julilili42/papers huggingface dataset:
Mental disorders are no predictors to determine the duration of cannabis-based treatment for chronic pain
2023-01-06

Background Chronic pain (CP), a complex biopsychosocial disorder with a global prevalence of up to 33%, can be treated by following multidisciplinary approaches that may include cannabis-based medicine (CBM). However, because CBM continues to be a new treatment, questions remain regarding the ideal duration for CBM and its psychosocial determinants, including mental comorbidities. Methods In a retrospective cross-sectional study involving 46 patients with CP (ICD-10 code F45.4-), three validated instruments—the German Pain Questionnaire, the Depression Anxiety Stress Scale (DASS), and the Marburg Questionnaire of Habitual WellBeing—were used to identify pain-specific psychosocial determinants and mental disorders. Descriptive analyses, a group differences analysis, and a logistic regression analysis were performed using SPSS. Results The patients most frequently reported low back pain as the primary location of their CP, and in attributing the condition to tissue damage, most had largely adopted a somatic orientation in conceptualizing their illness. Most had experienced CP for more than 5 years ( M = 5.13 years, SD = 1.41) and, as a consequence, faced significant restrictions in their everyday life and exhibited low subjective wellbeing (MFHW median = 4.00, N = 43, Q1: 2.00, Q3: 9.00, range: 0–20). Comorbidities among the patients included depression, (DASS-Depression, median: 11.50, Q1: 7.00, Q3: 16.25), anxiety (DASS-Anxiety, median: 4.50, Q1: 2.75, Q3: 8.00), and stress (DASS-Stress, median: 11.00, Q1: 7.00, Q3: 15.00). Between the two cannabis-based treatments with a course lasting either less or more than a year, the duration of treatment showed no between-group differences in terms of sociodemographic factors, pain-specific factors, conceptualizations of the illness, or mental disorders. Psychosocial determinants such as subjective wellbeing and mental comorbidities were not significant predictors of the duration of cannabis-based treatment. Conclusion We found no evidence indicating that the benefits of short-term vs. long-term cannabis-based treatment can be predicted by mental comorbidities or psychosocial factors. However, because CBM may be included in approaches to treat CP, questions about the ideal duration of such treatment remain to be answered.
GramAdapt Social Contact Dataset
2023-01-06

The GramAdapt Social Contact Dataset is a curated dataset of 34 language pairs from across the globe, with quantitative and qualitative data on social interaction between pairs of language communities in contact. The language pairs were sampled globally, with the intention of avoiding areal and cultural biases. The data were collected by distributing a questionnaire to experts who have experience with either one or both of the language communities. The responses are subjective expert assessments. Authors 1-3 manually checked each response for judgement of responses. This results in a dataset containing 12554 data points.
Reliability, factor structure, and validity of the German version of the Trauma Symptom Checklist for Children in a sample of adolescents
2023-01-06

The Trauma Symptom Checklist for Children (TSC-C) is the most widely used self-report scale to assess trauma-related symptoms in children and adolescents on six clinical scales. The purpose of the present study was to develop a German version of the TSC-C and to investigate its psychometric properties, such as factor structure, reliability, and validity, in a sample of German adolescents. A normative sample of <i>N</i>=583 and a clinical sample of <i>N</i>=41 adolescents with a history of physical or sexual abuse aged between 13 and 21 years participated in the study. The Confirmatory Factor Analysis on the six-factor model (<i>anger</i>, <i>anxiet</i>y, <i>depression</i>, <i>dissociation</i>, <i>posttraumatic stress</i>, and <i>sexual concerns</i> with the subdimensions <i>preoccupation</i> and <i>distress</i>) revealed acceptable to good fit statistics in the normative sample. One item had to be excluded from the German version of the TSC-C because the factor loading was too low. All clinical scales presented acceptable to good reliability, with Cronbach's α's ranging from .80 to .86 in the normative sample and from .72 to .87 in the clinical sample. Concurrent validity was also demonstrated by the high correlations between the TSC-C scales and instruments measuring similar psychopathology. TSC-C scores reliably differentiated between adolescents with trauma history and those without trauma history, indicating discriminative validity. In conclusion, the German version of the TSC-C is a reliable and valid instrument for assessing trauma-related symptoms on six different scales in adolescents aged between 13 and 21 years.
Speech and Nonspeech Parameters in the Clinical Assessment of Dysarthria: A Dimensional Analysis
2023-01-07

Nonspeech (or paraspeech) parameters are widely used in clinical assessment of speech impairment in persons with dysarthria (PWD). Virtually every standard clinical instrument used in dysarthria diagnostics includes nonspeech parameters, often in considerable numbers. While theoretical considerations have challenged the validity of these measures as markers of speech impairment, only a few studies have directly examined their relationship to speech parameters on a broader scale. This study was designed to investigate how nonspeech parameters commonly used in clinical dysarthria assessment relate to speech characteristics of dysarthria in individuals with movement disorders. Maximum syllable repetition rates, accuracies, and rates of isolated and repetitive nonspeech oral–facial movements and maximum phonation times were compared with auditory–perceptual and acoustic speech parameters. Overall, 23 diagnostic parameters were assessed in a sample of 130 patients with movement disorders of six etiologies. Each variable was standardized for its distribution and for age and sex effects in 130 neurotypical speakers. Exploratory Graph Analysis (EGA) and Confirmatory Factor Analysis (CFA) were used to examine the factor structure underlying the diagnostic parameters. In the first analysis, we tested the hypothesis that nonspeech parameters combine with speech parameters within diagnostic dimensions representing domain–general motor control principles. In a second analysis, we tested the more specific hypotheses that diagnostic parameters split along effector (lip vs. tongue) or functional (speed vs. accuracy) rather than task boundaries. Our findings contradict the view that nonspeech parameters currently used in dysarthria diagnostics are congruent with diagnostic measures of speech characteristics in PWD.
Enactive mastery experience improves attitudes towards digital technology via self-efficacy – a pre-registered quasi-experiment
2023-01-07

The purpose of this research is to improve attitudes towards digital technology. To this end, we compared two ways of introducing technology: an enactive mastery versus a vicarious experience. The former aimed at improving employees’ self-efficacy to use a robotic technology and, thereby, their attitudes towards it. We examined three attitude dimensions that are relevant when implementing new technology: (1) technology enthusiasm, (2) resistance to change, and (3) job insecurity. We also tested for self-efficacy as mediator between experience and attitudes. The results of the pre-registered quasi-experiment with operators working in the automotive sector (N = 106) supported our hypothesis: Enactive mastery experience, in which workers actively engaged with the technology, led to a higher technology enthusiasm as compared to vicarious experience. This effect was explained by an increase in self-efficacy. Additional analyses revealed that enactive mastery experience also led to lower resistance to change, but not to lower job insecurity. The findings highlight how organisations can apply a simple, yet effective strategy to successfully implement technology at work and motivate employees to use it. They also reveal self-efficacy as the underlying psychological mechanism of enactive mastery, thereby providing an important starting point for designing interventions in organisations.
BRASSINOSTEROID INSENSITIVE1 internalization can occur independent of ligand binding
2023-01-07

Abstract The brassinosteroid (BR) hormone and its plasma membrane (PM) receptor BR INSENSITIVE1 (BRI1) are one of the best-studied receptor–ligand pairs for understanding the interplay between receptor endocytosis and signaling in plants. BR signaling is mainly determined by the PM pool of BRI1, whereas BRI1 endocytosis ensures signal attenuation. As BRs are ubiquitously distributed in the plant, the tools available to study the BRI1 function without interference from endogenous BRs are limited. Here, we designed a BR binding-deficient Arabidopsis (Arabidopsis thaliana) mutant based on protein sequence-structure analysis and homology modeling of members of the BRI1 family. This tool allowed us to re-examine the BRI1 endocytosis and signal attenuation model. We showed that despite impaired phosphorylation and ubiquitination, BR binding-deficient BRI1 internalizes similarly to the wild type form. Our data indicate that BRI1 internalization relies on different endocytic machineries. In addition, the BR binding-deficient mutant provides opportunities to study non-canonical ligand-independent BRI1 functions.
High-Dose Ascorbate in Combination with Anti-PD1 Checkpoint Inhibition as Treatment Option for Malignant Melanoma
2023-01-07

Ascorbate acts as a prooxidant when administered parenterally at high supraphysiological doses, which results in the generation of hydrogen peroxide in dependence on oxygen. Most cancer cells are susceptible to the emerging reactive oxygen species (ROS). Accordingly, we evaluated high-dose ascorbate for the treatment of the B16F10 melanoma model. To investigate the effects of ascorbate on the B16F10 cell line in vitro, viability, cellular impedance, and ROS production were analyzed. In vivo, C57BL/6NCrl mice were subcutaneously injected into the right flank with B16F10 cells and tumor-bearing mice were treated intraperitoneally with ascorbate (3 g/kg bodyweight), immunotherapy (anti-programmed cell death protein 1 (PD1) antibody J43; 2 mg/kg bodyweight), or both treatments combined. The efficacy and toxicity were analyzed by measuring the respective tumor sizes and mouse weights accompanied by histological analysis of the protein levels of proliferating cell nuclear antigen (Pcna), glucose transporter 1 (Glut-1), and CD3. Treatment of B16F10 melanoma-carrying mice with high-dose ascorbate yielded plasma levels in the pharmacologically effective range, and ascorbate showed efficacy as a monotherapy and when combined with PD1 inhibition. Our data suggest the applicability of ascorbate as an additional therapeutic agent that can be safely combined with immunotherapy and has the potential to potentiate anti-PD1-based immune checkpoint blockades.
Cytokinins regulate spatially-specific ethylene production to control root growth inArabidopsis
2023-01-08

Abstract The two principal growth regulators cytokinins and ethylene are known to interact in the regulation of plant growth. However, information about underlying molecular mechanism and positional specificity of the cytokinin/ethylene crosstalk in root growth control is scarce. We have identified spatial specificity of cytokinin-regulated root elongation and root apical meristem (RAM) size, both of which we demonstrate to be ethylene biosynthesis-dependent. Upregulation of the cytokinin biosynthetic gene ISOPENTENYLTRANSFERASE ( IPT ) in proximal and peripheral tissues leads to both root and RAM shortening. In contrast, IPT activation in distal and inner tissues reduces RAM size while leaving the root length comparable to mock-treated controls. We show that cytokinins regulate two steps specific to ethylene biosynthesis, the production of ACC by ACC SYNTHASEs (ACSs), and its conversion to ethylene by ACC OXIDASEs (ACOs). We describe cytokinin- and ethylene-specific regulation controlling the activity of ACSs and ACOs that are spatially discrete along both proximo/distal and radial root axes. Using direct ethylene measurements, we identify ACO2, ACO3 and ACO4 as being responsible for ethylene biosynthesis and the ethylene-regulated root and RAM shortening in cytokinin-treated Arabidopsis . Finally, we describe the tight cooperation between cytokinin and ethylene signaling in cytokinin-induced, ethylene-regulated control of ACO4 due to the direct interaction between ARABIDOPSIS RESPONSE REGULATOR 2 (ARR2), a member of the multistep phosphorelay cascade and the C-terminal portion of ETHYLENE INSENSITIVE 2 (EIN2-C), a key regulator of canonical ethylene signaling.
Pembrolizumab in combination with nab-paclitaxel for the treatment of patients with early-stage triple-negative breast cancer – A single-arm phase II trial (NeoImmunoboost, AGO-B-041)
2023-01-09

pCR rates after NACT with nP and anthracycline combined with pembrolizumab are encouraging. With acceptable side-effect profiles, this treatment might be a reasonable alternative to platinum-containing chemotherapy in cases of contraindications. However, without data from randomised trials and long-term follow up, platinum/anthracycline/taxane-based chemotherapy remains the standard combination chemotherapy for pembrolizumab.
Bone Healing Gone Wrong: Pathological Fracture Healing and Non-Unions—Overview of Basic and Clinical Aspects and Systematic Review of Risk Factors
2023-01-09

Bone healing is a multifarious process involving mesenchymal stem cells, osteoprogenitor cells, macrophages, osteoblasts and -clasts, and chondrocytes to restore the osseous tissue. Particularly in long bones including the tibia, clavicle, humerus and femur, this process fails in 2–10% of all fractures, with devastating effects for the patient and the healthcare system. Underlying reasons for this failure are manifold, from lack of biomechanical stability to impaired biological host conditions and wound-immanent intricacies. In this review, we describe the cellular components involved in impaired bone healing and how they interfere with the delicately orchestrated processes of bone repair and formation. We subsequently outline and weigh the risk factors for the development of non-unions that have been established in the literature. Therapeutic prospects are illustrated and put into clinical perspective, before the applicability of biomarkers is finally discussed.
Reduced impact of nonverbal cues during integration of verbal and nonverbal emotional information in adults with high-functioning autism
2023-01-09

Background When receiving mismatching nonverbal and verbal signals, most people tend to base their judgment regarding the current emotional state of others primarily on nonverbal information. However, individuals with high-functioning autism (HFA) have been described as having difficulties interpreting nonverbal signals. Recognizing emotional states correctly is highly important for successful social interaction. Alterations in perception of nonverbal emotional cues presumably contribute to misunderstanding and impairments in social interactions. Methods To evaluate autism-specific differences in the relative impact of nonverbal and verbal cues, 18 adults with HFA (14 male and four female subjects, mean age 36.7 years (SD 11.4) and 18 age, gender and IQ-matched typically developed controls [14 m/4 f, mean age 36.4 years (SD 12.2)] rated the emotional state of speakers in video sequences with partly mismatching emotional signals. Standardized linear regression coefficients were calculated as a measure of the reliance on the nonverbal and verbal components of the videos for each participant. Regression coefficients were then compared between groups to test the hypothesis that autistic adults base their social evaluations less strongly on nonverbal information. Further exploratory analyses were performed for differences in valence ratings and response times. Results Compared to the typically developed control group, nonverbal cue reliance was reduced in adults with high-functioning autism [ t (23.14) = −2.44, p = 0.01 (one-sided)]. Furthermore, the exploratory analyses showed a tendency to avoid extreme answers in the HFA group, observable via less positive as well as less negative valence ratings in response to emotional expressions of increasingly strong valence. In addition, response time was generally longer in HFA compared to the control group [ F (1, 33) = 10.65, p = 0.004]. Conclusion These findings suggest reduced impact of nonverbal cues and longer processing times in the analysis of multimodal emotional information, which may be associated with a subjectively lower relevance of this information and/or more processing difficulties for people with HFA. The less extreme answering tendency may indicate a lower sensitivity for nonverbal valence expression in HFA or result from a tendency to avoid incorrect answers when confronted with greater uncertainty in interpreting emotional states.
A Cautionary Note Regarding Multilevel Factor Score Estimates from Lavaan
2023-01-09

To compute factor score estimates, lavaan version 0.6–12 offers the function lavPredict( ) that can not only be applied in single-level modeling but also in multilevel modeling, where characteristics of higher-level units such as working environments or team leaders are often assessed by ratings of employees. Surprisingly, the function provides results that deviate from the expected ones. Specifically, whereas the function yields correct EAP estimates of higher-level factors, the ML estimates are counterintuitive and possibly incorrect. Moreover, the function does not provide the expected standard errors. I illustrate these issues using an example from organizational research where team leaders are evaluated by their employees, and I discuss these issues from a measurement perspective.
Alternative Chemotherapies: Angiotensin-Converting Enzyme Inhibitors Reduce Myeloid-Derived Suppressor Cells to Benefit Older Patients with Colorectal Cancer
2023-01-09

Older individuals are more likely to develop solid cancers, but at the same time are more sensitive to the side effects of chemotherapy. In addition, older adults are more likely to present with chronic diseases (comorbidities) and immunosenescence that may decrease immunosurveillance against cancer. Clinical outcomes for the older patient with cancer are different from the younger patient and require different research and treatment approaches. Thus, alternative therapeutic approaches tailored specifically to the older patients are required. Colorectal cancer (CRC) has a high incidence in older individuals and is the third leading cause of cancer death globally. Anti-hypertensives are used by a large proportion of older patients and some studies have pointed to a positive impact of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) on CRC outcomes. As we have previously shown in a mouse model, lung metastases express ACE and contain many infiltrating myeloid-derived suppressor cells (MDSC); particularly high levels of MDSC are also present in the blood of older patients with CRC and other cancers, and are associated with disease severity. In this Commentary, we hypothesize that one mechanism responsible for the positive impact of ACEi or ARB on the outcome of CRC is the modulation of myeloid cells contributing to their maturation to non-suppressive neutrophils/monocytes and diverting them away from retaining an immature MDSC phenotype.
Insertions and deletions in the hypervariable region of the hepatitis E virus genome in individuals with acute and chronic infection
2023-01-09

Abstract Background and Aims Hepatitis E virus is a major cause of acute hepatitis worldwide and can progress to chronicity in immunocompromised individuals. Various virus–host recombination events have been reported in the hypervariable region of the hepatitis E virus genome, but the patterns of assembly and selection remain unclear. Methods To gain further insight into viral evolution, we assessed the presence of low abundance variants in 16 samples from individuals with acute or chronic infection using a targeted next‐generation sequencing approach. Results In seven samples, different variants with insertions and/or deletions were identified. Among them, eight insertions originating either from human genes or from the hepatitis E virus genome. Five different deletions could be identified. The amino acid composition of sequences with insertions showed a higher frequency of lysine and a lower abundance of proline, and additionally acetylation and ubiquitination sites were more frequent than in hepatitis E virus wild‐type sequences. Conclusions These findings suggest that the nucleotide composition of insertions and sites for post‐translational modification may contribute to recombination events. Although the impact of low‐level hepatitis E virus variants is uncertain, our results highlight the importance of a highly sensitive next‐generation sequencing approach to capture the full diversity of hypervariable region.
Characterizing mixed location hemorrhages/microbleeds with CSF markers
2023-01-09

Objective: Cerebral amyloid angiopathy (CAA) is a common cause of lobar and subarachnoid hemorrhages in the elderly. A diagnosis of CAA requires multiple lobar hemorrhagic lesions (intracerebral hemorrhage and/or cerebral microbleeds) and/or cortical superficial siderosis (cSS). In contrast, hemorrhagic lesions located in the deep structures are the hallmark of hypertensive arteriopathy (HTN-A). They are an exclusion criterion for CAA, and when present with lobar hemorrhagic lesions considered a separate entity: mixed location hemorrhages/microbleeds (MLHs). We compared clinical, radiological, and cerebrospinal fluid (CSF) marker data in patients with CAA, MLH, and Alzheimer’s disease (AD), and healthy controls (HCs) and used it to position MLH in the disease spectrum. Patients and Methods: Retrospective cohort study of consecutive patients with CAA (n = 31), MLH (n = 31), AD (n = 28), and HC (n = 30). Analysis of clinical, radiological, CSF biomarker (Aß42, Aß40, t-tau, and p-tau), and histopathological data in patients each group. Results: cSS was significantly more common in CAA than MLH (45% vs 13%, p = 0.011), and cSS in MLH was associated with intracerebral hemorrhage (ICH) (p = 0.037). Aß42 levels and the Aß42/Aß40 ratio, diagnostic groups followed the order HC &gt; MLH &gt; CAA &gt; AD and the opposite order for t-tau and p-tau. No clear order was apparent forAß40. Aß40 and Aß42 levels as well as the Aß42/Aß40 ratio were lower in both CAA and MLH patients with cSS than in patients without cSS. Aß40 and Aß42 levels were higher in CAA and MLH patients with lacunar infarcts than in those without. Conclusion: Our data suggest that MLH and CAA are mutually not exclusive diagnoses, and are part of a spectrum with variable contributions of both CAA and HTN-A.