julilili42/papers huggingface dataset:
Prospective Evaluation of a Tumor Control Probability Model Based on Dynamic 18F-FMISO PET for Head and Neck Cancer Radiotherapy
2019-05-10

Our purpose was to evaluate an imaging parameter-response relationship between the extent of tumor hypoxia quantified by dynamic <sup>18</sup>F-fluoromisonidazole (<sup>18</sup>F-FMISO) PET/CT and the risk of relapse after radiotherapy in patients with head and neck cancer. <b>Methods:</b> Before a prospective cohort of 25 head and neck cancer patients started radiotherapy, they were examined with dynamic <sup>18</sup>F-FMISO PET/CT 0-240 min after tracer injection. <sup>18</sup>F-FMISO image parameters, including a hypoxia metric, <i>M</i><sub><i>FMISO</i></sub><i>,</i> derived from pharmacokinetic modeling of dynamic <sup>18</sup>F-FMISO and maximum tumor-to-muscle ratio (TMR<sub>max</sub>) at 4 h after injection, gross tumor volume (GTV), relative hypoxic volume based on <i>M</i><sub><i>FMISO</i></sub><i>,</i> and a logistic regression model combining GTV and TMR<sub>max</sub>, were assessed and compared with a previous training cohort (<i>n</i> = 15). Dynamic <sup>18</sup>F-FMISO was used to validate a tumor control probability model based on <i>M</i><sub><i>FMISO</i></sub> The prognostic potential with respect to local control of all potential parameters was validated using the concordance index for univariate Cox regression models determined from the training cohort, in addition to Kaplan-Meier analysis including the log-rank test. <b>Results:</b> The tumor control probability model was confirmed, indicating that dynamic <sup>18</sup>F-FMISO allows stratification of patients into different risk groups according to radiotherapy outcome. In this study, <i>M</i><sub><i>FMISO</i></sub> was the only parameter that was confirmed as prognostic in the independent validation cohort (concordance index, 0.71; <i>P</i> = 0.004). All other investigated parameters, such as TMR<sub>max</sub>, GTV, relative hypoxic volume, and the combination of GTV and TMR<sub>max</sub>, were not able to stratify patient groups according to outcome in this validation cohort (<i>P</i> = not statistically significant). <b>Conclusion:</b> In this study, the relationship between <i>M</i><sub><i>FMISO</i></sub> and the risk of relapse was prospectively validated. The data support further evaluation and external validation of dynamic <sup>18</sup>F-FMISO PET/CT as a promising method for patient stratification and hypoxia-based radiotherapy personalization, including dose painting.
Refining the Spectrum of Neuronal Intranuclear Inclusion Disease: A Case Report
2019-05-10

Neuronal intranuclear inclusion disease (NIID) is a rare heterogeneous progressive neurodegenerative disease characterized by the presence of eosinophilic hyaline intranuclear inclusions in neuronal and glial cells of the CNS, peripheral cells of the autonomic nervous system, visceral organs and skin. The clinical presentation is broadly heterogeneous and includes limb weakness, dementia, seizures, ataxia, and parkinsonism. High-intensity signal in the corticomedullary junction on brain MRI is a characteristic finding in NIID. We describe a 65-year-old patient presenting with mild cognitive impairment, evolving in dementia with behavioral disturbances and parkinsonism. Brain MRI showed mild global cortical atrophy, more pronounced in the cingulate and temporal cortex and mild leukoaraiosis, but no high-intensity signal in corticomedullary junction on diffusion weighted imaging. Neuropathological examination showed p62- and optineurin-positive neuronal intranuclear inclusions in the hippocampus and in some subcortical structures. Glial cells did not present any intranuclear inclusions, and no spongiotic changes proximal to the U-fibers or diffuse myelin pallor were disclosed in the white matter. We report on a case with pathological features of NIID showing different neuroimaging and pathological findings. We noted an absence of typical MRI abnormalities, lack of intranuclear inclusions in glial cells, and prominent involvement of hippocampal neurons, refining the clinico-pathological spectrum of the disease.
Weighted elastic net for unsupervised domain adaptation with application to age prediction from DNA methylation data
2019-05-10

Abstract Motivation Predictive models are a powerful tool for solving complex problems in computational biology. They are typically designed to predict or classify data coming from the same unknown distribution as the training data. In many real-world settings, however, uncontrolled biological or technical factors can lead to a distribution mismatch between datasets acquired at different times, causing model performance to deteriorate on new data. A common additional obstacle in computational biology is scarce data with many more features than samples. To address these problems, we propose a method for unsupervised domain adaptation that is based on a weighted elastic net. The key idea of our approach is to compare dependencies between inputs in training and test data and to increase the cost of differently behaving features in the elastic net regularization term. In doing so, we encourage the model to assign a higher importance to features that are robust and behave similarly across domains. Results We evaluate our method both on simulated data with varying degrees of distribution mismatch and on real data, considering the problem of age prediction based on DNA methylation data across multiple tissues. Compared with a non-adaptive standard model, our approach substantially reduces errors on samples with a mismatched distribution. On real data, we achieve far lower errors on cerebellum samples, a tissue which is not part of the training data and poorly predicted by standard models. Our results demonstrate that unsupervised domain adaptation is possible for applications in computational biology, even with many more features than samples. Availability and implementation Source code is available at https://github.com/PfeiferLabTue/wenda. Supplementary information Supplementary data are available at Bioinformatics online.
PSM Peptides From Community-Associated Methicillin-Resistant Staphylococcus aureus Impair the Adaptive Immune Response via Modulation of Dendritic Cell Subsets in vivo
2019-05-10

Dendritic cells (DCs) are key players of the immune system and thus a target for immune evasion by pathogens. We recently showed that the virulence factors phenol-soluble-modulins (PSMs) produced by community-associated methicillin-resistant <i>Staphylococcus aureus</i> (CA-MRSA) strains induce tolerogenic DCs upon Toll-like receptor activation via the p38-CREB-IL-10 pathway <i>in vitro</i>. Here, we addressed the hypothesis that <i>S. aureus</i> PSMs disturb the adaptive immune response via modulation of DC subsets <i>in vivo</i>. Using a systemic mouse infection model we found that <i>S. aureus</i> reduced the numbers of splenic DC subsets, mainly CD4<sup>+</sup> and CD8<sup>+</sup> DCs independently of PSM secretion. <i>S. aureus</i> infection induced upregulation of the C-C motif chemokine receptor 7 (CCR7) on the surface of all DC subsets, on CD4<sup>+</sup> DCs in a PSM-dependent manner, together with increased expression of MHCII, CD86, CD80, CD40, and the co-inhibitory molecule PD-L2, with only minor effects of PSMs. Moreover, PSMs increased IL-10 production in the spleen and impaired TNF production by CD4<sup>+</sup> DCs. Besides, <i>S. aureus</i> PSMs reduced the number of CD4<sup>+</sup> T cells in the spleen, whereas CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> regulatory T cells (T<sub>regs</sub>) were increased. In contrast, Th1 and Th17 priming and IFN-γ production by CD8<sup>+</sup> T cells were impaired by <i>S. aureus</i> PSMs. Thus, PSMs from highly virulent <i>S. aureus</i> strains modulate the adaptive immune response in the direction of tolerance by affecting DC functions.
ParkinSong: A Controlled Trial of Singing-Based Therapy for Parkinson’s Disease
2019-05-12

Background. Communication impairment is one of the most common symptoms of Parkinson’s disease (PD), significantly affecting quality of life. Singing shares many of the neural networks and structural mechanisms used during speech and, thus, has potential for therapeutic application to address speech disorders. Objective. To explore the effects of an interdisciplinary singing-based therapeutic intervention (ParkinSong) on voice and communication in people with PD. Methods. A controlled trial compared the effects of the ParkinSong intervention with an active control condition at 2 dosage levels (weekly vs monthly) over 3 months, on voice, speech, respiratory strength, and voice-related quality-of-life outcomes for 75 people living with PD. The interdisciplinary ParkinSong model comprised high-effort vocal and respiratory tasks, speech exercises, group singing, and social communication opportunities. Results. ParkinSong intervention participants demonstrated significant improvements in vocal intensity ( P = .018), maximum expiratory pressure ( P = .032), and voice-related quality of life ( P = .043) in comparison to controls. Weekly ParkinSong participants increased vocal intensity more than monthly participants ( P = .011). Vocal intensity declined in nontreatment control groups. No statistical differences between groups on maximum phonation length or maximum inspiratory pressure were observed at 3 months. Conclusions. ParkinSong is an engaging intervention with the potential to increase loudness and respiratory function in people with mild to moderately severe PD.
Prenatal liver stromal cells: Favorable feeder cells for long‐term culture of hepatic progenitor cells
2019-05-12

Abstract Clinical and pharmaceutical applications of primary hepatocytes (PHs) are limited due to inadequate number of donated livers and potential challenges in successful maintenance of PHs in culture. Freshly isolated hepatocytes lose their specific features and rapidly de‐differentiate in culture. Bipotent hepatoblasts, as liver precursor cells that can differentiate into both hepatocytes and cholangiocytes (Alb‐ and Ck19‐positive cells, respectively), could be used as an alternative and reliable cell source to produce enough PHs for drug discovery or possible clinical applications. In this study, growth factor‐free coculture systems of prenatal or postnatal murine liver stromal cells (pre‐LSCs or post‐LSCs, respectively) were used as feeder cells to support freshly isolated mice hepatoblasts. DLK1‐positive hepatoblasts were isolated from mouse fetuses (E14.5) and cocultured with feeder cells under adherent conditions. The hepatoblasts' bipotent features, proliferation rate, and colony formation capacity were assessed on day 5 and 7 post‐seeding. Immunofluorescence staining showed that the hepatoblasts remained double positive for Alb and Ck19 on both Pre‐ and Post‐LSCs, after 5 and 7 days of coculture. Moreover, application of pre‐LSCs as feeder cells significantly increased the number of DLK1‐positive cells and their proliferation rate (ie, increased the number of Ki‐67 positive cells) on day 7, compared to Post‐LSCs group. Finally, to address our ultimate goal, which was an extension of hepatoblasts ex vivo maintenance, 3D spheres of isolated hepatoblasts were, cultured in conditioned medium (CM) derived from pre‐LSCs until day 30. It was observed that the CM derived from Pre‐LSCs could successfully prolong the maintenance of hepatic progenitor cells (HPCs) in 3D suspension culture.
Retrospective correction of motion‐affected MR images using deep learning frameworks
2019-05-13

Purpose Motion is 1 extrinsic source for imaging artifacts in MRI that can strongly deteriorate image quality and, thus, impair diagnostic accuracy. In addition to involuntary physiological motion such as respiration and cardiac motion, intended and accidental patient movements can occur. Any impairment by motion artifacts can reduce the reliability and precision of the diagnosis and a motion‐free reacquisition can become time‐ and cost‐intensive. Numerous motion correction strategies have been proposed to reduce or prevent motion artifacts. These methods have in common that they need to be applied during the actual measurement procedure with a‐priori knowledge about the expected motion type and appearance. For retrospective motion correction and without the existence of any a‐priori knowledge, this problem is still challenging. Methods We propose the use of deep learning frameworks to perform retrospective motion correction in a reference‐free setting by learning from pairs of motion‐free and motion‐affected images. For this image‐to‐image translation problem, we propose and compare a variational auto encoder and generative adversarial network. Feasibility and influences of motion type and optimal architecture are investigated by blinded subjective image quality assessment and by quantitative image similarity metrics. Results We observed that generative adversarial network‐based motion correction is feasible producing near‐realistic motion‐free images as confirmed by blinded subjective image quality assessment. Generative adversarial network‐based motion correction accordingly resulted in images with high evaluation metrics (normalized root mean squared error &lt;0.08, structural similarity index &gt;0.8, normalized mutual information &gt;0.9). Conclusion Deep learning‐based retrospective restoration of motion artifacts is feasible resulting in near‐realistic motion‐free images. However, the image translation task can alter or hide anatomical features and, therefore, the clinical applicability of this technique has to be evaluated in future studies.
Langerhans Cells Sense Staphylococcus aureus Wall Teichoic Acid through Langerin To Induce Inflammatory Responses
2019-05-13

The bacterium Staphylococcus aureus is an important cause of skin infections and is also associated with the occurrence and severity of eczema. Langerhans cells (LCs), a specific subset of skin immune cells, participate in the immune response to S. aureus , but it is yet unclear how LCs recognize S. aureus . Therefore, we investigated the molecular mechanism underlying the interaction between LCs and S. aureus . We identified that wall teichoic acid, an abundant polymer on the S. aureus surface, is recognized by langerin, a receptor unique to LCs. This interaction allows LCs to discriminate S. aureus from other related staphylococcal species and initiates a proinflammatory response similar to that observed in patients with eczema. Our data therefore provide important new insights into the relationship between S. aureus , LCs, and eczema.
Individual acquisition of “stick pounding” behavior by naïve chimpanzees
2019-05-13

Abstract Many studies investigating culture in nonhuman animals tend to focus on the inferred need of social learning mechanisms that transmit the form of a behavior to explain the population differences observed in wild animal behavioral repertoires. This research focus often results in studies overlooking the possibility of individuals being able to develop behavioral forms without requiring social learning. The disregard of individual learning abilities is most clearly observed in the nonhuman great ape literature, where there is a persistent claim that chimpanzee behaviors, in particular, require various forms of social learning mechanisms. These special social learning abilities have been argued to explain the acquisition of the relatively large behavioral repertoires observed across chimpanzee populations. However, current evidence suggests that although low‐fidelity social learning plays a role in harmonizing and stabilizing the frequency of behaviors within chimpanzee populations, some (if not all) of the forms that chimpanzee behaviors take may develop independently of social learning. If so, they would be latent solutions—behavioral forms that can (re‐)emerge even in the absence of observational opportunities, via individual (re)innovations. Through a combination of individual and low‐fidelity social learning, the population‐wide patterns of behaviors observed in great ape species are then established and stably maintained. This is the Zone of Latent Solutions (ZLS) hypothesis. The current study experimentally tested the ZLS hypothesis for pestle pounding, a wild chimpanzee behavior. We tested the reinnovation of this behavior in semi‐wild chimpanzees at Chimfunshi Wildlife Orphanage in Zambia, Africa, ( N = 90, tested in four social groups). Crucially, all subjects were naïve to stick pounding before testing. Three out of the four tested groups reinnovated stick pounding—clearly demonstrating that this behavioral form does not require social learning. These findings provide support for the ZLS hypothesis alongside further evidence for the individual learning abilities of chimpanzees.
Inverse problem for Hawking radiation
2019-05-13

In this work we study the inverse problem related to the emission of Hawking\\nradiation. We first show how the knowledge of greybody factors of different\\nangular contributions can be used to constrain the width of the\\ncorresponding black hole perturbation potentials. Afterwards we provide a\\nframework to recover the greybody factors from the actual energy emission\\nspectrum, which has to be treated as sum over all multipole numbers. The\\nunderlying method for the reconstruction of the potential widths is based on\\nthe inversion of the Gamow formula, a parabolic expansion and the\\nP\\\\"oschl-Teller potential. We define a `normalized' energy emission spectrum\\nthat turns out to be very beneficial for the numerical fitting process, as well\\nas for an improved qualitative understanding of how much information of the\\nblack hole potentials are actually imprinted in the spectrum. The connection to\\nrecent studies on the inverse problem using the quasi-normal spectra of ultra\\ncompact stars and exotic compact objects is discussed as well. In the appendix\\nwe show that the spectrum can be approximated surprisingly well and simply with\\na parabolic expansion of the peak of the classical black hole scattering\\npotentials.\\n
The first family group of α1-AT-P in the world with repeated hematomas: 10-year follow-up
2019-05-13

This case report describes the first 10-year follow-up report worldwide of a patient with the genetic variation alpha-1-antitrypsin-Pittsburgh mutation (α1-AT-P). The mutation was confirmed in a 16 year-old Chinese girl after she presented with repeated hematomas, and the mutation with bleeding tendency was also verified in her father. α1-AT-P is a spontaneously occurring autosomal dominant point mutation of α1-antitrypsin, in which methionine-358 is substituted by an arginine derivative. α1-AT-P cases are extremely rare, with only eight reported worldwide. Consequently, there is insufficient experience in the diagnosis and treatment of α1-AT-P. We followed up and reviewed the last 10 years of treatment of a young patient who suffered from repeated life-threatening hematomas, underwent emergency surgery five times, and had her ovaries removed in her twenties to avoid ovulation hemorrhage. The purpose of this article is to raise the awareness of α1-AT-P mutation and to improve its prognosis, especially in female patients.
Interactive impact of childhood maltreatment, depression, and age on cortical brain structure: mega-analytic findings from a large multi-site cohort
2019-05-14

Abstract Background Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age. Methods Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer. Results CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions. Conclusions Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
A large-scale drug screen identifies selective inhibitors of class I HDACs as a potential therapeutic option for SHH medulloblastoma
2019-05-14

Abstract Background Medulloblastoma (MB) is one of the most frequent malignant brain tumors of children, and a large set of these tumors is characterized by aberrant activation of the sonic hedgehog (SHH) pathway. While some tumors initially respond to inhibition of the SHH pathway component Smoothened (SMO), tumors ultimately recur due to downstream resistance mechanisms, indicating a need for novel therapeutic options. Methods Here we performed a targeted small-molecule screen on a stable, SHH-dependent murine MB cell line (SMB21). Comprehensive isotype profiling of histone deacetylase (HDAC) inhibitors was performed, and effects of HDAC inhibition were evaluated in cell lines both sensitive and resistant to SMO inhibition. Lastly, distinct mouse models of SHH MB were used to demonstrate pharmacologic efficacy in vivo. Results A subset of the HDAC inhibitors tested significantly inhibit tumor growth of SMB21 cells by preventing SHH pathway activation. Isotype profiling of HDAC inhibitors, together with genetic approaches suggested that concerted inhibition of multiple class I HDACs is necessary to achieve pathway inhibition. Of note, class I HDAC inhibitors were also efficacious in suppressing growth of diverse SMO inhibitor‒resistant clones of SMB21 cells. Finally, we show that the novel HDAC inhibitor quisinostat targets multiple class I HDACs, is well tolerated in mouse models, and robustly inhibits growth of SHH MB cells in vivo as well as in vitro. Conclusions Our data provide strong evidence that quisinostat or other class I HDAC inhibitors might be therapeutically useful for patients with SHH MB, including those resistant to SMO inhibition.