bluuebunny/crossref_metadata_2025 huggingface dataset:
Reapproaching Old Treatments: Considerations for PK/PD Studies on Phage Therapy for Bacterial Respiratory Infections
Authors: Schmalstig Alan A. , Freidy Soha , Hanafin Patrick O. , Braunstein Miriam , Rao Gauri G.
Published: February 2021

Antibiotic resistant bacterial respiratory infections are a significant global health burden, and new therapeutic strategies are needed to control the problem. For bacterial respiratory infections, this need is emphasized by the rise in antibiotic resistance and a lean drug development pipeline. Bacteriophage (phage) therapy is a promising alternative to antibiotics. Phage are viruses that infect and kill bacteria. Because phage and antibiotics differ in their bactericidal mechanisms, phage are a treatment option for antibiotic‐resistant bacteria. Here, we review the history of phage therapy and highlight recent preclinical and clinical case reports of its use for treating antibiotic‐resistant respiratory infections. The ability of phage to replicate while killing the bacteria is both a benefit for treatment and a challenge for pharmacokinetic (PK) and pharmacodynamic (PD) studies. In this review, we will discuss how the phage lifecycle and associated bidirectional interactions between phage and bacteria can impact treatment. We will also highlight PK/PD considerations for designing studies of phage therapy to optimize the efficacy and feasibility of the approach.
A Refined Protocol for Coronary Artery Ligation in the Neonatal Mouse
Authors: De Villiers Carla , Riley Paul R.
Published: February 2021

The neonatal mouse heart can regenerate following myocardial infarction (MI), a capacity that is lost after 7 days, providing a model system to study tissue regeneration and the transition to adult wound healing. MI can be induced in neonatal mice surgically by coronary artery ligation. In this protocol, neonates are anesthetized using a combination of inhaled isoflurane anesthesia and induced hypothermia, a significant ethical refinement over previous protocols. A lateral thoracotomy is performed, and an 8‐0 suture is used to ligate an area below the left atrium to induce MI. The ribs and skin are closed using 7‐0 sutures, and the pup is rapidly rewarmed with a supply of oxygen. Once recovered, the pup is cleaned and rolled in a fecal bath to mask the smell of surgical interference before being returned to the mother. The surgical procedure is expected to take 10 to 15 min per pup, with a further 5 min for recovery. A dedicated assistant for recovery of pups is recommended to streamline the procedure. © 2021 Wiley Periodicals LLC.

This article was corrected on 19 July 2022. See the end of the full text for details.
Improving the identification of haploid maize seeds using convolutional neural networks
Authors: Sabadin Felipe , Galli Giovanni , Borsato Ronaldo , Gevartosky Raysa , Campos Gabriela Romêro , Fritsche‐Neto Roberto
Published: February 2021

A critical step toward the success of the doubled haploid (DH) technique is the haploid identification within induction crosses. The R1‐nj marker is the principal mechanism employed in this task enabling the selection of haploids at the seed stage. Although it seems easy to identify haploid seeds, this task is performed manually by visual classification, which becomes an inefficient process in terms of time and labor. Also, differential phenotypic expression of the R1‐nj marker results in high rates of false positives among haploid seeds. For the first time, an image‐based convolutional neural network (CNN) was trained to identify true positives among putative haploid seeds. The experiment was conducted using 3,000 maize (Zea mays L.) seeds from induction crosses classified as haploid (1,000), diploid (1,000), and inhibited (1,000) class. Images were taken from each seed, and then seeds were planted in the field to confirm their ploidy. For putative haploids (R1‐nj phenotype), the classification accuracy on average was 94.39%, 97.07% for the haploid class, and 91.71% for the diploid class. However, the CNN model was unable to distinguish true haploid seeds among the putative haploid class, which indicates that CNN did not recognize different patterns between them. Finally, we provided a highly accurate and trained CNN model to the scientific community to classify haploid maize seeds via R1‐nj, which can support maize breeders to optimize DH pipelines, mainly for small breeding programs with limited resources.
Microscale Ionic Diodes: An Overview
Authors: Riza Putra Budi , Tshwenya Luthando , Buckingham Mark A. , Chen Jingyuan , Jeremiah Aoki Koichi , Mathwig Klaus , Arotiba Omotayo A. , Thompson Abigail K. , Li Zhongkai , Marken Frank
Published: February 2021

Ionic rectifier membranes or devices generate uni‐directional ion transport to convert an alternating current (AC) ion current input into stored energy or direct current (DC) in the form of ion/salt gradients. Electrochemical experiments 80 years ago were conducted on biological membrane rectifier systems, but today a plethora of artificial ionic rectifier types has been developed and electroanalytical tools are employed to explore mechanisms and performance. This overview focuses on microscale ionic rectifiers with a comparison to nano‐ and macroscale ionic rectifiers. The potential is surveyed for applications in electrochemical analysis, desalination, energy harvesting, electrochemical synthesis, and in selective ion extraction.
Degradation of Polymer Solar Cells: Knowledge Learned from the Polymer:Fullerene Solar Cells
Authors: Yan Lingpeng , Ma Chang-Qi
Published: February 2021

Although power conversion efficiency (PCE) of polymer solar cells (PSCs) has exceeded 18%, the lifetime of PSCs is far away from satisfactory and has become the most critical issue before the commercialization of PSCs. Understanding the degradation mechanism and finding the proper way to suppress the degradation process are of high interests for PSC research. Polymer:fullerene solar cells (PFSCs) have a long research history and the working principle is well‐understood, so they are good models for the degradation mechanism study. This mini‐review summarizes the latest research progress of the PFSCs’ degradation studies. Based on the results achieved, one can identify the extrinsic and intrinsic stress factors that cause different degradation processes. Degradation pathways of the PFSCs at different positions in the cells will be discussed in detail, including the electrode, the buffer layer, and the photoactive layer. Special emphasis will be put on various degradation processes of the photoactive layers. In the meantime, the methods to suppress the degradation processes will be presented accordingly. This mini‐review gives a comprehensive insight into the degradation mechanism and stability‐improvement strategies of PFSCs, which has important guiding significance for the stability‐improvement research of PSCs.
Blockchain mechanism with Byzantine fault tolerance consensus for Internet of Drones services
Authors: Singh Jaya , Venkatesan S.
Published: February 2021

The increasing number of drones brings various issues like security risks, increasing air traffic, misuse or crash of drones, and so on. Blockchain can provide the solution to mitigate these problems of drones. Hence, in this article, we have presented the Blockchain of Drones (BCoD), a conceptual approach of collaboration between blockchain and IoD to make drones advantageous through blockchain properties. But the main challenge for adopting blockchain is scalability as consensus in blockchain relies on the message communications by replicated nodes to attain flexibility against faulty nodes. Considering this, we present an advanced byzantine fault tolerance (ABFT) consensus for drone‐based applications. This protocol provides scalability with minimum cost and resources for achieving general agreement. It uses only f + 1 resources in normal case and 2f + 1 resources in faulty case with O(n) communication complexity. The systematic analysis and evaluation show that the ABFT improves the performance of the system for a wide range of networks compared with existing BFT systems.
Limited knowledge and distrust are important social factors of out‐patient’ s ‘inappropriate diagnosed seeking behaviour’: a qualitative research in Shanghai
Authors: Ruan Yuhui , Zhuang Chenyang , Chen Weisin , Xie Jinyu , Zhao Yaodong , Zhang Lufa , Lin Hong
Published: February 2021

Aims

This study is designed to present out‐patient's ‘inappropriate diagnosed seeking behaviour’ in tertiary hospitals and interpret its association with some potential social factors.

Methods

A qualitative study based on grounded theory was designed in this paper. The participates were recruited by a two‐stage process. The field observation and in‐depth interview were adopted for data collection. Multi‐round (five rounds) sampling and continuing data analysis were adopted as well.

Results

Totally 26 out‐patients from three tertiary hospitals in Shanghai were involved. Four focused codes, including ‘limited policy‐related knowledge’, ‘limited health‐related knowledge’, ‘distrust on related policy’ and ‘distrust on medical networks’, were identified. Then, a theoretical model about the association of out‐patient's ‘limited knowledge’ with ‘distrust’ and its relationship with ‘inappropriate first‐diagnosed seeking behaviour’ in tertiary hospitals was developed.

Conclusion

‘Inappropriate first‐diagnosed seeking behaviour’ of the out‐patients in tertiary hospitals is closely associated with their limited knowledge and related distrust. Great effort on improving publics' knowledge and rebuilding a benign trust relationship with out‐patients and the medical networks is found to be essential for guiding publics' appropriate first‐diagnosed health behaviour in various levels of medical institutions.
Stabilizing instability‐suboptimality‐and‐chaos‐prone fluctuations at crisis junctures: Stochastic possibilities for crisis management
Authors: Kara Ahmet
Published: February 2021

There is a rich array of ways in which unstable, suboptimal and chaos‐prone fluctuations could appear at crisis junctures. The richness of the patterns associated with such fluctuations presents considerable challenges to the theory of crises as well as the policies targeting various tendencies induced by crises. Dealing with complexly interwoven unstable, suboptimal and potentially chaotic tendencies is not an easy task, which may require new combinations of methods analysing the causal connections and feedback relations embedded in the web of relations characterizing the crisis‐junctures. In this paper, we develop an illustrative dynamic model that takes into account such causally connected feedback relations so as to construct and simulate stochastic policy options, which can influence and help stabilize unstable, suboptimal and chaotic trajectories of exchange rates at financial crisis junctures. For reasons of convenience and practical relevance, we exemplified such policies using taxes. One of the constructed examples makes use a stochastic taxing policy to influence the coefficient of adjustment, which influences the amount of adjustments and hence fluctuations in the market. We incorporate a software‐based optimization setup into the simulation model to find the optimal values of the policy parameter to be used for the purpose of simulating the trajectories of the exchange rates. It turns out that the suggested policies could influence/reduce the fluctuations in the market and hence help stabilize unstable or chaotic exchange rate trajectories. The second example in the paper is concerned with an empirical case relating to a particular financial crisis juncture of Turkey during May–November 2018.
Prioritization of Osteoporosis‐Associated Genome‐wide Association Study (GWAS) Single‐Nucleotide Polymorphisms (SNPs) Using Epigenomics and Transcriptomics
Authors: Zhang Xiao , Deng Hong‐Wen , Shen Hui , Ehrlich Melanie
Published: February 2021

Genetic risk factors for osteoporosis, a prevalent disease associated with aging, have been examined in many genome‐wide association studies (GWASs). A major challenge is to prioritize transcription‐regulatory GWAS‐derived variants that are likely to be functional. Given the critical role of epigenetics in gene regulation, we have used an unusual epigenetics‐based and transcription‐based approach to identify some of the credible regulatory single‐nucleotide polymorphisms (SNPs) relevant to osteoporosis from 38 reported bone mineral density (BMD) GWASs. Using Roadmap databases, we prioritized SNPs based upon their overlap with strong enhancer or promoter chromatin preferentially in osteoblasts relative to 12 heterologous cell culture types. We also required that these SNPs overlap open chromatin (Deoxyribonuclease I [DNaseI]‐hypersensitive sites) and DNA sequences predicted to bind to osteoblast‐relevant transcription factors in an allele‐specific manner. From >50,000 GWAS‐derived SNPs, we identified 14 novel and credible regulatory SNPs (Tier‐1 SNPs) for osteoporosis risk. Their associated genes, BICC1, LGR4, DAAM2, NPR3, or HMGA2, are involved in osteoblastogenesis or bone homeostasis and regulate cell signaling or enhancer function. Four of these genes are preferentially expressed in osteoblasts. BICC1, LGR4, and DAAM2 play important roles in canonical Wnt signaling, a pathway critical for bone formation and repair. The transcription factors predicted to bind to the Tier‐1 SNP‐containing DNA sequences also have bone‐related functions. We present evidence that some of the Tier‐1 SNPs exert their effects on BMD risk indirectly through little‐studied long noncoding RNA (lncRNA) genes, which may, in turn, control the nearby bone‐related protein‐encoding gene. Our study illustrates a method to identify novel BMD‐related causal regulatory SNPs for future study and to prioritize candidate regulatory GWAS‐derived SNPs, in general. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Structural, ultrastructural, and functional aspects of the skin of the upper lip of silver carp (Hypophthalmichthys molitrix)
Authors: Sayed Ramy K. A. , Abd‐El Aziz Nora A. , Ibrahim Ismail A. , Mokhtar Doaa M.
Published: February 2021

This study was carried out to analyze the architecture of the skin of the upper lip region in silver carp fishes using light, scanning, and transmission electron microscopies. The skin was composed of epidermis, dermis, and hypodermis. The epidermis of the upper lip was characterized by the presence of large number of metachromatic mucous goblet cells, which showed positive reaction with Periodic Acid–Schiff (PAS), Alcian blue (AB), and toluidine blue. The electroreceptive lateral line system was organized into ampullary and tuberous organs. The scanning electron microscopy showed that the surface of the skin of upper lip was covered by microridges and characterized by the presence of taste buds and openings of lateral line system. As observed by transmission electron microscopy, the cytoplasm of the epidermal layers appeared electron‐dense except for the superficial layer, where the cytoplasm was electron‐lucent and contained many vacuoles and few profiles of rER. Moreover, the epidermis contained rodlet cells and stem cells. Few organelles were found within the cytoplasm of club cells. Neutrophils and eosinophilic granular cells were also demonstrated as important immune cells in the epidermis of the upper lip. Furthermore, lymphocytes and basophils could be identified with macrophage in the epidermal layer of the upper lip. Numerous telocytes were demonstrated between the collagen fibers of the dermis and bundles of myelinated nerve fibers. In conclusion, the skin of the upper lip region of silver carp displayed many sensory and immunological characteristic features.
Initial assessment in emergency departments by chief complaint and respiratory rate
Authors: Soeno Shoko , Hara Konan , Fujimori Ryo , Hashimoto Katsuhiko , Shirakawa Toru , Sonoo Tomohiro , Nakamura Kensuke , Goto Tadahiro
Published: February 2021

Background

Understanding heterogeneity of the respiratory rate (RR) as a risk stratification marker across chief complaints is important to reduce misinterpretation of the risk posed by outcome events and to build accurate risk stratification tools. This study was conducted to investigate the associations between RR and clinical outcomes according to the five most frequent chief complaints in an emergency department (ED): fever, shortness of breath, altered mental status, chest pain, and abdominal pain.

Methods

This retrospective cohort study examined ED data of all adult patients who visited the ED of a tertiary medical center during April 2018‐September 2019. The primary exposure was RR at the ED visit. Outcome measures were hospitalization and mechanical ventilation use. We used restrictive cubic spline and logistic regression models to assess the association of interest.

Results

Of 16 956 eligible ED patients, 4926 (29%) required hospitalization; 448 (3%) required mechanical ventilation. Overall, U‐shaped associations were found between RR and the risk of hospitalization (eg, using RR = 16 as the reference, the odds ratio [OR] of RR = 32, 6.57 [95% CI 5.87‐7.37]) and between RR and the risk of mechanical ventilation. This U‐shaped association was driven by patients' association with altered mental status (eg, OR of RR = 12, 2.63 [95% CI 1.25‐5.53]). For patients who have fever or shortness of breath, the risk of hospitalization increased monotonously with increased RR.

Conclusions

U‐shaped associations of RR with the risk of overall clinical outcomes were found. These associations varied across chief complaints.
Circulating miR‐181a and miR‐223 expression with the potential value of biomarkers for the diagnosis of systemic lupus erythematosus and predicting lupus nephritis
Authors: Abdul‐Maksoud Rehab S. , Rashad Nearmeen M. , Elsayed Walid S. H. , Ali Manal A. , Kamal Nafesa M. , Zidan Haidy E.
Published: February 2021

Background

MicroRNAs (miRNAs) contribute to the development and progression of systemic lupus erythematosus (SLE) by affecting a wide range of targeted genes and facilitating the development of lupus nephritis (LN). The present study aimed to analyze the serum expression of miR‐181a and miR‐223 in SLE patients and to assess whether they could serve as novel biomarkers for SLE diagnosis and to distinguish LN.

Methods

The study included 70 control subjects and 116 patients with SLE (67 non‐LN and 49 LN groups). Circulating miR‐181a and miR‐223 expression levels were analyzed among the Egyptian population using a real‐time polymerase chain reaction.

Results

Up‐regulation of miR‐181a was detected among SLE patients compared to healthy controls and higher values were reported among the LN group compared to the non‐LN group. Down‐regulation of miR‐223 was reported among SLE patients compared to controls and lower values were reported among the LN group compared to the non‐LN group. The higher miR‐181a expression and the lower miR‐223 expression were associated with higher stages of LN. SLE disease activity index, proteinuria and serum creatinine were independently correlated with miR‐181a and miR‐223 among SLE patients by linear regression analysis. Receiver‐operating characteristic curve analysis revealed that combined miR‐181a and miR‐223 expression increased the sensitivity and specificity for the diagnosis of SLE and further distinguished LN from non‐LN patients.

Conclusions

miR‐181a and miR‐223 could play a role in evaluating SLE disease progression and prognosis. Combined miR‐181a and miR‐223 expression analysis could serve as novel serum‐based biomarkers in the diagnosis of SLE and predicting LN among Egyptians.
A new interpretation of nonpulmonary vein substrates of the left atrium in patients with atrial fibrillation
Authors: Rillo Mariano , Palamà Zefferino , Punzi Raffaele , Vitanza Salvatore , Aloisio Angelo , Polini Silvia , Tucci Antonella , Pollastrelli Annalisa , Zonno Francesco , Anastasia Antonio , Giannattasio Cesare Franco , My Luigi
Published: February 2021

Background

Substrate analysis of the left atrium in patients undergoing atrial fibrillation ablation has limitations when performed by means of simple bipolar acquisition.

Objective

To evaluate the incidence of low‐voltage zones (LVZs) through maps constructed by means of various catheters: multipolar (MC), omnipolar (OC), and circular catheters (CMCs) with the 3D electro‐anatomical systems (3d‐S) CARTO3 and EnSite Precision.

Methods

To assess LVZs, we acquired maps by means of CMC and MC in the voltage range 0.05‐0.5 mV in 70 consecutive patients in sinus rhythm. In the case of OC only, we made an intra‐patient comparison of bipolar maps constructed by means of the along and across, and HD‐Wave configurations of the EnSite 3d‐S in the ranges of 0.05‐0.5 and 0.5‐1.0 mV. On the basis of this comparison, we chose the range that best identified LVZs as a set of different colors (SDC) compatible with patchy fibrosis (qualitative analysis). Subsequently, we detected the voltage values corresponding to purple and gray points, close to SDC, and the value inside corresponding to blue, green, and red colors, and we evaluated the color change in other voltage ranges. Finally, we performed a quantitative analysis of LVZs by applying the qualitative characteristics described above.

Results

On the basis of our settings, for OC, the optimal range identifying LVZs was 0.3‐0.6 mV. OC revealed smaller LVZs than MC (P < .05 or P < .001), except in the lateral wall. No significant differences were observed between CMCs.

Conclusions

In our experience, OC does not present the limits of bipolar HD maps, though further studies are needed in order to confirm that 0.3‐0.6 mV is the optimal voltage range within which to identify LVZs.
Evidence for centennial‐scale Lateglacial and early Holocene climatic complexity from Quoyloo Meadow, Orkney, Scotland
Authors: Timms Rhys G. O. , Abrook Ashley M. , Matthews Ian P. , Francis Christopher P. , Mroczkowska Agnieszka , Candy Ian , Brooks Stephen J. , Milner Alice M. , Palmer Adrian P.
Published: February 2021

The influence of the North Atlantic on the margins of Europe means the region is particularly sensitive to changes in the ocean–atmospheric system. During the Last Glacial–Interglacial Transition (16–8 cal ka bp) this system was repeatedly disrupted, leading to a series of abrupt and short‐lived shifts in climate. Despite much research, the number and magnitude of these ‘centennial‐scale’ events is not well understood. To address this, we expand upon investigations at Quoyloo Meadow, Orkney, Scotland, one of the best chronologically constrained palaeoclimate records in northern Britain. By coupling stable isotope and chironomid fossil analyses with existing data, this study identifies multiple phases of centennial‐scale disturbance at: c. 14.0, 11.1, 10.8, 10.5, 10.45 and 10.3 cal ka bp, with the events at 14.0 and 10.3 exhibiting a particularly pronounced cold‐climate signature. During the Holocene, the strongest response to climate forcing was at c. 10.3–10.0 cal ka bp, expressed as a two‐stage drop in mean July temperatures, a shift in pollen spectra indicative of ‘less‐stable’ climatic regimes, and a depletion in δ18O values. We interpret this as the first reliably dated incidence of the ‘10.3‐ka event’ in the British Isles and consider the wider impact of this climatic reversal in other Holocene records.
Whatʼs in this drink? Classification and adulterant detection in Irish Whiskey samples using near infrared spectroscopy combined with chemometrics
Authors: Power Aoife C , Jones John , NiNeil Caoimhe , Geoghegan Sive , Warren Susan , Currivan Sinead , Cozzolino Daniel
Published: February 2021

BACKGROUND

Near‐infrared (NIR) spectroscopy coupled with principal component analysis (PCA) and partial least squares (PLS) regression was used to analyse a series of different Irish Whiskey samples in order to define their spectral profile and to assess the capability of the NIR method to identify samples based on their origin and storage (e.g. distiller, method of maturation). The ability of NIR spectroscopy to quantify the level of potential chemical adulterants was also investigated. Samples were spiked with 0.1%, 0.5%, 1.0%, 1.5% and 2.0% v/v of each adulterant (e.g. methanol, ethyl acetate, etc.) prior to NIR analysis.

RESULTS

The results of this study demonstrated the capability of NIR spectroscopy combined with PLS regression to classify the whiskey samples and to determine the level of adulteration. Moreover, the potential of NIR coupled with chemometric analysis as a rapid, portable, and non‐destructive screening tool for quality control, traceability, and food/beverage adulteration for customs and other regulatory agencies, to mitigate beverage fraud was illustrated.

CONCLUSION

Given the non‐specificity of the NIR technique, these positive preliminary results indicated that this method of analysis has the potential to be applied to identify the level of adulteration in distilled spirits. The rapid nature of the technique and lack of consumables or sample preparation required allows for a far more time and cost‐effective analysis per sample. © 2021 Society of Chemical Industry.
The depletion of Circ‐PRKDC enhances autophagy and apoptosis in T‐cell acute lymphoblastic leukemia via microRNA‐653‐5p/Reelin mediation of the PI3K/AKT/mTOR signaling pathway
Authors: Ling Zhang , Fang Zhi‐Gang , Wu Jie‐Yong , Liu Jia‐Jun
Published: February 2021

A range of circular (Circ) RNAs have been demonstrated to be of therapeutic significance for the treatment of acute lymphoblastic leukemia (ALL). Here, we investigated the mechanisms underlying the action of Circ‐PRKDC and the microRNA‐653‐5p/Reelin (miR‐653‐5p/RELN) axis in T‐cell ALL (T‐ALL).Clinical specimens were obtained from patients with T‐ALL (n = 39) and healthy controls (n = 30). In each specimen, we determined the expression levels of Circ‐PRKDC, miR‐653‐5p, and RELN. Human T‐ALL cells (Jurkat) were transfected with Circ‐PRKDC‐ or miR‐653‐5p‐related sequences to investigate cell proliferation, apoptosis, and autophagy. We also determined the levels of Circ‐PRKDC, miR‐653‐5p, RELN, and signaling proteins related to phosphoinositide 3‐kinase (PI3K), AKT, and mammalian target of rapamycin (mTOR). Finally, we decoded the interactions between Circ‐PRKDC, miR‐653‐5p, and RELN. The expression levels of Circ‐PRKDC and RELN were upregulated in T‐ALL tissues and cells while the levels of miR‐653‐5p were downregulated. Thereafter, then silencing of Circ‐PRKDC, or the enforced expression of miR‐653‐5p, repressed the expression of RELN and the activation of the PI3K/AKT/mTOR signaling pathway, thus enhancing cell autophagy and apoptosis, and disrupting cell proliferation. Circ‐PRKDC acted a sponge for miR‐653‐5p while miR‐653‐5p targeted RELN. The knockdown of miR‐653‐5p abrogated the silencing of Circ‐PRKDC‐induced effects in T‐ALL cells. The depletion of Circ‐PRKDC elevated miR‐653‐5p to silence RELN‐mediated PI3K/AKT/mTOR signaling activation, thereby enhancing autophagy and apoptosis in T‐ALL cells.
Cryosurgical Ablation for Treatment of Rhinitis: Two‐Year Results of a Prospective Multicenter Study
Authors: Ow Randall A. , O'Malley Ellen M. , Han Joseph K. , Lam Kent K. , Yen David M.
Published: February 2021

Objectives/Hypothesis

To assess the long‐term (12–24 months) safety and effectiveness of cryoablation of the posterior nasal nerve as treatment for chronic rhinitis.

Study Design

A multicenter, prospective, single‐arm clinical study.

Methods

The study was conducted from February 2017 to April 2020. Study endpoints included change from baseline in the reflective Total Nasal Symptom Score (rTNSS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), physician assessment of improvement using the Clinical Global Impression–Improvement (CGI–I), and the incidence of treatment‐related adverse events.

Results

Ninety‐one participants completed the study through the initial 12‐month study period. Sixty‐two participants consented to the long‐term follow‐up with 57 completing the 24‐month follow‐up. Significant improvements in the total rTNSS were reflected in a median change from baseline of −3.0 or −4.0 at all timepoints (P < .001). Greater than 80.0% of participants achieved the minimum clinically important difference (MCID) of improvement by ≥1 point on the rTNSS at all follow‐ups. Total RQLQ scores indicated significant improvement (P < .0001) in quality of life. Over 77% of participants achieved the MCID (≥0.5 points) for the total RQLQ score. According to the CGI–I, ≥83.0% experienced improvement at all but the 12‐month visit (61.9%). One participant experienced two treatment‐related serious adverse events (epistaxis and retained pledget). A total of 29 nonserious treatment‐related AEs were reported in 23 participants; most events were transient and resolved with little to no intervention.

Conclusions

Cryotherapy significantly and clinically improves rhinitis symptoms and quality of life with outcomes that are durable through 24 months after treatment.

Level of Evidence

4 Laryngoscope, 131:1952–1957, 2021
Highly Thermal‐Resistant and Biodegradable Textile Sizes from Glycols Modified Soy Proteins for Remediation of Textile Effluents
Authors: Xing Bin , Xu Xiaoyun , Hu Wenfeng , Ni Ruiyan , Zhao Yi
Published: February 2021

Poly(vinyl alcohol) (PVA) sizes are widely used in textile industry due to their excellent sizing properties on synthetic fibers and their blends. However, PVA contains non‐biodegradable chemicals and is a major contributor to environmental pollution related to the textile industry. To overcome this problem, an environmental‐benign and highly thermal‐resistant yarn coating is fabricated from soy proteins, an agricultural byproduct. The soy proteins are chemically modified by glycols having varying chain lengths and number of hydroxyl groups. Compared with the physically modified soy proteins and their sized yarns, coating made from the soy proteins esterified by 1,4‐butanediol show 91.38% increment in work of rupture at 120 °C and cotton/polyester (65/35) yarns sized by 1,4‐butanediol esterified soy protein sizes have 39.91% decrease in coefficient of friction. In addition, 1,4‐butanediol esterified soy sizes have a five‐day biochemical oxygen demand/chemical oxygen demand of 0.476, indicating that the chemically modified soy sizes have high biodegradability in activated sludge. Successful utilization of modified soy sizes can promote large‐quantity applications of soy byproducts, impelling high value addition to agricultural byproducts and sustainability of textile industry.
Proton Conductive Membranes from Covalently Cross‐Linked Poly(Acrylate)/Silica Interpenetrating Networks
Authors: Zhyhailo Mariia , Horechyy Andriy , Meier‐Haack Jochen , Formanek Petr , Malanin Mikhail , Arnhold Kerstin , Schneider Konrad , Yevchuk Iryna , Fery Andreas
Published: February 2021

The preparation of hybrid proton conductive membranes that comprise of covalently linked interpenetrating polymer and inorganic networks is reported. The hybrid membranes are synthesized via simultaneous photo‐initiated polymerization and sol–gel processing. The simultaneous processing permeates fabrication of the membranes that comprises covalently cross‐linked polymeric and inorganic networks. The membranes are characterized by attenuated total reflectance‐Fourier transform infrared spectroscopy, scaning electron microsopy, thermogravimetric analysis, differential scanning calorimetry, in order to confirm their chemical composition, structure, and morphology. An addition of 3‐methacryloxypropyl trimethoxysilane into the sol–gel composition allows the formation of covalent linkages between polymeric and inorganic networks, which facilitates a uniform distribution of the molecular components across the fabricated membranes. The incorporation of the silica network leads to an increase in water retention and proton conductivity of hybrid membranes as compared to their purely polymeric analogues.
End‐Pulled Translocation of a Star Polymer Out of a Confining Cylindrical Cavity
Authors: Tilahun Mesay , Tatek Yergou B.
Published: February 2021

A Langevin dynamics computer simulation is carried out to study the translocation of a single homogeneous star polymer out of a cylindrical cavity connected to a membrane wall with a circular nanopore along the tube axis. The ejection process is driven through an external pulling force applied on the free end monomer of the chain leading arm. The results show that, for a given chain mass and for relatively narrow pores, the mean translocation time 〈τ〉 exhibits a non‐monotonic dependence on the chain functionality f with the existence of a minimum at a critical functionality that defines a boundary between two distinct translocation regimes. Moreover, for a given functionality, the variations of the mean translocation time with respect to the chain mass and the magnitude of the pulling force respectively, are both found to follow a power law relationship. Finally, it has been demonstrated that the translocation dynamics can be significantly altered by changing the confining tube dimensions, with the existence of an optimal tube aspect ratio that minimizes the chain mean translocation time 〈τ〉.
Profiling the Biochemical Signature of GBA‐Related Parkinson's Disease in Peripheral Blood Mononuclear Cells
Authors: Avenali Micol , Cerri Silvia , Ongari Gerardo , Ghezzi Cristina , Pacchetti Claudio , Tassorelli Cristina , Valente Enza Maria , Blandini Fabio
Published: February 2021

Background

GBA mutations are the commonest genetic risk factor for Parkinson's disease (PD) and also impact disease progression.

Objective

The objective of this study was to define a biochemical profile that could distinguish GBA‐PD from non‐mutated PD.

Methods

29 GBA‐PD, 37 non‐mutated PD, and 40 controls were recruited; α‐synuclein levels in plasma, exosomes, and peripheral blood mononuclear cells were analyzed, GCase and main GCase‐related lysosomal proteins in peripheral blood mononuclear cells were measured.

Results

Assessment of plasma and exosomal α‐synuclein levels did not allow differentiation between GBA‐PD and non‐mutated PD; conversely, measurements in peripheral blood mononuclear cells clearly distinguished GBA‐PD from non‐mutated PD, with the former group showing significantly higher α‐synuclein levels, lower GCase activity, higher LIMP‐2, and lower Saposin C levels.

Conclusion

We propose peripheral blood mononuclear cells as an easily accessible and manageable model to provide a distinctive biochemical profile of GBA‐PD, potentially useful for patient stratification or selection in clinical trials. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Make a Left Turn: Cortico‐Striatal Circuitry Mediating the Attentional Control of Complex Movements
Authors: Sarter Martin , Avila Cassandra , Kucinski Aaron , Donovan Eryn
Published: February 2021

Background

In movement disorders such as Parkinson's disease (PD), cholinergic signaling is disrupted by the loss of basal forebrain cholinergic neurons, as well as aberrant activity in striatal cholinergic interneurons (ChIs). Several lines of evidence suggest that gait imbalance, a key disabling symptom of PD, may be driven by alterations in high‐level frontal cortical and cortico‐striatal processing more typically associated with cognitive dysfunction.

Methods

Here we describe the corticostriatal circuitry that mediates the cognitive–motor interactions underlying such complex movement control. The ability to navigate dynamic, obstacle‐rich environments requires the continuous integration of information about the environment with movement selection and sequencing. The cortical‐attentional processing of extero‐ and interoceptive cues requires modulation by cholinergic activity to guide striatal movement control. Cue‐derived information is “transferred” to striatal circuitry primarily via fronto‐striatal glutamatergic projections.

Result

Evidence from parkinsonian fallers and from a rodent model reproducing the dual cholinergic–dopaminergic losses observed in these patients supports the main hypotheses derived from this neuronal circuitry‐guided conceptualization of parkinsonian falls. Furthermore, in the striatum, ChIs constitute a particularly critical node for the integration of cortical with midbrain dopaminergic afferents and thus for cues to control movements.

Conclusion

Procholinergic treatments that enhance or rescue cortical and striatal mechanisms may improve complex movement control in parkinsonian fallers and perhaps also in older persons suffering from gait disorders and a propensity for falls. © 2021 International Parkinson and Movement Disorder Society
Tailoring the strength and number of halogen bonds toward room temperature phosphorescent micro‐cocrystals
Authors: Yu Panpan , Li Yang , Zhen Yonggang , Dong Huanli , Hu Wenping
Published: February 2021

Organic room temperature phosphorescent materials are very limited to date. Halogen bonding interactions not only promote the intersystem crossing process, but also act as cement and dilute solution, preventing the aggregation induced quenching. Herein, four cocrystals using phenazine (PhZ) as halogen‐bonded acceptor and 1,2,4,5‐tetrabromo‐3,6‐diiodobenzene (BrFB) or 1,2,4,5‐tetrafluoro‐3,6‐diiodobenzene (IFB) as halogen‐bonded donor have been successfully synthesized in definite stoichiometric ratio (PhZ : XFB = 1:1 and 2:1) through simple solvent evaporation method. Among the four cocrystals, the halogen bonding interactions play an important role in assembling properties and the large red spots on Hirshfeld surface imply the strong strength. Notably, the IFB‐PhZ cocrystals exhibit a phosphorescence emission at peak of 733 nm with a lifetime up to 159 µs. The results further suggest the importance of the strength and number of halogen bonds to design organic room temperature phosphorescent materials.
Obesity‐Associated Myeloid Immunosuppressive Cells, Key Players in Cancer Risk and Response to Immunotherapy
Authors: Sanchez‐Pino Maria Dulfary , Gilmore Linda Anne , Ochoa Augusto C. , Brown Justin C.
Published: February 2021

Obesity is a risk factor for developing several cancers. The dysfunctional metabolism and chronic activation of inflammatory pathways in obesity create a milieu that supports tumor initiation, progression, and metastasis. Obesity‐associated metabolic, endocrine, and inflammatory mediators, besides interacting with cells leading to a malignant transformation, also modify the intrinsic metabolic and functional characteristics of immune myeloid cells. Here, the evidence supporting the hypothesis that obesity metabolically primes and promotes the expansion of myeloid cells with immunosuppressive and pro‐oncogenic properties is discussed. In consequence, the accumulation of these cells, such as myeloid‐derived suppressor cells and some subtypes of adipose‐tissue macrophages, creates a microenvironment conducive to tumor development. In this review, the role of lipids, insulin, and leptin, which are dysregulated in obesity, is emphasized, as well as dietary nutrients in metabolic reprogramming of these myeloid cells. Moreover, emerging evidence indicating that obesity enhances immunotherapy response and hypothesized mechanisms are summarized. Priorities in deeper exploration involving the mechanisms of cross talk between metabolic disorders and myeloid cells related to cancer risk in patients with obesity are highlighted.
Real-World Characteristics, Treatment Patterns, Health Care Resource Use, and Costs of Patients with Diffuse Large B-Cell Lymphoma in the U.S
Authors: Yang Xiaoqin , Laliberté François , Germain Guillaume , Raut Monika , Duh Mei Sheng , Sen Shuvayu S. , Lejeune Dominique , Desai Kaushal , Armand Philippe
Published: February 2021

Background

Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin lymphoma in the U.S., but current real-world data are limited. This study was conducted to describe real-world characteristics, treatment patterns, health care resource utilization (HRU), and health care costs of patients with treated DLBCL in the U.S.

Materials and Methods

A retrospective study was conducted using the Optum Clinformatics Data Mart database (January 2013 to March 2018). Patients with an International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis for DLBCL after October 2015 and no prior International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis for unspecified DLBCL or primary mediastinal large B-cell lymphoma were classified as incident; those with such codes were classified as prevalent. An adapted algorithm identified lines of therapy (e.g., first line [1L]). All-cause HRU and costs were calculated per-patient-per-year (PPPY) among patients with a ≥1L.

Results

Among 1,877 incident and 651 prevalent patients with ≥1L, median age was 72 years and 46% were female. Among incident patients, 22.6% had at least two lines (2L), whereas 38.4% of prevalent patients had ≥2L. The most frequent 1L therapy was rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Incident patients had 1.3 inpatient and 42.0 outpatient (OP) visits PPPY, whereas prevalent patients had 0.8 and 31.3 visits PPPY, respectively. Total costs were $137,156 and $81,669 PPPY for incident and prevalent patients, respectively. OP costs were the main driver of total costs at $88,202 PPPY, which were higher within the first year.

Conclusion

This study showed that a large portion of patients require additional therapy after 1L treatment to manage DLBCL and highlighted the substantial economic burden of patients with DLBCL, particularly within the first year following diagnosis.

Implications for Practice

Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) carry a substantial clinical and economic burden. A large portion of these patients require additional therapy beyond first-line treatment. There is significant unmet need among patients with DLBCL who require additional therapy beyond first-line treatment. Patients who do not respond to first-line therapy and are not eligible for transplants have very high health care resource utilization and costs, especially in the first 12 months following initiation of treatment.
Study on UV/sunlight curable self‐healing topological polysulfide polymer network based on disulfide exchange
Authors: Fu Qi , Yan Qiming , Zhou Meng , Xie Weidi , Fu Heqing
Published: February 2021

Thiol‐ene click reaction is widely used in polymer chemistry due to its high efficiency and regioselectivity, and disulfide exchange can endow a covalently crosslinked network with self‐healing property. In order to explore the feasibility of introducing disulfide bonds into the polymer network via thiol‐ene click reaction, first, a nine‐function ene‐terminated dendrimer (NETD) was synthesized. Then, the polysulfide dithiol (PSDT) was used as a crosslinker to form the topological polysulfide polymer network (PSPN) under UV light/sunlight. The topological PSPN exhibited outstanding self‐healing property at moderate temperature and recovery of mechanical strength. This result was achieved by the exchangeable disulfide links in the network, leading to renewal of crosslinks across the damaged surface.
Interfacial improvements in cellulose nanofibers reinforced polylactide bionanocomposites prepared by in situ reactive extrusion
Authors: Li Feng‐Jiao , Yu Xi‐Tong , Huang Zan , Liu Ding‐Fu
Published: February 2021

Grafting of polylactide (PLA) onto the cellulose nanofiber (CNF) (CNF‐g‐PLA) was prepared by in situ reactive extrusion using dicumyl peroxide (DCP) as a free radical initiator to improve the interfacial adhesion between CNFs and PLA. The effect of DCP content on the dynamic rheological properties, crystallization behavior, mechanical properties, and micromorphology of PLA/CNF (95/5) bionanocomposite was systematically investigated. FTIR spectra confirmed that PLA chains were successfully grafted onto the CNF surface by forming CC bonds. The presence of such CC crosslinks improved stress transfer at the CNF–PLA interface; SEM and TEM observations and adhesion factor calculated from DMA data confirmed that the synthesized graft copolymers improved the interfacial interaction between CNFs and PLA matrix, thus enhancing the mechanical properties of CNF‐g‐PLA nanocomposites. Compared with PLA/CNF (95/5) bionanocomposite, the maximum tensile modulus, tensile strength, elongation at break, and V‐notched Izod impact strength of CNF‐g‐PLA nanocomposites were increased by 31.8%, 20.0%, 12.0%, and 27.9%, respectively. WAXD and DSC analyses indicated that the crystallinity degree of the grafted CNF‐g‐PLA was higher than that of PLA/CNF (95/5) bionanocomposite, and first increased and then decreased with increasing DCP content. The polarized optical micrographs confirmed that DCP‐initiated grafting significantly increased the nucleation density but decreased the spherulite size of PLA. The melt strength of CNF‐g‐PLA nanocomposites was improved due to stronger intermolecular interaction by grafting. This one‐step in situ reactive extrusion technology provides an efficient and economical way to enhance the properties of PLA/CNF bionanocomposites.
A New ‘Hera’ in Hyperspectral Imaging
Authors: Preda Fabrizio , Perri Antonio , Polli Dario
Published: February 2021

Hera Iperspettrale is a novel hyperspectral camera based on a patented Fourier‐transform approach. The device can be employed in a large variety of applications, ranging from cultural heritage to biology, from material sorting and food inspection to remote sensing and vegetation studies. The exceptional throughput of the optical system ensures high‐quality data even at the lowest light dose, making the camera very suitable for fluorescence hyper‐spectral imaging.
MIR Spectroscopy: The Medical Diagnosis Swiss Knife?
Authors: Tariel Hugues , Sire Olivier
Published: February 2021

For more than two decades, mid‐infrared (MIR) spectroscopy appeared a promising method for fast medical diagnostics. However, some material limitations slowed down its development until the past five years. Now, the first CE‐marked diagnosis solutions are coming onto the market and the future of this technology as a near‐patient fast screening test looks bright.
Application of spectral library prediction for parallel reaction monitoring of viral peptides
Authors: Grossegesse Marica , Nitsche Andreas , Schaade Lars , Doellinger Joerg
Published: February 2021

A major part of the analysis of parallel reaction monitoring (PRM) data is the comparison of observed fragment ion intensities to a library spectrum. Classically, these libraries are generated by data‐dependent acquisition (DDA). Here, we test Prosit, a published deep neural network algorithm, for its applicability in predicting spectral libraries for PRM. For this purpose, we targeted 1529 precursors derived from synthetic viral peptides and analyzed the data with Prosit and DDA‐derived libraries. Viral peptides were chosen as an example, because virology is an area where in silico library generation could significantly improve PRM assay design. With both libraries a total of 1174 precursors were identified. Notably, compared to the DDA‐derived library, we could identify 101 more precursors by using the Prosit‐derived library. Additionally, we show that Prosit can be applied to predict tandem mass spectra of synthetic viral peptides with different collision energies. Finally, we used a spectral library predicted by Prosit and a DDA library to identify SARS‐CoV‐2 peptides from a simulated oropharyngeal swab demonstrating that both libraries are suited for peptide identification by PRM. Summarized, Prosit‐derived viral spectral libraries predicted in silico can be used for PRM data analysis, making DDA analysis for library generation partially redundant in the future.