bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidental but Not Insignificant: Thyroid Cancer in Patients with Graves Disease
Authors: Wang Rongzhi , Disharoon Mitchell , Song Zhixing , Gillis Andrea , Fazendin Jessica , Lindeman Brenessa , Chen Herbert , McMullin Jessica Liu 
Published: January 2024

BACKGROUND:
Graves disease is the most common cause of hyperthyroidism in the US. Treatment with antithyroid drugs and radioactive iodine is more commonly used than surgical management with total thyroidectomy (TTx). However, incidentally discovered thyroid cancer (TC) has been described on surgical pathology from patients who underwent surgical treatment of Graves disease, which would be missed with these other treatment strategies. We sought to determine the incidence rate of TC among patients with surgically treated Graves disease.

STUDY DESIGN:
We retrospectively reviewed patients with Graves disease who underwent TTx at a single institution from 2011 to 2023. Pathology reports were reviewed for TC. Patient demographics, preoperative laboratory and radiological evaluations, preoperative medical management, and surgical outcomes were compared between patients with and without incidental TC.

RESULTS:
There were 934 patients, of whom 60 (6.4%) patients had incidentally discovered TC on pathology. The majority (58.3%) of patients had papillary thyroid carcinoma, followed by 33.3% with papillary microcarcinoma. Preoperative ultrasound (US) was obtained in 564 (60.4%) of patients, with 44.3% with nodules, but only 34 (13.7%) of those with nodules had TC on final pathology. Preoperative fine needle aspiration was obtained in 15 patients with TC, and 8 patients (53.3%) were reported as benign lesions, which ultimately had TC on final pathology. There was no difference in sex, race or ethnicity, preoperative medical management, and postoperative outcomes between the 2 groups.

CONCLUSIONS:
Incidental TC was found on surgical pathology in 6.4% of patients undergoing TTx for Graves disease. Preoperative imaging with US and fine needle aspiration were often unreliable at predicting TC. The incidence of TC should not be underestimated when counseling patients on definitive management for Graves disease.
An Integrated Machine Learning Approach Delineates an Entropic Expansion Mechanism for the Binding of a Small Molecule toα-Synuclein
Authors: Menon Sneha , Adhikari Subinoy , Mondal Jagannath 
Published: January 2024

AbstractThe mis-folding and aggregation of intrinsically disordered proteins (IDPs) such asα-synuclein (αS) underlie the pathogenesis of various neurodegenerative disorders. However, targetingαS with small molecules faces challenges due to its lack of defined ligand-binding pockets in its disordered structure. Here, we implement a deep artificial neural network based machine learning approach, which is able to statistically distinguish fuzzy ensemble of conformational substates ofαS in neat water from those in aqueous fasudil (small molecule of interest) solution. In particular, the presence of fasudil in the solvent either modulates pre-existing states ofαS or gives rise to new conformational states ofαS, akin to an ensemble-expansion mechanism. The ensembles display strong conformation-dependence in residue-wise interaction with the small molecule. A thermodynamic analysis indicates that small-molecule modulates the structural repertoire ofαS by tuning protein backbone entropy, however entropy of the water remains unperturbed. Together, this study sheds light on the intricate interplay between small molecules and IDPs, offering insights into entropic modulation and ensemble expansion as key biophysical mechanisms driving potential therapeutics.
Cerebral Blood Volume Modulates Glymphatic Influx Through Extra-ventricular Cerebrospinal Fluid Volume
Authors: Li Juchen , Liu Xingyue , Bo Binshi , Pei Mengchao , Zhang Kaiwei , Tong Chuanjun , Jiang Ming , Zhang Sheng , Li Yufeng , Cang Jing , Liang Zhifeng , Fang Fang 
Published: January 2024

AbstractThe glymphatic system facilitates waste removal via cerebrospinal fluid (CSF) influx alongside perivascular spaces throughout the brain. Vasomotion, the slow motion of blood vessel (0.1-0.3 Hz), has been found to be one of the driving forces for perivascular clearance, but it is not clear whether more chronical change of vessel diameter, as reflected by macroscopic cerebral blood volume (CBV), has any impact on glymphatic function. Combining multimodal mouse MRI techniques, we investigated the relationship among glymphatic influx, CBV, CSF volume and EEG power under six different conditions (awake, dexmedetomidine, isoflurane, isoflurane/dexmedetomidine, ketamine/xylazine and awake with caffeine). We found dexmedetomidine and caffeine enhanced glymphatic influx, while isoflurane reduced it compared with awake condition. Quantitative CBV imaging revealed that glymphatic influx was negatively correlated to CBV across the above conditions. Furthermore, such negative correlation was found to be mediated in part by changes of extra-ventricular CSF volume, which was quantified using T1 MRI. Taken together, our results suggest that CBV is a consciousness independent modulator of glymphatic function and modulates glymphatic influx through extra-ventricular CSF volume. This new finding opens potential avenues to enhance brain waste clearance by regulating CBV, which could be beneficial for protein deposition related neurological diseases.TeaserCBV is a consciousness independent modulator of glymphatic function and modulates glymphatic influx through extra-ventricular CSF volume.
Immunoinformatic approach to design CTL epitope based chimeric vaccine targeting multiple serotypes of dengue virus
Authors: Manocha Nilanshu , Kumar Prashant , Khanna Madhu 
Published: January 2024

AbstractThe dengue outbreak is one of the serious global public health concerns. The World Health Organization reported 3,80,171 cases and 113 deaths this year till March 2023, and the rate of infection is expected to increase in vulnerable parts of the world. The development of vaccines is the best approach to managing infectious diseases. All the approved vaccines against dengue are based on live-attenuated virus but they have been questioned for their effectiveness in some population categories. Additionally, random occurrence of four closely related serotypes of dengue virus in humans leading to antibody-dependent enhancement of the disease is yet another cause of vaccine ineffectiveness. Therefore, development of a therapeutic subunit-vaccine based on epitopes from all four serotypes may be expected to provide effective cross-protective cellular immunity. Towards this end, we designed a multi-epitope chimeric immunogen using envelop protein of dengue virus. The MHC-I binding T-cell epitopes were predicted based on their immunogenicity, allergenicity and antigenicity. NetMHCpan-EL4.1 prediction method was used to determine the binding ability of the epitopes with HLA alleles with population coverage of over 99%. The five most potent epitopes based on their immunogenicity, population coverage and prediction scores were selected for each serotype and a multi-epitope polypeptide was generated by merging peptides with AAY linker. The polypeptide was predicted to be an antigen and a non-allergen with a stable tertiary structure retaining a half-life of 4.4 hours in mammalian system. The polypeptide has the potential to elicit effective cellular immune response against all the dengue virus serotypes.
When the pen is mightier than the sword: semi-automatic 2 and 3D image labelling
Authors: Hollandi Réka , Bauer David , Diosdi Akos , Schrettner Bálint , Toth Timea , Hirling Dominik , Hollandi Gábor , Harmati Maria , Molnár József , Horvath Peter 
Published: January 2024

AbstractData is the driving engine of learning-based algorithms, the creation of which fundamentally determines the performance, accuracy, generalizability and quality of any model or method trained on it. When only skilled or trained personnel can create reliable annotations, assisted software solutions are desirable to reduce the time and effort the expert must spend on labelling. Herein is proposed an automated annotation helper software package in napari that offers multiple methods to assist the annotator in creating object-based labels on 2D or 3D images.
Origin and evolutionary trajectories of brown algal sex chromosomes
Authors: Barrera-Redondo Josué , Lipinska Agnieszka P. , Liu Pengfei , Dinatale Erica , Cossard Guillaume , Bogaert Kenny , Hoshino Masakazu , Craig Rory J. , Avia Komlan , Leiria Goncalo , Avdievich Elena , Liesner Daniel , Luthringer Rémy , Godfroy Olivier , Heesch Svenja , Nehr Zofia , Brillet-Guéguen Loraine , Peters Akira F. , Hoarau Galice , Pearson Gareth , Aury Jean-Marc , Wincker Patrick , Denoeud France , Cock J Mark , Haas Fabian B. , Coelho Susana M 
Published: January 2024

ABSTRACTSex chromosomes fall into three classes: XX/XY, ZW/ZZ and U/V systems. The rise, evolution and demise of U/V systems has remained an evolutionary enigma. Here, we analyse genomes spanning the entire brown algal phylogeny to decipher their sex-determination evolutionary history. U/V sex chromosomes emerged between 450 and 224 million years ago, when a region containing the pivotal male-determinantMINlocated in a discrete region in proto-U and proto-V chromosomes ceased recombining. Over time, nested inversions led to step-wise expansions of the sex locus, accompanying increasing morphological complexity and sexual differentiation of brown seaweeds. Unlike XX/XY and ZW/ZZ, brown algal U/V evolve mainly by gene gain, showing minimal degeneration. They are structurally dynamic and act as genomic ‘cradles’ fostering the birth of new genes, potentially from ancestrally non coding sequences. Our analyses demonstrate that hermaphroditism arose from ancestral males that acquired U-specific genes by ectopic recombination, and that in the transition from a U/V to an XX/XY system, V-specific genes moved down the genetic hierarchy of sex determination. Both events lead to the demise of U and V and erosion of their specific genomic characteristics. Taken together, our findings offer a comprehensive model of U/V sex chromosome evolution.
Host brain environmental influences on transplanted medial ganglionic eminence progenitors
Authors: Paterno Rosalia , Vu Thy , Hsieh Caroline , Baraban Scott C. 
Published: January 2024

AbstractInterneuron progenitor transplantation can ameliorate disease symptoms in a variety of neurological disorders. This strategy is based on transplantation of embryonic medial ganglionic eminence (MGE) progenitors. Elucidating host brain environment influences on interneuron progenitors as they integrate is critical to optimizing this strategy across different disease states. Here, we systematically evaluated age and brain region influences on survival, migration and differentiation of transplant-derived cells. We find that early postnatal MGE transplantation yields superior survival and more extensive migratory capabilities compared to juvenile or adult. MGE progenitors migrate more widely in cortex compared to hippocampus. Maturation to interneuron subtypes is regulated by age and brain region. MGE progenitors transplanted into dentate gyrus sub-region of early postnatal hippocampus can differentiate into astrocytes. Our results suggest that host brain environment critically regulates survival, spatial distribution and maturation of MGE-derived interneurons following transplantation. These findings inform and enable optimal conditions for interneuron transplant therapies.
The preoptic Kisspeptin/nNOS/GnRH (KiNG) neuronal network regulates rhythmic LH release through a dual activation-inhibition mechanism
Authors: Delli Virginia , Seux Charles-Antoine , Dehame Julien , Nair Sooraj , Lhomme Tori , Chachlaki Konstantina 
Published: January 2024

AbstractGonadotropin-releasing hormone (GnRH) neurons are the final common target of a complex network of cells cooperating for the central control of reproduction. The balance between excitatory and inhibitory transsynaptic and non-synaptic inputs is crucial for the maintenance of the GnRH rhythms: the pulse and the surge. The precise mechanisms behind this remain under debate. In this work, we challenge the hypothesis that excitatory and inhibitory inputs from kisspeptin and neuronal nitric oxide (NO) synthase (nNOS)-expressing neurons orchestrates GnRH release, in a microcircuit that we call the Kisspeptin/nNOS/GnRH (KiNG) neuronal network. Our work specifically focuses on the role of nNOS neurons located in the organum vasculosum laminae terminalis (OV) and the median preoptic nucleus (MePO). nNOS and kisspeptin neurons interact anatomically and functionally, with the kisspeptin receptor (Kiss1r) being differentially regulated in nNOS-expressing neurons across the female estrous cycle. Using a novel viral tool allowing for the measurement of NO/cGMP levels with exquisite sensitivity, we demonstrate that kisspeptin is able to induce NO-dependent cGMP production in the OV/MePO, including in GnRH neuronsin vivo. Using electrophysiological, genetic, chemogenetic and pharmacologic approaches, we reveal that NO production from nNOS neurons in the OV/MePO is needed to fine-tune the GnRH/LH response to kisspeptin, and specifically to turn off GnRH release, thus generating pulses. Our findings provide valuable insights into the tripartite KiNG neuronal network governing the regulation of the GnRH/LH pulse and surge.
Applying gradient tree boosting to QTL mapping with Shapley additive explanations
Authors: Ishibashi Tomohiro , Onogi Akio 
Published: January 2024

AbstractMapping quantitative trait loci (QTLs) is one of the major goals of quantitative genetics; however, identifying the interactions between QTLs (i.e., epistasis) remains challenging. Recently developed machine learning methods, such as deep learning and gradient boosting, are transforming the real world. These methods could advance QTL mapping methodologies because of their high capability for capturing complex relationships among features. One problem with applying such complex models to QTL mapping is evaluation of feature importance. In this study, XGBoost, a popular gradient tree boosting algorithm, was applied for QTL mapping in biparental populations with Shapley additive explanations (SHAPs). SHAP is a local (i.e., instance-wise) importance index with the desired properties as feature importance indices. The SHAP-assisted XGBoost (SHAP-XGB) was compared with conventional methods, including composite interval mapping (CIM), multiple interval mapping (MIM), inclusive CIM (ICIM), and BayesC, using simulations and rice heading date data. SHAP-XGB performed comparable to CIM, MIM, ICIM, and BayesC in mapping main QTL effects and was superior to MIM, ICIM, and BayesC in mapping QTL interaction effects. As SHAP can evaluate local importance, interactions between markers can be visualized by plotting SHAP interaction values for each instance (plant/line). These results illustrated the strength of SHAP-XGB in detecting and interpreting epistatic QTLs and suggest the possibility that SHAP-XGB complements conventional methods.
Development and characterization of phospho-ubiquitin antibodies to monitor PINK1-PRKN signaling in cells and tissue
Authors: Watzlawik Jens O. , Hou Xu , Richardson Tyrique , Lewicki Szymon L. , Siuda Joanna , Wszolek Zbigniew K. , Cook Casey N. , Petrucelli Leonard , DeTure Michael , Dickson Dennis W. , Antico Odetta , Muqit Miratul M. K. , Fishman Jordan B. , Pirani Karima , Kumaran Ravindran , Polinski Nicole K. , Fiesel Fabienne C. , Springer Wolfdieter 
Published: January 2024

ABSTRACTThe selective removal of dysfunctional mitochondria, a process termed mitophagy, is critical for cellular health and impairments have been linked to aging, Parkinson disease, and other neurodegenerative conditions. A central mitophagy pathway is orchestrated by the ubiquitin (Ub) kinase PINK1 together with the E3 Ub ligase PRKN/Parkin. The decoration of damaged mitochondrial domains with phosphorylated Ub (p-S65-Ub) mediates their elimination though the autophagy system. As such p-S65-Ub has emerged as a highly specific and quantitative marker of mitochondrial damage with significant disease relevance. Existing p-S65-Ub antibodies have been successfully employed as research tools in a range of applications including western blot, immunocytochemistry, immunohistochemistry, and ELISA. However, physiological levels of p-S65-Ub in the absence of exogenous stress are very low, therefore difficult to detect and require reliable and ultrasensitive methods. Here we generated and characterized a collection of novel recombinant, rabbit monoclonal p-S65-Ub antibodies with high specificity and affinity in certain applications that allow the field to better understand the molecular mechanisms and disease relevance of PINK1-PRKN signaling. These antibodies may also serve as novel diagnostic or prognostic tools to monitor mitochondrial damage in various clinical and pathological specimens.
Decline of honeybees and its consequences for beekeepers and crop pollination in western Nepal
Authors: Kortsch S. , Timberlake T.P. , Cirtwill A.R. , Sapkota S. , Rokaya M. , Devkota K. , Roslin T. , Memmott J. , Saville N. 
Published: January 2024

AbstractPollination service by insects is globally threatened, yet trends outside of Europe and North America are poorly understood. Therefore, in less-studied regions of the world, beekeeper records can provide valuable insights into changes in pollinator populations.We conducted a questionnaire survey of 116 beekeepers in 10 villages in the Jumla District of western Nepal, where the native honeybeeApis cerana ceranais widely kept as a managed honeybee. We complemented the beekeeper survey with field data on insect-crop visitation, a household income survey, and an interview with a local lead beekeeper.76% of beekeepers reported declines in theApis cerana ceranapopulation. 86% experienced declines in honey yield per hive, and 78% reported declines in the number of beehives per beekeeper. Honey yield per hive fell by 50% between 2012 and 2022, whilst the number of occupied hives decreased by 44%. Beekeepers ranked climate change and declining flower abundance as the most-important drivers of the decline.The drastic bee declines raise concerns for the future food and economic security of this region, where honey sales contribute to 16% of total household farming income.Apis cerana ceranaplays a major role in crop pollination and contributes more than 50% of all flower visits to apple, cucumber, and pumpkin.To mitigate further declines in this region, we promote the use of pollinator-friendly farming practices including more wild flowers and maintenance of native habitat areas, and well-insulated log or top-bar log hives to buffer bees against extreme temperature fluctuations, which are expected to worsen with climate warming.
Astrocytic CREB in nucleus accumbens promotes susceptibility to chronic stress
Authors: Holt Leanne M. , Gyles Trevonn M , Parise Eric M. , Minier-Toribio Angelica , Markovic Tamara , Rivera Matthew , Yeh Szu-Ying , Nestler Eric J. 
Published: January 2024

AbstractBackgroundIncreasing evidence implicates astrocytes in stress and depression in both rodent models and human Major Depressive Disorder (MDD). Despite this, little is known about the transcriptional responses to stress of astrocytes within the nucleus accumbens (NAc), a key brain reward region, and their influence on behavioral outcomes.MethodsWe used whole cell sorting, RNA-sequencing, and bioinformatic analyses to investigate the NAc astrocyte transcriptome in male mice in response to chronic social defeat stress (CSDS). Immunohistochemistry was used to determine stress-induced changes in astrocytic CREB within the NAc. Finally, astrocytic regulation of depression-like behavior was investigated using viral-mediated manipulation of CREB in combination with CSDS.ResultsWe found a robust transcriptional response in NAc astrocytes to CSDS in stressed mice, with changes seen in both stress-susceptible and stress-resilient animals. Bioinformatic analysis revealed CREB, a transcription factor widely studied in neurons, as one of the top-predicted upstream regulators of the NAc astrocyte transcriptome, with opposite activation states seen in resilient versus susceptible mice. This bioinformatic result was confirmed at the protein level with immunohistochemistry. Viral overexpression of CREB selectively in NAc astrocytes promoted susceptibility to chronic stress.ConclusionsTogether, our data demonstrate that the astrocyte transcriptome responds robustly to CSDS and, for the first time, that transcriptional regulation in astrocytes contributes to depressive-like behaviors. A better understanding of transcriptional regulation in astrocytes may reveal unknown molecular mechanisms underlying neuropsychiatric disorders.
AnnoView enables large-scale analysis, comparison, and visualization of microbial gene neighborhoods
Authors: Wei Xin , Tan Huagang , Lobb Briallen , Zhen William , Wu Zijing , Parks Donovan H. , Neufeld Josh D. , Moreno-Hagelsieb Gabriel , Doxey Andrew C. 
Published: January 2024

AbstractThe analysis and comparison of gene neighborhoods is a powerful approach for exploring microbial genome structure, function, and evolution. Although numerous tools exist for genome visualization and comparison, genome exploration across large genomic databases or user-generated datasets remains a challenge. Here, we introduce AnnoView, a web server designed for interactive exploration of gene neighborhoods across the bacterial and archaeal tree of life. Our server offers users the ability to identify, compare, and visualize gene neighborhoods of interest from 30,238 bacterial genomes and 1,672 archaeal genomes, through integration with the comprehensive GTDB and AnnoTree databases. Identified gene neighborhoods can be visualized using pre-computed functional annotations from different sources such as KEGG, Pfam, and TIGRFAM, or clustered based on similarity. Alternatively, users can upload and explore their own custom genomic datasets in GBK, GFF, or CSV format, or use AnnoView as a genome browser for relatively small genomes (e.g., viruses and plasmids). Ultimately, we anticipate that AnnoView will catalyze biological discovery by enabling user-friendly search, comparison, and visualization of genomic data. AnnoView is available athttp://annoview.uwaterloo.ca