Miracle-dz/UniFAR-FTUs huggingface dataset:
An altered secretome is an early marker of the pathogenesis of CLN6 Batten disease

Neuronal ceroid lipofuscinoses (NCLs) are a group of inherited childhood neurodegenerative disorders. In addition to the accumulation of auto‐fluorescent storage material in lysosomes, NCLs are largely characterised by region‐specific neuroinflammation that can predict neuron loss. These phenotypes suggest alterations in the extracellular environment—making the secretome an area of significant interest. This study investigated the secretome in the CLN6 (ceroid‐lipofuscinosis neuronal protein 6) variant of NCL. To investigate the CLN6 secretome, we co‐cultured neurons and glia isolated from Cln6nclf or Cln6± mice, and utilised mass spectrometry to compare protein constituents of conditioned media. The significant changes noted in cathepsin enzymes, were investigated further via western blotting and enzyme activity assays. Viral‐mediated gene therapy was used to try and rescue the wild‐type phenotype and restore the secretome—both in vitro in co‐cultures and in vivo in mouse plasma. In Cln6nclf cells, proteomics revealed a marked increase in catabolic and cytoskeletal‐associated proteins—revealing new similarities between the pathogenic signatures of NCLs with other neurodegenerative disorders. These changes were, in part, corrected by gene therapy intervention, suggesting these proteins as candidate in vitro biomarkers. Importantly, these in vitro changes show promise for in vivo translation, with Cathepsin L (CTSL) activity reduced in both co‐cultures and Cln6nclf plasma samples post gene‐therapy. This work suggests the secretome plays a role in CLN6 pathogenesis and highlights its potential use as an in vitro model. Proteomic changes present a list of candidate biomarkers for monitoring disease and assessing potential therapeutics in future studies.
Systematic review of safety and efficacy of belimumab in treating immune‐mediated disorders

Biologic agents (also termed biologics or biologicals) are becoming increasingly important in the treatment of immune‐mediated diseases. However, the diversity of clinical trials along with the fast pace of publication makes it difficult to determine the level of evidence for the use of a biologic for a given disorder. To address this challenge, we are publishing a series of systematic reviews evaluating the safety and efficacy of B cell–targeting biologics for the treatment of immune‐mediated diseases. In this article, we have assessed the safety and efficacy of belimumab, a fully human IgG1 monoclonal antibody targeting the cytokine B cell–activating factor (BAFF).
Comparing neuropathy in multiple myeloma and AL amyloidosis

Peripheral neuropathy (PN) is frequent in patients with monoclonal gammopathy due to plasma cell dyscrasia, but little is known about the comparative impact of nerve dysfunction in different disorders. We compared clinical and laboratory results between two diagnostic groups. We recruited 76 untreated multiple myeloma (MM) and 27 AL amyloidosis (ALA) patients for evaluation of symptoms, clinical findings and nerve conduction studies (NCS). We diagnosed significant PN using total neuropathy scores (TNS > 7) in 17.6% of MM and 48.1% of ALA patients and in 27.7% of MM and 35.7% of ALA patients using NCS findings. TNS score grades were significantly higher in the AL amyloidosis patients (Fisher's exact test: P = .02) but a NCS based PN diagnosis was not significantly different (Fisher's exact test: P = .13). A significantly higher TNS vibration (P = .04) and pin (P = .02) sensory sign and TNS reflex (P = .04) sign score was found in amyloidosis patients. Likewise, quantitative sensory thresholds for vibration was higher in amyloidosis patients (Welsh ANOVA: P = .01). NCS revealed signs of more frequent axonal tibial neuropathy with significantly lower motor response amplitudes (P = .02) and resulting higher TNS scores (P = .002), while sural nerve sensory response amplitudes were without significant difference (P = .86). We found more severe TNS grades of PN in AL amyloidosis patients compared with MM patients. We also found higher sensory symptoms scores and higher thresholds for vibration but similar sensory involvement using NCS. The NCS exclusively showed signs of an axonal neuropathy.
Memory at Play: Examining Relations Between Episodic and Semantic Memory in a Children's Museum.

The relation between episodic and semantic memory was examined by testing how semantic knowledge influences children's episodic memory for events and their locations. Five-, six-, and seven-year-olds (N = 87) engaged in events in a children's museum designed as a town. Events were semantically congruent or incongruent with the spatial location (e.g., sorting mail at post office vs. grocery store). In addition to this experimental paradigm, a semantic interview assessed children's semantic knowledge about real-world locations. Accuracy in the experimental paradigm showed that children's semantic memory influenced memory for locations. Interviews revealed age-related improvements in children's semantic knowledge. Regression analyses examined factors that best supported episodic memory. These results provide novel insights and highlight the utility of research in naturalistic settings.
Effective supervision of doctoral students in public and population health in Africa: CARTA supervisors’ experiences, challenges and perceived opportunities

ABSTRACT The quality and success of postgraduate education largely rely on effective supervision. Since its inception in 2008, the Consortium for Advanced Research Training in Africa (CARTA) has been at the forefront of providing training to both students and supervisors in the field of public and population health. However, there are few studies on supervisors’ perceptions on effective doctoral supervision. We used a mostly descriptive study design to report CARTA-affiliated doctoral supervisors’ reflections and perceptions on doctoral supervision, challenges and opportunities. A total of 77 out of 160 CARTA supervisors’ workshop participants responded to the evaluation. The respondents were affiliated with 10 institutions across Africa. The respondents remarked that effective supervision is a two-way process, involving both supervisor and supervisee’s commitment. Some reported that the requirements for effective supervision included the calibre of the PhD students, structure of the PhD programme, access to research infrastructure and resources, supervision training, multidisciplinary exposure and support. Male supervisors have significantly higher number of self-reported PhD graduates and published articles on Scopus but no difference from the females in h-index. We note both student and systemic challenges that training institutions may pursue to improve doctoral supervision in Africa.
Quantitative detection of SARS‐CoV‐2 RNA in nasopharyngeal samples from infected patients with mild disease

Diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS‐COV‐2) cases is based on the count of real‐time reverse transcription‐plymerase chain reaction (RT‐PCR) positive people. Viral load by real‐time RT‐PCR has been suggested as a biomarker of the SARS‐CoV‐2 infection. However, the association of viral load and severity of the disease is not yet resolved. Nasopharyngeal samples from 458 patients were tested by RT‐PCR for SARS‐CoV‐2 diagnosis. Relative quantitation was made by the comparative threshold cycle (ΔΔCt) formula between ORF1ab viral and RNase P housekeeping genes. Absolute viral load was calculate using a reference positive control. Most prevalent clinical signs were cough (75.8%), myalgia (66.7%), and fever (48.5%). Hypertension (18.2%), neurological diseases (15.1%), and asthma and hypothyroidism (12.1%) were most frequent comorbidities. Fever, either as an exclusive symptom or combined with others, was associated with high viral loads ( 2 ‐ ∆ ∆ C t range, 35.65–155.16; 4.25–4.89 log10 RNA copies/test]). During the first week after onset of symptoms in mild patients up to 60 years‐old was detected the peak of viral load. Children under 10 years old have a high viral load (313.84; 2.50) in the first 2 days postinfection with a sharp decline thereafter. Cases between 10 and 49 years old mostly showed low and moderate viral load during the first 2 days postinfection (range, 0.03 to 17.24; −1.50 to 1.24). Patients over 60 years old have high viral load up to the second week after the onset of symptoms (range, 25.32–155.42; 1.40–2.19), indicating the longer presence of the virus in them. These findings suggest the viral load in nasopharyngeal swabs would help to monitor the SARS‐CoV‐2 infection in mild coronavirus disease 2019 cases.
Comparing methods for estimating patient‐specific treatment effects in individual patient data meta‐analysis

Meta‐analysis of individual patient data (IPD) is increasingly used to synthesize data from multiple trials. IPD meta‐analysis offers several advantages over meta‐analyzing aggregate data, including the capacity to individualize treatment recommendations. Trials usually collect information on many patient characteristics. Some of these covariates may strongly interact with treatment (and thus be associated with treatment effect modification) while others may have little effect. It is currently unclear whether a systematic approach to the selection of treatment‐covariate interactions in an IPD meta‐analysis can lead to better estimates of patient‐specific treatment effects. We aimed to answer this question by comparing in simulations the standard approach to IPD meta‐analysis (no variable selection, all treatment‐covariate interactions included in the model) with six alternative methods: stepwise regression, and five regression methods that perform shrinkage on treatment‐covariate interactions, that is, least absolute shrinkage and selection operator (LASSO), ridge, adaptive LASSO, Bayesian LASSO, and stochastic search variable selection. Exploring a range of scenarios, we found that shrinkage methods performed well for both continuous and dichotomous outcomes, for a variety of settings. In most scenarios, these methods gave lower mean squared error of the patient‐specific treatment effect as compared with the standard approach and stepwise regression. We illustrate the application of these methods in two datasets from cardiology and psychiatry. We recommend that future IPD meta‐analysis that aim to estimate patient‐specific treatment effects using multiple effect modifiers should use shrinkage methods, whereas stepwise regression should be avoided.
A Novel Class of Betaine-Type Polyampholytes with Stimuli-Responsive and Complexing Properties

Linear and crosslinked betaine-type polyampholytes based on ethyl 3-amincrotonate and saturated carboxylic acids have been synthesized by very fast polymerization in bulk and solution. Bulk polymerization occurred exothermically even at room temperature and without adding an initiator. The polyampholytes showed stimuli-responsive properties with respect to pH, ionic strength, water/organic solvent mixtures, and metal ion complexation.
Validity Assessment of Self-reported Medication Use for Hypertension, Diabetes, and Dyslipidemia in a Pharmacoepidemiologic Study by Comparison With Health Insurance Claims

Background Although self-reported questionnaires are widely employed in epidemiologic studies, their validity has not been sufficiently assessed. The aim of this study was to evaluate the validity of a self-reported questionnaire on medication use by comparison with health insurance claims and to identify individual determinants of discordance in the Tsuruoka Metabolomics Cohort Study. Methods Participants were 2,472 community-dwellers aged 37 to 78 years from the Tsuruoka Metabolomics Cohort Study. Information on lifestyle and medications was collected through a questionnaire. Sensitivity and specificity were determined using health insurance claims from November 2014 to March 2016, which were used as a standard. Potential determinants of discordance were assessed using multivariable logistic regression. Results The self-reported questionnaire on medication use showed high validity. Sensitivity and specificity were 0.95 (95% CI, 0.93–0.96) and 0.97 (95% CI, 0.96–0.98) for antihypertensive medications, 0.94 (95% CI, 0.91–0.97) and 0.98 (95% CI, 0.98–0.99) for diabetes medications, and 0.84 (95% CI, 0.82–0.87) and 0.98 (95% CI, 0.97–0.99) for dyslipidemia medications, respectively. Males without high education and those who currently smoke cigarettes were found to be associated with discordant reporting which affected sensitivity, especially those with medication use for dyslipidemia. Conclusions In this population-based cohort study, we found that the self-reported questionnaire on medication use was a valid measure to capture regular medication users. Sensitivity for dyslipidemia medications was lower than those for the other medications. Type of medication, sex, education years, and smoking status influenced discordance, which affected sensitivity in self-reporting.
Experimental determination of the refractivity virial coefficients of atomic gases

Values of the second refractivity virial coefficients BR of the atomic gases He, Ne, Ar, Kr, and Xe have been measured with a recently improved differential‐interferometric technique to a high degree of accuracy. This device basically consists of two coupled grating interferometers. One interferometer, with two similar cells in series, measures differentially the higher‐order effects of density while the second interferometer, with two similar cells in parallel, simultaneously measures the absolute value of the refractive index. In the range of pressure investigated (up to 40 MPa), the third refractivity virial coefficient CR becomes significant for the gases Ar, Kr, and Xe and the fourth refractivity virial coefficient DR becomes significant for Xe. The agreement between our experimental BR and the theoretical prediction based on the classical dipole–induced‐dipole model is fairly good for Ar, Kr, and Xe but poor for He and Ne. For He and Ne, however, good agreement is obtained when a semiclassical appro.
Pancreatic Cancer: A Review of Risk Factors, Diagnosis, and Treatment

This review aims to summarize the latest knowledge on factors, diagnosis, and treatment of pancreatic cancer, and aims to promote further research on this under-studied malignant tumor. At present, we urgently need to identify high-risk patients with precancerous diseases through screening approaches, so that medical professionals and the general public may better understand prevention strategies or early detection measures. Pancreatic cancer is a highly invasive malignant tumor with a fatal risk, mainly seen in men and older adults (60-85 years old). Pancreatic cancer is now increasingly observed in young patients. Because the disease has no early symptoms and can quickly invade surrounding tissues and organs, it is one of the deadliest cancers. With a view to identify the important factors for the development of pancreatic cancer, previous studies have found that smoking, alcohol, and chronic pancreatitis are considered high-risk factors. Recent studies have shown that abnormal metabolism of human microorganisms, blood type, and glucose and lipid levels are also important factors in the development of pancreatic cancer. Identifying early diagnosis options is an important way to improve detection and survival rates of pancreatic cancer. None of the many tumor markers associated with pancreatic cancer are highly specific, which also indicates further research is required to improve the early detection rate. Future directions in terms of treatment evaluating the relationship between the microbiology-free system and immunotherapy will bring a major breakthrough and is expected to bring exciting clinical applications in improving the life-cycle of pancreatic cancer patients.
Understanding obesity‐related behaviors in youth from a systems dynamics perspective: The use of causal loop diagrams

This paper reports how we applied systems dynamics methods to gain insight into the complexity of obesity‐related behaviors in youth, including diet, physical activity, sedentary behavior, and sleep, by integrating a literature review into causal loop diagrams (CLDs). Results showed that the CLDs consisted of multiple subsystems and three types of dynamics appeared, including (1) feedback loops, (2) connections between feedback loops and subsystems, and (3) mechanisms. We observed clear similarities in the dynamics for the four behaviors in that they relate to “traditional” subsystems, such as home and school environments, as well as to newly added subsystems, including macroeconomics, social welfare, and urban systems. The CLDs provided insights that can support the development of intervention strategies, including (1) the confirmation that a range of mechanisms cover and connect multiple levels and settings, meaning that there is no silver bullet to address obesity; (2) understanding of how interventions in one particular setting, such as school, might be influenced by the interactions with other settings, such as urban systems; and (3) a comprehensive view of (un)intended consequences. This way of framing the problem will assist moving towards public health interventions that respond to and operate in the complexity of the real world.
Static and dynamic light-scattering solution behavior of pullulan and dextran in comparison

The conformational and dynamic behavior of fractionated samples of pullulan and dextran has been studied by means of static and dynamic light scattering. Measurements were carried out in water and in some θ solvents at various temperatures. Static light scattering yields the molar mass, M w , the radius of gyration, z 0.5 , and the second virial coefficient, A 2 . From dynamic light scattering we obtained the translational diffusion coefficient, D z,0 and the second hydrodynamic virial coefficient, k D,2
Optimization of a High Work Function Solution Processed Vanadium Oxide Hole-Extracting Layer for Small Molecule and Polymer Organic Photovoltaic Cells

We report a method of fabricating a high work function, solution processable vanadium oxide (V2Ox(sol)) hole-extracting layer. The atmospheric processing conditions of film preparation have a critical influence on the electronic structure and stoichiometry of the V2Ox(sol), with a direct impact on organic photovoltaic (OPV) cell performance. Combined Kelvin probe (KP) and ultraviolet photoemission spectroscopy (UPS) measurements reveal a high work function, n-type character for the thin films, analogous to previously reported thermally evaporated transition metal oxides. Additional states within the band gap of V2Ox(sol) are observed in the UPS spectra and are demonstrated using X-ray photoelectron spectroscopy (XPS) to be due to the substoichiometric nature of V2Ox(sol). The optimized V2Ox(sol) layer performance is compared directly to bare indium–tin oxide (ITO), poly(ethyleneoxythiophene):poly(styrenesulfonate) (PEDOT:PSS), and thermally evaporated molybdenum oxide (MoOx) interfaces in both small molec.
Predicting the response of explosives to attack by high-density shaped-charge jets

Abstract Predicting an explosive's response to jet attack would appear to be difficult due to the complex nature of the projectile. Consequently it is surprising that such a simple criterion as that obtained by Held (v2D = constant) seems to be adequate in describing the initiation boundary of a given explosive under such circumstances. This paper discusses the complexity of jet impacts and compares experimental data with initiation boundaries formed by more regular projectiles. It appears that round-nosed rods, spheres and some jets form one class of projectile while flat-nosed rods form another. Both classes of projectile obey the v2D criterion, which is shown to approximate to the critical energy criterion. Such an approximation enables predictions to be made about the effect of jet density on the initiation boundary and gives estimated values of such boundaries for explosives tested only by plate or rod impacts. Some suggestions are made as to why such simple initiation criteria work, but the nature o.
Bromocriptine for the treatment of postoperative cerebellar mutism syndrome in pediatric patients: Three case reports

Introduction Cerebellar mutism syndrome (CMS) is a common complication after posterior fossa tumor resection. It is characterized by a significant lack or loss of speech. Its biological origin remains unclear and there are no standardized treatments. However, bromocriptine seems to be a possible treatment for this condition. Case report In this paper, we present three cases of pediatric patients (4, 5, and 17-year old) who developed CMS after posterior fossa tumor surgery. They were treated with bromocriptine to improve neurological symptoms. Management and outcome: Bromocriptine was started at a low dose and was progressively increased to reach the minimum effective dose. After four months of treatment, a normal and fluid speech was observed in the three patients. No discontinuation due to adverse events were reported. Discussion Bromocriptine has shown to be an effective and safe treatment for CMS in pediatric patients after posterior fossa tumor resection.
Speaking up about patient-perceived serious visit note errors: Patient and family experiences and recommendations

BACKGROUND Open notes invite patients and families to read ambulatory visit notes through the patient portal. Little is known about the extent to which they identify and speak up about perceived errors. Understanding the barriers to speaking up can inform quality improvements. OBJECTIVE To describe patient and family attitudes, experiences, and barriers related to speaking up about perceived serious note errors. METHODS Mixed method analysis of a 2016 electronic survey of patients and families at 2 northeast US academic medical centers. Participants had active patient portal accounts and at least 1 note available in the preceding 12 months. RESULTS 6913 adult patients (response rate 28%) and 3672 pediatric families (response rate 17%) completed the survey. In total, 8724/9392 (93%) agreed that reporting mistakes improves patient safety. Among 8648 participants who read a note, 1434 (17%) perceived ≥1 mistake. 627/1434 (44%) reported the mistake was serious and 342/627 (56%) contacted their provider. Participants who self-identified as Black or African American, Asian, "other," or "multiple" race(s) (OR 0.50; 95% CI (0.26,0.97)) or those who reported poorer health (OR 0.58; 95% CI (0.37,0.90)) were each less likely to speak up than white or healthier respondents, respectively. The most common barriers to speaking up were not knowing how to report a mistake (61%) and avoiding perception as a "troublemaker" (34%). Qualitative analysis of 476 free-text suggestions revealed practical recommendations and proposed innovations for partnering with patients and families. CONCLUSIONS About half of patients and families who perceived a serious mistake in their notes reported it. Identified barriers demonstrate modifiable issues such as establishing clear mechanisms for reporting and more challenging issues such as creating a supportive culture. Respondents offered new ideas for engaging patients and families in improving note accuracy.