julilili42/papers huggingface dataset:
Candidate Key Proteins in Tinnitus—A Bioinformatic Study of Synaptic Transmission in the Cochlear Nucleus
2024-07-19

The aim of this study was to identify key proteins of synaptic transmission in the cochlear nucleus (CN) that are involved in normal hearing, acoustic stimulation, and tinnitus. A gene list was compiled from the GeneCards database using the keywords “synaptic transmission” AND “tinnitus” AND “cochlear nucleus” (Tin). For comparison, two gene lists with the keywords “auditory perception” (AP) AND “acoustic stimulation” (AcouStim) were built. The STRING protein–protein interaction (PPI) network and the Cytoscape data analyzer were used to identify the top two high-degree proteins (HDPs) and their high-score interaction proteins (HSIPs), together referred to as key proteins. The top1 key proteins of the Tin-process were BDNF, NTRK1, NTRK3, and NTF3; the top2 key proteins are FOS, JUN, CREB1, EGR1, MAPK1, and MAPK3. Highly significant GO terms in CN in tinnitus were “RNA polymerase II transcription factor complex”, “late endosome”, cellular response to cadmium ion”, “cellular response to reactive oxygen species”, and “nerve growth factor signaling pathway”, indicating changes in vesicle and cell homeostasis. In contrast to the spiral ganglion, where important changes in tinnitus are characterized by processes at the level of cells, important biological changes in the CN take place at the level of synapses and transcription.
Characterization of Monoclonal Antibody Charge Variants under Near-Native Separation Conditions using Nanoflow Sheath Liquid Capillary Electrophoresis-Mass Spectrometry
2024-07-19

Monoclonal antibodies (mAbs) undergo multiple post-translational modifications (PTMs), e.g., charge variants, oxidation, etc., during production and storage, necessitating evaluation of the resulting PTMs as critical quality attributes (CQA) for protein quality and safety. Charge variants PTMs can be separated using capillary zone electrophoresis (CZE). The CZE EACA method developed by He et al. (2011) with UV detection is applied routinely in the pharmaceutical industry for analyzing charge variants. However, the method cannot be directly hyphenated with mass spectrometry (MS), preventing direct identification of separated charge variants due to the non-volatile background electrolyte (BGE), which hinders reliable charge variant identification. This study presents a CZE-UV/MS method using a neutral static capillary coating of hydroxypropyl methylcellulose combined with a volatile BGE at pH 5.0 to allow MS-compatible mAb charge variant separations. The effect of several parameters, including pH and concentration of BGE, voltage, and injected mAb concentrations in terms of separation performance on a panel of mAbs was investigated. The final method was tested with mAbs of IgG subclasses (IgG1 and IgG4) with different pI (7.4-9.2), and degrees of heterogeneity. Basic and acidic variants were separated from the parent mAb using a BGE of 50 mM acetic acid adjusted at pH 5.0. A linear correlation in relative charge variant abundance was obtained between our method and the EACA method. CZE-MS coupling was accomplished using the nanoCEasy, a low-flow sheath liquid interface, which enabled the identification and quantitation of basic, acidic, and incomplete pyroglutamate variants, and glycoforms of the tested mAbs.This method can be a useful tool for in-depth charge variants characterization of mAbs.
Feasibility and acceptance of KIDSCREEN-52 as a screening tool for unmet needs in children with rare inflammatory diseases
2024-07-19

<title>Abstract</title> <bold>Background:</bold> Children living with rare diseases often face significant psychosocial challenges; recognizing and addressing these effectively is crucial. However, there is a paucity of comprehensive screening tools. This study aimed to assess the feasibility and acceptance of the comprehensive KIDSCREEN-52 tool in identifying unmet needs of children with rare inflammatory diseases and their caregivers and identifying factors associated with low health-related quality of life (HRQoL). <bold>Methods</bold> A prospective single-center study of consecutive pediatric patients aged 8-18 with inflammatory diseases and their caregivers was performed to assess HRQoL utilizing the multidimensional KIDSCREEN-52 self-report and proxy tool. The validated KIDSCREEN-52 tool is available in 13 languages with corresponding Norm Data. It captures HRQoL across 10 domains including 52 inquiries. HRQoL of children with rare inflammatory diseases was described utilizing the multidimensional KIDSCREEN-52 self-report and proxy tool. The feasibility and acceptability of KIDSCREEN-52 was determined using a simple, dichotomous three item acceptance tool. Factors associated with low self-reported HRQoL were explored. <bold>Results:</bold> A total of 104 participants, comprising 51 pediatric patients and their 53 caregivers, were included. The patients were 35 females and 16 males, with a median age of 16 years (range: 9-18). Among them, 25 (49%) had autoinflammatory diseases, 26 (51%) had rheumatic diseases. Mean values from self-reports and proxies were consistent with the Norm Data across all domains. Self-report and proxy assessments showed high-degree agreement. Patients reported lower HRQoL levels compared to the control population in nearly all domains. Both caregivers and children expressed strong acceptance of the KIDSCREEN-52 questionnaire's clarity, relevance, and adequacy. The overall completion rate was 75%, the mean completion time 17 minutes (range: 10-25). Factors associated with low HRQoL included female gender, adolescent age and evidence of a rheumatic disease. <bold>Conclusion:</bold> The KIDSCREEN-52 demonstrated promise as a feasible and accepted tool for capturing the HRQoL and identifying unmet needs in children with rare inflammatory diseases. Its comprehensiveness and the availability in multiple languages with corresponding Norm Data, offers a unique opportunity to implement strategies to identify and address HRQoL challenges of children with rare diseases in routine clinical care.
Role of intraoperative ultrasound and MRI to aid grade of resection of pediatric low-grade gliomas. Accumulated experience from 4 centers
2024-07-19

<title>Abstract</title> Purpose Pediatric low-grade gliomas (pLGG) are the most common brain tumors in children and achieving complete resection (CR) is the most important prognostic factor. There are multiple intraoperative tools to optimise the extent of resection (EOR). This article investigates and discusses the role of intraoperative ultrasound (iUS) and intraoperative magnetic resonance imaging (iMRI) in the treatment of pLGG. Methods The tumor registries at Tuebingen, Rome and Pretoria were searched for pLGG with the use of iUS and data on EOR. The tumor registries at Liverpool and Tuebingen were searched for pLGG with the use of iMRI where preoperative CR was the surgical intent. Different iUS and iMRI machines were used in the 4 centers. Results We included 111 operations which used iUS and 182 operations using iMRI. Both modalities facilitated intended CR in hemispheric supra- and infratentorial location in almost all cases. In more deep seated tumor location like supratentorial midline tumors, iMRI has advantages over iUS to visualize residual tumor. Functional limitations limiting CR arising from eloquent involved or neighboring brain tissue apply to both modalities in the same way. In the long-term follow-up, both iUS and iMRI show that achieving a complete resection on intraoperative imaging significantly lowers recurrence of disease (Chi-square test, p &lt; 0.01). Conclusion iUS and iMRI have specific pros and cons, but both have been proven to improve achieving CR in pLGG. Due to advances in image quality, cost- and time-efficiency, and efforts to improve the user interface, iUS has emerged as the most accessible surgical adjunct to date to aid and guide tumor resection. Since the EOR has the most important effect on long term outcome and disease control of pLGG in most locations, we strongly recommend taking all possible efforts to use iUS in any surgery, independent of intended resection extent, and iMRI if locally available.
Evaluating the Effectiveness of the Nudge Theory in Improving the Oral Self-Care of Schoolchildren with Refugee and Immigrant Backgrounds in Mashhad, Iran
2024-07-19

Nudge theory proposes using subtle interventions to encourage individuals to make better decisions. The aim of this study was to evaluate the effectiveness of the Nudge theory in plaque control and assess caries experience among third-grade primary schoolchildren with refugee and immigrant backgrounds in Mashhad, Iran. Moreover, Afghan and Iranian schoolchildren were compared to assess differences in oral health outcomes. A quasi-experimental field trial was conducted in three public primary schools, comprising 309 participants approximately 9 years old. Interventions were randomly assigned to three schools: School I Messages based on Social Norms (MSN), School II Messages based on Fear of Negative Outcome (MFNO), and School III control group (C). MSN and MFNO received customized motivational video clips at baseline, while C only received Oral hygiene instruction (OHI). All participants received OHI, a brush, and toothpaste. Baseline plaque index (PI) and caries experience in primary and permanent dentition (dmft/DMFT) were recorded. PI was reassessed at two weeks, two months, and six months post-intervention. All data were subjected to statistical analysis. The mean PI decreased significantly in all three groups at the two-week follow-up (p &lt; 0.01). The PI improvements declined over a six-month follow-up period in all groups, and the mean PI difference after six months compared to the pre-intervention was significant only in MSN and MFNO (p &lt; 0.01), while C reverted almost to the pre-study level. Schoolchildren with at least one filled tooth or Iranian nationality showed a greater PI reduction (p &lt; 0.01, p = 0.05). The overall mean ± SD dmft and DMFT were 4.24 ± 2.11 and 1.70 ± 1.24, respectively. Among all the examined participants, 32 (10.40%) individuals were caries-free. The mean dmft was statistically significantly higher in Afghan children than in Iranians (p = 0.01). MSN was more effective on PI reduction in the short term, while MFNO was more long-lasting. Using the Nudge theory via visual aids was more effective in motivating children to perform better oral self-care than solely traditional OHI.
Rapid Detection of Cleanliness on Direct Bonded Copper Substrate by Using UV Hyperspectral Imaging
2024-07-19

In the manufacturing process of electrical devices, ensuring the cleanliness of technical surfaces, such as direct bonded copper substrates, is crucial. An in-line monitoring system for quality checking must provide sufficiently resolved lateral data in a short time. UV hyperspectral imaging is a promising in-line method for rapid, contactless, and large-scale detection of contamination; thus, UV hyperspectral imaging (225–400 nm) was utilized to characterize the cleanliness of direct bonded copper in a non-destructive way. In total, 11 levels of cleanliness were prepared, and a total of 44 samples were measured to develop multivariate models for characterizing and predicting the cleanliness levels. The setup included a pushbroom imager, a deuterium lamp, and a conveyor belt for laterally resolved measurements of copper surfaces. A principal component analysis (PCA) model effectively differentiated among the sample types based on the first two principal components with approximately 100.0% explained variance. A partial least squares regression (PLS-R) model to determine the optimal sonication time showed reliable performance, with R2cv = 0.928 and RMSECV = 0.849. This model was able to predict the cleanliness of each pixel in a testing sample set, exemplifying a step in the manufacturing process of direct bonded copper substrates. Combined with multivariate data modeling, the in-line UV prototype system demonstrates a significant potential for further advancement towards its application in real-world, large-scale processes.
Tidal influence on flow dynamics of Dotson Ice Shelf, West Antarctica
2024-07-19

Abstract. On Dotson Ice Shelf, Antarctica, ice velocities derived from satellite image pairs and in-situ GPS measurements reveal an oscillating flow pattern that is correlated with tide height. The tidally-affected flow pattern is of limited extent, in an area near the Wunneberger Rock nunatak in the outflow of Kohler Glacier. Comparing variations in the region’s flow velocity derived from a series of 16-day repeat-pass Landsat 8 image pairs spanning 2014–2020, and a 64-hour GPS record in 2022 with the CATS2008 and TPXO9 tide-height models, indicates a significant correlation between tidal uplift and the direction of ice-flow. During high-tide periods the ice-shelf flows in a true north direction, while at low-tide periods flow direction shifts towards the northeast, marking an approximately 40 ̊ change in flow direction. GPS measurements describe a continuous corkscrew-like motion of the ice-shelf surface, confirming the link between tide height and ice-flow direction. We attribute the observed pattern to tidally controlled changes of buttressing along the ice-shelf margins and the fin-like shape of Wunneberger Rock. This leads to a dual pattern: (i) fast flow across the grounding line of the tributary Kohler Glacier during high tides aligning with Wunneberger Rock’s summit ridge; and (ii) slow flow during low tide height facing its flanks. We suggest that the link between tides and ice dynamics is related to the rapid ice-shelf thinning in the area. In light of the continued thinning of ice shelves surrounding Antarctica, we anticipate similar variations in flow direction and speed arising from changes in tidal influence on buttressing from pinning points and grounding zones.
Response and outcome of patients with melanoma skin metastases and immune checkpoint inhibition
2024-07-20

Abstract It is known, that different metastatic organ systems respond differently to immune checkpoint inhibitors (ICIs). In this study, we aimed to investigate the extent to which skin/subcutaneous metastases respond to ICI or targeted therapies (TTs) and whether the response rate differs from that of distant metastases in the same patient. Patients with melanoma diagnosed between January 2021 and September 2023 with at least one skin/subcutaneous metastasis who had received therapy with ICI or TT in an advanced setting were included in the analysis. Best overall response (BOR) was classified according to the revised response evaluation criteria in solid tumors (RECIST). The BOR of skin metastases and visceral metastases to ICI and TT was compared using the chi‐square test. Skin metastases treated with ICI a first‐line setting showed an overall response rate (ORR) of 44.1%. In contrast, visceral metastases had a higher ORR of 51.1%. However, the difference was not statistically significant ( p = .77). Regarding TT, the ORR for skin metastases was 57.1%, compared to 38.5% for visceral metastases ( p = .59). Interestingly, the ORR for skin/subcutaneous metastases was notably lower with ICI compared to visceral metastases, in contrast to patients who underwent TT. Skin metastases showed a poorer response to ICI than visceral metastases. Therefore, careful monitoring is recommended to detect non‐response early in patients with skin metastases as skin metastases may have a worse response than TT. A larger cohort is needed for a comprehensive analysis and confirmation of our results.
The impact of the COVID-19 pandemic on administrative eating disorder prevalence in the outpatient sector and on severity of anorexia nervosa
2024-07-20

Abstract The COVID-19 pandemic appears to have had a considerable impact on the mental health of children and adolescents, particularly regarding eating disorders. However, it remains unclear whether the pandemic affected only the frequency or also the severity of eating disorders. We examined potential pandemic-related changes in the administrative prevalence of eating disorders in the outpatient sector compared with other mental disorders using German statutory health insurance data for the age group 10 to 16 years. We also examined disorder severity of anorexia nervosa using data from the multicenter German Registry of Children and Adolescents with Anorexia Nervosa in the same age group. Our results showed a marked increase in the administrative prevalence of eating disorders (based on documented diagnoses) in the outpatient sector among girls but not among boys. A similar pattern was found for internalizing disorders, whereas the administrative prevalences of externalizing disorders decreased. Regarding the severity of anorexia nervosa among inpatients, we found no pandemic-related changes in body mass index standard deviation score at admission, body weight loss before admission, psychiatric comorbidities and psychopharmacological medication. Given the administrative prevalence increase in the outpatient sector, the lack of impact of the pandemic on the inpatient sector may also be partly due to a shift in healthcare utilization towards outpatient services during the pandemic. Thus, the higher number of children and adolescents requiring specialized and timely outpatient care may be a major concern under pandemic conditions.
Targeted ultra-high performance liquid chromatography-tandem mass spectrometry assay for the quantification of medium-chain phosphatidylcholines in platelets of coronary artery disease patients
2024-07-20

In a recent untargeted clinical lipidomics study of platelets of coronary artery disease (CAD) patients, medium-chain phosphatidylcholines (MCPCs) with C8 and C10 fatty acyl residues were found significantly upregulated in the patient group with acute coronary syndrome (ACS) as compared to chronic coronary syndrome (CCS) and healthy controls. To support this finding, this work presents the development and optimization of a targeted UHPLC-QTrap-MS/MS method with multiple reaction monitoring acquisition for the quantitative analysis of MCPCs (PC 10:0/8:0, PC 16:0/8:0, PC 10:0/20:4 and PC 10:0/10:0) in platelets for biomarker validation. A systematic optimization of chromatographic and mass spectrometric parameters was performed. A charged surface hybrid CSH C18 (1.7 μm, 130 Å) column and fine-tuned gradient elution with 2-propanol/acetonitrile and ammonium acetate as additive to the mobile phase was employed in the final method in ESI negative mode. Four selected PC standards (PC 6:0/6:0, PC 8:0/8:0, PC 10:0/10:0 and PC 12:0/12:0), which cover well the carbon and retention rime range of the target analytes, were used for the optimization process and calibration. Quantification was based on matrix-matched calibration with these four selected commercially available MCPC standards as surrogate calibrants and PC 6:0/6:0(d22) as internal standard. Furthermore, an organic solvent and fatty acyl carbon number-corrected response factor approach gave also accuracies within acceptance limits of bioanalytical validation guidelines and has more generic applicability. Compared to the previous untargeted RPLC-ESI-QTOF-MS/MS method, the optimized targeted UHPLC-QTrap-MS/MS assay showed increased sensitivity and selectivity for the detection of medium-chain PCs in platelet samples of CAD (LOQs in the range of 0.5–5 nmol/L). The method performance parameters indicated its suitability for a future biomarker validation study of MCPCs in platelets.
A De Lellis–Müller type estimate on the Minkowski lightcone
2024-07-20

Abstract We prove an analogue statement to an estimate by De Lellis–Müller in <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msup> <mml:mrow> <mml:mi>R</mml:mi> </mml:mrow> <mml:mn>3</mml:mn> </mml:msup> </mml:math> on the standard Minkowski lightcone. More precisely, we show that under some additional assumptions, any spacelike cross section of the standard lightcone is <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msup> <mml:mi>W</mml:mi> <mml:mrow> <mml:mn>2</mml:mn> <mml:mo>,</mml:mo> <mml:mn>2</mml:mn> </mml:mrow> </mml:msup> </mml:math> -close to a round surface provided the trace-free part of a scalar second fundamental form A is sufficiently small in <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msup> <mml:mi>L</mml:mi> <mml:mn>2</mml:mn> </mml:msup> </mml:math> . To determine the correct intrinsically round cross section of reference, we define an associated 4-vector, which transforms equivariantly under Lorentz transformations in the restricted Lorentz group. A key step in the proof consists of a geometric, scaling invariant estimate, and we give two different proofs. One utilizes a recent characterization of singularity models of null mean curvature flow along the standard lightcone by the author, while the other is heavily inspired by an almost-Schur lemma by De Lellis–Topping.
Secretive interaction
2024-07-20

We study the behaviour of n players engaged in a conversation, each attempting to predict the behaviour of the others. We prove that, under a certain notion of interaction, it is possible to learn all other players, but, generally, not without being learned back. We then focus on the interaction of two players and consider, for different methodological restrictions based on the philosophy of science, whether some form of secretive learning can be achieved.
Prognostic impact of selection criteria of current adjuvant endocrine therapy trials NATALEE and monarchE in postmenopausal HRpos/HER2neg breast cancer patients treated with upfront letrozole
2024-07-21

Patient populations eligible for monarchE and NATALEE trials differed. Nearly a third of the postmenopausal HRpos population, previously under upfront letrozole treatment, met the NATALEE prognostic eligibility criteria. As certain eligible groups had a prognosis similar to non-eligible patients, it might be interesting to explore additional patient groups for CDK4/6i therapy.
Next-generation phenotyping integrated in a national framework for patients with ultrarare disorders improves genetic diagnostics and yields new molecular findings
2024-07-22

Abstract Individuals with ultrarare disorders pose a structural challenge for healthcare systems since expert clinical knowledge is required to establish diagnoses. In TRANSLATE NAMSE, a 3-year prospective study, we evaluated a novel diagnostic concept based on multidisciplinary expertise in Germany. Here we present the systematic investigation of the phenotypic and molecular genetic data of 1,577 patients who had undergone exome sequencing and were partially analyzed with next-generation phenotyping approaches. Molecular genetic diagnoses were established in 32% of the patients totaling 370 distinct molecular genetic causes, most with prevalence below 1:50,000. During the diagnostic process, 34 novel and 23 candidate genotype–phenotype associations were identified, mainly in individuals with neurodevelopmental disorders. Sequencing data of the subcohort that consented to computer-assisted analysis of their facial images with GestaltMatcher could be prioritized more efficiently compared with approaches based solely on clinical features and molecular scores. Our study demonstrates the synergy of using next-generation sequencing and phenotyping for diagnosing ultrarare diseases in routine healthcare and discovering novel etiologies by multidisciplinary teams.