bluuebunny/crossref_metadata_2025 huggingface dataset:
Blocking Ocular Sympathetic Activity Inhibits Choroidal Neovascularization
Authors: Martinez-Camarillo Juan Carlos , Spee Christine K. , Trujillo-Sanchez Gloria Paulina , Rodriguez Anthony , Hinton David R. , Giarola Alessandra , Pikov Victor , Sridhar Arun , Humayun Mark S. , Weitz Andrew C.
Published: January 2022

Purpose: To investigate how modulating ocular sympathetic activity affects progression of choroidal neovascularization (CNV), a hallmark feature of wet age-related macular degeneration (AMD).

Methods: In the first of two studies, Brown Norway rats underwent laser-induced CNV and were assigned to one of the following groups: daily eye drops of artificial tears (n = 10; control group); daily eye drops of the β-adrenoreceptor agonist isoproterenol (n = 10); daily eye drops of the β-adrenoreceptor antagonist propranolol (n = 10); sympathetic internal carotid nerve (ICN) transection 6 weeks prior to laser-induced CNV (n = 10). In the second study, rats underwent laser-induced CNV followed by ICN transection at different time points: immediately after the laser injury (n = 6), 7 days after the laser injury (n = 6), and sham surgery 7 days after the laser injury (n = 6; control group). All animals were euthanized 14 days after laser application. CNV development was quantified with fluorescein angiography and optical coherence tomography (in vivo), as well as lesion volume analysis using 3D confocal reconstruction (postmortem). Angiogenic growth factor protein levels in the choroid were measured with ELISA.

Results: In the first study, blocking ocular sympathetic activity through pharmacological or surgical manipulation led to a 75% or 70% reduction in CNV lesion volume versus the control group, respectively (P < 0.001). Stimulating ocular sympathetic activity with isoproterenol also led to a reduction in lesion volume, but only by 27% versus controls (P < 0.05). VEGF protein levels in the choroid were elevated in the three treatment groups (P < 0.01). In the second study, fluorescein angiography and CNV lesion volume analysis indicated that surgically removing the ocular sympathetic supply inhibited progression of laser-induced CNV, regardless of whether ICN transection was performed on the same day or 7 days after the laser injury.

Conclusion: Surgical and pharmacological block of ocular sympathetic activity can inhibit progression of CNV in a rat model. Therefore, electrical block of ICN activity could be a potential bioelectronic medicine strategy for treating wet AMD.
Complication Differences Between the Tumescent and Non-Tumescent Dissection Techniques for Mastectomy: A Meta-Analysis
Authors: Yang Yi , Zhu Juanying , Qian Xinghua , Feng Jingying , Sun Fukun
Published: January 2022

Purpose

We conducted a systematic literature search and pooled data from studies to compare the incidence of complications between the tumescent and non-tumescent techniques for mastectomy.

Methods

We searched PubMed, Embase, BioMed Central, Ovid, and CENTRAL databases for studies comparing the two mastectomy techniques up to November 1st, 2020. We used a random-effects model to calculate odds ratios (OR) with 95% confidence intervals (CI).

Results

Nine studies were included with one randomized controlled trial (RCT). Meta-analysis indicated no statistically significant difference in the incidence of total skin necrosis (OR 1.18 95% CI 0.71, 1.98 I2 = 82% p=0.52), major skin necrosis (OR 1.58 95% CI 0.69, 3.62 I2 = 71% p=0.28), minor skin necrosis (OR 1.11 95% CI 0.43, 2.85 I2 = 72% p=0.83), hematoma (OR 1.19 95% CI 0.80, 1.79 I2 = 4% p=0.39), and infections (OR 0.87 95% CI 0.54, 1.40 I2 = 54% p=0.56) between tumescent and non-tumescent groups. Analysis of studies using immediate alloplastic reconstruction revealed no statistically significant difference in the incidence of explantation between the two groups (OR 0.78 95% CI 0.46, 1.34 I2 = 62% p=0.37). Multivariable-adjusted ORs on total skin necrosis were available from three studies. Pooled analysis indicated no statistically significant difference between tumescent and non-tumescent groups (OR 1.72 95% CI 0.72, 4.13 I2 = 87% p=0.23).

Conclusion

Low-quality evidence derived mostly from non-randomized studies is indicative of no difference in the incidence of skin necrosis, hematoma, seroma, infection, and explantation between the tumescent and non-tumescent techniques of mastectomy. There is a need for high-quality RCTs to further strengthen the evidence.
Cost-Effectiveness Analysis of Imaging Modalities for Breast Cancer Surveillance Among BRCA1/2 Mutation Carriers: A Systematic Review
Authors: Li Jiaxin , Jia Ziqi , Zhang Menglu , Liu Gang , Xing Zeyu , Wang Xin , Huang Xin , Feng Kexin , Wu Jiang , Wang Wenyan , Wang Jie , Liu Jiaqi , Wang Xiang
Published: January 2022

Background

BRCA1/2 mutation carriers are suggested with regular breast cancer surveillance screening strategies using mammography with supplementary MRI as an adjunct tool in Western countries. From a cost-effectiveness perspective, however, the benefits of screening modalities remain controversial among different mutated genes and screening schedules.

Methods

We searched the MEDLINE/PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases to collect and compare the results of different cost-effectiveness analyses. A simulated model was used to predict the impact of screening strategies in the target group on cost, life-year gained, quality-adjusted life years, and incremental cost-effectiveness ratio (ICER).

Results

Nine cost-effectiveness studies were included. Combined mammography and MRI strategy is cost-effective in BRCA1 mutation carriers for the middle-aged group (age 35 to 54). BRCA2 mutation carriers are less likely to benefit from adjunct MRI screening, which implies that mammography alone would be sufficient from a cost-effectiveness perspective, regardless of dense breast cancer.

Conclusions

Precision screening strategies among BRCA1/2 mutation carriers should be conducted according to the acceptable ICER, i.e., a combination of mammography and MRI for BRCA1 mutation carriers and mammography alone for BRCA2 mutation carriers.

Systematic Review Registration

PROSPERO, identifier CRD42020205471.
Targeting KRAS in Non-Small Cell Lung Cancer
Authors: Corral de la Fuente Elena , Olmedo Garcia Maria Eugenia , Gomez Rueda Ana , Lage Yolanda , Garrido Pilar
Published: January 2022

Kirsten Rat Sarcoma viral oncogene homolog (KRAS) is the most frequently altered oncogene in Non-Small Cell Lung Cancer (NSCLC). KRAS mutant tumors constitute a heterogeneous group of diseases, different from other oncogene-derived tumors in terms of biology and response to treatment, which hinders the development of effective drugs against KRAS. Therefore, for decades, despite enormous efforts invested in the development of drugs aimed at inhibiting KRAS or its signaling pathways, KRAS was considered to be undruggable. Recently, the discovery of a new pocket under the effector binding switch II region of KRAS G12C has allowed the development of direct KRAS inhibitors such as sotorasib, the first FDA-approved drug targeting KRAS G12C, or adagrasib, initiating a new exciting era. However, treatment with targeted KRAS G12C inhibitors also leads to resistance, and understanding the possible mechanisms of resistance and which drugs could be useful to overcome it is key. Among others, KRAS G12C (ON) tricomplex inhibitors and different combination therapy strategies are being analyzed in clinical trials. Another area of interest is the potential role of co-mutations in treatment selection, particularly immunotherapy. The best first-line strategy remains to be determined and, due to the heterogeneity of KRAS, is likely to be based on combination therapies.
Participation and Yield of a Lung Cancer Screening Program in Hebei, China
Authors: Liang Di , Shi Jin , Li Daojuan , Wu Siqi , Jin Jing , He Yutong
Published: January 2022

Objective

Lung cancer screening has been widely conducted in Western countries. However, population-based lung cancer screening programs in Hebei in China are sparse. Our study aimed to assess the participation rate and detection rate of positive nodules and lung cancer in Hebei province.

Method

In total, 228 891 eligible participants aged 40–74 years were enrolled in the Cancer Screening Program in Hebei from 2013 to 2019. A total of 54 846 participants were evaluated as the lung cancer high-risk population by a risk score system which basically followed the Harvard Risk Index and was adjusted for the characteristics of the Chinese population. Then this high-risk population was recommended for low-dose computed tomography (LDCT) screening. And all participants attended annual passive follow-up, and the active follow-up interval was based on radiologist’s suggestion. All participants were followed-up until December 31, 2020. The overall, group-specific participation rates were calculated, and its associated factors were analyzed by a multivariable logistic regression model. Participation rates and detection of positive nodules and lung cancer were reported.

Results

The overall participation rate was 52.69%, where 28 899 participants undertook LDCT screening as recommended. The multivariable logistic regression model demonstrated that a high level of education, having disease history, and occupational exposure were found to be associated with the participation in LDCT screening. The median follow-up time was 3.56 person-years. Overall, the positive identification of lung nodules and suspected lung cancer were 12.73% and 1.46% through LDCT screening. After the native and passive follow-up, 257 lung cancer cases were diagnosed by lung cancer screening, and the detection rate of lung cancer was 0.89% in the screening group. And its incidence density was 298.72 per 100,000. Positive lung nodule rate and detection rate were increased with age.

Conclusion

Our study identified personal and epidemiological factors that could affect the participation rate. Our findings could provide the guideline for precise prevention and control of lung cancer in the future.
Twenty Years On: RECIST as a Biomarker of Response in Solid Tumours an EORTC Imaging Group – ESOI Joint Paper
Authors: Fournier Laure , de Geus-Oei Lioe-Fee , Regge Daniele , Oprea-Lager Daniela-Elena , D’Anastasi Melvin , Bidaut Luc , Bäuerle Tobias , Lopci Egesta , Cappello Giovanni , Lecouvet Frederic , Mayerhoefer Marius , Kunz Wolfgang G. , Verhoeff Joost J. C. , Caruso Damiano , Smits Marion , Hoffmann Ralf-Thorsten , Gourtsoyianni Sofia , Beets-Tan Regina , Neri Emanuele , deSouza Nandita M. , Deroose Christophe M. , Caramella Caroline
Published: January 2022

Response evaluation criteria in solid tumours (RECIST) v1.1 are currently the reference standard for evaluating efficacy of therapies in patients with solid tumours who are included in clinical trials, and they are widely used and accepted by regulatory agencies. This expert statement discusses the principles underlying RECIST, as well as their reproducibility and limitations. While the RECIST framework may not be perfect, the scientific bases for the anticancer drugs that have been approved using a RECIST-based surrogate endpoint remain valid. Importantly, changes in measurement have to meet thresholds defined by RECIST for response classification within thus partly circumventing the problems of measurement variability. The RECIST framework also applies to clinical patients in individual settings even though the relationship between tumour size changes and outcome from cohort studies is not necessarily translatable to individual cases. As reproducibility of RECIST measurements is impacted by reader experience, choice of target lesions and detection/interpretation of new lesions, it can result in patients changing response categories when measurements are near threshold values or if new lesions are missed or incorrectly interpreted. There are several situations where RECIST will fail to evaluate treatment-induced changes correctly; knowledge and understanding of these is crucial for correct interpretation. Also, some patterns of response/progression cannot be correctly documented by RECIST, particularly in relation to organ-site (e.g. bone without associated soft-tissue lesion) and treatment type (e.g. focal therapies). These require specialist reader experience and communication with oncologists to determine the actual impact of the therapy and best evaluation strategy. In such situations, alternative imaging markers for tumour response may be used but the sources of variability of individual imaging techniques need to be known and accounted for. Communication between imaging experts and oncologists regarding the level of confidence in a biomarker is essential for the correct interpretation of a biomarker and its application to clinical decision-making. Though measurement automation is desirable and potentially reduces the variability of results, associated technical difficulties must be overcome, and human adjudications may be required.
The Development of Single-Cell Metabolism and Its Role in Studying Cancer Emergent Properties
Authors: Wei Dingju , Xu Meng , Wang Zhihua , Tong Jingjing
Published: January 2022

Metabolic reprogramming is one of the hallmarks of malignant tumors, which provides energy and material basis for tumor rapid proliferation, immune escape, as well as extensive invasion and metastasis. Blocking the energy and material supply of tumor cells is one of the strategies to treat tumor, however tumor cell metabolic heterogeneity prevents metabolic-based anti-cancer treatment. Therefore, searching for the key metabolic factors that regulate cell cancerous change and tumor recurrence has become a major challenge. Emerging technology––single-cell metabolomics is different from the traditional metabolomics that obtains average information of a group of cells. Single-cell metabolomics identifies the metabolites of single cells in different states by mass spectrometry, and captures the molecular biological information of the energy and substances synthesized in single cells, which provides more detailed information for tumor treatment metabolic target screening. This review will combine the current research status of tumor cell metabolism with the advantages of single-cell metabolomics technology, and explore the role of single-cell sequencing technology in searching key factors regulating tumor metabolism. The addition of single-cell technology will accelerate the development of metabolism-based anti-cancer strategies, which may greatly improve the prognostic survival rate of cancer patients.
Bioinspired Membrane-Coated Nanoplatform for Targeted Tumor Immunotherapy
Authors: Mu Dan , He Pan , Shi Yesi , Jiang Lai , Liu Gang
Published: January 2022

Immunotherapy can effectively activate the immune system and reshape the tumor immune microenvironment, which has been an alternative method in cancer therapy besides surgery, radiotherapy, and chemotherapy. However, the current clinical outcomes are not satisfied due to the lack of targeting of the treatment with some unexpected damages to the human body. Recently, cell membrane-based bioinspired nanoparticles for tumor immunotherapy have attracted much attention because of their superior immune regulating, drug delivery, excellent tumor targeting, and biocompatibility. Together, the article reviews the recent progress of cell membrane-based bioinspired nanoparticles for immunotherapy in cancer treatment. We also evaluate the prospect of bioinspired nanoparticles in immunotherapy for cancer. This strategy may open up new research directions for cancer therapy.
Proposing a Neurotropic Etiology for Acute Posterior Multifocal Placoid Pigment Epitheliopathy and Relentless Placoid Chorioretinitis
Authors: Steptoe Paul J. , Pearce Ian , Beare Nicholas A.V. , Sreekantam Sreekanth , Mohammed Bashar R. , Barry Robert J. , Steeples Laura R. , Denniston Alastair K. , Murray Philip I.
Published: January 2022

Purpose

To reassess the underlying pathophysiology of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and relentless placoid chorioretinitis (RPC) through comparison with the non-inoculated eye of the von Szily animal model of neurotropic viral retinal infection.

Methods

Narrative review.

Results

Literature reports of isolated neurotropic viral entities and rising serological viral titers in APMPPE after presentation support a potential direct infective etiology. In general, viral transport along axons results in mitochondrial stasis and disruption of axoplasmic flow. Clinical manifestations of axoplasmic flow disruption in APMPPE/RPC may signify the passage of virus along the neuronal pathway. From a case series of 11 patients, we demonstrate a timely, spatial, and proportional association of optic disc swelling with APMPPE lesion occurrence. Signs within the inner retina appear to precede outer retinal lesions; and acute areas of outer nuclear layer (ONL) hyperreflectivity appear to be the result of coalescence of multiple hyperreflective foci resembling axonal spheroids (which occur as a consequence of axoplasmic disruption) and follow the Henle fiber layer neurons. Underlying areas of retinal pigment epithelium (RPE) hyper-autofluorescence follow ONL hyperreflectivity and may signify localized infection. Areas of apparent choriocapillaris hypoperfusion mirror areas of RPE/Bruch’s membrane separation and appear secondary to tractional forces above. Increases in choroidal thickness with lesion occurrence and focal areas of choriocapillaris hypoperfusion are observed in both APMPPE/RPC and the von Szily model.

Conclusions

The neurotrophic infection model provides significant advantages over the existing primary choriocapillaris ischemia hypothesis to account for the range of imaging signs observed in APMPPE and RPC.
Immunosuppressive Isopimarane Diterpenes From Cultures of the Endophytic Fungus Ilyonectria robusta
Authors: Ye Ke , Lv Xiao , Zhang Xian , Wei Pan-Pan , Li Zheng-Hui , Ai Hong-Lian , Zhao Da-Ke , Liu Ji-Kai
Published: January 2022

Five new isopimarane diterpenes, robustaditerpene A-E (1–5), which include 19-nor-isopimarane skeleton and isopimarane skeleton, were isolated from the liquid fermentation of the endophytic fungus Ilyonectria robusta collected from Bletilla striata. The structure elucidation and relative configuration assignments of all compounds were accomplished by interpretation of NMR and HRESIMS spectrometric analyses and 13C NMR calculation. And the absolute configuration of 1-5 were identified by single-crystal X-ray diffraction and ECD calculation. Compound 3 inhibited lipopolysaccharide-induced B lymphocytes cell proliferation with an IC50 value at 17.42 ± 1.57 μM while compound 5 inhibited concanavalin A-induced T lymphocytes cell proliferation with an IC50 value at 75.22 ± 6.10 μM. These data suggested that compounds 3 and 5 may possess potential immunosuppressive prospect.
Treating Rare Diseases in Africa: The Drugs Exist but the Need Is Unmet
Authors: Luzzatto Lucio , Makani Julie
Published: January 2022

Rare diseases (RD) pose serious challenges in terms of both diagnosis and treatment. Legislation was passed in the US (1983) and in EU (2000) aimed to reverse the previous neglect of RD, by providing incentives for development of “orphan drugs” (OD) for their management. Here we analyse the current situation in Africa with respect to (1) sickle cell disease (SCD), that qualifies as rare in the US and in EU, but is not at all rare in African countries (frequencies up to 1–2%); (2) paroxysmal nocturnal haemoglobinuria (PNH), that is ultra-rare in Africa as everywhere else (estimated <10 per million). SCD can be cured by bone marrow transplantation and recently by gene therapy, but very few African patients have access to these expensive procedures; on the other hand, the disease-ameliorating agent hydroxyurea is not expensive, but still the majority of patients in Africa are not receiving it. For PNH, currently most patients In high income countries are treated with a highly effective OD that costs about $400,000 per year per patient: this is not available in Africa. Thus, the impact of OD legislation has been practically nil in this continent. As members of the medical profession and of the human family, we must aim to remove barriers that are essentially financial: especially since countries with rich economies share a history of having exploited African countries. We call on the Global Fund to supply hydroxyurea for all SCD patients; and we call on companies who produce ODs to donate, for every patient who receives an expensive OD in a high income country, enough of the same drug, at a symbolic price, to treat one patient in Africa.
Hsp47 Inhibitor Col003 Attenuates Collagen-Induced Platelet Activation and Cerebral Ischemic–Reperfusion Injury in Rats
Authors: Wu Shuang , Liang Chengwei , Xie Xiaoyun , Huang Haiping , Fu Jinfeng , Wang Cilan , Su Zhiheng , Wang Youqiong , Qu Xiang , Li Jinpin , Liu Jingli
Published: January 2022

Ischemic stroke is a major type of stroke worldwide currently without effective treatment, although antiplatelet therapy is an existing option for it. In previous studies, heat shock protein 47 (Hsp47) was found to be expressed on the surface of human and mice platelets and to strengthen the interaction between platelets and collagen. In recent years, Col003 was discovered to inhibit the interaction of Hsp47 with collagen. We evaluated whether the Hsp47 inhibitor Col003 is a promising therapeutic agent for ischemic stroke. Here, we first verified that Hsp47 is also expressed on the surface of rat platelets, and its inhibitor Col003 significantly inhibited thrombus formation in the FeCl3-induced rat carotid arterial thrombus model. Both Col003 and clopidogrel did not alter the bleeding time or coagulation parameters, while aspirin increased the tail-bleeding time (p < 0.05). The low cytotoxicity level of Col003 to rat platelets and human liver cells was similar to those of aspirin and clopidogrel. Col003 inhibited collagen-induced platelet aggregation, adhesion, [Ca2+]i mobilization, P-selectin expression, reactive oxygen species production and the downstream signal pathway of collagen receptors. The results of the middle cerebral artery occlusion model indicated that Col003 has a protective effect against cerebral ischemic–reperfusion injury in rats. The Hsp47 inhibitor Col003 exerted antiplatelet effect and protective effect against brain damage induced by ischemic stroke through the inhibition of glycoprotein VI (GPVI)and mitogen-activated protein kinase (MAPK) signaling events, which might yield a new antiplatelet agent and strategy to treat ischemic stroke.
Intracellular Reduction-Responsive Molecular Targeted Nanomedicine for Hepatocellular Carcinoma Therapy
Authors: Ding Lei , Zhang Ping , Huang Xu , Yang Kunmeng , Liu Xingkai , Yu Zhenxiang
Published: January 2022

The stimuli-responsive polymer-based platform for controlled drug delivery has gained increasing attention in treating hepatocellular carcinoma (HCC) owing to the fascinating biocompatibility and biodegradability, improved antitumor efficacy, and negligible side effects recently. Herein, a disulfide bond-contained polypeptide nanogel, methoxy poly(ethylene glycol)−poly(l-phenylalanine-co-l-cystine) [mPEG−P(LP-co-LC)] nanogel, which could be responsive to the intracellular reduction microenvironments, was developed to deliver lenvatinib (LEN), an inhibitor of multiple receptor tyrosine kinases, for HCC therapy. The lenvatinib-loaded nanogel (NG/LEN) displayed concise drug delivery under the stimulus of glutathione in the cancer cells. Furthermore, the intracellular reduction-responsive nanomedicine NG/LEN showed excellent antitumor effect and almost no side effects toward both subcutaneous and orthotopic HCC tumor-allografted mice in comparison to free drug. The excellent tumor-inhibition efficacy with negligible side effects demonstrated the potential of NG/LEN for clinical molecular targeted therapy of gastrointestinal carcinoma in the future.
The Action of 2-Aminoethyldiphenyl Borinate on the Pulmonary Arterial Hypertension and Remodeling of High-Altitude Hypoxemic Lambs
Authors: Castillo-Galán Sebastián , Parrau Daniela , Hernández Ismael , Quezada Sebastián , Díaz Marcela , Ebensperger Germán , Herrera Emilio A. , Moraga Fernando A. , Iturriaga Rodrigo , Llanos Aníbal J. , Reyes Roberto V.
Published: January 2022

Calcium signaling is key for the contraction, differentiation, and proliferation of pulmonary arterial smooth muscle cells. Furthermore, calcium influx through store-operated channels (SOCs) is particularly important in the vasoconstrictor response to hypoxia. Previously, we found a decrease in pulmonary hypertension and remodeling in normoxic newborn lambs partially gestated under chronic hypoxia, when treated with 2-aminoethyldiphenyl borinate (2-APB), a non-specific SOC blocker. However, the effects of 2-APB are unknown in neonates completely gestated, born, and raised under environmental hypoxia. Accordingly, we studied the effects of 2-APB-treatment on the cardiopulmonary variables in lambs under chronic hypobaric hypoxia. Experiments were done in nine newborn lambs gestated, born, and raised in high altitude (3,600 m): five animals were treated with 2-APB [intravenous (i.v.) 10 mg kg–1] for 10 days, while other four animals received vehicle. During the treatment, cardiopulmonary variables were measured daily, and these were also evaluated during an acute episode of superimposed hypoxia, 1 day after the end of the treatment. Furthermore, pulmonary vascular remodeling was assessed by histological analysis 2 days after the end of the treatment. Basal cardiac output and mean systemic arterial pressure (SAP) and resistance from 2-APB- and vehicle-treated lambs did not differ along with the treatment. Mean pulmonary arterial pressure (mPAP) decreased after the first day of 2-APB treatment and remained lower than the vehicle-treated group until the third day, and during the fifth, sixth, and ninth day of treatment. The net mPAP increase in response to acute hypoxia did not change, but the pressure area under the curve (AUC) during hypoxia was slightly lower in 2-APB-treated lambs than in vehicle-treated lambs. Moreover, the 2-APB treatment decreased the pulmonary arterial wall thickness and the α-actin immunoreactivity and increased the luminal area with no changes in the vascular density. Our findings show that 2-APB treatment partially reduced the contractile hypoxic response and reverted the pulmonary vascular remodeling, but this is not enough to normalize the pulmonary hemodynamics in chronically hypoxic newborn lambs.
Differential Network Testing Reveals Diverging Dynamics of Organ System Interactions for Survivors and Non-survivors in Intensive Care Medicine
Authors: Schefzik Roman , Boland Leonie , Hahn Bianka , Kirschning Thomas , Lindner Holger A. , Thiel Manfred , Schneider-Lindner Verena
Published: January 2022

Statistical network analyses have become popular in many scientific disciplines, where an important task is to test for differences between two networks. We describe an overall framework for differential network testing procedures that vary regarding (1) the network estimation method, typically based on specific concepts of association, and (2) the network characteristic employed to measure the difference. Using permutation-based tests, our approach is general and applicable to various overall, node-specific or edge-specific network difference characteristics. The methods are implemented in our freely available R software package DNT, along with an R Shiny application. In a study in intensive care medicine, we compare networks based on parameters representing main organ systems to evaluate the prognosis of critically ill patients in the intensive care unit (ICU), using data from the surgical ICU of the University Medical Centre Mannheim, Germany. We specifically consider both cross-sectional comparisons between a non-survivor and a survivor group and longitudinal comparisons at two clinically relevant time points during the ICU stay: first, at admission, and second, at an event stage prior to death in non-survivors or a matching time point in survivors. The non-survivor and the survivor networks do not significantly differ at the admission stage. However, the organ system interactions of the survivors then stabilize at the event stage, revealing significantly more network edges, whereas those of the non-survivors do not. In particular, the liver appears to play a central role for the observed increased connectivity in the survivor network at the event stage.
Improved Ablation Efficiency in PVI Guided by Contact Force and Local Impedance: Chronic Canine Model
Authors: Gutbrod Sarah R. , Shuros Allan , Koya Vijay , Alexander-Curtis Michelle , Lehn Lauren , Miklos Kimberly , Mounsey John Paul , Meyers Jason D.
Published: January 2022

Background: The purpose of this study was to assess the effect local impedance (LI) has on an ablation workflow when combined with a contact force (CF) ablation catheter.

Methods: Left pulmonary vein isolation was performed in an in vivo canine model (N = 8) using a nominal (30 W) or an elevated (50 W) power strategy with a CF catheter. The catheter was enabled to measure LI prior to and during ablation. LI was visible for only one of the vein isolations.

Results: Chronic block was achieved in all animals when assessed 30 ± 5 days post-ablation procedure with a median LI drop during RF ranging from 23.0 to 34.0 Ω. In both power cohorts, the median radiofrequency (RF) duration decreased if LI was visible to the operator (30 W only CF: 17.0 s; 30 W CF + LI: 14.0 s, p = 0.009; 50 W only CF: 6.0 s; 50 W CF + LI: 4.0 s, p = 0.019). An inverse relationship between the LI prior to RF delivery and the RF duration required to achieve an effective lesion was observed. There was no correlation between the magnitude of the applied force and the drop in LI, once at least 5 g was achieved.

Conclusions: An elevated power strategy with the context of CF and LI led to the most efficient titration of successful RF energy delivery. The combination of feedback allows for customization of the ablation strategy based on local tissue variation rather than a uniform approach that could potentially lead to overtreatment. Higher LI drops were more readily achievable when an elevated power strategy was utilized, especially in conditions where the catheter was coupled against tissue with low resistivity. Clinical study is warranted to determine if there is an additive safety benefit to visualizing the dynamics of the tissue response to RF energy with LI when an elevated power strategy is used.
Post-marathon Decline in Right Ventricular Radial Motion Component Among Amateur Sportsmen
Authors: Lewicka-Potocka Zuzanna , Kaleta-Duss Anna Maria , Lewicka Ewa , Kubik Marcin , Faran Anna , Szymeczko Paweł , Gała̧ska Rafał , Raczak Grzegorz , Da̧browska-Kugacka Alicja
Published: January 2022

Moderate physical activity has a positive impact on health, although extreme forms of sport such as marathon running may trigger exercise-induced cardiac fatigue. The explicit distinction between the right ventricular (RV) physiological response to training and maladaptive remodeling has not yet been determined. In this study, we aimed to analyze the impact of running a marathon on RV mechanics in amateur athletes using three-dimensional (3D) echocardiography (ECHO) and the ReVISION method (RV separate wall motion quantification). A group of 34 men with a mean age of 40 ± 8 years who successfully finished a marathon underwent ECHO three times, i.e., 2 weeks before the marathon (stage I), at the marathon finish line (stage II), and 2 weeks after the marathon (stage III). The ECHO findings were then correlated with the concentrations of biomarkers related to myocardial injury and overload and also obtained at the three stages. On finishing the marathon, the amateur athletes were found to have a significant (p < 0.05) increase in end-diastolic (with a median of 51.4 vs. 57.0 ml/m2) and end-systolic (with a median of 24.9 vs. 31.5 ml/m2) RV volumes indexed to body surface area, reduced RV ejection fraction (RVEF) (with a median of 51.0% vs. 46.0%), and a decrease in RV radial shortening [i.e., radial EF (REF)] (with a mean of 23.0 ± 4.5% vs. 19.3 ± 4.2%), with other RV motion components remaining unchanged. The post-competition decrease in REF was more evident in runners with larger total volume of trainings (R2 = 0.4776, p = 0.0002) and higher concentrations of high-sensitivity cardiac troponin I (r = 0.43, p < 0.05) during the preparation period. The decrease in REF was more prominent in the training of marathoners more than 47 km/week. At stage II, marathoners with a more marked decrease in RVEF and REF had higher galectin-3 (Gal-3) levels (r = −0.48 and r = −0.39, respectively; p < 0.05). Running a marathon significantly altered the RV performance of amateur athletes. Transient impairment in RV systolic function resulted from decreased radial shortening, which appeared in those who trained more extensively. Observed ECHO changes correlated with the concentrations of the profibrotic marker Gal-3.
Interactive Regulation of Hormone and Resistance Gene in Proline Metabolism Is Involved in Effector-Triggered Immunity or Disease Susceptibility in the Xanthomonas campestris pv. campestris–Brassica napus Pathosystem
Authors: Mamun Md Al , Islam Md Tabibul , Lee Bok-Rye , Bae Dong-Won , Kim Tae-Hwan
Published: January 2022

To characterize cultivar variations in hormonal regulation of the transition between pattern-triggered immunity (PTI) and effector-triggered immunity or susceptibility (ETI or ETS), the responses of resistance (R-) genes, hydrogen peroxide, and proline metabolism in two Brassica napus cultivars to contrasting disease susceptibility (resistant cv. Capitol vs. susceptible cv. Mosa) were interpreted as being linked to those of endogenous hormonal levels and signaling genes based on a time course of disease symptom development. Disease symptoms caused by the Xanthomonas campestris pv. campestris (Xcc) infections were much more developed in cv. Mosa than in cv. Capitol, as shown by an earlier appearance (at 3 days postinoculation [3 DPI]) and larger V-shaped necrosis lesions (at 9–15 DPI) in cv. Mosa. The cultivar variations in the R-genes, hormone status, and proline metabolism were found in two different phases (early [0–3 DPI] and later [9–15 DPI]). In the early phase, Xcc significantly upregulated PTI-related cytoplasmic kinase (Botrytis-induced kinase-1 [BIK1]) expression (+6.3-fold) with salicylic acid (SA) accumulation in cv. Capitol, while relatively less (+2.6-fold) with highly increased jasmonic acid (JA) level in cv. Mosa. The Xcc-responsive proline accumulation in both cultivars was similar to upregulated expression of proline synthesis-related genes (P5CS2 and P5CR). During the later phase in cv. Capitol, Xcc-responsive upregulation of ZAR1 (a coiled-coil-nucleotide binding site-leucine-rich repeat [CC-NB-LRR-type R-gene]) was concomitant with a gradual increase in JA levels without additional proline accumulation. However, in cv. Mosa, upregulation of TAO1 (a toll/interleukin-1 receptor-nucleotide binding site-leucine-rich repeat [TIR-NB-LRR-type R-gene]) was consistent with an increase in SA and abscisic acid (ABA) levels and resulted in an antagonistic depression of JA, which led to a proline accumulation. These results indicate that Xcc-induced BIK1- and ZAR1-mediated JA signaling interactions provide resistance and confirm ETI, whereas BIK1- and TAO1-enhanced SA- and/or ABA-mediated proline accumulation is associated with disease susceptibility (ETS).
Modified “Allele-Specific qPCR” Method for SNP Genotyping Based on FRET
Authors: Kalendar Ruslan , Baidyussen Akmaral , Serikbay Dauren , Zotova Lyudmila , Khassanova Gulmira , Kuzbakova Marzhan , Jatayev Satyvaldy , Hu Yin-Gang , Schramm Carly , Anderson Peter A. , Jenkins Colin L. D. , Soole Kathleen L. , Shavrukov Yuri
Published: January 2022

The proposed method is a modified and improved version of the existing “Allele-specific q-PCR” (ASQ) method for genotyping of single nucleotide polymorphism (SNP) based on fluorescence resonance energy transfer (FRET). This method is similar to frequently used techniques like Amplifluor and Kompetitive allele specific PCR (KASP), as well as others employing common universal probes (UPs) for SNP analyses. In the proposed ASQ method, the fluorophores and quencher are located in separate complementary oligonucleotides. The ASQ method is based on the simultaneous presence in PCR of the following two components: an allele-specific mixture (allele-specific and common primers) and a template-independent detector mixture that contains two or more (up to four) universal probes (UP-1 to 4) and a single universal quencher oligonucleotide (Uni-Q). The SNP site is positioned preferably at a penultimate base in each allele-specific primer, which increases the reaction specificity and allele discrimination. The proposed ASQ method is advanced in providing a very clear and effective measurement of the fluorescence emitted, with very low signal background-noise, and simple procedures convenient for customized modifications and adjustments. Importantly, this ASQ method is estimated as two- to ten-fold cheaper than Amplifluor and KASP, and much cheaper than all those methods that rely on dual-labeled probes without universal components, like TaqMan and Molecular Beacons. Results for SNP genotyping in the barley genesHvSAP16andHvSAP8, in which stress-associated proteins are controlled, are presented as proven and validated examples. This method is suitable for bi-allelic uniplex reactions but it can potentially be used for 3- or 4-allelic variants or different SNPs in a multiplex format in a range of applications including medical, forensic, or others involving SNP genotyping.
Regulatory Roles of Small Non-coding RNAs in Sugar Beet Resistance Against Beet curly top virus
Authors: Majumdar Rajtilak , Galewski Paul J. , Eujayl Imad , Minocha Rakesh , Vincill Eric , Strausbaugh Carl A.
Published: January 2022

Beet curly top virus (BCTV) mediated yield loss in sugar beets is a major problem worldwide. The circular single-stranded DNA virus is transmitted by the beet leafhopper. Genetic sources of BCTV resistance in sugar beet are limited and commercial cultivars rely on chemical treatments versus durable genetic resistance. Phenotypic selection and double haploid production have resulted in sugar beet germplasm (KDH13; 13 and KDH4-9; 4) that are highly resistant to BCTV. The molecular mechanism of resistance to the virus is unknown, especially the role of small non-coding RNAs (sncRNAs) during early plant–viral interaction. Using the resistant lines along with a susceptible line (KDH19-17; 19), we demonstrate the role of sugar beet microRNAs (miRNAs) in BCTV resistance during early infection stages when symptoms are not yet visible. The differentially expressed miRNAs altered the expression of their corresponding target genes such as pyruvate dehydrogenase (EL10Ac1g02046), carboxylesterase (EL10Ac1g01087), serine/threonine protein phosphatase (EL10Ac1g01374), and leucine-rich repeats (LRR) receptor-like (EL10Ac7g17778), that were highly expressed in the resistant lines versus susceptible lines. Pathway enrichment analysis of the miRNA target genes showed an enrichment of genes involved in glycolysis/gluconeogenesis, galactose metabolism, starch, and sucrose metabolism to name a few. Carbohydrate analysis revealed altered glucose, galactose, fructose, and sucrose concentrations in the infected leaves of resistant versus susceptible lines. We also demonstrate differential regulation of BCTV derived sncRNAs in the resistant versus susceptible lines that target sugar beet genes such as LRR (EL10Ac1g01206), 7-deoxyloganetic acid glucosyltransferase (EL10Ac5g12605), and transmembrane emp24 domain containing (EL10Ac6g14074) and altered their expression. In response to viral infection, we found that plant derived miRNAs targeted BCTV capsid protein/replication related genes and showed differences in expression among resistant and susceptible lines. The data presented here demonstrate the contribution of miRNA mediated regulation of metabolic pathways and cross-kingdom RNA interference (RNAi) in sugar beet BCTV resistance.
CsWRKY25 Improves Resistance of Citrus Fruit to Penicillium digitatum via Modulating Reactive Oxygen Species Production
Authors: Wang Wenjun , Li Ting , Chen Qi , Yao Shixiang , Deng Lili , Zeng Kaifang
Published: January 2022

WRKY transcription factors (TFs) play crucial roles in the regulation of biotic stress. Citrus is the most productive fruit in the world. It is of great value to investigate the regulatory molecular mechanism of WRKYs in improving disease resistance. In this research, the transcription level of CsWRKY25 was upregulated in P. digitatum infected citrus peel, and CsWRKY25 activated the expression of three target genes (RbohB, RbohD, and PR10). Besides, the Agrobacterium-mediated transient overexpression of CsWRKY25 has also been shown to enhance resistance to P. digitatum in citrus, and caused the accumulation of hydrogen peroxide and lignin. The accumulation of ROS also activated the antioxidant system, the catalase (CAT), peroxidase (POD), and cinnamyl alcohol dehydrogenase (CAD) genes were significant upregulated, leading to activation of antioxidant enzymes. In addition, the up-regulated expression of MPK5 and MPK6 genes suggested that the regulatory role of CsWRKY25 might be related to the phosphorylation process. In conclusion, CsWRKY25 could enhance the resistance to P. digitatum via modulating ROS production and PR genes in citrus peel.
Parent Provision of Choice Is a Key Component of Autonomy Support in Predicting Child Executive Function Skills
Authors: Castelo Romulus J. , Meuwissen Alyssa S. , Distefano Rebecca , McClelland Megan M. , Galinsky Ellen , Zelazo Philip David , Carlson Stephanie M.
Published: January 2022

Although previous work has linked parent autonomy support to the development of children’s executive function (EF) skills, the role of specific autonomy-supportive behaviors has not been thoroughly investigated. We compiled data from four preschool-age samples in the Midwestern United States (N = 366; M age = 44.26 months; 72% non-Hispanic White, 19% Black/African American, 5% Multiracial) to examine three relevant autonomy-supportive behaviors (supporting competence, positive verbalizations, and offering choice) and their associations with child EF. We coded parent autonomy-supportive behaviors from a 10-min interaction between parent and child dyads working on challenging jigsaw puzzles together. Children completed a battery of EF. Overall, child EF was most consistently correlated with the offering choice subscale. Additionally, only the offering choice subscale predicted child EF while controlling for the other autonomy support subscales and child age. These results suggest that parent provision of choice is an especially relevant aspect of autonomy-supportive parenting and may be important to the development of EF in early childhood. Future research should directly measure children’s experience with choice and how it relates to emerging EF.
Effects of Self-Control on Subjective Well-Being: Examining the Moderating Role of Trait and State Motivation
Authors: Zhao Guojun , Xie Fusen , Luo Yuchen , Liu Yixuan , Chong Yuan , Zhang Qi , Wang Wenjie
Published: January 2022

It is well documented that self-control has a positive effect on individuals’ subjective well-being. However, little research has focused on the moderators underlying this relationship. The present research used two studies to examine the moderating role of both trait and state motivation on the relationship between self-control and subjective well-being using psychometric and experimental models, respectively. In Study 1, we explored whether trait motivation (including promotion vs. prevention motivation) moderated the relationship between trait self-control and subjective well-being using a psychometric model. In Study 2, we examined the moderating effects of both trait and state motivation on the effect of state self-control (measured via ego depletion) on subjective well-being using an experimental model. Our results indicated that self-control had a positive effect on subjective well-being, with this relationship being primarily moderated by prevention motivation. When state and trait prevention motivations were congruent, self-control had the most obvious impact on subjective well-being. This study suggests that current understandings around the association between self-control and happiness is limited, implying that motivation should be the focus of future research.
Effect of Alexithymia on Internet Addiction Among College Students: The Mediating Role of Metacognition Beliefs
Authors: Luo Hongge , Zhao Yanli , Hong Jiangyue , Wang Hong , Zhang Xiujun , Tan Shuping
Published: January 2022

Background: Previous studies have found that alexithymia plays an important role in the pathogenesis of Internet addiction. However, the effect of alexithymia on both metacognition and Internet addiction has yet to be examined.

Methods: The Toronto Alexithymia Scale, Metacognition Questionnaire, and Internet Addiction Test were used to assess a sample of 356 college students. A parallel mediator effect analysis was applied to test the hypothesis that metacognition mediates the relationship between alexithymia and Internet addiction.

Results: The parallel multiple mediator models showed that alexithymia predicted the five dimensions of metacognition and Internet addiction, and that three dimensions—cognitive confidence, positive beliefs about worry, and the need to control thoughts—partially mediated this relationship.

Conclusion: Alexithymia could directly and indirectly predict Internet addiction via metacognition.
Personality-Related Determinants of Physical Activity Among Polish and Spanish Physical Education Students
Authors: Gacek Maria , Kosiba Grażyna , Wojtowicz Agnieszka , López Sánchez Guillermo F. , Szalewski Jacek
Published: January 2022

We aimed to analyze personality-related determinants of physical activity among Polish and Spanish physical education (PE) students. The study was conducted among 219 Polish and 280 Spanish PE students, using the International Physical Activity Questionnaire (IPAQ) and the NEO-FFI Personality Inventory. Compared with Spanish PE students, their Polish counterparts are characterized by a higher level of extraversion and conscientiousness and a lower level of neuroticism. The level of total physical activity for all students was 8,697.21 METs, and this value was higher among Polish students. Among Polish and Spanish PE students, the level of total, vigorous, and moderate physical activity increased along with the increase in extraversion, while a decrease occurred along with the increase in neuroticism. The level of each domain of physical activity also increased in line with the intensification of student conscientiousness. In moderation analyses, it was shown that the home country of students may be considered a moderator of the relationship between conscientiousness and total exercise in such a way that the physical activity increased along with the increase in conscientiousness only among the Polish students. In addition, the country is a moderator of the correlation between moderate physical activity and neuroticism (p = 0.031), openness (p = 0.049), and conscientiousness (p = 0.019), with moderate activity only decreasing among Polish students and increasing along with the increase in openness and conscientiousness. Positive correlations among physical activity, extraversion, and conscientiousness, as well as negative ones with neuroticism, were demonstrated among Polish and Spanish students, and also the moderating impact of the country on the correlation between personality-related dimensions and physical activity.