bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxic tumour cell-derived exosomal miR-340-5p promotes radioresistance of oesophageal squamous cell carcinoma via KLF10
Authors: Chen Fangyu , Xu Bing , Li Jie , Yang Xi , Gu Junjie , Yao Xijuan , Sun Xinchen 
Published: January 2021

Abstract
Background
Radiotherapy resistance is a major obstacle in the treatment of oesophageal squamous cell carcinoma (OSCC). Hypoxia is a critical cause of radioresistance. However, the communication between hypoxic cells and aerobic cells via exosomes during the transfer of radiation resistance remains unclear.

Methods
Exo-miR-340-5p levels were analysed by RNA-seq and qRT-PCR. We co-cultured OSCC cells with isolated normoxic and hypoxic exosomes to study their impact on radiosensitivity. We used a specific exo-miR-340-5p mimic and knock-down retrovirus to explore the role of this miRNA in the transfer of radioresistance from hypoxic to normoxic cells. Dual-luciferase reporter and RIP assays were used to verify KLF10 as a putative target of miR-340-5p. Several in vitro assays were conducted and xenograft models were established to investigate the effect of exo-miR-340-5p on OSCC radiosensitivity. The plasma exo-miR-340-5p levels in OSCC patients were analysed to study the clinical value of this parameter.

Results
Hypoxic exosomes alleviated radiation-induced apoptosis and accelerated DNA damage repair. miR-340-5p was highly expressed in hypoxic exosomes and was transferred into normoxic cells, where it induced radioresistance. Overexpression of miR-340-5p in normoxic OSCC cells mimicked the radioresistance of cells co-cultured with hypoxic exosomes. Knockdown of miR-340-5p in hypoxic exosomes reversed the radioresistance effect, indicating that exo-miR-340-5p is critical for hypoxic EV-transferred radioresistance. KLF10 was identified as the direct target of miR-340-5p. Moreover, metformin was found to increase the expression of KLF10 and enhance the radiosensitivity of OSCC. Higher levels of miR-340-5p in the plasma exosomes from OSCC patients are related to a poorer radiotherapy response and prognosis.

Conclusions
Hypoxic tumour cell-derived exosomal miR-340-5p confers radioresistance in OSCC by targeting KLF10/UVRAG, suggesting that miR-340-5p could be a potential biomarker and therapeutic target for the enhancement of radiosensitivity in OSCC. Metformin can increase KLF10 expression, which ameliorates the radioresistance induced by exo-miR-340-5p transfer. Therefore, metformin could be further investigated as a therapeutic option for the treatment of OSCC.
A validity study of the rapid emergency Triage and treatment system for children
Authors: Ødegård Siv Steinsmo , Tran Thuy , Næss-Pleym Lars E. , Risnes Kari , Døllner Henrik 
Published: January 2021

Abstract
Background
The Scandinavian Rapid Emergency Triage and Treatment System-pediatric (RETTS-p) is a reliable triage system that includes both assessment of vital parameters and a systematic approach to history and symptoms. In Scandinavia, the system is used in most pediatric emergency departments (PED). We aimed to study the validity of RETTS-p.

Methods
We conducted a study based on triage priority ratings from all children assessed in 2013 and 2014 to the PED at St. Olavs University Hospital Trondheim, Norway. Patients were assigned one of four priority ratings, based on the RETTS-p systematic evaluation of individual disease manifestations and vital parameter measurements. In the absence of a gold-standard for true disease severity, we assessed whether priority ratings were associated with 3 proxy variables: 1) hospitalization to the wards (yes vs. no), 2) length of hospital stay (≤ mean vs. > mean, and 3) referral to pediatric intensive care (yes vs. no). We further compared priority ratings with selected diagnoses and procedure codes at discharge.

Results
Six thousand three hundred sixty-eight children were included in the study. All analyses were performed in the entire population and separately in pediatric sub-disciplines, medicine (n = 4741) and surgery (general and neurosurgery) (n = 1306). In the entire population and the sub-disciplines, a high priority rate was significantly associated with hospitalization to wards, a longer hospital stay and referral to the pediatric intensive care unit compared to patients with low priority. We observed a dose-response relationship between increased triage code level and indicators of more severe disease (p-trend < 0.001). For the same three proxy variables, the sensitivity was 54, 61 and 83%, respectively, and the specificity 66, 62 and 57%, respectively. Subgroup analyzes within the most common complaints, demonstrated that more severe conditions were higher prioritized than less severe conditions for both medical and surgical patients. Overall, children with surgical diagnoses attained lower priority ratings than children with medical diagnoses.

Conclusions
RETTS-p priority ratings varies among a broad spectrum of pediatric conditions and mirror medical urgency in both medical and surgical disciplines. RETTS-p is a valid triage system for children as used in a university hospital setting.
Transposable element subfamily annotation has a reproducibility problem
Authors: Carey Kaitlin M. , Patterson Gilia , Wheeler Travis J. 
Published: January 2021

AbstractBackgroundTransposable element (TE) sequences are classified into families based on the reconstructed history of replication, and into subfamilies based on more fine-grained features that are often intended to capture family history. We evaluate the reliability of annotation with common subfamilies by assessing the extent to which subfamily annotation is reproducible in replicate copies created by segmental duplications in the human genome, and in homologous copies shared by human and chimpanzee.ResultsWe find that standard methods annotate over 10% of replicates as belonging to different subfamilies, despite the fact that they are expected to be annotated as belonging to the same subfamily. Point mutations and homologous recombination appear to be responsible for some of this discordant annotation (particularly in the young Alu family), but are unlikely to fully explain the annotation unreliability.ConclusionsThe surprisingly high level of disagreement in subfamily annotation of homologous sequences highlights a need for further research into definition of TE subfamilies, methods for representing subfamily annotation confidence of TE instances, and approaches to better utilizing such nuanced annotation data in downstream analysis.
Retroactive interference model of forgetting
Authors: Georgiou Antonios , Katkov Mikhail , Tsodyks Misha 
Published: January 2021

AbstractMemory and forgetting constitute two sides of the same coin, and although the first has been extensively investigated, the latter is often overlooked. A possible approach to better understand forgetting is to develop phenomenological models that implement its putative mechanisms in the most elementary way possible, and then experimentally test the theoretical predictions of these models. One such mechanism proposed in previous studies is retrograde interference, stating that a memory can be erased due to subsequently acquired memories. In the current contribution, we hypothesize that retrograde erasure is controlled by the relevant “importance” measures such that more important memories eliminate less important ones acquired earlier. We show that some versions of the resulting mathematical model are broadly compatible with the previously reported power-law forgetting time course and match well the results of our recognition experiments with long, randomly assembled streams of words.
The National Immunization Technical Advisory Group in Israel
Authors: Stein-Zamir Chen , Rishpon Shmuel 
Published: January 2021

AbstractNational Immunization Technical Advisory Groups (NITAGs) are defined by the World Health Organization as multidisciplinary groups of health experts who are involved in the development of a national immunization policy. The NITAG has the responsibility to provide independent, evidence-informed advice to the policy makers and national programme managers, on policy issues and questions related to immunization and vaccines.This paper aims to describe the NITAG in Israel. The Israeli NITAG was established by the Ministry of Health in1974. The NITAG’s full formal name is “the Advisory Committee on Infectious Diseases and Immunizations in Israel”. The NITAG is charged with prioritizing choices while granting maximal significance to the national public health considerations. Since 2007, the full minutes of the NITAG’s meetings have been publicly available on the committee’s website (at the Ministry of Health website, in Hebrew).According to the National Health Insurance Law, all residents of Israel are entitled to receive universal health coverage. The health services basket includes routine childhood immunizations, as well as several adult and post - exposure vaccinations. The main challenge currently facing the NITAG is establishing a process for introducing new vaccines and updating the vaccination schedule through the annual update of the national health basket. In the context of the annual update, vaccines have to “compete” with multiple medications and technologies which are presented to the basket committee for inclusion in the national health basket. Over the years, the Israeli NITAG’s recommendations have proved essential for vaccine introduction and scheduling and for communicable diseases control on a national level. The NITAG has established structured and transparent working processes and a decision framework according to WHO standards, which is evidence-based and country-specific to Israel.The recent global COVID-19 pandemic is a major concern for all countries as well as a challenge for NITAGs. Currently, the NITAGs have a key role in advising both on sustainment of the routine immunization programs and on planning of the COVID-19 vaccination campaigns, with ongoing updates and collaboration with the Ministry of Health and health organizations.
On continuity of the fractional derivative of the time-fractional semilinear pseudo-parabolic systems
Authors: Karapinar Erdal , Binh Ho Duy , Luc Nguyen Hoang , Can Nguyen Huu 
Published: January 2021

AbstractIn this work, we study an initial value problem for a system of nonlinear parabolic pseudo equations with Caputo fractional derivative. Here, we discuss the continuity which is related to a fractional order derivative. To overcome some of the difficulties of this problem, we need to evaluate the relevant quantities of the Mittag-Leffler function by constants independent of the derivative order. Moreover, we present an example to illustrate the theory.
Diterpenoids as potential anti-malarial compounds from Andrographis paniculata
Authors: Dwivedi Manish Kumar , Mishra Shringika , Sonter Shruti , Singh Prashant Kumar 
Published: January 2021

AbstractBackgroundThe objectives of the current study are to evaluate the traditionally used medicinal plantsAndrographis paniculatafor in vitro anti-malarial activity against human malarial parasitePlasmodium falciparumand to further characterize the anti-malarial active extract ofA. paniculatausing spectroscopic and chromatographic methods.ResultsThe chloroform extract ofA. paniculatadisplayed anti-malarial activity with IC50values 6.36 μg/ml against 3D7 strain and 5.24 μg/ml against K1 strains respectively with no evidence of significant cytotoxicity against mammalian cell line (CC50> 100 μg/ml). LC-MS analysis of the extract led to the identification of 59 compounds based on their chromatographic and mass spectrometric features (a total of 35 compounds are present in positive ion and 24 compounds in negative ion mode). We have identified 5 flavonoids and 30 compounds as diterpenoids in positive ion mode, while in the negative mode all identified compounds were diterpenoids. Characterization of the most promising class of compound diterpenoids using HPLC-LC-ESI-MS/MS was also undertaken.ConclusionsThe in vitro results undoubtedly validate the traditional use ofA. paniculatafor the treatment of malaria. The results have led to the identification of diterpenoids from IGNTU_06 extract as potential anti-malarial compounds that need to be further purified and analyzed in anti-malarial drug development programs.Graphical abstract
Isolation and optimized production of putative antimicrobial compounds from Egyptian soil isolate Streptomyces sp. MS. 10
Authors: Sebak Mohamed , Saafan Amal E. , Abdelghani Sameh , Bakeer Walid , Moawad Abeer S. , El-Gendy Ahmed O. 
Published: January 2021

Abstract
Background
The rapid spread of antibiotic resistance has increased research interest in the discovery of natural products, mainly from actinomycetes, which have been the primary source of antimicrobial compounds. This study aimed to isolate, characterize, and optimize the production of some of the bioactive compounds from bioactive soil actinomycetes.

Results
One promising soil actinomycete, which was molecularly identified as Streptomyces sp. and designated as Streptomyces sp. MS. 10, showed broad-spectrum antimicrobial activity, including activity against methicillin-resistant Staphylococcus aureus. Thus, it was selected for isolation of its major bioactive compounds. Polymerase chain reaction amplification of the genes responsible for antibiotic biosynthesis showed the presence of genes encoding type I and type II polyketide synthase. Liquid chromatography-mass spectrometry analysis found that the major antimicrobial compounds produced by Streptomyces sp. MS. 10 were weakly ionized bioactive secondary metabolites. A large-scale fermentation experiment of Streptomyces sp. MS. 10 using pre-optimized culture conditions followed by bioassay-guided chromatographic separation of its secondary metabolites resulted in the isolation of putative bioactive compounds that were identified as fatty acids using proton nuclear magnetic resonance spectroscopy.

Conclusions
Egyptian soil is still a good source for exploring bioactive actinomycetes. Additionally, this study highlighted the importance of combining both physicochemical and genotypic characterization with spectroscopic analysis of the major natural products when isolating bioactive metabolites.
Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer: ASCO Guideline Update
Authors: Virgo Katherine S. , Rumble R. Bryan , de Wit Ronald , Mendelson David S. , Smith Thomas J. , Taplin Mary-Ellen , Wade James L. , Bennett Charles L. , Scher Howard I. , Nguyen Paul L. , Gleave Martin , Morgan Scott C. , Loblaw Andrew , Sachdev Sean , Graham David L. , Vapiwala Neha , Sion Amy M. , Simons Virgil H. , Talcott James 
Published: January 2021

PURPOSE Update all preceding ASCO guidelines on initial hormonal management of noncastrate advanced, recurrent, or metastatic prostate cancer. METHODS The Expert Panel based recommendations on a systematic literature review. Recommendations were approved by the Expert Panel and the ASCO Clinical Practice Guidelines Committee. RESULTS Four clinical practice guidelines, one clinical practice guidelines endorsement, 19 systematic reviews with or without meta-analyses, 47 phase III randomized controlled trials, nine cohort studies, and two review papers informed the guideline update. RECOMMENDATIONS Docetaxel, abiraterone, enzalutamide, or apalutamide, each when administered with androgen deprivation therapy (ADT), represent four separate standards of care for noncastrate metastatic prostate cancer. Currently, the use of any of these agents in any particular combination or series cannot be recommended. ADT plus docetaxel, abiraterone, enzalutamide, or apalutamide should be offered to men with metastatic noncastrate prostate cancer, including those who received prior therapies, but have not yet progressed. The combination of ADT plus abiraterone and prednisolone should be considered for men with noncastrate locally advanced nonmetastatic prostate cancer who have undergone radiotherapy, rather than castration monotherapy. Immediate ADT may be offered to men who initially present with noncastrate locally advanced nonmetastatic disease who have not undergone previous local treatment and are unwilling or unable to undergo radiotherapy. Intermittent ADT may be offered to men with high-risk biochemically recurrent nonmetastatic prostate cancer. Active surveillance may be offered to men with low-risk biochemically recurrent nonmetastatic prostate cancer. The panel does not support use of either micronized abiraterone acetate or the 250 mg dose of abiraterone with a low-fat breakfast in the noncastrate setting at this time. Additional information is available at www.asco.org/genitourinary-cancer-guidelines .
Epigenome-Wide Association Study of Thyroid Function Traits Identifies Novel Associations of fT3 With KLF9 and DOT1L
Authors: Lafontaine Nicole , Campbell Purdey J , Castillo-Fernandez Juan E , Mullin Shelby , Lim Ee Mun , Kendrew Phillip , Lewer Michelle , Brown Suzanne J , Huang Rae-Chi , Melton Phillip E , Mori Trevor A , Beilin Lawrence J , Dudbridge Frank , Spector Tim D , Wright Margaret J , Martin Nicholas G , McRae Allan F , Panicker Vijay , Zhu Gu , Walsh John P , Bell Jordana T , Wilson Scott G 
Published: January 2021

Abstract

Context
Circulating concentrations of free triiodothyronine (fT3), free thyroxine (fT4), and thyrotropin (TSH) are partly heritable traits. Recent studies have advanced knowledge of their genetic architecture. Epigenetic modifications, such as DNA methylation (DNAm), may be important in pituitary-thyroid axis regulation and action, but data are limited.

Objective
To identify novel associations between fT3, fT4, and TSH and differentially methylated positions (DMPs) in the genome in subjects from 2 Australian cohorts.

Method
We performed an epigenome-wide association study (EWAS) of thyroid function parameters and DNAm using participants from: Brisbane Systems Genetics Study (median age 14.2 years, n = 563) and the Raine Study (median age 17.0 years, n = 863). Plasma fT3, fT4, and TSH were measured by immunoassay. DNAm levels in blood were assessed using Illumina HumanMethylation450 BeadChip arrays. Analyses employed generalized linear mixed models to test association between DNAm and thyroid function parameters. Data from the 2 cohorts were meta-analyzed.

Results
We identified 2 DMPs with epigenome-wide significant (P &lt; 2.4E−7) associations with TSH and 6 with fT3, including cg00049440 in KLF9 (P = 2.88E−10) and cg04173586 in DOT1L (P = 2.09E−16), both genes known to be induced by fT3. All DMPs had a positive association between DNAm and TSH and a negative association between DNAm and fT3. There were no DMPs significantly associated with fT4. We identified 23 differentially methylated regions associated with fT3, fT4, or TSH.

Conclusions
This study has demonstrated associations between blood-based DNAm and both fT3 and TSH. This may provide insight into mechanisms underlying thyroid hormone action and/or pituitary-thyroid axis function.
The Relationship Between Glucose Control and Cognitive Function in People With Diabetes After a Lacunar Stroke
Authors: Cukierman-Yaffe Tali , McClure Leslie A , Risoli Thomas , Bosch Jackie , Sharma Mike , Gerstein Hertzel C , Benavente Oscar 
Published: January 2021

Abstract

Context
Lacunar strokes and diabetes are risk factors for cognitive dysfunction. Elucidating modifiable risk factors for cognitive dysfunction has great public health implications. One factor may be glycemic status, as measured by glycated hemoglobin (A1c).

Objective
The aim of this study was to assess the relationship between A1c and cognitive function in lacunar stroke patients with diabetes.

Methods
The effect of baseline and follow-up A1c on the baseline and the change in Cognitive Assessment Screening Instrument (CASI) score over time among participants with a median of 2 cognitive assessments (range, 1-5) was examined in 942 individuals with diabetes and a lacunar stroke who participated in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial (ClinicalTrials.gov No. NCT00059306).

Results
Every 1% higher baseline A1c was associated with a 0.06 lower standardized CASI z score (95% CI, –0.101 to –0.018). Higher baseline A1c values were associated with lower CASI z scores over time (P for interaction = .037). A 1% increase in A1c over time corresponded with a CASI score decrease of 0.021 (95% CI, –0.0043 to –0.038) during follow-up. All these remained statistically significant after adjustment for age, sex, education, race, depression, hypertension, hyperlipidemia, body mass index, cardiovascular disease, obstructive sleep apnea, diabetic retinopathy, nephropathy insulin use, and white-matter abnormalities.

Conclusion
This analysis of lacunar stroke patients with diabetes demonstrates a relationship between A1c and change in cognitive scores over time. Intervention studies are needed to delineate whether better glucose control could slow the rate of cognitive decline in this high-risk population.
Update on Novel Hormonal and Nonhormonal Male Contraceptive Development
Authors: Long Jill E , Lee Min S , Blithe Diana L 
Published: January 2021

AbstractBackgroundThe advent of new methods of male contraception would increase contraceptive options for men and women and advance male contraceptive agency. Pharmaceutical R&D for male contraception has been dormant since the 1990s. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) has supported a contraceptive development program since 1969 and supports most ongoing hormonal male contraceptive development. Nonhormonal methods are in earlier stages of development.ContentSeveral hormonal male contraceptive agents have entered clinical trials. Novel single agent products being evaluated include dimethandrolone undecanoate, 11β-methyl-nortestosterone dodecylcarbonate, and 7α-methyl-19-nortestosterone. A contraceptive efficacy trial of Nestorone®/testosterone gel is underway. Potential nonhormonal methods are at preclinical stages of development. Many nonhormonal male contraceptive targets that affect sperm production, sperm function, or sperm transport have been identified.SummaryNICHD supports development of reversible male contraceptive agents. Other organizations such as the World Health Organization, the Population Council, and the Male Contraception Initiative are pursuing male contraceptive development, but industry involvement remains limited.