bluuebunny/crossref_metadata_2025 huggingface dataset:
Latent profile analyses of disordered eating behaviors and nonsuicidal self‐injury among Vietnamese adolescents
Authors: Zelkowitz Rachel L. , Cole David A. , Sterba Sonya K. , Liu Qimin , Lau Anna S. , Trung Lam T. , Weiss Bahr
Published: September 2022

Objective

Comorbidity of disordered eating (DE) behaviors and nonsuicidal self‐injury (NSSI) is linked to increased functional impairment. The present study identified subtypes of DE and NSSI comorbidity in a non‐Western, low‐ and middle‐income country where there has been particularly little research in this area.

Method

Latent profile analyses (LPA) were conducted to identify patterns of subgroup comorbidity in self‐reported DE behaviors and NSSI behaviors, in a sample of Vietnamese high‐school students (N = 1451, 51% female). Parallel‐process LPA was used to predict NSSI subgroup membership from DE subgroup membership.

Results

A seven‐class LPA model was identified for DE: (1) Low frequencies of all DE behaviors; (2) Frequent levels of all DE behaviors; (3) Frequent fasting and purging behaviors; (4) Frequent binge eating only; (5) Moderate binge eating; (6) Moderate fasting and purging behaviors; (7) Exercise and fasting. A two‐class (high versus low) model was identified for NSSI. Odds of membership in the high‐NSSI class were significantly increased for all DE classes except the class characterized by moderate binge eating. Odds of belonging to the high‐NSSI class were highest for those in DE classes involving purging behaviors. Males predominated in classes characterized by high behavior dysregulation.

Discussion

DE and NSSI represent important clinical concerns among Vietnamese youth in urban contexts, and males may show particular vulnerability for certain risk behaviors. The association of classes of DE behaviors to NSSI was particularly strong for classes that involved purging, highlighting the importance of this specific behavior for understanding comorbidity of DE and NSSI.

Public Significance

Disordered eating and nonsuicidal self‐injury (NSSI; hurting oneself without intending to die) commonly co‐occur. There has been less research on disordered eating and NSSI among individuals from non‐Western or low/middle‐income countries. We examined patterns of these behaviors in a school‐based sample of Vietnamese adolescents. We found that patterns of disordered eating distinguished by purging showed particular links to NSSI, which could have implications for screening and treatment.
Separate optogenetic manipulation of Nerve/glial antigen 2 (NG2) glia and mural cells using the NG2 promoter
Authors: Oishi Mitsuhiro , Passlick Stefan , Yamazaki Yoshihiko , Unekawa Miyuki , Adachi Ruka , Yamada Mayumi , Imayoshi Itaru , Abe Yoshifumi , Steinhäuser Christian , Tanaka Kenji F.
Published: September 2022

Nerve/glial antigen 2 (NG2) is a protein marker of NG2 glia and mural cells, and NG2 promoter activity is utilized to target these cells. However, the NG2 promoter cannot target NG2 glia and mural cells separately. This has been an obstacle for NG2 glia‐specific manipulation. Here, we developed transgenic mice in which either cell type can be targeted using the NG2 promoter. We selected a tetracycline‐controllable gene induction system for cell type‐specific transgene expression, and generated NG2‐tetracycline transactivator (tTA) transgenic lines. We crossed tTA lines with the tetO‐ChR2 (channelrhodopsin‐2)‐EYFP line to characterize tTA‐dependent transgene induction. We isolated two unique NG2‐tTA mouse lines: one that induced ChR2‐EYFP only in mural cells, likely due to the chromosomal position effect of NG2‐tTA insertion, and the other that induced it in both cell types. We then applied a Cre‐mediated set‐subtraction strategy to the latter case and eliminated ChR2‐EYFP from mural cells, resulting in NG2 glia‐specific transgene induction. We further demonstrated that tTA‐dependent ChR2 expression could manipulate cell function. Optogenetic mural cell activation decreased cerebral blood flow, as previously reported, indicating that tTA‐mediated ChR2 expression was sufficient to impact cellular function. ChR2‐mediated depolarization was observed in NG2 glia in acute hippocampal slices. In addition, ChR2‐mediated depolarization of NG2 glia inhibited their proliferation but promoted their differentiation in juvenile mice. Since the tTA–tetO combination is expandable, the mural cell–specific NG2‐tTA line and the NG2 glia‐specific NG2‐tTA line will permit us to conduct observational and manipulation studies to examine in vivo function of these cells separately.
The effect of adjuvant radiotherapy on clinical outcomes in early major salivary gland cancer
Authors: Hong Wei‐Ju , Chang Shih‐Lun , Tsai Chia‐Jen , Wu Hung‐Chang , Chen Yi‐Chen , Yang Ching‐Chieh , Ho Chung‐Han
Published: September 2022

Background

This study investigated the effects of adjuvant radiotherapy on outcomes in early‐stage major salivary gland cancers.

Methods

A total of 655 patients were identified, including 355 (54.2%) received adjuvant radiotherapy and 300 (45.8%) had surgery alone. The effect of adjuvant radiotherapy on 5‐year locoregional recurrence and disease‐specific survival (DSS) was calculated using the Kaplan–Meier method, Wilcoxon rank sum test, and Cox proportional hazards model.

Results

There were no significant differences in locoregional recurrence and DSS between patients receiving adjuvant radiotherapy and those not in both univariate and multivariable analysis. Although patients with positive margin status had a higher locoregional recurrence and those with moderate/poor differentiation had a worse DSS, stratified analysis still indicated there were no protective effects from the use of adjuvant radiotherapy.

Conclusions

The use of adjuvant radiation therapy was not associated with improved locoregional recurrence and DSS, even for those with high‐risk histopathological factors.
Simulating the distribution of rainfall interception ratio in a Masson's pine plot using terrestrial laser scanning data
Authors: Wu Bingxiao , Zheng Guang , Zhang Wuming , Chen Yang , Gu Zhujun , Zeng Maimai , Li Aiguang
Published: September 2022

The distribution and structure of leaves and branches influence the rainfall interception ratio (RIR) and water cycling processes in forests. However, measuring the three‐dimensional structure features of canopy organs to evaluate their effects on the RIR is labour‐intensive and time‐consuming. Modelling the spatial distribution of the RIR within a forest canopy after rainfall thus remains challenging. To address this difficulty, we used point clouds scanned by a terrestrial laser scanner (TLS) from Masson's Pines to extract fine‐scale canopy structure features. Next, we applied an exploratory factor analysis (EFA) to evaluate quantitatively how the various canopy structure features affect the RIR of canopy components. Finally, we simulated the RIR distribution by combining the interception coefficient of canopy organs estimated from the EFA results and throughfall volume measured by rain gauges set in the study site. The results show that the inclination angle of canopy organs and their upper gap fraction more strongly affect their RIR. The average absolute error of simulated rainfall interception volume (VIN) is less than 0.57 mm, and the related root mean squared error (RMSE) is less than 0.41 mm after rainfall. For measured rainfall events, the mean absolute error and RMSE of simulated VIN intercepted by nearby canopy organs above each rain gauge are less than 0.52 and 0.39 mm, respectively. The accuracy of the RIR simulation is degraded by the uneven distribution of canopy receivable rainfall volume, noise and missing point clouds in the TLS datasets. Modelling RIR distribution within the canopy based on TLS point clouds provides a chance for simulating water cycling processes in forests during rainfall.
Predicting earthquake preparedness intention among Croatian residents: Application of the theory of planned behaviour
Authors: Vrselja Ivana , Pandžić Mario , Glavaš Dragan
Published: September 2022

After several earthquakes occurred in Croatia in 2020, it became clear that the country's inhabitants were not prepared for seismic hazards. The aim of this study was to investigate what factors determine intention to prepare for earthquakes, based on the Theory of Planned Behaviour. A cross‐sectional study was conducted with 374 participants (70.1% women) aged 18–64 years. Participants self‐reported their attitudes toward earthquake preparedness, subjective norms, perceived behavioural control, and intention to prepare for an earthquake. Structural equation modelling showed that stronger intention to prepare for an earthquake was predicted by more positive attitudes toward earthquake preparedness and by more supportive subjective norms relating to earthquake preparedness. In contrast, perceived behavioural control was not associated with intention to prepare for an earthquake, nor did it moderate the association of attitudes or subjective norms with such intention. These results suggest that attitudes and subjective norms relating to earthquake preparedness are important factors that should be considered in future programmes to improve earthquake preparedness in the Croatian population.
Producing chemically accurate atomic Gaussian process regression models by active learning for molecular simulation
Authors: Burn Matthew J. , Popelier Paul L. A.
Published: September 2022

Machine learning is becoming increasingly more important in the field of force field development. Never has it been more vital to have chemically accurate machine learning potentials because force fields become more sophisticated and their applications expand. In this study a method for developing chemically accurate Gaussian process regression models is demonstrated for an increasingly complex set of molecules. This work is an extension to previous work showing the progression of the active learning technique in producing more accurate models in much less CPU time than ever before. The per‐atom active learning approach has unlocked the potential to generate chemically accurate models for molecules such as peptide‐capped glycine.
Screening for differentially expressed microRNAs in BALF and blood samples of infected COVID‐19 ARDS patients by small RNA deep sequencing
Authors: Najafipour Reza , Mohammadi Davood , Estaki Zohreh , Zarabadi Kiana , Jalilvand Manijeh , Moghbelinejad Sahar
Published: September 2022

Background

The pandemic COVID‐19 has caused a high mortality rate and poses a significant threat to the population of the entire world. Due to the novelty of this disease, the pathogenic mechanism of the disease and the host cell's response are not yet fully known, so lack of evidence prevents a definitive conclusion about treatment strategies. The current study employed a small RNA deep‐sequencing approach for screening differentially expressed microRNA (miRNA) in blood and bronchoalveolar fluid (BALF) samples of acute respiratory distress syndrome (ARDS) patients.

Methods

In this study, BALF and blood samples were taken from patients with ARDS (n = 5). Control samples were those with suspected lung cancer candidates for lung biopsy (n = 3). Illumina high‐throughput (HiSeq 2000) sequencing was performed to identify known and novel miRNAs differentially expressed in the blood and BALFs of ARDS patients compared with controls.

Results

Results showed 2234 and 8324 miRNAs were differentially expressed in blood and BALF samples, respectively. In BALF samples, miR‐282, miR‐15‐5p, miR‐4485‐3p, miR‐483‐3p, miR‐6891‐5p, miR‐200c, miR‐4463, miR‐483‐5p, and miR‐98‐5p were upregulated and miR‐15a‐5p, miR‐548c‐5p, miR‐548d‐3p, miR‐365a‐3p, miR‐3939, miR‐514‐b‐5p, miR‐513a‐3p, miR‐513a‐5p, miR‐664a‐3p, and miR‐766‐3p were downregulated. On the contrary, in blood samples miR‐15b‐5p, miR‐18a‐3p, miR‐486‐3p, miR‐486‐5p, miR‐146a‐5p, miR‐16‐2‐3p, miR‐6501‐5p, miR‐365‐3p, miR‐618, and miR‐623 were top upregulated miRNAs and miR‐21‐5p, miR‐142a‐3p, miR‐181‐a, miR‐31‐5p, miR‐99‐5p, miR‐342‐5p, miR‐183‐5p, miR‐627‐5p, and miR‐144‐3p were downregulated miRNAs. Network functional analysis for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), in ARDS patients' blood and BALF samples, showed that the target genes were more involved in activating inflammatory and apoptosis process.

Conclusion

Based on our results, the transcriptome profile of ARDS patients would be a valuable source for understanding molecular mechanisms of host response and developing clinical guidance on anti‐inflammatory medication.
Novel compound heterozygous synonymous and missense variants in the MYO7A gene identified by next‐generation sequencing in a Chinese family with nonsyndromic hearing loss
Authors: Xiang Yanbao , Xu Chenyang , Xu Yunzhi , Zhou Lili , Tang Shaohua , Xu Xueqin
Published: September 2022

Background

Variants in the MYO7A gene are increasingly identified among patients suffering from Usher syndrome type 1B (USH1B). However, such mutations are less commonly detected among patients suffering from nonsyndromic hearing loss (NSHL), including autosomal recessive deafness (DFNB2) and autosomal dominant deafness (DFNA11). This research attempts to clarify the genetic base of DFNB2 in a Chinese family and determine the pathogenicity of the identified mutations.

Method

Targeted next‐generation sequencing (TGS) of 127 known deafness genes was performed for the 14‐year‐old proband. Then, Sanger sequencing was performed on the available family members. A minigene splicing assay was performed to verify the impact of the novel MYO7A synonymous variant. After performing targeted next‐generation sequencing (TGS) of 127 existing hearing loss‐related genes in a 14‐year‐old proband, Sanger sequencing was carried out on the available family members. Then, to confirm the influence of the novel MYO7A synonymous variants, a minigene splicing assay was performed.

Results

Two heteroallelic mutants of MYO7A (NM_000260.3) were identified: a maternally inherited synonymous variant c.2904G > A (p.Glu968=) in exon 23 and a paternally inherited missense variant c.5994G > T (p.Trp1998Cys) in exon 44. The in vitro minigene expression indicated that c.2904G > A may result in skipping of exon 23 resulting in a truncated protein.

Conclusions

We reported a novel missense (c.5994G > T) and identified, for the first time, a novel pathogenic synonymous (c.2904G > A) variant within MYO7A in a patient with DFNB2. These findings enrich our understanding of the MYO7A variant spectrum of DFNB2 and can contribute to accurate genetic counseling and diagnosis of NSHL patients.
Brazilian green propolis improves gut microbiota dysbiosis and protects against sarcopenic obesity
Authors: Okamura Takuro , Hamaguchi Masahide , Bamba Ryo , Nakajima Hanako , Yoshimura Yuta , Kimura Tomonori , Hashimoto Yoshitaka , Majima Saori , Senmaru Takafumi , Ushigome Emi , Nakanishi Naoko , Asano Mai , Yamazaki Masahiro , Nishimoto Yuichiro , Yamada Takuji , Fujikura Chizuru , Asama Takashi , Okumura Nobuaki , Takakuwa Hiroshi , Sasano Ryoichi , Fukui Michiaki
Published: September 2022

Introduction

Brazilian green propolis is an important honeybee product that is considered beneficial for health. Here, we examined the therapeutic potential of dietary supplementation with propolis against sarcopenic obesity using Db/Db mice.

Methods

Db/m mice fed a normal diet alone and Db/Db mice fed normal diet alone, or supplemented with different amounts of propolis (0.08, 0.4 and 2%), were examined for effects on sarcopenic obesity.

Results

Propolis improved the glucose tolerance (P < 0.001), increased the grip strength (P < 0.001) and the weight of soleus (P = 0.006) and plantaris muscles (P = 0.008). Moreover, propolis improved the non‐alcoholic fatty liver disease activity score (P < 0.001) and decreased the expression of genes related to inflammation, liver fibrosis and fatty acid metabolism. Propolis decreased the accumulation of saturated fatty acids in the liver and increased their excretion in faeces. With regard to the innate immunity, propolis decreased the ratio of M1 macrophages (P = 0.008) and Type 1 and 3 innate lymphoid cells to CD45‐positive cells (P < 0.001) and increased the ratio of M2 macrophages (P = 0.002) and ILC2s (P = 0.007) in the liver. Additionally, propolis decreased the expression of genes related to muscle atrophy and inflammation and the concentration of saturated fatty acids in the soleus muscle. 16S rRNA phylogenetic sequencing revealed that propolis increased the Bacteroidetes/Firmicutes ratio, and the abundance of Butyricicoccus and Acetivibrio genera. Gut microbiota related to the pentose phosphatase pathway and glycerolipid metabolism was more prevalent after the administration of propolis.

Conclusions

This is the first study to demonstrate that propolis can improve sarcopenic obesity by improving dysbiosis due to overeating and provides new insights into diet–microbiota interactions during sarcopenic obesity.
Practice patterns of postgraduate trained dentists in the United States
Authors: Mertz Elizabeth A. , Bates Timothy , Kottek Aubri , Jura Matthew , Werts Miranda , Munson Bradley , Vujicic Marko
Published: September 2022

Objective

Postgraduate dental (PGD) primary care training has grown significantly. This study examines the individual, educational, community, and policy factors that predict practice patterns of PGD‐trained dentists.

Study design

Individual dentist records from the 2017 American Dental Association Masterfile, with indicators of Medicaid participation and practice in a Federally Qualified Health Center (FQHC), were linked to postdoctoral training, community/practice location, and state policy factors. Generalized logistic models, adjusted for these factors, were used to predict PGD‐trained dentists: (1a) serving Medicaid children, (1b) accepting new Medicaid patients, and (2) working in an FQHC.

Results

Individual attributes that predicted serving Medicaid children included all race/gender combinations (vs. White females), and foreign‐trained dentists and contractors/employees/associates (vs. practice owners). Black women are most likely to work in an FQHC. Residency attributes that predicted serving Medicaid children and working in an FQHC were Health Resources and Services Administration postdoctoral funding and being community based. Dentists practicing in rural or high‐poverty communities were more likely to serve Medicaid children and work at FQHCs. States with higher levels of graduate medical education investment, higher Medicaid rates, and more generous adult dental Medicaid benefits increased the likelihood of serving Medicaid children, while states with more expansive adult dental Medicaid benefits increased the likelihood of working in an FQHC.

Conclusion

Federal training investment in PGD education combined with Medicaid payment and coverage policies can strongly impact access to dental care for vulnerable populations. Yet, oral health equity cannot be achieved without increasing dentist workforce diversity.
An exploration of engineering instructors' pedagogical adaptations early in the COVID‐19 pandemic
Authors: Manierre Matthew J. , DeWaters Jan , Rivera Seema , Whalen Martha
Published: September 2022

Background

Many instructors made an emergency shift to online teaching during the Spring 2020 semester. There is reason to expect that instructors would have dramatically changed their pedagogy and teaching philosophies. At the same time, there are reasons that engineering instructors might be hesitant to introduce some changes to their courses.

Purpose/Hypothesis

This study explores pedagogical and philosophical adaptations using instructors' accounts of emergency remote teaching during the Spring 2020 semester.

Design/Method

In‐depth interviews with six engineering instructors were conducted to examine their teaching experiences and the way they responded to the online transition. Interview transcripts were analyzed for general themes and commonalities.

Results

Instructors made many changes during the transition, some of which were general and others individualized after a problem came to their attention. However, other changes were uncommon or even avoided, in particular, reducing content difficulty and shifting their teaching philosophies. Our interviews suggest several explanations for their choices, including the degree to which course design rendered change unnecessary, or the influence of the instructors' existing skillset, their desire to protect the validity of grades, and their sense of the scope of engineering pedagogy.

Conclusions

These interviews contribute to our understanding of how the emergency transition to online teaching impacted engineering instructors and how instructors might improve resilience during future crises. The conceptual tools and thought processes elucidated by this study can inform future analyses. Further research should pursue comparisons with other disciplines and consider the long‐term effects of pandemic teaching.
The identification of novel small extracellular vesicle (sEV) production modulators using luciferase‐based sEV quantification method
Authors: Yamamoto Aki , Takahashi Yuki , Inuki Shinsuke , Nakagawa Shumpei , Nakao Kodai , Ohno Hiroaki , Doi Masao , Takakura Yoshinobu
Published: September 2022

Small extracellular vesicles (sEVs) are nano‐sized vesicles secreted from various cells that contain bioactive metabolites and function as key regulators for intercellular communication. sEVs modulate diverse biological and pathological processes in the body, and the amount of circulating sEVs has been reported to correlate with certain disease progression. Therefore, the identification of small molecular compounds that can control sEV production may become a novel therapeutic strategy. In this study, a rapid, highly sensitive sEV quantification method utilizing fusion proteins consisting of Gaussia luciferase (gLuc) reporter protein and sEV markers (CD63 and CD82) was developed. A total of 480 compounds were screened to identify potent inducers and inhibitors of gLuc activity. Two novel compounds, KPYC08425 and KPYC12163, showed significant and dose‐dependent changes in gLuc activity with minimal cytotoxicity based on the LDH assay. The efficacy of these two compounds was further evaluated by protein quantification of the isolated sEVs. Further evaluation of KPYC12163 suggested that the autolysosomal pathway may be involved in its inhibitory effect on sEV production.
When cultural services and biodiversity matter most: Gaining a deeper insight into badlands ecosystem services preferences
Authors: Martínez‐Paz José M. , Albaladejo‐García José A. , Alcon Francisco
Published: September 2022

Most dryland ecosystems are characterised by a low ecosystem services (ES) provision, being socially perceived as lacking in cultural and regulating ES. This is the case of the badlands, highly eroded arid ecosystems without vegetation, which have been extensively analysed from a physical point of view, but hardly studied from the point of view of the benefits they provide to society. This paper aimed to determine the social preferences for and the relative importance of the ES provided by badlands. To achieve this objective, a representative sample of the population was taken from the Region of Murcia (Spain), a semiarid Mediterranean area with an abundant presence of these ecosystems. This study area is of additional interest for the provision of ES derived from agroecosystems. The contingent ranking method was used to identify aspects such as the utility provided by the different types of ES and the social well‐being derived from different management policies to be implemented. The results show a preference of the population for cultural ES and biodiversity in the badlands. Given that the implementation of badlands ES protection and a management policy based on the maintenance of agricultural ES are the two strategies that yield the highest social well‐being, the provisioning and regulating ES derived from agroecosystems in the area should be evaluated simultaneously, given the trade‐off that can occur between the two ecosystems. These results provide dryland ecosystem managers with a view of soil erosion management that is different from the traditional one, since it promotes not only its control, but also a greater presence of educational and recreational activities.
Demographic differences in the treatment of unilateral vocal fold paralysis
Authors: Patel Mit A. , Bock Jonathan M. , Blumin Joel H. , Friedland David R. , Adams Jazzmyne A. , Tong Ling , Osinski Kristen I. , Luo Jake
Published: September 2022

Objective

To determine the impact of patient demographics and social determinants of health on treatment pathways for unilateral vocal fold paralysis (UVFP) at a tertiary laryngology clinic.

Study design

Retrospective medical record review.

Methods

Patient demographics (age, gender, race, ethnicity, and insurance status) were extracted for adults diagnosed with UVFP between 2009 and 2019. Odds ratios for the associations between sociodemographic factors and UVFP treatment pathways were determined by chi‐square analyses.

Results

A total of 1490 UVFP diagnoses were identified during the study period with the majority being female (58%), White (85%), non‐Hispanic (97%), and publicly insured (54%). Five treatment pathways were identified: observation, injection laryngoplasty, voice therapy, laryngeal framework surgery/thyroplasty, and reinnervation surgery. There were 538 patients who underwent observation, 512 injection laryngoplasty, 366 voice therapy, 136 thyroplasty, and 26 laryngeal reinnervation surgery. Males were more likely to undergo injection laryngoplasty than females (OR 1.32; CI 1.08–1.61), whereas females were more likely to undergo voice therapy (OR 1.39; CI 1.09–1.76). Patients with public insurance (OR 1.48; CI 1.03–2.14) and Hispanics (OR 2.60; CI 1.18–5.72) were more likely to undergo thyroplasty. Patients who underwent reinnervation surgery were younger than those in other treatment pathways (median: 39.1 years vs. 50.7–56.1 years).

Conclusions

Gender, ethnicity, and insurance status were significantly associated with specific UVFP treatment pathways. Patients with public insurance were more likely to undergo surgical intervention than voice therapy. This data overall supports differences in care pathway utilization for UVFP based on social determinants of health.

Level of evidence

Level IV.
A Robust Strategy for Photoinitiated Macromolecular Thiol‐Ene Radical Coupling Reaction with High‐Efficiency Based on a RAFT‐Generated Thiol‐Terminated PDPA Reactant
Authors: Yan Lei , Liu Yuyang , Wang Zhiwen , Liu Huan
Published: September 2022

Thiol‐ene radical coupling reaction exhibits high chemical selectivity and rapid kinetics. In particular, the experiment of photoinitiated reaction has the advantages of facile operation and short reaction time. However, there are few reports on its application in macromolecular thiol‐ene coupling reaction in the presence of polymeric chains containing amine moieties. On the one hand, an amine agent itself may be involved in photoreaction; and on the other hand, amine moieties can create an alkaline environment, which may retard thiol‐ene radical reaction. In this paper, a well‐defined A(B‐L)2 type miktoarm star copolymer unit is investigated and synthesized, together with further A(B‐L)2C type one, by employing macromolecular thiol‐ene radical coupling reactions. In two copolymers, A, B, and C are poly(ε‐caprolactone) (PCL), poly(2‐(diisopropylamino) ethyl methacrylate) (PDPA), and poly(2‐methacryloyloxyethyl phosphorylcholine) (PMPC) arms, respectively, and L is terpyridine (tpy) ligand group and locates at the end of B arm. Especially, the synthesis of A(B‐L)2 type molecular architecture involved that a PDPA reactant (tpy‐PDPA‐SH) contains both a thiol end‐group and pendant tertiary amine moieties. Herein, such a macromolecular thiol‐ene radical coupling reaction is investigated and a robust synthesis strategy is reported.
An extension operator for Sobolev spaces with mixed weights
Authors: Hansen Markus , Schneider Cornelia , Szemenyei Flóra Orsolya
Published: September 2022

We provide an extension operator for weighted Sobolev spaces on polyhedral cones K involving a mixture of weights, which measure the distance to the vertex and the edges of the cone, respectively. Our results are based on Stein's extension operator for Sobolev spaces and generalize previous results of the first author.
Exploring dynamical complexity of a cannibalistic eco‐epidemiological model with multiple time delay
Authors: Biswas Santosh , Ahmad Bashir , Khajanchi Subhas
Published: September 2022

In this paper, we investigate a cannibalistic predator‐prey system with Beddington‐DeAngelis type response function when the infection only exists in the predator species. The predator species are subject to cannibalistic interaction and the infection spreads among the predators via cannibalism. The model is studied in presence of multiple delays for the maturation of prey and predator. Local stability analysis of the predator‐prey model around the biologically realistic two essential steady states is investigated. We also investigate the bifurcation analysis of the proposed model around the co‐existing steady states. Using the normal form method and center manifold theory, the direction of Hopf bifurcation and the Hopf bifurcating periodic solutions are explored. In presence of time delays, we derive the criteria for the permanence of the model. Our findings demonstrate that maturation delays destabilize the system and can produce high periodic oscillations. Cannibalism can act as a self‐regulatory scenario controlling the transmission of disease among the predator species and stabilizing the oscillations in the predator‐prey system. Our theoretical analysis is well supported with numerical simulation.
Spring‐infusors: How a simple and small solution can create king‐sized complexity
Authors: Laird Pamela , Burr Charlotte , Gill Fenella J. , Schultz André
Published: September 2022

Aim

The aims of the study were to investigate family and hospital staff views about the use of spring‐infusor devices for administration of intravenous antibiotic medications, to examine if the device is acceptable and feasible and to map a process for implementation.

Design

A qualitative study with a pragmatist approach, within a larger, mixed methods knowledge translation study.

Methods

Data were collected by semi‐structured interviews with patients who have cystic fibrosis and their parents and focus groups and interviews with hospital staff. Interviews were concluded when no new themes were identified. Thematic analysis and process mapping was undertaken.

Results

Six parents, nine children and 30 staff were interviewed. Families preferred spring‐infusors. Staff knowledge, experience and attitudes toward spring‐infusor use was varied. All staff acknowledged that their role is to support patient‐centred care. Spring‐infusors are preferred by families and clinicians above other IV administration devices but misconceptions about spring‐infusor use and numerous procedural challenges reduced their use.
Nucleation of electro‐active β and γ‐phases in P(VDF−HFP) for manufacturing energy harvesting device and self powered weight measuring device
Authors: Sk Asadullah , Adhikary Prakriti , Haldar Prabir Kr.
Published: September 2022

Highly electro‐active P(VDF−HFP)/Cu2+ films having more than 99% electro‐active phase was prepared by a simple solution casting method. We used this electro‐active polymer to make piezoelectric generators (PGs). These PGs can instantly light several LEDs just by repeated finger tapping. Using a bridge rectifier, by repeated finger tapping, capacitors were charged successfully by using these PGs. It is observed that when different people walk over these PGs they produce different voltage signals, indicating that these can be used as weight measuring device and in the field of intelligence. These indicate that there is potential for PGs to be used as self‐powered devices where mechanical vibrations can be utilized. Dielectric property of the polymer is also improved. This fabrication process of PGs is very easy and the cost of production is also very low. In our work, we have used very cheap salt as filler and got a very high amount (99%) of electro‐active phases. Also, we have got a very high piezoelectric output voltage (40 Volts) just by finger tapping on the simple device that we fabricated by using the polymer film.
Modeling psychological well‐being among abdominal and pelvic cancer patients: The roles of total pain, meaning in life, and coping
Authors: Krok Dariusz , Telka Ewa , Zarzycka Beata
Published: September 2022

Objective

Relationships between pain and well‐being are mediated by a variety of factors. This study examines a serial mediating role of meaning in life and coping in the relationship of total pain with psychological well‐being in abdominal and pelvic cancer (APC) patients. Total pain is understood in terms of physical, psychological, social, and spiritual components interacting upon one another.

Methods

Adult patients diagnosed with the APC (N = 333) who were undergoing radiotherapy/chemotherapy treatment in two inpatient units of university hospitals completed questionnaires measuring total pain, psychological well‐being, meaning in life, and coping. SEM analysis was used to examine serial mediation effects.

Results

All the dimensions of total pain were negatively associated with presence of meaning, coping strategies, and psychological well‐being. In contrast, the pain dimensions were positively associated with search for meaning. Presence of meaning, search for meaning, emotion‐ and meaning‐focused coping were serial mediators in the relationship between total pain and psychological well‐being.

Conclusions

Our results strongly suggests that a holistic examination of pain among patients with cancer is important for several reasons. They also indicate that psychological well‐being is significantly influenced by the serial interplay of personal meaning structures and coping abilities.
Type II congenital pulmonary airway malformation with primary ciliary dyskinesia in a 4‐year‐old child: A case report
Authors: Li Li , Liu Rou , Wang Yuanxiang , Wang Wenjian
Published: September 2022

A congenital pulmonary airway malformation (CPAM) combined with primary ciliary dyskinesia (PCD) has not been described in literature. Herein, we described the case of a 4‐year‐old boy who presented to us with recurrent productive cough and rhinorrhea for 2 years. High resolution computed tomography of the thorax revealed multiple, cystic, transparent shadows of different sizes near the posterior thoracic cavity in the lower lobe of the left lung. Thoracoscopic segmentectomy was carried out and histology confirmed a type II CPAM. Whole‐exome sequencing revealed a compound heterozygous mutation (c.10568+1G>A, c.9484delG) in the DNAH11 gene associated with PCD that originated from the boy's mother and father, respectively. This report showed that when a child with CPAM presents with a productive cough and recurrent sinusitis, irrespective of situs inversus, PCD should be suspected. Genetic testing can aid in diagnosis.
Thermodynamic coupling between neighboring binding sites in homo‐oligomeric ligand sensing proteins from mass resolved ligand‐dependent population distributions
Authors: Li Weicheng , Norris Andrew S. , Lichtenthal Katie , Kelly Skyler , Ihms Elihu C. , Gollnick Paul , Wysocki Vicki H. , Foster Mark P.
Published: September 2022

Homo‐oligomeric ligand‐activated proteins are ubiquitous in biology. The functions of such molecules are commonly regulated by allosteric coupling between ligand‐binding sites. Understanding the basis for this regulation requires both quantifying the free energy ΔG transduced between sites, and the structural basis by which it is transduced. We consider allostery in three variants of the model ring‐shaped homo‐oligomeric trp RNA‐binding attenuation protein (TRAP). First, we developed a nearest‐neighbor statistical thermodynamic binding model comprising microscopic free energies for ligand binding to isolated sites ΔG0, and for coupling between adjacent sites, ΔGα. Using the resulting partition function (PF) we explored the effects of these parameters on simulated population distributions for the 2N possible liganded states. We then experimentally monitored ligand‐dependent population shifts using conventional spectroscopic and calorimetric methods and using native mass spectrometry (MS). By resolving species with differing numbers of bound ligands by their mass, native MS revealed striking differences in their ligand‐dependent population shifts. Fitting the populations to a binding polynomial derived from the PF yielded coupling free energy terms corresponding to orders of magnitude differences in cooperativity. Uniquely, this approach predicts which of the possible 2N liganded states are populated at different ligand concentrations, providing necessary insights into regulation. The combination of statistical thermodynamic modeling with native MS may provide the thermodynamic foundation for a meaningful understanding of the structure–thermodynamic linkage that drives cooperativity.
Structure determination of an unstable macromolecular complex enabled by nanobody‐peptide bridging
Authors: Lorentzen Josefine , Pedersen Dennis Vestergaard , Gadeberg Trine Amalie Fogh , Andersen Gregers Rom
Published: September 2022

Structure determination of macromolecular complexes is challenging if subunits can dissociate during crystallization or preparation of electron microscopy grids. We present an approach where a labile complex is stabilized by linking subunits though introduction of a peptide tag in one subunit that is recognized by a nanobody tethered to a second subunit. This allowed crystal structure determination at 3.9 Å resolution of the highly non‐globular 320 kDa proconvertase formed by complement components C3b, factor B, and properdin. Whereas the binding mode of properdin to C3b is preserved, an internal rearrangement occurs in the zymogen factor B von Willebrand domain type A domain compared to the proconvertase not bound to properdin. The structure emphasizes the role of two noncanonical loops in thrombospondin repeats 5 and 6 of properdin in augmenting the activity of the C3 convertase. We suggest that linking of subunits through peptide specific tethered nanobodies represents a simple alternative to approaches like affinity maturation and chemical cross‐linking for the stabilization of large macromolecular complexes. Besides applications for structural biology, nanobody bridging may become a new tool for biochemical analysis of unstable macromolecular complexes and in vitro selection of highly specific binders for such complexes.
Differential impact of PI3K/AKT/mTOR signaling on tumor initiation and progression in animal models of prostate cancer
Authors: Wang Shuaibin , Zhang Chao , Xu Zhifang , Chen Michael H. , Yu Haiyan , Wang Lizhong , Liu Runhua
Published: September 2022

Background

The PI3K/AKT/mTOR signaling pathway is essential for initiation and progression of prostate cancer. However, there has been no a comprehensive comparison for the role of these signaling nodes in prostate tumor initiation and progression.

Methods

With genetically engineered animal models, we compared the impact of prostate‐specific deletions of Pten, Tsc1, and Tsc2 and activation of Akt1 on tumor initiation and progression. Also, we assessed the expression and genetic alterations of PTEN, AKT1, TSC1, and TSC2 in human primary prostate cancers.

Results

For the genetically engineered mice, prostate conditional knockout (cKO) of Pten, Tsc1, and Tsc2 led to initiation and progression of mouse prostatic neoplasia hyperplasia (mPIN). Akt1 transgenic mice developed more aggressive mPINs than mice with Tsc1 or Tsc2 single‐cKO, but the effect was more moderate than that for Pten single‐cKO or Tsc1/Tsc2 double‐cKO mice. Functional analyses showed that Pten single‐cKO, AKT1 activation, and Tsc1/Tsc2 double‐cKO induced cell proliferation more than Tsc1 or Tsc2 single‐cKO, but only Pten single‐cKO and AKT1 activation reduced epithelial adhesion. All cKO or AKT1 activation enhanced the phosphorylation of p‐S6 (S235/236) but only Pten single‐cKO and Tsc1/Tsc2 double‐cKO enhanced the phosphorylation of p‐AKT (S473) and p‐4EBP1 (T37/46/70). In human prostate cancers, PTEN, but not AKT1, TSC1, or TSC2 had frequent genetic alterations. However, as key signaling nodes, AKT1, TSC1, and TSC2 may be responsible for PTEN loss‐mediated tumor initiation and progression.

Conclusion

Our results for genetically engineered mouse models suggest a differential role of the PI3K/AKT/mTOR signaling nodes in prostate cancer initiation and progression, but the underlying molecular mechanisms remain unaddressed.
An adaptive biomarker basket design in phase II oncology trials
Authors: Liu Shufang , Takeda Kentaro , Rong Alan
Published: September 2022

The phase II basket trial in oncology is a novel design that enables the simultaneous assessment of treatment effects of one anti‐cancer targeted agent in multiple cancer types. Biomarkers could potentially associate with the clinical outcomes and re‐define clinically meaningful treatment effects. It is therefore natural to develop a biomarker‐based basket design to allow the prospective enrichment of the trials with the adaptive selection of the biomarker‐positive (BM+) subjects who are most sensitive to the experimental treatment. We propose a two‐stage phase II adaptive biomarker basket (ABB) design based on a potential predictive biomarker measured on a continuous scale. At Stage 1, the design incorporates a biomarker cutoff estimation procedure via a hierarchical Bayesian model with biomarker as a covariate (HBMbc). At Stage 2, the design enrolls only BM+ subjects, defined as those with the biomarker values exceeding the biomarker cutoff within each cancer type, and subsequently assesses the early efficacy and/or futility stopping through the pre‐defined interim analyses. At the end of the trial, the response rate of all BM+ subjects for each cancer type can guide drug development, while the data from all subjects can be used to further model the relationship between the biomarker value and the clinical outcome for potential future research. The extensive simulation studies show that the ABB design could produce a good estimate of the biomarker cutoff to select BM+ subjects with high accuracy and could outperform the existing phase II basket biomarker cutoff design under various scenarios.
Adaptive robust asymptotic tracking control of nonaffine nonlinear systems
Authors: Wang Shubo
Published: September 2022

This article investigates the barrier lyapunov function‐based adaptive robust control scheme for nonaffine nonlinear systems with unknown system dynamics. First, the nonaffine system is converted into affine system via a combination of first‐order filter and coordinate transformation, then a high‐gain observer is utilized to reconstruct the immeasurable states of the derived affine system. Second, a robust integral of the sign of the error (RISE) is incorporated into the control design to reject the unknown dynamics. Third, a barrier lyapunov function based design method is used to ensure that the input vector to the parameter estimation remain within a predefined region. Then, an adaptive robust control scheme with only one adaptive parameter by using the upper bound estimation is developed. Finally, numerical simulations validate the efficacy of the developed control scheme.
Integrated river water quality and quantity management based on undesirability and cost‐effectiveness
Authors: Pashmchi Parastoo , Taheriyoun Masoud , Asghari Keyvan
Published: September 2022

Integrated water resources management aims to simultaneously solve water shortage and contamination problems by considering economic, social, and environmental criteria. To that view, this study has developed a two‐objective optimization model regarding water allocation (WA) and wasteload allocation (WLA) in the Zayandehrood river basin, the central part of Iran. The model aimed to supply the users' water demand considering the downstream environmental flow to fulfill the social‐environmental requirements. Besides, satisfying the river water quality standards was regarded as the environmental‐economic criteria. The WA objective function minimizes the undesirability caused by reduced allocated water and downstream environmental flow. The QUAL2K model was used to simulate the wasteload discharge impacts on the river water quality. The water quality parameters included biochemical oxygen demand (BOD), TP, and TN for the urban and industrial wasteload and nitrate for the agricultural drainage. The results showed that a joint WA ‐ WLA optimization reduced the total average WA by 15% and increased the downstream flow by three times the base level. Also, the water quality violations of the standard limits were reduced by 18, 4, and 15 times for BOD, NO3, and TP, respectively.
Base Modifications of Nucleosides via the Use of Peptide‐Coupling Agents, and Beyond
Authors: Lakshman Mahesh K.
Published: September 2022

Several naturally occurring purine and pyrimidine nucleosides contain an amide linkage as part of the heterocyclic aglycone. Enolization of the amide and conversion to leaving groups at the amide carbon atom permits base modification by addition‐elimination types of processes. Although a number of methods have been developed over the years for accomplishing such conversions, the present Personal Account describes efforts from the Lakshman laboratories. Facile activation of the amido groups in nucleobases can be achieved with peptide‐coupling agents. Subsequent reaction with nucleophiles then accomplishes the base modifications. In many cases, the activation and displacement steps can be done as two‐step, one‐pot processes, whereas in other cases, discrete storable activated nucleosides can be isolated for subsequent displacement reactions. Using such an approach a wide range of nucleoside base modifications is readily achievable. In many instances, mechanistic investigations have been conducted so as to understand the activation process.
Anaesthetic management of a dog with a bidirectionally shunting patent ductus arteriosus and concurrent pulmonary hypertension
Authors: Ban Kaitlynn , Bini Gianluca , Herrold Emily , Stavri Alba , Winter Randolph
Published: September 2022

A 1‐year‐old, 9.8‐kg (21.6‐lb), female, spayed Pembroke Welsh corgi dog was presented for evaluation of previously diagnosed patent ductus arteriosus and severe pulmonary hypertension. In the veterinary literature, there is relatively little information related to the anaesthetic management of patients with patent ductus arteriosus and severe pulmonary hypertension (or in those with Eisenmenger pathophysiology). In this case report, we consider haemodynamic concerns related to anaesthesia in this clinical setting, while describing the successful management of this case and related complications.