bluuebunny/crossref_metadata_2025_split huggingface dataset:
IgG4‐positive plasma cells in Hashimoto thyroiditis: IgG4‐related disease or inflammation‐related IgG4‐positivity?
Authors: Lintusaari Jarkko , Vesaniemi Eini , Kalfert David , Ilvesaro Joanna , Ludvíková Marie , Kholová Ivana 
Published: June 2020

Despite the interest of researchers in IgG4‐related disease (IgG4‐RD), many questions still remain unanswered regarding the thyroid gland. We aimed to clarify the relationship between IgG4‐positive plasma cells and the histopathological pattern in the Hashimoto thyroiditis (HT) in a Finnish series. HT specimens (n = 280) were retrieved from the Department of Pathology, Fimlab Laboratories. After re‐evaluation, 82 (29%) cases (72 females and 10 males, 52 ± 17 years) with significant fibrosis were selected. CD38, IgG and IgG4 positivity in plasma cells was evaluated by immunohistochemistry. Adjusted IgG4‐positive plasma cells per HPF > 20 and IgG4‐ to IgG‐positive plasma cell ratio > 30% were adopted as threshold criteria and related to other morphological features. IgG4‐positive HT group included 13 cases (15% from fibrotic HT, 4.6% from all HT, 50 ± 15 years, 11 females) with adjusted HPF count 30 ± 5 (23–40) IgG4‐positive cells. IgG4‐positivity significantly correlated with the presence of lobulation, oncocytic metaplasia and certain type of fibrosis, fibrosis spread outside the gland, lymphocytes/plasma cells epithelial penetration, the predominance of microfollicles and follicular atrophy in the present study. Despite the persisting uncertainty whether HT is IgG4‐RD, HT with IgG4‐positive plasma cells is histopathologically distinct entity with some geographic variability.
Improving Access to Psychological Therapies (IAPT) in the United Kingdom: A systematic review and meta‐analysis of 10‐years of practice‐based evidence
Authors: Wakefield Sarah , Kellett Stephen , Simmonds‐Buckley Melanie , Stockton Daniel , Bradbury Abigail , Delgadillo Jaime 
Published: June 2020

ObjectivesImproving Access to Psychological Therapies (IAPT) is a national‐level dissemination programme for provision of evidence‐based psychological treatments for anxiety and depression in the United Kingdom. This paper sought to review and meta‐analyse practice‐based evidence arising from the programme.DesignA pre‐registered (CRD42018114796) systematic review and meta‐analysis.MethodsA random effects meta‐analysis was performed only on the practice‐based IAPT studies (i.e. excluding the clinical trials). Subgroup analyses examined the potential influence of particular methodologies, treatments, populations, and target conditions. Sensitivity analyses investigated potential sources of heterogeneity and bias.ResultsThe systematic review identified N = 60 studies, with N = 47 studies suitable for meta‐analysis. The primary meta‐analysis showed large pre‐post treatment effect sizes for depression (d = 0.87, 95% CI [0.78–0.96], p < .0001) and anxiety (d = 0.88, 95% CI [0.79–0.97], p < .0001), and a moderate effect on functional impairment (d = 0.55, 95% CI [0.48–0.61], p < .0001). The methodological features of studies influenced ESs (e.g., such as whether intention‐to‐treat or completer analyses were employed).ConclusionsCurrent evidence suggests that IAPT enables access to broadly effective evidence‐based psychological therapies for large numbers of patients. The limitations of the review and the clinical and methodological implications are discussed.Practitioner points

IAPT interventions are associated with large pre‐post treatment effect sizes in depression and anxiety measures.

IAPT interventions are associated with moderate treatment effect sizes with regards to work and social adjustment.

A reduction in dropout and also the prevention of post‐treatment relapse via the offer of follow‐up support are important areas for future development.
Crossroads of telomere biology and anticancer drug discovery
Authors: Seimiya Hiroyuki 
Published: June 2020

AbstractThe telomere is the specialized nucleoprotein complex at the end of the chromosome. Its highly conserved 5′‐TTAGGG‐3′ repeats and shelterin protein complexes form a protective loop structure to maintain the integrity and stability of linear chromosomes. Although human somatic cells gradually shorten telomeres to undergo senescence or crisis, cancer cells activate telomerase, or the recombination‐based mechanism to maintain telomeres and exhibit immortality. As the most frequent non‐coding mutations in cancer, gain‐of‐function mutations in the promoter region of the telomerase catalytic subunit, TERT, trigger telomerase activation. Promoter methylation and copy number gain are also associated with the enhanced TERT expression. Although telomerase inhibitors were pioneered from telomere‐directed therapeutics, their efficacies are limited to cancer with short telomeres and some hematological malignancies. Other therapeutic approaches include a nucleoside analog incorporated to telomeres and TERT promoter‐driven oncolytic adenoviruses. Tankyrase poly(ADP‐ribose) polymerase, a positive regulator of telomerase, has been rediscovered as a target for Wnt‐driven cancer. Meanwhile, telomeric nucleic acids form a higher‐order structure called a G‐quadruplex (G4). G4s are formed genome‐wide and their dynamics affect various events, including replication, transcription, and translation. G4‐stabilizing compounds (G4 ligands) exert anticancer effects and are in clinical investigations. Collectively, telomere biology has provided clues for deeper understanding of cancer, which expands opportunities to discover innovative anticancer drugs.
Phase II trial of pazopanib in patients with metastatic or unresectable chemoresistant sarcomas: A Japanese Musculoskeletal Oncology Group study
Authors: Urakawa Hiroshi , Kawai Akira , Goto Takahiro , Hiraga Hiroaki , Ozaki Toshifumi , Tsuchiya Hiroyuki , Nakayama Robert , Naka Norifumi , Matsumoto Yoshihiro , Kobayashi Eisuke , Okuma Tomotake , Kunisada Toshiyuki , Ando Masahiko , Ueda Takafumi , Nishida Yoshihiro 
Published: June 2020

AbstractAlveolar soft part sarcoma (ASPS), epithelioid sarcoma (ES), and clear cell sarcoma (CCS) are known to be chemoresistant tumors. The aim of this study was to investigate the effect of pazopanib on these chemoresistant tumors. This study is designed as a single‐arm, multicenter, investigator‐initiated phase II trial. Patient enrollment was undertaken between July 2016 and August 2018 at 10 hospitals participating in the Japanese Musculoskeletal Oncology Group. The primary end‐point is the CBR (CBR, including complete or partial response and stable disease) at 12 weeks after treatment with pazopanib according to RECIST. Eight patients were enrolled within the period. The histological subtypes were 5 ASPS, 2 ES, and 1 CCS. The median follow‐up period was 22.2 (range, 4.9‐24.9) months. All patients initially received pazopanib 800 mg once daily. The CBRs were 87.5% (7 of 8) and 75.0% (6 of 8) according to RECIST and Choi criteria at 12 weeks after pazopanib treatment, respectively. The CBRs at 12 weeks according to RECIST were 80.0%, 100.0%, and 100.0% in ASPS, ES, and CCS, respectively. Partial response was observed in 1 ASPS according to RECIST and 3 ASPS and 1 ES according to Choi criteria at 12 weeks after pazopanib treatment. This study documented antitumor activity of pazopanib, especially in ASPS. These results support the frontline use of pazopanib for ASPS. Prospective data collection is desired using both RECIST and Choi criteria for these rare chemoresistant tumors.
Social story‐based oral health promotion for preschool children with special healthcare needs: A 24‐month randomized controlled trial
Authors: Zhou Ni , Wong Hai Ming , McGrath Colman 
Published: June 2020

AbstractObjectivesThis study aimed to investigate the efficacy of the social story‐based intervention in promoting the oral health status among preschool children with special healthcare needs.MethodsThe 24‐month randomized controlled trial recruited 306 children from centres that provided educational training for 2‐ to 6‐year‐old children who had special healthcare needs. The participants received standardized toothbrushing training and oral health education materials. The education materials for children in the test group were validated social stories, while materials for children in the control group were standard leaflets. Those materials were introduced in each training session and used at home by parents. Children's oral health status and oral health‐related behaviours were assessed before and after interventions. Data were analysed via generalized estimating equations, negative binomial regression and binary logistic regression.ResultsThere was no significant difference in caries experience among children in both groups after 24 months. However, children in the test group showed better oral hygiene status and better toothbrushing performance, and they were more likely to visit a dentist (OR = 2.00, 95% CI:1.15,3.49) than their peers in the control group. Caries progression was more likely to be observed among children who had low social skills or whose parents were not working full‐time. Children from high‐income families showed better oral hygiene status than their peers (Estimate = −0.11, 95%CI: −0.20,−0.01).ConclusionSocial stories could be used to improve oral health‐related behaviours among young children with SHCN. The efficacy of the intervention might be associated with children's adaptive skills and family socio‐demographic status.
Neutrophil elastase and endogenous inhibitors in Behçet's disease saliva
Authors: Novak T , Fortune F , Bergmeier L , Khan I , Hagi-Pavli E 
Published: June 2020

Summary
Behçet's disease (BD) is a vasculitis of unknown aetiology typified by chronic recurrent oral ulcers and systemic inflammatory manifestations. Neutrophils, and specifically their protease neutrophil elastase (NE), have been implicated in its pathology. Although NE is an effective anti-microbial, excessive NE can damage host tissue. Recurrent oral ulceration is a primary BD symptom, therefore we hypothesized that excessive neutrophil infiltration evidenced by increased NE and a reduction in specific endogenous inhibitors, secretory leucocyte protease inhibitor (SLPI) and alpha1-anti-trypsin (α1AT) contributes to BD mucosal instability. NE, SLPI and α1AT were quantified in saliva from BD patients with active oral ulcers (BDa) and quiet without ulcers (BDq), recurrent aphthous stomatitis (RASa; RASq) and healthy controls (HC). Although BDq saliva had marginally higher median NE levels (1112 ng/ml) compared to both RASq (1043 ng/ml) and HC (999 ng/ml), SLPI was significantly reduced in BDq (P &lt; 0·01). Despite decreased SLPI protein, mRNA expression was significantly increased in BDq buccal epithelial swabs compared to RASq and HC (P &lt; 0·05, P &lt; 0·001). NE remained enzymatically active, although α1AT levels were at least eight times higher than SLPI in all groups, suggesting that α1AT does not have a primary role in counteracting NE in saliva. Furthermore, NE levels in BDa patients medicated with both azathioprine (AZA) and colchicine (COLC) were significantly lower than those on COLC (P = 0·0008) or neither (P = 0·02), indicating that combining AZA + COLC may help to regulate excessive NE during ulceration. This study showed that enzymatically active NE coupled with reduced SLPI in BD saliva may contribute to recurrent oral ulcerations.
A homozygous stop gain mutation in BOD1 gene in a Lebanese patient with syndromic intellectual disability
Authors: Hamdan Nadine , Mehawej Cybel , Sebaaly Ghada , Jalkh Nadine , Corbani Sandra , Abou‐Ghoch Joelle , De Backer O. , Chouery Eliane 
Published: June 2020

AbstractIntellectual disability (ID) is a neurodevelopmental disorder characterized by limitations in both intellectual and behavioral functioning. It can occur in non‐syndromic and syndromic forms involving multiple organs. While the majority of genetic variants linked to ID are de novo, inherited variants are also detected in some forms. Here, we report a consanguineous Lebanese family presenting with an autosomal recessive syndromic ID characterized by neurodevelopmental delay, mild dysmorphic features, hearing impairment and endocrine dysfunction. Whole exome sequencing enabled the detection of the homozygous nonsense mutation in BOD1, p.R151X, in the proband. BOD1 is required for chromosomes biorientation during cell division. It also contributes to the regulation of cell survival and to the modulation of fatty acid metabolism. Another nonsense mutation in BOD1 was linked to ID in a consanguineous Iranian family. This is the second report of BOD1 mutations in humans and the first in a syndromic ID including gonadal dysfunction and high‐frequency hearing impairment. Our findings confirm the involvement of BOD1 in cognitive functioning and expand the clinical spectrum of BOD1 deficiency.
Prospective anatomical study to determine the site of insertion of recurrent laryngeal nerve into the larynx
Authors: Wu James X. , Hanson Martin , Lohia Shivangi , Li Hao , Wang Laura , Shaha Ashok R. , Ganly Ian 
Published: June 2020

AbstractObjectivesDetermine whether the insertion site of the recurrent laryngeal nerve (RLN) occurs at a predictable distance from the midline trachea, to help guide safe dissection during thyroid surgery.DesignProspective clinical trial. At the inferior edge of the cricoid cartilage, we measured the distance from mildline trachea to the RLN insertion site.SettingSingle institution.Participants50 consecutive patients undergoing thyroid surgery.Main outcome measuresDistance from midline trachea to laryngeal insertion of RLN.ResultsThe study population included 36 women and 14 men, with 72 total nerves measured. The average distance‐to‐midline + standard deviation (range) of the RLN was 20.7 + 2.3 (17‐26) mm in women compared to 26.3 + 2.1 (22‐32) mm in men.ConclusionThe insertion point of the RLN into the larynx at the level of inferior border of the cricoid cartilage can be reliably predicted, to facilitate early identification of the RLN during thyroid surgery.
The histopathological spectrum of Melkersson‐Rosenthal syndrome: Analysis of 47 cases
Authors: Gavioli Camila Fátima Biancardi , Nico Marcello Menta Simonsen , Florezi Giovanna Piacenza , Lourenço Silvia Vanessa 
Published: June 2020

AbstractBackgroundMelkersson‐Rosenthal syndrome (MRS) is a rare disease characterized by the triad of recurrent orofacial edema, relapsing facial paralysis and plicated tongue. Histopathological features of MRS have not been extensively analyzed.MethodsThis study investigated the histopathological aspects of oral lesions from 47 MRS patients.ResultsThe most common biopsy site was the upper lip, followed by the lower lip, gingiva and palate. The most important findings were ill‐defined and well‐formed granulomas. Lymphoplasmacytic inflammatory infiltrate was seen in early and late stages of MRS. Edema, fibrosis, vasodilatation and congestion were the most common finding in the lamina propria. Gingival and palate exams also demonstrated granulomatous infiltrates. Regarding the evolution time of the disease, we demonstrated that, in initial phases, there is a lymphoplasmacytic inflammatory infiltrates, followed by a granulomatous infiltrate and, subsequently, fibrosis.ConclusionHistopathological examination of oral lesions is helpful for the diagnosis of MRS; the absence of granulomatous inflammation does not exclude the diagnosis of syndrome. Clinical and histopathological analysis of the rare gingival and palate lesions is important, since all histopathological findings of the disease were detected in these sites.
Cutaneous leishmaniasis: A pathological study of 360 cases with special emphasis on the contribution of immunohistochemistry and polymerase chain reaction to diagnosis
Authors: Cardozo Rocío S. , García‐Montero Pedro P. , Chicharro Carmen , Tardío Juan C. 
Published: June 2020

AbstractBackgroundTraditional methods for the diagnosis of leishmaniasis yield poor sensitivity, which limits its effectiveness in lesions with a low parasite burden.MethodsRetrospective pathologic study of 360 cases of cutaneous leishmaniasis and analysis of the different diagnostic methods used.ResultsIn 93% of the lesions, histopathology showed a dense and diffuse inflammatory infiltrate, consisting of lymphocytes, histiocytes and plasma cells, which occupied the superficial and mid dermis and variably extended to deep dermis and superficial subcutis (standard pattern). The remaining cases exhibited atypical features, such as perivascular, interstitial or perifollicular inflammatory patterns, folliculitis or panniculitis. Granulomas were identified in 84% of biopsies, most of them as small, poorly formed, non‐necrotizing histiocytic aggregates. Amastigotes were visualized by routine histopathologic exam in 36% of biopsies. Immunohistochemistry stained 17 of 26 lesions (65%) negative by conventional stains. PCR provided the correct diagnosis in 218 cases (58% of the series) negative for Leishmania by other techniques.ConclusionsBiopsies negative for Leishmania by traditional diagnostic methods that show the histopathologic standard pattern, those with atypical features from patients with clinical suspicion of cutaneous leishmaniasis in endemic areas, should be studied by immunohistochemistry and/or PCR for Leishmania in order to reach the definitive diagnosis.
Chondrodermatitis nodularis nasi
Authors: Kasitinon Stacy Yuan , Vandergriff Travis 
Published: June 2020

AbstractChondrodermatitis nodularis helicis is a relatively common ulcerative, inflammatory condition affecting the skin, and cartilage of the ear. We present a case of chondrodermatitis affecting the skin and cartilage of the nose, designated chondrodermatitis nodularis nasi. Clinically, chondrodermatitis presents as a singular, painful, ulcerated papule or nodule that results from prolonged pressure, trauma, sun exposure, or vascular compromise. The clinical features resemble those seen in skin cancer, and a biopsy is often required to secure the diagnosis. Histopathologic analysis of chondrodermatitis demonstrates a central ulcer, beneath which there is fibrinoid necrosis of the dermis and inflammatory infiltrates. The ulcer is bordered by pseudoepitheliomatous hyperplasia with underlying granulation tissue. In addition to a clinical and morphologic description of chondrodermatitis nodularis nasi, a discussion of etiological factors and differential diagnoses is included. Increased recognition and reporting of the condition will allow for the exploration of optimal treatment strategies.
Psychosocial factors associated with HbA1c in adults with insulin pump‐treated type 1 diabetes: a systematic review
Authors: Schmidt S. , Andersen Nexø M. , Norgaard O. , Willaing I. , Pedersen‐Bjergaard U. , Skinner T. C. , Nørgaard K. 
Published: June 2020

AbstractAimsTo identify currently available studies on the association between psychosocial factors and HbA1c in adults with insulin pump‐treated type 1 diabetes, by performing a systematic review of the literature.MethodsMEDLINE, Embase, CINAHL and PsycINFO were searched for original studies on the association between psychosocial factors and HbA1c in ≥ 50 adult, non‐pregnant, insulin pump users with type 1 diabetes.ResultsThe search resulted in 1777 unique records, of which eight were eligible for inclusion. All identified studies were observational, with sample sizes ranging from 51 to 214. Seven different psychosocial factors were investigated in the eight studies. Study analysis suggested that HbA1c may be associated with diabetes numeracy and quality of life. There were no indications of associations between HbA1c and fear of hypoglycaemia or self‐efficacy. Results regarding associations between HbA1c and coping style, diabetes distress and locus of control were inconsistent.ConclusionsThis systematic review summarizes the currently limited information on the association between psychosocial factors and HbA1c during insulin pump therapy. The evidence base of the included studies was weak, and this review highlights the need for more research in these areas, with improved methodological and theoretical frameworks, including exploration of a broader spectrum of psychosocial variables and their potential association with HbA1c and other metabolic outcomes.(PROSPERO International prospective register of systematic reviews registration no: CRD42020145705).
“Individual Placement and Support” boosts employment for early psychosis clients, even when baseline rates are high
Authors: Erickson David H. , Roes Meighen M. , DiGiacomo Alessandra , Burns Amy 
Published: June 2020

AbstractAimIndividual Placement and Support is an effective vocational intervention for increasing competitive employment for people with severe mental illness. Little is known, however, about its effectiveness in the context of early psychosis. This study assesses improvements in clients' employment in a phase of illness during which functional abilities often decline.MethodsThe trial design is an assessor‐blinded randomized clinical trial, set in the context of a population‐based Early Psychosis Intervention program in British Columbia, Canada. Participants were randomized either to 1 year of employment support added to treatment‐as‐usual, or the latter alone. Interviews at intake captured data regarding demographics, symptom severity, and employment; assessments at 6 and 12 months repeated queries about employment activities.ResultsA total of 109 clients were recruited. Employment rates in the Individual Placement and Support group increased over time, unlike the control group. Further, the number of days worked over the 12‐month intervention period, compared to the 6 months prior to the study, improved for both groups, but the increase was greater among clients receiving IPS. Sensitivity analysis indicated the advantage in days worked was evident in the second half of the intervention period (6‐12 months), but not the first half.ConclusionsEmployment rates, for younger clients in both early‐psychosis groups, were high compared to older clients in later stages of illness. In this study, use of the Individual Placement and Support strategy further increased employment, despite the high baseline rates. Further research is needed to identify the optimal timing of employment support for these clients.
Sex matters in neuroscience and neuropsychopharmacology
Authors: Pawluski Jodi L. , Kokras Nikolaos , Charlier Thierry D. , Dalla Christina 
Published: June 2020

AbstractPrevalence and symptoms of most psychiatric and neurological disorders differ in men and women and there is substantial evidence that their neurobiological basis and treatment also differ by sex. This special issue sought to bring together a series of empirical papers and targeted reviews to highlight the diverse impact of sex in neuroscience and neuropsychopharmacology. This special issue emphasizes the diverse impact of sex in neuroscience and neuropsychopharmacology, including 9 review papers and 17 research articles highlighting investigation in different species (zebrafish, mice, rats, and humans). Each contribution covers scientific topics that overlap with genetics, endocrinology, cognition, behavioral neuroscience, neurology, and pharmacology. Investigating the extent to which sex differences can impact the brain and behavior is key to moving forward in neuroscience research.