bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor Microenvironment Modifications Recorded With IVIM Perfusion Analysis and DCE-MRI After Neoadjuvant Radiotherapy: A Preclinical Study
Authors: Lallemand François , Leroi Natacha , Blacher Silvia , Bahri Mohamed Ali , Balteau Evelyne , Coucke Philippe , Noël Agnès , Plenevaux Alain , Martinive Philippe
Published: December 2021

Purpose

Neoadjuvant radiotherapy (NeoRT) improves tumor local control and facilitates tumor resection in many cancers. Some clinical studies demonstrated that both timing of surgery and RT schedule influence tumor dissemination, and subsequently patient overall survival. Previously, we developed a pre-clinical model demonstrating the impact of NeoRT schedule and timing of surgery on metastatic spreading. We report on the impact of NeoRT on tumor microenvironment by MRI.

Methods

According to our NeoRT model, MDA-MB 231 cells were implanted in the flank of SCID mice. Tumors were locally irradiated (PXI X-Rad SmART) with 2x5Gy and then surgically removed at different time points after RT. Diffusion-weighted (DW) and Dynamic contrast enhancement (DCE) MRI images were acquired before RT and every 2 days between RT and surgery. IntraVoxel Incoherent Motion (IVIM) analysis was used to obtain information on intravascular diffusion, related to perfusion (F: perfusion factor) and subsequently tumor vessels perfusion. For DCE-MRI, we performed semi-quantitative analyses.

Results

With this experimental model, a significant and transient increase of the perfusion factor F [50% of the basal value (n=16, p<0.005)] was observed on day 6 after irradiation as well as a significant increase of the WashinSlope with DCE-MRI at day 6 (n=13, p<0.05). Using immunohistochemistry, a significant increase of perfused vessels was highlighted, corresponding to the increase of perfusion in MRI at this same time point. Moreover, Tumor surgical resection during this peak of vascularization results in an increase of metastasis burden (n=10, p<0.05).

Conclusion

Significant differences in perfusion-related parameters (F and WashinSlope) were observed on day 6 in a neoadjuvant radiotherapy model using SCID mice. These modifications are correlated with an increase of perfused vessels in histological analysis and also with an increase of metastasis spreading after the surgical procedure. This experimental observation could potentially result in a way to personalize treatment, by modulating the time of surgery guided on MRI functional data, especially tumor perfusion.
Pegylated Interferon Alpha-2b in Patients With Polycythemia Vera and Essential Thrombocythemia in the Real World
Authors: Sun Yingxin , Cai Yifeng , Cen Jiannong , Zhu Mingqing , Pan Jinlan , Wang Qian , Wu Depei , Chen Suning
Published: December 2021

Several clinical trials have shown promising efficacy of pegylated interferon (Peg-IFN) in the first- and second-line polycythemia vera (PV) and essential thrombocythemia (ET). However, the efficacy and safety of Peg-IFN in the real world have rarely been reported. Hence, we conducted a prospective, single-center, single-arm, open exploratory study, which aimed to explore the hematologic response, molecular response, safety, and tolerability of patients with PV and ET treated with Peg-IFN in the real world. This study included newly diagnosed or previously treated patients with PV and ET, aged 18 years or older, admitted to the Department of Hematology of the First Affiliated Hospital of Soochow University from November 2017 to October 2019. The results revealed that complete hematological response (CHR) was achieved in 66.7% of patients with PV and 76.2% of patients with ET, and the molecular response was obtained in 38.5% of patients with PV and 50% of patients with ET after 48 weeks of Peg-IFN treatment. Peg-IFN is safe, effective and well tolerated in most patients. In the entire cohort, 4 patients (9.1%) discontinued treatment due to drug-related toxicity. In conclusion, Peg-IFN is a promising strategy in myeloproliferative neoplasms (MPNs), and Peg-IFN alone or in combination with other drugs should be further explored to reduce treatment-related toxicity and improve tolerability.
Mutation of Hashimoto’s Thyroiditis and Papillary Thyroid Carcinoma Related Genes and the Screening of Candidate Genes
Authors: Zhang Lizhuo , Zhou Lingyan , Feng Qingqing , Li Qinglin , Ge Minghua
Published: December 2021

Clinical studies have shown similarities in the genetic background and biological functional characteristics between Hashimoto’s thyroiditis (HT) and papillary thyroid carcinoma (PTC), and that HT may increase risks of PTC. Here, we set to determine the gene expression specificity of HT and PTC by screening related genes or co-expressed genes and exploring their genetic correlation. Referencing the Oncomine database, HT-related genes were discovered to be expressed in many different types of thyroid cancer, such as TSHR that is highly expressed in thyroid cancer. An in-depth genetic analysis and verification of 35 cancer and paracancerous tissue pairs from patients with thyroid cancer, and 35 tissues and blood cells pairs from patients with Hashimoto’s thyroiditis was conducted. Gene chip technology research showed that TSHR, BACH2, FOXE1, RNASET2, CTLA4, PTPN22, IL2RA and other HT-related genes were all expressed in PTC, in which TSHR was significantly over-expressed in PTC patients sensitive to radioactive iodine therapy, while BACH2 was significantly under-expressed in these patients. The biologically significant candidate Tag SNP highlighted from HT-related genes was screened by the high-throughput detection method. Somatic mutations in patients with HT and PTC were detected by target region capture technique, and 75 mutations were found in patients with HT and PTC. The upstream regulatory factors of the different genes shared by HT and PTC were analyzed based on Ingenuity Pathway Analysis (IPA), and it was found that HIF-1α and PD-L1 could be used as important upstream regulatory signal molecules. These results provide a basis for screening key diagnostic genes of PTC by highlighting the relationship between some HT-related genes and their polymorphisms in the pathogenesis of PTC.
Parental Feeding Styles and Their Association With Complementary Feeding Practices and Growth in Mexican Children
Authors: Kim-Herrera Edith Y. , Ramírez-Silva Ivonne , Rodríguez-Oliveros Guadalupe , Ortiz-Panozo Eduardo , Sánchez-Estrada Marcela , Rivera-Pasquel Marta , Pérez-Escamilla Rafael , Rivera-Dommarco Juan Angel
Published: December 2021

Background: Complementary feeding practices and corresponding parental feeding styles influence nutritional status in later stages of childhood. Findings on the association of these variables with infant growth remain inconsistent; in Mexico, a research gap exists in this area.

Research Aims: (1) To characterize parental feeding styles and complementary feeding practices, and (2) to evaluate the association of parental feeding styles with complementary feeding practices and infant growth at 6 and 9 months of age.

Methods: Data were collected from a prospective Mexican birth cohort. Parental feeding styles, complementary feeding practices, and anthropometric data from 263 to 234 mother-child pairs (infants of 6 and 9 months of age, respectively) were analyzed. Logistic and linear regression models were used to determine the associations between variables.

Results: The predominant parental feeding style was the “responsive style” (90%). Only 43.7 and 8.1% of 6- and 9-month-old infants, had adequate complementary feeding practices, respectively. At 6 months, mothers who were responsive to satiety signals had 11% lesser possibilities (OR = 0.89, 95% CI [0.80, 0.98]) of their infant having inadequate complementary feeding practices than their counterparts and “pressuring to finish” and “pressuring to eat cereal” sub-constructs were associated with lower weight for length and body mass index Z-scores (p = 0.02).

Conclusions: A high proportion of infants (>40%) did not meet international recommendations. The “pressuring” parental feeding style sub-constructs were associated with growth indicators in 6-month old infants. This emphasizes the importance of promoting parental responsiveness to infant appetite and satiety signals to achieving adequate complementary feeding practices.
Cannabis sativa L. (var. indica) Exhibits Hepatoprotective Effects by Modulating Hepatic Lipid Profile and Mitigating Gluconeogenesis and Cholinergic Dysfunction in Oxidative Hepatic Injury
Authors: Erukainure Ochuko L. , Matsabisa Motlalepula G. , Salau Veronica F. , Oyedemi Sunday O. , Oyenihi Omolola R. , Ibeji Collins U. , Islam Md. Shahidul
Published: December 2021

Cannabis sativa L. is a crop utilized globally for recreational, therapeutic, and religious purposes. Although considered as an illicit drug in most countries, C. sativa until recently started gaining attention for its medicinal application. This study sought to investigate the hepatoprotective effect of C. sativa on iron-mediated oxidative hepatic injury. Hepatic injury was induced ex vivo by incubating hepatic tissues with Fe2+, which led to depleted levels of reduced glutathione, superoxide dismutase, catalase and ENTPDase activities, triglyceride, and high-density lipoprotein–cholesterol (HDL-C). Induction of hepatic injury also caused significant elevation of malondialdehyde, nitric oxide, cholesterol, and low-density lipoprotein–cholesterol (LDL-C) levels while concomitantly elevating the activities of ATPase, glycogen phosphorylase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, amylase, and lipase. Treatment with the hexane, dichloromethane (DCM), and ethanol extracts of C. sativa leaves significantly (p < 0.05) reversed these levels and activities to almost near normal. However, there was no significant effect on the HDL-C level. The extracts also improved the utilization of glucose in Chang liver cells. High-performance liquid chromatography (HPLC) analysis showed the presence of phenolics in all extracts, with the ethanol extract having the highest constituents. Cannabidiol (CBD) was identified in all the extracts, while Δ-9-tetrahydrocannabinol (Δ-9-THC) was identified in the hexane and DCM extracts only. Molecular docking studies revealed strong interactions between CBD and Δ-9-THC with the β2 adrenergic receptor of the adrenergic system. The results demonstrate the potential of C. sativa to protect against oxidative-mediated hepatic injury by stalling oxidative stress, gluconeogenesis, and hepatic lipid accumulation while modulating cholinergic and purinergic activities. These activities may be associated with the synergistic effect of the compounds identified and possible interactions with the adrenergic system.
Ethnopharmacological Survey of Traditional Chinese Medicine Pharmacy Prescriptions for Dysmenorrhea
Authors: Su Kuo-Han , Su Shan-Yu , Ko Chien-Yu , Cheng Yung-Chi , Huang Shyh-Shyun , Chao Jung
Published: December 2021

Chinese herbal medicines have long been used for the treatment of dysmenorrhea. The treatment experiences of traditional Chinese medicine (TCM) pharmacies passed down through generations have contributed to a wealth of prescriptions for dysmenorrhea that have achieved significant therapeutic effects in countless Taiwanese women. Therefore, surveying and analyzing these prescriptions may enable us to elucidate the core medication combinations used in TCM prescriptions for dysmenorrhea. In the present study, a field investigation was conducted on various TCM pharmacies in Taiwan. A total of 96 TCM pharmacies were sampled, and 99 prescriptions for dysmenorrhea containing 77 different medicinal materials were collected. Compositae (8%) was the most common botanical source of the medicinal materials, and the predominant TCM property and flavor of the materials were warm (45%) and sweet (73%), respectively. The blood-activating and stasis-dispelling effect (23%) and the qi-tonifying effect (23%) were the most prevalent traditional effects, and the modern pharmacological effects most commonly found in the materials were anti-inflammatory (73%), antitumor (59%), and analgesic (12%) effects. Network analysis of the 77 medicinal materials used in the prescriptions, which was performed using the Traditional Chinese Medicine Inheritance Support System, yielded seven core medicinal materials and the corresponding network diagram. The seven core medicinal materials ranked in order of relative frequency of citation (RFC) were Angelica sinensis (Oliv.) Diels (Dang Gui), Ligusticum chuanxiong Hort (Chuan Qiong), Rehmannia glutinosa Libosch (Di Huang), Paeonia lactiflora Pall (Bai Shao), Hedysarum polybotrys Hand.-Mazz (Hong Qi), Lycium chinense Mill (Gou Qi Zi), and Cinnamomum cassia (L.). J. Presl (Gui Zhi). A total of 58 combinations, each consisting of two to five of the seven medicinal materials and 107 association rules among the materials, were identified. This study provides a record of valuable knowledge on TCM pharmacy prescriptions for dysmenorrhea. The rich medicinal knowledge of TCM pharmacies in Taiwan is worthy of further exploration, and the results of this study can serve as a basis for future pharmacological research and the development of naturally derived medications for dysmenorrhea.
Key Phytochemicals and Biological Functions of Chuanxiong Rhizoma Against Ischemic Stroke: A Network Pharmacology and Experimental Assessment
Authors: Zeng Peng , Yi Yao , Su Hong-Fei , Ye Chao-Yuan , Sun Yi-Wen , Zhou Xin-Wen , Lu Youming , Shi Anbing , Tian Qing
Published: December 2021

Presently, the treatment options for ischemic stroke (IS) are limited due to the complicated pathological process of the disease. Chuanxiong Rhizome (CR), also known as Conioselinum anthriscoides “Chuanxiong” (rhizome), is the most widely used traditional Chinese medicine for treating stroke. This study aimed to uncover the key phytochemicals and biological functions of CR against IS through a network pharmacology approach combining with IS pathophysiology analysis. We employed permanent unilateral common carotid artery ligation to construct a mouse model of global cerebral ischemia and found that cerebral ischemia injuries were improved after 7 days of gavage treatment of CR (1,300 mg/kg/day). CR exerts protective effects on neurons mainly by acting on targets related to synaptic structure, synaptic function, neuronal survival and neuronal growth. A total of 18 phytochemicals from CR based on UHPLC-MS/MS that corresponded to 85 anti-IS targets. Coniferyl ferulate, neocnidilide and ferulic acid were identified as the key phytochemicals of CR against IS. Its brain protective effects involve anti-inflammatory, anti-oxidative stress, and anti-cell death activities and improves blood circulation. Additionally, the two most important synergistic effects of CR phytochemicals in treating IS are prevention of infection and regulation of blood pressure. In brain samples of Sham mice, L-tryptophan and vanillin were detected, while L-tryptophan, gallic acid, vanillin and cryptochlorogenic acid were detected in IS mice by UHPLC–MS/MS. Our findings provide a pathophysiology relevant pharmacological basis for further researches on IS therapeutic drugs.
Empagliflozin Reduces Renal Hyperfiltration in Response to Uninephrectomy, but Is Not Nephroprotective in UNx/DOCA/Salt Mouse Models
Authors: Tauber Philipp , Sinha Frederick , Berger Raffaela S. , Gronwald Wolfram , Dettmer Katja , Kuhn Michaela , Trum Maximilian , Maier Lars S. , Wagner Stefan , Schweda Frank
Published: December 2021

Large-scale clinical outcome studies demonstrated the efficacy of SGLT2 inhibitors in patients with type II diabetes. Besides their therapeutic efficacy in diabetes, significant renoprotection was observed in non-diabetic patients with chronic kidney disease (CKD), suggesting the existence of glucose-independent beneficial effects of SGLT2 inhibitors. However, the relevant mechanisms by which SGLT2 inhibition delays the progression of renal injury are still largely unknown and speculative. Previous studies showed that SGLT2 inhibitors reduce diabetic hyperfiltration, which is likely a key element in renoprotection. In line with this hypothesis, this study aimed to investigate the nephroprotective effects of the SGLT2 inhibitor empagliflozin (EMPA) in different mouse models with non-diabetic hyperfiltration and progressing CKD to identify the underlying diabetes-independent cellular mechanisms. Non-diabetic hyperfiltration was induced by unilateral nephrectomy (UNx). Since UNx alone does not result in renal damage, renal disease models with varying degrees of glomerular damage and albuminuria were generated by combining UNx with high NaCl diets ± deoxycorticosterone acetate (DOCA) in different mouse strains with and without genetic predisposition for glomerular injury. Renal parameters (GFR, albuminuria, urine volume) were monitored for 4–6 weeks. Application of EMPA via the drinking water resulted in sufficient EMPA plasma concentration and caused glucosuria, diuresis and in some models renal hypertrophy. EMPA had no effect on GFR in untreated wildtype animals, but significantly reduced hyperfiltration after UNx by 36%. In contrast, EMPA did not reduce UNx induced hyperfiltration in any of our kidney disease models, regardless of their degree of glomerular damage caused by DOCA/salt treatment. Consistent with the lack of reduction in glomerular hyperfiltration, EMPA-treated animals developed albuminuria and renal fibrosis to a similar extent as H2O control animals. Taken together, the data clearly indicate that blockade of SGLT2 has the potential to reduce non-diabetic hyperfiltration in otherwise untreated mice. However, no effects on hyperfiltration or progression of renal injury were observed in hypervolemic kidney disease models, suggesting that high salt intake and extracellular volume might attenuate the protective effects of SGLT2 blockers.
Current Drug Repurposing Strategies for Rare Neurodegenerative Disorders
Authors: Shah Sweta , Dooms Marc Marie , Amaral-Garcia Sofia , Igoillo-Esteve Mariana
Published: December 2021

Rare diseases are life-threatening or chronically debilitating low-prevalent disorders caused by pathogenic mutations or particular environmental insults. Due to their high complexity and low frequency, important gaps still exist in their prevention, diagnosis, and treatment. Since new drug discovery is a very costly and time-consuming process, leading pharmaceutical companies show relatively low interest in orphan drug research and development due to the high cost of investments compared to the low market return of the product. Drug repurposing–based approaches appear then as cost- and time-saving strategies for the development of therapeutic opportunities for rare diseases. In this article, we discuss the scientific, regulatory, and economic aspects of the development of repurposed drugs for the treatment of rare neurodegenerative disorders with a particular focus on Huntington’s disease, Friedreich’s ataxia, Wolfram syndrome, and amyotrophic lateral sclerosis. The role of academia, pharmaceutical companies, patient associations, and foundations in the identification of candidate compounds and their preclinical and clinical evaluation will also be discussed.
A Microphysiological Cell-Culturing System for Pharmacokinetic Drug Exposure and High-Resolution Imaging of Arrays of 3D Microtissues
Authors: Lohasz Christian , Loretan Jacqueline , Sterker Dario , Görlach Ekkehard , Renggli Kasper , Argast Paul , Frey Olivier , Wiesmann Marion , Wartmann Markus , Rausch Martin , Hierlemann Andreas
Published: December 2021

Understanding the pharmacokinetic/pharmacodynamic (PK/PD)-relationship of a drug candidate is key to determine effective, yet safe treatment regimens for patients. However, current testing strategies are inefficient in characterizing in vivo responses to fluctuating drug concentrations during multi-day treatment cycles. Methods based on animal models are resource-intensive and require time, while traditional in vitro cell-culturing methods usually do not provide temporally-resolved information on the effects of in vivo–like drug exposure scenarios. To address this issue, we developed a microfluidic system to 1) culture arrays of three-dimensional spheroids in vitro, to 2) apply specific dynamic drug exposure profiles, and to 3) in-situ analyze spheroid growth and the invoked drug effects in 3D by means of 2-photon microscopy at tissue and single-cell level. Spheroids of fluorescently-labeled T-47D breast cancer cells were monitored under perfusion-culture conditions at short time intervals over three days and exposed to either three 24 h-PK-cycles or a dose-matched constant concentration of the phosphatidylinositol 3-kinase inhibitor BYL719. While the overall efficacy of the two treatment regimens was similar, spheroids exposed to the PK profile displayed cycle-dependent oscillations between regression and regrowth. Spheroids treated with a constant BYL719 concentration regressed at a steady, albeit slower rate. At a single-cell level, the cell density in BYL719-treated spheroids oscillated in a concentration-dependent manner. Our system represents a versatile tool for in-depth preclinical characterization of PK/PD parameters, as it enables an evaluation of drug efficacy and/or toxicity under realistic exposure conditions.
Live Cancer Cell Classification Based on Quantitative Phase Spatial Fluctuations and Deep Learning With a Small Training Set
Authors: Rotman-Nativ Noa , Shaked Natan T.
Published: December 2021

We present an analysis method that can automatically classify live cancer cells from cell lines based on a small data set of quantitative phase imaging data without cell staining. The method includes spatial image analysis to extract the cell phase spatial fluctuation map, derived from the quantitative phase map of the cell measured without cell labeling, thus without prior knowledge on the biomarker. The spatial fluctuations are indicative of the cell stiffness, where cancer cells change their stiffness as cancer progresses. In this paper, the quantitative phase spatial fluctuations are used as the basis for a deep-learning classifier for evaluating the cell metastatic potential. The spatial fluctuation analysis performed on the quantitative phase profiles before inputting them to the neural network was proven to increase the classification results in comparison to inputting the quantitative phase profiles directly, as done so far. We classified between primary and metastatic cancer cells and obtained 92.5% accuracy, in spite of using a small training set, demonstrating the method potential for objective automatic clinical diagnosis of cancer cells in vitro.
A Review of Cold Atmospheric Pressure Plasmas for Trauma and Acute Care
Authors: Garner Allen L. , Mehlhorn Thomas A.
Published: December 2021

Despite the high overall survival rates of severely injured military and civilian personnel requiring trauma and acute care, the challenges of treating infections and healing-resistant wounds have grown. Exposure to unknown environmental pathogens at the wound, including parasites and antibiotic resistant microorganisms, hinders timely and effective treatment using traditional techniques. Cold atmospheric pressure plasma (CAPP) provides a promising biophysical tool to address these issues by applying physically created modalities that cannot be circumvented by bioresistance to inactivate microorganisms and enhance wound healing. CAPPs generate charged particles and numerous reactive oxygen species (ROS) and reactive nitrogen species (RNS) that act on biological cells and tissues, often through plasma membrane interactions. This review fills a gap in the plasma medicine literature by specifically focusing on applying CAPPs for acute trauma, such as surgery, wound treatment, and disinfection. After briefly highlighting the areas of opportunity for improving acute trauma treatment and the fundamentals of CAPP generation, this review details emerging applications of CAPPs for enhanced wound healing, burn treatment, transdermal delivery, and surgical applications. We also discuss CAPP optimization through novel device design and synergistic combination with traditional treatment technologies to transition this biophysical technology to the battlefield and acute care settings.
Recent Progress and Development Trend of Self-Sweeping Fiber Laser
Authors: Zuo Zhenzhong , Wang Kaile , Chen Haowei , Lu Baole , Bai Jintao
Published: December 2021

Since 2011, when Kir’yanov et al. first reported a new wavelength self-sweeping ytterbium-doped fiber laser that does not rely on any tuning element but only on the dynamic induced grating generated in the gain fiber by the standing wave resonator structure, the self-sweeping effect based on fiber waveguides has been extensively studied, leading to great progress in fundamental physics and other applications of self-sweeping fiber lasers. Different doped fiber lasers have not only achieved the self-sweeping effect, but also observed new phenomena such as anomalous self-sweeping and continuous pulses. Due to their remarkable spectral and pulsed characteristics, self-sweeping fiber lasers have been widely used in spectral detection, fiber sensing and short pulse synthesis. In this paper, we will introduce the classification of different doped self-sweeping fiber lasers, summarize their different implementations, and introduce their self-sweeping laws, pulse characteristics, recent progress of applications and future development prospects.
Monitoring Expired CO2 Kinetics to Individualize Lung-Protective Ventilation in Patients With the Acute Respiratory Distress Syndrome
Authors: Suárez-Sipmann Fernando , Villar Jesús , Ferrando Carlos , Sánchez-Giralt Juan A. , Tusman Gerardo
Published: December 2021

Mechanical ventilation (MV) is a lifesaving supportive intervention in the management of acute respiratory distress syndrome (ARDS), buying time while the primary precipitating cause is being corrected. However, MV can contribute to a worsening of the primary lung injury, known as ventilation-induced lung injury (VILI), which could have an important impact on outcome. The ARDS lung is characterized by diffuse and heterogeneous lung damage and is particularly prone to suffer the consequences of an excessive mechanical stress imposed by higher airway pressures and volumes during MV. Of major concern is cyclic overdistension, affecting those lung segments receiving a proportionally higher tidal volume in an overall reduced lung volume. Theoretically, healthier lung regions are submitted to a larger stress and cyclic deformation and thus at high risk for developing VILI. Clinicians have difficulties in detecting VILI, particularly cyclic overdistension at the bedside, since routine monitoring of gas exchange and lung mechanics are relatively insensitive to this mechanism of VILI. Expired CO2 kinetics integrates relevant pathophysiological information of high interest for monitoring. CO2 is produced by cell metabolism in large daily quantities. After diffusing to tissue capillaries, CO2 is transported first by the venous and then by pulmonary circulation to the lung. Thereafter diffusing from capillaries to lung alveoli, it is finally convectively transported by lung ventilation for its elimination to the atmosphere. Modern readily clinically available sensor technology integrates information related to pulmonary ventilation, perfusion, and gas exchange from the single analysis of expired CO2 kinetics measured at the airway opening. Current volumetric capnography (VCap), the representation of the volume of expired CO2 in one single breath, informs about pulmonary perfusion, end-expiratory lung volume, dead space, and pulmonary ventilation inhomogeneities, all intimately related to cyclic overdistension during MV. Additionally, the recently described capnodynamic method provides the possibility to continuously measure the end-expiratory lung volume and effective pulmonary blood flow. All this information is accessed non-invasively and breath-by-breath helping clinicians to personalize ventilatory settings at the bedside and minimize overdistension and cyclic deformation of lung tissue.
Evolution of NLR Resistance Genes in Magnoliids: Dramatic Expansions of CNLs and Multiple Losses of TNLs
Authors: Wu Jia-Yi , Xue Jia-Yu , Van de Peer Yves
Published: December 2021

Magnoliids are the third-largest group of angiosperms and occupy a critical position in angiosperm evolution. In the past years, due to the lack of sequenced genomes, the disease resistance gene (R gene) profile of magnoliids remains poorly understood. By the genome-wide identification of 1,832 NLR genes from seven magnoliid genomes, we built a framework for the evolution of magnoliid R genes. TNL genes were completely absent from five magnoliids, presumably due to immune pathway deficiencies. A total of 74 ancestral R genes (70 CNLs, 3 TNLs, and 1 RNL) were recovered in a common ancestor of magnoliids, from which all current NLR gene repertoires were derived. Tandem duplication served as the major drive for NLR genes expansion in seven magnoliid genomes, as most surveyed angiosperms. Due to recent rapid expansions, most magnoliids exhibited “a first expansion followed by a slight contraction and a further stronger expansion” evolutionary pattern, while both Litsea cubeba and Persea americana showed a two-times-repeated pattern of “expansion followed by contraction.” The transcriptome analysis of seven different tissues of Saururus chinensis revealed a low expression of most NLR genes, with some R genes displaying a relatively higher expression in roots and fruits. Overall, our study sheds light on the evolution of NLR genes in magnoliids, compensates for insufficiency in major angiosperm lineages, and provides an important reference for a better understanding of angiosperm NLR genes.
Enhanced Flavonoid Accumulation Reduces Combined Salt and Heat Stress Through Regulation of Transcriptional and Hormonal Mechanisms
Authors: Jan Rahmatullah , Kim Nari , Lee Seo-Ho , Khan Muhammad Aaqil , Asaf Sajjad , Lubna  , Park Jae-Ryoung , Asif Saleem , Lee In-Jung , Kim Kyung-Min
Published: December 2021

Abiotic stresses, such as salt and heat stress, coexist in some regions of the world and can have a significant impact on agricultural plant biomass and production. Rice is a valuable crop that is susceptible to salt and high temperatures. Here, we studied the role of flavanol 3-hydroxylase in response to combined salt and heat stress with the aim of better understanding the defensive mechanism of rice. We found that, compared with wild-type plants, the growth and development of transgenic plants were improved due to higher biosynthesis of kaempferol and quercetin. Furthermore, we observed that oxidative stress was decreased in transgenic plants compared with that in wild-type plants due to the reactive oxygen species scavenging activity of kaempferol and quercetin as well as the modulation of glutathione peroxidase and lipid peroxidase activity. The expression of high-affinity potassium transporter (HKT) and salt overly sensitive (SOS) genes was significantly increased in transgenic plants compared with in control plants after 12 and 24 h, whereas sodium-hydrogen exchanger (NHX) gene expression was significantly reduced in transgenic plants compared with in control plants. The expression of heat stress transcription factors (HSFs) and heat shock proteins (HSPs) in the transgenic line increased significantly after 6 and 12 h, although our understanding of the mechanisms by which the F3H gene regulates HKT, SOS, NHX, HSF, and HSP genes is limited. In addition, transgenic plants showed higher levels of abscisic acid (ABA) and lower levels of salicylic acid (SA) than were found in control plants. However, antagonistic cross talk was identified between these hormones when the duration of stress increased; SA accumulation increased, whereas ABA levels decreased. Although transgenic lines showed significantly increased Na+ ion accumulation, K+ ion accumulation was similar in transgenic and control plants, suggesting that increased flavonoid accumulation is crucial for balancing Na+/K+ ions. Overall, this study suggests that flavonoid accumulation increases the tolerance of rice plants to combined salt and heat stress by regulating physiological, biochemical, and molecular mechanisms.
CottonGVD: A Comprehensive Genomic Variation Database for Cultivated Cottons
Authors: Peng Zhen , Li Hongge , Sun Gaofei , Dai Panhong , Geng Xiaoli , Wang Xiao , Zhang Xiaomeng , Wang Zhengzhen , Jia Yinhua , Pan Zhaoe , Chen Baojun , Du Xiongming , He Shoupu
Published: December 2021

Cultivated cottons are the most important economic crop, which produce natural fiber for the textile industry. In recent years, the genetic basis of several essential traits for cultivated cottons has been gradually elucidated by decoding their genomic variations. Although an abundance of resequencing data is available in public, there is still a lack of a comprehensive tool to exhibit the results of genomic variations and genome-wide association study (GWAS). To assist cotton researchers in utilizing these data efficiently and conveniently, we constructed the cotton genomic variation database (CottonGVD; http://120.78.174.209/ or http://db.cngb.org/cottonGVD). This database contains the published genomic information of three cultivated cotton species, the corresponding population variations (SNP and InDel markers), and the visualized results of GWAS for major traits. Various built-in genomic tools help users retrieve, browse, and query the variations conveniently. The database also provides interactive maps (e.g., Manhattan map, scatter plot, heatmap, and linkage disequilibrium block) to exhibit GWAS and expression GWAS results. Cotton researchers could easily focus on phenotype-associated loci visualization, and they are interested in and screen for candidate genes. Moreover, CottonGVD will continue to update by adding more data and functions.
A Flute, Musical Bows and Bamboo Clarinets that “Speak” in the Amazon Rainforest; Speech and Music in the Gavião Language of Rondônia
Authors: Meyer Julien , Moore Denny
Published: December 2021

The Gavião, a native Amazonian group in Rondônia, Brazil, use three different traditional musical instruments that they identify as “speaking” ones and that are characterized by a very tight music-lyric relation through similar pitch patterns: a flute (called kotiráp), a pair of mouth bows (iridináp), and three large bamboo clarinets (totoráp), played by three different players, each one playing a single-note clarinet. They show in different ways the relation of acoustic iconicity which exists between the words of the songs’ lyrics and the music played on such instruments to “sing” the songs. Linguistic analysis makes it possible to understand the phonetic and phonological nature of the iconicity. The sung speech form, being intermediate between the spoken and the instrumental forms, is useful for both learning and explaining the musical notes. In a language with distinctive tone and length, such as Gavião of Rondônia, the first question about speech that is played by musical instruments is the relation between the melodies and the supersegmental phonology of the corresponding words in sung speech and in modal spoken speech. It is influenced by the phonological possibilities of the spoken form and by the musical possibilities of the instrumental form. The description and analysis of Gavião instrumental speech and song practices are found to be a noteworthy contribution to the typology of instrumental language surrogates associated with a tone language, one that calls for a reexamination of hypotheses about which aspects of the phonological/phonetic structure can be transposed in instrumental speech and how this can be done. The role of this kind of instrumental sung speech is artistic and also practical as it contributes to maintain the oral heritage. Such practice represents a little-studied and threatened cultural heritage of the traditional substratum of the cultures of Amazonia.
The Role of EFL Teachers’ Praise and Love in Preventing Students’ Hopelessness
Authors: Liu Fengzhen
Published: December 2021

The emotional dimension of language teaching and learning has recently gained momentum among researchers after pioneering works in positive psychology. Now, teachers’ and students’ emotions play an important role in learning process. Despite the growing body of research on many psychological constructs in L2 education, the role of teacher praise and love in precluding students’ sense of hopelessness about their future and efforts has been largely ignored. Addressing such problems, the present study aimed to examine the definitions, conceptualizations, influencing factors, causes, and outcomes of these three psychological variables in EFL contexts. Moreover, to position the study, this article took a quick glance at the affective trend in education referring to positive outcomes of a loving pedagogy. Finally, different practical implications, research gaps, and future lines of research were provided for passionate researchers.
Music Therapy vs. Music Listening for Negative Symptoms in Schizophrenia: Randomized, Controlled, Assessor- and Patient-Blinded Trial
Authors: Pedersen Inge Nygaard , Bonde Lars Ole , Hannibal Niels Jørgensen , Nielsen Jimmi , Aagaard Jørgen , Gold Christian , Rye Bertelsen Lars , Jensen Silvia Beatriz , Nielsen René Ernst
Published: December 2021

Objective: To investigate the efficacy of music therapy for negative symptoms in patients with schizophrenia.

Methods: Randomized, participant- and assessor-blinded, multicenter, controlled trial including patients diagnosed with schizophrenia according to ICD-10 with predominantly negative symptoms, between 18 and 65 years. Participants were randomized to 25 successive weekly individual sessions (excluding holidays, including cancellation by the participant) of either music therapy conducted by trained music therapists, or music listening together with a social care worker. The primary outcome was reduction in negative symptoms as measured by The Positive and negative Syndrome Scale (PANSS) negative subscale total score, assessed by a blinded rater, utilizing mixed-effects model analysis.

Results: In total, 57 participants were randomized; 39 completed the study's initial 15 weeks, and 30 completed follow-up at 25 weeks. On the primary outcome of PANSS negative subscale, no significant difference was observed between groups with a coefficient of −0.24 (95% CI −1.76 to 1.27, P = 0.754) in the intention to treat analysis, and −0.98 (95% CI −5.06 to 3.09, P = 0.625) when only analyzing completers. Both interventions showed significant reduction from baseline to 25 weeks on PANSS negative subscale. On secondary outcomes, no between group differences were observed in The Brief Negative Symptom Scale, WHOQOL-Bref (Quality of Life), The Helping Alliance Questionnaire and The Global Assessment of Functioning in the intention to treat or completers populations utilizing Mixed Effects Models.

Conclusion: No difference between groups randomized to music therapy vs. musical listening was observed resulting in no clear recommendation for which intervention to use as the first choice for treatment of patients diagnosed with schizophrenia and predominantly having negative symptoms.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT02942459.
Development of an Online Resource for People Bereaved by Suicide: A Mixed-Method User-Centered Study Protocol
Authors: Leaune Edouard , Lestienne Laurène , Grandgenèvre Pierre , Morgiève Margot , Vaiva Guillaume , Vieux Maxime , Chalancon Benoît , Laplace Nathalie , Haesebaert Julie , Poulet Emmanuel
Published: December 2021

Introduction: Suicide bereavement is known to be highly distressing and is frequently associated with mental health problems. Despite high-level of need regarding mental and physical health, people bereaved by suicide display low level of help-seeking and perceived support in the aftermath of the loss. The lack of accessibility and reliability of face-to-face counseling resources is notably reported by suicide survivors. Online resources can enhance early access to help and support for people bereaved by suicide. The primary objective of the study is to design and implement an innovative and adaptive online resource for people bereaved by suicide according to their needs and expectation regarding online solutions dedicated to suicide bereavement.

Methods: The ESPOIR2S study is a mixed-method user-centered study. ESPOIR2S seeks to build the resource from the perspectives and needs of both people bereaved by suicide and professionals or volunteers working in the field of postvention. The Information System Research (ISR) Framework is used to guide the design of the study through a 3-step research cycle. The structure of the ESPOIR2S study relies on a simultaneous collection of qualitative and quantitative data which will be collected and analyzed during (a) the Relevance cycle through an online questionnaire and focus groups; (b) the Design cycle through focus groups; and (c) and the Rigor cycle through an online questionnaire and semi-structured interviews. The user-centeredness will be ensured by the active participation of people bereaved by suicide, members of associations for bereaved people and professionals of postvention.

Discussion: The mixed-method and user-centered design of the ESPOIR2S study will offer an in-depth collection of the needs and expectation of suicide survivors regarding online resources. Through the implementation of an adaptive online solution, we aim to enhance the access to help and support for suicide survivors which are highly correlated with well-being and recovery.
Look After Yourself: Students Consistently Showing High Resilience Engaged in More Self-Care and Proved More Resilient During the COVID-19 Pandemic
Authors: Meine Laura E. , Strömer Eike , Schönfelder Sandra , Eckhardt Eliza I. , Bergmann Anna K. , Wessa Michèle
Published: December 2021

The COVID-19 pandemic has prompted severe restrictions on everyday life to curb the spread of infections. For example, teaching at universities has been switched to an online format, reducing students' opportunities for exchange, and social interaction. Consequently, their self-reported mental health has significantly decreased and there is a pressing need to elucidate the underlying mechanisms—ideally considering not only data collected during the pandemic, but also before. One hundred seventeen German university students aged 18-27 were assessed for known resilience factors (optimism, self-care, social support, generalized self-efficacy) and subsequently completed surveys on stress experiences and mental health every 3 months over a period of 9 months before the outbreak of the pandemic and once during the first lockdown in Germany. For each timepoint before the pandemic, we regressed participants' mental health against the reported stressor load, such that the resulting residuals denote better or worse than expected outcomes, i.e., the degree of resilient functioning. We then tested whether different expressions in the resilience factors were predictive of distinct resilient functioning trajectories, which were identified through latent class growth analysis. Finally, we investigated whether trajectory class, resilience factors, and perceived stress predicted resilience during the pandemic. Results show rather stable resilient functioning trajectories, with classes differing mainly according to degree rather than change over time. More self-care was associated with a higher resilient functioning trajectory, which in turn was linked with the most favorable pandemic response (i.e., lower perceived stress and more self-care). Although findings should be interpreted with caution given the rather small sample size, they represent a rare examination of established resilience factors in relation to resilience over an extended period and highlight the relevance of self-care in coping with real-life stressors such as the pandemic.
Audience-Dependent Explanations for AI-Based Risk Management Tools: A Survey
Authors: Hadji Misheva Branka , Jaggi David , Posth Jan-Alexander , Gramespacher Thomas , Osterrieder Joerg
Published: December 2021

Artificial Intelligence (AI) is one of the most sought-after innovations in the financial industry. However, with its growing popularity, there also is the call for AI-based models to be understandable and transparent. However, understandably explaining the inner mechanism of the algorithms and their interpretation is entirely audience-dependent. The established literature fails to match the increasing number of explainable AI (XAI) methods with the different stakeholders’ explainability needs. This study addresses this gap by exploring how various stakeholders within the Swiss financial industry view explainability in their respective contexts. Based on a series of interviews with practitioners within the financial industry, we provide an in-depth review and discussion of their view on the potential and limitation of current XAI techniques needed to address the different requirements for explanations.
Virtual Energy Management for Physical Energy Savings in a Legged Robot Hopping on Granular Media
Authors: Roberts Sonia F. , Koditschek Daniel E.
Published: December 2021

We discuss an active damping controller to reduce the energetic cost of a single step or jump of dynamic locomotion without changing the morphology of the robot. The active damping controller adds virtual damping to a virtual leg spring created by direct-drive motors through the robot’s leg linkage. The virtual damping added is proportional to the intrusion velocity of the robot’s foot, slowing the foot’s intrusion, and thus the rate at which energy is transferred to and dissipated by the ground. In this work, we use a combination of simulations and physical experiments in a controlled granular media bed with a single-leg robot to show that the active damping controller reduces the cost of transport compared with a naive compression-extension controller under various conditions.
Drone Surveying of Volumetric Ice Growth in a Steep River
Authors: Rødtang Einar , Alfredsen Knut , Juárez Ana
Published: December 2021

Representative ice thickness data is essential for accurate hydraulic modelling, assessing the potential for ice induced floods, understanding environmental conditions during winter and estimation of ice-run forces. Steep rivers exhibit complex freeze-up behaviour combining formation of columnar ice with successions of anchor ice dams to build a complete ice cover, resulting in an ice cover with complex geometry. For such ice covers traditional single point measurements are unrepresentative. Gathering sufficiently distributed measurements for representativeness is labour intensive and at times impossible with hard to access ice. Structure from Motion (SfM) software and low-cost drones have enabled river ice mapping without the need to directly access the ice, thereby reducing both the workload and the potential danger in accessing the ice. In this paper we show how drone-based photography can be used to efficiently survey river ice and how these photographic surveys can be processed into digital elevation models (DEMs) using Structure from Motion. We also show how DEMs of the riverbed, riverbanks and ice conditions can be used to deduce ice volume and ice thickness distributions. A QGIS plugin has been implemented to automate these tasks. These techniques are demonstrated with a survey of a stretch of the river Sokna in Trøndelag, Norway. The survey was carried out during the winter 2020–2021 at various stages of freeze-up using a simple quadcopter with camera. The 500 m stretch of river studied was estimated to have an ice volume of up to 8.6 × 103 m3 (This corresponds to an average ice thickness of ∼67 cm) during the full ice cover condition of which up to 7.2 × 103 m3 (This corresponds to an average ice thickness of ∼57 cm) could be anchor ice. Ground Control Points were measured with an RTK-GPS and used to determine that the accuracy of these ice surface geometry measurements lie between 0.03 and 0.09 m. The ice thicknesses estimated through the SfM methods are on average 18 cm thicker than the manual measurements. Primarily due to the SfM methods inability to detect suspended ice covers. This paper highlights the need to develop better ways of estimating the volume of air beneath suspended ice covers.