bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nasal Alar Surface Area Differences After Unilateral Cleft Lip Repair: Long-Term Effects of the Perialar Incision
Authors: Perdanasari Aurelia Trisliana , Wagner Ryan D. , Davis Matthew J. , Masoumy Mohamad , Eisemann Bradley S. , Olshinka Asaf , Buchanan Edward P. 
Published: March 2020

Background:
The Millard rotation-advancement cleft lip repair is the most commonly performed cleft lip repair. An extended perialar incision allows for further advancement of the lateral lip element and improved positioning of the alar base. There is a lack of data evaluating differences in nasal alar growth when the perialar incision is utilized. This study compares the long-term effects of a perialar incision on the alar surface area of unilateral cleft lip patients who underwent a Millard cleft lip repair.

Methods:
Thirty-seven patients with a diagnosis of unilateral cleft lip treated with a Millard primary lip repair were studied. A perialar incision was utilized in 16 patients while 21 patients underwent a standard Millard repair. 3dMD facial images were taken at least 10 years after the initial lip repair. Using the patient's non-cleft side as an internal control, the Alar Ratio (AR) was calculated, defined as the cleft alar surface area divided by the non-cleft alar surface area.

Results:
The AR was significantly greater in the standard Millard repair group compared to the perialar incision group, 0.74 and 0.64 respectively (P = .02). The incomplete cleft population demonstrated a more profound difference between the treatment groups (0.82 and 0.62, respectively).

Conclusions:
This study reveals an association between a perialar incision and decreased alar surface area. Long-term follow up results suggest a perialar scar restricts alar growth leading to significant asymmetry between the cleft and non-cleft sides. Therefore, surgical technique must be carefully considered prior to utilizing a perialar incision during unilateral cleft lip repair.
Does the Technique for Assessing Loss of Resistance Alter the Magnitude of Epidural Needle Tip Overshoot?
Authors: Cometa M. Anthony , Lopez Brandon M. , Vasilopoulos Terrie , Destephens Anthony J. , Bigos André , Lizdas David E. , Gravenstein Nikolaus , Lampotang Samsun 
Published: March 2020

Introduction
Postdural puncture headache due to accidental dural puncture is a consequence of excessive needle tip overshoot distance after entering the epidural space via a loss of resistance (LOR) technique. We are not aware of any quantitative comparison of the magnitude of needle tip overshoot (distance traveled by the needle tip beyond the point where LOR can be discerned) for the various LOR assessment techniques that are taught. Such a comparison may provide insight into contributing factors of accidental dural puncture and associated postdural puncture headache.

Methods
A custom-built simulator was used to evaluate the following 3 LOR assessment techniques: incremental needle advancement, intermittent LOR assessment (II); continuous needle advancement, high-frequency intermittent LOR assessment (CI); and continuous needle advancement, continuous LOR assessment (CC).

Results
There were significant mean differences in maximum overshoot past a virtual LOR plane due to technique (F
(2,124) = 79.31, P < 0.001) (Fig. 2). Specifically, maximum overshoot was greater with technique II [mean = 3.8 mm, 95% confidence interval (CI) = 3.4–4.3] versus either CC (mean = 1.9 mm, 95% CI = 1.5–1.8, P < 0.001) or CI (mean = 1.4 mm, 95% CI = 0.9–2.3, P < 0.001). Differences in maximum overshoot between CC and CI were not statistically different (P = 0.996). Maximum overshoot was greater at 4 cm (mean = 3.0 mm, 95% CI = 2.6–3.4) compared with 5 cm (mean = 2.3 mm, 95% CI = 2.0–2.5, P = 0.044), 6 cm (mean = 2.0 mm, 95% CI = 1.9–2.2, P = 0.054), 7 cm (mean = 1.9 mm, 95% CI = 1.7–2.1, P = 0.002), and 8 cm (mean = 1.8 mm, 95% CI = 1.6–2.1, P = 0.001). In addition, maximum overshoot at 5 cm was greater than that at 7 cm (P = 0.020) and 8 cm (P = 0.037). The other LOR depths were not statistically significantly different from each other. Depth did not have a significant interaction with technique (P = 0.517). Technique preference had neither a significant relationship to maximum overshoot (P = 0.588) nor a significant interaction with LOR assessment technique (P = 0.689).

Discussion
Technique II LOR assessment produced the greatest needle overshoot past the simulated LOR plane after obtaining LOR. This was consistent across all LOR depths. In this bench study, the II technique resulted in the deepest needle tip maximum overshoot. We are in the process of designing a clinical study to collect similar data in patients.
Impact of Simulation-Based Learning on National Ranking Medical Examination Results in France
Authors: Galland Joris , Martis Nihal , Levraut Michael , Hani Hind , Baumann Cedric , Fournier Jean-Paul , Braun Marc 
Published: March 2020

Introduction
In France, the National Ranking Examination (ECNi) evaluates medical students based on their clinical reasoning. Simulation-based education on ECNi preparation has not been assessed. Our objective is to establish the added value of high-fidelity (HF) simulation-based learning in ECNi preparation compared with the current standard.

Methods
We performed a controlled, prospective study. Fifth-year medical students from Nancy and Nice participated in a 3-phase process. In phase 1, students were tested on 6 themes (A–F) that were each presented as an ECNi clinical case and were randomized into 2 groups (#1 and #2). A 20-point grading scale was used. In phase 2, group #1 carried out HF simulation on themes A, B, and C, whereas group #2 did so on themes D, E, and F. Students were tested, in phase 3, with a new set of clinical cases on the same 6 themes. Progression in scores between phases 1 and 3 was analyzed.

Results
One hundred sixty-six medical students randomized into 2 groups partook in the study. In phase 1, there was no significant difference in scores between groups. In phase 3, group #1 had significantly higher scores than group #2 for cases A, B, and C. Scores were significantly higher in group #2 for cases D, E, and F. Average scoring significantly improved between phases 1 and 3 with a 1.4-point gain for cases A, B, and C in group #1 and a 2.10-point gain for cases D, E, and F in group #2.

Conclusions
Our study shows that HF simulation learning significantly increases ECNi-like test results when compared with traditional forms.
Association of SAPAP3 allelic variants with symptom dimensions and pharmacological treatment response in obsessive-compulsive disorder
Authors: Naaz Safoora , Balachander Srinivas , Murthy Nithyananda Srinivasa , Bhagyalakshmi MS , Sud Reeteka , Saha Priyanka , Narayanaswamy Janardhanan C , Janardhan Reddy YC , Jain Sanjeev , Purushottam Meera , Viswanath Biju 
Published: March 2020

AbstractBackgroundThough several SAPAP3 gene knockout studies in mice have implicated its role in compulsivity, human studies have failed to demonstrate its association with obsessive-compulsive disorder (OCD). We examined the association between allelic variants of a single nucleotide polymorphism in the SAPAP3 gene (rs6662980) with specific aspects of the OCD phenotype.MethodsA total of 200 subjects with OCD were genotyped using the TaqMan assay. All subjects were assessed using Mini International Neuropsychiatric Interview, the Yale-Brown Obsessive-Compulsive Scale, and their treatment response was evaluated over naturalistic treatment and follow-up.ResultsAfter correcting for multiple comparisons, G-allele at rs6662980 was found to be associated with contamination/washing symptoms (p=0.003). Logistic regression analysis also showed that presence of G allele predicted poor response to serotonin reuptake inhibitors [odds ratio = 2.473 (95% CI = 1.157 - 5.407), p=0.021]. Interaction between presence of G-allele and contamination factor score predicted SRI resistance (B= 1.197, p = 0.006).LimitationsWe did not use a dimensional measure for assessing OCD symptoms. Treatment response was assessed over naturalistic follow-up.ConclusionSpecific phenotypic manifestations of OCD, which include contamination and washing-related symptoms along with resistance to serotonin reuptake inhibitors, may be related to alterations in the SAPAP3 gene.Public Significance Statement“This study finds that a specific polymorphism in the SAPAP3 gene, was found to be associated with the contamination/washing symptoms of OCD and was also found to predict resistance to pharmacological treatment”HighlightsSAPAP3 gene is implicated in OCDAssociation of SAPAP3 gene (rs6662980) with OCD phenotypes was examinedPresence of the minor (G) allele predicted contamination & washing symptomsSAPAP3 polymorphism had a significant association with treatment responseInteraction between presence of G-allele and contamination factor score predicted treatment resistance
Analysis clinical features of COVID-19 infection in secondary epidemic area and report potential biomarkers in evaluation
Authors: Ji Weiping , Bishnu Gautam , Cai Zhenzhai , Shen Xian 
Published: March 2020

AbstractObjectiveBased on the clinical characteristics of infected patients with novel coronavirus in secondary epidemic areas, we aimed to identify potential biomarkers for the evaluation of novel coronavirus-infected patients, guide the diagnosis and treatment of this disease in secondary epidemic areas and provide a reference for the clinical prevention and control of this epidemic situation.MethodsThe clinical data of 33 patients with respiratory symptoms caused by the novel coronavirus in Wenzhou city from January 15 to February 12, 2020, were thoroughly reviewed. At the onset of the disease, we found that the primary symptoms were fever, cough, fatigue, chest tightness, chest pain and specific blood test results. According to the patients’ histories, the patients were divided into two groups: those who spent time in the main epidemic area and those who did not spend time in the main epidemic area. The differences in the clinical manifestations between these two groups were analyzed.ResultsThe main clinical symptoms of patients infected with novel coronavirus in the secondary epidemic area were respiratory tract ailments and systemic symptoms. After grouping patients based on the presence or absence of residency in or travel history to the main epidemic area, there was no significant difference between the baseline data of these two groups, and there were no significant differences in symptoms and signs between the two groups (P>0.05). Some patients had abnormally increased serum amyloid protein A (SAA). There were statistically significant differences in the leukocyte count/C-reactive protein, monocyte ratio/C-reactive protein, neutrophil count/C-reactive protein, monocyte count/C-reactive protein and hemoglobin/C-reactive protein values between the two groups (P < 0.05).ConclusionRespiratory tract ailments and systemic symptoms were the primary symptoms of novel coronavirus infection in the secondary epidemic area; these symptoms are not typical. The abnormal increase in serum amyloid protein (SAA) may be used as an auxiliary index for diagnosis and treatment. CRP changes before other blood parameters and thus may be an effective evaluation index for patients with COVID-19 infection.
Inferring the number of COVID-19 cases from recently reported deaths
Authors: Jombart Thibaut , van Zandvoort Kevin , Russell Timothy W , Jarvis Christopher I , Gimma Amy , Abbott Sam , Clifford Sam , Funk Sebastian , Gibbs Hamish , Liu Yang , Pearson Carl A. B. , Bosse Nikos I ,   Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Eggo Rosalind M , Kucharski Adam J , Edmunds W John 
Published: March 2020

ABSTRACTWe estimate the number of COVID-19 cases from newly reported deaths in a population without previous reports. Our results suggest that by the time a single death occurs, hundreds to thousands of cases are likely to be present in that population. This suggests containment via contact tracing will be challenging at this point, and other response strategies should be considered. Our approach is implemented in a publicly available, user-friendly, online tool.
Belowground changes to community structure alter methane-cycling dynamics in Amazonia
Authors: Meyer Kyle M. , Morris Andrew H. , Webster Kevin , Klein Ann M. , Kroeger Marie E. , Meredith Laura K. , Brændholt Andreas , Nakamura Fernanda , Venturini Andressa , de Souza Leandro Fonseca , Shek Katherine L. , Danielson Rachel , van Haren Joost , de Camargo Plinio Barbosa , Tsai Siu Mui , Dini-Andreote Fernando , de Mauro José M. S. , Nüsslein Klaus , Saleska Scott , Rodrigues Jorge L. M. , Bohannan Brendan J. M. 
Published: March 2020

ABSTRACTAmazonian rainforest is undergoing increasing rates of deforestation, driven primarily by cattle pasture expansion. Forest-to-pasture conversion has been associated with changes to ecosystem processes, including substantial increases in soil methane (CH4) emission. The drivers of this change in CH4flux are not well understood. To address this knowledge gap, we measured soil CH4flux, environmental conditions, and belowground microbial community attributes across a land use change gradient (old growth primary forest, cattle pasture, and secondary forest regrowth) in two Amazon Basin regions. Primary forest soils exhibited CH4uptake at modest rates, while pasture soils exhibited CH4emission at high but variable rates. Secondary forest soils exhibited low rates of CH4uptake, suggesting that forest regrowth following pasture abandonment could reverse the CH4sink-to-source trend. While few environmental variables were significantly associated with CH4flux, we identified numerous microbial community attributes in the surface soil that explained substantial variation in CH4flux with land use change. Among the strongest predictors were the relative abundance and diversity of methanogens, which both increased in pasture relative to forests. We further identified individual taxa that were associated with CH4fluxes and which collectively explained ~50% of flux variance. These taxa included methanogens and methanotrophs, as well as taxa that may indirectly influence CH4flux through acetate production, iron reduction, and nitrogen transformations. Each land type had a unique subset of taxa associated with CH4fluxes, suggesting that land use change alters CH4cycling through shifts in microbial community composition. Taken together, our results suggest that changes in CH4flux from agricultural conversion could be driven by microbial responses to land use change in the surface soil, with both direct and indirect effects on CH4cycling. This demonstrates the central role of microorganisms in mediating ecosystem responses to land use change in the Amazon Basin.
Third generation sequencing revises the molecular karyotype forToxoplasma gondiiand identifies emerging copy number variants in sexual recombinants
Authors: Xia Jing , Venkat Aarthi , Reese Michael L. , Le Roch Karine , Ay Ferhat , Boyle Jon P. 
Published: March 2020

ABSTRACTToxoplasma gondiiis an obligate intracellular parasite that has a significant impact on human health, especially in the immunocompromised. This parasite is also a useful genetic model for intracellular parasitism given its ease of culture in the laboratory and relevant animal models. However, as for many other eukaryotes, theT. gondiigenome is incomplete, containing hundreds of sequence gaps due to the presence of repetitive and/or uncloneable sequences that prevent complete telomere-to-telomere de novo chromosome assembly. Here, we report the first use of single molecule DNA sequencing to generate near complete de novo genome assemblies forT. gondiiand its near relative,N. caninum. Using the Oxford Nanopore Minion platform, we dramatically improved the contiguity of theT. gondiigenome (N50 of ∼6.6Mb) and increased overall assembled sequence compared to current reference sequences by ∼2 Mb. Multiple complete chromosomes were fully assembled as evidenced by clear telomeric repeats on the end of each contig. Interestingly, for all of theToxoplasma gondiistrains that we sequenced (RH, CTG, II×III F1 progeny clones CL13, S27, S21, and S26), the largest contig ranged in size between 11.9 and 12.1 Mb in size, which is larger than any previously reportedT. gondiichromosome. This was due to a repeatable and consistent fusion of chromosomes VIIb and VIII. These data were further validated by mapping existingT. gondiiME49 Hi-C data to our assembly, providing parallel lines of evidence that theT. gondiikaryotype consists of 13, rather than 14, chromosomes. In addition revising the molecular karyotype we were also able to resolve hundreds of repeats derived from both coding and non-coding tandem sequence expansions. For well-known host-targeting effector loci like rhoptry protein 5 (ROP5) and ROP38, we were also able to accurately determine the precise gene count, order and orientation using established assembly approaches and the most likely primary sequence of each using our own assembly correction scripts tailored to correcting homopolymeric run errors in tandem sequence arrays. Finally, when we compared theT. gondiiandN. caninumassemblies we found that while the 13 chromosome karyotype was conserved, we determined that previously unidentified large scale translocation events occurred inT. gondiiandN. caninumsince their most recent common ancestry.
Molecular identification of sixty-three amacrine cell types completes a mouse retinal cell atlas
Authors: Yan Wenjun , Laboulaye Mallory A. , Tran Nicholas M. , Whitney Irene E. , Benhar Inbal , Sanes Joshua R. 
Published: March 2020

ABSTRACTAmacrine cells (ACs) are a diverse class of interneurons that modulate input from photoreceptors to retinal ganglion cells (RGCs), rendering each RGC type selectively sensitive to particular visual features, which are then relayed to the brain. While many AC types have been identified morphologically and physiologically, they have not been comprehensively classified or molecularly characterized. We used high-throughput single-cell RNA sequencing (scRNA-seq) to profile >32,000 ACs from mouse retina, and applied computational methods to identify 63 AC types. We identified molecular markers for each type, and used them to characterize the morphology of multiple types. We show that they include nearly all previously known AC types as well as many that had not been described. Consistent with previous studies, most of the AC types express markers for the canonical inhibitory neurotransmitters GABA or glycine, but several express neither or both. In addition, many express one or more neuropeptides, and two express glutamatergic markers. We also explored transcriptomic relationships among AC types and identified transcription factors expressed by individual or multiple closely related types. Noteworthy among these wereMeis2andTcf4, expressed by most GABAergic and most glycinergic types, respectively. Together, these results provide a foundation for developmental and functional studies of ACs, as well as means for genetically accessing them. Along with previous molecular, physiological and morphological analyses, they establish the existence of at least 130 neuronal types and nearly 140 cell types in mouse retina.SIGNIFICANCE STATEMENTThe mouse retina is a leading model for analyzing the development, structure, function and pathology of neural circuits. A complete molecular atlas of retinal cell types provides an important foundation for these studies. We used high-throughput single-cell RNA sequencing (scRNA-seq) to characterize the most heterogeneous class of retinal interneurons, amacrine cells, identifying 63 distinct types. The atlas includes types identified previously as well as many novel types. We provide evidence for use of multiple neurotransmitters and neuropeptides and identify transcription factors expressed by groups of closely related types. Combining these results with those obtained previously, we proposed that the mouse retina contains 130 neuronal types, and is therefore comparable in complexity to other regions of the brain.
Ventral tegmental dopamine neurons control the impulse vector during motivated behavior
Authors: Hughes Ryan N. , Bakhurin Konstantin I. , Petter Elijah A. , Watson Glenn D.R. , Kim Namsoo , Friedman Alexander D. , Yin Henry H. 
Published: March 2020

AbstractThe Ventral Tegmental Area (VTA) is a major source of dopamine, especially to the limbic brain regions. Despite decades of research, the function of VTA dopamine neurons remains controversial. Here, using a novel head-fixed behavioral system with five orthogonal force sensors, we show for the first time that distinct populations of VTA dopamine activity precisely represent the impulse vector (force exerted over time) generated by the animal. Optogenetic excitation of VTA dopamine neurons quantitatively determines impulse in the forward direction, and optogenetic inhibition produces impulse in the backward direction. At the same time, these neurons also regulate the initiation and execution of anticipatory licking. Our results indicate that VTA controls the magnitude, direction, and duration of force used to move towards or away from any motivationally relevant stimuli.One Sentence SummaryVTA dopamine bidirectionally controls impulse vector and anticipatory behavior
Controlling the Growth of the Skin CommensalStaphylococcus epidermidisUsing D-Alanine Auxotrophy
Authors: Dodds David , Bose Jeffrey L. , Deng Ming-De , Dubé Gilles , Grossman Trudy , Kaiser Alaina , Kulkarni Kashmira , Leger Roger , Mootien-Boyd Sara , Munivar Azim , Oh Julia , Pestrak Matthew , Rajpura Komal , Tikhonov Alex , Turecek Traci , Whitfill Travis 
Published: March 2020

ABSTRACTUsing live microbes as therapeutic candidates is a strategy that has gained traction across multiple therapeutic areas. In the skin, commensal microorganisms play a crucial role in maintaining skin barrier function, homeostasis, and cutaneous immunity. Alterations of the homeostatic skin microbiome are associated with a number of skin diseases. Here, we present the design of an engineered commensal organism,Staphylococcus epidermidis, for use as a live biotherapeutic product (LBP) candidate for skin diseases. The development of novel bacterial strains whose growth can be controlled without the use of antibiotics, or genetic elements conferring antibiotic resistance, enables modulation of therapeutic exposure and improves safety. We therefore constructed an auxotrophic strain ofS. epidermidisthat requires exogenously supplied D-alanine. TheS. epidermidisstrain, NRRL B-4268 Δalr1Δalr2Δdat(SEΔΔΔ) contains deletions of three biosynthetic genes: two alanine racemase genes,alr1andalr2(SE1674 and SE1079), and the D-alanine aminotransferase gene,dat(SE1423). These three deletions restricted growth in D-alanine deficient media, pooled human blood, and skin. In the presence of D-alanine, SEΔΔΔcolonized and increased expression of human β-defensin 2 in cultured human skin modelsin vitro. SEΔΔΔ, showed a low propensity to revert to D-alanine prototrophy, and did not form biofilms on plasticin vitro. These studies support the potential safety and utility of SEΔΔΔas a live biotherapeutic strain whose growth can be controlled by D-alanine.