bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrophile‐Promoted Nucleophilic Cyclization of 2‐Alkynylindoles to Give 4‐Substituted Oxazinoindolones
Authors: Leonel Guilherme , Klann Isabella , Back Davi F. , Iglesias Bernardo A. , Nogueira Cristina W. , Zeni Gilson
Published: November 2022

A method for the synthesis of 4‐organoselanyl oxazinoindolone derivatives by the cascade cyclization of N‐(alkoxycarbonyl)‐2‐alkynylindoles using iron(III) chloride and diorganyl diselenides as promoters was developed. This protocol was applied to a series of N‐(alkoxycarbonyl)‐2‐alkynylindoles containing different substituents. The reaction conditions also tolerated a variety of diorganyl diselenides having both electron donating and electron withdrawing groups. However, the reaction did not work for diorganyl disulfides and ditellurides. The reaction mechanism seems to proceed via an ionic pathway and the cooperative action between iron(III) chloride and diorganyl diselenides is crucial for successful cyclization. We also found that using the same starting materials, by simply changing the electrophilic source to iodine, led to the formation of 4‐iodo‐oxazinoindolones. The high reactivity of Csp2−Se and Csp2−I bonds were tested under cross‐coupling conditions leading to the preparation of a new class of functionalized indole derivatives. In addition, the absorption, emission and electrochemical properties of 4‐organoselanyl oxazinoindolones showed an important relationship with the substituents of the aromatic rings. The advantages of the methodology include the use of electrophilic to promote the cyclization reaction and functionalization of the indole ring, and the electronic properties presented by the prepared compounds can be exploited as probes, analyte detectors and optical materials.
Design and Synthesis of a Ferrocene‐Based Diol Library and Application in the Hetero‐Diels‐Alder Reaction
Authors: Cunningham Laura , Guiry Patrick J.
Published: November 2022

Diol scaffolds have been utilized as highly effective catalysts and ligands in a wide range of catalytic asymmetric transformations. For scaffolds to be successful as broadly used motifs, they should be prepared cheaply through facile routes and be easily handled. Herein, the synthesis of a family of planar chiral diols based on a modular and robust three‐step route is described, which yields catalytically active diols in >99 % de and >99 % ee, with up to seven different chiral elements. These diols have been characterized by X‐ray crystallographic analysis, which provides clear evidence for the likely transition state when applied in the asymmetric hetero‐Diels‐Alder reaction. Without altering the stereochemistry of the catalyst backbone, it is possible to access both enantiomers of the product by varying the substitution of the catalyst at the α‐position.
Ion Migration and Accumulation in Halide Perovskite Solar Cells†
Authors: Zuo Lijian , Li Zexin , Chen Hongzheng
Published: November 2022

Comprehensive Summary

The halide perovskite semiconductors‐based solar cells (PVSCs) show great promise as next‐generation renewable energy sources, with the merits of low cost, high performance, good flexibility, etc. A major difference distinguishing the perovskite semiconductors from others lies in their ionic feature. This intrinsic property induces “freely‐moving” ions to migrate and accumulate in the perovskite films and devices under different external stresses. As a charge carrier, these processes will strongly couple with the electronic process, and dramatically affect the performance and stability of PVSCs. This review summarizes and discusses the recent progresses and fundamental understandings of ion migration and accumulation behaviors in PVSCs. First, the basic principles of the general ion migration are reviewed. Second, following the fundamental understandings, the critical factors, e.g., ion migration activation energy, ion density, ion diffusion coefficient, etc., are extracted to understand the ion migration and accumulation in perovskite film. Third, the principles governing ion accumulation behaviors under different external stresses are discussed. Finally, the effect of ion migration and accumulation on band bending, and device performance is presented. Therefore, we hope this review provides a tutorial and insightful perspective regarding the most prominent ionic feature of perovskite semiconductors and their application for photovoltaics.
Nucleophilic Radicals as Hydrogen Atom Abstractors in C(sp3)‐H Functionalization Reactions
Authors: Li Tao , Li Jian , Huo Haohua
Published: November 2022

Comprehensive Summary

Hydrogen atom transfer (HAT) is an elementary mechanistic step in organic synthesis. The photoredox‐catalyzed HAT has transformed organic synthesis by enabling the activation and subsequent cross‐coupling of traditionally inert yet ubiquitous C(sp3)‐H bonds. While diverse electrophilic radical species have proven to be exceptionally effective HAT catalysts for selective functionalization of hydridic and electron‐neutral C(sp3)‐H, general methods using nucleophilic radicals as hydrogen atom abstractors in C(sp3)‐H functionalization remain relatively underdeveloped. Herein, we highlight two creative and strategic advances in addressing this long‐standing challenge, and emphasize reaction achievements, mechanistic insights, potential, and future challenges.
Design and Synthesis of N‐Alkylaniline‐Substituted Low Band‐Gap Electron Acceptors for Photovoltaic Application
Authors: Li Jiayao , Li Hao , Ma Lijiao , Zhang Shaoqing , Hou Jianhui
Published: November 2022

Comprehensive Summary

A novel electron donating unit, namely N‐octyl‐N‐phenyl‐thiophene (OPT), was designed in preparing electron acceptors with non‐fused ring chemical structures. By introducing different functional atoms/groups into the para‐position of phenyl in the OPT units, three non‐fused ring acceptors (NFREAs), C8‐2F, FC8‐2F and MeC8‐2F, were synthesized. The absorption spectrum of the three acceptors can be extended to about 950 nm with band‐gaps of 1.28—1.32 eV due to the strong electron donating ability of OPT. The frontier molecular orbital distribution of OPT based molecules obtained by quantum chemistry calculation results reveals that their energy alignment can be finely tuned to meet different requirements. Moreover, by changing the substituents on the OPT units, their Flory‐Huggins interaction parameter (χ) with the donor will be greatly influenced and different phase separation behavior can be accomplished. After blended with PBDB‐TF, the FC8‐2F‐based cell yields short circuit current density (Jsc) of 23.21 mA·cm–2, fill factor (FF) of 72.11% and the highest power conversion efficiency (PCE) of 12.42%. This work provides a new pathway for molecular design of new NFREAs, and demonstrates the application potential of OPT unit in realizing low band‐gap photovoltaic materials.
Design and Synthesis of Al7Ni2 Heterometallic Clusters Based on Metal Substitution and Ligands Protection Strategies†
Authors: Liu Ya‐Jie , Cui Li‐Min , Fang Wei‐Hui , Zhang Jian
Published: November 2022

Comprehensive Summary

The synthesis of heterometallic aluminum‐based materials is challenging yet attractive, due to their potential applications in optics, catalysis, magnetism and semiconductor device. We have now successfully synthesized two Al7Ni2 heterometallic clusters bearing different peripheral alkoxide ligands through a heterometal substitution strategy. Single crystal structure analysis shows that they are isostructural, only with slight differences in the number of OH and guests. We found that benzyl alkoxides protected Al7Ni2 cluster compound is more stable in H2O and various organic solvents when compared with ethoxides coordinated one. Moreover, it can be used as a reliable catalyst in aldol condensation reactions with higher activity. This work provides a new method for the design of stable crystalline heterometallic aluminum oxo compounds and reveals their excellent catalysis performance.
Lightweight, secure, efficient, and dynamic scheme for mutual authentication of devices in Internet‐of‐Things‐Fog environment
Authors: Jain Usha , Pirasteh Saied , Hussain Muzzammil
Published: November 2022

Security is a major challenge in the design and implementation of Internet‐of‐Things (IoT)‐Fog networks and it can be resolved by an efficient authentication mechanism. As the devices have limited resources like battery, processor and memory, any mechanism designed for IoT‐Fog has to be resource aware. In this paper, we proposed a lightweight, secure, dynamic, and efficient scheme for mutual authentication of devices in IoT‐Fog networks. In the proposed scheme, the devices obtain a primary security value from the cloud server and this acquired primary security value is used to authenticate them mutually. We used XOR operation, concatenation operation, one‐way hash function and symmetric key cryptography to accommodate resource constraint nature of devices. The proposed scheme has been analyzed for security formally using BAN logic and automated using Automated Validation of Internet Security Protocols and Applications & ProVerif tools and it is proved that the proposed scheme is secure from the known attacks. The comparative analysis of the proposed scheme with the existing schemes proved that it is better than existing schemes and its experimental analysis showed that it consumes 20%–30% less energy compared to existing schemes. Our proposed scheme is better with reference to security and efficient in respect of computation, communication, and storage overheads.
A Constitutive Model for Polycrystalline U–Nb Alloy Considering Multiple Phase Transition
Authors: Liu Tingyi
Published: November 2022

This study proposes a thermomechanical constitutive model for the shape memory effect of U–12.8 at.% Nb (U–Nb) alloy. The phenomenological model uses two variables for transformation. A transitional evolution function based on dissipative force is constructed, which removes the consistency condition. This improvement leads to a natural smoothness of all transitions, without any specifically defined hardening function. In addition, hysteresis is a natural result of the same reference force being converted forward and backward, and defining two different mixing energies is not necessary. The effect of strain rate is captured in the same frame by a function of the transition coefficient. This paper designs a robust and efficient numerical algorithm for the ordinary differential equation system. The model is validated by several special load cases. The simulation results are then compared with previous experimental data in the paper.
Modulated relay based stable election protocol for large‐scale wireless sensor networks
Authors: Hamad Lana I. S. , Dag Tamer , Gucluoglu Tansal
Published: November 2022

Internet of things (IoT) applications based on wireless sensor networks (WSNs) have recently gained vast momentum. These applications vary from health care, smart cities, and military applications to environmental monitoring and disaster prevention. As a result, energy consumption and network lifetime have become the most critical research area of WSNs. Through energy‐efficient routing protocols, it is possible to reduce energy consumption and extend the network lifetime for WSNs. Using hybrid routing protocols that incorporate multiple transmission methods is an effective way to improve network performance. This paper proposes modulated R‐SEP (MR‐SEP) for large‐scale WSN‐based IoT applications. MR‐SEP is based on the well‐known stable election protocol (SEP). MR‐SEP defines three initial energy levels for the nodes to improve the network energy distribution and establishes multi‐hop communication between the cluster heads (CHs) and the base station (BS) through relay nodes (RNs) to reduce the energy consumption of the nodes to reach the BS. In addition, MR‐SEP reduces the replacement frequency of CHs, which helps increase network lifetime and decrease power consumption. Simulation results show that MR‐SEP outperforms SEP, LEACH, and DEEC protocols by 70.2%, 71.58%, and 74.3%, respectively, in terms of lifetime and by 86.53%, 86.68%, and 86.93% in terms of throughput.
Sex‐specific biomarkers in Alzheimer's disease progression: Framingham Heart Study
Authors: Liu Chunyu , Li Yi , Nwosu Adaora , Ang Ting Fang Alvin , Liu Yulin , Devine Sherral , Au Rhoda , Doraiswamy P. Murali
Published: November 2022

Background

Sex differences in Alzheimer's disease (AD) are not well understood.

Methods

We performed sex‐specific analyses of AD and annualized cognitive decline with clinical and blood biomarker data in participants 60+ years old in the community‐based longitudinal Framingham Heart Study Offspring Cohort (n = 1398, mean age 68 years, 55% women).

Results

During 11 years of follow‐up, women were 96% more likely than men to be diagnosed with clinical AD dementia after adjusting for age and education in the younger age group 60 to 70 years (n = 946; 95% confidence interval [CI], 1.08 to 3.56) although not in the older age group (70+) (n = 452; hazard ratio = 0.98; 95% CI, 0.68 to 1.53). Sex‐differences in incident AD rates decreased with increasing levels of education. The total contribution of the biomarkers to AD risk variance was 7.6% in women and 11.7% in men. One unit (pg/ml) lower plasma Aβ42 was associated with 0.0095 unit faster memory decline in women (p = 0.0002) but not in men (p = 0.55) after adjusting for age and education.

Discussion

Our study suggests that both early life and later‐life pathological factors may contribute to potential sex differences in incident AD.
Neuroprotective effects of nerolidol against Alzheimer's disease in Wistar rats
Authors: Taheri Peyman , Yaghmaei Parichehreh , Hajebrahimi Zahra , Parivar Kazem
Published: November 2022

Alzheimer's disease (AD) is the most common type of cognitive disorder in an elderly population associated with the accumulation of amyloid plaques and neurofibrillary tangles. Nerolidol is assumed to have neuroprotection effects. This study aimed to investigate the therapeutic effects of nerolidol on the Aβ‐induced model of AD in rats. Hippocampal injection of Aβ was used to induce AD. Animals were randomly divided into control, sham (received PBS as Aβ solvent), AD, DNPZ (AD + donepezil, 4 weeks); NRD‐50 (AD + nerolidol, 50 mg/kg, 4 weeks), NRD‐100 (AD + nerolidol, 100 mg/kg, 4 weeks; Prot (rats which received 100 mg/kg nerolidol for two weeks before Aβ administration), and Solv (AD + sunflower oil as nerolidol solvent, 4 weeks) groups. All rats were subjected to a memory behavioral passive avoidance test by shuttle box. Thioflavin‐S staining was performed to confirm Aβ plaque formation and measured using ImageJ analyzing program. BDNF and CREB‐1 expressions were analyzed by immunohistochemistry assay. Aβ induced AD by Aβ plaques formation and increasing step‐through latency time. It reduced the expression of BDNF and CREB‐1 protein. Administration of nerolidol or donepezil improved these features by decreasing Aβ and increasing BDNF and CREB‐1 expression and latency time. Nerolidol is likely to provide protection against AD. It may prevent dementia through the mediation of BDNF‐CREB‐1 expression and cholinergic nerve cells restoring. It seems that the administration of nerolidol before the onset of the disease will be more effective than after.
Nintedanib‐αVβ3 Integrin Ligand Dual‐Targeting Conjugates towards Precision Treatment of Melanoma
Authors: Bugatti Kelly , Sartori Andrea , Battistini Lucia , Ruzzolini Jessica , Nediani Chiara , Curti Claudio , Bianchini Francesca , Zanardi Franca
Published: November 2022

Melanoma is the deadliest form of skin cancer, and more than 150,000 cases are diagnosed every year in Europe. New strategies in treatment approved over the past decade, such as immunotherapy and targeted therapy, have prolonged life expectation even in stage IV melanoma patients. However, due to the increasing incidence of this cancer, the development of new therapeutic strategies remains urgent. Recent studies revealed the combination of nintedanib, a tyrosine kinase inhibitor approved as an antifibrotic drug, and immuno‐ and/or targeted therapy drugs to be promising. Here we present three new dual covalent conjugates, in which a nintedanib unit is permanently linked to a cyclopeptidomimetic ligand for the αVβ3 integrin, a transmembrane receptor involved in cell survival, proliferation and migration, which is overexpressed by tumour cells, and therefore recognized as marker for tumour targeting. In vitro assays on human melanoma tumour cells confirmed the high binding affinity of these conjugates for αVβ3 integrin‐positive melanoma cells, as well as their integrin‐mediated cell internalization. Two of these conjugates were efficient in inhibiting the mitogen activated protein kinase (MAPK) signalling pathway, common to both integrin‐ and growth factor‐ biological targets. Such targeted conjugates could therefore be of special interest in melanoma treatment alone or in combination with other anticancer drugs.
Identification of main factors affecting mechanical characteristics of silicon carbide sludge‐based geopolymer via experimental design and associated statistical analysis
Authors: Lo Kang‐Wei , Lin Kae‐Long , Lin Ya‐Wen , Cheng Ta‐Wui
Published: November 2022

Despite considerable research in geopolymer materials, the design of experiment (DOE) method has not previously been used for the analysis of geopolymers containing silicon carbide sludge (SCS) waste and/or metakaolin (MK). This study used DOE methods to quantitatively assess the correlation between factor parameters and the macroscopic and microstructural properties of SCS‐based geopolymers (SCSGPs). Statistical analysis identified Na/Si molar ratio, Na/Al molar ratio, and the dissolution rate of Al as the factors with the most profound influence on the compressive strength of the SCSGPs. Analysis of setting time and compressive strength revealed that in SCSGP samples containing 20% SCS, coefficient b in power function regression analysis was the most influential, due to the synergy between MK and SCS. The results obtained in this study using a multivariate adaptive regression splines model to establish a valuable reference for the further development and standardization of geopolymer mixture designs based on SCS.
Work‐relatedness of carpal tunnel syndrome: Systematic review including meta‐analysis and GRADE
Authors: Hassan Awa , Beumer Annechien , Kuijer P. Paul F. M. , van der Molen Henk F.
Published: November 2022

Background and Aims

Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment syndrome with a high prevalence among workers. Insights on the physical work‐related risk factors is necessary to develop appropriate preventative methods. The objective of this systematic review, including meta‐analyses, is to assess which physical work‐related risk factors are associated with carpal tunnel syndrome.

Methods

Systematic literature searches were carried out using PubMed and Embase until September 6, 2021. Studies were included if: (1) CTS was clinically assessed, (2) the studies were prospective cohort studies, and (3) the exposure was reported using terms of exposed/less or nonexposed. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE).

Results

In total, 9270 patients with CTS from a population of 1,051,707 workers were included from 17 studies. Meta‐analyses revealed high‐quality evidence for associations between CTS and high exposures to repetition (hazard ratio [HR] 1.87, 95% CI 1.42–2.46), force intensity (HR 1.84, 95%CI 1.22–2.79), exposures above hand activity level of ACGIH (HR 1.75, 95%CI 1.40–2.17), and the Strain Index >10 (HR 1.58, 95% CI 1.09–2.30). No significant associations were found for pinch gripping, hand‐arm vibration or force duration. High computer‐use exposure was significantly associated with a decreased rate of work‐related CTS (HR 0.28, 95% CI 0.12–0.64).

Conclusion

This systematic review of prospective cohort studies found high certainty for an increased rate of CTS due to a high Strain Index, exposures exceeding the Activity Level of ACGIH, and high force intensity and high repetition. Workers performing tasks requiring both high force and high repetition even have a higher rate of developing CTS.
Minority versus majority: The choice of acquisition in Asia‐Pacific countries
Authors: Nguyen Ann‐Ngoc , Kernohan David , Nguyen Tung
Published: November 2022

This paper examines the relationship between the financial constraints of the acquiring firms and their choice of a minority over a majority acquisition. Our findings show that the likelihood of bidders undertaking a minority acquisition increases with financial constraints, including the deviation from target capital structure, and overleverage deficit. We also find that the impacts of leverage deviation on the likelihood of bidders engaging in a minority or majority acquisition is asymmetric for underleveraged and overleveraged firms. In addition, international bidders are less likely to take a minority acquisition if the target is operating in (i) countries with a higher degree of Political Stability and Absence of Violence/Terrorism, (ii) countries with higher degree to which individuals are able to participate in selecting their government, as well as having more freedom of expression, freedom of association, and a free media. Lastly, minority acquisitions are more common in a country with a more developed market. As such, in a fluid social order it looks like acquirers really need majority control.
Climate change and women's health: Turning leadership into action
Authors: Conry Jeanne , Robson Steve
Published: November 2022

Climate change is considered the greatest long‐term challenge we face, and it comes with a direct impact on women's health and pregnancy outcomes. There are many balances that physicians make in deciding elements of care, but environmental impact has not been a consideration. Health care leaders must recognize the impact of their decisions on carbon footprints and creatively look towards changes that will improve global conditions.
Exploring institutional logics to dynamic ambidexterity in health information system implementation in the public health sector of Ethiopia
Authors: Woldeyohannes Birkinesh , Gaynor Mark , Assefa Temtim
Published: November 2022

Information system (IS) implementation can often lead to inherently contradictory issues, standardization, and evolve‐ability, which requires different, sets of information technology (IT) governance mechanisms. Recent research advocate ambidexterity mechanisms which consider the contradictory logic for long‐term success yet it has paid little attention to resource‐constrained settings which is a source of contradiction for the lack of technical and financial resource. Using an interpretative approach, based on institutional logic and dynamic ambidexterity concepts, this study revealed how centralized, systemic, and IT logics shaped IT governance mechanisms toward centralized and ad hoc‐based decentralized structures. Furthermore, the study depicted how the lack of a common vision for IS implementation impeded defining roles, identifying and collaborating with similar initiatives that led the implementation to uncontrolled evolve‐ability. Despite the absence of a common vision in resource‐constrained settings, the study identified the importance of resource‐chasing collaboration among heterogeneous actors to achieve standardization and evolve‐ability at a certain level though not sufficient. The study proposed an ambidextrous implementation framework by combining dynamic ambidexterity and institutional logic concepts to complement the resource‐chased collaboration with major HIS logics‐based collaboration through devising common vision, strategy, and mechanisms which allows sensing, seizing, and reconfiguring the emergent heterogeneous system implementation initiatives to achieve standardization and evolve‐ability simultaneously.
Production network: Application in China
Authors: Yu Dianfan , Long Rui , Wang Chao
Published: November 2022

Based on the input–output table and the supplier–customer data disclosed by the listed companies in China, this paper builds China's production network on both industry level and firm level. We describe the characteristics of such network using various network indexes and obtain the following results: first, China's production network on industry level is featured by “small world” and “sparsity,” and continues to become sparser. The existence of hub‐like sectors makes the influence of sectoral shocks on macro fluctuations increasingly important. Second, China's production network on firm level has three types of structures: horizontal, ring, and star. Automobile and pharmaceutical industries show obvious intra‐industry network cluster features. This paper aims to deepen the understanding of production network on both macro and micro levels, and provide a basis for future study on the propagation of external shocks in production networks.
Implementation science to analyze motivators and barriers to pharmacist‐prescribed contraception in Michigan community pharmacies
Authors: Rashid Zenab H. , O'Connell Mary Beth , Yang Kai
Published: November 2022

Introduction

A public health initiative in the United States is to lower the country's 45% unintended pregnancy rate. Although pharmacist‐prescribed contraception is beneficial, implementation is low. Enhancing motivators and overcoming barriers could increase implementation.

Objectives

To quantify the motivating factors and barriers to pharmacist‐prescribed contraception and compare them by interest in implementing contraception prescribing.

Methods

The Theoretical Domains Framework was used to create an investigator‐developed 41‐item survey. Surveys were mailed to all Michigan independent pharmacies and chain pharmacies granting permission. Descriptive and nonparametric analyses were conducted.

Results

Survey response rate was 11% (N = 147). Pharmacies were independent (39.5%), small independent group (2‐4 stores, 21.8%), large independent group (≥5 stores, 8.8%), national chain (15%), and two grocery store chains (15%). Top motivators to implement this service were to increase scope of practice, patient access to contraception, and pharmacy revenue. Top pharmacist, financial, resource, and safety barriers were contraception knowledge gaps, lack of financial reimbursement, lack of physicians to create a collaborative practice agreement, and increased liability, respectively. Pharmacies wanting to implement this service (n = 85) were early change adopters (P < .001), wanted to implement more direct patient care (P < .001), could create collaborative practice agreements (P < .001), had needed resources (P < .001), and were motivated by competition (P < .001) than pharmacies not wanting to implement this service (n = 61). They also felt their patients would value (P < .001) and use (P < .001) pharmacist‐prescribed contraception. Geographical location, city size, pharmacy type, and prescription volume did not significantly differ between pharmacies wanting to implement or not this service.

Conclusion

Pharmacies wanting to implement pharmacist‐prescribed contraception service had more positive attitudes, and better knowledge, skills, and resources than those not wanting to implement the service. Many implementation barriers existed requiring solutions and advocacy efforts by community pharmacy staff, organizations, and colleges to increase implementation of this service in community pharmacies.
Conditional Loss of Nmp4 in Mesenchymal Stem Progenitor Cells Enhances PTH-Induced Bone Formation
Authors: Atkinson Emily G. , Adaway Michele , Horan Daniel J. , Korff Crystal , Klunk Angela , Orr Ashley L. , Ratz Katherine , Bellido Teresita , Plotkin Lilian I. , Robling Alexander G. , Bidwell Joseph P.
Published: November 2022

Activation of bone anabolic pathways is a fruitful approach for treating severe osteoporosis, yet FDA-approved osteoanabolics, eg, parathyroid hormone (PTH), have limited efficacy. Improving their potency is a promising strategy for maximizing bone anabolic output. Nmp4 (Nuclear Matrix Protein 4) global knockout mice exhibit enhanced PTH-induced increases in trabecular bone but display no overt baseline skeletal phenotype. Nmp4 is expressed in all tissues; therefore, to determine which cell type is responsible for driving the beneficial effects of Nmp4 inhibition, we conditionally removed this gene from cells at distinct stages of osteogenic differentiation. Nmp4-floxed (Nmp4fl/fl) mice were crossed with mice bearing one of three Cre drivers including (i) Prx1Cre+ to remove Nmp4 from mesenchymal stem/progenitor cells (MSPCs) in long bones; (ii) BglapCre+ targeting mature osteoblasts, and (iii) Dmp1Cre+ to disable Nmp4 in osteocytes. Virgin female Cre+ and Cre− mice (10 weeks of age) were sorted into cohorts by weight and genotype. Mice were administered daily injections of either human PTH 1-34 at 30 μg/kg or vehicle for 4 weeks or 7 weeks. Skeletal response was assessed using dual-energy X-ray absorptiometry, micro-computed tomography, bone histomorphometry, and serum analysis for remodeling markers. Nmp4fl/fl;Prx1Cre+ mice virtually phenocopied the global Nmp4−/− skeleton in the femur, ie, a mild baseline phenotype but significantly enhanced PTH-induced increase in femur trabecular bone volume/total volume (BV/TV) compared with their Nmp4fl/fl;Prx1Cre− controls. This was not observed in the spine, where Prrx1 is not expressed. Heightened response to PTH was coincident with enhanced bone formation. Conditional loss of Nmp4 from the mature osteoblasts (Nmp4fl/fl;BglapCre+) failed to increase BV/TV or enhance PTH response. However, conditional disabling of Nmp4 in osteocytes (Nmp4fl/fl;Dmp1Cre+) increased BV/TV without boosting response to hormone under our experimental regimen. We conclude that Nmp4−/− Prx1-expressing MSPCs drive the improved response to PTH therapy and that this gene has stage-specific effects on osteoanabolism. © 2022 American Society for Bone and Mineral Research (ASBMR).
Pirfenidone attenuates nonalcoholic fatty liver disease through activation of the nuclear factor erythroid 2‐related factor 2 (Nrf2) signaling pathway
Authors: Xie Rong , Chen Shaodong , Li Fang , Yang Liu , Yu Bangliang
Published: November 2022

Nonalcoholic fatty liver disease (NAFLD) originates from the hepatopathy of fatty liver. Pirfenidone is a novel broad‐spectrum anti‐fibrosis agent used for treating various kinds of tissue fibrosis. The present study will evaluate the effects of Pirfenidone on liver injury in high‐fat diet (HFD)‐fed mice to evaluate the value of Pirfenidone in treating NAFLD. The pathology of NAFLD was simulated by feeding mice with an HFD in the present study, followed by treating the HFD mice with 150 and 300 mg/kg/day Pirfenidone once a day. The pathological state of HFD mice was identified by the elevated liver weight, promoted serum triglyceride (TG), total cholesterol (TC), and low‐density lipoprotein cholesterol (LDL‐C) levels, declined serum high‐density lipoprotein cholesterol (HDL‐C) levels, increased alanine aminotransferase and aspartate aminotransferase activity, and histopathological changes to the liver tissues, all of which were dramatically ameliorated by 150 and 300 mg/kg Pirfenidone administration. Furthermore, the excessive production of interleukin‐1β (IL‐1β), tumor necrosis factor‐α (TNF‐α), and IL‐6, as well as upregulated phosphorylated nuclear factor kappa‐B (p‐ NF‐κB p65), were observed in HFD‐fed mice, but significantly reversed by Pirfenidone. Finally, activated oxidative stress, identified by promoted malondialdehyde (MDA) levels and declined catalase (CAT) activity, was observed in HFD‐fed mice, accompanied by the downregulation of nuclear factor erythroid 2‐related factor 2 (Nrf2) and sterol‐regulatory element‐binding proteins‐1c (SREBP‐1c). After the treatment with Pirfenidone, oxidative stress was greatly mitigated. Our results imply that Pirfenidone ameliorated the progression of NAFLD by mediating inflammation and oxidative stress.
Are adults influenced by the experience of mentoring youth? A scoping review
Authors: Anderson Amy J. , DuBois David L.
Published: November 2022

Aims

A relatively large body of research exists on the effectiveness of mentoring programs directed at youth and numerous syntheses of this literature have proven useful for advancing both research and practice. Less studied, but also important is the potential for adults serving in the role of mentor to young persons to be influenced by this experience. A scoping review was conducted with the aim of identifying and critically assessing major trends in the methods and findings in this literature.

Methods

Included sources were empirical studies reporting findings that address potential influences on adults (18+) serving as mentors to youth (<18) in formal programs designed for this purpose. The initial search resulted in 3155 records and 96 were included in the review.

Results

Approximately half of the studies (58%) focused on younger adults (ages 18–22 years old, e.g., college students) serving as mentors; only a small minority of studies focused on adults over 35 years old (10%). Most studies were qualitative (n = 54). Studies with a quantitative component (n = 18 quantitative only;n = 24 mixed methods) exhibited a significant risk of bias for inferring effects on mentors due to limitations in study design (e.g., lack of comparison group). Studies most often addressed potential outcomes for mentors in academic/career (55%) and social (45%) domains, when findings suggested possible effects on mentors, they were nearly universally in a positive direction.

Conclusion

Existing research, although consistent with the potential for adults to benefit from the experience of mentoring youth, has insufficient rigor and representativeness to adequately address this question. Future research should utilize more rigorous quantitative designs and samples with greater representativeness of the different stages of adult development.
Ensiling water hyacinth for enhanced biomethane production: effect of co‐ensiling with maize straw and eggshell powder as additive
Authors: Undiandeye Jerome , Kiman Silas , Kefas Haruna Mavakumba , Nelles Michael , Stinner Walter
Published: November 2022

BACKGROUND

The invasion of water hyacinth (WH) on water bodies comes with adverse consequences for humans and the environment. Using WH as a substrate for affordable and clean energy production is one way of controlling the invasiveness of the aquatic plant. In this study, ensiling was carried out with and without the addition of maize straw (MS) and eggshell powder (ES) to determine the effect of higher total solids (TS) and butyric acid contents on the biomethane potential (BMP) of WH. The silages were stored at ambient temperature for 210 days. The kinetics of biomethane production was determined using three different kinetic models.

RESULTS

Ensiled WH without MS and ES had a reduced BMP after 210 days. However, a combination of higher TS (40%) and butyric acid contents, resulting from the addition of MS and ES, significantly increased the BMP of WH by 64% after 210 days of ensiling. The kinetic study showed that the dual‐pool kinetic model described the BMP of ensiled and co‐ensiled WH better than the first‐order and modified Gompertz models.

CONCLUSIONS

Increasing TS and butyric acid contents by co‐ensiling with MS and ES is a low‐cost and sustainable method of enhancing biomethane production from WH. In this way, the invasive nature of WH can be effectively controlled (since a large quantity can be harvested and stored) and circular economy can be enhanced through the effective utilization of waste. © 2022 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).
Age‐Related Changes in the Spatial Variation of Magnetic Susceptibility of Human Articular Cartilage
Authors: Zhang Ming , Liu Chenglei , Lin Huimin , Wang Hanqi , Qin Le , Zhang Zhiyong , Liu Chunlei , Lu Yong , Yan Fuhua , Zhang Yuyao , Wei Hongjiang
Published: November 2022

Background

Quantitative susceptibility mapping (QSM) has shown great potential for revealing the layer structure of articular cartilage based on the laminar susceptibility difference at different depths. However, more information is needed on the effects of age on the spatial distribution of magnetic susceptibility in human cartilage.

Purpose

To assess the ability of QSM to quantify the age‐related differences in depth‐wise cartilage susceptibility values in healthy populations.

Study Type

Prospective.

Population

A total of 94 healthy asymptomatic subjects in three age cohorts: 19–30 (n = 36, 20 males), 31–50 (n = 45, 27 males), and 51–66 years (n = 13, 7 males).

Field Strength/Sequence

3D gradient echo sequences at 3.0 T.

Assessment

Four cartilage compartments were analyzed, including the central lateral/medial femur (cLF/cMF) and the lateral/medial tibia (LT/MT). The spatial susceptibility profile and the corresponding 95% confidence interval (CI) of each age cohort were obtained as functions of the normalized distance from the bone–cartilage interface to the cartilage surface (cartilage depth from 0.0 to 1.0).

Statistical Tests

The relationship between age and cartilage thickness of each cartilage subregion was tested by Pearson correlation with P < 0.05 considered significant. Cartilage depths with separations of 95% CIs were considered to have significant susceptibility differences between two age cohorts with a Bonferroni‐corrected P < 0.05.

Results

The cartilage thickness did not change significantly with age (P value range: 0.06–0.85). Susceptibilities were significantly higher in the 51–66‐year‐olds compared with the 31–50‐year‐olds in the deep layer of cMF (cartilage depth: 0.0–0.22) and LT (0.05–0.28). Susceptibilities were significantly higher in the 51–66‐year‐olds compared with the 19–30‐year‐olds near the cartilage–bone interface of cMF (0.0–0.34), cLF (0.0–0.28), and LT (0.0–0.58). There were also significantly higher susceptibilities in the 31–50‐year‐olds compared with the 19–30‐year‐olds in the deeper regions of cMF (0.26–0.57), cLF (0.0–0.40), and LT (0.07–0.80).

Data Conclusion

Age‐related susceptibility changes in the deeper regions of knee cartilage were observed using QSM.

Evidence Level

2

Technical Efficacy

Stage 2
Biofilm formation, its removal, and consequent effect on the osteoblast response to titanium surfaces: A model for re‐osseointegration
Authors: Chackartchi Tali , Zaydel Liana , Shapira Lior , Shany‐Kdoshim Sharon , Polak David
Published: November 2022

Background

The aim of the study was to characterize pathogenic biofilm formation on titanium surfaces, the ability to remove the biofilm and the osteoblast response to infected and cleaned titanium surfaces as a model for re‐osseointegration.

Methods

Multispecies biofilm composed of Pseudomonas. gingivalis, F. nucleatum, S. sanguis, and A. naeslundii were grown on smooth, acid‐etched, and acid‐etched‐aluminum‐sprayed titanium surfaces. Bacterial viability was determined with live/dead staining. The biofilm was removed mechanically or together with adjunctive antibiotics. The osteoblast (Saos2) response to previously infected, treated and non‐infected titanium surfaces were measured according to 4′‐6‐diamidino‐2‐phenylindole staining. Alkaline phosphatase levels and receptor activator of nuclear factor kappa‐Β ligand/osteoprotegerin expression were measured with enzyme‐linked immunosorbent assay and immunofluorescence staining, respectively The inflammatory environment was established by using differentiated HL‐60 cells (neutrophils) pre‐inoculated onto the biofilm clusters that were more prominent and less scattered on infected titanium surfaces before osteoblast attachment.

Results

Biofilm formed on all the tested surfaces, with an increased thickness on rough surfaces and no differences in bacterial viability. All the treatments reduced the amount of biofilm, but none led to bacteria‐free surfaces. The treated surfaces showed reduced osteoblast attachment and reduced alkaline phosphatase activity compared with non‐infected surfaces. Additionally, treated surfaces showed an osteoblast shift to a pro‐osteoclastic‐induction phenotype, compared with non‐infected surfaces. The presence of experimental inflammation before osteoblast attachment reduced the levels of osteoblast attachment compared with that of the non‐inflamed control.

Conclusions

Biofilm removal from titanium surfaces is incomplete when hand instruments are used alone or in combination with antibiotics. The treated surfaces showed impaired osteoblast attachment and function, particularly in the presence of inflammation, which may prevent or decrease the ability for re‐osseointegration.
Validating biologic age in selecting elderly patients with pancreatic cancer for surgical resection
Authors: Scholer Anthony J. , Marcus Rebecca , Garland‐Kledzik Mary , Chang Shu‐Chin , Khader Adam , Santamaria‐Barria Juan , Jutric Zeljka , Wolf Ronald , Goldfarb Melanie
Published: November 2022

Background and Objectives

Selecting frail elderly patients with pancreatic cancer (PC) for pancreas resection using biologic age has not been elucidated. This study determined the feasibility of the deficit accumulation frailty index (DAFI) in identifying such patients and its association with surgical outcomes.

Methods

The DAFI, which assesses frailty based on biologic age, was used to identify frail patients using clinical and health‐related quality‐of‐life data. The characteristics of frail and nonfrail patients were compared.

Results

Of 242 patients (median age, 75.5 years), 61.2% were frail and 32.6% had undergone pancreas resection (surgery group). Median overall survival (mOS) decreased in frail patients (7.13 months, 95% confidence interval [CI]: 5.65–10.1) compared with nonfrail patients (16.1 months, 95% CI: 11.47–34.40, p = 0.001). In the surgery group, mOS improved in the nonfrail patients (49.4%; 49.2 months, 95% CI: 29.3–79.9) compared with frail patients (50.6%, 22.1 months, 95% CI: 18.3–52.4, p = 0.10). In the no‐surgery group, mOS was better in nonfrail patients (54%; 10.81 months, CI 7.85–16.03) compared with frail patients (66%; 5.45 months, 95% CI: 4.34–7.03, p = 0.02).

Conclusions

The DAFI identified elderly patients with PC at risk of poor outcomes and can identify patients who can tolerate more aggressive treatments.
Slow twitch paraspinal muscle dysregulation in adolescent idiopathic scoliosis exhibiting HIF‐2α misexpression
Authors: Tam Wai Kit , Cheung Jason P. Y. , Koljonen Paul A. , Kwan Kenny Y. H. , Cheung Kenneth M.C. , Leung Victor Y. L.
Published: November 2022

Background

Adolescent idiopathic scoliosis (AIS) refers to a three‐dimensional spinal deformity which has a typical onset during adolescence. In most cases, the cause of the deformity cannot be clearly identified. Unbalanced paraspinal muscle activity in AIS patients was reported and hypoxia was implicated to regulate myogenesis. This study aims to investigate the association between myogenesis/muscle toning and HIF‐αs activity in the pathogenesis of AIS.

Methods

HIF‐αs expression was examined by enzyme‐linked immunosorbent assay and western blot in paraspinal myoblasts isolated from 18 subjects who underwent deformity correction surgery. QPCR was conducted to measure the gene expression levels of perinatal muscle fiber markers MYH3, MYH8; slow twitch muscle fiber markers MHY7; fast twitch muscle fiber markers MYH4; and myogenic regulatory factors MYF5 and MYOG. Slow and fast twitch muscle fiber composition in concave/convex paraspinal musculature of AIS subjects was evaluated by immunostaining of myosin heavy chain type I (MyHC I) and myosin heavy chain type II (MyHC II).

Results

Reduced HIF‐2α induction under hypoxia was found in paraspinal myoblast culture of 33% AIS subjects. We detected a suppression of perinatal and slow twitch muscle fiber associated genes, but not fast twitch muscle fiber‐associated genes and myogenic regulatory factors in HIF‐2α misexpressed AIS myoblasts. Distinct reduction of slow twitch muscle fiber was evidenced in convex paraspinal musculature, suggesting an asymmetric expression of slow twitch muscle fiber in HIF‐2α misexpressed AIS patients.

Conclusions

This study indicates an association of abnormal HIF‐2α expression in paraspinal myoblasts and a disproportionate slow twitch muscle fiber content in the convexity of the curvature in a subset of AIS subjects, suggesting HIF‐2α dysregulation as a possible risk factor for AIS. The role of HIF‐2α in paraspinal muscle function during spinal growth and its relevance in AIS prognosis warrants further investigation.
Posttraumatic growth related to the COVID‐19 pandemic among individuals with lived experience of psychiatric disorder
Authors: Lewis Catrin , Lewis Katie , Edwards Bethan , Evison Claudia , John Ann , Pearce Holly , Raisanen Lawrence , Richards Natalie , Roberts Alice , Jones Ian , Bisson Jonathan I.
Published: November 2022

Although the COVID‐19 pandemic has been shown to be detrimental to mental health, it may hold a parallel potential for positive change. Little is known about posttraumatic growth (PTG) as a potential outcome for individuals with lived experience of psychiatric disorders following trauma exposure, especially in the context of the COVID‐19 pandemic. Participants were 1,424 adults with lived experience of a psychiatric disorder who took part in a longitudinal study of mental health during the COVID‐19 pandemic conducted by the National Centre for Mental Health. PTG was measured using the Posttraumatic Growth Inventory–Short Form (PTGI‐SF). Factors hypothesized to be associated with PTG were investigated using linear regression. The mean participant PTGI score was 12.64 (SD = 11.01). On average, participants reported the highest scores on items related to appreciation of life and lowest on those related to spiritual change subscale. We found the strongest evidence of associations between higher levels of PTG and higher scores on assessment items related to perceived social support, B = 2.86; perceptions of the pandemic as traumatic, B = 4.89; and higher psychological well‐being, B = 0.40. Taken together, we did not observe evidence of widespread PTG related to the COVID‐19 pandemic among individuals with lived experiences of psychiatric disorders.
Hurdles of innovation—insights from a new healthcare delivery innovation program
Authors: Bardach Shoshana , Perry Amanda , Powell Lillian , Kapadia Nirav , Barnato Amber
Published: November 2022

Introduction

Healthcare systems are actively working to innovate their care delivery models, seeking to improve service quality, improve patient and provider satisfaction, and reduce cost.

Methods

By critically evaluating our experiences to date, this article highlights challenges systems may face in the process of trying to redesign healthcare and offers insights on how to navigate hurdles. We identify barriers to—and ultimately approaches to promote—rapid, scalable, sustainable, and transformative care redesign.

Results

Dedicated electronic health record IT and analytic support, and ongoing leadership engagement and communication, play a valuable role in enabling redesign efforts. Flexible, but guided, innovation support helps teams stay accountable and motivated, while accommodating new project needs and directions. Understanding the change ecosystem and evaluating and sharing outcomes on an ongoing basis, enables teams to adapt as needed. Facilitation and support help realize the value of diverse, engaged teams; novel approaches and techniques draw out innovative perspectives and promote creative thinking.

Conclusions

Although not an exhaustive list of challenges or strategies to overcome them, we hope these insights will contribute to a culture of innovation and support other institutions in their healthcare redesign initiatives.