julilili42/papers huggingface dataset:
Corticotroph tumor progression after bilateral adrenalectomy (Nelson’s syndrome): systematic review and expert consensus recommendations
2021-01-12

Background Corticotroph tumor progression (CTP) leading to Nelson’s syndrome (NS) is a severe and difficult-to-treat complication subsequent to bilateral adrenalectomy (BADX) for Cushing’s disease. Its characteristics are not well described, and consensus recommendations for diagnosis and treatment are missing. Methods A systematic literature search was performed focusing on clinical studies and case series (≥5 patients). Definition, cumulative incidence, treatment and long-term outcomes of CTP/NS after BADX were analyzed using descriptive statistics. The results were presented and discussed at an interdisciplinary consensus workshop attended by international pituitary experts in Munich on October 28, 2018. Results Data covered definition and cumulative incidence (34 studies, 1275 patients), surgical outcome (12 studies, 187 patients), outcome of radiation therapy (21 studies, 273 patients), and medical therapy (15 studies, 72 patients). Conclusions We endorse the definition of CTP-BADX/NS as radiological progression or new detection of a pituitary tumor on thin-section MRI. We recommend surveillance by MRI after 3 months and every 12 months for the first 3 years after BADX. Subsequently, we suggest clinical evaluation every 12 months and MRI at increasing intervals every 2–4 years (depending on ACTH and clinical parameters). We recommend pituitary surgery as first-line therapy in patients with CTP-BADX/NS. Surgery should be performed before extrasellar expansion of the tumor to obtain complete and long-term remission. Conventional radiotherapy or stereotactic radiosurgery should be utilized as second-line treatment for remnant tumor tissue showing extrasellar extension
Fracture Load of an Orthodontic Appliance for Robin Sequence Treatment in a Digital Workflow
2021-01-12

CAD/CAM technologies and materials have the potential to improve the treatment of Robin Sequence with orthodontic appliances (Tübingen palatal plate, TPP). However, studies on the provided suitability and safety are lacking. The present study evaluates CAD/CAM technologies and materials for implementation into the workflow for producing these orthodontic appliances (TPPs), manufactured by different techniques and materials: additive manufacturing (AM) and subtractive manufacturing (SM) technologies vs. conventional manufacturing. The fracture load was obtained in a universal testing machine, and the breaking behavior of each bunch, as well as the necessity of adding a safety wire, was evaluated. The minimum fracture load was used to calculate the safety factor (SF) provided by each material. Secondary factors included manufacturing time, material cost and reproducibility. Dental LT clear showed the highest fracture load and best breaking behavior among AM materials. The highest fracture load and safety factor were obtained with Smile polyether ether ketone (PEEK). For the prototyping stage, the use of a Freeprint tray (SF = 114.145) is recommended. For final manufacturing, either the cost-effective approach, Dental LT clear (SF = 232.13%), or the safest but most expensive approach, Smile PEEK (SF = 491.48%), can be recommended.
Resting-State Functional Connectivity Disruption as a Pathological Biomarker in Autosomal Dominant Alzheimer Disease
2021-01-12

<b><i>Aim:</i></b> Identify a global resting-state functional connectivity (gFC) signature in mutation carriers (MC) from the Dominantly Inherited Alzheimer Network (DIAN). Assess the gFC with regard to amyloid (A), tau (T), and neurodegeneration (N) biomarkers, and estimated years to symptom onset (EYO). <b><i>Introduction:</i></b> Cross-sectional measures were assessed in MC (<i>n</i> = 171) and mutation noncarrier (NC) (<i>n</i> = 70) participants. A functional connectivity (FC) matrix that encompassed multiple resting-state networks was computed for each participant. <b><i>Methods:</i></b> A global FC was compiled as a single index indicating FC strength. The gFC signature was modeled as a nonlinear function of EYO. The gFC was linearly associated with other biomarkers used for assessing the AT(N) framework, including cerebrospinal fluid (CSF), positron emission tomography (PET) molecular biomarkers, and structural magnetic resonance imaging. <b><i>Results:</i></b> The gFC was reduced in MC compared with NC participants. When MC participants were differentiated by clinical dementia rating (CDR), the gFC was significantly decreased in MC CDR >0 (demented) compared with either MC CDR 0 (cognitively normal) or NC participants. The gFC varied nonlinearly with EYO and initially decreased at EYO = -24 years, followed by a stable period followed by a further decline near EYO = 0 years. Irrespective of EYO, a lower gFC associated with values of amyloid PET, CSF Aβ<sub>1-42</sub>, CSF p-tau, CSF t-tau, 18F-fluorodeoxyglucose, and hippocampal volume. <b><i>Conclusions:</i></b> The gFC correlated with biomarkers used for defining the AT(N) framework. A biphasic change in the gFC suggested early changes associated with CSF amyloid and later changes associated with hippocampal volume.
Histological and Immunohistochemical Changes of Congenital Melanocytic Nevi With Age
2021-01-12

Abstract: Clinical but not histological changes of congenital melanocytic nevi (CMN) with age are well characterized. Our objective was to analyze histological changes of CMN with age and discuss possible clinical implications of our findings. We investigated serial excisions of 21 patients with CMN and compared histological and immunohistochemical features over time. The median number of serial excisions was 6 [interquartile range (IQR) 5–7], the median age at the first excision was 12 months (IQR 5–98), and the median time between the first and last analyzed excision was 53 months (IQR 45–64). The projected adult size of the excised CMN was “large” or “giant” in 14 of the 21 CMN (67%) and “medium” in the remaining lesions (33%). Nineteen CMN (90%) involved the subcutaneous fat, and 16 of the 21 CMN (76%) reached the lower surgical margin. The histological pattern and depth did not change over time but the cellularity and HMB-45 expression of dermal melanocytes decreased in 16 of the 21 patients (76%) and in 15 of the 21 patients (71%), respectively (both P &lt; 0.001). Patients with decreasing HMB-45 expression were significantly younger at the first excision (median 6 months, IQR 4–28) than patients with unchanged HMB-45 expression (median 176 months, IQR 12–186; P = 0.018). The expression of Ki-67 and p16 did not change significantly with age. Our study demonstrates that (1) the cellularity and pigment production of CMN decreases with age, (2) the histological pattern and extension in depth remain stable, and (3) clear resection margins can rarely be achieved in larger CMN.
Exo-β-N-acetylmuramidase NamZ ofBacillus subtilisis the founding member of a family of exo-lytic peptidoglycan hexosaminidases
2021-01-12

ABSTRACT Endo-β- N -acetylmuramidases, commonly known as lysozymes, are well-characterized antimicrobial enzymes that potentially lyse bacterial cells. They catalyze an endo-lytic cleavage of the peptidoglycan, the structural component of the bacterial cell wall; i.e. they hydrolyze glycosidic N -acetylmuramic acid (MurNAc)-β-1,4- N -acetylglucosamine (GlcNAc)-bonds within the heteroglycan backbone of peptidoglycan. In contrast, little is known about exo-β- N -acetylmuramidases, catalyzing an exo-lytic cleavage of β-1,4-MurNAc entities from the non-reducing ends of peptidoglycan chains. Such an enzyme was identified earlier in the bacterium Bacillus subtilis , but the corresponding gene has remained unknown so far. We identified ybbC of B. subtilis, renamed namZ , as encoding the reported exo-β- N -acetylmuramidase. A Δ namZ mutant accumulated specific cell wall fragments and showed growth defects under starvation conditions, indicating a role of NamZ in cell wall turnover. Recombinant NamZ protein specifically hydrolyzed the artificial substrate para-nitrophenyl β-MurNAc and the peptidoglycan-derived disaccharide MurNAc-β-1,4-GlcNAc. Together with the exo-β- N -acetylglucosaminidase NagZ and the exo-muramoyl-L-alanine amidase AmiE, NamZ degraded intact peptidoglycan by sequential hydrolysis from the non-reducing ends. NamZ is a member of the DUF1343 protein family of unknown function and shows no significant sequence identity with known glycosidases. A structural model of NamZ revealed a putative active site located in a cleft within the interface of two subdomains, one of which constituting a Rossmann-fold-like domain, unusual for glycosidases. On this basis, we propose that NamZ represents the founding member of a novel family of peptidoglycan hexosaminidases, which is mainly present in the phylum Bacteroidetes and, less frequently, within Firmicutes (Bacilli, Clostridia), Actinobacteria and Gammaproteobacteria.
Reduced Rate of Inpatient Hospital Admissions in 18 German University Hospitals During the COVID-19 Lockdown
2021-01-13

The COVID-19 pandemic has caused strains on health systems worldwide disrupting routine hospital services for all non-COVID patients. Within this retrospective study, we analyzed inpatient hospital admissions across 18 German university hospitals during the 2020 lockdown period compared to 2018. Patients admitted to hospital between January 1 and May 31, 2020 and the corresponding periods in 2018 and 2019 were included in this study. Data derived from electronic health records were collected and analyzed using the data integration center infrastructure implemented in the university hospitals that are part of the four consortia funded by the German Medical Informatics Initiative. Admissions were grouped and counted by ICD 10 chapters and specific reasons for treatment at each site. Pooled aggregated data were centrally analyzed with descriptive statistics to compare absolute and relative differences between time periods of different years. The results illustrate how care process adoptions depended on the COVID-19 epidemiological situation and the criticality of the disease. Overall inpatient hospital admissions decreased by 35% in weeks 1 to 4 and by 30.3% in weeks 5 to 8 after the lockdown announcement compared to 2018. Even hospital admissions for critical care conditions such as malignant cancer treatments were reduced. We also noted a high reduction of emergency admissions such as myocardial infarction (38.7%), whereas the reduction in stroke admissions was smaller (19.6%). In contrast, we observed a considerable reduction in admissions for non-critical clinical situations, such as hysterectomies for benign tumors (78.8%) and hip replacements due to arthrosis (82.4%). In summary, our study shows that the university hospital admission rates in Germany were substantially reduced following the national COVID-19 lockdown. These included critical care or emergency conditions in which deferral is expected to impair clinical outcomes. Future studies are needed to delineate how appropriate medical care of critically ill patients can be maintained during a pandemic.
Learning by Drawing Visual Representations: Potential, Purposes, and Practical Implications
2021-01-13

The technique of drawing to learn has received increasing attention in recent years. In this article, we will present distinct purposes for using drawing that are based on active, constructive, and interactive forms of engagement. In doing so, we hope to show that drawing to learn should be widely used and that there is good evidence to support its use in many situations. To make the most of these distinct purposes, teachers should note that what learners draw matters and that this needs to be assessed in relation to task demands. Drawing to learn will also require learners to be supported to engage meaningfully in ways that are matched to these pedagogical purposes.
Atomic Layer Deposition of Bioactive TiO2 Thin Films on Polyetheretherketone for Orthopedic Implants
2021-01-13

TiO<sub>2</sub> thin films were deposited on the orthopedic implant material polyetheretherketone (PEEK) by plasma enhanced atomic layer deposition (PEALD) and characterized for their ability to enhance the osseointegrative properties. PEALD was chosen for film deposition to circumvent drawbacks present in line-of-sight deposition techniques, which require technically complex setups for a homogeneous coating thickness. Film conformality was analyzed on silicon 3D test structures and PEEK with micron-scale surface roughness. Wettability and surface energy were determined through contact angle measurements; film roughness and crystallinity were determined by atomic force microscopy and X-ray diffraction, respectively. Adhesion properties of TiO<sub>2</sub> on PEEK were determined with tensile strength tests. Cell tests were performed with the mouse mesenchymal tumor stem cell line ST-2. TiO<sub>2</sub>-coated PEEK disks were used as substrates for cell proliferation tests and long-term differentiation tests. After 28 days of cultivation, a mineralized bone matrix was observed. Furthermore, the collagen I and osteocalcin content were determined. The results reveal that the osteogenic properties of the TiO<sub>2</sub> thin film are comparable to those of hydroxyapatite, and thus bioactive properties of PEEK implants are improved by TiO<sub>2</sub> thin films deposited with PEALD.
Transcriptomics analysis of the metabolic mechanisms of iron reduction induced by sulfate reduction mediated by sulfate-reducing bacteria
2021-01-13

ABSTRACT Sulfate-reducing bacteria (SRB) play an important role in sulfur, iron and carbon cycling. The majority of studies have illustrated the role of SRB in biogeochemical cycling in pure cultures. In this study, we established three SRB enrichment cultures (designated HL, NB and WC) from different paddy soils and conducted a transcriptomic analysis of their metabolic characteristics under sulfate and sulfate-free conditions. In the HL cultures, there was no sulfate consumption but ferrihydrite was reduced. This indicated that bacteria in the HL samples can reduce ferrihydrite and preferentially utilize ferrihydrite as the electron acceptor in the absence of both ferrihydrite and sulfate. Sulfate consumption was equal in the NB and the WC cultures, although more ferrihydrite was reduced in the NB cultures. Transcriptomics analysis showed that (i) upregulation of O-acetylserine sulfhydrylase gene expression indicating sulfate assimilation in the WC samples; (ii) the energy conservation trithionate pathway is commonly employed by SRB and (iii) sulfate not only enhanced iron reduction by its conversion to sulfide but also promoted enzymatic electron transfer via c-type cytochromes.
Differential effects on human cytochromes P450 by CRISPR/Cas9-induced genetic knockout of cytochrome P450 reductase and cytochrome b5 in HepaRG cells
2021-01-13

Abstract HepaRG cells are increasingly accepted as model for human drug metabolism and other hepatic functions. We used lentiviral transduction of undifferentiated HepaRG cells to deliver Cas9 and two alternative sgRNAs targeted at NADPH:cytochrome P450 oxidoreductase (POR), the obligate electron donor for microsomal cytochromes P450 (CYP). Cas9-expressing HepaRG VC (vector control) cells were phenotypically similar to wild type HepaRG cells and could be differentiated into hepatocyte-like cells by DMSO. Genetic POR -knockout resulted in phenotypic POR knockdown of up to 90% at mRNA, protein, and activity levels. LC–MS/MS measurement of seven CYP-activities showed differential effects of POR-knockdown with CYP2C8 being least and CYP2C9 being most affected. Further studies on cytochrome b5 (CYB5), an alternative NADH-dependent electron donor indicated particularly strong support of CYP2C8-dependent amodiaquine N-deethylation by CYB5 and this was confirmed by genetic CYB5 single- and POR/CYB5 double-knockout. POR-knockdown also affected CYP expression on mRNA and protein level, with CYP1A2 being induced severalfold, while CYP2C9 was strongly downregulated. In summary our results show that POR/NADPH- and CYB5/NADH-electron transport systems influence human drug metabolizing CYPs differentially and differently than mouse Cyps. Our Cas9-expressing HepaRG VC cells should be suitable to study the influence of diverse genes on drug metabolism and other hepatic functions.
Using benchtop experiments to teach dimensional analysis and analogue modeling to graduate geoscience students
2021-01-13

The need for geoscience students to develop a quantitative skillset is ever increasing. However, this can be difficult to implement in university-style lecture courses in a way that is both manageable for the instructor and does not involve lengthy, potentially repetitive, question sheets for the students. Here, a method for teaching dimensional analysis, basic fluid dynamics, and the interpretation and scaling of experimental data is presented for a graduate student audience. The proposed method utilizes simple fluid dynamic benchtop experiments that require a small amount of teaching space and use readily available, low cost materials. Our analysis of student performance through pre- and post-tests demonstrates that students have a better knowledge of dimensional analysis, data interpretation and experimental design after the series of practical sessions compared to instruction through a single, passive lecture. We therefore show that simple benchtop experiments can be an effective way to improve and integrate quantitative learning into a graduate geoscience class.
INTEGRAL discovery of a high-energy tail in the microquasar Cygnus X-3
2021-01-13

\\nContext. The X-ray spectra of X-ray binaries are dominated by emission of either soft or hard X-rays which defines their soft and hard spectral states. While the generic picture is relatively well understood, little is known about the interplay of the various media at work, or about the reasons why some sources do not follow common behavior. Cygnus X-3 is amongst the list of X-ray binaries that show quite complex behavior, with various distinct spectral states not seen in other sources. These states have been characterized in many studies. Because of its softness and intrinsic low flux above typically 50 keV, very little is known about the hard X/soft gamma-ray (100–1000 keV) emission in Cygnus X-3.\\nAims. Using the whole INTEGRAL data base, we aim to explore the 3–1000 keV spectra of Cygnus X-3. This allows to probe this region with the highest sensitivity ever, and search for the potential signature of a high-energy non-thermal component as sometimes seen in other sources.\\nMethods. Our work is based on state classification carried out in previous studies with data from the Rossi X-Ray Timing Explorer. We extend this classification to the whole INTEGRAL data set in order to perform a long-term state-resolved spectral analysis. Six stacked spectra were obtained using 16 years of data from JEM-X (3–25 keV), ISGRI (25–300 keV), and SPI (20–400 keV).\\nResults. We extract stacked images in three different energy bands, and detect the source up to 200 keV. In the hardest states, our purely phenomenological approach clearly reveals the presence of an additonnal component &gt; 50 keV in addition to the component usually interpreted as thermal Comptonization. We apply a more physical model of hybrid thermal/nonthermal corona (<sc>EQPAIR</sc>) to characterize this nonthermal component and compare our results with those of previous studies and analyses. Our modeling indicates a more efficient acceleration of electrons in states where major ejections are observed. We also evaluate and find a dependence of the photon index of the power law as a function of the strong orbital modulation of the source in the Flaring InterMediate state. This dependence could be due to a higher absorption when Cygnus X-3 is behind its companion. However, the uncertainties on the density column prevent us from drawing any firm conclusions.\\n
Clinical Presentation and Incidence of Anaerobic Bacteria in Surgically Treated Biliary Tract Infections and Cholecystitis
2021-01-13

(1) Background: Cholecystitis and cholangitis are among the most common diseases treated by general surgery. Gallstones lead to inflammation and bacterial infection of the biliary tract. Biliary infections can lead to live threatening bacteremia and liver abscesses. The true role of anaerobes remains unclear. (2) Methods: We retrospectively analyzed bacterial cultures from biliary samples obtained from bile ducts and gallbladders at our tertiary care center. Patient characteristics and clinical outcomes were analyzed. (3) Results: In our database of 1719 patients, 365 patients had microbial testing, of which 42 grew anaerobic bacteria. Anaerobes were more frequently cultured in patients with hepatic abscesses and gallbladder perforation. These patients were older and had more comorbidities than the control group. The overall outcomes of all patients were favorable and the resistance rate to commonly used antibiotics remained low. (4) Conclusions: Anaerobes in biliary tract infections appear to be underdiagnosed and more prevalent in the elderly with advanced disease. Due to low antibiotic resistance, the combination of source control and adjunct anti-infective treatment leads to favorable outcomes.
Periodic Fluorescence Variations of CdSe Quantum Dots Coupled to Aryleneethynylenes with Aggregation-Induced Emission
2021-01-13

CdSe nanocrystals and aggregates of an aryleneethynylene derivative are assembled into a hybrid thin film with dual fluorescence from both fluorophores. Under continuous excitation, the nanocrystals and the molecules exhibit anticorrelated fluorescence intensity variations, which become periodic at low temperature. We attribute this to a structure-dependent aggregation-induced emission of the aryleneethynylene derivative, which impacts the rate of excitation energy transfer between the molecules and nanocrystals. This work highlights that combining semiconductor nanocrystals with molecular aggregates, which exhibit aggregation-induced emission, can result in emerging optical properties.
HESS J1858+020: A GeV-TeV source possibly powered by cosmic rays from SNR G35.6-0.4
2021-01-13

Context. The supernova remnant (SNR) G35.6−0.4 shows a non-thermal radio shell, however, no γ -ray or X-ray counterparts have been found for it thus far. One TeV source, HESS J1858+020, was found near the SNR and this source is spatially associated with some clouds at 3.6 kpc. Aims. To attain a better understanding of the origin of HESS J1858+020, we further investigate the association between SNR cosmic rays (CRs) and the clouds through the Fermi -LAT analysis and hadronic modeling. Methods. We performed the Fermi -LAT analysis to explore the GeV emission in and around the SNR. We explored the SNR physics with previously observed multi-wavelength data. We built a hadronic model using runaway CRs of the SNR to explain the GeV-TeV observation. Results. We found a hard GeV source (SrcX2) that is spatially coincident with both HESS J1858+020 and a molecular cloud complex at 3.6 kpc. In addition, a soft GeV source (SrcX1) was found at the northern edge of the SNR. The GeV spectrum of SrcX2 connects well with the TeV spectrum of HESS J1858+020. The entire γ -ray spectrum ranges from several GeV up to tens of TeV and it follows a power-law with an index of ~2.15. We discuss several pieces of observational evidence to support the middle-aged SNR argument. Using runaway CRs from the SNR, our hadronic model explains the GeV-TeV emission at HESS J1858+020, with a diffusion coefficient that is much lower than the Galactic value.