bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuro-oncological superiority of supratotal resection in lower-grade gliomas
Authors: Gallotti Alberto L , Rossi Marco , Conti Nibali Marco , Sciortino Tommaso , Gay Lorenzo G , Puglisi Guglielmo , Leonetti Antonella , Bruno Francesco , Rudà Roberta , Soffietti Riccardo , Cerri Gabriella , Bello Lorenzo
Published: December 2024

Background

Supratotal-resection (SpTR) is a promising surgical strategy in lower-grade gliomas (LGGs). SpTR assessment, feasibility and distinctive features, as well as clinical benefit at first and second surgery and on overall survival must be better characterized. The critical percentage of resection exceeding FLAIR margins to obtain clinical benefit and its impact on long-term functional performance are also undefined.

Methods

Included were 704 patients with primary and 439 with recurrent LGGs seen between 2010 and 2019, who underwent resection with brain-mapping technique (BMT) aimed at achieving a SpTR without any “a-priori” selection. Extent-of-resection, evaluated on 3D-FLAIR-MR and categorized according to residual tumor and cavity volume, was associated with progression-free survival (PFS) and malignant(M)PFS at first and second surgery and overall survival by univariate, multivariate, and propensity-score analysis. Functional performance was assessed by neuropsychological (NPS) evaluation.

Results

SpTR evaluation requires volumetric assessment enhanced by brain deformation measurement in parietal tumors; SpTR rate accounts on average for 50.2% and 35.7% at first and second surgery is higher in grade-2, frontal, and temporal locations (at expenses of total resection [TR]). Compared to TR, SpTR reduces and postpones first and second recurrences in all molecular subtypes and grades, delays MPFS without difference in rate, and prolongs overall survival (OS). A degree of SpTR > 120% associates with the lowest recurrence risk. SpTR associates with the best NPS longitudinal course.

Conclusions

This study supports the feasibility of SpTR in LGGs, its benefit at first and second surgery regardless of molecular subtypes, and on OS, significantly reducing recurrence when SpTR > 120%; SpTR also associates with the best patients’ functional outcome.
A versatile reactive layer toward ultra-long lifespan lithium metal anodes
Authors: Wu Jinlun , Lu Yuheng , Ke Xianlan , Zheng Linying , Liao Rongfeng , Wu Dingcai
Published: December 2024

Unstable anode/electrolyte interfaces have significantly hindered the development of lithium (Li) metal batteries under high rates and large capacities. In this study, a versatile reactive layer based on sulfur-selenium crosslinked polyacrylonitrile brushes has been developed by a combined strategy of polymer topology design and chemical crosslinking. The sulfur-selenium crosslinked polyacrylonitrile side-chains can react with Li to generate passivated Li2S-Li2Se-containing solid electrolyte interphase while 3D lithiophilic porous nanonetworks enable Li penetration, contributing to achieving rapid and uniform Li ion flux and a dendrite-free anode. With these merits, ultralong-term stable cycling (over 1 year and 4 months) at a high current density of 10 mA cm−2 has been achieved for the protected Li anodes. Moreover, even when tested in high-loading Li|NCM622 cell (21.6 mg cm−2) and Li-S cell with a low negative to positive electrode capacity ratio (1.4), stable cycling performances can also be achieved.
A 3D braincase of the early jawed vertebrate Palaeospondylus from Australia
Authors: Burrow Carole J , Young Gavin C , Lu Jing
Published: December 2024

Palaeospondylus gunni Traquair, 1890, is represented by thousands of similarly preserved articulated fossils from the Achannaras quarry (∼390 Mya) in Caithness, Scotland. With radically different interpretations of its structure, it has been assigned to almost all major jawless and jawed vertebrate groups. Here we report a new and older species of Palaeospondylus from the Early Devonian of Australia (c. 400 Ma), investigated using high-resolution computed tomography. Its 3D-preserved braincase demonstrates a combination of primitive gnathostome features including an anteriorly positioned transverse cranial fissure of uncertain homology, a large dorsal fontanelle and a small hypophysial fossa. Contrary to recent interpretations of P. gunni, the new braincase shows that Palaeospondylus lacks both a postorbital process and an intracranial joint. Our new Australian species extends the history of Palaeospondylus back some 10 million years prior to its occurrence in Scotland. The newly identified neurocranial characters have been coded into a phylogenetic analysis that places Palaeospondylus as a sister group of the Chondrichthyes, but some neurocranial characters could indicate a phylogenetic position within the gnathostome stem group.
Prevalence of Tobacco and Poly-Tobacco Use as a Function of Sexual Orientation Identity and Sex
Authors: Deyo Alexa G , LaRowe Lisa R , Powers Jessica M , Ruiz Raymond A , Kidwell Katherine M , Ditre Joseph W
Published: December 2024

Introduction

Limited research has characterized poly-tobacco use (ie, use of at least two nicotine/tobacco products) among adults with sexual minoritized (SM) identities (ie, lesbian, gay, and bisexual). Additional work is needed to examine disparities in use by sexual orientation identity and determine whether these disparities differ by sex. We aimed to examine the prevalence of tobacco product use and poly-tobacco use by sexual orientation identity and sex among a nationally representative sample of US adults.

Aims and Methods

Data were drawn from 32 352 adult respondents (34.9% 18–24 years; 10.4% SM; 51.4% female) at Wave 5 (2018–2019) of the Population Assessment of Tobacco and Health (PATH) Study. Logistic regression models tested main and interactive effects of sexual orientation identity and sex on tobacco product use and poly-tobacco use.

Results

SM (vs. heterosexual) participants were more likely to report the use of cigarettes, e-cigarettes, hookah, filtered cigars, and cigarillos (ORs = 1.71–3.27) and poly-tobacco use (OR = 1.83). Male (vs. female) participants, regardless of sexual orientation identity, were more likely to report use of each tobacco product (ORs = 1.30–28.73) and poly-tobacco use (OR = 1.73). Significant interactions revealed stronger associations between sexual orientation identity and cigarette and e-cigarette use among SM females (vs. heterosexual females) and SM males (vs. heterosexual males; aORs = 1.42–4.10). Tobacco use further varied within SM and heterosexual groups based on sex.

Conclusions

This study contributes to a growing literature demonstrating disparities in tobacco use among SM individuals. Findings underscore the need for comprehensive assessment of associations between sexual orientation identity and sex in tobacco use treatment.

Implications

This study examines the intersection of sexual orientation identity, sex, and tobacco use among a nationally representative sample of US adults. Findings highlight tobacco-related disparities among sexual minoritized individuals and underscore the importance of routine monitoring and intervening to reduce the disproportionate prevalence of tobacco use among this population.
Effects of E-Cigarette Warning Labels About Mental Health Consequences of Nicotine Addiction Among Young Adults in the USA: Results From a Randomized Controlled Experiment
Authors: Marynak Kristy L , Cohen Joanna E , Thrul Johannes , Kennedy Ryan D , Limaye Rupali , Moran Meghan B
Published: December 2024

Introduction

Since 2016, the US Food and Drug Administration (FDA) has required e-cigarette packaging and advertising to bear the warning: “WARNING: THIS PRODUCT CONTAINS NICOTINE. NICOTINE IS AN ADDICTIVE CHEMICAL.” Nicotine has numerous adverse consequences besides addiction, including increased anxiety and depression symptoms that arise from nicotine withdrawal. We tested the effects of exposure to text-only e-cigarette package labels about the psychological consequences of nicotine withdrawal.

Aims and Methods

We randomized 1919 US young adults aged 18–24 years to view one of four warning label conditions: a no-message control, the current FDA warning, a message that “nicotine addiction can worsen depression and anxiety symptoms,” and a message that “nicotine addiction is a source of stress.” We explored associations between condition and intentions to use or quit e-cigarettes and perceived message effectiveness.

Results

Label condition was not associated with intentions to use or quit e-cigarettes. Intentions were equivalent among those who viewed the FDA label and those who viewed the no-message control. Compared with the FDA label, the depression/anxiety label and the stress label produced greater agreement among participants that the message “makes me concerned about nicotine addiction” after adjustment for sociodemographic characteristics; those who viewed the depression/anxiety label had greater agreement that the message “discourages me from wanting to use nicotine.”

Conclusions

While brief exposure to the warnings tested may not impact young adults’ intentions to use or quit vaping, messages about stress, depression, and anxiety arising from nicotine addiction had higher perceived effectiveness among young adults than the FDA’s current message about addictiveness.

Implications

Findings from this randomized controlled experiment among US young adults suggest that warnings about the mental health consequences of nicotine addiction might be one type of message to consider including in a suite of required e-cigarette warnings and as part of a comprehensive effort to educate the public about the risks of commercial tobacco products.
Rooting for survival: how plants tackle a challenging environment through a diversity of root forms and functions
Authors: Ramachandran Prashanth , Ramirez Andrea , Dinneny José R
Published: December 2024

The current climate crisis has global impacts and will affect the physiology of plants across every continent. Ensuring resilience of our agricultural and natural ecosystems to the environmental stresses imposed by climate change will require molecular insight into the adaptations employed by a diverse array of plants. However, most current studies continue to focus on a limited set of model species or crops. Root systems are particularly understudied even though their functions in water and nutrient uptake are likely pivotal for plant stress resilience and sustainable agriculture. In this review, we highlight anatomical adaptations in roots that enable plant survival in different ecological niches. We then present the current state of knowledge for the molecular underpinnings of these adaptations. Finally, we identify areas where future research using a biodiversity approach can fill knowledge gaps necessary for the development of climate-resilient crops of the future.
Volatile content and genetic variation of citron in Tibet and Yunnan
Authors: Feng Di , Liu Shengjun , Chen Mengjun , Wang Shaohua , Xu Miao , Liu Chenglang , Huang Wenkai , Wang Ming , Xie Pu , Chai Lijun , Ye Junli , Xu Qiang , Zeng Xiuli , Xu Juan , Deng Xiuxin
Published: December 2024

Citron (Citrus medica) is a representative aromatic species of the Citrus genus in the Rutaceae family. To determine the volatile profiles and genetic variation of citron, we collected 218 citron accessions within China, including 130 from Yunnan and 88 from Tibet. We identified a total of 80 volatile compounds from their pericarps. Among the volatile profiles, monoterpenes were identified as the predominant compounds, with d-limonene being the most abundant. The correlation analysis indicated that the content of 5 volatile compounds was significantly associated with the proportion of juice vesicles in citron fruits. Citrons from Tibet exhibited a higher total volatile content and lower variability in their volatile profile than those from Yunnan. Comparative analysis revealed significant differences in the levels of 48 volatile compounds between Tibetan and Yunnan citrons. Furthermore, we assembled a 402.23-Mb chromosome-scale citron genome (contig N50 = 37.51 Mb) and resequenced 105 representative citron accessions. The population structure analysis divided these citron accessions into two populations: Yunnan and Tibet. The nucleotide diversity in the Tibet population was significantly lower than that in the Yunnan population on a genome-wide scale. Based on d-limonene content, we identified JUNGBRUNNEN1-like (CmJUB1-like), a NAC transcription factor, (−) on chromosome 7 through a genome-wide association study. Overexpressing CmJUB1-like significantly enhanced d-limonene and total monoterpene levels in citron. These results broaden our understanding of the genetic mechanisms influencing volatile profiles and may facilitate the molecular breeding of citrus.
Towards rational control of seed oil composition: dissecting cellular organization and flux control of lipid metabolism
Authors: Bates Philip D , Shockey Jay
Published: December 2024

Plant lipids represent a fascinating field of scientific study, in part due to a stark dichotomy in the limited fatty acid (FA) composition of cellular membrane lipids vs the huge diversity of FAs that can accumulate in triacylglycerols (TAGs), the main component of seed storage oils. With few exceptions, the strict chemical, structural, and biophysical roles imposed on membrane lipids since the dawn of life have constrained their FA composition to predominantly lengths of 16–18 carbons and containing 0–3 methylene-interrupted carbon-carbon double bonds in cis-configuration. However, over 450 “unusual” FA structures can be found in seed oils of different plants, and we are just beginning to understand the metabolic mechanisms required to produce and maintain this dichotomy. Here we review the current state of plant lipid research, specifically addressing the knowledge gaps in membrane and storage lipid synthesis from 3 angles: pathway fluxes including newly discovered TAG remodeling, key acyltransferase substrate selectivities, and the possible roles of “metabolons.”
Corporate Loan Spreads and Economic Activity
Authors: Saunders Anthony , Spina Alessandro , Steffen Sascha , Streitz Daniel
Published: December 2024

We investigate the predictive power of loan spreads for forecasting business cycles, specifically focusing on more constrained, intermediary-reliant firms. We introduce a novel loan-market-based credit spread constructed using secondary corporate loan-market prices over the 1999 to 2023 period. Loan spreads significantly enhance the prediction of macroeconomic outcomes, outperforming other credit-spread indicators. We also explore the underlying mechanisms and differentiate between borrower fundamentals and financial frictions. Evidence suggests that supply-side frictions are a decisive factor in the forecasting ability of loan spreads.
Association of lupus low disease activity state and remission with reduced organ damage and flare in systemic lupus erythematosus patients with high disease activity: a multi-national, longitudinal cohort study
Authors: Kandane-Rathnayake Rangi , Golder Vera , Louthrenoo Worawit , Chen Yi-Hsing , Cho Jiacai , Lateef Aisha , Hamijoyo Laniyati , Luo Shue-Fen , Wu Yeong-Jian J , Navarra Sandra V , Zamora Leonid , Li Zhanguo , Sockalingam Sargunan , Katsumata Yasuhiro , Harigai Masayoshi , Hao Yanjie , Zhang Zhuoli , Basnayake B M D B , Chan Madelynn , Kikuchi Jun , Takeuchi Tsutomu , Bae Sang-Cheol , Oon Sheeran , O’Neill Sean , Goldblatt Fiona , Ng Kristine (Pek Ling) , Law Annie , Tugnet Nicola , Kumar Sunil , Tee Cherica , Tee Michael , Ohkubo Naoaki , Tanaka Yoshiya , Lau Chak Sing , Nikpour Mandana , Morand Eric F , Hoi Alberta
Published: December 2024

Objective

High disease activity status (HDAS) in patients with systemic lupus erythematosus (SLE) is associated with adverse long-term outcomes. We examined the frequency of lupus low disease activity state (LLDAS) and remission (REM) attainment in HDAS patients and whether their attainment was associated with improved patient outcomes.

Methods

Demographic, clinical and outcomes data, collected prospectively from a multinational cohort between 2013 and 2020, were analysed. Disease activity was assessed using SLEDAI-2K. HDAS was defined as SLEDAI-2K ≥ 10. Patients’ first visit with SLEDAI-2K ≥ 10 was assigned as baseline. Survival analyses were performed to examine the associations between cumulative and sustained LLDAS and REM attainment in HDAS patients and subsequent organ damage accrual and flare.

Results

A total of 1029 HDAS patients with a median study duration of 2.7 years [IQR: 1.0, 4.8] were studied. LLDAS and REM were attained at least once by 71% (LLDAS-ever, n = 726) and 41% (REM-ever, n = 418) of patients. Approximately one-fifth of patients attained ≥50% cumulative time in LLDAS or REM. In total, 37% (n = 385) of patients attained ≥3months of sustained LLDAS, with progressively lower proportions of patients attaining longer periods of sustained LLDAS. Lower proportions of patients attained sustained REM. Attainment of cumulative and sustained LLDAS or REM provided significant protection against damage accrual and flare in HDAS patients. Sustained periods of LLDAS and REM were difficult to achieve and were therefore a more stringent target, but provided the most protection against damage accrual or flare.

Conclusion

LLDAS and REM were achievable targets in HDAS patients, and provided significant protection against adverse outcomes.
Risk factors of COVID-19 related hospitalization of paediatric patients with rheumatic diseases: a systematic review and meta-analysis
Authors: Zhao Qianzi , Wallace Beth , Ronis Tova , Jung Lawrence
Published: December 2024

Objective

Among adults who develop coronavirus disease 2019 (COVID-19), those with rheumatic diseases (RDs) have similar hospitalization rates compared with those without RDs. Similar comparisons are lacking in children, due to the overall rarity of COVID-19-related hospitalization in this population. We aimed to examine the risk factors for COVID-19-related hospitalization in paediatric patients with RDs.

Methods

We conducted a systemic literature search in MEDLINE, EMBASE, Web of Science and China National Knowledge Infrastructure from 1 December 2019, through 22 January 2024. We included observational studies based on inclusion and exclusion criteria. Odds ratios (ORs) with 95% CI were calculated.

Results

Eight cohort studies capturing 1501 paediatric RD patients with SARS-CoV-2 and 118 COVID-19-related hospitalization were included. Odds of hospitalization was increased in children with RDs compared with healthy children. While the diagnosis of juvenile idiopathic arthritis (JIA) was associated with reduced odds of hospitalization overall (OR 0.43 [95% CI: 0.27, 0.68]), systemic JIA was associated with increased odds of hospitalization (OR 2.54 [95% CI: 1.01, 6.40]). The use of glucocorticoids (OR 5.36 [95% CI: 2.21, 13.04]), rituximab (OR 4.62 [95% CI: 1.87, 11.40]), mycophenolate mofetil (OR 4.17 [95% CI: 1.08, 16.16]), hydroxychloroquine (OR 2.97 [95% CI: 1.42, 6.21]), and IL-1 inhibitors (OR 2.28 [95% CI: 1.09, 4.78]) was associated with increased odds of hospitalization, while the use of TNFα inhibitors was associated with reduced odds (OR 0.35 [95% CI: 0.20, 0.66]).

Conclusion

Children with RDs are at risk of severe COVID-19 outcomes, while children with JIA taking TNFα inhibitors might be at a lower risk.
Pink-pigmented variant of Clavibacter michiganensis expands phenotypic range of tomato bacterial canker pathogen
Authors: Haghverdi Malihe , Taghavi S. Mohsen , Zarei Sadegh , Mafakheri Hamzeh , Abachi Hamid , Briand Martial , Taghouti Geraldine , Portier Perrine , Jacques Marie-Agnes , Osdaghi Ebrahim
Published: December 2024

Bacterial canker of tomato caused by the Gram-positive corynebacterial species Clavibacter michiganensis is one of the most destructive seed-borne diseases in both open air and greenhouse tomatoes. The pathogen is a regulated agent in all tomato-producing countries as translocation of infected tomato materials transports the bacterium into new areas. Clavibacter michiganensis is generally known to have yellow-pigmented colonies on culture media, which is a key differentiative phenotypic feature in standard diagnostic guidelines. During 2020 and 2021, pink-pigmented corynebacterial strains were isolated from tomato seeds (cv. Sun 6189F1) and plants showing severe canker symptoms in Southern Iran. The six pink-pigmented strains were pathogenic on tomato and pepper seedlings under greenhouse conditions, and gave positive results with C. michiganensis-specific primers pairs described in the literature. Phylogenomics and DNA similarity calculations showed that the pink-pigmented strains were highly similar to the authentic yellow-pigmented members of the pathogen. Thus, they were identified as a new phenotypic variant of tomato bacterial canker pathogen. Whole genome screenings accomplished with PCR-based assays showed that the pink strains contain all pathogenicity determinant genes described in C. michiganensis. Further, orthologous gene clusters in the pink-pigmented strains were more similar to the pathogenic members of C. michiganensis than to those of non-pathogenic tomato-associated Clavibacter species. Results obtained in this study demonstrate the emergence of a new pink-pigmented variant of C. michiganensis and highlight the importance of colony pigmentation/morphology in culture-based detection of the bacterium. The need for updating diagnostic guidelines on the colony variants of the pathogen is further discussed.
Corneal Endothelial Cell Morphology in Eyes With Down Syndrome
Authors: Okubo Hiroshi , Sotozono Chie , Kinoshita Shigeru
Published: December 2024

Purpose:

To explore the morphological characteristics of corneal endothelial cells in eyes with Down syndrome.

Methods:

We conducted a comparative analysis of corneal endothelial cell density, coefficient of variation, hexagonal cell appearance rate, and corneal thickness using specular microscopy. Our study included 21 eyes of 11 patients with Down syndrome and 37 eyes of 19 control subjects.

Results:

In all eyes with Down syndrome, corneal endothelial cell density exceeded 2000 cells/mm2, and no abnormalities in cell morphology or significant differences from the control group were observed across all parameters.

Conclusions:

The structure and function of corneal endothelial cells in eyes with Down syndrome were within the normal range, even in the presence of chromosomal abnormalities of 21-trisomy in somatic cells.
Linear Scleroderma En Coup de Sabre: A Case Series With Eyelid Involvement and Management
Authors: Kok Li Teng , Malik Mohsan , Fayers Tessa , Sorkou Konstantina , Issa Alia , Ezra Daniel G.
Published: December 2024

Linear scleroderma en coup de sabre is a rare subtype of localized scleroderma. It is typically characterized by linear sclerosis and atrophy of the skin and underlying dermis affecting the frontoparietal region above the brow. The linear sclerotic lesions rarely extend into the upper eyelid. In this case series, the authors describe the presentation of 3 en coup de sabre cases, in particular the associated eyelid and adnexal findings which include upper eyelid skin fibrosis, sulcus hollowing, and eyelid retraction. The authors also describe the range of reconstructive treatment options in the remission phase with a combination of autologous fat transfer, injectable filler, eyelid retraction repair, and contralateral ptosis repair to improve facial symmetry and cosmesis of en coup de sabre lesions on the forehead, brow and eyelid region.
Multi-omic characterization of human sural nerves across polyneuropathies
Authors: Heming Michael , Wolbert Jolien , Börsch Anna-Lena , Thomas Christian , Mausberg Anne K. , Lu I-Na , Tietz Julia , Dienhart Finja , Dambietz Christine , Uerschels Anne-Kathrin , Keyvani Kathy , Szepanowski Fabian , Eggert Bianca , Liebig Kai C. , Doppler Kathrin , Üçeyler Nurcan , Aprea Julieta , Dahl Andreas , Stassart Ruth , Fledrich Robert , Wiendl Heinz , Sommer Claudia , Stettner Mark , Hörste Gerd Meyer zu
Published: December 2024

Diseases of peripheral nerves termed polyneuropathies (PNPs) are common, mechanistically heterogeneous, and challenging to diagnose. Here, we integrated single nuclei transcriptomics of peripheral nerves from 33 human PNP patients and four controls (365,708 nuclei) with subcellular spatial transcriptomics. We identified novel and human-specific nerve cell type markers including unexpectedly heterogeneous perineurial fibroblasts. All PNPs shared a loss of myelinating and an increase in repair Schwann cells and endoneurial lipid-associated macrophages. Transcriptional changes affected multiple cells outside of the endoneurium across PNPs, suggesting PNPs as ‘pan-nerve diseases’. Spatially, PNPs showed a previously unknown perineurial hyperplasia and fibrotic dispersion and this was most pronounced in immune-mediated PNPs. Single cell transcriptomics supported the differential diagnosis of PNPs with potential for future unbiased diagnostic classification.

One-sentence summary

The first large-scale integrated single cell and spatial transcriptomic characterization of human peripheral nerves identifies novel cell markers and unexpected heterogeneity of perineurial cells, reveals polyneuropathies as ‘pan-nerve diseases’, and shows that single cell transcriptomics hold potential for unbiased nerve disease classification.
FastReseg: using transcript locations to refine image-based cell segmentation results in spatial transcriptomics
Authors: Wu Lidan , Beechem Joseph M. , Danaher Patrick
Published: December 2024

Spatial transcriptomics (ST) is a rapidly advancing field, yet it is challenged by persistent issues with cell segmentation accuracy, which can bias biological interpretations by making cells appear more similar to their neighbors than they truly are. FastReseg introduces a novel class of algorithm that employs transcriptomic data not to redefine cell boundaries but to rectify inaccuracies within existing image-based segmentation outputs. By combining the rich information from image-based methods with the 3D precision of transcriptomic analysis, FastReseg enhances cell segmentation accuracy. A key innovation of FastReseg approach is its transcript scoring system, which scores each transcript for its goodness-of-fit within host cell using log-likelihood ratio. This scoring system facilitates the quick identification and correction of spatial doublets,i.e.cells erroneously segmented due to close proximity or spatial overlap in 2D. FastReseg approach offers several advantages: it reduces the risks of circularity in deriving cell boundaries from expression data and minimizes spatial-dependent biases arising from erroneous segmentation. It also addresses computational challenges often associated with existing transcript-based methods by introducing a heuristic, modular workflow that efficiently processes large datasets, a critical feature given the increasing size of spatial transcriptomics datasets. Its modular workflow allows for individual components to be optimized and seamlessly integrated back into the overall pipeline, accommodating ongoing advancements in segmentation technology. By enabling efficient management of large datasets and providing a scalable solution for refining cell segmentation, FastReseg is poised to enhance the quality and interpretability of spatial transcriptomics data even as underlying image-based cell segmentation techniques evolve.
In Search of Transcriptomic Correlates of Neuronal Firing-Rate Adaptation across Subtypes, Regions and Species: A Patch-seq Analysis
Authors: Meng John Hongyu , Kang Yijie , Lai Alan , Feyerabend Michael , Inoue Wataru , Martinez-Trujillo Julio , Rudy Bernardo , Wang Xiao-Jing
Published: December 2024

Can the transcriptomic profile of a neuron predict its physiological properties? Using a Patch-seq dataset of the primary visual cortex, we addressed this question by focusing on spike rate adaptation (SRA), a well-known phenomenon that depends on small conductance calcium (Ca)-dependent potassium (SK) channels. We first show that in parvalbumin-expressing (PV) and somatostatin-expressing (SST) interneurons (INs), expression levels of genes encoding the ion channels underlying action potential generation are correlated with the half-width (HW) of spikes. Surprisingly, the SK encoding gene is not correlated with the degree of SRA (dAdap). Instead, genes that encode proteins upstream from the SK current are correlated with dAdap, a finding validated by a different dataset from the mouse’s primary motor cortex that includes pyramidal cells and interneurons, as well as physiological datasets from multiple regions of macaque monkeys. Finally, we construct a minimal model to reproduce observed heterogeneity across cells, with testable predictions.
Gabapentin’s Effect on Human Dorsal Root Ganglia: Donor-Specific Electrophysiological and Transcriptomic Profiles
Authors: Demeter Jenna B. , Zurek Nesia A. , Koch Maddy R. , Goins Aleyah E. , Holguin Cristian O. , Shilling Mark W. , Ehsanian Reza , Alles Sascha R.A. , de la Peña June Bryan I.
Published: December 2024

Neuropathic pain affects approximately 10% of the adult population and is commonly treated with gabapentin (GBP), a repurposed anticonvulsant drug. Despite its widespread clinical use, GBP’s efficacy varies significantly among patients, highlighting the need to better understand its functional and molecular impacts on human pain-sensing neurons. In this study, we characterized the electrophysiological and transcriptomic effects of GBP on primary sensory neurons derived from the dorsal root ganglia (DRG) of ethically consented human donors. Using patch-clamp electrophysiology, we demonstrated that GBP treatment reduced neuronal excitability, with more pronounced effects in multi-firing vs. single-firing neuronal subtypes. Notably, significant donor-specific variability was observed in electrophysiological responsiveness to GBP treatmentin vitro. RNA sequencing of DRG tissue from the GBP-responsive donor revealed differences in the transcriptome-wide expression of genes associated with ion transport, synaptic transmission, inflammation, and immune response relative to non-responsive donors. Cross-transcriptomic analyses further showed that GBP treatment counteracted these altered processes, rescuing aberrant gene expression at the pathway level and for several key genes. This study provides a comprehensive electrophysiological and transcriptomic profile of the effects of GBP on human DRG neurons. These findings enhance our understanding of GBP’s mechanistic actions on peripheral sensory neurons and could help optimize its clinical use for neuropathic pain management.
An imbalance of naïve and effector T-cell phenotypes in early type 1 diabetes across conventional and regulatory subsets
Authors: Niederlova Veronika , Neuwirth Ales , Neuman Vit , Michalik Juraj , Charvatova Bela , Modrak Martin , Sumnik Zdenek , Stepanek Ondrej
Published: December 2024

Type 1 diabetes (T1D) is an autoimmune disease caused by the loss of self-tolerance toward insulin-producing pancreatic β-cells. Although the etiology of T1D is not fully understood, it is linked to dysregulation of the T-cell compartment. To identify T-cell signatures associated with T1D, we performed single-cell transcriptomic analysis of peripheral blood T-cells from newly diagnosed children, the same children after one year, and healthy donors. We observed reduced expression of genes related to effector and cytotoxic T-cell functions across conventional, unconventional, and regulatory T-cell subsets in diabetic children, particularly at the time of diagnosis. These findings were supported by flow cytometry analysis of the same cohort and by reanalysis of publicly available data. Overall, our results suggest that T1D is associated with impaired T-cell effector differentiation, which may contribute to immune dysregulation and loss of self-tolerance.
DiscoEPG: A Python package for characterization of insect electrical penetration graph (EPG) signals
Authors: Dinh Quang Dung , Kunk Daniel , Hy Truong Son , Vamsi Nalam , Dao Phuong D.
Published: December 2024

The Electrical Penetration Graph (EPG) technique is a well-known specialized tool that entomologists use to monitor and analyze the feeding behavior of piercing-sucking insects, such as aphids, whiteflies, and leafhoppers, on plants. Traditionally, the annotation is conducted by a well-trained technician who uses expert knowledge to compare the targeted waveforms with standard waveforms of aphid feeding behavior, which takes approximately 30 minutes to annotate an 8-hour recording depending on the complexity of the insect behaviors. Machine learning (ML) models, which shown great potential in monitoring insects behaviors, have recently been used to speed up this process. However, most publicly available tools that provide automatic annotation suffer from low prediction accuracy due to only using simple distinction rules to classify waveforms. For this reason, we developDiscoEPG, an open-source Python package which performs accurate automatic EPG signal annotation. Various ML algorithms were experimented rigorously, which reports greater prediction power and improved accuracy in comparison to previous studies. In addition, we equipped our package with novel tools for generating journal-level plots to facilitate visual inspection, while including the computation of various EPG parameters and necessary statistical analysis which are popular in the research of aphids. WithDiscoEPG, we aim to facilitate the rapid characterization of analysis of piercing-sucking insects feeding behavior through EPG signal, making this technique more viable to researchers who share the same interest. Our package is publicly available at:https://github.com/HySonLab/ML4Insects.
Defining a highly conserved B cell epitope in the receptor binding motif of SARS-CoV-2 spike glycoprotein
Authors: Malladi Sameer Kumar , Jaiswal Deepika , Ying Baoling , Alsoussi Wafaa B. , Darling Tamarand L. , Dadonaite Bernadeta , Civljak Alesandro , Horvath Stephen C. , Zhou Julian Q. , Kim Wooseob , Turner Jackson S. , Schmitz Aaron J. , Han Fangjie , Scheaffer Suzanne M. , Farnsworth Christopher W. , Nachbagauer Raffael , Nestorova Biliana , Chalkias Spyros , Klebert Michael K. , Edwards Darin K. , Paris Robert , Strnad Benjamin S. , Middleton William D. , O’Halloran Jane A. , Presti Rachel M. , Bloom Jesse D. , Boon Adrianus C. M. , Diamond Michael S. , Bajic Goran , Ellebedy Ali H.
Published: December 2024

SARS-CoV-2 mRNA vaccines induce robust and persistent germinal centre (GC) B cell responses in humans. It remains unclear how the continuous evolution of the virus impacts the breadth of the induced GC B cell response. Using ultrasound-guided fine needle aspiration, we examined draining lymph nodes of nine healthy adults following bivalent booster immunization. We show that 77.8% of the B cell clones in the GC expressed as representative monoclonal antibodies recognized the spike protein, with a third (37.8%) of these targeting the receptor binding domain (RBD). Strikingly, only one RBD-targeting mAb, mAb-52, neutralized all tested SARS- CoV-2 strains, including the recent KP.2 variant. mAb-52 utilizes the IGHV3-66 public clonotype, protects hamsters challenged against the EG.5.1 variant and targets the class I/II RBD epitope, closely mimicking the binding footprint of ACE2. Finally, we show that the remarkable breadth of mAb-52 is due to the somatic hypermutations accumulated within vaccine-induced GC reaction.

One Sentence Summary

Booster SARS-CoV-2 mRNA vaccine recruits and broadens GC B cell responses targeting a highly conserved site on receptor binding domain of spike glycoprotein.
Vocal species are more central in Eastern Himalayan Mixed-Species bird flocks
Authors: Gupta Satyam , Bharadwaj Akshay , Bhat Akshiti , Thapa Aiti , Biswakarma Aman , Tamang Bharat , Munda Binod , Biswakarma Biren , Tamang Dema , Pradhan Dambar , Rai Mangal K , Rai Rohit , Rai Shambh , Srinivasan Umesh
Published: December 2024

Mixed-species flocks (MSF) represent an important form of social organisation in bird communities worldwide. Despite its likely importance in flock formation and cohesion, the role of vocal communication in the formation and maintenance of MSF in birds is hitherto understudied. In this study, we examine if a species’ centrality within a mixed-species flock is influenced by its vocal behaviour during the dawn chorus, i.e., the time of MSF formation. Using acoustic sampling and field observation, we studied bird species found in MSF in the Eastern Himalayas. Our results show differential vocal activity patterns among MSF-forming bird species and suggest a positive correlation between calling rates and closeness centrality in understory MSFs. We also found a more synchronised vocalisation pattern in the understory MSFs, with a consistent peak in vocal activity in the early morning hours, whereas no consistent vocal pattern was found for canopy flocks. Overall, our results suggest a potential mechanism that drives MSF formation wherein the vocal activity of central species precedes and likely attracts participation from other attendant species.
Multi-omic integration with human DRG proteomics highlights TNFα signalling as a relevant sexually dimorphic pathway
Authors: Barry Allison M , Sondermann Julia R , Lesnak Joseph B , Xian Feng , Franco-Enzástiga Úrzula , O’Brien Jayden A , Varela David Gomez , Schackmuth Morgan K , Shiers Stephanie , Price Theodore J , Schmidt Manuela
Published: December 2024

The peripheral nervous system has been widely implicated in pathological conditions that exhibit distinct clinical presentations in men and women, most notably in chronic pain disorders. Here, we explored this sexual dimorphism at a molecular level. We expanded the available omics landscape in the PNS to include quantitative proteomics of the human dorsal root ganglia (hDRG) and nerve. Using data-independent acquisition mass spectrometry, we uncovered an extensive protein landscape, validated against tissue-specific differences between the nerve and hDRG. Using a combination of multi-omic analyses andin vitrofunctional support, we then examined sex-differences, highlighting TNFα signalling as a relevant sexually dimorphic pathway in males. These results support a functional sexually dimorphism in the periphery, which is of particular importance to sensory– and pain-related clinical translation.
Rates of evolution differ between cell types identified by single-cell RNAseq in threespine stickleback
Authors: Rodgers Maria L. , Subramanian Swapna , Fuess Lauren E. , He Wan , Scarpino Samuel V. , Roth-Monzón Andrea J. , Jeffries Daniel , Seignon Martine , Milligan-McClellan Kathryn , Carrier Rebecca , Steinel Natalie C. , Bolnick Daniel I.
Published: December 2024

Rates of evolutionary change vary by gene. While some broad gene categories are highly conserved with little divergence over time, others undergo continuous selection pressure and are highly divergent. Here, we combine single-cell RNA sequencing (scRNAseq) with evolutionary genomics to understand whether certain cell types exhibit faster evolutionary divergence (using their characteristic genes), than other types of cells. Merging scRNAseq with population genomic data, we show that cell types differ in the rate at which their characteristic genes evolve, as measured by allele frequency divergence among many populations (FST) and between species (dN/dS ratios). Neutrophils, B cells, and fibroblasts exhibit elevated FSTat characteristic genes, while eosinophils in the intestine and thrombocytes in the head kidney exhibit lower FSTthan the average for 1000 random genes. Gene network centrality also differed between immune- and non-immune-associated genes, and closeness centrality was positively related to gene FST. These results highlight the value of merging single cell RNA sequencing technology with evolutionary population genomic data, and reveal that genes which define immune cell types exhibit especially rapid evolution.
DDI-GPT: Explainable Prediction of Drug-Drug Interactions using Large Language Models enhanced with Knowledge Graphs
Authors: Xu Chengqi , Bulusu Krishna C. , Pan Heng , Elemento Olivier
Published: December 2024

Identifying potential drug-drug interactions (DDIs) before clinical use is essential for patient safety yet remains a significant challenge in drug development. We presented DDI-GPT, a deep learning framework that predicts DDIs by combining knowledge graphs (KGs) and pre-trained large language models (LLMs), enabling early detection of potential drug interactions. We demonstrated that DDI-GPT outperforms current state-of-the-art methods by capturing contextual dependencies between biomedical entities to infer potential DDIs. Through feature attribution methods, we show that our explainable deep learning (DL) models enhance the quality of explanations on the pathways and interactome networks. Using TwoSIDES as our benchmark dataset, DDI-GPT achieved the best performance of 0.964 in AUROC compared with existing DL methods. We also applied DDI-GPT to perform zero-shot prediction on 9,480 DDI records, encompassing 442 distinct drugs from the FDA Adverse Event Reporting System. DDI-GPT can attain a high accuracy of in 0.84 AUROC, with an improvement of 14% compared to the best previously published method. We explored model interpretations on predicted DDIs involving Bruton’s tyrosine kinase (BTK) inhibitors and uncovered CYP3A-enriched signals underlying the contaminant use of BTK inhibitors with other drugs leading to toxicity. Altogether, DDI-GPT, implemented as both a web server platform and a software package, identifies DDI events and offers a deep learning tool for drug safety use with expandable features.
Universal Single Copy Knock-In System inCaenorhabditis elegans: One Plasmid to Target All Chromosomes
Authors: Dinneen Erica , Silva-García Carlos G.
Published: December 2024

Successful transgenesis in model organisms has dramatically helped us understand gene function, regulation, genetic networks, and potential applications. Here, we introduce the universal single-copy knock-in system (Universal SKI System or U-SKI), designed for inserting any transgene by CRISPR/Cas9 in theCaenorhabditis elegansgenome. The Universal SKI System takes advantage of a plasmid (pSKI), which can also be used for extrachromosomal arrays, to facilitate the insertion of a transgene at specific safe harbor loci on each autosomal chromosome. The pSKI plasmid contains multiple restriction sites for easy cloning and serves as a CRISPR/Cas9-based insertion repair template because it has two synthetic and long homology arms that recombine with the SKI cassettes. This system also uses a single crRNA guide, which acts as a Co-CRISPR enrichment marker. Overall, the Universal SKI System is highly flexible; with the same Universal SKI cassette on each autosome, researchers can select the insertion site and streamline tracking while reducing the complexity of expressing single-copy transgenes inC. elegans.
Cobalt induces the set-up of new structural networks in river biofilms: Impairment of autotrophic-heterotrophic coupling
Authors: Gourgues Sarah , Goñi-Urriza Marisol , Baldoni-Andrey Patrick , Bagger Gurieff Nicholas , Gelber Clémentine , Le Faucheur Séverine
Published: December 2024

Biofilms play a crucial role in biogeochemical cycles, making them essential to the functionality and stability of aquatic ecosystems. Their functioning is mainly driven by interactions between microorganisms that ensure the cycling of major elements. Evaluating the impact of stressors, such as metals, on these interactions is challenging. This study examined the effects of cobalt (Co) on the microeukaryotic community and their relationships with prokaryotes within biofilms grown in the presence of several Co concentrations (background concentrations, 0.1, 0.5, and 1 µM) for 28 days and 35 days after the end of Co injection. A previous work has suggested thatCyanobacteriawere highly sensitive to Co leading to a reduction of the photosynthetic potential of the biofilm. In this study, the major primary producers, namelyBacillariophyceae,were also found to be sensitive to Co. The direct consequence of this sensitivity was an impairment of the autotroph-heterotroph coupling and the dominance of prokaryotic taxa in microbe-microbe interactions. The biofilms co-occurrence networks were then smaller, less connected but more centralized at 1 µM Co. Keystones, that were half affiliated with microalgae in the absence of Co, were mostly prokaryotes. As such, prokaryotes were found to control resource production and element cycling in Co-stressed biofilms. These changes in co-occurrence network organization and microbial community composition demonstrated a cascade of effects related to contamination in rivers. Our results further highlighted the strategy biofilms adopt to counteract the impairment of autotroph-heterotroph coupling, and to maintain their functions and ecosystemic roles in contaminated environments.
Identification of Gene Targets for the Sprouting Inhibitor CIPC
Authors: Grand Thomas M , Pitman James K , Williams Alexander L , Smith Lisa M , Fleming Andrew J
Published: December 2024

Sprout suppressants are widely used in industry to ensure year-round availability of potato tubers, significantly decreasing wastage by repressing premature growth of buds on the tuber surface during storage. Despite its ban from 2020 in the EU, isopropyl N-(3- chlorophenyl) carbamate (also known as chlorpropham or CIPC) remains the most widely used suppressant world-wide. However, the mechanism of action of CIPC remains obscure. Here we report on a combined targeted transcriptomic and genetic approach to identify components in the tuber bud cell-division machinery that might be involved in CIPC’s mode of action. This involved RNAseq analysis of dissected, staged tuber buds during in vitro sprouting with and without CIPC to identify lead genes, followed by the development and application of an Arabidopsis root assay to assess cell division response to CIPC in selected mutants. The ease of use of this model plant, coupled with its immense genetic resources, allowed us to test the functionality of lead genes encoding cell-division associated proteins in the modulation of plant growth response to CIPC. This approach led to the identification of a component of the augmin complex (a core player in mitosis) as a potential target for CIPC.