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Decellularized extracellular matrices (dECM) have strong regenerative potential as tissue engineering scaffolds; however, current clinical options for dECM scaffolds are limited to freeze-drying its native form into sheets. Electrospinning is a versatile scaffold fabrication technique that allows control of macro- and microarchitecture. It remains challenging to electrospin dECM, which has led researchers to either blend it with synthetic materials or use enzymatic digestion to fully solubilize the dECM. Both strategies reduce the innate bioactivity of dECM and limit its regenerative potential. Herein, we developed a new suspension electrospinning method to fabricate a pure dECM fibrous mesh that retains its innate bioactivity. Systematic investigation of suspension parameters was used to identify critical rheological properties required to instill “spinnability,” including homogenization, concentration, and particle size. Homogenization enhanced particle interaction to impart the requisite elastic behavior to withstand electrostatic drawing without breaking. A direct correlation between concentration and viscosity was observed that altered fiber morphology; whereas, particle size had minimal impact on suspension properties and fiber morphology. The versatility of this new method was demonstrated by electrospinning dECM with three common decellularization techniques (Abraham, Badylak, Luo) and tissue sources (intestinal submucosa, heart, skin). Bioactivity retention after electrospinning was confirmed using cell proliferation, angiogenesis, and macrophage polarization assays. Collectively, these findings provide a framework for researchers to electrospin dECM for diverse tissue engineering applications.

Background Skeletal muscle dysfunction is common in COPD. Ultrasound-derived rectus femoris cross-sectional area (RFCSA) is a radiation free, non-invasive measure of muscle bulk that relates to quadriceps strength in people with COPD. However, there are limited longitudinal data for RFCSA, and it is not known whether longitudinal change in RFCSA reflects change in quadricep strength, exercise capacity, lower limb function or muscle mass. We aimed to quantify longitudinal change in ultrasound-derived RFCSA and assess its relationship with change in quadriceps maximal voluntary contraction (QMVC), incremental shuttle walk test (ISWT), five-repetition sit-to-stand (5STS) and fat-free mass (FFM) over 12 months in people with COPD. Methods We measured ultrasound-derived RFCSA, QMVC, ISWT, 5STS and FFM (measured by bioelectric impedance analysis) at baseline and 12 months in 169 people with stable COPD. Change was correlated using Pearson's or Spearman's coefficients. Results Baseline characteristics: mean±sd age 70.4±9.4 years; FEV1 53.3±18.9% predicted. Over the course of 12 months mean RFCSA change was −33.7 mm2 (99% CI −62.6– −4.9 mm2; p=0.003) representing a mean±sd percentage change of −1.8±33.5%. There was a weak correlation between change in RFCSA and FFM (r=0.205, p=0.009), but not with change in QMVC, ISWT or 5STS. Conclusion There is a statistically significant decrease in ultrasound-derived RFCSA over 12 months in people with stable COPD, but this decrease does not correlate with change in quadriceps strength, exercise capacity, FFM or lower limb function.

Aims A large body of evidence suggests that experiences of, and access to mental healthcare in England varies according to ethnicity. Inequitable use of restrictive interventions is of particular concern, including within perinatal services: a national-level study of inpatients on Mother and Baby Units (MBU) in 2017 found that 28% of white patients were detained under the mental health act (MHA), compared with 61.5% of Black African, and 66 – 77% of Asian mothers. We carried out an audit with the aim of examining detention rates, length of stay, and time to first section 17 leave on an MBU in South Manchester according to ethnicity and English language ability, to compare with national averages. Methods We identified all patients discharged from Andersen Ward (an MBU) between March 2022 and March 2023. Using electronic medical records we extracted information on: ethnicity, language spoken (English vs other), mental health act status (detained under Section 2/3 vs informal), duration of admission, date of detention, date of first Section 17 leave. We calculated the percentage of patients who were detained according to ethnicity (White British, Mixed/other, Asian, Black), and the odds of detention according to ethnicity. Statistical significance was assessed using chi-squared testing. We also compared average length of stay and time to first section 17 leave by ethnicity. Results 74 patients had been discharged from the MBU within the audit period. 88% of Black inpatients were admitted under the Mental Health act, compared with 72.7% of Asian mothers, 33.3% of Mixed ethnicity or other ethnicities and 28.3% of white mothers. Differences in detention rates according to ethnicity were statistically significant. Of 11 mothers documented as having a language other than English as their primary language, all had been detained. Length of admission and days to first section 17 leave were not significantly different between ethnicities. Conclusion Many factors may contribute to the observed higher detention rates among non-White patients: language barriers and a lack of intercultural competence could lead to risk-averse decision-making during MHA assessments, and different help-seeking patterns might mean White mothers seek help earlier, or for less severe mental health problems. Recommendations include expanding access to high-quality interpreters; investigating factors underlying MHA decision-making through qualitative research; and improving cultural competence among section 12 approved clinicians by incorporating feedback from ethnic minority patients into training and refresher courses.

Amid the SARS-CoV-2 pandemic, concerns surfaced regarding the spread of the virus to wildlife. Switzerland lacked data concerning the exposure of free-ranging animals to SARS-CoV-2 during this period. This study aimed to investigate the potential exposure of Swiss free-ranging wildlife to SARS-CoV-2. From 2020 to 2023, opportunistically collected samples from 712 shot or found dead wild mustelids (64 European stone and pine martens, 13 European badgers, 10 European polecats), canids (449 red foxes, 41 gray wolves, one golden jackal) and felids (56 Eurasian lynx, 18 European wildcats), as well as from 45 captured animals (39 Eurasian lynx, 6 European wildcats) were tested. A multi-step serological approach detecting antibodies to the spike protein receptor binding domain (RBD) and N-terminal S1 subunit followed by surrogate virus neutralization (sVNT) and pseudotype-based virus neutralization assays against different SARS-CoV-2 variants was performed. Additionally, viral RNA loads were quantified in lung tissues and in oronasal, oropharyngeal, and rectal swabs by reverse transcription polymerase chain reactions (RT-qPCRs). Serologically, SARS-CoV-2 exposure was confirmed in 14 free-ranging Swiss red foxes (prevalence 3.1%, 95% CI: 1.9–5.2%), two Eurasian lynx (2.2%, 95% CI: 0.6–7.7%), and one European wildcat (4.2%, 95% CI: 0.2–20.2%). Two positive foxes exhibited neutralization activity against the BA.2 and BA.1 Omicron variants. No active infection (viral RNA) was detected in any animal tested. This is the first report of SARS-CoV-2 antibodies in free-ranging red foxes, Eurasian lynx, and European wildcats worldwide. It confirms the spread of SARS-CoV-2 to free-ranging wildlife in Switzerland but does not provide evidence of reservoir formation. Our results underscore the susceptibility of wildlife populations to SARS-CoV-2 and the importance of understanding diseases in a One Health Concept.

Anthropogenic transmission of SARS-CoV-2 to pet cats highlights the importance of monitoring felids for exposure to circulating variants. We tested cats in the United Kingdom for SARS-CoV-2 antibodies; seroprevalence peaked during September 2021–February 2022. The variant-specific response in cats trailed circulating variants in humans, indicating multiple human-to-cat transmissions over a prolonged period.

When platelet concentrates (PCs) were first introduced in the 1960s as a blood component therapy, they were stored in the cold. As platelet transfusion became more important for the treatment of chemotherapy-induced thrombocytopenia, research into ways to increase supply intensified. During the late 1960s/early 1970s, it was demonstrated through radioactive labeling of platelets that room temperature platelets (RTP) had superior post-transfusion recovery and survival compared with cold-stored platelets (CSP). This led to a universal switch to room temperature storage, despite CSP demonstrating superior hemostatic effectiveness upon being transfused. There has been a global resurgence in studies into CSP over the last two decades, with an increase in the use of PC to treat acute bleeding within hospital and pre-hospital care. CSP demonstrate many benefits over RTP, including longer shelf life, decreased bacterial risk and easier logistics for transport, making PC accessible in areas where they have not previously been, such as the battlefield. In addition, CSP are reported to have greater hemostatic function than RTP and are thus potentially better for the treatment of bleeding. This review describes the history of CSP, the functional and metabolic assays used to assess the platelet storage lesion in PC and the current research, benefits and limitations of CSP. We also discuss whether the application of new technology for studying mitochondrial and glycolytic function in PC could provide enhanced understanding of platelet metabolism during storage and thus contribute to the continued improvements in the manufacturing and storage of PC.

The Special Collection Data Management Planning across Disciplines and Infrastructures of the Data Science Journal consists of papers describing practical experiences, concepts, and future directions on the design and deployment of effective data management plans and associated tools. Papers contain practical examples on managing and sharing data, consider the integration of data management plans into infrastructures and reflect innovative research into new directions for disciplinary and cross-disciplinary data management planning.

Abstract Background The UK is rolling out a national childhood influenza immunisation programme for children, delivered through primary care and schools. Behaviourally-informed letters and reminders have been successful at increasing uptake of other public health interventions. Therefore, we investigated the effects of a behaviourally-informed letter on uptake of the vaccine at GP practices, and of a letter and a reminder (SMS/ email) on uptake at schools. Methods and results Study 1 was a cluster-randomised parallel trial of 21,786 two- and three-year olds in 250 GP practices, conducted during flu season (September to January inclusive) 2016/7. The intervention was a centrally-sent behaviourally-informed invitation letter, control was usual care. The proportion of two- and three-year olds in each practice who received a vaccination by 31st January 2017 was 23.4% in the control group compared to 37.1% in the intervention group (OR = 1.93; 95% CI = 1.82, 2.05, p

Horses and cattle have shown low susceptibility to SARS-CoV-2, and there is no evidence of experimental intraspecies transmission. Nonetheless, seropositive horses in the US and seropositive cattle in Germany and Italy have been reported. The current study investigated the prevalence of antibodies against SARS-CoV-2 in horses and cattle in Switzerland. In total, 1940 serum and plasma samples from 1110 horses and 830 cattle were screened with a species-specific ELISA based on the SARS-CoV-2 receptor-binding domain (RBD) and, in the case of suspect positive results, a surrogate virus neutralization test (sVNT) was used to demonstrate the neutralizing activity of the antibodies. Further confirmation of suspect positive samples was performed using either a pseudotype-based virus neutralization assay (PVNA; horses) or an indirect immunofluorescence test (IFA; cattle). The animals were sampled between February 2020 and December 2022. Additionally, in total, 486 bronchoalveolar lavage (BAL), oropharyngeal, nasal and rectal swab samples from horses and cattle were analyzed for the presence of SARS-CoV-2 RNA via reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Six horses (0.5%; 95% CI: 0.2–1.2%) were suspect positive via RBD-ELISA, and neutralizing antibodies were detected in two of them via confirmatory sVNT and PVNA tests. In the PVNA, the highest titers were measured against the Alpha and Delta SARS-CoV-2 variants. Fifteen cattle (1.8%; 95% CI: 1.0–3.0%) were suspect positive in RBD-ELISA; 3 of them had SARS-CoV-2-specific neutralizing antibodies in sVNT and 4 of the 15 were confirmed to be positive via IFA. All tested samples were RT-qPCR-negative. The results support the hypotheses that the prevalence of SARS-CoV-2 infections in horses and cattle in Switzerland was low up to the end of 2022.

Objective To explore experiences maintaining weight loss 6 months after completing a multicomponent weight loss programme for knee osteoarthritis.Design Qualitative study based on an interpretivist paradigm and a phenomenological approach that was embedded within a randomised controlled trial.Setting Semistructured interviews were conducted with participants 6 months after completing a 6-month weight loss programme (ACTRN12618000930280) involving a ketogenic very low calorie diet (VLCD), exercise and physical activity programme, videoconferencing consultations with a dietitian and physiotherapist, and provision of educational and behaviour change resources and meal replacement products. Interviews were audio recorded, transcribed verbatim and data were analysed based on the principles of reflexive thematic analysis.Participants 20 people with knee osteoarthritis.Results Three themes were developed: (1) successfully maintained weight loss; (2) empowering self-management of weight (understand importance of exercise; increased knowledge about food and nutrition; resources from programme still useful; knee pain as a motivator; confidence in ability to self-regulate weight) and (3) challenges keeping on track (loss of accountability to dietitian and study; old habits and social situations; stressful life events or changes in health).Conclusion Participants had overall positive experiences maintaining their weight loss since completing the weight loss programme and were confident in their ability to self-regulate their weight in the future. Findings suggest a programme incorporating dietitian and physiotherapist consultations, a VLCD, and educational and behaviour change resources supports confidence maintaining weight loss in the medium term. Further research is required to explore strategies to overcome barriers like loss of accountability and returning to old eating habits.

Metastasis is a critical step in the process of carcinogenesis and a vast majority of cancer-related mortalities result from metastatic disease that is resistant to current therapies. Cell migration and invasion are the first steps of the metastasis process, which mainly occurs by two important biological mechanisms, i.e., cytoskeletal remodelling and epithelial to mesenchymal transition (EMT). Akt (also known as protein kinase B) is a central signalling molecule of the PI3K-Akt signalling pathway. Aberrant activation of this pathway has been identified in a wide range of cancers. Several studies have revealed that Akt actively engages with the migratory process in motile cells, including metastatic cancer cells. The downstream signalling mechanism of Akt in cell migration depends upon the tumour type, sites, and intracellular localisation of activated Akt. In this review, we focus on the role of Akt in the regulation of two events that control cell migration and invasion in various cancers including head and neck squamous cell carcinoma (HNSCC) and the status of PI3K-Akt pathway inhibitors in clinical trials in metastatic cancers.

Abstract Background The burden of Parkinson’s disease (PD) worsens with disease progression. However, the lack of objective and uniform disease classification challenges our understanding of the incremental burden in patients with advanced Parkinson’s disease (APD) and suboptimal medication control. The 5–2-1 criteria was proposed by clinical consensus to identify patients with advancing PD. Our objective was to evaluate the screening accuracy and incremental clinical burden, healthcare resource utilization (HCRU), and humanistic burden in PD patients meeting the 5–2-1 screening criteria. Methods Data were drawn from the Adelphi Parkinson’s Disease Specific Program (DSP™), a multi-country point-in-time survey (2017–2020). People with PD who were naive to device-aided therapy and on oral PD therapy were included. Patients meeting the 5–2-1 screening criteria had one or more of the three clinical indicators of APD: (i) ≥5 doses of oral levodopa/day, OR (ii) “off” symptoms for ≥2 h of waking day, OR (iii) ≥1 h of troublesome dyskinesia. Clinician assessment of PD stage was used as the reference in this study. Clinical screening accuracy of the 5–2-1 criteria was assessed using area under the curve and multivariable logistic regression models. Incremental clinical, HCRU, and humanistic burden were assessed by known-group comparisons between 5 and 2-1-positive and negative patients. Results From the analytic sample (n = 4714), 33% of patients met the 5–2-1 screening criteria. Among physician-classified APD patients, 78.6% were 5–2-1 positive. Concordance between clinician judgment and 5–2-1 screening criteria was > 75%. 5–2-1-positive patients were nearly 7-times more likely to be classified as APD by physician judgment. Compared with the 5–2-1-negative group, 5–2-1-positive patients had significantly higher clinical, HCRU, and humanistic burden across all measures. In particular, 5–2-1-positive patients had 3.8-times more falls, 3.6-times higher annual hospitalization rate, and 3.4-times greater dissatisfaction with PD treatment. 5–2-1-positive patients also had significantly lower quality of life and worse caregiver burden. Conclusions 5–2-1 criteria demonstrated potential as a screening tool for identifying people with APD with considerable clinical, humanistic, and HCRU burden. The 5–2-1 screening criteria is an objective and reliable tool that may aid the timely identification and treatment optimization of patients inadequately controlled on oral PD medications.

Objective: To compare the rate of refractive growth (RRG3) of the crystalline lens (“lens”) versus the eye excluding the lens (“globe”) for the fellow, noncataractous eyes of participants in the Infant Aphakia Treatment Study. Design: Retrospective cohort study. Subjects: A total of 114 children who had unilateral cataract surgery as infants were recruited. Biometric and refraction data were obtained from the normal eyes at surgery and at 1, 5, and 10 years. Subjects were included if complete data (axial length [AL], corneal power, and refraction) were available at surgery and at 10 years of age. Methods: At surgery and at 1, 5, and 10 years, AL, corneal power, and cycloplegic refraction were measured in the normal eyes. For each eye, the RRG3 was defined by linear regression of refraction at the intraocular lens (IOL) plane against log10 (age + 0.6 years). The RRG3 for the globe was based on IOL power for emmetropia; the RRG3 for the lens was based on IOL power calculated to give the observed refractions. Intraocular lens powers were calculated with the Holladay 1 formula. The means were compared with a paired 2-tailed t test, and linear regression was used to look for a correlation between RRG3 of the lens globe. Main Outcome Measures: The RRG3 of the lens and globe. Results: Complete data were available for 107 normal eyes. The mean RRG3 of the lenses was −12.0 ± 2.5 diopters (D) and the mean RRG3 of the globes was −14.1 ± 2.7 D (P < 0.001). The RRG3 of the lens correlated with the RRG3 of the globe (R2 = 0.25, P < 0.001). Conclusions: The RRG3 was 2 D more negative in globes compared with lenses in normal eyes. Globes with a greater rate of growth tended to have lenses with a greater rate of growth.

This article rereads Émile Zola’s Le Docteur Pascal (1893) from a critical Medical Humanities perspective to highlight the eponymous doctor’s entanglement with medical practice, thus offering an innovative interpretation of one of Zola’s most maligned novels. Drawing on John Berger’s trope of the country doctor, described in A Fortunate Man: The Story of a Country Doctor (1967), this article foregrounds, firstly, Pascal’s confrontation with his professional inadequacy; and, secondly, the inequality inherent in the doctor- patient relationship. At the same time as demonstrating the value of applying conceptual approaches derived from the critical Medical Humanities to literary studies, my analysis of the doctor-patient relationship in a rural context is of critical interest to the current development of the Medical Humanities.

Abstract We previously reported that growth promoter-induced skeletal muscle hypertrophy co-ordinately upregulated expression of genes associated with an integrated stress response (ISR), as well as potential ISR regulators. We therefore used Adeno-Associated Virus (AAV)-mediated overexpression of these genes, individually or in combination, in mouse skeletal muscle to test whether they induced muscle hypertrophy. AAV of each target gene was injected into mouse Tibialis anterior (TA) and effects on skeletal muscle growth determined 28 days later. Individually, AAV constructs for Arginase-2 (Arg2) and Activating transcription factor-5 (Atf5) reduced hindlimb muscle weights and upregulated expression of genes associated with an ISR. AAV-Atf5 also decreased Myosin heavy chain (MyHC)-IIB mRNA, but increased MyHC-IIA and isocitrate dehydrogenase-2 (Idh2) mRNA, suggesting ATF5 is a novel transcriptional regulator of Idh2. AAV-Atf5 reduced the size of both TA oxidative and glycolytic fibres, without affecting fibre-type proportions, whereas Atf5 combined with Cebpg (CCAAT enhancer binding protein-gamma) only reduced the size of glycolytic fibres and tended to increase the proportion of oxidative fibres. It is likely that persistent Atf5 overexpression maintains activation of the ISR, thereby reducing protein synthesis and/or increasing protein degradation and possibly apoptosis, resulting in inhibition of muscle growth, with overexpression of Arg2 having a similar effect.

Lifestyle factors are known to be influential determinants of health. According to the World Health Organization (WHO), approximately one third of deaths involve unhealthy lifestyle habits. Among lifestyle risk factors for head and neck cancers (HNC), alcohol consumption and smoking have an undeniable role in the multifactorial aetiology of the disease. In recent years, the promotion of healthy lifestyle choices has gained significant attention as contributory to improving health and disease prevention. Interventions to tackle these risk factors are vitally important in disease prevention and progression. However, in order to effectively prevent the disease and reduce the risk factors, it is crucial to identify what upstream reasons lead to the adoption of these lifestyle risk factors in the first place. Stress being a constant aspect of modern-day life is known to contribute to alcohol and smoking practices. In this review paper, relevant literature was searched in PubMed database for stress, lifestyle factors, HNC and cancer to explore the role of stress and its associated biological pathways as an upstream factor in the adoption of lifestyle risk factors that cause HNC. It highlights the importance of stress pathways and the Hypothalamus Pituitary Adrenal (HPA) axis as a locus of interaction between stress, alcohol, smoking and cancer. Despite their widely accepted harmful effects, alcohol and smoking remain deeply rooted in contemporary life. A greater understanding of the impact of stress on lifestyle choices and an exploration of the mechanisms resulting in stress, alcohol- and smoking- related cancer may highlight opportunities for improved prevention measures through the modification of unhealthy lifestyle choices.

Although domestic cats are susceptible to infection with SARS-CoV-2, the role of the virus in causing feline disease is less well defined. We conducted a large-scale study to identify SARS-CoV-2 infections in UK pet cats, using active and passive surveillance. Remnant feline respiratory swab samples, submitted for other pathogen testing between May 2021 and February 2023, were screened using RT-qPCR. In addition, we appealed to veterinarians for swab samples from cats suspected of having clinical SARS-CoV-2 infections. Bespoke testing for SARS-CoV-2 neutralising antibodies was also performed, on request, in suspected cases. One RT-qPCR-positive cat was identified by active surveillance (1/549, 0.18%), during the Delta wave (1/175, 0.57%). Passive surveillance detected one cat infected with the Alpha variant, and two of ten cats tested RT-qPCR-positive during the Delta wave. No cats tested RT-qPCR-positive after the emergence of Omicron BA.1 and its descendants although 374 were tested by active and eleven by passive surveillance. We describe four cases of SARS-CoV-2 infection in pet cats, identified by RT-qPCR and/or serology, that presented with a range of clinical signs, as well as their SARS-CoV-2 genome sequences. These cases demonstrate that, although uncommon in cats, a variety of clinical signs can occur.

Djeya1 (RKLAFRYRRIKELYNSYR) is a very effective cell penetrating peptide (CPP) that mimics the α5 helix of the highly conserved Eya domain (ED) of eyes absent (Eya) proteins. The objective of this study was to bioengineer analogues of Djeya1 that, following effective translocation into planarian tissues, would reduce the ability of neoblasts (totipotent stem cells) and their progeny to regenerate the anterior pole in decapitated S. mediterranea. As a strategy to increase the propensity for helix formation, molecular bioengineering of Djeya1 was achieved by the mono-substitution of the helicogenic aminoisobutyric acid (Aib) at three species-variable sites: 10, 13, and 16. CD analyses indicated that Djeya1 is highly helical, and that Aib-substitution had subtle influences upon the secondary structures of bioengineered analogues. Aib-substituted Djeya1 analogues are highly efficient CPPs, devoid of influence upon cell viability or proliferation. All three peptides increase the migration of PC-3 cells, a prostate cancer line that expresses high concentrations of Eya. Two peptides, [Aib13]Djeya1 and [Aib16]Djeya1, are bioportides which delay planarian head regeneration. As neoblasts are the only cell population capable of division in planaria, these data indicate that bioportide technologies could be utilised to directly manipulate other stem cells in situ, thus negating any requirement for genetic manipulation.

Throughout the COVID-19 pandemic, SARS-CoV-2 infections in domestic cats have caused concern for both animal health and the potential for inter-species transmission. Cats are known to be susceptible to the Omicron variant and its descendants, however, the feline immune response to these variants is not well defined. We aimed to estimate the current seroprevalence of SARS-CoV-2 in UK pet cats, as well as characterise the neutralising antibody response to the Omicron (BA.1) variant. A neutralising seroprevalence of 4.4% and an overall seroprevalence of 13.9% was observed. Both purebred and male cats were found to have the highest levels of seroprevalence, as well as cats aged between two and five years. The Omicron variant was found to have a lower immunogenicity in cats than the B.1, Alpha and Delta variants, which reflects previous reports of immune and vaccine evasion in humans. These results further underline the importance of surveillance of SARS-CoV-2 infections in UK cats as the virus continues to evolve.

A higher prevalence of SARS-CoV-2 infections in animals that have close contact with SARS-CoV-2-positive humans (“COVID-19 households”) has been demonstrated in several countries. This prospective study aimed to determine the SARS-CoV-2 prevalence in animals from Swiss COVID-19 households and to assess the potential risk factors for infection. The study included 226 companion animals (172 cats, 76.1%; 49 dogs, 21.7%; and 5 other animals, 2.2%) from 122 COVID-19 households with 336 human household members (including 230 SARS-CoV-2-positive people). The animals were tested for viral RNA using an RT-qPCR and/or serologically for antibodies and neutralizing activity. Additionally, surface samples from animal fur and beds underwent an RT-qPCR. A questionnaire about hygiene, animal hygiene, and contact intensity was completed by the household members. A total of 49 of the 226 animals (21.7%) from 31 of the 122 households (25.4%) tested positive/questionably positive for SARS-CoV-2, including 37 of the 172 cats (21.5%) and 12 of the 49 dogs (24.5%). The surface samples tested positive significantly more often in households with SARS-CoV-2-positive animals than in households with SARS-CoV-2-negative animals (p = 0.011). Significantly more animals tested positive in the multivariable analysis for households with minors. For cats, a shorter length of outdoor access and a higher frequency of removing droppings from litterboxes were factors that were significantly associated with higher infection rates. The study emphasizes that the behavior of owners and the living conditions of animals can influence the likelihood of a SARS-CoV-2 infection in companion animals. Therefore, it is crucial to monitor the infection transmission and dynamics in animals, as well as to identify the possible risk factors for animals in infected households.

Kv1.3 is a voltage-gated K+-selective channel with roles in immunity, insulin-sensitivity, neuronal excitability and olfaction. Despite being one of the largest ionic conductances of the platelet surface membrane, its contribution to platelet function is poorly understood. Here we show that Kv1.3-deficient platelets display enhanced ADP-evoked platelet aggregation and secretion, and an increased surface expression of platelet integrin αIIb. In contrast, platelet adhesion and thrombus formation in vitro under arterial shear conditions on surfaces coated with collagen were reduced for samples from Kv1.3−/- compared to wild type mice. Use of collagen-mimetic peptides revealed a specific defect in the engagement with α2β1. Kv1.3−/- platelets developed significantly fewer, and shorter, filopodia than wild type platelets during adhesion to collagen fibrils. Kv1.3−/- mice displayed no significant difference in thrombus formation within cremaster muscle arterioles using a laser-induced injury model, thus other pro-thrombotic pathways compensate in vivo for the adhesion defect observed in vitro. This may include the increased platelet counts of Kv1.3−/- mice, due in part to a prolonged lifespan. The ability of Kv1.3 to modulate integrin-dependent platelet adhesion has important implications for understanding its contribution to normal physiological platelet function in addition to its reported roles in auto-immune diseases and thromboinflammatory models of stroke.

Summary: Background: Clonal haematopoiesis driven by mutations in DNMT3A or TET2 has recently been identified as a new risk factor for cardiovascular disease. Experimental studies suggest that these mutations may enhance inflammation which accelerates the disease progression. We aim to investigate the prevalence of mutations in DNMT3A and TET2 and their association with prognosis of patients with ST-segment elevation myocardial infarction (STEMI). Methods: Targeted deep sequencing for DNMT3A and TET2 and inflammatory cytokines (IL-1β, IL-6, TNF-α, INF-γ) were analyzed in 485 patients with STEMI. Major adverse cardiac events (MACE) was a composite of death, myocardial infarction, stroke, or hospitalization due to heart failure. Findings: Patients carrying DNMT3A- or TET2-CH-driver mutations with a variant allele frequency (VAF) ≥2% were found in 12.4% (60 of 485) of STEMI patients and experienced an increased incidence of the death (30.9% vs 15.5%, P = 0.001) and MACE (44.5% vs 21.8%, P

Objectives Type 1 interferon (IFN) is key to the pathogenesis of SLE, evidenced by the expression of IFN-stimulated genes (ISGs) in most patients, but the clinical utility of serial ISG assessment remains unknown. With the emergence of IFN-blocking drugs, we aimed to examine IFN status in relation to clinical findings longitudinally to provide insights into the value of testing ISG levels over time.Methods Clinical data and whole blood were collected prospectively on adult patients with SLE from a single tertiary lupus centre. IFN status was measured using a panel of ISGs.Findings 729 samples were analysed from 205 patients. At baseline, 62.9% of patients were IFN high, 30.2% IFN low and 6.8% borderline. 142 patients had multiple samples collected, and 87.3% of these demonstrated stable ISG status over time. In longitudinal follow-up, IFN high patients had higher activity in multiple organ domains and spent less time in Lupus Low Disease Activity State, but IFN score did not correlate with SLE Disease Activity Index in individual patients. In the small subset of patients who had large fluctuations in ISG across the observation period, most had high-dose glucocorticoids that correlated with ISG suppression. However, low-moderate-dose glucocorticoids did not suppress ISG expression.Conclusion Although IFN high status is associated with indicators of more severe SLE, in the majority of patients, ISGs are stable across time and do not correlate with disease activity. Changes in ISG expression may be seen with high-dose, but not routine dose, glucocorticoid exposure. These findings suggest baseline but not serial ISG measurement may be of value in the management of SLE.

BackgroundCOVID-19, an illness caused by the novel coronavirus SARS-CoV-2, affected many aspects of health care worldwide in 2020. From March to May 2020, New York City experienced a large surge of cases. ObjectiveThe aim of this study is to characterize the prevalence of illness and symptoms experienced by residents and fellows in 2 New York City hospitals during the period of March to May 2020. MethodsAn institutional review board–exempt survey was distributed to emergency medicine housestaff in May 2020, and submissions were accepted through August 2020. ResultsOut of 104 residents and fellows, 64 responded to our survey (a 61.5% response rate). Out of 64 responders, 27 (42%) tested positive for SARS-CoV-2 antibodies. Most residents experienced symptoms that are consistent with COVID-19; however, few received polymerase chain reaction testing. Out of 27 housestaff with SARS-CoV-2 antibodies, 18 (67%) experienced fever and chills, compared with 8 out of 34 housestaff (24%) without SARS-CoV-2 antibodies. Of the 27 housestaff with SARS-CoV-2 antibodies, 19 (70%) experienced loss of taste and smell, compared with 2 out of 34 housestaff (6%) without SARS-CoV-2 antibodies. Both fever and chills and loss of taste and smell were significantly more commonly experienced by antibody-positive compared to antibody-negative housestaff (P=.002 and

In human beings, there are five reported variants of concern of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). However, in contrast to human beings, descriptions of infections of animals with specific variants are still rare. The aim of this study is to systematically investigate SARS-CoV-2 infections in companion animals in close contact with SARS-CoV-2-positive owners (“COVID-19 households”) with a focus on the Delta variant. Samples, obtained from companion animals and their owners were analyzed using a real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and next-generation sequencing (NGS). Animals were also tested for antibodies and neutralizing activity against SARS-CoV-2. Eleven cats and three dogs in nine COVID-19-positive households were RT-qPCR and/or serologically positive for the SARS-CoV-2 Delta variant. For seven animals, the genetic sequence could be determined. The animals were infected by one of the pangolin lineages B.1.617.2, AY.4, AY.43 and AY.129 and between zero and three single-nucleotide polymorphisms (SNPs) were detected between the viral genomes of animals and their owners, indicating within-household transmission between animal and owner and in multi-pet households also between the animals. NGS data identified SNPs that occur at a higher frequency in the viral sequences of companion animals than in viral sequences of humans, as well as SNPs, which were exclusively found in the animals investigated in the current study and not in their owners. In conclusion, our study is the first to describe the SARS-CoV-2 Delta variant transmission to animals in Switzerland and provides the first-ever description of Delta-variant pangolin lineages AY.129 and AY.4 in animals. Our results reinforce the need of a One Health approach in the monitoring of SARS-CoV-2 in animals.

Though most youth in the foster care system aspire to attend college, few have the opportunity to do so. For myriad reasons, including lack of historical representation on college campuses, sub- par Pk-12 education, and postsecondary barriers to admissions, enrollment, and financial aid, most college students who experienced foster care depart college without earning a degree. As the barriers to college for this population of students emerges, postsecondary institutions are preparing their campuses for students with unique needs. This qualitative study explores how student affairs professionals in one university system support college students previously in foster care. Professionals and teams of professionals working at six different institutions across the university system participated in interviews that emphasized the ways campuses used resources to meet students’ hierarchy of needs. Based on the results of this research, student affairs professionals support students’ foundational physiological and safety needs in myriad ways. In doing so, student affair professionals add to the motivation necessary for students to move towards belonging, esteem, and actualization.

This paper presents the application profile for machine-actionable data management plans that allows information from traditional data management plans to be expressed in a machine-actionable way. We describe the methodology and research conducted to define the application profile. We also discuss design decisions made during its development and present systems which have adopted it. The application profile was developed in an open and consensus-driven manner within the DMP Common Standards Working Group of the Research Data Alliance and is its official recommendation.

Background and Objectives: Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide. The relationship between AF and iron deficiency is poorly understood. Materials and Methods: We conducted an observational study investigating the prevalence of iron deficiency in those with AF. Iron deficiency was defined by the American College of Cardiology (ACC) criteria for iron deficiency in heart failure. Results: Of 134 eligible subjects, 81 (60.4%) met the ACC definition of iron deficiency in heart failure. Those who were iron deficient were more likely to be female (OR 1.876, p = 0.005), have a history of diabetes mellitus (OR 3.085, p = 0.001) a history of stroke (OR 3.147, p = 0.016), and have higher CHA2DS2-VASc (p ≤ 0.0001) and Charlson Comorbidity Index scores (CCI) (p = 0.007). Conclusions: The prevalence of iron deficiency in those with AF appears high and warrants evaluation in a prospective study.

The COVID-19 pandemic emerged as a largely unexplained outbreak of pneumonia cases, in Wuhan City, China and rapidly spread across the world. By 11th March 2020, WHO declared it as a global pandemic. The resulting restrictions, to contain its spread, demanded a momentous change in the lifestyle of the general population as well as cancer patients. This augmented negative effects on the mental health of patients with head and neck cancer (HNC), who already battle with the stress of cancer diagnosis and treatment. The causative agent of COVID-19, SARS-CoV2, gains entry through the Angiotensin converting enzyme 2 (ACE2) receptor, which is a component of the Renin Angiotensin System (RAS). RAS has been shown to influence cancer and stress such that it can have progressive and suppressive effects on both. This review provides an overview of SARS-CoV2, looks at how the RAS provides a mechanistic link between stress, cancer and COVID-19 and the probable activation of the RAS axis that increase stress (anxiogenic) and tumor progression (tumorigenic), when ACE2 is hijacked by SARS-CoV2. The mental health crises brought about by this pandemic have been highlighted in many studies. The emerging links between cancer and stress make it more important than ever before to assess the stress burden of cancer patients and expand the strategies for its management.

Abstract Background Hyperspectral imaging is emerging as a promising approach for plant disease identification. The large and possibly redundant information contained in hyperspectral data cubes makes deep learning based identification of plant diseases a natural fit. Here, we deploy a novel 3D deep convolutional neural network (DCNN) that directly assimilates the hyperspectral data. Furthermore, we interrogate the learnt model to produce physiologically meaningful explanations. We focus on an economically important disease, charcoal rot, which is a soil borne fungal disease that affects the yield of soybean crops worldwide. Results Based on hyperspectral imaging of inoculated and mock-inoculated stem images, our 3D DCNN has a classification accuracy of 95.73% and an infected class F1 score of 0.87. Using the concept of a saliency map, we visualize the most sensitive pixel locations, and show that the spatial regions with visible disease symptoms are overwhelmingly chosen by the model for classification. We also find that the most sensitive wavelengths used by the model for classification are in the near infrared region (NIR), which is also the commonly used spectral range for determining the vegetative health of a plant. Conclusion The use of an explainable deep learning model not only provides high accuracy, but also provides physiological insight into model predictions, thus generating confidence in model predictions. These explained predictions lend themselves for eventual use in precision agriculture and research application using automated phenotyping platforms.

Introduction The Coordination of Health Care study was developed by the Australian Institute of Health and Welfare in partnership with the Australian Bureau of Statistics (ABS) to fill an important data gap relating to patient-reported experiences of continuity of care across Australia. Objectives and approach The 2016 Survey of Health Care was administered by the ABS. Over 35,000 responses were weighted to population benchmarks before being linked to administrative datasets including hospital and emergency department care, Medicare Benefits Schedule and Pharmaceutical Benefits Scheme. These linked datasets aim to provide a comprehensive picture of patient journeys in relation to patient-reported experiences of continuity of care. The cross-jurisdictional data linkage spanned state and federal agencies, data linkage units and state health departments. Approvals across 10 different ethics committees were sought. Study management included governance and compliance with state and federal privacy legislation, negotiation of safe transfer of sensitive information across organisations, data interrogation, understanding data quality and study limitations. Specific challenges included sensitivities in response to requested data variables, obtaining private hospital data, understanding state based legislation, particularly in changes to guardianship and consent, working across jurisdictions to meet requirements and communicating linkage protocol. Results All hospital linked datasets were received in early 2020 and currently being validated. Analysis of linked data will investigate continuity themes on low urgency care and potentially preventable hospitalisations. Conclusion Five key lessons learned from the cross-jurisdictional data linkage: • Engage with jurisdictional-based organisations early. Leveraging existing committees in the first instance can help. • Be specific in documentation and approach. • Subtly, every state is different. Local context and state legislation matter. • Governance ethics and compliance take time. Get started early. • Liaise broadly, across and between organisations.

Summary: JQ1 is a BET-bromodomain inhibitor that has immunomodulatory effects. However, the precise molecular mechanism that JQ1 targets to elicit changes in antibody production is not understood. Our results show that JQ1 induces apoptosis, reduces cell proliferation, and as a consequence, inhibits antibody-secreting cell differentiation. ChIP-sequencing reveals a selective displacement of Brd4 in response to acute JQ1 treatment (

This paper explores models, concepts and terminology used in the Research Data Management and Digital Preservation communities. In doing so we identify several overlaps and mutual concerns where the advancements of one professional field can apply to and assist another. By focusing on what unites rather than divides us, and by adopting a more holistic approach we advance towards collective curation and preservation strategies.