Miracle-dz/UniFAR-FTUs huggingface dataset:
[Updated incidence of dry eye syndrome in Germany].

BACKGROUND Dry eye is one of the most common eye surface disorders. Patients suffer in particular from annoying subjective symptoms that compromise quality of life. The aim of the study was to find out when patients consult ophthalmologists in Germany and what symptoms they present. PATIENTS/MATERIAL AND METHODS 170 patients treated at ophthalmological practices in Bavaria, Saxony and Saxony-Anhalt with dry eye were surveyed regarding their symptoms. RESULTS The majority of those questioned were 40 years of age or older (88 %) (average: 60), female (59 %) and described a variety of subjective symptoms (65 %). More than five different concurrent symptoms were named. There is a recognisable increase in cases - by more than 3.5 times - at the age of forty (in women) and fifty (in men). CONCLUSIONS We hope to contribute with the data obtained to a more complete understanding of this highly complex pathological process. A further aim is to facilitate recognition of this mostly chronic condition in its early stages when the symptoms are still poorly defined. The data on the German population obtained here should become part of a comparative analysis within the international context. Despite considerable scientific effort, dry eye remains a difficult challenge for both patients and attending physicians.
Oxidative stress‐induced phosphorylation, degradation and aggregation of α‐synuclein are linked to upregulated CK2 and cathepsin D

Intracellular accumulation of α‐synuclein (α‐Syn) as filamentous aggregates is a pathological feature shared by Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, referred to as synucleinopathies. To understand the mechanisms underlying α‐Syn aggregation, we established a tetracycline‐off inducible transfectant (3D5) of neuronal lineage overexpressing human wild‐type α‐Syn. α‐Syn aggregation was initiated by exposure of 3D5 cells to FeCl2. The exposure led to formation of α‐Syn inclusions and oligomers of 34, 54, 68 kDa and higher molecular weights. The oligomers displayed immunoreactivity with antibodies to the amino‐, but not to the carboxyl(C)‐, terminus of α‐Syn, indicating that C‐terminally truncated α‐Syn is a major component of oligomers. FeCl2 exposure also promoted accumulation of S129 phosphorylated monomeric α‐Syn (Pα‐Syn) and casein kinase 2 (CK2); however, G‐protein‐coupled receptor kinase 2 was reduced. Treatment of FeCl2‐exposed cells with CK2 inhibitors (DRB or TBB) led to decreased formation of α‐Syn inclusions, oligomers and Pα‐Syn. FeCl2 exposure also enhanced the activity/level of cathepsin D. Treatment of the FeCl2‐exposed cells with pepstatin A or NH4Cl led to reduced formation of oligomers/inclusions as well as of ∼ 10 and 12 kDa truncated α‐Syn. Our results indicate that α‐Syn phosphorylation caused by FeCl2 is due to CK2 upregulation, and that lysosomal proteases may have a role in producing truncated α‐Syn for oligomer assembly.
Function and accuracy of glucose sensors beyond their stated expiry date.

BACKGROUND The sensor of the Continuous Glucose Monitoring System (CGMS, Medtronic Minimed, Northridge, CA) is labeled to expire 6 months following its production and to measure the glucose concentration in interstitial fluid up to 3 days after insertion. The purpose of this study was to demonstrate potential possibilities of sensors when used beyond their expiry date. METHODS Twenty sensors, each between 3 to 18 months after the expiry date, were assessed in a 7-day period after insertion. Twenty healthy volunteers 23.4 +/- 2.92 (mean +/- SD) years old were trained in handling the CGMS and the Hypoguard (Woodbridge, UK) Advance glucometer system to measure their capillary plasma glucose concentration 18 times a day. Sensor function was estimated according to the number of readings per day, the accuracy according to the mean absolute difference (MAD), and correlation coefficient (r) between glucometer and sensor resulting from paired values. RESULTS Uninterrupted sensor function was found in 117 of 140 sensor-days (83.6%). A reduction of readings in 23 sensor-days (16.4%) was caused by user error (5 sensor-days, 3.6%), connecting cable (7 sensor-days, 5%), sensor failure (8 sensor-days, 5.7%), or uncertain factors (3 sensor-days, 2.1%). MAD was always < 28%, and r = 0.79. CONCLUSIONS Neither the expiry date nor the 3-day period of use limits the reliable function of a CGMS sensor. Sensors were found to function as long as 18 months after the expiry date, mostly for at least 7 days. There were no serious local adverse reactions. Prolongation of shelflife label and insertion time appears to be reasonable. Further studies are in progress.
Implementation and application of a versatile clustering tool for tandem mass spectrometry data

High‐throughput proteomics experiments typically generate large amounts of peptide fragmentation mass spectra during a single experiment. There is often a substantial amount of redundant fragmentation of the same precursors among these spectra, which is usually considered a nuisance. We here discuss the potential of clustering and merging redundant spectra to turn this redundancy into a useful property of the dataset. To this end, we have created the first general‐purpose, freely available open‐source software application for clustering and merging MS/MS spectra. The application also introduces a novel approach to calculating the similarity of fragmentation mass spectra that takes into account the increased precision of modern mass spectrometers, and we suggest a simple but effective improvement to single‐linkage clustering. The application and the novel algorithms are applied to several real‐life proteomic datasets and the results are discussed. An analysis of the influence of the different algorithms available and their parameters is given, as well as a number of important applications of the overall approach.
CD4 Down-regulation by HIV-1 and Simian Immunodeficiency Virus (SIV) Nef Proteins Involves Both Internalization and Intracellular Retention Mechanisms*

Among the pleiotropic effects of Nef proteins of HIV and simian immunodeficiency virus (SIV), down-modulation of cell surface expression of CD4 is a prominent phenotype. It has been presumed that Nef proteins accelerate endocytosis of CD4 by linking the receptor to the AP-2 clathrin adaptor. However, the related AP-1 and AP-3 adaptors have also been shown to interact with Nef, hinting at role(s) for these complexes in the intracellular retention of CD4. By using genetic inhibitors of endocytosis and small interfering RNA-induced knockdown of AP-2, we show that accelerated CD4 endocytosis is not a dominant mechanism of HIV-1 (NL4-3 strain) Nef in epithelial cells, T lymphocyte cell lines, or peripheral blood lymphocytes. Furthermore, we show that both the CD4 recycling from the plasma membrane and the nascent CD4 in transit to the plasma membrane are susceptible to intracellular retention in HIV-1 Nef-expressing cells. In contrast, AP-2-mediated enhanced endocytosis constitutes the predominant mechanism for SIV (MAC-239 strain) Nef-induced down-regulation of human CD4 in human cells.
Rate of cervical cancer, severe intraepithelial neoplasia, and adenocarcinoma in situ in primary HPV DNA screening with cytology triage: randomised study within organised screening programme

Objective To assess the performance and impact of primary human papillomavirus (HPV) DNA screening with cytology triage compared with conventional cytology on cervical cancer and severe pre-cancerous lesions. Design Randomised trial. Setting Population based screening programme for cervical cancer in southern Finland in 2003-5. Participants 58 076 women, aged 30-60, invited to the routine population based screening programme for cervical cancer. Interventions Primary HPV DNA test (hybrid capture II) with cytology triage if the result was positive or conventional cytological screening (reference). Main outcome measures Rate of cervical cancer, cervical intraepithelial neoplasia (CIN) grade III, and adenocarcinoma in situ (as a composite outcome referred to as CIN III+) during 2003-7 through record linkage between files from the screening registry and the national cancer registry. Results In the HPV and conventional arms there were 95 600 and 95 700 woman years of follow-up and 76 and 53 cases of CIN III+, respectively (of which six and eight were cervical cancers). The relative rate of CIN III+ in the HPV arm versus the conventional arm was 1.44 (95% confidence interval 1.01 to 2.05) among all women invited for screening and 1.77 (1.16 to 2.74) among those who attended. Among women with a normal or negative test result, the relative rate of subsequent CIN III+ was 0.28 (0.04 to 1.17). The rate of cervical cancer between arms was 0.75 (0.25 to 2.16) among women invited for screening and 1.98 (0.52 to 9.38) among those who attended. Conclusions When incorporated into a well established organised screening programme, primary HPV screening with cytology triage was more sensitive than conventional cytology in detecting CIN III+ lesions. The number of cases of cervical cancer was small, but considering the high probability of progression of CIN III the findings are of importance regarding cancer prevention. Trial registration Current Controlled Trials ISRCTN23885553.
Cell segmentation and tracking using CNN-based distance predictions and a graph-based matching strategy

The accurate segmentation and tracking of cells in microscopy image sequences is an important task in biomedical research, e.g., for studying the development of tissues, organs or entire organisms. However, the segmentation of touching cells in images with a low signal-to-noise-ratio is still a challenging problem. In this paper, we present a method for the segmentation of touching cells in microscopy images. By using a novel representation of cell borders, inspired by distance maps, our method is capable to utilize not only touching cells but also close cells in the training process. Furthermore, this representation is notably robust to annotation errors and shows promising results for the segmentation of microscopy images containing in the training data underrepresented or not included cell types. For the prediction of the proposed neighbor distances, an adapted U-Net convolutional neural network (CNN) with two decoder paths is used. In addition, we adapt a graph-based cell tracking algorithm to evaluate our proposed method on the task of cell tracking. The adapted tracking algorithm includes a movement estimation in the cost function to re-link tracks with missing segmentation masks over a short sequence of frames. Our combined tracking by detection method has proven its potential in the IEEE ISBI 2020 Cell Tracking Challenge (http://celltrackingchallenge.net/) where we achieved as team KIT-Sch-GE multiple top three rankings including two top performances using a single segmentation model for the diverse data sets.
Thromboembolic complications in the nephrotic syndrome.

A 67-year-old woman presented with progressive dyspnea and both legs swelling for recent 2 months. She denied any known history of systemic illness. Physical examination shows clear lungs, normal heart sounds without murmurs and pitting edema of his lower extremities bilaterally. The laboratory investigation data were as follows: leukocyte 6110 cells/μl; …
The effects of aging on speech perception in noise: comparison between normal-hearing and cochlear-implant listeners.

BACKGROUND Speech understanding in noise is comparatively more problematic for older listeners with and without hearing loss, and age-related changes in temporal resolution might be associated with reduced speech recognition in complex noise. PURPOSE The purpose of this study was to investigate the effects of aging on temporal processing and speech perception in noise for normal-hearing (NH) and cochlear-implant (CI) listeners. RESEARCH DESIGN All participants completed three experimental procedures: (1) amplitude modulation (AM) detection thresholds, (2) sentence recognition in quiet, and (3) speech recognition in steady or modulating noise. STUDY SAMPLE Four listener groups participated in the study: 11 younger (≤ 30 yr old, YNH) listeners and 12 older (> 60 yr old, ONH) listeners with NH and 7 younger (< 55 yr old, YCI) and 6 older (> 60 yr old, OCI) CI users. CI listeners have been wearing their device either monaurally or binaurally at least 1 yr. DATA COLLECTION AND ANALYSIS For speech recognition testing, there were eight listening conditions in noise (4 modulation frequencies × 2 signal-to-noise ratios) and one in quiet for each listener. For modulation detection testing, a broadband noise with a duration of 500 msec served as the stimuli at three temporal modulation frequencies of 2, 4, and 8 Hz, which were used to modulate the noise in the speech recognition experiment. We measured AM detection thresholds using a two-interval, two-alternative, forced-choice adaptive procedure. We conducted a series of analysis of variance tests to examine the effect of aging on each test result and measured the correlation coefficient between speech recognition in noise and modulation detection thresholds. RESULTS Although older NH and CI listeners performed similar to the younger listeners with the same hearing status for sentence recognition in quiet, there was a significant aging effect on speech recognition in noise. Regardless of modulation frequency and signal-to-noise ratio, speech recognition scores of the older listeners were poorer than those of the younger listeners when hearing status was matched. We also found a significant effect of aging on AM detection at each modulating frequency and a strong correlation between speech recognition in modulating noise and AM detection thresholds at 2 and 4 Hz. CONCLUSIONS Regardless of differences in hearing status, the degree and pattern of aging effect on auditory processing of the NH listener groups were similar to those of the CI listener groups. This result suggests that age-related declines in speech understanding are likely multifactorial, including peripheral and central factors. Although the age cutoff of the current older age group was 10 yr less than in previous studies (Dubno et al, 2002; Lin et al, 2011), we still found the age-related differences on two auditory tasks. This study extends the knowledge of age-related auditory perception difficulties to CI listeners.
Second Messenger Pas de Deux: The Coordinated Dance Between Calcium and cAMP

Dynamic calcium signaling is a well-established precept in biology. Different cell types exhibit spontaneous as well as stimulus-triggered transient changes in the concentration of intracellular calcium. Does this behavior extend to other second messengers? Optical dissection of various signal transduction pathways with fluorescent reporter molecules that enable visualization of changes in concentration of other second messengers is well under way. Recent research using technologically refined probes provides improved temporal and spatial resolution of adenosine 3′,5′-monophosphate (cAMP) dynamics to generate insights into the bidirectional interplay between intracellular fluctuations of cAMP and calcium. cAMP oscillations are generated in response to hormones, and cells can recognize and differentially respond to transient versus sustained changes in this second messenger. Second messenger reporters are now available to track multiple players and so provide a dynamic picture of signaling networks.
Erratum: Diet Quality Predicts Visceral Adiposity and Liver Fatness: The Multiethnic Cohort Study

After publication of this article, the authors detected a labeling error for one of the four dietary index variables in the data set. The Healthy Eating Index (HEI) 2010 variable for cohort entry was actually the HEI 2005 for the dietary data collected at cohort entry. However, it was correctly labeled for the diet data collected at the clinic visit. (The HEI 2005 was developed based on the dietary recommendations made to the US population in 2005, whereas the 2010 HEI was developed based on the 2010 recommendations. These recommendations have not changed dramatically between these two dates.) Therefore, all the results in the tables, figures, and text of the manuscript referring to diet quality at cohort entry show associations for the HEI 2005 and not for the HEI 2010 as stated in the manuscript. The results for the other three diet quality indices were not affected.
Local Change in Phospholipid Composition at the Cleavage Furrow Is Essential for Completion of Cytokinesis*

Cell division ends up with the membrane separation of two daughter cells, presumably by a membrane fusion that requires dynamic changes of the distribution and the composition of membrane lipids. We have previously shown that a membrane lipid phosphatidylethanolamine (PE) is exposed on the cell surface of the cleavage furrow during late cytokinesis and that this PE movement is involved in regulation of the contractile ring disassembly. Here we show that immobilization of cell surface PE by a PE-binding peptide blocks the RhoA inactivation in the late stage of cytokinesis. Phosphatidylinositol 4-phosphate 5-kinase (PIP5K), but not other RhoA effectors, is co-localized with RhoA in the peptide-treated cells. Indeed, PIP5K and its product phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) are localized to the cleavage furrow of normally dividing cells. Both overexpression of a kinase-deficient PIP5K mutant and microinjection of anti-PI(4,5)P2 antibodies compromise cytokinesis by preventing local accumulation of PI(4,5)P2 in the cleavage furrow. These findings demonstrate that the localized production of PI(4,5)P2 is required for the proper completion of cytokinesis and that the possible formation of a unique lipid domain in the cleavage furrow membrane may play a crucial role in coordinating the contractile rearrangement with the membrane remodeling during late cytokinesis.
Uses of Next-Generation Sequencing Technologies for the Diagnosis of Primary Immunodeficiencies

Primary immunodeficiencies (PIDs) are genetic disorders impairing host immunity, leading to life-threatening infections, autoimmunity, and/or malignancies. Genomic technologies have been critical for expediting the discovery of novel genetic defects underlying PIDs, expanding our knowledge of the complex clinical phenotypes associated with PIDs, and in shifting paradigms of PID pathogenesis. Once considered Mendelian, monogenic, and completely penetrant disorders, genomic studies have redefined PIDs as a heterogeneous group of diseases found in the global population that may arise through multigenic defects, non-germline transmission, and with variable penetrance. This review examines the uses of next-generation DNA sequencing (NGS) in the diagnosis of PIDs. While whole genome sequencing identifies variants throughout the genome, whole exome sequencing sequences only the protein-coding regions within a genome, and targeted gene panels sequence only a specific cohort of genes. The advantages and limitations of each sequencing approach are compared. The complexities of variant interpretation and variant validation remain the major challenge in wide-spread implementation of these technologies. Lastly, the roles of NGS in newborn screening and precision therapeutics for individuals with PID are also addressed.
HLA‐A, HLA‐B, HLA‐DRB1 allele and haplotype frequencies of 14 529 Chinese Han bone marrow donors living in Dalian, China

We investigated the allele and haplotype frequencies of HLA‐A, HLA‐B and HLA‐DRB1 loci in Dalian Chinese Han population using blood samples of unrelated marrow donors who live in Dalian. The genetic relationship between Dalian and different regions worldwide was further explored based on HLA status of different populations. A total of 14 529 samples were genotyped at 2‐digit level only by sequence‐specific oligonucleotide and sequence‐based typing methods. Allele frequencies of HLA‐A, HLA‐B and HLA‐DRB1 were calculated by the direct counting method. Haplotype frequencies and linkage disequilibrium (LD) values were calculated by the maximum likelihood method. FST values were calculated by allele frequency data of each locus. Phylogeny tree of Nei's DA genetic distances was constructed by the UPGMA method. HLA‐A*02 was the most frequent allele at HLA‐A locus followed by A*11 and A*24. Alleles at HLA‐B locus ranked in decreasing order by frequency were B*40, B*15 and B*13. The three highest frequency alleles were DRB1*15, DRB1*09 and DRB1*12 at HLA‐DRB1 locus. A*30‐B*13‐DRB1*07 was the most frequent three‐locus haplotype. For the population relationships, Dalian had a relative close genetic relationship with Liaoning and Yantai‐Weihai and a relative distant genetic relationship with Australia. The information obtained in this study may provide useful information for anthropological studies, for disease‐association studies and helping bone marrow transplantation patients to search HLA‐matched donors.
Impact of bistrand abasic sites and proximate orientation on DNA global structure and duplex energetics

Bistrand lesions embedded within a single helical turn of tridecameric deoxyoligonucleotide duplexes represent a model system for exploring the impact of clustered lesions that occur in vivo and pose a significant challenge to cellular repair machineries. Such investigations are essential for understanding the forces that dictate lesion‐induced mutagenesis, carcinogenesis, and cytotoxicity within a context that mimics local helical perturbations caused by an ionizing radiation event. This study characterizes the structural and energy profiles of DNA duplexes harboring synthetic abasic sites (tetrahydrofuran, F) as models of clustered bistrand abasic (AP) lesions. The standard tridecameric dGCGTACCCATGCG·dCGCATGGGTACGC duplex is employed to investigate the energetic impact of single and bistrand AP sites by strategically replacing one or two bases within the central CCC/GGG triplet. Our combined analysis of temperature‐dependent UV and circular dichroism (CD) profiles reveals that the proximity and relative orientation of AP sites within bistrand‐damaged duplexes imparts a significant thermodynamic impact. Specifically, 3′‐staggered lesions (CCF/GFG) exert a greater destabilizing effect when compared with their 5′‐counterpart (FCC/GFG). Moreover, a duplex harboring the central bistrand AP lesion (CFC/GFG) is moderately destabilized yet exhibits distinct properties relative to both the 3′ and 5′‐orientations. Collectively, our energetic data are consistent with structural studies on bistrand AP‐duplexes of similar sequence in which a 3′‐staggered lesion exerts the greatest perturbation, a finding that provides significant insight regarding the impact of orientation on lesion repair processing efficiency.
Simultaneous control of the compass-gait biped to maintain symmetric gait across all mass ratios

It is known that the hybrid dynamical model of a compass-gait biped, which is used here to represent a patient using ankle-foot prostheses on both legs, exhibits a loss of stable period-one symmetric gait with increasing hip-to-leg mass ratio. For higher mass ratios, the period-one gait becomes unstable and bifurcates into a period-two asymmetric gait. In this work, the continuous-time single-support phase of the compass-gait biped is linearized about the upright position and simultaneously stabilized by a linear time-invariant controller that is simple, single-input single-output, and only second-order. This controller, when simulated with the underactuated nonlinear hybrid compass-gait biped model, is shown to maintain stable period-one symmetric gait across all physiologically meaningful mass distributions of the compass-gait biped.