bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics and Outcomes of Critically Ill Children With Multisystem Inflammatory Syndrome
Authors: Snooks Kellie , Scanlon Matthew C. , Remy Kenneth E. , Shein Steven L. , Klein Margaret J. , Zee-Cheng Janine , Rogerson Colin M. , Rotta Alexandre T. , Lin Anna , McCluskey Casey K. , Carroll Christopher L. 
Published: August 2022

Objectives:
To characterize the prevalence of pediatric critical illness from multisystem inflammatory syndrome in children (MIS-C) and to assess the influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain on outcomes.

Design:
Retrospective cohort study.

Setting:
Database evaluation using the Virtual Pediatric Systems Database.

Patients:
All children with MIS-C admitted to the PICU in 115 contributing hospitals between January 1, 2020, and June 30, 2021.

Measurements and Main Results:
Of the 145,580 children admitted to the PICU during the study period, 1,338 children (0.9%) were admitted with MIS-C with the largest numbers of children admitted in quarter 1 (Q1) of 2021 (n = 626). The original SARS-CoV-2 viral strain and the D614G Strain were the predominant strains through 2020, with Alpha B.1.1.7 predominating in Q1 and quarter 2 (Q2) of 2021. Overall, the median PICU length of stay (LOS) was 2.7 days (25–75% interquartile range [IQR], 1.6–4.7 d) with a median hospital LOS of 6.6 days (25–75% IQR, 4.7–9.3 d); 15.2% received mechanical ventilation with a median duration of mechanical ventilation of 3.1 days (25–75% IQR, 1.9–5.8 d), and there were 11 hospital deaths. During the study period, there was a significant decrease in the median PICU and hospital LOS and a decrease in the frequency of mechanical ventilation, with the most significant decrease occurring between quarter 3 and quarter 4 (Q4) of 2020. Children admitted to a PICU from the general care floor or from another ICU/step-down unit had longer PICU LOS than those admitted directly from an emergency department.

Conclusions:
Overall mortality from MIS-C was low, but the disease burden was high. There was a peak in MIS-C cases during Q1 of 2021, following a shift in viral strains in Q1 of 2021. However, an improvement in MIS-C outcomes starting in Q4 of 2020 suggests that viral strain was not the driving factor for outcomes in this population.
Proton Pump Inhibitor Use and Associated Infectious Complications in the PICU: Propensity Score Matching Analysis
Authors: Goyer Isabelle , Lacotte Edouard , Montreuil Julien , Thibon Pascal , Briant Anaïs R. , Dupont Claire , Parienti Jean-Jacques , Brossier David 
Published: August 2022

OBJECTIVES:
We aimed to evaluate the association between proton pump inhibitor (PPI) exposure and nosocomial infection (NI) during PICU stay.

DESIGN:
Propensity score matched analysis of a single-center retrospective cohort from January 1, 2017, to December 31, 2018.

SETTING:
Tertiary medical and surgical PICU in France.

PATIENTS:
Patients younger than 18 years old, admitted to the PICU with a stay greater than 48 hours.

INTERVENTION:
Patients were retrospectively allocated into two groups and compared depending on whether they received a PPI or not.

MEASUREMENTS AND MAIN RESULTS:
Seven-hundred fifty-four patients were included of which 231 received a PPI (31%). PPIs were mostly used for stress ulcer prophylaxis (174/231; 75%), but upper gastrointestinal bleed risk factors were rarely present (18%). In the unadjusted analyses, the rate of NI was 8% in the PPI exposed group versus 2% in the nonexposed group. After propensity score matching (n = 184 per group), we failed to identify an association between PPI exposure and greater odds of NI (adjusted odds ratio 2.9 [95% CI, 0.9–9.3]; p = 0.082). However, these data have not excluded the possibility that there is up to nine-fold greater odds of NI.

CONCLUSIONS:
This study highlights the prevalent use of PPIs in the PICU, and the potential association between PPIs and nine-fold greater odds of NI is not excluded.
Business of Medicine in the Academic Plastic Surgery Community
Authors: Khetpal Sumun , Hauc Sacha , Lopez Joseph , Prsic Adnan 
Published: August 2022

Purpose
Business fundamentals, such as leadership, negotiations, and personal finance, remain as an overlooked component of residency education. It remains unclear how faculty members in academic plastic surgery particularly view the integration of a business curriculum within plastic surgery residency curriculum and how one's personal exposure to business concepts may impact their perception on the importance of learning such concepts in surgical training.

Methods
A 15-question survey was distributed through the American College of Academic Plastic Surgeons members in order to assess how academic plastic surgeons perceived the importance of a business curriculum and, if applicable, how the formalized study of these concepts were incorporated within plastic surgery residency programs. Surgeons were also queried about barriers toward organizing and executing such a curriculum and about the importance of certain topics for education.

Results
Fifty-five academic plastic surgeons, representing 25 institutions, completed the survey. More than 60% of academic plastic surgeons either strongly agreed or agreed to a formalized business curriculum being a necessary component of residency curriculum, and more than 70% either strongly agreed or agreed to wishing for more instruction in such concepts.

Conclusion
This study elucidates how academic plastic surgeons perceive the education of business fundamentals during plastic surgery training. Although the majority of respondents found such teachings as valuable, our findings suggest limited resources allocated to these important concepts. Future efforts should incentivize plastic surgery programs to provide formal instruction within the business of medicine and, in doing so, position trainees for success in their careers.
Evaluation of RT-PCR pooling test for the detection of SARS-CoV-2 in low-resource setting
Authors: Maharjan Narayani , Thapa Niresh , Magar Bibek Pun , Maharjan Muna , Tu Jiancheng 
Published: August 2022

AbstractBackgroundSpecimen pooling is an efficient method when there is limited accessibility or scarcity of test kits and reagents for nucleic acid extraction and molecular detection. We evaluated the ability of the standard real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test for detecting a single positive sample of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within a pool of negative samples and to find out the maximum pool dilution limit up to which a single positive sample can be detected.MethodsRNA extracts from nasopharyngeal and oropharyngeal samples were pooled for the detection of the SARS-CoV-2 virus by RT-PCR. Positive samples were serially diluted in negative samples pools with dilutions ranging from 1/2 to 1/64 to estimate the optimal pool size. The viral transport medium (VTM) of three positive samples was also evaluated for optimal pool size determination.ResultsA single positive sample with a Cycle threshold (Ct) value range from 16-23 (high viral load) can be detected in dilution pools upto1/64 for both genes. In pooling before RNA extraction, a positive sample with a low Ct value (13) and intermediate Ct value (25) was detected till 1/32 dilution pool but a positive sample with a high Ct value (32) was not detected further 1/4 dilution. Besides, two positive VTM samples were detected in pools of sizes 5, 8, and 10.ConclusionsThis study concluded that sample testing by pooling is reliable if done properly and can help increase testing capacity in a low-resource setting.
Seasonal variations in social contact patterns in a rural population in north India: Implications for pandemic control
Authors: Nagpal Sargun , Kumar Rakesh , Noronha Riz Fernando , Kumar Supriya , Gupta Debayan , Amarchand Ritvik , Gosain Mudita , Sharma Hanspria , Menon Gautam I. , Krishnan Anand 
Published: August 2022

AbstractSocial contact mixing patterns are critical to the transmission of communicable diseases and have been employed to model disease outbreaks including COVID-19. Nonetheless, there is a paucity of studies on contact mixing in low and middle-income countries such as India. Furthermore, mathematical models of disease outbreaks do not account for the temporal nature of social contacts. We conducted a longitudinal study of social contacts in rural north India across three seasons and analysed the temporal differences in contact patterns.A contact diary survey was performed across three seasons from October 2015-16, in which participants were queried on the number, duration, and characteristics of contacts that occurred on the previous day. A total of 8,421 responses from 3,052 respondents (49% females) recorded characteristics of 180,073 contacts. Respondents reported a significantly higher number and duration of contacts in the winter, followed by the summer and the monsoon season (Nemenyi post-hoc, p<0.001). Participants aged 0-9 years and 10-19 years of age reported the highest median number of contacts (16 (IQR 12-21), 17 (IQR 13-24) respectively) and were found to have the highest node centrality in the social network of the region (pageranks = 0.20, 0.17). Employed males across all age groups were found to have a higher number of contacts than unemployed males (Negative Binomial Regression: rate ratio 1.18, 95% CI: 1.05-1.31). A large proportion (>80%) of contacts that were reported in schools or on public transport involved physical contact.To the best of our knowledge, our study is the first from India to show that contact mixing patterns vary by the time of the year and provides useful implications for pandemic control. Our results can be used to parameterize more accurate mathematical models for prediction of epidemiological trends of infections in rural India.
Symptom presentation among SARS-CoV-2 positive cases and the impact of COVID-19 vaccination; three prospective household cohorts
Authors: Westerhof Ilse , de Hoog Marieke , Ieven Margareta , Lammens Christine , van Beek Janko , Rozhnova Ganna , Eggink Dirk , Euser Sjoerd , Wildenbeest Joanne , Duijts Liesbeth , van Houten Marlies , Goossens Herman , Giaquinto Carlo , Bruijning-Verhagen Patricia 
Published: August 2022

AbstractOBJECTIVEUsing data from European prospective household studies, we systematically compared the symptom burden of the wild-type and Alpha variant infected individuals versus the Omicron BA.1 and BA.2 infected individuals across paediatric and adult age-groups. In addition, we measured the impact of COVID-19 vaccination on the Omicron symptom burden.METHODSThe household transmission studies were conducted during the wild-type and Alpha period (April 2020 to April 2021) and the early Omicron BA.1 and BA.2 dominant period (January to March 2022). All three studies used similar protocols. Households were prospectively followed from detection of the first SARS-CoV-2 index case until at least day 21 including (repeated) PCR testing, paired serology and daily symptom reporting for all household members. To avoid possible index-case ascertainment bias, we restricted analyses to secondary household cases. Age-stratified SARS-CoV-2 symptom burden was compared for wild-type/Alpha versus Omicron infections and for primary versus primary plus booster series vaccinated adult cases.FINDINGSIn total 216 secondary cases from wild-type/Alpha, and 130 from the Omicron period were included. Unvaccinated children <12 years experienced more symptoms and higher maximum and cumulative severity scores during the Omicron compared to the wild-type/Alpha period (p=0.004, p=0.011 and p=0.075, respectively). In adults, disease duration and maximum and cumulative severity scores were reduced during the Omicron period. Adjusted for age, gender and prior immunity Omicron was associated with lower odds for loss of smell or taste (Odds Ratio [OR]: 0.14; 95%CI 0.03-0.50), and higher, but non-significant odds for upper respiratory symptoms, fever and fatigue (ORs varying between 1.85-2.23). Comparing primary versus primary plus booster vaccinated adult cases during the Omicron period no differences were observed in disease severity or duration (p≥0.12).INTERPRETATIONIn children, the Omicron variant causes higher symptom burden compared to the wild-type/Alpha. Adults experienced a lower symptom burden possibly due to prior vaccination. A shift in most frequently reported symptoms occurred with a marked reduction in loss of smell or taste during the Omicron period. An additional effect of booster vaccination on symptom severity in infected adults compared to primary series only, could not be demonstrated.
Differentiation of human induced pluripotent stem cells into cortical neural stem cells
Authors: Neaverson Alexandra , Andersson Malin H. L. , Arshad Osama A. , Foulser Luke , Goodwin-Trotman Mary , Hunter Adam , Newman Ben , Patel Minal , Roth Charlotte , Thwaites Tristan , Kilpinen Helena , Hurles Matthew E. , Day Andrew , Gerety Sebastian S. 
Published: August 2022

AbstractEfficient and effective methods for converting human induced pluripotent stem cells (iPSC) into differentiated derivatives are critical for performing robust, large-scale studies of development and disease modelling, and for providing a source of cells for regenerative medicine. Here, we describe a 14-day neural differentiation protocol which allows for the scalable, simultaneous differentiation of multiple iPSC lines into cortical neural stem cells (NSCs). We currently employ this protocol to differentiate and compare sets of engineered iPSC lines carrying loss of function alleles in developmental disorder associated genes, alongside isogenic wildtype controls. Using RNA sequencing (RNA-Seq), we can examine the changes in gene expression brought about by each disease gene knockout, to determine its impact on neural development and explore mechanisms of disease. The 10-day Neural Induction period uses the well established dual-SMAD inhibition approach combined with Wnt/β-Catenin inhibition to selectively induce formation of cortical NSCs. This is followed by a 4-day Neural Maintenance period facilitating NSC expansion and rosette formation, and NSC cryopreservation. We also describe methods for thawing and passaging the cryopreserved NSCs, which are useful in confirming their viability for further culture. Routine implementation of ICC Quality Control confirms the presence of PAX6-positive and/or FOXG1-positive NSCs and the absence of OCT4-positive iPSCs after differentiation. RNA-Seq, flow cytometry, immunocytochemistry (ICC) and RT-qPCR provide additional confirmation of robust presence of NSC markers in the differentiated cells. The broader utility and application of our protocol is demonstrated by the successful differentiation of wildtype iPSC lines from five additional independent donors. This paper thereby describes an efficient method for the production of large numbers of high purity cortical NSCs, which are widely applicable for downstream research into developmental mechanisms, further differentiation into postmitotic cortical neurons, or other applications such as large-scale drug screening experiments.
Prosocial behavior, social reward and affective state discrimination in adult male and female mice
Authors: Misiołek Klaudia , Klimczak Marta , Chrószcz Magdalena , Szumiec Łukasz , Bryksa Anna , Przyborowicz Karolina , Rodriguez Parkitna Jan , Harda Zofia 
Published: August 2022

AbstractProsocial behavior, defined as voluntary behavior intended to benefit another, has long been regarded as a primarily human characteristic. In recent years, it was reported that laboratory animals also favor prosocial choices in various experimental paradigms, thus demonstrating that prosocial behaviors are evolutionarily conserved. Here, we investigated prosocial choices in adult male and female C57BL/6 laboratory mice in a task where a subject mouse is equally rewarded for entering any of the two compartments of the experimental cage, but only entering of the compartment designated as “prosocial” rewards an interaction partner. In parallel we have also assessed two traits that are regarded as closely related to prosociality: sensitivity to social reward and the ability to recognize the affective state of another individual. We find that female, but not male, mice increased frequency of prosocial choices from pretest to test. At the same time, both sexes showed similar rewarding effects of social contact in the conditioned place preference test, and similarly, there was no effect of sex on affective state discrimination measured as the preference for interaction with a hungry or relieved mouse over a neutral animal. These observations bring interesting parallels to differences between sexes observed in humans, and are in line with reported higher propensity for prosocial behavior in human females, but differ with regard to sensitivity to social stimuli in males.
Magnetogenetic closed-loop reduction of seizure activity in a rat model of epilepsy
Authors: Metto Abigael C. , Gilad Assaf A. , Pelled Galit 
Published: August 2022

AbstractOn-demand neurostimulation has shown success in epilepsy patients with pharmacoresistant seizures. Seizures produce magnetic fields that can be recorded using magnetoencephalography. We developed a new closed-loop approach to control seizure activity based on magnetogenetics using the electromagnetic perceptive gene (EPG) that encodes a protein that responds to magnetic fields. The EPG transgene was expressed in inhibitory interneurons under hDlx promoter and kainic acid was used to induce acute seizures. In vivo electrophysiological signals were recorded. We found that hDlx EPG rats exhibited a significant delay in the onset of first seizure (1142.72 ± 186.35s) compared to controls (644.03 ± 15.06s) and significantly less seizures (4.11 ± 1.03) compared to controls (8.33 ± 1.58). These preliminary findings suggest that on-demand activation of EPG expressed in inhibitory interneurons suppress seizure activity, and magnetogenetics via EPG may be an effective strategy to alleviate seizure severity in a minimally invasive, closed-loop and cell-specific fashion.
Noisy neuronal populations effectively encode sound localization in the dorsal inferior colliculus of awake mice
Authors: Boffi Juan C. , Bathellier Brice , Asari Hiroki , Prevedel Robert 
Published: August 2022

AbstractSound location coding has been extensively studied at the central nucleus of the mammalian inferior colliculus (CNIC), supporting a population code. However, this population code has not been extensively characterized on the single-trial level with simultaneous recordings or at other anatomical regions like the dorsal cortex of inferior colliculus (DCIC), which is relevant for learning-induced experience dependent plasticity. To address these knowledge gaps, here we made in two complementary ways large-scale recordings of DCIC populations from awake mice in response to sounds delivered from 13 different frontal horizontal locations (azimuths): volumetric two-photon calcium imaging with ∼700 cells simultaneously recorded at a relatively low temporal resolution, and high-density single-unit extracellular recordings with ∼20 cells simultaneously recorded at a high temporal resolution. Independent of the method, the recorded DCIC population responses revealed substantial trial-to-trial variation (neuronal noise) which was significantly correlated across pairs of neurons (noise correlations) in the passively listening condition. Nevertheless, decoding analysis supported that these noisy response patterns encode sound location on the single-trial basis, reaching errors that match the discrimination ability of mice. The detected noise correlations contributed to minimize the error of the DCIC population code of sound azimuth. Altogether these findings point out that DCIC can encode sound location in a similar format to what has been proposed for CNIC, opening exciting questions about how noise correlations could shape this code in the context of cortico-collicular input and experience dependent plasticity.
α-Synuclein pathology and reduced neurogenesis in the olfactory system affect olfaction in a mouse model of Parkinson’s disease
Authors: Martin-Lopez Eduardo , Vidyadhara D.J. , Liberia Teresa , Meller Sarah J. , Harmon Leah E. , Hsu Ryan M. , Han Kimberly , Yücel Betül , Chandra Sreeganga S. , Greer Charles A. 
Published: August 2022

AbstractParkinson’s Disease (PD) is characterized by multiple symptoms including olfactory dysfunction, whose underlying mechanisms remain unclear. Here, we explored pathological changes in the olfactory pathway of transgenic (Tg) mice expressing the human A30P mutant α-synuclein (α-syn) (α-syn-Tg mice) at 6-7 and 12-14 months of age, representing early and late-stages of motor progression, respectively. α-Syn-Tg mice at late stages exhibited olfactory behavioral deficits, which correlated with severe α-syn pathology in projection neurons of the olfactory pathway. In parallel, olfactory bulb (OB) neurogenesis in α-syn-Tg mice was reduced in the OB granule cells at 6-7 months, and OB periglomerular cells at 12-14 months, respectively, both of which could contribute to olfactory dysfunction. Proteomic analyses showed a disruption in endo- and exocytic pathways in the OB during the early stages which appeared exacerbated at the synaptic terminals when the mice developed olfactory deficits at 12-14 months. Our data suggest that, 1) the α-syn-Tg mice recapitulate the olfactory functional deficits seen in PD; 2) olfactory structures exhibit spatiotemporal disparities for vulnerability to α-syn pathology; 3) α-syn pathology is restricted to projection neurons in the olfactory pathway; 4) neurogenesis in adult α-syn-Tg mice is reduced in the OB; and 5) synaptic endo- and exocytosis defects in the OB may further explain olfactory deficits.
Geometric differences in the ribosome exit tunnel impact the escape of small nascent proteins
Authors: Yu Shiqi , Srebnik Simcha , Duc Khanh Dao 
Published: August 2022

AbstractThe exit tunnel is the sub-compartment of the ribosome that contains the nascent polypeptide chain and as such, is involved in various vital functions, including regulation of translation and protein folding. As the geometry of the tunnel shows important differences across species, we focus on key geometrical features of eukaryote and prokaryote tunnels. We used a simple coarse-grained molecular dynamics model to study the role of the tunnel geometry in the post-translational escape of short proteins (sORF’s), with lengths ranging from 6 to 56 amino acids. We found that the probability of escape for prokaryotes is one for all but the 12-mer chains. Moreover, proteins of this length have an extremely low escape probability in eukaryotes. A detailed examination of the associated single trajectories and energy profiles showed that these variations can be explained by the interplay between the protein configurational space and the confinement effects introduced by the constriction sites of the ribosome exit tunnel. For certain lengths, either one or both of the constriction sites can lead to the trapping of the protein in the “pocket” regions preceding these sites. As the distribution of existing sORF’s indicate some bias in length that is consistent with our findings, we finally suggest that the constraints imposed by the tunnel geometry have impacted the evolution of sORF’s.