bluuebunny/crossref_metadata_2025 huggingface dataset:
Regioselective C4 and C6 Double Oxidation of Cellulose by Lytic Polysaccharide Monooxygenases
Authors: Sun Peicheng , Laurent Christophe V. F. P. , Boerkamp Vincent J. P. , van Erven Gijs , Ludwig Roland , van Berkel Willem J. H. , Kabel Mirjam A.
Published: December 2021

Lytic polysaccharide monooxygenases (LPMOs) play a key role in enzymatic degradation of hard‐to‐convert polysaccharides, such as chitin and cellulose. It is widely accepted that LPMOs catalyze a single regioselective oxidation of the C1 or C4 carbon of a glycosidic linkage, after which the destabilized linkage breaks. Here, a series of novel C4/C6 double oxidized cello‐oligosaccharides was discovered. Products were characterized, aided by sodium borodeuteride reduction and hydrophilic interaction chromatography coupled to mass spectrometric analysis. The C4/C6 double oxidized products were generated by C4 and C1/C4 oxidizing LPMOs, but not by C1 oxidizing ones. By performing incubation and reduction in H218O, it was confirmed that the C6 gem‐diol structure resulted from oxygenation, although oxidation to a C6 aldehyde, followed by hydration to the C6 gem‐diol, could not be excluded. These findings can be extended to how the reactive LPMO‐cosubstrate complex is positioned towards the substrate.
A survey of step length estimation models based on inertial sensors for indoor navigation systems
Authors: Soni Rakesh , Trapasiya Samir
Published: December 2021

In many applications (i.e., navigation of vehicles in traffic, museum guide, guidance to firefighters in poor visibility, and elderly care assistance systems), location‐based services (LBS) rely on the global positioning system (GPS) for accurate positioning. LBS can be challenging to employ in an indoor environment because of the lack of a line‐of‐sight (LOS) component and other signal propagation issues. Over the last decade, researchers worldwide have been motivated to solve the problem of continuous indoor positioning in situations when GPS is ineffective. We thoroughly reviewed research conducted by many scholars and compiled this survey article, which provides a comprehensive overview of indoor pedestrian navigation systems, prevalent step length estimation models, and the current state of the art. There are two key strategies in which substantial work on indoor localization is carried out. One is a dead reckoning in which the present location of the pedestrian is calculated based on details about previous location, and the other is an inertial navigation system in which the forward acceleration from an inertial sensor strapped down to the user's body is integrated twice to establish the current location. The step length is a crucial component of the inertial sensor‐based navigation in both these strategies. For different users, step length is variable and also changes at different walking speeds for each user. As a result, the focus of this survey is on step length estimation models. The survey describes and compares various approaches to estimating step length from various perspectives, including the research method used, the length of the test path, various walking speeds, the location of the sensor device on the user's body, and the accuracy achieved in estimating step length. Because inertial sensors are embedded in smartphones, it is vital to identify the smartphone mode (i.e., phoning, texting, or pocket) during each step taken while using smartphone‐based indoor navigation. The report concludes with a quantitative evaluation of the performance of smartphone mode recognition modules. At the end, we list out challenges still to be addressed for scholars working on indoor navigation.
Novel strategies to oral delivery of insulin: Current progress of nanocarriers for diabetes management
Authors: Abdel‐Moneim Adel , Ramadan Hanaa
Published: December 2021

Diabetes mellitus is one of the most serious public health problems in the world. Repeated daily injections of subcutaneous insulin is the standard treatment for patients with type 1 diabetes mellitus; however, subcutaneous insulin injections can potentially cause local discomfort, patient noncompliance, hypoglycemia, failure to regulate glucose homeostasis, infections, and fat deposits at the injection sites. In recent years, numerous attempts have been made to produce safe and efficient nanoparticles for oral insulin delivery. Oral administration is considered the most effective alternative route to insulin injection, but it is accompanied by several challenges related to enzymatic proteolysis, digestive breakdown, and absorption barriers. A number of natural and synthetic polymeric, lipid‐based, and inorganic nanoparticles have been investigated for use. Although improvements have recently been made in potential oral insulin delivery systems, these require further investigation before clinical trials are conducted. In this review, new approaches to oral insulin delivery for diabetes treatment are discussed, including polymeric, lipid‐based, and inorganic nanoparticles, as well as the clinical trials performed for this purpose.
Phylogeography of the Japanese greater horseshoe bat Rhinolophus nippon (Mammalia: Chiroptera) in Northeast Asia: New insight into the monophyly of the Japanese populations
Authors: Ikeda Yugo , Motokawa Masaharu
Published: December 2021

The Japanese greater horseshoe bat (Rhinolophus nippon) is distributed widely in East Asia. Within the species, R. nippon in Northeast Asia is regarded as the lineage that diverged most recently. However, the monophyly of the Japanese populations is unclear due to insufficient data about phylogenetic relationship of the western Japanese populations. To test the monophyly of the Japanese populations of R. nippon, we sampled R. nippon from western Japan and performed a phylogeographic analysis based on mitochondrial DNA cytochrome b and the D‐loop. The Northeast Asian lineage consisted of three main clades in eastern Japan (clade I), western Japan (clade II), and the continent as well as the Kumamoto population in westernmost Japan (clade III). The results of this study do not support the monophyly of the Japanese population. The findings suggest the “reverse colonization” of R. nippon from the Japanese Archipelago to the Eurasian continent, and provide important insight into the role of the island system in creation and supply of diversity to the continent.
Above‐ and below‐ground biodiversity responses to the prolonged flood pulse in central‐western Amazonia, Brazil
Authors: Bredin Yennie K. , Hess Laura L. , Scabin Andressa B. , Dunthorn Micah , Haugaasen Torbjørn , Peres Carlos A. , Nilsson Henrik R. , Antonelli Alexandre , Ritter Camila D.
Published: December 2021

Amazonia encompasses extensive forests in areas that are periodically inundated by overflowing rivers. The inundation depth and duration vary according to the slope of the terrain and distance to major water bodies. This creates a flooding gradient from the lowest lying seasonally flooded forest up into the unflooded forest, which directly affects the biota. However, the effect of this gradient on soil organisms remains elusive. Here, we use DNA metabarcoding to estimate prokaryote and eukaryote diversity from soil and litter samples along the flooding gradient in central‐western Amazonia using 16S and 18S gene sequences, respectively. We characterize the below‐ground diversity and community composition based on amplicon sequence variants (ASVs). We examine relationships between the soil biota and the flooding gradient, soil properties, and above‐ground woody plant diversity. The flooding gradient does not explain below‐ground biodiversity, nor is below‐ground diversity explained by the above‐ground woody plant diversity. We uncover several taxonomic groups—such as Patescibacteria—not previously reported from Amazonian seasonally flooded forests. The flooding gradient and woody plant diversity partly explain the community composition of soil bacteria. Although the effects of the flooding gradient, soil properties, and above‐ground woody plant diversity are difficult to quantify, our results indicate that flood stress may influence below‐ground bacterial community composition.
Synthesis, Structure and Cu‐Phenylacetylide Coordination of an Unsymmetrically Substituted Bulky dppf‐Analog
Authors: Dey Subhayan , Roesler Fabian , Höfler Mark V. , Bruhn Clemens , Gutmann Torsten , Pietschnig Rudolf
Published: December 2021

The donor properties of a set of bulky ferrocene based bisphosphanes (Fe(C5H4PMes2)2 and (C5H4PMes2)Fe(C5H4PtBu2 with Mes= mesityl and tBu=tert‐butyl) were probed by exploring the NMR parameters of the corresponding selenophosphoranes amended by cyclovoltammetry. The ligand properties were explored in the complexation of copper phenylacetylide which is relevant as intermediate in the Cu(I) catalyzed CO2 addition to phenylacetylene. Owing to the poor solubility of the resulting complexes their characterization was performed with solid state NMR spectroscopy amended by IR spectroscopy, mass spectrometry and elemental analysis. Remarkably, these complexes feature luminescent properties, albeit with limited quantum yield.
Development a multiplex panel of AISNPs, multi‐allelic InDels, microhaplotypes, and Y‐SNP/InDel loci for multiple forensic purposes via the NGS
Authors: Jin Xiao‐Ye , Liu Yan‐Fang , Cui Wei , Chen Chong , Zhang Xing‐Ru , Huang Jiang , Zhu Bo‐Feng
Published: December 2021

Recently, next generation sequencing has shown the promising application value in forensic research. In this study, we constructed a multiplex amplification system of different molecular genetic markers based on the previous selected ancestry informative single nucleotide polymorphisms (SNPs), multi‐allelic insertion/deletion (InDel) polymorphisms, microhaplotypes, and Y‐chromosomal SNP/InDel loci, and evaluated forensic efficiencies of the system in Chinese Shaanxi Han, Chinese Hui, and Chinese Mongolian groups via the next generation sequencing platform. Ancestry information analyses of Shaanxi Han, Hui, and Mongolian groups revealed that most Mongolian individuals could be differentiated from Shaanxi Hans and Huis based on the selected ancestry informative SNPs. Multi‐allelic InDels and microhaplotypes showed the multiple allele variations and possessed relatively high genetic polymorphisms in these three groups, indicating these loci could provide higher forensic efficiencies for individual identification and paternity testing. Based on Y‐chromosomal SNPs, different haplogroup distributions were observed among Shaanxi Han, Hui, and Mongolian groups. In conclusion, the self‐developed system could be used to simultaneously carry out the individual identification, paternity analysis, mixture deconvolution, forensic ancestry information analysis, and Y‐chromosomal haplogroup inference, which could provide more valuable investigative clues in forensic practices.
Effects and interactions of metal oxides in microparticle‐enhanced cultivation of filamentous microorganisms
Authors: Laible Andreas Reiner , Dinius Anna , Schrader Marcel , Krull Rainer , Kwade Arno , Briesen Heiko , Schmideder Stefan
Published: December 2021

Filamentous microorganisms are used as molecular factories in industrial biotechnology. In 2007, a new approach to improve productivity in submerged cultivation was introduced: microparticle‐enhanced cultivation (MPEC). Since then, numerous studies have investigated the influence of microparticles on the cultivation. Most studies considered MPEC a morphology engineering approach, in which altered morphology results in increased productivity. But sometimes similar morphological changes lead to decreased productivity, suggesting that this hypothesis is not a sufficient explanation for the effects of microparticles. Effects of surface chemistry on particles were paid little attention, as particles were often considered chemically‐inert and bioinert. However, metal oxide particles strongly interact with their environment. This review links morphological, physical, and chemical properties of microparticles with effects on culture broth, filamentous morphology, and molecular biology. More precisely, surface chemistry effects of metal oxide particles lead to ion leaching, adsorption of enzymes, and generation of reactive oxygen species. Therefore, microparticles interfere with gene regulation, metabolism, and activity of enzymes. To enhance the understanding of microparticle‐based morphology engineering, further interactions between particles and cells are elaborated. The presented description of phenomena occurring in MPEC eases the targeted choice of microparticles, and thus, contributes to improving the productivity of microbial cultivation technology.
Drug‐resistant epilepsy and the hypothesis of intrinsic severity: What about the high‐frequency oscillations?
Authors: Santana‐Gomez Cesar E. , Engel Jerome , Staba Richard
Published: December 2021

Drug‐resistant epilepsy (DRE) affects approximately one‐third of the patients with epilepsy. Based on experimental findings from animal models and brain tissue from patients with DRE, different hypotheses have been proposed to explain the cause(s) of drug resistance. One is the intrinsic severity hypothesis that posits that drug resistance is an inherent property of epilepsy related to disease severity. Seizure frequency is one measure of epilepsy severity, but frequency alone is an incomplete measure of severity and does not fully explain basic research and clinical studies on drug resistance; thus, other measures of epilepsy severity are needed. One such measure could be pathological high‐frequency oscillations (HFOs), which are believed to reflect the neuronal disturbances responsible for the development of epilepsy and the generation of spontaneous seizures. In this manuscript, we will briefly review the intrinsic severity hypothesis, describe basic and clinical research on HFOs in the epileptic brain, and based on this evidence discuss whether HFOs could be a clinical measure of epilepsy severity. Understanding the mechanisms of DRE is critical for producing breakthroughs in the development and testing of novel strategies for treatment.
Does cesarean delivery increase the occurrence of neurodevelopmental disorders in childhood?
Authors: Chen Ginden , Chiang Wan‐Lin , Chiang Tung‐liang
Published: December 2021

Objective

This study aimed to investigate whether cesarean delivery (CD) is associated with the occurrence of neurodevelopmental disorders (NDDs) at the age of 8 years.

Methods

A total of 19 142 children were included from the Taiwan Birth Cohort Study (TBCS) database. Associations between modes of delivery or modalities of CD and NDDs were evaluated before and after controlling for gestational age (GA) and clinical condition at birth, children's characteristics, maternal socioeconomic status and maternal clinical condition at childbirth.

Results

The odds ratio (OR) of occurrence of NDDs in children born via CD was 1.15 and the 95% confidence interval (CI) was 1.00–1.32. Emergency CD had a higher occurrence of NDDs (OR: 1.38; 95% CI: 1.16–1.65) compared with vaginal delivery. These associations were attenuated after controlling for children's and maternal characteristics and GA at birth. GA at birth had a significant reverse dose‐effect on the occurrence of NDDs in children born via vaginal delivery and CD.

Conclusion

Modes of delivery and GA could influence the occurrence of NDDs in childhood. However, association of risk of NDDs and modes of delivery or modalities of CD might be modified by males, lower socioeconomic status and mothers with gestational diabetes mellitus.
Prophylactic negative pressure wound therapy on surgical site infection in obese women after cesarean section: A systematic review and meta‐analysis
Authors: Guo Chenchen , Cheng Tao , Li Junsheng
Published: December 2021

Prevention of surgical site infection (SSI) is a public health challenge. The objective of the study was to evaluate the efficacy of negative pressure wound therapy (NPWT) for preventing SSI and other wound complications in obese women undergoing cesarean section. The search terms included “negative pressure wound therapy”, “obesity” and “cesarean section/delivery”. Randomized controlled trials were used to compare the use of NPWT to standard dressings in preventing SSI in obese women after cesarean section. A comprehensive literature search of four databases was performed up to June 2021. The primary outcome was SSI. Secondary outcomes were seroma, hematoma, overall wound complications, and adverse skin reactions. Ten RCTs involving 5586 patients met the inclusion criteria. The use of NPWT reduced SSI (RR = 0.76, 95%CI: 0.63–0.92, P = 0.004). No statistically significant difference was detected in the incidence of overall wound complications (RR = 0.93, P = 0.48), seroma (RR = 1.10, P = 0.79), hematoma (RR = 0.63, P = 0.36) and hospital readmission (RR = 1.41, P = 0.15). NPWT significantly increased the occurrence of skin blistering with a RR of 4.60 (P = 0.04). Use of prophylactic NPWT after cesarean delivery among obese women is associated with a significant reduction of surgical site infection.
Toward global digital literate citizens: A case of Thailand's aging generation
Authors: Jantavongso Suttisak
Published: December 2021

Digital technology offers solutions for enhancing older adults' wellbeing. Older adults need digital knowledge and skills to ensure the quality of life, increase cognitive engagement in daily routines, and better connection with loved ones. Thailand is moving toward a knowledge‐based economy, and the Thai government has declared interest in digital ecosystem development. Therefore, emphasis must be placed on the older adults and other underprivileged living in remote areas. However, to date, there are few comprehensive studies on the levels of digital competency and on how older adults accept and use digital technologies. For this reason, this paper constructed a model demonstrating the digital literacy competency among Thai older adults in rural areas. The exploratory research examined the older adults' digital competencies through 97 interviews. Moreover, the results revealed the existing competency gap. The top three desired digital competencies were safety, communication and collaboration, and information and data literacy. Examining these findings nurtures the formation of digital literacy competency from the needs of older adults. Thus, the results contribute to scholarship on workable digital literacy curriculum development designed especially for older adults and help Thailand achieve its vision of “Digital Thailand” that all Thais will become digitally literate.
Diagnostic comparison between cord blood and filter paper for the screening of congenital hypothyroidism
Authors: Alameer Seham , Althobaiti Eman , Alshaikh Saud , Turjoman Meshari , Badriq Feras , AlSofyani Abeer , Mujalled Mohammed , Borai Anwar
Published: December 2021

Background

Cord‐blood and heel‐prick TSH levels are essential in diagnosing and preventing the serious complications of congenital hypothyroidism, which mainly include intellectual disability. The study aimed to compare between cord‐blood and heel‐prick TSH sensitivity and specificity in detecting congenital hypothyroidism (CH) among newborn screened babies.

Method

The study included 21,012 newborn screened babies for congenital hypothyroidism starting from September 2013 until March 2019. Both cord‐blood and heel‐prick TSH were collected from each newborn. Heel prick and cord‐blood TSH cutoff values of >21 μU/ml and >30 mIU/L respectively were considered positive.

Results

Out of the total screened newborns, 12 were confirmed for having primary congenital hypothyroidism. Nine cases were positive for cord‐blood TSH (Sensitivity 75%, specificity 99.9%, and a recall rate of 0.004%), while 139 cases were positive for heel‐prick blood TSH (Sensitivity of 100%, specificity of 99.3%, and a recall rate of 0.60%).

Conclusion

For the screening of CH, heel prick is considered a superior method, but cord blood remains a practical option due to its cost‐effectiveness, immediate action, and lower recall rate. Therefore, whenever recall is difficult and/or early discharge is the practice, cord blood is an alternative method to heel prick but not with cases of prematurity.
Effects of advance notice on transition‐related pausing in pigeons
Authors: Toegel Forrest , Perone Michael
Published: December 2021

Transitions between tasks can produce behavioral disruptions that are characterized as problematic. Advance notice, a procedure designed to reduce disruptions, involves presenting a stimulus to warn of the end of the ongoing activity and the nature of the upcoming activity. Clinical evaluations of advance notice have produced mixed results. We studied advance notice in a controlled laboratory setting. Pigeons' keypecking was maintained on a multiple schedule with 2 fixed‐ratio components. In the lean component, completing the ratio produced brief access to food; in the rich component, completing the ratio produced longer access. Disruptions in operant behavior, measured as pauses in pecking, were reliably produced in the transition from a rich component to a lean one. Advance notice was provided by flashing the houselight before transitions to lean components. Advance notice did not reduce pausing in the rich–lean transition; instead, it tended to increase it. When the flashing houselight warned of a transition but was equally likely to be followed by the rich component as the lean one, the stimulus had no reliable effect on pausing. Despite its limitations as a translational model of clinical settings, this experiment suggests that clinical use of advance notice should be approached with caution.
Synthesis, and reverse screening of 6‐(3,4,5‐trimethoxyphenyl)pyrimidine‐5‐carbonitrile derivatives as anticancer agents: Part‐II
Authors: Nainwal Lalit Mohan , Shaququzzaman Mohammad , Akhter Mymoona , Husain Asif , Parvez Suhel , Tasneem Sharba , Iqubal Ashif , Alam Mohammad Mumtaz
Published: December 2021

In continuation to our previous studies on cyanopyrimidine derivatives as anticancer agents, we further designed, synthesized, and evaluated new 3,4,5‐trimethoxy phenyl ring pendant sulfur‐containing cyanopyrimidine derivatives (4a–m) with a particular lipophilic behavior. In this work, we have varied the chain length from isopropyl to isopentyl and evaluated their anticancer activities. To study the antiproliferative spectrum, in vitro evaluation was piloted against a panel of 60 cancer cell lines at the National Cancer Institute, United States. Compound 4g (NSC: D‐813664) displayed the most promising broad‐spectrum anticancer activity with high growth inhibition of various cell lines representing action against multiple cancers diseases. It showed percentage growth inhibition of 84.01 and 76.94 against SR leukemia and HCT‐116 colon cancer cell lines. Absorption, distribution, metabolism, excretion, and toxicity studies and reverse screening were also performed to identify the potential targets of designed molecules. It was concluded that 6‐(3,4,5‐trimethoxyphenyl) pyrimidine‐5‐carbonitrile derivatives exhibited its anticancer activity through different targets and hence could be further structurally modified and optimized to develop more potent multi‐targeting anticancer agents.
Insight on molecular pathogenesis and pharmacochaperoning potential in phosphomannomutase 2 deficiency, provided by novel human phosphomannomutase 2 structures
Authors: Briso‐Montiano Alvaro , Del Caño‐Ochoa Francisco , Vilas Alicia , Velázquez‐Campoy Adrián , Rubio Vicente , Pérez Belén , Ramón‐Maiques Santiago
Published: December 2021

Phosphomannomutase 2 (PMM2) deficiency, the most frequent congenital disorder of glycosylation (PMM2‐CDG), is a severe condition, which has no cure. Due to the identification of destabilizing mutations, our group aims at increasing residual activity in PMM2‐CDG patients, searching for pharmacochaperones. Detailed structural knowledge of hPMM2 might help identify variants amenable to pharmacochaperoning. hPMM2 structural information is limited to one incomplete structure deposited in the Protein Databank without associated publication, which lacked ligands and residues from a crucial loop. Here we report five complete crystal structures of hPMM2, three for wild‐type and two for the p.Thr237Met variant frequently found among Spanish PMM2‐CDG patients, free and bound to the essential activator glucose‐1,6‐bisphosphate (Glc‐1,6‐P2). In the hPMM2 homodimer, each subunit has a different conformation, reflecting movement of the distal core domain relative to the dimerization cap domain, supporting an opening/closing process during catalysis. Two Mg2+ ions bind to the core domain, one catalytic and one structural. In the cap domain, the site for Glc‐1,6‐P2 is well delineated, while a Cl− ion binding at the intersubunit interface is predicted to strengthen dimerization. Patient‐found amino acid substitutions are nonhomogeneously distributed throughout hPMM2, reflecting differential functional or structural importance for various parts of the protein. We classify 93 of 101 patient‐reported single amino acid variants according to five potential pathogenetic mechanism affecting folding of the core and cap domains, linker 2 flexibility, dimerization, activator binding, and catalysis. We propose that ~80% and ~50% of the respective core and cap domains substitutions are potential candidates for pharmacochaperoning treatment.
Effect of plasma electrolytic oxidation on the hot salt corrosion fatigue behavior of the TC17 titanium alloy
Authors: Shi Hailan , Liu Daoxin , Zhang Xiaohua , Zhao Weidong , Liu Zhen , Li Mengyao , He Yuting
Published: December 2021

In this paper, the effect of plasma electrolytic oxidation (PEO) on the hot salt corrosion fatigue (HSCF) behavior of the TC17 titanium alloy at 420°C was investigated. Through microstructure characterization and fatigue fracture analysis, combined with a comparative study of its hot salt corrosion behavior, the mechanism of PEO on HSCF behavior was also investigated. The results showed that the high‐temperature fatigue resistance of the TC17 titanium alloy was significantly reduced by the deposition of 0.4 mg/cm2 of solid NaCl compared with that without a salt coating. This behavior was observed because the corrosion pits caused by hot salt corrosion promoted the initiation of fatigue cracks, and hydrogen penetration promoted the growth of fatigue cracks. However, the HSCF resistance of the TC17 alloy with the PEO ceramic coating could be effectively increased. This was because the PEO ceramic coating with high bonding strength and good compactness effectively inhibited hot salt corrosion damage and delayed the formation of the resident slip zone and hydrogen permeation, thereby inhibiting the initiation and propagation of fatigue cracks.
Low Voltage and Low Temperature Soft Electrothermal Actuator Based on PE/Graphite Bilayer Film
Authors: Yeli Xu , Yanni Lin , Yan Chen , Fenjing Wang
Published: December 2021

Soft electrothermal actuators are widely used in soft robots, smart switches, medical devices, artificial muscles, and human–machine interactions. Generally, they operate at room temperature but also meet the safety standards for maximum safe voltage for a human body. Therefore, an actuator with a lower voltage and lower temperature is the first choice, as long as the performance is not affected. In this study, a bilayer film based on polythene (PE)/graphite is used to realize an electrothermal drive. The method is simple, inexpensive, and convenient for mass production. At a low driving voltage of between 1.5 and 2 V, and at a temperature of 40–52 °C, a maximum bending angle of 139.22°–470°. Through the demonstration of a micromechanical gripper and transportation illustrated by drug crawling, it is proven that the PE/graphite composite membrane can be widely applied in the field of soft actuators.
Self‐management of musculoskeletal (MSK) conditions: What is most useful to patients? Protocol for a mixed methods systematic review
Authors: Wanless Ben , Berry Alice , Noblet Tim
Published: December 2021

Introduction

Musculoskeletal (MSK) conditions are the leading cause of disability in the United Kingdom, leading to ever‐growing waiting lists. Clinical guidelines highlight that most musculoskeletal conditions resolve in time and with little clinical input, and so supporting people to self‐manage is recommended to optimise healthcare resources. Despite this, the term self‐management remains ambiguous and to date no systematic review has evaluated if self‐management is a suitable, acceptable, and effective intervention/strategy for managing all MSK conditions.

Methods and Analysis

This protocol is informed and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA). An advanced convergent qualitative meta‐integration mixed‐studies design will be used. Using a comprehensive predetermined search strategy, databases, key journals and grey literature will be searched independently by two reviewers. The reviewers will independently assess eligibility, complete data extraction, and evaluate for risk of bias using the Mixed Methods Appraisal Tool (MMAT). The overall quality of included studies will be evaluated using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines. Data from mixed‐methods studies will be transformed using a process of fractionation and analysed alongside the data extracted from the quantitative and qualitative studies, using descriptive analysis and thematic analysis, respectively.

Ethics and dissemination

No research ethics are required for this systematic review since patient data will not be collected. The review will help to inform healthcare professionals and researchers on the most suitable, acceptable, and effective intervention/strategy for self‐managing MSK conditions. Results of this review will be submitted for publication in a peer‐reviewed journal and conference presentations.
Optimal stimulation site of the femoral nerve to record F waves from the vastus lateralis muscle
Authors: Kurobe Masataka , Matsubara Hiroyuki , Suzuki Toshiaki
Published: December 2021

Introduction/Aims

The conventional recording of F waves from the vastus lateralis muscle (VL) may not accurately measure the F‐wave amplitude, as the F‐wave latency is short and overlaps with the M wave. However, the optimal stimulation site of the femoral nerve for recording M and F waves separately from the VL remains unclear. In this study we aimed to determine the optimal stimulation site of the femoral nerve to record M and F waves separately from the VL.

Methods

Stimulating electrodes were placed medial and lateral to the VL (50%, 60%, 70%, and 80% of the distance along a line extending from the proximal to the distal thigh). Each site of the distal thigh was electrically stimulated at random and F waves were recorded from the VL. Each stimulation site was considered to be success if there was no severe pain or discomfort during electrical stimulation of the femoral nerve and no overlap between the recorded M and F waves; otherwise, it was determined as a failure.

Results

Thirteen healthy men participated in the study. F waves were successfully recorded in five participants at the 50% sites, eight participants at the 60% site, and 12 participants at the 70% and 80% sites. In cases of failed F‐wave measurement, the participants experienced severe pain or discomfort due to electrical stimulation.

Discussion

M and F waves could be recorded separately from the VL when the relevant branch of the femoral nerve was stimulated in the distal thigh.
Predicting outcomes after intradetrusor onabotulinumtoxina for non‐neurogenic urgency incontinence in women
Authors: Hendrickson Whitney K. , Xie Gongbo , Rahn David D. , Amundsen Cindy L. , Hokanson James A. , Bradley Megan , Smith Ariana L. , Sung Vivian W. , Visco Anthony G. , Luo Sheng , Jelovsek J. Eric
Published: December 2021

Aims

Develop models to predict outcomes after intradetrusor injection of 100 or 200 units of onabotulinumtoxinA in women with non‐neurogenic urgency urinary incontinence (UUI).

Methods

Models were developed using 307 women from two randomized trials assessing efficacy of onabotulinumtoxinA for non‐neurogenic UUI. Cox, linear and logistic regression models were fit using: (1) time to recurrence over 12 months, (2) change from baseline daily UUI episodes (UUIE) at 6 months, and (3) need for self‐catheterization over 6 months. Model discrimination of Cox and logistic regression models was calculated using c‐index. Mean absolute error determined accuracy of the linear model. Calibration was demonstrated using calibration curves. All models were internally validated using bootstrapping.

Results

Median time to recurrence was 6 (interquartile range [IQR]: 2–12) months. Increasing age, 200 units of onabotulinumtoxinA, higher body mass index (BMI) and baseline UUIE were associated with decreased time to recurrence. The c‐index was 0.63 (95% confidence interval [CI]: 0.59, 0.67). Median change in daily UUIE from baseline at 6 months was −3.5 (IQR: −5.0, −2.3). Increasing age, lower baseline UUIE, 200 units of onabotulinumtoxinA, higher BMI and IIQ‐SF were associated with less improvement in UUIE. The mean absolute error predicting change in UUIE was accurate to 1.6 (95% CI: 1.5, 1.7) UUI episodes. The overall rate of self‐catheterization was 17.6% (95% CI: 13.6%–22.4%). Lower BMI, 200 units of onabotulinumtoxinA, increased baseline postvoid residual and maximum capacity were associated with higher risk of self‐catheterization. The c‐index was 0.66 (95% CI: 0.61, 0.76). The three calculators are available at http://riskcalc.duke.edu.

Conclusions

After external validation, these models will assist clinicians in providing more accurate estimates of expected treatment outcomes after onabotulinumtoxinA for non‐neurogenic UUI in women.
Low‐order preconditioning of the Stokes equations
Authors: Voronin Alexey , He Yunhui , MacLachlan Scott , Olson Luke N. , Tuminaro Raymond
Published: December 2021

A well‐known strategy for building effective preconditioners for higher‐order discretizations of some PDEs, such as Poisson's equation, is to leverage effective preconditioners for their low‐order analogs. In this work, we show that high‐quality preconditioners can also be derived for the Taylor–Hood discretization of the Stokes equations in much the same manner. In particular, we investigate the use of geometric multigrid based on the discretization of the Stokes operator as a preconditioner for the discretization of the Stokes system. We utilize local Fourier analysis to optimize the damping parameters for Vanka and Braess–Sarazin relaxation schemes and to achieve robust convergence. These results are then verified and compared against the measured multigrid performance. While geometric multigrid can be applied directly to the system, our ultimate motivation is to apply algebraic multigrid within solvers for systems via the discretization, which will be considered in a companion paper.
Estradiol promotes cell survival and induces Greb1 expression in granulosa cell tumors of the ovary through an ERα‐dependent mechanism
Authors: Cluzet Victoria , Devillers Marie M , Petit Florence , Pierre Alice , Giton Frank , Airaud Eloïse , L'Hôte David , Leary Alexandra , Genestie Catherine , Treilleux Isabelle , Mayeur Anne , Katzenellenbogen John A , Kim Sung Hoon , Cohen‐Tannoudji Joëlle , Chauvin Stéphanie , Guigon Céline J
Published: December 2021

Granulosa cell tumor (GCT) is a form of ovarian tumor characterized by its tendency to recur years after surgical ablation. Little is known about the mechanisms involved in GCT development and progression. GCTs can produce estradiol (E2), but whether this hormone could play a role in this cancer through its nuclear receptors, i.e. ERα and ERβ, remains unknown. Here, we addressed this issue by cell‐based and molecular studies on human GCTs and GCT cell lines. Importantly, we observed that E2 significantly increased the growth of GCT cells by promoting cell survival. The use of selective agonists of each type of receptor, together with Esr1 (ERα) or Esr2 (ERβ)‐deleted GCT cells, revealed that E2 mediated its effects through ERα‐dependent genomic mechanisms and ERβ/ERα‐dependent extra‐nuclear mechanisms. Notably, the expression of Greb1, a prototypical ER target gene, was dose‐dependently upregulated by E2 specifically through ERα in GCT cells. Accordingly, using GCTs from patients, we found that GREB1 mRNA abundance was positively correlated to intra‐tumoral E2 concentrations. Tissue microarray analyses showed that there were various combinations of ER expression in primary and recurrent GCTs, and that ERα expression persisted only in combination with ERβ in ~40% of recurrent tumors. Altogether, this study demonstrates that E2 can promote the progression of GCTs, with a clear dependence on ERα. In addition to demonstrating that GCTs can be classified as a hormone‐related cancer, our results also highlight that the nature of ER forms present in recurrent GCTs could underlie the variable efficiency of endocrine therapies. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Prediction of neonatal survival according to lung‐to‐head ratio in fetuses with right congenital diaphragmatic hernia (CDH): A multicentre study from the Latin American CDH Study Group registry
Authors: Cruz‐Martínez Rogelio , Molina‐Giraldo Saulo , Etchegaray Adolfo , Ventura Walter , Pavón‐Gómez Néstor , Gil‐Guevara Enrique , Villalobos‐Gómez Rosa , Luna‐García Jonahtan , Gámez‐Varela Alma , Martínez‐Rodríguez Miguel , López‐Briones Hugo , Chávez‐González Eréndira ,   Latin American CDH Study Group
Published: December 2021

Objective

To evaluate survival outcomes of fetuses with right sided congenital diaphragmatic hernia (CDH) treated in Latin American centres and to assess the utility of left lung area to predict neonatal survival.

Methods

A retrospective cohort including isolated right sided CDH cases managed expectantly during pregnancy in six tertiary centers from five Latin American countries. The utility of the observed/expected lung‐to‐head ratio (O/E‐LHR) in predicting neonatal survival was assessed, and the best cut‐off to predict prognosis was automatically selected by decision tree analysis.

Results

A total of 99 right sided CDH cases were recruited, 58 isolated fetuses were selected at a median gestational age of 26.2 weeks, showing an overall survival rate of 26.2%. A linear trend was observed between survival and the O/E‐LHR, showing that at higher O/E‐LHR, the greater probability of survival (r = 0.56, p < 0.001). O/E‐LHR discriminates two groups with different survival outcomes: fetuses with an O/E‐LHR ≥65% showed a significantly higher survival rate than those with an O/E‐LHR <65% (81.8% vs. 15.6%, p < 0.01).

Conclusions

Overall survival rate in right sided CDH is lower in Latin American countries. The severity category of pulmonary hypoplasia should be classified according to lung area and the survival rate in such population.
Examining the sustainable development approach of migrants' remittances and financial development in sub‐Saharan African countries
Authors: Kacou Kacou Yves Thierry , Kassouri Yacouba , Alola Andrew Adewale , Altuntaş Mehmet
Published: December 2021

In achieving a desirable sustainable economic growth in developing countries, the role of financial development and international migrant remittances cannot be underplayed. This study attempts to investigate the dynamic interactions between the migrant remittances and the financial sector development from a multidimensional perspective in 22 sub‐Sahara African countries using a panel vector autoregression model over the period 2004–2017. Specifically, the study focuses on the multidimensions of financial development including financial depth, financial access, and financial efficiency in financial institutions (FI) and their relationship with the remittances. The findings suggest that: First, the migrant's remittances are detrimental for the overall FI while the FI are found to positively influence the remittances inflows. Second, the relationship between the remittances and the FI varies with the dimensions of FI. There is a positive dynamic interaction between the remittances, the financial efficiency, and financial access, except for the financial depth. The analysis in this investigation offers relevant policy directives especially on the role of remittances in building stable FI of the sub‐Saharan African economies and other developing states.
High Inhibition of Bentonite Hydration by Use of a Homopolymer Containing Synergistic Bi‐Functional Groups
Authors: Wang Hao , Gao Yihang
Published: December 2021

Most current inhibitors control bentonite hydration at the partial phase by the single adsorption mode. To improve inhibition and action range, we synthesized a novel homopolymer inhibitor (PIM‐NH2) containing bi‐functional groups. Comprehensive experiments investigated the inhibition of PIM‐NH2and other inhibitors. In immersion and linear expansion experiments, the hydration swelling of bentonite cake was incredibly restrained in 0.75 % PIM‐NH2solution. The greater contact angle between 0.75 % PIM‐NH2solution and bentonite cake indicated the retardation of water invasion. According to XRD analysis, the intercalation of 0.75 % PIM‐NH2reduced the bentonite lattice spacing from 1.91 nm to 1.27 nm with water discharge. All results suggested PIM‐NH2had an outstanding performance at the lower concentration, and its inhibition covered the whole hydration process. Mechanism investigation revealed two synergistic adsorptions (hydrogen bond and electrostatic attraction) of bi‐functional groups exerted simultaneously to improve each other. In FT‐IR spectra, the hydrogen bond was confirmed by the special frequency movement from 1550 cm−1to 1641 cm−1.The electrostatic attraction decreased the ζ potential absolute value from 29.55–33.20 mV to around 4 mV. In ESEM analysis, the bentonite treated by 0.75 % PIM‐NH2showed larger aggregates and rough surfaces, demonstrating dehydration properties.
Nano SiO2 Catalyzed Chemo‐Selective Synthesis of N′‐Benzylidene‐2‐cyano‐2‐(10‐oxophenanthren‐9(10H)‐ylidene) or (2‐Oxoindolin‐3‐ylidene)acetohydrazide Derivatives
Authors: Hosseini Hajar , Bayat Mohammad
Published: December 2021

Two new categories of Michael acceptors: N′‐benzylidene‐2‐cyano‐2‐oxophenanthren acetohydrazides and N′‐benzylidene‐2‐cyano‐2‐oxoindolin acetohydrazides, have been successfully synthesized via a one‐pot three‐component reaction using cyanoacetohydrazide, aromatic aldehydes and 9,10‐phenanthroquinone or isatin in a mixture of water and ethanol in the presence of nano sized SiO2 as a heterogeneous catalyst at reflux conditions. The new efficient approach involves two chemo‐selective sequences of hydrazone formation and Knoevenagel condensation. The benefits of this process include availability of starting compounds, simplicity of operation and work‐up procedure, good to excellent yields, the use of green solvents and high chemo‐selectivity of products.
Synthesis of Pyrazoles through [3+2] Cyclization of Nitrile Imines with Cinnamaldehydes Followed by Air Oxidation
Authors: Gao Limei , Shi Ruijie , Tian Yuting , Luo Xi , Zheng Yongsheng , Wang Qiang
Published: December 2021

An unprecedented [3+2] cycloaddition reaction of in situ generated nitrile imines with cinnamyl aldehydes followed by air oxidation has been successfully developed under mild conditions, providing an efficient approach to multisubstituted pyrazoles (up to 88 % yield). Preliminary mechanistic investigation implies that the final product is generated through oxidation in the presence of air. The prominent features of this reaction include mild conditions, simple operation and gram‐scale synthesis.
Organophosphoric Acid Promoted Transamidation: Using N,N‐Dimethylformamide and N,N‐Dimethylacetamide as the Acyl Sources
Authors: Jiang Jian , Li Linlin , Zhang Ling , Chen Qian , Sun Hao , Liao Shanggao , Li Chun , Zhang Lin
Published: December 2021

A new and efficient protocol for the transamidation promoted by organophosphoric acid has been reported. The protocol was applied for the N‐formylation of amines including aromatic, aliphatic and heterocyclic amines, affording moderate to excellent yields (54‐98 %) via the transamidation of N,N‐dimethylformamide (DMF). Similarly, the protocol was used for the N‐acylation of a range of amines, moderate yields via transamidation of N,N‐dimethylacetamide (DMA) were obtained. Moreover, the protocol could be easily performed on a multigram scale.
Redirecting Chemotherapeutics to the Endoplasmic Reticulum Increases Tumor Immunogenicity and Potentiates Anti‐PD‐L1 Therapy
Authors: Xiang Yucheng , Chen Liqiang , Liu Chendong , Yi Xiaoli , Li Lian , Huang Yuan
Published: December 2021

The endoplasmic reticulum (ER) in cancer cells has been considered as a pharmacological target. Still, the effects of a ER‐targeted system remain less investigated, due to the fact that most chemo‐drugs take actions in the nucleus. Here, it is demonstrated that ER‐targeted delivery of doxorubicin (DOX), a typically nucleus‐tropic‐and‐acting agent, attenuates its original effect on cytotoxicity while generating new functions favorable for immune activation. First, a library of DOX derivatives with variable ER‐targeting abilities is synthesized. The results reveal that higher ER‐targeting efficiency correlates with greater ER stress. As compared with naïve drug, ER‐targeted DOX considerably alters the mode of action from nuclear DNA damage‐associated cytotoxicity to ER stress‐mediated calreticulin exposure. Consequently, ER‐targeted DOX decreases cytotoxicity but increases the capability to induce immunogenic cell death (ICD). Therefore, a platform combining naïve and ER‐targeted DOX is constructed for in vivo application. Conventional polymer‐DOX conjugate inhibits tumor growth by exerting a direct killing effect, and ER‐targeted polymer‐DOX conjugate suppresses residual tumors by eliciting ICD‐associated immunity, together resulting in considerable tumor regression. In addition, simultaneous inhibition of adaptive PD‐L1 enrichment (due to negative‐feedback to ICD induction) further leads to greater therapeutic outcome. Collectively, ER‐targeted therapy can enhance anticancer efficacy by promoting ICD‐associated immunotherapy, and potentiating chemotherapy and checkpoint blockade therapy.
Cochineal Dye Concentration and Treatment Time for Otolith Marking of Japanese Smelt Hypomesus nipponensis Embryos
Authors: Miyamoto Kouta , Hoshikawa Hiroki , Nagura Jun , Sawamoto Yoshihiro , Đorđević Miloš , Ohta Kengo
Published: December 2021

The main purpose of this study was to find the optimal cochineal dye concentration and treatment time for marking Japanese smelt (also known as Wakasagi) Hypomesus nipponensis, more specifically their eggs, by understanding the mechanisms that determine survival rates and mark quality. Eggs were immersed in a range of cochineal dye concentrations (40–100 g/L) at varying intervals (6–72 h). Following that, mark quality was evaluated according to fluorescence intensity by examining the marked otolith of the larvae. The statistical model selection indicated that the interaction between the cochineal dye concentrations and immersion intervals (g/L × h) had a negative effect on survival such that at low concentrations survival decreased with increasing immersion time but at high concentrations survival was relatively low at all of the immersion times. On the other hand, the results of evaluating the marked otoliths indicated that mark quality improved with increases in concentration and immersion time individually. These results suggest that there is a trade‐off between mark quality and survival of Japanese smelt when using a cochineal dye solution. Combining the results of the survival rate and mark‐quality experiments, the cochineal dye marking conditions with both high survival rates and high fluorescence intensity are 60 g/L for 24 h, 40 g/L for 48 h, and 40 g/L for 36 h.