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Aims: Patients with PTEN hamartoma tumour syndrome (PHTS) have an increased risk of developing cancer due to a pathogenic germline variant in the PTEN tumour suppressor gene. Early recognition of PHTS facilitates initiation of cancer surveillance which is highly effective in preventing the development of advanced malignancies. PHTS is rare and due to its varied phenotype, even within families, oral abnormalities may be a valuable tool in the identification of these patients at an early stage before cancer development. Materials and methods: Between 1997 and 2020, phenotypic characteristics were evaluated in 81 paediatric (median age: 9 years) and 86 adult (median age: 40 years) PHTS patients by one of 2 medical experts during yearly surveillance visits at a Dutch PHTS expertise centre. Oral features evaluated included gingival hypertrophy, oral papillomas, and high palate (in adults). Results: Within adults, gingival hypertrophy was present in 94%, oral papillomas in 88%, and a high palate in 89%. All adult patients had at least one of these oral features, and 99% showed at least 2 oral features. Oral features were less common in paediatric patients, especially under 11 years of age. Gingival hypertrophy was observed in 44% and oral papillomas in 54% of paediatric patients. Conclusions: The presence of 2 or 3 oral features may indicate PHTS in adults or adolescents, especially if macrocephaly is present. Dental professionals are well-positioned to recognise these oral manifestations could be related to PHTS. They can initiate an overall clinical assessment of the patient by alerting the patient's medical practitioner of the findings and the possible need for genetic testing. This could significantly improve outcomes, including life expectancy, for patients and possibly for their relatives. Clinical relevance: Dental professionals are ideally placed to recognise oral features and initiate early assessment of PHTS which could significantly improve patient outcomes.

Background: Asthma is characterized by phenotypes of different clinical, demographic, and pathological characteristics. Identifying the profile of exhaled volatile organic compounds (VOCs) in asthma phenotypes may facilitate establishing biomarkers and understanding asthma background pathogenesis. This study aimed to identify exhaled VOCs that characterize severe asthma phenotypes among patients with asthma. Methods: This was a multicenter cross-sectional study of patients with severe asthma in Japan. Clinical data were obtained from medical records, and questionnaires were collected. Exhaled breath was sampled and subjected to thermal desorption gas chromatography-mass spectrometry (GC/MS). Results: Using the decision tree established in the previous nationwide asthma cohort study, 245 patients with asthma were divided into five phenotypes and subjected to exhaled VOC analysis with 50 healthy controls (HCs). GC/MS detected 243 VOCs in exhaled breath samples, and 142 frequently detected VOCs (50% of all samples) were used for statistical analyses. Cluster analysis assigning the groups with similar VOC profile patterns showed the highest similarities between phenotypes 3 and 4 (early-onset asthma phenotypes), followed by the similarities between phenotypes 1 and 2 (late-onset asthma phenotypes). Comparisons between phenotypes 1–5 and HC revealed 19 VOCs, in which only methanesulfonic anhydride showed p

Background: The carrying rate of thalassemia is high in Quanzhou city. However, there are few large-scale studies on the correlation analysis between genotype and phenotype of thalassemia in Quanzhou. In this study, the genotype and phenotype data of 1076 individuals with thalassemia in Quanzhou city were analyzed to provide reference data for screening and diagnosis of thalassemia in this region. Material and methods: Reverse dot blot hybridization (RDB-PCR), Gap-PCR and nested PCR were used to detect the thalassemia genotype. Clinical and hematological parameters of 1076 individuals of thalassemia were collected to analyze the correlation between genotype and phenotype. Results: Among 2997 subjects, 1076 cases diagnosed as thalassemia gene carrier or patients, with detection rate 35.9 %, among which Southeast Asian deletion (--SEA)/αα was the most common α-thalassemia genotype (48.4 %) and one rare genotype was detected: HKαα/--SEA (0.1 %). Subjects with thalassemia alone showed the least severe symptoms of anemia with higher red blood cell count (RBC) and hemoglobin (Hb), lower red blood cell distribution width (RDW) than those with iron deficiency (ID) or iron overload (IO) (p

Purpose: To explore the characteristics of the clinical phenotype of ARDS based on Machine Learning. Methods: This is a study on Machine Learning. Screened cases of acute respiratory distress syndrome (ARDS) in the eICU database collected basic information in the cases and clinical data on the Day 1, Day 3, and Day 7 after the diagnosis of ARDS, respectively. Using the Calinski-Harabasz criterion, Gap Statistic, and Silhouette Coefficient, we determine the optimal clustering number k value. By the K-means cluster analysis to derive clinical phenotype, we analyzed the data collected within the first 24 h. We compared it with the survival of cases under the Berlin standard classification, and also examined the phenotypic conversion within the first 24 h, on day 3, and on day 7 after the diagnosis of ARDS. Results: We collected 5054 cases and derived three clinical phenotypes using K-means cluster analysis. Phenotype-I is characterized by fewer abnormal laboratory indicators, higher oxygen partial pressure, oxygenation index, APACHE IV score, systolic and diastolic blood pressure, and lower respiratory rate and heart rate. Phenotype-II is characterized by elevated white blood cell count, blood glucose, creatinine, temperature, heart rate, and respiratory rate. Phenotype-III is characterized by elevated age, partial pressure of carbon dioxide, bicarbonate, GCS score, albumin. The differences in ICU length of stay and in-hospital mortality were significantly different between the three phenotypes (P

Motor subtypes in Parkinson's Disease (PD) are unstable over time, limiting mechanistic insights and biomarker discovery. We focused on Rest Tremor (RT) as a symptom to test for phenotype stability and link it to specific circuits and disease mechanisms. Using the PPMI cohort data over 5 years we found that RT is more stable than classical Tremor-Dominant definitions, a stability also seen for RT response to therapy. At time of diagnosis, the population of therapy-resistant RT patients was enriched with a brain-first PD profile as predicted by a-Synuclein origin site and connectome (SOC) model. Resistant-RT patients have lower gastrointestinal and cardiovascular symptoms, lower prevalence of probable REM-Sleep behaviour disorder, and higher dopaminergic asymmetry compared to therapy-responsive or no tremor patients. Treating RT as a distinct phenomenon revealed a relative phenotypic stability with treatment response being linked to different patterns of disease progression.

Increased uses rather an extensive misuse of antibiotics due to easy availability and easy access have resulted in antibiotic resistance as a global crisis. The speed of discovery of new antibiotics has slowed down recently. Therefore, there is a need to reduce the rate of increase in resistance against the presently available antibiotics, or else many infections may be left untreatable or difficult to be treated due to the high prevalence of resistance. The judicious use of broad-spectrum antibiotics can control the increase in resistance profile. Various techniques are presently being used for the detection of antibiotic resistance. Conventional phenotypic methods are preferred that are highly reliable but are much more time-consuming. The patients cannot spare more time as the infection keeps increasing. The results with genotypic methods are obtained within 24 h as compared to phenotypic methods. Hence, recent molecular methods like qPCR can be used for detection. In this review, we present an overview of various methods useful for the detection of antibiotic resistance, with emphasis on their advantages and limitations. The review also emphasizes qPCR to be the most preferred method out of all because of various advantageous factors.

A study was conducted in 2022 in the Liban Jawi district to characterize the breeding practices of indigenous chickens. A total of 192 farmers were surveyed, revealing diverse breeding objectives, including income generation, egg consumption, savings, and meat consumption. Limited selective breeding was observed, with plumage color, egg number, broodiness, hatchability, and male body weight as common selection traits. Most farmers practiced uncontrolled natural mating and were unaware of the risks of inbreeding. Culling underproductive chickens, undesirable colored cockerels, or pullets at an early age, along with selling or slaughtering, were employed to prevent unwanted mating. Correspondence Analysis (CA) revealed significant relationships among phenotypic traits, with Dimension 1 accounting for 39.43 % of total inertia, indicating that environmental conditions heavily influence trait selection. The Chi-Squared Distance analysis highlighted strong preferences for Egg Number (D = 15.23) and Hatchability (D = 12.45), both showing highly significant P-values (p = 0.001 and p = 0.002 respectively). Additionally, farmers expressed significant preferences for Disease Resistance (D = 11.56, p = 0.003) and Body Size (D = 10.12, p = 0.012). This research provides valuable insights into the breeding practices of indigenous chickens in the unique context of the Liban Jawi District, Ethiopia. By combining qualitative and quantitative analyses, the study emphasizes the significance of indigenous knowledge, identifies challenges, and underscores the implications for sustainable rural livelihoods. The findings advocate for effective trait selection and the implementation of controlled mating systems to mitigate inbreeding risks and enhance productivity in indigenous chicken populations.

Background: KIDINS220 encodes a transmembrane scaffold protein, kinase D-interacting substrate of 220 kDa, that regulates neurotrophin signaling. Variants in KIDINS220 have been linked to spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO) syndrome or prenatal fatal cerebral ventriculomegaly and arthrogryposis (VENARG). This study aimed to investigate the genotype-phenotype correlation of pathogenic KIDINS220 variants. Methods: We performed whole-exome sequencing on a patient with SINO syndrome and epilepsy. Identified pathogenic variants were confirmed using Sanger sequencing and evaluated with in silico tools. A comprehensive literature review was conducted to analyze the genetic and phenotypic data of both the newly diagnosed patient and previously reported cases with KIDINS220 variants. Results: We identified novel compound heterozygous variants in KIDINS220, c.1556C > T (p.Thr519Met) and c.2374C > T (p.Arg792*), in the patient. Our analysis revealed that biallelic loss-of-function variants in KIDINS220 are associated with VENARG or autosomal recessive SINO (AR-SINO), whereas carboxy-terminal truncated variants that escape nonsense-mediated mRNA decay and lack amino acid residues 1507–1529 are linked to autosomal dominant SINO (AD-SINO). Patients with AR-SINO exhibit more severe clinical features compared to those with AD-SINO. Conclusions: Our study expands the spectrum of KIDINS220 variants associated with AR-SINO and provides a valuable genotype-phenotype correlation for pathogenic KIDINS220 variants.

Background: Cardiac sarcoidosis (CS) is a rare but potentially fatal inflammatory cardiomyopathy. Objectives: The authors studied temporal changes in the incidence, characteristics, and outcome of CS. Methods: A retrospective analysis was made of a 30-year nationwide cohort of CS. Results: The cohort comprised 511 patients with a median age of 52 years and female preponderance (69%). Altogether 77, 166, and 268 cases of CS were diagnosed in years 1988 to 2009, 2010 to 2014, and 2015 to 2019, respectively; the 5-year count of 2015 to 2019 was 134-fold the count of 1990 to 1994 (268/2) and 18-fold the count of 2000 to 2004 (268/15). Prior to 2010, compared with the later periods, CS presented more often with ventricular tachycardia/fibrillation (prevalence 36% vs 19% in 2010-2014 and 11% in 2015-2019, P

Objectives: To investigate the prevalence of Mycobacterium abscessus complex (MABC), drug resistance characteristics, and the relationship between clarithromycin (CLA) susceptibility and MABC genotype in Chongqing, China. Methods: A total of 434 NTM patient isolates were collected between October 2018 and October 2019. Isolates confirmed to be non-tuberculous mycobacteria (NTM) were tested for minimal inhibitory concentrations of antimicrobial agents. In addition, rrl and erm(41) gene sequences were used to analyze the acquired macrolide resistance and inducible macrolide resistance. Results: Overall, 17 different NTM species were detected, of which M. abscessus (22.6 %, 91/403) was most prevalent. Amikacin, CLA, azithromycin and cefoxitin exhibited potent activities against MABC organisms, but no significant differences were observed in drug resistance rates between M. abscessus and M. massiliense (P > 0.05). On day 3 of culture, the acquired resistance rate against CLA was 7.4 % (9/121). Of 41 MABC isolates with inducible CLA resistant, 95.1 % (39/41) isolates belonged to the erm(41) T28 sequevar, while the remaining 4.9 % (2/41) possessed the M. massiliense genotype. All erm(41) C28 sequevar isolates were sensitive to CLA on day3 and day 14 of culture. Meanwhile, of the 5 erm(41) T28 isolates with acquired resistance, all possessed rrl 2058/2059 mutations, including 3 isolates with A2058C mutation and 2 isolates with A2059G mutation. While 2 of the 4 M. massiliense isolates with acquired resistance possessed the A2059G mutation, and one isolate possessed the A2058G mutation. Conclusion: Erm(41) and rrl gene could serve as useful markers for predicting macrolide susceptibility of MABC complex isolates.

Maca (Lepidium meyenii), mainly grown in Peru, is a traditional herbal medicine that is mostly used to improve sperm motility and serum hormone levels. Maca phenotypes are represented by purple, black, yellow, white, and mixed colors. Recently, a method for Maca cultivation has been established in Japan. Therefore, we determined the effects of different phenotypes and portions on the antioxidant activities and total polyphenols, anthocyanins, and benzyl-glucosinolate contents in Japanese Maca. Purple Maca skin possessed the highest contents of both total polyphenols, antioxidant activity and anthocyanin content in all Macas. Regarding the benzyl-glucosinolate content, white maca had the highest content and was not correlated with antioxidant activity. In the present study, we revealed that purple Maca skin is recommended for high polyphenol content, antioxidant activity, and anthocyanin content. The results of this study will be useful for selecting phenotypes for the improvement of antioxidant activity or hormone balance.

The dynamics of cattle body chemical composition during growth and fattening periods determine animal performance and beef carcass quality. The aim of this study was to estimate the empty body (EB) and carcass chemical composition of growing beef-on-dairy crossbred bulls (Brown Swiss breed as dam with Angus, Limousin or Simmental as sire) using three-dimensional (3D) imaging. The 3D images of the cattle’s external body shape were recorded in vivo on 48 bulls along growth trajectory (75–520 kg BW and 34–306 kg hot carcass weight [HCW]; set 1) and on 70 bulls at target market slaughter weight, including 18 animals from set 1 (average 517 ± 10 kg BW and 289 ± 10 kg HCW; set 2). The linear, circumference, curve, surface and volume measurements on the 3D body shape were determined. Those predictive variables were used in partial least square regressions, together with the effect of the sire breed whenever significant (P

ABSTRACT: Eggshell and shank color in poultry is an intriguing topic of research due to the roles in selection, breed recognition, and environmental adaptation. This study delves into the genomics foundations of shank and eggshell pigmentation in Italian local chickens through genome-wide association studies analysis to uncover the mechanisms governing these phenotypes. To this purpose, 483 animals from 20 local breeds (n = 466) and 2 commercial lines (n = 17) were considered and evaluated for shank and eggshell color. All animals were genotyped using the Affymetrix Axiom 600 K Chicken Genotyping Array. As regards shank color, the most interesting locus was detected on chromosome Z, close to the TYRP1 gene, known to play a key role in avian pigmentation. Additionally, several novel loci and genes associated with shank pigmentation, skin pigmentation, UV protection, and melanocyte regulation were identified (e.g., MTAP, CDKN2A, CDKN2B). In eggshell, fewer significant loci were identified, including SLC7A11 and MITF on chromosomes 4 and 12, respectively, associated with melanocyte processes and pigment synthesis. This comprehensive study shed light on the genetic architecture underlying shank and eggshell color in Italian native chicken breeds, contributing to a better understanding of this phenomenon which plays a role in breed identification and conservation, and has ecological and economic implications.

Hereditary angioedema (HAE) encompasses a group of diseases characterized by recurrent, genetically mediated angioedema associated with increased vascular permeability primarily due to bradykinin. The disease poses diagnostic challenges, leading to underdiagnosis and delayed therapy. Severe manifestations include laryngeal and intestinal angioedema, contributing to significant morbidity and mortality. If left undiagnosed, the estimated mortality rate of the disease ranges from 25% to 40% due to asphyxiation caused by laryngeal angioedema. There is a pressing need to enhance awareness of hereditary angioedema and its warning signs. The acronym “H4AE” may facilitate the memorization of these signs. This study comprehensively reviews clinical, laboratory, and physiopathological features of documented HAE subtypes. The study advocates for an improved HAE classification based on endotypes, building on the knowledge of angioedema pathophysiology. The proposed endotype classification of HAE offers a clear and applicable framework, encouraging advancements in disease understanding and classification.

Background: The innate mechanisms associated with viral exacerbations in preschool children with recurrent wheezing are not understood. Objective: We sought to assess differential gene expression in blood neutrophils from preschool children with recurrent wheezing, stratified by aeroallergen sensitization, at baseline and after exposure to polyinosinic:polycytidylic acid (poly(I:C)) and also to examine whether poly(I:C)-stimulated blood neutrophils influenced airway epithelial gene expression. Methods: Blood neutrophils were purified and cultured overnight with poly(I:C) and underwent next-generation sequencing with Reactome pathway analysis. Primary human small airway epithelial cells were treated with poly(I:C)-treated neutrophil culture supernatants and were analyzed for type 1 interferon gene expression with a targeted array. Symptoms and exacerbations were assessed in participants over 12 months. Results: A total of 436 genes were differently expressed in neutrophils from children with versus without aeroallergen sensitization at baseline, with significant downregulation of type 1 interferons. These type 1 interferons were significantly upregulated in sensitized children after poly(I:C) stimulation. Confirmatory experiments demonstrated similar upregulation of type 1 interferons in IL-4–treated neutrophils stimulated with poly(I:C). Poly(I:C)-treated neutrophil supernatants from children with aeroallergen sensitization also induced a type 1 interferon response in epithelial cells. Children with aeroallergen sensitization also had higher symptom scores during exacerbations, and these symptom differences persisted for 3 days after prednisolone treatment. Conclusions: Type 1 interferon responses are dysregulated in preschool children with aeroallergen sensitization, which is in turn associated with exacerbation severity. Given the importance of type 1 interferon signaling in viral resolution, additional studies of neutrophil type 1 interferon responses are needed in this population.

M1/M2 paradigm of macrophage plasticity has existed for decades. Now it becomes clear that this dichotomy doesn't adequately reflect the diversity of macrophage phenotypes in tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are a major population of innate immune cells in the TME that promotes tumor cell proliferation, angiogenesis and lymphangiogenesis, invasion and metastatic niche formation, as well as response to anti-tumor therapy. However, the fundamental restriction in therapeutic TAM targeting is the limited knowledge about the specific TAM states in distinct human cancer types. Here we summarized the results of the most recent studies that use advanced technologies (e.g. single-cell RNA sequencing and spatial transcriptomics) allowing to decipher novel functional subsets of TAMs in numerous human cancers. The transcriptomic profiles of these TAM subsets and their clinical significance were described. We emphasized the characteristics of specific TAM subpopulations – TREM2+, SPP1+, MARCO+, FOLR2+, SIGLEC1+, APOC1+, C1QC+, and others, which have been most extensively characterized in several cancers, and are associated with cancer prognosis. Spatial transcriptomics technologies defined specific spatial interactions between TAMs and other cell types, especially fibroblasts, in tumors. Spatial transcriptomics methods were also applied to identify markers of immunotherapy response, which are expressed by macrophages or in the macrophage-abundant regions. We highlighted the perspectives for novel techniques that utilize spatial and single cell resolution in investigating new ligand-receptor interactions for effective immunotherapy based on TAM-targeting.

Summary: Background: Despite more than 50 years of research and parallel improvements in hepatology and oncology, there is still today neither a treatment to prevent disease progression in primary sclerosing cholangitis (PSC), nor reliable early diagnostic tools for the associated hepatobiliary cancers. Importantly, the limited understanding of the underlying biological mechanisms in PSC and its natural history not only affects the identification of new drug targets but implies a lack of surrogate markers that hampers the design of clinical trials and the evaluation of drug efficacy. The lack of easy access to large representative well-characterised prospective resources is an important contributing factor to the current situation. Methods: We here present the SUPRIM cohort, a national multicentre prospective longitudinal study of unselected PSC patients capturing the representative diversity of PSC phenotypes. We describe the 10-year effort of inclusion and follow-up, an intermediate analysis report including original results, and the associated research resource. All included patients gave written informed consent (recruitment: November 2011–April 2016). Findings: Out of 512 included patients, 452 patients completed the five-year follow-up without endpoint outcomes. Liver transplantation was performed in 54 patients (10%) and hepatobiliary malignancy was diagnosed in 15 patients (3%). We draw a comprehensive landscape of the multidimensional clinical and biological heterogeneity of PSC illustrating the diversity of PSC phenotypes. Performances of available predictive scores are compared and perspectives on the continuation of the SUPRIM cohort are provided. Interpretation: We envision the SUPRIM cohort as an open-access collaborative resource to accelerate the generation of new knowledge and independent validations of promising ones with the aim to uncover reliable diagnostics, prognostic tools, surrogate markers, and new treatment targets by 2040. Funding: This work was supported by the Swedish Cancer Society, Stockholm County Council, and the Cancer Research Funds of Radiumhemmet.

Germplasm resource innovation is a crucial factor for cultivar development, particularly within the context of hybrid rice breeding based on the three-line system. Quan 9311A, a cytoplasmic male sterile (CMS) line, has been successfully cultivated using rice restoration materials and extensively employed as a female parent in hybrid breeding program in China. This line was developed by crossing the CMS line Zhong 9A with a two-line restorer line 93-11, with the intention of eliminating the restoring ability of 93-11 while retaining the sterility gene WA352c from Zhong 9A. Quan 9311A effectively amalgamates the most favorable agronomic traits from both parental lines. In this study, the relationship between phenotypic characteristics and the known functional genes of Quan 9311A were analyzed using the rice genome navigation technology based on whole-genome sequencing. The findings revealed that Quan 9311A harbors multiple superior alleles from both 93-11 and Zhong 9A, providing exceptional agronomic traits that are unavailable in earlier CMS lines. Despite the removal of the fertility restorer gene Rf3 from 93-11, numerous chromosomal segments from 93-11 persist in the Quan 9311A genome. Furthermore, the hybrid rice Quanyousimiao (QYSM) and the restorer line Wushansimiao (WSSM) were used as examples to illustrate the important role of Quan 9311A as the female parent in heterosis. It was found that QYSM carries a great number of superior alleles, which accounts for its high grain yield and wide adaptability. These insights not only advanced the utilization of hybrid rice pairing groups but also provided guidance for future breeding endeavors. The study introduced innovative concepts to further integrate genomics with traditional breeding techniques. Ultimately, Quan 9311A signified a significant milestone in rice breeding technology, opening up novel avenues for hybrid rice development.

ABSTRACT: This experiment was designed to investigate the relation of high and low methane-yield phenotypes with body weight (BW), dry matter intake (DMI), lactation performance, enteric CH4 emissions, and rumen fermentation parameters in lactating dairy cows. A total of 130 multi- and primiparous Holstein cows were screened for enteric CH4 emissions using the GreenFeed system (C-Lock Inc.). Out of these 130 cows, 5 were identified as phenotypically high (HM) and 5 as phenotypically low (LM) CH4 emitters. Cows in the LM group had lower daily enteric CH4 emissions than cows in the HM group (on average 346 vs. 439 g/d, respectively), lower CH4 yield (15.5 vs. 20.4 g of CH4/kg of DMI), and CH4 intensity (13.2 vs. 17.0 g of CH4/ kg of energy-corrected milk yield). Enteric emissions of CO2 and H2 did not differ between HM and LM cows. These 10 cows were blocked by parity, days in milk, and milk production, and were used in a 5-wk randomized complete block design experiment. Milk composition, production, and BW were also not different between LM and HM cows. The concentration of total volatile fatty acids in ruminal contents did not differ between CH4 phenotypes, but LM cows had a lower molar proportion of acetate (57 vs. 62.1%), a higher proportion of propionate (27.5 vs. 21.6%, respectively), and therefore a lower acetate-to-propionate ratio than HM cows. Consistently, the 16S cDNA analysis revealed the abundance of Succinivibrionaceae and unclassified Veillonellaceae to be higher in LM cows compared with HM cows, bacteria that were positively correlated with ruminal propionate concentration. Notably, Succinivibrionaceae trigger the formation of propionate via oxaloacetate pathway from phosphoenolpyruvate via Enzyme Commission: 4.1.1.49, which showed a trend to be higher in LM cows compared with HM cows. Additionally, LM cows possessed fewer transcripts of a gene encoding for methyl-CoM reductase enzyme compared with HM. In this study, low and high CH4-yield cows have similar production performance and milk composition, but total-tract apparent digestibility of organic matter and fiber fractions was lower in the former group of animals.

Microgreens are the first leafy seedlings of edible plants. Microgreen farming is yet to be automated; the main challenge for automation is the lack of a sensory mechanism to detect and quantify microgreen phenotypes. This paper presents a novel automated microgreen phenotyping method targeting yield estimation. The paper demonstrates that phenotyping can be effectively performed using a consumer-grade RGB-D camera. First, the depth and RGB images are captured. Thereafter, the plant segments are filtered and the canopy is identified. Using image processing, the canopy height and density are calculated. Both yield prediction regression analysis and a TensorFlow learning algorithm are evaluated to estimate the yield as a function of height and canopy density. The authors believe the algorithm discussed in this paper is the first phenotyping algorithm combining RGB and depth data for microgreen yield estimation.

Background: Genome association studies have shown that gene-gene interactions or epistasis play a crucial role in identifying the etiology, prognosis, and treatment response of many complex diseases beyond their main effects. Skeletal dysplasias are a heterogeneous group of congenital bone and cartilage disorders with a genetic and gen-gen interaction etiology. The current classification of skeletal dysplasias distinguishes 461 diseases in 42 groups, and the incidence of all skeletal dysplasias is more than 1 in every 5000 newborns. The objective is to present the case of a patient with four variants that generates gen-gen interactions in the skeletal dysplasia. Case presentation: A 1-year-old male patient was diagnosed with skeletal dysplasia based on prenatal ultrasound showing micromelia and pyelocalyceal dilation. Postnatal physical examination revealed body disproportion and involvement of other organs and systems. Materials and Methods: A sequencing study and deletions/duplications analysis were performed for 358 candidate genes associated with skeletal dysplasia.The GeneMANIA interface was used to evaluate the expression network of genes associated with each other for the gen-gen interaction. Results: Four pathogenic variants were obtained two heterozygous variants with pathogenic significance in SLC26A, one heterozygous pathogenic variant in CLCN7 and another heterozygous pathogenic variant in CEP120.The GeneMANIA interface reveals 77.64% physical interactions, 8.01% co-expression, 5.37% prediction, 3.63% co-localization, 2.87% genetic interactions, 1.88% route of action, and 0.60% shared protein domains. Discussion and Conclusions: These results suggest that the interaction between these genes affects the activity of the inorganic anion exchanger, leading to disorganization of collagen fibers, early mineralization, and decreased assembly of fibronectin in the bone extracellular matrix. Identifying gene-gene interactions is a fundamental step in understanding proper cell function and thus understanding the pathophysiology of many complex human diseases, improving diagnosis, and the possibilities of new personalized therapies.

Background: Noonan syndrome (NS) is relatively common but poorly recognized. We aimed to describe the phenotypic and genotypic spectrum of NS in a Chinese cohort. Method: The study retrospectively investigated consecutive pediatric patients who presented at the Guangdong cardiovascular institute between 2018 and 2020 with confirmed known NS-relevant mutations determined by exome sequencing. Dates of genetic testing, Age, sex, institution of genetic testing, mutated gene (related to NS) and its classification, heterozygosity, and parental origin were identified from the sequencing reports. Facial features, cardiac defect and other clinical characteristics were also assessed. Comparisons of categorical variables between groups were examined by Chi-square test or Fisher's exact test when appropriate. Intraclass correlation coefficient (ICC) was performed to evaluate the reliability of evaluation of facial features between different evaluators. Results: The most prevalent mutated genes were PTPN11 (37.0%) and RAF1 (19.6%), and most mutations were pathogenic (67.4%) and de novo (87.0%). Most patients were with NS-relevant facial features (97.4%) and cardiac defects (92.7%), where ventricular hypertrophy, pulmonary valve stenosis, and atrial septal defect were the most prevalent. Patients with mutated RAF1 appeared to be diagnosed at an older age than those with mutated PTPN11, and with higher prevalence of mitral regurgitation, hypertrophic cardiomyopathy, and ventricular hypertrophy, but lower prevalence of pulmonary valve stenosis and pulmonary artery stenosis. Patients presented at an age ≥2 years appeared to be with fewer NS-relevant facial features and cardiac defects than those aged

Objective: Assigning outcome labels to large observational data sets in a timely and accurate manner, particularly when outcomes are rare or not directly ascertainable, remains a significant challenge within biomedical informatics. We examined whether noisy labels generated from subject matter experts’ heuristics using heterogenous data types within a data programming paradigm could provide outcomes labels to a large, observational data set. We chose the clinical condition of opioid-induced respiratory depression for our use case because it is rare, has no administrative codes to easily identify the condition, and typically requires at least some unstructured text to ascertain its presence. Materials and methods: Using de-identified electronic health records of 52,861 post-operative encounters, we applied a data programming paradigm (implemented in the Snorkel software) for the development of a machine learning classifier for opioid-induced respiratory depression. Our approach included subject matter experts creating 14 labeling functions that served as noisy labels for developing a probabilistic Generative model. We used probabilistic labels from the Generative model as outcome labels for training a Discriminative model on the source data. We evaluated performance of the Discriminative model with a hold-out test set of 599 independently-reviewed patient records. Results: The final Discriminative classification model achieved an accuracy of 0.977, an F1 score of 0.417, a sensitivity of 1.0, and an AUC of 0.988 in the hold-out test set with a prevalence of 0.83% (5/599). Discussion: All of the confirmed Cases were identified by the classifier. For rare outcomes, this finding is encouraging because it reduces the number of manual reviews needed by excluding visits/patients with low probabilities. Conclusion: Application of a data programming paradigm with expert-informed labeling functions might have utility for phenotyping clinical phenomena that are not easily ascertainable from highly-structured data.

Objective: To explore the correlation between different CYP21A2 pathogenic gene mutations and clinical phenotypes in Congenital adrenal hyperplasia (CAH) patients. Moreover, combined with the specific phenotypes of patients in the clinic, diagnosis and treatment suggestions should be made for CAH patients. Methods: In this study, a genetic status of a Chinese family in three generations of 21-hydroxylase deficiency was comprehensively presented, and the pathogenic genes in the family were found and traced in detail. We measured CYP21A2 gene in this family by Sanger sequencing and MLPA. The trophoblast cells of female proband’s embryos were detected by PGT-M which used Copy-Number Variations of a Single Human Cell and high throughput sequencing. The CYP21A2 gene mutation site in each embryo were detected by Sanger sequencing, whole genome sequencing and single nucleotide polymorphism (SNP). Results: There are many related pathogenic genes of CAH in this family. The female proband showed a compound heterozygous mutation in the CYP21A2 gene, including a CYP21A1P/A2 fusion gene (CH-8) (classical phenotype) and a new mutation c.1034T > C (p. L354S) (unknown clinical significance). In the proband’s family, a heterozygous gene mutation of c.1034T > C and a CYP21A1P/A2 fusion gene (CH-8) was carried by her father and mother, respectively. Meanwhile, the husband of the proband also has a genetic family with related disease. Both the husband and his father carried the CYP21A2 gene c.844G > T heterozygous mutation, while his mother had no related mutation in the CYP21A2 gene. Furthermore, PGTM gene detection was carried out on the four blastocysts of the proband’s offspring through IVF. The results showed that embryos T1, T2 and T4 all carried CYP21A1P/A2 fusion gene (CH-8), as well as embryo T3 carried c.1034T > C heterozygous mutation of maternal origin. Conclusion: This case is a family report showing a complete genetic map of the proband and her family, describing the genetic process of different pathogenic genes in detail and clearly corresponding to the patient’s different phenotypes. It is speculated that the pathogenesis of CAH is caused by different mutations in the CYP21A2 gene and their interactions, which may affect the different phenotypes of CAH patients.

Background: Maturity-onset diabetes of the young, type 13 (MODY13) is a specific subclass of monogenic diabetes mellitus that does not exhibit the typical clinical manifestations of diabetes, necessitating the use of genetic testing for accurate diagnosis. With the progression of monogenic diabetes and MODY, the number of reported MODY13 cases has reached a minimum of 22. Nevertheless, there remains a dearth of information regarding patients diagnosed with MODY13 presenting synonymous variants. Case presentation: This study presents a description of the clinical and genetic features of a 9-year-old male patient diagnosed with MODY13. A noteworthy finding in this case was the occurrence of a “separation phenomenon” between C-peptide and insulin during the standard meal test. Whole exome sequencing (WES) identified a KCNJ11 c.843C > T (p.L281=) mutation in exon 1, which contradicted the previously reported phenotype. Following the onset of ketosis, the patient underwent insulin therapy for a duration of one month, during which the insulin dosage was gradually modified based on blood glucose levels. In order to maintain normoglycemia, he adhered to a diabetic dietary regimen and participated in 1–2 h of moderate exercise daily. Conclusion: The study implies that patient with KCNJ11 variant shows a “separation phenomenon” between C-peptide and insulin in standard meal test. Our report also enriched the genotype and phenotype spectrums of MODY13 and highlighted the importance of genetic testing in patients without characteristic clinical symptoms of diabetes.

Background: Neurofibroma type I (NF1) often presents with multiple clinical phenotypes due to mutations of NF1 gene. The aim of this study was to determine the phenotypic and therapeutic relevance of tumor microenvironment in NF1 patients. Methods: Tumor stem cells (TSCs) from NF1 were isolated and cultured using fluorescence activated cell sorting (FACS) and colony formation experiments. Then, flow cytometry was used to detect the surface markers, osteogenic and adipogenic differentiation were performed as well. Its tumorigenesis ability was confirmed by subcutaneous tumorigenesis in nude mice. Immunohistochemical staining was performed on neurofibroma tissues from the head and trunk with different phenotypes. The expression of BDNF in neurofibroma tissues was detected by Elisa and immunohistochemical staining. Western Blotting was used to detect the expression of p38 MAPK pathway in TSCs. The effect of BDNF neutralizing antibody on the tumorigenesis of TSCs was observed. Results: Herein, we advocate that NF1 contain a new subgroup of mesenchymal-like neurofibroma stem cells (MNSCs). Such colony-forming MNSCs preserved self-renewal, multiple differentiation and tumorigenic capabilities. More interestingly, the MNSCs isolated from neurofibroma tissues of the same patient with different phenotypes presented site-specific capabilities. Moreover, different levels of brain-derived neurotrophic factor (BDNF) in neurofibroma tissues can impact the MNSCs by activating the TrkB/p38 MAPK pathway. Systemic administration of BDNF neutralizing antibodies inhibited MNSCs’ characteristics. Conclusions: We demonstrated that BDNF can modulate MNSCs and thereby controlling different tumor phenotypes between the head and trunk regions. Application of BDNF neutralizing antibodies may inhibit p38 MAPK pathway, therefore providing a promising strategy for managing NF1.

Background: Asthma in the elderly is not as well studied as in younger age groups. Age-related immunosenescence may result in diminished TH2 inflammation, which raises a question about whether asthma in elderly patients responds well to anti-TH2 asthma biologics. Objective: We sought to determine whether asthma in elderly people has different TH2 biomarkers and clinical features compared to nonelderly people, and if disease in the 2 age groups responds differently to anti-TH2 biologics. We also aimed to identify treatment-responsive phenotypes with clinical and biomarker features that could be used to predict best response to biologics. Methods: A retrospective chart review was conducted for 56 patients (30 elderly [age ≥62 years] and 26 nonelderly [ages 18-59 years] subjects) with severe asthma treated with dupilumab or benralizumab. Differences in baseline characteristics and response to treatment were analyzed. A hierarchical cluster analysis was also performed to identify treatment-responsive phenotypes. Significance threshold was P = .05 for all analyses. Results: Baseline characteristics and TH2 biomarkers (blood eosinophil level, total IgE, aeroallergen sensitivity) were similar between elderly and nonelderly subjects. The disease in both groups responded well to biologics (improvement in ACT scores, decreased exacerbations, decreased need for prednisone), but no significant response difference was found based on age groups. Cluster analysis identified 3 phenotypes, as follows: cluster 1, youngest age, moderate eosinophil levels, lowest total IgE, few environmental allergies, and least response to biologics; cluster 2, intermediate age, lowest eosinophil level, highest IgE level, many environmental allergies, and an intermediate response to biologics; and cluster 3, oldest ages, highest eosinophil levels, high total IgE, few environmental allergies, and best response to biologics. These results confirm trends seen in another study utilizing cluster analyses showing that subjects with highest levels of IgE and eosinophils responded better to biologic treatment for asthma. Conclusion: Elderly people with asthma should be considered for biologic therapy no differently than younger people. There may be subgroups of patients with different biologic responses based on age, allergenicity, IgE, and eosinophil levels that could be used to predict treatment response.

Summary: Background: Large-scale studies are needed to clarify antimicrobial resistance in the foodborne pathogen Listeria monocytogenes (Lm) and the effectiveness of listeriosis treatment options. Here we examined the antimicrobial resistance patterns in Lm over time and assessed genotype-phenotype concordances. Methods: We analyzed 5339 Lm isolates (2908 clinical and 2431 food isolates) collected in France and overseas territories, between 2012 and 2019. Whole genome sequencing was performed for all isolates and antimicrobial resistance profiles inferred from draft assemblies. Antimicrobial susceptibility towards 22 antimicrobials was determined for all clinical isolates, and in food isolates with acquired resistance genes. Findings: All tested isolates were resistant to at least 3 different classes of antimicrobials, consistent with Lm intrinsic traits. Acquired antimicrobial resistance in Lm was rare (2.23% isolates) and more prevalent in food (mainly lineage II) compared to clinical isolates (mainly lineage I) (3.74% vs 0.98%, p 99%), except for ciprofloxacin. Acquired antimicrobial phenotypes were towards tetracyclines (mostly due to tetM), trimethoprim (dfrD), lincosamides (lnuG), macrolides (ermB, mphB) and phenicols (fexA). Interpretation: The reference treatment for listeriosis (aminopenicillins/aminoglycosides) remains effective, with no acquired resistance observed. Continuous surveillance of antimicrobial resistance in clinical and food isolates is crucial to detect the emergence of novel resistance. Funding: Institut Pasteur, INSERM, Santé Publique France, Investissement d’Avenir program Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (ANR-10-LABX-62-IBEID).

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a monogenic disorder caused by mutations in the NOTCH3 gene. The main aim of our survey was to determine if there is an association between phenotypes and genotypes across the most common NOTCH3 mutations found in CADASIL patients. We systematically searched clinical studies and genomic databases from 1996 to 2023 to first identify the most common mutations responsible for CADASIL. We found the six most common NOTCH3 missense mutations globally were the p.R75P, p.R133C, p.R141C, p.R169C, p.R182C, and p.R544C, of which p.R133C was described to occur most often. Focusing on studies with comprehensive clinical records, our analysis further suggested that the p.R75P, p.R141C, p.R182C and p.R544C genotypes were highly congruent with the presence of white matter hyperintensities on magnetic resonance imaging (MRI), which was the most common phenotypic characteristic across all four mutations. We found the p.R141C mutation was associated with increased severity of disease. We also found the average age of onset in p.R544C carriers was more than a decade later compared to the p.R141C carriers. However, statistical analysis showed there were no overall differences between the phenotypic characteristics of the two common mutations, p.R141C and p.R544C. Geographically, China and Japan were the only two countries to report all the four common mutations vis a vis p.R75P, p.R141C, p.R182C and p.R544C. There is a possibility that this is due to a combination of a founder effect, but there also could be sampling biases.

Objective: To evaluate the gingival phenotypes of healthy young adult Pakistanis attending a dental institution. Methods: A cross-sectional study of gingival phenotype, probing depth (PD), papilla height (PH), gingival width (GW), gingival thickness (GT), crown width (CW) and crown length (CL) of maxillary central incisors was conducted in 510 healthy, Pakistani young adults, aged 20–35 years, attending a regional dental hospital in Pakistan. The K-means clustering technique was employed to delineate clusters based on the characteristics of the periodontal phenotypes. The resultant data was compared with the available international findings. Results: Three quarters (76 %) of the 510 patients examined exhibited a thick gingival phenotype, and the remainder a thin phenotype. The K-means clustering deployed the individual into three different clusters 1, 2 and 3, with varying ratios of PD, GW, CW/CL, with significant variations across the three clusters (p

ABSTRACT: Tracking group-housed individual broilers using video can provide valuable information on their health, welfare, and performance, allowing breeders to identify novel or indicator traits that aid genetic improvement. However, their similar appearances make tracking individual broilers in a group-housed setting challenging. This study aimed to analyze broiler tracking on video (number of ID-switches, tracking time and distance) and examined potential tracking errors (ID-losses – location, proximity, kinematics) in an experimental pen to enable broiler locomotion phenotyping. This comprehensive analysis provided insights into the potential and challenges of tracking group-housed broilers on video with regards to phenotyping broiler locomotion. Thirty-nine broilers, of which 35 noncolor marked, were housed in an experimental pen (1.80 × 2.61 m), and only data at 18 d of age were used. A YOLOv7-tiny model was trained (n = 140), validated (n = 30), and tested (n = 30) on 200 annotated frames to detect the broilers. On the test set, YOLOv7-tiny had a precision, recall, and average precision (@0.5 – Intersection over Union threshold) of 0.99. A multi-object tracker (SORT) was implemented and evaluated on ground-truth trajectories of thirteen white broilers based on 136 min of video data (1-min intervals). The number of ID-switches varied from 5 to 20 (mean: 9.92) per ground-truth trajectory, tracking times ranged from 1 (by definition) to 51 min (mean: 12.36), and tracking distances ranged from 0.01 to 17.07 meters (mean: 1.89) per tracklet. Tracking errors primarily occurred when broilers were occluded by the drinker, and relatively frequently when broilers were in close proximity (within 10 cm), with velocity and acceleration appearing to have a lesser impact on tracking errors. The study establishes a ‘baseline’ for future research and identified the potential and challenges of tracking group-housed individual broilers. The results highlighted the importance of addressing ID-switches, identified potential tracking algorithm improvements, and emphasized the need for an external animal identification system to enable objective, simultaneous and semi-continuous locomotion phenotyping of group-housed individual broilers.

Approximately 80% of the global cattle population is at risk of infestation and infection by ticks and tick-borne diseases (TTBDs). The economic losses from animal mortality, reduced production, vector control costs and animal treatment are very substantial, hence there is an urgent need to develop and deploy alternative vector control strategies. Breeding for host tick resistance has the potential for sustainable large-scale TTBD control especially in cattle. The gold standard method for phenotyping tick resistance in cattle is by counting ticks on the body but is very laborious and subjective. Better methods for phenotyping tick resistance more objectively, faster and at scale, are essential for selecting host genetic resistance to ticks. This study investigated the correlation between haematological cellular profiles and immunological responses (immunoglobulin E, IgE) and full body tick counts in herds of Bos indicus and Bos taurus following artificial tick challenge with Rhipicephalus decoloratus larvae. Fifty-four Friesian and Ayrshire (Bos taurus) and 52 East African Zebu (Bos indicus) calves were each infested with ∼2500 larvae. Near-replete adult female ticks (≥ 4.5 mm) were counted daily from Day 20–25. Blood and serum samples were obtained from each animal on Days 0 and 23 for cellular blood and IgE titre analysis, respectively. The indicine cattle were refractory to R. decoloratus infestation in comparison with the taurine breed (P

This study aimed to identify phenotypic and genotypic aminoglycoside and quinolone non-susceptibility and the prevalence of aminoglycoside-modifying enzymes and plasmid-mediated quinolone resistance genes among K. pneumoniae clinical isolates from northern Jordan. K. pneumoniae isolates (n = 183) were tested for antimicrobial susceptibility using the Kirby-Bauer disk diffusion method. The double-disk synergy test was used for the detection of the extended-spectrum beta-lactamase phenotype. Polymerase chain reaction was used to detect genes encoding aminoglycoside-modifying enzyme (aac (3′)-II, aac (6′)-II, aac (6′)-Ib, ant (3″)-I, aph (3′)-VI, armA, and rmtB), and plasmid-mediated quinolone resistance (qnrA, qnrB, qnrC, qnrD, qnrS, acc(6′)-Ib–cr, qepA, and oqxAB) genes. Multi-locus sequence typing was used to elucidate the genetic diversity of selected isolates. The non-susceptibility percentages to aminoglycosides and quinolones were 65.0 % and 61.7 %, respectively. The most frequent aminoglycoside-modifying enzyme gene was ant (3″)-I at 73.8 %, followed by aac (6′)-Ib at 25.1 %, aac (3′)-II at 17.5 %, aph (3′)-VI at 12.0 %, armA at 9.8 %, and rmtB at 0.5 %. Aac (6′)-II was not detected among the isolates. The most frequent plasmid-mediated quinolone resistance gene was oqxAB at 31.7 %, followed by qnrS at 26.2 %, qnrB at 25.7 %, and aac(6′)-Ib–cr at 25.7 %. QnrA, qnrD, qebA, and qnrC were not detected among the isolates. Aac (3′)-II, aac (6′)-Ib, aph (3′)-VI, armA, qnrB, qnrS, and acc(6′)-Ib–cr were significantly associated with non-susceptibility to aminoglycosides, quinolones, and beta-lactams. Among 27 randomly selected K. pneumoniae isolates, the most common sequence type was ST2096, followed by ST348 and ST1207. Overall, 19 sequence types were observed, confirming a high level of genetic diversity among the isolates. High percentages of non-susceptibility to the studied antimicrobials were found and were associated with the presence of several resistance genes. Similar studies should be periodically carried out to monitor changes in the prevalence of resistance phenotypes and genotypes of isolates.

الملخص: أهداف البحث: الزائفة الزنجارية، هو ممرض انتهازي يمكن أن يسبب العديد من التهابات المستشفيات. يساهم تكوين الأغشية الحيوية ومقاومة الأدوية والحركة في ضراوة الزائفة الزنجارية. يدرس هذا البحث الحد الأدنى من تركيز المثبط للكوليستين، وتكوين الأغشية الحيوية، ووجود جينات (مود أ) و (بسل أ) وأنواع الحركات في مقاومة الأدوية المتعددة والحساسية للأدوية المتعددة للزائفة الزنجارية. طريقة البحث: تمت دراسة 62 من الزائفة الزنجارية من القيح و 18 من عينات البول لقابليتها للمضادات الحيوية الشائعة الاستخدام، وتركيز الكوليستين المثبط الأدنى عن طريق تخفيف أجار والقدرة على تشكيل الأغشية الحيوية بواسطة طريقة لوحة عيار مكروي. تم اختبار جميع عزلات الزائفة الزنجارية المقاومة للأدوية المتعددة والحساسية للأدوية المتعددة لوجود جينات (مود أ) و (بسل أ) بواسطة مقايسة التفاعل السلسلي للبوليميراز وأنواع مختلفة من الحركات باستخدام وسائط معينة. النتائج: من بين 40 عزلة مقاومة للأدوية المتعددة و 40 عزلة متعددة الحساسية للأدوية ، كانت 17 عزلة مقاومة للكوليستين و 23 عزلة مقاومة متوسطة للكوليستين، على التوالي. أظهرت تسعة عزلات صديد مقاومة للأدوية وثلاث عزلات بول مقاومة للأدوية جميع الأنواع الثلاثة من القدرة على الحركة. أظهرت 13 عزلة صديد حساسة للأدوية و 4 عزلات بول متعددة الحساسية للأدوية كلا من حركة السباحة والتجمع. لم تظهر العزلات الحساسة للأدوية المتعددة حركية الوخز. كان هناك عدد أكبر من السلالات المقاومة للأدوية المتعددة منتجة قوية للأغشية الحيوية (عدد = 19) بينما كان عدد أكبر من السلالات المعرضة للأدوية المتعددة (عدد = 24) منتجة معتدلة للأغشية الحيوية. كانت سبعة وعشرون عزلة مقاومة للأدوية المتعددة و 28 عزلة حساسة للأدوية المتعددة إيجابية لكل من جينات (مود أ) و (بسل أ). من بين العزلات القوية المكونة للقيح الحيوي، عدد أكبر من العزلات المعرضة للأدوية المتعددة (عدد = 13) تحتوي على جينات (مود أ) و (بسل أ) عند مقارنتها بالعزلات متعددة الحساسية للأدوية. الاستنتاجات: تظهر النتائج التي توصلنا إليها بوضوح وجود علاقة ذات دلالة إحصائية بين تكوين الأغشية الحيوية القوية وجينات (مود أ) و (بسل أ) ومقاومة الأدوية في الزائفة الزنجارية المعزولة من العينات السريرية. من المستحسن إجراء دراسات إضافية لاستكشاف الجينات والعوامل الأخرى المسؤولة عن تكوين الأغشية الحيوية الضعيفة والمتوسطة ومقاومة الأدوية. Abstract: Objectives: Pseudomonas aeruginosa is an opportunistic pathogen that can cause many nosocomial infections. Biofilm formation, drug resistance, and motility contribute to virulence in P. aeruginosa. This study assessed the colistin minimum inhibitory concentration (MIC), biofilm formation, presence of mod A and psl A genes, and types of motilities in multidrug-resistant (MDR) and multidrug-susceptible (MDS) P. aeruginosa. Methods: Sixty-two P. aeruginosa from pus and 18 from urine samples were studied for their susceptibility to commonly used antibiotics, colistin MIC by agar dilution, and biofilm-forming ability by the microtiter plate method. All MDR and MDS P. aeruginosa isolates were tested for the presence of mod A and psl A genes by PCR, and different types of motilities using specific media. Results: Among the 40 MDR and 40 MDS isolates, 17 each were colistin-resistant and 23 each were colistin-intermediate. Nine MDR pus isolates and three MDR urine isolates showed all three types of motilities. Thirteen MDS pus isolates and four MDS urine isolates showed both swimming and swarming motility. MDS isolates did not show twitching motility. A higher number of MDR strains were strong biofilm producers (n = 19), whereas a higher number of MDS strains (n = 24) were moderate biofilm producers (p = 0.023). Twenty-seven MDR and twenty-eight MDS isolates were positive for both mod A and pslA genes. Among the strong biofilm-forming pus isolates, a greater number of MDR isolates (n = 13 each) had modA and pslA genes compared to MDS isolates (modA p = 0.017; pslA p = 0.014). Conclusions: Our findings clearly showed a statistically significant association among strong biofilm formation, modA, pslA genes, and drug resistance in P. aeruginosa isolated from clinical samples. Additional studies are needed to explore other genes and factors responsible for weak and moderate biofilm formation and drug resistance.

Introduction: Breast cancer (BC) is the most common type of cancer in premenopausal women with germline TP53 pathogenic variants (mTP53) (Li Fraumeni syndrome - LFS). However, little is known about the BC prognosis in these patients. This study analyzed the BC-related oncologic outcomes of patients with LFS. Methods: We evaluated a cohort of LFS patients with BC in comparison with a control cohort of BC patients with no pathogenic variant in a hereditary cancer panel. The primary endpoint was recurrence-free survival (RFS). Due to the risk of second malignancies in LFS, only locoregional and distant recurrences were considered events for RFS. Secondary endpoints included rates of contralateral BC, overall survival (OS), and breast cancer-specific survival (BCSS). Results: Forty-one patients were evaluated in the mTP53 group and 82 in the control group. Median age at BC diagnosis was 40 and 41 years, respectively. The mTP53 group received less adjuvant radiotherapy than the control group (63.4% vs 93.9%, P

Objectives:: In a previous study we reported that molecular profiling of bladder mucosal tissue from a modest number of IC/BPS patients resulted in a clear separation based on anesthetic bladder capacity (BC), with 400 cc representing the apparent breakpoint between low and non-low BC. The purpose of the current study was to revisit this earlier stratification finding, using a combination of molecular and clinical data, from a large and heterogeneous patient cohort. Materials and Methods:: To provide an updated assessment of IC/BPS patient stratification based on anesthetic BC, whole genome gene expression data from 48 mucosal biopsy samples (41 IC/BPS patients; 7 controls) were analyzed with unsupervised clustering and principal component analysis (PCA) to identify primary clusters of patients. This identified three primary individual clusters: (1) IC/BPS patients with a BC between 200–500 cc (n=19), (2) IC/BPS patients with a BC of 501–1500 cc (n=22), and (3) controls. Next, complete demographic, clinical, and questionnaire data prospectively collected from an additional 450 patients from our patient registry were used to conduct a combined analysis to verify this relationship. Characteristics of all 491 IC/BPS patients were compared between those having the current low BC cutoff (≤400 cc) and the proposed new cutoff (≤500 cc) by utilizing independent samples t-test (continuous variables) and chi square tests (categorical variables; p ≤ 0.05 was considered significant). Results:: A statistical comparison of the demographic and clinical characteristics of the entire 491 IC/BPS patient cohort showed that those with a bladder capacity ≤500 cc were older, were more likely to have Hunner lesions, and had higher symptom scores. This group also had a lower average number of non-urologic associated symptoms, pelvic pain syndromes, and neurologic, immune, or systemic pain syndromes. Conclusion:: By combining newly acquired molecular data with clinical and demographic characteristics in a large cohort of IC/BPS patients, we conclude that anesthetic BC ≤ 500 cc provides a clinically meaningful biomarker for the bladder centric IC/BPS phenotypic subgroup.

Objective: To investigate the variation in the distribution and the natural history of hand pain over 6 weeks in individuals with symptomatic hand osteoarthritis. Design: Patient-reported outcome data were collected at baseline and weekly for 6 weeks from community-based participants enrolled in a randomised controlled trial. Participants were grouped based on location of significant pain (Visual Analogue Scale, VAS≥40/100 ​mm) (both carpometacarpal (CMC) and interphalangeal (IP), CMC only, and IP only). Results: At baseline, of the 106 participants, 55(51.9 %) had pain in both CMC and IP joints, 28(26.4 %) in IP joints only, and 16(15.1 %) in CMC joint only. Those with CMC and IP pain had significantly higher VAS pain [68.1 (2.6) vs 59.3 (3.5) vs 51.2 (4.7)]; Australian Canadian Osteoarthritis Hand Index, (AUSCAN) pain [290.1 (15.7) vs 225.3 (21.2) vs 237.9 (28.4)], stiffness [57.1 (3.7) vs 44.6 (5.0) vs 32.2 (6.7)] and functional limitation [527.5 (30.9) vs 356.0 (41.7) vs 433.3 (55.7)]; and pain sensitization [PainDETECT score 11.1 (1.1) vs 8.1 (1.8) vs 5.8 (1.9)] compared to those with IP or CMC only pain, respectively. All groups showed improvement in outcomes over 6 weeks without significant inter-group differences. Conclusion: In a population with significant hand pain, pain in both CMC and IP joints was most common and identified a more severe phenotype than pain in IP or CMC only with higher pain, more functional limitation and pain sensitization. These data have the potential to inform clinical management of patients with hand pain and patient selection in clinical trials.

Summary: Background: Identifying phenotypes in sepsis patients may enable precision medicine approaches. However, the generalisability of these phenotypes to specific patient populations is unclear. Given that paediatric cancer patients with sepsis have different host response and pathogen profiles and higher mortality rates when compared to non-cancer patients, we determined whether unique, reproducible, and clinically-relevant sepsis phenotypes exist in this specific patient population. Methods: We studied patients with underlying malignancies admitted with sepsis to one of 25 paediatric intensive care units (PICUs) participating in two large, multi-centre, observational cohorts from the European SCOTER study (n = 383 patients; study period between January 1, 2018 and January 1, 2020) and the U.S. Novel Data-Driven Sepsis Phenotypes in Children study (n = 1898 patients; study period between January 1, 2012 and January 1, 2018). We independently used latent class analysis (LCA) in both cohorts to identify phenotypes using demographic, clinical, and laboratory data from the first 24 h of PICU admission. We then tested the association of the phenotypes with clinical outcomes in both cohorts. Findings: LCA identified two distinct phenotypes that were comparable across both cohorts. Phenotype 1 was characterised by lower serum bicarbonate and albumin, markedly increased lactate and hepatic, renal, and coagulation abnormalities when compared to phenotype 2. Patients with phenotype 1 had a higher 90-day mortality (European cohort 29.2% versus 13.4%, U.S. cohort 27.3% versus 11.4%, p

Objectives: Modified form of VISTA (MVISTA), a novel surgical procedure, aims at comprehensive root coverage that maintains the inner continuity of the periosteum and papilla. This technique incorporates any regenerative graft material within the tunnel. The objective of study is to compare the MVISTA for treating multiple adjacent gingival recessions and chorion membranes or grafts of connective tissues. Materials and methods: This is a split-mouth type randomized trial. In this trial total of 18 patients were considered. The patients in this trial had multiple adjacent, gingival recessions of Miller's Classes I/II, and they were randomized to either the MVISTA with chorion membrane (test) or connective tissue graft (CTG) (control) group. A baseline and one year after surgery were considered for recording to mean root coverage (MRC), complete root coverage (CRC), and clinical periodontal parameters. An intragroup comparison was made. Results: The intragroup comparison of recession depth baseline and 12 months after-surgery record found a significant difference between the two groups (P = 0.00). In the postoperative condition, the depth of recession reduction was higher in the test group than in the control group. However, from a statistical perspective, the difference was insignificant (P > 0.05). At the end of the year, it was found that the width of the keratinized tissue had increased significantly (P 000). At the end of 1 year, the test group showed 66.67 % CRC compared to 44.44 % in the control group. The gingival phenotype displayed statistically significant improvement in the test group (p = 0.004). PD and CAL showed statistically nonsignificant outcomes (P > 0.05). Conclusions: As far as multiple adjacent gingival recession treatment is concerned, MVISTA with chorion membrane treatment enhanced the gingival phenotype, restored complete root coverage (66.6%), and increased the width of keratinized tissue. CTG and CM demonstrated good root coverage results; the latter might be used as a substitute graft to treat multiple recessions.

Background: Asthma is a heterogeneous disease, and phenotyping can facilitate understanding of disease pathogenesis and direct appropriate asthma treatment. This nationwide cohort study aimed to phenotype asthma patients in Japan and identify potential biomarkers to classify the phenotypes. Methods: Adult asthma patients (n = 1925) from 27 national hospitals in Japan were enrolled and divided into Global Initiative for Asthma (GINA) steps 4 or 5 (GINA 4, 5) and GINA Steps 1, 2, or 3 (GINA 1–3) for therapy. Clinical data and questionnaires were collected. Biomarker levels among GINA 4, 5 patients were measured. Ward's minimum variance hierarchical clustering method and tree analysis were performed for phenotyping. Analysis of variance, the Kruskal–Wallis, and chi-square tests were used to compare cluster differences. Results: The following five clusters were identified: 1) late-onset, old, less-atopic; 2) late-onset, old, eosinophilic, low FEV1; 3) early-onset, long-duration, atopic, poorly controlled; 4) early-onset, young, female-dominant, atopic; and 5) female-dominant, T1/T2-mixed, most severe. Age of onset, disease duration, blood eosinophils and neutrophils, asthma control questionnaire Sum 6, number of controllers, FEV1, body mass index (BMI), and hypertension were the phenotype-classifying variables determined by tree analysis that assigned 79.5% to the appropriate cluster. Among the cytokines measured, IL-1RA, YKL40/CHI3L1, IP-10/CXCL10, RANTES/CCL5, and TIMP-1 were useful biomarkers for classifying GINA 4, 5 phenotypes. Conclusions: Five distinct phenotypes were identified for moderate to severe asthma and may be classified using clinical and molecular variables (Registered in UMIN-CTR; UMIN000027776.)

Background: Eczema patients are commonly immunoglobulin (Ig)E polysensitized. Although atopic dermatitis (AD) phenotypes have been recognized, IgE sensitization patterns based on AD phenotypes have not been well illustrated. We aimed to investigate how eczema phenotypes impact IgE component sensitization patterns. Methods: This birth cohort study investigated a general population in the Tokyo Children's Health, Illness, and Development Study (T-Child Study) until children reached the age of 13 years. Eczema was assessed using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Allergen component specific IgE antibody titers were measured using a multiplex array ImmunoCAP ISAC. Results: Persistent eczema phenotype until adolescence was strongly associated with allergic march symptoms, such as wheezing and hay fever, and oral allergy symptoms, and IgE component sensitizations of airborne (Japanese cedar, house dust mite, Timothy, cat, and dog) and cross-reactive allergens (Bet v 1 family) compared to early-remission and late-onset eczema. On the other hand, late-onset eczema did not show any strong associations with allergic symptoms and IgE sensitization. Adolescents with persistent eczema have high comorbidity of symptoms of pollen-food allergy syndrome. Conclusions: Early-onset eczema is deeply connected with the later allergic march, and late-onset eczema differs from the phenotype of allergic march. Early-onset eczema characterizing IgE sensitization was likely to be an extrinsic type, and late-onset eczema, which was not related to IgE sensitization, was likely an intrinsic type. Pollen-Food Allergy Syndrome is one of the allergic features in allergic march.

Asthma is a syndrome with extremely diverse clinical phenotypes in which the onset, severity, and response to treatment are defined by the complex interplay of many genetic and environmental factors. Environmental factors epigenetically affect gene expression, and the disease is driven by a multidimensional dynamic network involving RNA and protein molecules derived from gene expression, as well as various metabolic products. In other words, specific pathophysiological mechanisms or endotypes are dynamic networks that arise in response to individual genotypes and the various environmental factors to which individuals have been exposed since before birth, such as diet, infection, air pollution, smoking, antibiotic use, and the bacterial flora of the intestinal tract, skin, and lungs. A key feature of asthma genome scans is their potential to reveal the molecular pathways that lead to pathogenesis. Endotypes that drive the disease have a significant impact on the phenotypes of asthma patients, including their drug responsiveness. Understanding endotypes will lead to not only the implementation of therapies that are tailored to the specific molecular network(s) underlying the patient's condition, but also to the development of therapeutic strategies that target individual endotypes, as well as to precision health, which will enable the prediction of disease onset with high accuracy from an early stage and the implementation of preventive strategies based on endotypes. Understanding of endotypes will pave the way for the practice of precision medicine in asthma care, moving away from ‘one-size-fits-all’ medicine and population-based prevention approaches that do not take individuals' susceptibility into account.

Objective: To assess the predictive value of selected growth phenotypes for neonatal morbidity and mortality in preterm infants < 30 weeks and to compare them with INTERGROWTH-21st (IG21). Method: Retrospective analysis of data from the Brazilian Neonatal Research Network (BNRN) database for very low birth weight (VLBW) at 20 public tertiary-care university hospitals. Outcome: the composite neonatal morbidity and mortality (CNMM) consisted of in-hospital death, oxygen use at 36 weeks, intraventricular hemorrhage grade 3 or 4, and Bell stage 2 or 3 necrotizing enterocolitis. Selected growth phenotypes: small-for-gestational-age (SGA) defined as being < 3rd (SGA3) or 10th (SGA10) percentiles of BW, and large-for-gestational-age (LGA) as being > 97th percentile of BW. Stunting as being < 3rd percentile of the length and wasting as being < 3rd percentile of BMI. Single and multiple log-binomial regression models were fitted to estimate the relative risks of CNMM, comparing them to IG21. Results: 4,072 infants were included. The adjusted relative risks of CNMM associated with selected growth phenotypes were (BNRN/IG21): 1.45 (0.92–2.31)/1.60 (1.27–2.02) for SGA; 0.90 (0.55–1.47)/1.05 (0.55–1.99) for LGA; 1.65 (1.08–2.51)/1.58 (1.28–1.96) for stunting; and 1.48 (1.02–2.17) for wasting. Agreement between the two references was variable. The growth phenotypes had good specificity (>95%) and positive predictive value (70-90%), with poor sensitivity and low negative predictive value. Conclusion: The BNRN phenotypes at birth differed markedly from the IG21 standard and showed poor accuracy in predicting adverse neonatal outcomes.

Backgrounds: Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) are emerging worldwide. The optimal treatment for CRKP infections is challenging for clinicians because therapeutic agents are greatly limited. Material and methods: A retrospective study of CRKP monomicrobial bacteremia was conducted at a medical center between 2010 and 2016. The use of at least one or more drugs with in vitro activity against the blood isolates was defined as appropriate combination therapy. The logistic regression model and propensity score analysis was used to assess clinical effects of therapeutic strategies. The 30-day crude mortality was the primary end point. Results: Two hundred and three patients were eligible and the 30-day mortality rate was 37.9% (77 patients). As compared with monotherapy, empirical (11.6 vs. 57.3%, p

In aquatic animals, microbial communities associated with the host exert powerful influences on physiology, reproduction, nutrient metabolism, and phenotypic traits, as well as complex host behaviors. This relationship between host and microbes suggests that host-microbiota interactions might have influenced the host's genetic and phenotypic variation. To improve our understanding of how microbes and hosts interact and produce phenotypes, it is necessary to focus on animal phenotypic traits as a basis to understand the potential roles for the microbiome in shaping host phenotypes. Here, we review the literatures on the influences of host genetic and environmental effects on intestinal microbial community structure, and corresponding effects of microbiomes on aquatic animal host phenotypes and genetic breeding. This review provides a better understanding of how the gut microbiota establishes a connection with host genetic factors, while modulating the intestinal microbiota to affect phenotypic differentiation. A more detailed understanding of how the microbiota influences host phenotypes might contribute to determining the role of gut microbiota in the field of genetic breeding of aquatic animals.

Objective: Polycystic ovarian syndrome (PCOS) is a metabolic syndrome in which steroidogenesis, folliculogenesis, and cellular adhesion play crucial roles in its prognosis. These pathways are controlled and regulated by some small non-coding RNAs called microRNAs (miRs). Several miRs have differential expression in PCOS compared to healthy women, and their dysregulation suggests important roles of miRs in PCOS pathophysiology. However, the role of miRs is still unclear, especially in various phenotypes of PCOS. Materials and methods: This study was conducted to evaluate the diagnostic potential of miR-212-3p, miR-490-5p, miR-647, and miR-4643 in different subtypes of PCOS. Accordingly, nineteen PCOS patients with different subtypes based on Rotterdam criteria (A: 8, B: not detected in this study, C: 5, and D: 6 patients) and six control age and BMI matched women under ICSI treatment were selected. The relative expression of miRs was then measured in blood serum before hormonal treatment (S1) and before ovum pickup (S2), follicular fluid (FF), and cumulus cells (CC) in all subjects. Also, the expression of miRs predicted target genes (AMH, AR, CYP11A1, CYP17A1, CYP19A1, GDF9, and HSD17B12) were done in the CC of understudy groups. Results: In general, the results indicated that PCOS significantly increased the expression of miR-212-3p, miR-490-5p, and miR-4643 in FF and CCs compared to control. Although these miRs tend to increase in serum 1 of the PCOS patients, the differences were insignificant. However, there was a significant reduction in the expression of miR-647 in FF and CCs between PCOS vs. control. In addition, the miRs had significantly different expressions in various phenotypes of PCOS. For example, high levels of miR-647 in S2 and low levels of miR-490 in FF and miR-212 in CC can differentiate phenotype A from the other. Also, upregulation of miR-212 in FF and miR-4643 in S1 and low levels of this miR in FF can specifically differentiate subtype A from D. On the other hand, high levels of miR-4643 in FF and miR-490 in CC and lower titter of miR-647 can distinguish subtype C from the other. On the other hand, high levels of AMH, AR, CYP11, CYP17, and HSD17 in the hyperandrogenic PCOS and upregulation of CYP19A1 in the hypoandrogenic group can validate the role of selected miRs in the prognosis of PCOS. Conclusion: Characterization of altered microRNAs in serum, FF, and CCs and their targets in CC showed that the miRs might play critical roles in steroidogenesis and folliculogenesis. These miRs may be used for molecular classification of PCOS subtypes and as biomarkers for PCOS diagnosis.

ABSTRACT: There is growing evidence that animal personality is linked to a range of productivity traits in farm animals, including dairy cattle. To date, the methodology for assessing personality traits of dairy cattle is time consuming and often requires a test arena, which limits the opportunity for commercial farms to use personality traits of dairy cattle for individualized management. This study investigated whether personality traits of pastured dairy cattle, scored in short behavioral tests, are associated with daily behavioral patterns and milk production. Cows (n = 87) were exposed twice to each of 5 behavioral tests, where their responses to novel or putatively stressful situations were scored on an ordinal scale for investigative and reactive behavior toward a novel object and a novel human after exiting the milking parlor, response to restraint in a crush, avoidance distance from an approaching human in the paddock, and response to milking (step-kick behavior). Most behavior test scores were consistent over the 2 test repeats (using repeatability estimates, Mann-Whitney U test of difference between repeats, and Spearman rank correlation). Behavior test scores were subjected to a principal components analysis that revealed intertest relationships in 3 factors of correlated sets of test scores, interpreted as personality traits (fearful of humans, calm-investigative, and reactive to milking). Regression analyses determined how these traits were associated with daily grazing, ruminating, and lying behaviors, and milk production (after controlling for cow age, breed, lactation status, group, and climate variables). Cows that were more fearful of humans (high avoidance distance, reactive toward the novel human) had reduced lying time compared with cows that scored low on this trait. Cows that were more calm (during restraint) and investigative (toward the novel object) had greater grazing time, which likely contributed to their greater milk production compared with cows that scored low on this trait. Cows that were more reactive to milking produced less milk than cows that scored low on this trait. These results indicate that individual differences in daily behavior patterns and milk production of dairy cattle are associated with personality traits of cows, measured using several short behavioral tests. These methods may be useful for characterizing grazing dairy cattle on commercial farms, which could aid in understanding individual behavior patterns and provide opportunities for individualized management.

Abstract Background Gaining insight into crop diversity, both at the genetic and phenotypic levels, is of prime importance for onion breeding with an enhanced yield and quality in combination with improved resistance to biotic and abiotic stresses. In the current study, 192 different onion plants, representing 16 ecotypes, were characterized using ISSR markers. Results Based on the ISSR marker profile, there was a clear grouping of the plants into 16 different ecotypes. Though the 16 populations originated from the same geographic region in Morocco, a significant genetic diversity was detected. After a genomic characterization, field trials in three different environments in Morocco were laid out. The phenotypic characterization showed that there were always significant differences between ecotypes, and for most traits, there was also a significant environmental effect and a significant interaction between environment and ecotype. The broad-sense heritability (H 2) for the phenotypic traits associated with color (L*, a*, and b*) was the largest (84.2%, 80.6%, 79.2%), demonstrating that color is conditioned primarily by genetic factors. In contrast, the H 2 for yield was the lowest (41.8%), indicating that the environment has a substantial effect on yield. In addition, there was a significant association between the presence/absence of certain bands and various phenotypic traits. Conclusion ISSR markers are a powerful tool in distinguishing onion ecotypes. In addition, significant associations between marker scores and phenotypic traits could be detected, representing particular importance for future breeding programs.

ABSTRACT: Background: Degenerative disc disease, a major cause of low back pain and associated neurological symptoms, is a global health problem with the high morbidity, workforce loss, and socioeconomic burden. The present surgical strategy of disc resection and/or spinal fusion results in the functional loss of load, shock absorption, and movement; therefore, the development of new biological therapies is demanded. This achievement requires the understanding of intervertebral disc cell fate during aging and degeneration. Methods: Literature review was performed to clarify the current concepts and future perspectives of disc cell fate, focused on apoptosis, senescence, and autophagy. Results: The intervertebral disc has a complex structure with the nucleus pulposus (NP), annulus fibrosus (AF), and cartilage endplates. While the AF arises from the mesenchyme, the NP originates from the notochord. Human disc NP notochordal phenotype disappears in adolescence, accompanied with cell death induction and chondrocyte proliferation. Discs morphologically and biochemically degenerate from early childhood as well, thereby suggesting a possible involvement of cell fate including age-related phenotypic changes in the disease process. As the disc is the largest avascular organ in the body, nutrient deprivation is a suspected contributor to degeneration. During aging and degeneration, disc cells undergo senescence, irreversible growth arrest, producing proinflammatory cytokines and matrix-degradative enzymes. Excessive stress ultimately leads to programmed cell death including apoptosis, necroptosis, pyroptosis, and ferroptosis. Autophagy, the intracellular degradation and recycling system, plays a role in maintaining cell homeostasis. While the incidence of apoptosis and senescence increases with age and degeneration severity, autophagy can be activated earlier, in response to limited nutrition and inflammation, but impaired in aged, degenerated discs. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is a signal integrator to determine disc cell fate. Conclusions: Cell fate and microenvironmental regulation by modulating PI3K/Akt/mTOR signaling is a potential biological treatment for degenerative disc disease.

The integrated rice-crayfish culture (IRCC) mode has been developed for more than twenty years in China, but little information could be obtained on the microbial communities in paddy soil under this mode. This study used 16SrRNA and ITS Illumina high-throughput sequencing to investigate microbial communities, diversity, and function in paddy soil under different IRCC times (0, 2, 4, 6, and 10 years). With increasing culture time, IRCC mode altered the relative abundance of dominant taxa, showing a significant decrease in the relative abundance of Actinobacteria and Chytridiomycota, with an increase in Proteobacteria and Firmicutes. The species richness and diversity of bacteria/fungi in 10-year IRCC paddy soil were significantly lower than in other groups (P