bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of Viscoelasticity and Flow Activation Energy in Biomolecular Condensates
Authors: Alshareedah Ibraheem , Singh Anurag , Quinn Alexander , Banerjee Priya R.
Published: December 2022

The form and function of biomolecular condensates, which are phase-separated intracellular granules of proteins and RNAs, are regulated by their material and dynamical properties. Emerging reports suggest that biomolecular condensates are viscoelastic network fluids, and the primary sequence and structure of the constituent biopolymers govern their bulk fluid phase properties. Here, we employ a multi-parametric approach to dissect the molecular determinants of condensate viscoelasticity by studying a series of condensates formed by engineered multivalent arginine-rich polypeptides and single-stranded DNA. By measuring the terminal relaxation time of the condensate network through optical tweezer-based microrheology and the activation energy of viscous flow through temperature-controlled video particle tracking, we show that condensate viscoelasticity is controlled by two distinct factors − sequence-encoded inter-chain interactions of associative polymers and entropic factors emerging from their intrinsic polymer properties such as the chain length. The biomolecular diffusion in the dense phase shows a strong dependence on the flow activation energy, indicating that the intra-condensate transport properties are primarily reaction-dominant. These results provide a glimpse of the multifaceted control of viscoelasticity and transport properties within biomolecular condensates. Flow activation energy measurement of single and multicomponent condensates by thermo-rheology provides a direct route to quantify inter-chain interactions in the dense phase and dissect the roles of chain entropy and valence in dictating the viscoelastic behavior of biomolecular condensates.
A Sensory-Motor Theory of the Neocortex based on Active Predictive Coding
Authors: Rao Rajesh P. N.
Published: December 2022

We propose that the neocortex implements active predictive coding (APC), a form of predictive coding that incorporates hierarchical dynamics and actions. In this model, each neocortical area estimates both sensory states and actions, and the cortex as whole learns to predict the sensory consequences of actions at multiple hierarchical levels. “Higher” cortical areas maintain more abstract representations at larger spatiotemporal scales compared to “lower” areas. Feedback from higher areas modulate the dynamics of both state and action networks in lower areas. This allows the cortical network to model the complex dynamics and physics of the world in terms of simpler compositional elements (state transition functions). Simultaneously, current higher level goals invoke sequences of lower level sub-goals and actions, allowing the network to solve complex planning problems by composing simpler solutions. Planning (“system 2” thinking) in turns allows the network to learn, over time, perception-to-action mappings (policies; “system 1” thinking) at multiple abstraction levels. We provide examples from simulations illustrating how the same APC architecture can solve problems that, at first blush, seem very different from each other: (1) how do we recognize an object and its parts using eye movements? (2) why does perception seem stable despite eye movements? (3) how do we learn compositional representations, e.g., part-whole hierarchies, and nested reference frames for equivariant vision? (4) how do we model the “physics” of a complex environment by decomposing it into simpler components? (5) how do we plan actions in a complex domain to achieve a goal by composing sequences of sub-goals and simpler actions? and (6) how do we form episodic memories of sensory-motor experiences? We propose a mapping of the APC network to the laminar architecture of the cortex and suggest possible roles for cortico-cortical, cortico-thalamic, cortico-hippocampal and cortico-subcortical pathways.
SAMBA: Structure-Learning of Aquaculture Microbiomes using a Bayesian Approach
Authors: Soriano Beatriz , Hafez Ahmed Ibrahem , Naya-Català Fernando , Moroni Federico , Moldovan Roxana Andreea , Toxqui-Rodríguez Socorro , Piazzon M. Carla , Arnau Vicente , Llorens Carlos , Pérez-Sánchez Jaume
Published: December 2022

In aquaculture systems, microbiomes of farmed fishes may contain thousands of bacterial taxa that establish complex networks of interactions among each other and among the host and the environment. Gut microbiomes in many fish species consist of thousands of bacterial taxa that interact among each other, their environment, and the host. These complex networks of interactions are regulated by a diverse range of factors, yet little is known about the hierarchy of these interactions. Here, we introduce SAMBA (Structure-Learning of Aquaculture Microbiomes using a Bayesian Approach), a computational tool that uses a unified Bayesian network approach to model the network structure of fish gut microbiomes and their interactions with biotic and abiotic variables associated with typical aquaculture systems. SAMBA accepts input data on microbial abundance from 16S rRNA amplicons as well as continuous and categorical information from distinct farming conditions. From this, SAMBA can create and train a network model scenario that can be used to: i) infer information how specific farming conditions influence the diversity of the gut microbiome or pan-microbiome, and ii) predict how the diversity and functional profile of that microbiome would change under other experimental variables. SAMBA also allows the user to visualize, manage, edit, and export the acyclic graph of the modelled network. Our study presents examples and test results of bayesian network scenarios created by SAMBA using data from: a) a microbial synthetic experiment; and b) the pan-microbiome of the gilthead sea bream (Sparus aurata) under different experimental feeding trials. It is worth noting that the usage of SAMBA is not limited to aquaculture systems and can be used for modelling microbiome-host network relationships in any vertebrate organism, including humans, in any system and/or ecosystem.
Functionally dissecting claustrum along anterior-posterior axis in anxiety and higher sensitivity to cocaine
Authors: Zhao Ziheng , Liu Zhaoyu , Chen Liying , Chen Wenwen , Guo Hao , Wang Jingjing , Mai Yuning , Wei Xiaoyan , Ding Jianhua , Ge Feifei , Fan Yu , Guan Xiaowei
Published: December 2022

Adolescent cocaine exposure (ACE) induce anxiety and higher sensitivity to drug addiction during adulthood. Here, we show that the claustrum is crucial for control of these two distinct psychiatric disorders in ACE mice. In the process of anxiety test, the CaMKII-positive neurons in median portion of claustrum (MClaustrum) were obviously triggered, and chemogenetic suppressing these neurons efficiently reduced ACE-induced anxiety in adulthood. While, the CaMKII-positive neurons in anterior portion of claustrum (AClaustrum) were obviously activated in response to cocaine-induced conditioned place preference (CPP), and chemogenetic suppressing these neurons efficiently blocked cocaine CPP in ACE mice during adulthood. Our findings dissociating specific sub-portions of claustrum for drug-related anxiety and susceptibility of addiction, extending our understanding to diverse functions of claustrum subregions.
The anti-platelet drug cilostazol enhances interrenal steroidogenesis and exerts a scant effect on innate immune responses in zebrafish
Authors: Chang Wei-Chun , Chen Mei-Jen , Chen Yu-Fu , Chou Chih-Wei , Chuang Yung-Jen , Liu Yi-Wen
Published: December 2022

Rationale

Cilostazol, an anti-platelet phosphodiesterase-3 inhibitor used for the treatment of intermittent claudication, is known for its pleiotropic effects on platelets, endothelial cells and smooth muscle cells. However, how cilostazol impacts the endocrine system and the injury-induced inflammatory processes remains unclear.

Methods

We used the zebrafish, a simple transparent model that demonstrates rapid development and a strong regenerative ability, to test whether cilostazol influences steroidogenesis, and the temporal and dosage effects of cilostazol on innate immune cells during tissue damage and repair.

Results

While dosages of cilostazol from 10 to 100 μM did not induce any noticeable morphological abnormality in the embryonic and larval zebrafish, the heart rate and adrenal/interrenal steroidogenesis in larval zebrafish was increased in a dose-dependent manner. During larval fin amputation and regeneration, cilostazol treatments did not affect the immediate injury-induced recruitment of either neutrophils or macrophages, followed by a subtle yet significant effect on reducing the neutrophil retention at the lesion site.

Conclusions

Our results indicate that cilostazol has a significant effect on the growth and endocrine function of steroidogenic tissue; and a limited effect on the neutrophil retention without affecting neutrophil and macrophage recruitment during tissue damage and repair.
Ancestral protein reconstruction reveals evolutionary events governing variation in Dicer helicase function
Authors: Aderounmu Adedeji M. , Aruscavage P. Joseph , Kolaczkowski Bryan , Bass Brenda L.
Published: December 2022

Antiviral defense in ecdysozoan invertebrates requires Dicer with a helicase domain capable of ATP hydrolysis. But despite well-conserved ATPase motifs, human Dicer is incapable of ATP hydrolysis, consistent with a muted role in antiviral defense. To investigate this enigma, we used ancestral protein reconstruction to resurrect Dicer’s helicase in animals and trace the evolutionary trajectory of ATP hydrolysis. Biochemical assays indicated ancient Dicer possessed ATPase function, that like extant invertebrate Dicers, is stimulated by dsRNA. Analyses revealed that dsRNA stimulates ATPase activity by increasing ATP affinity, reflected in Michaelis constants. Deuterostome Dicer-1 ancestor, while exhibiting lower dsRNA affinity, retained ATPase activity; importantly, ATPase activity was undetectable in the vertebrate Dicer-1 ancestor, which had even lower dsRNA affinity. Reverting residues in the ATP hydrolysis pocket was insufficient to rescue hydrolysis, but including additional substitutions distant from the ATPase pocket rescued vertebrate Dicer-1’s ATPase function. Our work suggests Dicer lost ATPase function in the vertebrate ancestor due to loss of ATP affinity, involving motifs distant from the active site, important for coupling dsRNA binding to the active conformation. RLRs important for interferon signaling, and their competition with Dicer for viral dsRNAs, possibly provided incentive to jettison an active helicase in vertebrate Dicer.
Phenotypical Rescue of Bmp15 Deficiency by Mutation of Inhibinα(inha) Provides Novel Clues to How Bmp15 Controls Zebrafish Folliculogenesis
Authors: Zhai Yue , Zhao Cheng , Geng Ruijing , Wu Kun , Yuan Mingzhe , Ai Nana , Ge Wei
Published: December 2022

As an oocyte-specific growth factor, bone morphogenetic protein 15 (BMP15) plays a critical role in controlling folliculogenesis. However, the mechanism of BMP15 action remains elusive. Using zebrafish as the model, we created abmp15mutant using CRISPR/Cas9 and demonstrated thatbmp15deficiency caused a significant delay in follicle activation and puberty onset followed by complete arrest of follicle development at previtellogenic stage without yolk accumulation. The mutant females eventually underwent female-to-male sex reversal to become functional males, which was accompanied by a series of changes in secondary sexual characteristics. Interestingly, the blockade of folliculogenesis and sex reversal inbmp15mutant could be rescued by the loss of inhibin (inha-/-). The follicles of double mutant (bmp15-/-;inha-/-) could progress to mid-vitellogenic stage with yolk accumulation and the fish maintained their femaleness without sex reversal. Transcriptome analysis revealed up-regulation of pathways related to TGF-β signaling and endocytosis in the double mutant follicles. Intriguingly, the expression of inhibin/activin βAa subunit (inhbaa) increased significantly in the double mutant ovary. Further knockout ofinhbaain the triple mutant (bmp15-/-;inha-/-;inhbaa-/-) resulted in the loss of yolk granules again in the oocytes although the follicles could continue to grow beyond the size range of previtellogenic stage. The serum levels of estradiol (E2) and vitellogenin (Vtg) both decreased significantly inbmp15single mutant females, returned to normal in the double mutant (bmp15-/-;inha-/-), but reduced again significantly in the triple mutant (bmp15-/-;inha-/-;inhbaa-/-). E2 treatment could rescue the vitellogenic follicles inbmp15-/-, and fadrozole (a nonsteroidal aromatase inhibitor) treatment blocked yolk accumulation inbmp15-/-;inha-/-fish. In summary, the present study provided comprehensive genetic evidence for the interaction ofbmp15pathways and the activin-inhibin system in regulating folliculogenesis, in particular E2 production from the follicle, Vtg biosynthesis in the liver and its update by the developing oocytes.
Behavioral responses of free flyingDrosophila melanogasterto shiny, reflecting surfaces
Authors: Mathejczyk Thomas , Babo Edouard J. , Schönlein Erik , Grinda Nikolai V. , Greiner Andreas , Okrožnik Nina , Belušič Gregor , Wernet Mathias F.
Published: December 2022

Active locomotion plays an important role in the life of many animals since it permits to explore the environment and find vital resources. Most insect species rely on a combination of visual cues such as celestial bodies, landmarks, or linearly polarized light to navigate or to orient themselves in their surroundings. In nature, linearly polarized light can arise either from atmospheric scattering or from reflections off shiny non-metallic surfaces like water or shiny foil. Although multiple reports described different behavioral responses of various insects to such shiny surfaces, little is known about the retinal detectors or the underlying neural circuits. Our goal was to quantify the behavioral responses of free flyingDrosophila melanogaster, a molecular genetic model organism that allows for systematic dissection of neural circuitry. Fruit flies were placed in a custom-built arena with controlled environmental parameters (temperature, humidity, and light intensity). Flight densities and landings were quantified for hydrated and dehydrated fly populations when separately exposed to three different stimuli such as a diffusely-reflecting matt plate, a small patch of shiny foil, versus real water. Our analysis reveals for the first time that flying fruit flies indeed use vision to guide their flight maneuvers around shiny surfaces.
Brain Electrical Bioactivity Informational Specifics in Relation to Behavioural and Cognitive Functions in Children with Learning Difficulties
Authors: Tolmacha Nelli , Pudvosky Konstantin , Vandans Janis , Bondarenko Andrey
Published: December 2022

Annotation

The current paper performs a comprehensive assessment of electroencephalogram (EEG) parameters and features of cognitive functions of the brain in children of preschool (6-7) and primary school age (7-8) years with learning difficulties are considered. Spectral and coherent EEG analysis is conducted as well as particularities of gamified orientation in the maze. Spectral analysis of the EEG in children with learning difficulties revealed a speed decrease in the formation of almost all indicators of alpha activity and an increase in the power of slow-wave activity in the EEG, which was more pronounced in the left hemisphere of the brain. EEG coherence analysis revealed early differences in the spatial organization of the coherence function both in EEG rhythms and the cerebral hemispheres. A high level of motor activity in the maze, fragmented perception, unstable attention, low volume of operational memory, and poor optimization of skills in mastering a new space in children with learning difficulties correlated with indicators of age-related neurophysiological immaturity in terms of EEG.
Structural basis for the mechanism and antagonism of receptor signaling mediated by Interleukin-9 (IL-9)
Authors: De Vos Tatjana , Godar Marie , Bick Fabian , Papageorgiou Anna C. , Evangelidis Thomas , Marković Iva , Mortier Eva , Dumoutier Laure , Tripsianes Konstantinos , Blanchetot Christophe , Savvides Savvas N.
Published: December 2022

Interleukin-9 (IL-9) is the hallmark cytokine in Th9 immunity and is also central to Innate Lymphocyte 2 (ILC2) biology. Furthermore, receptor signaling mediated by IL-9 has been linked to inflammatory and autoimmune diseases, and cancer. Despite its functional pleiotropy, the structure-function landscape of IL-9 had remained enigmatic. Here, we show via a combination of X-ray crystallography and NMR that human IL-9 adopts a helical bundle fold with unprecedented structural features among helical cytokines, including five disulfide bridges. Binding of IL-9 to the interdomain junction of IL-9Rα results in marked structural changes on the opposite face of IL-9 that prime the binary complex for recruiting the common gamma chain (γc) for signaling. Surprisingly, this tripartite cytokine-receptor assembly displays a markedly lower affinity than the IL-9: IL-9Rα complex, which we trace to distinct features of IL-9Rα that might destabilize the ternary complex. Furthermore, we developed monoclonal antibodies that antagonize IL-9 activity by sterically competing for the binding footprint of IL-9Rα. Collectively, we here provide a structural and mechanistic blueprint to facilitate interrogation and modulation of pleiotropic signaling outputs of IL-9 in physiology and disease.
Temporal Regulation of Organelle Biogenesis
Authors: Dixit Smruti , Aniruddha N , Choubey Sandeep
Published: December 2022

Organelle abundance is tightly regulated in eukaryotic cells in response to external stimuli. The underlying mechanisms responsible for this regulation remains less understood. Time-lapse imaging of fluorescently labelled organelles allow for counting individual organelle copies at a single-cell level. These experiments contain information about the time evolution of distribution of organelle number across a population of cells. To tap onto such data, we build upon a recently proposed kinetic model of organelle biogenesis that explicitly incorporates de novo synthesis, fission, fusion and degradation of organelles. Different limits of this general model correspond to distinct mechanisms of organelle biogenesis. We compute the first two moments of organelle number distribution for these different mechanisms. Interestingly, different mechanisms of biogenesis lead to qualitatively distinct temporal behavior of cell-to-cell variability (noise), thereby allowing us to discern between these mechanisms. Notably, noise in temporal organelle abundance exhibits strikingly more complex behaviour as compared to the steady state. Our modeling framework paves the way for extracting quantitative information about the dynamics of organelle biogenesis from time-lapse experiments that can measure organelle abundance at single-molecule resolution.
Acidophilic nitrification alleviates phosphorus deficiency in hydroponics using biogas digestates
Authors: Sakuma Satoru , Endo Ryosuke , Shibuya Toshio
Published: December 2022

Biogas digestates can be applied to hydroponics via nitrification. However, the low solubility of phosphorus in digestates can cause phosphorus deficiency in plants. Here, we hypothesized that acidophilic nitrification might prevent this deficiency by dissolving phosphorus in the digestate. Acidophilic and neutrophilic nitrification were conducted at a pH of 3.27 and 6.25 using biogas digestates from food wastes. Acidophilic nitrification dissolved about 3.5 times more phosphorus than neutrophilic nitrification, but the increased acidity also reduced the nitrification rate, resulting in residual ammonium. We then grew lettuce hydroponically with filtrates of these digestates. The growth performance suggested that the increased phosphorus improved growth and that the residual ammonium did not inhibit it. Acidophilic nitrification was shown to be effective for use in hydroponics, particularly to alleviate phosphorus deficiency. These findings should provide new insights into resource recycling, which is essential in both urban and space environments.

Graphical abstract
Aedes aegyptieggs use rewired polyamine and lipid metabolism to survive extreme desiccation
Authors: Prasad Anjana , Sreedharan Sreesa , Bakthavachalu Baskar , Laxman Sunil
Published: December 2022

Upon extreme water loss, some organisms pause their life cycles and escape death, in a process called anhydrobiosis. While widespread in microbes, this is uncommon in animals. Mosquitoes of theAedesgenus are vectors for several viral diseases in humans. These mosquitoes lay eggs that survive extreme desiccation and this property greatly enhances geographical expansion of these insects. The molecular principles of egg survival and hatching post-desiccation in these insects remain obscure. In this report, we find that eggs ofAedes aegypti, in contrast to those ofAnopheles stephensi, are true anhydrobiotes.Aedesembryos acquire desiccation tolerance at a late developmental stage. We uncover unique proteome-level changes inAedesembryos during desiccation. These changes reflect a metabolic state with reduced central carbon metabolism, and precise rewiring towards polyamine production, altered lipid levels and enhanced lipid utilization for energy. Using inhibitor-based approaches targeting these processes in blood-fed mosquitoes that lay eggs, we infer a two-step process of anhydrobiosis inAedeseggs, where polyamine accumulation as well as lipid breakdown confer desiccation tolerance, and rapid lipid breakdown fuels energetic requirements enabling the revival of mosquito larvae post rehydration.
Intra- and inter-species interactions drive early phases of invasion in mice gut microbiota
Authors: Gencel Melis , Cofino Gisela Marrero , Hui Cang , Sahaf Zahra , Gauthier Louis , Tsang Derek , Philpott Dana , Ramathan Sheela , Menendez Alfredo , Bershtein Shimon , Serohijos Adrian W.R.
Published: December 2022

The stability and dynamics of ecological communities are dictated by interaction networks typically quantified at the level of species.1–10But how such networks are influenced by intra-species variation (ISV) is poorly understood.11–14Here, we use ~500,000 chromosomal barcodes to track high-resolution intra-species clonal lineages ofEscherichia coliinvading mice gut with the increasing complexity of gut microbiome: germ-free, antibiotic-perturbed, and innate microbiota. By co-clustering the dynamics of intra-species clonal lineages and those of gut bacteria from 16S rRNA profiling, we show the emergence of complex time-dependent interactions betweenE. coliclones and resident gut bacteria. With a new approach, dynamic covariance mapping (DCM), we differentiate three phases of invasion in susceptible communities: 1) initial loss of community stability asE. colienters; 2) recolonization of some gut bacteria; and 3) recovery of stability withE. colicoexisting with resident bacteria in a quasi-steady state. Comparison of the dynamics, stability and fitness from experimental replicates and different cohorts suggest that phase 1 is driven by mutations inE. colibefore colonization, while phase 3 is byde novomutations. Our results highlight the transient nature of interaction networks in microbiomes driven by the persistent coupling of ecological and evolutionary dynamics.

One-Sentence Summary

High-resolution lineage tracking and dynamic covariance mapping (DCM) define three distinct phases during early gut microbiome invasion.
Neurological Disorder after Severe Pneumonia is Associated with Translocation of Bacteria from Lung to Brain
Authors: Ma Qingle , Yao Chenlu , Wu Yi , Wang Heng , Fan Qin , Yang Qianyu , Xu Jialu , Dai Huaxing , Zhang Yue , Xu Fang , Lu Ting , Wang Chao
Published: December 2022

The neurological disorder is a common feature in patients who recovered from severe acute pneumonia. However, the underline mechanisms remain not very clear. Here we show that these neurological syndromes after severe acute pneumonia are partly attributed to the translocation of bacteria from the lung to the brain during pneumonia. We detected an emerging and increased bacteria in the brain tissue of mice with lipopolysaccharide-induced experimental severe pneumonia. Interestingly, using 16S rDNA amplification sequencing, similarities were found between the brain’s flora species and those of the lungs, indicating the bacteria in the brain may originate from the lung. We also observed the impairment of the lung-blood barrier and brain-blood barrier, simultaneously, allowing lung bacteria invade the brain during pneumonia. An elevated microglia and astrocytes activation signature through bacterial infection-related pathways is observed by single-cell RNA sequencing, indicating a bacteria-induced disruption of brain homeostasis. Rapamycin delivered by platelet-derived extracellular vesicles provides an effective strategy to rescue the dysfunction of microglia and astrocytes, and relief neurological disorders. Collectively, we identify lung bacteria that play a role in altering brain homeostasis, which provides new insight into the mechanism of neurological syndromes after severe pneumonia.
Metformin antiproliferative activity is exclusively mediated by the membrane functional expression of the Chloride Intracellular Channel 1 in glioblastoma stem cells
Authors: Verduci Ivan , Cianci Francesca , Cazzoli Riccardo , Cannavale Gaetano , Veronesi Marina , Balboni Beatrice , Ranucci Matteo , Palloni Luca Maria Giovanni , Richichi Cristina , Faletti Stefania , Osti Daniela , Ailuno Giorgia , Caviglioli Gabriele , Tacconi Carlotta , Girotto Stefania , Barbieri Federica , Fantin Alessandro , Cavalli Andrea , Pelicci Giuliana , Florio Tullio , Minucci Saverio , Mazzanti Michele
Published: December 2022

Metformin is the first-line drug for type-2 diabetes. Retrospective analyses, based on diabetic patients’ clinical data, demonstrate that daily assumption of metformin reduces the incidence of several kinds of solid tumors. Even though it is widely agreed that metformin must be internalized to accomplish its pharmacological activity, direct evidence about metformin membrane permeability and/or the presence of a specific membrane receptor in cancer cells is still missing. Here, we show that the transmembrane form of Chloride Intracellular Channel 1 (tmCLIC1) works as a privileged metformin receptor in glioblastoma stem-like cells. We found that metformin impairs tmCLIC1 activity by a specific binding coordinated by arginine 29. Its mutation, preventing metformin to bind and block tmCLIC1, abolishes the biguanide inhibition of glioblastoma cell proliferation in 2D and 3D models and metformin dependent effect on mitochondrial respiration. In addition, we demonstrate the direct binding between the drug and its target, and byin vivoexperiments on zebrafish embryos and mice orthotopically engrafted with glioblastoma cells and treated with metformin, we prove that metformin binding to tmCLIC1 is crucial for metformin antineoplastic effect. Considering tmCLIC1’s contribution to glioblastoma progression, the present work provides the fundaments for future development of strategies aimed at improving metformin-tmCLIC1 interaction to further increase metformin therapeutic potential.
The informativeness of the top holdings of Chinese equity mutual funds
Authors: Yao Shuyi , Zhang Jianing
Published: December 2022

Purpose

This study aims to determine whether the stock holdings of equity mutual funds are informative for predicting future stock performance in the Chinese market. It is a puzzle that actively managed mutual funds underperform passive benchmarks, whereas retail investors still delegate investment decisions to the fund managers. The present study sheds light on whether mutual fund managers possess security selection skills in their top ten holdings.

Design/methodology/approach

By regression analysis and portfolio sorting, this study focuses on 830 Chinese A-share stocks in the industry research reports from the Guotai Junan Securities Company. It collects mutual fund's top ten holdings data from the Wind Financial Terminal between 2019Q1 and 2021Q1. As robustness checks, the result holds for the fixed-effect model, an additional measure of ranks in the top ten holdings, the predictability test based on the confusion matrix and two stage least square (2SLS) regression.

Findings

The authors find that the top ten holdings by equity mutual funds are informative for predicting stock performance and can provide valuable information for investors to support their decision-making.

Practical implications

The findings of this study provide insightful guidance for retail investors in making investment decisions and support the hypothesis that active fund management adds value.

Originality/value

Firstly, the authors find that the top ten holdings of Chinese mutual funds show significantly positive signals for future stock excess returns, indicating the selection skills of fund managers. Secondly, the above positive relationship exhibits a diminishing marginal effect with more funds holding this stock. Thirdly, the authors find that the predictability horizon of the number of overweighing funds is up to three quarters and then diminishes in the fourth quarter. Finally, investors have a 59% prediction accuracy for the whole stock sample and an 85% precision conditional on the predicted positive subsample to outperform the market. The authors also address the endogeneity and reverse causality issues.
Erythema multiforme associated with cancer radiotherapy: A single‐institution case series and literature review
Authors: Tanaka Nanako , Nakatani Shoko , Yahiro Chisato , Takai Toshihiro
Published: December 2022

Radiation dermatitis, limited to the irradiated site, is the most common cutaneous adverse reaction due to radiotherapy. There are scattered reports of erythema multiforme‐like rash, Stevens–Johnson syndrome, and toxic epidermal necrolysis associated with radiotherapy. Some of these reports include cases without remarkable drug history, which suggests rashes induced by radiotherapy. The lack of a large cohort study, however, makes it difficult to ascertain the time course, severity, and outcome of the cases. We aimed to evaluate the potential association between radiotherapy and erythema multiforme‐like rash in a larger sample of patients. We examined the records of patients at our institute who received radiotherapy and developed a rash from 2010 to 2021. We present 30 patients with erythema multiforme‐like rash, which arose during or after radiotherapy. We describe the background, details of radiotherapy, and clinical course of the patients including the cutaneous and extracutaneous symptoms. Radiotherapy was the most likely cause of rash, and in most cases, the rash was relieved by conservative management and radiation could be continued. When erythema multiforme‐like rash arises in patients under cancer treatment, radiotherapy should be considered a potential trigger.
The development of lipoprotein apheresis in Saxony in the last years
Authors: Kuss Solveig Frieda Rosa , Schatz Ulrike , Tselmin Sergey , Fischer Sabine , Julius Ulrich
Published: December 2022

Methods

Three hundred thirty‐nine patients (230 men, 109 women) treated with lipoprotein apheresis in Saxony, Germany, in 2018 are described in terms of age, lipid pattern, risk factors, cardiovascular events, medication, and number of new admissions since 2014, and the data are compared with figures from 2010 to 2013.

Results

Patients were treated by 45.5 physicians in 16 lipoprotein apheresis centers. With about 10 patients per 100 000 inhabitants, the number of patients treated with lipoprotein apheresis in Saxony is twice as high as in Germany as a whole. The median treatment time was 3 years. Almost all patients had hypertension; type 2 diabetes mellitus was seen significantly more often in patients with low Lipoprotein(a). Cardiovascular events occurred in almost all patients before initiation of lipoprotein apheresis, under apheresis therapy the cardiovascular events rate was very low in this high‐risk group. For some cardiovascular regions even no events could be observed.

Conclusions

The importance of lipoprotein apheresis in Saxony had been increasing from 2010 to 2018.
Multiple joint dislocations and bone disintegration in rheumatoid arthritis: A case report
Authors: Yuan Xuemei , Luo Feng , Li Chunxiang , Hong Xiong , Ma WuKai , Yao Xueming
Published: December 2022

Rheumatoid arthritis (RA) is a chronic inflammatory disease, which typically affects the small joints of the hands and feet. Anti‐rheumatism drugs should be promptly administered upon a diagnosis. Without standardized treatment, patients are prone to different degrees of deformities in the later stages of disease development, which negatively impact quality of life. We here report a case of a 52‐year‐old woman with an 18‐year history of RA. After intermittent immunotherapy with anti‐rheumatism drugs, the patient presented with multiple joint pain, dislocation, and disintegration of the bone. The interphalangeal joints of both hands were deformed to varying degrees and movement was significantly limited. After anti‐rheumatism treatment, the patient experienced reduced joint pain. This case should enhance understanding and serve as a guide for patient management toward the prevention of joint deformities caused by RA.
Fourteen‐year trends in the prescribing patterns of pediatric bipolar patients discharged from two public mental hospitals in Taiwan
Authors: Lin Ching‐Hua , Chan Hung‐Yu , Lin Hsin‐Yi , Chen Cheng‐Chung
Published: December 2022

Introduction

The management of pediatric bipolar disorder (PBD) requires pharmacotherapy to control acute symptoms, reduce relapse, prevent suicide, and improve psychosocial functioning. The purpose of this study was to investigate prescribing patterns among PBD patients discharged from two public mental hospitals in Taiwan, from 2006 to 2019.

Methods

PBD patients discharged from the two study hospitals, from 1 January 2006 to 31 December 2019 (n = 420), were included in the analysis. Prescribed drugs at discharge, including mood stabilizers (i.e., lithium, valproate, carbamazepine, and lamotrigine), antipsychotics (i.e., second‐ and first‐generation antipsychotics, SGAs and FGAs), and antidepressants, were explored. Complex polypharmacy was defined as the use of 3 or more agents among the prescribed drugs. Time trends of each prescribing pattern were analyzed using the Cochran‐Armitage Trend test.

Results

The most commonly prescribed psychotropic agents were SGAs (76.0%), followed by valproate (65.7%) and FGAs (24.8%). The prescription rates of SGAs, antidepressants, antidepressant plus antipsychotic, and antidepressant without mood stabilizer significantly increased over time, whereas the prescription rates of mood stabilizers, lithium, and FGAs significantly decreased.

Discussions

Prescribing patterns changed greatly for PBD patients over time. However, much more evidence supporting the effectiveness of psychotropic agents in PBD patients is required.
Bortezomib inhibits hepatocellular carcinoma via the Hippo‐Yes‐associated protein signalling pathway
Authors: Liao Yu , Hu Kejun , Liu Wangwang , Wang Wei , Qiu Huanhuan , Pan Shumin , Lv Qi , Xu Guanglin
Published: December 2022

Hepatocellular carcinoma (HCC) is one of the principle causes of cancer‐associated death throughout the world. However, the patients with HCC are insensitive to traditional drugs and lack effective therapeutic drugs. Dysregulation of Hippo‐Yes‐associated protein (YAP) signalling is closely associated with HCC. Bortezomib (BTZ) is mainly used in clinical multiple myeloma. It has recently been confirmed that BTZ could suppress cell proliferation in many different types of cancer. Nevertheless, the precise effects of BTZ on HCC and its possible interactions with the Hippo‐YAP signalling pathway in HCC cells remain largely unknown. In this study, HCC cell lines (HepG2 and Huh7) and nude mice with xenograft tumours were used to evaluate the influences of BTZ. Furthermore, we focused on exploring whether BTZ exerts its anti‐HCC effect through the Hippo‐YAP signalling pathway and aimed to lay a theoretical foundation for BTZ as a potential therapeutic drug for HCC. Herein, our results disclose a new mechanism of BTZ in controlling the cell growth of HCC. BTZ downregulates the level of YAP by promoting LATS1 expression to inhibit the growth of HCC cells, which leads to the phosphorylation of YAP and limits YAP nuclear translocation. In sum, our data confirmed that the Hippo‐YAP signalling pathway mediates the anti‐HCC effects of BTZ.
Canada's GBA+ framework in a (post)pandemic world: Issues, tensions and paths forward
Authors: Cameron Anna I. , Tedds Lindsay M.
Published: December 2022

This article traces the theoretical foundations, evolution, and limitations of Gender‐Based Analysis Plus (GBA+), which is the Government of Canada's primary framework for attending to diversity and inclusion in public policy. We argue that GBA+ is, in its current form, inadequate to guide ambitious and transformative policy in the post‐pandemic years given four interlocking issues: (1) a weak integration of intersectionality; (2) insufficient attention to the power structures and socio‐political context undergirding social relations and policymaking; (3) an instrumental understanding of policy; and (4) a misreading of identity. Drawing on feminist, intersectional and post‐structuralist methods, we adjust the GBA+ framework with the aim of addressing the conceptual shortcomings identified in our analysis. Ultimately, we demonstrate how a more explicit engagement with notions of intersectionality, power and policy's instrumental and productive aspects can enrich the ways we think about public policy as both a mechanism and a venue for transformative change.
Outpatient parotidectomy with or without the use of a post‐operative drain: A retrospective bi‐institutional study
Authors: Reerds Sam T. H. , Hey Shi Ying , van den Hoogen Frank J. A. , Takes Robert P. , Ganesh Vaishnevy , Marres Henri A. M. , Manickavasagam Jaiganesh , Honings Jimmie
Published: December 2022

Objective

Parotid surgery is historically performed as an inpatient procedure and suctions drains are predominantly used during surgery. Recent literature provides evidence that outpatient parotid surgery is safe and effective. Our study aims to describe the results of drainless outpatient parotidectomy and outpatient parotidectomy with drain placement and compare their outcomes.

Design

Retrospective cohort study.

Setting

Bi‐institutional retrospective cohort study.

Participants

Patients that underwent outpatient drain‐less parotidectomy and patients that underwent outpatient parotidectomy with post‐operative drain placement.

Main Outcome Measures

Complication rates, unplanned post‐operative visits, unplanned prolonged stay.

Results

Three hundred eighty patients underwent outpatient parotidectomy with drain placement and 31 patients underwent outpatient drainless parotidectomy in two different hospitals. The incidence of haematoma (drain: 3.1% vs. drainless: 0%, p = 1), infection (drain: 14.3% vs. drainless: 13.8%, p = 1) and salivary fistula (drain: 5.6% vs. drainless: 3.4, p = 1) were comparable between both groups. Seroma or sialocele was more frequently seen in the drain‐less group (27.6% vs. 6.2%, p < .001), but were all managed conservatively. Within 10 days after surgery, unplanned visits seemed more frequent in the drain group, although the difference was not statistically significant (14.9% vs. 3.4%, p = .16).

Conclusions

Outpatient parotid surgery with or without the use of a post‐operative drain is safe, practical and feasible. Same‐day discharge with and without drain placement yield comparable outcomes. However, the results need to be interpreted cautiously as this study was limited by a small cohort of parotidectomies without drain placement. Future studies should further compare both approaches.
CGM accuracy: Contrasting CE marking with the governmental controls of the USA (FDA) and Australia (TGA): A narrative review
Authors: Pemberton John S , Wilmot Emma G , Barnard‐Kelly Katharine , Leelarathna Lalantha , Oliver Nick , Randell Tabitha , Taplin Craig E , Choudhary Pratik , Adolfsson Peter
Published: December 2022

The National Institute for Clinical Excellence updated guidance for continuous glucose monitoring (CGM) in 2022, recommending that CGM be available to all people living with type 1 diabetes. Manufacturers can trade in the UK with Conformité Européenne (CE) marking without an initial national assessment. The regulatory process for CGM CE marking, in contrast to the Food and Drug Administration (FDA) and Australian Therapeutic Goods Administration (TGA) process, is described. Manufacturers operating in the UK provided clinical accuracy studies submitted for CE marking. Critical appraisal of the studies shows several CGM devices have CE marking for wide‐ranging indications beyond available data, unlike FDA and TGA approval. The FDA and TGA use tighter controls, requiring comprehensive product‐specific clinical data evaluation. In 2018, the FDA published the integrated CGM (iCGM) criteria permitting interoperability. Applying the iCGM criteria to clinical data provided by manufacturers trading in the UK identified several study protocols that minimized glucose variability, thereby improving CGM accuracy on all metrics. These results do not translate into real‐life performance. Furthermore, for many CGM devices available in the UK, accuracy reported in the hypoglycaemic range is below iCGM standards, or measurement is absent. We offer a framework to evaluate CGM accuracy studies critically. The review concludes that FDA‐ and TGA‐approved indications match the available clinical data, whereas CE marking indications can have discrepancies. The UK can bolster regulation with UK Conformity Assessed marking from January 2025. However, balanced regulation is needed to ensure innovation and timely technological access are not hindered.
The putative maintaining mechanism of gut bacterial ecosystem in giant pandas and its potential application in conservation
Authors: Cui Xinyuan , Zhang Qinrong , Zhang Qunde , Chen Hua , Liu Guoqi , Zhu Lifeng
Published: December 2022

Animals living in captivity and the wild show differences in the internal structure of their gut microbiomes. Here, we performed a meta‐analysis of the microbial data of about 494 fecal samples obtained from giant pandas (captive and wild giant pandas). Our results show that the modular structures and topological features of the captive giant panda gut microbiome differ from those of the wild populations. The co‐occurrence network of wild giant pandas also contained more nodes and edges, indicating a higher complexity and stability compared to that of captive giant pandas. Keystone species analysis revealed the differences between geographically different wild populations, indicating the potential effect of geography on the internal modular structure. When combining all the giant panda samples for module analysis, we found that the abundant taxa (e.g., belonged to Flavobacterium, Herbaspirillum, and Escherichia‐Shigella) usually acted as module hubs to stabilize the modular structure, while the rare taxa usually acted as connectors of different modules. We conclude that abundant and rare taxa play different roles in the gut bacterial ecosystem. The conservation of some key bacterial species is essential for promoting the development of the gut microbiome in pandas. The living environment of the giant pandas can influence the internal structure, topological features, and strength of interrelationships in the gut microbiome. This study provides new insights into the conservation and management of giant panda populations.
Ethical, legal, organizational and social issues related to the use of scalp cooling for the prevention of chemotherapy‐induced alopecia: A systematic review
Authors: Delgado Rodríguez Janet , Ramos‐García Vanesa , Infante‐Ventura Diego , Suarez‐Herrera José Carlos , Rueda‐Domínguez Antonio , Serrano‐Aguilar Pedro , del Mar Trujillo‐Martín María
Published: December 2022

Introduction

Scalp cooling (SC) aims to prevent chemotherapy‐induced alopecia. The goal of this systematic review is to tackle ethical, legal, organizational and social issues related to SC.

Methods

A critical appraisal of the literature was carried out using a systematic review design. MEDLINE, Embase and Web of Science databases were searched up until 2 June 2021. Studies addressing these aspects in English or Spanish were considered. Representatives of both patient associations and professional scientific societies related to the topic participated in the design of the protocol and the review of the findings.

Results

A total of 17 studies were included. Articles were critically appraised using the MMAT and SANRA. Findings were organized into four categories: (1) ethical aspects focused on equal access, gender equity and doctor–patient communication supported by Patient Decision Aids (PtDAs); (2) patient perspective and acceptability; (3) professional perspective and acceptability; (4) organizational aspects focused on accessibility and feasibility.

Conclusion

Cancer patients' expectations when using SC need to be adjusted to reduce the potential distress associated with hair loss. PtDAs could help patients clarify their values and preferences regarding SC. Equal access to technology should be guaranteed.

Patient or Public Contribution

In this systematic review, the representatives of the patient associations (Ms. María Luz Amador Muñoz of the Spanish Association Against Cancer [AECC] and Ms. Catiana Martinez Cánovas of the Spanish Breast Cancer Federation [FECMA]) participated in the review of the study protocol, as well as in the results, discussion and conclusions, making their contributions. In the type of design of these studies (systematic reviews), it is not usual to have the direct participation of patients, but in this one, we have done so, as it is a systematic review that is part of a report of the Spanish Network of Health Technology Assessment Agencies (ETS).
Setting an exam as an information design problem
Authors: Shimoji Makoto
Published: December 2022

We take a teacher's exam‐setting task as an information design problem. Specifically, the teacher chooses a conditional distribution of grades given students' types. After observing their exam results, each student updates her belief regarding her type via Bayes' rule and chooses an action. Students' reactions to the same exam result could be different, depending on their heterogeneous prior beliefs. The teacher's objective is to persuade students to take a certain action (e.g., applying to universities), which some may not choose without an exam. The teacher adopts different grade distributions, depending on the teacher's and the students' heterogeneous prior beliefs.