bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the mechanisms of action and mosquito larva midgut response to a yeast- encapsulated orange oil larvicide
Authors: Kelly Patrick H. , Yingling Alexandra V. , Ahmed Anwar , Hurwitz Ivy , Ramalho-Ortigao Marcelo 
Published: February 2022

Abstract
Here, we assessed the mechanism of action of a yeast-encapsulated orange essential oil (YEOO) larvicide. YEOO is readily ingested by mosquito larvae leading to midgut epithelial cell responses associated changes in gene expression profiles and severe epithelial damage that were detected shortly after YEOO ingestion. In Aedes aegypti 3rd instar larvae exposed to YEOO at LC90, greater than 10 fold induction of the effector caspase CASPS8, >11 fold induction of the midgut epithelial regenerator Vein, and >26 fold induction of the inhibitor of apoptosis gene IAP1 compared to control larvae by 8 h after YEOO ingestion. For sublethal concentrations (<LC50), we observed significant differential expression of the cytochrome P450 detoxification enzyme families CYP6 and CYP9. Midgut epithelial damage was highlighted by destruction of microvilli, vacuolization of midgut cells, damage to cell junctions and basal lamina as early as 30 min. Curiously, the larval type 2 peritrophic matrix (PM2) structural integrity and porosity appeared to remain unchanged, suggestive that the orange oil released from the digested YEOO capsules seep through the PM2. Of relevance, our results strongly suggest that YEOO effective killing is due to a generalized broad-acting mechanism combining unregulated epithelial damage and apoptosis, with concomitant expression of multiple innate response genes involved in epithelial regeneration and detoxification. YEOO’s amenability for use as part of an integrated vector management makes this novel larvicide a practical approach for mosquito larval control in the future.
Simulation of the Third Wave of COVID 19 Infections in Zambia using the SIR Model
Authors: Mwale Moses , Kanjere Boniface , Kanchele Chuncky , Mukosa Solomon 
Published: February 2022

Abstract
Background
Various mathematical modeling approaches are used to provide a robust framework for understanding the transmission dynamics of infectious diseases in human populations. In an epidemic, models can be used for the analysis of the spread of a disease, forecasting, identifying trends and making parameter estimates which can be used for planning and implementing intervention measures.
Methods
This study utilizes the classical Susceptible - Infected - Recovered (SIR) model to analyze the evolution of COVID-19 in Zambia during the third wave of infections. The model is fitted to actual COVID-19 data for Zambia for the third wave of the pandemic obtained from the Zambia National Public Health Institute (ZNPHI). The transmission and recovery rates are estimated by minimizing the error between the fitted curve and the real data using the least square approach.
Results
Model simulations indicate that the basic reproductive number (\({R}_{0}\)) for Zambia is 1.31 meaning that, on average, 1.31 persons are infected for each infected person. At the worst point of the epidemic, we expect that 591,743 people will contract the virus and 7,144 fatalities will be recorded. To prevent the spread of infection, the model estimates that at least 24 percent of the population will need to be vaccinated. With the country's projected population of about 18.91 million, this translates to roughly 4.5 million people.
Conclusion
The severity of COVID-19 infection, hospitalizations, and deaths in Zambia is substantially higher than national testing data suggests, according to model projections. More modeling work is needed to acquire accurate estimates of the disease burden in society, to inform resource allocation, and to aid mitigation planning, especially in countries that may lack adequate national surveillance systems.
Hypomethylation Of The Hepc Genome In High D-Glucose Concentrations: Initiation Of Angiogenic Failure?
Authors: Fernández-Garcés Paulina , Hinojosa-Moreno Marcela , Gallegos Soraya Gutierrez 
Published: February 2022

Abstract
Background: Accumulating evidence suggests that Diabetes mellitus type 2 affects the angiogenic functions of Endothelial Progenitor Cells and a good glycemic control is not enough to restore these functions. Therefore, it is necessary to investigate if there are changes at the epigenetic level that can explain this phenomenon. Results: We isolated EPC from mononuclear cells and cultured them in 5 mM of D-glucose equivalent to normal glycemia, 10 mM equivalent to a glycemia clinically acceptable for a diabetic patient, and 20 mM of D-glucose corresponding to a value of glycemia in a patient with poor glycemic control; and we evaluated the adhesion capacity of EPC to fibronectin matrix. We also determined global methylation levels by slot blot for the 5-methylcytocine and 5-hydroxymethylcytocine and the expression levels of the TET1 and TET2 genes using qPCR. We found that high glucose concentrations do not affect EPC differentiation. Cells grown at 10 mM D-glucose do not decrease their adhesion to fibronectin matrix but at 20 mM culture we observed decrease in their adhesion (p> 0.05), but interesting, in both culture conditions we observed hypomethylation of the genome (p> 0.05) accompanied with an increase in 5-hydroxymethylcytocine in cells treated with 20mM D-glucose (p <0.05). We did not observe statistically significant changes in the mRNA levels of the TET1 and TET2 genes. Treatment with demethylating agent 5-aza-2'-deoxycytidine, shows that adhesion failure is dependent on genome demethylation (p> 0.001).Conclusions: High concentrations of D-glucose (20mM) generate an active hypomethylation of the hEPC genome and a decrease in their adhesion capacity. Although the concentration of D-Glucose considered as "clinically acceptable" glycemia in a diabetic patient (10mM), do not produce significant changes in hEPC adhesion to fibronectin matrix, a global hypomethylation of the genome, was observed, which could be responsible for impair angiogenic functions of the hEPC in patients with good glycemic control.
Hetero-interpenetrated metal-organic frameworks
Authors: Perl David , Lee Seok , Ferguson Alan , Jameson Geoffrey , Telfer Shane 
Published: February 2022

Abstract
Interpenetrated metal-organic frameworks (MOFs) comprise two or more lattices that are mutually entangled. Interpenetration tunes the structures and pore architectures of MOFs to influence their interactions with guest molecules. Typically, the interpenetrating sublattices are identical. Hetero-interpenetrated MOFs, in contrast, have sublattices that are different to one another. While they can be produced by serendipity, to develop a deliberate strategy for making hetero-interpenetrated MOFs we employed the cubic 𝛂-MUF-9 framework as a host sublattice. 𝛂-MUF-9 is able to template the secondary growth of a second, interpenetrating, sublattice in its pores to produce hetero-interpenetrated MOFs. In certain cases, the sublattices cannot be produced via standalone reactions and are observed here for the first time. Unique functional properties are enabled by hetero-interpenetrated MOFs such as asymmetric catalysis. We grew a catalytically-active sublattice inside 𝛂-MUF-10, a chiral host. The chiral pore environment of the host imparts asymmetry on the catalytic activity of interpenetrating sublattice to give reaction products with an enantiomeric excess. This deliberate strategy for synthesizing hetero-interpenetrated MOFs opens new perspectives on framework structures and pore environments and allows unprecedented functional properties to emerge.
Shouting strengthens voluntary force during sustained maximal effort through enhancement of motor system state via motor commands
Authors: Takarada Yudai , Nozaki Daichi 
Published: February 2022

Abstract
Previous research indicates that producing a shout during momentary maximal exertion effort enhances the force levels of maximal voluntary contraction through the enhancement of motor cortical excitability. However, the muscular force-enhancing effects of shouting on sustained maximal force production remain unclear. We instigated the effect of shouting on the motor system state by examining motor evoked potentials in response to transcranial magnetic stimulation applied over the contralateral primary motor cortex (M1) during sustained maximal voluntary contraction, and by evaluating handgrip maximal voluntary force. Analysis revealed that producing a shout significantly increased handgrip maximal voluntary force and reduced the silent period. Our results indicate that producing a shout increased handgrip voluntary force during sustained maximal exertion effort through the reduced silent period. This study provides evidence that the muscular force-enhancing effect of shouting during maximal force exertion is related to the enhancement of motor system activity caused by the additional drive of shouting operating on the motor system (i.e., shouting-induced excitatory input to M1).
Optogenetic control of mGluR1 signaling modulates synaptic plasticity and cerebellum driven learning
Authors: Surdin Tatjana , Grömmke Michelle , Böke Hanna , Barcik Maike , Azimi Zohre , Jancke Dirk , Herlitze Stefan , Mark Melanie , Siveke Ida 
Published: February 2022

Abstract
Neuronal plasticity underlying cerebellar learning behavior is strongly associated with type 1 metabotropic glutamate receptor (mGluR1) signaling. This receptor is located at perisynaptic sites at cerebellar Purkinje cells (PCs) and detects glutamate spill over. Activation of mGluR1 leads to activation of the Gq/11 pathway, inducing synaptic plasticity at the parallel fiber-Purkinje cell synapse (PF-PC) in form of long-term depression (LTD). To optogenetically modulate mGluR1 signaling we fused mouse melanopsin (OPN4) that activates the Gq/11 pathway to the C-termini of mGluR1 splice variants (OPN4-mGluR1a and OPN4-mGluR1b). We provide the prove-of-concept approach to modulate synaptic plasticity via optogenetic activation of OPN4-mGluR1a inducing LTD at the PF-PC synapse in vitro. Moreover, we demonstrate that light activation of mGluR1a signaling pathway by OPN4-mGluR1a in PCs leads to an increase in intrinsic activity of PCs in vivo and improved cerebellum driven learning behavior.
Structural Design of Supreme Controller with Uncontrollable Transitions
Authors: Mohaman Gonza , ALLA Hassane , BITJOKA Laurent 
Published: February 2022

Abstract
In the framework of Petri net (PN), the structural supervisory control of discrete event system (DES) is an exciting method to design controller in the presence of uncontrollable transitions. Especially, this method addresses the controllability problem existing in the desired functioning PN. The controllability condition defined by uncontrollable synchronization can be expressed as constraints (GMEC). This leads to design place invariant-based controller, implemented through control places connected to plant transitions. The controller is maximally permissive if the transitions are controllable. Implying that the controller insures that the constraints are never violated directly or may be violated through the firing of uncontrollable transitions. But, if one control place is connected to uncontrollable transition, then the controller is non-admissible, since it cannot prevent such transition. The common idea is to transform the constraints or to displace the controller arcs. Unfortunately, the constraints transformation is computationally complex and not structural, while the arcs displacement approach is unsystematic. Our idea consists to iterate the structural supervisory control method to ensure a systematic displacement of controller arcs, so that no control place is input place of uncontrollable transition. This approach focuses on structural design of a less restrictive and admissible controller, namely the supreme controller.
Trp53 and Rb1 deficiency in chondrocytes spontaneously develop chondrosarcoma by activation of YAP signaling
Authors: Li Yang , Yang Shuting , Liu Yang , Yang Shuying 
Published: February 2022

Abstract
Chondrosarcoma (CHS) is a rare type of soft sarcoma with increased production of cartilage matrix arising from soft bone tissues. Currently, surgical resection is the primary clinical treatment for chondrosarcoma due to the poor response to radiotherapy and chemotherapy. However, the therapeutic effect is not satisfactory due to the higher local recurrence rate. Thus, management and elucidation of the pathological mechanism of chondrosarcoma remain an ongoing challenge, and development of effective chondrosarcoma mouse models and treatment options are urgently needed. Here, we generated a new transgenic chondrosarcoma model by double conditional deletions of Trp53 and Rb1 in chondrocyte lineage which spontaneously caused spinal chondrosarcoma and lung metastasis. Bioinformatic analysis of human soft sarcoma database showed that Trp53 and Rb1 genes had higher mutations, reaching up to approximately 33.5% and 8.7%, respectively. Additionally, Trp53 and Rb1 signatures were decreased in the human and mouse chondrosarcoma tissues. Mechanistically, we found that YAP expression and activity were significantly increased in mouse Col2-Cre;Trp53f/f/Rb1f/f chondrosarcoma tissues compared to the adjacent normal cartilage. Knockdown of YAP in primary chondrosarcoma cells significantly inhibited chondrosarcoma proliferation, invasion, and tumorsphere formation. Chondrocyte lineage ablation of YAP delayed chondrosarcoma progression and lung metastasis in Col2-Cre;Trp53f/f/Rb1f/f mice. Moreover, we found that metformin served as a YAP inhibitor, which bound to the activity area of YAP protein, and inhibited chondrosarcoma cell proliferation, migration, invasion, and progression in vitro and significantly suppressed chondrosarcoma formation in vivo. Collectively, this study identifies the inhibition of YAP may be effective therapeutic strategies for treatment of chondrosarcoma.
New, Minimally Approach for Middle and Distal Third Humeral Shaft Fractures a Cadaveric Study and Clinical Case Series
Authors: Liu Tang , Yang Jing , Li Hua , Yang Zhenxing , Wang Jian , Maimaitiaili Abuduheilili , Lu Zhanxin , Tao Cheng 
Published: February 2022

Abstract
Purpose Fractures of the humeral shaft, especially the treatment of extraarticular fractures of the distal third of the humerus, which is a challenge. We hypothesize that a new feasibility and safety minimally invasive surgical approach can be used for the treatment of middle-and distal-third humeral fractures. The main purpose of this study was to evaluate this new approach and develop it.Methods In 13 adult cadaver arms, a minimally invasive surgical approach to the anteromedial humerus was simulated, followed by fixation with a locking compression plate and the measurement of several sets of anatomical data to clarify the possible risk of iatrogenic vascular and nerve injury in this surgical approach. Between 2017 and 2019 in 18 patients with humeral fractures who were treated with this surgical approach.Results Patients were followed for average 20.1 months (range, 15 – 34 months). The distance from the vertex of the medial epicondyle to the median nerve was 2.96 cm (range, 2.30 – 3.40 cm). The distance from the tip of the distal end of the screw in the medial epicondyle to the ulnar nerve was 1.7 mm (range, 0.00 – 4.00 mm). The shortest distance between the Olecranon Fossa and the tip of the screws at the distal end of the plate in the medial humeral epicondyle was 0.69 mm (range, 0.00 – 7.00 mm). The distance from the vertex of the epicondyle to the intersection of the median nerve and the distal end of the underlying steel plate was 6.28 cm (range, 5.70 – 6.90 cm).Conclusions This approach does not cause iatrogenic neurovascular injury and provides sufficient strength for the fixation of fractures of the middle and distal thirds of the humerus. This approach can be used as an alternative in the treatment of extraarticular fractures of the middle and distal thirds of the humerus.Type of study/level of evidence Therapeutic Level IV.
Interpretable Machine Learning Prediction of All-Cause Mortality
Authors: Qiu Wei , Chen Hugh , Dincer Ayse , Lundberg Scott , Kaeberlein Matt R. , Lee Su-In 
Published: February 2022

Abstract
Background Unlike linear models, complex machine learning models can capture non-linear interrelations and provide opportunities to identify novel risk factors. Explainable artificial intelligence can improve prediction accuracy and reveal unprecedented insights into outcomes like mortality. This paper comprehensively analyzes all-cause mortality by explaining complex machine learning models. Methods We propose the IMPACT framework that uses a principled XAI technique to explain a state-of-the-art tree ensemble mortality prediction model. We apply IMPACT to understand all-cause mortality for 1-, 3-, 5-, and 10-year follow-up times and age groups of <40, 40-65, 65-80, and <=80 years old within the NHANES 1999-2014 dataset, which contains 47,261 samples and 151 features. Results Here we show that IMPACT models achieve high accuracy in every mortality prediction task. Using IMPACT, we identify several overlooked risk factors and interactions. Furthermore, we identify relationships between laboratory features and mortality that may suggest adjusting established reference intervals. Finally, we develop highly accurate, efficient, and interpretable mortality risk scores. We ensure generalizability by performing temporal validation of the mortality risk scores and external validation of the key findings with the UK Biobank dataset. All our results and risk scores are available on a website where the relationships can be explored in detail to generate new research hypotheses. Conclusions IMPACT’s unique strength is the explainable prediction, which provides insights into the complex, non-linear relationships between mortality and individual's features. Our explainable risk scores could help individuals improve self-awareness of their health status and help clinicians identify patients with high risk. IMPACT takes a significant step towards bringing contemporary developments in XAI, which have already revolutionized fields like finance, to epidemiological research.
The infiltration pattern of microenvironmental cells and different immune escape mechanisms in colorectal cancer
Authors: Mao Yihao , Feng Qingyang , Chang Wenju , Lv Yang , Xu Yuqiu , Chang Jiang , Zheng Peng , Yu Shanchao , Zhang Zhiyuan , Li Zhiqiang , Lin Qi , Tang Wentao , Zhu Dexiang , Ji Meiling , Ren Li , Wei Ye , He Guodong , Xu Jianmin 
Published: February 2022

Abstract
Background: The tumour microenvironment (TME) plays a crucial role in tumour progression and metastasis. However, the infiltration pattern of TME cells in CRC samples and the immune escape mechanism underneath have not been studied sufficiently.Methods: Transcriptomic data from public datasets were retrieved online. In total, 1802 samples from the microarray dataset and 619 samples from the TCGA dataset were enrolled. The ssGSEA algorithm and unsupervised clustering were used for TME cells infiltration speculation and infiltration pattern recognition. Results: CRC samples can be classified into three distinct TME cell subtypes. Subtype 1, the immune-active subtype, was characterised by high infiltration of activated adaptive immune cells. Subtype 2, the immune-desert subtype, featured high tumour purity and low infiltration of immune and stromal cells. And subtype 3, stroma-rich subtype, had high infiltration of stromal cells. The stroma-rich subtype conferred a significantly worse prognosis. Three subtypes had different immune escape mechanisms. The immune-active subtype has the highest immune checkpoint expression level. In comparison, the immune-desert subtype had the lowest immunogenicity and the defective antigen presentation. And the stroma-rich subtype lacked activated immune cells.Conclusions: Distinct TME cell subtypes and immune escape mechanisms may provide inspiration and direction for further researches on CRC immunotherapy.
Feasibility of Robotic Surgery in Comparison to the conventional Laparoscopic and Open Procedures in Urology: A Systematic Review
Authors: Zahid Afra , Ayyan Muhammad , Farooq Minaam , Cheema Huzaifa Ahmad , Shahid Abia , Naeem Faiza , Ilyas Muhammad Abdullah , Sohail Shehreen 
Published: February 2022

Abstract
PURPOSE
To establish the feasibility of robotic surgical procedures in urology in terms of the applications, pros and cons as well as the postoperative and oncological outcomes while comparing it with the conventional approaches.
METHODS
A systematic search of electronic databases was performed to identify Randomized Controlled Trials and Cohort studies on Robot Assisted urological surgical procedures in comparison with the conventional methods. The quality assessment of included studies was performed using the Newcastle-‎Ottawa Scale and the revised Cochrane “Risk of Bias” tool. A qualitative narrative synthesis of the data extracted from the studies was performed and presented in tabulated form.
RESULTS
After screening, 34 studies were included in our review (3 Randomized Controlled Trials and 31 Cohort studies). Robot Assisted Prostatectomy appears to be associated with lower estimated blood loss and shorter length of hospital stay. For Robot Assisted Cystectomy, the results suggest longer operative time and fewer complications. Robot Assisted Radical Nephrectomy was found to be associated with fewer perioperative complications and longer mean operative time while Robot Assisted Partial Nephrectomy was associated with less positive surgical margins, no recurrence and reduced need of postoperative analgesia. The mean operative time was longer while length of stay was shorter for the robotic approach in inguinal lymphadenectomy and ureteral re-implantation.
CONCLUSION
The feasibility of Robot Assisted surgery varied for different outcome measures as well as for different procedures. Some common advantages were shorter length of stay, lesser blood loss and fewer complications while the drawbacks included longer operative time.
Is the Western Himalayan region vulnerable in respect to downscaled precipitation?
Authors: Meher Jitendra Kumar , Das Lalu 
Published: February 2022

Abstract
Statistical downscaling is the technique of linking large-scale predictors and local scale predictand through a relationship that is assumed to be useful to generate local scale climate change information from GCMs driven large-scale future projection. An attempt has been made to construct downscaled seasonal and annual rainfall change scenarios over different station locations of the Western Himalaya Region (WHR) of India using common predictors from ten Global Climate Model (GCM) of CMIP5 (Coupled Model intercomparison Project phase 5) and reanalysis datasets from NCEP/NCAR datasets ( National Centers for Environmental Prediction/National Center for Atmospheric Research) ; and predictands from the IMD (India Meteorological Department) rain gauge stations. Combined EOF (Empirical Orthogonal Function) approach has been used to develop stations specific statistical downscaling models over the WHR and later on some statistical skill scores based on error and agreement analysis were used to validate the model performance. Downscaled precipitation scenario using multi model ensemble of GCM under RCP4.5 (Representative concentration pathways 4.5) revealed a wetter climate during the 2020s, 2050s and 2080s in the annual and monsoon time scale, whereas a drier climate is expected in the winter season. Results reveal a possible intensification of south-west monsoon and decrease in the frequency of western disturbances in the 21 st century as the percentage changes of rainfall in monsoon were higher compared to annual and winter timescale. The uncertainty in the monthly precipitation is predicted to increase as the time progresses during 2020s to 2080s. Higher uncertainty in precipitation is expected in the late pre-monsoon months and early post-monsoon month over the study region.