bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration of Leaky-Integrate-and-Fire Neurons in Standard Machine Learning Architectures to Generate Hybrid Networks: A Surrogate Gradient Approach
Authors: Gerum Richard C. , Schilling Achim 
Published: July 2021

Abstract
Up to now, modern machine learning (ML) has been based on approximating big data sets with high-dimensional functions, taking advantage of huge computational resources. We show that biologically inspired neuron models such as the leaky-integrate-and-fire (LIF) neuron provide novel and efficient ways of information processing. They can be integrated in machine learning models and are a potential target to improve ML performance. Thus, we have derived simple update rules for LIF units to numerically integrate the differential equations. We apply a surrogate gradient approach to train the LIF units via backpropagation. We demonstrate that tuning the leak term of the LIF neurons can be used to run the neurons in different operating modes, such as simple signal integrators or coincidence detectors. Furthermore, we show that the constant surrogate gradient, in combination with tuning the leak term of the LIF units, can be used to achieve the learning dynamics of more complex surrogate gradients.
To prove the validity of our method, we applied it to established image data sets (the Oxford 102 flower data set, MNIST), implemented various network architectures, used several input data encodings and demonstrated that the method is suitable to achieve state-of-the-art classification performance.
We provide our method as well as further surrogate gradient methods to train spiking neural networks via backpropagation as an open-source KERAS package to make it available to the neuroscience and machine learning community. To increase the interpretability of the underlying effects and thus make a small step toward opening the black box of machine learning, we provide interactive illustrations, with the possibility of systematically monitoring the effects of parameter changes on the learning characteristics.
Contesting the Colonizer or Hopeless Submission? Colonialism, Indigeneity, and Environmental Thinking in India, 1857–1910
Authors: Mandala Vijaya Ramadas 
Published: July 2021

Abstract
This article examines in detail how the forms of national or indigenous consciousness emerged in the sphere of Indian political ecology between 1857 and 1910. The subjects of “ecological indigeneity” and “dispossession” formed as defining characteristics in the articulation of this ecopolitical thinking. The scholarship to date has produced voluminous writings on the political, economic, and social dimension of the histories of colonial unrest, but it has not adequately addressed the issue of how the subtext of environmentalism greatly mattered in shaping some of the resistance movements. Focusing on the period between the 1857 revolt and 1910, this study evaluates three groups – (1) the 1857 Indian rebels and the Gonds; (2) the ādivāsī tribes of Bastar in 1910; and (3) the early Indian Congress Nationalists in the 1880s – to elucidate the emergence of environmentalism and indigenous dispossession in colonial India, which became foundational in critiquing British interventionist policies.
Prenatal serum screening for Down syndrome and neural tube defects in the United States: Changes in utilization patterns from 2012 to 2020
Authors: Lepage Nathalie , Wyatt Philip , Ashwood Edward R , Best Robert G , Long Thomas , Palomaki Glenn E 
Published: July 2021

Objective To compile current usage of serum-based prenatal screening for Down syndrome in the United States and compare it with results from a similar 2011/2012 survey. Setting The College of American Pathologists maternal screening proficiency testing survey includes a supplemental question on the first of three yearly distributions. Methods Information regarding tests offered and the monthly number of pregnancies tested for US-based laboratories were reviewed. Results were stratified by size of laboratory, tests offered, and pregnancies tested. Findings were compared to an earlier survey. Results Fifty-six laboratories reported they will have screened 1,131,336 pregnancies in 2020. Of these, 36% are screened by stand-alone first trimester testing, 48% by stand-alone second trimester testing, and 16% using tests that integrate results from both trimesters. Eighty percent of all serum screens were provided by the five laboratories that performed the most screens (at least 50,000). These five performed similar proportions of first or second trimester screens (42.2% and 41.8%, respectively). Compared to eight years earlier, there are now 54% fewer laboratories. Pregnancies screened using the first trimester, second trimester, and integrated protocols were lower by 27%, 69%, and 72%, respectively. The serum screening activity in the US showed a 62% decrease from 2012 levels. During 2012–2020, the number of cell-free DNA tests increased from negligible to 1,492,332. Conclusions Maternal serum screening for common aneuploidies has changed significantly in eight years with fewer laboratories, a shift toward larger laboratories and a 2.5-fold reduction in pregnancies tested, likely due to the introduction of cell-free DNA screening.
Circular RNA BMI1 Serves as a Potential Target for Diagnosis and Treatment in Esophageal Cancer
Authors: Zhao Qian , Zhu Xin , Ke Jin-ming , Su Xiao-yu , Yi Jing , Wu De-long , Lin Jiang , Deng Zhao-qun 
Published: July 2021

Aims: Previous studies have confirmed that BMI1 is elevated in esophageal cancer, which is a potential therapeutic target for esophageal cancer. However, the clinical significance of circular RNA BMI1 (circ-BMI1) in esophageal cancer is not yet clear. Herein, we revealed the clinical implication of circ-BMI1 in esophageal cancer, and provided a theoretical basis for molecular diagnosis and potential targeted therapy of esophageal cancer. Methods: Firstly, 10 fresh paired esophageal cancer tissues and paracancer tissues, 49 esophageal cancer serum samples and 28 healthy control serum samples were involved in our study. Differential expression and clinical significance of circ-BMI1 in esophageal cancer patients and healthy controls were evaluated by quantitative Real-time RT-PCR (RT-qPCR). Secondly, effects of circ-BMI1 differential expression on biological function of esophageal cancer cell line Eca109 were analyzed. Effects of circ-BMI1 on cell proliferation, migration and colony forming ability were evaluated by CCK-8, wound healing, and colony-forming assay. Cell apoptosis, drug sensitivity tests were also be conducted. Finally, influence of Eca109 cells differentially expressed by circ-BMI1 on tumorigenicity in nude mice was studied. Results: Expression of circ-BMI1 in serum and tissues of esophageal cancer patients was significantly decreased compared to controls ( P < 0.001 and P = 0.003, respectively). Area under the receiver operating characteristic curve (ROC) was 0.726. Cell proliferation, migration and colony forming ability of circBMI1-Eca109 cells were obviously decreased than that of NC-Eca109 cells ( P < 0.05). circBMI1-Eca109 cells were more sensitive to 5-fluorouracil and cisplatin, and tumor volume of nude mice in circBMI1-Eca109 group was smaller ( P < 0.05). Conclusions: The study indicated that expression of circ-BMI1 was significantly down-regulated in esophageal cancer. Overexpression of circ-BMI1 inhibited proliferation, migration, colony formation of Eca109 cells, and tumor growth of Eca109 cells in nude mice. circ-BMI1 may be a potential target for diagnosis and treatment in esophageal cancer.
Perioperative Anomalous Pulmonary Venous Return Evaluation With Low-Dose Cardiac Computed Tomography
Authors: Xiong Li , Patel Mehul D. , Biliciler-Denktas Gurur , Dodge-Khatami Ali , Salazar Jorge , Adebo Dilachew A. 
Published: July 2021

Background: Low-dose multidetector computed tomographic angiography (MDCTA) is playing an increasingly larger role in the diagnosis of anomalous pulmonary venous return (APVR). Despite advances in new computed tomographic (CT) techniques with radiation dose reduction, there are limited studies describing radiation dose parameters to allow routine use of cardiac CT in infants and children with APVR. This study compares cardiac CT findings with intraoperative findings and describes comprehensive radiation exposure parameters. Methods: A retrospective analysis of 27 patients compared MDCTA and intraoperative or cardiac catheterization findings of the pulmonary venous anatomy. Results: A total of 32 MDCTA studies were performed on these 27 patients. Of the 28 studies with subsequent intervention, MDCTA accurately diagnosed the anomalous pulmonary venous anatomy in 27 (96.4%) patients. Narrowing of the pulmonary venous confluence entrance to the coronary sinus was missed on cardiac CT in one patient due to motion artifact, but it was noted intraoperatively. Median estimated effective radiation dose was 0.98 mSv (range: 0.39-3.2 mSv), and mean estimated effective radiation dose was 1.1 ± 0.68 mSv. Median total dose length product (DLP) was 25 mGy cm (range: 10-83 mGy cm), and mean total DLP was 28 ± 18 mGy cm. Median CTDI volume was 3.8 mGy (range: 2.5-14.6 mGy), and mean CTDI volume was 5.0 ± 3.2 mGy. Conclusions: We conclude that modern cardiac MDCTA is the best imaging modality to guide management in both preintervention and postintervention APVR patients. In this study, we describe comprehensive radiation exposure parameters in infants and children with APVR.
Incidence and Recovery of Vocal Fold Immobility Following Pediatric Cardiac Operations
Authors: Barr Jennifer M. , Bowman Kandice , Deshpande Monica , Dewey Elizabeth N. , Milczuk Henry A. , Vo Johnson , Shen Irving , Muralidaran Ashok 
Published: July 2021

Background: Loss of laryngeal function after congenital cardiac surgery causes morbidity and prolongs hospitalization. Early diagnosis of vocal fold immobility (VFI) and referral to pediatric otolaryngology (pOTO) aids in laryngeal rehabilitation. Understanding the incidence and recovery rates of VFI enables counseling for families of infants undergoing high-risk surgery. Methods: A retrospective chart review from November 2014 to July 2019 of infants postcardiac surgery where the aortic arch or surrounding structures were manipulated and were screened via flexible fiberoptic laryngoscopy (FFL) at a single institution was performed. Patients were divided into five surgical categories: Norwood procedure, aortic arch augmentation via median sternotomy, arterial switch operation, coarctation repair via lateral thoracotomy, and cardiac surgeries including ligation of a patent ductus arteriosus (PDA). Patients undergoing isolated PDA ligation were excluded. Results: One hundred ninety-nine qualifying operations occurred during this period; 28 patients did not undergo FFL before discharge and were excluded from the analysis. Immediately following cardiac surgery, 34% (58 of 171 patients) had VFI. Follow-up was completed by 38 of 58 patients with VFI. Complete recovery was demonstrated in 63% (24 of 38) of patients by 6 months and in 86% (33 of 38) within 18 months. The highest risk occurred with the Norwood procedure and arch augmentation via median sternotomy. Conclusions: Infants undergoing surgery involving the aortic arch and surrounding structures have high rates of VFI. Follow-up by pOTO is recommended to optimize laryngeal rehabilitation. Most patients have spontaneous recovery within 18 months of cardiac surgery.
BTK inhibition sensitizes acute lymphoblastic leukemia to asparaginase by suppressing the amino acid response pathway
Authors: Butler Miriam , van Ingen Schenau Dorette S. , Yu Jiangyan , Jenni Silvia , Dobay Maria P. , Hagelaar Rico , Vervoort Britt M. T. , Tee Trisha M. , Hoff Fieke W. , Meijerink Jules P. , Kornblau Steven M. , Bornhauser Beat , Bourquin Jean-Pierre , Kuiper Roland P. , van der Meer Laurens T. , van Leeuwen Frank N. 
Published: July 2021

Abstract
Asparaginase (ASNase) therapy has been a mainstay of acute lymphoblastic leukemia (ALL) protocols for decades and shows promise in the treatment of a variety of other cancers. To improve the efficacy of ASNase treatment, we used a CRISPR/Cas9-based screen to identify actionable signaling intermediates that improve the response to ASNase. Both genetic inactivation of Bruton’s tyrosine kinase (BTK) and pharmacological inhibition by the BTK inhibitor ibrutinib strongly synergize with ASNase by inhibiting the amino acid response pathway, a mechanism involving c-Myc–mediated suppression of GCN2 activity. This synthetic lethal interaction was observed in 90% of patient-derived xenografts, regardless of the genomic subtype. Moreover, ibrutinib substantially improved ASNase treatment response in a murine PDX model. Hence, ibrutinib may be used to enhance the clinical efficacy of ASNase in ALL. This trial was registered at www.clinicaltrials.gov as # NCT02884453.
Transcriptomic changes in peripheral blood mononuclear cells with weight loss: systematic literature review and primary data synthesis
Authors: Day Kaitlin , Dordevic Aimee L. , Truby Helen , Southey Melissa C. , Coort Susan , Murgia Chiara 
Published: July 2021

Abstract
Background and objectives
Peripheral blood mononuclear cells (PBMCs) have shown promise as a tissue sensitive to subtle and possibly systemic transcriptomic changes, and as such may be useful in identifying responses to weight loss interventions. The primary aim was to comprehensively evaluate the transcriptomic changes that may occur during weight loss and to determine if there is a consistent response across intervention types in human populations of all ages.

Methods
Included studies were randomised control trials or cohort studies that administered an intervention primarily designed to decrease weight in any overweight or obese human population. A systematic search of the literature was conducted to obtain studies and gene expression databases were interrogated to locate corresponding transcriptomic datasets. Datasets were normalised using the ArrayAnalysis online tool and differential gene expression was determined using the limma package in R. Over-represented pathways were explored using the PathVisio software. Heatmaps and hierarchical clustering were utilised to visualise gene expression.

Results
Seven papers met the inclusion criteria, five of which had raw gene expression data available. Of these, three could be grouped into high responders (HR, ≥ 5% body weight loss) and low responders (LR). No genes were consistently differentially expressed between high and low responders across studies. Adolescents had the largest transcriptomic response to weight loss followed by adults who underwent bariatric surgery. Seven pathways were altered in two out of four studies following the intervention and the pathway ‘cytoplasmic ribosomal proteins’ (WikiPathways: WP477) was altered between HR and LR at baseline in the two datasets with both groups. Pathways related to ‘toll-like receptor signalling’ were altered in HR response to the weight loss intervention in two out of three datasets.

Conclusions
Transcriptomic changes in PBMCs do occur in response to weight change. Transparent and standardised data reporting is needed to realise the potential of transcriptomics for investigating phenotypic features.

Registration number
PROSPERO: CRD42019106582
Transcriptomic analyses of cacao flavonoids produced in photobioreactors
Authors: Gallego Adriana M. , Rojas Luisa F. , Valencia Wilmar G. , Atehortúa Lucía , Urrea Aura I. , Fister Andrew S. , Guiltinan Mark J. , Maximova Siela N. , Pabón-Mora Natalia 
Published: July 2021

Abstract
Background
Theobroma cacao is a major source of flavonoids such as catechins and their monomers proanthocyanidins (PAs), widely studied for their potential benefits in cardiovascular diseases. Light has been shown to promote plant secondary metabolite production in vitro. In this study, cacao cells cultured in 7.5 L stirred tank photobioreactors (STPs) were exposed to a change of white to blue LED lights for 28 days (d).

Results
Transcriptomic analyses were performed in three time points comparing changing expression patterns, after cell exposure to white light (d0-VS-d14), after a shift from white to blue light (d14-VS-d15), and after an extended period of blue light for the following 15 days (d15-VS-d28). Under white light, there was enrichment in metabolic pathways associated with cell growth (carbon, glycolysis, and amino acid biosynthesis) accompanied by a significant increase in the PAs content. In the shift to blue light, further increase in PAs content was observed concomitantly with the significant expression of TWO-COMPONENT RESPONSE REGULATOR genes involved in the early stress responses via circadian clock and hormone pathways. Under blue light exposure, we observed a depletion of PAs content associated with ROS-mediated stress pathways.

Conclusions
Light effects on large-scale cell cultures in photobioreactors are complex and pleiotropic; however, we have been able to identify key regulatory players upstream cacao flavonoid biosynthesis in STPs, including TWO-COMPONENT SYSTEM and ROS-signaling genes. The crosstalk between flavonoid biosynthesis and regulatory networks led to understand the dynamics of flavonoid production and degradation in response to light-driven ROS signals. This can be used to optimize the time, and the yield of in vitro targeted metabolites in large-scale culture systems.
Analyzing the gonadal transcriptome of the frog Hoplobatrachus rugulosus to identify genes involved in sex development
Authors: Tang Yun , Chen Jing-Yi , Ding Guo-Hua , Lin Zhi-Hua 
Published: July 2021

Abstract
Background
The tiger frog (Hoplobatrachus rugulosus) is listed as a national Class II protected species in China. In the context of global warming, the sex ratio of amphibians will be affected, and the development of the population will be limited. Therefore, considering the potential for a decrease in the number of amphibians, studying sex evolution and molecular regulation of gonadal development in H. rugulosus, phenomenon that are currently unclear, is of great significance.

Results
Here, H. rugulosus was used to explore the mechanisms regulating gonadal development in amphibians. Illumina HiSeq 3000 was used to sequence the gonadal transcriptome of male and female H. rugulosus at two growth stages to identify genes related to gonadal development and analyze expression differences in the gonads. This analysis indicated that cyp17α, hsd3β, hsd11β1, cyp19α, and hsd17β12 perform vital functions in sex development in amphibians. Specifically, the expression of cyp3α, cyp17α, hsd3β, hsd11β1, sox2, sox9, sox30, soat, cyp19α, hsd17β12, and hspα1s was correlated with gonadal development and differentiation in H. rugulosus, as determined using the quantitative reverse transcriptase-polymerase chain reaction.

Conclusion
Significant differences were found in the gonadal gene expression levels in H. rugulosus of both sexes, and we identified a steroid hormone synthesis pathway in this species and analyzed related gene expression, but the changes during sex differentiation were still unclear. To our knowledge, this report presents the first analysis of the H. rugulosus gonadal transcriptome and lays the foundation for future research.
Colorectal cancer treatment using bacteria: focus on molecular mechanisms
Authors: Ebrahimzadeh Sara , Ahangari Hossein , Soleimanian Alireza , Hosseini Kamran , Ebrahimi Vida , Ghasemnejad Tohid , Soofiyani Saiedeh Razi , Tarhriz Vahideh , Eyvazi Shirin 
Published: July 2021

Abstract
Background
Colorectal cancer which is related to genetic and environmental risk factors, is among the most prevalent life-threatening cancers. Although several pathogenic bacteria are associated with colorectal cancer etiology, some others are considered as highly selective therapeutic agents in colorectal cancer. Nowadays, researchers are concentrating on bacteriotherapy as a novel effective therapeutic method with fewer or no side effects to pay the way of cancer therapy. The introduction of advanced and successful strategies in bacterial colorectal cancer therapy could be useful to identify new promising treatment strategies for colorectal cancer patients.

Main text
In this article, we scrutinized the beneficial effects of bacterial therapy in colorectal cancer amelioration focusing on different strategies to use a complete bacterial cell or bacterial-related biotherapeutics including toxins, bacteriocins, and other bacterial peptides and proteins. In addition, the utilization of bacteria as carriers for gene delivery or other known active ingredients in colorectal cancer therapy are reviewed and ultimately, the molecular mechanisms targeted by the bacterial treatment in the colorectal cancer tumors are detailed.

Conclusions
Application of the bacterial instrument in cancer treatment is on its way through becoming a promising method of colorectal cancer targeted therapy with numerous successful studies and may someday be a practical strategy for cancer treatment, particularly colorectal cancer.
The core autophagy machinery is not required for chloroplast singlet oxygen-mediated cell death in the Arabidopsis thaliana plastid ferrochelatase two mutant
Authors: Lemke Matthew D. , Fisher Karen E. , Kozlowska Marta A. , Tano David W. , Woodson Jesse D. 
Published: July 2021

Abstract
Background
Chloroplasts respond to stress and changes in the environment by producing reactive oxygen species (ROS) that have specific signaling abilities. The ROS singlet oxygen (1O2) is unique in that it can signal to initiate cellular degradation including the selective degradation of damaged chloroplasts. This chloroplast quality control pathway can be monitored in the Arabidopsisthaliana mutant plastid ferrochelatase two (fc2) that conditionally accumulates chloroplast 1O2 under diurnal light cycling conditions leading to rapid chloroplast degradation and eventual cell death. The cellular machinery involved in such degradation, however, remains unknown. Recently, it was demonstrated that whole damaged chloroplasts can be transported to the central vacuole via a process requiring autophagosomes and core components of the autophagy machinery. The relationship between this process, referred to as chlorophagy, and the degradation of 1O2-stressed chloroplasts and cells has remained unexplored.

Results
To further understand 1O2-induced cellular degradation and determine what role autophagy may play, the expression of autophagy-related genes was monitored in 1O2-stressed fc2 seedlings and found to be induced. Although autophagosomes were present in fc2 cells, they did not associate with chloroplasts during 1O2 stress. Mutations affecting the core autophagy machinery (atg5, atg7, and atg10) were unable to suppress 1O2-induced cell death or chloroplast protrusion into the central vacuole, suggesting autophagosome formation is dispensable for such 1O2–mediated cellular degradation. However, both atg5 and atg7 led to specific defects in chloroplast ultrastructure and photosynthetic efficiencies, suggesting core autophagy machinery is involved in protecting chloroplasts from photo-oxidative damage. Finally, genes predicted to be involved in microautophagy were shown to be induced in stressed fc2 seedlings, indicating a possible role for an alternate form of autophagy in the dismantling of 1O2-damaged chloroplasts.

Conclusions
Our results support the hypothesis that 1O2-dependent cell death is independent from autophagosome formation, canonical autophagy, and chlorophagy. Furthermore, autophagosome-independent microautophagy may be involved in degrading 1O2-damaged chloroplasts. At the same time, canonical autophagy may still play a role in protecting chloroplasts from 1O2-induced photo-oxidative stress. Together, this suggests chloroplast function and degradation is a complex process utilizing multiple autophagy and degradation machineries, possibly depending on the type of stress or damage incurred.