bluuebunny/crossref_metadata_2025 huggingface dataset:
Secukinumab as a potential trigger of inflammatory bowel disease in ankylosing spondylitis or psoriatic arthritis patients
Authors: Onac Ioana A , Clarke Benjamin D , Tacu Cristina , Lloyd Mark , Hajela Vijay , Batty Thomas , Thoroughgood Jamie , Smith Sandra , Irvine Hannah , Hill Diane , Baxter Grace , Horwood Natalie , Mahendrakar Suma , Rajak Rizwan , Griffith Sian , Kiely Patrick D W , Galloway James
Published: February 2021

Objective

Real-world secukinumab gastrointestinal-related adverse events (GIRAE) data during treatment for AS and PsA are lacking. We aimed to obtain this through baseline evaluation of pre-existing IBD rates and predictors of GIRAE.

Methods

Patient electronic and paper records commencing secukinumab from 10 UK hospitals between 2016 and 2019 were reviewed. GIRAE after initiation were defined as: definite [objective evidence of IBD (biopsy proven), clear temporal association, resolution of symptoms on drug withdrawal, no alternative explanation felt more likely], probable (as per definite, but without biopsy confirmation) or possible (gastrointestinal symptoms not fulfilling definite or probable criteria).

Results

Data for all 306 patients started on secukinumab were analysed: 124 (40.5%) AS and 182 (59.5%) PsA. Twenty-four of 306 (7.8%) experienced GIRAE after starting secukinumab. Amongst patients who developed GIRAE, four (1.3%) had definite, seven (2.3%) probable and 13 (4.2%) possible IBD. All definite cases were patients with AS and stopped secukinumab; two had pre-existing IBD and two (0.7%) were de novo cases of which one required surgical intervention. Seven patients (2.3%) had pre-existing diagnoses of IBD prior to initiation, of which five patients experienced GIRAE.

Conclusion

Absolute rates of new IBD in patients starting secukinumab are low. The majority of patients developing new GIRAE did not develop objective evidence of IBD or stop therapy. For patients with pre-existing IBD and AS the risk of GIRAE is much higher, and prescribing alternatives should be considered.
Risk Factors for Klebsiella infections among hospitalized patients with Pre-Existing Colonization
Authors: Rao Krishna , Patel Alieysa , Sun Yuang , Vornhagen Jay , Motyka Jonathan , Collingwood Abigail , Teodorescu Alexandra , Zhao Lili , Kaye Keith S. , Bachman Michael
Published: February 2021

Background

Klebsiella commonly colonizes the intestinal tract of hospitalized patients and is a leading cause of healthcare-associated infections. Colonization is associated with subsequent infection, but the factors determining this progression are unclear.

Methods

Intensive care and hematology/oncology patients were screened for Klebsiella colonization by rectal swab culture and monitored for infection for 90 days after a positive swab. Electronic medical records were analyzed for patient factors associated with subsequent infection, and variables of potential significance in bivariable analysis were used to build a final multivariable model. Concordance between colonizing and infecting isolates was assessed by wzi capsular gene sequencing.

Results

Among 2087 hospital encounters from 1978 colonized patients, 90 cases of infection (4.3%) were identified. Mean time to infection was 20.6 ±24.69 (range 0-91, median 11.5) days. Of 86 typed cases, 68 unique wzi types were identified and 69 cases (80.2%) were colonized with an isolate of the same type prior to infection. Based on multivariable modeling, overall comorbidities, depression and low albumin level at the time of rectal swab were independently associated with subsequent Klebsiella infection.

Conclusions

Despite the high diversity of colonizing strains of Klebsiella, there is high concordance with subsequent infecting isolates and progression to infection is relatively quick. Readily accessible data from the medical record could be used by clinicians to identify colonized patients at increased risk of subsequent Klebsiella infection.

Importance

Klebsiella is a leading cause of healthcare-associated infections. Patients who are intestinally colonized with Klebsiella are at significantly increased risk of subsequent infection, but only a subset of colonized patients progress to disease. Colonization offers a potential window of opportunity to intervene and prevent these infections, if the patients at greatest risk could be identified. To identify patient factors associated with infection in colonized patients, we studied 1978 colonized patients. We found that patients with a higher burden of underlying disease in general, depression in particular, and low albumin in a blood test were more likely to be a case of infection. However, these variables did not completely predict infection, suggesting that other host and microbial factors may also be important. The average time to infection was 3 weeks, suggesting that there is time to intervene and prevent Klebsiella infections in hospitalized patients.
TheParastagonospora nodorumnecrotrophic effector SnTox5 targets the wheat geneSnn5and facilitates entry into the leaf mesophyll
Authors: Kariyawasam Gayan K. , Richards Jonathan K. , Wyatt Nathan A. , Running Katherine , Xu Steven S. , Liu Zhaohui , Borowicz Pawel , Faris Justin D. , Friesen Timothy L.
Published: February 2021

Parastagonospora nodorum, causal agent of septoria nodorum blotch, is a destructive necrotrophic fungal pathogen of wheat.P. nodorumis known to secrete several necrotrophic effectors that target wheat susceptibility genes that trigger classical biotrophic resistance responses but resulting in susceptibility rather than resistance. SnTox5 targets the wheat susceptibility geneSnn5to induce necrosis. In this study, we used full genome sequences of 197P. nodorumisolates collected from the US and their disease phenotyping on theSnn5differential line LP29, to perform genome wide association study analysis to localize theSnTox5gene to chromosome 8 ofP. nodorum.SnTox5was validated using gene transformation and CRISPR-Cas9 based gene disruption.SnTox5encoded a small secreted protein with a 22 and 45 amino acid secretion signal and a pro sequence, respectively. TheSnTox5gene is under purifying selection in the Upper Midwest but under strong diversifying selection in the South/East regions of the US. Comparison of wild type and SnTox5-disrupted strains on wheat lines with and without the susceptibility targetSnn5showed that SnTox5 has two functions, 1) facilitating colonization of the mesophyll layer, and 2) targeting Snn5 to induce programmed cell death to provide cellular nutrient to complete its necrotrophic life cycle.
Evaluation of the growth performance, physiological traits, antioxidant indices, and heat shock protein 70 to dietary supplementation of stinging nettle (Urtica dioica) in broilers exposed to chronic heat stress
Authors: Farahani Mehrad Mirsaiidi , Hosseinian Seyedeh Alemeh
Published: February 2021

Heat stress is known as one of the most prevalent environmental stressors in poultry production, which is associated with oxidative stress. Stinging nettle is a medicinal herb with strong antioxidant properties. The present study was conducted to evaluate the effects of dietary stinging nettle at two different levels (2% and 4%) on growth performance and oxidative stress indices of broilers exposed to chronic heat stress. On day 14, a total of 240 broiler chickens were randomly assigned to 6 treatment groups as follows: 1) NC: negative control; 2) HS: heat-stressed broiler; 3) HS-SN2: heat-stressed broiler fed by 2% dietary stinging nettle; 4) HS-SN4: heat-stressed broilers fed by 4% stinging nettle; 5) SN2: no heat-stressed broilers fed by 2% dietary stinging nettle; 6) SN4: no heat-stressed broilers fed by 4% dietary stinging nettle. Diet supplementation with stinging nettle was performed from days 14 to 35 and a chronic heat stress was induced from days 22 to 29. The growth performance and oxidative indices were evaluated on days 14, 21, 29, and 35. Rectal temperature and panting frequency were assessed on days 22, 25, and 29. As a result, weight gain and food intake decreased in the HS compared to the NC, and these parameters increased in the HS-SN2 and HS-SN4 compared to the HS (P<0.05). The HS, HS-SN2, and HS-SN4 groups had a significantly higher rectal temperature and panting frequency. The HS had the higher circulating MDA and HSP70, and lower T-AOC, SOD, and GSH-Px compared to the treatments. The HS-SN4 had a significantly lower MDA and HSP70, and higher T-AOC, GSH-Px, and SOD compared to the HS and HS-SN2. In conclusion, the addition of 4% stinging nettle powder to the broilers’ diet improved the oxidative status in heat-stressed birds. Furthermore, this herb could be utilized as a feed additive in poultry diet to improve bird’s health and defense mechanisms under stressful conditions.
Single-cell analysis identifies a key role forHhipin murine coronal suture development
Authors: Holmes Greg , Gonzalez-Reiche Ana S. , Saturne Madrikha , Zhou Xianxiao , Borges Ana C. , Shewale Bhavana , Zhang Bin , van Bakel Harm , Jabs Ethylin Wang
Published: February 2021

Craniofacial development depends on proper formation and maintenance of sutures between adjacent bones of the skull. In sutures, bone growth occurs at the edge of each bone, and suture mesenchyme maintains the separation between them. We performed single-cell RNA-seq analyses of the embryonic, murine coronal suture. Analyzing replicate libraries at E16.5 and E18.5, we identified 14 cell populations. Seven populations at E16.5 and nine at E18.5 comprised the suture mesenchyme, osteogenic cells, and associated populations. Through an integrated analysis with bulk RNA-seq data, we found a distinct coronal suture mesenchyme population compared to other neurocranial sutures, marked by expression ofHhip, an inhibitor of hedgehog signaling. We found that at E18.5,Hhip-/-coronal osteogenic fronts are closely apposed and suture mesenchyme is depleted, demonstrating thatHhipis required for coronal suture development. Our transcriptomic approach provides a rich resource for insight into normal and abnormal development.
Chromatin and transcriptomic profiling uncover dysregulation of the Tip60 HAT/HDAC2 epigenomic landscape in the neurodegenerative brain
Authors: Beaver Mariah , Karisetty Bhanu Chandra , Zhang Haolin , Bhatnagar Akanksha , Armour Ellen , Parmar Visha , Brown Reshma , Xiang Merry , Elefant Felice
Published: February 2021

Disruption of histone acetylation mediated gene control is a critical step in Alzheimer’s Disease (AD), yet chromatin analysis of antagonistic histone acetyltransferases (HATs) and histone deacetylases (HDACs) causing these alterations remains uncharacterized. We report the first Tip60 HAT versus HDAC2 chromatin and transcriptional profiling study inDrosophilabrains that model early human AD. We find Tip60 and HDAC2 predominantly recruited to identical neuronal genes. Moreover, AD brains exhibit robust genome-wide early alterations that include enhanced HDAC2 and reduced Tip60 binding and transcriptional dysregulation. Orthologous human genes to co-Tip60/HDAC2Drosophilaneural targets exhibit conserved disruption patterns in AD patient hippocampi. Notably, we discovered distinct transcription factor (TF) binding sites within Tip60/HDAC2 co-peaks in neuronal genes, implicating them in co-enzyme recruitment. Increased Tip60 protects against transcriptional dysregulation and enhanced HDAC2 enrichment genome-wide. We advocate Tip60 HAT/HDAC2 mediated epigenetic neuronal gene disruption as a genome-wide initial causal event in AD.
A synthetic RNA-mediated evolution system in yeast
Authors: Jensen Emil D. , Laloux Marcos , Lehka Beata J. , Pedersen Lasse E. , Jakočiūnas Tadas , Jensen Michael K. , Keasling Jay D.
Published: February 2021

Laboratory evolution is a powerful approach to search for genetic adaptations to new or improved phenotypes, yet either relies on labour-intensive human-guided iterative rounds of mutagenesis and selection, or prolonged adaptation regimes based on naturally evolving cell populations. Here we present CRISPR- and RNA-assistedin vivodirected evolution (CRAIDE) of genomic loci using evolving chimeric donor gRNAs continuously delivered from an error-prone T7 RNA polymerase, and directly introduced as RNA repair donors into genomic targets under either Cas9 or dCas9 guidance. We validate CRAIDE by evolving novel functional variants of an auxotrophic marker gene, and by conferring resistance to a toxic amino acid analogue in baker’s yeastSaccharomyces cerevisiaewith a mutation rate >3,000-fold higher compared to spontaneous native rate, thus enabling the first demonstrations ofin vivodelivery and information transfer from long evolving RNA donor templates into genomic context without the use ofin vitrosupplied and pre-programmed repair donors.
The scaffold-dependent function of RIPK1 in dendritic cells promotes injury-induced colitis
Authors: Moriwaki Kenta , Park Christa , Koyama Kazuha , Balaji Sakthi , Kita Kohei , Yagi Ryoko , Komazawa-Sakon Sachiko , Asuka Tatsuya , Nakano Hiroyasu , Kamada Yoshihiro , Miyoshi Eiji , Chan Francis K.M.
Published: February 2021

Receptor interacting protein kinase 1 (RIPK1) is a cytosolic multidomain protein that controls cell life and death. While RIPK1 promotes cell death through its kinase activity, it also functions as a scaffold protein to promote cell survival by inhibiting FADD-caspase 8-dependent apoptosis and RIPK3-MLKL-dependent necroptosis. This pro-survival function is highlighted by excess cell death and a perinatal lethality inRipk1−/−mice. Recently, loss of function mutation ofRIPK1was found in patients with immunodeficiency and inflammatory bowel diseases. Hematopoietic stem cell transplantation restored not only immunodeficiency but also intestinal inflammatory pathology, indicating that RIPK1 in hematopoietic cells is critical to maintain intestinal immune homeostasis. Here, we generated dendritic cell (DC)-specificRipk1−/−mice in a genetic background with loss of RIPK1 kinase activity and found that the mice developed spontaneous colonic inflammation characterized by increased neutrophil infiltration. In addition, these mice were highly resistant to injury-induced colitis. The increased neutrophil infiltration in the colon and the resistance to colitis were restored by dual inactivation of RIPK3 and FADD, but not by inhibition of RIPK3, MLKL, or ZBP1 alone. Altogether, these results reveal a scaffold activity-dependent role of RIPK1 in protecting colonic DCs from apoptotic insults and maintenance of colonic immune homeostasis.
A partially sex-reversed giant kelp sheds light into the mechanisms of sexual differentiation in a UV sexual system
Authors: Müller Dieter G. , Gaschet Enora , Godfroy Olivier , Gueno Josselin , Cossard Guillaume , Kunert Maritta , Peters Akira F. , Westermeier Renato , Boland Wilhelm , Cock J. Mark , Lipinska Agnieszka P. , Coelho Susana M.
Published: February 2021

In UV sexual systems, sex is determined during the haploid phase of the life cycle and males have a V chromosome whereas females have a U chromosome. Previous work in the brown algal modelEctocarpusrevealed that the V chromosome has a dominant role in male sex determination and suggested that the female developmental program may occur by ‘default’, triggered in the absence of the male master sex determination gene(s). Here, we describe the identification of a genetically male giant kelp strain presenting phenotypic features typical of a female, despite lacking the U-specific region. The conversion to the female developmental program is however incomplete, because gametes of this feminised male are unable to produce the sperm-attracting pheromone lamoxirene. We identify the transcriptomic patterns underlying the male and female specific developmental programs, and reveal the faster evolutionary rates of male-biased genes compared to female-biased and unbiased genes. Moreover, we show that the phenotypic feminisation of the variant strain is associated with both feminisation and de-masculinisation of gene expression patterns. Importantly, the feminisation phenotype was associated with the dramatic downregulation of two V-specific genes including a candidate sex-determining gene on the V-specific region. Our results reveal the transcriptional changes associated with sexual differentiation in a UV system with marked sexual dimorphism, and contribute to disentangling the role of sex-linked genes and autosomal gene expression in the initiation of the male and female developmental programs. Overall, the data presented here imply that the U-specific region in the giant kelp is not required to initiate the female developmental program, but is critical to produce fully functional eggs, arguing against the idea that female is the ‘default’ sex in this species.
Employer brand to leverage employees’ intention to stay through sequential mediation model: evidence from Indian power sector
Authors: Rai Alka , Nandy Benjamin
Published: February 2021

Purpose

This study aims to explain the linkage between employer branding and employee retention; a sequential mediation is hypothesized, where it is proposed that the relationship between employer branding and employee retention is sequentially mediated by person–organization fit (P-O fit) and organizational identification.

Design/methodology/approach

The sample belongs to 224 executive-level employees of the Indian power sector organization. The sequential mediation model is tested by using SPSS macro command of Preacher and Hayes.

Findings

The findings established that the relationship between employer brand and employees’ intention to stay is sequentially mediated by P-O fit and organizational identification.

Practical implications

The findings emphasize the role of employer brand on constructs such as P-O fit, organizational identification and intention to stay. In addition, the established mechanism emphasizes the role of P-O fit to realize the benefits such as organizational identification and employee retention.

Originality/value

Internal branding efforts may have a major impact on workforce attitude and behavior including engagement, job performance and retention. “Yet studies of the positive impact of employer brand on employee attitudes and behaviors, or of the factors that shape employer brand, are rare” (Charbonnier-Voirin et al., 2017, p. 2). Along the line of such gap, this study has taken up to test the unexplored sequential mediation mechanism between employer brand and employees’ intention to stay through P-O fit and organizational identification.
The voice of dwellers – developing a place brand by listening to its residents
Authors: Hakala Ulla
Published: February 2021

Purpose

Listening to the customers has long been a key phrase and success element in product branding. This paper aims to highlight the importance of listening to residents during the branding of a place. The study explores ways of listening to residents to ensure they are heard and also discusses the challenges and benefits related to place branding flowing from having residents participate in decision-making processes.

Design/methodology/approach

Listening to residents and offering opportunities to participate requires place branders to fully attend to, comprehend and respond to residents’ comments, requests, ideas and feedback. This study reports on how two Nordic cities – Turku and Helsinki – listen to their residents. The data used comprise face-to-face interviews, telephone and e-mail conversations and documentary material.

Findings

Residents should not be considered as one homogeneous target; participation options and channels should be adapted to the demographics and geographic issues of the different regions and resident groups.

Research limitations/implications

The role of residents and the importance of listening are crucial features in the emerging concept of inclusive place branding (Kavaratziset al., 2017); its future conceptual development could benefit from the case examples at hand.

Practical implications

City authorities should listen to residents and provide them with opportunities to actively contribute to decision-making. Other cities could learn from the examples introduced in the paper.

Originality/value

This paper documents two Nordic examples of cities putting into practice a policy of listening to the residents, a previously neglected research area.
We were never cool: Investigating knowledge production and discourses of cool in the sociology of music
Authors: Haynes Jo , Nowak Raphaël
Published: February 2021

This article examines knowledge production in the sociology of music. Focusing on the idea of cool music, we interrogate the nature of music researchers' relationship with their object of research. While the qualification and connotation of cool is widespread in popular music, sociology has largely neglected to engage with it as an object of research. Instead, the sociological investigation of music audiences is divided between two opposed but co‐constructed paradigms that ultimately do not account for how cool emerges as a qualifier and connotation, how it performs as a discourse on music, and to what effect. Using the example of aging music researchers as a departure point, we examine how the cool connotations of music function as a mode of discourse that legitimates particular knowledge, practice, and taste, demarcating insider/outsider status. We explore how music acquires social connotations such as “cool” and whether that alters music researchers' approaches to it. We argue that apart from the disclosure of inclinations, social characteristics, and relationships to the object of research (music scenes, preferences, fandom, and so on), the tradition of reflexive empirical perspectives in music sociology should incorporate further deconstruction of the transformative dimensions in the relations between music and researcher. Music, as a complex and dynamic object, thus, requires sociology to produce accounts that both encompass people's enjoyment and experience as well as its boundary‐defining capacity.
Orofacial granulomatosis: Clinical and therapeutic features in an Italian cohort and review of the literature
Authors: Galdiero Maria R. , Maio Filomena , Arcoleo Francesco , Boni Elisa , Bonzano Laura , Brussino Luisa , Cancian Mauro , Cremonte Luigi , Del Giacco Stefano R. , De Paulis Amato , Detoraki Aikaterini , Firinu Davide , Lamacchia Donatella , Loffredo Stefania , Nettis Eustachio , Parente Roberta , Parronchi Paola , Pellacani Giovanni , Petraroli Angelica , Rolla Giovanni , Senter Riccardo , Triggiani Massimo , Vitiello Gianfranco , Spadaro Giuseppe , Bova Maria
Published: February 2021

Background

Orofacial granulomatosis (OFG) is characterized by granulomatous inflammation of the soft tissues of maxillofacial region. We explored OFG patients from 10 different Italian centers and summarized the most recent literature data.

Methods

A review of patients with OFG was carried out. An extensive online literature search was performed to identify studies reporting diagnosis and management of OFG.

Results

Thirty‐nine patients were recruited between January 2018 and February 2020. Most of them (97.4%) displayed involvement of the lips, and 28.2% suffered from Melkersson‐Rosenthal syndrome. Two patients received diagnosis of CD and one patient of sarcoidosis, suggesting secondary OFG. Oral aphthosis and cervical lymphadenopathy were also described. The mean diagnostic delay was 3.4 years. Histological evaluation was performed in 34/39 patients (87.2%); non‐caseating granulomas were found in 73.5% of them. Neurological symptoms (28.2%), gastrointestinal symptoms in absence of overt inflammatory bowel disease (IBD) (20.5%), and atopy (35.9%) were also identified. Therapeutic approaches varied among the centers. Steroids (51.3%) were used with good or partial results. Anti‐TNF‐α and anti‐IgE monoclonal antibodies were used in 6 (15.4%) and 1 (2.6%) patients, respectively, with variable results. Surgery was the choice for 2 patients with good response.

Conclusions

OFG is a rare and neglected disease showing multiple clinical phenotypes. While early diagnosis is crucial, management is difficult and highly dependent on the expertise of clinicians due to the lack of international guidelines. There is a need to establish registry databases and address challenges of long‐term management.
Definitive pathognomonic signs and symptoms of paediatric neurological COVID‐19 are still emerging
Authors: Verrotti Alberto , Mazzocchetti Chiara , Iannetti Paola
Published: February 2021

Children with COVID‐19 tend to show milder symptoms than adults during the pandemic, but growing evidence of neurological involvement has emerged. Some studies have reported neurological symptoms in children with COVID‐19, which include multisystem inflammatory syndrome, a disease that shares some, but not all, of the characteristics of Kawasaki disease. This review presents, and discusses, the evidence to date. Our initial findings suggest that neurological manifestations can be considered to be the direct result of central nervous system viral invasion or post‐infection immuno‐mediated disease.
Trends in treatment episodes for methamphetamine smoking and injecting in Australia, 2003–2019
Authors: McKetin Rebecca , Chrzanowska Agata , Man Nicola , Peacock Amy , Sutherland Rachel , Degenhardt Louisa
Published: February 2021

Introduction

We examined trends in Australian treatment episodes for smoking and injecting methamphetamine from 2003 to 2019.

Methods

Data from the Alcohol and Other Drug Treatment National Minimum Data Set, where amphetamines were the principal drug of concern, were analysed from 2003 to 2019. Rates were calculated per 100 000 population aged 10–100 years. Joinpoint software was used to identify changepoints and estimate the annual percentage change (APC) in the rate of treatment episodes. Treatment episode characteristics were compared for smoking versus injecting in 2019.

Results

The rate of treatment episodes for methamphetamine increased from 77 to 262 per 100 000 population between 2003 and 2019 (average APC 8%, P < 0.001), this being due to treatment episodes for smoking methamphetamine (average APC 32%, P < 0.001) with no significant increase in treatment episodes for injecting methamphetamine (average APC 3%). Treatment episodes for smoking increased sharply from 2003 to 2008 (APC 72%, P < 0.001) and again from 2010 to 2016 (APC 46%, P < 0.001), this upward trend being attenuated between 2016 and 2019 (APC 7%, P = 0.012). Treatment episodes for methamphetamine smoking (cf. injecting) involved younger clients (median age 30 vs. 35 years, P < 0.001) who were more likely to receive assessment or case management only (37% vs. 29%, P < 0.001).

Discussion and Conclusions

Increased methamphetamine treatment episodes in Australia since 2003 are due mostly to smoking the drug, this occurring among younger cohort who receive less substantive treatment than clients who inject methamphetamine.
Combined endocytoscopy with pit pattern diagnosis in ulcerative colitis‐associated neoplasia: Pilot study
Authors: Kudo Shin‐ei , Maeda Yasuharu , Ogata Noriyuki , Misawa Masashi , Ogawa Yushi , Takishima Kazumi , Ishiyama Misaki , Mochizuki Kenichi , Minegishi Yosuke , Ogura Yohei , Abe Masahiro , Okumura Taishi , Matsudaira Shingo , Ishigaki Tomoyuki , Sasanuma Seiko , Mori Yuichi , Kudo Toyoki , Hayashi Takemasa , Wakamura Kunihiko , Miyachi Hideyuki , Baba Toshiyuki , Ishida Fumio , Nemoto Tetsuo , Hamatani Shigeharu , Ohtsuka Kazuo
Published: February 2021

Objectives

Ulcerative colitis‐associated neoplasias (UCAN) are often flat with an indistinct boundary from surrounding tissues, which makes differentiating UCAN from non‐neoplasias difficult. Pit pattern (PIT) has been reported as one of the most effective indicators to identify UCAN. However, regenerated mucosa is also often diagnosed as a neoplastic PIT. Endocytoscopy (EC) allows visualization of cell nuclei. The aim of this retrospective study was to demonstrate the diagnostic ability of combined EC irregularly‐formed nuclei with PIT (EC‐IN‐PIT) diagnosis to identify UCAN.

Methods

This study involved patients with ulcerative colitis whose lesions were observed by EC. Each lesion was diagnosed by two independent expert endoscopists, using two types of diagnostic strategies: PIT alone and EC‐IN‐PIT. We evaluated and compared the diagnostic abilities of PIT alone and EC‐IN‐PIT. We also examined the difference in the diagnostic abilities of an EC‐IN‐PIT diagnosis according to endoscopic inflammation severity.

Results

We analyzed 103 lesions from 62 patients; 23 lesions were UCAN and 80 were non‐neoplastic. EC‐IN‐PIT diagnosis had a significantly higher specificity and accuracy compared with PIT alone: 84% versus 58% (P < 0.001), and 88% versus 67% (P < 0.01), respectively. The specificity and accuracy were significantly higher for Mayo endoscopic score (MES) 0–1 than MES 2–3: 93% versus 68% (P < 0.001) and 95% versus 74% (P < 0.001), respectively.

Conclusions

Our novel EC‐IN‐PIT strategy had a better diagnostic ability than PIT alone to predict UCAN from suspected and initially detected lesions using conventional colonoscopy. UMIN clinical trial (UMIN000040698).
Hyriid mussels (Unionoida) enhance benthic organic matter and meiofauna densities in a temperate Australian river
Authors: McCasker Nicole , Humphries Paul
Published: February 2021

Studies in the Northern Hemisphere have shown that mussels play important roles as benthic‐pelagic couplers in freshwater systems, transferring filtered material, nutrients, and energy from the water column to sediments, through biodeposition and excretion. However, we know little of the functional roles of species of the Southern Hemisphere Hyriidae, the second most diverse family of the Unionoida.

The aims of this study were to determine the biodeposition and excretion rates of nutrients and organic matter of the hyriid Alathyria jacksoni in an unregulated Australian river and test experimentally if the physical structure and biodeposition of A. jacksoni influenced sediment nutrients, organic matter, periphyton concentrations and meiofauna densities.

In a lowland Australian river in late summer over 4 weeks, we measured biodeposition and excretion rates of A. jacksoni, and conducted a mesocosm experiment, during which we compared the effects of live mussels, dead mussel shells (shams), and controls without mussels on nutrients, organic matter, and meiofauna invertebrate densities in the sediment.

Mean (± SE) mass of biodeposition was 70.85 ± 3.20 mg mussel−1 hr−1 and the relative rates of inorganic and organic biodeposition were 60.9 ± 3.1 and 9.9 ± 0.8 mg mussel−1 hr−1, respectively. Organic matter was significantly greater in the sediment of the mesocosms with live mussels than in that of the control mesocosms. There was also a trend of greater mean sediment chlorophyll‐a and total nitrogen concentrations in mussel treatments than in the controls. No significant difference was detected in sediment total phosphorous between mussel and control enclosures.

The valves of live mussels had significantly higher amounts of organic material and chlorophyll‐a concentrations than the valves of sham mussels. There was a consistent trend of higher meiofauna densities collected in the benthos of the mussel enclosures than the control enclosures for total density and densities of Rotifera, Copepoda, Cladocera, Diptera, Oligocheata, Nematoda, and Ostracoda; this trend was near significant for total density; and significant for densities of Ostracoda, Rotifera, Cladocera, and Nematoda.

Using our biodeposition and excretion rate estimates, and estimates of population size of A. jacksoni in the Lower Ovens River, we estimated that in a typical 1‐km reach in a month over summer, A. jacksoni would be biodepositing approximately 4.8 kg/day of organic matter (dry mass), 137 g N/day and 19 g P/day, and excreting 21 g N/day and 3.7 g P/day.

Our findings are similar to those for Northern Hemisphere families of the Unionoida and serve to highlight the roles mussels play in processing of organic matter and cycling of nutrients in freshwater ecosystems.
Binge‐like ethanol drinking activates anaplastic lymphoma kinase signaling and increases the expression of STAT3 target genes in the mouse hippocampus and prefrontal cortex
Authors: Hamada Kana , Ferguson Laura B. , Mayfield R. Dayne , Krishnan Harish R. , Maienschein‐Cline Mark , Lasek Amy W.
Published: February 2021

Alcohol use disorder (AUD) has a complex pathogenesis, making it a difficult disorder to treat. Identifying relevant signaling pathways in the brain may be useful for finding new pharmacological targets to treat AUD. The receptor tyrosine kinase anaplastic lymphoma kinase (ALK) activates the transcription factor STAT3 in response to ethanol in cell lines. Here, we show ALK activation and upregulation of known STAT3 target genes (Socs3, Gfap and Tnfrsf1a) in the prefrontal cortex (PFC) and ventral hippocampus (HPC) of mice after 4 days of binge‐like ethanol drinking. Mice treated with the STAT3 inhibitor stattic drank less ethanol than vehicle‐treated mice, demonstrating the behavioral importance of STAT3. To identify novel ethanol‐induced target genes downstream of the ALK and STAT3 pathway, we analyzed the NIH LINCS L1000 database for gene signature overlap between ALK inhibitor (alectinib and NVP‐TAE684) and STAT3 inhibitor (niclosamide) treatments on cell lines. These genes were then compared with differentially expressed genes in the PFC of mice after binge‐like drinking. We found 95 unique gene candidates, out of which 57 had STAT3 binding motifs in their promoters. We further showed by qPCR that expression of the putative STAT3 genes Nr1h2, Smarcc1, Smarca4 and Gpnmb were increased in either the PFC or HPC after binge‐like drinking. Together, these results indicate activation of the ALK‐STAT3 signaling pathway in the brain after binge‐like ethanol consumption, identify putative novel ethanol‐responsive STAT3 target genes, and suggest that STAT3 inhibition may be a potential method to reduce binge drinking in humans.
In the human, true myocutaneous junctions of skeletal muscle fibers are limited to the face
Authors: May Christian Albrecht , Bramke Silvia
Published: February 2021

Within the panniculus carnosus‐associated skeletal muscles in the human, the palmaris brevis and the platysma showed myotendinous/myofascial junctions with clear distance to the corium and the specific connection collagen type XXII. The orbicularis oris muscle, in contrast, contained bundles of striated muscle fibers reaching the corium at two distinct levels: the predominant inner ending was connected to the elastic network of the inner corium and the outer ending was within the more superficial collagen network. At both locations, the striated muscle fibers showed brush‐like cytoplasmic protrusions connecting a network which was not oriented toward the muscle fibers. Collagen type XXII was not present.
Ultrasound patterns of different dermal filler materials used in aesthetics
Authors: Urdiales‐Gálvez Fernando , De cabo‐Francés Francisco M. , Bové Isabel
Published: February 2021

Background

Hyaluronic acid (HA) injection procedures has experienced an unprecedented increase.

Aims

To assess and determine, by using ultrasound examinations, the patterns corresponding to different dermal fillers.

Patients/Methods

Observational and retrospective bicenter study conducted on patients who underwent previous aesthetic treatments with dermal fillers. Ultrasound examinations were performed, at each study center, by one experienced observer.

Results

Sixty patients were included in the analysis. Among them, 48 patients showed a well‐defined ultrasound pattern, while 12 exhibited a mixed one. According to ultrasound images, 4 different patterns were identified: [1] Heterogeneous, characterized by alternating hyperechoic and anechoic areas, which are visualized in the tissue in a heterogeneous way. This pattern is associated with healthy skin/subcutaneous cellular tissue and with fully integrated HA fillers. [2] Fine grain snowfall, characterized by alternating hyperechoic imaging, with posterior echogenic shadows. It is typical of liquid injectable silicone. [3] Coarse grain snowfall, characterized by hyperechoic images distributed all over the tissue. This is typical of calcium hydroxyapatite and polymethyl methacrylate‐based fillers. [4] Globular, typical "cystic" imaging, with anechoic images indicative of liquid semi‐liquid content. This pattern is characteristic of polyalkylamides and polyacrylamides, and HA‐based fillers immediately after their injection. The presence of "mixed" patterns is mainly due to different aesthetic procedures performed at different times.

Conclusions

Ultrasound imaging may be a valuable tool for assessing the nature of former dermal filler procedures in daily practice. The identification of these patterns will allow specialists to choose the best therapeutic approach in patients who underwent previous aesthetictreatments.
Mid‐face reshaping using threads with bidirectional convergent barbs: A retrospective study
Authors: Santorelli Adriano , Cerullo Fabio , Cirillo Pierfrancesco , Cavallini Maurizio , Avvedimento Stefano
Published: February 2021

Background

Minimally invasive procedures, such as thread suspension techniques, are a growing trend for facial rejuvenation. However, not enough data are available on the efficacy, outcomes, and morbidity of suture suspension techniques in mid‐face reshaping.

Aims

Our goal was to assess treatment outcomes and patient satisfaction following mid‐face reshaping using threads with bidirectional convergent barbs (DefinisseTM free floating threads).

Patients/Methods

We performed a retrospective analysis of 60 patients who underwent treatment for mid‐face reshaping using DefinisseTM free floating threads. Response to treatment was assessed at 6 months using the mid‐face‐specific Mid‐Face Volume Deficit scale (Allergan®), Global Aesthetic Improvement and FACE‐QTM scales.

Results

Sixty patients underwent mid‐face treatment with the suspension thread technique (mean age 51.3, 90% female). No concomitant procedures were done. A reduction by one point or more in the Mid‐Face Volume Deficit Scale (MDFVS) score treatment was seen in all patients after 6 months. Mean overall MFVDS and FACE‐QTM scores were significantly improved. On the GAIS, most patients were rated as improved or better both by the evaluating investigators and during self‐assessment. No major complications were observed, and none of the patients requested the removal of the threads (mean follow‐up 9.8 months, range 6–14 months).

Conclusion

Our results suggest that mid‐face reshaping with DefinisseTM free floating threads is a safe and reliable procedure characterized by low complication rates and good esthetic results. This minimally invasive procedure is a good alternative for normal or combination skin patients who refuse or want to delay the need for traditional rhytidectomy.
Analysis of galectin‐3 levels as a source of coronary heart disease risk during periodontitis
Authors: Isola Gaetano , Polizzi Alessandro , Alibrandi Angela , Williams Ray C. , Lo Giudice Antonino
Published: February 2021

Background and Objective

Different evidence has shown that Galectins have a key role as modulators of cell surface functions and signaling in a wide range of inflammatory diseases during their preclinical stages. The aim of this study was to analyze the association and impact of periodontitis and coronary heart disease (CHD) on salivary and serum Galectin‐3 in patients with periodontitis and CHD.

Materials and Methods

For the present study, healthy controls (n = 38), periodontitis (n = 40), CHD (n = 39), and a combination of periodontitis +CHD (n = 38) patients were enrolled and analyzed. In each patient, demographic characteristics and a full‐mouth clinical periodontal examination were achieved. Moreover, serum and salivary samples were collected to assess Galectin‐3 and Endothelin‐1 (ET‐1) levels. The Jonckheere‐Terpstra p‐trend and Spearman's correlation tests as well as uni‐ and linear regression analyses were used to analyze the study data.

Results

Patients with periodontitis (serum, p = .003; saliva, p < .001) and periodontitis + CHD groups (serum p = .004; saliva, p < .001) had higher median serum and salivary concentrations of Galectin‐3 in comparison with CHD and healthy controls. Serum (p = .006) and salivary (p = .009) Galectin‐3 levels were significantly correlated with serum ET‐1. The multivariate regression analysis highlighted that periodontitis (p = .047) was the significant predictor of serum Galectin‐3 levels while ET‐1 (p = .028) was the significant predictor of salivary Galectin‐3 levels.

Conclusion

The results showed that patients with periodontitis and periodontitis + CHD presented significant higher serum and salivary Galectin‐3 levels in comparison with CHD patients and healthy subjects. Periodontitis and ET‐1 were the significant predictors of serum and salivary Galectin‐3 levels, respectively.
Association among periodontitis severity, anti‐agalactosyl immunoglobulin G titer, and the disease activity of rheumatoid arthritis
Authors: Kaneko Chihiro , Kobayashi Tetsuo , Ito Satoshi , Sugita Noriko , Murasawa Akira , Ishikawa Hajime , Tabeta Koichi
Published: February 2021

Objective

The aim of the present study was to evaluate the association between the periodontal and serological parameters and the disease activity of rheumatoid arthritis (RA) and between the anti‐agalactosyl immunoglobulin G (IgG) titer and periodontitis severity. The objective was also to assess the effect of supragingival scaling on the serological parameters in patients with RA.

Background

The periodontal and serological parameters in relation to the autoimmune inflammatory response have been linked to RA disease activity. However, the association of the anti‐agalactosyl IgG titer with RA disease activity and periodontitis severity has not been elucidated.

Methods

The periodontal, rheumatologic, and serological data were collected from 127 patients with RA in a retrospective cohort study. Of the 127 patients, 21 had been randomly assigned to receive oral hygiene instruction and supragingival scaling. The anti‐agalactosyl IgG titer was determined by an electrochemiluminescence immunoassay.

Results

The patients with a moderate to high RA disease activity showed significantly higher levels of probing depth (PD), clinical attachment level, anti‐cyclic citrullinated peptide IgG, and anti‐agalactosyl IgG titer and greater mean percentages of severe periodontitis than those with a low RA disease activity (p < .05 for all). Both univariate and multivariate analyses revealed a significantly positive correlation between the PD and RA disease activity (p = .009 and p = .001), between the anti‐agalactosyl IgG titer and RA disease activity (p = .002 and p < .001), and between the anti‐agalactosyl IgG titer and PD (p < .001 for both). Supragingival scaling significantly decreased the anti‐agalactosyl IgG titer (p = 0.03).

Conclusion

The PD and anti‐agalactosyl IgG titer are positively interrelated, both of which are correlated positively with RA disease activity and influenced by supragingival scaling in patients with RA.
Isolated bacterial infection without decompensation has no impact on survival of compensated patients with cirrhosis
Authors: Reichert Matthias C. , Schneider Christina , Greinert Robin , Casper Markus , Grünhage Frank , Wienke Andreas , Zipprich Alexander , Lammert Frank , Ripoll Cristina
Published: February 2021

Background & Aims

Bacterial infections (BI) affect the natural course of cirrhosis and were suggested to be a landmark event marking the transition to the decompensated stage. Our specific aim was to evaluate the impact of BI on the natural history of compensated cirrhosis.

Methods

We analyzed 858 patients with cirrhosis, evaluated for the INCA trial (EudraCT 2013‐001626‐26) in 2 academic medical centers between February 2014 and May 2019. Only patients with previously compensated disease were included. They were divided into 4 groups: compensated without BI, compensated with BI, 1st decompensation without BI, and 1st decompensation with BI.

Results

425 patients (median 61 [53‐69] years) were included in the final prospective analysis. At baseline, 257 patients were compensated (12 [4.7%] with BI), whereas 168 patients presented with their 1st decompensation (42 [25.0%] with BI). In patients who remained compensated MELD scores were similar in those with and without BI. Patients with their first decompensation and BI had higher MELD scores than those without BI. Amongst patients who remained compensated, BI had no influence on transplant‐free survival, whereas patients with their 1st decompensation and concurrent BI had significantly reduced transplant‐free survival as compared with those without BI. The development of BI or decompensation during follow‐up had a greater impact on survival than each of these complications at baseline.

Conclusions

In compensated patients with cirrhosis, the 1st decompensation associated to BI has worse survival than decompensation without BI. By contrast, BI without decompensation does not negatively impact survival of patients with compensated cirrhosis.
Epidemiological projections of viral‐induced hepatocellular carcinoma in the perspective of WHO global hepatitis elimination
Authors: Vo Quang Erwan , Shimakawa Yusuke , Nahon Pierre
Published: February 2021

Hepatitis B is an eminent risk factor for hepatocellular carcinoma (HCC) in Southeast Asia and sub‐Saharan Africa, whereas hepatitis C is a key risk factor for HCC in Western Europe and North America. Increased awareness of the global burden of viral hepatitis resulted, in May 2016, in the adoption of the first global health sector strategy on viral hepatitis by the World Health Assembly, which calls for the elimination of viral hepatitis as a public health threat by 2030. Although the incidence of liver cancer resulting from viral infections has increased since the 1990s, the implementation of public health interventions, such as hepatitis B vaccination and antiviral therapies might have reduced the global burdens of HCC. Hepatitis B immunization in infancy has been associated with a reduction in the risk of infant fulminant hepatitis, chronic liver disease, and HCC in Taiwan. Achieving viral hepatitis elimination by 2030 can be accelerated by improving the access to HCC screening programs. HCC surveillance programs in developed countries must be refined to increase an access to personalized surveillance program, whereas the limited access to surveillance and treatment of HCC in developing countries remains a significant public health issue.