Miracle-dz/UniFAR-FTUs huggingface dataset:
Ultra-high frequency ultrasonography of labial glands is a highly sensitive tool for the diagnosis of Sjögren's syndrome: a preliminary study.

OBJECTIVES Ultra-high frequency ultrasonography (UHFUS) has been recently introduced in oral medicine due to its ability to image small anatomical structures including labial salivary glands (LSG). To date no ultrasonography morphological studies of labial salivary glands (LSG) have been carried out in SS. In this pilot study we aimed at analysing the distribution of UHFUS findings in LSG of patients with suspected SS, focusing in particular on the association with patients' oral dysfunction, antibody profiles and histopathology. METHODS Consecutive patients undergoing a LSG biopsy for clinically suspected SS were included in this study between January 2018 and January 2020. Intraoral UHFUS scan of the lip mucosa was performed with Vevo MD equipment, using a 70 MHz probe with a standardised protocol. LSG were assessed by using a four-grade semiquantitative scoring system (0-3), similar to the OMERACT scoring system used for major salivary glands. The distribution of UHFUS grades was compared in patients stratified according their final diagnosis, patients antibody profiles and LSG histopathology. RESULTS We included 128 patients with suspected SS: out of them, 54 (42.2%) received a final diagnosis of SS, made according to the ACR 2016 criteria and 74 (57.8%) were diagnosed as no-SS sicca controls. We found that LSG inhomogeneity was significantly greater in patients with SS than in no-SS subjects (p<0.0001). We also found that higher UHFUS pattern of inhomogeneity (i.e. grade 2 and 3) were significantly more frequent in both SSA+/SSB- and SSA+/SSB+ patients (p=0.001). A normal UHFUS pattern, by contrast, was significantly more common in SSA-/SSB- subjects (i.e. 15/83 (18.1%) vs. 1/33 (3%) vs. 0/12 (0%), p=0.001). Finally, LSG inhomogeneity was significantly associated with both the number of foci (p<0.001) and focus score (p<0.001). Particularly, we found that both the number of foci and the FS were significantly higher in patients presenting a UHFUS grading of 2 and 3 with respect to those presenting a UHFUS grading of 0 and 1 (p=0.01). CONCLUSIONS This preliminary study demonstrates the optimal feasibility of UHFUS and its high sensitivity in identifying negative patients on subsequent lip biopsy, thus avoiding invasive procedures in selected cases. Further studies are in progress to define the clinical and predictive role of the various patterns observed and their added value with respect to traditional salivary gland ultrasonography.
Artemisinin susceptibility in the malaria parasite Plasmodium falciparum: propellers, adaptor proteins and the need for cellular healing

ABSTRACT Studies of the susceptibility of Plasmodium falciparum to the artemisinin family of antimalarial drugs provide a complex picture of partial resistance (tolerance) associated with increased parasite survival in vitro and in vivo. We present an overview of the genetic loci that, in mutant form, can independently elicit parasite tolerance. These encode Kelch propeller domain protein PfK13, ubiquitin hydrolase UBP-1, actin filament-organising protein Coronin, also carrying a propeller domain, and the trafficking adaptor subunit AP-2μ. Detailed studies of these proteins and the functional basis of artemisinin tolerance in blood-stage parasites are enabling a new synthesis of our understanding to date. To guide further experimental work, we present two major conclusions. First, we propose a dual-component model of artemisinin tolerance in P. falciparum comprising suppression of artemisinin activation in early ring stage by reducing endocytic haemoglobin capture from host cytosol, coupled with enhancement of cellular healing mechanisms in surviving cells. Second, these two independent requirements limit the likelihood of development of complete artemisinin resistance by P. falciparum, favouring deployment of existing drugs in new schedules designed to exploit these biological limits, thus extending the useful life of current combination therapies.
The Role of Serotonin-cAMP Mediated Signaling in Drosophila Central Synaptic Transmission and its Implications in Larval Olfactory Associative Learning

GANGULY, ARCHAN, Ph.D., March 2012, Biological Sciences The Role of Serotonin-cAMP Mediated Signaling in Drosophila Central Synaptic Transmission and its Implications in Larval Olfactory Associative Learning Director of Dissertation: Daewoo Lee Changes in synaptic plasticity are thought to be the basis of information storage leading to memory formation. In both vertebrates and invertebrates, the cAMP signaling pathway has been shown to be critical for learning and memory. The combined use of advanced genetic tools and behavioral learning assays in Drosophila has helped define the role for cAMP signaling in olfactory associative learning. However, very little is known about how cAMP mediated changes in synaptic transmission, especially at central synapses, contribute to behavioral learning. In this thesis I have used a combination of electrophysiology on Drosophila primary neuronal cultures and behavioral larval learning assays to explore if cAMP mediated changes in synaptic plasticity can contribute to behavioral learning. I demonstrate that cAMP signaling activates PKA and thus leads to an increase in the frequency of excitatory cholinergic synaptic currents and a supression of inhibitory GABAergic synaptic currents. I also observe that cAMP modulates the inhibitory GABAergic synapses in two distinct ways. It increases pre-synaptic GABA release and also decreases post-synaptic GABAAreceptor response possibly through PKA mediated phosphorylation, thus resulting in an overall reduction of GABAergic synaptic transmission. This regulation of post-synaptic GABAA-receptors by cAMP is altered in the mushroom body (MB) neurons of cAMP 4 mutants (e.g. dunce and rutabaga). These flies have physiologically opposite levels of cAMP and show defects in olfactory learning. I further demonstrate that a biogenic amine (5-HT) increases cholinergic EPSC frequency and decreases GABAergic IPSC frequency. My work shows that 5-HT acts through the d5-HT7 receptor to activate cAMP-PKA signaling as its effect on cholinergic and GABAergic currents is similar to that observed with cAMP alone. I further note that the d5-HT7 receptor is expressed in the mushroom body neurons, which is critical for both olfactory appetitive and aversive learning. In summary, my work suggests that the d5-HT7 receptor in the MB, acting through the cAMP-PKA pathway, is as a key player in both the regulation of synaptic plasticity and olfactory associative learning in Drosophila. Approved: _____________________________________________________________ Daewoo Lee Associate Professor of Biological Sciences
Biomechanical regulation of focal adhesion and invadopodia formation

ABSTRACT Integrin adhesions are a structurally and functionally diverse family of transmembrane, multi-protein complexes that link the intracellular cytoskeleton to the extracellular matrix (ECM). The different members of this family, including focal adhesions (FAs), focal complexes, fibrillar adhesions, podosomes and invadopodia, contain many shared scaffolding and signaling ‘adhesome’ components, as well as distinct molecules that perform specific functions, unique to each adhesion form. In this Hypothesis, we address the pivotal roles of mechanical forces, generated by local actin polymerization or actomyosin-based contractility, in the formation, maturation and functionality of two members of the integrin adhesions family, namely FAs and invadopodia, which display distinct structures and functional properties. FAs are robust and stable ECM contacts, associated with contractile stress fibers, while invadopodia are invasive adhesions that degrade the underlying matrix and penetrate into it. We discuss here the mechanisms, whereby these two types of adhesion utilize a similar molecular machinery to drive very different – often opposing cellular activities, and hypothesize that early stages of FAs and invadopodia assembly use similar biomechanical principles, whereas maturation of the two structures, and their ‘adhesive’ and ‘invasive’ functionalities require distinct sources of biomechanical reinforcement. Summary: We hypothesize that similar mechanosensitive mechanisms drive focal adhesions and invadopodia initiation and maturation, despite the differences in their morphology and functions.
Patient and Physician Preferences for Antibiotics in Acute Uncomplicated Diverticulitis: A Delphi Consensus Process to Generate Noninferiority Margins

Supplemental Digital Content is available in the text. BACKGROUND: Despite the existing evidence, the omission of antibiotics in the management of acute uncomplicated diverticulitis has not gained widespread acceptance. OBJECTIVE: This study aims to incorporate the input of both patients and physicians on the omission of antibiotics in uncomplicated diverticulitis to generate noninferiority margins for 3 outcomes. DESIGN: This was a mixed-methods study, including in-person interviews with patients and a Delphi process with physicians. SETTINGS: North American patients and physicians participated. PATIENTS: Consecutive patients undergoing colonoscopy, 40% of whom had a previous history of diverticulitis, were selected. INTERVENTIONS: Informational video (for patients) and evidence summaries (for physicians) regarding antibiotics in diverticulitis were reviewed. MAIN OUTCOMES MEASURES: Noninferiority margins were generated for time to reach full recovery, persistent diverticulitis, and progression to complicated diverticulitis in the context of a nonantibiotic strategy. Consensus was defined as an interquartile range <2.5. RESULTS: Fifty patients participated in this study. To avoid antibiotics, patients were willing to accept up to 5.0 (3.0–7.0) days longer to reach full recovery, up to an absolute increase of 4.0% (4.0–6.0) in the risk of developing persistent diverticulitis, and up to an absolute increase of 2.0% (0–3.8) in the risk of progressing to complicated diverticulitis. A total of 55 physicians participated in the Delphi (round 1 response rate = 94.8%; round 2 response rate = 100%). Consensus noninferiority margins were generated for persistent diverticulitis (4.0%, 4.0–5.0) and progression to complicated diverticulitis (3.0%, 2.0–3.0), but could not be generated for time to reach full recovery (5.0 days, 3.5–7.0). LIMITATIONS: Patients were recruited from a single institution, and Delphi participants were invited and not randomly selected. CONCLUSION: Noninferiority margins were generated for 3 important outcomes after the treatment of acute uncomplicated diverticulitis in the context of a nonantibiotic strategy.
Helicobacter pylori infection and micronutrient deficiency in pregnant women: a systematic review and meta-analysis

Background Over the last few years, epidemiological studies have shown that infection with Helicobacter pylori has a major effect on micronutrient deficiency as well as on adverse pregnancy outcomes. Importantly, there are gaps in understanding the linkage of H. pylori infection with micronutrients deficiency in pregnant women. Objective We conducted a systematic review and meta-analysis to estimate the association between H. pylori infection and micronutrient deficiencies in pregnant women. Methods A systematic literature search was conducted for relevant articles using PubMed, Web of Science, and Scopus database from inception to March 2020. The OR with 95% CIs was determined by meta-analysis of data extracted from the selected studies. Results From 2384 primary articles, 6 studies were selected for systematic reviews and 4 studies distinctively (with 1274 participants: 553 cases and 721 controls) were selected for meta-analysis. The meta-analysed fixed effect model estimated the odds of having H. pylori infection was not significantly higher among pregnant women with micronutrient deficiencies than those without deficiencies (OR=1.12, 95% CI 0.88 to 1.42, p=0.37). In the subgroup analysis, no correlation was found between H. pylori infection and vitamin B12 (OR=0.74, 95% CI 0.45 to 1.21, p=0.22), folate (OR=1.07, 95% CI 0.73 to 1.58, p=0.73), and ferritin (OR=0.81, 95% CI 0.51 to 1.31, p=0.4). However, a positive correlation was found between iron-deficiency anaemia (IDA) and H. pylori infection (OR=16.23, 95% CI 4.19 to 62.93, p<0.0001) during pregnancy. Conclusion H. pylori infection is associated with increased risk of IDA but not with deficiency of other micronutrients in pregnancy. PROSPERO registration number CRD42019135683.
Effects of biochar application on nitrogen leaching, ammonia volatilization and nitrogen use efficiency in two distinct soils

This study was conducted to determine the effect of biochar application on nitrogen (N) leaching, ammonia (NH3) volatilization, and fertilizer N use efficiency (NUE) in two soils with different properties (loamy and sandy). Ryegrass (Lolium perenne L.) incubation experiments (with 15N-enriched urea applied) and an N loss simulation study were conducted at biochar application rates of 2% and 4%. The results showed that 15N utilization increased by 8.83–9.06% following the addition of biochar to sandy soil during the first season compared with the control. However, this significant effect was not observed in the loamy soil, in which significantly more urea-N was retained in the soil following biochar application. Furthermore, based on the results of the N leaching and NH3 volatilization experiments, 29.19% and 28.65% NO3-N leaching reductions were induced by 2% and 4% biochar amendments in loamy soil, decreasing the total inorganic N that was leached (NH4+-N plus NO3-N) by 26.46% and 26.82%, respectively. However, although the amount of leached NH4+-N decreased in biochar-amended sandy soil, the cumulative NH3 volatilizations were 14.18–20.05% higher than in the control, and 22.55% more NO3--N was leached from biochar-amended sandy soil, resulting in a negative effect on N retention. According to this study, biochar can be effectively used to improve the NUE in sandy soil and reduce N loss from loamy soil.
Exploring the copper binding ability of Mets7 hCtr‐1 protein domain and His7 derivative: An insight in Michael addition catalysis

Mets7 is a methionine‐rich motif present in hCtr‐1 transporter that is involved in copper cellular trafficking. Its ability to bind Cu(I) was recently exploited to develop metallopeptide catalysts for Henry condensation. Here, the catalytic activity of Mets7‐Cu(I) complex in Michael addition reactions has been evaluated. Furthermore, His7 peptide, in which Met residues have been substituted with His ones, was also prepared. This substitution allowed His7 to coordinate Cu (II), with the obtainment of a stable turn conformation as evicted by CD experiments. His7‐Cu (II) proved also to be a better catalyst than Mets7‐Cu(I) in the addition reaction. In particular, when the substrate was the (E)‐1‐phenyl‐3‐(pyridin‐2‐yl)prop‐2‐en‐1‐one, a conversion of 71% and a significative 58% of e.e. was observed.
Antibody kinetics and serologic profiles of SARS-CoV-2 infection using two serologic assays

Background Coronavirus disease 2019 (COVID-19) is an emerging threat worldwide. This study aims to assess the serologic profiles and time kinetics of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with COVID-19 using two immunoassays. Methods A total of 97 samples serially collected from 17 patients with COVID-19 and 137 negative control samples were analyzed for IgM and IgG against SARS-CoV-2 using the AFIAS COVID-19 Ab (Boditech Med Inc., Chuncheon, Republic of Korea) and the EDI™ Novel Coronavirus COVID-19 ELISA Kit (Epitope Diagnostics, Inc., San Diego, CA). Results With both assays, IgM and IgG rapidly increased after 7 days post symptom onset (PSO). IgM antibody levels reached a peak at 15–35 d PSO and gradually decreased. IgG levels gradually increased and remained at similar levels after 22–35 d. The diagnostic sensitivities of IgM/IgG for ≤14d PSO were 21.4%/35.7~57.1% and increased to 41.2~52.9%/88.2~94.1% at >14 d PSO with specificities of 98.5%/94.2% for AFIAS COVID-19 Ab and 100.0%/96.4% for EDI™ Novel Coronavirus COVID-19 ELISA Kit. Among 137 negative controls, 12 samples (8.8%) showed positive or indeterminate results. Conclusions The antibody kinetics against SARS-CoV-2 are similar to common findings of acute viral infectious diseases. Antibody testing is useful for ruling out SARS-CoV-2 infection after 14 d PSO, detecting past infection, and epidemiologic surveys.
Urban vs. Rural Socioeconomic Differences in the Nutritional Quality of Household Packaged Food Purchases by Store Type

The U.S. food system is rapidly changing, including the growth of mass merchandisers and dollar stores, which may impact the quality of packaged food purchases (PFPs). Furthermore, diet-related disparities exist by socioeconomic status (SES) and rural residence. We use data from the 2010–2018 Nielsen Homescan Panel to describe the nutritional profiles of PFPs by store type and to assess whether these vary by household urbanicity and SES. Store types include grocery stores, mass merchandisers, club stores, online shopping, dollar stores, and convenience/drug stores. Food and beverage groups contributing the most calories at each store type are estimated using survey-weighted means, while the associations of urbanicity and SES with nutritional quality are estimated using multivariate regression. We find that households that are customers at particular store types purchase the same quality of food regardless of urbanicity or SES. However, we find differences in the quality of foods between store types and that the quantity of calories purchased at each store type varies according to household urbanicity and SES. Rural shoppers tend to shop more at mass merchandisers and dollar stores with less healthful PFPs. We discuss implications for the types of store interventions most relevant for improving the quality of PFPs.
Cumulative Occupational Exposures and Lung Function Decline in Two Large General Population Cohorts.

RATIONALE Few longitudinal studies have assessed the relationship between occupational exposures and lung function decline in the general population, with sufficiently long follow-up. OBJECTIVES Our objective was to examine this potential association in two large cohorts (ECRHS and SAPALDIA). METHODS General population samples aged 18 to 62 were randomly selected in 1991-1993, and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a Job-Exposure Matrix, generating cumulative exposure estimates for 12 occupational exposures. FEV1 and FVC were jointly modelled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking. RESULTS A total of 40,024 lung function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV1 and the FEV1/FVC ratio for exposure to biological dust, mineral dust and metals (FEV1 -15.1ml, -14.4ml and -18.7ml respectively, and FEV1/FVC -0.52%, -0.43% and -0.36% respectively, per 25 intensity-years of exposure). These declines were comparable in magnitude to those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and SAPALDIA cohorts. CONCLUSIONS Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung function decline. This highlights the need to prevent or control these exposures in the workplace.
Significance of anti-La/SSB antibodies in primary Sjögren's syndrome patients with combined positivity for anti-Ro/SSA and salivary gland biopsy.

OBJECTIVES Immunological parameters exert a relevant diagnostic and prognostic role in primary Sjögren's syndrome (pSS) and may identify specific disease phenotypes. Among disease-associated immunological features, anti-La/SSB are rarely found without concomitant anti-Ro/SSA and their clinical significance in patients with pSS has been poorly investigated. Thus, we aimed to characterise the value of anti-La/SSB analysing clinical and serologic features of a wide cohort of pSS patients with both circulating anti-Ro/SSA and positive salivary gland biopsy (SGB). METHODS Clinical and serological data of 600 pSS patients with both anti-Ro/SSA and SGB positivity and categorised according to anti-La/SSB status were retrospectively analysed. Comparisons between patients with and without circulating anti-La/SSB were performed. RESULTS Among the whole cohort, 319 (53%) of patients were anti-La/SSB negative and 281 (47%) were anti-La/SSB positive. Anti-La/SSB positive patients were younger at disease diagnosis and had a longer disease duration. Moreover, anti-La/SSB positive patients had a higher prevalence of hypergammaglobulinaemia and circulating rheumatoid factor and of lymphoproliferative disorders in comparison to seronegative group. At multivariate analysis, hypergammaglobulinaemia (OR=1,7; 95% CI 1.17, 2.43), rheumatoid factor (OR=2.3; 95% CI 1.6, 3.3) and lymphoma (OR=2.6; 95% CI 1.12, 5.96) were identified as independent variables significantly associated with anti-La/SSB positivity. CONCLUSIONS In patients with pSS and concomitant anti-Ro/SSA and SGB positivity, the presence of anti-La/SSB may help in identifying a disease subset with distinct prognostic features, especially in terms of higher risk of lymphoproliferative complications.
Taxonomic status and phylogenetic relationships of Boulengerula denhardtiNieden, 1912 (Amphibia, Gymnophiona, Caeciliidae)

The Kenyan caeciliid caecilian Boulengerula denhardtiNieden 1912 was considered to be a junior synonym of Schistometopum (Dermophis) gregorii (Boulenger, 1894) by Loveridge (1936). This synonymy has been accepted, implicitly or explicitly, by all subsequent workers. Re-examination of the holotype and only known specimen of B. denhardti confirmed Nieden's (1912) assessment that this form represents a distinctive species of Boulengerula. We resurrect B. denhardti from the synonymy of Schistometopum gregorii, rediagnose the species, redescribe the holotype, and provide an updated key to the species of Boulengerula. The phylogenetic relationships of the species of Boulengerula are examined on the basis of morphological data. It is concluded that the available morphological data are insufficient to resolve relationships with any confidence at this time. The caecilian fauna of the Tana River region is briefly discussed. Boulengerula denhardti (Gymnophiona: Caeciliidae) wurde von Nieden (1912) anhand eines einzigen Exemplars aus dem Gebiet des Tana Flusses im sudostlichen Kenia beschrieben. Im Zuge seiner eigenen Untersuchungen zur Gymnophionenfauna des Tana-Deltas uberfuhrte Loveridge (1936) B. denhardtii in die Synonymie von Schistometopum gregorii. Diese Synonymisierung erfolgte offensichtlich aufgrund einer Fehlinterpretation der publizierten Beschreibung. Unsere Untersuchung des Holotypus von B. denhardti zeigt, dass es sich hierbei um eine distinkte, valide Art handelt, welche wir hier neu beschreiben und neu diagnostizieren. Ein neuer Bestimmungsschlussel fur alle bekannten Arten von Boulengerula wird ebenfalls vorgestellt. Die Verwandtschaftsbeziehungen der einzelnen Boulengerula-Arten werden neu untersucht, wobei gezeigt wird, dass die bekannten morphologischen Merkmale zu deren Auflosung nicht ausreichen. Die Gymnophionenfauna des Tanagebietes wird kurz diskutiert.