bluuebunny/crossref_metadata_2025 huggingface dataset:
High burden of acquired morbidity in survivors of pediatric acute respiratory distress syndrome
Authors: Loh Sin Wee , Gan Ming Ying , Wong Judith Ju‐Ming , Ong Chengsi , Mok Yee Hui , Lee Jan Hau
Published: May 2021

Introduction

With improving mortality rates in pediatric acute respiratory distress syndrome (PARDS), functional outcomes in survivors are increasingly important. We aim to describe the change in functional status score (FSS) from baseline to discharge and to identify risk factors associated with poor functional outcomes.

Methods

We examined clinical records of patients with PARDS admitted to our pediatric intensive care unit (PICU) from 2009 to 2016. Our primary outcome was acquired morbidity at PICU and hospital discharge (defined by an increase in FSS ≥3 points above baseline). We included severity of illness scores and severity of PARDS in our bivariate analysis for risk factors for acquired morbidity.

Results

There were 181 patients with PARDS, of which 90 (49.7%) survived. Median pediatric index of mortality 2 score was 4.05 (1.22, 8.70) and 21 (23.3%) survivors had severe PARDS. A total of 59 (65.6%) and 14 (15.6%) patients had acquired morbidity at PICU and hospital discharge, respectively. Median baseline FSS was 6.00 (6.00, 6.25), which increased to 11.00 (8.75, 12.00) at PICU discharge before decreasing to 7.50 (6.00, 9.25) at hospital discharge. All patients had significantly higher FSS at both PICU and hospital discharge median compared to baseline. Feeding and respiratory were the most affected domains. After adjusting for severity of illness, severity categories of PARDS were not a risk factor for acquired morbidity.

Conclusion

Acquired morbidity in respiratory and feeding domains was common in PARDS survivors. Specific attention should be given to these two domains of functional outcomes in these children.
An unusual case of intervertebral disc extrusion in a dog
Authors: Santifort Koen , Pijnenburg Jeanette , Beukers Martijn , Bergmann Wilhelmina , Bergknut Niklas
Published: May 2021

A 6‐year‐old castrated male Dachshund‐cross was presented with signs compatible with a thoracolumbar myelopathy. MRI findings were considered most consistent with neoplasia as a large, oval‐shaped, well‐defined extradural mass with atypical intensity presentation was found in the spinal canal with extension into the intervertebral foramen. Owners elected euthanasia and post‐mortem histopathological examination resulted in a final diagnosis of compressive myelopathy due to extrusion of degenerated nucleus pulposus with haemorrhage and secondary encapsulation of the compressive material by fibroblasts. This case illustrates the variable appearance of intervertebral disc extrusion on MRI.
Hydroelastic interaction of nonlinear waves with floating sheets
Authors: Kostikov Vasily , Hayatdavoodi Masoud , Ertekin R. Cengiz
Published: May 2021

Hydroelastic responses of floating elastic surfaces to incident nonlinear waves of solitary and cnoidal type are studied. There areNnumber of the deformable surfaces, and these are represented by thin elastic plates of variable properties and different sizes and rigidity. The coupled motion of the elastic surfaces and the fluid are solved simultaneously within the framework of linear beam theory for the structures and the nonlinear Level I Green–Naghdi theory for the fluid. The water surface elevation, deformations of the elastic surfaces, velocity and pressure fields, wave reflection and transmission coefficients are calculated and presented. Results of the model are compared with existing laboratory measurements and other numerical solutions. In the absence of any restriction on the nonlinearity of the wave field, number of surfaces, their sizes and rigidities, a wide range of wave–structure conditions are considered. It is found that wave reflection from an elastic surface changes significantly with the rigidity, and the highest reflection is observed when the plate is rigid (not elastic). It is also found that due to the wave–structure interaction, local wave fields with different length and celerity are formed under the plates. In the case of multiple floating surfaces, it is observed that the spacing between plates has more significant effect on the wave field than their lengths. Also, the presence of relatively smaller floating plates upwave modifies remarkably the deformation and response of the downwave floating surface.
Comparison of pretherapeutic osseous tumor volume and standard hematology for prediction of hematotoxicity after PSMA-targeted radioligand therapy
Authors: Widjaja Liam , Werner Rudolf A. , Ross Tobias L. , Bengel Frank M. , Derlin Thorsten
Published: May 2021

Purpose

Hematotoxicity is a potentially dose-limiting adverse event in patients with metastasized castration-resistant prostate cancer (mCRPC) undergoing prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT). We aimed to identify clinical or PSMA-targeted imaging-derived parameters to predict hematological adverse events at early and late stages in the treatment course.

Methods

In 67 patients with mCRPC scheduled for 177Lu-PSMA-617 RLT, pretherapeutic osseous tumor volume (TV) from 68Ga-PSMA-11 PET/CT and laboratory values were assessed. We then tested the predictive capability of these parameters for early and late hematotoxicity (according to CTCAE vers. 5.0) after one cycle of RLT and in a subgroup of 32/67 (47.8%) patients after four cycles of RLT.

Results

After one cycle, 10/67 (14.9%) patients developed leukocytopenia (lymphocytopenia, 39/67 [58.2%]; thrombocytopenia, 17/67 [25.4%]). A cut-off of 5.6 × 103/mm3 for baseline leukocytes was defined by receiver operating characteristics (ROC) and separated between patients with and without leukocytopenia (P < 0.001). Baseline leukocyte count emerged as a stronger predictive factor in multivariate analysis (hazard ratio [HR], 33.94, P = 0.001) relative to osseous TV (HR, 14.24, P = 0.01). After four cycles, 4/32 (12.5%) developed leukocytopenia and the pretherapeutic leukocyte cut-off (HR, 9.97, P = 0.082) tended to predict leukocytopenia better than TV (HR, 8.37, P = 0.109). In addition, a cut-off of 1.33 × 103/mm3 for baseline lymphocytes separated between patients with and without lymphocytopenia (P < 0.001), which was corroborated in multivariate analysis (HR, 21.39, P < 0.001 vs. TV, HR, 4.57, P = 0.03). After four cycles, 19/32 (59.4%) developed lymphocytopenia and the pretherapeutic cut-off for lymphocytes (HR, 46.76, P = 0.007) also demonstrated superior predictive performance for late lymphocytopenia (TV, HR, 5.15, P = 0.167). Moreover, a cut-off of 206 × 103/mm3 for baseline platelets separated between patients with and without thrombocytopenia (P < 0.001) and also demonstrated superior predictive capability in multivariate analysis (HR, 115.02, P < 0.001 vs.TV, HR, 12.75, P = 0.025). After four cycles, 9/32 (28.1%) developed thrombocytopenia and the pretherapeutic cut-off for platelets (HR, 5.44, P = 0.048) was also superior for the occurrence of late thrombocytopenia (TV, HR, 1.44, P = 0.7).

Conclusions

Pretherapeutic leukocyte, lymphocyte, and platelet levels themselves are strong predictors for early and late hematotoxicity under PSMA-directed RLT, and are better suited than PET-based osseous TV for this purpose.
Comparative prospective randomized study of minimally invasive transpiriformis approach versus conventional posterolateral approach in total hip arthroplasty as measured by biology markers
Authors: Xiao Cong , Gao Zhixiang , Zhang Shaoyun , Long Nengji , Yao Kai , Cai Peng , He Fenglai , Liu Lijuan , Jiang Yishan
Published: May 2021

Background

Minimally invasive surgery is becoming increasingly common, but evidence of the advantages of the minimally invasive transpiriformis approach in total hip arthroplasty is limited. Therefore, our single-centre randomized controlled trial evaluated the benefits of this approach versus the posterolateral approach.

Methods

Forty-nine patients undergoing the minimally invasive transpiriformis approach and 57 patients undergoing the posterolateral approach total hip arthroplasty were analyzed. The operative time, length of hospital stay, incision length, and peri-operative data related to the surgery were recorded. In both groups, serum CRP, IL-6, HGb, Hct, MB, CK-MB, and CK levels, Harris hip scores, and VAS scores were recorded.

Results

Patients who underwent the minimally invasive transpiriformis approach had a smaller surgical incision (9.10 ± 0.94 vs. 15.56 ± 1.20 cm, P = 0.00) and shorter hospital stay (6.20 ± 1.54 vs. 12.26 ± 2.97 days, P = 0.00) than those who underwent the posterolateral approach. Serum levels of CRP, IL-6, MB, CK-MB, and CK were also lower. According to the Harris hip score, the minimally invasive transpiriformis group showed significant improvement at one week and one month after surgery.

Conclusion

Compared to the posterolateral approach, the minimally invasive transpiriformis approach for total hip arthroplasty provided rapid functional recovery, elicited a significantly reduced post-operative inflammatory response, and caused less muscle damage.
A comprehensive phenotypic characterization of a whole-body Wdr45 knock-out mouse
Authors: Biagosch Caroline A. , Vidali Silvia , Faerberboeck Michael , Hensler Svenja-Viola , Becker Lore , Amarie Oana V. , Aguilar-Pimentel Antonio , Garrett Lillian , Klein-Rodewald Tanja , Rathkolb Birgit , Zanuttigh Enrica , Calzada-Wack Julia , da Silva-Buttkus Patricia , Rozman Jan , Treise Irina , Fuchs Helmut , Gailus-Durner Valerie , de Angelis Martin Hrabě , Janik Dirk , Wurst Wolfgang , Mayr Johannes A. , Klopstock Thomas , Meitinger Thomas , Prokisch Holger , Iuso Arcangela
Published: May 2021

Pathogenic variants in the WDR45 (OMIM: 300,526) gene on chromosome Xp11 are the genetic cause of a rare neurological disorder characterized by increased iron deposition in the basal ganglia. As WDR45 encodes a beta-propeller scaffold protein with a putative role in autophagy, the disease has been named Beta-Propeller Protein-Associated Neurodegeneration (BPAN). BPAN represents one of the four most common forms of Neurodegeneration with Brain Iron Accumulation (NBIA). In the current study, we generated and characterized a whole-body Wdr45 knock-out (KO) mouse model. The model, developed using TALENs, presents a 20-bp deletion in exon 2 of Wdr45. Homozygous females and hemizygous males are viable, proving that systemic depletion of Wdr45 does not impair viability and male fertility in mice. The in-depth phenotypic characterization of the mouse model revealed neuropathology signs at four months of age, neurodegeneration progressing with ageing, hearing and visual impairment, specific haematological alterations, but no brain iron accumulation. Biochemically, Wdr45 KO mice presented with decreased complex I (CI) activity in the brain, suggesting that mitochondrial dysfunction accompanies Wdr45 deficiency. Overall, the systemic Wdr45 KO described here complements the two mouse models previously reported in the literature (PMIDs: 26,000,824, 31,204,559) and represents an additional robust model to investigate the pathophysiology of BPAN and to test therapeutic strategies for the disease.
Metastasis-directed stereotactic body radiotherapy for oligometastatic renal cell carcinoma: extent of tumor burden eradicated by radiotherapy
Authors: Liu Yang , Long Wen , Zhang Zhiling , Zhang Zitong , Mai Lixin , Huang Sijuan , Han Hui , Zhou Fangjian , Dong Pei , He Liru
Published: May 2021

Purpose

We aimed to explore whether complete eradication of tumor burden with stereotactic body radiotherapy (SBRT) would affect the outcomes of oligometastatic renal cell carcinoma (RCC).

Materials and methods

Patients diagnosed with extracranial oligometastatic RCC (no more than five metastases) between 2007 and 2019 were reviewed. Those without nephrectomy were excluded. SBRT to all, some and no lesions were defined as complete, incomplete, and no SBRT. Progression-free survival (PFS) and cancer-specific survival (CSS) were analyzed using Kaplan–Meier method, Cox regression model and the Fine and Gray method.

Result

A total of 101 patients were included, 51.5% of whom had < 3 metastases. Forty (39.6%) patients received complete SBRT, and 61 (60.4%) received no or incomplete SBRT. The 1-year LC rate was 97.3%. The complete SBRT group had significantly longer PFS (26.0 vs 18.8 months; p = 0.043) and CSS (not reached vs. 55.3 months; p = 0.012) compared with the no or incomplete SBRT group. In multivariate analysis, ECOG 0–1 (HR 0.389, 95% CI 0.167–0.906, p = 0.029) and complete SBRT were prognostic factors for CSS (HR 0.307, 95% CI 0.108–0.876, p = 0.027). Complete SBRT was associated with improved CSS in the subgroups of patients with age < 55 years, ECOG 0–1, clear-cell histology, IMDC intermediate/poor risk, metachronous metastasis, and < 3 lesions.

Conclusion

Complete eradication of tumor burden with SBRT was associated with better survival in patients with oligometastatic RCC. The recommendation of SBRT to all lesions should be individualized.
Jenseits der Klinik: Konzeptionelle Überlegungen zum Ethiktransfer in dezentralen Einrichtungen des Gesundheitswesens am Beispiel der BruderhausDiakonie Reutlingen
Authors: Burmeister Christiane , Iller Ariane , Ranisch Robert , Brand Cordula , Staib Tobias , Müller Uta
Published: May 2021

Unser Beitrag stellt ein interaktives Ethik-Konzept vor, das in Zusammenarbeit der BruderhausDiakonie Reutlingen und der Universität Tübingen entwickelt wurde, um den Eigenheiten und Bedarfen einer komplexen Organisationsstruktur gerecht zu werden, die mehrere Geschäftsfelder und Standorte unter sich vereint. Wir skizzieren die Grundzüge des interaktiven Nijmegener Modells, in dem die Kooperation eines auf Leitungsebene angesiedelten Komitees und situationsbezogener Fallbesprechungen ein fruchtbares Zusammenspiel zweier unverzichtbarer Reflexionsweisen bewirken soll („Top-Down“/„Bottom-Up“). Wir zeigen auf, welche Herausforderungen sich bei der Implementierung dieses Modells in die konkrete Aufbauorganisation der BruderhausDiakonie ergaben, und mit welchen konzeptionellen oder „implementationstechnischen“ Mitteln ihnen begegnet wurde. Im Zentrum steht dabei die Erweiterung des Nijmegener Modells um ein Verbindungselement, welches die Zusammenarbeit zwischen zentralem Ausschuss und dezentralen Fallbesprechungen koordiniert und das interaktive Moment des Modells erst ermöglicht.
Bladder metastasis without hematuria, following radiation therapy for lung adenocarcinoma
Authors: Kirisawa Takahiro , Okada Manabu , Miura Chisako , Miura Ichiro
Published: May 2021

Bladder metastasis from lung adenocarcinoma is extremely rare. Unlike primary bladder urothelial tumors, the initial symptoms of this disease vary, and include pelvic pain, dysuria, and hematuria. There are few reports on cases without microscopic hematuria. An 86-year-old woman with a previous history of radiation therapy for lung adenocarcinoma complained of urinary frequency. A urinalysis was negative for hematuria and pyuria; thus, overactive bladder was suspected. However, the patient’s symptom worsened considerably, and cystoscopy revealed bladder tumor. Transurethral resection of the bladder tumor was performed. Based on the histological, immunohistochemical examination and clinical history, the final pathological diagnosis was bladder metastasis from lung adenocarcinoma. The patient died 19 days after the operation due to severe disease progression. In this rare case, a patient with bladder metastasis from lung adenocarcinoma did not show microscopic hematuria. Cystoscopy and computed tomography helped to make a rapid and accurate diagnosis.
Control of the setting reaction and strength development of slag-blended volcanic ash-based phosphate geopolymer with the addition of boric acid
Authors: Djobo Jean Noël Yankwa , Stephan Dietmar
Published: May 2021

This work aimed to evaluate the role of the addition of blast furnace slag for the formation of reaction products and the strength development of volcanic ash-based phosphate geopolymer. Volcanic ash was replaced by 4 and 6 wt% of ground granulated blast furnace slag to accelerate the reaction kinetics. Then, the influence of boric acid for controlling the setting and kinetics reactions was also evaluated. The results demonstrated that the competition between the dissolution of boric acid and volcanic ash-slag particles is the main process controlling the setting and kinetics reaction. The addition of slag has significantly accelerated the initial and final setting times, whereas the addition of boric acid was beneficial for delaying the setting times. Consequently, it also enhanced the flowability of the paste. The compressive strength increased significantly with the addition of slag, and the optimum replaced rate was 4 wt% which resulted in 28 d strength of 27 MPa. Beyond that percentage, the strength was reduced because of the flash setting of the binder which does not allow a subsequent dissolution of the particles and their precipitation. The binders formed with the addition of slag and/or boric acid are beneficial for the improvement of the water stability of the volcanic ash-based phosphate geopolymer.
Advanced Modular Manikin and Surgical Team Experience During a Trauma Simulation: Results of a Single-Blinded Randomized Trial
Authors: Stefanidis Dimitrios , Aggarwal Rajesh , Rush Robert M. , Lee Gyusung , Blair Patrice G. , Hananel David , Park Yoon Soo , Sweet Robert M. , Wisbach Gordon G. , Sachdeva Ajit K.
Published: May 2021

BACKGROUND:

Our aim was assess whether an integrated Advanced Modular Manikin (AMM) provides improved participant experience compared with use of peripheral simulators alone during a standardized trauma team scenario. Simulation-based team training has been shown to improve team performance. To address limitations of existing manikin simulators, the AMM platform was created that enables interconnectedness, interoperability, and integration of multiple simulators (“peripherals”) into an adaptable, comprehensive training system.

METHODS:

A randomized single-blinded, crossover study with 2 conditions was used to assess learner experience differences when using the integrated AMM platform vs peripheral simulators. First responders, anesthesiologists, and surgeons rated their experience and workload with the conditions in a 3-scene standardized trauma scenario. Participant ratings were compared and focus groups conducted to obtain insight into participant experience.

RESULTS:

Fourteen teams (n = 42) participated. Team experience ratings were higher for the integrated AMM condition compared with peripherals (Cohen's d = .25, p = 0.016). Participant experience varied by background with surgeons and first responders rating their experience significantly higher compared with anesthesiologists (p < 0.001). Higher workload ratings were observed with the integrated AMM condition (Cohen's d = .35, p = 0.014) driven primarily by anesthesiologist ratings. Focus groups revealed that participants preferred the integrated AMM condition based on its increased realism, physiologic responsiveness, and feedback provided on their interventions.

CONCLUSIONS:

This first comprehensive evaluation suggests that integration with the AMM platform provides benefits over individual peripheral simulators and has the potential to expand simulation-based learning opportunities and enhance learner experience, especially for surgeons.
CONDITION (K) FOR BOOLEAN DYNAMICAL SYSTEMS
Authors: CARLSEN TOKE MEIER , KANG EUN JI
Published: May 2021

We generalize Condition (K) from directed graphs to Boolean dynamical systems and show that a locally finite Boolean dynamical system
$({{\mathcal {B}}},{{\mathcal {L}}},\theta )$
with countable
${{\mathcal {B}}}$
and
${{\mathcal {L}}}$
satisfies Condition (K) if and only if every ideal of its
$C^*$
-algebra is gauge-invariant, if and only if its
$C^*$
-algebra has the (weak) ideal property, and if and only if its
$C^*$
-algebra has topological dimension zero. As a corollary we prove that if the
$C^*$
-algebra of a locally finite Boolean dynamical system with
${{\mathcal {B}}}$
and
${{\mathcal {L}}}$
countable either has real rank zero or is purely infinite, then
$({{\mathcal {B}}}, {{\mathcal {L}}}, \theta )$
satisfies Condition (K). We also generalize the notion of maximal tails from directed graph to Boolean dynamical systems and use this to give a complete description of the primitive ideal space of the
$C^*$
-algebra of a locally finite Boolean dynamical system that satisfies Condition (K) and has countable
${{\mathcal {B}}}$
and
${{\mathcal {L}}}$
.
How Hospitals Respond to Wildfires
Authors: Thompson Elizabeth
Published: May 2021

A new study tracks intensive care unit admissions after periods of wildfire smoke pollution. A prolonged or severe smoke event has the potential to strain hospital resources.
Size‐dependent Molecular Characteristics and Possible Sources of Organic Aerosols at a Coastal New Particle Formation Hotspot of East China
Authors: Wan Yibei , Huang Xiangpeng , Ge Xinlei , Jiang Bin , Liao Yuhong , Yan Qian , Shuai Qin , Fu Qinglong , Xiao Hang , Yu Huan
Published: May 2021

We investigated size‐dependent molecular characteristics of coastal organic aerosols from <0.032 to 3.2 μm at a new particle formation (NPF) hotspot of east China by using Fourier transform‐ion cyclotron resonance mass spectrometry (FT‐ICR‐MS). Strong connection between C20–33HhOo/C18,30HhOoNn compounds in particles smaller than 0.10 μm and the volatile organic compounds emitted from local intertidal macroalgae suggests that the organic compounds (OC) in ultrafine particles are formed probably via the gas‐phase oxidation of long‐chain fatty aldehydes or acids, followed by particle‐phase accretion reactions or imine formation during the coastal NPF events. In 0.18–0.56 μm particles, dominant C8–C20 CHO, CHON, CHOS and CHONS compounds (maximum: C10 or C15) are suggested most likely to be terpene oxidation products. Highly oxygenated compounds with 0.6 ≤ H/C ≤ 1.5 and 0.67 ≤ O/C ≤ 1.2 reside mostly in 0.18–0.56 μm particles, accounting for 5% of the OC formulas in this size range. Iodinated OC are subsequently formed via electrophilic substitution of non‐iodinated OC by iodine cations (e.g., from HOI or I2) in iodine‐rich particles. CHN and Cl/Br‐containing OC account altogether for only 0.7% and 0.9% of OC formulas, respectively. As a result of the above compound distribution, the intensity weighted unsaturation degree and carbon oxidation state of OC increase with particle size. The distribution of aromatic compounds (i.e. Aromaticity Index > 0.5) is bimodal with peaks in 0.056–0.18 μm and 1.0–3.2 μm. In addition, our study observed higher unsaturation degree, carbon oxidation state and aromaticity of OC in coastal PM2.5 than inland urban PM2.5 in the same region.
The patterns of family genetic risk scores for eleven major psychiatric and substance use disorders in a Swedish national sample
Authors: Kendler Kenneth S. , Ohlsson Henrik , Sundquist Jan , Sundquist Kristina
Published: May 2021

To clarify the structure of genetic risks for 11 major psychiatric disorders, we calculated, from morbidity risks for disorders in 1st–5th degree relatives controlling for cohabitation effects, in the Swedish population born between 1932 and 1995 (n = 5,830,014), the family genetic risk scores (FGRS) for major depression (MD), anxiety disorders (AD), obsessive-compulsive disorder (OCD), bipolar disorder (BD), schizophrenia (SZ), bulimia (BUL), anorexia nervosa (AN), alcohol use disorder (AUD), drug use disorder (DUD), ADHD, and autism-spectrum disorder (ASD). For all affected individuals, we calculated their mean standardized FGRS for each disorder. The patterns of FGRS were quite similar for MD and AD, and for AUD and DUD, but substantially less similar for BUL and AN, BD and SZ, and ADHD and ASD. While OCD had high levels of FGRS for MD and AD, the overall FGRS profile differed considerably from MD and AD. ADHD FGRS scores were substantially elevated in AUD and DUD. FGRS scores for BD, OCD, AN, ASD, ADHD, and especially SZ were relatively disorder-specific while genetic risk for MD and AD had more generalized effects. The levels of FGRS for BMI, coronary artery disease, and educational attainment across our disorders replicated prior associations found using molecular genetic methods. All diagnostic categories examined had elevated FGRS for many disorders producing, for each condition, an informative FGRS profile. Using a novel method which approximates, from pedigree data, aggregate genetic risk, we have replicated and extended prior insights into the structure of genetic risk factors for key psychiatric illnesses.
A single-cell atlas of Plasmodium falciparum transmission through the mosquito
Authors: Real Eliana , Howick Virginia M. , Dahalan Farah A. , Witmer Kathrin , Cudini Juliana , Andradi-Brown Clare , Blight Joshua , Davidson Mira S. , Dogga Sunil Kumar , Reid Adam J. , Baum Jake , Lawniczak Mara K. N.
Published: May 2021

Malaria parasites have a complex life cycle featuring diverse developmental strategies, each uniquely adapted to navigate specific host environments. Here we use single-cell transcriptomics to illuminate gene usage across the transmission cycle of the most virulent agent of human malaria -Plasmodium falciparum. We reveal developmental trajectories associated with the colonization of the mosquito midgut and salivary glands and elucidate the transcriptional signatures of each transmissible stage. Additionally, we identify both conserved and non-conserved gene usage between human and rodent parasites, which point to both essential mechanisms in malaria transmission and species-specific adaptations potentially linked to host tropism. Together, the data presented here, which are made freely available via an interactive website, provide a fine-grained atlas that enables intensive investigation of theP. falciparumtranscriptional journey. As well as providing insights into gene function across the transmission cycle, the atlas opens the door for identification of drug and vaccine targets to stop malaria transmission and thereby prevent disease.
Origin of the quasi-quantized Hall effect in ZrTe5
Authors: Galeski S. , Ehmcke T. , Wawrzyńczak R. , Lozano P. M. , Cho K. , Sharma A. , Das S. , Küster F. , Sessi P. , Brando M. , Küchler R. , Markou A. , König M. , Swekis P. , Felser C. , Sassa Y. , Li Q. , Gu G. , Zimmermann M. V. , Ivashko O. , Gorbunov D. I. , Zherlitsyn S. , Förster T. , Parkin S. S. P. , Wosnitza J. , Meng T. , Gooth J.
Published: May 2021

The quantum Hall effect (QHE) is traditionally considered to be a purely two-dimensional (2D) phenomenon. Recently, however, a three-dimensional (3D) version of the QHE was reported in the Dirac semimetal ZrTe5. It was proposed to arise from a magnetic-field-driven Fermi surface instability, transforming the original 3D electron system into a stack of 2D sheets. Here, we report thermodynamic, spectroscopic, thermoelectric and charge transport measurements on such ZrTe5 samples. The measured properties: magnetization, ultrasound propagation, scanning tunneling spectroscopy, and Raman spectroscopy, show no signatures of a Fermi surface instability, consistent with in-field single crystal X-ray diffraction. Instead, a direct comparison of the experimental data with linear response calculations based on an effective 3D Dirac Hamiltonian suggests that the quasi-quantization of the observed Hall response emerges from the interplay of the intrinsic properties of the ZrTe5 electronic structure and its Dirac-type semi-metallic character.
Full gaze contingency provides better reading performance than head steering alone in a simulation of prosthetic vision
Authors: Paraskevoudi Nadia , Pezaris John S.
Published: May 2021

The visual pathway is retinotopically organized and sensitive to gaze position, leading us to hypothesize that subjects using visual prostheses incorporating eye position would perform better on perceptual tasks than with devices that are merely head-steered. We had sighted subjects read sentences from the MNREAD corpus through a simulation of artificial vision under conditions of full gaze compensation, and head-steered viewing. With 2000 simulated phosphenes, subjects (n = 23) were immediately able to read under full gaze compensation and were assessed at an equivalent visual acuity of 1.0 logMAR, but were nearly unable to perform the task under head-steered viewing. At the largest font size tested, 1.4 logMAR, subjects read at 59 WPM (50% of normal speed) with 100% accuracy under the full-gaze condition, but at 0.7 WPM (under 1% of normal) with below 15% accuracy under head-steering. We conclude that gaze-compensated prostheses are likely to produce considerably better patient outcomes than those not incorporating eye movements.
Knock-in and precise nucleotide substitution using near-PAMless engineered Cas9 variants in Dictyostelium discoideum
Authors: Asano Yuu , Yamashita Kensuke , Hasegawa Aoi , Ogasawara Takanori , Iriki Hoshie , Muramoto Tetsuya
Published: May 2021

The powerful genome editing tool Streptococcus pyogenes Cas9 (SpCas9) requires the trinucleotide NGG as a protospacer adjacent motif (PAM). The PAM requirement is limitation for precise genome editing such as single amino-acid substitutions and knock-ins at specific genomic loci since it occurs in narrow editing window. Recently, SpCas9 variants (i.e., xCas9 3.7, SpCas9-NG, and SpRY) were developed that recognise the NG dinucleotide or almost any other PAM sequences in human cell lines. In this study, we evaluated these variants in Dictyostelium discoideum. In the context of targeted mutagenesis at an NG PAM site, we found that SpCas9-NG and SpRY were more efficient than xCas9 3.7. In the context of NA, NT, NG, and NC PAM sites, the editing efficiency of SpRY was approximately 60% at NR (R = A and G) but less than 22% at NY (Y = T and C). We successfully used SpRY to generate knock-ins at specific gene loci using donor DNA flanked by 60 bp homology arms. In addition, we achieved point mutations with efficiencies as high as 97.7%. This work provides tools that will significantly expand the gene loci that can be targeted for knock-out, knock-in, and precise point mutation in D. discoideum.
Transcript levels of spindle and kinetochore-associated complex 1/3 as prognostic biomarkers correlated with immune infiltrates in hepatocellular carcinoma
Authors: Yu De-Chen , Chen Xiang-Yi , Li Xin , Zhou Hai-Yu , Yu De-Quan , Yu Xiao-Lei , Hu Yi-Cun , Zhang Rui-Hao , Zhang Xiao-Bo , Zhang Kun , An Jiang-Dong
Published: May 2021

The spindle and kinetochore-associated protein complex (Ska) is an essential component in chromosome segregation. It comprises three proteins (Ska1, Ska2, and Ska3) with theorized roles in chromosomal instability and tumor development, and its overexpression has been widely reported in a variety of tumors. However, the prognostic significance and immune infiltration of Ska proteins in hepatocellular carcinoma (HCC) are not completely understood. The bioinformatics tools Oncomine, UALCAN, gene expression profiling interactive analysis 2 (GEPIA2), cBioPortal, GeneMANIA, Metascape, and TIMER were used to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of the Ska protein complex in HCC patients. We found that the mRNA expression of the Ska complex was markedly upregulated in HCC. High expression of the Ska complex is closely correlated with tumor stage, patient race, tumor grade, and TP53 mutation status. In addition, high expression of the Ska complex was significantly correlated with poor disease-free survival, while the high expression levels of Ska1 and Ska3 were associated with shorter overall survival. The biological functions of the Ska complex in HCC primarily involve the amplification of signals from kinetochores, the mitotic spindle, and (via a MAD2 invasive signal) unattached kinetochores. Furthermore, the expression of the complex was positively correlated with tumor-infiltrating cells. These results may provide new insights into the development of immunotherapeutic targets and prognostic biomarkers for HCC.
Minor allele of rs55763075 located in MTHFR is associated with the risk of cognitive impairment after anesthesia via modulating miR-34b
Authors: Li Si-ying , Lei He-shou , Wu Xiao-yun , Li Kai , Liu Zhi-min , Lu Jian-hui , Chen Xiao-yun
Published: May 2021

This study aimed to investigate the association between cognitive impairment after general anesthesia and rs55763075 polymorphisms. We enrolled and grouped patients undergoing general anesthesia according to their genotypes of rs55763075 polymorphism. Mini–Mental State Examination (MMSE) scoring was performed to evaluate the cognitive status of patients. Quantitative real-time PCR was carried out to analyze the expression of methylenetetrahydrofolate reductase (MTHFR) mRNA and miR-34b while Western blot was performed to evaluate the expression of MTHFR protein. Furthermore, we studied the effect of rs55763075 polymorphism on the expression of MEHFR via luciferase assay. Accordingly, we found that the MMSE score in GG/GA groups was significantly higher than that in AA group. And a significant reduction of MTHFR mRNA expression was observed in the serum and peripheral blood mononuclear cells (PBMCs) of patients carrying AA genotype compared with the patients carrying GG/GA genotypes. Moreover, the MTHFR expression was much lower in the cultured AA-genotyped cells transfected with miR-34b. Luciferase assay results also showed that miR-34b transfection reduced luciferase activity in the cells carrying A allele but not in cells carrying G allele. In summary, the data of this study showed that minor allele (A) of rs55763075 polymorphisms in the 3'-untranslated region of MTHFR mRNA generated a potential binding site for miR-34b, which led to reduced level of folic acid in the patients carrying the AA genotype. Furthermore, we found that the MMSE score of AA-genotyped patients was lower than that of patients carrying GG/GA genotypes.
The impact of hypothetical interventions on adiposity in adolescence
Authors: Gebremariam Mekdes K. , Nianogo Roch A. , Lien Nanna , Bjelland Mona , Klepp Knut-Inge , Bergh Ingunn H. , Ommundsen Yngvar , Arah Onyebuchi A.
Published: May 2021

In order to develop effective public health initiatives aimed at promoting healthy weight development, identifying the interventions/combination of interventions with the highest beneficial effect on body weight is vital. The study aimed to estimate the mean BMI at age 13 under hypothetical interventions targeting dietary behavior, physical activity and screen time at age 11. We used data from a school-based cohort study of 530 participants followed between the ages of 11 and 13. We used g-computation, a causal modeling method, to estimate the impact of single and combined hypothetical behavioral interventions at age 11 on BMI at age 13. Of the hypothetical interventions, the one with the largest population mean difference in BMI was the one combining all interventions (dietary behavior, physical activity and screen time interventions) and assuming 100% intervention adherence, with a population mean differences of − 0.28 (95% CI − 0.59, 0.07). Isolated behavioral interventions had a limited impact on BMI. This study demonstrated that a combination of healthy dietary behavior and physical activity promotion, as well as screen time reduction interventions at age 11 could have the highest beneficial effect on the reduction of BMI at age 13, although the change in BMI was small. The findings highlight the importance of a systems approach to obesity prevention focusing on multicomponent interventions.
Supervised binary classification methods for strawberry ripeness discrimination from bioimpedance data
Authors: Ibba Pietro , Tronstad Christian , Moscetti Roberto , Mimmo Tanja , Cantarella Giuseppe , Petti Luisa , Martinsen Ørjan G. , Cesco Stefano , Lugli Paolo
Published: May 2021

Strawberry is one of the most popular fruits in the market. To meet the demanding consumer and market quality standards, there is a strong need for an on-site, accurate and reliable grading system during the whole harvesting process. In this work, a total of 923 strawberry fruit were measured directly on-plant at different ripening stages by means of bioimpedance data, collected at frequencies between 20 Hz and 300 kHz. The fruit batch was then splitted in 2 classes (i.e. ripe and unripe) based on surface color data. Starting from these data, six of the most commonly used supervised machine learning classification techniques, i.e. Logistic Regression (LR), Binary Decision Trees (DT), Naive Bayes Classifiers (NBC), K-Nearest Neighbors (KNN), Support Vector Machine (SVM) and Multi-Layer Perceptron Networks (MLP), were employed, optimized, tested and compared in view of their performance in predicting the strawberry fruit ripening stage. Such models were trained to develop a complete feature selection and optimization pipeline, not yet available for bioimpedance data analysis of fruit. The classification results highlighted that, among all the tested methods, MLP networks had the best performances on the test set, with 0.72, 0.82 and 0.73 for the F$$_1$$

1

, F$$_{0.5}$$

0.5

and F$$_2$$

2

-score, respectively, and improved the training results, showing good generalization capability, adapting well to new, previously unseen data. Consequently, the MLP models, trained with bioimpedance data, are a promising alternative for real-time estimation of strawberry ripeness directly on-field, which could be a potential application technique for evaluating the harvesting time management for farmers and producers.
Auxiliary rapid identification of pathogenic and antagonistic microorganisms associated with Coptis chinensis root rot by high-throughput sequencing
Authors: Liao Hailang , Huang Ling , Li Na , Ke Wenjia , Xiang Yiqing , Ma Yuntong
Published: May 2021

Root rot reduces the yield and medical quality of C. chinensis (Cc). Previous studies of Coptis root rot focused on the identification of pathogens and the rhizosphere microbial community composition. The present study aimed to identify potential pathogenic and antagonistic microorganisms associated with root rot based on a high-throughput sequencing technique to prevent this disease. Healthy and diseased Cc in the endosphere and rhizosphere from the same field were collected to investigate the differences in microbiome composition and function. The results showed that the composition and function of microbes were different. The numbers of animal pathogens, soil saprotrophs, plant saprotrophs, and wood saprotrophs in the endosphere of diseased Cc were higher than those in the healthy endosphere and were dominated by Phaeosphaeriaceae, Cladorrhinum, Fusarium, Exophiala, and Melanommataceae. Fusarium, Volutella, Cladorrhinum, Cylindrocarpon, and Exophiala were significantly enriched in the endosphere of the diseased plants. Co-occurrence network analysis showed that Bacillus was negatively correlated with Fusarium, Volutella, and Cylindrocarpon, indicating that Bacillus may be antagonistic microorganisms. To verify the sequencing results, F. solani and F. avenaceum were isolated and verified as pathogens, and 14 Bacillus strains were isolated, which displayed an apparent suppression effect against the two pathogens on PDA medium and detached roots. The strategy of high-throughput sequencing has the potential for the comprehensive identification of pathogenic and antagonistic microorganisms for plant disease. These results provide research ideas and microbial resources for future studies on mitigating or preventing root rot damage to Cc.
Identification of BHLHE40 expression in peripheral blood mononuclear cells as a novel biomarker for diagnosis and prognosis of hepatocellular carcinoma
Authors: Kunadirek Pattapon , Ariyachet Chaiyaboot , Sriphoosanaphan Supachaya , Pinjaroen Nutcha , Sirichindakul Pongserath , Nookaew Intawat , Chuaypen Natthaya , Tangkijvanich Pisit
Published: May 2021

Novel and sensitive biomarkers is highly required for early detection and predicting prognosis of hepatocellular carcinoma (HCC). Here, we investigated transcription profiles from peripheral blood mononuclear cells (PBMCs) of 8 patients with HCC and PBMCs from co-culture model with HCC using RNA-Sequencing. These transcription profiles were cross compared with published microarray datasets of PBMCs in HCC to identify differentially expressed genes (DEGs). A total of commonly identified of 24 DEGs among these data were proposed as cancer-induced genes in PBMCs, including 18 upregulated and 6 downregulated DEGs. The KEGG pathway showed that these enriched genes were mainly associated with immune responses. Five up-regulated candidate genes including BHLHE40, AREG, SOCS1, CCL5, and DDIT4 were selected and further validated in PBMCs of 100 patients with HBV-related HCC, 100 patients with chronic HBV infection and 100 healthy controls. Based on ROC analysis, BHLHE40 and DDIT4 displayed better diagnostic performance than alpha-fetoprotein (AFP) in discriminating HCC from controls. Additionally, BHLHE40 and DDIT4 had high sensitivity for detecting AFP-negative and early-stage HCC. BHLHE40 was also emerged as an independent prognostic factor of overall survival of HCC. Together, our study indicated that BHLHE40 in PBMCs could be a promising diagnostic and prognostic biomarker for HBV-related HCC.
Positive selection and intrinsic disorder are associated with multifunctional C4(AC4) proteins and geminivirus diversification
Authors: Deom Carl Michael , Brewer Marin Talbot , Severns Paul M.
Published: May 2021

Viruses within the Geminiviridae family cause extensive agricultural losses. Members of four genera of geminiviruses contain a C4 gene (AC4 in geminiviruses with bipartite genomes). C4(AC4) genes are entirely overprinted on the C1(AC1) genes, which encode the replication-associated proteins. The C4(AC4) proteins exhibit diverse functions that may be important for geminivirus diversification. In this study, the influence of natural selection on the evolutionary diversity of 211 C4(AC4) genes relative to the C1(AC1) sequences they overlap was determined from isolates of the Begomovirus and Curtovirus genera. The ratio of nonsynonymous (dN) to synonymous (dS) nucleotide substitutions indicated that C4(AC4) genes are under positive selection, while the overlapped C1(AC1) sequences are under purifying selection. Ninety-one of 200 Begomovirus C4(AC4) genes encode elongated proteins with the extended regions being under neutral selection. C4(AC4) genes from begomoviruses isolated from tomato from native versus exotic regions were under similar levels of positive selection. Analysis of protein structure suggests that C4(AC4) proteins are entirely intrinsically disordered. Our data suggest that non-synonymous mutations and mutations that increase the length of C4(AC4) drive protein diversity that is intrinsically disordered, which could explain C4/AC4 functional variation and contribute to both geminivirus diversification and host jumping.
A novel system for intensive Diadema antillarum propagation as a step towards population enhancement
Authors: Pilnick Aaron R. , O’Neil Keri L. , Moe Martin , Patterson Joshua T.
Published: May 2021

The long-spined sea urchin Diadema antillarum was once an abundant reef grazing herbivore throughout the Caribbean. During the early 1980s, D. antillarum populations were reduced by > 93% due to an undescribed disease. This event resulted in a lack of functional reef herbivory and contributed to ongoing ecological shifts from hard coral towards macroalgae dominated reefs. Limited natural recovery has increased interest in a range of strategies for augmenting herbivory. An area of focus has been developing scalable ex situ methods for rearing D. antillarum from gametes. The ultimate use of such a tool would be exploring hatchery origin restocking strategies. Intensive ex situ aquaculture is a potentially viable, yet difficult, method for producing D. antillarum at scales necessary to facilitate restocking. Here we describe a purpose-built, novel recirculating aquaculture system and the broodstock management and larval culture process that has produced multiple D. antillarum cohorts, and which has the potential for practical application in a dedicated hatchery setting. Adult animals held in captivity can be induced to spawn year-round, with some evidence for annual and lunar periodicity. Fecundity and fertilization rates are both consistently very high, yet challenges persist in both late stage larval development and early post-settlement survival. Initial success was realized with production of 100 juvenile D. antillarum from ~ 1200 competent larvae. While the system we describe requires a significant level of investment and technical expertise, this work advances D. antillarum culture efforts in potential future hatchery settings and improves the viability of scalable ex situ production for population enhancement.
Gene expression alterations in salivary gland epithelia of Sjögren’s syndrome patients are associated with clinical and histopathological manifestations
Authors: Dela Cruz Ariana , Kartha Vinay , Tilston-Lunel Andrew , Mi Rongjuan , Reynolds Taylor L. , Mingueneau Michael , Monti Stefano , Jensen Janicke L. , Skarstein Kathrine , Varelas Xaralabos , Kukuruzinska Maria A.
Published: May 2021

Sjögren’s syndrome (SS) is a complex autoimmune disease associated with lymphocytic infiltration and secretory dysfunction of salivary and lacrimal glands. Although the etiology of SS remains unclear, evidence suggests that epithelial damage of the glands elicits immune and fibrotic responses in SS. To define molecular changes underlying epithelial tissue damage in SS, we laser capture microdissected (LCM) labial salivary gland epithelia from 8 SS and 8 non-SS controls for analysis by RNA sequencing (RNAseq). Computational interrogation of gene expression signatures revealed that, in addition to a division of SS and non-SS samples, there was a potential intermediate state overlapping clustering of SS and non-SS samples. Differential expression analysis uncovered signaling events likely associated with distinct SS pathogenesis. Notable signals included the enrichment of IFN-γ and JAK/STAT-regulated genes, and the induction of genes encoding secreted factors, such as LTF, BMP3, and MMP7, implicated in immune responses, matrix remodeling and tissue destruction. Identification of gene expression signatures of salivary epithelia associated with mixed clinical and histopathological characteristics suggests that SS pathology may be defined by distinct molecular subtypes. We conclude that gene expression changes arising in the damaged salivary epithelia may offer novel insights into the signals contributing to SS development and progression.
Muscle metabolome and adipose tissue mRNA expression of lipid metabolism-related genes in over-conditioned dairy cows differing in serum-metabotype
Authors: Sadri Hassan , Ghaffari Morteza Hosseini , Schuh Katharina , Koch Christian , Sauerwein Helga
Published: May 2021

Over-conditioned dairy cows, classified by body condition score (BCS) and backfat thickness (BFT) are less able to metabolically adapt to the rapidly increasing milk yield after parturition. Based on serum metabolome and cluster analyses, high BCS cows (HBCS) could be classified into metabotypes that are more similar to normal (NBCS) cows, i.e., HBCS predicted normal (HBCS-PN) than the HBCS predicted high (HBCS-PH) cows—similar to the concept of obese but metabolically healthy humans. Our objective was to compare muscle metabolome and mRNA abundance of genes related to lipogenesis and lipolysis in adipose tissue between HBCS-PH (n = 13), HBCS-PN (n = 6), and NBCS-PN (n = 15). Tail-head subcutaneous fat was biopsied on d −49, 3, 21, and 84 relative to parturition. Potential differences in the oxidative capacity of skeletal muscle were assessed by targeted metabolomics in M. semitendinosus from d 21. Besides characteristic changes with time, differences in the mRNA abundance were limited to lipogenesis-related genes on d −49 (HBCS-PH > HBCS-PN). The HBCS-PH had more than two-fold higher muscle concentrations of short (C2, C4-OH, C6-OH) and long-chain acylcarnitines (C16, C18, and C18:1) than HBCS-PN, indicating a greater oxidative capacity for fatty acids (and utilization of ketones) in muscle of HBCS-PN than HBCS-PH cows.