bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Tn7-Based Genomic Integration Is Dependent on an attTn7 Box in the glms Gene and Is Site-Specific With Monocopy in Ralstonia solanacearum Species Complex
Authors: Zhang Yong , Cao Yuzhu , Zhang Lichun , Hikichi Yasufumi , Ohnishi Kouhei , Li Jing 
Published: March 2021

The Tn7-based genomic integration system enables direct insertion of foreign gene elements into the chromosome downstream of glms in many bacteria species. The glms gene is greatly conserved in Ralstonia solanacearum species complex (RSSC), while its downstream regions are mostly different in the RSSC. Here, we provided genetic evidence to validate that this Tn7 integration is dependent on a conserved 30-bp motif in the glms, called an attTn7 box, and artificial attTn7 boxes elsewhere are competent for the Tn7 integration, which is further confirmed to be simultaneous downstream of both original and artificial attTn7 boxes, using PCR. With the whole-genome resequencing on 500 Tn7-colonies, the Tn7 integration was confirmed to be site- specific at 25 bp downstream of glms with monocopy as a chromosome of the RSSC. Characteristic of a monocopy in a chromosome enables the Tn7-based complementation to fully restore phenotypes of mutants to those of parent strains that are advantageous rather than those based on plasmids with low-copy numbers. The Tn7-based genomic integration system provides a generally applicable and versatile genetic tool for studies of complementation, pathogenesis, overexpression, and in-vivo promoter activity assays with monocopy in the RSSC. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Creation of a COVID-19 Based Educational Curriculum: A Blueprint for Redesigning Surgical Education During Times of National Crisis
Authors: Zhang Lindsey M. , Symalla Trever , Roggin Kevin K. , Matthews Jeffrey B. , Hussain Mustafa 
Published: March 2021

Objective:
To create a COVID-19 based educational curriculum for surgical residents.

Background Data:
The COVID-19 pandemic has resulted in disruptions to operative volume and clinical education for surgery residents. This has placed a greater importance on didactic education. However, in the face of pandemic-related uncertainty, focusing on a traditional educational curriculum may be a challenge for surgical residents.

Methods:
A dedicated resident educational team was created. This team identified specific surgical resident needs, evaluated institutional resources, created a curriculum and timeline, determined a feasible implementation format, and assessed resident opinions on the impact of the curriculum via anonymous survey.

Results:
A 1-month long COVID-19 based curriculum was developed, which covered (1) advanced critical care and resuscitation techniques pertinent to patients with COVID-19, (2) institutional physician experience in the COVID-units, (3) ethical dilemmas in resource management, (4) triaging of operative cases during the pandemic, and (5) published and ongoing COVID-19-related surgical research. In the postimplementation survey, a majority of residents reported that the curriculum helped improve their ability to take care of patients during the pandemic, provided an opportunity for questions, alleviated anxieties and concerns, and that they preferred the COVID-19 curriculum over traditional surgical topics.

Conclusions:
In the midst of national crisis and significant clinical disruption, real-time adjustments to surgical education can and should occur to address resident needs. The results of our study may serve as a blueprint for implementing rapid change to resident education in the future.
Anterior Cruciate Ligament Tear Following Operative Treatment of Pediatric Tibial Eminence Fractures in a Multicenter Cohort
Authors: O’Donnell Ryan , Bokshan Steven , Brown Kelsey , Aoyama Julien T. , Ganley Theodore J. , Fabricant Peter D. , Patel Neeraj M. , Ellis Henry B. , Green Daniel W. , Kushare Indranil , Lee R. Jay , McKay Scott , Rhodes Jason , Sachleben Brant , Sargent Catherine , Schmale Gregory A. , Yen Yi-Meng , Mistovich R. Justin , Cruz Aristides I. 
Published: March 2021

Background:Postoperative ipsilateral anterior cruciate ligament (ACL) tears after tibial eminence fracture fixation has been previously noted in the literature. This study aims to describe the prevalence of and risk factors for postoperative ACL tears in a cohort of patients operatively treated for tibial eminence fracture.Methods:A retrospective review of children undergoing treatment of a tibial eminence fracture at 10 tertiary care children’s hospitals was performed. The primary outcome of interest was subsequent ACL rupture. Incidence of ACL tear was recorded for the entire cohort. Patients who sustained a postoperative ACL tear were compared with those without ACL tear and analyzed for demographics and risk factors. A subgroup analysis was performed on patients with a minimum of 2-year follow-up data or those who had met the primary outcome (ACL tear) before 2 years.Results:A total of 385 pediatric patients were reviewed. 2.6% of the cohort experienced a subsequent ACL tear. The median follow-up time was 6.5 months (SD=6.4 mo). Subsequent ACL tears occurred at a median of 10.2 months (SD=19.5 mo) postoperatively. There was a statistically significant association with higher grade tibial spine fractures (Myers and McKeever type III and IV) and subsequent ACL tear (P=0.01). Patients with a subsequent ACL tear were older on average (13.5 vs. 12.2 y old), however, this difference was not statistically significant (P=0.08). Subgroup analysis of 46 patients who had a 2-year follow-up or sustained an ACL tear before 2 years showed a 21.7% incidence of a subsequent ACL tear. There was a statistically significant association with higher grade tibial spine fractures (Myers and McKeever type III and IV) and subsequent ACL rupture (P=0.006) in this subgroup. Postoperative ACL tears occurred in patients who were older at the time that they sustained their original tibial eminence fracture (13.4 vs. 11.3 y old,P=0.035).Conclusions:Ipsilateral ACL tears following operatively treated pediatric tibial eminence fractures in a large multicenter cohort occurred at a rate of 2.6%. However, in those with at least 2 years of follow-up, the incidence was 21.7%. Subsequent ACL tear was more likely in those with completely displaced (type III or IV) tibial eminence fractures and older patients.Level of Evidence:Level III—retrospective cohort study.
Prenatal Diagnosis of Dystrophinopathy and Cytogenetic Analysis in 303 Chinese Families
Authors: Li Mengmeng , Hao Na , Yao Fengxia , Zhang Weimin , Zhou Jing , Tan Li , Qiu Zhengqing , Liu Juntao 
Published: March 2021

Abstract

Objective:
This study was to supply information of the Duchenne muscular dystrophy (DMD) mutational spectrum in 303 Chinese families and further offer 5-year clinical experience of DMD/Becker muscular dystrophy genetic counseling and prenatal diagnosis.

Methods:
In this retrospective cohort study, three hundred and five pregnancies in 303 pregnant women who has a birth history of DMD/Becker muscular dystrophy patients underwent prenatal diagnosis using multiplex ligation-dependent probe amplification followed by Sanger sequencing between January 2014 and December 2018 at Peking Union Medical College Hospital. The mean age of pregnant women was (33.0 ± 4.1) years old. Karyotype analysis was performed to exclude fetal abnormal karyotype.

Results:
The detection rate of DMD gene mutation in 303 probands was (296/303) 97.7% with seven families having a negative genetic diagnosis. The mutational spectrum comprised of large arrangements in 288/303 (95.0%) and small mutations in 8/303 (2.6%). Carrier testing was performed among 204 pregnant women among whom, 108 mothers had the same mutation as family proband. Of the 305 pregnancies underwent prenatal diagnosis, 55 of 173 male fetuses were affected. We also performed karyotype analysis and found three abnormal karyotypes of trisomy 21. We even found a fetus with DMD gene mutation and trisomy 21 in a same fetus by further analysis. We also identified two times of germline mosaicism.

Conclusion:
This study demonstrated the distribution and mutation profile of 303 probands and 305 fetuses. Furthermore, considering the possbility of maternl germilne mosaicism, prenatal diagnosis should be suggested to mothers with a proband whether they carry the causative mutation in their blood or not.
Effects of inverted photoperiods on the blood pressure and carotid artery of spontaneously hypertensive rats and Wistar–Kyoto rats
Authors: Wang YunLei , Zhang Tong , Zhang YuGe , Yu Yan , Bai Fan , Zhang HaoJie , Chi YaFei 
Published: March 2021

Objective:
The objective of this study was to investigate the effects of inverted photoperiods on the blood pressure and carotid arteries in spontaneously hypertensive rats (SHRs) and Wistar–Kyoto (WKY) rats (homologous control group).

Methods and results:
This study used two inverted photoperiods [inverted light:dark (ILD)16 : 8 and ILD12 : 12] to create the model. A total of 27 male SHR and 27 male WKY rats were randomly divided into six groups (nine rats per group): SHR (LD12 : 12), SHR (ILD16 : 8), SHR (ILD12 : 12), WKY (LD12 : 12), WKY (ILD16 : 8) and WKY (ILD12 : 12). We recorded the trajectory of the activity rhythm of the rats and performed carotid vascular ultrasound examination, MRI (arterial spin labelling) analysis and carotid biopsy. The results showed that inverted photoperiods increased the blood pressure, carotid intima-media thickness, resistance index and blood flow velocity. In addition, inverted photoperiods led to the development of carotid arterial thrombosis, significantly reduced cerebral blood flow and increased the number of collagen fibres. Moreover, it increased the expression of angiotensin receptor and low-density lipoprotein receptor in the carotid arteries, leading to decreased expression of 3-hydroxy-3-methylglutaryl-Coenzyme A reductase and nitric oxide synthase. Inverted photoperiods induced the formation of atherosclerotic plaque. Multiple results of SHR were worse than those of WKY rats.

Conclusion:
Taken together, inverted photoperiods can produce a series of adverse consequences on blood pressure and carotid arteries. Hypertension can aggravate the adverse effects of inverted photoperiods.
How Frequent Is Switching From an Initial Stimulant Family to the Alternative One in the Clinical Setting?
Authors: Biederman Joseph , DiSalvo Maura , Green Allison , Woodworth K. Yvonne , Law Cecilia , Gabrieli John D.E. , Faraone Stephen V. 
Published: March 2021

Abstract

Purpose/Background
This study aimed to evaluate the frequency of needing to switch the initial treatment of a stimulant to the alternative family in newly referred, medication-naive adults with attention-deficit/hyperactivity disorder (ADHD) initiating treatment with stimulants.

Methods/Procedures
Subjects were 49 unmedicated adults (18–45 years old) with Diagnostic and Statistical Manual of Disorders (Fifth Edition) ADHD who initiated treatment with a stimulant. Before the clinical assessment with an expert clinician, participants completed the Adult Self-Report, Behavior Rating Inventory of Executive Function—Adult Version, Emotional Dysregulation Subscale of the Barkley Current Behavior Scale—Self-report, and Mind Wandering Questionnaire. The rate of switching was examined using information from the electronic medical record for up to three clinical follow-up visits. Comparisons were made between those who did and did not need to switch on baseline demographic and clinical characteristics.

Findings/Results
Sixty-seven percent of ADHD patients were initially prescribed a methylphenidate product, and 33%, an amphetamine product. Forty-one percent of ADHD patients needed to switch from their initially prescribed stimulant family within 90 days of initiating treatment because of poor tolerability. Whereas the rate of switching was significantly higher in those initially prescribed methylphenidate, the rate of patients who required changes in formulation (long- to short-acting and vice versa) or additional antianxiety or antidepressant treatment (“strugglers”) was higher in those taking amphetamine. Switchers were more impaired on the Adult Self-Report Intrusive scale, whereas nonswitchers were more impaired on the Behavior Rating Inventory of Executive Function Inhibit and Task Monitor scales. However, these findings were small and of unclear clinical significance.

Implications/Conclusions
Forty-one percent of medication-naive adults with ADHD initiating stimulant treatment required a switch from the initially prescribed stimulant family to the alternative one because of poor tolerability. Switching could not be adequately predicted by baseline demographic or clinical characteristics. These findings call for improved efforts to help identify predictors of response to stimulant treatment in adults with ADHD to avoid unnecessary delays in identifying a safe and effective treatment for these patients.
Management of immunosuppressants in the era of coronavirus disease-2019
Authors: Manansala Michael , Baughman Robert , Novak Richard , Judson Marc , Sweiss Nadera 
Published: March 2021

Purpose of review
Patients on chronic immunosuppressive treatments at baseline are at increased risk of opportunistic infections. These patients are at especially increased risk of morbidity and mortality during the coronavirus-19 (COVID-19) pandemic. This review will focus on patients with diseases in which immunosuppression is a vital part of the treatment regimen, including those with solid organ transplants, rheumatologic disorders, sarcoidosis, and inflammatory bowel disease (IBD). We will summarize the current knowledge of immunosuppression in these diseases and the risk of contracting COVID-19. Furthermore, we will discuss if immunosuppression increases severity of COVID-19 presentation.

Recent findings
Since the start of the COVID-19 pandemic, a large number patients receiving chronic immunosuppression have been infected with SARS-CoV-2. Moreover, our understanding of the immunology of SARS-CoV-2 is advancing at a rapid pace. Currently, a number of clinical trials are underway to investigate the role of immunosuppressive treatments in the management of this disease.

Summary
Currently, there is no conclusive evidence to suggest that solid organ transplant recipients on chronic immunosuppression are at increased risk of contracting COVID-19. Solid organ transplant recipients may be at increased risk for worse COVID-19 outcomes but the data are not consistent. There is evidence to suggest that patients with rheumatologic disorders or IBDs are not at increased risk of contracting COVID-19 and do not necessarily experience worse clinical outcomes. Patients with sarcoidosis are not necessarily at increased risk of COVID-19, although there is limited data available to determine if immunosuppression worsens outcomes in this population.
The liver in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
Authors: Davidov-Derevynko Yana , Ben Yakov Gil , Wieder Anat , Segal Gad , Naveh Lior , Orlova Natalia , Gringauz Irina , Amit Sharon , Mor Orna , Klempfner Robert , Rahav Galia , Ben Ari Ziv 
Published: March 2021

Background
The ongoing outbreak of COVID-19 is associated with higher levels of morbidity and mortality among patients with comorbidities, including the metabolic syndrome. Liver impairment has been reported in up to 54% of hospitalized patients with COVID-19. The impact of COVID-19 on a preexisting chronic liver disease is an actively studied area of research. The contribution of our study is towards determining the predictors of severity and the outcome of liver injury among hospitalized patients with COVID-19 infection, including patients with a preexisting liver disease and COVID-19.

Methods
This single center retrospective cohort study included all patients ≥18 years, admitted in Sheba Medical Center with confirmed COVID-19 infection. Demographic, clinical and laboratory data were obtained using the MDClone platform and rechecked after data decryption using electronic health records.

Results
Of 382 patients with COVID-19, 66.4% had increased liver biochemistry. Mild increase was observed in 76.7%. The higher level of fibrosis-4 (FIB-4) at admission was independently associated with higher mortality rate. Preexisting liver disease was detected in 15.4% patients. Most common etiology was nonalcoholic fatty liver disease (78.7%). The mortality of hospitalized patients with preexisting liver disease was 16.7% compared to 6.8% in patients without preexisting liver disease (RR = 2.792, P = 0.01). In multivariate analysis, liver disease adjusted to age and BMI was associated with mortality with high statistical significance.

Conclusions
Patients with preexisting chronic liver disease were at a higher risk of mortality. The FIB-4 level at admission was associated with worse prognosis. These findings should be reevaluated in a larger cohort of patients.
The utility of faecal and urine biomarkers for small bowel diseases
Authors: Ismail M.S. , Semenov Serhiy , McNamara Deirdre 
Published: March 2021

Purpose of review
Small bowel diseases pose a unique diagnostic and management challenge and often requires tertiary specialist referral. The use of biomarkers may provide a cheap, noninvasive tool to assess the small bowel in terms of diagnosis, offering a better way to triage referrals and select patients for early management. This review looks at the most recent evidence behind the use of several faecal and urine biomarkers for small bowel diseases.

Recent findings
Faecal calprotectin shows the most promise, with evidence to support its role in predicting relapse postsurgery and monitoring treatment response in patients with Crohn's disease. A faecal calprotectin less than 50 μg/g may also be used as a cut-off to triage further investigation. Faecal lactoferrin also appears promising as a marker of small bowel inflammation. A positive faecal immunohistochemistry test precapsule may help to prioritize referrals for obscure bleeding.

Summary
The use of biomarkers in the diagnosis and management of small bowel disease is still controversial and remains unclear. More studies are required to further develop their potential and before societal guidelines can be developed to direct their appropriate use in clinical practice.
Pediatric Severe Sepsis and Shock in Three Asian Countries: A Retrospective Study of Outcomes in Nine PICUs
Authors: Samransamruajkit Rujipat , Wong Judith Ju-Ming , Smathakane Chutima , Anantasit Nattachai , Sunkonkit Kanokkarn , Ong Jacqueline , Lee Olive Pei Ee , Lee Pei-Chuen , Phumeetham Suwannee , Sultana Rehena , Lapwanich Usa , Lee Jan Hau , Kongkiattikul Lalida 
Published: March 2021

OBJECTIVES:
Pediatric sepsis remains a major health problem and is a leading cause of death and long-term disability worldwide. This study aims to characterize epidemiologic, therapeutic, and outcome features of pediatric severe sepsis and septic shock in three Asian countries.

DESIGN:
A multicenter retrospective study with longitudinal clinical data over 1, 6, 24, 48, and 72 hours of PICU admission. The primary outcome was PICU mortality. Multivariable logistic regression analysis was used to identify factors at PICU admission that were associated with mortality

SETTING:
Nine multidisciplinary PICUs in three Asian countries.

PATIENTS:
Children with severe sepsis or septic shock admitted to the PICU from January to December 2017.

INTERVENTION:
None.

MEASUREMENT AND MAIN RESULTS:
A total of 271 children were included in this study. Median (interquartile range) age was 4.2 years (1.3–10.8 yr). Pneumonia (77/271 [28.4%]) was the most common source of infection. Majority of patients (243/271 [90%]) were resuscitated within the first hour, with fluid bolus (199/271 [73.4%]) or vasopressors (162/271 [59.8%]). Fluid resuscitation commonly took the form of normal saline (147/199 [74.2%]) (20 mL/kg [10–20 mL/kg] over 20 min [15–30 min]). The most common inotrope used was norepinephrine 81 of 162 (50.0%). Overall PICU mortality was 52 of 271 (19.2%). Improved hemodynamic variables (e.g., heart rate, blood pressure, and arterial lactate) were seen in survivors within 6 hours of admission as compared to nonsurvivors. In the multivariable model, admission severity score was associated with PICU mortality.

CONCLUSIONS:
Mortality from pediatric severe sepsis and septic shock remains high in Asia. Consistent with current guidelines, most of the children admitted to these PICUs received fluid therapy and inotropic support as recommended.
Use of Negative Pressure Ventilation in Pediatric Critical Care: Experience in 56 PICUs in the Virtual Pediatric Systems Database (2009–2019)
Authors: Moffitt Cynthia A. , Deakins Kathleen , Cheifetz Ira , Clayton Jason A. , Slain Katherine N. , Shein Steven L. 
Published: March 2021

OBJECTIVES:
Negative pressure ventilation may be more physiologic than positive pressure ventilation, but data describing negative pressure ventilation use in the PICU are limited. We aimed to describe the epidemiology and outcomes of PICU patients receiving negative pressure ventilation.

DESIGN:
Descriptive analysis of a large, quality-controlled multicenter database.

SETTING:
Fifty-six PICUs in the Virtual Pediatric Systems database who reported use of negative pressure ventilation.

PATIENTS:
Children admitted to a participating PICU between 2009 and 2019 who received negative pressure ventilation.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Among 788 subjects, 71% were less than 2 years old, and 45% had underlying health conditions. Two concurrent aspiration events were the only adverse events reported. After excluding one over-represented center, the 3 years with the most negative pressure ventilation usage were 2017–2019 (all > 25 cases/yr and ≥ 13 centers reporting usage). Among those 187 children, the most common primary diagnoses were bronchiolitis and cardiac disease (both 15.5%), 24.1% required endotracheal intubation after negative pressure ventilation, and 9.1% died.

CONCLUSIONS:
Negative pressure ventilation is being used in many PICUs, most commonly for pulmonary infections or cardiac disease, in children with high rates of subsequent intubation and mortality and with few documented adverse events. Use at individual centers is rare but increasing, suggesting need for prospective collaboration to better evaluate the role of negative pressure ventilation in the PICU.
Diagnosis of Posterior Urethral Valves in an Infant Using Point-of-Care Ultrasound
Authors: Gillon Jason T. , Cohen Stephanie G. 
Published: March 2021

Abstract
This case describes a 7-week-old male infant presenting with vomiting and decreased urine output. Initial point-of-care ultrasound (POCUS) demonstrated a normal pylorus; however, assessment of bladder volume revealed the problem. The bladder was distended with a thickened, trabeculated wall and there was bilateral hydroureter, consistent with bladder outlet obstruction. Renal POCUS revealed bilateral hydronephrosis and perinephric fluid collections consistent with calyceal rupture. A voiding cystourethrogram confirmed the diagnosis of posterior urethral valves which were eventually ablated by urology. To our knowledge, this is the first case report of POCUS leading to a diagnosis of posterior urethral valves in an infant. This case highlights how POCUS can expedite evaluation of decreased urine output.