bluuebunny/crossref_metadata_2025 huggingface dataset:
O07 Filaggrin insufficiency renders keratinocyte-derived small extracellular vesicles capable of affecting CD1a-mediated T-cell responses and promoting allergic inflammation
Authors: Kobiela Adrian , Hewelt-Belka Weronika , Frąckowiak Joanna E , Kordulewska Natalia , Hovhannisyan Lilit , Bogucka Aleksandra , Etherington Rachel  , Piróg Artur , Dapic Irena  , Gabrielsson Susanne , Brown Sara , Ogg Graham S   , Gutowska-Owsiak Danuta
Published: July 2023

The association between FLG loss-of-function mutations and the development of atopic dermatitis (AD) indicates that filaggrin is critical to skin barrier function; the mutations are also linked to additional allergic manifestations, but it is unknown how the skin may influence inflammation in distant tissues. Here we investigated the impact of filaggrin insufficiency on keratinocyte-derived exosome-enriched small extracellular vesicles (sEVs) and found that those secreted by filaggrin-knockdown cells are extensively remodelled as a consequence of the abnormal keratinocyte differentiation process. The altered sEV lipidome changes the sEV capacity to promote T-cell responses by direct effect on self-lipid neoantigen generation, modulating the content of permissive (stimulatory) and nonpermissive (inhibitory) CD1a ligands released from the sEV membranes by phospholipase A2. Presentation of those lipids to T cells results in the redirection from a type 1 to a type 2 response. We found that the aberrant sEV lipid composition mirrors a generalized remodelling of cellular lipids resulting from dysregulated expression of multiple enzymes of lipid metabolic pathways, observed both in filaggrin knockdown keratinocytes in vitro and in the skin of patients with AD. Hence, filaggrin insufficiency background renders keratinocytes capable of supplying CD1a ligands which are capable of impeding both homeostasis-promoting and protective antimicrobial responses, enhancing type 2 T-cell activation to perpetuate inflammation in AD skin. sEV transfer by systemic circulation may promote similar effects in distant tissues.
O14 Junctional epidermolysis bullosa: repairing the epidermal lipid barrier
Authors: Jones Eleri , Marsh Supatra , O'Shaughnessy Ryan , Aumailley Monique , McGrath John  , O’Toole Edel  , Caley Matthew
Published: July 2023

Junctional epidermolysis bullosa (JEB) caused by loss of function mutations in basement membrane genes, including that encoding laminin-332, is among the most severe forms of epidermolysis bullosa. Affected individuals suffer from blistering from birth, leading to scarring, granulation tissue and susceptibility to infection. In generalized severe JEB, there is a 50% mortality rate in the first 2 years of life, often due to failure to thrive or overwhelming infection. Using cells with knockdown of laminin-α3 we generated a RNAseq data set and have identified a new pathway altered in JEB, the regulation of cholesterol biosynthesis. It has been shown that loss of laminin-332 results in reduced epidermal lipid barrier specifically due to loss of cholesterol transport within keratinocytes. Cholesterol biosynthesis and cholesterol trafficking are fundamental processes in a wide range of cells and tissues, especially in the formation of the normal epidermal lipid barrier. A cholesterol transport screening assay has been developed and used to analyse the ability of 10 specifically selected compounds to restore cholesterol transport in our in vitro model of JEB. Results of this small-scale screen showed that nine of 10 of the selected drugs were able to restore cholesterol transport up to 50% of control. Six drugs were selected for further analysis within our three-dimensional (3D) skin-equivalent model of JEB. Organotypic skin equivalents of normal skin (siControl) and JEB skin (siLaminin-α3) were treated daily for 7 days with either dimethyl sulfoxide or 1 µmol L–1 of selected drugs. In 3D, drugs 1, 3, 5 and 6 displayed an increase in stratum corneum lipids shown by Nile red staining. Drugs 4 and 7 did not increase stratum corneum lipids above levels seen in the untreated JEB organotypics. Further analysis of skin differentiation by keratin, involucrin and tranglutaminase staining were assessed to narrow drug selection for further testing. These data also suggest that JEB is not just a disorder of epidermal–dermal adhesion, but a disorder of aberrant cholesterol trafficking causing a markedly impaired skin barrier. These findings suggests that drugs to target cholesterol transport within keratinocytes could be a beneficial treatment for JEB, helping to improve the crucial epidermal lipid barrier and prevent water loss and infection at the early stages of life.
O18 Molecular crosstalk between PLCγ1 and STAT3 in cutaneous T-cell lymphoma
Authors: Campbell Victoria , Flanagan Charlotte , Tosi Isabella  , Jones Christine , Whittaker Sean , John Susan , Mitchell Tracey
Published: July 2023

Cutaneous T-cell lymphoma (CTCL) is a non-Hodgkin lymphoma of skin-homing T lymphocytes that is difficult to diagnose and treat due to a high degree of clinical and genomic heterogeneity. Mutations in PLCG1/PLCγ1 occur in 10% of CTCL tumours. Meanwhile, signal transducer and activator of transcription 3 (STAT3) – a common driver of lymphomagenesis – is frequently activated (pY705-STAT3) in CTCL in the absence of mutation. Activation of STAT3 may also be mediated by serine phosphorylation (pS727-STAT3), and there is a lack of data on the role of this modification in CTCL. We aimed to identify if gain-of-function PLCG1 mutations in CTCL activate STAT3, either directly or indirectly, via downstream mitogen-activated protein kinase (MAPK) signalling. Flow cytometry was used to study STAT3 phosphorylation and subcellular localization in ex vivo CD4+-enriched tumour cell populations from patients with CTCL and healthy donors. STAT3 phosphorylation was also studied in the J.gamma1 T-cell line (PLCγ1-null) and primary ex vivo CD4+ cells upon lentiviral overexpression of wild-type (WT) and mutant (p.R48W, p.S345F) PLCγ1 constructs. To investigate the role of MAPK signalling, the CTCL-derived Hut78 and SeAx cell lines were treated with MAPK inhibitors (trametinib), and STAT3 phosphorylation assessed by Western blotting. Significantly increased basal levels of pS727-STAT3 (P < 0.05) and pY705-STAT3 (P < 0.001) were observed in CD4+-enriched populations from patients with Sézary syndrome compared with healthy donors. Mitochondrial translocation of STAT3 was also increased in CD4+-enriched populations from patients with Sézary syndrome (P < 0.05). In transduced J.gamma1 cells, p.S345F-PLCγ1 overexpression activated pS727-STAT3 (P < 0.05), while overexpression of both WT and mutant PLCγ1 constructs activated pS727-STAT3 in primary ex vivo CD4+ cells (P < 0.05 and P < 0.01, respectively). Inhibition of MAPK kinase (MEK)–extracellular signal regulated kinase (ERK) signalling did not significantly modulate STAT3 phosphorylation or subcellular localization in CTCL cell lines, suggesting that pS727-STAT3 phosphorylation is not mediated via ERK in CTCL. This work extends our understanding of PLCγ1 signalling and identifies pS727-STAT3 as a potential target of interest for further study in CTCL.
PostersP01 Tissue slice culture as a patient-derived explant model to investigate immunity and immunotherapy in cutaneous squamous cell carcinoma
Authors: Coltart George , Lai Chester , Al-Shamkhani Aymen , Healy Eugene
Published: July 2023

Cutaneous squamous cell carcinoma (cSCC) is one of the commonest cancers worldwide with the capacity to metastasize. Immune evasion by the tumour prevents its elimination and allows it to progress, including enabling the cancer to spread to local lymph nodes and distant organs. Targeting this dysfunctional immunity is a key strategy for the treatment of cSCC and anti-PD-1 checkpoint inhibition is now the first-line therapy for advanced and metastatic cSCC. However, complete responses to anti-PD-1 are seen in < 15% of patients and therefore it is vital that other strategies for enhancing anticancer immunity in cSCC are explored. Given the expense of clinical trials, it is essential to have good preclinical data to target cancer drug development appropriately, and this can be challenging in the investigation of cancer immunotherapy, as these treatments rely upon an intact human immune–tumour interface. We have developed a tumour slice culture (TSC) system to investigate the mechanism and efficacy of immune-modulating anticancer therapy in cSCC. This patient-derived explant model involves taking tissue slices from freshly excised tumours and culturing the slices under different experimental conditions, while maintaining the tumour microarchitecture of each slice. We cultured > 50 tumours using the TSC platform, including 35 cSCCs. Immunofluorescent confocal microscopy of anti-CD4 demonstrates penetration of antibody throughout the tissue slice. The mean (SD) viability of lymphocytes (T and B cells) determined by flow cytometry after 72 h of culture was 90.3% (7.89%; n = 31). Treatment of slices with OKT3 anti-CD3 antibody for 72 h induces a dose–response increase in T-cell Ki67 expression (2.87% unstimulated vs. 13% OKT3 100 ng mL–1; P < 0.001) and CD8+ T-cell granzyme B (47.6% unstimulated vs. 63.7% OKT3 ng mL–1; P = 0.064), as detected by flow cytometry (n = 7). Enzyme-linked immunosorbent assay of the culture supernatant showed that interferon-γ concentrations increased from <9.6 pg mL–1 (unstimulated) to 131.1 pg mL–1 [OKT3 1000 ng mL–1 (n = 6, P < 0.05]. To our knowledge the TSC system has not previously been used in cSCC and represents a promising technique to investigate new potential immunotherapies in this cancer.
P10 Inducible 14-3-3 sigma/stratifin ablation cooperates with rasHa activation to accelerate papillomatogenesis and induce malignant conversion in transgenic mouse skin carcinogenesis
Authors: Hardman-Carter Rebecca , Lefkati Revvekka , McMenemy Carol  , Greenhalgh David
Published: July 2023

In carcinogenesis, the 14-3-3σ isoform (stratifin) is implicated by being downregulated in a mode of classic tumour suppression gene (TSG) loss and also via elevated oncogenic roles; with both scenarios appearing to be hallmarks of 14-3-3σ deregulation, depending on tumour stage or context. Mouse skin models highlight tumour-suppressive roles, as the Er/Er+/– repeated epilation stain possesses germline mutations that result in hyperplasia, failed follicular differentiation and susceptibility to squamous cell carcinoma (SCC). In transgenic models, 14-3-3σ knockout supports early roles, resulting in rapid papilloma formation in classic two-stage DMBA/TPA chemical carcinogenesis; however, our previous studies in this model demonstrated targeted overexpression of 14-3-3σ led to SCC of a follicular origin in collaboration with Fos and well-differentiated SCC in collaboration with rasHa. Therefore, to study mechanisms driving/inhibiting skin carcinogenesis, stage-specific expression of endogenous 14-3-3σ (stratifin) was analysed in early skin carcinogenesis driven by activated rasHa expression (HK1.ras) and subsequently via conditional RU486-inducible 14-3-3σ knockout (K14.creP-Δ14-3-3σ). Consistent with 14-3-3σ roles previously observed in epidermal differentiation, HK1.ras hyperplasia and early papillomas displayed elevated 14-3-3σ expression in suprabasal keratinocytes and in occasional K1-positive basal keratinocytes as they committed to differentiate. Older HK1.ras mice exhibited increasing 14-3-3σ positivity in papilloma basal layers, suggesting attempts to protect basal-layer p53 TSG function, given that 14-3-3σ acts as a chaperone protein to remove/relocate MDM2 for degradation, thus maintaining p53 levels. Indeed, such papillomas expressed activated p-MDM2166 confined to suprabasal layers, resulting in strong basal layer p53 expression and thus HK1.ras papillomas lacked malignant conversion. In mice where 14-3-3σ functions were ablated via an RU486-inducible Cre/loxP system expressed from a keratin 14 (K14) promoter (K14.creP-Δ14-3-3σ), treated HK1.ras-K14.Δ14-3-3σ mice exhibited a rapid papillomatogenesis and produced larger papillomas. These papillomas also exhibited rapid conversion to malignancy, associated with increased activated p-MDM2166 expression in basal layers and resultant p53 loss. These observations suggest that 14-3-3σ plays tumour suppressive roles involving p53 protection, where failure to regulate MDM2 activity led to p53 loss and susceptibility to malignant conversion.

P11 Abstract withdrawn.
P12 Tetrapeptide matrikines synchronize circadian rhythms and promote proliferation in human skin cells
Authors: El-Houni Zeyad , Eckersley Alexander , Bell Mike , Bradley Eleanor , Newton Victoria , Sherratt Michael  , Meng Qing Jun
Published: July 2023

Circadian rhythms are intrinsically generated 24 h rhythms that play a vital role in enabling the skin to adapt temporally to various external stimuli. These include ultraviolet radiation, physical trauma and water loss. At the molecular level, circadian clocks consist of various clock genes and proteins, including Per2/Cry1 and Bmal1/Clock, forming autoregulatory feedback loops. Although these rhythms are known to be impaired in ageing skin, there are limited therapeutic options to restore skin cell circadian function. As small peptides with homology to amino acid sequences found in extracellular matrix proteins (matrikines) can beneficially affect clinical and histological markers of skin ageing, in this study we characterized the ability of two novel tetrapeptides to influence the cellular circadian clocks of skin cells. HaCat keratinocytes transduced with a human Per2::luc promoter-driven reporter were used to monitor the effects of two synthetically generated peptides, GPKG and LSVD, on the cells’ intrinsic circadian clock. Following administration of these peptides at various concentrations (4–16 ppm), the oscillatory activity of the cells was amplified up to twofold vs. the vehicle control. LSVD was found to induce Per2::luc promoter activity significantly (P < 0.05). In addition to enhancing circadian rhythmicity, both peptides were assessed for their proliferative effect (by Incucyte imaging and MTT cell proliferation assays). At the higher concentrations tested, both GPKG and LSVD significantly increased proliferation in HaCat keratinocytes (P < 0.05). In conclusion, these peptides have been found to be highly effective in synchronizing the circadian clock in skin cells, leading to changes in their behaviour. This implies that these new peptides may have beneficial effects on skin cells, in part, by improving their circadian function. Given the findings of clock disruption in a number of diseases, as well as with age, identifying compounds that can reset the clock in skin cells is an important approach to developing treatments that can improve the functioning of cutaneous physiological processes that are under circadian control.

Funding sources: this study was funded by the No. 7 Beauty Company.
P17 A signature of IL-36 activation in systemic lupus erythematosus skin
Authors: Sumner Emma J , McCluskey Daniel , Mahil Satveer K   , Lewis Myles , Capon Francesca 
Published: July 2023

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with heterogeneous presentation. Joint and kidney disease represent the largest cause of morbidity, and visually distinctive skin complications are often present. While it has long been established that organ damage is caused by autoantibodies forming large immune complexes in the affected tissues, a detailed understanding of disease processes is still lacking. Here, we propose that interleukin (IL)-36 cytokines, which drive cutaneous and systemic symptoms in psoriasis, are also implicated in the pathogenesis of SLE. Given that the IL-36 receptor is prominently expressed in keratinocytes, we investigated this hypothesis in skin. We first carried out a systematic review of SLE single-cell RNA sequencing studies, identifying two data sets (∼50 000 cells in total) generated from patient skin biopsies. We processed both data sets with the same standardized pipeline, using the Seurat package. This identified 10 distinct cell clusters, replicating the cell types described in the original studies and identifying the main cell populations observed in human skin. Subsequent gene expression analysis confirmed that, in both data sets, the expression of IL36G and IL1RL2 (the genes encoding IL-36γ and its receptor) was highest in keratinocytes. Interestingly, subclustering showed that this signal was driven by the expression of IL36G in supraspinous keratinocytes and of IL1RL2 in proliferating keratinocytes. In the first data set, the expression of IL36G and IL1RL2 was readily detectable in lesional keratinocytes but virtually nonexistent in their nonlesional counterparts. A comparison of lesional and nonlesional keratinocytes also identified 297 differentially expressed genes (DEGs; log2 fold change > 1.2, false discovery rate < 0.05) in the first study and 234 in the second. To further explore these findings, we compared the above DEG with a set of 182 genes (previously defined by our group) that are upregulated in IL-36-stimulated keratinocytes. This demonstrated a significant over-representation of the IL-36 signature genes among the DEGs observed in lesional SLE keratinocytes (P < 0.005 in both data sets). These observations indicate that IL-36 is likely to contribute to skin inflammation in SLE, warranting further studies of this cytokine in organs affected by the disease.
P21 Tyrosine and serine STAT3 phosphorylation drives cutaneous squamous cell carcinoma in recessive dystrophic epidermolysis bullosa as demonstrated using a 3D in vitro model
Authors: Llopis-Hernandez Virginia , Balon Katarzyna , Chen Dawei , Mellerio Jemima , McGrath John , Jacków Joanna
Published: July 2023

The early onset of aggressive cutaneous squamous cell carcinoma (cSCC) and its rapid progression in recessive dystrophic epidermolysis bullosa (RDEB) leads to nearly 100% mortality rates in these patients. Elevated levels of phospho-STAT3 on tyrosine residue (STAT3Tyr705) have been intensively demonstrated in RDEB-derived cSCC cells, demonstrating that the constitutive activation and dysregulation of the Janus kinase (JAK)/STAT pathway plays a role in RDEB cSCC pathogenesis. We efficiently applied ruxolitinib (JAK1/2 inhibitor that blocks phosphorylation on STAT3Tyr705) to a RDEB–cSCC xenograph mouse model, reducing the size of small tumours but found that it was insufficient to reduce bigger tumours completely. Recently, phosphorylation at serine-727 (STAT3Ser727) has been shown to be relevant in the evolution of some cancers, but it has not yet been studied in RDEB cSCC. We hypothesized that phosphorylation at serine-727 of the STAT3 pathway might play a role in RDEB cSCC tumour development and progression, and could not be inhibited by ruxolitinib. To validate our hypothesis, we studied two RDEB cSCC human patient samples with different degrees of dedifferentiation (normal RDEB skin, edge of the tumour and centre of the RDEB cSCC). We demonstrated that STAT3Tyr705 was preferentially upregulated in the normal RDEB skin followed by the tumour edge skin, presenting less phosphorylation on the tumour. When we analysed STAT3 phosphorylation on STAT3Ser727, we could see that it presented the opposite phosphorylation pattern, being more phosphorylated in the tumour and less in normal RDEB skin. Furthermore, we validated the STAT3Ser727residue pattern across other cSCC cell lines and found that serine phosphorylation is present in other SCCs, demonstrating its crucial role in tumour development. To further investigate and analyse cancer progression in more detail, an easy and robust RDEB cSCC model is instrumental. Therefore, we generated RDEB cSCC spheroids in vitro, which has four key advantages over the previous models developed: (i) it is easy to generate; (ii) small amounts of cells are required; (iii) it is suitable for drug testing; and (iv) it can be used to recapitulate different stages of tumour development. We have been able to control their size and use them for drug testing, observing a 20% size decrease after 6 days of ruxolitinib treatment. Taken together, this three-dimensional RDEB cSCC in vitro model, along with analysis of human samples, will allow us to better understand RDEB cSCC progression at different stages, allowing us to investigate new treatments for RDEB cSCC.
Ontological (In)security in Early Career Social Work during COVID-19: Experiences in Scotland
Authors: Sen Robin , Daly Maura , McCulloch Trish , Grant Scott , Clarke David , Ferrier Claire
Published: July 2023

The impact of COVID-19 on the working lives of professionals has been of much interest. Within social work, the pandemic increased workload demands, whilst the way in which work was done shifted significantly. This article uses data gathered from newly qualified social workers (NQSWs) who began their working lives during the pandemic. These first years in practice are viewed as an extension to social workers’ formal education and as a vital stage in their professional development. Survey (n = 124) and interview (n = 12) data were gathered from NQSWs across Scotland. Findings were considered through Giddens’ lens of ontological security, to explore NQSW transitions during a context of pandemic disruption and its impacts on NQSWs’ confidence and competence, as well as their sense of self and identity. Consistent with other studies, respondents were most impacted by home working and the associated isolation and separation from colleagues, particularly when engaged in emotionally charged work. Findings uncovered a trichotomy of experience, with variation in the quality and availability of some formal supports—induction, training and learning and development—and informal support. Implications for practice include a need to focus on how we support and nurture NQSWs at such a critical stage in their professional socialisation.
Sitosterolaemia presenting with consistent skin xanthomas in a pair of monozygotic twins who responded to ezetimibe treatment
Authors: Zhong Zemin , Yang Chao , Lin Zhimiao
Published: July 2023

We described for the first time, to the best of our knowledge, sitosterolaemia in monozygotic twins. They presented with almost identical skin xanthomas that responded well to treatment. Raising awareness of sitosterolaemia is crucial, as early diagnosis and treatment are imperative to prevent the associated risk of atherosclerotic heart disease.
Velocity of conduction between columns and layers in barrel cortex reported by parvalbumin interneurons
Authors: Scheuer Katherine S , Judge John M , Zhao Xinyu , Jackson Meyer B
Published: July 2023

Inhibitory interneurons expressing parvalbumin (PV) play critical roles throughout the brain. Their rapid spiking enables them to control circuit dynamics on a millisecond time scale, and the timing of their activation by different excitatory pathways is critical to these functions. We used a genetically encoded hybrid voltage sensor to image PV interneuron voltage changes with sub-millisecond precision in primary somatosensory barrel cortex (BC) of adult mice. Electrical stimulation evoked depolarizations with a latency that increased with distance from the stimulating electrode, allowing us to determine conduction velocity. Spread of responses between cortical layers yielded an interlaminar conduction velocity and spread within layers yielded intralaminar conduction velocities in different layers. Velocities ranged from 74 to 473 μm/ms depending on trajectory; interlaminar conduction was 71% faster than intralaminar conduction. Thus, computations within columns are more rapid than between columns. The BC integrates thalamic and intracortical input for functions such as texture discrimination and sensory tuning. Timing differences between intra- and interlaminar PV interneuron activation could impact these functions. Imaging of voltage in PV interneurons reveals differences in signaling dynamics within cortical circuitry. This approach offers a unique opportunity to investigate conduction in populations of axons based on their targeting specificity.
EEG functional connectivity after perinatal stroke
Authors: Kavčič Alja , Demšar Jure , Georgiev Dejan , Meglič Nuška Pečarič , Šalamon Aneta Soltirovska
Published: July 2023

Impaired cognitive functioning after perinatal stroke has been associated with long-term functional brain network changes. We explored brain functional connectivity using a 64-channel resting-state electroencephalogram in 12 participants, aged 5–14 years with a history of unilateral perinatal arterial ischemic or haemorrhagic stroke. A control group of 16 neurologically healthy subjects was also included—each test subject was compared with multiple control subjects, matched by sex and age. Functional connectomes from the alpha frequency band were calculated for each subject and the differences in network graph metrics between the 2 groups were analyzed. Our results suggest that the functional brain networks of children with perinatal stroke show evidence of disruption even years after the insult and that the scale of changes appears to be influenced by the lesion volume. The networks remain more segregated and show a higher synchronization at both whole-brain and intrahemispheric level. Total interhemispheric strength was higher in children with perinatal stroke compared with healthy controls.
Association between dietary vitamin E intake and chronic kidney disease events in US adults: a cross-sectional study from NHANES 2009–2016
Authors: Li Jiyuan , Liu Ziyi , Pu Yan , Dai Helong , Peng Fenghua
Published: July 2023

Background

The relationship between vitamin E supplementation and the prevalence of chronic kidney disease (CKD) is unclear. We discussed the relationship between vitamin E intake and CKD prevalence and further investigated the effect on different CKD risk strata.

Methods

We ultimately included 20 295 participants from the National Health and Nutrition Examination Survey (NHANES) database from 2009 to 2016. Multiple logistic regression and restricted cubic splines (RCS) were applied to explore the relationship between vitamin E intake and CKD prevalence and risk stratification. Subgroup analysis was applied to assess the stability of the association between vitamin E intake and CKD.

Results

In the CKD prevalence study, we found a negative association between high vitamin E intake and CKD prevalence through an adjusted multiple logistic regression model, the odds ratio (OR) was 0.86 [95% confidence interval (CI) 0.74–1.00; P for trend = .041] and RCS showed a nonlinear negative correlation (P-nonlinear = .0002, <.05). In the CKD risk stratification study, we found that in very high–risk patients, the OR was 0.51 (95% CI 0.32–0.84; P for trend = .006) and the RCS also showed a nonlinear negative correlation (P-nonlinear <.0001, <.05). Subgroup analysis demonstrated that the correlations were stable across populations (P-values >.01 for all interactions).

Conclusion

Dietary vitamin E intake was negatively associated with the prevalence of CKD in US adults. Increased vitamin E intake was a protective factor across CKD risk strata, and as vitamin E intake increased, there was a non-linear downward trend in the proportion progressing to very high–risk CKD.
Habitat and vertical stratification affect capture of stink bugs (Hemiptera: Pentatomidae) and biological control of the invasive brown marmorated stink bug
Authors: Cottrell Ted E , Tillman Glynn , Grabarczyk Erin E , Toews Michael , Sial Ashfaq , Lahiri Sriyanka
Published: July 2023

Spatiotemporal distribution of stink bugs (Hemiptera: Pentatomidae) and their natural enemies across farmscapes has been studied in more detail recently. However, the impact of plant height on vertical stratification of stink bugs and their natural enemies is rarely addressed across these diverse habitats. In this study, we examined capture of native stink bugs, the invasive brown marmorated stink bug, Halyomorpha halys (Stål)(Hemiptera:Pentatomidae), and a predaceous wasp, Astata occidentalis Cresson (Hymenoptera: Sphecidae) in pheromone-baited traps, in 2 habitats, woodlands of mostly deciduous trees mixed with some conifers and pecan orchards, in addition to their vertical stratification (0–13.7 m) at increasing heights. Furthermore, the effects of canopy height and habitat on H. halys egg mass predation and parasitism were evaluated. Adult H. halys were abundant in both habitats, but more nymphs were captured in pecan orchards. The same pattern was found for adult Euschistus servus (Say) (Hemiptera:Pentatomidae), Thyanta custator McAtee (Hemiptera:Pentatomidae), and A. occidentalis. In contrast, adult E. tristigmus (Say) (Hemiptera:Pentatomidae) and Chinavia hilaris (Say) (Hemiptera:Pentatomidae) were more abundant in woodlands. More nymphal H. halys and adults of E. servus, T. custator, and A. occidentalis were captured in ground traps than canopy traps in pecan. More adult and nymphal H. halys were captured at varying heights in the woodland canopy compared to near the ground as were adult E. tristigmus and C. hilaris. Both parasitism and predation occurred in woodland and pecan canopies. However, in one test we found that parasitism of H. halys egg masses occurred more often in the upper tree canopy, and more parasitism was detected in woodland than orchard habitat. In 2 tests, predation was higher in woodlands than pecan orchards. These results will aid in optimizing conservation biological control tactics in these habitats.
Changes in pulmonary function in lung cancer patients after segmentectomy or lobectomy: a retrospective, non-intervention, observation study
Authors: Bao Minwei , Lang Zhongping , Wang Zhuofu , Zhang Xuhong , Zhao Long
Published: July 2023

OBJECTIVES

Pulmonary segmentectomy (SE) became an increasingly popular method for resection of early-stage lung cancer. This study aims to compare the impact of single SE (SSE), multiple SE (MSE) and lobectomy (LE) on postoperative pulmonary function in patients with NSCLC.

METHODS

Medical records of a total of 1284 patients who underwent LE (n = 493), SSE (n = 558) and MSE (n = 233) at Shanghai Pulmonary Hospital from January 2013 to October, 2020 were retrospectively analysed. Pulmonary function tests (PFTs) were performed preoperatively and 12 months after surgery.

RESULTS

SSE was associated with a significantly smaller decline in the PFT values compared to MSE and LE. There was a poor consistency between the observed and expected (O/E) loss of pulmonary function in all study groups (P < 0.05). Both LE and SE resulted in similar O/E ratios of all PFT parameters (P > 0.05).

CONCLUSIONS

Overall loss of pulmonary function was much greater after LE than after both SSE and MSE. MSE was associated with higher postoperative pulmonary function decline compared to SSE but was still beneficial over LE. Both LE and SE groups had similar PFT loss per segment (P > 0.05).
Diet, cardiovascular disease, and mortality in 80 countries
Authors: Mente Andrew , Dehghan Mahshid , Rangarajan Sumathy , O’Donnell Martin , Hu Weihong , Dagenais Gilles , Wielgosz Andreas , A. Lear Scott , Wei Li , Diaz Rafael , Avezum Alvaro , Lopez-Jaramillo Patricio , Lanas Fernando , Swaminathan Sumathi , Kaur Manmeet , Vijayakumar K , Mohan Viswanathan , Gupta Rajeev , Szuba Andrzej , Iqbal Romaina , Yusuf Rita , Mohammadifard Noushin , Khatib Rasha , Nasir Nafiza Mat , Karsidag Kubilay , Rosengren Annika , Yusufali Afzalhussein , Wentzel-Viljoen Edelweiss , Chifamba Jephat , Dans Antonio , Alhabib Khalid F , Yeates Karen , Teo Koon , Gerstein Hertzel C , Yusuf Salim
Published: July 2023

Aims

To develop a healthy diet score that is associated with health outcomes and is globally applicable using data from the Prospective Urban Rural Epidemiology (PURE) study and replicate it in five independent studies on a total of 245 000 people from 80 countries.

Methods and results

A healthy diet score was developed in 147 642 people from the general population, from 21 countries in the PURE study, and the consistency of the associations of the score with events was examined in five large independent studies from 70 countries. The healthy diet score was developed based on six foods each of which has been associated with a significantly lower risk of mortality [i.e. fruit, vegetables, nuts, legumes, fish, and dairy (mainly whole-fat); range of scores, 0–6]. The main outcome measures were all-cause mortality and major cardiovascular events [cardiovascular disease (CVD)]. During a median follow-up of 9.3 years in PURE, compared with a diet score of ≤1 points, a diet score of ≥5 points was associated with a lower risk of mortality [hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.63–0.77)], CVD (HR 0.82; 0.75–0.91), myocardial infarction (HR 0.86; 0.75–0.99), and stroke (HR 0.81; 0.71–0.93). In three independent studies in vascular patients, similar results were found, with a higher diet score being associated with lower mortality (HR 0.73; 0.66–0.81), CVD (HR 0.79; 0.72–0.87), myocardial infarction (HR 0.85; 0.71–0.99), and a non-statistically significant lower risk of stroke (HR 0.87; 0.73–1.03). Additionally, in two case-control studies, a higher diet score was associated with lower first myocardial infarction [odds ratio (OR) 0.72; 0.65–0.80] and stroke (OR 0.57; 0.50–0.65). A higher diet score was associated with a significantly lower risk of death or CVD in regions with lower than with higher gross national incomes (P for heterogeneity <0.0001). The PURE score showed slightly stronger associations with death or CVD than several other common diet scores (P < 0.001 for each comparison).

Conclusion

A diet comprised of higher amounts of fruit, vegetables, nuts, legumes, fish, and whole-fat dairy is associated with lower CVD and mortality in all world regions, especially in countries with lower income where consumption of these foods is low.
Very-early symptomatic recurrence is associated with late recurrence after radiofrequency ablation of atrial fibrillation
Authors: Wang Zhen , Lai Yiwei , Wang Yufeng , Wang Jue , Jiang Chao , He Liu , Guo Xueyan , Li Songnan , Wang Wei , Jiang Chenxi , Liu Nian , Tang Ribo , Long Deyong , Sang Caihua , Du Xin , Dong Jianzeng , Ma Changsheng
Published: July 2023

Aims

After radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF), the effect of very-early (within 48 h) symptomatic recurrence (VESR) on late (after 3 months of RFCA) recurrence (LR) has been seldomly reported. We aimed to explore the relationship between VESR and LR among post-RFCA patients.

Methods and results

This was a single-centre prospective cohort study that enrolled 6887 AF patients who received the first RFCA procedure from June 2018 to December 2021 at Beijing Anzhen Hospital. Patients were divided into four groups based on VESR and early (from 48 h to 3 months after RFCA) recurrence (ER): Group A (no VESR, no ER); Group B (VESR but no ER); Group C (ER but no VESR); and Group D (both VESR and ER). Three hundred and thirty (4.79%) patients experienced VESR (Groups B and D). With an average follow-up of 14.7 months after grouping, the Kaplan–Meier curve showed that LR risk in VESR patients was higher than in other patients (log-rank, P < 0.001), and the difference was significant in both paroxysmal (log-rank, P < 0.001) and persistent (log-rank, P < 0.001) AF patients (P for interaction = 0.118). In multivariate analysis, Groups B, C, and D were associated with a 2.161-, 5.409-, and 7.401-fold increase in the risk of LR, respectively. What is more, compared with Group A, VESR-atrial tachycardia and VESR-AF were related to a 3.467- and 5.564-fold LR risk, respectively. In VESR patients, classification based on ER and VESR modes improved the prediction potential of LR risk.

Conclusion

Very-early symptomatic recurrence is associated with an increased risk of LR.
Cascading foreshocks, aftershocks and earthquake swarms in a discrete fault network
Authors: Im Kyungjae , Avouac Jean-Philippe
Published: July 2023

Earthquakes come in clusters formed of mostly aftershock sequences, swarms and occasional foreshock sequences. This clustering is thought to result either from stress transfer among faults, a process referred to as cascading, or from transient loading by aseismic slip (pre-slip, afterslip or slow slip events). The ETAS statistical model is often used to quantify the fraction of clustering due to stress transfer and to assess the eventual need for aseismic slip to explain foreshocks or swarms. Another popular model of clustering relies on the earthquake nucleation model derived from experimental rate-and-state friction. According to this model, earthquakes cluster because they are time-advanced by the stress change imparted by the mainshock. This model ignores stress interactions among aftershocks and cannot explain foreshocks or swarms in the absence of transient loading. Here, we analyse foreshock, swarm and aftershock sequences resulting from cascades in a Discrete Fault Network model governed by rate-and-state friction. We show that the model produces realistic swarms, foreshocks and aftershocks. The Omori law, characterizing the temporal decay of aftershocks, emerges in all simulations independently of the assumed initial condition. In our simulations, the Omori law results from the earthquake nucleation process due to rate and state friction and from the heterogeneous stress changes due to the coseismic stress transfers. By contrast, the inverse Omori law, which characterizes the accelerating rate of foreshocks, emerges only in the simulations with a dense enough fault system. A high-density complex fault zone favours fault interactions and the emergence of an accelerating sequence of foreshocks. Seismicity catalogues generated with our discrete fault network model can generally be fitted with the ETAS model but with some material differences. In the discrete fault network simulations, fault interactions are weaker in aftershock sequences because they occur in a broader zone of lower fault density and because of the depletion of critically stressed faults. The productivity of the cascading process is, therefore, significantly higher in foreshocks than in aftershocks if fault zone complexity is high. This effect is not captured by the ETAS model of fault interactions. It follows that a foreshock acceleration stronger than expected from ETAS statistics does not necessarily require aseismic slip preceding the mainshock (pre-slip). It can be a manifestation of a cascading process enhanced by the topological properties of the fault network. Similarly, earthquake swarms might not always imply transient loading by aseismic slip, as they can emerge from stress interactions.
Phyllosphere bacterial strains Rhizobium b1 and Bacillus subtilis b2 control tomato leaf diseases caused by Pseudomonas syringae pv. tomato and Alternaria solani
Authors: Shao Ziyu , Schenk Peer M , Dart Peter
Published: July 2023

Aims

Show that tomato leaf phyllosphere bacteria are candidates for biocontrol of tomato leaf diseases.

Methods and Results

Seven bacterial isolates from surface-sterilized Moneymaker tomato plants were tested for growth inhibition of 14 tomato pathogens on potato dextrose agar. Biocontrol assays were conducted with tomato leaf pathogens, Pseudomonas syringae pv. tomato (Pto) and Alternaria solani (A. solani). Two potential isolates showing the greatest inhibition were identified by 16S rDNA sequencing as Rhizobium sp. (isolate b1) and Bacillus subtilis (isolate b2), both produce protease and isolate b2 cellulase. Both reduced tomato leaf infections by Pto and A. solani in detached leaf bioassays. Both bacteria b1 and b2 reduced pathogen development in a tomato growth trial. Bacteria b2 also induced the tomato plant salicylic acid (SA) immune response pathway. Disease suppression in biocontrol assays with b1 and b2 varied between five commercial tomato varieties.

Conclusions

Tomato phyllosphere bacteria when used as phyllosphere inoculants, inhibited tomato diseases caused by Pto and A. solani.
The NYU Data Catalog: a modular, flexible infrastructure for data discovery
Authors: Yee Michelle , Surkis Alisa , Lamb Ian , Contaxis Nicole
Published: July 2023

Objective

Researchers at New York University (NYU) Grossman School of Medicine contacted the Health Sciences Library for help with locating large datasets for reuse. In response, the library developed and maintained the NYU Data Catalog, a public-facing data catalog that has supported not only faculty acquisition of data but also the dissemination of the products of their research in various ways.

Materials and Methods

The current NYU Data Catalog is built upon the Symfony framework with a tailored metadata schema reflecting the scope of faculty research areas. The project team curates new resources, including datasets and supporting software code, and conducts quarterly and annual evaluations to assess user interactions with the NYU Data Catalog and opportunities for growth.

Results

Since its launch in 2015, the NYU Data Catalog underwent a number of changes prompted by an increase in the disciplines represented by faculty contributors. The catalog has also utilized faculty feedback to enhance support of data reuse and researcher collaboration through alterations to its schema, layout, and visibility of records.

Discussion

These findings demonstrate the flexibility of data catalogs as a platform for enabling the discovery of disparate sources of data. While not a repository, the NYU Data Catalog is well-positioned to support mandates for data sharing from study sponsors and publishers.

Conclusion

The NYU Data Catalog makes the most of the data that researchers share and can be harnessed as a modular and adaptable platform to promote data sharing as a cultural practice.
A call to action to improve the completeness of older adult sexual and gender minority data in electronic health records
Authors: May Jennifer T , Myers John , Noonan Devon , McConnell Eleanor , Cary Michael P
Published: July 2023

Sexual and gender minority (SGM) older adults experience greater health disparities compared to non-SGM older adults. The SGM older adult population is growing rapidly. To address this disparity and gain a better understanding of their unique challenges in healthcare relies on accurate data collection. We conducted a secondary data analysis of 2018–2022 electronic health record data for older adults aged ≥50 years, in 1 large academic health system to determine the source, magnitude, and correlates of missing sexual orientation and gender identity (SOGI) data among hospitalized older adults. Among 153 827 older adults discharged from the hospital, SOGI data missingness was 67.6% for sexual orientation and 63.0% for gender identity. SOGI data are underreported, leading to bias findings when studying health disparities. Without complete SOGI data, healthcare systems will not fully understand the unique needs of SGM individuals and develop tailored interventions and programs to reduce health disparities among these populations.
Effect of ellagic acid on body weight, nutrient digestibility, fecal microbiota, and urolithin A metabolism in Thoroughbred horses
Authors: Li Jiahao , Huang Xinxin , He Linjiao , Li Chao , Jing Hongxin , Lin Jianwei , Ma Chaoyu , Li Xiaobin
Published: July 2023

This study aimed to investigate the effects of ellagic acid (EA) supplementation on body weight (BW), nutrient digestibility, fecal microbiota, blood biochemical indices, and urolithin A metabolism in 1-yr-old Thoroughbred horses. A group of 18 1-yr-old Thoroughbred horses, with an average weight of 339.00 ± 30.11 kg, were randomly allocated into three groups of six horses each (three males and three females). The control group (n = 6) received only the basal diet, whereas test groups I (n = 6) and II (n = 6) were fed the basal diet supplemented with 15 mg/kg BW/d and 30 mg/kg BW/d of EA, respectively, for 40-d. The results showed that test group I and II horses had a significant increase in total weight gain by 49.47% and 62.74%, respectively, compared to the control group. The digestibility of various components in the diets of the test group horses was improved, including dry matter, organic matter, gross energy, neutral detergent fiber, acid detergent fiber, and calcium. Additionally, the digestibility of crude protein and phosphorus (P) in test group II horses increased significantly by 10.96% and 33.56% (P < 0.05), respectively. Moreover, EA supplementation significantly increased the fecal abundance of Firmicutes, Bacteroidetes (P < 0.05), Fibrobacterota, p-251-o5, Desemzia incerta (P < 0.05), and Fibrobacter sp. (P < 0.05), while reducing the abundance of Proteobacteria, Pseudomonadaceae, Pseudomonas, and Cupriavidus pauculus (P < 0.05 or P < 0.01). Fecal samples from test group II showed 89.47%, 100%, and 86.15% increases in the concentrations of acetic acid, valeric acid, and total volatile fatty acids, respectively. In addition, the plasma levels of total protein, and globulin increased significantly in test groups I (7.88% and 11.35%, respectively) and II (13.44% and 16.07%, respectively) compared to those in the control group (P < 0.05). The concentration of urolithin A in fecal and urine samples was positively correlated with increasing doses of EA. These findings suggest that supplemental feeding of EA improved nutrient digestibility, blood biochemical indices, and fecal microbiota in 1-yr-old Thoroughbred horses, promoting growth and development.
Immigration and seasonal bottlenecks: high inbreeding despite high genetic diversity in an oscillating population of Culicoides sonorensis (Diptera: Ceratopogonidae)
Authors: Shults Phillip , Zhang Xinmi , Moran Megan , Cohnstaedt Lee W , Gerry Alec C , Vargo Edward L , Eyer Pierre-Andre
Published: July 2023

Most population genetic studies concern spatial genetic differentiation, but far fewer aim at analyzing the temporal genetic changes that occur within populations. Vector species, including mosquitoes and biting midges, are often characterized by oscillating adult population densities, which may affect their dispersal, selection, and genetic diversity over time. Here, we used a population of Culicoides sonorensis from a single site in California to investigate short-term (intra-annual) and long-term (inter-annual) temporal variation in genetic diversity over a 3 yr period. This biting midge species is the primary vector of several viruses affecting both wildlife and livestock, thus a better understanding of the population dynamics of this species can help inform epidemiological studies. We found no significant genetic differentiation between months or years, and no correlation between adult populations and the inbreeding coefficient (FIS). However, we show that repeated periods of low adult abundance during cooler winter months resulted in recurring bottleneck events. Interestingly, we also found a high number of private and rare alleles, which suggests both a large, stable population, as well as a constant influx of migrants from nearby populations. Overall, we showed that the high number of migrants maintains a high level of genetic diversity by introducing new alleles, while this increased diversity is counterbalanced by recurrent bottleneck events potentially purging unfit alleles each year. These results highlight the temporal influences on population structure and genetic diversity in C. sonorensis and provide insight into factors effecting genetic variation that may occur in other vector species with fluctuating populations.