bluuebunny/crossref_metadata_2025 huggingface dataset:
Emergency admissions of ambulatory care sensitive conditions at a Japanese local hospital: An observational study
Authors: Shinotsuka Manami , Matsumura Shin , Okada Tadao
Published: June 2020

Background

Emergency admissions of ambulatory care sensitive conditions (ACSCs) are a key marker of quality of primary care and are used nationwide in some countries including the UK and Australia. There are still little data on ACSCs available in Japan. This study aimed to provide the descriptive data of the current state of ACSCs at a local hospital in Japan.

Methods

This is an observational study of retrospective chart review. The study setting is Funabashi Futawa Hospital (FFH), an acute care private hospital in Funabashi City, Japan. We analyzed the shares of admissions of ACSCs out of all admissions at FFH from April 2014 to March 2015.

Results

5380 charts were reviewed. Emergency admissions were 3275 cases (61%) of all admissions. Emergency admissions for ACSCs accounted for 946 cases (28.9%) of all emergency admissions. Chronic ACSC is the most common subcategory. Urinary tract infection accounted most for admissions of acute ACSCs (138 cases, 4.2% of all emergency admissions). Asthma accounted most for admissions of chronic ACSCs (139 cases, 4.2%). Pneumonia accounted most for admissions of vaccine‐preventable ACSCs (99 cases, 3.0%).

Conclusions

This is one of the first reports describing ACSCs in Japan. Most common reasons for ACSCs were similar to the previous data from the UK, except COPD ranked lower and asthma ranked higher, respectively. Comparison among different facilities (horizontal) and over time in the same institution (longitudinal), as well as analyzing relationships between other markers of primary care quality and ACSCs, will be necessary in the future.
Synthesis of isoniazid‐1,2,3‐triazole conjugates: Antitubercular, antimicrobial evaluation and molecular docking study
Authors: Badar Adinath D. , Sulakhe Shubham M. , Muluk Mahesh B. , Rehman Naziya N. M. A. , Dixit Prashant P. , Choudhari Prafulla B. , Rekha Estharla Madhu , Sriram Dharmarajan , Haval Kishan P.
Published: June 2020

In the present study, a series of new isoniazid‐1,2,3‐triazole conjugates (5a‐k) was synthesized via click chemistry approach. The newly synthesized compounds were assessed for their in vitro antitubercular and antimicrobial activities. The compound 5g has displayed potent antitubercular activity against Mycobacterium tuberculosis H37Rv (Mtb) with MIC value 1.56 μg/mL. The active compounds were screened for their cytotoxicity profile by MTT assay against RAW 264.7 cell line. The four compounds have shown good in vitro antimicrobial activities against both antibacterial and antifungal pathogens. A molecular docking study was accomplished to identify the probable mode of action of synthesized derivatives. These compounds have shown excellent binding affinity toward Enoyl‐acp reductase (INHA) and DNA gyrase.
Effect of matrices and additives on phosphorylated and ketodeoxyoctonic acid lipids A analysis by matrix‐assisted laser desorption ionization‐mass spectrometry
Authors: Jabbar Siddiqui Amna , Le Sénéchal Caroline , Vilain Sébastien , Buré Corinne
Published: June 2020

Lipid A is a major compound of the outer membrane of gram‐negative bacteria and is a key factor of bacterial virulence. As lipid A's structure differs among bacterial species and varies between strains of the same species, knowing its modifications is essential to understand its implications in the infectious process. To analyze these lipids, matrix‐assisted laser desorption ionization‐mass spectrometry (MALDI‐MS) is a well‐suited method that is fast and efficient. However, there are limitations with the matrix and additives used, such as the suppression of signal or prompt fragmentations that could give a false overview of lipid A composition in biological samples. For a comprehensive analysis of the entire lipid A species present in a sample, we tested 16 matrices and 11 additives on two commercial lipids A. The first commercial one contains single phosphorylation group, and the second contains two phosphorylation and two ketodeoxyoctonic acid (KDO) groups. The lipid A containing KDO groups was essentially detected by the 3‐hydroxypicolinic acid (3‐HPA) matrix, whereas the monophosphorylated lipid A could be detected by 13 matrices out of the 16. We also demonstrated that the signal of diphosphorylated lipid A can be enhanced with the use of additives in the matrix. Our study indicated that the best conditions to obtain a clear signal of both lipids A without prompt fragmentation was the use of 3‐HPA with 10mM trifluoroacetic acid (TFA).
Therapeutic drug monitoring of valproic acid using a dried plasma spot sampling device
Authors: Li Yanyan , Jiang Yi , Cao Haiwei , Lin Hua , Ren Wenbo , Huang Jing , Zhang Jie
Published: June 2020

Valproic acid (VPA) dosing needs to be individualized for epilepsy patients through therapeutic drug monitoring (TDM). The patients must show up in the clinic at the therapeutic window time to venipuncture sample. Dried plasma spot (DPS) sampling is an alternative way to replace conventional venipuncture sampling. The aim of this study was to develop and validate a DPS‐based liquid chromatography–tandem mass spectrometry (LC–MS/MS) method to monitor VPA in a routine clinical laboratory setting. We compare the DPS with the wet plasma method of clinical samples by LC–MS/MS. The method was linear over the dynamic range of 10–200 μg/ml (covering entire therapeutic range) with a correlation coefficient r2 ≥ 0.995. Both the DPS and wet plasma methods were fully validated for the accuracy, precision, recovery, and matrix effect. The analyte stability was examined under conditions mimicking the sample storage, transport, and analysis procedures. A clinical study with epilepsy patients receiving VPA (n = 35) showed that, after correction for hematocrit (HCT), plasma concentrations can be successfully calculated from the DPS quantification results. Passing–Bablok regression coefficients showed no proportional bias between estimated and measured plasma concentrations. Similar agreement was found by Bland–Altman plots. The dried sample could be mailed to the clinical lab to test by regular mail service. So DPS can be used for drug monitoring with self‐sampling strategy at the patient's convenient time and place specially for ambulatory patients not attending a clinic.
Preparation and Properties of UCST‐Type Thermoresponsive Polypeptide Bearing Amide Pendants
Authors: Huang Linjie , Sun Liwei , Zhou Congping , Ling Ying , Lu Hua , Luan Shifang , Tang Haoyu
Published: June 2020

Thermoresponsive polypeptides bearing amide pendants with an upper critical solution temperature (UCST) under physiologically relevant solution conditions are developed. A series of poly(γ‐propanyl‐l‐glutamate)s bearing amide pendants (PPLGn‐Am) with different molecular weight (or degree of polymerization, DP) is prepared by copper mediated 1,3‐dipolar cycloaddition. While fourier transform infra‐red and CD analysis reveal random coil conformation of the PPLGn‐Am in the solid‐state and in aqueous solutions, respectively, PPLGn‐Am shows reversible UCST‐type phase behaviors in deionized water (DI) water and phosphate‐buffered saline. Variable temperature UV–vis spectroscopy indicates that the UCST‐type cloud point temperature (Tcp) in the range of 25–75 °C can be readily tuned by molecular weight (or DP), polymer concentration, and incorporation of hydrophobic (i.e., n‐hexyl) pendants. Moreover, PPLGn‐Am is readily degraded by proteinase K within 48 h. The results indicate that UCST‐type thermoresponsive and biodegradable polypeptides in aqueous solutions can be constructed by conjugation of amide pendants which shall provide guidance for future UCST polymer designs.
Dynamic Covalent Chemistry Enables Reconfigurable All‐Polysaccharide Nanogels
Authors: Abdi Fatma , Michel Raphaël , Poirot Robin , Dakir Malika , Sancey Lucie , Ravaine Valérie , Auzély‐Velty Rachel
Published: June 2020

Dynamic covalent bonds are established upon molecular recognition of sugar derivatives by boronic acid molecules. These reversible links can be used in a cross‐linking method to fabricate polymer‐based responsive nanosystems. Herein, the design of the first dynamic nanogels made entirely of polysaccharides (PS) is reported. Based on PS chains alternately modified with phenyl boronic acid groups and sugar moieties, these colloids self‐assemble in physiological conditions and combine the biocompatible nature of their PS backbone with the reconfiguration capacities of their cross‐linking chemistry. These dynamic nanogels are easily prepared, stable for a long time, pH responsive, and efficiently internalized by cancer cells.
Enhancing anticancer activity of checkpoint immunotherapy by targeting RAS
Authors: Ward Antonio B. , Keeton Adam B. , Chen Xi , Mattox Tyler E. , Coley Alex B. , Maxuitenko Yulia Y. , Buchsbaum Donald J. , Randall Troy D. , Zhou Gang , Piazza Gary A.
Published: June 2020

Approximately 30% of human cancers harbor a gain‐in‐function mutation in the RAS gene, resulting in constitutive activation of the RAS protein to stimulate downstream signaling, including the RAS‐mitogen activated protein kinase pathway that drives cancer cells to proliferate and metastasize. RAS‐driven oncogenesis also promotes immune evasion by increasing the expression of programmed cell death ligand‐1, reducing the expression of major histocompatibility complex molecules that present antigens to T‐lymphocytes and altering the expression of cytokines that promote the differentiation and accumulation of immune suppressive cell types such as myeloid‐derived suppressor cells, regulatory T‐cells, and cancer‐associated fibroblasts. Together, these changes lead to an immune suppressive tumor microenvironment that impedes T‐cell activation and infiltration and promotes the outgrowth and metastasis of tumor cells. As a result, despite the growing success of checkpoint immunotherapy, many patients with RAS‐driven tumors experience resistance to therapy and poor clinical outcomes. Therefore, RAS inhibitors in development have the potential to weaken cancer cell immune evasion and enhance the antitumor immune response to improve survival of patients with RAS‐driven cancers. This review highlights the potential of RAS inhibitors to enhance or broaden the anticancer activity of currently available checkpoint immunotherapy.
A 17q24.3 duplication identified in a large Chinese family with brachydactyly‐anonychia
Authors: Liu Mohan , Zhang Xueguang , Liu Hongqian , Shen Ying
Published: June 2020

Background

Brachydactyly (BD) is a rare autosomal dominant inherited disease characterized by shortness of the fingers and/or toes, which has been classified into the subtypes A–E. However, the exact cause and mechanism of BD remain to be illuminated. Here, we aim to reveal the clinical and genetic characteristics of a subtype of BD, brachydactyly‐anonychia.

Methods

In this study, a large Chinese family with three members affected by brachydactyly‐anonychia was investigated. Both whole‐exome sequencing and microarray‐based comparative genomic hybridization (CGH) were performed on this family and the results of copy number variation (CNV) were verified by quantitative real‐time PCR (qPCR).

Results

All the affected individuals showed short fingers and toes as well as missing nails; and the absence of middle phalanges in figure II‐V of the upper and lower extremities was observed by X‐ray examination. A duplication involving in the region of 17q24.3 was detected by CGH. The results of qPCR also represented this duplication in 17q24.3 in all the patients.

Conclusion

In summary, our findings suggest that 17q24.3 duplication is the genetic cause of brachydactyly‐anonychia in this family, which support the prior report that brachydactyly‐anonychia is associated with 17q24.3 duplication, and further indicates the pathogenic correlation between BD and CNVs.
Microbial Products and Metabolites Contributing to Alcohol‐Related Liver Disease
Authors: Gao Bei , Emami Atoosa , Nath Shilpa , Schnabl Bernd
Published: June 2020

As a serious public health concern, alcohol‐related liver disease is associated with dysregulations in the intestinal barrier function and the gut microbiota. The liver and gut communicate via the gut–liver axis, through which microbial products and metabolites translocate to the liver. Here, the current knowledge of various microbial products and metabolites which contribute to the alcohol‐related liver diseases, including bile acids, indole‐3‐acetic acid, butyrate, long‐chain fatty acids, endotoxin, cytolysin, β‐glucan, and candidalysin is reviewed. Some of these might serve as therapeutic targets for alcohol‐related liver disease.
Automatic arterial input function selection in CT and MR perfusion datasets using deep convolutional neural networks
Authors: Winder Anthony , d’Esterre Christopher D. , Menon Bijoy K. , Fiehler Jens , Forkert Nils D.
Published: June 2020

Purpose

The computation of perfusion parameter images requires knowledge of the arterial blood flow in the form of an arterial input function (AIF). This work proposes a novel method to automatically identify AIFs in computed tomography perfusion (CTP) and dynamic susceptibility contrast perfusion‐weighted MRI (PWI) datasets using a deep convolutional neural network (CNN).

Methods

One‐hundred CTP and 100 PWI datasets of acute ischemic stroke patients were available for model development and evaluation. For each modality, 50 datasets were used for CNN training and 20 for validation using manually selected AIFs and non‐arterial tissue concentration time curves. Model evaluation was performed using the remaining 30 independent validation datasets from each modality with manual AIF selections provided by two experts as ground truth. Additionally, AIFs were also extracted using an established automatic shape‐based algorithm for comparison purposes. The extracted AIFs were compared using normalized cross‐correlation and shape features as well as using the Dice similarity metric and volume of the corresponding hypoperfusion (Tmax > 6 s) lesions.

Results

The cross‐correlation values comparing the manual AIFs and those extracted by the proposed CNN method were significantly greater than those comparing the manual AIFs to the shape‐based comparison method. Likewise, hypoperfusion lesions generated using the manually selected AIFs and CNN‐based AIFs showed higher Dice values compared to hypoperfusion lesions generated using the comparison AIF extraction method. Shape features for AIFs generated by the proposed method did not differ significantly from the manual AIFs, with the exception that the CNN‐derived AIFs for the PWI datasets showed marginally greater peak heights.

Conclusion

Deep convolutional neural network models are viable for the automatic extraction of the AIF from CTP and PWI datasets.
Counselors network for intrusion detection
Authors: Quincozes Silvio E. , Raniery Carlos , Ceretta Nunes Raul , Albuquerque Célio , Passos Diego , Mossé Daniel
Published: June 2020

Intrusion detection systems (IDSs) are a fundamental component of defense solutions. In particular, IDSs aim to detect malicious activities on computer systems and networks by relying on data classification models built from a training dataset. However, classifiers' performance can vary for each attack pattern. A common technique to overcome this issue is to use ensemble methods, where multiple classifiers are employed and a final decision is taken combining their outputs. Despite the potential advantages of such an approach, its usefulness is limited in scenarios where (i) multiple expert classifiers present divergent results, (ii) all classifiers present poor results due to lack of representative features, or (iii) detectors have insufficient labeled signatures to train their classifiers for a specific attack pattern. In this work, we introduce the concept of a counselors network to deal with conflicts from different classifiers by exploiting the collaboration among IDSs that analyze multiple and heterogeneous data sources. Empirical results demonstrate the feasibility of the proposed architecture in improving the accuracy of the intrusion detection process.
Stabilization of linear time‐varying reduced‐order models: A feedback controller approach
Authors: Mojgani Rambod , Balajewicz Maciej
Published: June 2020

Many of the commonly used methods in model‐order reduction do not guarantee stability of the reduced‐order model. This article extends the eigenvalue reassignment method of stabilization of linear time‐invariant ROMs, to the more general case of linear time‐varying systems. Through a postprocessing step, the ROM is controlled to ensure the stability while enhancing/maintaining its accuracy using a constrained nonlinear lease‐square minimization problem. The controller and the input signals are defined at the algebraic level, using left and right singular vectors of the reduced system matrices. The choice provides a control on the upper bound of the growth of the energy of the reduced system. The optimization problem is applied to several time‐invariant, time‐periodic, and time‐varying problems, and the reproductive and predictive capabilities of the proposed method, with respect to novel inputs and the system parameters, are evaluated.
A robust scheme based on novel‐operational matrices for some classes of time‐fractional nonlinear problems arising in mechanics and mathematical physics
Authors: Usman Muhammad , Hamid Muhammad , Khalid Muhammad Saif Ullah , Haq Rizwan Ul , Liu Moubin
Published: June 2020

In this paper, we present a novel approach based on shifted Gegenbauer wavelets to attain approximate solutions of some classed of time‐fractional nonlinear problems. First, we present the approximation of a function of two variablesu(x,t) with help of shifted Gegenbauer wavelets and then some novel operational matrices are proposed with the help of piecewise functions to investigate the positive integer derivative (DxandDt), fractional‐order derivative (and), fractional‐order integration (and) and delay terms (and) of approximated functionu(x,t). In order to transform the discussed nonlinear problem into linear problem Picard iterative scheme has been adopt. The current scheme converts the discussed highly nonlinear time‐fractional problem into system of linear algebraic equation the help of developed operational matrices and Picard idea. Analysis on the error bound and convergence to authenticate the mathematical formulation of the computational algorithm. We solve various test problems, such as the van der Pol oscillator model, generalized Burger–Huxley, neutral delay parabolic differential equations, sine‐Gordon, parabolic integro‐differential equation and nonlinear Schrödinger equations to show the efficiency and accuracy of linearized shifted Gegenbauer wavelets method. A comprehensive comparative examination shows the credibility, accuracy, and reliability of the presently proposed computational approach. Also, this scheme can be extended conveniently to other multi‐dimensional physical problems of highly nonlinear fractional or variable order of complex nature.
Correlation between premonitory urges and tic symptoms in a Chinese population with tic disorders
Authors: Gu Yi , Li Ying , Cui Yonghua
Published: June 2020

Importance

Tics usually start around 4–6 years old and affect about 1% of school‐age children. Premonitory urges (PUs) are sensory phenomena that precede tics and are often described as unpleasant feelings. Recent evidence supports a relationship between PUs and tic severity, but reports are conflicting. In addition, there is no report of PUs in the Chinese population.

Objective

To investigate the correlation between PUs and tic symptoms in the Chinese population with tic disorders.

Methods

We recruited 252 Chinese individuals with chronic tic disorders (age 5–16 years). The Yale Global Tic Severity Scale (YGTSS) was used to assess tic symptoms, and the Premonitory Urge for Tics Scale (PUTS) was used to assess PUs. We calculated Spearman correlations between PUTS and YGTSS scores, and constructed a linear regression model to predict the tic symptom severity by PUs.

Results

There was a significant positive correlation between PU severity (PUTS scores) and motor tic severity, total tic severity, tic‐caused impairment (YGTSS scores) (P < 0.05). PU severity was a significant positive predictor of tic symptom severity (standardized beta coefficient = 0.174, t = 2.786, P = 0.006).

Interpretation

We provide evidence for a correlation between PUs and tic symptoms. PU severity predicts tic symptom severity. Further research on PUs is needed to clarify the shared brain mechanism with tics, and their role in tic expression. A suitable tool to assess PUs in younger children is also needed.
Short fixation with a 3‐rod technique for posterior hemivertebra resection in children younger than 5 years old
Authors: Guo Dong , Yao Ziming , Qi Xinyu , Li Chengxin , Zhang Xuejun
Published: June 2020

Importance

Congenital hemivertebra is commonly treated with posterior hemivertebra resection with bilateral transpedicular fixation. However, implant‐related complications are common in children younger than 5 years old who undergo this surgical procedure.

Objective

To present the preliminary clinical and radiological outcomes of children younger than 5 years old treated by posterior hemivertebra resection and 3‐rod fixation technique.

Methods

From January 2016 to December 2017, 14 consecutive patients of congenital scoliosis with 16 hemivertebrae were retrospectively reviewed, including 5 girls and 9 boys, aged between 25 and 55 months old (average, 37.6 months). All patients underwent posterior hemivertebra resection with short fixation with bilateral pedicle screws and a convex lamina hook. Surgical complications and corrective outcomes were assessed based on the clinical charts and spinal radiographs with a minimum 24‐month follow‐up.

Results

The mean Cobb angle of the main curve was 38.4° before surgery, 8.5° after surgery, and 8.7° at final follow‐up. In the compensatory cranial curve, the preoperative Cobb angle of 16.8° was corrected to 8.1° postoperatively and was 10.3° at final follow‐up. In the compensatory caudal curve, the preoperative Cobb angle of 15.9° improved to 5.3° postoperatively and was 7.8° at final follow‐up. The segmental kyphosis was corrected from 13.5° to 0.5° and was 1.1° at final follow‐up. There were no crankshaft phenomena, no proximal kyphosis, and no complications related to the instrumentation.

Interpretation

Posterior hemivertebra resection with instrumentation with bilateral pedicle screws and a convex lamina hook can achieve rigid fixation and deformity correction.
Development and validation of a bronchoscopically defined bronchitis scoring tool in children
Authors: Eg Kah Peng , Thomas Rahul J. , Masters Ian B. , McElrea Margaret S. , Marchant Julie M. , Chang Anne B.
Published: June 2020

Introduction/Aim

A validated tool for scoring bronchitis during flexible bronchoscopy (FB) is potentially useful for clinical practice and research. We aimed to develop a bronchoscopically defined bronchitis scoring system in children (BScore) based on our pilot study.

Methods

Children undergoing FB were prospectively enrolled. Their FB was digitally recorded and assessed (two clinicians blinded to each other and clinical history) for six features: secretion amount (six‐point scale), secretion color (BronkoTest, 0‐8), mucosal oedema (0‐3), ridging (0‐3), erythema (0‐3), and pallor (0‐3) based on pre‐determined criteria. We correlated (Spearman's rho) each feature with bronchoalveolar lavage (BAL) neutrophil percentage (neutrophil%). BScore was then derived using models with combinations of the six features that best related to airway BAL neutrophil%. The various models of BScore were plotted against BAL neutrophil% using receiver operating characteristic (ROC) curves.

Results

We analyzed 142 out of 150 children enrolled. Eight children were excluded for unavailability of BAL cytology or FB recordings. Chronic/recurrent cough was the commonest indication for FB (75%). The median age was 3 years (IQR, 1.5‐5.3 years). Secretion amount (r = 0.42) and color (r = 0.46), mucosal oedema (r = 0.42), and erythema (r = 0.30) significantly correlated with BAL neutrophil%, P < .0001. The highest area under ROC (aROC) was obtained by the addition of the scores of all features excluding pallor (aROC = 0.84; 95% CI, 0.76‐0.90) with airway neutrophilia (defined as BAL neutrophil% of >10%).

Conclusion

This prospective study has developed the first validated bronchitis scoring tool in children based on bronchoscopic visual inspection of airways. Further validation in other cohorts is however required.
Qualitative study of continuing nursing needs in patients with precision radiotherapy for nasopharyngeal carcinoma
Authors: Li Xiaodong , Lou Shuchang , Li Jun , Wang Yaxin , Xu Dejing
Published: June 2020

Objective

To explore the inner feelings and experiences of patients with precision radiotherapy for nasopharyngeal carcinoma after discharge on continue nursing needs, and to provide theoretical basis for the development of continuing nursing service for patients with nasopharyngeal carcinoma.

Method

By using the phenomenological analysis in qualitative research, face‐to‐face semistructured in‐depth interviews were conducted on 10 nasopharyngeal carcinoma (NPC) patients who received precision radiotherapy, and the data analysis was carried out by phenomenological analysis method, Colaizzi method.

Results

The continuing nursing needs of 10 NPC patients after discharge may be summarized under four main categories: expectation of disease prognosis and self‐care related knowledge, expectation of professional psychological counseling and mental care, strong willingness to seek social and family support, and expectation of accessible health services resources.

Conclusion

It is urgent to establish an effective continuous nursing service channel to meet the physical and mental needs of patients with nasopharyngeal carcinoma after discharge, and to continuously improve the life quality of patients with nasopharyngeal carcinoma.
Engaging undergraduate students in computational chemistry research: A tutorial for new assistant professors
Authors: Ball K. Aurelia , He Kedan , Hendrickson Heidi P.
Published: June 2020

In this article, we provide advice and insights, based on our own experiences, for computational chemists who are beginning new tenure‐track positions at primarily undergraduate institutions. Each of us followed different routes to obtain our tenure‐track positions, but we all experienced similar challenges when getting started in our new position. In this article, we discuss our approaches to seven areas that we all found important for engaging undergraduate students in our computational chemistry research, including setting up computational resources, recruiting research students, training research students, designing student projects, managing the lab, mentoring students, and student conference participation.
Undergraduate women empowering women in computational chemistry: Three perspectives
Authors: Evans Rebecca , Perchik Madison , Magee Caroline , Cafiero Mauricio
Published: June 2020

The undergraduate computational chemistry research group headed by Mauricio Cafiero at Rhodes College has a history of including, promoting, and supporting women in this predominantly male field. Alums of this research group from 2004 to 2019 include nine M.Ds, two science researchers, two Ph.D.s, one secondary teacher, two pharmacists, a physical therapist, two nurses, six current medical school students, and five current science graduate students. They have produced 18 peer‐reviewed publications with female undergraduate first authors and over 100 conference presentations, including 9 international conference presentations. While Professor Cafiero does all he can to support these students, he attributes the continuous success of the group in recruiting, retaining, and supporting these women to the students themselves. The students' success and visibility on campus helps to recruit new students. The heavy presence of women in this group provides a strong support system for women who may otherwise feel isolated in a male‐dominated field; and these support groups provide models and support for women to overcome common obstacles that women in science face. We will profile three recent graduates who will discuss how the above points affected them during their time in the research group and discuss their experience in the context of some literature on women in Science, Technology, Engineering and Mathematics.
Enabling allogeneic therapies: CIRM-funded strategies for immune tolerance and immune evasion
Authors: Kadyk Lisa C. , Okamura Ross M. , Talib Sohel
Published: June 2020

A major goal for the field of regenerative medicine is to enable the safe and durable engraftment of allogeneic tissues and organs. In contrast to autologous therapies, allogeneic therapies can be produced for many patients, thus reducing costs and increasing availability. However, the need to overcome strong immune system barriers to engraftment poses a significant biological challenge to widespread adoption of allogeneic therapies. While the use of powerful immunosuppressant drugs has enabled the engraftment of lifesaving organ transplants, these drugs have serious side effects and often the organ is eventually rejected by the recipient immune system. Two conceptually different strategies have emerged to enable durable engraftment of allogeneic therapies in the absence of immune suppression. One strategy is to induce immune tolerance of the transplant, either by creating “mixed chimerism” in the hematopoietic system, or by retraining the immune system using modified thymic epithelial cells. The second strategy is to evade the immune system altogether, either by engineering the donor tissue to be “invisible” to the immune system, or by sequestering the donor tissue in an immune impermeable barrier. We give examples of research funded by the California Institute for Regenerative Medicine (CIRM) in each of these areas, ranging from early discovery-stage work through clinical trials. The advancements that are being made in this area hold promise that many more patients will be able to benefit from regenerative medicine therapies in the future.

Significance statement For cell and tissue therapies to become widely accessible will ultimately require the success of off-the-shelf allogeneic products that can be administered to patients regardless of immune compatibility with the donor tissue. Since the long-term use of immunosuppressive drugs renders patients subject to infectious disease and other side effects, it is critical to develop alternative methods to overcome immune barriers to engraftment. The California Institute for Regenerative Medicine (CIRM) has funded multiple programs, in different disease areas and at different stages of therapeutic development, that are tackling this challenge. This article summarizes the main approaches that are being taken in this rapidly moving field and gives examples of specific programs that CIRM has funded in these different areas.
Consumption of Meretrix meretrix (Linnaeus 1758) by selective shell size reduces heavy metal toxicity risk and overfishing in Tawau, North Borneo
Authors: Hamdan Diana Demiyah Mohd , Udin Laila , Musa Fazilah , Tair Rohana
Published: June 2020

Meretrix meretrix can accumulate heavy metals from the contaminated environment in its tissues and passed on these elements through the food chain, which can cause health hazards. The mean size distribution of the M. meretrix wild population at Batu Payung, Tawau, North Borneo, was determined by the linear morphometric analysis of outer shell length, and bivalve was categorized by the outer shell length size at 5‐mm interval cluster groups. The selected heavy metals concentration in wild M. meretrix whole tissues was determined by an Induced Couple Plasma‐Optical Emission Spectrometer (ICP‐OES) to provide baseline data for policymakers and stakeholders to formulate sustainable harvest management. The largest group of outer shell size (45.00–50.00 mm) had the concentration of the least heavy metals in its tissues among other smaller shell size cluster groups, indicating M. meretrix outer shell length size of more than 45 mm cleanse excessive heavy metals out of their body more efficiently. A negative correlation between nonessential heavy metals (Cd, Pb) concentration in M. meretrix edible tissues and its outer shell length size signified that the largest group of outer shell size was safer to consume. M. meretrix is also facing overfishing like elsewhere in North Borneo.
Effects of exposure to anionic surfactants (SDBS and SDS) on nitrogen removal of aerobic denitrifier
Authors: Yin Chao , Li Ying , Zhang Tingyue , Liu Jiamin , Yuan Yuxin , Huang Minsheng
Published: June 2020

In order to explain the effect of anionic surfactants on aerobic denitrification in the urban river, sodium dodecyl benzene sulfonate (SDBS) and sodium dodecyl sulfonate (SDS) were added in aerobic denitrifier and the efficiency of nitrogen removal, microbial mechanisms, and enzyme activity was investigated in this study. The results showed that the total nitrogen (TN) and the nitrate nitrogen () removal efficiency decreased as an increase of SDBS concentration. In contrast, 59.70% of the TN and 75.12% of were removed as the SDBS was 0 mg/L (Control). When SDBS was 200 mg/L (SDBS‐200), the removal efficiency of TN and was reduced to 4.92% and 4.00%, respectively. However, the denitrification efficiency was significantly accelerated when the concentration of SDS increased, except for 200 mg/L treatment (SDS‐200). As the SDS increased from 0 to 100 mg/L (SDS‐100), the removal efficiency of TN and raised from 59.70% to 70.8% and from 75.12% to 85.08%, respectively. The community structure of aerobic denitrifiers was significantly affected in the SDBS and SDS. While the Cupriavidus and Achromobacter were dominant genera in the group of Control (39.59%, and 42.45%) and SDS‐100 (44.40% and 34.86%), the relative abundance of Cupriavidus increased to 84.06% and 59.45% in the group of SDBS‐200 and SDS‐200, respectively. Enzyme activity assays proved that the nitrite reductase (NiR) relative activity of aerobic denitrification was suppressed by both SDBS and SDS. The increase in the SDS concentrations (from 0 to 50 mg/L) resulted in sharp growth of the nitrate reductase (NR) relative activities (from 100% to 146.86%). These findings demonstrated that SDBS and SDS affected aerobic denitrification efficiency of the aerobic denitrifiers by changing its microbial community structure and enzyme activity.

Practitioner points

SDS strengthened aerobic denitrification at low concentration, but the aerobic denitrifiers were inhibited in SDBS.

The variation of community structure played a vital role in the aerobic denitrification system.

The enzyme activity was seriously affected by SDBS and SDS.

Microorganisms and enzyme activity were synergistically involved in the aerobic denitrification.
Moderating effect of internal integration on the relationship of purchase social responsibility, organizational learning, and purchase performance: A study on the food industry
Authors: Wekke Ismail Suardi , Deeprasert Direk , Saregar Antomi
Published: June 2020

The objective of the current study is to investigate whether internal integration (II) is significantly moderated purchase social responsibility (PSR), organizational learning (OL), and purchasing performance (PP) in the Indonesian food industry. To this end, data from 290 supply chain (SC) managers working in the Indonesian food industry were collected by using a simple random sampling technique, which yielded a 93.54% response rate. To analyze the results, Smart PLS 3 software and structural equation modeling (SEM) was employed. The SEM findings showed a positive and significant association of PSR and OL with PP. Furthermore, II did not have a moderating effect in relation to PSR, OL, and PP. The findings suggest that PSR adoption could affect operations for both buyers and suppliers. Furthermore, organizations should realize the effect of PSR practices besides the effect of purchasing practices on PP. This study contributes a body of knowledge in the way of empirical findings. Research limitations and future directions are also formulated.
Nonlocal Timoshenko simply supported beam: Second spectrum and modes
Authors: Claeyssen Julio R. , Tolfo Daniela de R. , Copetti Rosemaira D.
Published: June 2020

We investigate the spectrum of frequencies of a nonlocal simply supported Timoshenko beam. When the mass matrix term is nonsingular, we can find the amplitudes of free vibrations as solutions of a second‐order matrix differential equation. These solutions are given in terms of a fundamental basis involving an impulsive matrix response and its derivative. This latter is given in closed‐form, involving a scalar function, its derivatives and coupling matrices. Simply supported boundary conditions have a nonclassical nature, but the frequencies are natural due to the influence of the nonlocal parameter. From the characteristic equation, we can find two branches of nonlocal frequencies referred to as the first and second spectrum and a critical frequency. This latter is the same cut‐off frequency for waves solutions of the nonlocal beam without boundary conditions. The nonlocal spectra are bounded, in contrast with the unbounded spectra of a local beam. For classifying eigenvalues as simple or double, the scalar wave function is useful. Simple eigenvalues occur when only one of the basic roots of the nonlocal characteristic polynomial are harmonically spaced, and double when both are harmonic and different. The eigenmodes have been found for both branches of the spectrum, and they are always oscillatory. At the critical frequency, the shape modes are determined by a limit process with the scalar function, resulting in occurrence the one pure‐shear mode. For a singular mass matrix, modes will exist for certain values of the nonlocal parameter but they are not unique.
New wave-type mechanism of saltatory conduction in myelinated axons and micro-saltatory conduction in C fibres
Authors: Jacak J. E. , Jacak W. A.
Published: June 2020

We present a new wave-type model of saltatory conduction in myelinated axons. Poor conductivity in the neuron cytosol limits electrical current signal velocity according to cable theory, to 1–3 m/s, whereas saltatory conduction occurs with a velocity of 100–300 m/s. We propose a wave-type mechanism for saltatory conduction in the form of the kinetics of an ionic plasmon-polariton being the hybrid of the electro-magnetic wave and of the synchronized ionic plasma oscillations in myelinated segments along an axon. The model agrees with observations and allows for description of the regulatory role of myelin. It explains also the mechanism of conduction deficiency in demyelination syndromes such as multiple sclerosis. The recently observed micro-saltatory conduction in ultrathin unmyelinated C fibers with periodic ion gate clusters is also explained.
Impact of stem design and cementation on postoperative femoral antetorsion in 227 patients with total hip arthroplasty (THA)
Authors: Fischer Tim , Stern Christoph , Fritz Benjamin , Zingg Patrick O. , Pfirrmann Christian W. A. , Sutter Reto
Published: June 2020

Objective

In total hip arthroplasty (THA), surgeons attempt to achieve a physiological antetorsion. However, postoperative antetorsion of the femoral stem is known to show large variabilities. The purpose of this study was to assess whether postoperative antetorsion is influenced by stem design or cementation.

Materials and methods

This retrospective study included 227 patients with a hip prosthesis with five different stem designs (S1: short curved, S2 and S3: standard straight, S4: standard straight collared, S5: cemented straight), who had metal suppressed 1.5T-MRI of the hip between February 2015 and October 2019. Measurement of femoral antetorsion was done independently by two fellowship-trained radiologists on axial images by measuring the angle between the long axis of the femoral neck and the posterior condylar tangent of the knee. Measured angles in the different groups were compared using the t test for independent samples.

Results

The cementless collared stem S4 showed the highest antetorsion with 18.1° (± 10.5°; range –10°–45°), which was significantly higher than the antetorsion of the collarless S3 with 13.3° (± 8.4°; − 4°–29°) and the cemented S5 with 12.7° (± 7.7°; − 3°–27°) with p = 0.012 and p = 0.007, respectively. S1 and S2 showed an antetorsion of 14.8° (± 10.0°; 1°–37°) and 14.1° (± 12.2°; − 20°–41°). The torsional variability of the cementless stems (S1–4) was significantly higher compared with that of the cemented S5 with a combined standard deviation of 10.5° and 7.7° (p = 0.019).

Conclusion

Prosthesis design impacts the postoperative femoral antetorsion, with the cementless collared stem showing the highest antetorsion. Cemented stems demonstrated significantly lower variability, suggesting the lowest rate of inadvertent malrotation.
Frequency distribution in intraoperative stimulation-evoked EMG responses during selective dorsal rhizotomy in children with cerebral palsy—part 2: gender differences and left-biased asymmetry
Authors: Wolter Simone , Haberl Hannes , Spies Claudia , Sargut T. Alp , Martin John H. , Tafelski Sascha , van Riesen Anne , Küchler Ingeborg , Wegner Brigitte , Scholtz Kathrin , Thomale Ulrich-W. , Michael Theodor , Murphy James F. , Schulz Matthias
Published: June 2020

Introduction

Spinal reflexes reorganize in cerebral palsy (CP), producing hyperreflexia and spasticity. CP is more common among male infants, and gender might also influence brain and spinal–cord reorganization. This retrospective study investigated the frequency of higher-graded EMG responses elicited by electrical nerve–root stimulation during selective dorsal rhizotomy (SDR), prior to partial nerve– root deafferentation, considering not only segmental level and body side, but also gender.

Methods

Intraoperative neuromonitoring (IOM) was used in SDR to pinpoint the rootlets most responsible for exacerbated stimulation-evoked EMG patterns recorded from lower-limb muscle groups. Responses were graded according to an objective response-classification system, ranging from no abnormalities (grade 0) to highly abnormal (grade 4+), based on ipsilateral spread and contralateral involvement. Non-parametric analysis of data with repeated measures was primarily used in investigating the frequency distribution of these various EMG response grades. Over 7000 rootlets were stimulated, and the results for 65 girls and 81 boys were evaluated, taking changes in the composition of patient groups into account when considering GMFCS levels.

Results

The distribution of graded EMG responses varied according to gender, laterality, and level. Higher-graded EMG responses were markedly more frequent in the boys and at lower segmental levels (L5, S1). Left-biased asymmetry in higher–graded rootlets was also more noticeable in the boys and in patients with GMFCS level I. A close link was observed between higher-grade assessments and left-biased asymmetry.

Conclusions

Detailed insight into the patient’s initial spinal-neurofunctional state prior to deafferentation suggests that differences in asymmetrical spinal reorganization might be attributable to a hemispheric imbalance.
Europe-wide precipitation projections at convection permitting scale with the Unified Model
Authors: Chan Steven C. , Kendon Elizabeth J. , Berthou Ségolène , Fosser Giorgia , Lewis Elizabeth , Fowler Hayley J.
Published: June 2020

For the first time, we analyze 2.2 km UK Met Office Unified Model convection-permitting model (CPM) projections for a pan-European domain. These new simulations represent a major increase in domain size, allowing us to examine the benefits of CPMs across a range of European climates. We find a change to the seasonality of extreme precipitation with warming. In particular, there is a relatively muted response for summer, which contrasts with much larger increases in autumn and winter. This flattens the hourly extreme precipitation seasonal cycle across Northern Europe which has a summer peak in the present climate. Over the Western Mediterranean, where autumn is the main extreme precipitation season, there is a regional increase in hourly extreme precipitation frequency, but local changes for lower precipitation thresholds are often insignificant. For mean precipitation, decreases are projected across Europe in summer, smaller decreases in autumn, and increases in winter; comparable changes are seen in the driving general circulation model (GCM) simulations. The winter mean increase is accompanied by a large decrease of winter mean snowfall. Comparing the driving GCM projections with the CPM ones, the CPMs show a robust enhanced intensification of precipitation extremes at the convection-permitting scale compared to coarser resolution climate model projections across various European regions for summer and autumn.
Relationship between stroke etiology and collateral status in anterior circulation large vessel occlusion
Authors: Hassler Eva , Kneihsl Markus , Deutschmann Hannes , Hinteregger Nicole , Magyar Marton , Wießpeiner Ulrike , Haidegger Melanie , Fandler-Höfler Simon , Eppinger Sebastian , Niederkorn Kurt , Enzinger Christian , Fazekas Franz , Gattringer Thomas
Published: June 2020

Background and purpose

Clinical outcome after mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke is influenced by the intracerebral collateral status. We tested the hypothesis that patients with preexisting ipsilateral extracranial carotid artery stenosis (CAS) would have a better collateral status compared to non-CAS patients. Additionally, we evaluated MT-related adverse events and outcome for both groups.

Methods

Over a 7-year period, we identified all consecutive anterior circulation MT patients (excluding extracranial carotid artery occlusion and dissection). Patients were grouped into those with CAS ≥ 50% according to the NASCET criteria and those without significant carotid stenosis (non-CAS). Collateral status was rated on pre-treatment CT- or MR-angiography according to the Tan Score. Furthermore, we assessed postinterventional infarct size, adverse events and functional outcome at 90 days.

Results

We studied 281 LVO stroke patients, comprising 46 (16.4%) with underlying CAS ≥ 50%. Compared to non-CAS stroke patients (n = 235), patients with CAS-related stroke more often had favorable collaterals (76.1% vs. 46.0%). Recanalization rates were comparable between both groups. LVO stroke patients with underlying CAS more frequently had adverse events after MT (19.6% vs. 6.4%). Preexisting CAS was an independent predictor for favorable collateral status in multivariable models (Odds ratio: 3.3, p = 0.002), but post-interventional infarct size and functional 90-day outcome were not different between CAS and non-CAS patients.

Conclusions

Preexisting CAS ≥ 50% was associated with better collateral status in LVO stroke patients. However, functional 90-day outcome was independent from CAS, which could be related to a higher rate of adverse events.