bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Phenotypes of Tumors Invading the Rectosigmoid Colon Affecting the Extent of Debulking Surgery and Survival in Advanced Ovarian Cancer
Authors: Park Soo Jin , Mun Jaehee , Lee Eun Ji , Park Sunwoo , Kim Sang Youn , Lim Whasun , Song Gwonhwa , Kim Jae-Weon , Lee Seungmee , Kim Hee Seung
Published: April 2021

We classified clinical phenotypes based on tumor separability from the rectosigmoid colon and then evaluated the effect of these clinical phenotypes on surgical outcomes and prognosis of advanced ovarian cancer. We collected data of patients with stage IIIB-IVB disease who either underwent visceral segmental serosectomy (VSS) or low anterior resection (LAR) during maximal debulking surgery. All patients were divided into the following, according to the resection types of tumors involving the rectosigmoid colon: the focal (tumor-involved length <18 cm) and separable (FS) group that received VSS, the focal and inseparable (FI) that received LAR, or the diffuse (tumor-involved length ≥18 cm) group (D) that also received LAR. A total of 83 patients were included in FS (n=44, 53%), FI (n=18, 21.7%), and D (n=24, 25.3%) groups. FS and D groups with more extensive tumors were related to wider extent of surgery and more tumor infiltration except for bowels, whereas FI and D groups with more invasive tumors were associated with wider extent of surgery, more tumor infiltration to bowels, longer operation time, more blood loss, more transfusion, longer hospitalization, and higher surgical complexity scores. Moreover, FS and FI groups showed better progression-free survival than D group, whereas FS group demonstrated better overall survival than FI and D groups. Clinical phenotypes based on tumor separability from the rectosigmoid colon may depend on tumor invasiveness and extensiveness in advanced ovarian cancer. Moreover, these clinical phenotypes may affect surgical outcomes and survival.
Characteristics of Pan-Cancer Patients With Ultrahigh Tumor Mutation Burden
Authors: Yuan Hong , Ji Jun , Shi Min , Shi Yan , Liu Jing , Wu Junwei , Yang Chen , Xi Wenqi , Li Qingyuan , Zhu Wei , Li Jingjie , Gong Xiaoli , Zhang Jun
Published: April 2021

Background

Tumor mutation burden has been proven to be a good predictor for the efficacy of immunotherapy, especially in patients with hypermutation. However, most research focused on the analysis of hypermutation in individual tumors, and there is a lack of integrated research on the hypermutation across different cancers. This study aimed to characterize hypermutated patients to distinguish between these patients and non-hypermutated patients.

Methods

A total of 5,980 tumor samples involving 23 types of solid tumors from the in-house database were included in the study. Based on the cutoff value of tumor mutation burden (TMB), all samples were divided into hypermutated or non-hypermutated groups. Microsatellite instability status, PD-L1 expression and other mutation-related indicators were analyzed.

Results

Among the 5,980 tumor samples, 1,164 were selected as samples with hypermutation. Compared with the non-hypermutated group, a significant increase in the mutation rates of DNA mismatch repair genes and polymerase genes was detected in the hypermutated group, and there was an overlap between high TMB and high microsatellite instability or high PD-L1. In addition, we found that EGFR, KRAS and PIK3CA had a high frequency of both single nucleotide variation and copy number variation mutations. These identified mutant genes were enriched in the oncogenic signaling pathway and the DNA damage repair pathway. At the same time, the somatic cell characteristics and distribution of the two groups were significantly different.

Conclusions

This study identified genetic and phenotypic characteristics of hypermutated tumors and demonstrated that DNA damage repair is critically involved in hypermutation.
Clinical Characteristics and Prognostic Factors of Children With Anti-N-Methyl-D-Aspartate Receptor Encephalitis
Authors: Yang Sai , Yang Liming , Liao Hongmei , Chen Mei , Feng Mei , Liu Shulei , Tan Lihong
Published: April 2021

Objective: Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is the most common autoimmune encephalitis in pediatric patients. The study aimed to investigate the clinical characteristics and prognostic factors of anti-NMDA receptor encephalitis in children in South China.

Methods: This was a retrospective study of children diagnosed with anti-NMDA receptor encephalitis between 01/2014 and 12/2017 at Hunan Children's Hospital. Laboratory, brain magnetic resonance imaging (MRI), and electroencephalography data were collected. The short-term (6-month) outcomes were assessed using the Liverpool score by the same pediatric neurologist. The children were divided into good (scores 4–5) and poor (score <3) clinical outcomes.

Results: Among the 51 patients, 21 (41.2%) were male. The most common clinical symptoms were dyskinesia (88.2%), personality change (84.3%), seizure (82.4%), and cognitive disorder (31.4%). Two were transferred to another hospital, 45 (91.8%) received intravenous immunoglobulins, 41 (83.7%) received methylprednisolone, and 8 (16.3%) received plasma exchange. Eight (16.3%) received rituximab for second-line treatment, six after intravenous immunoglobulin and methylprednisolone treatment, and two after plasma exchange therapy failed. Seven were lost to follow-up. The short-term outcome was good in 23 patients. Cognitive disorder [odds ratio (OR): 23.97, 95% confidence interval (CI): 1.12–513.30, P = 0.042) and abnormal brain MRI (OR: 14.29, 95% CI: 1.36–150.10, P = 0.027] were independently associated with a poor short-term outcome after adjustment for age, GCS, and rituximab use.

Conclusions: MRI abnormalities and cognitive disorders are independently associated with poor short-term outcomes in children with anti-NMDA receptor encephalitis. The use of rituximab is not associated with the 6-month outcomes.
Case Report: A Case of Eyelid Myoclonic Status With Tonic–Clonic Seizure and Literature Review
Authors: Yuan Yujun , Yang Fenghua , Huo Liang , Fan Yuying , Liu Xueyan , Wu Qiong , Wang Hua
Published: April 2021

Eyelid myoclonus with or without absence epilepsy is a rare and usually misdiagnosed disease in the neurology department. It is an idiopathic general epileptic syndrome, the onset period is 6–8 years, and is more common in girls. It is characterized by rapid abnormal eye blinking, accompanied by upward rolling of the eye and slight backward movement of the head, with eye closure sensitivity and photosensitivity. The seizure is frequent and short, dozens or even hundreds of times a day; a small number of patients may have eyelid myoclonus status. We report a patient who visits the hospital for the first time with eyelid myoclonic problem; the patient continued to wink the eyes, eye rolled up, and backward movement of the head, accompanied by impairment of consciousness. Video electroencephalography (VEEG) suggests continued spike slow-wave, polyspike slow-wave. After the patient had 2, 4, 6, 8, 10, 12, and 14 Hz of intermittent photic stimulation (IPS), her seizures and epileptic discharges reduced or stopped. Seven min after giving stimulation at 20 Hz, the child developed an occipital-initiated tonic–clonic seizure, which demonstrated that after sufficient IPS stimulation, the occiput cortex became excited and initiated a brain network, leading to diffuse brain discharge and tonic–clonic seizures. At 1 h after onset, the child developed a nonconvulsive state, with impairment of consciousness despite no eyelid myoclonic movements, and VEEG suggested a large number of epileptic discharges. After 10 min of administrating midazolam, the patient's EEG immediately became normal, and the patient regained consciousness. Therefore, this paper presents an eyelid myoclonus status patient with occipital origin seizure, we recorded the whole course of the disease and the treatment effect, and reviewed the literature accordingly.
Robust Performance of Potentially Functional SNPs in Machine Learning Models for the Prediction of Atorvastatin-Induced Myalgia
Authors: Ooi Brandon N. S. , Raechell  , Ying Ariel F. , Koh Yong Zher , Jin Yu , Yee Sherman W. L. , Lee Justin H. S. , Chong Samuel S. , Tan Jack W. C. , Liu Jianjun , Lee Caroline G. , Drum Chester L.
Published: April 2021

Background:

Statins can cause muscle symptoms resulting in poor adherence to therapy and increased cardiovascular risk. We hypothesize that combinations of potentially functional SNPs (pfSNPs), rather than individual SNPs, better predict myalgia in patients on atorvastatin. This study assesses the value of potentially functional single nucleotide polymorphisms (pfSNPs) and employs six machine learning algorithms to identify the combination of SNPs that best predict myalgia.

Methods: Whole genome sequencing of 183 Chinese, Malay and Indian patients from Singapore was conducted to identify genetic variants associated with atorvastatin induced myalgia. To adjust for confounding factors, demographic and clinical characteristics were also examined for their association with myalgia. The top factor, sex, was then used as a covariate in the whole genome association analyses. Variants that were highly associated with myalgia from this and previous studies were extracted, assessed for potential functionality (pfSNPs) and incorporated into six machine learning models. Predictive performance of a combination of different models and inputs were compared using the average cross validation area under ROC curve (AUC). The minimum combination of SNPs to achieve maximum sensitivity and specificity as determined by AUC, that predict atorvastatin-induced myalgia in most, if not all the six machine learning models was determined.

Results: Through whole genome association analyses using sex as a covariate, a larger proportion of pfSNPs compared to non-pf SNPs were found to be highly associated with myalgia. Although none of the individual SNPs achieved genome wide significance in univariate analyses, machine learning models identified a combination of 15 SNPs that predict myalgia with good predictive performance (AUC >0.9). SNPs within genes identified in this study significantly outperformed SNPs within genes previously reported to be associated with myalgia. pfSNPs were found to be more robust in predicting myalgia, outperforming non-pf SNPs in the majority of machine learning models tested.

Conclusion: Combinations of pfSNPs that were consistently identified by different machine learning models to have high predictive performance have good potential to be clinically useful for predicting atorvastatin-induced myalgia once validated against an independent cohort of patients.
Ligustilide Prevents Radiation Enteritis by Targeting Gch1/BH4/eNOS to Improve Intestinal Ischemia
Authors: Yan Tao , Guo Shun , Zhang Tian , Zhang Zhimin , Liu An , Zhang Song , Xu Yuan , Qi Yuhong , Zhao Weihe , Wang Qinhui , Shi Lei , Liu Linna
Published: April 2021

There is a high incidence of radiation enteritis (RE) after abdominal radiotherapy. The occurrence of RE seriously affects the treatment and quality of life of patients; however, its pathogenesis is complex and there are no effective drugs for its prevention or treatment. Intestinal ischemia plays an important role in the occurrence of enteritis. Previous studies have shown that targeting GTP-cyclohydrolase 1 (Gch1) to improve intestinal ischemia could be a new strategy to prevent and treat RE. A high content of the naturally occurring phthalide derivative ligustilide (LIG) has been found in the plant drug Rhizoma Ligustici Chuanxiong for the treatment of cardiovascular diseases. The purpose of this study was to evaluate the protective effects of LIG on RE. Ionizing radiation (IR) rat and endothelial cell models were used to observe and record rat body weights and stool morphologies, measure intestinal blood perfusion by laser Doppler blood flow imaging, determine the diastolic functions of mesenteric arteries, detect the levels of Gch1/BH4/eNOS pathway-related proteins and regulatory molecules in the mesenteric arteries and endothelial cells, and predict affinity by molecular docking technology. The results showed that LIG significantly improved the body weights, loose stools, intestinal villi lengths, intestinal perfusion and vasodilatory functions of IR rats. LIG also significantly improved Gch1 protein and BH4 levels in the mesenteric arteries and endothelial cells after IR, increased the NO content, reduced superoxide accumulation, and improved p-eNOS (Ser1177) levels in endothelial cells. LIG has good affinity for Gch1, which significantly improves its activity. These results indicate that LIG is the preferred compound for the prevention and treatment of RE by improving intestinal ischemia through the Gch1/BH4/eNOS pathway. This study provides a theoretical basis and new research ideas for the development of new drugs for RE.
Isoliensinine: A Natural Compound with “Drug-Like” Potential
Authors: Cheng Yan , Li Hong-Li , Zhou Zi-Wei , Long Hui-Zhi , Luo Hong-Yu , Wen Dan-Dan , Cheng Lin , Gao Li-Chen
Published: April 2021

Isoliensinine, a bisbenzylisoquinoline alkaloid isolated from Nelumbo nucifera Gaertn, exerts a variety of beneficial effects, such as antitumor, cardioprotective, antioxidant, antidepressant, and anti-HIV effects, and ameliorates T2DM with hyperlipidemia and Alzheimer’s disease. In this article, the recent literature on isoliensinine, including its pharmacology, pharmacokinetics, and synthesis and extraction, is summarized. Moreover, possible future prospects and research directions are also discussed. Studies on isoliensinine were found by searching a combination of keywords including “pharmacology,” “pharmacokinetics,” and “synthesis and extraction” in the main databases, including PubMed, Google Scholar, Web of Science, NCBI, and Wan Fang. Many studies have pointed out that a major limitation of isoliensinine is its poor solubility in aqueous media. Considering its advantages and limitations, isoliensinine can be used as a lead compound to develop novel efficient and low-toxicity derivatives. The available literature indicates that isoliensinine displays “drug-like” potential. Additionally, there are many related issues and novel mechanisms that need to be explored.
SARS-CoV-2: Pathogenesis, Molecular Targets and Experimental Models
Authors: Kanimozhi G. , Pradhapsingh B. , Singh Pawar Charan , Khan Haseeb A. , Alrokayan Salman H. , Prasad N. Rajendra
Published: April 2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recent pandemic outbreak threatening human beings worldwide. This novel coronavirus disease-19 (COVID-19) infection causes severe morbidity and mortality and rapidly spreading across the countries. Therefore, there is an urgent need for basic fundamental research to understand the pathogenesis and druggable molecular targets of SARS-CoV-2. Recent sequencing data of the viral genome and X-ray crystallographic data of the viral proteins illustrate potential molecular targets that need to be investigated for structure-based drug design. Further, the SARS-CoV-2 viral pathogen isolated from clinical samples needs to be cultivated and titrated. All of these scenarios demand suitable laboratory experimental models. The experimental models should mimic the viral life cycle as it happens in the human lung epithelial cells. Recently, researchers employing primary human lung epithelial cells, intestinal epithelial cells, experimental cell lines like Vero cells, CaCo-2 cells, HEK-293, H1299, Calu-3 for understanding viral titer values. The human iPSC-derived lung organoids, small intestinal organoids, and blood vessel organoids increase interest among researchers to understand SARS-CoV-2 biology and treatment outcome. The SARS-CoV-2 enters the human lung epithelial cells using viral Spike (S1) protein and human angiotensin-converting enzyme 2 (ACE-2) receptor. The laboratory mouse show poor ACE-2 expression and thereby inefficient SARS-CoV-2 infection. Therefore, there was an urgent need to develop transgenic hACE-2 mouse models to understand antiviral agents’ therapeutic outcomes. This review highlighted the viral pathogenesis, potential druggable molecular targets, and suitable experimental models for basic fundamental research.
High Dose Intravenous Vitamin C for Preventing The Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched Before-After Study
Authors: Zhao Bing , Liu Min , Liu Ping , Peng Yibing , Huang Jun , Li Mengjiao , Wang Yihui , Xu LiLi , Sun Silei , Qi Xing , Ling Yun , Li Jian , Zhang Wenhong , Mao Enqiang , Qu Jieming
Published: April 2021

Background: Coronavirus disease 2019 (COVID-19) pandemic is continuing to impact multiple countries worldwide and effective treatment options are still being developed. In this study, we investigate the potential of high-dose intravenous vitamin C (HDIVC) in the prevention of moderate COVID-19 disease aggravation.

Methods: In this retrospective before-after case-matched clinical study, we compare the outcome and clinical courses of patients with moderate COVID-19 patients who were treated with an HDIVC protocol (intravenous injection of vitamin C, 100 mg/kg/day, 1 g/h, for 7 days from admission) during a one-month period (between March 18 and april 18, 2020, HDIVC group) with a control group treated without the HDIVC protocol during the preceding two months (January 18 to March 18, 2020). Patients in the two groups were matched in a 1:1 ratio according to age and gender.

Results: The HDIVC and control groups each comprised 55 patients. For the primary outcomes, there was a significant difference in the number of patients that evolved from moderate to severe type between the two groups (HDIVC: 4/55 vs. control: 12/55, relative risk [RR] = 0.28 [0.08, 0.93], P = 0.03). Compared to the control group, there was a shorter duration of systemic inflammatory response syndrome (SIRS) (P = 0.0004) during the first week and lower SIRS occurrence (2/21 vs 10/22, P = 0.0086) on Day 7 (6–7 days after admission). In addition, HDIVC group had lower C-reactive protein levels (P = 0.005) and higher number of CD4+ T cells from Day 0 (on admission) to Day 7 (P = 0.04).” The levels of coagulation indicators, including activated partial thromboplastin time and D-dimer were also improved in the HDIVC compared to the control group on Day 7.

Conclusion: HDIVC may be beneficial in limiting disease aggravation in the early stage of COVID-19 pneumonia, which may be related to its improvements on the inflammatory response, immune function and coagulation function. Further randomized controlled trials are required to augment these findings.
Cannabinoid Receptor Agonist Inhibits Atrial Electrical Remodeling in a Tachypaced Ex Vivo Rat Model
Authors: Lee Danielle I. , Murninkas Michael , Elyagon Sigal , Etzion Yoram , Anderson Hope D.
Published: April 2021

Introduction: Atrial fibrillation (AF) leads to rate-dependent atrial changes collectively defined as atrial remodelling (AR). Shortening of the atrial effective refractory period (AERP) and decreased conduction velocity are among the hallmarks of AR. Pharmacological strategies to inhibit AR, thereby reducing the self-perpetual nature of AF, are of great clinical value. Cannabinoid receptor (CBR) ligands may exert cardioprotective effects; CB13, a dual CBR agonist with limited brain penetration, protects cardiomyocytes from mitochondrial dysfunction induced by endothelin-1. Here, we examined the effects of CB13 on normal physiology of the rat heart and development of tachypacing-induced AR.

Methods: Rat hearts were perfused in a Langendorff set-up with CB13 (1 µM) or vehicle. Hemodynamic properties of non-paced hearts were examined conventionally. In a different set of hearts, programmed stimulation protocol was performed before and after atrial tachypacing for 90 min using a mini-hook platinum quadrupole electrode inserted on the right atrium. Atrial samples were further assessed by western blot analysis.

Results: CB13 had no effects on basal hemodynamic properties. However, the compound inhibited tachypacing-induced shortening of the AERP. Protein expression of PGC1α was significantly increased by CB13 compared to vehicle in paced and non-paced hearts. Phosphorylation of AMPKα at residue threonine 172 was increased suggesting upregulation of mitochondrial biogenesis. Connexin43 was downregulated by tachypacing. This effect was diminished in the presence of CB13.

Conclusion: Our findings support the notion that peripheral activation of CBR may be a new treatment strategy to prevent AR in patients suffering from AF, and therefore warrants further study.
Deciphering the Formulation Secret Underlying Chinese Huo-Clearing Herbal Drink
Authors: Wang Jianan , Zhou Bo , Hu Xiangdong , Dong Shuang , Hong Ming , Wang Jun , Chen Jian , Zhang Jiuliang , Zhang Qiyun , Li Xiaohua , Shikov Alexander N. , Hu Sheng , Hu Xuebo
Published: April 2021

Herbal teas or herbal drinks are traditional beverages that are prevalent in many cultures around the world. In Traditional Chinese Medicine, an herbal drink infused with different types of medicinal plants is believed to reduce the ‘Shang Huo’, or excessive body heat, a status of sub-optimal health. Although it is widely accepted and has a very large market, the underlying science for herbal drinks remains elusive. By studying a group of herbs for drinks, including ‘Gan’ (Glycyrrhiza uralensis Fisch. Ex DC.), ‘Ju’ (Dendranthema morifolium (Ramat.) Tzvelev), ‘Bu’ (Microcos paniculata L.), ‘Jin’ (Lonicera japonica Thunb.), ‘Xia’ (Prunella vulgaris L.), and ‘Ji’ (Plumeria rubra L.), the long-term jargon is connected with the inflammation of modern immunology through a few pro-inflammatory markers. In vitro studies have indicated that cellular inflammation is lowered by Ju and Jin either individually or synergistically with Gan. Among all herbs, only Gan detoxicated cellular toxicity of Bu in a dose dependent manner. The synergistic formulation of Ju and Gan, or Jin and Gan, in a reduction of Shang Huo, was tested in vivo. Both combinations exhibited a lower percentage of neutrophils, monocytes, and CD4+/CD8+ ratio in the blood, as well as inflammatory cytokines. Furthermore, body weight in the combinatory groups was more stable than treatments using single herbs. The combination of old traditional oriental methods with Western science logistics, has resulted in the formulation of different herbs into one concoction for the use of detoxification and synergism.
Vertically Integrated System with Microfabricated 3D Sensors and CO2 Microchannel Cooling
Authors: Da Via Cinzia , Petagna Paolo , Romagnoli Giulia , Hellenschmidt Desiree , Munoz-Sanchez Francisca , Dann Nicholas
Published: April 2021

The growing demand for miniaturized radiation-tolerant detection systems with fast responses and high-power budgets has increased the necessity for smart and efficient cooling solutions. Several groups have been successfully implementing silicon microfabrication to process superficial microchannels to circulate coolants, in particular, in high-energy physics experiments, where the combination of low material budget to reduce noise generated by multiple scattering events and high radiation fluences is required. In this study, we report tests performed on an 885-µm–thick vertically integrated system. The system consists of a layer of microfabricated silicon channels for temperature management integrated to radiation-tolerant microfabricated 3D sensors, with electrodes penetrating perpendicularly to the silicon bulk, bump-bonded to an ATLAS FE-I4 pixel readout chip of 100 µm thickness, 2 × 2 cm2, and 26,880 pixels (each measuring 250 × 50 μm2). The system’s electrical and temperature characterization under CO2 cooling as well as the response to minimum ionizing particles from radioactive sources and particle beams before and after 2.8 ×1015 neq cm−2 proton irradiation will be discussed.
When MINMOD Artifactually Interprets Strong Insulin Secretion as Weak Insulin Action
Authors: Ha Joon , Muniyappa Ranganath , Sherman Arthur S. , Quon Michael J.
Published: April 2021

We address a problem with the Bergman-Cobelli Minimal Model, which has been used for 40 years to estimate SI during an intravenous glucose tolerance test (IVGTT). During the IVGTT blood glucose and insulin concentrations are measured in response to an acute intravenous glucose load. Insulin secretion is often assessed by the area under the insulin curve during the first few minutes (Acute Insulin Response, AIR). The issue addressed here is that we have found in simulated IVGTTs, representing certain contexts, Minimal Model estimates of SI are inversely related to AIR, resulting in artifactually lower SI. This may apply to Minimal Model studies reporting lower SI in Blacks than in Whites, a putative explanation for increased risk of T2D in Blacks. The hyperinsulinemic euglycemic clamp (HIEC), the reference method for assessing insulin sensitivity, by contrast generally does not show differences in insulin sensitivity between these groups. The reason for this difficulty is that glucose rises rapidly at the start of the IVGTT and reaches levels independent of SI, whereas insulin during this time is determined by AIR. The minimal model in effect interprets this combination as low insulin sensitivity even when actual insulin sensitivity is unchanged. This happens in particular when high AIR results from increased number of readily releasable insulin granules, which may occur in Blacks. We conclude that caution should be taken when comparing estimates of SI between Blacks and Whites.
Loss of Cervical Sympathetic Chain Input to the Superior Cervical Ganglia Affects the Ventilatory Responses to Hypoxic Challenge in Freely-Moving C57BL6 Mice
Authors: Getsy Paulina M. , Coffee Gregory A. , Hsieh Yee-Hsee , Lewis Stephen J.
Published: April 2021

The cervical sympathetic chain (CSC) innervates post-ganglionic sympathetic neurons within the ipsilateral superior cervical ganglion (SCG) of all mammalian species studied to date. The post-ganglionic neurons within the SCG project to a wide variety of structures, including the brain (parenchyma and cerebral arteries), upper airway (e.g., nasopharynx and tongue) and submandibular glands. The SCG also sends post-ganglionic fibers to the carotid body (e.g., chemosensitive glomus cells and microcirculation), however, the function of these connections are not established in the mouse. In addition, nothing is known about the functional importance of the CSC-SCG complex (including input to the carotid body) in the mouse. The objective of this study was to determine the effects of bilateral transection of the CSC on the ventilatory responses [e.g., increases in frequency of breathing (Freq), tidal volume (TV) and minute ventilation (MV)] that occur during and following exposure to a hypoxic gas challenge (10% O2 and 90% N2) in freely-moving sham-operated (SHAM) adult male C57BL6 mice, and in mice in which both CSC were transected (CSCX). Resting ventilatory parameters (19 directly recorded or calculated parameters) were similar in the SHAM and CSCX mice. There were numerous important differences in the responses of CSCX and SHAM mice to the hypoxic challenge. For example, the increases in Freq (and associated decreases in inspiratory and expiratory times, end expiratory pause, and relaxation time), and the increases in MV, expiratory drive, and expiratory flow at 50% exhaled TV (EF50) occurred more quickly in the CSCX mice than in the SHAM mice, although the overall responses were similar in both groups. Moreover, the initial and total increases in peak inspiratory flow were higher in the CSCX mice. Additionally, the overall increases in TV during the latter half of the hypoxic challenge were greater in the CSCX mice. The ventilatory responses that occurred upon return to room-air were essentially similar in the SHAM and CSCX mice. Overall, this novel data suggest that the CSC may normally provide inhibitory input to peripheral (e.g., carotid bodies) and central (e.g., brainstem) structures that are involved in the ventilatory responses to hypoxic gas challenge in C57BL6 mice.
Lipid Droplets in Unicellular Photosynthetic Stramenopiles
Authors: Guéguen Nolwenn , Le Moigne Damien , Amato Alberto , Salvaing Juliette , Maréchal Eric
Published: April 2021

The Heterokonta or Stramenopile phylum comprises clades of unicellular photosynthetic species, which are promising for a broad range of biotechnological applications, based on their capacity to capture atmospheric CO2 via photosynthesis and produce biomolecules of interest. These molecules include triacylglycerol (TAG) loaded inside specific cytosolic bodies, called the lipid droplets (LDs). Understanding TAG production and LD biogenesis and function in photosynthetic stramenopiles is therefore essential, and is mostly based on the study of a few emerging models, such as the pennate diatom Phaeodactylum tricornutum and eustigmatophytes, such as Nannochloropsis and Microchloropsis species. The biogenesis of cytosolic LD usually occurs at the level of the endoplasmic reticulum. However, stramenopile cells contain a complex plastid deriving from a secondary endosymbiosis, limited by four membranes, the outermost one being connected to the endomembrane system. Recent cell imaging and proteomic studies suggest that at least some cytosolic LDs might be associated to the surface of the complex plastid, via still uncharacterized contact sites. The carbon length and number of double bonds of the acyl groups contained in the TAG molecules depend on their origin. De novo synthesis produces long-chain saturated or monounsaturated fatty acids (SFA, MUFA), whereas subsequent maturation processes lead to very long-chain polyunsaturated FA (VLC-PUFA). TAG composition in SFA, MUFA, and VLC-PUFA reflects therefore the metabolic context that gave rise to the formation of the LD, either via an early partitioning of carbon following FA de novo synthesis and/or a recycling of FA from membrane lipids, e.g., plastid galactolipids or endomembrane phosphor- or betaine lipids. In this review, we address the relationship between cytosolic LDs and the complex membrane compartmentalization within stramenopile cells, the metabolic routes leading to TAG accumulation, and the physiological conditions that trigger LD production, in response to various environmental factors.
Factors Associated With Post-traumatic Growth Among Healthcare Workers Who Experienced the Outbreak of MERS Virus in South Korea: A Mixed-Method Study
Authors: Hyun Hye Sun , Kim Mi Ja , Lee Jin Hyung
Published: April 2021

Background: Infectious disease outbreaks such as COVID-19 and MERS pose a major threat to healthcare workers' (HCWs) physical and mental health. Studies exploring the positive changes gained from adapting to traumatic events, known as post-traumatic growth (PTG), have attracted much attention. However, it is unclear which factors or experiences lead to PTG among HCWs. The purpose of this mixed-method study was to investigate factors associated with PTG among HCWs who experienced the MERS outbreak in South Korea, and fully describe their experience of developing PTG.

Methods: Quantitative data from 78 participants were collected using psychometric tools for Psychological distress, Resilience, and Support for coping, and Post-traumatic growth. Qualitative interviews were conducted with seven nurses. Data were analyzed using the qualitative content analysis method according to the sub-themes of resilience, which was the main factor associated with PTG.

Results: We found resilience to have a significant impact on PTG (ß =0.486, p = 0.001). Thus the qualitative interviews were analyzed using the core concepts of resilience. Qualitative interviews with nurses illustrated how participants experienced the development of resilience in terms of its sub-factors: hardiness, persistence, optimism, and support.

Conclusion: HCWs who endured the MERS outbreak showed high levels of PTG, and the analysis of the interview data provided a fuller understanding on the experience of remaining resilient and developing PTG. These results provide practical and pragmatic information helpful for developing intervention strategies and protocols that can help HCWs transform adversity into growth and development.
Game Transfer Phenomena and Problematic Interactive Media Use: Dispositional and Media Habit Factors
Authors: Ortiz de Gortari Angelica B. , Gackenbach Jayne
Published: April 2021

The study of the effects of interactive media has mainly focused on dysregulated behaviors, the conceptualization of which is supported by the paradigms of addiction. Research into Game Transfer Phenomena (GTP) examines the interplay between video game features, events while playing, and the manipulation of hardware, which can lead to sensory-perceptual and cognitive intrusions (e.g., hallucinations and recurrent thoughts) and self-agency transient changes (e.g., automatic behaviors) related to video games. GTP can influence the interpretation of stimuli and everyday interactions and, in contrast to gaming disorder, are relatively common and not necessarily negative. However, some players have reported feeling distress due to their GTP. This study focuses on how dispositional and interactive media habit factors are related to GTP and two forms of problematic interactive media [problematic video game playing (PVG) and problematic social media use (PSMU)]. A sample of 343 university students who played video games completed an online survey (58.7% male, 19–25 years old). Not all who had experienced GTP were identified as exhibiting PVG or PSMU, but all of those in the PVG group had experienced GTP. Overall, the profiles of the groups, including GTP (91.4%), PVG (28.5%), and PSMU (24.8%), were in accordance with previous findings. Those in the GTP and the PVG groups were characterized by being male, being highly engaged in the game (either while playing or via game-related activities), and showed preferences for game-related activities. However, while those in the GTP group were significantly more likely to be fantasy-prone, those with PVG were the ones who played most per day. Those in the PSMU group were characterized by being female and/or extroverted, frequently using social/sharing platforms, and seldom playing video games. A hierarchical binary logistic regression revealed that males were more likely to experience GTP. Increases in PVG, fantasy proneness, and neuroticism increased the odds of GTP. Future work can benefit from considering the role of GTP in gaming disorder, since intrusive thoughts, cognitive biases, and poor impulse control are pivotal in the initiation and maintenance of dysfunctional playing behaviors.
Media Exposure Related to the PTSS During COVID-19 Pandemic: The Mediating Role of Risk Perception
Authors: Wang Yiqing , Jiang Ling , Ma Shuang , Chen Qinian , Liu Chengbin , Ahmed Farooq , Shahid Muhammad , Wang Xiaohua , Guo Jing
Published: April 2021

Objectives:The objectives of this study are to assess the relationship between media exposure and post-traumatic stress symptoms (PTSS) and to highlight the underlying mechanisms mediated by risk perception.

Methods:This survey was conducted online in China from February 1st to February 10th, 2020. A total of 2,858 Chinese citizens aged ≥18 years from 31 provinces and autonomous regions were recruited to participate in a cross-sectional study. Self-report questionnaires were used to assess media exposure, PTSS, and risk perception.

Results:The prevalence of respondents with heightened PTSS scores was 22.2%. After controlling for covariates, media exposure (more than five times a day) was significantly and positively associated with a high level of PTSS (B= 4.11,p< 0.001), and risk perception (worry and severity) significantly mediated the relationship between media exposure and PTSS (all 95% CIs did not include 0).

Conclusions:Based on these findings, the frequency of media exposure was associated with PTSS. Risk perception (worry and severity) mediated the relationship between media exposure and PTSS. The mental health, particularly PTSS, of the general population should be closely monitored and “infodemics” should be combatted while addressing the COVID-19 outbreak; cognitive interventions may be promising.
ICD-11-Based Assessment of Social Media Use Disorder in Adolescents: Development and Validation of the Social Media Use Disorder Scale for Adolescents
Authors: Paschke Kerstin , Austermann Maria Isabella , Thomasius Rainer
Published: April 2021

Background: A problematic social media use (PSMU) in adolescents is a rising phenomenon often associated with higher perception of psychological stress and comorbid psychiatric disorders like depression. Since the ICD-11 introduced the very first internet-use related disorders, criteria for gaming (and online gambling) disorder can now be transferred to assess social media use disorder (SMUD). Therefore, the development and validation of a self-rating screening instrument for SMUD is of value to researchers and clinicians.

Method: The previously validated ICD-11-based Gaming Disorder Scale for Adolescents (GADIS-A) was adapted to measure SMUD (Social Media Use Disorder Scale for Adolescents, SOMEDIS-A). A representative sample of 931 adolescents aged 10 to 17 years and a respective parent participated in an online study. Item structure was evaluated by factorial analyses. Validated DSM-5-based instruments to assess PSMU by self- and parental ratings (SMDS, SMDS-P), adolescent depressive symptoms (PHQ-9), and stress perception (PSS-10) as well as single items on time spent with social media (SM, frequency and duration) were applied to assess criterion validity. Discrimination between pathological and non-pathological users was examined based on ROC analyses retrieved cut-off values and the results of a latent profile analysis.

Results: The new scale is best described by two factors reflecting cognitive-behavioral symptoms and associated negative consequences. The internal consistency was good to excellent. The SOMEDIS-A-sum score was positively correlated with PSMU, depression, and stress scores as well as the time spent with SM in a moderately to highly significant manner. Thus, good to excellent criterion validity is suggested.

Conclusions: SOMEDIS-A is the first successfully validated instrument to assess SMUD in adolescents based on the ICD-11 criteria of GD. Thus, it can support early detection in order to prevent symptom aggravation, chronification, and secondary comorbidities. It can contribute to the development of a standardized conceptualization and its two-factorial structure offers promising new insights into the evaluation of SM usage patterns. Further examination including clinical validation is desirable.
Propagation Model of Panic Buying Under the Sudden Epidemic
Authors: Fu Peihua , Jing Bailu , Chen Tinggui , Xu Chonghuan , Yang Jianjun , Cong Guodong
Published: April 2021

The sudden outbreak of COVID-19 at the end of 2019 has had a huge impact on people's lives all over the world, and the overwhelmingly negative information about the epidemic has made people panic for the future. This kind of panic spreads and develops through online social networks, and further spreads to the offline environment, which triggers panic buying behavior and has a serious impact on social stability. In order to quantitatively study this behavior, a two-layer propagation model of panic buying behavior under the sudden epidemic is constructed. The model first analyzes the formation process of individual panic from a micro perspective, and then combines the Susceptible-Infected-Recovered (SIR) Model to simulate the spread of group behavior. Then, through simulation experiments, the main factors affecting the spread of panic buying behavior are discussed. The experimental results show that: (1) the dissipating speed of individual panics is related to the number of interactions and there is a threshold. When the number of individuals involved in interacting is equal to this threshold, the panic of the group dissipates the fastest, while the dissipation speed is slower when it is far from the threshold; (2) The reasonable external information release time will affect the occurrence of the second panic buying, meaning providing information about the availability of supplies when an escalation of epidemic is announced will help prevent a second panic buying. In addition, when the first panic buying is about to end, if the scale of the second panic buying is to be suppressed, it is better to release positive information after the end of the first panic buying, rather than ahead of the end; and (3) Higher conformity among people escalates panic, resulting in panic buying. Finally, two cases are used to verify the effectiveness and feasibility of the proposed model.
Dung Beetles Help Keep Ecosystems Healthy
Authors: Manning Paul , Ong Xin Rui , Slade Eleanor M.
Published: April 2021

Dung beetles are a group of insects that primarily use the dung (poop) of mammals for feeding and nesting. These beetles are important for the breakdown and recycling of dung into the soil, enabling the nutrients in the dung to cycle through the ecosystem. Dung beetles provide many benefits for the health and functioning of both natural and human-modified ecosystems, such as dispersing seeds, reducing livestock parasites, and promoting plant growth. In this article, we will explore the basic life history of dung beetles. We then dig a little deeper into the importance of dung beetles within tropical forests and agricultural ecosystems.
A Multifluid Perspective on Multimessenger Modeling
Authors: Andersson Nils
Published: April 2021

This brief review introduces the notion of a relativistic multifluid system—a multi-component system with identifiable relative flows—and outlines a set of models for scenarios relevant for different astronomical observation channels. The specific problems used to illustrate the key principles include superfluid hydrodynamics (with relevance for radio and x-ray pulsar timing and gravitational-wave searches), heat flow (connecting to the problem of neutron star cooling and associated x-ray observations) and the coupling between matter and electromagnetism (linking to explosive phenomena like gamma-ray bursts and more subtle issues like the long-term evolution of a neutron star's magnetic field). We also comment on the coupling between matter and radiation, for which the multifluid approach would seem less appropriate. The main motivation of the survey is to illustrate less familiar aspects that come into play in multifluid problems, establish the relevant “language” and provide a platform for more detailed work on these issues.
Global Skewness and Coherence for Hypersonic Shock-Wave/Boundary-Layer Interactions with Pressure-Sensitive Paint
Authors: Running Carson L. , Juliano Thomas J.
Published: April 2021

The global surface pressure was measured on a 7° half-angle circular cone/flare model at a nominally zero angle of attack using pressure-sensitive paint (PSP). These experiments were conducted to illustrate fast PSP’s usefulness and effectiveness at measuring the unsteady structures inherent to hypersonic shock-wave/boundary-layer interactions (SWBLIs). Mean and fluctuating surface pressure was measured with a temperature-corrected, high-frequency-response (≈10 kHz) anodized-aluminum pressure-sensitive paint (AA-PSP) allowing for novel, global calculations of skewness and coherence. These analyses complement traditional SWBLI data-reduction methodologies by providing high-spatial-resolution measurements of the mean and fluctuating locations of the shock feet, as well as the frequency-dependent measure of the relationship between characteristic flow features. The skewness indicated the mean locations of the separation and reattachment shock feet as well as their fluctuations over the course of the test. The coherence indicated that the separation and reattachment shock feet fluctuate about their mean location at the same frequency as one another, but 180 degrees out of phase. This results in a large-scale ‘breathing motion’ of the separated region characteristic of large separation bubbles. These experimental findings validate the usefulness of AA-PSP, and associated data-reduction methodologies, to provide global physical insights of unsteady SWBLI surface behavior in the hypersonic flow regime. Similar methodologies can be incorporated in future experiments to investigate complex and novel SWBLIs.
Analysis of Re-Heterosis for Yield and Fruit Quality in Restructured Hybrids, Generated from Crossings among Tomato Recombinant Lines
Authors: Avdikos Ilias D. , Nteve Georgia-Maria , Apostolopoulou Athanasia , Tagiakas Rafail , Mylonas Ioannis , Xynias Ioannis N. , Papathanasiou Fokion , Kalaitzis Panagiotis , Mavromatis Athanasios G.
Published: April 2021

Randomized complete block design was used, with three replications. Heterosis for yield and fruit quality characteristics was studied, and expressed as Relative heterosis, heterobeltiosis and Standard heterosis. It would be expected, according to the dominance model, that the heterosis recorded after crossing the recombinant lines, having only a small portion of recessive deleterious alleles, would be minimal. The results showed that the elite recombinant inbred lines became the parents of elite restructured hybrids, with increased levels of re-heterosis for all characters measured. This may prove that dominance is not the only case in explaining heterosis in tomato for yield components and fruit quality characteristics. Several recombinant lines, and most of the new reconstructed F1 hybrids, showed excellent productivity under a low input farming system. The evaluation and selection of the different types of cultivars (recombinant pure lines or reconstructed hybrids) under low input conditions could point towards the most suitable/ideal genotype for organic cultivation.
Antimicrobial Resistance Patterns and Dynamics of Extended-Spectrum β-Lactamase-Producing Uropathogenic Escherichia coli in Cusco, Peru
Authors: Loyola Steev , Concha-Velasco Fátima , Pino-Dueñas Jimena , Vasquez-Luna Nancy , Juarez Paola , Llanos Carlos , Salvatierra Guillermo , Tamariz Jesus , Lescano Andres G.
Published: April 2021

Urinary tract infections (UTIs) are a common human infection. Antibiotic resistance in extended-spectrum β-lactamase (ESBL)-producing uropathogenic E. coli (UPEC) is a major therapeutic challenge due to limited treatment alternatives. The aim was to characterize the antimicrobial resistance (AMR) and dynamics of ESBL-producing UPEC isolates from UTI cases seen at a local hospital in Cusco, Peru. Ninety-nine isolates from respective patients were characterized against 18 different antibiotics. Latent class analysis (LCA) was used to evaluate the dynamics across the study time according to resistance patterns. The median age of patients was 51 years old, and nearly half were women. ESBL-producing UPEC isolates were slightly more frequent in outpatient services than emergency rooms, and there were higher resistance rates in males compared to females. Half of the ESBL producers were resistant to aminoglycosides and nitrofurantoin. Cefoxitin and fosfomycin resistance was 29.3% and 14.1%, respectively. Resistance to carbapenems was not observed. All isolates were multidrug-resistant bacteria, and 16.2% (16/99) were also classified as extensively drug-resistant bacteria. The resistance patterns varied across the study time and differed regarding sex and healthcare service. The study revealed high levels of AMR to commonly used antimicrobials and a dynamic circulation of ESBL-producing UPEC isolates with varying resistance patterns.