bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis of cancer in the Emergency Department: A scoping review
Authors: Delamare Fauvel Alix , Bischof Jason J. , Reinbolt Raquel E. , Weihing Veronica K. , Boyer Edward W. , Caterino Jeffrey M. , Wang Henry E.
Published: January 2023

Background

The Emergency Department (ED) plays a key role in the identification and care of acute medical conditions, including cancer. In this scoping review, we aimed to determine the role of the ED in the acute diagnosis of cancer.

Methods

We conducted a scoping review of articles according to Preferred Reporting Items for Systematic Review and Meta‐Analyses (PRISMA) using PubMed and Google Scholar. We screened studies of adults with a new diagnosis of cancer in the ED. We included randomized control trials, prospective, retrospective, and cross‐sectional observational studies, and case reports published in English since 2000. We grouped the articles into categories based on their objectives and findings.

Results

Of the 4459 articles, we included 47 in the review. The identified studies fell into three major categories: (1) studies describing the incidental diagnosis of cancer in the ED (n = 11, 23%), (2) studies characterizing the acute initial presentation of cancer in the ED (n = 19, 41%), and (3) studies describing the ED as a pathway to cancer diagnosis in the healthcare system (n = 17, 36%). Across the studies, cancer diagnoses in the ED were more likely in patients with higher comorbidities, occurred at later stages, and resulted in worse survival rates.

Conclusions

The ED plays a prominent role in the initial diagnosis of cancer. Efforts must be made to integrate the ED within the cancer care continuum.
Prognostic value of modified criteria for hydroxyurea resistance or intolerance in patients with high‐risk essential thrombocythemia
Authors: Park Young Hoon , Lee Sewon , Mun Yeung‐Chul , Park Dong Jin
Published: January 2023

Background

Recognizing intolerance or resistance to hydroxyurea (HU), which is related to the high risk of a disease transformation and reduced survival in essential thrombocythemia (ET), is crucial to making a reasonable decision about second‐line therapy. We assessed the prognostic impact of the modified European LeukemiaNet (mELN) criteria used in a recent MAJIC‐ET trial by analyzing the incidence of resistance or intolerance to HU and the survival outcome compared with those of the ELN criteria.

Methods

We retrospectively compared the development of HU resistance or intolerance according to the ELN and mELN criteria for 148 high‐risk ET patients receiving HU between 2014 and 2018. The maximum tolerated dose for defining HU resistance was used in the mELN criteria.

Results

The median age of patients was 65 years (range, 36–87), with a median follow‐up of 3.6 years (range, 1.1–6.4). Two thromboembolic events were observed during HU treatment. When applying the ELN criteria, 10 patients (6.9%) were resistant (n = 5 [3.4%]) or intolerant (n = 5 [3.4%]) to HU in comparison with 22 patients (15%, 14 [9.8%]) resistant and 8 [5.5%] intolerant when applying the mELN criteria. Transformation to myelofibrosis and acute myeloid leukemia occurred in 2 (1.4%) patients and 1 (0.7%) patient, respectively, as defined by the ELN criteria compared with 3 (2.1%) and 2 (1.4%) patients as defined by the mELN criteria. In multivariate analysis of transformation‐free survival, HU resistance defined by the mELN criteria but not the ELN criteria was an independent prognostic factor. In addition, HU resistance as defined by both sets of criteria was an independent risk factor for inferior overall survival. Intolerance of HU did not have any prognostic impact on survival.

Conclusions

The mELN criteria are useful for identifying high‐risk ET patients who might be eligible for second‐line therapy in practice, which should be validated in a prospective setting.
Pan‐cancer molecular analysis of EGFR large fragment deletion in the Asian population
Authors: Pu Jun , Guo Huannan , Yu Ruoying , Ou Qiuxiang , Bao Hua , Wu Xue , Tang Sanyuan , Chang Qingyong
Published: January 2023

Background

Large fragment deletion (LFD) of EGFR was associated with carcinogenesis in many types of cancers. However, the molecular features of EGFR‐LFD have not been studied in the Asian cancer population.

Method

Here we retrospectively analyzed the targeted sequencing data from a large cancer database.

Results

EGFR‐LFD was detected at a frequency of 0.03% with EGFRvIII being the most frequently observed LFD. TERTp variants were identified in 60% of the cases. TP53 alterations (33%) were mutually exclusive with TERTp variants and coexisted with EGFR‐LFD in lung cancer and colorectal cancer. EGFR amplification (67%) and chromosome 10p deletion (53%) were the most focal‐level and arm‐level CNV in this cohort. EGFR exon2–17 skipping was found in the tumor tissue of one patient after progressing on osimertinib.

Conclusion

Our study provided valuable insights into the distribution and molecular characteristics of EGFR‐LFD, hoping to shed light on the treatment management for EGFR‐LFD carriers.
Pasting properties, baking quality, and starch digestibility of einkorn, emmer, spelt, and hard red spring wheat
Authors: Kulathunga Jayani , Simsek Senay
Published: January 2023

Background and Objectives

Hulled wheat species have been recognized as interesting raw materials to produce niche products. More research studies are necessary on the hulled wheat species' quality, processability, and functional and nutritional properties to develop novel food products. This study was conducted to evaluate the pasting properties, baking quality, and in vitro starch digestibility of hulled wheat species.

Findings

Significantly (p < .05) higher peak viscosity values were observed in spelt, while significantly (p < .05) higher final viscosity values were observed in einkorn. Results of the baking quality revealed that there are potential genotypes of spelt that can be used to make specialty bread with similar loaf characteristics as hard red spring wheat. Significantly (p < .05) higher slowly digestible starch content was found in einkorn, emmer, and spelt compared to hard red spring wheat.

Conclusions

Einkorn, emmer, and spelt used in this study, differ from hard red spring wheat in terms of dough properties, baking quality, starch digestibility, and pasting properties.

Significance and Novelty

The results of this study made a detailed comparison between hulled wheat and modern bread wheat grown in North Dakota, therefore, results would be useful in breeding to develop and release new and improved lines of hulled wheat species.
A comprehensive overview of the electrochemical mechanisms in emerging alkali metal–carbon dioxide batteries
Authors: Lin Jiangfeng , Song Wanqing , Xiao Caixia , Ding Jingnan , Huang Zechuan , Zhong Cheng , Ding Jia , Hu Wenbin
Published: January 2023

Alkali metal–carbon dioxide (Li/Na/K‐CO2) batteries are emerging electrochemical energy storage technologies in the context of the energy crisis and the urgent demand for carbon neutrality. Alkali metal–CO2batteries offer a new strategy for CO2fixation and utilization, and thus has been receiving considerable attention in recent years. Considerable progress has been achieved since alkali metal–CO2batteries were invented, especially in terms of development of new electrode materials, and yet, research is lacking on the underlying mechanisms of the systems. This is the first typical review focusing on the electrochemical mechanisms of metal–CO2batteries that summarizes the current understanding of and provides insights into the thermodynamic reaction pathways, the kinetic characteristics, and the crucial factors determining the reaction mechanisms in alkali metal–CO2batteries. The review starts with the fundamental concepts of alkali metal–CO2batteries, followed by a comprehensive discussion of the working mechanisms on cathodes and anodes. Moreover, the operation mechanisms of state‐of‐the‐art electrolytes, including liquid and (quasi‐)solid‐state electrolytes, are also described. Finally, we identify the unsolved problems in current alkali metal–CO2batteries and propose potential topics for future research.
Structurally Diverse Diterpenoids from the Sanya Bay Nudibranch Hexabranchus sanguineus and Its Sponge‐Prey Chelonaplysilla sp.
Authors: Shen Shou‐Mao , Li Song‐Wei , Su Ming‐Zhi , Yao Li‐Gong , Appendino Giovanni , Guo Yue‐Wei
Published: January 2023

Investigation of the South China Sea nudibranch Hexabranchus sanguineus from Sanya Bay afforded, in addition to three known compounds, nine new diterpenoids of the 5,19‐cycloclerodane‐ (sanyanolides A–D), clerodane‐ (sanyanolide E) and subersin‐ (sanyanolides F–I) type. Remarkably, six diterpenoids aforementioned from H. sanguineus were also isolated from the sponge Chelonaplysilla sp. from the same water region, suggesting a trophic relationship between H. sanguineus and Chelonaplysilla sp. The structure and absolute configuration of new compounds were established by a combination of spectroscopic data, X‐ray diffraction analysis and/or time‐dependent density functional theory/electronic circular dichroism calculations. A plausible biogenetic relationship between these diterpenoids, along with the chemo‐ecological implications of their co‐occurrence in the two organisms investigated, was proposed and discussed. In in vitro bioassays, echinoclerodane A exhibited a potent inhibitory effect (IC50=2.81 μM) on LPS‐induced inflammatory response in RAW 264.7 macrophage cells. In addition, echinoclerodane A and oculatolide showed considerable antibacterial activities with MIC values ranging from 1.0 to 8.0 μg/mL.
Iridium‐Catalyzed 1,3‐Rearrangement of Allylic Alcohols
Authors: Li Fei , Luo Yicong , Zhu Xuejie , Ye Yong , Yuan Qianjia , Zhang Wanbin
Published: January 2023

The allylic alcohol structural motif is prevalent in many important molecules and valuable building blocks. The rearrangement reaction is one of the most important transformations, however there are only a few reports for the 1,3‐rearrangement of allylic alcohols. Herein, a 1,3‐rearrangement of allylic alcohols catalyzed by an Ir(III) dihydride complex is described. This reaction could provide the corresponding less accessible allylic alcohols regio‐ and stereoselectively from readily available E/Z mixtures of the substrates. Furthermore, a tandem alkene isomerization followed by 1,3‐rearrangement of homoallylic alcohols was also realized. In addition, this rearrangement reaction could be used to synthesize the natural product Navenone B. Mechanistic investigation indicated that the reaction pathway involved a π‐allyl‐Ir(V) intermediate and that the dihydride in the iridium catalyst acts as a hydrogen switch to modulate the valence of the iridium center.
Quinoline Hydrazide/Hydrazone Derivatives: Recent Insights on Antibacterial Activity and Mechanism of Action
Authors: Verma Sangeeta , Lal Sukhbir , Narang Rakesh , Sudhakar Kalvatala
Published: January 2023

Antibiotics are becoming gradually ineffective due to drug resistance, leading to greater difficulty in the treatment of infectious diseases. Therefore, the development of new chemical entities with different mechanisms of action is essential in the fight against resistant microorganisms. Various studies have shown that quinoline hydrazide/hydrazone derivatives possess several biological activities, such as antimalarial, antitubercular, anticancer, anti‐inflammatory, and antimicrobial. Among these activities, the antibacterial activity of quinoline hydrazide/hydrazone derivatives is noteworthy. The synthetic flexibility of the quinoline ring has led to the development of a wide range of structurally diverse quinoline hydrazide/hydrazone derivatives, which can act at various bacterial targets such as DNA gyrase, glucosamine‐6‐phosphate synthase, enoyl ACP reductase, and 3‐ketoacyl ACP reductase. This review emphasizes the antibacterial potential of various reported quinoline hydrazide/hydrazone derivatives based on substitution in the quinoline ring. The antibacterial activity of various metal‐quinoline hydrazide/hydrazone complexes is also discussed. The aim of this review is to assemble and scrutinize the latest reports in this promising area of drug development.
Emerging photo‐integrated rechargeable aqueous zinc‐ion batteries and capacitors toward direct solar energy conversion and storage
Authors: Wang Kexuan , Li Heng , Xu Zhu , Wang Huibo , Ge Mingzheng , Zhang Yanyan , Chen Shi , Tang Yuxin
Published: January 2023

Photo‐integrated rechargeable aqueous zinc‐ion batteries (ZIBs)/zinc‐ion capacitors (ZICs) have recently attracted substantial attention as a viable strategy to realize solar to electrochemical energy conversion and storage in a single device. Herein, a timely perspective on the latest advances in photo‐integrated rechargeable ZIBs/ZICs is presented. We first provide a brief introduction for the three different device types and working principles of the photo‐integrated rechargeable ZIB/ZIC devices, including tandem connected photo‐rechargeable hybrid energy systems, photo‐electrode integrated ZIBs, and photo‐rechargeable ZIBs/ZICs. Then, the significant advances in configuration design, materials chemistry, and performance evaluation of photo‐integrated rechargeable ZIBs/ZICs are systematically discussed. At last, the current challenges and future research emphases are suggested, which is to pave the way for the photo‐integrated rechargeable ZIBs/ZICs from laboratory technology to commercialization. This short yet informative perspective aims to evoke more research interests in developing high‐performance photo‐integrated rechargeable ZIBs/ZICs and other hybrid energy systems toward the direct conversion and storage of solar energy to electrochemical energy.
Synergy of Pt Single Atom and Clusters toward Selective Glycerol Oxidation
Authors: Luo Zhicheng , Zhu Zhiguo , Xiao Rui , Chu Dawang
Published: January 2023

Selective oxidation of excess glycerol to glyceric acid is a significant reaction but the reaction is inhibited by the C−H activation that has a high energy barrier. Here, we introduced Pt single atom species (Pt−O−Ce) into Pt/CeO2, which gave a high glycerol conversion of 90.9% with a high glyceric acid selectivity of 83.2% under the mild reaction conditions (T=100 °C, O2 flow of 5 mL min−1, and non‐alkaline). The C−H bond can be easily adsorbed and activated over Pt−O−Ce, which facilitated the selective oxidation of primary C−OH with a bidentate adsorption on Ptcluster, verified by the CO‐DRIFT, XPS, HRTEM, and in situ IR adsorption experiments. This synergy provided a way to design stable and active catalyst in biomass conversion.
Relative Bioavailability and Food Effect of Asciminib Pediatric Mini‐tablet Formulation Compared to the Reference Tablet Formulation in Healthy Adult Participants
Authors: Hoch Matthias , Bebrevska Lidiya , Singh Namrata , Hourcade‐Potelleret Florence
Published: January 2023

Asciminib, a first‐in‐class allosteric BCR::ABL1 inhibitor that works by Specifically Targeting the ABL Myristoyl Pocket (STAMP) is used in the treatment of chronic myeloid leukemia. We describe a randomized, single‐dose, open‐label, four‐period crossover study in healthy adult participants (N = 24) which evaluated the relative bioavailability of a single 40‐mg dose of asciminib in pediatric formulation (1‐mg mini‐tablets) compared with the reference adult tablet under fasted conditions. Additionally, the effect of food on the bioavailability of the mini‐tablet formulation was evaluated. Under fasted conditions, asciminib exposure was similar for both formulations (geometric mean [Gmean] area under the concentration–time curve from time 0 to infinity [AUCinf] 5970 and 5700 ng ×h/mL, respectively). Food decreased the AUCinf and maximum plasma concentration (Cmax) of the asciminib mini‐tablets; this effect was more pronounced with a high‐fat meal (Gmean ratios [90% confidence interval]: fasted/low‐fat meal, 0.42 [0.38–047], 0.32 [0.28–0.37], respectively; fasted/high‐fat meal, 0.30 [0.27–0.34], 0.22 [0.19–0.25], respectively). The mini‐tablets were assessed to be easy to ingest with good palatability. Asciminib doses for a pivotal pediatric clinical trial will be defined using physiologically based pharmacokinetic modeling, which will consider the age and the higher food effect observed with the mini‐tablets.
Predicting Treatment Responses in Patients With Osteoarthritis: Results From Two Phase III Tanezumab Randomized Clinical Trials
Authors: Colloca Luana , Dworkin Robert H. , Farrar John T. , Tive Leslie , Yang Jiyue , Viktrup Lars , Dasic Gorana , West Christine R. , Whalen Ed , Brown Mark T. , Gilbert Steven A. , Verburg Kenneth M.
Published: January 2023

Prediction of treatment responses is essential to move forward translational science. Our question was to identify patient‐based variables that predicted responses to treatments. We conducted secondary analyses on pooled data from two randomized phase III clinical trials (NCT02697773 and NCT02709486) conducted in participants with moderate to severe osteoarthritis randomized to subcutaneous placebo (n = 514) or tanezumab 2.5 mg (n = 514). We used gradient boosted regression trees to identify variables that predicted Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain subscale scores at Week 16 and marginal plots to determine the directional relationship between each variable category and responses to placebo or tanezumab within the models. We also used Virtual Twins models to identify potential subgroups of response to the active treatment vs. placebo. We found that responses to placebo were predicted by baseline WOMAC Physical Function, baseline WOMAC Pain, the radiographic classification of the index joint, and the standard deviation of diary pain scores at baseline. In contrast, baseline WOMAC Pain along with failure of prior medications, duration of disease, and standard deviation of diary pain scores at baseline were predictive of tanezumab responses as expressed by the WOMAC Pain scores at Week 16. Those who responded to tanezumab vs. placebo were identified based on the radiographic classification of the index joint and either age or smoking status. These secondary‐data analyses identified distinct and common patient‐based variables to predict response to placebo or tanezumab. These findings will inform the design of future clinical trials, helping to move forward clinical pharmacology and translational science.
Long‐distance and anti‐disturbance wireless power transfer based on concentric three‐coil resonator and inhomogeneous electromagnetic metamaterials
Authors: An Huilin , Yuan Jian , Li Jun , Cao Liqiang
Published: January 2023

For wireless power transfer system (WPTS), the deflection of the resonant coil and the increase of the transmission distance will cause a sharp decline in transmission efficiency. This paper presents a novel long‐distance and anti‐deflection wireless power transfer based on concentric three‐coil resonator and inhomogeneous electromagnetic metamaterials (IEM). First, the effective receiving area of the resonator is analyzed, and the anti‐disturbance concentric three‐coil resonator is designed quantitatively. Considering the magnetic field distribution generated by the transmitting coil, this paper proposes and designs IEM with three kinds of effective permeability, which is applied in different design area, respectively. Meanwhile, the finite‐element‐method simulation proves an improvement in magnetic field modulation and flux leakage control when WPTS with IEM is used. The experimental results show that, compared with the traditional one‐coil to one‐coil, the WPTS designed in this paper achieves an increase of 43% in the efficiency at a 90° deflection. Furthermore, the efficiency of WPTS with IEM is 17% and 7% higher than that of WPTS with homogeneous electromagnetic metamaterials (HEM) and without electromagnetic metamaterials. As a result, the design method in this paper can improve the anti‐disturbance capability and increase the transmission distance and efficiency.
PDE4 inhibitor Roflumilast modulates inflammation and lipid accumulation in PCOS mice to improve ovarian function and reduce DHEA‐induced granulosa cell apoptosis in vitro
Authors: Ji Xiaowei , Ye Yao , Wang Lin , Liu Suying , Dong Xi
Published: January 2023

This study was implemented to address the role of Roflumilast in polycystic ovary syndrome (PCOS) as well as to discuss its reaction mechanism in vivo and in vitro. In vivo, mice were administrated with 6 mg dehydroepiandrosterone (DHEA) per 100 g body weight and fed with 60% high fat diet to induce PCOS. The expression of phosphodiesterases 4 (PDE4) was assessed with RT‐qPCR. The ovary pathology was observed by hematoxylin and eosin staining and follicles were counted. Enzyme‐linked immunosorbent assay was adopted for the estimation of progesterone, testosterone and inflammatory factors and lipid accumulation was observed by Oil Red O staining. With the application of reverse transcription‐quantitative PCR (RT‐qPCR) and western blot, the messenger RNA (mRNA) and protein expressions of low‐density lipoprotein receptor (LDLR) was resolved. In vitro, Cell counting kit‐8 and flow cytometry analysis were applied for the assessment of cell proliferation and apoptosis. The proliferation‐ and apoptosis‐related proteins were appraised with western blot. Additionally, the expressions of PDE‐4 at both mRNA and protein levels were tested with RT‐qPCR and western blot. Here, it was discovered that PDE4 was greatly elevated in PCOS mice and DHEA‐induced ovarian granulosa cells (KGN). In PCOS mice, PDE4 was negative correlated with progesterone and had positive correlation with testosterone. Roflumilast could enhanced progesterone expression, increased the number of primary follicles, preantral follicles and antral follicles but reduced testosterone and decreased the number of cystic follicles in PCOS mice. It was also testified that Roflumilast could inhibit the release of inflammatory factors and lipid accumulation in PCOS mice. Besides, the proliferation of DHEA‐induced KGN cells was enhanced while the apoptosis was declined by Roflumilast, accompanied by elevated contents of PCNA, Ki67 and antiapoptotic protein Bcl‐2. Collectively, Roflumilast inhibited inflammation and lipid accumulation in PCOS mice to improve ovarian function and reduce DHEA‐induced granulosa cell apoptosis.
Guidelines for visualization and analysis of DC in tissues using multiparameter fluorescence microscopy imaging methods
Authors: Bayerl Felix , Bejarano David A. , Bertacchi Giulia , Doffin Anne‐Claire , Gobbini Elisa , Hubert Margaux , Li Lijian , Meiser Philippa , Pedde Anna‐Marie , Posch Wilfried , Rupp Luise , Schlitzer Andreas , Schmitz Marc , Schraml Barbara U. , Uderhardt Stefan , Valladeau‐Guilemond Jenny , Wilflingseder Doris , Zaderer Viktoria , Böttcher Jan P.
Published: January 2023

This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state‐of‐the‐art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy, and functional characterization of mouse and human dendritic cells (DC) from lymphoid organs and various non‐lymphoid tissues. Here, we provide detailed procedures for a variety of multiparameter fluorescence microscopy imaging methods to explore the spatial organization of DC in tissues and to dissect how DC migrate, communicate, and mediate their multiple functional roles in immunity in a variety of tissue settings. The protocols presented here entail approaches to study DC dynamics and T cell cross‐talk by intravital microscopy, large‐scale visualization, identification, and quantitative analysis of DC subsets and their functions by multiparameter fluorescence microscopy of fixed tissue sections, and an approach to study DC interactions with tissue cells in a 3D cell culture model. While all protocols were written by experienced scientists who routinely use them in their work, this article was also peer‐reviewed by leading experts and approved by all co‐authors, making it an essential resource for basic and clinical DC immunologists.
Norms and COVID‐19 health behaviours: A longitudinal investigation of group factors
Authors: Zhou Haochen , Cárdenas Diana , Reynolds Katherine J.
Published: January 2023

Most studies on norms and COVID‐19 have ignored the group‐based and dynamic nature of normative influence where self‐relevant and salient groups might emerge and change along with their impact on health behaviours. The current research seeks to explore these issues using a three‐wave longitudinal design with a representative sample of Australians (Nwave 1 = 3024) where two group sources of potential normative influence (neighbourhood and national groups) and two COVID‐19 health behaviours (physical distancing and hand hygiene) were investigated in May, June/July and September/October 2020. Results indicated that especially from Wave 1 to Wave 2 neighbourhood descriptive norms (rather than national or injunctive norms) had the most impact on health behaviours while controlling for demographic and individual‐level health variables. This demonstrates that groups and associated norms that influence behaviours vary across time. It is concluded that research on norms needs to study which groups matter and when.
Susceptibility of Salmonella serotypes isolated from meat and meat contact surfaces to thermal, acidic, and alkaline treatments and disinfectants
Authors: Manafi Leila , Aliakbarlu Javad , Dastmalchi Saei Habib
Published: January 2023

The present study was conducted to evaluate the response of 29 Salmonella isolates to exposure to thermal (60°C for 2 min), acidic (pH 2.9 for 30 min), and alkaline (pH 11 for 60 min) treatments and investigate the susceptibility of the isolates and their biofilms to disinfectants. The reductions of Salmonella isolates populations subjected to each treatment were analyzed according to their isolation source, serotype, antibiotic resistance pattern, and biofilm formation ability. Median reductions for all of Salmonella isolates populations after thermal, acidic, and alkaline treatments were 1.8, 2.1, and 0.7 log CFU/ml, respectively. The isolates behavior under stress conditions were not related to their isolation source, serotype, or biofilm formation ability. The median reduction after alkaline treatment in non‐MDR (multidrug‐ resistant) isolates populations was significantly (p < .05) higher than MDR isolates. The median reduction in biofilms of moderate biofilm producers by disinfectants was significantly (p < .05) higher than that of strong biofilm producers. In conclusion, Salmonella isolates showed the highest susceptibility to acidic treatment and MDR isolates were more resistant to alkaline treatment than non‐MDR ones. The current study also revealed that the strong biofilm producer isolates were more resistant to disinfectants than moderate biofilm producers. This study facilitated the understanding of the relationship between Salmonella characteristics (isolation source, serotype, antibiotic resistance pattern, and biofilm formation ability) and its susceptibility to thermal, acidic, and alkaline treatments and disinfectants. The findings are helpful for the prevention and control of Salmonella.
Yes‐associated protein regulates glutamate homeostasis through promoting the expression of excitatory amino acid transporter‐2 in astrocytes via β‐catenin signaling
Authors: Xu Xingxing , Wang Jiaojiao , Du Siyu , Shen Xiya , Lian Jiashu , Zhou Jian , Wang Mianxian , Feng Wenjin , Lv Zhaoting , Zhu Junzhe , Jin Lingting , Sun Huankun , Wu Lihao , Wang Xiaoning , Qiu Haoyu , Wang Wei , Teng Honglin , Wang Ying , Huang Zhihui
Published: January 2023

The homeostasis of glutamate is mainly regulated by the excitatory amino acid transporters (EAATs), especially by EAAT2 in astrocytes. Excessive glutamate in the synaptic cleft caused by dysfunction or dysregulation of EAAT2 can lead to excitotoxicity, neuronal death and cognitive dysfunction. However, it remains unclear about the detailed regulation mechanism of expression and function of astrocytic EAAT2. In this study, first, we found increased neuronal death and impairment of cognitive function in YAPGFAP‐CKO mice (conditionally knock out Yes‐associated protein [YAP] in astrocytes), and identified EAAT2 as a downstream target of YAP through RNA sequencing. Second, the expression of EAAT2 was decreased in cultured YAP−/− astrocytes and the hippocampus of YAPGFAP‐CKO mice, and glutamate uptake was reduced in YAP−/− astrocytes, but increased in YAP‐upregulated astrocytes. Third, further investigation of the mechanism showed that the mRNA and protein levels of β‐catenin were decreased in YAP−/− astrocytes and increased in YAP‐upregulated astrocytes. Wnt3a activated YAP signaling and up‐regulated EAAT2 through β‐catenin. Furthermore, over‐expression or activation of β‐catenin partially restored the downregulation of EAAT2, the impairment of glutamate uptake, neuronal death and cognitive decline that caused by YAP deletion. Finally, activation of EAAT2 also rescued neuronal death and cognitive decline in YAPGFAP‐CKO mice. Taken together, our study identifies an unrecognized role of YAP signaling in the regulation of glutamate homeostasis through the β‐catenin/EAAT2 pathway in astrocytes, which may provide novel insights into the pathogenesis of brain diseases that closely related to the dysfunction or dysregulation of EAAT2, and promote the development of clinical strategy.
An event‐based magnetoencephalography study of simulated driving: Establishing a novel paradigm to probe the dynamic interplay of executive and motor function
Authors: Walshe Elizabeth A. , Roberts Timothy P. L. , Ward McIntosh Chelsea , Winston Flaura K. , Romer Dan , Gaetz William
Published: January 2023

Magnetoencephalography (MEG) is particularly well‐suited to the study of human motor cortex oscillatory rhythms and motor control. However, the motor tasks studied to date are largely overly simplistic. This study describes a new approach: a novel event‐based simulated drive made operational via MEG compatible driving simulator hardware, paired with differential beamformer methods to characterize the neural correlates of realistic, complex motor activity. We scanned 23 healthy individuals aged 16–23 years (mean age = 19.5, SD = 2.5; 18 males and 5 females, all right‐handed) who completed a custom‐built repeated trials driving scenario. MEG data were recorded with a 275‐channel CTF, and a volumetric magnetic resonance imaging scan was used for MEG source localization. To validate this paradigm, we hypothesized that pedal‐use would elicit expected modulation of primary motor responses beta‐event‐related desynchronization (B‐ERD) and movement‐related gamma synchrony (MRGS). To confirm the added utility of this paradigm, we hypothesized that the driving task could also probe frontal cognitive control responses (specifically, frontal midline theta [FMT]). Three of 23 participants were removed due to excess head motion (>1.5 cm/trial), confirming feasibility. Nonparametric group analysis revealed significant regions of pedal‐use related B‐ERD activity (at left precentral foot area, as well as bilateral superior parietal lobe: p < .01 corrected), MRGS (at medial precentral gyrus: p < .01 corrected), and FMT band activity sustained around planned braking (at bilateral superior frontal gyrus: p < .01 corrected). This paradigm overcomes the limits of previous efforts by allowing for characterization of the neural correlates of realistic, complex motor activity in terms of brain regions, frequency bands and their dynamic temporal interplay.
Time trends in treatment patterns and survival of older patients with synchronous metastatic colorectal cancer in the Netherlands: A population‐based study
Authors: Baltussen Joosje C. , de Glas Nienke A. , Liefers Gerrit‐Jan , Slingerland Marije , Speetjens Frank M. , van den Bos Frederiek , Cloos‐van Balen Marissa , Verschoor Arjan J. , Jochems Anouk , Spierings Leontine E. A. M. M. , Holterhues Cynthia , van Gerven Leander A. , Mooijaart Simon P. , Portielje Johanneke E. A. , Derks Marloes G. M.
Published: January 2023

New treatment strategies have improved survival of metastatic colorectal cancer in trials. However, it is not clear whether older patients benefit from these novel therapies, as they are often not included in pivotal trials. Therefore, we investigated treatment patterns and overall survival over time in older patients with metastatic colorectal cancer in a population‐based study. We identified 22.192 Dutch patients aged ≥70 years diagnosed with synchronous metastatic colorectal cancer between 2005 and 2020 from the Netherlands Cancer Registry. Changes in treatment over time were assessed with logistic regression models. Survival was assessed by Cox proportional hazard ratios (HR). Results showed that chemotherapy use increased between 2005 and 2015, but declined from 2015 onwards, while more patients received best supportive care. Over time, fewer patients underwent primary tumor resection alone. Although survival of both metastatic colon and rectal cancer improved until 2014, survival of colon cancer decreased from 2014 onwards (HR 1.04, 95% confidence interval [CI] 1.01‐1.05), which was seen in all age groups. Survival of metastatic rectal cancer patients remained unchanged from 2014 onwards (HR 1.00, 95% CI 0.98‐1.03) in all age groups. In conclusion, treatment patterns of Dutch older patients with synchronous metastatic colorectal cancer rapidly changed from 2005 to 2020, with increasing percentages of patients receiving best supportive care. Survival of metastatic colon cancer decreased from 2014 onwards. The implementation of a colorectal cancer screening program and patient selection might explain why only a subset of older patients seem to benefit from the availability of novel treatment options.
A Phase IIb, single arm, multicenter trial of sacituzumab govitecan in Chinese patients with metastatic triple‐negative breast cancer who received at least two prior treatments
Authors: Xu Binghe , Ma Fei , Wang Tao , Wang Shusen , Tong Zhongsheng , Li Wei , Wu Xinhong , Wang Xiaojia , Sun Tao , Pan Yueyin , Yao Herui , Wang Xian , Luo Ting , Yang Jin , Zeng Xiaohua , Zhao Weihong , Cong Xiuyu Julie , Chen Jiongjie
Published: January 2023

Refractory or relapsing metastatic triple‐negative breast cancer (mTNBC) has a poor prognosis. Sacituzumab govitecan (SG) is a novel antibody‐drug conjugate, targeting human trophoblast cell‐surface antigen 2 (Trop‐2). This is the first report of SG's efficacy and safety in Chinese patients with mTNBC. EVER‐132‐001 (NCT04454437) was a multicenter, single‐arm, Phase IIb study in Chinese patients with mTNBC who failed ≥2 prior chemotherapy regimens. Eligible patients received 10 mg/kg SG on Days 1 and 8 of each 21‐day treatment cycle, until disease progression/unacceptable toxicity. The primary endpoint was objective response rate (ORR) assessed by the Independent Review Committee. Secondary endpoints included: duration of response (DOR), clinical benefit rate (CBR), progression‐free survival (PFS), overall survival (OS) and safety. Eighty female Chinese patients (median age 47.6 years; range 24‐69.9 years) received ≥1 SG dose with a median of 8 treatment cycles by the cutoff date (August 6, 2021). Median number of prior systemic cancer treatments was 4.0 (range 2.0‐8.0). ORR and CBR were reported 38.8% (95% confidence interval [CI]: 28.06‐50.30) and 43.8% (95% CI, 32.68‐55.30) of patients, respectively. The median PFS was 5.55 months (95% CI, 4.14‐N/A). SG‐related Grade ≥3 treatment‐emergent adverse events (TEAEs) were reported in 71.3%, the most common were neutrophil count decreased (62.5%), white blood cell count decreased (48.8%) and anemia (21.3%); 6.3% discontinued SG because of TEAEs. SG demonstrated substantial clinical activity in heavily pretreated Chinese patients with mTNBC. The observed safety profile was generally manageable.
Transcriptomic analyses reveal three distinct molecular subgroups of Merkel cell carcinoma with differing prognoses
Authors: Sundqvist Benjamin Z. , Kilpinen Sami K. , Böhling Tom O. , Koljonen Virve S. K. , Sihto Harri J.
Published: January 2023

Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy with a poor prognosis and an unknown cell of origin. Proffered cells of origin include epithelial stem cells of the hair follicle or interfollicular epidermis, dermal stem cells and pro/pre‐ or pre‐B cells. MCC has also been proposed to have more than one cell of origin and indeed to represent more than one type of carcinoma, currently grouped together due to phenotypic similarities. We explored the heterogeneous nature of MCC by studying the most variably expressed genes with the goal of identifying gene expression patterns that are either clinically relevant or have implications regarding the cell(s) of origin. We performed RNA sequencing on primary tumor samples from 102 patients and identified the top 200 most variably expressed genes. These genes and the tumor samples were hierarchically clustered based on their expression. The functions of three gene clusters exhibiting clearly divergent expression between samples were studied by cross‐referencing the lists of genes with online databases. High expression of a gene cluster related to embryonic developmental processes and low expression of a gene cluster related to neuroendocrine processes distinguished Merkel cell polyomavirus (MCPyV)‐negative tumors from MCPyV‐positive tumors. Furthermore, two prognostically relevant subgroups of MCPyV‐positive MCC were identified based on dichotomic expression of genes related to epidermal structures and processes. We identified three distinct molecular subgroups of MCC with prognostic relevance. We propose that the dichotomic expression of epidermis‐related genes might reflect both an epidermal and a nonepidermal origin for MCPyV‐positive MCC.
COVID‐19 vaccination in pregnancy: Need for global pharmaco‐vigilance
Authors: Sarwal Yamini , Sarwal Rakesh
Published: January 2023

Coronavirus infectious disease has been around for more than 2 years as a pandemic, but now appears to have taken the form of an endemic. COVID‐19 vaccination in pregnant women is presently being recommended and followed in most countries. However, robust scientific evidence on safety of the vaccine in the medium or long term, or regarding any adverse effects, is lacking. We searched the PubMed and gray literature for evidence on medium‐ or long‐term effects of COVID‐19 vaccination during pregnancy on the mother or her fetus/newborn and found limited data on this subject. Moreover, available evidence comes almost exclusively from the Western world. Any adverse effects of COVID‐19 vaccination during or after pregnancy may take time to manifest. Therefore, there is a need to keep the cohort of vaccinated women and their children under scrutiny for any possible adverse effects. This is also needed to build confidence in the long term in the vaccines. A global pharmaco‐vigilance or post‐marketing surveillance network covering pregnant recipients of COVID‐19 vaccines can identify and help to address any medium‐ or long‐term adverse effects of the COVID‐19 vaccines on pregnancy and the newborn.
Strategies and tools in illumina and nanopore‐integrated metagenomic analysis of microbiome data
Authors: Xia Yu , Li Xiang , Wu Ziqi , Nie Cailong , Cheng Zhanwen , Sun Yuhong , Liu Lei , Zhang Tong
Published: January 2023

Metagenomic strategy serves as the foundation for the ecological exploration of novel bioresources (e.g., industrial enzymes and bioactive molecules) and biohazards (e.g., pathogens and antibiotic resistance genes) in natural and engineered microbial systems across multiple disciplines. Recent advancements in sequencing technology have fostered rapid development in the field of microbiome research where an increasing number of studies have applied both illumina short reads (SRs) and nanopore long reads (LRs) sequencing in their metagenomic workflow. However, given the high complexity of an environmental microbiome data set and the bioinformatic challenges caused by the unique features of these sequencing technologies, integrating SRs and LRs is not as straightforward as one might assume. The fast renewal of existing tools and growing diversity of new algorithms make access to this field even more difficult. Therefore, here we systematically summarized the complete workflow from DNA extraction to data processing strategies for applying illumina and nanopore‐integrated metagenomics in the investigation in environmental microbiomes. Overall, this review aims to provide a timely knowledge framework for researchers that are interested in or are struggling with the SRs and LRs integration in their metagenomic analysis. The discussions presented will facilitate improved ecological understanding of community functionalities and assembly of natural, engineered, and human microbiomes, benefiting researchers from multiple disciplines.
Destabilized microbial networks with distinct performances of abundant and rare biospheres in maintaining networks under increasing salinity stress
Authors: Li Changchao , Jin Ling , Zhang Chao , Li Shuzhen , Zhou Tong , Hua Zhongyi , Wang Lifei , Ji Shuping , Wang Yanfei , Gan Yandong , Liu Jian
Published: January 2023

Global changes such as seawater intrusion and freshwater resource salinization increase environmental stress imposed on the aquatic microbiome. A strong predictive understanding of the responses of the aquatic microbiome to environmental stress will help in coping with the “gray rhino” events in the environment, thereby contributing to an ecologically sustainable future. Considering that microbial ecological networks are tied to the stability of ecosystem functioning and that abundant and rare biospheres with different biogeographic patterns are important drivers of ecosystem functioning, the roles of abundant and rare biospheres in maintaining ecological networks need to be clarified. Here we showed that, with the increasing salinity stress induced by the freshwater‐to‐seawater transition, the microbial diversity reduced significantly and the taxonomic structure experienced a strong succession. The complexity and stability of microbial ecological networks were diminished by the increasing stress. The composition of the microorganisms supporting the networks underwent sharp turnovers during the freshwater‐to‐seawater transition, with the abundant biosphere behaving more robustly than the rare biosphere. Notably, the abundant biosphere played a much more important role than the rare biosphere in stabilizing ecological networks under low‐stress environments, but the difference between their relative importance narrowed significantly with the increasing stress, suggesting that the environmental stress weakened the “Matthew effect” in the microbial world. With in‐depth insights into the aquatic microbial ecology under stress, our findings highlight the importance of adjusting conservation strategies for the abundant and rare biospheres to maintain ecosystem functions and services in response to rising environmental stress.
Prevalence of veterinary antibiotics in natural and organic fertilizers from animal food production and assessment of their potential ecological risk
Authors: Patyra Ewelina , Nebot Carolina , Gavilán Rosa Elvira , Kwiatek Krzysztof , Cepeda Alberto
Published: January 2023

BACKGROUND

Veterinary antibiotics are emerging contaminants and enter into soil principally by agricultural application of organic fertilizers. This article presents the results of the research obtained for the analyzed 70 samples of fertilizers (pig and poultry manure and slurry and digestate) for various classes of antibiotics.

RESULTS

Doxycycline, oxytetracycline, tetracycline, lincomycin, tiamulin and enrofloxacin were found in tested samples. Doxycycline was found as a dominant compound, and its highest concentration was 175 mg/kg in pig manure. This investigation indicated that fertilization with manure, especially animal feces, might be the primary source of antibiotics. Additionally, a risk assessment based on a risk quotient was carried out, which showed that the determined concentrations of antibiotics in fertilizers may pose a threat to soil microorganisms.

CONCLUSIONS

Results suggested that the ecological risk effects of antibiotic contamination on soil bases and their potential adverse risk on human health needs special attention. © 2023 Society of Chemical Industry.
Environmental and ecological drivers of harmful algal blooms revealed by automated underwater microscopy
Authors: Kenitz Kasia M. , Anderson Clarissa R. , Carter Melissa L. , Eggleston Emily , Seech Kristi , Shipe Rebecca , Smith Jayme , Orenstein Eric C. , Franks Peter J. S. , Jaffe Jules S. , Barton Andrew D.
Published: January 2023

In recent years, harmful algal blooms (HABs) have increased in their severity and extent in many parts of the world and pose serious threats to local aquaculture, fisheries, and public health. In many cases, the mechanisms triggering and regulating HAB events remain poorly understood. Using underwater microscopy and Residual Neural Network (ResNet‐18) to taxonomically classify imaged organisms, we developed a daily abundance record of four potentially harmful algae (Akashiwo sanguinea, Chattonella spp., Dinophysis spp., and Lingulodinium polyedra) and major grazer groups (ciliates, copepod nauplii, and copepods) from August 2017 to November 2020 at Scripps Institution of Oceanography pier, a coastal location in the Southern California Bight. Random Forest algorithms were used to identify the optimal combination of environmental and ecological variables that produced the most accurate abundance predictions for each taxon. We developed models with high prediction accuracy for A. sanguinea (), Chattonella spp. (), and L. polyedra (), whereas models for Dinophysis spp. showed lower prediction accuracy (). Offshore nutricline depth and indices describing climate variability, including El Niño Southern Oscillation, Pacific Decadal Oscillation, and North Pacific Gyre Oscillation, that influence regional‐scale ocean circulation patterns and environmental conditions, were key predictor variables for these HAB taxa. These metrics of regional‐scale processes were generally better predictors of HAB taxa abundances at this coastal location than the in situ environmental measurements. Ciliate abundance was an important predictor of Chattonella and Dinophysis spp., but not of A. sanguinea and L. polyedra. Our findings indicate that combining regional and local environmental factors with microzooplankton populations dynamics can improve real‐time HAB abundance forecasts.