bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk early warning indicators for air traffic controllers' unsafe acts
Authors: Xu Ruihua , Luo Fan , Zhou Fenghua , Chen Gaoming
Published: February 2022

The establishment of an early warning indicator system is the foundation and the key to prevent the unsafe acts of air traffic controllers (ATCers). Therefore, the objective of this study is to determine the early warning indicators for controllers' unsafe acts. Data were encoded through grounded theory and HFACS, and the early warning indicator system was designed. The parameter values were calculated by using the data collected from the expert questionnaire survey. Combining the existing safety performance indicators and expert opinions, the measurement and judgment of indicators were clarified. The results show that the early warning indicator system includes four levels: environment, organization, supervision and ATCers. Among the indicators, the mean values of “degree of job skills mastered,” “intensity of working load,” “lack of safety awareness and responsibility” rank the first three. Based on the findings of this study, the unsafe acts of ATCers can be effectively alerted.
People with Parkinson's disease and housing issues: A scoping review
Authors: Iwarsson Susanne , Andersson Nilla , Slaug Björn , Nilsson Maria H.
Published: February 2022

Background and Aims

There is evidence that housing issues are associated with health outcomes as people age, but little is known in this respect regarding the specific population of people with Parkinson's disease (PD). The objective of this literature review was to identify and analyze the knowledge gap concerning people with PD and housing issues.

Methods

Applying established guidelines for scoping reviews, a systematic literature search was done in relevant databases applying the following inclusion criteria: empirical studies including human participants with PD, addressing housing in the objective, hypothesis or research questions, and published in English in peer‐reviewed journals. Data were analyzed using a framework of domains, factors, and variables influencing housing decisions among older people.

Results

Twelve publications were identified, originating from a few researchers and with very different scopes. While the social dimension was scarcely attended to, the publications addressed all six domains of the analytical framework and 30% of the variables specified therein, but many were only used for descriptive purposes.

Conclusion

This scoping review reveals that there is a substantial knowledge gap regarding people with PD and housing issues. The knowledge gap is most evident in the social dimension, while the studies identified provide more information relating to the health dimension than what is the case in research on housing targeting the general aging population. Because society urgently needs evidence to support the development of housing policies and provide suitable housing for this vulnerable population, more research targeting people with PD and housing issues is warranted.
Current research and future prospects of IVOCT imaging‐based detection of the vascular lumen and vulnerable plaque
Authors: Zhang Ruolin , Fan Yingwei , Qi Wenliu , Wang Ancong , Tang Xiaoying , Gao Tianxin
Published: February 2022

Intravascular optical coherence tomography (IVOCT) is an imaging method that has developed rapidly in recent years and is useful in coronary atherosclerosis diagnosis. It is widely used in the assessment of vulnerable plaque. This review summarizes the main research methods used in recent years for blood vessel lumen boundary detection and segmentation and vulnerable plaque segmentation and classification. This article aims to comprehensively and systematically introduce the research progress on internal tissues of blood vessels based on IVOCT images. The characteristics and advantages of various methods have been summarized to provide theoretical ideas and methods for the reference of relevant researchers and scholars.
Synthesis and biological evaluation of novel 2‐arylquinoline‐3‐fused thiazolo[2,3‐c]1,2,4‐triazole heterocycles as potential antiproliferative and antimicrobial agents
Authors: Dhanavath Ramulu , Dharavath Ravinder , Kothula Devender , Bitla Sampath , Yaku Gugulothu , Birdaraju Saritha , Puchakayala Muralidhar Reddy , Atcha Krishnam Raju
Published: February 2022

A series of novel 2‐arylquinoline‐3‐fused thiazolo[2,3‐c]1,2,4‐triazole heterocycles 9a‐t were efficiently synthesized using simple conventional methods in good yields. The structure of newly synthesized molecules was characterized on the basis of their IR, 1H NMR, 13C NMR and mass spectral data. Among 9a‐t, compounds 9h, 9n, 9b and 9d exhibited highly significant antiproliferative activity against two cancer cell lines C6 (nerve cells) and MCF‐7 (human breast adenocarcinoma cells) when compared with standard reference Doxorubicin. In vitro antimicrobial activities of target compounds 9h, 9b, 9d, 9m and 9n were effectuated on Gram‐positive Staphylococcus aurus (ATCC 25923), Bacillus subtilis (ATCC 6633) and Gram‐negative strains Klebsiella Pneumonia (ATCC 31488) and Escherichia coli (ATCC 25966) strains and found to exhibit promising activity against standard Ciprofloxacin drug. Further, when in vitro antifungal activity was conducted on Aspergillus flavus and Aspergillus niger strains 9h, 9b, 9d and 9n were exhibited potent activity when compared with standard Fluconazole drug moiety.
Synthesis, characterization and crystal structure of some novel partially hydrogenated isoquinolines and their fused heterocyclic systems
Authors: Marae Islam S. , Ibrahim Omaima F. , Abdel‐Hafez Shams H. , Mohamed Shaaban K. , Mague Joel T. , Bakhite Etify A. ‐G.
Published: February 2022

Ketonic hydrolysis of 7‐acetyl‐4‐cyano‐1,6‐dimethyl‐6‐hydroxy‐8‐phenyl‐5,6,7,8‐tetrahydro‐isoquinoline‐3(2H)‐thione (1) via heating with aqueous solution of potassium hydroxide resulted in both deacetylation and dehydration affording new 7,8‐dihydroisoquinoline scaffold (7,8‐DHISQ) 2. Two simple mechanistic approaches are postulated for this synthesis. One of them was supported by converting 7‐acetyl‐4‐cyano‐1,6‐dimethyl‐8‐phenyl‐7,8‐dihydroisoquinoline‐3(2H)‐thione (3) into 7,8‐DHISQ 2 via heating with aqueous solution of potassium hydroxide. Compound 2 was used as a key intetermediate for synthesizing other 7,8‐DHISQ's 4 and 6, as well as 7,8‐dihydrothienoisoquinoline 7. Reaction of compound 3 with 2‐chloroacetamide (8) by refluxing in ethanol containing sodium acetate gave 7‐acetyl‐1‐amino‐5,8‐dimethyl‐6‐phenyl‐6,7‐dihydrothieno[2,3‐c] isoquinoline‐2‐carboxamide (10) which was converted into full aromatized pyrimidothienoisoquinoline 12 on treatment with triethyl orthoformate. Reaction of 3 with both hydrazine hydrate and hydroxylamine hydrochloride afforded tetrahydropyrazolo‐isoquinoline 13 and tetrahydroisoxazoloisoquinoline 14, respectively. Reaction of 14 with N‐(4‐chlorophenyl)‐2‐chloroacetamide (15) produced (N‐phenylcarbamoylmethylthio)tetra‐hydroisoxazoloisoquinoline 16 which was coverted into tetrahydroisoxazolothieno‐isoquinoline 17 upon heating with sodium ethoxide. Also, crystal structures of compounds 4 and 13 were determined via X‐rays diffraction analysis.
Cerebral palsy and sex differences in children: A narrative review of the literature
Authors: Romeo Domenico M. , Venezia Ilaria , Pede Elisa , Brogna Claudia
Published: February 2022

In the last years, new evidence has increased the attention on sex differences in the development of children with cerebral palsy (CP). Males seem to present with a higher risk for severe motor impairment and in the response to chirurgical and rehabilitative interventions. The published data confirmed a higher incidence of CP in males than in females. The aim of this literature review was to evaluate the impact of the sex on the most important areas that characterized CP: motor function, comorbidities (pain, cognitive impairment, communications skills, epilepsy, sleep, and behavior), and the different kind of interventions.
Regional patterns of dry spell durations in Croatia
Authors: Cindrić Kalin Ksenija , Pasarić Zoran
Published: February 2022

The spatiotemporal characteristics of mean and maximum dry spells (DSs) in Croatia were analysed through general climatology and the return values associated with different return periods. An analysis was performed across seven regions with different precipitation regimes comprising data from 131 meteorological stations for 1961–2015. Daily precipitation limits of 1, 5, and 10 mm were used to define dry days, and DSs were defined as consecutive series of dry days. Generalized extreme value (GEV) and generalized Pareto (GP) distributions were applied to the DS annual maxima (AM) and the peak over threshold (POT) series, respectively. The respective distribution parameter methodology and interpretation combined both frequentist and Bayesian approaches. The regional mean DS lengths clearly indicated a dominance of DS durations in easternmost Croatia during the cold season (mainly winter) and in the southern Adriatic during the warm season (mainly summer). Elsewhere, combined climatic influences were reflected, with the shortest DSs found in the highlands. This spatial pattern was more pronounced for DS5 and DS10, whereas differences in DS1 durations were not evident. Spatial DS distribution return values associated with various return periods obtained by the GEV and GP distributions followed the general DS climatology. The visual inspection of an appropriate threshold for GP‐POT modelling, using the GP parameter stability graphs and L‐moment ratio diagrams, indicated that the 75th percentile value was best for all three DS categories. Although the estimates obtained by the two methods could not be directly compared, the GP model generally found longer DS return values than those obtained by the GEV, particularly in the regions with long DS. This study provides a climatological basis for drought parameters and drought risk assessment in Croatia. Moreover, the results are relevant for adjacent regions, complementing and enriching the current DS characteristics knowledge in southeastern Europe.
Immune checkpoint upregulation in periprosthetic joint infection
Authors: Warren Shay I. , Charville Gregory W. , Manasherob Robert , Amanatullah Derek F.
Published: February 2022

Periprosthetic joint infections (PJI) induce an immunosuppressive cytokine profile through an unknown mechanism. Immune checkpoints, like programmed cell death 1 (PD‐1) and its ligand (PD‐L1), initiate innate immunosuppressive pathways essential for self‐tolerance. Several malignancies and chronic infections co‐opt these pathways to derive a survival advantage. This study evaluates PD‐1/PD‐L1 expression in periprosthetic tissue from patients undergoing revision hip or knee arthroplasty for a PJI versus an aseptic failure. PD‐1/PD‐L1 in the global tissue sample and the high‐power microscopic field of maximum expression was analyzed prospectively using immunohistochemistry. Fifteen patients with a PJI (45%) and 16 patients with an aseptic failure (52%) were included. PD‐1 expression was uniformly low. Maximum PD‐L1 expression was upregulated in patients with a PJI (25%, interquartile range [IQR]: 5%–75%) versus an aseptic failure, (8%, IQR: 1%–48%, p = 0.039). In the PJI cohort, maximum PD‐L1 expression was higher among patients who developed a recurrent PJI (68%, IQR: 53%–86% vs. 15%, IQR: 5%–70%, p = 0.039). Patients with global PD‐L1 over 5% trended toward a near 22‐fold increase in the odds of reinfection (odds ratio [OR]: 21.9, 95% confidence interval [CI]: 0.9–523.5, p = 0.057) and patients with maximum PD‐L1 over 20% trended toward a 15‐fold increase in the odds of reinfection (OR: 15.0, 95% CI: 0.6–348.9, p = 0.092). These results support immune checkpoint upregulation as a mechanism of PJI‐induced local immune dysfunction. Future studies should confirm PD‐L1 as a risk factor for reinfection in larger cohorts.
Cloning, expression, and characterization of a novel endo‐type alginate lyase from Microbulbifer sp. BY17
Authors: Yan Fen , Chen Junying , Cai Ting , Zhong Jinfu , Zhang Shaolong
Published: February 2022

BACKGROUND

Alginate oligosaccharides (AOS), with various physiological effects, have been widely used in the food, agricultural, and pharmaceutical industries. The biological enzymatic method of preparing AOS, using alginate lyase, has more advantages compared with physical and chemical methods. Cloning and heterologously expressing alginate lyase are therefore very important.

RESULTS

A novel alginate lyase, BY17PV7, from Microbulbifer sp. BY17, isolated from Gracilaria, was cloned and expressed in Escherichia coli BL21(DE3). BY17PV7 was about 27 KDa. BY17PV7 showed the greatest activity (150.42 3.32 U/mg) at 43 °C and pH 8.9. It could be activated by Ca2+, Mn2+, Co2+, Fe3+, Na+, and inhibited by Mg2+, Zn2+, Ba2+, Cu2+, sodium dodecyl sulfate (SDS), ethylene diamine tetraacetic acid (EDTA). BY17PV7 had a wide range of substrate specificity and good degradation effects for poly β‐D‐mannuronate (polyM) and poly α‐L‐guluronate (polyG), demonstrating that it is a bifunctional alginate lyase. The kinetic parameters showed that BY17PV7 had a greater affinity for polyG. BY17PV7 released AOS with a degree of polymerization (DP) of 3–4 in an endolytic manner from sodium alginate. Alginate oligosaccharides showed strong antioxidant ability of reducing Fe3+ and scavenging radicals such as hydroxyl, 2,2‐azion‐bia (3‐ethylbenzo‐thiazoline‐6‐sulfonic acid diammonium salt) (ABTS) and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH).

CONCLUSION

A novel bifunctional alginate lyase, BY17PV7, was expressed and characterized in Escherichia coli BL21(DE3). The results were helpful for the analysis of the molecular mechanisms of degrading patterns in the polysaccharide lyase (PL) family. © 2022 Society of Chemical Industry.
Analysis of tamoxifen and its main metabolites in plasma samples of breast cancer survivor female athletes: Multivariate and chemometric optimization
Authors: Sadeghcheh Tahereh , Saber Tehrani Mohammad , Faraji Hakim , Aberoomand Azar Parviz , Helalizadeh Masoumeh
Published: February 2022

A sensitive method based on liquid chromatography combined with a diode array detector was developed and validated to simultaneously determine tamoxifen, and its active metabolites N‐desmethyltamoxifen, 4‐hydroxytamoxifen, and endoxifen in human plasma samples. The green and sustainable vortex‐assisted dispersive liquid‐phase microextraction technique based on the natural hydrophobic deep eutectic solvent was used for the extraction and preconcentration of the analytes. Chemometrics and multivariate analysis were used to optimize the independent variables including the type and volume of deep eutectic solvent, extraction time, and ionic strength. Under optimal conditions, calibration curves were linear in a suitable range with the lower limits of quantification (0.8–10.0 μg/L), which covered the relevant concentrations of the analytes in plasma samples for a clinical study. Intra‐ and interday precision evaluated at three concentrations for the analytes were lower than 8.2 and 12.1%, respectively. Accuracy was in the range of 94.9–104.7%. The applicability of the developed method on human plasma samples illustrated the range 45.1–72.8, 98.4–128.3, 0.9–1.2, and 2.7–6.1 μg/L for tamoxifen, N‐desmethyltamoxifen, 4‐hydroxytamoxifen, and endoxifen, respectively. The validated method can be effective for the pharmacokinetics, pharmacodynamics, and therapeutic drug monitoring studies of tamoxifen and its main metabolites in biological fluids.
Estimating posttraumatic stress disorder severity in the presence of differential item functioning across populations, comorbidities, and interview measures: Introduction to Project Harmony
Authors: Morgan‐López Antonio A. , Hien Denise A. , Saraiya Tanya C. , Saavedra Lissette M. , Norman Sonya B. , Killeen Therese K. , Simpson Tracy L. , Fitzpatrick Skye , Mills Katherine L. , Ruglass Lesia M. , Back Sudie E. , López‐Castro Teresa ,   the Consortium on Addiction, Stress and Trauma (CAST)
Published: February 2022

Multiple factor analytic and item response theory studies have shown that items/symptoms vary in their relative clinical weights in structured interview measures for posttraumatic stress disorder (PTSD). Despite these findings, the use of total scores, which treat symptoms as though they are equally weighted, predominates in practice, with the consequence of undermining the precision of clinical decision‐making. We conducted an integrative data analysis (IDA) study to harmonize PTSD structured interview data (i.e., recoding of items to a common symptom metric) from 25 studies (total N = 2,568). We aimed to identify (a) measurement noninvariance/differential item functioning (MNI/DIF) across multiple populations, psychiatric comorbidities, and interview measures simultaneously and (b) differences in inferences regarding underlying PTSD severity between scale scores estimated using moderated nonlinear factor analysis (MNLFA) and a total score analog model (TSA). Several predictors of MNI/DIF impacted effect size differences in underlying severity across scale scoring methods. Notably, we observed MNI/DIF substantial enough to bias inferences on underlying PTSD severity for two groups: African Americans and incarcerated women. The findings highlight two issues raised elsewhere in the PTSD psychometrics literature: (a) bias in characterizing underlying PTSD severity and individual‐level treatment outcomes when the psychometric model underlying total scores fails to fit the data and (b) higher latent severity scores, on average, when using DSM‐5 (net of MNI/DIF) criteria, by which multiple factors (e.g., Criterion A discordance across DSM editions, changes to the number/type of symptom clusters, changes to the symptoms themselves) may have impacted severity scoring for some patients.
Extensive hearing loss induced by low‐frequency noise exposure
Authors: Liu Junping , Antisdel Jastin , Liu Changming , Chen Miaoan , Dong Pin , Fahlman Richard , Ma Furong , Yu Yongqiang
Published: February 2022

Background

With little attention given to low‐frequency traffic noise and our understanding that cochlear function may be highly susceptible to low‐frequency noise, there is an urgent need to determine traffic noise‐induced hearing loss (NIHL), not only the hearing loss at low frequency but also the possible high‐frequency hearing loss.

Methods

The current study aims to investigate the potential for extensive hearing loss induced by exposure to 0.063 kHz octave band noise (OBN), which is an important component of low‐frequency traffic noise. The threshold of auditory brainstem response (ABR) was used to evaluate hearing function before and after noise exposure. Chinchillas were randomly assigned into seven different groups. Group 63‐3 h/6 h, Group 2 k‐3 h/6 h, and group 4 k‐3 h/6 h were exposed for either 3 or 6 h to 0.063, 2, and 4 kHz OBN at 90 dB SPL, respectively. The control group was not exposed to noise.

Results

Significant ABR threshold‐shifts (TS) were observed at 0.88, 2, 4, and 5.7 kHz in Group 63‐6 h, and at 2.8 and 4 kHz in Group 2 k‐6 h, and at 5.7 kHz in Group 4 k‐6 h. ABR‐TS were consistent with outer hair cell (OHC) losses, exposure to 0.063 kHz OBN at 90 dB SPL for 6 h induced large‐scale losses of OHC both in low‐ and high‐frequency region.

Conclusions

Exposure to 0.063 kHz low‐frequency OBN at 90 dB SPL for 6 h leads to significant hearing loss over an extensive range from low to high frequencies.
Glomerular filtration rate early after liver transplantation independently predicts atherosclerotic events
Authors: Hassouneh Ramzi , Patel Samarth , Shen Steve , Bui Anh , Syed Taseen , Flynn Sean , Patel Vaishali , Muthiah Mark D. , Sharma Amit , Bhati Chandra , Siddiqui Mohammad Shadab
Published: February 2022

Cardiovascular disease (CVD) is an important cause of mortality among liver transplantation (LT) recipients; however, the data on CVD risk stratification following LT are limited. Thus, the primary aim of this study was to evaluate the association between decline in renal function early after LT and atherosclerotic events. This retrospective study included all patients receiving LT between 2007 and 2019. Early renal function was quantified as estimated glomerular filtration rate (GFR) 6 months after LT. The primary endpoint for the study was a composite atherosclerotic cardiovascular event of three‐point major adverse cardiovascular events (MACEs), which includes nonfatal myocardial infarction (MI), nonfatal stroke, or death from CVD. A total of 553 LT recipients met entry criteria. After a median follow‐up of 74 months (interquartile range 46–111), 94 (17%) LT recipients died and CVD‐associated death occurred in 20 patients. MACE‐3 occurred in 66 (12%) patients, with nonfatal MI being the most common event (n = 30). A strong inverse relationship between early GFR and MACE‐3 was noted in unadjusted analysis with hazard ratio (HR) 0.96 (95% confidence interval [CI] 0.95–0.98; p = 0.0001) and remained significant even after accounting for age, sex, coronary artery disease, diabetes mellitus, hypertension, calcineurin inhibitor use, and Framingham Risk Score (FRS; HR 0.96, 95% CI 0.95–0.97; p = 0.0001 per unit increase in GFR). Furthermore, an independent interaction between GFR, FRS, and likelihood of developing an MACE‐3 was noted. GFR 6 months following LT is a strong predictor of developing atherosclerotic events. This relationship is independent of traditional CVD risk stratification models (e.g. FRS) and thus has the potential to be incorporated into CVD risk assessment after LT but requires further validation.
The Effects of Proline Isomerization on the Solvation Behavior of Elastin‐Like Polypeptides in Water–Ethanol Mixtures
Authors: Zhao Yani , Kremer Kurt
Published: February 2022

Elastin‐like polypeptides (ELPs) are well‐known proline‐rich stimulus‐responsive polymers. They have broad applications ranging from drug delivery to green chemistry. Recently, the authors have shown that the cis/trans proline isomerization can be used to regulate their conformational behavior while keeping the lower critical solution temperature (LCST) unchanged in pure water. In aqueous ethanol mixtures, ELPs typically exhibit an expanded–collapsed–expanded transition known as the co‐non‐solvency phenomenon. Since it is unclear how proline isomerization affects the solvation behavior of ELPs in aqueous ethanol mixtures, an all‐atom insight on single ELPs has been provided to address this question. It is found that if all proline residues are in the cis state, the peptides only experience a collapsed–expanded transition as ethanol concentration increases, i.e., the initial collapse vanishes because cis isomers prefer the compact structures in pure water. The data from the authors also suggest that proline isomerization does not change the shift in solvation free energy of an ELP with given sequence, but it varies the affinity of the peptide to both the solvent and cosolvent molecules.
Non‐cooperative and cooperative environmental corporate social responsibility with emission taxes
Authors: Xu Lili , Lee Sang‐Ho
Published: February 2022

This study examines emission taxes and environmental corporate social responsibility (ECSR) under cooperative and non‐cooperative regimes, respectively, and compares Cournot and Bertrand competitions. We show that (i) there exists substitutability between emission taxes and ECSR, while the cooperative case always yields lower emission taxes and higher ECSR; (ii) environmental damage and social welfare are independent of types of ECSR under Cournot, but both are higher in the cooperative ECSR under Bertrand; and (iii) the cooperative ECSR cannot achieve socially desirable outcomes, whereas the non‐cooperative ECSR is beneficial to society under low marginal damage.
The digital economy, enterprise digital transformation, and enterprise innovation
Authors: Li Rui , Rao Jing , Wan Liangyong
Published: February 2022

Drawing on the resource dependency view, we examine the impact of the regional digital economy on enterprise innovation. Using data on Chinese A‐share listed manufacturing firms between 2011 and 2019, we find that digital economy development is positively associated with enterprise innovation. In addition, the digital economy positively enhances enterprise digital transformation, and enterprise digital transformation has a significant positive effect on enterprise innovation. Thus, enterprise digital transformation partially mediates the relationship between the digital economy and enterprise innovation. Furthermore, enterprise efficiency significantly positively moderates the direct and indirect effects of the digital economy on enterprise innovation.
The Neuroinflammatory Acute Phase Response in Parkinsonian‐Related Disorders
Authors: Ayton Scott , Hall Sara , Janelidze Shorena , Kalinowski Pawel , Palmqvist Sebastian , Belaidi Abdel A. , Roberts Blaine , Roberts Anne , Stomrud Erik , Bush Ashley I. , Hansson Oskar
Published: February 2022

Background

Neuroinflammation is implicated in the pathophysiology of Parkinson's disease (PD) and related conditions, yet prior clinical biomarker data report mixed findings.

Objectives

The aim was to measure a panel of neuroinflammatory acute phase response (APR) proteins in the cerebrospinal fluid (CSF) of participants with PD and related disorders.

Methods

Eleven APR proteins were measured in the CSF of 867 participants from the BioFINDER cohort who were healthy (612) or had a diagnosis of PD (155), multiple system atrophy (MSA) (26), progressive supranuclear palsy (PSP) (22), dementia with Lewy bodies (DLB) (23), or Parkinson's disease with dementia (PDD) (29).

Results

CSF APR proteins were mostly unchanged in PD, with only haptoglobin and α1‐antitrypsin significantly elevated compared to controls. These proteins were variably increased in the other disorders. Certain protein components yielded unique signatures according to diagnosis: ferritin and transthyretin were selectively elevated in MSA and discriminated these patients from all others. Haptoglobin was selectively increased in PSP, discriminating this disease from MSA when used in combination with ferritin and transthyretin. This panel of proteins did not correlate well with severity of motor impairment in any disease category, but several (particularly ceruloplasmin and ferritin) were associated with memory performance (Mini‐Mental State Examination) in patients with DLB and PDD.

Conclusions

These findings provide new insights into inflammatory changes in PD and related disorders while also introducing biomarkers of potential clinical diagnostic utility. © 2022 International Parkinson and Movement Disorder Society
Experiences of children and adolescents living with achondroplasia and their caregivers
Authors: Shediac Renée , Moshkovich Olga , Gerould Heather , Ballinger Rachel , Williams Agnes , Bellenger M. Alex , Quinn Jennifer , Hoover‐Fong Julie , Mohnike Klaus , Savarirayan Ravi , Kelly Dominique
Published: February 2022

Background

Achondroplasia, caused by a pathogenic variant in the fibroblast growth factor receptor 3 gene (FGFR3), leads to significant multisystem complications across the lifespan that may affect the health‐related quality of life (HRQoL) of individuals and families living with the condition.

Methods

The objective of this qualitative study was to describe the HRQoL of children and adolescents with achondroplasia and their caregivers. Thirty‐four caregivers and 12 adolescents from the United States and Spain participated in one of eight focus groups or completed an individual interview, which was audio‐recorded and transcribed. Thematic analysis of qualitative data was performed to identify commonly occurring themes pertaining to HRQoL.

Results

Caregivers and adolescents described challenges with physical functioning and medical complications due to achondroplasia. Key challenges included difficulties performing activities of daily living, issues of accessibility, bullying, or unwanted attention in public, and negative effects on self‐esteem. Caregivers were concerned about accessing appropriate medical care for their child, and also reported experiencing financial, relational, and emotional challenges in their families. Achondroplasia also affected individuals and their families in positive ways, including increasing empathy, receiving positive attention, and feeling supported by the achondroplasia community.

Conclusions

These findings underscore the importance of regular assessments of HRQoL and the provision of psychosocial support to affected children and families.
ChREBP‐driven DNL and PNPLA3 Expression Induced by Liquid Fructose are Essential in the Production of Fatty Liver and Hypertriglyceridemia in a High‐Fat Diet‐Fed Rat Model
Authors: Velázquez Ana Magdalena , Bentanachs Roger , Sala‐Vila Aleix , Lázaro Iolanda , Rodríguez‐Morató Jose , Sánchez Rosa M. , Alegret Marta , Roglans Núria , Laguna Juan Carlos
Published: February 2022

Scope

The aim of this study is to delineate the contribution of dietary saturated fatty acids (FA) versus liquid fructose to fatty liver and hypertriglyceridemia.

Methods and Results

Three groups of female rats are maintained for 3 months in standard chow (CT); High‐fat diet (46.9% of fat‐derived calories, rich in palmitic and stearic FA, HFD); and HFD with 10% w/v fructose in drinking water (HFHFr). Zoometric parameters, plasma biochemistry, and liver Oil‐Red O (ORO) staining, lipidomics, and expression of proteins involved in FA metabolism are analyzed. Both diets increase ingested calories without modifying body weight. Only the HFHFr diet increases liver triglycerides (x11.0), with hypertriglyceridemia (x1.7) and reduces FA β‐oxidation (x0.7), and increases liver FA markers of DNL (de novo lipogenesis). Whereas HFD livers show a high content of ceramides, HFHFr samples show unchanged ceramides, and an increase in diacylglycerols. Only the HFHFr diet leads to a marked increase in the expression of enzymes involved in DNL and triglyceride metabolism, such as carbohydrate response element binding protein β (ChREBPβ, x3.2), a transcription factor that regulates DNL, and patatin‐like phospholipase domain‐containing 3 (PNPLA3, x2.6), a lipase that mobilizes stored triglycerides for VLDL secretion.

Conclusion

The addition of liquid‐fructose to dietary FA is determinant in liver steatosis and hypertriglyceridemia production, through increased DNL and PNPLA3 expression, and reduced FA catabolism.
An initial systematic study of the linear energy transfer distributions of a proton beam under a transverse magnetic field
Authors: Fujii Yusuke , Ueda Hideaki , Umegaki Kikuo , Matsuura Taeko
Published: February 2022

Purpose

To evaluate the biological effectiveness of magnetic resonance (MR)‐guided proton beam therapy, comprehensively characterizing the dose and dose‐averaged linear energy transfer (LETd) distributions under a magnetic field is necessary. Although detailed analysis has characterized curved beam paths and distorted dose distributions, the impact of a magnetic field on LETd should also be explored to determine the proton relative biological effectiveness (RBE). Hence, this initial study aims to present a basic analysis of LETd distributions in the presence of a magnetic field using Monte Carlo simulation (MCS).

Methods

Geant4 MCS (version 10.1.p01) was performed to calculate the LETd distribution of proton beams. The incident beam energies were set to 70.2, 140.8, and 220 MeV, and both zero‐ and finite‐emittance pencil beams as well as scanned field were simulated. A transverse magnetic field of 0–3 T was applied within a water phantom placed at the isocenter, and the three‐dimensional dose and LETd distributions in the phantom were calculated. Then, the depth profiles of LETd along the curved trajectory and the lateral LETd profile at the Bragg peak (BP) depth were analyzed under changing energies and magnetic fields. In addition, for zero‐ and finite‐emittance beams, the correlation of the lateral asymmetries between the dose and LETd distributions were analyzed. Finally, spread‐out Bragg peak (SOBP) fields were simulated to assess the depth‐dependent asymmetry of the LETd distributions.

Results

A transverse magnetic field distorted the lateral LETd distribution of a pencil beam at close to the BP, and the magnitude of the distortion at the BP increased for higher energy beams and larger magnetic fields. For a zero‐emittance beam, the differences in LETd between the left and right D20 positions were relatively large; the difference in LETd was 1.5 and 2.3 keV/μm at 140.8 and 220 MeV, respectively, at a magnetic field of 1.5 T. These asymmetries were pronounced at positions where the dose asymmetries were large. The size of the asymmetry was less substantial for a finite‐emittance beam and even less for a scanned field. However, a 1.5‐keV/μm difference still remained between the left and right D20 positions of a scanned field penumbra for a 220 MeV beam under the same magnetic field. For the SOBP field, it was found that the distal region of SOBP had the highest LETd distortions, followed by the central and proximal regions for the middle‐sized SOBP (5 × 5 × 5 cm3), whereas the degree of LETd distortion did not vary much with depth for the 10 × 10 × 10‐cm3 SOBP field.

Conclusion

Our results indicate that not only the dose but also LETd distortions should be considered to accurately evaluate the biological effectiveness of MR‐guided proton beam therapy.
Mechanism of wetting–induced deformation and failure of unsaturated soils
Authors: Komolvilas Veerayut , Kikumoto Mamoru , Kyokawa Hiroyuki
Published: February 2022

The mechanisms of hydraulic collapse (wetting‐induced deformation) are studied through a series of simulations using a model for unsaturated soils. The model is a critical state soil model extended for unsaturated soils using Bishop's effective stress tensor, the state boundary surface (SBS) moving with the change in the degree of saturation, and a rational soil‐water characteristic curve that takes account of density and hydraulic hysteresis. Comparisons with published experimental data validate the proposed model. The simulation results show that the model adequately captures the hydraulic collapse behavior under both isotropic and anisotropic stress conditions. The effects of density, mean net stress, and deviatoric stress on the hydraulic collapse behavior are further investigated through a parametric calculation, and the mechanics of the wetting–induced instability are discussed. The effects of suction history, namely repeated wetting and drying cycles, on the deformation and failure, are also presented. The proposed model provides a validated method for modeling hydromechanical collapse in unsaturated soil and provides a better understanding of the mechanisms involved.
Vertical dynamic impedance of end‐bearing pile groups embedded in homogeneous unsaturated soils
Authors: Ma Wenjie , Shan Yao , Xiang Ke , Wang Binglong , Zhou Shunhua
Published: February 2022

Although soil is typically an unsaturated (three‐phase) medium, previous studies on the dynamic impedance of pile groups primarily considered the piles embedded in either the single‐phase or fully saturated (two‐phase) soils. In this work, the dynamic impedance of end‐bearing pile groups embedded in homogeneous unsaturated soil subject to a vertical time‐harmonic load is analytically obtained. The soil is modeled as a three‐dimensional axisymmetric continuum, and both the radial and vertical displacements as well as the influence of the saturation degree on the soil's dynamic shear modulus are considered. The governing equations of vibrating unsaturated soil are uncoupled by virtue of the potential function and operator decomposition methods. The attenuation function of soil displacement, surrounding soil resistance factor, and vertical dynamic impedance of a single pile are derived from the pile−soil compatibility conditions. Pile‐to‐pile dynamic interaction factors are then derived and used, along with the superposition principle, to find the vertical dynamic impedance of end‐bearing pile groups in the frequency domain. The proposed analytical solution is verified by comparison with two benchmark solutions. Finally, the influence of various parameters on the dynamic response of end‐bearing pile groups is determined.
Drug interactions in hospital prescriptions in Denmark: Prevalence and associations with adverse outcomes
Authors: Leal Rodríguez Cristina , Kaas‐Hansen Benjamin Skov , Eriksson Robert , Biel Jorge Hernansanz , Belling Kirstine G. , Andersen Stig Ejdrup , Brunak Søren
Published: February 2022

Purpose

While the beneficial effects of medications are numerous, drug–drug interactions may lead to adverse drug reactions that are preventable causes of morbidity and mortality. Our goal was to quantify the prevalence of potential drug–drug interactions in drug prescriptions at Danish hospitals, estimate the risk of adverse outcomes associated with discouraged drug combinations, and highlight the patient types (defined by the primary diagnosis of the admission) that appear to be more affected.

Methods

This cross‐sectional (descriptive part) and cohort study (adverse outcomes part) used hospital electronic health records from two Danish regions (~2.5 million people) from January 2008 through June 2016. We included all inpatients receiving two or more medications during their admission and considered concomitant prescriptions of potentially interacting drugs as per the Danish Drug Interaction Database. We measured the prevalence of potential drug–drug interactions in general and discouraged drug pairs in particular during admissions and associations with adverse outcomes: post‐discharge all‐cause mortality rate, readmission rate and length‐of‐stay.

Results

Among 2 886 227 hospital admissions (945 475 patients; median age 62 years [IQR: 41–74]; 54% female; median number of drugs 7 [IQR: 4–11]), patients in 1 836 170 admissions were exposed to at least one potential drug–drug interaction (659 525 patients; median age 65 years [IQR: 49–77]; 54% female; median number of drugs 9 [IQR: 6–13]) and in 27 605 admissions to a discouraged drug pair (18 192 patients; median age 68 years [IQR: 58–77]; female 46%; median number of drugs 16 [IQR: 11–22]). Meropenem‐valproic acid (HR: 1.5, 95% CI: 1.1–1.9), domperidone‐fluconazole (HR: 2.5, 95% CI: 2.1–3.1), imipramine‐terbinafine (HR: 3.8, 95% CI: 1.2–12), agomelatine‐ciprofloxacin (HR: 2.6, 95% CI: 1.3–5.5), clarithromycin‐quetiapine (HR: 1.7, 95% CI: 1.1–2.7) and piroxicam‐warfarin (HR: 3.4, 95% CI: 1–11.4) were associated with elevated mortality. Confidence interval bounds of pairs associated with readmission were close to 1; length‐of‐stay results were inconclusive.

Conclusions

Well‐described potential drug–drug interactions are still missed and alerts at point of prescription may reduce the risk of harming patients; prescribing clinicians should be alert when using strong inhibitor/inducer drugs (i.e. clarithromycin, valproic acid, terbinafine) and prevalent anticoagulants (i.e. warfarin and non‐steroidal anti‐inflammatory drugs ‐ NSAIDs) due to their great potential for dangerous interactions. The most prominent CYP isoenzyme involved in mortality and readmission rates was 3A4.
Neuromodulation approaches for borderline personality disorder
Authors: Yahya Ahmed Saeed , Khawaja Shakil , Williams Paul Simon , Naguib Meena
Published: February 2022

Borderline personality disorder (BPD) is a complex and serious mental disorder that has a high suicide rate. There is emerging evidence for the use of nonconvulsive neurostimulation therapies, including transcranial magnetic stimulation (TMS), repetitive TMS (rTMS), and transcranial direct current stimulation (tDCS) in controlling some of the characteristic symptoms. Here the authors summarise the current evidence for the efficacy and tolerability of TMS, rTMS and tDCS in managing symptoms of BPD.
Biology and biometric characteristics of Spodoptera frugiperda (Lepidoptera: Noctuidae) reared on different host plants with regard to diet
Authors: Gopalakrishnan Raman , Kalia Vinay Kumari
Published: February 2022

BACKGROUND

The fall armyworm (FAW) Spodoptera frugiperda (J. E. Smith), native to the Americas, is a new invasive pest that was reported in India for the first time in May 2018. Being polyphagous, FAW can infest several different hosts and increase its population all year round. In this context, the present study was conducted under laboratory conditions to evaluate the biological parameters of FAW on four different hosts, Zea mays (maize), Gossypium hirsutum (cotton), Ricinus communis (castor) and Brassica oleracea var. botrytis (cauliflower), and a semi‐synthetic diet.

RESULTS

The shortest life cycle of 32.8 ± 0.52 days in males and 34.1 ± 0.43 days in females was observed on maize. Semi‐synthetic diet was superior in terms of higher mean fecundity (1324.6 ± 61.21 eggs), larval weight (503 ± 0.02 mg), pupal weight (263 ± 0.01 mg) and adult female weight (128 ± 0.0 mg) compared with natural hosts. Cotton was the least preferred host with a longer life cycle of 49.5 ± 0.50 days. Head capsule width and length were measured and the growth rate was validated using Dyar's rule. The mean width and length of the head capsule of first‐instar larvae of FAW on different hosts was 0.35 ± 0.00 mm. The maximum width (2.76 ± 0.03 mm) and length (2.31 ± 0.03 mm) were observed in sixth‐instar larvae grown on diet.

CONCLUSION

The results of this study will be instrumental in understanding and formulating management strategies for FAW.
Consideration of Underlying Immunodeficiency in Refractory or Recalcitrant Warts: A Review of the Literature
Authors: Zampella J. , Cohen B.
Published: February 2022

Although the exact mechanisms have yet to be elucidated, it is clear that cellular immunity plays a role in clearance of human papillomavirus (HPV) infections as it relates to the development of warts. Patients with extensive, recalcitrant, or treatment-refractory warts may have an underlying immune system impairment at the root of HPV susceptibility. Early recognition of genetic disorders associated with immunologic defects that allow for recalcitrant HPV infection may expedite appropriate treatment for patients. Early recognition is often pivotal in preventing subsequent morbidity and/or mortality that may arise from inborn errors of immunity, such as WHIM (Warts, Hypogammaglobulinemia, Infections, Myelokathexis) syndrome. Among these, cervical cancer is one of the most common malignancies associated with HPV, can be fatal if not treated early, and is seen more frequently in patients with underlying immune deficiencies. A review of diseases with susceptibility to HPV provides clues to understanding the pathophysiology of warts. We also present diagnostic guidance to facilitate the recognition of inborn errors of immunity in patients with extensive and/or recalcitrant HPV infections.
Artificial intelligence and the changing sources of competitive advantage
Authors: Krakowski Sebastian , Luger Johannes , Raisch Sebastian
Published: February 2022

Research Summary

We apply a resource‐based view to investigate how the adoption of Artificial Intelligence (AI) affects competitive capabilities and performance. Following prior work on using chess as a controlled setting for studying competitive interactions, we compare the same players’ capabilities and performance across conventional, centaur, and engine chess tournaments. Our analysis shows that AI adoption triggers interrelated substitution and complementation dynamics, which make humans’ traditional competitive capabilities obsolete, while creating new sources of persistent heterogeneity when humans interact with chess engines. These novel human‐machine capabilities are unrelated, or even negatively related, to traditional capabilities. We contribute an integrated view of substitution and complementation, which identifies AI as the driver of these dynamics and explains how they jointly shift the sources of competitive advantage.

Managerial Summary

AI‐based technologies increasingly substitute and complement humans in managerial tasks such as decision making. We investigate how such change affects the sources of competitive advantage. AI‐based engines’ adoption in chess allows us to investigate competitive capabilities and performance in human, AI, and hybrid settings. We find that neither humans nor AI in isolation explain performance differences in the AI and hybrid settings. Instead, a new decision‐making resource emerges at the human‐AI intersection, which drives performance but is unrelated or even negatively related to humans’ original capability. Our results document how AI adoption changes the sources of competitive advantage and, in turn, requires managers to develop new capabilities to stay relevant in an AI‐based competitive landscape.
Molecular Doping Increases the Semitransparent Photovoltaic Performance of Dilute Bulk Heterojunction Film with Discontinuous Polymer Donor Networks
Authors: Tang Yabing , Zheng Hong , Zhou Xiaobo , Tang Zheng , Ma Wei , Yan Han
Published: February 2022

The semitransparent and colorful properties of organic solar cells (OSCs) attract intensive academic interests due to their potential application in building integrated photovoltaics, wearable electronics, and so forth. The most straightforward and effective method to tune these optical properties is varying the componential ratio in the blend film. However, the increase in device transmittance inevitably sacrifices the photovoltaic performance because of severe carrier recombination that originates from discontinuous charge‐transport networks in the blend film. Herein, a strategy is proposed via the molecular‐doping strategy to overcome these shortcomings. It is discovered that p‐doping is able to release the trapped holes in segregated polymer domains leading to short‐circuit current enhancement, while n‐doping is more effective to fill the bandgap states producing a higher fill factor. More importantly, either type of doping improves the photovoltaic performance in the semitransparent photovoltaic devices. These discoveries provide a new pathway to breaking the compromise between the photovoltaic performance and optical transmittance in semitransparent OSCs, and hold promise for their future commercialization.