Combining sentiment analysis and text mining with content analysis of farm vet interviews on mental wellbeing in livestock practice.

BACKGROUND: The aim of the How Farm Vets Cope project was to co-design, with farm veterinary surgeons, a set of web-based resources to help them and others deal with the different situations that they can face. As part of the wider project, participants were recruited for one-to-one semi-structured phone interviews. These interviews focused on elements of job satisfaction and how the participants coped during periods of poor mental wellbeing or with setbacks and failure. METHODS: Transcripts of these interviews were analysed using both quantitative methods of sentiment analysis and text mining, including term frequency/inverse document frequency and rapid automated keyword extraction, and qualitative content analysis. The twin aims of the analysis were identifying the important themes discussed by the participants and comparing the results of the two methods to see what differences, if any, arose. RESULTS: Analysis using the afinn and nrc sentiment lexicons identified emotional themes of anticipation and trust. Rapid automated keyword extraction highlighted issues around age of vets and support, whilst using term frequency/inverse document frequency allowed for individual themes, such as religion, not present across all responses, to be identified. Content analysis supported these findings, pinpointing examples of trust around relationships with farmers and more experienced vets, along with some examples of the difference good support networks can make, particularly to younger vets. FINDINGS: This work has confirmed previous results in identifying the themes of trust, communication and support to be integral to the experience of practicing farm veterinary surgeons. Younger or less experienced vets recognised themselves as benefiting from further support and signposting, leading to a discussion around the preparation of veterinary students for entry into a farm animal vet practice. The two different approaches taken showed very good agreement in their results. The quantitative approaches can be scaled to allow a larger number of interviews to be utilised in studies whilst still allowing the important qualitative results to be identified.

Corrigendum: Evaluations of the disease surveillance centre network in Scotland: what parts has it reached?

[This corrects the article DOI: 10.3389/fvets.2023.1099057.].

Evaluations of the Disease Surveillance Centre network in Scotland: What parts has it reached?

Regular evaluation is a prerequisite for systems that provide surveillance of animal populations. Scotland's Rural College Veterinary Services' Disease Surveillance Centre (DSC) network plays an integral part in surveillance to detect new and re-emerging threats within animal populations, predominantly livestock. In response to surveillance reviews and proposed changes to the network, an initial evaluation of diagnostic submissions data in 2010 to mid-2012 established a baseline "footprint," while highlighting challenges with the data. In this recent evaluation for the period 2013­2018, we developed a new denominator using a combination of agricultural census and movement data, to identify relevant holdings more accurately. Iterative discussions between those processing submissions data and those involved in collection at source took place to understand the intricacies of the data, establish the most appropriate dataset, and develop the processes required to optimise the data extraction and cleansing. The subsequent descriptive analysis identifies the number of diagnostic submissions, the number of unique holdings making submissions to the network and shows that both the surrounding geographic region of, and maximum distance to the closest DSC vary greatly between centres. Analysis of those submissions classed as farm animal post-mortems also highlights the effect of distance to the closest DSC. Whether specific differences between the time periods are due to changes in the behavior of the submitting holdings or the data extraction and cleaning processes was difficult to disentangle. However, with the improved techniques producing better data to work with, a new baseline footprint for the network has been created. This provides information that can help policy makers and surveillance providers make decisions about service provision and evaluate the impact of future changes. Additionally, the outputs of these analyses can provide feedback to those employed in the service, providing evidence of what they are achieving and why changes to data collection processes and ways of working are being made. In a different setting, other data will be available and different challenges may arise. However, the fundamental principles highlighted in these evaluations and the solutions developed should be of interest to any surveillance providers generating similar diagnostic data.

Repair of a Late Presentation Thoracic Aortic Aneurysm following Coarctation Repair.

We report the case of a 44-year-old gentleman who underwent coarctation repair at the age of 7 years. He was lost to follow-up and represented. Computed tomography scan demonstrated a 9.8-cm diameter aortic aneurysm involving the distal aortic arch and proximal descending aorta. Open surgery was performed to repair the aneurysm. The patient made an unremarkable recovery. He was followed up 12 weeks later, and significant improvement in preoperative symptoms was observed. This case demonstrates the importance of long-term follow-up.

Predictive semiology of psychogenic non-epileptic seizures in an epilepsy monitoring unit.

INTRODUCTION: The diagnosis of psychogenic nonepileptic seizures (PNES) is a common clinical dilemma. We sought to assess the diagnostic value of four ictal signs commonly used in differentiating PNES from epileptic seizures (ES). METHODS: We retrospectively reviewed consecutive adult video-electroencephalogram (VEM) studies conducted at a single tertiary epilepsy center between May 2009 and August 2016. Each event was assessed by a blinded rater for the presence of four signs: fluctuating course, head shaking, hip thrusting, and back arching. The final diagnosis of PNES or ES was established for each event based on clinical and VEM characteristics. All ES were pooled regardless of focal or generalized onset. We analyzed the odds ratio of each sign in PNES in comparison to ES with adjustment for repeated measures using logistic regression. Additionally, we calculated the sensitivity, specificity, predictive values, and likelihood ratios of each sign to diagnose PNES. RESULTS: A total of 742 events from 140 VEM studies were assessed. Fluctuating course (odds ratio (OR) 37.37, 95% confidence interval (CI) 13.56-102.96, P < 0.0001), head shaking (OR 2.95, 95% CI 1.26-6.79, P = 0.012), and hip thrusting (OR 4.28, 95% CI 1.21-15.18, P = 0.02) were each significantly predictive of PNES. Fluctuating course had the highest sensitivity (76.16%). Back arching (OR 1.06, 95% CI 0.35-3.20, P = 0.92) was not significantly associated with PNES. CONCLUSION: Fluctuating course, head shaking, and hip thrusting are semiological features significantly more common in PNES than ES. Fluctuating course is the most reliable sign. Back arching does not appear to differentiate PNES from ES.

Quantifying changes in the British cattle movement network.

The modelling of disease spread is crucial to the farming industry and policy makers. In some of these industries, excellent data exist on animal movements, along with the networks that these movements create, and allow researchers to model spread of disease (both epidemic and endemic). The Cattle Tracing System is an online recording system for cattle births, deaths and between-herd movements in the United Kingdom and is an excellent resource for any researchers interested in networks or modelling infectious disease spread through the UK cattle system. Data exist that cover many years, and it can be useful to know how much change is occurring in a network, to help judge the merit of using historical data within a modelling context. This article uses the data to construct weighted directed monthly movement networks for two distinct periods of time, 2004-2006 and 2015-2017, to quantify by how much the underlying structure of the network has changed. Substantial changes in network structure may influence policy-makers directly or may influence models built upon the network data, and these in turn could impact policy-makers and their assessment of risk. We examined 13 network metrics, ranging from general descriptive metrics such as total number of nodes with movements and total movements, through to metrics to describe the network (e.g., Giant weakly and strongly connected components) and metrics calculated per node (betweenness, degree and strength). Mixed effect models show that there is a statistically significant effect of the period (2004-2006 vs 2015-2017) in the values of nine of the 13 network metrics. For example median total degree decreased by 19%. In addition to examining networks for two time periods, two updates of the data were examined to determine by how much the movement data stored for 2004-2006 had been cleansed between updates. Examination of these updates shows that there are small decreases in problem movements (such as animals leaving slaughterhouses) and therefore evidence of historical data being improved between updates. In combination with the significant effect of period on many of the network metrics, the modification of data between updates provides further evidence that the most recent available data should be used for network modelling. This will ensure that the most representative descriptions of the network are available to provide accurate modelling results to best inform policy makers.

Topochemical Synthesis of Single-Crystalline Hydrogen-Bonded Cross-Linked Organic Frameworks and Their Guest-Induced Elastic Expansion.

Covalently linked single-crystalline porous organic materials are highly desired for structure-property analysis; however, periodically polymerizing organic entities into high dimensional networks is challenging. Here, we report a series of topologically divergent single-crystalline hydrogen-bonded cross-linked organic frameworks (HCOFs) with visible guest-induced elastic expansions, which mutually integrate high structural order and high flexibility into one framework. These HCOFs are synthesized by photo-cross-linking molecular crystals with alkyldithiols of different chain lengths. Their detailed structural information was revealed by single-crystal X-ray analysis and experimental investigations of HCOFs and their corresponding single-crystalline analogues. Upon guest adsorption, HCOF-2 crystals composed of a 3D self-entangled polymer network undergo anisotropic expansion to more than twice their original size, while the 2D-bilayer HCOF-3 crystals exhibit visible, layered sorption bands and form delaminated sheets along the plane of its 2D layers. The dynamic expansion of HCOF networks creates guest-induced porosity with over 473% greater volume than their permanent voids, as calculated from their record-breaking aqueous iodine adsorption capacities. Temperature-gated DMSO sorption investigations illustrated that the flexible nature of cross-linkers in HCOFs provides positive entropy from the coexistence of multiple conformations to allow for elastic expansion and contraction of the frameworks.

Advanced Polymer Designs for Direct-Ink-Write 3D Printing.

The rapid development of additive manufacturing techniques, also known as three-dimensional (3D) printing, is driving innovations in polymer chemistry, materials science, and engineering. Among current 3D printing techniques, direct ink writing (DIW) employs viscoelastic materials as inks, which are capable of constructing sophisticated 3D architectures at ambient conditions. In this perspective, polymer designs that meet the rheological requirements for direct ink writing are outlined and successful examples are summarized, which include the development of polymer micelles, co-assembled hydrogels, supramolecularly cross-linked systems, polymer liquids with microcrystalline domains, and hydrogels with dynamic covalent cross-links. Furthermore, advanced polymer designs that reinforce the mechanical properties of these 3D printing materials, as well as the integration of functional moieties to these materials are discussed to inspire new polymer designs for direct ink writing and broadly 3D printing.

Putting Cocrystal Stoichiometry to Work: A Reactive Hydrogen-Bonded "Superassembly" Enables Nanoscale Enlargement of a Metal-Organic Rhomboid via a Solid-State Photocycloaddition.

Enlargement of a self-assembled metal-organic rhomboid is achieved via the organic solid state. The solid-state synthesis of an elongated organic ligand was achieved by a template directed [2 + 2] photodimerization in a cocrystal. Initial cocrystals obtained of resorcinol template and reactant alkene afforded a 1:2 cocrystal with the alkene in a stacked yet photostable geometry. Cocrystallization performed in the presence of excess template resulted in a 3:2 cocrystal composed of novel discrete 10-component hydrogen-bonded "superassemblies" wherein the alkenes undergo a head-to-head [2 + 2] photodimerization. Isolation and reaction of elongated photoproduct with Cu(II) ions afforded a metal-organic rhomboid of nanoscale dimensions that hosts small molecules in the solid state as guests.

Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies.

SOX8 is an HMG-box transcription factor closely related to SRY and SOX9. Deletion of the gene encoding Sox8 in mice causes reproductive dysfunction but the role of SOX8 in humans is unknown. Here, we show that SOX8 is expressed in the somatic cells of the early developing gonad in the human and influences human sex determination. We identified two individuals with 46, XY disorders/differences in sex development (DSD) and chromosomal rearrangements encompassing the SOX8 locus and a third individual with 46, XY DSD and a missense mutation in the HMG-box of SOX8. In vitro functional assays indicate that this mutation alters the biological activity of the protein. As an emerging body of evidence suggests that DSDs and infertility can have common etiologies, we also analysed SOX8 in a cohort of infertile men (n = 274) and two independent cohorts of women with primary ovarian insufficiency (POI; n = 153 and n = 104). SOX8 mutations were found at increased frequency in oligozoospermic men (3.5%; P < 0.05) and POI (5.06%; P = 4.5 × 10-5) as compared with fertile/normospermic control populations (0.74%). The mutant proteins identified altered SOX8 biological activity as compared with the wild-type protein. These data demonstrate that SOX8 plays an important role in human reproduction and SOX8 mutations contribute to a spectrum of phenotypes including 46, XY DSD, male infertility and 46, XX POI.

Kisspeptin Is a Novel Regulator of Human Fetal Adrenocortical Development and Function: A Finding With Important Implications for the Human Fetoplacental Unit.

Context: The human fetal adrenal (HFA) is an integral component of the fetoplacental unit and important for the maintenance of pregnancy. Low kisspeptin levels during pregnancy are associated with miscarriage, and kisspeptin and its receptor are expressed in the HFA. However, the role of kisspeptin in fetal adrenal function remains unknown. Objective: To determine the role of kisspeptin in the developing HFA. Design: Experiments using H295R and primary HFA cells as in vitro models of the fetal adrenal. Association of plasma kisspeptin levels with HFA size in a longitudinal clinical study. Setting: Academic research center and tertiary fetal medicine unit. Participants: Thirty-three healthy pregnant women were recruited at their 12-week routine antenatal ultrasound scan. Main Outcome Measures: The spatiotemporal expression of Kiss1R in the HFA. The production of dehydroepiandrosterone sulfate (DHEAS) from HFA cells after kisspeptin treatment, alone or in combination with adrenocorticotropic hormone or corticotropin-releasing hormone. Fetal adrenal volume (FAV) and kisspeptin levels at four antenatal visits (∼20, 28, 34, and 38 weeks' gestation). Results: Expression of Kiss1R was present in the HFA from 8 weeks after conception to term and was shown in the inner fetal zone. Kisspeptin significantly increased DHEAS production in H295R and second-trimester HFA cells. Serial measurements of kisspeptin confirmed a correlation with FAV growth in the second trimester, independent of sex or estimated fetal weight. Conclusions: Kisspeptin plays a key role in the regulation of the HFA and thus the fetoplacental unit, particularly in the second trimester of pregnancy.

A genomic atlas of human adrenal and gonad development.

BACKGROUND: In humans, the adrenal glands and gonads undergo distinct biological events between 6-10 weeks post conception (wpc), such as testis determination, the onset of steroidogenesis and primordial germ cell development. However, relatively little is currently known about the genetic mechanisms underlying these processes. We therefore aimed to generate a detailed genomic atlas of adrenal and gonad development across these critical stages of human embryonic and fetal development. METHODS: RNA was extracted from 53 tissue samples between 6-10 wpc (adrenal, testis, ovary and control). Affymetrix array analysis was performed and differential gene expression was analysed using Bioconductor. A mathematical model was constructed to investigate time-series changes across the dataset. Pathway analysis was performed using ClueGo and cellular localisation of novel factors confirmed using immunohistochemistry. RESULTS: Using this approach, we have identified novel components of adrenal development (e.g. ASB4, NPR3) and confirmed the role of SRY as the main human testis-determining gene. By mathematical modelling time-series data we have found new genes up-regulated with SOX9 in the testis (e.g. CITED1), which may represent components of the testis development pathway. We have shown that testicular steroidogenesis has a distinct onset at around 8 wpc and identified potential novel components in adrenal and testicular steroidogenesis (e.g. MGARP, FOXO4, MAP3K15, GRAMD1B, RMND2), as well as testis biomarkers (e.g. SCUBE1). We have also shown that the developing human ovary expresses distinct subsets of genes (e.g. OR10G9, OR4D5), but enrichment for established biological pathways is limited. CONCLUSION: This genomic atlas is revealing important novel aspects of human development and new candidate genes for adrenal and reproductive disorders.

Quantitative and regiocontrolled cross-photocycloaddition of the anticancer drug 5-fluorouracil achieved in a cocrystal.

We describe a [2+2] cross-photocycloaddition of the anticancer drug 5-fluorouracil in the solid state that proceeds regioselectively and in quantitative yield. The photocycloaddition occurs in a cocrystal with trans-2,2'-bis(pyridyl)ethylene.

DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human disease.

DAX-1 (NR0B1) and SF-1 (NR5A1) are two nuclear receptor transcription factors that play a key role in human adrenal and reproductive development. Loss of DAX-1 function is classically associated with X-linked adrenal hypoplasia congenita. This condition typically affects boys and presents as primary adrenal insufficiency in early infancy or childhood, hypogonadotropic hypogonadism at puberty and impaired spermatogenesis. Late onset forms of this condition and variant phenotypes are increasingly recognized. In contrast, disruption of SF-1 only rarely causes adrenal insufficiency, usually in combination with testicular dysgenesis. Variants in SF-1/NR5A1 more commonly cause a spectrum of reproductive phenotypes ranging from 46,XY DSD (partial testicular dysgenesis or reduced androgen production) and hypospadias to male factor infertility or primary ovarian insufficiency. Making a specific diagnosis of DAX-1 or SF-1 associated conditions is important for long-term monitoring of endocrine and reproductive function, appropriate genetic counselling for family members, and for providing appropriate informed support for young people.

The role and interaction of imprinted genes in human fetal growth.

Identifying the genetic input for fetal growth will help to understand common, serious complications of pregnancy such as fetal growth restriction. Genomic imprinting is an epigenetic process that silences one parental allele, resulting in monoallelic expression. Imprinted genes are important in mammalian fetal growth and development. Evidence has emerged showing that genes that are paternally expressed promote fetal growth, whereas maternally expressed genes suppress growth. We have assessed whether the expression levels of key imprinted genes correlate with fetal growth parameters during pregnancy, either early in gestation, using chorionic villus samples (CVS), or in term placenta. We have found that the expression of paternally expressing insulin-like growth factor 2 (IGF2), its receptor IGF2R, and the IGF2/IGF1R ratio in CVS tissues significantly correlate with crown-rump length and birthweight, whereas term placenta expression shows no correlation. For the maternally expressing pleckstrin homology-like domain family A, member 2 (PHLDA2), there is no correlation early in pregnancy in CVS but a highly significant negative relationship in term placenta. Analysis of the control of imprinted expression of PHLDA2 gave rise to a maternally and compounded grand-maternally controlled genetic effect with a birthweight increase of 93/155 g, respectively, when one copy of the PHLDA2 promoter variant is inherited. Expression of the growth factor receptor-bound protein 10 (GRB10) in term placenta is significantly negatively correlated with head circumference. Analysis of the paternally expressing delta-like 1 homologue (DLK1) shows that the paternal transmission of type 1 diabetes protective G allele of rs941576 single nucleotide polymorphism (SNP) results in significantly reduced birth weight (-132 g). In conclusion, we have found that the expression of key imprinted genes show a strong correlation with fetal growth and that for both genetic and genomics data analyses, it is important not to overlook parent-of-origin effects.

Mutations in SNX14 cause a distinctive autosomal-recessive cerebellar ataxia and intellectual disability syndrome.

Intellectual disability and cerebellar atrophy occur together in a large number of genetic conditions and are frequently associated with microcephaly and/or epilepsy. Here we report the identification of causal mutations in Sorting Nexin 14 (SNX14) found in seven affected individuals from three unrelated consanguineous families who presented with recessively inherited moderate-severe intellectual disability, cerebellar ataxia, early-onset cerebellar atrophy, sensorineural hearing loss, and the distinctive association of progressively coarsening facial features, relative macrocephaly, and the absence of seizures. We used homozygosity mapping and whole-exome sequencing to identify a homozygous nonsense mutation and an in-frame multiexon deletion in two families. A homozygous splice site mutation was identified by Sanger sequencing of SNX14 in a third family, selected purely by phenotypic similarity. This discovery confirms that these characteristic features represent a distinct and recognizable syndrome. SNX14 encodes a cellular protein containing Phox (PX) and regulator of G protein signaling (RGS) domains. Weighted gene coexpression network analysis predicts that SNX14 is highly coexpressed with genes involved in cellular protein metabolism and vesicle-mediated transport. All three mutations either directly affected the PX domain or diminished SNX14 levels, implicating a loss of normal cellular function. This manifested as increased cytoplasmic vacuolation as observed in cultured fibroblasts. Our findings indicate an essential role for SNX14 in neural development and function, particularly in development and maturation of the cerebellum.

Two act as one: unexpected dimers of catechol direct a solid-state [2+2] photodimerization in a six-component hydrogen-bonded assembly.

We describe hydrogen-bonded dimers of catechol that act collectively as a single template to direct an intermolecular [2+2] photocycloaddition in the solid state. The directed reactivity involves discrete, six-component hydrogen-bonded assemblies and a photoreaction that occurs stereoselectively and in quantitative yield.

Maternal inheritance of a promoter variant in the imprinted PHLDA2 gene significantly increases birth weight.

Birth weight is an important indicator of both perinatal and adult health, but little is known about the genetic factors contributing to its variability. Intrauterine growth restriction is a leading cause of perinatal morbidity and mortality and is also associated with adult disease. A significant correlation has been reported between lower birth weight and increased expression of the maternal PHLDA2 allele in term placenta (the normal imprinting pattern was maintained). However, a mechanism that explains the transcriptional regulation of PHLDA2 on in utero growth has yet to be described. In this study, we sequenced the PHLDA2 promoter region in 263 fetal DNA samples to identify polymorphic variants. We used a luciferase reporter assay to identify in the PHLDA2 promoter a 15 bp repeat sequence (RS1) variant that significantly reduces PHLDA2-promoter efficiency. RS1 genotyping was then performed in three independent white European normal birth cohorts. Meta-analysis of all three (total n = 9,433) showed that maternal inheritance of RS1 resulted in a significant 93 g increase in birth weight (p = 0.01; 95% confidence interval [CI] = 22-163). Moreover, when the mother was homozygous for RS1, the influence on birth weight was 155 g (p = 0.04; 95% CI = 9-300), which is a similar magnitude to the reduction in birth weight caused by maternal smoking.