bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer Risk in Patients With Biopsy‐Confirmed Nonalcoholic Fatty Liver Disease: A Population‐Based Cohort Study
Authors: Simon Tracey G. , Roelstraete Bjorn , Sharma Rajani , Khalili Hamed , Hagström Hannes , Ludvigsson Jonas F.
Published: April 2021

Background and Aims

Recent studies link NAFLD to an increased incidence of HCC and extrahepatic cancers. However, earlier studies were small or lacked liver histology, which remains the gold standard for staging NAFLD severity.

Approach and Results

We conducted a population‐based cohort study of all adults with histologically defined NAFLD in Sweden from 1966 to 2016 (N = 8,892). NAFLD was defined from prospectively recorded liver histopathology submitted to all 28 Swedish pathology departments and categorized as simple steatosis, nonfibrotic NASH, noncirrhotic fibrosis, and cirrhosis. NAFLD patients were individually matched to ≤5 general population controls without NAFLD by age, sex, calendar year, and county (N = 39,907). Using Cox proportional hazards modeling, we calculated multivariable adjusted HRs (aHRs) and 95% CIs. Over a median of 13.8 years, we documented 1,691 incident cancers among NAFLD patients and 6,733 among controls. Compared with controls, NAFLD patients had significantly increased overall cancer incidence (10.9 vs. 13.8 per 1,000 person‐years [PYs]; difference = 2.9 per 1,000 PYs; aHR, 1.27 [95% CI, 1.18‐1.36]), driven primarily by HCC (difference = 1.1 per 1,000 PYs; aHR, 17.08 [95% CI, 11.56‐25.25]). HCC incidence rates increased monotonically across categories of simple steatosis, nonfibrotic NASH, noncirrhotic fibrosis, and cirrhosis (0.8 per 1,000 PYs, 1.2 per 1,000 PYs, 2.3 per 1,000 PYs, and 6.2 per 1,000 PYs, respectively; P
trend < 0.01) and were further amplified by diabetes (1.2 per 1,000 PYs, 2.9 per 1,000 PYs, 7.2 per 1,000 PYs, and 15.7 per 1,000 PYs, respectively). In contrast, NAFLD was associated with modestly increased rates of pancreatic cancer, kidney/bladder cancer, and melanoma (differences = 0.2 per 1,000 PYs, 0.1 per 1,000 PYs, and 0.2 per 1,000 PYs, respectively), but no other cancers.

Conclusions

Compared with controls, patients with biopsy‐proven NAFLD had significantly increased cancer incidence, attributable primarily to HCC, whereas the contribution of extrahepatic cancers was modest. Although HCC risk was highest with cirrhosis, substantial excess risk was also found with noncirrhotic fibrosis and comorbid diabetes.
Reliability of recharge rates estimated from groundwater age with a simplified analytical approach
Authors: Dong Yanhui , Xie Yueqing , Zhang Jun , Love Andrew J. , Dai Xin
Published: April 2021

Groundwater age is often used to estimate groundwater recharge through a simplified analytical approach. This estimated recharge is thought to be representative of the mean recharge between the point of entry and the sampling point. However, given the complexity in actual recharge, whether the mean recharge is reasonable is still unclear. This study examined the validity of the method to estimate long‐term average groundwater recharge and the possibility of obtaining reasonable spatial recharge pattern. We first validated our model in producing reasonable age distributions using a constant flux boundary condition. We then generated different flow fields and age patterns by using various spatially varying flux boundary conditions with different magnitudes and wavelengths. Groundwater recharge was estimated and analysed afterwards using the method at the spatial scale. We illustrated the main findings with a field example in the end. Our results suggest that we can estimate long‐term average groundwater recharge with 10% error in many parts of an aquifer. The size of these areas decreases with the increase in both the amplitude and the wavelength. The chance of obtaining a reasonable groundwater recharge is higher if an age sample is collected from the middle of an aquifer and at downstream areas. Our study also indicates that the method can also be used to estimate local groundwater recharge if age samples are collected close to the water table. However, care must be taken to determine groundwater age regardless of conditions.
Obstetric fistula scoring tool for surgical trainees
Authors: Pope Rachel , Mernoff Rachel , Chalamanda Chisomo , Bengtson Angela M.
Published: April 2021

Objective

To examine the ability of a previously published risk score to predict incontinence at discharge in women with vesicovaginal fistulas (VVF) and to examine how the score correlates with an independent assessment of surgical skill.

Methods

This is a retrospective cohort study including cases from January to June 2018. We evaluated operative records for factors associated with incontinence at hospital discharge, as well as relationships between a risk score cut‐point of 20 or more and surgical skill level. All women with VVF undergoing vaginal repair were included.

Results

A total of 176 individuals underwent repair; 23 were performed by beginner, 85 by intermediate, 47 by advanced, and 21 by expert surgeons. Factors found significantly associated with incontinence at hospital discharge included Goh classification, fistula size, circumferential fistula, and vaginal scarring. A score of 20 or more predicted residual incontinence with a negative predictive value of 92% (odds ratio 7.75, 95% confidence interval 2.95–22.34). Applying the score cut‐point of 20 or more, we found an increased proportion of “high‐risk” cases allocated to surgeons with an increasing level of expertise.

Conclusion

The correlation we observed between a risk score cut‐point of 20 or more, continence status, and an independent assessment of surgical skill is promising. Although the risk score is not meant to replace clinical judgment, it may provide a surgical trainee with an objective method of determining whether to operate or refer for optimal outcomes.
Outcomes of donor versus partner sperm in intrauterine insemination in women aged 38 years and older
Authors: Frank Russell , Steiner Naama , Al Shatti Maryam , Ruiter‐Ligeti Jacob , Dahan Michael H.
Published: April 2021

Objective

To compare pregnancy rates of donor versus partner sperm in intrauterine insemination (IUI) cycles in women aged 38 years and above.

Methods

A retrospective cohort study was performed using data from 944 women aged 38–43 years old who underwent a combined 1596 IUI cycles at an academic fertility clinic in Montreal, Canada between February 2009 to April 2018.

Results

Partner sperm was used in 1421 cycles (89.0%), and donor sperm was inseminated in 175 cycles (11.0%). Mean ages of the women were 39.8 (±1.5) and 40.2 (±1.6) years in the partner and donor insemination groups, respectively (P < 0.001). Positive serum (β human chorionic gonadotropin) pregnancy rate in the partner sperm group was 9.0% (n = 128) whereas that in the donor insemination group was 9.7% (n = 17) (P = 0.759). Clinical pregnancy rates were 5.8% (n = 83) and 8.0% (n = 14) in the respective groups (P = 0.260). There were five multiple gestation (twin) pregnancies in the cohort, three in those undergoing IUI with partner sperm and two in those undergoing IUI with donor sperm.

Conclusion

In women aged 38–43 years undergoing IUI with controlled ovarian stimulation, using donor sperm, compared with partner sperm, did not increase rate of pregnancy.
The developmental cascade of early parenting, emergence of executive functioning, and emotional symptoms across childhood
Authors: Murphy Yolanda E. , Zhang Xutong , Gatzke‐Kopp Lisa
Published: April 2021

Many studies focus on proximal associations between parental sensitivity and emotional well‐being in early childhood, with less data examining how parenting in infancy predicts children's emotional trajectories across childhood, in particular negative emotional symptoms of anxiety and depression. Thus, this study utilized data from The Family Life Project (N = 1015), a prospective study of child development in rural poverty, and assessed whether sensitive parenting in the first 4 years of life predicted child internalizing emotional symptoms (i.e., anxiety and depression) from kindergarten to fifth grade and whether early child executive functioning mediated this relationship. Path models indicated that observation of sensitive parenting predicted a decrease in teachers’ report of child negative emotional symptoms over time and predicted fewer negative emotional symptoms in fifth grade. Moreover, though executive functioning performance did not mediate change in symptoms over time, executive functioning did mediate the relationship between sensitive parenting and fifth‐grade symptoms, suggesting that executive functioning is one mechanism by which early sensitive parenting buffers long‐term emotional development. Findings highlight the importance of early parenting and executive functioning in development of anxiety and depression symptoms and suggests potential targets for transdiagnostic intervention.
The Lived Experiences of Addiction Counselors After Marijuana Legalization
Authors: Sperandio Katharine R. , Gutierrez Daniel , Hilert Alex , Fan Shuhui
Published: April 2021

This qualitative study examines the perceptions of counselors who work with populations with addictions in states where marijuana has been legalized. Findings include themes related to client experiences, counselor experiences, specific interventions, and lack of understanding.
Preparation and biological characteristics of a bovine acellular tendon fiber material
Authors: Zhou Shengyuan , Yuan Bo , Huang Wenmao , Tang Yifan , Chen Xiongsheng
Published: April 2021

Acellular tendon matrix is an ideal substitute for constructing tissue engineering ligaments, but using detergents causes damage to collagen and fibrin during the process of decellularization. In this study, fresh tendons were lyophilized and separated into fresh tendon fiber (FTF) bundles, and then the cellular components in FTF were removed to prepare acellular tendon fiber (ATF) without adding chemical detergent. H&E staining and DAPI fluorescence microscopy showed no nucleus and DNA residue. Compared with FTFs, the DNA content of ATFs was significantly lower without the collagen content change before and after decellularization. The microstructure of collagen fibrils in ATFs was intact under scanning electron microscopy (SEM), and the maximum tensile load and elastic modulus between FTFs and ATFs were not statistically different. The ATF bundles were cultured with SD rat tenocytes for 72 hr and cells attachment to fiber surfaces were observed under SEM. ATF bundles were then implanted into paraspinal muscles, and histological analysis showed fibroblast‐like cells within the ATFs and was similar to the control group (fresh tendon autograft) in morphology. H&E staining showed that the number of lymphocytes and plasma cells in ATF was less than that in fresh tendon autograft. ATF bundles were twisted into linear fiber materials by hand, of which the maximum breaking strength was similar to silk with same diameter. These findings demonstrated that ATFs retain their original fibril structure and mechanical properties after decellularization by trypsin and pancreatic deoxyribonuclease without detergent. Lyophilized ATFs linear fiber material provides the possibility of preparing personalized ligament and other tissue engineering scaffolds.
Formulation and characterization of hydroxyapatite‐based composite with enhanced compressive strength and controlled antibiotic release
Authors: Ait Said Hamid , Noukrati Hassan , Oudadesse Hassane , Ben Youcef Hicham , Lefeuvre Bertrand , Hakkou Rachid , Lahcini Mohammed , Barroug Allal
Published: April 2021

A composite based on hydroxyapatite (HA) and chitosan (CS) combined with ciprofloxacin (CIP) was formulated by the solid–liquid mixing method. The optimization of the solid to the liquid ratio and the use of chitosan in a small amount (≤5 wt%) promoted the preparation of stable and rigid monoliths. A synergistic effect of CS and CIP contents on the compressive strength of the CIP‐loaded composite was evidenced. The compressive strength of the fabricated biocomposite ranged in values from 1 to 6 MPa, comparable to those reported for cancellous bone. The improvement of the mechanical properties with the increase of the rate of organic components was correlated with the diminution of the surface area and the reduction in the pore volume of the specimens. On the other hand, the in vitro release experiments of the antibiotic indicated a sustained and controlled release of CIP over 10 days. Moreover, in vitro antibacterial tests performed on the biocomposite HA‐CS5‐CIP showed significant inhibition of Staphylococcus aureus and Escherichia coli pathogens. According to the showed results, the formulated composite with three‐phase components could be a promising material for bone repair and local antibiotic release for the treatment of bone infections.
Albumin covering maintains endothelial function upon magnetic iron oxide nanoparticles intravenous injection in rats
Authors: Toropova Yana G. , Zelinskaya Irina A. , Gorshkova Mariya N. , Motorina Daria S. , Korolev Dmitriy V. , Velikonivtsev Fedor S. , Gareev Kamil G.
Published: April 2021

Magnetic iron oxide nanoparticles (IONP) present the promising instrument for broad‐spectrum of clinical applications, for example, targeted drug delivery. Reactivity of nanoparticles depends on their surface area and material. In the blood plasma IONP are getting covered with an albumin crown, so it was decided to test this shell for biocompatibility. Male Wistar rats were anesthetized and underwent laparotomy. Abdominal aorta was connected to external hemodynamic loop with regulated blood flow. Hind body quarter got step‐like blood flow changing from 30 to 150 mmHg and back. This was followed with i.v. injection of IONP, albumin solution or albumin‐covered IONP and consequent similar flow changes. Central hemodynamics—heart rate and mean arterial pressure were registered throughout the experiment and no significant changes in these parameters were observed. Hind paw microcirculation level had the same dynamic in all groups under changing blood flow conditions. At the end, venous blood was collected for endothelin‐1 and NO evaluation that showed similar changes and no endothelial damage. Mesenteric arteries and femoral artery reactivity were evaluated with wire myography. Mesenteric arteries had the most relaxing function preservation after albumin‐covered IONP injection. Given data reveal advantage of albumin‐coated IONP so this can be used for further investigations as a vascular‐safe vehicle.
Solar light active flexible activated carbon cloth‐based photocatalyst for Markovnikov‐selective radical‐radical cross‐coupling of S‐nucleophiles to terminal alkyne and liquefied petroleum gas sensing
Authors: Singh Pooja , Yadav Rajesh K. , Kim Tae Wu , Yadav Tara C. , Gole Vitthal , Gupta Abhishek K. , Singh Kuldeep , Kumar Kuldeep , Yadav Bal Chandra , Dwivedi D. K.
Published: April 2021

Selective radical‐radical coupling of terminal alkynes and thiol has been broadly used in chemical synthesis, providing plausible entries to the formation of anti‐Markovnikov products. Because of the selective control and Kharasch effect, the formation of Markovnikov products still remains an immense challenge. Herein, we designed a covalent organic polymer, poly(naphthalene 1,4,5,8‐tetracarboxylic dianhydrideimide‐benzoquinone) through in situ polymerization on activated flexible carbon cloth to function as a light harvester material for selective Markovnikov radical‐radical coupling of terminal alkynes and thiol. Mechanistic explorations verified that cross‐coupling between radical of terminal alkynes and thiol might be the key route in this organic transformation, such as C—S bond formation. This selective radical‐radical Markovnikov of cross‐coupling protocol provide an opportunity to assist the synthesis of valuable vinyl sulfide. Additionally, the synthesized material has been explored as liquefied petroleum gas (LPG) sensor for 0.5, 1.0, 1.5, and 2.0 vol% LPG, respectively. At 2.0 vol% LPG, it shows maximum sensor response as 635.29. Least response and recovery times are 2.44 and 1.0 s, respectively.
Prognosis of primary sclerosing cholangitis according to age of onset
Authors: Watanabe Takeo , Nakai Yousuke , Mizuno Suguru , Hamada Tsuyoshi , Kogure Hirofumi , Hirano Kenji , Akamatsu Nobuhisa , Hasegawa Kiyoshi , Isayama Hiroyuki , Koike Kazuhiko
Published: April 2021

Background

Liver failure and biliary tract cancer (BTC) are major life‐threatening events in the clinical course of primary sclerosing cholangitis (PSC). Although these are competing events, they are typically evaluated as a composite prognostic endpoint. In Japan, the clinical characteristics and prognosis of PSC reportedly differ according to age of onset. We compared the prognosis of younger‐ versus older‐onset PSC by competing risk analysis.

Methods

This was a retrospective analysis of 144 patients with PSC who were followed up for a median of 6.7 years. The patients were divided into two groups according to a cutoff age of onset of 44 years. We compared the prognosis of younger‐onset PSC (n = 91) and older‐onset PSC (n = 53) by competing risk analysis, incorporating mortality related and that unrelated to BTC as competing events.

Results

There was no difference in BTC‐related mortality between patients with younger‐onset and those with older‐onset PSC (subdistribution hazard ratio [SHR], 0.89; 95% confidence interval [CI], 0.17‐4.56, P = .888). The cumulative incidence of mortality due to other causes, including liver transplantation and liver failure, was non‐significantly higher in patients with older‐onset PSC (SHR, 1.58; 95% CI, 0.88‐2.84; P = .129).

Conclusions

Although we did not find a significant difference in prognosis by onset age, patients with older‐onset PSC had worse liver‐transplantation‐free survival than those with younger‐onset PSC. A large cohort study is needed to evaluate the clinical outcomes of older‐ and younger‐onset PSC.
Design, synthesis, and insecticidal activities of novel diamide derivatives with alpha‐amino acid subunits
Authors: Chen Rui‐Jia , Wang Jun‐Jie , Han Li , Gu Yu‐Cheng , Xu Zhi‐Ping , Cheng Jia‐Gao , Shao Xu‐Sheng , Xu Xiao‐Yong , Li Zhong
Published: April 2021

A series of diamide derivatives containing α‐amino acids were designed and synthesized. These compounds were evaluated for their insecticidal activities against Plutella xylostella, Mythimna separate, Myzus persicae, and Tetranychus cinnabarinus. Most of the title compounds containing an l‐phenylglycine skeleton were endowed with good activities at the concentration of 500 mg·L−1. Compounds (R)‐A6 showed a potential value for further optimization as an insecticidal lead with the LC50 value of 86.8 mg·L−1.
Development and optimization of a quantitative analysis of main odorants causing off flavours in cork stoppers using headspace solid‐phase microextraction gas chromatography tandem mass spectrometry
Authors: Jové Patricia , Pareras Anna , De Nadal Raquel , Verdum Maria
Published: April 2021

A simple and sensitive method was developed and validated to simultaneously separate and determine the 2‐Methoxy‐3,5‐dimethylpyrazine, 2‐Isopropyl‐3‐methoxypyrazine, guaiacol, 2‐Isobutyl‐3‐methoxypyrazine, 2‐Methylisoborneol, geosmin, 2,4,6‐Trichloroanisole, 2,3,4,6‐Tetrachloroanisole, 2,4,6‐Tribromoanisole and Pentachloroanisole in cork stoppers via headspace solid‐phase microextraction (HS‐SPME) coupled with gas chromatography tandem mass spectrometry (GC–MS/MS). The influence of the fibre coating used, the extraction times and temperatures, the sodium chloride additions and the desorption temperatures were investigated. Once done, the optimial HS‐SPME conditions established were divinylbenzene/carboxenpolydimethylsiloxane/polydimethylsiloxane (DVB/CAR/PDMS) fibres, a 50°C extraction temperature, 60‐min extraction time, an ionic strength of 3‐g sodium chlorid and a 290°C desorption temperature. The method showed a good linearity (R2 ≥ 0.994) within the tested range (from 0.1 to 50 ng L−1) for all the compounds. Using TCA‐d10 and MIB‐d3 as internal standards the precision, expressed as repeatability and reproducibility RSD, was <10% in both. Note that the limits of quantifications (LOQs) are below the sensory threshold levels for such compounds in water and wine. Good recoveries were obtained for cork macerates (from 100.4% to 126%) and when compared with other reported methods using HS‐SPME in water and cork stopper samples, the present method had more analytes with the lowest limit of detection for most of the targeted compounds, along with good precision and recovery.
Downregulation of type III interferons in patients with severe COVID‐19
Authors: Fukuda Yosuke , Homma Tetsuya , Inoue Hideki , Onitsuka Chisato , Ikeda Hitoshi , Goto Yuiko , Sato Yoko , Kimura Tomoyuki , Hirai Kuniaki , Ohta Shin , Yamamoto Mayumi , Kusumoto Sojiro , Suzuki Shintaro , Tanaka Akihiko , Sagara Hironori
Published: April 2021

Coronavirus disease 2019 (COVID‐19) is globally rampant, and to curb the growing burden of this disease, in‐depth knowledge about its pathophysiology is needed. This was an observational study conducted at a single center to investigate serum cytokine and chemokine levels of COVID‐19 patients, based on disease severity. We included 72 consecutive COVID‐19 patients admitted to our hospital from March 21 to August 31, 2020. Patients were divided into Mild‐Moderate I (mild) and Moderate II‐Severe (severe) groups based on the COVID‐19 severity classification developed by the Ministry of Health, Labor and Welfare (MHLW) of Japan. We compared the patient characteristics as well as the serum cytokine and chemokine levels on the day of admission between the two groups. Our findings indicated that the severe group had significantly higher levels of serum fibrinogen, d‐dimer, lactate dehydrogenase, C‐reactive protein, ferritin, Krebs von den Lungen‐6, surfactant protein (SP)‐D, and SP‐A than the mild group. Strikingly, the levels of interleukin (IL)‐28A/interferon (IFN)‐λ2 were significantly lower in the severe group than in the mild group. We believe that reduced levels of type III interferons (IFN‐λs) and alterations in the levels of other cytokines and chemokines may impact the severity of the disease.
Body composition measured by bioelectrical impedance analysis is a viable alternative to magnetic resonance imaging in children with nonalcoholic fatty liver disease
Authors: Orkin Sarah , Yodoshi Toshifumi , Romantic Emily , Hitchcock Kathryn , Arce‐Clachar Ana Catalina , Bramlage Kristin , Sun Qin , Fei Lin , Xanthakos Stavra A. , Trout Andrew T. , Mouzaki Marialena
Published: April 2021

Objective

To determine the relationship between bioelectrical impedance analysis (BIA) and magnetic resonance imaging (MRI) obtained measures of body composition in children with nonalcoholic fatty liver disease (NAFLD).

Methods

Youth with obesity and NAFLD who had BIA and abdominal MRI testing were included. BIA measured skeletal muscle mass (SMM), appendicular lean mass (ALM), trunk muscle mass (TMM), and percent body fat. MRI measured total psoas muscle surface area (tPMSA) and fat compartments. Univariate analysis described the relationship between BIA‐ and MRI‐derived measurements. Multivariable regression analyses built a model with body composition measured via MRI.

Results

115 patients (82 (71%) male, 38 (33%) Hispanic, median age14 years) were included. There was a strong correlation between tPMSA and SMM, ALM, and TMM (correlation coefficients [CCs]: 0.701, 0.689, 0.708, respectively; all P < .001). Higher SMM, ALM, and TMM were associated with higher tPMSA. This association remained after controlling for age, sex, ethnicity, type 2 diabetes mellitus status, and body mass index z‐score. Total fat mass by BIA and MRI‐determined total, subcutaneous, and intraperitoneal fat area correlated significantly (CCs: 0.813, 0.808, 0.515, respectively; all P < .001). In univariate regression, higher total fat mass by BIA was associated with increased total fat area and increased fat in each of the four regions measured by MRI. After controlling for confounders, the association between total fat mass by BIA and total fat area by MRI persisted.

Conclusions

BIA measures of muscle and fat mass correlate strongly with MRI measures of tPMSA and fat areas in children with obesity and NAFLD.
The coupling coordination of relationships between tourism destination image and product country image
Authors: Zheng Peng , Li Jinkai , Wang Jiejie , Cheng Hui , Wang Qianwen
Published: April 2021

Based on coupling theory, this paper analyzes mainland Chinese tourists who had purchased Taiwanese products before they traveled to Taiwan, and presents three key findings: (1) The evaluation value of mainland Chinese tourists for tourism destination image (TDI) is higher than that of product country image (PCI). (2) The degrees of coupling coordination between TDI and PCI as well as cognitive TDI and cognitive PCI are barely balanced; the degree of coupling coordination between affective TDI and affective PCI is slightly unbalanced. (3) There are stable and fluctuating coupling coordination relationships between TDI and PCI in different social demographic groups.
Maxillectomy Reconstruction Revision Using Virtual Surgical Planning and Intraoperative Navigation
Authors: Nwagu Uche , Swendseid Brian , Ross Heather , Ganti Rohan , Kane Anne , Curry Joseph M.
Published: April 2021

Secondary revision of osseous flap reconstructions of the maxilla can enhance facial symmetry, but can be challenging due to the absence of normal anatomy and landmarks. We report four cases of maxillectomy reconstruction with scapula tip flap employing a novel combined approach with preoperative virtual surgical planning (VSP) and intraoperative navigation (ION) for secondary revision. VSP was employed to superimpose mirrored normal anatomy upon the reconstructed anatomy, and ION used for real‐time intraoperative anatomical mapping. VSP and ION can be used to optimize maxillary bony revisions and recontouring, thereby improving anatomic symmetry and funtionality. Laryngoscope, 131:E2655–E2659, 2021
Neuroanatomic Volume Differences in Tinnitus and Hearing Loss
Authors: Yousef Andrew , Hinkley Leighton B. , Nagarajan Srikantan S. , Cheung Steven W.
Published: April 2021

Objectives

To investigate neuroanatomic volume differences in tinnitus and hearing loss.

Study Design

Cross‐sectional.

Methods

Sixteen regions of interest (ROIs) in adults (43 male, 29 female) were examined using 3Tesla structural magnetic resonance imaging in four cohorts: 1) tinnitus with moderate hearing loss (N = 31), 2) moderate hearing loss only (N = 15), 3) tinnitus with normal hearing (N = 17), and 4) normal hearing only (N = 13). ROI volumes were corrected for brain size, age, and sex variations. Analysis of covariance (ANCOVA) and post hoc Tukey's test were used to isolate the effects of tinnitus and hearing loss on volume differences. Effect sizes were calculated as the fraction of total variance (η2) in ANCOVA models and percent of mean volume difference relative to mean total volume.

Results

The four cohort ANCOVA revealed tinnitus and hearing loss cohorts to have increased volume in the corona radiata (η2 = 0.192; P = .0018) and decreased volume in the nucleus accumbens (η2 = 0.252; P < .0001), caudate nucleus (η2 = 0.188; P = .002), and inferior fronto‐occipital fasciculus (η2 = 0.250; P = .0001). Tinnitus with normal hearing showed decreased volume in the nucleus accumbens (22.0%; P = .001) and inferior fronto‐occipital fasciculus (18.1%; P = .002), and hearing loss only showed increased volume in the corona radiata (10.7%; P = .01) and decreased volume in the nucleus accumbens (22.1%; P = .001), caudate nucleus (16.1%; P = .004), and inferior fronto‐occipital fasciculus (18.3%; P = .003).

Conclusion

Tinnitus and hearing loss have overlapping effects on neurovolumetric alterations, especially impacting the nucleus accumbens and inferior fronto‐occipital fasciculus. Neurovolumetric studies on tinnitus or hearing loss can be more complete by accounting for those two clinical dimensions separately and jointly.

Level of Evidence

3 Laryngoscope, 131:1863–1868, 2021
A geo‐spatial approach to assess Trees outside Forest (ToF) in Haryana State, India
Authors: Kumar Mothi , Kumar Ritesh , Bishnoi Promila , Sihag Vikas , Bishnoi Ravikant , Rani Seema , Sindhu Partibha , Budhwar Sarika , Kumar Parmod , Sharma Shashikant , Sharma Poonam , Sharma Ritu , Pandey Venketeswar , Dahiya Meenakshi , Arya Virender Singh , Singh Tajinder Pal , Kumar Vinod
Published: April 2021

Mapping and monitoring the Trees outside Forest (ToF) is gaining significance in the scientific community as they provide critical ecosystem services such as protecting soil and water resources, wildlife habitat, and aesthetics including food, fuel, and fibre. Quantifying ToF can also provide useful information for emission estimation relating to the agriculture, forests, and other land use (AFOLU) category of the Intergovernmental Panel for Climate Change (IPCC). Despite the importance of quantifying ToF, very few studies have attempted to quantify them in India's natural resource inventory programs. In this study, we focused on Haryana State, India, to inventory ToF using very high‐resolution (VHR) Indian Remote Sensing (IRS) satellite data. Haryana's landscape is interspersed with croplands and ToF, thus providing a challenging environment to test VHR satellite data's ability to quantify the diversified landscape structure. We specifically used CARTOSAT‐1 panchromatic (2.5 m) and multispectral LISS‐IV (5.8 m) datasets to quantify the vegetation and build a much‐needed database for ToF. We used a novel classification scheme based on the geometry, that is, point, line, or polygon formations, to quantify ToF at a scale of 1:10,000. The obtained results suggest ToF with linear and block formations extended to 128.83 and 20.51  km2, respectively, accounting for ~3.38% of the Total Georgraphical Area of Haryana State while point formations established 2,774,531 in numbers. This study highlights the usefulness of VHR satellite data and fused imagery to quantify ToF in highly diverse landscape of Haryana. The results will help address vital ecosystem services from ToF, including greenhouse gas emissions quantification from the Agriculture, Forests and Other LandUse (AFOLU) category.
Clinical manifestations of hereditary angioedema and a systematic review of treatment options
Authors: Rosi‐Schumacher Mattie , Shah Sejal J. , Craig Timothy , Goyal Neerav
Published: April 2021

Objective

This study systematically reviews the existing literature on the management of hereditary angioedema (HAE) and provides an update on the clinical presentation and specific therapies.

Methods

A literature search of PubMed and Embase databases was conducted from start of the database to February 2021. Inclusion criteria included relevant systematic reviews, randomized control clinical trials, prospective and retrospective cohort studies, and outcomes research published in English and available in full‐text. Out of 310 candidate articles, a total of 55 articles were included in our study.

Results

The most common genetic form of HAE in up to 85% of cases is caused by low levels of C1 esterase inhibitor (C1‐INH) protein, leading to a bradykinin‐mediated increase in vascular permeability. During an attack of HAE, abortive treatment with C1‐INH replacement is most commonly described, however, icatibant, ecallantide, or fresh frozen plasma are also used. Long‐term prophylaxis in the form of C1‐INH replacement (subcutaneous or intravenous), monoclonal antibodies targeting plasma kallikrein, attenuated androgens, and transexemic acid should be considered for those who suffer from frequent, severe attacks.

Conclusion

Progressively distal involvement of the upper airway, especially the larynx, has been shown to pose an increased risk of asphyxiation and death in the acute presentation of HAE. Evaluation by an otolaryngologist is often sought during the emergent clinical management of HAE; therefore, it is prudent that the consulting physician is well‐versed in the prompt recognition, triage of patients, and appropriate treatment modalities.

Level of Evidence

1A.
Sulfate reduction and methanogenesis in the hypersaline deep waters and sediments of a perennially ice‐covered lake
Authors: Saxton Matthew A. , Samarkin Vladimir A. , Madigan Michael T. , Bowles Marshall W. , Sattley William Matthew , Schutte Charles A. , Joye Samantha B.
Published: April 2021

Documenting anaerobic microbial metabolisms in hypersaline perennially ice‐covered lakes in Antarctica further refines the environmental limits to life and may reveal rare biogeochemical mechanisms and/or novel microbial catalysts of elemental cycling. We assessed rates of sulfate reduction, methanogenesis, and anaerobic oxidation of methane using radiotracers and generated 16S rRNA gene libraries from the microbial communities inhabiting the deep calcium‐chloride‐rich brine and sediments of Lake Vanda, McMurdo Dry Valleys, Antarctica. Sulfate reduction rates were observed in surface sediments but not in the brine overlying the sediments. Methane formation through the methylotrophic, acetoclastic, and hydrogenotrophic pathways was quantified using 14C‐labeled methylamine, acetate, and CO2, respectively, and methanogenesis was detected in both the brine and the sediments. Hydrogenotrophic methanogenesis rates were the highest of all substrates tested in the sediments, while methylotrophic methanogenesis was highest in the brines. Anaerobic oxidation of methane was below the limit of detection in both the brines and sediments. The major taxa of Bacteria and Archaea detected were most similar to organisms previously observed in hypersaline environments and included examples related to known sulfate‐reducing bacteria other than Deltaproteobacteria (surprisingly, sulfate‐reducing Deltaproteobacteria were not observed in this study), and both methanogenic and methanotrophic Archaea. These data indicate an active microbial community in the anoxic brine of Lake Vanda that while similar in terms of community structure and metabolism to other brine habitats, is uniquely evolved to survive in this extreme environment.
A coastal N2 fixation hotspot at the Cape Hatteras front: Elucidating spatial heterogeneity in diazotroph activity via supervised machine learning
Authors: Selden Corday R. , Chappell P. Dreux , Clayton Sophie , Macías‐Tapia Alfonso , Bernhardt Peter W. , Mulholland Margaret R.
Published: April 2021

In the North Atlantic Ocean, dinitrogen (N2) fixation on the western continental shelf represents a significant fraction of basin‐wide nitrogen (N) inputs. However, the factors regulating coastal N2 fixation remain poorly understood, in part due to sharp physico‐chemical gradients and dynamic water mass interactions that are difficult to constrain via traditional oceanographic approaches. This study sought to characterize the spatial heterogeneity of N2 fixation on the western North Atlantic shelf, at the confluence of Mid‐ and South Atlantic Bight shelf waters and the Gulf Stream, in August 2016. Rates were quantified using the 15N2 bubble release method and used to build empirical models of regional N2 fixation via a random forest machine learning approach. N2 fixation rates were then predicted from high‐resolution CTD and satellite data to infer the variability of its depth and surface distributions, respectively. Our findings suggest that the frontal mixing zone created conditions conducive to exceptionally high N2 fixation rates (> 100 nmol N L−1 d−1), which were likely driven by the haptophyte‐symbiont UCYN‐A. Above and below this hotspot, N2 fixation rates were highest on the shelf due to the high particulate N concentrations there. Conversely, specific N2 uptake rates, a biomass‐independent metric for diazotroph activity, were enhanced in the oligotrophic slope waters. Broadly, these observations suggest that N2 fixation is favored offshore but occurs continuously across the shelf. Nevertheless, our model results indicate that there is a niche for diazotrophs along the coastline as phytoplankton populations begin to decline, likely due to exhaustion of coastal nutrients.
Sea urchin microbiomes vary with habitat and resource availability
Authors: Miller Paige M. , Lamy Thomas , Page Henry M. , Miller Robert J.
Published: April 2021

Sea urchins are key grazers in coastal seas, where they can survive a variety of conditions and diets, enhancing their ecological impact on kelp forests and other ecosystems. Using 16S rRNA gene sequencing, we characterized bacterial communities associated with guts of the two dominant sea urchin species in southern California, the red urchin Mesocentrotus franciscanus, and the purple urchin Strongylocentrotus purpuratus. Our results show that the two urchin species have distinct gut microbiomes that vary with habitat. The taxonomic composition of their microbiomes suggests that they may facilitate digestion of food and be a source of nutrition themselves. These results highlight the role of microbiomes within macroorganisms as an extended ecological trait, and suggest that microbes may be crucial to resource use and partitioning in co‐occurring species.
The analysis of 226Ra in 1‐liter seawater by isotope dilution via single‐collector sector‐field ICP‐MS
Authors: Vieira Lúcia H. , Geibert Walter , Stimac Ingrid , Koehler Dennis , Rutgers van der Loeff Michiel M.
Published: April 2021

The precise determination of radium‐226 (226Ra) in environmental samples is challenging due to its low concentration. Seawater typically contains between 0.03 and 0.1 fg g−1 226Ra. Thus, this work addresses the need for an easy and precise methodology for 226Ra determination in seawater that may be applied routinely to a large number of samples. For this reason, a new analytical approach has been developed for the quantification of 226Ra in seawater via inductively coupled plasma mass spectrometry (ICP‐MS). Analysis by single collector sector‐field ICP‐MS was shown to be convenient and reliable for this purpose once potential molecular interferences were excluded by a combination of chemical separation and intermediate mass resolution analysis. The proposed method allows purification of Ra from the sample matrix based on preconcentration by MnO2 precipitation, followed by two‐column separation using a cation exchange resin and an extraction chromatographic resin. The method can be applied to acidified and unacidified seawater samples. The recovery efficiency for Ra ranged between 90% and 99.8%, with precision of 5%, accuracy of 95.7% to 99.9%, and a detection limit of 0.033 fg g−1 (referring to the original concentration of seawater). The method has been applied to measure 226Ra concentrations from the North Sea and validated by analyzing samples from the central Arctic (GEOTRACES GN04). Samples from a crossover station (from GEOTRACES GN04 and GEOTRACES GN01 research cruises) were analyzed using alternative methods, and our results are in good agreement with published values.
Polymeric Nanoreactors as Emerging Nanoplatforms for Cancer Precise Nanomedicine
Authors: Li Xin , Zhao Xiaopeng , Lv Runkai , Hao Linhui , Huo Fengwei , Yao Xikuang
Published: April 2021

How to precisely detect and effectively cure cancer which is defined as precise nanomedicine has drawn great attention worldwide. Polymeric nanoreactors which can in situ catalyze inert species into activated ones, can greatly increase imaging quality and enhance therapeutic effects along with decreased background interference and reduced serious side effects. After a brief introduction, the design and preparation of polymeric nanoreactors are discussed from the following aspects, that is, solvent‐switch, pH‐tuning, film rehydration, hard template, electrostatic interaction, and polymerization‐induced self‐assembly (PISA). Subsequently, the biomedical applications of these nanoreactors in the fields of cancer imaging, cancer therapy, and cancer theranostics are highlighted. The last but not least, conclusions and future perspectives about polymeric nanoreactors are given. It is believed that polymeric nanoreactors can bring a great opportunity for future fabrication and clinical translation of precise nanomedicine.
First‐order undefinability of the notion of transfinitely uplifting cardinals
Authors: Fujimoto Kentaro
Published: April 2021

Audrito and Viale introduced the new large cardinal notion of an (α)‐uplifting cardinal (for an ordinal α). We shall show that this notion cannot be defined (or expressed) in the standard first‐order language of set theory for every tranfinite α.
Sulfophenylated Poly (Ether Ether Ketone Ketone) Nanofiber Composite Separator with Excellent Electrochemical Performance and Dimensional Thermal Stability for Lithium‐Ion Battery via Electrospinning
Authors: Hu Wei , Liang Xiaoxiao , Yang Xue , You Yingxue , Zhao Qi , Liu Baijun , Sun Zhaoyan , Men Yongfeng , Zhu Guangshan , Xie Haiming
Published: April 2021

In this investigation, the sulfophenylated poly (ether ether ketone ketone) (SPEEKK) separators for lithium‐ion batteries (LIBs) are prepared via electrospinning. The electrospun sulfophenylated poly (ether ether ketone ketone) membranes (es‐SP) are then modified with lithium bis(trifuoro‐methanesulfonyl)imide (LiTFSI) by immersing in the LiTFSI/ethanol solution to obtain the modified es‐SP composite separators (es‐SP‐Li). SPEEKK displays excellent dimensional thermal stability, and thus the thermal shrinkage of es‐SP‐Li‐20 (20% of LiTFSI in ethanol) composite separators is only 2% after 0.5 h at 200 °C. The strong polarity of sulfonic acid groups on SPEEKK and LiTFSI enhances the electrolyte wettability and uptake, and thus afford more Li source, so as to promote the conductivity of lithium ions in the composite separators, which in turn exhibit positive impacts on the rate and cycling stability performance of LIBs. The Li//LiFePO4 cells assembled with es‐SP‐Li‐20 separator demonstrate excellent electrochemical stability over 170 cycles at 0.2 C with a reversible discharge capacity of 153 mAh g−1, and a promising rate capacity at 2 C. In short, the as‐prepared es‐SP‐Li composite separators with excellent comprehensive property emerge as a promising application in LIBs.
How Do I Rehabilitate Patients with Cervical Dystonia Remotely?
Authors: Castagna Anna , Saibene Enrico , Ramella Marina
Published: April 2021

In literature there is a growing evidence that in cervical dystonia (CD) rehabilitation, both in person and remotely, is an efficacious add on treatment to botulinum neurotoxins (BoNT) injections, but there is no consensus about protocols. We present here two rehabilitation programs implemented by our neuro‐rehabilitative multidisciplinary team. The enclosed video clips show exercises to be performed at home as self‐rehabilitation program, and exercises presented by a physiotherapist for a telerehabilitation program. These two protocols may be helpful for integrating rehabilitation with BoNT treatment in CD.
Whole‐exome sequencing analysis in 10 families of sporadic microtia with thoracic deformities
Authors: Yang Meirong , Lu Xiaosheng , Zhang Ye , Wang Changchen , Cai Zhen , Li Zhengyong , Pan Bo , Jiang Haiyue
Published: April 2021

Background

Microtia is a congenital malformation of the external ear and may occur as an isolated deformity or as part of a syndrome. Our previous study found a high correlation between microtia and thoracic deformities, thus, we propose that external ear and thorax development may be regulated by certain genes in common.

Methods

We performed exome sequencing on 10 families of sporadic microtia with thoracic abnormalities. We identified mutated genes under different models of inheritance, and checked them through Mouse Genome Informatics and association analysis.

Results

We identified 45 rare mutations, including 9 de novo mutations, 20 heterozygous mutations, 3 homozygous mutations, and 13 hemizygous mutations, of which 2 are likely to be causative. They are de novo missense variant in PHF5A and compound heterozygous mutations in CYP26B1, of which CYP26B1 mutation is highly likely pathogenic.

Conclusion

The results indicate that certain genes may affect both external ear and thorax development, and demonstrate the benefits of whole‐exome sequencing in identifying candidate genes of microtia. This study provides a new way for genetic exploration in microtia.
Founder mutation in the PMM2 promotor causes hyperinsulinemic hypoglycaemia/polycystic kidney disease (HIPKD)
Authors: Islam Sumaya , Tekman Mehmet , Flanagan Sarah E. , Guay‐Woodford Lisa , Hussain Khalid , Ellard Sian , Kleta Robert , Bockenhauer Detlef , Stanescu Horia , Iancu Daniela
Published: April 2021

Background

Polycystic kidney disease with hyperinsulinaemic hypoglycaemia (HIPKD) is a recently described disease caused by a single nucleotide variant, c.‐167G>T, in the promoter region of PMM2 (encoding phosphomannomutase 2), either in homozygosity or compound heterozygosity with a pathogenic coding variant in trans. All patients identified so far are of European descent, suggesting a possible founder effect.

Methods

We generated high density genotyping data from 11 patients from seven unrelated families, and used this information to identify a common haplotype that included the promoter variant. We estimated the age of the promoter mutation with DMLE+ software, using demographic parameters corresponding to the European population.

Results

All patients shared a 0.312 Mb haplotype which was absent in 503 European controls available in the 1000 Genomes Project. The age of this mutation was estimated as 105–110 generations, indicating its occurrence around 600 BC, a time of intense migration, which might explain the presence of the same mutations in Europeans around the globe.

Conclusion

The shared unique haplotype among seemingly unrelated patients is consistent with a founder effect in Europeans.
Novel HEXA variants in Korean children with Tay–Sachs disease with regression of neurodevelopment from infancy
Authors: Park Ji Hong , Ko Jung Min , Kim Min Sun , Kim Man Jin , Seong Moon‐Woo , Yoo Taekyeong , Lim Byung Chan , Chae Jong‐Hee
Published: April 2021

Background

Tay–Sachs disease (TSD) is a lysosomal storage disease caused by mutations in the HEXA gene that encodes the HexosaminidaseA (HEXA) enzyme. As HEXA normally functions to degrade the protein GM2‐ganglioside in lysosomes, decreased levels of HEXAcauses an accumulation of the protein and leads to neurological toxicity. Typical clinical manifestations of TSD include neurodevelopmental regression, muscle weakness, hypotonia, hyperreflexia, ataxia, seizures, and other neurological symptoms. It is quite rare in Asian populations, wherein only two cases have been reported in Korea to date.

Methods

Clinical records, radiological assessments, and laboratory findings, such as plasma hexosaminidase assay and HEXA analysis, were extracted from the medical records of three (1 male and 2 female) independent Korean children with infantile form of Tay–Sachs disease.

Results

All three children presented with neurodevelopmental regression and strabismus at around 8 months of age. Presence of cherry‐red spots in the macula led to conduction of biochemical and genetic studies for TSD confirmation. The plasma hexosaminidase assay revealed decreased HEXA activity and low to normal total hexosaminidase activity. Similarly, genetic analysis revealed 4 variants from 6 alleles, including 2 previously reported and 2 novel variants, in the HEXA gene.

Conclusion

We presented three Korean children, who were recently diagnosed with infantile‐type TSDvia enzyme assay and genetic analysis. Furthermore, results showed that fundus examination can be helpful for early diagnosis of children with neurodevelopmental regression.