bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACTIntroduction: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

AbstractAlzheimer’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

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

AbstractNon-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

AbstractMeloidogyne 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

AbstractLipofuscin, 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

SummaryPatched 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.HiglightsDifferentiation of human iPSC into cerebellar organoidsHomozygous LOF ofPTCH1prevents cerebellar organoid differentiationPTCH1+/-cerebellar organoids display tissue-specific effects of SHH signallingEarly 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

AbstractMultiple 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

AbstractWhen 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 & NoteworthyThis 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

ABSTRACTSchistosomiasis 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

AbstractOvergeneralization 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 summaryAcute 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

AbstractWhile 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

AbstractFrontal 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.