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Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015. Since its conception, MIBiG has been regularly updated to expand data coverage and remain up to date with innovations in natural product research. Here, we describe MIBiG version 4.0, an extensive update to the data repository and the underlying data standard. In a massive community annotation effort, 267 contributors performed 8304 edits, creating 557 new entries and modifying 590 existing entries, resulting in a new total of 3059 curated entries in MIBiG. Particular attention was paid to ensuring high data quality, with automated data validation using a newly developed custom submission portal prototype, paired with a novel peer-reviewing model. MIBiG 4.0 also takes steps towards a rolling release model and a broader involvement of the scientific community. MIBiG 4.0 is accessible online at https://mibig.secondarymetabolites.org/.

Introduction: Genetic polymorphisms who disturb the mineral homeostasis during tooth development and eruption are candidate to clarify the molecular mechanisms involved in changes in the tooth eruption chronology. In this study, we evaluate whether the FokI (rs2228570) and BglI (rs739837) polymorphisms in the Vitamin D receptor (VDR) gene are associated with changes in the chronology of eruption of permanent teeth. Material & method: This cross-sectional study randomly included 353 biologically unrelated children, both sexes, without systemic impairment or syndromes and history of trauma during the primary dentition. One operator perform the oral clinical examination. The tooth was considered erupted if there was a visible minimum of any tooth surface emerging from the mucosa. Genomic DNA was extracted from buccal epithelial cells from saliva samples. Genotyping was performed by Real-Time Polymerase Chain Reactions using TaqMan® technology. The average of the total number of erupted permanent teeth between the genotypes was compared by the Mann-Whitney test and multivariate Generalized Linear Models (GLM) (α = 5 %). β values with Confidence Interval (CI) 95 % were calculated. Results: The heterozygous adenine-guanine genotype of the FokI significantly decreases the number of erupted permanent teeth (β = −1.15; CI 95 % = −2.22 to −0.07; p = 0.036). In the stratified analysis for maxillary and mandibular teeth, this genotype was associated with a decrease in the number of erupted maxillary permanent teeth (β = −0.65; CI 95 % = −1.22 to −0.09; p = 0.023). BglI was not associated with permanent teeth eruption. Conclusion: The FokI, but not BglI, in the VDR may delay the eruption of permanent teeth.

Objective: To evaluate the color stability, surface roughness, and microhardness of resin-based composites (RBCs) after accelerated artificial aging (AAA) or immersion in beverages consumed by children. Material and Methods: Seventy specimens were prepared from each RBC (Z350-Z350, SS-Spectra Smart, AF-Admira Fusion, and EA-Estelite Asteria). Initial color, ∆E00, surface roughness, ∆Ra, and microhardness, ∆KHN readings were done. Specimens were separated into five groups (n=14): AAA (300 hours) and immersion (30 minutes daily/30 days) in Coca-Cola (CC), Grape juice (GJ), Chocolate milk (CM), or distilled water (DW). After the final readings, color and microhardness data were analyzed using two-way ANOVA, Tukey, and surface roughness by Kruskal-Wallis and Dunn's test. Results: SS exhibited the most significant color change in AAA, which differed from CC and GJ; the minor change occurred after CM and DW, which were distinct from each other. AF did not show a difference between the treatments. All RBCs exhibited a decrease in microhardness, except for SS, after AAA and EA in CC and DW. There was no difference in the surface roughness after treatments, except for AAA, which presented a minor change for Z350 and AF, differing from the other treatments. Conclusion: The beverages didn’t alter the surface roughness but decreased the microhardness of the RBCs, except for CC, which increased the microhardness of EA.

Arctic regions are among the fastest warming areas of the planet. Increasing average temperatures over the last five decades have deepened the thawing of the upper-most layer of permafrost across the Arctic, which contains significant amounts of organic carbon. The progressive deepening of seasonal thawing releases carbon that is used by active microorganisms which also produce greenhouse gases, potentially onsetting a positive feedback on global warming. Despite their importance in controlling organic matter degradation and greenhouse gas fluxes to the atmosphere, there is a lack of data on activity and dynamics of microbial communities in High Arctic soils in response to seasonal thaw. This report describes three specific expeditions performed on the Svalbard archipelago, carried out within the framework of the PRA (Italian Arctic Research Program) project Melting-ICE, performed between February and October 2022, reporting site characteristics and samples collected. The project aims to investigate the diversity and activity of active layer microbial communities across a full season thaw cycle, correlating microbial diversity with gas fluxes and composition. During these expeditions, a total of eight different sites were selected to investigate the microbiology and geochemistry of soils, as well as to estimate the gas fluxes from the soil to the atmosphere. The data collected in the field, combined with the results obtained in the laboratory, will provide a snapshot of the seasonal activity of the microbial communities present in the permafrost’s active layer. The three campaigns will provide data to estimate the impact of permafrost melting on the carbon cycle and the role of microorganisms in the release of greenhouse gases.

Despite native whey (hereafter termed WHEY) being a watery by-product rich in high-value nutritional components, it poses environmental concerns. Recently, the techniques of thermal-mechanical microparticulation to produce microparticulated whey (MPW) and a further process to ferment MPW (FMPW) were suggested, in order to recycle whey into a protein concentrated soft dairy cream that acquires also fat mimicking functionality. Aiming at monitoring the effects of this recycling process on the products’ metabolic profiles, samples (n = 8) of WHEY, MPW and two sub-types of FMPW were analysed by combining direct analysis in real time coupled with high resolution mass spectrometry (DART-HRMS). The most informative ions were used to build a partial least squared discriminant analysis (PLS-DA) model to assess the biochemical compounds that characterize and differentiate WHEY from MPW and FMPW. The DART-HRMS fingerprints acquired in negative mode accurately differentiated samples throughout the steps of microparticulation and fermentation. Post-fermentation, greater relative abundances of lactic acid, glucosamine and histidyl-aspartic acid were detected in both subtypes of FMPW, which were moderately differentiated by DART-HRMS. Moreover, while WHEY and MPW contained high relative abundances of hydroxyglutaric and malic acids, the fermented derivates (FMPW) were characterised by elevated levels of volatile compounds (tetradecanal, hexadecene and tetradecene) and fermentative end-products (diethyltartrate and histidyl-aspartic acid). DART-HRMS successfully captured a pool of informative biomarkers useful to understand the chemical and metabolomic changes occurring in microparticulation and fermentation processes used to recycle whey. This analytical technique is an operative supporting step needed for comprehensive assessment of the nutritional and organoleptic properties of the proposed whey-based soft cream dairy food.

IntroductionCongenital deafness is a pathological entity that represents an economical and social burden, affecting up to 0.2% of newborns in Europe. Sensorineural hearing loss (SHL) is caused by a variety of factors, including congenital abnormalities, perinatal infectious diseases and genetic syndromes. The inner ear’s vestibular system, nestled alongside the auditory organs, is crucial for balance maintenance. Its close connection with the auditory system means that disturbances in one often coincide with disturbances in the other, highlighting their intertwined functions. With this review we aim to describe objective vestibular tests found in literature and to study their use for diagnosis of vestibular disturbances in patients affected by congenital deafness.MethodsThe review is conducted with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. The search string used was: [(congenital deafness) OR (congenital hearing loss) OR (congenital hypoacusia)] AND [(vestibular disorders) OR (vertigo)]. An initial abstract reading selection was made, and a subsequent comprehensive full-text reading. For each article, we identified the type of vestibular test utilized and its corresponding outcome.ResultsOut of the initial—papers identified through the search string—articles met the eligibility criteria for further analysis through abstract and full-text reading. After further selection—articles were chosen for detailed examination, focusing on the data of patients.ConclusionCongenital hearing loss profoundly affects a child’s development, especially in language and communication skills, and it is frequently associated with a pathological vestibular system. Early identification allows timely intervention with personalized therapies. In current literature, there is still no gold standard test to identify balance disorders in patients with congenital hearing loss. There is considerable variability on the subject due to the inclusion of diverse patients with various diagnoses, alongside a wide range of available technologies. Managing such conditions necessitates collaboration among healthcare providers, ensuring comprehensive care through prompt diagnosis and personalized treatment plans. Ongoing research aims to further improve screening methods and develop precision medicine approaches tailored to individual needs.

Climate reconstructions of the last millennium rely on networks of high-resolution and well-dated proxy records. This study presents age-at-depth data and preliminary results from the new Mount Brown South (MBS) ice cores, collected at an elevation of 2084 m on the boundary of Princess Elizabeth Land and Kaiser Wilhelm II Land in East Antarctica. We show an initial analysis of the site meteorology, mean annual chemical species concentrations and seasonal cycles, including the identification of a seasonal cycle in fluoride concentrations. The annually resolved chronologies were developed from the chemistry data using a site-specific layer-counting methodology that employed seasonally varying trace chemical species and stable water isotopic ratios, combined with alignment to known volcanic horizons. The uncertainty in the determination of annual horizons via layer counting was also quantified. The chronologies developed include the “Main” 295 m record spanning 1137 years (873–2009 CE) and three surface cores spanning the most recent 39–52 years up to the surface age at the time of drilling (austral summer 2017/2018). Mean annual trace chemical concentrations are compared to the Law Dome ice core (located 1130 km east of the Mount Brown South site) and discussed in terms of atmospheric transport. The MBS chronologies presented here – named MBS2023 – will underpin the development of new palaeoclimate records spanning the past millennium from this under-represented region of East Antarctica.

Background/Aim: Prevalence of gastroduodenal endoscopic and histological lesions may modify over time due to different factors. We assessed both macroscopic and histological lesions currently detected at upper endoscopy performed in routine practice. Patients and Methods: Clinical, endoscopic, and histological data of consecutive adult patients referred for upper endoscopy in the 28 participating centres were analysed. Only patients who underwent the first endoscopic examination were considered. Prevalence of erosive/ulcerative lesions, cancers and extensive precancerous lesions in the stomach, and Helicobacter pylori infection was computed. Results: A total of 1,431 patients underwent endoscopy for gastro-oesophageal reflux symptoms (31.5%), dyspepsia (29.4%), or alarm symptoms (18.5%). Erosive oesophagitis or Barrett’s oesophagus was detected in 210 (14.7%) cases, peptic ulcer in 49 (3.4%), and a neoplastic lesion in 17 (1.2%). H. pylori was present in 201 (22.6%) cases, and extensive precancerous lesions on gastric mucosa in 46 (5.6%) patients. Gastric lesions were more prevalent in patients aged ≥50 years (26% vs. 18%; p = 0.001), and peptic ulcers were more frequently detected in patients with H. pylori (9.4% vs. 2.3%; p = 0.001) and in males (5.8% vs. 1.6%; p = 0.001), while neoplastic lesions in patients with alarm symptoms (3.8% vs. 0.6%; p = 0.001). Conclusions: The overall endoscopic lesions were more prevalent in patients aged ≥50 years, peptic ulcer and erosions were more frequent in H. pylori-infected patients, and extensive gastric precancerous lesions were present in less than 6% of cases.

Background/Objectives: New SARS-CoV-2 variants are continuously emerging, making it essential to assess the efficacy of vaccine-induced immune protection. Limited information is available regarding T cell responses to BA.2.86 and JN.1 variants, particularly in elderly individuals. Methods: We evaluated T cell and total IgG responses against the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 strain, as well as BA.2.86 and JN.1 omicron subvariants, in two groups of subjects. One group consisted of SARS-CoV-2-exposed elderly individuals who were fully vaccinated with the BNT162B2 mRNA vaccine, with a booster dose of the updated 2023–2024 COVID-19 vaccine (XBB.1.5) at least 15 days after receiving a booster dose of the updated 2023–2024 COVID-19 vaccine. The second group consisted of healthcare workers who were unexposed to SARS-CoV-2 one month after the booster dose of the first-generation BNT162b2 mRNA vaccine. T cell activation-induced markers (AIM) and IFN-γ secretion were evaluated by flow cytometry and ELISpot assays, respectively. Results: Elderly subjects showed reduced IgG levels against JN.1 compared with the ancestral strain. BA.2.86 stimulation resulted in lower IFN-γ levels in the elderly versus the COVID-19-naïve group. AIM analysis showed that among T cells, CD4+ were the most responsive, with a reduced proportion of JN.1-reactive CD4+ T cells compared with the ancestral strain in the SARS-CoV-2-unexposed group. Despite receiving the updated booster, the elderly group showed reduced CD4+ T cell reactivity to BA.2.86. Conclusions: The XBB.1.5-containing vaccine induced lower CD4+ T cell responses against BA.2.86 in the elderly. CD4+ T cells from BNT16b2-vaccinated, COVID-19-naïve subjects recognized ancestral and BA.2.86 RBD strains while showing reduced responses to JN.1. These results emphasize the need for tailored vaccine strategies for emerging variants, particularly in vulnerable populations.

BackgroundKnown risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort.MethodsSingle nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer-related cell types.ResultsWe identified statistically significant risk associations with CNVs at known EOC risk genes; BRCA1 (PEOC = 1.60E-21; OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4; odds ratio [OR]HGSOC = 5.74 del), and BRCA2 (PHGSOC = 7.0E-4; ORHGSOC = 3.31 deletion). Four suggestive associations (P

Since the 1980s, Geographical Information Systems (GIS) have been integrated into animal farming technologies for purposes such as enhancing production performances and veterinary epidemiology. In aquaculture, however, there seems to be limited application of GIS, and its potential is widely overlooked, especially for aquatic animal health management. This study describes the results of a world expert opinion elicitation on the current implementation of GIS for surveillance and disease response in the aquatic animal health domain. An online survey was submitted in autumn 2023, including both closed and open questions. With a response rate of 41.2% (21 out of 51), the answer analysis highlighted that, especially when knowledge and practical skills in geomatics, information technology and remote sensing are required, a group of advanced GIS technologies is underutilized (web-based solutions, SDI, citizen science). An artificial intelligence-based inductive text analysis was performed confirming a limited exploitation of GIS mainly due to management (financial support, training, collaboration) and methodology (data suitability, modelling analyses and integration) constraints. Furthermore, despite acknowledging the importance of planning in GIS project development, most experts did not follow any written or unwritten procedures that, according to their answers, should in fact encompass sustainable principles (integration of GIS solutions into other applications or processes), and reuse of resources (guidelines and best practices, data, methods, layouts). Shared guidelines for developing GIS projects, identifying available data sources, and long-term-maintenance planning of GIS and related geospatial data, should be pursued for using GIS technologies more effectively in the aquatic animal health domain.

Lameness is a widespread multifactorial condition affecting the health and performance of dairy cows. Despite the growing support by precision farming technologies, farmers still lack reliable data-driven tools to early identify lame cows. This study used a synthesis of reviews to identify cow’s behavioural and productive parameters most related to lameness and estimate their deviation due to a lameness event. The methodological approach used reviews as starting point to identify the most pertinent studies with the intention of extracting and analysing data from these primary studies. The final dataset used information collected from 31 research papers, cited in 15 reviews, and involved more than 25,000 dairy cows. Five parameters were suitable for the meta-analysis: one about eating behaviour (eating time), three regarding activity and resting behaviour (lying bouts, lying bout duration and lying time) and milk yield. The meta-analysis revealed that all parameters had a significant deviation in cows affected by lameness. The calculation of the pooled means allowed to quantify a mean value for the deviation imposed by a severe lameness event from the value recorded on nonlame cows. Compared to a nonlame animal, a lame cow had a significant negative deviation for eating time (−39 min/day), number of lying bouts (−0.5/day), and milk yield (−3 kg/day). Lame cows had positive deviations for lying bout duration (+12 min/bout) and daily lying time (+42 min/day). The individual or combined use of these mean deviation values as alarm reference thresholds could improve the accuracy of the current automated lameness detection systems.

Here we present the high-resolution continuous flow analysis (CFA) data from the top 479 m of the East Greenland Ice coring Project (EGRIP) ice core covering the past 3.8 kyr. The data consist of 1 mm depth-resolution profiles of calcium, sodium, ammonium, nitrate, and electrolytic conductivity as well as decadal averages of these profiles. The nominally 1 mm data represent an oversampling of the record as the true resolution is limited by the analytical setup to approximately 1 cm. Alongside the data we provide a description of the measurement setup, procedures, the relevant references for the specific methods as well as an assessment of the precision of the measurements, the sample-to-depth assignment, and the depth and temporal resolution of the data set. The error in absolute depth assignment of the data may be on the order of 2 cm; however, relative depth offsets between the records of the individual species are only on the order of 1 mm. The presented data have sub-annual resolution over the entire depth range and have already formed part of the data for an annually layer-counted timescale for the EGRIP ice core used to improve and revise the multi-core Greenland ice-core chronology (GICC05) to a new version, GICC21 (Sinnl et al., 2022). The data are available in full 1 mm resolution and decadal averages on PANGAEA (https://doi.org/10.1594/PANGAEA.945293, Erhardt et al., 2022b).

Abstract Cell annotation is a crucial methodological component to interpreting single cell and spatial omics data. These approaches were developed for single cell analysis but are often biased, manually curated and yet unproven in spatial omics. Here we apply a stemness model for assessing oncogenic states to single cell and spatial omic cancer datasets. This one-class logistic regression machine learning algorithm is used to extract transcriptomic features from non-transformed stem cells to identify dedifferentiated cell states in tumors. We found this method identifies single cell states in metastatic tumor cell populations without the requirement of cell annotation. This machine learning model identified stem-like cell populations not identified in single cell or spatial transcriptomic analysis using existing methods. For the first time, we demonstrate the application of a ML tool across five emerging spatial transcriptomic and proteomic technologies to identify oncogenic stem-like cell types in the tumor microenvironment.

ABSTRACT Objective To determine whether low muscle strength and low gait speed increase the risk of disability related to basic activities of daily living in community-dwelling older adults. Methods A longitudinal study (9 years of follow-up) was conducted with 390 older adults who were independent in basic activities of daily living at baseline and answered the Katz Index at follow-up. Associations were determined using Pearson’s χ2 test with a 5% significance level and logistic regression analysis. Results Increases in prevalence between baseline and follow-up were observed for low muscle strength (17.5%-38.2%), slow gait speed (26.0%-81.1%), and functional dependence (10.8%-26.6%). At follow-up, 11.7% of the participants had concomitant functional dependence, slow gait speed, and low muscle strength. Slow gait speed remained a predictor of dependence in basic activities of daily living (odds ratio=1.90; 95% confidence interval=1.06-3.41). Conclusion Slow gait speed is a predictor of functional dependence, constituting an important variable for screening functional decline.

BackgroundPrecision in evaluating underweight and overweight status among children and adolescents is paramount for averting health and developmental issues. Existing standards for these assessments have faced scrutiny regarding their validity. This study investigates the age and height dependencies within the international standards set by the International Obesity Task Force (IOTF), relying on body mass index (BMI), and contrasts them with Japanese standards utilizing the percentage of overweight (POW).MethodWe scrutinized a comprehensive database comprising 7,863,520 children aged 5–17 years, sourced from the School Health Statistics Research initiative conducted by Japan's Ministry of Education, Culture, Sports, Science, and Technology. Employing the quantile regression method, we dissected the structure of weight-for-height distributions across different ages and sexes, quantifying the potentially biased assessments of underweight and overweight status by conventional criteria.ResultsApplying IOFT criteria for underweight assessment revealed pronounced height dependence in males aged 11–13 and females aged 10–11. Notably, a discernible bias emerged, wherein children in the lower 25th percentile were classified as underweight five times more frequently than those in the upper 25th percentile. Similarly, the overweight assessment displayed robust height dependence in males aged 8–11 and females aged 7–10, with children in the lower 25th percentile for height deemed obese four or five times more frequently than their counterparts in the upper 25th percentile. Furthermore, using the Japanese POW criteria for assessment revealed significant age dependence in addition to considerably underestimating the percentage of underweight and overweight cases under the age of seven. However, the height dependence for the POW criterion was smaller than the BMI criterion, and the difference between height classes was less than 3-fold.ConclusionOur findings underscore the intricacies of age-dependent changes in body composition during the growth process in children, emphasizing the absence of gold standards for assessing underweight and overweight. Careful judgment is crucial in cases of short or tall stature at the same age, surpassing sole reliance on conventional criteria results.

Critical developmental “master transcription factors” (MTFs) can be subverted during tumorigenesis to control oncogenic transcriptional programs. Current approaches to identifying MTFs rely on ChIP-seq data, which is unavailable for many cancers. We developed the CaCTS (Cancer Core Transcription factor Specificity) algorithm to prioritize candidate MTFs using pan-cancer RNA sequencing data. CaCTS identified candidate MTFs across 34 tumor types and 140 subtypes including predictions for cancer types/subtypes for which MTFs are unknown, including e.g. PAX8, SOX17, and MECOM as candidates in ovarian cancer (OvCa). In OvCa cells, consistent with known MTF properties, these factors are required for viability, lie proximal to superenhancers, co-occupy regulatory elements globally, co-bind loci encoding OvCa biomarkers, and are sensitive to pharmacologic inhibition of transcription. Our predictions of MTFs, especially for tumor types with limited understanding of transcriptional drivers, pave the way to therapeutic targeting of MTFs in a broad spectrum of cancers.

RESUMO No contexto da Rio+20 e na perspectiva da garantia da saúde de todos, este ensaio discutiu um novo tipo de pensar e de realizar a participação dos povos, tradicionalmente explorados e excluídos por efeito dos modelos de desenvolvimento capitalistas e colonizadores da vida humana e da natureza. Para tanto, o ‘desenvolvimento brasileir o’foi analisado com foco no agronegócio e suas contradições, e criticado mediante a concepção do Bem Viver. Foi proposto aqui vincular a ideia do Bem Viver às demandas dos povos que lutam por outro mundo possível e que poderão ser concretizadas mediante dimensões contra-hegemônicas de poder, de saber e de direitos, no âmbito de um projeto emancipatório.