bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of novel ALKATI with ALK immunohistochemistry and clinical outcomes in metastatic melanoma
Authors: Shah Kabeer K , Neff Jadee L , Erickson Lori A , Jackson Rory A , Jenkins Sarah M , Mansfield Aaron S , Moser Justin C , Harris Antoneicka L , Copland John A , Halling Kevin C , Flotte Thomas J 
Published: June 2020

AimsRecently, a novel isoform of anaplastic lymphoma kinase, with alternative transcription initiation (ALKATI), has been described in melanoma and is susceptible to targeted ALK‐inhibitor therapy. Clinical outcomes of patients with ALKATI mutated melanoma as well as correlation with immunohistochemical (IHC) methods have not yet been described.Methods and resultsClinicopathological characteristics were abstracted for 324 patients with metastatic melanoma (MM). IHC, fluorescence in‐situ hybridisation and RNA‐based digital molecular analysis assays were performed on archival tissue from 173 stage III and 192 stage IV tumours. ALKATI was identified in 12.7 and 4.8% stage III and IV tumours, respectively. Discrete presentations of the ALKATI are seen: isolated ALKATI (n = 20) and mixed ALKATI (combined ALKATI and ALKWT; n = 7). Isolated ALKWT expression (n = 4) was seen with no ALK fusions. Stage III patients showed improved survival with ALKATI expression compared to those with ALKWT or no expression [5‐year survival 80, 95% confidence interval (CI) = 57–100% versus 43%, 95% CI = 34–55%, P = 0.013]. Clinicopathological characteristics were not statistically significant. Strong diffuse cytoplasmic staining of ALK IHC (n = 12) has a sensitivity of 52.2%, specificity 100%, PPV of 100% and NPV of 92.5% of detecting isolated ALKATI.ConclusionPresence of ALKATI is a good prognostic indicator in MM. ALK IHC and digital molecular analysis can be incorporated into MM evaluation to identify patients with ALKATI for targeted therapy.
Automated separation of tail fraction for fruit distillates by means of in‐line conductivity measurement
Authors: Liebminger Andreas , Holstein Markus , Dietrich Volker , Goessinger Manfred 
Published: June 2020

SummaryThe distillation cuts between head, heart and tail fraction of a fruit distillate are still done in an empirical fashion, based on the distiller’s sensorial experience. There has been an unmet need for a long time to provide an objective method for determining the point of tails independent of fruit type and distillation technique. In this study, the authors provide a new method for separating the tail robustly from the heart fraction. For the first time, this is based on an in‐line measurement of conductivity together with a suited algorithm for differentiating the conductivity increase before and after the point of tails. The method has been validated with three different fruit mashes of different sugar content, distilled applying different levels of rectification due to different settings of the dephlegmator of the still. Verification with sensory analysis confirmed the validity of the method.
Reconciling protective and pathogenic roles of the NLRP3 inflammasome in leishmaniasis
Authors: Harrington Valerie , Gurung Prajwal 
Published: June 2020

AbstractLeishmaniasis is a global health problem that affects more than 2 billion people worldwide. Recent advances in research have demonstrated critical roles for cytoplasmic sensors and inflammasomes during Leishmania spp. infection and pathogenesis. Specifically, several studies have focused on the role of nod‐like receptor family, pyrin domain‐containing protein 3 (NLRP3) inflammasome and inflammasome‐associated cytokines IL‐1β and IL‐18 in leishmaniasis. Despite these studies, our understanding of the priming and activation events that lead to NLRP3 inflammasome activation during Leishmania spp. infection is limited. Furthermore, whether NLRP3 plays a protective or pathogenic role during Leishmania spp. infection is far from resolved, with some studies showing a protective role and others showing a pathogenic role. In this review, we performed a critical review of the literature to provide a current update on priming and activating signals required for NLRP3 inflammasome activation during Leishmania spp. infection. Finally, we provide a thorough review of the literature to reconcile differences in the observed protective vs pathogenic roles of the NLRP3 inflammasome during Leishmania spp. infection.
Control of foreign Ag‐specific Ab responses by Treg and Tfr
Authors: Wing James B. , Lim Ee Lyn , Sakaguchi Shimon 
Published: June 2020

AbstractRegulatory T cells (Tregs) expressing the transcription factor Foxp3 play a critical role in the control of immune homeostasis including the regulation of humoral immunity. Recently, it has become clear that a specialized subset of Tregs, T‐follicular regulatory cells (Tfr), have a particular role in the control of T‐follicular helper (Tfh) cell‐driven germinal center (GC) responses. Following similar differentiation signals as received by Tfh, Tfr gain expression of characteristic chemokine receptors and transcription factors such as CXCR5 and BCL6 allowing them to travel to the B‐cell follicle and deliver in situ suppression. It seems clear that Tfr are critical for the prevention of autoimmune antibody induction. However, their role in the control of foreign antigen‐specific antibody responses appears more complex with various reports demonstrating either increased or decreased antigen‐specific antibody responses following inhibition of Tfr function. Due to their recent discovery, our understanding of Tfr formation and function still has many gaps. In this review, we discuss our current knowledge of both Tregs and Tfr in the context of humoral immunity and how these cells might be manipulated in order to better control vaccine responses.
Nuclear innate sensors for nucleic acids in immunity and inflammation
Authors: Lin Hongyu , Cao Xuetao 
Published: June 2020

AbstractInnate sensors recognize pathogen‐associated molecular patterns (PAMPs) or damage‐associated molecular patterns (DAMPs) to initiate innate immune response by activating downstream signaling. These evolutionarily conserved innate sensors usually locate in the plasma membrane or cytoplasm. However, the nucleus‐localized innate sensors are recently found to detect pathogenic nucleic acids for initiating innate response, demonstrating a complicated crosstalk with cytoplasmic sensors and signaling molecules to form an elaborate tiered innate signaling network between nucleus and cytoplasm. Furthermore, these nuclear innate sensors evolve varied mechanisms for discriminating self from non‐self nucleic acids to maintain immune homeostasis and avoid autoinflammatory immune response. In this review, we summarize the recent findings on the identification of nuclear innate sensors for nucleic acids, such as hnRNPA2B1, IFI16, SAFA, and their roles in host defense and inflammatory response.
What drives the attentional bias for fearful faces? An eye‐tracking investigation of 7‐month‐old infants’ visual scanning patterns
Authors: Segal Shira C. , Moulson Margaret C. 
Published: June 2020

AbstractSeven‐month‐old infants display a robust attentional bias for fearful faces; however, the mechanisms driving this bias remain unclear. The objective of the current study was to replicate the attentional bias for fearful faces and to investigate how infants’ online scanning patterns relate to this preference. Infants’ visual scanning patterns toward fearful and happy faces were captured using eye tracking in a paired‐preference task, specifically exploring if the fear preference is driven by increased attention to particular facial features. Infants allocated increased attention toward the fearful face compared to the happy face overall, thus successfully replicating the attentional bias, and greater attention toward the fearful eyes was associated with a greater magnitude of the fear preference. The current findings suggest that the fearful eyes are a salient facial feature in capturing infants’ attention toward the fearful face and that increased scanning of the fearful eyes may be one mechanism driving the overall fear preference. In addition, scanning patterns, and attention to critical features specifically, are highlighted as a strategy for examining the mechanisms underlying the development of emotion recognition abilities in infancy.
Clinical phase II and III studies of an AS03‐adjuvanted H5N1 influenza vaccine produced in an EB66® cell culture platform
Authors: Endo Masafumi , Tanishima Mitsuyoshi , Ibaragi Kayo , Hayashida Kenshi , Fukuda Tadashi , Tanabe Tetsuro , Naruse Takeshi , Kino Yoichiro , Ueda Kohji 
Published: June 2020

AbstractBackgroundWe have developed an AS03‐adjuvanted H5N1 influenza vaccine produced in an EB66® cell culture platform (KD‐295).ObjectivesIn accordance with Japanese guidelines for development of pandemic prototype vaccines, the phase II study was conducted in a double‐blind, randomized, parallel‐group comparison study and the phase III study was conducted in an open‐label, non‐randomized, uncontrolled study.MethodsHealthy adult volunteers aged 20 ‐ 64 years enrolled in the phase II and III studies (N = 248 and N = 369) received KD‐295 intramuscularly twice with a 21‐day interval. After administration, immune response and adverse events were evaluated. In the phase II study, four different vaccine formulations were compared: MA (3.75 μg hemagglutinin [HA] antigen + AS03 adjuvant system), MB (3.75 μg HA + 1/2AS03), HA (7.5 μg HA + AS03), and HB (7.5 μg HA + 1/2AS03). In the phase III study, the MA formulation was further evaluated.ResultsIn the phase II study, all four vaccine formulations were well‐tolerated and no SAE related to vaccination were observed. The MA formulation was slightly more immunogenic and less reactogenic among the vaccine formulations. Therefore, the MA formulation was selected for the phase III study, and it was well‐tolerated and no serious adverse drug reactions were observed. The vaccine fulfilled the three immunogenicity criteria described in the Japanese guidelines.ConclusionsThese data indicate that the MA formulation of KD‐295 was well‐tolerated and highly immunogenic and it can be considered a useful pandemic and pre‐pandemic influenza vaccine.
Becoming a boy in a homoparental situation: a psychoanalytic approach
Authors: Ducousso‐Lacaze Alain , Grihom Marie‐José , Atani Torasso Louise 
Published: June 2020

SummaryThis article examines a case of gay parenting analysed in the context of a collective, interdisciplinary research project funded by the French National Research Agency (Agence Nationale de la Recherche). Its authors use a clinical psychoanalytical approach, applying this methodology to the single case study of a lesbian couple and their son, who was eight and half years old at the time of the research project. The clinical data were gathered using several techniques: interviews with the parents and the completion of a family tree, a projective test, and a game with the child. The analysis, drawing on psychoanalytical conceptual frameworks, describes how belonging and difference are both constructed and transmitted along family lines. Data obtained relating to the mothers reveal how the relationship within the couple is articulated with Oedipal configurations, ancestral history and representations of the sperm donor that interact with intrapsychic conflicts and the differences they promote, including those along the lines of gender. Analysis of the data produced with the child suggest that he uses these situations to create a representation of his place within the successive generations in his family, his own gender identity and his fantasies spun out around the identity of the sperm donor.
When does gender diversity enhance team performance? The dual need for visionary leadership and team tenure
Authors: Kelemen Thomas K. , Matthews Samuel H. , Zhang Xin‐an , Bradley Bret H. , Liu Huihua 
Published: June 2020

AbstractTeams in organizations are becoming more gender diverse as women continue to participate more in the workforce than ever before. Prior theory and research indicate that the characteristics of the team influence whether gender diversity in a team is an asset or a detriment. As such, this research explores a contingency model of the relation between gender diversity and team performance and looks to understand conditions that make this relation positive or negative. Specifically, we examine how leader vision communication (i.e., visionary leadership) affects the relation between gender diversity and team performance. Results from a sample of 595 full‐time employees across 106 teams in China indicate that leader vision communication moderates the relation between gender diversity and team performance such that when leader vision communication is low gender diversity decreases team performance and when leader vision communication is high gender diversity has no significant relation with team performance. We also test whether team tenure changes this relationship. Our results suggest that gender diversity improves team performance when both leader vision communication and team tenure are high. The findings in our sample demonstrate that gender diversity can help teams enhance performance, but only when the conditions are right for gender‐diverse teams to flourish.
A novel prognostic signature of immune‐related genes for patients with colorectal cancer
Authors: Wang Jun , Yu Shaojun , Chen Guofeng , Kang Muxing , Jin Xiaoli , Huang Yi , Lin Lele , Wu Dan , Wang Lie , Chen Jian 
Published: June 2020

AbstractColorectal cancer (CRC) is one of the most commonly diagnosed cancers with an estimated 1.8 million new cases worldwide and associated with high mortality rates of 881 000 CRC‐related deaths in 2018. Screening programs and new therapies have only marginally improved the survival of CRC patients. Immune‐related genes (IRGs) have attracted attention in recent years as therapeutic targets. The aim of this study was to identify an immune‐related prognostic signature for CRC. To this end, we combined gene expression and clinical data from the CRC data sets of The Cancer Genome Atlas (TCGA) into an integrated immune landscape profile. We identified a total of 476 IRGs that were differentially expressed in CRC vs normal tissues, of which 18 were survival related according to univariate Cox analysis. Stepwise multivariate Cox proportional hazards analysis established an immune‐related prognostic signature consisting of SLC10A2, FGF2, CCL28, NDRG1, ESM1, UCN, UTS2 and TRDC. The predictive ability of this signature for 3‐ and 5‐year overall survival was determined using receiver operating characteristics (ROC), and the respective areas under the curve (AUC) were 79.2% and 76.6%. The signature showed moderate predictive accuracy in the validation and GSE38832 data sets as well. Furthermore, the 8‐IRG signature correlated significantly with tumour stage, invasion, lymph node metastasis and distant metastasis by univariate Cox analysis, and was established an independent prognostic factor by multivariate Cox regression analysis for CRC. Gene set enrichment analysis (GSEA) revealed a relationship between the IRG prognostic signature and various biological pathways. Focal adhesions and ECM‐receptor interactions were positively correlated with the risk scores, while cytosolic DNA sensing and metabolism‐related pathways were negatively correlated. Finally, the bioinformatics results were validated by real‐time RT‑qPCR. In conclusion, we identified and validated a novel, immune‐related prognostic signature for patients with CRC, and this signature reflects the dysregulated tumour immune microenvironment and has a potential for better CRC patient management.
Small but significant: Insights and new perspectives of exosomes in cardiovascular disease
Authors: Zhang Jianchao , Cui Xiaolin , Guo Jiacheng , Cao Chang , Zhang Zenglei , Wang Bo , Zhang Li , Shen Deliang , Lim Khoon , Woodfield Tim , Tang Junnan , Zhang Jinying 
Published: June 2020

AbstractCardiovascular diseases (CVDs) are a major health problem worldwide, and health professionals are still actively seeking new and effective approaches for CVDs treatment. Presently, extracellular vesicles, particularly exosomes, have gained its popularity for CVDs treatment because of their function as messengers for inter‐ and extra‐cellular communications to promote cellular functions in cardiovascular system. However, as a newly developed field, researchers are still trying to fully understand the role of exosomes, and their mechanism in mediating cardiac repair process. Therefore, a comprehensive review of this topic can be timely and favourable. In this review, we summarized the basic biogenesis and characterization of exosomes and then further extended the focus on the circulating exosomes in cellular communication and stem cell‐derived exosomes in cardiac disease treatment. In addition, we covered interactions between the heart and other organs through exosomes, leading to the diagnostic characteristics of exosomes in CVDs. Future perspectives and limitations of exosomes in CVDs were also discussed with a special focus on exploring the potential delivery routes, targeting the injured tissue and engineering novel exosomes, as well as its potential as one novel target in the metabolism‐related puzzle.
Calcitonin inhibits intervertebral disc degeneration by regulating protein kinase C
Authors: Ge Jun , Cheng Xiaoqiang , Yan Qi , Wu Cenhao , Wang Yingjie , Yu Hao , Yang Huilin , Zhou Feng , Zou Jun 
Published: June 2020

AbstractIntervertebral disc degeneration (IVDD) is the most critical factor that causes low back pain. Molecular biotherapy is a fundamental strategy for IVDD treatment. Calcitonin can promote the proliferation of chondrocytes, stimulate the synthesis of matrix and prevent cartilage degeneration. However, its effect and the underlying mechanism for IVDD have not been fully revealed. Chondrogenic specific matrix components’ mRNA expression of nucleus pulposus cell (NPC) was determined by qPCR. Protein expression of NPC matrix components and protein kinase C was determined by Western blotting. A rat caudal intervertebral disc degeneration model was established and tested for calcitonin in vivo. IL‐1 induced NPC change via decreasing protein kinase C (PKC)‐ε phosphorylation, while increasing PKC‐δ phosphorylation. Calcitonin treatment could prevent or reverse IL‐1‐induced cellular change on PKC signalling associated with degeneration. The positive effect of calcitonin on IVDD in vivo was verified on a rat caudal model. In summary, this study, for the first time, elucidated the important role of calcitonin in the regulation of matrix components in the nucleus of the intervertebral disc. Calcitonin can delay degeneration of the intervertebral disc nucleus by activating the PKC‐ε pathway and inhibiting the PKC‐δ pathway.
Genomic profiling of late‐onset basal cell carcinomas from two brothers with nevoid basal cell carcinoma syndrome
Authors: Hasan Ali O. , Yurchenko A.A. , Pavlova O. , Sartori A. , Bomze D. , Higgins R. , Ring S.S. , Hartmann F. , Bühler D. , Fritzsche F.R. , Jochum W. , Navarini A.A. , Kim A. , French L.E. , Dermitzakis E. , Christiano A.M. , Hohl D. , Bickers D.R. , Nikolaev S.I. , Flatz L. 
Published: June 2020

AbstractBackgroundNevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant genetic disorder. It is commonly caused by mutations in PTCH1 and chiefly characterized by multiple basal cell carcinomas (BCCs) developing prior to the age of 30 years. In rare cases, NBCCS presents with a late onset of BCC development.ObjectiveTo investigate BCC tumorigenesis in two brothers, who showed characteristic features of NBCCS but developed their first BCCs only after the age of 40 years. Two other siblings did not show signs of NBCCS.ResultsWe obtained blood samples from four siblings and nine BCCs from the two brothers with NBCCS. Whole exome sequencing and RNA sequencing revealed loss of heterozygosity (LOH) of PTCH1 in eight out of nine tumours that consistently involved the same haplotype on chromosome 9. This haplotype contained a germinal splice site mutation in PTCH1 (NM_001083605:exon9:c.763‐6C>A). Analysis of germline DNA confirmed segregation of this mutation with the disease. All BCCs harboured additional somatic loss‐of‐function (LoF) mutations in the remaining PTCH1 allele which are not typically seen in other cases of NBCCS. This suggests a hypomorphic nature of the germinal PTCH1 mutation in this family. Furthermore, all BCCs had a similar tumour mutational burden compared to BCCs of unrelated NBCCS patients while harbouring a higher number of damaging PTCH1 mutations.ConclusionsOur data suggest that a sequence of three genetic hits leads to the late development of BCCs in two brothers with NBCCS: a hypomorphic germline mutation, followed by somatic LOH and additional mutations that complete PTCH1 inactivation. These genetic events are in line with the late occurrence of the first BCC and with the higher number of damaging PTCH1 mutations compared to usual cases of NBCCS.
Type locality and species identity of Pareuchiloglanis sinensis (Hora & Silas) with a description of a new species of the genus from the upper Yangtze River basin in southern China
Authors: Li Xu , Dao Wei , Zhou Wei 
Published: June 2020

AbstractThe genus Pareuchiloglanis, distributed in the Salween, Mekong, Red, Pearl and Yangtze River basins in China, Laos, Myanmar and Vietnam, consists of 20 valid species and 5 uncertain species. This study provided a taxonomic revision to Pareuchiloglanis occurring in the Yangtze River. According to the results of a morphological comparison, the type locality of Pareuchiloglanis sinensis was updated to the Nanpan‐jiang (the upper Pearl River) basin; five species were identified in Pareuchiloglanis from the Yangtze River basin. Specimens formerly identified as Pareuchiloglanis sinensis from this basin were described as a new species, Pareuchiloglanis chui sp. nov. Moreover, Pareuchiloglanis tianquanensis was synonymized with Pareuchiloglanis sichuanensis. This study provided a key to these two species and three others (Pareuchiloglanis anteanalis, Pareuchiloglanis hupingshanensis and Pareuchiloglanis robusta) from the Yangtze River basin, including information about their geographical distribution. These findings provide an insight into the evolution, distribution and taxonomy of this genus for future studies.