bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single‐cell transcriptomic analysis reveals circadian rhythm disruption associated with poor prognosis and drug‐resistance in lung adenocarcinoma
Authors: He Lei , Fan Yixian , Zhang Yue , Tu Tongtao , Zhang Quan , Yuan Fahu , Cheng Chao 
Published: April 2022

AbstractCircadian rhythm disruption (CRD) represents a major contributor to tumor proliferation. Nonetheless, the role of CRD in the clinical prediction of cancer outcomes has not been well studied. In this study, we developed a computational algorithm, which was implemented in an open‐source R package CRDscore, to define the intratumoral status of circadian disruption in three representative single‐cell RNA‐seq data sets of lung adenocarcinoma. We found that the malignant cells with high CRDscore were characterized by activation of glycolysis and epithelial–mesenchymal transition pathways. Furthermore, cell communication analysis indicated that CRD played a pivotal role in T cell exhaustion, which may be responsible for the poor prognosis of the malignancy. We then validated the findings with public bulk transcriptome datasets involving 22 cancer types. Cox regression analysis revealed that the CRDscore was a valuable prognostic biomarker. A model containing 23 circadian‐related genes performed well in predicting immunotherapeutic outcomes in 14 independent cohorts. Importantly, decreased CRDscore was detect by RNA sequencing on H1299 cells with melatonin treatment. Meanwhile, the cells downregulated the expression level of SNAIL and TWIST, which contributed to an invasive phenotype. In conclusion, this study provides a novel computational framework for characterizing CRD status using single‐cell transcriptomic data and further confirmed the molecular mechanisms underlying metabolic reprogramming and T cell exhaustion under CRD. The better understanding of the mechanisms may provide new possibilities for incorporating “anticancer approaches based on circadian clocks” into the treatment protocols of precision medicine.
Periodontitis exacerbates endothelial dysfunctions partly via endothelial‐mesenchymal transition in streptozotocin‐induced diabetes rats
Authors: Yang Shurong , Cheng Rui , Xu Xiaojiang , Zhang Ran , Zhao Yong , Shi Xuexue , Gao Jinhua , Yu Feiyan , Ren Xiuyun 
Published: April 2022

AbstractObjectivesPeriodontal infections are related to the expansion of diabetes cardiovascular problems. However, the pathological process and probable mechanism remain unexplained. This study investigated the impact of periodontitis on streptozotocin (STZ)‐induced diabetes rats' carotid artery.MethodsWe randomized 24 Sprague‐Dawley (SD) rats into four groups: control, chronic periodontitis (CP), diabetes mellitus (DM), and DM +CP groups. Fasting blood glucose (FBG) and hemoglobin A1c (HBA1c) were measured to verify the establishment of the DM model. After euthanasia, the maxillary was collected for further studies like hematoxylin‐eosin (HE), Masson staining, and micro‐computed tomography (micro‐CT) analysis. Immunofluorescence (IF) staining was used to detect endothelial‐mesenchymal transition (EndMT)‐related markers in carotid artery wall. We further used ELISA and quantitative real‐time PCR to investigate the effect of high glucose (HG) and Porphyromonas gingivalis lipopolysaccharide (P.g‐LPS) on human umbilical vein endothelial cells (HUVECs).ResultsCompared with DM and CP groups, bone resorption and pathological changes of the vascular wall were the most serious in the DM+CP group. The vascular wall of the DM+CP group had a higher level of interleukin (IL)‐6 and vascular cell adhesion molecule 1 (VCAM‐1). The carotid artery vascular wall of the DM+CP group contained more cells that expressed both mesenchymal and endothelial cell markers, along with elevated transcription factor levels. Furthermore, P.g‐LPS and HG upregulated the inflammatory cytokines expression and caused phenotypic changes of HUVECs in vitro.ConclusionPeriodontitis exacerbates endothelial dysfunctions partly via endothelial‐mesenchymal transition in STZ‐induced diabetes rats.
Introduction: Investigating Explicit L2 Grammar Instruction Through Multiple Theoretical and Methodological Lenses
Authors: Toth Paul D. 
Published: April 2022

AbstractThe articles in this special issue apply a variety of theoretical and methodological perspectives to quantitative and qualitative data gathered in eight third‐year, intermediate second‐language (L2) Spanish classes at three U.S. high schools (N = 195). The goal of this research was to document grammatical development through two forms of explicit instruction on the pronoun se: one involving deductive rule presentations, and the other involving an inductive “co‐construction” of grammatical rules with learners (Adair‐Hauck et al., 2005). After reviewing cognitive and social approaches to explicit instruction, I present the context and procedures for data gathering, followed by an overview of the main findings in each article. While quantitative results suggest a somewhat stronger performance for the deductive group, qualitative evidence suggests a more challenging task for teachers implementing co‐construction. I conclude emphasizing the value of high‐quality explicit instruction to L2 development and the importance of teachers in making that happen.
Parity, moral options, and the weights of reasons
Authors: Tucker Chris 
Published: April 2022

AbstractThe (moral) permissibility of an act is determined by the relative weights of reasons, or so I assume. But how many weights does a reason have? Weight Monism is the idea that reasons have a single weight value. There is just the weight of reasons. The simplest versions hold that the weight of each reason is either weightier than, less weighty than, or equal to every other reason. We'll see that this simple view leads to paradox in at least two ways. We must complicate the picture somehow. I consider two candidate complications. The first, Parity Monism, is inspired by Ruth Chang's suggestion that parity is a fourth comparative beyond the traditional three (>, <, =). This view complicates the single weight relation by allowing that the weights of reasons can be on a par. Unfortunately, Parity Monism resolves only one of the two paradoxes that afflict simple versions of Weight Monism. To resolve both paradoxes, we need our second candidate complication, Weight Pluralism. This view holds that reasons have at least two weight values (e.g., justifying weight and requiring weight) and these two values aren't always equivalent. Parity is no substitute for Pluralism.
Fourth‐Generation Ceramic‐on‐Ceramic THA in Patients with Ankylosing Spondylitis: A Minimum 10‐Year Follow‐Up
Authors: Li Liangliang , Fu Jun , Xu Chi , Ni Ming , Chai Wei , Hao Libo , Zhou Yonggang , Chen Jiying 
Published: April 2022

AbstractObjectiveTo report the long‐term outcomes of total hip arthroplasty (THA) with fourth‐generation ceramic‐on‐ceramic (CoC) bearing in patients with ankylosing spondylitis (AS).MethodsWe retrospectively identified 180 primary THAs performed in 110 patients with AS, including 100 (90.9%) men and 10 women (9.1%), from 2009 to 2011.The mean age of the patients at surgery was 33 years (range, 16 to 65 years). Cementless prostheses with fourth‐generation CoC bearings were used in all patients. Survivorship of the implants and postoperative complications were calculated. Functional improvement was assessed by the hip flexion‐extension range of motion (ROM) and Harris hip score (HHS). A special noise assessment questionnaire was performed at the last follow‐up. The cumulative incidence of noise was calculated by the Kaplan–Meier method with 95% confidence intervals (CIs). Clinical characteristics and functional outcomes were compared in the hips with noise to those without noise.ResultsThe mean follow‐up was 11 years (range, 10 to 12 years), and survivorship of the implants was 99.4% at the most recent follow‐up. The complications included dislocation (one hip, 0.6%), periprosthetic joint infection (one hip, 0.6%), mild to moderate pain (five hips, 2.8%), heterotopic ossification (12 hips, 6.7%), and noise (52 hips, 28.9%). The flexion‐extension ROM improved significantly with a median from 10° (range, 0 ~ 130°) to 100° (30 ~ 130°) after THA (p < 0.001), and the HHS increased significantly from 41 ± 20 to 90 ± 8 (p < 0.001). The cumulative incidence of noise at 0.5, 5, and 10 years was 6.1% (95% CI, 2.6 ~ 9.6), 16.7% (95% CI, 11.2 ~ 22.1), and 28.9% (95% CI, 22.2 ~ 35.5), respectively, and that of squeaking at 0.5, 5, and 10 years was 4.4% (95% CI, 1.4 ~ 7.4), 13.3% (95% CI, 8.4 ~ 18.3), and 23.9% (95% CI, 17.6 ~ 30.1), respectively. None of the patients with noise generation in the hip reported it affecting daily activities or causing dissatisfaction. No differences in age, sex, BMI, disease duration, bilateral THA, the frequency of bony ankylosis, the proportion of using a 36‐mm‐diameter femoral head, pre/postoperative flexion‐extension ROM, or pre/postoperative HHS were found between hips with noise and those without noise (p > 0.05).ConclusionTHAs with fourth‐generation CoC bearings exhibit excellent long‐term survival and clinical outcomes in patients with AS, with a very low dislocation rate. The incidence of noise associated with CoC bearings in THA performed in patients increases over time, but it does not affect postoperative hip function or daily activities.
IgE mediated legume allergy in east Mediterranean children: A reflection of multiple food allergies
Authors: Soyak Aytekin Elif , Unsal Hilal , Sahiner Umit Murat , Soyer Ozge , Sekerel Bulent Enis 
Published: April 2022

AbstractBackgroundLegumes are nutritionally valuable as an inexpensive protein source, but may cause severe allergic reactions. This study aimed to identify the characteristics of legume allergies (LAs) in Turkish children.MethodsA total of 87 children (4.9 (3.1–7.0) years) with LAs confirmed by either oral food challenge (OFC) or consistent history were reviewed.ResultsThe median age of onset was 19 (12–38) months. The most frequent LA was lentil (n = 57, 66%), followed by peanut (n = 53, 61%), chickpea (n = 24, 28%), pea (n = 21, 24%), bean (n = 7, 8%), and soybean (n = 1, 1%). From these, it was observed that 60% had multilegume (≥2) allergies and the age of onset occurred earlier compared with the single LA subgroup (18 (11–30) vs. 28 (17–42) months, p = .042). Single LA was present in peanut (51%) and lentil (16%) allergies, but not chickpea, pea, and bean. Fifteen patients had tolerated lentils before their first allergic reaction. The majority of children with LA (91.9%) were allergic to multiple foods including tree nuts (71%), hen's egg (66%), and cow's milk (49%). Seventy‐eight patients (89.7%) also presented with atopic comorbidities concerning atopic dermatitis (70%), asthma (40%), and allergic rhinitis (30%). Patients with anaphylactic type of reaction (20%) had higher frequency of aeroallergen sensitization (p = .001). Lip dose challenge with legume paste predicted the result of OFC with a diagnostic accuracy of 81.82% and a positive likelihood ratio of 10.8.ConclusionIn Turkey, LA is a reflection of multiple food allergies and the presence of allergy to a least frequently encountered legume is a sign of multiple LA.
Dexmedetomidine as a sole sedative for procedural sedation in preterm and neonate infants: A retrospective analysis
Authors: Leister Nicolas , Yücetepe Sirin , Ulrichs Christoph , Pietsch Steffi , Schink Ullrich , Kilian Janine , Menzel Christoph , Trieschmann Uwe 
Published: April 2022

AbstractBackgroundMany different sedation concepts for magnetic resonance imaging have been described for prematurely and term‐born infants, ranging from “no sedation” to general anesthesia. Dexmedetomidine is an alpha‐2 receptor agonist that is frequently used to sedate older children, because the anesthesiologist can easily adjust sedation depth, the patient maintains spontaneous breathing, and awakens rapidly afterwards.AimsThe present study evaluates whether dexmedetomidine could safely be used as the sole sedative for prematurely and term‐born infants less than 60 weeks postconceptional age undergoing diagnostic procedures.MethodsWe performed a retrospective monocentric analysis of n = 39 prematurely and term‐born infants (<60 weeks postconceptional age or a body weight <5 kg) who were sedated with dexmedetomidine for an MRI at a German university hospital from August 2016 to November 2018.ResultsSuccessful imaging was achieved in all cases. The median initial bolus of dexmedetomidine administered over 10 min was 1.39 μg kg−1 body weight (range 0.34–3.64 μg kg−1), followed with a continuous infusion at a median rate of 1.00 μg kg−1 h−1 (range 0.5–3.5 μg kg−1 h−1); however, 3 patients (7%) needed some additional sedation (ketamine or propofol). All patients, including 10 infants who had previously required respiratory support, underwent the procedure without any relevant desaturation or apnea. Bradycardia was observed in up to 15 out of 39 cases (38.5%), but only four (10.3% in total and 26.7% of bradycardia) required atropine.ConclusionsThese results indicate that dexmedetomidine can be safely used for procedural sedation in the high‐risk cohort of prematurely and term‐born infants less than 60 weeks postconceptional age. Apnea during procedural sedation and subsequent stay in the recovery room is avoided, but bradycardia remains a relevant risk that may require treatment.
Gallstones in patients with severe motor and intellectual disability
Authors: Zuo Shogo , Sawai Toshio , Kanehiro Hiromichi , Kuroda Yasuhiro , Sho Masayuki 
Published: April 2022

AbstractBackgroundAsymptomatic gallbladder stones may be detected with ultrasound; some gallstones produce symptomatic diseases, such as cholecystitis, cholangitis, or pancreatitis. Identifying the clinical features of symptomatic gallstones may help prevent severe complications by providing intervention for asymptomatic gallstones. We aimed to investigate risk factors associated with developing symptomatic disease in pediatric patients with severe motor and intellectual disabilities (SMID).MethodsThis retrospective study enrolled 30 patients with SMID who were treated at the Nara Medical University between March 2016 and March 2019. We examined the prevalence of gallstones, and the rate at which associated symptoms of gallstones were observed in patients. Furthermore, we compared the clinical features of patients with and without gallstones.ResultsAmong 30 patients with SMID, 7 (23%) had gallstones, with 6 (86%) of them being symptomatic: 3 patients had acute pancreatitis and 3 had cholecystitis or cholangitis. Among 23 patients without gallstones, 2 had acute pancreatitis and 2 had biliary sludge. Patients with gallstones had significantly lower daily calorie intake than those without gallstones (P = 0.042). Furthermore, the incidence of gallstones was higher in patients who received total parenteral nutrition than in those who did not (P = 0.031). Comparative analysis between symptomatic and asymptomatic patients was not performed because almost all cases were symptomatic.ConclusionGallstones were detected in 23% of patients with SMID. The gallstones were symptomatic at a very high rate. Considering this fact, patients with SMID should be surveyed for gallstones; careful management may be needed in such patients.
Interaction of blood calcium with luteal activity, energy metabolites and somatic cells count in post‐partum dairy cows
Authors: Shoukat Farhad , Khan Rifat Ullah , De Marzo Davide , Mazzei Domenico , Laudadio Vito , Tufarelli Vincenzo 
Published: April 2022

AbstractThe aim of the research was to assess whether there was a link between serum calcium (Ca) after calving and serum progesterone, milk somatic cells count and Ca, and other blood metabolites in Achai and crossbred cows. Based on blood calcium level shortly after calving, thirty cows from both breeds were divided into a moderate group (≤10.0 mg/dl of Ca) and a high group (>10.0 mg/dl of Ca), with samples collected at 0, 7, 14, 21, 28 and 35 days post‐partum, respectively. On day 35 of the post‐partum, crossbred and Achai cows with high blood Ca recorded significantly (p < .01) higher serum progesterone, glucose, triglyceride and milk Ca compared with moderate blood Ca group; however, serum cholesterol was significantly (p < .01) higher in both breeds under high blood Ca. Incidence of subclinical mastitis was significantly (p < .01) higher in crossbred and Achai cows under high blood Ca. The results showed that blood progesterone (OR=2.095), glucose (OR=1.024), triglyceride (OR=4.571), cholesterol (OR=1.111) and milk Ca (OR=1.141) resulted in a greater concentration in crossbred compared to Achai cows. A significant (p < .01) correlation was found between blood Ca and other blood metabolites (progesterone, glucose, triglyceride and cholesterol) in both breeds. In conclusion, greater serum Ca concentration after calving is associated with greater serum progesterone, glucose, triglyceride and milk Ca in crossbred cows; however, the incidence of subclinical mastitis increased.
Discrimination of tectonic influence from volcano‐sedimentary successions: An example from the Janggi Basin, south‐eastern part of the Korean Peninsula
Authors: Gihm Yong Sik , Kim Min‐Cheol , Chae Yong‐Un , Hwang In Gul , Son Moon 
Published: April 2022

AbstractIn extensional and transtensional basins, the dual action of basin‐forming tectonism and explosive volcanic activity results in deposition of complex volcano‐sedimentary successions. Since both aspects contemporaneously affect sediment‐dispersal systems, it is difficult to distinguish one from the other by analyzing volcano‐sedimentary successions. To discriminate tectonic influence, basin fills of the Miocene, pull‐apart Janggi Basin were investigated. Here, the contemporaneous influence of tectonic subsidence and explosive volcanism formed <966 m thick, conformable volcano‐sedimentary successions composed of laterally extensive, pumice‐bearing, unwelded pyroclastic deposits and nonmarine sedimentary rocks formed under humid climatic conditions. Based on Laser Ablation – Multiple Collector – Inductively Coupled Plasma Mass Spectrometry zircon U–Pb age data, these successions were deposited from 21.1 ± 0.2 to 20.1 ± 0.1 Ma. After deposition of basinwide, tens of metres thick, and unwelded pyroclastic deposits, the directly overlying facies successions (FS‐1 and FS‐2) show contrasting depositional features to the classical model of volcaniclastic sedimentation. Facies succession‐1 is represented by fluvial conglomerates composed mostly of (sub)rounded pebble and cobble sourced from basement. The supply of basement‐derived clasts through fluvial systems resulted from development of physiographic relief during or soon after the eruption by syndepositional tectonic subsidence. Facies succession‐2 occurs directly on pyroclastic deposits that cover FS‐1 and show coarsening‐upward trends, and is composed of basal lacustrine mudstones and overlying resedimented volcaniclastic sandstones showing a progradational geometry, interpreted as a result of progressive filling of the lake by remobilized volcaniclastic sediments. Occurrence of basal lacustrine laminated mudstones indicates that syndepositional creation of the accommodation by tectonic subsidence exceeded forceful input of pyroclastic and remobilized volcaniclastic sediments, resulting in a delayed sedimentary response to explosive volcanic eruptions. This study shows that, despite voluminous production of volcaniclastic sediments, tectonic activity controlled sediment type and stacking patterns. Therefore, these depositional features allow to discriminate tectonic effects from complex volcano‐sedimentary successions, enabling to reconstruct basin evolution.
Association between alexithymia and substance use: A systematic review and meta‐analysis
Authors: Honkalampi Kirsi , Jokela Markus , Lehto Soili M. , Kivimäki Mika , Virtanen Marianna 
Published: April 2022

Alexithymia has been associated with substance use, but the magnitude of the association has not been evaluated and sub‐group differences, if any, are unknown. The aim of this meta‐analysis is to systematically review the association between alexithymia and substance use (alcohol or illicit drugs). We identified studies through a systematic review of PubMed and Web of Science and obtained a total of 52 publications using the Toronto Alexithymia Scale‐20 scale. Random effects meta‐analysis was used to evaluate the overall and sub‐group associations. Of the studies, 50 were cross‐sectional and two longitudinal. Alexithymia was associated with any substance use (Cohen’s d = 0.62, 95% confidence interval [CI] 0.49–0.76), with little difference between estimates for use of alcohol or illicit drugs. A stronger association was observed for the alexithymia dimension “Difficulty in Identifying Feelings” (d = 0.64, 95% CI = 0.47–0.81) and “Difficulty in Describing Feelings” (d = 0.44, 95% CI = 0.32–0.55) than for “Externally Oriented Thinking” (d = 0.19, 95% CI = 0.09–0.28). The association was stronger in studies with clinical patient populations (d = 0.83, 95% CI = 0.62–1.05) than in those investigating general or student populations, and in studies with a majority of male rather than female participants. These findings suggest a strong overall association between alexithymia and substance use and a very strong association among clinical patient populations. The association may be stronger with the emotion‐related dimensions than with the cognition‐related dimension of alexithymia. As nearly all the studies were cross‐sectional, more longitudinal studies are needed.
Investigating preservice teachers' assessment skills: Relating aspects of teacher noticing and content knowledge for assessing student thinking in written work
Authors: Namakshi Nama , Warshauer Hiroko K. , Strickland Sharon , McMahon Lauren 
Published: April 2022

AbstractThis mixed methods study explored the development of elementary and middle school preservice teachers' (PSTs) learning to assess student thinking through analysis of students' written work. Six sections of the first mathematics content course for teaching implemented two writing assignments focused on analysis of student work aligned to the mathematics topics covered in the PSTs' classes. Using quantitative methodology, we examined the PSTs' (n = 99) change in their noticing and assessment skills of attending to and interpreting students' thinking. We also documented their mathematical content knowledge (MKT) as measured by the Learning for Mathematics Teaching in the domains of specialized content knowledge and knowledge of content and students. Findings show that the PSTs increased in their assessment skills and in their MKT. Using a qualitative methodology on interview data of a subset of eight PSTs, we found they acknowledged that having a firm grasp of mathematical content is essential to understanding and explaining student thinking. Findings indicate that engaging PSTs in the real work of teaching such as noticing and assessing students' thinking through written work at the early stages of their teacher preparation may motivate PSTs to learn mathematics more deeply with an eye towards strengthening their assessment skills.