julilili42/papers huggingface dataset:
Childhood trauma and differential response to long-term psychoanalytic versus cognitive–behavioural therapy for chronic depression in adults
2024-08-09

Background Childhood trauma is a major risk factor for chronic depression. It has been suggested that adults with chronic depression who have experienced childhood trauma may require long-term treatment owing to a breakdown of basic trust and related difficulties in developing a productive therapeutic relationship. Aims As empirical studies have been preliminary and scarce, we studied the effects of psychoanalytic therapy (PAT) versus cognitive–behavioural therapy (CBT) for chronic depression in adults with a history of childhood trauma. In this subgroup, we expected a greater symptom reduction in PAT compared with CBT. Method In a large trial of long-term psychotherapies for chronic depression (LAC-Study; Clinical Trial Register ISRCTN91956346), 210 adults received open-ended CBT or PAT in an out-patient setting and were examined yearly over 5 years on the Beck Depression Inventory – II (BDI-II). Based on a linear mixed model approach, we tested participant-reported childhood trauma based on the Childhood Trauma Questionnaire (CTQ) as a predictor and moderator of treatment outcome. CTQ subscales were examined exploratively. Results Depressive symptoms decreased over time ( b = −4.55, s.e. = 0.90, 95% CI −6.32 to −2.81, T = −5.08; P &lt; 0.001). A significant three-way interaction between childhood trauma, time and therapy group ( b = −0.05, s.e. = 0.02, 95% CI −0.09 to −0.01, T = −2.42; P = 0.016) indicated that participants with childhood trauma profited especially well from PATs. Conclusions Our results indicate differential benefits from PAT compared with CBT among adults with chronic depression and a history of childhood trauma. The results have important implications for differential indication and policy.
Vitamin C-Dependent Uptake of Non-Heme Iron by Enterocytes, Its Impact on Erythropoiesis and Redox Capacity of Human Erythrocytes
2024-08-09

In the small intestine, nutrients from ingested food are absorbed and broken down by enterocytes, which constitute over 95% of the intestinal epithelium. Enterocytes demonstrate diet- and segment-dependent metabolic flexibility, enabling them to take up large amounts of glutamine and glucose to meet their energy needs and transfer these nutrients into the bloodstream. During glycolysis, ATP, lactate, and H+ ions are produced within the enterocytes. Based on extensive but incomplete glutamine oxidation large amounts of alanine or lactate are produced. Lactate, in turn, promotes hypoxia-inducible factor-1α (Hif-1α) activation and Hif-1α-dependent transcription of various proton channels and exchangers, which extrude cytoplasmic H+-ions into the intestinal lumen. In parallel, the vitamin C-dependent and duodenal cytochrome b-mediated conversion of ferric iron into ferrous iron progresses. Finally, the generated electrochemical gradient is utilized by the divalent metal transporter 1 for H+-coupled uptake of non-heme Fe2+-ions. Iron efflux from enterocytes, subsequent binding to the plasma protein transferrin, and systemic distribution supply a wide range of cells with iron, including erythroid precursors essential for erythropoiesis. In this review, we discuss the impact of vitamin C on the redox capacity of human erythrocytes and connect enterocyte function with iron metabolism, highlighting its effects on erythropoiesis.
Implementation of PET/CT in radiation oncology—a patterns-of-care analysis of the German Society of Nuclear Medicine and the German Society of Radiation Oncology
2024-08-09

Abstract Background The use of positron-emission tomography (PET)/computed tomography (CT) in radiation therapy (RT) has increased. Radiation oncologists (RadOncs) have access to PET/CT with a variety of tracers for different tumor entities and use it for target volume definition. The German Society of Nuclear Medicine (DGN) and the German Society of Radiation Oncology (DEGRO) aimed to identify current patterns of care in order to improve interdisciplinary collaboration. Methods We created an online survey on participating RadOncs’ use of PET tracers for different tumor entities and how they affect RT indication, dose prescription, and target volume definition. Further topics were reimbursement of PET/CT and organizational information (fixed timeslots and use of PET with an immobilization device [planning/RT-PET]). The survey contained 31 questions in German language (yes/no questions, multiple choice [MC] questions, multiple select [MS] questions, and free-text entry options). The survey was distributed twice via the DEGRO member mailing list. Results During the survey period (May 22–August 7, 2023) a total of 156 RadOncs (13% of respondents) answered the survey. Among these, 59% reported access to diagnostic PET/CT within their organization/clinic and 24% have fixed timeslots for their patients. 37% of survey participants can perform RT-PET and 29% have the option of providing a dedicated RT technician for planning PET. Besides [ 18 F]-fluorodeoxyglucose (FDG; mainly used in lung cancer: 95%), diagnostic prostate-specific membrane antigen (PSMA)-PET/CT for RT of prostate cancer is routinely used by 44% of participants (by 64% in salvage RT). Use of amino acid PET in brain tumors and somatostatin receptor PET in meningioma is low (19 and 25%, respectively). Scans are reimbursed through private (75%) or compulsory (55%) health insurance or as part of indications approved by the German Joint Federal Committee ( Gemeinsamer Bundesausschuss ; 59%). 98% of RadOncs agree that PET impacts target volume definition and 62% think that it impacts RT dose prescription. Discussion This is the first nationwide survey on the role of PET/CT for RT planning among RadOncs in Germany. We find high acceptance of PET results for treatment decisions and target volume definition. Planning PET comes with logistic challenges for different healthcare settings (e.g., private practices vs. university hospitals). The decision to request PET/CT is often based on the possibility of reimbursement. Conclusion PET/CT has become an important tool for RadOncs, with several indications. However, access is still limited at several sites, especially for dedicated RT-PET. This study aims to improve interdisciplinary cooperation and adequate implementation of current guidelines for the treatment of various tumor entities.
Phenanthrenes from Juncus articulatus with Antibacterial and Biofilm Formation Inhibitory Activity
2024-08-09

Continuing our search for bioactive compounds in species from the Juncaceae family, <i>Juncus articulatus</i> was investigated. Ten previously undescribed phenanthrenes─articulins A-J (<b>1</b>-<b>10</b>)─and ten known compounds─juncuenin B, dehydrojuncuenin B, juncatrin B, ensifolins E, F, H, I, K, juncuenin D, and luzulin A (<b>11</b>-<b>20</b>)─along with other compounds, have been isolated and identified. The isolated compounds were evaluated for antibacterial activity against <i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i>, methicillin-susceptible <i>Staphylococcus aureus</i> (MSSA), and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). Compounds <b>12</b> and <b>14</b> exhibited the most potent activity against planktonic and sessile MSSA and MRSA with minimum inhibitory concentration (MIC) values of 15.1 μM (<b>12</b> for both bacterial strains) and 15.3 μM (<b>14</b> for both bacterial strains). Compounds <b>15</b>, <b>17</b>, and <b>18</b> also exhibited activity against both strains, although to a lower extent, with MIC values ranging from 30.0 to 56.8 μM. The inhibition of biofilm formation of these compounds was observed at 15.1-114.3 μM. This study elucidates the phenanthrene composition of <i>J. articulatus</i> and the antibacterial effect of these compounds.
Long Non-Coding RNA Profile in Genetic Symptomatic and Presymptomatic Frontotemporal Dementia: A GENFI Study
2024-08-09

Background: Long non-coding RNAs (lncRNAs) play crucial roles in gene regulation and are implicated in neurodegenerative diseases, including frontotemporal dementia (FTD). However, their expression patterns and potential as biomarkers in genetic FTD involving Chromosome 9 Open Reading Frame (C9ORF72), Microtubule Associated Protein Tau (MAPT), and Progranulin (GRN) genes are not well understood. Objective: This study aimed to profile the expression levels of lncRNAs in peripheral blood mononuclear cells collected within the GENetic Frontotemporal dementia Initiative (GENFI). Methods: Fifty-three lncRNAs were analyzed with the OpenArray Custom panel, in 131 patients with mutations in C9ORF72, MAPT, and GRN, including 68 symptomatic mutation carriers (SMC) and 63 presymptomatic mutation carriers (PMC), compared with 40 non-carrier controls (NC). Results: Thirty-eight lncRNAs were detectable; the relative expression of NEAT1 and NORAD was significantly higher in C9ORF72 SMC as compared with NC. GAS5 expression was instead significantly lower in the GRN group versus NC. MAPT carriers showed no significant deregulations. No significant differences were observed in PMC. Disease duration did not correlate with lncRNA expression. Conclusions: NEAT1 and NORAD are upregulated in C9ORF72 SMC and GAS5 levels are downregulated in GRN SMC, underlining lncRNAs’ relevance in FTD and their potential for biomarker development. Further validation and mechanistic studies are crucial for clinical implications.
Shrinking Small Sample Problems in Multilevel Structural Equation Modeling via Regularization of the Sample Covariance Matrix
2024-08-09

Small sample sizes pose a severe threat to convergence and accuracy of between-group level parameter estimates in multilevel structural equation modeling (SEM). However, in certain situations, such as pilot studies or when populations are inherently small, increasing samples sizes is not feasible. As a remedy, we propose a two-stage regularized estimation approach designed for scenarios with both a small number of groups and small group sizes, and a low ICC. The method employs the wide format approach to multilevel SEM, where, at first, the sample covariance matrix is replaced by a shrinkage estimate, and then, this estimate is used to fit the SEM. By means of a simulation study, we evaluated the effectiveness of our two-stage approach. Our findings demonstrate that this method consistently ensures model convergence, provides more accurate between-level estimates, and even improves accuracy of within-level estimates in cases of very small group sizes.
15 Years of Longitudinal Genetic, Clinical, Cognitive, Imaging, and Biochemical Measures in DIAN
2024-08-09

Abstract This manuscript describes and summarizes the Dominantly Inherited Alzheimer Network Observational Study (DIAN Obs), highlighting the wealth of longitudinal data, samples, and results from this human cohort study of brain aging and a rare monogenic form of Alzheimer’s disease (AD). DIAN Obs is an international collaborative longitudinal study initiated in 2008 with support from the National Institute on Aging (NIA), designed to obtain comprehensive and uniform data on brain biology and function in individuals at risk for autosomal dominant AD (ADAD). ADAD gene mutations in the amyloid protein precursor ( APP ), presenilin 1 ( PSEN1 ), or presenilin 2 ( PSEN2 ) genes are deterministic causes of ADAD, with virtually full penetrance, and a predictable age at symptomatic onset. Data and specimens collected are derived from full clinical assessments, including neurologic and physical examinations, extensive cognitive batteries, structural and functional neuro-imaging, amyloid and tau pathological measures using positron emission tomography (PET), flurordeoxyglucose (FDG) PET, cerebrospinal fluid and blood collection (plasma, serum, and whole blood), extensive genetic and multi-omic analyses, and brain donation upon death. This comprehensive evaluation of the human nervous system is performed longitudinally in both mutation carriers and family non-carriers, providing one of the deepest and broadest evaluations of the human brain across decades and through AD progression. These extensive data sets and samples are available for researchers to address scientific questions on the human brain, aging, and AD.
DNA Methylation of PXDN Is Associated with Early-Life Adversity in Adult Mental Disorders
2024-08-09

Early-life adversity (ELA) is characterized by exposure to traumatic events during early periods of life, particularly involving emotional, sexual and/or physical adversities during childhood. Mental disorders are strongly influenced by environmental and lifestyle-related risk factors including ELA. However, the molecular link between ELA and the risk of an adult mental disorder is still not fully understood. Evidence is emerging that long-lasting changes in the epigenetic processes regulating gene expression, such as DNA methylation, play an important role in the biological mechanisms linking ELA and mental disorders. Based on a recent study, we analyzed the DNA methylation of a specific CpG site within the gene PXDN—cg10888111—in blood in the context of ELA across a set of psychiatric disorders, namely Borderline Personality Disorder (BPD), Major Depressive Disorder (MDD) and Social Anxiety Disorder (SAD), and its potential contribution to their pathogenesis. We found significant hypermethylation in mentally ill patients with high levels of ELA compared to patients with low levels of ELA, whereas cg10888111 methylation in healthy control individuals was not affected by ELA. Further investigations revealed that this effect was driven by the MDD cohort. Providing a direct comparison of cg10888111 DNA methylation in blood in the context of ELA across three mental disorders, our results indicate the role of PXDN regulation in the response to ELA in the pathogenesis of mental disorders, especially MDD. Further studies will be needed to validate these results and decipher the corresponding biological network that is involved in the transmission of ELA to an adult mental disorder in general.
Salgo de casa? Salgo a casa? Salgo la casa? Analysis of the crosslinguistic influence on preposition use in motion verb constructions by multilingual German learners of Spanish
2024-08-09

The use of prepositions is one of the most difficult grammar topics for Spanish learners. The high frequency prepositions ‘a’ (‘to, at, on’), ‘de’ (‘from, of’) and ‘en’ (‘in, on, into’) are often confused or omitted, especially in motion verb constructions (e.g., Campillos Llanos, 2014). This can be due to their polysemous character and the low salience. In addition, crosslinguistic influence (Jarvis and Pavlenko, 2008) from the first language as well as additional acquired foreign language(s) play a significant role.In order to analyse the complexity of interlanguage phenomena in the construction [motion verb + a/de/en + noun] to improve acquisition in Spanish classes, it is necessary to study authentic learner data. In this paper, I will discuss the results of an explorative pilot study on crosslinguistic influence carried out at a German grammar school in the federal state Baden-Württemberg in order to find out after which verbs of motion these prepositions are omitted or confused, how often this occurs, and which languages might influence it. The results of two groups of pupils at beginner level with the mean age of 14,03 are compared: The first group (n = 21) learns Spanish as the third foreign language, in addition to English and French, while the second group (n = 16) learns Spanish as the second foreign language after English. Both groups learn the named foreign languages in an instructed setting at school.The pilot study reveals that the prepositions ‘a’ and ‘de’ are much more often confused or omitted in the construction types [llegar/volver/venir + a + noun] (‘arrive/come back/come + to/in + noun’) and [salir/ir + de + noun] (‘leave/go + noun’) compared to [ir + a + noun] (‘go to + noun’). A possible explanation is positive and negative intra- and interlingual transfer of equivalent constructions from different languages. These results form a hypothesis basis that a systematic application of Pedagogical Construction Grammar (Boas, 2022; De Knop and Gilquin, 2016) and multilingual didactics (Fäcke and Meiβner, 2019; García et al., 2020) in Spanish classes to teach these polysemous prepositions could probably be helpful to avoid errors.
Development of Peptoid-Based Heteroaryl-Decorated Histone Deacetylase (HDAC) Inhibitors with Dual-Stage Antiplasmodial Activity
2024-08-09

Dynamics of epigenetic modifications such as acetylation and deacetylation of histone proteins have been shown to be crucial for the life cycle development and survival of Plasmodium falciparum, the deadliest malaria parasite. In this study, we present a novel series of peptoid-based histone deacetylase (HDAC) inhibitors incorporating nitrogen-containing bicyclic heteroaryl residues as a new generation of antiplasmodial peptoid-based HDAC inhibitors. We synthesized the HDAC inhibitors by an efficient multicomponent protocol based on the Ugi four-component reaction. The subsequent screening of 16 compounds from our mini-library identified 6i as the most promising candidate, demonstrating potent activity against asexual blood-stage parasites (IC50 Pf3D7 = 30 nM; IC50 PfDd2 = 98 nM), low submicromolar activity against liver-stage parasites (IC50 PbEEF = 0.25 μM), excellent microsomal stability (t1/2 &gt; 60 min), and low cytotoxicity to HEK293 cells (IC50 = 136 μM).
Wenkai Xu’s contribution to the Discussion of ‘Safe testing’ by Grünwald, De Heide and Koolen
2024-08-09

The authors propose the framework of e-value testing by investigating the grow-rate-optimal (GRO) constructions of e-variables, that incorporate a comprehensive range of testing scenarios for simple alternative, as well as their composite counterparts.The authors illustrate the versatility of e-value tests via three interpretations, drawing connections to 1) game-theoretical viewpoint, 2) conservative pvalues, and 3) Bayes Factors; and devise the determination and connections for optional continuation (OC) and optional stopping (OS) with e-variables, going beyond the capacity of p-value based testing.The proposed GRO-based tests (and the corresponding variants) also embed intriguing connections with information processing, that strengthen the proposal on testing with streaming.
It Is Not All about Alkaloids—Overlooked Secondary Constituents in Roots and Rhizomes of Gelsemium sempervirens (L.) J.St.-Hil
2024-08-09

Gelsemium sempervirens (L.) J.St.-Hil. is an evergreen shrub occurring naturally in North and Middle America. So far, more than 120 alkaloids have been identified in this plant in addition to steroids, coumarins and iridoids, and its use in traditional medicine has been traced back to these compound classes. However, a comprehensive phytochemical investigation of the plant with a special focus on further compound classes has not yet been performed. Therefore, the present study aimed at an extensive HPLC-MSn characterization of secondary metabolites and, for the first time, reports the occurrence of various depsides and phenolic glycerides in G. sempervirens roots and rhizomes, consisting of benzoic and cinnamic acid derivatives as well as dicarboxylic acids. Furthermore, mono- and disaccharides were assigned by GC-MS. Applying the Folin–Ciocalteu assay, the phenolic content of extracts obtained with different solvents was estimated to range from 30 to 50% calculated as chlorogenic acid equivalents per g dry weight and was related to the DPPH radical scavenging activity of the respective extracts. Upon lactic acid fermentation of aqueous G. sempervirens extracts, degradation of phenolic esters was observed going along with the formation of low-molecular volatile metabolites.
Making the effect visible – OX40 targeting nanobodies forin vivoimaging of activated T cells
2024-08-09

Abstract Purpose Human OX40 (hOX40/CD134), a member of the TNF receptor superfamily, is mainly expressed on activated T lymphocytes. Triggered by its ligand OX40L (CD252), it provides costimulatory signals that support the differentiation, proliferation and long-term survival of T cells. Besides being a relevant therapeutic target, hOX40 is also an important biomarker for monitoring the presence or infiltration of activated T cells within the tumor microenvironment (TME), the inflammatory microenvironment (IME) in immune-mediated diseases (IMIDs) and the lymphatic organs. Here, we developed novel single domain antibodies (nanobodies, Nbs) targeting hOX40 to monitor the activation status of T cells by in vivo molecular imaging. Methods Nbs against hOX40 (hOX40-Nbs) were selected from an immunized Nb-library by phage display. The identified hOX40-Nbs were characterized in vitro , including determination of their specificity, affinity, stability, epitope recognition and their impact on OX40 signaling and T cell function. A lead candidate was site-specifically conjugated with a fluorophore via sortagging and applied for noninvasive in vivo optical imaging (OI) of hOX40-expressing cells in a xenograft mouse model. Results Our selection campaign revealed four unique Nbs that exhibit strong binding affinities and high stabilities under physiological conditions. Epitope binning and domain mapping indicated the targeting of at least two different epitopes on hOX40. When analyzing their impact on OX40 signaling, an agonistic effect was excluded for all validated Nbs. Incubation of activated T cells with hOX40-Nbs did not affect cell viability or proliferation patterns, whereas differences in cytokine release were observed. In vivo OI with a fluorophore-conjugated lead candidate in experimental mice with hOX40-expressing xenografts demonstrated its specificity and functionality as an imaging probe. Conclusion Considering the need for advanced probes for noninvasive in vivo monitoring of T cell activation dynamics, we propose, that our hOX40-Nbs have a great potential as imaging probes for noninvasive and longitudinal in vivo diagnostics. Quantification of OX40 + T cells in TME or IME will provide crucial insights into the activation state of infiltrating T cells, offering a valuable biomarker for assessing immune responses, predicting treatment efficacy, and guiding personalized immunotherapy strategies in patients with cancer or IMIDs.
Optimizing Image Quality with High-Resolution, Deep-Learning-Based Diffusion-Weighted Imaging in Breast Cancer Patients at 1.5 T
2024-08-10

The objective of this study was to evaluate a high-resolution deep-learning (DL)-based diffusion-weighted imaging (DWI) sequence for breast magnetic resonance imaging (MRI) in comparison to a standard DWI sequence (DWIStd) at 1.5 T. It is a prospective study of 38 breast cancer patients, who were scanned with DWIStd and DWIDL. Both DWI sequences were scored for image quality, sharpness, artifacts, contrast, noise, and diagnostic confidence with a Likert-scale from 1 (non-diagnostic) to 5 (excellent). The lesion diameter was evaluated on b 800 DWI, apparent diffusion coefficient (ADC), and the second subtraction (SUB) of the contrast-enhanced T1 VIBE. SNR was also calculated. Statistics included correlation analyses and paired t-tests. High-resolution DWIDL offered significantly superior image quality, sharpness, noise, contrast, and diagnostic confidence (each p &lt; 0.02)). Artifacts were significantly higher in DWIDL by one reader (M = 4.62 vs. 4.36 Likert scale, p &lt; 0.01) without affecting the diagnostic confidence. SNR was higher in DWIDL for b 50 and ADC maps (each p = 0.07). Acquisition time was reduced by 22% in DWIDL. The lesion diameters in DWI b 800DL and Std and ADCDL and Std were respectively 6% lower compared to the 2nd SUB. A DL-based diffusion sequence at 1.5 T in breast MRI offers a higher resolution and a faster acquisition, including only minimally more artefacts without affecting the diagnostic confidence.