bluuebunny/crossref_metadata_2025_split huggingface dataset:
Downregulation of Odd-Skipped Related 2, a Novel Regulator of Epithelial-Mesenchymal Transition, Enables Efficient Somatic Cell Reprogramming
Authors: Anh Le Phuong Hoang , Nishimura Ken , Kuno Akihiro , Linh Nguyen Thuy , Kato Tetsuo , Ohtaka Manami , Nakanishi Mahito , Sugihara Eiji , Sato Taka-Aki , Hayashi Yohei , Fukuda Aya , Hisatake Koji 
Published: February 2022

Abstract
Somatic cell reprogramming proceeds through a series of events to generate induced pluripotent stem cells (iPSCs). The early stage of reprogramming of mouse embryonic fibroblasts is characterized by rapid cell proliferation and morphological changes, which are accompanied by downregulation of mesenchyme-associated genes. However, the functional relevance of their downregulation to reprogramming remains poorly defined. In this study, we have screened transcriptional regulators that are downregulated immediately upon reprogramming, presumably through direct targeting by reprogramming factors. To test if these transcriptional regulators impact reprogramming when expressed continuously, we generated an expression vector that harbors human cytomegalovirus upstream open reading frame 2 (uORF2), which reduces translation to minimize the detrimental effect of an expressed protein. Screening of transcriptional regulators with this expression vector revealed that downregulation of (odd-skipped related 2 [Osr2]) is crucial for efficient reprogramming. Using a cell-based model for epithelial-mesenchymal transition (EMT), we show that Osr2 is a novel EMT regulator that acts through induction of transforming growth factor-β (TGF-β) signaling. During reprogramming, Osr2 downregulation not only diminishes TGF-β signaling but also allows activation of Wnt signaling, thus promoting mesenchymal-epithelial transition (MET) toward acquisition of pluripotency. Our results illuminate the functional significance of Osr2 downregulation in erasing the mesenchymal phenotype at an early stage of somatic cell reprogramming.
For Subacute Pain After Surgically Managed Fractures, Strong Opioids Not Superior to Mild Opioids
Authors: Rosenberg Karen 
Published: February 2022

According to this study:

In patients with surgically managed orthopedic fractures, treatment with strong opioid medication isn't superior to treatment with milder opioid medication for the management of postdischarge pain.Ongoing use of strong opioids after hospital discharge shouldn't be supported.
Efficacy Comparison of 3 Kinds of Distal Tibial Hemiepiphyseal Implants in the Treatment of Postoperative Ankle Valgus of Congenital Pseudarthrosis of the Tibia
Authors: Hu Xiongke , Li Anping , Liu Kun , Mei Haibo 
Published: February 2022

Background:
Congenital pseudarthrosis of the tibia (CPT) is a complex and serious disease in orthopaedics which often requires multiple operations for treatment. Postoperative ankle valgus deformity is easily seen after the operation of CPT. The aim of this study is to retrospectively evaluate the effectiveness of three different implants for treating postoperative ankle valgus after CPT.

Methods:
A total of 41 patients with postoperative ankle valgus after CPT from December 2010 to July 2019 were selected. Of these 41 patients, 23 patients were treated with “U”-shaped staple, 10 patients were treated with hollow screw and 8 patients were treated with cortical bone screw. The evaluation index was tibiotalar angle. The general data, preoperative, postoperative, and final follow-up imaging data were recorded, and the deformity correction rate and complications were compared.

Results:
All the patients were performed with postoperative follow-up visit for at least 12 months (31 mo on average). In the “U”-shaped staple group, the preoperative tibiotalar angle was 74.8±4.8 degrees, the tibiotalar angle was 85.8±4.5 degrees when the internal fixation was removed; in the hollow screw group, the average preoperative tibiotalar angle was 72.2±6.1 degrees, the average tibiotalar angle was 88.4±5.1 degrees when the internal fixation was removed; in the cortical bone screw group, the average preoperative tibiotalar angle was 75.1±4.2 degrees, the average tibiotalar angle was 88.4±5.1 degrees when the internal fixation was removed. The correction rate of the “U”-shaped staple group was 0.71 degrees/month, with that of in the hollow screw group and cortical bone screw group being 0.64 degrees/month and 0.61 degrees/month, respectively. There was no significant difference in the correction rate between the 3 groups. One case of internal fixation complication was reported in the hollow screw group; 2 cases of missing correction effect were reported, 1 in cortical bone screw group and 1 in hollow screw group; and 2 cases showing symptom of wound pain were reported in the “U”-shaped staple group.

Conclusion:
Ankle valgus is a common postoperative complication of congenital tibial pseudarthrosis. Temporary hemiepiphysiodesis with “U”-shaped staple or screws is an effective treatment for postoperative ankle valgus deformity of CPT in children.

Level of Evidence:
Level IV—retrospective study.
Establishment and Evaluation of a Prediction Model of BLR for Severity in Coronavirus Disease 2019
Authors: He Zebao , Rui Fajuan , Yang Hongli , Ge Zhengming , Huang Rui , Ying Lingjun , Zhao Haihong , Wu Chao , Li Jie 
Published: February 2022

Abstract

Background:
Coronavirus disease 2019 (COVID-19) is an emerging infectious disease and has spread worldwide. Clinical risk factors associated with the severity in COVID-19 patients have not yet been well delineated. The aim of this study was to explore the risk factors related with the progression of severe COVID-19 and establish a prediction model for severity in COVID-19 patients.

Methods:
We retrospectively recruited patients with confirmed COVID-19 admitted in Enze Hospital, Taizhou Enze Medical Center (Group) and Nanjing Drum Tower Hospital between January 24 and March 12, 2020. Take the Taizhou cohort as the training set and the Nanjing cohort as the validation set. Severe case was defined based on the World Health Organization Interim Guidance Report criteria for severe pneumonia. The patients were divided into severe and non-severe groups. Epidemiological, laboratory, clinical, and imaging data were recorded with data collection forms from the electronic medical record. The predictive model of severe COVID-19 was constructed, and the efficacy of the predictive model in predicting the risk of severe COVID-19 was analyzed by the receiver operating characteristic curve (ROC).

Results:
A total of 402 COVID-19 patients were included in the study, including 98 patients in the training set (Nanjing cohort) and 304 patients in the validation set (Nanjing cohort). There were 54 cases (13.43%) in severe group and 348 cases (86.57%) in non-severe group. Logistic regression analysis showed that body mass index (BMI) and lymphocyte count were independent risk factors for severe COVID-19 (all P
< 0.05). Logistic regression equation based on risk factors was established as follows: Logit (BL)=–5.552–5.473 ×
L + 0.418 × BMI. The area under the ROC curve (AUC) of the training set and the validation set were 0.928 and 0.848, respectively (all P
< 0.001). The model was simplified to get a new model (BMI and lymphocyte count ratio, BLR) for predicting severe COVID-19 patients, and the AUC in the training set and validation set were 0.926 and 0.828, respectively (all P < 0.001).

Conclusions:
Higher BMI and lower lymphocyte count are critical factors associated with severity of COVID-19 patients. The simplified BLR model has a good predictive value for the severe COVID-19 patients. Metabolic factors involved in the development of COVID-19 need to be further investigated.
Human IFN-κ Inhibited Respiratory RNA Virus Replication Dependent on Cell-to-Cell Interaction in the Early Phase
Authors: Fu Weihui , Sun Peng , Fan Jun , Ding Longfei , Yuan Songhua , Zhai Guanxing , Zhang Miaomiao , Qiu Chenli , Zhang Shuye , Zhang Xiaoyan , Xu Jianqing 
Published: February 2022

Abstract

Background:
Interferon kappa (IFN-κ) is a type I interferon (IFN-I) that inhibits virus replication by evoking interferon-stimulated genes (ISGs). However, as an evolutionarily ancient interferon, IFN-κ may function differently from the later emerged interferon-α and β.

Methods:
Conventional molecular biology methods were used to determine the localization of IFN-κ and its structure and function. In addition, we employed RT-PCR, western blot, and RNA-Seq technologies to characterize the ISGs expression profile and antiviral activities exerted by IFN-κ or IFN-α2.

Results:
Human IFN-κ exists in two forms upon ectopic expression, one located on the cell membrane and the other secreted outside the cells. The membrane-anchored IFN-κ showed the ability to induce ISGs and curtail RNA virus replication, whereas the secreted IFN-κ failed to do so. Structural analyses indicated that 1-27aa at the N-terminus was the signal peptide, and 28-37aa was predicted as the transmembrane region. However, our data demonstrated that both of them were not associated with membrane localization of IFN-κ; the former influenced the expression and secretion of IFN-κ, and the latter had an impact on the induction of ISGs. In addition, prokaryotic purified soluble mature human IFN-κ was also capable of inducing ISGs and inhibiting RNA virus replication. Importantly, human IFN-κ induced a faster ISG response but with a lower intensity and a shorter half-life than the response of IFN-α2. In contrast, IFN-α2 started to function later but was stronger and more durable than IFN-κ.

Conclusions:
Human IFN-κ-induced ISG response and inhibited respiratory RNA virus replication dependent on cell-to-cell interactions. In addition, compared with IFN-α2, IFN-κ exerted effects more rapidly in the early phase, with less intensity and a shorter half-life. Therefore, IFN-κ may constitute the first line of IFN-I against respiratory virus infections.
From Discovery to Cure, A Great Journey of the Hepatitis C Virus Study
Authors: Yi Zhigang , Yuan Zhenghong 
Published: February 2022

Abstract
Hepatitis C virus (HCV) causes chronic infection in over 75% of the HCV-infected individuals, resulting in liver cancer in substantial patients. Since its discovery in 1989, HCV experiences a journey from discovery to cure, largely due to the virology studies and success of direct antiviral agent (DAA) development. We reviewed the HCV research journey, from the discovery of this virus to the development of DAAs for cure. Learning the methodology used in HCV studies and the knowledge of developing DAAs against HCV may inspire the studies of other difficult-to-culture viruses, such as hepatitis E virus and norovirus, as well as the development of DAAs for other single-stranded positive-sense RNA viruses, including the pandemic-causing SARS-CoV-2 virus, which shares the common replication strategy of forming a membrane-bound viral replicase.
Preterm birth and human milk proteome: are we ready for individualized fortification?
Authors: Zhu Jing , Liu Mengyuan , Xing Yan 
Published: February 2022

Purpose of review
Preterm birth is one of the most pressing clinical problems in obstetrics and neonatology worldwide. One of the most sophisticated components of human milk is the proteome and a better understanding of it can lead to precision guides for feeding preterm infants. In this review, we will examine recent research focused on the human milk proteome and individualized protein fortification of human milk.

Recent findings
In both preterm and term birth, the protein content in mother's own milk dropped rapidly in the early postnatal period. Preterm milk had a higher protein content and contained different protein and endogenous peptide compositions compared with term milk. The peptides in gastrointestinal fluids of preterm infants still need further investigation. Individualized fortification is more superior to standard fortification, but it only focuses on the total protein amount. There is no data concerning the composition and posttranslational modifications of proteins and endogenous peptides with fortification and their longterm effects.

Summary
Comprehensive identification and characterization of the human milk proteome have led to the targeted breast milk fortification theory of preterm infant feeding and has also been enriched by clinical trials. However, to achieve fortification of key proteins and/or endogenous peptides, as standard clinical practice, requires additional studies. Future research should explore the long-term effect of protein fortification and pay more attention to quality rather than quantity in relation to infant body composition and growth outcomes.
Gastrointestinal coronavirus disease 2019 manifestations in childhood
Authors: Sansotta Naire , Norsa Lorenzo , D’Antiga Lorenzo 
Published: February 2022

Purpose of the review
The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged and caused a massive global health crisis. The aim of this review is first, to provide the latest evidence on what is known about the pathophysiology and the transmission of SARS-CoV-2 and then to focus on the manifestations of the gastrointestinal (GI) tract in children with COVID-19. Lastly, we summarise the impact of COVID-19 on patients with preexisting GI diseases.

Recent findings
Even though the virus is mostly transmitted from human to human via respiratory droplets, ACE2 is known to be expressed throughout the GI tract, and SARS-CoV-2 ribonucleic acid has been isolated from patients’ stools. GI symptoms including abdominal pain, diarrhoea and vomiting are frequently reported in paediatric patients. Interestingly, a small number of patients seem to exhibit solely GI symptoms. In addition, a multisystem inflammatory syndrome in children (MIS-C) related to SARS-COV-2 described in children, has a high rate of GI involvement. Several etiopathogenetic mechanisms have been postulated to explain the GI involvement of COVID-19.

Summary
Clinicians should not underestimate or disregard these early or mild GI symptoms, because the patients may be infected and transmit the virus, or develop a more severe condition such as MIS-C.
COVID-19: vaccines, efficacy and effects on variants
Authors: Rudan Igor , Adeloye Davies , Sheikh Aziz 
Published: February 2022

Purpose of review
We reviewed three leading strategies of vaccine development against coronavirus disease 2019 (COVID- 19): mRNA vaccines, adenoviral vector vaccines and recombinant nanoparticles. We also considered the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and their impact on the effectiveness of the most widely implemented vaccines.

Recent findings
General properties, efficacy, safety and global uptake of Pfizer/BioNTech's Comirnaty (BNT162b2), Moderna's Spikevax (mRNA-1273), Oxford/AstraZeneca's ChAdOx1 nCoV-19, J&J/Janssen's Ad26.COV2.S and Novavax's NVX-CoV2373 vaccines at the end of the year 2021 were presented. We summarized the information on the effectiveness against COVID-19 infection, severe disease and death. We then focused on important missense mutations in the five variants of concern (VoC): Alpha, Beta, Gamma, Delta and Omicron. We explored the evidence for the effectiveness of the vaccines against those five VoC.

Summary
It is difficult to predict the further development of the COVID-19 pandemic. The development of vaccines of an increasingly broad spectrum against coronaviruses, more easily deliverable and conferring more durable immune protection is likely. However, the very large number of infections may lead to new mutations with unpredictable impacts. Interventions that would control COVID-19 more effectively and enable a safer coexistence with the SARS-CoV-2 virus and its emerging variants are still needed in early 2022.
Characterization of Inhaled Nitric Oxide Use for Cardiac Indications in Pediatric Patients*
Authors: Yates Andrew R. , Berger John T. , Reeder Ron W. , Banks Russell , Mourani Peter M. , Berg Robert A. , Carcillo Joseph A. , Carpenter Todd , Hall Mark W. , Meert Kathleen L. , McQuillen Patrick S. , Pollack Murray M. , Sapru Anil , Notterman Daniel A. , Holubkov Richard , Dean J. Michael , Wessel David L. ,   on behalf of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network
Published: February 2022

OBJECTIVES:
Characterize the use of inhaled nitric oxide (iNO) for pediatric cardiac patients and assess the relationship between patient characteristics before iNO initiation and outcomes following cardiac surgery.

DESIGN:
Observational cohort study.

SETTING:
PICU and cardiac ICUs in seven Collaborative Pediatric Critical Care Research Network hospitals.

PATIENTS:
Consecutive patients, less than 18 years old, mechanically ventilated before or within 24 hours of iNO initiation. iNO was started for a cardiac indication and excluded newborns with congenital diaphragmatic hernia, meconium aspiration syndrome, and persistent pulmonary hypertension, or when iNO started at an outside institution.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Four-hundred seven patients with iNO initiation based on cardiac dysfunction. Cardiac dysfunction patients were administered iNO for a median of 4 days (2–7 d). There was significant morbidity with 51 of 407 (13%) requiring extracorporeal membrane oxygenation and 27 of 407 (7%) requiring renal replacement therapy after iNO initiation, and a 28-day mortality of 46 of 407 (11%). Of the 366 (90%) survivors, 64 of 366 patients (17%) had new morbidity as assessed by Functional Status Scale. Among the postoperative cardiac surgical group (n = 301), 37 of 301 (12%) had a superior cavopulmonary connection and nine of 301 (3%) had a Fontan procedure. Based on echocardiographic variables prior to iNO (n = 160) in the postoperative surgical group, right ventricle dysfunction was associated with 28-day and hospital mortalities (both, p < 0.001) and ventilator-free days (p = 0.003); tricuspid valve regurgitation was only associated with ventilator-free days (p < 0.001), whereas pulmonary hypertension was not associated with mortality or ventilator-free days.

CONCLUSIONS:
Pediatric patients in whom iNO was initiated for a cardiac indication had a high mortality rate and significant morbidity. Right ventricular dysfunction, but not the presence of pulmonary hypertension on echocardiogram, was associated with ventilator-free days and mortality.
A safe protocol to identify low risk patients with COVID-19 pneumonia for outpatient management
Authors: Teigell Muñoz Francisco Javier , García-Guijarro Elena , García-Domingo Paula , Pérez-Nieto Guadalupe , Rojas Fernando Roque , García-Peña María , Nieto Gallo María Antonia , Melero Bermejo Jose Antonio , de Guzman García-Monge Maria Teresa , Granizo Juan José 
Published: February 2022

ABSTRACTBackgroundThe coronavirus disease 2019 (COVID-19) outbreak has made necessary to rationalize health-care resources, but there are no published data to this moment regarding ambulatory management of patients with COVID-19 pneumonia.ObjectiveEvaluate the results of a protocol for ambulatory management of patients with COVID-19 pneumonia according to the rate of readmissions, admission into the Intensive Care Unit (ICU) and deaths. Identify unfavorable prognostic factors that increase the risk of readmission, ICU admission and/or death.MethodsProspective cohort study of patients with COVID-19 pneumonia discharged from the emergency ward of Infanta Cristina Hospital (Madrid, Spain), that met the criteria of the hospital protocol for outpatient management. We describe outcomes of those patients and compare those who needed readmission versus those we did not. We use logistic regression to explore factors associated with readmissions.Findings314 patients were included, of which 20 (6.4%) needed readmission, 3 (1%) developed severe respiratory failure, and none needed ICU admission nor died. 29.9% of patients had any one comorbidity. Hypertension, leukopenia, lymphocytopenia, increased lactate dehydrogenase (LDH), increased aminotransferases were associated to a higher risk of readmission. A clinical course of 10 days or longer, and an absolute eosinophil count over 200/µL were associated with a lower risk. After multivariate analysis, only hypertension (OR 4.99, CI 1.54-16.02), temperature over 38°C in the emergency ward (OR 9.03, CI: 1.89-45.77), leukopenia (OR 4.92, CI 1.42-17.11) and increased LDH (OR 6.62, CI 2.82-19.26) remained significantly associated to readmission.ConclusionOutpatient management of patients with low-risk COVID-19 pneumonia is safe, if adequately selected. The protocol presented here has allowed avoiding 30% of the admissions for COVID-19 pneumonia in our hospital, with a very low readmission rate and non-existing mortality.FundingThe authors received no specific funding for this work.
Distinguishing Admissions Specifically for COVID-19 from Incidental
SARS-CoV-2 Admissions: A National EHR Research Consortium Study
Authors: Klann Jeffrey G , Strasser Zachary H , Hutch Meghan R , Kennedy Chris J , Marwaha Jayson S , Morris Michele , Samayamuthu Malarkodi Jebathilagam , Pfaff Ashley C , Estiri Hossein , South Andrew M , Weber Griffin M , Yuan William , Avillach Paul , Wagholikar Kavishwar B , Luo Yuan ,   The Consortium for
                    Clinical Characterization of COVID-19 by EHR (4CE), Omenn Gilbert S , Visweswaran Shyam , Holmes John H , Xia Zongqi , Brat Gabriel A , Murphy Shawn N 
Published: February 2022

Abstract
Admissions are generally classified as COVID-19 hospitalizations if the
patient has a positive SARS-CoV-2 polymerase chain reaction (PCR) test. However,
because 35% of SARS-CoV-2 infections are asymptomatic, patients admitted for
unrelated indications with an incidentally positive test could be misclassified
as a COVID-19 hospitalization. EHR-based studies have been unable to distinguish
between a hospitalization specifically for COVID-19 versus an incidental
SARS-CoV-2 hospitalization. From a retrospective EHR-based cohort in four US
healthcare systems, a random sample of 1,123 SARS-CoV-2 PCR-positive patients
hospitalized between 3/2020–8/2021 was manually chart-reviewed and classified as
admitted-with-COVID-19 (incidental) vs. specifically admitted for COVID-19
(for-COVID-19). EHR-based phenotyped feature sets filtered out incidental
admissions, which occurred in 26%. The top site-specific feature sets had 79-99%
specificity with 62-75% sensitivity, while the best performing across-site
feature set had 71-94% specificity with 69-81% sensitivity. A large proportion
of SARS-CoV-2 PCR-positive admissions were incidental. Straightforward EHR-based
phenotypes differentiated admissions, which is important to assure accurate
public health reporting and research.
LABELLING HUMAN KINEMATICS DATA USING CLASSIFICATION MODELS
Authors: Shi Yuan , Chadderwala Nihir , Ratan Ujjwal 
Published: February 2022

AbstractThe goal of this study is to develop a classification model that can accurately and efficiently label human kinematics data. Kinematics data provides information about the movement of individuals by placing sensors on the human body and tracking their velocity, acceleration and position in three dimensions. These data points are available in C3D format that contains numerical data transformed from 3D data captured from the sensors. The data points can be used to analyse movements of injured patients or patients with physical disorders. To get an accurate view of the movements, the datasets generated by the sensors need to be properly labelled. Due to inconsistencies in the data capture process, there are instances where the markers have missing data or missing labels. The missing labels are a hindrance in motion analysis as it introduces noise and produces incomplete datapoints of sensor’s positioning in 3 dimensional space. Labelling the data manually introduces substantial effort in the analysis process. In this paper, we will describe approaches to pre-process the kinematics data from its raw format and label the data points with missing markers using classification models.