bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic structural variation: A complex but important driver of human evolution
Authors: Soto Daniela C. , Uribe‐Salazar José M. , Shew Colin J. , Sekar Aarthi , McGinty Sean P. , Dennis Megan Y.
Published: February 2023

Structural variants (SVs)—including duplications, deletions, and inversions of DNA—can have significant genomic and functional impacts but are technically difficult to identify and assay compared with single‐nucleotide variants. With the aid of new genomic technologies, it has become clear that SVs account for significant differences across and within species. This phenomenon is particularly well‐documented for humans and other primates due to the wealth of sequence data available. In great apes, SVs affect a larger number of nucleotides than single‐nucleotide variants, with many identified SVs exhibiting population and species specificity. In this review, we highlight the importance of SVs in human evolution by (1) how they have shaped great ape genomes resulting in sensitized regions associated with traits and diseases, (2) their impact on gene functions and regulation, which subsequently has played a role in natural selection, and (3) the role of gene duplications in human brain evolution. We further discuss how to incorporate SVs in research, including the strengths and limitations of various genomic approaches. Finally, we propose future considerations in integrating existing data and biospecimens with the ever‐expanding SV compendium propelled by biotechnology advancements.
High‐Energy‐Density Graphene Hybrid Flexible Fiber Supercapacitors
Authors: Zhou Yifan , Guan Fanglan , Zhao Fangfei , Shen Yangmiao , Bao Lihong
Published: February 2023

Graphene fiber‐based supercapacitors (GFSCs) as flexible energy‐storage devices have achieved much in the wearable electronics. However, the GFSCs still suffer insufficient energy density, and of which desirable balance between mechanical and electrochemical properties has not been realized. Herein, we developed AgI and conductive polymer assisted co‐enhancement strategy to prepare the high‐performance GFSCs with super‐high energy density, favorable mechanical properties, and superior electrochemical properties. The conductive binder polymer, poly(3,4‐ethylenedioxythiophene) (PEDOT) was introduced into the GO spinning solution to enhance RGO fiber strength, conductivity, and electrochemical performance by forming a strong interface with GO in the spinning solution. On the other hand, the synergistic effect of micro‐ and nano‐scale AgI grown on the fiber surface and aqueous gel electrolyte widen the potential window of the GFSC to 1.6 V, which is much higher than that of reported GFSCs, and resulting in a significantly increased energy density. At 0.1 A cm−3, the volumetric capacitance and energy density of the fabricated GFSCs are as high as 166.6 F cm−3 and 29.65 mWh cm−3, respectively. The high strength and flexibility of the hybrid fibers endowed the GFSCs with ∼100 % capacitance retention when bent to 180°. This work opens a new way to design and fabricate high‐performance GFSCs.
The roles of ubiquitin–proteasome system and regulator of G protein signaling 4 in behavioral sensitization induced by a single morphine exposure
Authors: Wang Yanting , Hou Xingzi , Wei Shoupeng , Yan Jiaqing , Chen Zhe , Zhang Mingyu , Zhang Qingying , Lu Yingyuan , Zhang Qingjie , Zheng Tiange , Jia Jingyi , Dong Bin , Li Ying , Zhang Yuanyuan , Liang Jianhui , Li Guohui
Published: February 2023

Aims

Opioid addiction is a major public health issue, yet its underlying mechanism is still unknown. The aim of this study was to explore the roles of ubiquitin–proteasome system (UPS) and regulator of G protein signaling 4 (RGS4) in morphine‐induced behavioral sensitization, a well‐recognized animal model of opioid addiction.

Methods

We explored the characteristics of RGS4 protein expression and polyubiquitination in the development of behavioral sensitization induced by a single morphine exposure in rats, and the effect of a selective proteasome inhibitor, lactacystin (LAC), on behavioral sensitization.

Results

Polyubiquitination expression was increased in time‐dependent and dose‐related fashions during the development of behavioral sensitization, while RGS4 protein expression was not significantly changed during this phase. Stereotaxic administration of LAC into nucleus accumbens (NAc) core inhibited the establishment of behavioral sensitization.

Conclusion

UPS in NAc core is positively involved in behavioral sensitization induced by a single morphine exposure in rats. Polyubiquitination was observed during the development phase of behavioral sensitization, while RGS4 protein expression was not significantly changed, indicating that other members of RGS family might be substrate proteins in UPS‐mediated behavioral sensitization.
Comparison of the cystocholedochal angle in patients with choledocholithiasis and only cholelithiasis
Authors: Karaca Bozdağ Zekiye , Bozdağ Emre , Sonmez Suleyman , Pamukcu Beyhan Ayça , Atasever Alper
Published: February 2023

This study aims to evaluate the relation between the cystocholedochal angle (SCA) and choledocholithiasis. The data of 3.350 patients were reviewed retrospectively and a total of 628 patients who met the criteria were included in the study. The patients included in the study were divided into three groups as patients with choledocholithiasis (Group I), patients with only cholelithiasis (Group II), and patients without gallstones as control group (Group III). Measurements of SCA, cystic, bile, and common hepatic ducts (CHDs) were made on magnetic resonance cholangiopancreatography (MRCP) images. Laboratory findings and demographic characteristics of the patients were also recorded. Of the patients included in the study 64.2% were female, 35.8% were male, and their age ranged from 18 to 93 (mean 53.37 ± 18.87 years). While the mean SCA values of all patient groups were 35.44° ± 10.44°, the mean length of cystic, bile and CHDs were 28.91 ± 9.30, 40.28 ± 12.91, 27.09 ± 9.68 mm respectively. All measurements were higher in Group I in comparison to other groups, whereas all measurements of Group II were higher than those of Group III (p < 0.001). Statistical analysis suggests that a SCA of 33.5° and above is an important criterion for diagnosis of choledocholithiasis. Increase of SCA raises the likelihood of choledocholithiasis, as it facilitates the passage of stones from gallbladder into the bile ducts. This is the first study to compare SCA in patients with choledocholithiasis and those with only cholelithiasis. Therefore, we think that this study is important and will be a guide for clinical evaluation.
Prognostic analysis of three forms of Ki‐67 in patients with breast cancer with non‐pathological complete response before and after neoadjuvant systemic treatment
Authors: Zhang Weiwei , Xu Yinggang , Wang Ye , He Jinzhi , Chen Rui , Wan Xinyu , Shi Wenjie , Huang Xiaofeng , Shi Xiaoqing , Wang Jue , Zha Xiaoming
Published: February 2023

Background

Patients who do not achieve a pathological complete response (pCR) after neoadjuvant systemic treatment (NST) have a significantly worse prognosis. A reliable predictor of prognosis is required to further subdivide non‐pCR patients. To date, the prognostic role in terms of disease‐free survival (DFS) between the terminal index of Ki‐67 after surgery (Ki‐67T) and the combination of the baseline Ki‐67 at biopsy before NST (Ki‐67B) and the percentage change in Ki‐67 before and after NST (Ki‐67C) has not been compared.

Aim

This study aimed to explore the most useful form or combination of Ki‐67 that can provide prognostic information to non‐pCR patients.

Patients and Methods

We retrospectively reviewed 499 patients who were diagnosed with inoperable breast cancer between August 2013 and December 2020 and received NST with anthracycline plus taxane.

Results

Among all the patients, 335 did not achieve pCR (with a follow‐up period of ≥1 year). The median follow‐up duration was 36 months. The optimal cutoff value of Ki‐67C to predict a DFS was 30%. A significantly worse DFS was observed in patients with a low Ki‐67C (p < 0.001). In addition, the exploratory subgroup analysis showed relatively good internal consistency. Ki‐67C and Ki‐67T were considered as independent risk factors for DFS (both p < 0.001). The forecasting model combining Ki‐67B and Ki‐67C showed a significantly higher area under the curve at years 3 and 5 than Ki‐67T (p = 0.029 and p = 0.022, respectively).

Conclusions

Ki‐67C and Ki‐67T were good independent predictors of DFS, whereas Ki‐67B was a slightly inferior predictor. The combination of Ki‐67B and Ki‐67C is superior to Ki‐67T for predicting DFS, especially at longer follow‐ups. Regarding clinical application, this combination could be used as a novel indicator for predicting DFS to more clearly identify high‐risk patients.
Take care of yourself first so you can help others
Authors: Zacarese Lawrence M.
Published: February 2023

There is a reason why flight attendants instruct passengers who are traveling with young children or others needing assistance that, in case of an emergency that necessitates the oxygen masks deploying from above, they should first put their mask on before helping others. The reason is obvious; if you can't breathe due to the unexpected loss in cabin pressure, you might not be awake long enough to assist your travel companions.
Clearing your plate for more purpose‐driven work
Authors: Freebairn‐Smith Laura
Published: February 2023

In this column, I want to provide you with a practical tool that many of my clients have found helpful. This tool helps manage the barrage of demands on your time, on your organization, and on your staff — demands that often come without adequate resources. This tool can help create space for the projects that matter, in a nonaggressive way, of course.
Did court dismiss student's due process claim?
Authors: Lyerly Eric
Published: February 2023

John Doe was a member of the Bowling Green State University chapter of the Pi Kappa Alpha fraternity. In May 2021, the university charged Doe and several other Pi Kappa Alpha members with helping to cause the hazing death of a fraternity pledge two months earlier. The victim died of alcohol poisoning.
Congenital absence of left atrial appendage in a patient with ischemic stroke and atrial fibrillation
Authors: Mayire Aobuli , Jia Li Li , Yasen Nuliya , Zhou Gui‐ming , Du Xin
Published: February 2023

Left atrial appendage (LAA) is a finger‐like muscular extension of the left atrium, and it is the most prominent site for cardiac thrombus in patients with atrial fibrillation. Congenital absence of LAA could be incidentally detected in patient with ischemic stroke and atrial fibrillation. Although it is considered to be an extremely rare cardiac anomaly, its clinical significance remains unknown and there is no clear consensus in the management strategy in those patients. Therefore, we report a case of an incidentally noted congenital absence of LAA in a 68‐year‐old woman being planned for LAA closure.
Enhanced Pomegranate‐Structured SnO2 Electrocatalysts for the Electrochemical CO2 Reduction to Formate
Authors: Daele Kevin Van , Arenas‐Esteban Daniel , Choukroun Daniel , Hoekx Saskia , Rossen Alana , Daems Nick , Pant Deepak , Bals Sara , Breugelmans Tom
Published: February 2023

Although most state‐of‐the‐art Sn‐based electrocatalysts yield promising results in terms of selectivity and catalyst activity, their stability remains insufficient to date. Here, we demonstrate the successful application of the recently developed pomegranate‐structured SnO2 (Pom. SnO2) and SnO2@C (Pom. SnO2@C) nanocomposite electrocatalysts for the efficient electrochemical conversion of CO2 to formate. With an initial selectivity of 83 and 86 % towards formate and an operating potential of −0.72 V and −0.64 V vs. RHE, respectively, these pomegranate SnO2 electrocatalysts are able to compete with most of the current state‐of‐the‐art Sn‐based electrocatalysts in terms of activity and selectivity. Given the importance of electrocatalyst stability, long‐term experiments (24 h) were performed and a temporary loss in selectivity for the Pom. SnO2@C electrocatalyst was largely restored to its initial selectivity upon drying and exposure to air. Of all the used (24 h) electrocatalysts, the pomegranate SnO2@C had the highest selectivity over a time period of one hour, reaching an average recovered Faradaic efficiency (FE) of 85 %, while the commercial SnO2 and bare pomegranate SnO2 electrocatalysts reached an average of 79 and 80 % FE towards formate, respectively. Furthermore, the pomegranate structure of Pom. SnO2@C was largely preserved due to the presence of the heterogeneous carbon shell, which acts as a protective layer, physically inhibiting particle segregation/pulverisation and agglomeration.
Interactions between Hydrogen and Palladium Nanoparticles: Resolving Adsorption and Absorption Contributions
Authors: Moumaneix Lilian , Rautakorpi Akseli , Kallio Tanja
Published: February 2023

Despite the apparent simplicity of palladium hydride systems, interactions between hydrogen and palladium are multifaceted. Electrochemical hydrogen stripping allows measuring the stoichiometric coefficient of hydrogen atoms inside PdHx structures, whose properties greatly depend on x. In this paper, the insertion of H into Pd nanoparticles has been studied in a three‐electrode setup (RDE) and a proton pump cell. An original way of modelling the hydrogen desorption curve is proposed, helping in the separation of hydrogen absorption from other contributions. The loading voltage exhibits the highest impact on the H absorption into Pd, reaching Habs/Pd up to 0.47±0.02 in the RDE setup, at −0.2 VRHE. Conversely, the loading duration presents only little influence in the very first seconds. Finally, maximal Habs/Pd ratios are measured around 30–40 °C, likely due to an optimal balance between the H adsorption rate, and the H diffusion rate into Pd.
Noncovalent interactions on the electrocatalytic oxidation of ethanol on a Pt/C electrocatalyst
Authors: Han Chenjie , Lyu Yeqing , Wang Shaona , Liu Biao , Zhang Yi , Lu Jun , Du Hao
Published: February 2023

Due to their environmentally friendly nature and high energy density, direct ethanol fuel cells have attracted extensive research attention in recent decades. However, the actual Faraday efficiency of the ethanol oxidation reaction (EOR) is much lower than its theoretical value and the reaction kinetics of the EOR is sluggish due to insufficient active sites on the electrocatalyst surface. Pt/C is recognized as one of the most promising electrocatalysts for the EOR. Thus, the microscopic interfacial reaction mechanisms of the EOR on Pt/C were systematically studied in this work. In metal hydroxide solutions, hydrated alkali cations were found to bind with OHad through noncovalent interactions to form clusters and occupy the active sites on the Pt/C electrocatalyst surface, thus resulting in low Faraday efficiency and sluggish kinetics of the EOR. To reduce the negative effect of the noncovalent interactions on the EOR, a shield was made on the electrocatalyst surface using 4‐trifluoromethylphenyl, resulting in twice the EOR catalytic reactivity of Pt/C.
Photoswitchable Copper(I) and Copper(II) Complexes of Phenylazo‐3,5‐dimethylpyrazole Incorporated Ligands
Authors: Gupta Debapriya , Gaur Ankit Kumar , Thakur Sandeep Kumar , Singh Sanjay , Venkataramani Sugumar
Published: February 2023

We report the design, synthesis, characterization, and photochemistry of three photoresponsive azoheteroarene‐based neutral N‐donor ligands. Furthermore, those bidentate and tridentate ligands have been coordinated with Cu(I) and Cu(II) metal ions to form seven complexes exhibiting different geometries and nuclearities. Detailed studies of the electronic properties, photoswitching, and thermal reverse isomerization behavior of the photoswitched states of the free ligands and their metal complexes in different solvents are presented.
Interactive effects of maternal physiological arousal and regulation on maternal sensitivity: Replication and extension in an independent sample
Authors: Leerkes Esther M. , Girod Savannah A. , Buehler Cheryl , Shriver Lenka H. , Wideman Laurie
Published: February 2023

This study examined the extent to which mothers’ physiological arousal (i.e., skin conductance level [SCL] augmentation) and regulation (i.e., respiratory sinus arrhythmia [RSA] withdrawal) interacted to predict subsequent maternal sensitivity. Mothers’ (N = 176) SCL and RSA were measured prenatally during a resting baseline and while watching videos of crying infants. Maternal sensitivity was observed during a free‐play task and the still‐face paradigm when their infants were 2 months old. The results demonstrated that higher SCL augmentation but not RSA withdrawal predicted more sensitive maternal behaviors as a main effect. Additionally, SCL augmentation and RSA withdrawal interacted, such that well‐regulated maternal arousal was associated with greater maternal sensitivity at 2 months. Further, the interaction between SCL and RSA was only significant for the negative dimensions of maternal behavior used to derive the measure of maternal sensitivity (i.e., detachment and negative regard) suggesting that well‐regulated arousal is particularly important for inhibiting the tendency to engage in negative maternal behaviors. The results replicate findings from mothers in previous studies and demonstrate that the interactive effects of SCL and RSA in relation to parenting outcomes are not sample specific. Considering joint effects of physiological responding across multiple biological systems may enhance understanding of the antecedents of sensitive maternal behavior.
Transcription factors regulating vasculogenesis and angiogenesis
Authors: Payne Sophie , Neal Alice , De Val Sarah
Published: February 2023

Transcription factors (TFs) play a crucial role in regulating the dynamic and precise patterns of gene expression required for the initial specification of endothelial cells (ECs), and during endothelial growth and differentiation. While sharing many core features, ECs can be highly heterogeneous. Differential gene expression between ECs is essential to pattern the hierarchical vascular network into arteries, veins and capillaries, to drive angiogenic growth of new vessels, and to direct specialization in response to local signals. Unlike many other cell types, ECs have no single master regulator, instead relying on differing combinations of a necessarily limited repertoire of TFs to achieve tight spatial and temporal activation and repression of gene expression. Here, we will discuss the cohort of TFs known to be involved in directing gene expression during different stages of mammalian vasculogenesis and angiogenesis, with a primary focus on development.
Support for an area–heterogeneity tradeoff for biodiversity in croplands
Authors: Khan Sara , Fahrig Lenore , Martin Amanda E.
Published: February 2023

Rapid expansion of the human population poses a challenge for wildlife conservation in agricultural landscapes. One proposal for addressing this challenge is to increase biodiversity in such landscapes by increasing crop diversity. However, studies report both positive and negative effects of crop diversity on biodiversity. One possible explanation, derived from the “area–heterogeneity tradeoff hypothesis,” is that the effect of crop diversity on biodiversity depends on a tradeoff between increasing the number of crop types in a landscape and decreasing the amount of each single crop type. This should cause positive effects of increasing crop diversity at low to intermediate crop diversity and negative effects at intermediate to high crop diversity. We also propose two factors that could change the point at which the effect of increasing crop diversity shifts from positive to negative. First, we predicted that this shift would occur at a lower crop diversity when the surrounding landscape contains less semi‐natural habitat and at a higher crop diversity when the landscape contains more semi‐natural habitat. This should increase the likelihood of detecting negative effects of crop diversity when semi‐natural cover is low and positive effects when it is high. Second, we predicted that the shift from a positive to negative effect would occur at a lower crop diversity when it is measured locally than when it is measured at greater distances from the site, making detection of negative crop diversity effects more likely when measurements are at local extents. We tested these predictions using data on the biodiversity of herbaceous plants, butterflies, syrphid flies, woody plants, bees, carabid beetles, spiders, and birds at 221 crop field edges in Eastern Ontario, Canada. We found support for an area–crop diversity tradeoff. Semi‐natural cover and measurement extent influenced the biodiversity–crop diversity relationship, with positive effects when semi‐natural cover was high and negative effects when semi‐natural cover was low and when crop diversity was measured at local extents. The results suggest that policies/guidelines designed to increase crop diversity will not benefit biodiversity in the landscapes where conservation action is most urgently needed, that is, in landscapes with high agricultural use and low semi‐natural cover.
Hydrological dynamics and associated greenhouse gas fluxes in a mountain peatland under different climate scenarios
Authors: Millar David J. , Cooper David J. , Dwire Kathleen A. , Hubbard Robert M. , Ronayne Michael J. , von Fischer Joseph
Published: February 2023

Peatlands have sequestered atmospheric carbon dioxide (CO2) for millennia and can also act as significant sources of atmospheric methane (CH4). Hydrological processes that control water table dynamics, and climatic conditions such as air temperature, play important roles in mediating peatland–atmosphere exchange of these greenhouse gases. These controls are likely to be impacted by climate change, particularly for those peatlands found in cold environments, including mountain regions. In this study, we developed empirical models to simulate hydrological dynamics and ecosystem–atmosphere C exchange in a mountain peatland under three climate scenarios (2012 air temperatures, +2°C and +4°C). Observed water table dynamics and air temperature were used to model ecosystem–atmosphere C exchange during the 2012 growing season. Modelled snowmelt dynamics were used to predict water table position at the beginning of the growing season for warming scenarios, and the subsequent water table dynamics and increased air temperature were used to drive the same C exchange models during the growing seasons. Increased air temperatures led to earlier snowmelt and water table decline, causing water tables to drop by 10 and 19 cm for the +2 and +4°C scenarios, respectively. This led to roughly a two‐fold decrease in growing season net ecosystem production (NEP) in both warming scenarios, as a result of increased ecosystem respiration relative to gross primary production. Methane efflux was positively correlated with NEP and therefore decreased under the warming scenarios, albeit to a lesser degree. These results indicate that reductions in NEP and CH4 efflux are possible in low‐elevation mountain peatlands that are dependent on snowpack‐derived hydrologic inputs. These ecosystems are found at elevations where future winter precipitation will increasingly fall as rain rather than snow and melting of snowpack will occur earlier under warmer conditions.
Airway epithelial type‐2 alarmin profiles: Blood eosinophil counts remain in memory
Authors: Vernisse Charlotte , Tuaillon Edouard , Suehs Carey , Gras Delphine , Bedin Anne Sophie , Charriot Jeremy , Knabe Lucie , Vachier Isabelle , Chanez Pascal , Petit Aurélie , Bourdin Arnaud
Published: February 2023

Epithelial cytokines are involved in the orchestration of T1/T2 inflammatory patterns. We question the persistence of this trait in air–liquid interface (ALI) epithelial cultures and whether this local orientation can be related to systemic patterns (e.g., blood eosinophil counts [BECs]). We investigated alarmin release related to high versus low T2 phenotypes associated with chronic airway diseases. ALIs were reconstituted from 32 control, 40 chronic obstructive pulmonary disease, and 20 asthmatic patients. Interleukin‐8 (IL‐8; a T1‐cytokine), IL‐25, IL‐33, and thymic stromal lymphopoietin (T2‐alarmins) concentrations were assessed in subnatants at steady state and used to explain blood neutrophil and eosinophil counts. IL‐25 and IL‐8 levels were highest in asthma ALI‐subnatants, whereas IL‐33 was sparsely detected. Thymic stromal lymphopoietin levels were similar among groups. All asthma cell cultures were T1‐high/T2‐high, while chronic obstructive pulmonary disease and controls tended to be mixed. BECs were independently explained by both disease and in‐culture T2‐alarmin levels, irrespective of the T2‐alarmin considered. The epithelial ALI‐T2 signature was more frequently high in patients with a BEC > 300/mm3. Despite removal from an in vivo environment for ≥2 months, ALIs release disease‐specific cytokine “cocktails” into their subnatants, suggesting continued persistence of alarmin orientation in differentiated cell line environments.
Development of a Measure Cell to Assess by Amperometry Dissolved Oxygen in Vegetable Oils
Authors: Ben Fakhri Ahmad , Artaud Jacques , Cano Gregory , Moulin Philippe
Published: February 2023

Dissolved oxygen in vegetable oils is an important component of oil degradation over time. Various methods for the determination of dissolved oxygen in oils are proposed in the literature leading to very variable results. An amperometric method associated with a cell of measurement in dynamic mode makes it possible to determine the conditions of stability of the measurements of the relative dissolved oxygen concentration (RDOC, mg L−1) and the electrolysis current intensity (ECI) (nA) in seed oils and virgin olive oils. The effects of oxygenation/deoxygenation time and temperature on RDOC measurements are investigated. For virgin olive oils, the RDOC in bottles closed for eight weeks varies from 0 to 0.9 mg L−1. The nature of the fruitiness and the filtration of the oils have no influence on the RDOC. The monitoring of RDOC and ECI during the flow of virgin olive oil in a column open to air, simulating an industrial tank, shows differences in dissolved oxygen concentration due to a faster flow of oil in the center of the column than at the walls. This result is validated by a similar experiment with nitrogen inerting the column and by a numerical simulation.

Practical applications: Knowledge of the oxygen dissolved in vegetable oils is an important factor in limiting the autoxidation phenomenon to increase their shelf life. The development of a cell for measuring the relative dissolved oxygen concentration (RDOC) in vegetable oils and its conditions of use, provides a tool for the RDOC applicable to the different stages of the manufacturing process and during storage or packaging. The RDOC measurement is particularly useful during long storage in tanks whether inerted or not.
Analysis of the relevance of sentiment data for the prediction of excess returns in a multiasset framework
Authors: Desforges Perceval , Geissler Christophe , Liu Fei
Published: February 2023

In this study, we look at the relevance of sentiment data for the prediction of excess returns in a multiasset analysis. We start by initial exploratory data analysis in order to assess the pertinence of the sentiment data. We then compare the performance of rule‐based algorithms with and without the sentiment data. The data considered are provided by RavenPack. Finally, we explore the economic relevance of the forecast model in a long‐only and long‐short context. Inclusion of sentiment data leads to encouraging results.
Modulation of Rac1/PAK1/connexin43‐mediated ATP release from astrocytes contributes to retinal ganglion cell survival in experimental glaucoma
Authors: Zhao Guo‐Li , Zhou Hong , Guo Yun‐Hui , Zhong Shu‐Min , Zhou Han , Li Fang , Lei Bo , Wang Zhongfeng , Miao Yanying
Published: February 2023

Connexin43 (Cx43) is a major gap junction protein in glial cells. Mutations have been found in the gap‐junction alpha 1 gene encoding Cx43 in glaucomatous human retinas, suggestive of the involvement of Cx43 in the pathogenesis of glaucoma. However, how Cx43 is involved in glaucoma is still unknown. We showed that increased intraocular pressure in a glaucoma mouse model of chronic ocular hypertension (COH) downregulated Cx43, which was mainly expressed in retinal astrocytes. Astrocytes in the optic nerve head where they gather and wrap the axons (optic nerve) of retinal ganglion cells (RGCs) were activated earlier than neurons in COH retinas and the alterations in astrocytes plasticity in the optic nerve caused a reduction in Cx43 expression. A time course showed that reductions of Cx43 expression were correlated with the activation of Rac1, a member of the Rho family. Co‐immunoprecipitation assays showed that active Rac1, or the downstream signaling effector PAK1, negatively regulated Cx43 expression, Cx43 hemichannel opening and astrocyte activation. Pharmacological inhibition of Rac1 stimulated Cx43 hemichannel opening and ATP release, and astrocytes were identified to be one of the main sources of ATP. Furthermore, conditional knockout of Rac1 in astrocytes enhanced Cx43 expression and ATP release, and promoted RGC survival by upregulating the adenosine A3 receptor in RGCs. Our study provides new insight into the relationship between Cx43 and glaucoma, and suggests that regulating the interaction between astrocytes and RGCs via the Rac1/PAK1/Cx43/ATP pathway may be used as part of a therapeutic strategy for managing glaucoma.
Risk of a second cancer and infection in patients with indolent B‐cell lymphoma exposed to first‐line bendamustine plus rituximab: A retrospective analysis of an administrative claims database
Authors: Dote Satoshi , Inose Ryo , Goto Ryota , Kobayashi Yuka , Muraki Yuichi
Published: February 2023

Bendamustine has a potent immunosuppressive effect because it causes T‐cell lymphopenia, which might lead to a second primary malignancy (SPM) and would increase the risk of infection. Using the Medical Data Vision administrative claims database, we compared the cumulative incidence of SPM, infections within 6 months, and overall survival (OS) among untreated patients with indolent B‐cell lymphomas (iBCL) who received rituximab‐based chemotherapy between 2009 and 2020. Patients with grade 3b follicular lymphoma or a previous history of malignancy were excluded. Eligible 5234 patients were assigned to three cohorts: rituximab monotherapy (N = 780), RCHOP/RCVP/RTHPCOP (doxorubicin replaced with pirarubicin) (N = 2298), or bendamustine/rituximab (BR) (N = 2156). There were 589 recorded SPMs, of which myelodysplastic syndromes were the most common (1.7%). The cumulative incidence of SPM was significantly higher in patients treated with BR than in those treated with rituximab monotherapy (p < 0.01) or RCHOP/RCVP/RTHPCOP (p < 0.0001): the 5‐year cumulative incidence function was 18.1%, 12.5%, and 12.9%, respectively. In the Fine‐Gray subdistribution hazards model, BR showed a significantly higher cumulative incidence of SPM than RCHOP/RCVP/RTHPCOP (subhazard ratio, 1.33; 95% confidence interval [CI], 1.10–1.61). Furthermore, in sensitivity analysis, a nested case‐control study using an entire cohort showed consistent results: the SPM odds ratios (95% CI) of first‐line bendamustine, bendamustine after first‐line, and any‐line bendamustine were 1.43 (1.14–1.78), 1.26 (0.96–1.64), and 1.33 (1.09–1.62), respectively. Regarding infections, adjusted odds ratios (95% CI) of BR compared to RCHOP/RCVP/RTHPCOP were as follows: cytomegalovirus infection, 13.7 (4.88–38.4); bacterial pneumonia, 0.63 (0.50–0.78); and pneumocystis pneumonia, 0.24 (0.11–0.53). There was no significant difference in OS between RCHOP/RCVP/RTHPCOP and BR in patients with follicular, mantle cell, marginal zone, or lymphoplasmacytic lymphomas. In conclusion, treatment strategies that consider the risk of SPM and infections after chemotherapy are warranted in patients with iBCL.
Evaluation of the quality of clinical guidelines for prophylaxis of venous thromboembolism in urological surgeries by the AGREE II review instrument
Authors: Shakiba Behnam , Kabir Ali , Irani Shirin , Torabi Nasim , Nourmohamad Vahid , Farid Mohaddese
Published: February 2023

Background and Aims

Venous thromboembolism (VTE) is the most common cause of death during the first 30 days after surgery. There is not any study which critically evaluated clinical guidelines related to VTE prophylaxis in urological surgeries. Therefore, in this study, we decided to evaluate related clinical guidelines using the AGREE II instrument to take a positive step towards improving the care of these patients.

Methods

The latest version of all available clinical guidelines related to the topic of VTE prophylaxis in urological surgeries until 2021 was searched. Four appraisers, including one urologist, one cardiologist, one epidemiologist, and one MD who had prior knowledge of working with the AGREE II tool and international articles in this field appraised selected clinical guidelines. Using the AGREE II review tool, clinical guidelines were critically evaluated. Then, the score of six domains of AGREE II for each guideline was calculated and compared with each other, and the relationship between the domains was measured by Kendall's correlation test. To determine the reliability of the test, interclass correlation coefficients were calculated for all indicators.

Results

Items were rated on a 7‐point scale from 1 (strongly disagree) to 7 (strongly agree). NICE, CHEST, and EAU guidelines obtained the highest scores from the Overall Assessment criteria by scoring 6, 5.75, and 5.25, respectively. There was only a correlation between the score of Overall Assessment criterion with “Applicability” domain, with Kendall's correlation coefficient of 0.867 and p = 0.015. The domains of “Clarity and presentation” and “Scope and purpose” obtained the highest standardized scores by getting 84.49% and 75.69%, respectively, and “Applicability” with 30.04% obtained the lowest standardized score.

Conclusion

In this study, NICE, CHEST, and EAU guidelines are suggested as clinical guidelines by obtaining the highest scores from Overall Assessment criterion.
Comparative study of clinical symptoms of chronic rhinosinusitis with nasal polyps patients
Authors: Hu Jingmin , Wang Le , Ma Ruixia
Published: February 2023

Aim

The aim of this study is to explore the clinical characteristics in chronic rhinosinusitis with nasal polyps (CRSwNP) patients with different serum specific IgE (SIgE) and eosinophilic granulocyte infiltration status.

Methods

This retrospective observational study included patients diagnosed with CRSwNP and underwent functional endoscopic sinus surgery at the Yinchuan First People's Hospital between June 2019 and June 2021. A total of 192 patients with CRSwNP were included (100 males). The patients were 41.7 ± 15.1 years old. The disease course ranged 4.6–18.2 months. The visual analog scale (VAS) score (p < .001), endoscopic score (p = .014), computerized tomography (CT) score (p < .00) and the sino‐nasal outcome Test‐22 (SNOT‐22) score (p < .001) were significantly different among patients with SIgE‐positive combined eosinophilic chronic rhinosinusitis (ECRS), patients with SIgE‐positive combined non‐ECRS, patients with SIgE‐negative combined ECRS, and patients with SIgE‐negative combined non‐ECRS.

Results

In pairwise comparison, the VAS score (20.72 ± 2.24 vs. 13.09 ± 1.62, 13.84 ± 1.34, and 12.67 ± 1.20, respectively), endoscopic score (8.09 ± 1.04 vs. 7.06 ± 0.98, 7.69 ± 1.18, and 7.75 ± 1.07, respectively), CT score (13.18 ± 1.66 vs. 8.79 ± 0.88, 11.08 ± 1.12, and 11.08 ± 1.12, respectively), and SNOT‐22 score (27.62 ± 2.31 vs. 12.09 ± 1.83, 14.84 ± 1.84, and 12.97 ± 1.50, respectively) was significantly higher in patients with SIgE‐positive combined ECRS compared to patients with SIgE‐positive combined non‐ECRS, patients with SIgE‐positive combined non‐ECRS (all p < .0083). The VAS score, endoscopic score, and CT score might be higher in CRSwNP patients with SIgE‐positive combined ECRS.

Conclusion

In this study, the VAS score, endoscopic score, and CT score were higher in the patients with SIgE‐positive combined ECRS. This study might provide a reference for treatment in patients with CRSwNP.
Viral load of SARS‐CoV‐2 Omicron BA.5 is lower than that of BA.2 despite the higher infectivity of BA.5
Authors: Takatsuki Yuna , Takahashi Yuta , Nakajima Jun , Iwasaki Yumi , Nagano Katsutoshi , Tani‐Sassa Chihiro , Yuasa Sonoka , Kanehira Saki , Sonobe Kazunari , Nukui Yoko , Takeuchi Hiroaki , Tanimoto Kousuke , Tanaka Yukie , Kimura Akinori , Ichimura Naoya , Tohda Shuji
Published: February 2023

Background

Sublineage BA.5 of the SARS‐CoV‐2 Omicron variant rapidly spread and replaced BA.2 in July 2022 in Tokyo. A high viral load can be a possible cause of high transmissibility.

Methods and Results

The copy numbers of SARS‐CoV‐2 in nasopharyngeal swab samples obtained from all patients visiting the hospital where this research was conducted were measured using reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR). Viral genotypes were determined using PCR‐based melting curve analysis. Next, whole‐genome sequencing was performed using approximately one fifth of the samples to verify the viral genotypes determined using PCR. Then, the copy numbers of the BA.1, BA.2, and BA.5 cases were compared. Contrary to expectations, the copy numbers of the BA.5 cases (median 4.7 × 104 copies/μL, n = 291) were significantly (p = .001) lower than those of BA.2 cases (median 1.1 × 105 copies/μL, n = 184). There was no significant difference (p = .44) between the BA.5 and BA.1 cases (median, 3.3 × 104 copies/μL; n = 215). Conclusion: The results presented here suggest that the increased infectivity of BA.5 is not caused by higher viral loads, but presumably by other factors such as increased affinity to human cell receptors or immune escape due to its L452R mutation.
Melatonin reduces IL‐33 and TSLP expression in human nasal epithelial cells by scavenging ROS directly
Authors: Gong Min‐jie , Zhang Hai‐bao , Lou Miao , Wang Yu‐sheng , Ma Rui‐ping , Hu Zhen‐zhen , Zheng Guo‐xi , Zhang Ya
Published: February 2023

Background

Chronic rhinosinusitis (CRS) is a chronic mucosal inflammation of the nasal cavity and sinuses. It is classified into CRS without nasal polyps and CRS with nasal polyps (CRSwNP). CRSwNP has high recurrence, especially CRSwNP with massive eosinophil infiltration which is mediated by type 2 inflammatory response. Melatonin is a hormone secreted by the pineal gland, it has powerful antioxidant and anti‐inflammatory effects in addition to regulating biological rhythms. There are no studies on melatonin for the treatment of CRS, so we aimed to explore whether melatonin could be used for the treatment of CRS.

Materials and Methods

In this study, we used melatonin to treat a cell model of CRS. Subsequently, MTT assay was performed to examine the cell viability of human nasal epithelial cells (HNEpCs), a reactive oxygen species (ROS) kit to detect ROS production, a malondialdehyde (MDA) kit to detect the MDA content in the cell culture supernatant, and an apoptosis kit and Western blot analysis to detect apoptosis. The expressions of Nrf2, HO‐1, IL‐33, TSLP, and IL‐25 were detected by Western blot analysis.

Results

Melatonin improved the viability of HNEpCs, reduced lipopolysaccharide‐induced ROS, reduced the MDA content, and inhibited their apoptosis. More importantly, melatonin reduced the expression of IL‐33 and TSLP, an important phenomenon for the treatment of CRSwNP.

Conclusion

Melatonin protects HNEpCs from damage in inflammation and reduces IL‐33 and TSLP expression of HNEpCs.
Lived experiences of utilizing cultural resiliency to navigate traumatic loss
Authors: Tyler Jessica Meléndez , Darrow Nancy E. Thacker , Outlaw Aisha B. , Guffin Jennifer P.
Published: February 2023

Extensive literature focuses on grief and loss and individual levels of resiliency, while less research has been done on cultural resiliency. This phenomenological study examined the lived experiences of using cultural resiliency to cope with traumatic loss in 2020. Compounded grief experiences and effects, emotional impacts, learned resiliency, cultural protective factors, and therapy experiences emerged as themes from these narratives. Implications for the field are provided to expand our thinking about ways to decolonize counseling.
Helicobacter pylori‐derived outer membrane vesicles contribute to Alzheimer's disease pathogenesis via C3‐C3aR signalling
Authors: Xie Junhua , Cools Lien , Van Imschoot Griet , Van Wonterghem Elien , Pauwels Marie J. , Vlaeminck Ine , De Witte Chloë , EL Andaloussi Samir , Wierda Keimpe , De Groef Lies , Haesebrouck Freddy , Van Hoecke Lien , Vandenbroucke Roosmarijn E.
Published: February 2023

The gut microbiota represents a diverse and dynamic population of microorganisms that can influence the health of the host. Increasing evidence supports the role of the gut microbiota as a key player in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Unfortunately, the mechanisms behind the interplay between gut pathogens and AD are still elusive. It is known that bacteria‐derived outer membrane vesicles (OMVs) act as natural carriers of virulence factors that are central players in the pathogenesis of the bacteria. Helicobacter pylori (H. pylori) is a common gastric pathogen and H. pylori infection has been associated with an increased risk to develop AD. Here, we are the first to shed light on the role of OMVs derived from H. pylori on the brain in healthy conditions and on disease pathology in the case of AD. Our results reveal that H. pylori OMVs can cross the biological barriers, eventually reaching the brain. Once in the brain, these OMVs are taken up by astrocytes, which induce activation of glial cells and neuronal dysfunction, ultimately leading to exacerbated amyloid‐β pathology and cognitive decline. Mechanistically, we identified a critical role for the complement component 3 (C3)‐C3a receptor (C3aR) signalling in mediating the interaction between astrocytes, microglia and neurons upon the presence of gut H. pylori OMVs. Taken together, our study reveals that H. pylori has a detrimental effect on brain functionality and accelerates AD development via OMVs and C3‐C3aR signalling.
A cost‐effective DC microgrid system for resilient power supply to grid‐connected societies
Authors: Kumar Jaynendra , Agarwal Anshul , Singh Nitin
Published: February 2023

Local renewable energy sources have the potential to provide power security to societies. The main objective of this research is to improve electricity reliability in grid‐connected societies in case of the grid failure or during blackouts. Here, a cost‐effective method to utilize local irregular renewable energy sources for community applications has been proposed. Solar PV, pumping units, domestic loads, and pico hydro are the main parts of the proposed system. The storage water tank also performs the function of pump storage to deliver power during off‐sun periods. The pump storage generates electricity by using the unused potential of the water stored in the storage tank. In islanded mode, the system delivers power to the village to essential loads and fluctuating power to the dump load. The paper provides a case study in which the proposed DC microgrid has been demonstrated for a society to validate the system's performance for different practical scenarios. It has been validated for financial and technical feasibility through economic analysis and MATLAB Simulation performance respectively.
Strain distribution in the bursal rotator cuff based on whole‐muscle and muscle subregion‐specific loading: A cadaveric study
Authors: Yuri Takuma , Prado Maria , Trevino Jose H. , Giambini Hugo
Published: February 2023

Rotator cuff (RC) tears are common injuries leading to significant dysfunction of the shoulder. Rotator cuff tears alter tension and strain in muscles and tendons. Anatomical studies demonstrated that rotator cuff muscles are comprised of anatomical subregions. However, the strain distribution within the rotator cuff tendons generated from the tension from each anatomical subregion is unknown. We hypothesized that subregions would present distinct 3‐dimensional (3D) strain distributions within the rotator cuff tendons, and that the anatomical insertion configuration of the supraspinatus (SSP) and infraspinatus (ISP) tendons might dictate strain, thus tension, transmission. 3D‐strains in the bursal side of the SSP and ISP tendons of eight fresh‐frozen cadaveric intact shoulders were obtained by applying tension on the whole SSP and ISP muscles, and on their subregions using an MTS system. Strains in the anterior region of the SSP tendon were higher than in the posterior region with whole‐SSP anterior‐region (p < 0.05) and whole‐SSP muscle loading. Higher strains were observed in the inferior half of the ISP tendon with whole‐ISP muscle (p < 0.05), middle‐subregion (p < 0.01), and superior‐subregion (p < 0.05) loading. Tension generating from the posterior‐region of the SSP was primarily transmitted to the middle facet via an overlap between the SSP and ISP tendons insertions, while the anterior‐region mainly distributed its tension into the superior facet. Tension generating from the middle and superior‐regions of the ISP was distributed into the inferior portion of the ISP tendon. These results emphasize the importance of the distinct anatomical subregions of the SSP and ISP muscles in distributing the tension to the tendons.
Tendon cell and tissue culture: Perspectives and recommendations
Authors: Szczesny Spencer E. , Corr David T.
Published: February 2023

The wide variety of cell and tissue culture systems used to study and engineer tendons can make it difficult to choose the best approach and “optimal” culture conditions to test a given hypothesis. Therefore, a breakout session was organized at the 2022 ORS Tendon Section Meeting that focused on establishing a set of guidelines for conducting cell and tissue culture studies of tendon. This paper summarizes the outcomes of that discussion and presents recommendations for future studies. In the case of studying tendon cell behavior, cell and tissue culture systems are reductionist models in which the culture conditions should be strictly defined to approximate the in vivo condition as closely as possible. In contrast, for tissue engineering tendon replacements, the culture conditions do not need to replicate native tendon, but the outcome measures for success should be narrowly defined for the specific clinical application. Common recommendations for both applications are that researchers should perform a baseline phenotypic characterization of the cells that are ultimately used for experimentation. For models of tendon cell behavior, culture conditions should be well justified by existing literature and meticulously reported, tissue explant viability should be assessed, and comparisons to in vivo conditions should be made to determine baseline physiological relevance. For tissue engineering applications, the functional/structural/compositional outcome targets should be defined by the specific tendons they seek to replace, with key biologic and material properties prioritized for construct assessment. Lastly, when engineering tendon replacements, researchers should utilize clinically approved cGMP materials to facilitate clinical translation.