bluuebunny/crossref_metadata_2025 huggingface dataset:
DASSI: differential architecture search for splice identification from DNA sequences
Authors: Moosa Shabir , Amira Prof. Abbes , Boughorbel Dr. Sabri
Published: February 2021

Background

The data explosion caused by unprecedented advancements in the field of genomics is constantly challenging the conventional methods used in the interpretation of the human genome. The demand for robust algorithms over the recent years has brought huge success in the field of Deep Learning (DL) in solving many difficult tasks in image, speech and natural language processing by automating the manual process of architecture design. This has been fueled through the development of new DL architectures. Yet genomics possesses unique challenges that requires customization and development of new DL models.

Methods

We proposed a new model, DASSI, by adapting a differential architecture search method and applying it to the Splice Site (SS) recognition task on DNA sequences to discover new high-performance convolutional architectures in an automated manner. We evaluated the discovered model against state-of-the-art tools to classify true and false SS in Homo sapiens (Human), Arabidopsis thaliana (Plant), Caenorhabditis elegans (Worm) and Drosophila melanogaster (Fly).

Results

Our experimental evaluation demonstrated that the discovered architecture outperformed baseline models and fixed architectures and showed competitive results against state-of-the-art models used in classification of splice sites. The proposed model - DASSI has a compact architecture and showed very good results on a transfer learning task. The benchmarking experiments of execution time and precision on architecture search and evaluation process showed better performance on recently available GPUs making it feasible to adopt architecture search based methods on large datasets.

Conclusions

We proposed the use of differential architecture search method (DASSI) to perform SS classification on raw DNA sequences, and discovered new neural network models with low number of tunable parameters and competitive performance compared with manually engineered architectures. We have extensively benchmarked DASSI model with other state-of-the-art models and assessed its computational efficiency. The results have shown a high potential of using automated architecture search mechanism for solving various problems in the field of genomics.
Extracting single-trial neural interaction using latent dynamical systems model
Authors: Huh Namjung , Kim Sung-Phil , Lee Joonyeol , Sohn Jeong-woo
Published: February 2021

In systems neuroscience, advances in simultaneous recording technology have helped reveal the population dynamics that underlie the complex neural correlates of animal behavior and cognitive processes. To investigate these correlates, neural interactions are typically abstracted from spike trains of pairs of neurons accumulated over the course of many trials. However, the resultant averaged values do not lead to understanding of neural computation in which the responses of populations are highly variable even under identical external conditions. Accordingly, neural interactions within the population also show strong fluctuations. In the present study, we introduce an analysis method reflecting the temporal variation of neural interactions, in which cross-correlograms on rate estimates are applied via a latent dynamical systems model. Using this method, we were able to predict time-varying neural interactions within a single trial. In addition, the pairwise connections estimated in our analysis increased along behavioral epochs among neurons categorized within similar functional groups. Thus, our analysis method revealed that neurons in the same groups communicate more as the population gets involved in the assigned task. We also showed that the characteristics of neural interaction from our model differ from the results of a typical model employing cross-correlation coefficients. This suggests that our model can extract nonoverlapping information about network topology, unlike the typical model.
CD19 CAR-T expressing PD-1/CD28 chimeric switch receptor as a salvage therapy for DLBCL patients treated with different CD19-directed CAR T-cell therapies
Authors: Liang Yun , Liu Hui , Lu Zheming , Lei Wen , Zhang Chaoting , Li Ping , Liang Aibin , Young Ken H. , Qian Wenbin
Published: February 2021

CD19-targeted chimeric antigen receptor T (CAR T) cell therapy is a promising option to treat relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). However, the majority of CAR T-treated patients will eventually progress and require salvage treatment, for which there is no current standard. In this study, we analyzed data from 6 patients with R/R DLBCL who experienced progression following CD19-CAR T therapy, and then received CD19-specific CAR T cells that express a PD-1/CD28 chimeric switch-receptor (CD19-PD-1/CD28-CAR T) as salvage therapy at our institution. After the second infusion of CAR T cells, 3 of 6 patients achieved complete remissions and the duration of the response of responsive patients ranged from 8 to 25 months. One patient showed a stable disease. In contrast, 2/6 patients died on 60 days because of progression disease. Importantly, no severe neurologic toxicity or cytokine release syndrome was observed. These data suggest that CD19-PD-1/CD28-CAR-T cells, a novel anti-CD19 CAR-T cell therapy, elicit a potent and durable anticancer response, and can be used in the post-CD19-CAR T failure setting.
Incidental finding of APC deletion in a child: double trouble or double chance? – a case report
Authors: Rosina Erica , Rinaldi Berardo , Silipigni Rosamaria , Bergamaschi Luca , Gattuso Giovanna , Signoroni Stefano , Guerneri Silvana , Carnevali Alessandra , Marchisio Paola Giovanna , Milani Donatella
Published: February 2021

Background

22q11.2 deletion syndrome is one of the most common genomic disorders, characterized by the variable presence of facial dysmorphisms, congenital cardiac defects, velopharyngeal insufficiency/cleft palate, thymic hypoplasia/aplasia, immunodeficiency, parathyroid hypoplasia, developmental delay, learning disabilities, psychiatric disorders, renal, ocular, and skeletal malformations, hearing loss and laryngeal abnormalities. Chromosomal microarray (CMA) hybridization is one of the most performed diagnostic tests but as a genome wide analysis, it can point out relevant incidental copy number variations.

Case presentation

We report the case of a 2-year-old boy that came to our attention for mild psychomotor delay, poor growth, and minor facial anomalies. Considering a diagnosis of 22q11.2 deletion syndrome, we performed CMA that not only confirmed our diagnosis, but also pointed out an additional de novo 5q21.3q22.2 microdeletion, encompassing APC gene. As a result of the genetic testing we enrolled the patient in a tailored surveillance protocol that enabled the early detection of a hepatoblastoma. The child underwent surgical and chemotherapic treatments with complete cancer eradication.

Conclusions

The concurrent finding of an expected result and an additional deletion of APC gene represents an example of a relevant issue about the health and ethical management of secondary findings revealed by genome-wide tests. Furthermore, this report highlights the need to develop dedicated surveillance guidelines for children with APC-related polyposis and raise the question whether to suspect and screen for APC-related conditions in cases of sporadic hepatoblastomas.
Monitoring circulating dipeptidyl peptidase 3 (DPP3) predicts improvement of organ failure and survival in sepsis: a prospective observational multinational study
Authors:   AdrenOSS-1 Study Investigators, Blet Alice , Deniau Benjamin , Santos Karine , van Lier Dirk P. T. , Azibani Feriel , Wittebole Xavier , Chousterman Benjamin G. , Gayat Etienne , Hartmann Oliver , Struck Joachim , Bergmann Andreas , Antonelli Massimo , Beishuizen Albertus , Constantin Jean-Michel , Damoisel Charles , Deye Nicolas , Di Somma Salvatore , Dugernier Thierry , François Bruno , Gaudry Stephane , Huberlant Vincent , Lascarrou Jean-Baptiste , Marx Gernot , Mercier Emmanuelle , Oueslati Haikel , Pickkers Peter , Sonneville Romain , Legrand Matthieu , Laterre Pierre-François , Mebazaa Alexandre
Published: February 2021

Background

Dipeptidyl peptidase 3 (DPP3) is a cytosolic enzyme involved in the degradation of various cardiovascular and endorphin mediators. High levels of circulating DPP3 (cDPP3) indicate a high risk of organ dysfunction and mortality in cardiogenic shock patients.

Methods

The aim was to assess relationships between cDPP3 during the initial intensive care unit (ICU) stay and short-term outcome in the AdrenOSS-1, a prospective observational multinational study in twenty-four ICU centers in five countries. AdrenOSS-1 included 585 patients admitted to the ICU with severe sepsis or septic shock. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by the Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use and need for renal replacement therapy. cDPP3 levels were measured upon admission and 24 h later.

Results

Median [IQR] cDPP3 concentration upon admission was 26.5 [16.2–40.4] ng/mL. Initial SOFA score was 7 [5–10], and 28-day mortality was 22%. We found marked associations between cDPP3 upon ICU admission and 28-day mortality (unadjusted standardized HR 1.8 [CI 1.6–2.1]; adjusted HR 1.5 [CI 1.3–1.8]) and between cDPP3 levels and change in renal and liver SOFA score (p = 0.0077 and 0.0009, respectively). The higher the initial cDPP3 was, the greater the need for organ support and vasopressors upon admission; the longer the need for vasopressor(s), mechanical ventilation or RRT and the higher the need for fluid load (all p < 0.005). In patients with cDPP3 > 40.4 ng/mL upon admission, a decrease in cDPP3 below 40.4 ng/mL after 24 h was associated with an improvement of organ function at 48 h and better 28-day outcome. By contrast, persistently elevated cDPP3 at 24 h was associated with worsening organ function and high 28-day mortality.

Conclusions

Admission levels and rapid changes in cDPP3 predict outcome during sepsis.

Trial Registration ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015.
Deploying unsupervised clustering analysis to derive clinical phenotypes and risk factors associated with mortality risk in 2022 critically ill patients with COVID-19 in Spain
Authors:   on behalf of COVID-19 SEMICYUC Working Group, Rodríguez Alejandro , Ruiz-Botella Manuel , Martín-Loeches Ignacio , Jimenez Herrera María , Solé-Violan Jordi , Gómez Josep , Bodí María , Trefler Sandra , Papiol Elisabeth , Díaz Emili , Suberviola Borja , Vallverdu Montserrat , Mayor-Vázquez Eric , Albaya Moreno Antonio , Canabal Berlanga Alfonso , Sánchez Miguel , del Valle Ortíz María , Ballesteros Juan Carlos , Martín Iglesias Lorena , Marín-Corral Judith , López Ramos Esther , Hidalgo Valverde Virginia , Vidaur Tello Loreto Vidaur , Sancho Chinesta Susana , Gonzáles de Molina Francisco Javier , Herrero García Sandra , Sena Pérez Carmen Carolina , Pozo Laderas Juan Carlos , Rodríguez García Raquel , Estella Angel , Ferrer Ricard
Published: February 2021

Background

The identification of factors associated with Intensive Care Unit (ICU) mortality and derived clinical phenotypes in COVID-19 patients could help for a more tailored approach to clinical decision-making that improves prognostic outcomes.

Methods

Prospective, multicenter, observational study of critically ill patients with confirmed COVID-19 disease and acute respiratory failure admitted from 63 ICUs in Spain. The objective was to utilize an unsupervised clustering analysis to derive clinical COVID-19 phenotypes and to analyze patient’s factors associated with mortality risk. Patient features including demographics and clinical data at ICU admission were analyzed. Generalized linear models were used to determine ICU morality risk factors. The prognostic models were validated and their performance was measured using accuracy test, sensitivity, specificity and ROC curves.

Results

The database included a total of 2022 patients (mean age 64 [IQR 5–71] years, 1423 (70.4%) male, median APACHE II score (13 [IQR 10–17]) and SOFA score (5 [IQR 3–7]) points. The ICU mortality rate was 32.6%. Of the 3 derived phenotypes, the A (mild) phenotype (537; 26.7%) included older age (< 65 years), fewer abnormal laboratory values and less development of complications, B (moderate) phenotype (623, 30.8%) had similar characteristics of A phenotype but were more likely to present shock. The C (severe) phenotype was the most common (857; 42.5%) and was characterized by the interplay of older age (> 65 years), high severity of illness and a higher likelihood of development shock. Crude ICU mortality was 20.3%, 25% and 45.4% for A, B and C phenotype respectively. The ICU mortality risk factors and model performance differed between whole population and phenotype classifications.

Conclusion

The presented machine learning model identified three clinical phenotypes that significantly correlated with host-response patterns and ICU mortality. Different risk factors across the whole population and clinical phenotypes were observed which may limit the application of a “one-size-fits-all” model in practice.
Identification of MFGE8 and KLK5/7 as mediators of breast tumorigenesis and resistance to COX-2 inhibition
Authors: Tian Jun , Wang Vivian , Wang Ni , Khadang Baharak , Boudreault Julien , Bakdounes Khldoun , Ali Suhad , Lebrun Jean-Jacques
Published: February 2021

Background

Cyclooxygenase 2 (COX-2) promotes stemness in triple negative breast cancer (TNBC), highlighting COX-2 as a promising therapeutic target in these tumors. However, to date, clinical trials using COX-2 inhibitors in breast cancer only showed variable patient responses with no clear significant clinical benefits, suggesting underlying molecular mechanisms contributing to resistance to COX-2 inhibitors.

Methods

By combining in silico analysis of human breast cancer RNA-seq data with interrogation of public patient databases and their associated transcriptomic, genomic, and clinical profiles, we identified COX-2 associated genes whose expression correlate with aggressive TNBC features and resistance to COX-2 inhibitors. We then assessed their individual contributions to TNBC metastasis and resistance to COX-2 inhibitors, using CRISPR gene knockout approaches in both in vitro and in vivo preclinical models of TNBC.

Results

We identified multiple COX-2 associated genes (TPM4, RGS2, LAMC2, SERPINB5, KLK7, MFGE8, KLK5, ID4, RBP1, SLC2A1) that regulate tumor lung colonization in TNBC. Furthermore, we found that silencing MFGE8 and KLK5/7 gene expression in TNBC cells markedly restored sensitivity to COX-2 selective inhibitor both in vitro and in vivo.

Conclusions

Together, our study supports the establishment and use of novel COX-2 inhibitor-based combination therapies as future strategies for TNBC treatment.
Coexistence of the Entner–Doudoroff and Embden–Meyerhof–Parnas pathways enhances glucose consumption of ethanol-producing Corynebacterium glutamicum
Authors: Jojima Toru , Igari Takafumi , Noburyu Ryoji , Watanabe Akira , Suda Masako , Inui Masayuki
Published: February 2021

Background

It is interesting to modify sugar metabolic pathways to improve the productivity of biocatalysts that convert sugars to value-added products. However, this attempt often fails due to the tight control of the sugar metabolic pathways. Recently, activation of the Entner–Doudoroff (ED) pathway in Escherichia coli has been shown to enhance glucose consumption, though the mechanism underlying this phenomenon is poorly understood. In the present study, we investigated the effect of a functional ED pathway in metabolically engineered Corynebacterium glutamicum that metabolizes glucose via the Embden–Meyerhof–Parnas (EMP) pathway to produce ethanol under oxygen deprivation. This study aims to provide further information on metabolic engineering strategies that allow the Entner–Doudoroff and Embden–Meyerhof–Parnas pathways to coexist.

Results

Three genes (zwf, edd, and eda) encoding glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydratase, and 2-keto-3-deoxy-6-phosphogluconate aldolase from Zymomonas mobilis were expressed in a genetically modified strain, C. glutamicum CRZ2e, which produces pyruvate decarboxylase and alcohol dehydrogenase from Z. mobilis. A 13C-labeling experiment using [1-13C] glucose indicated a distinctive 13C distribution of ethanol between the parental and the ED-introduced strains, which suggested an alteration of carbon flux as a consequence of ED pathway introduction. The ED-introduced strain, CRZ2e-ED, consumed glucose 1.5-fold faster than the parental strain. A pfkA deletion mutant of CRZ2e-ED (CRZ2e-EDΔpfkA) was also constructed to evaluate the effects of EMP pathway inactivation, which showed an almost identical rate of glucose consumption compared to that of the parental CRZ2e strain. The introduction of the ED pathway did not alter the intracellular NADH/NAD+ ratio, whereas it resulted in a slight increase in the ATP/ADP ratio. The recombinant strains with simultaneous overexpression of the genes for the EMP and ED pathways exhibited the highest ethanol productivity among all C. glutamicum strains ever constructed.

Conclusions

The increased sugar consumption observed in ED-introduced strains was not a consequence of cofactor balance alterations, but rather the crucial coexistence of two active glycolytic pathways for enhanced glucose consumption. Coexistence of the ED and EMP pathways is a good strategy for improving biocatalyst productivity even when NADPH supply is not a limiting factor for fermentation.
Overexpression of vesicle-associated membrane protein PttVAP27-17 as a tool to improve biomass production and the overall saccharification yields in Populus trees
Authors: Gandla Madhavi Latha , Mähler Niklas , Escamez Sacha , Skotare Tomas , Obudulu Ogonna , Möller Linus , Abreu Ilka N. , Bygdell Joakim , Hertzberg Magnus , Hvidsten Torgeir R. , Moritz Thomas , Wingsle Gunnar , Trygg Johan , Tuominen Hannele , Jönsson Leif J.
Published: February 2021

Background

Bioconversion of wood into bioproducts and biofuels is hindered by the recalcitrance of woody raw material to bioprocesses such as enzymatic saccharification. Targeted modification of the chemical composition of the feedstock can improve saccharification but this gain is often abrogated by concomitant reduction in tree growth.

Results

In this study, we report on transgenic hybrid aspen (Populus tremula×tremuloides) lines that showed potential to increase biomass production both in the greenhouse and after 5 years of growth in the field. The transgenic lines carried an overexpression construct forPopulus tremula×tremuloidesvesicle-associated membrane protein (VAMP)-associated proteinPttVAP27-17that was selected from a gene-mining program for novel regulators of wood formation. Analytical-scale enzymatic saccharification without any pretreatment revealed for all greenhouse-grown transgenic lines, compared to the wild type, a 20–44% increase in the glucose yield per dry weight after enzymatic saccharification, even though it was statistically significant only for one line. The glucose yield after enzymatic saccharification with a prior hydrothermal pretreatment step with sulfuric acid was not increased in the greenhouse-grown transgenic trees on a dry-weight basis, but increased by 26–50% when calculated on a whole biomass basis in comparison to the wild-type control. Tendencies to increased glucose yields by up to 24% were present on a whole tree biomass basis after acidic pretreatment and enzymatic saccharification also in the transgenic trees grown for 5 years on the field when compared to the wild-type control.

Conclusions

The results demonstrate the usefulness of gene-mining programs to identify novel genes with the potential to improve biofuel production in tree biotechnology programs. Furthermore, multi-omic analyses, including transcriptomic, proteomic and metabolomic analyses, performed here provide a toolbox for future studies on the function of VAP27 proteins in plants.
Assessing the sweet sorghum-based ethanol potential on saline–alkali land with DSSAT model and LCA approach
Authors: Fu Jingying , Yan Xiaoxi , Jiang Dong
Published: February 2021

Background

The key problem of non-grain energy plants’ scale development is how to estimate the potential of GHG emission reduction accurately and scientifically. This study presents a method coupled DSSAT (the Decision Support System for Agrotechnology Transfer) and the life cycle assessment (LCA) method to simulate the spatial distribution of sweet sorghum-based ethanol production potential on saline–alkali land. The GHG (greenhouse gas) emission mitigation and net energy gains of the whole life of sweet sorghum-based ethanol production were then analyzed.

Results

The results of the case study in Dongying, Shandong Province, China showed that developing sweet sorghum-based ethanol on saline–alkali land had GHG emission mitigation and energy potentials. The LC-GHG emission mitigation potential of saline–alkali land in Dongying was estimated at 63.9 thousand t CO2 eq, equivalent to the carbon emission of 43.4 Kt gasoline. The LC-NEG potential was predicted at 5.02 PJ, equivalent to the caloric value of 109 Kt gasoline. On average, LC-GHG emission mitigation and LC-NEG were predicted at 55.09 kg CO2 eq/t ethanol and 4.33 MJ/kg ethanol, respectively.

Conclusions

The question of how to evaluate the potential of sweet sorghum-based ethanol development scientifically was solved primarily in this paper. The results will provide an important theoretical support for planning the bioenergy crops on saline–alkali land and develop the fuel ethanol industry.
Risk factors for mortality of diffuse alveolar hemorrhage in systemic lupus erythematosus: a systematic review and meta-analysis
Authors: Jiang Mengdi , Chen Ruxuan , Zhao Lidan , Zhang Xuan
Published: February 2021

Background

Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). The current knowledge of the prognostic factors for SLE-associated DAH is controversial. This meta-analysis was undertaken to investigate the relevant risk factors for mortality in SLE-associated DAH.

Methods

Studies were searched from PubMed, EMBASE, and Web of Science databases published up to May 27, 2020, and were selected or removed according to the inclusion and exclusion criteria. Two reviewers extracted data independently from the enrolled studies, and the odds ratios (OR) or the standardized mean difference (SMD) was utilized to identify and describe the prognostic factors for mortality.

Results

Eight studies encompassing 251 patients with SLE-associated DAH were included in the meta-analysis. No significant publication bias was shown. Age at the diagnosis of DAH (SMD = 0.35, 95% confidence interval (CI) (0.08, 0.61),P = 0.01,I2 = 0.0%) was found to be an independent risk factor of mortality. Longer lupus disease duration (SMD = 0.28, 95% CI (0.01, 0.55),P = 0.042,I2 = 0.0%), concurrent infection (OR = 2.77, 95% CI (1.55, 4.95),P = 0.001,I2 = 37.5%), plasmapheresis treatment (OR = 1.96, 95% CI (1.04, 3.70),P = 0.038,I2 = 14.6%), and mechanical ventilation (OR = 6.11, 95% CI (3.27, 11.39),P < 0.0001,I2 = 23.3%) were also related to poor survival, whereas no noticeable relationships were revealed between survival and concurrent lupus nephritis (OR = 5.45, 95% CI (0.52, 56.95),P = 0.16,I2 = 58.4%) or treatment of cyclophosphamide (CTX) (OR = 0.74, 95% CI (0.16, 3.41),P = 0.70,I2 = 75.5%).

Conclusions

Older age at the diagnosis of DAH, longer disease duration of SLE, concurrent infection, plasmapheresis treatment, and mechanical ventilation were found related to increased mortality in patients with SLE-associated DAH according to our meta-analysis. However, due to limited studies with heterogeneity, these results should be interpreted cautiously. Notably, severe diseases rendered the requirement of plasmapheresis treatment and mechanical ventilation are themselves associated with poor outcome. Randomized trials of therapeutics are needed to determine the most efficacious strategies for SLE-associated DAH for better management of this life-threatening complication.
Bariatric surgery can acutely modulate ER-stress and inflammation on subcutaneous adipose tissue in non-diabetic patients with obesity
Authors: Ferraz-Bannitz Rafael , Welendorf Caroline Rossi , Coelho Priscila Oliveira , Salgado Wilson , Nonino Carla Barbosa , Beraldo Rebeca A. , Foss-Freitas Maria Cristina
Published: February 2021

Background

Bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), is the most effective and durable treatment option for severe obesity. The mechanisms involving adipose tissue may be important to explain the effects of surgery.

Methods

We aimed to identify the genetic signatures of adipose tissue in patients undergoing RYGB. We evaluated 13 obese, non-diabetic patients (mean age 37 years, 100% women, Body mass index (BMI) 42.2 kg/m2) one day before surgery, 3 and 6 months (M) after RYGB.

Results

Analysis of gene expression in adipose tissue collected at surgery compared with samples collected at 3 M and 6 M Post-RYGB showed that interleukins [Interleukin 6, Tumor necrosis factor-α(TNF-α), and Monocyte chemoattractant protein-1(MCP1)] and endoplasmic reticulum stress (ERS) genes [Eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) and Calreticulin (CALR)] decreased during the follow-up (P ≤ 0.01 for all). Otherwise, genes involved in energy homeostasis [Adiponectin and AMP-activated protein kinase (AMPK)], cellular response to oxidative stress [Sirtuin 1, Sirtuin 3, and Nuclear factor erythroid 2-related factor 2 (NRF2)], mitochondrial biogenesis [Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)] and amino acids metabolism [General control nonderepressible 2 (GCN2)] increased from baseline to all other time points evaluated (P ≤ 0.01 for all). Also, expression of Peroxisome proliferator-activated receptor gamma (PPARϒ) (adipogenesis regulation) was significantly decreased after RYGB (P < 0.05). Additionally, we observed that PGC1α, SIRT1 and AMPK strongly correlated to BMI at 3 M (P ≤ 0.01 for all), as well as ADIPOQ and SIRT1 to BMI at 6 M (P ≤ 0.01 for all).

Conclusions

Our findings demonstrate that weight loss is associated with amelioration of inflammation and ERS and increased protection against oxidative stress in adipose tissue. These observations are strongly correlated with a decrease in BMI and essential genes that control cellular energy homeostasis, suggesting an adaptive process on a gene expression level during the caloric restriction and weight loss period after RYGB.

Trial registrationCAAE: 73,585,317.0.0000.5440
Association between ventilatory efficiency, oxygen uptake, and Glittre-ADL test results in patients with chronic heart failure: a preliminary study
Authors: Olímpio Júnior Hebert , Lopes Agnaldo José , Guimarães Fernando Silva , da Cunha Chermont Sergio Luiz Soares Marcos , de Menezes Sara Lúcia Silveira
Published: February 2021

Objective

The Glittre-ADL test (GA-T) is a functional capacity test that stands out for encompassing multiple tasks similar to activities of daily living. As ventilatory efficiency is one of the variables valued in the prognosis of chronic heart failure (CHF), this study aimed to evaluate associations between functional capacity and ventilatory variables in patients with CHF during the GA-T.

Results

Eight patients with CHF and New York Heart Association (NYHA) functional classification II–III underwent the GA-T coupled with metabolic gas analysis to obtain data by means of telemetry. The median total GA-T time was 00:04:39 (00:03:29–00:05:53). Borg dyspnoea scale scores before and after the GA-T were 2 (0–9) and 3 (1–10), respectively (P = 0.011). The relationship between the regression slope relating minute ventilation to carbon dioxide output (VE/VCO2 slope) was correlated with the total GA-T time (rs = 0.714, P = 0.047) and Borg dyspnoea score (rs = 0.761, P = 0.028). The other ventilatory variables showed no significant correlations. Our results suggest that the total GA-T time can be applied to estimate the ventilatory efficiency of patients with CHF. Future studies may use the GA-T in conjunction with other functional capacity tests to guide the treatment plan and evaluate the prognosis.
Clinical characteristics and risk factors for cefaclor-induced immediate hypersensitivity: a retrospective observation at two university hospitals in Korea
Authors: Rhyou Hyo-In , Doo Go-Eun , Yoon Jiwon , Ha Chae-Yeon , Nam Hee-Joo , Woo Sung-Dae , Lee Youngsoo , Nam Young-Hee , Ye Young-Min
Published: February 2021

Background

Cefaclor, a second-generation oral cephalosporin, is widely prescribed to treat infectious diseases. Immediate hypersensitivity (HS) reactions to cefaclor have continuously been reported and are expected to increase with its greater use. This study aimed to investigate the clinical characteristics and risk factors of immediate HS to cefaclor over the most recent 5 years.

Methods

This retrospective study investigated 521 adverse drug reactions (ADRs) to cefaclor at pharmacovigilance centers at two tertiary hospitals from January 2014 to December 2018. In total, 459 patients with immediate HS to cefaclor were reviewed.

Results

A total of 459 cases of cefaclor immediate HS were included among 521 cefaclor ADRs, and anaphylaxis was recorded in 61.2%. Female sex (odds ratio 2.917, 95% confidence interval 2.397–3.550, P < 0.001), age under 65 years (4.225, 3.017–5.916, P < 0.001), hypertension (2.520, 1.875–3.388, P < 0.001), liver diseases (2.189, 1.208–3.967, P = 0.010), asthma (8.075, 5.301–12.302, P < 0.001), and concomitant use of nonsteroidal anti-inflammatory drugs (1.888, 1.554–2.294, P < 0.001) were significantly associated with cefaclor immediate HS.

Conclusions

Cefaclor was found to elicit high proportions of immediate HS and anaphylaxis. Physicians ought to be cautious with prescribing cefaclor to females, individuals with hypertension, liver diseases, or asthma, and patients taking nonsteroidal anti-inflammatory drugs.

Trial registration

This study was retrospectively registered.
Incorporating structural similarity into a scoring function to enhance the prediction of binding affinities
Authors: Ji Beihong , He Xibing , Zhang Yuzhao , Zhai Jingchen , Man Viet Hoang , Liu Shuhan , Wang Junmei
Published: February 2021

In this study, we developed a novel algorithm to improve the screening performance of an arbitrary docking scoring function by recalibrating the docking score of a query compound based on its structure similarity with a set of training compounds, while the extra computational cost is neglectable. Two popular docking methods, Glide and AutoDock Vina were adopted as the original scoring functions to be processed with our new algorithm and similar improvement performance was achieved. Predicted binding affinities were compared against experimental data from ChEMBL and DUD-E databases. 11 representative drug receptors from diverse drug target categories were applied to evaluate the hybrid scoring function. The effects of four different fingerprints (FP2, FP3, FP4, and MACCS) and the four different compound similarity effect (CSE) functions were explored. Encouragingly, the screening performance was significantly improved for all 11 drug targets especially when CSE = S4(S is the Tanimoto structural similarity) and FP2 fingerprint were applied. The average predictive index (PI) values increased from 0.34 to 0.66 and 0.39 to 0.71 for the Glide and AutoDock vina scoring functions, respectively. To evaluate the performance of the calibration algorithm in drug lead identification, we also imposed an upper limit on the structural similarity to mimic the real scenario of screening diverse libraries for which query ligands are general-purpose screening compounds and they are not necessarily structurally similar to reference ligands. Encouragingly, we found our hybrid scoring function still outperformed the original docking scoring function. The hybrid scoring function was further evaluated using external datasets for two systems and we found the PI values increased from 0.24 to 0.46 and 0.14 to 0.42 for A2AR and CFX systems, respectively. In a conclusion, our calibration algorithm can significantly improve the virtual screening performance in both drug lead optimization and identification phases with neglectable computational cost.
Multimodal temporal-clinical note network for mortality prediction
Authors: Yang Haiyang , Kuang Li , Xia FengQiang
Published: February 2021

Background

Mortality prediction is an important task to achieve smart healthcare, especially for the management of intensive care unit. It can provide a reference for doctors to quickly predict the course of disease and customize early intervention programs for the patients in need. With the development of the electronic medical records, deep learning methods are introduced to deal with the prediction task. In the electronic medical records, clinical notes always contain rich and diverse medical information, including the clinical histories and reports during admission. Mortality prediction methods mostly rely on the temporal events such as medical examinations and ignore the related reports and history information in the clinical notes. We hope that we can utilize both temporal events and clinical notes information to get better mortality prediction results.

Results

We propose a multimodal temporal-clinical note network to model both temporal and clinical notes. Specifically, the clinical text are further processed for differentiating the chronic illness patients in the historical information of clinical notes from non-chronic illness patients. In order to further mine the information related to the mortality in the text, we learn the time series embedding with Long Short Term Memory networks and the clinical notes embedding with a label aware convolutional neural network. We also propose a scoring function to measure the importance of clinical note sections. Our approach achieved a better AUCPR and AUCROC than competing methods and visual explanations for word importance showed the interpretability improvement of the model.

Conclusions

We have tested our methodology on the MIMIC-III dataset. Contributions of different clinical note sections were uncovered by visualization methods. Our work demonstrates that the introduction of the medical history related information can improve the performance of the mortality prediction. Using label aware convolutional neural networks can further improve the results.
The control algorithm of whole angle mode for HRG based on the vector composition
Authors: Zhao Wanliang , Cheng Yuxiang , Li Shaoliang , Song Lijun
Published: February 2021

The Hemispherical Resonator Gyroscope (HRG) has many advantages such as high precision, high reliability and long life-time, it is widely used in the space-launcher and the satellites. The HRG has been mechanized to operate in the distinct operating modes, the Force to Rebalanced (FTR) mode and the Whole Angle (WA) mode. In the paper, different from the traditional control algorithm is based on average methods which usually used for the WA mode, a new electrostatic control algorithm is presented, which based on the vector composition and decomposition method to control the equivalent drive force in order to track the phase of the standing wave. The mathematics model and the control algorithm are presented in the paper, and the hardware experimental circuit system is implemented, the HRG has a range of more than 300°/s with the linearity of 40 ppm. Meanwhile, the energy transition efficiency increases by an order of magnitude.
Clusters as institutional entrepreneurs: lessons from Russia
Authors: Lupova-Henry Evgeniya , Blili Sam , Dal Zotto Cinzia
Published: February 2021

In this article, we explore whether organized clusters can act as institutional entrepreneurs to create conditions favorable to innovation in their constituent members. We view self-aware and organized clusters as “context-embedded meta-organizations” which engage in deliberate decision- and strategy-making. As such, clusters are not only shaped by their environments, as “traditional” cluster approaches suggest but can also act upon these. Their ability to act as “change agents” is crucial in countries with high institutional barriers to innovation, such as most transition economies. Focusing on Russia, we conduct two cluster case studies to analyze the strategies these adopt to alter and shape their institutional environments. We find that clusters have a dual role as institutional entrepreneurs. First, these can act collectively to shape their environments due to the power they wield. Second, they can be mechanisms empowering their constituent actors, fostering their reflexivity and creativity, and allowing them to engage in institutional entrepreneurship. Moreover, both collective and individual cluster actors adopt “bricolage” approaches to institutional entrepreneurship to compensate for the lack of resources or institutional frameworks or avoid the pressures of ineffective institutions.
Clubfeet and congenital constriction band syndrome
Authors: Shabani Bujar , Bytyqi Dafina , Bytyqi Cen
Published: February 2021

Background

Clubfeet and constriction band syndrome is a very rare non-idiopathic condition. Treatment is often difficult and the recurrence deformity rate is high. The purpose of this study was to assess the effectiveness of Ponseti method in the treatment of congenital constriction band syndrome accompanied by clubfoot deformity and lymphedema.

Case presentation

We are presenting an interesting case of bilateral clubfeet and congenital circumferential constriction band syndrome in the lower limb. Ponseti method of correcting the congenital clubfoot deformity was applied. Constriction band release is accomplished by two stages completely excising the fibrous band and multiple two-stage Z-plasties on the right calf.

Conclusion

The results of this study indicate that the Ponseti method of gentle, systematic manipulation and weekly cast changes is an effective treatment of non-idiopathic clubfoot distal to congenital amniotic constriction band.
Recommendations for the diagnosis and treatment of paroxysmal kinesigenic dyskinesia: an expert consensus in China
Authors: Cao Li , Huang Xiaojun , Wang Ning , Wu Zhiying , Zhang Cheng , Gu Weihong , Cong Shuyan , Ma Jianhua , Wei Ling , Deng Yanchun , Fang Qi , Niu Qi , Wang Jin , Wang Zhaoxia , Yin You , Tian Jinyong , Tian Shufen , Bi Hongyan , Jiang Hong , Liu Xiaorong , Lü Yang , Sun Meizhen , Wu Jianjun , Xu Erhe , Chen Tao , Chen Tao , Chen Xu , Li Wei , Li Shujian , Li Qinghua , Song Xiaonan , Tang Ying , Yang Ping , Yang Yun , Zhang Min , Zhang Xiong , Zhang Yuhu , Zhang Ruxu , Ouyang Yi , Yu Jintai , Hu Quanzhong , Ke Qing , Yao Yuanrong , Zhao Zhe , Zhao Xiuhe , Zhao Guohua , Liang Furu , Cheng Nan , Han Jianhong , Peng Rong , Chen Shengdi , Tang Beisha
Published: February 2021

Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes. Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology. Clinically, PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action. The major cause of primary PKD is genetic abnormalities, and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance. The proline-rich transmembrane protein 2 (PRRT2) was the first identified causative gene of PKD, accounting for the majority of PKD cases worldwide. An increasing number of studies has revealed the clinical and genetic characteristics, as well as the underlying mechanisms of PKD. By seeking the views of domestic experts, we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD. In this consensus, we review the clinical manifestations, etiology, clinical diagnostic criteria and therapeutic recommendations for PKD, and results of genetic analyses in PKD patients performed in domestic hospitals.
Initial validation of a screening tool for disordered eating in adolescent athletes
Authors: Kennedy Samantha F. , Kovan Jeffrey , Werner Emily , Mancine Ryley , Gusfa Donald , Kleiman Heather
Published: February 2021

Background

Disordered eating (DE) is a growing problem among all athletes, particularly adolescents. To help prevent the progression of DE to a clinical eating disorder (ED), a brief screening tool could offer an efficient method for early identification of DE in athletes and facilitate treatment. The aim of this study is to validate a screening tool for DE that will identify male and female adolescent athletes of all sports and levels of competition who are at risk for DE. The Disordered Eating Screen for Athletes (DESA-6) consists of only 6 items and was designed for use in both male and female athlete populations.

Methods

Validation involved two phases: Phase I consisted of screening high school athletes using the Eating Attitudes Test (EAT-26) and the DESA-6; and Phase II included inviting all high school athletes categorized as “at risk” after screening, plus age- and self-reported gender- matched athletes categorized as not “at risk”, to complete the same surveys a second time along with clinical interview. Validity and regression analyses were used to compare the DESA-6 to the EAT-26 and EDE 17.0D.

Results

When comparing to clinical interview, the DESA-6 had a total sensitivity of 92% and specificity of 85.96%, respectively. Upon comparison of concurrent validity, Phase II DESA-6 had a strong significant positive correlation for both males and females when compared to Phase II EDE 17.0D.

Conclusions

A brief, easy to administer screening tool for recognizing DE that can be used by physicians, psychologists, athletic trainers, registered dietitians, and other sport/healthcare staff is of utmost importance for early intervention, which can lead to improved treatment outcomes. The DESA-6 is a promising tool for risk assessment of DE in athletes.
Anti-Mesothelin CAR T cell therapy for malignant mesothelioma
Authors: Castelletti Laura , Yeo Dannel , van Zandwijk Nico , Rasko John E. J.
Published: February 2021

Malignant mesothelioma (MM) is a treatment-resistant tumor originating in the mesothelial lining of the pleura or the abdominal cavity with very limited treatment options. More effective therapeutic approaches are urgently needed to improve the poor prognosis of MM patients. Chimeric Antigen Receptor (CAR) T cell therapy has emerged as a novel potential treatment for this incurable solid tumor. The tumor-associated antigen mesothelin (MSLN) is an attractive target for cell therapy in MM, as this antigen is expressed at high levels in the diseased pleura or peritoneum in the majority of MM patients and not (or very modestly) present in healthy tissues. Clinical trials using anti-MSLN CAR T cells in MM have shown that this potential therapeutic is relatively safe. However, efficacy remains modest, likely due to the MM tumor microenvironment (TME), which creates strong immunosuppressive conditions and thus reduces anti-MSLN CAR T cell tumor infiltration, efficacy and persistence. Various approaches to overcome these challenges are reviewed here. They include local (intratumoral) delivery of anti-MSLN CAR T cells, improved CAR design and co-stimulation, and measures to avoid T cell exhaustion. Combination therapies with checkpoint inhibitors as well as oncolytic viruses are also discussed. Preclinical studies have confirmed that increased efficacy of anti-MSLN CAR T cells is within reach and offer hope that this form of cellular immunotherapy may soon improve the prognosis of MM patients.
Observing Earth’s magnetic environment with the GRACE-FO mission
Authors: Stolle C. , Michaelis I. , Xiong C. , Rother M. , Usbeck Th. , Yamazaki Y. , Rauberg J. , Styp-Rekowski K.
Published: February 2021

The Gravity Recovery and Climate Experiment Follow-On (GRACE-FO) mission carries magnetometers that are dedicated to enhance the satellite’s navigation. After appropriate calibration and characterisation of artificial magnetic disturbances, these observations are valuable assets to characterise the natural variability of Earth’s magnetic field. We describe the data pre-processing, the calibration, and characterisation strategy against a high-precision magnetic field model applied to the GRACE-FO magnetic data. During times of geomagnetic quiet conditions, the mean residual to the magnetic model is around 1 nT with standard deviations below 10 nT. The mean difference to data of ESA’s Swarm mission, which is dedicated to monitor the Earth’s magnetic field, is mainly within ± 10 nT during conjunctions. The performance of GRACE-FO magnetic data is further discussed on selected scientific examples. During a magnetic storm event in August 2018, GRACE-FO reveals the local time dependence of the magnetospheric ring current signature, which is in good agreement with results from a network of ground magnetic observations. Also, derived field-aligned currents (FACs) are applied to monitor auroral FACs that compare well in amplitude and statistical behaviour for local time, hemisphere, and solar wind conditions to approved earlier findings from other missions including Swarm. On a case event, it is demonstrated that the dual-satellite constellation of GRACE-FO is most suitable to derive the persistence of auroral FACs with scale lengths of 180 km or longer. Due to a relatively larger noise level compared to dedicated magnetic missions, GRACE-FO is especially suitable for high-amplitude event studies. However, GRACE-FO is also sensitive to ionospheric signatures even below the noise level within statistical approaches. The combination with data of dedicated magnetic field missions and other missions carrying non-dedicated magnetometers greatly enhances related scientific perspectives.