bluuebunny/crossref_metadata_2025 huggingface dataset:
Editorial: an accurate, reliable and responsive ultrasound activity score for Crohn’s disease? Sounds good to US
Authors: Goodsall T.M. , Bryant R.V.
Published: January 2022

LINKED CONTENT

This article is linked to Allocca et al papers. To view these articles, visit https://doi.org/10.1111/apt.16700 and https://doi.org/10.1111/apt.16754
Letter: the hidden reasons of long‐term risk of upper gastrointestinal bleeding after Helicobacter pylori eradication
Authors: Yang Hang , Hu Bing
Published: January 2022

LINKED CONTENT

This article is linked to Jiang et al papers. To view these articles, visit https://doi.org/10.1111/apt.16604 and https://doi.org/10.1111/apt.16746
Editorial: real‐world safety of tofacitinib in ulcerative colitis
Authors: Taxonera Carlos
Published: January 2022

LINKED CONTENT

This article is linked to Sandborn et al papers. To view these articles, visit https://doi.org/10.1111/apt.16712
Editorial: testing for Epstein Barr virus and treating autoimmune hepatitis—still a long way to go! Authors' reply
Authors: Nayagam Jeremy S. , Heneghan Michael A. , Samyn Marianne , Joshi Deepak
Published: January 2022

LINKED CONTENT

This article is linked to Nayagam et al papers. To view these articles, visit https://doi.org/10.1111/apt.16708 and https://doi.org/10.1111/apt.16751
Youth crime and depictions of youth crime in Canada: Are news depictions purely moral panic?
Authors: Silcox Jennifer
Published: January 2022

Scholars have highlighted the ways media often exaggerate and sensationalize crime in the western world. Nevertheless, it remains unclear whether the media's portrayal of youth crime offers an objective assessment of real‐world social problems, a sensationalized reflection of real‐world trends, or whether it signals a moral panic surrounding youth crime and violence. The purpose of the paper is to examine newspaper accounts of youth crime in comparison to official youth crime statistics and to determine whether, and to what extent, they align. If they do not align, can the existence of a moral panic be said to influence news portrayals of Canadian youth in conflict with the law?
Normal‐tension glaucoma: Current concepts and approaches‐A review
Authors: Leung Dexter Y. L. , Tham Clement C.
Published: January 2022

Normal tension glaucoma (NTG) has remained a challenging disease. We review, from an epidemiological perspective, why we should redefine normality, act earlier at lower pre‐treatment intraocular pressure (IOP) level, and the role of ocular perfusion pressures, noting that perfusion is affected by defective vascular bed autoregulation and endothelial dysfunction. The correlation of silent cerebral infarcts (SCI) and NTG may indicate that NTG belongs to a wider spectrum of small vessel diseases (SVD), with its main pathology being also on vascular endothelium. Epidemiological studies also suggested that vascular geometry, such as fractal dimension, may affect perfusion efficiency, occurrence of SCI, SVD and glaucoma. Artificial intelligence with deep learning, may help predicting NTG progression from vascular geometry. Finally, we review latest evidence on the role of minimally‐invasive glaucoma surgery, lasers, and newer drugs. We conclude that IOP is not the only modifiable risk factors as, many vascular risk factors are readily modifiable.
Additional preconditioning program for bariatric surgery: Any benefits? A large cohort study
Authors: van der Ven Roos G. F. M. , de Vos Rien , Lodewijks Yentl , van Hout Gerbrand C. M. , Lichthart Sacha , Nienhuijs Simon W.
Published: January 2022

Postbariatric outcomes may improve by providing an additional preconditioning program (APP) in targeted patients. However, APPs are a demand for health resources while only little and inconsistent evidence consists to support their effectiveness. This cohort study aims to evaluate the effectiveness of APP, by comparing outcomes of patients with and without such APP. We carried out a retrospective single‐centre cohort study in a before‐after design. Patients signing up for primary gastric bypass or sleeve gastrectomy and eligible for surgery were included if screened as vulnerable patients. Vulnerable patients screened between September 2017 and March 2018 followed an APP and formed the APP‐group. Due to a policy change, APPs were no longer performed since September 2018. Vulnerable patients screened between September 2018 and March 2019 thus did not receive an APP (comparator‐group). Multidisciplinary follow‐up remained unchanged. Endpoints included percentage total weight loss (%TWL), bodyweight, evolution of comorbidities, protein intake, and number of no‐shows. The APP‐group comprised 231 patients and the comparator‐group 153. %TWL differed statistically significantly at 7 (Δ1.5%, p = .01) and 12 months postoperative (Δ2.8%, p < .01) in favour of the comparator‐group, as did bodyweight 12 months postoperative (Δ1.8 kg, p < .01). Statistically significant differences were also found in the evolution of comorbidities, protein intake, and the number of no‐shows, most in favour for the comparator‐group. APP proofed not to be superior to Non‐App. It is debatable whether statically significant differences are clinically relevant given their small magnitude. A care pathway without an APP seems at least as effective as a care pathway without.
Availability of PEth testing is associated with reduced eligibility for liver transplant among patients with alcohol‐related liver disease
Authors: Selim Ranya , Zhou Yueren , Rupp Loralee B. , Trudeau Sheri , Naffouj Sandra , Shamaa Omar , Ahmed Abdelwahab , Jafri Syed‐Mohammed , Gordon Stuart C. , Segal Antu , Gonzalez Humberto C.
Published: January 2022

Background

Serum phosphatidylethanol (PEth) is a highly sensitive test to detect alcohol use. We evaluated whether the availability of PEth testing impacted rates of liver transplant evaluation terminations and delistings.

Methods

Medical record data were collected for patients who initiated transplant evaluation due to alcohol‐related liver disease in the pre‐PEth (2017) or PEth (2019) eras. Inverse probability weighting (IPW) was used to balance baseline patient characteristics. Outcomes included termination of evaluation or delisting due to alcohol use; patients were censored at receipt of transplant; death was considered a competing risk. The Fine‐Gray method was performed to determine whether PEth testing affected risk of evaluation termination/ delisting due to alcohol use.

Results

Three hundred and seventy‐five patients with alcohol‐related indications for transplant (157 in 2017; 210 in 2019) were included. The final IPW‐adjusted model for the composite outcome of terminations/delisting due to alcohol use retained two significant variables (P < .05): PEth era and BMI category. Patients evaluated during the PEth era were almost three times more likely to experience an alcohol‐related termination/delisting than those in the pre‐PEth era (sHR = 2.86; 95%CI 1.67–4.97)

Conclusion

We found that availability of PEth testing at our institution was associated with a higher rate of exclusion of patients from eligibility for liver transplant. Use of PEth testing has significant potential to inform decisions regarding transplant candidacy for patients with alcohol‐related liver disease.
Population pharmacokinetic and exposure‐response analyses from ALTA‐1L: Model‐based analyses supporting the brigatinib dose in ALK‐positive NSCLC
Authors: Gupta Neeraj , Reckamp Karen L. , Camidge David R. , Kleijn Huub J. , Ouerdani Aziz , Bellanti Francesco , Maringwa John , Hanley Michael J. , Wang Shining , Zhang Pingkuan , Venkatakrishnan Karthik
Published: January 2022

The ALK in Lung Cancer Trial of brigAtinib in First Line (ALTA‐1L) compared brigatinib versus crizotinib in anaplastic lymphoma kinase (ALK) inhibitor‐naive patients with ALK+ non‐small cell lung cancer (NSCLC). A population pharmacokinetic (PK) model was used to estimate brigatinib exposures for exposure‐efficacy and exposure‐safety analyses in ALTA‐1L. A previously developed population PK model for brigatinib was applied to estimate brigatinib PK parameters. Relationships between static (time‐independent) and dynamic (time‐varying) exposure metrics and efficacy (progression‐free survival [PFS], objective response rate [ORR], and intracranial ORR [iORR]) and safety outcomes (selected grade ≥2 and grade ≥3 adverse events [AEs]) were evaluated using logistic regression and time‐to‐event analyses. There were no meaningful differences in brigatinib PK in the first‐line and second‐line settings, supporting use of the previous population PK model for the first‐line population. Exposure‐response analyses showed no significant effect of time‐varying brigatinib exposure on PFS. Brigatinib exposure was not significantly related to ORR, but higher exposure was associated with higher iORR (odds ratio: 1.13, 95% confidence interval: 1.01–1.28, p = 0.049). Across the observed median exposure (5th–95th percentile) at steady state for 180 mg once daily, the predicted probability of iORR was 0.83 (0.58–0.99). AEs significantly associated with higher exposure were elevated lipase (grade ≥3) and amylase (grade ≥2). Time to first brigatinib dose reduction was not related to exposure. These results support the benefit‐risk profile of first‐line brigatinib 180 mg once daily (7‐day lead‐in dose at 90 mg once daily) in patients with ALK+ NSCLC.
Haemoperitoneum associated with bilateral granulosa cell tumours in a pregnant mare treated by standing ovariectomy
Authors: Sinovich M. , Archer D. C. , Kane‐Smyth J. , Scarabelli S. , Ritchie A. , Kelly P. G.
Published: January 2022

This report describes the likely development and growth of bilateral granulosa cell tumours (GCTs) in a Warmblood pony mare, during the first trimester of pregnancy after artificial insemination. The GCTs were initially suspected to be ovarian haematomas and were managed conservatively. However, they ultimately led to life‐threatening haemoperitoneum (HP) and were later diagnosed as GCTs with histopathology. The case was successfully managed with emergency standing laparoscopic‐assisted bilateral ovariectomy after haemodynamic supportive therapy. The mare made a full recovery and delivered a live filly foal at term. GCTs can be a rare cause of life‐threatening HP and can be successfully managed with haemodynamic support and standing laparoscopic‐assisted removal. Bilateral ovariectomy in a pregnant mare after 70 days of gestation can result in successful delivery of a live foal.
Patient‐reported outcomes in autosomal inherited bleeding disorders: A systematic literature review
Authors: van Hoorn Evelien S. , Houwing Maite E. , Al Arashi Wala , Leebeek Frank W. G. , Hazelzet Jan A. , Gouw Samantha C. , Schutgens Roger E. G. , Schols Saskia E. M. , Lingsma Hester F. , Cnossen Marjon H. ,   the SYMPHONY consortium
Published: January 2022

Aim

Currently, it is unknown which patient‐reported outcomes are important for patients with autosomal inherited bleeding disorders. Therefore, the purpose of this study is to systematically review the available literature assessing patient‐reported outcomes and their measurement methods in autosomal inherited bleeding disorders.

Methods

The Embase, Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trails and Google Scholar databases were searched from inception until 14 August 2020. Studies on patient‐reported outcomes in patients with von Willebrand disease, inherited platelet function disorders and coagulation factor deficiencies were included.

Results

Twenty‐one articles met the inclusion criteria. Three studies were assessed as having poor quality, and therefore a high risk of bias. Nineteen studies had fair quality rating. Different measurements methods were used, ranging from predefined to self‐developed questionnaires. The majority of included studies focused on von Willebrand disease. Patients with von Willebrand disease reported lower health‐related quality of life compared to the general population. Overall, this trend was especially visible in the following domains: vitality, physical and social functioning and pain. Women with inherited bleeding disorders scored lower on health‐related quality of life compared to men, especially women with heavy menstrual bleeding. Patients with joint bleeds or heavy menstrual bleeding reported an increased level of pain.

Conclusion

Patients with autosomal inherited bleeding disorders report lower health related quality of life, especially those with joint bleeds or heavy menstrual bleeding. Numerous measurement methods are used in patients with autosomal inherited bleeding disorders, highlighting the need for studies using established, standardized measurement methods.
Upregulation of the novel lncRNA U731166 is associated with migration, invasion and vemurafenib resistance in melanoma
Authors: Siena Ádamo Davi Diógenes , Barros Isabela Ichihara de , Storti Camila Baldin , de Biagi Júnior Carlos Alberto Oliveira , da Costa Carvalho Larissa Anastacio , Maria‐Engler Silvya Stuchi , Sousa Josane de Freitas , Silva Wilson Araújo
Published: January 2022

Our previous work using a melanoma progression model composed of melanocytic cells (melanocytes, primary and metastatic melanoma samples) demonstrated various deregulated genes, including a few known lncRNAs. Further analysis was conducted to discover novel lncRNAs associated with melanoma, and candidates were prioritized for their potential association with invasiveness or other metastasis‐related processes. In this sense, we found the intergenic lncRNA U73166 (ENSG00000230454) and decided to explore its effects in melanoma. For that, we silenced the lncRNA U73166 expression using shRNAs in a melanoma cell line. Next, we experimentally investigated its functions and found that migration and invasion had significantly decreased in knockdown cells, indicating an essential association of lncRNA U73166 for cancer processes. Additionally, using naïve and vemurafenib‐resistant cell lines and data from a patient before and after resistance, we found that vemurafenib‐resistant samples had a higher expression of lncRNA U73166. Also, we retrieved data from the literature that indicates lncRNA U73166 may act as a mediator of RNA processing and cell invasion, probably inducing a more aggressive phenotype. Therefore, our results suggest a relevant role of lncRNA U73166 in metastasis development. We also pointed herein the lncRNA U73166 as a new possible biomarker or target to help overcome clinical vemurafenib resistance.
Application of 3D‐printed colored 3D‐models for the fabrication of full ceramic restorations: A technical report
Authors: Schweiger Josef , Güth Jan‐Frederik , Edelhoff Daniel , Seidel Kathrin , Graf Tobias
Published: January 2022

Objective

This paper presents a novel digital workflow that expedites and facilitates the manufacturing of high‐end full‐ceramic restorations based on “Print and Press”‐Technology combined with 3D‐printed colored 3D‐models.

Clinical considerations

Despite ongoing innovations and developments in the digital workflow, the precision, and the final esthetic outcome is still limited compared with conventional press ceramics. The proposed method combines the advantages of digital scan‐ and design technologies with the proven conventional press‐technology to accomplish high‐end full‐ceramic restorations. The restoration is digitally designed, the data set is 3D‐printed in resin that can be burned out, subsequently conventionally embedded and pressed. Final esthetic finishing of the partial restorations is done on a 3D‐printed physical colored 3D‐model.

Conclusion

The report describes synergetic effects of digital and analog procedures. 3D‐printed colored 3D‐models can positively support the manufacturing of full ceramic restorations regarding their optical integration. Therefore, the use of 3D‐printed colored 3D‐models signifies a new innovative technique with many promising application areas.

Clinical significance

The combination of excellent clinical long‐term data for pressed ceramic restorations and proven digital processes, like intraoral scanning, design, and additive manufacturing, in the dental field promise an individual workflow for predictability and excellent esthetics.
Effects of antipsychotics on intravenous sedation with midazolam and propofol during dental treatment for patients with intellectual disabilities
Authors: Oda Y. , Yoshida K. , Kawano R. , Yoshinaka T. , Oda A. , Takahashi T. , Oue K. , Mukai A. , Irifune M. , Okada Y.
Published: January 2022

Background

Some patients with intellectual disabilities (ID) are prescribed antipsychotic drugs for symptomatic treatment of behavioural disorders. Nevertheless, it can still prove difficult to perform dental treatments safely for some patients with ID. In such cases, treatment under intravenous sedation (IVS) is one option. Sedative, hypnotic and α‐blocking effects of antipsychotic drugs may cause adverse events, such as severe hypotension, among patients who take antipsychotic drugs regularly. This study aimed to investigate the effects of oral antipsychotic medication on cardiovascular function during IVS. Accordingly, we compared mean blood pressure (MBP) and heart rate (HR) between patients who regularly take antipsychotic drugs and patients who do not.

Methods

Thirty‐seven patients with ID were enrolled in this study. All participants were outpatients of Special Care Dentistry of general hospital and received dental treatment under IVS performed with a combination of midazolam and propofol. Eighteen patients regularly took antipsychotics (medication group), and 19 patients were not currently taking antipsychotics (non‐medication group). MBP, HR, dose, and effect‐site concentration of intravenous sedative medications were measured at three points: ‘before IVS’, ‘at optimal sedation’, and ‘during dental treatment’.

Results

The magnitude of reduction of MBP was significantly smaller in the medication group than in the non‐medication group (P < 0.023). However, there were no differences in MBP, HR, dose, and effect‐site concentration of midazolam and propofol between groups at any point.

Conclusion

These results suggest that antipsychotic medication may not have clinically significant adverse effects on cardiovascular fluctuations during dental treatment under IVS for persons with ID.
Role of miRNAs in melanin metabolism: Implications in melanin‐related diseases
Authors: Zhang Zhigang , Shen Wanlu , Liu Weimin , Lyu Lechun
Published: January 2022

Background

MicroRNAs (miRNAs) are short single‐stranded non‐coding RNAs that regulate degradation and expression of messenger RNA (mRNA) and play a wide range of key roles in different biological processes. They mediate different stages of melanocyte differentiation, growth, and apoptosis through a variety of pathways and can mediate melanin production by targeting key enzymes.

Aims

This article was aimed to review the role of miRNAs in melanin metabolism and to introduce the role and significance of miRNAs in melanin‐related diseases.

Materials & Methods

Systematic search and retrospective review were performed on the published data.

Results

This paper reviews the process of melanin synthesis and the regulatory mechanism, explores the miRNA expression profiles in different model organisms, and introduces the mechanisms of several key miRNAs participating in melanin metabolism through target genes. We also explore the potential role of miRNA as a new target for the treatment of melanin metabolism disease, including vitiligo, melanoma, and chloasma.

Conclusion

miRNAs play a key role in melanin‐related diseases, and the miRNAs involved may be potential therapeutic targets.
An ethylene‐responsive transcription factor and a flowering locus KH domain homologue jointly modulate photoperiodic flowering in chrysanthemum
Authors: Huang Yaoyao , Xing Xiaojuan , Tang Yun , Jin Jinyu , Ding Lian , Song Aiping , Chen Sumei , Chen Fadi , Jiang Jiafu , Fang Weimin
Published: January 2022

The timely transition from vegetative to reproductive development is coordinated through the quantitative regulation of floral pathway genes in response to physiological and environmental cues. The function of ethylene‐responsive element‐binding protein (ERF) transcription factors in the regulation of flowering in chrysanthemum (Chrysanthemum morifolium Ramat.) is not well understood. Here, chrysanthemum overexpressing CmERF110 flowered earlier than the wild‐type plants, while those in which CmERF110 was suppressed flowered later. RNA‐seq results revealed that several genes involved in the circadian rhythm were transcribed differently in CmERF110 transgenic plants from that of the wild‐type plants. The rhythm peak of the circadian clock genes in transgenic plants was delayed. Yeast two‐hybrid screening of CmERF110 interactors identified a chrysanthemum FLOWERING LOCUS KH DOMAIN (FLK) homologue CmFLK, which was further confirmed with both in vitro and in vivo assays. KEGG pathway enrichment also revealed that CmFLK is involved in the regulation of circadian rhythm‐related genes. CmFLK transgenic plants showed a change in flowering time and delayed rhythm peak of the circadian rhythm genes. Taken together, the present data not only suggest that CmERF110 interacts with CmFLK to promote floral transition by tuning the circadian clock, but also provides evidence for the evolutionary conservation of the components in the autonomous pathway in chrysanthemum.
The architecture of psychological well‐being: A network analysis study of the Ryff Psychological Well‐Being Scale
Authors: Blasco‐Belled Ana , Alsinet Carles
Published: January 2022

The proliferation of mental health research is orienting its efforts towards the exploration of psychological well‐being. One of the main burdens is the measurement challenges reported by the widely used Psychological Well‐Being Scale (PWBS), which has often been criticized for inconsistencies between the theoretical and the empirical model. A potential alternative to understand the structure of psychological well‐being is network models, which conceptualizes psychological phenomena as emerging systems of mutually connected variables. Employing exploratory graph analysis, we examined the network structure of the Spanish 29‐item PWBS in a random sample of 1,404 adults. We estimated a regularized partial correlation network using the graphical LASSO algorithm in the item and dimension level. We tested the stability of both networks and identified the most important variables of the network. The PWBS network model revealed four dimensions, with self‐acceptance, life purpose and environmental mastery clustering together. Node strength centrality suggested that self‐acceptance is the most central dimension in the psychological well‐being structure as measured by the PWBS. Despite the network model of psychological well‐being did not replicate the theoretical structure of Ryff's model, it provides a novel conceptualization of psychological well‐being and proposes target indicators for mental health interventions.
Coalescence of ultrathin films by atomic layer deposition or chemical vapor deposition: Models of the minimum thickness based on nucleation and growth rates
Authors: LaFollette Diana K. , Canova Kinsey L. , Zhang Zhejun V. , Abelson John R.
Published: January 2022

Ultrathin, pinhole-free, and atomically smooth films are essential for future development in microelectronic devices. However, film morphology and minimum thickness are compromised when growth begins with the formation of islands on the substrate, which is the case for atomic layer deposition or chemical vapor deposition (CVD) on relatively unreactive substrates. Film morphology at the point of coalescence is a function of several microscopic factors, which lead to measurable, macroscopic rates of island nucleation and growth. To quantify the effect of these rates on the morphology at the point of coalescence, we construct two models: (1) a Monte Carlo simulation generates the film height profile from spatially random nucleation events and a constant island growth rate; simulated films resemble AFM images of the physical films; (2) an analytical model uses Poisson point statistics to determine the film thickness required to cover the last bare site on the substrate as a function of the nucleation rate and growth rate. Both models predict the same maximum thickness required to reach 99% coverage and reveal a power law relationship between the maximum thickness and the ratio of the nucleation rate divided by the growth rate. The Monte Carlo simulation further shows that the roughness scales linearly with thickness at coverages below 100%. The results match well with experimental data for the low-temperature CVD of HfB2 on Al2O3 substrates, but there are significant discrepancies on SiO2 substrates, which indicate that additional surface mechanisms must play a role.
High current silicon nanowire field emitter arrays
Authors: Bachmann Michael , Düsberg Felix , Pahlke Andreas , Edler Simon , Schels Andreas , Herdl Florian , Ławrowski Robert , Schreiner Rupert
Published: January 2022

Arrays of n-doped silicon nanowire field emitters with a high aspect ratio are realized by a novel dry etching technique. Compared to the high current silicon emitters in the literature, the manufacturing process is much simpler and requires only a single photolithography step and two dry etching steps. The cathodes realized with this method exhibit a total current of 20 mA from an active area of 4×4 mm2, which is significantly higher than that for most known structures made from silicon and also represents good performance in comparison with other emitter types, e.g., carbon nanotubes. In addition to characterization in ultrahigh vacuum, measurements at 10−5 mbar are performed and compared with our recent silicon emitters. Compared to these cathodes, the structures with the nanowires exhibit at least two orders of magnitude higher current-carrying capability.
Semantic context and stimulus variability independently affect rapid adaptation to non-native English speech in young adults
Authors: Bieber Rebecca E. , Gordon-Salant Sandra
Published: January 2022

When speech is degraded or challenging to recognize, young adult listeners with normal hearing are able to quickly adapt, improving their recognition of the speech over a short period of time. This rapid adaptation is robust, but the factors influencing rate, magnitude, and generalization of improvement have not been fully described. Two factors of interest are lexico-semantic information and talker and accent variability; lexico-semantic information promotes perceptual learning for acoustically ambiguous speech, while talker and accent variability are beneficial for generalization of learning. In the present study, rate and magnitude of adaptation were measured for speech varying in level of semantic context, and in the type and number of talkers. Generalization of learning to an unfamiliar talker was also assessed. Results indicate that rate of rapid adaptation was slowed for semantically anomalous sentences, as compared to semantically intact or topic-grouped sentences; however, generalization was seen in the anomalous conditions. Magnitude of adaptation was greater for non-native as compared to native talker conditions, with no difference between single and multiple non-native talker conditions. These findings indicate that the previously documented benefit of lexical information in supporting rapid adaptation is not enhanced by the addition of supra-sentence context.
Physical Activity Leadership Development Through a Physical Education Teacher Education Service-Learning Course
Authors: Egan Cate A. , Merica Christopher B. , Goc Karp Grace , Orendorff Karie , Beth McKown Hayley
Published: January 2022

Purpose: The purpose of this study was to understand how a service-learning project implementation can help preservice physical education teachers develop physical activity (PA) leadership skills. Methods: A qualitative exploratory single case study was employed, and eight preservice physical education students enrolled in service-learning course were recruited. Data included pre/post self-assessment surveys, reflection journals, individual interviews, and final poster presentations, and were coded using service-learning as a lens. Trustworthiness was established using multiple strategies. Results: Three major themes emerged, each with their own subthemes. Theme 1 was Practical Experience, Theme 2 was Learning to be Leaders, and Theme 3 was Service-Learning. Discussion/Conclusion: The hands-on structure of a service-learning course allowed students to develop PA leadership skills and provided them with the skills and confidence needed to implement expanded PA programs in the future. Service-learning courses are a viable option for PA leadership training in teacher education programs.
Signaling by the tyrosine kinase Yes promotes liver cancer development
Authors: Guégan Jean-Philippe , Lapouge Marjorie , Voisin Laure , Saba-El-Leil Marc K. , Tanguay Pierre-Luc , Lévesque Kim , Brégeon Jérémy , Mes-Masson Anne-Marie , Lamarre Daniel , Haibe-Kains Benjamin , Trinh Vincent Q. , Soucy Geneviève , Bilodeau Marc , Meloche Sylvain
Published: January 2022

Most patients with hepatocellular carcinoma (HCC) are diagnosed at a late stage and have few therapeutic options and a poor prognosis. This is due to the lack of clearly defined underlying mechanisms or a dominant oncogene that can be targeted pharmacologically, unlike in other cancer types. Here, we report the identification of a previously uncharacterized oncogenic signaling pathway in HCC that is mediated by the tyrosine kinase Yes. Using genetic and pharmacological interventions in cellular and mouse models of HCC, we showed that Yes activity was necessary for HCC cell proliferation. Transgenic expression of activated Yes in mouse hepatocytes was sufficient to induce liver tumorigenesis. Yes phosphorylated the transcriptional coactivators YAP and TAZ (YAP/TAZ), promoting their nuclear accumulation and transcriptional activity in HCC cells and liver tumors. We also showed that YAP/TAZ were effectors of the Yes-dependent oncogenic transformation of hepatocytes. Src family kinase activation correlated with the tyrosine phosphorylation and nuclear localization of YAP in human HCC and was associated with increased tumor burden in mice. Specifically, high Yes activity predicted shorter overall survival in patients with HCC. Thus, our findings identify Yes as a potential therapeutic target in HCC.
Proteomic Correlates of Enhanced Daptomycin Activity following β-Lactam Preconditioning in Daptomycin-Resistant, Methicillin-Resistant Staphylococcus aureus
Authors: Lew Cassandra , Pellitteri Hahn Molly , Scarlett Cameron , Rottier Aaron , Berti Andrew D. , Proctor Richard A. , Bayer Arnold S. , Rose Warren E.
Published: January 2022

Clinical treatment options for daptomycin (DAP)-resistant (DAP-R), methicillin-resistant
Staphylococcus aureus
(MRSA) infections are relatively limited. Current therapeutic strategies often take advantage of potential synergistic activity of DAP plus β-lactams; however, the mechanisms underlying their combinatorial efficacy are likely complex and remain incompletely understood.
NovelADAMTSL4gene mutations in Chinese patients with isolated ectopia lentis
Authors: Guo Dongwei , Yang Fengmei , Zhou Yijing , Zhang Xinyu , Cao Qianzhong , Jin Guangming , Zheng Danying
Published: January 2022

Background

To characterise the phenotype and genetic defects of isolated ectopia lentis (IEL) and to determine theADAMTSL4gene mutation frequencies in a Chinese congenital ectopia lentis (CEL) cohort.

Methods

In total, 127 Chinese probands with a clinical CEL diagnosis were recruited for this study and underwent ocular and systemic examinations. Whole-exome sequencing was used to detect variants, and Sanger sequencing and bioinformatics analysis verified the pathogenic mutations.

Results

Overall, biallelic mutations inADAMTSL4,involving 8 novelADAMTSL4mutations (c.21–2A>G, c.1174G>C, c.2169C>A, c.2236C>T, c.2263delG, c.2397C>A, c.2488dupC and c.2935T>C) were identified in 5 probands (5/127, 3.94%) with IEL. Additionally, four patients had combined congenital cataracts, and two patients had ectopia lentis et pupillae (ELP). One of eight mutations was a homozygous missense mutation, and the other seven mutations were compound heterozygous. These eight consisted of three missense (37.5%), three frameshift (37.5%), one stop-gain (12.5%) and one spicing mutation (12.5%). These mutations co-segregated with the IEL, and the substitution of amino acids greatly affected conserved residues. Most of the novel mutations were located in the thrombospondin type 1 (TSP1) domain, which ultimately alters the structure of the ADAMTSL4 protein.

Conclusions

This study reported five IEL probands with eight novel mutations in theADAMTSL4gene. The clinical IEL phenotypes caused by these mutations were variable and complex. This study thus establishes theADAMTSL4gene mutation frequency and expands the gene’s mutation spectrum to help recogniseADAMTSL4-related IEL clinical manifestations.
Prevalence of common mental health disorders in military veterans: using primary healthcare data
Authors: Finnegan Alan , Randles R
Published: January 2022

Introduction

Serving military personnel and military veterans have been identified as having a high prevalence of mental disorders. Since 1985, UK patients’ primary healthcare (PHC) medical records contain Read Codes (now being replaced by Systematized Nomenclature of Medicine - Clinical Terms (SNOMED CT) codes) that mark characteristics such as diagnosis, ethnicity and therapeutic interventions. This English study accesses a cohort profile of British Armed Forces veterans to examine the diagnosed common mental disorders by using PHC records.

Methods

This analysis has been drawn from initiatives with PHC practices in the Northwest of England to increase veteran registration in general practice. Demographic data were collected including gender, age and marital status. Data were also collected on common mental health disorders associated with the Armed Forces.

Result

2449 veteran PHC records were analysed. 38% (N=938) of veterans in this cohort had a code on their medical record for common mental health disorders. The highest disorder prevalence was depression (17.8%, N=437), followed by alcohol misuse (17.3%, N=423) and anxiety (15.0%, N=367). Lower disorder prevalence was seen across post-traumatic stress disorder (PTSD) (3.4%, N=83), dementia (1.8%, N=45) and substance misuse (0.8%, N=19). Female veterans had a higher prevalence of mental disorders than their male counterparts, while men a higher prevalence of PTSD; however, the gender difference in the latter was not significant (p>0.05).

Conclusion

The SNOMED searches do not detail why certain groups had higher recordings of certain disorders. A future study that accesses the PHC written medical notes would prove enlightening to specifically identify what situational factors are having the most impact on the veteran population. The results from a sizeable English veteran population provide information that should be considered in developing veteran-specific clinical provision, educational syllabus and policy.
Use of the kidney failure risk equation to inform clinical care of patients with chronic kidney disease: a mixed-methods systematic review
Authors: Bhachu Harjeet Kaur , Fenton Anthony , Cockwell Paul , Aiyegbusi Olalekan , Kyte Derek , Calvert Melanie
Published: January 2022

Rationale and objective

The Kidney Failure Risk Equation (KFRE) predicts the risk of end-stage kidney disease in patients with chronic kidney disease (CKD). This study aimed to evaluate the impact of the utility of KFRE in clinical practice.

Study design

Systematic review.

Setting and study populations

Adult patients with CKD but not receiving renal replacement therapy enrolled in studies where KFRE was used in clinical care pathways.

Selection criteria for studies

All studies published from April 2011 to October 2021 identified from Medline, Cumulative Index to Nursing and Allied Health Literature, Embase and reference and citation searches of included studies.

Data extraction

Relevant data were extracted, and two reviewers independently assessed study quality using appropriate appraisal tools.

Analytical approach

Findings reported as a narrative synthesis due to heterogeneity of the included studies.

Results

Of 1635 studies identified, 440 duplicates were removed. The remaining 1195 titles and abstracts were screened. All five studies for full-text review were included in the analysis. Three uses of KFRE were assessed: (1) primary to specialty care interface; (2) general nephrology to multidisciplinary care transition; and (3) treatment planning. Evidence of impact on number of patient referrals into nephrology care was conflicting. However, wait times improved in one study. Although KFRE identified high-risk patients for increased multidisciplinary support, there was concern patients stepped down, no longer meeting eligibility criteria, may lack access to services.

Conclusions

This is the first systematic review of studies that have assessed the actual impact of KFRE in clinical practice with five studies of varying quality reported to date. Trials are in progress assessing the impact on clinical outcomes of using KFRE in clinical practice, and KFRE is being incorporated into guidelines for CKD management. Further studies are needed to assess the impact of KFRE on clinical care.

Trial registration number

Protocol registered on PROSPERO before initiation of the study (Ref: CRD42020219926).
Integration of rapid PCR testing as an adjunct to NGS in diagnostic pathology services within the UK: evidence from a case series of non-squamous, non-small cell lung cancer (NSCLC) patients with follow-up
Authors: Finall Alison , Davies Gareth , Jones Trevor , Emlyn Gwion , Huey Pearl , Mullard Anna
Published: January 2022

Aims

Somatic genetic testing in non-squamous, non-small cell lung carcinoma (NSCLC) patients is required to highlight subgroups eligible for a number of novel oncological therapies. This study aims to determine whether turnaround times for reporting epidermal growth factor receptors (EGFR) by next-generation sequencing (NGS) alone is sufficient to meet the needs of lung cancer patients.

Methods

We performed a retrospective case series with follow-up. Outcomes of EGFR testing (102 tests) in 96 patients by NGS were compared with a rapid, fully automated PCR-based platform (Idylla) in local histopathology laboratories.

Results

Turnaround time for reporting NGS was 17 calendar days. Reporting using the Idylla EGFR Mutation Test, by contrast, gave a potential turnaround time of 3.8 days from request to authorisation. Three-quarters of patients presenting with stage IV disease had a performance status of 0, 1, or 2 but 18% experienced rapid clinical deterioration (p<0.05). A third of these patients were deceased by the time NGS reports were available.

Conclusions

We discuss issues around integrating rapid PCR testing alongside NGS in multidisciplinary care pathways and strategies for mitigating against foreseeable difficulties. Dual testing for stage IV non-squamous, NSCLC patients has the potential to improve care and survival outcomes by providing access to the right test at the right time.
Evaluation of long-term TNFi effectiveness after a first switch in early axial spondyloarthritis considering time-varying prescription bias: an inverse-probability weighting analysis of the DESIR cohort
Authors: Pons Marion , Chevret Sylvie , Briot Karine , d’Agostino Maria-Antonietta , Roux Christian , Dougados Maxime , Molto Anna
Published: January 2022

Objective

To evaluate long-term effectiveness of tumour necrosis factor inhibitor (TNFi) after a first switch, and their associated factors in an early axial spondyloarthritis (axSpA) population, considering time-varying prescription bias.

Methods

Observational prospective cohort (DEvenir des Spondylarthropathies Indifférenciées Récentes) with 5 years of follow-up, including 708 TNFi-naïve patients with early axSpA. Long-term effectiveness of TNFi after a first switch (ASAS40 response after at least 2 visits under treatment) were estimated using marginal structural models (implementing inverse-probability weighting and iterative propensity scores). Factors associated with the outcome were explored by multivariate Cox regression models.

Results

The hazard to present an ASAS40 response after a first TNFi switch was increased (HR=2.4 (95% CI 1.9 to 3.0)); this response ratio was slightly lower compared with the response in TNFi naïve patients after a first TNFi (HR=3.3 (95% CI 2.9 to 3.8)). HLA-B27 positive was the only factor independently associated with ASAS40 response after a first TNFi switch.

Conclusion

After application of innovative methods to overcome time-varying prescription bias, the magnitude of the TNFi response after a first switch was found to be numerically lower but clinically relevant from the response in TNFi-naïve patients.
Comprehensive assessment of multimorbidity burden in a population-based cohort of patients with rheumatoid arthritis
Authors: Crowson Cynthia S , Gunderson Tina M , Dykhoff Hayley J , Myasoedova Elena , Atkinson Elizabeth J , Kronzer Vanessa L , Coffey Caitrin M , Davis III John M
Published: January 2022

Objective

To comprehensively assess multimorbidity burden in patients with rheumatoid arthritis (RA) in order to unify the multimorbidity definition for RA research and clinical practice.

Methods

In this population-based study, residents of eight Minnesota counties with prevalent RA on 1 January 2015 were identified. Age, sex and county-matched non-RA comparators were selected from the same population. Diagnostic codes were retrieved for 5 years before 1 January 2015. Using two codes ≥30 days apart, 44 previously defined morbidities and 78 non-overlapping chronic disease categories based on Clinical Classification Software were defined. Prevalence of each morbidity in the RA versus non-RA cohorts was compared using false discovery rate to adjust for multiple comparisons. Morbidities more common in RA than non-RA and those with prevalence ≥5% were retained.

Results

1643 patients with RA and 1643 non-RA subjects (72% women; mean age 63.1 years) were studied. Using the 44 morbidities, multimorbidity (defined as 2+ morbidities) was present in 1411 (86%) of RA and 1164 (71%) of non-RA subjects (p<0.001) with 5+ morbidities present in 907 (55%) of RA and 619 (38%) of non-RA (p<0.001). Patients with RA had significantly higher prevalence of 24 of the 44 morbidities compared with non-RA, especially interstitial lung disease, fibromyalgia, osteoarthritis and osteoporosis. Among the additional 78 categories, 7 were significantly higher in RA than non-RA, including organic sleep disorders, vitamin D deficiency and foot ulcers.

Conclusion

Patients with RA have a higher prevalence of multimorbidity compared with non-RA subjects. These results confirm the list of 44 morbidities and add several other morbidities of interest in RA.
Effects of biochar source, level of inclusion, and particle size on in vitro dry matter disappearance, total gas, and methane production and ruminal fermentation parameters in a barley silage-based diet
Authors: Tamayao Paul , Ribeiro Gabriel O. , McAllister Tim A. , Ominski Kim H. , Okine Erasmus K. , McGeough Emma J.
Published: January 2022

This study evaluated the effects of biochar differing in source, inclusion level, and particle size on dry matter disappearance (DMD), total gas and methane (CH4) production, and ruminal fermentation in a barley silage-based diet. The seven biochar products used were coconut (CP001 and CP014) or pine (CP002, CP015, CP016, CP023, CP024)-based. Experiment 1 (Exp. 1) evaluated these biochars at 4.5%, 13.5%, and 22.5% level of diet inclusion, whereas Experiment 2 (Exp. 2) evaluated CP002, CP016, and CP023 at 2.25% and 4.50% of the diet at <0.5, 0.5–2.0, >2.0 mm particle size. Data were analyzed using PROC MIXED in SAS as a randomized complete block design, with biochar source, inclusion level, and particle size (Exp. 2 only) as fixed effects with run and replicate as random effects. Increasing level of biochar inclusion linearly (P < 0.01) decreased DMD in Exp. 1 and did not influence DMD (P > 0.05) in Exp. 2. Total gas, CH4 (mL·g−1 DMD), and ruminal fermentation parameters were not affected by product, inclusion level, or particle size (P > 0.05). In conclusion, biochar of varying source and particle size did not mitigate CH4 production, but reduced DMD at higher inclusion levels in the barley silage-based diet.
Reference values for germination and emergence measurements
Authors: Ferreira Wanessa Resende , Ranal Marli A. , Santana Denise Garcia
Published: January 2022

Why should we care about reference values for germination and emergence measurements? Because they can help in the conservation of species and thus the recovery or restoration of altered areas. Therefore, for the first time, we evaluated the germination and emergence processes of diaspores of five Cerrado species to propose reference values for the germination and emergence measurements to enable species comparison, and consequently, facilitate better conservation decisions. The five species have diaspores with high physiological quality and intraspecific variability in relation to most of the germination and emergence measurements, showing that they still retain their reproductive potential. The processes of seed germination and seedling emergence in Anadenanthera colubrina (Vell.) Brenan and Ceiba speciosa (A.St.-Hil.) Ravenna and seedling emergence in Astronium urundeuva Engl. were faster and more synchronised than those of Cedrela fissilis Vell. (emergence) and Lithraea molleoides (Vell.) Engl. (germination and emergence), indicating the presence of dormancy in the diaspores of the last two species. However, considering the reference values determined here, all the species could be considered very slow and very asynchronous. This means that all the species use large environmental windows to establish themselves, where the spreading of seed germination and seedling emergence over time is an important survival advantage.
AAC McRae soybean
Authors: Yu K. , Woodrow L. , Shi C.
Published: January 2022

AAC McRae is a high yielding food grade soybean [Glycine max (L.) Merr.] cultivar with yellow hilum, high protein concentration, and acceptable processing quality for foreign and domestic tofu, soymilk, and miso markets. It has excellent soybean cyst nematode (SCN) (Heterodera glycines Ichinohe) and soybean sudden death syndrome (SDS) (Fusarium virguliforme O'Donnell & T. Aoki) resistance. AAC McRae was developed at the Agriculture and Agri-Food Canada (AAFC) Harrow Research and Development Centre (Harrow-RDC), Harrow, Ontario, and is adapted to areas of southwest Ontario with 3100 or more crop heat units and has a relative maturity group of 2.2 (MG 2.2).
Universal transcendentality limit of BFKL eigenvalue
Authors: Joubat Mohammad , Prygarin Alex
Published: January 2022

We consider a special limit of the BFKL eigenvalue at $$\nu \rightarrow 0$$

ν
→
0

and odd values of the conformal spin n. We show that in this limit the NLO BFKL eigenvalue can be expressed in terms of a limited set of transcendental constants with rational coefficients. We show that the leading transcendentality term in this limit is universal and does not depend on a specific value of n.