julilili42/papers huggingface dataset:
Slack potassium channels in spinal dorsal horn neurons control neuropathic pain and acute itch
2024-10-08

Abstract The sodium-activated potassium channel Slack (K Na 1.1, Kcnt1) plays a critical role in tuning neuronal excitability. Previous studies have revealed that Slack is expressed in neurons of the superficial dorsal horn of the spinal cord. However, the precise role of Slack in spinal dorsal horn neurons is unclear. In this study, we used mice in which Slack is conditionally ablated in spinal dorsal horn neurons (Lbx1-Slack −/− mice) and analyzed their behaviors in various models of pain and itch. Lbx1-Slack −/− mice exhibited increased neuropathic pain behavior after peripheral nerve injury but normal responses in a model of inflammatory pain. Unexpectedly, Lbx1-Slack −/− mice demonstrated increased scratching after intradermal injection of chloroquine, LY344864, and histamine. Moreover, neuromedin B receptors are coexpressed with Slack in the dorsal horn, and scratching after intrathecal delivery of neuromedin B was increased in Lbx1-Slack −/− mice. Our study provides in vivo evidence that Slack expressed in spinal dorsal horn neurons inhibits nerve injury–induced allodynia and acute itch induced by various pruritogens.
Factors Influencing Background Parenchymal Enhancement in Contrast-Enhanced Mammography Images
2024-10-08

Background: The aim of this study is to evaluate the correlation between background parenchymal enhancement (BPE) and various patient-related and technical factors in recombined contrast-enhanced spectral mammography (CESM) images. Material and Methods: We assessed CESM images from 62 female patients who underwent CESM between May 2017 and October 2019, focusing on factors influencing BPE. A total of 235 images, all acquired using the same mammography machine, were analyzed. A region of interest (ROI) with a standard size of 0.75 to 1 cm2 was used to evaluate the minimal, maximal, and average pixel intensity enhancement. Additionally, the images were qualitatively assessed on a scale from 1 (minimal BPE) to 4 (marked BPE). We examined correlations with body mass index (BMI), age, hematocrit, hemoglobin levels, cardiovascular conditions, and the amount of pressure applied during the examination. Results: Our study identified a significant correlation between the amount of pressure applied during the examination and the BPE (Spearman’s ρ = 0.546). Additionally, a significant but weak correlation was observed between BPE and BMI (Spearman’s ρ = 0.421). No significant associations were found between BPE and menopausal status, cardiovascular preconditions, hematocrit, hemoglobin levels, breast density, or age. Conclusions: Patient-related and procedural factors significantly influence BPE in CESM images. Specifically, increased applied pressure and BMI are associated with higher BPE.
Collagen fleece grafting for surgical treatment of patients with mild to severe peyronie’s curvatures
2024-10-08

Abstract Purpose Collagen fleece grafting (CFG) is the recommended treatment for severe Peyronie’s disease (PD) curvature (&gt; 60°), but its efficacy in mild/moderate curvatures remains uncertain. This study evaluated CFG in patients with mild/moderate curvatures (&lt; 60°) at risk of penile shortening or symptomatic plaque. Methods A retrospective review was conducted on patients who underwent surgical treatment for PD using plaque incision or partial plaque excision and CFG. Clinical parameters and complications were reviewed. Subgroup analysis was performed on patients with curvatures of &gt; 60° and curvatures ≤ 60°. Results 89 patients with a median age of 59 years and a median curvature of 70 (20–90)° were identified. Dorsal curvature was predominant in 66% of cases, followed by lateral (16%), ventral (8%), and complex curvatures (10%). Partial plaque excision was performed in 98% of patients, with an average grafting area of 2.1 cm 2 ; 71% had a singular penile plaque, while 29% presented two or more plaques. The comparison between patients with curvatures ≤ 60° and &gt; 60° revealed no significant differences in mean operation time (86.3 vs. 94.4 min, p = 0.13) or in the incidence of postoperative complications, including glans necrosis, hypoesthesia, ecchymosis, bleeding, hematoma, infection, residual curvature, revision surgery, or pain. Conclusions Early postoperative outcomes and complication rates following plaque incision or partial plaque excision and grafting with CFG were comparable in patients with mild/moderate and severe PD deformities. The technique may be a viable option with a similar risk profile for achieving penile straightening in selected PD cases, particularly when plication is not feasible.
Exploring print media coverage of elite athletes’ mental illness between 2010 and 2023 in Germany: a quantitative content analysis
2024-10-08

Objectives Recently, the stereotype of elite athletes' invulnerabilty has begun to be challenged by an increasing number of elite athletes who talk openly about struggling with mental health. Relatedly, previous research has focused primarily on specific incidents like the media's portrayal of personal disclosures. The purpose of this study was to expand this perspective and give a systematic overview of media coverage related to elite athletes' mental illness by examining more than one decade (2010–2023) of German print media reporting. Specifically, we were interested in changes over time and between broadsheet and tabloid press regarding content-related and formal aspects. Methods Based on a systematic search and screening process in eleven German newspapers and magazines, 699 print media articles were analyzed with a codebook, forming a framework of content-related (reported mental disorder; central thematic focus; sources of comments and quotations; perspectives on the high-performance sports system) and formal categories (article genre; elements of responsible journalism). Univariate analyses and binary logistic regression models were used to examine changes over time (2010–2016 vs. 2017–2023) and differences between types of press (tabloid vs. broadsheet press) regarding content-related and formal characteristics. Results The results indicate an enhanced awareness towards the topic of mental illness and those affected in recent years within German print media. This was demonstrated by the increased integration of responsible reporting elements, the inclusion of diversified perspectives and the considerate selection of content. Despite this positive trend over time, the findings also suggest that media reporting in the tabloid press bears an increased risk for inappropriate storytelling, focusing primarily on personal tragedies. Conclusion As personal fate of prominent figures like elite athletes will always meet great interest in the public, it is of utmost importance that the media report responsibly and promote critical thinking in society. The study shows the media's willingness to question conventional ideals embedded in the sports culture and take a more critical approach to the topic of mental illness in high-performance sports. By demonstrating a greater understanding of the importance and the seriousness of the issue, the media might also contribute to improved mental health awareness in society.
Angioinvasive Rhino-Orbital-Cerebral Mucormycosis in a Patient with Type 2 Diabetes Mellitus: A Complex and Lethal Cause of Stroke
2024-10-08

Rhino-orbital-cerebral mucormycosis is a rapidly progressive and often fatal fungal infection caused by molds of the order Mucorales, particularly affecting immunocompromised individuals. This infection is notorious for its angioinvasive properties, enabling the fungi to invade blood vessels and leading to tissue necrosis. We report the clinical course of a 59-year-old Caucasian man with poorly controlled type 2 diabetes (HbA1c 16.8%) who presented with unilateral headache, left-sided facial numbness, and incomplete left ocular motor paresis. Initial presentation raised suspicion of orbital phlegmon, leading to antibiotic and later corticosteroid pulse therapy, which worsened the patient’s condition. Subsequent imaging demonstrated extensive inflammatory changes, including wall irregularities of the left intracranial internal carotid artery, accompanied by ocular protrusion and periorbital enhancement. New palatal lesions indicated mucormycosis, which was confirmed by molecular analysis of a palatal biopsy, leading to Amphotericin B treatment. Pre-surgery imaging revealed a malignant middle cerebral artery infarction, and the patient died 16 days after symptom onset and 12 days after initial presentation under palliative care due to a poor prognosis. This case of angioinvasive mucormycosis underscores the severe and often fatal course of rhino-orbital-cerebral mucormycosis in an immunocompromised individual. The rapid progression from initially vague and unspecific symptoms to extensive vascular involvement and stroke highlights the critical need for early and accurate diagnosis, as well as prompt intervention to prevent further disease progression. Additionally, this case also illustrates the potential risks associated with corticosteroid therapy in the presence of undiagnosed fungal infections, which can exacerbate the condition and lead to serious complications. Clinicians should maintain a high index of suspicion for mucormycosis in similar clinical scenarios, prioritizing adequate antifungal treatment and careful monitoring to improve patient outcomes. Early interdisciplinary collaboration is essential for the effective management of such complex cases.
Examining Multiculturals’ and Multilinguals’ Paradoxical Bridging Behaviors in Overcoming Cultural and Language Barriers in Organizations
2024-10-08

Research has identified the usefulness of multicultural and multilingual employees in overcoming cultural and language barriers in international work contexts, but still needs to clarify why and how these employees engage in bridging behavior. Based on in-depth analyses of 154 interviews, we inductively develop a comprehensive model of bridging behaviors with novel and counterintuitive insights. We show that bridging behaviors are not only based on individual strengths, which multiculturals and multilinguals possess, but also—paradoxically—on their weaknesses. Multiculturals’ and multilinguals’ strengths and experience with weaknesses result in different determinants and enactments of bridging. Grounded in our inductive theory building, we propose four bridging behaviors: cultural teaching, language teaching, cultural facilitating, and language facilitating. Multiculturals and multilinguals cycle between these bridging behaviors depending on their capabilities and motivations in specific situations. We provide theoretical and practical implications of our findings.
Tumour-informed liquid biopsies to monitor advanced melanoma patients under immune checkpoint inhibition
2024-10-09

Abstract Immune checkpoint inhibitors (ICI) have significantly improved overall survival in melanoma patients. However, 60% experience severe adverse events and early response markers are lacking. Circulating tumour DNA (ctDNA) is a promising biomarker for treatment-response and recurrence detection. The prospective PET/LIT study included 104 patients with palliative combined or adjuvant ICI. Tumour-informed sequencing panels to monitor 30 patient-specific variants were designed and 321 liquid biopsies of 87 patients sequenced. Mean sequencing depth after deduplication using UMIs was 6000x and the error rate of UMI-corrected reads was 2.47×10 −4 . Variant allele fractions correlated with PET/CT MTV (rho=0.69), S100 (rho=0.72), and LDH (rho=0.54). A decrease of allele fractions between T1 and T2 was associated with improved PFS and OS in the palliative cohort (p = 0.008 and p &lt; 0.001). ctDNA was detected in 76.9% of adjuvant patients with relapse (n = 10/13), while all patients without progression (n = 9) remained ctDNA negative. Tumour-informed liquid biopsies are a reliable tool for monitoring treatment response and early relapse in melanoma patients with ICI.
Next-to-Next-to-Leading Order Global Analysis of Polarized Parton Distribution Functions
2024-10-09

We present a next-to-next-to-leading order (NNLO) global QCD analysis of the proton’s helicity parton distribution functions, the first of its kind. To obtain the distributions, we use data for longitudinal spin asymmetries in inclusive and semi-inclusive lepton-nucleon scattering as well as in weak-boson and hadron or jet production in proton-proton scattering. We analyze the data using QCD perturbation theory at NNLO accuracy, employing approximations provided by the threshold resummation formalism in cases where full NNLO results for partonic hard-scattering functions are not readily available. Our numerical results suggest a remarkable perturbative stability of the extracted helicity parton distribution functions. Published by the American Physical Society 2024
Involvement of muscarinic acetylcholine receptor-mediated cholinergic neurotransmission in TMS–EEG responses
2024-10-09

The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) is emerging as a valuable tool for investigating brain functions in health and disease. However, the detailed neural mechanisms underlying TMS-EEG responses, including TMS-evoked EEG potentials (TEPs) and TMS-induced EEG oscillations (TIOs), remain largely unknown. Combining TMS-EEG with pharmacological interventions provides a unique opportunity to elucidate the roles of specific receptor-mediated neurotransmissions in these responses. Here, we investigated the involvement of muscarinic acetylcholine receptor (mAChR)-mediated cholinergic neurotransmission in TMS-EEG responses by evaluating the effects of mAChR antagonists on TEPs and TIOs in twenty-four healthy participants using a randomized, placebo-controlled crossover design. TEPs and TIOs were measured before and after administering a single oral dose of scopolamine (a non-selective mAChR antagonist), biperiden (an M1 mAChR antagonist), or placebo, with TMS targeting the left medial prefrontal cortex (mPFC), angular gyrus (AG), and supplementary motor area (SMA). The results indicated that mAChR-mediated cholinergic neurotransmission played a role in TEPs, but not TIOs, in a target-specific manner. Specifically, scopolamine significantly increased the amplitude of a local TEP component between approximately 40 and 63 ms post-stimulus when TMS was applied to the SMA, but not the mPFC or AG. Biperiden produced a similar but less pronounced effect. Importantly, the effects of these mAChR antagonists on TEPs were independent of those on sensory-evoked EEG potentials caused by TMS-associated sensory stimulation. These findings expand our understanding of TMS-EEG physiology, providing insights for its application in physiological and clinical research.
Networks of Supply and Elite Consumers in England and Germany, c. 1750–1830
2024-10-09

Abstract This comparative study explores the consumption practices and systems of supply of elite families in England and Germany from the middle of the eighteenth into the early nineteenth century. The paper focuses on three key elements of elite consumption – silverware, livery, and wine – to tease out important aspects of the elite’s use of consumer goods as a means of self-expression and for the construction of status. The study identifies important differences as well as similarities between English and German retail systems and in doing so further questions the notion of a single model of retail development: Germany was not a stage behind England on a linear development trajectory, but was instead characterised by a dispersed yet integrated system of retail centres. The complex interplay of local, regional and national systems of supply highlighted in this study has implications far beyond these elite families and invites a reassessment of the prevalent notions of consumption history.
Compound Heterozygous RYR1 Variants in a Patient with Severe Congenital Myopathy: Case Report and Comparison with Additional Cases of Recessive RYR1-Related Myopathy
2024-10-09

Pathogenic variants in the ryanodine receptor 1 (RYR1) gene are causative for a wide spectrum of muscular phenotypes, ranging from malignant hyperthermia over mild, non-progressive to severe congenital myopathy. Both autosomal dominant and recessive inheritance can occur, with the more severe forms usually showing recessive inheritance. However, genotype–phenotype correlations are complicated due to the large size of the gene and heterogeneous phenotypes. We present a 6-year-old patient with severe congenital myopathy, carrying a heterozygous pathogenic RYR1 variant inherited from the healthy mother. Through whole genome sequencing we identified a second, deep intronic RYR1 variant that has recently been described in another patient with severe congenital myopathy and shown to affect splicing. Segregation analyses confirmed the variants to be compound heterozygous. We compared our patient’s phenotype to that of the patient from the literature as well as five additional patients with compound heterozygous RYR1 variants from our center. The main overlapping features comprised congenital onset, predominant muscular hypotonia, and normal creatine kinase (CK) levels, while overall clinical expression varied substantially. Interestingly, both patients carrying the new intronic splice variant showed a very severe disease course. More widespread use of genome sequencing will open the way for better genotype–phenotype correlations.
Altered thymic niche synergistically drives the massive proliferation of malignant thymocytes
2024-10-09

The discovery of genetic alterations in patient samples over the last decades has reinforced a cell-autonomous view of proliferative expansion during T-cell acute lymphoblastic leukemia (T-ALL) development in the thymus. However, the potential contribution of non-cell-autonomous factors, particularly the impact of thymic epithelial cells (TECs) within the thymic niche during the initiation phase, remains unexplored. In this study, we combine a cell-based computational model of the thymus with complementary in vivo experiments in medaka ( Oryzias latipes ) to systematically analyze the impact of 12 cell-autonomous and non-autonomous factors, individually and in combination, on the proliferation of normal and malignant thymocytes carrying interleukin-7 receptor (IL7R) gain-of-function mutations or elevated IL7R levels, as observed in T-ALL patients. By simulating over 1500 scenarios, we show that while a dense TEC network favored the proliferation of normal thymocytes, it inhibited the proliferation of malignant lineages, which achieved their maximal proliferative capacity when TECs were sparsely distributed. Our in silico model further predicts that specific mutations could accelerate proliferative expansion within a few days. This prediction was experimentally validated, revealing the rapid onset of thymic lymphoma and systemic infiltration of malignant T cells within just 8 days of embryonic development. These findings demonstrate that synergistic interaction between oncogenic alterations and modifications in the thymic niche can significantly accelerate disease progression. Our results also suggest that negative feedback from the proliferative state suppresses thymocyte differentiation. Overall, this multidisciplinary work reveals the critical role of TEC-thymocyte interactions in both the initiation and progression of T-ALL, highlighting the importance of the thymic microenvironment in early leukemogenesis.
Altered thymic niche synergistically drives the massive proliferation of malignant thymocytes
2024-10-09

Abstract The discovery of genetic alterations in patient samples over the last 20 years has promoted a cell-autonomous view of proliferative expansion during T-cell acute lymphoblastic leukemia (T-ALL) development in the thymus. However, the potential contribution of non-cell-autonomous factors, particularly the impact of thymic epithelial cells (TECs) within the thymic niche during the initiation phase, remains unexplored. In this study, we employ a unique combination of a cell-based computational model of the thymus and in vivo experiments. We systematically analyze the impact of 12 cell-autonomous and non-autonomous factors, either alone or in combinations, on the proliferation of normal and malignant thymocytes with interleukin-7 receptor (IL7R) gain-of-function mutations or elevated IL7R levels, as observed in T-ALL patients. By simulating over 1500 scenarios, we show that while a dense TEC network favored the proliferation of normal thymocytes, it inhibited the proliferation of malignant lineages, which achieved their maximal proliferative capacity when TECs were sparsely distributed. Our in silico model predicts that certain mutations could accelerate proliferative expansion within a few days. This was experimentally validated, revealing rapid onset of thymus lymphoma and infiltration of malignant T-cells into other organs within 8 days of medaka (Oryzias latipes) embryonic development, thus revealing that modifications in the thymic niche and oncogenes in thymocytes together accelerate the disease development. Our results also suggest that negative feedback from the proliferative state inhibits differentiation of thymocytes, thereby prolonging the proliferative state and further fueling malignant expansion. Overall, this work reveals the critical impact of TEC-thymocyte interactions in both the initiation and progression of disease.