bluuebunny/crossref_metadata_2025 huggingface dataset:
Compressive Properties and Hydraulic Permeability of Human Meniscus: Relationships With Tissue Structure and Composition
Authors: Morejon Andy , Norberg Christopher D. , De Rosa Massimiliano , Best Thomas M. , Jackson Alicia R. , Travascio Francesco
Published: February 2021

The meniscus is crucial in maintaining knee function and protecting the joint from secondary pathologies, including osteoarthritis. The meniscus has been shown to absorb up to 75% of the total load on the knee joint. Mechanical behavior of meniscal tissue in compression can be predicted by quantifying the mechanical parameters including; aggregate modulus (H) and Poisson modulus (ν), and the fluid transport parameter: hydraulic permeability (K). These parameters are crucial to develop a computational model of the tissue and for the design and development of tissue engineered scaffolds mimicking the native tissue. Hence, the objective of this study was to characterize the mechanical and fluid transport properties of human meniscus and relate them to the tissue composition. Specimens were prepared from the axial and the circumferential anatomical planes of the tissue. Stress relaxation tests yielded the H, while finite element modeling was used to curve fit for ν and K. Correlations of moduli with water and glycosaminoglycans (GAGs) content were investigated. On average H was found to be 0.11 ± 0.078 MPa, ν was 0.32 ± 0.057, and K was 2.9 ± 2.27 × 10−15 m4N−1s−1. The parameters H, ν, and K were not found to be statistically different across compression orientation or compression level. Water content of the tissue was 77 ± 3.3% while GAG content was 8.79 ± 1.1%. Interestingly, a weak negative correlation was found between H and water content (R2 ~ 34%) and a positive correlation between K and GAG content (R2 ~ 53%). In conclusion, while no significant differences in transport and compressive properties can be found across sample orientation and compression levels, data trends suggest potential relationships between magnitudes of H and K, and GAG content.
Guanidino-Acetic Acid: A Scarce Substance in Biomass That Can Regulate Postmortem Meat Glycolysis of Broilers Subjected to Pre-slaughter Transportation
Authors: Zhang Bolin , Liu Ning , He Zhen , Song Peiyong , Hao Meilin , Xie Yuxiao , Li Jiahui , Liu Rujie , Sun Zewei
Published: February 2021

The different substances in biomass can regulate the metabolism and reproduction of broilers. Guanidino-acetic acid (GAA) is a natural feed additive that showed a potential application in dietary for broilers, while its amount is scarce in biomass. The objective of the present study was to investigate the effects of dietary supplemented with GAA on muscle glycolysis of broilers subjected to pre-slaughter transportation. A total of 160 Qiandongnan Xiaoxiang chickens were randomly assigned into three treatments, including a basal control diet without GAA supplementation (80 birds) or supplemented with 600 mg/kg (40 birds) or 1,200 mg/kg (40 birds) GAA for 14 days. At the end of the experiment, the control group was equally divided into two groups, thus resulting in four groups. All birds in the four groups aforementioned were separately treated according to the following protocols: (1) no transport of birds of the control group fed with the basal diet; (2) a 3-h transport of birds of the control group fed with the basal diet; (3) a 3-h transport of birds fed with diets supplemented with 600 mg/kg GAA; and (4) a 3-h transport of birds fed with diets supplemented with 1,200 mg/kg GAA. The results demonstrated that 3-h pre-slaughter transport stress increased corticosterone contents and lowered glucose contents in plasma (P < 0.05), decreased pH24h (P < 0.05), and resulted in inferior meat quality evidenced by elevating the drip loss, cooking loss, and L∗ value (P < 0.05). Meanwhile, 3-h pre-slaughter transport stress decreased the contents of Cr and ATP in muscle (P < 0.05) and elevated the ratio of AMP:ATP and the glycolytic potential of muscle (P < 0.05). Moreover, 3-h pre-slaughter transport resulted in a significant elevation of mRNA expressions of LKB1 and AMPKα2 (P < 0.05), as well as the increase in protein abundances of LKB1 phosphorylation and AMPKα phosphorylation (P < 0.05). However, 1,200 mg/kg GAA supplementation alleviated negative parameters in plasma, improved meat quality, and ameliorated postmortem glycolysis and energy metabolism through regulating the creatine–phosphocreatine cycle and key factors of AMPK signaling. In conclusion, dietary supplementation with 1,200 mg/kg GAA contributed to improving meat quality via ameliorating muscle energy expenditure and delaying anaerobic glycolysis of broilers subjected to the 3-h pre-slaughter transport.
Recovery of Polyhydroxyalkanoates From Single and Mixed Microbial Cultures: A Review
Authors: Pagliano Giorgia , Galletti Paola , Samorì Chiara , Zaghini Agnese , Torri Cristian
Published: February 2021

An overview of the main polyhydroxyalkanoates (PHA) recovery methods is here reported, by considering the kind of PHA-producing bacteria (single bacterial strains or mixed microbial cultures) and the chemico-physical characteristics of the extracted polymer (molecular weight and polydispersity index). Several recovery approaches are presented and categorized in two main strategies: PHA recovery with solvents (halogenated solvents, alkanes, alcohols, esters, carbonates and ketones) and PHA recovery by cellular lysis (with oxidants, acid and alkaline compounds, surfactants and enzymes). Comparative evaluations based on the recovery, purity and molecular weight of the recovered polymers as well as on the potential sustainability of the different approaches are here presented.
Polarimetric Measurements of Surface Chirality Based on Linear and Nonlinear Light Scattering
Authors: Gogoi Ankur , Konwer Surajit , Zhuo Guan-Yu
Published: February 2021

A molecule, molecular aggregate, or protein that cannot be superimposed on its mirror image presents chirality. Most living systems are organized by chiral building blocks, such as amino acids, peptides, and carbohydrates, and any change in their molecular structure (i.e., handedness or helicity) alters the biochemical and pharmacological functions of the molecules, many of which take place at surfaces. Therefore, studying surface chirogenesis at the nanoscale is fundamentally important and derives various applications. For example, since proteins contain highly ordered secondary structures, the intrinsic chirality can be served as a signature to measure the dynamics of protein adsorption and protein conformational changes at biological surfaces. Furthermore, a better understanding of chiral recognition and separation at bio-nanointerfaces is helpful to standardize chiral drugs and monitor the synthesis of adsorbents with high precision. Thus, exploring the changes in surface chirality with polarized excitations would provide structural and biochemical information of the adsorbed molecules, which has led to the development of label-free and noninvasive measurement tools based on linear and nonlinear optical effects. In this review, the principles and selected applications of linear and nonlinear optical methods for quantifying surface chirality are introduced and compared, aiming to conceptualize new ideas to address critical issues in surface biochemistry.
Functionalized CNTs with DOPO and Silicon Containing Agents: Effective Reinforcer for Thermal and Flame Retardant Properties of Polystyrene Nanocomposites
Authors: Shi Congling , Qian Xiaodong , Jing Jingyun , Che Honglei
Published: February 2021

DOPO and silicon containing agents modified multiwalled carbon nanotubes (MCNTs) were synthesized through sol-gel process and MCNTs are introduced into polystyrene (PS) through in situ polymerization. TEM observations and FTIR results of MCNTs demonstrated that the MCNT nanofillers were coated with the organic/inorganic flame retardant compound. Moreover, the TEM results of the composites indicate that MCNTs dispersed in polystyrene PS matrix uniformly due to the modification. The PS/MCNTs composites showed improved thermal stability as well as flame retardant properties in comparison with PS/CNTs composites, which are due to the good dispersion of MCNT in the PS matrix. MCNTs in the PS matrix can also reduce the peak heat release rate, total heat release and improve the smoke suppression performance. The improved flame retardant properties are attributed to the char reinforcing effect of CNTs, which can provide enough time for MCNTs and organic/inorganic compound to trap the degradation of polymer chains and catalyze the formation of char. The char layers can not only serve as an efficient insulating barrier to reduce the exposure of PS matrix to heat source but also retard the releasing of combustible gas.
Mechanisms and Perspectives of Sodium-Glucose Co-transporter 2 Inhibitors in Heart Failure
Authors: Zeng Qingchun , Zhou Qing , Liu Weitao , Wang Yutong , Xu Xingbo , Xu Dingli
Published: February 2021

Heart failure (HF) is a common complication or late-stage manifestation of various heart diseases. Numerous risk factors and underlying causes may contribute to the occurrence and progression of HF. The pathophysiological mechanisms of HF are very complicated. Despite accumulating advances in treatment for HF during recent decades, it remains an intractable clinical syndrome with poor outcomes, significantly reducing the quality of life and expectancy of patients, and imposing a heavy economic burden on society and families. Although initially classified as antidiabetic agents, sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated reduced the prevalence of hospitalization for HF, cardiovascular death, and all-cause death in several large-scale randomized controlled clinical trials. These beneficial effects of SGLT-2 inhibitors can be attributed to multiple hemodynamic, inflammatory and metabolic mechanisms, not only reducing the serum glucose level. SGLT2 inhibitors have been used increasingly in treatment for patients with HF with reduced ejection fraction due to their surprising performance in improving the prognosis. In addition, their roles and mechanisms in patients with HF with preserved ejection fraction or acute HF have also attracted attention. In this review article, we discuss the possible mechanisms and applications of SGLT2 inhibitors in HF.
Impact of European Beech Forest Diversification on Soil Organic Carbon and Total Nitrogen Stocks–A Meta-Analysis
Authors: Rehschuh Stephanie , Jonard Mathieu , Wiesmeier Martin , Rennenberg Heinz , Dannenmann Michael
Published: February 2021

Drought-sensitive European beech forests are increasingly challenged by climate change. Admixing other, preferably more deep-rooting, tree species has been proposed to increase the resilience of beech forests to drought. This diversification of beech forests might also affect soil organic carbon (SOC) and total nitrogen (TN) stocks that are relevant for a wide range of soil functions and ecosystem services, such as water and nutrient retention, filter functions and erosion control. Since information of these effects is scattered, our aim was to synthesize results from studies that compared SOC/TN stocks of beech monocultures with those of beech stands mixed with other tree species as well as monocultures of other tree species. We conducted a meta-analysis including 38 studies with 203, 220, and 160 observations for forest floor (i.e., the organic surface layer), mineral soil (0.5 m depth) and the total soil profile, respectively. Monoculture conifer stands had higher SOC stocks compared to monoculture beech in general, especially in the forest floor (up to 200% in larch forests). In contrast, other broadleaved tree species (oak, ash, lime, maple, hornbeam) showed lower SOC stocks in the forest floor compared to beech, with little impact on total SOC stocks. Comparing mixed beech-conifer stands (average mixing ratio with regard to number of trees 50:50) with beech monocultures revealed significantly higher total SOC stocks of around 9% and a smaller increase in TN stocks of around 4%. This equaled a SOC accrual of 0.1 Mg ha−1 yr−1. In contrast, mixed beech-broadleaved stands did not show significant differences in total SOC stocks. Conifer admixture effects on beech forest SOC were of additive nature. Admixing other tree species to beech monoculture stands was most effective to increase SOC stocks on low carbon soils with a sandy texture and nitrogen limitation (i.e., a high C/N ratio and low nitrogen deposition). We conclude that, with targeted admixture measures of coniferous species, an increase in SOC stocks in beech forests can be achieved as part of the necessary adaptation of beech forests to climate change.
Identification of a 14-Gene Prognostic Signature for Diffuse Large B Cell Lymphoma (DLBCL)
Authors: Feng Pengcheng , Li Hongxia , Pei Jinhong , Huang Yan , Li Guixia
Published: February 2021

Although immunotherapy is a potential strategy to resist cancers, due to the inadequate acknowledge, this treatment is not always effective for diffuse large B cell lymphoma (DLBCL) patients. Based on the current situation, it is critical to systematically investigate the immune pattern. According to the result of univariate and multivariate cox proportional hazards, LASSO regression and Kaplan-Meier survival analysis on immune-related genes (IRGs), a prognostic signature, containing 14 IRGs (AQP9, LMBR1L, FGF20, TANK, CRP, ORM1, JAK1, BACH2, MTCP1, IFITM1, TNFSF10, FGF12, RFX5, and LAP3), was built. This model was validated by external data, and performed well. DLBCL patients were divided into low- and high-risk groups, according to risk scores from risk formula. The results of CIBERSORT showed that different immune status and infiltration pattern were observed in these two groups. Gene set enrichment analysis (GSEA) indicated 12 signaling pathways were significantly enriched in the high-risk group, such as natural killer cell-mediated cytotoxicity, toll-like receptor signaling pathway, and so on. In summary, 14 clinically significant IRGs were screened to build a risk score formula. This formula was an accurate tool to provide a certain basis for the treatment of DLBCL patients.
Simvastatin in the Prevention of Recurrent Pancreatitis: Design and Rationale of a Multicenter Triple-Blind Randomized Controlled Trial, the SIMBA Trial
Authors: Cárdenas-Jaén Karina , Vaillo-Rocamora Alicia , Gracia Ángel , Garg Pramoud K. , Zapater Pedro , Papachristou Georgios I. , Singh Vikesh K. , Wu Bechien U. , de-Madaria Enrique
Published: February 2021

Background: One in every four patients with a first episode of non-gallstone-related acute pancreatitis (AP) develops recurrent disease. Recurrent episodes of AP or acute flares of chronic pancreatitis (CP) are associated with decreased quality of life and progression of the disease. Besides removing the etiology of pancreatitis (which sometimes is not possible), there are no effective measures to prevent recurrence. Meta-analyses of randomized controlled trials, as well as epidemiological and cohort studies, suggest that statins may be protective against the development of index AP.

Methods: The SIMBA study is a triple-blind randomized placebo-controlled, parallel-group multicenter trial. Patients with recurrent AP or with acute flares of CP (at least two episodes in the last 12 months) will be randomized to receive simvastatin 40 mg daily or placebo. During a 3-year study period, 144 patients (72 per arm of treatment) from 26 centers will be enrolled. The patients will receive the study treatment for 1 year. The primary aim is to compare the recurrence of AP or acute flares in CP. Secondary endpoints include the incidence of new-onset diabetes mellitus, new-onset exocrine pancreatic insufficiency (EPI), new-onset imaging signs of CP, frequency of all-cause hospital admissions, severity of AP, adherence to treatment, and frequency of adverse events.

Discussion: The SIMBA trial will ascertain whether simvastatin, a safe, widely used and inexpensive drug, can change the natural course of recurrent pancreatitis.

Trial Registration: ClinicalTrials.gov Identifier: NCT04021498
Efficacy of Systemic Treatments of Nail Psoriasis: A Systemic Literature Review and Meta-Analysis
Authors: Zhang Xuan , Xie Bingbing , He Yanling
Published: February 2021

Importance: Nail involvement is a common condition in patients with psoriasis. The treatment of nail psoriasis is considered challenging and is often left untreated by physicians.

Objective: To assess the efficacy of current systemic treatments on nail psoriasis.

Data Sources: PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for relevant articles from inception to September 1, 2020. Included articles were restricted to English language and human studies.

Study Selection: This was a systematic literature review with meta-analysis. Thirty-five random control trials that evaluated systemic therapies for nail psoriasis were selected in the systemic review. Among them, we retained 14 trials for meta-analysis.

Data Extraction and Synthesis: This study was conducted in accordance with the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. All steps were performed by two independent investigators, and any disagreements were resolved by a third investigator. Meta-analysis of aggregated study data was conducted to assess therapeutic efficacy. The use of random-effects model was based on high heterogeneity as a variable endpoint in different studies.

Main Outcomes and Measures: Therapeutic effects on nail psoriasis were expressed in terms of effect sizes with 95% CIs.

Results: We included 35 random control trials (RCTs) in this systemic review. At baseline, a high prevalence (62.1%) of nail psoriasis was confirmed. The meta-analysis included 14 trials highlighting that biologic and small-molecule therapies were effective in treating nail psoriasis with variable effect size magnitudes [−0.89 (−1.10, −0.68), I2 = 84%]. In particular, tofacitinib and ixekizumab showed the most significant scale of effect size magnitudes in treating nail psoriasis (−1.08 points and −0.93 points, respectively). We also found that a higher dose of tofacitinib and ixekizumab had similar effectiveness, and anti-IL-17 agents seem to be superior in effectiveness compared to anti-TNF-α therapies in the treatment of nail psoriasis. However, these results must be displayed carefully as variable endpoints in different studies.

Conclusions and Relevance: This study provides a comprehensive overview of systemic treatments for nail psoriasis. For patients with psoriatic nail damage who are candidates of systemic therapies, the priority should be given to administering biologic and small-molecule therapies, especially anti-IL-17 drugs.
D1R- and D2R-Medium-Sized Spiny Neurons Diversity: Insights Into Striatal Vulnerability to Huntington’s Disease Mutation
Authors: Bergonzoni Guendalina , Döring Jessica , Biagioli Marta
Published: February 2021

Huntington’s disease (HD) is a devastating neurodegenerative disorder caused by an aberrant expansion of the CAG tract within the exon 1 of the HD gene, HTT. HD progressively impairs motor and cognitive capabilities, leading to a total loss of autonomy and ultimate death. Currently, no cure or effective treatment is available to halt the disease. Although the HTT gene is ubiquitously expressed, the striatum appears to be the most susceptible district to the HD mutation with Medium-sized Spiny Neurons (MSNs) (D1R and D2R) representing 95% of the striatal neuronal population. Why are striatal MSNs so vulnerable to the HD mutation? Particularly, why do D1R- and D2R-MSNs display different susceptibility to HD? Here, we highlight significant differences between D1R- and D2R-MSNs subpopulations, such as morphology, electrophysiology, transcriptomic, functionality, and localization in the striatum. We discuss possible reasons for their selective degeneration in the context of HD. Our review suggests that a better understanding of cell type-specific gene expression dysregulation within the striatum might reveal new paths to therapeutic intervention or prevention to ameliorate HD patients’ life expectancy.
Effects of Selective Serotonin Reuptake Inhibitors on Depression-Like Behavior in a Laser-Induced Shock Wave Model
Authors: Seno Soichiro , Tomura Satoshi , Miyazaki Hiromi , Sato Shunichi , Saitoh Daizoh
Published: February 2021

Primary blast injury can result in depression-like behavior in the long-term. However, the effects of the selective serotonin reuptake inhibitor (SSRI) on the depression induced by mild blast traumatic brain injury (bTBI) in the long-term remain unclear. We generated a mouse model of mild bTBI using laser-induced shock wave (LISW) and administered an SSRI to mice by oral gavage for 14 days after LISW exposure. This study aimed to investigate the mechanisms of SSRI-mediated alleviation of depression-like behavior induced by mild bTBI. Animals were divided into three groups: sham, LISW-Vehicle, and LISW-SSRI. LISW was applied to the head of anesthetized mice at 0.5 J/cm2. Twenty-eight days after the LISW, mice in the LISW-SSRI group exhibited reduced depression-like behavior, a significant increase in the number of cells co-stained for 5-bromo-2'-deoxyuridine (Brd-U) and doublecortin (DCX) in the dentate gyrus (DG) as well as increased brain-derived neurotrophic factor (BDNF) and serotonin levels in the hippocampus compared to the sham and LISW-Vehicle groups. Additionally, levels of phosphorylated cAMP response element binding protein (pCREB) in the DG were significantly decreased in the LISW-Vehicle group compared to that in the sham group. Importantly, pCREB levels were not significantly different between LISW-SSRI and sham groups suggesting that SSRI treatment may limit the downregulation of pCREB induced by mild bTBI. In conclusion, recovery from depression-like behavior after mild bTBI may be mediated by hippocampal neurogenesis induced by increased BDNF and serotonin levels as well as the inhibition of pCREB downregulation in the hippocampus.
The Associations Between Sleep Architecture and Metabolic Parameters in Patients With Obstructive Sleep Apnea: A Hospital-Based Cohort Study
Authors: Feng Nana , Yang Jundong , Xu Huajun , Zhang Chujun , Wang Fan , Wu Xiaolin , Gu Meizhen
Published: February 2021

Background and Objectives: The associations between objective sleep architecture and metabolic parameters have been rarely studied in patients with obstructive sleep apnea (OSA). Here, we evaluated the associations between objective sleep measures derived via polysomnography (PSG) and metabolic parameters.

Methods: A total of 2,308 subjects with suspected OSA were included. We measured common metabolic parameters such as body mass index (BMI) and glucose, insulin, blood pressure, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels. All subjects underwent full-night PSG. PSG sleep parameters included total sleep time (TST), time spent in slow-wave sleep (SWS) and rapid eye movement (REM) sleep, sleep efficiency, and the microarousal index (MAI).

Results: The TST correlated with the BMI, glucose level, and systolic blood pressure. The SWS/TST ratio correlated with BMI and glucose, TC, and TG levels. The REM/TST ratio correlated with BMI, glucose, insulin, and TG levels, and diastolic blood pressure. We found significant relationships between sleep efficiency and BMI, glucose levels, and TG levels. The MAI was significantly correlated with all metabolic parameters. After adjustment for age, gender, smoking status, alcohol use, apnea hypopnea index, and oxygen desaturation index (ODI), multiple linear regression analysis showed that the MAI was independently associated with glucose level, TC, HDL, and LDL. REM/TST ratio was positively associated with diastolic blood pressure but negatively associated with glucose metabolism.

Conclusions: Though some independent correlation between sleep and metabolic parameters was confirmed, only weak associations were observed, suggesting a clinically negligible influence of sleep structure. Further prospective studies are warranted to confirm our findings.
Case Report: Chorea-Acanthocytosis Presents as Epilepsy in a Consanguineous Family With a Nonsense Mutation of in VPS13A
Authors: Luo Fang-Mei , Deng Ming-Xing , Yu Rong , Liu Lv , Fan Liang-Liang
Published: February 2021

Chorea-Acanthocytosis (ChAc), a rare autosomal recessive inherited neurological disorder, originated from variants in Vacuolar Protein Sorting 13 homolog A (VPS13A) gene. The main symptoms of ChAc contain hyperkinetic movements, seizures, cognitive impairment, neuropsychiatric symptoms, elevated serum biochemical indicators, and acanthocytes detection in peripheral blood smear. Recently, researchers found that epilepsy may be a presenting and prominent symptom of ChAc. Here, we enrolled a consanguineous family with epilepsy and non-coordinated movement. Whole exome sequencing was employed to explore the genetic lesion of the family. After data filtering, co-separation analysis was performed by Sanger sequencing and bioinformatics analysis, the homozygous nonsense variant (NM_033305.2: c.8282C>G, p.S2761X) of VPS13A were identified which could be genetic factor of the patient. No other meaningful mutations were detected. This mutation (p.S2761X) led to a truncated protein in exon 60 of the VPS13A gene, was simultaneously absent in our 200 local control participants. The homozygous mutation (NM_033305.2: c.8282C>G, p.S2761X) of VPS13A may be the first time be identified in ChAc patient with epilepsy. Our study assisted to the diagnosis of ChAc in this patient and contributed to the genetic diagnosis and counseling of families with ChAc presented as epilepsy. Moreover, we further indicated that epilepsy was a crucial phenotype in ChAc patients caused by VPS13A mutations.
Re-Clustering and Profiling of Digestive System Tumors According to Microenvironment Components
Authors: Wang Yongwei , Guo Sen , Chen Zhihong , Bai Bing , Wang Shuo , Gao Yaxian
Published: February 2021

Background

Immunotherapy has become the most promising therapy in digestive system tumors besides conventional chemotherapy and radiotherapy. But only a few patients can benefit from different types of immunotherapies, such as immune checkpoint blockade (ICB). To identify these ICB-susceptible patients, methods are urgently needed to screen and profile subgroups of patients with different responsiveness to ICB.

Methods

This study carried out analysis on patients with digestive system tumors that were obtained from Cancer Genome Atlas (TCGA) cohorts. The analyses were mainly performed using GraphPad Prism 7 and R language.

Results

We have quantified the microenvironmental components of eight digestive system tumor patients in TCGA cohorts and evaluated their clinical value. We re-clustered patients based on their microenvironment composition and divided these patients into six clusters. The differences between these six clusters were profiled, including survival conditions, enriched biological processes, genomic mutations, and microenvironment traits. Cluster 3 was the most immune-related cluster, exhibiting a high infiltration of non-tumor components and poor survival status, along with an inhibitory immune status, and we found that patients with high stromal score indicated a poor response in ICB cohort.

Conclusions

Our research provides a new strategy based on the microenvironment components for the reclassification of digestive system tumors, which could provide guidance for prognosis judgment and treatment response prediction like ICB.
Dissecting Outcomes: Should Cytoreductive Nephrectomy Be Performed for Patients With Metastatic Renal Cell Carcinoma With Sarcomatoid Dedifferentiation?
Authors: Adashek Jacob J. , Zhang Yumeng , Skelton William Paul , Bilotta Alyssa , Chahoud Jad , Zemp Logan , Li Jiannong , Dhillon Jasreman , Manley Brandon , Spiess Philippe E.
Published: February 2021

Background

It is highly contested whether cytoreductive nephrectomy for treating advanced renal cell carcinoma (RCC) with sarcomatoid features (sRCC) benefits overall survival. Patients with sRCC are known to have a poor prognosis, and these tumors have a more aggressive biology than those without sarcomatoid features.

Methods

Patients with clear cell RCC or non–clear cell RCC underwent cytoreductive nephrectomy in efforts to improve overall survival (OS). Patients were stratified by presence or absence of histologic sarcomatoid features within tumor samples.

Results

Of 167 patients who underwent cytoreductive nephrectomy, 127 had clear cell RCC, of whom 14 had sarcomatoid features, and 40 had non–clear cell RCC, of whom 13 had sarcomatoid features. Median age of the cohort was 62 years (range, 56.5–69 years). The cohort included 119 male (71.3%) and 48 (28.7%) female patients. Among all patients with advanced RCC, having sRCC had a significantly worse OS after cytoreductive nephrectomy (30 vs 8 months; hazard ratio [HR], 2.88; P <0.0001). Additionally, favorable-risk patients had significantly longer OS compared to intermediate- or poor-risk patients (56 vs 30 vs 10 months; HR, 0.21; P =0.00016). For patients with clear cell RCC, having sRCC conferred a significantly poorer survival (30 vs 9 months; HR, 2.82; P=0.0035). Patients with non–clear cell sRCC also had significantly worse outcomes compared to patients whose tumors did not have sarcomatoid features (30 vs 6.5 months; HR, 3; P =0.009). When patients with sRCC were stratified by whether there was >10% or ≤10% sarcomatoid features present within the sample, there was no significant difference in OS (8 vs 8.5 months; P =0.32).

Conclusions

Sarcomatoid features within tumor histology confer significantly poor prognosis. Patients with sRCC, regardless of clear cell vs non–clear cell histology, have significantly shorter OS. Even among patients with 10% or less sarcomatoid features, there was no OS benefit to cytoreductive nephrectomy. Based on our findings, there appears to be a limited to no role of cytoreductive nephrectomy if sRCC is identified on pretreatment biopsy. The role of radiomics and pre-operative biopsies may confer significant benefit in this patient population.
Case Report: Systemic Small-Vessel Vasculitis in an Adolescent With Active Ulcerative Colitis
Authors: Bouhuys Marleen , Armbrust Wineke , van Rheenen Patrick F.
Published: February 2021

Introduction: Small-vessel vasculitis (SVV) is a rare immunological disease that affects arterioles, capillaries and venules. It causes purpura, but can also manifest in other organs, including the gastrointestinal tract. SVV and inflammatory bowel disease (IBD) co-occur more frequently than would be expected by chance.

Case description: A 16-year-old girl, who had been diagnosed with ulcerative colitis (UC) 2 years earlier at a general hospital, developed purpura, progressive abdominal pain with frequent bloody diarrhea and frontotemporal headache and swelling while on azathioprine and mesalamine maintenance therapy. Serology was positive for perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) without antiprotease- or myeloperoixidase antibodies. Endoscopy revealed active left-sided UC and atypical ulcerations in the ascending colon. Biopsies of these ulcerations and of affected skin revealed leukocytoclastic vasculitis. Initially this was interpreted as an extraintestinal manifestation of UC that would subside when remission was induced, consequently infliximab was started. Over the next 3 weeks she developed severe burning pain in her right lower leg that progressed to a foot drop with numbness and the purpura progressed to bullous lesions. The diagnosis was adjusted to ANCA-associated vasculitis with involvement of skin, bowel and peripheral nerves. Infliximab was discontinued and induction treatment with high-dose prednisolone and cyclophosphamide was given until remission of SVV and UC was achieved. Subsequently, infliximab induction and maintenance was re-introduced in combination with methotrexate. Remission has been maintained successfully for over 2 years now. The foot drop only partly resolved and necessitated the use of an orthosis.

Conclusion: Pediatric patients with IBD who present with purpuric skin lesions and abdominal pain should be evaluated for systemic involvement of SVV, which includes endoscopic evaluation of the gastrointestinal tract. We discuss a practical approach to the diagnosis, evaluation and management of systemic SVV with a focus on prompt recognition and early aggressive therapy to improve outcome.
Clinical Efficacy and Safety of Propranolol in the Prevention and Treatment of Retinopathy of Prematurity: A Meta-Analysis of Randomized Controlled Trials
Authors: Kong Haibo B. , Zheng Guoyuan Y. , He Baomei M. , Zhang Ying , Zhou Qin
Published: February 2021

Objective: To perform a meta-analysis of randomized controlled trials verifying clinical efficacy and safety of propranolol in pre-term newborns with retinopathy of prematurity (ROP).

Methods: We searched the literature databases (Pubmed, Embase, The Cochrane Library, Web of Science, CNKI, WanFang, VIP, CBM) for publications before August 10, 2020, and the World Health Organization's International Clinical Trials Registry and ClinicalTrials.gov for ongoing trials. Randomized controlled trials (RCTs) of propranolol for the prevention or treatment of ROP were included. The quality of the included studies was primarily assessed by the RCT tool of the Cochrane Collaboration. The included studies were quantified using a meta-analysis of relative risk (RR) estimated with a random effect model.

Results: Our original search identified 171 articles, and five studies met our criteria. A meta-analysis was performed that showed that infants orally treated with propranolol had a decreased risk of disease progression: stage progression had an RR = 0.65 [95% confidence interval (CI), 0.47–0.88]), plus disease had an RR = 0.43 [95% CI, 0.22–0.82]. The demands for additional treatments had similar protective results: laser photocoagulations had an RR = 0.55 [95% CI, 0.35–0.86]), and intravitreal injection of anti-vascular endothelial growth factor had an RR = 0.45 [95% CI, 0.22–0.90]). The oral administration of propranolol was associated with an increased risk of adverse events (RR = 2.01 [95% CI, 1.02–3.97]). High-risk adverse events included bradycardia, hypotension, not gaining enough weight, bronchospasm, hypoglycemia, apnea, and increasing ventilator need. Subgroup analysis of ROP phases and stages found that the risk in stage 2 ROP of the second phase and the individual risk factors (stage progression, RR = 0.42 [95% CI, 0.27–0.65]; plus disease, RR = 0.40 [95% CI, 0.17–0.93]; laser photocoagulation, RR = 0.31 [95% CI, 0.14–0.68]) have statistically significant differences compared with other phases and stages.

Conclusions: Pre-term newborns with ROP, especially in stage 2 ROP of the second phase, who were orally given propranolol have a reduced risk of disease progression and demand for additional treatments, but the safety needs more attention.
Toward Waveguide-Based Optical Chromatography
Authors: Neves Antonio A. R. , Moreira Wendel L. , Fontes Adriana , Euser Tijmen G. , Cesar Carlos L.
Published: February 2021

We report analytical expressions for optical forces acting on particles inside waveguides. The analysis builds on our previously reported Fourier Transform method to obtain Beam Shape Coefficients for any beam. Here we develop analytical expressions for the Beam Shape Coefficients in cylindrical and rectangular metallic waveguides. The theory is valid for particle radius a ranging from the Rayleigh regime to large microparticles, such as aerosols like virus loaded droplets. The theory is used to investigate how optical forces within hollow waveguides can be used to sort particles in “optical chromatography” experiments in which particles are optically propelled along a hollow-core waveguide. For Rayleigh particles, the axial force is found to scale with a6, while the radial force, which prevents particles from crashing into the waveguide walls, scales with a3. For microparticles, narrow Mie resonances create a strong wavelength dependence of the optical force, enabling more selective sorting. Several beam parameters, such as power, wavelength, polarization state and waveguide modes can be tuned to optimize the sorting performance. The analysis focuses on cylindrical waveguides, where meter-long liquid waveguides in the form of hollow-core photonic crystal fibers are readily available. The modes of such fibers are well-approximated by the cylindrical waveguide modes considered in the theory.
Isolation and Contact Tracing Can Tip the Scale to Containment of COVID-19 in Populations With Social Distancing
Authors: Kretzschmar Mirjam E. , Rozhnova Ganna , van Boven Michiel
Published: February 2021

SARS-CoV-2 has established itself in all parts of the world, and many countries have implemented social distancing as a measure to prevent overburdening of health care systems. Here we evaluate whether and under which conditions containment of SARS-CoV-2 is possible by isolation and contact tracing in settings with various levels of social distancing. To this end we use a branching process model in which every person generates novel infections according to a probability distribution that is affected by the incubation period distribution, distribution of the latent period, and infectivity. The model distinguishes between household and non-household contacts. Social distancing may affect the numbers of the two types of contacts differently, for example while work and school contacts are reduced, household contacts may remain unchanged. The model allows for an explicit calculation of the basic and effective reproduction numbers, and of exponential growth rates and doubling times. Our findings indicate that if the proportion of asymptomatic infections in the model is larger than 30%, contact tracing and isolation cannot achieve containment for a basic reproduction number (ℛ0) of 2.5. Achieving containment by social distancing requires a reduction of numbers of non-household contacts by around 90%. If containment is not possible, at least a reduction of epidemic growth rate and an increase in doubling time may be possible. We show for various parameter combinations how growth rates can be reduced and doubling times increased by contact tracing. Depending on the realized level of contact reduction, tracing and isolation of only household contacts, or of household and non-household contacts are necessary to reduce the effective reproduction number to below 1. In a situation with social distancing, contact tracing can act synergistically to tip the scale toward containment. These measures can therefore be a tool for controlling COVID-19 epidemics as part of an exit strategy from lock-down measures or for preventing secondary waves of COVID-19.
New Insights Into the Regulation of Lipoprotein Metabolism by PCSK9: Lessons From Stable Isotope Tracer Studies in Human Subjects
Authors: Ying Qidi , Chan Dick C. , Watts Gerald F.
Published: February 2021

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a convertase enzyme mostly produced by the liver. It is a key regulator of LDL metabolism because of its ability to enhance degradation of the LDL receptor. PCSK9 also regulates the metabolism of lipoprotein(a) [Lp(a)] and triglyceride-rich lipoproteins (TRLs). Its key role in modulating atherosclerotic cardiovascular disease (ASCVD) is supported by genetic studies and clinical outcome trials. Kinetic studies provide mechanistic insight into the role of PCSK9 in regulating the physiology and pathophysiology of plasma lipids and lipoproteins. Kinetic data have demonstrated that plasma PCSK9 concentration is inversely associated with the clearance of LDL in men. Gain-of-function mutations of PCSK9 markedly increase plasma LDL-cholesterol concentrations due to impaired LDL-apoB catabolism. Conversely, PCSK9 deficiency results in low LDL-cholesterol associated with enhanced LDL-apoB clearance. Inhibition of PCSK9 with monoclonal antibodies (such as evolocumab or alirocumab) lowers plasma LDL-cholesterol and apoB levels chiefly by upregulating the catabolism of LDL particles in healthy individuals. As monotherapy, PCSK9 inhibitor reduced Lp(a) concentrations by decreasing the production rate. However, as combination therapy, it reduced the plasma concentration of Lp(a) by increasing the fractional catabolism of Lp(a) particles. In statin-treated patients with high Lp(a), PCSK9 inhibition lowers plasma Lp(a) concentrations by accelerating the catabolism of Lp(a) particles. The effect of PCSK9 inhibition on TRL metabolism has been studied in healthy individuals and in patients with type 2 diabetes. These findings suggest that PCSK9 appears to play a less important role in TRL than LDL metabolism. Kinetic studies of PCSK9 inhibition therapy on lipoprotein metabolism in diverse high risk patient populations (such as familial hypercholesterolemia) and new therapeutic combination also merit further investigation.
Mechanisms of Waterlogging Tolerance in Plants: Research Progress and Prospects
Authors: Pan Jiawei , Sharif Rahat , Xu Xuewen , Chen Xuehao
Published: February 2021

Waterlogging is one of the main abiotic stresses suffered by plants. Inhibition of aerobic respiration during waterlogging limits energy metabolism and restricts growth and a wide range of developmental processes, from seed germination to vegetative growth and further reproductive growth. Plants respond to waterlogging stress by regulating their morphological structure, energy metabolism, endogenous hormone biosynthesis, and signaling processes. In this updated review, we systematically summarize the changes in morphological structure, photosynthesis, respiration, reactive oxygen species damage, plant hormone synthesis, and signaling cascades after plants were subjected to waterlogging stress. Finally, we propose future challenges and research directions in this field.
Media Exposure to COVID-19 Predicted Acute Stress: A Moderated Mediation Model of Intolerance of Uncertainty and Perceived Social Support
Authors: He Xiangcai , Zhang Yu , Chen Meng , Zhang Jihong , Zou Weixing , Luo Yu
Published: February 2021

Background: Previous studies have found that disaster-related media exposure could predict acute stress responses. However, few studies have investigated the relationship between media exposure to COVID-19 and acute stress, and less is known about the mechanisms that translate media exposure to COVID-19 into acute stress. The current study explored the impact of media exposure to COVID-19 on acute stress, and examined the mediating role of intolerance of uncertainty (IU) and the moderating role of perceived social support (PSS).

Methods: A total of 1,483 Chinese participants (Mage = 27.93 years, SD = 8.45) completed anonymous online questionnaires regarding media exposure to COVID-19, IU, PSS, and acute stress during the COVID-19 outbreak in China.

Results: Media exposure to COVID-19 was positively related to acute stress, and IU partially mediated this relationship. The direct effect of media exposure to COVID-19 on acute stress, and the relationship between IU and acute stress, were both moderated by PSS. The impacts of both media exposure to COVID-19 and IU on acute stress were stronger for individuals with low PSS.

Limitations: This study collected data in a shorter timeframe, and no assessments occurred during the follow-up, which may prevent us from detecting the changes of the relationships between variables over time. Meanwhile, the self-report method limited the validity of the data due to subjective reporting bias.

Conclusions: These findings contribute to a better understanding of how and when pandemic-related media exposure affects acute stress, and provide new perspectives for the prevention to reduce psychological problems following traumatic events.
The Impacts of SARS-CoV-2 Pandemic on Suicide: A Lexical Analysis
Authors: Gonçalves Júnior Jucier , Sales Jair Paulino de , Moreno Marcial Moreira , Rolim-Neto Modesto Leite
Published: February 2021

Background: Although COVID-19 is a public health emergency, its consequences for the mental health of the population are still scarce. Likewise, its impact on critical situations such as suicide is still poorly explored in the literature. Therefore, this study aimed to analyze in a pioneering way, through lexical and content analysis techniques, the possible impacts of the new COVID-19 pandemic on suicide behavior.

Methods: A lexical analysis, whose sample (not probabilistic, i.e., for convenience) was made up of full-length papers (abstracts) and short communications, about suicide behavior in COVID-19 pandemic, in PubMed and Virtual Health Library (VHL) was carried out following a lexical and content analysis using the software IRaMuTeQ, version 0.7 alpha 2.

Results: The most frequent active words were suicide behavior (n = 649), covid (n = 439), health (n = 358), mental (n = 268), and social (n = 220). Four lexical classes were found and organized into two large groups: the first group, formed by the classes 2 (“methods for psychological treatment”) and 3 (“strategies to minimize the COVID-19 impacts”), was the most representative, totaling 50.6% of the text segments and second group formed by classes 1 (“signs of clinical depression”) and 4 (“COVID-19 pandemic as a public health problem”) with 49.4% of the text segments.

Conclusion: Facing suicide behavior, the direct effects of the COVID-19 pandemic, and the negative feelings and trigger of previous psychiatric illnesses; the measures to deal with the pandemic such as social isolation, decrease in the number of professionals, the opening hours of health establishments, and decrease in the demand for medications; and competing phenomena such as the spread of fake news and lack of empathy are aggressive and potentiating factors of suicidal ideation.
Can ACE2 Receptor Polymorphism Predict Species Susceptibility to SARS-CoV-2?
Authors: Devaux Christian A. , Pinault Lucile , Osman Ikram Omar , Raoult Didier
Published: February 2021

A novel severe acute respiratory syndrome coronavirus, SARS-CoV-2, emerged in China in December 2019 and spread worldwide, causing more than 1.3 million deaths in 11 months. Similar to the human SARS-CoV, SARS-CoV-2 shares strong sequence homologies with a sarbecovirus circulating inRhinolophus affinisbats. Because bats are expected to be able to transmit their coronaviruses to intermediate animal hosts that in turn are a source of viruses able to cross species barriers and infect humans (so-called spillover model), the identification of an intermediate animal reservoir was the subject of intense researches. It was claimed that a reptile (Ophiophagus hannah) was the intermediate host. This hypothesis was quickly ruled out and replaced by the pangolin (Manis javanica) hypothesis. Yet, pangolin was also recently exonerated from SARS-CoV-2 transmission to humans, leaving other animal species as presumed guilty. Guided by the spillover model, several laboratories investigatedin silicothe species polymorphism of the angiotensin I converting enzyme 2 (ACE2) to find the best fits with the SARS-CoV-2 spike receptor-binding site. Following the same strategy, we used multi-sequence alignment, 3-D structure analysis, and electrostatic potential surface generation of ACE2 variants to predict their binding capacity to SARS-CoV-2. We report evidence that such simplein silicoinvestigation is a powerful tool to quickly screen which species are potentially susceptible to SARS-CoV-2. However, possible receptor binding does not necessarily lead to successful replication in host. Therefore, we also discuss here the limitations of thesein silicoapproaches in our quest on the origins of COVID-19 pandemic.