bluuebunny/crossref_metadata_2025 huggingface dataset:
The modified computed tomography severity index combined with low skeletal muscle mass can better predict the severity of hypertriglyceridemia‐induced pancreatitis
Authors: Xu Liuhui , Yu Huajun , Chen Lifang , Xia Weizhi , Shi Liuzhi , Yang Yunjun , Huang Yingbao
Published: June 2022

Background

Body composition parameters are associated with hypertriglyceridemia‐induced pancreatitis (HTGP). This study investigated the association between the quantity of muscle assessed using computed tomography (CT) and the severity of HTGP.

Methods

The modified CT severity index (MCTSI) was calculated from admission examination data. Patients’ characteristics and body composition parameters were collected. Univariate and multivariate logistic regression analyses were also performed. The receiver operating characteristic curves and corresponding area under the curves (AUC) were calculated to test the efficiency of the model. A nomogram was then constructed.

Results

Of the 175 included patients, 138 were male, of which 85 had moderately severe to severe HTGP. Patients with low skeletal muscle mass (LSMM) and high MCTSI were significantly more likely to have moderately severe to severe HTGP. Patients with LSMM had lower body mass index, lower HDL‐C level, higher amylase level, prevalence of surgery, shorter umbilical waist circumference, and longer length of hospital stay. Univariate and multivariate logistic regression analyses confirmed that female sex, lipase, total cholesterol, LSMM‐MCTSI (P = .004, odds ratio = 23.105), and albumin were risk factors. The TOTAL model that combined LSMM‐MCTSI and clinical risk parameters performed best (AUCs = 0.875), followed by other models (LSMM‐MCTSI: AUCs = 0.762, MCTSI: AUCs = 0.728). The Delong test revealed significant difference. Finally, a nomogram was developed to predict the severity of HTGP.

Conclusion

The performance of MCTSI in predicting severity can be improved by considering LSMM, which is a promising strategy for the treatment of HTGP.
Extreme rainless periods in Pannonian Basin
Authors: Srdjevic Bojan , Srdjevic Zorica , Benka Pavel
Published: June 2022

This paper analyses extreme meteorological droughts in the territory of the Pannonian Basin in central and southeastern Europe. Droughts are treated from an agricultural perspective as periods of consecutive days with very little or no rainfall at all. By using data from the historical period 1981–2010, time intervals longer than 20 days with less than 3 mm per day during the growing season April–September are examined to determine theoretical and empirical distributions of their number and durations. Related discrete stochastic process of extremes is analysed by the Zelenhasic–Todorovic (ZT) method, successfully applied in hydrology and meteorology (e.g., peak flows, low flows, meteorological droughts, etc.). The method is applied to 52 locations across Pannonia Basin. At each location, the Poisson distribution is determined for the number of droughts, exponential distribution for the duration of droughts, and double exponential distribution for the duration of the (annually) longest droughts. To validate the quality of modelling and the results obtained, standard statistical goodness of fit tests are used. Historical data from the period 1981–2010 indicate that the central and northern part of Hungary and the entire territory of Vojvodina Province in the north of Serbia experienced the longest droughts, on average 55–60 days. In statistical terms, across Pannonia Basin once in 100 years drought may occur with an average duration of 56 days. Theoretically longest 100‐year droughts could be expected in the northern part of Hungary (up to 70 days), the eastern part of Romania (up to 68 days), and Serbia (up to 69 days). The 2‐year droughts are on the average duration of 3 weeks. Generated maps of the longest droughts in the basin may help to reduce agricultural risks due to global warming and other negative impacts of climate change.
The emergence of prolonged deadly humid heatwaves
Authors: Wang Xiang‐Sheng , He Lei , Ma Xiao‐Hu , Bie Qiang , Luo Lin , Xiong You‐Cai , Ye Jian‐Sheng
Published: June 2022

Deadly humid heat conditions exceeding human thermoregulatory capacity have been reported; however, whether and where the deadly humid heat events occur consecutively across the land surface are largely unknown. We calculate the maximum consecutive days of deadly humid heat, defined as daily maximum wet‐bulb temperature (TWmax) ≥35°C, for observations of 9,278 meteorological stations and for simulations of 14 global climate models. We further define short and long deadly humid heatwaves as a period of 3–4 and ≥5 consecutive days with daily TWmax ≥35°C, respectively. Our analyses show that six stations in some subtropical regions have experienced deadly humid heat with daily TWmax ≥35°C, but only occurs in individual days. Deadly humid heatwaves increase exponentially as the global mean temperature rising. When limiting global warming within 1.5°C, long deadly humid heatwaves will not occur across the land surface, and short deadly humid heatwaves will only emerge in some drylands but not in humid areas. Under 2°C warming, 0.09% of the global land, 0.42% of the human population, and 0.56% of the global centres of crop diversity are projected to be exposed to long deadly humid heatwaves. Meanwhile, 18% of the deadly humid heatwaves lasting ≥3 consecutive days will occur in humid areas; the fractions are projected to rapidly increase in humid areas as temperature rising further. At the end of the century, the percentage of land areas and human population exposed to deadly humid heatwaves lasting ≥3 consecutive days are expected to be 76‐times higher than that under 1.5°C warming level. Our finding suggests that keeping global warming within 1.5°C will significantly constrain the emergence of prolonged deadly humid heatwaves and thus reduce the risk of the human population especially outdoor agricultural workers.
Dynamic Creativity: A Person × Task × Situation Interaction Framework
Authors: Tromp Catrinel , Sternberg Robert J.
Published: June 2022

Existing theories and frameworks generally have regarded creativity as inhering in a person, a task, a situation, or a combination of 2 of these 3 elements. After reviewing these approaches, and frameworks that are based on the interaction of more than 2 components, we propose a Person × Task × Situation synergistic paradigm, according to which creativity is dynamic and can be fully understood only as an interaction of all 3 of the elements. Building on the strengths of existing frameworks, our P × T × S proposal highlights: (a) the need to include the other 2 elements as moderators, regardless of which element is the central or starting point of the analysis, (b) the idea that the extent to which each element influences the others and the degree of overlap among elements can vary, and (c) the dynamic aspect of creativity, associated with changes in different persons across the lifespan, for different creative tasks, and for different situations. In addition to contributing an integrative theoretical account, this framework has significant, pragmatic implications for both the assessment and the development of creativity. We end with a call for both researchers and practitioners who test for or teach for creativity to specify the range of persons, tasks, and situations to which their assessments or training generalize.
Nutrient profile and effect of processing methods on the composition and functional properties of lentils (Lens culinaris Medik): A review
Authors: Dhull Sanju Bala , Kinabo Joyce , Uebersax Mark A.
Published: June 2022

Grain legumes or pulses, including lentil (Lens culinaris Medik), have gained increasing popularity among consumers and food processors in recent years. This trend has been driven by the consumers opting for plant‐based proteins and environmentally sustainable food sources. Global production of lentils has more than doubled since 2001 (from 3.15 to 6.58 million metric tons in 2020), which signifies the commercial importance of this nutrient‐dense legume. As per the USDA's nutrients data (2022), lentil contains 24.6% protein, 63.4% carbohydrates, 2.7% ash content, and 1.1% total fat. High amount of dietary fiber, slowly digestible starch and potassium, and low sodium in lentil align well with consumer choices for healthy foods. Many studies have reported on the health benefits of consuming lentils, especially being effective in reducing various health conditions, such as hypertension, cardiovascular diseases, diabetes mellitus, and cancer. The relatively higher protein and lower carbohydrates content of lentil compared with cereal grains can help in expanding the utilization of lentils and lentil‐based ingredients to develop new products. Combined with high dietary fiber, resistant starch, and bioactive polyphenolic content, the demonstrated nutritional benefits can fill the ever‐increasing demand for plant‐based proteins well beyond traditional consumption of lentils in developing countries. This article reviews the composition and nutrient profile of raw and processed lentils, effect of various processing methods on composition and nutrient profile, and health benefits of lentils.
Parental exposure of Eastern oysters (Crassostrea virginica) to elevated pCO2 mitigates its negative effects on early larval shell growth and morphology
Authors: McNally Elise M. , Downey‐Wall Alan M. , Titmuss F. Dylan , Cortina Camila , Lotterhos Kathleen , Ries Justin B.
Published: June 2022

Larvae of marine calcifying organisms are particularly vulnerable to the adverse effects of elevated pCO2 on shell formation because of their rapid calcification rates, reduced capacity to isolate calcifying fluid from seawater, and use of more soluble polymorphs of calcium carbonate. However, parental exposure to elevated pCO2 could benefit larval shell formation through transgenerational plastic responses. We examined the capacity of intergenerational exposure to mitigate the adverse effects of elevated pCO2 on Eastern oyster (Crassostrea virginica) early larval shell growth, shell morphology, and survival. Adult oysters were exposed to control (572 ppm pCO2) or elevated pCO2 (2827 ppm pCO2) conditions for 30 d during reproductive conditioning. Offspring from each parental treatment were produced using a partial North Carolina II cross design and grown under control and elevated pCO2 conditions for 3 d. We found evidence of transgenerational plasticity in early larval shell growth and morphology, but not in survival, in response to the parental pCO2 exposure. Larvae from parents exposed to elevated pCO2 exhibited faster shell growth rates than larvae from control parents, with this effect being significantly larger when larvae were grown under elevated pCO2 compared to control conditions. Parental exposure to elevated pCO2, however, was insufficient to completely counteract the adverse effects of the prescribed elevated pCO2 on early larval shell formation and survival. Nevertheless, these results suggest that oysters have some capacity to acclimate intergenerationally to ocean acidification.
Isotopic signatures of biotic and abiotic N2O production and consumption in the water column of meromictic, ferruginous Lake La Cruz (Spain)
Authors: Tischer Jana , Zopfi Jakob , Frey Claudia , Magyar Paul M. , Brand Andreas , Oswald Kirsten , Jegge Corinne , Frame Caitlin H. , Miracle María R. , Sòria‐Perpinyà Xavier , Vicente Eduardo , Lehmann Moritz F.
Published: June 2022

Lakes can be important sources of the potent greenhouse gas nitrous oxide (N2O) to the atmosphere, but to what extent abiotic processes may contribute to lacustrine N2O production remains uncertain. We assessed pathways of N2O production and reduction in the water column of meromictic and iron‐rich Lake La Cruz, Spain, including chemodenitrification‐induced N2O formation via the reaction of reactive nitrogen (N) (e.g., ) with ferrous iron (Fe[II]). In the oxic waters (~8–10 m), N2O concentrations above atmospheric equilibrium were associated with comparatively low δ15N‐N2O, high , and high N2O 15N‐site‐preference (SP) values (up to ~29‰), suggesting N2O production by nitrification. N2O concentrations were highest (23–33 nM) near the depth of oxygen depletion (~11–14.5 m), likely due to production by nitrifier denitrification and/or denitrification, as indicated by decreasing SP values (as low as 12‰). Further below (~14.5–17 m), N2O consumption was indicated by increasing SP values and a δ18O‐vs.‐δ15N relationship (1.8–2.9) typical for stand‐alone N2O reduction. The coupled N‐vs.‐O isotope signatures thus highlight the spatial, redox‐dependent separation of incomplete and complete denitrification. In incubations with sterile‐filtered lake water and 15N‐labeled or unlabeled substrate, was reduced by Fe2+ to N2O, even at low nitrite concentrations (5 μM ). In the water column, the spatial separation of and Fe(II) during our samplings appears to preclude elevated rates of chemodenitrification, but during periods of overlapping and Fe(II) in Lake La Cruz, and potentially in other lakes, its distinct N2O δ18O‐vs.‐δ15N relationship of ~1 : 1, as experimentally determined, could help to detect it.
Antimicrobial Polymers of Linear and Bottlebrush Architecture: Probing the Membrane Interaction and Physicochemical Properties
Authors: Bapolisi Alain Murhimalika , Kielb Patrycja , Bekir Marek , Lehnen Anne‐Catherine , Radon Christin , Laroque Sophie , Wendler Petra , Müller‐Werkmeister Henrike M. , Hartlieb Matthias
Published: June 2022

Polymeric antimicrobial peptide mimics are a promising alternative for the future management of the daunting problems associated with antimicrobial resistance. However, the development of successful antimicrobial polymers (APs) requires careful control of factors such as amphiphilic balance, molecular weight, dispersity, sequence, and architecture. While most of the earlier developed APs focus on random linear copolymers, the development of APs with advanced architectures proves to be more potent. It is recently developed multivalent bottlebrush APs with improved antibacterial and hemocompatibility profiles, outperforming their linear counterparts. Understanding the rationale behind the outstanding biological activity of these newly developed antimicrobials is vital to further improving their performance. This work investigates the physicochemical properties governing the differences in activity between linear and bottlebrush architectures using various spectroscopic and microscopic techniques. Linear copolymers are more solvated, thermo‐responsive, and possess facial amphiphilicity resulting in random aggregations when interacting with liposomes mimicking Escheria coli membranes. The bottlebrush copolymers adopt a more stable secondary conformation in aqueous solution in comparison to linear copolymers, conferring rapid and more specific binding mechanism to membranes. The advantageous physicochemical properties of the bottlebrush topology seem to be a determinant factor in the activity of these promising APs.
“On Chorea”: 150 Years of the Beginning of Hope
Authors: Franklin Gustavo L. , Teive Hélio A.G. , Meira Alex T. , Nepomuceno Adriana M.T. , Tabrizi Sarah J.
Published: June 2022

“On Chorea” by George Huntington was published on April 13, 1872, in The Medical and Surgical Reporter of Philadelphia. Despite being a milestone in the recognition of the disease that later would bear his name, some myths and curiosities continue to surround the history of this publication and its author. In this History, the authors pay tribute to the 150th anniversary of the publication of this iconic article. © 2022 International Parkinson and Movement Disorder Society.
Effect of KRAS mutations and p53 expression on the postoperative prognosis of patients with colorectal cancer
Authors: Wang Lingfeng , Lin Shengtao , Yang Changshun , Cai Shaoxin , Li Weihua
Published: June 2022

Background

In the occurrence and development of colorectal cancer, p53 is an important regulator downstream of the MAPK signaling pathway and plays an important role in inhibiting abnormal proliferation signals generated by KRAS mutations. The purpose of this study is to explore the correlation between KRAS mutations and p53 expression and evaluate their prognosis values in colorectal cancer.

Methods

PCR technology and immunohistochemical (IHC) staining were used to detect KRAS mutation status and p53 expression level in 266 specimens of colorectal adenocarcinoma. Based on p53 expression level, these were divided into high expression and normal groups. Patients with KRAS mutations were divided into mutant and wild‐type groups. The two were combined with each other to analyze the relationship between patients' clinical data and their impact on the prognosis.

Results

KRAS mutations were found in 38.6% of the patients and 40.8% had a high p53 expression. There was no significant difference in the overall survival rate of patients, with or without KRAS gene mutations, and p53 expression level. In the group of patients with KRAS mutations, the survival time of patients with a high p53 expression was significantly lower than that of patients with a normal p53 expression (p = 0.020, log‐rank test). Multivariate analysis showed that p53 high expression is an independent risk factor for the overall survival time of patients with KRAS mutations (HR = 2.330, 95% CI = 1.041–5.216, p < 0.05).

Conclusion

Colorectal cancer patients with KRAS mutations with a high p53 expression have a poor prognosis.
Oblique wave interaction by two thin vertical barriers over an asymmetric trench
Authors: Sarkar Biman , Roy Ranita , De Soumen
Published: June 2022

A breakwater model is developed to analyse the wave propagation over an asymmetric rectangular trench in presence of two thin vertical partially immersed barriers. With the help of eigenfunction expansion, the problem is reduced to four weakly singular integral equations involving horizontal component of velocity across the gaps below the two barriers and above the two corners of the trench. The integral equations are solved by employing Galerkin technique involving expansion in terms of Chebyshev polynomials for the two unknown velocities across the gaps below the barrier multiplied by an weight function having square root singularity at an end and Gegenbauer polynomials for the other two unknown velocities above the two corners of the trench multiplied by an weight function having one‐third singularity at an end. Numerical results for the reflection and transmission coefficients are presented graphically against wavenumber for different configurations of the barriers and trench. The accuracy of the numerical results is validated by comparing the reflection coefficients and the known results associated with barriers and trench available in the literature.
Time‐varying piecewise nonlinear dynamic model of the vibrating machinery with elliptical trajectory consider the interactions between its frame and particles
Authors: Li Lingxuan , Zhang Haonan , Zhong Hao
Published: June 2022

Vibrating machinery with an elliptical trajectory widely exists. The bulk particles show a regular sliding motion and throwing motion under the periodic vibration of the frame. It is essential for the theoretical design and engineering application of such machinery to study the particle's motion theory based on considering the interactions between particles and frame in detail. In the first, a time‐varying piecewise nonlinear dynamic model of the system is established based on the force analysis of the particles in the state of sliding and throwing motion. The dimensionless equations of systems with nonlinear terms are deduced. After that, the feasibility of using a single particle to study the particle flow's movement is verified by the discrete element method. Then, the system's approximate steady‐state analytical solution is obtained by the incremental harmonic balance method. Its numerical solutions are solved by the Newmark‐β method, and the solutions obtained by the three methods are verified mutually. In addition, the Sommerfeld effect in vibration system and the system's related parameters are analyzed. Finally, an experimental platform of particles' movement is built. The feasibility of the theoretical analysis in this article was verified by particle's movement experiments.
Molecular deciphering of primary liver neuroendocrine neoplasms confirms their distinct existence with foregut‐like profile
Authors: de Mestier Louis , Nicolle Rémy , Poté Nicolas , Rebours Vinciane , Cauchy François , Hentic Olivia , Maire Frédérique , Ronot Maxime , Lebtahi Rachida , Sauvanet Alain , Paradis Valérie , Ruszniewski Philippe , Couvelard Anne , Cros Jérôme
Published: June 2022

Isolated hepatic localizations of neuroendocrine tumors (NETs) are generally considered as metastatic NETs of unknown primary but could correspond to primary hepatic NETs (PHNETs), a poorly explored entity. We aimed to describe the clinicopathological and molecular features of PHNETs and compare them with other primary NETs. We assembled a retrospective cohort of patients managed for hepatic localization of NET without extra‐hepatic primary tumor after exhaustive clinical, imaging, and immunohistochemical characterization. We performed whole‐exome sequencing with mutational and copy number analysis. Transcriptomic profiles were compared with pancreatic (n = 31), small‐bowel (n = 22), and lung (n = 15) NETs using principal component analysis, unsupervised clustering, and gene set enrichment analysis. Among 27 screened patients, 16 had PHNET (solitary tumor in 63%, median size 11 cm, G2 NETs in 81%) following clinical and pathological review. DNA analyses showed ‘foregut‐like’ genomic profiles with frequent alterations in pathways of Fanconi DNA repair (75%), histone modifiers (58%), adherens junctions (58%), and cell cycle control (50%). The most frequently involved genes were KMT2A (58%), ATM (42%), CDH1, CDKN2C, FANCF, and MEN1 (33% each). Transcriptomic analyses showed that PHNETs clustered closer to foregut (pancreatic, lung) NETs than to midgut (small‐bowel) NETs, while remaining a distinct entity with a specific profile. Assessment of potentially predictive biomarkers suggested efficacy of treatments usually active in foregut NETs. In conclusion, PHNETs display a foregut‐like molecular profile distinct from other types of NETs, with recurrent molecular alterations. Upon exhaustive work‐up to exclude an unrecognized primary tumor, PHNETs should not be considered metastatic NETs from an unknown primary. © 2022 The Pathological Society of Great Britain and Ireland.
Peak density of immature nerve cells occurs with high‐grade dysplasia in intraductal papillary mucinous neoplasms of the pancreas
Authors: Trinh Vincent Quoc‐Huy , Roland Joseph Thomas , Wong Jahg , Revetta Frank , Patel Krutika , Shi Chanjuan , DelGiorno Kathleen E , Carter Bruce D , Tan Marcus Chuan Beng
Published: June 2022

The development of neural structures within tumors is now considered vital for carcinogenesis. However, the time course of this development in human pre‐invasive neoplasia has been incompletely described. Therefore, we performed a detailed analysis of nerves across the neoplastic spectrum in resected intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Histology and multiplexed immunochemistry demonstrated that nerve density increased from low‐grade (LG) to high‐grade dysplasia (HG) but did not further increase once invasive IPMN (INV IPMN) was present. Higher nerve density correlated with increasing expression of nerve growth factor (NGF) by the tumor cells. Intra‐tumoral nerves were immature and lacked markers of sympathetic, parasympathetic, and sensory lineages. Here, we show for the first time the presence of neural precursor cells (NPCs) within the stroma of pancreatic tumors. The density of these doublecortin (DCX)‐positive NPCs increased from LG to HG, but not from HG to INV IPMN. We conclude that peak neural density of tumors is reached in high‐grade dysplasia (often termed carcinoma in situ) rather than after invasion. These findings suggest that nerve–tumor interactions are important in IPMN progression and may serve as the basis for future mechanistic studies and novel therapeutic modalities. © 2022 The Pathological Society of Great Britain and Ireland.
End‐of‐life care quality for children with cancer who receive palliative care
Authors: Ananth Prasanna , Lindsay Meghan , Nye Russell , Mun Sophia , Feudtner Chris , Wolfe Joanne
Published: June 2022

Background: We previously developed stakeholder‐informed quality measures to assess end‐of‐life care quality for children with cancer. We sought to implement a subset of these quality measures in the multi‐center pediatric palliative care (PPC) database.

Procedures: We utilized the Shared Data and Research database to evaluate the proportion of childhood cancer decedents from 2017–2021 who, in the last 30 days of life, avoided chemotherapy, mechanical ventilation, intensive care unit admissions, and > 1 hospital admission; were enrolled in hospice services, and reported ≤ 2 highly distressing symptoms. We then explored patient factors associated with the attainment of quality benchmarks.

Results: Across 79 decedents, 82% met ≥ 4 quality benchmarks. Most (76%) reported > 2 highly distressing symptoms; 17% were enrolled in hospice. In univariable analyses, patients with an annual household income ≤$50,000 had lower odds of hospice enrollment and avoidance of mechanical ventilation or intensive care unit admissions near end of life (odds ratio [OR] 0.10 [95% confidence interval (C.I.) 0.01, 0.86], p = 0.04; OR 0.13 [0.02, 0.64], p = 0.01; OR 0.36 [0.13, 0.98], p = 0.04, respectively). In multivariable analyses, patients with an income ≤$50,000 remained less likely to enroll in hospice, after adjusting for cancer type (OR 0.10 [0.01, 0.87]; p = 0.04).

Conclusions: Childhood cancer decedents who received PPC met a large proportion of quality measures near the end of their life. Yet, many reported highly distressing symptoms. Moreover, patients with lower household incomes appeared less likely to enroll in hospice and more likely to receive intensive hospital services near the end of life. This study identifies opportunities for palliative oncology quality improvement.
Adherence to dietary prescriptions in patients with acute food protein‐induced enterocolitis syndrome
Authors: Miceli Sopo Stefano , Sinatti Dario , Sodero Giorgio , Gelsomino Mariannita , Mastellone Francesco
Published: June 2022

Food protein‐induced enterocolitis syndrome (FPIES) is a non‐Immunoglobulin (non‐IgE)‐mediated food allergy. The elimination diet is the only therapy, the culprit food will be reintroduced if tolerance is acquired. However, it is possible that patients do not follow the recommendations given by the healthcare professional. We investigated if our advice to avoid the trigger food in patients with active FPIES and to reintroduce it in the diet in patients who achieved tolerance had been implemented. We interviewed by telephone the parents of children who were diagnosed with acute FPIES. About 23.2% of our patients disregarded our dietary recommendations: 6/42 (14.3%) of patients who passed a tolerance oral food challenge (OFC) did not eat the trigger food, 4/22 (18.2%) of patients who failed OFC ate the trigger food, and 9/18 (50.0%) of patients who did not perform a tolerance OFC ate the trigger food. We have analyzed some possible influencing factors and no difference was found to be statistically significant. Our results are in line with those reported for IgE‐mediated food allergies. As has already been proposed by others, we suggest reassessing food consumption in all patients after a food challenge.
Calibration and validation of the rabbit model of electrolytic‐mediated arterial thrombosis against the standard‐of‐care anticoagulant apixaban
Authors: Wong Pancras C. , Crain Earl
Published: June 2022

Apixaban is a factor Xa (FXa) inhibitor and standard‐of‐care anticoagulant with FXa Ki and plasma protein binding (free fraction) averages 0.08 nM and 0.13 in humans and 0.16 nM and 0.37 in rabbits, respectively. Apixaban at the approved dose of 5 mg BID achieved maximum and minimum plasma concentration of 373 nM (95% CI: 198 – 699 nM) and 224 nM (95% CI 89–501 nM), respectively, in patients with nonvalvular atrial fibrillation (AF). We calibrated the rabbit model of electrolytic‐mediated arterial thrombosis (ECAT) against apixaban and correlated the potencies derived from the rabbit ECAT to in vivo efficacious exposure levels in AF patients. Vehicle and apixaban at multiple doses were infused IV in ECAT rabbits and their effects on thrombus weight were measured. Apixaban exhibited dose‐related efficacy in preventing thrombosis in ECAT rabbits with EC20, EC50, EC60, EC70 and EC80 of 18, 101, 169, 296, and 585 nM, respectively. After correcting for the human‐to‐rabbit potency based on FXa Ki and plasma protein binding, we estimated a rabbit‐equally‐effective plasma concentration of 157 and 259 nM to the trough and peak plasma concentration in AF patients treated with 5 mg BID of apixaban. These rabbit‐equally‐effective plasma concentrations matched well with the rabbit ECAT EC60 and EC70. This study supports the potential of the rabbit ECAT to predict in vivo therapeutic drug exposure of FXa inhibitors. Achieving human‐equally‐effective plasma concentrations to the rabbit ECAT EC60 and EC70 may produce clinical efficacy in patient populations like AF.
Oridonin relieves depressive‐like behaviors by inhibiting neuroinflammation and autophagy impairment in rats subjected to chronic unpredictable mild stress
Authors: Liang Liang , Wang Hui , Hu Ying , Bian Hetao , Xiao Ling , Wang Gaohua
Published: June 2022

Major depressive disorder (MDD) is a severe life‐threatening disorder with increasing prevalence. However, the mechanistic interplay between depression, neuroinflammation, and autophagy is yet to be demonstrated. This study investigated the effect of Oridonin on CUMS‐induced depression, neuroinflammation, and autophagy impairment. Male 4‐week‐old Sprague–Dawley rats were subjected to chronic unpredictable mild stress (CUMS), some of which were injected with Oridonin, fluoxetine (FLX), or their combination at different durations of CUMS. CUMS significantly increased the levels of cytokines (IL‐1β, IL‐18, and caspase‐1), reduced autophagy‐related protein levels (Beclin‐1, p62, Atg5, and LC3B), and caused microglia cells activation. Oridonin prevented and reversed the depressive‐like behavior. Furthermore, it has a stronger and longer‐lasting antidepressant effect than FLX. And the antidepressant effect of Oridonin in combination with fluoxetine was greater than that of high‐dose fluoxetine alone. In addition, Oridonin significantly normalized autophagy‐related protein levels, and reduced levels of cytokines by blocking the interaction between NLRP3 and NEK7. Similarly, Oridonin abolished levels of cytokines and reversed autophagy impairment in LPS‐activated BV2 cells. All these results supported our hypothesis that Oridonin possesses potent anti‐depressive action, which might be mediated via inhibition of neuroinflammation and autophagy impairment by blocking the interaction between NLRP3 and NEK7.
Isobavachalcone: A comprehensive review of its plant sources, pharmacokinetics, toxicity, pharmacological activities and related molecular mechanisms
Authors: Xing Nan , Meng Xianli , Wang Shaohui
Published: June 2022

Isobavachalcone (IBC), also known as isobapsoralcone, is a natural flavonoid widely derived from many medicinal plants, including Fabaceae, Moraceae, and so forth. IBC has been paid more and more attention by researchers in recent years due to its pharmacological activity in many diseases. This review aims to describe in detail the plant sources, pharmacokinetics, toxicity, pharmacological activities, and molecular mechanisms of IBC on various diseases. We found that IBC can be obtained not only by extraction but also by chemical synthesis. Pharmacokinetic studies have shown that IBC has low bioavailability, but can penetrate the blood–brain barrier and is widely distributed in the brain. Its pharmacological activities mainly include anticancer, antibacterial, anti‐inflammatory, antiviral, neuroprotective, bone protection, and other activities. In particular, IBC shows strong anti‐tumor and anti‐inflammatory therapeutic potential due to its anti‐cancer and anti‐inflammatory activities. However, due to its hepatotoxicity, there may be more drug interactions. Therefore, more and more in‐depth studies are needed for its clinical application. Mechanically, IBC can induce the production of reactive oxygen species (ROS), inhibit AKT, ERK, and Wnt pathways, and promote apoptosis of cancer cells through mitochondrial or endoplasmic reticulum pathways. IBC can inhibit the NF‐κB pathway and the production of multiple inflammatory mediators by activating NRF2/HO‐1 pathway, thus producing anti‐inflammatory effects. Moreover, we discussed the limitations of current research on IBC and put forward some new perspectives and challenges, which provide a strong basis for clinical application and new drug development of IBC in the future.
Controllable fast light in quantum dot molecules assisted hybrid optomechanical system
Authors: Ghaffar Ammal Abdul , Khan Muhammad Aslam , Niaz Shanawer , Khan Farooq , Jamil Muhammad Ashfaq , Ramay Shahid M.
Published: June 2022

We investigate the superluminal effect of transmitted probe field in three‐level quantum dot molecules (QDMs) assisted optomechanical system which consist of mechanical resonator. We show that the superluminal behavior of transmitted probe field can be controlled by changing the tunneling strength and number of QDMs inside the cavity. Furthermore, it is shown that in the absence of tunneling strength, the transmitted probe field shows the fast light effect and by increasing the number of QDMs, the enhancement in superluminal behavior is decreased and converts into slow light. While, in the presence of the tunneling strength, with the increase of the number of QDMs the superluminal behavior of transmitted field is obtained at smaller detuning frequency. The influence of tunneling strength and number of QDMs on superluminal part of the transmitted probe field is quite useful in optical memory, optical buffers, and quantum information processing.
Respiratory viral co‐infections in patients with COVID‐19 and associated outcomes: A systematic review and meta‐analysis
Authors: Krumbein Hanna , Kümmel Lara S. , Fragkou Paraskevi C. , Thölken Clemens , Hünerbein Ben L. , Reiter Rieke , Papathanasiou Konstantinos A. , Renz Harald , Skevaki Chrysanthi
Published: June 2022

The aim of this systematic review and meta‐analysis was to critically assess the published literature related to community‐acquired viral co‐infections and COVID‐19 and to evaluate the prevalence, most identified co‐pathogens, and relevant risk factors. Furthermore, we aimed to examine the clinical features and outcomes of co‐infected compared to mono‐infected COVID‐19 patients. We systematically searched PubMed, Web of Science, Embase, Scopus, and The Cochrane Library for studies published from 1 November 2019 to 13 August 2021. We included patients of all ages and any COVID‐19 severity who were screened for respiratory viral co‐infection within 48 h of COVID‐19 diagnosis. The main outcome was the proportion of patients with a respiratory viral co‐infection. The systematic review was registered to PROSPERO (CRD42021272235). Out of 6053 initially retrieved studies, 59 studies with a total of 16,643 SARS‐CoV‐2 positive patients were included. The global pooled prevalence was 5.01% (95% CI 3.34%–7.27%; I2 = 95%) based on a random‐effects model, with Influenza Viruses (1.54%) and Enteroviruses (1.32%) being the most prevalent pathogens. Subgroup analyses showed that co‐infection was significantly higher in paediatric (9.39%) than adult (3.51%) patients (p‐value = 0.02). Furthermore, co‐infected patients were more likely to be dyspnoeic and the odds of fatality (OR = 1.66) were increased. Although a relatively low proportion of COVID‐19 patients have a respiratory viral co‐infection, our findings show that multiplex viral panel testing may be advisable in patients with compatible symptoms. Indeed, respiratory virus co‐infections may be associated with adverse clinical outcomes and therefore have therapeutic and prognostic implications.
Lotus Seed Starch: A Novel Functional Ingredient with Promising Properties and Applications in Food—A Review
Authors: Dhull Sanju Bala , Chandak Ankita , Collins Maurice N. , Bangar Sneh Punia , Chawla Prince , Singh Ajay
Published: June 2022

Lotus (Nelumbo nucifera G.) seeds are rich in nutrients and mainly used for food and medicinal applications. The seeds are an important food item in many countries and are generally considered a low glycemic index food. Starch is a major component of lotus seeds and may amount to over 50% of the dry weight. The quality of lotus seed products is mainly determined their starch properties, such as gelatinization and retrogradation. This review comprehensively summarizes recent developments in isolation, modifications, and applications of lotus seed starch (LS). This survey highlights different properties of native and modified LS in comparison with other starches. Native LS has been found with high amylose content (20–35%), high peak gelatinization temperatures (>70 °C), and pasting temperatures (>75 °C). The high amylose content has contributed to lower swelling power and fast retrogradation of LS. The modification of LS has been done using different methods, including thermal, microwave, high pressure, chemical, and enzymatic processing for functionality improvement. Native and modified LS have promising potential to be a valuable functional ingredient in different food and other applications. Finally, an outlook on the future possibilities for utilization of LS is provided.
Energy metabolism in mammalian sperm motility
Authors: Amaral Alexandra
Published: June 2022

Mammalian sperm, the only cells that achieve their purpose outside their organism of origin, have to swim vigorously within the female reproductive tract to reach an oocyte. Flagellar dyneins drive sperm motility, which accounts for the consumption of high amounts of ATP. The two main ATP‐producing metabolic pathways are compartmentalized in sperm: oxidative phosphorylation in the midpiece and glycolysis in the principal piece. The relative preponderance of these pathways has been discussed for decades (the so‐called sperm energy debate). The debate has been muddled by species‐specific variances and by technical constraints. But recent findings suggest that sperm from most mammalian species employ a versatile metabolic strategy to maintain motility according to the physiological environment. Different metabolic pathways likely coordinate by using exogenous and/or endogenous substrates in order to produce ATP efficiently. Defects in any of these pathways (glycolysis, mitochondrial oxidative phosphorylation, Krebs cycle, fatty acids oxidation, and ketone bodies oxidation, among others) may disturb sperm motility and be at the origin of male infertility. Understanding sperm bioenergetics is thus crucial for building new diagnostic tools, and for the development of treatments for patients presenting with low sperm motility. Some of these patients may benefit from personalized metabolic supplementations and dietary interventions.

This article is categorized under:

Reproductive System Diseases > Molecular and Cellular Physiology
Electromagnetic signals of inelastic dark matter scattering
Authors: Baryakhtar Masha , Berlin Asher , Liu Hongwan , Weiner Neal
Published: June 2022

Abstract

Light dark sectors in thermal contact with the Standard Model can naturally produce the observed relic dark matter abundance and are the targets of a broad experimental search program. A key light dark sector model is the pseudo-Dirac fermion with a dark photon mediator. The dynamics of the fermionic excited states are often neglected. We consider scenarios in which a nontrivial abundance of excited states is produced and their subsequent de-excitation yields interesting electromagnetic signals in direct detection experiments. We study three mechanisms of populating the excited state: a primordial excited fraction, a component up-scattered in the Sun, and a component up-scattered in the Earth. We find that the fractional abundance of primordial excited states is generically depleted to exponentially small fractions in the early universe. Nonetheless, this abundance can produce observable signals in current dark matter searches. MeV-scale dark matter with thermal cross sections and higher can be probed by down-scattering following excitation in the Sun. Up-scatters of GeV-scale dark matter in the Earth can give rise to signals in current and upcoming terrestrial experiments and X-ray observations. We comment on the possible relevance of these scenarios to the recent excess in XENON1T.
50 Years of translation structures
Authors: Lunardon Guglielmo
Published: June 2022

In this paper the term translation structure will denote any geometric object canonically constructed from an elementary abelian group. Hence, translation weak affine spaces, translation planes, linear sets, translation ovoids of polar spaces, translation generalized quadrangles and linear MRD-codes are examples of translation structures. I will present my personal excursus in the theory of finite translation structures, from the pioneering times of B. Segre, A. Barlotti and G. Tallini to these days. My aim is not to give a complete survey of the known results but to describe the influence of translation structures in proofs or disproofs of some conjectures in different areas of Finite Geometries and how valuable tool they were giving significant contributions in different areas of Discrete Mathematics.
Einfluss der Arbeitsbedingungen und des Gehalts auf die Leiharbeit für Intermediate-Care- und Intensivstationen
Authors: Hermes C. , Blanck-Köster K. , Gaidys U. , Rost E. , Petersen-Ewert C.
Published: June 2022

Hintergrund

Leiharbeit in der Pflege wird als Arbeitsform verwendet, um offenen Personalstellen in Kliniken zu begegnen. Sowohl Krankenhausträger als auch Pflegekräfte sehen dies aus unterschiedlichen Gründen kritisch.

Ziel

Zweck dieser Untersuchung war es herauszufinden, welches persönliche Nettoeinkommen Pflegekräfte von deutschen Intensivstationen und Intermediate-Care-Stationen als „gerecht und ausreichend“ für ihre Tätigkeit empfinden und welchen Einfluss das Gehalt auf die Wechselwilligkeit in die Leih‑/Zeitarbeit bzw. wieder zurück in eine Festanstellung haben.

Methode

Von September bis Oktober 2020 wurde eine anonymisierte Onlineumfrage unter Pflegenden von Intermediate-Care-Stationen, Intensivstationen und Funktionsbereichen im deutschsprachigen Raum durchgeführt. Die Auswertung erfolgte mittels deskriptiver Statistik.

Ergebnis

Von 1203 Teilnehmer_innen (TN) konnten 1036 (86 %) in Deutschland Arbeitende ausgewertet werden. Die Frage nach dem persönlichen Nettoeinkommen wurde von 1032 (99 %) TN beantwortet. Der überwiegende Anteil der Befragten (n = 522) gibt an, über ein persönliches Nettoeinkommen von 2000–2999 €/Monat zu verfügen. Der Wunsch, in die Leiharbeit zu gehen, ist in der untersuchten Stichprobe geringer, je höher das persönliche Nettoeinkommen ist. Die TN in Festanstellung ohne Nebenerwerb empfinden ein persönliches Nettoeinkommen von 3200 €/Monat (Median 3200 €; IQR 2800–3800 €) als ausreichend und gerecht für ihre Tätigkeit. Von den Leiharbeiter_innen gaben 142 Personen an, dass ein persönliches Nettoeinkommen von 3200 €/Monat (Median 3200 €; Interquartilsabstand 3000–3950 €) ausreichend wäre, um von der Leiharbeit zurück in eine Festanstellung zu wechseln.

Schlussfolgerung

Die Intensivpflegenden dieser Umfrage empfinden ein Gehalt von 3200 €/Monat netto als ausreichend und gerecht für ihre Tätigkeit. Die Gehaltshöhe kann ein Parameter für die Entscheidung sein, in die Leiharbeit zu gehen, aber auch um wieder in die Festanstellung zu wechseln. Unabhängig vom Gehalt wurden bessere Arbeitsbedingungen für alle befragten Gruppen als essenzieller Bestandteil in Bezug auf die Arbeitszufriedenheit angegeben.
Anterior ankle impingment syndrome is less frequent, but associated with a longer absence and higher re-injury rate compared to posterior syndrome: a prospective cohort study of 6754 male professional soccer players
Authors: D’Hooghe Pieter , Waldén Markus , Hägglund Martin , Bengtsson Håkan , Ekstrand Jan
Published: June 2022

Purpose

To study the epidemiology and return to play characteristics of anterior and posterior ankle impingement syndromes (AAIS and PAIS) over 18 consecutive seasons in male professional soccer players.

Methods

Between the 2001–2002 and 2018–2019 seasons, 120 European soccer teams were followed prospectively for various seasons. Time loss injuries and player exposures were recorded individually in 6754 unique players. Injury incidence and burden were reported as the number of injuries and days absence per 1000 h with 95% confidence intervals (CIs). Injury severity was reported as median absence in days with the interquartile range (IQR).

Results

Out of 25,462 reported injuries, 93 (0.4%) were diagnosed as AAIS (38%) or PAIS (62%) in 77 players. AAIS and PAIS were similar regarding injury characteristics except for a greater proportion of AAIS having a gradual onset (69% vs.47%; P = 0.03) and being re-injuries (31% vs. 9%; P = 0.01). Impingement syndromes resulted in an overall incidence of 0.03 injuries (95% CI 0.02–0.03) per 1000 h and an injury burden of 0.4 absence days per 1000 h. PAIS incidence was significantly higher than that for AAIS [0.02 (95% CI 0.002–0.03) vs. 0.01 (95% CI 0.005–0.01) injuries per 1000 h (RR = 1.7). The absence was significantly longer in AAIS than in PAIS [10 (22) vs. 6 (11) days; P = 0.023]. Impingement syndromes that presented with a gradual onset had longer absences in comparison to impingement with an acute onset [8 (22) vs. 5 (11) days; P = 0.014]. Match play was associated with a higher incidence and greater injury burden than training: 0.08 vs. 0.02 injuries per 1000 h (RR 4.7), respectively, and 0.9 vs. 0.3 days absence per 1000 h (RR 2.5).

Conclusion

Ankle injuries are frequent in men’s professional soccer and ankle impingement is increasingly recognized as a common source of pain, limited range of motion, and potential time loss. In our study, ankle impingement was the cause of time loss in less than 0.5% of all injuries. PAIS was more frequently reported than AAIS, but AAIS was associated with more absence days and a higher re-injury rate than PAIS. The findings in this study can assist the physician in best practice management on ankle impingment syndromes in professional football.

Level of evidence

II.