bluuebunny/crossref_metadata_2025 huggingface dataset:
Perception of genetic testing among patients with inherited retinal disease: Benefits and challenges in a Japanese population
Authors: Inaba Akira , Yoshida Akiko , Maeda Akiko , Kawai Kanako , Kosugi Shinji , Takahashi Masayo
Published: February 2022

Inherited retinal disease (IRD) is clinically and genetically heterogeneous. Awareness of the importance of genetic testing for IRD in the clinical setting is increasing with the recent development of new therapeutic strategies, such as gene therapy. Here, the perception of genetic testing, including its benefits and potential challenges, among patients with IRD was investigated to establish strategies for IRD genetic testing and counseling practices that can meet the requirements of the patients in Japan. An anonymous self‐administered questionnaire was distributed to 275 patients with IRD who underwent genetic testing after clinical consultation and genetic counseling to investigate the motivations for genetic testing, benefits, challenges, status of communication of results to family, and attitude to timing of genetic testing. In total, 228 (82.9%) responses were analyzed. Several major motivations for genetic testing were identified, including gaining information on future treatment options and clarification of the inheritance pattern, among others. No association was found between the sharing of results with family members and the results of genetic testing. Moreover, according to patients who received positive results, the benefits of genetic testing included information on the inheritance pattern, additional information on the diagnosis, and mental preparation for the future. Even patients who received negative or inconclusive (variant of uncertain significance) results reported certain informative and psychological benefits. Altogether, these findings suggest that provisions for genetic testing and genetic counseling are necessary within a certain period after clinical diagnosis and it is necessary to facilitate appropriate family communication about genetic testing results while paying attention to the background of family relationships. Moreover, the benefits of genetic testing can be influenced by the careful interpretation and information provided on the test results during genetic counseling and consultation.
Preoperative Prediction of Axillary Lymph Node Metastasis in Breast Cancer Using CNN Based on Multiparametric MRI
Authors: Wang Zijian , Sun Hang , Li Jing , Chen Jing , Meng Fancong , Li Hong , Han Lu , Zhou Shi , Yu Tao
Published: February 2022

Background

Multiparametric magnetic resonance imaging (MRI) is widely used in breast cancer screening. Accurate prediction of the axillary lymph nodes metastasis (ALNM) is essential for breast cancer surgery and treatment. However, there is no mature and effective discerning method for ALNM based on multiparametric MRI.

Purpose

To evaluate the ALNM using T1‐weighted imaging (T1WI), T2‐weighted imaging (T2WI), and diffusion‐weighted imaging (DWI) sequences, respectively, and construct a quantitative ALNM discerning model of integrated multiparametric MRI.

Study Type

Retrospective.

Population

Three‐hundred forty‐eight breast cancer patients, 163 with ALNM (99.39% females), and 185 without ALNM (100% females). The dataset was randomly divided into the training set (315 cases) and the testing set (33 cases).

Field Strength/Sequence

1.5 T; T1WI (VIBRANT), T2WI (FSE), and DWI (echo planar imaging [EPI]).

Assessment

The lesion region of interest images were cropped and sent to a pretrained ResNet50 network. Then, the results of different sequences were sent to a classifier for ensemble learning to construct the ALNM model of multiparametric MRI.

Statistical Tests

Performance indicators such as accuracy, the receiver operating characteristic (ROC) curve, and the area under the ROC curve (AUC) were calculated. Student's t‐test, chi‐square test, Fisher's exact test, and Delong test were performed, and P < 0.05 was considered statistically significant.

Results

T2WI performed the best among the three sequences, and achieved the accuracy and AUC of 0.933/0.989 in the testing set. Compared to T1WI with the accuracy and AUC of 0.691/0.806, the increase is significant. While compared to DWI with the accuracy and AUC of 0.800/0.910, the improvement is not significant (P = 0.126). After integrating three sequences, the accuracy and AUC improved to 0.970 and 0.996.

Data Conclusion

T2WI performed better than DWI and T1WI in discerning ALNM in this breast cancer dataset. The proposed quantitative model of integrated multiparametric MRI could effectively help the ALNM diagnosis.

Level of Evidence

1

Technical Efficacy Stage

2
Diffusion‐Weighted Imaging Distinguishes Between Osteomyelitis, Bone Marrow Edema, and Healthy Bone on Forefoot Magnetic Resonance Imaging
Authors: Kruk Konrad A. , Dietrich Tobias J. , Wildermuth Simon , Leschka Sebastian , Toepfer Andreas , Waelti Stephan , Kim Chan‐Hi Olaf , Güsewell Sabine , Fischer Tim
Published: February 2022

Background

Diagnosis of osteomyelitis by imaging can be challenging. The feasibility of diffusion‐weighted imaging (DWI) as ancillary sequence was evaluated in this study.

Purpose

To evaluate DWI for differentiation between osteomyelitis, bone marrow edema, and healthy bone on forefoot magnetic resonance imaging (MRI).

Study type

Prospective.

Subjects

A total of 60 consecutive patients undergoing forefoot MRI divided into three study groups (20 subjects each): osteomyelitis, bone marrow edema, and healthy bone.

Field strength/Sequence

A 1.5T and 3T MRI scanners; readout‐segmented multishot echo planar DWI.

Assessment

Two independent radiologists measured apparent diffusion coefficient (ADC) values within abnormal or healthy bone.

Statistical Tests

ADC values were compared between groups (pairwise t‐test with Bonferroni‐Holm correction for multiple testing). Intraclass correlation coefficient (ICC) was calculated to assess inter‐reader agreement. Threshold ADC values were determined as the cutoffs that maximized the sum of sensitivity and specificity. Receiver operating characteristic (ROC) analysis was performed with statistical threshold of P < 0.05.

Results

Inter‐reader agreement was 0.92 in the healthy bone group and 0.78 in both the edema and osteomyelitis groups. Average ADC values were significantly different between groups: 1432 ± 222 × 10−6 mm2/sec (osteomyelitis), 1071 ± 196 × 10−6 mm2/sec (bone marrow edema), and 277 ± 89 × 10−6 mm2/sec (healthy bone). A threshold ADC value of 534 × 10−6 mm2/sec distinguishes between healthy and abnormal bone with specificity and sensitivity of 100% each. For distinction between osteomyelitis and bone marrow edema, two cutoff values were determined: a 95%‐specificity cutoff indicating osteomyelitis (>1320 × 10−6 mm2/sec) and a 95%‐sensitivity cutoff indicating bone marrow edema (<1155 × 10−6 mm2/sec). Diagnostic accuracy of 95% was achieved for 73% (29/40) of the subjects.

Data Conclusion

DWI with ADC maps distinguishes between healthy and abnormal bone on forefoot MRI. Calculated cutoff values allow confirmation or exclusion of osteomyelitis in a high proportion of subjects.

Evidence Level

2

Technical Efficacy

Stage 2
Characteristics of summer cloud precipitation along latitude 30°N in East Asia derived from Tropical Rainfall Measuring Mission Precipitation Radar and Visible and Infrared Scanner measurements
Authors: Wang Mengxiao , Fu Yunfei , Zhao Chun , Zhong Lei , Li Rui , Wang Dongyong , Qiu Xuexing , Zhou Shengnan
Published: February 2022

There has been little systematic analysis of the influence of the three‐step staircase topography on the characteristics of precipitation along latitude 30°N in East Asia. After the distribution of atmospheric climate states over East Asia was analysed, in this study, the climatological characteristics of summer convective and stratiform precipitation on horizontal distribution, vertical structure, and diurnal variation in East Asia were investigated by using a merged dataset derived from the measurements of the Tropical Rainfall Measuring Mission Precipitation Radar and Visible and Infrared Scanner from 1998 to 2012 reanalysis datasets. Results indicate that the rain frequency, the mean rain rate, and the maximum echo reflectivity factor show clear differences among the three‐step staircase topography, especially between the first staircase and its eastern region. There are small changes in the echo‐top height, the cloud‐top height, the maximum echo reflectivity factor and its corresponding height from the East China Sea westwards to the eastern part of the first staircase, passing the third staircase and the second staircase along 30°N. However, the rain rate decreased obviously twice westwards along this latitude, which responds to aerosol indirect effect and humidity effect, respectively. The diurnal variation of the convective precipitation reflectivity factor indicated that the development of convection in the eastern part of the first staircase gets at the maximum from the early afternoon to sunset, whereas the strongest echo reflectivity factor of precipitation in the second and third staircases including the East China Sea appears in the early morning, which is consistent with the diurnal variations of the atmospheric circulation.
Extension and application of an observation‐based local climate index aimed to anticipate the impact of El Niño–Southern Oscillation events on Colombia
Authors: Sayol Juan‐Manuel , Vásquez Laura M. , Valencia Jorge L. , Linero‐Cueto Jean R. , García‐García David , Vigo Isabel , Orfila Alejandro
Published: February 2022

The Tumaco multivariate index (TMI) is a multidecadal monthly index constructed with unique time series of sea surface temperature, surface air temperature and rain measured at Tumaco bay, in the southern Pacific coast of Colombia, and available since 1961. In this work, this index is re‐evaluated after the addition of in situ sea level data, and its properties for different standardization periods are compared against oceanic El Niño–Southern Oscillation (ENSO) and other derived indices. In particular, we propose a modified TMI, hereinafter referred as TMI4, whose potential to identify the expected sign and the amount of future variations of rain induced by ENSO events in Colombia is analysed for selected extreme episodes. Results indicate that after the inclusion of sea level data, TMI4 can anticipate the development of El Niño events before the ENSO 3 and some other sea surface temperature‐based regional indices, although its predictability depends on the ENSO type (canonical or Modoki). The explanation is that sea level includes new information into TMI4 on the onset of El Niño events. In particular, the signal of intraseasonal sea level anomalies carried by downwelling Kelvin waves is detected at Tumaco tide‐gauge. Moreover, the analysis of the differences, both in magnitude and spatial distribution, of rainfall anomalies induced by positive (El Niño) and negative (La Niña) ENSO events characterized by TMI4 are regionally presented. As a result, we find that TMI4 is especially suited for extensive northern and western areas of mainland Colombia. For completeness, in the appendix we briefly introduce the semi‐automated implementation of TMI4, including a visual interface, which is currently being tested by personnel within the operational oceanography area at Centro de Investigaciones Oceanográficas e Hidrográficas del Pacífico (Dimar‐CCCP).
Unravelling the backbone of climate networks from the analysis of collective dynamics and time reversal
Authors: Naghipour Leyla , Aalami Mohammad Taghi , Nourani Vahid
Published: February 2022

Many complex systems are characterized by interconnected units often difficult, or even impossible, to map through direct observations, while the dynamics of units is mostly easier to measure. The reconstruction of an unknown structure from the observed dynamics is a typical inverse problem in network‐based approaches to overcome such obstacles. However, this procedure is affected by the interplay between the structure and dynamics, as well as by the choice of the statistical method. In this study, collective behaviour of the Earth's climate system was investigated by focusing on three distinct climatological variables in monthly time step using a causality measure to separately construct climate networks through a robust statistical analysis. Multiplex network (MUX) was used to integrate the information obtained from collective dynamics and time reversal for better filtering spurious connectivity. In fact, the proposed approach mitigates undesired effects of pairwise statistical inference by adjusting for unphysical relationships in two layers of the constructed networks. The results indicate that the mere existence of statistical errors allowed by the hypothesis testing lead, inevitably, to reconstruct spurious connections in the null models even when the collective dynamics consists of white‐noise datasets from uncoupled units. The impact of spurious connections with the MUX dynamics is not remarkable to reconstruct the underlying plausible interactions; therefore, the concepts of MUX might be employed with the statistical analysis to unravel the backbone of climate networks. In this way that the inferred connections could distinguish highly connected regions for better understanding interconnected dynamical patterns, yielding deep insights into underlying physical interactions between the oceans and atmosphere. More specifically, edge directionality features provide a complementary tool for analysing topology of the networks with respect to the climatological variables, identifying relevant patterns in the climate system.
Characterization of seasons over the extratropics based on the annual daily mean temperature cycle
Authors: López‐Franca Noelia , Sánchez Enrique , Menéndez Claudio , Carril Andrea F. , Zaninelli Pablo G. , Flombaum Pedro
Published: February 2022

A proposal to characterize seasons based on the annual cycle of daily mean temperature over extratropical regions is presented. Four metrics are computed, based on the dates along the year when the maximum and minimum temperature values and the maximum warming and cooling (when the rate of temperatura change is maximum or minimum) are obtained. These four metrics are computed for 1980–2014 period for ERA‐Interim, JRA‐55 and NCEP2 reanalysis products. Results indicate that these four metrics are able to represent, with geographical coherence over any extratropical region, the start and end of subperiods along the year and that can be seen and used as a consistent procedure to define seasons. The two more extreme metrics (dates for the maximum and minimum temperature) are closely influenced by the variability of the net radiation and near‐surface circulation. Regions with different climatic regimes, defined in terms of land–atmosphere coupling conditions, have different contributing factors influencing the interannual variability of the metrics. In humid regions the net surface radiation is critical for the timing of the maximum temperature date, while the variability of the atmospheric circulation is relevant for the minimum temperature metric. In transitional regions, land–atmosphere interaction plays a key role in the timing of the annual cycle, both in summer and winter. Variations in net radiation are relevant for dry regions. Therefore, a robust methodology to establish seasons based on the annual temperature cycle is presented. We also inspect how the metrics timing responds in terms of the interannual variations of different relevant atmospheric variables.
Rapid antibody conformational screening by matrix‐assisted laser desorption/ionization hydrogen‐deuterium exchange mass spectrometry
Authors: Mukherjee Debopreeti , Trigo‐Mouriño Pablo , Jiang Yuan , Nowak Timothy , Shchurik Vladimir , Adpressa Donovon A. , Louie Michael T. , Reynolds Shane R. , Hohn Michael J. , Al‐Sayah Mohammad Ahmed , Pirrone Gregory F. , Makarov Alexey A.
Published: February 2022

Recent advances in the field of cancer biology have accelerated the discovery and development of novel biopharmaceuticals. At the forefront of these drug development efforts are high‐throughput screening, compressed timelines, and limited sample quantities, all characteristic of the discovery space. To meet program targets, large numbers of protein variants must be produced, screened, and characterized, presenting a daunting analytical challenge. Additionally, the higher‐order structure is paramount for protein function and must be monitored as a critical quality attribute. Matrix‐assisted laser desorption/ionization mass spectrometry has been utilized as an ultra‐fast, automatable, sample‐sparing analytical tool for biomolecules. Our group has published applications integrating hydrogen‐deuterium exchange mass spectrometry with matrix‐assisted laser desorption/ionization mass spectrometry for the rapid conformational characterization of small proteins, the current work expands this application to monoclonal and bi‐specific antibodies. This study demonstrates the ability of the methodology, matrix‐assisted laser desorption/ionization hydrogen‐deuterium exchange mass spectrometry, to detect conformational differences between bi‐specific antibodies from different expression hosts. These conformational differences were validated by orthogonal techniques including circular dichroism, nuclear magnetic resonance, and size‐exclusion chromatography hydrogen‐deuterium exchange mass spectrometry. This work demonstrates the utility of applying the developed methodology as a rapid conformational screening tool to triage samples for further analytical characterization.
MRI imaging versus histologic volumetric estimation of residual injection laryngoplasty material
Authors: Bowen Andrew Jay , San‐Marina Serban , Hunter Danielle , Voss Stephen , Bartemes Kathleen , Macura Slobodan , Meloche Ryan , Spragg Andrew Mearns , Lohse Christine , Oldenburg Michael S. , Ekbom Dale C.
Published: February 2022

Objectives

To examine the degree of agreement between MRI and histologically generated volumetric measurements of residual injection laryngoplasty material.

Methods

Following left recurrent laryngeal nerve transection, rabbit vocal cords were injected with jellyfish collagen, Cymetra®, or Restylane®. Laryngeal tissue was harvested 4 or 12 weeks post injection followed by MRI imaging and histologic cross‐sectioning. Two raters estimated the volume of remaining injection material in specimens within MRI and histologic axial cross sections. Wilcoxon signed rank tests were employed to detect gross differences between inter‐rater measurements and between imaging modalities across time. Agreement between rater measurements and imaging (histology and MRI) was assessed using intra‐class correlation coefficients.

Results

Data was available from 16 rabbits sacrificed at 4 weeks (n = 8) and 12 weeks (n = 8). Inter‐rater testing of MRI imaging revealed no significant differences (p > .05) between rater measurements across time points, and excellent agreement (0.93; 95% confidence interval 0.80–0.98) while histologically estimated volumes demonstrated a significant difference at 4 weeks (p < .05) and overall good agreement (0.89; 95% confidence interval 0.59–0.97). Comparison of MRI and histologically estimated volume measurements revealed significant differences at the 4‐week time point (p < .05) but not at 12 weeks (p > .05). Overall, there is only moderate agreement between MRI and histology estimates (0.72; 95% confidence interval 0.22–0.90).

Conclusions

MRI imaging demonstrates good reliability and similar estimates of volume to histologically estimated measurements of residual injection laryngoplasty material at time points clinically relevant for future injection laryngoplasty experiments.

Level of Evidence

NA.
A Nonisocyanate Strategy toward Polyurethane Vitrimers from Alkylene Bisurea and Epoxide through Eutectic‐Assisted Melting
Authors: Xie Kangzhou , Tang Donglin , Zhang Guangzhao
Published: February 2022

Nonisocyanate polyurethanes (NIPUs) are nowadays considered as green alternatives to conventional polyurethanes, without using the toxic isocyanates. NIPUs usually are synthesized from cyclic carbonates and di(poly)amines. Herein a novel pathway toward polyurethane vitrimers (PUVs) based on epoxide (1,4‐butanediol diglycidyl ether, BDE) and alkylene bisureas (BUs) is reported, which can easily be prepared from renewable urea and diamines. Due to the high melting temperature and the poor solubility, BUs are rarely applied in the synthesis of polyurethanes. To enhance the mellability of BUs, ZnCl2 is introduced to form eutectic system and therefore to assist melting of BUs (eutectic‐assisted melting). When 100 mol% of ZnCl2 is added, BUs are able to melt at 130 °C at which polymerization between BUs and BDE is then triggered and can be finished within 10 min. Interestingly, the obtained polymers are found to be polyurethane vitrimers, for which the relationship between the relaxation time (τ*) and the temperature (T) fits with Arrhenius equation. PUV‐10 samples before and after reprocessing remains similar appearance and mechanical properties (E: ≈90 MPa; σb: ≈17 MPa; εb: ≈200%). A new synthetic strategy is apparently offered here for NIPUs and even for PUVs without adding any crosslinker.
In Vitro Faecal Fermentation of Monomeric and Oligomeric Flavan‐3‐ols: Catabolic Pathways and Stoichiometry
Authors: Di Pede Giuseppe , Bresciani Letizia , Brighenti Furio , Clifford Michael N. , Crozier Alan , Del Rio Daniele , Mena Pedro
Published: February 2022

Scope

The study evaluates the influence of flavan‐3‐ol structure on the production of phenolic catabolites, principally phenyl‐γ‐valerolactones (PVLs), and phenylvaleric acids (PVAs).

Methods and Results

A set of 12 monomeric flavan‐3‐ols and proanthocyanidins (degree of polymerization (DP) of 2–5), are fermented in vitro for 24 h using human faecal microbiota, and catabolism is analyzed by UHPLC‐ESI‐MS/MS. Up to 32 catabolites strictly related to microbial catabolism of parent compounds are detected. (+)‐Catechin and (−)‐epicatechin have the highest molar mass recoveries, expressed as a percentage with respect to the incubated concentration (75 µmol L–1) of the parent compound, for total PVLs and PVAs, both at 5 h (about 20%) and 24 h (about 40%) of faecal incubation. Only A‐type dimer and B‐type procyanidins underwent the ring fission step, and no differences are found in total PVL and PVA production (≃1.5% and 6.0% at 5 and 24 h faecal incubation, respectively) despite the different DPs.

Conclusion

The flavan‐3‐ol structure strongly affects the colonic catabolism of the native compounds, influencing the profile of PVLs and PVAs produced in vitro. This study opens new perspectives to further elucidate the colonic fate of oligomeric flavan‐3‐ols and their availability in producing bioactive catabolites.
Low‐loss X‐band waveguide bandpass filter based on rectangular resonators
Authors: Nimehvari Varcheh Hamed , Rezaei Pejman
Published: February 2022

This paper presents a procedure for designing and synthesizing a 5th‐order waveguide bandpass filter based on rectangular resonators in X‐band frequency. The designed bandpass filter is implemented in waveguide technology with multiple rectangular cavity resonators. Computerized numerical control (CNC) micro‐machined metallic is used in the waveguide filter structure with an accuracy of 0.2 mm. silver plating has been performed inside the X‐band bandpass filter, which has improved the quality of the response. This low‐loss and high‐power X‐band wideband waveguide filter with center frequency at 9.45 GHz, the bandwidth of 0.9 GHz, the return loss of 18 dB, and the insertion loss of 0.08 dB has been realized.
Intraradiological pathology‐calibrated electrical impedance spectroscopy in the evaluation of excision‐required breast lesions
Authors: Mahdavi Reihane , Mehrvarz Sajad , Hoseinpour Parisa , Yousefpour Narges , Abbasvandi Fereshte , Tayebi Mahtab , Ataee Hossein , Parniani Mohammad , Abdolhoseini Saeed , Hajighasemi Farzane , Nourinejad Zeinab , Shojaeian Fateme , Ghafari Hadi , Nikshoar Mohammad Saeed , Abdolahad Mohammad
Published: February 2022

Purpose

Evaluating a real‐time complementary bioelectrical diagnostic device based on electrical impedance spectroscopy (EIS) for improving breast imaging‐reporting and data system (BI‐RADS) scoring accuracy, especially in high‐risk or borderline breast diseases. The primary purpose is to characterize breast tumors based on their dielectric properties. Early detection of high‐risk lesions and increasing the accuracy of tumor sampling and pathological diagnosis are secondary objectives of the study.

Methods

The tumor detection probe (TDP) was first applied to the mouse model for electrical safety evaluations by electrical current measurement. Then it was utilized for characterization of 138 human palpable breast lesions that were to undergo core needle biopsy (CNB), vacuum‐assisted biopsy (VAB), or fine needle aspiration (FNA) on the surgeon's requests. Impedance phase slope (IPS) in frequency ranges of 100– 500 kHz and impedance magnitude in f = 1 kHz were extracted as the classification parameters. Consistency of radiological and pathological declarations for the excisional recommendation was then compared with the IPS values.

Results

Considering pathological results as the gold standard, meaningful correlations between IPS and pathophysiological status of lesions recommended for excision (such as atypical ductal hyperplasia, papillary lesions, complex sclerosing adenosis, and fibroadenoma) were observed (p < 0.0001). These pathophysiological properties may include cell size, membrane permeability, packing density, adenosis, cytoplasm structure, etc. Benign breast lesions showed IPS values greater than 0, while high‐risk proliferative, precancerous, or cancerous lesions had negative IPS values. Statistical analysis showed 95% sensitivity with area under the curve (AUC) equal to 0.92.

Conclusion

Borderline breast diseases and high‐risk lesions that should be excised according to standard guidelines can be diagnosed with TDP before any sampling process. It is an important outcome for high‐risk lesions that are radiologically underestimated to BI‐RADS3, specifically in younger patients with dense breast masses that present challenges in mammographic and sonographic evaluations. Also, the lowest IPS value detects the most pathologic portions of the tumor for increasing sampling accuracy in large tumors.

Significance

Precise detection of high‐risk breast masses, which may be declared BI‐RADS3 instead of BI‐RADS4a
LDVoxelMorph: A precise loss function and cascaded architecture for unsupervised diffeomorphic large displacement registration
Authors: Yang Jing , Wu Yinghao , Zhang Dong , Cui Wenting , Yue Xiaoli , Du Shaoyi , Zhang Hongmei
Published: February 2022

Purpose

The traditional learning‐based non‐rigid registration methods for medical images are trained by an invariant smoothness regularization parameter, which cannot satisfy the registration accuracy and diffeomorphic property simultaneously. The diffeomorphic property reflects the credibility of the registration results.

Method

To improve the diffeomorphic property in 3D medical image registration, we propose a diffeomorphic cascaded network based on the compressed loss (CL), named LDVoxelMorph. The proposed network has several constituent U‐Nets and is trained with deep supervision, which uses a different spatial smoothness regularization parameter in each constituent U‐Nets for training. This cascade‐variant smoothness regularization parameter can maintain the diffeomorphic property in top cascades with large displacement and achieve precise registration in bottom cascades. Besides, we develop the CL as a penalty for the velocity field, which can accurately limit the velocity field that causes the deformation field overlap after the velocity field integration.

Results

In our registration experiments, the dice scores of our method were 0.892 ± 0.040 on liver CT datasets SLIVER37, 0.848 ± 0.044 on liver CT datasets LiTS38, 0.689 ± 0.014 on brain MRI datasets LPBA38, and the number of overlapping voxels of deformation field were 325, 159, and 0, respectively. Ablation study shows that the CL improves the diffeomorphic property more effectively than increases.

Conclusion

Experiment results show that our method can achieve higher registration accuracy assessed by dice scores and overlapping voxels while maintaining the diffeomorphic property for large deformation.
Psychosocial function of Dutch children with cancer and their caregivers during different phases of the COVID‐19 pandemic
Authors: van Gorp Marloes , Maurice‐Stam Heleen , Teunissen Layla C. , Kilsdonk Ellen , van Dijk Jennifer , Sulkers Mirjam , Tissing Wim J. E. , van Litsenburg Raphaële R. L. , Grootenhuis Martha A.
Published: February 2022

We compared psychosocial functioning of children with cancer and their caregivers in several phases of the coronavirus disease 2019 (COVID‐19) pandemic to before COVID‐19. One or more questionnaires on health‐related quality of life (HRQoL) or fatigue of children or distress of their caregivers was available from 1644 families. In children with cancer, HRQoL was stable throughout the COVID‐19 pandemic. Fatigue was slightly lower and sleep somewhat better during the pandemic than before. Caregiver distress was lower in the first pandemic phase, but increased to pre‐COVID‐19 levels in later phases, indicating that the length and consequences of the pandemic may be weighing on them.
Exploration of genetic ancestry and socioeconomic status in the incidence of neuroblastoma: An ecological study
Authors: Jung Eun Mi , Johnson Rebecca A. , Hubbard Aubrey K. , Spector Logan G.
Published: February 2022

Although global differences in the incidence of neuroblastoma have been examined, the underlying mechanism has yet to be elucidated. Previous studies have suggested genetic ancestry and human development index (HDI) as contributing factors, but few studies have been conducted at the international level. Here, we aimed to examine whether the frequency of common genomic variation associated with neuroblastoma can affect its risk at the ecological level with consideration of the HDI. Minor allele frequencies (MAFs) for 22 single‐nucleotide polymorphisms (SNPs) were abstracted from the Geography of Genetic Variants Browser. The number of incident neuroblastomas for each population was obtained from the Cancer Incidence in Five Continents series. Further, population pseudo‐polygenic risk scores (pp‐PRSs) were calculated as a sum of MAFs at the population level, each of which was weighted by effect sizes from prior studies. Negative binomial regression was used to estimate the incidence rate ratios (IRRs) and the 95% confidence intervals (CIs) to examine whether differences in MAFs across the population influence the risk of neuroblastoma, with and without adjustment for HDI and whether pp‐PRSs can be a predictor of the risk of neuroblastoma. Overall, our results indicated that the neuroblastoma risk associated with variation in SNP frequency could not be differentiated from that of HDI at the ecological level. Additionally, pp‐PRSs were not significantly associated with the risk of neuroblastoma (IRR: 0.99, 95% CI: 0.62–1.60). Further study using individual‐level data is warranted to minimize the bias related to the use of population‐level data in this study.
Magnesium hydroxide micro‐whiskers as super‐reinforcer to improve fire retardancy and mechanical property of epoxy resin
Authors: Li Na , Li Zhi , Liu Zhiqi , Yang Yunxian , Jia Yuchen , Li Jisheng , Wei Ming , Li Lijuan , Wang De‐yi
Published: February 2022

Aiming to endow the efficient fire safety to epoxy resin (EP), magnesium hydroxide micro‐whiskers (mw‐MH) as super‐reinforcement were incorporated into EP. The thermal kinetics of EP/mw‐MH micro‐composites were investigated. The limited oxygen index (LOI) of EP with the incorporation of mw‐MH reached up to 33.7% greatly improved comparing to 26.3% of pristine EP. The cone calorimeter test (CCT) showed the heat release rate (HRR), smoke production rate (SPR) of the EP/3mw‐MH with the addition of 3 wt% mw‐MH obviously reduced, as evidenced by the reduction of peak of HRR and SPR for the micro‐composites to 58% and 48%, respectively. Moreover, improvements were also observed in total heat release (THR) and total smoke production (TSP) of EP/3mw‐MH, which were decreased by 29% and 34% at 300 s. Compared with common used industrial magnesium hydroxide (ind‐MH), EP/mw‐MH micro‐composites possessed excellent fire safety performance at the same loading, which was attributed to the jammed network structure. Furthermore, the Young's modulus and tensile strength of EP/mw‐MH micro‐composites maintained. Finally, further investigation was proposed to explain the flame retardant mechanism, which involved the jammed network structures at internal and compact protective char. The magnesium hydroxide with one‐dimensional structure offered an effective method to improve the fire retardancy of polymers.
Prenatal imaging features related to RAC3 pathogenic variant and differential diagnoses
Authors: Cabet Sara , Vasiljevic Alexandre , Putoux Audrey , Labalme Audrey , Sanlaville Damien , Chatron Nicolas , Lesca Gaetan , Guibaud Laurent
Published: February 2022

Key points

What’s already known about this topic?

Six individuals between 5‐ and 19‐year‐old were reported with pathogenic variants in RAC3 responsible for brain malformations involving midline.

What does this study add?

RAC3‐fetopathy is associated with fetal akinesia deformation sequence, and complex brain malformations including corpus callosum agenesis, diencephalosynapsis, kinked brainstem, and vermian hypoplasia.

The differential diagnoses with prenatal kinked brainstem include fetopathies related to KIAA1109, L1CAM, Walker‐Warburg syndrome and tubulinopathies. The present report adds the RAC3 related condition to this list.
Fluorophore‐mediated photooxidation of the guanine heterocycle
Authors: Fleming Aaron M. , Xiao Songjun , Chabot Michael B. , Burrows Cynthia J.
Published: February 2022

Fluorescent dyes are routinely used to visualize DNA or RNA in various experiments, and some dyes also act as photosensitizers capable of catalyzing oxidation reactions. The present studies explored whether the common labeling dyes fluorescein, rhodamine, BODIPY, or cyanine3 (Cy3) can function as photosensitizers to oxidize nucleic acid polymers. Photoirradiation of each dye in the presence of the guanine (G) heterocycle, which is the most sensitive toward oxidation, identified slow rates of nucleobase oxidation in the nucleoside and DNA contexts. For all four fluorophores studied, the only product detected was spiroiminodihydantoin (Sp), suggesting that the dyes functioned as Type II photosensitizers and generate singlet oxygen (1O2). The nucleoside reactions were then conducted in D2O solutions, known to increase the lifetime of 1O2, which resulted in an ~6‐fold increase in the Sp yield, further supporting the classification of these dyes as Type II photosensitizers. Lastly, we inspected the pattern of G reactivity with the dyes upon photoirradiation in the context of a parallel‐stranded G quadruplex. The G nucleotides in the two exterior G tetrads were found to be oxidation prone, providing the third line of evidence that the dyes are Type II photooxidants. The present work found that the common dyes fluorescein, rhodamine, BODIPY, or Cy3 can drive G oxidation but with a slow rate and low overall yield. This will likely not impact many experiments using dyes to study nucleic acids except for those that have long exposures with high‐intensity lights, such as sequencing‐by‐synthesis experiments using fluorescence as the readout.
Identification and integrative analysis of microRNAs in myelodysplastic syndromes based on microRNAs expression profile
Authors: Ma Limin , Yang Haiping , Yang Xuewen
Published: February 2022

Myelodysplastic syndromes (MDS) are a group of malignant hematological disorders characterized by the abnormal development of hematopoietic stem cells and increased risk of acute myelogenous leukemia. Although the pathogenesis of MDS has not been fully understood, various alterations of microRNAs (miRNAs) have been reported in MDS. This study aimed to explore the molecular mechanisms of MDS by integrative bioinformatics analysis of miRNAs expression profile. The GSE81372 expression profile dataset was downloaded from Gene Expression Omnibus database. The differentially expressed miRNAs (DEMs) between MDS and normal controls were identified and targets of miRNAs were predicted. Subsequently, gene ontology (GO) functional and pathway enrichment analyses of target genes were performed. Finally, pathway relation network and miRNA–GO regulatory network were constructed and analyzed. A total of six upregulated and 35 downregulated DEMs were identified. The results showed that target genes of DEMs mainly participated in the process of signal transduction, blood coagulation, apoptotic process, cell proliferation, transmembrane transport, and angiogenesis. The significantly enriched pathways included MAPK signaling pathway, PI3K‐Akt signaling pathway, TGF‐beta signaling pathway, Hippo signaling pathway, and P53 signaling pathway. Moreover, miR‐195‐5p, miR‐4505, miR‐22‐3p, and miR‐148a‐3p were selected as hub miRNAs in miRNA–GO regulatory network and their aberrant expression might be closely associated with MDS pathogenesis. Our discovery provides a registry of miRNAs and pathways that are disrupted in MDS, which has the potential to be used in clinic for diagnosis and target therapy of MDS in future.
Development and implementation of an “Internet+” management plan for cancer patients with wounds/stomas during the coronavirus disease 2019 pandemic
Authors: Niu Niu , Zhi Xiaoxu , Zhang Liuliu , Wang Meixiang , Zhao Yun , Yang Lifang , Wu Bing , Zhu Ping , Wang Na , Zhang Maomao , Wu Bainv , Zhang Yinan , Meng Aifeng
Published: February 2022

To explore the practical application and effect of the management plan for cancer patients with wounds/stomas based on the “Internet+” model during the coronavirus disease 2019 (COVID‐19) pandemic. Based on the specific situation during the COVID‐19 pandemic, we established the “Internet+” management team for cancer patients with wounds/stomas. After systematical literature search and brainstorming analysis, we developed a management plan for cancer patients with wounds/stomas based on the “Internet+” model. Then, we included cancer patients with wounds/stomas who needed follow‐up visits or consultations at Jiangsu Cancer Hospital from January 25 to April 30, 2020. A total of 304 patients were participated in the study. The effects of the plan were evaluated including patient satisfaction, the proportion of patients who did not need to go to the hospital for treatment, the proportion of patients with improved symptoms and the rate of the patients or nurses contracted COVID‐19. After the implementation of the plan, 56.3% of the patients mastered the relevant self‐care methods under the guidance of specialist nurses and did not need to go to the hospital for treatment. A total of 89.5% of the patients showed improvement in symptoms, and 99.4% of the patients were satisfied with the online treatment. None of the patients or nurses contracted COVID‐19. The “Internet+” management plan for cancer patients with wounds/stomas during the COVID‐19 pandemic had supported epidemic prevention and control in medical institutions and reduced the risk of cross infection. In addition, this type of plan effectively improved disease symptoms in the patients, and their level of satisfaction was high.
Sensitivity of dose‐estimations for acute acetaminophen overdose in predicting hepatotoxicity risk using the Rumack‐Matthew Nomogram
Authors: Chomchai Summon , Mekavuthikul Pattaraporn , Phuditshinnapatra Jariya , Chomchai Chulathida
Published: February 2022

Timely assessment of acetaminophen concentration in overdose situations is not always available in resource‐poor settings. The 150 mg/kg dose‐estimate for acetaminophen is widely considered as criterion for acetaminophen overdose. Its sensitivity and specificity when compared to the 150 mg/L treatment line on the Rumack‐Matthew Nomogram (150‐treatment line) has rarely been evaluated. This is a retrospective chart review of acute acetaminophen overdose patients. We evaluated the sensitivity and specificity of the 150, 200 mg/kg and 8‐ and 10‐g dose‐estimates by plotting the serum acetaminophen levels and using 150‐treatment line on the Nomogram as the treatment cut‐off. A comparison of medical care costs was performed. We enrolled 784 cases for analysis. Median (IQR) age was 23 (20–28) years (81.9% female). There were 545 cases (69.5%) where the estimated ingested acetaminophen dose were ≥150 mg/kg and 406 cases (51.8%) with concentrations ≥150‐treatment line. Hepatotoxicity and acute liver injury (ALI) occurred in 7.3% and 23.9%, respectively. The sensitivity and specificity of 150 mg/kg dose‐estimate for the 150‐treatment line were 92.6% (95% CI 89.6, 94.8) and 55.3% (95% CI 50.3, 60.2). Among patients with dose‐estimate below150 mg/kg, none developed hepatotoxicity and 17 (7.1%) develop ALI. The administration of activated charcoal significantly decreased the risk of being above the 150‐treatment line by half. In resource‐poor setings, the use of 150 mg/kg dose‐estimate as a stand‐alone criteria for initiation of N‐acetylcysteine therapy is satisfactory, especially when combined with decontamination with activated charcoal and follow up of aminotransferase at 24 h.
Systems analysis shows that thermodynamic physiological and pharmacological fundamentals drive COVID‐19 and response to treatment
Authors: Head Richard J. , Lumbers Eugenie R. , Jarrott Bevyn , Tretter Felix , Smith Gary , Pringle Kirsty G. , Islam Saiful , Martin Jennifer H.
Published: February 2022

Why a systems analysis view of this pandemic? The current pandemic has inflicted almost unimaginable grief, sorrow, loss, and terror at a global scale. One of the great ironies with the COVID‐19 pandemic, particularly early on, is counter intuitive. The speed at which specialized basic and clinical sciences described the details of the damage to humans in COVID‐19 disease has been impressive. Equally, the development of vaccines in an amazingly short time interval has been extraordinary. However, what has been less well understood has been the fundamental elements that underpin the progression of COVID‐19 in an individual and in populations. We have used systems analysis approaches with human physiology and pharmacology to explore the fundamental underpinnings of COVID‐19 disease. Pharmacology powerfully captures the thermodynamic characteristics of molecular binding with an exogenous entity such as a virus and its consequences on the living processes well described by human physiology. Thus, we have documented the passage of SARS‐CoV‐2 from infection of a single cell to species jump, to tropism, variant emergence and widespread population infection. During the course of this review, the recurrent observation was the efficiency and simplicity of one critical function of this virus. The lethality of SARS‐CoV‐2 is due primarily to its ability to possess and use a variable surface for binding to a specific human target with high affinity. This binding liberates Gibbs free energy (GFE) such that it satisfies the criteria for thermodynamic spontaneity. Its binding is the prelude to human host cellular entry and replication by the appropriation of host cell constituent molecules that have been produced with a prior energy investment by the host cell. It is also a binding that permits viral tropism to lead to high levels of distribution across populations with newly formed virions. This thermodynamic spontaneity is repeated endlessly as infection of a single host cell spreads to bystander cells, to tissues, to humans in close proximity and then to global populations. The principal antagonism of this process comes from SARS‐CoV‐2 itself, with its relentless changing of its viral surface configuration, associated with the inevitable emergence of variants better configured to resist immune sequestration and importantly with a greater affinity for the host target and higher infectivity. The great value of this physiological and pharmacological perspective is that it reveals the fundamental thermodynamic underpinnings of SARS‐CoV‐2 infection.
A systematic review and meta‐analysis of preclinical and clinical studies on the efficacy of ginger for the treatment of fatty liver disease
Authors: Samadi Mehnoosh , Moradinazar Mehdi , Khosravy Tina , Soleimani Davood , Jahangiri Parvin , Kamari Negin
Published: February 2022

Fatty liver disease (FLD) is the most common chronic liver disease worldwide. The pathogenesis of this disease is closely related to obesity and insulin resistance. Ginger has hypolipidemic and antioxidant effects and acts as an insulin sensitizer. This study aims to evaluate the effect of ginger supplementation on the fatty liver. A comprehensive search of Medline/PubMed, Embase, Scopus, Web of Science/ISI, and Cochrane databases was conducted without time or language restrictions. Eighteen eligible studies were identified, including 17 in‐vivo experiments in quantitative analysis and 3 clinical trials in qualitative analysis. The present study provides comprehensive evidence of the efficacy of ginger to improve the liver levels of cholesterol (−5.60 mg/g), triglycerides (TG, −4.28 mg/g), malondialdehyde (−3.16 nmol/mg), catalase (CAT) (3.35 nmol/mg), superoxide dismutase (SOD, 3.01 U/mg), serum levels of alanine aminotransferase (ALT, −2.85 U/L), aspartate aminotransferase (AST, −0.98 U/L), TG (−4.98 mg/dL), low‐density lipoprotein (LDL, −3.94 mg/dL), total cholesterol (TC, −3.45 mg/dL), high‐density lipoprotein (HDL, 1.27 mg/dL), and fasting blood sugar (FBS, −2.54 mg/dL). Ginger administration may reduce many clinical aspects of FLD by several mechanisms, including insulin‐sensitive effects, stimulating the expression of antioxidant enzymes, reducing the generation of reactive oxygen species (ROS), having antidyslipidemic activities, and reducing hepatic fat content. However, future clinical trials are essential to investigate the clinical application of ginger in this area.
Semi‐global leader–following output consensus of heterogeneous systems with all agents subject to input saturation
Authors: Zhou Panpan , Chen Ben M.
Published: February 2022

In this paper, we consider the semi‐global leader–following output consensus of heterogeneous multi‐agent linear systems over a directed communication graph with both the leader agent and the follower agents subject to input saturation. Via the low gain feedback design technique, both the state feedback and output feedback consensus protocols are constructed. In the state feedback case, a fully distributed observer is given to estimate the state of the leader agent. In the output feedback case, for both the informed follower agents and the uninformed follower agents, a state observer and a distributed leader state observer for each follower are designed to estimate the state of the follower itself and the state of the leader agent, respectively. In the distributed leader state observer, additional discontinuous functions are designed to suppress the influence of the bounded input of the leader agent. In both consensus protocols, a term under a condition similar to that used in the robust control is used to compensate for the control input of the leader agent.