bluuebunny/crossref_metadata_2025 huggingface dataset:
Generating high-fidelity synthetic time-to-event datasets to improve data transparency and accessibility
Authors: Smith Aiden , Lambert Paul C. , Rutherford Mark J.
Published: June 2022

Background

A lack of available data and statistical code being published alongside journal articles provides a significant barrier to open scientific discourse, and reproducibility of research. Information governance restrictions inhibit the active dissemination of individual level data to accompany published manuscripts. Realistic, high-fidelity time-to-event synthetic data can aid in the acceleration of methodological developments in survival analysis and beyond by enabling researchers to access and test published methods using data similar to that which they were developed on.

Methods

We present methods to accurately emulate the covariate patterns and survival times found in real-world datasets using synthetic data techniques, without compromising patient privacy. We model the joint covariate distribution of the original data using covariate specific sequential conditional regression models, then fit a complex flexible parametric survival model from which to generate survival times conditional on individual covariate patterns. We recreate the administrative censoring mechanism using the last observed follow-up date information from the initial dataset. Metrics for evaluating the accuracy of the synthetic data, and the non-identifiability of individuals from the original dataset, are presented.

Results

We successfully create a synthetic version of an example colon cancer dataset consisting of 9064 patients which aims to show good similarity to both covariate distributions and survival times from the original data, without containing any exact information from the original data, therefore allowing them to be published openly alongside research.

Conclusions

We evaluate the effectiveness of the methods for constructing synthetic data, as well as providing evidence that there is minimal risk that a given patient from the original data could be identified from their individual unique patient information. Synthetic datasets using this methodology could be made available alongside published research without breaching data privacy protocols, and allow for data and code to be made available alongside methodological or applied manuscripts to greatly improve the transparency and accessibility of medical research.
Direct arterial puncture for hemodialysis, a neglected but simple and valuable vascular access
Authors: Sun Chun-Yan , Zhong Mi , Song Li , Chen Ying-Gui , Quan Zi-lin , Zhao Li-Yan , Cui Dong-Mei , Fu Xia
Published: June 2022

Introduction

The purpose of this study is to present the prevalence and effects of direct arterial puncture (DAP) for hemodialysis patients, and to introduce optimal option for the vascular access (VA) in certain hemodialysis patients with poor condition of vascular or cardiac function in a compelling situation.

Methods

This was a cross-sectional study. Demographic characteristics and laboratory data were extracted from the health care system. Relevant DAP information was collected by a questionnaire. Case-control matching was performed to compare the hemodialysis adequacy between DAP and other VAs.

Results

A total of 526 patients were selected for analysis by convenience sampling, of which 38 patients relied on DAP for hemodialysis. The main reasons using DAP for hemodialysis included the cost of arteriovenous access creation or maintenance in 19(50%) patients and the poor condition of vascular or cardiac function in 14 (39.5%) patients. Some complications of DAP occurred, such as aneurysm or pseudoaneurysm in 16(42.1%) patients, infiltration in 12 (31.6%) patients. Differences in hemodialysis adequacy were not statistically significant between DAP and other types of VA.

Conclusion

In conclusion, DAP can meet the need of prescription hemodialysis, yet it has several limitations. Although the patients in our study were long-term dependent on DAP for hemodialysis with various reasons, we do not recommend DAP as a long-term vascular access if better options are available. However, DAP should not be overlooked to be a supplemental VA for hemodialysis with adequate blood flow and availability for individuals with poor condition of vascular or cardiac function in a compelling situation.
Association of β-cell function and cognitive impairment in patients with abnormal glucose metabolism
Authors: Guo Mengyi , Jia Jiaokun , Zhang Jia , Zhou Mingyue , Wang Anxin , Chen Shengyun , Zhao Xingquan
Published: June 2022

Background

Insulin has been demonstrated to play an important role in the occurrence and development of Alzheimer’s disease, especially in those with diabetes. β cells are important insulin-producing cells in human pancreas. This study aimed to investigate the association between β-cell dysfunction and cognitive impairment among patients over 40-year-old with abnormal glucose metabolism in Chinese rural communities.

Methods

A sample of 592 participants aged 40 years or older from the China National Stroke Prevention Project (CSPP) between 2015 and 2017 were enrolled in this study. Abnormal glucose metabolism was defined when hemoglobin Alc ≥ 5.7%. Cognitive function was assessed by the Beijing edition of the Montreal Cognitive Assessment scale. Homeostasis assessment of β-cell function was performed and classified into 4 groups according to the quartiles. A lower value of HOMA-β indicated a worse condition of β-cell function. Multivariate logistic regression was used to analyze the association between β-cell function and cognitive impairment.

Results

In a total of 592 patients with abnormal glucose metabolism, the average age was 60.20 ± 7.63 years and 60.1% patients had cognitive impairment. After adjusting for all potential risk factors, we found the first quartile of β-cell function was significantly associated with cognitive impairment (OR: 2.27, 95%CI: 1.32–3.92), especially at the domains of language (OR: 1.64, 95%CI: 1.01–2.65) and abstraction (OR: 2.29, 95%CI: 1.46–3.58).

Conclusions

Our study showed that worse β-cell function is associated with cognitive impairment of people over 40-year-old with abnormal glucose metabolism in Chinese rural communities, especially in the cognitive domains of abstraction and language.
Comprehensive bioinformatic analysis reveals a cancer-associated fibroblast gene signature as a poor prognostic factor and potential therapeutic target in gastric cancer
Authors: Ucaryilmaz Metin Cemre , Ozcan Gulnihal
Published: June 2022

Background

Gastric cancer is one of the deadliest cancers, currently available therapies have limited success. Cancer-associated fibroblasts (CAFs) are pivotal cells in the stroma of gastric tumors posing a great risk for progression and chemoresistance. The poor prognostic signature for CAFs is not clear in gastric cancer, and drugs that target CAFs are lacking in the clinic. In this study, we aim to identify a poor prognostic gene signature for CAFs, targeting which may increase the therapeutic success in gastric cancer.

Methods

We analyzed four GEO datasets with a network-based approach and validated key CAF markers in The Cancer Genome Atlas (TCGA) and The Asian Cancer Research Group (ACRG) cohorts. We implemented stepwise multivariate Cox regression guided by a pan-cancer analysis in TCGA to identify a poor prognostic gene signature for CAF infiltration in gastric cancer. Lastly, we conducted a database search for drugs targeting the signature genes.

Results

Our study revealed theCOL1A1, COL1A2, COL3A1, COL5A1, FN1, andSPARCas the key CAF markers in gastric cancer. Analysis of the TCGA and ACRG cohorts validated their upregulation and poor prognostic significance. The stepwise multivariate Cox regression elucidatedCOL1A1andCOL5A1, together withITGA4, Emilin1, andTSPAN9as poor prognostic signature genes for CAF infiltration. The search on drug databases revealed collagenaseclostridium histolyticum, ocriplasmin, halofuginone, natalizumab, firategrast, and BIO-1211 as the potential drugs for further investigation.

Conclusions

Our study demonstrated the central role of extracellular matrix components secreted and remodeled by CAFs in gastric cancer. The gene signature we identified in this study carries high potential as a predictive tool for poor prognosis in gastric cancer patients. Elucidating the mechanisms by which the signature genes contribute to poor patient outcomes can lead to the discovery of more potent molecular-targeted agents and increase the therapeutic success in gastric cancer.
An investigation of the control of quadriceps in people who are hypermobile; a case control design. Do the results impact our choice of exercise for people with symptomatic hypermobility?
Authors: Long Michael , Kiru Louise , Kassam Jamila , Strutton Paul H. , Alexander Caroline M.
Published: June 2022

Background

People with symptomatic hypermobility have altered proprioception however, the origin of this is unclear and needs further investigation to target rehabilitation appropriately. The objective of this investigation was to explore the corticospinal and reflex control of quadriceps and see if it differed between three groups of people: those who have symptomatic hypermobility, asymptomatic hypermobility and normal flexibility.

Methods

Using Transcranial Magnetic Stimulation (TMS) and electrical stimulation of peripheral nerves, motor evoked potentials (MEPs) and Hoffman (H) reflexes of quadriceps were evoked in the three groups of people. The threshold and latency of MEPs and the slope of the input–output curves and the amplitude of MEPs and H reflexes were compared across the groups.

Results

The slope of the input–output curve created from MEPs as a result of TMS was steeper in people with symptomatic hypermobility when compared to asymptomatic and normally flexible people (p = 0.04). There were no other differences between the groups.

Conclusion

Corticospinal excitability and the excitability at the motoneurone pool are not likely candidates for the origin of proprioceptive loss in people with symptomatic hypermobility. This is discussed in the light of other work to suggest the receptor sitting in hypermobile connective tissue is a likely candidate. This suggests that treatment aimed at improving receptor responsiveness through increasing muscle tone, may be an effective rehabilitation strategy.
Nurses’ perceptions of continuing professional development: a qualitative study
Authors: Yu Xiaoyan , Huang Yi , Liu Yu
Published: June 2022

Background

Continuing professional development is regarded as one of the important approaches to maintaining skills and motivation for work. However, there is a lack of qualitative studies to explore Chinese nurses’ continuing professional development. The study aims to explore Chinese nurses’ perceptions of continuing professional development and challenges they face.

Methods

The study was conducted in a tertiary hospital located in the central region of China from July to August 2020. Purposive sampling was used to recruit 14 nurses and face to face semi-structured interviews were conducted from July to August 2020. Then the recorded data were analysed and collated according to the thematic analysis. This study followed the consolidated criteria for reporting qualitative research (COREQ).

Results

Four themes were extracted: improving specialty ability; different development phases; the importance of personal effort; the obstacle of work-family conflict.

Conclusions

This study contributed to our understandings of nurses’ continuing professional development. Nurses held a positive attitude towards continuing professional development and they faced challenges in the meantime. Special attention and targeted supports should be provided to promote the continuing professional development of nursing staff.
Short and long-term prognosis of admission hyperglycemia in patients with and without diabetes after acute myocardial infarction: a retrospective cohort study
Authors: Upur Hanzohra , Li Jia-Li , Zou Xiao-Guang , Hu Yu-Ying , Yang He-Yin , Abudoureyimu Alimujiang , Abliz Anwar , Abdukerim Mamatili , Huang Min
Published: June 2022

Objective

Admission hyperglycemia is associated with poor prognosis in patients with acute myocardial infarction (AMI), but the effects of baseline diabetes status on this association remain elusive. We aim to investigate the impact of admission hyperglycemia on short and long-term outcomes in diabetic and non-diabetic AMI patients.

Methods

In this retrospective cohort study, 3330 patients with regard to first-time AMI between July 2012 and July 2020 were identified. Participants were divided into two groups according to diabetes status (1060 diabetic patients and 2270 non-diabetic patients). Thereafter, they were divided into four groups according to diabetes status-specific cutoff values of fasting blood glucose (FBG) identified by restricted cubic spline. Short-term outcomes included in-hospital death and cardiac complications. Long-term outcomes were all-cause mortality and major adverse cardiovascular events (MACE). Inverse probability of treatment weighting (IPTW) was conducted to adjust for baseline differences among the groups, followed by a weighted Cox proportional hazards regression analysis to calculate hazard ratios and 95% confidence intervals for all-cause mortality associated with each FBG category. Subgroup analysis and sensitivity analysis were performed to test the robustness of our findings.

Results

During a median follow-up of 3.2 years, 837 patients died. There was a significant interaction between diabetes status and FBG levels for all-cause mortality during long-term follow-up (p-interaction < 0.001). Moreover, restricted cubic spline curves for the association between FBG and all-cause mortality followed a J shape in patients with diabetes and a non-linear in patients without diabetes. Kaplan–Meier analysis demonstrated greater survival in non-hyperglycemia patients compared to hyperglycemia patients for both diabetic and non-diabetic patients groups. Survival of hyperglycemia patients without diabetes greater than in hyperglycemia patients with diabetes. In the weighted Multivariable cox analysis, admission hyperglycemia predicted higher short and long-term mortality. Subgroup analysis and sensitivity analysis showed the robustness of the results.

Conclusions

The inflection points of FBG level for poor prognosis were 5.60 mmol/L for patients without diabetes and 10.60 mmol/L for patients with diabetes. Admission hyperglycemia was identified as an independent predictor of worse short and long-term outcomes in AMI patients, with or without diabetes. These findings should be explored further.
Implementation and acceptance of government-sponsored malaria control interventions in Meghalaya, India
Authors: Passah Mattimi , Nengnong Carinthia Balabet , Wilson Mark L. , Carlton Jane M. , Kharbamon Larry , Albert Sandra
Published: June 2022

Background

India has made considerable progress in malaria reduction over the past two decades, with government-sponsored indoor residual spraying (IRS) and insecticide-treated bed net (ITN) or long-lasting insecticidal nets (LLIN) distribution being the main vector-related prevention efforts. Few investigations have used non-participant observational methods to assess malaria control measures while they were being implemented, nor documented people’s perceptions and acceptance of IRS or LLINs in India, and none have done so in the northeast region. This study evaluated household (HH)-level operation of IRS and distribution of LLINs by India’s National Vector Borne Disease Control Programme (NVBDCP) in 50 villages of Meghalaya state, and documented their acceptance and use.

Methods

Study field teams accompanied the government health system teams during August-October, 2019 and 2020 to observe deployment of LLINs, and record HH-level data on LLIN numbers and use. In addition, NVBDCP spray teams were followed during 2019–2021 to observe IRS preparation and administration. HH members were interviewed to better understand reasons for acceptance or refusal of spraying.

Results

A total of 8386 LLINs were distributed to 2727 HHs in 24 villages from five Primary Health Centres, representing 99.5% of planned coverage. Interviews with 80 HH residents indicated that they appreciated the LLIN dissemination programme, and generally made regular and appropriate use of LLINs, except during overnight travel or when working in agricultural fields. However, HH-level IRS application, which was observed at 632 HHs, did not always follow standard insecticide preparation and safety protocols. Of 1,079 occupied HHs visited by the spray team, 632 (58.6%) refused to allow any spraying. Only 198 (18.4%) HHs agreed to be sprayed, comprising 152 (14.1%) that were only partly sprayed, and 46 (4.3%) that were fully sprayed. Reasons for refusal included: inadequate time to rearrange HH items, young children were present, annoying smell, staining of walls, and threat to bee-keeping or Eri silk moth cultivation.

Conclusions

These findings are among the first in India that independently evaluate people's perceptions and acceptance of ongoing government-sponsored IRS and LLIN programmes for malaria prevention. They represent important insights for achieving India's goal of malaria elimination by 2030.
Comparison of two surgical approaches for acute type A aortic dissection: hybrid debranching versus total arch replacement
Authors: Huang Feng , Li Xiaofeng , Zhang Zili , Li Chunping , Ren Fei
Published: June 2022

Background

The goal of this study was to determine the clinical outcomes of total arch replacement with frozen elephant trunk surgery and hybrid debranching surgery for acute type A aortic dissection patients.

Methods

From January 2017 to December 2019, the clinical data of acute type A aortic dissection patients were retrospectively collected and analyzed. There were 142 patients underwent total arch replacement with frozen elephant trunk surgery and 35 patients underwent hybrid debranching surgery.

Result

The age, the body mass index and the renal insufficiency of patients in the hybrid group were higher than those in the total arch replacement (TAR) group (all P < 0.01). The operation time, the cardiopulmonary bypass time and the aortic occlusion time of patients in the TAR group were significantly longer than those in the hybrid group (all P < 0.01). Patients in the debranching group had shorter ventilator-assisted breathing time, shorter postoperative hospital stay time and shorter intensive care unit (ICU) stay time. The incidence of pulmonary infection and transient neurological dysfunction were lower, and the transfusions of red blood cells and plasma during the perioperative period were smaller. The survival rates at 2 years were 91.9% and 85.9% in the TAR and hybrid groups, respectively.

Conclusion

Hybrid debranching operation is a safe and effective method for acute type A aortic dissection. Compared with TAR surgery, hybrid debranching surgery has the characteristics of less trauma, rapid recovery and lower incidence of complication.
Fecal fermentation characteristics of Rheum tanguticum polysaccharide and its effect on the modulation of gut microbial composition
Authors: Wu Ding-Tao , Yuan Qin , Feng Kang-Lin , Zhang Jinming , Gan Ren-You , Zou Liang , Wang Shengpeng
Published: June 2022

Background

Rheum tanguticum is utilized as one of the well known traditional Chinese medicine for the treatment of gastrointestinal diseases. Recently, R. tanguticum polysaccharides (RP) have received increasing attention due to their diversely pharmacological activities. Usually, the pharmacological activities of polysaccharides are closely correlated to their metabolic properties from the stomach to the intestine. However, the digestive behavior and fecal fermentation characteristics of RP are unknown, which need to be fully investigated.

Methods

In this study, an in vitro simulated gastrointestinal model was carried out for the investigation of the digestive behavior and fecal fermentation characteristics of RP. The possible changes in physicochemical properties of RP, such as molecular weight, monosaccharide composition, reducing sugar released, chemical composition, pH value, and short chain fatty acids, were determined during in vitro simulated digestion and human fecal fermentation, and its effect on the modulation of gut microbial composition was also evaluated.

Results

The results revealed that RP was indigestible under the in vitro simulated digestion conditions according to its stabilities in physicochemical properties. Conversely, the indigestible RP (RPI) could be notably utilized by colonic microbiota in human feces after the in vitro fermentation, especially, at the initial fermentation stage (0–6 h). The fecal fermentation characteristics of RPI were revealed. Results showed that the content of reducing sugars obviously increased from 0.177 to 0.778 mg/mL at the initial stage of fermentation, and its molecular weight notably declined from 2.588 × 105 to 0.828 × 105 Da at the end stage of fermentation. Notably, the utilization of arabinose and galactose in RPI by colonic bacteria was faster than that of galacturonic acid. Besides, RPI could obviously modulate gut microbial composition via promoting the relative abundances of several beneficial bacteria, such as genera Bacteroides, Bifidobacterium, and Megamonas, resulting in the promoted production of several short-chain fatty acids, such as acetic, propionic, and butyric acids.

Conclusions

Results from this study showed that RP was indigestible in the human upper gastrointestinal tract in vitro, but could be easily utilized by colonic microbiota in human feces at the initial stage of fermentation. RP could be used as potential prebiotics for the improvement of intestinal health.
Users' passivity in accessing digested scientific evidence through social media: cross-sectional insights
Authors: Machado Gabriela M. , Braga Mariana M.
Published: June 2022

Objectives

This manuscript provides novel insights about the potential use of social media (a Facebook page, the first strategic attempt by EviDent initiative) to share evidence-based dentistry content and empowerment strategies for professionals, using quantifiable usage metrics, besides exposing the strengths and weaknesses of this knowledge translation strategy. One year-long gathered metrics were analyzed to understand information about usage patterns.

Results

Publications were potentially exposed to 4784 users, and subsequent interaction with the page occurred in 18% of cases. Users' involvement with page content was associated with the number of page visitors (P = .005). However, users' interaction with the page was not associated with the potential number of users that could have seen the page (P = .25). Even considering the users that approved the posts, only 7%, on average, interacted with the post's links. Although social media has effectively disseminated scientific content, our experience revealed the user's passivity in interacting with the content. We expect to overcome these barriers by developing a mobile app to offer a more interactive and dynamic interface associated with a more attractive format for posting, including images and infographics.
Effect of positioning and expiratory rib-cage compression on atelectasis in a patient who required prolonged mechanical ventilation: a case report
Authors: Hosoe Takuya , Tanaka Tsuyoshi , Hamasaki Honoka , Nonoyama Kotomi
Published: June 2022

Background

Pulmonary complications can be caused by intraoperative mechanical ventilation. In particular, prolonged mechanical ventilation is associated with a high mortality rate, a risk of pulmonary complications, prolonged hospitalization, and an unfavorable discharge destination. Pre- and postoperative rehabilitation are important for the resolution of pulmonary complications in acute cases. However, there has been a lack of studies on interventions for pulmonary rehabilitation of patients with chronic pulmonary complications caused by prolonged mechanical ventilation. Accordingly, we describe the effect of pulmonary rehabilitation in such a patient.

Case presentation

We examined a 63-year-old Japanese woman with hypoxic–ischemic encephalopathy after subarachnoid hemorrhage who required prolonged mechanical ventilation. Radiographic and computed tomographic images revealed atelectasis of the right upper lobe. In addition, this atelectasis reduced the tidal volume, minute volume, and oxygen saturation and caused an absence of breath sounds in the right upper lobe during auscultation. We aimed to ameliorate the patient’s atelectasis and improve her ventilation parameters by using positioning and expiratory rib-cage compression after endotracheal suctioning. Specifically, the patient was seated in Fowler’s position, and mild pressure was applied to the upper thorax during expiration, improving her inspiratory volume. Immediately, breath sounds were audible in the right upper lobe. Furthermore, resolution of the patient’s atelectasis was confirmed with chest radiography performed on the same day. In addition, her ventilation parameters (tidal volume, minute volume, and oxygen saturation) improved.

Conclusions

Our results indicate that physical therapists should consider application of specific positioning and expiratory rib-cage compression in patients who exhibit atelectasis because of prolonged mechanical ventilation.
A patient with familial Mediterranean fever mimicking diarrhea-dominant irritable bowel syndrome who successfully responded to treatment with colchicine: a case report
Authors: Kumei Shima , Ishioh Masatomo , Murakami Yuki , Ando Katsuyoshi , Nozu Tsukasa , Okumura Toshikatsu
Published: June 2022

Background

Irritable bowel syndrome is a functional gastrointestinal disease. Visceral hypersensitivity is the most important pathophysiology in irritable bowel syndrome. Currently, diagnosis of irritable bowel syndrome is based on symptoms and exclusion of other organic diseases. Although the diagnosis of irritable bowel syndrome can be made based on the Rome IV criteria, one may speculate that complete exclusion of other organic diseases is not so easy, especially in cases uncontrolled with standard therapies.

Case presentation

We present herein a case of familial Mediterranean fever in a young Japanese patient who had been suffering from an irritable bowel syndrome-like clinical course. A 25-year-old Japanese male had been diagnosed as having diarrhea-predominant irritable bowel syndrome 5 years earlier. Unfortunately, standard therapies failed to improve irritable bowel syndrome symptoms. After careful medical history-taking, we understood that he had also experienced periodic fever since 10 years ago. Although no mutation was identified in the Mediterranean fever gene, not only periodic fever but abdominal symptoms improved completely after colchicine administration. He was therefore diagnosed as having familial Mediterranean fever and that the abdominal symptoms may be related to the disease.

Conclusions

Familial Mediterranean fever should be considered as a cause of irritable bowel syndrome-like symptoms.
Metabolic sensor O-GlcNAcylation regulates erythroid differentiation and globin production via BCL11A
Authors: Luanpitpong Sudjit , Kang Xing , Janan Montira , Thumanu Kanjana , Li Jingting , Kheolamai Pakpoom , Issaragrisil Surapol
Published: June 2022

Background

Human erythropoiesis is a tightly regulated, multistep process encompassing the differentiation of hematopoietic stem cells (HSCs) toward mature erythrocytes. Cellular metabolism is an important regulator of cell fate determination during the differentiation of HSCs. However, howO-GlcNAcylation, a posttranslational modification of proteins that is an ideal metabolic sensor, contributes to the commitment of HSCs to the erythroid lineage and to the terminal erythroid differentiation has not been addressed.

Methods

CellularO-GlcNAcylation was manipulated using small molecule inhibition or CRISPR/Cas9 manipulation of catalyzing enzymeO-GlcNAc transferase (OGT) and removing enzymeO-GlcNAcase (OGA) in two cell models of erythroid differentiation, starting from: (i) human umbilical cord blood-derived CD34+hematopoietic stem/progenitor cells (HSPCs) to investigate the erythroid lineage specification and differentiation; and (ii) human-derived erythroblastic leukemia K562 cells to investigate the terminal differentiation. The functional and regulatory roles ofO-GlcNAcylation in erythroid differentiation, maturation, and globin production were investigated, and downstream signaling was delineated.

Results

First, we observed that two-step inhibition of OGT and OGA, which were established from the observed dynamics ofO-GlcNAc level along the course of differentiation, promotes HSPCs toward erythroid differentiation and enucleation, in agreement with an upregulation of a multitude of erythroid-associated genes. Further studies in the efficient K562 model of erythroid differentiation confirmed that OGA inhibition and subsequent hyper-O-GlcNAcylation enhance terminal erythroid differentiation and affect globin production. Mechanistically, we found that BCL11A is a key mediator ofO-GlcNAc-driven erythroid differentiation and β- and α-globin production herein. Additionally, analysis of biochemical contents using synchrotron-based Fourier transform infrared (FTIR) spectroscopy showed unique metabolic fingerprints upon OGA inhibition during erythroid differentiation, supporting that metabolic reprogramming plays a part in this process.

Conclusions

The evidence presented here demonstrated the novel regulatory role ofO-GlcNAc/BCL11A axis in erythroid differentiation, maturation, and globin production that could be important in understanding erythropoiesis and hematologic disorders whose etiology is related to impaired erythroid differentiation and hemoglobinopathies. Our findings may lay the groundwork for future clinical applications toward an ex vivo production of functional human reticulocytes for transfusion from renewable cell sources, i.e., HSPCs and pluripotent stem cells.
Impact of volcanic ash from Cotopaxi-2015 and Tungurahua-2016 eruptions on the dielectric characteristics of suspension insulators, Ecuador
Authors: Ramírez Juan , Vasconez Francisco J. , López Alex , Valencia Fausto , Quilumba Franklin , Vásconez Müller Anais , Hidalgo Silvana , Bernard Benjamin
Published: June 2022

In Ecuador, a country with several active volcanoes and with four eruptions in the last decade in the continental arc, it is very likely that high-voltage transmission lines cross volcanic hazard zones on their routes. Here, we quantify the impact of fresh volcanic ash from the hydromagmatic Cotopaxi-2015 and the magmatic Tungurahua-2016 eruptions on the dielectric characteristics of ANSI 52–3 suspension insulators made of porcelain and glass, under moist conditions. The experiments include two methodologies to measure the performance of the insulators in real-time: the minimum insulator flashover voltage (FOVmin) and the dielectric loss factor angle. Both allow quantifying i) the critical voltage that the insulators can withstand prior to flashover occurrence and, ii) the strong fluctuating behavior that the insulators undergo in an ashy environment. Based on six contamination scenarios, we found that there is a higher chance of flashover if the insulators are completely blanketed (top and bottom) even with a fine ash layer (1 mm), than if they are covered just at the top. Our results further show that the ash of Cotopaxi-2015 eruption has a higher chance of leading to insulator failure because of its higher conductivity (i.e. higher leachate content) than that of Tungurahua-2016. Additionally, we identify two critical voltages prior to electrical flashover on the insulators of 28.25 kV and 17.01 kV for the 230 kV and 138 kV Ecuadorian transmission lines, respectively. Finally, we present a simple impact evaluation for the main Ecuadorian transmission lines based on the outcomes of this research and the official volcanic hazard maps for Cotopaxi and Tungurahua volcanoes.
Gene variations of glutamate metabolism pathway and epilepsy
Authors: Feng Yan , Zhang Cuirong , Wei Zihan , Li Guoyan , Gan Yajing , Liu Chao , Deng Yanchun
Published: June 2022

Background

Epilepsy is a paroxysmal disorder of the brain, caused by an imbalance of neuronal excitation and inhibition. Glutamate is the most important excitatory neurotransmitter in the brain and plays an important role in epileptogenesis. Mutations in genes at any step/component of the glutamate metabolic pathway may lead to the development of epilepsy or epileptic encephalopathy.

Methods

Clinical history of 3 epilepsy patients with genetic variations of the glutamate metabolism pathway was collected. Electroencephalogram recording and magnetic resonance imaging  were performed in each patient. We also reviewed recent literature for a variety of the genetic variations involved in epilepsy.

Results

Case 1 was a SLC1A2 mutation-carrier diagnosed with developmental and epileptic encephalopathy (DEE) 41, whose seizures decreased after start of the ketogenic diet. Case 2 carried a GRIN2A gene mutation and was seizure-free for three years after taking levetiracetam and vitamin B6. Case 3 was a GRIN2B mutation-carrier  diagnosed with DEE 27, who seizures diminished after taking oxcarbazepine.

Conclusions

Preclinical and clinical evidence supports the therapeutic potential of glutamatergic signaling-targeting treatments for epilepsy. More studies are needed to discover novel DEE-related genetic mutations in the glutamate metabolic pathway.
Preserving signal during random noise attenuation through migration enhancement and local orthogonalization
Authors: Li Chao , Zhang Jinhai
Published: June 2022

Denoising methods are usually imperfect, causing some signal leakage in the residual data. The local orthogonalization method is powerful for retrieving the leaked signal; however, its original implementation could not effectively retrieve weak residual because the residual data have weak similarity. We develop a process for extracting weak signal by the local orthogonalization method in the migrated domain and then eliminating artifacts and compensating amplitude with two more rounds of local orthogonalization in the original domain. In the migrated domain, the weak signal can be enhanced by energy focusing, but the random noise cannot be systematically enhanced, which allows us to retrieve most of the residual signal using local orthogonalization. After demigrating the retrieved weak signal back to the original domain, we may encounter artifacts caused by the false focus of random noise in the migrated domain. Therefore, we perform the second round of local orthogonalization between the current and initial denoised results to eliminate these artifacts. We further compensate for the amplitude loss caused by migration and demigration using the third round of local orthogonalization between the updated signal and noise sections. Numerical experiments illustrate the superiority of our method over existing methods for retrieving the weak signal for pre- and poststack seismic profiles and ground-penetrating radar data.
Durvalumab Plus Olaparib in Previously Untreated, Platinum-Ineligible Patients With Metastatic Urothelial Carcinoma: A Multicenter, Randomized, Phase II Trial (BAYOU)
Authors: Rosenberg Jonathan E. , Park Se Hoon , Kozlov Vadim , Dao Tu V. , Castellano Daniel , Li Jian-Ri , Mukherjee Som D. , Howells Kathryn , Dry Hannah , Lanasa Mark C. , Stewart Ross , Bajorin Dean F.
Published: June 2022

PURPOSE

Homologous recombination repair gene mutations (HRRm) are common in urothelial carcinoma (UC), rendering tumor cells sensitive to poly (ADP-ribose) polymerase (PARP) inhibition. We assessed efficacy and safety of durvalumab (anti–programmed cell death ligand-1) plus olaparib (PARP inhibitor) in patients with metastatic UC (mUC).

METHODS

This randomized, multicenter, double-blind, phase II trial enrolled untreated, platinum-ineligible patients with mUC. Patients (N = 154) were randomly assigned 1:1 to receive durvalumab (1,500 mg intravenously once every 4 weeks) plus olaparib (300 mg orally, twice daily) or durvalumab plus placebo. The primary end point was progression-free survival (PFS) assessed by investigators per RECIST version 1.1. Secondary end points included overall survival in all patients and PFS in patients with HRRm.

RESULTS

Overall, median PFS was 4.2 months (95% CI, 3.6 to 5.6) for durvalumab plus olaparib and 3.5 months (95% CI, 1.9 to 5.1) for durvalumab plus placebo (hazard ratio [HR], 0.94; 95% CI, 0.64 to 1.39; log-rank P value, .789). Median overall survival was 10.2 months (95% CI, 7.0 to 13.9) and 10.7 months (95% CI, 7.2 to 17.3), respectively (HR, 1.07; 95% CI, 0.72 to 1.61). In the 20% of patients with HRRm, median PFS was 5.6 months (95% CI, 1.9 to 8.1) and 1.8 months (95% CI, 1.7 to 2.2), respectively (HR, 0.18; 95% CI, 0.06 to 0.47). Treatment-related grade 3 or 4 adverse events occurred in 18% and 9% of patients, respectively.

CONCLUSION

Adding olaparib to durvalumab did not improve survival outcomes in an unselected mUC population. Efficacy outcomes with durvalumab were similar to those reported for other anti–programmed cell death-1/programmed cell death ligand-1 agents. However, the results of secondary analyses suggest a potential role for PARP inhibition in patients with UC harboring HRRm.
“Electrical Nutrition and Glandular Control”: Eugenics, Progressive Science, and George Schuyler’sBlack No More
Authors: Adams Kim
Published: June 2022

In 1931, African American journalist George Schuyler imagined a medical treatment that could turn Black people white and American politics upside down. Schuyler’s novel, Black No More, uses this fictional race-altering technology to mount a satirical critique of progressive era investment in eugenic science as a tool of social reform. The novel draws on popular scientific theories of human perfection—electric medicine, hygienic nutrition, and glandular theory—to envision a mode of technological reproduction that troubles eugenic theories of biological inheritance and parodies the progressive marriage of politics and science. In reading Schuyler’s contrarian engagement with American race science through the novel’s use of medical technology, the essay extends critical discourse on the relationship between eugenics, progressive politics, and racial uplift in the early twentieth century. Bringing the politics of the past to bear on the present, it advances a critique of the persistent cultural legacy of progressive era scientific thought.
Elizabeth Bishop and the New Deal: Queer Poetics and the Welfare State in Key West
Authors: Strand Eric
Published: June 2022

Although our recovery of Elizabeth Bishop’s politics has involved seeing her as a resistant “outsider,” this essay argues that she was at her most challenging as an inhabitant of poetic institutions. Exemplifying the vexed status of the Depression-era writer after the crash of the patronage system, when Bishop settled in Key West, Florida, she was moving not to a cultural periphery but to a showpiece for government-sponsored social reform, where some of her most successful poems were stimulated by federal government policies. This productive interaction with agencies like the Federal Writers’ Project was cut short by World War II and by the sort of conservative backlash to the New Deal that drove the House Committee on Un-American Activities to investigate events leading to the postwar construction of an apolitical Bishop, abstracted from the politics that in fact conditioned much of her work. Ultimately, the essay suggests that relocating Bishops’s work in its New Deal context helps us see that, as one critic put it, “There’s something queer about the welfare state.”
Power Output Manipulation from Below to Above the Gas Exchange Threshold Results in Exacerbated Performance Fatigability
Authors: BROWNSTEIN CALLUM G. , PASTOR FREDERIC SABATER , MIRA JOSÉ , MURIAS JUAN M. , MILLET GUILLAUME Y.
Published: June 2022

Introduction

Performance fatigability is substantially greater when exercising in the severe- versus heavy-intensity domain. However, the relevance of the boundary between moderate- and heavy-intensity exercise, the gas exchange threshold (GET), to performance fatigability is unclear. This study compared alterations in neuromuscular function during work-matched exercise above and below the GET.

Methods

Seventeen male participants completed work-matched cycling for 90, 110, and 140 min at 110%, 90%, and 70% of the GET, respectively. Knee extensor isometric maximal voluntary contraction (MVC), high-frequency doublets (Db100), low- to high-frequency doublet ratio (Db10:100), and voluntary activation were measured at baseline, 25%, 50%, 75%, and 100% of task completion. During the initial baseline visit and after each constant work rate bout, ramp-incremental exercise was performed, and peak power output and oxygen uptake (V̇O2peak) were determined.

Results

After the 70% and 90% GET trials, similar reductions in MVC (−14% ± 6% and −14% ± 8%, respectively, P = 0.175) and Db100 (−7% ± 9% and −6% ± 9%, respectively, P = 0.431) were observed. However, for a given amount of work completed, reductions in MVC (−25% ± 15%, P = 0.008) and Db100 (−12% ± 8%, P = 0.029) were up to 2.6-fold greater during the 110% than the 90% GET trial. Peak power output and V̇O2peak during ramp-incremental exercise were reduced by 7.0% ± 11.3% and 6.5% ± 9.3%, respectively, after the 110% GET trial relative to the baseline ramp (P ≤ 0.015), with no changes after the moderate-intensity trials (P ≥ 0.078).

Conclusions

The lack of difference in fatigability between the trials at 70% and 90% GET, coupled with the greater fatigability at 110% relative to 90% GET, shows that exceeding the moderate- to heavy-intensity boundary has implications for performance fatigability, while also impairing maximal exercise performance capacity.
Η μεγάλη επιστροφή; Η προγραμματική εξέλιξη της ελληνικής ριζοσπαστικής Αριστεράς σε συγκριτική προοπτική (1980-2015)
Authors: Σπυροπούλου Παρασκευή
Published: June 2022

Στόχος της παρούσας διατριβής είναι η μελέτη της εξέλιξης του προγραμματικούλόγου της ριζοσπαστικής Αριστεράς στην Ελλάδα από το 1980 έως το 2015. Κεντρικόερώτημααποτελεί το αν τα κόμματα της ριζοσπαστικής Αριστεράς στην Ελλάδαδιατηρούν τις προγραμματικές κατευθύνσεις και τις ιδεολογικές καταβολές τωνπροκατόχων τους ή αν παρουσιάζουν αξιοσημείωτες αλλαγές.Χρησιμοποιώντας την ερευνητική μέθοδο της ποιοτικής ανάλυσηςπεριεχομένου εξετάζεται ο προγραμματικός λόγος των κομμάτων ΚΚΕ Εσωτερικούκαι της μετεξέλιξής του σε Ελληνική Αριστερά (ΕΑΡ), του Συνασπισμού τηςΑριστεράς, των Κινημάτων και της Οικολογίας (ΣΥΝ) και του Συνασπισμού τηςΡιζοσπαστικής Αριστεράς (ΣΥΡΙΖΑ) στη βάση πέντε αξόνων ανάλυσης: Οικονομία,Ευρώπη / Ευρωπαϊκή Ένωση, Κοινωνικό Κράτος,Πολιτισμικός Φιλελευθερισμός καιΙδεολογία. Ακολούθως, αναδεικνύεται η εξέλιξη, οι συνέχειες και οι τομές στονπρογραμματικό λόγο της ριζοσπαστικής Αριστεράς, λαμβάνοντας υπόψη τον τρόποπου επέδρασαν η παγκόσμια οικονομική κρίση του 2009 και το Δημοψήφισμα στηνΕλλάδα τον Ιούλιο του 2015. Τέλος, υποστηρίζεται ότι η ιδεολογία της ριζοσπαστικήςΑριστεράς στην Ελλάδα συνιστά μία σύνθεση παλαιών προϋπαρχόντων στοιχείων καινέων. Ο κεντρικός ιδεολογικός/προγραμματικός πυρήνας των ΚΚΕ Εσωτερικού /ΕΑΡ παραμένει, με παραλλαγές, σταθερός και επηρεάζει τις ιδεολογικές,προγραμματικές και αξιακές επιλογές του ΣΥΝ/ΣΥΡΙΖΑ. Ταυτόχρονα, ο ΣΥΝ και -περισσότερο - ο ΣΥΡΙΖΑ συνιστούν ριζοσπαστικοποιημένη εκδοχή και μετεξέλιξητης αξιακής – ιδεολογικής τους μήτρας που είναι το ΚΚΕ Εσωτερικού / ΕΑΡ.Λέξεις κλειδιά: Ριζοσπαστική Αριστερά, προγραμματικός λόγος, ΚΚΕ Εσωτερικού, ΣΥΝ,ΣΥΡΙΖΑ, Ελληνική Ανανεωτική Αριστερά
Search for supersymmetric particles with compressed mass spectrum in proton-proton collisions at a centre-of-mass energy of 13 TeV
Authors: Βουρλιώτης Εμμανουήλ
Published: June 2022

To κύριο αντικείμενο της διατριβής είναι η πειραματική διερεύνηση της Υπερσυμμετρίας (Supersymmetry, SUSY) σε συγκρούσεις πρωτονίων με ενέργεια κέντρου μάζας 13 TeV. Τα δεδομένα συλλέχθηκαν από το πείραμα Compact Muon Solenoid (CMS) κατά τη διάρκεια του Run 2 (2016–2018) του επιταχυντή Large Hadron Collider (LHC), και αντιστοιχούν σε συνολική φωτεινότητα μέχρι και 137 fb^(-1). Η ανάλυση εστιάζεται σε τελικές καταστάσεις με δύο ή τρία λεπτόνια (ηλεκτρόνια ή μιόνια) με χαμηλή εγκάρσια ορμή (pT), τουλάχιστον ένα ζεύγος εκ των οποίων έχει αντίθετο φορτίο και ίδια γεύση, και ελλείπουσα εγκάρσια ορμή. Τέτοιες υπογραφές μπορούν να παραχθούν σε μοντέλα SUSY με electroweakinos ή top squarks με συμπιεσμένο φάσμα μάζας, δηλαδή μικρές διαφορές μάζας μεταξύ των ελαφρύτερων υπερσυμμετρικών σωματιδίων. Τα αποτελέσματα της ανάλυσης είναι σε συμφωνία με τις προβλέψεις του Καθιερωμένου Προτύπου και χρησιμοποιούνται για την εξαγωγή ορίων αποκλεισμού στις μάζες των υπερσυμμετρικών σωματιδίων. Ένα σημαντικό τμήμα της διατριβής αφιερώνεται επίσης στην ανάπτυξη αλγορίθμων καθώς και του αντίστοιχου software και firmware για την Phase 2 αναβάθμιση (για το High-Luminosity LHC) του συστήματος σκανδαλισμού πρώτου επιπέδου (L1T) του CMS. Αρχικά, εξάγονται μια σειρά από διορθώσεις για L1T μιόνια, τα οποία καταγράφηκαν από τον demonstrator του Phase 2 L1T scouting συστήματος. Ακολούθως, παρουσιάζεται ένας multivariate αλγόριθμος που αναπτύχθηκε με στόχο την ταυτοποίηση ηλεκτρομαγνητικών, αδρονικών και pile-up σημάτων από το μελλοντικό καλορίμετρο «High Granularity» του CMS στο υποσύστημα L1T Correlator. Συζητείται επίσης ένας από τους αλγορίθμους οργάνωσης των δεδομένων του L1T Correlator, ο αλγόριθμος “deregionizer”, και παρουσιάζονται μελέτες για βελτιώσεις του. Τέλος, περιγράφεται η ανάπτυξη ενός firmware module για την ταξινόμηση των ηλεκτρομαγνητικών φυσικών αντικειμένων του L1T Correlator σύμφωνα με την εγκάρσια ορμή τους.
Κοινωνικοοικονομική διερεύνηση παραγόντων υιοθέτησης καινοτόμου γαλακτοκομικού προϊόντος του αγροδιατροφικού κλάδου
Authors: Τσιμήτρη Παρασκευή
Published: June 2022

Η παρούσα διατριβή επικεντρώθηκε στη διερεύνηση της αποδοχής και της προθυμίας υιοθέτησης ενός καινοτόμου προϊόντος από τα υπολείμματα του αγροδιατροφικού κλάδου. Συγκεκριμένα, ο κύριος στόχος της διατριβής επετεύχθη μέσα από τη μελέτη τριών κλιμάκων: α) της Κλίμακας Νεοφοβίας των Τροφίμων (Food Neophobia Scale-FNS), β) της Κλίμακας Νεοφοβίας της Τεχνολογίας των Τροφίμων (Food Technology Neophobia Scale-FTNS) και γ) της Κλίμακας Καινοτομικότητας (Domain-Specic Innovativeness-DSI), σε συνδυασμό με την ανάλυση μίας μελέτης περίπτωσης η οποία βασίστηκε σε ένα υποθετικό σενάριο. Για το σκοπό αυτό πραγματοποιήθηκε δειγματοληπτική έρευνα στο Πολεοδομικό Συγκρότημα Θεσσαλονίκης. Αρχικά διενεργήθηκε ποιοτική έρευνα, κι έπειτα, ποσοτική ανάλυση με 384 προσωπικές συνεντεύξεις. Τα δεδομένα που συγκεντρώθηκαν και το λοιπό υλικό αξιοποιήθηκε και επεξεργάστηκε με Απλές Περιγραφικές αλλά και με Πολυμεταβλητές Στατιστικές Αναλύσεις. Ειδικότερα, εφαρμόστηκε Διβηματική Ανάλυση σε Συστάδες (Two-Step Cluster Analysis) για την τμηματοποίηση του πληθυσμού σύμφωνα με το βαθμό καινοτομικότητας και το βαθμό νεοφοβίας και τεχνοφοβίας του πληθυσμού. Ακολούθως, τμηματοποιήθηκε το δείγμα σε ομάδες με κοινά χαρακτηριστικά και συμπεριφορά προκειμένου να εξεταστεί η συμβατότητα με τη θεωρία υιοθέτησης καινοτομιών του Rogers και περιεγράφηκε το προφίλ των δυνητικά τελικών χρηστών του καινοτόμου προϊόντος καθώς επίσης μελετήθηκαν οι παράγοντες αποδοχής ή απόρριψης του καινοτόμου προϊόντος. Σε κάθε εφαρμογή της Διβηματικής Ανάλυσης σε Συστάδες εφαρμόστηκε το μοντέλο της Κατηγορικής Παλινδρόμησης (Categorical Regression) προκειμένου να διερευνηθεί η σχέση μεταξύ των δημογραφικών και λοιπών χαρακτηριστικών και της εκάστοτε τμηματοποίησης. Η παρούσα διατριβή συγχρηματοδοτήθηκε από το Ευρωπαϊκό Ερευνητικό Πρόγραμμα “Sybawhey-Industrial symbiosis for valorising whey and banana wastes and by-products for the production of novel foods”, στο πλαίσιο της δράσης Marie Skłodowska-Curie (MSCA)-RISE 2015.