julilili42/papers huggingface dataset:
Central Nervous System Involvement and Neuroradiological Imaging Insights of Neurocutaneous Melanocytosis in Congenital Melanocytic Nevi
2024-10-22

Congenital melanocytic nevi (CMN) are pigmented lesions present at birth, varying widely in size and clinical impact. In rare instances, these nevi become visible during the first months of life, a phenomenon known as tardive melanocytic nevi (tardive CMN). Giant congenital melanocytic nevi (GCMN) are defined as nevi larger than 40 cm in projected adult size (PAS). Their association with the central nervous system (CNS) poses significant risks, including melanoma and neurocutaneous melanocytosis (NCM), where melanocytes infiltrate the CNS, potentially causing seizures, hydrocephalus, and, rarely, CNS melanoma. MRI is recommended for GCMN patients, particularly those with numerous satellite nevi or neurological symptoms, to detect CNS involvement. The Nevosurgery Network recommends MRI examinations in cases of GCMN (&gt;40 cm PAS), the presence of over 20 concomitant nevi, and neurological symptoms requiring clarification. CMN can be associated with melanocyte accumulations and melanin deposits in the brain, spinal cord, and leptomeninges.
Piercing the Mystery: Predator Identification Using the Perforated Tests of the Sea Urchin Brissus unicolor (Leske, 1778)
2024-10-22

ABSTRACT Drilling predation on echinoids (sea urchins) has been known to occur in marine ecosystems since the Jurassic Period; however, it has rarely been studied in existing species. Tests of the irregular sea urchin Brissus unicolor (Leske, 1778), which frequently occurs in shallow substrates of the Canary Islands, mostly show very evident perforations through their skeletons. The aim of this study was to describe the characteristics of these perforations in order to determine their possible origins as well as document their size, site selectivity, and frequency of occurrence among different sample sites. Of the 104 tests of B . unicolor that were collected from 15 locations off the island of Tenerife (Canary Islands, Spain), 94% showed a least one perforation. These boreholes exhibit a circular morphology, penetrating the sea urchin tests perpendicularly and entirely. Notably, they display a unique acid signature, diverging from those documented in the fossil record and other relevant studies. Our analysis showed size and site selectivity by the predator as the perforations were mainly located on the oral side of the test. The perforations are attributed to drilling predation. The characteristics of these boreholes on B . unicolor match published records of predation marks suggesting that they are produced by the predatory gastropod family Cassidae, with Semicassis undulata (Gmelin, 1791) considered to be the most probable predator.
Antibiotic-induced loss of gut microbiome metabolic output correlates with clinical responses to CAR T-cell therapy
2024-10-23

Abstract Antibiotic (ABX)–induced microbiome dysbiosis is widespread in oncology, adversely affecting outcomes and side effects of various cancer treatments, including immune checkpoint inhibitors and chimeric antigen receptor T-cell (CAR-T) therapies. In this study, we observed that prior exposure to broad-spectrum ABXs with extended anaerobic coverage such as piperacillin-tazobactam and meropenem was associated with worse anti-CD19 CAR-T therapy survival outcomes in patients with large B-cell lymphoma (N = 422) than other ABX classes. In a discovery subset of these patients (n = 67), we found that the use of these ABXs was in turn associated with substantial dysbiosis of gut microbiome function, resulting in significant alterations of the gut and blood metabolome, including microbial effectors such as short-chain fatty acids (SCFAs) and other anionic metabolites, findings that were largely reproduced in an external validation cohort (n = 58). Broader evaluation of circulating microbial metabolites revealed reductions in indole and cresol derivatives, as well as trimethylamine N-oxide, in patients who received ABX treatment (discovery, n = 40; validation, n = 28). These findings were recapitulated in an immune-competent CAR-T mouse model, in which meropenem-induced dysbiosis led to a systemic dysmetabolome and decreased murine anti-CD19 CAR-T efficacy. Furthermore, we demonstrate that SCFAs can enhance the metabolic fitness of CAR-Ts, leading to improved tumor killing capacity. Together, these results suggest that broad-spectrum ABX deplete metabolically active commensals whose metabolites are essential for enhancing CAR-T efficacy, shedding light on the intricate relationship between ABX exposure, microbiome function and their impact on CAR-T efficacy. This highlights the potential for modulating the microbiome to augment CAR-T immunotherapy. This trial was registered at www.clinicaltrials.gov as #NCT06218602.
Climatic and environmental changes of ~100 thousand years: The mammals from the early Middle Pleistocene sequence of Notarchirico (southern Italy)
2024-10-23

Here we revise all the paleontological sample of Notarchirico, including historical collections and new findings collected during 2016–2023 excavations. Notarchirico is one of the most significant sites for the study of human evolution and terrestrial ecosystem dynamics during the Early-Middle Pleistocene Transition, preserving nearly 100.000 years of environmental and climatic changes constrained between 695 ± 6 ka and 614 ± 12 ka. The deposit yielded the oldest human fossil of the Italian Peninsula, and one of the oldest European evidence of Homo heidelbergensis , as well as one of the earliest evidence of bifacial tools in western Europe, commonly associated with the Acheulean techno-complex. Our paleontological results revealed the presence of three different mammal complexes, documenting faunal dynamics in response of climatic driven-changes recognized during the early Middle Pleistocene. The lower complex (levels I2-G) indicates the dominance of wooded spaces, sparse steppes, and the existence of water bodies (lakes or ponds), indicating a deterioration of the fully interglacial conditions recorded during the end of MIS 17; the middle complex (levels G-C) with a low number of mammal remains can be attributed to the glacial conditions of MIS 16; the upper complex (levels B-above α) indicates an improvement in climate, transitioning towards the full interglacial conditions of the of MIS 15. The faunal sample of Notarchirico, based on its firm chronological setting, offers important data for the Biochronological Scheme of European Land Mammals, including one of the oldest records of Palaeoloxodon antiquus and Cervus elaphus in Europe, Panthera spelaea in southwestern Europe, Dama cf. roberti in Italian Peninsula, and one of the latest occurrences of Bison schoetensacki in Europe.
Transverse momentum dependence of the T-even hadronic structure functions in the Drell-Yan process
2024-10-23

We present detailed analysis of the <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" display="inline"><a:mi>T</a:mi></a:math>-even lepton angular distribution in the Drell-Yan process including <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" display="inline"><c:mi>γ</c:mi><c:mo>/</c:mo><c:msup><c:mi>Z</c:mi><c:mn>0</c:mn></c:msup></c:math> gauge boson exchange and using perturbative QCD based on the collinear factorization scheme at leading order in the <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" display="inline"><e:msub><e:mi>α</e:mi><e:mi>s</e:mi></e:msub></e:math> expansion. We focus on the study of the transverse momentum <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" display="inline"><g:msub><g:mi>Q</g:mi><g:mi>T</g:mi></g:msub></g:math> dependence of the corresponding hadronic structure functions and angular coefficients up to next-to-next-to-leading order in the <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" display="inline"><i:msubsup><i:mi>Q</i:mi><i:mi>T</i:mi><i:mn>2</i:mn></i:msubsup><i:mo>/</i:mo><i:msup><i:mi>Q</i:mi><i:mn>2</i:mn></i:msup></i:math> expansion. We analyze <k:math xmlns:k="http://www.w3.org/1998/Math/MathML" display="inline"><k:msub><k:mi>Q</k:mi><k:mi>T</k:mi></k:msub></k:math> dependence numerically and compare <m:math xmlns:m="http://www.w3.org/1998/Math/MathML" display="inline"><m:mi>T</m:mi></m:math>-even angular coefficients integrated over rapidity with available data of the ATLAS Collaboration at LHC. Additionally, we present our results for the forward-backward asymmetry and compare it with data. Published by the American Physical Society 2024
Screen Time, Nature, and Development: Baseline of the Randomized Controlled Study “Screen‐free till 3”
2024-10-23

ABSTRACT In the first years of life, increased screen media use is presumably associated with health consequences and developmental impairments. “Screen‐free till 3” is a prospective Germany‐wide randomized intervention study, started in May 2022 with a duration of 3 years. In the intervention group, 2581 pediatric practices received stickers, which were systematically placed in the screening booklet of all children, along with advice to parents to keep children free from screens until the age of 3. A volunteer sample of 17,436 parents received an invitation to take part in the preinterventional questionnaire. The outcomes were parents' internet use (CIUS test), parental screen time in the presence of children, time of screen media in the background, and children's development. Four thousand twenty‐one parents answered the questionnaire. 16.7% of mothers and 31.0% of fathers reached the CIUS score of an internet‐related disorder. Parents whose children use screen media at an early age had significantly higher CIUS values on average ( M = 4.07) than the parents of children who do not yet have any screen time ( p &lt; 0.001). Combined developmental characteristics show a negative correlation with parental screen time ( p &lt; 0.001). Time spent in nature was positively associated with development ( p &lt; 0.001). The evaluation of the survey shows that screen media is to a large extent used on a daily basis. The study confirms the assumption that high screen media use by parents is linked to higher screen media use by children and also has a negative impact on child development. Trial Registration : Number: RKS00032258; https://drks.de/search/en/trial/DRKS00032258
Identification of novel 3D-genome altering and complex structural variants underlying retinitis pigmentosa type 17 through a multistep and high-throughput approach
2024-10-23

Introduction Autosomal dominant retinitis pigmentosa type 17 (adRP, type RP17) is caused by complex structural variants (SVs) affecting a locus on chromosome 17 (chr17q22). The SVs disrupt the 3D regulatory landscape by altering the topologically associating domain (TAD) structure of the locus, creating novel TAD structures (neo-TADs) and ectopic enhancer-gene contacts. Currently, screening for RP17-associated SVs is not included in routine diagnostics given the complexity of the variants and a lack of cost-effective detection methods. The aim of this study was to accurately detect novel RP17-SVs by establishing a systematic and efficient workflow. Methods Genetically unexplained probands diagnosed with adRP (n = 509) from an international cohort were screened using a smMIPs or genomic qPCR-based approach tailored for the RP17 locus. Suspected copy number changes were validated using high-density SNP-array genotyping, and SV breakpoint characterization was performed by mutation-specific breakpoint PCR, genome sequencing and, if required, optical genome mapping. In silico modeling of novel SVs was performed to predict the formation of neo-TADs and whether ectopic contacts between the retinal enhancers and the GDPD1 -promoter could be formed. Results Using this workflow, potential RP17-SVs were detected in eight probands of which seven were confirmed. Two novel SVs were identified that are predicted to cause TAD rearrangement and retinal enhancer- GDPD1 contact, one from Germany (DE-SV9) and three with the same SV from the United States (US-SV10). Previously reported RP17-SVs were also identified in three Australian probands, one with UK-SV2 and two with SA-SV3. Discussion In summary, we describe a validated multi-step pipeline for reliable and efficient RP17-SV discovery and expand the range of disease-associated SVs. Based on these data, RP17-SVs can be considered a frequent cause of adRP which warrants the inclusion of RP17-screening as a standard diagnostic test for this disease.
Safety evaluations for transtympanic laser stimulation of the cochlea in Mongolian gerbils (Meriones unguiculatus)
2024-10-23

Infrared laser stimulation of the cochlea has been proposed as a possible alternative to conventional auditory prostheses. Whereas previous studies have focused primarily on the short-term effects of laser stimulation, the practical application of this technics requires an investigation into whether prolonged laser exposure can induce neural responses and safely. This study assessed the effect of laser-induced damage to the cochlea on auditory perception using Mongolian gerbils (Meriones unguiculatus) trained with a classical conditioning task. The broadband noise was presented as a conditioned stimulus, and reward licking was recorded as a conditioned response. After training, the subject's cochlea was exposed to a continuous pulsed laser for 15 h. Broadband noise of various intensities was presented without pairing it with water before and after laser exposure to assess the decrease in auditory perception due to laser-induced injury. The licking rate did not change after laser exposure of 6.6 W/cm<sup>2</sup> or weaker but drastically decreased after 26.4 W/cm<sup>2</sup> or higher. These findings showed, for the first time, that the safety margin of long-term, at least several hours, cochlear laser stimulation exists and will contribute to the appropriate delimitation of the safe and effective laser stimulation parameters in future research.
Bibliometric analysis of microphthalmos and anophthalmos over 20 years: from 2004 to 2023
2024-10-23

AIM: To conduct a bibliometric analysis of studies on microphthalmos and anophthalmos (M/A), explore research hotspots, and provide information on future research interests in this field to benefit clinicians and researchers. METHODS: Totally 751 publications related to M/A from the year 2004 to 2023 were collected from the Web of Science Core Collection database. These publications consist of both original and review articles, that are composed in English. The contributions of different countries, institutions, journals, and authors were analyzed, and network analysis was conducted by using Microsoft Excel 2021, VOSviewer, and R Studio to visualize research hotspots. RESULTS: Among all publications included, the highest number of publications came from USA (218, 29.03%). China followed with 99 publications (13.18%), and England with 86 publications (11.45%). The publications from the USA had the highest frequency of citations, with 16 699 citations, and the highest H-index of 49. The American Journal of Medical Genetics Part A (43, 5.73%) published the largest number of papers, and the University of London had the most publications (41, 5.46%). The genetic and molecular mechanisms of M/A were still unclear and the clinical intervention for M/A had gained a lot of attention as an emerging area of interest. CONCLUSION: Data have been gathered on the yearly count of published materials and citations, as well as the rise in publication trends, the efficiency of regions or countries, authors, journals, and organizations, along with the high-cited publications in M/A. The recent trend of research has shifted from genetic mechanisms to different clinical phenotypes and corresponding clinical interventions, which can give direction to future research.
A new class of receptors: Lipids regulate mammalian Gsα-stimulated adenylyl cyclase activities via their membrane anchors
2024-10-23

The biosynthesis of cAMP by mammalian membrane-bound adenylyl cyclases (mACs) is predominantly regulated by G-protein-coupled-receptors (GPCRs). Up to now the two hexahelical transmembrane domains of mACs were considered to fix the enzyme to membranes. Here we show that the transmembrane domains serve in addition as signal receptors and transmitters of lipid signals that control Gsα-stimulated mAC activities. We identify aliphatic fatty acids and anandamide as receptor ligands of mAC isoforms 1 to 7 and 9. The ligands enhance (mAC isoforms 2, 3, 7, and 9) or attenuate (isoforms 1, 4, 5, and 6) Gsα-stimulated mAC activities in vitro and in vivo. Substitution of the stimulatory membrane receptor of mAC3 by the inhibitory receptor of mAC5 results in a ligand inhibited mAC5- mAC3 chimera. Thus, we discovered a new class of membrane receptors in which two signaling modalities are at a crossing, direct tonic lipid and indirect phasic GPCR-Gsα signaling regulating the biosynthesis of cAMP.
Enhancing Semiconductor Nanoprobing Procedures with AI-Driven Tip Detection
2024-10-23

Abstract The automation of nanoprobing application relies on the accurate detection of probe tips in scanning electron microscope (SEM) images. This work explores the application of deep learning models to automate and improve this critical process. Different models such as Mask R-CNN, YOLOv8 and RTMDet, trained on a specialized dataset, are used to accurately detect, segment and localize probe tips in SEM images, even under challenging conditions. Results show that these models have the potential to improve the automation of nanoprobing workflows, particularly in automatic tip positioning and crash prevention. Future work will focus on production-level deployment and the integration of tracking algorithms.
Change in Femoral Offset after Closed Reduction and Dynamic Hip Screw Osteosynthesis Via Lateral Approach in Patients with Medial Femoral Neck Fracture: A Retrospective Analysis
2024-10-23

Objective Closed reduction and dynamic hip screw (DHS) osteosynthesis are preferred as joint‐preserving therapy in case of medial femoral neck fractures (MFNFs). A change in the femoral offset (CFO) can cause gait abnormality, impingement, or greater trochanteric pain syndrome. It is unknown whether the femoral offset (FO) can be postoperatively fully restored. The aim of the study was to investigate the extent of a possible CFO in hip joints after DHS osteosynthesis in the case of an MFNF. Methods In this retrospective study, 104 patients (mean age: 71.02 years, men: n = 50, women: n = 54) with MFNF who underwent closed reduction and DHS osteosynthesis were analyzed by postoperative x‐rays to assess CFO between the operated (OS) and nonoperated joint side (NOS). The studies covered the time period 2010–2020. A statistical comparison was performed between the mean values of FO between OS and NOS, taking into account patient age, gender, and fracture severity. Results All operated hip joints showed a CFO. In 76.0% (79 of 104), the FO decreased (FOD), and in 24.0% (25 of 104), the FO increased (FOI). A critical CFO (&gt;15% CFO) was detected in 52.9% (55 of 104). In hip joints with postoperative FOD, the mean FO between NOS (49.15 mm [±6.56]) and OS (39.32 mm [±7.87]) and in hip joints with postoperative FOI the mean FO between NOS (41.59 [±8.21]) and OS (47.27 [±6.68]) differed significantly ( p &lt; 0.001). Preoperative FO ( r S : −0.41; p &gt; 0.001) and caput–collum–diaphyseal angle (CCD; r S : 0.34; p &gt; 0.001) correlated with postoperative CFO. FOD was found in hip joints with a preoperative FO &gt;44 mm and CCD &lt;134° vice versa FOI in hip joints with a preoperative FO &lt;44 mm and CCD &gt;134°. Conclusion Closed reduction and DHS osteosynthesis in patients with MFNF result in a clustered significant CFO. The individual FO should be taken into account pre‐ and intraoperatively to avoid a postoperative extensive CFO.
Prevalence of Dunning-Kruger effect in first semester medical students: a correlational study of self-assessment and actual academic performance
2024-10-24

Abstract Introduction The ability to self-assess is a crucial skill in identifying one’s own strengths and weaknesses and in coordinating self-directed learning. The Dunning-Kruger effect occurs when limited knowledge causes individuals to overestimate their competence and underestimate others’, leading to poor self-assessment and unrecognized incompetence. To serve as a foundation for developing strategies to improve self-assessment, the self-assessment abilities of first-semester students were assessed. Methods In the final weeks of the summer 2021, winter 2021/22, and summer 2022 semesters, the academic performance (oral anatomy exam) of first semester students was assessed (0–15 points). Before the exam results were announced, students were asked to self-assess their performance. Results Exam scores ( M = 10.64, SD = 2.95) and self-assessed scores ( M = 10.38, SD = 2.54) were comparable. The absolute difference between them, as a measure of self-assessment ability ranged from − 9 to + 9 points ( M = -0.26, SD = 2.59). Among participants ( N = 426), 18.5% assessed themselves accurately, 35.5% overestimated, and 46.0% underestimated their performance. The correlation between actual score and self-assessment was ρ = -0.590 ( p &lt; 0.001), reflecting the Dunning-Kruger effect. When separated by gender, correlation for females was ρ = -0.591 ( p &lt; 0.001), and for males ρ = -0.580 ( p &lt; 0.001). Conclusions Realistic self-assessment is a challenge for first-semester students. The data indicate that females tend to overestimate their performance while males underestimate theirs. A pronounced Dunning-Kruger effect is evident in both genders, with significant negative correlations between self-assessment and actual performance. There are several reasons for the occurrence of the Dunning-Kruger effect. Considering that the COVID-19 pandemic influenced learning environments, collaborative learning was significantly restricted. The lack of opportunities for comparison could potentially lead to unrealistic self-assessment.
Host blood protein biomarkers to screen for tuberculosis disease: a systematic review and meta-analysis
2024-10-24

ABSTRACT Non-sputum tests are needed to improve tuberculosis (TB) diagnosis and close the diagnostic gap. The World Health Organization’s target product profile (TPP) for point-of-care (POC) screening tests requires a minimum sensitivity of 90% and a specificity of 70%. Our objective was to identify host blood protein biomarkers meeting TPP criteria. A systematic review was conducted and reported following PRISMA guidelines. Data extraction and quality assessment with Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) were completed for the included studies. Heterogeneity was assessed. For biomarkers reporting sensitivity and specificity in at least four studies, a random-effects meta-analysis was performed for biomarkers with similar cut-offs. We screened 4,651 citations and included 65 studies that enrolled 16,010 participants and evaluated 156 host proteins. Most (47/65) studies enrolled adult pulmonary TB (PTB), with 15 studies in adult extra-pulmonary TB and 5 in children. Small early-stage discovery studies with case-control design were common (24/65) and had a high risk of bias. For adult PTB, CRP, IP-10, NCAM-1, and SAA met TPP criteria in high-quality studies. There was a high degree of heterogeneity in biomarker cut-offs and study design. CRP at 10 mg/L cut-off was meta-analyzed from 10 studies; pooled sensitivity 86% [95% confidence interval (CI): 80–95] and pooled specificity 67% (95% CI: 54–79). In people living with HIV (six studies), CRP pooled sensitivity was 93% (95% CI: 90–95), and pooled specificity was 59% (95% CI: 40–78). We identified promising biomarkers that performed well in high-quality studies. Data overall are limited and highly heterogenous. Further standardized validation across subgroups in prospective studies is needed before translating into POC assays. IMPORTANCE To our knowledge, this is the first comprehensive systematic review of host blood protein biomarkers for tuberculosis (TB), and we identified promising biomarkers for a TB screening test.