bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of 5α-Reductase Inhibitors With Prostate Cancer Mortality
Authors: Björnebo Lars , Nordström Tobias , Discacciati Andrea , Palsdottir Thorgerdur , Aly Markus , Grönberg Henrik , Eklund Martin , Lantz Anna
Published: May 2022

Importance

There is evidence that 5α-reductase inhibitors (5-ARIs), a standard treatment of benign prostate hyperplasia, are associated with a decrease in the incidence of prostate cancer (PCa). However, studies to date have had conflicting results regarding the association with prostate cancer mortality (PCM).

Objective

To evaluate the association of treatment with 5-ARIs with PCM in men without a prior diagnosis of PCa.

Design, Setting, and Participants

This population-based cohort study was conducted in Stockholm, Sweden, between January 1, 2007, and December 31, 2018, and included 429 977 men with a prostate-specific antigen (PSA) test within the study period. Study entry was set to 1 year after the first PSA test. Data were analyzed from September 2021 to December 2021.

Exposures

After their initial PSA test, men with 2 or more newly dispensed prescriptions of 5-ARI, finasteride, or dutasteride were considered 5-ARI users (n = 26 190).

Main Outcomes and Measures

Primary outcome was PCM. Cox proportional hazards regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% CIs for all-cause mortality and PCM.

Results

The study cohort included 349 152 men. The median (IQR) age for those with 2 or more filled prescriptions of 5-ARI was 66 (61-73) years and 57 (50-64) years for those without. The median follow-up time was 8.2 (IQR, 4.9-10) years with 2 257 619 person-years for the unexposed group and 124 008 person-years for the exposed group. The median exposure to treatment with 5-ARI was 4.5 (IQR, 2.1-7.4) years. During follow-up, 35 767 men (8.3%) died, with 852 deaths associated with PCa. The adjusted multivariable survival analysis showed a lower risk of PCM in the 5-ARI group with longer exposure times (0.1-2.0 years: adjusted HR, 0.89; 95% CI, 0.64-1.25; >8 years: adjusted HR, 0.44; 95% CI, 0.27-0.74). No statistically significant differences were seen in all-cause mortality between the exposed and unexposed group. Men treated with 5-ARIs underwent more PSA tests and biopsies per year than the unexposed group (median of 0.63 vs 0.33 and 0.22 vs 0.12, respectively).

Conclusions and Relevance

The results of this cohort study suggest that there was no association between treatment with 5-ARI and increased PCM in a large population-based cohort of men without a previous PCa diagnosis. Additionally, a time-dependent association was seen with decreased risk of PCM with longer 5-ARI treatment. Further research is needed to determine whether the differences are because of intrinsic drug effects or PCa testing differences.
Suggestions for new organizational-level item pools for the national Stress Check Program from management philosophy and mission statement: A qualitative study using unsupervised learning
Authors: Watanabe Kazuhiro , Inoue Akiomi , Eguchi Hisashi , Iwata Noboru , Odagiri Yuko , Tsutsumi Akizumi
Published: May 2022

Objective

This study aimed to obtain suggestions for new organizational-level item pools that companies could utilize to accomplish management philosophy and mission statements in the context of survey and work environment improvements for the national Stress Check Program.

Methods

A qualitative study was conducted using unsupervised learning. A large amount of text data related to management philosophy and mission statements were collected, that is, management messages described on the websites of all companies listed on the Tokyo Stock Exchange. For the main analysis, topic modeling was performed on the nouns from the management messages using Latent Dirichlet Allocation (LDA) to build a model consisting of 10 latent topics, each represented by a group of the 10 most frequently reoccurring nouns. Each group of nouns was qualitatively summarized based on the topic model.

Results

In total, 22 524 nouns were extracted from the management messages of 3575 companies. A topic model consisting of 10 latent topics was constructed using the LDA. The suggestion for new item pools included new technologies, business plans/strategies, company shareholders, health/happiness/wealth, profits/sales, development of society, a sustainable society, safety and security, customer/consumer satisfaction, corporate social responsibility, fairness, transparency, and human rights.

Conclusion

The suggestions for potential item pools were derived from management philosophy and mission statement that are not covered in the existing survey. The suggestions could be useful for motivating employers to implement work environment improvement. Future studies need to make definite items and investigate whether they correlate to job stressors and mental health among workers.
Factors Influencing Pain Response Following Patient Education and Supervised Exercise in Male and Female Subjects With Hip Osteoarthritis
Authors: Perruccio Anthony V. , Roos Ewa M. , Skou Søren T. , Grønne Dorte T. , Davis Aileen M.
Published: May 2022

Objective

To understand factors associated with pain intensity responder status following nonsurgical hip osteoarthritis (OA) intervention, according to sex.

Methods

Data were from individuals with hip OA participating in the Danish Good Life With Osteoarthritis in Denmark 8‐week education and exercise program. The following factors were recorded at program entry: age; education; mental well‐being; comorbidities; body mass index; symptoms in hip, knee, and low back; and program‐specific factors including education sessions, former participant lectures, and supervised exercise sessions. Pain intensity was recorded at baseline and at month 3 (post‐program) on a 0–100‐mm visual analog scale. Response was defined as pain intensity improvement of ≥30% from baseline to post‐program. Logistic regression was used and conducted separately in male and female subjects.

Results

The sample included 791 men and 2,253 women. Female subjects had a mean baseline pain score of 47.2 of 100 (95% confidence interval [95% CI] 46.4–48.1) and male subjects had a score of 41.7 (95% CI 40.3–43.1). By post‐program, the proportion of pain responders was 50.4% among women and 45.8% among men (difference P = 0.025). Among women, program‐specific factors (attending former participant lectures and more supervised exercise sessions) were positively associated with pain response, as were better mental well‐being and fewer comorbidities, while symptoms in other joints/sites were associated with a decreased likelihood of response. Among men, program‐specific factors were not associated with response, while better mental well‐being and fewer comorbidities were associated with being a responder.

Conclusion

Findings suggest that the influence of some factors on pain response differ for male and female subjects and point to a potential need for targeted approaches for men and women who may require different key messages/approaches from health care providers.
Bone Marrow Lesions and Magnetic Resonance Imaging–Detected Structural Abnormalities in Patients With Midfoot Pain and Osteoarthritis: A Cross‐Sectional Study
Authors: Arnold John B. , Halstead Jill , Martín‐Hervás Carmen , Grainger Andrew J. , Keenan Anne‐Maree , Hill Catherine L. , Conaghan Philip G. , McGonagle Dennis , Redmond Anthony C.
Published: May 2022

Objective

To compare magnetic resonance imaging (MRI)–detected structural abnormalities in patients with symptomatic midfoot osteoarthritis (OA), patients with persistent midfoot pain, and asymptomatic controls, and to explore the association between MRI features, pain, and foot‐related disability.

Methods

One hundred seven adults consisting of 50 patients with symptomatic and radiographically confirmed midfoot OA, 22 adults with persistent midfoot pain but absence of radiographic OA, and 35 asymptomatic adults underwent 3T MRI of the midfoot and clinical assessment. MRIs were read for the presence and severity of abnormalities (bone marrow lesions [BMLs], subchondral cysts, osteophytes, joint space narrowing [JSN], effusion‐synovitis, tenosynovitis, and enthesopathy) using the Foot Osteoarthritis MRI Score. Pain and foot‐related disability were assessed with the Manchester Foot Pain and Disability Index.

Results

The severity sum score of BMLs in the midfoot was greater in patients with midfoot pain and no signs of OA on radiography compared to controls (P = 0.007), with a pattern of involvement in the cuneiform–metatarsal joints similar to that in patients with midfoot OA. In univariable models, BMLs (ρ = 0.307), JSN (ρ = 0.423), and subchondral cysts (ρ = 0.302) were positively associated with pain (P < 0.01). In multivariable models, MRI abnormalities were not associated with pain and disability when adjusted for covariates.

Conclusion

In individuals with persistent midfoot pain but no signs of OA on radiography, MRI findings suggested an underrecognized prevalence of OA, particularly in the second and third cuneiform–metatarsal joints, where BML patterns were consistent with previously recognized sites of elevated mechanical loading. Joint abnormalities were not strongly associated with pain or foot‐related disability.
Noncontact Human–Machine Interface Using Complementary Information Fusion Based on MEMS and Triboelectric Sensors
Authors: Le Xianhao , Shi Qiongfeng , Sun Zhongda , Xie Jin , Lee Chengkuo
Published: May 2022

Current noncontact human–machine interfaces (HMIs) either suffer from high power consumption, complex signal processing circuits, and algorithms, or cannot support multidimensional interaction. Here, a minimalist, low‐power, and multimodal noncontact interaction interface is realized by fusing the complementary information obtained from a microelectromechanical system (MEMS) humidity sensor and a triboelectric sensor. The humidity sensor composed of a two‐port aluminum nitride (AlN) bulk wave resonator operating in its length extensional mode and a layer of graphene oxide (GO) film with uniform and controllable thickness, possesses an ultra‐tiny form factor (200 × 400 µm2), high signal strength (Q = 1729.5), and low signal noise level (±0.31%RH), and is able to continuously and steadily interact with an approaching finger. Meanwhile, the facile triboelectric sensor made of two annular aluminum electrodes enables the interaction interface to rapidly recognize the multidirectional finger movements. By leveraging the resonant frequency changes of the humidity sensor and output voltage waveforms of the triboelectric sensor, the proposed interaction interface is successfully demonstrated as a game control interface to manipulate a car in virtual reality (VR) space and a password input interface to enter high‐security 3D passwords, indicating its great potential in diversified applications in the future Metaverse.
Unconventional Highly Active and Stable Oxygen Reduction Catalysts Informed by Computational Design Strategies
Authors: Jacobs Ryan , Liu Jian , Na Beom Tak , Guan Bo , Yang Tao , Lee Shiwoo , Hackett Greg , Kalapos Tom , Abernathy Harry , Morgan Dane
Published: May 2022

Discovering and engineering new materials with fast oxygen surface exchange kinetics and robust long‐term stability is essential for the large‐scale, economically viable commercialization of solid oxide fuel cell (SOFC) technology. The perovskite catalyst material BaFe0.125Co0.125Zr0.75O3 (BFCZ75), predicted to be promising from recent density functional theory (DFT) calculations and unconventional due to its extremely high Zr content and low electronic conductivity, exhibits oxygen reduction reaction surface exchange rates on par with Ba0.5Sr0.5Co0.8Fe0.2O3 (BSCF) and excellent stability at typical operating temperatures. New composite electrodes are engineered by integrating BFCZ75 with commercial electrode materials La1–xSrxMnO3 (LSM) and La1–xSrxCoyFe1–yO3 (LSCF) and achieve high performance as measured by low area specific resistance (ASR) values, with the LSCF/BFCZ75 ASR values comparable to top performing noncomposite electrode materials such as SrCo0.8Sc0.2O3–δ, BaNb0.05Fe0.95O3–δ and BaCo0.7Fe0.22Y0.08O3–δ. The use of BFCZ75 as a composite with LSCF achieving low ASR values shows that BFCZ75 is highly active and can easily integrate into existing SOFC material supply chains, lowering the barrier for potential commercial application of new electrode materials. Finally, these findings point to a broader unexplored class of perovskite materials with high fractions of redox inactive species (e.g., Zr, Nb, and Ta) that may unlock new pathways to realizing improved commercial SOFCs.
Location, production systems, and processing method effects on qualities of Kafa Biosphere Reserve coffees
Authors: Tassew Addis Alemayehu , Yadessa Gezahegn Berecha , Bote Adugna Debela , Obso Taye Kufa
Published: May 2022

A comprehensive physical and cup quality assessment of coffee (Coffea arabica L.) has not yet been conducted on Kafa Biosphere Reserve coffees. Hence, the influence of location, production systems, and processing methods on coffee bean physical and sensorial qualities were studied to identify the inherent qualities and suitable preparation methods for the improvement of bean physical and organoleptic qualities. In a three‐stage nested design, factors such as location (Gimbo, Gawata, and Decha districts), coffee production system (forest, semiforest, and garden), and processing method (wet, semiwet, and dry) were considered. Preliminary coffee quality assessment data were gathered from bean physical and cup quality analyses of coffee obtained from the combination of the three factors. An ANOVA was conducted on preliminary coffee quality data. The result of the ANOVA showed that location and production system effects were significant only on bean moisture content (P < .01) and acidity (P < .05), respectively. The processing effect had a significant effect on bean moisture (P < .01), odor (P < .001), raw (P < .01), and preliminary grade (P < .05). Better coffee quality was maintained in the dry coffee processing method within the recommended moisture content. Forest and semiforest coffees respond poorly in odor and overall raw coffee quality when treated with wet and semiwet processing methods. Hence, to attain a better quality of coffee, rather than proper harvesting procedures, more emphasis should be given to choosing proper processing methods. Further investigation that includes the effects of elevation gradient is recommended.
Improvement of under‐the‐rib oxygen concentration and water removal in proton exchange membrane fuel cells through three‐dimensional metal printed novel flow fields
Authors: Chen Gaojian , Shi Weidong , Xuan Jin , Penga Željko , Xu Qian , Guo Hang , Su Huaneng , Xing Lei
Published: May 2022

The porous electrode under the rib area suffers from lower local oxygen concentration and more severe water flooding than that under the channel, which significantly affect the performance of proton exchange membrane fuel cells. To improve the oxygen concentration and water drainage under the rib, a series of novel flow fields with auxiliary channels equipped with through‐plane arrayed holes were manufactured by three‐dimensional (3D) metal printing, and the cell performance, ohmic resistance and pressure drop were experimentally and numerically studied, respectively. The novel fields were based on the sophisticated modification of traditional serpentine and parallel flow fields, that significantly improved the cell performance at high current density with an optimal number or length of the auxiliary channels, owing to the trade‐off between the electric resistance and mass transfer under the rib. This novel flow field design solved the trilemma of performance, pressure drop and manufacture feasibility through the implementation of 3D printing technology.
One‐For‐All Polyolefin Functionalization: Active Ester as Gateway to Combine Insertion Polymerization with ROP, NMP, and RAFT
Authors: Dau Huong , Tsogtgerel Enkhjargal , Matyjaszewski Krzysztof , Harth Eva
Published: May 2022

This work develops the Polyolefin Active‐Ester Exchange (PACE) process to afford well‐defined polyolefin–polyvinyl block copolymers. α‐Diimine PdII‐catalyzed olefin polymerizations were investigated through in‐depth kinetic studies in comparison to an analog to establish the critical design that facilitates catalyst activation. Simple transformations lead to a diversity of functional groups forming polyolefin macroinitiators or macro‐mediators for various subsequent controlled polymerization techniques. Preparation of block copolymers with different architectures, molecular weights, and compositions was demonstrated with ring‐opening polymerization (ROP), nitroxide‐mediated polymerization (NMP), and photoiniferter reversible addition–fragmentation chain transfer (PI‐RAFT). The significant difference in the properties of polyolefin–polyacrylamide block copolymers was harnessed to carry out polymerization‐induced self‐assembly (PISA) and study the nanostructure behaviors.
Narrative Practices for Children with ASD: Hey! My Therapist Has an Imaginary Friend and Other Anti‐tantrum Practices*
Authors: Chimpén‐López Carlos Alexis , Andrés‐Gárriz Clara , Pretel‐Luque Teresa
Published: May 2022

Aggressive behaviour is one of the most disruptive problems in children with autism. It generates anxiety in the parents and the child, who does not know what to do, and the family's quality of life is significantly reduced. In this scenario, using narrative practices may help promote the sense of agency in children with autism spectrum disorder (ASD) and help them find solutions based on self‐knowledge. This article explores different narrative practices to help deal with challenging behaviour in children with ASD. We discuss several examples using two techniques: a therapist's imaginary friend and using a magic coin as ways of externalising the problem and playing with metaphors. We present the procedures applied during the interventions with three children. These narrative practices can help to externalise the problem, think about possible solutions, and facilitate the development of imagination and abstract thinking in children with ASD.
The low dielectric constant hyperbranched polycarbosilane derived resins with spacing groups
Authors: Long Quan , Li Xia , Huang Yawen , Peng Qiuxia , Li Xian , Zhu Liangbo , Ma Jiajun , Ye Xu , Yang Junxiao
Published: May 2022

The route via the cross‐linking of hyperbranched prepolymers has potential advantage to construct low dielectric constant (low‐k) resins owing to the enhanced molecular free volume in hyperbranched structure. However, it is still a challenge to prepare hyperbranched resins with good film‐forming property and low‐k. In this paper, two hyperbranched polycarbosilanes with reactive benzocyclobutene groups were synthesized via hydrosilylation reaction to avoid the generation of SiO bonds for enabling the low polarity of chemical bonds. The spacing groups including phenyl or ethylene were incorporated into the hyperbranched structures, and the effect of the spacing groups on the physicochemical properties of hyperbranched polycarbosilane derived resins were investigated. The phenyl groups were found to effectively decrease the dielectric constant (k), while endowing the resins with good film forming ability and thermostability. The UV/thermally cured phenyl group resin owing to dual crosslinked structure, the patterns would not be deformed significantly during thermally cured process. Both hyperbranched polycarbosilane derived resins could be potential photoresists.
Effect of chain extenders on the hydrolytic degradation of soybean polyurethane
Authors: Favero Diana , Marcon Victória , Agnol Lucas Dall , Gómez Clara M. , Cros Ana , Garro Nuria , Sanchis Maria J. , Carsí Marta , Figueroa Carlos A. , Bianchi Otávio
Published: May 2022

This publication highlights the effect that different chain extenders (CEs) have on the structure–property relationships of soy‐based polyurethanes that have been exposed to hydrolytic degradation for 480 and 960 h at 80°C. Gel content, crosslinking densities, surface energy, atomic force microscopy, dielectric, and dynamic mechanics were used for monitored structural changes. Polyurethanes (PU) is composed of a structure with minor phase separation when a chain extender is not used, maintaining all properties over time. However, when a chain extender, butane‐1.4‐diol (BDO), ethane‐1.2‐diol (MEG) our (2‐hydroxypropoxy)‐propane‐2‐ol are added, it is noted that there is a more significant degradation in the flexible domains, modifying the fraction between the initial rigid (HS)/soft (SS) segment that makes the polymer stiff and brittle. The hydrolysis degradation generates new Fourier transform infrared bands relative to urea (1640 cm−1) and amide (1800 cm−1). The reduction in band intensity of the C=Ofree at 1730 cm−1, while increasing the intensity of C=Obonded at 1710 cm−1 indicated a higher phase separation degree. After 960 h the TgS decreased, while the TgH was practically unchanged. The higher polarization observed in the PUs with BDO and MEG samples indicates the increased phase separation resulting in hydrolytic degradation.
Multiagent coverage search based on Voronoi and sparse heteroscedastic Gaussian process
Authors: Xu Xiaoling , Meng Wei , Cai Qianqian , Fu Minyue
Published: May 2022

This work is concerned with multiagent cooperative and autonomous coverage search in an unknown environment. A novel Voronoi and sparse heteroscedastic Gaussian process (SHGP)‐based search method is proposed to improve the target search efficiency. By means of heteroscedastic Gaussian process (HGP), each agent can estimate the probability of target existence in given locations online according to the local probability map. Then, these local probability maps are fused together to obtain a posterior probability distribution for target prediction. Based on that, the agents' search paths within Voronoi cells will be adjusted adaptively online to make sure all the agents can search for targets more efficiently. A challenging issue then falls in the computational complexity of the HGP. To solve this problem, we propose an adaptive ranked‐set sampling algorithm based on the weighted sampling process and K‐means clustering algorithm. Theoretical analysis on the discrepancy of the kernel matrix between the original probability points and the sampling points is also given. Simulation results demonstrate that our proposed coverage search method can improve the performance of the area search compared with the existing Voronoi‐based one.
Increased prefrontal GABA concentrations in adults with autism spectrum disorders
Authors: Maier Simon , Düppers Ansgard Lena , Runge Kimon , Dacko Michael , Lange Thomas , Fangmeier Thomas , Riedel Andreas , Ebert Dieter , Endres Dominique , Domschke Katharina , Perlov Evgeniy , Nickel Kathrin , Tebartz van Elst Ludger
Published: May 2022

The excitatory‐inhibitory imbalance hypothesis postulates dysregulation of the gamma‐aminobutyric acid (GABA) and glutamate (Glu) neurotransmitter systems as a common underlying deficit in individuals with autism spectrum disorders (ASD). Previous studies suggest an important role of these systems in the pathophysiology of ASD, including a study of our group reporting decreased glutamate concentrations in the pregenual anterior cingulate cortex (ACC) of adults with ASD. The aim of this study was to replicate our previous findings of impaired glutamate metabolism in ASD in a new sample and to additionally quantify GABA in the ACC and dorsolateral prefrontal cortex (dlPFC). Concentrations of GABA and glutamate‐glutamine (Glx; combined glutamate and glutamine signal) were quantified in the ACC and dlPFC of 43 adults with ASD and 43 neurotypical controls (NTC) by magnetic resonance spectroscopy (MRS). The ASD group showed increased absolute GABA concentrations and elevated GABA/creatine ratios in the left dlPFC compared to NTC, while no group differences were detected in the pregenual and dorsal ACC. Previous findings of altered Glx concentration in the pregenual ACC of the ASD group could not be replicated. Regarding Glx concentrations and Glx/creatine ratios, there were no significant differences in the dlPFC and ACC either. The study supports the hypothesis of an altered GABA and glutamate equilibrium, indicating an imbalance between excitatory and inhibitory metabolism in ASD patients. However, inconsistent results across studies and brain regions suggest a complex underlying phenomenon.

Lay Summary

Adults of the autism spectrum exhibit elevated levels of the inhibitory neurotransmitter GABA in the left dorsolateral prefrontal cortex.

This finding supports the hypothesis of an imbalance between excitatory and inhibitory equilibrium in patients with autism spectrum disorders.
Therapy outcome of day treatment for people with anorexia nervosa before and during the COVID‐19 pandemic
Authors: Carr Anna , Toloza Cindy , Li Zhuo , Nazar Bruno Palazzo , Himmerich Hubertus
Published: May 2022

Objective: The current research aimed to compare clinical outcome measures of two National Eating Disorder (ED) Day Services at the Maudsley Hospital from before the COVID‐19 lockdown, when treatment was face to face, with after the lockdown when treatment moved online.

Method: Clinical outcome measures collected as part of the admission and discharge process were compared from the beginning and end of treatment for patients treated either via face‐to‐face or online delivery. Twenty‐nine patients’ data were analyzed (89% of them female, 11% male, 89% from White ethnic backgrounds, 11% from BAME ethnic backgrounds and a mean age of 25.99 years). Additionally, the mean change in outcome measures was also compared between the two groups (pre‐lockdown face to face and during lockdown online).

Results: Treatment delivered face to face led to significant improvements in body mass index (BMI) but not in Eating Disorder Examination Questionnaire (EDEQ) Global and Work and Social Adjustment Scale (WSAS) Total scores. In contrast, treatment delivered online led to significant improvements in EDEQ Global and WSAS Total scores but not in BMI. Neither one of the delivery modalities created significantly larger mean changes in any of the clinical outcome measures than the other.

Conclusions: Both face‐to‐face and online delivery of eating disorder day treatment show some success. Suggested improvements for using online delivery of treatment include implementing additional support opportunities, adapting the online format to improve communication and commitment and using a hybrid model of specific face‐to‐face elements with some online treatment.
Expression of CD226 is upregulated on Tr1 cells from neuromyelitis optica spectrum disorder patients
Authors: Chen Ping , Wu Mingmei , Wang Ning , Xia Feng , Du Fang , Liu Zhirong , Wang Jinchun , Jin Jingyi , Jin Boquan , Zhao Gang , Chen Lihua , Yi Jing , Fang Liang
Published: May 2022

Background

Neuromyelitis optica spectrum disorder (NMOSD) is a central and acute demyelinating disease of the central nervous system with unusual clinical course. The development of novel biomarkers for NMOSD is critical for implementing effective clinical treatment. CD226 is known to be expressed on many types of peripheral lymphoid cells. However, the expression level and function of CD226 on type 1 T regulatory (Tr1) cells during NMOSD is unknown.

Methods

Eighteen patients with NMOSD and 10 healthy volunteers were enrolled in the test group to probe the difference of CD226 expression on Tr1 cells using flow cytometric analysis.

Results

The expression of CD226 on Tr1 cells exhibited significantly increased tendency in NMOSD patients. Additionally, methylprednisolone and rituximab treatment decreased the expression of CD226 on Tr1 cells. Furthermore, the expression of CD226 on Tr1 cells was correlated with disease severity.

Conclusion

This study provides a new basic insight into CD226 expression pattern on Tr1 cells, which have great potential to be biomarkers for monitoring the development and treatment of NMOSD.
Molecular landscape and therapeutic alterations in Asian soft‐tissue sarcoma patients
Authors: Gan Meifu , Zhang Chen , Qiu Liqing , Wang Yue , Bao Hua , Yu Ruoying , Liu Rui , Wu Xue , Shao Yang , Hou Peifeng , Fei Zhenglei
Published: May 2022

Background

Soft‐tissue sarcoma (STS) is a rare solid malignant tumor with numerous histologic subtypes. Current studies on targeted therapy for STS are in preclinical and early‐phase trials. Genomic differences largely influence the prognosis of patients even with the same subtype. To investigate the genomic alterations (GAs) and the potential of targeted therapy in STS, we analyzed the genomic landscape, the therapeutic GAs, and biomarkers of immunotherapy in Chinese STS patients.

Methods

Targeted sequencing covering 425 genes was performed, from which we obtained the results of tissue samples from 351 Chinese STS patients of all ages covering different histologic subtypes. Bioinformatics analysis of altered genes with nonsynonymous mutations, copy‐number variations, and gene fusions were performed. OncoKB therapeutic GAs and relevant biomarkers including TMB, MSI, and HRD were further examined for potential targeted therapy.

Results

In total, 2743 GAs were identified in 330 genes with a median of 6 (1–38) per case. The top 11 frequently altered genes were: TP53, MCL1, MDM2, CDK4, MYC, CDKN2A, GNAS, RB1, ATRX, CDKN2B, and FGFR1. OncoKB defined therapeutic GAs were found in 23 genes in 43% of the patients. In general, 9.4% of the patients had high‐TMB, 2.8% had MSI, and 13.7% had HRD. A significant difference in the percentage of patients with OncoKB therapeutic GAs were observed between the most frequent two subtypes, leiomyosarcoma and liposarcoma. Altogether, 54% of the patients had the potential to respond to a targeted therapy.

Conclusion

This study indicated the potential efficacy of targeted therapy on many STS patients, and also provided insight for novel precision therapy. The clinical efficacy of combining targeted therapy and immunotherapy can be further investigated.
Minimal residual disease assessment of papillary thyroid carcinoma through circulating tumor cell‐based cytology
Authors: Innaro Nadia , Gervasi Rita , Ferrazzo Teresa , Garo Nastassia C. , Curto Lucia S. , Lavecchia Annamaria , Aquila Isabella , Donato Giuseppe , Malara Natalia
Published: May 2022

The overall estimated risk of recurrence after an apparently complete thyroid cancer resection ranges from <1% to 55%, and the high‐quality pathology report is crucial for proper risk stratification. The neck ultrasound (US) and serum thyroglobulin (Tg) and anti‐Tg antibody (TgAb) assays are the mainstays for Differentiated Thyroid Cancer (DTC) follow‐up. However, the neck US includes a high frequency of nonspecific findings and despite the serum, Tg unmasks the presence of thyrocytes, it is not discriminating between normal and malignant cells. In this study, to improve post‐surgery follow‐up of minimal residual disease in papillary thyroid cancer (PTC) patients, blood‐derived cytology specimens were evaluated for the presence of circulating tumor cells (CTCs). The presence of CTCs of thyroid origin was confirmed by cytomorphological and tissue‐specific antigens analysis (Thyroid Transcription Factor‐1/TTF‐1 and Tg) and proliferative profile (percentage of cells in S‐phase). Our data revealed an unfavorable’ prognostic risk in patients with >5% CTCs (p = 0.09) and with >30% S‐phase cells at baseline (p = 0.0015), predicting ≤1 year relapsing lesion event. These results suggest a new intriguing frontier of precision oncology forefront cytology‐based liquid biopsy.
Nitrogen Disturbance Awakening the Intrinsic Activity of Nickel Phosphide for Boosted Hydrogen Evolution Reaction
Authors: Yang Caixia , Wang Zhiqiang , Li Zhendong , Pan Yichen , Jiang Linwei , Li Caicai , Wang Chao , Sun Qingfeng
Published: May 2022

Nickel phosphide (Ni2P) has emerged as a promising candidate to substitute Pt‐based catalysts for hydrogen evolution reaction (HER) due to the hydrogenase‐like catalytic mechanism and concomitantly low cost. However, its catalytic activity is still not comparable to that of noble‐metal‐based catalysts, and innovative strategies are still urgently needed to further improve its performance. Herein, a self‐supported N‐doped Ni2P on Ni foam (N−Ni2P/NF) was rationally designed and fabricated through a facile NH4H2PO2‐assisted gas‐solid reaction process. As an HER catalyst in alkaline medium, the obtained N−Ni2P/NF revealed excellent electrocatalytic performance with a distinctly low overpotential of 50 mV at 10 mA cm−2, a small Tafel slope of 45 mV dec−1, and long‐term stability for 25 h. In addition, the spectroscopic characterizations and density functional theory calculations confirmed that the incorporation of N regulated the original electronic structure of Ni2P, enhanced its intrinsic catalytic property, optimized the Gibbs free energy of reaction intermediates, and ultimately promoted the HER process. This work provides an atomic‐level insight into the electronic structure modulation of metal phosphides and opens an avenue for developing advanced transition metal phosphides‐based catalysts.
Association of alcohol drinking with incident type 2 diabetes and pre‐diabetes: The Guangzhou Biobank Cohort Study
Authors: Li Mei Jiao , Ren Jing , Zhang Wei Sen , Jiang Chao Qiang , Jin Ya Li , Lam Tai Hing , Cheng Kar Keung , Thomas G. Neil , Xu Lin
Published: May 2022

Aims

We examined associations of baseline alcohol drinking with incident type 2 diabetes (T2D) or impaired fasting glucose (IFG), and explore whether the associations were modified by genetic polymorphisms of aldehyde dehydrogenase‐2 (ALDH2) and alcohol dehydrogenase‐1B (ADH1B).

Materials and methods

All participants were aged 50+ (mean = 60.45; standard deviation = 6.88) years. Information of alcohol consumption was collected at baseline from 2003 to 2008. Incident T2D was defined as fasting glucose ≥7.0 mmol/L or post‐load glucose ≥11.1 mmol/L at follow‐up examination (2008–2012), self‐reported T2D and/or initiation of hypoglycaemia medication or insulin during follow‐up. Impaired fasting glucose was defined as fasting glucose ≥5.6 mmol/L and <7 mmol/L.

Results

Of 15,716 participants without diabetes and 11,232 participants without diabetes and IFG at baseline, 1624 (10.33%) developed incident T2D and 1004 (8.94%) developed incident IFG during an average 4 years of follow‐up. After multivariable adjustments, compared with never drinking, occasional or moderate alcohol drinking was not associated with risk of incident hyperglycaemia (T2D + IFG) (odds ratio (OR) = 1.10, 95% confidence interval (CI) 0.95–1.27, and 0.90 (0.69–1.18), respectively), whereas heavy alcohol drinking was associated with a higher risk of incident hyperglycaemia (T2D + IFG) (OR = 1.82, 95% CI 1.24–2.68). No interactions of sex, overweight/obesity and genetic polymorphisms of ADH1B/ALDH2 genes with alcohol drinking on incident T2D and/or IFG were found (P for interaction from 0.12 to 0.85).

Conclusions

Our results support a detrimental effect of heavy alcohol use on IFG and T2D. No protective effect was found for those carrying lower risk alleles for ADH1B/ALDH2 genes.
Whole plant traits of coastal dune vegetation and implications for interactions with dune dynamics
Authors: Walker Shannon L. , Zinnert Julie
Published: May 2022

Coastal dunes are important protective features against sea level rise and coastal storms. Interactions between dune plant aboveground structures and sediment trapping that allow for dune building and maintenance are well established. More recently, studies documenting belowground biomass for promoting erosion resistance in dominant dune species have been conducted, yet a knowledge gap remains regarding species‐specific characterization of whole plants, specifically with respect to roots, rhizomes, and belowground stems. Our objective was to quantify above‐ and belowground traits of four dominant dune grasses to document the potential for species‐specific effects on dune growth, maintenance, and erosion resistance. We examined above‐ and belowground traits among four prominent dune grasses of the Atlantic and Gulf Coasts of North America: Ammophila breviligulata, Panicum amarum, Spartina patens, and Uniola paniculata. Whole plant samples of each species were collected from the foredune at the US Army Engineer Research and Development Center's Field Research Facility in Duck, North Carolina, USA, and quantified for several above‐ and belowground traits (e.g., stem height, rhizome number and length, root surface area by diameter class, root tensile strength, and mycorrhizal percent infection). Belowground factors known to impact important dune processes, such as rhizome length, mycorrhizal percent infection, and root traits, differed substantially among species. When visualized in multivariate space, all species significantly differed in suites of above‐ and belowground traits. When considering belowground only, Ammophila and Spartina were similar, despite differences in biomass allocation. Species separated along axes related to mycorrhizal association, biomass allocation, and root construction. The four co‐occurring dune grass species were dissimilar in suites of plant traits. Belowground trait differences were driven by those describing root construction, biomass allocation, and mycorrhizal infection. Dissimilarity in above‐ and belowground suites of traits may demonstrate different approaches for surviving the dune environment. Incorporating belowground traits into modeling will enhance predictions of dune response to climate change through interactions between vegetation and dune dynamics that facilitate coastal resistance and resilience.
Seedlot Selection Tool and Climate‐Smart Restoration Tool: Web‐based tools for sourcing seed adapted to future climates
Authors: St.Clair John Bradley , Richardson Bryce A. , Stevenson‐Molnar Nikolas , Howe Glenn T. , Bower Andrew D. , Erickson Vicky J. , Ward Brendan , Bachelet Dominique , Kilkenny Francis F. , Wang Tongli
Published: May 2022

The Seedlot Selection Tool and Climate‐Smart Restoration Tool are web‐based tools designed to match seedlots with planting sites assuming that seedlots are adapted to the past climates in which they evolved, primarily with respect to temperature and aridity. The tools map the climatic match of seedlots with the past or projected climates of planting sites. The challenge is that future climates are a moving target, which means that seedlots must be adapted to the near‐term climates as well as the climates of the mid‐ to late‐21st century. Because climate projections are uncertain, the prudent approach is to aim for the warmest climate that may be expected while ensuring that seedlots moved from warmer to colder locales are not moved so far that they risk cold damage. Uncertainty in climate projections may be mitigated by ensuring genetic diversity through mixing seed sources and having collections from many parents per seed source. Three examples illustrate how to effectively use the web tools: (1) choosing seedlots targeting different future climates for a mid‐elevation Douglas‐fir site in the Washington Cascades, (2) finding current and future seed sources for restoration of big sagebrush after fires in the Great Basin and Snake River Plain, and (3) planning to ensure that a Douglas‐fir seed inventory includes seedlots suitable for future climates in western Oregon and Washington.
Inflammasome activation in end‐stage heart failure‐associated atrial fibrillation
Authors: Kugler Szilvia , Onódi Zsófia , Ruppert Mihály , Sayour Alex Ali , Oláh Attila , Benke Kálmán , Ferdinandy Péter , Merkely Béla , Radovits Tamás , Varga Zoltán V.
Published: May 2022

Aims

Inflammatory pathways are increasingly recognized as an important factor in the pathophysiology of both heart failure (HF) and atrial fibrillation (AF). However, there is no data about inflammation‐related histological and molecular alterations in HF‐associated AF. The objective of our study was to investigate inflammatory pathways and fibrosis in end‐stage HF‐associated AF.

Methods and results

Left atrial samples of 24 male patients with end stage ischemic HF undergoing heart transplantation were analysed. Twelve patients suffered from sustained AF while the others had no documented AF. The expression of inflammasome sensors and their downstream signalling were investigated by Western blot. No differences were observed in the expression of inflammasome sensors between the two groups, while cleaved caspase‐1 increased tendentiously in the AF group (P = 0.051). Cleaved caspase‐1 also showed significant correlation with the expression of interleukin‐1β and its cleaved form in the total population and in the AF group (P < 0.05). The presence of myocardial and epicardial macrophages were assessed by ionized calcium‐binding adaptor molecule 1 (Iba1) immunostaining. Number of macrophages showed a tendency towards elevation in the left atrial myocardium and epicardium of AF compared with SR group. The amount of total and interstitial fibrosis was determined on Masson's trichrome‐stained sections. Histological assessment revealed no difference between AF and SR groups in the amount of either total or interstitial fibrosis.

Conclusions

This is the first study on inflammation‐related differences between HF with SR or AF showing elevated inflammasome activity and enhanced macrophage infiltration in left atrial samples of patients with AF.
Multi‐variable biomarker approach in identifying incident heart failure in chronic kidney disease: results from the Chronic Renal Insufficiency Cohort study
Authors: Janus Scott E. , Hajjari Jamal , Chami Tarek , Mously Haytham , Badhwar Anshul K. , Karnib Mohamad , Carneiro Herman , Rahman Mahboob , Al‐Kindi Sadeer G.
Published: May 2022

Aims

Heart failure (HF) is one of the leading causes of cardiovascular morbidity and mortality in the ever‐growing population of patients with chronic kidney disease (CKD). There is a need to enhance early prediction to initiate treatment in CKD. We sought to study the feasibility of a multi‐variable biomarker approach to predict incident HF risk in CKD.

Methods and results

We examined 3182 adults enrolled in the Chronic Renal Insufficiency Cohort (CRIC) without prevalent HF who underwent serum/plasma assays for 11 blood biomarkers at baseline visit (B‐type natriuretic peptide [BNP], CXC motif chemokine ligand 12, fibrinogen, fractalkine, high‐sensitivity C‐reactive protein, myeloperoxidase, high‐sensitivity troponin T (hsTnT), fibroblast growth factor 23 [FGF23], neutrophil gelatinase‐associated lipocalin, fetuin A, aldosterone). The population was randomly divided into derivation (n = 1629) and validation (n = 1553) cohorts. Biomarkers that were associated with HF after adjustment for established HF risk factors were combined into an overall biomarker score (number of biomarkers above the Youden's index cut‐off value). Cox regression was used to explore the predictive role of a biomarker panel to predict incident HF. A total of 411 patients developed incident HF at a median follow‐up of 7 years. In the derivation cohort, four biomarkers were associated with HF (BNP, FGF23, fibrinogen, hsTnT). In a model combining all four biomarkers, BNP (hazard ratio [HR] 2.96 [95% confidence interval 2.14–4.09]), FGF23 (HR 1.74 [1.30–2.32]), fibrinogen (HR 2.40 [1.74–3.30]), and hsTnT (HR 2.89 [2.06–4.04]) were associated with incident HF. The incidence of HF increased with the biomarker score, to a similar degree in both derivation and validation cohorts: from 2.0% in score of 0% to 46.6% in score of 4 in the derivation cohort to 2.4% in score of 0% to 43.5% in score of 4 in the validation cohort. A model incorporating biomarkers in addition to clinical factors reclassified risk in 601 (19%) participants (352 [11%] participants to higher risk and 249 [8%] to lower risk) compared with clinical risk model alone (net reclassification improvement of 0.16).

Conclusion

A basic panel of four blood biomarkers (BNP, FGF23, fibrinogen, and hsTnT) can be used as a standalone score to predict incident HF in patients with CKD allowing early identification of patients at high‐risk for HF. Addition of biomarker score to clinical risk model modestly reclassifies HF risk and slightly improves discrimination.
Mixed‐Ligand Metal‐Organic Frameworks: Synthesis and Characterization of New MOFs Containing Pyridine‐2,6‐dimethanolate and Benzene‐1,4‐dicarboxylate Ligands
Authors: Mylonas‐Margaritis Ioannis , Mayans Júlia , Efthymiou Constantinos G. , McArdle Patrick , Papatriantafyllopoulou Constantina
Published: May 2022

The development of synthetic approaches towards new mixed‐ligand metal organic frameworks (MOFs) has been attracting considerable attention recently as they display fascinating properties due to the synergistic effect between the different ligands. Herein, the initial combination of pyridine‐2,6‐dimethanol (H2pdm) with benzene‐1,4‐dicarboxylic acid (H2bdc) has provided access to three new mixed‐ligand MOFs, [M3(bdc)2(Hpdm)2]n (MII=ZnII, 1; MnII, 2) and [Mn3(bdc)3(H2pdm)2]n (3). 1–3 are the first MOFs containing H2pdm in its neutral or anionic form. 1 and 2 are isostructural 2D MOFs with a square lattice (sql) framework topology, while 3 is a 3D MOF possessing a primitive cubic (pcu) topology. Dc magnetic susceptibility measurements for 3 demonstrate antiferromagnetic interactions between the MnII ions which is a combination of intra‐ and intertrimer exchange pathways.
1H‐Pyrazole‐Appended Pyridines and Their 1,2,4‐Triazine Precursors: A Rational Synthesis and in silico and in vitro Evaluation of Anti‐Cancer Activity
Authors: Krinochkin Alexey P. , Shtaitz Yaroslav K. , Rammohan Aluru , Butorin Ilya I. , Savchuk Maria I. , Khalymbadzha Igor A. , Kopchuk Dmitry S. , Slepukhin Pavel A. , Melekhin Vsevolod V. , Shcheglova Anna V. , Zyryanov Grigory V. , Chupakhin Oleg N.
Published: May 2022

An operationally facile and high yielding one‐pot protocol has been developed for the preparation of pyridines appended with pyrazole via NH linker. This protocol includes SNipso/aza‐Diels‐Alder reactions in up to 54 % yields starting from 1,2,4‐triazine precursors. All the synthesized compounds have been evaluated for their in silico activity against JAK1, SYK, and FAK1 kinases. The most promising compound was tested in vitro using A‐172, Hs578T, and HepG2 cancer cell lines and exhibited considerable cytotoxicity with IC50 values <50 μM in A‐172 and HepG2 cell lines. Anticancer in vitro activity correlates well with the predicted in silico data.
Cobalt‐Catalyzed C(sp2)−O Bond Formation by Directing Group Assisted C−H Activation
Authors: Park Jinhwan , Son Jongwoo
Published: May 2022

Metal‐catalyzed Csp2−H oxygenation is a synthetically invaluable transformation that enables the incorporation of synthetically useful functional groups, such as ethers and acetates, using a simple protocol. Compared to the well‐developed palladium catalysis, the catalysis of cobalt, a 3d‐transition metal, is recognized as a sustainable alternative for Csp2−H oxygenation because of the natural abundance of cobalt and cost‐effectiveness of the catalyst. In this Review, recent advances in cobalt‐catalyzed Csp2−H alkoxylation and acetoxylation are highlighted and several types of directing groups are discussed.