bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying canonical and replicable multi‐scale intrinsic connectivity networks in 100k+ resting‐state fMRI datasets
Authors: Iraji A. , Fu Z. , Faghiri A. , Duda M. , Chen J. , Rachakonda S. , DeRamus T. , Kochunov P. , Adhikari B. M. , Belger A. , Ford J. M. , Mathalon D. H. , Pearlson G. D. , Potkin S. G. , Preda A. , Turner J. A. , van Erp T. G. M. , Bustillo J. R. , Yang K. , Ishizuka K. , Faria A. , Sawa A. , Hutchison K. , Osuch E. A. , Theberge J. , Abbott C. , Mueller B. A. , Zhi D. , Zhuo C. , Liu S. , Xu Y. , Salman M. , Liu J. , Du Y. , Sui J. , Adali T. , Calhoun V. D.
Published: October 2023

Despite the known benefits of data‐driven approaches, the lack of approaches for identifying functional neuroimaging patterns that capture both individual variations and inter‐subject correspondence limits the clinical utility of rsfMRI and its application to single‐subject analyses. Here, using rsfMRI data from over 100k individuals across private and public datasets, we identify replicable multi‐spatial‐scale canonical intrinsic connectivity network (ICN) templates via the use of multi‐model‐order independent component analysis (ICA). We also study the feasibility of estimating subject‐specific ICNs via spatially constrained ICA. The results show that the subject‐level ICN estimations vary as a function of the ICN itself, the data length, and the spatial resolution. In general, large‐scale ICNs require less data to achieve specific levels of (within‐ and between‐subject) spatial similarity with their templates. Importantly, increasing data length can reduce an ICN's subject‐level specificity, suggesting longer scans may not always be desirable. We also find a positive linear relationship between data length and spatial smoothness (possibly due to averaging over intrinsic dynamics), suggesting studies examining optimized data length should consider spatial smoothness. Finally, consistency in spatial similarity between ICNs estimated using the full data and subsets across different data lengths suggests lower within‐subject spatial similarity in shorter data is not wholly defined by lower reliability in ICN estimates, but may be an indication of meaningful brain dynamics which average out as data length increases.
Pre‐movement event‐related potentials and multivariate pattern of EEG encode action outcome prediction
Authors: Ody Edward , Kircher Tilo , Straube Benjamin , He Yifei
Published: October 2023

Self‐initiated movements are accompanied by an efference copy, a motor command sent from motor regions to the sensory cortices, containing a prediction of the movement's sensory outcome. Previous studies have proposed pre‐motor event‐related potentials (ERPs), including the readiness potential (RP) and its lateralized sub‐component (LRP), as potential neural markers of action feedback prediction. However, it is not known how specific these neural markers are for voluntary (active) movements as compared to involuntary (passive) movements, which produce much of the same sensory feedback (tactile, proprioceptive) but are not accompanied by an efference copy. The goal of the current study was to investigate how active and passive movements are distinguishable from premotor electroencephalography (EEG), and to examine if this change of neural activity differs when participants engage in tasks that differ in their expectation of sensory outcomes. Participants made active (self‐initiated) or passive (finger moved by device) finger movements that led to either visual or auditory stimuli (100 ms delay), or to no immediate contingency effects (control). We investigated the time window before the movement onset by measuring pre‐movement ERPs time‐locked to the button press. For RP, we observed an interaction between task and movement. This was driven by movement differences in the visual and auditory but not the control conditions. LRP conversely only showed a main effect of movement. We then used multivariate pattern analysis to decode movements (active vs. passive). The results revealed ramping decoding for all tasks from around −800 ms onwards up to an accuracy of approximately 85% at the movement. Importantly, similar to RP, we observed lower decoding accuracies for the control condition than the visual and auditory conditions, but only shortly (from −200 ms) before the button press. We also decoded visual vs. auditory conditions. Here, task is decodable for both active and passive conditions, but the active condition showed increased decoding shortly before the button press. Taken together, our results provide robust evidence that pre‐movement EEG activity may represent action‐feedback prediction in which information about the subsequent sensory outcome is encoded.
Blood pressure‐cerebral oxygen coupling model: A new approach for stroke risk prediction
Authors: Zhang Jingsha , Li Wenhao , Zhang Ke , Huo Congcong , Xu Gongcheng , Li Zengyong
Published: October 2023

Stroke is a major cause of death and disability worldwide, but predicting its risk remains challenging. This study aimed to evaluate the cerebral blood flow autoregulation function of subjects with different stroke risk levels and predict their stroke risk. The coupling strength between cerebral oxygen and blood pressure signals was calculated by wavelet analysis and dynamic Bayesian inference and used as a quantitative index of cerebral blood flow autoregulation. A stroke prediction model based on the extreme random tree was constructed using the coupling strength and other data as input features. The results showed that the coupling strength was significantly higher in the high‐risk group than the other groups. Moreover, the prediction model achieved an average accuracy of 0.80 across the three groups. The coupling strength of cerebral oxygen and blood pressure can be used as an objective index to predict stroke risk, which has implications for stroke prevention and intervention.
Motivation and accessing care among drug treatment court involved women: A sequential, mixed‐methods approach
Authors: Blank Lilo , Bandyopadhyay Sanjukta , Yang Hongmei , Williams Geoffrey , Cerulli Catherine , Verma Shelley , Anson Jacqueline , Connor Meghan , Morse Diane S.
Published: October 2023

Drug treatment courts (DTC) address substance use disorders (SUD) but not cooccurrencing HIV or hepatitis C virus (HCV). This pilot explored feasibility and preliminary outcomes of the Women's Initiative Supporting Health (WISH) intervention and health‐related motivation, both based in self‐determination theory (SDT) regarding HIV/HCV and SUD treatment. WISH feasibility study: 79 DTC women completed a one‐time survey regarding motivation and willingness to engage in future interventions. WISH intervention: 22 women from DTC with SUD and HIV or HCV received a 6‐session, peer motivational enhancement health behavior‐oriented interventions. Recruitment strategies were feasible. SDT‐based measures demonstrated internal consistency in this under‐studied population, with perceived competence/autonomy associationed with motivation to reduce HIV/HCV/SUD risk. Women DTC participants indicated acceptance and showed internally consistent results in SDT‐based motivation measures These WISH feasibility and intervention pilot studies lay a foundation for future studies addressing motivation to access healthcare among women DTC participants.
A scoping review of existing research between 1990 and 2023: Measuring virtual communities of practice across disciplines
Authors: Lardier David T. , Dickson Elizabeth L. , Hackett Janna M. , Verdezoto Carolina S.
Published: October 2023

Virtual communities of practice (VCoPs) can decrease social, structural, and professional isolation, provide opportunities for knowledge‐sharing abilities, and may improve participants' self‐reported sense of connectedness to one another and their profession. However, more research is needed to examine measurement of VCoPs effectiveness on participants. In this scoping review our research question was: What is the state of the science for VCoPs and how are these communities measured in current research specific to education and health/health education? Guided by Arksey and O'Malley's five stages for conducting a rigorous scoping review, we identified gaps in the evidence regarding the overall state of the science on measurement of VCoPs inclusive of quantitative and mixed‐methods literature describing validated VCoP measurement in both English or Spanish from January 1990 to July 2023, and within the health, education, or health education disciplines. Initial searches yielded 2350 articles. Authors independently screened papers and extracted data. The results of this scoping review (N = 13 articles) highlight the measurement of VCoPs specific to education, healthcare, health education research. We found that measures had been tested in VCoPs within health, education, health education, and professional education information technologies disciplines, with the Community of Inquiry framework being the most common theoretical foundation. The findings provide an understanding of measurement tools and impacts and outcomes of VCoP participation and we make recommendations for future VCoP measurement tool development.
Revolutionizing Human papillomavirus (HPV)‐related cancer therapies: Unveiling the promise of Proteolysis Targeting Chimeras (PROTACs) and Proteolysis Targeting Antibodies (PROTABs) in cancer nano‐vaccines
Authors: Mukerjee Nobendu , Maitra Swastika , Gorai Sukhamoy , Ghosh Arabinda , Alexiou Athanasiosis , Thorat Nanasaheb D.
Published: October 2023

Personalized cancer immunotherapies, combined with nanotechnology (nano‐vaccines), are revolutionizing cancer treatment strategies, explicitly targeting Human papilloma virus (HPV)‐related cancers. Despite the availability of preventive vaccines, HPV‐related cancers remain a global concern. Personalized cancer nano‐vaccines, tailored to an individual's tumor genetic mutations, offer a unique and promising solution. Nanotechnology plays a critical role in these vaccines by efficiently delivering tumor‐specific antigens, enhancing immune responses, and paving the way for precise and targeted therapies. Recent advancements in preclinical models have demonstrated the potential of polymeric nanoparticles and high‐density lipoprotein‐mimicking nano‐discs in augmenting the efficacy of personalized cancer vaccines. However, challenges related to optimizing the nano‐carrier system and ensuring safety in human trials persist. Excitingly, the integration of nanotechnology with Proteolysis‐Targeting Chimeras (PROTACs) provides an additional avenue to enhance the effectiveness of personalized cancer treatment. PROTACs selectively degrade disease‐causing proteins, amplifying the impact of nanotechnology‐based therapies. Overcoming these challenges and leveraging the synergistic potential of nanotechnology, PROTACs, and Proteolysis‐Targeting Antibodies hold great promise in pursuing novel and effective therapeutic solutions for individuals affected by HPV‐related cancers.
The effect of a multicomponent oral care regimen on gingival inflammation: A randomized controlled clinical trial
Authors: do Amaral Guilherme C. L. S. , Hassan Mohamed A. , Saraiva Luciana , Nakao Laís Y. S. , Holzhausen Marinella , Malheiros Zilson M. , Stewart Bernal , Romito Giuseppe A. , Villar Cristina C.
Published: October 2023

Background

Oral care regimens can be explored to improve oral health in patients with gingivitis. This study aimed to evaluate the efficacy of a multicomponent oral care regimen with a dual zinc plus arginine (DZA) toothpaste and cetylpyridinium chloride with zinc lactate (CPC + Zn) mouthwash in reducing gingival bleeding in patients with gingivitis.

Methods

This randomized clinical trial included 94 participants with gingivitis who were randomized into two groups: the DZA/CPC + Zn group, which used a 1450‐ppm fluoride toothpaste containing 0.96% zinc plus 1.5% arginine and a fluoride‐containing mouthwash with 0.075% CPC and 0.28% zinc lactate, and the control group, which used a 1450‐ppm fluoride toothpaste and a placebo mouthwash for 6 months. All participants were examined by a blinded examiner who measured the gingival index, plaque index, and gingival severity index. Data were analyzed using paired t test, independent t test, and analysis of covariance (ANCOVA).

Results

Both groups presented statistically significant reductions in all clinical parameters compared to baseline. The DZA/CPC + Zn group exhibited significantly greater reductions in gingival index, gingival severity index, proximal gingival index, plaque index and proximal plaque index compared to the control group at 1, 3, and 6 months. Furthermore, DZA/CPC + Zn significantly decreased the percentage of patients with generalized gingivitis over a 6‐month follow‐up period. However, differences between the DZA/CPC + Zn and the control groups were not maintained after both groups established similar regimens with fluoride toothpaste.

Conclusion

The multicomponent oral care regimen consisting of DZA toothpaste and CPC + Zn mouthwash is effective in reducing gingival inflammation and supragingival biofilm in patients with gingivitis.
Focal surface projection: Extending projector depth of field using a phase‐only spatial light modulator
Authors: Ueda Fumitaka , Kageyama Yuta , Iwai Daisuke , Sato Kosuke
Published: October 2023

We present a focal surface projection to solve the narrow depth‐of‐field problem in projection mapping applications. We apply a phase‐only spatial light modulator to realize nonuniform focusing distances, whereby the projected contents appear focused on a surface with considerable depth variations. The feasibility of the proposed technique was validated through a physical experiment.
Head–neck melanoma: Clinical, histopathological and prognostic features of an Italian multicentric study
Authors: Schipani Giusy , Nisticò Steven P. , Quaglino Pietro , Ribero Simone , Gallo Giuseppe , Maione Vincenzo , Girolomoni Giampiero , Rosina Paolo , Alaibac Mauro , Messina Francesco , Gatti Alessandro , Stinco Giuseppe , Buligan Cinzia , Bassoli Sara , Farnetani Francesca , Borghi Alessandro , Melandri Davide , Sirna Riccardo , Feci Luca , Simonetti Stefano , Stingeni Luca , Offidani Annamaria , Brisigotti Valerio , Campanati Anna , Calvieri Stefano , Spallone Giulia , Botti Elisabetta , Panasiti Vincenzo , Pagnanelli Gianluca , Scalvenzi Massimiliano , Fabbrocini Gabriella , Costa Claudia , Schirripa Vincenzo , Borgia Francesco , Atzori Laura , Scali Elisabetta , Passante Maria , Guarneri Fabrizio , Patruno Cataldo
Published: October 2023

Background

Primitive location of melanoma could be a relevant prognostic factor. As regards the scalp, some studies indicate a particularly aggressive biological behaviour for this anatomical localisation.

Objectives

In this multicentric study, data regarding head–neck melanoma (HNM) have been revised.

Methods

The design of the study included two main phases. In this retrospective study, data regarding HNM have been collected and analysed.

Results

In summary, our data suggest that the posterior neck is the area most affected by thicker melanomas. Cheeks and neck melanoma are associated with reduced disease‐free years of life and overall survival compared with all other sites of HNM.

Conclusions

This study provides useful information in defining the clinical features of HNM, thus improving diagnosis and treatment strategies.
Prevalence of multiple long‐term conditions with psoriasis in England: A cohort study using the Clinical Practice Research Datalink
Authors: Payne Katherine , Ciamponi Federica , Allen Thomas , Thompson Alex J. , Gkountouras Georgios , Gavan Sean P. , Reid Claire T. , Griffiths Christopher E. M. , Ashcroft Darren M.
Published: October 2023

Background

People with psoriasis live with other long‐term conditions (co‐morbidities) that affect their use of healthcare, but the scale of this is not well characterised.

Objectives

Estimate the concurrent prevalence of co‐morbidities known to affect the use of healthcare in people living with psoriasis in England.

Methods

A retrospective cohort study using linked data from the UK's Clinical Practice Research Datalink with Hospital Episode Statistics, Office for National Statistics mortality records, and Index of Multiple Deprivation 2010. A cohort of adults (≥18 years) with psoriasis was matched with a comparator cohort of individuals based on age, sex and registered general practice between April 2007 and December 2017. A predefined list of 21 co‐morbidities was selected from a published measure: the Cambridge Multimorbidity Index (CMI). Descriptive analysis describes prevalence with statistical tests (t tests; two‐sample proportions test) of difference for selected variables.

Results

The study cohort comprised 372,949 individuals (54,817 psoriasis; and 318,132 matched‐comparator). The calculated CMI general score was statistically higher at 0.54 (standard deviation: 0.9) for psoriasis compared with 0.39 (standard deviation: 0.75) for the matched comparator (t test; p < 0.001). A higher percentage (53.2%) of individuals within the psoriasis cohort had at least one co‐morbidity compared with 45.4% of individuals in the matched‐comparator cohort. The prevalence of 20 individual co‐morbidities was statistically significantly (two‐sample proportions test; p < 0.001) higher than in the matched‐comparator cohort.

Conclusions

Individuals living with psoriasis are more likely to live with multiple long‐term conditions that have developed at an earlier age compared with those without psoriasis. Knowing the characteristics for a higher prevalence of co‐morbidities in people living with psoriasis provides clinicians with the motivation to consider more holistic approaches to improve management and treatment, noting the importance of mental health alongside physical health, and enabling a conversation about the importance of making lifestyle changes.
Quantifying Localized Stresses in the Matrix of a Fiber‐Reinforced Composite via Mechanophores
Authors: Haque Nazmul , Gohl Jared , Chang Chia‐Chih , Chang Hao Chun , Davis Chelsea S.
Published: October 2023

Understanding the stress distribution within fiber‐reinforced polymers (FRPs) is critical to extending their operational lifespan. The integration of mechanoresponsive molecular force probes, referred to as mechanophores, presents a potential solution by enabling direct monitoring of stress concentrations. In this study, spiropyran (SP) mechanophores (MPs) are embedded within a polydimethylsiloxane (PDMS) matrix to visualize stress localization during loading within a single fiber‐reinforced framework. The SP mechanophore undergoes a transition from a non‐fluorescent state to an active state (merocyanine) through isomerization in response to mechanical forces. Using a single fiber mounted axially within the matrix, the fundamental failure modes observed in conventional fiber‐reinforced composites are replicated. Samples are strained under uniaxial tensile loading along the fiber direction and the localization of stresses is observed via MP activation. Stresses are concentrated in the matrix near the fiber region that gradually decreases away from the fiber surface. Confocal microscopy is used to visualize mechanophore activation and quantitatively assess fluorescence intensity. Finite element modeling is used to develop a calibration to quantify the stresses based on the observed fluorescence intensity. These outcomes underscore the viability of employing these mechanoresponsive molecules as a potential means to visualize real‐time stress distribution, thereby facilitating the design of high‐performance composites.
Improving the effectiveness of personalized recommendations through attributional cues
Authors: Weidig Jakob , Kuehnl Christina
Published: October 2023

Firms often employ personalized recommendations to help customers make purchase decisions. To improve the effectiveness of their personalized recommendations, some firms use cues to offer transparency on how they collect and use data to derive recommendations. We draw on attribution theory to propose an additional mechanism to improve the effectiveness of personalized recommendations with cues. Attributional cues, which refer to the underlying data (i.e., customers' own data vs. similar customers' data) used for personalized recommendations, aim to increase customers' self‐attribution of personalized recommendations. Specifically, in three experimental studies, we show that attributional cues increase customers' self‐attribution of personalized recommendations, leading to higher trust in and lower reactance to personalized recommendations. The accuracy and valence of the personalized recommendations moderate this attributional effect. As a result, employing attributional cues can be an essential and affordable tool for firms to increase the effectiveness of their personalized recommendations.
A systems biology approach and in vitro experiment indicated Rapamycin targets key cancer and cell cycle‐related genes and miRNAs in triple‐negative breast cancer cells
Authors: Tafti Ali , Shojaei Samaneh , Zali Hakimeh , Karima Saeed , Mohammadi‐Yeganeh Samira , Mondanizadeh Mahdieh
Published: October 2023

An anticancer drug known as Rapamycin acts by inhibiting the mammalian target of the Rapamycin pathway. This agent has recently been investigated for its potential therapeutic benefits in sensitizing drug‐resistant breast cancer (BC) treatment. The molecular mechanism underlying these effects, however, is still a mystery. Using a systems biology method and in vitro experiment, this study sought to discover essential genes and microRNAs (miRNAs) targeted by Rapamycin in triple‐negative BC (TNBC) cells to aid prospective new medications with less adverse effects in BC treatment. We developed the transcription factor‐miRNA‐gene and protein−protein interaction networks using the freely accessible microarray data sets. FANMOD and MCODE were utilized to identify critical regulatory motifs, clusters, and seeds. Then, functional enrichment analyses were conducted. Using topological analysis and motif detection, the most important genes and miRNAs were discovered. We used quantitative real‐time polymerase chain reaction (qRT‐PCR) to examine the effect of Rapamycin on the expression of the selected genes and miRNAs to verify our findings. We performed flow cytometry to investigate Rapamycin's impact on cell cycle and apoptosis. Furthermore, wound healing and migration assays were done. Three downregulated (PTGS2, EGFR, VEGFA) and three upregulated (c‐MYC, MAPK1, PIK3R1) genes were chosen as candidates for additional experimental verification. There were also three upregulated miRNAs (miR‐92a, miR‐16, miR‐20a) and three downregulated miRNAs (miR‐146a, miR‐145, miR‐27a) among the six selected miRNAs. The qRT‐PCR findings in MDA‐MB‐231 cells indicated that c‐MYC, MAPK1, PIK3R1, miR‐92a, miR‐16, and miR‐20a expression levels were considerably elevated following Rapamycin treatment, whereas PTGS2, EGFR, VEGFA, miR‐146a, and miR‐145 expression levels were dramatically lowered (p < 0.05). These genes are engaged in cancer pathways, transcriptional dysregulation in cancer, and cell cycle, according to the top pathway enrichment findings. Migration and wound healing abilities of the cells declined after Rapamycin treatment, and the number of apoptotic cells increased. We demonstrated that Rapamycin suppresses cell migration and metastasis in the TNBC cell line. In addition, our data indicated that Rapamycin induces apoptosis in this cell line. The discovered vital genes and miRNAs affected by Rapamycin are anticipated to have crucial roles in the pathogenesis of TNBC and its therapeutic resistance.
Defective C3d caused by C3 p.W1034R in inherited atypical hemolytic uremic syndrome
Authors: Tsuchida Masafumi , Goto Shin , Watanabe Hirofumi , Goto Sawako , Yamaguchi Hiroki , Narita Ichiei
Published: October 2023

Introduction

Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy. Personal genome analyses have revealed numerous aHUS‐causing variants, mainly complement‐related genes. However, not all aHUS‐causing variants have been functionally validated.

Methods

An exome sequence analysis of a Japanese multiplex family composed of three patients diagnosed with aHUS in infancy and showing frequent relapses clustered in a dominant transmission mode was performed. Protein interaction between the C3d and C‐terminal domains of factor H was analyzed using a quartz crystal microbalance.

Results

Following filtering by heterozygous variants, amino acid substitutions, and allele frequency, the analysis revealed eight rare variants shared by the affected individuals. Variant prioritization listed C3 p.W1034R as the most likely candidate gene mutation in the affected individuals, despite being classified as a variant of uncertain significance. Binding of recombinant C3d harboring 1034R to recombinant short consensus repeats 15 to 20 of factor H was significantly suppressed compared with that of C3 with 1034W.

Conclusion

C3 p.W1034R results in an inherited form of aHUS that often presents with recurrent episodes, possibly because of impaired interactions between the C3d and C‐terminal domains of factor H. Following comprehensive genomic analysis, functional validation of C3 p.W1034R strengthens the molecular basis for aHUS pathophysiology.
Gender‐dependent multiple cross‐phenotype association of interferon lambda genetic variants with peripheral blood profiles in healthy individuals
Authors: Roy Debarati Guha , Singh Lucky , Chaturvedi Himanshu K. , Chinnaswamy Sreedhar
Published: October 2023

Background

Type III interferons (IFN), also called as lambda IFNs (IFN‐λs), are antiviral and immunomodulatory cytokines that are evolutionarily important in humans. Given their central roles in innate immunity, they could be influencing other aspects of human biology. This study aimed to examine the association of genetic variants that control the expression and/or activity of IFN‐λ3 and IFN‐λ4 with multiple phenotypes in blood profiles of healthy individuals.

Methods

In a cohort of about 550 self‐declared healthy individuals, after applying several exclusion criteria to determine their health status, we measured 30 blood parameters, including cellular, biochemical, and metabolic profiles. We genotyped them at rs12979860 and rs28416813 using competitive allele‐specific PCR assays and tested their association with the blood profiles under dominant and recessive models for the minor allele. IFN‐λ4 variants rs368234815 and rs117648444 were also genotyped or inferred.

Results

We saw no association in the combined cohort under either of the models for any of the phenotypes. When we stratified the cohort based on gender, we saw a significant association only in males with monocyte (p = 1 × 10−3) and SGOT (p = 7 × 10−3) levels under the dominant model and with uric acid levels (p = 0.01) under the recessive model. When we tested the IFN‐λ4 activity modifying variant within groupings based on absence or presence of one or two copies of IFN‐λ4 and on different activity levels of IFN‐λ4, we found significant (p < 0.05) association with several phenotypes like monocyte, triglyceride, VLDL, ALP, and uric acid levels, only in males. All the above significant associations did not show any confounding when we tested for the same with up to ten different demographic and lifestyle variables.

Conclusions

These results show that lambda interferons can have pleiotropic effects. However, gender seems to be an effect modifier, with males being more sensitive than females to the effect.
Construction, modeling, and control of a three‐beam prototype using interactive fiber rubber composites
Authors: Acevedo‐Velazquez Aline Iobana , Keshtkar Najmeh , Mersch Johannes , Katzer Konrad , Cherif Chokri , Zimmermann Martina , Gerlach Gerald , Röbenack Klaus
Published: October 2023

In this contribution, we discuss the construction, modeling, and control of a three‐beam prototype that utilizes interactive fiber rubber composites integrated with shape memory alloys (SMAs) as actuators. These actuators are integrated into a textile layer and covered with an elastomer layer, providing flexibility and protection to the prototype. A mathematical model was developed to describe the behavior of the prototype, employing system identification techniques. However, precise position control of systems actuated by SMAs is challenging due to their inherent nonlinearities and hysteretic behavior. To tackle this challenge, a proportional‐integral (PI) controller was designed based on robust stability conditions. The effectiveness of the designed PI controller was validated through both numerical simulations and real experiments.
TRIM28 inactivation in epithelial nephroblastoma is frequent and often associated with predisposing TRIM28 germline variants
Authors: Wegert Jenny , Fischer Anne Kristin , Palhazi Balazs , Treger Taryn D , Hilgers Cäcilia , Ziegler Barbara , Jung Hyunchul , Jüttner Eva , Waha Andreas , Fuchs Jörg , Warmann Steven W , Frühwald Michael C , Hubertus Jochen , Pritchard‐Jones Kathy , Graf Norbert , Behjati Sam , Furtwängler Rhoikos , Gessler Manfred , Vokuhl Christian
Published: October 2023

Wilms tumors (WTs) are histologically diverse childhood cancers with variable contributions of blastema, stroma, and epithelia. A variety of cancer genes operate in WTs, including the tripartite‐motif‐containing‐28 gene (TRIM28). Case reports and small case series suggest that TRIM28 mutations are associated with epithelial morphology and WT predisposition. Here, we systematically investigated the prevalence of TRIM28 inactivation and predisposing mutations in a cohort of 126 WTs with >2/3 epithelial cells, spanning 20 years of biobanking in the German SIOP93‐01/GPOH and SIOP2001/GPOH studies. Overall, 44.4% (56/126) cases exhibited loss of TRIM28 by immunohistochemical staining. Of these, 48 could be further analyzed molecularly, revealing TRIM28 sequence variants in each case – either homozygous (~2/3) or heterozygous with epigenetic silencing of the second allele (~1/3). The majority (80%) of the mutations resulted in premature stops and frameshifts. In addition, we detected missense mutations and small deletions predicted to destabilize the protein through interference with folding of key structural elements such as the zinc‐binding clusters of the RING, B‐box‐2, and PHD domains or the central coiled‐coil region. TRIM28‐mutant tumors otherwise lacked WT‐typical IGF2 alterations or driver events, except for rare TP53 progression events that occurred with expected frequency. Expression profiling identified TRIM28‐mutant tumors as a homogeneous subset of epithelial WTs that mostly present with stage I disease. There was a high prevalence of perilobar nephrogenic rests, putative precursor lesions, that carried the same biallelic TRIM28 alterations in 7/7 cases tested. Importantly, 46% of the TRIM28 mutations were present in blood cells or normal kidney tissue, suggesting germline events or somatic mosaicism, partly supported by family history. Given the high prevalence of predisposing variants in TRIM28‐driven WT, we suggest that immunohistochemical testing of TRIM28 be integrated into diagnostic practice as the management of WT in predisposed children differs from that with sporadic tumors. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Cell‐type‐specific tumour sensitivity identified with a bromodomain targeting PROTAC in adenoid cystic carcinoma
Authors: Rose Alexandra J , Fleming Mercedes M , Francis Jeffrey C , Ning Jian , Patrikeev Anton , Chauhan Ritika , Harrington Kevin J , Swain Amanda
Published: October 2023

Salivary gland adenoid cystic carcinoma (ACC) is a rare malignancy with limited treatment options. The development of novel therapies is hindered by a lack of preclinical models. We have generated ACC patient‐derived xenograft (PDX) lines that retain the physical and genetic properties of the original tumours, including the presence of the common MYB::NFIB or MYBL1::NFIB translocations. We have developed the conditions for the generation of both 2D and 3D tumour organoid patient‐derived ACC models that retain MYB expression and can be used for drug studies. Using these models, we show in vitro and in vivo sensitivity of ACC cells to the bromodomain degrader, dBET6. Molecular studies show a decrease in BRD4 and MYB protein levels and target gene expression with treatment. The most prominent effect of dBET6 on tumours in vivo was a change in the relative composition of ACC cell types expressing either myoepithelial or ductal markers. We show that dBET6 inhibits the progenitor function of ACC cells, particularly in the myoepithelial marker‐expressing population, revealing a cell‐type‐specific sensitivity. These studies uncover a novel mechanistic effect of bromodomain inhibitors on tumours and highlight the need to impact both cell‐type populations for more effective treatments in ACC patients. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
A 500‐kW PV generator I–V curve
Authors: Moretón Rodrigo , Lorenzo Eduardo , Muñoz Javier
Published: October 2023

This paper presents the measurement of the I–V curve of a 500‐kW PV generator by means of an own‐made capacitive load. It is shown that I–V curve analysis can also be applied to big PV generators and that when measuring the operation conditions with reference modules and taking some precautions (especially regarding the operation cell temperature), it is still a useful tool for characterizing them and therefore can be incorporated into maintenance procedures. As far as we know, this is the largest I–V curve measured so far. Copyright © 2013 John Wiley & Sons, Ltd.
Retracing the evolution of a modern periplasmic binding protein
Authors: Michel Florian , Romero‐Romero Sergio , Höcker Birte
Published: October 2023

Investigating the evolution of structural features in modern multidomain proteins helps to understand their immense diversity and functional versatility. The class of periplasmic binding proteins (PBPs) offers an opportunity to interrogate one of the main processes driving diversification: the duplication and fusion of protein sequences to generate new architectures. The symmetry of their two‐lobed topology, their mechanism of binding, and the organization of their operon structure led to the hypothesis that PBPs arose through a duplication and fusion event of a single common ancestor. To investigate this claim, we set out to reverse the evolutionary process and recreate the structural equivalent of a single‐lobed progenitor using ribose‐binding protein (RBP) as our model. We found that this modern PBP can be deconstructed into its lobes, producing two proteins that represent possible progenitor halves. The isolated halves of RBP are well folded and monomeric proteins, albeit with a lower thermostability, and do not retain the original binding function. However, the two entities readily form a heterodimer in vitro and in‐cell. The x‐ray structure of the heterodimer closely resembles the parental protein. Moreover, the binding function is fully regained upon formation of the heterodimer with a ligand affinity similar to that observed in the modern RBP. This highlights how a duplication event could have given rise to a stable and functional PBP‐like fold and provides insights into how more complex functional structures can evolve from simpler molecular components.
Identification of natural Rutaecarpine as a potent tobacco mosaic virus (TMV) helicase candidate for managing intractable plant viral diseases
Authors: Li Zhen‐Xing , Hu Jin‐Hong , Luo Rong‐Shuang , Zhang Tai‐Hong , Ding Yue , Zhou Xiang , Liu Li‐Wei , Wu Zhi‐Bing , Yang Song
Published: October 2023

BACKGROUND

Naturally occurring alkaloids are particularly suitable for use as pesticide precursors and further modifications due to their cost‐effectiveness, unique mechanism of action, tolerable degradation, and environmental friendliness. The famous tobacco mosaic virus (TMV) is a persistent plant pathogenic virus that can parasitize many plants and severely reduce crop production. To treat TMV disease, TMV helicase acts as a crucial target by hydrolyzing adenosine triphosphate (ATP) to provide energy for double‐stranded RNA unwinding.

RESULTS

To seek novel framework alkaloid leads targeting TMV helicase, this work successfully established an efficient screening platform for TMV helicase inhibitors based on natural alkaloids. In vivo activity screening, enzyme activity detection, and binding assays showed that Rutaecarpine from Evodia rutaecarpa (Juss.) Benth exhibited excellent TMV helicase inhibitory properties [dissociation constant (Kd) = 1.1 μm, half maximal inhibitory concentration (IC50) = 227.24 μm] and excellent anti‐TMV ability. Molecular docking and dynamic simulations depicted that Rutaecarpine could stably bind in active pockets of helicase with low binding energy (ΔGbind = −17.8 kcal/mol) driven by hydrogen bonding and hydrophobic interactions.

CONCLUSION

Given Rutaecarpine's laudable bioactivity and structural modifiability, it can serve as a privileged building block for further pesticide discovery.
Evaluation of 30 urban land surface models in the Urban‐PLUMBER project: Phase 1 results
Authors: Lipson Mathew J. , Grimmond Sue , Best Martin , Abramowitz Gab , Coutts Andrew , Tapper Nigel , Baik Jong‐Jin , Beyers Meiring , Blunn Lewis , Boussetta Souhail , Bou‐Zeid Elie , De Kauwe Martin G. , de Munck Cécile , Demuzere Matthias , Fatichi Simone , Fortuniak Krzysztof , Han Beom‐Soon , Hendry Margaret A. , Kikegawa Yukihiro , Kondo Hiroaki , Lee Doo‐Il , Lee Sang‐Hyun , Lemonsu Aude , Machado Tiago , Manoli Gabriele , Martilli Alberto , Masson Valéry , McNorton Joe , Meili Naika , Meyer David , Nice Kerry A. , Oleson Keith W. , Park Seung‐Bu , Roth Michael , Schoetter Robert , Simón‐Moral Andrés , Steeneveld Gert‐Jan , Sun Ting , Takane Yuya , Thatcher Marcus , Tsiringakis Aristofanis , Varentsov Mikhail , Wang Chenghao , Wang Zhi‐Hua , Pitman Andy J.
Published: October 2023

Accurately predicting weather and climate in cities is critical for safeguarding human health and strengthening urban resilience. Multimodel evaluations can lead to model improvements; however, there have been no major intercomparisons of urban‐focussed land surface models in over a decade. Here, in Phase 1 of the Urban‐PLUMBER project, we evaluate the ability of 30 land surface models to simulate surface energy fluxes critical to atmospheric meteorological and air quality simulations. We establish minimum and upper performance expectations for participating models using simple information‐limited models as benchmarks. Compared with the last major model intercomparison at the same site, we find broad improvement in the current cohort's predictions of short‐wave radiation, sensible and latent heat fluxes, but little or no improvement in long‐wave radiation and momentum fluxes. Models with a simple urban representation (e.g., ‘slab’ schemes) generally perform well, particularly when combined with sophisticated hydrological/vegetation models. Some mid‐complexity models (e.g., ‘canyon’ schemes) also perform well, indicating efforts to integrate vegetation and hydrology processes have paid dividends. The most complex models that resolve three‐dimensional interactions between buildings in general did not perform as well as other categories. However, these models also tended to have the simplest representations of hydrology and vegetation. Models without any urban representation (i.e., vegetation‐only land surface models) performed poorly for latent heat fluxes, and reasonably for other energy fluxes at this suburban site. Our analysis identified widespread human errors in initial submissions that substantially affected model performances. Although significant efforts are applied to correct these errors, we conclude that human factors are likely to influence results in this (or any) model intercomparison, particularly where participating scientists have varying experience and first languages. These initial results are for one suburban site, and future phases of Urban‐PLUMBER will evaluate models across 20 sites in different urban and regional climate zones.
Multivariable discrete MPC with exponential cost function on the automation of the anesthesia process
Authors: Sandre‐Hernandez Omar , Ramírez‐Barrios Miguel , Ordaz Patricio , Mera Manuel
Published: October 2023

The automation of the delivery of anesthesia infusion rate in a general medical procedure consists of calculating the adequate infusion to regulate a patient's hypnosis state. In this procedure, the patient model has been considered as a Single‐Input Single‐Output system. However, the anesthesiologist introduces other medications, such as analgesics. Therefore, this contribution considers a closed‐loop formulation with two drugs as input control variables: propofol as an anesthetic, and remifentanil as an analgesic. Then, through the mathematical model description, this paper introduces a multiple‐input and multiple‐output (MIMO) model predictive control (MPC) to regulate the deep of hypnosis (DOH) based on the co‐administration of propofol and remifentanil. Since the control variables must be positive during the procedure, the MPC is formulated as a constrained optimization problem. Quadratic programming solves the optimization problem by designing and developing an exponential cost function, which allows the rapid convergence of the MPC optimization algorithm. Finally, the proposed MPC formulation is tested on 12 patients in silico, simulating a 60‐min general surgery. The simulated results verify the performance of the proposed MPC.
Carbonyl‐Supported Coordination in Imidazolates: A Platform for Designing Porous Nickel‐Based ZIFs as Heterogeneous Catalysts
Authors: Škrjanc Aljaž , Jankovič Dominik , Meden Anton , Mazaj Matjaž , Grape Erik Svensson , Gazvoda Martin , Zabukovec Logar Nataša
Published: October 2023

Zeolitic imidazolate frameworks (ZIFs) are a subclass of metal–organic framework that have attracted considerable attention as potential functional materials due to their high chemical stability and ease of synthesis. ZIFs are usually composed of zinc ions coordinated with imidazole linkers, with some other transition metals, such as Cu(II) and Co(II), also showing potential as ZIF‐forming cations. Despite the importance of nickel in catalysis, no Ni‐based ZIF with permanent porosity is yet reported. It is found that the presence and arrangement of the carbonyl functional groups on the imidazole linker play a crucial role in completing the preferred octahedral coordination of nickel, revealing a promising platform for the rational design of Ni‐based ZIFs for a wide range of catalytic applications. Herein, the synthesis of the first Ni‐based ZIFs is reported and their high potential as heterogeneous catalysts for Suzuki–Miyaura cross‐coupling C─C bond forming reactions is demonstrated.
Carbonaceous Materials‐Based Photothermal Process in Water Treatment: From Originals to Frontier Applications
Authors: Hu Shuyuan , Qin Lei , Yi Huan , Lai Cui , Yang Yang , Li Bisheng , Fu Yukui , Zhang Mingming , Zhou Xuerong
Published: October 2023

The photothermal process has attracted considerable attention in water treatment due to its advantages of low energy consumption and high efficiency. In this respect, photothermal materials play a crucial role in the photothermal process. Particularly, carbonaceous materials have emerged as promising candidates for this process because of exceptional photothermal performance. While previous research on carbonaceous materials has primarily focused on photothermal evaporation and sterilization, there is now a growing interest in exploring the potential of photothermal effect‐assisted advanced oxidation processes (AOPs). However, the underlying mechanism of the photothermal effect assisted by carbonaceous materials remains unclear. This review aims to provide a comprehensive review of the photothermal process of carbonaceous materials in water treatment. It begins by introducing the photothermal properties of carbonaceous materials, followed by a discussion on strategies for enhancing these properties. Then, the application of carbonaceous materials‐based photothermal process for water treatment is summarized. This includes both direct photothermal processes such as photothermal evaporation and sterilization, as well as indirect photothermal processes that assisted AOPs. Meanwhile, various mechanisms assisted by the photothermal effect are summarized. Finally, the challenges and opportunities of using carbonaceous materials‐based photothermal processes for water treatment are proposed.
Survey on security and privacy in Internet of Things‐based eHealth applications: Challenges, architectures, and future directions
Authors: Makina Hela , Letaifa Asma Ben , Rachedi Abderrezak
Published: October 2023

The integration of Internet of Things (IoT) technology into electronic health (eHealth) applications has revolutionized the healthcare landscape, enabling real‐time patient monitoring, personalized care, and improved patient outcomes. However, this convergence of IoT and healthcare also introduces critical security and privacy challenges, needing careful consideration. This survey comprehensively explores the multifaceted realm of security and privacy issues in IoT‐based eHealth applications. First, we taxonomize the diverse security threats that arise due to the interconnected nature of IoT medical devices. Additionally, we highlight privacy concerns stemming from the collection and sharing of personal health information, while reconciling them with the need for accessible and collaborative healthcare ecosystems. Second, we synthesize functional, ethical, and regulatory perspectives to pick up the major requirements needed in the context of eHealth data during their whole lifecycle, from creation to destruction. Third, we identify emerging research strategies employed to address security and privacy concerns, such as cloud‐based solutions, decentralized technologies such as blockchain technology and InterPlanetary File System (IPFS), cryptographic approaches, fine‐grained access control strategies, and so forth. Additionally, we examine the impact of these approaches on computational efficiency, latency, and energy consumption, critically evaluating their suitability in the healthcare context. Building upon this comprehensive assessment, we outline potential future research directions aimed at advancing security and privacy measures in IoT‐based eHealth applications.