Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhancement of speech-in-noise comprehension through vibrotactile stimulation at the syllabic rate

Significance Syllables are important building blocks of speech. They occur at a rate between 4 and 8 Hz, corresponding to the theta frequency range of neural activity in the cerebral cortex. When listening to speech, the theta activity becomes aligned to the syllabic rhythm, presumably aiding in parsing a speech signal into distinct syllables. However, this neural activity cannot only be influenced by sound, but also by somatosensory information. Here, we show that the presentation of vibrotactile signals at the syllabic rate can enhance the comprehension of speech in background noise. We further provide evidence that this multisensory enhancement of speech comprehension reflects the multisensory integration of auditory and tactile information in the auditory cortex.
Adipose tissue provides a cushioning effect in low-energy isolated blunt thoracic trauma: a prospective observational study

Abstract Introduction This study aimed to investigate the specific effects of subcutaneous adipose tissue thickness (SATT) on trauma-related injury (TRI) development in patients with low-energy isolated blunt thoracic trauma. Patients and Methods This prospective observational study was performed between March 2018–March 2019. Patients admitted to our hospital because of blunt thoracic trauma were enrolled. SATT in axial CT images of the thorax was measured using the four anatomically designated localizations. Patients were analyzed in terms of demographic data, BMI, comorbid diseases, causes of injury, vital parameters, visual analog scale, trauma score, injury type, treatment, and hospitalization. A poor clinical outcome was defined as the development of a TRI. Results The study group consisted of 152 patients (43 female, 109 male). The mean age was 49 ± 19.1 years. There was a positive linear association between the BMI and SATT for all the patients in the study. TRI frequency was higher in the low-SATT subgroup than in the high-SATT group (p < 0.001). BMI and mean SATT values were related to a poor logistic regression analysis outcome (p < 0.01). Being in the low-BMI subgroup was a risk factor for TRI development (p < 0.01; OR:0.23;95% CI:0.08–0.61). Conclusion We found that a low SATT and BMI were related to a poor clinical outcome in our study group. It is essential to carefully examine these patients in detail, even in low-energy trauma. Subcutaneous tissue over the thorax serves as a protective shield for other thoracic structures in patients with LEBTT.
Mining the Flavoproteome of Brucella ovis, the Brucellosis Causing Agent in Ovis aries

Some microorganisms depend heavily on flavin-dependent activities, but others maintain them at a minimum. Knowledge about flavoprotein content and functions in different microorganisms will help to identify their metabolic requirements, as well as to benefit either industry or health. ABSTRACT Flavoproteins are a diverse class of proteins that are mostly enzymes and contain as cofactors flavin mononucleotide (FMN) and/or flavin adenine dinucleotide (FAD), which enable them to participate in a wide range of physiological reactions. We have compiled 78 potential proteins building the flavoproteome of Brucella ovis (B. ovis), the causative agent of ovine brucellosis. The curated list of flavoproteins here reported is based on (i) the analysis of sequence, structure and function of homologous proteins, and their classification according to their structural domains, clans, and expected enzymatic functions; (ii) the constructed phylogenetic trees of enzyme functional classes using 19 Brucella strains and 26 pathogenic and/or biotechnological relevant alphaproteobacteria together with B. ovis; and (iii) the evaluation of the genetic context for each entry. Candidates account for ∼2.7% of the B. ovis proteome, and 75% of them use FAD as cofactor. Only 55% of these flavoproteins belong to the core proteome of Brucella and contribute to B. ovis processes involved in maintenance activities, survival and response to stress, virulence, and/or infectivity. Several of the predicted flavoproteins are highly divergent in Brucella genus from revised proteins and for them it is difficult to envisage a clear function. This might indicate modified catalytic activities or even divergent processes and mechanisms still not identified. We have also detected the lack of some functional flavoenzymes in B. ovis, which might contribute to it being nonzoonotic. Finally, potentiality of B. ovis flavoproteome as the source of antimicrobial targets or biocatalyst is discussed. IMPORTANCE Some microorganisms depend heavily on flavin-dependent activities, but others maintain them at a minimum. Knowledge about flavoprotein content and functions in different microorganisms will help to identify their metabolic requirements, as well as to benefit either industry or health. Currently, most flavoproteins from the sheep pathogen Brucella ovis are only automatically annotated in databases, and only two have been experimentally studied. Indeed, certain homologues with unknown function are not characterized, and they might relate to still not identified mechanisms or processes. Our research has identified 78 members that comprise its flavoproteome, 76 of them flavoenzymes, which mainly relate to bacteria survival, virulence, and/or infectivity. The list of flavoproteins here presented allows us to better understand the peculiarities of Brucella ovis and can be applied as a tool to search for candidates as new biocatalyst or antimicrobial targets.
Rituximab Therapy in the Treatment of Juvenile Myasthenia Gravis

Background and Objectives Corticosteroids are the first-line immunosuppressants in the management of juvenile myasthenia gravis despite their adverse effects. The place of new immunosuppressive therapies is not clearly defined by the last international consensus held in March 2019 due to the lack of clinical trials. The aim of this study is to describe the use of rituximab and its efficacy and safety in 8 main pediatric centers of the French neuromuscular reference network to propose a new place in the therapeutic strategy of juvenile myasthenia gravis. Methods We conducted a retrospective multicenter study from January 1, 2009, to April 30, 2020, including a large cohort of children with myasthenia gravis in 8 main French pediatric reference centers of the FILNEMUS network. The type of myasthenia, different lines of immunosuppressive treatment, and clinical course of the patients were collected. To evaluate the efficacy of rituximab, we studied the clinical course of patients on immunosuppressive therapy. Outcome was defined as the clinical and therapeutic status of patients at the last visit: stable without immunosuppressants, stable with immunosuppressants, or unstable. Results We included 74 patients: 18 children with ocular form and 56 children with generalized form. Of the 37 patients who required immunosuppressive therapy, 27 were treated with rituximab. Patients treated with rituximab had a better outcome than patients treated with conventional immunosuppressants (p = 0.006). The use of rituximab as a first-line immunosuppressant showed a better efficacy with a discontinuation of immunosuppressants in 75% of patients (vs 25%, p = 0.04) and results in cortisone sparing (42% vs 92%, p = 0.03) compared with rituximab treatment as a second- or third-line immunosuppression. Rituximab was well tolerated; no adverse effect was observed. Discussion The use of rituximab has increased in France over the last 10 years as a first-line immunosuppressant. This study suggests good tolerability and efficacy of rituximab in juvenile myasthenia gravis. Early use appears to improve outcomes and facilitate cortisone sparing in antibody-positive generalized juvenile myasthenia. Classification of Evidence This study provides Class III evidence that for children with MG, rituximab is effective and well tolerated.
Stretch-Induced Healing of Injured Muscles Is Associated With Myogenesis and Decreased Fibrosis

Background: Alghouth therapeutic stretching exercise has been applied to accelerate the healing of injured skeletal muscles, mechanisms behind the mechanical stretch-induced muscle recovery remain unclear. Purpose: To examine stretch-associated antifibrotic and myogenic responses in injured muscles and to evaluate the feasibility of the ultrasonic Nakagami parametric index (NPI) in assessing muscle morphology during recovery. Study Design: Controlled laboratory study. Methods: Skeletal muscle fibrosis was induced in the right hind legs of 48 rats by making a posterior transverse incision in the gastrocnemius muscle; the left hind legs remained intact as a comparative normal reference. After surgery, the 48 rats were randomly divided into the stretch (S) and control (C) groups. The S group received stretching interventions on the injured hind leg from week 3 to week 7 after surgery, while the C group did not receive stretching throughout the study period. The muscle fibrosis percentage and the ultrasonic NPI were examined sequentially after surgery. Relative expressions of myogenesis-related proteins, including myoblast determination protein 1 (MyoD), myogenin, and embryonic myosin heavy chain (MHCemb), were also evaluated during the follow-up. Results: Mean fibrosis percentages in the injured hind leg were approximately 25% at week 3 in both groups, but they were significantly decreased by approximately 20% from week 4 to the end of the follow-up in the S group only (all, P < .05). Upon injury, the NPI values of injured hind legs in both groups dramatically dropped. Within the S group, stretching increased the NPI values of injured hind legs, which approached those of control hind legs at weeks 6 and 7. The highest MyoD, myogenin, and MHCemb levels were observed at week 6 in both groups. The NPI values corresponded to the MyoD expression in the S group during the follow-up. Conclusion: Stretching induced a decrease in muscle fibrosis and an increase in myogenesis in injured muscles. The NPI values correspond to the myogenesis process. Clinical Relevance: The NPI may be capable of continuously monitoring the injured skeletal muscle morphology during the healing process in clinical settings.
Risk for Acute Myocardial Infarction After Ophthalmologic Procedures

BACKGROUND Preoperative cardiovascular evaluations are frequently done before ambulatory ophthalmologic procedures. However, whether these procedures can trigger an acute myocardial infarction (AMI) is unknown. OBJECTIVE To assess the short-term risk for AMI associated with ophthalmologic procedures. DESIGN Case-crossover design. SETTING Population-based nationwide study from Norway and Sweden. PARTICIPANTS First-time patients with AMI, aged 40 years and older, identified via inpatient registries and linked to outpatient surgical procedures in Norway (2008 to 2014) and Sweden (2001 to 2014), respectively. MEASUREMENTS Using self-matching, for each participant, exposure to ophthalmologic procedures in the 0 to 7 days before AMI diagnosis (hazard period) was compared with an 8-day period 30 days earlier, that is, days 29 to 36 before AMI (control period) to estimate the relative risk for an AMI the week after an ophthalmologic procedure. The odds ratios (ORs) with 95% CIs were calculated, using conditional logistic regression. Only patients who had a procedure of interest during either the hazard or control period were included. RESULTS For the 806 patients with AMI included in this study, there was a lower likelihood of AMI in the week after an ophthalmologic procedure than during the control week (OR, 0.83; 95% CI, 0.75 to 0.91). Furthermore, there was no evidence of increased risk for AMI when analyses were stratified by surgery subtype, anesthesia (local or general), duration, invasiveness (low, intermediate, or high), patient's age (<65 years or ≥65 years), or comorbidity (none vs. any). LIMITATION Potential bias from time-varying confounders between the hazard and the control periods. CONCLUSION Ophthalmologic procedures done in an outpatient setting did not seem to be associated with an increased risk for AMI. PRIMARY FUNDING SOURCE Central Norway Regional Health Authority and the Swedish Research Council.
Unique characteristics of tertiary lymphoid structures in kidney clear cell carcinoma: prognostic outcome and comparison with bladder cancer

Background The aims of this study were (1) to clarify the impact of tertiary lymphoid structure (TLS) status on the outcome and immunogenomic profile of human clear cell renal cell carcinoma (ccRCC) and (2) to determine phenotypic differences in TLSs between different types of genitourinary cancer, that is, urinary ccRCC and bladder cancer. Methods We performed a quantitative immunohistological analysis of ccRCC tissue microarrays and conducted integrated genome mutation analysis by next-generation sequencing and methylation array analysis. Since the tumor immune microenvironment of ccRCC often differs from that of other cancer types, we analyzed the phenotypic differences in TLSs between ccRCC and in-house bladder cancer specimens. Results Varying distribution patterns of TLSs were observed throughout ccRCC tumors, revealing that the presence of TLSs was related to poor prognosis. An analysis of genomic alterations based on TLS status in ccRCC revealed that alterations in the PI3K-mTOR pathway were highly prevalent in TLS-positive tumors. DNA methylation profiling also revealed distinct differences in methylation signatures among ccRCC samples with different TLS statuses. However, the TLS characteristics of ccRCC and bladder cancer markedly differed: TLSs had the exact opposite prognostic impact on bladder cancer as on ccRCC. The maturity and spatial distribution of TLSs were significantly different between the two cancer types; TLSs were more mature with follicle-like germinal center organization and likely to be observed inside the tumor in bladder cancer. Labeling for CD8, FOXP3, PD-1, and PD-L1 showed marked differences in the diversity of the immune microenvironment surrounding TLSs. The proportions of CD8-, FOXP3-, and PD-L1-positive cells were significantly higher in TLSs in bladder cancer than in TLSs in ccRCC; rather the proportion of PD-1-positive cells was significantly higher in TLSs in ccRCC than in TLSs in bladder cancer. Conclusion The immunobiology of ccRCC is unique, and various cancerous phenomena conflict with that seen in other cancer types; therefore, comparing the TLS characteristics between ccRCC and bladder cancer may help reveal differences in the prognostic impact, maturity and spatial distribution of TLSs and in the immune environment surrounding TLSs between the two cancers.
BmPMFBP1 regulates the development of eupyrene sperm in the silkworm, Bombyx mori

Sperm deliver the male complement of DNA to the ovum, and thus play a key role in sexual reproduction. Accordingly, spermatogenesis has outstanding significance in fields as disparate as infertility treatments and pest-control, making it a broadly interesting and important focus for molecular genetics research in a wide range of species. Here we investigate spermatogenesis in the model lepidopteran insect Bombyx mori (silkworm moth), with particular focus on the gene PMFBP1 (polyamine modulated factor 1 binding protein 1). In humans and mouse, PMFBP1 is essential for spermatogenesis, and mutations of this gene are associated with acephalic spermatozoa, which cause infertility. We identified a B. mori gene labeled as “PMFBP1” in GenBank’s RefSeq database and sought to assess its role in spermatogenesis. Like in mammals, the silkworm version of this gene (BmPMFBP1) is specifically expressed in testes. We subsequently generated BmPMFBP1 mutants using a transgenic CRISPR/Cas9 system. Mutant males were sterile while the fertility of mutant females was comparable to wildtype females. In B. mori, spermatogenesis yields two types of sperm, the nucleated fertile eupyrene sperm, and anucleated unfertile apyrene sperm. Mutant males produced abnormal eupyrene sperm bundles but normal apyrene sperm bundles. For eupyrene sperm, nuclei were mislocated and disordered inside the bundles. We also found the BmPMFBP1 deficiency blocked the release of eupyrene sperm bundles from testes to ejaculatory seminalis. We found no obvious abnormalities in the production of apyrene sperm in mutant males, and double-matings with apyrene-deficient sex-lethal mutants rescued the ΔBmPMFBP1 infertility phenotype. These results indicate BmPMFBP1 functions only in eupyrene spermatogenesis, and highlight that distinct genes underlie the development of the two sperm morphs commonly found in Lepidoptera. Bioinformatic analyses suggest PMFBP1 may have evolved independently in lepidoptera and mammals, and that despite the shared name, are likely not homologous genes.
Impact of Acquired Broad-Spectrum β-Lactamases on Susceptibility to Cefiderocol and Newly Developed β-Lactam/β-Lactamase Inhibitor Combinations in Escherichia coli and Pseudomonas aeruginosa

The ability of broad-spectrum β-lactamases to reduce the susceptibility to ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), imipenem-relebactam, meropenem-vaborbactam, aztreonam-avibactam (AZA), and cefiderocol (FDC) was evaluated both in Pseudomonas aeruginosa and in Escherichia coli using isogenic backgrounds. Although metallo-β-lactamases conferred resistance in most cases, except for AZA, several clavulanic-acid-inhibited extended-spectrum β-lactamases (PER, BEL, SHV) had a significant impact on the susceptibility to CZA, C/T, and FDC. ABSTRACT The ability of broad-spectrum β-lactamases to reduce the susceptibility to ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), imipenem-relebactam, meropenem-vaborbactam, aztreonam-avibactam (AZA), and cefiderocol (FDC) was evaluated both in Pseudomonas aeruginosa and in Escherichia coli using isogenic backgrounds. Although metallo-β-lactamases conferred resistance in most cases, except for AZA, several clavulanic-acid-inhibited extended-spectrum β-lactamases (PER, BEL, SHV) had a significant impact on the susceptibility to CZA, C/T, and FDC.
Global evidence of persistent violations of the International Code of Marketing of Breast‐milk Substitutes: A systematic scoping review

Abstract The influence of marketing on infant and young child feeding and health is well recognized, and an International Code was adopted by the World Health Assembly (WHA) in 1981 to reduce inappropriate marketing and protect breastfeeding. Yet the marketing and influencing continue. This scoping review systematically examined the published research evidence on the nature and extent of exposure to International Code violations from 1981 to August 2021. We used several search strategies involving multi‐language databases, organization websites, citation tracking, and expert consultation, to find research items meeting our inclusion criteria. We evaluated 657 items and retained 153 studies from at least 95 countries in the review. The majority of the studies (n = 113) documenting exposure to inappropriate marketing were published since 2010. Studies reported a broad range of marketing violations targeting mothers and families, health workers, and the general public. Marketing via digital platforms and brand extension has become more frequent. The evidence shows the use of misleading and inaccurate labeling and health and nutrition claims in breach of the Code. Our review confirms that violations of the Code have not ceased and calls for renewed attention from the WHA and national governments to protect the health of children and their mothers.
Parasite powerhouse: A review of the Toxoplasma gondii mitochondrion

Toxoplasma gondii is a member of the apicomplexan phylum, a group of single‐celled eukaryotic parasites that cause significant human morbidity and mortality around the world. T. gondii harbors two organelles of endosymbiotic origin: a non‐photosynthetic plastid, known as the apicoplast, and a single mitochondrion derived from the ancient engulfment of an α‐proteobacterium. Due to excitement surrounding the novelty of the apicoplast, the T. gondii mitochondrion was, to a certain extent, overlooked for about two decades. However, recent work has illustrated that the mitochondrion is an essential hub of apicomplexan‐specific biology. Development of novel techniques, such as cryo‐electron microscopy, complexome profiling, and next‐generation sequencing have led to a renaissance in mitochondrial studies. This review will cover what is currently known about key features of the T. gondii mitochondrion, ranging from its genome to protein import machinery and biochemical pathways. Particular focus will be given to mitochondrial features that diverge significantly from the mammalian host, along with discussion of this important organelle as a drug target.
Towards evidence‐based conservation of subterranean ecosystems

Subterranean ecosystems are among the most widespread environments on Earth, yet we still have poor knowledge of their biodiversity. To raise awareness of subterranean ecosystems, the essential services they provide, and their unique conservation challenges, 2021 and 2022 were designated International Years of Caves and Karst. As these ecosystems have traditionally been overlooked in global conservation agendas and multilateral agreements, a quantitative assessment of solution‐based approaches to safeguard subterranean biota and associated habitats is timely. This assessment allows researchers and practitioners to understand the progress made and research needs in subterranean ecology and management. We conducted a systematic review of peer‐reviewed and grey literature focused on subterranean ecosystems globally (terrestrial, freshwater, and saltwater systems), to quantify the available evidence‐base for the effectiveness of conservation interventions. We selected 708 publications from the years 1964 to 2021 that discussed, recommended, or implemented 1,954 conservation interventions in subterranean ecosystems. We noted a steep increase in the number of studies from the 2000s while, surprisingly, the proportion of studies quantifying the impact of conservation interventions has steadily and significantly decreased in recent years. The effectiveness of 31% of conservation interventions has been tested statistically. We further highlight that 64% of the reported research occurred in the Palearctic and Nearctic biogeographic regions. Assessments of the effectiveness of conservation interventions were heavily biased towards indirect measures (monitoring and risk assessment), a limited sample of organisms (mostly arthropods and bats), and more accessible systems (terrestrial caves). Our results indicate that most conservation science in the field of subterranean biology does not apply a rigorous quantitative approach, resulting in sparse evidence for the effectiveness of interventions. This raises the important question of how to make conservation efforts more feasible to implement, cost‐effective, and long‐lasting. Although there is no single remedy, we propose a suite of potential solutions to focus our efforts better towards increasing statistical testing and stress the importance of standardising study reporting to facilitate meta‐analytical exercises. We also provide a database summarising the available literature, which will help to build quantitative knowledge about interventions likely to yield the greatest impacts depending upon the subterranean species and habitats of interest. We view this as a starting point to shift away from the widespread tendency of recommending conservation interventions based on anecdotal and expert‐based information rather than scientific evidence, without quantitatively testing their effectiveness.