SARS-CoV-2 Rapid Antigen Test Based on a New Anti-Nucleocapsid Protein Monoclonal Antibody: Development and Real-Time Validation.

SARS-CoV-2 diagnostic tests have become an important tool for pandemic control. Among the alternatives for COVID-19 diagnosis, antigen rapid diagnostic tests (Ag-RDT) are very convenient and widely used. However, as SARS-CoV-2 variants may continuously emerge, the replacement of tests and reagents may be required to maintain the sensitivity of Ag-RDTs. Here, we describe the development and validation of an Ag-RDT during an outbreak of the Omicron variant, including the characterization of a new monoclonal antibody (anti-DTC-N 1B3 mAb) that recognizes the Nucleocapsid protein (N). The anti-DTC-N 1B3 mAb recognized the sequence TFPPTEPKKDKKK located at the C-terminus of the N protein of main SARS-CoV-2 variants of concern. Accordingly, the Ag-RDT prototypes using the anti-DTC-N 1B3 mAB detected all the SARS-CoV-2 variants-Wuhan, Alpha, Gamma, Delta, P2 and Omicron. The performance of the best prototype (sensitivity of 95.2% for samples with Ct ≤ 25; specificity of 98.3% and overall accuracy of 85.0%) met the WHO recommendations. Moreover, results from a patients' follow-up study indicated that, if performed within the first three days after onset of symptoms, the Ag-RDT displayed 100% sensitivity. Thus, the new mAb and the Ag-RDT developed herein may constitute alternative tools for COVID-19 point-of-care diagnosis and epidemiological surveillance.

Soft Tissue Benign Hand Masses in the First Web Space: A Retrospective Case Series.

INTRODUCTION: Hand masses are fairly common. While most of these masses are either ganglion cysts or benign tumors, masses in the first web space are not rare, and they may in fact represent a variety of lesions. These include both benign and malignant tumors, metastases, or congenital and anomalous structures, and may involve nerves, vascular structures, connective tissue, and joints. METHODS: In this retrospective case series, data on 12 cases of first dorsal web space hand mass treated at our center over a period of five years were collected and analyzed. RESULTS:  Twelve consecutive patients presenting with a first dorsal web space hand mass over a period of five years were reviewed. This represented a group of nine females and three males, with a mean age of 53 years (range = 16-70 years). Seven patients had a mass on the right side and five on the left side. The surgical approach to resect the mass in all 12 patients was dorsal. The most common diagnosis was ganglion cyst (50%), followed by lipoma (25%) and aneurysm (16.6%). There was one case of eccrine spiradenoma. CONCLUSION: First dorsal web space hand masses can encompass multiple different pathologies, and the first web space has an intricate anatomy. Both of these factors mandate a careful approach that includes meticulous preoperative planning with appropriate advanced imaging studies, which helps to make the surgical procedure more efficient and accurate.

There might be more to syntactic bootstrapping than being pragmatic: A look at grammatical person and prosody in naturalistic child-directed speech.

In 'Being pragmatic about syntactic bootstrapping', Hacquard (2022) argues that abstract syntax is useful for word learning, but that an additional cue, pragmatics, is both necessary and available for young children during the first steps of language acquisition. She focuses on modals and attitude verbs, where the physical context seems particularly impoverished as the sole basis for deriving meanings, and thus where linguistic cues may be particularly helpful. She convincingly shows how pragmatic and syntactic cues could be combined to help young language learners learn and infer the possible meanings of attitude verbs such as "think", "know" or "want". She also argues that, in some circumstances, syntax and pragmatics would need to be supplemented by semantic information from context - for instance, in the case of modals such as "might", "can", or "must". We agree with Hacquard on the importance of the synergies between these different cues to meaning, and wish to add two other aspects of the input that might also be used by young children in these contexts. The aspects we describe can only be noticed when one analyzes concrete examples of what children hear in their everyday lives, something which Hacquard does very often in her work (e.g., Dieuleveut, van Dooren, Cournane & Hacquard, 2022; Huang, White, Liao, Hacquard & Lidz, 2022; Yang, 2022). Taking into account different cues for meaning would help the field go beyond current models of syntactic bootstrapping, and create an integrated picture of the synergies between different levels of linguistic information.

Tracking the turnover of SARS-CoV-2 VOCs Gamma to Delta in a Brazilian state (Minas Gerais) with a high-vaccination status.

The emergence and global dissemination of Severe Acute Respiratory Syndrome virus 2 (SARS-CoV-2) variants of concern (VOCs) have been described as the main factor driving the Coronavirus Disease 2019 pandemic. In Brazil, the Gamma variant dominated the epidemiological scenario during the first period of 2021. Many Brazilian regions detected the Delta variant after its first description and documented its spread. To monitor the introduction and spread of VOC Delta, we performed Polymerase Chain Reaction (PCR) genotyping and genome sequencing in ten regional sentinel units from June to October 2021 in the State of Minas Gerais (MG). We documented the introduction and spread of Delta, comprising 70 per cent of the cases 8 weeks later. Comparing the viral loads of the Gamma and Delta dominance periods, we provide additional evidence that the latter is more transmissible. The spread and dominance of Delta did not culminate in the increase in cases and deaths, suggesting that the vaccination may have restrained the epidemic growth. Analysis of 224 novel Delta genomes revealed that Rio de Janeiro state was the primary source for disseminating this variant in the state of MG. We present the establishment of Delta, providing evidence of its enhanced transmissibility and showing that this variant shift did not aggravate the epidemiological scenario in a high immunity setting.

"The tiger is hitting! the duck too!" 3-year-olds can use prosodic information to constrain their interpretation of ellipsis.

This work aims to investigate French children's ability to use phrasal boundaries for disambiguation of a type of ambiguity not yet studied, namely stripping sentences versus simple transitive sentences. We used stripping sentences such as "[Le tigre tape]! [Le canard aussi]!" ("[The tiger is hitting]! [The duck too]!", in which both the tiger and the duck are hitting), which, without the prosodic information, would be ambiguous with a transitive sentence such as "[Le tigre] [tape le canard aussi]!" ("[The tiger] [is hitting the duck too]!", in which the tiger is hitting the duck). We presented 3-to-4-year-olds and 28-month-olds with one of the two types of sentence above, while they watched two videos side-by-side on a screen: one depicting the transitive interpretation of the sentences, and another depicting the stripping interpretation. The stripping interpretation video showed the two characters as agents of the named action (e.g. a duck and a tiger hitting a bunny), and the transitive interpretation video showed only the first character as an agent, and the second character as a patient of the action (e.g. the tiger hitting the duck and the bunny). The results showed that 3-to-4-year-olds use prosodic information to correctly distinguish stripping sentences from transitive sentences, as they looked significantly more at the appropriate video, while 28-month-olds show only a trend in the same direction. While recent studies demonstrated that from 18 months of age, infants are able to use phrasal prosody to guide the syntactic analysis of ambiguous sentences, our results show that only 3-to-4-year-olds were able to reliably use phrasal prosody to constrain the parsing of stripping sentences. We discuss several factors that can explain this delay, such as differences in the frequency of these structures in child-directed speech, as well as in the complexity of the sentences and of the experimental task. Our findings add to the growing body of evidence on the role of prosody in constraining parsing in young children.

"Look! It is not a bamoule!": 18- and 24-month-olds can use negative sentences to constrain their interpretation of novel word meanings.

Two word-learning experiments were conducted to investigate the understanding of negative sentences in 18- and 24-month-old children. In Experiment 1, after learning that bamoule means "penguin" and pirdaling means "cartwheeling," 18-month-olds (n = 48) increased their looking times when listening to negative sentences rendered false by their visual context ("Look! It is not a bamoule!" while watching a video showing a penguin cartwheeling); however, they did not change their looking behavior when negative sentences were rendered true by their context ("Look! It is not pirdaling!" while watching a penguin spinning). In Experiment 2, 24-month-olds (n = 48) were first exposed to a teaching phase in which they saw a new cartoon character on a television (e.g., a blue monster). Participants in the affirmative condition listened to sentences like "It's a bamoule!" and participants in the negative condition listened to sentences like "It's not a bamoule!." At test, all participants were asked to find the bamoule while viewing two images: the familiar character from the teaching phase versus a novel character (e.g., a red monster). Results showed that participants in the affirmative condition looked more to the familiar character (i.e., they learned the familiar character was a bamoule) than participants in the negative condition. Together, these studies provide the first evidence for the understanding of negative sentences during the second year of life. The ability to understand negative sentences so early might support language acquisition, providing infants with a tool to constrain the space of possibilities for word meanings.

Early use of nitazoxanide in mild COVID-19 disease: randomised, placebo-controlled trial.

BACKGROUND: Nitazoxanide is widely available and exerts broad-spectrum antiviral activity in vitro. However, there is no evidence of its impact on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: In a multicentre, randomised, double-blind, placebo-controlled trial, adult patients presenting up to 3 days after onset of coronavirus disease 2019 (COVID-19) symptoms (dry cough, fever and/or fatigue) were enrolled. After confirmation of SARS-CoV-2 infection using reverse transcriptase PCR on a nasopharyngeal swab, patients were randomised 1:1 to receive either nitazoxanide (500 mg) or placebo, three times daily, for 5 days. The primary outcome was complete resolution of symptoms. Secondary outcomes were viral load, laboratory tests, serum biomarkers of inflammation and hospitalisation rate. Adverse events were also assessed. RESULTS: From June 8 to August 20, 2020, 1575 patients were screened. Of these, 392 (198 placebo, 194 nitazoxanide) were analysed. Median (interquartile range) time from symptom onset to first dose of study drug was 5 (4-5) days. At the 5-day study visit, symptom resolution did not differ between the nitazoxanide and placebo arms. Swabs collected were negative for SARS-CoV-2 in 29.9% of patients in the nitazoxanide arm versus 18.2% in the placebo arm (p=0.009). Viral load was reduced after nitazoxanide compared to placebo (p=0.006). The percentage viral load reduction from onset to end of therapy was higher with nitazoxanide (55%) than placebo (45%) (p=0.013). Other secondary outcomes were not significantly different. No serious adverse events were observed. CONCLUSIONS: In patients with mild COVID-19, symptom resolution did not differ between nitazoxanide and placebo groups after 5 days of therapy. However, early nitazoxanide therapy was safe and reduced viral load significantly.

Toddlers exploit referential and syntactic cues to flexibly adapt their interpretation of novel verb meanings.

Because linguistic communication is often noisy and uncertain, adults flexibly rely on different information sources during sentence processing. We tested whether toddlers engage in a similar process and how that process interacts with verb learning. Across two experiments, we presented French 28-month-olds with right-dislocated sentences featuring a novel verb ("Hei is VERBing, the boyi"), where a clear prosodic boundary after the verb indicates that the sentence is intransitive (such that the NP "the boy" is coreferential with the pronoun "he" and the sentence means "The boy is VERBing"). By default, toddlers incorrectly interpreted the sentence based on the number of NPs (assuming, e.g., that someone is VERBing the boy). Yet, when children were provided with additional information about the syntactic contexts (Experiment 1, N = 81) or the referential/semantic content (Experiment 2, N = 72) of the novel verb, they successfully used the prosodic information as a cue to reach the correct syntactic structure of the sentence and infer the probable meaning of the novel verb. These results suggest that toddlers can flexibly adjust their interpretations of sentences depending on the reliability of the linguistic cues available. Thus, failure to parse a sentence in an adult-like fashion might not necessarily reflect the immaturity of children's parsing system but rather might be indicative of what cues children consider reliable in that context.

Familiar words can serve as a semantic seed for syntactic bootstrapping.

Young children can exploit the syntactic context of a novel word to narrow down its probable meaning. But how do they learn which contexts are linked to which semantic features in the first place? We investigate if 3- to 4-year-old children (n = 60) can learn about a syntactic context from tracking its use with only a few familiar words. After watching a 5-min training video in which a novel function word (i.e., 'ko') replaced either personal pronouns or articles, children were able to infer semantic properties for novel words co-occurring with the newly learned function word (i.e., objects vs. actions). These findings implicate a mechanism by which a distributional analysis, associated with a small vocabulary of known words, could be sufficient to identify some properties associated with specific syntactic contexts.

Effects of temperature changes in the transcriptional profile of the emerging fish pathogen Francisella noatunensis subsp. orientalis.

One of the major challenges in Nile tilapia (Oreochromis niloticus L.) farming is the occurrence of bacterial infections, and the Francisella noatunensis subsp. orientalis (FNO) is an important pathogen that has emerged in last decades. Francisellosis outbreaks have been reported in the literature as occurring seasonally when water temperature is below 24 °C. The aim of this study was to quantify the median lethal doses (LD50) of FNO in experimental challenges at 28 °C and 22 °C, and to investigate the impact of temperature changes in whole genome expression using microarray technology. The LD50 for Nile tilapia at 28 °C was ∼105.7, whereas at 22 °C, the LD50 was ∼102.2, showing that the decrease in temperature enhanced disease outcome. Out of 1917 genes screened, a total of 31 and 19 genes were down- and up-regulated at 22 °C, respectively. These genes were grouped by orthology into functional categories of: amino acid, inorganic ion, and carbohydrate transport and metabolism; transcription; and posttranslational modification, protein turnover, and chaperones. Expression of genes related to metabolism, oxidative stress, and thermal shock were regulated by temperature changes, reflecting an ability of FNO to adapt to the environment. Expression of virulence genes usually required for the Francisella genus was not changed between tested temperatures, including that of genes located on the Francisella Pathogenicity Island.

Studying the Real-Time Interpretation of Novel Noun and Verb Meanings in Young Children.

Decades of research show that children rely on the linguistic context in which novel words occur to infer their meanings. However, because learning in these studies was assessed after children had heard numerous occurrences of a novel word in informative linguistic contexts, it is impossible to determine how much exposure would be needed for a child to learn from such information. This study investigated the speed with which French 20-month-olds and 3-to-4-year-olds exploit function words to determine the syntactic category of novel words and therefore infer their meanings. In a real-time preferential looking task, participants saw two videos side-by-side on a TV-screen: one showing a person performing a novel action, and the other a person passively holding a novel object. At the same time, participants heard only three occurrences of a novel word preceded either by a determiner (e.g., "Regarde! Une dase! - "Look! A dase!") or a pronoun (e.g., "Regarde! Elle dase!" - "Look! She's dasing!"). 3-to-4-year-olds exploited function words to categorize novel words and infer their meanings: they looked more to the novel action in the verb condition, while participants in the noun condition looked more to the novel object. 20-month-olds, however, did not show this difference. We discuss possible reasons for why 20-month-olds may have found it difficult to infer novel word meanings in our task. Given that 20-month-olds can use function words to learn word meanings in experiments providing many repetitions, we suspect that more repetitions might be needed to observe positive effects of learning in this age range in our task. Our study establishes nevertheless that before age 4, young children become able to exploit function words to infer the meanings of unknown words as soon as they occur. This ability to interpret speech in real-time and build interpretations about novel word meanings might be extremely useful for young children to map words to their possible referents and to boost their acquisition of word meanings.

Prosody and Function Words Cue the Acquisition of Word Meanings in 18-Month-Old Infants.

Language acquisition presents a formidable task for infants, for whom word learning is a crucial yet challenging step. Syntax (the rules for combining words into sentences) has been robustly shown to be a cue to word meaning. But how can infants access syntactic information when they are still acquiring the meanings of words? We investigated the contribution of two cues that may help infants break into the syntax and give a boost to their lexical acquisition: phrasal prosody (speech melody) and function words, both of which are accessible early in life and correlate with syntactic structure in the world's languages. We show that 18-month-old infants use prosody and function words to recover sentences' syntactic structure, which in turn constrains the possible meanings of novel words: Participants ( N = 48 in each of two experiments) interpreted a novel word as referring to either an object or an action, given its position within the prosodic-syntactic structure of sentences.

Three- to Four-Year-Old Children Rapidly Adapt Their Predictions and Use Them to Learn Novel Word Meanings.

Adults create and update predictions about what speakers will say next. This study asks whether prediction can drive language acquisition, by testing whether 3- to 4-year-old children (n = 45) adapt to recent information when learning novel words. The study used a syntactic context which can precede both nouns and verbs to manipulate children's predictions about what syntactic category will follow. Children for whom the syntactic context predicted verbs were more likely to infer that a novel word appearing in this context referred to an action, than children for whom it predicted nouns. This suggests that children make rapid changes to their predictions, and use this information to learn novel information, supporting the role of prediction in language acquisition.

Complete genome sequencing of sixteen Francisella noatunensis subsp. orientalis isolates: A genomic approach for molecular characterization and spread dynamics of this clonal population.

Francisella noatunensis subsp. orientalis (FNO) is an important emerging pathogen associated with disease outbreaks in farm-raised Nile tilapia. FNO genetic diversity using PCR-based typing, no intra-species discrimination was achieved among isolates/strains from different countries, thus demonstrating a clonal behaviour pattern. In this study, we aimed to evaluate the population structure of FNO isolates by comparing whole-genome sequencing data. The analysis of recombination showed that Brazilian isolates group formed a clonal population; whereas other lineages are also supported by this analysis for isolates from foreign countries. The whole-genome multilocus sequence typing (wgMLST) analysis showed varying numbers of dissimilar alleles, suggesting that the Brazilian clonal population are in expansion. Each Brazilian isolate could be identified as a single node by high-resolution gene-by-gene approach, presenting slight genetic differences associated to mutational events. The common ancestry node suggests a single entry into the country before 2012, and the rapid dissemination of this infectious agent may be linked to market sales of infected fingerlings.

Phrasal prosody constrains syntactic analysis in toddlers.

This study examined whether phrasal prosody can impact toddlers' syntactic analysis. French noun-verb homophones were used to create locally ambiguous test sentences (e.g., using the homophone as a noun: [le bébésouris] [a bien mangé] - [the baby mouse] [ate well] or using it as a verb: [le bébé] [sourità sa maman] - [the baby] [smiles to his mother], where brackets indicate prosodic phrase boundaries). Although both sentences start with the same words (le-bebe-/suʁi/), they can be disambiguated by the prosodic boundary that either directly precedes the critical word /suʁi/ when it is a verb, or directly follows it when it is a noun. Across two experiments using an intermodal preferential looking procedure, 28-month-olds (Exp. 1 and 2) and 20-month-olds (Exp. 2) listened to the beginnings of these test sentences while watching two images displayed side-by-side on a TV-screen: one associated with the noun interpretation of the ambiguous word (e.g., a mouse) and the other with the verb interpretation (e.g., a baby smiling). The results show that upon hearing the first words of these sentences, toddlers were able to correctly exploit prosodic information to access the syntactic structure of sentences, which in turn helped them to determine the syntactic category of the ambiguous word and to correctly identify its intended meaning: participants switched their eye-gaze toward the correct image based on the prosodic condition in which they heard the ambiguous target word. This provides evidence that during the first steps of language acquisition, toddlers are already able to exploit the prosodic structure of sentences to recover their syntactic structure and predict the syntactic category of upcoming words, an ability which would be extremely useful to discover the meaning of novel words.

Ambiguous function words do not prevent 18-month-olds from building accurate syntactic category expectations: An ERP study.

To comprehend language, listeners need to encode the relationship between words within sentences. This entails categorizing words into their appropriate word classes. Function words, consistently preceding words from specific categories (e.g., the ballNOUN, I speakVERB), provide invaluable information for this task, and children's sensitivity to such adjacent relationships develops early on in life. However, neighboring words are not the sole source of information regarding an item's word class. Here we examine whether young children also take into account preceding sentence context online during syntactic categorization. To address this question, we use the ambiguous French function word la which, depending on sentence context, can either be used as determiner (the, preceding nouns) or as object clitic (it, preceding verbs). French-learning 18-month-olds' evoked potentials (ERPs) were recorded while they listened to sentences featuring this ambiguous function word followed by either a noun or a verb (thus yielding a locally felicitous co-occurrence of la + noun or la + verb). Crucially, preceding sentence context rendered the sentence either grammatical or ungrammatical. Ungrammatical sentences elicited a late positivity (resembling a P600) that was not observed for grammatical sentences. Toddlers' analysis of the unfolding sentence was thus not limited to local co-occurrences, but rather took into account non-adjacent sentence context. These findings suggest that by 18 months of age, online word categorization is already surprisingly robust. This could be greatly beneficial for the acquisition of novel words.

Scalar Implicatures: The Psychological Reality of Scales.

Scalar implicatures, the phenomena where a sentence like "The pianist played some Mozart sonatas" is interpreted, as "The pianist did not play all Mozart sonatas" have been given two different analyses. Neo-Griceans (NG) claim that this interpretation is based on lexical scales (e.g., ), where the stronger term (e.g., all) implies the weaker term (e.g., some), but the weaker term (e.g., some) implicates the negation of the stronger term (i.e., some = not all). Post-Griceans (PG) deny that this is the case and offer a context-based inferential account for scalar implicatures. While scalar implicatures have been extensively investigated, with results apparently in favor of PG accounts, the psychological reality of lexical scales has not been put to the test. This is what we have done in the present experiment, with a lexical decision task using lexical scales in a masked priming paradigm. While PG accounts do not attribute any role for lexical scales in the computation of scalar implicatures, NG accounts suggest that lexical scales are the core mechanism behind the computation of scalar implicatures, and predict that weaker terms in a scale should prime stronger terms more than the reverse because stronger words are necessary to the interpretation of weaker words, while stronger words can be interpreted independently of weaker words. Our results provided evidence in favor of the psychological existence of scales, leading to the first clear experimental support for the NG account.

English-speaking preschoolers can use phrasal prosody for syntactic parsing.

This study tested American preschoolers' ability to use phrasal prosody to constrain their syntactic analysis of locally ambiguous sentences containing noun/verb homophones (e.g., [The baby flies] [hide in the shadows] vs [The baby] [flies his kite], brackets indicate prosodic boundaries). The words following the homophone were masked, such that prosodic cues were the only disambiguating information. In an oral completion task, 4- to 5-year-olds successfully exploited the sentence's prosodic structure to assign the appropriate syntactic category to the target word, mirroring previous results in French (but challenging previous English-language results) and providing cross-linguistic evidence for the role of phrasal prosody in children's syntactic analysis.

A MLST Clade 2 Clostridium difficile strain with a variant TcdB induces severe inflammatory and oxidative response associated with mucosal disruption.

The epidemiology of Clostridium difficile infections is highly dynamic as new strains continue to emerge worldwide. Here we present a detailed analysis of a new C. difficile strain (ICC-45) recovered from a cancer patient in Brazil that died from severe diarrhea. A polyphasic approach assigned a new PCR-ribotype and PFGE macrorestriction pattern to strain ICC-45, which is toxigenic (tcdA(+), tcdB(+) and ctdB(+)) and classified as ST41 from MLST Clade 2 and toxinotype IXb. Strain ICC-45 encodes for a variant TcdB that induces a distinct CPE in agreement with its toxinotype. Unlike epidemic NAP1/027 strains, which are also classified to MLST Clade 2, strain ICC-45 is susceptible to fluoroquinolones and does not overproduce toxins TcdA and TcdB. However, supernatants from strain ICC-45 and a NAP1/027 strain produced similar expression of pro-inflammatory cytokines, epithelial damage, and oxidative stress response in the mouse ileal loop model. These results highlight inflammation and oxidative stress as common features in the pathogenesis of C. difficile Clade 2 strains. Finally, this work contributes to the description of differences in virulence among various C. difficile strains.

Complete genome sequence of Streptococcus agalactiae strain GBS85147 serotype of type Ia isolated from human oropharynx.

Streptococcus agalactiae, also referred to as Group B Streptococcus, is a frequent resident of the rectovaginal tract in humans, and a major cause of neonatal infection. The pathogen can also infect adults with underlying disease, particularly the elderly and immunocompromised ones. In addition, S. agalactiae is a known fish pathogen, which compromises food safety and represents a zoonotic hazard. This study provides valuable structural, functional and evolutionary genomic information of a human S. agalactiae serotype Ia (ST-103) GBS85147 strain isolated from the oropharynx of an adult patient from Rio de Janeiro, thereby representing the first human isolate in Brazil. We used the Ion Torrent PGM platform with the 200 bp fragment library sequencing kit. The sequencing generated 578,082,183 bp, distributed among 2,973,022 reads, resulting in an approximately 246-fold mean coverage depth and was assembled using the Mira Assembler v3.9.18. The S. agalactiae strain GBS85147 comprises of a circular chromosome with a final genome length of 1,996,151 bp containing 1,915 protein-coding genes, 18 rRNA, 63 tRNA, 2 pseudogenes and a G + C content of 35.48 %.