First-principles investigations of the controllable electronic properties and contact types of type II MoTe2/MoS2 van der Waals heterostructures.

Two-dimensional (2D) van der Waals (vdW) heterostructures are considered as promising candidates for realizing multifunctional applications, including photodetectors, field effect transistors and solar cells. In this work, we performed first-principles calculations to design a 2D vdW MoTe2/MoS2 heterostructure and investigate its electronic properties, contact types and the impact of an electric field and in-plane biaxial strain. We find that the MoTe2/MoS2 heterostructure is predicted to be structurally, thermally and mechanically stable. It is obvious that the weak vdW interactions are mainly dominated at the interface of the MoTe2/MoS2 heterostructure and thus it can be synthesized in recent experiments by the transfer method or chemical vapor deposition. The construction of the vdW MoTe2/MoS2 heterostructure forms a staggered type II band alignment, effectively separating the electrons and holes at the interface and thereby extending the carrier lifetime. Interestingly, the electronic properties and contact types of the type II vdW MoTe2/MoS2 heterostructure can be tailored under the application of external conditions, including an electric field and in-plane biaxial strain. The semiconductor-semimetal-metal transition and type II-type I conversion can be achieved in the vdW MoTe2/MoS2 heterostructure. Our findings underscore the potential of the vdW MoTe2/MoS2 heterostructure for the design and fabrication of multifunctional applications, including electronics and optoelectronics.

Novel Semi-Nested Real-Time PCR Assay Leveraging Extendable Blocking Probes for Improved SHOX2 Methylation Analysis in Lung Cancer.

Lung cancer is the leading cause of cancer deaths globally, necessitating effective early detection methods. Traditional diagnostics like low-dose computed tomography (LDCT) often yield high false positive rates. SHOX2 gene methylation has emerged as a promising biomarker. This study aimed to develop and validate a novel semi-nested real-time PCR assay enhancing sensitivity and specificity for detecting SHOX2 methylation using extendable blocking probes (ExBPs). The assay integrates a semi-nested PCR approach with ExBPs, enhancing the detection of low-abundance methylated SHOX2 DNA amidst unmethylated sequences. It was tested on spiked samples with varied methylation levels and on clinical samples from lung cancer patients and individuals with benign lung conditions. The assay detected methylated SHOX2 DNA down to 0.01%. Clinical evaluations confirmed its ability to effectively differentiate between lung cancer patients and those with benign conditions, demonstrating enhanced sensitivity and specificity. The use of ExBPs minimized non-target sequence amplification, crucial for reducing false positives. The novel semi-nested real-time PCR assay offers a cost-effective, highly sensitive, and specific method for detecting SHOX2 methylation, enhancing early lung cancer detection and monitoring, particularly valuable in resource-limited settings.

An EEG & eye-tracking dataset of ALS patients & healthy people during eye-tracking-based spelling system usage.

This research presents a dataset consisting of electroencephalogram and eye tracking recordings obtained from six patients with amyotrophic lateral sclerosis (ALS) in a locked-in state and one hundred seventy healthy individuals. The ALS patients exhibited varying degrees of disease progression, ranging from partial mobility and weakened speech to complete paralysis and loss of speech. Despite these physical impairments, the ALS patients retained good eye function, which allowed them to use a virtual keyboard for communication. Data from ALS patients was recorded multiple times at their homes, while data from healthy individuals was recorded once in a laboratory setting. For each data recording, the experimental design involved nine recording sessions per participant, each corresponding to a common human action or demand. This dataset can serve as a valuable benchmark for several applications, such as improving spelling systems with brain-computer interfaces, investigating motor imagination, exploring motor cortex function, monitoring motor impairment progress in patients undergoing rehabilitation, and studying the effects of ALS on cognitive and motor processes.

Evaluating the safety of high-intensity focused ultrasound treatment for rectal endometriosis: results from a French prospective multicentre study including 60 patients.

STUDY QUESTION: Is increasing the intensity of high-intensity focused ultrasound (HIFU) by 30% in the treatment of rectal endometriosis a safe procedure? SUMMARY ANSWER: This study demonstrates the safety of a 30% increase in the intensity of HIFU in the treatment of rectal endometriosis, with no Clavien-Dindo Grade III complications overall, and namely no rectovaginal fistulae. WHAT IS KNOWN ALREADY: A feasibility study including 20 patients with rectal endometriosis demonstrated, with no severe complications, a significant improvement in digestive disorders, dysmenorrhoea, dyspareunia, and health status, although the volume of the endometriosis nodule did not appear to be reduced. STUDY DESIGN, SIZE, DURATION: A prospective multicentre cohort study was conducted between 2020 and 2022 with 60 patients with symptomatic rectal endometriosis. Following the failure of medical treatment, HIFU treatment was offered as an alternative to surgery. PARTICIPANTS/MATERIALS, SETTING, METHODS: As the main objective of this study was to examine safety, all adverse events observed during the 6 months of follow-up were analysed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) and Clavien-Dindo classifications. Secondary objectives included evaluating the evolution of symptoms using validated questionnaires: gynaecological and digestive pain symptoms with a visual analogue scale, health status with the Medical Outcomes Study 36-item Short Form (SF-36) questionnaire, average post-operative daily pain level, and analgesic medication required in the 10 days following treatment. MRI was also performed at Day 1 to detect early complications. Finally, we performed a blinded MRI review of the evolution of the nodule at 6 months post-treatment. MAIN RESULTS AND THE ROLE OF CHANCE: The procedure was performed under spinal anaesthesia for 30% of the patients. The median duration of treatment was 32 min. Fifty-five patients left the hospital on Day 1. MRI scans performed on Day 1 did not highlight any early-onset post-operative complication. Using the Clavien-Dindo classification, we listed 56.7% Grade I events, 3.4% Grade II events, and no events Grade III or higher. At 1, 3, and 6 months, all gynaecologic, digestive and general symptoms, as well as health status, had significantly improved. The evolution of the nodule was also significant (P < 0.001) with a 28% decrease in volume. LIMITATIONS, REASONS FOR CAUTION: The main objective was safety and not effectiveness. The study was not randomized and there was no control group. WIDER IMPLICATIONS OF THE FINDINGS: HIFU treatment for rectal endometriosis results in an improvement of symptoms with low morbidity; as such, for selected patients, it could be a valuable alternative to surgical approaches following the failure of medical treatment. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the company EDAP TMS. Professors Dubernard and Rousset are consultants for EDAP TMS. Dubernard received travel support from EDAP-TMS. Dr F. Chavrier received industrial grants from EDAP-TMS. He has developed a device for generating focused ultrasonic waves with reduced treatment time. This device has been patented by EDAP-TMS. Dr Lafon received industrial grants from EDAP-TMS; he declares that EDAP-TMS provided funding directly to INSERM to support a young researcher chair in therapeutic ultrasound, which is unrelated to the current study. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT04494568.

A20 promoted the phagocytosis of lymphoma cells by dendritic cells from activated B-cell-like non-Hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) is a lymphoproliferative disorder derived from either B or T lymphocytes. Among NHL, activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) and T cell non-Hodgkin lymphomas (T-NHL) are poor prognosis and aggressive subtypes. Macrophages are professional phagocytic cells and dendritic cells (DCs) are professional antigen-presenting cells in immune system. Doxorubicin (Dox) and Etoposide (ET) are the most effective anti-cancer drugs. A20 and CYLD are negative regulators of NF-κB-dependent functions in many cell types. Little is known about the roles of A20 and CYLD in regulating functions of DCs and macrophages from NHL. The present study, therefore, explored whether A20/CYLD expression contributes to functions of DCs and macrophages from NHL. To this end, blood samples of seventy-nine patients with ABC DLBCL and T-NHL were examined. Gene expression profile was determined by quantitative RT-PCR and immunophenotype, cell apoptosis and phagocytosis by flow cytometry. As a result, immunophenotypic analysis showed that the numbers of CD13+CD117-, CD56+CD40+ and CD23+CD40+ expressing cells were significantly elevated in ABC DLBCL cases compared to healthy individuals and T-NHL patients. Interestingly, upon treatment of Dox and ET, the phagocytosis of lymphoma cells was significantly reduced by CD11c+CD123- DCs and the percentage of CD56+ mature DCs was significantly enhanced in ABC DLBCL patients only in the presence of A20 siRNA, but not CYLD siRNA. In conclusion, ABC DLBCL patients with low A20 expression were defective in elimination of lymphoma cells by DCs and linked to killer DC expansion in circulation.

Minimum information and guidelines for reporting a multiplexed assay of variant effect.

Multiplexed assays of variant effect (MAVEs) have emerged as a powerful approach for interrogating thousands of genetic variants in a single experiment. The flexibility and widespread adoption of these techniques across diverse disciplines have led to a heterogeneous mix of data formats and descriptions, which complicates the downstream use of the resulting datasets. To address these issues and promote reproducibility and reuse of MAVE data, we define a set of minimum information standards for MAVE data and metadata and outline a controlled vocabulary aligned with established biomedical ontologies for describing these experimental designs.

Do research collaborations age like wine? Absolute and relative measures of CANZUK research partnerships' strength since the 1950s.

Although previous studies of today's globalised and competitive research landscape have mentioned the research collaborations of CANZUK countries (i.e., Australia, Canada, New Zealand, and the United Kingdom), none have yet studied them in detail. Further, such studies have used different measures of international research collaboration (IRC), resulting in disparate findings. This paper, therefore, analyses the strengths of CANZUK research collaborations, how those collaborations have changed over time, and assesses the effect of three ways of measures on the results (absolute strength, bilateral similarity, and multilateral similarity). We provide a detailed characterisation of the CANZUK research network and its relationships with partner countries, which reveals that the most collaborative CANZUK countries are the UK and Australia, among other findings. We also confirm that many findings differ depending on which measures are used. We offer an explanation of this difference with reference to the nature of the measures (i.e., what they really measure) and make suggestions for suitable measures in future studies depending on their purpose. Finally, we discuss how this study's findings can be used by research policy makers (in CANZUK and elsewhere) in deciding on research strategy and by researchers in appropriately measuring IRC.

Multi-Modality Imaging in Vasculitis.

Systemic vasculitides are a rare and complex group of diseases that can affect multiple organ systems. Clinically, presentation may be vague and non-specific and as such, diagnosis and subsequent management are challenging. These entities are typically classified by the size of vessel involved, including large-vessel vasculitis (giant cell arteritis, Takayasu's arteritis, and clinically isolated aortitis), medium-vessel vasculitis (including polyarteritis nodosa and Kawasaki disease), and small-vessel vasculitis (granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis). There are also other systemic vasculitides that do not fit in to these categories, such as Behcet's disease, Cogan syndrome, and IgG4-related disease. Advances in medical imaging modalities have revolutionized the approach to diagnosis of these diseases. Specifically, color Doppler ultrasound, computed tomography and angiography, magnetic resonance imaging, positron emission tomography, or invasive catheterization as indicated have become fundamental in the work up of any patient with suspected systemic or localized vasculitis. This review presents the key diagnostic imaging modalities and their clinical utility in the evaluation of systemic vasculitis.

[Laparoscopic ultrasound-guided radiofrequency ablation of uterine fibroid: A retrospective study]. / Myolyse des fibromes utérins par radiofréquence cœlioscopique sous contrôle échographique : à propos d'une série rétrospective.

OBJECTIVE: To assess clinical and radiological efficacy and safety of laparoscopic ultrasound-guided radiofrequency ablation of uterine leiomyomas. MATERIAL AND METHODS: Thirty-three patients with symptomatic uterine leiomyomas FIGO type 2 to 7, have undergone a laparoscopic ultrasound-guided radiofrequency ablation at Croix Rousse University Hospital Center (Hospices civils de Lyon) and at Saint-Vincent de Paul Hospital in Lille, between June 2020 and December 2022. The characteristics of each myoma and the symptoms were assessed with pelvic MRI and with Higham score, SSS and HRQL scores preoperatively and at 6 months. RESULTS: A total of 54 fibroids have been treated in 33 patients. We observed a significant decrease of the volume 6 months after the surgery, on average 21mL (55.97 vs. 74.37mL, 95% CI [7.13-34.88], P=0.001). The maximum diameter of each fibroid was also significantly reduced on average 11.78mm (41.89 vs. 52.06, 95% CI [8.83-14.73], P<0.05). We noticed a significant decrease of the NRS for dysmenorrhea on average 2.79 points (2.1 vs. 4.89, 95% CI [1.14-4.42], P<0.05). There was also a trend to improvement of menorrhagia, assess by Higham score. Indeed, 70.8% of the patients had menorrhagia. Menorrhagia was improved of 108,3 points with an average Higham score before surgery of 197.3 versus 87.9 after surgery (95% CI [47.9-168.8], P=0.001). Concerning UFS-QOL score: the symptom severity score (SSS) decreased on average 33 points, testifying of symptom improvement (27.04 vs. 60.89, 95% CI [22.92-43.39], P<0.001) and the HRQL score increased on average 20 points testifying quality of life improvement (65.57 vs. 42.7, 95% CI [15.83-37.85]. P<0.001). No severe adverse event has been reported. CONCLUSION: In this first French study about radiofrequency ablation. We confirm its efficiency for improvement of symptoms and quality of life but other study is mandatory to confirm the safety of this procedure in particular in patients with a wish to conceive.

Modification of graphene oxide and its effect on properties of natural rubber/graphene oxide nanocomposites.

Modification of graphene oxide (GO) by vinyltriethoxysilane (VTES) was investigated to study the effect of silanized GO on radical graft copolymerization of GO onto deproteinized natural rubber (DPNR). The modified GO, GO-VTES (a and b), was characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy, contact angle, thermal gravimetric analysis, and scanning electron microscopy. The XRD results showed the appearance of an amorphous region of silica particles at a diffraction angle of 22°. The formation of silica was investigated by 29Si NMR, and it was found that the hydrolysis and condensation of VTES proceed more completely in basic conditions than in acidic conditions. The silica content of GO-VTES(b) was 43%, which is higher than that of GO-VTES(a) (8%). Morphology of silica was observed by SEM. The DPNR/GO-VTES nanocomposites prepared with the same amount of GO, GO-VTES(a), and GO-VTES(b) were characterized with tensile tests and dynamic mechanical tests. The stress at break of DPNR/GO-VTES(a) and DPNR/GO-VTES(b) was 5.2 MPa and 4.3 MPa, respectively, which were lower than that of DPNR/GO. However, it exhibited higher stress at small strains and higher storage modulus than DPNR/GO.

Association of UGT1A1 gene variants, expression levels, and enzyme concentrations with 2,3,7,8-TCDD exposure in individuals exposed to Agent Orange/Dioxin.

Among the congener of dioxin, 2,3,7,8-TCDD is the most toxic, having a serious long-term impact on the environment and human health. UDP-glucuronosyltransferase 1A1 (UGT1A1) plays a crucial role in the detoxification and excretion of endogenous and exogenous lipophilic compounds, primarily in the liver and gastrointestinal tract. This study aimed to investigate the association of UGT1A1 gene polymorphisms, expression levels, and enzyme concentration with Agent Orange/Dioxin exposure. The study included 100 individuals exposed to Agent Orange/Dioxin nearby Da Nang and Bien Hoa airports in Vietnam and 100 healthy controls. UGT1A1 SNP rs10929303, rs1042640 and rs8330 were determined by Sanger sequencing, mRNA expression was quantified by RT-qPCR and plasma UGT1A1 concentrations were measured by ELISA. The results showed that UGT1A1 polymorphisms at SNPs rs10929303, rs1042640 and rs8330 were associated with Agent Orange/Dioxin exposure (OR = 0.55, P = 0.018; OR = 0.55, P = 0.018 and OR = 0.57, P = 0.026, respectively). UGT1A1 mRNA expression levels and enzyme concentration were significantly elevated in individuals exposed to Agent Orange/Dioxin compared to controls (P < 0.0001). Benchmark dose (BMD) analyses showed that chronic exposure to 2,3,7,8-TCDD contamination affects the UGT1A1 mRNA and protein levels. Furthermore, UGT1A1 polymorphisms affected gene expression and enzyme concentrations in individuals exposed to Agent Orange/Dioxin. In conclusion, UGT1A1 gene polymorphisms, UGT1A gene expression levels and UGT1A1 enzyme concentrations were associated with Agent Orange/Dioxin exposure. The metabolism of 2,3,7,8-TCDD may influence UGT1A gene expression and enzyme concentrations.

Dynamic Visualization of DNA Methylation in Cell Cycle Genes during iPSC Cardiac Differentiation.

Background: Epigenetic DNA methylation is an essential mechanism controlling gene expression and cellular function. Existing analyses with conventional assays have generated significant insights into static states of DNA methylation, but were unable to visualize the dynamics of epigenetic regulation. Aim: We utilized a genomic DNA methylation reporter (GMR) system to track changes in DNA methylation during cardiac differentiation. Methods and Results: The promoter region of Cdk1 (Cyclin-dependent kinase 1) or Sox2 (SRY-Box Transcription Factor 2) gene was cloned upstream of the small nuclear ribonucleoprotein polypeptide N (Snrpn) minimal promoter followed by a fluorescent reporter gene. Mouse induced pluripotent stem cells (iPSCs) carrying Sox2 GMR rapidly lost fluorescent reporter signal upon the induction of differentiation. Cdk1 GMR reporter signal was strong in undifferentiated iPSCs, and gradually decreased during directed cardiomyocyte (CM) differentiation. RT-qPCR and pyrosequencing demonstrated that the reduction of Sox2 and Cdk1 was regulated by hypermethylation of their CpG regions during cardiac differentiation. The present study demonstrated the dynamic DNA methylation along the course of cell cycle withdrawal during CM differentiation. Conclusion: The GMR reporter system can be a useful tool to monitor real-time epigenetic DNA modification at single-cell resolution.

An Unusual Presentation: High-Grade Serous Carcinoma of the Fallopian Tube Manifesting With Altered Mental Status Secondary to a Single Brain Metastasis-A Case Report and Review of the Literature.

Epithelial ovarian and fallopian cancers are aggressive lesions that rarely metastasize to the central nervous system. Brain metastases usually occur in the setting of known primary disease or widespread metastatic disease. However, in extremely rare cases, an isolated intracranial neoplasm may be the first presentation of fallopian cancer. To the best of our knowledge, only one such case has been reported previously. We present an illustrative case with multimodality imaging and histopathologic correlation of a fallopian tube carcinoma first presenting with altered mental status secondary to an isolated brain metastasis. A 64-year-old female with no pertinent medical history presented with altered mentation. Initial workup identified a 1.6 cm avidly enhancing, solitary brain lesion at the gray-white junction with associated vasogenic edema concerning for either central nervous system lymphoma or metastatic disease. Additional imaging identified a 7.5 × 3 cm left adnexal lesion, initially thought to be a hydrosalpinx with hemorrhage, but magnetic resonance imaging suggested gynecologic malignancy. No lesions elsewhere in the body were identified. Given the lack of locoregional or systemic disease, the intracranial and pelvic lesions were assumed to represent synchronous but distinct processes. The intracranial lesion was biopsied. Preliminary results were suggestive of lymphoma, but further analysis was consistent with high-grade serous carcinoma of müllerian origin. Positron emission tomography/computed tomography was performed to evaluate for other neoplastic lesions, only highlighting the intracranial and pelvic lesions. At this point, a diagnosis of metastatic fallopian cancer was made. The patient was taken for robot-assisted laparoscopy with surgical debulking of the pelvic neoplasm, pathology demonstrating high-grade serous carcinoma of the fallopian tube, matching that of the intracranial lesion. Even though rare, metastatic fallopian cancer should be considered in patients with isolated brain lesions and adnexal lesions, even in the absence of locoregional or systemic disease.

SNAPIG: a model to study nutrient digestion and absorption kinetics in growing pigs based on diet and ingredient properties.

Current feed formulation and evaluation practices rely on static values for the nutritional value of feed ingredients and assume additivity. Hereby, the complex interplay among nutrients in the diet and the highly dynamic digestive processes are ignored. Nutrient digestion kinetics and diet × animal interactions should be acknowledged to improve future predictions of the nutritional value of complex diets. Therefore, an in silico nutrient-based mechanistic digestion model for growing pigs was developed: "SNAPIG" (Simulating Nutrient digestion and Absorption kinetics in PIGs). Aiming to predict the rate and extent of nutrient absorption from diets varying in ingredient composition and physicochemical properties, the model represents digestion kinetics of ingested protein, starch, fat, and non-starch polysaccharides, through passage, hydrolysis, absorption, and endogenous secretions of nutrients along the stomach, proximal small intestine, distal small intestine, and caecum + colon. Input variables are nutrient intake and the physicochemical properties (i.e. solubility, and rate and extent of degradability). Data on the rate and extent of starch and protein hydrolysis of different ingredients per digestive segment were derived from in vitro assays. Passage of digesta from the stomach was modelled as a function of feed intake level, dietary nutrient solubility and diet viscosity. Model evaluation included testing against independent data from in vivo studies on nutrient appearance in (portal) blood of growing pigs. When simulating diets varying in physicochemical properties and nutrient source, SNAPIG can explain variation in glucose absorption kinetics (postprandial time of peak, TOP: 20-100 min observed vs 25-98 min predicted), and predict variation in the extent of ileal protein and fat digestion (root mean square prediction errors (RMSPE) = 12 and 16%, disturbance error = 12 and 86%, and concordance correlation coefficient = 0.34 and 0.27). For amino acid absorption, the observed variation in postprandial TOP (61 ± 11 min) was poorly predicted despite accurate mean predictions (58 ± 34 min). Recalibrating protein digestion and amino acid absorption kinetics require data on net-portal nutrient appearance, combined with observations on digestion kinetics, in pigs fed diets varying in ingredient composition. Currently, SNAPIG can be used to forecast the time and extent of nutrient digestion and absorption when simulating diets varying in ingredient and nutrient composition. It enhances our quantitative understanding of nutrient digestion kinetics and identifies knowledge gaps in this field of research. Already useful as research tool, SNAPIG can be coupled with a postabsorptive metabolism model to predict the effects of dietary and feeding-strategies on the pig's growth response.

Relationships of BRAF V600E Gene Mutation With Some Immunohistochemical Markers and Recurrence Rate in Patients With Thyroid Carcinoma.

Background: The B-type rafkinase (BRAF) V600E gene mutation plays an important role in the pathogenesis, diagnosis, and prognosis of thyroid carcinoma. This study was conducted to investigate the rate of the BRAF V600E mutation, the relationships between the BRAF V600E gene mutation and some immunohistochemical markers, and recurrence rate in patients with differentiated thyroid cancer. Method: The study was conducted by a descriptive and longitudinal follow-up method on 102 thyroid carcinoma patients at 103 Military Hospital, Hanoi, Vietnam. All patients were identified with the BRAF V600E gene mutation by real-time polymerase chain reaction. Results: The rate of BRAF V600E gene mutation in patients with thyroid cancer was 60.8%. Patients with BRAF V600E gene mutation had a significantly higher rate of positive cyclooxygenase 2 (COX-2) and Ki67 markers than those without the mutation (COX-2: odds ratio [OR] = 2.93; 95% confidence interval [CI] = 1.27-6.74, P = .011; Ki67: OR = 3.41; 95% CI = 1.31-8.88, P = .01). A statistically significant relationship was identified between the rate of BRAF V600E mutation and the rate of positive Hector Battifora mesothelial 1 (HBME-1) (B = -1.040; P = .037) and COX-2 (B = -1.123; P = .023) markers. The recurrence rate in patients with BRAF V600E gene mutation was significantly higher than that in those without the mutation (P = .007). The mean of the recurrence time of patients with BRAF V600E mutation was significantly lower than that in those without the mutation (P = .011). Conclusions: A high prevalence of BRAF V600E gene mutation was found in thyroid carcinoma patients. The rates of positive HBME-1, COX-2, and Ki67 markers were significantly correlated to BRAF V600E gene mutation. Patients with BRAF V600E gene mutation showed a significantly higher relapse rate and earlier relapse time than those without the mutation.

Animal board invited review: Quantification of resilience in farm animals.

Resilience, when defined as the capacity of an animal to respond to short-term environmental challenges and to return to the prechallenge status, is a dynamic and complex trait. Resilient animals can reinforce the capacity of the herd to cope with often fluctuating and unpredictable environmental conditions. The ability of modern technologies to simultaneously record multiple performance measures of individual animals over time is a huge step forward to evaluate the resilience of farm animals. However, resilience is not directly measurable and requires mathematical models with biologically meaningful parameters to obtain quantitative resilience indicators. Furthermore, interpretive models may also be needed to determine the periods of perturbation as perceived by the animal. These applications do not require explicit knowledge of the origin of the perturbations and are developed based on real-time information obtained in the data during and outside the perturbation period. The main objective of this paper was to review and illustrate with examples, different modelling approaches applied to this new generation of data (i.e., with high-frequency recording) to detect and quantify animal responses to perturbations. Case studies were developed to illustrate alternative approaches to real-time and post-treatment of data. In addition, perspectives on the use of hybrid models for better understanding and predicting animal resilience are presented. Quantification of resilience at the individual level makes possible the inclusion of this trait into future breeding programmes. This would allow improvement of the capacity of animals to adapt to a changing environment, and therefore potentially reduce the impact of disease and other environmental stressors on animal welfare. Moreover, such quantification allows the farmer to tailor the management strategy to help individual animals to cope with the perturbation, hence reducing the use of pharmaceuticals, and decreasing the level of pain of the animal.

Expansion of non-invasive prenatal screening to the screening of 10 types of chromosomal anomalies: a cost-effectiveness analysis.

OBJECTIVES: To determine the cost-effectiveness of the addition of chromosomal anomalies detectable by non-invasive prenatal screening (NIPS), in a prenatal screening programme targeting common aneuploidies. DESIGN, SETTING AND PARTICIPANTS: A simulation study was conducted to study the addition of chromosomal anomalies detectable by NIPS (sex chromosome aneuploidies, 22q11.2 deletion syndrome, large deletion/duplication >7 Mb and rare autosomal trisomies) to five basic strategies currently aiming the common trisomies: three strategies currently offered by the public healthcare systems in Canada, whose first-tier test is performed with biochemical markers, and two programmes whose first-tier test consists of NIPS-based methods. OUTCOME MEASURES: The total number of cases of chromosomal anomalies detected and the costs related to the consumption of medical services. RESULTS: The most effective and the most cost-effective option in almost all prenatal screening strategies is the option that includes all targeted additional conditions. In the strategies where NIPS is used as first-tier testing, the cost per additional case detected by adding all possible additional anomalies to a programme that currently targets only common trisomies is $C25 710 (95% CI $C25 489 to $C25 934) for massively parallel shotgun sequencing and $C57 711 (95% CI $C57 141 to $C58 292) for targeted massively parallel sequencing, respectively. The acceptability curves show that at a willingness-to-pay of $C50 000 per one additional case detected, the expansion of NIPS-based methods for the detection of all possible additional conditions has a 90% probability of being cost-effective. CONCLUSION: From an economic perspective, in strategies that use NIPS as a first-tier screening test, expanding the programmes to detect any considered chromosomal anomalies other than the three common trisomies would be cost-effective. However, the potential expansion of prenatal screening programmes also requires consideration of societal issues, including ethical ones.

Minimum information and guidelines for reporting a Multiplexed Assay of Variant Effect.

Multiplexed Assays of Variant Effect (MAVEs) have emerged as a powerful approach for interrogating thousands of genetic variants in a single experiment. The flexibility and widespread adoption of these techniques across diverse disciplines has led to a heterogeneous mix of data formats and descriptions, which complicates the downstream use of the resulting datasets. To address these issues and promote reproducibility and reuse of MAVE data, we define a set of minimum information standards for MAVE data and metadata and outline a controlled vocabulary aligned with established biomedical ontologies for describing these experimental designs.