bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Cyclic Polyolefin: Ring‐Opening Metathesis Polymerization by Binuclear Vanadium Complexes†
Authors: Hou Xiaohua , Chen Xiaojian , Gao Xiang , Xu Lei , Zou Hui , Zhou Li , Wu Zong‐Quan
Published: January 2021

Main observation and conclusion

Ring‐opening metathesis polymerization (ROMP) of norbornene by binuclear vanadium alkylidene in‐situ formed from dialkyl complexes was investigated. Higher activities were observed by the binuclear system than mononuclear analogues. Especially the cyclic polymers were obtained and demonstrated. It is proposed that cyclic binuclear vanadium alkylidene was afforded due to the intramolecular chain‐transfer reaction. The size of polymer ring could be adjusted by the vanadium catalyst structure and polymerization temperature. Similar results were also observed in the ROMP of cyclopentene.
On the identification of thyroid nodules using semi‐supervised deep learning
Authors: Turk Gamze , Ozdemir Mustafa , Zeydan Ruken , Turk Yekta , Bilgin Zeki , Zeydan Engin
Published: January 2021

Detecting malign cases from thyroid nodule examinations is crucial in healthcare particularly to improve the early detection of such cases. However, malign thyroid nodules can be extremely rare and is hard to find using the traditional rule based or expert‐based methods. For this reason, the solutions backed by Machine Learning (ML) algorithms are key to improve the detection rates of such rare cases. In this paper, we investigate the application of ML in the healthcare domain for the detection of rare thyroid nodules. The utilized dataset is collected from 636 distinct patients in 99 unique days in Turkey. In addition to the texture feature data of the Ultrasound (US), we have also included the scores of different assessment methods created by different health institutions (e.g., Korean, American and European thyroid societies) as additional features. For detection of extremely rare malign cases, we use auto‐encoder based neural network model. Through numerical results, it is shown that the auto‐encoder based model can result in an average Recall score of 0.98 and a Sensitivity score of 1.00 for detecting malign and non‐malign cases from the healthcare dataset outperforming the traditional classification algorithms that are trained after Synthetic Minority Oversampling Technique (SMOTE) oversampling.
Comparative study of biochar prepared from cow dung and sewage sludge and its application as an adsorbent for organic pollutants removal in water
Authors: Suárez‐Vázquez Santiago Iván , Cruz‐López Arquímedes , Márquez‐Reyes Julia Mariana , Flores Breceda Héctor , García‐Gómez Celestino
Published: January 2021

In this research, the synthesis of biochar from cow dung and sewage sludge and its application for the removal of organic contaminants using methylene blue (MB) as the model molecule was evaluated. Experiments were performed using different concentrations of adsorbent and MB and were optimized by a response surface methodology (RSM). Dynamic models were adjusted to the experimental data and the regeneration of the bed was studied. The results showed that the optimal conditions to favor the adsorption of MB, in a fixed bed and making a comparison between the two biochar sources, were those where an adsorbent biochar concentration of 5 g and initial MB concentration of 10 mg L−1 were used. The biochar prepared from cow dung presented the best adsorption conditions. Under these conditions, the breaking time was 172.73 min. The models of Thomas, Bohart–Adams, and Yoon–Nelson were applied for the study in fixed‐bed columns and it was observed that the models were adjusted satisfactorily. Regeneration was possible for three different cycles, slightly diminishing the performance of the bed with elution of HNO3. These results indicate that MB bed fixed adsorption on cow dung biochar is viable and suitable for water treatment.
A method for estimating sediment budgets of washover deposits using digital terrain models
Authors: Hansen Lars Ø. , Ernstsen Verner B. , Clemmensen Lars B. , Al‐Hamdani Zyad , Kroon Aart
Published: January 2021

Washover fans are located on small barriers in fetch‐limited micro‐tidal coastal environments in Denmark. These washover fans are formed during high‐energy storm events and we present a method to quantify their volumes and to estimate sediment exchanges between washover fans and their adjacent morphologies. We use high resolution digital terrain models (DTMs) based on light detection and ranging (LiDAR) data. We have delineated landforms using known methods of scale analysis and geomorphometric classification. We quantified volumes of the delineated landforms and estimated the related sediment budgets. These computed volumes were compared using different pre‐depositional surfaces. Finally, we assessed the sediment exchange and associated sources of sediments of the washover fans. We applied a scale analysis to determine suitable DTM resolution and focal statistics window size as input to a geomorphometric classification analysis. Landform areas and landforms were delineated using morphometric threshold values, and volumes and sediment budgets of the delineated landforms were computed using different assumptions to define the pre‐depositional surface. Resulting washover fan volumes were validated against digital elevation model (DEM) of difference (DoD) derived volumes. Sediment budgets were derived from representative volumes of the washover fans and adjacent berms. We show that quantification of washover features derived from DTMs, using geomorphometric analysis is feasible and that the presented approach provides estimates of washover deposit volumes with an accuracy between 1% and 28% compared to control volumes. © 2021 John Wiley & Sons, Ltd.
Clinical and laboratory characteristics of severe and non‐severe patients with COVID‐19: A retrospective cohort study in China
Authors: Shi Shaorui , Nie Bin , Chen Xinzu , Cai Qiang , Lin Chunxin , Zhao Guangda , Zhang Xingying
Published: January 2021

Background

Patients diagnosed with the novel coronavirus disease (COVID‐19) who develop severe symptoms need to be determined in advance so that appropriate treatment strategies are in place.

Methods

To determine the clinic features of patients diagnosed definitely with COVID‐19 and evaluate risk factors for severe outcome, the medical records of hospitalized patients were reviewed retrospectively by us and data were compiled. Laboratory data from 90 cases were analyzed, and COVID‐19 patients were classified into two groups (severe and non‐severe) based on the severity.

Results

Severe COVID‐19 cases on admission had higher leukocyte and neutrophil counts, neutrophil‐to‐lymphocyte ratio (NLR), D‐dimer, fibrinogen, C‐reactive protein levels, and lower lymphocyte counts compared with those of non‐severe cases (p < 0.05). The area under the curve (AUC) for leukocyte counts, neutrophil counts, and levels of C‐reactive protein was 0.778, 0.831, and 0.800, respectively. The thresholds were 7.70 × 109/L for leukocyte counts, 5.93 × 10⁹/L for neutrophil counts, and 75.07 mg/L for C‐reactive protein, respectively. Logistic regression analyses indicated that higher white blood cell (WBC) counts (OR, 1.34; 95% CI, 1.05–1.71), neutrophil counts (OR, 1.35; 95% CI, 1.06–1.73), and C‐reactive protein levels (OR, 1.02; 95% CI, 1.0–1.04) were several predictive factors for severe outcome. Severe COVID‐19 patients had a reduction in WBC counts, D‐dimer, C‐reactive protein, and fibrinogen upon discharge from hospital, while lymphocyte counts increased (p < 0.05).

Conclusion

Counts of WBC, neutrophil, and lymphocyte, NLR, and levels of C‐reactive protein, D‐dimer, and fibrinogen are helpful for prediction of the deterioration trend in patients diagnosed with COVID‐19.
USP21 promotes cell proliferation by maintaining the EZH2 level in diffuse large B‐cell lymphoma
Authors: Ma Huixian , Luo Xiangrui , Zhou Peng , He Na , Zhou Jun , Liu Min , Xie Wei
Published: January 2021

Background

Diffuse large B‐cell lymphoma (DLBCL) is the most common category of non‐Hodgkin lymphoma (NHL). However, the underlying molecular mechanism of DLBCL remains unclear.

Methods

Real‐time PCR and Western blot analysis were performed to assess the expression of ubiquitin‐specific peptidase 21 (USP21) or enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2). CCK8 assay and cell death staining were carried out to examine the role of USP21 in cell proliferation and cell death, respectively.

Results

We found that the deubiquitinase USP21 was highly expressed in the DLBCL lymphoid tissue. The expression of USP21 promoted DLBCL cell proliferation, while it had no obvious effect on cell death. In addition, we found that USP21 regulated cell proliferation via cysteine 221, the catalytic site of USP21. Furthermore, we identified that USP21 could stabilize EZH2, a protein required for germinal center formation and lymphoma formation.

Conclusion

The deubiquitinase USP21 promotes cell proliferation by maintaining the EZH2 protein level in DLBCL.
Converting croplands to orchards changes soil microbial community composition and co‐occurrence patterns
Authors: Wang Rui , Wang Ying , Zheng Wei , Hou Fangbin , Hu Yaxian , Guo Shengli
Published: January 2021

Soil microorganisms are key to uncovering the mechanisms driving variation in soil biogeochemical processes associated with land‐use change. A large number of croplands have been converted to orchards on the Chinese Loess Plateau due to the increased economic benefits which result. However, the microbial community and their functional composition remain poorly understood. In this study, soil samples were collected from croplands and orchards. Soil physicochemical properties and the community (represented by 16S rRNA for bacteria and ITS for fungi) were measured, and interactions among species and the soil organic matter (SOM) degradation via microbial metabolism and its associated genes were analyzed. Croplands converted to orchards affected bacterial and fungal community structure by increasing the relative abundance of Proteobacteria, Bacteroidetes, Firmicutes, Actinobacteria, and Ascomycota, whereas it decreased the α‐diversity of bacteria and fungi. The co‐occurrence network was larger and more complex within croplands than within orchards, indicating more extensive interactions and higher community stability potential. The abundance of potential genes related to cellulose and hemicellulose metabolism in orchards was higher than that in croplands, whereas the abundance of genes related to lignin decomposition was lower than that in croplands. In addition, the abundance of saprotrophic and symbiotrophic fungi in orchards was significantly lower than that in croplands (27 and 88%, respectively), whereas the abundance of pathotrophic fungi in orchards was almost six‐times that in croplands. The soil organic carbon (SOC) and soil C:N in orchards were significantly lower than that in croplands. Converting croplands to orchards significantly altered the microbial community composition and their functionality, as well as decreased the complexity of interaction between microorganisms. The decreased SOC and increased soil C:N ratio could be attributed to these variations. Improved management practices should be implemented for the maintenance of soil biodiversity and SOC in orchards to avoid soil degradation and ensure sustainable development.
Dermatologic Scar Assessment With Stereoscopic Imaging and Digital Three‐Dimensional Models: A Validation Study
Authors: Hendel Kristoffer , Ortner Vinzent K. , Fuchs Christine S. K. , Eckhouse Vardit , Haedersdal Merete
Published: January 2021

Background and Objective

We evaluated a new handheld stereoscopic imaging system capable of visualizing scars with digital three‐dimensional (3D) models and providing automated morphometric estimates. The objective was to validate the repeatability and accuracy of intra‐ and inter‐investigator scan results.

Study Design/Materials and Methods

Engineered metal plates with depressed and elevated model scars (n = 72) were scanned six times by one investigator. In vivo hypertrophic and atrophic scars (n = 15) were scanned once by three investigators. The repeatability of morphometric estimates was assessed using coefficients of variation (CVs) to compare the variation among multiple scan results for both models and in vivo scars, with 0% reflecting a perfect match. Scar estimates from digital 3D reconstructions were compared with the known dimensions of physical model scars and with ruler measurements of in vivo scars.

Results

A total of 48 model scars and 12 in vivo scars were eligible for automated analyses with the imaging system's proprietary software. Intra‐investigator scan results for the model scars were repeatable, with low variance for all parameters: volume, area, length, and depth/height (CV: 1.8–3.1%). By comparison, inter‐investigator scans of real in vivo scars resulted in slightly higher median CVs (4.4–7.3%; P < 0.05). 3D model scar estimates correlated well with the known physical dimensions of model scars for all parameters (P < 0.001) and accurately reflected the measurements of in vivo scars (P < 0.001). The six in vivo scars situated on the chest and abdomen showed the highest inter‐investigator variation, due to respiratory movement artifacts.

Conclusion

Stereoscopic imaging of scars generates accurate and repeatable measurement estimates that show little intra‐ and inter‐investigator‐based assessment variation. The best results are achieved by minimizing subject movement. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.
MIND and Mediterranean Diets Associated with Later Onset of Parkinson's Disease
Authors: Metcalfe‐Roach Avril , Yu Adam C. , Golz Ella , Cirstea Mihai , Sundvick Kristen , Kliger Daniel , Foulger Liam H. , Mackenzie Melissa , Finlay B. Brett , Appel‐Cresswell Silke
Published: January 2021

Background

The MIND diet has been linked with prevention of Alzheimer's disease and cognitive decline but has not been fully assessed in the context of Parkinson's disease (PD). The objective of the present study was to determine whether MIND diet adherence is associated with the age of Parkinson's disease onset in a manner superior to that of the Mediterranean diet.

Methods

Food Frequency Questionnaires from 167 participants with PD and 119 controls were scored for MIND and 2 versions of Mediterranean diet adherence. Scores were compared between sex and disease subgroups, and PD diet adherence was correlated with age at onset using univariate and multivariate linear models.

Results

The female subgroup adhered more closely to the MIND diet than the male subgroup, and diet scores were not modified by disease status. Later age of onset correlated most strongly with MIND diet adherence in the female subgroup, corresponding to differences of up to 17.4 years (P < 0.001) between low and high dietary tertiles. Greek Mediterranean adherence was also significantly associated with later PD onset across all models (P = 0.05–0.03). Conversely, only Greek Mediterranean diet adherence remained correlated with later onset across all models in men, with differences of up to 8.4 years (P = 0.002).

Conclusions

This cross‐sectional study found a strong correlation between age of onset of PD and dietary habits, suggesting that nutritional strategies may be an effective tool to delay PD onset. Further studies may help to elucidate potential nutrition‐related sex‐specific pathophysiological mechanisms and differential prevalence rates in PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Differentiating Moebius syndrome and other congenital facial weakness disorders with electrodiagnostic studies
Authors: Lehky Tanya , Joseph Reversa , Toro Camilo , Wu Tianxia , Van Ryzin Carol , Gropman Andrea , Facio Flavia M. , Webb Bryn D. , Jabs Ethylin W. , Barry Brenda S. , Engle Elizabeth C. , Collins Francis S. , Manoli Irini ,   and the Moebius Syndrome Research Consortium
Published: January 2021

Introduction

Congenital facial weakness (CFW) can result from facial nerve paresis with or without other cranial nerve and systemic involvement, or generalized neuropathic and myopathic disorders. Moebius syndrome is one type of CFW. In this study we explored the utility of electrodiagnostic studies (EDx) in the evaluation of individuals with CFW.

Methods

Forty‐three subjects enrolled prospectively into a dedicated clinical protocol and had EDx evaluations, including blink reflex and facial and peripheral nerve conduction studies, with optional needle electromyography.

Results

MBS and hereditary congenital facial paresis (HCFP) subjects had low‐amplitude cranial nerve 7 responses without other neuropathic or myopathic findings. Carriers of specific pathogenic variants in TUBB3 had, in addition, a generalized sensorimotor axonal polyneuropathy with demyelinating features. Myopathic findings were detected in individuals with Carey‐Fineman‐Ziter syndrome, myotonic dystrophy, other undefined myopathies, or CFW with arthrogryposis, ophthalmoplegia, and other system involvement.

Discussion

EDx in CFW subjects can assist in characterizing the underlying pathogenesis, as well as guide diagnosis and genetic counseling.
Insights into specificity and catalytic mechanism of amphotericin B/nystatin thioesterase
Authors: Wang Rufan , Tao Wentao , Liu Lei , Li Chen , Bai Linquan , Zhao Yi‐Lei , Shi Ting
Published: January 2021

Polyene polyketides amphotericin B (AMB) and nystatin (NYS) are important antifungal drugs. Thioesterases (TEs), located at the last module of PKS, control the release of polyketides by cyclization or hydrolysis. Intrigued by the tiny structural difference between AMB and NYS, as well as the high sequence identity between AMB TE and NYS TE, we constructed four systems to study the structural characteristics, catalytic mechanism, and product release of AMB TE and NYS TE with combined MD simulations and quantum mechanics/molecular mechanics calculations. The results indicated that compared with AMB TE, NYS TE shows higher specificity on its natural substrate and R26 as well as D186 were proposed to a key role in substrate recognition. The energy barrier of macrocyclization in AMB‐TE‐Amb and AMB‐TE‐Nys systems were calculated to be 14.0 and 22.7 kcal/mol, while in NYS‐TE‐Nys and NYS‐TE‐Amb systems, their energy barriers were 17.5 and 25.7 kcal/mol, suggesting the cyclization with their natural substrates were more favorable than that with exchanged substrates. At last, the binding free energy obtained with the MM‐PBSA.py program suggested that it was easier for natural products to leave TE enzymes after cyclization. And key residues to the departure of polyketide product from the active site were highlighted. We provided a catalytic overview of AMB TE and NYS TE including substrate recognition, catalytic mechanism and product release. These will improve the comprehension of polyene polyketide TEs and benefit for broadening the substrate flexibility of polyketide TEs.
Clinical efficacy of intravaginal recombinant lysostaphin administration on endometritis in sows
Authors: Ye Guizi , Huang Jinjiang , Li Guodong , Zhang Jien , Sun Yongxue , Zeng Dongping , Bao Wenbin , Zhong Jiang , Huang Qingshan
Published: January 2021

Recombinant lysostaphin has been used for the treatment of cow endometritis and mastitis in China. To our knowledge, no scientific effort has been made to evaluate the efficacy of lysostaphin in sows with clinical endometritis. Lysostaphin, loaded in effervescent tablets that were completely foamed and dissolved within 30 min in the presence of water or body fluids and released active lysostaphin, were administered vaginally on endometritis sows in this study. The clinical recovery, bacterial clearance and reproductive performance of sows with endometritis were investigated. We found that the 400U dosage (400U lysostaphin/pill/time, repeat once on the third day, a total of two times, with 10% oxytetracycline uterine injection as a control) is the most effective treatment. Staphylococcus aureus was the most prevalent finding (34%, n = 188), followed by Streptococcus (32%, n = 181), Escherichia coli (19%, n = 104) and other bacilli (15%, n = 83) before treatment by drugs. Administration of lysostaphin resulted in an extremely significant (p < .01) reduction in S. aureus (0.18 ± 0.25 from 4.57 ± 0.33) and Streptococcus (0.11 ± 0.14 from 3.88 ± 0.29), as well as a significant (p < .05) reduction in E. coli (0.55 ± 0.42 from 3.11 ± 0.14). Mixed infections (83%) were predominant before treatment, in contrast to single infections (61%) after treatment. Large‐scale trials were conducted to verify the clinical efficacy of lysostaphin on sow endometritis. The average cure rate of 400u lysostaphin on sow endometritis(82.5%) was higher than the antibiotic group(72.17%). In addition, our results revealed that intravaginal administration of lysostaphin had no adverse effect on the reproductive performance of sows. Thus, this lysostaphin has potential application value as a new method alternative to antibiotics to treat endometritis in sows.
Genetic dissection of Striga hermonthica (Del.) Benth. resistance via genome-wide association and genomic prediction in tropical maize germplasm
Authors: Gowda Manje , Makumbi Dan , Das Biswanath , Nyaga Christine , Kosgei Titus , Crossa Jose , Beyene Yoseph , Montesinos-López Osval A. , Olsen Michael S. , Prasanna Boddupalli M.
Published: January 2021

Key message

Genome-wide association revealed that resistance toStriga hermonthicais influenced by multiple genomic regions with moderate effects. It is possible to increase genetic gains from selection for Striga resistance using genomic prediction.

Striga hermonthica(Del.) Benth., commonly known as the purple witchweed or giant witchweed, is a serious problem for maize-dependent smallholder farmers in sub-Saharan Africa. Breeding forStrigaresistance in maize is complicated due to limited genetic variation, complexity of resistance and challenges with phenotyping. This study was conducted to (i) evaluate a set of diverse tropical maize lines for their responses toStrigaunder artificial infestation in three environments in Kenya; (ii) detect quantitative trait loci associated withStrigaresistance through genome-wide association study (GWAS); and (iii) evaluate the effectiveness of genomic prediction (GP) ofStriga-related traits. An association mapping panel of 380 inbred lines was evaluated in three environments under artificialStrigainfestation in replicated trials and genotyped with 278,810 single-nucleotide polymorphism (SNP) markers. Genotypic and genotype x environment variations were significant for measured traits associated withStrigaresistance. Heritability estimates were moderate (0.42) to high (0.92) for measured traits. GWAS revealed 57 SNPs significantly associated withStrigaresistance indicator traits and grain yield (GY) under artificialStrigainfestation with low to moderate effect. A set of 32 candidate genes physically near the significant SNPs with roles in plant defense against biotic stresses were identified. GP with different cross-validations revealed that prediction of performance of lines in new environments is better than prediction of performance of new lines for all traits. Predictions across environments revealed high accuracy for all the traits, while inclusion of GWAS-detected SNPs led to slight increase in the accuracy. The item-based collaborative filtering approach that incorporates related traits evaluated in different environments to predict GY andStriga-related traits outperformed GP forStrigaresistance indicator traits. The results demonstrated the polygenic nature of resistance toS. hermonthica, and that implementation of GP inStrigaresistance breeding could potentially aid in increasing genetic gain for this important trait.
Does exposure to startle impact voluntary reaching movements in individuals with severe-to-moderate stroke?
Authors: Rahimi Marziye , Swann Zoe , Honeycutt Claire F.
Published: January 2021

When movements of individuals with stroke (iwS) are elicited by startling acoustic stimulus (SAS), reaching movements are faster, further, and directed away from the body. However, these startle-evoked movements also elicit task-inappropriate flexor activity, raising concerns that chronic exposure to startle might also induce heightened flexor activity during voluntarily elicited movement. The objective of this study is to evaluate the impact of startle exposure on voluntary movements during point-to-point reaching in individuals with moderate and severe stroke. We hypothesize that startle exposure will increase task-inappropriate activity in flexor muscles, which will be associated with worse voluntarily initiated reaching performance (e.g. decreased distance, displacement, and final accuracy). Eleven individuals with moderate-to-severe stroke (UEFM = 8–41/66 and MAS = 0–4/4) performed voluntary point-to-point reaching with 1/3 of trials elicited by an SAS. We used electromyography to measure activity in brachioradialis (BR), biceps (BIC), triceps lateral head (TRI), pectoralis (PEC), anterior deltoid (AD), and posterior deltoid (PD). Conversely to our hypothesis, exposure to startle did not increase abnormal flexion but rather antagonist activity in the elbow flexors and shoulder horizontal adductors decreased, suggesting that abnormal flexor/extensor co-contraction was reduced. This reduction of flexion led to increased reaching distance (18.2% farther), movement onset (8.6% faster), and final accuracy (16.1% more accurate) by the end of the session. This study offers the first evidence that exposure to startle in iwS does not negatively impact voluntary movement; moreover, exposure may improve volitionally activated reaching movements by decreasing abnormal flexion activity.
Salt-Laden Winter Runoff and Freshwater Mussels; Assessing the Effect on Early Life Stages in the Laboratory and Wild Mussel Populations in Receiving Waters
Authors: Gillis Patricia L. , Salerno Joseph , McKay Vicki L. , Bennett C. James , Lemon Karen L. K. , Rochfort Quintin J. , Prosser Ryan S.
Published: January 2021

The widespread use of road salt for winter road maintenance has led to an increase in the salinity of surface water in many seasonally cold areas. Freshwater mussels have a heightened sensitivity to salt, which is a concern, because many Canadian mussel species at risk have ranges limited to southern Ontario, Canada’s most road-dense region. This study examined the effect of winter road runoff on freshwater mussels. The impact of two bridges that span mussel habitat in the Thames River watershed (Ontario, Canada), the second most species-rich watershed for mussels in Canada, were studied. During a winter melt event, bridge runoff, as well as creek surface water surrounding the bridges were collected. Chloride concentrations in samples from bridge deck and tile drains varied (99–8250 mg/L). In general, survival of Lampsilis fasciola glochidia exposed to those samples reflected chloride levels (e.g. 84% at 99 mg/L; 0% at 8250 mg/L), although potassium (60 mg/L) may have at least contributed to toxicity in one sample. Serial dilution exposures with the two most toxic runoff samples revealed 48-h glochidia EC50s of 44% (McGregor Creek Tile Drain) and 26% (Baptiste Creek Deck Drain). During the melt event, the chloride concentrations in creek surface waters downstream of the bridges ranged from 69 to 179 mg Cl−/L; effects on glochidia (viability 77–91%) exposed to those waters was minimal. There were no live mussels surrounding one bridge (Baptiste Creek), likely due to poor habitat. At the other targeted bridge (McGregor Creek), fewer mussels were found close (< 100 m up- or downstream) to the bridge than further (> 200 m) away. However, other contributing factors, including agriculture, were present at both study areas.
APX005M, a CD40 agonist antibody with unique epitope specificity and Fc receptor binding profile for optimal therapeutic application
Authors: Filbert Erin L. , Björck Pia K. , Srivastava Minu K. , Bahjat Frances R. , Yang Xiaodong
Published: January 2021

Targeting CD40 with agonist antibodies is a promising approach to cancer immunotherapy. CD40 acts as a master regulator of immunity by mobilizing multiple arms of the immune system to initiate highly effective CD8 + T-cell-mediated responses against foreign pathogens and tumors. The clinical development of CD40 agonist antibodies requires careful optimization of the antibody to maximize therapeutic efficacy while minimizing adverse effects. Both epitope specificity and isotype are critical for CD40 agonist antibody mechanism of action and potency. We developed a novel antibody, APX005M, which binds with high affinity to the CD40 ligand-binding site on CD40 and is optimized for selective interaction with Fcγ receptors to enhance agonistic potency while limiting less desirable Fc-effector functions like antibody-dependent cellular cytotoxicity of CD40-expressing immune cells. APX005M is a highly potent inducer of innate and adaptive immune effector responses and represents a promising CD40 agonist antibody for induction of an effective anti-tumor immune response with a favorable safety profile.
Identification of Glisson's Capsule Invasion During Hepatectomy for Colorectal Liver Metastasis by Contrast‐Enhanced Ultrasonography Using Perflubutane
Authors: Hiroyoshi Junko , Ishizawa Takeaki , Abe Hiroyuki , Arita Junichi , Akamatsu Nobuhisa , Kaneko Junichi , Ushiku Tetsuo , Hasegawa Kiyoshi
Published: January 2021

Background

Glisson invasion by CLM is associated with a risk of margin‐positive resection, leading to poor long‐term outcomes after hepatectomy. This study was performed to evaluate the efficacy of intraoperative ultrasonography (IOUS) for the diagnosis of Glisson's capsule invasion by colorectal liver metastasis (CLM).

Methods

This prospective study involved 50 consecutive patients undergoing hepatectomy for CLM. Preoperatively, all patients had undergone gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid‐enhanced magnetic resonance imaging (EOB‐MRI). During hepatectomy, a contrast agent (perflubutane) was intravenously injected and Glisson invasion was estimated based on three characteristic findings: a tumor thrombus, peripheral dilatation, and border irregularity/caliber change. The diagnostic abilities of the preoperative and intraoperative imaging studies were evaluated based on pathological examinations of resected specimens.

Results

Among 187 CLMs resected, pathological examinations proved Glisson invasion in 24 tumors (13%). IOUS revealed a tumor thrombus in 3 tumors (1.6%), peripheral dilatation in 4 (2.1%), and border irregularity and/or caliber change in 24 (12.8%). The sensitivity and specificity of IOUS with any of the above three findings for diagnosis of Glisson invasion was 79% and 96%, respectively, while preoperative EOB‐MRI detected Glisson invasion in only four tumors (sensitivity/specificity, 17%/100%). The cutoff value of caliber change for diagnosis of Glisson invasion was set at 140% by receiver operating characteristic analysis. The R0 resection rates were not significantly different between patients with (82%) and without (85%) Glisson invasion.

Conclusions

Identification of characteristic findings (tumor thrombus, peripheral dilatation, and border irregularity/caliber change) by contrast‐enhanced IOUS is useful for the prediction of Glisson invasion by CLM.
If in Doubt Don't Act Out! Exploring Behaviours in Clinical Decision Making by General Surgeons Towards Surgical Procedures
Authors: Whelehan Dale F. , Conlon Kevin C. , Ridgway Paul F.
Published: January 2021

Background

Clinical decision‐making (CDM) plays an integral role to surgeons work and has ramifications for patient outcomes and experience. The factors influencing a surgeons decision‐making and the utility of cognitive decisional short cuts used in CDM known as ‘heuristics’ remains unknown. The aim of this paper is to explore how general surgeons make decisions in high‐stake biliary tract clinical scenarios.

Methods

This was a cross sectional survey comprising of two sections—a ‘demographics section’ and a ‘clinical vignettes section’. Participants were recruited by an email distributed by the Royal College of Surgeons in Ireland. Non‐parametric testing examined relationships and content analysis was applied for clinical reasoning.

Results

73 participants or 37.6% of the overall population completed the survey. 71.4% of these were male. Most (50%) were higher trainees with moderate levels of overall reflective practice in decision‐making. A majority of participants chose conservatively in high‐stake biliary tract clinical cases with disease factors (43.5%) weighted highest, followed by personal factors (41.1%) and patient factors (15.4%) in clinical reasoning. The presence of a ‘hook’ associated with commonly used heuristics did not significantly change decision‐making behaviour.

Conclusion

In high‐stake scenarios, surgeons make conservative clinical decisions, predominantly dominated by disease and personal justifications. The utility of heuristics in lower‐stake scenarios should be explored regarding clinical decision‐making rationale and outcomes. Practitioners should consider use of patient factors in high‐stake decisions to enable shared decision‐making when appropriate which can reduce post‐decisional regret and support the vision of patient‐centred care.
Enhanced Training Benefits of Video Recording Surgery With Automated Hand Motion Analysis
Authors: Mackenzie Colin F. , Yang Shiming , Garofalo Evan , Hu Peter Fu‐Ming , Watts Darcy , Patel Rajan , Puche Adam , Hagegeorge George , Shalin Valerie , Pugh Kristy , Granite Guinevere , Stansbury Lynn G. , Shackelford Stacy , Tisherman Samuel
Published: January 2021

Background

Hand motion analysis by video recording during surgery has potential for evaluation of surgical performance. The aim was to identify how technical skill during open surgery can be measured unobtrusively by video recording during a surgical procedure. We hypothesized that procedural‐step timing, hand movements, instrument use and Shannon entropy differ with expertise and training and are concordant with a performance‐based validated individual procedure score.

Methods

Surgeon and non‐surgeon participants with varying training and levels of expertise were video recorded performing axillary artery exposure and control (AA) on un‐preserved cadavers. Color‐coded gloves permitted motion‐tracking and automated extraction of entropy data from recordings. Timing and instrument‐use metrics were obtained through observational video reviews. Shannon entropy measured speed, acceleration and direction by computer‐vision algorithms. Findings were compared with individual procedure score for AA performance

Results

Experts had lowest entropy values, idle time, active time and shorter time to divide pectoralis minor, using fewer instruments. Residents improved with training, without reaching expert levels, and showed deterioration 12–18 months later. Individual procedure scores mirrored these results. Non‐surgeons differed substantially.

Conclusions

Hand motion entropy and timing metrics discriminate levels of surgical skill and training, and these findings are congruent with individual procedure score evaluations. These measures can be collected using consumer‐level cameras and analyzed automatically with free software. Hand motion with video timing data may have widespread application to evaluate resident performance and can contribute to the range of evaluation and testing modalities available to educators, training course designers and surgical quality assurance programs.
The leading modes of NH extratropical tropopause variability and their connection with stratosphere-troposphere variability
Authors: Kim Jinju , Kim Kwang-Yul
Published: January 2021

The leading modes of Northern Hemisphere tropopause variability for November–April (1979/1980–2018/2019) and the associated stratosphere-troposphere variability were analyzed based on the NCEP and ERA interim reanalysis products. For this, cyclostationary empirical orthogonal function technique is employed. The first two modes feature the intraseasonal evolution of tropopause pressure anomalies over the Arctic, which respond directly to stratospheric temperature fluctuations in association with stratospheric polar vortex variations. These two modes reflect the link between stratospheric polar vortex strength and high-latitude tropospheric circulation. The first mode represents a single-phase fluctuation of the stratospheric polar vortex from winter to early spring. The second mode describes a two-phase fluctuation of the stratospheric vortex with opposite signs in winter and in spring. Tropopause pressure anomalies near the mid-latitude tropospheric jet regions exhibit significant zonal variation. In the first mode, in particular, these mid-latitude tropopause anomalies are linked to asymmetric jet variations in the Atlantic and the Pacific regions. In regard to the Northern Annular mode, distinct vertical evolution structures of the two modes are practically related to the varying evolutionary structure of extreme vortex events with relatively long persistence.
Is a diluted seawater-based solution safe and effective on human nasal epithelium?
Authors: Huang Song , Constant Samuel , De Servi Barbara , Meloni Marisa , Saaid Amina , Culig Josip , Bertini Marco
Published: January 2021

Purpose

Nasal irrigation is an effective method for alleviating several nasal symptoms and regular seawater-based nasal irrigation is useful for maintaining nasal hygiene which is essential for appropriate functioning of the nose and for preventing airborne particles including some pollutants, pathogens, and allergens from moving further in the respiratory system. However, safety studies on seawater-based nasal irrigation are scarce. In this study, the safety and efficacy of a diluted isotonic seawater solution (Stérimar Nasal Hygiene, SNH) in maintaining nasal homeostasis were evaluated in vitro.

Methods

Safety was assessed by measuring tissue integrity via transepithelial electrical resistance (TEER). Efficacy was measured by mucociliary clearance (MCC), mucin secretion, and tissue re-epithelization (wound repair) assays. All assays were performed using a 3D reconstituted human nasal epithelium model.

Results

In SNH-treated tissues, TEER values were statistically significantly lower than the untreated tissues; however, the values were above the tissue integrity limit. SNH treatment significantly increased MCC (88 vs. 36 µm/s, p < 0.001) and mucin secretion (1717 vs. 1280 µg/ml, p < 0.001) as compared to untreated cultures. Faster wound closure profile was noted upon pre-SNH treatment as compared to classical isotonic saline solution pre-treatment (90.5 vs. 50.7% wound closure 22 h after wound generation).

Conclusion

SNH did not compromise the integrity of the nasal epithelium in vitro. Furthermore, SNH was effective for removal of foreign particles through MCC increase and for enhancing wound repair on nasal mucosa.
The usefulness of a trauma probability of survival model for forensic life-threatening danger assessments
Authors: Jakobsen Lykke Schrøder , Lynnerup Niels , Steinmetz Jacob , Banner Jytte
Published: January 2021

Clinical forensic medical examinations constitute an increasing proportion of our institution’s tasks, and, concomitantly, the authorities are now requesting forensic life-threatening danger assessments based on our examinations. The aim of this retrospective study was to assess if a probability of survival (PS) trauma score could be useful for these forensic life-threatening danger assessments and to identify a cut-off PS score as a supporting tool for the forensic practice of assessing life-threatening danger. We compared a forensic database and a trauma database and identified 161 individuals (aged 15 years or older) who had both a forensic life-threatening danger assessment and a PS score. The life-threatening danger assessments comprised the following statements: was not in life-threatening danger (NLD); could have been in life-threatening danger (CLD); or was in life-threatening danger (LD). The inclusion period was 2012–2016. A statistically significant difference was found in the PS scores between NLD, CLD and LD (chi-square test: p < 0.0001). The usefulness of the PS score for categorizing life-threatening danger assessments was determined by a receiver-operator characteristic (ROC) curve. The area under the curve was 0.76 (95% CI, 0.69 to 0.84) and the ROC curve revealed that a cut-off PS score of 95.8 would appropriately identify LD. Therefore, a PS score below 95.8 would indicate life-threatening danger. We propose a further exploration of how the evidence-based PS score, including a cut-off value, might be implemented in clinical forensic medical statements to add to the scientific strength of these statements.
Involuntary sustained firing of plantar flexor motor neurones: effect of electrical stimulation parameters during tendon vibration
Authors: Mesquita Ricardo N. O. , Taylor Janet L. , Kirk Benjamin , Blazevich Anthony J.
Published: January 2021

Purpose

Simultaneous application of tendon vibration and neuromuscular electrical stimulation (NMES) induces an involuntary sustained torque. We examined the effect of different NMES parameters (intensity, pattern of stimulation and pulse width) on the magnitude of the evoked involuntary torque.

Methods

Plantar flexor torque was recorded during 33-s Achilles tendon vibration with simultaneous 20-Hz NMES bouts on triceps surae (n = 20; 13 women). Intensity was set to elicit 10, 20 or 30% of maximal voluntary contraction torque (MVC), pulse width was narrow (0.2 ms) or wide (1 ms), and the stimulus pattern varied (5 × 2-s or 10 × 1-s). Up to 12 different trials were performed in a randomized order, and then repeated in those who produced a sustained involuntary torque after the cessation of vibration.

Results

Six of 7 men and 5 of 13 women produced a post-vibration sustained torque. Eight of 20 participants did not complete the 30% trials, as they were perceived as painful. Torque during vibration at the end of NMES and the increase in torque throughout the trial were significantly higher in 20 than 10% trials (n = 11; 9.7 ± 9.0 vs 7.1 ± 6.1% MVC and 4.3 ± 4.5 vs 3.6 ± 3.5% MVC, respectively). Post-vibration sustained torque was higher in wide pulse-width trials (5.4 ± 5.9 vs 4.1 ± 4.3% MVC). Measures of involuntary torque were not different between 20 and 30% trials (n = 8).

Conclusion

Bouts of 5 × 2-s NMES with wide pulse width eliciting 20% MVC provides the most robust responses and could be used to maximise the production of involuntary torque in triceps surae.
Significance of indeterminate pulmonary nodules in resectable pancreatic adenocarcinoma—a review
Authors: Kuan Li Lian , Dennison Ashley R. , Garcea Giuseppe
Published: January 2021

Background

The clinical significance of indeterminate pulmonary nodules (IPN) in patients with resectable pancreatic adenocarcinoma (PDAC) is unknown. The rate of detection on IPN has risen due to enhanced staging investigations to determine resectability. IPNs detected on preoperative imaging represent a clinical dilemma and complicate decision-making. Currently, there are no recommendations on the management of IPN. This review provides a comprehensive overview of the current knowledge on the natural history of IPN detected among patients with resectable PDAC.

Methods

A systematic review based on a search in Medline and Embase databases was performed. All clinical studies evaluating the significance of IPN in patients with resectable PDAC were included. PRISMA guidelines were followed.

Results

Five studies met the inclusion criteria. The total patient population was 761. The prevalence of IPN reported ranged from 18 to 71%. The median follow-up duration was 17 months. The median overall survival was 19 months. Patients with pre-operative IPN which subsequently progressed to clinically recognizable pulmonary metastases, ranged from 1.5 to 16%. Four studies found that there was no significant difference in median overall survival in patients with or without IPNs.

Conclusion

This is a first review on the significance of IPN in patients with resectable PDAC. The preoperative presence of IPN does not demonstrate an association with overall survival after surgery. The identification of IPN is a significant finding however it should not preclude patients with resectable PDAC from undergoing curative resection.
Cabozantinib in Japanese patients with advanced hepatocellular carcinoma: a phase 2 multicenter study
Authors: Kudo Masatoshi , Tsuchiya Kaoru , Kato Naoya , Hagihara Atsushi , Numata Kazushi , Aikata Hiroshi , Inaba Yoshitaka , Kondo Shunsuke , Motomura Kenta , Furuse Junji , Ikeda Masafumi , Morimoto Manabu , Achira Meguru , Kuroda Shingo , Kimura Akiko
Published: January 2021

Background

To evaluate the efficacy and safety of cabozantinib in Japanese patients with advanced hepatocellular carcinoma (HCC) who had progressed following one or two lines of systemic therapy including sorafenib. An exploratory evaluation in sorafenib-naïve patients was performed.

Methods

In this open-label, single-arm, phase 2 trial, patients received oral cabozantinib 60 mg once daily. The primary endpoint was progression-free survival (PFS) rate at Week 24. Secondary endpoints included PFS, overall survival (OS), objective response rate (ORR, best response of complete/partial response), disease control rate (DCR, objective response or stable disease) and safety.

Results

Thirty-four patients received cabozantinib across 17 centers (prior sorafenib cohort, n = 20; sorafenib-naïve cohort, n = 14). PFS rate at 24 weeks was 59.8% [90% confidence interval (CI) 36.1–77.2%] in the prior sorafenib cohort, 16.7% (90% CI 4.0–36.8%) in the sorafenib-naïve cohort and 40.1% (90% CI 24.8–55.0%) overall. Median PFS was 7.4 months for the prior sorafenib cohort, 3.6 months for the sorafenib-naïve cohort, and 5.6 months overall. OS rate at 6 months was 100.0%, 78.6% and 91.1%, respectively; DCR was 85.0%, 64.3% and 76.5%, respectively. The ORR was 0.0% for both cohorts. All patients required dose modifications due to adverse events, the most common of these were palmar–plantar erythrodysesthesia syndrome and diarrhea. Three patients (8.8%) discontinued due to adverse events other than disease progression.

Conclusions

Cabozantinib 60 mg/day has a favorable benefit/risk profile for Japanese patients with advanced HCC who have previously received one or two lines of systemic anticancer therapy including sorafenib. (Clinical trial registration: NCT03586973)
Performance and Reuse of Steel Shot in Abrasive Waterjet Cutting of Granite
Authors: Cha Yohan , Oh Tae-Min , Joo Gun-Wook , Cho Gye-Chun
Published: January 2021

Steel shots are suitable for abrasive waterjet rock cutting and recycling because of the high hardness and magnetic properties of steel. This study evaluated the rock-cutting performance and recycling characteristics of steel shot waterjet. The rock-cutting responses of steel shot and garnet were compared at the same waterjet conditions. The used steel shot was collected and the particle-size changes were evaluated before reuse, and its cutting performance was re-evaluated. Overall, the steel shot waterjet yielded improvements in performance in the range of 30–50% compared with the garnet waterjet. Moreover, the recycled steel shot yielded a 50% reduction in cutting performance. Rust was observed on the surface of the used steel shot, the used steel shots were partially destroyed, and the debris on the abrasive surface needed to be removed by drying. The reusable steel shot left on the 80th sieve converged to 60% in each recycling run. The results of this study can be used to reduce the cost of abrasive waterjet and industrial waste.