Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Serum Cystatin C and Creatinine Levels among Individuals with Persisting Proteinuria in Farming Communities of Rural Sri Lanka

Background Chronic kidney disease of uncertain aetiology (CKDu) is one of the major health concerns among agricultural communities in Sri Lanka. Individuals involved in severe agricultural works for their livelihood are highly vulnerable for this disease and patients have been detected with persisting proteinuria at community-level screening. The current study was designed to evaluate the diagnosis of two functional markers of kidney damage using individuals with persisting proteinuria as the baseline. Methods One hundred and fifty hard-working agricultural farmers from high-prevalence area for CKDu (Madawachchiya) were screened three times for proteinuria; 66 proteinuric and 21 non-proteinuric were identified as the baseline classification. Selected individuals were analysed further for creatinine, protein and cystatin C in urine and creatinine, cystatin C in serum. Urine protein-to-creatinine ratio (UP/UC) was calculated. Results Based on creatinine and cystatin C cut-off levels in serum, individuals were classified as high or normal. Diagnosis of two functional markers (creatinine and cystatin C) were evaluated using receiver operating characteristic (ROC) curve and in terms of sensitivity and specificity using UP/UC as the baseline. Creatinine and cystatin C-based eGFR (estimated Glomerular filtration rate) levels were calculated, and Pearson’s correlation coefficient was determined between different eGFR measurements using UP/UC. Mean (SD) UP/UC ratio, serum creatinine, and serum cystatin C levels of the proteinuric subjects were 129.0 (18.4) mg/mmol, 1.35 (0.39) mg/dL, 1.69 (0.58) mg/L. For non-proteniuric individuals, the results were found to be 14.4 (2.28), 1.22 (0.40) mg/dL, 0.82 (0.25) mg/L. The ROC analysis showed excellent accuracy in using cystatin C for identifying proteinuric patients than creatinine area under the curve (AUC): 0.9675, P < 0.001). Cut-off points were identified as 1.015 mg/dL for serum creatinine and 0.930mg/L for cystatin C. Furthermore, cystatin C based Hoek formula showed the better correlation (0.635, P < 0.001) with UP/UC compared with creatinine based modification of diet in renal disease (MDRD) formula. Conclusion The study showed elevated serum cystatin C in patients with persisting proteinuria compared with non-responding serum creatinine. Moreover, cystatin C-based eGFR equations were more accurate to determine the kidney function than serum creatinine in proteinuric patients who are vulnerable for CKDu in high-prevalence areas.
VSM a powerful diagnostic and planning tool for a successful Lean implementation: a Tunisian case study of an auto parts manufacturing firm*

Abstract For the past few years, many manufacturing organisations have been trying to get ‘lean’. A headlong rush to become lean also resulted in a scattered implementation of lean projects/tools often associated with a lack of a shared lean vision. This prevents them from effectively reaping the benefits of lean manufacturing paradigm. Meanwhile, many researchers and academics point out that any lean transformation initiative will be more effective if it starts by implementing Value Stream Mapping technique. However, little empirical work is available to provide real answers to practitioners on how to really apply Value Stream Mapping (VSM) as a diagnostic and planning tool. The experience of applying VSM in a real manufacturing case study has revealed that VSM has the capability to diagnose a manufacturing system with a lean perspective and to identify the opportunities for various lean projects/tools. The results demonstrate and validate authors’ finding that VSM is a good starting tool for transforming any enterprise into lean. They incite researchers/practitioners to start to enhance/extend their approach towards lean by integrating the standard VSM approach with additional lean tools to enable people not only to see but also to communicate and to manage their processes.
3-D Microvascular Imaging Using High Frame Rate Ultrasound and ASAP Without Contrast Agents: Development and Initial In Vivo Evaluation on Nontumor and Tumor Models

Three-dimensional imaging is valuable to noninvasively assess angiogenesis given the complex 3-D architecture of vascular networks. The emergence of high frame rate (HFR) ultrasound, which can produce thousands of images per second, has inspired novel signal processing techniques and their applications in structural and functional imaging of blood vessels. Although highly sensitive vascular mapping has been demonstrated using ultrafast Doppler, the detectability of microvasculature from the background noise may be hindered by the low signal-to-noise ratio (SNR) particularly in the deeper region and without the use of contrast agents. We have recently demonstrated a coherence-based technique, acoustic subaperture imaging (ASAP), for super-contrast vascular imaging and illustrated the contrast improvement using HFR contrast-enhanced ultrasound. In this work, we provide a feasibility study for microvascular imaging using ASAP without contrast agents, and extend its capability from 2-D to volumetric vascular mapping. Using an ultrasound research system and a preclinical probe, we demonstrated the improved visibility of microvascular mapping using ASAP in comparison to ultrafast power Doppler (PD) on a mouse kidney, liver, and tumor without contrast agent injection. The SNR of ASAP images improves in average by 10 dB when compared to PD. In addition, directional velocity mappings were also demonstrated by combining ASAP with the phase information extracted from lag-1 autocorrelation. The 3-D vascular and velocity mapping of the mouse kidney, liver, and tumor were demonstrated by stacking the ASAP images acquired using 2-D ultrasound imaging and a trigger-controlled linear translation stage. The 3-D results depicted clear microvasculature morphologies and functional information in terms of flow direction and velocity in two nontumor models and a tumor model. In conclusion, we have demonstrated a new 3-D in vivo ultrasound microvascular imaging technique with significantly improved SNR over existing ultrafast Doppler.
Growth-dependent drug susceptibility can prevent or enhance spatial expansion of a bacterial population

As a population wave expands, organisms at the tip typically experience plentiful nutrients while those behind the front become nutrient-depleted. If the environment also contains a gradient of some inhibitor (e.g. a toxic drug), a tradeoff exists: the nutrient-rich tip is more exposed to the inhibitor, while the nutrient-starved region behind the front is less exposed. Here we show that this can lead to complex dynamics when the organism’s response to the inhibitory substance is coupled to nutrient availability. We model a bacterial population which expands in a spatial gradient of antibiotic, under conditions where either fast-growing bacteria at the wave’s tip, or slow-growing, resource-limited bacteria behind the front are more susceptible to the antibiotic. We find that growth-rate dependent susceptibility can have strong effects on the dynamics of the expanding population. If slow-growing bacteria are more susceptible, the population wave advances far into the inhibitory zone, leaving a trail of dead bacteria in its wake. In contrast, if fast-growing bacteria are more susceptible, the wave is blocked at a much lower concentration of antibiotic, but a large population of live bacteria remains behind the front. Our results may contribute to understanding the efficacy of different antimicrobials for spatially structured microbial populations such as biofilms, as well as the dynamics of ecological population expansions more generally.
Managing Missing Data in the Hospital Survey on Patient Safety Culture: A Simulation Study.

BACKGROUND Case-wise analysis is advocated for the Hospital Survey on Patient Safety culture (HSOPS). OBJECTIVES Through a computer-intensive simulation study, we aimed to evaluate the accuracy of various imputation methods in managing missing data in the HSOPS. METHODS Using the original data from a cross-sectional survey of 5064 employees at a single university hospital in France, we produced simulation data on two levels. First, we resampled 1000 completed data based on the original 3045 complete responses using a bootstrap procedure. Second, missing values were simulated in these 1000 completed case data for comparison purposes, using eight different missing data scenarios. Third, missing values were imputed using five different imputation methods (1, random imputation; 2, item mean; 3, individual mean; 4, multiple imputation, and 5, sparse nonnegative matrix factorization. The performance for each imputation method was assessed using the root mean square error and dimension score bias. RESULTS The five imputation methods yielded close root mean square errors, with an advantage for the multiple imputation. The bias differences were greater regarding the dimension scores, with a clear advantage for multiple imputation. The worst performance was achieved by the mean imputation methods. DISCUSSION AND CONCLUSIONS We recommend the use of multiple imputation to handle missing data in HSOPS-based surveys, whereas mean imputation methods should be avoided. Overall, these results suggest the possibility of optimizing the HSOPS instrument, which should be reduced without loss of overall information.
A specific amino acid motif of HLA-DRB1 mediates risk and interacts with smoking history in Parkinson’s disease

Significance Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disease with both familial and sporadic forms and a clear genetic component. In addition, underlying immunoregulatory dysfunction and inflammatory processes have been implicated in PD pathogenesis. In this study, deep sequencing of HLA genes, which encode highly variable cell surface immune receptors, reveals specific variants conferring either risk or protection in PD. Because a history of cigarette smoking is known to be protective in PD, we analyzed the interaction of these genetic variants with smoking history in PD patients and healthy controls and found that the genetic effects are modified by history of cigarette smoking. These results provide a molecular model that explains the unique epidemiology of smoking in PD. Parkinson’s disease (PD) is a neurodegenerative disease in which genetic risk has been mapped to HLA, but precise allelic associations have been difficult to infer due to limitations in genotyping methodology. Mapping PD risk at highest possible resolution, we performed sequencing of 11 HLA genes in 1,597 PD cases and 1,606 controls. We found that susceptibility to PD can be explained by a specific combination of amino acids at positions 70–74 on the HLA-DRB1 molecule. Previously identified as the primary risk factor in rheumatoid arthritis and referred to as the “shared epitope” (SE), the residues Q/R-K/R-R-A-A at positions 70–74 in combination with valine at position 11 (11-V) is highly protective in PD, while risk is attributable to the identical epitope in the absence of 11-V. Notably, these effects are modified by history of cigarette smoking, with a strong protective effect mediated by a positive history of smoking in combination with the SE and 11-V (P = 10−4; odds ratio, 0.51; 95% confidence interval, 0.36–0.72) and risk attributable to never smoking in combination with the SE without 11-V (P = 0.01; odds ratio, 1.51; 95% confidence interval, 1.08–2.12). The association of specific combinations of amino acids that participate in critical peptide-binding pockets of the HLA class II molecule implicates antigen presentation in PD pathogenesis and provides further support for genetic control of neuroinflammation in disease. The interaction of HLA-DRB1 with smoking history in disease predisposition, along with predicted patterns of peptide binding to HLA, provide a molecular model that explains the unique epidemiology of smoking in PD.
Head cooling during sleep improves sleep quality in the luteal phase in female university students: A randomized crossover-controlled pilot study

Although selective head-cooling has been reported to decrease scalp and tympanic temperature and improve sleep quality, whether head-cooling during sleep can improve sleep quality in women during the luteal phase has not been elucidated. This randomized, controlled crossover open trial aimed to investigate the effect of head cooling during sleep on sleep quality in women during the luteal phase. Female university students aged 19–25 years with increased daytime sleepiness during the luteal phase were recruited by poster advertisement at their university from May to June 2016 and from May to June 2017. Fourteen women aged 19–22 years participated in this study. The temperature-controllable cooling sheet containing tubes filled with circulating water was used for head-cooling, and the head-cooling and the controlled temperature were set at 25°C and 35°C, respectively. Electroencephalogram data were obtained using a single-channel portable electroencephalogram device. The difference in sleep-related variables and tympanic temperature between head-cooling and control were analyzed using a linear mixed model. The proportion of arousal was lower with head cooling than with the control. In contrast, the proportion of non-REM3 and the delta power were higher with head cooling than with the control. The proportion of non-REM2 and non-REM3 among sleep EEG stages were positively and negatively correlated with the mean tympanic temperature during sleep, respectively. However, arousal and REM were not correlated with tympanic temperature. We considered the reduction of arousal time by head-cooling might be related to scalp temperature rather than tympanic temperature. Further, our results suggested that head-cooling also improved subjective sleep comfort. In conclusion, head-cooling during sleep could improve sleep quality in young women during the luteal phase.
Targeted interplay between bacterial pathogens and host autophagy

ABSTRACT Due to the critical role played by autophagy in pathogen clearance, pathogens have developed diverse strategies to subvert it. Despite previous key findings of bacteria-autophagy interplay, asystems-level insight into selective targeting by the host and autophagy modulation by the pathogens is lacking. We predicted potential interactions between human autophagy proteins and effector proteins from 56 pathogenic bacterial species by identifying bacterial proteins predicted to have recognition motifs for selective autophagy receptors SQSTM1/p62, CALCOCO2/NDP52 and MAP1LC3/LC3. Using structure-based interaction prediction, we identified bacterial proteins capable to modify core autophagy components. Our analysis revealed that autophagy receptors in general potentially target mostly genus-specific proteins, and not those present in multiple genera. The complementarity between the predicted SQSTM1/p62 and CALCOCO2/NDP52 targets, which has been shown for Salmonella, Listeria and Shigella, could be observed across other pathogens. This complementarity potentially leaves the host more susceptible to chronic infections upon the mutation of autophagy receptors. Proteins derived from enterotoxigenic and non-toxigenic Bacillus outer membrane vesicles indicated that autophagy targets pathogenic proteins rather than non-pathogenic ones. We also observed apathogen-specific pattern as to which autophagy phase could be modulated by specific genera. We found intriguing examples of bacterial proteins that could modulate autophagy, and in turn being targeted by autophagy as ahost defense mechanism. We confirmed experimentally an interplay between a Salmonella protease, YhjJ and autophagy. Our comparative meta-analysis points out key commonalities and differences in how pathogens could affect autophagy and how autophagy potentially recognizes these pathogenic effectors. Abbreviations: ATG5: autophagy related 5; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; GST: glutathione S-transferase; LIR: MAP1LC3/LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3 alpha; OMV: outer membrane vesicles; SQSTM1/p62: sequestosome 1; SCV: Salmonella containing vesicle; TECPR1: tectonin beta-propeller repeat containing 1; YhjJ: hypothetical zinc-protease.
A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion

Aberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva’s vertebrate ortholog, MFSD1, rescues the minerva mutant’s migration and T-antigen glycosylation defects. We thus identify a key conserved regulator that orchestrates O-glycosylation on a protein subset to activate a program governing migration steps important for both development and cancer metastasis.
Between Innate and Adaptive Immune Responses: NKG2A, NKG2C, and CD8+ T Cell Recognition of HLA-E Restricted Self-Peptides Acquired in the Absence of HLA-Ia

On healthy cells the non-classical HLA class Ib molecule HLA-E displays the cognate ligand for the NK cell receptor NKG2A/CD94 when bound to HLA class I signal peptide sequences. In a pathogenic situation when HLA class I is absent, HLA-E is bound to a diverse set of peptides and enables the stimulatory NKG2C/CD94 receptor to bind. The activation of CD8+ T cells by certain p:HLA-E complexes illustrates the dual role of this low polymorphic HLA molecule in innate and adaptive immunity. Recent studies revealed a shift in the HLA-E peptide repertoire in cells with defects in the peptide loading complex machinery. We recently showed that HLA-E presents a highly diverse set of peptides in the absence of HLA class Ia and revealed a non-protective feature against NK cell cytotoxicity mediated by these peptides. In the present study we have evaluated the molecular basis for the impaired NK cell inhibition by these peptides and determined the cell surface stability of individual p:HLA-E complexes and their binding efficiency to soluble NKG2A/CD94 or NKG2C/CD94 receptors. Additionally, we analyzed the recognition of these p:HLA-E epitopes by CD8+ T cells. We show that non-canonical peptides provide stable cell surface expression of HLA-E, and these p:HLA-E complexes still bind to NKG2/CD94 receptors in a peptide-restricted fashion. Furthermore, individual p:HLA-E complexes elicit activation of CD8+ T cells with an effector memory phenotype. These novel HLA-E epitopes provide new implications for therapies targeting cells with abnormal HLA class I expression.
Toxicity of Bacillus thuringiensis-Derived Pesticidal Proteins Cry1Ab and Cry1Ba against Asian Citrus Psyllid, Diaphorina citri (Hemiptera)

The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera), is an important pest of citriculture. The ACP vectors a bacterium that causes huanglongbing (HLB), a devastating and incurable disease of citrus. The bacterium Bacillus thuringiensis (Bt) produces multiple toxins with activity against a diverse range of insects. In efforts to provide additional control methods for the ACP vector of HLB, we identified pesticidal proteins derived from Bt for toxicity against ACP. The trypsin proteolytic profiles of strain-derived toxins were characterized. Strain IBL-00200, one of six strains with toxins shown to have basal activity against ACP was selected for liquid chromatography-mass spectrometry (LC-MS/MS) identification of the individual Cry toxins expressed. Toxicity assays with individual toxins derived from IBL-00200 were then performed. The activated form of the Cry toxins Cry1Ab and Cry1Ba were toxic to ACP with LC50 values of approximately 120 µg/mL. Disruption of the midgut epithelium was associated with the toxicity of both the IBL-00200-derived toxin mixture, and with Cry1Ba. With further optimization of the efficacy of Cry1Ab and Cry1Ba, these toxins may have practical utility against ACP. Bt toxins with activity against ACP may provide an additional tool for management of ACP and the associated HLB disease, thereby providing a more sustainable and environmentally benign approach than repeated application of broad-spectrum insecticides.
Investigating Narcissistic Personality Traits in the Context of Positive Psychotherapy.

Introduction The purpose of the current study is to elucidate the relationships between narcissistic personality traits and primary and secondary capacities of individuals within the context of positive psychotherapy. Methods In the study conducted in 2016-17 academic year, the participants were 255 university students (51.4% female, n=124 and 48.6% male, n=124) aged 18 to 25. As data collection tools, the Narcissistic Personality Inventory, Wiesbaden's Inventory of Positive Psychotherapy and Family Therapy and Demographic Information Form created by the researchers were used. The Multiple Regression Analysis method was employed to achieve the objectives of the study. Results The findings revealed that two of the primary capacities, namely time and patience, were significant predictors of narcissism. In other words, the time capacity was a positive significant predictor of narcissistic personality traits, while those traits were predicted by the patience capacity in a negative way. Regarding the secondary capacities, politeness, faithfulness, cleanliness and honesty were significant predictors of narcissistic personality traits. In brief, the faithfulness, cleanliness and honesty capacities were positive significant predictors whereas the politeness capacity was a negative significant predictor of narcissistic personality traits. Conclusion In brief, the primary and secondary capacities, which are defined as personality traits in positive psychotherapy, were significant predictors of narcissistic personality traits. Results and implications are discussed in the light of relevant literature, and suggestions are offered for future research.
Template growth of Au/Ag nanocomposites on phosphorene for sensitive SERS detection of pesticides

We report template growth and dense packing of noble metallic nanoparticles (NPs) on few-layer phosphorene for sensitive surface-enhanced Raman scattering (SERS) detection. Phosphorene obtained by electrochemical exfoliation serves as both the template and reductant in the fabrication of noble metallic NPs which are dispersed on phosphorene without aggregation or pile-up. The BP/Ag/Au and BP/Au/Ag nanocomposites with a nanogap structure exhibit excellent SERS sensitivity and reproducibility with respect to Rhodamine 6G. The BP/Au/Ag nanocomposite is further utilized as the SERS substrate for the detection of two fungicides, thiabendazole and thiram, and detection limits of 10–7 and 10–8 M are achieved. Template growth of Au/Ag nanocomposites is demonstrated to be a green strategy for the fabrication of SERS substrates and has large potential in applications such as pesticide detection.