Miracle-dz/UniFAR-FTUs huggingface dataset:
The (in)complete organelle genome: exploring the use and nonuse of available technologies for characterizing mitochondrial and plastid chromosomes

Not long ago, scientists paid dearly in time, money and skill for every nucleotide that they sequenced. Today, DNA sequencing technologies epitomize the slogan ‘faster, easier, cheaper and more’, and in many ways, sequencing an entire genome has become routine, even for the smallest laboratory groups. This is especially true for mitochondrial and plastid genomes. Given their relatively small sizes and high copy numbers per cell, organelle DNAs are currently among the most highly sequenced kind of chromosome. But accurately characterizing an organelle genome and the information it encodes can require much more than DNA sequencing and bioinformatics analyses. Organelle genomes can be surprisingly complex and can exhibit convoluted and unconventional modes of gene expression. Unravelling this complexity can demand a wide assortment of experiments, from pulsed‐field gel electrophoresis to Southern and Northern blots to RNA analyses. Here, we show that it is exactly these types of ‘complementary’ analyses that are often lacking from contemporary organelle genome papers, particularly short ‘genome announcement’ articles. Consequently, crucial and interesting features of organelle chromosomes are going undescribed, which could ultimately lead to a poor understanding and even a misrepresentation of these genomes and the genes they express. High‐throughput sequencing and bioinformatics have made it easy to sequence and assemble entire chromosomes, but they should not be used as a substitute for or at the expense of other types of genomic characterization methods.
JC virus infects the enteric glia of patients with chronic idiopathic intestinal pseudo-obstruction

Background and aim: Chronic idiopathic intestinal pseudo-obstruction (CIIP) is characterised by severe impairment of intestinal propulsive motility that mimics bowel obstruction. JC virus (JCV) is a polyomavirus that can infect brain glial cells causing a fatal disease, but may also be found throughout the normal gastrointestinal tract. The hypothesis that JCV infects the myenteric plexuses of patients with CIIP was tested. Methods: 10 patients with CIIP and 61 normal specimens (30 ascending colon and 31 ileum) from patients with uncomplicated colon cancer were studied. DNA was extracted from the myenteric plexuses, and JCV T antigen (TAg) DNA and the viral regulatory region were detected by PCR and sequencing. Immunohistochemistry was performed to detect JCV viral protein expression, neuronal and glial markers. Fluorescence in situ hybridisation was performed for cellular localisation of the JCV infection. Results: Clinical studies demonstrated neurogenic impairment, and pathological analyses showed neuropathy in each patient with CIIP. JCV TAg DNA was found in the myenteric plexuses of 8/10 (80%) of the patients with CIIP and 3/31 (9.7%) of the control patients (p<0.001). All samples were JCV Mad-1 strains. Seven of the 10 CIIP specimens expressed both JCV TAg and the JCV viral protein VP1, while none of the controls expressed either. JCV infection co-localised with glial fibrillary acidic protein expression, a marker of enteric glial cells. Conclusion: JCV infection occurs in the myenteric plexuses of patients with CIIP. The JCV localisation in enteroglial cells suggests a possible pathological role for this virus in enteric neuropathy.
Characterizing Blood Pressure, Heart Rate, Physical Activity, Circadian Rhythm and their Response to NOS Inhibitor and Substrate in CHF Rats with Telemetry

The radio-telemetric technology makes it possible to continuously monitor arterial pressure, heart rate and physical activity as well as their circadian rhythms and their response to therapeutics in unrestrained animals for a longer period of time. This is essential for in vivo cardiovascular research. The primary purpose of the present study was to use telemetry to characterize those physiological parameters in a rat model of heart failure post myocardial infarction. Moreover, some of the neurohormonal alterations and the hemodynamic responses to L-arginine, the substrate for nitric oxide synthase (NOS), and L-NAME that inhibits NOS activity were also evaluated. Rats with moderate and large myocardial infarction are considered to have chronic heart failure (CHF), which displayed decreased systolic and consequently decreased mean blood pressure, blunted diurnal dips in systolic, diastolic and mean blood pressure, narrowed pulse pressure and relatively reduced strength of physical activity. These telemetric alterations were accompanied by increased left ventricular end diastolic pressure, right and left ventricular hypertrophy and elevated plasma norepinephrine and tumor necrosis factor. In CHF rats, L-arginine widened pulse pressure and L-NAME caused attenuated pressor response, suggesting the presence of the general NO deficiency in this model. Thus, telemetry provides some new and unique information about CHF in rats, which is important in exploring the underlying mechanism of heart failure, but cannot be obtained by the conventional approach.
Diagnosing vulnerability and “dangerousness”: police use of Section 136 in England and Wales

Purpose – Police in England and Wales are empowered, under Section 136 of the Mental Health Act 1983 (s136), to detain individuals thought to be a danger to themselves or to others. Use of this authority is widespread, but varies across districts and attracts controversy because of inconsistent application and the fact that it requires police to make judgements about mental health. The purpose of this paper is to examine police attitudes to and criteria for using s136. Design/methodology/approach – The authors conducted focus groups with 30 officers in urban and rural areas of three different regions across England and Wales. Group interviews were audio-recorded, transcribed, and analysed using open and axial coding. Findings – Use of s136 authority has major implications for police work; liaison with mental health services is seen as desirable but often ineffective due to resource constraints and the latter's lack of availability. The decision to invoke s136 depends on social context and other particular.
Taxonomy‐free molecular diatom index for high‐throughput eDNA biomonitoring

Current biodiversity assessment and biomonitoring are largely based on the morphological identification of selected bioindicator taxa. Recently, several attempts have been made to use eDNA metabarcoding as an alternative tool. However, until now, most applied metabarcoding studies have been based on the taxonomic assignment of sequences that provides reference to morphospecies ecology. Usually, only a small portion of metabarcoding data can be used due to a limited reference database and a lack of phylogenetic resolution. Here, we investigate the possibility to overcome these limitations using a taxonomy‐free approach that allows the computing of a molecular index directly from eDNA data without any reference to morphotaxonomy. As a case study, we use the benthic diatoms index, commonly used for monitoring the biological quality of rivers and streams. We analysed 87 epilithic samples from Swiss rivers, the ecological status of which was established based on the microscopic identification of diatom species. We compared the diatom index derived from eDNA data obtained with or without taxonomic assignment. Our taxonomy‐free approach yields promising results by providing a correct assessment for 77% of examined sites. The main advantage of this method is that almost 95% of OTUs could be used for index calculation, compared to 35% in the case of the taxonomic assignment approach. Its main limitations are under‐sampling and the need to calibrate the index based on the microscopic assessment of diatoms communities. However, once calibrated, the taxonomy‐free molecular index can be easily standardized and applied in routine biomonitoring, as a complementary tool allowing fast and cost‐effective assessment of the biological quality of watercourses.
Friends and family: A software program for identification of unrelated individuals from molecular marker data

The identification of related and unrelated individuals from molecular marker data is often difficult, particularly when no pedigree information is available and the data set is large. High levels of relatedness or inbreeding can influence genotype frequencies and thus genetic marker evaluation, as well as the accurate inference of hidden genetic structure. Identification of related and unrelated individuals is also important in breeding programmes, to inform decisions about breeding pairs and translocations. We present Friends and Family, a Windows executable program with a graphical user interface that identifies unrelated individuals from a pairwise relatedness matrix or table generated in programs such as coancestry and genalex. Friends and Family outputs a list of samples that are all unrelated to each other, based on a user‐defined relatedness cut‐off value. This unrelated data set can be used in downstream analyses, such as marker evaluation or inference of genetic structure. The results can be compared to that of the full data set to determine the effect related individuals have on the analyses. We demonstrate one of the applications of the program: how the removal of related individuals altered the Hardy–Weinberg equilibrium test outcome for microsatellite markers in an empirical data set. Friends and Family can be obtained from https://github.com/DeondeJager/Friends-and-Family.
Zika virus in asymptomatic blood donors in Martinique.

Zika fever is an Aedes-borne disease caused by a flavivirus (Zika virus, ZIKV, genus Flavivirus). During the past years ZIKV spread in Polynesia, South-America and the Caribbean. Most ZIKV infections are asymptomatic or result in mild febrile disease with rash and conjunctivitis. Attention was recently drawn to non-vectored ZIKV transmission, including sexual, probable blood-borne and mother-to-fetus transmission, and to severe forms such as Guillain-Barre syndrome, acute neurological infections and fetal abnormalities (including microcephaly). Many aspects of Zika fever natural history remain unknown, e.g. the proportion of asymptomatic cases and the duration of viremia. Estimating the prevalence of Zika infections is difficult because a large proportion of infected individuals do not seek medical attention and seroprevalence studies are hampered by antigenic cross-reactivity with other flaviviruses, e.g. dengue virus. Here, we present a study of ZIKV infection in blood donors from Martinique island (French West Indies, Caribbean region), with novel epidemiological, biological and clinical information that refine the picture of Zika fever in adults.
Robustness and sensitivity of hotelling's T2-based permutation tests for selection of 3D morphological markers

Multivariate statistics are a powerful tool to analyze morphological changes in three-dimensional brain structures. The Hotelling's T2 (HT2) statistic has previously been used to this purpose. HT2 is a parametric test which assumes normal distribution of the data: when this does not hold, as often happens for shape analysis, the test can still be used as basis for nonparametric permutation tests (PT). In their approximate version, PT are nondeterministic, being affected by the randomly pooled subset of permutations. In this study, we investigate the sensitivity and robustness of HT2-based PT, with respect to nondeterministic effects, both on simulated data and a medical application: the detection of hippocampal morphological changes to accurately predict conversion to Alzheimer's disease. The sensitivity of PT increases significantly with larger sample size, while is less dependent on the number of permutations. Moreover, PT provides statistically consistent classification performances: 80% accuracy in predicting conversion to Alzheimer's disease.
Effects of an intervention program of physical activity and nutrition orientation on the physical activity level of physically active women aged 50 to 72 years old

A promocao do estilo de vida mais ativo na terceira idade tem sido utilizada como estrategia de desenvolver melhora nos padroes de saude e na qualidade de vida. O objetivo do presente estudo foi verificar o efeito de um programa de orientacao de atividade fisica (AF) e nutricional sobre o nivel de atividade fisica (NAF) de mulheres fisicamente ativas. A amostra foi composta de 64 senhoras de 50 a 72 anos de idade de Sao Caetano do Sul que participavam de um programa regular de ginastica. As senhoras foram alocadas em um dos quatro grupos: A) nutricao (n: 17); B) nutricao + atividade fisica (n: 17); C) atividade fisica (n: 13); D) controle (n: 15). Para avaliar o NAF foi utilizado o Questionario Internacional de Atividade Fisica IPAQ. O programa de intervencao foi realizado durante 12 semanas, uma vez por semana, por 5 a 10 minutos apos as aulas de ginastica. As orientacoes nutricionais foram baseadas na nutricao saudavel e as de AF fundamentadas na mensagem do Agita Sao Paulo, que estimula, pelo menos 30 minutos por dia, na maior parte dos dias da semana, de forma continua ou acumulada, atividades fisicas em intensidade moderada, alem das aulas de ginastica. Os resultados indicaram aumento na frequencia (vezes/semana) das atividades moderadas (32,4%; 49,6%; 47,9%; p < 0,05) nos grupos A, B e C, respectivamente, apos 12 semanas de intervencao, em comparacao com o controle. As senhoras que receberam orientacao de AF aumentaram significativamente a duracao das atividades moderadas em 123,2% e da caminhada em 150,9% e tambem a frequencia da caminhada (97,6%) em relacao aos valores pre-intervencao. O presente estudo demonstrou que o programa de intervencao promoveu aumento significativo do NAF ate mesmo em senhoras irregularmente ativas.
Ilastik: Interactive learning and segmentation toolkit

Segmentation is the process of partitioning digital images into meaningful regions. The analysis of biological high content images often requires segmentation as a first step. We propose ilastik as an easy-to-use tool which allows the user without expertise in image processing to perform segmentation and classification in a unified way. ilastik learns from labels provided by the user through a convenient mouse interface. Based on these labels, ilastik infers a problem specific segmentation. A random forest classifier is used in the learning step, in which each pixel's neighborhood is characterized by a set of generic (nonlinear) features. ilastik supports up to three spatial plus one spectral dimension and makes use of all dimensions in the feature calculation. ilastik provides realtime feedback that enables the user to interactively refine the segmentation result and hence further fine-tune the classifier. An uncertainty measure guides the user to ambiguous regions in the images. Real time performance is achieved by multi-threading which fully exploits the capabilities of modern multi-core machines. Once a classifier has been trained on a set of representative images, it can be exported and used to automatically process a very large number of images (e.g. using the CellProfiler pipeline). ilastik is an open source project and released under the BSD license at www.ilastik. org.
A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma.

This phase 1b, open-label, dose-escalation study assessed the safety, efficacy, and pharmacokinetics of anti-CD38 monoclonal antibody isatuximab given in 2 schedules (3, 5, or 10 mg/kg every other week [Q2W] or 10 or 20 mg/kg weekly [QW] for 4 weeks and then Q2W thereafter [QW/Q2W]), in combination with lenalidomide 25 mg (days 1-21) and dexamethasone 40 mg (QW), in patients with relapsed/refractory multiple myeloma (RRMM). Patients received 28-day treatment cycles; the primary objective was to determine the maximum tolerated dose (MTD) of isatuximab with lenalidomide and dexamethasone. Fifty-seven patients (median 5 [range 1-12] prior regimens; 83% refractory to previous lenalidomide therapy) were treated. Median duration of dosing was 36.4 weeks; 15 patients remained on treatment at data cutoff. Isatuximab-lenalidomide-dexamethasone was generally well tolerated with only 1 dose-limiting toxicity reported (grade 3 pneumonia at 20 mg/kg QW/Q2W); the MTD was not reached. The most common isatuximab-related adverse events were infusion-associated reactions (IARs) (56%), which were grade 1/2 in 84% of patients who had an IAR and predominantly occurred during the first infusion. In the efficacy-evaluable population, the overall response rate (ORR) was 56% (29/52) and was similar between the 10 mg/kg Q2W and 10 and 20 mg/kg QW/Q2W cohorts. The ORR was 52% in 42 evaluable lenalidomide-refractory patients. Overall median progression-free survival was 8.5 months. Isatuximab exposure increased in a greater than dose-proportional manner; isatuximab and lenalidomide pharmacokinetic parameters appeared independent. These data suggest that isatuximab combined with lenalidomide and dexamethasone is active and tolerated in heavily pretreated patients with RRMM. This trial was registered at www.clinicaltrials. gov as #NCT01749969.
Is There an Association between Levels of Bovine Tuberculosis in Cattle Herds and Badgers?

Wildlife diseases can have undesirable effects on wildlife, on livestock and people. Bovine tuberculosis (TB) is such a disease. This study derives and then evaluates relationships between the proportion of cattle herds with newly detected TB infection in a year and data on badgers, in parts of Britain.The relationships are examined using data from 10 sites which were randomly selected to be proactive culling sites in the UK Randomized Badger Culling Trial. The badger data are from the initial cull only and the cattle incidence data pre-date the initial badger cull.The analysis of the proportion of cattle herds with newly detected TB infection in a year, showed strong support for the model including significant frequency-dependent transmission between cattle herds and significant badger-to-herd transmission proportional to the proportion of M. bovis-infected badgers. Based on the model best fitting all the data, 3.4% of herds (95% CI: 0  6.7%) would be expected to have TB infection newly detected (i.e. to experience a TB herd breakdown) in a year, in the absence of transmission from badgers. Thus, the null hypothesis that at equilibrium herd-to-herd transmission is not sufficient to sustain TB in the cattle population, in the absence of transmission from badgers cannot be rejected (p=0.18). Omitting data from three sites in which badger carcase storage may have affected data quality; the estimate dropped to 1.3% of herds (95% CI: 0  6.5%) with p=0.76. The results demonstrate close positive relationships between bovine TB in cattle herds and badgers infectious with M. bovis. The results indicate that TB in cattle herds could be substantially reduced, possibly even eliminated, in the absence of transmission from badgers to cattle. The results are based on observational data and a small data set to provide weaker inference than from a large experimental study.
HDAC2 mediates therapeutic resistance of pancreatic cancer cells via the BH3-only protein NOXA

Background: Although histone deacetylase inhibitors (HDACi) are promising cancer therapeutics regulating proliferation, differentiation and apoptosis, molecular pathways engaged by specific HDAC isoenzymes in cancer are ill defined. Results: In this study we demonstrate that HDAC2 is highly expressed in pancreatic ductal adenocarcinoma (PDAC), especially in undifferentiated tumours. We show that HDAC2, but not HDAC1, confers resistance towards the topoisomerase II inhibitor etoposide in PDAC cells. Correspondingly, the class I selective HDACi valproic acid (VPA) synergises with etoposide to induce apoptosis of PDAC cells. Transcriptome profiling of HDAC2-depleted PDAC cells revealed upregulation of the BH3-only protein NOXA. We show that the epigenetically silenced NOXA gene locus is opened after HDAC2 depletion and that NOXA upregulation is sufficient to sensitise PDAC cells towards etoposide-induced apoptosis. Conclusions: In summary, our data characterise a novel molecular mechanism that links the epigenetic regulator HDAC2 to the regulation of the pro-apoptotic BH3-only protein NOXA in PDAC. Targeting HDAC2 will therefore be a promising strategy to overcome therapeutic resistance of PDAC against chemotherapeutics that induce DNA damage.
Radiation-free, alternative-donor HCT for Fanconi anemia patients: results from a prospective multi-institutional study.

Fanconi anemia (FA) is an inherited bone marrow failure syndrome characterized by chromosomal fragility, progressive marrow failure, and cancer predisposition. Hematopoietic cell transplantation (HCT) is curative for FA-related marrow failure or leukemia, but both radiation exposure during transplant and graft-versus-host disease (GVHD) may increase risk of later malignancies of the head and neck and anogenital area. In this study, we tested a radiation-free conditioning regimen with a T-cell-depleted graft to eliminate radiation exposure and minimize early and late toxicities of transplant. Forty-five patients (median age, 8.2 years; range 4.3-44) with FA underwent HCT between June 2009 and May 2014. The preparative regimen included busulfan, cyclophosphamide, fludarabine, and rabbit anti-thymocyte globulin. Busulfan levels were monitored to avoid excess toxicity. All grafts were CD34-selected/T-cell-depleted using the CliniMacs CD34 columns (Miltenyi). Thirty-four patients (75.6%) with marrow failure and 11 (24.4%) with myelodysplastic syndrome underwent HCT using matched unrelated (n = 25, 55.5%), mismatched unrelated (n = 14, 31.1%), or mismatched related donors (n = 6, 13.4%). One year probabilities of overall and disease-free survival for the entire cohort, including patients with myeloid malignancy and those receiving mismatched related/haploidentical grafts, were 80% (±6%) and 77.7% (±6.2%), respectively (median follow-up 41 months). All young children (<10 years of age) undergoing HCT for marrow failure using low-dose busulfan-containing regimen survived. No patients developed acute grade 3-4 GVHD. Sequential reduction of busulfan dose was successfully achieved per study design. Our results show excellent outcomes in patients with FA undergoing alternative donor HCT without radiation exposure. The study is registered to www.clinicaltrials. gov as #NCT01082133.
Idiopathic Low Back Pain: Classification and Differential Diagnosis

SUMMARY Objectives: To present a contemporary view of the epidemiology, classification, and differential diagnosis of low back pain. Findings: With age, the normal back will exhibit visible morphological changes. Thus, idiopathic low back pain cannot be directly related to the morphological picture, but is influenced by many factors related to ligaments, discs, muscles and nerves. Idiopathic low back pain is experienced in about two-thirds of the population over their life time and about half of the adult population will suffer from back pain at some time during a 12 months period. The cost to society for work absenteeism related to back pain is very high. There are a variety of systems for classifying back pain which do not always overlap, and which have different aims. The process of diagnosing back pain consists of clinical examination, various types of imaging, and laboratory tests. Imaging methods have improved greatly. For example, imaging can identify disc related problems, so patients with those lesions can be excluded from the idiopathic low back pain group. Despite improved methods, however, it is usually difficult to specify the cause of the low back pain, and it is still impossible to accurately perceive its severity. Conclusions: Although acute back pain is often viewed as a benign and reversible condition, it can develop into a chronic condition if not correctly diagnosed and treated accordingly.