bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth and Pubertal Timing in Boys With Adult‐diagnosed Celiac Disease
Authors: Mårild Karl , Ohlsson Claes , Bygdell Maria , Martikainen Jari , Sävendahl Lars , Størdal Ketil , Kindblom Jenny M.
Published: March 2020

There are few longitudinal data on whether childhood growth and pubertal timing may be impaired by adult‐diagnosed celiac disease (CD). Through school health care records and national registers, we retrieved serial growth measurements on 37,672 Swedish boys born in 1945 to 1961, out of whom 72 (0.2%) were clinically diagnosed with CD as adults. Boys with, versus without, adult‐diagnosed CD exhibited no appreciable mean differences in body mass index (BMI, kg/m2) and height (cm) at ages 8 or 20 to 21 years (childhood BMI, 15.9 [CD] vs 15.7 [comparators]; childhood height, 129.1 [CD] vs 128.6 [comparators]; adult BMI, 21.3 [CD] vs 21.4 [comparators]; adult height, 180.7 [CD] vs 180.4 [comparators]). Neither did we observe any between‐group differences in growth development during puberty nor in the timing of pubertal growth spurt (all P values ≥0.30). Conclusively, in this population‐based longitudinal study, boys with adult‐diagnosed CD had similar growth and pubertal timing as their peers.
Caustic Ingestion in Children
Authors: Di Nardo Giovanni , Betalli Pietro , Illiceto Maria Teresa , Giulia Giannotti , Martemucci Luigi , Caruso Flora , Lisi Gabriele , Romano Giusy , Villa Maria Pia , Ziparo Chiara , Pensabene Licia , Vassallo Francesca , Quitadamo Paolo
Published: March 2020

Objectives:

Despite the efforts to reduce the exposure to corrosive household products, caustic ingestion in children is currently a significant medical problem. The aims of the present study were to evaluate the clinical consequences of caustic ingestion and to identify prognostic factors that could concur in driving both diagnostic and therapeutic management.

Methods:

All consecutive children referred for ingestion of a caustic substance from June 2017 to June 2018 were enrolled. Medical records, laboratory and endoscopic findings were reviewed and analyzed.

Results:

We enrolled 44 children with caustic ingestion. Alkaline agents were ingested by 26 of 44 (59.1%) patients, whereas acid agents were ingested by 18 of 44 patients (40.9%). Alkaline rather than acid agents were associated with a worse endoscopic score (r: 0.45) and a higher probability of early esophageal stricture occurrence (r: 0.38). The specific risk of the presence of severe esophageal lesions rose progressively with increasing number of symptoms whereas no esophageal injury was found in asymptomatic patients.

Conclusions:

Our data suggest that endoscopic evaluation is mandatory in symptomatic patients to direct therapeutic management, but it could be avoided in asymptomatic patients after accidental ingestion, particularly if the ingestion is only suspected and patients have no oropharyngeal burns.
Admission Characteristics Identify Risk of Pediatric Acute‐on‐Chronic Liver Failure
Authors: Banc‐Husu Anna M. , Neighbors Katie , Rychlik Karen , Mohammad Saeed , Harris Zena Leah , Alonso Estella M.
Published: March 2020

Objectives:

Acute‐on‐chronic liver failure (ACLF) is well‐studied in adults and characterized by decompensated cirrhosis, multi‐organ failure, and early mortality. Studies of ACLF in children are limited. We sought to characterize the prevalence and clinical factors associated with pediatric ACLF (PACLF).

Methods:

A retrospective review of children 3 months to 18 years listed for liver transplantation and hospitalized for decompensated cirrhosis between January 2007 and December 2017 at a single pediatric hospital. Primary outcome was the development of PACLF, characterized as failure of at least 1 extrahepatic organ (mechanical ventilation, renal replacement therapy, vasoactive medications, grade III/IV hepatic encephalopathy). Characteristics were recorded for each hospitalization.

Results:

Sixty‐six patients had 186 hospitalizations with mean age at admission 4.0 ± 5.6 years and diagnosis of biliary atresia (BA) in 65%. PACLF developed in 20 patients during 23 hospitalizations (12%) and respiratory failure was most common (17/23, 74%). Duration of intensive care unit stay, 13.1 ± 1.2 days versus 0.6 ± 0.6 days (P < 0.001) and length of stay, 24.3 ± 5.0 days versus 7.9 ± 1.9 days (P = 0.003) were longer in PACLF compared with non‐PACLF. Mortality during PACLF hospitalizations was 22%. Clinical factors associated with PACLF were reported from a generalized linear mixed model and included increased admission creatinine (P < 0.0001), increased aspartate aminotransferase (AST) (P = 0.014), increased international normalized ration (INR) (P = 0.0015), and a positive blood culture (P = 0.007).

Conclusion:

In this pediatric series, PACLF developed in 12% of hospitalizations and mortality was high. Admission creatinine, AST, INR, and presence of a positive blood culture were associated with PACLF development.
New vaccine candidates as a scientific solution against the dream of tuberculosis vaccine
Authors: Najafi Azar , Mahdian Nahid , Yousefi Bahman , Karbalaei Mohsen , kermanjani Ali , Ezatpour Behrouz , Eslami Majid
Published: March 2020

Tuberculosis (TB) is accounted for as one of the most important destructive infectious diseases for humans, which is caused by Mycobacterium tuberculosis. Studies have shown the severe effects of tuberculosis in patients, especially sensitive groups. Emergence and distribution of both multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains have caused failure in the infection eradication. At present, BCG vaccine is the only most effective vaccine for the prevention of TB in childhood but its protection level in pulmonary TB in adult is very variable. Therefore, the need for an appropriate alternative vaccine instead of BCG is urgent. On the basis of the studies, cell-mediated immune (CMI) is known as the best immune response against TB infection. For this purpose, a desirable CMI response should be along with a balance between Th1, Th17, and T-reg cells. Several vaccine candidates have been evaluated in vitro and in vivo examinations, such as recombinant BCG (rBCG), DNA vaccines, and subunit vaccines. Factors, such as applicability of vaccine candidates in all individuals, cost-effectiveness, long-term immunity and stimulation of a wide range of responses are important factors. Now, most of these vaccines have entered in the phases of clinical trial (even IIB and III); however, these trials are complex, need a large number of individuals and need a long time. Funding for TB vaccine trials is an important issue, especially in poor countries. With preclinical safety precision studies, it is likely that at least one of these vaccines will develop into early clinical trials in the next few years.
Occupational Exposure in Health Care Personnel to Antineoplastic Drugs and Initiation of Safe Handling in Hong Kong
Authors: Yu Emily
Published: March 2020

Despite the benefits for patients as cancer treatment, antineoplastic drugs may cause adverse effects not only in patients but also in health care personnel. Apart from minor symptoms, antineoplastic agents can cause serious health problems. However, protection from occupational exposures to antineoplastic drugs varies between pharmacy staff and nurses. While protection used for pharmacy staff are more advanced, personal protective equipment seems to be the only protection for most nurses around the world. Exposure can never be totally prevented, but it should be minimized at all costs. Guidelines and recommendations have been published; however, these guidelines do not have legal enforcement power. This article aims to provide a literature review on the occupational exposure of health care personnel to antineoplastic drugs and to reflect the current status in Hong Kong.
Parental Understanding of Research Consent Forms in the PICU: A Pilot Study*
Authors: Gertsman Shira , O’Hearn Katharine , Gibson Jess , Menon Kusum
Published: March 2020

Objectives:

To describe legal guardians’ understanding of key concepts in a research consent form presented within 24 hours of their child’s admission to the PICU and to explore legal guardians’ opinions of the format (language, length) of the consent form and the overall consent process.

Design:

Single-center, exploratory pilot study.

Setting:

PICU at a tertiary-care hospital in Canada.

Subjects:

Forty-one English- and French-speaking legal guardians of children less than 18 years old, who had been admitted to the PICU within the past 24 hours and were expected to stay at least 48 hours, between October 2018 and February 2019.

Interventions:

The consent form from a previous PICU trial was given and explained to legal guardians within 24 hours of their child’s admission to the PICU.

Measurements and Main Results:

Legal guardians’ understanding of key concepts in the consent form was evaluated using a questionnaire the day after the form was explained, and opinions were collected verbally and using an additional survey. The median number of questions answered incorrectly was three of seven (interquartile range = 2–4). Participants best understood the topic of the study (5% incorrect), but 80% of participants were unable to recall a single risk. The median rating of the language in the form was five of five (very easy to understand; interquartile range = 4–5), and 88% of participants said it was a reasonable length.

Conclusions:

Despite positive opinions of the consent form, most legal guardians did not understand all key components of the consent information provided to them orally and in writing within 24 hours of their child’s PICU admission. Future studies are required to determine barriers to understanding and explore alternative approaches to obtaining consent in this setting.
Pediatric Readiness in the Emergency Department and Its Association With Patient Outcomes in Critical Care: A Prospective Cohort Study
Authors: Balmaks Reinis , Whitfill Travis M. , Ziemele Baiba , Blumberga Madara , Upenieks Reinis , Vegeris Ivars , Grope Ilze , Pavare Jana , Auerbach Marc A. , Gross Isabel T.
Published: March 2020

Objectives:

Pediatric mortality in Latvia remains one of the highest among Europe. The purpose of this study was to assess the quality of pediatric acute care and pediatric readiness and determine their association with patient outcomes using a patient registry.

Design:

This was a prospective cohort study. Pediatric readiness was measured using the weighted pediatric readiness score based on a 100-point scale. The processes of care were measured using in situ simulations to generate a composite quality score. Clinical outcome data—including PICU and hospital length of stay as well as 6-month mortality—were collected from the Pediatric Intensive Care Audit Network registry. The associations between composite quality score and weighted pediatric readiness score on patient outcomes were explored with mixed-effects regressions.

Setting:

This study was conducted in all Latvian Emergency Departments and in the national PICU.

Patients:

All patients who were transferred into the national PICU were included.

Interventions:

None.

Measurements and Main Results:

All (16/16) Latvian Emergency Departments participated with a mean composite quality score of 35.3 of 100 and a median weighted pediatric readiness score of 31 of 100. A total of 254 patients were included in the study and followed up for a mean of 436 days, of which nine died (3.5%). Higher weighted pediatric readiness score was associated significantly with lower length of stay in both the PICU and hospital (adjusted ß, –0.06; p = 0.021 and –0.36; p = 0.011, respectively) and lower 6-month mortality (adjusted odds ratio, 0.93; 95% CI, 0.88–0.98).

Conclusions:

These data provide a national assessment of pediatric emergency care in a European country. Pediatric readiness in the emergency department was associated with patient outcomes in this population of pediatric patients transferred to the national PICU.
Respiratory Variations in Aortic Blood Flow to Predict Volume Responsiveness in Ventilated Children With Leukemia and Neutropenic Septic Shock*
Authors: Sun Sijuan , Ren Hong , Wang Ying , Zhang Jian , Li Biru , Ning Botao , Qian Juan
Published: March 2020

Objectives:

To investigate whether respiratory variations in aortic blood flow by echocardiography can accurately predict volume responsiveness in ventilated children with leukemia and neutropenic septic shock.

Design:

A prospective study.

Setting:

A 25-bed PICU of a tertiary hospital.

Patients:

Mechanically ventilated children with leukemia who had been exposed to anthracyclines and exhibited neutropenic septic shock were enrolled.

Interventions:

Transthoracic echocardiography was performed to monitor the aortic blood flow before and after fluid administration.

Measurements and Main Results:

After volume expansion, left ventricular stroke volume increased by greater than or equal to 15% in 16 patients (responders) and less than 15% in 14 patients (nonresponders). The performance of respiratory variation in velocity time integral of aortic blood flow and respiratory variation in peak velocity of aortic blood flow for predicting volume responsiveness, as determined by the area under the receiver operating characteristic curve, was 0.74 (95% CI, 0.55–0.94;p= 0.025) and 0.71 (95% CI, 0.53–0.90;p= 0.048), respectively. Positive end-expiratory pressure was higher in nonresponders than in responders (p= 0.035).

Conclusions:

Respiratory variation in velocity time integral of aortic blood flow and respiratory variation in peak velocity of aortic blood flow derived from transthoracic echocardiography showed only a fair reliability in predicting volume responsiveness in ventilated children with leukemia and neutropenic septic shock.
A Quality Improvement Intervention Bundle to Reduce 30-Day Pediatric Readmissions
Authors: deJong Neal A. , Kimple Kelly S. , Morreale Madlyn C. , Hang Shona , Davis Darragh , Steiner Michael J.
Published: March 2020

Introduction:

Pediatric hospital readmissions can represent gaps in care quality between discharge and follow-up, including social factors not typically addressed by hospitals. This study aimed to reduce the 30-day pediatric readmission rate on 2 general pediatric services through an intervention to enhance care spanning the hospital stay, discharge, and follow-up process.

Methods:

A multidisciplinary team developed an intervention bundle based on a needs assessment and evidence-based models of transitional care. The intervention included pre-discharge planning with a transition coordinator, screening and intervention for adverse social determinants of health (SDH), medication reconciliation after discharge, communication with the primary care provider, access to a hospital-based transition clinic, and access to a 24-hour direct telephone line staffed by hospital attending pediatricians. These were implemented sequentially from October 2013 to February 2017. The primary outcome was the readmission rate within 30 days of index discharge. The length of stay was a balancing measure.

Results:

During the intervention, the included services discharged 4,853 children. The pre-implementation readmission rate of 10.3% declined to 7.4% and remained stable during a 4-month post-intervention observation period. Among 1,394 families screened for adverse SDH, 48% reported and received assistance with ≥ 1 concern. The length of stay increased from 4.10 days in 2013 to 4.30 days in 2017.

Conclusions:

An intervention bundle, including SDH, was associated with a sustained reduction in readmission rates to 2 general pediatric services. Transitional care that addresses multiple domains of family need during a child’s health crisis can help reduce pediatric readmissions.
Post-thoracotomy pain syndrome: seldom severe, often neuropathic, treated unspecific, and insufficient
Authors: Arends Sven , Böhmer Andreas B. , Poels Marcel , Schieren Marc , Koryllos Aris , Wappler Frank , Joppich Robin
Published: March 2020

Background:

Post-thoracotomy pain syndrome (PTPS) is reported with a prevalence ranging between 33% and 91% in literature. However, the difference between open (TT) and video-assisted thoracic surgery (VATS) concerning the prevalence and neuropathic character of PTPS has not yet been systematically investigated. Furthermore, knowledge on analgesic treatment and its efficacy is limited.

Methods:

Structured telephone interviews were conducted with 488 patients 6 to 30 months after TT and VATS. In case of pain, patients received a structured questionnaire including the Leeds Assessment of Neuropathic Symptoms and Signs and Brief Pain Inventory.

Results:

Prevalence of PTPS was 28.6%. 13.2% of patients had a pain intensity Numeric Rating Scale >3, and 4.6% of patients had a pain intensity Numeric Rating Scale >5. In case of PTPS, 63% of patients suffered from neuropathic pain. Post-thoracotomy pain syndrome was more frequent after TT than after VATS (38.0% vs 29.3%, P < 0.05) and in patients younger than 65 years (42.3% vs 26.4%; P < 0.05). TT resulted more often in neuropathic pain (67.7% vs 43.9%; P < 0.05). Forty six percent of PTPS patients received analgesics: 30.3% nonopioids, 25.2% opioids, 10.9% anticonvulsants, and 1.7% antidepressants. Antineuropathic agents were used in 17.4% of patients with neuropathic pain. In 36.7% of patients, the reported reduction of pain was less than 30.0%.

Conclusions:

Post-thoracotomy pain syndrome is not as common as estimated. In most cases, pain intensity is moderate, but patients suffering from severe pain require special attention. They are often heavily disabled due to pain. Tissue-protecting surgery like VATS is beneficial for the prevention of PTPS. Analgesic medications are often underdosed, unspecific for neuropathic pain, and insufficient.
Long-term Voiding and Sexual Function in Male Patients After Robotic Total Mesorectal Excision With Autonomic Nerve Preservation for Rectal Cancer: A Cross-Sectional Study
Authors: Kim Ho Seung , Kang Jae Hyun , Yang Seung Yoon , Kim Nam Kyu
Published: March 2020

Background:

Robotic surgery can help to identify and preserve the autonomic nerves during total mesorectal excision (TME) compared with open surgery or laparoscopy due to the 3-dimensional image and high dexterity of the robotic system. Therefore, this study aimed to assess voiding and sexual function after robotic TME with autonomic nerve preservation. In particular, we focused on the long-term results in male patients operated by a single experienced surgeon.

Materials and Methods:

We surveyed male patients aged 50 years and below at the time of robotic rectal cancer surgery between November 2011 and July 2018. Patients who died and those who had a recurrence and underwent abdominoperineal resection were excluded. The questionnaire covered the International Prostate Symptom Score (IPSS) and the 5-item version of the International Index of Erectile Function (IIEF-5) for voiding and sexual function, respectively.

Results:

Thirty-nine patients (median age, 44 y) were surveyed. IPSS and IIEF-5 scores were 5.7±5.3 and 14.7±8.4, respectively. Only 6 patients (15.4%) complained of poor quality of life due to their urinary symptoms. In sexual function, 10 patients (25.6%) complained severe reduction compared with their preoperative status. The average of postoperative days defined from surgery to the questionnaire was 37.8 months. A significant change in the IIEF-5 score was observed between 1 and 2 years postoperatively (5.8±6.9 vs. 16.5±8.8; P=0.027).

Conclusions:

As we only included male patients who were operated by a single experienced surgeon, the results of robotic TME with pelvic autonomic nerve preservation showed acceptable data in preserving both voiding and sexual functions. Although related clinical factors for poor functional outcomes was not statistically significant due to the small sample size, we could observe an improvement in sexual function between 1 and 2 years after surgery with long-term functional results.
Variation in the Anatomy of the Normal Human Optic Chiasm: An MRI Study
Authors: Bosler Nicholas S. I. , Ashton David , Neely Andrew J. , Lueck Christian J.
Published: March 2020

Background:

Compression of the optic chiasm typically leads to bitemporal hemianopia. This implies that decussating nasal fibers are selectively affected, but the precise mechanism is unclear. Stress on nasal fibers has been investigated using finite element modeling but requires accurate anatomical data to generate a meaningful output. The precise shape of the chiasm is unclear: A recent photomicrographic study suggested that nasal fibers decussate paracentrally and run parallel to each other in the central arm of an “H.” This study aimed to determine the population variation in chiasmal shape to inform future models.

Methods:

Sequential MRI scans of 68 healthy individuals were selected. 2D images of each chiasm were created and analyzed to determine the angle of elevation of the chiasm, the width of the chiasm, and the offset between the points of intersection of lines drawn down the centers of the optic nerves and contralateral optic tracts.

Results:

The mean width of the chiasm was 12.0 ± 1.5 mm (SD), and the mean offset was 4.7 ± 1.4 mm generating a mean offset:width ratio of 0.38 ± 0.09. No chiasm had an offset of zero. The mean incident angle of optic nerves was 56 ± 7°, and for optic tracts, it was 51 ± 7°.

Conclusions:

The human optic chiasm is “H” shaped, not “X” shaped. The findings are consistent with nasal fibers decussating an average of 2.4 mm lateral to the midline before travelling in parallel across the midline. This information will inform future models of chiasmal compression.
The Clinical Utility of Transcranial Magnetic Stimulation in Determining Hemispheric Dominance for Language: A Magnetoencephalography Comparison Study
Authors: Rezaie Roozbeh , Schiller Katherine K. , Embury Luke , Boop Frederick A. , Wheless James W. , Narayana Shalini
Published: March 2020

Purpose:

Transcranial magnetic stimulation (TMS) has recently emerged as a noninvasive alternative to the intracarotid sodium amytal (Wada) procedure for establishing hemispheric dominance (HD) for language. The accuracy of HD determined by TMS was examined by comparing against the HD derived by magnetoencephalography (MEG), a prominent clinical technique with excellent concordance with the Wada procedure.

Methods:

Sixty-seven patients (54 patients ≤18 years) underwent language mapping with TMS and MEG as part of clinical epilepsy and tumor presurgical assessment. Language was mapped in MEG during an auditory word recognition paradigm, and a laterality index was calculated using the number of dipoles and their spatial extent in the two hemispheres. Transcranial magnetic stimulation language mapping was performed as patients performed a naming task, and TMS-induced speech disruptions were recorded during 5-Hz TMS applied to anterior and posterior language cortices. Transcranial magnetic stimulation laterality index was estimated using the number and type of speech disruption in the language regions of each hemisphere.

Results:

Transcranial magnetic stimulation and MEG estimates of HD were concordant in 42 (63%) patients, resulting in a sensitivity of 74% and a specificity of 72%. The overall accuracy of TMS was 73%, equivalent to an odds ratio of 7.35.

Conclusions:

In this first large-scale comparative study in a clinical population, we demonstrate that TMS is a safe and reliable noninvasive tool in determining HD for language. Improving the accuracy of TMS by optimizing TMS parameters and improving task choice will further facilitate the use of TMS to characterize language function, especially in pediatrics.
Nursing documentation for chemotherapy in a university hospital's bone marrow transplant unit: a best practice implementation project
Authors: dos Santos Kelli Borges , Campos Caroline S. , de São José Perrone Ana Carolina Amaral , de Araújo Silva Vieira Camila M. , Coelho Davi Pereira , Hallack-Neto Abrahão Elias , Lockwood Craig , de Araújo Püschel Vilanice Alves
Published: March 2020

Aim:

The aim of this evidence implementation project was to improve the documentation of chemotherapy administration by nursing staff in a bone marrow transplant unit, to improve patient care and safety, as well as meet the legal and educational responsibilities of the nursing staff.

Methods:

This evidence implementation project used the Joanna Briggs Institute's Practical Application of Clinical Evidence System and Getting Research into Practice audit and feedback framework for the design and development of an evidence-based audit and feedback change project. A baseline audit was conducted to assess current practices against best practice and identify areas requiring improvement. Next, the project team reflected on the results of the audit to develop and implement strategies for documentation improvement. Lastly, a follow-up audit was conducted to assess changes in practice improvement.

Results:

The baseline audit results revealed practice areas requiring improvement; facilitators of and barriers to nursing documentation and practice improvement were identified. A checklist, educational session, Nursing Documentation Guidelines for Chemotherapy Administration, was implemented to improve nursing documentation. The follow-up audit demonstrated improved adherence across all audit criteria.

Conclusion:

The checklist implemented for nursing documentation and education contributed to improved practices. To promote additional improvements, nurses will continue to utilize the tools developed and receive continued education through formal training and staff meetings. Future auditing is planned to ensure sustainability.
A retrospective analysis of the dynamic transmission routes of the COVID-19 in mainland China
Authors: Jiang Xiandeng , Chang Le , Shi Yanlin
Published: March 2020

The fourth outbreak of the Coronaviruses, known as the COVID-19, has occurred in Wuhan city of Hubei province in China in December 2019. We propose a time-varying sparse vector autoregressive (VAR) model to retrospectively analyze and visualize the dynamic transmission routes of this outbreak in mainland China over January 31 - February 19, 2020. Our results demonstrate that the influential inter-location routes from Hubei have become unidentifiable since February 4, 2020, whereas the self-transmission in each provincial-level administrative region (location, hereafter) was accelerating over February 4-15, 2020. From February 16, 2020, all routes became less detectable, and no influential transmissions could be identified on February 18 and 19, 2020. Such evidence supports the effectiveness of government interventions, including the travel restrictions in Hubei. Implications of our results suggest that in addition to the origin of the outbreak, virus preventions are of crucial importance in locations with the largest migrant workers percentages (e.g., Jiangxi, Henan and Anhui) to controlling the spread of COVID-19.
Maturity of brain structures and white matter connectomes, and their relationship with psychiatric symptoms in youth
Authors: Luna Alex , Bernanke Joel , Cha Jiook , Posner Jonathan
Published: March 2020

Background

Brain neuromaturation can be indexed using brain predicted age difference (BrainPAD), a metric derived by the application of machine learning (ML) algorithms to neuroimaging. Previous studies in youth have been limited to a single type of imaging data, single ML approach, or specific psychiatric condition. Here, we use multimodal neuroimaging and an ensemble ML algorithm to estimate BrainPAD and examine its relationship with broad measures of symptoms and functioning in youth.

Methods

We used neuroimaging from eligible participants in the Healthy Brain Network (HBN, N = 498). Participants with a Child Behavior Checklist Total Problem T-Score < 60 were split into training (N=215) and test sets (N=48). Morphometry estimates (from structural MRI), white matter connectomes (from diffusion MRI), or both were fed to an automated ML pipeline to develop BrainPAD models. The most accurate model was applied to a held-out evaluation set (N=249), and the association with several psychometrics was estimated.

Results

Models using morphometry and connectomes together had a mean absolute error of 1.16 years, outperforming unimodal models. After dividing participants into positive, normal, and negative BrainPAD groups, negative BrainPAD values were associated with more symptoms on the Child Behavior Checklist (negative=71.6, normal 59.0, p=0.011) and lower functioning on the Children’s Global Assessment Scale (negative=49.3, normal=58.3, p=0.002). Higher scores were associated with better performance on the Flanker task (positive=62.4, normal=52.5, p=0.006).

Conclusion

These findings suggest that a multimodal approach, in combination with an ensemble method, yields a robust biomarker correlated with clinically relevant measures in youth.
Clinical features and outcomes of 221 patients with COVID-19 in Wuhan, China
Authors: Zhang Guqin , Hu Chang , Luo Linjie , Fang Fang , Chen Yongfeng , Li Jianguo , Peng Zhiyong , Pan Huaqin
Published: March 2020

Rationale

In late December 2019, an outbreak of acute respiratory illness, now officially named as COVID-19, or coronavirus disease 2019, emerged in Wuhan, China, now spreading across the whole country and world. More data were needed to understand the clinical characteristics of the disease.

Objectives

To study the epidemiology, clinical features and outcomes of patients with COVID-19.

Methods

we performed a single center, retrospective case series study in 221 patients with laboratory confirmed SARS-CoV-2 pneumonia at a university hospital.

Measurements and Main Results

The median age was 55.0 years and 48.9% were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe pneumonia patients, the median age of the severe patients was significantly older, and they were more likely to have chronic comorbidities. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 33.0% patients showed leukopenia and 73.8% showed lymphopenia. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications. As of February 15, 2020, 19.0% patients had been discharged and 5.4% patients died. 80% of severe cases received ICU care, and 52.3% of them transferred to the general wards due to relieved symptoms, and the mortality rate of severe patients in ICU was 20.5%.

Conclusions

The COVID-19 epidemic spreads rapidly by human-to-human transmission. Patients with elder age, chronic comorbidities, blood leukocyte/lymphocyte count, procalcitonin level, co-infection and severe complications might increase the risk of poor clinical outcomes.
Strong effect ofPenicillium roquefortipopulations on volatile and metabolic compounds responsible for aromas, flavor and texture in blue cheeses
Authors: Caron Thibault , Piver Mélanie Le , Péron Anne-Claire , Lieben Pascale , Lavigne René , Brunel Sammy , Roueyre Daniel , Place Michel , Bonnarme Pascal , Giraud Tatiana , Branca Antoine , Landaud Sophie , Chassard Christophe
Published: March 2020

Studies of food microorganism domestication can provide important insight into adaptation mechanisms and lead to commercial applications.Penicillium roquefortiis a fungus with four genetically differentiated populations, two of which were independently domesticated for blue cheese-making, with the other two populations thriving in other environments. Most blue cheeses are made with strains from a singleP. roquefortipopulation, whereas Roquefort cheeses are inoculated with strains from a second population. We made blue cheeses in accordance with the production specifications for Roquefort-type cheeses, inoculating each cheese with a singleP. roquefortistrain, using a total of three strains from each of the four populations. We investigated differences between the cheeses made with the strains from the fourP. roquefortipopulations, in terms of the induced flora, the proportion of blue color, water activity and the identity and abundance of aqueous and organic metabolites as proxies for proteolysis and lipolysis as well as volatile compounds responsible for flavor and aroma. We found that the population-of-origin of theP. roquefortistrains used for inoculation had a minor impact on bacterial diversity and no effect on the abundance of the main microorganism. The cheeses produced withP. roquefortistrains from cheese populations had a higher percentage of blue area and a higher abundance of the volatile compounds typical of blue cheeses, such as methyl ketones and secondary alcohols. In particular, the Roquefort strains produced higher amounts of these aromatic compounds, partly due to more efficient proteolysis and lipolysis. The Roquefort strains also led to cheeses with a lower water availability, an important feature for preventing spoilage in blue cheeses, which is subject to controls for the sale of Roquefort cheese. The typical appearance and flavors of blue cheeses thus result from human selection onP. roqueforti,leading to the acquisition of specific features by the two cheese populations. These findings have important implications for our understanding of adaptation and domestication, and for cheese improvement.
EvaluatingaroAgene essentiality and EPSP synthase vulnerability inMycobacterium smegmatisunder different nutritional conditions
Authors: Duque-Villegas Mario Alejandro , Abbadi Bruno Lopes , Romero Paulo Ricardo , Galina Luiza , Dalberto Pedro Ferrari , Rodrigues-Junior Valnês da Silva , Roth Candida Deves , Rambo Raoní Scheibler , Vieira de Souza Eduardo , Perello Marcia Alberton , Machado Pablo , Basso Luiz Augusto , Bizarro Cristiano Valim
Published: March 2020

The epidemiological importance of bacteria from the genusMycobacteriumis indisputable and the necessity to find new molecules that can inhibit their growth is urgent. The shikimate pathway, required for the synthesis of important metabolites in bacteria, represents a target for inhibitors ofMycobacterium tuberculosisgrowth. ThearoA-encoded 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) enzyme catalyzes the sixth step of the shikimate pathway. In this study, we combined gene knockout, gene knockdown and kinetic assays to evaluatearoAgene essentiality and the vulnerability of its protein product, EPSPS synthase fromMycobacterium smegmatis(MsEPSPS), under different nutritional conditions. We demonstrate by an allelic exchange-based gene knockout approach the essentiality ofMsEPSPS under rich and poor nutritional conditions. By performing gene complementation experiments with wild-type (WT) and point mutant versions ofaroAgene, together with kinetic assays using WT and mutant recombinant proteins, we show thataroAgene essentiality depends onMsEPSPS activity. To evaluateMsEPSPS vulnerability, we performed gene knockdown experiments using the Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) system. The experiments were performed in both rich and defined (poor) media, using three different repression forces foraroAgene. We only observed growth impairment when bacteria were grown in defined medium without supplementation of aromatic amino acids, thereby indicating thatMsEPSPS vulnerability depends on the environment conditions.

Importance

We evaluated both gene essentiality and target vulnerability of the enzyme that catalyzes the sixth step of the shikimate pathway, thearoA-encoded 5-enolpyruvylshikimate-3-phosphate synthase fromMycobacterium smegmatis(MsEPSPS). Combining gene knockout experiments and kinetic assays, we established a causal link betweenaroAgene essentiality and the biological function of EPSPS protein, which we advocate is an indispensable step for target validation. Moreover, we characterizedMsEPSPS vulnerability under different nutritional conditions and found it is a vulnerable target only whenM. smegmatisis grown under poor nutritional conditions without supplementation with aromatic amino acids. Based on our findings, we suggest that gene essentiality information should be obtained from gene knockout experiments and not knockdown approaches, as even low levels of a protein after gene silencing can lead to a different growth phenotype when compared to that under its complete absence, as was the case witharoAandMsEPSPS in our study.
SOCRATES: An online tool leveraging a social contact data sharing initiative to assess mitigation strategies for COVID-19
Authors: Willem Lander , Van Hoang Thang , Funk Sebastian , Coletti Pietro , Beutels Philippe , Hens Niel
Published: March 2020

Objective

Establishing a social contact data sharing initiative and an interactive tool to assess mitigation strategies for COVID-19.

Results

We organized data sharing of published social contact surveys via online repositories and formatting guidelines. We analyzed this social contact data in terms of weighted social contact matrices, next generation matrices, relative incidence and R0. We incorporated location-specific isolation measures (e.g. school closure or telework) and capture their effect on transmission dynamics. All methods have been implemented in an online application based on R Shiny and applied to COVID-19 with age-specific susceptibility and infectiousness. Using our online tool with the available social contact data, we illustrate that social distancing could have a considerable impact on reducing transmission for COVID-19. The effect itself depends on assumptions made about disease-specific characteristics and the choice of intervention(s).
Clinical findings in critically ill patients infected with SARS-CoV-2 in Guangdong Province, China: a multi-center, retrospective, observational study
Authors: Xu Yonghao , Xu Zhiheng , Liu Xuesong , Cai Lihua , Zheng Haichong , Huang Yongbo , Zhou Lixin , Huang Linxi , Lin Yun , Deng Liehua , Li Jianwei , Chen Sibei , Liu Dongdong , Lin Zhimin , Zhou Liang , He Weiquan , Liu Xiaoqing , Li Yimin
Published: March 2020

Background

In December 2019, human infection with a novel coronavirus, known as SARS-CoV-2, was identified in Wuhan, China. The mortality of critical illness was high in Wuhan. Information about critically ill patients with SARS-CoV-2 infection outside of Wuhan is scarce. We aimed to provide the clinical features, treatment, and prognosis of the critically ill patients with SARS-CoV-2 infection in Guangdong Province.

Methods

In this multi-centered, retrospective, observational study, we enrolled critically ill patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) in Guangdong Province. Demographic data, symptoms, laboratory findings, comorbidities, treatments, and prognosis were collected. Data were compared between patients with and without intubation.

Results

Forty-five critically ill patients with SARS-CoV-2 pneumonia were identified in 7 ICUs in Guangdong Province. The mean age was 56.7 years, and 29 patients (64.4%) were men. The most common symptoms at the onset of illness were high fever and cough. Majority of patients presented with lymphopenia and elevated lactate dehydrogenase. Treatment with antiviral drugs was initiated in all the patients. Thirty-seven patients (82.2%) had developed acute respiratory distress syndrome, and 13 (28.9%) septic shock. A total of 20 (44.4%) patients required intubation and 9 (20%) required extracorporeal membrane oxygenation. As of February 28th 2020, only one patient (2.2%) had died and half of them had discharged of ICU.

Conclusions

Infection with SARS-CoV-2 in critical illness is characterized by fever, lymphopenia, acute respiratory failure and multiple organ dysfunction. Compared with critically ill patients infected with SARS-CoV-2 in Wuhan, the mortality of critically ill patients in Guangdong Province was relatively low. These data provide some general understandings and experience for the critical patients with SARS-CoV-2 outside of Wuhan.
Association of public care in childhood with social, criminal, cognitive, and health outcomes in middle-age: six decades of follow-up of members of the 1958 Birth Cohort Study
Authors: Xie Tiffany H. , de Mestral Carlos , Batty G. David
Published: March 2020

Objectives

To examine if there is an association between childhood public care and adverse life outcomes in middle-age.

Methods

We used data from the United Kingdom 1958 birth cohort study of 18,558 babies. Parents of study members were surveyed at age 7, 11, and 16 years when experience of public care of their offspring was ascertained. An array of outcomes were self-reported by cohort members at age 42 years, and a cognitive test battery was administered at age 50.

Results

420 (3.8%) of 11,160 individuals in the analytical sample experienced childhood public care prior to age 16. Net of confounding factors, public care was linked to half of the twenty-eight non-mutually exclusive endpoints captured in middle-age with the most consistent effects apparent for psychosocial characteristics: 6/7 sociodemographic, 2/2 anti-social, 3/3 psychological, 1/3 health behaviours, 2/8 somatic health, and 0/5 cognitive.

Conclusions

The present study suggests that known associations between childhood care and outcomes in adolescence and early adulthood are also seen in middle-age.

Policy implications

Practitioners in health and social services should perhaps more closely monitor care graduates.
Boysenberry and apple juice concentrate reduces acute lung inflammation through increased alternatively activated macrophage activity in an acute mouse model of allergic airways disease
Authors: Shaw Odette M. , Hurst Roger D , Cooney Janine , Sawyer Gregory M. , Dinnan Hannah , Martell Sheridan
Published: March 2020

Bioactive compounds such as anthocyanins, proanthocyanins and other polyphenols are found in a wide variety of fruits and vegetables, and consumption of these have been associated with reduced lung inflammation and improved lung function in asthma and other lung diseases. We investigated whether a combination of Boysenberry and apple juice, found in BerriQi®Boysenberry and apple juice concentrate, could reduce the allergic airways inflammation associated with asthma. We characterised the polyphenolic components in BerriQi®Boysenberry and apple juice concentrate and identified the main compounds as cyanidin glycosides, ellagitannins, and chlorogenic acid. We found that consumption of 2.5 mg/kg of total anthocyanins from the BerriQi®Boysenberry and apple juice concentrate significantly reduced eosinophil infiltration following acute ovalbumin (OVA) exposure in a mouse model of allergic airways inflammation. We found that BerriQi®Boysenberry and apple juice concentrate consumption increased M2 (CD206+) macrophages and the production of the M2-associated cytokines CXCL10 and CCL4 within the lung. These results suggest that consumption of BerriQi®Boysenberry and apple juice concentrate promotes a shift towards an anti-inflammatory environment within the lung leading to reduced immune cell infiltration and tissue damage.
New microsatellite marker tools for genotype identification and analyses of genetic relationships in two ornamentals, the popular common lilac (Syringa vulgaris) and the invasive garden escapee Himalayan balsam (Impatiens glandulifera)
Authors: Korpelainen Helena , Pietiläinen Maria
Published: March 2020

Nowadays, high-throughput sequencing technologies are widely available. Yet, it is practical to have an access to simpler and cheaper, yet effective low-throughput analyses as well. For that purpose, species-specific microsatellites, also called simple sequence repeats (SSR), are valuable, multi-purpose types of markers. In the present study, we introduce new sets of SSR markers for two ornamental plant species, the popular common lilac (Syringa vulgarisL.) (16 markers) and the invasive garden escapee Himalayan balsam (Impatiens glanduliferaRoyle) (259 markers). The markers were developed as a by-product of a genotyping-by-sequencing project producing a large amount of DNA sequence data. Both the frequency of SSRs and the success rate for marker development were considerably greater inI. glanduliferawhen compared toS. vulgaris. The new markers will contribute to the characterization of germplasm and to other types of genetic analyses on these two species.
Rerouting of ribosomal proteins into splicing in plant organelles
Authors: Wang Chuande , Fourdin Rachel , Quadrado Martine , Dargel-Graffin Céline , Tolleter Dimitri , Macherel David , Mireau Hakim
Published: March 2020

Production and expression of RNAs requires the action of multiple RNA-binding proteins (RBPs). New RBPs are most often created by novel combinations of dedicated RNA binding modules. However, recruiting existing genes to create new RBPs is also an important evolutionary strategy. In this report, we analysed the 8-member uL18 ribosomal protein family in Arabidopsis. uL18 proteins share a short structurally conserved domain that binds the 5S rRNA and allow its incorporation into ribosomes. Our results indicate that Arabidopsis uL18-like proteins are targeted to either mitochondria or chloroplasts. While two members of the family are found in organelle ribosomes, we reveal that two uL18-type proteins correspond to splicing factors that are necessary for the elimination of certain mitochondrial and plastid group II introns. These two proteins do not co-sediment with mitochondrial or plastid ribosomes but associate with the introns whose splicing they promote. Our study thus reveals that the RNA binding capacity of uL18 ribosomal proteins has been detoured to create factors facilitating the elimination of organellar introns.
Extended amygdala-parabrachial circuits alter threat assessment to regulate feeding
Authors: Bhatti Dionnet L. , Luskin Andrew T. , Pedersen Christian E. , Mulvey Bernard , Oden-Brunson Hannah , Kimbell Kate , Sawyer Abbie , Gereau Robert W. , Dougherty Joseph D. , Bruchas Michael R.
Published: March 2020

An animal’s evolutionary success depends on the ability to seek and consume foods while avoiding environmental threats. However, how evolutionarily conserved threat detection circuits modulate feeding is unknown. In mammals, feeding and threat assessment are strongly influenced by the parabrachial nucleus (PBN), a structure that responds to threats and inhibits feeding. Here, we report that the PBN receives dense inputs from the bed nucleus of the stria terminalis (BNST), an extended amygdala structure that encodes affective information. Using a series of complementary approaches, we identify opposing BNST-PBN circuits that modulate a genetically-defined population of PBN neurons to control feeding. This previously unrecognized neural circuit integrates threat assessment with the intrinsic drive to eat.