bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental and computational evaluation of knee implant wear and creep under in vivo and ISO boundary conditions
Authors: Dreyer Michael J. , Hosseini Nasab Seyyed Hamed , Favre Philippe , Amstad Fabian , Crockett Rowena , Taylor William R. , Weisse Bernhard
Published: May 2023

Experimental knee implant wear testing according to ISO 14243 is a standard procedure, but it inherently possesses limitations for preclinical evaluations due to extended testing periods and costly infrastructure. In an effort to overcome these limitations, we hereby develop and experimentally validate a finite element (FE) based algorithm, including a novel cross-shear and contact pressure dependent wear and creep model, and apply it towards understanding the sensitivity of wear outcomes to the applied boundary conditions.

Specifically, we investigated the application of in vivo data for level walking from the publicly available “Stan” dataset, which contains single representative tibiofemoral loads and kinematics derived from in vivo measurements of six subjects, and compared wear outcomes against those obtained using the ISO standard boundary conditions. To provide validation of the numerical models, this comparison was reproduced experimentally on a six-station knee wear simulator over 5 million cycles, testing the same implant Stan’s data was obtained from.

Experimental implementation of Stan’s boundary conditions in displacement control resulted in approximately three times higher wear rates (4.4 vs. 1.6 mm3per million cycles) and a more anterior wear pattern compared to the ISO standard in force control. While a force-controlled ISO FE model was unable to reproduce the bench test kinematics, and thus wear rate, displacement-controlled FE models accurately predicted the laboratory wear tests for both ISO and Stan boundary conditions. The credibility of the in silico wear and creep model was further established per the ASME V&V-40 standard. The model is thus suitable for supporting future patient specific models and development of novel implant designs.
Fulgor: A fast and compactk-mer index for large-scale matching and color queries
Authors: Fan Jason , Singh Noor Pratap , Khan Jamshed , Pibiri Giulio Ermanno , Patro Rob
Published: May 2023

The problem of sequence identification or matching — determining the subset of references from a given collection that are likely to contain a query nucleotide sequence — is relevant for many important tasks in Computational Biology, such as metagenomics and pan-genome analysis. Due to the complex nature of such analyses and the large scale of the reference collections a resource-efficient solution to this problem is of utmost importance. The reference collection should therefore be pre-processed into anindexfor fast queries. This poses the threefold challenge of designing an index that is efficient to query, has light memory usage, and scales well to large collections.

To solve this problem, we describe how recent advancements in associative, order-preserving,k-mer dictionaries can be combined with a compressed inverted index to implement a fast and compactcolored de Bruijngraph data structure. This index takes full advantage of the fact that unitigs in the colored de Bruijn graph aremonochromatic(allk-mers in a unitig have the same set of references of origin, or “color”), leveraging theorder-preservingproperty of its dictionary. In fact,k-mers are kept in unitig order by the dictionary, thereby allowing for the encoding of the map fromk-mers to their inverted lists in as little as 1 +o(1) bits per unitig. Hence, one inverted list per unitig is stored in the index with almost no space/time overhead. By combining this property with simple but effective compression methods for inverted lists, the index achieves very small space.

We implement these methods in a tool calledFulgor. Compared toThemisto, the prior state of the art,Fulgorindexes a heterogeneous collection of 30,691 bacterial genomes in 3.8× less space, a collection of 150,000Salmonella entericagenomes in approximately 2 × less space, is at least twice as fast for color queries, and is 2 − 6× faster to construct.

2012 ACM Subject Classification

Applied computing → Bioinformatics
Population genomics reveals extensive inbreeding and purging of mutational load in wild Amur tigers
Authors: Lan Tianming , Li Haimeng , Zhang Le , Shi Minhui , Liu Boyang , Cui Liangyu , Dussex Nicolas , Wang Qing , Ma Yue , Liu Dan , Kong Weiyao , Wang Jiangang , Lu Haorong , Zhang Shaofang , Yu Jieyao , Wang Xinyu , Wu Yuxin , Niu Xiaotong , Fan Jiale , Zhao Yue , Dalén Love , Jiang Guangshun , Liu Huan , Xu Yanchun
Published: May 2023

The inbreeding is a big threat for the persistence of genetic diversity in small and isolated populations of endangered species. The homozygous genome could exacerbate inbreeding depression by introducing homozygous deleterious alleles in the population. However, purging of inbreeding loads as they become homozygotes in small populations could alleviate the depression. The Amur tiger (Panthera tigris altaica) is typically exists in small population living in forests in Northeast Asia and is among the most endangered animals on the planet with great symbolic significance of conservation. By comparing with captive individuals, we revealed substantially higher and more extensive inbreeding in the wild Amur tiger population (FROH=0.51) than in captive Amur tigers (FROH=0.26). We further found much less mutational loads in wild populations when compared with captive Amur tigers. However, the frequency of loss of function and deleterious nonsynonymous mutations inside ROH regions are much lower than that in non-ROH regions in both wild and captive Amur tigers, indicating the purging may had occurred in both populations but much effective in the wild population. In addition, we found the average frequency of deleterious alleles was much lower than that of neutral alleles in the wild population, indicating that the purifying selection contributed to the purging of mutational loads in the wild Amur tigers. These findings provide valuable genome-wide evidence to support the making of future conservation plans of wild Amur tigers.
DIURETIC AND ANTI-HYPERTENSIVE ACTIVITY OFCLERODENDRUM CHINENSE(OSBECK) MABB. AQUEOUS EXTRACT IN 8% SALT DIET INDUCED HYPERTENSIVE RATS
Authors: Odimegwu Joy I. , Okanlawon Tolulope F. , Olatunji Oluwakayode Ezekiel , Ishola Ismail
Published: May 2023

Diuresis refers to increase in the rate of urine flow and sodium excretion from the system via the urine. It is a necessary excretory process that may prove difficult for some disease systems e.g. enlarged prostates. Hypertension occurs as a result of systolic blood pressure higher than 140 mmHg or a diastolic blood pressure higher than 90 mmHg. It is one of the most common chronic diseases affecting more a billion people worldwide. A high dietary sodium intake is one of the factors associated with the development of hypertension.Clerodendrum chinensisis used by local communities in West Africa for its diuretic and anti-hypertensive properties. We analyse the phytochemical properties of the mixed leaf, root and stem aqueous extract of the plant and investigate its anti-hypertensive and diuretic activity in Sodium chloride diet induced hypertensive rats. The anti-hypertensive effect of extract at different concentrations (100, 200 and 300 mg/kg) was studied and compared with known drug compound; Furosemide. Treated animal urine was analyzed for urinary excretion and diuretic action. The anti-hypertensive effect was statistically significant when compared with the control p < 0.001. The extract at 100mg/kg demonstrated the best systolic and diastolic blood pressure lowering potential as compared to other concentrations. The diuretic action of the plant extract at the lowest dose (100 mg/kg) was high and quantitatively similar to the standard drug. The combined powdered leaf, stem and roots aqueous extract ofC. chinensepossesses anti-hypertensive and diuretic potential in salt loaded hypertensive rats.
Sugar distributions on gangliosides guide the formation and stability of amyloid-β oligomers
Authors: Saha Jhinuk , Ford Brea J. , Boyd Sydney , Rangachari Vijayaraghavan
Published: May 2023

Aggregation of Aβ peptides has been known as a key contributor to the etiology of Alzheimer’s disease. Being intrinsically disordered, the monomeric Aβ is susceptible to conformational excursions, especially in the presence of key interacting partners such as membrane lipids, to adopt specific aggregation pathways. Furthermore, key components such as gangliosides in membranes and lipid rafts are known to play important roles in the adoption of pathways and the generation of discrete neurotoxic oligomers. Yet, what roles the carbohydrates on gangliosides play in this process remains unknown. Here, using GM1, GM3, and GD3 ganglioside micelles as models, we show that the sugar distributions and cationic amino acids within Aβ N-terminal region modulate oligomerization of Aβ temporally, and dictate the stability and maturation of oligomers.
Modulation of somatosensory signal transmission in the primate cuneate nucleus during voluntary hand movement
Authors: Kubota Shinji , Sasaki Chika , Kikuta Satomi , Ito Sho , Gomi Hiroaki , Oya Tomomichi , Seki Kazuhiko
Published: May 2023

Successful extraction of tactile and kinematic information is crucial for appropriate motor actions in daily life. To achieve this objective, sensory signals should be effectively regulated during motor actions. This regulation is understood both empirically and conceptually, but it is not well known where and how it is implemented in the central nervous system. Here, we show that, during voluntary movement, sensory signals are already attenuated in the primate cuneate nucleus, an early processing site in the ascending lemniscus pathway. The degree of suppression was comparable with the one reported in the cortex, suggesting that psychological attenuation of somatosensation could be ascribed to the cuneate. The results also revealed that this sensory attenuation was of descending origin, suggesting that cortical sensory prediction signals could regulate cuneate sensory transmission for extracting meaningful, and attenuate unnecessary, signals for movement regulation. This recurrent sensory modulation mechanism between cortical and subcortical areas may generalize to other sensory modalities and cognitive processes.
Investigating the Relationship Between Radiotherapy Dose on the neurogenic niches and Overall Survival in NSCLC Brain Metastases
Authors: Cialdella Fia , Bruil Danique E. , van der Boog A.T.J. , Nagtegaal Steven H.J , de Vos F.Y.F. , Verhoeff J.J.C. , David Szabolcs
Published: May 2023

Background

Non-small cell lung cancer (NSCLC), the most common type of lung cancer, often leads to brain metastases (BMs) with a poor prognosis. Radiotherapy is the main treatment for BMs, which despite decades of development, still results in radiation of healthy tissue. Neural stem cells (NSCs), crucial for the establishment and preservation of the nervous system, are sensitive to radiation, therefore radiation damage to NSCs may affect overall survival (OS). NSCs are primarily located in the subventricular zone (SVZ) and the subgranular zone (SGZ) within the hippocampus (HPC). Our study aims to evaluate the impact of radiotherapy dose on NSCs on OS in patients with BMs from NSCLC.

Methods

We have retrospectively included 138 NSCLC patients with BMs, irradiated at a single academic institute. NSC regions were delineated on the non-enhanced T1 MR images with CAT12 and SPM. The association between regional mean doses in the SVZ and HPC and OS was examined using a Cox regression model. Additionally, survival differences between lesion contact and no direct contact with SVZ and HPC were investigated with Kaplan-Meier (KM) analysis.

Findings

Multivariable Cox regression of dose on the SVZ and HPC showed a significant negative correlation, with a hazard ratio (HR) of 1.366 (p = 0.041 [95% (CI) 1.013– 1.842]) and 1.194 (p = 0.037 [95% CI 1.010 – 1.411]), respectively. KM analysis did not find a relationship between lesion contact with NSC-regions and OS.

Interpretation

Radiotherapy dose on the neurogenic niches is correlated with poorer OS and we found no association between direct lesion contact to NSC-regions and OS. We recommend further investigation into the impact of radiation on OS and neurocognitive function in a prospective study design in order to develop treatment approaches that minimize the potential harm to NSC’s while maximizing effectiveness.

Funding

Received no funds, grants, or support.
Study protocol for a Critical Realist pilot cluster-randomised controlled trial of a whole-school-based mindfulness intervention (SBMI) promoting child and adolescent mental wellbeing in Rwanda and Ethiopia
Authors: Abbott Pamela , D’Ambruoso Lucia , Yared Mahlet , McNamee Paul , Hailu Tsion , Nzabalirwa Wenceslas
Published: May 2023

Abstract

Background

This research uses a critical realist approach to understand how and why school-based mindfulness interventions designed to promote child and adolescent mental wellbeing work or do not. Poor mental wellbeing is the leading cause of illness among children and adolescents in sub-Saharan Africa, with an estimated prevalence of 1 in 7. There is evidence that school-based mindfulness interventions promote child and adolescent wellbeing. Still, few interventions have been trialled in SSA, and none have examined how and why mindfulness interventions work.

Methods

Using a Critical Realist pilot cluster-randomised controlled trial; we will evaluate a school-based mindfulness intervention compared to the regular curriculum over one school year. Incorporating mindfulness into the primary school curriculum will provide proactive reach to all CA. The intervention will be codesigned by teacher educators, schoolteachers, policy actors and community members, including CAs. In each country, three schools will be selected and randomised as pilot, intervention, or control/waitlist. The mindfulness intervention will be integrated into the school curriculum and taught to all children attending the schools by classroom teachers trained to deliver it. Quantitative research will be used to measure the outcome of the intervention, and qualitative research to answer how and why questions. The primary outcome is improved mental wellbeing of pupils measured by the Acholi Psychological Assessment Instrument. Secondary outcomes will include subjective quality of life, school 'climate', school performance, and satisfaction with school. Pupils, teachers and main carers in intervention and control/waitlist schools will fill in questionnaires before and after the intervention and process evaluation will be carried out in intervention schools. The cost-effectiveness of the mindfulness intervention will be assessed.

Discussion

The evaluation will provide new interdisciplinary knowledge, and methods, to understand and sustainable impacts on CA mental wellbeing in these settings. Independent research and intervention teams will run the trial.

Registration of Project: Research Registry 8799, Mar 31 2023
A digital health intervention to support patients with chronic pain during prescription opioid tapering: a pilot randomised controlled trial
Authors: Gholamrezaei Ali , Magee Michael R , McNeilage Amy G , Dwyer Leah , Sim Alison , Ferreira Manuela L , Darnall Beth D , Brake Timothy , Aggarwal Arun , Craigie Meredith , Hollington Irina , Glare Paul , Ashton-James Claire E
Published: May 2023

Introduction:Recent changes in opioid prescribing guidelines have led to an increasing number of patients with chronic pain being recommended to taper. However, opioid tapering can be challenging, and many patients require support.

Objectives:We evaluated the feasibility, acceptability, and potential efficacy of a co-designed psycho-educational video and SMS text messaging intervention to support patients with chronic pain during prescription opioid tapering.

Methods:A pilot randomised controlled trial was conducted. In addition to their usual care, participants in the intervention group received a psycho-educational video and 28 days of text messages (two SMS/day). The control group received usual care. The feasibility, acceptability, and potential efficacy of the intervention were evaluated. The primary outcome was opioid tapering self-efficacy. Secondary outcomes were pain intensity and interference, anxiety and depression symptom severity, pain catastrophising, and pain self-efficacy.

Results:Of 28 randomised participants, 26 completed the study (13 in each group). Text message delivery was 99.2% successful. Most participants rated the messages as useful, supportive, encouraging, and engaging, 78.5% would recommend the intervention to others, and 64% desired a longer intervention period. Tapering self-efficacy (Cohen’sd= 0.74) and pain self-efficacy (d= 0.41) were higher and pain intensity (d= 0.65) and affective interference (d= 0.45) lower in the intervention group at week 4.

Conclusions:It is feasible, acceptable, and potentially efficacious to support patients with chronic pain during prescription opioid tapering with a psycho-educational video and SMS text messaging intervention. A definitive trial has been initiated to test a 12-week intervention.
Large-scale cerebrospinal fluid proteomic analysis in Alzheimer’s disease patients reveals five molecular subtypes with distinct genetic risk profiles
Authors: Tijms Betty M , Vromen Ellen M , Mjaavatten Olav , Holstege Henne , Reus Lianne M , van der Lee Sven , Wesenhagen Kirsten EJ , Lorenzini Luigi , Vermunt Lisa , Venkatraghavan Vikram , Tesi Niccoló , Tomassen Jori , den Braber Anouk , Goossens Julie , Vanmechelen Eugeen , Barkhof Frederik , Pijnenburg Yolande AL , van der Flier Wiesje M , Teunissen Charlotte E , Berven Frode , Visser Pieter Jelle
Published: May 2023

Alzheimer’s disease (AD) is heterogenous on the molecular level. Understanding this heterogeneity is critical for AD drug development. We aimed to define AD molecular subtypes by mass spectrometry proteomics in cerebrospinal fluid (CSF). Of the 3863 proteins detected in CSF, 1058 proteins had different levels in individuals with AD (n=419) compared with controls (n=187). Cluster analyses of AD individuals on these 1058 proteins revealed five subtypes: subtype 1 was characterized by neuronal hyperplasticity; subtype 2 by innate immune activation; subtype 3 by RNA dysregulation; subtype 4 by choroid plexus dysfunction; and subtype 5 by blood-brain barrier dysfunction. Distinct genetic profiles were associated with subtypes, e.g., subtype 1 was enriched withTREM2 R47H. Subtypes also differed in brain atrophy and clinical outcomes. For example, survival was shorter in subtype 3 compared to subtype 1 (5.6 versus 8.9 years). These novel insights into AD molecular heterogeneity highlight the need for personalized medicine.
Prenatal Lead Exposure is Negatively Associated with the Gut Microbiome in Childhood
Authors: Eggers Shoshannah , Midya Vishal , Bixby Moira , Gennings Chris , Torres-Olascoaga Libni A , Walker Ryan W. , Wright Robert O. , Arora Manish , Téllez-Rojo Martha María
Published: May 2023

Background

Metal exposures are associated with gut microbiome (GM) composition and function, and exposures early in development may be particularly important. Considering the role of the GM in association with many adverse health outcomes, understanding the relationship between prenatal metal exposures and the GM is critically important. However, there is sparse knowledge of the association between prenatal metal exposure and GM later in childhood.

Objectives

This analysis aims to identify associations between prenatal lead (Pb) exposure and GM composition and function in children 9-11 years old.

Methods

Data come from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort based in Mexico City, Mexico. Prenatal metal concentrations were measured in maternal whole blood drawn during the second and third trimesters of pregnancy. Stool samples collected at 9-11 years old underwent metagenomic sequencing to assess the GM. This analysis uses multiple statistical modeling approaches, including linear regression, permutational analysis of variance, weighted quantile sum regression (WQS), and individual taxa regressions, to estimate the association between maternal blood Pb during pregnancy and multiple aspects of the child GM at 9-11 years old, adjusting for relevant confounders.

Results

Of the 123 child participants in this pilot data analysis, 74 were male and 49 were female. Mean prenatal maternal blood Pb was 33.6(SE=2.1) ug/L and 34.9(SE=2.1) ug/L at second and third trimesters, respectively. Analysis suggests a consistent negative relationship between prenatal maternal blood Pb and the GM at age 9-11, including measures of alpha and beta diversity, microbiome mixture analysis, and individual taxa. The WQS analysis showed a negative association between prenatal Pb exposure and the gut microbiome, for both second and third trimester exposures (2Tβ=-0.17,95%CI=[-0.46,0.11]; 3Tβ=-0.17,95%CI=[-0.44,0.10]). Ruminococcus gnavus, Bifidobacterium longum, Alistipes indistinctus, Bacteroides caccae, and Bifidobacterium bifidum all had weights above the importance threshold from 80% or more of the WQS repeated holdouts in association with both second and third trimester Pb exposure.

Discussion

Pilot data analysis suggests a negative association between prenatal Pb exposure and the gut microbiome later in childhood; however, additional investigation is needed.
Downregulation of CYP7B1 caused by lipotoxicity associates with the progression of non-alcoholic steatohepatitis
Authors: Watanabe Yuichi , Kinoshita Kyohei , Dumrongkulchart Napatsorn , Sasaki Takashi , Shimizu Makoto , Yamauchi Yoshio , Sato Ryuichiro
Published: May 2023

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with an incidence of >25% of the adult population. NAFLD ranges from benign simple steatosis to non-alcoholic steatohepatitis (NASH). However, its transition mechanisms underlying the pathogenesis remain to be clarified. The expression ofCyp7b1gene is downregulated in the liver of leptin-deficient mice and methionine and choline-deficient diet-fed mice based on previous microarray data. Thus, in this study, we investigated the effect of CYP7B1 restoration on the progression of NASH in mice fed MCD diet and its association with oxidative and lipid stresses. Our results suggest that restoration of CYP7B1 expression attenuates hepatitis and fibrosis and that lipid and oxidative stresses observed in the early stage of NASH suppressesCyp7b1transcription in hepatocytes.
A High-Throughput Sampling Method for Detection ofMeloidogyne enterolobiiand Other Root-Knot Nematodes in Sweetpotato Storage Roots
Authors: Culbreath Julianna , Wram Catherine , Khanal Churamani , Bechtel Tyler , Wadl Phillip A. , Mueller John , Rutter William B.
Published: May 2023

Meloidogyne enterolobiiis an aggressive root-knot nematode (RKN) species that has emerged as a significant pathogen of sweetpotato in the Southeastern United States.M. enterolobiiis spread primarily through the movement of infected ‘seed’ sweetpotatoes used for propagation. The RKN resistance in commercially grown sweetpotato cultivars has proven ineffective against this nematode. Detecting RKN in sweetpotato by eye is unreliable, and further distinguishingM. enterolobiifrom other RKN species that infect sweetpotato is labor intensive; relying on molecular tests conducted on individual nematodes dissected out of host roots by trained technicians. Here, we have developed a high-throughput survey method to collect skin samples and extract total DNA from batches of sweetpotato storage roots. Combining this method with species-specific PCR assays allowed for quick and sensitive detection ofM. enterolobiiand other RKN species infecting sweetpotatoes. We tested this method using batches of infected storage roots at varying levels ofM. enterolobiiinfection. We also inoculated skin samples with varying numbers of individualM. enterolobiieggs to determine the method’s detection threshold and used this method to conduct surveys for RKN on fresh market sweetpotatoes. Our results show that this method can consistently and reliably detectM. enterolobiiin sweetpotato batches at levels as low as 2 eggs per 10 mL skin sample. This method will be a useful tool to help screen for the presence ofM. enterolobiiin ‘seed’ sweetpotatoes before they are replanted, thereby helping to slow the spread of this nematode toM. enterolobii-free sweetpotato growing operations.
Effect of quercetin and kaempferol isolated from theGinkgo bilobaL. suspension culture extract on lipofuscin accumulation
Authors: Milentyeva Irina Sergeyevna , Fedorova Anastasia Mikhailovna , Vesnina Anna Dmitrievna , Prosekov Alexander Yurievich , Asyakina Ludmila Konstantinovna , Neverova Olga Alexandrovna
Published: May 2023

Lipofuscin, known as an age pigment, is an autofluorescent lipopigment formed by lipids, metals, and misfolded proteins that accumulates in nerve cells, heart muscle cells, and skin. Individual bioactive compounds obtained from medicinal plant extracts reduce the level of lipofuscin inC. elegansnematodes inin vivoexperiments. We aimed to study the effect of quercetin and kaempferol isolated from thein vitrosuspension culture extracts ofGinkgo bilobaL. on the accumulation of lipofuscin. According to the results, 200 μM concentrations of these bioactive compounds showed the maximum decrease in lipofuscin levels inC. elegansN2 Bristol during their 15-day cultivation, compared to the control. Thus, our study showed that quercetin and kaempferol are able to reduce this age pigment inin vivoexperiments.
PTCH1mutant human cerebellar organoids are associated with altered neural development and early pathways of medulloblastoma oncogenesis
Authors: van Essen Max J. , Riepsaame Joey , Cowley Sally A. , Jacob John , Becker Esther B. E.
Published: May 2023

Patched 1 (PTCH1) is the primary receptor for Sonic Hedgehog (SHH) ligand and negatively regulates SHH signalling, an essential pathway in human embryogenesis. Loss-of-function mutations inPTCH1are associated with altered neuronal development and the malignant brain tumour medulloblastoma (MB). As a result of differences between murine and human development, molecular and cellular perturbations that arise from humanPTCH1mutations remain poorly understood. Here, we employ cerebellar organoids differentiated from human induced pluripotent stem cells (iPSC) combined with CRISPR/Cas9 gene editing to investigate the earliest molecular and cellular consequences ofPTCH1mutations on human cerebellar development. Our findings support the occurrence of developmental mechanisms in cerebellar organoids that mirrorin vivoprocesses of regionalisation and SHH signalling, and offer new insight into early pathophysiological events of MB tumorigenesis.

Higlights

Differentiation of human iPSC into cerebellar organoids

Homozygous LOF ofPTCH1prevents cerebellar organoid differentiation

PTCH1+/-cerebellar organoids display tissue-specific effects of SHH signalling

Early altered gene expression relevant for MB inPTCH1+/-cerebellar organoids
Syndecan-1 as specific cerebrospinal fluid biomarker of multiple sclerosis
Authors: Hinsinger Geoffrey , Du Trieu de Terdonck Lucile , Urbach Serge , Salvetat Nicolas , Rival Manon , Galoppin Manon , Ripoll Chantal , Cezar Renaud , Laurent-Chabalier Sabine , Demattei Christophe , Agherbi Hanane , Castelnovo Giovanni , Lehmann Sylvain , Rigau Valérie , Marin Philippe , Thouvenot Eric
Published: May 2023

Multiple sclerosis (MS) is an inflammatory demyelinating disease often characterized by remission and relapse periods occurring at irregular intervals after an initial attack (clinically isolated syndrome) and followed by a gradual progression of disability. Clinical symptoms, magnetic resonance imaging and abnormalities in cerebrospinal fluid (CSF) immunoglobulin profile allow diagnosis with a good sensitivity. However, current biomarkers lack specificity or have poor individual prognostic value. To identify novel candidate biomarkers of MS, we analysed 1) the CSF proteome from symptomatic controls and patients with clinically isolated syndrome or remitting-relapsing multiple sclerosis (n=40), and 2) changes in oligodendrocyte secretome upon proinflammatory or pro-apoptotic treatment. Proteins exhibiting differences in abundance in both studies were combined with previously described MS biomarkers to build a list of 87 proteins that were quantified by parallel reaction monitoring (PRM) in CSF samples from a new cohort comprising symptomatic controls and MS patients at different disease stages (n=60). The eleven proteins that passed this qualification step were subjected to a new PRM assay from a larger cohort (n=158) comprising patients with MS at different disease stages or with other inflammatory or non-inflammatory neurological disorders. Collectively, these studies identified a biomarker signature of MS that might improve MS diagnosis and prognosis. These include the oligodendrocyte precursor cell proteoglycan Syndecan-1, which was more efficient than previously described biomarkers to discriminate MS from other inflammatory and non-inflammatory neurological disorders.
Preference Shifts During Multi-Attribute Value-Based Decisions
Authors: Nakahashi Ayuno , Cisek Paul
Published: May 2023

When choosing between options with multiple attributes, do we decide by integrating all of the attributes into a unified measure for comparison, or does the comparison occur at the level of each attribute, involving independent competitive processes that can dynamically influence each other? What happens when independent sensory features all carry information about the same decision factor, such as reward value? To investigate these questions, we asked human participants to perform a two-alternative forced choice task in which the reward value of a target was indicated by two independent visual attributes – its brightness (“bottom-up” feature) and its orientation (“top-down” feature). If decisions always occur after integration of both features, there should be no difference in the reaction time (RT) distribution regardless of the attribute combinations that drove the choice. Counter to that prediction, almost two-thirds of the participants exhibited RT differences that depended on the attribute combinations of given targets. The RT was shortest when both attributes were congruent or when the choice was based on the bottom-up feature, and longer when the attributes were in conflict (favoring opposite options), especially when choosing the option favored by the top-down feature. We also observed mid-reach changes-of-mind in a subset of conflict trials, mostly changing from the bottom-up to the top-down-favored target. These data suggest that multi-attribute value-based decisions are better explained by a distributed competition among different features than by a competition based on a single, integrated estimate of choice value.

New & Noteworthy

This study showed that during value-based decisions, humans do not always take all information about reward value into account to make their choice, but instead can “jump the gun” using partial information. In particular, when different sources of information were in conflict, early decisions were mostly based on fast bottom-up information, and sometimes followed by corrective changes-of-mind based on slower top-down information. Our results suggest that parallel decision processes occur among different information sources, as opposed to between a single integrated “common currency”.
Inhibition of Carbonic Anhydrase Using Aspirin is a Novel Method to Block Schistosomiasis Infection of the Parasitic Trematode,Schistosoma mansoni,in the intermediate snail host,Biomphalaria glabrata
Authors: Parn Simone , Lewis Gabriela , Knight Matty
Published: May 2023

Schistosomiasis is a major public health concern worldwide. Although praziquantel is currently available as the only treatment option for schistosomiasis, the absence of reliable diagnostic and prognostic tools highlights the need for the identification and characterization of new drug targets. Recently, we identified theB. glabratahomolog (accession number XP_013075832.1) of human CAXIV, showing 37% amino acid sequence identity, from a BLAST search in NCBI (National Center for Biotechnology Information). Carbonic Anhydrases (CAs) are metalloenzymes that catalyze the reversible hydration/dehydration of CO2/HCO3. These enzymes are associated with many physiological processes, and their role in tumorigenesis has been widely implicated. CAs create an acidic extracellular environment that facilitates the survival, metastasis, and growth of cancer cells. In this study, we investigated the role of CA inhibition inB. glabratasnails exposed toS. mansonimiracidia. We analyzed the expression of theB. glabrataCA encoding transcript in juvenile susceptible and resistant snails, with and without exposure toS. mansoni. Our results showed that the expression of the CA mRNA encoding transcript was upregulated during early and prolonged infection in susceptible snails (BBO2), but not in the resistant BS-90 stock. Notably, sodium salicylate, a form of aspirin, inhibited the expression of CA, post-exposure, to the parasite. Increasing research between parasites and cancer has shown that schistosomes and cancer cells share similarities in their capacity to proliferate, survive, and evade host immune mechanisms. Here, we show that this model system is a potential new avenue for understanding the role of CA in the metastasis and proliferation of cancer cells. Further studies are needed to explore the potential of CA as a biomarker for infection in other schistosomiasis-causing parasites, includingS. japonicumandS. haematobium.
Generalized fear following acute stress is caused by change in co-transmitter identity of serotonergic neurons
Authors: Li Hui-quan , Jiang Wuji , Ling Lily , Gupta Vaidehi , Chen Cong , Pratelli Marta , Godavarthi Swetha K. , Spitzer Nicholas C.
Published: May 2023

Overgeneralization of fear to harmless situations is a core feature of anxiety disorders resulting from acute stress, yet the mechanisms by which fear becomes generalized are poorly understood. Here we show that generalized fear in mice in response to footshock results from a transmitter switch from glutamate to GABA in serotonergic neurons of the lateral wings of the dorsal raphe. We observe a similar change in transmitter identity in the postmortem brains of PTSD patients. Overriding the transmitter switch in mice using viral tools prevents the acquisition of generalized fear. Corticosterone release and activation of glucocorticoid receptors trigger the switch, and prompt antidepressant treatment blocks the co-transmitter switch and generalized fear. Our results provide new understanding of the plasticity involved in fear generalization.

One sentence summary

Acute stress produces generalized fear by causing serotonergic neurons to switch their co-transmitter from glutamate to GABA
The Heterogeneous Effects of Lockdown Policies on Air Pollution∗
Authors: Briole Simon , Colette Augustin , Lavaine Emmanuelle
Published: May 2023

While a sharp decline in air pollution has been documented during early Covid-19 lockdown periods, the stability and homogeneity of this effect are still under debate. Building on pollution data with a very high level of resolution, this paper estimates the impact of lockdown policies onPM2.5exposure in France over the whole year 2020. Our analyses highlight a surprising and undocumented increase in exposure to particulate pollution during lockdown periods. This result is observed during both lockdown periods, in early spring and late fall, and is robust to several identification strategies and model specifications. Combining administrative datasets with machine learning techniques, this paper also highlights strong spatial heterogeneity in lockdown effects, especially according to long-term pollution exposure.

JEL Codes:C23, I18, Q53
Mouse frontal cortex nonlinearly encodes sensory, choice and outcome signals
Authors: Wool Lauren E. , Lak Armin , Carandini Matteo , Harris Kenneth D.
Published: May 2023

Frontal area MOs (secondary motor area) is a key brain structure in rodents for making decisions based on sensory evidence and on reward value. In behavioral tasks, its neurons can encode sensory stimuli, upcoming choices, expected rewards, ongoing actions, and recent outcomes. However, the information encoded, and the nature of the resulting code, may depend on the task being performed. We recorded MOs population activity using two-photon calcium imaging, in a task requiring mice to integrate sensory evidence with reward value. Mice turned a wheel to report the location of a visual stimulus following a delay period, to receive a reward whose size varied over trial blocks. MOs neurons encoded multiple task variables, but not all of those seen in other tasks. In the delay period, the MOs population strongly encoded the stimulus side but did not significantly encode the reward-size block. A correlation of MOs activity with upcoming choice could be explained by a common effect of stimulus on those two correlates. After the wheel turn and the feedback, the MOs population encoded choice side and choice outcome jointly and nonlinearly according to an exclusive-or (XOR) operation. This nonlinear operation would allow a downstream linear decoder to infer the correct choice side (i.e., the side that would have been rewarded) even on zero contrast trials, when there had been no visible stimulus. These results indicate that MOs neurons flexibly encode some but not all variables that determine behavior, depending on task. Moreover, they reveal that MOs activity can reflect a nonlinear combination of these behavioral variables, allowing simple linear inference of task events that would not have been directly observable.
Deficient synaptic neurotransmission results in a persistent sleep-like cortical activity across vigilance states in mice
Authors: Guillaumin Mathilde C. C. , Harding Christian D. , Krone Lukas B. , Yamagata Tomoko , Kahn Martin C. , Blanco-Duque Cristina , Banks Gareth T. , Nolan Patrick M. , Peirson Stuart N. , Vyazovskiy Vladyslav V.
Published: May 2023

Growing evidence suggests that brain activity during sleep, as well as sleep regulation, are tightly linked with synaptic function and network excitability at the local and global levels. We previously reported that a mutation in synaptobrevin 2 (Vamp2) in restless (rlss) mice results in a marked increase of wakefulness and suppression of sleep, in particular REM sleep (REMS) as well as increased consolidation of sleep and wakefulness. In the current study, using finer-scalein vivoelectrophysiology recordings, we report that spontaneous cortical activity inrlssmice during NREM sleep (NREMS) is characterised by an occurrence of abnormally prolonged periods of complete neuronal silence (OFF-periods), often lasting several seconds, similar to the burst suppression pattern typically seen under deep anaesthesia. Increased incidence of prolonged network OFF-periods was not specific to NREMS, but also present in REMS and wake inrlssmice. Slow-wave activity (SWA) was generally increased inrlssmice, while higher frequencies including theta-frequency activity were decreased, further resulting in diminished differences between vigilance states. The relative increase in SWA after sleep deprivation was attenuated inrlssmice, suggesting either thatrlssmice experience persistently elevated sleep pressure, or, alternatively, that the intrusion of sleep-like patterns of activity into awake state diminishes the accumulation of sleep drive. We propose that deficit in global synaptic neurotransmitter release leads to ‘state inertia’, reflected in an abnormal propensity of brain networks to enter and remain in a persistent ‘default state’ resembling coma or deep anaesthesia.
Developing an outcome measure for an adult intellectual disabilities intensive support team – a practice paper
Authors: Lines Jason , Krishnadas Kiran
Published: May 2023

Purpose

This paper aims to outline the initial pilot use of the client complexity matrix (CCM), an outcome measure developed for an NHS Adult Intellectual Disabilities Intensive Support Team (IST) in the West Midlands of England.

Design/methodology/approach

A mixed method approach was used to report the results and evaluate the use of the CCM within this IST. The CCM was trialled for six months between January 2022 and June 2022. CCM scores pre and post IST intervention were analysed via t-test, and qualitative feedback from clinicians is detailed.

Findings

Analysis suggests the CCM captures service success showing a significant decrease in complexity and risk post-intervention. Qualitative comments from clinicians were generally positive; however, there were requested changes regarding specific presentations, use of labels/language and for a digital version.

Research limitations/implications

The tool is not co-constructed with the client. Because of this IST’s caseload, the sample size was small. Only one clinician was asked to complete the CCM pre and post intervention. Future use of the measure will encourage two clinicians to complete the measure to evidence its inter-rater reliability. Each client’s specific presentation was not explicitly analysed here.

Practical implications

The CCM will be updated using the feedback from clinicians and from the peer review process. Research that examines the generalisability of this measure to other IST services would be beneficial.

Originality/value

The CCM appears to fill a gap in outcome measurements for this IST service which looks at breadth and depth of client complexity and risk.
On the zero state-response of the ℑ-order R-C circuit within the local fractional calculus
Authors: Wang Kang-Jia , Liu Jing-Hua
Published: May 2023

Purpose

As a powerful mathematical analysis tool, the local fractional calculus has attracted wide attention in the field of fractal circuits. The purpose of this paper is to derive a new

ℑ-order non-differentiable (ND) R-C zero state-response circuit (ZSRC) by using the local fractional derivative on the Cantor set for the first time.

Design/methodology/approach

A new

ℑ-order ND R-C ZSRC within the local fractional derivative on the Cantor set is derived for the first time in this work. By defining the ND lumped elements via the local fractional derivative, the

ℑ-order Kirchhoff voltage laws equation is established, and the corresponding solutions in the form of the Mittag-Leffler decay defined on the Cantor sets are derived by applying the local fractional Laplace transform and inverse local fractional Laplace transform.

Findings

The characteristics of the

ℑ-order R-C ZSRC on the Cantor sets are analyzed and presented through the 2-D curves. It is found that the

ℑ-order R-C ZSRC becomes the classic one when

ℑ = 1. The comparative results between the

ℑ-order R-C ZSRC and the classic one show that the proposed method is correct and effective and is expected to shed light on the theory study of the fractal electrical systems.

Originality/value

To the best of the authors’ knowledge, this paper, for the first time ever, proposes the

ℑ-order ND R-C ZSRC within the local fractional derivative on the Cantor sets. The results of this paper are expected to give some new enlightenment to the development of the fractal circuits.
Addressing data quality in Airbnb research
Authors: Prentice Catherine , Pawlicz Adam
Published: May 2023

Purpose

This paper aims to examine the primary supply data sources that have been used for research into the sharing economy, and the advantages and limitations of these sources in the literature.

Design/methodology/approach

To address the research aims, this study conducted a systematic literature review and content analysis of all relevant articles. Following the review, the methodological sections of the selected papers were examined to identify the characteristics and limitations of all data sources used in the papers.

Findings

This study revealed several limitations of the use of three major data sources, namely, web scraping with self-made bots, inside Airbnb and AirDNA, for sharing economy research. The review shows that the majority of the selected papers did not acknowledge any limitations, nor did they discuss the quality of the data sources.

Research limitations/implications

The findings of this paper can serve as guidelines for selecting appropriate data sources for research into the sharing economy and cautions researchers to address the limitations of the data sources used.

Originality/value

To the best of the authors’ knowledge, this is the first study that explores the advantages and limitations of data sources used in short-term rental market research.
Climate change adaptation strategies and technical efficiency of maize producers in Benin, West Africa
Authors: Akpa Armand Fréjuis , Amegnaglo Cocou Jaurès , Chabossou Augustin Foster
Published: May 2023

Purpose

This study aims to discuss climate change, by modifying the timing of several agricultural operations, reduce the efficiency and yield of inputs leading to a lower production level. The reduction of the effects of climate change on production yields and on farmers' technical efficiency (TE) requires the adoption of adaptation strategies. This paper analyses the impact of climate change adaptation strategies adopted on maize farmers' TE in Benin.

Design/methodology/approach

This paper uses an endogeneity-corrected stochastic production frontier approach based on data randomly collected from 354 farmers located in three different agro-ecological zones of Benin.

Findings

Estimation results revealed that the adoption of adaptation strategies improve maize farmers' TE by 1.28%. Therefore, polices to improve farmers' access to climate change adaptation strategies are necessarily for the improvement of farmers' TE and yield.

Research limitations/implications

The results of this study contribute to the policy debate on the enhancement of food security by increasing farmers' TE through easy access to climate change adaptation strategies. The improvement of farmers' TE will in turn improve the livelihoods of the communities and therefore contribute to the achievement of Sustainable Development Goals 1, 2 and 13.

Originality/value

This study contributes to theoretical and empirical debate on the relationship between adaptation to climate change and farmers' TE. It also adapts a new methodology (endogeneity-corrected stochastic production frontier approach) to correct the endogeneity problem due to the farmers' adaptation decision.