bluuebunny/crossref_metadata_2025_split huggingface dataset:
Downregulation of miR‐26 promotes invasion and metastasis via targeting interleukin‐22 in cutaneous T‐cell lymphoma
Authors: Matsuda Yuka , Ikeda Sho , Abe Fumito , Takahashi Yuto , Kitadate Akihiro , Takahashi Naoto , Wakui Hideki , Tagawa Hiroyuki 
Published: February 2022

AbstractIt has been reported that certain microRNAs (miRNA) are associated with the pathogenesis of lymphoma. We have previously demonstrated that histone deacetylase inhibitors restore tumor‐suppressive miRNAs, such as miR‐16, miR‐29, miR‐150, and miR‐26, in advanced cutaneous T‐cell lymphoma (CTCL). Among these, the function of miR‐26 remains unclear. In this study, we aimed to reveal the function of miR‐26 in CTCL oncogenesis. First, we confirmed that the miR‐26 family was markedly dysregulated in CTCL cell lines and primary samples. In vivo analysis using miR‐26a‐transduced CTCL cells injected into immunodeficient NOG mice demonstrated the significant prolonged survival of the mice, suggesting that the miRNA had a tumor‐suppressive function. We performed gene expression assays and identified 12 candidate miR‐26 targets, namely RGS13, FAM71F1, OAF, SNX21, CDH2, PTPLB, IL22, DNAJB5, CASZ1, CACNA1C, MYH10, and CNR1. Among these, IL22 was the most likely candidate target because the IL‐22–STAT3–CCL20–CCR6 cascade is associated with tumor invasion and metastasis of advanced CTCL. In vitro analysis of IL22 and IL22RA knockdown and miR‐26 transduction demonstrated inhibited CTCL cell migration. In particular, IL22 knockdown induced cell apoptosis. Finally, we conducted in vivo inoculation analysis of mice injected with shIL22‐transfected CTCL cells, and found no tumor invasion or metastasis in the inoculated mice, although the control mice showed multiple tumor invasions and metastases. These results, along with our previous data, demonstrated that miR‐26 is a tumor suppressor that is associated with tumor invasion and the metastasis of advanced CTCL by regulating the IL‐22–STAT3–CCL20 cascade. Therefore, a IL‐22‐targeting therapy could be a novel therapeutic strategy for advanced CTCL.
Comorbidity of atopic diseases and gastro‐oesophageal reflux: evidence of a shared cause
Authors: Brew Bronwyn K. , Almqvist Catarina , Lundholm Cecilia , Andreasson Anna , Lehto Kelli , Talley Nicholas J. , Gong Tong 
Published: February 2022

AbstractIntroductionGastro‐oesophageal reflux disease (GERD) is the most common non‐allergic comorbidity in adults with asthma; however, comorbidity with other atopic diseases such as eczema and hay fever is unclear. The objective was to assess the comorbidity of GERD with asthma and atopic diseases and to investigate possible mechanisms, including genetic and/or affective factors.MethodsA co‐twin control study harnessing 46 583 adult twins. Questionnaires on health status were linked to national patient and prescribed drug register data. Analyses tested associations of comorbidity between multiple definitions of atopic diseases (self‐report and register‐based) with GERD. Comparisons were made between unpaired, monozygotic (MZ) and dizygotic (DZ) twins to assess genetic liability. Affective traits (depression, anxiety and neuroticism) were added to models as possible explanatory factors.ResultsThe risk of GERD in those with asthma was OR (odds ratio) 1.52 (95% CI 1.38, 1.68), hay fever OR 1.22 (95%CI 1.12, 1.34) and eczema OR 1.23 (95%CI 1.10, 1.38). Adjusting for affective traits completely attenuated the comorbidity associations for hay fever and eczema with GERD, and partly for asthma with GERD. Co‐twin control associations attenuated suggesting a shared cause for both GERD and atopic diseases. For example, all twins adjOR 1.32 (95%CI 1.00, 1.74), 0.97 (95% CI 0.76–1.23) and 1.11 (95%CI 0.85–1.45) for self‐report asthma, hay fever and eczema with GERD respectively.ConclusionsGERD is a common comorbidity in adults with asthma, hay fever and/or eczema. We found evidence for shared mechanisms suggesting common underlying causes that may involve affective traits requiring further investigation.
Systemic inflammatory syndrome in children with FARSA deficiency
Authors: Charbit‐Henrion Fabienne , Goguyer‐Deschaumes Roman , Borensztajn Keren , Mirande Marc , Berthelet Jérémy , Rodrigues‐Lima Fernando , Khiat Anis , Frémond Marie‐Louise , Bader‐Meunier Brigitte , Rodari Marco M. , Seabra Luis , Rice Gillian I. , Legendre Marie , Drummond David , Berteloot Laureline , Roux Charles‐Joris , Boddaert Nathalie , Drabent Philippe , Molina Thierry Jo , Lacaille Florence , Kossorotoff Manoelle , Cerf‐Bensussan Nadine , Parlato Marianna , Hadchouel Alice 
Published: February 2022

AbstractVariants in aminoacyl‐tRNA synthetases (ARSs) genes are associated to a broad spectrum of human inherited diseases. Patients with defective PheRS, encoded by FARSA and FARSB, display brain abnormalities, interstitial lung disease and facial dysmorphism. We investigated four children from two unrelated consanguineous families carrying two missense homozygous variants in FARSA with significantly reduced PheRS‐mediated aminoacylation activity. In addition to the core ARS‐phenotype, all patients showed an inflammatory profile associated with autoimmunity and interferon score, a clinical feature not ascribed to PheRS‐deficient patients to date. JAK inhibition improved lung disease in one patient. Our findings expand the genetic and clinical spectrum of FARSA‐related disease.
The impact of transportation development on land price differences between cities: Widening or narrowing?—A case study based on the provincial level of Mainland China
Authors: Li Tianshu , Chen Zhigang 
Published: February 2022

AbstractExploring the impact of transportation development on land price differences between cities is of great significance to help guide the optimal allocation of land resources and promote the coordinated and balanced development of regions. This paper first discusses how regional transportation development influences land price differences between cities at a theoretical level. Then, by taking 26 provincial regions in the Chinese Mainland as research units, the specific effects of provincial transportation development on land price differences between cities are examined empirically by constructing econometric models. The results show that: (a) in recent years, the price of urban land in China has increased significantly, and the land price differences between cities are increasing in most provinces; and (b) provincial transportation development has a narrowing effect on land price differences between cities, and the spatial spillover effect brought by transportation development deserves attention. In the future, the role of transportation development in narrowing regional land price differences should be taken into consideration to promote the balanced development of the land market and the coordinated development of regions.
Phase 2 study of avatrombopag in Japanese patients with chronic liver disease and thrombocytopenia
Authors: Eguchi Yuichiro , Takahashi Hirokazu , Mappa Silvia , Santagostino Elena 
Published: February 2022

AbstractAimAvatrombopag, a thrombopoietin receptor agonist, can reduce the need for platelet transfusions or rescue interventions for bleeding in patients with chronic liver disease (CLD) and thrombocytopenia undergoing scheduled procedures. A model analysis indicated that the effect of avatrombopag on platelet production was reduced in East Asian versus non‐East Asian patients; however, the difference was deemed not clinically significant. Furthermore, a subgroup analysis of pooled Phase 3 trials showed similar avatrombopag efficacy across racial subgroups. The aim of this Phase 2 study was to corroborate the efficacy and safety of avatrombopag in Japanese patients with thrombocytopenia due to CLD.MethodsJapanese patients with CLD and thrombocytopenia were randomized to receive placebo or avatrombopag 20, 40, or 60 mg daily for 5 days. The primary endpoint was responder rate in platelet counts at Visit 4 (10–13 days after treatment initiation), defined as the proportion of patients with platelet count ≥50 × 109/L and ≥20 × 109/L increase from baseline.ResultsThirty‐nine patients were randomized and completed the study (placebo, n = 11; avatrombopag 20 mg, n = 7; 40 mg, n = 11; 60 mg, n = 10). Avatrombopag treatment was associated with significant increases in responder rate at Visit 4 in the 40 mg (63.6%; p = 0.004) and 60 mg (40%; p = 0.024) groups versus placebo (9.1%). Avatrombopag was well tolerated and no new safety signals were detected.ConclusionsEfficacy and safety results from this study were consistent with previous studies in patients with CLD and thrombocytopenia undergoing elective procedures, supporting treatment with avatrombopag in the Japanese population. ClinicalTrials.gov identifier: NCT02227693.
Effects of watercress extract fraction on R‐spondin 1‐mediated growth of human hair
Authors: Hashimoto Masakazu , Kawai Yuka , Masutani Teruaki , Tanaka Kiyotaka , Ito Kenichi , Iddamalgoda Arunasiri 
Published: February 2022

AbstractObjectiveHair loss and greying affect men and women of all ages, often causing psychosocial difficulties. Dickkopf‐1 (DKK1), a major hair loss factor secreted from dermal papilla (DP) cells in response to the secretion of dihydrotestosterone (DHT), has been reported to induce and accelerate androgenetic alopecia (AGA). In addition, DKK1 acts as a potent suppressor of melanogenesis and is closely related to hair colour. R‐spondin 1 (RSPO1) is a secretory agonist of Wnt signalling known to antagonize the effects of DKK1, including DKK1‐mediated hair follicle suppression. In this study, we investigated the effect of watercress extract (WCE) on the secretion of RSPO1 and DKK1 from DP cells as well as its anti‐hair loss effect in human hair follicles and patients.MethodsThe in vitro secretion of RSPO1 and DKK1 was measured by ELISA. Human hair follicles were collected from the scalp of a female donor and used for ex vivo organ culture to investigate the effects of WCE on human hair loss. Finally, a 6‐month human clinical trial was conducted to examine the effect of WCE‐containing lotion on hair growth in a male panel.ResultsWCE significantly upregulated RSPO1 secretion and suppressed DKK1 secretion in a dose‐dependent manner, even in the presence of DHT. WCE‐treated hair follicles elongated 1.6‐fold compared with the control, and the level of RSPO1 production in DP as well as RSPO1 bound to the outer root sheath (ORS) increased. In the clinical trial, the hair lotion containing 2% WCE increased hair thickness and density to improve against hair loss symptoms.ConclusionWCE exhibited a strong anti‐androgenic effect through its ability to suppress DKK1 secretion and antagonize DKK1 via RSPO1. These findings highlighted the potential use of WCE for the treatment of hair loss.
Probiotic mouthwash as an adjunct to mechanical therapy in the treatment of stage II periodontitis: A randomized controlled clinical trial
Authors: Ranjith Ambili , Nazimudeen Niyas Bin , Baiju Kamalasanan Vijayakumary 
Published: February 2022

AbstractObjectivesDysbiosis of oral microbiome play an integral role in periodontitis. Bacterial balance is an important aspect of host defence. Mechanical debridement alone is insufficient to manage many cases. Probiotics are a novel adjunctive strategy, but the beneficial effects of probiotics in the management of moderate periodontitis have not been evaluated before. The objective of the present study was to assess the efficacy of probiotic mouth rinse of Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium longum and Saccharomyces boulardii as an adjunct to mechanical debridement in grade II periodontitis. The study also evaluated change in salivary pH and IgA in both groups.MethodsThe study was registered under Clinical Trial Registry of India (CTRI NO: CTRI/2019/10/021630). 60 patients with stage II periodontitis were randomized into probiotic and placebo group (n = 30 in each group) after mechanical debridement. Patients were instructed to use mouth rinse twice a day for 30 days. Periodontal parameters (Plaque index, Gingival index, Pocket depth and clinical attachment level) were recorded at baseline, after 1 and 3 months. Salivary pH was tested using a pH metre and IgA using enzyme linked immunosorbent assay.ResultsSignificant improvement in all clinical parameters were noted in both the groups after 1 and 3 months. Intergroup comparison revealed significant difference in gingival index, probing depth and clinical attachment gain. Significant elevation of salivary IgA and pH was noticed in probiotic group in contrast to placebo group.ConclusionThe present study supports the use of probiotic mouthwash as an adjunct to mechanical therapy for the management of stage II periodontitis.
Smartphone de‐addiction among children and adolescents: An hour of need
Authors: Nayak Shalini G. , Pai Mamatha Shivananda 
Published: February 2022

AbstractSudden closure of schools due to coronavirus disease 2019 (COVID‐19) pandemic introduced extensive use of digital technology in education across the globe. The gadgets connected to the internet have become an essential part of the lives of children in the contemporary world. Children and adolescents are more exposed to smart devices for academic learning and entertainment. The concern of smartphone addiction among children and adolescents in recent decades has been heightened by the spread of COVID‐19. Excessive use of smartphones has physical, psychological, and social unfavorable outcomes signifying the need for developing strategies to reduce the usage.
Women's experiences and perceptions of women‐centered care and respectful care during facility‐based childbirth: A meta‐synthesis
Authors: Miyauchi Ai , Shishido Eri , Horiuchi Shigeko 
Published: February 2022

AbstractAimThe World Health Organization has recommended intrapartum care for a positive childbirth experience through respectful care based on women‐centered care. This study aimed to explore women's experiences of facility‐based childbirth to gain insights into their perceptions of women‐centered care, including humanized childbirth and respectful maternity care during intrapartum care.MethodsUsed the Joanna Briggs Institute method as the framework for this meta‐synthesis, we searched the PubMed, EMBASE, CINAHL, PsycINFO, and LILCAS databases, and included qualitative studies and interviews of women's experiences and perceptions of women‐centered care during facility‐based childbirth published from 1990 to 2020 in English. Study quality was assessed using the Critical Appraisal Skills Programme checklist. NVivo software was used for data extraction and synthesis.ResultsThere were 22 studies from 19 countries that met the established inclusion criteria. Five categories of experiences of facility‐based childbirth and perceptions of women‐centered care from the synthesized voices of women were generated: (i) value of women through childbirth; (ii) overwhelmed by unpleasant childbearing experiences; (iii) a sense of being respected and valued; (iv) a sense of being disrespected and abused; and (v) inadequate systems and resources. Our meta‐synthesis indicated that respectful and helpful interaction between women and healthcare providers produced positive perceptions among women.ConclusionsThis study emphasizes the importance of respectful interactions and intrapersonal experiences. Strong systems and positive environments lead to positive interactions between women and healthcare providers. Future studies need to consider cultural and economic differences in women‐centered care and respectful care for childbirth in different contexts.
Clinical exome sequencing for diagnosing severe cryptogenic liver disease in adults: A case series
Authors: Pelusi Serena , Ronzoni Luisa , Malvestiti Francesco , Bianco Cristiana , Marini Ilaria , D'Ambrosio Roberta , Giannotta Juri Alessandro , Soardo Giorgio , Maggioni Marco , Prati Daniele , Valenti Luca 
Published: February 2022

AbstractLiver diseases remain unexplained in up to 30% of adult patients; genetic analysis could help establish the correct diagnosis. In six adult patients with cryptogenic liver disease, we performed whole‐exome sequencing (WES) and evaluated the individual predisposition to progressive fatty liver disease by polygenic risk scores (PRS). In one patient, WES was allowed to diagnose the Hermansky–Pudlak syndrome. In the other two patients, genetic variants in LDLRAP1/MSH6 and ALDOB genes were identified, contributing to explaining the clinical presentation and disease pathogenesis (50% diagnostic uptake). In the other three patients, rare variants with a high likelihood of disrupting protein function in APOB, ATP7B, ABCB4 and ATP8B1 were identified. One patient who developed hepatocellular carcinoma during the follow‐up had a high PRS value. The study supports the role of WES, combined with risk stratification by PRS and accurate clinical assessment in improving the diagnosis and informed management in patients with cryptogenic liver disease, a positive family history or severe fatty liver not fully accounted for by environmental triggers.
Rapid increase in Omicron infections in England during December 2021: REACT-1 study
Authors: Elliott Paul , Bodinier Barbara , Eales Oliver , Wang Haowei , Haw David , Elliott Joshua , Whitaker Matthew , Jonnerby Jakob , Tang David , Walters Caroline E. , Atchison Christina , Diggle Peter J. , Page Andrew J. , Trotter Alexander J. , Ashby Deborah , Barclay Wendy , Taylor Graham , Ward Helen , Darzi Ara , Cooke Graham S. , Chadeau-Hyam Marc , Donnelly Christl A. 
Published: February 2022

The unprecedented rise in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during December 2021 was concurrent with rapid spread of the Omicron variant in England and globally. We analyzed the prevalence of SARS-CoV-2 and its dynamics in England from the end of November to mid-December 2021 among almost 100,000 participants in the REACT-1 study. Prevalence was high with rapid growth nationally and particularly in London during December 2021, with an increasing proportion of infections due to Omicron. We observed large decreases in swab positivity among mostly vaccinated older children (12 to 17 years) relative to unvaccinated younger children (5 to 11 years), and in adults who received a third (booster) vaccine dose versus two doses. Our results reinforce the importance of vaccination and booster campaigns, although additional measures have been needed to control the rapid growth of the Omicron variant.
Impact of cascade screening for catecholaminergic polymorphic ventricular tachycardia type 1
Authors: Shimamoto Keiko , Ohno Seiko , Kato Koichi , Takayama Koichiro , Sonoda Keiko , Fukuyama Megumi , Makiyama Takeru , Okamura Satomi , Asakura Koko , Imanishi Noriaki , Kato Yoshiaki , Sakaguchi Heima , Kamakura Tsukasa , Wada Mitsuru , Yamagata Kenichiro , Ishibashi Kohei , Inoue Yuko , Miyamoto Koji , Nagase Satoshi , Kusano Kengo , Horie Minoru , Aiba Takeshi 
Published: February 2022

ObjectiveHuman cardiacryanodine receptor 2(RYR2) shows autosomal-dominant inheritance in catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1); however,de novovariants have been observed in sporadic cases. Here, we investigated CPVT1-relatedRYR2variant inheritance and its clinical significance between familial andde novocases.MethodsWe enrolled 82 independent CPVT1 probands (median age: 10.0 (7.0–13.0) years; 45 male) carrying theRYR2variants and whose biological origin could be confirmed by parental genetic analysis: assured familial inheritance (familial group: n=24) andde novovariants (de novogroup: n=58). We examined the clinical characteristics of the probands and their family members carrying theRYR2variants.ResultsIn thede novogroup, theRYR2variants were more likely located in the C-terminus domain and less likely in the N-terminus domain than those in the familial group. The cumulative incidence of the first cardiac events (syncope and cardiac arrest (CA) or CA only) of the probands at the age of 5 and 10 years was higher in thede novogroup than in the familial group. Nearly half of the probands in both groups experienced CA events before diagnosis. Only 37.5% of their genotype-positive parents had symptoms; however, at least 66.7% of the genotype-positive siblings were symptomatic.ConclusionsCPVT1 probands harbouringde novo RYR2variants showed an earlier onset of symptoms than those with assured familial inheritance. Cascade screening may enable early diagnosis, risk stratification and prophylactic therapeutic intervention to prevent sudden cardiac death of probands and potential genotype-positive family members.
Correlation between Selection of Time Window for Acute Cerebral Infarction and Efficacy of Intravascular Stent Implantation
Authors: Feng Guanqing , Gong Yu 
Published: February 2022

Objective. To explore the correlation between selection of time window for acute cerebral infarction (ACI) and efficacy of intravascular stent implantation. Methods. The clinical data of 84 ACI patients treated in our hospital from March 2019 to March 2020 were selected for the retrospective analysis, all study subjects received intravascular stent implantation, and after discharge, patients were assessed by the Modified Rankin Scale (mRS) and divided into the good prognosis group (n = 46, mRS score ≤2 points) and poor prognosis group (n = 38, mRS score >2 points). The clinical data of patients in the two groups at admission underwent univariate analysis, the indicators presenting

P

< 0.05 were included in the logistic regression model, and the correlation between patients’ treatment time window and clinical effect was analyzed by multivariate logistic regression analysis and linear fitting analysis. Results. According to the multivariate logistic regression analysis, low-density lipoprotein (LDL), time window, and blood glucose level before treatment were the independent factors affecting patients’ treatment effect and were associated with the efficacy of intravascular stent implantation (r was 0.790, 0.889, and 0.672, respectively). Conclusion. LDL, time window, and blood glucose level before treatment are the important factors affecting the efficacy of intravascular stent implantation for ACI patients, among which the time window is most significantly associated with the clinical effect. Therefore, ACI patients should accept clinical treatment as early as possible.
Vítimas fatais do salazarismo: realidade e ficção em "Balada da praia dos cães: dissertação sobre um crime" (1982), de José Cardoso Pires
Authors: Rocha Denise 
Published: February 2022

O objetivo do estudo é apresentar as variadas facetas da realidade e da ficção do crime do Guincho (1960) - o assassinato do capitão Almeida Santos, um dos líderes do Golpe da Sé (1959) para derrubar a ditadura de Salazar - que abalou a opinião pública portuguesa e motivou a escrita da Balada da Praia dos Cães (1982), de José Cardoso Pires. A narrativa polifônica (Bakhtin), que será analisada segundo reflexões de Hutcheon e Todorov, evoca o ambiente de medo e violência em Lisboa, e revela a ruptura de paradigmas consagrados do romance, ao mesclar variados registros: dossiês policiais, autos e relatórios com jargões e técnicas de inquérito e de medicina legal forenses; textos e intertextos: notas de rodapé explicativas sobre a biografia de personagens e eventos históricos, notícias de jornais, panfletos etc.
Palavras-chave: Literatura portuguesa; José Cardoso Pires; Balada da Praia dos Cães; história; ficção.