bluuebunny/crossref_metadata_2025 huggingface dataset:
Predominant landward skewing of tidal meanders
Authors: Gao Chao , Finotello Alvise , Wang Ya Ping
Published: July 2022

Highly sinuous, high‐amplitude meander bends shaped by unidirectional, downstream‐oriented flows in alluvial rivers are predominantly upstream‐skewed, offering an opportunity to infer flow direction from meander planforms. In contrast, it remains unclear whether tidal meander bends formed by bidirectional, potentially asymmetric flows display similar skewing preferences, despite being characterized by planform dynamics similar to their alluvial counterparts. Geomorphological characteristics of meandering channels in different tidal environments thus merit further research. Here we used satellite images to measure meandering patterns for 232 purely tidal channels located at 25 study sites worldwide, to disclose imprints of tidal flows embedded in meander planforms. Our study sites span micro‐ to macro‐tidal settings characterized by different tidal flow asymmetries, and include both vegetated mangrove swamps and salt marshes, as well as unvegetated intertidal flats. We found that tidal meanders exhibit morphological features consistently scaled to local channel width regardless of tidal regimes, and that they are typically less sinuous than fluvial bends. Exponential landward reduction of channel widths (i.e. funnelling) is counterbalanced by a linear increase in width‐adjusted bend amplitude that is more pronounced in ebb‐dominated environments. More importantly, the majority of tidal bends appear to be preferentially landward‐skewed, and the degree of skewing increases as bend sinuosity and amplitude increase as well. Although the mechanism controlling such skewing preference remains elusive and further fieldwork is needed to elucidate this point, we hypothesize that it might be related to the local dominance of ebb flows characterizing most tidal environments. Overall, our results demonstrate a statistical preference for landward skewing in high‐amplitude, highly sinuous tidal meander bends that does not depend on the site‐specific characteristics of the considered tidal environment and can be potentially employed to infer the direction of tidal flows based exclusively on remotely sensed meander planforms.
Spatial variability of runoff recharge sources and influence mechanisms in an arid mountain flow‐producing zone
Authors: Sang Liyuan , Zhu Guofeng , Qiu Dongdong , Zhang Zhuanxia , Liu Yuwei , Zhao Kailiang , Wang Lei , Sun Zhigang
Published: July 2022

In‐depth knowledge of the hydrological conditions of basins in arid regions can help to maintain the long‐term water security. The mechanisms of runoff generation and flow paths in different landscape areas are not fully known due to spatial variability. We have explored the mechanisms by which spatial variability affects the runoff recharge sources in the Xiying River Basin. The results showed that the spatial variability of the sources and generation mechanisms of runoff in the arid mountain flow‐producing zone is the result of the combined effect of different landscape, elevation and meteorological elements. In the upstream area, the short mean transit time (MTT) combined with the high contribution of recharge from the meltwater (29.32%) and the proportion of pre‐event water (between 60% and 90%) means that runoff production processes are strongly controlled by meltwater recharge and precipitation events. The MTT and the proportion of pre‐event water in the midstream area are ranked in the middle of the three landscape areas, but the highest contribution of precipitation (16.57%) indicates the importance of precipitation to runoff production processes. In the downstream area, the MTT is the longest and the proportion of pre‐event water is the smallest, and groundwater remains the basis for long‐term stability of runoff (groundwater contribution rate: 40.62%). By enhancing the spatial resolution for identifying runoff recharge sources can reduce the model uncertainty by 69%. Thus, taking full account of the spatial heterogeneity in arid regions is an important initiative to achieve scientific water resources management.
“Let Me Just Close My Eyes”: Challenged and Banned Books, Claimed Identities, and Comics
Authors: Dallacqua Ashley K.
Published: July 2022

This column centers around the voices of two AP English students as a way to consider the current book challenging and banning occurring throughout the United States. The column reviews the 2021 year of book challenges in the news and media, students' own perceptions of these bans, with a focus on comics. Finally, there are suggestions and reviews of policies in support of diverse texts in schools and libraries.
Comparison of decellularization protocols for cultured cell‐derived extracellular matrix—Effects on decellularization efficacy, extracellular matrix retention, and cell functions
Authors: Hoshiba Takashi , Yunoki Shunji
Published: July 2022

The in vitro reconstruction of the extracellular matrix (ECM) is required in tissue engineering and regenerative medicine because the ECM can regulate cell functions in vivo. For ECM reconstruction, a decellularization technique is used. ECM reconstructed by decellularization (dECM) is prepared from tissues/organs and cultured cells. Although decellularization methods have been optimized for tissue‐/organ‐derived dECM, the methods for cultured cell‐derived dECM have not yet been optimized. Here, two physical (osmotic shocks) and five chemical decellularization methods are compared. The decellularization efficacies were changed according to the decellularization methods used. Among them, only the Triton X‐100 and Tween 20 treatments could not decellularize completely. Additionally, when the efficacies were compared among different types of cells (monolayered cells with/without strong cell adhesion, multilayered cells), the efficacies were decreased for multilayered cells or cells with strong cell adhesion. Retained ECM contents tended to be greater in the dECM prepared by osmotic shocks than in those prepared by chemical methods. The contents impacted cell adhesion, shapes, growth and intracellular signal activation on the dECM. The comparison would be helpful for the optimization of decellularization methods for cultured cells, and it could also provide new insights into developing milder decellularization methods for tissues and organs.
Automatic generation of complementary auxiliary basis sets for explicitly correlated methods
Authors: Semidalas Emmanouil , Martin Jan M. L.
Published: July 2022

Explicitly correlated calculations, aside from the orbital basis set, typically require three auxiliary basis sets: Coulomb‐exchange fitting (JK), resolution of the identity MP2 (RI‐MP2), and complementary auxiliary basis set (CABS). If unavailable for the orbital basis set and chemical elements of interest, the first two can be auto‐generated on the fly using existing algorithms, but not the third. In this paper, we present a quite simple algorithm named autoCABS; a Python implementation under a free software license is offered at Github. For the cc‐pVnZ‐F12 (n = D,T,Q,5), the W4‐08 thermochemical benchmark, and the HFREQ2014 set of harmonic frequencies, we demonstrate that autoCABS‐generated CABS basis sets are comparable in quality to purpose‐optimized OptRI basis sets from the literature, and that the quality difference becomes entirely negligible as n increases.
Reference values for MRI‐derived psoas and paraspinal muscles and macroscopic fat infiltrations in paraspinal muscles in children
Authors: Marunowski Kacper , Świętoń Dominik , Bzyl Włodzimierz , Grzywińska Małgorzata , Bandosz Piotr , Khrichenko Dmitry , Piskunowicz Maciej
Published: July 2022

Background

Sarcopenia, defined as loss of skeletal muscle mass, is a novel term associated with adverse outcomes in children. Magnetic Resonance Imaging (MRI) is a safe and precise technique for measuring tissue compartments and is commonly used in most routine paediatric imaging protocols. Currently, there is a lack of MRI‐derived normative data which can help in determining the level of sarcopenia. This study aimed to introduce reference values of total psoas muscle area (tPMA), total paraspinal muscle area (tPSMA), and total macroscopic fat infiltrations of the PSMA (tMFI).

Methods

In this retrospective study, the local database was searched for abdominal and pelvic region MRI studies of children aged from 1 to 18 years (mean age (standard deviation (SD)) of 9.8 (5.5) years) performed in the years 2010–2021. Children with chronic diseases and a history of surgical interventions were excluded from the analysis. Finally, a total of 465 healthy children (n = 233 girls, n = 232 boys) were enrolled in the study. The values of the tPMA, tPMSA, and tMFI were measured in square centimetres (cm2) at the level of the L4/L5 intervertebral disc as the sum of the left and right regions. Age‐specific and sex‐specific muscle, fat, and body mass index percentile charts were constructed using the LMS method. Inter‐observer agreement and intra‐observer reproducibility were assessed using the Bland–Altman plots.

Results

Both tPMA and tPSMA showed continuous increases in size (in cm2) throughout all age groups. At the age of 18, the median tPMA areas reached 26.37 cm2 in girls and 40.43 cm2 in boys. Corresponding tPSMA values were higher, reaching the level of 40.76 cm2 in girls and 56.66 cm2 in boys. The mean value of tMFI within the paraspinal muscles was 5.0% (SD 3.65%) of their total area in girls and 3.5% (SD 2.25%) in boys with the actual difference between sexes up to 0.96 cm2. Excellent intra‐observer reproducibility and inter‐observer agreement were noted. Actual mean differences for tPMA were at the level of 0.43 and 0.39 cm2, respectively. Mean bias for tPSMA was 0.1 cm2 for inter‐observer and 0.05 cm2 for intra‐observer measurements.

Conclusions

Our findings demonstrate novel and highly reproducible sex‐specific MRI‐derived reference values of tPMS, tPSMA, and tMFI at the level of the L4/L5 intervertebral disc for children from 1 to 18 years old, which may guide a clinician in the assessment of sarcopenia, a prognostic outcome marker in children.
Accelerating investigation of new HIV drugs in pregnancy: advancing the research agenda from theory to action
Authors: Penazzato Martina , Lockman Shahin , Colbers Angela , Renaud Françoise , Calmy Alexandra , Clayden Polly , Vicari Marissa , Mahaka Imelda C. , Zech Jennifer M. , Irvine Cadi , Abrams Elaine J. ,   the participants of the WHO‐IMPAACT Workshop “Approaches to Enhance and Accelerate Study of New Drugs for HIV and Associated Infections in Pregnant Women”
Published: July 2022

Introduction

Historical approaches to clinical development of novel therapeutics for treatment and prevention of HIV have led to unacceptable delays in the generation of data to support optimal antiretroviral drug use in pregnancy. Over the last 5 years, multiple stakeholders have voiced their concerns around the exclusion of pregnant women from drug trials, and some progress has been made to consolidate principles and forge consensus. Building on ongoing efforts, the World Health Organization (WHO) and the International Maternal Paediatric Adolescent AIDS Clinical Trials Network (IMPAACT) convened a technical consultation designed to move the discussion from theory to practice.

Discussion

Accelerating the inclusion of pregnant women in pre‐licensure clinical trials, with a goal to have pharmacokinetics (PK) and preliminary safety data for all new HIV agents in pregnancy available at the time of drug approval, requires: (1) performing non‐clinical developmental and reproductive toxicology studies early in drug development for all new HIV agents; (2) recognizing and acting on the central role of women of childbearing potential affected by HIV through the research being conducted and the dissemination of associated results; (3) enrolling pregnant women in studies to specifically determine pregnancy PK and preliminary safety, as soon as late non‐clinical studies are completed with no negative signals, for all new HIV agents that have demonstrated preliminary evidence of safety and efficacy from phase 2 trials; (4) investigating adverse pregnancy and birth outcomes through dedicated pregnancy safety studies for all new priority HIV agents; and (5) expanding active surveillance of drug safety in pregnancy for rare events, such as birth defects.

Strategic actions to pursue include developing tools and resources to support designing and implementing studies among pregnant and breastfeeding women, identifying and promoting modifications of the regulatory framework that are supportive of systematic ethical investigation of new drugs in pregnancy, coordinating surveillance efforts, mobilizing key stakeholders and promoting transparency and accountability for all involved.

Conclusions

With more than 19 million women living with HIV worldwide, ensuring greater inclusion of pregnant women in research on novel therapeutics is a priority to support drug optimization and effective introduction of innovations for treatment and prevention of HIV.
Surveillance of ARV safety in pregnancy and breastfeeding: towards a new framework
Authors: Renaud Françoise , Mofenson Lynne M. , Bakker Charlotte , Dolk Helen , Leroy Valeriane , Namiba Angelina , Sahin Leyla , Shapiro Roger , Slogrove Amy , Thorne Claire , Vicari Marissa , Low‐Beer Daniel , Doherty Meg
Published: July 2022

Introduction

As new antiretrovirals (ARVs), including long‐acting ARVs for treatment and prevention, are approved and introduced, surveillance during pregnancy must become the safety net for evaluating birth outcomes, especially those that are rare and require large numbers of observations. Historically, drug pharmacovigilance in pregnancy has been limited and fragmented between different data sources, resulting in inadequate data to assess risk. The International Maternal Pediatric Adolescent AIDS Clinical Trials Network and World Health Organization convened a Workshop which reviewed strengths and weaknesses of existing programs and discussed an improved framework to integrate existing safety data sources and promote harmonization and digitalization.

Discussion

This paper highlights that although robust sources of safety data and surveillance programs exist, key challenges remain, including unknown denominators, reporting bias, under‐reporting (e.g. in voluntary registries), few data sources from resource‐limited settings (most are in North America and Europe), incomplete or inaccurate data (e.g. within routine medical records). However, recent experiences (e.g. with safety signals) and current innovations (e.g. electronic record use in resource‐limited settings and defining adverse outcomes) provide momentum and building blocks for a new framework for active surveillance of ARV safety in pregnancy. A public health approach should be taken using data from existing sources, including registries of pregnancy ARV exposure and birth defects; observational surveillance and cohort studies; clinical trials; and real‐world databases. Key facilitators are harmonization and standardization of outcomes, sharing of materials and tools, and data linkages between programs. Other key facilitators include the development of guidance to estimate sample size and duration of surveillance, ensuring strategic geographic diversity, bringing partners together to share information and engaging the community of women living with HIV.

Conclusions

Looking ahead, critical steps to safely introduce new ARVs include (1) adopting harmonized standards for measuring adverse maternal, birth and infant outcomes; (2) establishing surveillance centres of excellence in areas with high HIV prevalence with harmonized data collection and optimized electronic health records linking maternal/infant data; and (3) creating targets and evaluation goals for reporting progress on implementation and quality of surveillance in pregnancy. The platform will be leveraged to ensure that appropriate contributions and strategic actions by relevant stakeholders are implemented.
Avoiding Unnecessary Systematic Biopsy in Clinically Significant Prostate Cancer: Comparison Between MRI‐Based Radiomics Model and PI‐RADS Category
Authors: Cheng Xueqing , Chen Yuntian , Xu Hui , Ye Lei , Tong Shun , Li Haixia , Zhang Tianjing , Tian Song , Qi Jin , Zeng Hao , Yao Jin , Song Bin
Published: July 2022

Background

MRI‐targeted biopsy (MRTB) improves the clinically significant prostate cancer (csPCa) detection rate with fewer biopsy cores in men with suspected PCa. However, whether concurrent systematic biopsy (SB) can be avoided in patients undergoing MRTB remains unclear.

Purpose

To evaluate the potential value of MRI‐based radiomics models in avoiding unnecessary SB in biopsy‐naïve patients.

Study type

Retrospective.

Population

A total of 226 patients (mean age 66.6 ± 9.02 years) with suspicion of PCa (PI‐RADS score ≥ 3) and received combined cognitive MRTB with SB were retrospectively recruited and randomly divided into training (N = 180) and test (N = 46) cohorts at an 8:2 ratio.

Field Strength/Sequence

A 3.0 T, biparametric MRI (bpMRI) including T2‐weighted imaging (T2WI) and apparent diffusion coefficient (ADC) map.

Assessment

The whole prostate gland (PG) and the index lesion (IL) were delineated. Three radiomics models of bpMRIPG, bpMRIIL, and bpMRIPG+IL were constructed, respectively, and the performance of each radiomics model was compared with that of PI‐RADS assessment.

Statistical Tests

The least absolute shrinkage and selection operator (LASSO) regression method was used to select texture features. The area under the curve (AUC) and decision curve analysis were used to estimate the models.

Results

The bpMRIPG+IL radiomics model exhibited good discrimination, calibration, and net benefits, which would reduce the SB biopsy in 71.2% and 71.4% of men with PI‐RADS ≥ 5 lesions in the training and test cohorts, respectively.

Data Conclusion

A bpMRIPG+IL radiomics model may outperform PI‐RADS category in help reducing unnecessary SB in biopsy‐naïve patients.

Evidence Level

3

Technical Efficacy

Stage 6
Generalizability of Deep Learning Segmentation Algorithms for Automated Assessment of Cartilage Morphology and MRI Relaxometry
Authors: Schmidt Andrew M. , Desai Arjun D. , Watkins Lauren E. , Crowder Hollis A. , Black Marianne S. , Mazzoli Valentina , Rubin Elka B. , Lu Quin , MacKay James W. , Boutin Robert D. , Kogan Feliks , Gold Garry E. , Hargreaves Brian A. , Chaudhari Akshay S.
Published: July 2022

Background

Deep learning (DL)‐based automatic segmentation models can expedite manual segmentation yet require resource‐intensive fine‐tuning before deployment on new datasets. The generalizability of DL methods to new datasets without fine‐tuning is not well characterized.

Purpose

Evaluate the generalizability of DL‐based models by deploying pretrained models on independent datasets varying by MR scanner, acquisition parameters, and subject population.

Study Type

Retrospective based on prospectively acquired data.

Population

Overall test dataset: 59 subjects (26 females); Study 1: 5 healthy subjects (zero females), Study 2: 8 healthy subjects (eight females), Study 3: 10 subjects with osteoarthritis (eight females), Study 4: 36 subjects with various knee pathology (10 females).

Field Strength/Sequence

A 3‐T, quantitative double‐echo steady state (qDESS).

Assessment

Four annotators manually segmented knee cartilage. Each reader segmented one of four qDESS datasets in the test dataset. Two DL models, one trained on qDESS data and another on Osteoarthritis Initiative (OAI)‐DESS data, were assessed. Manual and automatic segmentations were compared by quantifying variations in segmentation accuracy, volume, and T2 relaxation times for superficial and deep cartilage.

Statistical Tests

Dice similarity coefficient (DSC) for segmentation accuracy. Lin's concordance correlation coefficient (CCC), Wilcoxon rank‐sum tests, root‐mean‐squared error‐coefficient‐of‐variation to quantify manual vs. automatic T2 and volume variations. Bland–Altman plots for manual vs. automatic T2 agreement. A P value < 0.05 was considered statistically significant.

Results

DSCs for the qDESS‐trained model, 0.79–0.93, were higher than those for the OAI‐DESS‐trained model, 0.59–0.79. T2 and volume CCCs for the qDESS‐trained model, 0.75–0.98 and 0.47–0.95, were higher than respective CCCs for the OAI‐DESS‐trained model, 0.35–0.90 and 0.13–0.84. Bland–Altman 95% limits of agreement for superficial and deep cartilage T2 were lower for the qDESS‐trained model, ±2.4 msec and ±4.0 msec, than the OAI‐DESS‐trained model, ±4.4 msec and ±5.2 msec.

Data Conclusion

The qDESS‐trained model may generalize well to independent qDESS datasets regardless of MR scanner, acquisition parameters, and subject population.

Evidence Level

1

Technical Efficacy

Stage 1
Determination of the relationship between respiration rate and ethylene production by fruit sizes of different tomato types
Authors: Ustun Hayri , Dogan Adem , Peker Bunyamin , Ural Cansu , Cetin Mustafa , Ozyigit Yunus , Erkan Mustafa
Published: July 2022

BACKGROUND

Tomatoes of different types and cultivars are grown in different parts of the world. Accordingly, the phenological, pomological and biochemical characteristics of these types and cultivars may differ from each other, and therefore their ripening behaviours may also differ. The present study aimed to determine the respiration rate and ethylene production of twelve commonly grown cultivars in Turkey at harvest and during the ripening stage. The fruits were harvested at the mature green stage and categorized according to their size as small, medium and large‐fruited cultivars.

RESULTS

At harvest time, the highest respiration rate was determined from ‘Moda’ (small‐fruited) cultivar and the lowest was from ‘Elips’ (medium‐fruited). The highest ethylene production was determined from ‘Sarikiz’ (small‐fruited) and the lowest was from ‘Alberty’ (large‐fruited). All tomato cultivars examined in the study showed climacteric respiration behavior during the ripening, and it was determined that small‐fruited types had a higher respiration rate and ethylene production compared to medium and large‐fruited ones. ‘Sarikiz’ (small‐fruited) had the highest climacteric peak and ‘Gulpembe’ (large‐fruited) had the lowest. Moreover, it was determined that the respiration rate of small‐fruited cultivars were 5.01‐fold higher compared to other cultivars and this type of cultivars produced 4.19‐fold higher ethylene compared to big‐fruited cultivars at harvest. Medium‐fruited tomatoes had 1.90‐fold higher respiration rate and 1.64‐fold ethylene production compared to big‐fruited tomatoes.

CONCLUSION

It was determined that fruit size and respiration rate were related independently of the cultivars, although there was no relationship between fruit size and ethylene production. © 2022 Society of Chemical Industry.
Perceived threat of informal players: Enhancing the operational performance of inbound tour operators through coopetition
Authors: Abdalla Moh'd Juma , Mwesiumo Deodat , Öztüren Ali , Kılıç Hasan
Published: July 2022

This paper explores the effect of the perceived threat of informal tourism actors on the operational performance of formal actors. Based on data collected from 130 inbound tour operators, the paper develops and tests a conceptual model representing the effect of the perceived threat of informal actors. The analysis has revealed a complementary partial mediation effect of the perceived threat of informal actors on operational performance. The perceived threat of informal actors is significantly associated with operating performance, both directly and indirectly, via increased coopetition among tour operators. The findings provide a basis for theoretical and managerial recommendations.
Diagnostic Delay in Human Papillomavirus Negative Oropharyngeal Squamous Cell Carcinoma
Authors: Karp Emily E. , Yin Linda X. , O'Byrne Thomas Jamie , Lu Lauren Y. , Routman David M. , Lester Scott C. , Neben Wittich Michelle A. , Ma Daniel J. , Price Katharine A. , Chintakuntlawar Ashish V. , Tasche Kendall K. , Price Daniel L. , Moore Eric J. , Van Abel Kathryn M.
Published: July 2022

Objective

Failure to recognize symptoms of non‐human papillomavirus‐associated oropharyngeal squamous cell carcinoma (HPV(−)OPSCC) at presentation can delay diagnosis and treatment. We aim to identify patient factors and provider practice patterns that delay presentation and care in HPV(−)OPSCC.

Methods

Retrospective review at a tertiary care center. Patients with HPV(−)OPSCC receiving treatment from 2006 to 2016. Patients were excluded if their date of symptom onset or diagnosis was unknown after thorough review of the electronic medical record or their tissue was not tested for HPV or p16. Clinical data, workup, and care timelines were abstracted. Univariate and multivariable linear regressions were performed to determine associations between patient and provider factors and delays in care.

Results

Of 70 included patients, 52 (74%) were male and mean age was 60.5 (SD = 9.0). Median time to diagnosis was 69 days (IQR = 32–127 days), with a median latency of 30 days (IQR = 12–61 days) from symptom onset to first presentation and 19.5 days (IQR = 4–46 days) from the first presentation to diagnosis. Most patients visited at least 2 providers (n = 52, 74%) before diagnosis. Evaluation by 3 or more providers prior to diagnosis was associated with significant delays in diagnosis of nearly a year (357.7 days, p < 0.001) and being treated or prescribed analgesia prior to diagnosis was significantly associated with delays in diagnosis (p = 0.004) on univariate regression analysis.

Conclusions

Delays in care related to evaluations by multiple providers and misdiagnosis prolonged time to diagnosis in HPV(−)OPSCC. Improved patient and provider education is necessary to expedite the diagnosis of HPV(−)OPSCC.

Level of Evidence

4 Laryngoscope, 133:1394–1401, 2023
A compositional analysis study of body composition and cardiometabolic risk factors
Authors: Janssen Ian , Miller Erin , Dzongowski Erin , Miakisheva Kristina , Ross Robert
Published: July 2022

Objective

This cross‐sectional study used compositional data analysis (CoDA) to do the following: 1) analyze the relative associations between fat and lean tissues with cardiometabolic risk factors; and 2) estimate how these risk factors would change if equivalent mass was displaced from one tissue to another. Differences between CoDA and traditional regression were explored.

Methods

A total of 397 adults with overweight or obesity were studied. Body composition consisted of visceral fat, abdominal subcutaneous fat, peripheral subcutaneous fat, other fat depots, skeletal muscle, and other lean tissues. The outcomes were a continuous metabolic syndrome score (primary outcome) and eight other cardiometabolic risk factors (secondary outcomes). Associations were examined using CoDA and traditional linear regression.

Results

Visceral fat mass, relative to the mass of the remaining tissues, was significantly associated with the metabolic syndrome score and five of eight remaining risk factors (p < 0.05). The relative contribution of the remaining tissues was not consistently associated with the study outcomes. Displacing equivalent mass from visceral fat into the remaining tissues was associated with meaningful decreases in the metabolic syndrome score. Regression estimates for CoDA and traditional regression differed in size and statistical significance.

Conclusions

These CoDA findings reinforce that excess visceral fat contributes to less‐favorable cardiometabolic risk factors.
Hydrophilic shape memory polymer hydrogels with virous pore structures and shape changing performance
Authors: Lv Yang , Chen Xiaohu , Zhang Peicong , Zhou Shiyi , Li Junfeng , Bai Ruqing , Wang Li
Published: July 2022

The preparation of a porous shape memory hydrogel with excellent shape changing performance is a hot research topic at present. In this paper, hydrophilic hydrogels were synthesized using polypropylene glycol (PPG) and polyethylene glycol (PEG) as raw materials and hexamethylene diisocyanate (HDI) as crosslinking agent. The pore structures were developed by gas foaming and salt leaching methods. The results showed that the hydrophilicity of hydrogel and the swelling rate in phosphate buffered saline (PBS) increased with the increase of PEG mass fraction, the shape changing performance of hydrogels varied as well with high shape recovery rate ≥90%. The recovery speed in aqueous environment was faster than in the air. After embedding hydroxyapatite (HA) particles, the materials exhibited appropriate degradable properties and good in vitro mineralization performance. Therefore, the obtained PPG/PEG system hydrogels is expected to become an ideal platform for tissue engineering and other applications in the biomedical field.
Who benefits from an eHealth‐based stress management intervention in advanced prostate cancer? Results from a randomized controlled trial
Authors: Benzo Roberto M. , Moreno Patricia I. , Noriega‐Esquives Blanca , Otto Amy K. , Penedo Frank J.
Published: July 2022

Objective

Conduct a secondary analysis to examine the effects of a tablet‐delivered, group‐based cognitive‐behavioral stress management (CBSM) intervention for reducing symptom burden among men with advanced prostate cancer (APC) and elevated baseline levels of symptom burden.

Methods

A total of 192 men with APC were randomized to either a CBSM or a health promotion condition and followed for one year. Six analytical samples were included in our study, each including participants who reported elevated levels of burden for the corresponding outcome at baseline. Outcomes included five domains of symptom‐related quality of life (urinary incontinence n = 98; urinary irritation n = 61; bowel function n = 43; sexual function n = 177; and hormonal function n = 149) and depression (n = 31). Repeated measures mixed models were used to detect within‐ and between‐group changes in outcomes.

Results

Regardless of condition, participants with elevated symptom burden or mild‐to‐severe depression showed short‐term (6‐month) improvements in urinary irritation, bowel function, hormonal function, and depression scores. Only participants in the CBSM condition showed short‐term (6‐month) improvements in urinary incontinence, and long‐term (12‐month) improvements in urinary irritation, bowel function, hormonal function, and depression scores.

Conclusions

Our findings suggest that targeting a web‐based CBSM intervention to recipients most likely to benefit (elevated levels of symptom burden) can improve several domains of symptom‐related quality of life and depressive symptoms in men with APC.
Machine learning‐guided covariate selection for time‐to‐event models developed from a small sample of real‐world patients receiving bevacizumab treatment
Authors: Karatza Eleni , Papachristos Apostolos , Sivolapenko Gregory B. , Gonzalez Daniel
Published: July 2022

Therapeutic outcomes in patients with metastatic colorectal cancer (mCRC) receiving bevacizumab treatment are highly variable, and a reliable predictive factor is not available. Progression‐free survival (PFS) and overall survival (OS) were recorded from an observational, prospective study after 5 years of follow‐up, including 46 patients with mCRC receiving bevacizumab treatment. Three vascular endothelial growth factor (VEGF)‐A and two intercellular adhesion molecule‐1 genes polymorphisms, age, gender, weight, dosing scheme, and co‐treatments were collected. Given the relatively small number of events (37 [80%] for the PFS and 26 [57%] for the OS), to study the effect of these covariates on PFS and OS, a covariate analysis was performed using statistical and supervised machine learning techniques, including Cox regression, penalized Cox regression techniques (least absolute shrinkage and selection operator [LASSO], ridge regression, and elastic net), survival trees, and survival forest. The predictive performance of each method was evaluated in bootstrapped samples, using prediction error curves and the area under the curve of the receiver operating characteristic. The LASSO penalized Cox‐regression model showed the best overall performance. Nonlinear mixed effects (NLME) models were developed, and a conventional stepwise covariate search was performed. Then, covariates identified as important by the LASSO model were included in the base NLME models developed for PFS and OS, resulting in improved models as compared to those obtained with the stepwise covariate search. It was shown that having gene polymorphisms in VEGFA (rs699947 and rs1570360) and ICAM1 (rs1799969) are associated with a favorable clinical outcome in patients with mCRC receiving bevacizumab treatment.
Determination and enantioselective separation of zilpaterol in human urine after mimicking consumption of contaminated meat using high‐performance liquid chromatography with tandem mass spectrometry techniques
Authors: Euler Luisa , Wagener Felicitas , Thomas Andreas , Thevis Mario
Published: July 2022

Rationale

The synthetic β‐adrenoreceptor agonist zilpaterol is legitimately used as an animal feed supplement in selected countries due to its known effects on lipolysis and protein biosynthesis. These pharmacological characteristics of zilpaterol have contributed to its classification as doping agent in sport by the World Anti‐Doping Agency. However, the use as a feed supplement can lead to residues of the drug in edible tissues and, possibly, also in the urine of consumers.

Methods

To provide urinary elimination profiles of microdosed zilpaterol and to determine whether the ingestion of zilpaterol below or at the acceptable daily intake level of 0.04 μg/kg bodyweight can result in an adverse analytical finding (AAF) in doping controls, healthy volunteers were administered single or multiple oral doses of 0.5 μg or 3 μg zilpaterol to mimic ingestion of contaminated cattle meat. Urine samples were collected and analyzed using a validated high‐performance liquid chromatography‐electrospray ionization‐tandem mass spectrometry (HPLC‐ESI‐MS/MS) method and a newly developed chiral high‐performance liquid chromatography–atmospheric pressure chemical ionization–tandem mass spectrometry (HPLC‐APCI‐MS/MS) method.

Results

Urinary peak concentrations of zilpaterol were observed for all volunteers 1.5–12.5 h after ingestion, and maximum levels >5 ng/mL, which would constitute an AAF in doping controls, were found after the intake of 3 μg of zilpaterol on five consecutive days in one out of five study participants. Noteworthy, the enantiomeric ratio of excreted zilpaterol remained constant over time.

Conclusion

This study provides first insights into the urinary excretion of microdosed zilpaterol. Furthermore, a method was successfully developed and applied for the separation of the zilpaterol enantiomers with mass spectrometric detection.
On the conformal spin dependence of the perturbative QCD vacuum singularity
Authors: Chachamis Grigorios , Vera Agustín Sabio
Published: July 2022

Abstract

We study the four-gluon scattering amplitude in the high energy limit of QCD written in terms of its conformal expansion. We highlight the need to include both even and odd conformal spin contributions in order to map it to an iterative representation in rapidity and transverse momentum space which we have evaluated numerically. By Fourier expanding in a set of three azimuthal angles, we find a new form for the amplitude in terms of 4F3 hypergeometric functions. An alternative formulation is possible when connecting this Fourier expansion with Bessel kernels studied in analytic number theory.
Surgical Management of Amiodarone‐associated Thyrotoxicosis: Too Risky or Too Effective?
Authors: Hamoir Etienne , Meurisse Michel , Defechereux Thierry , Joris Jean , Vivario Janine , Hennen Georges
Published: July 2022

Amiodarone‐associated thyrotoxicosis, often clinically mild and resolutive after amiodarone discontinuation or under medical therapy, is sometimes drug unresponsive and not uncommonly follows a dramatic, even fatal course. Therefore, we considered a surgical solution in 15 severely amiodarone‐associated thyrotoxic patients. Twelve men and three women (mean age 68 years, range 50–84 years) underwent radical thyroidectomy for clinical and biologically proved amiodarone‐associated thyrotoxicosis. In six surgery was the first‐line therapeutic option. In the other nine thyroidectomy seemed unavoidable considering the unresponsiveness to medical therapy and rapid deterioration of the patients’ clinical condition, with life‐threatening cardiac failure in three. In every patient surgery was conducted without immediate or delayed complications. Total thyroidectomy proved uniformly, definitively, and rapidly effective in controlling thyrotoxicosis in all patients, with a spectacular reversal of cardiac failure in the three most critical cases. Surgery was beneficial to our 15 patients and undoubtedly life‐saving in the three most worrying cases. These results suggest that thyroidectomy should be more liberally regarded as an interesting alternative to conventional, but unpredictably effective, medical therapies.
Does tranexamic acid reliably reduce blood loss in proximal femur fracture surgery?
Authors: Fenwick A. , Antonovska I. , Pfann M. , Mayr J. , Wiedl A. , Nuber S. , Förch S. , Mayr E.
Published: July 2022

Purpose

The aim of our study was to investigate the use of tranexamic acid in patients with proximal femoral fractures and compare the total blood loss, transfusion rates, complications, and the application method.

Methods

A retrospective single center cohort study (level I trauma center) with 1479 patients treated operatively for a proximal femoral fracture between January 2016 and June 2020 was performed. 1 g of tranexamic acid was applied (systemic, topic or combined application). Patient data, surgical procedure, complications, and mortality were assessed. Hemoglobin levels, blood loss and transfusion rates for patients with and without tranexamic acid and the application methods were compared.

Results

667 femoral neck fractures, 701 pertrochanteric and 109 subtrochanteric fractures were included. Mean age was 80.8 years. 274 patients received tranexamic acid. At admission average hemoglobin was 12.2 g/l. Hemoglobin drop postoperatively was less after tranexamic acid (9.72 vs. 9.35 g/dl). Transfusion rates were lowered significantly by 17.1% after tranexamic acid. Blood loss was reduced for all patients after tranexamic acid independent of fracture morphology. The combination of 1 g i.v. and 1 g topical-applied tranexamic acid seems to be more effective. Complication rates did not differ.

Conclusion

Tranexamic acid is effective in reducing blood loss and transfusion rates, without increasing the risk of thromboembolic events after proximal femoral fractures. For open reduction and nailing and arthroplasty in fracture setting combined topical and single i.v. application seems most effective and closed reduction with nailing can be treated by single dose i.v. application of 1 g tranexamic acid.
Exploring the concept of Cognitive Digital Twin from model-based systems engineering perspective
Authors: Jinzhi Lu , Zhaorui Yang , Xiaochen Zheng , Jian Wang , Dimitris Kiritsis
Published: July 2022

Digital Twin technology has been widely applied in various industry domains. Modern industrial systems are highly complex consisting of multiple interrelated systems, subsystems and components. During the lifecycle of an industrial system, multiple digital twin models might be created related to different domains and lifecycle phases. The integration of these relevant models is crucial for creating higher-level intelligent systems. The Cognitive Digital Twin (CDT) concept has been proposed to address this challenge by empowering digital twins with augmented semantic capabilities. It aims at identifying the dynamics and interrelationships of virtual models, thus to enhance complexity management capability and to support decision-making during the entire system lifecycle. This paper aims to explore the CDT concept and its core elements following a systems engineering approach. A conceptual architecture is designed according to the ISO 42010 standard to support CDT development; and an application framework enabled by knowledge graph is provided to guide the CDT applications. In addition, an enabling tool-chain is proposed corresponding to the framework to facilitate the implementation of CDT. Finally, a case study is conducted, based on simulation experiments as a proof-of-concept.
Optimization and automation of rapid and selective analysis of fatty acid methyl esters from aqueous samples by headspace SPME arrow extraction followed by GC–MS/MS analysis
Authors: Tintrop Lucie K. , Jochmann Maik A. , Beesley Thomas , Küppers Marco , Brunstermann Ruth , Schmidt Torsten C.
Published: July 2022

The analysis of fatty acid methyl esters (FAMEs) is of high relevance for monitoring and control of various industrial processes and biological systems. In this study, a novel, green analytical approach for the determination of 24 FAMEs from aqueous samples is proposed, which is based on a headspace solid-phase microextraction (SPME) arrow followed by gas chromatography coupled to tandem mass spectrometry (GC–MS/MS). The method was substantially accelerated to a run time of 44 min per sample by thorough optimization and automation of the relevant parameters. The limiting parameters, mostly based on expediting equilibrium attainment, were found to be parameters of extraction: material, pH, time, and temperature, which were optimized to divinylbenzene polydimethylsiloxane (DVB-PDMS), pH 2, 20 min, and 70 °C, respectively. The optimization and automation of the method led to low method detection limits (9–437 ng L−1) and high selectivity. Evaluation of the method on real samples was done by analyzing the aqueous phase of a bioreactor, whereby the matrix effect could be greatly reduced due to dilution and headspace sampling. The rapid, sensitive, selective, and matrix-reduced approach is found to be not only a novel method for water analysis but is promising for further applications, e.g., with solid and gaseous samples containing FAMEs.

Graphical abstract
Influence of N-acetyltransferase 2 (NAT2) genotype/single nucleotide polymorphisms on clearance of isoniazid in tuberculosis patients: a systematic review of population pharmacokinetic models
Authors: Thomas Levin , Raju Arun Prasath , Chaithra  , M Sonal Sekhar , Varma Muralidhar , Saravu Kavitha , Banerjee Mithu , SV Chidananda Sanju , Mallayasamy Surulivelrajan , Rao Mahadev
Published: July 2022

Purpose

Significant pharmacokinetic variabilities have been reported for isoniazid across various populations. We aimed to summarize population pharmacokinetic studies of isoniazid in tuberculosis (TB) patients with a specific focus on the influence of N-acetyltransferase 2 (NAT2) genotype/single-nucleotide polymorphism (SNP) on clearance of isoniazid.

Methods

A systematic search was conducted in PubMed and Embase for articles published in the English language from inception till February 2022 to identify population pharmacokinetic (PopPK) studies of isoniazid. Studies were included if patient population had TB and received isoniazid therapy, non-linear mixed effects modelling, and parametric approach was used for building isoniazid PopPK model and NAT2 genotype/SNP was tested as a covariate for model development.

Results

A total of 12 articles were identified from PubMed, Embase, and hand searching of articles. Isoniazid disposition was described using a two-compartment model with first-order absorption and linear elimination in most of the studies. Significant covariates influencing the pharmacokinetics of isoniazid were NAT2 genotype, body weight, lean body weight, body mass index, fat-free mass, efavirenz, formulation, CD4 cell count, and gender. Majority of studies conducted in adult TB population have reported a twofold or threefold increase in isoniazid clearance for NAT2 rapid acetylators compared to slow acetylators.

Conclusion

The variability in disposition of isoniazid can be majorly attributed to NAT2 genotype. This results in a trimodal clearance pattern with a multi-fold increase in clearance of NAT2 rapid acetylators compared to slow acetylators. Further studies exploring the generalizability/adaptability of developed PopPK models in different clinical settings are required.
Finite-Size Effects in Simulations of Peptide/Lipid Assembly
Authors: Jarin Zack , Agolini Olivia , Pastor Richard W.
Published: July 2022

Molecular dynamics simulations are an attractive tool for understanding lipid/peptide self-assembly but can be plagued by inaccuracies when the system sizes are too small. The general guidance from self-assembly simulations of homogeneous micelles is that the total number of surfactants should be three to five times greater than the equilibrium aggregate number of surfactants per micelle. Herein, the heuristic is tested on the more complicated self-assembly of lipids and amphipathic peptides using the Cooke and Martini 3 coarse-grained models. Cooke model simulations with 50 to 1000 lipids and no peptide are dominated by finite-size effects, with usually one aggregate (micelle or nanodisc) containing most of the lipids forming at each system size. Approximately 200 systems of different peptide/lipid (P/L) ratios and sizes of up to 1000 lipids yield a “finite-size phase diagram” for peptide driven self-assembly, including a coexistence region of micelles and discs. Insights from the Cooke model are applied to the assembly of dimyristoylphosphatidylcholine and the ELK-neutral peptide using the Martini 3 model. Systems of 150, 450, and 900 lipids with P/L = 1/6.25 form mixtures of lipid-rich discs that agree in size with experiment and peptide-rich micelles. Only the 150-lipid system shows finite-size effects, which arise from the long-tailed distribution of aggregate sizes. The general rule of three to five times the equilibrium aggregate size remains a practical heuristic for the Cooke and Martini 3 systems investigated here.

Graphical Abstract
Suture material choice can increase risk of hypersensitivity in hand trauma patients
Authors: Koppa Mayank , House Rosemary , Tobin Vicky , Rozen Warren M. , Hunter-Smith David J. , Goldie Stephen J.
Published: July 2022

Introduction

Hypersensitivity is an unfortunate potential outcome in patients undergoing surgery following traumatic injuries to their hands. In our practice, we noted that certain suture types may increase the risk of the patient developing hypersensitivity.

Methodology

We conducted a retrospective observational study to investigate if certain suture materials increase the risk of hypersensitivity when used to repair surgical wounds in hand trauma. Patients undergoing hand trauma surgery over a period of five consecutive months were included in the study. Ethics committee approval was obtained from Peninsula Health’s research office.

Results

184 patients were included in the study. Hypersensitivity was observed in 30 (16.3%) patients post-operatively. Chromic gut suture was used in 53.3% of the patients who experienced hypersensitivity. Patients who had chromic catgut used in their surgery were 2.82 times more likely to develop hypersensitivity than patients who did not have chromic gut used (p = 0.0015). If a patient had a nerve repaired and chromic gut sutured used, they were 6.50 times more likely to develop hypersensitivity (p < 0.0001).

Conclusion

Surgeons should be aware that this data indicates that suture choice in hand trauma patients can greatly impact the risk of the patient developing hypersensitivity.

Level of evidence: Level IV, risk/prognostic study.