection fraction compared with those without. Despite its lower risk profiles above, Kaplan–Meier analysis revealed significantly lower event‐free rates in patients with versus without angiographically apparent MB. In multivariate analysis, presence of angiographically apparent MB was independently associated with LTVA (hazard ratio, 4.24; 95% CI, 2.39–7.55;
P
<0.0001).

Conclusions

Angiographically apparent MB was the independent determinant of LTVA in patients with implantable cardioverter defibrillator. Although further studies will need to confirm our findings, assessment of MB appears to enhance identification of high‐risk patients who may benefit from closer follow‐up and targeted therapies.
A new name, synonyms, and typifications in Eugenia (Myrtaceae) from São Paulo, Brazil

Authors: VALDEMARIN KARINNE SAMPAIO , FARIA JAIR EUSTÁQUIO QUINTINO DE , SOBRAL MARCOS , BÜNGER MARIANA , MAZINE FIORELLA F.
Published: October 2020

Eugenia is an important genus of Brazilian Myrtaceae due to its representativity, ecological and economic aspects. During a study on the taxonomy of Eugenia for the “Flora Fanerogâmica do Estado de São Paulo” project, some names in need of nomenclatural and taxonomic changes were identified. A new name, and six new synonyms are herein presented, as well as the designation of ten lectotypes, two epitypes, one neotype, and the elucidation of a not validly published name, including a discussion of each case.
Stigmatodon attenuatoides (Tillandsioideae, Bromeliaceae): a new mat-forming species on inselbergs of southeastern Brazil

Authors: COUTO DAYVID RODRIGUES , MANHÃES VITOR DA CUNHA , COSTA ANDREA FERREIRA DA
Published: October 2020

During the taxonomic revision of the genus Stigmatodon, we found an unknown epilithic mat-forming species, morphologically close to S. belloi, on vertical granitic surfaces on inselbergs in southern Espírito Santo state, Brazil. We described and illustrated the new species, including a comparative analysis of characters that distinguish it from similar species. We also provide data on habitat, ecology, geographical distribution and evaluation about its threat of extinction according to the criteria of the IUCN.
Aloe ×retiefii (Asphodelaceae subfam. Alooideae), a new nothospecies from northeastern South Africa, with A. globuligemma and A. marlothii as parents

Authors: SMITH GIDEON F.
Published: October 2020

Aloe marlothii Berger (1905: 87) (Asphodelaceae subfam. Alooideae) (Fig. 1), a single-stemmed, tree-like aloe, occurs widespread in northeastern South Africa and adjacent parts of Botswana, for example near Lobatse in the southeast of the country from where it was originally described (Fig. 2), Zimbabwe, and Mozambique (see maps in Klopper & Smith 2010: 92, Fig. 32 and Van Wyk & Smith 2014: 68). Wherever A. marlothii co-occurs with other species of Aloe Linnaeus (1753: 319), hybrids are produced (Reynolds 1950, Smith & Figueiredo 2015). Aloe globuligemma Pole-Evans (1915: 30, Plates X [Figs 1 and 2] and XI [Figs 1, 2, and 3]) (Fig. 3), a stemless, medium-sized aloe, is restricted to the more subtropical parts of northeastern South Africa, southern Zimbabwe, and Mozambique (see map in Van Wyk & Smith 2014: 158). Where these two species, A. globuligemma and A. marlothii, co-occur, for example at Lebowakgomo, about 50 km southeast of Polokwane, the capital of South Africa’s Limpopo province, a bewildering range of striking hybrids with considerable horticultural potential are found (Reynolds 1950: 446, 484, Retief 2018). This hybrid also occurs a bit further south of the Lebowakgomo location, as well as elsewhere in the Limpopo province, in Sekhukhuneland in the vicinity of Steelpoort and Ohrigstad.
Ophioglossum chaloneri: A new species of Ophioglossum (Ophioglossaceae: Pteridophyta) from India

Authors: GOSWAMI HIT KISHORE , PATEL MITESH , NAG KRISHNA K.
Published: October 2020

In the present study, we describe Ophioglossum chaloneri as a new species from the Hurdulu forest area, near Ranchi (Jharkhand, India), on the basis of morphological, palynological, cytological, and molecular analyses. The new species can be distinguished from all other congeners of genus Ophioglossum in having their unusually small linear rhizome with a long stalk of trophophore, a sporophore arising from a distance from the base of the trophophore hence not always adnate or appearing inserted at the base. Triradiate, round spores show small tubercles towards the proximal pyramidal area and irregular smooth elevated exine striations on both the proximal and distal faces. The ventral face of the trophophore is unusually thin all around margin thereby showing thin whitish margin from the lower side, a situation that may be due to lack of chloroplast all around the margin at the lower face of the trophophore. This feature is not observed in any other species of the genus. Molecular study based on three chloroplast DNA sequences (cpDNA) rbcL, trnL-F, and psbA-trnH also supports O. chaloneri as a distinct species.
A new species of Carlogonus Demange, 1961 from southern India (Spirostreptida, Harpagophoridae, Harpagophorinae), with phylogenetic analysis and species-group divisions in the genus
Authors: SANKARAN PRADEEP M. , SEBASTIAN POTHALIL A.
Published: October 2020

The genus Carlogonus Demange, 1961, is diagnosed, and its relationship with other members of the Harpurostreptini Hoffman, 1980 is discussed. A new species, Carlogonus gayathri sp. nov. is described and illustrated from the southern Indian State of Kerala, and its DNA barcoding data is presented. Phylogenetic analysis based on mtDNA sequence data revealed that Carlogonus is sister-taxon to Thyropygus Pocock, 1894. Two species-groups are recognised in Carlogonus: the exaratus-group is characterised by a single tibial spine on the gonopod, while the acifer-group has paired tibial spines. A dichotomous key is presented for the known Carlogonus spp., and the current distribution of the genus is mapped.
Notes on the genus Paracyriothasastes Breuning, 1978 (Coleoptera: Cerambycidae: Lamiinae: Lamiini)
Authors: HUANG GUI-QIANG , ZHAO XIN-XIA , YAN KAI , LI SONG , ZHANG GUI-MEI
Published: October 2020

The monotypic genus Paracyriothasastes Breuning, 1978 was established for Cereopsius marmoreus Pascoe, 1857 from Malaysia. Uraechoides Breuning, 1981 was established for Uraechoides vivesi Breuning, 1981 also from Malaysia, and is currently composed of the type species and U. taomeiae Hayashi, Nara & Yu, 1995, the latter from China (Taiwan) (Tavakilian & Chevillotte 2020).
On Surf Zone Fluid Dynamics
Authors: Mellor George
Published: October 2020

There have been several numerical models developed to represent the phase-averaged flow in the surf zone, which is characterized by kD less than unity, where k is wavenumber and D is the water column depth. The classic scenario is that of surface gravity waves progressing onto a shore that create an offshore undertow current. In fact, in some models, flow velocities are parameterized assuming the existence of an undertow. The present approach uses the full vertically dependent continuity and momentum equations and the vertically dependent wave radiation stress in addition to turbulence equations. The model is applied to data that feature measurements of wave properties and also cross-shore velocities. In this paper, both the data and the model application are unidirectional and the surface stress is nil, representing the simplest surf zone application. Breaking waves are described empirically. Special to the surf zone, it is found that a simple empirical adjustment of the radiation stress enables a favorable comparison with data. Otherwise, the model applies to the open ocean with no further empiricism. A new bottom friction algorithm had been derived and is introduced in this paper. In the context of the turbulence transport model, the algorithm is relatively simple.