bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constructing the brief Diagnostic Criteria for Temporomandibular Disorders (bDC/TMD)
Authors: Durham Justin , Ohrbach Richard , Baad-Hansen Lene , Davies Stephen , De Laat Antoon , Goncalves Daniela Godoi , Gordan Valeria V , Goulet Jean-Paul , Häggman-Henrikson Birgitta , Horton Michael ,   INfORM, Koutris Michail , Law Alan , List Thomas , Lobbezoo Frank , Michelotti Ambra , Nixdorf Donald R. , Oyarzo Juan Fernando , Peck Chris , Penlington Chris , Raphael Karen G. , Santiago Vivian , Sharma Sonia , Svensson Peter , Visscher Corine M. , Yoshiki Imamura , Alstergren Per 
Published: August 2023

AbstractBackgroundDespite advances in Temporomandibular disorders’ (TMDs) diagnosis, the diagnostic process continues to be problematic in non-specialist settings.ObjectiveTo complete a Delphi process to shorten the Diagnostic Criteria for TMD (DC/TMD) to a brief DC/TMD (bDC/TMD) for the diagnoses with the most utility in general dentistry settings.MethodsA international Delphi panel was created with 23 clinicians representing major specialities, general dentistry, and related fields. The process comprised a full day workshop, four virtual meetings, six rounds of electronic discussion, and finally an open consultation at a virtual international symposium.ResultsWithin the physical axis (Axis 1) the self-report Symptom Questionnaire of the DC/TMD did not require shortening from 14 items for the bDC/TMD. The compulsory use of the TMD pain screener was removed reducing the total number of Axis 1 items by 18%. The DC/TMD Axis 1 10-section examination protocol (25 movements, up to 12 sets of bilateral palpations) was reduced to 4 sections in the bDC/TMD protocol involving 3 movements and 3 sets of palpations. Axis I then resulted in two groups of diagnoses: painful TMD (inclusive of secondary headache), and common joint-related TMD with functional implications. The Psychosocial Axis (Axis 2) was shortened to an ultra-brief 11 item assessment.ConclusionThe bDC/TMD represents a substantially reduced and likely expedited method to establish (grouping) diagnoses in TMDs. This may provide greater utility for settings requiring less granular diagnoses for the implementation of initial treatment, for example non-specialist general dental practice.
Profile of speech and cognitive impairments in a patient with moyamoya disease: a longitudinal case study
Authors: Pashkov A. , Filimonova E. , Martirosyan A. , Ovsyannikov K. , Gunenko G. , Moysak G. , Rzaev J. 
Published: August 2023

AbstractMoyamoya is a rare chronic brain vascular disease with a set of potential life-threatening consequences due to a high probability of stroke occurrence. Patients suffering from this disease are often presented with diverse and severe sensory, motor and cognitive deficits, which often lead to general inability to work and, in the most severe cases, to complete loss of self-serving skills and gross disturbance of vital homeostatic functions. Here we present a case of a patient with moyamoya disease, who has been dynamically observed over more than 4 years after the first manifestation of her symptoms. We have been tracking the appearance of patient’s new symptoms and resolution of existing ones after neurosurgical treatment (revascularization surgery) with in-depth neurological examination, neuropsychological assessment and fMRI/DTI sessions. This study represents one of the first attempts to rigorously estimate the patterns of deficits at different levels, connecting neural circuits affected by the disease to behavior. Our findings lend further support to the idea that revascularization surgery can improve cognitive performance and highlights the importance of long-term follow-up in understanding the effects of surgery on brain function.
Extended genome-wide association study employing the African Genome Resources Panel identifies novel susceptibility loci for Alzheimer’s Disease in individuals of African ancestry
Authors: Ray Nicholas R. , Kunkle Brian W. , Hamilton-Nelson Kara , Kurup Jiji T. , Rajabli Farid , Cosacak Mehmet I. , Kizil Caghan , Jean-Francois Melissa , Cuccaro Michael , Reyes-Dumeyer Dolly , Cantwell Laura , Kuzma Amanda , Vance Jeffery M. , Gao Sujuan , Hendrie Hugh C. , Baiyewu Olusegun , Ogunniyi Adesola , Akinyemi Rufus O. ,   Alzheimer’s Disease Genetics Consortium, Lee Wan-Ping , Martin Eden R. , Wang Li-San , Beecham Gary W. , Bush William S. , Farrer Lindsay A. , Haines Jonathan L. , Byrd Goldie S. , Schellenberg Gerard D. , Mayeux Richard , Pericak-Vance Margaret A. , Reitz Christiane 
Published: August 2023

ABSTRACTINTRODUCTIONDespite a two-fold increased risk, individuals of African ancestry have been significantly underrepresented in Alzheimer’s Disease (AD) genomics efforts.METHODSGWAS of 2,903 AD cases and 6,265 cognitive controls of African ancestry. Within-dataset results were meta-analyzed, followed by gene-based and pathway analyses, and analysis of RNAseq and whole-genome sequencing data.RESULTSA novel AD risk locus was identified inMPDZon chromosome 9p23 (rs141610415, MAF=.002,P=3.68×10−9). Two additional novel common and nine novel rare loci approached genome-wide significance atP<9×10−7. Comparison of association and LD patterns between datasets with higher and lower degrees of African ancestry showed differential association patterns at chr12q23.2 (ASCL1), suggesting that the association is modulated by regional origin of local African ancestry.DISCUSSIONIncreased sample sizes and sample sets from Africa covering as much African genetic diversity as possible will be critical to identify additional disease-associated loci and improve deconvolution of local genetic ancestry effects.
A predictive model of ebolavirus spillover incorporating change in forests and human populations across spatial and temporal scales
Authors: Telford Carson T. , Amman Brian R. , Towner Jonathan S. , Bowden Sarah , Montgomery Joel M. , Lessler Justin , Shoemaker Trevor 
Published: August 2023

AbstractPast research has found associations between ebolavirus spillover and forest loss and fragmentation, although most predictions of the spatial distribution of ebolaviruses have not utilized these data. Spatial and temporal scales of covariate data measurement have also not previously been accounted for in predictive models of ebolavirus spillover, making it difficult to account for variables that influence ebolavirus transmission dynamics, such as movement and interaction of human and animal populations, trade, and animal behavioral responses to human presence and a changing environment. Using annual data on forest cover, forest loss and fragmentation, human population distribution, and meteorological variables, we developed models of ebolavirus spillover events from 2001-2021 to estimate the annual relative odds of ebolavirus spillover in equatorial Africa in 2021 and 2022. Analyses were done separately for all ebolavirus species (All-species analysis) and Zaire ebolavirus alone (Zaire-only analysis). Locations with the highest estimated relative odds of spillover occurred in patches throughout Democratic Republic of the Congo (DRC), Republic of the Congo, Gabon, Cameroon, and coastal west Africa in a spatial trend that resembled that of maps of forest fragmentation and forest loss. Reduced analyses that ignored forest loss and fragmentation data produced estimates that were distinct from the full analyses, highlighting locations where forest loss and fragmentation drove model predictions, which included coastal west Africa, southern Cameroon, and parts of DRC. Estimated spillover odds and increase in spillover odds at 2022 spillover sites ranked among the highest in equatorial Africa, suggesting the potential of predictive analyses to prioritize locations for surveillance and research efforts.SignificanceUsing annually updated data on forest change, human population distribution, and meteorological conditions, we developed models to estimate the relative odds of ebolavirus spillover in 2021 and 2022 in equatorial Africa, identifying locations with elevated odds of spillover and temporal shifts in spillover odds between the two years. Locations were identified whose estimates of spillover odds were driven by forest change. During 2022, two ebolavirus spillover events were identified in locations with elevated spillover odds estimates. Annually updated estimates of ebolavirus spillover can guide public health surveillance programs to high-risk locations at specific times, and guide potential ebolavirus reservoir sampling efforts to locations that recently experienced increases in spillover odds.
Krasloss of heterozygosity promotes MAPK dependent pancreatic ductal adenocarcinoma and induces therapeutic sensitivity
Authors: Fey Sigrid K. , Najumudeen Arafath K. , Ford Catriona , Gilroy Kathryn , Upstill-Goddard Rosie , Chang David K. , Clark William , Nixon Colin , Barry Simon T. , Morton Jennifer P. , Campbell Andrew D. , Sansom Owen J. 
Published: August 2023

AbstractPancreatic cancer is characterised by the prevalence of oncogenic mutations inKRAS. Previous studies have reported that alteredKrasgene dosage drives progression and metastatic incidence in pancreatic cancer. While the role of oncogenicKRASmutation is well characterised, the relevance of the partnering wild-typeKRASallele in pancreatic cancer is less well understood and controversial. Usingin vivomouse modelling of pancreatic cancer, we demonstrate that wild-typeKrasrestrains the oncogenic impact of mutantKras, and drastically impacts bothKras-mediated tumourigenesis and therapeutic response. Mechanistically, deletion of wild-typeKrasincreases oncogenicKrassignalling through the downstream MAPK effector pathway, driving pancreatic intraepithelial neoplasia (PanIN) initiation. In addition, in the KPC mouse model, a more aggressive model of pancreatic cancer, loss of wild-type KRAS leads to accelerated initiation but delayed tumour progression. These tumours had altered stroma, downregulatedMyclevels and an enrichment for immunogenic gene signatures. Importantly, loss of wild-typeKrassensitisesKrasmutant tumours to MEK1/2 inhibition though tumours eventually become resistant and then rapidly progress. This study demonstrates the repressive role of wild-typeKrasduring pancreatic tumourigenesis and highlights the critical impact of the presence of wild-type KRAS on tumourigenesis and therapeutic response in pancreatic cancer.
A deep genetic analysis of banana Fusarium wilt pathogens of Cuba in a Latin American and Caribbean diversity landscape
Authors: de la Parte Einar Martínez , Pérez-Vicente Luis , Torres David E. , van Westerhoven Anouk , Meijer Harold J. G. , Seidl Michael F. , Kema Gert H. J. 
Published: August 2023

SUMMARYFusarium wilt of bananas (FWB) is a devastating plant disease that causes significant economic losses in banana production worldwide and is one of the major concerns for Cuban banana cultivation. The disease is caused by members of the soil-borneFusarium oxysporumspecies complex. However, the genetic diversity amongFusariumspecies infecting bananas in Cuba is currently unknown.We conducted a comprehensive survey of symptomatic banana plants across all production zones of the country and assembled a collection of 170Fusariumisolates. Using genotyping- by-sequencing and whole-genome comparisons, we investigated the genetic diversity across this suite of isolates and compared it with the genetic diversity of a globalFusariumpanel.Typical FWB symptoms were observed in varieties of the Bluggoe cooking banana and Pisang Awak subgroups in 14 provinces. Phylogenetic analysis revealed thatF. purpurascens, F. phialophorum,andF. tardichlamydosporumcause FWB in Cuba, with the latter dominating the population. Furthermore, we identified between five and seven genetic clusters, withF. tardichlamydosporumisolates divided into at least two distinct subgroups, indicating a high genetic diversity ofFusariumspp. causing FWB in the Americas.Our study provides unprecedented insights into the population genetic structure and diversity of the FWB pathogen in Cuba and the Latin American and Caribbean regions.
Lysosomal MLKL is balanced by ESCRT to control cell death
Authors: Jamard Catherine , Gil Clara , Castets Marie , Ichim Gabriel , Weber Kathrin 
Published: August 2023

AbstractMixed lineage kinase-like (MLKL) is activated by RHIM-domain containing kinase (RIPK)3 to permeabilize the plasma-membrane and execute necroptosis, a form of regulated necrosis. We found that MLKL is activated in an atypical, RIPK3- and necroptosis-independent manner downstream of Toll-like receptor 3, resulting in its translocation to lysosomes and lysosomal membrane permeabilization. Damaged lysosomes then undergo exocytosis, leading to the integration of lysosomal MLKL into the plasma-membrane to trigger cell death. The ESCRT-machinery can repair damaged lysosomes and counteract cell death by packing lysosomal MLKL into intraluminal vesicles, which are subsequently released as extracellular vesicles. In this way, ESCRT-machinery balances life and death decisions by preventing lysosomal MLKL to reach its killing destination, which is the plasma-membrane.
Insights into Digit Evolution from a Fate Map Study of the Forearm
Authors: Oh JDH , Saunders DDZ , McTeir L , Jackson M , Glover JD , Schoenebeck JJ , Lettice LA , Davey MG 
Published: August 2023

AbstractThe cellular and genetic networks which contribute to the development of the zeugopod, (radius and ulna of the forearm, tibia and fibula of the leg) are not well understood, although these bones are susceptible to loss in congenital human syndromes and to the action of teratogens such as thalidomide. Using a new fate mapping approach in transgenic chickens, we show that there is a small contribution ofSHHexpressing cells to the posterior ulna, posterior carpals and digit 3. We establish that while the majority of the ulna develops in response to paracrine SHH signaling in both the chicken and mouse, there are differences in the contribution ofSHHexpressing cells to other tissues of the zeugopod between these two species as well as between the chicken ulna and fibula. This is evidence that although zeugopod bones are clearly homologous according to the fossil record, the zeugopod bones of the wing and leg are formed by subtly different signalling and patterning events during embryonic development, which can be used to understand the shaping of the bird wing skeleton during the evolution of powered flight.
Molecular Mechanism of PP2A/B55α Phosphatase Inhibition by IER5
Authors: Cao Ruili , Jones Daniel TD , Pan Li , Yang Annie , Wang Shumei , Padi Sathish K. R. , Shaun Rawson , Aster Jon C , Blacklow Stephen C 
Published: August 2023

ABSTRACTPP2A serine/threonine phosphatases are heterotrimeric complexes that execute many essential physiologic functions. These activities are modulated by additional regulatory proteins, such as ARPP19, FAM122A, and IER5. Here, we report the cryoelectron microscopy structure of a complex of PP2A/B55α with the N-terminal structured region of IER5 (IER5-N50), which occludes a surface on B55α used for substrate recruitment, and show that IER5-N50 inhibits PP2A/B55α catalyzed dephosphorylation of pTau in biochemical assays. Mutations of full-length IER5 that disrupt its PP2A/B55α interface interfere with co-immunoprecipitation of PP2A/B55α. These mutations and deletions that remove the nuclear localization sequence of IER5 suppress cellular events such asKRT1expression that depend on association of IER5 with PP2A/B55α. Querying the Alphafold2 predicted structure database identified SERTA domain proteins as high-confidence PP2A/B55α-binding structural homologs of IER5-N50. These studies define the molecular basis of PP2A/B55α inhibition by IER5-family proteins and suggest a roadmap for selective pharmacologic modulation of PP2A/B55α complexes.
A mutant fitness compendium in Bifidobacteria reveals molecular determinants of colonization and host-microbe interactions
Authors: Shiver Anthony L. , Sun Jiawei , Culver Rebecca , Violette Arvie , Wynter Charles , Nieckarz Marta , Mattiello Samara Paula , Sekhon Prabhjot Kaur , Friess Lisa , Carlson Hans K. , Wong Daniel , Higginbottom Steven , Weglarz Meredith , Wang Weigao , Knapp Benjamin D. , Guiberson Emma , Sanchez Juan , Huang Po-Hsun , Garcia Paulo A. , Buie Cullen R. , Good Benjamin , DeFelice Brian , Cava Felipe , Scaria Joy , Sonnenburg Justin , Van Sinderen Douwe , Deutschbauer Adam M. , Huang Kerwyn Casey 
Published: August 2023

AbstractBifidobacteria commonly represent a dominant constituent of human gut microbiomes during infancy, influencing nutrition, immune development, and resistance to infection. Despite interest as a probiotic therapy, predicting the nutritional requirements and health-promoting effects of Bifidobacteria is challenging due to major knowledge gaps. To overcome these deficiencies, we used large-scale genetics to create a compendium of mutant fitness inBifidobacterium breve(Bb). We generated a high density, randomly barcoded transposon insertion pool inBb, and used this pool to determineBbfitness requirements during colonization of germ-free mice and chickens with multiple diets and in response to hundreds ofin vitroperturbations. To enable mechanistic investigation, we constructed an ordered collection of insertion strains covering 1462 genes. We leveraged these tools to improve models of metabolic pathways, reveal unexpected host- and diet-specific requirements for colonization, and connect the production of immunomodulatory molecules to growth benefits. These resources will greatly reduce the barrier to future investigations of this important beneficial microbe.
Including organism and environmental heterogeneity in kinematic continuum models of collective behaviour with applications to locust foraging and group structure
Authors: Georgiou F. , Buhl J. , Green J.E.F. , Lamichhane B , Thamwattana N. 
Published: August 2023

AbstractCollective behaviour occurs at all levels of the natural world, from cells joining together to form complex structures, to locusts interacting to form large and destructive plagues. These complex behaviours arise from simple individual and environmental interactions, and thus lend themselves well to mathematical modelling. One simplifying assumption, that of relative homogeneity of organisms, is often applied to keep the mathematics tractable. However, heterogeneity arising due to the internal state of individuals has an impact on these interactions and thus plays a role in group structure and dynamics.In this paper, we introduce a continuum model that accounts for this heterogeneity in the form of a state space that models an organisms internal state and converts this to movement characteristics. Using a variety analytic techniques, we investigate the effect of internal state on aggregation density and aggregation formation behaviour, finding that density and formation is most affected by the ratio of attractive to dispersive interactions.We then apply the model to a concrete example of locust foraging to investigate the effect of food, hunger, and gregarisation on locust group formation and structure. Through numerical simulations we find that the most gregarious and satiated locusts tend to be located towards the centre of locust groups. Conversely, hunger drives locusts towards the edges of the group. Finally, we find that locust group dispersal may be driven in part by hunger.Author SummaryCollective behaviour occurs at all levels of the natural world, from cells joining together to form complex structures, to locusts interacting to form large and destructive plagues. We can modelling these complex behaviours using mathematical models however we often need to rely on simplifying assumptions to keep the mathematics easy enough to analyse. One simplifying assumption that is often employed is assuming that all the modelled organisms are the same (or in one of only a few possible states). However, this is often not the case in nature where the differences between individuals arising due to internal characteristics, such as hunger or age, often affects their behaviour and thus can change group dynamics.In this paper we introduce a mathematical model that is able to capture these differences and apply the newly developed model to locust foraging. We find that hunger tends to drive individuals to the edges of aggregations as well as lowers the maximum possible density. These two results combine to give a possible mechanism for the dispersal of locust groups.
Phylogeny and disease links of a widespread and ancient gut phage lineage
Authors: de Jonge Patrick A. , van den Born Bert-Jan H. , Zwinderman Aeilko H. , Nieuwdorp Max , Dutilh Bas E. , Herrema Hilde 
Published: August 2023

AbstractViruses are a core component of the human microbiome, impacting health and disease through interactions with gut bacteria1and the immune system2. Most viruses in the human microbiome are bacteriophages, which exclusively infect bacteria. Individual gut bacteriophages can affect bacterial bile acid deconjugation3, and can alter their infection strategy based on dietary content4. Up to recently, most studies of the gut virome have focused on low taxonomic scales (e.g., viral operational taxonomic units), hampering population-level analyses. We previously identified the expansive and widespread CandidatusHeliusviridaebacteriophage family in a cohort with inhabitants of Amsterdam, the Netherlands. Here, we study their biodiversity and evolution in a wide variety of human populations. With a detailed phylogeny based on sequences from six viral genome databases, we now propose the Candidatus orderHeliusviralesto accommodate these viruses. We identifyCa. Heliusviralesviruses in 80% of 5,441 individuals across 39 studies, and also in nine out of thirteen analyzed metagenomes from ancient humans that lived in Europe and North America between 1,000 and 5,000 years ago. We show that a largeCa. Heliusviraleslineage has diversified starting at the appearance ofHomo sapienssome 200,000-300,000 years ago. Ancient peoples and modern hunter-gatherers further have distinctCa. Heliusviralespopulations that are characterized by lower richness than modern urbanized people. Within urbanized people, those suffering from type 1 and type 2 diabetes, as well as inflammatory bowel disease, have higherCa. Heliusviralesrichness than healthy controls. We thus conclude that these ancient core members of the human gut virome have thrived with increasingly westernized lifestyles of the human population.
A short sequence in the tail of SARS-CoV-2 envelope protein controls accessibility of its PDZ Binding Motif to the cytoplasm
Authors: Neitthoffer Benoit , Alvarez Flavio , Larrous Florence , Saguy Célia Caillet , Manneville Sandrine Etienne , Boëda Batiste 
Published: August 2023

AbstractThe carboxy terminal tail of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) envelope protein (E) contains a PDZ-binding motif (PBM) which is crucial for coronavirus pathogenicity. During SARS-CoV-2 infection, the viral E protein is expressed within the Golgi apparatus membrane of host cells with its PBM facing the cytoplasm. In this work we study the molecular mechanisms controlling the presentation of the PBM to host PDZ (PSD-95/Dlg/ZO-1) domain-containing proteins. We show that at the level of the Golgi apparatus, the PDZ-binding motif of the E protein is not detected by E C-terminal specific antibodies neither by PDZ domain-containing protein binding partner. Four alanine substitutions upstream of the PBM in the central region of the E protein tail is sufficient to generate immunodetection by anti-E antibodies and trigger robust recruitment of the PDZ domain-containing protein into the Golgi organelle. Overall, this work suggests that the presentation of the PBM to the cytoplasm is under conformational regulation mediated by the central region of the E protein tail and that PBM presentation probably does not occur at the surface of Golgi cisternae but likely at post-Golgi stages of the viral cycle.