Miracle-dz/UniFAR-FTUs huggingface dataset:
Lysosomal degradation of endocytosed proteins depends on the chloride transport protein ClC‐7

Mutations in either ClC‐7, a late endoso‐ mal/lysosomal member of the CLC family of chloride channels and transporters, or in its β‐subunit Ostm1 cause osteopetrosis and lysosomal storage disease in mice and humans. The severe phenotype of mice globally deleted for ClC‐7 or Ostm1 and the absence of storage material in cultured cells hampered investiga‐ tions of the mechanism leading to lysosomal pathology in the absence of functional ClC‐7/Ostm1 transporters. Tissue‐specific ClC‐7‐knockout mice now reveal that accumulation of storage material occurs cell‐autono‐ mously in neurons or renal proximal tubular cells lacking ClC‐7. Almost all ClC‐7‐deficient neurons die. The activation of glia is restricted to brain regions where ClC‐7 has been inactivated. The effect of ClC‐7 disruption on lysosomal function was investigated in renal proximal tubular cells, which display high endo‐ cytotic activity. Pulse‐chase endocytosis experiments in vivo with mice carrying chimeric deletion of ClC‐7 in proximal tubules allowed a direct comparison of the handling of endocytosed protein between cells express‐ ing or lacking ClC‐7. Whereas protein was endocytosed similarly in cells of either genotype, its half‐life in‐ creased significantly in ClC‐7‐deficient cells. These ex‐ periments demonstrate that lysosomal pathology is a cell‐autonomous consequence of ClC‐7 disruption and that ClC‐7 is important for lysosomal protein degrada‐ tion. —Wartosch, L. , Fuhrmann, J. C. , Schweizer, M. , Stauber, T. , Jentsch, T. J. Lysosomal degradation of endocytosed proteins depends on the chloride trans‐ port protein ClC‐7. FASEB J. 23, 4056 – 4068 (2009). www.fasebj. org
Potentially inappropriate prescriptions in patients admitted to a psychiatric hospital

Abstract Background Very little is known about the general appropriateness of prescribing for psychiatric patients. Aims To identify prevalence and types of potentially inappropriate prescribing (PIP) of psychotropic and somatic medications, to assess the severity of potential clinical consequences and to identify possible predictive factors of PIP in a sample of adult psychiatric in-patients. Methods A descriptive, cross-sectional design using medication reviews by clinical pharmacologists to identify PIP during a 3-month period. The setting was in-patient units in a psychiatric department of a Danish university hospital during a 3-month period (September 2013–November 2013). Patients medication lists (n = 207) were reviewed at the time of admission and all identified PIPs were assessed for potential consequences by clinical pharmacologists. Results There were 349 PIP identified in 1291 prescriptions. The proportion of patients found to have at least one PIP was 123/207 (59%) and the proportions of patients with at least one PIP assessed to be potentially serious or fatal was 69/207 (33%) and 24/207 (12%), respectively. Interactions between drugs 125/207 (36%) and too high doses of drugs 56/207 (16%) were the most frequent PIP. Predictive factors for PIP were polypharmacy (>5 prescriptions) and having one or more somatic diagnoses. Conclusion PIP is common in psychiatric patients and potentially fatal. Particularly polypharmacy (>5 prescriptions) and concomitant somatic illness were associated with the probability of PIP. Improving the quality of prescribing might benefit from an interprofessional approach and thus better training of physicians and nurses is needed in order to minimize PIP.
Center bias enhanced visual saliency detection method

Due to the advancement in multimedia technology, the images and videos play a major role in day today life. How the humans are looking into the image? The computational models of visual attention used in many of the computer vision tasks such as image segmentation, object recognition, image understanding, etc. The proposed method aims to construct visual saliency model with the help of the center bias and pre-attentive features. The bottom-up visual saliency model is introduced. Influence of Center bias is the key mechanism of the proposed method. Difference of Gaussian (DOG) filter and gaussian envelope function are used to identify the salient objects of an image. The experimental results of the proposed method compared with five state-of-art-methods. The benchmark database is used to obtain the performance metrics. Receiver Operating Characteristics (ROC), precision, recall and f-measure are found to analyze the performance of the proposed method.
Providing online support for young people with mental health difficulties: challenges and opportunities explored

Despite its growing popularity there is a paucity of information exploring the potential of the Internet to build a trusted community that helps reduce stigma, facilitates help‐seeking and aids in the prevention or helps in the management of mental health difficulties for young people. Unsupervised online forums or chat rooms hold potential dangers for young people including the possibility of attracting adults who may take advantage of vulnerable adolescents. Contagion with members organizing suicide pacts, or describing suicidal or self‐harming intentions and methods and young people ruminating about feeling depressed are also potential risks. This paper describes the development and conceptual underpinnings of the Reach Out! Online Community Forum, a moderated bulletin board, developed in consultation with, and facilitated by young people aged 16–25. The Forum, although facilitated by young people, is supported and monitored by trained moderators. Anecdotal evidence collected via unsolicited feedback from young people using the Forum suggests that it is a positive, unique and helpful online experience although little is known about the impact on stigma reduction and help seeking in the offline world. Given the proliferation of unsupervised forums and chat rooms there is a need for further research to determine the effectiveness or potential dangers of online forums in mental health prevention and early intervention work.
The prognostic value of radiologic parameters for long-term outcome assessment after an isolated unilateral calcaneus fracture.

OBJECTIVE The current retrospective case-control study examines the prognostic value of radiologic parameters for long-term clinical outcome assessment after a calcaneus fracture. METHODS In the authors' trauma department 262 adult patients with an isolated calcaneus fracture were treated from 1995 to 2005. Using conventional x-ray and computed tomography imaging. the calcaneal fractures were classified according to Sanders system. In addition, Boehler's and Gissane's angles were measured before and after therapy and the Larsen stage of subtalar arthrosis was determined. After a mean follow-up interval of 9.5 years, 44 patients were available for clinical and radiological assessment. RESULTS At the time of trauma the average age of the study group was 52 (range, 29-79) years. Thirty-seven patients were treated operatively and seven conservatively. Patients with a negative Boehler's angle, upon admission, exhibited significantly worse results using four of the five clinical scoring systems than patients with a preserved or slight reduced Boehler's angle. Operative treatment in patients whose Boehler's angle was elevated to normal range or beyond exhibited %worse better results than patients with an over-correction of Boehler's angle. In 11 cases, two primary and nine secondary subtalar arthrodeses were performed. The degree of subtalar arthrosis as per Larsen was increased 2.54 ± 1.14 in the course of hospital admission, arthrodesis and/or follow up examination. The results show no significant difference between operative and conservative treatment. CONCLUSIONS Boehler's angle at time of admission appears to be a valuable prognosticator for functional long-term results after calcaneus fracture. An operative over-correction of a reduced Boehler's angle should be avoided.
A silent event‐related functional MRI technique for brain activation studies without interference of scanner acoustic noise

A new data acquisition method for silent, event‐related functional MRI in which scanner acoustic noise does not interfere with brain activation is introduced and evaluated in an auditory tonotopic mapping experiment. This method takes into account the hemodynamic‐response characteristics of the brain during activation, associated with both task performance and scanner noise. A data acquisition scheme was designed to collect task‐induced brain activation signals without interference of scanner noise on stimulus delivery or on the measured response. The advantages of the technique were demonstrated in a tonotopic mapping experiment of human auditory cortex. Tonotopic maps obtained by the technique in normal subjects showed distinct spatial shifts of the activation foci in the lateral part of Heschl's gyrus with changing stimulus frequency, whereas no systematic shift was shown in a conventional event‐related experiment using the same stimulation paradigm. Signal change in the activation foci with the new technique was 54% larger than with the conventional technique, suggesting an increased dynamic range of the signal change associated with task‐induced brain activation under silent conditions. Magn Reson Med 43:185–190, 2000. © 2000 Wiley‐Liss, Inc.
Assignment of Staphylococcus Isolates to Groups by spa Typing, SmaI Macrorestriction Analysis, and Multilocus Sequence Typing

ABSTRACT The implementation of the new clustering algorithm Based Upon Repeat Pattern (BURP) into the Ridom StaphType software tool enables clustering based on spa typing data for Staphylococcus aureus. We compared clustering results obtained by spa typing/BURP to those obtained by currently well-established methods, i.e., SmaI macrorestriction analysis and multilocus sequence typing/eBURST. A total of 99 clinical S. aureus strains, including MRSA and representing major clonal lineages associated with important kinds of infections which have been prevalent in Germany and Central Europe during the last 10 years, were used for comparison. SmaI macrorestriction analysis revealed the highest discriminatory power, and clustering results for all three methods resulted in concordance values ranging from 96.8% between the two sequence-based methods to 93.4% between spa typing/BURP and SmaI macrorestriction/cluster analysis. The results of this study indicate that spa typing, together with BURP clustering, is a useful tool in S. aureus epidemiology, especially because of ease of use and the advantages of unambiguous sequence analysis as well as reproducibility and exchange of typing data.
The Biochemical and Phenotypic Characterization of Hho1p, the Putative Linker Histone H1 of Saccharomyces cerevisiae *

There is currently no published report on the isolation and definitive identification of histone H1 inSaccharomyces cerevisiae. It was, however, recently shown that the yeast HHO1 gene codes for a predicted protein homologous to H1 of higher eukaryotes (Landsman, D. (1996) Trends Biochem. Sci. 21, 287–288; Ushinsky, S. C. , Bussey, H. , Ahmed, A. A. , Wang, Y. , Friesen, J., Williams, B. A. , and Storms, R. K. (1997) Yeast 13, 151–161), although there is no biochemical evidence that shows that Hho1p is, indeed, yeast histone H1. We showed that purified recombinant Hho1p (rHho1p) has electrophoretic and chromatographic properties similar to linker histones. The protein forms a stable ternary complex with a reconstituted core di-nucleosome in vitro at molar rHho1p:core ratios up to 1. Reconstitution of rHho1p with H1-stripped chromatin confers a kinetic pause at ∼168 base pairs in the micrococcal nuclease digestion pattern of the chromatin. These results strongly suggest that Hho1p is a bona fide linker histone. We deleted the HHO1 gene and showed that the strain is viable and has no growth or mating defects. Hho1p is not required for telomeric silencing, basal transcriptional repression, or efficient sporulation. Unlike core histone mutations, a hho1Δ strain does not exhibit a Sin or Spt phenotype. The absence of Hho1p does not lead to a change in the nucleosome repeat length of bulk chromatin nor to differences in the in vivo micrococcal nuclease cleavage sites in individual genes as detected by primer extension mapping.
Quantification of free water transport in peritoneal dialysis.

BACKGROUND In peritoneal dialysis (PD) total net ultrafiltration (NUF) is dependent on transport through small pores and through water channels in the peritoneum. These channels are impermeable to solutes, and therefore, crystalloid osmotic-induced free water transport occurs through them. Several indirect methods to assess free water transport have been suggested. The difference in NUF between a 3.86% and a 1.36% solution gives a rough indication, but is very time consuming. The magnitude of the dip in dialysate/plasma (D/P) sodium in the initial phase of a 3.86% exchange is another way to estimate free water transport. In the present study, a method was applied to calculate free water transport by calculating sodium-associated water transport in one single 3.86% glucose dwell. METHODS Forty PD patients underwent one standard peritoneal permeability analysis (SPA) with a 1.36% glucose solution, and another with a 3.86% glucose solution. At different time points intraperitoneal volume and sodium concentration were assessed. This made it possible to calculate total sodium transport. By subtracting this transport (which must have occurred through the small pores) from the total fluid transport, free water transport remained. These results were compared with the other methods to estimate free water transport. RESULTS For the 1.36% glucose dwell, total transcapillary ultrafiltration in the first hour (TCUF(0-60)) was 164 mL, transport through the small pores was 129 mL, and free water transport was 35 mL (21%). For the 3.86% glucose solution, total TCUF(0-60) was 404 mL, transport through the small pores was 269 mL, and free water transport was 135 mL (34%). The contribution of free water transport in the first minute (TCUF(0-1)) was 39% of the total fluid transport. From the 40 patients, 11 patients had ultrafiltration failure (NUF <400 mL after 4 hours). For these patients the contribution of free water to TCUF(0-1) was significantly lower than for those with normal ultrafiltration (20% vs. 48%, P < 0.05). A strong correlation was present between free water transport as a percentage of total fluid transport and the maximum dip in D/P sodium (r= 0.84). The correlation was not significant with the difference in net ultrafiltration of 3.86% and 1.36% solutions (r= 0.24, P= 0.3). CONCLUSION The method applied here is the first direct quantification of free water transport, calculated from a single standard peritoneal function test. It offers a quick possibility to evaluate patients suffering from ultrafiltration failure. In these patients free water transport was impaired, but the origin of this impairment is still to be determined.
Development and cytolytic function of intestinal intraepithelial T lymphocytes in antigen‐minimized mice

Intraepithelial T lymphocytes in the small intestine (IEL) consist of αβ T‐cell receptor (TCR)‐bearing T cells (αβ‐IEL) and γδ TCR‐bearing T cells (γδ‐IEL). Development and cytolytic activation of αβ‐IEL sharply attenuate in germ‐free (GF) mice fed a natural diet (Nat‐GF), but the number and cytotoxicity of γδ‐IEL are comparable between conventional (CV) and Nat‐GF mice. In this report, we compared the properties of IEL in Nat‐GF mice and GF mice fed antigen‐minimized diet (AgM‐GF mice) of C57BL/6 strain to evaluate an influence of gut antigenic load on IEL development. Numbers of αβ‐IEL and γδ‐IEL in AgM‐GF mice were less by 1.9‐ and 1.4‐fold than those in Nat‐GF mice, respectively. Significant decreases in the proportions of CD4+8−, CD4−8αβ+, and CD4+8+ subsets and a resultant increase in the ratio of CD4−8αα+ subset were evident in αβ‐IEL of Nat‐GF mice compared with CV mice, but the subset constitution of αβ‐IEL was similar between Nat‐GF and AgM‐GF mice. In contrast, relative composition of γδ‐IEL was not different between CV, Nat‐GF, and AgM‐GF mice. αβ‐IEL displayed low cytolytic activity in Nat‐GF mice and were almost deprived of their cytotoxicity under the antigen‐minimized condition. While γδ‐IEL were strongly cytolytic in Nat‐GF mice their cytolytic activity was remarkably reduced in AgM‐GF mice. These results indicate that γδ‐IEL are activated independently of microbial colonization in the gastrointestinal tract but their activation occurs in response to the exogenous antigenic substances other than live micro‐organisms.
Differential Diagnosis of Psychotic Symptoms : Medical “ Mimics ”

Karl Bonhoeffer, 19091 The number of medical diseases that can present with psychotic symptoms (ie, delusions, hallucinations) is legion. A thorough differential diagnosis of possible medical and toxic causes of psychosis is necessary to avoid the mistaken attribution of psychosis to a psychiatric disorder. One organizing principle separates etiology into primary psychiatric and secondary categories, the latter includes delirium (toxic psychosis), dementia, medical illnesses, and substances (Figure) This terminology avoids the term “organic,” which implies a mind-body dichotomy that is no longer tenable.2 Psychosis can be attributable to a combination of factors, and all possible causes must be systematically examined, hence the lack of a hierarchical organization in this nosology.In this article, I focus on secondary psychosis due to a medical illness or substances and not on the cognitive disorders of delirium and dementia. It is important, however, to be aware that both are commonly associated with psychosis. Psychosis is a frequent ancillary symptom of delirium that can overshadow its cardinal cognitive features.3,4 It is therefore critical to routinely consider the possibility of a delirium in any patient with psychosis. Dementias are also frequently accompanied by neuropsychiatric problems, including psychosis.5 Psychosis is present in about 40% of patients with Alzheimer disease, the most common form of dementia.6 Most patients with Lewy body dementia experience psychosis as well. Hallucinations, usually visual, are the most frequent psychotic symptom; they occur in 78% of patients, followed by misidentifications in 56% and delusions in 25%. 7,8
Intra- and inter-rater reliability of the selective functional movement assessment (sfma).

PURPOSE/BACKGROUND The Selective Functional Movement Assessment (SFMA) is a clinical assessment system designed to identify musculoskeletal dysfunction by evaluation of fundamental movements for limitations or symptom provocation. The purpose of this study was to determine the intra- and inter-rater reliability of the ten fundamental movement patterns of the SFMA in a healthy population using the SFMA categorical and criterion checklist scoring tools. METHODS 35 healthy subjects (22.9 years +/- 1.9) were recorded with two digital video cameras (1-frontal view/1-sagittal view) while they performed the ten fundamental movements patterns that comprise the SFMA. Evaluators with varying experience with the SFMA (rater A, > 100 hours; rater B, 25 hours; and rater C, 16 hours) and not present at the initial data collection evaluated each video using categorical and criterion checklist scoring tools. Evaluators repeated this process at least one week later. The evaluators' composite results were compared between and within raters using the kappa coefficient and ICC's for categorical scoring and criterion checklist scoring, respectively. RESULTS Substantial to almost perfect intra-rater reliability of the SFMA (kappa, % agreement) was observed for all raters using the categorical scoring tool (rater A: .83, .91; rater B: .78, .88; and rater C: .72, .85). The criterion checklist scoring tool yielded intra-rater ICCs (3,1; 95% confidence interval) ranging from good to poor with rater A demonstrating the highest reliability (ICC [SEM]) (.52 [2.36]) and rater C the lowest reliability (.26 [3.42]). Inter-rater reliability of the categorical scoring tool was slight to substantial (.41-.61, .69-.79) while the criterion checklist tool (ICC 2,1) demonstrated unacceptable inter-rater reliability when assessed in all raters together (.43 [2.7]). CONCLUSIONS As hypothesized, intra-and inter-rater reliability of categorical scoring and criterion checklist scoring of the ten fundamental movements of the SFMA was higher in raters with greater experience.
High Variation in Resource Allocation Strategies among 11 Indian Wheat (Triticum aestivum) Cultivars Growing in High Ozone Environment

Eleven local cultivars of wheat (Triticum aestivum) were chosen to study the effect of ambient ozone (O3) concentration in the Indo-Gangetic Plains (IGP) of India at two high-ozone experimental sites by using 300 ppm of Ethylenediurea (EDU) as a chemical protectant against O3. The O3 level was more than double the critical threshold reported for wheat grain production (AOT40 8.66 ppm h). EDU-grown plants had higher grain yield, biomass, stomatal conductance and photosynthesis, less lipid peroxidation, changes in superoxide dismutase and catalase activities, changes in content of oxidized and reduced glutathione compared to non-EDU plants, thus indicating the severity of O3 induced productivity loss. Based on the yield at two different growing sites, the cultivars could be addressed in four response groups: (a) generally well-adapted cultivars (above-average yield); (b) poorly-adapted (below-average yield); (c) adapted to low-yield environment (below-average yield); and (d) sensitive cultivars (adapted to high-yield environment). EDU responses were dependent on the cultivar, the developmental phase (vegetative, flowering and harvest) and the experimental site.
Cancer risks in hairdressers: Assessment of carcinogenicity of hair dyes and gels

More than a decade ago, an increased risk for bladder cancer among male hairdressers was established. Frequent changes of hair dye formulations together with their widespread use call for safety guarantees. We carried out a follow‐up study of a cohort of 38,866 female and 6,824 male hairdressers from Sweden and analyzed all of their malignancies over a period of 39 years. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for 28 cancer sites were calculated using the economically active population as a reference. During the years 1960–1998 a total of 1,043 cancer cases were recorded in male hairdressers. Excess risks for cancers of the upper aerodigestive tract and lung and colorectal adenocarcinoma were observed. Additionally, male hairdressers working in 1960 had an increased risk for urinary bladder cancer, which was highest in the 1960s with an SIR of 2.56 (95% CI 1.36–4.39) and decreased with the follow‐up time. A total of 2,858 cancers were recorded in female hairdressers. An increased risk was observed for cancers of the pancreas, lung and cervix and in situ cancer of the skin. The increased risk for in situ skin cancer specifically affected the scalp and neck, sites of contact for hair dyes, with an SIR of 2.43 (95% CI 1.14–4.44). The increase in lung cancer, the only site for which cancer was increased in either sex, may depend on confounding from smoking. Bladder cancer was not increased among hairdressers in the recent decades and is therefore not likely to be associated with modern hair dyes. © 2003 Wiley‐Liss, Inc.
Achieving durable glucose control in the intensive care unit without hypoglycaemia : a new practical IV insulin protocol

Hyperglycaemia occurs in a substantial portion of critically ill patients in our intensive care units. Near normalization of elevated blood glucose levels with IV insulin may improve outcome. However, currently published IV insulin protocol are not ideal; most are relatively complex and often result in hypoglycaemia. We designed a protocol that would be practical to use while incorporating the necessary complexities required to achieve good glucose control, coupled with a low incidence hypoglycaemia.