bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between exposures to radon and γ‐ray radiation and histologic type of lung cancer in Eldorado uranium mining and milling workers from Canada
Authors: Zablotska Lydia B. , Lane Rachel S. D. , Randhawa Kristi
Published: June 2022

Background

The authors assessed the association between radon decay products (RDP) exposure and histologic types of incident lung cancer in a cohort of 16,752 (91.6% male) Eldorado uranium workers who were first employed from 1932 to 1980 and were followed through 1969–1999.

Methods

Substantially revised identifying information and RDP exposures were obtained on workers from the Port Radium and Beaverlodge uranium mines and from the Port Hope radium and uranium refinery and processing facility in Canada. Poisson regression was conducted using the National Research Council's Biological Effects of Ionizing Radiation (BEIR) VI–type models to estimate the risks of lung cancer by histologic type from RDP exposures and γ‐ray doses.

Results

Lung cancer incidence was significantly higher in workers compared with the general Canadian male population. Radiation risks of lung cancer for all histologic types (n = 594; 34% squamous cell, 16% small cell, 17% adenocarcinoma) increased with increasing RDP exposure, with no indication of curvature in the dose response (excess relative risk per 100 working level months = 0.61; 95% confidence interval, 0.39–0.91). Radiation risks did not differ by histologic type (p = .144). The best‐fitting BEIR VI–type model included adjustments for the significant modifying effects of time since exposure, exposure rate, and attained age. The addition of γ‐ray doses to the model with RDP exposures improved the model fit, but the risk estimates remained unchanged.

Conclusions

The first analysis of radiation risks of lung cancer histologic types in the Eldorado cohort supported the use of BEIR VI–type models to predict the future risk of histologic types of lung cancer from past and current RDP exposures.

Lay summary

Lung cancer survival depends strongly on the cell type of lung cancer.

The best survival rates are for patients who have the adenocarcinoma type.

This study included 16,752 Eldorado uranium workers who were exposed to radon and γ‐ray radiation during 1932–1980, were alive in 1969, and were followed for the development of new lung cancer during 1969–1999.

One third of all lung cancers were of the squamous cell type, whereas the adenocarcinoma and small cell types accounted for less than 20% each.

Radiation risks of lung cancer among men increased significantly with increasing radon exposure for all cell types, with the highest risks estimated for small cell and squamous cell lung cancers.
The brain of the tree pangolin (Manis tricuspis). X. The spinal cord
Authors: Imam Aminu , Bhagwandin Adhil , Ajao Moyosore S. , Manger Paul R.
Published: June 2022

The spinal cord of the tree pangolin is known to be very short compared to the overall length of the body and tail. Here, we provide a description of the tree pangolin spinal cord to determine whether the short length contributes to specific structural, and potentially functional, differences. The short spinal cord of the adult tree pangolin, at around 13 cm, terminates at the midthoracic level. Within this shortened spinal cord, we could identify six regions, which from rostral to caudal include the prebrachial, brachial, interramal, crural, postcrural, and caudal regions, with both the brachial and crural regions showing distinct swellings. The chemoarchitecture of coronal sections through these regions confirmed regional assignation, being most readily delineated by the presence of cholinergic neurons forming the intermediolateral column in the interramal region and the sacral parasympathetic nucleus in the postcrural region. The 10 laminae of Rexed were observed throughout the spinal cord and presented with an anatomical organization similar to that observed in other mammals. Despite the shortened length of the tree pangolin spinal cord, the regional and laminar anatomical organization is very similar to that observed in other mammals. This indicates that the functional aspects of the short tree pangolin spinal cord can be inferred from what is known in other mammals.
Development of a Translational Model to Assess the Impact of Opioid Overdose and Naloxone Dosing on Respiratory Depression and Cardiac Arrest
Authors: Mann John , Samieegohar Mohammadreza , Chaturbedi Anik , Zirkle Joel , Han Xiaomei , Ahmadi S. Farzad , Eshleman Amy , Janowsky Aaron , Wolfrum Katherine , Swanson Tracy , Bloom Shelley , Dahan Albert , Olofsen Erik , Florian Jeffry , Strauss David G. , Li Zhihua
Published: June 2022

In response to a surge of deaths from synthetic opioid overdoses, there have been increased efforts to distribute naloxone products in community settings. Prior research has assessed the effectiveness of naloxone in the hospital setting; however, it is challenging to assess naloxone dosing regimens in the community/first‐responder setting, including reversal of respiratory depression effects of fentanyl and its derivatives (fentanyls). Here, we describe the development and validation of a mechanistic model that combines opioid mu receptor binding kinetics, opioid agonist and antagonist pharmacokinetics, and human respiratory and circulatory physiology, to evaluate naloxone dosing to reverse respiratory depression. Validation supports our model, which can quantitatively predict displacement of opioids by naloxone from opioid mu receptors in vitro, hypoxia‐induced cardiac arrest in vivo, and opioid‐induced respiratory depression in humans from different fentanyls. After validation, overdose simulations were performed with fentanyl and carfentanil followed by administration of different intramuscular naloxone products. Carfentanil induced more cardiac arrest events and was more difficult to reverse than fentanyl. Opioid receptor binding data indicated that carfentanil has substantially slower dissociation kinetics from the opioid receptor compared with nine other fentanyls tested, which likely contributes to the difficulty in reversing carfentanil. Administration of the same dose of naloxone intramuscularly from two different naloxone products with different formulations resulted in differences in the number of virtual patients experiencing cardiac arrest. This work provides a robust framework to evaluate dosing regimens of opioid receptor antagonists to reverse opioid‐induced respiratory depression, including those caused by newly emerging synthetic opioids.
Two Novel Dinuclear Cobalt Polypyridyl Complexes in Electro‐ and Photocatalysis for Hydrogen Production: Cooperativity Increases Performance
Authors: Weder Nicola , Grundmann Nora S. , Probst Benjamin , Blacque Olivier , Ketkaew Rangsiman , Creazzo Fabrizio , Luber Sandra , Alberto Roger
Published: June 2022

Syntheses and mechanisms of two dinuclear Co‐polypyridyl catalysts for the H2 evolution reaction (HER) were reported and compared to their mononuclear analogue (R1). In both catalysts, two di‐(2,2’‐bipyridin‐6‐yl)‐methanone units were linked by either 2,2’‐bipyridin‐6,6’‐yl or pyrazin‐2,5‐yl. Complexation with CoII gave dinuclear compounds bridged by pyrazine (C2) or bipyridine (C1). Photocatalytic HER gave turnover numbers (TONs) of up to 20000 (C2) and 7000 (C1) in water. Electrochemically, C1 was similar to the R1, whereas C2 showed electronic coupling between the two Co centers. The E(CoII/I) split by 360 mV into two separate waves. Proton reduction in DMF was investigated for R1 with [HNEt3](BF4) by simulation, foot of the wave analysis, and linear sweep voltammetry (LSV) with in‐line detection of H2. All methods agreed well with an (E)ECEC mechanism and the first protonation being rate limiting (≈104 m−1 s−1). The second reduction was more anodic than the first one. pKa values of around 10 and 7.5 were found for the two protonations. LSV analysis with H2 detection for all catalysts and acids with different pKa values [HBF4, pKa(DMF)≈3.4], intermediate {[HNEt3](BF4), pKa(DMF)≈9.2} to weak [AcOH, pKa(DMF)≈13.5] confirmed electrochemical H2 production, distinctly dependent on the pKa values. Only HBF4 protonated CoI intermediates. The two metals in the dualcore C2 cooperated with an increase in rate to a competitive 105 m−1 s−1 with [HNEt3](BF4). The overpotential decreased compared to R1 by 100 mV. Chronoamperometry established high stabilities for all catalysts with TONlim of 100 for R1 and 320 for C1 and C2.
A novel multi‐hop routing structure for throughput maximization in unmanned aerial vehicle assisted flying ad‐hoc networks
Authors: Mittal Payal , Shah Santosh , Agarwal Anirudh
Published: June 2022

Unmanned aerial vehicle (UAV) aided wireless communication has many potential uses to improve connectivity in the harsh environments due to its high mobility and flexible deployment. To extend the coverage, multi‐hop communication with multiple UAVs as relays has become the prominent scheme in today's wireless network. In this article, we investigate the problem of generating a multi‐hop routing structure for data transmission to maximize the overall network throughput of a flying ad‐hoc network using UAVs. Specifically, we propose an optimization problem to jointly select a communication link and its transmission power so that the overall network throughput for a given total power budget is maximized. The problem is nonconvex over selected metrics, thus making it an NP‐hard problem. Without loss of generality, we consider the Dijkstra‐based shortest‐path tree as a routing structure, thereby converting the original problem into a solvable convex problem over the transmission link metric. We observe Dijkstra‐based routing is not optimal in our scenario, thus we propose a low complexity link swap approach to further improve the network throughput by exchanging appropriate child‐parent links of UAVs. Results are numerically validated, and optimal design insights are provided.
Margin requirements based on a stochastic correlation model
Authors: Szabó Dávid Zoltán , Váradi Kata
Published: June 2022

We demonstrate that margin requirements of central counterparties show a significantly different behavior when calculated with a portfoliowise treatment instead of taking the weighted sum of the margin requirements of the components without accounting for their correlation structures. This is shown via simulating trajectories of a joint stochastic volatility–stochastic correlation model. Results indicate that an unnecessarily large overmargin requirement is set by regulators when the applied risk measure is not calculated via a portfoliowise treatment. Finally, accounting for the correlation structure of the assets during the margining process would not lead to an overly prudent method, nor would it cause greater procyclicality.
Managing the delivery of venous leg ulcer services: A willingness to pay study
Authors: Wickramasekera Nyantara , Palfreyman Simon , Lumley Elizabeth , Dosanjh Arvind , Shackley Phil
Published: June 2022

Background and Aims

There is widespread variation in venous leg ulcer (VLU) wound care contributing to inadequate service provision resulting in poor outcomes to patients. Little has been published on the perspectives of where treatments should be carried out. The aim of the study was to quantify respondents' preferences for the preferred place of treatment for VLU.

Methods

A UK general population sample was interviewed to elicit preferences for clinic or home care treatment using the willingness to pay elicitation method. Participants were presented with two vignettes describing clinic or home care of VLU, and were asked to select the treatment process that they preferred and provide a detailed explanation for selecting that choice. Then they were asked to state their maximum hypothetical amounts that they were willing to pay for the treatment processes.

Results

One hundred fifty‐four participants completed the interviews. Respondents were willing to pay £498.96 to receive VLU treatment at a clinic and £505.60 to receive care at home. This difference between the clinic compared to home care was not statistically significant. Advantages of clinic care include being able to book an appointment allowing participants to plan events around the booking and for home care the convenience for those with impaired mobility who may have difficulty traveling.

Conclusions

The results show that respondents placed an equal valuation on the place of treatment suggesting no strong preference for either home or clinic care. However, qualitative findings emphasized that impaired mobility may be a barrier to accessing VLU services for some therefore, individuals should be given the choice to select their preferred setting to receive treatment where possible.
Experimenter identity: An invisible, lurking variable in developmental research
Authors: St. Pierre Thomas , White Katherine S. , Johnson Elizabeth K.
Published: June 2022

Developmental researchers are well aware that children behave differently around different people. Nevertheless, researchers rarely consider (and report on) who is running their studies. Indeed, in a survey of articles published in the last 3 years in 4 top developmental journals, we find that the vast majority of studies fail to report any information about experimenter identity, despite the fact that child–adult interactions may be strongly influenced by the social inferences that individuals draw from one another. We argue that developmental researchers need to acknowledge how experimenter identity could be acting as an invisible, lurking variable, influencing the outcome and generalizability of studies. We provide simple suggestions for how researchers and journals can begin to address this issue, thereby improving the quality and depth of the work in our field.
Gallium‐based liquid metals for lithium‐ion batteries
Authors: Zhang Bin‐Wei , Ren Long , Wang Yun‐Xiao , Xu Xun , Du Yi , Dou Shi‐Xue
Published: June 2022

Lithium‐ion batteries (LIBs) are one of the most exciting inventions of the 20th century and have been widely employed in modern society. LIBs have powered many of our electronics, such as laptop computers, smartphones, and even large‐scale energy storage systems. With the development of modern technology, next‐generation LIBs with higher energy density are in demand. A number of electrode materials with high theoretical capacity, including Sn, Si, Li metal anode, and S cathode materials, have been explored. Nevertheless, they usually suffer from structural or interface failure during cycling, limiting their practical application. Ga‐based liquid metals (LMs) possess self‐healing capability, fluidity, and metallic advantages so they have been employed as self‐healing skeletons or interfacial protective layers to minimize the negative impact of volume expansion or dendritic growth on the electrode materials. Herein, the features of Ga‐based LMs are briefly discussed to indicate their potential for battery systems. In addition, recent developments on Ga‐based LMs applied in LIBs have been summarized, including from the aspects of anodes, cathodes, and electrolytes. Finally, future opportunities and challenges for the development of Ga‐based LMs in LIBs are highlighted.
The role of interpersonal trust and romantic experiences in mate copying
Authors: Zhou Tianshuang , Feng Caihua , Cui Lijuan
Published: June 2022

Mate copying occurs when individuals imitate the mate choice of other same‐sex individuals. These effects can be influenced by factors related to the rater and the model. The present study explored the roles of raters' interpersonal trust and models' romantic experiences in the decision‐making progress. Study 1 replicated mate copying effects and found the effect of interpersonal trust was nonsignificant. Study 2 further tested the interaction effect among interpersonal trust, model's romantic experiences, and model's mate choice decision. Results showed that change in targets' attractiveness varied with the model's romantic experiences under the model acceptance condition. The attractiveness of targets showed a greater increase when models had one or two romantic experiences than when they had no or multiple romantic experiences. A three‐way interaction effect occurred as well. Under the condition of model acceptance, for raters with a low or medium level of interpersonal trust, change in attractiveness increased with the model's romantic experiences and the relationship was non‐monotonic. For individuals with high levels of trust, models' romantic experiences did not have any effect. These results reveal that both rater's interpersonal trust and models' romantic experiences matter in individuals' willingness to copy other's mate preference.
Paracrine effect of the stromal vascular fraction containing M2 macrophages on human chondrocytes through the Smad2/3 signaling pathway
Authors: Fujita Masahiro , Matsumoto Tomoyuki , Hayashi Shinya , Hashimoto Shingo , Nakano Naoki , Maeda Toshihisa , Kuroda Yuichi , Takashima Yoshinori , Kikuchi Kenichi , Anjiki Kensuke , Ikuta Kemmei , Onoi Yuma , Tachibana Shotaro , Matsushita Takehiko , Iwaguro Hideki , Sobajima Satoshi , Hiranaka Takafumi , Kuroda Ryosuke
Published: June 2022

The adipose‐derived stromal vascular fraction (SVF) is composed of a heterogeneous mix of adipose‐derived stem cells (ADSCs), macrophages, pericytes, fibroblasts, blood, and other cells. Previous studies have found that the paracrine effects of SVF cells may be therapeutic, but their role in osteoarthritis treatment remains unclear. This study aimed to investigate the therapeutic effect of SVF cells on chondrocytes. Chondrocytes were seeded on culture plates alone (control) or cocultured with SVF or ADSCs on cell culture inserts. After 48 h of coculture, chondrocyte collagen II, tissue inhibitors of metalloproteinases‐3 (TIMP‐3), and matrix metalloproteinases‐13 (MMP‐13) messenger RNA (mRNA) expression levels were evaluated using reverse‐transcription polymerase chain reaction, and the transforming growth factor‐β (TGF‐β) levels in the supernatant were measured using ELISA. Immunohistochemical staining and flow cytometry were used to evaluate the macrophages in the SVF. These macrophages were characterized according to phenotype using the F4/80, CD86, and CD163 markers. To determine whether the Smad2/3 signaling pathways were involved, the chondrocytes were pre‑treated with a Smad2/3 phosphorylation inhibitor and stimulated with the SVF, and then Smad2/3 phosphorylation levels were analyzed using western blot. The mRNA expression levels of various paracrine factors and chondrocyte pellet size were also assessed. Collagen II and TIMP‐3 expression were higher in the SVF group than in the ADSC group and controls, while MMP‐13 expression was the highest in the ADSC group and the lowest in the controls. TGF‐β levels in the SVF group were also elevated. Immunohistochemical staining and flow cytometry revealed that the macrophages in the SVF were of the anti‐inflammatory phenotype. Western blot analysis showed that the SVF increased Smad2/3 phosphorylation, while Smad2/3 inhibitors decreased phosphorylation. Smad2/3 inhibitors also reduced the expression of various other paracrine factors and decreased chondrocyte pellet size. These findings suggested that the paracrine effect of heterogeneous cells, such as anti‐inflammatory macrophages, in the SVF partly supports chondrocyte regeneration through TGF‐β‐induced Smad2/3 phosphorylation.
Could melatonin have a potential adjuvant role in the treatment of the lasting anosmia associated with COVID‐19? A review
Authors: Xerfan Ellen M. S. , Morelhao Priscila K. , Arakaki Felipe H. , Facina Anamaria da Silva , Tomimori Jane , Xavier Sandra D. , Tufik Sergio , Andersen Monica L.
Published: June 2022

Introduction

Anosmia, the loss of the sense of smell, is usually associated with rhinopathies and has been reported as a common symptom of COVID‐19. There is no specific drug to treat this condition, although some evidence suggests that melatonin could promote the recovery of olfactory sensory neurons.

Methods

We set out to perform a narrative review to synthesize the current evidence in this area in respect of our hypothesis that melatonin may be linked with anosmia and play a part in oxidative stress and the regulation of inflammation. The main electronic databases (MEDLINE/PubMed, Embase, and Cochrane) were searched.

Results

The search produced 26 articles related to our hypothesis. Some studies examined issues related to melatonin's effects and its use as adjuvant therapy for COVID‐19. Despite some studies suggesting that melatonin may have potential in the treatment of COVID‐19, to the best of our knowledge, there have been no trials that have used it to treat anosmia associated with the disease. Few articles identified proposed that melatonin might have an effect on olfactory cells.

Discussion

Further experimental and clinical research on the role of circadian melatonin in the olfactory system is warranted. This will provide evidence of the use of melatonin in the management of anosmia. A number of identified studies suggest that the imbalanced release of melatonin by the pineal gland associated with sleep disturbance may play a role in anosmia, although the specific pathway is not yet entirely clear. This may be a base for further research into the potential role of melatonin as adjuvant treatment of anosmia.
Molecular and clinicopathological analysis of three cases of gastric juvenile polyposis
Authors: Yamashiro Yuya , Yanai Yuka , Takeda Tsutomu , Hayashi Takuo , Akazawa Yoichi , Yatagai Noboru , Ueyama Hiroya , Eguchi Hidetaka , Nagahara Akihito , Yao Takashi , Saito Tsuyoshi
Published: June 2022

Background and Aim

Juvenile polyposis (JP) is a rare disease known to be associated with mutations either in SMAD4/BMPR1A. JP is known to often develop into malignant tumors, with a reported probability of 9–50%. However, the mechanisms of its carcinogenesis are not fully understood. We tried to elucidate the mechanisms of malignant transformation underlying this condition in three cases of gastric JP.

Methods

We selected polyps from each patient displaying varying degrees of atypia and their nearby normal polyps and compared them using immunohistochemistry, Sanger sequencing, and loss of heterozygosity (LOH) analysis of SMAD4, BMPR1A, and TP53.

Results

Two of the three cases were suspected of having germline SMAD4 mutations based on their familial medical histories; the remaining case was found to have a SMAD4 germline mutation following preoperative genetic testing. All three cases were shown to present with both SMAD4 positive and negative areas across each lesion, with the neoplastic lesions tending to show stronger nuclear SMAD4 expression. This expression was closely associated with the SMAD4 LOH status; however, we also noted paradoxical SMAD4 expression in the neoplastic lesions despite the biallelic inactivation of SMAD4 revealed in the genetic evaluation.

Conclusions

These data suggest that strong nuclear expression of SMAD4, even when seemingly paradoxical, seems to be closely associated with dysplastic polyps in JP. Complete inactivation of SMAD4 was not shown to be essential for the development of dysplastic polyps in gastric JP, and other pathways seemed to be involved in the acquisition of the malignant phenotype.
SARS‐CoV‐2 ORF10 antagonizes STING‐dependent interferon activation and autophagy
Authors: Han Lulu , Zheng Yi , Deng Jian , Nan Mei‐Ling , Xiao Yang , Zhuang Meng‐Wei , Zhang Jing , Wang Wei , Gao Chengjiang , Wang Pei‐Hui
Published: June 2022

A characteristic feature of COVID‐19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, is the dysregulated immune response with impaired type I and III interferon (IFN) expression and an overwhelming inflammatory cytokine storm. RIG‐I‐like receptors (RLRs) and cGAS–STING signaling pathways are responsible for sensing viral infection and inducing IFN production to combat invading viruses. Multiple proteins of SARS‐CoV‐2 have been reported to modulate the RLR signaling pathways to achieve immune evasion. Although SARS‐CoV‐2 infection also activates the cGAS–STING signaling by stimulating micronuclei formation during the process of syncytia, whether SARS‐CoV‐2 modulates the cGAS–STING pathway requires further investigation. Here, we screened 29 SARS‐CoV‐2‐encoded viral proteins to explore the viral proteins that affect the cGAS–STING signaling pathway and found that SARS‐CoV‐2 open reading frame 10 (ORF10) targets STING to antagonize IFN activation. Overexpression of ORF10 inhibits cGAS–STING‐induced interferon regulatory factor 3 phosphorylation, translocation, and subsequent IFN induction. Mechanistically, ORF10 interacts with STING, attenuates the STING–TBK1 association, and impairs STING oligomerization and aggregation and STING‐mediated autophagy; ORF10 also prevents the endoplasmic reticulum (ER)‐to‐Golgi trafficking of STING by anchoring STING in the ER. Taken together, these findings suggest that SARS‐CoV‐2 ORF10 impairs the cGAS–STING signaling by blocking the translocation of STING and the interaction between STING and TBK1 to antagonize innate antiviral immunity.
Workforce management in the post‐pandemic era: Evidence from multinational companies using grounded theory
Authors: Khor Lay Kheng , Tan Cheng Ling
Published: June 2022

The COVID‐19 outbreak has significantly altered the conditions of the workforce in operation on an unprecedented scale with companies being pressured to operate digitally and remotely under volatile and unpredictable circumstances. This qualitative study aims to ascertain the (i) key determinants derived from workforce management post‐COVID and (ii) the organizational potentialities and barriers among Malaysian multinational corporations (MNCs) for a holistic understanding of the local workforce post‐pandemic. Four themes (business disruption and operational changes, technology, work from home or WFH, and organizational support) were highlighted using thematic analysis. The current research has offered pivotal insights into and recommendations on operations management opportunities and future study avenues.
Building a pharmacy workforce from the ground up to support the COVID‐19 vaccine rollout: lessons learned and recommendations
Authors: Patanwala Asad E. , Burke Rosemary , McNamara Alexander , Aslani Parisa , McLachlan Andrew J.
Published: June 2022

The COVID‐19 pandemic has required an unprecedented surge in the pharmacy workforce to support mass vaccination hubs. This review discusses the challenges faced while training and credentialing a surge pharmacy workforce and how these challenges were overcome. The process used for training and credentialing new employees has been described and recommendations and insights have been provided based on the lessons learned at two COVID‐19 mass vaccination hubs in New South Wales. Operationalising one of the largest mass vaccination hubs in Australia required efficient training and credentialing of the pharmacy workforce. This process included the use of pharmacist‐extenders such as students, assistants, and those from other healthcare and non‐healthcare backgrounds. Training was optimised by using a flipped classroom model, so that the vaccine preparation process was provided via asynchronous online videos. The videos covered each step of vaccine dose preparation with visual cues to guide appropriate technique. On‐site training involved use of simulation and checklists for credentialing. Many factors contributed to the success of this process, including the use of triaging and the re‐allocation of personnel based on skill level, collaboration with the Sydney Pharmacy School to train and support a surge workforce involving students, initial on‐site information technology support in the form of pharmacy superusers, the use of checklists and guides for troubleshooting, and assigned pharmacy educators to train new employees. The public health response to the COVID‐19 pandemic forced us to rapidly adapt to build a pharmacy workforce in record time to support mass vaccination hubs. The recommendations and insights provided from our experience can guide future surges. Some of these concepts may also be applied to pharmacy practice in hospitals when resources are constrained.
Inhibition of U‐II/UT signaling ameliorates cystitis‐associated bladder hyperactivity by targeting the RhoA/Rho‐kinase pathway
Authors: Liu Qian , Lu Qu‐Dong , Sun Bi‐Shao , Zhao Jiang , He Fan , Zhu Jing‐Zhen
Published: June 2022

Urotensin II (U‐II) and its receptor (UT) are involved in the pathogenesis of various diseases; however, their association with the development of cystitis has not been elucidated. The present study was designed to investigate the functional role of U‐II/UT signaling in cyclophosphamide (CYP)‐induced cystitis. A total of 60 female rats were randomly divided into the control and CYP‐treated groups. Intraperitoneal injection of CYP successfully induced cystitis in rats of the CYP‐treated group. The protein and mRNA expression levels of U‐II and UT were significantly enhanced in rat bladder tissues of the CYP‐treated group. Furthermore, the results of the immunofluorescence staining analysis demonstrated that CYP treatment apparently increased the expression levels of UT in the urothelium layer, detrusor smooth muscle, and bladder interstitial Cajal‐like cells. The selective antagonist of UT, SB657510 (10 μm), significantly suppressed the CYP‐induced increase in the spontaneous contractions of muscle strips and ameliorated the bladder hyperactivity of CYP‐treated rats. Moreover, CYP treatment significantly increased the protein expression levels of Ras homolog family member (Rho) A and Rho‐associated protein kinase 2 in rat bladder tissues. Following pretreatment with the Rho‐kinase inhibitor Y‐27632 (10 μm), the inhibitory effects of SB657510 (10 μm) on the spontaneous contractions of muscle strips were eliminated. In conclusion, the results of the present study suggested that activation of U‐II/UT signaling promoted the development of cystitis‐associated‐bladder hyperactivity by targeting the RhoA/Rho‐kinase pathway, indicating that the U‐II/UT signaling could serve as a novel target for the treatment of interstitial cystitis/bladder pain syndrome.
Fabrication of a Tailored, Hybrid Extracellular Matrix Composite
Authors: Setiawati Agustina , Jeong Sungwoo , Brilian Albertus Ivan , Lee Sang Ho , Shim Jin‐Gon , Jung Kwang‐Hwan , Shin Kwanwoo
Published: June 2022

The extracellular matrix (ECM) is a network of connective fibers that supports cells living in their surroundings. Native ECM, generated by the secretory products of each tissue's resident cells, has a unique architecture with different protein composition depending on the tissue. Therefore, it is very difficult to artificially design in vivo architecture in tissue engineering. In this study, a hybrid ECM scaffold from the basic structure of fibroblast‐derived cellular ECMs is fabricated by adding major ECM components of fibronectin (FN) and collagen (COL I) externally. It is confirmed that while maintaining the basic structure of the native ECM, major protein components can be regulated. Then, decellularization is performed to prepare hybrid ECM scaffolds with various protein compositions and it is demonstrated that a liver‐mimicking fibronectin (FN)‐rich hybrid ECM promoted successful settling of H4IIE rat hepatoma cells. The authors believe that their method holds promise for the fabrication of scaffolds that provide a tailored cellular microenvironment for specific organs and serve as novel pathways for the replacement or regeneration of specific organ tissues.
Mass spectrometry in the discovery of peptides involved in intercellular communication: From targeted to untargeted peptidomics approaches
Authors: Fan Kai‐Ting , Hsu Chia‐Wei , Chen Yet‐Ran
Published: June 2022

Endogenous peptide hormones represent an essential class of biomolecules, which regulate cell–cell communications in diverse physiological processes of organisms. Mass spectrometry (MS) has been developed to be a powerful technology for identifying and quantifying peptides in a highly efficient manner. However, it is difficult to directly identify these peptide hormones due to their diverse characteristics, dynamic regulations, low abundance, and existence in a complicated biological matrix. Here, we summarize and discuss the roles of targeted and untargeted MS in discovering peptide hormones using bioassay‐guided purification, bioinformatics screening, or the peptidomics‐based approach. Although the peptidomics approach is expected to discover novel peptide hormones unbiasedly, only a limited number of successful cases have been reported. The critical challenges and corresponding measures for peptidomics from the steps of sample preparation, peptide extraction, and separation to the MS data acquisition and analysis are also discussed. We also identify emerging technologies and methods that can be integrated into the discovery platform toward the comprehensive study of endogenous peptide hormones.
Anatomical validation of automatic respiratory motion correction for coronary 18F‐sodium fluoride positron emission tomography by expert measurements from four‐dimensional computed tomography
Authors: Lassen Martin Lyngby , Tzolos Evangelos , Pan Tinsu , Kwiecinski Jacek , Cadet Sebastien , Dey Damini , Berman Daniel , Slomka Piotr
Published: June 2022

Background

Respiratory motion correction is of importance in studies of coronary plaques employing 18F‐NaF; however, the validation of motion correction techniques mainly relies on indirect measures such as test–retest repeatability assessments. In this study, we aim to compare and, thus, validate the respiratory motion vector fields obtained from the positron emission tomography (PET) images directly to the respiratory motion observed during four‐dimensional cine‐computed tomography (CT) by an expert observer.

Purpose

To investigate the accuracy of the motion correction employed in a software (FusionQuant) used for evaluation of 18F‐NaF PET studies by comparing the respiratory motion of the coronary plaques observed in PET to the respiratory motion observed in 4D cine‐CT images.

Methods

This study included 23 patients who undertook thoracic PET scans for the assessment of coronary plaques using 18F‐sodium fluoride (18F‐NaF). All patients underwent a 5‐s cine‐CT (4D‐CT), a coronary CT angiography (CTA), and 18F‐NaF PET. The 4D‐CT and PET scan were reconstructed into 10 phases. Respiratory motion was estimated for the non‐contrast visible coronary plaques using diffeomorphic registrations (PET) and compared to respiratory motion observed on 4D‐CT. We report the PET motion vector fields obtained in the three principal axes in addition to the 3D motion. Statistical differences were examined using paired t‐tests. Signal‐to‐noise ratios (SNR) are reported for the single‐phase images (end‐expiratory phase) and for the motion‐corrected image‐series (employing the motion vector fields extracted during the diffeomorphic registrations).

Results

In total, 19 coronary plaques were identified in 16 patients. No statistical differences were observed for the maximum respiratory motion observed in x, y, and the 3D motion fields (magnitude and direction) between the CT and PET (X direction: 4D CT = 2.5 ± 1.5 mm, PET = 2.4 ± 3.2 mm; Y direction: 4D CT = 2.3 ± 1.9 mm, PET = 0.7 ± 2.9 mm, 3D motion: 4D CT = 6.6 ± 3.1 mm, PET = 5.7 ± 2.6 mm, all p ≥ 0.05). Significant differences in respiratory motion were observed in the systems’ Z direction: 4D CT = 4.9 ± 3.4 mm, PET = 2.3 ± 3.2 mm, p = 0.04. Significantly improved SNR is reported for the motion corrected images compared to the end‐expiratory phase images (end‐expiratory phase = 6.8±4.8, motion corrected = 12.2±4.5, p = 0.001).

Conclusion

Similar respiratory motion was observed in two directions and 3D for coronary plaques on 4D CT as detected by automatic respiratory motion correction of coronary PET using FusionQuant. The respiratory motion correction technique significantly improved the SNR in the images.
Sexual harassment policies in nonprofits
Authors: Ma Yinglin , Beaton Erynn E. , Bhati Abhishek
Published: June 2022

The nonprofit sector strives to be a virtuous and transparent space, one that is diverse, inclusive, and welcoming. Still, inappropriate and exclusionary behaviors can and do occur in nonprofits—one of which is sexual harassment (SXH). Currently, little research on SXH in the nonprofit sector exists, and even less is known about the steps taken by nonprofits to protect their employees and stakeholders from SXH. This study examines rates of SXH policy adoption among nonprofits and the relationship between SXH policy adoption and organizational characteristics. Drawing from a state‐wide survey, we find that there is wide variation among nonprofits in their adoption of a written SXH policy. Organizations that have full‐time employees, more revenue, and greater capacity are more likely to have a policy. Organizations that serve women are no more likely to have a policy; however, lesbian, gay, bisexual, and transgender‐serving organizations are more likely to have a policy. We discuss the implications of these results, including the conceptualization of SXH as part of the broader issues of discrimination, harassment, and bullying in nonprofits.
Progress in the mechanical enhancement of hydrogels: Fabrication strategies and underlying mechanisms
Authors: Lin Xuan , Zhao Xianwei , Xu Chongzhi , Wang Lili , Xia Yanzhi
Published: June 2022

Hydrogels have become ideal materials in the nascent applications of tissue engineering, soft robots, drug delivery, and so forth. However, compared with biological tissues, the inherent heterogeneous microstructure and low density of polymer chains make hydrogels mechanically weak, severely limiting their use as structural materials. In recent decades, in order to meet the mechanical requirements of load‐bearing biomaterials, significant research effort have been devoted to improving the mechanical parameters of hydrogels. To achieve this goal, fiber/fabric reinforced hydrogels, double network hydrogels, supramolecular‐interaction‐based hydrogels, hydrogels with well‐aligned microstructures, and solvent induced robust hydrogels have been investigated. In this review, the fabrication strategies, the relationships between the structure and the mechanical properties of the resulting hydrogel, and the underlying enhancement mechanisms in various classes of hydrogel have been summarized. Here, the mechanisms behind these strategies rely on creating the mechanically effective networks, which are achieved by introducing a rigidly reinforced phase, synergistic network with distinctive features, sacrificial bonds, oriented hierarchical structures, or increased supramolecular interactions. Despite significant achievements toward strong and tough hydrogels, considerable important challenges remain, such as simultaneously achieving high strength, toughness, and high water content of hydrogels. It is believed that the already proposed strategies will push the development of hydrogels.
The prognostic role of lymph node dissection counts in the management of renal cell carcinoma: A large international cohort study
Authors: Qi Feng , Wei Xiyi , Xia Xin , Qin Zongshi , Li Xiao
Published: June 2022

The count of lymph node dissection (LND) has been confirmed as a prognostic indicator in various cancers while the correlation between LND counts and patient prognosis in renal cell carcinoma (RCC) was not fully studied. This research evaluated the link between LND counts and the prognosis of RCC patients. This study obtained RCC patients from the SEER database between 2010 and 2014. Univariate and multivariate Cox regression analyses were used to assess the predictive and prognostic value of LND. Besides, Kaplan–Meier (KM) survival analysis was used for survival analysis. Finally, 1264 patients were included in this study, which were divided into none LND groups (249), 1–3 LND groups (166), and 4 or more LND groups (549). Age, laterality, stage, M stage, and grade were statistically different among the three groups. In univariate Cox analysis, stage, M stage, T stage, and grade were significantly correlated with overall survival (OS). In multivariate Cox regression analysis, age, race, stage, T stage, and grade were used as independent prognostic factors. KM survival analysis revealed that grade, T stage, M stage, and stage were significantly correlated with OS. Subgroup analysis revealed that LND counts were not significantly associated with survival risk in subgroups with different clinical factors. The current North American population analysis revealed that age, race, stage, T stage, and grade may be used as independent prognostic factors for patients with RCC. Moreover, the increasing LND counts during surgery may not improve the tumor outcomes of RCC patients.
Preparation and characterization of emamectin benzoate nanocapsules based on the dual role of polydopamine
Authors: Shi Liyin , Yan Weiyao , Sun Li , Hou Chaoqun , Wei Nuo , Chen Zhiyang , Feng Jianguo
Published: June 2022

Background

Developing pesticide‐controlled release formulations with foliage adhesion has become the focus of current research in the field of crop protection. In this study, an excellent adhesive nanocapsule loaded with emamectin benzoate (Eb@PDA) was prepared via emulsion interfacial polymerization based on the self‐polymerization ability and adhesion properties of polydopamine (PDA).

Results

The physicochemical properties of the Eb@PDA were characterized by scanning electron microscopy, transmission electron microscopy, particle size statistics, Fourier transform infrared spectroscopy and X‐ray diffraction. The Eb@PDA presented a regular spherical shape, with an average particle size of 163.8 nm. Compared with conventional formulations, it had higher pesticide‐loading content (34%) and excellent adhesion onto corn leaf. In addition, Eb@PDA showed sustained‐release characteristics, facilitating the release of Eb at low pH and high temperature. Eb@PDA could effectively protect Eb against photodegradation and had a longer effective period for controlling Spodoptera frugiperda and Spodoptera exigua. Furthermore, acute toxicity tests showed that the 50% lethal concentration (LC50) was 80.91 and 57.91 mg kg−1 at 7 and 14 days, respectively, indicating a lower toxicity of the Eb@PDA to earthworms. The cells (L02) treated with Eb@PDA showed a higher cell viability but a lower apoptosis rate (only 5.75%), demonstrating the lower cytotoxicity of the Eb@PDA.

Conclusion

The self‐prepared Eb@PDA could be used as a formulation with the advantages of slow release, UV shielding, strong leaf adhesion, superior insecticidal properties, sustained effectiveness and biosafety. It will also facilitate the development of an efficient and safe pesticide delivery system. © 2022 Society of Chemical Industry.
Template‐Free Synthesis of 2D‐Pristine VS4 Nanosheets for Supercapacitor Applications
Authors: Rajendran Kumuthini , Nagamony Ponpandian , Annal Therese Helen
Published: June 2022

Transition metal chalcogenides with 1D crystal structures such as FeS2, NiS2, CoS2, and VS4 have sparked significant investigation because of their fascinating physical, chemical, and electrochemical characteristics. VS4, a quasi‐1D linear chain‐like structure with good electrochemical behavior, has piqued the curiosity of many researchers in recent years. The synthesis of the pristine form of VS4 as well as its electrochemical behavior for supercapacitor (SC) applications is presented here. The vanadium tetrasulfide (VS4) nanosheets are synthesized in larger quantities using a simple, template free, and scalable one‐pot hydrothermal process. The physicochemical properties of the VS4 were studied using X‐ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, and high‐resolution transmission electron microscopic analysis. The electrochemical performance of the material is investigated as an electrode for SCs. The electrode exhibits the maximum capacitance of 215 F g−1 at the scan rate of 5 mV s−1 with the capacitance retention of 82% for 2000 cycles.
Understanding sources of Northern Hemisphere uncertainty and forecast error in a medium‐range coupled ensemble sea‐ice prediction system
Authors: Peterson K. Andrew , Smith Gregory C. , Lemieux Jean‐François , Roy François , Buehner Mark , Caya Alain , Houtekamer Pieter L. , Lin Hai , Muncaster Ryan , Deng Xingxiu , Dupont Frédéric , Gagnon Normand , Hata Yukie , Martinez Yosvany , Fontecilla Juan Sebastian , Surcel‐Colan Dorina
Published: June 2022

The Global Ensemble Prediction System (GEPS) of Environment and Climate Change Canada was recently upgraded to a coupled atmosphere, ocean, and sea‐ice version from an uncoupled atmosphere‐only system. This has been operational since July 2019, with over a year of forecasts now available to evaluate the system throughout all seasons. Using metrics that score the forecast error in ice‐edge position, the spatial probability score and the integrated ice‐edge error, we investigate the spread–error relationship in probabilistic Arctic sea‐ice forecasts from the system and compare this with the skill of the system relative to persistence and a companion Global Deterministic Prediction System (GDPS). Within this ensemble framework, we explore the advantages of having a probabilistic forecast and probe its usefulness in addressing the errors in the system. Both the ensemble GEPS and the deterministic GDPS systems show enhanced sea‐ice prediction over persistence in all months except May and June, when significant biases exist in the systems in shallow‐sea and shelf regions. We attribute a significant portion of these biases to problems modelling landfast ice, but other sources of bias, including significant uncertainties in initializing and verifying sea‐ice analysis, also contribute. The lowest errors in the systems are found during September and continue at reasonably low levels through much of the boreal winter. The minimum and maximum extent periods, along with the early freeze‐up period, are shown to be periods for which the ensemble system offers enhanced benefits over a single deterministic forecast. For these periods, the errors are low and strongly correlated spatially with the ensemble spread. Nevertheless, we find that the ensemble system would likely still benefit from further improvement of the spread/error relationship in the system, currently hampered due to ensemble perturbations that are produced solely in the atmospheric component.
Application of automated and robotically deployed in situ X‐ray fluorescence analysis for nuclear waste management
Authors: White Samuel R. , Martin Peter G. , Megson‐Smith David A. , Scott Thomas B.
Published: June 2022

Laboratory and synchrotron X‐ray fluorescence (XRF) analysis has both served as mainstay rapid and quantitative elemental analysis techniques for decades, attaining parts per million sensitivities for the majority of elements. Formerly, XRF was the reserve of large X‐ray generating systems and national facilities. More recently, developments in miniaturized X‐ray generators and detectors have allowed for this nondestructive technique to be utilized for portable and in situ elemental characterization of materials, away from the confines of the laboratory. When combined with a robotic manipulator, these usually handheld systems present a powerful method for autonomous assessments of material composition for a wide range of nuclear characterization and decommissioning scenarios. In this study, we present a proof‐of‐concept XRF system integrated with a robotic manipulator to autonomously identify a suite of nuclear relevant materials. Such remotely deployable noncontact tools are crucial for use within hazardous environments where it may not be possible, for physical and safety reasons, for a human operator to manually undertake characterization tasks. It is envisaged that this robotically deployed XRF system will comprise part of the wider autonomous characterization “toolkit”; capable of extensive large‐area mapping alongside targeted compositional “point analysis.” The system was demonstrated to rapidly and repeatably derive accurate and precise compositional information of different test materials, autonomously on both flat and complex, object‐rich surfaces.