Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasma Cell Vulvitis: A Systematic Review of Interventions

Objectives Plasma cell vulvitis (PCV) is a rare chronic inflammatory disorder, where the symptoms can be severe and may affect patient's quality of life. However, there are currently no evidence-based treatment guidelines. The aims of this systematic review were to evaluate efficacy of individual treatments and to inform future research. Materials and Methods A systematic search was conducted of publication between 1952 and August 2020 via MEDLINE, Embase, and Emcare. All publications that evaluated the efficacy of treatments for patients with PCV were included. Forty-seven publications comprising 45 case reports and case series and 2 cohort studies were included. Results To date, there are no randomized controlled trials evaluating the efficacy of different treatment options. There are also no studies that assess the impact of treatment on quality of life. Topical corticosteroids are the most frequently used first-line therapy, with limited evidence to support their efficacy, followed by topical imiquimod and surgical excision. The least supported intervention is cryotherapy. Conclusions Although descriptive studies support the use of topical corticosteroids and, to a lesser degree, topical calcineurin inhibitors and imiquimod, this review highlights the need for standardized outcome measures and randomized clinical trials for more definitive therapeutic recommendations for women with PCV.
Effectiveness and safety of Liuhedan for treating cellulitis

Abstract Background: Liuhedan is a famous traditional Chinese Medicine formula used to treat cellulitis in China. However, there are no systematic reviews for the evidence and the therapeutic effectiveness and safety of Liuhedan for treating cellulitis. The aim of this study is to summarize previous evidence, assessing the efficacy and safety of Liuhedan treating cellulitis. Methods: We will search the EMBASE, WANFANG DATA, Web of Knowledge, CNKI, PubMed, ClinicalTrials.gov, and Cochrane Library from inception to June 30, 2021 to retrieve relevant studies using the search strategy: (“Liuhedan” OR “Liuhe Pill” OR “Liu-He-Dan”) AND (“cellulitis” OR “phlegmon” OR “skin and soft tissue infection” OR “skin tissue infection” OR “soft tissue infection”). Two authors independently judged study eligibility and extracted data. Heterogeneity will be examined by computing the Q statistic and I2 statistic. Results: This study assessed the efficiency and safety of Liuhedan for treating cellulitis. Conclusions: This study will provide reliable evidence-based evidence for the clinical application of Liuhedan for treating cellulitis. Ethics and dissemination: Ethical approval is unnecessary as this protocol is only for systematic review and does not involve privacy data. The findings of this study will be disseminated electronically through a peer-review publication or presented at a relevant conference.
Estimation of renal function by three CKD-EPI equations in Chinese HIV/AIDS patients

Abstract Assessing renal function accurately is important for human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) patients. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recommended three equations to calculate estimated glomerular filtration rate (eGFR). There is evidence that eGFR based on the combination of serum creatinine and cystatin C is the most accurate of the three equations. But there is limited data on the comparison of three CKD-EPI equations in Chinese HIV/AIDS patients. The aim of our study was to compare the three CKD-EPI equations in Chinese HIV/AIDS population and assess renal function. Cross-sectional, single center, prospective study. One hundred seventy two Chinese adult HIV/AIDS patients were enrolled, including 145 (84.3%) males and 27 (15.7%) females. Mean age was 40(±12) years old. Overall mean eGFR based on serum creatinine, cystatin C and the combination of the 2 markers was 112.6(±19.0) mL/min/1.73 m2, 92.0(±24.2)mL/min/1.73 m2, and 101.7(±21.8)mL/min/1.73 m2, respectively (P = .000). The eGFR calculated by serum creatinine alone is higher than eGFR calculated by combination of serum creatinine and cystatin C, and eGFR calculated by cystatin C individual is lower than eGFR calculated by combination of the 2 markers. Of the 3 CKD-EPI equations, the CKD-EPIscr-cys equation may have the most accuracy in evaluating renal function in Chinese HIV/AIDS patients while the CKD-EPIscr equation may overestimate renal function and the CKD-EPIcys equation may underestimate renal function.
Comparison of polypeptides that bind the transferrin receptor for targeting gold nanocarriers

The ability to target therapeutic agents to specific tissues is an important element in the development of new disease treatments. The transferrin receptor (TfR) is one potential target for drug delivery, as it expressed on many dividing cells and on brain endothelium, the key cellular component of the blood-brain barrier. The aim of this study was to compare a set of new and previously-described polypeptides for their ability to bind to brain endothelium, and investigate their potential for targeting therapeutic agents to the CNS. Six polypeptides were ranked for their rate of endocytosis by the human brain endothelial cell line hCMEC/D3 and the murine line bEnd.3. One linear polypeptide and two cyclic polypeptides showed high rates of uptake. These peptides were investigated to determine whether serum components, including transferrin itself affected uptake by the endothelium. One of the cyclic peptides was strongly inhibited by transferrin and the other cyclic peptide weakly inhibited. As proof of principle the linear peptide was attached to 2nm glucose coated gold-nanoparticles, and the rate of uptake of the nanoparticles measured in a hydrogel model of the blood-brain barrier. Attachment of the TfR-targeting polypeptide significantly increased the rates of endocytosis by brain endothelium and increased movement of nanoparticles across the cells.
Circadian misalignment by environmental light/dark shifting causes circadian disruption in colon

Background Physiological circadian rhythms (CRs) are complex processes with 24-hour oscillations that regulate diverse biological functions. Chronic weekly light/dark (LD) shifting (CR disruption; CRD) in mice results in colonic hyperpermeability. However, the mechanisms behind this phenomenon are incompletely understood. One potential innovative in vitro method to study colonic CRs are colon organoids. The goals of this study were to utilize circadian clock gene Per2 luciferase reporter (Per2::Luc) mice to measure the effects of chronic LD shifting on colonic tissue circadian rhythmicity ex vivo and to determine if organoids made from shifted mice colons recapitulate the in vivo phenotype. Methods Non-shifted (NS) and shifted (S) BL6 Per2::Luc mice were compared after a 22-week experiment. NS mice had a standard 12h light/12h dark LD cycle throughout. S mice alternated 12h LD patterns weekly, with light from 6am-6pm one week followed by shifting light to 6pm-6am the next week for 22 weeks. Mice were tested for intestinal permeability while colon tissue and organoids were examined for CRs of bioluminescence and proteins of barrier function and cell fate. Results There was no absolute difference in NS vs. S 24h circadian period or phase. However, chronic LD shifting caused Per2::Luc S mice colon tissue to exhibit significantly greater variability in both the period and phase of Per2::Luc rhythms than NS mice colon tissue and organoids. Chronic LD shifting also resulted in increased colonic permeability of the Per2::Luc mice as well as decreased protein markers of intestinal permeability in colonic tissue and organoids from shifted Per2:Luc mice. Conclusions Our studies support a model in which chronic central circadian disruption by LD shifting alters the circadian phenotype of the colon tissue and results in colon leakiness and loss of colonic barrier function. These CRD-related changes are stably expressed in colon stem cell derived organoids from CRD mice.
Compliance Testing and Homogenous Exposure Group Assessment in the South African Coal Mining Industry.

OBJECTIVES Globally, several strategies for compliance testing and within-group exposure variability have been suggested. This study aimed to evaluate the performance of the South African Mining Industry Code of Practice (SAMI CoP) approach for grouping and compliance testing against international standards. METHODS A total of 28 homogenous exposure groups (HEGs) with 728 underground coal mine workers' eight-hour time-weighted average coal dust concentration data were obtained. Compliance testing was assessed using 10% exceedance above occupational exposure limit (OEL) for SAMI CoP, and the 95th percentile of the lognormal distribution was computed for the European Standardization Committee (CEN) and American Industrial Hygiene Association (AIHA). Comparison of the homogeneity of the HEGs was done between SAMI CoP which mandates that both the arithmetic mean (AM) and 90th percentile must fall in the same exposure band to certify homogeneity and the global geometric standard deviation (GSD) and Rappaport ratio (R-ratio) with specific acceptability criteria. To test the homogeneity of exposure within job titles, eight non-homogenous HEGs that have two or more job titles with three measurements were investigated using GSD and the SAMI CoP criteria. RESULTS A total of 21 HEGs out of 28 were non-compliant to the OEL across SAMI CoP, CEN, and AIHA criteria. Compliance to the OEL was observed for seven HEGs according to the SAMI CoP approach, whereas only one HEG was compliant according to both the SAMI CoP and CEN approaches. The GSD criterion and SAMI CoP revealed that 11 and 6 HEGs were homogenous, respectively, and only on 4 occasions, the 2 approaches agreed. The job titles of the majority of non-homogenous HEGs in both SAMI CoP and GSD were actually homogenous. Five out of 10 sub-groups have their AM above that of HEG B. Other HEGs had at least one of their AM and 90th percentile values above that of their respective parent HEGs. CONCLUSIONS All three approaches mainly confirmed non-compliance of HEGs. SAMI CoP tended to show compliance of HEGs more than CEN. Non-homogenous HEGs had many job titles that were homogenous according to both SAMI CoP and GSD criteria. There was no perfect agreement of homogeneity by all the indicators. For both future constitutions of HEGs as well as a retrospective assessment of high exposure groups, homogeneity can be improved by using job titles.
The risk of colorectal neoplasm in ex- and never-smokers according to urinary cotinine level

Abstract To investigate the relationship between urinary cotinine and colorectal neoplasm (CRN). The participants in the health screening cohort of the National Cancer Center who underwent screening colonoscopy between June 2007 and December 2009 were included. A total of 8121 subjects who underwent urinary cotinine measurement within 14 days from the index colonoscopy were included. Cotinine positivity was defined as having a urinary cotinine level ≥50 ng/mL. Follow-up colonoscopy data were collected by reviewing the patients’ medical records. Patients were classified according to their urinary cotinine level and self-reported smoking status, and the number of patients with cotinine positivity was 1960 (24.1%). There was no significant difference in the cumulative CRN and advanced CRN (ACRN) risks according to the self-reported smoking status. However, cotinine positivity at the time of index colonoscopy was an independent risk factor for CRN (hazard ratio [HR]= 1.23, P = .006) in follow-up colonoscopy. Moreover, in never- and ex-smokers, cotinine positivity was an independent risk factor for CRN (HR = 1.95, P = .019; HR = 2.12, P = .003, respectively) and ACRN (HR = 8.89, P < .001; HR = 5.03, P = .003) during follow-up colonoscopy. The cumulative incidence of CRN and ACRN was higher in the cotinine-positive never- and ex-smokers than in the cotinine-negative never- and ex-smokers (P < .001 and P = .008, respectively). CRN or ACRN is more likely to occur at follow-up colonoscopy in the urinary cotinine-positive never- and ex-smokers than in the urinary cotinine-negative group. Therefore, urinary cotinine measurements may provide useful information on never- or ex-smokers undergoing screening colonoscopy.
Prognostic value of serum bilirubin in patients with heart failure

Abstract Background: Heart failure (HF) is one of the common and critical disease, and often accompanied by increased level of serum bilirubin, but the role of an indicator of bilirubin to monitor the prognosis of patients with heart failure is still unclear, so we implemented the study to systematically evaluate the predictive value of bilirubin in HF. Methods: A comprehensive search and systematic review will be conducted on electronic databases such as Medline, Cochrane Library, Embase, Web of Science, Cochrane Clinical Trials Database of study on the relationship between bilirubin and prognosis of HF patients. Review Manager software (version 5.3.5) and STATA 14 software (version 14.0) will be used for data analysis and synthesis. Results: The results will systematically and comprehensively reveal the evidence on the predictive value of bilirubin in HF. Conclusion: The study will display the effect of bilirubin level on the prognosis of patients with heart failure, and help clinicians to pay more attention to the level of bilirubin in patients with HF, and can take certain treatment measures as earlier as possible. Inplasy registration number: INPLASY202140116.
Top- Partial Label Machine

To deal with ambiguities in partial label learning (PLL), the existing PLL methods implement disambiguations, by either identifying the ground-truth label or averaging the candidate labels. However, these methods can be easily misled by the false-positive labels in the candidate label set. We find that these ambiguities often originate from the noise caused by highly correlated or overlapping candidate labels, which leads to the difficulty in identifying the ground-truth label on the first attempt. To give the trained models more tolerance, we first propose the top-<inline-formula> <tex-math notation="LaTeX">$k$ </tex-math></inline-formula> partial loss and convex top-<inline-formula> <tex-math notation="LaTeX">$k$ </tex-math></inline-formula> partial hinge loss. Based on the losses, we present a novel top-<inline-formula> <tex-math notation="LaTeX">$k$ </tex-math></inline-formula> partial label machine (TPLM) for partial label classification. An efficient optimization algorithm is proposed based on accelerated proximal stochastic dual coordinate ascent (Prox-SDCA) and linear programming (LP). Moreover, we present a theoretical analysis of the generalization error for TPLM. Comprehensive experiments on both controlled UCI datasets and real-world partial label datasets demonstrate that the proposed method is superior to the state-of-the-art approaches.
Supplemental Materials: Deep denoising for multi-dimensional synchrotron X-ray tomography without high-quality reference data

X-ray tomography datasets were acquired at the TOMCAT beamline at the Swiss Light Source (SLS) at the Paul Scherrer Institut (PSI), Villigen, Switzerland. In addition, an X-ray diffraction tomography (XRD-CT) dataset was acquired at the ID15A beamline at the European Synchrotron (ESRF), Grenoble, France. Static X-ray 3D micro-tomography The data was acquired at the TOMCAT beamline1, and is publicly available2. The dataset contained 1001 projection images across an angular range of 180° measuring 1100×1440 square pixels of size 2.75 μm. The acquisition took 1s, the exposure time was 1ms, and the mean energy of the polychromatic beam was 30keV. Dynamic X-ray micro-tomography This dataset was acquired at the TOMCAT beamline1, and is publicly available2. A full scan was performed every 0.1s, resulting in a dataset of 180 time steps spanning approximately 32 seconds, divided into three 6s chunks with 7s pauses in between. Each time step contained 300 projection images across an angular range of 180° measuring 1100×1440 square pixels of size 2.75 μm. The mean energy of the polychromatic beam was 30keV. The documented angular increment was π/300 radians, consistent with the acquisition of 300 projection images per half rotation2. We observed a small deviation in this case. The angular increment was π/299.924, which could be determined up to five significant digits by visual inspection of the combined GridRec reconstruction of several time steps. XRD-CT High-energy X-ray diffraction measurements were taken at the ID15A beamline using a monochromatic pencil beam (90keV energy). Data was collected of 3 horizontal slices, spaced 7mm apart, and acquisition of each slice took 20 minutes. Acquisition was performed in 273 translation steps over a scan range of 12mm and in 225 rotational steps over an angular range of 180°. Sinograms were computed from the acquired images using the pyFAI library3. A subset of the sinograms was selected, containing 3 horizontal slices with 11 channels each. The displayed FBP reconstructions were computed with the Shepp-Logan filter using the ASTRA-toolbox4.
Toxicogenicity and mechanistic pathways of aflatoxin B1 induced renal injury

The study investigated the toxicogenic effects, molecular mechanisms and proteomic assessment of aflatoxin B1 (AFB1) on human renal cells. Hek293 cells were exposed to AFB1 (0–100 μM) for 24 h. The effect on cell viability was assessed using the methylthiazol tetrazolium (MTT) assay, which also produced the half maximal inhibitory concentration (IC50) used in subsequent assays. Free radical production was evaluated by quantifying malondialdehyde (MDA) and nitrate concentration, while DNA fragmentation was determined using the single cell gel electrophoresis (SCGE) assay and DNA gel electrophoresis. Damage to cell membranes was ascertained using the lactate dehydrogenase (LDH) assay. The concentration of ATP, reduced glutathione (GSH), necrosis, annexin V and caspase activity was measured by luminometry. Western blotting and quantitative PCR was used to assess the expression of proteins and genes associated with apoptosis and oxidative stress. The MTT assay revealed a reduction in cell viability of Hek293 cells as the AFB1 concentration was increased, with a half maximum inhibitory concentration (IC50) of 32.60 μM. The decreased viability corresponded to decreased ATP concentration. The upregulation of Hsp70 indicated that oxidative stress was induced in the AFB1‐treated cells. While this implies an increased production of free radicals, the accompanying upregulation of the antioxidant system indicates the activation of defense mechanisms to prevent cellular damage. Thus, membrane damage associated with increased radical formation was prevented as indicated by the reduced LDH release and necrosis. In addition, cytotoxic effects were evident as AFB1 activated the intrinsic pathway of apoptosis with corresponding increased DNA fragmentation, p53 and Bax upregulation and increased caspase activity, but externalization of phosphatidylserine (PS), a major hallmark of apoptosis, did not occur in AFB1 treated renal cells. The results suggest that AFB1 induced oxidative stress leading to cell death by the intrinsic pathway of apoptosis in renal cells.
CD44 alternative splicing senses intragenic DNA methylation in tumors via direct and indirect mechanisms

Abstract DNA methylation (meDNA) is a modulator of alternative splicing, and splicing perturbations are involved in tumorigenesis nearly as frequently as DNA mutations. However, the impact of meDNA on tumorigenesis via splicing-mediated mechanisms has not been thoroughly explored. Here, we found that HCT116 colon carcinoma cells inactivated for the DNA methylases DNMT1/3b undergo a partial epithelial to mesenchymal transition associated with increased CD44 variant exon skipping. These skipping events are directly mediated by the loss of intragenic meDNA and the chromatin factors MBD1/2/3 and HP1γ and are also linked to phosphorylation changes in elongating RNA polymerase II. The role of meDNA in alternative splicing was confirmed by using the dCas9/DNMT3b tool. We further tested whether the meDNA level could have predictive value in the MCF10A model for breast cancer progression and in patients with acute lymphoblastic leukemia (B ALL). We found that a small number of differentially spliced genes, mostly involved in splicing and signal transduction, are correlated with the local modulation of meDNA. Our observations suggest that, although DNA methylation has multiple avenues to affect alternative splicing, its indirect effect may also be mediated through alternative splicing isoforms of these meDNA sensors.
Admixed phenotype of NEDD4L associated periventricular nodular heterotopia

Supplemental Digital Content is available in the text Abstract Rationale: Periventricular nodular heterotopia-7 (PVNH7) is a neurodevelopmental disorder associated with improper neuronal migration during neurogenesis in cortex development caused by pathogenic variants in the NEDD4L gene. Patient concerns: We report the case of a polystigmatized 2-year-old boy having significant symptomatologic overlap with PVNH7, such as delayed psychomotor and mental development, seizures and infantile spasms, periventricular nodular heterotopia, polymicrogyria, cleft palate, 2 to 3 toe syndactyly, hypotonia, microretrognathia, strabismus, and absent speech and walking. The patient showed also distinct symptoms falling outside PVNH7 symptomatology, also present in the proband's older brother, such as blue sclerae, hydronephrosis, transversal palmar crease (found also in their father), and bilateral talipes equinovarus. In addition, the patient suffered from many other symptoms. Diagnoses: The boy, his brother and their parents were subjected to whole-exome sequencing. Because of uncertainties in symptomatology and inheritance pattern, the top-down approach was hard to apply. Using the bottom-up approach, we identified a known pathogenic variant, NM_001144967. 2(NEDD4L):c.2677G>A:p.Glu893Lys, in the proband's genome that absented in any other analyzed family member, suggesting its de novo origin. Interventions and outcomes: The patient was treated with Convulex 300 mg/mL for the successful seizure control and Euthyrox 25mg for the treatment of thyroid malfunction. He also took various supplements for the metabolism support and digestion regulation. Moreover, the patient underwent the corrective surgeries of cleft palate and talipes equinovarus. Lessons: We successfully identified the causative mutation NM_001144967. 2(NEDD4L):c.2677G>A:p.Glu893Lys explaining symptoms overlapping those reported for PVNH7. Symptoms shared with the brother were not explained by this variant, since he was not a carrier of the pathogenic NEDD4L variant. These are most likely not extended phenotypes of PVNH7, rather an independent clinical entity caused by a yet unidentified genetic factor in the family, highlighting thus the importance of thorough evaluation of symptomatology and genomic findings in affected and unaffected family members, when such data are available.