bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro generated antibodies guide thermostable ADDomer nanoparticle design for nasal vaccination and passive immunization against SARS-CoV-2
Authors: Buzas Dora , Bunzel Adrian H , Staufer Oskar , Milodowski Emily J , Edmunds Grace L , Bufton Joshua C , Vidana Mateo Beatriz V , Yadav Sathish K N , Gupta Kapil , Fletcher Charlotte , Williamson Maia K , Harrison Alexandra , Borucu Ufuk , Capin Julien , Francis Ore , Balchin Georgia , Hall Sophie , Vega Mirella V , Durbesson Fabien , Lingappa Srikanth , Vincentelli Renaud , Roe Joe , Wooldridge Linda , Burt Rachel , Anderson Ross J L , Mulholland Adrian J , Bristol UNCOVER Group  , Hare Jonathan , Bailey Mick , Davidson Andrew D , Finn Adam , Morgan David , Mann Jamie , Spatz Joachim , Garzoni Frederic , Schaffitzel Christiane , Berger Imre 
Published: October 2023

Abstract

Background
Due to COVID-19, pandemic preparedness emerges as a key imperative, necessitating new approaches to accelerate development of reagents against infectious pathogens.

Methods
Here, we developed an integrated approach combining synthetic, computational and structural methods with in vitro antibody selection and in vivo immunization to design, produce and validate nature-inspired nanoparticle-based reagents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Results
Our approach resulted in two innovations: (i) a thermostable nasal vaccine called ADDoCoV, displaying multiple copies of a SARS-CoV-2 receptor binding motif derived epitope and (ii) a multivalent nanoparticle superbinder, called Gigabody, against SARS-CoV-2 including immune-evasive variants of concern (VOCs). In vitro generated neutralizing nanobodies and electron cryo-microscopy established authenticity and accessibility of epitopes displayed by ADDoCoV. Gigabody comprising multimerized nanobodies prevented SARS-CoV-2 virion attachment with picomolar EC50. Vaccinating mice resulted in antibodies cross-reacting with VOCs including Delta and Omicron.

Conclusion
Our study elucidates Adenovirus-derived dodecamer (ADDomer)-based nanoparticles for use in active and passive immunization and provides a blueprint for crafting reagents to combat respiratory viral infections.
Geographic Variation, Economic Activity, and Labor Market Characteristics in Trajectories of Suicide in the United States, 2008–2020
Authors: Keyes Katherine M , Kandula Sasikiran , Martinez-Ales Gonzalo , Gimbrone Catherine , Joseph Victoria , Monnat Shannon , Rutherford Caroline , Olfson Mark , Gould Madelyn , Shaman Jeffrey 
Published: October 2023

Abstract
Suicide rates in the United States have increased over the past 15 years, with substantial geographic variation in these increases; yet there have been few attempts to cluster counties by the magnitude of suicide rate changes according to intercept and slope or to identify the economic precursors of increases. We used vital statistics data and growth mixture models to identify clusters of counties by their magnitude of suicide growth from 2008 to 2020 and examined associations with county economic and labor indices. Our models identified 5 clusters, each differentiated by intercept and slope magnitude, with the highest-rate cluster (4% of counties) being observed mainly in sparsely populated areas in the West and Alaska, starting the time series at 25.4 suicides per 100,000 population, and exhibiting the steepest increase in slope (0.69/100,000/year). There was no cluster for which the suicide rate was stable or declining. Counties in the highest-rate cluster were more likely to have agricultural and service economies and less likely to have urban professional economies. Given the increased burden of suicide, with no clusters of counties improving over time, additional policy and prevention efforts are needed, particularly targeted at rural areas in the West.
Semla: a versatile toolkit for spatially resolved transcriptomics analysis and visualization
Authors: Larsson Ludvig , Franzén Lovisa , Ståhl Patrik L , Lundeberg Joakim 
Published: October 2023

Abstract

Summary
Spatially resolved transcriptomics technologies generate gene expression data with retained positional information from a tissue section, often accompanied by a corresponding histological image. Computational tools should make it effortless to incorporate spatial information into data analyses and present analysis results in their histological context. Here, we present semla, an R package for processing, analysis, and visualization of spatially resolved transcriptomics data generated by the Visium platform, that includes interactive web applications for data exploration and tissue annotation.

Availability and implementation
The R package semla is available on GitHub (https://github.com/ludvigla/semla), under the MIT License, and deposited on Zenodo (https://doi.org/10.5281/zenodo.8321645). Documentation and tutorials with detailed descriptions of usage can be found at https://ludvigla.github.io/semla/.
PICKLUSTER: a protein-interface clustering and analysis plug-in for UCSF ChimeraX
Authors: Genz Luca R , Mulvaney Thomas , Nair Sanjana , Topf Maya 
Published: October 2023

Abstract

Summary
The identification and characterization of interfaces in protein complexes is crucial for understanding the mechanisms of molecular recognition. These interfaces are also attractive targets for protein inhibition. However, targeting protein interfaces can be challenging for large interfaces that consist of multiple interacting regions. We present PICKLUSTER [Protein Interface C(K)luster]—a program for identifying “sub-interfaces” in protein–protein complexes using distance clustering. The division of the interface into smaller “sub-interfaces” offers a more focused approach for targeting protein–protein interfaces.

Availability and implementation
PICKLUSTER is implemented as a plug-in for the molecular visualization program UCSF ChimeraX 1.4 and subsequent versions. It is freely available for download in the ChimeraX Toolshed and https://gitlab.com/topf-lab/pickluster.git.
Safety of biologic therapy in combination with methotrexate in moderate to severe psoriasis: a cohort study from the BIOBADADERM registry
Authors: Lluch-Galcerá Juan José , Carrascosa Jose Manuel , González-Quesada Alicia , Rivera-Díaz Raquel , Sahuquillo-Torralba Antonio , Llamas-Velasco Mar , Gómez-García Francisco José , Herrera-Acosta Enrique , de la Cueva Pablo , Baniandrés-Rodríguez Ofelia , Lopez-Estebaranz Jose Luis , Belinchón Isabel , Ferrán Marta , Mateu Almudena , Rodríguez Lourdes , Riera-Monroig Josep , Abalde-Pintos M Teresa , Carretero Gregorio , García-Donoso Carmen , Pujol-Marco Conrad , Del Alcázar Elena , Santamaría-Domínguez Cristina , Suárez-Pérez Jorge Alonso , Nieto-Benito Lula María , Ruiz-Genao Diana Patricia , Salgado-Boquete Laura , Descalzo Miguel Ángel , García-Doval Ignacio 
Published: October 2023

Abstract

Background
Safety is an important consideration in decisions on treatment for patients with moderate-to-severe psoriasis and the study of drug safety is the main purpose of the BIOBADADERM registry. The combination of a biologic agent and a conventional systemic drug [generally methotrexate (MTX)] is a common treatment in clinical practice. However, there is a paucity of evidence from real-world practice on the safety of such combination regimens in the treatment of psoriasis.

Objectives
The primary objective of this study was to ascertain whether the use of regimens combining biologic drugs with MTX in the management of moderate-to-severe psoriasis increases the risk of adverse events (AEs) or serious AEs (SAEs). We compared monotherapy using tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors with the use of the same drugs in combination with MTX.

Methods
Using data from the BIOBADADERM registry, we compared biologic monotherapies with therapies that were combined with MTX. We estimated adjusted incidence rate ratios (aIRR) using a random effects Poisson regression with 95% confidence intervals for all AEs, SAEs, infections and serious infections and other AEs by system organ class.

Results
We analysed data from 2829 patients and 5441 treatment cycles, a total of 12 853 patient-years. The combination of a biologic with MTX was not associated with statistically significant increases in overall risk of AEs or SAEs in any treatment group. No increase in the total number of infections or serious infections in patients receiving combined therapy was observed for any group. However, treatment with a TNF inhibitor combined with MTX was associated with an increase in the incidence of gastrointestinal AEs (aIRR 2.50, 95% CI 1.57–3.98; P &lt; 0.002).

Conclusions
The risk of AEs and SAEs was not significantly increased in patients with moderate-to-severe psoriasis receiving different classes of biologic drugs combined with MTX compared with those on biologic monotherapy.
A critical role of the endothelial S-phase kinase-associated protein 2/phosphatase and tensin homologue axis in angiogenesis and psoriasis
Authors: Xie Xinya , Cui Qi , Jiang Tingting , Zhao Ziwei , Liu Zheyi , Liu Jia , Yao Qinyu , Wang Yuxin , Dang Erle , Wang Gang , Xiao Lei , Wang Nanping 
Published: October 2023

Abstract

Background
Psoriasis is a common chronic skin disorder. Pathologically, it features abnormal epidermal proliferation, infiltrating inflammatory cells and increased angiogenesis in the dermis. Aberrant expression of E3 ubiquitin ligase and a dysregulated protein ubiquitination system are implicated in the pathogenesis of psoriasis.

Objectives
To examine the potential role of S-phase kinase-associated protein 2 (Skp2), an E3 ligase and oncogene, in psoriasis.

Methods
Gene expression and protein levels were evaluated with quantitative reverse transcriptase polymerase chain reaction, Western blotting, immunohistochemistry and immunofluorescence staining of skin samples from patients with psoriasis vulgaris and an imiquimod (IMQ)-induced mouse model, as well as from cultured endothelial cells (ECs). Protein interaction, substrate ubiquitination and degradation were examined using co-immunoprecipitation, Western blotting and a cycloheximide chase assay in human umbilical vein ECs. Angiogenesis was measured in vitro using human dermal microvascular ECs (HDMECs) for BrdU incorporation, migration and tube formation. In vivo angiogenesis assays included chick embryonic chorioallantoic membrane, the Matrigel plug assay and quantification of vasculature in the mouse lesions. Skp2 gene global knockout (KO) mice and endothelial-specific conditional KO mice were used.

Results
Skp2 was increased in skin samples from patients with psoriasis and IMQ-induced mouse lesions. Immunofluorescent double staining indicated a close association of Skp2 expression with excessive vascularity in the lesional dermal papillae. In HDMECs, Skp2 overexpression was enhanced, whereas Skp2 knockdown inhibited EC proliferation, migration and tube-like structure formation. Mechanistically, phosphatase and tensin homologue (PTEN), which suppresses the phosphoinositide 3-kinase/Akt pathway, was identified to be a novel substrate for Skp2-mediated ubiquitination. A selective inhibitor of Skp2 (C1) or Skp2 small interfering RNA significantly reduced vascular endothelial growth factor-triggered PTEN ubiquitination and degradation. In addition, Skp2-mediated ubiquitination depended on the phosphorylation of PTEN by glycogen synthase kinase 3β. In the mouse model, Skp2 gene deficiency alleviated IMQ-induced psoriasis. Importantly, tamoxifen-induced endothelial-specific Skp2 KO mice developed significantly ameliorated psoriasis with diminished angiogenesis of papillae. Furthermore, topical use of the Skp2 inhibitor C1 effectively prevented the experimental psoriasis.

Conclusions
The Skp2/PTEN axis may play an important role in psoriasis-associated angiogenesis. Thus, targeting Skp2-driven angiogenesis may be a potential approach to treating psoriasis.
Determining the role of novel metabolic pathways in driving intracranial pressure reduction after weight loss
Authors: Alimajstorovic Zerin , Mitchell James L , Yiangou Andreas , Hancox Thomas , Southam Andrew D , Grech Olivia , Ottridge Ryan , Winder Catherine L , Tahrani Abd A , Tan Tricia M , Mollan Susan P , Dunn Warwick B , Sinclair Alexandra J 
Published: October 2023

Abstract
Idiopathic intracranial hypertension, a disease classically occurring in women with obesity, is characterized by raised intracranial pressure. Weight loss leads to the reduction in intracranial pressure. Additionally, pharmacological glucagon-like peptide-1 agonism reduces cerebrospinal fluid secretion and intracranial pressure. The potential mechanisms by which weight loss reduces intracranial pressure are unknown and were the focus of this study. Meal stimulation tests (fasted plasma sample, then samples at 15, 30, 60, 90 and 120 min following a standardized meal) were conducted pre- and post-bariatric surgery [early (2 weeks) and late (12 months)] in patients with active idiopathic intracranial hypertension. Dynamic changes in gut neuropeptides (glucagon-like peptide-1, gastric inhibitory polypeptide and ghrelin) and metabolites (untargeted ultra-high performance liquid chromatography-mass spectrometry) were evaluated. We determined the relationship between gut neuropeptides, metabolites and intracranial pressure. Eighteen idiopathic intracranial hypertension patients were included [Roux-en-Y gastric bypass (RYGB) n = 7, gastric banding n = 6 or sleeve gastrectomy n = 5]. At 2 weeks post-bariatric surgery, despite similar weight loss, RYGB had a 2-fold (50%) greater reduction in intracranial pressure compared to sleeve. Increased meal-stimulated glucagon-like peptide-1 secretion was observed after RYGB (+600%) compared to sleeve (+319%). There was no change in gastric inhibitory polypeptide and ghrelin. Dynamic changes in meal-stimulated metabolites after bariatric surgery consistently identified changes in lipid metabolites, predominantly ceramides, glycerophospholipids and lysoglycerophospholipids, which correlated with intracranial pressure. A greater number of differential lipid metabolites were observed in the RYGB cohort at 2 weeks, and these also correlated with intracranial pressure. In idiopathic intracranial hypertension, we identified novel changes in lipid metabolites and meal-stimulated glucagon-like peptide-1 levels following bariatric surgery which were associated with changes in intracranial pressure. RYGB was most effective at reducing intracranial pressure despite analogous weight loss to gastric sleeve at 2 weeks post-surgery and was associated with more pronounced changes in these metabolite pathways. We suggest that these novel perturbations in lipid metabolism and glucagon-like peptide-1 secretion are mechanistically important in driving a reduction in intracranial pressure following weight loss in patients with idiopathic intracranial hypertension. Therapeutic targeting of these pathways, for example with glucagon-like peptide-1 agonist infusion, could represent a therapeutic strategy.
Expanding the phenotypic spectrum of CLCN2-related leucoencephalopathy and ataxia
Authors: Nóbrega Paulo R , R. B. de Paiva Anderson , Souza Katiane S , de Souza Jorge Luiz B , G. S. B. Lima Pedro Lucas , da Silva Delson José , Pitombeira Milena Sales , Borges Viviennee K , Dias Daniel A , Bispo Luciana M , Santos Carolina F , Freua Fernando , Silva Paulo Diego S , Alves Isabela S , Portella Leonardo B , Cunha Paulina R , Salomao Rubens Paulo A , Pedroso José Luiz , Miyajima Veridiana P , Miyajima Fábio , Cali Elisa , Wade Charles , Sudarsanam Annapurna , O’Driscoll Mary , Hayton Tom , Barsottini Orlando G P , Klebe Stephan , Kok Fernando , Lucato Leandro Tavares , Houlden Henry , Depienne Christel , Lynch David S , Braga-Neto Pedro 
Published: October 2023

Abstract
Mutations in CLCN2 are a rare cause of autosomal recessive leucoencephalopathy with ataxia and specific imaging abnormalities. Very few cases have been reported to date. Here, we describe the clinical and imaging phenotype of 12 additional CLCN2 patients and expand the known phenotypic spectrum of this disorder. Informed consent was obtained for all patients. Patients underwent either whole-exome sequencing or focused/panel-based sequencing to identify variants. Twelve patients with biallelic CLCN2 variants are described. This includes three novel likely pathogenic missense variants. All patients demonstrated typical MRI changes, including hyperintensity on T2-weighted images in the posterior limbs of the internal capsules, midbrain cerebral peduncles, middle cerebellar peduncles and cerebral white matter. Clinical features included a variable combination of ataxia, headache, spasticity, seizures and other symptoms with a broad range of age of onset. This report is now the largest case series of patients with CLCN2-related leucoencephalopathy and reinforces the finding that, although the imaging appearance is uniform, the phenotypic expression of this disorder is highly heterogeneous. Our findings expand the phenotypic spectrum of CLCN2-related leucoencephalopathy by adding prominent seizures, severe spastic paraplegia and developmental delay.
Functional brain connectivity in young adults with post-stroke epilepsy
Authors: Boot Esther M , Omes Quinty P M , Maaijwee Noortje , Schaapsmeerders Pauline , Arntz Renate M , Rutten-Jacobs Loes C A , Kessels Roy P C , de Leeuw Frank-Erik , Tuladhar Anil M 
Published: October 2023

Abstract
Approximately 1 in 10 young stroke patients (18–50 years) will develop post-stroke epilepsy, which is associated with cognitive impairment. While previous studies have shown altered brain connectivity in patients with epilepsy, little is however known about the changes in functional brain connectivity in young stroke patients with post-stroke epilepsy and their relationship with cognitive impairment. Therefore, we aimed to investigate whether young ischaemic stroke patients have altered functional networks and whether this alteration is related to cognitive impairment. We included 164 participants with a first-ever cerebral infarction at young age (18–50 years), along with 77 age- and sex-matched controls, from the Follow-Up of Transient Ischemic Attack and Stroke patients and Unelucidated Risk Factor Evaluation study. All participants underwent neuropsychological testing and resting-state functional MRI to generate functional connectivity networks. At follow-up (10.5 years after the index event), 23 participants developed post-stroke epilepsy. Graph theoretical analysis revealed functional network reorganization in participants with post-stroke epilepsy, in whom a weaker (i.e. network strength), less-integrated (i.e. global efficiency) and less-segregated (i.e. clustering coefficient and local efficiency) functional network was observed compared with the participants without post-stroke epilepsy group and the controls (P &lt; 0.05). Regional analysis showed a trend towards decreased clustering coefficient, local efficiency and nodal efficiency in contralesional brain regions, including the caudal anterior cingulate cortex, posterior cingulate cortex, precuneus, superior frontal gyrus and insula in participants with post-stroke epilepsy compared with those without post-stroke epilepsy. Furthermore, participants with post-stroke epilepsy more often had impairment in the processing speed domain than the group without post-stroke epilepsy, in whom the network properties of the precuneus were positively associated with processing speed performance. Our findings suggest that post-stroke epilepsy is associated with functional reorganization of the brain network after stroke that is characterized by a weaker, less-integrated and less-segregated brain network in young ischaemic stroke patients compared with patients without post-stroke epilepsy. The contralesional brain regions, which are mostly considered as hub regions, might be particularly involved in the altered functional network and may contribute to cognitive impairment in post-stroke epilepsy patients. Overall, our findings provide additional evidence for a potential role of disrupted functional network as underlying pathophysiological mechanism for cognitive impairment in patients with post-stroke epilepsy.
Dermoscopy as a diagnostic aid in pityriasis lichenoides et varioliformis acuta
Authors: Peñuelas Leal Rodrigo , Labrandero Hoyos Carolina , Grau Echevarría Andrés , Blaya Imbernon Daniel , Finello Malena , Magdaleno Tapial Jorge , Alegre De Miguel Victor 
Published: October 2023

AbstractDiagnosis of pityriasis lichenoides et varioliformis acuta (PLEVA) is based on the characteristic pattern of lesions in different stages of development, ranging from erythematous maculopapules to papules with a crusted and/or necrotic centre. However, it may raise the differential diagnosis with other entities. It is therefore not uncommon to have to perform skin biopsies to reach a diagnosis, including in infants. In this study, we report the cases of three patients with PLEVA, highlighting the correlations between the clinical, dermoscopic and histological features. Observation of the dermatoscopic findings described, such as punctate or glomerular vessels and erythematous globules surrounding a homogeneous orange or crusty central area, may allow for a rapid diagnosis, avoiding the need for invasive techniques.
Reflectance confocal microscopy as a complementary diagnostic tool for greyish-brown dermatoses in children
Authors: Chen Lixin , Wang Ying , Gao Xibo , Li Qinfeng 
Published: October 2023

Abstract
Mastocytosis, lichen planus pigmentosus (LPP), fixed drug eruption (FDE) and café-au-lait macules (CALM) have a similar appearance, often lead to misdiagnosis and missed diagnoses. At the outpatient clinic at Tianjin Children’s Hospital in 21 patients with mastocytosis, 18 with LPP, 11 with FDE and 12 with CALM we evaluated the characteristics and distinguishing features of their dermatoses using reflectance confocal microscopy (RCM). In mastocytosis, the dermal papillary rings generally had a significantly increased bright refractive index and the superficial dermis was filled with moderate refractive flocculent material. In LPP, the dermal papillary rings were absent and numerous different-sized cellular structures were densely distributed in the superficial dermis. In FDE, the dermal papillary rings were intact with a significantly increased bright refractive index. In CALM, normal dermal papillary rings were detected with a uniformly slightly increased refractive index and no obvious abnormality in the superficial dermis. RCM allows for real-time visualization of the major key diagnostic and distinguishing features of four greyish-brown dermatoses in children.