julilili42/papers huggingface dataset:
“I just had the feeling that the interval training is more beneficial”: young adults' subjective experiences of physical fitness and the role of training modes
2023-05-15

Objective Compelling evidence has shown that high-intensity interval training (HIIT) is associated with substantial increases in physical fitness. However, little is known about whether and how individuals experience these adaptations over time. The purpose of this study is, therefore, to explore how physically inactive young adults subjectively experience physical fitness and its development as they start to exercise and how these experiences relate to different intensity domains (i.e., moderate and severe) as well as to training modes [i.e., HIIT and moderate intensity continuous training (MICT)] and their sequential administration (i.e., HIIT–MICT and MICT–HIIT). Methods Thirty-one inactive participants completed a 15-week two-period sequential exercise intervention in which they first trained for six weeks in a HIIT or a MICT group and subsequently switched training modes. Interviews using the biographical mapping method were conducted at the end of the intervention to assess participants’ exercise- and fitness-related experiences over the past weeks. To assess experiential patterns, we conducted a reflexive thematic analysis. Results We developed three themes that represent the temporal and processual character of starting to exercise after a prolonged period of inactivity: (1) Inactive young adults are not all the same when starting to exercise; (2) Developing physical fitness is a multi-faceted and individual experience; and (3) Feeling physically fit (or not) fosters large-scale effects. Conclusion Our results show that, in retrospect, participants mostly deemed HIIT to be more effective than MICT. Our findings also emphasize that physical fitness is a complex and subjective experience that manifests in various ways over time. The idiosyncrasy of physical fitness experiences reiterates the necessity for individually tailored exercise prescriptions instead of one-size-fits-all approaches.
Loss of the cyclin kinase inhibitor p27kip1 opens atherapeutic window by deregulating pathway choiceafter DNA double strand breaks
2023-05-15

<title>Abstract</title> Reduced expression of the cyclin kinase inhibitor p27kip1 is found in many human tumors and correlates with inferior prognosis. We tested the importance of p27 loss for the induction of genetic instability in Notch driven cholangiocarcinoma (CCA). Specifically, we asked how loss of p27 interferes with DNA repair pathway choice i.e. non-homologous-end-joining (NHEJ) or homologous recombination (HR). We detected all hallmarks of HR, in p27 deficient cells even though these cells had not undergone DNA replication. This defect in pathway choice depends on a previously unknown interaction of p27 with the RAD17 protein. In a cholangiocarcinoma mouse model loss of p27 greatly accelerated tumor formation but also resulted in a strikingly increased sensitivity against DNA damage response (DDR) targeting agents. We find that 30% of human CCC patients cluster in a group which corresponds to the DDR sensitive phenotype we have identified. In this work we show that the cyclin kinase inhibitor p27kip1 has an essential role in regulating the DNA damage response. This new activity of p27 is necessary to suppress homologous recombination-based DNA repair during the G1 phase. These findings point to a role of DDR targeting drugs in CCA with low levels of p27.
Lipase-mediated detoxification of host-derived antimicrobial fatty acids byStaphylococcus aureus
2023-05-15

Abstract Long-chain fatty acids with antimicrobial properties are abundant on the skin and mucosal surfaces, where they are essential to restrict the proliferation of opportunistic pathogens such as Staphylococcus aureus . These antimicrobial fatty acids (AFAs) elicit bacterial adaptation strategies, which have yet to be fully elucidated. Characterizing the pervasive mechanisms used by S. aureus to resist AFAs could open new avenues to prevent pathogen colonization. Here, we identify the S. aureus lipase Lip2 as a novel resistance factor against AFAs. Lip2 detoxifies AFAs via esterification with cholesterol. This is reminiscent of the activity of the fatty acid-modifying enzyme (FAME), whose identity has remained elusive for over three decades. In vitro , Lip2-dependent AFA-detoxification was apparent during planktonic growth and biofilm formation. Our genomic analysis revealed that prophage-mediated inactivation of Lip2 was more common in blood and nose isolates than in skin strains, suggesting a particularly important role of Lip2 for skin colonization. Accordingly, in a mouse model of S. aureus skin colonization, bacteria were protected from sapienic acid - a human-specific AFA - in a cholesterol- and lipase-dependent manner. These results suggest Lip2 is the long-sought FAME that exquisitely manipulates environmental lipids to promote bacterial growth. Our data support a model in which S. aureus exploits and/or exacerbates lipid disorders to colonize otherwise inhospitable niches.
Research on portfolios in teacher education: a systematic review
2023-05-16

Portfolios are credited with an array of potentials (e.g. to reinforce student teachers' professionalisation). Their use in teacher education has rapidly increased in recent years, particularly because of system-wide implementations. Nevertheless, studies on portfolios have not followed this growth. A systematic review of studies is pending. Hence, this study systematically examines the available portfolio research literature (N = 246 texts), focusing on joint research topics and analyses quantitative empirical effects (e.g. on student teachers' reflexivity) in more depth using vote-counting. Overall, there are many findings on student teachers' perceptions of portfolios, but only a few examine portfolios' quantitative empirical effects. Findings indicate that working with portfolios is likely to increase the level of student teachers' reflective writing. Even though the analysed research provides initial insights into portfolios, their significance (e.g. effects on developing professional knowledge) remains unclear.
Prognostic impact of the post-treatment T cell composition and spatial organization in soft tissue sarcoma patients treated with neoadjuvant hyperthermic radio(chemo)therapy
2023-05-16

Soft tissue sarcomas (STS) form a heterogeneous group of tumors sharing a mesenchymal origin. Despite good local control of the disease, the occurrence of distant metastases often limits survival of STS patients with localized, high-risk tumors of the extremities. Accumulating evidence suggests a central role for the tumor immune microenvironment in determining the clinical outcome and response to therapy. Thus, it has been reported that STS patients with a high immune signature and especially presence of B cells and tertiary lymphoid structures display improved overall survival and response to checkpoint inhibitor treatment. Here, we explored the effect of curative multimodal therapy on the T cell landscape of STS using multiplex immunohistochemistry. We analyzed the phenotype, frequency, and spatial distribution of STS-infiltrating CD8 + T cells by staining for CD8, 4-1BB, Granzyme B, Ki67, PD-1, and LAG-3 as well as CD3 + T helper cells using a panel consisting of CD3, T-bet, GATA3, RORγT, FoxP3, and Ki67. All patients received neoadjuvant radiotherapy plus locoregional hyperthermia with or without chemotherapy. While the treatment-naïve biopsy sample allows an analysis of baseline T cell infiltration levels, both intra- and peritumoral areas of the matched resected tissue were analyzed to assess composition and spatial distribution of the T cell compartment and its therapeutic modulation. Generally, post-treatment tissues displayed lower frequencies of CD3 + and CD8 + T cells. Association with clinical data revealed that higher post-treatment frequencies of peritumoral and intratumoral CD3 + T cells and intratumoral PD-1 + CD8 + T cells were significantly associated with improved disease-free survival (DFS), while these densities had no prognostic significance in the biopsy. Upon spatial analysis, a high ratio of intratumoral to peritumoral CD8 + T cells emerged as an independent prognostic marker for longer DFS. These results indicate that the STS T cell landscape is altered by multimodal therapy and may influence the clinical outcome of patients. An enhanced understanding of the STS immune architecture and its modulation by neoadjuvant therapy may pave the way towards novel treatment modalities and improve the long-term clinical outcome of STS patients.
Late Weichselian–Holocene valley development of the Elbe valley near Dresden – linking sedimentation, soil formation and archaeology
2023-05-16

Abstract. Valley infills are essential for understanding changes in hydrology and landscape. Anthropogenic activities are proven by prehistoric settlement remains, which mark distinct sediments and soils as usable land during certain time periods. In 2009 and 2018/19, excavations by the Saxonian Archaeological Heritage Office were conducted in the Elbe valley between Meißen and Dresden, preceding the construction of two natural gas pipelines. As a result, two important multicultural prehistoric sites were discovered on the Lower Weichselian Terrace (LWT) in different sediments and on varying stratigraphic levels. During this study sediments and soils at the excavation sites and throughout the pipe trench have been documented. Micromorphological, sedimentological and geochemical investigations and analyses of archaeobotanical and archaeological finds, complemented by 14C and optically stimulated luminescence (OSL) dating, enabled deciphering the structure of sediments and soils. Two major sites were the focus. At the Clieben site, an early Neolithic settlement and former topsoil, developed in a Weichselian valley loam above gravels and sands, are covered by younger overbank fines. At the Brockwitz site, shallow incision channels in the LWT were filled with clayey overbank fines during the Preboreal. An overprinting humic soil horizon was later anthropogenically overprinted during the early and middle Neolithic period. An omnipresent layer of Subboreal or younger overbank fines, covering the majority of the LWT in combination with the spatially confined Preboreal overbank fines, mirrors the ever-growing risk of flooding in a formerly attractive settlement area.
Polygenic risk scores validated in patient-derived cells stratify for mitochondrial subtypes of Parkinson’s disease
2023-05-16

Abstract Background Parkinson’s disease (PD) is the fastest growing neurodegenerative disorder, with affected individuals expected to double during the next 20 years. This raises the urgent need to better understand the genetic architecture and downstream cellular alterations underlying PD pathogenesis, in order to identify more focused therapeutic targets. While only ∼10% of PD cases can be clearly attributed to monogenic causes, there is mounting evidence that additional genetic factors could play a role in idiopathic PD (iPD). In particular, common variants with low to moderate effect size in multiple genes regulating key neuroprotective activities may act as risk factors for PD. In light of the well-established involvement of mitochondrial dysfunction in PD, we hypothesized that a fraction of iPD cases may harbour a pathogenic combination of common variants in nuclear-encoded mitochondrial genes, ultimately resulting in neurodegeneration. Methods to capture this mitochondria-related “missing heritability”, we leveraged on existing data from previous genome-wide association studies (GWAS) – i.e., the large PD GWAS from Nalls and colleagues. We then used computational approaches based on mitochondria-specific polygenic risk scores (mitoPRSs) for imputing the genotype data obtained from different iPD case-control datasets worldwide, including the Luxembourg Parkinson’s Study (412 iPD patients and 576 healthy controls) and the COURAGE-PD cohorts (7270 iPD cases and 6819 healthy controls). Results applying this approach to gene sets controlling mitochondrial pathways potentially relevant for neurodegeneration in PD, we demonstrated that common variants in genes regulating Oxidative Phosphorylation (OXPHOS -PRS ) were significantly associated with a higher PD risk both in the Luxembourg Parkinson’s Study (odds ratio, OR=1.31[1.14-1.50], p =5.4e-04) and in COURAGE-PD (OR=1.23[1.18-1.27], p =1.5e-29). Functional analyses in primary skin fibroblasts and in the corresponding induced pluripotent stem cells-derived neuronal progenitor cells from Luxembourg Parkinson’s Study iPD patients stratified according to the OXPHOS -PRS, revealed significant differences in mitochondrial respiration between high and low risk groups ( p &lt; 0.05). Finally, we also demonstrated that iPD patients with high OXPHOS -PRS have a significantly earlier age at disease onset compared to low-risk patients. Conclusions our findings suggest that OXPHOS-PRS may represent a promising strategy to stratify iPD patients into pathogenic subgroups – in which the underlying neurodegeneration is due to a genetically defined mitochondrial burden – potentially eligible for future, more tailored mitochondrially targeted treatments.
On the relevance and learner dependence of co-text complexity for exercise difficulty
2023-05-16

Adaptive exercise sequencing in Intelligent Language Tutoring Systems (ILTS) aims to select exercises for individual learners that match their abilities. For exercises practicing forms in isolation, it may be sufficient for sequencing to consider the form being practiced. But when exercises embed the forms in a sentence or bigger language context, little is known about how the nature of this co-text influences learners in completing the exercises. To fill the gap, based on data from two large field studies conducted with an English ILTS in German secondary schools, we analyze the impact of co-text complexity on learner performance for different exercise types and learners at different proficiency levels. The results show that co-text complexity is an important predictor for a learner’s performance on practice exercises, especially for gap filling and Jumbled Sentences exercises, and particularly for learners at higher proficiency levels.
Case report: Interdisciplinary treatment of complex C1/C2 fractures in a patient with concomitant three-vessel coronary artery disease requiring bypass surgery
2023-05-16

Background Acute myocardial infarction (MI) frequently leads to consciousness disturbance following hemodynamic collapse. Therefore, MI can occur together with upper cervical spine trauma. Herein, we report the successful treatment of complex C1/C2 fractures in a patient with concomitant three-vessel coronary artery disease (CAD). Case presentation A 70-year-old patient presented in our emergency outpatient clinic after a hemodynamic collapse without neurological deficits or heart-related complaints. Computed tomography (CT) scan of the cervical spine revealed a dislocated odontoid fracture Anderson and D'Alonzo type II and an unstable Gehweiler type III injury (Jefferson's fracture). An intradiploic arachnoid cyst in the posterior wall of the posterior fossa was a coincident radiological finding. Furthermore, coronary angiography confirmed three-vessel CAD with high-grade coronary artery stenosis. Indication for upper cervical spine surgery and bypass surgery was given. An interdisciplinary team of neurosurgeons, cardiothoracic surgeons and anesthesiologists evaluated the patient's case to develop the most suitable therapy concept and alternative strategies. Finally, in first step, C1-C2 fusion was performed by Harms technique under general anesthesia with x-ray guidance, spinal neuronavigation, Doppler ultrasound and cardiopulmonary monitoring. Cardiothoracic surgeons were on standby. One month later bypass surgery was performed uneventfully. Follow-up CT scan of cervical spine revealed intraosseous screw positioning and beginning fusion of the fractures. The patient did not develop neurological deficits and recovered completely from both surgeries. Conclusions Treating complex C1/C2 fractures with concomitant severe CAD requiring treatment is challenging and carries a high risk of complications. To our knowledge, the literature does not provide any guidelines regarding therapy of this constellation. To receive upper cervical spine stability and to prevent both, spinal cord injury and cardiovascular complications, an individual approach is required. Interdisciplinary cooperation to determine optimal therapeutic algorithms is needed.
Protective Effect of Combined Metoprolol and Atractylenolide I in Rats with Acute Myocardial Infarction via Modulation of the SIRT3/β-CATENIN/PPAR-γ Signaling Pathway
2023-05-16

ABSTRACT Herein, we examined the protective effect of metoprolol combined with atractylenolide I (Atr I) in acute myocardial infarction (AMI) by regulating the SIRT3 (silent information regulator 3)/β-catenin/peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling pathway. Briefly, 50 rats were randomly divided into the sham operation, model, metoprolol, Atr I, and combination metoprolol with Atr I groups (combined treatment group). The AMI model was established by ligating the left anterior descending coronary artery. After treatment, infarct size, histopathological changes, and cell apoptosis were examined using 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, and the TUNEL assay. The left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), and left ventricular mass index (LVMI) were detected by echocardiography. Endothelin-1 (ET-1), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels were detected using enzyme-linked immunosorbent assays. Furthermore, we measured lactate dehydrogenase (LDH), creatine kinase (CK) isoenzyme (CK-MB), and CK levels. Western blotting was performed to determine the expression of SIRT3, β-catenin, and PPAR-γ. Herein, the combined treatment group exhibited increased levels of LVEF, LVFS, and NO, whereas LVMI, ET-1, TNF-α, IL-6, LDH, CK-MB, and CK levels were decreased. Importantly, the underlying mechanism may afford protection against AMI by increasing the expression levels of SIRT3, β-catenin, and PPAR-γ.
Microbial peptides activate tumour-infiltrating lymphocytes in glioblastoma
2023-05-17

Abstract Microbial organisms have key roles in numerous physiological processes in the human body and have recently been shown to modify the response to immune checkpoint inhibitors 1,2 . Here we aim to address the role of microbial organisms and their potential role in immune reactivity against glioblastoma. We demonstrate that HLA molecules of both glioblastoma tissues and tumour cell lines present bacteria-specific peptides. This finding prompted us to examine whether tumour-infiltrating lymphocytes (TILs) recognize tumour-derived bacterial peptides. Bacterial peptides eluted from HLA class II molecules are recognized by TILs, albeit very weakly. Using an unbiased antigen discovery approach to probe the specificity of a TIL CD4 + T cell clone, we show that it recognizes a broad spectrum of peptides from pathogenic bacteria, commensal gut microbiota and also glioblastoma-related tumour antigens. These peptides were also strongly stimulatory for bulk TILs and peripheral blood memory cells, which then respond to tumour-derived target peptides. Our data hint at how bacterial pathogens and bacterial gut microbiota can be involved in specific immune recognition of tumour antigens. The unbiased identification of microbial target antigens for TILs holds promise for future personalized tumour vaccination approaches.
Modulation of dorsal premotor cortex differentially influences I‐wave excitability in primary motor cortex of young and older adults
2023-05-17

Abstract Previous research using transcranial magnetic stimulation (TMS) has demonstrated weakened connectivity between dorsal premotor cortex (PMd) and motor cortex (M1) with age. While this alteration is probably mediated by changes in the communication between the two regions, the effect of age on the influence of PMd on specific indirect (I) wave circuits within M1 remains unclear. The present study therefore investigated the influence of PMd on early and late I‐wave excitability in M1 of young and older adults. Twenty‐two young (mean ± SD, 22.9 ± 2.9 years) and 20 older (66.6 ± 4.2 years) adults participated in two experimental sessions involving either intermittent theta burst stimulation (iTBS) or sham stimulation over PMd. Changes within M1 following the intervention were assessed with motor‐evoked potentials (MEPs) recorded from the right first dorsal interosseous muscle. We applied posterior–anterior (PA) and anterior–posterior (AP) current single‐pulse TMS to assess corticospinal excitability (PA 1mV ; AP 1mV ; PA 0.5mV , early; AP 0.5mV , late), and paired‐pulse TMS short intracortical facilitation for I‐wave excitability (PA SICF, early; AP SICF, late). Although PMd iTBS potentiated PA 1mV and AP 1mV MEPs in both age groups (both P &lt; 0.05), the time course of this effect was delayed for AP 1mV in older adults ( P = 0.001). Furthermore, while AP 0.5mV , PA SICF and AP SICF were potentiated in both groups (all P &lt; 0.05), potentiation of PA 0.5mV was only apparent in young adults ( P &lt; 0.0001). While PMd influences early and late I‐wave excitability in young adults, direct PMd modulation of the early circuits is specifically reduced in older adults. image Key points Interneuronal circuits responsible for late I‐waves within primary motor cortex (M1) mediate projections from dorsal premotor cortex (PMd), but this communication probably changes with advancing age. We investigated the effects of intermittent theta burst stimulation (iTBS) to PMd on transcranial magnetic stimulation (TMS) measures of M1 excitability in young and older adults. We found that PMd iTBS facilitated M1 excitability assessed with posterior–anterior (PA, early I‐waves) and anterior–posterior (AP, late I‐waves) current TMS in young adults, with a stronger effect for AP TMS. M1 excitability assessed with AP TMS also increased in older adults following PMd iTBS, but there was no facilitation for PA TMS responses. We conclude that changes in M1 excitability following PMd iTBS are specifically reduced for the early I‐waves in older adults, which could be a potential target for interventions that enhance cortical excitability in older adults.