Early silique-shedding wild radish (Raphanus raphanistrum L.) phenotypes persist in a long-term harvest weed seed control managed field in Western Australia.

BACKGROUND: This study introduces a wild radish population collected from Yelbeni in the Western Australian grainbelt that evolved an early silique abscission (shedding) trait to persist despite long-term harvest weed seed control (HWSC) use. In 2017, field-collected seed (known herein as Yelbeni) was compared to surrounding ruderal and field-collected populations in a fully randomized common garden study. RESULTS: The Yelbeni population exhibited a higher rate of silique abscission when compared to the ruderal populations collected from the site before wheat (Triticum aestivum L.) harvest (assessed at soft dough stage, Zadoks 83). A similar common garden study was conducted in the subsequent season (2018) using progeny reproduced on a single site without stress. The HWSC-selected progeny (Yelbeni P) shed 1048 (±288) siliques before wheat maturity at the soft dough stage (Zadoks 83) compared to 25 (±7) siliques from the pooled control populations. The Yelbeni P population only flowered 6 days earlier (FT50 as determined by log-logistic analysis) than pooled control populations, which is unlikely to fully account for the increased rate of silique abscission. The Yelbeni P population also located its lowest siliques below the lowest height for harvest interception (10 cm), which is likely to increase HWSC evasion. The mechanism inducing early silique-shedding is yet to be determined; however, wild radish is known for its significant genetic variability and has demonstrated its capacity to adapt to environmental and management stresses. CONCLUSION: This study demonstrates that the repeated use of HWSC can lead to the selection of HWSC-avoidance traits including early silique-shedding before harvest and/or locating siliques below the harvest cutting height for interception. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

The genome sequence of the Figwort Cheilosia, Cheilosia variabilis (Panzer, 1798).

We present a genome assembly from an individual male Cheilosia variabilis (the Figwort Cheilosia; Arthropoda; Insecta; Diptera; Syrphidae). The genome sequence is 414.7 megabases in span. Most of the assembly is scaffolded into 7 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 16.77 kilobases in length.

The genome sequence of the thick-headed fly, Myopa tessellatipennis (Motschulsky, 1859).

We present a genome assembly from an individual female Myopa tessellatipennis (Arthropoda; Insecta; Diptera; Conopidae). The genome sequence is 249.3 megabases in span. Most of the assembly is scaffolded into four chromosomal pseudomolecules, including the assembled X sex chromosome. The mitochondrial genome has also been assembled and is 18.3 kilobases in length.

The genome sequence of the flutter-wing fly, Palloptera scutellata (Macquart, 1835).

We present a genome assembly from an individual female Palloptera scutellata (the flutter-wing fly; Arthropoda; Insecta; Diptera; Pallopteridae). The genome sequence is 415.6 megabases in span. Most of the assembly is scaffolded into 5 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 15.93 kilobases in length.

Enhancing the utility of antroduodenal manometry in pediatric intestinal pseudo-obstruction.

BACKGROUND: Antroduodenal manometry (ADM) and histopathology are currently employed to aid the diagnosis of pediatric intestinal pseudo-obstruction (PIPO). Limited data are available on the reliability of ADM analysis and its correlation with histopathology. We aimed to develop a protocol for enhanced analysis of ADM contractile patterns, including a scoring system, and explore whether this provided better correlation with histopathology. METHODS: Children referred with suspected PIPO between April 2012-December 2019 who underwent both ADM and full-thickness biopsies were included. ADM tracings were analyzed using both standard (conventional ADM) and novel (enhanced ADM) motility parameters. A novel ADM score (GLASS score) was generated based on the enhanced ADM analysis. Conventional and enhanced ADM analyses were then correlated with histopathology. RESULTS: Forty patients were included. Using conventional clinical criteria, 29 of these were diagnosed with PIPO and the other 11 with non-PIPO diagnoses. Twenty-three of the PIPO patients had abnormal histopathology: 6 myopathy, 4 neuropathy, 3 neuro-myopathy, and 10 non-specific changes. No agreement in diagnosis was found between conventional ADM analysis and histopathology (Ï° = 0.068; p = 0.197), whereas the latter significantly correlated with enhanced ADM analysis (Ï° = 0.191; p = 0.003). The enhanced ADM score was significantly higher in PIPO versus non-PIPO (16.0 vs. 8.0; p < 0.001). CONCLUSIONS: As opposed to conventional analysis protocols, the newly developed enhanced ADM analysis and associated score is not only able to discriminate between PIPO and non-PIPO patients, but also between distinct histopathological pathologies. Further studies are required to assess the utility of enhanced ADM analysis in larger populations.

Mosaic PRKACA duplication causing a novel and distinct phenotype of early-onset Cushing's syndrome and acral cutaneous mucinosis.

SIGNIFICANCE STATEMENT: We describe a mosaic PRKACA duplication in a young infant who presented with a Carney-like complex: bilateral non-pigmented micronodular adrenal hyperplasia, severe early-onset Cushing's syndrome, and distinct acral soft tissue overgrowth due to cutaneous mucinosis. This represents a novel manifestation of PRKACA disruption and broadens the extra-adrenal phenotype of PRKACA-associated Cushing's syndrome. Our data suggest that Cushing's syndrome phenotypes arising from somatic and germline PRKACA abnormalities can exist on a spectrum. We emphasise the value of ascertaining a genetic diagnosis for PRKACA-mediated adrenal and extra-adrenal disease to guide individualised and targeted care.

Enacting a depoliticised alterity: law and traditional medicine at the World Health Organization.

This paper interrogates the depoliticising effects of a seemingly neutral regulatory drive at the heart of the World Health Organization (WHO)'s promotion of traditional medicine. Emerging at WHO in the late 1960s against a political backdrop of decolonisation and pan-Africanism, traditional medicine has continued to be promoted in subsequent decades, culminating in the latest global Traditional Medicine Strategy (2014 to 2023). Yet WHO's promotion and acceptance of traditional medicine have also become increasingly conditional upon its standardisation and regulation - something that appears fundamentally at odds with traditional medicine's heterogeneity. Drawing on insights from critical law and science and technology studies, we suggest that such a process at WHO has done more than simply disqualify the toxic and the dangerous. Rather, it has implicitly and explicitly marginalised and excluded those aspects of traditional medicine that deviate from scientific, biomedical ways of seeing, knowing and organising.

Micro-CT Imaging of Pediatric Thyroglossal Duct Cysts: A Prospective Case Series.

Objectives: To determine the feasibility of micro-CT as a high-resolution 3D imaging tool for thyroglossal duct cysts and to evaluate its role augmenting traditional histopathological examination of resected specimens. Methods: A single centre, prospective case series of consecutive children undergoing excision of a thyroglossal duct cyst was performed at a quaternary paediatric referral hospital in the United Kingdom. Consecutive children listed for excision of a thyroglossal duct cyst whose parents agreed to participate were included and there were no exclusion criteria. Results: Surgically excised thyroglossal duct cyst or remnant specimens from five patients (two males, three females) were examined using micro-CT alongside traditional histopathological examination. In all cases, micro-CT imaging was able to demonstrate 3D imaging datasets of the specimens successfully and direct radio-pathological comparisons were made (Figures 1-5, Supplementary Video 1). Conclusions: The study has shown the feasibility and utility of post-operative micro-CT imaging of thyroglossal duct cysts specimens as a visual aid to traditional histopathological examination. It better informs the pathological specimen sectioning using multi-planar reconstruction and volume rendering tools without tissue destruction. In the complex, often arborised relationship between a thyroglossal duct cyst and the hyoid, micro-CT provides valuable image plane orientation and indicates proximity of the duct to the surgical margins. This is the first case series to explore the use of micro-CT imaging for pediatric thyroglossal duct specimens and it informs future work investigating the generalizability of micro-CT imaging methods for other lesions, particularly those from the head and neck region where precisely defining margins of excision may be challenging.

Legalities of Healing: Handling Alterities at the Edge of Medicine in France, 1980s-2010s.

The practice of healing by anyone other than qualified doctors or pharmacists has been allegedly illegal in France since the nineteenth century. In this judicial order, the state delegated the power to oversee the boundaries of medicine to doctors and pharmacists, allowing them, with support from criminal courts, to determine which therapeutic techniques should remain their exclusive right. In practice, this apparently neat legal system was never clear-cut; therapists without medical qualifications continued to infringe upon spaces that doctors and pharmacists saw as their preserve, often carving out zones of juridical tolerance. In the 1980s and 1990s, negotiations over the legality or illegality of different kinds of healing intensified. Alternative therapies, such as acupuncture and herbalism, had gained in popularity and their practitioners were keen to negotiate a legal position that would make their work licit. While some succeeded, others got entangled in a new governmental framework that characterized alternative medicines as gateways to "sects." This article examines these developments and explains how new juridical techniques to govern certaintherapies arose in the 1990s. These operated through decentralized surveillance systems that enrolled new actors. These included agencies dedicated to monitoring sects; associations of victims; and individuals such as users, their families, or health professionals. Together, they aimed to "prevent" deviant behavior, thereby fostering what is today one of the most peculiar features of the way the French state regulates alternative healing, which it considers potentially "cult-like."

Alpha-protein kinase 3 (ALPK3) truncating variants are a cause of autosomal dominant hypertrophic cardiomyopathy.

AIMS: The aim of this study was to determine the frequency of heterozygous truncating ALPK3 variants (ALPK3tv) in patients with hypertrophic cardiomyopathy (HCM) and confirm their pathogenicity using burden testing in independent cohorts and family co-segregation studies. METHODS AND RESULTS: In a discovery cohort of 770 index patients with HCM, 12 (1.56%) were heterozygous for ALPK3tv [odds ratio(OR) 16.11, 95% confidence interval (CI) 7.94-30.02, P = 8.05e-11] compared to the Genome Aggregation Database (gnomAD) population. In a validation cohort of 2047 HCM probands, 32 (1.56%) carried heterozygous ALPK3tv (OR 16.17, 95% CI 10.31-24.87, P < 2.2e-16, compared to gnomAD). Combined logarithm of odds score in seven families with ALPK3tv was 2.99. In comparison with a cohort of genotyped patients with HCM (n = 1679) with and without pathogenic sarcomere gene variants (SP+ and SP-), ALPK3tv carriers had a higher prevalence of apical/concentric patterns of hypertrophy (60%, P < 0.001) and of a short PR interval (10%, P = 0.009). Age at diagnosis and maximum left ventricular wall thickness were similar to SP- and left ventricular systolic impairment (6%) and non-sustained ventricular tachycardia (31%) at baseline similar to SP+. After 5.3 ± 5.7 years, 4 (9%) patients with ALPK3tv died of heart failure or had cardiac transplantation (log-rank P = 0.012 vs. SP- and P = 0.425 vs. SP+). Imaging and histopathology showed extensive myocardial fibrosis and myocyte vacuolation. CONCLUSIONS: Heterozygous ALPK3tv are pathogenic and segregate with a characteristic HCM phenotype.

Assessing the Capability and Potential of LiDAR for Weed Detection.

Conventional methods of uniformly spraying fields to combat weeds, requires large herbicide inputs at significant cost with impacts on the environment. More focused weed control methods such as site-specific weed management (SSWM) have become popular but require methods to identify weed locations. Advances in technology allows the potential for automated methods such as drone, but also ground-based sensors for detecting and mapping weeds. In this study, the capability of Light Detection and Ranging (LiDAR) sensors were assessed to detect and locate weeds. For this purpose, two trials were performed using artificial targets (representing weeds) at different heights and diameter to understand the detection limits of a LiDAR. The results showed the detectability of the target at different scanning distances from the LiDAR was directly influenced by the size of the target and its orientation toward the LiDAR. A third trial was performed in a wheat plot where the LiDAR was used to scan different weed species at various heights above the crop canopy, to verify the capacity of the stationary LiDAR to detect weeds in a field situation. The results showed that 100% of weeds in the wheat plot were detected by the LiDAR, based on their height differences with the crop canopy.

Preclinical Optimization and Safety Studies of a New Lentiviral Gene Therapy for p47phox-Deficient Chronic Granulomatous Disease.

Chronic granulomatous disease (CGD) is an inherited blood disorder of phagocytic cells that renders patients susceptible to infections and inflammation. A recent clinical trial of lentiviral gene therapy for the most frequent form of CGD, X-linked, has demonstrated stable correction over time, with no adverse events related to the gene therapy procedure. We have recently developed a parallel lentiviral vector for p47phox-deficient CGD (p47phoxCGD), the second most common form of this disease. Using this vector, we have observed biochemical correction of CGD in a mouse model of the disease. In preparation for clinical trial approval, we have performed standardized preclinical studies following Good Laboratory Practice (GLP) principles, to assess the safety of the gene therapy procedure. We report no evidence of adverse events, including mutagenesis and tumorigenesis, in human hematopoietic stem cells transduced with the lentiviral vector. Biodistribution studies of transduced human CD34+ cells indicate that the homing properties or engraftment ability of the stem cells is not negatively affected. CD34+ cells derived from a p47phoxCGD patient were subjected to an optimized transduction protocol and transplanted into immunocompromised mice. After the procedure, patient-derived neutrophils resumed their function, suggesting that gene correction was successful. These studies pave the way to a first-in-man clinical trial of lentiviral gene therapy for the treatment of p47phoxCGD.

Identification of the first glyphosate-resistant capeweed (Arctotheca calendula) population.

BACKGROUND: Glyphosate is routinely used in Australia to control the Arctotheca species Arctotheca calendula (L.) Levyns (referred hereinafter as capeweed). This study identifies the first global case of field-evolved glyphosate-resistant capeweed, collected from the grainbelt of Western Australia. RESULTS: In 2020, a capeweed biotype that was collected from Borden in the southern Western Australian grainbelt was confirmed to be glyphosate-resistant (referred hereinafter as Spence population). When compared to the pooled mortality of six field-collected, glyphosate susceptible capeweed populations (S1, S2, S3, S4, S5 and S6), the Spence population was found > 11-fold more resistant to glyphosate than the pooled results of the susceptible populations (S1-S6) at the lethal dose of 50% (LD50 ) level. The growth of the Spence population was also less affected, requiring > 13-fold more glyphosate to reduce growth than the pooled susceptible populations at the growth reduction of 50% (GR50 ) level. Sequencing of the plastidic 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene indicated no known single gene mutation imparting glyphosate resistance. This study, however, did not investigate any other known mechanisms that impart glyphosate resistance. When screened at the field-applied rate, this Spence population was also found to survive an inhibitor of acetolactate synthase (ALS) (metosulam) and an inhibitor of phytoene desaturase (diflufenican). CONCLUSIONS: This is the first confirmation of glyphosate resistance evolution in a capeweed population globally. With capeweed resistance already confirmed to photosystem-I inhibiting herbicides (paraquat and diquat), this study emphasizes the importance of using integrated measures that do not depend only on the use of non-selective herbicides for controlling herbicide resistance-prone capeweed populations. © 2021 Society of Chemical Industry.

The Novel Desmin Variant p.Leu115Ile Is Associated With a Unique Form of Biventricular Arrhythmogenic Cardiomyopathy.

BACKGROUND: Arrhythmogenic cardiomyopathy (AC) is a heritable myocardial disorder and a major cause of sudden cardiac death. It is typically caused by mutations in desmosomal genes. Desmin gene (DES) variants have been previously reported in AC but with insufficient evidence to support their pathogenicity. METHODS: We aimed to assess a large AC patient cohort for DES mutations and describe a unique phenotype associated with a recurring variant in three families. A cohort of 138 probands with a diagnosis of AC and no identifiable desmosomal gene mutations were prospectively screened by whole-exome sequencing. RESULTS: A single DES variant (p.Leu115Ile, c.343C>A) was identified in 3 index patients (2%). We assessed the clinical phenotypes within their families and confirmed cosegregation. One carrier required heart transplantation, 2 died suddenly, and 1 died of noncardiac causes. All cases had right- and left-ventricular (LV) involvement. LV late gadolinium enhancement was present in all, and circumferential subepicardial distribution was confirmed on histology. A significant burden of ventricular arrhythmias was noted. Desmin aggregates were not observed macroscopically, but analysis of the desmin filament formation in transfected cardiomyocytes derived from induced pluripotent stem cells, and SW13 cells revealed cytoplasmic aggregation of mutant desmin. Atomic force microscopy revealed that the mutant form accumulates into short protofilaments and small fibrous aggregates. CONCLUSIONS: DES p.Leu115Ile leads to disruption of the desmin filament network and causes a malignant biventricular form of AC, characterized by LV dysfunction and a circumferential subepicardial distribution of myocardial fibrosis.

Postmortem microfocus computed tomography for noninvasive autopsies: experience in >250 human fetuses.

BACKGROUND: Noninvasive imaging autopsy alternatives for fetuses weighing <500 grams are limited. Microfocus computed tomography has been reported as a viable option in small case series with the potential to avoid an invasive autopsy. Implementation of postmortem microfocus computed tomography in a large cohort as part of routine clinical service has yet been unreported, and realistic "autopsy prevention rates" are unknown. OBJECTIVE: This study aimed to describe the range of abnormalities detectable on fetal microfocus computed tomography in a clinical setting and additional findings identified on the antenatal ultrasound and to estimate the invasive autopsy avoidance rate (ie, cases in which imaging was sufficient to deem autopsy unnecessary). STUDY DESIGN: A prospective observational case series of all fetuses referred for microfocus computed tomography imaging at a single institution was conducted for 3 years (2016-2019). Imaging was reported by 2 pediatric radiologists before autopsy, with "decision to proceed" based on the specialist perinatal pathologists' judgment and parental consent. Agreement rates between microfocus computed tomography and antenatal ultrasound were evaluated, and where feasible, diagnostic accuracy for microfocus computed tomography was calculated using autopsy as a reference standard. RESULTS: A total of 268 fetuses were included (2-350 grams body weight; 11-24 weeks' gestation), with cause for demise in 122 of 268 (45.5%). Of the 122 fetuses, 64 (52.5%) exhibited fetal anomalies. Although 221 of 268 (82.5%) fetuses had consent for invasive autopsy, only 29 of the 221 (13.1%) underwent this procedure, which implied an autopsy avoidance rate of 192 of 221 (86.9%). Complete agreement was present for all brain, thoracic, and abdominal pathologies, whereas sensitivity and specificity for cardiac anomalies were 66.7% and 91.7%, respectively. Microfocus computed tomography and antenatal ultrasound agreement was found in 219 of 266 cases (81.9%), with partial agreement in 21 of 266 (7.9%) and disagreement in 26 of 266 (10.5%), mostly because of additional cardiac, soft tissue, or genitourinary findings by microfocus computed tomography, which were not seen on the ultrasound. CONCLUSION: Fetal microfocus computed tomography imaging is a viable and useful tool for imaging early gestational fetuses and can avoid the need for invasive autopsy. Confirmation of antenatal diagnoses is achieved in most cases, and additional anomalies may also be detected.

Cardiac phenotype in ATP1A3-related syndromes: A multicenter cohort study.

OBJECTIVE: To define the risks and consequences of cardiac abnormalities in ATP1A3-related syndromes. METHODS: Patients meeting clinical diagnostic criteria for rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) with ATP1A3 genetic analysis and at least 1 cardiac assessment were included. We evaluated the cardiac phenotype in an Atp1a3 knock-in mouse (Mashl+/-) to determine the sequence of events in seizure-related cardiac death. RESULTS: Ninety-eight patients with AHC, 9 with RDP, and 3 with CAPOS (63 female, mean age 17 years) were included. Resting ECG abnormalities were found in 52 of 87 (60%) with AHC, 2 of 3 (67%) with CAPOS, and 6 of 9 (67%) with RDP. Serial ECGs showed dynamic changes in 10 of 18 patients with AHC. The first Holter ECG was abnormal in 24 of 65 (37%) cases with AHC and RDP with either repolarization or conduction abnormalities. Echocardiography was normal. Cardiac intervention was required in 3 of 98 (≈3%) patients with AHC. In the mouse model, resting ECGs showed intracardiac conduction delay; during induced seizures, heart block or complete sinus arrest led to death. CONCLUSIONS: We found increased prevalence of ECG dynamic abnormalities in all ATP1A3-related syndromes, with a risk of life-threatening cardiac rhythm abnormalities equivalent to that in established cardiac channelopathies (≈3%). Sudden cardiac death due to conduction abnormality emerged as a seizure-related outcome in murine Atp1a3-related disease. ATP1A3-related syndromes are cardiac diseases and neurologic diseases. We provide guidance to identify patients potentially at higher risk of sudden cardiac death who may benefit from insertion of a pacemaker or implantable cardioverter-defibrillator.

Chondroid and Osseous Metaplasia of the Central Fibrous Body in Adolescent Hearts with Mutations in TNNI3 and TNNT2 genes.

The histological spectrum of the central fibrous body (CFB) of the heart, particularly in humans, is not fully characterized. Herein, we describe the presence of cartilage and bone within the CFB of 2 explanted heart specimens from patients with known mutation-driven cardiomyopathy involving the TNNI3 and TNNT2 genes, review the existing literature on the identified variants particularly TNNI3 (p.Asn185Thrfs*14) and TNNT2 (p.Arg141Trp), and provide insights into the plausible nature of such histopathological observation based on animal studies and the few reported cases in humans.

RBCK1-related disease: A rare multisystem disorder with polyglucosan storage, auto-inflammation, recurrent infections, skeletal, and cardiac myopathy-Four additional patients and a review of the current literature.

In this article, we report four new patients, from three kindreds, with pathogenic variants in RBCK1 and a multisystem disorder characterised by widespread polyglucosan storage. We describe the clinical presentation of progressive skeletal and cardiac myopathy, combined immunodeficiencies and auto-inflammation, illustrate in detail the histopathological findings in multiple tissue types, and report muscle MRI findings.

Farming without Glyphosate?

Recent statements from scientific organisations and court decisions have resulted in widespread public interest and concern over the safety of glyphosate, the most popular and effective herbicide used worldwide. Consequently, glyphosate-based products are under intense scrutiny from governments at all levels. Some jurisdictions have already banned or restricted its use, which will adversely impact international trade in bulk grain commmodities if glyphosate residues are detected. The possibility of farming without glyphosate is becoming an important issue facing the agri-food research and development sector. Contingency plans need to be formulated if that scenario becomes a reality. In this review, we briefly summarize international events that have led to this possible situation, describe current glyphosate usage in major agronomic field crops worldwide, outline possible alternatives to glyphosate in two agroregions and perform bioeconomic model scenarios of southern Australian broadacre cropping systems without the herbicide. Model predictions suggest that we can farm profitably without glyphosate by consistently utilizing key non-herbicidal weed management practices combined with robust pre-emergence soil residual herbicide treatments. However, maintaining low weed seed banks will be challenging. If the social license to use glyphosate is revoked, what other pesticides will soon follow?