bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute respiratory distress syndrome after spontaneous rupture of a large pulmonary hydatid cyst in a 17‐year‐old male: A case report
Authors: Salimi Mehdi , Assar Shirin , Mohamadzadeh Dena , Kanjorpor Asal
Published: April 2023

Pulmonary hydatid cysts (PHC) and their complications are still a health concern in endemic countries. Here we described a 17‐year‐old male presented with a large PHC with a spontaneous rupture. He developed acute respiratory distress syndrome (ARDS) requiring mechanical ventilation. He was treated with albendazole, broad‐spectrum antibiotics, and corticosteroids. The patient's general condition did not allow any attempt for surgical resection of the cyst. He was discharged in stable condition after one month and referred to a thoracic surgeon for resection of the cyst. As far as we know ARDS after hydatid cyst rupture was rarely reported, and through this case report we aimed to raise awareness of this possible life‐threatening complication.
Single‐Atom Fe Catalyst for Catalytic Ethane Dehydrogenation to Ethylene
Authors: Yu Xiaogang , Li Guomin , Tao Shenghui , Wang Bin , Liu Ce , Jing Huanwang , Shi Feng , Cui Xinjiang
Published: April 2023

The single atom catalysts (SACs) show unique catalytic performance in heterogeneous reactions owing to unsaturated coordination sites and high metal atom dispersion. Herein, a simple wet impregnation method was utilized to synthetize of Fe−Al2O3 catalysts. The Fourier transformation infrared spectroscopy (FTIR) revealed that abundant OH group attached to the support (Al2O3) surface facilitating formation of isolated Fe single atom. High resolution transmission electron microscope (HR‐TEM) and extended X‐ray absorption fine structure (EXAFS) confirmed the Fe single atom architecture. Fe−Al2O3 (4.5 wt %) performed enhanced stability and activity on ethane dehydrogenation reaction.
Chemo‐Enzymatic One‐Pot Oxidation of Cyclohexane via in‐situ H2O2 Production over Supported AuPdPt Catalysts
Authors: Stenner Alex , Lewis Richard J. , Brehm Joseph , Qin Tian , López‐Martín Ángeles , Morgan David J. , Davies Thomas E. , Chen Liwei , Liu Xi , Hutchings Graham J.
Published: April 2023

The introduction of dopant concentrations of Pt into supported AuPd nanoparticles, when used in conjunction with an evolved unspecific peroxygenase (UPO) from Agrocybe aegerita (PaDa‐I) is demonstrated to offer high efficacy towards the one‐pot selective oxidation of cyclohexane to KA oil (cyclohexanol and cyclohexanone), via the in‐situ synthesis of H2O2. The optimised AuPdPt/TiO2/PaDa‐I system achieves significant improvements over analogous AuPd or Pd‐only formulations or the use of commercially available H2O2, with this attributed to the increased rate of H2O2 production by the chemo‐catalyst, which results from the electronic modification of Pd species via Pt incorporation, upon the formation of trimetallic nanoalloys.
From AuPd Nanoparticle Alloys towards Core‐Shell Motifs with Enhanced Alcohol Oxidation Activity
Authors: Silva Tiago A. G. , Teixeira‐Neto Érico , Borges Laís R. , Neves‐Garcia Tomaz , Braga Adriano H. , Rossi Liane M.
Published: April 2023

The best activity of bimetallic AuPd nanoparticles for alcohol oxidation reaction is usually achieved by adjusting the Au/Pd molar ratio. Herein, alloy AuPd nanoparticles of ∼2.5–3.5 nm, ranging from Au‐rich to Pd‐rich compositions, were synthesized through a sol‐immobilization method. A calcination step under air conditions caused an increase in size up to 5.5 nm, but also driven the segregation of Pd to the surface, which generated an Au rich core with Pd on the shell. At high Pd content, the shell structure is formed by PdO. The catalytic activity of Pd‐rich samples (1 : 1, 1 : 2 and 1 : 4 Au : Pd) for benzyl alcohol oxidation increased ∼4‐fold after calcination. Upon reduction with H2, surface PdO motifs are reduced to Pd that did not dissolve back into the AuPd alloy core, maintaining the metallic Pd shell. The catalytic activity decreased. Therefore, restructuring alloyed AuPd nanoparticles into core‐shell like structures with PdO in the shell is beneficial to the catalytic activity, but reduction of PdO layer was detrimental. These results provide new insights on the optimization of AuPd catalysts, considering not only the Au/Pd molar ratio, but also the importance of PdO, which was not anticipated in the previous literature.
Real‐Time Observation for Dynamic Oscillation during Self‐Assembly and Clearance of Aβ42
Authors: Yao Chun‐Nien , Wu Te‐Haw , Cheng Pin‐Yen , Tsao Yueh‐Chia , Lu Yen‐Fei , Chu Li‐Kang , Chiu Chi‐Cheng , Lin Shu‐Yi
Published: April 2023

The dynamic oscillation implicated in structural heterogeneity during the self‐assembly of amyloid peptide 1–42 (Aβ42) may play a crucial role in eliciting cellular responses. We developed a real‐time monitoring platform to observe an oscillatory non‐equilibrium interaction that dominated the Aβ42 clearance by neuronal cells during interplay with an oscillator (lipopolysaccharide, LPS). Molecular dynamics studies indicated that the electrostatic and hydrophobic segments of LPS involved in the temporary heteromolecular association and slightly decelerated the intrinsic thermally–induced protein dynamics of Aβ42. A bait‐specific intervention strategy could temporarily slow down the self‐propagation of Aβ42 to extend the lifetime of autonomous oscillation and augment Aβ42 clearance of neuronal cells. The lifetime increment of oscillation shows a bait concentration‐dependent manner to reflect the non‐equilibrium binding strength. This relationship may serve as a predictor for Alzheimer's disease drug discovery.
Ratiometric Fluorescence Assay for Pyrophosphate Based on Sulfur Nanodots Decorated Metal‐Organic Frameworks
Authors: Ma Jinzhu , Wang Shuai , Wang Tianle , Ma Jing , Wang Zhenguang
Published: April 2023

Selective and sensitive detection of inorganic pyrophosphate (PPi) are of great significance both for clinical applications and fundamental research. In this work, a ratiometric fluorescent probe was developed by decorating a porphyrin‐based metal‐organic framework (PCN‐224) with sulfur nanodots (S‐dots). The red‐fluorescence of PCN‐224 was significantly promoted (more than 6‐fold) by S‐dots through inhibiting molecular motion of porphyrin ligand, which also provided active sites for the detection of Cu2+ and PPi. Cu2+ could selectively quench the red‐fluorescence of PCN‐224 through coordination with porphyrin ligand, and the competition reaction between PPi and Cu2+ resulted in the decomposing of coordination and recovery of red‐fluorescence. The blue‐fluorescence from S‐dots was deemed as effective reference, which provided a built‐in correction in complex environments. Based on these photophysical properties, a ratiometric fluorescence assay was developed for the quantitative detection of Cu2+ and PPi, with a limit of detection of 0.11 and 2.66 μM, respectively. The accuracy and practical applications of assays were also demonstrated by detection in tap water and human serum samples.
Intermolecular Triazene Alkene Cycloaddition via Lewis Base Catalysis: Access to Diverse Trifluoromethylated Pyrazolines
Authors: Peng Shiyong , Zhu Huijuan , Wu Haiyun , Hao Di , Yang Liangliang , Liu Yangyang , Gong Xiaojie , Wei Jianhe , Wang Lei
Published: April 2023

A novel approach to chemoselective synthesis of biologically important CF3‐subsituted pyrazolines was developed via a Lewis base catalyzed intermolecular triazene cycloaddition reaction of an array of terminal/internal alkenes with CF3CHN2. This strategy features a catalytic amount of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene, high yields (up to 95 %), wide substrate scope and excellent functional group tolerance (54 examples). Importantly, we preformed scaffold diversification of a panel of known pharmaceuticals, natural products, and bioactive heterocycles to generate the corresponding pyrazoline derivatives with potential broad bioactivities for further development.
Stereochemistry‐activity relationship of ceramide‐induced exosome production to clear amyloid‐β in Alzheimer's disease
Authors: Abdelrasoul Mariam , Yuyama Kohei , Swamy Mahadeva M. M. , Murai Yuta , Monde Kenji
Published: April 2023

Stereochemistry has a substantial impact on the biological activity of various drugs. We investigated the role of stereochemistry of ceramides in inducing the production of exosomes, a type of extracellular vesicle, from neuronal cells, with a potential benefit in improving the clearance of amyloid‐β (Aβ), a causal agent of Alzheimer's disease. A stereochemical library of diverse ceramides with different tail lengths was synthesized with the purpose of varying stereochemistry (D‐erythro: DE, D‐threo: DT, L‐erythro: LE, L‐threo: LT) and hydrophobic tail length (C6, C16, C18, C24). The exosome levels were quantified using TIM4‐based exosome enzyme‐linked immunosorbent assay after concentrating the conditioned medium using centrifugal filter devices. The results revealed a pivotal role of stereochemistry in determining the biological activity of ceramide stereoisomers, with the superiority of those based on DE and DT stereochemistry with C16 and C18 tails, which demonstrated significantly higher exosome production, without a significant change in the particle size of the released exosomes. In transwell experiments with Aβ‐expressed neuronal and microglial cells, DE‐ and DT‐ceramides with C16 and C18 tails significantly decreased extracellular Aβ levels. The results reported here are promising in the design of non‐classic therapies for the treatment of Alzheimer's disease.
C‐GlycosideSynthesis Enabled by Nickel Catalysis
Authors: Shang Weidong , Shi Rong , Niu Dawen
Published: April 2023

Comprehensive Summary

C‐Glycosides are critical, naturally occurring products and medicinal candidates, and extensive efforts have been made to explore efficient approaches for creating C‐glycosidic bonds. Transition‐metal‐catalysis, particularly nickel‐catalyzed C‐glycosylation reactions constitute a promising strategy. However, achieving a stereoselective synthesis of α‐ and β‐C‐glycosides has been a long‐standing challenge. To address this problem, a variety of nickel‐mediated strategies have been developed. This review highlights recent developments in the nickel‐catalyzed diastereoselective C‐glycosylation reactions and briefly summarizes the mechanistic understandings of these methods.
Explainability and causability in digital pathology
Authors: Plass Markus , Kargl Michaela , Kiehl Tim‐Rasmus , Regitnig Peter , Geißler Christian , Evans Theodore , Zerbe Norman , Carvalho Rita , Holzinger Andreas , Müller Heimo
Published: April 2023

The current move towards digital pathology enables pathologists to use artificial intelligence (AI)‐based computer programmes for the advanced analysis of whole slide images. However, currently, the best‐performing AI algorithms for image analysis are deemed black boxes since it remains – even to their developers – often unclear why the algorithm delivered a particular result. Especially in medicine, a better understanding of algorithmic decisions is essential to avoid mistakes and adverse effects on patients. This review article aims to provide medical experts with insights on the issue of explainability in digital pathology. A short introduction to the relevant underlying core concepts of machine learning shall nurture the reader's understanding of why explainability is a specific issue in this field. Addressing this issue of explainability, the rapidly evolving research field of explainable AI (XAI) has developed many techniques and methods to make black‐box machine‐learning systems more transparent. These XAI methods are a first step towards making black‐box AI systems understandable by humans. However, we argue that an explanation interface must complement these explainable models to make their results useful to human stakeholders and achieve a high level of causability, i.e. a high level of causal understanding by the user. This is especially relevant in the medical field since explainability and causability play a crucial role also for compliance with regulatory requirements. We conclude by promoting the need for novel user interfaces for AI applications in pathology, which enable contextual understanding and allow the medical expert to ask interactive ‘what‐if’‐questions. In pathology, such user interfaces will not only be important to achieve a high level of causability. They will also be crucial for keeping the human‐in‐the‐loop and bringing medical experts' experience and conceptual knowledge to AI processes.
Anomaly detection for high‐dimensional dynamic data stream using stacked habituation autoencoder and union kernel density estimator
Authors: Zeng Zhixia , Huang Ruohe , Xiao Ruliang , Lin Xinhong , Zhang Shi
Published: April 2023

With the rapid development of communication technology, various complex heterogeneous sensor network applications produce a large number of high‐dimensional dynamic data streams, which results in more difficult to anomaly detection than ever before. So, anomaly detection for high‐dimensional dynamic data streams is of a more and more challenging problem. This paper proposes a novel method for detecting anomalies in high‐dimensional dynamic data streams by utilizing several components. Firstly, it uses a stacked habituation autoencoder with habituation physiological mechanism to detect similarity anomalies more easily and capture feature relationships. Secondly, a union kernel density estimator with micro‐cluster is designed to improve online anomaly detection accuracy by estimating the data density. Lastly, candidate anomaly sets and a delayed processing approach are utilized to cope with conceptual drift and evolution in the data stream, allowing the system to adapt to changes in the data over time. Extensive experiments on four high‐dimensional dynamic data streams of the Internet of Things show that the proposed method is very effective.
Conceptualizing the digital therapeutic alliance in the context of fully automated mental health apps: A thematic analysis
Authors: Tong Fangziyun , Lederman Reeva , D'Alfonso Simon , Berry Katherine , Bucci Sandra
Published: April 2023

Fully automated mental health apps provide a promising opportunity for increasing access to mental health care and resources. Given this opportunity, continued research into the utility and effectiveness of mental health apps is crucial. Therapeutic alliance (TA) refers to the relationship between a client and a healthcare professional, and has been shown to be an important predictor of clinical outcomes in face‐to‐face therapy. Given the significance of TA in traditional therapy, it is important to explore whether the notion of a digital therapeutic alliance (DTA) in the context of fully automated mental health apps also plays an important role in clinical outcomes. Current evidence shows that the conceptualization of DTA in the context of fully automated mental health apps can be potentially different to TA in face‐to‐face therapy. Thus, a new DTA conceptual model is necessary for comprehensively understanding the mechanisms underpinning DTA for fully automated mental health apps. To the best of our knowledge, this is the first study that qualitatively explored the dimensions of a DTA in the context of fully automated mental health apps. We conducted interviews with 20 users of mental health apps to explore the key dimensions comprising DTA in the context of fully automated mental health apps. We found that although conceptualizations of DTA and TA have shared dimensions, flexibility and emotional experiences are unique domains in DTA. On the other hand, although agreement on goals between a therapist and a client is important in face to face therapy, we found that users can have an alliance with an app without a goal. The importance of goal needs further investigations.
Tilianin alleviates lipid deposition and fibrosis in mice with nonalcoholic steatohepatitis by activating the PPARα/Nnat axis
Authors: Ke Fan , Wu Xu , Zheng Jing , Li Cuihong
Published: April 2023

The understanding and treatment of nonalcoholic steatohepatitis (NASH) are still very limited. This study reports the therapeutic effect of tilianin on mice with NASH and further explores its possible molecular mechanisms. A mice model of NASH was established using low‐dose streptozotocin combined with a high‐fat diet and tilianin treatment. Liver function was assessed by determining serum aspartate aminotransferase and alanine aminotransferase in serum. Interleukin (IL)‐1β, IL‐6, transforming growth factor β1 (TGF‐β1), and tumor necrosis factor α (TNF‐α) levels in serum were determined. Hepatocyte apoptosis was assessed using terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate‐biotin nick end labeling staining. Oil Red O staining and boron dipyrrin staining were used to determine lipid deposition in liver tissues. Masson staining was used to evaluate liver fibrosis, and immunohistochemistry and western blot analysis were used to determine the expression of target proteins. Tilianin treatment significantly ameliorated liver function, inhibited hepatocyte apoptosis, and reduced lipid deposition and liver fibrosis in mice with NASH. The expression of neuronatin (Nnat) and peroxisome proliferator‐activated receptor (PPAR) α was upregulated, whereas that of sterol regulatory element‐binding protein 1 (SREBP‐1), TGF‐β1, nuclear factor (NF)‐κB p65, and phosphorylated p65 was downregulated in the liver tissues of mice with NASH after tilianin treatment. The above effects of tilianin were significantly reversed after Nnat knock‐down, but its effect on PPARα expression was unaffected. Thus, the natural drug tilianin shows potential in treatig NASH. Its mechanism of action may be related to the targeted activation of PPARα/Nnat, thereby inhibiting the activation of the NF‐κB signaling pathway.
Development of transdiagnostic clinical risk prediction models for 12‐month onset and course of eating disorders among adolescents in the community
Authors: Mitchison Deborah , Wang Shirley B. , Wade Tracey , Haynos Ann F. , Bussey Kay , Trompeter Nora , Lonergan Alexandra , Tame Jack , Hay Phillipa
Published: April 2023

Objective

To develop and internally validate risk prediction models for adolescent onset and persistence of eating disorders.

Methods

N = 963 Australian adolescents (11–19 years) in the EveryBODY Study cohort completed online surveys in 2018 and 2019. Models were built to predict 12‐month risk of (1) onset, and (2) persistence of a DSM‐5 eating disorder.

Results

Onset Model. Of the n = 687 adolescents without an eating disorder at baseline, 16.9% were identified with an eating disorder after 12 months. The prediction model was based on evidence‐based risk factors for eating disorder onset available within the dataset (sex, body mass index percentile, strict weight loss dieting, history of bullying, psychological distress, weight/shape concerns). This model showed fair discriminative performance (mean AUC = .75). The most important factors were psychological distress, weight and shape concerns, and female sex. Diagnostic Persistence Model. Of the n = 276 adolescents with an eating disorder at baseline, 74.6% were identified as continuing to meet criteria for an eating disorder after 12 months. The prediction model for diagnostic persistence was based on available evidence‐based risk factors for eating disorder persistence (purging, distress, social impairment). This model showed poor discriminative performance (mean AUC = .65). The most important factors were psychological distress and self‐induced vomiting for weight control.

Discussion

We found preliminary evidence for the utility of a parsimonious model for 12‐month onset of an eating disorder among adolescents in the community. Future research should include additional evidence‐based risk factors and validate models beyond the original sample.

Public Significance

This study demonstrated the feasibility of developing parsimonious and accurate models for the prediction of future onset of an eating disorder among adolescents. The most important predictors in this model included psychological distress and weight and shape concerns. This study has laid the ground work for future research to build and test more accurate prediction models in diverse samples, prior to translation into a clinical tool for use in real world settings to aid decisions about referral to early intervention.
Perspectives on relapse prevention following intensive treatment of anorexia nervosa: A focus group study
Authors: Pagano Nikki , Glasofer Deborah R. , Attia Evelyn , Ruggiero Julia , Eziri Kelechi , Goldstein Carly M. , Steinglass Joanna E.
Published: April 2023

Objective

Including the perspectives of individuals with lived experience of mental health issues is a critical step in research and treatment development. Focus groups with patients with a history of treatment for anorexia nervosa (AN) were conducted in anticipation of a clinical trial of Relapse Prevention and Changing Habits (REACH+).

Methods

Seven female adults (23–51 years) who had previously received inpatient treatment for AN, now in remission, participated in one of two semistructured focus groups. Rapid qualitative analysis was used to examine participants' contributions and identify common topics.

Results

Transcript analysis yielded three topics related to relapse prevention: (1) recovery aids, including a sense of agency in treatment decisions and finding new interests/passions, (2) recovery hindrances, such as lack of access to care, and (3) identification of members of support system. Aspects of REACH+ received positive feedback, such as continuity of care from the inpatient setting and the use of telehealth. Viewpoints differed with respect to the helpfulness of obtaining patient weights in treatment. The REACH+ online platform received positive comments regarding content and usability, as well as suggestions for additional content.

Discussion

Qualitative feedback from patients with a history of AN highlighted the value of engaging patients in their own treatment decisions, as well as in treatment design and innovation. Within this small group, there were differences of opinion about treatment components, specifically weight assessment, that suggest the need for further data. User‐centered design provides opportunities to improve the acceptability and, therefore, dissemination of novel treatments.

Public Significance

Relapse prevention is a critical treatment need for patients with anorexia nervosa, as this illness too often follows a protracted course. There are challenges in both obtaining specialized care and in retaining patients in treatment. Here, patient perspectives on these challenges offer input to allow for optimization of relapse prevention treatment. Shared decision‐making may be particularly valuable to support an individual's sense of agency and engagement in care.
Pulmonary artery catheter usage in diagnosis of Shoshin beriberi presented with unexplained lactic acidosis
Authors: Hung Yi‐Hsin , Yu An‐Li , Chen Chun‐Kai , Liao Min‐Tsun , Hsieh Mu‐Yang , Chen Wen‐Jone
Published: April 2023

Wet beriberi is a rare but fatal disease in modern society. The nonspecific clinical manifestations, including symptoms of heart failure and recalcitrant lactic acidosis, can prevent timely diagnosis. The use of a pulmonary artery catheter can promptly confirm a high cardiac output state and plays a crucial role in rapidly deteriorating cases. Appropriate treatment with intravenous administration of thiamine leads to dramatic recovery within hours. We present two cases of Shoshin beriberi, a fulminant variant of wet beriberi, diagnosed in 2016 and 2022 at our institute. The patients experienced haemodynamic collapse and refractory lactic acidosis, which were successfully diagnosed with the use of a pulmonary artery catheter and reversed by thiamine supplementation. We also reviewed 19 cases of wet beriberi reported between 2010 and 2022.
Piano‐Stool Ruthenium N‐Heterocyclic Carbene Complexes for gem‐Specific Catalytic Dimerization of Terminal Alkynes
Authors: Hayashi Kasumi , Liang Qiuming , Philippi Franka , Song Datong
Published: April 2023

A series of piano‐stool Ru−NHC (NHC=N‐heterocyclic carbene) complexes have been prepared and characterized. The NHC ligands used herein have varying wingtip groups, showing the impact of steric congestion on the selectivity for the catalytic dimerization of terminal alkynes.
I2‐Mediated Oxidative Amidation of Aryl Methyl Ketones: Synthesis of Primary α‐Ketoamides Using Ammonium Carbamodithioate as Amine Surrogate
Authors: Wang An‐Jing , Zhang Yu‐Die , Nan Wen‐Jing , Liu Shan , Shu Wen‐Ming , Gong Yin‐Xiang
Published: April 2023

Here we report the preparation of primary α‐ketoamides via a highly efficient molecular iodine‐mediated oxidative amidation of aryl methyl ketones with ammonium carbamodithioate. A self‐sequenced iodination/nucleophilic substitution/Kornblum oxidation/amidation mechanism was proposed. In this mechanism, α‐thiocyanatoacetophenone is the key intermediate.
Discovery ofE2730, a novel selective uncompetitiveGAT1inhibitor, as a candidate for anti‐seizure medication
Authors: Fukushima Kazuyuki , Higashiyama Hiroyuki , Kazuta Yuji , Hashimoto Keisuke , Watanabe Naoto , Furuya Yoshiaki , Ito Yoshimasa , Wu Ting , Kosasa Takashi , Talos Delia M. , Song Yeri , Roberts Nicholas S. , Jensen Frances E. , Hanada Takahisa , Ido Katsutoshi
Published: April 2023

Objective

As of 2022, 36 anti‐seizure medications (ASMs) have been licensed for the treatment of epilepsy, however, adverse effects (AEs) are commonly reported. Therefore, ASMs with a wide margin between therapeutic effects and AEs are preferred over ASMs that are associated with a narrow margin between efficacy and risk of AEs. E2730 was discovered using in vivo phenotypic screening and characterized as an uncompetitive, yet selective, inhibitor of γ‐aminobutyric acid (GABA) transporter 1 (GAT1). Here, we describe the preclinical characteristics of E2730.

Methods

Anti‐seizure effects of E2730 were evaluated in several animal models of epilepsy: corneal kindling, 6 Hz–44 mA psychomotor seizure, amygdala kindling, Fragile X syndrome, and Dravet syndrome models. Effects of E2730 on motor coordination were assessed in accelerating rotarod tests. The mechanism of action of E2730 was explored by [3H]E2730 binding assay. The GAT1‐selectivity over other GABA transporters was examined by GABA uptake assay of GAT1, GAT2, GAT3, or betaine/GABA transporter 1 (BGT‐1) stably expressing HEK293 cells. To further investigate the mechanism for E2730‐mediated inhibition of GAT1, in vivo microdialysis and in vitro GABA uptake assays were conducted under conditions of different GABA concentrations.

Results

E2730 showed anti‐seizure effects in the assessed animal models with an approximately >20‐‍fold margin between efficacy and motor incoordination. [3H]E2730 binding on brain synaptosomal membrane was abolished in GAT1‐deficient mice, and E2730 selectively inhibited GAT1‐mediated GABA uptake over other GABA transporters. In addition, results of GABA uptake assays showed that E2730‐mediated inhibition of GAT1 positively correlated to the level of ambient GABA in vitro. E2730 also increased extracellular GABA concentration in hyperactivated conditions but not under basal levels in vivo.

Significance

E2730 is a novel, selective, uncompetitive GAT1 inhibitor, which acts selectively under the condition of increasing synaptic activity, contributing to a wide margin between therapeutic effect and motor incoordination.
Who pays the liquidity cost? Central bank announcements and adverse selection
Authors: Ryu Doojin , Webb Robert I. , Yu Jinyoung
Published: April 2023

This study examines whether the composition of market participants contributes to shaping market liquidity around central bank announcements. By analyzing transaction‐level data from a stock index futures market, we find that the roles of foreign and domestic institutional investors in taking or providing liquidity, respectively, are switched following the news announcements. The participation of domestic (foreign) institutions is negatively (positively) associated with liquidity provision shortly after the announcements, whereas they provide (consume) liquidity in general. The change in domestic institutions' roles is attributed to their advantages in processing local news as it is pronounced when they actively participate. Domestic individuals remain largely noisy and unresponsive. Overall, the results support the existence of adverse selection costs in the order‐driven context and imply that institutional investors may trade with the wind when they have information superiority.
Automatic and manual segmentation of the piriform cortex: Method development and validation in patients with temporal lobe epilepsy and Alzheimer's disease
Authors: Steinbart David , Yaakub Siti N. , Steinbrenner Mirja , Guldin Lynn S. , Holtkamp Martin , Keller Simon S. , Weber Bernd , Rüber Theodor , Heckemann Rolf A. , Ilyas‐Feldmann Maria , Hammers Alexander ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: April 2023

The piriform cortex (PC) is located at the junction of the temporal and frontal lobes. It is involved physiologically in olfaction as well as memory and plays an important role in epilepsy. Its study at scale is held back by the absence of automatic segmentation methods on MRI. We devised a manual segmentation protocol for PC volumes, integrated those manually derived images into the Hammers Atlas Database (n = 30) and used an extensively validated method (multi‐atlas propagation with enhanced registration, MAPER) for automatic PC segmentation. We applied automated PC volumetry to patients with unilateral temporal lobe epilepsy with hippocampal sclerosis (TLE; n = 174 including n = 58 controls) and to the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n = 151, of whom with mild cognitive impairment (MCI), n = 71; Alzheimer's disease (AD), n = 33; controls, n = 47). In controls, mean PC volume was 485 mm3 on the right and 461 mm3 on the left. Automatic and manual segmentations overlapped with a Jaccard coefficient (intersection/union) of ~0.5 and a mean absolute volume difference of ~22 mm3 in healthy controls, ~0.40/ ~28 mm3 in patients with TLE, and ~ 0.34/~29 mm3 in patients with AD. In patients with TLE, PC atrophy lateralised to the side of hippocampal sclerosis (p < .001). In patients with MCI and AD, PC volumes were lower than those of controls bilaterally (p < .001). Overall, we have validated automatic PC volumetry in healthy controls and two types of pathology. The novel finding of early atrophy of PC at the stage of MCI possibly adds a novel biomarker. PC volumetry can now be applied at scale.
Every individual makes a difference: A trinity derived from linking individual brain morphometry, connectivity and mentalising ability
Authors: Li Zhaoning , Dong Qunxi , Hu Bin , Wu Haiyan
Published: April 2023

Mentalising ability, indexed as the ability to understand others' beliefs, feelings, intentions, thoughts and traits, is a pivotal and fundamental component of human social cognition. However, considering the multifaceted nature of mentalising ability, little research has focused on characterising individual differences in different mentalising components. And even less research has been devoted to investigating how the variance in the structural and functional patterns of the amygdala and hippocampus, two vital subcortical regions of the “social brain”, are related to inter‐individual variability in mentalising ability. Here, as a first step toward filling these gaps, we exploited inter‐subject representational similarity analysis (IS‐RSA) to assess relationships between amygdala and hippocampal morphometry (surface‐based multivariate morphometry statistics, MMS), connectivity (resting‐state functional connectivity, rs‐FC) and mentalising ability (interactive mentalisation questionnaire [IMQ] scores) across the participants (). In IS‐RSA, we proposed a novel pipeline, that is, computing patching and pooling operations‐based surface distance (CPP‐SD), to obtain a decent representation for high‐dimensional MMS data. On this basis, we found significant correlations (i.e., second‐order isomorphisms) between these three distinct modalities, indicating that a trinity existed in idiosyncratic patterns of brain morphometry, connectivity and mentalising ability. Notably, a region‐related mentalising specificity emerged from these associations: self‐self and self‐other mentalisation are more related to the hippocampus, while other‐self mentalisation shows a closer link with the amygdala. Furthermore, by utilising the dyadic regression analysis, we observed significant interactions such that subject pairs with similar morphometry had even greater mentalising similarity if they were also similar in rs‐FC. Altogether, we demonstrated the feasibility and illustrated the promise of using IS‐RSA to study individual differences, deepening our understanding of how individual brains give rise to their mentalising abilities.
Manifestation of pityriasis rosea and pityriasis rosea‐like eruptions after Covid‐19 vaccine: A systematic review
Authors: Khan Iman , Elsanousi Ahmed A. , Shareef Amena M. , Tebha Sameer S. , Arif Aabiya , Gul Sana
Published: April 2023

Background: After introducing Covid‐19 vaccines, a few side effects were reported, pityriasis rosea being one of them. Therefore, this study will systematically review its manifestation afteradministration.Methods: Databases were searched, covering a timeline from December 1, 2019 to February 28, 2022. Data were independently extracted and accessed for bias. SPSS statistical software version 25 was used for appropriate inferential statistics. Results: Thirty‐one studies were included for data extraction after screening following the eligibility criteria. A total of 111 people were identified to have developed pityriasis rosea or pityriasis rosea‐like eruptions after vaccination, out of which 36 (55.38%) were female. The average age of incidence was calculated to be 44.92 years, and 63 (62.37%) people presented after administration of the first dose. It was found popularly in the trunk area, either asymptomatically or with mild symptoms. Meantime the onset, was 8.58 days, and meantime it took to recover, was 6.44 weeks. Conclusion: The association between pityriasis rosea and pityriasis rosea‐like eruptions after Covid‐19 vaccines was established, but given the scarcity of studies, there is a need to conduct different clinical trials to confirm this association further and study the etiology and mechanism of the disease.
Organ‐based clues for diagnosis of inborn errors of immunity: A practical guide for clinicians
Authors: Mohammadi Fatemeh , Yadegar Amirhossein , Mardani Mahta , Ayati Aryan , Abolhassani Hassan , Rezaei Nima
Published: April 2023

Inborn errors of immunity (IEI) comprise a group of about 490 genetic disorders that lead to aberrant functioning or the development of distinct immune system components. So far, a broad spectrum of IEI‐related manifestations has been noted in the literature. Due to overlapping signs and symptoms of IEI, physicians face challenges in appropriately diagnosing and managing affected individuals. The last decade has witnesses improving in the molecular diagnosis of IEI patients. As a result, it can be the mainstay of diagnostic algorithms, prognosis, and possibly therapeutic interventions in patients with IEI. Furthermore, reviewing IEI clinical complications demonstrates that the manifestations and severity of the symptoms depend on the involved gene that causes the disease and its penetrance. Although several diagnostic criteria have been used for IEI, not every patient can be explored in the same way. As a result of the failure to consider IEI diagnosis and the variety of diagnostic capabilities and laboratory facilities in different regions, undiagnosed patients are increasing. On the other hand, early diagnosis is an almost essential element in improving the quality of life in IEI patients. Since there is no appropriate guideline for IEI diagnosis in different organs, focusing on the clues in the patient's chief complaint and physical exams can help physicians narrow their differential diagnosis. This article aims to provide a practical guide for IEI diagnosis based on the involved organ. We hope to assist clinicians in keeping IEI diagnosis in mind and minimizing possible related complications due to delayed diagnosis.
Network pharmacology and molecular docking analysis on the mechanism of Cordyceps militaris polysaccharide regulating immunity through TLR4/TNF‐α pathwayss
Authors: Pei Hongyan , He Zhongmei , Chen Weijia , Zhao Yan , Li Jianming , Wang Ruibing , Zong Ying , Du Rui
Published: April 2023

The role of polysaccharide components in the immune system, especially immunomodulatory effects, has received increasing attention. In this context, in this study, network pharmacology was adopted to explore the hypothesis of a multitarget mechanism for immune modulation by Chrysalis polysaccharides. A total of 174 common targets were screened by network pharmacology, with the main ones being TNF, MAPK3, CASP3, VEGFA, and STAT3, mostly enriched in the Toll pathway. The molecular docking results showed that the polysaccharide fraction of Chrysalis binds well to TNF proteins. Besides, in vitro cellular assays were performed to verify the ability of Chrysalis polysaccharides to regulate macrophage polarization and to screen for macrophage surface receptors. Furthermore, in vivo experiments were conducted to prove the activation of TLR4 and TNF‐α protein expression in mice by Chrysalis polysaccharide.
Novel differential calcium regulation of hematopoietic stem and progenitor cells under physiological low oxygen conditions
Authors: Dausinas Ni Paige , Hartman Melissa , Slack Jacob , Basile Christopher , Liu Sheng , Wan Jun , O'Leary Heather A.
Published: April 2023

Low oxygen bone marrow (BM) niches (~1%–4% low O2) provide critical signals for hematopoietic stem/progenitor cells (HSC/HSPCs). Our presented data are the first to investigate live, sorted HSC/HSPCs in their native low O2 conditions. Transcriptional and proteomic analysis uncovered differential Ca2+ regulation that correlated with overlapping phenotypic populations consisting of robust increases of cytosolic and mitochondrial Ca2+, ABC transporter (ABCG2) expression and sodium/hydrogen exchanger (NHE1) expression in live, HSC/HSPCs remaining in constant low O2. We identified a novel Ca2+ high population in HSPCs predominantly detected in low O2 that displayed enhanced frequency of phenotypic LSK/LSKCD150 in low O2 replating assays compared to Ca2+ low populations. Inhibition of the Ca2+ regulator NHE1 (Cariporide) resulted in attenuation of both the low O2 induced Ca2+ high population and subsequent enhanced maintenance of phenotypic LSK and LSKCD150 during low O2 replating. These data reveal multiple levels of differential Ca2+ regulation in low O2 resulting in phenotypic, signaling, and functional consequences in HSC/HSPCs.
Lactobacillus plantarum postbiotics trigger AMPK‐dependent autophagy to suppress Salmonella intracellular infection and NLRP3 inflammasome activation
Authors: Wu Yanping , Hu Aixin , Shu Xin , Huang Wenxia , Zhang Ruiqiang , Xu Yinglei , Yang Caimei
Published: April 2023

We previously found that Lactobacillus plantarum (LP)‐derived postbiotics protected animals against Salmonella infection, but the molecular mechanism remains obscure. This study clarified the mechanisms from the perspective of autophagy. Intestinal porcine epithelial cells (IPEC‐J2) were pretreated with LP‐derived postbiotics (the culture supernatant, LPC; or heat‐killed bacteria, LPB), and then challenged with Salmonella enterica Typhimurium (ST). Results showed that LP postbiotics markedly triggered autophagy under ST infection, as indicated by the increased LC3 and Beclin1 and the decreased p62 levels. Meanwhile, LP postbiotics (particularly LPC) exhibited a strong capacity of inhibiting ST adhesion, invasion and replication. Pretreatment with the autophagy inhibitor 3‐methyladenine (3‐MA) led to a significant decrease of autophagy and the aggravated infection, indicating the importance of autophagy in LP postbiotics‐mediated Salmonella elimination. LP postbiotics (especially LPB) significantly suppressed ST‐induced inflammation by modulating inflammatory cytokines (the increased interleukin (IL)‐4 and IL‐10, and decreased tumor necrosis factor‐α (TNF), IL‐1β, IL‐6 and IL‐18). Furthermore, LP postbiotics inhibited NOD‐like receptor protein 3 (NLRP3) inflammasome activation, as evidenced by the decreased levels of NLRP3, Caspase‐1 and apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC). Deficits in autophagy resulted in an increase of inflammatory response and inflammasome activation. Finally, we found that both LPC and LPB triggered AMP‐activated protein kinase (AMPK) signaling pathway to induce autophagy, and this was further confirmed by AMPK RNA interference. The intracellular infection and NLRP3 inflammasome were aggravated after AMPK knockdown. In summary, LP postbiotics trigger AMPK‐mediated autophagy to suppress Salmonella intracellular infection and NLRP3 inflammasome in IPEC‐J2 cells. Our findings highlight the effectiveness of postbiotics, and provide a new strategy for preventing Salmonella infection.
Limits of the thermal tolerance of two lentic crustaceans: The role of lactate dehydrogenase
Authors: Zeis Bettina , Koch Marita , Gigengack Ulrike , Morawe Tobias , Paul Rüdiger J.
Published: April 2023

Limits of thermal tolerance in animal life is dependent on energy supply. Accordingly, the lowered ATP production capacity in ectotherms at high temperatures, which arises from a mismatch between oxygen supply and demand and the consequent switch from aerobic to anaerobic metabolism, affects the thermal resistance of these animals. The anaerobic ATP production capacity depends on the functional properties of the enzymes that reduce pyruvate. Thus, the present study focused on the role of the lactate dehydrogenase (LDH) of two daphnid species for anaerobic energy production at warm temperatures and the implications for their specific heat tolerances. Daphnia magna showed a higher thermal limit (indicated by immobilization time at 37°C) than Daphnia pulex, and in both species, this limit increased with rising acclimation temperature. In contrast to D. pulex, D. magna accumulated significant amounts of lactate at higher ambient temperatures. The intensity of anaerobic metabolism was also affected by acclimation temperature. Studying the functional enzyme properties revealed altered maximal reaction rates and substrate inhibitions of the LDH suites of the two daphnid species. D. magna LDH showed a significantly lower substrate inhibition than D. pulex LDH. The LDH isoform composition and the temperature‐induced changes differed between both species. The detected qualitative modulations of the LDH suites may have resulted from differential isoform expression and different maturation processes. The species‐specific LDH characteristics imply a higher anaerobic energy production at warm temperatures in D. magna, which likely contributes to the higher heat tolerance of this species.
Initiative to reduce inappropriate venous thromboembolism prophylaxis in an 11‐hospital safety net system: An electronic health records‐based approach
Authors: Haller Matthew D. , Cho Hyung J. , Ahn Jennifer , Krouss Mona , Alaiev Daniel , Yoon Garrett H. , Dunn Andrew S. , Fagan Ian
Published: April 2023

Background

While pharmacologic prophylaxis has benefits for venous thromboembolism (VTE) prevention in high‐risk patients, unnecessary use carries potential harm, including bleeding, heparin‐induced thrombocytopenia, and patient discomfort, and should be avoided in low‐risk patients. While many quality improvement initiatives aim to reduce underuse, successful models on reducing overuse are sparse in the literature.

Objective

We aimed to create a quality improvement initiative to reduce overuse of pharmacologic VTE prophylaxis.

Designs, Settings and Participants

A quality improvement initiative was implemented across 11 safety net hospitals in New York City.

Intervention

The first electronic health record (EHR) intervention consisted of a VTE order panel that facilitated risk assessment and recommended VTE prophylaxis for high‐risk patients only. The second EHR intervention used a best practice advisory that alerted clinicians when prophylaxis was ordered for a patient previously deemed “low risk.” Prescribing rates were compared through a three‐segment interrupted time series linear regression design.

Results

Compared to the preintervention period, the first intervention did not change the rate of total pharmacologic prophylaxis immediately after implementation (1.7% relative change, p = .38) or over time (slope difference of 0.20 orders per 1000 patient days, p = .08). Compared to the first intervention period, the second intervention led to an immediate 4.5% reduction in total pharmacologic prophylaxis (p = .04) but increased thereafter (slope difference of 0.24, p = .03) such that weekly rates at the end of the study were similar to rates prior to the second intervention.
Multiparametric MRI of Solid Renal Masses: Principles and Applications of Advanced Quantitative and Functional Methods for Tumor Diagnosis and Characterization
Authors: Laothamatas Indira , Al Mubarak Haitham , Reddy Arthi , Wax Rebecca , Badani Ketan , Taouli Bachir , Bane Octavia , Lewis Sara
Published: April 2023

Solid renal masses (SRMs) are increasingly detected and encompass both benign and malignant masses, with renal cell carcinoma (RCC) being the most common malignant SRM. Most patients with SRMs will undergo management without a priori pathologic confirmation. There is an unmet need to noninvasively diagnose and characterize RCCs, as significant variability in clinical behavior is observed and a wide range of differing management options exist. Cross‐sectional imaging modalities, including magnetic resonance imaging (MRI), are increasingly used for SRM characterization. Multiparametric (mp) MRI techniques can provide insight into tumor biology by probing different physiologic/pathophysiologic processes noninvasively. These include sequences that probe tissue microstructure, including intravoxel incoherent motion diffusion‐weighted imaging (IVIM‐DWI) and T1 relaxometry; oxygen metabolism (blood oxygen level dependent [BOLD‐MRI]); as well as vascular flow and perfusion (dynamic contrast‐enhanced MRI [DCE‐MRI] and arterial spin labeling [ASL]). In this review, we will discuss each mpMRI method in terms of its principles, roles, and discuss the results of human studies for SRM assessment. Future validation of these methods may help to enable a personalized management approach for patients with SRM in the emerging era of precision medicine.

Evidence Level

5.

Technical Efficacy

2.