Sliding window multi-curve resolution: application to gas chromatography - ion mobility spectrometry

Blind source separation (BSS) techniques aim to extract a set of source signals from a measured mixture in an unsupervised manner. In the chemical instrumentation domain source signals typically refer to time-varying analyte concentrations, while the measured mixture is the set of observed spectra. Several techniques exist to perform BSS on ion mobility spectrometry, being simple-to-use interactive self-modelling mixture analysis (SIMPLISMA) and multivariate curve resolution (MCR) the most commonly used. The addition of a multi-capillary gas chromatography column using the ion mobility spectrometer as detector has been proposed in the past to increase chemical resolution. Short chromatography times lead to high levels of co-elution, and ion mobility spectra are key to resolve them. For the first time, BSS techniques are used to deconvolve samples of the gas chromatography-ion mobility spectrometry tandem. We propose a method to extract spectra and concentration profiles based on the application of MCR in a sliding window. Our results provide clear concentration profiles and pure spectra, resolving peaks that were not detected by the conventional use of MCR. The proposed technique could also be applied to other hyphenated instruments with similar strong co-elutions

Weaker HLA footprints on HIV in the unique and highly genetically admixed host population of Mexico

HIV circumvents HLA class I-restricted CD8+ T-cell responses through selection of escape mutations that leave characteristic mutational “footprints,” also known as HLA-associated polymorphisms (HAPs), on HIV sequences at the population level. While many HLA footprints are universal across HIV subtypes and human populations, others can be region specific as a result of the unique immunogenetic background of each host population. Using a published probabilistic phylogenetically informed model, we compared HAPs in HIV Gag and Pol (PR-RT) in 1,612 subtype B-infected, antiretroviral treatment-naive individuals from Mexico and 1,641 individuals from Canada/United States. A total of 252 HLA class I allele subtypes were represented, including 140 observed in both cohorts, 67 unique to Mexico, and 45 unique to Canada/United States. At the predefined statistical threshold of a q value of <0.2, 358 HAPs (201 in Gag, 157 in PR-RT) were identified in Mexico, while 905 (534 in Gag and 371 in PR-RT) were identified in Canada/United States. HAPs identified in Mexico included both canonical HLA-associated escape pathways and novel associations, in particular with HLA alleles enriched in Amerindian and mestizo populations. Remarkably, HLA footprints on HIV in Mexico were not only fewer but also, on average, significantly weaker than those in Canada/United States, although some exceptions were noted. Moreover, exploratory analyses suggested that the weaker HLA footprint on HIV in Mexico may be due, at least in part, to weaker and/or less reproducible HLA-mediated immune pressures on HIV in this population. The implications of these differences for natural and vaccine-induced anti-HIV immunity merit further investigation

Clinical-epidemiologic variation in patients treated in the first and second wave of COVID-19 in Lambayeque, Peru: A cluster analysis

"Objectives: To identify differences in the clinical and epidemiologic characteristics of patients during the first and second waves of the COVID-19 pandemic at the EsSalud Lambayeque health care network, Peru. Methods: An analytical cross-sectional study of 53,912 patients enrolled during the first and second waves of COVID-19 was conducted. Cluster analysis based on clustering large applications (CLARA) was applied to clinical-epidemiologic data presented at the time of care. The two pandemic waves were compared using clinical-epidemiologic data from epidemiologic surveillance. Results: Cluster analysis identified four COVID-19 groups with a characteristic pattern. Cluster 1 included the largest number of participants in both waves, and the participants were predominantly female. Cluster 2 included patients with gastrointestinal, respiratory, and systemic symptoms. Cluster 3 was the “severe” cluster, characterized by older adults and patients with dyspnea or comorbidities (cardiovascular, diabetes, obesity). Cluster 4 included asymptomatic, pregnant, and less severe patients. We found differences in all clinical-epidemiologic characteristics according to the cluster to which they belonged. Conclusion: Using cluster analysis, we identified characteristic patterns in each group. Respiratory, gastrointestinal, dyspnea, anosmia, and ageusia symptoms were higher in the second COVID-19 wave than the first COVID-19 wave

ALMA-IMF. VII. First release of the full spectral line cubes: Core kinematics traced by DCN J=(3-2)

ALMA-IMF is an Atacama Large Millimeter/submillimeter Array (ALMA) Large Program designed to measure the core mass function (CMF) of 15 protoclusters chosen to span their early evolutionary stages. It further aims to understand their kinematics, chemistry, and the impact of gas inflow, accretion, and dynamics on the CMF. We present here the first release of the ALMA-IMF line data cubes (DR1), produced from the combination of two ALMA 12m-array configurations. The data include 12 spectral windows, with eight at 1.3mm and four at 3mm. The broad spectral coverage of ALMA-IMF (~6.7 GHz bandwidth coverage per field) hosts a wealth of simple atomic, molecular, ionised, and complex organic molecular lines. We describe the line cube calibration done by ALMA and the subsequent calibration and imaging we performed. We discuss our choice of calibration parameters and optimisation of the cleaning parameters, and we demonstrate the utility and necessity of additional processing compared to the ALMA archive pipeline. As a demonstration of the scientific potential of these data, we present a first analysis of the DCN (3-2) line. We find that DCN traces a diversity of morphologies and complex velocity structures, which tend to be more filamentary and widespread in evolved regions and are more compact in the young and intermediate-stage protoclusters. Furthermore, we used the DCN (3-2) emission as a tracer of the gas associated with 595 continuum cores across the 15 protoclusters, providing the first estimates of the core systemic velocities and linewidths within the sample. We find that DCN (3-2) is detected towards a higher percentage of cores in evolved regions than the young and intermediate-stage protoclusters and is likely a more complete tracer of the core population in more evolved protoclusters. The full ALMA 12m-array cubes for the ALMA-IMF Large Program are provided with this DR1 release.Comment: 75 pages (21 main body; 54 appendix), 37 figures. The ALMA-IMF DR1 line release is hosted at https://dataverse.harvard.edu/dataverse/alma-im

Novel CTCF binding at a site in exon1A of BCL6 is associated with active histone marks and a transcriptionally active locus

BCL6 is a zinc-finger transcriptional repressor, which is highly expressed in germinal centre B-cells and is essential for germinal centre formation and T-dependent antibody responses. Constitutive BCL6 expression is sufficient to produce lymphomas in mice. Deregulated expression of BCL6 due to chromosomal rearrangements, mutations of a negative autoregulatory site in the BCL6 promoter region and aberrant post-translational modifications have been detected in a number of human lymphomas. Tight lineage and temporal regulation of BCL6 is, therefore, required for normal immunity, and abnormal regulation occurs in lymphomas. CCCTC-binding factor (CTCF) is a multi-functional chromatin regulator, which has recently been shown to bind in a methylation-sensitive manner to sites within the BCL6 first intron. We demonstrate a novel CTCF-binding site in BCL6 exon1A within a potential CpG island, which is unmethylated both in cell lines and in primary lymphoma samples. CTCF binding, which was found in BCL6-expressing cell lines, correlated with the presence of histone variant H2A.Z and active histone marks, suggesting that CTCF induces chromatin modification at a transcriptionally active BCL6 locus. CTCF binding to exon1A was required to maintain BCL6 expression in germinal centre cells by avoiding BCL6-negative autoregulation. Silencing of CTCF in BCL6-expressing cells reduced BCL6 mRNA and protein expression, which is sufficient to induce B-cell terminal differentiation toward plasma cells. Moreover, lack of CTCF binding to exon1A shifts the BCL6 local chromatin from an active to a repressive state. This work demonstrates that, in contexts in which BCL6 is expressed, CTCF binding to BCL6 exon1A associates with epigenetic modifications indicative of transcriptionally open chromatin

Primary care randomized clinical trial: manual therapy effectiveness in comparison with TENS in patients with neck pain

This study investigated effectiveness of manual therapy (MT) with transcutaneous electrical nerve stimulation (TENS) to reduce pain intensity in patients with mechanical neck disorder (MND). A randomized multi-centered controlled clinical trial was performed in 12 Primary Care Physiotherapy Units in Madrid Region. Ninety patients were included with diagnoses of subacute or chronic MND without neurological damage, 47 patients received MT and 43 TENS. The primary outcome was pain intensity measured in millimeters using the Visual Analogue Scale (VAS). Also disability, quality of life, adverse effects and sociodemographic and prognosis variables were measured. Three evaluations were performed (before, when the procedure ?nished and six months after). Seventy-one patients (79%) completed the follow-up measurement at six months. In more than half of the treated patients the procedure had a clinically relevant ?short term? result after having ended the intervention, when either MT or TENS was used. The success rate decreased to one-third of the patients 6 months after the intervention. No differences can be found in the reduction of pain, in the decrease of disability nor in the quality of life between both therapies. Both analyzed physiotherapy techniques produce a short-term pain reduction that is clinically relevant.Ministerio de SanidadInstituto de Salud Carlos II

Is there a role for melatonin in fibromyalgia?

Fibromyalgia, characterised by persistent pain, fatigue, sleep disturbance and cognitive dysfunction, is a central sensitivity syndrome that also involves abnormality in peripheral generators and in the hypothalamic pituitary adrenal axis. Heterogeneity of clinical expression of fibromyalgia with a multifactorial aetiology has made the development of effective therapeutic strategies challenging. Physiological properties of the neurohormone melatonin appear related to the symptom profile exhibited by patients with fibromyalgia and thus disturbance of it’s production would be compatible with the pathophysiology. Altered levels of melatonin have been observed in patients with fibromyalgia which are associated with lower secretion during dark hours and higher secretion during daytime. However, inconsistencies of available clinical evidence limit conclusion of a relationship between levels of melatonin and symptom profiles in patients with fibromyalgia. Administration of melatonin to patients with fibromyalgia has demonstrated suppression of many symptoms and an improved quality of life consistent with benefit as a therapy for the management of this condition. Further studies with larger samples, however, are required to explore the potential role of melatonin in the pathophysiology of fibromyalgia and determine the optimal dosing regimen of melatonin for the management of fibromyalgia