bluuebunny/crossref_metadata_2025 huggingface dataset:
Voltammetric approach to measuring free acid in anhydride and ester based on benzoquinone electrochemical reduction
Authors: Liu Yuhong , Lin Mi , Wang Jianguo
Published: December 2023

Free acids commonly exist in anhydride and esters because they are unstable and tend to break down into free acids, which affect the quality of subsequent products in industrial production. Phthalic anhydride and ethyl acetate undergo hydrolysis reactions to form phthalic acid and acetic acid. A differential pulse voltammetry method for the determination of phthalic acid and acetic acid was developed with a bare glassy carbon electrode. Phthalic acid and acetic acid caused a new cathodic peak at more positive potential during the reduction of 1,4‐benzoquinone in acetonitrile or aqueous solution. The new peaks are attributed to the drastic increase in pH at the electrode surface caused by the consumption of protons in the benzoquinone reduction reaction. The peak current of the new cathodic peak was dependent on the concentration of phthalic acid and acetic acid but independent of BQ, phthalic anhydride, and ethyl acetate. This method does not cause hydrolysis of anhydride and ester because no external base is introduced. Furthermore, the method is sensitive, rapid, and does not require pretreatment.
Interpretation of in vitro concentration‐response data for risk assessment and regulatory decision‐making: Report from the 2022 IWGT quantitative analysis expert working group meeting
Authors: Beal Marc A. , Chen Guangchao , Dearfield Kerry L. , Gi Min , Gollapudi Bhaskar , Heflich Robert H. , Horibata Katsuyoshi , Long Alexandra S. , Lovell David P. , Parsons Barbara L. , Pfuhler Stefan , Wills John , Zeller Andreas , Johnson George , White Paul A.
Published: December 2023

Quantitative risk assessments of chemicals are routinely performed using in vivo data from rodents; however, there is growing recognition that non‐animal approaches can be human‐relevant alternatives. There is an urgent need to build confidence in non‐animal alternatives given the international support to reduce the use of animals in toxicity testing where possible. In order for scientists and risk assessors to prepare for this paradigm shift in toxicity assessment, standardization and consensus on in vitro testing strategies and data interpretation will need to be established. To address this issue, an Expert Working Group (EWG) of the 8th International Workshop on Genotoxicity Testing (IWGT) evaluated the utility of quantitative in vitro genotoxicity concentration‐response data for risk assessment. The EWG first evaluated available in vitro methodologies and then examined the variability and maximal response of in vitro tests to estimate biologically relevant values for the critical effect sizes considered adverse or unacceptable. Next, the EWG reviewed the approaches and computational models employed to provide human‐relevant dose context to in vitro data. Lastly, the EWG evaluated risk assessment applications for which in vitro data are ready for use and applications where further work is required. The EWG concluded that in vitro genotoxicity concentration‐response data can be interpreted in a risk assessment context. However, prior to routine use in regulatory settings, further research will be required to address the remaining uncertainties and limitations.
Epileptogenic focal lesions in Dravet syndrome: A warning to investigators
Authors: Ventura Rita , Beltrán‐Corbellini Álvaro , Toledano Rafael , Román Irene Sánchez‐Miranda , García‐Morales Irene , Gil‐Nagel Antonio
Published: December 2023

Objective

Most patients with Dravet syndrome (DS) have unremarkable neuroimaging studies. However, a small number of patients exhibit focal abnormalities that may modify the epilepsy phenotype. We report a case series of DS patients carrying SCN1A variants concurrent with additional focal brain lesions, aiming to provide details regarding their clinical course, electrographic findings, and imaging features.

Methods

We reviewed the electronic medical records of patients with developmental and epileptic encephalopathies in our center, from January 2000 to December 2022, identifying 90 patients with DS resulting from SCN1A variants. Of these, patients displaying focal brain lesions were eligible.

Results

Five patients (4 males and 1 female), with median age of 26 years, were included. All exhibited clinical and electroencephalographic features consistent with the DS spectrum. Sequencing analysis of the SCN1A gene identified pathogenic variants. Magnetic resonance imaging (MRI) revealed focal cortical dysplasia (FCD) in two patients, while the remaining three had cystic lesions. Three patients had previously undergone resective epilepsy surgery in other centers, with no improvement in seizure frequency. Neuropathology studies revealed the presence of FCD type IIA, intracranial teratomas, and dysembryoplastic neuroepithelial tumor (DNET).

Significance

When an individual with an established diagnosis of genetic epilepsy and a focal lesion on MRI is undergoing preoperative evaluation, it is crucial to conduct a comprehensive analysis to understand the relevance of the focal finding for the patient's phenotype and thus anticipate potential surgical outcomes. In instances where epilepsy in DS patients is influenced by a specific focal structural lesion, resective surgery should be carefully considered after precise pharmacological treatment, acknowledging the persistent influence of an SCN1A variant on expected outcomes.
Effects of Tulp4 deficiency on murine embryonic development and adult phenotype
Authors: Jäger Roland , Geyer Stefan H. , Kavirayani Anoop , Kiss Máté G. , Waltenberger Elisabeth , Rülicke Thomas , Binder Christoph J. , Weninger Wolfgang J. , Kralovics Robert
Published: December 2023

Genetically engineered mouse models have the potential to unravel fundamental biological processes and provide mechanistic insights into the pathogenesis of human diseases. We have previously observed that germline genetic variation at the TULP4 locus influences clinical characteristics in patients with myeloproliferative neoplasms. To elucidate the role of TULP4 in pathological and physiological processes in vivo, we generated a Tulp4 knockout mouse model. Systemic Tulp4 deficiency exerted a strong impact on embryonic development in both Tulp4 homozygous null (Tulp4−/−) and heterozygous (Tulp4+/−) knockout mice, the former exhibiting perinatal lethality. High‐resolution episcopic microscopy (HREM) of day 14.5 embryos allowed for the identification of multiple developmental defects in Tulp4−/− mice, including severe heart defects. Moreover, in Tulp4+/− embryos HREM revealed abnormalities of several organ systems, which per se do not affect prenatal or postnatal survival. In adult Tulp4+/− mice, extensive examinations of hematopoietic and cardiovascular features, involving histopathological surveys of multiple tissues as well as blood counts and immunophenotyping, did not provide evidence for anomalies as observed in corresponding embryos. Finally, evaluating a potential obesity‐related phenotype as reported for other TULP family members revealed a trend for increased body weight of Tulp4+/− mice.

Research Highlights

To study the role of the TULP4 gene in vivo, we generated a Tulp4 knockout mouse model.

Correlative analyses involving HREM revealed a strong impact of Tulp4 deficiency on murine embryonic development.
Entrepreneur characteristics and financing patterns in SMES of MENA countries: Overcoming the burdens of liability of newness
Authors: Lassoued Naima , Khanchel Imen , Fakhfakh Imen , Etteyeb Mehdi
Published: December 2023

This study examines the impact of entrepreneur attributes on financing channels of small and medium‐sized enterprises (SMEs) as well as the moderating role of firm age on this relationship. It examines a comprehensive dataset of 4139 firm‐year observations operating in the Middle East and North Africa (MENA) region observed over the 2013–2019 period. The results are four‐fold. First, our overall findings reveal that experienced entrepreneurs tend to use internal funds. Second, the university education of entrepreneurs positively correlates with debt financing. Third, female entrepreneurs are more eager to use internal funds and less debt. Fourth, firm age is found to moderate these relationships. Indeed, in young SMEs, experienced entrepreneurs are shown to rely on debt, graduated entrepreneurs on internal funds, and in older SMEs, female entrepreneurs use debt. Our results bear on the proposals of upper echelons and organizational lifecycle theories.
Diagnostic delay in late‐onset Pompe disease among Chinese patients: A retrospective study
Authors: Yue Dongyue , Jiao Kexin , Xia Xingyu , Zhang Jialong , Zhu Bochen , Liu Lingchun , Du Kunzhao , Gao Mingshi , Cheng Nachuan , Wang Ningning , Luo Sushan , Xi Jianying , Lu Jiahong , Zhao Chongbo , Zhu Wenhua
Published: December 2023

Surveys and retrospective studies have revealed considerable delays in diagnosing late‐onset Pompe disease (LOPD) in China, where the contributing factors remain poorly represented. Our study analyzed the diagnostic journey of 34 LOPD patients seen at our neuromuscular clinic from 2005 to 2022. We defined diagnostic delay as the time from the onset of the first relevant symptoms and laboratory findings suggestive of LOPD to the eventual diagnosis, and we constructed a correlation matrix to assess relationships among these variables. The cohort consisted of 34 patients with an equal male‐to‐female ratio, and the mean age at diagnosis was 27.68 ± 10.03 years. We found the median diagnostic delay to be 5 years, with a range of 0.3 to 20 years, with 97.1% having been misdiagnosed previously, most commonly with “Type II Respiratory insufficiency” (36.7%). Notably, patients at earlier onset (mean age, 18.19 years vs. 31 years; p < 0.005) tended to have higher creatine kinase (CK) levels. Furthermore, 92.6% reported difficulty in sitting up from a supine position since childhood. Our research emphasizes the role of early indicators like dyspnea and difficulty performing sit‐ups in adolescents for timely LOPD diagnosis and treatment initiation. The importance of early high‐risk screening using dried blood spot testing cannot be overstated.
Infusion reactions to adeno‐associated virus (AAV)‐based gene therapy: Mechanisms, diagnostics, treatment and review of the literature
Authors: Notarte Kin Israel , Catahay Jesus Alfonso , Macasaet Raymart , Liu Jin , Velasco Jacqueline Veronica , Peligro Princess Juneire , Vallo Jolaine , Goldrich Nathaniel , Lahoti Lokesh , Zhou Jiayan , Henry Brandon Michael
Published: December 2023

The use of adeno‐associated virus (AAV) vectors in gene therapy has demonstrated great potential in treating genetic disorders. However, infusion‐associated reactions (IARs) pose a significant challenge to the safety and efficacy of AAV‐based gene therapy. This review provides a comprehensive summary of the current understanding of IARs to AAV therapy, including their underlying mechanisms, clinical presentation, and treatment options. Toll‐like receptor activation and subsequent production of pro‐inflammatory cytokines are associated with IARs, stimulating neutralizing antibodies (Nabs) and T‐cell responses that interfere with gene therapy. Risk factors for IARs include high titers of pre‐existing Nabs, previous exposure to AAV, and specific comorbidities. Clinical presentation ranges from mild flu‐like symptoms to severe anaphylaxis and can occur during or after AAV administration. There are no established guidelines for pre‐ and postadministration tests for AAV therapies, and routine laboratory requests are not standardized. Treatment options include corticosteroids, plasmapheresis, and supportive medications such as antihistamines and acetaminophen, but there is no consensus on the route of administration, dosage, and duration. This review highlights the inadequacy of current treatment regimens for IARs and the need for further research to improve the safety and efficacy of AAV‐based gene therapy.
Clinical performance of the STANDARD M10 SARS‐CoV‐2 rapid RT‐PCR assay in patients visiting an emergency department
Authors: Lee Dong‐hyun , Han Eunhee , Ryu Soorack , Choi Hyuk joong , Kim Jieun , Kim Jinyeong , Bae Mi Hyun
Published: December 2023

In emergency departments, rapid screening of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was important for arranging limited isolation resources and patient care during the coronavirus disease 2019 (COVID‐19) pandemic. STANDARD M10 SARS‐CoV‐2 (SD Biosensor) is a recently developed cartridge‐based RT‐PCR that provides a turnaround time of 1 h, which is shorter than that for conventional RT‐PCR. This study evaluated the clinical performance of STANDARD M10 in patients visiting an emergency department. From March to June 2022, two specimens were collected from patients visiting an emergency department. Each specimen comprised one nasopharyngeal and one oropharyngeal swab. Respective specimens underwent rapid RT‐PCR using STANDARD M10 and conventional RT‐PCR using Allplex SARS‐CoV‐2 (Seegene). When discordant results occurred, specimens undergoing the STANDARD M10 were retested with the Allplex to exclude specimen variations. Retest results replaced initial results of the Allplex. Clinical performance of STANDARD M10 was compared with Allplex. The study enrolled 1971 patients. COVID‐19 prevalence was 6.2% based on the Allplex. Compared with the Allplex, overall agreement, positive percent agreement, and negative percent agreement of STANDARD M10 were 99.5% (95% CI: 99.1%–99.8%), 95.9% (95% CI: 90.8%–98.3%), and 99.8% (95% CI: 99.4%–99.9%), respectively. Nine discordant results were all positive on droplet digital PCR, except for one specimen that was positive with STANDARD M10. The STANDARD M10 showed reliable diagnostic performance for detecting SARS‐CoV‐2 from patients visiting in emergency departments and is a useful tool in emergency healthcare systems because of its easy‐to‐use cartridge‐based assay and short resulting time for detecting SARS‐CoV‐2.
The International Human Papillomavirus Reference Center: Standardization, collaboration, and quality assurance in HPV research and diagnostics
Authors: Arroyo Mühr Laila Sara , Lagheden Camilla , Hassan Sadaf S. , Eklund Carina , Dillner Joakim
Published: December 2023

The International Human Papillomavirus (HPV) Reference Center (IHRC) confirms and assigns type numbers to novel HPV types, maintains a reference clone repository, and issues international proficiency panels for HPV screening and genotyping. Furthermore, the Center coordinates the Global HPV Reference Laboratory Network that promotes collaboration and international exchange of experiences among national HPV reference laboratories, to further international standardization and quality assurance in the HPV field. The established HPV types (n = 225) belong to 5 different genera: alpha (n = 65), beta (n = 54), gamma (n = 102), mu (n = 3) and nu (n = 1). Since the last published IHRC overview in 2018, 6 novel types have been established, with 5/6 belonging to the gamma genus and 1/6 to beta genus. Also, 474 reference clones have been provided to 55 different research laboratories and the global proficiency program for HPV genotyping has seen an increasing proficiency (despite a decrease seen in 2019), from 68% proficiency in 2017 to 77.3% in 2022. The first proficiency study for HPV screening found an international proficiency of up to 77%. In summary, increasing complexity of the HPVs and demands on quality assurance in the era of cervical cancer elimination requires international efforts to support proficiency and recognized quality and order among HPV types.
Investigating the effects of zinc oxide and titanium dioxide nanoparticles on the formation of biofilm and persister cells in Klebsiella pneumoniae
Authors: Pourmehdiabadi Aisouda , Nobakht Mojgan Sarabi , Hajjam Balajorshari Behdad , Yazdi Mohammadreza Rezaei , Amini Kumarss
Published: December 2023

The biofilm formation in klebsiella pneumoniae isolates poses a significant problem as it can result in treatment failure and the development of chronic infections. These biofilms act as protective barriers, rendering the bacteria resistant to antibiotics. Additionally, persister cells, which make up a small fraction of the bacterial population, have the ability to enter a dormant state after treatment with high doses of antibiotics. These persister cells play a crucial role in the high level of biofilm‐mediated tolerance to antibiotics. The present study aimed to investigate the impact of Zinc oxide (ZnO) and titanium dioxide (TiO2) nanoparticles on the formation of biofilm and persister cells in K. pneumoniae. The minimum inhibitory concentration (MIC) of colistin in K. pneumoniae ATCC 13883 was determined using the microdilution method. The formation of persister cells was evaluated by introducing sub‐MIC of colistin. Subsequently, the MIC of ZnO NPs and TiO2 NPs in these persister cells was assessed using the microdilution method. Furthermore, the effects of nanoparticles on the expression levels of biofilm‐associated genes were analyzed using real‐time polymer chain reaction (PCR). The MIC values for colistin, ZnO, and TiO2 were determined at 2, 12.5, and 6.25 μg/mL, respectively. In the presence of nanoparticles, biofilm formation decreased. Real‐time PCR results showed the messenger RNA (mRNA) level of mrkH and fimH were decreased and the expression of luxS and mazF were increased. Biofilm formation of K. pneumoniae ATCC 1383 was inhibited in response to nanoparticles. According to the results of the present study use of nanoparticles may help control multidrug‐resistant (MDR) infections in hospitalized patients.
Creative Subprocess Frequencies and Their Relation to Personal Characteristics and Product Creativity: Insights from a Drawing Task Think Aloud Study
Authors: Boldt Gregory T. , Kaufman James C.
Published: December 2023

Most research on the creative process has focused on idea generation, and the prevalence and influence of many other creative subprocesses remain poorly understood. To clarify different subprocesses' respective roles in creative work, this study investigated their frequencies and associations with creativity‐related personal characteristics and product creativity. Undergraduate students (n = 266) articulated their creative thought processes via the think aloud method while completing an open‐ended drawing task and completed questionnaires assessing creativity‐relevant personal characteristics. Drawings were rated for creativity by quasi‐expert judges. Transcripts were coded using an a priori coding scheme informed by models of the creative process, including generation (14%), elaboration (26%), association (9%), selection (4%), evaluation (13%), anchoring (13%), metacognition (7%), and filler (14%). Subprocess frequencies correlated minimally with measures of personal characteristics, although several significant, albeit weak, relationships emerged. A hierarchical regression analysis indicated that the best predictors of drawing creativity were aesthetic fluency, the frequency of anchoring, time spent on task, and, marginally, the frequency of generation. Together, these results provide insight into how relevant personal characteristics and subprocess engagement contribute to drawing creativity and highlight the particular importance of anchoring, which involves monitoring and refining task‐related goals and constraints, throughout the creative process.
Rapid deglaciation of the La Vega gorge (Sierra de Gredos, Iberian Peninsula) at the end of the global Last Glacial Maximum
Authors: Alcalá‐Reygosa Jesús , Campos Néstor , Schimmelpfennig Irene , Sanjurjo‐Sánchez Jorge , Léanni Laetitia , Zamorano José Juan ,   ASTER Team
Published: December 2023

Previous studies from the Iberian Central System and other mountains of the Iberian Peninsula and Europe suggest that deglaciation in this area occurred at the end or immediately after the global Last Glacial Maximum (LGM, 26.5–19 ka). In this research, we investigate the timing and speed of deglaciation of the palaeoglacier in La Vega gorge (Iberian Central system) since the global LGM, dating the outer moraines, glacially polished bedrock and glaciofluvial deposits by means of in situ cosmogenic 10Be and optically stimulated luminescence. The results show that one intermediate arc located at the outer frontal moraine system has an age of ~21 ka, being consistent with the global LGM. Deglaciation began at ~21–19 ka, speeding up at ~19 ka. We estimate that around 4–5 km of the palaeoglacier receded in ~1–2 kyrs since ~19 ka, leaving La Vega gorge probably ice‐free at ~18 ka. Therefore, our data confirm that deglaciation in Sierra de Gredos began at the end of the global LGM, characterised by a rapid and massive retreat of glaciers.
Can we let our patients sleep in the hospital? A randomized controlled trial of a pragmatic sleep protocol in surgical oncology patients
Authors: Kelly Kathrine , Kolbeinsson Hordur , Blanck Lauren M. , Khan Mariam , Kyriakakis Roxanne , Assifi M. Mura , Wright G. Paul , Chung Mathew
Published: December 2023

Background

Postoperative inpatients experience increased stress due to pain and poor restorative sleep than non‐surgical inpatients.

Objectives and Methods

A total of 101 patients, undergoing major oncologic surgery, were randomized to a postoperative sleep protocol (n = 50) or standard postoperative care (n = 51), between August 2020 and November 2021. The primary endpoint of the study was postoperative sleep time after major oncologic surgery. Sleep time and steps were measured using a Fitbit Charge 4®.

Results

There was no statistically significant difference found in postoperative sleep time between the sleep protocol and standard group (median sleep time of 427 min vs. 402 min; p = 0.852, respectively). Major complication rates were similar in both groups (7.4% vs. 8.9%). Multivariate analysis found sex and Charlson Comorbidity Index to be significant factors affecting postoperative sleep time and step count. Postoperative delirium was only observed in the standard group, although this did not reach statistical significance. There were no in hospital mortalities.

Conclusion

The use of a sleep protocol was found to be safe in our study population. There was no statistical difference in postoperative sleep time or major complications. Institution of a more humane sleep protocol for postoperative inpatients should be considered.
Controllable Wrinkling Inspired Multifunctional Metamaterial for Near‐Field and Holographic Displays
Authors: Han Donghai , Li Wenkang , Hou Yushan , Chen Xiaoming , Shi Hongyu , Meng Fanqi , Zhang Liuyang , Chen Xuefeng
Published: December 2023

Tunable electromagnetic (EM) metamaterials have received significant attention due to their compelling advantages of integration and minimization compared with conventional bulky devices. Meanwhile, mechanically reconfigurable metamaterials have witnessed a striving period over recent years due to their simplified structural composition and confined modulation capabilities. Here, a controllable‐wrinkling‐based reconfiguration method is proposed to design split‐ring resonant units with dynamic transmittance spectra by switching between planar and wrinkling morphologies. For the linear polarized incidence, the geometries of planar and wrinkled units are optimized to achieve on‐demanded manipulation of the phases and amplitudes, respectively. By simultaneously implementing the amplitude design and the phase gradient, the mechanically inspired metamaterial is engineered to display a near‐field and a holographic image. For circularly polarized incidences, the spin‐decoupled phases and chiral effects demonstrated in the planar and wrinkled state assist in designing a metamaterial to possess spin‐multiplexed and strain‐modulated fourfold displays. These results demonstrate the practical feasibility of the wrinkling method in engineering tunable metamaterials, and the design flexibility, as well as the mechanical strategy, can extend the potential toward the application scenarios such as information processing, sensing, imaging, flexible meta‐devices, etc.
Dark Current Mechanisms and Suppression Strategies for Infrared Photodetectors Based on Two‐Dimensional Materials
Authors: Zhang Xinlei , Li Ruizhi , Yu Yuanfang , Dai Fuxing , Jiang Ruiqi , Guo Jiaxiang , Hu Weida , Ni Zhenhua , Lu Junpeng
Published: December 2023

Narrow‐bandgap 2D materials and semimetals, for example, graphene, black phosphorus (BP), tellurium (Te), and some novel transition metal dichalcogenides (TMDs), have been demonstrated to be promising building blocks for constructing next‐generation state‐of‐the‐art infrared (IR) photodetectors. However, these devices suffer from a significant dark current, primarily attributed to the intrinsic thermal excitation‐induced high carrier concentration. Suppressing the dark current is an essential issue in pursuing higher specific detectivity of IR photodetectors. Here, the authors demonstrate recent advances in suppressing dark current for 2D IR photodetectors. First, a brief insight into the dark current composition and mechanisms of 2D IR photodetectors is illustrated. Then, the varied band alignment for blocking dark current by the interfacial barrier is discussed. Next, localized electric field modulation by applying a gate voltage and ferroelectric materials is discussed. This method can effectively tune the concentration and distribution of carriers in the device conductive channel. Following that, interfacial engineering is summarized, by which interfacial defects can be passivated and interlayer defect‐induced dark current can be suppressed. Finally, the challenges and an outlook are delivered for developing state‐of‐the‐art IR photodetectors.
Celebrity co‐creator or celebrity endorser? Exploring mediating and moderating factors in Marcom decision
Authors: Roy Subhadip , Mishra Aditya Shankar , Bailey Ainsworth Anthony
Published: December 2023

The present research delves into the concept of celebrity co‐creation from the consumer behavior perspective. It explores the impact of the degree of a celebrity's involvement with a brand (celebrity as an endorser vs. celebrity as a co‐creator) on consumers' advertisement and brand‐based evaluations (Study 1) and purchase behavior (Study 2). The research subsequently incorporates the mediating effects of consumers' perceived risk (Study 3) and the moderating effect of celebrity expertise (Study 4) in the relationships. Three of the four studies were controlled experiments among nonstudent samples (combined n = 486), while one was a field study. Major findings indicate that a celebrity co‐creator is more effective than a celebrity endorser, but both cases of celebrity presence are more effective than the control (Studies 1 and 2). This effect is observed to be mediated by the consumers' perceived risk (Study 3) and moderated by the celebrity's expertise (Study 4). The present research provides a new direction to value co‐creation research from the communications perspective and adds to the literature on celebrity endorsements.
Another step forward for neuromuscular ultrasound
Authors: Caress James B. , Wiesler Ethan R.
Published: December 2023

See article on pages 295–302 in this issue.
A rapid method for phosphocreatine‐weighted imaging in muscle using double saturation power‐chemical exchange saturation transfer
Authors: Viswanathan Malvika , Kurmi Yashwant , Zu Zhongliang
Published: December 2023

Monitoring the variation in phosphocreatine (PCr) levels following exercise provides valuable insights into muscle function. Chemical exchange saturation transfer (CEST) has emerged as a sensitive method with which to measure PCr levels in muscle, surpassing conventional MR spectroscopy. However, existing approaches for quantifying PCr CEST signals rely on time‐consuming fitting methods that require the acquisition of the entire or a section of the CEST Z‐spectrum. Additionally, traditional fitting methods often necessitate clear CEST peaks, which may be challenging to obtain at low magnetic fields. This paper evaluated the application of a new model‐free method using double saturation power (DSP), termed DSP‐CEST, to estimate the PCr CEST signal in muscle. The DSP‐CEST method requires the acquisition of only two or a few CEST signals at the PCr frequency offset with two different saturation powers, enabling rapid dynamic imaging. Additionally, the DSP‐CEST approach inherently eliminates confounding signals, offering enhanced robustness compared with fitting methods. Furthermore, DSP‐CEST does not demand clear CEST peaks, making it suitable for low‐field applications. We evaluated the capability of DSP‐CEST to enhance the specificity of PCr CEST imaging through simulations and experiments on muscle tissue phantoms at 4.7 T. Furthermore, we applied DSP‐CEST to animal leg muscle both before and after euthanasia and observed successful reduction of confounding signals. The DSP‐CEST signal still has contaminations from a residual magnetization transfer (MT) effect and an aromatic nuclear Overhauser enhancement effect, and thus only provides a PCr‐weighted imaging. The residual MT effect can be reduced by a subtraction of DSP‐CEST signals at 2.6 and 5 ppm. Results show that the residual MT‐corrected DSP‐CEST signal at 2.6 ppm has significant variation in postmortem tissues. By contrast, both the CEST signal at 2.6 ppm and a conventional Lorentzian difference analysis of CEST signal at 2.6 ppm demonstrate no significant variation in postmortem tissues.
Study of impact performance of composite sandwich structure fabricated partially with natural fiber facesheet
Authors: Ashraf Waqas , Ishak Mohamad Ridzwan , Khan Tabrej , Sebaey Tamer A. , Singh Balbir , Alshahrani Hassan
Published: December 2023

Composite structures with a pure glass composite facesheet and an aluminum honeycomb core are widely used in aircraft interiors. Because impact‐related problems are related to structural integrity and safety performance, the behavior of these structures under impact loading is critical. Due to their promising performance, lower cost, and low environmental impact, hybrid composites have recently become one of the most widely researched composite materials in the research field. This paper aims to investigate the impact behavior of nonhybrid glass and the glass partially replaced with a flax and kenaf hybrid composite facesheet caused by a low‐velocity impact. The specimens were impacted with different impacted energies, such as 10, 20, and 30 J. All nonimpacted and impacted samples were tested and compared for postimpact flexural (three‐point bending) behavior to analyze the residual strength of sandwich structures after impact. The results revealed that the hybrid composite face sheet outperformed the glass composite sandwich structure. The hybrid composite face sheet allowed the impactor to penetrate deeper, resulting in better energy absorption than the glass composite. Compared to nonimpacted specimens, the glass and hybrid face sheet combinations demonstrated comparable residual bending performance.

Highlights

Experimental analysis shows the impact resistance (low‐velocity impact test) and residual load‐carrying capacity (three‐point bending test) of glass and hybrid composite face sheets.

Hybrid face sheets show excellent energy‐absorbing capability compared to glass one.

The residual flexural strength of the glass and hybrid composites was comparable to that of nonimpacted samples.

The peel strength achieved in this study using the pre‐cure fabrication process was significantly higher than the peel strength achieved using prepreg face sheets.

Reinforcing the composite face sheet of the sandwich structure by partially replacing the glass with flax and kenaf fiber exhibited comparable performance.
Randomized controlled trial of an individual blended cognitive behavioral therapy to reduce psychological distress among distressed colorectal cancer survivors: The COloRectal canceR distrEss reduCTion trial
Authors: Custers José A. E. , Kwakkenbos Linda , Levis Brooke , Döking Sarah , van der Hoeven Yvonne C. W. , Leermakers Lynn , de Wilt Johannes H. W. , Thewes Belinda , Braamse Annemarie M. J. , Dekker Joost , Prins Judith B.
Published: December 2023

Objective

Colorectal cancer survivors (CRCS) often experience high levels of distress. The objective of this randomized controlled trial was to evaluate the effect of blended cognitive behavior therapy (bCBT) on distress severity among distressed CRCS.

Methods

CRCS (targeted N = 160) with high distress (Distress Thermometer ≥5) between 6 months and 5 years post cancer treatment were randomly allocated (1:1 ratio) to receive bCBT, (14 weeks including five face‐to‐face, and three telephone sessions and access to interactive website), or care as usual (CAU). Participants completed questionnaires at baseline (T0), four (T1) and 7 months later (T2). Intervention participants completed bCBT between T0 and T1. The primary outcome analyzed in the intention‐to‐treat population was distress severity (Brief Symptom Inventory; BSI‐18) immediately post‐intervention (T1).

Results

84 participants were randomized to bCBT (n = 41) or CAU (n = 43). In intention‐to‐treat analysis, the intervention significantly reduced distress immediately post‐intervention (−3.86 points, 95% CI −7.00 to −0.73) and at 7 months post‐randomization (−3.88 points, 95% CI −6.95 to −0.80) for intervention compared to CAU. Among secondary outcomes, at both time points, depression symptoms, anxiety symptoms, cancer worry, and cancer‐specific distress were significantly lower in the intervention arm. Self‐efficacy scores were significantly higher. Overall treatment satisfaction was high (7.4/10, N = 36) and 94% of participants would recommend the intervention to other colorectal cancer patients.

Conclusions

The blended COloRectal canceR distrEss reduCTion intervention seems an efficacious psychological intervention to reduce distress severity in distressed CRCS. Yet uncertainty remains about effectiveness because fewer participants than targeted were included in this trial.

Trial Registration

Netherlands Trial Register NTR6025.
Calculating intrinsic positive end‐expiratory pressure from end‐expiratory flow in mechanically ventilated children—A study in physical models of the pediatric respiratory system
Authors: Schumann Stefan , Ucar Sascha , Wenzel Christin , Spaeth Johannes
Published: December 2023

Rationale

The high resistance of pediatric endotracheal tubes (ETTs) exposes mechanically ventilated children to a particular risk of developing intrinsic positive end‐expiratory pressure (iPEEP). To date, determining iPEEP at the bedside requires the execution of special maneuvers, interruption of ventilation, or additional invasive measurements. Outside such interventions, iPEEP may be unrecognized.

Objective

To develop a new approach for continuous calculation of iPEEP based on routinely measured end‐expiratory flow and ETT resistance.

Methods

First, the resistance of pediatric ETTs with inner diameter from 2.0 to 4.5 mm were empirically determined. Second, during simulated ventilation, iPEEP was either calculated from the measured end‐expiratory flow and ETT's resistance (iPEEPcalc) or determined with a hold‐maneuver available at the ventilator (iPEEPhold). Both estimates were compared with the end‐expiratory pressure measured at the ETT's tip (iPEEPdirect) by means of absolute deviations.

Results

End‐expiratory flow and iPEEP increased with decreasing ETT inner diameter and with higher respiratory rates. iPEEPcalc and iPEEPhold were comparable and indicated good correspondence with iPEEPdirect. The largest absolute mean deviation was 1.0 cm H2O for iPEEPcalc and 1.1 cm H2O for iPEEPhold.

Conclusion

We conclude that iPEEP can be determined from routinely measured variables and predetermined ETT resistance, which has to be confirmed in the clinical settings. As long as this algorithm is not available in pediatric ICU ventilators, nomograms are provided for estimating the prevailing iPEEP from end‐expiratory flow.
TATB thermal decomposition: An improved kinetic model for explosive safety analysis
Authors: Moore Jason S. , Morrison Keith D. , Burnham Alan K. , Racoveanu Ana , Reynolds John G. , Koroglu Batikan , Coffee Keith R. , Klunder Greg L.
Published: December 2023

We investigate and model the cook‐off behavior of 1,3,5‐triamino‐2,4,6‐trinitrobenzene (TATB) to understand the response of explosive systems in abnormal thermal environments. Decomposition has been explored via conventional ODTX (one‐dimensional time‐to‐explosion), PODTX (ODTX with pressure‐measurement), PyGC‐MS (pyrolysis gas chromatography mass spectrometry), TGA (thermo‐gravimetric analysis), DSC (differential scanning calorimetry), and IR (infrared spectroscopy) experiments under isothermal and ramped temperature profiles. The data were used to fit rate parameters for proposed reaction schemes in a MATLAB thermo‐chemical computational model. These parameterizations were carried out utilizing a genetic algorithm optimization method on LLNL's high‐performance computing clusters, which enabled significant parallelization. These results include a multi‐step reaction decomposition model, identification of likely autocatalytic gas‐phase species, accurate high‐temperature sensitization, and prediction of confined system pressurization. This model will be scalable to several applications involving TATB‐based explosives, like LX‐17, including thermal safety models of full‐scale systems.
4‐Thiaproline accelerates the slow folding phase of proteins containing cis prolines in the native state by two orders of magnitude
Authors: Loughlin Jennie O' , Zinovjev Kirill , Napolitano Silvia , van der Kamp Marc , Rubini Marina
Published: December 2023

The cis/trans isomerization of peptidyl‐prolyl peptide bonds is often the bottleneck of the refolding reaction for proteins containing cis proline residues in the native state. Proline (Pro) analogues, especially C4‐substituted fluoroprolines, have been widely used in protein engineering to enhance the thermodynamic stability of peptides and proteins and to investigate folding kinetics. 4‐thiaproline (Thp) has been shown to bias the ring pucker of Pro, to increase the cis population percentage of model peptides in comparison to Pro, and to diminish the activation energy barrier for the cis/trans isomerization reaction. Despite its intriguing properties, Thp has been seldom incorporated into proteins. Moreover, the impact of Thp on the folding kinetics of globular proteins has never been reported. In this study, we show that upon incorporation of Thp at cisPro76 into the thioredoxin variant Trx1P the half‐life of the refolding reaction decreased from ~2 h to ~35 s. A dramatic acceleration of the refolding rate could be observed also for the protein pseudo wild‐type barstar upon replacement of cisPro48 with Thp. Quantum chemical calculations suggested that the replacement of the CγH2 group by a sulfur atom in the pyrrolidine ring, might lower the barrier for cis/trans rotation due to a weakened peptide bond. The protein variants retained their thermodynamic stability upon incorporation of Thp, while the catalytic and enzymatic activities of the modified Trx1P remained unchanged. Our results show that the Pro isostere Thp might accelerate the rate of the slow refolding reaction for proteins containing cis proline residues in the native state, independent from the local structural environment.
Hydrophobicity: The door to drug delivery
Authors: Falanga Annarita , Bellavita Rosa , Braccia Simone , Galdiero Stefania
Published: December 2023

The engineering of intracellular delivery systems with the goal of achieving personalized medicine has been encouraged by advances in nanomaterial science as well as a greater understanding of diseases and of the biochemical pathways implicated in many disorders. The development of vectors able to transport the drug to a target location and release it only on demand is undoubtedly the primary issue. From a molecular perspective, the topography of drug carrier surfaces is directly related to the design of an effective drug carrier because it provides a physical hint to modifying its interactions with biological systems. For instance, the initial ratio of hydrophilic to hydrophobic surfaces and the changes brought about by external factors enable the release or encapsulation of a therapeutic molecule and the ability of the nanosystem to cross biological barriers and reach its target without causing systemic toxicity. The first step in creating new materials with enhanced functionality is to comprehend and characterize the interplay between hydrophilic and hydrophobic molecules at the molecular level. Therefore, the focus of this review is on the function of hydrophobicity, which is essential for matching the complexity of biological environments with the intended functionality.
Explaining heatwaves with machine learning
Authors: Buschow Sebastian , Keller Jan , Wahl Sabrina
Published: December 2023

Heatwaves are known to arise from the interplay between large‐scale climate variability, synoptic weather patterns, and regional to local‐scale surface processes. Though recent research has made important progress for each individual contributing factor, ways to properly incorporate multiple or all of them in a unified analysis are still lacking. In this study, we consider a wide range of possible predictor variables from the ERA5 Reanalysis version 5 and ask how much information on heatwave occurrence in Europe can be learned from each of them. To simplify the problem, we first adapt the recently developed logistic principal component analysis to the task of compressing large binary heatwave fields to a small number of interpretable principal components. The relationships between heatwaves and various climate variables can then be learned by a neural network. Starting from the simple notion that the importance of a variable is given by its impact on the performance of our statistical model, we arrive naturally at the definition of Shapley values. Classic results of game theory show that this is the only fair way of distributing the overall success of a model among its inputs. We find a nonlinear model that explains 70% of reduced heatwave variability. The biggest individual contribution (27% of the 70%) comes from upper level geopotential; top‐level soil moisture is in second place (15%). Beyond this decomposition, Shapley interaction values enable us to quantify overlapping information and positive synergies between all pairs of predictors.
Decomposing (n+1)$(n+1)$‐Qubit Toffoli Gate with Shallow Circuit Depth and No Ancilla
Authors: Leng Jian , Yang Fan , Wang Xiang‐Bin
Published: December 2023

Circuit depth optimization is crucial for implementing quantum algorithms in practical systems. The decomposition of ‐qubit Toffoli gate is continually optimized since this gate is a fundamental component for many quantum algorithms. Without any ancilla, ‐qubit Toffoli gate can be decomposed by standard gates with circuit depth . Here, the decomposition is further optimized and its circuit depth is reduced to . The decomposition is equivalent to ‐qubit Toffoli gate up to an overall phase and also does not need any ancilla.
How infrastructure development, technological innovation, and institutional quality impact the environmental quality of G7 countries: A step towards environmental sustainability
Authors: Zaman Badee Uz , Yu Hui‐Yun
Published: December 2023

Despite the economic success, the G7 nations have not adequately prioritized environmental welfare. However, these nations must recognize that economic prosperity cannot be sustained without safeguarding environmental sustainability. In short, environmental protection is a necessary component of achieving sustainable development goals. For this matter, this study aims to analyze the effects of accumulative infrastructure development, economic growth, foreign direct investment, technological innovation, and institutional quality on the CO2 emissions of the G7 countries. Using annual panel data from 1996 to 2020, this study employs cross‐sectional autoregressive distributed lags (CS‐ARDL) to determine the environmental impacts of the variables under investigation. The findings show that foreign direct investment and institutional quality have a favorable effect and improve environmental quality. In contrast, the accumulative (transport, energy, financial, and information and communication [ICT]) infrastructure development, economic growth, and technological innovation stimulate environmental degradation by increasing CO2 emissions. These results are found robust, as validated by the Common Correlated Effect Mean Group (CCEMG). In line with these crucial findings, governments have suggested that specific measures supporting innovation in environmental‐related technologies, infrastructure development, and economic growth must be implemented to mitigate CO2 emissions in the G7 countries.
Planning stepped wedge cluster randomized trials to detect treatment effect heterogeneity
Authors: Li Fan , Chen Xinyuan , Tian Zizhong , Wang Rui , Heagerty Patrick J.
Published: December 2023

Stepped wedge design is a popular research design that enables a rigorous evaluation of candidate interventions by using a staggered cluster randomization strategy. While analytical methods were developed for designing stepped wedge trials, the prior focus has been solely on testing for the average treatment effect. With a growing interest on formal evaluation of the heterogeneity of treatment effects across patient subpopulations, trial planning efforts need appropriate methods to accurately identify sample sizes or design configurations that can generate evidence for both the average treatment effect and variations in subgroup treatment effects. To fill in that important gap, this article derives novel variance formulas for confirmatory analyses of treatment effect heterogeneity, that are applicable to both cross‐sectional and closed‐cohort stepped wedge designs. We additionally point out that the same framework can be used for more efficient average treatment effect analyses via covariate adjustment, and allows the use of familiar power formulas for average treatment effect analyses to proceed. Our results further sheds light on optimal design allocations of clusters to maximize the weighted precision for assessing both the average and heterogeneous treatment effects. We apply the new methods to the Lumbar Imaging with Reporting of Epidemiology Trial, and carry out a simulation study to validate our new methods.
Gauging the Aromatic, Antiaromatic, and Nonaromatic Character of the Dications and Dianions Derived from Fused Carbocyclic and Heterocyclic Compoundsǂ
Authors: Borosky Gabriela L. , Laali Kenneth K.
Published: December 2023

Dications and dianions derived from fused PAHs and hetero‐PAHs were investigated by means of DFT calculations. The electronic, energetic, and structural features of the singlet and triplet electronic states of these doubly charged species were computationally determined and compared with those of the corresponding neutral parent aromatic and heteroaromatic compounds. The aromatic, nonaromatic or antiaromatic character of the studied diions was evaluated via magnetic criteria, namely NICS and 1H NMR chemical shifts, and by the HOMA structural index. Linear correlations were revealed between the computed HOMO‐LUMO gaps and the magnetic parameters which could serve as a guiding tool in the modulation of molecular properties, and for designing new materials derived from this type of compounds.
MeOH‐Mediated Efficient Reduction with N‐Heterocyclic Carbene Boranes Towards the Synthesis of Cyclic Sulfamates and Sulfonamides
Authors: Zheng Hao , Song Qing‐Chun , Guan Zi‐Wen , Li Zhang‐Rui , Chen Ling‐Yan , Li Ya
Published: December 2023

An efficient approach for the reduction of cyclic N‐sulfonylimines using N‐heterocyclic carbene boranes as the hydride donor was developed, leading to various cyclic sulfamates and sulfonamides in excellent yields. The approach had broad scope including both the N‐sulfonyl aldimines and ketimines under mild reaction conditions, which proves that the NHC‐boranes are good alternatives as the reductive reagents.