bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality assurance of radiotherapy in the ongoing EORTC 1420 “Best of” trial for early stage oropharyngeal, supraglottic and hypopharyngeal carcinoma: results of the benchmark case procedure
Authors: Stelmes J-J , Vu E. , Grégoire V. , Simon C. , Clementel E. , Kazmierska J. , Grant W. , Ozsahin M. , Tomsej M. , Vieillevigne L. , Fortpied C. , Hurkmans E. C. , Branquinho A. , Andratschke N. , Zimmermann F. , Weber D.-C. 
Published: May 2021

Abstract
Introduction
The current phase III EORTC 1420 Best-of trial (NCT02984410) compares the swallowing function after transoral surgery versus intensity modulated radiotherapy (RT) in patients with early-stage carcinoma of the oropharynx, supraglottis and hypopharynx. We report the analysis of the Benchmark Case (BC) procedures before patient recruitment with special attention to dysphagia/aspiration related structures (DARS).

Materials and methods
Submitted RT volumes and plans from participating centers were analyzed and compared against the gold-standard expert delineations and dose distributions. Descriptive analysis of protocol deviations was conducted. Mean Sorensen-Dice similarity index (mDSI) and Hausdorff distance (mHD) were applied to evaluate the inter-observer variability (IOV).

Results
65% (23/35) of the institutions needed more than one submission to achieve Quality assurance (RTQA) clearance. OAR volume delineations were the cause for rejection in 53% (40/76) of cases. IOV could be improved in 5 out of 12 OARs by more than 10 mm after resubmission (mHD). Despite this, final IOV for critical OARs in delineation remained significant among DARS by choosing an aleatory threshold of 0.7 (mDSI) and 15 mm (mHD).

Conclusions
This is to our knowledge the largest BC analysis among Head and neck RTQA programs performed in the framework of a prospective trial. Benchmarking identified non-common OARs and target delineations errors as the main source of deviations and IOV could be reduced in a significant number of cases after this process. Due to the substantial resources involved with benchmarking, future benchmark analyses should assess fully the impact on patients’ clinical outcome.
Clinical characteristics and risk factors for culture-negative periprosthetic joint infections
Authors: Watanabe Shintaro , Kobayashi Naomi , Tomoyama Akito , Choe Hyonmin , Yamazaki Etsuko , Inaba Yutaka 
Published: May 2021

Abstract
Background
Culture-negative periprosthetic joint infections (PJIs) can complicate diagnosis and management of PJI. This study aimed to identify risk factors for culture-negative PJI and differences in clinical characteristics between culture-positive and culture-negative PJI group.

Methods
This retrospective, cross-sectional study evaluated PJI cases obtained between January 2013 and October 2019 at our institution. These PJI cases were divided into culture-positive and culture-negative groups and then compared. The demographics, laboratory findings, and details of patient’s clinical characteristics were investigated. Univariate and multivariate logistic regression analysis were performed to investigate risk factors for culture-negative PJI.

Results
A total of 109 PJI cases were included in the analysis: 82 (75%) culture-positive and 27 (25%) culture-negative. The mean serum white blood cell (WBC) count, C-reactive protein level, and erythrocyte sedimentation rate in the culture-negative group were significantly lower than those in the culture-positive group (p < 0.05). There were no significant differences between the two groups regarding history of prior antibacterial administration or treatment success rates. Multivariate analysis identified a low serum WBC count as a risk factor for culture-negative PJI (odds ratio = 0.78; 95% confidence interval [CI] = 0.63–0.97; p = 0.027).

Conclusions
A low serum WBC count is a risk factor for culture-negative PJI, but prior antimicrobial therapy is not. The results suggest that PJI cases with lower levels of systemic inflammation are likely to be culture-negative; therefore, the possibility of a culture-negative result should be considered in suspected cases of PJI with low inflammatory markers, regardless of prior antibiotic exposure.
The predictive value of creatinine clearance for mortality in patients undergoing revascularization
Authors: Ram Eilon , Beckerman Pazit , Segev Amit , Shlomo Nir , Atlas-Lazar Abigail , Sternik Leonid , Raanani Ehud 
Published: May 2021

Abstract
Background
Renal function plays a significant role in the prognosis and management of patients with multi-vessel coronary artery disease (CAD) referred for revascularization. Current data lack precise risk stratification using estimated glomerular filtration rate (eGFR) and creatinine clearance.

Methods
This prospective study includes a three-year follow-up of 1112 consecutive patients with multi-vessel CAD enrolled in the 22 hospitals in Israel that perform coronary angiography.

Results
The Mayo formula yielded the highest mean eGFR (90 ± 26 mL/min per 1.73m2) and chronic kidney disease-epidemiology collaboration (CKD-EPI) the lowest (76 ± 24 mL/min per 1.73m2). Consequently, the Mayo formula classified more patients (56%) as having normal renal function. There was a significant and strong correlation between the values obtained from all five formulas using Cockcroft-Gault as the reference formula: Mayo: r = 0.80, p < 0.001; CKD-EPI: r = 0.87, p < 0.001; modification of diet in renal disease (MDRD): r = 0.84, p < 0.001; inulin clearance-based: r = 0.99, p < 0.001). Multivariable analysis demonstrated that decreased renal function is an independent predictor of 3-year mortality in all five formulas, with risk increasing by 15–25% for each 10-unit decrease in eGFR. Despite the similarities between the formulas, the ability to predict mortality was highest in the Mayo formula and lowest in MDRD.

Conclusions
Our data suggest that while the Mayo formula is not currently recommended by any nephrology guidelines, it may be an alternative formula to predict mortality among patients with multivessel CAD, including to the widely used MDRD formula.
Lung cancer with partial anomalous pulmonary venous connection in a different lobe: a case report
Authors: Watanabe Hikaru , Kanauchi Naoki , Abe Kouhei , Matsuo Soumei 
Published: May 2021

Abstract
Background
Anomalous pulmonary venous connection (APVC) is a congenital malformation in which the pulmonary veins connect to the systemic venous system but not to the left atrium. APVC can be classified as total or partial (PAPVC). PAPVC is rare among surgical patients with lung cancer, and most cases are detected incidentally during surgery. We herein report a patient with lung cancer in whom PAPVC was diagnosed before surgery, which made it difficult to determine the surgical procedure.

Case presentation
A 71-year-old man was followed-up as an outpatient after surgery for renal cell carcinoma. Chest computed tomography showed a 22-mm nodule in the right lower lobe and PAPVC in the right upper lobe. He was diagnosed with lung adenocarcinoma (cT1cN0M0 stage IA3) and scheduled for surgery. Preoperative catheterization showed a pulmonary to systemic flow ratio (Qp/Qs) of 1.64 and mean pulmonary artery pressure (MPAP) of 16 mmHg. Surgical repair of PAPVC is indicated when a patient is symptomatic and has a Qp/Qs ≥1.5–2.0. The patient was scheduled for right lower lobectomy, but postoperative worsening of right heart strain was considered. Concomitant PAPVC repair was therefore considered, but he had no atrial septal defect and was asymptomatic; therefore, PAPVC treatment was considered unnecessary. However, we planned to perform concomitant PAPVC repair if his circulatory dynamics worsened during surgery or if his MPAP exceeded 25 mmHg. His MPAP was 20 mmHg and his circulatory dynamics remained stable, and right lower lobectomy was therefore completed. His postoperative course was favorable. Follow-up catheterization at 6 months showed a Qp/Qs of 1.19 and MPAP of 18 mmHg, with no evidence of increased right heart strain. There was no evidence of right heart failure or recurrence of lung cancer at last follow-up at 18 months after surgery.

Conclusions
We present a case of right lower lung cancer complicated by PAPVC in the right upper lobe. This case suggests that concomitant repair of PAPVC in the right upper lobe may not be necessary when performing right lower lobectomy, although the patient’s Qp/Qs and MPAP should be considered.
Ocular manifestations of ectodermal dysplasia
Authors: Landau Prat Daphna , Katowitz William R. , Strong Alanna , Katowitz James A. 
Published: May 2021

Abstract
Purpose
The ectodermal dysplasias (EDs) constitute a group of disorders characterized by abnormalities in two or more ectodermal derivatives, including skin, hair, teeth, and sweat glands. The purpose of the current study was to evaluate ocular manifestations in pediatric patients with ED.

Methods
Retrospective case series including consecutive ED subjects who were treated in the ophthalmology department at the Children’s Hospital of Philadelphia over a 12-year period (2009–2020). Main Outcome Measures were ocular and ocular adnexal abnormalities.

Results
Thirty subjects were included: 20 males (67%), mean age of 4.5 years (range 0.3–18). Patients with different subtypes were included, with the hypohidrotic ED and ectrodactyly-ectodermal dysplasia-clefting variants being most prevalent. Most common findings were: lacrimal drainage obstruction in 12 (40%) including punctal agenesis in 10 (33%), refractive errors in 13 (43%) and amblyopia in 6 (20%). A new finding of eyelid ptosis or eyelash ptosis was demonstrated in 11 subjects (37%), mostly associated with TP63 or EDA1 genes variants.

Conclusion
Ectodermal dysplasias are associated with various ocular pathologies and amblyopia in the pediatric population. We report a possible genetic association between lash ptosis and EDA1 gene, and eyelid ptosis and TP63 or EDA1 genes variants.
How to design a registry for undiagnosed patients in the framework of rare disease diagnosis: suggestions on software, data set and coding system
Authors: Berger Alexandra , Rustemeier Anne-Kathrin , Göbel Jens , Kadioglu Dennis , Britz Vanessa , Schubert Katharina , Mohnike Klaus , Storf Holger , Wagner Thomas O. F. 
Published: May 2021

AbstractBackgroundAbout 30 million people in the EU and USA, respectively, suffer from a rare disease. Driven by European legislative requirements, national strategies for the improvement of care in rare diseases are being developed. To improve timely and correct diagnosis for patients with rare diseases, the development of a registry for undiagnosed patients was recommended by the German National Action Plan. In this paper we focus on the question on how such a registry for undiagnosed patients can be built and which information it should contain.ResultsTo develop a registry for undiagnosed patients, a software for data acquisition and storage, an appropriate data set and an applicable terminology/classification system for the data collected are needed. We have used the open-source software Open-Source Registry System for Rare Diseases (OSSE) to build the registry for undiagnosed patients. Our data set is based on the minimal data set for rare disease patient registries recommended by the European Rare Disease Registries Platform. We extended this Common Data Set to also include symptoms, clinical findings and other diagnoses. In order to ensure findability, comparability and statistical analysis, symptoms, clinical findings and diagnoses have to be encoded. We evaluated three medical ontologies (SNOMED CT, HPO and LOINC) for their usefulness. With exact matches of 98% of tested medical terms, a mean number of five deposited synonyms, SNOMED CT seemed to fit our needs best. HPO and LOINC provided 73% and 31% of exacts matches of clinical terms respectively. Allowing more generic codes for a defined symptom, with SNOMED CT 99%, with HPO 89% and with LOINC 39% of terms could be encoded.ConclusionsWith the use of the OSSE software and a data set, which, in addition to the Common Data Set, focuses on symptoms and clinical findings, a functioning and meaningful registry for undiagnosed patients can be implemented. The next step is the implementation of the registry in centres for rare diseases. With the help of medical informatics and big data analysis, case similarity analyses could be realized and aid as a decision-support tool enabling diagnosis of some undiagnosed patients.
“Strengthening data quality and reporting from small-scale surveys in humanitarian settings: a case study from Yemen, 2011–2019”
Authors: Ogbu Thomas Jideofor , Guha-Sapir Debarati 
Published: May 2021

Abstract
Background
Under-five death rate is one of the major indicators used in assessing the level of needs and severity of humanitarian crisis. Over the years, a number of small-scale surveys based on Standardized Monitoring and Assessment of Relief and Transitions methodology has been conducted in Yemen, these serve as a guide for policy maker and the humanitarian community. The aim of this study is to identify critical methodological and reporting weaknesses that are easy to correct and would improve substantively the quality of the results.

Methods
We obtained seventy-seven surveys conducted across 22 governorates in Yemen between 2011 and 2019 and divided the analysis period into pre-crisis (2011–2014) and crisis period (2015–2019) for comparison. We analysed survey qualities such as sampling methodology, completeness of reporting of Under-five death rate and mortality sample size for children less than five (children < 5) years old.

Results
Seventy-seven (71.9%) out of 107 surveys met the eligibility criteria to be included in the study. The methodological quality and reporting are as varied as the surveys. 23.4% (n = 18) met the criteria for quality of sampling methodology, while 77.9%(n = 60) presented required information for the estimation of required mortality sample size and 40.3%(n = 31) met the quality check for reporting of Under-five death rate.

Conclusions
Our assessment indicated that there is no strict adherence to the sampling methodology set out in Standardized Monitoring and Assessment of Relief and Transitions guidelines, and reporting of mortality and sample size data. Adherence to methodological guidelines and complete reporting of surveys in humanitarian settings will vastly improve both the quality and uptake of key data on health and nutrition of the affected population.
The safety of Covid-19 mRNA vaccines: a review
Authors: Anand Pratibha , Stahel Vincent P. 
Published: May 2021

AbstractThe novel coronavirus disease 2019 (COVID-19) has infected more than 100 million people globally within the first year of the pandemic. With a death toll surpassing 500,000 in the United States alone, containing the pandemic is predicated on achieving herd immunity on a global scale. This implies that at least 70-80 % of the population must achieve active immunity against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), either as a result of a previous COVID-19 infection or by vaccination against SARS-CoV-2. In December 2020, the first two vaccines were approved by the FDA through emergency use authorization in the United States. These vaccines are based on the mRNA vaccine platform and were developed by Pfizer/BioNTech and Moderna. Published safety and efficacy trials reported high efficacy rates of 94-95 % after two interval doses, in conjunction with limited side effects and a low rate of adverse reactions. The rapid pace of vaccine development and the uncertainty of potential long-term adverse effects raised some level of hesitation against mRNA vaccines in the global community. A successful vaccination campaign is contingent on widespread access to the vaccine under appropriate storage conditions, deployment of a sufficient number of vaccinators, and the willingness of the population to be vaccinated. Thus, it is important to clarify the objective data related to vaccine safety, including known side effects and potential adverse reactions. The present review was designed to provide an update on the current state of science related to the safety and efficacy of SARS-CoV-2 mRNA vaccines.
Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies
Authors: Tian Zheng , Liu Ming , Zhang Ya , Wang Xin 
Published: May 2021

AbstractHarnessing the power of immune cells, especially T cells, to enhance anti-tumor activities has become a promising strategy in clinical management of hematologic malignancies. The emerging bispecific antibodies (BsAbs), which recruit T cells to tumor cells, exemplified by bispecific T cell engagers (BiTEs), have facilitated the development of tumor immunotherapy. Here we discussed the advances and challenges in BiTE therapy developed for the treatment of hematologic malignancies. Blinatumomab, the first BiTE approved for the treatment of acute lymphocytic leukemia (ALL), is appreciated for its high efficacy and safety. Recent studies have focused on improving the efficacy of BiTEs by optimizing treatment regimens and refining the molecular structures of BiTEs. A considerable number of bispecific T cell-recruiting antibodies which are potentially effective in hematologic malignancies have been derived from BiTEs. The elucidation of mechanisms of BiTE action and neonatal techniques used for the construction of BsAbs can improve the treatment of hematological malignancies. This review summarized the features of bispecific T cell-recruiting antibodies for the treatment of hematologic malignancies with special focus on preclinical experiments and clinical studies.
Pyroptosis: a new paradigm of cell death for fighting against cancer
Authors: Tan Yixin , Chen Quanzhu , Li Xiaoling , Zeng Zhaoyang , Xiong Wei , Li Guiyuan , Li Xiayu , Yang Jianbo , Xiang Bo , Yi Mei 
Published: May 2021

Abstract
Background
Unraveling the mystery of cell death is one of the most fundamental progresses of life sciences during the past decades. Regulated cell death (RCD) or programmed cell death (PCD) is not only essential in embryonic development, but also plays an important role in the occurrence and progression of diseases, especially cancers. Escaping of cell death is one of hallmarks of cancer.

Main body
Pyroptosis is an inflammatory cell death usually caused by microbial infection, accompanied by activation of inflammasomes and maturation of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). Gasdermin family proteins are the executors of pyroptosis. Cytotoxic N-terminal of gasdermins generated from caspases or granzymes proteases mediated cleavage of gasdermin proteins oligomerizes and forms pore across cell membrane, leading to release of IL-1β, IL-18. Pyroptosis exerts tumor suppression function and evokes anti-tumor immune responses. Therapeutic regimens, including chemotherapy, radiotherapy, targeted therapy and immune therapy, induce pyroptosis in cancer, which potentiate local and systemic anti-tumor immunity. On the other hand, pyroptosis of normal cells attributes to side effects of anti-cancer therapies.

Conclusion
In this review, we focus on the regulatory mechanisms of pyroptosis and the tumor suppressive function of pyroptosis. We discuss the attribution of pyroptosis in reprogramming tumor microenvironments and restoration of anti-tumor immunity and its potential application in cancer immune therapy.
ROS and TGFβ: from pancreatic tumour growth to metastasis
Authors: Chang Chao-Hui , Pauklin Siim 
Published: May 2021

AbstractTransforming growth factor β (TGFβ) signalling pathway switches between anti-tumorigenic function at early stages of cancer formation and pro-tumorigenic effects at later stages promoting cancer metastasis. A similar contrasting role has been uncovered for reactive oxygen species (ROS) in pancreatic tumorigenesis. Down-regulation of ROS favours premalignant tumour development, while increasing ROS level in pancreatic ductal adenocarcinoma (PDAC) enhances metastasis. Given the functional resemblance, we propose that ROS-mediated processes converge with the spatial and temporal activation of TGFβ signalling and thereby differentially impact early tumour growth versus metastatic dissemination. TGFβ signalling and ROS could extensively orchestrate cellular processes and this concerted function can be utilized by cancer cells to facilitate their malignancy. In this article, we revisit the interplay of canonical and non-canonical TGFβ signalling with ROS throughout pancreatic tumorigenesis and metastasis. We also discuss recent insight that helps to understand their conflicting effects on different stages of tumour development. These considerations open new strategies in cancer therapeutics.
Management of oxygen saturation monitoring in preterm newborns in the NICU: the Italian picture
Authors:   on behalf of the National Study Group of Neonatal Clinical Biochemistry of the Italian Society of Neonatology, Perrone Serafina , Giordano Maurizio , De Bernardo Giuseppe , Lugani Paola , Sarnacchiaro Pasquale , Stazzoni Gemma , Buonocore Giuseppe , Esposito Susanna , Tataranno Maria Luisa 
Published: May 2021

Abstract
Background
Although many studies emphasize the importance of using oxygen saturation (SpO2) targets in the NICUs, there is a wide variability in used saturation ranges among centers. Primary aim was to draw a representative picture on how the management of oxygen monitoring is performed in the Italian NICUs. Second aim was to identify healthcare-professionals related factors associated with oxygen targeting in the preterm population.

Methods
Cross-sectional study with data collection via an electronic survey form. A questionnaire containing pre-piloted and open questions on monitoring and management of the SpO2 was administered to neonatologists across the network of the Italian Society of Neonatology. The questions focused on: the infrastructure, specific training, healthcare professionals and patients-related factors. The results of the survey were anonymously collected, summarized and analyzed.

Results
Out of 378 questionnaires, 93 were correctly filled. Thirty-six different SpO2 ranges were observed. Centers using written standard operating procedures on oxygen management and SpO2 monitoring maintained a correct average range of SpO2 90–95%, avoided hyperoxia and reconsidered saturation targets in relation to comorbidities. 39.8% of responders disabled alarms during neonatal care. One center used biomarkers for complete monitoring of neonatal oxygenation status.

Conclusions
There is considerable variation in SpO2 targets for preterm infants in the Italian NICUs. Standard operating procedures and specific training for health care personnel are the main factors playing a role for the correct maintenance of the recommended oxygen targets in preterms.