Search

Kaposi sarcoma is a low-grade vascular neoplasm linked to the human herpesvirus 8, with the AIDS-associated epidemic variant being the most common and aggressive. Although Kaposi sarcoma more commonly affects the cutaneous tissues, lymph nodes, and visceral organs, it can also be present in ocular and ocular adnexal tissues. We report a case of a 58-year-old Indo-Caribbean woman living with AIDS who presented with a large upper eyelid mass that was clinically diagnosed as Kaposi sarcoma. After the recommencement of the patient's highly active antiretroviral therapy (HAART), the lesion showed marked regression, highlighting the critical role of HAART in the management of Kaposi sarcoma. This is the first documented case of AIDS-associated ocular Kaposi sarcoma in the Eastern Caribbean region and underscores the need to consider Kaposi sarcoma as a differential diagnosis in patients living with HIV/AIDS who present with ocular or ocular adnexal masses.

Objectives: This study reported the development of the Job-Related Uncertainty Stress Scale for Platform Workers (JUSSPW) and examined its reliability and validity., Methods: The research was conducted in two phases. In Study 1, item analysis and exploratory factor analysis were conducted on data from 343 platform riders (male:321; female:22; mean age:27.03±6.67) in Guangzhou, China. In Study 2, an additional 391 platform riders (male:328; female:63; mean age:30.36±4.49) were recruited. This phase involved conducting confirmatory factor analysis and assessing criterion-related validity by utilizing Uncertainty Stress Scale (USS-4), Maslach Burnout Inventory (MBI), and Job Satisfaction Inventory (JSI)., Results: The JUSSPW scale comprises 8 items under a unidimensional structure, covering four perspectives: work environment, interpersonal relationships, industry-specific characteristics, and personal development prospects, and explained 71.07% of the total variance. CFA results indicated that this one-factor model provided a good fit (χ²/df = 2.681, RMSEA = 0.066, CFI = 0.987, IFI = 0.987, GFI = 0.964, TLI = 0.982). This scale also demonstrated good convergent (AVE = 0.668, CR = 0.941) and criterion validity (AUC= 0.935). The total score of JUSSPW was significantly positively correlated with the USS-4 and MBI-EE scores, and remarkably negatively correlated with the JSI scores. Cronbach's alpha and split-half reliability were 0.939 and 0.935, respectively., Conclusions: These results suggested that this scale shows good reliability and validity and can be used as a sound measure to capture platform workers' job-related uncertainty stress. Limitation and implications were discussed., (© The Author(s) [2024]. Published by Oxford University Press.)

Dilated cardiomyopathy (DCM) is a leading cause of heart failure and cardiac transplantation. We report a genome-wide association study and multi-trait analysis of DCM (14,256 cases) and three left ventricular traits (36,203 UK Biobank participants). We identified 80 genomic risk loci and prioritized 62 putative effector genes, including several with rare variant DCM associations (MAP3K7, NEDD4L and SSPN). Using single-nucleus transcriptomics, we identify cellular states, biological pathways, and intracellular communications that drive pathogenesis. We demonstrate that polygenic scores predict DCM in the general population and modify penetrance in carriers of rare DCM variants. Our findings may inform the design of genetic testing strategies that incorporate polygenic background. They also provide insights into the molecular etiology of DCM that may facilitate the development of targeted therapeutics., Competing Interests: Competing interests: S.L.Z. has acted as a consultant for Health Lumen. A.H. and R.T.L. have received funding from Pfizer Inc. R.T.L. has performed paid consultancy for Health Lumen and Fitfile Ltd. J.S.W. has acted as a consultant for MyoKardia, Pfizer, Foresite Labs and Health Lumen and received institutional support from Bristol Myers Squibb and Pfizer Inc. P.C. has received personal fees for consultancies, outside the present work, for Amicus, Pfizer Inc., Owkin and Bristol Myers Squibb. M.-P.D. declares holding equity in Dalcor Pharmaceuticals, unrelated to this work. The authors who are affiliated with deCODE genetics/Amgen Inc. and Regeneron Pharmaceuticals declare competing financial interests as employees. The other authors declare no competing interests., (© 2024. The Author(s).)

Dilated cardiomyopathy (DCM) is a heart muscle disease that represents an important cause of morbidity and mortality, yet causal mechanisms remain largely elusive. Here, we perform a large-scale genome-wide association study and multitrait analysis for DCM using 9,365 cases and 946,368 controls. We identify 70 genome-wide significant loci, which show broad replication in independent samples and map to 63 prioritized genes. Tissue, cell type and pathway enrichment analyses highlight the central role of the cardiomyocyte and contractile apparatus in DCM pathogenesis. Polygenic risk scores constructed from our genome-wide association study predict DCM across different ancestry groups, show differing contributions to DCM depending on rare pathogenic variant status and associate with systolic heart failure across various clinical settings. Mendelian randomization analyses reveal actionable potential causes of DCM, including higher bodyweight and higher systolic blood pressure. Our findings provide insights into the genetic architecture and mechanisms underlying DCM and myocardial function more broadly., Competing Interests: Competing interests: P.T.E. has received sponsored research support from Bayer AG, IBM Health, Bristol Myers Squibb and Pfizer; he has consulted for Bayer AG, Novartis and MyoKardia. K.G.A. has received sponsored research support from Sarepta Therapeutics and Bayer AG, and reports a research collaboration with Novartis. Y.M.P. is involved in the development of therapies for DCM as an advisor to Forbion and Medical Director at ARMGO pharma and CMO at Phlox Therapeutics. P.C. reports personal fees for consultancies, outside the present work, for Amicus, OWKIN, Pfizer and SANOFI. J.S.W. has received research support from Bristol Myers Squibb, and has acted as a consultant for MyoKardia, Pfizer, Foresite Labs, Health Lumen and Tenaya Therapeutics. The remaining authors declare no competing interests., (© 2024. The Author(s).)

We describe a method for identifying and clustering diffraction vectors in four-dimensional (4-D) scanning transmission electron microscopy data to determine characteristic diffraction patterns from overlapping structures in projection. First, the data is convolved with a 4-D kernel, then diffraction vectors are identified and clustered using both density-based clustering and a metric that emphasizes rotational symmetries. The method works well for both crystalline and amorphous samples and in high- and low-dose experiments. A simulated dataset of overlapping aluminum nanocrystals provides performance metrics as a function of Poisson noise and the number of overlapping structures. Experimental data from an aluminum nanocrystal sample shows similar performance. For an amorphous Pd 77.5 Cu 6 Si 16.5 thin film, experiments measuring glassy structure show strong evidence of 4- and 6-fold symmetry structures. A significant background arises from the diffraction of overlapping structures. Quantifying this background helps to separate contributions from single, rotationally symmetric structures vs. apparent symmetries arising from overlapping structures in projection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The Rho kinases 1 and 2 (ROCK1/2) are serine-threonine specific protein kinases that control actin cytoskeleton dynamics. They are expressed in all cells throughout the body, including cardiomyocytes, smooth muscle cells and endothelial cells, and intimately involved in cardiovascular health and disease. Pharmacological ROCK inhibition is beneficial in mouse models of hypertension, atherosclerosis, and neointimal thickening that display overactivated ROCK. However, the consequences of endothelial ROCK signaling deficiency in vivo remain unknown. To address this issue, we analyzed endothelial cell (EC) specific ROCK1 and 2 deletions., Methods: We generated Cdh5-CreERT2 driven, tamoxifen inducible loss of function alleles of ROCK1 and ROCK2 and analyzed mouse survival and vascular defects through cellular, biochemical, and molecular biology approaches., Results: We observed that postnatal or adult loss of endothelial ROCK1 and 2 was lethal within a week. Mice succumbed to multi-organ hemorrhage that occurred because of loss of vascular integrity. ECs displayed deficient cytoskeletal actin polymerization that prevented focal adhesion formation and disrupted junctional integrity. Retinal sprouting angiogenesis was also perturbed, as sprouting vessels exhibited lack of polymerized actin and defective lumen formation. In a three-dimensional endothelial sprouting assay, combined knockdown of ROCK1/2 or knockdown or ROCK2 but not ROCK1 led to reduced sprouting, lumenization and cell polarization defects caused by defective actin and altered VE-cadherin dynamics. The isoform specific role of endothelial ROCK2 correlated with ROCK2 substrate specificity for FAK and LIMK. By analyzing single and three allele mutants we show that one intact allele of ROCK2 is sufficient to maintain vascular integrity in vivo ., Conclusion: Endothelial ROCK1 and 2 maintain junctional integrity and ensure proper angiogenesis and lumen formation. The presence of one allele of ROCK2 is sufficient to maintain vascular growth and integrity. These data indicate the need of careful consideration for the use of ROCK inhibitors in disease settings.

Artemesia tridentata is a foundational plant taxon in western North America and an important medicinal plant threatened by climate change. Low-cost fabrication of sensors is critical for developing large-area sensor networks for understanding and monitoring a range of environmental conditions. However, the availability of materials and manufacturing processes is still in the early stages, limiting the capacity to develop cost-effective sensors at a large scale. In this study, we demonstrate the fabrication of low-cost flexible sensors using laser-induced graphene (LIG); a graphitic material synthesized using a 450-nm wavelength bench top laser patterned onto polyimide substrates. We demonstrate the effect of the intensity and focus of the incident beam on the morphology and electrical properties of the synthesized material. Raman analyses of the synthesized LIG show a defect-rich graphene with a crystallite size in the tens of nanometers. This shows that the high level of disorder within the LIG structure, along with the porous nature of the material provide a good surface for gas adsorption. The initial characterization of the material has shown an analyte response represented by a change in resistance of up to 5% in the presence of volatile organic compounds (VOCs) that are emitted and detected by Artemisia species. Bend testing up to 100 cycles provides evidence that these sensors will remain resilient when deployed across the landscapes to assess VOC signaling in plant communities. The versatile low-cost laser writing technique highlights the promise of low-cost and scalable fabrication of LIG sensors for gas sensor monitoring., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Francis, Rektor, Valayil-Varghese, McKibben, Estrada, Forbey and Estrada.)

Background: Suicide and self-harm are global disease burden that contributes significantly to years of lost life and mortality. Despite the increasing rates of suicide and self-harm in Nigeria, this topic is understudied., Methods: A mixed-methods design was adopted. Study 1 interviewed n =  18 participants ( n =  11 clinicians; n =  5 patients with a history of self-harm and suicide ideation; and n =  2 caregivers). All interviews were audio-recorded, transcribed verbatim, and analyzed using IPA. Study 2 surveyed n =  562 non-clinical sample about their tolerance toward self-harm and the data was analyzed using One-way ANOVA in SPSS., Results: Study 1 qualitative findings showed substance use, perceived rejection and social isolation were considered predisposing factors for suicide and self-harm. Cultural and religious beliefs shaped help-seeking behaviours. Although Study 2 found no significant differences in demographic characteristics concerning public tolerance toward persons with a history of self-harm, 64% believed that individuals who died by suicide would face punishment after death; 51% believed that victims of attempted suicide are a source of shame to their families; and 33.8% agreed that dying by suicide is the correct behaviour., Conclusions: Patients with a history of self-harm and suicidal ideation consider family members and close friends as valuable sources of support. Due to the potential clinical implication of cultural and religious beliefs, as shown in the present study's findings, the authors recommend a co-development of culturally appropriate psychological intervention for persons with a history of self-harm and suicidal ideation to be tested in randomized control trials.

Background: Current prognostic tools do not reliably and objectively identify children with pneumonia at risk of a severe or life-threatening episode. Heparin-binding protein (HBP) is a host immune protein that is released in response to infection. We hypothesized that measuring HBP concentrations at hospital admission could help risk-stratify children with pneumonia and identify those at higher risk of an adverse prognosis., Methods: We evaluated the prognostic accuracy of HBP for predicting in-hospital mortality among children with respiratory distress, and whether HBP could improve the accuracy of validated composite clinical severity scores., Results: Of 778 Ugandan children under 5 years of age and presenting with clinically defined pneumonia, 60 (7.7%) died during hospital admission. HBP concentrations at presentation were significantly higher in children with fatal outcomes (median, 76 ng/mL [interquartile range {IQR}, 41-150]) compared to children who survived (median, 31 ng/mL [IQR, 18-57]) ( P < .001). Children with HBP >41 ng/mL on admission had an elevated risk of death (hazard ratio, 5.3 [95% confidence interval {CI}, 2.9-9.5]; P < .0001). In receiver operating characteristic (ROC) curve analysis, HBP concentrations distinguished between fatal and nonfatal outcomes (area under the ROC curve, 0.75 [95% CI, .66-.84]) and significantly improved the prediction provided by the Respiratory Index of Severity in Children, a composite clinical severity score ( P = .0026)., Conclusions: Measuring HBP at presentation could help identify children at risk of severe and fatal pneumonia. Adding HBP to clinical scores could improve the recognition and triage of children with pneumonia at risk of death., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Huntington's disease (HD) is an autosomal dominant disease caused by the expansion of cytosine-adenine-guanine (CAG) repeats in one copy of the HTT gene (mutant HTT, mHTT). The unaffected HTT gene encodes wild-type HTT (wtHTT) protein, which supports processes important for the health and function of the central nervous system. Selective lowering of mHTT for the treatment of HD may provide a benefit over nonselective HTT-lowering approaches, as it aims to preserve the beneficial activities of wtHTT. Targeting a heterozygous single-nucleotide polymorphism (SNP) where the targeted variant is on the mHTT gene is one strategy for achieving allele-selective activity. Herein, we investigated whether stereopure phosphorothioate (PS)- and phosphoryl guanidine (PN)-containing oligonucleotides can direct allele-selective mHTT lowering by targeting rs362273 (SNP3). We demonstrate that our SNP3-targeting molecules are potent, durable, and selective for mHTT in vitro and in vivo in mouse models. Through comparisons with a surrogate for the nonselective investigational compound tominersen, we also demonstrate that allele-selective molecules display equivalent potency toward mHTT with improved durability while sparing wtHTT. Our preclinical findings support the advancement of WVE-003, an investigational allele-selective compound currently in clinical testing (NCT05032196) for the treatment of patients with HD., Competing Interests: N.I., Y.L., M.F.-K., A.M., W.C.T., K.T., N.K., A.A., K.B., J.D.S., A.L., X.S.H., H.G.J., P.K., F.L., K.L., R.L., M., J.M., Q.P., E.P.-E., M.S., P.S.P., S.S., H.Y., A.Z., C.F., M.B., E.D., and C.V. were employees of Wave Life Sciences during the completion of this work. M. is currently an employee of Stoke Therapeutics. G.L.V. is on the board of directors and is a consultant and shareholder for Wave Life Sciences., (© 2024 The Author(s).)

Infantile hemangiomas are commonly encountered at all levels of medical practice. Clinicians should be aware of their typical clinical history and findings in order to expedite early diagnosis and management. It is also necessary to be aware of differential diagnoses that may mimic infantile hemangiomas but have a more concerning prognosis. The objective of this report is to describe the clinical case of one such mimic, dermatofibrosarcoma protuberans. This report highlights key clinical findings of infantile hemangiomas, while also identifying "red flags" that necessitate urgent additional investigations and referral to a multidisciplinary team. Additionally, key features in the management of both infantile hemangiomas and extremity masses are discussed., Competing Interests: Disclosures: The authors declare no conflict of interest or financial disclosures., (© 2024 HMP Global. All Rights Reserved. Any views and opinions expressed are those of the author(s) and/or participants and do not necessarily reflect the views, policy, or position of ePlasty or HMP Global, their employees, and affiliates.)

Background: In the context of drug prohibition, potential adulteration and variable purity pose additional health risks for people who use drugs, with these risks often compounded by the outdoor music festival environment. Ahead of the imminent implementation of drug checking services in Queensland, Australia, this study aims to characterise this problem using triangulated survey and wastewater data to understand self-reported and detected drug use among attendees of a multi-day Queensland-based music festival in 2021 and 2022., Methods: We administered an in-situ survey focusing on drug use at the festival to two convenience samples of 136 and 140 festival attendees in 2021 and 2022 respectively. We compared survey findings to wastewater collected concurrently from the festival's site-specific wastewater treatment plant, which was analysed using Liquid Chromatography Tandem Mass Spectrometry., Results: Most survey respondents (82 % in 2021, 92 % in 2022) reported using or intending to use an illicit drug at the festival. Some respondents reported potentially risky drug use practices such as using drugs found on the ground (2 % in 2021, 4 % in 2022). Substances detected in wastewater but not surveys include MDEA, mephedrone, methylone, 3-MMC, alpha-D2PV, etizolam, eutylone, and N,N-dimethylpentylone., Conclusion: Many substances detected in wastewater but not self-reported in surveys likely represent substitutions or adulterants. These findings highlight the benefits of drug checking services to prevent harms from adulterants and provide education on safer drug use practices. These findings also provide useful information on socio-demographic characteristics and drug use patterns of potential users of Queensland's future drug checking service., Competing Interests: Declaration of competing interest The Loop Australia is a not-for-profit organisation aiming to develop the sustainable provision of drug checking services in Australia. Cameron Francis is the paid CEO of The Loop Australia. Fiona Measham is an unpaid board member of The Loop Australia and the unpaid director of The Loop UK (a non-profit non-government organisation that delivers drug checking services). All other authors affiliated with The Loop Australia are unpaid volunteers., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: One in every three women worldwide experiences postnatal depression after childbirth, with long-term negative consequences on their children. The mainstream mental healthcare provision for British mothers of African/Caribbean origin is mostly unsuccessful due to a lack of culturally appropriate care., Methods: The study adopts a mixed-methods randomised controlled trial (RCT) design. A 12-session (60 minutes each) of online Learning Through Play plus Culturally adapted Cognitive Behaviour Therapy (LTP+CaCBT) intervention was employed for treating postnatal depression in comparison with psychoeducation (PE). Participants aged 19-53 were screened for depression using the Patient Health Questionnaire (PHQ-9). N=130 participants who scored >5 on PHQ-9 were randomised into LTP+CaCBT (n=65) or PE (n=65) groups. N=12 focus groups (LTP+CaCBT, n=6; PE, n=6) and n=15 individual interviews (LTP+CaCBT, n=8; PE, n=7) were conducted, transcribed verbatim and analysed., Results: Satisfaction with intervention (LTP+CaCBT, 72.9%; PE, 65.2%); retention rates (LTP+CaCBT, 91%; PE, 71%); reduction in postnatal depression was higher in LTP+CaCBT on PHQ-9 Md=1.00 with z= -4.046; compared to PE, Md=1.00 with z= -1.504. Both groups showed reduced levels of anxiety on GAD-7 with no significant difference. Emerging themes from the qualitative findings showed increased positive moods, reduced worries about parenting difficulties and the facilitative role of remote intervention., Conclusions: LTP+CaCBT intervention is culturally appropriate and acceptable and reduces postnatal depression in British mothers of African/Caribbean origin. A fully powered RCT is recommended to evaluate the clinical and cost-effectiveness of LTP+CaCBT, including the child's outcomes compared with routine treatment as usual., Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT04820920., Competing Interests: NH has been a past Trustee of the Pakistan Institute of Living and Learning (PILL), Abaseen Foundation UK, Lancashire Mind UK and Manchester Global Foundation (MGF). He is an executive member of the Academic Faculty at the Royal College of Psychiatrists, London. He is an NIHR Senior Investigator. He has attended educational events organized by various pharmaceutical industries. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jidong, Ike, Murshed, Francis, Mwankon, Jidong, Pwajok, Nyam and Husain.)

Background: Self-harm and suicidal ideation are increasing public health concerns globally and are paramount in Africa. Therefore, a review of suicidal ideation and self-harm interventions would be beneficial in identifying culturally appropriate interventions for the African context., Method: The Population, phenomenon of Interest and Context (PICo) model was adopted to formulate the review strategy. Thus, the Population (Africans), phenomenon of Interest (intervention) and Context (self-harm and suicidal ideation). We used this PICo strategy which is a modified version of PICO for qualitative studies. Framework with Boolean operators (AND/OR/NOT) was further used to ensure rigor through search terms such as ("Suicide" OR "suicidal ideation") AND ("Intervention" OR "Treatment" OR "Therapy" OR "Psychological" OR "Psychosocial" OR "Culturally adapted") AND "Africa" OR "African countries." Six databases were searched (Embase, PsycINFO, ProQuest Central, Cochrane Controlled Trials Register, Medline, and Web of Science) for published articles between 2000 and March 2023. N =  12 studies met the inclusion criteria, and the relevant data extracted were synthesized and thematically analyzed. The review protocol was pre-registered on the PROSPERO Registry (no. CRD42021283795)., Results: N =  12 studies met the inclusion criteria, and the following themes emerged from the synthesized literature and analyses of current African approaches to curbing self-harm and suicidal ideation: (a) Western medical and compassion-focused intervention (b) the helpful role of traditional healing and healers (c) psychoeducation and self-help techniques (d) use of technology and a nation-wide approach., Conclusion: Self-harm and suicidal ideation are global health concerns. To address this health concern in Africa, the authors recommend culturally adapted psychological interventions to be tested via randomized control trials.

Purpose: To investigate the design and location of supporting structures on the marginal and internal gap of interim restorations., Materials and Methods: A mandibular right first molar resin tooth was prepared for a full coverage crown and scanned using a laboratory scanner (3Shape D900). The scanned data were converted into standard tessellation language (STL) format and an indirect prosthesis was designed using computer-aided design (CAD) software (exocad DentalCAD). The STL file was used to fabricate a total of 60 crowns with a 3D printer (EnvisionTEC Vida HD). The crowns were printed using E-Dent C&B MH resin and divided into 4 groups based on four different support structure designs, including supports on the occlusal (0° group), buccal and occlusal (45° group), buccal (90° group), and a new design consisting of horizontal bars placed on all surfaces and line angles (Bar) (n = 15). The silicone replica technique was used to determine the gap discrepancy. Fifty measurements were obtained for each specimen to examine the marginal and internal gaps by using a digital microscope (Olympus SZX16) at ×70 magnification. Additionally, the marginal discrepancy at different locations of the tested crowns, including buccal (B), lingual (L), mesial (M), and distal (D), as well as the maximum and minimum marginal gap intervals among groups, were analyzed. The collected data were analyzed using factorial ANOVA, followed by the Tukey HSD test for multiple comparisons (a = 0.05)., Results: There was a significant difference in marginal and internal gaps among the groups (p < 0.001). The buccal placement supports (90° group) had the least marginal and internal discrepancies (p < 0.001). The new design group showed the highest marginal and internal gap. The marginal discrepancy in different locations of the tested crowns (B, L, M, D) was found to be significantly different among the groups (p < 0.001). The mesial margin of the Bar group had the largest marginal gap, whereas the buccal margin of the 90° group had the lowest marginal gap. The new design had a significantly smaller difference between the maximum and minimum marginal gap intervals than other groups (p < 0.001)., Conclusion: The location and design of the supporting structures affected the marginal and internal gaps of an interim crown. The buccal placement of supporting bars (90° printing orientation) showed the smallest mean internal and marginal discrepancies., (© 2023 by the American College of Prosthodontists.)

The current letter to the editor describes the presence of RNA byproducts in small-scale in vitro transcription (IVT) reactions as evaluated by capillary gel electrophoresis, asymmetric flow field flow fractionation, immunoblotting, cell-free translation assays, and in IFN reporter cells. We compare standard T7 RNA polymerase (RNAP) based IVT reactions to two recently described protocols employing either urea supplementation or using the VSW3 RNAP. Our results indicate that urea supplementation yields considerably less RNA byproducts and positively affects the overall number of full-length transcripts. In contrast, VSW3 IVT reactions demonstrated a low yield and generated a higher fraction of truncated transcripts. Lastly, both urea mRNA and VSW3 mRNA elicited considerably less IFN responses after transfection in mouse macrophages.

To assess skin color change in alligators, we maintained animals in differently lighted environments and also measured skin colors in an ontogenetic series of wild animals. Juvenile alligators maintained in black enclosures exhibited a gradual lightening of skin color when shifted to white enclosures, and these observed changes were reversible. A histological examination of the skins of alligators maintained in dark tanks showed that the dermis exhibited a dense layer of pigmented cells, while samples from the same animals in light environments exhibited a more diffuse pigmented layer. As alligators grow, they exhibit an ontogenetic loss of stripes that may aid in crypsis and predation. Hatchlings have intense black and yellow vertical stripes that darken with age; adults are a more homogenous black/gray color. Since alligators live in temperate climates and adults have lower surface area/volume ratios, which can be detrimental for the absorption of radiant energy, the darker color of larger animals may also aid in thermoregulation. Alligators at the northern end of their range, with colder climates, exhibited darker skin tones, and the ontogenetic extinction of stripes occurred at a more accelerated rate compared to animals in southern, warmer regions, supporting the idea that latitude-dependent ontogenetic color shift has a role in thermoregulation.

Conductive and biofriendly gold nanomaterial inks are highly desirable for printed electronics, biosensors, wearable electronics, and electrochemical sensor applications. Here, we demonstrate the scalable synthesis of stable gold nanoparticle inks with low-temperature sintering using simple chemical processing steps. Multiprinter compatible aqueous gold nanomaterial inks were formulated, achieving resistivity as low as ∼10 -6 Ω m for 400 nm thick films sintered at 250 °C. Printed lines with a resolution of <20 μm and minimal overspray were obtained using an aerosol jet printer. The resistivity of the printed patterns reached ∼9.59 ± 1.2 × 10 -8 Ω m after sintering at 400 °C for 45 min. Our aqueous-formulated gold nanomaterial inks are also compatible with inkjet printing, extending the design space and manufacturability of printed and flexible electronics where metal work functions and chemically inert films are important for device applications., Competing Interests: The authors declare the following competing financial interest(s): D.E. and H.S. declare competing interests with INFlex Labs, LLC, the company commercializing multijet gold inks., (© 2023 The Authors. Published by American Chemical Society.)

Tumor-associated immune cells play a crucial role in cancer progression. Myeloid-derived suppressor cells (MDSCs), for example, are immature innate immune cells that infiltrate the tumor to exert immunosuppressive activity and protect cancer cells from the host's immune system and/or cancer-specific immunotherapies. While tumor-associated immune cells have emerged as a promising therapeutic target, efforts to counter immunosuppression within the tumor niche have been hampered by the lack of approaches that selectively target the immune cell compartment of the tumor, to effectively eliminate "tumor-protecting" immune cells and/or drive an "anti-tumor" phenotype. Here we report on a novel nanotechnology-based approach to target tumor-associated immune cells and promote "anti-tumor" responses in a murine model of breast cancer. Engineered extracellular vesicles (EVs) decorated with ICAM-1 ligands and loaded with miR-146a and Glut1 , were biosynthesized ( in vitro or in vivo ) and administered to tumor-bearing mice once a week for up to 5 weeks. The impact of this treatment modality on the immune cell compartment and tumor progression was evaluated via RT-qPCR, flow cytometry, and histology. Our results indicate that weekly administration of the engineered EVs ( i.e. , ICAM-1-decorated and loaded with miR-146a and Glut1 ) hampered tumor progression compared to ICAM-1-decorated EVs with no cargo. Flow cytometry analyses of the tumors indicated a shift in the phenotype of the immune cell population toward a more pro-inflammatory state, which appeared to have facilitated the infiltration of tumor-targeting T cells, and was associated with a reduction in tumor size and decreased metastatic burden. Altogether, our results indicate that ICAM-1-decorated EVs could be a powerful platform nanotechnology for the deployment of immune cell-targeting therapies to solid tumors.

Three-dimensional (3D) tissue engineering (TE) is a prospective treatment that can be used to restore or replace damaged musculoskeletal tissues, such as articular cartilage. However, current challenges in TE include identifying materials that are biocompatible and have properties that closely match the mechanical properties and cellular microenvironment of the target tissue. Visualization and analysis of potential 3D porous scaffolds as well as the associated cell growth and proliferation characteristics present additional problems. This is particularly challenging for opaque scaffolds using standard optical imaging techniques. Here, we use graphene foam (GF) as a 3D porous biocompatible substrate, which is scalable, reproducible, and a suitable environment for ATDC5 cell growth and chondrogenic differentiation. ATDC5 cells are cultured, maintained, and stained with a combination of fluorophores and gold nanoparticles to enable correlative microscopic characterization techniques, which elucidate the effect of GF properties on cell behavior in a 3D environment. Most importantly, the staining protocol allows for direct imaging of cell growth and proliferation on opaque scaffolds using X-ray MicroCT, including imaging growth of cells within the hollow GF branches, which is not possible with standard fluorescence and electron microscopy techniques.

Introduction: Research supports the feasibility and acceptance of drug checking among nightlife and festival attendees. Interest in expanding drug checking to other groups of people who use drugs, including those who inject drugs, has grown. However, understanding the acceptability and feasibility of drug checking among specific cohorts, like anabolic-androgenic steroids (AAS) consumers, remains a research gap. This study explores AAS consumers' perspectives on drug checking and service preferences, aiding the preparation for drug checking delivery in Queensland, Australia., Methods: A purposive sampling technique was used to recruit 15 AAS consumers (9 males, 6 females; Mage = 36.80 years, SD = 6.12) from Australia. One-on-one semi-structured qualitative interviews were conducted with questions exploring participants' views on drug checking/testing and their preferences for AAS analysis. Thematic analysis was conducted with final themes established through iterative consensus., Results: Consumers expressed frustration with the prevailing stereotypes, social stigma, and the perception of criminality associated with the use of AAS. There was a strong dependence on personal connections and trusted suppliers, with coaches exerting significant influence. Participants expressed concerns about the widespread availability of counterfeit products and underground operations. The act of using unknown AAS was likened to a game of Russian roulette, underscoring the importance of obtaining accurate information and access to reliable drug checking services. Consumers expressed a preference for a web-based platform that enables individuals to access their own test results while contributing to a comprehensive database of brand-specific testing outcomes., Discussion: AAS consumers recognise the significance of monitoring their AAS use and seek a service that can not only assist them in making informed decisions regarding AAS usage but also potentially contribute to the knowledge of the wider AAS-consuming community. These findings underscore the importance of tailored education, drug checking services, and harm reduction measures to address the diverse needs of AAS consumers., Competing Interests: Declaration of Competing Interest Dr's Piatkowski, Dunn, Puljevic, and Prof Ferris, are volunteer members of The Loop Australia, which is a national organisation for drug checking and drug checking research. Cameron Francis is the CEO of The Loop Australia., (Copyright © 2023. Published by Elsevier B.V.)

Background: Obstructive sleep apnoea (OSA) involves repeated breathing pauses during sleep due to upper airway obstruction. It causes excessive daytime sleepiness and has other health impacts. Continuous positive airway pressure (CPAP) therapy is effective first line treatment for moderate to severe OSA. Unfortunately, many patients have difficulty tolerating CPAP and pressure intolerance is probably an important contributing factor. Mandibular advancement devices (MAD) are an alternative to CPAP. They are worn in the mouth during sleep to reduce airway obstruction. There is some evidence that, when used in combination with CPAP, MADs improve airway anatomy enough to reduce the CPAP pressure required to treat OSA and that this combination therapy could improve CPAP adherence., Methods: Consecutive patients starting on CPAP for moderate to severe OSA will be recruited at a regional NHS sleep service. Patients with high CPAP pressure requirements after initial titration, who satisfy all entry criteria and consent to participate, will undertake a 2-arm randomised crossover trial. The arms will be (i) standalone CPAP and (ii) CPAP + MAD therapy. Each arm will last 12 weeks, including 2 weeks acclimatisation. CPAP machines will be auto-titrating and with facility for data download, so the impact of MAD on CPAP pressure requirements and CPAP adherence can be easily measured. The primary outcome will be CPAP adherence. Secondary outcomes will include measures of OSA severity, patient-reported outcome measures including subjective daytime sleepiness, quality of life, and treatment preference at the trial exit and health service use. Cost-effectiveness analyses will be undertaken., Discussion: If the intervention is shown to be effective and cost-effective in improving adherence in this standard CPAP-eligible OSA patient population it would be relatively straightforward to introduce into existing OSA treatment pathways, within the wider NHS and more widely. Both MAD and CPAP are already used by sleep services so their combination would require only minor adjustments to existing clinical pathways. It would be straightforward to disseminate the results of the study through regional, national, and international respiratory meetings. The health economics analysis would provide cost-effectiveness data to inform service planning and clinical guidelines through policy briefing papers, including those by NICE and SIGN., Trial Registration: PAPMAT was registered with ISRCTN prior to recruitment beginning (ISRCTN Registry 2021): https://www.isrctn.com/ISRCTN33966032 . Registered on 17th November 2021., (© 2023. The Author(s).)

Renal osteodystrophy (ROD) is a disorder of bone metabolism that affects virtually all patients with chronic kidney disease (CKD) and is associated with adverse clinical outcomes including fractures, cardiovascular events, and death. In this study, we showed that hepatocyte nuclear factor 4α (HNF4α), a transcription factor mostly expressed in the liver, is also expressed in bone, and that osseous HNF4α expression was dramatically reduced in patients and mice with ROD. Osteoblast-specific deletion of Hnf4α resulted in impaired osteogenesis in cells and mice. Using multi-omics analyses of bones and cells lacking or overexpressing Hnf4α1 and Hnf4α2, we showed that HNF4α2 is the main osseous Hnf4α isoform that regulates osteogenesis, cell metabolism, and cell death. As a result, osteoblast-specific overexpression of Hnf4α2 prevented bone loss in mice with CKD. Our results showed that HNF4α2 is a transcriptional regulator of osteogenesis, implicated in the development of ROD.

Introduction: S taphylococcus epidermidis is a commensal bacterium ubiquitously present on human skin. This species is considered as a key member of the healthy skin microbiota, involved in the defense against pathogens, modulating the immune system, and involved in wound repair. Simultaneously, S. epidermidis is the second cause of nosocomial infections and an overgrowth of S. epidermidis has been described in skin disorders such as atopic dermatitis. Diverse isolates of S. epidermidis co-exist on the skin. Elucidating the genetic and phenotypic specificities of these species in skin health and disease is key to better understand their role in various skin conditions. Additionally, the exact mechanisms by which commensals interact with host cells is partially understood. We hypothesized that S. epidermidis isolates identified from different skin origins could play distinct roles on skin differentiation and that these effects could be mediated by the aryl hydrocarbon receptor (AhR) pathway., Methods: For this purpose, a library of 12 strains originated from healthy skin (non-hyperseborrheic (NH) and hyperseborrheic (H) skin types) and disease skin (atopic (AD) skin type) was characterized at the genomic and phenotypic levels., Results and Discussion: Here we showed that strains from atopic lesional skin alter the epidermis structure of a 3D reconstructed skin model whereas strains from NH healthy skin do not. All strains from NH healthy skin induced AhR/OVOL1 path and produced high quantities of indole metabolites in co-culture with NHEK; especially indole-3-aldehyde (IAld) and indole-3-lactic acid (ILA); while AD strains did not induce AhR/OVOL1 path but its inhibitor STAT6 and produced the lowest levels of indoles as compared to the other strains. As a consequence, strains from AD skin altered the differentiation markers FLG and DSG1. The results presented here, on a library of 12 strains, showed that S. epidermidis originated from NH healthy skin and atopic skin have opposite effects on the epidermal cohesion and structure and that these differences could be linked to their capacity to produce metabolites, which in turn could activate AHR pathway. Our results on a specific library of strains provide new insights into how S. epidermidis may interact with the skin to promote health or disease., Competing Interests: Authors LL, CC, CF, SM, AG, DB and LA were employed by the company L’Oréal Research and Innovation, Aulnay-sous-Bois. JV was employed by iMEAN, Toulouse, France. L’Oréal Research and Innovation, as funder, has been involved in the decision to submit the study for publication., (Copyright © 2023 Landemaine, Da Costa, Fissier, Francis, Morand, Verbeke, Michel, Briandet, Sokol, Gueniche, Bernard, Chatel, Aguilar, Langella, Clavaud and Richard.)

Background: Women are likely to suffer from maternal depression due to childbirth difficulties and parenting responsibilities, leading to long-term negative consequences on their children and families. British mothers of African/Caribbean origin uptake of mental healthcare is low due to the lack of access to culturally appropriate care., Methods: A mixed-methods randomized controlled feasibility trial was adopted to test the appropriateness and acceptability of Learning Through Play plus Culturally adapted Cognitive Behaviour Therapy (LTP+CaCBT) for treating maternal depression compared with Psychoeducation (PE). Mothers (N = 26) aged 20-55 were screened for depression using the Patient Health Questionnaire (PHQ-9). Those who scored >5 on PHQ-9 were further interviewed using the Revised Clinical Interview Schedule to confirm the diagnosis and randomized into LTP+CaCBT (n = 13) or PE (n = 13) groups. Assessments were taken at baseline, end of the intervention at 3- and 6-months post-randomization. N = 2 focus groups (LTP+CaCBT, n = 12; PE, n = 7) and N = 8 individual interviews were conducted (LTP+CaCBT, n = 4; PE, n = 4)., Results: The LTP+CaCBT group showed higher acceptability, feasibility and satisfaction levels than the PE group. Participants experienced the intervention as beneficial to their parenting skills with reduced depression and anxiety in the LTP+CaCBT compared to the PE group., Conclusions: This is the first feasibility trial of an integrated online parenting intervention for British African and Caribbean mothers. The results indicated that culturally adapted LTP+CaCBT is acceptable and feasible. There is a need to study the clinical and cost-effectiveness of LTP+CaCBT in an appropriately powered randomized control trial and include the child's outcomes., Trial Registration: www., Clinicaltrials: gov (no. NCT04820920)., (© 2022 The Authors. Clinical Psychology & Psychotherapy published by John Wiley & Sons Ltd.)

Background: Cardiovascular disease is a major cause of excess mortality in people with schizophrenia. Several factors are responsible, including lifestyle and metabolic effects of antipsychotics. However, variations in cardiac structure and function are seen in people with schizophrenia in the absence of cardiovascular disease risk factors and after accounting for lifestyle and medication. Therefore, we aimed to explore whether shared genetic causes contribute to these cardiac variations., Methods: For this observational study, we used data from the UK Biobank and included White British or Irish individuals without diagnosed schizophrenia with variable polygenic risk scores for the condition. To test the association between polygenic risk score for schizophrenia and cardiac phenotype, we used principal component analysis and regression. Robust regression was then used to explore the association between the polygenic risk score for schizophrenia and individual cardiac phenotypes. We repeated analyses with fibro-inflammatory pathway-specific polygenic risk scores for schizophrenia. Last, we investigated genome-wide sharing of common variants between schizophrenia and cardiac phenotypes using linkage disequilibrium score regression. The primary outcome was principal component regression., Findings: Of 33 353 individuals recruited, 32 279 participants had complete cardiac MRI data and were included in the analysis, of whom 16 625 (51·5%) were female and 15 654 (48·5%) were male. 1074 participants were excluded on the basis of incomplete cardiac MRI data (for all phenotypes). A model regressing polygenic risk scores for schizophrenia onto the first five cardiac principal components of the principal components analysis was significant (F=5·09; p=0·00012). Principal component 1 captured a pattern of increased cardiac volumes, increased absolute peak diastolic strain rates, and reduced ejection fractions; polygenic risk scores for schizophrenia and principal component 1 were negatively associated (β=-0·01 [SE 0·003]; p=0·017). Similar to the principal component analysis results, for individual cardiac phenotypes, we observed negative associations between polygenic risk scores for schizophrenia and indexed right ventricular end-systolic volume (β=-0·14 [0·04]; p=0·0013, p FDR =0·015), indexed right ventricular end-diastolic volume (β=-0·17 [0·08]); p=0·025; p FDR =0·082), and absolute longitudinal peak diastolic strain rates (β=-0·01 [0·003]; p=0·0024, p FDR =0·015), and a positive association between polygenic risk scores for schizophrenia and right ventricular ejection fraction (β=0·09 [0·03]; p=0·0041, p FDR =0·015). Models examining the transforming growth factor-β (TGF-β)-specific and acute inflammation-specific polygenic risk scores for schizophrenia found significant associations with the first five principal components (F=2·62, p=0·022; F=2·54, p=0·026). Using linkage disequilibrium score regression, we observed genetic overlap with schizophrenia for right ventricular end-systolic volume and right ventricular ejection fraction (p=0·0090, p=0·0077)., Interpretation: High polygenic risk scores for schizophrenia are associated with decreased cardiac volumes, increased ejection fractions, and decreased absolute peak diastolic strain rates. TGF-β and inflammatory pathways might be implicated, and there is evidence of genetic overlap for some cardiac phenotypes. Reduced absolute peak diastolic strain rates indicate increased myocardial stiffness and diastolic dysfunction, which increases risk of cardiac disease. Thus, genetic risk for schizophrenia is associated with cardiac structural changes that can worsen cardiac outcomes. Further work is required to determine whether these associations are specific to schizophrenia or are also seen in other psychiatric conditions., Funding: National Institute for Health Research, Maudsley Charity, Wellcome Trust, Medical Research Council, Academy of Medical Sciences, Edmond J Safra Foundation, British Heart Foundation., Competing Interests: Declaration of interests TP has participated in speaker meetings organised by Lundbeck, Otsuka, Sunovion, CNX Therapeutics, Schwabe Pharma, Janssen, and Recordati. RAM has participated in speaker meetings organised by Otsuka and Janssen. DPO'R has received grant funding and honoraria from Bayer AG. JF has received honoraria or consultancy fees from Atheneum, Informa, Nutritional Medicine Institute, ParachuteBH, Richmond Foundation, and Nirakara. PMM has received consultancy fees from Roche and Biogen, honoraria or speakers' fees from Novartis and Biogen, and research or educational funds from Biogen and Novartis. ODH is a part-time employee and stockholder of H Lundbeck A/S and has received investigator-initiated research funding from or participated in advisory or speaker meetings organised by Angellini, Autifony, Biogen, Boehringer-Ingelheim, Eli Lilly, Heptares, Global Medical Education, Invicro, Janssen, Lundbeck, Neurocrine, Otsuka, Sunovion, Rand, Recordati, Roche, and Viatris/Mylan. All other authors declare no competing interests., (Copyright © 2023 Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Glioma-induced immune dysregulation of the hematopoietic system has been described in a limited number of studies. In this study, our group further demonstrates that gliomas interrupt the cellular differentiation programming and outcomes of hematopoietic stem and progenitor cells (HSPCs) in the bone marrow. HSPCs from glioma-bearing mice are reprogrammed and driven towards expansion of myeloid lineage precursors and myeloid-derived suppressor cells (MDSCs) in secondary lymphoid organs. However, we found this expansion is reversed by immunotherapy. Adoptive cellular therapy (ACT) has been demonstrably efficacious in multiple preclinical models of central nervous system (CNS) malignancies, and here we describe how glioma-induced dysfunction is reversed by this immunotherapeutic platform., Methods: The impact of orthotopic KR158B-luc glioma on HSPCs was evaluated in an unbiased fashion using single cell RNAseq (scRNAseq) of lineage - cells and phenotypically using flow cytometry. Mature myeloid cell frequencies and function were also evaluated using flow cytometry. Finally, ACT containing total body irradiation, tumor RNA-pulsed dendritic cells, tumor-reactive T cells and HSPCs isolated from glioma-bearing or non-tumor-bearing mice were used to evaluate cell fate differentiation and survival., Results: Using scRNAseq, we observed an altered HSPC landscape in glioma-bearing versus non-tumor-bearing mice . In addition, an expansion of myeloid lineage subsets, including granulocyte macrophage precursors (GMPs) and MDSCs, were observed in glioma-bearing mice relative to non-tumor-bearing controls. Furthermore, MDSCs from glioma-bearing mice demonstrated increased suppressive capacity toward tumor-specific T cells as compared with MDSCs from non-tumor-bearing hosts. Interestingly, treatment with ACT overcame these suppressive properties. When HSPCs from glioma-bearing mice were transferred in the context of ACT, we observed significant survival benefit and long-term cures in orthotopic glioma models compared with mice treated with ACT using non-glioma-bearing HSPCs., Competing Interests: Competing interests: CTF and DM hold interest in iOncologi, Inc, a biotechnology company focused on immuno-oncology. Other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Bipolar Disorders (BDs) are chronic mental health disorders that often result in functional impairment and contribute significantly to the disability-adjusted life years (DALY). BDs are historically under-researched compared to other mental health disorders, especially in Sub-Saharan Africa and Nigeria., Design: We adopted a mixed-methods design. Study 1 examined the public knowledge of BDs in relation to sociodemographic outcomes using quantitative data whilst Study 2 qualitatively assessed the lived experiences of patients with BDs, clinicians, and family caregivers., Methods: In Study 1, a non-clinical sample of n = 575 participants responded to a compact questionnaire that examined their knowledge of BDs and how they relate to certain sociodemographic variables. One-way ANOVA was used to analyse quantitative data. Study 2 interviewed N = 15 participants (n = 5 patients with BDs; n = 7 clinicians; n = 3 family caregivers). These semi-structured interviews were audio-recorded, transcribed, and thematically analysed., Results: In Study 1, findings showed no statistically significant differences, suggesting low awareness of BDs, especially among vulnerable populations such as young people and older adults. However, there was a trajectory in increased knowledge of BDs among participants between the ages of 25-44 years and part-time workers compared to other ages and employment statuses. In Study 2, qualitative findings showed that BDs are perceived to be genetically and psycho-socially induced by specific lived experiences of patients and their family caregivers. Although psychotropic medications and psychotherapy are available treatment options in Nigeria, cultural and religious beliefs were significant barriers to treatment uptake., Conclusions: This study provides insight into knowledge and beliefs about BDs, including the lived experiences of patients with BDs, their caregivers and clinicians in Nigeria. It highlights the need for further studies assessing Nigeria's feasibility and acceptability of culturally adapted psychosocial interventions for patients with BDs., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Prostate Cancer screening based on manual palpation is subjective. Robotic palpation systems can objectively acquire stiffness conditions of the prostate., Methods: A 2DoF cable driven robotic system for prostate palpation is proposed. An indirect method to estimate the contact force based on cable tension observation is presented. Kinematic models and a joint angle estimation method to determine the tip position of the probe are derived. Positioning accuracy was verified using an optical marker tracking system and by displacement measurement, respectively. The contact force estimation method was validated on silicone phantom samples., Results: A good consistence between the estimated and measured contact force was observed. The contact force was correlated with the elastic modulus of each silicone phantom. There was also a good agreement between the theoretical and the measured tip position., Conclusion: In the proposed palpation system, the indirect contact force estimation method is viable and holds potential for the stiffness assessment of the prostate. The tip position vital for palpation can be determined through estimated joint angles., (© 2022 The Authors. The International Journal of Medical Robotics and Computer Assisted Surgery published by John Wiley & Sons Ltd.)

Melanoma brain metastasis (MBM) is linked to poor prognosis and low overall survival. We hypothesized that melanoma circulating tumor cells (CTCs) possess a gene signature significantly expressed and associated with MBM. Employing a multi-pronged approach, we provide first-time evidence identifying a common CTC gene signature for ribosomal protein large/small subunits (RPL/RPS) which associate with MBM onset and progression. Experimental strategies involved capturing, transcriptional profiling and interrogating CTCs, either directly isolated from blood of melanoma patients at distinct stages of MBM progression or from CTC-driven MBM in experimental animals. Second, we developed the first Magnetic Resonance Imaging (MRI) CTC-derived MBM xenograft model (MRI-MBM CDX) to discriminate MBM spatial and temporal growth, recreating MBM clinical presentation and progression. Third, we performed the comprehensive transcriptional profiling of MRI-MBM CDXs, along with longitudinal monitoring of CTCs from CDXs possessing/not possessing MBM. Our findings suggest that enhanced ribosomal protein content/ribogenesis may contribute to MBM onset. Since ribosome modifications drive tumor progression and metastatic development by remodeling CTC translational events, overexpression of the CTC RPL/RPS gene signature could be implicated in MBM development. Collectively, this study provides important insights for relevance of the CTC RPL/RPS gene signature in MBM, and identify potential targets for therapeutic intervention to improve patient care for melanoma patients diagnosed with or at high-risk of developing MBM., Competing Interests: Conflicts of Interest: Authors declare no conflict of interest.

Densely spaced four-dimensional scanning transmission electron microscopy (4D STEM) analyzed using correlation symmetry coefficients enables large area mapping of approximate rotational symmetries in amorphous materials. Here, we report the effects of Poisson noise, limited electron counts, probe coherence, reciprocal space sampling, and the probe-sample interaction volume on 4D STEM symmetry mapping experiments. These results lead to an experiment parameter envelope for high quality, high confidence 4D STEM symmetry mapping. We also establish a direct link between the symmetry coefficients and approximate rotational symmetries of nearest-neighbor atomic clusters using electron diffraction simulations from atomic models of a metallic glass. Experiments on a Pd 77.5 Cu 6 Si 16.5 metallic glass thin film demonstrate the ability to image the types, sizes, volume fractions, and spatial correlations amongst local rotationally symmetry regions in the glass., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Confabulations are false memories which are expressedwithout the intention to deceive and arise following brain damage or psychological dysfunction. Confabulations can become a barrier to effective neuropsychological rehabilitation and consequently, intervention is required.The current review aimed to provide a detailed evaluative account of existing interventions for confabulation and their relative effectiveness., Method: The search process found 11 studies conducive with the inclusion and exclusion criteria. A methodological quality assessment was then carried out and the majority of included studies demonstrated poor methodological quality., Results: Ten types of interventions were identified and the majority of theseled to a reduction or elimination of confabulations., Conclusion: Since methodological quality of many included studies was deemed unsatisfactory, further large-scale experimental research and standardised measures are necessary to adequately compare the relative effectiveness of these interventions. Further research and clinical implications are also highlighted.

This article presents the design and implementation of a fault tolerant architecture for sensor fusion that tolerates faults on a quadrotor unmanned aerial vehicle (UAV). It aims to tolerate both hardware sensors faults (GPS jamming, IMU lock or freezing, magnetometer sensitivity to high power magnetic fields...) and software faults (faults in the Kalman filter, bad parameters initialization....). The proposed architecture uses data fusion with Kalman filters in order to estimate the states (position and orientation) of the UAV. It includes an analytical redundancy using the dynamic model of the system. The estimations of the defined Kalman filters and the dynamic model feed a weighted average voter, which increases the accuracy of the outputs and the error detection process. The proposed architecture allows multiple recovery solutions to a faulty system and thus increasing its flexibility. The architecture is validated using numerical simulations and experimental flights in real outdoor environment using a quadrotor., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 ISA. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest.

Introduction: Breathing pattern disorders (BPDs) are a common cause of chronic breathlessness, including after acute respiratory illnesses such as COVID pneumonia. BPD is however underdiagnosed, partly as a result of difficulty in clinically assessing breathing pattern. The Breathing Pattern Assessment Tool (BPAT) has been validated for use in diagnosing BPD in patients with asthma but to date has not been validated in other diseases., Methods: Patients undergoing face-to-face review in a post-COVID clinic were assessed by a respiratory physician and specialist respiratory physiotherapist. Assessment included a Dyspnoea-12 (D12) questionnaire to assess breathlessness, physiotherapist assessment of breathing pattern including manual assessment of respiratory motion, and BPAT assessment. The sensitivity and specificity of BPAT for diagnosis of BPD in post-COVID patients was assessed., Results: BPAT had a sensitivity of 89.5% and specificity of 78.3% for diagnosing BPD in post-COVID breathlessness. Patients with a BPAT score above the diagnostic cut-off had higher levels of breathlessness than those with lower BPAT scores (D12 score mean average 19.4 vs 13.2)., Conclusion: BPAT has high sensitivity and moderate specificity for BPD in patients with long COVID. This would support its use as a screening test in clinic, and as a diagnostic tool for large cohort studies., (© Royal College of Physicians 2022. All rights reserved.)

Opioid withdrawal involves the manifestation of motivational and somatic symptoms. However, the brain structures that are involved in the expression of different opioid withdrawal signs remain unclear. We induced opioid dependence by repeatedly injecting escalating heroin doses in male and female C57BL/6J mice. We assessed hyperalgesia during spontaneous heroin withdrawal and somatic signs of withdrawal that was precipitated by the preferential µ-opioid receptor antagonist naloxone. Heroin-treated mice exhibited significantly higher hyperalgesia and somatic signs than saline-treated mice. Following behavioral assessment, we measured regional changes in brain activity by automated the counting of c-Fos expression (a marker of cellular activity). Using Principal Component Analysis, we determined the association between behavior (hyperalgesia and somatic signs of withdrawal) and c-Fos expression in different brain regions. Hyperalgesia was associated with c-Fos expression in the lateral hypothalamus, central nucleus of the amygdala, ventral tegmental area, parabrachial nucleus, dorsal raphe, and locus coeruleus. Somatic withdrawal was associated with c-Fos expression in the paraventricular nucleus of the thalamus, lateral habenula, dorsal raphe, and locus coeruleus. Thus, hyperalgesia and somatic withdrawal signs were each associated with c-Fos expression in unique sets of brain areas. The expression of c-Fos in the dorsal raphe and locus coeruleus was associated with both hyperalgesia and somatic withdrawal. Understanding common neurobiological mechanisms of acute and protracted opioid withdrawal may help identify new targets for treating this salient aspect of opioid use disorder. SIGNIFICANCE STATEMENT The public impact of the opioid crisis has prompted an effort to understand the neurobiological mechanisms of opioid use disorder (OUD). The need to avoid withdrawal symptoms is hypothesized to drive compulsive drug-taking and -seeking in OUD. Thus, understanding the mechanisms of acute and protracted opioid withdrawal may help identify new targets for treating this salient aspect of OUD. We reported brain structures that are associated with the expression of hyperalgesia and somatic signs of opioid withdrawal in male and female heroin-dependent mice. Hyperalgesia during spontaneous opioid withdrawal and somatic withdrawal resulted in c-Fos expression in autonomic and limbic brain regions. The expression of c-Fos in the dorsal raphe and locus coeruleus were associated with both hyperalgesia and somatic withdrawal., Competing Interests: No conflict of interest, (Copyright © 2022 Alvarez-Bagnarol et al.)

Educational strategies globally are changing from an authoritative, top-down model to one focused on greater student and stakeholder participation in planning and implementation of research and educational activities. In addition to emphasis on student-centered education, strategies currently evolve to encompass learning organizations and multistakeholder learning networks. These are essential to address the complexity and scope of tomorrow's challenges, involving issues that could be called 'wicked problems' not easily addressed by single disciplines nor resulting in solutions that please all the players. In this study we describe how a transformative innovation - the NEXTFOOD educational approach - may contribute substantially to a transition of agricultural and food education and how it can be developed and diffused within and between teaching institutions. The method was action research informed by several workshops organized at annual consortium conferences during the first three years of the project. The findings show that a successful transformation involves learning both within and across innovation projects repeated at various organisations in a network. The action research model presented in this paper may be useful as an instrument to support the facilitation of transformative innovations. The transition process resulted in substantial changes in mindset, educational practices and organisational structures at the teaching institutions. However, scaling-up promising educational initiatives may encounter several barriers that need to be overcome at individual, group and institutional levels, and we provide insight on how this can be accomplished in a multi-national consortium of universities., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Melin M et al.)

Intensive agriculture has profoundly altered biodiversity and trophic relationships in agricultural landscapes, leading to the deterioration of many ecosystem services such as pollination or biological control. Information on which spatio-temporal factors are simultaneously affecting crop pests and their natural enemies is required to improve conservation biological control practices. We conducted a study in 80 winter wheat crop fields distributed in three regions of North-western Europe (Brittany, Hauts-de-France and Wallonia), along intra-regional gradients of landscape complexity. Five taxa of major crop pests (aphids and slugs) and natural enemies (spiders, carabids, and parasitoids) were sampled three times a year, for two consecutive years. We analysed the influence of regional (meteorology), landscape (structure in both the years n and n-1) and local factors (hedge or grass strip field boundaries, and distance to boundary) on the abundance and species richness of crop-dwelling organisms, as proxies of the service/disservice they provide. Firstly, there was higher biocontrol potential in areas with mild winter climatic conditions. Secondly, natural enemy communities were less diverse and had lower abundances in landscapes with high crop and wooded continuities (sum of interconnected crop or wood surfaces), contrary to slugs and aphids. Finally, field boundaries with grass strips were more favourable to spiders and carabids than boundaries formed by hedges, while the opposite was found for crop pests, with the latter being less abundant towards the centre of the fields. We also revealed temporal modulation-and sometimes reversion-of the impact of local elements on crop biodiversity. To some extent, these results cause controversy because they show that hedgerows and woodlots should not be the unique cornerstones of agro-ecological landscape design strategies. We point out that combining woody and grassy habitats to take full advantage of the features and ecosystem services they both provide (biological pest control, windbreak effect, soil stabilization) may promote sustainable agricultural ecosystems. It may be possible to both reduce pest pressure and promote natural enemies by accounting for taxa-specific antagonistic responses to multi-scale environmental characteristics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The aim of this review was to assess diagnostic and treatment challenges of adolescents with SI joint pain. We diagnosed 13 of the patients who were referred to our chronic pain clinic because of low back pain (30%) with SI joint pain based on provocative tests response. We performed SI joint steroid infiltration. Six patients (46%) felt better immediately after the procedure and 1 (8%) patient had a one-side only pain relief after a bilateral block. Four of these patients (31%) did not experience any further episode of pain during the follow-up and three patients reported recurring pain on average 2 months after the initial procedure. The 2nd procedure was successful in two patients and the third one experienced pain again 12 months later, requiring a third successful infiltration. Six patients (46%) experienced pain again within a few hours or days after the infiltration and their pain score were unchanged compared with what they had reported prior to the procedure. We were unable to place the needle within the joint under fluoroscopy in 1 patient; however, we were successful repeating the procedure under CT guidance. One patient experienced a motor and sensory block in the distribution of the sciatic nerve immediately after the procedure, which resolved within 24 and 48 hours, respectively. SI joint pain is a distinctive pathology that can be present in children and adolescents and is often overlooked by practitioners. Its diagnosis and management are challenging in this population as it is in adults. SI joint steroids injections may play a role in the management of these patients., (© 2022 The Authors. Paediatric and Neonatal Pain published by John Wiley & Sons Ltd.)

Alternative splicing is frequently involved in the diversification of protein function and can also be modulated for therapeutic purposes. Here we develop a predictive model, called Exon ByPASS (predicting Exon skipping Based on Protein amino acid SequenceS), to assess the criticality of exon inclusion based solely on information contained in the amino acid sequence upstream and downstream of the exon junctions. By focusing on protein sequence, Exon ByPASS predicts exon skipping independent of tissue and species in the absence of any intronic information. We validate model predictions using transcriptomic and proteomic data and show that the model can capture exon skipping in different tissues and species. Additionally, we reveal potential therapeutic opportunities by predicting synthetically skippable exons and neo-junctions arising in cancer cells., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Extracellular vesicles (EVs) have emerged as a promising carrier system for the delivery of therapeutic payloads in multiple disease models, including cancer. However, effective targeting of EVs to cancerous tissue remains a challenge. Here, it is shown that nonviral transfection of myeloid-derived suppressor cells (MDSCs) can be leveraged to drive targeted release of engineered EVs that can modulate transfer and overexpression of therapeutic anticancer genes in tumor cells and tissue. MDSCs are immature immune cells that exhibit enhanced tropism toward tumor tissue and play a role in modulating tumor progression. Current MDSC research has been mostly focused on mitigating immunosuppression in the tumor niche; however, the tumor homing abilities of these cells present untapped potential to deliver EV therapeutics directly to cancerous tissue. In vivo and ex vivo studies with murine models of breast cancer show that nonviral transfection of MDSCs does not hinder their ability to home to cancerous tissue. Moreover, transfected MDSCs can release engineered EVs and mediate antitumoral responses via paracrine signaling, including decreased invasion/metastatic activity and increased apoptosis/necrosis. Altogether, these findings indicate that MDSCs can be a powerful tool for the deployment of EV-based therapeutics to tumor tissue., (© 2021 Wiley-VCH GmbH.)

Purpose of Review: We review and analyze recent literature in public health, urban planning, and disaster management to better understand the relationships between climate change, natural disasters, and root causes of health disparities in the USA., Recent Findings: Existing scholarship establishes clear linkages between climate change and increasing occurrences and severity of natural disasters across the USA. The frequency and types of disasters vary by region and impact both short and long-term health outcomes. Current research highlights health inequities affecting lower income and minoritized communities disproportionately, but data-driven studies critically examining the role of structural inequalities in climate-induced health disparities are sparse. Adding to the body of knowledge, our conceptual framework maps how long-standing structural inequalities in policy, practice, and funding shape vulnerability of lower-income, racially and ethnically marginalized individuals. Vulnerability follows three common pathways: disparities in "exposure", "sensitivity", and "resiliency" before, during, and after a climate disaster. We recommend that future research, policy, and practice shift towards solutions that unearth and address the structural biases that cause environmental disaster and health inequities., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose In this study, we aimed to compare axial length (AL) measurements of the IOLMaster 500 (Carl Zeiss Meditec AG, Jena, Germany), based on partial coherence interferometry (PCI) versus the Aladdin (Topcon Healthcare, Oakland, NJ), based on optical low-coherence interferometry (OLCI), in a clinical setting. Methods A retrospective analysis of the records of patients presenting for cataract surgery at an ophthalmology practice between October 2019 and March 2020 was performed. All patients had biometry measurements on the IOLMaster 500 and the Aladdin. Data collected included patient demographics, cataract morphology and type, and AL measurements. The IOLMaster 500 and Aladdin measurements were compared using the unpaired t-test and Chi-squared test. Results In total, 393 eyes (197 patients) were included (91 males, 107 females) in the study. The IOLMaster 500 was unable to successfully obtain AL measurements in seven eyes (1.8%) and the Aladdin in 26 eyes (6.6%). The difference was statistically significant (p=0.0007). Advanced and central posterior subcapsular cataracts were common in eyes that had unsuccessful measurements. In the eyes successfully measured, the mean AL for the IOLMaster was 24.04 ±1.32 mm, while it was 24.04 ±1.34 mm for the Aladdin. However, this difference was not statistically significant (p=0.9165). Conclusion The IOLMaster 500 performed better in terms of the number of eyes for which AL measurements were successfully obtained compared to the Aladdin. This may be partly related to high volumes of advanced cataracts treated at our practice. However, this being a retrospective study, a cause-and-effect relationship could not be established., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Bhullar et al.)

The goal of this study was to evaluate hepatocyte-specific gene editing, via systemic administration of hyaluronic acid (HA)-based nanoparticles in naïve CD-1 mice. Using HA-poly(ethylene imine) (HA-PEI) and HA-PEI-mannose nanoparticles with differential mannose density (1X and 2X), we have evaluated systemic biodistribution and hepatocyte-specific delivery using IVIS imaging and flow cytometry. Additionally, we have investigated hepatocyte-specific delivery and transfection of CRISPR/Cas9 gene editing plasmid and eGFP gene payload to integrate at the Rosa26 locus. IVIS imaging showed uptake of HA-PEI nanoparticles primarily by the liver, and with addition of mannose at different concentrations, the nanoparticles showed increased uptake in both the liver and spleen. HA-PEI-mannose nanoparticles showed 55-65% uptake by hepatocytes, along with uptake by resident macrophage regardless of the mannose concentration. One of two gRNA targets showed 15% genome editing and obtained similar results for all three nanoparticle formulations. Cells positive for our gene payload were greatest with HA-PEI-mannose-1X nanoparticles where 16.2% of cells were GFP positive. The results were encouraging as proof of concept for the development of a non-viral biodegradable and biocompatible polymeric delivery system for gene editing specifically targeting hepatocytes upon systemic administration., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: This research aims to understand the content and nature, and to explore the harm potential, of suspected 3,4-methylenedioxymethamphetamine (MDMA) substances circulating at music festivals in New South Wales., Methods: Across 19 music festivals held between October 2019 and March 2020, 302 substances detected and suspected by police to contain MDMA were selected for quantitative analysis., Results: Five percent of substances contained a drug other than MDMA (n = 13) or no drug (n = 2). The remaining 95.0% (n = 287) contained MDMA. Of this sub-sample, capsule was the commonest form (83.3%), followed by tablet (7.7%), crystal (6.3%) and powder (2.8%). The median MDMA base-purity of non-tablet forms ranged between 73.5% and 75.0%. The median MDMA base-dose per tablet (116 mg) was higher than per capsule (68 mg). The dose range varied substantially for capsules (14-146 mg) and tablets (24-201 mg). A higher dose (130 mg or greater) was found in 3.5% of MDMA tablets or capsules. Adulterants were identified in 14.1% of MDMA substances but only 1.6% contained a psychoactive adulterant and none presented as dangerous due to their nature or low concentration., Discussion and Conclusions: Dangerous MDMA adulterants or new psychoactive substances in tablet, capsule, powder or crystal forms (whether misrepresented as MDMA or not) were unlikely to be in circulation during the study period. Harm reduction messaging should inform that a key risk-factor for MDMA-related harm is the high and wide variation of purity and dose across forms. Market changes may have occurred since COVID-19, but continued monitoring will ensure messaging remains current., (© 2021 State of New South Wales. Drug and Alcohol Review © 2021 Australasian Professional Society on Alcohol and other Drugs.)