bluuebunny/crossref_metadata_2025 huggingface dataset:
A Study on Synoptic Conditions Leading to the Extreme Rainfall in Taiwan during 10–12 June 2012
Authors: Wang An-Hsiang , Wang Chung-Chieh , Chen George Tai-Jen
Published: September 2021

During 10–12 June 2012, heavy rainfall occurred three days in a row in southern and central Taiwan, with daily rainfall maxima exceeding 500 mm on each day. In the Mei-yu season (May–June) during 1993–2000, only two other rainfall events had a comparable amount and duration, but this case was the only one that occurred well before the arrival of the Mei-yu front. The synoptic conditions and their evolution leading to this unique event are thus important and are the foci of this study. Our analysis indicates that the 10–12 June 2012 event in Taiwan was caused by the strong and persistent west-southwesterly low-level jet (LLJ) that transported warm, moist, and unstable air from upstream and then impinged on the island. The LLJ developed due to the enhanced horizontal pressure (or height) gradient when the pressure at low-levels fell significantly (by ~8 hPa) in South China (north of the jet) during 8–10 June, but the subtropical high to the southeast maintained its strength. Further, through a diagnosis using the pressure tendency equation, it is found that both warm air advection and the dynamic effects (column divergence and transport of mass by vertical motion) contributed to the pressure fall in South China. The warm air advection occurred in the southern part of a large-scale confluent pattern in China, and the persistent west-southwesterly flow through deep layer (mainly above 800 hPa) in South China transported warmer and less dense air into the region from lower latitudes. On the other hand, South China was also located under the diffluent zone in the northeastern quadrant of the South Asian upper-level anticyclone, which strengthened during 5–10 June and provided divergence aloft, which exceeded the low-level convergence and upward transport of mass (at a fixed height) into the column by vertical motion on 9 June. As a result, the dynamic effects also contributed to the pressure fall, although secondary to the warm air advection. The destabilization process in South China during 8–10 June was also helpful to increase convective activity and upper-level divergence.
Optimal Estimation MSG-SEVIRI Clear-Sky Total Column Water Vapour Retrieval Using the Split Window Difference
Authors: El Kassar Jan El , Carbajal Henken Cintia , Preusker Rene , Fischer Jürgen
Published: September 2021

A new algorithm for the retrieval of day-time total column water vapour (TCWV) from measurements of a MSG-SEVIRI (Meteosat Second Generation Spinning Enhanced Visible and Infrared Imager) instrument is presented. The retrieval is based on a forward operator, at the core of which lies Radiative Transfer for TIROS Operational Vertical Sounder (RTTOV). This forward model relates TCWV and surface temperature to brightness temperatures in the split window at 11 and 12µm with the use of a first guess for temperature and humidity profiles from the ERA5 reanalysis. The forward model is then embedded in a full Optimal Estimation (OE) method, which yields pixel by pixel uncertainty estimates and performance indicators. The algorithm is applicable to any instrument which features the split window configuration, given a first guess for atmospheric conditions (i.e., from NWP) and an estimate of surface emissivity at 11 µm. The algorithm was developed within the framework of RealPEP (Near-Realtime Quantitative Precipitation Estimation and Prediction) in which the advancement of the estimation and nowcasting of extreme precipitation and flooding in Germany are studied. Thus, processing and validation has been limited to the German domain. Three independent ground-based TCWV observation data sets were used as reference, i.e., AERONET (Aerosol Robotic Network), GNSS Germany (Global Navigation Satellite System) and measurements from two MWR (Microwave Radiometer) sites. The validation concludes with good agreement, with absolute biases between 0.11 and 2.85 kg/m2, root mean square deviations (rmsds) between 1.63 and 3.24 kg/m2 and Pearson correlation coefficients ranging from 0.96 to 0.98. The retrievals uncertainty estimates were evaluated against AERONET. The comparison suggests that, in sum, uncertainties are estimated well, while still some error sources seem to be over- and underestimated. In limited case studies it could be shown that SEVIRI TCWV is capable to both display large scale variabilities in water vapour fields and reproduce the daily course of water vapour exposed by ground-based observations.
Revisiting a Classic Identity That Implies the Rogers–Ramanujan Identities II
Authors: Chan Hei-Chi
Published: September 2021

We give a new proof of an identity due to Ramanujan. From this identity, he deduced the famous Rogers–Ramanujan identities. We prove this identity by establishing a simple recursion Jk=qkJk−1, where |q|<1. This is a sequel to our recent work.
Thalamus Atrophy in the Peri-Pregnancy Period in Clinically Stable Multiple Sclerosis Patients: Preliminary Results
Authors: Rościszewska-Żukowska Iwona , Podyma Marek , Stasiołek Mariusz , Siger Małgorzata
Published: September 2021

Radiological activity in the post-partum period in MS patients is a well-known phenomenon, but there is no data concerning the influence of pregnancy on regional brain atrophy. The aim of this article was to investigate local brain atrophy in the peri-pregnancy period (PPP) in patients with MS. Thalamic volume (TV); corpus callosum volume (CCV) and classical MRI activity (new gadolinium enhancing lesions (Gd+), new T2 lesions, T1 lesions volume (T1LV) and T2 lesions volume (T2LV)) were analyzed in 12 clinically stable women with relapsing–remitting MS and with MRI performed in the PPP. We showed that there was a significant decrease in TV (p = 0.021) in the PPP. We also observed a significant increase in the T1 lesion volume (p = 0.028), new gadolinium-enhanced and new T2 lesions (in 46% and 77% of the scans, respectively) in the post-partum period. Our results suggest that the PPP in MS may be associated not only with classical MRI activity but, also, with regional brain atrophy.
Brain Functional Network Architecture Reorganization and Alterations of Positive and Negative Affect, Experiencing Pleasure and Daytime Sleepiness in Cataract Patients after Intraocular Lenses Implantation
Authors: Sobczak Anna Maria , Bohaterewicz Bartosz , Fafrowicz Magdalena , Zyrkowska Aleksandra , Golonka Natalia , Domagalik Aleksandra , Beldzik Ewa , Oginska Halszka , Rekas Marek , Bronicki Dominik , Romanowska-Dixon Bozena , Bolsega-Pacud Joanna , Karwowski Waldemar , Farahani Farzad , Marek Tadeusz
Published: September 2021

Background: Cataracts are associated with progressive blindness, and despite the decline in prevalence in recent years, it remains a major global health problem. Cataract extraction is reported to influence not only perception, attention and memory but also daytime sleepiness, ability to experience pleasure and positive and negative affect. However, when it comes to the latter, the magnitude and prevalence of this effect still remains uncertain. The current study aims to evaluate the hemodynamic basis of daytime sleepiness, ability to experience pleasure and positive and negative affect in cataract patients after the intraocular lens (IOL) implantation. Methods: Thirty-four cataract patients underwent resting-state functional magnetic resonance imaging evaluation before and after cataract extraction and intraocular lens implantation. Both global and local graph metrics were calculated in order to investigate the hemodynamic basis of excessive sleepiness (ESS), experiencing pleasure (SHAPS) as well as positive and negative affect (PANAS) in cataract patients. Results: Eigenvector centrality and clustering coefficient alterations associated with cataract extraction are significantly correlated with excessive sleepiness, experiencing pleasure as well as positive and negative affect. Conclusions: The current study reveals the hemodynamic basis of sleepiness, pleasure and affect in patients after cataract extraction and intraocular lens implantation. The aforementioned mechanism constitutes a proof for changes in functional network activity associated with postoperative vision improvement.
Symptoms of Autism Spectrum Disorder in Individuals with Down Syndrome
Authors: Dimachkie Nunnally Amanda , Nguyen Vivian , Anglo Claudine , Sterling Audra , Edgin Jamie , Sherman Stephanie , Berry-Kravis Elizabeth , del Hoyo Soriano Laura , Abbeduto Leonard , Thurman Angela John
Published: September 2021

There is a growing body of evidence to suggest that individuals with Down syndrome (DS) are diagnosed with autism spectrum disorders (ASD) at a higher rate than individuals in the general population. Nonetheless, little is known regarding the unique presentation of ASD symptoms in DS. The current study aims to explore the prevalence and profiles of ASD symptoms in a sample of individuals with DS (n = 83), aged between 6 and 23 years. Analysis of this sample (MAge = 15.13) revealed that approximately 37% of the sample met the classification cut-off for ASD using the Autism Diagnostic Observation Schedule 2 (ADOS-2) Calibrated Severity Score (CSS), an indicator of the participants’ severity of ASD-related symptoms. Item-level analyses revealed that multiple items on Module 2 and Module 3 of the ADOS-2, mostly in the Social Affect (SA) subdomain, differentiated the children with DS who did not meet ASD classification (DS-only) from those who did (DS + ASD). Lastly, comparisons of individuals with DS-only and those with DS + ASD differed significantly on the syntactic complexity of their expressive language. These findings shed light on the unique presentation of ASD symptoms in a sample of individuals with DS and suggest that expressive language abilities may play a pivotal role in the presentation of ASD symptoms in DS.
Pertuzumab and Trastuzumab Combination with Concomitant Locoregional Radiotherapy for the Treatment of Breast Cancers with HER2 Receptor Overexpression
Authors: Aboudaram Amélie , Loap Pierre , Loirat Delphine , Dhia Syrine Ben , Cao Kim , Fourquet Alain , Kirova Youlia
Published: September 2021

Background: The combination of pertuzumab and trastuzumab dual HER2 blockade with concomitant curative dose locoregional breast radiotherapy in patients with metastatic breast cancer is an important part of treatment strategy. Methods: This was a retrospective study conducted at the Institut Curie on all patients treated concomitantly with pertuzumab/trastuzumab and locoregional breast radiotherapy. Toxicity was evaluated according to the NCICTCAEv4.0. Overall survival, progression-free survival and locoregional recurrence-free survival were evaluated in metastatic patients who were initially well controlled by chemotherapy, for whom local treatment was decided by the multidisciplinary team. Results: Fifty-five patients treated between October 2013 and December 2019 were included, with a median follow-up of 4.1 years. The median age was 53 years (range: 28–81). All patients received curative dose radiotherapy (RT) concomitantly with pertuzumab and trastuzumab (Pertu/Trastu). The median radiation dose was 50 Gy. Safety evaluation did not reveal any significant adverse effects, with 3 cases of grade 3 radiodermatitis (5.4%), but no significant gastrointestinal or cardiac toxicity. The mean difference in LVEF before any chemotherapy and after radiotherapy was −2.43% (p < 0.01). Conclusions: This study demonstrates that the combination of locoregional breast RT with dual HER2 blockade by Pertu/Trastu was very well tolerated, suggesting that RT can be safely administered to patients with HER2-positive breast cancer.
Anus-Preserving Surgery in Advanced Low-Lying Rectal Cancer: A Perspective on Oncological Safety of Intersphincteric Resection
Authors: Piozzi Guglielmo Niccolò , Baek Se-Jin , Kwak Jung-Myun , Kim Jin , Kim Seon Hahn
Published: September 2021

The surgical management of low-lying rectal cancer, within 5 cm from the anal verge (AV), is challenging due to the possibility, or not, to preserve the anus with its sphincter muscles maintaining oncological safety. The standardization of total mesorectal excision, the adoption of neoadjuvant chemoradiotherapy, the implementation of rectal magnetic resonance imaging, and the evolution of mechanical staplers have increased the rate of anus-preserving surgeries. Moreover, extensive anatomy and physiology studies have increased the understanding of the complexity of the deep pelvis. Intersphincteric resection (ISR) was introduced nearly three decades ago as the ultimate anus-preserving surgery. The definition and indication of ISR have changed over time. The adoption of the robotic platform provides excellent perioperative results with no differences in oncological outcomes. Pushing the boundaries of anus-preserving surgeries has risen doubts on oncological safety in order to preserve function. This review critically discusses the oncological safety of ISR by evaluating the anatomical characteristics of the deep pelvis, the clinical indications, the role of distal and circumferential resection margins, the role of the neoadjuvant chemoradiotherapy, the outcomes between surgical approaches (open, laparoscopic, and robotic), the comparison with abdominoperineal resection, the risk factors for oncological outcomes and local recurrence, the patterns of local recurrences after ISR, considerations on functional outcomes after ISR, and learning curve and surgical education on ISR.
Therapeutic Effects of Inhibition of Sphingosine-1-Phosphate Signaling in HIF-2α Inhibitor-Resistant Clear Cell Renal Cell Carcinoma
Authors: Hoefflin Rouven , Harlander Sabine , Abhari Behnaz A. , Peighambari Asin , Adlesic Mojca , Seidel Philipp , Zodel Kyra , Haug Stefan , Göcmen Burulca , Li Yong , Lahrmann Bernd , Grabe Niels , Heide Danijela , Boerries Melanie , Köttgen Anna , Heikenwalder Mathias , Frew Ian J.
Published: September 2021

Specific inhibitors of HIF-2α have recently been approved for the treatment of ccRCC in VHL disease patients and have shown encouraging results in clinical trials for metastatic sporadic ccRCC. However, not all patients respond to therapy and pre-clinical and clinical studies indicate that intrinsic as well as acquired resistance mechanisms to HIF-2α inhibitors are likely to represent upcoming clinical challenges. It would be desirable to have additional therapeutic options for the treatment of HIF-2α inhibitor resistant ccRCCs. Here we investigated the effects on tumor growth and on the tumor microenvironment of three different direct and indirect HIF-α inhibitors, namely the HIF-2α-specific inhibitor PT2399, the dual HIF-1α/HIF-2α inhibitor Acriflavine, and the S1P signaling pathway inhibitor FTY720, in the autochthonous Vhl/Trp53/Rb1 mutant ccRCC mouse model and validated these findings in human ccRCC cell culture models. We show that FTY720 and Acriflavine exhibit therapeutic activity in several different settings of HIF-2α inhibitor resistance. We also identify that HIF-2α inhibition strongly suppresses T cell activation in ccRCC. These findings suggest prioritization of sphingosine pathway inhibitors for clinical testing in ccRCC patients and also suggest that HIF-2α inhibitors may inhibit anti-tumor immunity and might therefore be contraindicated for combination therapies with immune checkpoint inhibitors.
Precision Postoperative Radiotherapy in Sinonasal Carcinomas after Endonasal Endoscopic Surgery
Authors: Thariat Juliette , Carsuzaa Florent , Marcy Pierre Yves , Verillaud Benjamin , de Gabory Ludovic , Ferrand Francois Regis
Published: September 2021

Radiotherapy plays an important role in the treatment of sinonasal cancer, mainly in the adjuvant setting after surgical resection. Many technological approaches have been described, including intensity-modulated radiotherapy, concomitant chemoradiotherapy, charged particle therapy or combined approaches. The choice is based on general criteria related to the oncological results and morbidity of each technique and their availability, as well as specific criteria related to the tumor (tumor extensions, pathology and quality of margins). The aims of this review are: (i) to provide an overview of the radiotherapy techniques available for the management of sinonasal malignant tumors and (ii) to describe the constraints and opportunities of radiotherapy owing to the recent developments of endonasal endoscopic surgery. The indication and morbidity of the different techniques will be discussed based on a critical literature review.
Physical Activity after Colorectal Cancer Diagnosis and Mortality in a Nationwide Retrospective Cohort Study
Authors: Lee Meesun , Lee Yunseo , Jang Doeun , Shin Aesun
Published: September 2021

Physical activity reduces the risk of colon cancer, but its prognostic impact after cancer diagnosis remains unclear. To evaluate the association between post-diagnosis activity and cause-specific mortality, we reconstructed a colorectal cancer patient cohort from the 2009–16 Korean National Health Insurance Service (NHIS) database. Subgroup analyses were performed by treatment group. In total, 27,143 colon cancer patients and 16,453 rectal cancer patients were included in the analysis (mean follow-up, 4.3 years; median 4.0 years). In the surgically treated group, a high level of activity (the weighted sum of the frequencies for walking, moderate, and vigorous activity greater than or equal to 3 times/week) was inversely associated with all-cause mortality (colon cancer: HR, 0.79; 95% CI, 0.72 to 0.88; rectal cancer: HR, 0.75; 95% CI, 0.66 to 0.86) and colorectal cancer-specific mortality (colon cancer: HR, 0.85; 95% CI, 0.76 to 0.97; rectal cancer: HR, 0.77; 95% CI, 0.66 to 0.90). No significant results were shown for cardiovascular disease-specific mortality. No association was shown in patients who received chemoradiotherapy without surgery. The present study may provide evidence for post-diagnosis physical activity as a prognostic factor in colorectal cancer, particularly in surgically treated early-stage patients.
Cis-Acting Factors Causing Secondary Epimutations: Impact on the Risk for Cancer and Other Diseases
Authors: Ruiz de la Cruz Miguel , de la Cruz Montoya Aldo Hugo , Rojas Jiménez Ernesto Arturo , Martínez Gregorio Héctor , Díaz Velásquez Clara Estela , Paredes de la Vega Jimena , de la Cruz Hernández-Hernández Fidel , Vaca Paniagua Felipe
Published: September 2021

Epigenetics affects gene expression and contributes to disease development by alterations known as epimutations. Hypermethylation that results in transcriptional silencing of tumor suppressor genes has been described in patients with hereditary cancers and without pathogenic variants in the coding region of cancer susceptibility genes. Although somatic promoter hypermethylation of these genes can occur in later stages of the carcinogenic process, constitutional methylation can be a crucial event during the first steps of tumorigenesis, accelerating tumor development. Primary epimutations originate independently of changes in the DNA sequence, while secondary epimutations are a consequence of a mutation in a cis or trans-acting factor. Secondary epimutations have a genetic basis in cis of the promoter regions of genes involved in familial cancers. This highlights epimutations as a novel carcinogenic mechanism whose contribution to human diseases is underestimated by the scarcity of the variants described. In this review, we provide an overview of secondary epimutations and present evidence of their impact on cancer. We propose the necessity for genetic screening of loci associated with secondary epimutations in familial cancer as part of prevention programs to improve molecular diagnosis, secondary prevention, and reduce the mortality of these diseases.
Management of Resectable Stage III-N2 Non-Small-Cell Lung Cancer (NSCLC) in the Age of Immunotherapy
Authors: Mielgo-Rubio Xabier , Montemuiño Sara , Jiménez Unai , Luna Javier , Cardeña Ana , Mezquita Laura , Martín Margarita , Couñago Felipe
Published: September 2021

Stage III non-small-cell lung cancer (NSCLC) with N2 lymph node involvement is a heterogeneous group with different potential therapeutic approaches. Patients with potentially resectable III-N2 NSCLC are those who are considered to be able to receive a multimodality treatment that includes tumour resection after neoadjuvant therapy. Current treatment for these patients is based on neoadjuvant chemotherapy +/− radiotherapy followed by surgery and subsequent assessment for adjuvant chemotherapy and/or radiotherapy. In addition, some selected III-N2 patients could receive upfront surgery or pathologic N2 incidental involvement can be found a posteriori during analysis of the surgical specimen. The standard treatment for these patients is adjuvant chemotherapy and evaluation for complementary radiotherapy. Despite being a locally advanced stage, the cure rate for these patients continues to be low, with a broad improvement margin. The most immediate hope for improving survival data and curing these patients relies on integrating immunotherapy into perioperative treatment. Immunotherapy based on anti-PD1/PD-L1 immune checkpoint inhibitors is already a standard treatment in stage III unresectable and advanced NSCLC. Data from the first phase II studies in monotherapy neoadjuvant therapy and, in particular, in combination with chemotherapy, are highly promising, with impressive improved and complete pathological response rates. Despite the lack of confirmatory data from phase III trials and long-term survival data, and in spite of various unresolved questions, immunotherapy will soon be incorporated into the armamentarium for treating stage III-N2 NSCLC. In this article, we review all therapeutic approaches to stage III-N2 NSCLC, analysing both completed and ongoing studies that evaluate the addition of immunotherapy with or without chemotherapy and/or radiotherapy.
DNA Methylation Age Drift Is Associated with Poor Outcomes and De-Differentiation in Papillary and Follicular Thyroid Carcinomas
Authors: Liu Tiantian , Wang Jiansheng , Xiu Yuchen , Wu Yujiao , Xu Dawei
Published: September 2021

Alterations in global DNA methylation play a critical role in both aging and cancer, and DNA methylation (DNAm) age drift has been implicated in cancer risk and pathogenesis. In the present study, we analyzed the TCGA cohort of papillary and follicular thyroid carcinoma (PTC and FTC) for their DNAm age and association with clinic-pathological features. In 54 noncancerous thyroid (NT) samples, DNAm age was highly correlated with patient chronological age (R2 = 0.928, p = 2.6 × 10−31), but drifted to younger than chronological age in most specimens, especially those from patients >50 years old. DNAm age in 502 tumors was also correlated with patient chronological age, but to a much lesser extent (R2 = 0.403). Highly drifted DNAm age (HDDA) was identified in 161 tumors, among which were 101 with DNAm age acceleration while 60 with DNAm age deceleration. Tumors with HDDA were characterized by the robust aberrations in metabolic activities, extracellular microenvironment components and inflammation/immunology responses, and dedifferentiation. Importantly, HDDA in tumors independently predicted shorter disease-free survival of patients. Collectively, NT thyroids from TC patients have younger DNAm age, while HDDA frequently occurs in TCs, and contributes to the TC progression and poor patient outcomes. HDDA may serve as a new prognostic factor for TCs.
The FHP01 DDX3X Helicase Inhibitor Exerts Potent Anti-Tumor Activity In Vivo in Breast Cancer Pre-Clinical Models
Authors: Gherardini Lisa , Inzalaco Giovanni , Imperatore Francesco , D’Aurizio Romina , Franci Lorenzo , Miragliotta Vincenzo , Boccuto Adele , Calandro Pierpaolo , Andreini Matteo , Tarditi Alessia , Chiariello Mario
Published: September 2021

Inhibition of DDX3X expression or activity reduces proliferation in cells from various tumor tissues, in particular in breast cancer, and its expression often correlates to tumor aggressiveness. This makes DDX3X a prominent candidate for the design of drugs for novel personalized therapeutic strategies. Starting from an in silico drug discovery approach, a group of molecules has been selected by molecular docking at the RNA binding site of DDX3X. Here, the most promising among them, FHP01, was evaluated in breast cancer preclinical models. Specifically, FHP01 exhibited very effective antiproliferative and killing activity against different breast cancer cell types, among which those from triple-negative breast cancer (TNBC). Interestingly, FHP01 also inhibited WNT signaling, a key tumorigenic pathway already correlated to DDX3X functions in breast cancer model cell lines. Ultimately, FHP01 also caused a significant reduction, in vivo, in the growth of MDA MB 231-derived TNBC xenograft models. Importantly, FHP01 showed good bioavailability and no toxicity on normal peripheral blood mononuclear cells in vitro and on several mouse tissues in vivo. Overall, our data suggest that the use of FHP01 and its related compounds may represent a novel therapeutic approach with high potential against breast cancer, including the triple-negative subtype usually correlated to the most unfavorable outcomes because of the lack of available targeted therapies.
Profiling Cisplatin Resistance in Head and Neck Cancer: A Critical Role of the VRAC Ion Channel for Chemoresistance
Authors: Siemer Svenja , Fauth Torsten , Scholz Paul , Al-Zamel Yara , Khamis Aya , Gül Désirée , Freudelsperger Laura , Wollenberg Barbara , Becker Sven , Stauber Roland H. , Hagemann Jan
Published: September 2021

Treatment success of head and neck cancers (HNSCC) is often hindered by tumor relapses due to therapy resistances. This study aimed at profiling cisplatin resistance mechanisms and identifying biomarkers potentially suitable as drug targets and for patient stratification. Bioinformatic analyses of suggested resistance factors in a cohort of 565 HNSCC patients identified the VRAC ion channel as a clinically relevant indicator for recurrent diseases following radiochemotherapy (p = 0.042). Other drug import/export transporters, such as CTR1, OCT1, or MRP1, were found to be less relevant. To experimentally verify VRAC’s critical role for cisplatin resistance, we used CRISPR/Cas9 knockout resulting in cisplatin-resistant HNSCC cells, which could be resensitized by VRAC expression. Next-generation sequencing further underlined VRAC’s importance and identified VRAC-regulated signaling networks, potentially also contributing to cisplatin resistance. CTR1, OCT1, or MRP1 did not contribute to increased cisplatin resistance. In addition to two-dimensional HNSCC models, three-dimensional tumor spheroid cultures confirmed VRAC’s unique role for cisplatin sensitivity. Here, resistance correlated with DNA damage and downstream apoptosis. The cisplatin specificity of the identified VRAC pathway was verified by testing paclitaxel and doxorubicin. Our results were independently confirmed in naturally occurring, cisplatin-resistant HNSCC cancer cell models. Collectively, we here demonstrate VRAC’s role for cisplatin resistance in HNSCC and its relevance as a potential drug target and/or prognostic biomarker for chemotherapy resistance.
Deep Learning to Decipher the Progression and Morphology of Axonal Degeneration
Authors: Palumbo Alex , Grüning Philipp , Landt Svenja Kim , Heckmann Lara Eleen , Bartram Luisa , Pabst Alessa , Flory Charlotte , Ikhsan Maulana , Pietsch Sören , Schulz Reinhard , Kren Christopher , Koop Norbert , Boltze Johannes , Madany Mamlouk Amir , Zille Marietta
Published: September 2021

Axonal degeneration (AxD) is a pathological hallmark of many neurodegenerative diseases. Deciphering the morphological patterns of AxD will help to understand the underlying mechanisms and develop effective therapies. Here, we evaluated the progression of AxD in cortical neurons using a novel microfluidic device together with a deep learning tool that we developed for the enhanced-throughput analysis of AxD on microscopic images. The trained convolutional neural network (CNN) sensitively and specifically segmented the features of AxD including axons, axonal swellings, and axonal fragments. Its performance exceeded that of the human evaluators. In an in vitro model of AxD in hemorrhagic stroke induced by the hemolysis product hemin, we detected a time-dependent degeneration of axons leading to a decrease in axon area, while axonal swelling and fragment areas increased. Axonal swellings preceded axon fragmentation, suggesting that swellings may be reliable predictors of AxD. Using a recurrent neural network (RNN), we identified four morphological patterns of AxD (granular, retraction, swelling, and transport degeneration). These findings indicate a morphological heterogeneity of AxD in hemorrhagic stroke. Our EntireAxon platform enables the systematic analysis of axons and AxD in time-lapse microscopy and unravels a so-far unknown intricacy in which AxD can occur in a disease context.
Formins in Human Disease
Authors: Labat-de-Hoz Leticia , Alonso Miguel A.
Published: September 2021

Almost 25 years have passed since a mutation of a formin gene, DIAPH1, was identified as being responsible for a human inherited disorder: a form of sensorineural hearing loss. Since then, our knowledge of the links between formins and disease has deepened considerably. Mutations of DIAPH1 and six other formin genes (DAAM2, DIAPH2, DIAPH3, FMN2, INF2 and FHOD3) have been identified as the genetic cause of a variety of inherited human disorders, including intellectual disability, renal disease, peripheral neuropathy, thrombocytopenia, primary ovarian insufficiency, hearing loss and cardiomyopathy. In addition, alterations in formin genes have been associated with a variety of pathological conditions, including developmental defects affecting the heart, nervous system and kidney, aging-related diseases, and cancer. This review summarizes the most recent discoveries about the involvement of formin alterations in monogenic disorders and other human pathological conditions, especially cancer, with which they have been associated. In vitro results and experiments in modified animal models are discussed. Finally, we outline the directions for future research in this field.
Realization of III-Nitride c-Plane microLEDs Emitting from 470 to 645 nm on Semi-Relaxed Substrates Enabled by V-Defect-Free Base Layers
Authors: White Ryan C. , Khoury Michel , Wong Matthew S. , Li Hongjian , Lynsky Cheyenne , Iza Michael , Keller Stacia , Sotta David , Nakamura Shuji , DenBaars Steven P.
Published: September 2021

We examine full InGaN-based microLEDs on c-plane semi-relaxed InGaN substrates grown by metal organic chemical vapor deposition (MOCVD) that operate across a wide range of emission wavelengths covering nearly the entire visible spectrum. By employing a periodic InGaN base layer structure with high temperature (HT) GaN interlayers on these semi-relaxed substrates, we demonstrate robust μLED devices. A broad range of emission wavelengths ranging from cyan to deep red are realized, leveraging the indium incorporation benefit of the relaxed InGaN substrate with an enlarged lattice parameter. Since a broad range of emission wavelengths can be realized, this base layer scheme allows the tailoring of the emission wavelength to a particular application, including the possibility for nitride LEDs to emit over the entire visible light spectrum. The range of emission possibilities from blue to red makes the relaxed substrate and periodic base layer scheme an attractive platform to unify the visible emission spectra under one singular material system using III-Nitride MOCVD.
Targeted Chemotherapy Delivery via Gold Nanoparticles: A Scoping Review of In Vivo Studies
Authors: Morărașu Ștefan , Iacob Ștefan , Tudorancea Ionuț , Luncă Sorinel , Dimofte Mihail-Gabriel
Published: September 2021

In the field of oncology, a lot of improvements in nanotechnology creates support for better diagnosis and therapeutic opportunities, and due to their physical and chemical properties, gold nanoparticles are highly applicable. We performed a literature review on the studies engaging the usage of gold nanoparticles on murine models with a focus on the type of the carrier, the chemotherapy drug, the target tumoral tissue and outcomes. We identified fifteen studies that fulfilled our search criteria, in which we analyzed the synthesis methods, the most used chemotherapy conjugates of gold nanoparticles in experimental cancer treatment, as well as the improved impact on tumor size and system toxicity. Due to their intrinsic traits, we conclude that chemotherapy conjugates of gold nanoparticles are promising in experimental cancer treatment and may prove to be a safer and improved therapy option than current alternatives.
Organic Inorganic Hybrid Perovskite Solar Cells
Authors: Wang Ryan T. , Xu Gu
Published: September 2021

Much progress has been achieved in the commercialization of solar devices, especially perovskite solar cells, which have shown excellent transport properties and low fabrication costs [...]
Penetration of Chitosan into the Single Walled Armchair Carbon Nanotubes: Atomic Scale Insight
Authors: Razzokov Jamoliddin , Marimuthu Parthiban , Saidov Kamoladdin , Ruzimuradov Olim , Mamatkulov Shavkat
Published: September 2021

(1) Background: Currently, nanomaterials have been broadly used in various applications including engineering, medicine and biology. One of the carbon allotropes such as carbon nanotubes (CNTs) implemented for fabrication of nanocomposite materials due to the hypersensitivity. The combined design of nanomaterial with chitosan (CS) and CNT expands the field of exploitation from biosensing and tissue engineering to water desalination. Therefore, the penetration of CS into CNT provides a valuable insight into the interactions between CS and CNT. (2) Methods: We performed molecular dynamics simulations, applying the umbrella sampling method, in order to calculate the potential mean force between CS and CNT. (3) Results: The estimated penetration free energies showed that CS is favorable to the penetration into CNT cavities. However, the penetration nature differs depending on the CNT’s architecture. (4) Conclusions: Our finding revealed the CS penetration process into CNT with nanoscale precision. The investigation results assist in a better understanding of the nanocomposite materials based on CS-CNT.
Using Ecological Niche Models for Population and Range Estimates of a Threatened Snake Species (Crotalus oreganus) in Canada
Authors: Kirk David Anthony , Karimi Sahebeh , Maida Jared R. , Harvey Jessica A. , Larsen Karl W. , Bishop Christine A.
Published: September 2021

Modelling the distribution and abundance of species at risk is extremely important for their conservation and management. We used ecological niche models (ENMs) to predict the occurrence of western rattlesnakes (Crotalus oreganus) in British Columbia (BC), Canada. We applied this to existing population estimates to support a threshold of occurrence for management and conservation. We also identified predictors influencing rattlesnake distribution and abundance in this region. Using a Geographic Information Systems platform, we incorporated ENMs, capture–mark–recapture (CMR) and radio-telemetry results, province-wide observations, Landsat imagery and provincial databases for agricultural land use to produce quantitative, spatially explicit, population estimates across BC. Using available western rattlesnake habitat estimated at 183.9 km2 and averaging estimates calculated from densities in three study populations, we generated a mean adult population size of 9722 (±SD 3009; 0.8 relative index of occurrence [RIO] threshold). Only a small area (21.6 km2) of suitable land cover was located within protected areas, potentially protecting an estimated 1144 (±354) adults. Most suitable land cover was within 500 m of roads (170.6 km2), representing potential habitat being used by an estimated 9017 (±2791) adults. At the threshold RIO value chosen (0.8), only a very small area of farmland provided suitable land cover. Our results highlight the possibility of high mortality rates for western rattlesnakes near roads and the fact that protected areas do not provide sufficient coverage to conserve the population. Given that this species has relatively low mobility and high site fidelity to home ranges, our population estimate for BC provides a useful reference for the northern part of the species’ range. It also fulfills a need to estimate population size within political jurisdictions where conservation management decisions are made, as well as presenting a method that can be applied to other parts of the range, including the southern United States. Our study provides an important benchmark for future monitoring of western rattlesnakes in BC using a repeatable and transparent approach. Similar applications can be extrapolated and applied for other threatened species to identify and quantify population distributions and threats, further supporting conservation prioritization tools to be used to maximize the effectiveness of conservation strategies under financial constraints.
Impact of Algicidal Bacillus mycoides on Diatom Ulnaria acus from Lake Baikal
Authors: Bedoshvili Yekaterina , Bayramova Elvira , Sudakov Nikolay , Klimenkov Igor , Kurilkina Maria , Likhoshway Yelena , Zakharova Yulia
Published: September 2021

Algae–bacteria interactions play an important role in water ecosystems. In this work, the BS2-15 algicidal strain was isolated from the bottom sediments of Lake Baikal and identified as Bacillus mycoides on the basis of 16S rDNA sequencing, its described ultrastructure, and biochemical properties. B. mycoides BS2-15 was demonstrated to have a strong algicidal effect against a freshwater diatom culture of Ulnaria acus, inhibiting its growth and increasing frustules fragility. By analyzing the impact of bacterial filtrate onto the cells of U. acus, we demonstrated that perhaps an algicidal compound is produced by bacteria independently in the presence of diatoms in a medium. Using methods of TUNEL and confocal microscopy, we revealed that the bacterial algicidal effect on the diatom cells results in DNA fragmentation, nucleus destruction, and neutral lipid accumulation. This phenomenon highlights the complexity of algae–bacteria interactions and their potential role in regulating water ecosystem microbial populations.
Discriminable Multi-Label Attribute Selection for Pre-Course Student Performance Prediction
Authors: Yang Jie , Hu Shimin , Wang Qichao , Fong Simon
Published: September 2021

The university curriculum is a systematic and organic study complex with some immediate associated steps; the initial learning of each semester’s course is crucial, and significantly impacts the learning process of subsequent courses and further studies. However, the low teacher–student ratio makes it difficult for teachers to consistently follow up on the detail-oriented learning situation of individual students. The extant learning early warning system is committed to automatically detecting whether students have potential difficulties—or even the risk of failing, or non-pass reports—before starting the course. Previous related research has the following three problems: first of all, it mainly focused on e-learning platforms and relied on online activity data, which was not suitable for traditional teaching scenarios; secondly, most current methods can only proffer predictions when the course is in progress, or even approaching the end; thirdly, few studies have focused on the feature redundancy in these learning data. Aiming at the traditional classroom teaching scenario, this paper transforms the pre-class student performance prediction problem into a multi-label learning model, and uses the attribute reduction method to scientifically streamline the characteristic information of the courses taken and explore the important relationship between the characteristics of the previously learned courses and the attributes of the courses to be taken, in order to detect high-risk students in each course before the course begins. Extensive experiments were conducted on 10 real-world datasets, and the results proved that the proposed approach achieves better performance than most other advanced methods in multi-label classification evaluation metrics.
Chaotic Entanglement: Entropy and Geometry
Authors: Morena Matthew A. , Short Kevin M.
Published: September 2021

In chaotic entanglement, pairs of interacting classically-chaotic systems are induced into a state of mutual stabilization that can be maintained without external controls and that exhibits several properties consistent with quantum entanglement. In such a state, the chaotic behavior of each system is stabilized onto one of the system’s many unstable periodic orbits (generally located densely on the associated attractor), and the ensuing periodicity of each system is sustained by the symbolic dynamics of its partner system, and vice versa. Notably, chaotic entanglement is an entropy-reversing event: the entropy of each member of an entangled pair decreases to zero when each system collapses onto a given period orbit. In this paper, we discuss the role that entropy plays in chaotic entanglement. We also describe the geometry that arises when pairs of entangled chaotic systems organize into coherent structures that range in complexity from simple tripartite lattices to more involved patterns. We conclude with a discussion of future research directions.
Bayesian Analysis of Dynamic Cumulative Residual Entropy for Lindley Distribution
Authors: Almarashi Abdullah M. , Algarni Ali , Hassan Amal S. , Zaky Ahmed N. , Elgarhy Mohammed
Published: September 2021

Dynamic cumulative residual (DCR) entropy is a valuable randomness metric that may be used in survival analysis. The Bayesian estimator of the DCR Rényi entropy (DCRRéE) for the Lindley distribution using the gamma prior is discussed in this article. Using a number of selective loss functions, the Bayesian estimator and the Bayesian credible interval are calculated. In order to compare the theoretical results, a Monte Carlo simulation experiment is proposed. Generally, we note that for a small true value of the DCRRéE, the Bayesian estimates under the linear exponential loss function are favorable compared to the others based on this simulation study. Furthermore, for large true values of the DCRRéE, the Bayesian estimate under the precautionary loss function is more suitable than the others. The Bayesian estimates of the DCRRéE work well when increasing the sample size. Real-world data is evaluated for further clarification, allowing the theoretical results to be validated.
Older People’s Media Repertoires, Digital Competences and Media Literacies: A Case Study from Italy
Authors: Carenzio Alessandra , Ferrari Simona , Rasi Päivi
Published: September 2021

Digital media are part of everyday life and have an intergenerational appeal, entering older people’s agendas, practices, and habits. Many people aged over 60 years lack adequate digital competences and media literacies to support learning, well-being, and participation in society, thus imposing a need to discuss older people’s willingness, opportunities, and abilities to use digital media. This study explored older people’s media use and repertoires, digital competences, and media literacies to promote media literacy education across all ages. The article discusses the data from 24 interviews with older people aged 65 to 98 years in Italy to answer the following research questions: What kinds of media repertoires emerge? What kinds of competences and media literacies can be described? What kinds of support and training do older people get and wish to receive? The analysis of the data produced four specific profiles concerning media repertoires: analogic, accidental, digital-instrumental, and hybridised users. Media literacy is still a critical framework, but the interviewees were open to opportunities to improve their competences. The use of digital media has received a strong boost due to the pandemic, as digital media have been the only way to get in touch with others and carry out their daily routine.
Local Renewable Energy Development: School Teachers’ Perceptions, Attitudes and Teaching Intentions
Authors: Liarakou Georgia , Konstantinidi Alina , Gavrilakis Costas
Published: September 2021

This study investigated factors that might influence teachers’ intention to choose Renewable Energy Sources as an optional module. The research involved 454 Greek teachers working in the archipelagos of the southern Aegean region in Greece, an area with significant potential for the development of Renewable Energy Sources (RES). This potential however remains largely unexploited partly due to local community reluctance towards RES development in the area. Although renewable energy education is considered to be necessary for further RES development, RES are not among teachers’ first choice as an environmental module. We found that, despite teachers demonstrating highly positive attitudes towards RES, they consider local communities to be rather non-supportive of local RES development. A relationship between teachers’ moderate intention to teach RES and teachers’ perceptions of locals as non-supportive towards RES was found. We also found that local teachers feel more competent to teach about RES than non-local teachers. The latter are more motivated to comply with social pressure than locals. These findings emphasize the need for renewable energy education policy makers to take into account local communities’ role in influencing the teaching of RES and to provide teachers with the appropriate skills in order to competently handle potential oppositions.
Structural Power Performance Targets for Future Electric Aircraft
Authors: Karadotcheva Elitza , Nguyen Sang N. , Greenhalgh Emile S. , Shaffer Milo S. P. , Kucernak Anthony R. J. , Linde Peter
Published: September 2021

The development of commercial aviation is being driven by the need to improve efficiency and thereby lower emissions. All-electric aircraft present a route to eliminating direct fuel burning emissions, but their development is stifled by the limitations of current battery energy and power densities. Multifunctional structural power composites, which combine load-bearing and energy-storing functions, offer an alternative to higher-energy-density batteries and will potentially enable lighter and safer electric aircraft. This study investigated the feasibility of integrating structural power composites into future electric aircraft and assessed the impact on emissions. Using the Airbus A320 as a platform, three different electric aircraft configurations were designed conceptually, incorporating structural power composites, slender wings and distributed propulsion. The specific energy and power required for the structural power composites were estimated by determining the aircraft mission performance requirements and weight. Compared to a conventional A320, a parallel hybrid-electric A320 with structural power composites >200 Wh/kg could potentially increase fuel efficiency by 15% for a 1500 km mission. For an all-electric A320, structural power composites >400 Wh/kg could halve the specific energy or mass of batteries needed to power a 1000 km flight.