bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased expression of the ATP‐gated P2X7 receptor reduces responsiveness to anti‐convulsants during status epilepticus in mice
Authors: Beamer Edward , Morgan James , Alves Mariana , Menéndez Méndez Aida , Morris Gareth , Zimmer Béla , Conte Giorgia , de Diego‐Garcia Laura , Alarcón‐Vila Cristina , Yiu Ng Nico Ka , Madden Stephen , Calzaferri Francesco , de los Ríos Cristóbal , García Antonio G. , Hamacher Michael , Dinkel Klaus , Pelegrín Pablo , Henshall David C. , Nicke Annette , Engel Tobias 
Published: December 2021

Background and PurposeRefractory status epilepticus is a clinical emergency associated with high mortality and morbidity. Increasing evidence suggests neuroinflammation contributes to the development of drug‐refractoriness during status epilepticus. Here, we have determined the contribution of the ATP‐gated P2X7 receptor, previously linked to inflammation and increased hyperexcitability, to drug‐refractory status epilepticus and its therapeutic potential.Experimental ApproachStatus epilepticus was induced via a unilateral microinjection of kainic acid into the amygdala in adult mice. Severity of status epilepticus was compared in animals with overexpressing or knock‐out of the P2X7 receptor, after inflammatory priming by pre‐injection of bacterial lipopolysaccharide (LPS) and in mice treated with P2X7 receptor‐targeting and anti‐inflammatory drugs.Key ResultsMice overexpressing P2X7 receptors were unresponsive to several anticonvulsants (lorazepam, midazolam, phenytoin and carbamazepine) during status epilepticus. P2X7 receptor expression increased in microglia during status epilepticus, at times when responses to anticonvulsants were reduced. Overexpression of P2X7 receptors induced a pro‐inflammatory phenotype in microglia during status epilepticus and the anti‐inflammatory drug minocycline restored normal responses to anticonvulsants in mice overexpressing P2X7 receptors. Pretreatment of wild‐type mice with LPS increased P2X7 receptor levels in the brain and reduced responsiveness to anticonvulsants during status epilepticus, which was overcome by either genetic deletion of P2X7 receptors or treatment with the P2X7 receptor antagonists, AFC‐5128 or ITH15004.Conclusion and ImplicationsOur results demonstrate that P2X7 receptor‐induced pro‐inflammatory effects contribute to resistance to pharmacotherapy during status epilepticus. Therapies targeting P2X7 receptors could be novel adjunctive treatments for drug‐refractory status epilepticus.
Prognostic biomarker study in patients with clinical stage I esophageal squamous cell carcinoma: JCOG0502‐A1
Authors: Oshima Kotoe , Kato Ken , Ito Yoshinori , Daiko Hiroyuki , Nozaki Isao , Nakagawa Satoru , Shibuya Yuichi , Kojima Takashi , Toh Yasushi , Okada Morihito , Hironaka Shuichi , Akiyama Yuji , Komatsu Yoshito , Maejima Kazuhiro , Nakagawa Hidewaki , Onuki Ritsuko , Nagai Momoko , Kato Mamoru , Kanato Keisuke , Kuchiba Aya , Nakamura Kenichi , Kitagawa Yuko 
Published: December 2021

AbstractWe undertook genomic analyses of Japanese patients with stage I esophageal squamous cell carcinoma (ESCC) to investigate the frequency of genomic alterations and the association with survival outcomes. Biomarker analysis was carried out for patients with clinical stage T1bN0M0 ESCC enrolled in JCOG0502 (UMIN000000551). Whole‐exome sequencing (WES) was performed using DNA extracted from formalin‐fixed, paraffin‐embedded tissue of ESCC and normal tissue or blood sample. Single nucleotide variants (SNVs), insertions/deletions (indels), and copy number alterations (CNAs) were identified. We then evaluated the associations between each gene alteration with a frequency of 10% or more and progression‐free survival (PFS) using a Cox regression model. We controlled for family‐wise errors at 0.05 using the Bonferroni method. Among the 379 patients who were enrolled in JCOG0502, 127 patients were successfully analyzed using WES. The median patient age was 63 years (interquartile range, 57‐67 years), and 78.0% of the patients ultimately underwent surgery. The 3‐year PFS probability was 76.3%. We detected 20 genes with SNVs, indels, or amplifications with a frequency of 10% or more. Genomic alterations in FGF19 showed the strongest association with PFS with a borderline level of statistical significance of P = .00252 (Bonferroni‐adjusted significance level is .0025). Genomic alterations in FGF4, MYEOV, CTTN, and ORAOV1 showed a marginal association with PFS (P < .05). These genomic alterations were all CNAs at chromosome 11q13.3. We have identified new genomic alterations associated with the poor efficacy of ESCC (T1bN0M0). These findings open avenues for the development of new potential treatments for patients with ESCC.
Building a model of cultural universality with specificity for global early childhood development
Authors: McCoy Dana Charles 
Published: December 2021

AbstractNumerous longstanding developmental theories have emphasized the important role that culture and context play in shaping young children’s skill development. Nevertheless, the field lacks explicit models describing the extent to which early childhood development may be similar (universal) versus different (specific) across cultures. In this article, I review evidence from multiple fields regarding both similarities and differences in the form, timing, and relevance of early health, learning, and psychosocial skills across cultures. I then synthesize this evidence, highlighting themes intended to build an integrated model of developmental universality with specificity that can be used to inform science and policy. I conclude with recommendations for the field, including suggestions for a more inclusive approach to studying early childhood development that breaks down established barriers among fields, stakeholders, and geographies.
Microbiota associations with inflammatory pathways in asthma
Authors: Wang Juan , Chai Jianmin , Zhang Linlin , Zhang Lijiao , Yan Wei , Sun Lina , Chen Yahong , Sun Yongchang , Zhao Jiangchao , Chang Chun 
Published: December 2021

AbstractBackgroundThe airway microbiota plays an important role in asthma pathophysiology. However, the relationship between the airway microbiota and asthma phenotypes is still poorly understood.ObjectiveWe aimed to characterize the airway microbiota in asthma patients and determine its correlation with airway inflammatory phenotypes and other phenotypic characteristics.MethodsThe microbial composition of induced sputum specimens collected from asthma patients was determined using 16S rDNA gene sequencing.ResultsPatients with asthma had a higher abundance of bacterial taxa associated with Bacteroidetes, Fusobacteria and Proteobacteria and a reduced abundance of Firmicutes and Actinobacteria compared to healthy controls. This study classified the asthma‐associated lung microbiota into three community types based on DMM models, which were defined as three pulmotypes (P1, P2 and P3). The lungs of patients with pulmotype 3 (P3) were dominated by Faecalibacterium and Bacteroides, while patients with pulmotype 1 (P1) had a greater abundance of Pasteurellaceae, Streptococcus and Rothia. P1 patients were older (p = .045) and had lower blood TGF levels (p = .028). P3 patients had fewer eosinophils (p = .016) and more neutrophils (p = .039) in induced sputa than P1 patients.ConclusionsDifferences in asthma‐associated airway microbiota pulmotypes are associated with and might influence asthma, particularly inflammatory phenotypes.
Transverse myelitis and coronavirus disease 2019 vaccine: A temporal association
Authors: da Silva Gustavo Figueiredo , da Silva Caroline Figueiredo , Oliveira Raddib Eduardo Noleto da Nobrega , Silva Felipe William Dias , Baptista João Pedro Ribeiro , Loz Sabrina Hafemann , Moro Carla Heloisa Cabral , Longo Alexandre Luiz , Ribas Gustavo da Cunha 
Published: December 2021

AbstractBackgroundTransverse myelitis (TM) is most often triggered by an autoimmune reaction due to infections and perhaps vaccines. During the current coronavirus disease 2019 (COVID‐19) pandemic, some case reports have shown a temporal association between TM and COVID‐19 vaccine. We aimed to report a case of TM with a temporal association with ChAdOx1 nCoV‐19 (AZD1222, Oxford/AstraZeneca) vaccine in a Brazilian public hospital.Case PresentationA 27‐year‐old woman experienced fever, low back pain and urinary retention 3 weeks after the first dose of the ChAdOx1 nCoV‐19 vaccine. Two days later, she experienced decreased strength of the lower limbs associated with paresthesia of the distal extremities. At the hospital, there was progression of weakness associated with anesthesia in T4‐L1. Magnetic resonance imaging findings were suggestive of demyelination and acute inflammation. Cerebrospinal fluid analysis showed monomorphonuclear pleocytosis, increased protein and decreased glucose. Gram stain, oligoclonal bands, anti‐aquaporin‐4 antibody, and screening for infectious agents and connective tissue disease were all negative. During treatment, the patient received 5‐day pulse therapy with methylprednisolone, acyclovir and 7‐day plasmapheresis. Despite all treatments, she persisted with lower limb plegia, areflexia and anesthesia at the level of T4. She was discharged with a monthly cyclophosphamide plan and outpatient follow up.ConclusionsIn the absence of other causes, the diagnosis of TM was made with evidence of a possible temporal association with ChAdOx1 nCoV‐19 vaccine. It is important to emphasize that it is a temporal association only and the benefits of vaccination continue to outweigh the risk of TM.
Comparison of the influence of light between circularly polarized and linearly polarized smartphones on dry eye symptoms and asthenopia
Authors: Mou Yujie , Shen Xiao , Yuan Kelan , Wang Xin , Fan Fangli , Wu Yaying , Wang Chunyang , Jin Xiuming 
Published: December 2021

AbstractThis paper aims to investigate the efficacy of circularly polarized light smartphones in affecting dry eye symptoms and asthenopia through a comparison with linearly polarized smartphones. One hundred twenty participants were randomly divided into four groups. Dry eye and asthenopia symptoms were evaluated using the Ocular Surface Disease Index (OSDI), Computer Vision Syndrome Scale 17 (CVSS17), Convergence Insufficiency Symptom Survey (CISS), and visual analogue scale (VAS). Objective ocular examinations were assessed by confusion flicker frequency (CFF), tear meniscus height (TMH), noninvasive break‐up time (NIBUT), conjunctiva redness, fluorescein tear break‐up time (FTBUT), corneal fluorescein staining, and the Schirmer I test. Tests were performed before and after a reading task. Subjective evaluations including the OSDI, CVSS17, and CISS were all significantly increased after reading on a linearly polarized smartphone, whereas no change was observed in the circular polarization groups in both light and dark environments. A significantly enlarged VAS was shown in all of the four groups, but a significant increase in ΔVAS only appeared in the linear polarization groups. There were significant decreases in TMH, NIBUT, conjunctiva redness, FTBUT, and CFF after reading on a linearly polarized smartphone but the circularly polarized smartphone had lesser effects on these parameters. Our study indicated that reading on linearly polarized smartphones may cause dry eye disorder, asthenopia, and ocular discomforts, whereas circularly polarized smartphones appears to minimize these adverse effects on eye dryness and visual fatigue in light and dark environments.
JAK‐inhibitors in dermatology – small molecules, big impact? Overview of the mechanism of action, previous study results and potential adverse effects
Authors: Klein Benjamin , Treudler Regina , Simon Jan C. 
Published: December 2021

SummaryNumerous chronic inflammatory skin diseases are associated with the release of proinflammatory cytokines, which act via the intracellular JAK‐STAT pathway. JAK inhibitors represent a promising, targeted therapeutic approach for cutaneous diseases. Impressive effects have been achieved with these agents in recent years. With the approval of the JAK‐inhibitors Baricitinib, Upadacitinib and Abrocitinib, new systemic therapeutic agents are now available for moderate to severe atopic dermatitis. Other diseases in which the effectiveness of these small molecules could be shown are psoriasis, chilblain lupus, dermatomyositis, vitiligo and alopecia areata. As dermatologists, we are facing a whole series of new drug approvals. In this minireview we explain the active principles of JAK inhibitors and review study results in selected inflammatory skin diseases. Finally, possible side effects and initial as well as follow‐up laboratory examinations for these drugs are discussed.
Outcomes of endoscopic submucosal dissection for colorectal neoplasms: Prospective, multicenter, cohort trial
Authors: Kobayashi Nozomu , Takeuchi Yoji , Ohata Ken , Igarashi Masahiro , Yamada Masayoshi , Kodashima Shinya , Hotta Kinichi , Harada Keita , Ikematsu Hiroaki , Uraoka Toshio , Sakamoto Naoto , Doyama Hisashi , Abe Takashi , Katagiri Atsushi , Hori Shinichiro , Michida Tomoki , Yamaguchi Takehito , Fukuzawa Masakatsu , Kiriyama Shinsuke , Fukase Kazutoshi , Murakami Yoshitaka , Ishikawa Hideki , Saito Yutaka 
Published: December 2021

ObjectivesEndoscopic mucosal resection (EMR) is the gold standard for the treatment of noninvasive large colorectal lesions, despite challenges associated with nonlifting lesions and a high rate of local recurrence. Endoscopic submucosal dissection (ESD) offers the possibility of overcoming these EMR limitations. However, a higher risk of complications and longer procedure time prevented its dissemination. As ESD now provides more stable results because of standardized techniques compared with those used earlier, this study aimed to quantify the rates of en bloc and curative resections, as well as ESD complications, in the present situation.MethodsA multicenter, large‐scale, prospective cohort trial of ESD was conducted at 20 institutions in Japan. Consecutive patients scheduled for ESD were enrolled from February 2013 to January 2015.ResultsESD was performed for 1883 patients (1965 lesions). The mean procedure time was 80.6 min; en bloc and curative resections were achieved in 1759 (97.0%) and 1640 (90.4%) lesions, respectively, in epithelial lesions ≥20 mm. Intra‐ and postprocedural perforations occurred in 51 (2.6%) and 12 (0.6%) lesions, respectively, and emergency surgery for adverse events was performed in nine patients (0.5%).ConclusionsThis trial conducted after the standardization of the ESD technique throughout Japan revealed a higher curability, shorter procedure time, and lower risk of complications than those reported previously. Considering that the target lesions of ESD are more advanced than those of EMR, ESD can be a first‐line treatment for large colorectal lesions with acceptable risk and procedure time. (Clinical Trial Registration: UMIN000010136).
Management of non‐functional pancreatic neuroendocrine tumors by endoscopic ultrasound‐guided radiofrequency ablation: Retrospective study in two tertiary centers
Authors: Marx Mariola , Godat Sébastien , Caillol Fabrice , Poizat Flora , Ratone Jean‐Philippe , Pesenti Christian , Schoepfer Alain , Hoibian Solène , Dahel Yanis , Giovannini Marc 
Published: December 2021

BackgroundRecently, there has been growing interest in investigating endoscopic ultrasound‐guided radiofrequency ablation (EUS‐RFA) for the management of small non‐functional pancreatic neuroendocrine tumors (nf pNETs).Patients and MethodsA bicentric retrospective study was performed that included patients with histologically confirmed nf pNETs who were consecutively treated by EUS‐RFA between December 2015 and March 2021 at two tertiary referral centers.ResultsIn 27 patients (mean age 65.0 years, 52% male), EUS‐RFA was successfully performed. All patients had sporadic G1 lesions (mean size 14.0 ± 4.6 mm, 7% uncinated process, 22% head, 11% body, 19% body/tail junction, and 41% tail). Overall, 9/27 lesions (33%) were cystic. The mean hospital stay was 3.2 days. Complete treatment response was confirmed in 25/27 patients (93%) on cross‐sectional imaging (mean follow‐up 15.7 ± 12.2 months, range 2–41 months). Two patients had two EUS‐RFA sessions until complete necrosis was observed. Periprocedural acute pancreatitis occurred in 4/27 (14.8%), three of them were treated by endoscopic cystogastrostomy (11.1%). One patient underwent secondary surgery. The histopathology of the resected specimen revealed 3 mm of residual tumor tissue.ConclusionEUS‐RFA seems to be a promising treatment strategy for the management of small nf pNETs with excellent efficacy. Further evidence focusing on long‐term survival, safety profile and recurrence is needed.
Multicenter prospective cohort study of adverse events associated with biliary endoscopic retrograde cholangiopancreatography: Incidence of adverse events and preventive measures for post‐endoscopic retrograde cholangiopancreatography pancreatitis
Authors: Fujita Koichi , Yazumi Shujiro , Matsumoto Hisakazu , Asada Masanori , Nebiki Hiroko , Matsumoto Kazuya , Maruo Toru , Takenaka Mamoru , Tomoda Takeshi , Onoyama Takumi , Kurita Akira , Ueki Toshiharu , Katayama Toshiro , Kawamura Takashi , Kawamoto Hirofumi ,   for the Bilio‐pancreatic Study Group of West Japan
Published: December 2021

ObjectivesThe reported incidence of adverse events (AEs) in endoscopic retrograde cholangiopancreatography (ERCP) varies between 2.5% and 14%. The aim of this study was to evaluate the incidence and severity of AEs in biliary ERCP and to specify the risk factors and preventive measures for post‐ERCP pancreatitis (PEP).MethodsPatients with biliary disease with intact papilla were prospectively enrolled at 36 hospitals between April 2017 and March 2018. The primary outcomes were the incidence and severity of AEs.ResultsA total of 16,032 ERCP procedures were performed at the 36 hospitals during the study period and 3739 patients were enrolled. The overall incidence of AEs was 10.1% and ERCP‐related mortality was 0.08%. PEP developed in 258 cases (6.9%), bleeding in 33 (0.9%), instrumental AEs in 17 (0.5%), infections in 37 (1.0%), cardiovascular AEs in eight (0.2%), pulmonary AEs in eight (0.2%), drug reaction AE in one (0.03%), pain in 15 (0.4%), and other AEs in 15 (0.4%). Multivariable analysis showed significant risk factors for PEP were: female of younger age, pancreatic guidewire‐assisted biliary cannulation, temporary guidewire insertion into the pancreatic duct, total procedure time >60 min, and post‐ERCP administration of non‐steroidal anti‐inflammatory drugs. Effective preventive measures were prophylactic pancreatic stenting (PPS) and epinephrine spraying onto the papilla.ConclusionsIn patients with intact papilla who underwent biliary ERCP, the incidence of AEs was 10.1% and the mortality was 0.08%. PPS and epinephrine spraying may prevent PEP.RegistrationThis study was registered in the University Hospital Medical Information Network (UMIN000024820).
Evidence for goal‐ and mixed evidence for false belief‐based action prediction in 2‐ to 4‐year‐old children: A large‐scale longitudinal anticipatory looking replication study
Authors: Kaltefleiter Larissa J. , Schuwerk Tobias , Wiesmann Charlotte Grosse , Kristen‐Antonow Susanne , Jarvers Irina , Sodian Beate 
Published: December 2021

AbstractUnsuccessful replication attempts of paradigms assessing children's implicit tracking of false beliefs have instigated the debate on whether or not children have an implicit understanding of false beliefs before the age of four. A novel multi‐trial anticipatory looking false belief paradigm yielded evidence of implicit false belief reasoning in 3‐ to 4‐year‐old children using a combined score of two false belief conditions (Grosse Wiesmann, C., Friederici, A. D., Singer, T., & Steinbeis, N. [2017]. Developmental Science, 20(5), e12445). The present study is a large‐scale replication attempt of this paradigm. The task was administered three times to the same sample of N = 185 children at 2, 3, and 4 years of age. Using the original stimuli, we did not replicate the original finding of above‐chance belief‐congruent looking in a combined score of two false belief conditions in either of the three age groups. Interestingly, the overall pattern of results was comparable to the original study. Post‐hoc analyses revealed, however, that children performed above chance in one false belief condition (FB1) and below chance in the other false belief condition (FB2), thus yielding mixed evidence of children's false belief‐based action predictions. Similar to the original study, participants’ performance did not change with age and was not related to children's general language skills. This study demonstrates the importance of large‐scaled replications and adds to the growing number of research questioning the validity and reliability of anticipatory looking false belief paradigms as a robust measure of children's implicit tracking of beliefs.
The ideological trends in Ali Ahmad Bakathir's Sallamat Al‐Qass
Authors: Rashed Redhwan Q. G. 
Published: December 2021

AbstractThis study examines Ali Ahmad Bakathir's unique vision in terms of the theme of love, as a subject whose treatment varies according to the ideology and philosophy of the writers. On the basis of Islamic ideals, Sallamat Al‐Qass introduces a strange relationship between an ascetic worshiper, Abdurrahman, and the woman singer, Sallama; the two fall in love and hope for reunion if not in this world, then in the hereafter. This contrasts the stories of platonic love such as Romeo and Juliet which ends tragically and shows the possibility of reconciliation between the contradictory worlds of religion and art as well. In contrast to many love stories, love in Bakathir's novel not only changes the lover's view of the world positively and reconciles it with religion, but it also refines his poetry talent and makes him more active, more humane, and God‐fearing. The reconciliation reaches the point of accepting singing as an incentive to worship. The conclusion refutes the allegations of religious hardliners who take a contrary attitude and claim that love and singing are forbidden. Bakathir himself may have had the same experience encountered by his character Abdurrahman, as his novel seems to reflect the experience of such emotions from an Islamic perspective.
Danish university governance reforms: Internationalisation and de‐internationalisation
Authors: Wright Susan 
Published: December 2021

AbstractThis article analyses the process of reforming the governance of Danish universities, from an anthropological perspective. Observers saw that the assemblage of steering concepts, tools and mechanisms in the 2003 Danish university law could be articulated in two contrary ways: one would make the university into apower forcewith ideas that exceeded the government's imagining of the future; the other turned the university into a tightly steered service provider, quick to respond to changes in political priorities. Initially, the government took the first approach in promoting the internationalisation of research and education. Its strategy provided a framework of opportunities that university leaders and academics used voluntarily to fulfil their own visions for their institution or discipline. In 2018, the government's priority suddenly shifted to de‐internationalisation of Danish higher education. To achieve this, it rearticulated the same steering concepts, tools and mechanisms to impose cuts to English‐medium courses throughcommando‐style steering, and academics and students were disenfranchised. The internationalisation strategy first mobilised the capacities of the university as apower force. When the government decided to de‐internationalise, it turned the same steering assemblage into a chain of command that made the university respond quickly to a changed political priority.