bluuebunny/crossref_metadata_2025 huggingface dataset:
Staging the bipolar disorders: Are early stages at too early a stage for intervention?
Authors: Parker Gordon
Published: September 2022

Objectives

A number of staging models have been generated for the bipolar disorders, which include pre‐onset as well as post‐onset stages. Some models propose treatments for those at the pre‐onset stage, a recommendation which is critiqued here.

Methods

Several exemplar staging models are overviewed, and a critique is provided.

Results

The critique argues against intervention at a pre‐onset stage, in light of there being limited risk factors, unquantified sensitivity and specificity data for most putative onset illness risk factors, and thus there is the risk of overtreatment. Also, it is possible that many of the recommended interventions for those at risk of a bipolar disorder may have general non‐specific benefits for those at risk.

Conclusions

While retaining a pre‐onset phase in the staging model, it would appear wiser for it to not be populated with recommended interventions until they have a firmer empirical base.
Stratification according to disease severity can better reveal the relative effectiveness of treatments for acne vulgaris
Authors: Evrenoglou Theodoros
Published: September 2022

Linked article:  Mavranezouli et al. Br J Dermatol 2022; 187:639–649.
Diversity in habit expands the environmental niche of Ziziphus (Rhamnaceae)
Authors: Rickenback Jess , Pennington R. Toby , Lehmann Caroline E. R.
Published: September 2022

Ziziphus (Rhamnaceae) is a widely distributed genus across the Australasian and African tropics with unusual diversity in habit, and many species of significance to people. Here, we quantify the environmental limits of Ziziphus species and examine inter‐specific relationships among functional traits, environment, biome, and range size. We developed a curated geolocation database for Ziziphus and used it to examine the environmental limits of the genus relative to temperature, rainfall, and seasonality. To assess the relationship between biome and habit, permutational analysis of variance was used, while hierarchical clustering was used to determine whether habit, leaves, and fruit traits were related to biome. For 40 species with adequate geolocation data, range size was calculated to assess its relationship with habit, biomes, and cultivation. Finally, niche identity tests were used to determine niche equivalency among cultivated and non‐cultivated species. Liana species are restricted to closed forests and the geoxylic habit is found only in open grasslands. Further, habit is significantly associated with range size, with trees having on average larger range sizes than shrubs, lianas, and geoxyles, but biome was not correlated with range size. Cultivated species have ranges ~10 times that of non‐cultivated tree species and with significantly different and broader environmental niches. The unusually wide distribution of Ziziphus can be explained by its diversity of habits associated with different biomes spanning continents. This, along with the usage of many Ziziphus species by people for their fruits, expands the range and environmental occupation of the genus.
Investigating self‐reported food allergy prevalence in Waterloo Region, Canada
Authors: Cardwell Francesca S. , Clarke Ann E. , Elliott Susan J.
Published: September 2022

While food allergy prevalence has been studied at the national level, we know little of food allergy prevalence or perceptions of prevalence/management at the local level. This paper uses Waterloo Region as a case study to 1) document self‐reported individual and household food allergy and sensitivity prevalence at the local level; 2) investigate perceptions of food allergy prevalence; and 3) explore perceived confidence in anaphylaxis management. Survey data were collected from January to March 2019. Respondents (n = 500) self‐reported individual and household food allergy and sensitivity, estimated the percentage of Canadians with food allergy, and were queried about their knowledge of food allergy management. Prevalence estimates were weighted to the structure of the 2016 Canadian Census, and univariate and bivariate analysis were conducted. Prevalence of self‐reported food allergy was 12.1% (95%CI, 8.8%‐15.3%), and prevalence of self‐reported food sensitivity was 26.3% (95%CI, 21.9%‐30.7%). When asked to estimate the percentage of Canadians with food allergy, the mean perceived percentage was 35.1% (SD = 22.96). Self‐reported prevalence of food allergy appears higher in Waterloo Region, and the estimated percentage of Canadians with food allergy is inflated. Understanding prevalence and perceptions at the local level is important for targeted allocation of public health resources to ensure safe spaces for individuals with food allergy.
Risk‐adapted stereotactic body radiotherapy for patients with cervical spinal metastases
Authors: Wang Huan‐Huan , Tian Shou‐Sen , Yang Jia‐Min , Sun Bing‐Sheng , Chen Ying , Song Yong‐Chun , Dong Yang , Wang Jing‐Sheng , Yuan Zhi‐Yong , Cui Yao‐Li , Meng Mao‐Bin
Published: September 2022

Owing to the complex anatomical structure and biomechanics, the current standard palliative treatments for cervical spinal metastases are associated with a high risk of recurrence and complications. Stereotactic body radiotherapy (SBRT) can provide radical dose to tumors while protecting normal organs to the maximum extent. However, the efficacy and safety of SBRT for cervical spinal metastases is not well characterized. Data from 71 patients with cervical spine metastases who were treated with SBRT using CyberKnife between 2006 and 2021 were obtained from our prospectively maintained database. Primary endpoint was pain response at 12 weeks following SBRT completion; secondary endpoints included local control (LC), overall survival (OS), and adverse events. Standard‐risk patients were planned to receive 30 Gy (range 21–36) with median fractions of 3 (range 1–3) and high‐risk patients 35 Gy (range 24–50) with median fractions of 5 (range 4–5) according to the spinal cord and esophagus dose constraints. The median follow‐up time was 17.07 months (range 3.1–118.9). After 12 weeks of SBRT completion, 54 (98.2%) of 55 patients with baseline pain achieved pain response and 46 (83.6%) achieved complete pain response. LC rates were 93.1% and 90% at 1 year and 2 year, respectively. The 1‐year and 2‐year OS rates were 66.2% and 37.4%, respectively. Eight patients experienced grades 1–4 adverse events (six vertebral compression fracture [VCF], five of them had VCF before SBRT; and two hemiparesis). No grade 5 adverse events were observed. Therefore, risk‐adapted SBRT for cervical spine metastases achieved high pain control and LC rates with acceptable adverse events.
Suppression of high mobility group box 1 in B16F10 tumor does not inhibit the induction of neoantigen‐specific T cells
Authors: Waki Kayoko , Ozawa Miyako , Yamada Akira
Published: September 2022

Accumulated clinical data of immune checkpoint blockades have suggested the importance of neoantigens in cancer immunity. Tumor antigens are released from dead cancer cells together with cellular components, such as damage‐associated molecular patterns (DAMPs), into the tumor microenvironment. We recently reported that high mobility group box 1 (HMGB1), a representative DAMP molecule, showed a negative impact on anti‐tumor immunity. However, a positive role of HMGB1 in the initiation of innate and subsequent adaptive immunity has also been demonstrated; thus, the effects of HMGB1 on anti‐tumor immunity have not been well understood. In this study, we identified nine immunogenic neoantigen epitopes of B16F10 murine melanoma cells and subsequently investigated the effects of suppression of HMGB1 on the induction of neoantigen‐specific immunity using HMGB1‐knockout tumors. Neoantigen‐reactive T cells were expanded in B16F10 tumor‐bearing mice, and T cell receptor repertoire analysis suggested that neoantigen‐reactive T cells were oligo‐clonally increased in B16F10 tumor bearers. An increase of neoantigen‐reactive T cells and oligoclonal expansion of the T cells were similarly detected in HMGB1‐knockout tumor‐bearing mice. The induction of neoantigen‐specific immunity under the suppression of HMGB1 in the tumor microenvironment shown in this study supports further development of combination therapy of HMGB1 suppression with neoantigen‐targeted cancer immunotherapies, including immune checkpoint blockade therapy.
Ecological validity in measuring parents’ executive function
Authors: Diercks Catherine M. , Gunther Kelley E. , Teti Douglas M. , Lunkenheimer Erika
Published: September 2022

Parents' executive functions (EFs), or cognitive skills facilitating thought and behavior management, are meaningful correlates of parenting behavior. EFs are theorized to support parents in inhibiting reactive responses, managing information during parent–child interactions, and adapting to novel developmental demands. Less effective EFs associate with risk for harsh parenting and physical abuse, underscoring the importance of research on parental EFs in promoting healthy child development. Yet, despite the strong theory, findings are mixed and reveal only modest effect sizes in relations between EFs and parenting. One explanation may be a lack of ecological validity in measuring parental EFs. Traditional measures of adult EFs have been used, but these are decontextualized and do not reflect the cognitively and emotionally demanding nature of parenting. In this article, we argue that new and adapted measures are needed. We discuss the role of EFs in parenting, review measurement, and offer suggestions for improvements in ecological validity.
The therapeutic potential of bone marrow‐derived macrophages in neurological diseases
Authors: Zhou Kai , Han Jinming , Wang Yafeng , Xu Yiran , Zhang Yaodong , Zhu Changlian
Published: September 2022

Circulating monocytes are precursors of both tissue macrophages and dendritic cells, and they can infiltrate the central nervous system (CNS) where they transform into bone marrow‐derived macrophages (BMDMs). BMDMs play essential roles in various CNS diseases, thus modulating BMDMs might be a way to treat these disorders because there are currently no efficient therapeutic methods available for most of these neurological diseases. Moreover, BMDMs can serve as promising gene delivery vehicles following bone marrow transplantation for otherwise incurable genetic CNS diseases. Understanding the distinct roles that BMDMs play in CNS diseases and their potential as gene delivery vehicles may provide new insights and opportunities for using BMDMs as therapeutic targets or delivery vehicles. This review attempts to comprehensively summarize the neurological diseases that might be treated by modulating BMDMs or by delivering gene therapies via BMDMs after bone marrow transplantation.
Glomerular macrophage index (GMI) in kidney transplant biopsies is associated with graft outcome
Authors: Mölne Johan , Nasic Salmir , Bröcker Verena , Stegmayr Bernd , Felldin Marie , Peters Björn
Published: September 2022

Background

Macrophages in renal transplants have been shown to participate in antibody‐mediated rejection and are associated with impaired renal function. We calculated the glomerular macrophage index (GMI) in a large transplant biopsy cohort, studied its quantity in different diagnostic groups, to clarify its possible impact on graft survival.

Methods

GMI, defined as the mean number of macrophages in 10 glomeruli, was prospectively quantified in 1440 renal transplant biopsies over a 10‐year period. The main histopathological diagnoses were grouped into eight disease entities, and GMI was compared to normal transplant biopsies as the reference group. The impact of GMI on graft survival was analyzed.

Results

GMI was highest in chronic (mean 9.4) and active (9.7) antibody mediated rejections (ABMR), mixed rejections (7.6), and recurrent or de novo glomerulonephritis (7.5) and differed significantly from normal transplants (1.3) in almost all diagnostic groups. Hazard ratios for graft loss were significantly increased for all biopsies with GMI ≥1.9 compared to GMI < .5 (reference group) in an adjusted Cox regression model and increased with higher GMI levels. Biopsies with GMI ≥ 4.6 had < 60% 10‐year graft‐survival, compared to > 80% with GMI ≤ 1.8.

Conclusion

GMI levels were predictive of graft loss independent of histological diagnoses and may guide clinicians to decide follow‐up and therapy.
Line‐field confocal optical coherence tomography of lentigo maligna with horizontal and vertical histopathologic correlations
Authors: Verzì Anna Elisa , Broggi Giuseppe , Caltabiano Rosario , Micali Giuseppe , Lacarrubba Francesco
Published: September 2022

Lentigo maligna (LM) is a subtype of in situ melanoma that classically presents in elderly patients as a slowly growing lesion on sun‐exposed areas that may evolve to invasive melanoma. Line‐field confocal optical coherence tomography (LC‐OCT) is a new non‐invasive technique for a real‐time, vertical, and horizontal skin imaging with high resolution close to conventional histopathology. We present the LC‐OCT features of an LM of the nose in a 49‐year‐old white man along with their horizontal and vertical histopathological correlations. LC‐OCT was able to detect in vivo, in both horizontal and vertical imaging, the main microscopic features typical of LM by showing, in the epidermis and around the hair follicles, the presence of large, bright roundish, or dendritic atypical cells, with evident nuclei, corresponding to atypical melanocytes with a tendency toward folliculotropism. A strong correspondence between LC‐OCT images and vertical and horizontal histopathological sections was observed. Our study, although limited to a single case, is indicative of the great potential of LC‐OCT to improve the non‐invasive diagnosis of LM.
Navigating social interactions and constructing vaping social identities: A qualitative exploration with New Zealand young adults who smoke
Authors: Blank Mei‐Ling , Hoek Janet
Published: September 2022

Introduction

Social interactions help smoking and vaping practices evolve, and are essential when constructing social identities. Among people who smoke, vaping offers an alternative practice to ‘smoking’ and ‘non‐smoking’, and using e‐cigarettes blurs the boundaries between ‘smoker’ and ‘non‐smoker’ social identities. In this study, we explored the development of vaping and smoking social identities over time among young adults who smoked and used e‐cigarettes.

Methods

Over 18–24 weeks during 2018–2019, we conducted five interviews with each of 11 New Zealand young adults aged 19–29 years who tried vaping to stop smoking. We analysed participants' interview transcripts for social interactions involving smoking or vaping and used social identity theory to explore their construction of vaping social identities.

Results

Participants entered the study with smoke‐free goals, and constructed social identities explicitly in relation to a smoke‐free transition. Two key identity processes, ‘adopting legitimacy’ and ‘transferring considerateness’, informed participants' social identity construction as they attempted to reconcile their e‐cigarette use with their pre‐study characterisations of vaping as ‘illegitimate’ and ‘obnoxious’. Our findings suggest that adopting a ‘legitimate’ vaper identity focussed on smoking cessation, and being perceived and accepted by others as a ‘legitimate vaper’, were essential in participants' identification as ‘vapers’. Identifying as a ‘legitimate’ vaper was a pre‐requisite to transferring a ‘considerate’ identity from smoking to vaping.

Discussion and Conclusion

Participants' construction of vaping social identities suggests that negotiating and reconciling valued aspects of a smoking social identity with nascent vaping practices may be important during smoking‐to‐vaping transition attempts.
Childhood separation from parents with cognitive and psychopathological outcomes in adolescence
Authors: Zhao Xudong , Zhang Anhui , Liu Wanxu , Tao Fangbiao , Sun Ying
Published: September 2022

To examine the effects of childhood parent‐child separation with varying duration and form on later cognitive performance and psychopathological problems over a 6‐year period, we use data from the China Family Panel Study (CFPS), which is an ongoing, prospective nationally representative study across 25 provinces in China. Of the 4033 children aged 4–10 years followed in 2012, 3522 children with complete data on separation from fathers and mothers were included. In 2018, 2560 participants were followed and interviewed to assess cognitive performance, behavioral problems as well as depressive symptoms at age 10–16 years. A total of 3522 children (mean [SD] age at baseline, 6.9 [2.0] years) were included. About 17.9% and 13.3% had separated from father and mother over 11 months or more in the year prior to the survey. Prolonged separation from parents was associated with lower scores in vocabulary (maternal: adjusted β = ‐1.64, P = 0.002; paternal: adjusted β = ‐1.58, P < 0.001) and mathematics performance (maternal: adjusted β = ‐1.10, P = 0.009; paternal: adjusted β = ‐0.94, P = 0.004) over a 6‐year period. Prolonged maternal separation was associated with 0.34‐point higher internalizing behaviors (P < 0.001) and 0.21‐point higher externalizing behaviors (P = 0.009), as well as 0.89‐point higher depressive symptoms (P = 0.018), while prolonged paternal separation was associated with 0.23‐point higher internalizing behaviors (P = 0.005) and 0.76‐point higher depressive symptoms (P = 0.011). The finding demonstrates substantial negative impacts of childhood paternal and maternal separations on cognitive and mental well‐being during adolescence, which might be dependent on the “stress‐dose” (duration of separation) and urban‐rural residence.

Research Highlights

Prolonged parent‐child separation is independently associated with cognitive impairment and psychopathological problems during adolescence.

The adverse effects of childhood separation on cognition and psychopathology varied by separation duration and separation forms.

Age‐ and residence‐specific associations between parent‐child separation with cognition and psychopathology are observed.
ex vivo–in vivo comparison of drug penetration analysis by confocal Raman microspectroscopy and tape stripping
Authors: Krombholz Richard , Fressle Stefanie , Nikolić Ines , Pantelić Ivana , Savić Snežana , Sakač Milkica Crevar , Lunter Dominique
Published: September 2022

When it comes to skin penetration analysis of a topically applied formulation, the number of suitable methods is limited, and they often lack in spatial resolution. In vivo studies are pivotal, especially in the approval of a new product, but high costs and ethical difficulties are limiting factors. For that reason, good ex vivo models for testing skin penetration are crucial. In this study, caffeine was used as a hydrophilic model drug, applied as a 2% (w/w) hydrogel, to compare different techniques for skin penetration analysis. Confocal Raman microspectroscopy (CRM) and tape stripping with subsequent HPLC analysis were used to quantify caffeine. Experiments were performed ex vivo and in vivo. Furthermore, the effect of 5% (w/w) 1,2‐pentanediol on caffeine skin penetration was tested, to compare those methods regarding their effectiveness in detecting differences between both formulations.
Interparental conflict predicts developmental trajectories of maternal sensitivity across early childhood
Authors: Trumbell Jill M. , Posada German , Anaya Laura
Published: September 2022

Objective

This study examined developmental trajectories of maternal sensitivity across early childhood and explored whether changes in sensitivity were predicted by changes in interparental conflict.

Background

Maternal sensitivity facilitates healthy child development. Previous research has elucidated the role of interparental conflict as a determinant of sensitivity, but we know little about the trajectory of sensitivity across early childhood and the extent to which interparental conflict over time impacts sensitivity.

Method

Mothers (n = 78) and their children were visited at the playground four times across early childhood (child age: 3.5 to 5.5 years). Observers reported on maternal sensitivity after each visit. Interparental conflict was self‐reported by mothers twice when their child was approximately 3.5 and 5 years old.

Results

On average, both conflict and sensitivity showed continuity across early childhood. However, hierarchical linear modeling indicated significant variability in trajectories of change in sensitivity based upon frequency of interparental conflict.

Conclusion

Although interparental conflict was relatively low at both times, mothers reporting increased conflict showed decreased sensitivity as their child aged.

Implications

Findings underscore the importance of studying mother–child relationships within the larger familial context and provide support for the playground as an ecologically valid context to assess sensitivity.
Enhanced thermal conductivity and flexural strength of sintered reaction‐bonded silicon nitride with addition of (Y0.96Eu0.04)2O3
Authors: Li Shishuai , Xia Yongfeng , Yao Dongxu , Liang Hanqin , Zeng Yu‐Ping
Published: September 2022

Sintered reaction‐bonded silicon nitride (SRBSN) with high thermal conductivity was obtained using (Y0.96Eu0.04)2O3 and MgO as sintering additives. Green compacts were nitrided at 1400°C for 4 h. Post‐sintering was carried out at 1850 and 1900°C for 4 h, respectively. In reaction‐bonded silicon nitride (RBSN) doped with Y2O3 and MgO, the β‐Si3N4 content and nitridation degree were 51.1% and 93.8%, respectively. However, the β‐Si3N4 content and nitridation degree were 72.6% and 96.7% in a nitrided compact doped with (Y0.96Eu0.04)2O3 and MgO. After post‐sintering, the phase composition, microstructure, mechanical properties, and thermal conductivity were investigated. After sintering at 1900°C for 4 h, the thermal conductivity of SRBSN doped with (Y0.96Eu0.04)2O3 and MgO was increased by 16.5% compared to that of the samples doped with Y2O3 and MgO. The highest hardness of 1639 HV and the good flexural strength of 776.4 MPa were also achieved in the sample doped with 2‐mol.% (Y0.96Eu0.04)2O3 and 5‐mol.% MgO.
Valorisation of kinnow peel for development of phytochemical enriched tea infusion: standardisation of tea bag loading, dipping temperature and dips per minute for the better extraction of bioactive compounds
Authors: Bassi Pratishtha , Kumar Vikas , Kaur Ramandeep , Kumar Satish , Saini Ramesh Kumar , Janghu Sandeep
Published: September 2022

In recent years, the risk of catastrophic conditions has increased with the changed environmental conditions. Herbal teas are an ideal way to provide phytocompounds having specific health benefits to the consumers. In this study, herbal tea infusion was prepared with the pre‐standardised dried kinnow peel, herbs and spices. Extraction of the polyphenols mainly depends on the bag loading and steeping conditions. Therefore, the aim of the present study was to optimise the dipping conditions for the maximum extraction of phytocompounds. The effect of three process variables conditions, that is, tea bag loading (1–3 g), dipping temperature (75–95 °C) and dips per minute (5–20) was evaluated. Among the three variables, tea bag loading and the number of dips per minute significantly (P ≤ 0.05) affect all the quality attributes. These results were also confirmed during cluster analysis. Hence, it was concluded that optimised conditions result in maximum delivery of bioactive compounds under adverse conditions.
SMART goals of children of 6–12 years enrolled in a family‐centred lifestyle intervention for childhood obesity: Secondary analysis of a randomized controlled trial
Authors: Deslippe Alysha L. , Bains Andy , Loiselle Sarah‐Eve , Kasvis Popi , Mak Ivy , Weiler Hope , Cohen Tamara R.
Published: September 2022

This study demonstrates how SMART (Specific, Measurable, Attainable, Realistic and Timely) goals set by children in a lifestyle intervention contributed favorably to weight outcomes. Children (6‐12 years) set goals with a registered dietitian over six months. Goals were classified according to their type (diet or activity), direction, (increase healthy or decrease unhealthy), and theoretical constructs. Theoretical constructs included the Theory of Planned Behavior's attitudes (i.e., changing beliefs about behaviour outcomes), subjective norm (i.e., incorporation of health recommendations) and perceived behavioural control (i.e., over goal barriers and facilitators). Constructs from a Socio‐Ecological Model (family or individual) were also applied. Participants who maintained or decreased their body mass index for‐age‐and‐sex z‐scores (BAZ) after six months created significantly more goals related to the subjective norm compared to those whose BAZ increased (p = 0.003). Future interventions using SMART goals should incorporate health recommendations (i.e., the subjective norm) through actionable items among children to promote success.
Stock market, credit market, and heterogeneous innovations
Authors: Wang Xun
Published: September 2022

The relative importance of credit market development and stock market development in boosting innovation remains a long‐standing debate issue. In this study, we document how different types of financial markets development affect heterogeneous innovations. Using a broad sample across 42 developed and emerging economies and a generalized difference‐in‐differences identification strategy, we find that stock market development leads to significantly higher substantive innovation, especially in young and small firms, but has negative impact on incremental innovation. Conversely, credit market development promotes incremental innovation, especially in mature and large firms, but has negative impact on substantive innovation. Further analyses indicate that stronger shareholder protection enhances the positive impact of stock market on substantive innovation, while stronger creditor rights enhance the promoting effect of credit market on incremental innovation, and even turn the negative impact of credit market on substantive innovation into positive. Our paper provides new insights into the heterogeneous effects of credit market and equity markets on the real economy.
Influences of powder morphology on the densification and microstructure of a ZrO2‐based nanocrystalline glass–ceramic
Authors: Fu Le , Li Lei , Cheng Yongxin , Wang Bohan , Wu Hui
Published: September 2022

Morphology is an important characteristic of raw powder utilized for ceramic sintering but the role of powder morphology is mostly overlooked. In this study, two types of ZrO2–SiO2 powder with different morphologies (fiber and particle) were synthesized by blow spinning and sol–gel method, respectively, followed by direct current electric field‐assisted hot pressing (FAHP) to obtain nanocrystalline glass–ceramics (NCGCs). Results showed that the two as‐synthesized powders had different pyrolysis behaviors. The two types of as‐synthesized powders were amorphous and tetragonal‐ZrO2 nanocrystallites first formed after calcination at 800°C. During FAHP, the particle powder can be densified at a lower temperature than that of the fiber powder, due to the facts that the particle powder showed higher specific surface area and higher densification driving force. The fiber powder was predominately densified by fiber fusion and plastic deformation, whereas the particle powder was densified via particle fusion. Both the two types of powder can be fully densified to obtain ZrO2–SiO2 NCGCs at 1230°C for 4 min. Tetragonal‐ZrO2 nanocrystallites in the NCGCs with particles as raw powder showed higher stability than those in the NCGCs with fibers as raw powder.
Ultrasound-assisted facile synthesis of Boron-Heck-coupled sclareol analogues as potential antibacterial agents against Staphylococcus aureus
Authors: Jameel Salman , Farooq Sadaqat , Gani Ifshana , Riyaz-Ul-Hassan Syed , Bhat Khursheed Ahmad
Published: September 2022

Aim

To evaluate the antimicrobial capability of sclareol and its derivatives against Staphylococcus aureus and its Methicillin-resistant strain (MRSA).

Methods and Results.

A new series of Boron-Heck-coupled sclareol analogues were prepared by structural modifications at the C-15 terminal double bond of sclareol using ultrasonication. The structural modifications were designed to keep the stereochemistry of all the five chiral centres of sclareol intact. A two-step reaction scheme consisting of Boron-Heck coupling of sclareol followed by Wittig reaction was carried out to produce novel sclareol congeners for antimicrobial evaluation. Three compounds SAJ-1, SAJ-2 and SB-11 exhibited strong antibacterial activity against S. aureus and Methicillin-resistant strain (MRSA) with MIC values between 3 and 11 μM. Among all the screened compounds, SAJ-1 and SAJ-2 showed the best antibiofilm profiles against both strains. Moreover, SAJ-1 and SAJ-2 acted synergistically with streptomycin against S. aureus while creating varying outcomes in combination with ciprofloxacin, penicillin and ampicillin. SAJ-1 also acted synergistically with ampicillin against S. aureus, while SB-11 showed synergism with ciprofloxacin against both pathogens. Moreover, SAJ-1 and SAJ-2 also inhibited staphyloxanthin production in S. aureus and MRSA and induced postantibiotic effects against both pathogens.

Conclusions

It can be inferred that SAJ-1, SAJ-2 and SB-11 may act as potential chemical entities for the development of antibacterial substances. The study revealed that SAJ-1 and SAJ-2 are the most suitable sclareol analogues for further studies towards the development of antibacterial substances.

Significance and Impact of the Study

SAJ-1, SAJ-2 and SB-11 show promising antibacterial properties against Staphylococcus aureus. Efforts should be made and more research should be done utilizing in vivo models to determine their efficacy as antibiotics.
A mixed‐methods systematic review of nurse‐led interventions for people with multimorbidity
Authors: McParland Chris , Johnston Bridget , Cooper Mark
Published: September 2022

Aims

To identify types of nurse‐led interventions for multimorbidity and which outcomes are positively affected by them.

Design

Mixed‐methods systematic review following the Joanna Briggs Institute (JBI) methods for convergent‐integrated reviews. PROSPERO ID: CRD42020197956.

Data Sources

Cochrane CENTRAL, CINAHL, Embase and MEDLINE were searched in October 2020. Grey literature sources included OpenGrey, the Journal of Multimorbidity and Comorbidity and reference mining.

Review Methods

English‐language reports of nurse‐led interventions for people with multimorbidity were included based on author consensus. Two reviewers performed independent quality appraisal using JBI tools. Data were extracted and synthesized using a pre‐existing taxonomy of interventions and core outcome set.

Results

Twenty studies were included, with a median summary quality score of 77.5%. Interventions were mostly case‐management or transitional care interventions, with nurses in advanced practice, support to self‐manage conditions, and an emphasis on continuity of care featuring frequently. Patient‐centred outcomes such as quality of healthcare and health‐related quality of life were mostly improved, with mixed effects on healthcare utilization, costs, mortality and other outcomes.

Conclusion

Interventions such as case management are agreeable to patients and transitional care interventions may have a small positive impact on healthcare utilization. Interventions include long‐term patient management or short‐term interventions targeted at high‐risk junctures. These interventions feature nurses in advanced practice developing care plans in partnership with patients, to simplify and improve the quality of care both in the long and short‐term.

Impact

This is the first mixed‐methods review which includes all types of nurse‐led interventions for multimorbidity and does not focus on specific comorbidities or elderly/frail populations. Using adapted consensus‐developed frameworks for interventions and outcomes, we have identified the common features of interventions and their overall typology. We suggest these interventions are of value to patients and healthcare systems but require localization and granular evaluation of their components to maximize potential benefits.
Interaction between HER2 and ATM predicts poor survival in bladder cancer patients
Authors: Albarakati Nada , Al‐Shareeda Alaa , Ramadan Majed , Al‐Sowayan Batla , Negm Ola , Nedjadi Taoufik
Published: September 2022

Human Epidermal Growth Factor Receptor 2 (HER2) overexpression is considered one of the interesting prognostic biomarkers in bladder cancer. However, the mechanism of bladder cancer development in relation to HER2 status remains to be elucidated. In this study, we investigated HER2‐Ataxia telangiectasia mutated (ATM) kinase interaction and their impact on patient survival and cancer aggressiveness. Using the Cancer Genome Atlas (TCGA) cohorts, we demonstrated that ATM expression (protein/mRNA) is increased in HER2 deficient compared with proficient HER2 patients. This finding was then validated using the Gene Expression Omnibus database (GEO). Correlation analysis (using low expression vs high expression as a discriminator) revealed a significant association of ATM low and HER2 high status with several clinicopathological variables such as high tumour grade, late disease stage and tumour shape. Kaplan–Meier survival analysis indicated that ATM low and HER2 high is a powerful prognosticator of both overall survival (OS) and disease‐free survival (DFS). Furthermore, using bioinformatics and protein/protein interaction analyses, we identified 66 putative overlapping proteins with direct link between HER2 and ATM most of which are functionally involved in transcription regulation, apoptotic process and cell proliferation. Interestingly, the results showed that these proteins are strongly linked with PI3K‐Akt pathway, p53 pathway and microRNAs in cancer. Altogether, our data pinpoint an important biological role of the interconnection between HER2 and ATM. The latter appear to be an independent prognostic biomarker and may serve as targets to develop novel combination therapies to improve the outcome of patients with bladder cancer.
Transcription factors are potential therapeutic targets in epilepsy
Authors: Sun Qihan , Xu Wenbo , Piao Jingjing , Su Jingyun , Ge Tongtong , Cui Ranji , Yang Wei , Li Bingjin
Published: September 2022

Academics generally believe that imbalance between excitation and inhibition of the nervous system is the root cause of epilepsy. However, the aetiology of epilepsy is complex, and its pathogenesis remains unclear. Many studies have shown that epilepsy is closely related to genetic factors. Additionally, the involvement of a variety of tumour‐related transcription factors in the pathogenesis of epilepsy has been confirmed, which also confirms the heredity of epilepsy. In this review, we summarize the existing research on a variety of transcription factors and epilepsy and present relevant evidence related to transcription factors that may be targets in epilepsy. This information is of great significance for revealing the in‐depth molecular and cellular mechanisms of epilepsy.
Clinical characteristics and outcomes of newly diagnosed patients with HIV‐associated aggressive B‐cell NHL in China
Authors: Wang Chaoyu , Liu Jun , Lei Haike , Li Yu , Wu Jian , Guo Bingling , Hu Renzhi , Liu Tingting , Wu Jing , Ding Yao , Hu Chongling , Liang Shunsi , Xiao Chunyan , Liang Xiping , Huang Dehong , Yang Tao , Zhang Wenjun , Yang Zailin , Li Jieping , Nan Yingyu , Li Qiying , Xiang Ying , Li Zhenhua , Wu Yongzhong , Liu Yao
Published: September 2022

Little is known about the incidence, clinical characteristics and prognostic factors in HIV associated lymphoma as these are less common than HIV‐negative lymphoma in China. Currently, there are no standard guidelines for treatment of these patients. Therefore, we performed a study to analyse the clinical characteristics and outcomes of newly diagnosed HIV‐associated aggressive B‐cell non‐Hodgkin's lymphoma (NHL) patients in Chongqing University Cancer Hospital (CUCH). Totally 86 newly diagnosed HIV‐associated aggressive B‐cell NHL patients in CUCH, southwest China, from July 2008 to August 2021, were analysed. In the entire cohort, median age was 48 years (range, 23–87 years), and more patients were male (87.2%). Most patients had elevated lactate dehydrogenase (LDH) (82.6%), advanced ann arbor stage (80.2%) and high IPI score (IPI score, 3–5) (62.7%) at diagnosis. Median CD4+ T‐cell count at diagnosis was 191/μl (range, 4–1022), 84 patients (97.7%) were on combination antiretroviral therapy (cART) at lymphoma diagnosis. In DLBCL patients, cox multivariate analysis showed that age ≥ 60 (HR = 2.251, 95%CI 1.122–4.516; p = 0.012), elevated LDH (HR = 4.452, 95%CI 1.027–19.297; p = 0.041) and received less than two cycles of chemotherapy (HR = 0.629, 95%CI 0.589–1.071; p = 0.012) were independent risk factors for adverse prognosis based on PFS. Age ≥ 60 (HR = 3.162, 95%CI 1.500–6.665; p = 0.002) and received less than two cycles of chemotherapy (HR = 0.524, 95%CI 0.347–0.791; p = 0.002) were also independent risk factor for adverse prognosis based on OS. In BL patients, cox multivariate analysis showed that elevated LDH and received less than two cycles of chemotherapy were independent risk factors for adverse prognosis. In the DLBCL group, median PFS times in the received rituximab and no received rituximab groups were not reached and 12 months, respectively (p = 0.006). Median OS times were not reached and 36 months, respectively (p = 0.021). In the BL group, median PFS times in the received rituximab and no received rituximab groups were not reached and 4.8 months, respectively (p = 0.046). Median OS times were not reached and 10.1 months, respectively (p = 0.035). Overall, these data indicated that standardized anti‐lymphoma therapy and rituximab administration were significantly associated with improved outcomes in patients with HIV‐associated DLBCL and BL.
Real‐world effectiveness and safety of tildrakizumab in long‐term treatment of plaque psoriasis: Results from the non‐interventional, prospective, multicentre study TILOT
Authors: Tsianakas Athanasios , Schwichtenberg Uwe , Pierchalla Peter , Hinz Torsten , Diemert Sebastian , Korge Bernhard
Published: September 2022

Background

Plaque psoriasis is a chronic inflammatory disorder affecting the skin and impacting quality of life. Tildrakizumab (TIL) is an IL‐23 inhibitor licensed for moderate‐to‐severe plaque psoriasis. Regulatory approval of medicinal products is based on safety and efficacy data from randomized controlled trials (RCTs) which impose stringent selection criteria. Long‐term non‐interventional studies (NIS) are needed to establish effectiveness and safety in daily practice bridging the gap between RCTs and the real‐world setting.

Objectives

This analysis of the NIS TILOT seeks to evaluate effectiveness and safety of TIL in patients with moderate‐to‐severe plaque psoriasis in a real‐world setting. Secondary objectives include the assessment of the Dermatology Life Quality Index (DLQI), treatment satisfaction and course of scalp and nail disease using Physician Global Assessment (PGA).

Methods

Interim analysis at 52 weeks (W) of the ongoing non‐interventional, prospective, long‐term multicentre study TILOT.

Results

The effectiveness analysis included 412 patients. The mean [standard deviation, SD] Psoriasis Area and Severity Index (PASI) score was 16.0 [9.1] at baseline improving by 82.4% (95% confidence interval [CI], 78.9–86.0) to 2.1 [2.9] at W52. The proportion of patients achieving PASI scores of <3 and <5 increased over time peaking at 74.6% (95% CI, 69.3–79.4) and 88.4% (95% CI, 84.3–91.8) at W52. Scalp‐PGA and nail‐PGA improved by 79.8% (95% CI, 75.6–84.0) and 72.7% (95% CI, 63.9–81.6), respectively. DLQI of 0/1 was achieved by 48.2% (95% CI, 42.3–54.2). Nine out of 10 physicians and patients expressed a high level of treatment satisfaction. No new safety signals were observed.

Conclusions

This prospective cohort study demonstrates a high degree of effectiveness and a reassuring safety profile of TIL in a real‐world setting over 52 weeks. Patients with scalp and nail involvement or pruritus showed marked improvements.
A New Bayesian Person‐Fit Analysis Method Using Pivotal Discrepancy Measures
Authors: Combs Adam
Published: September 2022

A common method of checking person‐fit in Bayesian item response theory (IRT) is the posterior‐predictive (PP) method. In recent years, more powerful approaches have been proposed that are based on resampling methods using the popular statistic. There has also been proposed a new Bayesian model checking method based on pivotal discrepancy measures (PDMs). A PDM T is a discrepancy measure that is a pivotal quantity with a known reference distribution. A posterior sample of T can be generated using standard Markov chain Monte Carlo output, and a p‐value is obtained from probability bounds computed on order statistics of the sample. In this paper, we propose a general procedure to apply this PDM method to person‐fit checking in IRT models. We illustrate this using the and measures. Simulation studies are done comparing these with the PP method and one of the more recent resampling methods. The results show that the PDM method is more powerful than the PP method. Under certain conditions, it is more powerful than the resampling method, while in others, it is less. The PDM method is also applied to a real data set.
An artificial neural network‐hydrodynamic coupled modeling approach to assess the impacts of floods under changing climate in the East Rapti Watershed, Nepal
Authors: Bhattarai Roshika , Bhattarai Utsav , Pandey Vishnu Prasad , Bhattarai Pawan Kumar
Published: September 2022

Recurring floods have devastating consequences on the East Rapti Watershed (ERW), but effective mitigation/adaptation measures are lacking. This article aims at establishing a rainfall‐runoff (RR) relationship; estimating depth and extent of inundation under climate change scenarios; assessing impacts on the socio‐economy; and identifying and evaluating adaptation strategies in the ERW. Artificial Neural Network (ANN) was used to generate peak flows which were then entered into a hydraulic model to simulate inundation. Results were validated with field survey. The calibrated and validated RR and hydraulic models were fed with projected future climate (2021–2050) derived from multiple regional‐climate‐models to assess the changes in inundation. Results showed the peak discharge likely exceeds 10,500 m3/s at the ERW outlet in the extreme future flood scenario with corresponding inundation of 80 km2 and up to a depth of 11 m sweeping away over 1000 houses and 19 km2 of agricultural land in the critical areas. Constructing a 17 km long embankment in the critical areas along the right bank of the East Rapti River could reduce the flood spread by 35%, safeguarding 78% of the houses and saving 51% agricultural land compared with the scenarios without the embankment.
Response to COVID‐19 vaccine is reduced in patients with inflammatory bowel disease, but improved with additional dose
Authors: Shiga Hisashi , Kakuta Yoichi , An Kumiko , Abe Yuko , Fujimaki Shinichi , Shimoyama Yusuke , Naito Takeo , Moroi Rintaro , Kuroha Masatake , Khor Seik‐Soon , Kawai Yosuke , Tokunaga Katsushi , Kinouchi Yoshitaka , Masamune Atsushi
Published: September 2022

Background

Coronavirus disease 2019 (COVID‐19) vaccination is recommended for patients with inflammatory bowel disease (IBD); however, suppressed immune responses have been reported for fully vaccinated patients under immunosuppressive therapy, mainly from Western countries. We prospectively analyzed antibody titers of IBD patients in Asia induced by two‐dose and additional dose of messengerRNA COVID‐19 vaccine.

Methods

After measuring high‐affinity antibody titers, factors associated with antibody titers were identified by multiple regression analyses using the following covariates: sex, age (≥60 or <60 years), disease type (Crohn's disease or ulcerative colitis), vaccine type (BNT162b2 or mRNA‐1273), time from second/third vaccination, molecular‐targeted agent (anti‐tumor necrosis factor [TNF] agents, ustekinumab, vedolizumab, tofacitinib, or no molecular‐targeted agents), thiopurine, steroid, and 5‐aminosalicylic acid.

Results

Among 409 patients analyzed, mean titer was 1316.7 U/mL (SD, 1799.3); 403 (98.5%) were judged to be seropositive (≥0.8 U/mL), and 389 (95.1%) had neutralizing antibodies (≥15 U/mL). After the third vaccination, mean titer raised up to 21 123.8 U/mL (SD, 23 474.5); all 179 were seropositive, and 178 (99.4%) had neutralizing antibodies. In 248 patients with genetic data, there was no difference in mean titer after two/third doses between carriers and non‐carriers of HLA‐A24 associated with severe disease during COVID‐19 infection. A multiple regression analyses using covariates revealed that older age, vaccine type (BNT162b2), time from second/third dose, anti‐TNF agent, tofacitinib, and thiopurine were independently associated with lower antibody titers.

Conclusions

Our findings further support the recommendation for COVID‐19 vaccination in patients under immunosuppressive therapy, especially additional third dose for patients receiving anti‐TNF agents and/or thiopurine or tofacitinib.
Automated particle recognition for engine soot nanoparticles
Authors: Haffner‐Staton E. , Avanzini L. , La Rocca A. , Pfau S. A. , Cairns A.
Published: September 2022

A pre‐trained convolution neural network based on residual error functions (ResNet) was applied to the classification of soot and non‐soot carbon nanoparticles in TEM images. Two depths of ResNet, one 18 layers deep and the other 50 layers deep, were trained using training‐validation sets of increasing size (containing 100, 400 and 1400 images) and were assessed using an independent test set of 200 images. Network training was optimised in terms of mini‐batch size, learning rate and training length. In all tests, ResNet18 and ResNet50 had statistically similar performances, though ResNet18 required only 25–35% of the training time of ResNet50. Training using the 100‐, 400‐ and 1400‐image training‐validation sets led to classification accuracies of 84%, 88% and 95%, respectively. ResNet18 and ResNet50 were also compared for their ability to categorise soot and non‐soot nanoparticles via a fivefold cross‐validation experiment using the entire set of 800 images of soot and 800 images of non‐soot. Cross‐validation was repeated 3 times with different training durations. For all cross‐validation experiments, classification accuracy exceeded 91%, with no statistical differences between any of the network trainings. The most efficient network was ResNet18 trained for 5 epochs, which reached 91.2% classification after only 84 s of training on 1600 images. Use of ResNet for classification of 1000 images, the amount suggested for reliable characterisation of soot sample, requires <4 s, compared with >30 min for a skilled operator classifying images manually. Use of convolution neural networks for classification of soot and non‐soot nanoparticles in TEM images is highly promising, particularly when manually classified data sets have already been established.