bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of subjects who are lean, overweight or obese with nonalcoholic fatty liver disease: A cohort study in China
Authors: Lan Yanqi , Lu Ying , Li Jinfeng , Hu Shiqi , Chen Shuohua , Wang Yanhong , Yuan Xiaojie , Liu Hongmin , Wang Xiaomo , Wu Shouling , Wang Li
Published: October 2022

The ability to determine the prognosis of lean nonalcoholic fatty liver disease (NAFLD) is essential for decision making in clinical settings. Using a large community‐based Chinese cohort, we aimed to investigate NAFLD outcomes by body mass index (BMI). We used the restricted cubic splines method to investigate the dose–response relationship between BMI and outcomes in subjects with NAFLD and those without NAFLD. We included 73,907 subjects from the Kailuan cohort and grouped all subjects into four phenotypes by using NAFLD and BMI (<23 kg/m2). The probability of developing outcomes for individuals with lean NAFLD (LN), overweight/obese NAFLD (ON), overweight/obese non‐NAFLD (ONN), and lean non‐NAFLD (LNN) was estimated. We found a U‐shaped association between BMI and death but a linear positive association concerning cardiovascular disease (CVD) after adjusting for age and other covariates. Compared with the LNN group, the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of the LN, ON, and ONN groups were 1.30 (1.14–1.49), 0.86 (0.80–0.91), 0.84 (0.80–0.89) for all‐cause death, 2.61 (1.13–6.03), 0.74 (0.44–1.26), 1.10 (0.70–1.74) for liver‐related death, 2.12 (1.46–3.08), 1.23 (0.99–1.54), 1.19 (0.98–1.43) for digestive system cancers, and 2.04 (1.40–2.96), 1.30 (1.05–1.61), 1.21 (1.01–1.46) for obesity‐related cancers. Subjects with LN had a significantly higher risk of colorectal cancer and esophagus cancer. However, the ON group had the highest CVD risk (HR, 1.39; 95% CI, 1.27–1.52). The LN group with hypertension had a higher risk of adverse outcomes, and those without hypertension had a similar risk compared to LNN. Conclusion: Subjects with LN may experience a higher risk of all‐cause death, digestive system cancers, and obesity‐related cancers than the other three groups but a lower risk of CVD than ON subjects. LN with hypertension may be a high‐risk phenotype.
Quantifying and comparing the effects of human and organizational factors in electric maloperation accidents with HFACS–CatBoost and SHAP
Authors: Lin Chuan , Xu Qifeng , Huang Yifan
Published: October 2022

The proportion of electric maloperation accidents (EMAs) in substations caused by human and organizational factors (HOFs) has gradually increased. Although there has been some research into the factors affecting EMAs in substations, the available results are insufficient to support the interpretation of HOFs in EMAs. This article explores the relationships between the HOFs and EMAs using Human Factors Analysis and Classification System‐gradient boosting with categorical features support (HFACS–CatBoost) and Shapley Additive exPlanation (SHAP) methods. First, the HFACS framework was introduced to identify 135 EMAs in the Southern Power Grid risk causation. CatBoost was used to construct an accident classification model to analyze the important relationship between accidents and HOFs and to compare and analyze with the extreme gradient boosting (XGBoost) and the binary logistic regression (BLR) to verify the superiority of CatBoost. Finally, to solve the problem of inadequate interpretation of the CatBoost black‐box model, the SHAP value plot was applied to express the contribution degree relationship between accidents and HOFs. The results show that the above method can explore and explain the importance and contribution of HOFs in EMAs. And from this, it is concluded that poor psychological state, poor communication and coordination, inadequate supervision, and inadequate training and education are highly correlated with the occurrence of EMAs. The findings will help substation operations and maintenance staff to develop safety measures to address the confusion of HOFs in substations and prevent the occurrence of EMAs.
Prehospital medicine learning experience for pharmacy residents
Authors: Acquisto Nicole M. , Cushman Jeremy T. , Johnston Melinda , Sensenbach Benjamin
Published: October 2022

Pharmacist collaboration with medical directors and practitioners operating in the emergency medical services (EMS) system can improve overall care, optimize the medication formulary, and decrease medication‐related risk. However, to achieve this, pharmacists must have a fundamental understanding of the prehospital medicine environment. We describe a comprehensive prehospital medicine postgraduate training experience for postgraduate year two (PGY2) emergency medicine (EM) pharmacy residents. A detailed description of the prehospital medicine learning experience (LE) is provided that includes an immersive schedule with diverse EMS exposure, attendance at dedicated EMS‐specific medical resident conferences, didactic and self‐learning requirements, and a scholarly EMS project. Information regarding how this LE is organized and evaluated, as well as challenges and future directions are provided. Program success is highlighted with the reporting of 20 scholarly projects completed by PGY2 EM pharmacy residents from 2006 through 2022 in collaboration with EMS and the Division of Prehospital Medicine. A collaborative and immersive prehospital medicine LE for PGY2 EM pharmacy residents can be mutually beneficial for the training of the pharmacy resident, scholarly productivity supporting regional and statewide change, and EMS personnel.
Pharmacist involvement in sepsis response and time to antibiotics: A systematic review
Authors: Atkins Payton E. , Thompson Bastin Melissa L. , Morgan Rebecca J. , Laine Melanie E. , Flannery Alexander H.
Published: October 2022

Introduction

Sepsis is a life‐threatening medical emergency and a leading cause of morbidity and mortality worldwide. Reductions in time to antibiotics in patients presenting with sepsis or septic shock are associated with reduced mortality, and Surviving Sepsis Campaign guidelines recommend antibiotics within 1 h of recognition. Pharmacists are well‐equipped to help navigate the therapeutic and operational challenges associated with achieving this goal.

Objectives

To assess the association of pharmacist involvement in sepsis response with time to antibiotics in hospitalized patients with sepsis and septic shock.

Methods

A systematic review of the following databases was conducted: PubMed/MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. Studies must have included a designated role of an individual pharmacist in the management of sepsis or septic shock and not be considered an operational change. The primary outcome of interest was time to antibiotic administration, with secondary outcomes including intensive care unit (ICU) and hospital length of stay as well as in‐hospital mortality.

Results

We identified 10 studies including 1772 patients with sepsis or septic shock that evaluated a sepsis response in which a pharmacist was included. Studies included patients in the ICU, emergency department, and hospital ward setting. Seven studies demonstrated a significant reduction in time to antibiotics, with two other studies supporting this conclusion in extrapolation or sensitivity analysis. There was not a consistent reduction in ICU or hospital length of stay nor in‐hospital mortality between those interventions involving a pharmacist compared with their defined control groups.

Conclusion

Pharmacist involvement in sepsis response, often as part of a multiprofessional team‐based approach to sepsis care, is associated with a reduced time to antibiotic administration for hospitalized patients with sepsis or septic shock.
Morbidity of colectomy during pancreatoduodenectomy: An analysis of the pancreas‐targeted American College of Surgeons National Surgical Quality Improvement Program Registry
Authors: Harris Larkin B. , Osborn Tamara A. , Bennett Judy L. , Jensen Hanna K. , Giorgakis Emmanouil , Mavros Michail N.
Published: October 2022

Background

Pancreatoduodenectomy is a complex operation with considerable morbidity and mortality. Locally advanced tumors may require concurrent colectomy. We hypothesized that a concurrent colectomy increases the risk associated with pancreatoduodenectomy.

Methods

This retrospective review of the 2014–2019 pancreas‐targeted American College of Surgeons National Surgical Quality Improvement Program registry classified operations as pancreatoduodenectomy (PD) versus pancreatoduodenectomy/colectomy (PD+C). The two groups were compared with respect to demographics, comorbidities, disease characteristics, intraoperative variables, and postoperative outcomes. Main effect models were developed to examine the effect of concurrent colectomy on outcomes after adjusting for potential confounders.

Results

Of 24 421 pancreatoduodenectomies, 430 (1.8%) involved concurrent colectomy. PD + C patients had less comorbidities (obesity 19% vs. 27%, hypertension 43% vs. 53%, diabetes 20% vs. 26%) and were associated with malignant diagnosis (94% vs. 83%), vascular resection (28% vs. 18%), and longer operative time (median 6.9 vs. 6 h). On multivariable analysis, concurrent colectomy was independently associated with serious morbidity (adjusted odds ratio [OR] 2.62, 95% confidence interval [CI]: 1.94–3.54) but not mortality (OR 1.44 [0.63–3.31]).

Conclusions

Concurrent colectomy at the time of pancreatoduodenectomy significantly increased the odds of serious morbidity but did not affect mortality. This should be considered in operative planning, preoperative counseling, and sequencing of cancer‐directed treatments.
Inhibition of CGRP signaling impairs fracture healing in mice
Authors: Wee Natalie K. Y. , Novak Sanja , Ghosh Debolina , Root Sierra H. , Dickerson Ian M. , Kalajzic Ivo
Published: October 2022

Calcitonin gene‐related peptide (CGRP) is a neuropeptide produced by sensory nerves and functions as a pain sensor. It acts by binding to the calcitonin‐like receptor (CLR, protein; Calcrl, gene). CGRP inhibition has been recently introduced as therapeutic treatment of migraine‐associated pain. Previous studies have shown that CGRP stimulates bone formation. The aim of our study is to determine whether the inhibition of CGRP signaling negatively impacted fracture healing. Using α‐smooth muscle actin (αSMA) Cre animals crossed with Ai9 reporter mice, we showed that CGRP‐expressing nerves are near αSMA + cells in the periosteum. In vitro experiments revealed that periosteal cells express Calcrl and receptor activity modifying protein 1; and CGRP stimulation increased periosteal cell proliferation. Using a tamoxifen‐inducible model αSMACre/CLRfl/fl, we targeted the deletion of CLR to periosteal progenitor cells and examined fracture healing. Microcomputed tomography of fractured femurs showed a reduction in bone mass in αSMACre+/CLRfl/fl female mice relative to controls and callus volume in males. Pharmacological CGRP–CLR inhibition was achieved by subcutaneous delivery of customized pellets with small molecule inhibitor olcegepant (BIBN‐4096) at a dose of 10 μg/day. BIBN‐4096‐treated C57BL/6J mice had a higher latency toward thermal nociception than placebo‐treated mice, indicating impaired sensory function through CGRP inhibition. CGRP inhibition also resulted in reduced callus volume, bone mass, and bone strength compared to placebo controls. These results indicate that inhibiting CGRP by deleting CLR or by using BIBN‐4096, contributes to delayed bone healing.
Density functional theory demonstrates orientation effects in the Raman spectra of hydroxy‐ and carbonated apatite
Authors: Gemeri Dejan , Živković Aleksandar , Lukačević Igor , Bahmann Hilke , King Helen E.
Published: October 2022

Raman spectroscopy is widely used to examine the carbonate content within bone apatite, but Raman spectra are also sensitive to orientation effects between the polarisation of the incoming laser light and the sample orientation. This may lead to discrepancies when using Raman spectroscopy to evaluate the carbonate content as the extent of crystal organisation can change depending on the type of bone, age, and presence of mineralisation disorders in the organism. It is experimentally very challenging to evaluate the effect of orientation using individual bone crystals. Therefore, we have used density functional theory to examine the effect of orientation in apatitic materials. We examined hydroxyapatite and three different types of carbonated apatite: A‐type where the carbonate ion substitutes the two OH groups in the unit cell, B‐type where co‐substitution occurs between carbonate in a phosphate position and Na+ for Ca2+ to maintain charge balance, and AB‐type where carbonate sits in both A‐site and B‐site. Our simulations show that the OH group in hydroxyapatite has a strong orientation dependence, consistent with previous literature. In addition, the phosphate and carbonate bands of the apatitic structures are predicted to be orientation dependent, where the maximum scattering efficiency occurs in configurations in which the laser polarisation is parallel to the crystallographic axes of the material. The intensity changes of the phosphate and carbonate bands are not consistent upon changing orientations and thus may lead to an underestimation of carbonate contents if insufficient sampling points are used during bone analysis.
Application of Molecularly Imprinted Polymers in Plant Natural Products: Current Progress and Future Perspectives
Authors: Zuo Jiale , Ma Peirong , Li Zheng , Zhang Yanling , Xiao Douxin , Wu Haixia , Dong Alideertu
Published: October 2022

Plants, as a large and complex system, are rich in a variety of natural bioactive constituents. It is crucial to enrich, isolate, purify and detect these natural products. Molecularly imprinted polymers (MIPs) are a class of polymers prepared by molecularly imprinted technology (MIT) that have specific recognition sites and are complementary to templates in shape, size, and binding groups. The synthesis and polymerization mechanism of MIPs are introduced. A variety of preparation methods for MIPs have been developed. MIPs can be classified into three types: non‐covalent molecularly imprinted, covalent molecularly imprinted, and semi‐covalent molecularly imprinted. MIPs usually consists of five parts: template, functional monomer, cross‐linker, initiator, and solvent/reagent. With the advantages of high‐specificity binding ability, MIPs have shown excellent efficacy in the separation, enrichment, and purification of plant active products, such as flavonoids, polyphenols, terpenoids, and other components, especially as specific adsorbent materials. Due to the high selectivity to target the analytes, MIPs have also been used as sensors to detect the bioactive constituents in plants. Undeniably, MIPs still face undeniable limitations in the application of plant natural products. The development of MIPs with high selectivity, strong affinity, cost‐effectiveness, sensitivity, and environmental friendliness are valuable and promising.
Association of Coffee and Tea Consumption with Cardiovascular Disease, Chronic Respiratory Disease, and their Comorbidity
Authors: Chen Yanchun , Zhang Yuan , Yang Hongxi , Ma Yue , Zhou Lihui , Lin Jing , Hou Yabing , Yu Bin , Wang Yaogang
Published: October 2022

Scope

Since associations between coffee and tea consumption with cardiovascular disease (CVD) and chronic respiratory disease (CRD) remain controversial. This study aims to investigate the separate and combined associations of coffee and tea consumption with CVD, CRD, and their comorbidity.

Methods and results

Within the UK Biobank, 390 039 participants (56.2 ± 8.1 years) free of CVD and CRD are included. Coffee and tea consumption are self‐reported at baseline. During a median follow‐up of 12.1 years, 31126 CVD, 34132 CRD, and 6071 CVD‐CRD comorbidity cases are identified. J‐shaped associations between coffee and tea consumption with CVD, CRD, and CVD‐CRD comorbidity are observed (p for nonlinearity <0.001). Compared with neither coffee nor tea consumption, hazard ratios (HRs) and 95% confidence intervals (CIs) of combined consumption of moderate coffee and tea (each 2–3 cups per day) are 0.88 (0.81–0.96) for CVD, 0.78 (0.72–0.84) for CRD, and 0.74 (0.61–0.91) for CVD‐CRD comorbidity.

Conclusion

Moderate consumption of coffee and tea separately or in combination are associated with lower risks of CVD, CRD, and their comorbidity.
Interlaboratory comparison of voltage sweep methods used for the electrical characterization of encapsulated high‐efficiency c‐Si solar cells
Authors: Zhang Yating , Monokroussos Christos , Wilterdink Harrison , Müllejans Harald , Pavanello Diego , Yoshita Masahiro , Yamagoe Kengo , Ramspeck Klaus , Hinken David , Bothe Karsten , Fujita Yuji , Arnoux Gilles , Pinto Filipe , Ambigapathy Rajesh , Gao Qi , Shi Qiang , Chen Yi Feng , Ping Yan
Published: October 2022

This work presents the comparison of measurement results for four types of encapsulated high‐efficiency c‐Si solar cells measured by 10 laboratories based in Asia, Europe and North America utilizing a wide range of voltage sweeping methods, which include well‐established procedures that represent good industry practice, as well as recently introduced ones that have not been verified yet. The aim of the round‐robin interlaboratory comparison was to examine the measurement comparability of different laboratories with respect to their measurement methods of high‐efficiency solar cells. A proficiency test was employed to examine the consistency of results and their corresponding uncertainties. The short‐circuit current (ISC) under STC measured by four accredited laboratories was firstly compared. In order to investigate the consistency related to the high device capacitance, the value of the ISC was fixed for all 10 participants. The results of all participant laboratories—compared via En number analysis—generally remained well within [−1; 1], thus indicating consistency between the measured values and the reference values within stated measurement uncertainties. The differences remained within ±1.15% in PMAX and within ±0.35% in VOC for all participants and methods applied. Correlations were observed among the PMAX, VOC, and FF differences from their weighted mean. An analysis of the effects of transient current (dQ/dt) at maximum power point caused by hysteresis effect on the measurement error of PMAX showed a significant linear correlation between error of maximum power and junction voltage sweep rate for heterojunction (HJT) solar cells. This work forms the basis to validate all applied methods and their stated measurement uncertainties.
Study on a Novel Synthetic Route and Properties of 1‐trinitromethyl‐3‐nitro‐1,2,4‐triazole (TNMNT)
Authors: Yanwu Yu , Yuan Guo , Haodong Zhao , Hongbin Wang , Hui Ma , Jiahu Guo , Suming Jing , Guimin Cheng , Xiaodan Wang , Yuanfeng Zhao
Published: October 2022

Materials with low melting point and high energy density have become the focus of research on energy‐containing materials thanks to their superb detonation performance and wide applications. This paper proposed a new synthetic route for an energy‐containing compound 1‐trinitromethyl‐3‐nitro‐1,2,4‐triazole (TNMNT), using 3‐nitro‐1,2,4‐triazole as the raw material, low toxic chloroacetone as the substitute and KBr as the catalyst. These substances reacted at 70 °C for 3 h in a DMF reaction solvent system. The intermediate 1‐acetonyl‐3‐nitro‐1,2,4‐triazole (ANT) was obtained with a yield of 38 %. The nitration process increased the volume ratio of mixed nitric and sulfuric acids (1 : 3), and the reaction time was 36 h. TNMNT as a nitrogen‐rich compound having low melting point and high energy density was synthesized with a yield of 43 %. Compared with the traditional process, the experimental period was significantly shortened, and this synthetic method proved more environment‐friendly. Scanning Electron Microscopy (SEM), Differential Scanning Calorimeter (DSC) and mechanical sensitivity tests were performed on the products. It was found that the melting and decomposition points of TNMNT were 100.5 °C and 166.4 °C, respectively, the characteristic drop height H50 was 21.3 cm, and the frictional sensitivity was 56 %. Results show that the TNMNT crystals synthesized by this new route have better morphology, higher purity, and lower melting point. Compared with the raw material, the introduction of the trinitromethyl group produced higher mechanical sensitivity than other compounds having low melting point. Calculation of the thermal decomposition parameters found: activation energy of 104.4 kJ ⋅ mol−1, pre‐exponential factor of 2.27×1010 s−1, activation enthalpy of 100.9 kJ ⋅ mol−1, activation entropy of 57.98 J ⋅ mol−1 ⋅ K−1, and activation free energy of 125.72 kJ ⋅ mol−1.
RCSB Protein Data bank: Tools for visualizing and understanding biological macromolecules in 3D
Authors: Burley Stephen K. , Bhikadiya Charmi , Bi Chunxiao , Bittrich Sebastian , Chao Henry , Chen Li , Craig Paul A. , Crichlow Gregg V. , Dalenberg Kenneth , Duarte Jose M. , Dutta Shuchismita , Fayazi Maryam , Feng Zukang , Flatt Justin W. , Ganesan Sai J. , Ghosh Sutapa , Goodsell David S. , Green Rachel Kramer , Guranovic Vladimir , Henry Jeremy , Hudson Brian P. , Khokhriakov Igor , Lawson Catherine L. , Liang Yuhe , Lowe Robert , Peisach Ezra , Persikova Irina , Piehl Dennis W. , Rose Yana , Sali Andrej , Segura Joan , Sekharan Monica , Shao Chenghua , Vallat Brinda , Voigt Maria , Webb Benjamin , Westbrook John D. , Whetstone Shamara , Young Jasmine Y. , Zalevsky Arthur , Zardecki Christine
Published: October 2022

Now in its 52nd year of continuous operations, the Protein Data Bank (PDB) is the premiere open‐access global archive housing three‐dimensional (3D) biomolecular structure data. It is jointly managed by the Worldwide Protein Data Bank (wwPDB) partnership. The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) is funded by the National Science Foundation, National Institutes of Health, and US Department of Energy and serves as the US data center for the wwPDB. RCSB PDB is also responsible for the security of PDB data in its role as wwPDB‐designated Archive Keeper. Every year, RCSB PDB serves tens of thousands of depositors of 3D macromolecular structure data (coming from macromolecular crystallography, nuclear magnetic resonance spectroscopy, electron microscopy, and micro‐electron diffraction). The RCSB PDB research‐focused web portal (RCSB.org) makes PDB data available at no charge and without usage restrictions to many millions of PDB data consumers around the world. The RCSB PDB training, outreach, and education web portal (PDB101.RCSB.org) serves nearly 700 K educators, students, and members of the public worldwide. This invited Tools Issue contribution describes how RCSB PDB (i) is organized; (ii) works with wwPDB partners to process new depositions; (iii) serves as the wwPDB‐designated Archive Keeper; (iv) enables exploration and 3D visualization of PDB data via RCSB.org; and (v) supports training, outreach, and education via PDB101.RCSB.org. New tools and features at RCSB.org are presented using examples drawn from high‐resolution structural studies of proteins relevant to treatment of human cancers by targeting immune checkpoints.
Relativistic Krori‐Barua Compact Stars in f(R,T)$f(R,T)$ Gravity
Authors: Shamir M. Farasat , Asghar Zoya , Malik Adnan
Published: October 2022

This work aims to investigate the behaviour of compact stars in the background of theory of gravity. For current work, we consider the Krori‐Barua metric potential i.e., and , where, and C are constants. We use matching conditions of spherically symmetric space‐time with Schwarzschild solution as an exterior geometry and examine the physical behaviour of stellar structure by assuming the exponential type gravity model. In the present analysis, we discuss the graphical behaviour of energy density, radial pressure, tangential pressure, equation of state parameters, anisotropy and stability analysis respectively. Furthermore, an equilibrium condition can be visualized through the modified Tolman‐Oppenheimer‐Volkov equation. Some extra features of compact stars i.e. mass‐radius function, compactness factor and surface redshift have also been investigated. Conclusively, all the results in current study validate the existence of compact stars under exponential gravity model.
Mass Hierarchies and Quantum Gravity Constraints in DKMM‐refined KKLT
Authors: Blumenhagen Ralph , Gligovic Aleksandar , Kaddachi Seyf
Published: October 2022

We carefully revisit the mass hierarchies for the KKLT scenario with an uplift term from an anti D3‐brane in a strongly warped throat. First, we derive the bound resulting from what is usually termed “the throat fitting into the bulk” directly from the Klebanov‐Strassler geometry. Generating the small value of the superpotential W0 via the mechanism proposed by Demirtas, Kim, McAllister and Moritz (DKMM), we identify two possible DKMM‐refined KKLT scenarios for stabilizing the light axio‐dilaton modulus. The first scenario spoils the expected hierarchy between the bulk and the throat mass scales and implies that the energy scale of the uplift is larger than the species scale of the effective theory in the throat. Moreover it requires an unnaturally large tadpole that is certainly in conflict with tadpole cancellation. For the less restricted second scenario, the hierarchy can be controlled at the expense of, under the most optimistic assumptions, an only moderately large tadpole .
Effect of Deposition Flux on Polytypic Competitive Growth of SiC Crystal by Kinetic Monte Carlo Method
Authors: Chen Xuejiang , Xia Qian , Zhao Hao , Ai Wensen
Published: October 2022

A competitive kinetic Monte Carlo (KMC) model for gas‐phase epitaxy growth of 4H‐SiC and 6H‐SiC crystals is established based on polytype transformation and the Monte Carlo algorithm. The competitive growth processes of the two polytypes are simulated, and the effect of deposition flux on the polytype competition is analyzed. The 4H‐SiC competitive growth is promoted by the increase in deposition rate, and the effect of the Si/C ratio on polytypic competition is suppressed by the high deposition rate. Moreover, competitive growth is affected by deposition flux by changing the ratio of diffusion rate to deposition rate.
Juglone promotes antitumor activity against prostate cancer via suppressing glycolysis and oxidative phosphorylation
Authors: Hu Cheng , Xu Haiyue , Li Zehao , Liu Dandan , Zhang Siqi , Fang Fang , Wang Liguo
Published: October 2022

The treatments currently used for prostate cancer (PC) do not meet clinical needs, and thus, new therapies with greater effectiveness are urgently required. Metabolic reprogramming of tumor cells is emerging as an exciting field for cancer therapy. Although the Warburg effect is a common feature of glucose metabolism in many cancers, PC cells have a unique metabolic phenotype. Non‐neoplastic prostate cells show reduced oxidative phosphorylation (OXPHOS) because large, accumulated zinc inhibits citrate oxidation. During transformation, there are low levels of zinc in PC cells, and the tricarboxylic acid (TCA) cycle is reactivated. However, metastatic PC exhibits the Warburg effect. Due to metabolic differences in prostate tissue, targeting metabolic alterations in PC cells is an attractive therapeutic strategy. In this study, we investigated the effect of juglone on energy metabolism in PC cells. We found that juglone inhibited cell proliferation and induced apoptosis. Mechanistically, we demonstrated that juglone suppressed OXPHOS and glycolysis due to its inhibition of hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK) activity. Furthermore, downregulation of PFK and PK, but not HK contributed to the inhibition of these enzyme activities. The current study indicates that further development of juglone for PC treatment would be beneficial.
Improved off‐policy reinforcement learning algorithm for robust control of unmodeled nonlinear system with asymmetric state constraints
Authors: Zhang Yong , Mu Chaoxu , Feng Yanghe , Zhao Zhijia
Published: October 2022

In this article, an improved data‐based off‐policy reinforcement learning algorithm is proposed for the robust control of unmodeled nonlinear systems with asymmetric state constraints. An improved nonlinear mapping is defined for the asymmetric state constraint problem, which can ensure that the mapping state has better response speed and amplitude than the original state. Then, an auxiliary mapping error system is constructed for the off‐policy robust controller design. At the same time, an innovative network dimensionality reduction method based on principal component analysis is proposed to simplify the useless activation function of action network in off‐policy algorithm, which can effectively reduce the computational burden of data episodes. Considering the uncertain data caused by disturbances, a dominant data sampling method is designed to extract samples that are beneficial to algorithm convergence. On this basis, the improved off‐policy robust control algorithm is constructed. Based on an industrial manipulator system, the effectiveness of the dominant data sampling method and the improved off‐policy robust control algorithm is verified by comparative simulation.
Free water derived by multi‐shell diffusion MRI reflects tau/neuroinflammatory pathology in Alzheimer's disease
Authors: Nakaya Moto , Sato Noriko , Matsuda Hiroshi , Maikusa Norihide , Shigemoto Yoko , Sone Daichi , Yamao Tensho , Ogawa Masayo , Kimura Yukio , Chiba Emiko , Ohnishi Masahiro , Kato Koichi , Okita Kyoji , Tsukamoto Tadashi , Yokoi Yuma , Sakata Masuhiro , Abe Osamu
Published: October 2022

Introduction

Free‐water (FW) imaging, a new analysis method for diffusion magnetic resonance imaging (MRI), can indicate neuroinflammation and degeneration. We evaluated FW in Alzheimer's disease (AD) using tau/inflammatory and amyloid positron emission tomography (PET).

Methods

Seventy‐one participants underwent multi‐shell diffusion MRI, 18F‐THK5351 PET, 11C‐Pittsburgh compound B PET, and neuropsychological assessments. They were categorized into two groups: healthy controls (HCs) (n = 40) and AD‐spectrum group (AD‐S) (n = 31) using the Centiloid scale with amyloid PET and cognitive function. We analyzed group comparisons in FW and PET, correlations between FW and PET, and correlation analysis with neuropsychological scores.

Results

In AD‐S group, there was a significant positive correlation between FW and 18F‐THK5351 in the temporal lobes. In addition, there were negative correlations between FW and cognitive function in the temporal lobe and cingulate gyrus, and negative correlations between 18F‐THK5351 and cognitive function in the same regions.

Discussion

FW imaging could be a biomarker for tau in AD alongside clinical correlations.
miR‐1246 is implicated as a possible candidate for endometrium remodelling facilitating implantation in buffalo (Bubalus bubalis)
Authors: Dubey Pratiksha , Batra Vipul , Sarwalia Parul , Nayak Samiksha , Baithalu Rubina , Kumar Rakesh , Datta Tirtha Kumar
Published: October 2022

Background

The microRNAs (miRs) secreted by the trophectoderm (TE) cells have recently been implicated in the conceptus‐endometrial cross talk during implantation and placentation. These miRs modulate various cellular processes during conception and throughout the pregnancy by regulating the gene expression in the foetal and maternal tissues.

Objectives

This study was undertaken to elucidate the function of TE secreted miRNAs in the maternal‐foetal cross‐talk during implantation/placentation in buffalo.

Methods

The in vitro produced blastocysts were cultured on a cumulus feeder layer for 21 days. The relative expression profiles of a selected panel of miRs was generated using the spent media collected on Days 0, 7, 12, 16, and 21. A custom‐designed mirVana™ miRNA mimic was used to transfect the endometrial epithelial cells (EECs) in order to determine the role of miRNA exhibiting highest expression on Days 21 and 21.

Results

The expression of miR‐1246 (p < 0.001) and let‐7b (p < 0.01) was found to be significantly higher on Day 21 of TE culture in comparison to the control (Day 0). This elevated expression indicated the involvement of these miRs in the maternal‐foetal cross‐talk. Interestingly, after the transfection of EECs with miRNA mimic for miR‐1246 (a novel molecule vis‐à‐vis implantation), the expression of beta‐catenin and mucin1 in these cells was found to be significantly (p < 0.05) downregulated vis‐à‐vis the control, that is, the IFN‐τ primed EECs (before transfection).

Conclusions

The TE secreted miR‐1246 appeared to lower the expression of the endometrial receptivity genes (mucin1 and beta‐catenin) which apparently assists the endometrium in preparing for placentation.
Non-relativistic and ultra-relativistic expansions of three-dimensional spin-3 gravity theories
Authors: Concha Patrick , Henríquez-Baez Carla , Rodríguez Evelyn
Published: October 2022

Abstract

In this paper, we present novel and known non-relativistic and ultra-relativistic spin-3 algebras, by considering the Lie algebra expansion method. We start by applying the expansion procedure using different semigroups to the spin-3 extension of the AdS algebra, leading to spin-3 extensions of known non-relativistic and ultra-relativistic algebras. We then generalize the procedure considering an infinite-dimensional semigroup, which allows to obtain a spin-3 extension of two new infinite families of the Newton-Hooke type and AdS Carroll type. We also present the construction of the gravity theories based on the aforementioned algebras. In particular, the expansion method based on semigroups also allows to derive the (non-degenerate) invariant bilinear forms, ensuring the proper construction of the Chern-Simons gravity actions. Interestingly, in the vanishing cosmological constant limit we recover the spin-3 extensions of the infinite-dimensional Galilean and infinite-dimensional Carroll gravity theories.
Basal Gp78-dependent mitophagy promotes mitochondrial health and limits mitochondrial ROS
Authors: Alan Parsa , Vandevoorde Kurt R. , Joshi Bharat , Cardoen Ben , Gao Guang , Mohammadzadeh Yahya , Hamarneh Ghassan , Nabi Ivan R.
Published: October 2022

Mitochondria are major sources of cytotoxic reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, that when uncontrolled contribute to cancer progression. Maintaining a finely tuned, healthy mitochondrial population is essential for cellular homeostasis and survival. Mitophagy, the selective elimination of mitochondria by autophagy, monitors and maintains mitochondrial health and integrity, eliminating damaged ROS-producing mitochondria. However, mechanisms underlying mitophagic control of mitochondrial homeostasis under basal conditions remain poorly understood. E3 ubiquitin ligase Gp78 is an endoplasmic reticulum membrane protein that induces mitochondrial fission and mitophagy of depolarized mitochondria. Here, we report that CRISPR/Cas9 knockout of Gp78 in HT-1080 fibrosarcoma cells increased mitochondrial volume, elevated ROS production and rendered cells resistant to carbonyl cyanide m-chlorophenyl hydrazone (CCCP)-induced mitophagy. These effects were phenocopied by knockdown of the essential autophagy protein ATG5 in wild-type HT-1080 cells. Use of the mito-Keima mitophagy probe confirmed that Gp78 promoted both basal and damage-induced mitophagy. Application of a spot detection algorithm (SPECHT) to GFP-mRFP tandem fluorescent-tagged LC3 (tfLC3)-positive autophagosomes reported elevated autophagosomal maturation in wild-type HT-1080 cells relative to Gp78 knockout cells, predominantly in proximity to mitochondria. Mitophagy inhibition by either Gp78 knockout or ATG5 knockdown reduced mitochondrial potential and increased mitochondrial ROS. Live cell analysis of tfLC3 in HT-1080 cells showed the preferential association of autophagosomes with mitochondria of reduced potential. Xenograft tumors of HT-1080 knockout cells show increased labeling for mitochondria and the cell proliferation marker Ki67 and reduced labeling for the TUNEL cell death reporter. Basal Gp78-dependent mitophagic flux is, therefore, selectively associated with reduced potential mitochondria promoting maintenance of a healthy mitochondrial population, limiting ROS production and tumor cell proliferation.
Bibliometric development of Naunyn–Schmiedeberg’s Archives of Pharmacology
Authors: Dats Leah B. , von Haugwitz Florentin , Seifert Roland
Published: October 2022

Motivated by the 150-year anniversary of the Naunyn–Schmiedeberg’s Archives of Pharmacology in 2023, we studied the bibliometric development of the journal. We evaluated data from Editorial Reports, Clarivate, and Springer Nature databases. Several parameters representing the journal’s performance, such as the impact factor and social impact, were analyzed over the years. We analyzed the journal’s meta-data and wrote an algorithm to retrieve cities and countries of origin. We could see a decrease in publications from Germany and an increase in papers from Brazil, China, Egypt, and Iran during the last years. The decrease in publications from Germany is probably a zeitgeist effect because this country places a strong emphasis on high-impact factor papers for academic promotion and winning grants. Germany was the country with the most publications throughout the 100 most-cited articles. Most of these articles were published between 1970 and 1990, when neurotransmitters were the most published topic. Klaus Starke (Freiburg) and Manfred Göthert (Bonn) were prominent drivers of this field. The most common topics nowadays are “Drugs for the Treatment of Malignant Tumor Diseases” and “Immunopharmacology.” The internationality of the journal substantially increased after introduction of English as mandatory language in the 1970s. The journal also experienced substantial COVID-19 pandemic-related effects. This paper is not only of relevance for the field of pharmacology but for science in general in the sense that Naunyn–Schmiedeberg’s Archives of Pharmacology is a case study for profound changes in a traditional scientific journal, requiring permanent adjustment by editors, referees, publisher, authors, and readers alike. The development of the journal has been strongly influenced by historic and political developments, cultural attitudes (zeitgeist), language changes, global changes in research topics, and eminent individuals who published many papers in Naunyn–Schmiedeberg’s Archives of Pharmacology.
Production of propionate using metabolically engineered strains of Clostridium saccharoperbutylacetonicum
Authors: Baur Tina , Wentzel Alexander , Dürre Peter
Published: October 2022

The carboxylic acid propionate is a valuable platform chemical with applications in various fields. The biological production of this acid has become of great interest as it can be considered a sustainable alternative to petrochemical synthesis. In this work, Clostridium saccharoperbutylacetonicum was metabolically engineered to produce propionate via the acrylate pathway. In total, the established synthetic pathway comprised eight genes encoding the enzymes catalyzing the conversion of pyruvate to propionate. These included the propionate CoA-transferase, the lactoyl-CoA dehydratase, and the acryloyl-CoA reductase from Anaerotignum neopropionicum as well as a D-lactate dehydrogenase from Leuconostoc mesenteroides subsp. mesenteroides. Due to difficulties in assembling all genes on one plasmid under the control of standard promoters, the PtcdB-tcdR promoter system from Clostridium difficile was integrated into a two-plasmid system carrying the acrylate pathway genes. Several promoters were analyzed for their activity in C. saccharoperbutylacetonicum using the fluorescence-activating and absorption-shifting tag (FAST) as a fluorescent reporter to identify suitable candidates to drive tcdR expression. After selecting the lactose-inducible PbgaL promoter, engineered C. saccharoperbutylacetonicum strains produced 0.7 mM propionate upon induction of gene expression. The low productivity was suspected to be a consequence of a metabolic imbalance leading to acryloyl-CoA accumulation in the cells. To even out the proposed imbalance, the propionate-synthesis operons were rearranged, thereby increasing the propionate concentration by almost four-fold. This study is the first one to report recombinant propionate production using a clostridial host strain that has opened a new path towards bio-based propionate to be improved further in subsequent work.

Key points

• Determination of promoter activities in C. saccharoperbutylacetonicum using FAST.

• Implementation of propionate production in C. saccharoperbutylacetonicum.

• Elevation of propionate production by 375% to a concentration of 3 mM.
Current Knowledge and Future Perspectives of Buttock Augmentation: A Bibliometric Analysis from 1999 to 2021
Authors: Dai Yuxuan , Chen Yu , Hu Yiming , Zhang Lianbo
Published: October 2022

Background

The number of patients undergoing buttock augmentation surgery has increased rapidly with time, changes in people’s aesthetic perceptions, and the increased concern for their shape. The number of publications regarding buttock augmentation has also continued to increase. However, no bibliometric analysis concerning buttock augmentation has been published. This study aimed to provide a qualitative and quantitative evaluation of buttock augmentation-related publications using bibliometric analysis and information on research hotspots and trends in this field.

Methods

The buttock augmentation-related publications published between 1999 and 2021 were extracted from the Web of Science Core Collection (WOSCC) database for analysis. The data were analysed and presented using VOSviewer and Microsoft Excel.

Results

There were 492 articles in the (WOSCC) database, including 442 (89.84%) original research articles, with the number of publications increasing each year. The USA (208 publications, 42.28%) is the leading contributor in this field and has a high academic reputation. The most productive and co-cited journal on this subject is “Plastic and Reconstructive Surgery” (66 publications, 13.41%, 2200 citations). Cardenas-Camarena (9 publications, 1.83%, 158 citations) was the most published and co-cited author. Research hotspots include the following three topics: experience and technology of buttock augmentation, autologous fat buttock augmentation and its safety, and buttock aesthetics study. There will be more publications in the future, and research trends will focus on silicone implants, safety, satisfaction, and autologous fat grafting.

Conclusion

Buttock augmentation research is rapidly evolving, and this study provides a perspective view of buttock augmentation research in Plastic and Reconstructive Surgery.

Level of Evidence III

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
The Decrease in Serum sRAGE Levels Upon Smoking is Associated with Activated Neutrophils
Authors: Wiersma Valerie R. , Hoonhorst Susan J. M. , ten Hacken Nick H. T. , van den Berge Maarten , Slebos Dirk-Jan , Pouwels Simon D.
Published: October 2022

The serum level of the soluble Receptor for Advanced Glycation End-products (sRAGE) is a promising blood biomarker for the development, severity, and progression of chronic obstructive pulmonary disease (COPD). However, cigarette smoking causes a nearly instant drop in circulating sRAGE levels, strongly impacting on the variability in sRAGE levels. In the current study, we investigated the possible mechanism behind the sudden drop in sRAGE upon smoking. We showed that the number of activated neutrophils in blood significantly increases within two hours upon smoking three cigarettes within one hour. Furthermore, an increased expression of the leukocyte activation marker CD11b, which is a known ligand for RAGE, was observed upon smoking. Additionally, the in vitro activation of neutrophils increased their capacity to bind sRAGE. Together, these data indicate that smoking activates neutrophils in the circulation with concomitant upregulation of the RAGE ligand CD11b, leading to reduced levels of sRAGE in serum.
The prediction method for standard enthalpies of apatites using the molar volume, lattice energy, and linear correlations from existing experimental data
Authors: Puzio Bartosz , Manecki Maciej
Published: October 2022

Experimental data of thermodynamic state functions and molar volume for phosphate, arsenate, and vanadate apatites containing Ca, Sr, Ba, Pb, end Cd at the cationic positions Me2+ and F, OH, Cl, Br, and I at the halide position X were collected. The apatite supergroup splits into distinct subgroups (populations) constituted by Me10(AO4)6X2 with the same Me2+ cations and tetrahedral AO43− anions but with different anions at the X position. Linear relationships between various parameters within apatite subgroups are observed. The prediction method for standard enthalpies of apatites (ΔHºf,el) is based on regression analysis of the linear correlations within the subgroups between ΔH°f,el of apatites and their molar volume Vm, lattice energy UPOT, and ΔH°f,el of their anions AO43− or X−. This allowed to predict 22 new ΔH°f,el values for apatites and materials with an apatite structure. The prediction precision is comparable to the experimental uncertainty obtained when reproducing experimental data using calorimetric measurements or dissolution experiments and can be applied to a wider range of apatites than other methods.
No effect of repeated post-resistance exercise cold or hot water immersion on in-season body composition and performance responses in academy rugby players: a randomised controlled cross-over design
Authors: Horgan Barry G. , Halson Shona L. , Drinkwater Eric J. , West Nicholas P. , Tee Nicolin , Alcock Rebekah D. , Chapman Dale W. , Haff G. Gregory
Published: October 2022

Purpose

Following resistance exercise, uncertainty exists as to whether the regular application of cold water immersion attenuates lean muscle mass increases in athletes. The effects of repeated post-resistance exercise cold versus hot water immersion on body composition and neuromuscular jump performance responses in athletes were investigated.

Methods

Male, academy Super Rugby players (n = 18, 19.9 ± 1.5 y, 1.85 ± 0.06 m, 98.3 ± 10.7 kg) participated in a 12-week (4-week × 3-intervention, i.e., control [CON], cold [CWI] or hot [HWI] water immersion) resistance exercise programme, utilising a randomised cross-over pre–post-design. Body composition measures were collected using dual-energy X-ray absorptiometry prior to commencement and every fourth week thereafter. Neuromuscular squat (SJ) and counter-movement jump (CMJ) performance were measured weekly. Linear mixed-effects models were used to analyse main (treatment, time) and interaction effects.

Results

There were no changes in lean (p = 0.960) nor fat mass (p = 0.801) between interventions. CON (p = 0.004) and CWI (p = 0.003) increased (g = 0.08–0.19) SJ height, compared to HWI. There were no changes in CMJ height (p = 0.482) between interventions.

Conclusion

Repeated post-resistance exercise whole-body CWI or HWI does not attenuate (nor promote) increases in lean muscle mass in athletes. Post-resistance exercise CON or CWI results in trivial increases in SJ height, compared to HWI. During an in-season competition phase, our data support the continued use of post-resistance exercise whole-body CWI by athletes as a recovery strategy which does not attenuate body composition increases in lean muscle mass, while promoting trivial increases in neuromuscular concentric-only squat jump performance.