bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of Life and Role of Palliative and Supportive Care for Patients With Brain Metastases and Caregivers: A Review
Authors: Wu Adela , Colón Gabriela Ruiz , Lim Michael
Published: February 2022

Brain metastases (BM) are the most commonly diagnosed secondary brain lesions in adults, influencing these patients' symptoms and treatment courses. With improvements in oncologic treatments, patients with BM are now living longer with their advanced cancers, and issues pertaining to quality of life become more pressing. The American Society of Clinical Oncology has recommended early implementation of palliative care for cancer patients, though incorporation and implementation of palliative and other supportive services in the setting of true multidisciplinary care requires additional attention and research for patients with intracranial metastases. We review the physical, cognitive, and psychosocial challenges patients with BM and their caregivers face during their cancer course as well as the current published research on quality of life metrics relating to this patient population and the diverse roles specialty palliative care, rehabilitation services, and other healthcare providers play in a comprehensive multidisciplinary care model.
Mouse Nerve Growth Factor Injection and Progression Rate in Patients With Amyotrophic Lateral Sclerosis: An Observational Study
Authors: Li Jia-Tong , Dong Si-Qi , Qian Ting , Yang Wen-Bo , Chen Xiang-Jun
Published: February 2022

Objectives

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease with no curative treatment up to now. This study aims to analyze ALS progression of patients treated with mouse nerve growth factor (mNGF), as well as the effects, side effects, and adverse events of the therapy.

Materials and Methods

A retrospective, observational study was performed including 94 patients with ALS from July 2020 to July 2021. Thirty-two of them were treated with at least one course of mNGF on a regular riluzole use, and the rest 62 were treated with riluzole only. The declining rates of body mass index (BMI) and ALS Functional Rating Scale-Revised (ALSFRS-R) scores were compared between the two groups to indicate ALS progression.

Results

No significant differences in ALS progression indicated by the declining rates of BMI and ALSFRS-R score were observed between the two cohorts. ALS progression before and after the first treatment course of mNGF also showed no discernible difference. However, we noticed a moderate 62.7 and 25.1% reduction in the declining rate of BMI and ALSFRS-R motor subscore when comparing mNGF + riluzole treatment to riluzole only. The mNGF treatment was overall safe and well-tolerated, and a rare case of diarrhea was reported after mNGF injection.

Conclusions

Our study revealed that mNGF treatment was overall safe and well-tolerated in patients of ALS. Application of mNGF combined with regular riluzole treatment had no significant clinical effects on delaying ALS progression. Prospective cohort studies and randomized clinical trials based on larger cohorts and longer follow-up times are needed to make a more convincing conclusion.
Predicting the Need for Desmopressin Treatment During Inpatient and After Discharge Following Endoscopic Sellar Surgery
Authors: Wong Chia-En , Wang Wei-Hsin , Lan Ming-Ying , Lee Po-Hsuan , Huang Chi-Chen , Su Pei-Fang , Lee Jung-Shun
Published: February 2022

Introduction

Postoperative diabetes insipidus (DI) is a common complication following endoscopic sellar surgery. However, the requirement of desmopressin treatment for patients with DI are heterogenous. Although the predictors of postoperative DI have been reported, whether these patients required desmopressin treatment remained uninvestigated. Predicting the need of desmopressin can benefit clinical decision making more directly than predicting the occurence of postoperative DI. This study aimed to identify variables that predict the need for desmopressin treatment following sellar surgery.

Methods

Patients undergoing endoscopic sellar surgery between 2016 and 2019 were retrospectively reviewed. Twenty-three variables, characterized as potential predictors for requiring desmopressin treatment, were analyzed. To assess the capability to generalize the identified predictors, external validation with receiver operating characteristic (ROC) analysis was performed using a second series from 2019 to 2020.

Results

Postoperative DI occurred in 40 of 159 included patients. Twelve patients required inpatient desmopressin treatment and 20 patients needed desmopressin prescription after discharge. The potential predictors of requiring any desmopressin use included higher peak sodium (Na) level (p = 0.007), lower minimum Na level (p = 0.043), and higher peak urine output (p = 0.006), but these were not supported by external validation. The predictors of requiring desmopressin after discharge included higher peak Na (p = 0.040) and minimum Na levels (p = 0.048), which were supported by external ROC validation showing areas under curve of 0.787, 0.611, and 0.898 for peak Na (p = 0.036), minimum Na (p = 0.460), and peak Na – minimum Na levels (p < 0.001), respectively. A criterion of peak Na ≥ 150 mmol/L or peak Na – minimum Na ≥ 10 predicted the need of desmopressin prescription after discharge. A postoperative management algorithm was proposed.

Conclusion

The required treatments for patients with postoperative DI following endoscopic sellar surgery are heterogenous. Elevated peak Na and large peak Na—minimum Na levels in the perioperative period predicted requiring desmopressin after hospital discharge. Patients with peak Na <150 mmol/L and peak Na—minimum Na <10 can be safely discharged without desmopressin prescription.
Halo Sport Transcranial Direct Current Stimulation Improved Muscular Endurance Performance and Neuromuscular Efficiency During an Isometric Submaximal Fatiguing Elbow Flexion Task
Authors: Wang Lejun , Wang Ce , Yang Hua , Shao Qineng , Niu Wenxin , Yang Ye , Zheng Fanhui
Published: February 2022

The present study examined the effects of transcranial direct current stimulation (tDCS) using Halo Sport on the time to exhaustion (TTE) in relation with muscle activities and corticomuscular coupling of agonist and antagonist muscles during a sustained isometric fatiguing contraction performed with the elbow flexors. Twenty healthy male college students were randomly assigned to tDCS group and control group. The two group participants performed two experimental sessions which consisted of pre-fatigue isometric maximal voluntary contraction (MVC), sustained submaximal voluntary contractions (30% maximal torque) performed to exhaustion, and post-fatigue MVC with the right elbow flexor muscles. Sham stimulation (90 s) and tDCS (20 min) were applied for control and tDCS group participants 20 min prior to the second session test, respectively. MVC strength in pre- and post-fatigue test, TTE, electroencephalogram (EEG), and electromyography (EMG) of biceps brachii (BB) and triceps brachii (TB) were recorded during the tests. It was found that tDCS using the Halo Sport device significantly increased TTE and thus improved muscular endurance performance. The improvement may be partly related to the improvement of neuromuscular efficiency as reflected by decrease of antagonistic muscle coactivation activities, which may be related to cortical originated central processing mechanism of neuromuscular activities.
Olfactory Stimulation and the Diagnosis of Patients With Disorders of Consciousness: A Double-Blind, Randomized Clinical Trial
Authors: Wang Jing , Zhang Shaoming , Liu Wenbin , Zhang Yao , Hu Zhouyao , Sun Ziwei , Di Haibo
Published: February 2022

Objectives

The aim of this study was to determine whether behavioral responses elicited by olfactory stimulation are a predictor of conscious behavioral response and prognosis of patients with disorders of consciousness (DOC).

Methods

Twenty-three DOC patients (8 unresponsive wakefulness syndrome [UWS]; 15 minimally conscious state [MCS]) were recruited for this study in which 1-Octen-3-ol (familiar neutral odor) and pyridine were used to test odor behavioral responses, and water was used as an odorless stimulus. One rater presented the three odors in front of each patient’s nose randomly, and another one videotaped all behavioral responses (e.g., pouting, wrinkling nose, slightly shaking head, frowning, etc.). Two independent raters, blind to the stimuli and the patient’s diagnosis, gave the behavioral results according to the recorded videos. One-, 3-, and 6-month follow-up evaluations were conducted to obtain a good prognostic value.

Results

All MCS patients showed behavioral responses to the 1-Octen-3-ol stimulus; nine MCS and one UWS showed olfactory emotional responses to the pyridine, and two MCS showed olfactory emotional responses to the water stimulus. The incidence of behavioral response was significantly higher using 1-Octen-3-ol than it was for water by McNemar test (p < 0.001), significantly higher using pyridine than it was for water (p < 0.01). The χ2 test results indicated that there were significant differences between MCS and UWS to 1-Octen-3-ol (p < 0.001). For MCS patients, the incidence of behavioral response was no different between using 1-Octen-3-ol and pyridine (p > 0.05). There was no significant relationship between the olfactory behavioral response and the improvement of consciousness based on the χ2 test analysis (p > 0.05).

Conclusion

Olfactory stimuli, especially for the familiar neutral odor, might be effective for eliciting a conscious behavioral response and estimating the clinical diagnosis of DOC patients.

Clinical Trial Registration

[https://clinicaltrials.gov/ct2/show/NCT03732092], [identifier NCT03732092].
Intracranial Aneurysm Rupture Risk Estimation With Multidimensional Feature Fusion
Authors: An Xingwei , He Jiaqian , Di Yang , Wang Miao , Luo Bin , Huang Ying , Ming Dong
Published: February 2022

The rupture of aneurysms is the main cause of spontaneous subarachnoid hemorrhage (SAH), which is a serious life-threatening disease with high mortality and permanent disability rates. Therefore, it is highly desirable to evaluate the rupture risk of aneurysms. In this study, we proposed a novel semiautomatic prediction model for the rupture risk estimation of aneurysms based on the CADA dataset, including 108 datasets with 125 annotated aneurysms. The model consisted of multidimensional feature fusion, feature selection, and the construction of classification methods. For the multidimensional feature fusion, we extracted four kinds of features and combined them into the feature set, including morphological features, radiomics features, clinical features, and deep learning features. Specifically, we applied the feature extractor 3D EfficientNet-B0 to extract and analyze the classification capabilities of three different deep learning features, namely, no-sigmoid features, sigmoid features, and binarization features. In the experiment, we constructed five distinct classification models, among which the k-nearest neighbor classifier showed the best performance for aneurysm rupture risk estimation, reaching an F2-score of 0.789. Our results suggest that the full use of multidimensional feature fusion can improve the performance of aneurysm rupture risk assessment. Compared with other methods, our method achieves the state-of-the-art performance for aneurysm rupture risk assessment methods based on CADA 2020.
The Effect of Non-invasive Spinal Cord Stimulation on Anorectal Function in Individuals With Spinal Cord Injury: A Case Series
Authors: Kreydin Evgeniy , Zhong Hui , Lavrov Igor , Edgerton V. Reggie , Gad Parag
Published: February 2022

Spinal cord injury (SCI) is a devastating condition that impacts multiple organ systems. Neurogenic bowel dysfunction (NBD) frequently occurs after a SCI leading to reduced sensation of bowel fullness and bowel movement often leading to constipation or fecal incontinence. Spinal Neuromodulation has been proven to be a successful modality to improve sensorimotor and autonomic function in patients with spinal cord injuries. The pilot data presented here represents the first demonstration of using spinal neuromodulation to activate the anorectal regions of patients with spinal cord injuries and the acute and chronic effects of stimulation. We observed that spinal stimulation induces contractions as well as changes in sensation and pressure profiles along the length of the anorectal region. In addition, we present a case report of a patient with a SCI and the beneficial effect of spinal neuromodulation on the patient’s bowel program.
Voluntary Exercise Prevents Hypertensive Response Sensitization Induced by Angiotensin II
Authors: Xue Baojian , Cui Jun-Ling , Guo Fang , Beltz Terry G. , Zhao Zi-Gang , Zhang Geng-Shen , Johnson Alan Kim
Published: February 2022

Exercise training has profound effects on the renin-angiotensin system, inflammatory cytokines and oxidative stress, all of which affect autonomic nervous system activity and regulate blood pressure (BP) in both physiological and pathophysiological states. Using the Induction-Delay-Expression paradigm, our previous studies demonstrated that various challenges (stressors) during Induction resulted in hypertensive response sensitization (HTRS) during Expression. The present study tested whether voluntary exercise would protect against subpressor angiotensin (ANG) II-induced HTRS in rats. Adult male rats were given access to either “blocked” (sedentary rats) or functional running (exercise rats) wheels for 12 weeks, and the Induction-Delay-Expression paradigm was applied for the rats during the last 4 weeks. A subpressor dose of ANG II given during Induction produced an enhanced hypertensive response to a pressor dose of ANG II given during Expression in sedentary rats in comparison to sedentary animals that received saline (vehicle control) during Induction. Voluntary exercise did not attenuate the pressor dose of ANG II-induced hypertension but prevented the expression of HTRS seen in sedentary animals. Moreover, voluntary exercise reduced body weight gain and feed efficiency, abolished the augmented BP reduction after ganglionic blockade, reversed the increased mRNA expression of pro-hypertensive components, and upregulated mRNA expression of antihypertensive components in the lamina terminalis and hypothalamic paraventricular nucleus, two key brain nuclei involved in the control of sympathetic activity and BP regulation. These results indicate that exercise training plays a beneficial role in preventing HTRS and that this is associated with shifting the balance of the brain prohypertensive and antihypertensive pathways in favor of attenuated central activity driving sympathetic outflow and reduced BP.
Parvalbumin Role in Epilepsy and Psychiatric Comorbidities: From Mechanism to Intervention
Authors: Godoy Lívea Dornela , Prizon Tamiris , Rossignoli Matheus Teixeira , Leite João Pereira , Liberato José Luiz
Published: February 2022

Parvalbumin is a calcium-binding protein present in inhibitory interneurons that play an essential role in regulating many physiological processes, such as intracellular signaling and synaptic transmission. Changes in parvalbumin expression are deeply related to epilepsy, which is considered one of the most disabling neuropathologies. Epilepsy is a complex multi-factor group of disorders characterized by periods of hypersynchronous activity and hyperexcitability within brain networks. In this scenario, inhibitory neurotransmission dysfunction in modulating excitatory transmission related to the loss of subsets of parvalbumin-expressing inhibitory interneuron may have a prominent role in disrupted excitability. Some studies also reported that parvalbumin-positive interneurons altered function might contribute to psychiatric comorbidities associated with epilepsy, such as depression, anxiety, and psychosis. Understanding the epileptogenic process and comorbidities associated with epilepsy have significantly advanced through preclinical and clinical investigation. In this review, evidence from parvalbumin altered function in epilepsy and associated psychiatric comorbidities were explored with a translational perspective. Some advances in potential therapeutic interventions are highlighted, from current antiepileptic and neuroprotective drugs to cutting edge modulation of parvalbumin subpopulations using optogenetics, designer receptors exclusively activated by designer drugs (DREADD) techniques, transcranial magnetic stimulation, genome engineering, and cell grafting. Creating new perspectives on mechanisms and therapeutic strategies is valuable for understanding the pathophysiology of epilepsy and its psychiatric comorbidities and improving efficiency in clinical intervention.
Deep Learning With Radiomics for Disease Diagnosis and Treatment: Challenges and Potential
Authors: Zhang Xingping , Zhang Yanchun , Zhang Guijuan , Qiu Xingting , Tan Wenjun , Yin Xiaoxia , Liao Liefa
Published: February 2022

The high-throughput extraction of quantitative imaging features from medical images for the purpose of radiomic analysis, i.e., radiomics in a broad sense, is a rapidly developing and emerging research field that has been attracting increasing interest, particularly in multimodality and multi-omics studies. In this context, the quantitative analysis of multidimensional data plays an essential role in assessing the spatio-temporal characteristics of different tissues and organs and their microenvironment. Herein, recent developments in this method, including manually defined features, data acquisition and preprocessing, lesion segmentation, feature extraction, feature selection and dimension reduction, statistical analysis, and model construction, are reviewed. In addition, deep learning-based techniques for automatic segmentation and radiomic analysis are being analyzed to address limitations such as rigorous workflow, manual/semi-automatic lesion annotation, and inadequate feature criteria, and multicenter validation. Furthermore, a summary of the current state-of-the-art applications of this technology in disease diagnosis, treatment response, and prognosis prediction from the perspective of radiology images, multimodality images, histopathology images, and three-dimensional dose distribution data, particularly in oncology, is presented. The potential and value of radiomics in diagnostic and therapeutic strategies are also further analyzed, and for the first time, the advances and challenges associated with dosiomics in radiotherapy are summarized, highlighting the latest progress in radiomics. Finally, a robust framework for radiomic analysis is presented and challenges and recommendations for future development are discussed, including but not limited to the factors that affect model stability (medical big data and multitype data and expert knowledge in medical), limitations of data-driven processes (reproducibility and interpretability of studies, different treatment alternatives for various institutions, and prospective researches and clinical trials), and thoughts on future directions (the capability to achieve clinical applications and open platform for radiomics analysis).
CD38: A Significant Regulator of Macrophage Function
Authors: Li Wentao , Li Yanling , Jin Xi , Liao Qianjin , Chen Zhifang , Peng Honghua , Zhou Yanhong
Published: February 2022

Cluster of differentiation 38 (CD38) is a cell surface glycoprotein and multifunctional extracellular enzyme. As a NADase, CD38 produces adenosine through the adenosine energy pathway to cause immunosuppression. As a cell surface receptor, CD38 is necessary for immune cell activation and proliferation. The aggregation and polarization of macrophages are affected by the knockout of CD38. Intracellular NAD+ levels are reduced by nuclear receptor liver X receptor-alpha (LXR) agonists in a CD38-dependent manner, thereby reducing the infection of macrophages. Previous studies suggested that CD38 plays an important role in the regulation of macrophage function. Therefore, as a new marker of macrophages, the effect of CD38 on macrophage proliferation, polarization and function; its possible mechanism; the relationship between the expression level of CD38 on macrophage surfaces and disease diagnosis, treatment, etc; and the role of targeting CD38 in macrophage-related diseases are reviewed in this paper to provide a theoretical basis for a comprehensive understanding of the relationship between CD38 and macrophages.
ω-3 and ω-6 Polyunsaturated Fatty Acids Regulate the Proliferation, Invasion and Angiogenesis of Gastric Cancer Through COX/PGE Signaling Pathway
Authors: Ma Jiachi , Zhang Chensong , Liang Wanqing , Li Lei , Du Jun , Pan Chengwu , Chen Bangling , Chen Yuzhong , Wang Yuanpeng
Published: February 2022

Background

This study aims to investigate the effects of ω-3, ω-6 polyunsaturated fatty acids (PUFAs), and their middle metabolites prostaglandin (PGE)2 and PGE3 on proliferation, invasion, and angiogenesis formation of gastric cancer cells and to explore associated mechanism.

Methods

RT-PCR and ELISA were used to detect the expression of cyclooxygenase (COX)-1 and COX-2 in gastric cancer cell lines. The effect of ω-3, ω-6, PGE2, and PGE3 on the proliferation, invasion, and angiogenesis of gastric cancer cells were measured by cell proliferation, invasion, and angiogenesis assay in vitro. COX-2 small interfering RNA (siRNA) was transfected into gastric cancer cells, and the expression of COX-2 protein was detected by Western blot. COX-2 gene silencing influencing proliferation, invasion, and angiogenesis potential of gastric cancer cells was detected by WST-1, transwell chamber, and angiogenesis assay, respectively.

Results

COX-2 was only expressed in MKN74 and MKN45 cells. In gastric cancer cell lines with positive COX-2 expression, ω-6 and PGE2 could significantly enhance the proliferation, invasion, and angiogenesis of gastric cancer cells, and after transfection with COX-2 siRNA, the effects of ω-6 and PGE2 on enhancing the proliferation, invasion, and angiogenesis of gastric cancer cells were significantly attenuated; ω-3 and PEG3 could inhibit the proliferation, invasion, and angiogenesis of gastric cancer cells. In gastric cancer cell lines with negative COX-2 expression, ω-6 and PGE2 had no significant effect on the proliferation, invasion, and angiogenesis of gastric cancer; ω-3 and PGE3 could significantly inhibit the proliferation, invasion, and angiogenesis of gastric cancer.

Conclusion

ω-6 PUFAs reinforce the metastatic potential of gastric cancer cells via COX-2/PGE2; ω-3 PUFAs inhibit the metastatic potential of gastric cancer via COX-1/PGE3 signaling axis.
Case Report: Benefits of a NSCLC Patient With EGFR A289G/F287_G288insHA cis Mutations From Immunotherapy in Combination With Antiangiogenesis and Chemotherapy and Sequential Treatment of EGFR-TKI
Authors: Zhang He , Dong Weiwei , Zhao Huixia , Hu Yanyan , You Xia , Sun Tingting , Xiao Wenhua
Published: February 2022

We presented a 67-year-old nonsmoking female lung adenocarcinoma patient with novel epidermal growth factor receptor (EGFR) A289G/F287_G288insHA cis mutations who responded positively to sintilimab combined with regorafenib and albumin paclitaxel, and sequential treatment of icotinib. Gene mutations in patients were detected by next-generation sequencing (NGS) technology, and changes in gene mutations before and after treatments were observed by ctDNA monitoring. We observed the efficacy of the patient through chest computed tomography (CT) imaging and carcinoembryonic antigen (CEA) level and found that the patient benefited from immunotherapy in combination with antiangiogenesis and chemotherapy for more than 1 year, CEA levels initially fell sharply and then rebounded during the treatment period. After changing to EGFR-TKI therapy, the CEA level of the patient does not only decreased sharply at the initial stage of treatment but also rebounded and increased at the later stage of treatment. The patient was tested for genetic mutations after 4 months of sequential EGFR-TKI therapy and was found to have lost all previous EGFR mutations, which may be the cause of resistance to targeted drug icotinib. We believe that our findings have enriched the EGFR mutation spectrum in NSCLC and highlighted the possible choice for patients harboring this mutation by immunotherapy combined with chemotherapy and antivascular therapy, and EGFR-TKI-targeted therapy.
Ruptured Hepatocellular Carcinoma: Current Status of Research
Authors: Xia Feng , Ndhlovu Elijah , Zhang Mingyu , Chen Xiaoping , Zhang Bixiang , Zhu Peng
Published: February 2022

Background

Ruptured hepatocellular carcinoma (rHCC) is considered a rare and life-threatening manifestation; when it happens, it often requires acute and positive intervention. At present, the mechanism of rHCC development is gradually being understood while there are many kinds of rHCC treatment. From our clinical observation, the prognosis of rHCC patients is not as poor as it is currently believed. It may not be appropriate to include all patients with rHCC in T4.

Main Body

The incidence of ruptured hepatocellular carcinoma is now rising. Especially in the Asian region, it can even reach 10% – 15%. The most common symptom of HCC rupture is abdominal pain, and there are now a variety of treatments for hepatocellular carcinoma rupture. With aggressive treatment, rHCC patients can also achieve a better prognosis. The patient’s condition varies on admission, so the treatment methods will also be different. It is critical to identify prognostic factors simultaneously, and rHCC can be effectively managed by focusing on important prognostic factors.

Conclusion

A review was carried out to analyze diagnosis, mechanism, treatment, and prognostic risk factors on this disease condition during the current situation; it is hoped that it will provide better guidance for clinicians. Moreover, patients with rHCC were managed hierarchically to prolong their prognosis.
Molecular Characterization and Gene Expression Analysis of Aquaporin in Haemaphysalis qinghaiensis
Authors: Niu Qingli , Hao Rongzeng , Pan Yuping , Liu Zhijie , Yang Jifei , Guan Guiquan , Luo Jianxun , Yin Hong
Published: February 2022

Aquaporins (AQPs) are important functional proteins and are widely present in the cell membrane of almost all organisms, mediating transmembrane transport of liquid and other solutes. Much is known about the molecular characterization of AQPs in other tick species; however, nothing is known about them in Haemaphysalis qinghaiensis. In this study, we first sequenced the transcript variants of AQPs in H. qinghaiensis (HqAQPs), analyzed the biological structure features of AQPs, and investigated the pattern of gene expression of the AQP gene of H. qinghaiensis in different tick tissues and stages to predict their biological functions. In conclusion, four AQP transcript variants (i.e., HqAQP1-1, HqAQP1-2, HqAQP1-3, and HqAQP1-4) of H. qinghaiensis were found, and the sequences were comparable with its orthologs from the reported tick species. Gene expression of AQPs in different tick tissues and stages showed the higher expression level in salivary glands and gut of adult female, as well as in the female and nymph than in Malpighian tubules, ovary, male, larvae, and egg. Further studies will be performed to evaluate the function of HqAQPs against H. qinghaiensis infestation on animals.
Phenylephrine-Induced Cardiovascular Changes in the Anesthetized Mouse: An Integrated Assessment of in vivo Hemodynamics Under Conditions of Controlled Heart Rate
Authors: Rajanathan Rajkumar , Pedersen Tina Myhre , Thomsen Morten B. , Botker Hans Erik , Matchkov Vladimir V.
Published: February 2022

Objective

Investigating the cardiovascular system is challenging due to its complex regulation by humoral and neuronal factors. Despite this complexity, many existing research methods are limited to the assessment of a few parameters leading to an incomplete characterization of cardiovascular function. Thus, we aim to establish a murinein vivomodel for integrated assessment of the cardiovascular system under conditions of controlled heart rate. Utilizing this model, we assessed blood pressure, cardiac output, stroke volume, total peripheral resistance, and electrocardiogram (ECG).

Hypothesis

We hypothesize that (i) ourin vivomodel can be utilized to investigate cardiac and vascular responses to pharmacological intervention with the α1-agonist phenylephrine, and (ii) we can study cardiovascular function during artificial pacing of the heart, modulating cardiac function without a direct vascular effect.

Methods

We included 12 mice that were randomly assigned to either vehicle or phenylephrine intervention through intraperitoneal administration. Mice were anesthetized with isoflurane and intubated endotracheally for mechanical ventilation. We measured blood pressureviaa solid-state catheter in the aortic arch, blood flowviaa probe on the ascending aorta, and ECG from needle electrodes on the extremities. Right atrium was electrically paced at a frequency ranging from 10 to 11.3 Hz before and after either vehicle or phenylephrine administration.

Results

Phenylephrine significantly increased blood pressure, stroke volume, and total peripheral resistance compared to the vehicle group. Moreover, heart rate was significantly decreased following phenylephrine administration. Pacing significantly decreased stroke volume and cardiac output both prior to and after drug administration. However, phenylephrine-induced changes in blood pressure and total peripheral resistance were maintained with increasing pacing frequencies compared to the vehicle group. Total peripheral resistance was not significantly altered with increasing pacing frequencies suggesting that the effect of phenylephrine is primarily of vascular origin.

Conclusion

In conclusion, thisin vivomurine model is capable of distinguishing between changes in peripheral vascular and cardiac functions. This study underlines the primary effect of phenylephrine on vascular function with secondary changes to cardiac function. Hence, thisin vivomodel is useful for the integrated assessment of the cardiovascular system.
Computational Systems Biology of Alfalfa – Bacterial Blight Host-Pathogen Interactions: Uncovering the Complex Molecular Networks for Developing Durable Disease Resistant Crop
Authors: Kataria Raghav , Duhan Naveen , Kaundal Rakesh
Published: February 2022

Medicago sativa(also known as alfalfa), a forage legume, is widely cultivated due to its high yield and high-value hay crop production. Infectious diseases are a major threat to the crops, owing to huge economic losses to the agriculture industry, worldwide. The protein-protein interactions (PPIs) between the pathogens and their hosts play a critical role in understanding the molecular basis of pathogenesis.Pseudomonas syringaepv.syringaeALF3 suppresses the plant’s innate immune response by secreting type III effector proteins into the host cell, causing bacterial stem blight in alfalfa. The alfalfa-P. syringaesystem has little information available for PPIs. Thus, to understand the infection mechanism, we elucidated the genome-scale host-pathogen interactions (HPIs) between alfalfa andP. syringaeusing two computational approaches: interolog-based and domain-based method. A total of ∼14 M putative PPIs were predicted between 50,629 alfalfa proteins and 2,932P. syringaeproteins by combining these approaches. Additionally, ∼0.7 M consensus PPIs were also predicted. The functional analysis revealed thatP. syringaeproteins are highly involved in nucleotide binding activity (GO:0000166), intracellular organelle (GO:0043229), and translation (GO:0006412) while alfalfa proteins are involved in cellular response to chemical stimulus (GO:0070887), oxidoreductase activity (GO:0016614), and Golgi apparatus (GO:0005794). According to subcellular localization predictions, most of the pathogen proteins targeted host proteins within the cytoplasm and nucleus. In addition, we discovered a slew of new virulence effectors in the predicted HPIs. The current research describes an integrated approach for deciphering genome-scale host-pathogen PPIs between alfalfa andP. syringae, allowing the researchers to better understand the pathogen’s infection mechanism and develop pathogen-resistant lines.
Genetic Dissection and Quantitative Trait Loci Mapping of Agronomic and Fodder Quality Traits in Sorghum Under Different Water Regimes
Authors: Somegowda Vinutha K. , Prasad Kodukula V. S. V. , Naravula Jalaja , Vemula Anilkumar , Selvanayagam Sivasubramani , Rathore Abhishek , Jones Chris S. , Gupta Rajeev , Deshpande Santosh P.
Published: February 2022

Livestock provides an additional source of income for marginal cropping farmers, but crop residues that are used as a main source of animal feed are characteristically low in digestibility and protein content. This reduces the potential livestock product yield and quality. The key trait, which influences the quality and the cost of animal feed, is digestibility. In this study, we demonstrate that sorghum breeding can be directed to achieve genetic gains for both fodder biomass and digestibility without any trade-offs. The genotypic variance has shown significant differences for biomass across years (13,035 in 2016 and 3,395 in 2017) while in vitro organic matter digestibility (IVOMD) showed significant genotypic variation in 2016 (0.253) under drought. A range of agronomic and fodder quality traits was found to vary significantly in the population within both the control and drought conditions and across both years of the study. There was significant genotypic variance (σg2) and genotypic × treatment variance (σgxt2) in dry matter production in a recombinant inbred line (RIL) population in both study years, while there was only significant σg2 and σgxt2 in IVOMD under the control conditions. There was no significant correlation identified between biomass and digestibility traits under the control conditions, but there was a positive correlation under drought. However, a negative relation was observed between digestibility and grain yield under the control conditions, while there was no significant correlation under drought population, which was genotyped using the genotyping-by-sequencing (GBS) technique, and 1,141 informative single nucleotide polymorphism (SNP) markers were identified. A linkage map was constructed, and a total of 294 quantitative trait loci (QTLs) were detected, with 534 epistatic interactions, across all of the traits under study. QTL for the agronomic traits fresh and dry weight, together with plant height, mapped on to the linkage group (LG) 7, while QTL for IVOMD mapped on to LG1, 2, and 8. A number of genes previously reported to play a role in nitrogen metabolism and cell wall-related functions were found to be associated with these QTL.
Response of a Diverse European Soybean Collection to “Short Duration” and “Long Duration” Drought Stress
Authors: Saleem Aamir , Aper Jonas , Muylle Hilde , Borra-Serrano Irene , Quataert Paul , Lootens Peter , De Swaef Tom , Roldán-Ruiz Isabel
Published: February 2022

Drought causes significant damage to a high value crop of soybean. Europe has an increasing demand for soybean and its own production is insufficient. Selection and breeding of cultivars adapted to European growth conditions is therefore urgently needed. These new cultivars must have a shorter growing cycle (specifically for adaptation to North-West Europe), high yield potential under European growing conditions, and sufficient drought resistance. We have evaluated the performance of a diverse collection of 359 soybean accessions under drought stress using rain-out shelters for 2 years. The contrasting weather conditions between years and correspondingly the varying plant responses demonstrated that the consequences of drought for an individual accession can vary strongly depending on the characteristics (e.g., duration and intensity) of the drought period. Short duration drought stress, for a period of four to 7 weeks, caused an average reduction of 11% in maximum canopy height (CH), a reduction of 17% in seed number per plant (SN) and a reduction of 16% in seed weight per plant (SW). Long duration drought stress caused an average reduction of 29% in CH, a reduction of 38% in SN and a reduction of 43% in SW. Drought accelerated plant development and caused an earlier cessation of flowering and pod formation. This seemed to help some accessions to better protect the seed yield, under short duration drought stress. Drought resistance for yield-related traits was associated with the maintenance of growth under long duration drought stress. The collection displayed a broad range of variation for canopy wilting and leaf senescence but a very narrow range of variation for crop water stress index (CWSI; derived from canopy temperature data). To the best of our knowledge this is the first study reporting a detailed investigation of the response to drought within a diverse soybean collection relevant for breeding in Europe.
Map-Based Cloning and Characterization of Br-dyp1, a Gene Conferring Dark Yellow Petal Color Trait in Chinese Cabbage (Brassica rapa L. ssp. pekinensis)
Authors: Yang Shuangjuan , Liu Honglei , Zhao Yanyan , Su Henan , Wei Xiaochun , Wang Zhiyong , Zhao Xiaobin , Zhang Xiao-Wei , Yuan Yuxiang
Published: February 2022

Flower color is an important trait in Brassica species. However, genes responsible for the dark yellow flower trait in Chinese cabbage have not been reported. In this study, we identified a dark-yellow-flowered Chinese cabbage line SD369. Genetic analysis indicated that the dark yellow flower trait in SD369 was controlled by a single recessive locus, Br-dyp1 (dark yellow petal color 1 in Brassica rapa). Using bulked segregant RNA sequencing and kompetitive allele-specific PCR assays, Br-dyp1 was fine-mapped to an interval of 53.6 kb on chromosome A09. Functional annotation analysis, expression analysis, and sequence variation analysis revealed that Bra037130 (BraA09.ZEP), which encodes a zeaxanthin epoxidase, was the most likely candidate gene for Br-dyp1. Carotenoid profile analysis suggested that Bra037130 (BraA09.ZEP) might participate in the epoxidation from zeaxanthin to violaxanthin. The 679 bp insertion in dark yellow petal caused premature stop codon, thus caused the loss-of-function of the enzyme zeaxanthin epoxidase (ZEP), which disturbed the carotenoid metabolism, and caused the increased accumulation of total carotenoid, and finally converted the flower color from yellow to dark yellow. Comparative transcriptome analysis also showed that the “carotenoid biosynthesis” pathway was significantly enriched, and genes involved in carotenoid degradation and abscisic acid biosynthesis and metabolism were significantly downregulated. Furthermore, we developed and validated the functional marker Br-dyp1-InDel for Br-dyp1. Overall, these results provide insight into the molecular basis of carotenoid-based flower coloration in B. rapa and reveal valuable information for marker-assisted selection breeding in Chinese cabbage.
Semantic Contingency of Maternal Verbal Input Directed at Very Preterm and Full-Term Children
Authors: Salerni Nicoletta , Suttora Chiara
Published: February 2022

Several studies have testified to the importance of a responsive linguistic input for children’s language acquisition and development. In particular, maternal use of expansions, imitations, interpretations, and labels has been shown to promote both children’s language comprehension and production. From this perspective, the present study examined the semantically contingent linguistic input addressed to very preterm children’s comparing it to that directed to full-term children observed during a semi-structured play session when the children were 24 months of age. The relationships between maternal contingent utterances and children’s communicative repertoires were also investigated. The main results showed that mothers of full-term children produced a higher proportion of semantically contingent utterances than those of very preterm children; moreover, this variable was associated with children’s more advanced communicative-linguistic outcomes. Overall, this study supports the interdependence between mothers’ use of certain linguistic strategies and children’s communicative-linguistic repertoire, extending this evidence to children born very preterm and suggesting the importance of considering the semantic contingency aspect of child-directed speech to support the communicative and linguistic development of these children.
Comparing the Relative Importance of Predictors of Intention to Use Bicycles
Authors: Baeli Valentina , Hichy Zira , Sciacca Federica , De Pasquale Concetta
Published: February 2022

The use of bicycles for active commuting is an important target to reach because of the importance of increasing physical activity among the population and improving the air quality in cities. Among the models that have been utilized in previous studies, the Theory of Planned Behavior (TPB) has shown good results in terms of the total variance obtained. However, establishing the relative importance of the TPB variables is difficult. In the present study, which was carried out in the Italian context, the authors sought to establish the weight of the proposed variables based on the dominance analysis approach. Considering the initiatives, which the Italian government carries out, and the particular period in which the study was developed, the authors included two variables in addition to the classical factors: financial incentives and daily commuting habits. A survey was administered to 294 Italians (222 females and 72 males, from 18 to 77 years old) through social networks from July to September 2020. The results have shown how the main predictor of bicycle use was use habits, followed almost at the same level by financial incentives and attitude, while norms and perceived behavioral control (PBC) present low relative importance among the variables considered. Limits of the study have been discussed, and suggestions for future research have been proposed.
Navigating Exploitative and Explorative Leadership in Support of Infrastructure Resilience
Authors: Helmrich Alysha , Chester Mikhail
Published: February 2022

Leadership is a critical component in approaching infrastructure resilience. Leadership, the formal and informal governance within an organization, drives an infrastructure system's ability to respond to changing circumstances. Due to the instability of the Anthropocene, infrastructure managers (individuals who design, build, maintain, and decommission infrastructure) can no longer rely on assumptions of stationarity, but instead that shifts are occurring at a faster rate than institutions and infrastructure organizations are adapting. Leadership and organizational change literature provide considerable insights into the ability of organizations to navigate uncertainty and complexity, and infrastructure organizations may be able to learn from this knowledge to avoid obsolescence. Therefore, this article asks: what leadership capabilities do infrastructure organizations need to readily respond to stability and instability? An integrative leadership framework is proposed, exploring capabilities of collaboration, perception and exploration toward learning, and flexible informal and formal governance leveraged by leadership. These capabilities are driven by underlying tensions (e.g., climate change, emerging technologies) and managed through enabling leadership, a set of processes for pivoting between stability and instability. The framework is then applied to infrastructure organizations. Lack of market competition may make infrastructure organizations more open to collaboration and, therefore, learning. However, the need to provide specific services may cause risk adversity and an avoidance of failure, restricting flexibility and innovation. It is critical for infrastructure organizations to identify their strengths and weaknesses so they may develop an approach to change at pace with their external environments.
Affecting Effects on Affect: The Impact of Protocol Permutations on Affective Responses to Sprint Interval Exercise; A Systematic Review and Meta-Analysis of Pooled Individual Participant Data
Authors: Metcalfe Richard S. , Williams Sean , Fernandes Gwen S. , Astorino Todd A. , Stork Matthew J. , Phillips Shaun M. , Niven Ailsa , Vollaard Niels B. J.
Published: February 2022

Responses to sprint interval exercise (SIE) are hypothesized to be perceived as unpleasant, but SIE protocols are diverse, and moderating effects of various SIE protocol parameters on affective responses are unknown. We performed a systematic search to identify studies (up to 01/05/2021) measuring affective valence using the Feeling Scale during acute SIE in healthy adults. Thirteen studies involving 18 unique trials and 316 unique participant (142 women and 174 men) affective responses to SIE were eligible for inclusion. We received individual participant data for all participants from all studies. All available end-of-sprint affect scores from each trial were combined in a linear mixed model with sprint duration, mode, intensity, recovery duration, familiarization and baseline affect included as covariates. Affective valence decreased significantly and proportionally with each additional sprint repetition, but this effect was modified by sprint duration: affect decreased more during 30 s (0.84 units/sprint; 95% CI: 0.74–0.93) and 15–20 s sprints (1.02 units/sprint; 95% CI: 0.93–1.10) compared with 5–6 s sprints (0.20 units/sprint; 95% CI: 0.18–0.22) (both p < 0.0001). Although the difference between 15–20 s and 30 s sprints was also significant (p = 0.02), the effect size was trivial (d = −0.12). We observed significant but trivial effects of mode, sprint intensity and pre-trial familiarization, whilst there was no significant effect of recovery duration. We conclude that affective valence declines during SIE, but the magnitude of the decrease for an overall SIE session strongly depends on the number and duration of sprints. This information can be applied by researchers to design SIE protocols that are less likely to be perceived as unpleasant in studies of real-world effectiveness.

Systematic Review Registration

Open Science Framework, https://osf.io/sbyn3.