bluuebunny/crossref_metadata_2025 huggingface dataset:
LncRNA GAS5 inhibits the proliferation and invasion of ovarian clear cell carcinoma via the miR‐31‐5p/ARID1A axis
Authors: Zhang Jian , Yang Zhong‐Mei , Huang Yu , Wang Ka‐Na , Xie Yao , Yang Nian
Published: August 2021

To investigate the role of the lncRNA growth arrest special 5 (GAS5) in ovarian clear cell carcinoma (OCCC), we measured the expression of GAS5 and miR‐31‐5p in OCCC tissue samples and OCCC cell lines using RT‐qPCR. MTT and colony formation assays were used to measure cell viability and colony formation ability. Cell invasion was determined by Transwell assays. The binding between GAS5 and miR‐31‐5p as well as miR‐31‐5p and ARID1A was determined by dual‐luciferase reporter assays. The ARID1A protein levels were detected using western blotting. Kaplan–Meier curves were used for the analysis of the 5‐year survival rate of patients with OCCC. GAS5 and ARID1A levels were significantly decreased, while miR‐31‐5p levels were strongly elevated in the OCCC tissues and cell lines. Patients with lower GAS5/ARID1A levels had shorter overall survival times. Overexpression of GAS5 or inhibition of miR‐31‐5p suppressed cell viability and invasion of OCCC cells and upregulated the protein levels of ARID1A. Moreover, overexpression of miR‐31‐5p reversed the effects of overexpression of GAS5. Cotransfection with pcDNA3.1‐GAS5 and miR‐31‐5p inhibitor led to the lowest cell viability and cell invasion rates. A dual‐luciferase reporter assay was performed to confirm the target relationship between GAS5 and miR‐31‐5p, as well as between miR‐31‐5p and ARID1A. LncRNA GAS5 inhibited cell viability and invasion of OCCC through activation of ARID1A by sponging miR‐31‐5p.
Prognostic Value of Tumor‐Infiltrating Lymphocytes in Sinonasal Mucosal Melanoma
Authors: Ledderose Stephan , Ledderose Carola , Penkava Josef , Ledderose Georg J.
Published: August 2021

Objectives/Hypothesis

Tumor‐infiltrating lymphocytes (TILs) predict better outcome in several types of cancers. However, the prognostic value of TILs in sinonasal mucosal melanoma (SNMM) is uncertain. Here, we investigated whether TILs can be used as a prognostic indicator for survival in SNMM.

Study Design

Retrospective cohort study.

Methods

Patient history and histologic specimens from 27 patients with primary SNMM were retrospectively analyzed. TIL grade was determined and associations between TILs and AJCC tumor stage, overall survival, and recurrence‐free survival were analyzed.

Results

Patients with TILs in the primary tumor classified as brisk or non‐brisk survived significantly longer than patients with SNMMs lacking lymphocyte infiltrates. Brisk TILs were associated with the lower T3 stage and increased recurrence‐free and 5‐year survival.

Conclusion

Our results indicate that TIL density is a strong prognostic factor for better survival in SNMM. Prospective studies with larger case numbers are warranted to determine whether TILs should be included in future AJCC staging guidelines.

Level of Evidence

3 Laryngoscope, 132:1334–1339, 2022
A soil sampling design for arable land quality observation by using SPCOSA–CLHS hybrid approach
Authors: Wan Changjun , Kuzyakov Yakov , Cheng Changxiu , Ye Sijing , Gao Bingbo , Gao Peichao , Ren Shuyi , Yun Wanqi
Published: August 2021

Arable land quality has been evaluated through weighted average of indicators related to soil properties and tillage technics to present the most basic function of cropland: food production potential. A hybrid sampling method spatial coverage sampling and random sampling–conditioned Latin hypercube sampling (SPCOSA–CLHS) was designed for arable land quality observation network in this paper. The SPCOSA–CLHS integrates the uniform spatial partitioning results generated by the spatial coverage sampling and random sampling (SPCOSA) into the conditioned Latin hypercube sampling (CLHS) method along with other arable land quality indicators such as field slope, soil bulk density, organic matter content, thickness of plough layer and irrigation. Then, SPCOSA, CLHS, SPCOSA–CLHS, CLHS with x and y coordinates as covariates (XY‐CLHS), random sampling method (RSM) were compared using the example of Heilongjiang Province. The sample population covers 12,147,008 grid cells and 17 arable land quality indicators. Five parameters: information entropy, Kullback–Leibler divergence, similarity distance, expression ability to local spatial heterogeneity of arable land quality and distribution homogeneity of sampling results were used to compare the applicability of these methods for overall arable land quality. The SPCOSA–CLHS can better trade off sampling result's representative ability to the population and spatial heterogeneity of arable land quality, as well as its samples have advantages of spatially uniform distribution. When the sample size is between 5000 and 20,000, all methods show good applicability. When the sample size is below 5000, however, the differences among these methods become significant. SPCOSA and random sampling method offset most dramatically. Based on this detailed comparison of the five sampling strategy approaches, we strongly recommend to use SPCOSA–CLHS to design arable land quality observation.
Utilizing side streams of pulse protein processing: A review
Authors: Ratnayake Wajira S. , Naguleswaran Sabaratnam
Published: August 2021

Plant‐based protein ingredients are gaining popularity among consumers for various reasons such as the increasing demand for high‐protein diets, sustainability of the sources, and negative perceptions associated with animal proteins. Main source for plant proteins is pulses such as peas and beans. Pulse seeds contain up to 25% (w/w) protein, whereas nonprotein components are present in much higher proportions. Starch, fiber, and soluble material are generated as side streams of pulse protein manufacturing processes. These side streams, unless properly utilized, create both economic and environmental challenges. Therefore, the utilization of process side streams is of paramount importance for the overall sustainability of the plant protein manufacturing processes. This review summarizes the key research advances and potential opportunities in valorization of side streams from pulse protein manufacturing processes.
Physical Origin of Distinct Mechanical Properties of Polymer Tethered Graphene Nanosheets Reinforced Polymer Nanocomposites Revealed by Nonequilibrium Molecular Dynamics Simulations
Authors: Zhang Xu , Chen Jialiang , Liu Tianxi
Published: August 2021

A non‐equilibrium deformation simulation based on standard molecular dynamics is employed to reveal the physical origin of distinct mechanical properties of polymer nanocomposites (PNCs) reinforced by polymer tethered graphene nanosheets (P/G‐T). The effect of tethered polymer length (L) and interaction strength on the mechanical properties, including tensile stress, modulus, and yield strength, are examined. The simulation results show that the P/G‐T systems exhibit improved mechanical properties as L and interaction strength increases. The strengthening in attractive interaction between matrix polymer and tethered polymer has a better effect on mechanical properties than that between P and graphene nanosheets. It is found that the bond orientation and nonbonding potential is of crucial importance in determining the mechanical properties of the P/G‐T nanocomposite systems. The calculations of radial distribution functions and mean‐squared displacement are further performed to reveal the physical origin of enhanced mechanical properties, suggesting that the stronger interfacial interactions will induce the closer packing distance with smaller free volume, higher polymer chain entanglement, and higher restriction of polymer chain movement, which synergistically contribute to the improvement in the mechanical properties. The results may provide useful guidance for promoting the development and practical application of the advanced PNCs with excellent performance.
Neuropathological Findings in a Case of Parkinsonism and Developmental Delay Associated with a Monoallelic Variant in PLXNA1
Authors: O'Shea Sarah A. , Hickman Richard A. , Cortes Etty , Vonsattel Jean Paul , Fahn Stanley , Okur Volkan , Alcalay Roy N. , Chung Wendy K.
Published: August 2021

Background

PLXNA1 encodes for Plexin‐A, a transmembrane protein expressed in the developing nervous system. Mutations in this gene have been associated with developmental delay but have not been previously associated with the development of parkinsonism.

Objectives

To describe the case of a 38‐year‐old patient with developmental delay who developed parkinsonism later in life.

Methods

Post‐mortem exome sequencing was performed with confirmation by Sanger sequencing. Brain autopsy was also performed.

Results

Post‐mortem exome sequencing on the proband identified a heterozygous predicted nonsense PLXNA1 variant (c.G3361T:p.Glu1121Ter). Pathology demonstrated arhinencephaly with brainstem heterotopia, diffuse Lewy body disease, and frontotemporal lobar dementia‐tau.

Conclusions

This case of a patient with developmental delay and parkinsonism with PLXNA1 mutation highlights a need for assessing long‐term outcomes of individuals with neurodevelopmental disorders, as well as the need for genetic testing in adults. It also suggests that the link between PLXNA1 and α‐synuclein should be explored in the future. © 2021 International Parkinson and Movement Disorder Society
Applicable and cost‐efficient microplastic analysis by quantitative 1H‐NMR spectroscopy using benchtop NMR and NoD methods
Authors: Peez Nadine , Rinesch Torsten , Kolz Jürgen , Imhof Wolfgang
Published: August 2021

In continuation of our work on the proof‐of‐concept that quantitative NMR spectroscopy may be a valuable tool in microplastic (MP) analysis and quantification, we present here investigations using low‐field NMR spectrometers and nondeuterated solvents for the analysis of solutions of MP particles in suitable solvents. The use of low‐field NMR spectrometers (benchtop NMR) that are considerably more cost‐effective in terms of purchase and operating costs compared with high‐field NMR spectrometers and the use of nondeuterated solvents (NoD method) leads to an applicable and cost‐efficient method for mass‐based MP analysis. For benchtop 80‐MHz NMR, limits of detection for polyvinylchloride (PVC), polyethylene terephthalate (PET), and polystyrene (PS) are in the same range as if a high‐field 500‐MHz NMR spectrometer was used for quantification (500 MHz: PET 1 μg/ml, PVC 42 μg/ml, and PS 9 μg/ml; 80 MHz: PET 4 μg/ml, PVC 19 μg/ml, and PS 21 μg/ml) for polymers being dissolved in deuterated solvents. The same is true for the corresponding limits of quantification. Moreover, it is shown for the first time that quantitative determination of the mass concentration of PET, PVC, and PS is also possible using NoD methods by evaluating the integrals of polymer‐specific signals relative to an internal or external standard. Detection limits for NoD methods are in a similar range as if deuterated solvents were used (PET 2 μg/ml, PVC 39 μg/ml, and PS 8 μg/ml) using a high‐field 500‐MHz spectrometer or the 80‐MHz spectrometer (PET 5 μg/ml).
Healthcare professionals’ sense of coherence of parental involvement in neonatal intensive care units: A framework synthesis
Authors: Chan Shu Hui , Shorey Shefaly
Published: August 2021

Family‐centered care is recognized as the gold standard in pediatric healthcare practice. However, despite the acknowledgment of its benefits and importance, inconsistent and questionable implementation persists in neonatal intensive care units (NICUs) without a consolidated understanding of healthcare professionals’ experiences. Therefore, this review aims to explore and consolidate healthcare professionals’ perspectives on parental participation in the NICU. A systematic review of qualitative studies was conducted following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Seven electronic databases were searched from their respective dates of inception until December 30, 2020. Twenty‐eight studies were included in this review. The analysis was conducted via a framework synthesis approach using Antonovsky's Sense of Coherence theory. Three over‐arching themes, guided by Antonovsky's Sense of Coherence theory emerged: (1) “Comprehensibility of parental involvement in family‐centered care,” (2) “Manageability of parental involvement in care and decision‐making,” and (3) “Meaningfulness of parental involvement in shared decision‐making in neonatal care,” with nine corresponding subthemes. Healthcare professionals had mixed views of parental involvement, recognizing the benefits attributed to infants and parents, but were greatly hindered by organizational, environmental, and personal obstacles that weakened their sense of coherence in coping with the situation, making them feel unconfident and unprepared to involve parents in care. To cope, more integrated and formalized support was required. Organizational, environmental, and policy changes, as well as psychological support, were strategies identified to enhance healthcare professionals’ sense of coherence, and consequently, their ability to cope.
An exploratory first‐in‐man study to investigate the pharmacokinetics and safety of liposomal dexamethasone at a 2‐ and 1‐week interval in patients with metastatic castration resistant prostate cancer
Authors: Vrouwe Josephina P. M. , Kamerling Ingrid M. C. , van Esdonk Michiel J. , Metselaar Josbert M. , Stuurman Frederik E. , van der Pluijm Gabri , Burggraaf Jacobus , Osanto Susanne
Published: August 2021

Dexamethasone has antitumor activity in metastatic castration resistant prostate cancer (mCRPC). We aimed to investigate intravenous liposome‐encapsulated dexamethasone disodium phosphate (liposomal dexamethasone) administration in mCRPC patients.

In this exploratory first‐in‐man study, patients in part A received a starting dose of 10 mg followed by five doses of 20 mg liposomal dexamethasone at 2‐week intervals. Upon review of part A safety, patients in part B received 10 weekly doses of 18.5 mg. Primary outcomes were safety and pharmacokinetic profile, secondary outcome was antitumor efficacy.

Nine mCRPC patients (5 part A, 4 part B) were enrolled. All patients experienced grade 1–2 toxicity, one (part B) patient experienced grade 3 toxicity (permanent bladder catheter‐related urosepsis). No infusion‐related adverse events occurred. One patient had upsloping glucose levels ≤9.1 mmol/L. Trough plasma concentrations of liposomal‐ and free dexamethasone were below the lower limit of quantification (LLOQ) in part A, and above LLOQ in three patients in part B (t1/2 ~50 h for liposomal dexamethasone), trough concentrations of liposomal‐ and free dexamethasone increased toward the end of the study. In seven of nine patients (78%) patients, stable disease was observed in bone and/or CT scans at follow‐up, and in one (part B) of these seven patients a >50% PSA biochemical response was observed.

Bi‐ and once weekly administrations of IV liposomal dexamethasone were well‐tolerated. Weekly dosing enabled trough concentrations of liposomal‐ and free dexamethasone >LLOQ. The data presented support further clinical investigation in well‐powered studies.

Clinical trial registration: ISRCTN 10011715.
Lumbriculus variegatus: A novel organism for in vivo pharmacology education
Authors: Seeley Aidan , Bellamy Caitlin , Davies Nia A. , Wallace Melisa J.
Published: August 2021

Pharmacology graduates require an understanding of both in vitro and in vivo drug responses but there has been a decline in animal use in pharmacology education over the last 30 years. To address this, we present the novel invertebrate model, Lumbriculus variegatus, for in vivo testing of drugs in a teaching environment. We have developed two novel behavioral assays: the stereotypical movement assay, which measures the effect of drugs on the ability of L. variegatus to perform stereotypical movements following tactile stimulation, and the free locomotion assay, which measures drug effects on unstimulated movement. We report the effects of compounds with diverse pharmacodynamic properties on L. variegatus using these assays. The ryanodine receptor antagonist, dantrolene, altered the unstimulated movement of L. variegatus at 5 μM, whereas stimulated movement was inhibited at ≥25 μM. Lidocaine, a voltage‐gated sodium channel blocker, and quinine, a nonselective sodium and potassium channel blocker, reduced both stimulated and unstimulated L. variegatus movement at ≥0.5 mM. Inhibitory effects of quinine persisted for up to 24 h after drug removal, whereas lidocaine effects were reduced 10 min after drug removal. Herein, we provide proof‐of‐concept utilization of L. variegatus as an organism for use in in vivo pharmacology education but without regulatory constraints or the need for specialized equipment and training.
Ultrahigh Photoresponsive Photodetector Based on Graphene/SnS2 van der Waals Heterostructure
Authors: Cui Boyao , Han Jun , Xing Yanhui , Lv Weiming , Lei Ting , Ma Haixin , Zeng Zhongming , Zhang Baoshun
Published: August 2021

SnS2 exhibits a high absorbance coefficient and strong photoconductive properties in ultraviolet–visible regions, making it a promising photodetector with excellent photoelectric performance. The characteristic of a large yield of photocarriers in SnS2 with the high mobility of graphene is combined and a vertical graphene/SnS2 van der Waals heterostructure photodetector is fabricated, which can obtain effective electron–hole pairs separation under the built‐in electric field, thus having a high photoresponse. It has the characteristics of ultrahigh responsivity (6.35 × 105 A W−1) and high external quantum efficiency (2.15 × 108%) under 365 nm light. Such high‐performance graphene/SnS2 heterostructures may find promising applications in future optoelectronic devices.
Positive Temperature Coefficient and Electrical Conductivity Investigation of Hybrid Nanocomposites Based on High‐Density Polyethylene/Graphene Nanoplatelets/Carbon Black
Authors: Shafiei Mohammad , Ghasemi Ismaeil , Gomari Sepideh , Abedini Ali , Jamjah Roghayeh
Published: August 2021

Hybrid nanocomposites of high‐density polyethylene have been prepared via the melt‐mixing method in the presence of different amounts of graphene nanoplatelets (GNPs) and conductive carbon black (CB). The electrical conductivity, positive temperature coefficient (PTC), and the correlation between crystallinity and electrical conductivity of hybrid nanocomposites are investigated to study the effect of crystallinity on electrical conductivity. The samples are characterized using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X‐ray diffraction (XRD), and electrical resistivity. SEM micrographs reveal good distribution of CB and GNPs in nanocomposites. According to DSC and XRD results, the crystallinity of samples decreases by the addition of CB and GNP. The electrical conductivity of all the samples increases, whereas in the sample 16% of CB and 1% of GNP electrical conductivity decrease due to GNP acting as a heterogeneous nucleating agent and the numerous incomplete and small crystals formation. The highest electrical conductivity (1.46×10−4 S cm−1) is obtained in the sample high‐density polyethylene (HDPE)/CB18/GNP1, which shows high increment in the PTC curve in the range of 105−120 °C. Also, repeatability and reversibility of PTC in this sample show good potential for use in different applications such as thermistors, temperature sensors, and self‐regulating heaters.
Parallel coordinate order forhigh‐dimensionaldata
Authors: Tilouche Shaima , Partovi Nia Vahid , Bassetto Samuel
Published: August 2021

Visualization of high‐dimensional data is counter‐intuitive using conventional graphs. Parallel coordinates are proposed as an alternative to explore multivariate data more effectively. However, it is difficult to extract relevant information through the parallel coordinates when the data are high‐dimensional with thousands of overlapping lines. The order of the axes determines the perception of information on parallel coordinates. Thus, the information between attributes remains hidden if coordinates are improperly ordered. Here we propose a general framework to reorder the coordinates. This framework is general enough to cover a wide range of data visualization objectives. It is also flexible enough to contain many conventional ordering measures. Consequently, we present the coordinate ordering binary optimization problem and enhance it to achieve a computationally efficient greedy approach that suits high‐dimensional data. Our approach is applied to wine data and genetic data. The purpose of dimension reordering of wine data is to highlight attributes' dependence. Genetic data are reordered to enhance cluster detection. The proposed framework shows that it is able to adapt the criteria for the visualization objective.
COVID‐19's ambiguous parcel: Agency, dignity, and claims to a rightful share during food parcel distribution in lockdown South Africa
Authors: Ekeland Magnus Godvik
Published: August 2021

During the South African lockdown, food relief was largely delivered by civil society, after the government failed to honor its pledge to provide for the population. By taking a local food parcel initiative in a small rural township as an ethnographic case study, this article examines why the attempt to mimic government food distribution generated dissatisfaction and tension in the targeted community. At the heart of this argument is the way the local parcel project created ambiguous anticipation regarding the consequences for residents' experience of dignity, as it undermined an established binary understanding of economic dependency. This understanding clearly distinguishes between relationships within the community and those with the government. Proximity and intimacy increased the risk of public humiliation arising from indebtedness, while dependence on the government did not inevitably generate the same anxiety. Agency is identified as a key signifier to understand strategies for upholding dignity in the different relationships. This article examines different stakeholders' spontaneous and creative attempts to control the relational outcome of the distribution. It discusses how narratives about the distribution as a rightful share to the community's wealth emerged among potential recipients in an attempt to negate any notion of personalized reciprocity following the distribution.
Understanding the Impedance Response of Lithium Polysulfide Symmetric Cells
Authors: Song Yun-Wei , Peng Yan-Qi , Zhao Meng , Lu Yang , Liu Jia-Ning , Li Bo-Quan , Zhang Qiang
Published: August 2021

Lithium–sulfur (Li–S) batteries are highly considered for next‐generation energy storage due to their ultrahigh theoretical energy density of 2600 Wh kg−1. The conversion reactions between lithium polysulfides (LiPSs) constitute the core process in working Li–S batteries. Electrochemical impedance spectroscopy (EIS) analysis of LiPS symmetric cells is an effective tool to provide detailed information on the LiPS conversion reactions and direct further kinetic promotion. However, reasonable interpretation of the EIS responses is so far insufficiently addressed without a well‐defined equivalent circuit. Herein, a systematic analysis on the EIS responses of LiPS symmetric cells is conducted to provide a comprehensible equivalent circuit. Interfacial contact, surface reaction, and diffusion are decoupled according to their respective characteristic frequency using the distribution of relaxation time analysis method. A well‐defined equivalent circuit is proposed to accurately fit the experimental EIS responses, unambiguously interpret key parameters, and be feasible with a wide range of experimental conditions. This work presents the methodology of understanding the EIS responses of LiPS symmetric cells and inspires analogous analysis on vital electrochemical processes.
Turning the Page: Advancing Detection Platforms for Sulfate Reducing Bacteria and their Perks
Authors: Asif Muhammad , Aziz Ayesha , Ashraf Ghazala , Iftikhar Tayyaba , Sun Yimin , Liu Hongfang
Published: August 2021

Sulfate reducing bacteria (SRB) are blamed as main culprits in triggering huge corrosion damages by microbiologically influenced corrosion. They obtained their energy through enzymatic conversion of sulfates to sulfides which are highly corrosive. However, conventional SRB detection methods are complex, time‐consuming and are not enough sensitive for reliable detection. The advanced biosensing technologies capable of overcoming the aforementioned drawbacks are in demand. So, nanomaterials being economical, environmental friendly and showing good electrocatalytic properties are promising candidates for electrochemical detection of SRB as compared with antibody based assays. Here, we summarize the recent advances in the detection of SRB using different techniques such as PCR, UV visible method, fluorometric method, immunosensors, electrochemical sensors and photoelectrochemical sensors. We also discuss the SRB detection based on determination of sulfide, typical metabolic product of SRB.
Identifying relevant outcomes in the progression of Alzheimer's disease; what do patients and care partners want to know about prognosis?
Authors: Mank Arenda , van Maurik Ingrid S. , Bakker Els D. , van de Glind Esther M. M. , Jönsson Linus , Kramberger Milica G. , Novak Petr , Diaz Ana , Gove Dianne , Scheltens Philip , van der Flier Wiesje M. , Visser Leonie N. C.
Published: August 2021

Background

Prognostic studies in the context of Alzheimer's disease (AD) mainly predicted time to dementia. However, it is questionable whether onset of dementia is the most relevant outcome along the AD disease trajectory from the perspective of patients and their care partners. Therefore, we aimed to identify the most relevant outcomes from the viewpoint of patients and care partners.

Methods

We used a two‐step, mixed‐methods approach. As a first step we conducted four focus groups in the Netherlands to elicit a comprehensive list of outcomes considered important by patients (n = 12) and care partners (n = 14) in the prognosis of AD. The focus groups resulted in a list of 59 items, divided into five categories. Next, in an online European survey, we asked participants (n = 232; 99 patients, 133 care partners) to rate the importance of all 59 items (5‐point Likert scale). As participants were likely to rate a large number of outcomes as “important” (4) or “very important” (5), we subsequently asked them to select the three items they considered most important.

Results

The top‐10 lists of items most frequently mentioned as “most important” by patients and care partners were merged into one core outcome list, comprising 13 items. Both patients and care partners selected outcomes from the category “cognition” most often, followed by items in the categories “functioning and dependency” and “physical health.” No items from the category “behavior and neuropsychiatry” and “social environment” ended up in our core list of relevant outcomes.

Conclusion

We identified a core list of outcomes relevant to patients and care partner, and found that prognostic information related to cognitive decline, dependency, and physical health are considered most relevant by both patients and their care partners.
Budesonide as induction therapy for incomplete microscopic colitis: A randomised, placebo‐controlled multicentre trial
Authors: Münch Andreas , Mihaly Emese , Nagy Ferenc , Madisch Ahmed , Kupčinskas Juozas , Miehlke Stephan , Bohr Johan , Bouma Gerd , Guardiola Jordi , Belloc Blanca , Shi Chunliang , Aust Daniela , Mohrbacher Ralf , Greinwald Roland , Munck Lars Kristian
Published: August 2021

Background and aims

Incomplete microscopic colitis (MCi) is a subtype of microscopic colitis (MC). Budesonide is recommended as a first‐line treatment for MC. However, randomised trials on efficacy of treatment in MCi are missing. We therefore performed a randomised, placebo‐controlled trial to evaluate budesonide as induction therapy for MCi.

Methods

Patients with active MCi were randomly assigned to either budesonide 9 mg once daily or placebo for 8 weeks in a double‐blind, double‐dummy design. The primary endpoint was clinical remission, defined as a mean of <3 stools/day and a mean of <1 watery stool/day in the 7 days before week 8.

Results

Due to insufficient patient recruitment, the trial was discontinued prematurely. The intention‐to‐treat analysis included 44 patients (21 budesonide and 23 placebo). The primary endpoint of clinical remission at week 8 was obtained by 71.4% on budesonide and 43.5% on placebo (p = 0.0582). All clinical secondary endpoints were in favour of budesonide. Budesonide decreased the number of soft or watery stools (16.3 vs. 7.7, p = 0.0186) and improved health‐related quality of life for all four dimensions of the short health scale. Adverse events with a suspected relation to study drug were reported in one patient in the budesonide group and two patients in the placebo group. Neither serious nor severe adverse events occurred during the double‐blind phase.

Conclusions

Budesonide decreased the frequency of soft or watery stools and improved the patients' quality of life significantly in MCi, but the primary endpoint was not met due to the low sample size (type 2 error). Budesonide was safe and well tolerated during the 8‐weeks treatment course.
Emerging two‐dimensional monoelemental materials (Xenes): Fabrication, modification, and applications thereof in the field of bioimaging as nanocarriers
Authors: Chen Weijian , Pan Wanwan , Wang Jingwen , Cheng Liang , Wang Jing , Song Lei , Hu Yuan , Ma Xiaopeng
Published: August 2021

In recent years, more and more research enthusiasm has been devoted to the development of emerging two‐dimensional (2D) monoelement materials (Xenes) and explored potential applications in various fields, especially biomedicine and bioimaging. The inspiring results attribute to their excellent physicochemical properties, including adjustable band gap, surface electronic layout characteristics, and so on, making it easier for surface modification in order to meet designated needs. As a popular interdisciplinary research frontier, a variety of methods for fabricating 2D Xenes have recently been adopted for pre‐preparing future practical bioimaging applications, which implies that these materials will have broad clinical application prospects in the future. In this review, we will concentrate on the family of 2D Xenes and summarize their fabrication and modification methods firstly. Then, their applications in bioimaging as nanocarriers will be described according to the Periodic Table of Elements. In addition, current challenges and prospects for further clinical applications will be under discussion and use black phosphorus as a typical example. At last, general conclusion will be made that it is worth expecting that 2D Xenes will play a key role in the next generation of oncologic bioimaging in the future.

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials

Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine
Two fluorescent copper phosphonate complexes for sensing antibiotics, ketones and Fe3+ in water
Authors: Zhang Yu‐Tong , Ruan Jia‐Xin , Ma Dong‐Sheng , Gao Jin‐Sheng , Wu Guang , Liu Yi‐Fu , Yu Ying‐Hui
Published: August 2021

As the most attractive and fastest growing fluorescent sensing materials, metal‐organic compounds have demonstrated great potential for the detection of various types of chemicals. Two fluorescent phosphonate complexes [Cu3O2(HL)2 ⋅ 2H2O] (1) and [Cu(H2L)2 ⋅ 3H2O] (2) with diverse structures were designed and synthesized for this purpose from ((2’‐cyano‐[1,1’‐biphenyl]‐4‐yl)methyl)phosphonic acid (H2L) and copper ions with various valence state under solvothermal conditions. The structures of 1 and 2 are determined by single X‐ray crystal diffraction, and further characterized by elemental analysis, IR, TGA and PXRD. The two complexes demonstrate diverse properties on sensing Fe3+ ions, ketone and some antibiotics, and the according detection limits are obtained, indicating which could be applied as a fast, recyclable, and multi‐responsive fluorescence sensor. The sensing activity diversity between 1 and 2 toward different analytes was also discussed based on the possible sensing mechanisms to further explore the possible factors affecting the sensibility of the materials.
Synthesis of Directed, Tridentate Lewis Acids Based on a Trisilacyclohexane‐Backbone via Hydrosilylation
Authors: Rudlof Jens , Neumann Beate , Stammler Hans‐Georg , Mitzel Norbert W.
Published: August 2021

Based on a semiflexible trisilacyclohexane framework a series of directed, tridentate Lewis acids were synthesized by hydrosilylation using various (chloro)methylsilanes. The axial alignment of the three electron deficient functions in one spatial direction allows creating poly‐Lewis acids with chalice‐like cavities. The directed, tridentate poly‐Lewis acids were obtained in quantitative yields and characterized by multinuclear NMR spectroscopy, CHN analysis and X‐ray diffraction experiments. The Lewis acidity of the introduced silicon functions was quantified and classified using the Gutmann‐Beckett method.
The Role of Public Policies in Enhancing Cultural and Creative Industries: An Analysis of Public Policies Related to Music in Colombia
Authors: Gómez-Reyes Flor Marleny , Catalá-Pérez Daniel , de-Miguel-Molina María
Published: August 2021

This chapter aims to analyse how public policies can influence the development of clusters around the cultural and creative industries (CCIs), more specifically the music sector in the case of Bogota, the capital of Colombia. Since the 1990s, the cultural and creative industry has attracted academia and governments across the world to create clusters and economic development, mainly in developing countries such as Colombia. Yet to ensure music industry success, public policies that improve CCIs’ resources and capacities need to be provided. This paper focuses on the impact of public policies on CCIs in Bogota and how different clusters have been created, especially related to music. Moreover, we examine how national strategy has had a positive influence on local strategy with clusters being boosted in devalued areas of the city, bringing improvements in their economic development.
A gravitino distance conjecture
Authors: Castellano Alberto , Font Anamaría , Herráez Alvaro , Ibáñez Luis E.
Published: August 2021

Abstract

We conjecture that in a consistent supergravity theory with non-vanishing gravitino mass, the limit m3/2 → 0 is at infinite distance. In particular one can write Mtower ~ $$ {m}_{3/2}^{\delta } $$

m

3
/
2

δ

so that as the gravitino mass goes to zero, a tower of KK states as well as emergent strings becomes tensionless. This conjecture may be motivated from the Weak Gravity Conjecture as applied to strings and membranes and implies in turn the AdS Distance Conjecture. We test this proposal in classical 4d type IIA orientifold vacua in which one obtains a range of values $$ \frac{1}{3} $$

1
3

≤ δ ≤ 1. The parameter δ is related to the scale decoupling exponent in AdS vacua and to the α exponent in the Swampland Distance Conjecture for the type IIA complex structure. We present a general analysis of the gravitino mass in the limits of moduli space in terms of limiting Mixed Hodge Structures and study in some detail the case of two-moduli F-theory settings. Moreover, we obtain general lower bounds δ ≥$$ \frac{1}{3},\frac{1}{4} $$

1
3

,

1
4

for Calabi-Yau threefolds and fourfolds, respectively. The conjecture has important phenomenological implications. In particular we argue that low-energy supersymmetry of order 1 TeV is only obtained if there is a tower of KK states at an intermediate scale, of order 108 GeV. One also has an upper bound for the Hubble constant upon inflation H ≲ $$ {m}_{3/2}^{\delta }{M}_{\mathrm{P}}^{\left(1-\delta \right)} $$

m

3
/
2

δ

M
P

1
−
δ

.
Resolving spacetime singularities in flux compactifications & KKLT
Authors: Carta Federico , Moritz Jakob
Published: August 2021

Abstract

In flux compactifications of type IIB string theory with D3 and seven-branes, the negative induced D3 charge localized on seven-branes leads to an apparently pathological profile of the metric sufficiently close to the source. With the volume modulus stabilized in a KKLT de Sitter vacuum this pathological region takes over a significant part of the entire compactification, threatening to spoil the KKLT effective field theory. In this paper we employ the Seiberg-Witten solution of pure SU(N) super Yang-Mills theory to argue that wrapped seven-branes can be thought of as bound states of more microscopic exotic branes. We argue that the low-energy worldvolume dynamics of a stack of n such exotic branes is given by the (A1, An−1) Argyres-Douglas theory. Moreover, the splitting of the perturbative (in α′) seven-brane into its constituent branes at the non-perturbative level resolves the apparently pathological region close to the seven-brane and replaces it with a region of $$ \mathcal{O} $$
O
(1) Einstein frame volume. While this region generically takes up an $$ \mathcal{O} $$
O
(1) fraction of the compactification in a KKLT de Sitter vacuum we argue that a small flux superpotential dynamically ensures that the 4d effective field theory of KKLT remains valid nevertheless.
Exploring the landscape for soft theorems of nonlinear sigma models
Authors: Rodina Laurentiu , Yin Zhewei
Published: August 2021

Abstract

We generalize soft theorems of the nonlinear sigma model beyond the$$ \mathcal{O} $$O(p2) amplitudes and the coset of SU(N) × SU(N)/SU(N). We first discuss the universal flavor ordering of the amplitudes for the Nambu-Goldstone bosons, so that we can reinterpret the known$$ \mathcal{O} $$O(p2) single soft theorem for SU(N) × SU(N)/SU(N) in the context of a general symmetry group representation. We then investigate the special case of the fundamental representation of SO(N), where a special flavor ordering of the “pair basis” is available. We provide novel amplitude relations and a Cachazo-He-Yuan formula for such a basis, and derive the corresponding single soft theorem. Next, we extend the single soft theorem for a general group representation to$$ \mathcal{O} $$O(p4), where for at least two specific choices of the$$ \mathcal{O} $$O(p4) operators, the leading non-vanishing pieces can be interpreted as new extended theory amplitudes involving bi-adjoint scalars, and the corresponding soft factors are the same as at$$ \mathcal{O} $$O(p2). Finally, we compute the general formula for the double soft theorem, valid to all derivative orders, where the leading part in the soft momenta is fixed by the$$ \mathcal{O} $$O(p2) Lagrangian, while any possible corrections to the subleading part are determined by the$$ \mathcal{O} $$O(p4) Lagrangian alone. Higher order terms in the derivative expansion do not contribute any new corrections to the double soft theorem.
Systematics of the α′ expansion in F-theory
Authors: Cicoli M. , Quevedo F. , Savelli R. , Schachner A. , Valandro R.
Published: August 2021

Abstract

Extracting reliable low-energy information from string compactifications notoriously requires a detailed understanding of the UV sensitivity of the corresponding effective field theories. Despite past efforts in computing perturbative string corrections to the tree-level action, neither a systematic approach nor a unified framework has emerged yet. We make progress in this direction, focusing on the moduli dependence of perturbative corrections to the 4D scalar potential of type IIB Calabi-Yau orientifold compactifications. We proceed by employing two strategies. First, we use two rescaling symmetries of type IIB string theory to infer the dependence of any perturbative correction on both the dilaton and the Calabi-Yau volume. Second, we use F/M-theory duality to conclude that KK reductions on elliptically-fibred Calabi-Yau fourfolds of the M-theory action at any order in the derivative expansion can only generate (α′)even corrections to the 4D scalar potential, which, moreover, all vanish for trivial fibrations. We finally give evidence that (α′)odd effects arise from integrating out KK and winding modes on the elliptic fibration and argue that the leading no-scale breaking effects at string tree-level arise from (α′)3 effects, modulo potential logarithmic corrections.
The compartmental approach to revision of partial knee arthroplasty results in nearer-normal gait and improved patient reported outcomes compared to total knee arthroplasty
Authors: Garner Amy J. , Dandridge Oliver W. , van Arkel Richard J. , Cobb Justin P.
Published: August 2021

Purpose

This study investigated the gait and patient reported outcome measures of subjects converted from a partial knee arthroplasty to combined partial knee arthroplasty, using a compartmental approach. Healthy subjects and primary total knee arthroplasty patients were used as control groups.

Methods

Twenty-three patients converted from partial to combined partial knee arthroplasty were measured on the instrumented treadmill at top walking speeds, using standard gait metrics. Data were compared to healthy controls (n = 22) and primary posterior cruciate-retaining total knee arthroplasty subjects (n = 23) where surgery were performed for one or two-compartment osteoarthritis. Groups were matched for age, sex and body mass index. At the time of gait analysis, combined partial knee arthroplasty subjects were median 17 months post-revision surgery (range 4–81 months) while the total knee arthroplasty group was median 16 months post-surgery (range 6–150 months). Oxford Knee Scores and EuroQol-5D 5L scores were recorded at the time of treadmill assessment, and results analysed by question and domain.

Results

Subjects revised from partial to combined partial knee arthroplasty walked 16% faster than total knee arthroplasty (mean top walking speed 6.4 ± 0.8 km/h, vs. 5.5 ± 0.7 km/h p = 0.003), demonstrating nearer-normal weight-acceptance rate (p < 0.001), maximum weight-acceptance force (p < 0.006), mid-stance force (p < 0.03), contact time (p < 0.02), double support time (p < 0.009), step length (p = 0.003) and stride length (p = 0.051) compared to primary total knee arthroplasty. Combined partial knee arthroplasty subjects had a median Oxford Knee Score of 43 (interquartile range 39–47) vs. 38 (interquartile range 32–41, p < 0.02) and reported a median EQ-5D 0.94 (interquartile range 0.87–1.0) vs. 0.84 (interquartile range 0.80–0.89, p = 0.006).

Conclusion

This study finds that a compartmental approach to native compartment degeneration following partial knee arthroplasty results in nearer-normal gait and improved patient satisfaction compared to total knee arthroplasty.

Level of evidence

III.
A numerical investigation of Brockett’s ensemble optimal control problems
Authors: Bartsch Jan , Borzì Alfio , Fanelli Francesco , Roy Souvik
Published: August 2021

This paper is devoted to the numerical analysis of non-smooth ensemble optimal control problems governed by the Liouville (continuity) equation that have been originally proposed by R.W. Brockett with the purpose of determining an efficient and robust control strategy for dynamical systems. A numerical methodology for solving these problems is presented that is based on a non-smooth Lagrange optimization framework where the optimal controls are characterized as solutions to the related optimality systems. For this purpose, approximation and solution schemes are developed and analysed. Specifically, for the approximation of the Liouville model and its optimization adjoint, a combination of a Kurganov–Tadmor method, a Runge–Kutta scheme, and a Strang splitting method are discussed. The resulting optimality system is solved by a projected semi-smooth Krylov–Newton method. Results of numerical experiments are presented that successfully validate the proposed framework.
The Effect of Teriparatide Treatment on the Risk of Fragility Fractures in Postmenopausal Women with Osteoporosis: Results from the Asian and Latin America Fracture Observational Study (ALAFOS)
Authors: Chen Chung-Hwan , Elsalmawy Abdulaziz H. , Ish-Shalom Sophia , Lim Seung-Jae , AlAli Nadia S. , Cunha-Borges Joao L. , Yang Huilin , Casas Noemi , Altan Lale , Belaya Zhanna , Marin Fernando , Moll Thomas , Gurbuz Sirel , Brnabic Alan , Pavo Imre , Florez Sandra
Published: August 2021

The Asian and Latin America Fracture Observational Study (ALAFOS) is a prospective, observational, single-arm study conducted in 20 countries across Asia, Latin America and the Middle East. ALAFOS evaluated new clinical vertebral and non-vertebral fragility fractures in relation to time on teriparatide, in postmenopausal women with osteoporosis in real-life clinical practice. Clinical fragility fractures, back pain, and health-related quality of life (HRQoL) were recorded in 6-month intervals for ≤ 24 months during teriparatide treatment and up to 12-months post-treatment. Data were analysed with piecewise exponential regression with inverse probability weighting for time to event outcomes and mixed-model repeated measures for back pain and HRQoL. 3054 postmenopausal women started teriparatide and attended ≥ one follow-up visit (mean [SD] age 72.5 [10.4] years). The median (95% CI) time to treatment discontinuation was 22.0 months (21.2, 22.8). During the treatment period, 111 patients (3.6%) sustained 126 clinical fractures (2.98 fractures/100 patient-years). Rates of new clinical fragility fractures were significantly decreased during the > 6–12, > 12–18, and > 18–24-month periods, as compared with the first 6 months of treatment (hazard ratio [HR] 0.57; 95% CI 0.37, 0.88; p = 0.012; HR 0.35; 95% CI 0.19, 0.62; p < 0.001; HR 0.43; 95% CI 0.23, 0.83; p = 0.011; respectively). Patients also reported an improvement in back pain and HRQoL (p < 0.001). These results provide data on the real-world effectiveness of teriparatide in the ALAFOS regions and are consistent with other studies showing reduction of fractures after 6 months of teriparatide treatment. These results should be interpreted in the context of the noncontrolled design of this observational study.