bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of aprepitant versus desloratadine for EGFR‐TKI‐induced pruritus: A randomized phase 2 clinical trial
Authors: Zhou Ting , Zhang Yaxiong , Ma Yuxiang , Ma Wenjuan , Wu Xuan , Huang Lu , Feng Weineng , Zhou Huaqiang , Liu Jiaqing , Zhao Hongyun , Zhang Li , Yang Yunpeng , Huang Yan
Published: October 2022

Background

Pruritus is one of the most common and challenging side effects of epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) and has impaired patients' quality of life and treatment compliance. Our study evaluated the efficacy and safety of aprepitant in managing EGFR‐TKIs–related pruritus.

Methods

This randomized, double‐blind, placebo‐controlled study was conducted between December 2016 and August 2020 in China. Patients were eligible if they were 18 years or older and had histologically confirmed locally advanced or metastatic non–small cell lung cancer (NSCLC) with first onset of moderate to severe pruritus during EGFR‐TKI treatment.

Results

A total of 130 eligible patients were randomly assigned to aprepitant (n = 65) or desloratadine (n = 65) groups. The median (interquartile range [Q1, Q3]) age was 63 (54, 70) years, and 79 (60.8%) were women. Mean visual analog scale scores at baseline were 6.35 (95% confidence interval [CI], 5.89–6.82) in the aprepitant group and 5.94 (95% CI, 5.56–6.32) in the desloratadine group. After 1 week of treatment, 33 (53.2%) patients responded to aprepitant, which was significantly higher than that of 14 (23.7%) patients responded to desloratadine (p = .001). Moreover, patients in the aprepitant group had a significantly shorter response time than patients in the desloratadine group (mean [days], 13.39 [95% CI, 11.08–15.70] vs. 16.67 [95% CI, 14.19–19.13], p = .04). The most frequent drug‐related adverse events in aprepitant group and desloratadine were constipation and dry mouth, and all adverse events were grade 1–2.

Conclusions

To the authors’ knowledge, this is the first study to prospectively present that aprepitant elicited a better and faster response and mild toxicity for managing EGFR‐TKI induced pruritus than desloratadine.

Trial registration

ClinicalTrials.gov Identifier: NCT02646020.
Improving lung cancer detection using faster region‐based convolutional neural network aided with fuzzy butterfly optimization algorithm
Authors: Sinthia P. , Malathi M. , K. Anitha , Suresh Anand M.
Published: October 2022

Lung cancer is the most deadly type of cancer and it is caused by genetic variations in lung tissues. Other causes of lung cancer are alcohol, smoking, and threatening gas exposures. The diagnosis of lung cancer is an intricate task and early detection of lung cancer can help to get the exact treatment in advance. The application of a computer‐aided diagnosis process helps to predict lung cancer earlier, nonetheless, it does not provide better accuracy. The overfitting nature of features and dimensionality of lung cancer can prevent it from obtaining maximum accuracy. Hence, we proposed a novel faster region convolutional neural network (RCNN) based fuzzy butterfly optimization algorithm (FBOA) to achieve better prediction accuracy and effectiveness. The proposed Faster RCNN can provide better positioning of lung cancer swiftly and effectively and the FBOA approach can be used to perform two‐stage classification. The fuzzy rules used in the FBOA can be utilized to find the severity of the lung cancer and differentiate the Benign stage and Malignant stage effectively. The experimental analyses are performed in MATLAB simulation. The preprocessing of images is performed by different tools from MATLAB and is to format the images as required. The cancer imaging archive (TCIA) dataset is utilized to analyze the performance of the proposed method and compared with various state‐of‐art works. The performance of the proposed method is evaluated by using different evaluation metrics such as precision, recall, F‐measure, and accuracy and attained 99, 98, 99, and 97% respectively. Thus, our proposed method outperforms all the other approaches.
Modified micromarsupialization technique as an alternative primary treatment for ranulas: A case series in a resource‐challenged economy
Authors: Elnager Mutassim , Udeabor Samuel E. , Elfadeel Abosofyan S. A. , Onwuka Chidozie I. , Hamid Mashail M. M. , Alsubaie Yassin M. A.
Published: October 2022

Objectives

Ranula is one of the commonest salivary gland cysts that mostly occur due to mucus extravasation from the sublingual salivary gland. Treatment of this lesion is still somewhat shrouded in controversy and varies from conservative treatment to surgical excision of the causative gland.

Materials and methods

This was a case series in quasi‐experimental design that evaluated the outcome and complications of the modified micromarsupialization technique as a newly introduced treatment at our center for simple sublingual ranula over a 2‐year period.

Results

Twenty patients were treated by the modified micromarsupialization technique and followed up for 1 year. There was complete resolution following this technique in 17 patients (85%) with no evidence of recurrence or complications, whereas 2 patients (10%) showed partial resolution and the remaining 1 patient (5%) showed a failure and recurrence. The age of the patient, the size of the ranula, and the retention of sutures throughout the study period did not significantly affect the treatment outcome.

Conclusions

The modified micromarsupialization technique was a simple and effective treatment that should be used as a primary treatment option for simple ranulas and we recommend it to be the first‐choice treatment before surgical excision of the sublingual gland, especially in a resource‐challenged economy like ours.
Corporate social responsibility and chief executive officer wrongdoing: A fraud triangle perspective
Authors: Zhu Chunling , Zeng Ruixin , Wang Ruxi , Xiao Yihui
Published: October 2022

Although corporate social responsibility (CSR) activities may facilitate firms to meet stakeholders' demands and gain legitimacy, there is little understanding of whether and how they may bring in harmful consequences such as chief executive officer (CEO) wrongdoing. We developed a framework to explore how CSR activities lead to CEO wrongdoing based on the fraud triangle of pressure, opportunity, and rationalization. Using a sample of 530 listed firms in China that issued CSR reports between 2011 and 2018, we found a positive relationship between CSR participation and CEO wrongdoing. We also found that this positive relationship is strengthened by firms' internal capability to gain profit and their risk orientation. Our study contributes to the CSR literature by examining the potential dark side of CSR activities, and by bridging stakeholder theory and CEO wrongdoing literature.
Energy‐Resolved Mass Spectrometry as a Tool for Identification of Lignin Depolymerization Products
Authors: Dong Xueming , Mayes Heather B. , Morreel Kris , Katahira Rui , Li Yanding , Ralph John , Black Brenna A. , Beckham Gregg T.
Published: October 2022

Lignin is the largest source of bio‐based aromatic compounds in nature, and its valorization is essential to the sustainability of lignocellulosic biorefining. Characterizing lignin‐derived compounds remains challenging due to the heterogeneity of this biopolymer. Tandem mass spectrometry is a promising tool for lignin structural analytics, as fragmentation patterns of model compounds can be extrapolated to identify characteristic moieties in complex samples. This work extended previous resonance excitation‐type collision‐induced dissociation (CID) methods that identified lignin oligomers containing β–O–4, β–5, and β–β bonds, to also identify characteristics of 5–5, β–1, and 4–O–5 dimers, enabled by quadrupole time‐of‐flight (QTOF) CID with energy‐resolved mass spectrometry (ERMS). Overall, QTOF‐ERMS offers in‐depth structural information and could ultimately contribute to tools for high‐throughput lignin dimer identification.
P‐Induced Permeation of Nickel into WO3 Octahedra to Form a Synergistic Catalyst for Urea Oxidation**
Authors: Xu Wenjuan , Zhu Lin , Sun Zejun , Xue Huichun , Guo Liutao , Feng Yanru , Li Chengrui , Li Hong , Wang Yiming , Liang Qionglin , Sun Hong‐bin
Published: October 2022

Small‐molecule induction can lead to the oriented migration of metal elements, which affords functional materials with synergistic components. In this study, phosphating nickel foam (NF)‐supported octahedral WO3 with phosphine affords P‐WO3/NF electrocatalyst. Ni is found to form Ni−P bonds that migrate from NF to WO3 under the induction of P, resulting in the complex oxides W1.3Ni0.24O4 and Ni2P2O7 in the particle interior and nickel phosphide on the octahedral grain surface. The catalytic activity of P‐WO3/NF in the urea oxidation reaction (UOR) is improved by synergistic action of the components in the synthesized hybrid particles. A current density of 10 mA cm−2 can be reached at a potential of 1.305 V, the double layer capacitance of the catalyst is significantly increased, and the electron transfer impedance in catalytic UOR is reduced. This work demonstrates that small‐molecule induction is suitable for constructing co‐catalysts with complex components in a simple protocol, which provides a new route for the design of highly efficient urea oxidation electrocatalysts.
A high step‐up DC‐DC converter based on coupled inductor and diode‐capacitor with improved voltage gain and efficiency, and reduced voltage stress for photovoltaic systems
Authors: Hajiabadi Mostafa Karimi , Mosallanejad Ali , Salemnia Ahmad
Published: October 2022

This paper proposes a nonisolated high step‐up dc‐dc converter, which optimally integrates coupled inductor, and diode‐capacitor and provides superior features such as high gain, high efficiency, and low voltage stresses on power switches. Moreover, the common ground between the input and output of the proposed converter makes it appropriate for photovoltaic systems. It consists of two power switches, one inductor, one coupled inductor (CI), four diodes, and four capacitors. The power switches are exposed to low voltage stresses and are selected from low voltage ratings and low on‐resistance semiconductors. The topology, operating principle, complete steady‐state and ac small‐signal models, loss model, and design criterion are presented and described in detail. Also, the proposed topology is compared with other previous topologies. In order to evaluate the performance of the proposed converter, a 400 V/400 W experimental prototype has been designed and built. Experimental results validate the theory and show the converter produces high gain (14.25 times in the full‐load condition tested) and operates with high efficiency (94.9% in the full‐load condition).
Can immune gene silencing via dsRNA feeding promote pathogenic viruses to control the globally invasive Argentine ant?
Authors: Felden Antoine , Dobelmann Jana , Baty James W. , McCormick Joseph , Haywood John , Lester Philip J.
Published: October 2022

Pest control methods that can target pest species with limited environmental impacts are a conservation and economic priority. Species‐specific pest control using RNA interference is a challenging but promising avenue in developing the next generation of pest management. We investigate the feasibility of manipulating a biological invader's immune system using double‐stranded RNA (dsRNA) in order to increase susceptibility to naturally occurring pathogens. We used the invasive Argentine ant as a model, targeting the immunity‐associated genes Spaetzle and Dicer‐1 with dsRNA. We show that feeding with Spaetzle dsRNA can result in partial target gene silencing for up to 28 days in the laboratory and 5 days in the field. Dicer‐1 dsRNA only resulted in partial gene knockdown after 2 days in the laboratory. Double‐stranded RNA treatments were associated with significant gene expression disruptions across immune pathways in the laboratory and to a lower extent in the field. In total, 12 viruses and four bacteria were found in these ant populations. Some changes in viral loads in dsRNA‐treated groups were observed. For example, Linepithema humile Polycipivirus 2 (LhuPCV2) loads increased after 2 days of treatment with Spaetzle and Dicer‐1 dsRNA treatments in the laboratory. After treatment with the dsRNA in the field, after 5 days the virus Linepithema humile toti‐like virus 1 (LhuTLV1) was significantly more abundant. However, immune pathway disruption did not result in a consistent increase in microbial infections, nor did it alter ant abundance in the field. Some viruses even declined in abundance after dsRNA treatment. Our study explored the feasibility of lowering a pest's immunity as a control tool. We demonstrate that it is possible to alter immune gene expression of pest species and pathogen loads, although in our specific system the affected pathogens did not appear to influence pest abundance. We provide suggestions on future directions for dsRNA‐mediated immune disruption in pest species, including potential avenues to improve dsRNA delivery as well as the importance of pest and pathogen biology. Double‐stranded RNA targeting immune function might be especially useful for pest control in systems in which viruses or other microorganisms are prevalent and have the potential to be pathogenic.
Floristic composition and turnover analysis in Dahomey Gap and the surrounding sub‐humid Togolese mountain minor forest refuges: Importance for biogeography and biodiversity conservation in sub‐Saharan Africa
Authors: Adjossou Kossi , Kokou Kouami , Deconchat Marc
Published: October 2022

The origin of Dahomey Gap (DG) flora is one of the central biogeographical questions in sub‐Saharan, which has been addressed in several studies. However, floristic evidence based on representative samples from the DG seems to be lacking in the scientific debate. The present study was conducted to fill this gap. Specifically, we assessed Togolese mountain riparian forests as minor forest refugia, examined their contribution to larger sub‐Saharan forest refugia, and discussed the significance of these findings for biogeography and biodiversity conservation. Southwest Togo, West Africa, and sub‐Saharan Upper Guinea Region Floristic data were collected in riparian forests through an intensive botanical inventory (n = 198; 50 × 10 m2). A comparative analysis was performed based on the floristic evidence related to forest refuges. The results showed significantly high species richness (868 species) and a high gamma and beta diversity associated with spatial turnover patterns. They also showed a high affinity between the study forests and large sub‐Saharan forest refugia. Riparian forests share about 60% of their current species richness with large sub‐Saharan forest refugia and contained refuge bio‐indicator species. The floristic evidence, consistent with those of other studies, suggests that Togolese mountains would have very ancient origins and have experienced paleoclimatic events. The studied riparian would have served as refuges during recurrent climatic episodes. Our results support the minimal forest fragmentation hypothesis (network of refugia along rivers). However, they seem to be incompatible with the idea that the DG flora may be essentially a relic of the early Holocene. In sub‐Saharan Africa, where maintaining a vast area of natural forest is difficult due to human pressure, efforts to preserve maximum species diversity should include a focus on the conservation of minor forest refuges, particularly in sub‐humid mountain riparian zone.
Diverse diets and low‐fiber, low‐tannin foraging preferences: Foraging criteria of Tibetan macaques (Macaca thibetana) at low altitude in Huangshan
Authors: Li Bowen , Li Wenbo , Liu Chao , Yang Peipei , Li Jinhua
Published: October 2022

Nutrient composition and food availability determine food choices and foraging strategies of animals, while altitude and geographical location affect species distribution and food availability. Tibetan macaques (Macaca thibetana) have sophisticated foraging strategies as the largest species in Macaca. They are important in understanding the ecological evolution of the entire genus. However, the mechanism of food selection in Tibetan macaques at low altitudes remains unclear. In this study, we researched a wild Tibetan macaques group (Tianhu Mountain Group, 29 individuals) living in a low‐altitude area around Mt. Huangshan, Anhui Province, China. We used instantaneous scan sampling to observe these macaques' foraging behavior from September 2020 to August 2021. We recorded the dietary composition and food availability, compared the nutrient content of staple food and non‐food items, and analyzed the role of key nutrients in food selection. We found that Tibetan macaques forage on 111 plants belonging to 93 genera and 55 families. The food types included fruits (52.5%), mature leaves (17.0%), bamboo shoots (14.4%), young leaves (6.3%), flowers (4.5%), others (2.1%), stems (1.9%), and tender shoots (1.3%). Tibetan macaques forage for a maximum of 76 plant species during spring. However, dietary diversity was highest during summer (H′ = 3.052). Monthly fruit consumption was positively correlated with food availability. Staple foods are lower in fiber, tannin, and water than non‐foods. In addition, the time spent foraging for specific foods was negatively correlated with the fiber and tannin content of the food. The results showed that Tibetan macaques' foraging plant species and food types were diverse, and their foraging strategies varied seasonally. Our findings confirmed the effect of nutrients on food choice in Tibetan macaques. We highlighted the important role of fiber and tannin in their food choices and suggested that the foraging behavior of Tibetan macaques is highly flexible and adaptive.
Association of time‐to‐intravenous furosemide with mortality in acute heart failure: data from REPORT‐HF
Authors: Ouwerkerk Wouter , Tromp Jasper , Cleland John G.F. , Angermann Christiane E. , Dahlstrom Ulf , Ertl Georg , Hassanein Mahmoud , Perrone Sergio V. , Ghadanfar Mathieu , Schweizer Anja , Obergfell Achim , Dickstein Kenneth , Filippatos Gerasimos , Collins Sean P. , Lam Carolyn S.P.
Published: October 2022

Aim

Acute heart failure can be a life‐threatening medical condition. Delaying administration of intravenous furosemide (time‐to‐diuretics) has been postulated to increase mortality, but prior reports have been inconclusive. We aimed to evaluate the association between time‐to‐diuretics and mortality in the international REPORT‐HF registry.

Methods and results

We assessed the association of time‐to‐diuretics within the first 24 h with in‐hospital and 30‐day post‐discharge mortality in 15 078 patients from seven world regions in the REPORT‐HF registry. We further tested for effect modification by baseline mortality risk (ADHERE risk score), left ventricular ejection fraction (LVEF) and region. The median time‐to‐diuretics was 67 (25th–75th percentiles 17–190) min. Women, patients with more signs and symptoms of heart failure, and patients from Eastern Europe or Southeast Asia had shorter time‐to‐diuretics. There was no significant association between time‐to‐diuretics and in‐hospital mortality (p > 0.1). The 30‐day mortality risk increased linearly with longer time‐to‐diuretics (administered between hospital arrival and 8 h post‐hospital arrival) (p = 0.016). This increase was more significant in patients with a higher ADHERE risk score (pinteraction = 0.008), and not modified by LVEF or geographic region (pinteraction > 0.1 for both).

Conclusion

In REPORT‐HF, longer time‐to‐diuretics was not associated with higher in‐hospital mortality. However, we did found an association with increased 30‐day mortality, particularly in high‐risk patients, and irrespective of LVEF or geographic region.

Clinical Trial Registration: ClinicalTrials.gov Identifier NCT02595814.
Intensity measures, fragility analysis and dimensionality reduction of rocking under far‐field ground motions
Authors: Sieber Max , Vassiliou Michalis F. , Anastasopoulos Ioannis
Published: October 2022

Problems for which it is impossible to make a precise causal prediction are commonly tackled with statistical analysis. Although fairly simple, the problem of a rocking block on a rigid base subjected to seismic excitation exhibits a fascinating, complex response, making it extremely difficult to validate numerical models against experimental results, thus calling for a statistical approach. In this context, this paper statistically studies the rocking behaviour of rigid blocks, excited by synthetic far‐field ground motions. A total of 50 million analyses are performed, considering rocking blocks of height ranging from 1 to 20 m and slenderness angle ranging from 0.1 to 0.35 rad. The results are used to explore the performance of different ground motion intensity measures (IMs), in terms of their ability to predict the maximum rocking rotation. By comparing the efficiency, sufficiency and proficiency of the IMs, it is found that the peak ground velocity (PGV) performs optimally. Then, fragility curves are constructed using different IMs, concluding again that the PGV is the most efficient IM. Impressively, the fragility curves for different block sizes collapse to a single curve, if a non‐dimensional IM that involves PGV and the block geometry is used. Finally, the results produced on the basis of far‐field synthetic motions are compared to results based on recorded ground motions.
Differences in rice yield and biomass accumulation dynamics for different direct seeding methods after wheat straw return
Authors: Tian Jinyu , Li Shaoping , Xing Zhipeng , Cheng Shuang , Guo Baowei , Hu Yajie , Wei Haiyan , Gao Hui , Liao Ping , Wei Huanhe , Zhang Hongcheng
Published: October 2022

Field experiments were performed in 2019 and 2020 to explore yield performance and biomass accumulation dynamics for different direct‐seeded rice methods after wheat straw return. The experimental treatments included two direct‐seeded rice methods (dry direct‐seeded rice and wet direct‐seeded rice) and two wheat straw return treatments (with and without wheat straw return). Wheat straw return had a negative impact on the yield and biomass of direct‐seeded rice. Compared with wet direct‐seeded rice, dry direct‐seeded rice was more negatively affected, with yield and biomass reduced by 6.7%–7.6% and 5.4%–6.5%, respectively. The yield loss was mainly associated with insufficient total spikelet numbers caused by reduced panicle numbers. A lower maximum tiller number caused by the restricted seedling tillering capacity was partly responsible for the inadequate panicle numbers in direct‐seeded rice after wheat straw return. Wheat straw return reduced the maximum and average rate of biomass accumulation, shortened the duration of effective biomass accumulation, and delayed the days to achieve the maximum rate of biomass accumulation for direct‐seeded rice. The negative effect of wheat straw return on direct‐seeded rice was concentrated mainly in the early stage; reduction in the average biomass accumulation rate in the early stage accounted for 61.1%–75.3% of the reduction in total average rate. Wet direct‐seeded rice had a higher average rate and amount of biomass accumulation at the early stage, a greater maximum tiller number, as well as a stronger photosynthetic ability and grain filling ability after heading, which contributed to improving panicle number and total spikelet number, ultimately increasing yield and biomass compared with dry direct‐seeded rice. These results demonstrate that wheat straw return reduced yield and biomass, mainly by inhibiting growth in the early stage of direct‐seeded rice. However, the wet direct‐seeding method decreased the losses in yield and biomass after wheat straw return.
Beneficial effects of arthrocen on neuroinflammation and behavior like depression in stroke in a murine model
Authors: Goudarzi Ramin , Zamanian Golnaz , Seyyedian Zahra , Mirzaee Saffari Partow , Dehpour Ahmad Reza , Partoazar Alireza
Published: October 2022

Stroke is a considerable reason for death, disability, socioeconomic loss, and depression in the world. Notably, many attempts to the reduction of the complications of poststroke injuries like depression have failed so far. In this study, we aimed to evaluate the anti‐inflammatory effect of arthrocen, avocado/soybean unsaponifiables (ASU), in the poststroke injuries like depression improvement in a mice model. We examined the antidepressant‐like effect of arthrocen using the forced swimming test and tail suspension test in mice subjected to stroke. Furthermore, immunohistochemistry of proinflammatory cytokines, IL‐10 and TNF‐α, and neural cell count were performed in the ischemic brain hippocampus of mice. Oral arthrocen reduced significantly (p < .001) the immobility time in the forced swimming test and tail suspension test in the stroke animals. Also, immunohistochemistry analysis of the hippocampus indicated significantly (p < .01) the reduction of IL‐10 and TNF‐α cytokines production. Nissl staining showed a significant (p < .0001) increase in the number of viable neurons in stroke mice receiving arthrocen. In conclusion, our data revealed the antidepressant activity of arthrocen in the stroke mice which may be the result of its anti‐inflammatory and neuroprotective role.
A comparison of multiband and multiband multiecho gradient‐echo EPI for task fMRI at 3 T
Authors: Fazal Zahra , Gomez Daniel E. P. , Llera Alberto , Marques José P. R. F. , Beck Thomas , Poser Benedikt A. , Norris David G.
Published: October 2022

A multiband (MB) echo‐planar imaging (EPI) sequence is compared to a multiband multiecho (MBME) EPI protocol to investigate differences in sensitivity for task functional magnetic resonance imaging (fMRI) at 3 T. Multiecho sampling improves sensitivity in areas where single‐echo‐EPI suffers from dropouts. However, It requires in‐plane acceleration to reduce the echo train length, limiting the slice acceleration factor and the temporal and spatial resolution Data were acquired for both protocols in two sessions 24 h apart using an adapted color‐word interference Stroop task. Besides protocol comparison statistically, we performed test–retest reliability across sessions for different protocols and denoising methods. We evaluated the sensitivity of two different echo‐combination strategies for MBME‐EPI. We examined the performance of three different data denoising approaches: “Standard,” “AROMA,” and “FIX” for MB and MBME, and assessed whether a specific method is preferable. We consider using an appropriate autoregressive model order within the general linear model framework to correct TR differences between the protocols. The comparison between protocols and denoising methods showed at group level significantly higher mean z‐scores and the number of active voxels for MBME in the motor, subcortical and medial frontal cortices. When comparing different echo combinations, our results suggest that a contrast‐to‐noise ratio weighted echo combination improves sensitivity in MBME compared to simple echo‐summation. This study indicates that MBME can be a preferred protocol in task fMRI at spatial resolution (≥2 mm), primarily in medial prefrontal and subcortical areas.
Glycine‐β‐muricholic acid antagonizes the intestinal farnesoid X receptor–ceramide axis and ameliorates NASH in mice
Authors: Jiang Jie , Ma Yuandi , Liu Yameng , Lu Dasheng , Gao Xiaoxia , Krausz Kristopher W. , Desai Dhimant , Amin Shantu G. , Patterson Andrew D. , Gonzalez Frank J. , Xie Cen
Published: October 2022

Nonalcoholic steatohepatitis (NASH) is a rapidly developing pathology around the world, with limited treatment options available. Some farnesoid X receptor (FXR) agonists have been applied in clinical trials for NASH, but side effects such as pruritus and low‐density lipoprotein elevation have been reported. Intestinal FXR is recognized as a promising therapeutic target for metabolic diseases. Glycine‐β‐muricholic acid (Gly‐MCA) is an intestine‐specific FXR antagonist previously shown to have favorable metabolic effects on obesity and insulin resistance. Herein, we identify a role for Gly‐MCA in the pathogenesis of NASH, and explore the underlying molecular mechanism. Gly‐MCA improved lipid accumulation, inflammatory response, and collagen deposition in two different NASH models. Mechanistically, Gly‐MCA decreased intestine‐derived ceramides by suppressing ceramide synthesis–related genes via decreasing intestinal FXR signaling, leading to lower liver endoplasmic reticulum (ER) stress and proinflammatory cytokine production. The role of bile acid metabolism and adiposity was excluded in the suppression of NASH by Gly‐MCA, and a correlation was found between intestine‐derived ceramides and NASH severity. This study revealed that Gly‐MCA, an intestine‐specific FXR antagonist, has beneficial effects on NASH by reducing ceramide levels circulating to liver via lowering intestinal FXR signaling, and ceramide production, followed by decreased liver ER stress and NASH progression. Intestinal FXR is a promising drug target and Gly‐MCA a novel agent for the prevention and treatment of NASH.
Examining the peatland shrubification‐evapotranspiration feedback following multi‐decadal water table manipulation
Authors: Moore Paul A. , Pypker Thomas G. , Hribljan John A. , Chimner Rodney A. , Waddington James Michael
Published: October 2022

Northern peatlands are globally important long‐term sinks of carbon due to their predominantly saturated conditions. However, these ecosystems are expected to become drier with climate change, potentially leading to shrubification. As such, the response of the shrubification–evapotranspiration (ET) feedback may be of critical importance to future peatland energy, water and carbon dynamics. We examined the effect of multi‐decadal peatland water table (WT) alteration at three adjacent sites with increasing depth to WT (WET, INTermediate, and DRY). In order to better understand the WT–shrubification–ET feedback, we measured peatland vegetation composition, microtopography and ET partitioning, where ET was measured at the ecosystem, microform, and leaf level using eddy covariance (EC), chambers and porometry, respectively. Averaged across microforms and WT treatments, there was a difference in the median measured leaf resistance (rleaf) between plant functional types ranging from 213 s m−1 for erect dwarf shrubs, 325 s m−1 for graminoids/sedges, and 520 s m−1 for prostrate dwarf shrubs. Scaled based on LAI, the low rleaf of erect dwarf shrubs dominated hummocks, where sites with a higher proportion of hummocks had lower median canopy resistance (rv) of 141, 133 and 130 s m−1 at the WET, INT and DRY sites respectively. Nevertheless, ET was highest at the WET site and similar between the INT and DRY sites, with greater evaporation from the moss surface at the WET site. Porometry and EC data along with a three‐source model were used to independently assess the evaporative contribution from the moss surface, which ranged from 17% to 40%. For moderate and persistent changes in WT from land‐use or climate change, our results suggest vegetation succession is minimal, but the microtopographic development and the concomitant differences in LAI for the various plant functional types is key to understanding changes in total ET and partitioning.
Hydrological process controls on streamflow variability in a glacierized headwater basin
Authors: Aubry‐Wake Caroline , Pradhananga Dhiraj , Pomeroy John W.
Published: October 2022

Mountain glacierized headwaters are currently witnessing a transient shift in their hydrological and glaciological systems in response to rapid climate change. To characterize these changes, a robust understanding of the hydrological processes operating in the basin and their interactions is needed. Such an investigation was undertaken in the Peyto Glacier Research Basin, Canadian Rockies over 32 years (1988–2020). A distributed, physically based, uncalibrated glacier hydrology model was developed using the modular, object‐oriented Cold Region Hydrological Modelling Platform to simulate both on and off‐glacier high mountain processes and streamflow generation. The hydrological processes that generate streamflow from this alpine basin are characterized by substantial inter‐annual variability over the 32 years. Snowmelt runoff always provided the largest fraction of annual streamflow (44% to 89%), with smaller fractional contributions occurring in higher streamflow years. Ice melt runoff provided 10% to 45% of annual streamflow volume, with higher fractions associated with higher flow years. Both rainfall and firn melt runoff contributed less than 13% of annual streamflow. Years with high streamflow were on average 1.43°C warmer than low streamflow years, and higher streamflow years had lower seasonal snow accumulation, earlier snowmelt and higher summer rainfall than years with lower streamflow. Greater ice exposure in warmer, low snowfall (high rainfall) years led to greater streamflow generation. The understanding gained here provides insight into how future climate and increased meteorological variability may impact glacier meltwater contributions to streamflow and downstream water availability as alpine glaciers continue to retreat.
Trabectedin use in soft‐tissue sarcoma patients in a real‐world setting: Data from an Italian national drug‐access registry
Authors: Vincenzi Bruno , Napolitano Andrea , Comandone Alessandro , Sanfilippo Roberta , Celant Simone , Olimpieri Pier P. , Di Segni Susanna , Russo Pierluigi , Casali Paolo G.
Published: October 2022

Trabectedin is a marine‐derived anticancer drug approved for the treatment of patients with advanced soft‐tissue sarcomas (STS). Here, we aimed to analyze its use in a large cohort of STS patients treated in Italy in a real‐world setting. Data on STS patients treated with trabectedin in Italy were prospectively collected from January 2013 to December 2019 by the national drug regulator, the Italian Medicines Agency (AIFA). Time‐to‐off‐treatment (TToT) was defined as the time between the initial prescription of trabectedin and the date of treatment discontinuation for any cause. The impact of the different baseline covariates, including the initial prescribed dose of trabectedin, on TToT was evaluated using an accelerated failure time (AFT) models with log‐logistic distribution. In total, we analyzed data from 2633 sarcoma patients and 14 950 individual cycles of trabectedin. The median number of cycles of trabectedin received per patient was 3 (interquartile range 2‐7). The labeled 1.5 mg/sqm dose was used in 27.3% of all first prescriptions. Overall, the median TToT was 93 days. In the final AFT model, the variables significantly associated to longer TToT were female gender (+13% increase in TToT); ECOG performance status 0 (+50%); histological diagnosis of leiomyosarcoma (+22%), well‐differentiated/dedifferentiated liposarcoma (+72%) or myxoid liposarcoma (+61%); receiving treatment in a high‐volume center (+23%). In this large real‐world cohort of STS patients treated with trabectedin, our findings support the use of trabectedin in STS patients, in particular in leiomyosarcoma and liposarcoma patients, and highlight the role of treatment center volume in their management.
A functionalized separator enables dendrite‐free Zn anode via metal‐polydopamine coordination chemistry
Authors: Liu Yanfen , Liu Shude , Xie Xuesong , Li Zhicheng , Wang Pinji , Lu Bingan , Liang Shuquan , Tang Yan , Zhou Jiang
Published: October 2022

Designing a multifunctional separator with abundant ion migration paths is crucial for tuning the ion transport in rocking‐chair‐type batteries. Herein, a polydopamine‐functionalized PVDF (PVDF@PDA) nanofibrous membrane is designed to serve as a separator for aqueous zinc‐ion batteries (AZIBs). The functional groups (OH and NH) in PDA facilitate the formation of ZnO and ZnN coordination bonds with Zn ions, homogenizing the Zn‐ion flux and thus enabling dendrite‐free Zn deposition. Moreover, the PVDF@PDA separator effectively inhibits the shuttling of V‐species through the formation of VO coordination bonds. As a result, the Zn/NH4V4O10 battery with the PVDF@PDA separator exhibits enhanced cycling stability (92.3% after 1000 cycles at 5 A g−1) and rate capability compared to that using a glass fiber separator. This work provides a new avenue to design functionalized separators for high‐performance AZIBs.

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Analysis of the association between MICA gene polymorphisms and schizophrenia
Authors: Ren Xing , Mao Aiyou , Tan Shumin , Liu Jiaxiu , Wei Xiaobin
Published: October 2022

Background

The major histocompatibility complex (MHC) has been implicated in schizophrenia. This study aimed to explore the correlation between the major histocompatibility complex class I polypeptide‐related sequence A (MICA) polymorphisms and schizophrenia.

Methods

A total of 220 Han schizophrenia patients, 47 Han healthy controls, 155 Li schizophrenia patients, and 48 Li controls were selected from Hainan Province, China. The diagnosis was made according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria. Sequencing‐based‐typing (PCR‐SBT) technology was used for MICA allele typing, and the correlation analyses of MICA gene polymorphism and schizophrenia were performed.

Results

In the Han group, the three allele frequencies of MICA*002:01, MICA*A4, and MICA*A9 in the schizophrenia group were significantly higher than those in the healthy control group, and the differences were statistically significant (pc < 0.05; pc values were 0.024, 0.030, and 0.031, respectively). Yet, there was no difference in the MICA gene between the schizophrenia group and the healthy controls group in the Li population.

Conclusion

We found MICA*002:01, MICA*A4, and MICA*A9 may be susceptibility alleles for schizophrenia in the Han population, while the MICA allele polymorphism in the Li population is not associated with schizophrenia in Chinese.
Lymphoplasmacytic lymphoma and marginal zone lymphoma involving bone marrow: A diagnostic dilemma. Useful clinicopathological features to accurate the diagnosis
Authors: García‐Abellás Patricia , Ferrer Gómez Ana , Bueno Sacristán Diego , Piris Villaespesa Miguel , Talavera Yagüe María , Reguero Callejas María Eugenia , García‐Cosío Mónica
Published: October 2022

Lymphoplasmacytic lymphoma (LPL) and marginal zone lymphoma (MZL) frequently infiltrate the bone marrow
with similar histologic and immunohistochemical characteristics posing diagnostic problems. Bone marrow biopsy specimens from 25 LPL and 16 MZL have been studied, correlating with clinical, laboratory parameters and the MYD88_p.L265P mutation. Paratrabecular and interstitial infiltration pattern, serum IgM paraprotein levels, and MYD88_p.L265P mutation were significantly more frequent in LPL. Nodular or intrasinusoidal pattern with lymphocytosis and splenomegaly were associated with MZL diagnosis. Different clinical and histological parameters should be collected when LPL or MZL is suspected in bone marrow biopsy specimens.
Machine learning classification reveals robust morphometric biomarker of glial and neuronal arbors
Authors: Akram Masood A. , Wei Qi , Ascoli Giorgio A.
Published: October 2022

Neurons and glia are the two main cell classes in the nervous systems of most animals. Although functionally distinct, neurons and glia are both characterized by multiple branching arbors stemming from the cell bodies. Glial processes are generally known to form smaller trees than neuronal dendrites. However, the full extent of morphological differences between neurons and glia in multiple species and brain regions has not yet been characterized, nor is it known whether these cells can be reliably distinguished based on geometric features alone. Here, we show that multiple supervised learning algorithms deployed on a large database of morphological reconstructions can systematically classify neuronal and glial arbors with nearly perfect accuracy and precision. Moreover, we report multiple morphometric properties, both size related and size independent, that differ substantially between these cell types. In particular, we newly identify an individual morphometric measurement, Average Branch Euclidean Length that can robustly separate neurons from glia across multiple animal models, a broad diversity of experimental conditions, and anatomical areas, with the notable exception of the cerebellum. We discuss the practical utility and physiological interpretation of this discovery.
Enhancing employees' duty orientation and moral potency: Dual mechanisms linking ethical psychological climate to ethically focused proactive behaviors
Authors: Gok Kubilay , Babalola Mayowa T. , Lakshman C. , Sumanth John J. , Vo Linh Chi , Decoster Stijn , Bansal Anjali , Coşkun Ahmet
Published: October 2022

Based on social cognitive theory (SCT), we develop and test a model that links ethical psychological climate to ethically focused proactive behavior (i.e., ethical voice and ethical taking charge) via two distinct mechanisms (i.e., duty orientation and moral potency). Results from multi‐wave field studies conducted in the United States, Turkey, France, Vietnam, and India demonstrate that an ethical psychological climate indirectly influences employees' ethical voice and ethical taking charge behaviors through the dual mechanisms of duty orientation and moral potency. Additionally, we find that individuals' moral attentiveness strengthened these mediating processes. Together, these findings suggest that ethical psychological climate is an important antecedent of ethically focused proactive behavior by stimulating individuals' sense of duty and enhancing their moral potency, particularly when employees are already highly attuned to moral issues.
Do moral disengagers experience guilt following workplace misconduct? Consequences for emotional exhaustion and task performance
Authors: Ogunfowora Babatunde , Nguyen Viet Quan , Lee Clara S. , Babalola Mayowa T. , Ren Shuang
Published: October 2022

According to Bandura, moral disengagement facilitates misconduct by minimizing feelings of guilt that normally arise when one contemplates wrongdoing. While trait moral disengagement has been negatively associated with anticipatory guilt, scholars have yet to fully consider its impact on guilt post‐misconduct. In this paper, we examine the indirect effects of trait moral disengagement on post‐misconduct guilt, and downstream effects on employees' mental health and performance. Lastly, we explore the moderating role of post‐misconductstatemoral disengagement in shaping the effects of trait moral disengagement. Across three studies, we find that trait moral disengagement ispositivelylinked to guilt following interpersonal deviance, unethical work behavior, and objective cheating behavior. Further, trait moral disengagement is indirectly, positively linked to emotional exhaustion and negatively related to executive function (specifically, the capacity to inhibit distraction during tasks). In a fourth study, we find that trait moral disengagement is positively associated with guilt and subsequent emotional exhaustion when individuals employ little to no state moral disengagement immediately post‐misconduct. In contrast, trait moral disengagement is negatively linked to guilt and emotional exhaustion when individuals employ state moral disengagement post‐misconduct. We discuss the implications of these findings for advancing moral disengagement theory and research.
Managing chronic obstructive pulmonary disease in primary care: clinical characteristics of patients receiving inhaled corticosteroids
Authors: Strain Madisyn , Boehmer Kaci , Usery Justin
Published: October 2022

Background

Inhaled corticosteroid (ICS) therapy in patients with chronic obstructive pulmonary disease (COPD) has been associated with a variety of unfavourable effects, including increased risk of pneumonia, and is only recommended if specific characteristics are present to ensure patients derive the most benefit.

Aim

The primary objective was to evaluate the clinical characteristics of patients prescribed ICS therapy for COPD management in two primary care clinics at an academic medical centre. The secondary objectives were to examine provider assessment and barriers to prescribing patterns concordant with guidelines in the ambulatory care setting.

Method

A retrospective 24‐month study at two primary care clinics was undertaken at an academic medical centre in Arkansas, United States and focused on adult patients who were prescribed ICS maintenance therapy. Individuals within each clinic were identified by Classification of Diseases, Tenth Revision, Clinical Modification (ICD‐10‐CM) codes indicative of COPD from 1 January 2019 to 31 December 2020. Spirometry was also required to confirm diagnosis.

Results

Of the 189 unique patients identified, 100 were eligible for review of clinical characteristics. All patients received ICS therapy in combination with a long‐acting beta agonist (LABA) with 55% of patients also receiving a long‐acting muscarinic antagonist (LAMA). Furthermore, 32% of patients visited the emergency department or were hospitalised for a COPD exacerbation within the previous year. Approximately 47% and 36% of patients had a history of pneumonia and an eosinophil count <100 cells/mcL respectively. Barriers to guideline adherence were identified through open discussion with providers within each clinic, which included a lack of readily available resources in the clinic setting, suboptimal recognition of clinical tools within the electronic medical record and alternative guideline preferences.

Conclusion

A small portion of patients evaluated in the study were discovered to have clinical characteristics suggestive of strong ICS benefit as these therapies either lacked efficacy due to low blood eosinophil count or exacerbation rate (80% and 68% respectively), or increased the risk for harm in this population secondary to previous pneumonia diagnosis (47%).
Association of Genre of Singing and Phonotraumatic Vocal Fold Lesions in Singers
Authors: Childs Lesley F. , D'Oto Alexandra , Beams Dylan R. , Hynan Linda , Mau Ted
Published: October 2022

Objectives/Hypothesis

To determine if (1) the likelihood of presenting with phonotraumatic lesions differs by singing genre in treatment‐seeking singers and (2) if the distribution of phonotraumatic lesion types differs by singing genre.

Study Type

Retrospective.

Methods

Records of singers who presented with a voice complaint over the course of 2.5 years (June 2017–December 2019) were reviewed to determine the proportion of those with phonotraumatic lesions as a function of genre (Study 1). Separately, the lesion types and genres of singers diagnosed with phonotraumatic lesions over a 9‐year period (July 2011–March 2020) were determined (Study 2).

Results

In Study 1, 191 of 712 (26.8%) dysphonic singers were diagnosed with phonotraumatic lesions. Country/folk, gospel/jazz, and musical theater singers were more likely to present with phonotraumatic lesions. In Study 2, in 443 singers with phonotraumatic lesions, polyps and pseudocysts, but not nodules, were found to be distributed unequally across genres (χ2 p = 0.006, p < 0.0001, p = 0.064, respectively). Praise/worship singers had significantly higher proportions of polyps compared to choral singers (OR 4.8 [95% CI 1.9–12.5]) or compared to musical theater singers (OR 7.2 [95% CI 2.5–20.8]). Opera singers had significantly higher proportions of pseudocysts than choral singers (OR 3.1 [95% CI 1.5–6.1]) or musical theater singers (OR 3.7 [95% CI 1.8–7.6]).

Conclusions

The higher incidence of polyps in praise/worship singers likely reflects the more emphatic nature of singing and the tendency for acute injury. The higher incidence of pseudocysts in opera singers may reflect a more chronic nature of injury.

Level of Evidence

4 Laryngoscope, 133:1683–1689, 2023