Miracle-dz/UniFAR-FTUs huggingface dataset:
Transmission of tuberculosis between foreign-born and Finnish-born populations in Finland, 2014–2017

We describe the epidemiology of tuberculosis (TB) and characterized Mycobacterium tuberculosis (M. tuberculosis) isolates to evaluate transmission between foreign-born and Finnish-born populations. Data on TB cases were obtained from the National Infectious Disease Register and denominator data on legal residents and their country of birth from the Population Information System. M. tuberculosis isolates were genotyped by spoligotyping and Mycobacterial Interspersed Repetitive Unit Variable Number Tandem Repeat (MIRU-VNTR). We characterized clusters by age, sex, origin and region of living which included both foreign-born cases and those born in Finland. During 2014–2017, 1015 TB cases were notified; 814 were confirmed by culture. The proportion of foreign-born cases increased from 33.3% to 39.0%. Foreign-born TB cases were younger (median age, 28 vs. 75 years), and had extrapulmonary TB or multidrug-TB more often than Finnish-born cases (P<0.01 for all comparisons). Foreign-born cases were born in 60 different countries; most commonly in Somalia (25.5%). Altogether 795 isolates were genotyped; 31.2% belonged to 80 different clusters (range, 2–13 cases/cluster). Fourteen (17.5%) clusters included isolates from both Finnish-born and foreign-born cases. An epidemiological link between cases was identified by (epidemiological) background information in two clusters. Although the proportion of foreign-born TB cases was considerable, our data suggests that transmission of TB between foreign and Finnish born population is uncommon.
Survival analysis of patients with tuberculosis and risk factors for multidrug-resistant tuberculosis in Monrovia, Liberia

We reviewed the records of 337 confirmed cases of tuberculosis patients in Monrovia, the capital of Liberia, 2015. The risk factors affecting the survival and multidrug-resistance of tuberculosis patients were examined. Kaplan-Meier analysis and the log-rank test were used to assess the differences in survival among the patients, while Cox regression model was used for multivariate analysis. The qualitative data was tested with chi-square test in the single factor analysis of multidrug-resistant TB. Multivariate analysis was performed using binary logistic regression analysis. The significance level for all the tests were set at 0.05. The mean period of the follow-up of patients was 10 months. In the 337 patients, 33 (9.8%) died, the 21-month survival rate was 90.2%. The results of multivariate Cox regression analysis show that overcrowding (HR = 7.942, 95% CI 3.258–19.356), former smoking (HR = 3.773, 95% CI 1.601–8.889), current smoking (HR = 3.546, 95% CI 1.195–10.521), multidrug-resistance tuberculosis (HR = 4.632, 95% CI 1.913–11.217) were risk factors for death during anti-tuberculosis treatment in TB patients in Liberia. The results of binary logistic regression analysis show that extra-pulmonary (OR = 2.032, 95% CI 1.133–3.644), family history of TB (OR = 2.387, 95% CI 1.186–4.807) and current smoking (OR = 3.436, 95% CI 1.681–7.027) were risk factors for multidrug-resistant tuberculosis. These results can provide insights on local tuberculosis early intervention, increase public health awareness, and strengthen the control of factors that may affect the survival and multidrug-resistance of tuberculosis patients.
PMN-derived netrin-1 attenuates cardiac ischemia-reperfusion injury via myeloid ADORA2B signaling

Myocardial ischemia-reperfusion injury generates sterile inflammation sites in which neutrophils are activated and cause myocardial reperfusion injury. During this event, the neuronal guidance molecule netrin-1 is released by activated neutrophils and dampens myocardial inflammation by activating adenosine receptors (ADORA2B) expressed on myeloid immune cells.
Bilateral osteochondral defects of the patellae in an 11-year-old girl

Osteochondral defect or osteochondritis dissecans (OCD) of the knee usually affects young, active populations. It is a challenging diagnosis as patients typically present with poorly localised activity-related pain, which is non-specific and covers many differentials. We present an active 11-year-old girl with bilateral osteochondral defects of the patellae: a rare clinical disorder which was affecting her sporting activities. She had a 12-month history of bilateral anterior knee pain before the diagnosis was achieved with appropriate imaging. Her pain significantly improved with activity modification and physiotherapy. Follow-up will require outpatient clinic assessment and imaging to determine if non-operative management continues to be successful or surgery may be required. This case report emphasises the importance of appropriate high index of suspicion when managing patients with non-specific knee pain. It also demonstrates the importance of judicious use of imaging to avoid a missed or delayed diagnosis.
Hydraulic resistance induces cell phenotypic transition in confinement

Hydraulic resistance induces cell phenotype oscillations in confinement via the coupled dynamics of actin, myosin, and calcium. Cells penetrating into confinement undergo mesenchymal-to-amoeboid transition. The topographical features of the microenvironment expose cells to different hydraulic resistance levels. How cells respond to hydraulic resistance is unknown. We show that the cell phenotype shifts from amoeboid to mesenchymal upon increasing resistance. By combining automated morphological tracking and wavelet analysis along with fluorescence recovery after photobleaching (FRAP), we found an oscillatory phenotypic transition that cycles from blebbing to short, medium, and long actin network formation, and back to blebbing. Elevated hydraulic resistance promotes focal adhesion maturation and long actin filaments, thereby reducing the period required for amoeboid-to-mesenchymal transition. The period becomes independent of resistance upon blocking the mechanosensor TRPM7. Mathematical modeling links intracellular calcium oscillations with actomyosin turnover and force generation and recapitulates experimental data. We identify hydraulic resistance as a critical physical cue controlling cell phenotype and present an approach for connecting fluorescent signal fluctuations to morphological oscillations.
Onychomycosis and Tinea Pedis in the Feet of Patients With Diabetes

This study aimed to determine the prevalence of onychomycosis and interdigital tinea pedis in a cohort of Spanish patients with diabetes in whom onychomycosis was clinically suspected (n = 101). Samples from a first toenail scraping and the fourth toe clefts were subjected to potassium hydroxide direct vision and incubated in Sabouraud and dermatophyte test medium. Fifty-eight samples were also analyzed by a pathologist using periodic acid-Schiff staining and Calcofluor white direct fluorescence microscopy. Onychomycosis was only confirmed in 41 patients (40.6%). The most frequent aetiological agent was Trichophyton rubrum, isolated in 10 patients (36%), followed by Candida parapsilosis in 7 patients (25%). Tests on the fourth toe cleft samples were only positive in 11 patients (10.9%), and in all cases, onychomycosis was also diagnosed. Neuroischemic foot was the only significant variable associated with onychomycosis in the univariate analysis (P < .01). A positive result for mycosis in the fourth toe cleft was found in 11 cases (10.9%) and was associated with a history of myocardial infarction (P< .01; odds ratio [OR]: 84.2, confidence interval [CI]: 6.8-1036.4) and neuroischemic foot (P< .01; OR: 13.7, CI: 12.6-71.6) in the multivariate model. In conclusion, the prevalence of onychomycosis and tinea pedis in patients with diabetes in whom onychomycosis was clinically suspected was 40.6% and 10.9%, respectively. In addition, onychomycosis was not always associated with tinea pedis. These results show that clinical diagnosis has low accuracy in people with diabetes mellitus, and that diagnosis should not be based on clinical toenail characteristics alone.
Differential abnormalities of cerebrospinal fluid dopaminergic versus noradrenergic indices in synucleinopathies

The synucleinopathies Parkinson's disease (PD), multiple system atrophy (MSA), and pure autonomic failure (PAF) are characterized by intra‐cytoplasmic deposition of the protein alpha‐synuclein and by catecholamine depletion. PAF, which manifests with neurogenic orthostatic hypotension (nOH) and no motor signs of central neurodegeneration, can evolve into PD+nOH. The cerebrospinal fluid (CSF) levels of catecholamine metabolites may indicate central catecholamine deficiency in these synucleinopathies, but the literature is inconsistent and incomplete. In this retrospective cohort study we reviewed data about CSF catecholamines, the dopamine metabolites 3,4‐dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the norepinephrine metabolites 3,4‐dihydroxyphenylglycol (DHPG) and 3‐methoxy‐4‐hydroxyphenylglycol (MHPG). The compounds were measured in 36 patients with PD, 37 patients with MSA, and 19 patients with PAF and in 38 controls. Compared to the control group, the PD, MSA, and PAF groups had decreased CSF MHPG (p < .0001 each by Dunnett's post hoc test), DHPG (p = .004; p < .0001; p < .0001) and norepinephrine (p = .017; p = .0003; p = .044). CSF HVA and DOPAC were decreased in PD (p < .0001 each) and MSA (p < .0001 each) but not in PAF. The three synucleinopathies therefore have in common in vivo evidence of central noradrenergic deficiency but differ in the extents of central dopaminergic deficiency—prominent in PD and MSA, less apparent in PAF. Data from putamen 18F‐DOPA and cardiac 18F‐dopamine neuroimaging in the same patients, post‐mortem tissue catecholamines in largely separate cohorts, and review of the neuropathology literature fit with these distinctions. The results suggest a ‘norepinephrine first’ ascending pathogenetic sequence in synucleinopathies, with degeneration of pontine locus ceruleus noradrenergic neurons preceding the loss of midbrain substantia nigra dopaminergic neurons.
Predicted climate‐induced reductions in scavenging in eastern North America

Scavenging is an important function within ecosystems where scavengers remove organic matter, reduce disease, stabilize food webs, and generally make ecosystems more resilient to environmental changes. Global change (i.e., changing climate and increasing human impact) is currently influencing scavenger communities. Thus, understanding what promotes species richness in scavenger communities can help prioritize management actions. Using a long‐term dataset from camera traps deployed with animal carcasses as bait along a 1881 km latitudinal gradient in the Appalachian Mountains of eastern USA, we investigated the relative impact of climate and humans on the species richness and diversity of vertebrate scavengers. Our most supported models for both mammalian and avian scavengers included climatic, but not human, variables. The richness of mammalian and avian scavengers detected was highest during relatively warm (5–10°C) and dry (100–150 mm precipitation) winters, when food was likely limited and both reliance on and detection of carrion was high. The diversity of mammalian and avian scavengers detected was highest under drier conditions. We then used these results to project the future species richness of scavengers that would be detected within our sampling area and under the climate scenario of 2070 (emissions level RCP8.5). Our predictions suggest up to 80% and 67% reductions, respectively, in the richness of avian and mammalian scavengers that would be detected at baited sites. Climate‐induced shifts in behavior (i.e., reduction in scavenging, even if present) at this scale could have cascading implications for ecosystem function, resilience, and human health. Further, our study highlights the importance of conducting studies of scavenger community dynamics within ecosystems across wide spatial gradients within temperate environments. More broadly, these findings build upon our understanding of the impacts of climate‐induced adjustments in behavior that can likely have negative impacts on systems at a large scale.
Integrated genomic analysis identifies driver genes and cisplatin-resistant progenitor phenotype in pediatric liver cancer.

Pediatric liver cancers (PLCs) comprise diverse diseases affecting infants, children and adolescents. Despite overall good prognosis, PLCs display heterogeneous response to chemotherapy. Integrated genomic analysis of 126 pediatric liver tumors showed a continuum of driver mechanisms associated with patient age, including new targetable oncogenes. In 10% of hepatoblastoma patients, all before 3 years old, we identified a mosaic premalignant clonal expansion of cells altered at the 11p15.5 locus. Analysis of spatial and longitudinal heterogeneity revealed an important plasticity between 'Hepatocytic', 'Liver Progenitor' and 'Mesenchymal' molecular subgroups of hepatoblastoma. We showed that during chemotherapy, 'Liver Progenitor' cells accumulated massive loads of cisplatin-induced mutations with a specific mutational signature, leading to the development of heavily mutated relapses and metastases. Drug screening in PLC cell lines identified promising targets for cisplatin-resistant progenitor cells, validated in mouse xenograft experiments. These data provide new insights into cisplatin resistance mechanisms in PLC and suggest alternative therapies.
Caries Preventive and Antibacterial Effects of Two Natural Mouthwashes vs Chlorhexidine in High Caries-risk Patients: A Randomized Clinical Trial.

AIM AND OBJECTIVE To evaluate the caries preventive and antibacterial effects of Gum Arabic and Licorice mouthwashes vs chlorhexidine in high caries-risk patients. The prevalence of oral side effects from using the mouthwashes was also assessed. MATERIALS AND METHODS Total 63 participants categorized as high caries-risk according to the CAMBRA caries-risk model were recruited. They were randomly allocated to three groups (n = 21) according to the mouthwash used: G1 (Gum Arabic), G2 (Licorice), and G3 (Chlorhexidine). Baseline DMF scores and saliva samples were obtained. DMF scores, salivary Streptococcus mutans (SM) and Lactobacillus acidophilus (LA) counts, and any reported oral side effects were recorded after 3, 6, 9, and 12 months. The obtained results were subjected to the statistical analysis and the significance level was set at p ≤ 0.05. RESULTS Regarding DMF scores, no statistically significant difference was found between the three groups at baseline, after 3, 6, and 9 months. After 12 months, a statistically significant difference was found between G3 and each of G1 and G2 where G3 showed significantly higher DMF scores (p < 0.001). No statistically significant difference was found between G1 and G2. Regarding antibacterial activity, after 6 months, all mouthwashes showed statistically significant antibacterial effect against SM and LA with no statistically significant difference between them (p < 0.001). After 9 and 12 months, G1 and G2 showed a statistically significant reduction in SM and LA counts (p < 0.001). However, G3 showed a statistically significant increase in SM and LA counts indicating bacterial resistance (p < 0.001). No oral side effects were reported in G1 and G2. On the other hand, several oral side effects were reported in G3. CONCLUSION Gum Arabic and Licorice mouthwashes show promising caries preventive and antibacterial effects with no oral side effects reported. CLINICAL SIGNIFICANCE Natural mouthwashes can serve as substitutes to chemical agents as chlorhexidine, providing effective caries control and safe long-term use.
First Dose of BNT162b2 mRNA Vaccine in a Healthcare Worker Cohort Is Associated With Reduced Symptomatic and Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection

Abstract Over the first 2 months of 2021, vaccination coverage of staff at Hull Teaching Hospitals with BNT162b2 increased from 8.3% to 82.5% and was associated with a significant reduction in symptomatic and asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases. The proportion of positive lateral flow tests from asymptomatic screening was maintained over this period.
Evaluation of left ventricular systolic synchrony by peak strain dispersion in patients with rheumatoid arthritis

Objective To investigate the clinical value of the peak strain dispersion (PSD) in evaluating left ventricular (LV) systolic synchrony in patients with rheumatoid arthritis (RA). Methods One hundred eleven patients with RA were divided into two groups according to their disease duration: <5 years (Group I, n = 60) and ≥5 years (Group II, n = 51). The control group comprised 57 healthy subjects without RA. All three groups were examined by transthoracic two-dimensional echocardiography. Traditional parameters were measured by conventional echocardiography. Two-dimensional speckle tracking imaging was used to analyze the PSD and LV global longitudinal strain (LVGLS). Related ultrasound and blood test results were analyzed and compared. Results The PSD gradually increased in the order of the control group, Group I, and Group II, and the difference among the groups was statistically significant. The LVGLS gradually decreased in the order of the control group, Group I, and Group II, and the difference among the groups was statistically significant. The PSD was negatively correlated with the LVGLS. Conclusions LV systolic synchrony in patients with RA gradually decreases as the disease course progresses. The PSD can be used as a new reliable index to evaluate LV systolic synchrony.
Hyperexcitability and Loss of Feedforward Inhibition Contribute to Aberrant Plasticity in the Fmr1KO Amygdala

Abstract Fragile X syndrome (FXS) is a neurodevelopmental disorder (NDD) characterized by intellectual disability, autism spectrum disorders (ASDs), and anxiety disorders. The disruption in the function of the FMR1 gene results in a range of alterations in cellular and synaptic function. Previous studies have identified dynamic alterations in inhibitory neurotransmission in early postnatal development in the amygdala of the mouse model of FXS. However, little is known about how these changes alter microcircuit development and plasticity in the lateral amygdala (LA). Using whole-cell patch clamp electrophysiology, we demonstrate that principal neurons (PNs) in the LA exhibit hyperexcitability with a concomitant increase in the synaptic strength of excitatory synapses in the BLA. Further, reduced feed-forward inhibition appears to enhance synaptic plasticity in the FXS amygdala. These results demonstrate that plasticity is enhanced in the amygdala of the juvenile Fmr1 knock-out (KO) mouse and that E/I imbalance may underpin anxiety disorders commonly seen in FXS and ASDs.
Correlates of Neutralization against SARS-CoV-2 Variants of Concern by Early Pandemic Sera

Widespread immunity to SARS-CoV-2 will be necessary to end the COVID-19 pandemic. NAb responses are a critical component of immunity that can be stimulated by natural infection as well as vaccines. ABSTRACT Emerging SARS-CoV-2 variants of concern that overcome natural and vaccine-induced immunity threaten to exacerbate the COVID-19 pandemic. Increasing evidence suggests that neutralizing antibody (NAb) responses are a primary mechanism of protection against infection. However, little is known about the extent and mechanisms by which natural immunity acquired during the early COVID-19 pandemic confers cross-neutralization of emerging variants. In this study, we investigated cross-neutralization of the B.1. 1.7 and B.1. 351 SARS-CoV-2 variants in a well-characterized cohort of early pandemic convalescent subjects. We observed modestly decreased cross-neutralization of B.1. 1.7 but a substantial 4.8-fold reduction in cross-neutralization of B.1. 351. Correlates of cross-neutralization included receptor binding domain (RBD) and N-terminal domain (NTD) binding antibodies, homologous NAb titers, and membrane-directed T cell responses. These data shed light on the cross-neutralization of emerging variants by early pandemic convalescent immune responses. IMPORTANCE Widespread immunity to SARS-CoV-2 will be necessary to end the COVID-19 pandemic. NAb responses are a critical component of immunity that can be stimulated by natural infection as well as vaccines. However, SARS-CoV-2 variants are emerging that contain mutations in the spike gene that promote evasion from NAb responses. These variants may therefore delay control of the COVID-19 pandemic. We studied whether NAb responses from early COVID-19 convalescent patients are effective against the two SARS-CoV-2 variants, B.1. 1.7 and B.1. 351. We observed that the B.1. 351 variant demonstrates significantly reduced susceptibility to early pandemic NAb responses. We additionally characterized virological, immunological, and clinical features that correlate with cross-neutralization. These studies increase our understanding of emerging SARS-CoV-2 variants.
Copper mining bacteria: Converting toxic copper ions into a stable single-atom copper

Single-atom zero-valent copper was biosynthesized by a copper-resistant bacterium isolated from a copper mine in Brazil. The chemical synthesis of monoatomic metallic copper is unfavorable and requires inert or reductive conditions and the use of toxic reagents. Here, we report the environmental extraction and conversion of CuSO4 ions into single-atom zero-valent copper (Cu0) by a copper-resistant bacterium isolated from a copper mine in Brazil. Furthermore, the biosynthetic mechanism of Cu0 production is proposed via proteomics analysis. This microbial conversion is carried out naturally under aerobic conditions eliminating toxic solvents. One of the most advanced commercially available transmission electron microscopy systems on the market (NeoArm) was used to demonstrate the abundant intracellular synthesis of single-atom zero-valent copper by this bacterium. This finding shows that microbes in acid mine drainages can naturally extract metal ions, such as copper, and transform them into a valuable commodity.
Clinical significance of quantitative e antigen in a cohort of hepatitis B virus‐infected children and adults in North America

Background: In chronic hepatitis B (CHB) viral infection, e antigen positivity (HBeAg+) is associated with high levels of viral replication and infectivity. Furthermore, HBeAg‐positive CHB is associated with a liver disease spectrum ranging from none to severe. Aim: To assess whether the level of circulating HBeAg is associated with different clinical presentations of HBeAg‐positive CHB. Methods: A cross‐sectional analysis was conducted among HBV mono‐infected participants enrolled in Hepatitis B Research Network (HBRN) cohorts to explore clinical and virological associations with quantitative HBeAg (qHBeAg). Results: Among 763 HBeAg+ participants (56% female; 85% Asian; median age 26 years), multivariable median regression modelling significantly associated qHBeAg with liver injury (inverse qHBeAg association with ALT p<.001 and APRI p<.001), and with both race and age (p=0.01). Among Asians, qHBeAg was inversely related to age; a relationship less clear among Blacks and Whites. Among Asians also, median qHBeAg levels were higher among those infected with HBV genotype C versus B (p<0.001), suggesting causal virologic differences. Across all races, median qHBeAg was higher in women (p=.01). Independent of sex, age, race and HBV genotype, qHBeAg was higher in participants with predominant wild‐type versus basal core promoter and/or precore ‘stop’ viral variants (p<0.001). Conclusion: Lower qHBeAg was observed among HBRN participants with the greatest degree of liver injury independent of demographics and HBV genotype. These data support longitudinal studies to examine the role of qHBeAg in modulating the host immune response and predicting the outcomes of chronic HBV infection.