bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized sham-controlled trial of transcranial and intranasal photobiomodulation in Japanese patients with mild cognitive impairment and mild dementia due to Alzhimer’s disease: a protocol
Authors: Yokoi Yuma , Inagawa Takuma , Yamada Yuji , Matsui Makoto , Tomizawa Asumi , Noda Takamasa 
Published: December 2023

ABSTRACTIntroductionPhotobiomodulation (PBM) is a novel strategy for cognitive enhancement by improving brain metabolism and blood flow. It is potentially beneficial for patients with Alzheimer’s disease (AD). We present a study protocol for a randomised controlled trial designed to evaluate the efficacy and safety of PBM.Method and analysisThis is a single-centre, parallel-group, randomised, sham-controlled study. We enrol patients with mild cognitive impairment or dementia due to AD and assigned them to receive either active or sham stimulation at home for 12 weeks, with three sessions per week (20 minutes each). The stimulation involves invisible near-infrared light delivered by five applicators (one in a nostril, one on the frontal scalp, and three on the occipital scalp). The primary outcome will be the mean change in the Alzheimer Disease Assessment Scale–cognition from baseline to Week 12. We will also measure cognitive function, activity of daily living, behavioural and psychological symptoms, and caregiver burden. We will collect data at clinics at baseline and Week 12 and remotely at home. We estimate a sample size of 30 (20 active and 10 sham) based on an expected mean difference of −6.9 and an SD of 4.8. We use linear models for the statistical analysis.Ethics and disseminationThe National Center of Neurology and Psychiatry Clinical Research Review Board (CRB3200004) approved this study. The results of this study will be published in a scientific peer-reviewed journal.Trial registration details Japan Registry of Clinical Trials jRCTs032230339.ARTICLE SUMMARYStrengths and limitations of this studyThis study aims to investigate the impact of PBM on the cognitive function and quality of life of patients diagnosed with mild cognitive impairment or dementia, using a well-defined sample population.A potential limitation of this study is that it is conducted at a single centre and does not adequately assess the long-term outcomes of PBM.
Optimizing Glycemic Control in Type 1 Diabetic Patients using a Deep Learning-Based Artificial Pancreas with a Secure Glucagon and Insulin Delivery System
Authors: Singh Rohan , Rao Raj R. 
Published: December 2023

AbstractType 1 diabetes impacts millions worldwide, with some patients facing rapid fluctuations in their blood sugar levels. These fluctuations can negatively impact an individual’s quality of life and if untreated, can lead to nerve damage, coma, and death. While current methods have helped address hyperglycemia (high blood sugar), there has been less success with hypoglycemia (low blood sugar) and glucagon administration. To bridge this gap, an artificial pancreas with a novel insulin and glucagon pump was developed. Initiating the system, a personalized mobile app enables users to input meal carbohydrate and insulin bolus data. The data is then transmitted to a deep learning model that incorporates Continuous Glucose Monitor readings, along with carbohydrate and insulin data from the app. The two-layer Long Short-Term Memory network, developed in Python, accurately forecasts blood sugar levels on Ohio University’s OhioT1DM patient dataset and the UVa/Padova simulation’s data for a 30 minute-interval. An algorithm then utilizes the predictions to calculate optimal insulin and glucagon doses using metabolization formulas. To ensure system security, data is transmitted through a cloud-based MQ Telemetry Transport server and secured with industry-standard authentication and encryption methods. Finally, a microcontroller-based prototype accurately dispenses insulin and glucagon doses. The system kept in-silico patients at optimal levels for 38% longer and reduced dangerous levels by 22% compared to conventional controllers on an FDA-approved preclinical trial alternative simulation. By addressing both hypo and hyperglycemia, this real-time medical device can be a transformative tool for individuals with diabetes, enabling them to live healthier and more fulfilling lives.
BRI1-mediated removal of seed coat H3K27me3 marks is a brassinosteroid-independent process
Authors: Pankaj Rishabh , Lima Rita B. , Luo Guan-Yu , Ehlert Sinah , del Toro-de León Gerardo , Bente Heinrich , Finger Pascal , Sato Hikaru , Figueiredo Duarte D. 
Published: December 2023

AbstractSeed development in angiosperms starts with double fertilization, where two paternal sperm cells fertilize the maternal gametes. This leads to the formation of the embryo and of the endosperm. These fertilization products are enveloped by the maternally-derived seed coat, the development of which is inhibited prior to fertilization by the Polycomb Repressive Complex 2 (PRC2). This complex deposits the repressive histone mark H3K27me3, whose removal is necessary for seed coat formation. Here, we show that JUMONJI-type (JMJ) histone demethylases are expressed in the seed coats ofArabidopsis thaliana(Arabidopsis) and are necessary for its formation. We propose that JMJ activity is coupled to Brassinosteroid (BR) function, as BR effectors physically recruit JMJ proteins to target loci. Consistent with this, we show that loss of BR biosynthesis and signaling leads to seed coat defects, and that loss of the main BR receptor, BRI1, results in H3K27me3 hypermethylation. Moreover, our data points to BRI1 mediating H3K27me3 removal independently of BRs, while a different receptor, BRL3, likely regulates seed coat formation in a BR-dependent manner. We thus propose a model where seed coat development relies on canonical and non-canonical functions of BR receptors.
Specific inhibition of α-synuclein oligomer generation and toxicity by the chaperone domain Bri2 BRICHOS
Authors: Adam Laurène , Kumar Rakesh , Arroyo-Garcia Luis Enrique , Molenkamp Willem Hendrik , Nowak Jan Stanislaw , Klute Hannah , Farzadfard Azad , Alkenayeh Rami , Nielsen Janni , Biverstål Henrik , Otzen Daniel E. , Johansson Jan , Abelein Axel 
Published: December 2023

ABSTRACTUnderstanding the molecular mechanisms of neurodegenerative diseases and finding efficient treatments have been major priorities for research and society, yet new therapeutic approaches remain essential to face the socio-economic burden caused by these devastating diseases. Protein misfolding and aggregation are involved in several neurodegenerative disorders, such as α-synuclein (αSyn) implicated in Parkinson’s disease. Elucidating the microscopic nucleation mechanisms has opened new opportunities to develop therapeutics against toxic mechanisms and species. Here, we show that naturally occurring molecular chaperones, represented by the anti-amyloid Bri2 BRICHOS domain, can be used to target αSyn-associated nucleation processes and structural species related to neurotoxicity. Our findings revealed that BRICHOS predominately suppresses the formation of new nucleation units on the fibrils surface (secondary nucleation), in addition to fibril-end elongation. This mechanism implies a drastic decrease of the oligomer generation rate. Besides targeting secondary nucleation sites on the fibril surface, BRICHOS directly binds to oligomeric αSyn species. Further, usingex vivoexperiments, BRICHOS effectively diminishes αSyn fibril-related toxicity to hippocampal electrophysiology. Our studies show that molecular chaperones can be utilized as tools to target molecular processes and structural species related to αSyn neurotoxicity and have the potential as protein-based treatments against neurodegenerative disorders.
Dynamic Plasticity Systems Direct Early Adaptation to Treatment in Neuroblastoma
Authors: Roux Cecilia , Hamer Sian , Shea Abigail , Chen Emilia , Sadr Ayeh Sadat , English Christie , Sahoo Sarthak , Allo Anido Alejandro , Che Harvey , Chesler Louis , Jolly Mohit Kumar , Morgan Michael David , Bruna Alejandra 
Published: December 2023

AbstractIn paediatric cancers like neuroblastoma, limited genetic diversity emphasizes the role of phenotypic heterogeneity in driving malignancy. We investigated this phenomenon using experimental evolution and single-cell techniques in neuroblastoma preclinical models. Our findings reveal that neuroblastoma cells navigate multistable phenotypic landscapes, named plasticity systems. These finely regulate their topology and dynamics enabling tolerance, persistence, and regrowth in response to treatment. While preferential killing of adrenergic cells (ADRN), notably under cisplatin treatment, enriches drug-tolerant persister (DTP) populations with mesenchymal (MES) properties, we also observed phenotypic transitions contributing to DTP entry and exit. Additionally, single-cell-derived clone experiments unveiled a spectrum of heritable plasticity traits linked to functional properties, influencing DTP behaviour. Mathematical modelling supports the critical role of all cell phenotypes in evolutionary adaptation. Collectively, our study depicts plasticity systems as key early cancer drivers of adaptive evolution in neuroblastoma through regulating the multistability and dynamics of phenotypic landscapes. These insights underscore the necessity of decoding plasticity for advancing long-term therapeutic effectiveness.
Nanos2+cells give rise to germline and somatic lineages in the sea anemoneNematostella vectensis
Authors: Denner Andreas , Steger Julia , Ries Alexander , Morozova-Link Elizaveta , Ritter Josefine , Haas Franziska , Cole Alison G. , Technau Ulrich 
Published: December 2023

AbstractIn all animals, stem cell populations of varying potency facilitate regeneration and tissue homeostasis. Notably, germline stem cells in both vertebrates and invertebrates express highly conserved RNA-binding proteins, such asnanos, vasaandpiwi. Interestingly, in animals, which are capable of whole-body regeneration, such as poriferans, hydrozoans and planarians, these genes are also expressed in somatic multi- and pluripotent stem cells, which led to the proposal that they had an ancestral role in all stem cells. While multi- and pluripotent interstitial stem cells have been identified in hydrozoans, they have not unambiguously been demonstrated in other cnidarian classes. Therefore, it is currently unclear if these stem cell systems share a common evolutionary origin or have been adapted individually in different lineages as homoplasy. We therefore aimed to characterize stem cells expressing conserved stem cell marker genes in the sea anemoneNematostella vectensis, to gain insight of shared traits governing the regulation of this enigmatic cell type. Through single cell transcriptomics, we identify cell populations expressing the germline associated markerspiwi1andnanos2in the soma and germline. Transgenic reporter genes reveal a lineage giving rise to somatic cells, consistent with a role as a multipotent stem cell population. Cell proliferation studies show that a fraction ofnanos2+reporter cells are cycling and CRISPR/Cas9 mediated gene knockout show thatnanos2+progenitor cells are indispensable for male and female germline maintenance inNematostella. This suggestsnanosandpiwigenes have a conserved role in somatic and germline stem cells in cnidarians.
An improved haplotype resolved genome reveals more rice genes
Authors: Abdullah Muhammad , Furtado Agnelo , Masouleh Ardashir Kharabian , Okemo Pauline , Henry Robert 
Published: December 2023

AbstractThe rice reference genome (Oryza sativa ssp. japonica cv. Nipponbare) has been an important resource in plant science. We now report an improved and haplotype resolved genome sequence based upon more accurate sequencing technology. This improved assembly includes regions missing in earlier genomes sequences and the annotation of more than 3,000 new genes due to greater sequence accuracy.
Application of slow-controlled release fertilizer coordinates the carbon flow in carbon-nitrogen metabolism to effect rice quality
Authors: Jiang Zhengrong , Chen Qiuli , Liu Dun , Tao Weike , Gao Shen , Li Jiaqi , Lin Chunhao , Zhu Meichen , Ding Yanfeng , Li Weiwei , Li Ganghua , Sakr Soulaiman , Xue Lihong 
Published: December 2023

AbstractSlow-controlled release fertilizers are experiencing a popularity in rice cultivation due to their effectiveness in yield and quality with low environmental costs. However, the underlying mechanism by which these fertilizers regulate grain quality remains inadequately understood. This study investigated the effects of five fertilizer management practices on rice quality in a two-year field experiment: CK, conventional fertilization, and four applications of slow-controlled release fertilizer (UF, urea formaldehyde; SCU, sulfur-coated urea; PCU, polymer-coated urea; BBF, controlled-release bulk blending fertilizer). In 2020 and 2021, the yields of UF and SCU groups showed significant decreases when compared to conventional fertilization, accompanied by a decline in nutritional quality. Additionally, PCU group exhibited poorer cooking and eating qualities. However, BBF group achieved increases in both yield (10.8 t hm−2and 11.0 t hm−2) and grain quality reaching the level of CK group. The sufficient nitrogen supply in both the PCU and BBF groups during the grain-filling stage led to a greater capacity for the accumulation of proteins and amino acids in the PCU group compared to starch accumulation. Intriguingly, BBF group showed better carbon-nitrogen metabolism than that of PCU group. The optimal nitrogen supply present in BBF group suitable boosted the synthesis of amino acids involved in the glycolysis/ tricarboxylic acid cycle, thereby effectively coordinating carbon-nitrogen metabolism. The application of the new slow-controlled release fertilizer, BBF, is advantageous in regulating the carbon flow in the carbon-nitrogen metabolism to enhance rice quality.
dAux orchestrates the phosphorylation-dependent assembly of the lysosomal V-ATPase in glia and contributes to α-synuclein degradation
Authors: Zhang Shiping , Wang Linfang , Yi Shuanglong , Tsai Yu-ting , Wang Honglei , Li Shuhua , Wang Ruiqi , Liu Yang , Yan Wei , Liu Chang , He Kai-Wen , Ho Margaret S. 
Published: December 2023

AbstractGlia serve as double-edged swords to modulate neuropathology in Parkinson’s disease (PD), but how they react opposingly to be beneficial or detrimental under pathological conditions, like promoting or eliminating α-synuclein (α-syn) inclusions, remains elusive. Here we present evidence that dAuxilin (dAux), theDrosophilahomolog of the PD risk factor Cyclin G-associated kinase (GAK), regulates the lysosomal degradation of α-syn in glia. Lack of glial Gak/dAux increases the lysosome number and size, regulates lysosomal acidification and hydrolase activity, and ultimately blocks the degradation of substrates including α-syn. Whereas α-syn accumulated prominently in lysosomes devoid of glial dAux, levels of injected α-syn preformed fibrils also further enhanced in the absence of microglial Gak. Mechanistically, dAux mediates phosphorylation at the serine 543 of Vha44, the V1C subunit of the vacuolar H+-ATPase (V-ATPase), regulates its assembly to control proper acidification of the lysosomal milieu. Expression of Vha44, but not the Vha44 variant lacking S543 phosphorylation, restores lysosome acidity, locomotor deficits, and DA neurodegeneration upon glial dAux depletion, linking this pathway to PD. Our findings identify a phosphorylation-dependent switch controlling the V-ATPase assembly for lysosomal α-syn degradation in glia. Targeting the clearance of glial α-syn inclusions via this lysosomal pathway could potentially be a therapeutical approach to ameliorate the disease progression in PD.
Development of Pial Collaterals by Extension of Pre-existing Artery Tips
Authors: Kumar Suraj , Ghosh Swarnadip , Shanavas Niloufer , Sivaramakrishnan Vinayak , Dwari Manish , Das Soumyashree 
Published: December 2023

SUMMARYPial collaterals provide protection from ischemic damage and improve prognosis of stroke patients. The origin or precise sequence of events underlying pial collateral development is unclear and has prevented clinicians from adapting new vascularization and regeneration therapies. We use genetic lineage tracing and intra-vital imaging of mouse brains at cellular resolution to show that during embryogenesis, pial collateral arteries develop from extension and anastomoses of pre-existing artery tips, in a VegfR2 dependent manner. This process of artery tip extension occurs on pre-determined microvascular tracks. Our data demonstrate that an arterial receptor, Cxcr4, earlier shown to drive artery cell migration and coronary collateral development, is dispensable for formation and maintenance of pial collateral arteries. Our study shows that collateral arteries of the brain are built by a unique mechanism, distinct from that of the heart.
Developmental arcs of plasticity in whole movement repertoires of a clonal fish
Authors: Ehlman Sean M. , Scherer Ulrike , Bierbach David , Stärk Luka , Beese Marvin , Wolf Max 
Published: December 2023

AbstractDevelopmental plasticity at the behavioral repertoire level allows animals to incrementally adjust their behavioral phenotypes to match their environments through ontogeny, serving as a lynchpin between ecological factors that cue phenotypic adjustments and evolutionary forces that select upon emergent phenotypic variation. Quantifying the continuous arcs of plasticity throughout animals’ development, however, has often been prohibitively challenging. Here, we leverage recent advancements in high-resolution behavioral tracking and analysis to (i) track the behavior of 45 genetically identical fish clones (Poecilia formosa) reared in near-identical environments during their first four weeks of life at 0.2 s resolution and (ii) quantify the continuous arcs of plasticity across entire behavioral repertoires through development. Doing so, we are able to test one of the most fundamental theoretical predictions from Bayesian models of development that in stable (but initially unknown) environments, behavioral plasticity should gradually decrease from a maximum at the beginning of life. Using two approaches to measure plasticity across ontogeny, we first quantify plasticity in individual behavioral metrics before also developing a novel whole-repertoire approach that calculates plasticity as the degree of ‘behavioral entropy’ across a multi-dimensional behavioral phenotype space. We robustly find – despite experimentally matching as best as possible the assumptions of models that predict decreasing plasticity – a ∼two-week initial increase in plasticity in movement behaviors before plasticity subsequently decreased. Our results challenge a common intuition about the optimal developmental course of plasticity through early ontogeny, thereby also demonstrating the value of long-term behavioral tracking approaches for testing fundamental predictions on phenotypic development.Significance statementBehavioral plasticity across development may help animals adjust to uncertainty in moderately unpredictable environments. In stable environments, developing animals should gradually decrease this uncertainty through ontogeny, becoming less sensitive to incoming information (and thus less behaviorally plastic) as they age. This intuitive expectation of ‘old dog’ inflexibility to ‘new tricks’, however, has not been adequately tested with the long-term, highresolution datasets that would be ideal. Here, we achieve such a test and emphasize the significance of this study in (1) providing a novel method for quantifying multi-dimensional behavioral plasticity continuously across long-term, high-resolution behavioral timeseries and in (2) testing fundamental theory that links the temporal patterning of environmental conditions to evolved patterns of behavioral plasticity across development.
Clustering of HR+/HER2- breast cancer in an Asian cohort is driven by immune phenotypes
Authors: Pan Jia-Wern , Ragu Mohana , Chan Wei-Qin , Hasan Siti Norhidayu , Islam Tania , Teoh Li-Ying , Jamaris Suniza , See Mee-Hoong , Yip Cheng-Har , Rajadurai Pathmanathan , Looi Lai-Meng , Mohd Taib Nur Aishah , Rueda Oscar M. , Caldas Carlos , Chin Suet-Feung , Lim Joanna , Teo Soo Hwang 
Published: December 2023

AbstractBreast cancer exhibits significant heterogeneity, manifesting in various subtypes that are critical in guiding treatment decisions. This study aimed to investigate the existence of distinct subtypes of breast cancer within the Asian population, by analysing the transcriptomic profiles of 934 breast cancer patients from a Malaysian cohort. Our findings reveal that the HR+/HER2-breast cancer samples display a distinct clustering pattern based on immune phenotypes, rather than conforming to the conventional luminal A-luminal B paradigm previously reported in breast cancers from women of European descent. This suggests that the activation of the immune system may play a more important role in Asian HR+/HER2-breast cancer than has been previously recognized. Analysis of somatic mutations by whole exome sequencing showed that counter-intuitively, the cluster of HR+/HER2-samples exhibiting higher immune scores was associated with lower tumour mutational burden, lower homologous recombination deficiency scores, and fewer copy number aberrations, implicating the involvement of non-canonical tumour immune pathways. Further investigations are warranted to determine the underlying mechanisms of these pathways, with the potential to develop innovative immunotherapeutic approaches tailored to this specific patient population.
ganon2: up-to-date and scalable metagenomics analysis
Authors: Piro Vitor C. , Reinert Knut 
Published: December 2023

AbstractThe fast growth of public genomic sequence repositories greatly contributes to the success of metagenomics. However, they are growing at a faster pace than the computational resources to use them. This challenges current methods, which struggle to take full advantage of the massive and fast data generation. We propose a generational leap in performance and usability with ganon2, a sequence classification method that performs taxonomic binning and profiling for metagenomic analysis. It indexes large datasets with a small memory foot-print, maintaining fast, sensitive, and precise classification results. Based on the full NCBI RefSeq and its subsets, ganon2 indices are on average 50% smaller than state-of-the-art methods. Using 16 simulated samples from various studies, including the CAMI 1+2 challenge, ganon2 achieved up to 0.15 higher median F1-Score in taxonomic binning. In profiling, improvements in the F1-Score median are up to 0.35, keeping a balanced L1-norm error in the abundance estimation. ganon2 is one of the fastest tools evaluated and enables the use of larger, more diverse, and up-to-date reference sets in daily microbiome analysis, improving the resolution of results. The code is open-source and available with documentation athttps://github.com/pirovc/ganon.