bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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 &lt; 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 &lt; 0.001). Conversely, the fragile X group showed significantly smaller gray matter volume in the bilateral gyrus rectus (P &lt; 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

Abstract

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

Abstract

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

Abstract

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

Abstract
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

Abstract

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 &lt; 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 &lt; 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

Abstract

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

Abstract

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

Abstract

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 &lt;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 &lt;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 &lt;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 &lt;5 was significantly higher than that caused by reflux with pH ≥5. Symptomatic reflux events for reflux with pH &lt;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.