Miracle-dz/UniFAR-FTUs huggingface dataset:
Voice bubbling therapy for vocal cord dysfunction in difficult-to-treat asthma – a pilot study

Abstract Objective Dysfunctional breathing often coexists with asthma and complicates asthma control, especially in difficult-to-treat asthma. Voice bubbling therapy (VBT) by a specialized speech therapist may influence the breathing pattern. This pilot study investigated the effect of voice bubbling therapy (VBT) in participants with difficult-to-treat asthma, who fulfilled criteria for dysfunctional breathing pattern. Method Twenty-four patients were randomized between VBT and usual care (UC). VBT is blowing into a glass (resonance) tube (28 cm in length, 0.9 cm inner diameter) which ends in a bowl of water (1.5 litre). Lung function, capillary blood gas and questionnaires were measured at baseline, at 6 and 18 weeks of follow up. Results No difference in ACQ and quality of life was found after VBT compared to UC group. However, after six weeks of bubbling therapy, pCO2 levels measured in capillary blood gas were higher (baseline median (IQR) pCO2 = 33.00 (17.25 − 38.6) mmHg; week 6 pCO2 = 36.00 (29.00 − 42.3) mmHg) p = 0.01. Moreover, ΔpCO2 (baseline − 18 weeks of follow up) was significantly correlated with ΔAQLQ (rs = 0.78, p = 0.02). Conclusion VBT in participants with difficult-to-treat asthma resulted in a higher average pCO2 level, indicating the treatment may improve hyperventilation. However, this did not improve asthma control or quality of life. VBT may have value for a better management of asthma related symptoms.
Semicircular Patch-Embedded Vivaldi Antenna for Miniaturized UWB Radar Sensors

A microstrip-to-slot line-fed miniaturized Vivaldi antenna using semicircular patch embedment is proposed in this study. The conventional Vivaldi antenna has ultrawide bandwidth, but suffers from low gain in the low-frequency band. The proposed antenna topology incorporates the embedment of semicircular patch elements into the side edge of the antenna. This enables the phases of electric fields at both ends of the antenna to be out of phase. Since the distance between the two ends are λL/2 where λL is the wavelength at a low operating frequency, this antenna topology can achieve the constructive addition of electrical fields at the radiating end, leading to gain enhancement at the chosen low frequency. In comparison with the conventional Vivaldi antenna, the proposed antenna has a wider bandwidth from 2.84 to 9.83 GHz. Moreover, the simulated result shows a gain enhancement of 5 dB at low frequency. This cannot be realized by the conventional low-band impedance matching techniques only relying on slotted topologies. The measured results of this proposed antenna with a size of 45 × 40 × 0.8 mm3 are in good agreement with the simulated results.
Molecular Characterization of Fenugreek (Trigonella foenum-graecum L.) Genotypes Using Rapd Markers

The genus Trigonella is one of the largest genera of the tribe Trifoliatae in the family Fabaceae (Balodi et al., 1991). It is a flowering annual, with autogamous white flowers occasionally visited by insects and is originated in the eastern shores of Mediterranean region. Fenugreek is widely cultivated in India, Egypt, Ethiopia, Morocco and occasionally in England (Polhil et al., 1981). It is widely cultivated in the tropical and subtropical regions of India. Fenugreek is rich in minerals, protein, vitamin A and C. For any crop improvement program the basic requirement is availability of germplasm with wide variability. Germplasm pool is an important source of variability for developing new cultivars having good economic traits. Hence, assessment of genetic divergence in fenugreek germplasm is important for long term crop improvement programme.
Sources and priming of N2 O production across a range of moisture contents in a soil with high organic matter.

Adding nitrogen fertilizers to agricultural soils contributes to increasing concentrations of nitrous oxide (N2 O) in the atmosphere. However, the impacts of N addition on soil organic matter (SOM) turnover, SOM availability, and the ensuing SOM-derived N2 O emissions remain elusive. Within this context, the net change in direction and rate of SOM-derived N2 O production triggered by added N is termed the N2 O priming effect. This incubation study examined the sources and priming of N2 O production as a function of urea addition and multiple moisture contents in a soil with high SOM (55 g organic C kg-1 ). We assessed four water-filled pore space (WFPS) conditions: 28, 40, 52, and 64%. Relative to controls receiving no N, urea addition increased N2 O production by 2.6 times (P < 0.001). Cumulative N2 O production correlated well with nitrification rates (r = 0.75, P = 0.03). We used 15 N-labelled urea to trace the added urea into N2 O. Of the N added via urea, the recovery as N2 O-N shifted from 0.02 to 0.17% when WFPS increased from 28 to 64% (P < 0.05). We also partitioned the N2 O production into urea versus SOM sources. More N2 O was sourced from SOM than urea, with 59 ± 2% N2 O originating from SOM. The magnitude of SOM-derived N2 O under urea was larger than that of the control, revealing that positive N2 O priming was triggered by urea addition. Upon subtracting the controls, the primed N2 O was a consistent 19 ± 2% of the total N2 O produced by urea-amended soils. Nevertheless, the priming magnitude rose sharply with increasing moisture by more than one order of magnitude from 4 to 48 μg N2 O-N kg-1 soil, and in exponential mode (R2 = 0.98). Soil moisture, SOM, and nitrification interacted to drive the sources and priming of N2 O. This article is protected by copyright. All rights reserved.
Differential Neuropsychological Profile of Patients With Amyotrophic Lateral Sclerosis With and Without C9orf72 Mutation

Objective To determine whether the neuropsychological profiles of patients with amyotrophic lateral sclerosis (ALS) with (ALSC9+) and without (ALSC9−) C9orf72 expansion are different, we administered a battery of neuropsychological tests to 741 patients with ALS (68 ALSC9+ and 673 ALSC9−) and 129 controls. Methods The study population includes 741 patients with ALS who were consecutively diagnosed at the Turin ALS expert center in the 2010–2018 period and who underwent both cognitive/behavioral and genetic testing. Patients' neuropsychological patterns were compared (1) at the same degree of cognitive and behavioral deficit according to the revised ALS–Frontotemporal Dementia Consensus Criteria and (2) at the same level of motor impairment according to the King staging system. Results Despite being about 7 years younger, ALSC9+ patients had significantly lower scores in tests exploring executive function and verbal memory both when classified as cognitively normal and when diagnosed in the intermediate cognitive categories. Considering the clinical perspective, ALSC9+ patients showed significantly lower scores compared to ALSC9− patients at King stage 1 and 3 in almost all the examined neuropsychological domains; at King stage 2, ALSC9+ patients were more severely affected only in the verbal memory domain. Behavioral function was comparably impaired in the 2 cohorts. Conclusions ALSC9+ patients show a different neuropsychological profile compared to ALSC9− patients, being more impaired in executive functions and verbal memory domains at all King stages. Verbal memory emerged as a particularly vulnerable function in ALSC9+, with worse performances even when patients were still classified as cognitively normal.
Directed co-evolution of interacting protein–peptide pairs by compartmentalized two-hybrid replication (C2HR)

Abstract Directed evolution methodologies benefit from read-outs quantitatively linking genotype to phenotype. We therefore devised a method that couples protein–peptide interactions to the dynamic read-out provided by an engineered DNA polymerase. Fusion of a processivity clamp protein to a thermostable nucleic acid polymerase enables polymerase activity and DNA amplification in otherwise prohibitive high-salt buffers. Here, we recapitulate this phenotype by indirectly coupling the Sso7d processivity clamp to Taq DNA polymerase via respective fusion to a high affinity and thermostable interacting protein–peptide pair. Escherichia coli cells co-expressing protein–peptide pairs can directly be used in polymerase chain reactions to determine relative interaction strengths by the measurement of amplicon yields. Conditional polymerase activity is further used to link genotype to phenotype of interacting protein–peptide pairs co-expressed in E. coli using the compartmentalized self-replication directed evolution platform. We validate this approach, termed compartmentalized two-hybrid replication, by selecting for high-affinity peptides that bind two model protein partners: SpyCatcher and the large fragment of NanoLuc luciferase. We further demonstrate directed co-evolution by randomizing both protein and peptide components of the SpyCatcher–SpyTag pair and co-selecting for functionally interacting variants.
Attachment and Executive Functions in ADHD Symptomatology—Independent Inputs or an Interaction?

Despite a multitude of research on executive functions and attachment in Attention Deficit Hyperactivity Disorder (ADHD), a synthetic approach to the matter seems to have been lacking. In this review, we attempt to check the available data against two hypotheses: (1) executive functions and attachment influence ADHD symptoms independently; (2) executive functions and attachment interact to produce ADHD symptoms. We found no evidence falsifying the former hypothesis and some evidence to refute the latter. Limitations of current study approaches and suggestions for further research are discussed. Specifically, we propose an attachment representation, rather than attachment style, approach to measuring the mediation thereof between executive dysfunctions and ADHD.
Characterisation of cultured airway basal cells to understand their role in human lung disease

Many studies in murine models have demonstrated the stem/progenitor cell potential of basal epithelial cells in the tracheal epithelium. However, significant differences exist between the respiratory epithelium in rodents and in man. As such, novel methodologies to study respiratory epithelial cells in vitro are in demand. Here, methods to expand primary human airway epithelial cells from living patients were explored. The field’s ‘gold standard’ medium for the expansion of these cells was poorly suited to initiating cultures from small endobronchial biopsy samples as proliferation of these cells was time-limited and after a short period of time in culture the cells became senescent and were unable to regenerate a mucociliary epithelium in organotypic models. As such, an alternative epithelial culture strategy involving the co-culture of human airway epithelial cells with 3T3-J2 fibroblast feeder cells in medium containing a small molecule Rho-associated protein kinase (ROCK) inhibitor was assessed. This method greatly improved both the yield and the longevity of human basal cell cultures and allowed multipotent airway differentiation in organotypic assays after longer culture periods than conventional techniques. Finally, the epithelial-stromal cell crosstalk between epithelial cells and feeder cells in co-culture was investigated, revealing a novel signalling pathway involving phosphorylation of the transcription factor signal transducer and activator of transcription 6 (STAT6) by hepatocyte growth factor (HGF) signalling.
Gender Strategies and Sex-ratio Evolution in the Clonal Aquatic Plant: Sagittaria latifolia (Alismataceae)

Flowering plants display diverse reproductive systems, including a variety of gender strategies and mechanisms of clonal propagation. Here, I investigate gender strategies, sex-ratio evolution, and sexual dimorphism in the North American clonal aquatic, Sagittaria latifolia (Alismataceae), which exhibits three sex phenotypes (hermaphrodites, females, males) and two modal sexual systems (monoecy, dioecy). This provides an outstanding opportunity to examine the costs and benefits of combined versus separate sexes. My research focused on the northern range limit in eastern N. America, and on disjunct populations in western N. America. I developed microsatellite (SSR) markers to investigate population genetic structure at several spatial scales, including the clonal structure of local populations to continental patterns. These analyses provided insights on the roles of historical, ecological and reproductive factors in the evolution and maintenance of sexual system diversity. Phenotypic sex ratios varied near continuously from monoecy through subdioecy (three sex phenotypes) to dioecy. A comparison of phenotypic and iii genotypic sex ratios in dioecious populations demonstrated close correspondence. The northern range limit was characterized by a decline in female frequency and an increased incidence of subdioecy. I evaluated two hypotheses to explain this pattern: (1) increased sex inconstancy in dioecious populations; (2) hybridization between monoecious and dioecious populations. I found support for both hypotheses, although hybridization appears to be the more common pathway to subdioecy. I parameterized a model predicting female frequency and hermaphrodite sex allocation; observed and predicted values were correlated suggesting that subdioecious populations are closer to equilibrium than expected for a clonal perennial. A comparison of eastern and western populations indicated genetic differentiation between monoecy and dioecy in the east, but in the west, due to habitat isolation, geography plays a more important role in genetic differentiation. Evidence from cpDNA haplotype variation indicated that the western range was established following long-distance colonization from the east involving a genetic bottleneck. The discovery of gynodioecious populations of S. latifolia in the west, and the absence of ecological and genetic differentiation between monoecious and dioecious populations, raise the possibility that dioecy may have evolved autochthonously in the west, and more recently than in the eastern range.
Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease.

BACKGROUND Adult-onset inflammatory syndromes often manifest with overlapping clinical features. Variants in ubiquitin-related genes, previously implicated in autoinflammatory disease, may define new disorders. METHODS We analyzed peripheral-blood exome sequence data independent of clinical phenotype and inheritance pattern to identify deleterious mutations in ubiquitin-related genes. Sanger sequencing, immunoblotting, immunohistochemical testing, flow cytometry, and transcriptome and cytokine profiling were performed. CRISPR-Cas9-edited zebrafish were used as an in vivo model to assess gene function. RESULTS We identified 25 men with somatic mutations affecting methionine-41 (p.Met41) in UBA1, the major E1 enzyme that initiates ubiquitylation. (The gene UBA1 lies on the X chromosome.) In such patients, an often fatal, treatment-refractory inflammatory syndrome develops in late adulthood, with fevers, cytopenias, characteristic vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow, neutrophilic cutaneous and pulmonary inflammation, chondritis, and vasculitis. Most of these 25 patients met clinical criteria for an inflammatory syndrome (relapsing polychondritis, Sweet's syndrome, polyarteritis nodosa, or giant-cell arteritis) or a hematologic condition (myelodysplastic syndrome or multiple myeloma) or both. Mutations were found in more than half the hematopoietic stem cells, including peripheral-blood myeloid cells but not lymphocytes or fibroblasts. Mutations affecting p.Met41 resulted in loss of the canonical cytoplasmic isoform of UBA1 and in expression of a novel, catalytically impaired isoform initiated at p.Met67. Mutant peripheral-blood cells showed decreased ubiquitylation and activated innate immune pathways. Knockout of the cytoplasmic UBA1 isoform homologue in zebrafish caused systemic inflammation. CONCLUSIONS Using a genotype-driven approach, we identified a disorder that connects seemingly unrelated adult-onset inflammatory syndromes. We named this disorder the VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. (Funded by the NIH Intramural Research Programs and the EU Horizon 2020 Research and Innovation Program.).
Efficacy of Oxyclozanide and Closantel against Rumen Flukes (Paramphistomidae) in Naturally Infected Sheep

Simple Summary Paramphistomosis, caused by ruminal trematodes, is currently considered an emergent disease in Europe due to the progressive increase of prevalence and reports of acute cases in ruminants. Thus, finding effective control methods such as efficient drugs against paramphistomids is currently a priority. Although some drugs have been found effective for treating paramphistomid infections in cattle, data in sheep are currently limited. A single administration of oxyclozanide (15 mg/kg) or closantel (10 mg/kg) has been proven efficient in cattle, but it has not been tested in sheep; thus, the aim of the present study was to assess the effectiveness of these treatment protocols against paramphistomids in naturally infected sheep. The treatment with oxyclozanide was very efficient since it significantly reduced the paramphistomid egg output in more than 90% during 11 weeks after treatment. In contrast, closantel showed low efficacies throughout the study. The results of this study support the use of a single oral dose of oxyclozanide at 15 mg/kg for treating paramphistomid infections in sheep, whereas a single oral dose of closantel at 10 mg/kg is not effective. Abstract Paramphistomosis is considered an emergent disease of ruminants in Europe. Some drugs have been found effective for treating paramphistomid infections in cattle, but data in sheep are currently limited. Thus, faecal samples from 25 adult sheep naturally infected with paramphistomids were collected weekly to test the efficacy of oxyclozanide and closantel. Three groups were performed: nine animals orally treated with a single dose of oxyclozanide (15 mg/kg bodyweight (BW) integrated the G-OXI group, whereas eight sheep orally treated with a single dose of closantel (10 mg/kg BW) were placed in a group called G-CLS. Eight untreated controls constituted the group G-CON. Oxyclozanide showed efficacies up to 90% until week 11 post-treatment, with a maximum efficacy of 98.3%, and significant differences were found between G-OXI and G-CON until the 26th week post-treatment. Closantel was insufficiently active (0–81%) throughout the study and differences compared to G-CON were never found. The present study reveals that oxyclozanide given at a single oral dose of 15 mg/kg BW is highly effective against adult rumen flukes in sheep. In addition, the use of a single oral dose of closantel at 10 mg/kg BW is not recommended for treating paramphistomid infections in sheep.
A review of fetal cardiac monitoring, with a focus on low- and middle-income countries

There is limited evidence regarding the utility of fetal monitoring during pregnancy, particularly during labor and delivery. Developed countries rely on consensus ‘best practices’ of obstetrics and gynecology professional societies to guide their protocols and policies. Protocols are often driven by the desire to be as safe as possible and avoid litigation, regardless of the cost of downstream treatment. In high-resource settings, there may be a justification for this approach. In low-resource settings, in particular, interventions can be costly and lead to adverse outcomes in subsequent pregnancies. Therefore, it is essential to consider the evidence and cost of different fetal monitoring approaches, particularly in the context of treatment and care in low-to-middle income countries. This article reviews the standard methods used for fetal monitoring, with particular emphasis on fetal cardiac assessment, which is a reliable indicator of fetal well-being. An overview of fetal monitoring practices in low-to-middle income counties, including perinatal care access challenges, is also presented. Finally, an overview of how mobile technology may help reduce barriers to perinatal care access in low-resource settings is provided.
Assessing Selectivity in the Basal Ganglia: The “Gearbox” Hypothesis

Despite experimental evidence, the literature so far contains no systematic attempt to address the impact of cortical oscillations on the ability of the basal ganglia (BG) to select. In this study, we employed a state-of-the-art spiking neural model of the BG circuitry and investigated the effectiveness of this circuitry as an action selection device. We found that cortical frequency, phase, dopamine and the examined time scale, all have a very important impact on this process. Our simulations resulted in a canonical profile of selectivity, termed selectivity portraits, which suggests that the cortex is the structure that determines whether selection will be performed in the BG and what strategy will be utilized. Some frequency ranges promote the exploitation of highly salient actions, others promote the exploration of alternative options, while the remaining frequencies halt the selection process. Based on this behaviour, we propose that the BG circuitry can be viewed as the “gearbox” of action selection. Coalitions of rhythmic cortical areas are able to switch between a repertoire of available BG modes which, in turn, change the course of information flow within the cortico-BG-thalamo-cortical loop. Dopamine, akin to “control pedals”, either stops or initiates a decision, while cortical frequencies, as a “gear lever”, determine whether a decision can be triggered and what type of decision this will be. Finally, we identified a selection cycle with a period of around 200ms, which was used to assess the biological plausibility of the popular cognitive architectures. Author summary Our brains are continuously called to select the most appropriate action between alternative competing choices. A plethora of evidence and theoretical work indicates that a fundamental brain region called the basal ganglia might be the locus where this competition occurs. But how is the winning choice determined each time? Using a detailed computational model, based on neurophysiological properties of this region, we suggest that, whereas the basal ganglia might indeed contain the circuitry of action selection, the cerebral cortex is, in fact, the brain region that dictates this process. Similarly to a gearbox in a car, the basal ganglia provide modes for the exploitation of the safest option (forward gears), exploration of alternative options (reverse gear) and a neutral state, in case that the selection process needs to be halted. Our results further indicate that the instructions for mode-switching are relayed to the basal ganglia through specific low frequencies of oscillations within cortical areas. Finally, we provide estimations for the frequency ranges that can be used to activate each selectivity mode, as well as the duration of the selection process under various conditions.