bluuebunny/crossref_metadata_2025 huggingface dataset:
microRNA‐related single‐nucleotide polymorphisms and breast cancer
Authors: Bahreini Farbod , Rayzan Elham , Rezaei Nima
Published: July 2020

Breast cancer, as the most common cancer in women which affects patients both mentally and physically, requires great attention in many areas and many levels as this cancer is known to be multifactorial. Single‐stranded molecules called microRNAs with near 22 nucleotides are seen to act in central dogma of molecular biology by inhibiting the translation process; it is demonstrated that any alteration in their sequence especially single‐nucleotide polymorphisms (SNPs) may lead into increasing the breast cancer risk. miR‐SNPs are considered to be the potential biomarkers for early detection of breast cancer. As a result, this review documents the well‐known miR‐SNPs that are known to be associated with breast cancer. In this regard, two principals were discussed: (a) SNPs in the target genes of microRNAs and the alteration in gene expression due to this phenomenon; (b) changes based on the SNPs in the microRNA coding region and the impact on their interaction with target messenger RNA.
Validity and Reproducibility of the ADNEX MR Scoring System in the Diagnosis of Sonographically Indeterminate Adnexal Masses
Authors: Basha Mohammad Abd Alkhalik , Abdelrahman Hossam M. , Metwally Maha Ibrahime , Alayouty Nader Ali , Mohey Nesreen , Zaitoun Mohamed M.A. , Almassry Hosam Nabil , Yousef Hala Y. , El Sammak Ahmed A. , Aly Sameh Abdelaziz , Algazzar Hesham Youssef , Farag Mohamed Abd El‐Aziz Mohamed , Mosallam Walid , Abo Shanab Waleed S. , Ibrahim Safaa A. , Mohamed Ekramy A. , Mohamed Abd El Motaleb , Afifi Amira Hamed Mohamed , Harb Ola A. , Azmy Taghreed M.
Published: July 2020

Background

The diagnosis of sonographically indeterminate adnexal masses (AM) signifies a major challenge in clinical practice. Early detection and characterization have increased the need for accurate imaging evaluation before treatment.

Purpose

To assess the validity and reproducibility of the ADNEX MR Scoring system in the diagnosis of sonographically indeterminate AM.

Study Type

A prospective multicenter study.

Population

In all, 531 women (mean age, 44 ± 11.2 years; range, 21–79 years) with 572 sonographically indeterminate AM.

Field Strength/Sequence

1.5T/precontrast T1‐weighted imaging (WI) fast spin echo (FSE) (in‐phase and out‐of‐phase, with and without fat suppression); T2‐WI FSE; diffusion‐WI single‐shot echo planner with b‐values of 0 and 1000 s/mm2; and dynamic contrast‐enhanced perfusion T1‐WI liver acquisition with volume acceleration (LAVA).

Assessment

All MRI examinations were evaluated by three radiologists, and the AM were categorized into five scores based on the ADNEX MR Scoring system. Score 1: no AM; 2: benign AM; 3: probably benign AM; 4: indeterminate AM; 5: probably malignant AM. Histopathology and imaging follow‐up were used as the standard references for evaluating the validity of the ADNEX MR Scoring system for detecting ovarian malignancy.

Statistical Tests

Four‐fold table test, kappa statistics (κ), and receiver operating characteristic (ROC) curve.

Results

In all, 136 (23.8%) AM were malignant, and 436 (76.2%) were benign. Of the 350 AM classified as score 2, one (0.3%) was malignant; of the 62 AM classified as score 3, six (9.7%) were malignant; of the 73 AM classified as score 4, 43 (58.9%) were malignant; and of the 87 AM categorized as score 5, 86 (98.9%) were malignant. The best cutoff value for predicting malignant AM was score >3 with sensitivity and specificity of 92.9% and 94.9%, respectively. The interreader agreement of the ADNEX MR Scoring was very good (κ = 0.861).

Data Conclusion

The current study supports the high validity and reproducibility of the ADNEX MR Scoring system for the diagnosis of sonographically indeterminate AM.

Level of Evidence

1

Technical Efficacy Stage

2
Spatial segmentation and metabolite annotation involved in sperm maturation in the rat epididymis by MALDI imaging mass spectrometry
Authors: Lagarrigue Mélanie , Lavigne Régis , Guével Blandine , Palmer Andrew , Rondel Karine , Guillot Laetitia , Kobarg Jan H. , Trede Dennis , Pineau Charles
Published: July 2020

Spermatozoa acquire their fertilizing capacity during a complex maturation process that occurs in the epididymis. This process involves a substantial molecular remodeling at the surface of the gamete. Epididymis is divided into three regions (the caput, corpus, and cauda) or into 19 intraregional segments based on histology. Most studies carried out on epididymal maturation have been performed on sperm samples or tissue extracts. Here, we used MALDI imaging mass spectrometry in the positive and negative ion modes combined with spatial segmentation and automated metabolite annotation to study the precise localization of metabolites directly in the rat epididymis. The spatial segmentation revealed that the rat epididymis could be divided into several molecular clusters different from the 19 intraregional segments. The discriminative m/z values that contributed the most to each molecular cluster were then annotated and corresponded mainly to phosphatidylcholines, sphingolipids, glycerophosphates, triacylglycerols, plasmalogens, phosphatidylethanolamines, and lysophosphatidylcholines. A substantial remodeling of lipid composition during epididymal maturation was observed. It was characterized in particular by an increase in the number of sphingolipids and plasmalogens and a decrease in the proportion of triacylglycerols annotated from caput to cauda. Ion images reveal that molecules belonging to the same family can have very different localizations along the epididymis. For some of them, annotation was confirmed by on‐tissue MS/MS experiments. A 3D model of the epididymis head was reconstructed from 61 sections analyzed with a lateral resolution of 50 μm and can be used to obtain information on the localization of a given analyte in the whole volume of the tissue.
Effects of in vivo cyclic compressive loading on the distribution of local Col2 and superficial lubricin in rat knee cartilage
Authors: Ji Xiang , Ito Akira , Nakahata Akihiro , Nishitani Kohei , Kuroki Hiroshi , Aoyama Tomoki
Published: July 2020

This study aimed to examine the effects of an episode of in vivo cyclic loading on rat knee articular cartilage (AC) under medium‐term observation, while also investigating relevant factors associated with the progression of post‐traumatic osteoarthritis (PTOA). Twelve‐week‐old Wistar rats underwent one episode comprising 60 cycles of 20 N or 50 N dynamic compression on the right knee joint. Spatiotemporal changes in the AC after loading were evaluated using histology and immunohistochemistry at 3 days and 1, 2, 4, and 8 weeks after loading (n = 6 for each condition). Chondrocyte vitality was assessed at 1, 3, 6, and 12 hours after loading (n = 2 for each condition). A localized AC lesion on the lateral femoral condyle was confirmed in all subjects. The surface and intermediate cartilage in the affected area degenerated after loading, but the calcified cartilage remained intact. Expression of type II collagen in the lesion cartilage was upregulated after loading, whereas the superficial lubricin layer was eroded in response to cyclic compression. However, the distribution of superficial lubricin gradually recovered to the normal level 4 weeks after loading‐induced injury. We confirmed that 60 repetitions of cyclic loading exceeding 20 N could result in cartilage damage in the rat knee. Endogenous repairs in well‐structured joints work well to rebuild protective layers on the lesion cartilage surface, which may be the latent factor delaying the progression of PTOA.
The vertical course of bone regeneration in maxillary sinus floor augmentations: A histomorphometric analysis of human biopsies
Authors: Beck Florian , Reich Karoline Maria , Lettner Stefan , Heimel Patrick , Tangl Stefan , Redl Heinz , Ulm Christian
Published: July 2020

Background

Maxillary sinus floor augmentation (MSFA) is a well‐established and predictable augmentation method in severely resorbed maxillae. However, data on the vertical course of bone graft consolidation within the maxillary sinus are rare. The aim of the present study was to quantify the vertical distribution of new bone formation (nBF) in MSFA and to characterize the vertical gradient of bone graft consolidation.

Methods

Eighty‐five human sinus biopsies were harvested 6 ± 1 months after MSFA. Histological thin‐ground sections were prepared and histomorphometrically analyzed. The volume of newly formed bone (nBV/TV) was measured in serial zones of 100 μm proceeding from the bottom of the sinus floor (SF) up to the apical top of the biopsy. The gradient of nBV/TV within the augmentation area was determined by the vertical distribution of nBV/TV along these zones.

Results

In the premolar region, nBV/TV slightly declined from 20.4% in the zone adjacent to the SF to 17.7% at a distance of 8 mm. The gradient was steeper in the molar region: nBV/TV decreased from 18.7% to 12.8%. This decline was even more distinct when the volume fraction and the height of the residual bone of the SF were low.

Conclusions

nBF follows a gradient from native bone of the SF towards the apical part of the augmentation area. The distance to primordial bone thus plays a critical role for bone regeneration in MSFA, particularly in the molar region.
Association between low bone mineral density and periodontitis in generally healthy perimenopausal women
Authors: Gil‐Montoya José Antonio , Garrido‐Martínez Macarena , Barrios‐Rodríguez Rocío , Ramos‐García Pablo , Lenouvel Daniel , Montes‐Castillo Cristina , Martínez‐Ramírez María José
Published: July 2020

Background

The association between low bone mineral density (BMD) and periodontitis in perimenopausal women is controversial. The purpose of this study was to determine whether osteoporosis or osteopenia is associated with periodontal disease in a population of adult women.

Methods

A sample of over‐45‐year‐old women with or without low BMD underwent lumbar spine and hip bone densitometry and a complete periodontal examination. The extent/severity or absence of periodontal disease was noted using two different case definitions. Data were gathered on socio‐economic status, medication history, systemic co‐morbidities, alcohol or tobacco use as well as serum levels of calcium and vitamin D.

Results

One hundred seventy three women aged between 45 and 72 years old were recruited with a mean age of 57.8 years. One hundred and three had decreased BMD (61 with osteoporosis and 42 with osteopenia) and 70 were healthy. Moderate or severe periodontitis was present in 52.6% of the women. Multivariate analysis showed a clear association between low BMD and periodontitis, but only in women above 58 years old and independent of tobacco consumption or oral hygiene.

Conclusion

In this sample of generally healthy perimenopausal women, low BMD was associated with clinical attachment level (CAL). Women over 58 years old with decreased BMD presented with a higher mean percentage of sites with CAL ≥ 4 mm as well as CAL ≥ 6 mm when compared to controls, independent of active smoking status or poor oral hygiene.
Influence of psychological stress on non‐surgical periodontal treatment outcomes in patients with severe chronic periodontitis
Authors: Petit Catherine , Anadon‐Rosinach Victor , Rettig Laurence , Schmidt‐Mutter Catherine , Tuzin Nicolas , Davideau Jean‐Luc , Huck Olivier
Published: July 2020

Background

The aim of this study was to evaluate the influence of psychological stress on non‐surgical periodontal treatment (SRP) outcomes in patients with severe chronic periodontitis (stage 3/4 generalized periodontitis) at 6 months in the French population.

Methods

Patients diagnosed with severe generalized chronic periodontitis (periodontitis stage 3/4) were included in this study. At baseline, psychological status was evaluated by self‐administered questionnaire (Depression Anxiety Stress Scale 42 [DASS‐42] and Toulouse coping scale [TCS]). Plasma levels of cortisol and chromogranin‐A were determined. Patients were then managed by oral hygiene instructions, scaling and root planing of sites with PD >3 mm and followed at 3 and 6 months. Quantitative and qualitative variables were described and interactions were determined by linear and logistic regressions.

Results

Seventy‐one patients were included in this study and 54 were followed up to 6 months. An average probing depth (PD) reduction of 0.73 ± 0.11 mm and decrease of diseased sites (PD >3 mm) were measured at 6 months illustrating SRP efficacy. Multivariable analysis showed that increased DASS‐stress score was associated to worsened SRP outcomes in terms of bleeding on probing (BOP) (OR = 1.02, P <0.05) and mean PD (P <0.05) reduction. An increase of DASS‐depression score negatively influenced PD >5 mm (OR = 1.06, P <0.05), PD >7 mm (OR = 1.17, P <0.01), CAL >5 mm (OR = 1.03, P <0.05), and CAL >7 mm (OR = 1.07, P <0.05) reduction. Negative coping strategies were also associated with worsened SRP outcomes.

Conclusions

Patients with increased stress, anxiety, and depression scores as well as those exhibiting negative coping strategies demonstrate worsened SRP outcomes. DASS‐42 and TCS were useful to determine psychological status and their use could be incorporated to assess treatment prognosis.
Outpatient management of deep vein thrombosis using direct oral anticoagulants is safe and efficient
Authors: Lim Hui Yin , Lambros Pani , Krishnamoorthi Brintha , Chellaram Vinod , Ho Prahlad W.
Published: July 2020

Direct oral anticoagulants (DOACs) are increasingly becoming the treatment of choice for venous thromboembolism (VTE). To ensure safe prescription and prevent delay of supply for dischargeable patients with deep venous thrombosis (DVT) presenting to the Emergency Department (ED) outside pharmacy hours, we implemented a “Rivaroxaban after‐hours pack” system, that requires prescribers to assess suitability via criteria detailed in a decision support system GuidanceMS, prior to pack provision. Pharmacist and clinic follow up is also provided. To assess the safety and effectiveness of the program, a retrospective case series review was undertaken of DVT patients discharged from the ED with an after‐hours pack from April 2015 to December 2017. Patients were assessed for compliance with recommendations for treatment from their baseline demographics, biochemistry, medication history, bleeding and thrombotic risk. Any bleeding episodes or clot extension were recorded. The number of admissions for hospital DVT treatment for the study period was compared to the preceding 30 months. Of the 120 patients reviewed, all patients had adequate renal function, 96.3% had liver function tests <3× the upper limit normal. Three patients (2.5%) had active malignancy and no patients had a mechanical valve or antiphospholipid syndrome. All patients received a pharmacist telephone follow‐up education conversation and referral to Thrombosis Outpatients. Twelve patients reported clinically relevant non‐major bleeding, while two patients had clot extension despite compliance. There was marked reduction in hospital and/or hospital‐in‐the‐home admissions compared to the previous 30 months (P < 0.001). In conclusion, all DVT patients were safely prescribed Rivaroxaban using this system, with a reduction in hospital and/or hospital‐in‐the‐home admissions. This system is efficient in ensuring safe provision of Rivaroxaban outside of pharmacy hours, with potential for extension to the primary care setting.
Effects of suppressing bioavailability of insulin‐like growth factor on age‐associated intervertebral disc degeneration
Authors: Kritschil Rebecca , Zhang Zhongying , Lei Changbin , Zhong Jiongbiao , Dong Qing , Lee Joon , Conover Cheryl A. , Sowa Gwendolyn , Vallejo Abbe N. , Vo Nam
Published: July 2020

Suppression of the insulin‐like growth factor‐1 (IGF‐1) signaling pathway reduces age‐related disorders and increases lifespan across species, making the IGF‐1 pathway a key regulator of aging. Previous in vitro intervertebral disc cell studies have reported the pro‐anabolic effect of exogenously adding IGF‐1 on matrix production. However, the overall effects of suppressing IGF‐1 signaling on age‐related intervertebral disc degeneration (IDD) is not known. Here, the effects of suppressing IGF‐1 signaling on age‐related IDD in vivo were examined using PAPPA−/− mice. These are animals with targeted deletion of pregnancy‐associated plasma protein A (PAPPA), the major protease that cleaves inhibitory IGF binding proteins that control bioavailability of IGF‐1 for cell signaling. Compared to age‐matched wild‐type (Wt) littermates, reduced levels of matrix proteoglycan (PG) and aggrecan were seen in discs of 23‐month old PAPPA−/− mice. Decreased aggrecanolysis and expression of two key catabolic markers, matrix metalloproteinase‐3 and a disintegrin and metalloproteinase with thrombospondin motifs‐4, were also observed in discs of old PAPPA−/− mice compared to Wt littermates. Suppressing IGF‐1 signaling has been implicated to shift cellular metabolism toward maintenance rather than growth and decreasing cellular senescence. Along this line, discs of old PAPPA−/− mice also exhibited lower cellular senescence, assessed by p53 and lamin B1 markers. Collectively, the data reveal complex regulation of disc matrix homeostasis by PAPPA/IGF‐1 signaling during chronologic aging, that is, reduced IGF‐1 bioavailability confers the benefit of decreasing disc cellular senescence and matrix catabolism but also the disadvantage of decreasing disc PG matrix anabolism. This pathway requires further mechanistic elucidation before IGF‐1 could be considered as a therapeutic growth factor for treating IDD.
Local food consumption during travel: Interaction of ıncentive‐disincentive factors, togetherness, and hedonic value
Authors: Dedeoğlu Bekir Bora , Çalışkan Caner , Sabbağ Çiğdem
Published: July 2020

This study addresses the local food consumption experience as it takes place while traveling. The mediating effects of incentive (novelty) and disincentive (risk avoidance, familiarity) factors, sense of togetherness, and hedonic value, and their effect on the travel experience, were investigated. The study also considered the moderating effect of gender. The data showed a significant relationship between togetherness and hedonic value. Perceptions of novelty were shown to affect togetherness positively. Furthermore, the effect of risk avoidance on togetherness was found to be more determinative for male respondents, whereas the effect of familiarity on togetherness was more determinative for female respondents.
The Effects of Laryngoscope Shape and Needle Position on Distal Airway Pressure in Jet Ventilation
Authors: Pertile Joshua , Mellenthin Michelle , Wagner Jennifer , DeBoer Emily M. , Fink Daniel , Smith Bradford
Published: July 2020

Objectives

Laryngoscopes and subglottiscopes of multiple shapes and lengths are used in airway surgery to maintain an open airway; protect the trachea; and provide a place to mount the light, evacuator, and ventilation needle. Despite differences in scopes and ventilation needle mounting positions, the same jet pressures are typically used. We hypothesized that different scopes and scope configurations would affect distal airway pressure magnitude and homogeneity.

Study Design

A laboratory investigation of distal airway pressures in a lung modelduring low frequency jet ventilation.

Methods

A three‐dimensional airway model based on the computed tomography scan of a 15‐year old healthy male was fabricated with pressure transducers at the fifth airway generation. A laryngoscope and a subglottiscope were each mounted in the model coaxial with the trachea. Parameters including scope depth and needle mounting position were adjusted, and the effects on distal airway pressure were recorded.

Results

Changing the scope depth from 1 to 3 cm past the laryngeal inlet had a limited effect on distal airway pressure. Needle mounting angle in the laryngoscope strongly influenced distal airway pressure, with a 7° angle change yielding a 67.5% increase. Compared to a loose needle centered in the trachea 1 cm past the laryngeal inlet, the subglottiscope and laryngoscope showed up to 16% and 150% increases in distal airway pressure, respectively.

Conclusion

Different scopes or changes in the configuration, such as the needle angle, strongly influence distal airway pressure. Our findings indicate that different jet pressures are required for different scopes and that a stable needle mount is a critical design consideration to prevent changes in minute ventilation due to needle movement.

Level of Evidence

NA (Basic Research) Laryngoscope, 131:E354–E357, 2021
Nasal Endoscopy During the COVID‐19 Pandemic: Mitigating Risk with 3D Printed Masks
Authors: Davies Joel C. , Chan Harley H. L. , Gilbert Ralph W. , Irish Jonathan C.
Published: July 2020

View Video S1
Optimum Naso‐oropharyngeal Swab Procedure for COVID‐19: Step‐by‐Step Preparation and Technical Hints
Authors: Coden Elisa , Russo Federico , Arosio Alberto D. , Castelnuovo Paolo , Karligkiotis Apostolos , Volpi Luca
Published: July 2020

View Video S1
Toward Chiral Sensing and Spectroscopy Enabled by All‐Dielectric Integrated Photonic Waveguides
Authors: Vázquez‐Lozano J. Enrique , Martínez Alejandro
Published: July 2020

Chiral spectroscopy is a powerful technique enabling to identify optically the chirality of matter. So far, most experiments to check the chirality of matter or nanostructures have been performed through arrangements wherein both the optical excitation and detection are realized via circularly polarized light propagating in free space. However, for the sake of miniaturization, it would be desirable to perform chiral spectroscopy in photonic integrated platforms, with the additional benefit of massive parallel detection, low‐cost production, repeatability, and portability. Here it is shown that all‐dielectric photonic waveguides can support chiral modes under proper combination of fundamental eigenmodes. Two mainstream configurations are investigated: a dielectric wire with square cross section and a slotted waveguide. Three different scenarios in which such waveguides could be used for chiral detection are numerically analyzed: waveguides as near‐field probes, evanescent‐induced chiral fields, and chiroptical interaction in void slots. In all the cases, a metallic nanohelix is considered as a chiral probe, though all the approaches can be extended to other kinds of chiral nanostructures as well as matter. These results establish that chiral applications such as sensing and spectroscopy could be realized in standard integrated optics, in particular, with silicon‐based technology.
Sequence‐Defined Heteromultivalent Precision Glycomacromolecules Bearing Sulfonated/Sulfated Nonglycosidic Moieties Preferentially Bind Galectin‐3 and Delay Wound Healing of a Galectin‐3 Positive Tumor Cell Line in an In Vitro Wound Scratch Assay
Authors: Freichel Tanja , Heine Viktoria , Laaf Dominic , Mackintosh Eleanor E. , Sarafova Sophia , Elling Lothar , Snyder Nicole L. , Hartmann Laura
Published: July 2020

Within this work, a new class of sequence‐defined heteromultivalent glycomacromolecules bearing lactose residues and nonglycosidic motifs for probing glycoconjugate recognition in carbohydrate recognition domain (CRD) of galectin‐3 is presented. Galectins, a family of β‐galactoside‐binding proteins, are known to play crucial roles in different signaling pathways involved in tumor biology. Thus, research has focused on the design and synthesis of galectin‐targeting ligands for use as diagnostic markers or potential therapeutics. Heteromultivalent precision glycomacromolecules have the potential to serve as ligands for galectins. In this work, multivalency and the introduction of nonglycosidic motifs bearing either neutral, amine, or sulfonated/sulfated groups are used to better understand binding in the galectin‐3 CRD. Enzyme‐linked immunosorbent assays and surface plasmon resonance studies are performed, revealing a positive impact of the sulfonated/sulfated nonglycosidic motifs on galectin‐3 binding but not on galectin‐1 binding. Selected compounds are then tested with galectin‐3 positive MCF 7 breast cancer cells using an in vitro would scratch assay. Preliminary results demonstrate a differential biological effect on MCF 7 cells with high galectin‐3 expression in comparison to an HEK 293 control with low galectin‐3 expression, indicating the potential for sulfonated/sulfated heteromultivalent glycomacromolecules to serve as preferential ligands for galectin‐3 targeting.
Lacrimo‐auriculo‐dento‐digital syndrome: A novel mutation in a Korean family and review of literature
Authors: Ryu Young Hye , Kyun Chae Jong , Kim Jung‐Wook , Lee Soyoung
Published: July 2020

Background

Lacrimo‐auriculo‐dento‐digital (LADD) syndrome is a rare autosomal dominant disorder caused by mutations in one of the three genes: fibroblast growth factor receptor 2 (FGFR2), FGFR3, or FGF10. Affected patients have hypoplasia/aplasia of lacrimal ducts/glands, hypoplasia/aplasia of salivary glands, dental anomalies, ear anomalies, hearing loss, and digital anomalies.

Case Presentation

Proband was an 11‐year‐old male with xerostomia, xerophthalmia, and a referring diagnosis of Sjogren syndrome. He presented with microdontia, hypodontia, low‐set/cupped ear auricles, and hearing loss in the left ear.

Methods

Whole exome sequencing (WES) was performed on proband. Variations and segregation within the family were verified using Sanger sequencing.

Results

Molecular studies revealed a novel heterozygous missense mutation in exon 11 of FGFR2: c.1547C>T (p.Ala516Val), compatible with LADD syndrome.

Conclusion

To the best of our knowledge, this is the first report of a family with LADD syndrome in Korea. The combination of xerostomia and xerophthalmia, seen in patients with LADD syndrome, may be misdiagnosed as Sjogren syndrome. WES may be a useful clinical tool in ascertaining the affected gene in patients with suspected genetic disorders. Here, a literature review and summary of 23 case reports/series of LADD syndrome are presented, which may help to identify patients with this condition.
Whole genome sequencing identifies a duplicated region encompassing Xq13.2q13.3 in a large Iranian family with intellectual disability
Authors: Mehvari Sepideh , Larti Farzaneh , Hu Hao , Fattahi Zohreh , Beheshtian Maryam , Abedini Seyedeh Sedigheh , Arzhangi Sanaz , Ropers Hans‐Hilger , Kalscheuer Vera M. , Auld Daniel , Kahrizi Kimia , Riazalhosseini Yasser , Najmabadi Hossein
Published: July 2020

Background

The X chromosome has historically been one of the most thoroughly investigated chromosomes regarding intellectual disability (ID), whose etiology is attributed to many factors including copy number variations (CNVs). Duplications of the long arm of the X chromosome have been reported in patients with ID, short stature, facial anomalies, and in many cases hypoplastic genitalia and/or behavioral abnormalities.

Methods

Here, we report on a large Iranian family with X‐linked ID caused by a duplication on the X chromosome identified by whole genome sequencing in combination with linkage analysis.

Results

Seven affected males in different branches of the family presented with ID, short stature, seizures, facial anomalies, behavioral abnormalities (aggressiveness, self‐injury, anxiety, impaired social interactions, and shyness), speech impairment, and micropenis. The duplication of the region Xq13.2q13.3, which is ~1.8 Mb in size, includes seven protein‐coding OMIM genes. Three of these genes, namely SLC16A2, RLIM, and NEXMIF, if impaired, can lead to syndromes presenting with ID. Of note, this duplicated region was located within a linkage interval with a LOD score >3.

Conclusion

Our report indicates that CNVs should be considered in multi‐affected families where no candidate gene defect has been identified in sequencing data analysis.
Lyapunov functions for random semi‐dynamical systems in terms of tempered exponential splitting
Authors: Popa Ioan‐Lucian
Published: July 2020

For a general one‐sided random dynamical system, we consider the notion of tempered exponential splitting with respect to invariant projectors, and we characterize it in terms of Lyapunov functions. Moreover, we establish counterpart results for tempered exponential dichotomy with respect to strongly invariant projections.
Loss of Uncoupling Protein 3 Attenuates Western Diet–Induced Obesity, Systemic Inflammation, and Insulin Resistance in Rats
Authors: Lomax Tyler M. , Ashraf Sadia , Yilmaz Gizem , Harmancey Romain
Published: July 2020

Objective

Uncoupling protein 3 (UCP3) is a mitochondrial carrier related to fatty acid metabolism. Although gene variants of UCP3 are associated with human obesity, their contribution to increased adiposity remains unclear. This study investigated the impact that loss of UCP3 has on diet‐induced obesity in rats.

Methods

Male UCP3 knockout rats (ucp3−/−) and wild‐type littermates (ucp3+/+) were fed a high‐fat, high‐carbohydrate Western diet for 21 weeks. Body composition was analyzed by EchoMRI. Whole‐body insulin sensitivity and rates of tissue glucose uptake were determined by using hyperinsulinemic‐euglycemic clamp. Changes in tissue physiology were interrogated by microscopy and RNA sequencing.

Results

Loss of UCP3 decreased fat mass gain, white adipocytes size, and systemic inflammation. The ucp3−/− rats also exhibited preserved insulin sensitivity and increased glucose uptake in interscapular brown adipose tissue (iBAT). Brown adipocytes from ucp3−/− rats were protected from cellular degeneration caused by lipid accumulation and from reactive oxygen species–induced protein sulfonation. Increased glutathione levels in iBAT from ucp3−/− rats were linked to upregulation of genes encoding enzymes from the transsulfuration pathway in that tissue.

Conclusions

Loss of UCP3 partially protects rats from diet‐induced obesity. This phenotype is related to induction of a compensatory antioxidant mechanism and prevention of iBAT whitening.

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Stock market liquidity: Implication of local and global investor sentiment
Authors: Debata Byomakesh , Dash Saumya Ranjan , Mahakud Jitendra
Published: July 2020

This article examines the impact of local and global investor sentiment on stock market liquidity using data from an order‐driven emerging market. Along with four different liquidity proxies, the empirical analysis uses one domestic investor sentiment index and four global sentiment proxies that represent investor sentiment of United States, Europe, and aggregate emerging market sentiment. Granger‐causality test results suggest that investor sentiment significantly Granger‐causes stock market liquidity. We also find that investor sentiment is an essential determinant of stock market liquidity and the impact of global investor sentiment persists even after controlling local sentiment. The empirical findings are robust across different sample periods and liquidity measures.
Improved microwave absorbing performance of natural rubber composite with multi‐walled carbon nanotubes and molybdenum disulfide hybrids
Authors: Geng Haoran , Zhao Pengfei , Mei Junfei , Chen Yongping , Yu Rentong , Zhao Yanfang , Ding Aiwu , Peng Zheng , Liao Lusheng , Liao Jianhe
Published: July 2020

Multicomponent nanocomposites demonstrate many properties that are not found in their mono‐counterparts. Here, natural rubber (NR) composites with improved electromagnetic properties were prepared via incorporating hybrids of one‐dimensional multi‐walled carbon nanotubes (MWCNTs) and two‐dimensional molybdenum disulfide (MoS2). Evidenced by the morphological results, the restacking of MoS2 and the tortuous of MWCNTs are effectively inhibited due to the depletion‐effect of the different dimensional nanoblocks. Owing to the synergetic effect of MWCNTs and MoS2, the resulted NR/MWCNTs/MoS2 nanocomposites showed higher electromagnetic properties than their NR/MWCNTs and NR/MoS2 counterparts did. The reflection loss of NR/MWCNTs/MoS2 composites with 5 vol% MWCNTs and 5 vol% MoS2 is −49.04 dB, which is 9.2 and 21.9 times stronger than that of sole MWCNTs or MoS2 filled NR composites, respectively. Such composite with excellent microwave capacity could be used as a new kind of candidate for the new types of microwave absorbing materials.
Biodegradable synthetic polymeric composite scaffold‐based tissue engineered heart valve with minimally invasive transcatheter implantation
Authors: Long Lin‐yu , Wu Can , Hu Xue‐feng , Wang Yun‐bing
Published: July 2020

Prosthetic heart valve replacement is the main treatment for valvular heart disease, but the existing artificial valves (mechanical or biological valve) have inherent disadvantages. Patients with mechanical valves require lifelong anticoagulation because of the high risk of thromboembolism, while the durability of biological valve is poor, which easily leads to calcification or lobular degeneration. Besides, they all lack the abilities of self‐repair and growth which are very important for adolescent patients with valvular heart disease. To overcome these shortcomings, the researchers developed tissue engineered heart valves (TEHV) with self‐repairing and remodeling capabilities, low immunogenicity, and great durability. The preparation of three‐dimensional porous scaffolds is the key step in the success of TEHV. Because of their easy processing, active chemical properties, great mechanical properties and controllable degradation rate, synthetic biodegradable polymers are widely used in the preparation of TEHV scaffolds. This review summarizes the types, properties and process techniques of biodegradable synthetic polymers, such as polycaprolactone, polyglycolic acid, polylactic acid, and polyhydroxyalkanoates currently used to prepare the TEHV scaffolds. This review also focuses on the composite methods and performance of synthetic polymer‐based composite scaffolds. The prospects and challenges of the clinical application for minimally invasive implantation of TEHV are also discussed.
Identification of the distinct genomic features in gastroesophageal junction adenocarcinoma and its Siewert subtypes
Authors: Geng Qirong , Lao Jiawen , Zuo Xiaoyu , Chen Shangxiang , Bei Jin‐Xin , Xu Dazhi
Published: July 2020

Rates of gastroesophageal junction adenocarcinomas (GEJAs) have shown an alarming increase; however, the genetic background of GEJA and its Siewert classification have yet to be uncovered. Here, 60 paired tumor and normal DNA samples from GEJA patients were analyzed by whole‐exome sequencing. Among them, 13 were Siewert type I, 14 were type II, and 33 were type III. A predominance of C/G>T/A substitutions was discovered in GEJA, followed by C/G>A/T substitutions. Notably, Siewert type I and type II/III display distinct sets of driver genes, mutational spectrum, and recurrently disrupted pathways. Siewert type I showed similarity to esophageal adenocarcinomas (EACs) and the chromosomal instability subtype of stomach adenocarcinomas, while Siewert type II/III showed similarity to the genomic stable subtype of stomach adenocarcinoma. We also found that mutation of FBXW7, a driver gene of GEJA, was enriched in Siewert type I. Our data identify differences between GEJA and stomach/EACs at the genomic level and provide evidence for differential treatment based on Siewert classification of GEJA. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Expansion of the renal capsular stroma, ureteric bud branching defects and cryptorchidism in mice with Wilms tumor 1 gene deletion in the stromal compartment of the developing kidney
Authors: Weiss Anna‐Carina , Rivera‐Reyes Reginaldo , Englert Christoph , Kispert Andreas
Published: July 2020

Development of the mammalian kidney is orchestrated by reciprocal interactions of stromal and nephrogenic mesenchymal cells with the ureteric bud epithelium. Previous work showed that the transcription factor Wilms tumor 1 (WT1) acts in the nephrogenic lineage to maintain precursor cells, to drive the epithelial transition of aggregating precursors into a renal vesicle and to specify and maintain the podocyte fate. However, WT1 is expressed not only in the nephrogenic lineage but also transiently in stromal progenitors in the renal cortex. Here we report that specific deletion of Wt1 in the stromal lineage using the Foxd1cre driver line results at birth in cryptorchidism and hypoplastic kidneys that harbour fewer and enlarged ureteric bud tips and display an expansion of capsular stroma into the cortical region. In vivo and ex vivo analysis at earlier stages revealed that stromal loss of Wt1 reduces stromal proliferation, and delays and alters branching morphogenesis, resulting in a variant architecture of the collecting duct tree with an increase of single at the expense of bifurcated ureteric bud tips. Molecular analysis identified a transient reduction of Aldh1a2 expression and of retinoic acid signalling activity in stromal progenitors, and of Ret in ureteric bud tips. Administration of retinoic acid partly rescued the branching defects of mutant kidneys in culture. We propose that WT1 maintains retinoic acid signalling in the cortical stroma, which, in turn, assures proper levels and dynamics of Ret expression in the ureteric bud tips, and thus normal ramification of the ureteric tree. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Height after photon craniospinal irradiation in pediatric patients treated for central nervous system embryonal tumors
Authors: Mizumoto Masashi , Oshiro Yoshiko , Pan Haitao , Wang Fang , Kaste Sue C. , Gajjar Amar , Chemaitilly Wassim , Merchant Thomas E.
Published: July 2020

Background

We modeled height after craniospinal irradiation (CSI) in pediatric patients with central nervous system (CNS) embryonal tumors to identify factors that impair stature.

Procedure

During 1996‐2012, 212 pediatric patients (131 male) with CNS embryonal tumors received postoperative CSI: 23.4 Gy (n = 147) or ≥36 Gy (n = 65), similar postirradiation chemotherapy, and were followed for at least 5 years without tumor progression or other event. The group was further characterized by age at CSI and hormone‐replacement therapy received. Models were developed to identify factors associated with growth impairment and estimate final height.

Results

With median follow up of 10.2 years (range 5.0‐20.4 years), the mean final height z‐scores at 18 years of age, compared to United States standards, were −1.3 for female and −1.5 for male survivors. Younger age at the time of CSI, higher CSI dose, and female sex were associated with height impairment. Factors associated with higher growth rates before 15 years of age were older age at CSI, male sex, CSI dose < 36 Gy, replacement therapy for growth hormone (GH) and central adrenal insufficiency, and white race. Growth after age 15 in male survivors was associated with treatment of gonadotropin deficiency. Linear mixed‐effects models were developed using clinical factors to estimate final height, demonstrate the unique growth curve of this cohort, and interactions between clinical variable and radiation dose.

Conclusions

CSI significantly impaired height at current doses used to treat standard‐ or high‐risk CNS embryonal tumors. Measures to reduce the impact of CSI on height should be sought, with our models serving as benchmarks.
A pharmacist‐managed dosing algorithm for darbepoetin alfa and iron sucrose in hemodialysis patients: A randomized, controlled trial
Authors: van den Oever Francisca Johanna , Heetman‐Meijer Carolien F. M. , Birnie Erwin , Vasbinder Erwin C. , Swart Eleonora L. , Schrama Yvonne C.
Published: July 2020

The attainment of target hemoglobin levels in hemodialysis patients is low. Several factors play a role, such as hyporesponsiveness to erythropoiesis‐stimulating agents (ESA), but also suboptimal prescribing of ESA and iron. The goal of this study was to investigate if a pharmacist‐managed dosing algorithm for darbepoetin alfa (DA) and iron sucrose improves the attainment of target hemoglobin levels. In this randomized controlled trial, 200 hemodialysis patients from a Dutch teaching hospital were included. In the intervention group (n = 100), a pharmacist monthly provided dose recommendations for DA and iron sucrose based on dosing algorithms. The control group (n = 100) received usual care. In the intervention group, the percentage per patient within the target range (PTR) for hemoglobin (target range 6.8‐7.4 mmol/L) and iron status was higher than in the control group (for hemoglobin median 38.5% vs 23.1%, P = .001 and for iron status median 21.1% vs 8.3%, P = .003). The percentage of high hemoglobin levels (>8.1 mmol/L) was lower in the intervention group (median 0.0% vs 7.7%, P = .034). The weekly dose of DA was lower in the intervention group (median 34.0 vs 46.9 mcg, P = .020), whereas iron dose was higher (median 75 vs 0 mg). No difference was found for the percentage of hemoglobin levels below the target range. In conclusion, a pharmacist‐managed dosing algorithm for DA and iron sucrose increased the attainment of target levels for hemoglobin and iron status, reduced the percentage of high hemoglobin levels, and was associated with a lower DA and a higher iron sucrose dose.
Finite‐time fault tolerant control for stochastic parameter systems with intermittent fault under stochastic communication protocol
Authors: Ju Yamei , Wei Guoliang , Ding Derui , Liu Shuai
Published: July 2020

In this article, the finite‐time fault tolerant control problem is investigated for a class of discrete‐time stochastic parameter systems subject to censored measurements. For the sake of relieving the communication burden, a stochastic communication protocol governed by a Markov chain is employed to determine which actuator has the access to the network at each transmission instant. Moreover, an improved performance index dependent on the predetermined censored threshold is constructed to evaluate the disturbance rejection level of the fault tolerant controller in the simultaneous presence of both external disturbances and censoring effects. The main aim of the addressed problem is to design a fault tolerant controller such that the closed‐loop system satisfies both the stochastically finite‐time boundedness and H∞ performance requirements. In light of the Lyapunov theory combined with matrix inequalities, some sufficient conditions are derived skillfully, and the desired controller gains are calculated by solving a set of linear matrix inequalities. Finally, two simulation examples are utilized to demonstrate the effectiveness of the developed controller design method.
Conservatism reduction for linear parameter‐varying control design facing inexact scheduling parameters illustrated on flight tests
Authors: Sato Masayuki , Peaucelle Dimitri
Published: July 2020

This article addresses the design problem of linear parameter‐varying (LPV) output feedback controllers that depend on inexact scheduling parameters for LPV systems. This problem has already been tackled and several methods have been proposed by overbounding the discrepancies between the actual scheduling parameters and the provided ones in the derivation of controller design condition. However, all methods in literature have conservatism in the overbounding, which is the main issue addressed in this article. We therefore propose a new overbounding for the discrepancies with the reverse use of Elimination lemma, which introduces no conservatism in theory. The new method is formulated in terms of bilinear matrix inequality, which is not tractable compared with linear matrix inequality, thus a practical design procedure composed of line search and iterative algorithm is shown. The effectiveness of our method is illustrated by an application to flight controller design for the lateral‐directional motions of a research airplane MuPAL‐α and the consequently conducted flight tests.
Geomorphological response to system‐scale river rehabilitation II: Main‐stem channel adjustments following reconnection of an ephemeral tributary
Authors: Marteau Baptiste , Gibbins Chris , Vericat Damià , Batalla Ramon J.
Published: July 2020

This paper describes changes in bed morpho‐dynamics and topography in the River Ehen, a regulated river in NW England (i.e., temperate climate) following a rehabilitation project that reconnected a formerly diverted headwater sub‐catchment back to its main‐stem. Sediment grain‐size distributions in the Ehen changed subtly and in rather complex ways following the reconnection. Changes were most evident in the riffle morphological unit, where gravel‐sized material accumulated in the first 2 years after the reconnection. All morphological units initially experienced an addition of fine sediment (size <8 mm) but by the end of the study the proportion of fine material in the bed matrix had returned to pre‐reconnection levels. Topographic changes were evident in some units, with net aggradation in the riffle and scour in the plane bed; there was no detectable change in the pool. Albeit limited, there was evidence of an increase in bed mobility, with field observations indicating that the new sediment is moving over the top of the largely static existing pavement, rather than interacting with it. Despite numerous uncertainties related mainly to the ephemeral nature of the tributary and, consequently, how much sediment it would deliver, evidence suggests that the main project objective is being met: there is a renewed supply of sediment now being delivered to the main‐stem Ehen at times and in quantities that are controlled by natural processes. Nevertheless, the river is still best considered to be in an adjustment phase, so assessment of its long term response to the reconnection requires continued monitoring.
Geomorphological response to system‐scale river rehabilitation I: Sediment supply from a reconnected tributary
Authors: Marteau Baptiste , Gibbins Chris , Vericat Damià , Batalla Ramon J.
Published: July 2020

This paper is the first of a pair that report the findings of a river rehabilitation project centred on the reconnection of a formerly diverted headwater tributary (Ben Gill) to its main‐stem river (the River Ehen). The present paper describes the geomorphic evolution of the tributary in the 2 years following its reconnection, with a particular focus on assessing the volumes of sediment now being supplied to the main‐stem Ehen. Structure‐from‐Motion photogrammetry was used to produce Digital Elevation Models (DEMs) of the newly connected tributary, with successive DEMs compared to assess topographic changes in the channel and quantify volumes of material exported. 3D errors in the DEMs were small relative to the scour and fill observed in the channel (error 0.016–0.056 m compared to up to 1.7 m vertical change between consecutive surveys). Erosion was the dominant process in the tributary channel, though this varied spatially and temporally. Over the 2‐year period, an estimated minimum of 384 m3 of coarse sediment was exported from Ben Gill and delivered to the confluence zone, where a new bar feature developed as a result. This estimate is twice as high as earlier ones. Analysis of the growth of this bar suggested that much of the material supplied by Ben Gill remains here temporarily, with onward conveyance constrained by the competence of the regulated main‐stem. The work shows that, thanks to the reconnection, this small (0.55 km2) ephemeral tributary (flowing for only around 20% of the time) has become a key source of sediment for the main‐stem Ehen. The second in the pair of papers focuses on the geomorphic responses of the main‐stem to this renewed supply of sediment.