bluuebunny/crossref_metadata_2025 huggingface dataset:
A Rationally Designed Bimetallic Platinum (II)‐Ferrocene Antitumor Agent Induces Non‐Apoptotic Cell Death and Exertsin VivoEfficacy
Authors: Gadre Shubhankar , Manikandan M. , Duari Prakash , Chhatar Sushant , Sharma Astha , Khatri Subhash , Kode Jyoti , Barkume Madan , Kasinathan Nirmal Kumar , Nagare Manasi , Patkar Meena , Ingle Arvind , Kumar Mukesh , Kolthur‐Seetharam Ullas , Patra Malay
Published: May 2022

Despite phenomenal clinical success, the efficacy of platinum anticancer drugs is often compromised due to inherent and acquired drug resistant phenotypes in cancers. To circumvent this issue, we designed two heterobimetallic platinum (II)‐ferrocene hybrids that display multi‐pronged anticancer action. In cancer cells, our best compound,2, platinates DNA, produces reactive oxygen species, and has nucleus, mitochondria, and endoplasmic reticulum as potential targets. The multi‐modal mechanism of action of these hybrid agents lead to non‐apoptotic cell death induction which enables circumventing apoptosis resistance and significant improvement in platinum cross resistance profile. Finally, in addition to describing detail mechanistic insights, we also assessed its stability in plasma and demonstrate anticancer efficacy in an in vivo A2780 xenograft model. Strikingly, compared to oxaliplatin, our compound displays better tolerability, safety profile and efficacy in vivo.
Study of Carbamoyl Fluoride: Synthesis, Properties and Applications
Authors: Bonnefoy Clémence , Chefdeville Emmanuel , Tourvieille Christian , Panossian Armen , Hanquet Gilles , Leroux Frédéric , Toulgoat Fabien , Billard Thierry
Published: May 2022

Carbamoyl fluoride is a fluorinated group that, to this date, remains underexplored, probably due to the lack of data concerning its properties. In this paper, a study of carbamoyl fluoride is presented. Stability studies, in particular under physiological conditions, and lipophilicity measurement were performed. A new easy, safe, inexpensive, and metal‐free synthesis method is also described. Finally, a potential use in radiochemistry through a 18F/19F isotopic exchange is demonstrated.
Experimental investigation on drying performance of pharmaceutical granules in a pulsation‐assisted fluidized bed dryer
Authors: Li Chen , Blocka Carter , Zhang Lifeng
Published: May 2022

Fluidized bed drying has been widely employed in pharmaceutical manufacturing processes. Due to the considerable cohesiveness of wet pharmaceutical granules, channelling phenomena pose significant challenges to fluidization and drying. In this work, the drying performance of pharmaceutical granules in a pulsation‐assisted fluidized bed dryer was experimentally investigated. The drying rate and energy efficiency were investigated with representative pharmaceutical powders, including active pharmaceutical ingredients (APIs). It is found that the pulsed airflow is effective in enhancing the drying rate at higher superficial gas velocity. A lower pulsation frequency is more favourable to improve the drying rate. During the constant rate period, energy efficiency is between 60% and 45% for the drying process, while the energy efficiency decreases to 10% during the falling rate period. A pulsed fluidized bed dryer has shown a higher energy efficiency than a conventional one with a constant air flow. Among nine thin‐layer drying models examined in this work, the Midilli and Kucuk model has shown the best agreement between the experimental data and the predicted results.
Improving in vivo Uranyl Removal Efficacy of a Nano‐Metal Organic Framework by Interior Functionalization with 3‐Hydroxy‐2‐pyridinone
Authors: Chen Mengping , Lang Lang , Chen Lei , Wang Xiaomei , Shi Cen , Sun Qiwen , Xu Yigong , Diwu Juan , Wang Shuao
Published: May 2022

Comprehensive Summary

The environmental contamination of uranium will occur in scenarios such as nuclear accidents and leakage from nuclear waste storage sites, which eventually leads to the internal uranium exposure of people, causing consequential injuries of renal failure, osteosarcoma, etc. The development of uranyl specific chelating agents that could sequester uranium in vivo is in urgent need and is important for the safe and efficient development of nuclear industry. Metal organic frameworks (MOFs) already serve as efficient uranium depletion materials in solutions of a wide range of pH and ionic strength for nuclear fuel recycling, uranium extraction from seawater, as well as environmental decontamination. Herein, a chromium‐based nano‐metal organic framework (nano‐MOF) functionalized interiorly with 3,2‐HOPO ligands, MIL‐101‐HOPO, is rationally synthesized. In vitro adsorption experiments show that MIL‐101‐HOPO exhibits high adsorption selectivity and fast adsorption kinetics for uranyl. The results of in vivo uranyl decorporation assays reveal that MIL‐101‐HOPO with the decoration of HOPO ligands on the interior wall exhibits significantly increased uranyl removal ratio in kidneys comparing to the pristine nMOFs, and is more effective than the clinically used ZnNa3‐DTPA. All those results corroborate the interior functionalization of MOFs as an efficient strategy to develop promising uranyl decorporation agents.
Assessment of clinical trial protocols for pathology content using the SPIRIT‐Path guidelines highlights areas for improvement
Authors: Robinson Peter , Bacon Chris M , Lim Shujing J , Shaaban Abeer M , Brierley Daniel , Lewis Ian , Harrison David J , Kendall Timothy J , Robinson Max
Published: May 2022

The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement provides evidence‐based recommendations for the minimum content of clinical trial protocols. The Cellular Molecular Pathology Initiative, hosted by the UK National Cancer Research Institute, developed an extension, SPIRIT‐Path, describing how to effectively incorporate pathology support into clinical trial protocols. The current study assessed the inclusion of SPIRIT‐Path items in protocols of active clinical trials. Publicly available clinical trial protocols were identified for assessment against the new guidelines using a single UK hospital as the ‘test site’. One hundred and ninety interventional clinical trials were identified as receiving support from the pathology department. However, only 38 had publicly available full trial protocols (20%) and following application of the inclusion/exclusion criteria, 19 were assessed against the SPIRIT‐Path guidelines. The reviewed clinical trial protocols showed some areas of compliance and highlighted other items that were inadequately described. The latter lacked information about the individuals responsible for the pathology content of the trial protocol, how pathology activities and roles were organised in the trial, where the laboratory work would be carried out, and the accreditation status of the laboratory. Only one trial had information specific to digital pathology, a technology certain to become more prevalent in the future. Adoption of the SPIRIT‐Path checklist will facilitate comprehensive trial protocols that address all the key cellular and molecular pathology aspects of interventional clinical trials. This study highlights once again the lack of public availability of trial protocols. Full trial protocols should be available for scrutiny by the scientific community and the public who participate in the studies, increasing the transparency of clinical trial activity and improving quality.
Tropospheric attenuation prediction for future millimeter wave terrestrial systems: Estimating statistics and extremes
Authors: Liu Jinwen , Matolak David W. , Güvenç Ismail , Mehrpouyan Hani
Published: May 2022

Tropospheric attenuations can be significant in the millimeter wave (mmWave) frequency bands; hence, accurate prediction modeling of tropospheric attenuation is important for reliable mmWave communication. Several models have been established by the International Telecommunication Union (ITU), yet estimation accuracy is limited due to the large spatial scales used for model input parameters. In this paper, we address this and apply local precipitation data to analyze tropospheric attenuation statistics and compare to results when using ITU regional input rain data. Specifically, tropospheric attenuation is predicted via simulations using the ITU method at 30, 60, and 90 GHz in four distinct geographic locations with different climate types. From our simulations, we gather statistics for annual average rain attenuation, worst month rain attenuation, and rain attenuation per decade. Our results indicate that when using local measured rain data, for 1 km link distance, mean rain event attenuation increases from 0.5 to 2 dB. Local rain data yield larger attenuations at essentially all percentages of time not exceeded (essentially corresponding to all probability values): for example, for 0.1% of time not exceeded, in Columbia, SC, rain attenuation for 30 GHz frequency increases to 9 dB with local rain data, compared to 5 dB with ITU's regional data, corresponding to rain rates of 38.2 and 17.5 mm/h, respectively; at the same probability and location, the 90 GHz attenuation increases by 10 dB, from 10 to 20 dB when local rain data are used. Fog attenuations are also appreciable, reaching 8 dB for the 90 GHz frequency. Moreover, for the example locations, peak rain attenuations have increased at a rate of approximately 2 dB/decade over the past 50 years. Our results indicate that actual tropospheric attenuations may be substantially larger than that predicted by the ITU model when using regional rain rate data.
An SS18::NEDD4 cutaneous spindled and epithelioid sarcoma: An hitherto unclassified cutaneous sarcoma, resembling epithelioid sarcoma with aggressive clinical behavior
Authors: Patton Ashley , Oghumu Steve , Iwenofu O. Hans
Published: May 2022

SS18::SSX gene fusions as a result of t(X,18)(p11;q11) have only been described in synovial sarcoma (SS). Recently, an SS18::NEDD4 gene fusion was identified in a single case of primary renal SS exhibiting a hypocellular and myxoid morphology. Herein, we report a case of an unclassified malignant cutaneous spindled and epithelioid neoplasm in a 60‐year‐old female that resembled an epithelioid sarcoma (ES) and harbored a rare SS18::NEDD4 gene fusion. Briefly, the patient presented with a progressively growing cutaneous mass involving the volar aspect of right hand, warranting an amputation. Histologic sections revealed a cutaneous ulcerative neoplasm composed of spindled and epithelioid cells, bearing a certain semblance to ES, with diffuse invasion into the subcutis and skeletal muscle. Coagulation tumor necrosis and mitotic figures were present. By immunohistochemistry, the tumor cells were positive for keratins (AE1/3 and cam5.2), vimentin, CMYC, BCL2, p53, smooth muscle actin (focal), and TLE1 (multifocal) and negative for p40, p63, CK5/6, CK7, CK20, CD56, CD31, CD34, ERG, desmin, SMMS, H‐Caldesmon, myogenin, and S‐100. Expression of INI1 stain was retained. The unusual histomorphology and inconclusive immunophenotypic profile lead to next‐generation sequencing identifying an SS18::NEDD4 gene fusion with genomic coordinates 5′‐SS18 (ex1‐9 NM_005637)‐NEDD4 (ex14‐29 NM_006154). Fluorescence in situ hybridization confirmed SS18 gene rearrangement. Within 2 years, the patient developed widespread metastatic disease. Despite aggressive multimodality treatment, the patient succumbed to disease. In summary, we report a unique case of previously unclassified cytokeratin positive malignant cutaneous spindled and epithelioid sarcoma with aggressive behavior, harboring an SS18::NEDD4 fusion.
Conformations of 4‐tert‐Butyloxy‐, 4‐(Trimethylsilyl)oxy‐ and 4‐(Trimethylstannyl)oxy‐6‐methyl‐2H‐pyran‐2‐ones in the Crystalline State and in Solution
Authors: Baak Marcel , Jaun Bernhard , Belaj Ferdinand , Neier Reinhard
Published: May 2022

The conformational studies in solution and in the solid state of substituted 6‐methyl‐4‐hydroxy‐2‐pyrones indicated that the substituents on the 4‐hydroxy group clearly favored the s‐cis arrangement towards the formal double bond. Steady state kinetic NOE measurements of the tert‐butyl, trimethylsilyl and the trimethylstannyl derivatives showed a marked preference for this conformation in solution. The structures determined by X‐ray diffraction demonstrated the exclusive presence of the same conformation in the solid state. In these three derivatives, the pertinent dihedral angle deviates only slightly from the value for coplanarity with the formal double bond. The predictions of the τ‐bond model are in accordance with the observations. The X‐ray structure of the trimethylstannyl derivative reveals pentacoordinated tin with short contacts to the oxygens at the 2 and 4 position of neighboring molecules. The tin center plays both the role of a protecting group for the 4‐hydroxy moiety and of a Lewis acid towards the 2‐carbonyl oxygen. The X‐ray structure of the stannyl derivative shows unique features which can be compared to the extended transition state of aldol reactions.
Carfilzomib combined with lenalidomide and dexamethasone (KRd) as salvage therapy for multiple myeloma patients: italian, multicenter, retrospective clinical experience with 600 cases outside of controlled clinical trials
Authors: Martino Enrica Antonia , Conticello Concetta , Zamagni Elena , Pavone Vincenzo , Palmieri Salvatore , Musso Maurizio , Tacchetti Paola , Mele Anna , Catalano Lucio , Vigna Ernesto , Bruzzese Antonella , Mendicino Francesco , Botta Cirino , Vincelli Iolanda Donatella , Farina Giuliana , Barone Marialucia , Cangialosi Clotilde , Mancuso Katia , Rizziello Ilaria , Rocchi Serena , Falcone Antonietta Pia , Mele Giuseppe , Reddiconto Giovanni , Garibaldi Bruno , Iaccino Enrico , Tripepi Giovanni , Gamberi Barbara , Di Raimondo Francesco , Musto Pellegrino , Neri Antonino , Cavo Michele , Morabito Fortunato , Gentile Massimo
Published: May 2022

In combination with lenalidomide and dexamethasone (KRd), Carfilzomib has been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) on ASPIRE trial. Efficacy and safety of the triplet are still the object of investigation by many groups to confirm ASPIRE results in the setting of RRMM treated in real‐life who don't meet trial restrictive inclusion criteria. Therefore, we report a retrospective multicenter analysis of 600 RRMM patients treated with KRd between December 2015 and December 2018. The median age was 64 years (range 33–85), and the median number of previous therapies was two (range 1–11). After a median of 11 KRd cycles, the overall response rate was 79.9%. The median progression‐free survival (PFS) was 22 months, and the 2‐year probability of PFS was 47.6%. Creatinine clearance<30 ml/min, >1 line of previous therapy, and high‐risk FISH were all associated with a poor prognosis in multivariate analysis. The median overall survival (OS) was 34.8 months; the 2‐year probability of OS was 63.5%. At multivariate analysis, creatinine clearance<30 ml/min, >1 line of previous therapy, and high‐risk FISH were significantly associated with poor prognosis. After a median follow‐up of 16 months (range 1–50), 259 withdrew from therapy. The main discontinuation reason was progressive disease (81.8%). Seventy‐four patients (12.3%) discontinued therapy for toxicity. The most frequent side effects were hematological (anemia 49.3%, neutropenia 42.7%, thrombocytopenia 42.5%) and cardiovascular (hypertension 14.5%, heart failure 2.5%, arrhythmias 3.6%). Our study confirms the safety and efficacy of KRd in the real‐life setting of RRMM patients and encourages its use in clinical practice.
Self‐Assembled Antimitotic Peptide Vesicle Designed fromα,β‐Tubulin Heterodimer Interface for Anticancer Drug Delivery
Authors: Mukherjee Nabanita , Roy Rajsekhar , Ghosh Satyajit , Ghosh Surajit
Published: May 2022

Peptide based anticancer molecule act simultaneously as potent anticancer therapeutic as well as unique drug delivery vehicle for the targeted delivery of often cytotoxic abysmally bioavailable anticancer drugs to their designated organelle. The atypical self‐assembling propensity of peptides gives rise to distinct nanostructures capable of encapsulating various drug payload. Among three different types of cytoskeletons presents in eukaryotes, microtubule plays a quintessential role during the course of cell cycle. Microtubule‐targeting agents continues to be the most unwavering classes of antineoplastic drugs for the treatment of cancer. Any intervention to the dynamic tubulin assembly‐disassembly process will definitely lead to complete perturbation of total cell division process. Several tubulin targeted antimitotic drugs had been designed as well as discovered to disrupt this dynamic nature of tubulin monomers either by inducing extensive polymerization or depolymerization, thereby facilitating overall cell cycle arrest. However, in cancer cells, aberrant mTOR activity causes growing resistance against numerous tubulin targeted drugs inducing metastasization, and simultaneous invasion to new healthy tissues. In recent years, numerous tubulin targeted drugs have been found to have high activity in a combination with mTOR inhibitors like tacrolimus, everolimus (RAD001) etc. but restrained bioavailability, non‐specificity and quick excretion are the major impediments for the successful implementation. Combining the immense importance of protein‐peptide interaction for the development of future anticancer therapeutics as well as self‐assembling propensity of peptides we have taken a unique approach to craft a microtubule targeting antimitotic peptide designed fromα,β‐tubulin heterodimer interface, which promotes bothin vitroandin vivotubulin depolymerization, exhibiting middling toxicity towards MCF7 cells, causing cell cycle arrest. Further AFM images of this β‐sheet forming peptide reveals that this peptide upon self‐assembly give rise to spectacular vesicle structural characteristics which can be used as a vehicle for a combination delivery of Docetaxel and RAD001 in order to enhance their individual therapeutic potency. Encapsulation of propidium iodide and concomitant release studies suggest that Pep‐4 vesicles could be a potential candidate for tubulin targeted sustained release of therapeutics. Here, our designed peptide vesicles are found to capable for the delivery of tubulin targeting drug Docetaxel along with an well‐known mTOR inhibiting drug RAD001 successfully to breast cancer cell line in order to achieve a robust symbiotic effect.
Microaggressions: Mega problems or micro issues? A meta‐analysis
Authors: Costa Paula L. , McDuffie Jessica W. , Brown Stephanie E. V. , He Yimin , Ikner Brittany N. , Sabat Isaac E. , Miner Kathi N.
Published: May 2022

While research on microaggressions has accumulated in recent decades, doubts have arisen over their impact on individuals. Hence, the purpose of this study was to analyze the relations between microaggressions and psychological well‐being, physical health, job outcomes, and positive and negative coping. Potential moderators (i.e., microaggression target, publication year, publication status, sample occupation, and inclusion of nonstigmatized group members) were also examined. A meta‐analytic approach was chosen to summarize the findings in the microaggression literature. Several search terms and databases were used to identify articles for inclusion. After review, a total of 141 articles with 154 samples contributed effect sizes to our analyses. The results showed that microaggressions were negatively related to psychological well‐being and physical health and positively related to coping. The pattern of results was generally the same regardless of the microaggression target, the year the study was conducted, the publication status of the paper, the occupation of the sample, and whether the sample included nonstigmatized groups members or not. This meta‐analysis demonstrates the stable, harmful effects associated with experiencing microaggressions. Specifically, microaggressions predicted negative outcomes across individuals and contexts. Thus, actions should be taken to decrease their prevalence within educational and occupational settings.
Lymphoma‐associated acquired von Willebrand syndrome responsive to splenectomy: A case report
Authors: Khadadah Fatima , Rupani Natasha , Scott Jordan , Trinkaus Martina , Teitel Jerome , Sholzberg Michelle
Published: May 2022

A previously healthy 33‐year‐old female presented with a large hematoma over her right knee after kneeling. She was found to have pancytopenia and massive splenomegaly. Von Willebrand Factor (VWF) antigen level was 0.38 units/ml, ristocetin cofactor activity 0.13 units/ml, and VWF multimeric distribution was normal. Bone marrow examination revealed an indolent B‐cell lymphoma. Diagnosis was consistent with acquired von Willebrand syndrome as an autoimmune epiphenomenon of a lymphoma. Diagnostic and therapeutic splenectomy under hemostatic coverage was performed. VWF antigen levels and activities immediately normalized postoperatively and remained within the normal range several months later. Splenic pathology confirmed hairy cell leukemia with a BRAF mutation.
Acteoside promotes B cell-derived IL-10 production and ameliorates autoimmunity
Authors: Wu Meiling , Yu Sulan , Chen Yacun , Meng Wei , Chen Haiyong , He Jing , Shen Jiangang , Lin Xiang
Published: May 2022

IL-10-producing regulatory B (Breg) cells are well recognized for maintaining immune tolerance. The impaired Breg cell function with decreased IL-10-producing capacity has been found in autoimmune diseases, such as rheumatoid arthritis, lupus, and primary Sjogren's syndrome (pSS). However, seldom therapeutic agents targeting Breg cells are available to treat those autoimmune diseases. Here, we showed that acteoside (AC), a caffeoyl phenylethanoid glycoside from a medicinal herb Radix Rehmanniae, could promote IL-10 production from both human and murine B cells via critically regulating the TLR4/PI3K axis. Moreover, TLR4 was found increased in Breg cells from mice with experimental SS (ESS), a mouse model that recapitulates human pSS. Thus, B cells from the ESS mice were susceptible to AC treatment, showing higher IL-10-producing capacity than those from naïve controls. In addition, AC treatment also promoted the production of IL-10 from TLR4+CXCR4+ plasma cells of ESS mice. Notably, we found that AC was able to enter lymphoid organs upon oral administration. AC treatment effectively increased IL-10+ B cells in ESS mice and ameliorated disease pathology accompanied by reduced T effector cells, including Th17 and T follicular helper cells in the ESS mice. In conclusion, AC could promote Breg cell function and attenuate ESS pathology in vivo, which may be a promising drug candidate for treating pSS and other autoimmune diseases.
Paradigms of actinorhizal symbiosis under the regime of global climatic changes: New insights and perspectives
Authors: Chetri Siva P. K. , Rahman Zeeshanur , Thomas Lebin , Lal Ratan , Gour Tripti , Agarwal Lokesh Kumar , Vashishtha Akanksha , Kumar Sachin , Kumar Gaurav , Kumar Rajesh , Sharma Kuldeep
Published: May 2022

Nitrogen occurs as inert and inaccessible dinitrogen gaseous form (N2) in the atmosphere. Biological nitrogen fixation is a chief process that makes this dinitrogen (N2) accessible and bioavailable in the form of ammonium (NH4+) ions. The key organisms to fix nitrogen are certain prokaryotes, called diazotrophs either in the free‐living form or establishing significant mutual relationships with a variety of plants. On such examples is ~95–100 MY old incomparable symbiosis between dicotyledonous trees and a unique actinobacterial diazotroph in diverse ecosystems. In this association, the root of the certain dicotyledonous tree (~25 genera and 225 species) belonging to three different taxonomic orders, Fagales, Cucurbitales, and Rosales (FaCuRo) known as actinorhizal trees can host a diazotroph, Frankia of order Frankiales. Frankia is gram‐positive, branched, filamentous, sporulating, and free‐living soil actinobacterium. It resides in the specialized, multilobed, and coralloid organs (lateral roots but without caps), the root nodules of actinorhizal tress. This review aims to provide systematic information on the distribution and the phylogenetic diversity of hosts from FaCuRo and their micro‐endosymbionts (Frankia spp.), colonization mechanisms, and signaling pathways. We also aim to provide details on developmental and physiological imperatives for gene regulation and functional genomics of symbiosis, phenomenal restoration ecology, influences of contemporary global climatic changes, and anthropogenic impacts on plant–Frankia interactions for the functioning of ecosystems and the biosphere.
Understanding the water structures by near‐infrared and Raman spectroscopy
Authors: Han Li , Sun Yan , Wang Shiying , Su Tao , Cai Wensheng , Shao Xueguang
Published: May 2022

The structure of water in different systems has been extensively studied due to the complexity and flexibility of the hydrogen‐bonded network and the important role in chemical and biological processes. Near‐infrared (NIR) and Raman spectroscopy has been used to investigate the structures of water and the interactions in aqueous systems. In this review, works for structural analysis of water by NIR and Raman spectroscopy were summarized. From resolution‐enhanced spectra, the spectral components of water were obtained. The spectral features correspond to the structures of water with different hydrogen bonds and the interactions of water and solutes. Following the concept of aquaphotomics, the changes of the spectral pattern of water with different perturbations, such as the variation of composition and temperature, were studied. The spectral pattern was found to be related to the analytes in the analyzing system and can be used to reflect the properties of the solutes and even disease diagnosis. Furthermore, water structures in the conformational change of macromolecules such as proteins and polymers were analyzed. Water was proved to be an indicator of the changes, and the water structures with two or three hydrogen bonds (S2 or S3) were found to have an important role in the phase transition of the proteins and polymers.
An integrated strategy to reveal the potential anti‐asthma mechanism of peimine by metabolite profiling, network pharmacology, and molecular docking
Authors: Tian Xi , Wei Jinhuan , Yang Mengxin , Niu Yukun , Liu Minyan , Du Yingfeng , Jin Yiran
Published: May 2022

Peimine, one of the major quality markers in Fritillaria Cirrhosae Bulbus, was expected to become a new anti‐asthma drug. However, its metabolic profiles and anti‐asthma mechanism have not been clarified previously. In this study, a method was developed for the detection of peimine metabolites in vitro by ultra‐high‐performance liquid chromatography coupled with hybrid triple quadrupole time‐of‐flight mass spectrometry. The potential anti‐asthma mechanism was predicted by an integrated analysis of network pharmacology and molecular docking. A total of 19 metabolites were identified with the aid of software and molecular networking. The metabolic profiles of peimine elucidated that the metabolism was a multi‐pathway process with characteristics of species difference. The network pharmacology results showed that peimine and its metabolites could regulate multiple asthma‐related targets. The above targets were involved in various regulatory pathways linked to asthma. Moreover, the results of molecular docking showed that both peimine and its metabolites had a certain affinity with the β2 adrenergic receptor. The results provided not only important references to understand the metabolism and pharmacodynamic changes of peimine in vitro, but also supporting data for further pharmacological evaluation. It also provided a new perspective for clarifying the functional changes of traditional Chinese medicine in vitro.
Quality of Life Measurement for Adolescent Patients with Sinonasal Symptoms
Authors: Makary Chadi A , Tumlin Parker , Asad Fatima , Wasef Kareem , Ramadan Hassan H
Published: May 2022

Objectives

To validate each of the sino‐nasal outcome test (SNOT‐22) and the sinus and nasal quality of life (SN5) surveys for the adolescent population defined as 12 to 18 years old, and to determine if they correlate in regard to reports of sinonasal symptoms and quality of life.

Study Design

Cross‐sectional study.

Methods

Adolescent patients, age 12 to 18 years old, presenting to our otolaryngology clinic between August 2020 and June 2021 were asked to fill both the SNOT‐22 and the SN5 forms. Demographics and comorbidities were reviewed. Patients recruited were then divided into a sinonasal cohort (those with chronic sinonasal symptoms) and a control cohort (those who did not have any sinonasal disorders at time of visit).

Results

One hundred fifteen patients completed both surveys, 80 patients in the sinonasal cohort and 35 patients in the control cohort. Average age was 14.9 years, and 49.6% were female. Mean SNOT‐22 and SN5 scores were significantly higher in the sinonasal cohort as compared with the control cohort which confirmed validity of both surveys for the adolescents. Good test–retest reliability for both surveys was obtained (r = 0.76 for SNOT‐22, and r = 0.64 for SN5). SNOT‐22 and SN5 scores correlated well in both the sinonasal cohort (r = 0.63, p < 0.0001) and the control cohort (r = 0.61, p = 0.0003). Both surveys strongly predicted chronic sinonasal disorders with an odds ratio of 2.5 for SNOT‐22 and 2.2 for SN5.

Conclusion

Both instruments can be used to study the outcome of treatment for sinonasal disorders in adolescent patients.

Level of Evidence

4 Laryngoscope, 133:1052–1058, 2023
Excavated farmland treated with plastic mulching as a strategy for groundwater conservation and the control of soil salinization
Authors: Ke Zengming , Liu Xiaoli , Ma Lihui , Dong Qin'ge , Jiao Feng , Wang Zhanli
Published: May 2022

Soil salinization and water deficits in gully consolidation farmland including excavated farmland (EF) and sediment deposited farmland (SF) have become an increasing concern in the Loess Hilly region, China. However, the responses of different farmland types and tillage‐mulching practices on soil salt content (SSC) and water use efficiency (WUE) have not been widely studied in this region. Thus, we conducted a two‐year field experiment to assess the soil water content (SWC) and SSC and their effect on the spring maize yield and WUE under different tillage‐mulching practices in EF and SF. Eight treatments incorporating flat cropping without mulching (FC), ridge planting without mulching (RP), ridge cropping with straw mulching (SM), and ridge cropping with plastic mulching (PM) were applied to EF and SF plots, respectively. Our results indicated that the yield of spring maize was limited by SWC (p < 0.01). Although EF had a low yield of spring maize compared to SF, it had the highest WUE (p < 0.01), which was mainly due to the lower groundwater consumption. Meanwhile, the average SSC was significantly lower in EF than in SF (p < 0.01). PM had the highest SWC (14.9%) and significantly reduced the accumulation of SSC (−0.09 g kg−1), thereby improving spring maize yield (12,200 kg ha−1) and WUE (1.71 kg m−3) (p < 0.05). These results suggested that EF with PM is optimal for groundwater conservation, decreasing the risk of soil salinization, and improving WUE and maize yield in dryland agricultural areas.
Plants, soil properties and microbes directly and positively drive ecosystem multifunctionality in a plantation chronosequence
Authors: Wang Jianqing , Shi Xiuzhen , Lucas‐Borja Manuel Esteban , Lam Shu Kee , Wang Zhenyu , Huang Zhiqun
Published: May 2022

Chinese fir (Cunninghamia lanceolata) is the main plantation species in the subtropical region of China. However, the shift in ecosystem multifunctionality with stand development remains largely unexplored for these plantations. This study used a chronosequence to investigate the variations of ecosystem multifunctionality by employing individual functions and identified its driving factors in Chinese fir plantations. The findings provide strong evidence that the individual functions of carbon stocks, water regulation and wood production increased with stand ages, but the tradeoff of individual functions did not significantly increase ecosystem multifunctionality. Soil microbial parameters (the abundances of bacteria, fungi and actinomycete), soil properties (soil moisture, total carbon and total nitrogen), and plant parameters (the shrub layer cover and total understory cover) exhibited positive correlations with ecosystem multifunctionality. The structural equation model revealed that plants, soil properties and microbes pathways explained 83% of the total variance in ecosystem multifunctionality. Results showed that plants, soil microbes and properties directly and significantly affected ecosystem multifunctionality with path coefficients of 0.404, 0.487 and 0.334, respectively. Soil microbes were identified as the top direct predictor for ecosystem multifunctionality, while plant and soil properties had strong direct and positive effects on ecosystem multifunctionality. These results verified that soil microbes, plants and soil properties directly and positively regulated ecosystem multifunctionality. Our findings demonstrate that ecosystem multifunctionality should be considered as a comprehensive ecological indicator for ecosystem services and functions, and sustainable plantation management. This study highlights the importance of conserving soil microbes for maintaining multifunctionality in Chinese fir plantations.
Synthesis of High‐Molecular‐Weight and Strength Polyisobutylene‐Based Polyurethane and Its Use for the Development of a Synthetic Heart Valve
Authors: Deodhar Tejal , Nugay Nihan , Nugay Turgut , Patel Ruhi , Moggridge Geoff , Kennedy Joseph Paul
Published: May 2022

Under optimized synthesis conditions, for the first time, polyisobutylene‐based polyurethane (PIB–PU) is prepared with 70% PIB soft segment (i.e., a bioinert and calcification‐resistant PU) with Mn > 100 000 Da, 32 MPa ultimate strength, and 630% elongation. The key parameters for this achievement are a) the precise stoichiometry of the polyurethane forming reaction, specifically the use of highly purified di‐isocyanate (4,4′‐methylene‐bis (phenyl isocyanate), MDI), and b) the increased solid content of the synthesis solution to the limit beyond which increased viscosity prevents stirring. The shape of the stress–strain trace of PIB–PU indicates a two‐step failure starting with a reversible elastic (Hookean) region up to ≈50% yield, followed by a slower linearly increasing high‐modulus‐deformation region suggesting the strengthening of PIB soft segments by entanglement/catenation, and the hard segments by progressively ordering urethane domains. This PIB–PU is a candidate for a fully synthetic bioprosthetic heart valve since preliminary studies show that PIB–PU has impressive fatigue life.
CAF‐derived exosomes transmitted Gremlin‐1 promotes cancer progression and decreases the sensitivity of hepatoma cells to sorafenib
Authors: Qin Wei , Wang Li , Tian Huan , Wu Xiaocai , Xiao Cuicui , Pan Yuhang , Fan Mingming , Tai Yan , Liu Wei , Zhang Qi , Yang Yang
Published: May 2022

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide because of metastasis. An increasing number of studies have reported that cancer‐associated fibroblasts (CAFs) have emerged as the largest component of the stroma and play a critical role in tumor‐promoting processes. However, the effects of CAFs on cancer progression and the sensitivity of hepatoma cells to sorafenib are not well characterized. Here, we identified the proteome of CAF‐derived exosomes, and unveiled that exosomal Gremlin‐1 derived from CAFs contributes to epithelial–mesenchymal transition (EMT) of hepatoma cells and the decrease of the sorafenib sensitivity through regulating Wnt/β‐catenin and BMP signaling pathways. Compared to control subjects, the level of plasma exosomal Gremlin‐1 was significantly increased in HCC patients. Further studies indicated that plasma exosomal Gremlin‐1 may predict sorafenib response in HCC patients. Collectively, our findings uncover CAFs‐derived Gremlin‐1‐rich exosomes promote EMT and decrease the sensitivity of hepatoma cells to sorafenib by Wnt/β‐catenin and BMP signaling.
Influence of flow and susceptibility effects on spin dephasing in lung tissue
Authors: Rotkopf Lukas T. , Kampf Thomas , Triphan Simon M. F. , Schlemmer Heinz‐Peter , Ziener Christian H.
Published: May 2022

Purpose

Magnetic resonance imaging (MRI) of the lung can be used for diagnosis and monitoring of interstitial lung disease. Biophysical models of alveolar lung tissue are needed to understand the complex interplay of susceptibility, diffusion, and flow effects, and their influence on magnetic resonance (MR) spin dephasing.

Methods

In this work, we present a method for modeling the signal decay of lung tissue by utilizing a two‐compartment model, which considers the different spin dephasing mechanisms in the alveolar vasculature and interstitial tissue. This allows calculating the magnetization dynamics and the MR lineshape, which can be measured noninvasively using clinical MR scanners.

Results

The accuracy of the method was evaluated using finite element simulations and the experimentally measured lineshapes of a healthy volunteer. In this comparison, the model performs well, indicating that the relevant spin dephasing mechanisms are correctly taken into account.

Conclusions

The proposed method can be used to estimate the influence of blood flow and alveolar geometry on the MR lineshape of lung tissue.
Risikobewertung: Sortieren, vergleichen, gruppieren
Authors: Klemeyer Horst
Published: May 2022

Das Stoffgruppenkonzept der europäischen Chemikalienagentur stuft Stoffe und Gemische ein, bei denen toxikologische Prüfdaten fehlen. Mit einem systematischen Datenabgleich lassen sich die Gefahren realistisch einschätzen.
Local delivery of tumor‐targeting nano‐micelles harboring GSH‐responsive drug release to improve antitumor efficiency
Authors: Li Xiaoqiang , Shi Yongli , Xu Shuxin
Published: May 2022

Increasing the accumulation of therapeutics in tumor site and improving the bioavailability of delivered drug are vital strategies to enhance chemotherapy efficiency as well as reduce side effects. Herein, we report an injectable hydrogel system to locally deliver tumor‐targeting nano‐micelles with GSH‐responsive drug release to improve antitumor efficiency. Amphiphilic polymers with different functions were designed and successfully synthesized. Then, the prepared polymers self‐assembled into nano‐micelles (PPR‐NP), which exhibited tumor cell targeting and GSH‐responsive drug release behavior. Furthermore, we constructed an injectable hydrogel system composed of the nano‐micelles (PPR‐NP@α‐CDgel). Peritumorally administrated to tumor site, PPR‐NP@α‐CDgel sustainedly released PPR‐NP around tumor site in situ, which were specifically taken up by tumor cells and rapidly released loaded paclitaxel in responsible to the high concentration of GSH in tumor cell, thus effectively inhibiting tumor growth. Synergized by the multitargeting effect, the present system could effectively improve the bioavailability of antineoplastic drug and enhance the antitumor efficiency, holding potential for solid tumor therapy.
Development of highly alkaline stable anion conductive polymers with fluorene backbone for water electrolysis
Authors: Nara Yuri , Tanaka Manabu , Nagasawa Kensaku , Kuroda Yoshiyuki , Mitsushima Shigenori , Kawakami Hiroyoshi
Published: May 2022

Anion exchange membrane water electrolysis (AEMWE) is currently paying attention as a new hydrogen (H2) production method since it can operate at high current densities using inexpensive nonnoble metal catalysts. However, the significant problems of AEMs, including their insufficient anion conductivity and alkaline stability, prevent the practical usage of AEMWE. We show a novel anion conductive polymer, alkyl trimethylammonium‐substituted polyfluorene (TMA‐PF), bearing no heteroatom bonds in the main chain. The TMA‐PF membrane possesses higher anion conductivity than conventional AEMs due to the increased flexibility and mobility of the alkylammonium side chains of TMA‐PF. The TMA‐PF membrane shows high‐alkaline stability and maintains the initial ion conductivity after immersion in an aqueous NaOH solution (8 mol L−1) at 80°C for 48 h. In the water electrolysis evaluation, the cell using the TMA‐PF membrane exhibits a higher current density (400 mA cm−2 at 2.03 V) than the cell using the conventional AEM at the same potential, indicating that the novel AEM has a high potential to generate H2 effectively. Green hydrogen produced by AEMWE using renewable energy will be an environmentally benign energy source without CO2 emissions.
Sarcopenic obesity in liver disease: Handling both sides of the penny
Authors: Hui Yangyang , Cui Binxin , Wang Xiaoyu , Sun Mingyu , Li Yifan , Yang Wanting , Guo Gaoyue , Mao Lihong , Yu Zihan , Fan Xiaofei , Sun Chao
Published: May 2022

Skeletal muscle and fat tissue show distinct pathophysiological roles and pivotal functions. The culmination of muscle wasting and fat accumulation represents an opposite terminal of each state. Specifically, this situation has been designated as sarcopenic obesity. However, sarcopenic obesity still lacks a unanimous definition, diagnostic criteria, and generalized modalities for assessment in the context of versatile liver diseases. Moreover, the underpinning mechanisms by which a combination of abnormal skeletal muscle and fat tissue leads to the progression of liver disease and impairs health‐related consequences are still elusive. Additionally, the interplay between skeletal muscle and fat, and the driving factors that shift different body compositions are not well understood. Therefore, in this review, we discuss skeletal muscle and fat components, with the purpose of conceptualization, as well as interpret their roles in liver diseases. We focus on the definitions, diagnostic criteria, and currently available measurements for sarcopenic obesity in the literature. We comprehensively discuss recent data and evidence regarding the potential role of sarcopenic obesity in the development and progression of numerous liver diseases and associated conditions, including nonalcoholic fatty liver disease, chronic viral hepatitis, cirrhosis, and liver transplantation. Furthermore, explicit information related to the pathogenesis of sarcopenic obesity from basic research is also provided in this narrative review. Finally, we discuss, from the clinical perspective of view, how to manage sarcopenic obesity using nutritional, physical, and pharmacological methods.
State welfare automation, Working‐Class Agency, and Poverty in I, Daniel Blake
Authors: Furlan Brighente Miriam
Published: May 2022

In this review essay, I examined I, Daniel Blake, a film directed by Loach that depicts Daniel's life, a 59‐year‐old widowed woodworker, who had a heart attack and was unable to work, and the dehumanizing process he experiences when applying to receive government benefits in the United Kingdom. The movie shows how poor and working‐class people struggle to receive state assistance, to have at least something to eat and a place to live. Sadly, applicants often fail or give up midway because the welfare automation system is entirely online, and applicants often do not understand the jargon used by state employees, much less the questions on the application forms. Despite constraints, such as backlashes from the middle class, economic elite, and conservative politicians, the ill, single mothers, and Black people—usually the groups most affected by the welfare automation system—exercise their agency to survive the material and symbolic hardships of poverty, as seen in the scenes of the movie.
Impaired exercise outcomes with significant bronchodilator responsiveness in children with prematurity‐associated obstructive lung disease
Authors: Cousins Michael , Hart Kylie , Williams E. Mark , Kotecha Sailesh
Published: May 2022

Introduction

Preterm‐born children have their normal in‐utero lung development interrupted, thus are at risk of short‐ and long‐term lung disease. Spirometry and exercise capacity impairments have been regularly reported in preterm‐born children especially those who developed chronic lung disease of prematurity (CLD) in infancy. However, specific phenotypes may be differentially associated with exercise capacity. We investigated exercise capacity associated with prematurity‐associated obstructive (POLD) or prematurity‐associated preserved ratio of impaired spirometry (pPRISm) when compared to preterm‐ and term‐controls with normal lung function.

Materials and Methods

Preterm‐ and term‐born children identified through home screening underwent in‐depth lung function and cardiorespiratory exercise testing, including administration of postexercise bronchodilator, as part of the Respiratory Health Outcomes in Neonates (RHiNO) study.

Results

From 241 invited children, aged 7–12 years, 202 underwent exercise testing including 18 children with POLD (percent predicted (%)FEV1 and FEV1/FVC < LLN); 12 pPRISm (%FEV1 < LLN and FEV1/FVC ≥ LLN), 106 preterm‐controls (PTc, %FEV1 ≥ LLN) and 66 term‐controls (Tc, %FEV1 > 90%). POLD children had reduced relative workload, peak O2 uptake, CO2 production, and minute ventilation compared to Tc, and used a greater proportion of their breathing reserve compared to both control groups. pPRISm and PTc children also had lower O2 uptake compared to Tc. POLD children had the greatest response to postexercise bronchodilator, improving their %FEV1 by 19.4% (vs 6.3%, 6% 6.3% in pPRISm PTc,Tc, respectively; p < .001).

Conclusion

Preterm‐born children with obstructive airway disease had the greatest impairment in exercise capacity, and significantly greater response to postexercise bronchodilators. These classifications can be used to guide treatment in children with POLD.
Introducing HyPeak: An international network on hydropeaking research, practice, and policy
Authors: Alp Maria , Batalla Ramon J. , Bejarano Maria Dolores , Boavida Isabel , Capra Hervé , Carolli Mauro , Casas‐Mulet Roser , Costa Maria João , Halleraker Jo Halvard , Hauer Christoph , Hayes Daniel S. , Harby Atle , Noack Markus , Palau Antoni , Schneider Matthias , Schönfelder Lennart , Tonolla Diego , Vanzo Davide , Venus Terese , Vericat Damià , Zolezzi Guido , Bruno Maria Cristina
Published: May 2022

An increase in the demand for renewable energy is driving hydropower development and its integration with variable renewable energy sources. When hydropower is produced flexibly from hydropower plants, it causes rapid and frequent artificial flow fluctuations in rivers, a phenomenon known as hydropeaking. Hydropeaking and associated hydrological alterations cause multiple impacts on riverine habitats with cascading effects on ecosystem functioning and structure. Given the significance of its ecological and socio‐economic implications, mitigation of hydropeaking requires an inter‐ and transdisciplinary approach. An interdisciplinary network called HyPeak has been conceived to enrich international research initiatives and support hydropower planning and policy. HyPeak has been founded based on exchange and networking activities linking scientists from several countries where hydropeaking has been widespread for decades and numerous studies dedicated to the topic have been carried out. HyPeak aims to integrate members from other countries and continents in which hydropower production plays a relevant role, and grow to be a reference group that provides expert advice on the topic to policy‐makers, as well as researchers, stakeholders, and practitioners in the field of hydropeaking.