bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome sequencing of 320 Chinese children with epilepsy: a clinical and molecular study
Authors: Zou Dongfang , Wang Lin , Liao Jianxiang , Xiao Hongdou , Duan Jing , Zhang Tongda , Li Jianbiao , Yin Zhenzhen , Zhou Jing , Yan Haisheng , Huang Yushan , Zhan Nianji , Yang Ying , Ye Jingyu , Chen Fang , Zhu Shida , Wen Feiqiu , Guo Jian 
Published: June 2021

Abstract
The aim of this study is to evaluate the diagnostic value of genome sequencing in children with epilepsy, and to provide genome sequencing-based insights into the molecular genetic mechanisms of epilepsy to help establish accurate diagnoses, design appropriate treatments and assist in genetic counselling.
We performed genome sequencing on 320 Chinese children with epilepsy, and interpreted single-nucleotide variants and copy number variants of all samples. The complete pedigree and clinical data of the probands were established and followed up. The clinical phenotypes, treatments, prognoses and genotypes of the patients were analysed.
Age at seizure onset ranged from 1 day to 17 years, with a median of 4.3 years. Pathogenic/likely pathogenic variants were found in 117 of the 320 children (36.6%), of whom 93 (29.1%) had single-nucleotide variants, 22 (6.9%) had copy number variants and two had both single-nucleotide variants and copy number variants. Single-nucleotide variants were most frequently found in SCN1A (10/95, 10.5%), which is associated with Dravet syndrome, followed by PRRT2 (8/95, 8.4%), which is associated with benign familial infantile epilepsy, and TSC2 (7/95, 7.4%), which is associated with tuberous sclerosis. Among the copy number variants, there were three with a length &lt;25 kilobases. The most common recurrent copy number variants were 17p13.3 deletions (5/24, 20.8%), 16p11.2 deletions (4/24, 16.7%), and 7q11.23 duplications (2/24, 8.3%), which are associated with epilepsy, developmental retardation and congenital abnormalities. Four particular 16p11.2 deletions and two 15q11.2 deletions were considered to be susceptibility factors contributing to neurodevelopmental disorders associated with epilepsy.
The diagnostic yield was 75.0% in patients with seizure onset during the first postnatal month, and gradually decreased in patients with seizure onset at a later age. Forty-two patients (13.1%) were found to be specifically treatable for the underlying genetic cause identified by genome sequencing. Three of them received corresponding targeted therapies and demonstrated favourable prognoses.
Genome sequencing provides complete genetic diagnosis, thus enabling individualized treatment and genetic counselling for the parents of the patients. Genome sequencing is expected to become the first choice of methods for genetic testing of patients with epilepsy.
Downregulation of HERC5 E3 ligase attenuates the ubiquitination of CtBP1 to inhibit apoptosis in colorectal cancer cells
Authors: Zhu Lin , Wu Jing , Liu Hong 
Published: June 2021

Abstract
The homologous to E6AP C-terminus (HECT) domain and RCC1-like domain-containing (HERC) proteins can function as tumour suppressors and as oncogenes, depending on the cancer type. However, the expression patterns of HERCs in colorectal cancer (CRC) cells are unclear. Here, we show that only HERC1 and HERC5 are downregulated in CRC tumours, and we focus our study on revealing HERC5-mediating signalling because the change in downregulation is much more obvious for HERC5 than for HERC1. We demonstrate that HERC5 recruits an adaptor protein, CREB-binding protein, to ubiquitinate C-terminal binding protein 1 (CtBP1) in non-cancerous colon cells. The downregulation of HERC5 in CRC cells attenuates the ubiquitination of CtBP1, which then accumulates and assembles into a transcriptional complex with histone deacetylase 1 and a transcription factor c-MYC. This transcriptional complex binds to the promoters of three proapoptotic genes, Bcl2 associated X (BAX), Bcl2 interacting killer (BIK) and p53upregulated modulator of apoptosis (PUMA), and inhibits their expression, thereby suppressing apoptotic signalling and promoting tumourigenesis. Overexpression of HERC5, downregulation of CtBP1 or blocking of the CtBP1 function with its inhibitors (NSC95397 and 4-methylthio-2-oxobutyric acid [MTOB]) significantly prevents CRC cell proliferation in vitro and tumour growth in vivo. Combining NSC95397 (or MTOB) with chemotherapeutic drugs (oxaliplatin or capecitabine) gives a much stronger inhibition of cell proliferation and tumour growth compared with their single treatments. Collectively, our results reveal that downregulation of HERC5 E3 ligase attenuates the ubiquitination of CtBP1 to inhibit apoptosis. Therefore, CtBP1 may be a promising target in CRC chemotherapy.
The Burden of Respiratory Syncytial Virus in Children Under 2 Years of Age in a Rural Community in Maharashtra, India
Authors: Satav Ashish , Crow Rowena , Potdar Varsha , Dani Vibhawari , Satav Shilpa , Chadha Mandeep , Hessong Danielle , Carosone-Link Phyllis , Palaskar Sameer , Simões Eric A F 
Published: June 2021

Abstract

Background
Globally, respiratory syncytial virus (RSV) is a common cause of acute lower tract infection (LRTI) in children younger than 2 years of age, but there are scant population-based studies on the burden of RSV illness in rural communities and no community studies in preterm infants.

Methods
Active surveillance of LRTI was performed in the community and hospital setting for the population of 93 tribal villages in Melghat, Central India, over 4 respiratory seasons. A nasopharyngeal swab was obtained from cases presenting as a severe LRTI for molecular analysis of respiratory pathogens including RSVA and B.

Results
High rates of RSV-associated LRTI were found in preterm and term infants beyond 6 months of age, extending into the second year of life. Community severe RSV LRTI rates for 0–11 months of age was 22.4 (18.6–27.0)/1000 child-years (CY) and the hospital-associated rate was 14.1 (11.1–17.8)/1000 CY. For preterm infants, these rates were 26.2 (17.8–38.5)/1000 CY and 12.6 (7.2–22.0)/1000 CY. Comparable rates in the first 6 months were 15.9 (11.8–21.4)/1000 CY and 12.9 (9.3–18.0)/1000 CY in term infants and 26.3 (15.4–45.0)/1000 CY and 10.1 (4.2–24.2)/1000 CY for preterms. The single RSV B season had higher incidences of RSV LRTI in every age group than the 2 RSV A seasons in both preterm and term infants. There were 11 deaths, all term infants.

Conclusions
Studies restricted to the healthcare settings significantly underestimate the burden of RSV LRTI and preterm and term infants have comparable burdens of disease in this rural community.
Locating highly connected clusters in large networks with HyperLogLog counters
Authors: Weedage Lotte , Litvak Nelly , Stegehuis Clara 
Published: June 2021

Abstract
In this article, we introduce a new method to locate highly connected clusters in a network. Our proposed approach adapts the HyperBall algorithm to localize regions with a high density of small subgraph patterns in large graphs in a memory-efficient manner. We use this method to evaluate three measures of subgraph connectivity: conductance, the number of triangles and transitivity. We demonstrate that our algorithm, applied to these measures, helps to identify clustered regions in graphs and provides good seed sets for community detection algorithms such as PageRank-Nibble. We analytically obtain the performance guarantees of our new algorithms and demonstrate their effectiveness in a series of numerical experiments on synthetic and real-world networks.
A spinach genome assembly with remarkable completeness, and its use for rapid identification of candidate genes for agronomic traits
Authors: Hirakawa Hideki , Toyoda Atsushi , Itoh Takehiko , Suzuki Yutaka , Nagano Atsushi J , Sugiyama Suguru , Onodera Yasuyuki 
Published: June 2021

Abstract
Spinach (Spinacia oleracea) is grown as a nutritious leafy vegetable worldwide. To accelerate spinach breeding efficiency, a high-quality reference genome sequence with great completeness and continuity is needed as a basic infrastructure. Here, we used long-read and linked-read technologies to construct a de novo spinach genome assembly, designated SOL_r1.1, which was comprised of 287 scaffolds (total size: 935.7 Mb; N50 = 11.3 Mb) with a low proportion of undetermined nucleotides (Ns = 0.34%) and with high gene completeness (BUSCO complete 96.9%). A genome-wide survey of resistance gene analogues identified 695 genes encoding nucleotide-binding site domains, receptor-like protein kinases, receptor-like proteins and transmembrane-coiled coil domains. Based on a high-density double-digest restriction-site associated DNA sequencing-based linkage map, the genome assembly was anchored to six pseudomolecules representing ∼73.5% of the whole genome assembly. In addition, we used SOL_r1.1 to identify quantitative trait loci for bolting timing and fruit/seed shape, which harbour biologically plausible candidate genes, such as homologues of the FLOWERING LOCUS T and EPIDERMAL PATTERNING FACTOR-LIKE genes. The new genome assembly, SOL_r1.1, will serve as a useful resource for identifying loci associated with important agronomic traits and for developing molecular markers for spinach breeding/selection programs.
Learner-initiated exploratory practice: revisiting curiosity
Authors: Kato Yoshitaka , Hanks Judith 
Published: June 2021

Abstract
This paper investigates the potential of learner-initiated exploratory practice (EP), which encourages learners to set their own investigative agenda based on their curiosity-driven puzzles. A case study was conducted in a remedial course for undergraduate students at a university in Japan. Data included student puzzles, posters, and reflective questionnaires. Student investigations of their puzzles remind teachers and researchers of the affordances of learning from learners. The results suggested that, despite their previously disoriented attitudes towards learning English, this form of fully inclusive practitioner research, EP, provides learners with an opportunity to realize their curiosity and reinvigorate their motivation towards language learning.
Homeloss: Narratives of Eviction in Contemporary Spain
Authors: Usoz de la Fuente Maite 
Published: June 2021

Abstract
This article considers how the prospect of losing one’s home to eviction is portrayed in three contemporary Spanish literary texts: Cristina Fallarás’s A la puta calle. Crónica de un desahucio (2013), Doménico Chiappe’s Tiempo de encierro (2013), and Isaac Rosa and Cristina Bueno’s Aquí vivió. Historia de un desahucio (2016). All three texts feature middle-class households at risk of homelessness due to the effects of the 2008 financial crisis, thus testifying to the suffering of hundreds of thousands of Spaniards in the wake of the global recession. Yet as this article argues, these narratives transcend the purely testimonial, as they problematize the very act of storytelling and thus draw our attention to the ways in which narrative – in its broadest sense – can be used to construct, justify or contest the socio-historical context we inhabit.
Zoledronate Extends Health Span and Survival via the Mevalonate Pathway in a FOXO-dependent Manner
Authors: Chen Zhengqi , Cordero Julia , Alqarni Adel M , Slack Cathy , Zeidler Martin P , Bellantuono Ilaria 
Published: June 2021

Abstract
Over recent decades, increased longevity has not been paralleled by extended health span, resulting in more years spent with multiple diseases in older age. As such, interventions to improve health span are urgently required. Zoledronate (Zol) is a nitrogen-containing bisphosphonate, which inhibits the farnesyl pyrophosphate synthase enzyme, central to the mevalonate pathway. It is already used clinically to prevent fractures in osteoporotic patients, who have been reported to derive unexpected and unexplained survival benefits. Using Drosophila as a model we determined the effects of Zol on life span, parameters of health span (climbing ability and intestinal dysplasia), and the ability to confer resistance to oxidative stress using a combination of genetically manipulated Drosophila strains and Western blotting. Our study shows that Zol extended life span, improved climbing activity, and reduced intestinal epithelial dysplasia and permeability with age. Mechanistic studies showed that Zol conferred resistance to oxidative stress and reduced accumulation of X-ray-induced DNA damage via inhibition of farnesyl pyrophosphate synthase. Moreover, Zol was associated with inhibition of phosphorylated AKT in the mammalian traget of rapamycin pathway downstream of the mevalonate pathway and required dFOXO for its action, both molecules associated with increased longevity. Taken together, our work indicates that Zol, a drug already widely used to prevent osteoporosis and dosed only once a year, modulates important mechanisms of aging. Its repurposing holds great promise as a treatment to improve health span.
Utilizing Principles of Life-Span Developmental Psychology to Study the Complexities of Resilience Across the Adult Life Span
Authors: Infurna Frank J 
Published: June 2021

AbstractLife-span developmental psychology includes a broad array of principles that have wide application to studying adult development and aging. Three principles have guided my past, current, and future research: (a) development being a cumulative, lifelong process with no one period taking precedence; (b) multiple processes influence development (e.g., age-, pathology-, nonnormative, and mortality-related processes); and (c) development is multidirectional and multidimensional. This paper elaborates on how these principles have guided my research studying resilience to adversity across the adult life span and how my research aligns with guiding elements of resilience across definitions and literatures. I also discuss my current and future research of applying these principles to studying resilience in midlife, which emphasizes how the defining features of midlife lend themselves to examining resilience, midlife continues to not be well understood, midlife health foreshadows health in old age, and the experience of midlife will evolve in the context of an increasingly diverse society. The last section elaborates on additional directions for future research, such as the promise of intensive longitudinal research designs that incorporate qualitative approaches and examining historical changes in midlife health and well-being. In conclusion, a life-span developmental psychology framework has wide application for elucidating the nature of resilience across the adult life span through the integration of its principles with existing paradigms and research designs that blend contemporary methods with mixed methodology.
Pertussis Toxin Promotes Pulmonary Hypertension in an Infant Mouse Model of Bordetella pertussis Infection
Authors: Scanlon Karen M , Chen Ling , Carbonetti Nicholas H 
Published: June 2021

Abstract
Pertussis, caused by Bordetella pertussis, is a reemerging disease that can produce severe disease manifestations in infants, including pulmonary hypertension (PH). B. pertussis-induced PH is a major risk factor for infection-induced death, but the molecular mechanisms promoting PH are unknown and there is no effective treatment. We examined B. pertussis-induced PH in infant and adult mouse models of pertussis by Fulton index, right heart catheterization, or Doppler echocardiogram. Our results demonstrate that B. pertussis-induced PH is age related and dependent on the expression of pertussis toxin by the bacterium. Hence, pertussis toxin-targeting treatments may ameliorate PH and fatal infant infection.
Nonsurvival Distributions in Pediatric Burn Patients: A Comparative Study of Two National Databases
Authors: Wermine Kendall , Gotewal Sunny , Schober Marc A , Africa Robert E , Hallman Taylor , Cuartas-Olarte Andres , Ko Andrew , Torres Mark Jordan M , Peterson Joshua M , Golovko Georgiy , Song Juquan , El Ayadi Amina , Wolf Steven E 
Published: June 2021

Abstract
A contemporary, age-specific model for the distribution of burn mortality in children has not been developed for over a decade. Using data from TriNetX, a global federated health research network, and the American Burn Association’s Nation Burn Repository (NBR), we investigated nonsurvival distributions for pediatric burns in the United States. Pediatric burn patients aged 0 to 20 between 2010 and 2020 were identified in TriNetX from 41 Healthcare Organizations using ICD-10 codes (T.20-T.30) and identified as lived/died. These were compared to the nonsurvival data from 90 certified burn centers in the NBR database between 2016 and 2018. The patient population was stratified by age into subgroups of 0 to 4, 5 to 9, 10 to 14, and 15 to 20 years. Overall, mortality rates for pediatric burn patients were found to be 0.62% in NBR and 0.52% in TrinetX. Boys had a higher incidence of mortality than girls in both databases (0.34% vs 0.28% NBR, P = .13; 0.31% vs 0.21% TriNetX, P &lt; .001). Comparison of ethnic cohorts between 2010 to 2015 and 2016 to 2020 subgroups showed that nonsurvival rates of African American children increased relative to white children (TriNetX, P &lt; .001); however, evidence was insufficient to conclude that African American children die more frequently than other ethnicities (NBR, P = .054). When analyzing subgroups in TriNetX, burned children aged 5 to 9 had significantly increased frequency of nonsurvival (P &lt; .001). However, NBR data suggested that children aged 0 to 4 experience the highest frequency of mortality (P &lt; .001). The nonsurvival distributions between these two large databases accurately reflect nonsurvival rates in burned children.
Parasitoid Communities in the Variable Agricultural Environments of Blueberry Production in the Southeastern United States
Authors: Schmidt Jason M , Whitehouse Tyler S , Neupane Subin , Miranda Rezende Sarah , Sial Ashfaq , Gariepy Tara D 
Published: June 2021

Abstract
In blueberry crops, there are multiple pest species, and some of those can be suppressed by natural enemies including parasitoid wasps and predators. Parasitoid wasps occur within the environment often tracking pest species for food resources to complete their lifecycle. These small wasps are also sensitive to agricultural environments including agrichemicals, habitat availability, and climate. We investigated how the structure of parasitoid communities varied between organic and conventional blueberry systems, and how the communities of these parasitoids varied within field spatial scales (forested border vs edge vs interior). With the lower intensity of agricultural interventions occurring in organic systems and forested borders, we predicted more stable parasitoid numbers that would be insulated from predicted climate variability. In our study, parasitoids were observed in low abundance in each cropping system, with community structure dependent on both management practice and field position. Unmanaged blueberry fields and forested field borders contained more parasitoid families, and in conventional systems, we saw fewer families present in the field interior as compared to field borders. In this first study to characterize Southern parasitoid communities in blueberry production systems, we observed over 50 genera of parasitoids, with a few dominant families (Braconidae and Ichneumonidae) that would contribute to biological control in blueberry systems. Overall, we captured few parasitoids, which indicates a potential vulnerability in biological control, and the need for further research using other sampling techniques to better understand these parasitoid communities.
Intra-abdominal rectal perforation post-haemorrhoidal artery ligation operation and converted Ligasure open haemorrhoidectomy
Authors: Simon Natalie , Saiyara Noshin , Kim Hyun-Kyung , Gercek Yuksel 
Published: June 2021

Abstract
We report an unfortunate case of rectal perforation and subsequent peritonitis in a 74-year-old lady who underwent haemorrhoidal artery ligation in order to treat complex large external and internal haemorrhoids. Serious complications following haemorrhoid surgery are rare and this is the first documented case of delayed intra-abdominal rectal perforation following a haemorrhoid artery ligation operation and converted Ligasure open haemorrhoidectomy.
In-flight medical emergencies during commercial travel
Authors: Ceyhan Mehmet Ali , Menekşe İbrahim Ethem 
Published: June 2021

AbstractBackgroundGrowing number of passengers travelling by air is associated with increased in-flight emergency medical events (IEMEs). However, there are scarce data regarding IEMEs during commercial travels. In this study, analysis of IEMEs occurring among adult and paediatric passengers during commercial international and domestic flights of a major airline company was targeted.MethodsData regarding IEMEs recorded in all international and domestic flights of a major airline company between 1 January 2018 and 31 December 2020 were collected. Demographics, adult and paediatric IEMEs, in-flight deaths and aircraft diversions (ADs) were analysed.ResultsTotal number of passengers was 177 400 748 and a number of 22 541 (0.012%) IEMEs occurred. The frequency of IEMEs per 1 million passengers was 127. The number of male patients suffering from IEMEs was 8387 (37.2%), while the number female patients was 10 853 (48.1%). Median age of adult and paediatric patients were 43, [32–57], 4, [2–10], respectively. The most common cause of IEMEs in adult patients was headache (3424 IEMEs, 15.1%) and it was fever in paediatric patients (688 IEMEs, 3.05%). Multiple symptoms were present in 8449 IEMEs (37.4%). On-board doctors managed events in more than half of IEMEs (13 295 IEMEs, 58.9%). AD was required in 255 (1.13%) IEMEs. The most common reason for AD was chest pain (45 IEMEs, 17.6%) in adult patients. The most common reason for AD in paediatric patients was epileptic seizures (nine IEMEs, 3.5%). A total of 46 (0.2%) patients, including 2 (0.008%) paediatric patients, died.ConclusionsMajority of IEMEs are not life-threatening conditions, which can be easily managed by cabin crew or on-board doctors without AD. Multiple symptoms can be present in a patient suffering from IEME. Ground-to-air medical assistance may help optimization of diagnosis and decision for AD.