bluuebunny/crossref_metadata_2025_split huggingface dataset:
719 - Modulating Nav1.8-expressing neurons offers promising direction to address symptoms of atopic dermatitis
Authors: Scoles Madeline C , Wang Jacqueline C , Sung Winnie , Olivarez Mason , Liu Ellen , Lev Emmy , Shah Rishi B , Kim Seongmin , Kaplan Nihal , Paller Amy S 
Published: August 2024

Abstract

Introduction/Background
Atopic dermatitis (AD) is an inflammatory skin condition characterized by eczematous lesions, itch and pain. The inflammation and itch associated with AD are caused in part by dysregulation of neuroimmune circuits. Understanding these circuits is crucial for comprehending the pathophysiology of AD. Nav1.8 is a sodium channel expressed on C afferent fibers in the dorsal root ganglia (DRG). Knockdown of signaling pathways in Nav1.8+ nerves has been previously shown to reduce severity of AD in mice.

Objectives
We hypothesized that ablating Nav1.8 receptor-expressing neurons would lead to reduced severity of AD symptoms including itch and pain, and decreased expression of AD-related genes in a mouse model for AD.

Methods
Mice expressing iDTR (diphtheria toxin receptor) under the control of Nav1.8-Cre were used. Diphtheria toxin (DTX) was injected to ablate Nav1.8+ nerves and phosphate-buffered saline (PBS) was injected as a control. We achieved AD-like symptoms in both Nav1.8-ablated mice and control mice using topically-applied MC903 to mouse shaved nape skin.

Results
We noted no obvious clinical differences between Nav1.8-ablated mice and control mice skin. We found that Nav1.8+ ablation resulted in a ∼70% (p&lt;0.05) reduction in scratching behavior and ∼40% (p=0.05) reduction in pain-related behaviors compared to control mice with intact Nav1.8. Nav1.8-nerve ablation similarly resulted in reduced expression of Tac1 (substance P – a neuropeptide known to mediate itch signaling) (p&lt;0.05) and Il31ra (an itch-related cytokine receptor) (p&lt;0.05) in Nav1.8-ablated mouse DRG tissue. However, we see no changes in expression of AD-related cytokines in Nav1.8-ablated nape skin tissue compared to control skin, including Il4, Il13, Il31, and Tslp.

Conclusions
These results suggest that Nav1.8-expressing neurons play a key role in the itch and pain associated with AD, but may have no effect on AD-induced cutaneous inflammation. These findings could offer a promising new direction for further research into treatments targeting the itch and pain caused by AD.
Adrenal gland haemangioma, a rare entity difficult to differentiate from malignancy
Authors: López Gómez Paola , Paniagua Gonzalez Miguel , García Pérez Angela , Mullor Delgado Luis Alberto 
Published: August 2024

Abstract
Adrenal haemangioma is a rare benign vascular lesion, which is usually asymptomatic and it is typically discovered incidentally on radiographic imaging. Differential diagnosis from other benign or malignant adrenal neoplasms may be challenging, and in many cases, the diagnosis is only possible after surgical resection. We present a case of a 39-year-old female with abdominal pain in the upper right quadrant, who was referred to our hospital after incidentally discovering a mass above the right kidney on abdominal ultrasonography. MRI revealed an adrenal mass, with features not indicative of adenoma and suggestive of adrenal haemangioma, without ruling out other possible diagnoses such us phaeochromocytoma and adrenal cortical carcinoma. Biochemical tests did not reveal any endocrine dysfunction. The patient underwent adrenalectomy, and histopathological analysis confirmed a venous haemangioma. Adrenal gland haemangioma is an unusual vascular lesion, typically diagnosed incidentally during abdominal imaging. Certain radiologic features may raise suspicion for malignancy, making it difficult to distinguish them from a primary adrenal cortical carcinoma. They may also grow large, compressing surrounding structures and causing abdominal pain, or may rupture, leading to retroperitoneal haemorrhage. For these reasons, some authors recommend excision of all suspected adrenal haemangiomas, and in many cases, the final diagnosis is made only after surgical removal.
The migration history of the Kamchatka rhododendron (Therorhodion camtschaticum s.l.) indicates two distinct dispersal routes towards Eastern Beringia
Authors: Polezhaeva Maria A , Modorov Makar V , Mochalova Olga A , Ickert-Bond Stefanie M 
Published: August 2024

Abstract
The Kamchatka rhododendron (Therorhodion camtschaticum s.l.) is a small, cold-resistant arcto-alpine shrub species with a controversial taxonomy and a wide Beringian distribution, from northern Eurasia to Arctic North America. Some authors regard T. camtschaticum and the closely related Therorhodion glandulosum as separate species while others suggest that they represent regionally differentiated subspecies. In order to resolve this relationship, we sampled 33 populations within the native species ranges, using three fragments of plastid DNA (ptDNA) and ten nuclear microsatellites (nSSR). We recovered two genetic lineages consistent with species rather than subspecies. The distribution of these genetic lineages are consistent with two different migration pathways of species from western Beringia to eastern Beringia: (i) for T. glandulosum a northern pathway from northern East Asia to the Seward Peninsula in northern Alaska; and (ii) for T. camtschaticum a southern pathway from the southern part of western Beringia to the Aleutian Islands and the seashore of south-east Alaska. The northern route extends from the Okhotsk seashore through the Kolyma region, Chukotka, and central and northern Kamchatka. The southern route begins at the Sikhote-Alin ridge, and goes through Sakhalin Island, the Kuril Islands, and southern Kamchatka. Demographic analysis using nSSR data inferred a divergence time between T. camtschaticum and T. glandulosum long before the Last Glacial Maximum.
Elevated expression of Golgi Transport 1B promotes the progression of cervical cancer by activating the NF-kappaB signaling pathway via interaction with TANK-Binding Kinase 1
Authors: Sun Yixuan , Peng Qihua , Wang Ruiwen , Yin Yifan , Mutailifu Musitaba , Hu Lipeng , Teng Yincheng , Zhou Yang 
Published: August 2024

Abstract
As a preventable disease, cervical cancer (cervical squamous cell carcinoma and endocervical adenocarcinoma—CESC) remains a tumor with high morbidity and mortality worldwide, underscoring the pressing need for effective treatment strategies. This research identified Golgi transport 1B (GOLT1B) as a critical gene involved in the development of cervical cancer. Gene Expression Omnibus (GEO) datasets were investigated to determine the upregulation of GOLT1B in cervical cancer tissue compared with normal tissue. Besides, GOLT1B was found to predict poor prognosis in cervical cancer by utilizing Gene Expression Profiling Interactive Analysis (GEPIA). The functional assay indicated that GOLT1B promoted CESC viability and migration in vitro and in vivo. RNA sequencing results suggested that GOLT1B likely influenced the nuclear factor-kappaB (NF-κB) pathway. The subsequent western blot and dual luciferase reporter assay revealed the interaction between GOLT1B and TANK binding kinase 1 (TBK1), modulating the NF-κB pathway. More importantly, GOLT1B was also found to regulate immune cell infiltration, suggesting its potential role in the tumor microenvironment. In conclusion, GOLT1B promotes CESC progression via interaction with TBK1 and augmentation of NF-κB signaling-mediated cancer-associated inflammation, which provides us with a new approach to CESC target therapy.
Efficient topical treatments of cutaneous lupus erythematosus: a systematic review and network ­meta-analysis
Authors: Fukasawa Takemichi , Yoshizaki-Ogawa Asako , Enomoto Atsushi , Miyagawa Kiyoshi , Sato Shinichi , Yoshizaki Ayumi 
Published: August 2024

Abstract
Although topical agents have been used to treat cutaneous lupus erythematosus (CLE), there was previously no high-quality evidence of which agents were most effective and which clinical scores were most suitable.
On 22 December 2023, a search was conducted across five databases to identify randomized controlled trials (RCTs) for CLE. Two authors independently screened the titles and abstracts of articles based on predetermined criteria. Selected articles were then assessed for inclusion in a blinded manner, with any disagreements resolved through consensus. Data were abstracted in duplicate, and a random-effects model was utilized for network meta-analysis. The certainty of the evidence was evaluated according to the PRISMA guidelines, using the GRADE approach. The analysis was finalized in January 2024, with the primary outcome focused on the change in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) from baseline.
Seven RCTs involving 231 participants were analysed. The network meta-analysis revealed that nicotinamide 4% demonstrated the highest probability of achieving the intended outcomes, with a mean difference (MD) of 3.10 and a 95% confidence interval (CI) of 1.99–4.21. Additionally, clobetasol 0.05%, nicotinamide 2% and tacrolimus 0.1% also exhibited statistically significant differences, with MDs of 2.30 (95% CI of 0.73–3.88), 2.30 (95% CI 0.97–3.63) and 1.30 (95% CI 0.03–2.57), respectively.
This NMA demonstrates with a high level of evidence that nicotinamide 4%, clobetasol 0.05%, nicotinamide 2% and tacrolimus 0.1% are statistically significant topical agents for CLE. CLASI may be an appropriate outcome to evaluate drug efficacy in CLE.
Assessment of clinician-reported outcome measures for alopecia areata: a systematic scoping review
Authors: Darchini-Maragheh Emadodin , Moussa Anthony , Rees Huw , Jones Leslie , Bokhari Laita , Sinclair Rodney 
Published: August 2024

Abstract

Background
Clinician-reported outcome measures (ClinROMs) are an important part of disease assessment in daily practice and clinical trials. There is a broad disagreement on the most appropriate ClinROM for a comprehensive assessment of alopecia areata (AA) severity.

Objectives
To identify the currently available ClinROMs for AA through a systematic literature search, address their practical strengths and weaknesses, and identify the road ahead for future research.

Methods
A search was conducted of the published, peer-reviewed literature via PubMed (MEDLINE) and Embase (via Ovid) databases. Articles published in English within the past 23 years (post-2000) that objectively measured AA severity were included. We did not select scoring systems that were solely based on patient-reported outcomes.

Results
The literature search identified 1376 articles, of which 27 were chosen for full-text review. Based on our eligibility criteria, 14 articles were identified, describing 16 different ClinROMs. Five ClinROMs solely measured scalp hair loss [Severity of Alopecia Tool (SALT), SALT II, Alopecia Density and Extent (ALODEX), pediatric SALT (pSALT) and Alopecia Areata Investigator Global Assessment Scale (AA-IGA)]. Three trichoscopy-based ClinROMs assessed disease activity [Alopecia Areata Progression Index (AAPI), Alopecia Areata Predictive Score (AAPS) and the coudability hair score]. Six ClinROMs exclusively assessed nonscalp areas [Brigham Eyebrow Tool for Alopecia Areata (BETA), Brigham Eyelash Tool for Alopecia Areata (BELA), Alopecia Barbae Severity (ALBAS), ClinRO Measure for Eyebrow Hair Loss™, ClinRO Measure for Eyelash Hair Loss™ and ClinRO Measure for Nail Appearance™]. Two ClinROMs assessed both scalp and nonscalp domains [Alopecia Areata Severity Index (AASI) and Alopecia Areata Scale (AASc)]. The practical strengths and weaknesses of each assessment tool are described.

Conclusions
Various practical limitations associated with their established tools have impeded the universal implementation in routine clinical practice. There is a significant need for a composite clinical severity scoring system to capture all the key severity identifiers beyond the involvement of the scalp.
Immune cell activity during anti-TNF treatment in patients with psoriasis and psoriatic arthritis
Authors: Petrovic Aleksandra , Samuelsen Victoria Marie , Davies Richard , Aarebrot Anders K , Holmes Timothy , Sarkar Irene , Bergum Brith , Jonsson Roland , Sandvik Lene F , Solberg Silje M , Appel Silke 
Published: August 2024

Abstract
Psoriasis is a chronic, inflammatory skin disease characterized by a dysregulated immune response and systemic inflammation. Up to one-third of patients with psoriasis have psoriatic arthritis (PsA). Targeted treatment with antibodies neutralizing tumor necrosis factor can ameliorate both diseases. We here explored the impact of long-term infliximab treatment on the composition and activity status of circulating immune cells involved in chronic skin and joint inflammation. Immune cells were analyzed by multicolor flow cytometry. We measured markers of immune activation in peripheral blood mononuclear cell populations in 24 infliximab-treated patients with psoriasis/PsA compared to 32 healthy controls. We observed a significant decrease in the frequency of both peripheral natural killer (NK) cells and their subset CD56dimCD16+ NK cells in PsA compared to healthy controls and patients with psoriasis. The latter had a strong-positive correlation with psoriasis area severity index (PASI) in these patients, while CD56brightCD16− NK cells were negatively correlated with PASI. In addition, we observed an upregulation of CD69+ intermediate CD14+CD16+ and CD69+ classical CD14+CD16− monocytes in PsA and increased activity of CD38+ intermediate CD14+CD16+ monocytes in patients with psoriasis. Compared to healthy controls, psoriasis patients demonstrated shifts of the three B-cell subsets with a decrease in transitional CD27-CD38high B cells. Our exploratory study indicates a preserved pathophysiological process including continuous systemic inflammation despite clinical stability of the patients treated with infliximab.
Circulating neutrophil extracellular trap-forming neutrophils in rheumatoid arthritis exacerbation are majority dual endothelin-1/signal peptide receptor+ subtype
Authors: Cross Andrew L , Wright Helen L , Choi Jacqueline , Edwards Steven W , Ruiz-Opazo Nelson , Herrera Victoria L M 
Published: August 2024

Abstract
Neutrophil extracellular traps (NETs) are associated with rheumatoid arthritis pathogenesis and severity. Since homeostatic NET-forming neutrophils [NET+Ns] have beneficial roles in defense against pathogens, their distinction from pro-injury [NET+N] subtypes is important, especially if they are to be therapeutically targeted. Having identified circulating, pro-injury DEspR+CD11b+[NET+Ns] in patients with neutrophilic secondary tissue injury, we determined whether DEspR+[NET+Ns] are present in rheumatoid arthritis (RA) flares. Whole blood samples of patients with RA flares on maintenance therapy (n = 6) were analyzed by flow cytometry (FCM) and immunofluorescence cytology followed by semi-automated quantitative confocal microscopy (qIFC). We assessed clinical parameters, levels of neutrophils and [NET+Ns], and plasma S100A8/A9. qIFC detected circulating DEspR+CD11b+neutrophils and [NET+Ns] in RA-flare patients but not healthy controls. DEspR+[NET+Ns] were positive for citrullinated histone H3 (citH3+), extruded DNA, decondensed but recognizable polymorphic nuclei, and [NET+N] doublet interactions in mostly non-ruptured NET-forming neutrophils. Circulating DNA+/DEspR+/CD11b+/citH3+microvesicles (netMVs) were observed. FCM detected increased %DEspR+CD11b+neutrophils and DEspR+ cell–cell doublets whose levels trended with DAS28 scores, as did plasma S100A8/A9 levels. This study identifies circulating DEspR+/CD11b+neutrophils and [NET+Ns] in RA-flare patients on maintenance therapy. Detection of circulating DEspR+citH3+[NET+Ns] and netMVs indicate a systemic neutrophilic source of citH3-antigen concordant with multi-joint RA pathogenesis. Increased S100A8/A9 alarmin levels are associated with cell injury and released upon NET-formation. As a ligand for TLR4, S100A8/A9 forms a positive feedback loop for TLR4-induced DEspR+neutrophils. These data identify DEspR+neutrophils and [NET+Ns] in RA pathogenesis as a potential biomarker and/or therapeutic target.
The proactive and reactive mechanisms of learned spatial suppression
Authors: Zhao Guang , Chen Jiahuan , Duan Yuhao , Li Shiyi , Wang Qiang , Li Dongwei 
Published: August 2024

Abstract
Selection history refers to the notion that previous allocations of attention or suppression have the potential to elicit lingering and enduring selection biases that are isolated from goal-driven or stimulus-driven attention. However, in the singleton detection mode task, manipulating the selection history of distractors cannot give rise to pure proactive inhibition. Therefore, we employed a combination of a working memory task and a feature search mode task, simultaneously recording cortical activity using EEG, to investigate the mechanisms of suppression guided by selection history. The results from event-related potential and reaction times showed an enhanced inhibitory performance when the distractor was presented at the high-probability location, along with instances where the target appeared at the high-probability location of distractors. These findings demonstrate that a generalized proactive inhibition bias is learned and processed independent of cognitive resources, which is supported by selection history. In contrast, reactive rejection toward the low-probability location was evident through the Pd component under varying cognitive resource conditions. Taken together, our findings indicated that participants learned proactive inhibition when the distractor was at the high-probability location, whereas reactive rejection was involved at low-probability location.
Development of diazirine–alkyne tag for protein–ligand interaction analysis with photoaffinity labeling
Authors: Nakatani Masatoshi , Ebihara Shohei , Kita Masaki 
Published: August 2024

Abstract
We have developed a diazirine–alkyne tag for target protein–ligand interaction analysis. A sulfonamide photoaffinity probe was readily prepared using copper-catalyzed azide–alkyne cycloaddition (CuAAC), which site-specifically formed a covalent bond with human carbonic anhydrase 1 (∼30% labeling yield). The photolabeled position (E58–H64 region) was determined based on the results of a tandem mass spectrometry (MS/MS) analysis of tryptic peptides and was supported by molecular modeling studies. Our method may be useful for determining unknown ligand-binding sites of various target biomolecules.
Sudden unexpected death in epilepsy: respiratory vs. cardiac contributions
Authors: Lin Susan , Schwartz Theodore H , Pitt Geoffrey S 
Published: August 2024

Abstract
Sudden unexpected death in epilepsy (SUDEP) poses a significant risk to life expectancy for individuals with epilepsy. Mechanistic insight, while incomplete, has advanced through clinical observational studies and animal models. Yet we lack preventative therapies, which will depend on understanding SUDEP mechanisms. Recurrent convulsive seizures are the major SUDEP risk factor. Cardiorespiratory dysfunction precedes SUDEP, but whether cardiac arrhythmias are major proximate culprits for SUDEP remains to be determined. Here, we highlight recent data from mouse models and clinical studies that provide increasing support for respiratory depression and decreasing evidence for tachyarrhythmia-induced SUDEP. Further, we review data from genetic and chemoconvulsant mouse models that have enabled a deeper understanding for how seizures initiated in the central nervous system propagate to the autonomic nervous system and drive seizure-induced respiratory depression and subsequent SUDEP, rather than supporting a proximate cardiac arrhythmia cause. Ongoing research will continue to identify predictive SUDEP biomarkers, improve animal models, and translate basic research into precision medicine approaches. Identifying and understanding the brainstem circuits vulnerable in seizure-induced apnoea will enable therapeutic interventions to enhance the quality of life and life expectancy for individuals with epilepsy.
Strength of parrot flight feathers is a function of position on the wing
Authors: Deeming Denis Charles , Hutchings Connor J , Seaward Fern G , Goodman Adrian M 
Published: August 2024

Abstract
Powered flight in birds is reliant on feathers forming an aerodynamic surface that resists air pressures. Many basic aspects of feather functionality are unknown, which hampers our understanding of wing function in birds. This study measured the dimensions of primary and secondary flight feathers of 19 species of parrots. The maximum force the feathers could withstand from below was also measured to mimic the pressures experienced during a downstroke. The analysis tested whether: (1) feather dimensions differed along the wing and among secondary and primary remiges; (2) the force that feathers could withstand varied among the remiges; and (3) there would be isometric relationships with body mass for feather characteristics. The results show that body mass significantly affected vane width, rachis thickness, maximum force, and ultimate bending moment, but the relationship for feather length only approached significance. Many of the proximal secondary feathers showed significantly lower values relative to the first primary, whereas for distal primaries the values were greater. There were isometric relationships for force measurements of primary and secondary feathers with body mass, but there was positive allometry for feather lengths and vane widths. The forces feathers can withstand vary along the wing may be a proxy for the aerodynamic properties of the feathers in situ. Broader taxonomic studies that explore these topics are required for other species representing a range of different orders. A better understanding of the functionality of feathers will improve our understanding of how avian flight works particularly considering the variety in flight style and wing shape in birds.
Esophagectomy after definitive chemoradiation in esophageal cancer: a safe therapeutic strategy
Authors: van Geffen Eline G M , Neelis Karen J , Putter Hein , Slingerland Marije , de Steur Wobbe O , van der Kraan Jolein , van der Molen Aart J , Crobach A Stijn L P , Hartgrink Henk H 
Published: August 2024

Summary
The standard treatment regimen for esophageal cancer is chemoradiation followed by esophagectomy. However, the use of neoadjuvant chemoradiotherapy damages the surrounding tissue, which potentially increases the risk of postoperative complications, including anastomotic leakage. The impact of definitive chemoradiotherapy (dCRT, 50.4 Gy radiotherapy) compared to the standard neoadjuvant scheme (nCRT, 41.4 Gy radiotherapy) prior to surgery on the incidence of anastomotic leakage remains poorly understood. To study this, all patients who received dCRT between 2011 and 2021 followed by esophagectomy were included. For each patient, two patients who received nCRT were selected as matched controls. Outcomes included postoperative anastomotic leakage, pulmonary and other complications, anastomotic stenosis, pulmonary and other postoperative complications (Clavien Dindo Classification ≥1), and overall survival. One hundred and eight patients were included with a median follow-up of 28 months. The time between neoadjuvant treatment and surgery was longer in the dCRT group compared to the nCRT group (65 vs. 48 days, P &lt; 0.001). Postoperatively, significantly more patients in the dCRT group suffered from anastomotic leakage (11% vs. 1%, P = 0.04) and anastomotic stenosis (42% vs. 17%, P &lt; 0.01). No differences were found for other complications or overall survival between both groups. In conclusion, preoperative dCRT is associated with a higher risk of anastomotic leakage and stenosis. These complications, however, can be treated effectively. Therefore, esophagectomy after dCRT is considered to be an appropriate treatment strategy in a selected patient group.