bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-dimensional direct numerical simulation of flow induced by an oscillating sphere close to a plane boundary
Authors: Satish Samayam , Leontini Justin S. , Manasseh Richard , Sannasiraj S. A. , Sundar V.
Published: September 2021

The dynamic interaction of submerged spherical structures with ocean waves alters the local flow field and is responsible for the movement of sediments over the seabed, which would have detrimental effects on the ecosystems. The present research aims to gain insight into the effect of a plane boundary on the vorticity dynamics and shear modifications on the plane boundary induced by the flow due to an oscillating sphere. The flow field around an oscillating sphere close to a plane boundary is investigated numerically by three-dimensional direct numerical simulation of the Navier–Stokes equations. The sphere oscillates perpendicular to the plane boundary modeling the seabed. The flow structure, resulting mean and fluctuating shear stress distribution on the plane boundary, and the Lagrangian particle transport are investigated as a function of the sphere oscillation amplitude, Reynolds number, and the distance of the sphere from the plane boundary. The systematic correlations for the variation of maximum shear stress on the plane boundary are estimated from scaling parameters. The time-mean results are then linked to the Lagrangian particle transport where it is observed that the Lagrangian path lines track the mean streamlines closely. Further, the particles at the stagnation zone cease drifting and oscillate about a constant mean position. The practical significance of this result is that a ring of zero mean shear on the seabed is found toward where particles congregate. This provides a guide for the optimum location for the mooring anchors, minimizing the risk of anchor scour or undermining.
Haplotype divergence supports long-term asexuality in the oribatid miteOppiella nova
Authors: Brandt Alexander , Tran Van Patrick , Bluhm Christian , Anselmetti Yoann , Dumas Zoé , Figuet Emeric , François Clémentine M. , Galtier Nicolas , Heimburger Bastian , Jaron Kamil S. , Labédan Marjorie , Maraun Mark , Parker Darren J. , Robinson-Rechavi Marc , Schaefer Ina , Simion Paul , Scheu Stefan , Schwander Tanja , Bast Jens
Published: September 2021

Significance

Putatively ancient asexual species pose a challenge to theory because they appear to escape the predicted negative long-term consequences of asexuality. Although long-term asexuality is difficult to demonstrate, specific signatures of haplotype divergence, called the “Meselson effect,” are regarded as strong support for long-term asexuality. Here, we provide evidence for the Meselson effect in an asexual oribatid mite species,Oppiella nova, and we show that the effect is not caused by hybridization or polyploidization. Our findings provide conclusive evidence for the long-term absence of sex inO. novaand suggest that asexual oribatid mites can escape the dead-end fate usually associated with asexual reproduction.
Integrated farming with intercropping increases food production while reducing environmental footprint
Authors: Chai Qiang , Nemecek Thomas , Liang Chang , Zhao Cai , Yu Aizhong , Coulter Jeffrey A. , Wang Yifan , Hu Falong , Wang Li , Siddique Kadambot H. M. , Gan Yantai
Published: September 2021

Significance

The world has been struggling to find sustainable ways to increase crop production to satisfy the needs for food, feed, fiber, and industrial uses while reducing negative environmental impacts. This challenge is magnified in countries/regions where the availability of farmable land for agriculture is limited. We developed an integrated cropping system that incorporates key farming tactics. Tested in 16 field experiments over 12 consecutive years (2006 to 2017), the integrated system increased crop yields while decreasing the environmental footprint. The integration enables significant synergies in biophysical processes to occur under a wide range of crop inputs, suggesting that system integration can be adopted globally for a range of smallholder farming.
The binding of the small heat-shock protein αB-crystallin to fibrils of α-synuclein is driven by entropic forces
Authors: Scheidt Tom , Carozza Jacqueline A. , Kolbe Carl C. , Aprile Francesco A. , Tkachenko Olga , Bellaiche Mathias M. J. , Meisl Georg , Peter Quentin A. E. , Herling Therese W. , Ness Samuel , Castellana-Cruz Marta , Benesch Justin L. P. , Vendruscolo Michele , Dobson Christopher M. , Arosio Paolo , Knowles Tuomas P. J.
Published: September 2021

Significance

The formation of amyloid fibrils and toxic oligomeric species has been shown to be inhibited by their interactions with molecular chaperones, thus modulating monomer sequestration and toxicity in the context of neurodegenerative diseases. Understanding the physical and chemical properties underlying chaperone binding processes is essential to explore new therapeutic strategies to target toxic amyloid species. Here, we determine that the binding of the small heat-shock protein

α

B-crystallin to

α

-synculein fibrils, a protein which is related to the progression of Parkinson’s disease, is driven by entropic forces. By applying a microfluidic platform, we accurately quantified the thermodynamics and the kinetics of this intermolecular interaction in the condensed phase and hypothesize that

α

B-crystallin oligomers work as an entropic buffer system.
Machine learning potentials for complex aqueous systems made simple
Authors: Schran Christoph , Thiemann Fabian L. , Rowe Patrick , Müller Erich A. , Marsalek Ondrej , Michaelides Angelos
Published: September 2021

Significance

Understanding complex materials, in particular those with solid–liquid interfaces, such as water on surfaces or under confinement, is a key challenge for technological and scientific progress. Although established simulation approaches have been able to provide important atomistic insight, ab initio techniques struggle with the required time and length scales, while force field methods can often be limited in terms of their accuracy. Here we show how these limitations can be overcome in a simple and automated machine learning procedure to provide accurate models of interactions at the ab initio level, as illustrated for a variety of complex aqueous systems. These developments open up the prospect of the straightforward exploration of many technologically relevant systems by molecular simulations.
Robust, self-adhesive, reinforced polymeric nanofilms enabling gas-permeable dry electrodes for long-term application
Authors: Wang Yan , Lee Sunghoon , Wang Haoyang , Jiang Zhi , Jimbo Yasutoshi , Wang Chunya , Wang Binghao , Kim Jae Joon , Koizumi Mari , Yokota Tomoyuki , Someya Takao
Published: September 2021

Significance

We have succeeded in fabricating a highly robust, adhesive, gas-permeable free-standing polymeric nanofilm with a thickness of less than 100 nm. A gas-permeable dry electrode comprising of a nanofilm and an Au layer can adhere to the human skin by van der Waals forces alone for 1 wk for high-fidelity electrocardiogram recording. Our method has overcome the major bottleneck in continuously monitoring biosignals for a long period of time with high precision under daily life conditions, opening up new opportunities in a wide range of applications in fields such as medicine, healthcare, sports, fitness, virtual reality, and entertainment.
The variance of the CMB temperature gradient: a new signature of a multiply connected Universe
Authors: Aurich Ralf , Buchert Thomas , France Martin J , Steiner Frank
Published: September 2021

In this work we investigate the standard deviation of the cosmic microwave background (CMB) temperature gradient field as a signature for a multiply connected nature of the Universe. CMB simulations of a spatially infinite Universe model within the paradigm of the standard cosmological model present non-zero two-point correlations at any angular scale. This is in contradiction with the extreme suppression of correlations at scales above 60° in the observed CMB maps. Universe models with spatially multiply connected topology contain typically a discrete spectrum of the Laplacian with a specific wave-length cut-off and thus lead to a suppression of the correlations at large angular scales, as observed in the CMB (in general there can be also an additional continuous spectrum). Among the simplest examples are three-dimensional tori which possess only a discrete spectrum. To date, the Universe models with non-trivial topology such as the toroidal space are the only models that possess a two-point correlation function showing a similar behaviour as the one derived from the observed Planck CMB maps. In this work it is shown that the normalized standard deviation of the CMB temperature gradient field does hierarchically detect the change in size of the cubic three-torus, if the volume of the Universe is smaller than ≃2.5 × 103 Gpc3. It is also shown that the variance of the temperature gradient of the Planck maps is consistent with the median value of simulations within the standard cosmological model. All flat tori are globally homogeneous, but are globally anisotropic. However, this study also presents a test showing a level of homogeneity and isotropy of all the CMB map ensembles for the different torus sizes considered that are nearly at the same weak level of anisotropy revealed by the CMB in the standard cosmological model.
Estimating confidence intervals for cerebral autoregulation: a parametric bootstrap approach
Authors: Bryant Jack E D , Birch Anthony A , Panerai Ronney B , Nikolic Dragana , Bulters Diederik , Simpson David M
Published: September 2021

Cerebral autoregulation (CA) refers to the ability of the brain vasculature to control blood flow in the face of changing blood pressure. One of the methods commonly used to assess cerebral autoregulation, especially in participants at rest, is the analysis of phase derived from transfer function analysis (TFA), relating arterial blood pressure (ABP) to cerebral blood flow (CBF). This and other indexes of CA can provide consistent results when comparing groups of subjects (e.g. patients and healthy controls or normocapnia and hypercapnia) but can be quite variable within and between individuals. The objective of this paper is to present a novel parametric bootstrap method, used to estimate the sampling distribution and hence confidence intervals (CIs) of the mean phase estimate in the low-frequency band, in order to optimise estimation of measures of CA function and allow more robust inferences on the status of CA from individual recordings. A set of simulations was used to verify the proposed method under controlled conditions. In 20 healthy adult volunteers (age 25.53.5 years), ABP and CBF velocity (CBFV) were measured at rest, using a Finometer device and Transcranial Doppler (applied to the middle cerebral artery), respectively. For each volunteer, five individual recordings were taken on different days, each approximately 18 min long. Phase was estimated using TFA. Analysis of recorded data showed widely changing CIs over the duration of recordings, which could be reduced when noisy data and frequencies with low coherence were excluded from the analysis (Wilcoxon signed rank test p = 0.0065). The TFA window-lengths of 50s gave smaller CIs than lengths of 100s (p < 0.001) or 20s (p < 0.001), challenging the usual recommendation of 100s. The method adds a much needed flexible statistical tool for CA analysis in individual recordings.
Germicidal ultraviolet LEDs: a review of applications and semiconductor technologies
Authors: Zollner Christian J , DenBaars S P , Speck J S , Nakamura S
Published: September 2021

Ultraviolet light emitting diodes (UV LEDs) are one of the most promising technologies for preventing future pandemics, improving health outcomes, and disinfecting water sources. Currently available UV LEDs emitting in the conventional germicidal wavelength range (254–285 nm) have efficiencies below 5% and cost about 100 times more (per watt) than mercury vapor lamps. On the other hand, germicidal UV LEDs provide many advantages over vapor lamps including instant-on and dimmable functionality, wavelength tunability, miniaturization, and durability, and are already in widespread use for certain applications. It is expected that III-nitride based UV LEDs will soon have similar cost and efficiency to white LEDs and will become the dominant germicidal light source within this decade. Unlike vapor discharge lamps, LEDs have theoretical efficiency limits approaching 100%; the challenges to improving UV LED efficiency are not fundamental, but technological. Improvements in material quality, chemical purity, electrical conductivity, optical transparency, and fabrication technologies are needed. In this review, we outline the major challenges in each of these areas and summarize the recent advances that have enabled rapid improvements in UV LED efficiency within the past 5 years. We discuss the physical principles underlying the mechanisms of improved efficiency, and comment on likely future trends in UV LED design and commercialization.
Conduction and stability performance of CsH2PO4 with NaH2PO4/ZrO2 for fuel cell
Authors: Veer Dharm , Kumar Pawan , Singh Deshraj , Kumar Devendra , Katiyar Ram S
Published: September 2021

Solid acid composites of CsH2PO4/NaH2PO4/ZrO2 with different weight ratios of CsH2PO4 (CDP), NaH2PO4 (SDP), and ZrO2 were synthesized and characterized. The characterizations of the solid acid composite were carried out for determining structure, thermal stability, and conductivity, utilizing x-ray Diffraction, Fourier Transform Infrared Spectroscopy, Thermogravimetric analysis, Differential Thermal Analysis, and conductivity measurements. The composite powders were in the form of pellets of 4 mm thickness for conductivity measurement. SDP in the composites has a large effect on the conductivity measurement and this material increased the low-temperature conductivity of CDP by up to 1.5 orders of magnitude. The superprotonic transition was identified at temperatures from 220 to 270 °C in CDP/SDP/ZrO2 composites under atmospheric pressure. The thermal stability of the solid acid composites for dehydration, melting, and decomposition was investigated in the temperature range of 50 to 300 °C under environments with atmospheric humidification.
Nationwide Prevalence and Genotype Distribution of High-Risk Human Papillomavirus Infection in China
Authors: Zeng Zhengyu , Austin R Marshall , Wang Lin , Guo Xiaolei , Zeng Qiuqiong , Zheng Baowen , Zhao Chengquan
Published: September 2021

Objectives

Extended high-risk human papillomavirus (hrHPV) genotype testing has recently been introduced in routine cervical cancer screening. Changes in national and regional hrHPV genotype prevalence offer an objective baseline indicator of the future impact of mass HPV vaccination and HPV-based cervical screening.

Methods

This retrospective study reports nationwide hrHPV genotyping results from July 2018 to June 2019 in 29 KingMed Diagnostics laboratories throughout China.

Results

In total, 2,458,227 hrHPV genotyping results were documented from KingMed’s nationwide laboratory database during the study period. The overall prevalence of hrHPV-positive results was 19.1%, with twin peaks for highest hrHPV infection rates in women younger than 30 years of age (22.0%) and 50 years of age and older (21.8%). The most frequently detected hrHPV genotypes were HPV-52 (4.7%), HPV-16 (3.4%), HPV-53 (2.5%), HPV-58 (2.4%), HPV-51 (2.0%), and HPV-68 (1.6%). Overall, hrHPV-positive results varied regionally from 15.3% to 24.4%.

Conclusions

Nationwide hrHPV genotyping results from KingMed laboratories offer a baseline for measuring the future impact of large-scale HPV vaccination. High hrHPV infection rates in older (≥50 years) Chinese women likely reflect the limited extent of cervical screening in China. High rates of hrHPV infection and variable regional hrHPV genotype distribution may represent limiting factors for cost-effective implementation of hrHPV-based cervical screening in China.
An evolutionary model of sensitive periods when the reliability of cues varies across ontogeny
Authors: Walasek Nicole , Frankenhuis Willem E , Panchanathan Karthik
Published: September 2021

Sensitive periods are widespread in nature, but their evolution is not well understood. Recent mathematical modeling has illuminated the conditions favoring the evolution of sensitive periods early in ontogeny. However, sensitive periods also exist at later stages of ontogeny, such as adolescence. Here, we present a mathematical model that explores the conditions that favor sensitive periods at later developmental stages. In our model, organisms use environmental cues to incrementally construct a phenotype that matches their environment. Unlike in previous models, the reliability of cues varies across ontogeny. We use stochastic dynamic programming to compute optimal policies for a range of evolutionary ecologies and then simulate developmental trajectories to obtain mature phenotypes. We measure changes in plasticity across ontogeny using study paradigms inspired by empirical research: adoption and cross-fostering. Our results show that sensitive periods only evolve later in ontogeny if the reliability of cues increases across ontogeny. The onset, duration, and offset of sensitive periods—and the magnitude of plasticity—depend on the specific parameter settings. If the reliability of cues decreases across ontogeny, sensitive periods are favored only early in ontogeny. These results are robust across different paradigms suggesting that empirical findings might be comparable despite different experimental designs.
Approaches to oocyte meiotic arrest in vitro and impact on oocyte developmental competence
Authors: Richani Dulama , Gilchrist Robert B
Published: September 2021

Oocytes are maintained in a state of meiotic arrest following the first meiotic division until ovulation is triggered. Within the antral follicle, meiotic arrest is actively suppressed in a process facilitated by the cyclic nucleotides cGMP and cAMP. If removed from this inhibitory follicular environment and cultured in vitro, mammalian oocytes undergo spontaneous meiotic resumption in the absence of the usual stimulatory follicular stimuli, leading to asynchronicity with oocyte cytoplasmic maturation and lower developmental competence. For more than 50 years, pharmacological agents have been used to attenuate oocyte germinal vesicle (GV) breakdown in vitro. Agents that increase intra-oocyte cAMP or prevent its degradation have been predominantly used; however, agents such as kinase and protein synthesis inhibitors have also been trialed. Twenty years of research demonstrates that maintaining GV arrest for a period before in vitro maturation (IVM) improves oocyte developmental competence, and is likely attributed to maintenance of bidirectional communication with cumulus cells leading to improved oocyte metabolic function. However, outcomes are influenced by various factors including the mode of action of the modulators, dose, treatment duration, species, and the degree of hormonal priming of the oocyte donor. Cyclic GMP and/or cAMP modulation in a prematuration step (called pre-IVM) prior to IVM has shown the greatest consistency in improving oocyte developmental competence, whereas kinase and protein synthesis inhibitors have proven less effective at improving IVM outcomes. Such pre-IVM approaches have shown potential to alter current use of artificial reproductive technologies in medical and veterinary practice.
Cerebrospinal fluid is a significant fluid source for anoxic cerebral oedema
Authors: Du Ting , Mestre Humberto , Kress Benjamin T , Liu Guojun , Sweeney Amanda M , Samson Andrew J , Rasmussen Martin Kaag , Mortensen Kristian Nygaard , Bork Peter A R , Peng Weiguo , Olveda Genaro E , Bashford Logan , Toro Edna R , Tithof Jeffrey , Kelley Douglas H , Thomas John H , Hjorth Poul G , Martens Erik A , Mehta Rupal I , Hirase Hajime , Mori Yuki , Nedergaard Maiken
Published: September 2021

Cerebral oedema develops after anoxic brain injury. In two models of asphyxial and asystolic cardiac arrest without resuscitation, we found that oedema develops shortly after anoxia secondary to terminal depolarizations and the abnormal entry of CSF. Oedema severity correlated with the availability of CSF with the age-dependent increase in CSF volume worsening the severity of oedema. Oedema was identified primarily in brain regions bordering CSF compartments in mice and humans. The degree of ex vivo tissue swelling was predicted by an osmotic model suggesting that anoxic brain tissue possesses a high intrinsic osmotic potential. This osmotic process was temperature-dependent, proposing an additional mechanism for the beneficial effect of therapeutic hypothermia. These observations show that CSF is a primary source of oedema fluid in anoxic brain. This novel insight offers a mechanistic basis for the future development of alternative strategies to prevent cerebral oedema formation after cardiac arrest.
Diagnostic accuracy of cerebrospinal fluid biomarkers in genetic prion diseases
Authors: Schmitz Matthias , Villar-Piqué Anna , Hermann Peter , Escaramís Geòrgia , Calero Miguel , Chen Cao , Kruse Niels , Cramm Maria , Golanska Ewa , Sikorska Beata , Liberski Pawel P , Pocchiari Maurizio , Lange Peter , Stehmann Christiane , Sarros Shannon , Martí Eulàlia , Baldeiras Inês , Santana Isabel , Žáková Dana , Mitrová Eva , Dong Xiao-Ping , Collins Steven , Poleggi Anna , Ladogana Anna , Mollenhauer Brit , Kovacs Gabor G , Geschwind Michael D , Sánchez-Valle Raquel , Zerr Inga , Llorens Franc
Published: September 2021

Genetic prion diseases are a rare and diverse group of fatal neurodegenerative disorders caused by pathogenic sequence variations in the prion protein gene, PRNP. Data on CSF biomarkers in patients with genetic prion diseases are limited and conflicting results have been reported for unclear reasons.

Here, we aimed to analyse the diagnostic accuracy of CSF biomarkers currently used in prion clinical diagnosis in 302 symptomatic genetic prion disease cases from 11 prion diagnostic centres, encompassing a total of 36 different pathogenic sequence variations within the open reading frame of PRNP.

CSF samples were assessed for the surrogate markers of neurodegeneration, 14-3-3 protein (14-3-3), total-tau protein (t-tau) and α-synuclein and for prion seeding activity through the real-time quaking-induced conversion assay. Biomarker results were compared with those obtained in healthy and neurological controls. For the most prevalent PRNP pathogenic sequence variations, biomarker accuracy and associations between biomarkers, demographic and genetic determinants were assessed. Additionally, the prognostic value of biomarkers for predicting total disease duration from symptom onset to death was investigated.

High sensitivity of the four biomarkers was detected for genetic Creutzfeldt–Jakob disease associated with the E200K and V210I mutations, but low sensitivity was observed for mutations associated with Gerstmann–Sträussler–Scheinker syndrome and fatal familial insomnia. All biomarkers showed good to excellent specificity using the standard cut-offs often used for sporadic Creutzfeldt–Jakob disease. In genetic prion diseases related to octapeptide repeat insertions, the biomarker sensitivity correlated with the number of repeats. New genetic prion disease-specific cut-offs for 14-3-3, t-tau and α-synuclein were calculated. Disease duration in genetic Creutzfeldt–Jakob disease-E200K, Gerstmann–Sträussler–Scheinker-P102L and fatal familial insomnia was highly dependent on PRNP codon 129 MV polymorphism and was significantly associated with biomarker levels.

In a large cohort of genetic prion diseases, the simultaneous analysis of CSF prion disease biomarkers allowed the determination of new mutation-specific cut-offs improving the discrimination of genetic prion disease cases and unveiled genetic prion disease-specific associations with disease duration.
Acetaldehyde induces NER repairable mutagenic DNA lesions
Authors: Sonohara Yuina , Takatsuka Reine , Masutani Chikahide , Iwai Shigenori , Kuraoka Isao
Published: September 2021

Nucleotide excision repair (NER) is a repair mechanism that removes DNA lesions induced by UV radiation, environmental mutagens and carcinogens. There exists sufficient evidence against acetaldehyde suggesting it to cause a variety of DNA lesions and be carcinogenic to humans. Previously, we found that acetaldehyde induces reversible intra-strand GG crosslinks in DNA similar to those induced by cis-diammineplatinum(II) that is subsequently repaired by NER. In this study, we analysed the repairability by NER mechanism and the mutagenesis of acetaldehyde. In an in vitro reaction setup with NER-proficient and NER-deficient xeroderma pigmentosum group A (XPA) cell extracts, NER reactions were observed in the presence of XPA recombinant proteins in acetaldehyde-treated plasmids. Using an in vivo assay with living XPA cells and XPA-correcting XPA cells, the repair reactions were also observed. Additionally, it was observed that DNA polymerase eta inserted dATP opposite guanine in acetaldehyde-treated oligonucleotides, suggesting that acetaldehyde-induced GG-to-TT transversions. These findings show that acetaldehyde induces NER repairable mutagenic DNA lesions.
Neuroanatomical Profile of Young Females with Fragile X Syndrome: A Voxel-Based Morphometry Analysis
Authors: Lee Cindy H , Bartholomay Kristi L , Marzelli Matthew J , Miller Jonas G , Bruno Jennifer L , Lightbody Amy A , Reiss Allan L
Published: September 2021

Fragile X syndrome is a genetic condition associated with alterations in brain and subsequent cognitive development. However, due to a milder phenotype relative to males, females with fragile X syndrome are underrepresented in research studies. In the current study, we investigate neuroanatomical differences in young females (age range: 6.03–16.32 years) with fragile X syndrome (N = 46) as compared to age-, sex-, and verbal abilities-matched participants (comparison group; N = 35). Between-group analyses of whole-brain and regional brain volumes were assessed using voxel-based morphometry. Results demonstrate significantly larger total gray and white matter volumes in girls with fragile X syndrome compared to a matched comparison group (Ps < 0.001). In addition, the fragile X group showed significantly larger gray matter volume in a bilateral parieto-occipital cluster and a right parieto-occipital cluster (Ps < 0.001). Conversely, the fragile X group showed significantly smaller gray matter volume in the bilateral gyrus rectus (P < 0.03). Associations between these regional brain volumes and key socio-emotional variables provide insight into gene–brain–behavior relationships underlying the fragile X syndrome phenotype in females. These findings represent the first characterization of a neuroanatomical phenotype in a large sample of girls with fragile X syndrome and expand our knowledge about potential neurodevelopmental mechanisms underlying cognitive–behavioral outcomes in this condition.
A Multicenter, Prospective, Observational, Cohort-Controlled Study of Clinical Outcomes Following Coronavirus Disease 2019 (COVID-19) Convalescent Plasma Therapy in Hospitalized Patients With COVID-19
Authors: Chauhan Lakshmi , Pattee Jack , Ford Joshay , Thomas Chris , Lesteberg Kelsey , Richards Eric , Bernas Carl A , Loi Michele , Dumont Larry , Annen Kyle , Berg Mary , Zirbes Mercedes , Knight Vijaya , Miller Amanda , Jenkins Timothy C , Bennett Tellen D , Monkowski Daniel , Boxer Rebecca S , Beckham J David
Published: September 2021

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high inpatient mortality and morbidity throughout the world. COVID-19 convalescent plasma (CCP) has been utilized as a potential therapy for patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. This study evaluated the outcomes of hospitalized patients with COVID-19 treated with CCP in a prospective, observational, multicenter trial.

Methods

From April through August 2020, hospitalized patients with COVID-19 at 16 participating hospitals in Colorado were enrolled and treated with CCP and compared with hospitalized patients with COVID-19 who were not treated with convalescent plasma. Plasma antibody levels were determined following the trial, given that antibody tests were not approved at the initiation of the trial. CCP-treated and untreated hospitalized patients with COVID-19 were matched using propensity scores followed by analysis for length of hospitalization and inpatient mortality.

Results

A total of 542 hospitalized patients with COVID-19 were enrolled at 16 hospitals across the region. A total of 468 hospitalized patients with COVID-19 were entered into propensity score matching with 188 patients matched for analysis in the CCP-treatment and control arms. Fine-Gray models revealed increased length of hospital stay in CCP-treated patients and no change in inpatient mortality compared with controls. In subgroup analysis of CCP-treated patients within 7 days of admission, there was no difference in length of hospitalization and inpatient mortality.

Conclusions

These data show that treatment of hospitalized patients with COVID-19 treated with CCP did not significantly improve patient hospitalization length of stay or inpatient mortality.
Risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission Among Air Passengers in China
Authors: Hu Maogui , Wang Jinfeng , Lin Hui , Ruktanonchai Corrine W , Xu Chengdong , Meng Bin , Zhang Xin , Carioli Alessandra , Feng Yuqing , Yin Qian , Floyd Jessica R , Ruktanonchai Nick W , Li Zhongjie , Yang Weizhong , Tatem Andrew J , Lai Shengjie
Published: September 2021

Background

Modern transportation plays a key role in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and new variants. However, little is known about the exact transmission risk of the virus on airplanes.

Methods

Using the itinerary and epidemiological data of coronavirus disease 2019 (COVID-19) cases and close contacts on domestic airplanes departing from Wuhan city in China before the lockdown on 23 January 2020, we estimated the upper and lower bounds of overall transmission risk of COVID-19 among travelers.

Results

In total, 175 index cases were identified among 5797 passengers on 177 airplanes. The upper and lower attack rates (ARs) of a seat were 0.60% (34/5622, 95% confidence interval [CI] .43–.84%) and 0.33% (18/5400, 95% CI .21–.53%), respectively. In the upper- and lower-bound risk estimates, each index case infected 0.19 (SD 0.45) and 0.10 (SD 0.32) cases, respectively. The seats immediately adjacent to the index cases had an AR of 9.2% (95% CI 5.7–14.4%), with a relative risk 27.8 (95% CI 14.4–53.7) compared to other seats in the upper limit estimation. The middle seat had the highest AR (0.7%, 95% CI .4%–1.2%). The upper-bound AR increased from 0.7% (95% CI 0.5%–1.0%) to 1.2% (95% CI .4–3.3%) when the co-travel time increased from 2.0 hours to 3.3 hours.

Conclusions

The ARs among travelers varied by seat distance from the index case and joint travel time, but the variation was not significant between the types of aircraft. The overall risk of SARS-CoV-2 transmission during domestic travel on planes was relatively low. These findings can improve our understanding of COVID-19 spread during travel and inform response efforts in the pandemic.
Congenital Infection of Severe Acute Respiratory Syndrome Coronavirus 2 With Intrauterine Fetal Death: A Clinicopathological Study With Molecular Analysis
Authors: Lesieur Emmanuelle , Torrents Julia , Fina Frédéric , Zandotti Christine , Blanc Julie , Collardeau-Frachon Sophie , Gazin Céline , Sirgant Delphine , Mezouar Soraya , Otmani Idrissi Myriem , Lepidi Hubert , Bretelle Florence , Mege Jean Louis , Daniel Laurent , Fritih Radia
Published: September 2021

Background

Observations of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from mother to fetus have recently been described in the literature. However, the consequences of such transmission, whether fetal or neonatal, are poorly understood.

Methods

From a case of in utero fetal death at 24+2 weeks of gestation that occurred 7 days after the diagnosis of symptomatic SARS-CoV-2 infection in the mother, we isolated the incriminating virus by immunochemistry and molecular techniques in several fetal tissues, with a variant analysis of the SARS-CoV-2 genome.

Results

The fetal demise could be explained by the presence of placental histological lesions, such as histiocytic intervillositis and trophoblastic necrosis, in addition to fetal tissue damage. We observed mild fetal growth retardation and visceral damage to the liver, causing hepatocellular damage and hemosiderosis. To the best of our knowledge, this is the first report in the literature of fetal demise secondary to maternal–fetal transmission of SARSCoV- 2 with a congenital infection and a pathological description of placental and fetal tissue damage.

Conclusions

SARS-CoV-2 was identified in both specimens using 3 independent techniques (immunochemistry, real-time quantitative polymerase chain reaction, and realtime digital polymerase chain reaction). Furthermore, the incriminating variant has been identified.
Did Brexit Change EU Law?
Authors: Nic Shuibhne Niamh
Published: September 2021

This paper investigates whether the withdrawal of the United Kingdom from the European Union changed EU law. Brexit necessarily animated the law related to and produced by Article 50 TEU. Did it also imprint on fundamental premises of EU law that will continue to shape relations between the Member States and the Union, and between the Union and the wider world? These questions are examined through the examples of the legal force of political decision-making and the legal nature of relationships with third States. At one level, it will be seen that Brexit restored the centrality of Union institutions and processes in the EU law-making that responds to exceptional situations. At the same time, however, it has distorted and/or displaced some of the vital checks and balances that would normally apply. A course correction exploiting a rounded understanding of the effectiveness of EU law and provoking coherent articulation of the legal coordinates of Union membership is urged in response.
130 SEVERITY OF ANASTOMOTIC LEAKAGE AFTER DIFFERENT TYPES OF ESOPHAGECTOMY: A NATIONWIDE COHORT STUDY
Authors: Verstegen Moniek , Slaman Annelijn , Klarenbeek Bastiaan , Berge Henegouwen Mark , Gisbertz Suzanne , Rosman Camiel , van Workum Frans
Published: September 2021

Orringer, McKeown and Ivor Lewis esophagectomy are the most commonly performed procedures for esophageal and gastro-esophageal junction cancer. Anastomotic leakage remains a major problem after all types of esophagectomy and it is currently unknown whether anastomotic leakage severity is different between the types of esophagectomy. The aim of this study was to investigate the relationship between surgical techniques and the severity of anastomotic leakage in patients after Orringer esophagectomy, McKeown esophagectomy or Ivor Lewis esophagectomy.

Methods

All esophageal and gastro-esophageal junction cancer patients with anastomotic leakage after Orringer, McKeown or Ivor Lewis esophagectomy between 2011 and 2019 were selected from the Dutch Upper Gastrointestinal Cancer Audit (DUCA). The primary outcome parameter was a composite endpoint of reoperation, intensive care unit (ICU) readmission and 30-day/in-hospital mortality. Secondary outcome parameters included postoperative complications, re-intervention rate, ICU and hospital length of stay.

Results

Data from 1034 patients with anastomotic leakage after Orringer (n = 287), McKeown (n = 397) and Ivor Lewis esophagectomy (n = 346) were evaluated. The primary endpoint occurred in 36.3% of patients with anastomotic leakage after Orringer esophagectomy, in 55.4% of patients with anastomotic leakage after McKeown esophagectomy and in 61.2% of patients with anastomotic leakage after Ivor Lewis esophagectomy (p < 0.001). When adjusting for potential confounding variables, the sequelae of anastomotic leakage after Orringer and McKeown esophagectomy remained less severe compared to anastomotic leakage after Ivor Lewis esophagectomy (OR 0.28, 95% CI 0.20–0.41, p < 0.001 and OR 0.71, 95% CI 0.52–0.97, p = 0.031, respectively).

Conclusion

Consequences of anastomotic leakage are most severe after Ivor Lewis esophagectomy, moderately severe after McKeown esophagectomy and least severe after Orringer esophagectomy. This study demonstrated that not only the incidence, but also the severity of anastomotic leakage should be considered in current clinical practice and in studies that compare leakage rates between different surgical techniques of esophagectomy.
149 DIFFERENCES IN TRANSABDOMINAL ULTRASONOGRAPHIC PARAMETERS AMONG PATIENTS COMPLAINING OF ESOPHAGEAL DYSPHAGIA
Authors: Manabe Noriaki , Ayaki Maki , Nakamura Jun , Fujita Minoru , Suehiro Mitsuhiko , Kawamoto Hirofumi , Kamada Tomoari , Yamatsuji Tomoki , Naomoto Yoshio , Haruma Ken
Published: September 2021

Dysphagia is a symptom suggestive of severe underlying pathology, although its causes include organic and non-organic disorders. A balance must be struck between the potential complications of any invasive investigation and its diagnostic utility, especially for elderly patients with dysphagia. The aim of this study was to investigate whether transabdominal ultrasonography (TUS) can differentiate among patients complaining of esophageal dysphagia including achalasia, distal esophageal spasms (DES), neoplasms involving the esophagogastric junction (EGJ) and healthy controls.

Methods

All patients complained of esophageal dysphagia, while healthy controls had no symptoms originating from esophagus. TUS was performed in 50 patients with achalasia, 17 DES patients, 10 patients with neoplasms, and 39 sex- and age-matched controls. All studies were performed with a 3.5 MHz real time curved array scanner and using an electronic caliper to measure esophageal wall thickness and the maximum esophageal diameter at 3 cm from EGJ. Manometric diagnoses were made based on the Chicago classification ver.3. The cutoff value of each TUS parameter was then calculated. Specificity and sensitivity in making a diagnosis of each disease were determined.

Results

There were significantly differences in the TUS parameters among four groups (Fig). The cutoff value of diameter of esophageal lumen to differentiate achalasia from other 3 groups was calculated as 13.1 mm (sensitivity, 0.96; specificity, 0.93), with an area under the curve (AUC) of 0.99, and that of esophageal wall thickness to differentiate both the tumor and DES groups from the other two groups was 3.5 mm (sensitivity, 0.64; specificity, 0.62), respectively. Using these parameters, sensitivity and specificity of diagnosis was 0.56 and 0.95 in achalasia, 1.00 and 0.24 in DES, and 1.00 and 0.21 in tumors.

Conclusion

TUS is a useful, non-invasive diagnostic aid in differentiating patients with primary achalasia from those with other causes of dysphagia.
152 SURGICAL PROCEDURE AND OUTCOME OF MEDIASTINOSCOPIC RADICAL ESOPHAGECTOMY FOR ESOPHAGOGASTRIC JUNCTION CANCER
Authors: Shiozaki Atsushi , Fujiwara Hitoshi , Konishi Hirotaka , Kudou Michihiro , Shimizu Hiroki , Arita Tomohiro , Kosuga Toshiyuki , Morimura Ryo , Kuriu Yoshiaki , Ikoma Hisashi , Kubota Takeshi , Okamoto Kazuma , Otsuji Eigo
Published: September 2021

We started performing mediastinal lymph node dissection by a laparoscopic transhiatal approach (LTHA) in 2009. To date, 371 patients had undergone our method during various esophageal surgical procedures, including esophagogastric junction cancer (EGJC). Furthermore, we started performing single-port mediastinoscopic cervical approach in 2014, and developed a simple technique for transmediastinal radical esophagectomy (TMr) without thoracic approach (258 cases). Forty patients with EGJC were also treated by TMr.

Methods

Left single-port mediastinoscopic cervical approach was performed with pneumomediastinum. Mainly for advanced SCC, upper mediastinal lymph node dissection including recurrent laryngeal nerve LNs was performed with intraoperative monitoring using NIM system. Next, LTHA was performed for en bloc mediastinal lymph node dissection. The esophageal hiatus was opened, and working space was secured by Long Retractors. The posterior plane of the pericardium was extended. The posterior side of LNs was then separated. Finally, while lifting LNs like a membrane, they were resected from bilateral mediastinal pleura. Reconstruction with narrow gastric conduit was performed through substernal tract.

Results

Patients with EGJC performed TMr were analyzed (n = 40, SCC/Adeno/Others = 21/17/2). Upper mediastinal lymph node metastasis was found in 6 cases (SCC/Adeno = 3/3), middle mediastinal lymph node metastasis was found in 2 cases (SCC/Adeno = 1/1), and all of them had advanced tumors. Their perioperative outcome were compared with those performed the right thoracotomy (n = 41). The operative time and bleeding were decreased by TMr. The number of resected mediastinal lymph nodes, pR0 rate, and mediastinal recurrence in the two groups were not different. In 95.0% of patients treated by TMr, extubation was performed at 0 POD. Postoperative respiratory complications was decreased by TMr (TMr:7.5%, thoracotomy:17.1%).

Conclusion

This procedure, TMr, resulted in a good surgical view, safe en-bloc mediastinal lymph node dissection, and the decrease of postoperative respiratory complications in patients with EGJC.
169 THE RELATIONSHIPS BETWEEN SYMPTOMS, REFLUX PH VALUES, AND EXTENT OF REFLUX IN PATIENTS WITH P-CAB-RESISTANT NERD
Authors: Kawami Noriyuki , Hoshino Shintaro , Hoshikawa Yoshimasa , Takenouchi Nana , Hanada Yuriko , Tanabe Tomohide , Koeda Mai , Monma Eri , Kaise Mitsuru , Iwakiri Katsuhiko
Published: September 2021

In patients with proton pump inhibitor-resistant non erosive reflux disease (NERD) having symptoms associated with liquid reflux, there are reports that reflux symptoms are more likely to be caused by the proximal extent of the reflux and reflux where pH <5. The objective of this study was to investigate the relationships between symptoms, reflux pH values, and the extent of reflux in patients with potassium-competitive acid blocker (P-CAB)-resistant NERD.

Methods

The subjects were 20 patients with P-CAB-resistant NERD whose symptoms did not improve even after administration of P-CAB (vonoprazan 20 mg/day) for 2–4 weeks. Their symptom index was positive for liquid reflux in impedance–pH monitoring. We investigated reflux pH values in symptomatic and asymptomatic reflux events, proportion of symptomatic reflux events according to the reflux pH value (pH <5 or ≥ 5), proportion of symptomatic reflux events at each impedance site, and proportion of symptomatic reflux events at each impedance site according to the reflux pH value (pH <5 or ≥ 5).

Results

About 60% of the symptomatic reflux events were caused by reflux with pH ≥5 in patients with P-CAB-resistant NERD. The median reflux pH value for total reflux events was 5.3 and that for symptomatic reflux events was 5.2. The proportion of symptomatic reflux events caused by reflux with pH <5 was significantly higher than that caused by reflux with pH ≥5. Symptomatic reflux events for reflux with pH <5 are more likely to be caused by proximal extent. There was no difference in the proportion of symptomatic reflux events for reflux with pH ≥5 at each reflux extent site.

Conclusion

In patients with P-CAB-resistant NERD, their symptoms were often caused by reflux with pH ≥5. A difference in the relationship between the reflux extent site and appearance of symptoms was observed according to the reflux pH value.
177 CT RADIOMICS BASED ON MACHINE LEARNING PREDICTING PATHOLOGIC COMPLETE RESPONSE AFTER NEOADJUVANT CHEMORADIOTHERAPY FOR ESOPHAGEAL CANCER
Authors: Leng Xue-Feng , Wang Qi-Feng , Lang Jin-Yi , Li Tao , Han Yong-Tao , Peng Lin , Yue H , Cheng J , Liu J
Published: September 2021

Neoadjuvant chemoradiotherapy (nCRT) has become the standard treatment for patients with locally advanced squamous cell esophageal cancer (LA-ESCC). Patients with the complete pathologic response (pCR) have significantly improved long-term survival. All efforts should be to improve the accuracy of predicting pCR. In this study, we investigate the use of radiomics based on machine learning to identify the pathologic complete response of patients with esophageal squamous cell carcinoma (ESCC) based on Computed Tomography (CT).

Methods

The study included 155 patients with pathologically confirmed LA-ESCC. All 155 patients underwent simulation CT before nCRT, Quantitative radiomics features were extracted from CT images of each patient. To explore the relationship between radiomics features and the pCR, we used five-fold cross validation to classify the training and the testing cohorts. The Least Absolute Shrinkage and Selectionator operator (Lasso) were used to select features useful for the grading of pCR in the training cohort. Different models were measured in the training cohort using accuracy, sensitivity, specificity, and area under the curve of the receiver operating characteristic curve (AUC).

Results

There were 155 patients. The pretreatment clinical stage was II in 16 patients (10.3%), III in 132 (85.2%), and IV in 7 (4.5%). Pathologic response was complete in 69 patients (44.5%), near-partial complete in 86 (55.5%). A total of 2193 radiomics features were extracted in the training set. After the use of statistical dimensionality reduction, five radiomics features were selected by Lasso to build radiomics signature. Prediction models for pCR were developed, and the model was able to predict pCR well in the training set(AUC = 0.902). In the testing cohorts, the model had a good performance in predicting pCR (AUC = 0.78).

Conclusion

This study showed that CT-based radiomics features could be used as biomarkers to predict the complete pathological response of esophageal cancer underwent Neoadjuvant chemoradiotherapy.