bluuebunny/crossref_metadata_2025 huggingface dataset:
U(‐Th)–Pb age and petrogenesis of Shigar leucogranites, Karakoram Metamorphic Complex, North Pakistan
Authors: Awais Muhammad , Liu Xiao‐Chi , Qasim Muhammad , Wu Fu‐Yuan
Published: July 2022

The Shigar valley of northern Pakistan is a well‐known region for holding a variety of gemstones. As the gemstone‐bearing rock, post‐collisional leucogranites, and pegmatites in Shigar valley have been sporadically researched but the detailed and updated timing record along with the source rocks were not adequate. Here, we present comprehensive U(‐Th)Pb ages, mineral, and whole‐rock isotopic analyses to investigate the petrogenetic evolution of these granitoids. The zircon, xenotime, and monazite U(‐Th)–Pb ages show crystallization of leucogranites that spanned as recent as ~7–3 Ma. The REEs with nearly smooth patterns and distinct negative Eu anomalies in all the leucogranites and pegmatites with contrasting negative Eu anomalies illustrate significantly plagioclase fractionation. These leucogranites and pegmatites have high SiO2 content showing peraluminous geochemistry. Zircon Hf isotopic composition of leucogranites, pegmatites and gneisses have εHf(t) values of −28.4 to +7.4, −24.0 to −16.5, and −13.2 to +1.8, respectively, which shows crustal origin along with the probable contamination from Kohistan‐Ladakh Arc at depths. Furthermore, monazite Nd isotopic composition of leucogranites, pegmatites, and gneisses have εNd(t) values of −22.9 to −9.5, −25.1 to −22.8, and −26.3 to −24.8, which seems purely from crustal source. The whole‐rock Sr‐Nd‐Hf isotopic composition shows that leucogranites and gneisses have 87Sr/86Sr(i) values of 0.71603 to 0.92518, εNd(t) values of −22.2 to −2.7, and εHf(t) values of −44.1 to −0.2, respectively, that also confines it to the metapelitic origin. Our results overall reveal that the leucogranites are produced mainly by the partial melting of Dassu felsic gneiss from the Karakoram Metamorphic Complex, showing signatures of the upper crustal rocks of the subducting Indian Plate and hybridized juvenile Asian crust. The input of heat for partial melting is likely to be derived either from the lithospheric mantle which followed the slab break‐off or from shear heating along Main Karakoram Thrust. Furthermore, a leucogranite sample yielded a zircon U–Pb age of 84.9 Ma, and monazite U(‐Th)–Pb age of 10.8 Ma. The in‐situ zircon Hf and monazite Nd isotopes yielded εHf(t) values of +3.6 to +10.7, and εNd(t) values of +1.0 to +2.4, whereas the whole‐rock 87Sr/86Sr(i) value is 0.70522, εNd(t) is +1.1, and εHf(t) is +4.8, respectively, which confirms it to be sourced from the nearby Kohistan‐Ladakh Arc.
The LncRNA AK018453 regulates TRAP1/Smad signaling in IL‐17‐activated astrocytes: A potential role in EAE pathogenesis
Authors: Zhang Qingxiu , Yang Ying , Chen Yingyu , Wang Yifan , Qin Suping , Lv Ruixue , Zhou Menglu , Yu Qian , Li Xiangyang , Li Xiaocui , Wang Xiaotian , You Hongjuan , Wang Yugang , Zhou Feng , Liu Xiaomei
Published: July 2022

The pro‐inflammatory cytokine interleukin 17 (IL‐17), that is mainly produced by Th17 cells, has been recognized as a key regulator in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Reactive astrocytes stimulated by proinflammatory cytokines including IL‐17 are involved in blood brain barrier destruction, inflammatory cells infiltration and spinal cord injury. However, the role of long non‐coding RNAs (lncRNAs) induced by IL‐17 in the pathogenesis of MS and EAE remains unknown. Herein, we found that an IL‐17‐induced lncRNA AK018453 promoted TGF‐β receptor‐associated protein 1 (TRAP1) expression and Smad‐dependent signaling in mouse primary astrocytes. Knockdown of AK018453 significantly suppressed astrocytosis, attenuated the phosphorylation of Smad2/3, reduced NF‐κB p65 and CBP/P300 binding to the TRAP1 promoter, and diminished pro‐inflammatory cytokine production in the IL‐17‐treated astrocytes. AK018453 knockdown in astrocytes by a lentiviral vector in vivo dramatically inhibited inflammation and prevented the mice from demyelination in the spinal cord during the progression of EAE. Together, these results suggest that AK018453 regulates IL‐17‐dependent inflammatory response in reactive astrocytes and potentially promotes the pathogenesis of EAE via the TRAP1/Smad pathway. Targeting this pathway may have a therapeutic potential for intervening inflammatory demyelinating diseases.
The impact of pubertal DHEA on the development of visuospatial oscillatory dynamics
Authors: Fung Madison H. , Rahman Raeef L. , Taylor Brittany K. , Frenzel Michaela R. , Eastman Jacob A. , Wang Yu‐Ping , Calhoun Vince D. , Stephen Julia M. , Wilson Tony W.
Published: July 2022

The adolescent brain undergoes tremendous structural and functional changes throughout puberty. Previous research has demonstrated that pubertal hormones can modulate sexually dimorphic changes in cortical development, as well as age‐related maturation of the neural activity underlying cognitive processes. However, the precise impact of pubertal hormones on these functional changes in the developing human brain remains poorly understood. In the current study, we quantified the neural oscillatory activity serving visuospatial processing using magnetoencephalography, and utilized measures of dehydroepiandrosterone (DHEA) as an index of development during the transition from childhood to adolescence (i.e., puberty). Within a sample of typically developing youth (ages 9–15), a novel association between pubertal DHEA and theta oscillatory activity indicated that less mature children exhibited stronger neural responses in higher‐order prefrontal cortices during the visuospatial task. Theta coherence between bilateral prefrontal regions also increased with increasing DHEA, such that network‐level theta activity became more distributed with more maturity. Additionally, significant DHEA‐by‐sex interactions in the gamma range were centered on cortical regions relevant for attention processing. These findings suggest that pubertal DHEA may modulate the development of neural oscillatory activity serving visuospatial processing and attention functions during the pubertal period.
Cerebral cortex layer segmentation using diffusion magnetic resonance imaging in vivo with applications to laminar connections and working memory analysis
Authors: Zhang Jie , Sun Zhe , Duan Feng , Shi Liang , Zhang Yu , Solé‐Casals Jordi , Caiafa Cesar F.
Published: July 2022

Understanding the laminar brain structure is of great help in further developing our knowledge of the functions of the brain. However, since most layer segmentation methods are invasive, it is difficult to apply them to the human brain in vivo. To systematically explore the human brain's laminar structure noninvasively, the K‐means clustering algorithm was used to automatically segment the left hemisphere into two layers, the superficial and deep layers, using a 7 Tesla (T) diffusion magnetic resonance imaging (dMRI)open dataset. The obtained layer thickness was then compared with the layer thickness of the BigBrain reference dataset, which segmented the neocortex into six layers based on the von Economo atlas. The results show a significant correlation not only between our automatically segmented superficial layer thickness and the thickness of layers 1–3 from the reference histological data, but also between our automatically segmented deep layer thickness and the thickness of layers 4–6 from the reference histological data. Second, we constructed the laminar connections between two pairs of unidirectional connected regions, which is consistent with prior research. Finally, we conducted the laminar analysis of the working memory, which was challenging to do in the past, and explained the conclusions of the functional analysis. Our work successfully demonstrates that it is possible to segment the human cortex noninvasively into layers using dMRI data and further explores the mechanisms of the human brain.
Optimal hedging in the presence of internal flexibility
Authors: Jiang Jiaqi , Feng Yun
Published: July 2022

Internal flexibility aids in risk management and has a broader application than hedging instruments. This paper demonstrates how optimal hedging policies are affected by it. We develop a dynamic risk management model to capture financial and operational decisions. We first show that internal flexibility reduces the marginal value of hedging instruments. As a result, optimal financial hedging is selective and dependent on investment opportunities. These opportunities account for the majority of the difference between hedged and unhedged firms. By incorporating internal flexibility, the model becomes more realistic but also generates a complex interaction between financial hedging and marketing strategy. During the growth phase, hedging instruments are partially substitutive but have a synergistic effect on investment. In the mature or declining phase, the remedial effect of marketing strategy maintains investment, thereby increasing operating risk and the marginal value of financial hedging. These results are applicable to firms free of agency conflicts and provide a solid theoretical basis for future empirical tests. We advise that scholars thoroughly examine internal flexibility and development stages in the process.
Apolipoprotein E Polymorphism: A New Genetic Marker of Hip Fracture Risk—The Study of Osteoporotic Fractures
Authors: Cauley Jane A. , Zmuda Joseph M. , Yaffe Kristine , Kuller Lewis H. , Ferrell Robert E. , Wisniewski Stephen R. , Cummings Steven R.
Published: July 2022

Hip fractures are common and devastating events. The apolipoprotein E*4 (APOE) allele, associated with Alzheimer's disease, has also been associated with osteoporosis in hemodialysis patients. We prospectively studied 1750 women, age ≥65 years, who underwent measurements of hip and calcaneal bone mineral density (BMD), were typed for APOE and followed for ~7.0 years for the occurrence of fractures and falls. Women with at least one APOE*4 allele had an increased risk of hip fracture, relative hazard (RH) (95% confidence interval) = 1.90 (1.05–3.41) and wrist fracture, RH = 1.67 (1.01–2.77) compared with women without APOE*4, even after adjusting for age, cognitive function, falling, and BMD. The effect of APOE*4 on hip fracture was greatest among women with additional (≥3) other risk factors. Women with an APOE*4 allele were also likely to report a maternal history of fracture. The average number of falls per year did not differ by APOE*4: 0.46 for APOE*4 women and 0.41 for women without an APOE*4 allele. Women with an APOE*4 allele experienced greater weight loss which contributed to faster rates of bone loss. We conclude that women with the APOE*4 polymorphism are at substantially increased risk of hip and wrist fracture that is not explained by bone density, impaired cognitive function, or falling. Passible alternate explanations include an effect of APOE on vitamin K, bone turnover, or weight loss. The APOE polymorphism may be a candidate gene for hip fractures among community dwelling nondemented women.
RaDonda Vaught, medication safety, and the profession of pharmacy: Steps to improve safety and ensure justice
Authors: Lambert Bruce L. , Schiff Gordon D.
Published: July 2022

The prosecution and ultimate conviction of nurse RaDonda Vaught is both a warning and a call to action for pharmacists and the profession of pharmacy. This essay outlines nine steps that should be taken to maximize patient safety and minimize the risk of criminal prosecution for harm that results from human error. These include advocating for safe practices that reduce the risk of wrong drug errors; using pharmacy professional organizations to educate prosecutors about just culture and system safety; strengthening the focus on at‐risk behaviors and the normalization of deviance; training a cohort of clinicians to serve as expert witnesses for the defense; embracing communication and resolution programs as responses to unexpected harm; encouraging and supporting conservative medication use to minimize exposure to medication risks; drawing attention to production pressures and their impact on patient safety and clinician burnout; promoting proactive surveillance for adverse drug effects; and standing in solidarity with other health professions, especially nursing.
Pre‐clinical evaluation of fretting‐corrosion at stem‐head and stem‐cement interfaces of hip implants using in vitro and in silico models
Authors: dos Santos Vinícius Oliveira , Cubillos Patricia Ortega , dos Santos Claudio Teodoro , Fernandes Wellington Gilbert , de Jesus Monteiro Maurício , Caminha Ieda Maria Vieira , Moré Ari Digiácomo Ocampo , de Mello Roesler Carlos Rodrigo
Published: July 2022

Prior to clinical use, the corrosion resistance of new prosthesis system must be verified. The fretting‐corrosion mechanisms of total hip arthroplasty (THA) implants generate metal debris and ions that can increase the incidence of adverse tissue reactions. For cemented stems, there are at least two interfaces that can be damaged by fretting‐corrosion: stem‐head and stem‐cement. This investigation aimed to evaluate, through in vitro and in silico analyses, fretting‐corrosion at the stem‐head and stem‐cement interfaces, to determine which surface is most affected in pre‐clinical testing and identify the causes associated with the observed behavior. Unimodular stems and femoral heads of three different groups were evaluated, defined according to the head/stem material as group I (SS/SS), group II (CoCr/SS), and group III (CoCr/CoCr). Seven pairs of stems and heads per group were tested: three pairs were subjected to material characterization, three pairs to in vitro fretting‐corrosion testing, and one pair to geometric modeling in the in silico analysis. The absolute area of the stem body degraded was more than three times higher compared with the trunnion, for all groups. These results were corroborated by the in silico analysis results, which revealed that the average micromotion at the stem‐cement interface (9.65–15.66 μm) was higher than that at the stem‐head interface (0.55–1.08 μm). In conclusion, the degradation of the stem‐cement interface is predominant in the pre‐clinical set, indicating the need to consider the fretting‐corrosion at the stem‐cement interface during pre‐clinical implant evaluations.
A preliminary evaluation of in vivo response to a filament‐wound macroporous collagen midurethral sling in an ovine model
Authors: Khalifa Ahmad O. , Isali Ilaha , Celik Hakan , Mastran Michael , McClellan Phillip , Gillespie Callan , Shankar Subba , MacLennan Gregory T. , Anderson James M. , Schumacher Fredrick R. , Akkus Ozan , Hijaz Adonis K.
Published: July 2022

Stress urinary incontinence (SUI) impacts ~1/3 of women over age 50. Negative publicity around PP meshes used in pelvic prolapse repair drives the need for identifying alternative biomaterials for SUI repair. Our study evaluated in vivo response to collagen sling implanted in an ovine model. Electrocompacted collagen threads were filament wound as slings and crosslinked in genipin. Collagen slings were implanted suburethrally mimicking the transvaginal tape technique. Main study groups were: Collagen sling (n = 3, 6 months) and PP sling (n = 3, 6 months). Collagen sling was also tested at 3‐weeks (n = 1) to observe early‐stage tissue response and 1‐year (n = 2) to assess biomaterial longevity in a preliminary capacity. Collagen slings healed to a fibrous ligament texture at 6 months and maintained such texture to 1 year. Histological scoring indicated biocompatible responses to collagen slings with no adverse events. All study groups exhibited complete tissue ingrowth and interstitial de novo collagen deposition at all time points. Collagen threads induced orderly de novo collagen deposition that was aligned along long axes of threads. Tissue infiltrated collagen slings that were explanted at 6 and 12 months presented similar structural strength with native tissues such as vagina and fascia, and PP (Lynx) slings (p > .05). With the limitation of low number of animals per time point in hindsight, this preliminary study justifies evaluation of collagen slings in a larger sample size of animals, particularly to assess persistence of ligamentous tissue response over longer durations than 1‐year.
A dilute‐and‐shoot liquid chromatography–tandem mass spectrometry method for urinary 18‐hydroxycortisol quantification and its application in establishing reference intervals
Authors: Zhao Beibei , Bian Jin , Rao Menghua , She Xuhui , Lou Ying , Cai Jun , Ma Wenjun
Published: July 2022

Background

Eighteen‐hydroxycortisol (18‐OHF) is a potential biomarker for differential diagnosis of the two major primary aldosteronism subtypes, aldosterone‐producing adenoma, and idiopathic hyperaldosteronism.

Methods

Urine samples were processed, and the 18‐OHF in urine samples were successfully quantified by in‐house established dilute‐and‐shoot liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. Separation was accomplished on a Sigma Ascentis Express C18 column with a gradient mixture of phase (A) 0.2% formic acid in water and phase (B) 0.2% formic acid in methanol at a flow rate of 0.4 ml/min. Mass spectrometric detection was performed in positive electrospray ionization mode via a mass spectrometer.

Results

The linearity of urinary 18‐OHF ranged from 4.28 to 8.77 × 103 nmol/L, with a lower limit of quantification at 4.28 nmol/L. The intra‐ and inter‐precision were both below 3%. The range of analytical recovery was 97.8%–109.2%. The validated dilute‐and‐shoot LC–MS/MS method was compared with the SPE LC–MS/MS method modified from the one reported in 2013. The results by Passing–Bablok regression analysis and Bland–Altman plotting demonstrated a good agreement between the two methods. The presented method was then applied to establish sex‐specific reference intervals from 62 males and 62 females, respectively. The calculated 2.5%–97.5% reference intervals for 24‐h urinary 18‐OHF were 113–703 nmol/day for males and 71.2–450 nmol/day for females.

Conclusion

The presented dilute‐and‐shoot LC–MS/MS method for 18‐OHF quantification showed a good performance in the clinical application. Furthermore, the sex‐specific reference intervals for 24‐h urinary 18‐OHF were first established and quite important for its application in primary aldosteronism subtyping.
hsa_circ_0115355 promotes pancreatic β‐cell function in patients with type 2 diabetes through the miR‐145/SIRT1 axis
Authors: Dai Ying , Ma Xudan , Zhang Jiangnan , Yu Shuting , Zhu Yuchao , Wang Jianhua
Published: July 2022

Background

Type 2 diabetes mellitus (T2DM) is a complex metabolic disease closely related to obesity, a growing global health problem. T2DM is characterized by decreased islet beta‐cell mass and impaired insulin release from these cells, and this dysfunction is exacerbated by hyperglycemia (glucolipotoxicity). Circular RNAs (circRNAs) are abnormally expressed and play a regulatory role in T2DM.

Objective

This study aimed to evaluate the function and molecular mechanism of hsa_circ_0115355 in the progression of T2DM.

Methods

The regulatory effect of hsa_circ_0115355 on INS‐1 cell function was assessed under glucolipotoxicity by MTT, flow cytometry analysis, and insulin secretion assay. Dual‐luciferase experiments revealed a direct interaction of hsa_circ_0115355 with miR‐145 and miR‐145 with SIRT1. Furthermore, the regulatory role of the hsa_circ_0115355/miR‐145/SIRT1 axis was verified by examining the function of INS‐1.

Results

In this study, hsa_circ_0115355 was significantly underexpressed in both patients with T2DM and INS‐1 cell lines. This study thus showed that hsa_circ_0115355 inhibits the occurrence and development of T2DM by regulating the expression of SIRT1 by adsorbing miR‐145.

Conclusion

The underexpression hsa_circ_0115355 is also a potential novel diagnostic marker and therapeutic target for T2DM.
Proteomic analysis of MSC‐derived apoptotic vesicles identifies Fas inheritance to ameliorate haemophilia a via activating platelet functions
Authors: Zhang Xiao , Tang Jianxia , Kou Xiaoxing , Huang Weiying , Zhu Yuan , Jiang Yuhe , Yang Kunkun , Li Can , Hao Meng , Qu Yan , Ma Lan , Chen Chider , Shi Songtao , Zhou Yongsheng
Published: July 2022

Apoptotic vesicles (apoVs) are apoptotic cell‐derived nanosized vesicles that play a crucial role in multiple pathophysiological settings. However, their detailed characteristics, specific surface markers, and biological properties are not fully elucidated. In this study, we compared mesenchymal stem cell (MSC)‐derived apoVs and exosomes from three different types of MSCs including human bone marrow MSCs (hBMSCs), human adipose MSCs (hASCs), and mouse bone marrow MSCs (mBMSCs). We established a unique protein map of MSC‐derived apoVs and identified the differences between apoVs and exosomes in terms of functional protein cargo and surface markers. Furthermore, we identified 13 proteins specifically enriched in apoVs compared to exosomes, which can be used as apoV‐specific biomarkers. In addition, we showed that apoVs inherited apoptotic imprints such as Fas to ameliorate haemophilia A in factor VIII knockout mice via binding to the platelets’ FasL to activate platelet functions, and therefore rescuing the blood clotting disorder. In summary, we systemically characterized MSC‐derived apoVs and identified their therapeutic role in haemophilia A treatment through a previously unknown Fas/FasL linkage mechanism.
Primary care nurses during the coronavirus disaster and their struggle: Qualitative research
Authors: Mizumoto Junki , Mitsuyama Toshichika , Kumagaya Shinichiro , Eto Masato , Izumiya Masashi , Horita Shoko
Published: July 2022

Background

Coronavirus disease 2019 (COVID‐19) has substantially affected the health and lives of medical professionals. However, the experiences of nurses engaged in primary care remain unclear. We explored how nurses working in primary care were psychologically and socially affected by the COVID‐19 disaster and how they overcame the difficulties experienced.

Methods

We conducted a qualitative study of seven Japanese nurses working in primary care. Data collection was performed before, during, and after a workshop based on the Tojisha‐Kenkyu (user‐led research) framework to explore how the COVID‐19 disaster affected the nurses and how they coped. Data were analyzed using inductive thematic analysis.

Results

Three themes emerged from the analysis: effects of the COVID‐19 disaster on nurses, nurses' newly found strength during the pandemic, and their changes and achievements through the Tojisha‐Kenkyu framework. The first theme comprised four subthemes: fear of the unknown; difficulty in adaptation; dysfunction in patient care; and defilement and oppression. The second theme involved feeling in control and professionalism. The third theme, which was based on participants' discovery of “same and different” fellowships, showed work reconstruction and self‐understanding, which alleviated their difficulties.

Conclusions

The effect of the pandemic on nurses working in primary care ranges from work‐related frustration to daily life issues. The Tojisha‐Kenkyu method can help nurses to alleviate difficulties. Further research should be conducted to elucidate the constant burden on primary care professionals and establish appropriate occupational and daily life support during pandemics.
Variants in the new E1ʹ cryptic exon of the VHL gene associated with congenital erythrocytosis—Description of three cases
Authors: Rodrigues Catarina Dantas , Pombal Rita , Pereira Janet , Relvas Luís , Cunha Elizabete , Almeida José Carlos , Maia Tabita , Silva Helena , Bento Celeste
Published: July 2022

Congenital erythrocytosis (CE) represents a rare and heterogeneous group of hereditary disorders. The molecular basis of VHL gene mutations related to CE. Recently, Lenglet et al. reported a discovery of a novel cryptic exon in the VHL gene. Mutations in the first intronic region resulting in the creation of a cryptic exon termed E1ʹ were found in seven families with CE and one family with VHL disease. We report three patients with prolonged CE with the aetiology being clarified several years later by sequencing of intronic region 1 of the VHL gene. This work addresses the first cases reported at the clinical level of VHL‐associated CE due to the E1ʹ cryptic exon.
COVID‐19's impacts on business activities and female workers: Empirical evidence from global developing economies
Authors: Wu Ruohan
Published: July 2022

This paper empirically examines the economic impacts of COVID‐19 on firms' business activities and female workers in 10 developing economies around the world. Based on a survey conducted by the World Bank, we constructed a firm‐level panel dataset and investigated how firms' production and finances have developed during COVID‐19. We also investigated female workers' employment situations and how they were affected by firm performance. COVID‐19 indeed casted seriously adverse impacts in the developing world. As time passes, firms' production has been recovering, but their finances are worsening, and the female workers are facing worse situations in forms of higher probabilities of losing jobs and getting furloughed. Other variables such as workforce, capacity utilisation, and exports also play important roles in this process.
Using Free‐Breathing MRI to Quantify Pancreatic Fat and Investigate Spatial Heterogeneity in Children
Authors: Story Jacob D. , Ghahremani Shahnaz , Kafali Sevgi Gokce , Shih Shu‐Fu , Kuwahara Kelsey J. , Calkins Kara L. , Wu Holden H.
Published: July 2022

Background

MRI acquisition for pediatric pancreatic fat quantification is limited by breath‐holds (BH). Full segmentation (FS) or small region of interest (ROI) analysis methods may not account for pancreatic fat spatial heterogeneity, which may limit accuracy.

Purpose

To improve MRI acquisition and analysis for quantifying pancreatic proton‐density fat fraction (pPDFF) in children by investigating free‐breathing (FB)‐MRI, characterizing pPDFF spatial heterogeneity, and relating pPDFF to clinical markers.

Study Type

Prospective.

Population

A total of 34 children, including healthy (N = 16, 8 female) and overweight (N = 18, 5 female) subjects.

Field Strength and Sequences

3 T; multiecho gradient‐echo three‐dimensional (3D) stack‐of‐stars FB‐MRI, multiecho gradient‐echo 3D Cartesian BH‐MRI.

Assessment

A radiologist measured FS‐ and ROI‐based pPDFF on FB‐MRI and BH‐MRI PDFF maps, with anatomical images as references. Regional pPDFF in the pancreatic head, body, and tail were measured on FB‐MRI. FS‐pPDFF, ROI‐pPDFF, and regional pPDFF were compared, and related to clinical markers, including hemoglobin A1c.

Statistical Tests

T‐test, Bland–Altman analysis, Lin's concordance correlation coefficient (CCC), one‐way analysis of variance, and Spearman's rank correlation coefficient were used. P < 0.05 was considered significant.

Results

FS‐pPDFF and ROI‐pPDFF from FB‐MRI and BH‐MRI had mean difference = 0.4%; CCC was 0.95 for FS‐pPDFF and 0.62 for ROI‐pPDFF. FS‐pPDFF was higher than ROI‐pPDFF (10.4% ± 6.4% vs. 4.2% ± 2.8%). Tail‐pPDFF (11.6% ± 8.1%) was higher than body‐pPDFF (8.9% ± 6.3%) and head‐pPDFF (8.7% ± 5.2%). Head‐pPDFF and body‐pPDFF positively correlated with hemoglobin A1c.

Data Conclusion

FB‐MRI pPDFF is comparable to BH‐MRI. Spatial heterogeneity affects pPDFF quantification. Regional measurements of pPDFF in the head and body were correlated with hemoglobin A1c, a marker of insulin sensitivity.

Evidence Level

2

Technical Efficacy

Stage 2
Design considerations for a cycloidal mass analyzer using a focal plane array detector
Authors: Horvath Kathleen L. , Piacentino Elettra L. , Serpa Rafael Bento , Aloui Tanouir , Vyas Raul , Zhilichev Yuriy , von Windheim Jesko , Sartorelli Maria Luisa , Parker Charles B. , Denton M. Bonner , Gehm Michael E. , Glass Jeffrey T. , Amsden Jason J.
Published: July 2022

With the advent of technologies such as ion array detectors and high energy permanent magnet materials, there is renewed interest in the unique focusing properties of the cycloidal mass analyzer and its ability to enable small, high‐resolution, and high‐sensitivity instruments. However, most literature dealing with the design of cycloidal mass analyzers assumes a single channel detector because at the time of those publications, compatible multichannel detectors were not available. This manuscript introduces and discusses considerations and a procedure for designing cycloidal mass analyzers coupled with focal plane ion array detectors. To arrive at a set of relevant design considerations, we first review the unique focusing properties of the cycloidal mass analyzer and then present calculations detailing how the dimensions and position of the focal plane array detector relative to the ion source determine the possible mass ranges and resolutions of a cycloidal mass analyzer. We present derivations and calculations used to determine the volume of homogeneous electric and magnetic fields needed to contain the ion trajectories and explore the relationship between electric and magnetic field homogeneity on resolving power using finite element analysis (FEA) simulations. A set of equations relating the electric field homogeneity to the geometry of the electric sector electrodes was developed by fitting homogeneity values from 78 different FEA models. Finally, a sequence of steps is suggested for designing a cycloidal mass analyzer employing an array detector.
Dispersion of synonymous codon usage patterns in hepatitis E virus genomes derived from various hosts
Authors: Wang Xin , Sun Jing , Zheng Yueyan , Xie Fuqiang
Published: July 2022

Hepatitis E virus (HEV) is an important zoonotic pathogen infecting a wide range of host species. It has a positive‐sense, single‐stranded RNA genome encoding three open reading frames (ORFs). Synonymous codon usages of viruses essentially determine their survival and adaptation to susceptible hosts. To better understand the interplay between the ever‐expanding host range and synonymous codon usages of HEV, we quantified the dispersion of synonymous codon usages of HEV genomes isolated from different hosts via Vs calculation and information entropy. HEV ORFs show species‐specific synonymous codon usage patterns. Ruminant‐derived HEV ORFs own the most synonymous codons with stable usage patterns (Vs value <0.1) which leads to the stable overall codon usage patterns (R value being close to zero). Swine‐derived HEV ORFs own more concentrated synonymous codons than those from wild boar. Compared with HEV strains isolated from other hosts, the human‐derived HEV exhibits a distinct pattern at the overall codon usage (R < 0). Generally, ORF1 contains more synonymous codons with stable usage patterns (Vs < 0.1) than those of ORFs 2 and 3. Moreover, ORF3 contains more synonymous codons with varied patterns (Vs > 1.0) than ORFs 1 and 2. The host factor serving as one of the evolutionary dynamics probably influences synonymous codon usage patterns of the HEV genome. Taken together, synonymous codons with stable usage patterns in ORF1 might help to sustain the infection, while that with varied usage patterns in ORF3 may facilitate cross‐species infection and expand the host range.
Surgery of resectable local recurrence following colorectal cancer: Compartmental surgery improves local control
Authors: Dumont Frédéric , Loaec Cécile , Wernert Romuald , Maurel Blandine , Thibaudeau Emilie , Vilcot Laurence
Published: July 2022

Background

This study aims to identify prognostic factors and define the best extent of surgery for optimizing treatment of local recurrence (LR) following colorectal cancer (CRC).

Methods

An institutional database of consecutive patients who underwent radical resection (R0/R1) of LR following CRC was analyzed prospectively from 2010 to 2021 at one tertiary cancer center.

Results

In this study, 75 patients were included with LR following CRC and analyzed. Patients were categorized as compartmental resections (CompRe) (n = 47) if all adjacent organs were systematically removed, with or without tumor involvement, or noncompartmental resections (NoCompRe) (n = 28) if only contiguously involved organs were resected. NoCompRe were mainly related to contact between major vessels or bone and the tumor, with only 8/19 (42.1%) resections.

Five‐year overall survival and locoregional‐free survival were 37.5% and 38.8% respectively. Local control was better in the CompRe than the NocompRe group (61.4% vs. 11%; p < 0.01). CompRe (hazard ratio: 2.34 [1.16–4.68]; p = 0.017) and absence of peritoneal metastasis (3.05 [1.03–9.02]; p = 0.044) were the two factors associated with decreased abdominal recurrences in multivariate analysis.

Conclusion

Complete compartmental surgery is safe and improves local control. Optimal LR resection needs to remove all contiguous organs, with or without tumor involvement.
Cesarean Scar Pregnancies Treated by Uterine Artery Chemotherapy Embolization Combined With Ultrasound‐Guided Dilation and Curettage
Authors: Zheng Yi‐Jun , Chen Qing , Li Sheng , Yan Xiao‐Tong , Zhu Ting , He Zheng
Published: July 2022

Objectives

To explore the effect of cesarean scar pregnancy (CSP) treatment by comparing uterine artery chemotherapy embolization (UACE) combined with dilation and curettage (D&C) with or without ultrasound guidance.

Methods

CSP patients treated with UACE combined with D&C from January 2013 to December 2020 at Shuguang Hospital, affiliated to Shanghai University of Traditional Chinese Medicine were included in this retrospective study. The patients were divided into groups A and B according to whether D&C was guided by ultrasound.

Results

Forty‐eight patients with CSP diagnosed by transvaginal ultrasound were included in this study, whose gestational age was <8 weeks. There were no significant differences in the basic clinical characteristics of the two groups. The success rates of the 2 groups were no significant difference, 100% (27/27) in group A and 85.7% (18/21) in group B. The maximal intraoperative blood loss of group A was 100 mL and that of group B was 150 mL. There was no uterine perforation during the operation. Ultrasound guidance can shorten the D&C operation time, reduce intraoperative bleeding during D&C, and decrease the residual rate of trophoblastic tissue after D&C.

Conclusions

Ultrasound guidance can improve the safety and efficiency of UACE combined with D&C in the treatment of CSP and reduce its complications. We believe it is an optimal treatment for CSP patients who do not plan to have children in the future.
Anaplastic Transformation of Differentiated Thyroid Carcinoma
Authors: Yu Alice C. , Han Albert Y. , Cronkite David Alex , Sajed Dipti , St. John Maie A.
Published: July 2022

Objectives

Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive form of thyroid cancer. Increasingly, patients with ATC present with concurrent foci of well‐differentiated thyroid carcinoma (WDTC); however, the significance of these pathologic findings remains unclear. The objective of this study is to determine whether the presence of WDTC within anaplastic tumors is a prognosticator of survival.

Methods

A retrospective cohort study of all cases of biopsy‐proven ATC managed at a tertiary care academic medical center from 2002 to 2020 was performed. Mean age at diagnosis, median survival time, and locations of distant metastases were assessed. The impact of clinical markers such as presence of differentiation, demographic variables, and oncologic information on overall survival was also determined via univariate and multivariate analysis.

Results

Forty‐five patients were included in this study. The mean age at diagnosis was 69.1 years. Median survival time was 6.1 months after diagnosis. The most common location of distant metastases was the lung (40%). The presence of limited areas of WDTC in patients with predominantly anaplastic thyroid tumors was not significantly associated with improved outcomes (p = 0.509). Smaller tumor size and use of chemotherapy in ATC patients were significantly associated with prolonged survival (p = 0.026 and 0.010, respectively).

Conclusions

Clinical outcomes for ATC remain poor. The presence of foci of differentiation within anaplastic thyroid tumors does not appear to improve overall survival—the anaplastic component evidently drives outcomes. Further studies into novel therapies are needed to improve survival in ATC.

Level of Evidence

4 Laryngoscope, 133:437–442, 2023
Structurally‐engineered fatty acid 1024 (SEFA‐1024) improves diet‐induced obesity, insulin resistance, and fatty liver disease
Authors: Secor Jordon D. , Cho Bennet S. , Yu Lumeng J. , Pan Amy , Ko Victoria H. , Dao Duy T. , Feigh Michael , Anez‐Bustillos Lorenzo , Fell Gillian L. , Fraser David A. , Gura Kathleen M. , Puder Mark
Published: July 2022

Obesity is a global epidemic that drives morbidity and mortality through cardiovascular disease, diabetes, and non‐alcoholic fatty liver disease (NAFLD). No definitive therapy has been approved to improve glycemic control and treat NAFLD in obese patients. Here, we investigated a semi‐synthetic, long chain, structurally‐engineered fatty acid‐1024 (SEFA‐1024), as a treatment for obesity‐induced hyperglycemia, insulin‐resistance, and fatty liver disease in rodent models. A single dose of SEFA‐1024 was administered to evaluate glucose tolerance and active glucagon‐like peptide 1 (GLP‐1) in lean rats in the presence and absence of a DPP‐4 inhibitor. The effects of SEFA‐1024 on weight loss and glycemic control were assessed in genetic (ob/ob) and environmental (high‐fat diet) murine models of obesity. Liver histology, serum liver enzymes, liver lipidomics, and hepatic gene expression were also assessed in the high‐fat diet murine model. SEFA‐1024 reversed obesity‐associated insulin resistance and improved glycemic control. SEFA‐1024 increased active GLP‐1. In a long‐term model of diet‐induced obesity, SEFA‐1024 reversed excessive weight gain, hepatic steatosis, elevated liver enzymes, hepatic lipotoxicity, and promoted fatty acid metabolism. SEFA‐1024 is an enterohepatic‐targeted, eicosapentaenoic acid derivative that reverses obesity‐induced dysregulated glucose metabolism and hepatic lipotoxicity in genetic and dietary rodent models of obesity. The mechanism by which SEFA‐1024 works may include increasing aGLP‐1, promoting fatty acid oxidation, and inhibiting hepatic triglyceride formation. SEFA‐1024 may serve as a potential treatment for obesity‐related diabetes and NAFLD.
Correlation between adipocyte fatty acid binding protein and glucose dysregulation is closely associated with obesity and metabolic syndrome: A cohort of Han Chinese population from Yunnan plateau
Authors: Huang Juan , Chen Guo , Zhang Qiao , Wang Yanjiao , Meng Qiong , Xu Fang , Zhang Xuehui , Zou Wei , Mi Fei , Yin Jianzhong
Published: July 2022

The present study investigated the correlation of plasma A‐FABP with glucose dysregulation under different body mass index (BMI) and metabolic states in a Han Chinese population from Yunnan plateau. We cross‐sectionally analyzed data from the China Multi Ethnic Cohort, Yunnan province. Participants were divided into two groups. Group A contained 297 obese individuals with metabolic syndrome (MetS). Group B contained 326 age‐, sex‐, and region‐matched normal BMI subjects without MetS. Glucose dysregulation was defined as elevated fasting plasma glucose (FPG) (FPG ≥ 5.6 mmol/L or current use of oral hypoglycemic agents or insulin). Circulating A‐FABP were assayed by ELISA method. Binary and multiple regression analyses were preformed to evaluate the correlation between A‐FABP and glucose dysregulation. Plasma A‐FABP level was significantly higher in group A compared with group B (p < 0.001). Plasma A‐FABP level correlated positively with elevated FPG in group A (r = 0.120, p = 0.039), but negatively with elevated FPG in group B (r = −0.115, p = 0.039). Multiple logistic regression analysis revealed that A‐FABP was an independent predictor for elevated FPG in group A (β, 0.028; 95% CI, 1.001–1.056; p < 0.05), but not in group B (β, −0.008; 95% CI, 0.882–1.117; p > 0.05). In this study, A‐FABP was an independent risk factor for glucose dysregulation in obese individuals with MetS living in the Yunnan plateau, but not for those without obesity and MetS.
HPLC and 32P‐radiolabeling method for quantification of microbial adenylate concentrations and turnover rates in seawater
Authors: Lanpher Kaycie B. , Popendorf Kimberly J.
Published: July 2022

We optimized a high throughput method to quantify turnover rates of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) in marine microbes from simultaneous measures of the respective stocks and phosphorylation rates. We combined a microbial adenylate extraction method using boiling 20 mM Tris buffer with purification and analysis by high pressure liquid chromatography optimized to quantify these intracellular adenylate concentrations in marine microbes. Additionally, we incorporated radiolabeled phosphate (32Pi) incubations to quantify phosphorus (P) uptake rates and the phosphorylation rates for these adenylate compounds in microbial cells. With this method, we can directly assess the variations in microbial growth rates, metabolic turnover rates, energy charge, and adenylate storage. We applied and validated this method application with environmental samples from Biscayne Bay, Florida, and quantified adenylate turnover times of 12, 15, and 73 min, for ATP, ADP, and AMP, respectively. Future incorporation of this method into experiments and geographic surveys across marine environments will allow for direct assessments of changes in microbial metabolic activity in relation to other ecological variables.
Physics‐Informed Neural Network for Nonlinear Dynamics in Fiber Optics
Authors: Jiang Xiaotian , Wang Danshi , Fan Qirui , Zhang Min , Lu Chao , Lau Alan Pak Tao
Published: July 2022

A physics‐informed neural network (PINN) that combines deep learning with physics is studied to solve the nonlinear Schrödinger equation for learning nonlinear dynamics in fiber optics. A systematic investigation and comprehensive verification on PINN for multiple physical effects in optical fibers is carried out, including dispersion, self‐phase modulation, and higher‐order nonlinear effects. Moreover, both the special case (soliton propagation) and general case (multipulse propagation) are investigated and realized with PINN. In existing studies, PINN is mainly effective for a single scenario. To overcome this problem, the physical parameters (i.e., pulse peak power and amplitudes of subpulses) are hereby embedded as additional input parameter controllers, which allow PINN to learn the physical constraints of different scenarios and perform good generalizability. Furthermore, PINN exhibits better performance than the data‐driven neural network using much less data, and its computational complexity (in terms of number of multiplications) is much lower than that of the split‐step Fourier method. The results show that PINN is not only an effective partial differential equation solver, but also a prospective technique to advance the scientific computing and automatic modeling in fiber optics.
On‐Chip High‐Speed Coherent Optical Signal Detection Based on Photonic Spin‐Hall Effect
Authors: Lei Ting , Zhou Changyu , Wang Dawei , Xie Zhenwei , Cai Boyuan , Gao Shecheng , Xie Youpeng , Du Luping , Li Zhaohui , Zayats Anatoly V. , Yuan Xiaocong
Published: July 2022

The use of coherent optical signal processing in long‐distance optical communication systems has dramatically increased data capacity enabling encoding of multiple‐bit information in the phase of a light beam. Direct detection of phase information of a high‐speed modulated light remains challenging and requires an external, local oscillator for referencing, which is expensive for short‐reach optical communications, for example, in data centers. The availability of less‐complex integrated photonics devices for coherent signal detection will alleviate this bottleneck. On the other hand, phase information of coherent, orthogonally polarized light beams can be extracted from their polarization states, and it is, therefore, possible to achieve phase measurements via fast polarization detection. Here, an on‐chip nanodisk device is demonstrated for high‐speed coherent optical signal detection enabled by spin–orbit coupling in Si‐photonics circuitry. In a coherent communication experiment with up to 32 GBaud rate, the high‐speed phase‐shift keying and quadrature amplitude modulation signals detected by a Si nanodisk based polarization measurements at multiple wavelengths in theC‐band are recovered with a bit error rate below the forward error correction threshold. The proposed on‐chip nanodisk device shows promise in high‐speed coherent optical communication applications where phase detection is required at low cost and small footprint.
Single‐Shot Recognition of 3D Phase Images With Deep Learning
Authors: Fan Weiru , Chen Tianrun , Xu Xingqi , Chen Ziyang , Hu Huizhu , Zhang Delong , Wang Da‐Wei , Pu Jixiong , Zhu Shi‐Yao
Published: July 2022

Optical phase is a key information carrier in biomedical imaging and astronomical observation. However, it is often obscured by heterogeneous and scattering media, rendering optical phase imaging an utmost challenge. Limited by the memory effect or confinement, current methods have difficulties in retrieving phases at different depths. To address this challenge, a speckle three‐dimensional reconstruction network (STRN) is developed to solve the inverse problem of the scattering process. STRN is featured by stacked convolutional filters to distinguish the depth of each image from the spatially overlapped speckles. From single‐shot, reference‐free, and scanning‐free speckle patterns, STRN simultaneously extracts multiple phase objects at different depths with high fidelity. This new approach breaks the limitations of conventional approaches for phase reconstruction through scattering media and paves a novel avenue for optical communication and biological endoscopy applications.
Coaxial Micro Ring Arrays Fabricated on Self‐Assembled Microtube Cavities for Resonant Light Modulation
Authors: Saggau Christian N. , Valligatla Sreeramulu , Wang Xiaoyu , Dong Haiyun , Ma Libo , Schmidt Oliver G.
Published: July 2022

Composite optical microcavities, as a versatile platform for light manipulation, have been theoretically revealed that the configuration of concentrically coupled resonant trajectories can significantly enhance the coupling strength, which is however challenging in experimental preparation. Here coaxial whispering gallery resonator chains were designed and fabricated with optically coupled modes split apart by more than the free spectral range (FSR) of the cavity itself. Because such three dimensional (3D) coupled optical systems are extremely difficult to obtain with traditional processing techniques an approach is developed to release and roll‐up pre‐strained, nanostructured silicon nitride membranes into microtubular optical cavities. Parallel nano‐ridges modified on the patterned membranes form into coaxial micro ring arrays after the membrane rolls up into a microtubular structure. Energetic degeneracy, as a consequence of mode splitting exceeding the FSR, leads to interference between bonding and antibonding modes with different mode identities (mode number), resulting in novel light modulation in the form of hybrid super wave modes, which display a distinct hopping behavior resembling linear stretch modes of an oscillator chain.