bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypokinetic hypertrophic cardiomyopathy: clinical phenotype, genetics, and prognosis
Authors: Wasserstrum Yishay , Larrañaga‐Moreira José M. , Martinez‐Veira Cristina , Itelman Edward , Lotan Dor , Sabbag Avi , Kuperstein Rafael , Peled Yael , Freimark Dov , Barriales‐Villa Roberto , Arad Michael
Published: April 2022

Aims

To describe the phenotype, genetics, and events associated with the development of hypertrophic cardiomyopathy (HCM) with reduced ventricular function (HCMr). Heart failure in HCM is usually associated with preserved ejection fraction, yet some HCM patients develop impaired systolic function that is associated with worse outcomes.

Methods and results

Our registry included 1328 HCM patients from two centres in Spain and Israel. Patients with normal baseline ventricular function were matched, and a competing‐risk analysis was performed to find factors associated with HCMr development. Patient records were reviewed to recognize clinically significant events that occurred closely before the development of HCMr. Genetic data were collected in patients with HCMr. A composite of all‐cause mortality or ventricular assist device (VAD)/heart transplantation was assessed according to ventricular function. Median age was 56, and 34% were female patients. HCMr at evaluation was seen in 37 (2.8%) patients, and 46 (3.5%) developed HCMr during median follow up of 9 years. HCMr was associated with younger age of diagnosis, poor functional class, and ventricular arrhythmia. Atrial fibrillation, pacemaker implantation, and baseline left ventricular ejection fraction (LVEF) of ≤55% were significant predictors of future HCMr development, while LV obstruction predicted a lower risk. Genetic testing performed in 53 HCMr patients, identifying one or more pathogenic variant in 38 (72%): most commonly in myosin binding protein C (n = 20). Six of these patients had an additional pathogenic variant in one of the sarcomere genes. Patients with baseline HCMr had a higher risk (hazard ratio 6.4, 4.1–10.1) for the composite outcome and for the individual components. Patients who developed HCMr in the course of the study had similar mortality but a higher rate of VAD/heart transplantation compared with HCM with normal LVEF.

Conclusions

Hypertrophic cardiomyopathy with reduced ejection fraction is associated with heart failure and poor outcome. Arrhythmia, cardiac surgery, and device implantation were commonly documented prior to HCMr development, suggesting they may be either a trigger or the result of adverse remodelling. Future studies should focus on prediction and prevention of HCMr.
Cardiac remodelling – Part 2: Clinical, imaging and laboratory findings. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology
Authors: Aimo Alberto , Vergaro Giuseppe , González Arantxa , Barison Andrea , Lupón Josep , Delgado Victoria , Richards A Mark , de Boer Rudolf A. , Thum Thomas , Arfsten Henrike , Hülsmann Martin , Falcao‐Pires Inês , Díez Javier , Foo Roger S.Y. , Chan Mark Yan Yee , Anene‐Nzelu Chukwuemeka G. , Abdelhamid Magdy , Adamopoulos Stamatis , Anker Stefan D. , Belenkov Yuri , Ben Gal Tuvia , Cohen‐Solal Alain , Böhm Michael , Chioncel Ovidiu , Jankowska Ewa A. , Gustafsson Finn , Hill Loreena , Jaarsma Tiny , Januzzi James L. , Jhund Pardeep , Lopatin Yuri , Lund Lars H. , Metra Marco , Milicic Davor , Moura Brenda , Mueller Christian , Mullens Wilfried , Núñez Julio , Piepoli Massimo F. , Rakisheva Amina , Ristić Arsen D. , Rossignol Patrick , Savarese Gianluigi , Tocchetti Carlo G. , van Linthout Sophie , Volterrani Maurizio , Seferovic Petar , Rosano Giuseppe , Coats Andrew J.S. , Emdin Michele , Bayes‐Genis Antoni
Published: April 2022

In patients with heart failure, the beneficial effects of drug and device therapies counteract to some extent ongoing cardiac damage. According to the net balance between these two factors, cardiac geometry and function may improve (reverse remodelling, RR) and even completely normalize (remission), or vice versa progressively deteriorate (adverse remodelling, AR). RR or remission predict a better prognosis, while AR has been associated with worsening clinical status and outcomes. The remodelling process ultimately involves all cardiac chambers, but has been traditionally evaluated in terms of left ventricular volumes and ejection fraction. This is the second part of a review paper by the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology dedicated to ventricular remodelling. This document examines the proposed criteria to diagnose RR and AR, their prevalence and prognostic value, and the variables predicting remodelling in patients managed according to current guidelines. Much attention will be devoted to RR in patients with heart failure with reduced ejection fraction because most studies on cardiac remodelling focused on this setting.
Pathological findings of clinically suspected myocarditis temporally associated with COVID‐19 vaccination
Authors: Yamamoto Masayoshi , Tajiri Kazuko , Ayuzawa Syogo , Ieda Masaki
Published: April 2022

Reports on the pathological findings of patients with myocarditis after coronavirus disease 2019 (COVID‐19) vaccination are limited. We present a case series of four patients with clinically suspected myocarditis temporally associated with COVID‐19 vaccination who underwent endomyocardial biopsy with no evidence of viral genomes in tissue specimens. Two patients had fulminant myocarditis with marked inflammatory cell infiltration comprised mostly of CD8+ T‐cells and macrophages, and the other two had suspected myocarditis based on the biochemical evidence of myocardial injury and ST changes on an electrocardiogram. However, they did not meet the histological criteria of myocarditis. Immunosuppressive therapy effectively reduced myocardial damage, and all four patients had improved clinical courses. Temporal association does not prove causation, and it cannot be excluded that the two biopsy‐proven cases reported are simply a random association of a naturally occurring virus‐negative immune‐mediated lymphocytic myocarditis occurring after vaccination.
The economic value of grassland ecosystem services: A global meta‐analysis
Authors: Liu Huifang , Hou Lingling , Kang Nannan , Nan Zhibiao , Huang Jikun
Published: April 2022

Background

Grasslands provide a wide variety of ecosystem services that contribute to human wellbeing. While an increasing number of studies are evaluating the monetary value of grassland ecosystem services, most of them focus on specific grassland ecosystem services at regional or local scales, and they use different assessment methods.

Methods

This paper provides a comprehensive assessment of the economic value of global grassland ecosystem services based on a meta‐analysis of 702 observations from 134 primary studies.

Results

The economic values of different ecosystem services cover a wide range of grassland types, regions, and estimation methods. The annual economic value per hectare ranges from $3955 for semidesert grasslands to $5466 for tropical grasslands. On average, regulating services have the highest value, which is approximately four times that of provisioning services or approximately eight times that of food supply services. Several factors impact the estimated ecosystem service values, including the evaluation method, source and year of publication, and study site. The results indicate that the annual economic value of global grasslands exceeds $20.8 trillion.

Conclusions

The findings of this study not only provide useful information for understanding the economic value of various ecosystem services associated with different types of grasslands but also have important policy implications for the ecological conservation of grassland globally.
Mechanisms connecting insomnia to hopelessness among Chinese older adults: Serial mediating roles of fatigue and social support
Authors: Chang Qingsong , Lai Dongpeng , Fu Yuanyuan
Published: April 2022

Background

Hopelessness and insomnia remain growing mental health issues worldwide, their relationship has been neglected by international development policies, especially in the countries with rapidly aging population like China. However, there is little conclusive evidence on the mechanisms through which insomnia severity influences hopelessness. Based on previous research regarding the significant associations among fatigue, social support, insomnia and hopelessness, this study aims to investigate the relationship between insomnia and hopelessness as well as how insomnia affects hopelessness through fatigue and social support.

Methods

A population‐based data including 946 community‐dwelling older adults extracted from “Elderly Care Household Survey in 2019” in Beijing were used. The age of the participants ranged from 66 to 97 years old, and 53.3% of the respondents were female. Intercorrelations among insomnia, fatigue, social support and hopelessness were examined. Serial multiple mediation models were analyzed by the bootstrapping method to assess whether fatigue and social support serially mediate the relationship between insomnia and hopelessness.

Results

Higher level of insomnia severity (coefficient = 0.0421, p < 0.001), higher level of fatigue (coefficient = 0.0171, p < 0.001), and lower level of social support (coefficient = −0.0320, p < 0.001) were significantly associated with higher level of hopelessness. Fatigue and social support in serial, mediated the relationship between insomnia and hopelessness (total effect: coefficient = 0.0623, 95% CI [0.0466, 0.0780]; total direct effect: coefficient = 0.0421, 95% CI [0.0262, 0.0581]; total indirect effect: coefficient = 0.0202, 95% CI [0.0147, 0.0272]).

Conclusions

Improving sleep quality and eliminating fatigue could effectively alleviate the sense of hopelessness among Chinese older adults. In addition, establishing stronger social support brought by social network from family and friends could confer resilience against the negative effects of despair brought by insomnia. Our findings highlighted the mechanism connecting insomnia to hopelessness, which would inspire the future practice.
Efficacy and toxicity of weekly paclitaxel, carboplatin, and cetuximab as induction chemotherapy or in cases of metastases or relapse for head and neck cancer with a focus on elderly or frail patients
Authors: Forman Rebecca , Deshpande Hari , Burtness Barbara , Bhatia Aarti K.
Published: April 2022

Background

Paclitaxel, carboplatin, and cetuximab (PCC) has shown promise as induction chemotherapy and in patients with metastatic/recurrent head and neck cancer (HNC). Given its tolerability, the regimen is used in frail and elderly patients.

Methods

Software generated the cohort of adult patients with HNC treated with PCC in 2014–2019. Modified RECIST response rate (RR), progression‐free survival (PFS), and overall survival (OS) were calculated for the metastatic/recurrent group, and successful induction rate and RR for the induction group. These were also calculated in the elderly/frail subset (EF): age ≥75, performance status ≥2, albumin <3.5.

Results

Fifty‐two percent of patients experienced ≥grade 3 toxicities. For metastatic/recurrent disease (N = 58), RR was 22%, mean PFS was 7.1 months. Mean OS was 15.2 months. In the induction cohort (N = 22), 86% reached their endpoint. The RR was 64%. There were no significant differences for EF.

Conclusions

PCC is well‐tolerated with good induction success rate and reasonable PFS/OS in metastatic/recurrent disease.
Laryngotracheal stenosis: Mechanistic review
Authors: Carpenter Delaney J. , Hamdi Osama A. , Finberg Ariel M. , Daniero James J.
Published: April 2022

Background

The purpose of this review article is to summarize the existing literature surrounding wound healing mechanisms in laryngotracheal stenosis.

Methods

A review of general wound healing pathophysiology, followed by a focused review of iatrogenic laryngotracheal stenosis (iLTS) and idiopathic subglottic stenosis (iSGS) as conditions of aberrant wound healing.

Results

iLTS is the scarring of the laryngotracheal complex, coming secondary to injury from prolonged intubation. iSGS is a chronic fibroinflammatory scarring and narrowing of the subglottic airway in the absence of any obvious preceding injury or trauma. They are both thought to result from a prolonged and dysregulated wound healing response that promotes the deposition of pathologic scar in the airway.

Conclusions

Understanding the mechanisms that underlie wound healing will help identify and intervene on the process early in its development and discover future therapies that target individual wound healing mechanisms limiting the incidence of this recalcitrant disease process.
Ibrutinib, lenalidomide and dexamethasone in patients with relapsed and/or refractory multiple myeloma: Phase I trial results
Authors: Ailawadhi Sikander , Parrondo Ricardo D. , Moustafa Muhamad Alhaj , LaPlant Betsy R. , Alegria Victoria , Chapin Dustin , Roy Vivek , Sher Taimur , Paulus Aneel , Chanan‐Khan Asher A.
Published: April 2022

Therapeutic strategies that target novel pathways are urgently needed for patients with relapsed/refractory multiple myeloma (RRMM). Ibrutinib is an oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in MM cells. This phase 1 dose‐escalation study examined various doses of ibrutinib in combination with standard doses of lenalidomide (25 mg) and dexamethasone (40 mg) using a standard 3 + 3 design in RRMM patients. The primary objective was to determine the maximum tolerated dose (MTD) of ibrutinib in combination with lenalidomide and dexamethasone. Patients (n = 15) had received a median of 4 prior regimens, 53% were triple‐class exposed, 33% were penta‐exposed, and 54% were lenalidomide‐refractory. The MTD of ibrutinib was 840 mg (n = 6) and only 1 dose‐limiting toxicity; a grade 3 rash possibly related to ibrutinib was noted. The most common ≥ grade 3 adverse events were rash in 2 (13%), lymphopenia in 2 (13%), leukopenia, neutropenia, thrombocytopenia, and anemia all occurring in 3 (20%) patients each. One patient achieved a partial response for an overall response rate of 7%. The clinical benefit rate was 80%. The median time to progression was 3.8 months. Ibrutinib, lenalidomide and dexamethasone appears to be a safe and well‐tolerated regimen with reasonable efficacy in heavily pretreated RRMM patients.
Targeting CD19 in diffuse large B‐cell lymphoma: An expert opinion paper
Authors: Bailly Sarah , Cartron Guillaume , Chaganti Sridhar , Córdoba Raul , Corradini Paolo , Düll Johannes , Ferrarini Isacco , Osborne Wendy , Rosenwald Andreas , Sancho Juan‐Manuel , Tilly Hervé , Van Den Neste Eric , Viardot Andreas , Visco Carlo
Published: April 2022

The ubiquitous, early‐stage expression, efficient internalization, limited off‐target effects, and high disease specificity of CD19 make it an attractive therapeutic target. Currently available anti‐CD19 therapies have demonstrated particular promise in patients with relapsed or refractory B‐cell non‐Hodgkin lymphoma. Selection of the most appropriate treatment strategy should be based on individual patient characteristics and the goal of therapy. However, evidence and knowledge about the sequencing of anti‐CD19 therapies are limited. Here, we review the current evidence for CD19 as a target in diffuse large B‐cell lymphoma and consider approaches to the use of anti‐CD19 therapy.
Promoting intramolecular charge transfer of graphitic carbon nitride by donor–acceptor modulation for visible‐light photocatalytic H2 evolution
Authors: Wan Sijie , Xu Jingsan , Cao Shaowen , Yu Jiaguo
Published: April 2022

To satisfy the requirements of substantial green development, it is urgent to explore an innovative eco‐friendly semiconductor photocatalyst to efficiently achieve visible‐light‐driven photocatalytic H2 evolution (PHE). The strategy of promoting the spatial separation efficiency of photoinduced carriers can essentially enhance the PHE performance of a photocatalyst. Herein, a graphitic carbon nitride (g‐C3N4)‐based donor–acceptor (D‐A) copolymer (CNDMx) is constructed by simple one‐pot thermal polycondensation, using urea and 5,8‐DibroMoquinoxaline (as an electron donor) as precursors. The electron D‐A modulation consequently creates an internal electric field to facilitate the intramolecular charge transfer within the copolymer. A series of experimental characterizations and density functional theory calculations are applied to elucidate the variation and correlation of the structure and PHE performance of the as‐prepared catalysts. It is found that the best average PHE rate of 3012.5 μmol g−1 h−1 can be achieved over the optimal D‐A copolymer under visible‐light (400 < λ < 800 nm) irradiation, which is ~3.3 times that of pure urea‐derived g‐C3N4. The corresponding apparent quantum efficiency is 1.3% at 420 nm. This study provides a protocol for designing effective visible‐light photocatalysts via D‐A modulation of polymeric semiconductors.
Incomplete sagittal septum of the bladder with cystolithiasis
Authors: Fujimoto Takeru , Goto Takayuki , Kanematsu Akihiro , Nishimatsu Hiroaki , Fujimoto Masakazu , Matsuoka Takashi , Kono Jin , Kita Yuki , Masui Kimihiko , Sano Takeshi , Sawada Atsuro , Akamatsu Shusuke , Kobayashi Takashi
Published: April 2022

Introduction

Incomplete sagittal septum of the urinary bladder is an extremely rare congenital anomaly and one of the variations in bladder duplication. Herein, we report a case of incomplete sagittal septum of the bladder with cystolithiasis.

Case presentation

A 20‐year‐old man was referred to our department for examination and treatment of symptomatic cystolithiasis and a suspected giant ureterocele on the left side. Cystoscopy and urography performed under general anesthesia revealed anatomical structures suggestive of the sagittal septum of the bladder. Subsequently, transurethral septostomy and cystolithotripsy were performed. The detrusor muscle was microscopically identified, leading to the diagnosis of an incomplete sagittal septum of the bladder.

Conclusion

Although extremely rare, an incomplete sagittal septum of the bladder may be difficult to differentiate from a ureterocele, and should be considered when a large cystic lesion is found in the bladder.
Compressive‐sensing swept‐source optical coherence tomography angiography with reduced noise
Authors: Wang Lingyun , Chen Ziye , Zhu Zhanyu , Yu Xiaojun , Mo Jianhua
Published: April 2022

Optical coherence tomography angiography (OCTA), as a functional extension of optical coherence tomography (OCT), has exhibited a great potential to aid in clinical diagnostics. Currently, OCTA still suffers from motion artifact and noise. Therefore, in this article, we propose to implement compressive sensing (CS) on B‐scans to reduce motion artifact by increasing B‐scan rate. Meanwhile, a noise reduction filter is specially designed by combining CS, Gaussian filter and median filter. Specially, CS filtering is realized by averaging multiple CS repetitions on en‐face OCTA images with varied sampling functions. The method is evaluated on in vivo OCTA images of human skin. The results show that vasculature structures can be reconstructed well through CS on B‐scans with a sampling rate of 70%. Moreover, the noise can be significantly eliminated by the developed filter. This implies that our method has a good potential to expedite OCTA imaging and improve the image quality.
Soft 3D hybrid network for delivery and controlled release of poorly soluble dihydropyrimidinone compound: An insight into the novel system for potential application in leukemia treatment
Authors: Marković Maja D. , Tadić Julijana D. , Savić Sanja I. , Matić Ivana Z. , Stanojković Tatjana P. , Mijin Dušan Ž. , Panić Vesna V.
Published: April 2022

Researchers are faced with everyday demands for safer and more efficient therapy for many diseases, especially serious one such as various types of cancer. Numerous anticancer drugs are poorly‐water soluble and therefore their encapsulation and controlled release remain quite challenge. In present study, we deepened our research of hydrophilic carrier based on poly(methacrylic acid) and casein (PMAC) by investigating its potential for encapsulation and controlled release of novel poorly water‐soluble dihydropyrimidion‐azo‐pyridon compound (DHPMP). DHPMP is a dye that has been proven to show cytotoxic activity against chronic myeloid leukemia K562 cells. By encapsulating DHPMP into the carrier and delivering it into the intestines, DHPMP absorption could be the fastest and the number of therapeutic doses and side effects can be reduced. Carriers based on PMAC and DHPMP (PMAC‐DHPMP) were synthetized and characterized by FTIR, SEM and single compression tests. The swelling behavior of PMAC‐DHPMP carriers and cumulative DHPMP release were investigated depending on the amount of crosslinker and encapsulated DHPMP in two media which were simulating pH environments in human stomach and intestines. The prolonged and controlled release of DHPMP was achieved. In vitro cytotoxic activity of PMAC‐DHPMP carriers against K562 cells and the cell cycle analysis showed great potential of the carriers for application in leukemia treatment.
Fetal corpus callosum abnormalities: Ultrasound and magnetic resonance imaging role
Authors: Moradi Behnaz , Taherian Reza , Tahmasebpour Ahmad‐Reza , Sanei Taheri Morteza , Kazemi Mohammad Ali , Pak Neda , Shirazi Mahboobeh , Radmanesh Alireza , Oztekin Ozgur , Arab‐Ahmadi Mehran
Published: April 2022

The corpus callosum (CC) is the major interhemispheric commissure and its abnormalities include agenesis, hypoplasia, and hyperplasia. The CC anomalies are typically related to other central nervous system (CNS) or extra‐CNS malformations. The antenatal diagnosis of complete CC agenesis is easy after mid‐trimester by ultrasound (US) even in the axial plane. The non‐visualization of cavum septum pellucidum and colpocephaly are critical signs in the axial view. More subtle findings (i.e., hypoplasia and partial agenesis) might also be recognized antenatally. In this review, the focus was given on the prenatal diagnosis of CC abnormalities in US and magnetic resonance imaging.
Light and scanning electron microscopic comparative studies of geminivirus infected and healthy Eclipta alba (L.)
Authors: Sonia Romisha , Shaheen Shabnum , Khalid Sana , Sharifi‐Rad Javad , Shahid Muhammad Naveed , Mukhtar Hanan , Khalid Zaryab , Harun Nidaa , Hussain Rana Abrar , Khan Farah
Published: April 2022

Eclipta alba (L.) is a valuable medicinal plant. However, its medicinal efficacy can be affected by geminivirus infection. Therefore, identification of healthy specimen is essential before to use as medicine. The present study provided the taxonomic characterization of geminivirus infected and healthy E. alba plant by studying apparent morphology and microscopic features through light and scanning electron microscopy. Before taxonomic characterization infected and healthy specimens were separated through molecular detection of geminivirus. Results of morphological studies reported that geminivirus infected E. alba plant showed systematic symptoms of infection like stunted growth, distortion and chlorosis of leaves, decrease in size of root, shoot and fruit, and so forth in comparison to healthy specimen. Anatomical findings reported that in both plants anomocytic and anisocytic types of stomata with multicellular warty trichomes were present. However, variations were observed in quantitative measures such as size of trichomes, epidermal, subsidiary and guard cells. Palynological observations identifies that both plants possessed tricolporate type of pollen but variation was mainly observed in size and shape of pollen, thickness of exine and intine, P/E ratio, pore size, interspecific difference, size of colpi, and pollen ornamentation. Overall this study concluded that both healthy and infected E. alba do not reported much variations in qualitative taxonomic features, but can be differentiated in terms of quantitative taxonomic evidences. Future studies are recommended for pharmacological analysis of both healthy and virus infected plants.

Research Highlights

Eclipta alba has incredible therapeutic worth, but due to geminivirus infection the plant is affecting badly. Hence, the present studies give a comprehensive taxonomic report on the geminivirus infected and healthy plant species.
Corrosion resistance and surface microstructure of Mg3N2/SS thin films by plasma focus instrument
Authors: Habibi Maryam , Sadeghi Mohammad , Arman Ali , Sobola Dinara , Luna Carlos , Mirzaei Saeed , Zelati Amir , da Fonseca Filho Henrique Duarte , Ţălu Ştefan
Published: April 2022

Utilizing a plasma focus (PF) instrument, magnesium nitride (Mg3N2) thin films were synthesized on stainless steel substrates. Twenty five optimum focus shots at 8 cm distance from the anode tip were used to deposit the films at different angular positions regarded to the anode axis. Scanning electron microscopy (SEM), atomic force microscopy (AFM), and X‐ray diffraction (XRD) analyses were performed to assess the surface morphology and structural characteristics of Mg3N2 films. Based on AFM images, these films were studied to understand the effect of angular position variation on their surfaces through morphological and fractal parameters. By increasing the angle, we verify that the grain size decreased from 130(0) nm to 75(5) nm and also the mean quadratic surface roughness of the films reduced in its average values from (28.97 ± 3.24) nm to (23.10 ± 1.34) nm. Power spectrum density analysis indicated that films become more self‐affine at larger angles. Furthermore, the corrosion behavior of the films was investigated through a potentiodynamic polarization test in H2SO4 solution. It was found that the ion energy and flux, varying with the angular positions from the anode tip, directly affected the nanostructured roughness and surface morphology of the samples. The electrochemical studies of films show that the uncoated sample presented the lowest corrosion resistance. The highest corrosion resistance was obtained for the sample deposited with 25 optimum shots and at 0° angular position reaching a reduction in the corrosion current density of almost 800 times compared to the pure stainless steel‐304 substrate.

Highlights

Mg3N2/SS films have been deposited at different angles by plasma focus (PF) instruments.

The effect of angular position on the surface microtexture, morphological parameters, and corrosion features of the films was studied.

The RBS measurement and X‐ray diffraction are utilized to identify the crystalline phases and thickness of films.
Phase I Randomized Trial of 17O‐Labeled Water: Safety and Feasibility Study of Indirect Proton MRI for the Evaluation of Cerebral Water Dynamics
Authors: Harada Taisuke , Kudo Kohsuke , Kameda Hiroyuki , Sato Ryota , Shirai Toru , Bito Yoshitaka , Fujima Noriyuki , Tsuneta Satonori , Nogawa Toshifumi , Maeda Kenichiro , Hayashi Hiroshi , Sasaki Makoto
Published: April 2022

Background

17O‐labeled water (PSO17) is a contrast agent developed to measure brain water dynamics and cerebral blood flow.

Purpose

To evaluate the safety and feasibility of PSO17.

Study Type

Prospective study.

Subjects

A total of 12 male healthy volunteers (23.1 ± 1.9 years) were assigned to three groups of four subjects: placebo (normal saline), PSO17 10%, and PSO17 20%.

Field Strength/Sequence

Dynamic 3D fluid attenuated inversion recovery (FLAIR, fast spin echo with variable refocusing flip angle) scans of the brain were performed with 3‐T MRI.

Assessment

Contrast agents were injected 5 minutes after the start of a 10‐minute scan. Any symptoms, vital signs, and blood and urine tests were evaluated at five timepoints from preinjection to 4 days after. Blood samples for pharmacokinetic analysis, including half‐life (T1/2), maximum fraction (Cmax), time‐to‐maximum fraction (Tmax), and area under the curve (AUC), were collected at 13 timepoints from preinjection to 168 hours after. Regions of interest were set in the cerebral cortex (CC), basal ganglia/thalamus (BG/TM), and white matter (WM), and 17O concentrations were calculated from signal changes and evaluated using Cmax.

Statistical Tests

All items were compared among the three groups using Tukey–Kramer's honestly significant difference test. Statistical significance was defined as P < 0.5.

Results

No safety issues were noted with the intravenous administration of PSO17. The T1/2 was approximately 160 hours, and the AUCs were 1.77 ± 0.10 and 3.75 ± 0.36 in the PSO17 10% and 20% groups, respectively. 17O fractions calculated from MRI signals were higher in the PSO17 20% group than in the 10% and placebo groups. Significant differences were noted between all pairs of groups in the CC and BG/TM, and between PSO17 20% and both placebo and 10% groups in the WM.

Data Conclusion

PSO17 might be considered safe as a contrast medium. Dynamic 3D‐FLAIR might detect dose‐dependent signal changes and estimate 17O.

Evidence Level

1

Technical Efficacy

Stage 1
Diagnostic performance of gliomas grading and IDH status decoding A comparison between 3D amide proton transfer APT and four diffusion‐weighted MRI models
Authors: Guo Hu , Liu Jun , Hu JunJiao , Zhang HuiTing , Zhao Wei , Gao Min , Zhang Yi , Yang Guang , Cui Yan
Published: April 2022

Background

The focus of neuro‐oncology research has changed from histopathologic grading to molecular characteristics, and medical imaging routinely follows this change.

Purpose

To compare the diagnostic performance of amide proton transfer (APT) and four diffusion models in gliomas grading and isocitrate dehydrogenase (IDH) genotype.

Study Type

Prospective.

Population

A total of 62 participants (37 males, 25 females; mean age, 52 ± 13 years) whose IDH genotypes were mutant in 6 of 14 grade II gliomas, 8 of 20 of grade III gliomas, and 4 of 28 grade IV gliomas.

Field Strength/Sequence

APT imaging using sampling perfection with application optimized contrasts by using different flip angle evolutions (SPACE) and DWI with q‐space Cartesian grid sampling were acquired at 3 T.

Assessment

The ability of diffusion kurtosis imaging, diffusion kurtosis imaging, neurite orientation dispersion and density imaging (NODDI), mean apparent propagator (MAP), and APT imaging for glioma grade and IDH status were assessed, with histopathological grade and genetic testing used as a reference standard. Regions of interest (ROIs) were drawn by two neuroradiologists after consensus.

Statistical Tests

T‐test and Mann–Whitney U test; one‐way analysis of variance (ANOVA); receiver operating curve (ROC) and area under the curve (AUC); DeLong test. P value < 0.05 was considered statistically significant.

Results

Compared with IDH‐mutant gliomas, IDH‐wildtype gliomas showed a significantly higher mean, 5th‐percentile (APT5), and 95th‐percentile from APTw, the 95th‐percentile value of axial, mean, and radial diffusivity from DKI, and 95th‐percentile value of isotropic volume fraction from NODDI, and no significantly different parameters from DTI and MAP (P = 0.075–0.998). The combined APT model showed a significantly wider area under the curve (AUC 0.870) for IDH status, when compared with DKI and NODDI. APT5 was significantly different between two of the three groups (glioma II vs. glioma III vs. glioma IV: 1.35 ± 0.75 vs. 2.09 ± 0.93 vs. 2.71 ± 0.81).

Data conclusion

APT has higher diagnostic accuracy than DTI, DKI, MAP, and NODDI in glioma IDH genotype. APT5 can effectively identify both tumor grading and IDH genotyping, making it a promising biomarker for glioma classification.

Evidence Level

1

Technical Efficacy

Stage 2
Atmospheric rivers and associated extreme rainfall over Morocco
Authors: Khouakhi Abdou , Driouech Fatima , Slater Louise , Waine Toby , Chafki Omar , Chehbouni Abdelghani , Raji Otmane
Published: April 2022

Atmospheric rivers (ARs) are long, narrow, and transient corridors of enhanced water vapour content in the lower troposphere, associated with strong low‐level winds. These features play a key role in the global water cycle and drive weather extremes in many parts of the world. Here, we assessed the frequency and general characteristics of landfalling ARs over Morocco for the period 1979–2020. We used ECMWF ERA5 reanalysis data to detect and track landfalling ARs and then assessed AR association with rainfall at the annual and seasonal scales, as well as extreme rainfall events (defined as a daily precipitation amount exceeding the 99th percentile threshold of the wet days) at 30 gauging stations located across Morocco. Results indicate that about 36 ARs/year make landfall in Morocco. AR occurrence varies spatially and seasonally with highest occurrences in the autumn (SON) and Winter (DJF) in the northern part of the country and along the Atlantic across northern regions. AR rainfall climatology indicates up to 180 mm·year−1 recorded in stations located in the northwest. High fractional contributions (~28%) are recorded in the north and the Atlantic regions, with the driest regions of the south receiving about a third of their annual rainfall from ARs. For extreme rainfall, the highest AR contributions can attain over 50% in the southern dry regions and along the Atlantic north coast and Atlas highlands.
The interannual synchronization of the heatwave days in Korea and western North Pacific tropical cyclone genesis frequency
Authors: Cha Yumi , Choi Jae Won , Ahn Joong‐Bae
Published: April 2022

This study conducted a correlation analysis between tropical cyclone genesis frequency (TCGF) in the western North Pacific (WNP) and heatwave days (HWD) in Korea during July and August for 1973–2018 and we found a strong positive correlation between them. This implied that the higher the TCGF in the WNP during July and August, the higher the HWD in Korea becomes. To examine the cause of the positive correlation between the TCGF during July and August in the WNP and the HWD in Korea, 15 years with the highest frequency and the lowest frequency out of the 46 years in the TCGF time series were selected and defined as high TCGF years and low TCGF years, respectively. According to the difference in atmospheric circulations between the two groups, in all layers of the troposphere, anomalous anticyclonic and cyclonic circulations were strengthened in the mid‐latitude region of East Asia and in the WNP, respectively, which was similar to the Pacific‐Japan (PJ) teleconnection pattern. The difference in the vertical meridional circulation averaged over the longitude range where Korea is located showed that anomalous upward and downward flows were strengthened in the WNP and in the latitude where Korea is located, respectively. This implied that the local Hadley circulation was strengthened during high TCGF years. Five hundred hectopascal wave activity flux originated from the North Atlantic, passed through the Scandinavian Peninsula, the North coast of Russia, and East Siberia before reaching Korea and the WNP. This spatial distribution was similar to the Scandinavia teleconnection pattern.
Human synovial fluid interleukin‐6, but not type II collagen breakdown, positively correlated with pain after anterior cruciate ligament injury and reconstruction
Authors: Sullivan Breanna , Stone Austin V. , Conley Caitlin E. W. , Hunt Emily R. , Lattermann Christian , Jacobs Cale A.
Published: April 2022

Anterior cruciate ligament (ACL) injury initiates a biochemical cascade thought to contribute to the onset and progression of posttraumatic osteoarthritis (PTOA). Interleukin‐1ß (IL‐1ß), IL‐6, and C‐telopeptide fragments of type II collagen (CTX‐II) are implicated in joint inflammation and cartilage degradation following ACL injury; however, their association with pain is still being explored. The purpose of this study was to evaluate the associations between synovial fluid concentrations of IL‐1ß, IL‐6, and CTX‐II with pain following ACL injury and reconstruction. We hypothesized that greater IL‐1ß, IL‐6, and CTX‐II would correlate with greater Pain Visual Analogue Scale (VAS) scores. This was a secondary analysis of 23 patients (mean age = 18.4 years, BMI = 27.4, 13 females/10 males) with acute ACL tears who participated in a pilot randomized trial. Synovial fluid and VAS scores were collected on the day of initial presentation, at ACL reconstruction, and 1 and 4 weeks after surgery. Synovial fluid concentrations of IL‐1ß, IL‐6, and CTX‐II were assessed using enzyme‐linked immunoabsorbent assays, and repeated measures correlations were used to assess the relationships between pain and synovial IL‐1ß, IL‐6, or CTX‐II after ACL injury and reconstruction. Pain was positively correlated with synovial fluid IL‐6 concentrations (r = 0.52, p < 0.001); however, pain was inversely correlated with CTX‐II (r = −0.39, p = 0.002). IL‐1ß had no significant correlation with pain. Statement of clinical relevance: PTOA has been described as a “silent killer” and these results suggest that early PTOA may have pro‐inflammatory pathways that are not primarily associated with pain but still lead to progressive cartilage loss.
Peripheral sensitization is demonstrated in subacromial pain syndrome, with central sensitization found only in females
Authors: King Jacqlyn , Shapiro Matthew , Karduna Andrew
Published: April 2022

The objective of this study was to explore whether hypersensitivity in patients with subacromial pain syndrome (SPS) manifests purely as localized peripheral sensitization or central sensitization, is influenced by the presence of subacromial pain, and presents similarly in male and female patients. Pressure pain threshold was assessed in both a patient cohort with unilateral SPS and an uninjured matched control group. Control subjects were assessed twice, with a 15 minute rest period between testing, while patients were assessed at baseline and after an almost instantaneous reduction in pain arising from an anesthetic injection in patients. Patients received a subacromial injection consisting of both anesthetics (3 cc of 2% lidocaine and 6 cc 0.5% Marcaine with Epinephrine) and a corticosteroid agent (1 cc DepoMedrol). Patients demonstrated hypersensitivity across the involved shoulder only, providing evidence for peripheral sensitization. There were trends for hypersensitivity across remote joints, however when separated by sex, only female patients demonstrated both peripheral and central sensitization. Immediate pain reduction had no influence on hypersensitivity in the short‐term. Clinical Significance: Neuropathic components are likely present in some patients with subacromial pain syndrome, and female patients may be particularly at risk for presenting with neuropathic pain. These findings are applicable towards understanding the heterogeneous etiology underlying subacromial pain syndrome and informing clinical management.
Meta‐analysis of dichotomous and ordinal tests with an imperfect gold standard
Authors: Cerullo Enzo , Jones Hayley E. , Carter Olivia , Quinn Terry J. , Cooper Nicola J. , Sutton Alex J.
Published: April 2022

Standard methods for the meta‐analysis of medical tests, without assuming a gold standard, are limited to dichotomous data. Multivariate probit models are used to analyse correlated dichotomous data, and can be extended to model ordinal data. Within the context of an imperfect gold standard, they have previously been used for the analysis of dichotomous and ordinal test data from a single study, and for the meta‐analysis of dichotomous tests. However, they have not previously been used for the meta‐analysis of ordinal tests. In this article, we developed a Bayesian multivariate probit latent class model for the simultaneous meta‐analysis of ordinal and dichotomous tests without assuming a gold standard, which also allows one to obtain summary estimates of joint test accuracy. We fitted the models using the software Stan, which uses a state‐of‐the‐art Hamiltonian Monte Carlo algorithm, and we applied the models to a dataset in which studies evaluated the accuracy of tests, and test combinations, for deep vein thrombosis. We demonstrate the issues with dichotomising ordinal test accuracy data in the presence of an imperfect gold standard, before applying and comparing several variations of our proposed model which do not require the data to be dichotomised. The models proposed will allow researchers to more appropriately meta‐analyse ordinal and dichotomous tests without a gold standard, potentially leading to less biased estimates of test accuracy. This may lead to a better understanding of which tests, and test combinations, should be used for any given medical condition.
Study on phenolic acids of Lonicerae japonicae Flos based on ultrahigh performance liquid chromatography‐tandem mass spectrometry combined with multivariate statistical analysis
Authors: Xiong Lewen , Zhao Hongwei , Wang Yang , Liu Yan , Jin Ying , Zhang Longfei , Zhang Yongqing
Published: April 2022

Lonicerae japonicae Flos, a traditional Chinese medicine, has the function of evacuating heat and detoxifying. To promote the optimization of Lonicerae japonicae Flos germplasms and improve the quality of medicinal materials, 55 batches of five Lonicerae japonicae Flos germplasms with the same origin were collected during different periods, a UHPLC‐TOF‐MS method was established, and 22 kinds of phenolic acids were found and qualitatively analysed. Seventeen phenolic acids were selected for quantitative analysis by UHPLC‐QqQ‐MS/MS, and the quantitative results were analysed by principal component analysis, orthogonal partial least squares‐discriminant analysis, and partial least squares discriminant analysis. The contents of phenolic acids in periods S1–S6 were found to be significantly different. There were also significant differences in the accumulation of phenolic acids in Lonicerae japonicae Flos during different growth periods. Ferulic acid, 5‐O‐caffeoylquinic acid, and caffeic acid were determined to be important components to distinguish the different growth periods of Lonicerae japonicae Flos. There were significant differences in the phenolic acid content of different germplasms of Lonicerae japonicae Flos, and the total amount of 17 phenolic acids and total acids (chlorogenic acid, 3,5‐di‐O‐caffeoylquinic acid, and 4,5‐di‐O‐caffeoylquinic acid) in “Hua Jin No. 6” was highest, so the quality of “Hua Jin No. 6” was better than that of the four other germplasms. In addition, chlorogenic acid methyl ester and caffeic acid were the smallest markers in combination to distinguish the five germplasms of Lonicerae japonicae Flos.
Hybrid Mucin‐Vaterite Microspheres for Delivery of Proteolytic Enzyme Chymotrypsin
Authors: Balabushevich Nadezhda G. , Kovalenko Ekaterina A. , Filatova Lyubov Y. , Kirzhanova Ekaterina A. , Mikhalchik Elena V. , Volodkin Dmitry , Vikulina Anna S.
Published: April 2022

While the enteral delivery of proteolytic enzymes is widely established for combating many diseases as an alternative to antibiotic treatment, their local delivery only emerges as administration route enabling sustained release in a controlled manner on site. The latest requires the development of drug delivery systems suitable for encapsulation and preservation of enzymatic proteolytic activity. This study proposes hybrid microspheres made of mucin and biodegradable porous crystals of calcium carbonate (CC) as the carriers for chymotrypsin (CTR) delivery. CTR is impregnated into CC and hybrid CC/mucin (CCM) microspheres by means of sorption without any chemical modification. The loading of the CC with mucin enhances CTR retention on hybrid microspheres (adsorption capacity of ≈8.7 mg g−1 vs 4.7 mg g−1), recharging crystal surface due to the presence of mucin and diminishing the average pore diameter of the crystals from 25 to 8 nm. Mucin also retards recrystallization of vaterite into nonporous calcite improving stability of CCM microspheres upon storage. Proteolytic activity of CTR is preserved in both CC and CCM microspheres, being pH dependent. Temperature‐induced inactivation of CTR significantly diminishes by CTR encapsulation into CC and CCM microspheres. Altogether, these findings indicate promises of hybrid mucin‐vaterite microspheres for mucosal application of proteases.
Does renting luxury make me shine? The mediating role of perceived signals
Authors: Gong Yanping , Zhang Qin , Zhang Jifei
Published: April 2022

Whether rented luxury creates symbolic meaning for consumers who cannot afford it, thus, providing them with an effective way to construct their identity, similar to owned luxury, and strengthen their willingness to rent. Drawing on implicit self‐theories, we find that compared with entity theorists, incremental theorists have lower willingness to rent luxury products (Studied 1, 2, and 3), but they do not exhibit significant differences in self‐brand connection (Studied 2 and 3). We show that incremental theorists (vs. entity theorists) perceive more authentic signal than symbolic signal regarding their inability to afford luxury goods when using rented luxury products (Study 3). Neither in ownership‐based luxury consumption (Study 4, where there is no authentic signal), nor in access‐based nonluxury consumption (Study 5, where there is no symbolic signal), consumers with different implicit beliefs no longer differentiate in buying/renting intentions. Our work suggests that not all consumers who desire unaffordable luxuries are willing to rent them. Therefore, managers should consider how to reduce the negative impacts of authentic signals on incremental theorists' renting intentions.
Identification of novel arsenic resistance genes in yeast
Authors: Isik Esin , Balkan Çiğdem , Karl Vivien , Karakaya Hüseyin Çağlar , Hua Sansan , Rauch Sebastien , Tamás Markus J. , Koc Ahmet
Published: April 2022

Arsenic is a toxic metalloid that affects human health by causing numerous diseases and by being used in the treatment of acute promyelocytic leukemia. Saccharomyces cerevisiae (budding yeast) has been extensively utilized to elucidate the molecular mechanisms underlying arsenic toxicity and resistance in eukaryotes. In this study, we applied a genomic DNA overexpression strategy to identify yeast genes that provide arsenic resistance in wild‐type and arsenic‐sensitive S. cerevisiae cells. In addition to known arsenic‐related genes, our genetic screen revealed novel genes, including PHO86, VBA3, UGP1, and TUL1, whose overexpression conferred resistance. To gain insights into possible resistance mechanisms, we addressed the contribution of these genes to cell growth, intracellular arsenic, and protein aggregation during arsenate exposure. Overexpression of PHO86 resulted in higher cellular arsenic levels but no additional effect on protein aggregation, indicating that these cells efficiently protect their intracellular environment. VBA3 overexpression caused resistance despite higher intracellular arsenic and protein aggregation levels. Overexpression of UGP1 led to lower intracellular arsenic and protein aggregation levels while TUL1 overexpression had no impact on intracellular arsenic or protein aggregation levels. Thus, the identified genes appear to confer arsenic resistance through distinct mechanisms but the molecular details remain to be elucidated.