bluuebunny/crossref_metadata_2025_split huggingface dataset:
Junctional instability in neuroepithelium and network hyperexcitability in a focal cortical dysplasia human model
Authors: Avansini Simoni H , Puppo Francesca , Adams Jason W , Vieira Andre S , Coan Ana C , Rogerio Fabio , Torres Fabio R , Araújo Patricia A O R , Martin Mariana , Montenegro Maria A , Yasuda Clarissa L , Tedeschi Helder , Ghizoni Enrico , França Andréa F E C , Alvim Marina K M , Athié Maria C , Rocha Cristiane S , Almeida Vanessa S , Dias Elayne V , Delay Lauriane , Molina Elsa , Yaksh Tony L , Cendes Fernando , Lopes Cendes Iscia , Muotri Alysson R 
Published: December 2021

Abstract
Focal cortical dysplasia is a highly epileptogenic cortical malformation with few treatment options.
Here, we generated human cortical organoids from patients with focal cortical dysplasia type II. Using this human model, we mimicked some focal cortical dysplasia hallmarks, such as impaired cell proliferation, the presence of dysmorphic neurons and balloon cells, and neuronal network hyperexcitability. Furthermore, we observed alterations in the adherens junctions zonula occludens-1 and partitioning defective 3, reduced polarization of the actin cytoskeleton, and fewer synaptic puncta. Focal cortical dysplasia cortical organoids showed downregulation of the small GTPase RHOA, a finding that was confirmed in brain tissue resected from these patients. Functionally, both spontaneous and optogenetically-evoked electrical activity revealed hyperexcitability and enhanced network connectivity in focal cortical dysplasia organoids.
Taken together, our findings suggest a ventricular zone instability in tissue cohesion of neuroepithelial cells, leading to a maturational arrest of progenitors or newborn neurons, which may predispose to cellular and functional immaturity and compromise the formation of neural networks in focal cortical dysplasia.
Identifying Sepsis From Foodborne Hospitalization: Incidence and Hospitalization Cost by Pathogen
Authors: Ahn Jae Wan , Scallan Walter Elaine , White Alice E , McQueen R Brett , Hoffmann Sandra 
Published: December 2021

AbstractBackgroundSepsis causes a major health burden in the United States. To better understand the role of sepsis as a driver of the burden and cost of foodborne illness in the United States, we estimated the frequency and treatment cost of sepsis among US patients hospitalized with 31 pathogens commonly transmitted through food or with unspecified acute gastrointestinal illness (AGI).MethodsUsing data from the National Inpatient Sample from 2012 to 2015, we identified sepsis hospitalizations using 2 approaches—explicit ICD-9-CM codes for sepsis and a coding scheme developed by Angus that identifies sepsis using specific ICD-9-CM diagnosis codes indicating an infection plus organ failure. We examined differences in the frequency and the per-case cost of sepsis across pathogens and AGI and estimated total hospitalization costs using prior estimates of foodborne hospitalizations.ResultsUsing Explicit Sepsis Codes, sepsis hospitalizations accounted for 4.6% of hospitalizations with a pathogen commonly transmitted through food or unspecified AGI listed as a diagnosis; this was 33.2% using Angus Sepsis Codes. The average per-case cost was $35 891 and $20 018, respectively. Applying the proportions of hospitalizations with sepsis from this study to prior estimates of the number foodborne hospitalizations, the total annual cost was $248 million annually using Explicit Sepsis Codes and $889 million using Angus Sepsis Codes.ConclusionsSepsis is a serious complication among patients hospitalized with a foodborne pathogen infection or AGI resulting in a large burden of illness. Hospitalizations that are diagnosed using explicit sepsis codes are more severe and costly, but likely underestimate the burden of foodborne sepsis.
Coronavirus Disease 2019 (COVID-19) Breakthrough Infection and Post-Vaccination Neutralizing Antibodies Among Healthcare Workers in a Referral Hospital in Tokyo: A Case-Control Matching Study
Authors: Yamamoto Shohei , Maeda Kenji , Matsuda Kouki , Tanaka Akihito , Horii Kumi , Okudera Kaori , Takeuchi Junko S , Mizoue Tetsuya , Konishi Maki , Ozeki Mitsuru , Sugiyama Haruhito , Aoyanagi Nobuyoshi , Mitsuya Hiroaki , Sugiura Wataru , Ohmagari Norio 
Published: December 2021

Abstract

Background
While increasing coverage of effective vaccines against coronavirus disease 2019 (COVID-19), emergent variants raise concerns about breakthrough infection. Data are limited, however, whether breakthrough infection during the epidemic of the variant is ascribed to insufficient vaccine-induced immunogenicity.

Methods
We describe incident COVID-19 in relation to the vaccination program among workers of a referral hospital in Tokyo. During the predominantly Delta epidemic, we followed 2415 fully vaccinated staff (BNT162b2) for breakthrough infection and selected 3 matched controls. We measured post-vaccination neutralizing antibodies against the wild-type, Alpha (B.1.1.7), and Delta (B.1.617.2) strains using live viruses and anti-spike antibodies using quantitative assays, and compared them using the generalized estimating equation model between the 2 groups.

Results
No COVID-19 cases occurred 1–2 months after the vaccination program during the fourth epidemic wave in Japan, dominated by the Alpha variant, while 22 cases emerged 2–4 months after the vaccination program during the fifth wave, dominated by the Delta variant. In the vaccinated cohort, all 17 cases of breakthrough infection were mild or asymptomatic and participants had returned to work early. There was no measurable difference between cases and controls in post-vaccination neutralizing antibody titers against the wild-type, Alpha, Delta, and anti-spike antibody titers, while neutralizing titers against the variants were considerably lower than those against the wild-type.

Conclusions
Post-vaccination neutralizing antibody titers were not decreased among patients with breakthrough infection relative to their controls under the Delta variant outbreak. The result points to the importance of infection-control measures in the post-vaccination era, irrespective of immunogenicity profile.
How much progress have we made?: a 20-year experience regarding esophageal stents for the palliation of malignant dysphagia
Authors: Kumar Shria , Bahdi Firas , Emelogu Ikenna K , Yu Abraham C , Coronel Martin , Ge Philip S , Coronel Emmanuel , Ajani Jaffer A , Weston Brian , Lynch Patrick , Ross William A , Lee Jeffrey H 
Published: December 2021

Summary
Esophageal stents are widely used for the palliation of malignant esophageal obstruction. Advances in technology have made esophageal stenting technically feasible and widespread for such obstruction, but complications remain frequent. We present outcomes of a large cohort undergoing esophageal stent placement for malignant esophageal obstruction at a tertiary care cancer center. Patients who underwent placement of esophageal stents for malignancy-related esophageal obstruction between 1 January 2001 and 31 July 2020 were identified. Exclusion criteria included stents placed for benign stricture, fistulae, obstruction of proximal esophagus (proximal to 24 cm from incisors), or post-surgical indications. Patient charts were reviewed for demographics, procedure and stent characteristics, complications, and follow-up. A total of 242 patients underwent stent placement (median age: 64 years, 79.8% male). The majority, 204 (84.3%), had esophageal cancer. During the last two decades, there has been an increasing trend in the number of esophageal stents placed. Though plastic stents were previously used, these are no longer utilized. Complications are frequent and include early complications of pain in 68 (28.1%) and migration in 21 (8.7%) and delayed complications of recurrent symptoms of dysphagia in 46 (19.0%) and migration in 26 (10.7%). Over the study period, there has not been a significant improvement in the rate of complications. During follow-up, 92 (38%) patients required other enteral nutrition modalities after esophageal stent placement. No patient, treatment, or stent characteristics were significantly associated with stent complication or outcome. Esophageal stent placement is an increasingly popular method for palliation of malignant dysphagia. However, complications, particularly pain, migration, and recurrent symptoms of dysphagia are common. Almost 40% of patients may also require other methods of enteral access after esophageal stent placement. Given the high complication rates and suboptimal outcomes, removable stents should be considered as first-line in the case of poor palliative response.
Geriatric patients with esophageal motility disorders benefit more from minimally invasive peroral endoscopic myotomy: a multicenter study in Japan
Authors: Ujiie Naoto , Sato Hiroki , Fujiyoshi Mary Raina Angeli , Tanaka Shinwa , Shiwaku Hironari , Shiota Junya , Ogawa Ryo , Yokomichi Hiroshi , Kamei Takashi , Inoue Haruhiro 
Published: December 2021

Summary
Geriatric patients with existing studies on the safety and efficacy of peroral endoscopic myotomy (POEM) for achalasia involve small sample sizes and single institutions. However, multi-center, large-scale data analyses are lacking. The study aimed to clarify the characteristics of geriatric patients with esophageal motility disorders (EMDs) and determine the procedure-related outcomes and clinical course following POEM. This cohort study included 2,735 patients with EMDs who were treated at seven Japanese facilities between 2010 and 2019. The patients’ characteristics and post-POEM clinical courses were compared between the geriatric (age ≥ 75 years; n = 321) and non-geriatric (age &lt; 75 years; n = 2,414) groups. Compared with the non-geriatric group, the geriatric group had higher American Society of Anesthesiologists physical status scores; more recurrent cases; lower incidence of chest pain; and higher incidence of type III achalasia, distal esophageal spasm, and Jackhammer esophagus. Furthermore, the incidence of sigmoid esophagus was higher, although esophageal dilation was not severe in this group. POEM was safe and effective for geriatric patients with treatment-naïve and recurrent EMDs. Furthermore, compared with the non-geriatric group, the geriatric group had lower post-POEM Eckardt scores, fewer complaints of refractory chest pain, and a lower incidence rate of post-POEM reflux esophagitis. Geriatric patients are characterized by worse clinical conditions, more spastic disorders, and greater disease progression of EMDs, which are also the indications for minimally invasive POEM. POEM is more beneficial in geriatric patients as it has lowering symptom scores and incidence rates of reflux esophagitis.
Bilateral internal thoracic artery coronary grafting: risks and benefits in elderly patients
Authors: Zhou Zhuoming , Fu Guangguo , Huang Suiqing , Chen Sida , Liang Mengya , Wu Zhongkai 
Published: December 2021

Abstract

Aims
Whether bilateral internal thoracic artery (BITA) grafting benefits elderly patients in coronary artery bypass grafting (CABG) remains unclear since they tend to have a limited life expectancy and severe comorbidities. We aim to evaluate the outcomes of BITA vs. single internal thoracic artery (SITA) grafting in elderly patients.

Methods and results
A meta-analysis was performed by database searching until May 2021. Studies comparing BITA and SITA grafting among elderly patients were included. One randomized controlled trial, nine propensity score matching, and six unmatched studies were identified, with a total of 18 146 patients (7422 received BITA grafting and 10 724 received SITA grafting). Compared with SITA grafting, BITA grafting had a higher risk of deep sternal wound infection (DSWI) [odds ratio: 1.67; 95% confidence interval (CI): 1.22–2.28], and this risk could not be significantly reduced by the skeletonization technique. Meanwhile, BITA grafting was associated with a higher long-term survival [hazard ratio: 0.83; 95% CI: 0.77–0.90], except for the octogenarian subgroup. Reconstructed Kaplan–Meier survival curves revealed 4-year, 8-year, and 12-year overall survival rates of 85.5%, 66.7%, and 45.3%, respectively, in the BITA group and 79.3%, 58.6%, and 34.9%, respectively, in the SITA group. No significant difference was observed in early mortality, perioperative myocardial infarction, perioperative cerebral vascular accidents, or re-exploration for bleeding.

Conclusion
Compared with SITA grafting, BITA grafting could provide a long-term survival benefit for elderly patients, although this benefit remained uncertain in octogenarians. Meanwhile, elderly patients who received BITA were associated with a higher risk of DSWI and such a risk could not be eliminated by the skeletonization technique.
The Forgotten Liberal Social Reform? Marriage with a Deceased Wife’s Sister, Political Nonconformity and the New Liberalism in Edwardian Britain
Authors: Barrie David G 
Published: December 2021

Abstract
This article examines why Victorian Britain’s longest-running political controversy—the sixty-four-year campaign to legalise marriage between a widower and his deceased wife’s sister—was finally resolved in 1907. It explores why the Liberal government decided to support reform, what strategies it adopted and how it was able to force a deceased wife’s sister bill through an intransigent House of Lords that had, for more than half a century, succeeded in blocking similar bills. The article recognises that a multitude of factors—social, theological, imperial and legal—shaped opinion on the issue. Nonetheless, it argues that the Liberal government’s backing for marriage with a deceased wife’s sister (MDWS) should be viewed, in terms of its hegemonic public presentation, as the forgotten Liberal social reform. In keeping with the emerging New Liberalism, MDWS was packaged primarily as a social relief measure that spoke to the Liberal Party’s growing interest in the poor, child welfare, social justice, women’s rights and state support for workers. The commitment to easing the plight of those affected by the existing prohibition was real, but behind the public rhetoric lay a desire to stem nonconformist discontent among the Liberal Party’s electoral base, and an evolving constitutional crisis between the houses of parliament which gave the issue greater symbolic significance. For many peers, reform had become more than just palatable or desirable. It was necessary in the light of a change in colonial marriage law that had sought to address colonial grievances, promote imperial unity and better safeguard inherited wealth and social status.
Subduction earthquake sequences in a non-linear visco-elasto-plastic megathrust
Authors: Dal Zilio Luca , Lapusta Nadia , Avouac Jean-Philippe , Gerya Taras 
Published: December 2021

SUMMARYWe present a 2-D thermomechanical computational framework for simulating earthquake sequences in a non-linear visco-elasto-plastic compressible medium. The method is developed for a plane-strain problem and incorporates an invariant formulation of the classical rate- and state-dependent friction law and an adaptive time-stepping, which allows the time step to vary by many orders of magnitude during a simulation. Long-term tectonic convergence is imposed by displacing a boundary at a constant rate, whereas temperature-dependent viscosity is solved using a rapidly converging Newton–Raphson scheme. The 2-D volume is discretized using finite differences on a fully staggered grid and marker-in-cell techniques. An adaptive free-surface approximation is used to modulate the air viscosity with the time step, which allows stresses to vanish on the free surface during the propagation of fast slipping events. We present a set of increasingly complex models in which we investigate how inertia, radiation damping, thermally activated non-linear rheology and off-megathrust splay-fault events affect sequences of seismic and aseismic slip on a simplified subduction megathrust. The new method provides a unique computational framework to analyse earthquake sequences and to connect forearc deformation with the dynamic properties of the megathrust, thus providing a physical link between observations spanning from slow interseismic strain accumulation to localized coseismic slip of individual earthquakes and post-seismic viscoelastic relaxation.
Dose- and LET-dependent changes in mouse skin contracture up to a year after either single dose or fractionated doses of carbon ion or gamma rays
Authors: Ando Koichi , Yoshida Yukari , Hirayama Ryoichi , Koike Sachiko , Matsufuji Naruhiro 
Published: December 2021

Abstract
Time dependence of relative biological effectiveness (RBE) of carbon ions for skin damage was investigated to answer the question of whether the flat distribution of biological doses within a Spread-Out Bragg peak (SOBP) which is designed based on in vitro cell kill could also be flat for in vivo late responding tissue. Two spots of Indian ink intracutaneously injected into the legs of C3H mice were measured by calipers. An equieffective dose to produce 30% skin contraction was calculated from a dose–response curve and used to calculate the RBE of carbon ion beams. We discovered skin contraction progressed after irradiation and then reached a stable/slow progression phase. Equieffective doses decreased with time and the decrease was most prominent for gamma rays and least prominent for 100 keV/μm carbon ions. Survival parameter of alpha but not beta in the linear-quadratic model is closely related to the RBE of carbon ions. Biological doses within the SOBP increased with time but their distribution was still flat up to 1 year after irradiation. The outcomes of skin contraction studies suggest that (i) despite the higher RBE for skin contracture after carbon ions compared to gamma rays, gamma rays can result in a more severe late effect of skin contracture. This is due to the carbon effect saturating at a lower dose than gamma rays, and (ii) the biological dose distribution throughout the SOBP remains approximately the same even one year after exposure.
Bayesian Inference for Estimating Subset Proportions using Differentially Private Counts
Authors: Li Linlin , Reiter Jerome P 
Published: December 2021

Abstract
Recently, several organizations have considered using differentially private algorithms for disclosure limitation when releasing count data. The typical approach is to add random noise to the counts sampled from, for example, a Laplace distribution or symmetric geometric distribution. One advantage of this approach, at least for some differentially private algorithms, is that analysts know the noise distribution and hence have the opportunity to account for it when making inferences about the true counts. In this article, we present Bayesian inference procedures to estimate the posterior distribution of a subset proportion, that is, a ratio of two counts, given the released values. We illustrate the methods under several scenarios, including when the released counts come from surveys or censuses. Using simulations, we show that the Bayesian procedures can result in accurate inferences with close to nominal coverage rates.
The role ofAUX1during lateral root development in the domestication of the model C4 grassSetaria italica
Authors: Tang Sha , Shahriari Mojgan , Xiang Jishan , Pasternak Taras , Igolkina Anna , Aminizade Somayeh , Zhi Hui , Gao Yuanzhu , Roodbarkelari Farshad , Sui Yi , Jia Guanqing , Wu Chuanyin , Zhang Linlin , Zhao Lirong , Li Xugang , Meshcheryakov Georgy , Samsonova Maria , Diao Xianmin , Palme Klaus , Teale William 
Published: December 2021

AbstractC4 photosynthesis increases the efficiency of carbon fixation by spatially separating high concentrations of molecular oxygen from Rubisco. The specialized leaf anatomy required for this separation evolved independently many times. The morphology of C4 root systems is also distinctive and adapted to support high rates of photosynthesis; however, little is known about the molecular mechanisms that have driven the evolution of C4 root system architecture. Using a mutant screen in the C4 model plant Setaria italica, we identify Siaux1-1 and Siaux1-2 as root system architecture mutants. Unlike in S. viridis, AUX1 promotes lateral root development in S. italica. A cell by cell analysis of the Siaux1-1 root apical meristem revealed changes in the distribution of cell volumes in all cell layers and a dependence of the frequency of protophloem and protoxylem strands on SiAUX1. We explore the molecular basis of the role of SiAUX1 in seedling development using an RNAseq analysis of wild-type and Siaux1-1 plants and present novel targets for SiAUX1-dependent gene regulation. Using a selection sweep and haplotype analysis of SiAUX1, we show that Hap-2412TT in the promoter region of SiAUX1 is an allele which is associated with lateral root number and has been strongly selected for during Setaria domestication.
Acquired Factor VIII Inhibitors: A Case Study
Authors: Walradth Eric A 
Published: December 2021

Abstract
The physiology of hemostasis is one of high complexity that involves the initiation, amplification, and propagation of the many moving parts of the hemostatic system and its regulatory mechanisms. It is imperative that clinical laboratory professionals have a strong understanding of the many intricacies of the physiology of coagulation and its in vitro testing. An elongated activated partial thromboplastin time can have several causes, and the correct cause must be elucidated in a timely manner for proper treatment. A mixing study with normal pooled plasma should be performed to evaluate for the presence of an inhibitor vs factor deficiency. Factor inhibitors, specifically factor VIII in this case study, should be titered so that the clinician can decide which treatment may work best for the patient. Continued monitoring of factor levels and inhibitor titers should be conducted to follow the resolution or progression of inhibitor presence.