bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does Early Referral Lead to Early Repair? Quality Improvement in Cleft Care
Authors: Kondra Katelyn , Stanton Eloise , Jimenez Christian , Chen Kevin , Hammoudeh Jeffrey A. 
Published: May 2023

Background
Cleft lip and palate is the most common congenital defect of the head and neck, occurring in 1 of 700 live births. Diagnosis often occurs in utero by conventional or 3-dimensional ultrasound. Early cleft lip repair (ECLR) (<3 months of life) for unilateral cleft lip (UCL), regardless of cleft width, has been the mainstay of lip reconstruction at Children's Hospital Los Angeles since 2015. Historically, traditional lip repair (TLR) was performed at 3 to 6 months of life ± preoperative nasoalveolar molding (NAM). Previous publications highlight the benefits of ECLR, such as enhanced aesthetic outcomes, decreased revision rate, better weight gain, increased alveolar cleft approximation, cost savings of NAM, and improved parent satisfaction. Occasionally, parents are referred for prenatal consultations to discuss ECLR. This study evaluates timing of cleft diagnosis, preoperative surgical consultation, and referral patterns to validate whether prenatal diagnosis and prenatal consultation lead to ECLR.

Methods
Retrospective review evaluated patients who underwent ECLR versus TLR ± NAM from 2009 to 2020. Timing of repair, cleft diagnosis, and surgical consultation, as well as referral patterns, were abstracted. Inclusion criteria dictated: age < 3 months for ECLR or 3 to 6 months for TLR, no major comorbidities, and diagnosis of UCL without palatal involvement. Patients with bilateral cleft lip or craniofacial syndromes were excluded.

Results
Of 107 patients, 51 (47.7%) underwent ECLR whereas 56 underwent TLR (52.3%). Average age at surgery was 31.8 days of life for the ECLR cohort and 112 days of life for the TLR cohort. Furthermore, 70.1% of patients were diagnosed prenatally, yet only 5.6% of families had prenatal consults for lip repair, 100% of which underwent ECLR. Most patients were referred by pediatricians (72.9%). Significance was identified between incidence of prenatal consults and ECLR (P = 0.008). In addition, prenatal diagnosis was significantly correlated with incidence of ECLR (P = 0.027).

Conclusions
Our data demonstrate significance between prenatal diagnosis of UCL and prenatal surgical consultation with incidence of ECLR. Accordingly, we advocate for education to referring providers about ECLR and the potential for prenatal surgical consultation in the hopes that families may enjoy the myriad benefits of ECLR.
Outcomes of Local Versus Free Flaps for Reconstruction of the Proximal One-Third of the Leg
Authors: Kondra Katelyn , Roohani Idean , Carey Joseph N. 
Published: May 2023

Background
Reconstruction of the proximal one-third of the leg often requires soft tissue transfer to facilitate limb salvage. Tissue transfers are usually local or free flaps depending on wound dimensions, location, and surgeon preference. Historically, the proximal third of the leg was covered with pedicle flaps, but recently, we have used more free flaps in this position. Using data from a level 1 trauma center, we sought to evaluate outcomes of surgical management of proximal-third leg reconstruction across local and free flaps.

Methods
This is an institutional review board–approved, retrospective chart review undertaken at LAC + USC Medical Center from 2007 to 2021. Patient history, demographics, flap characteristics, Gustilo-Anderson fracture classification, and outcomes were collected and analyzed in an internal database. Outcomes of interest included flap failure rates, postoperative complications, and long-term ambulatory status.

Results
Among 394 lower extremity flaps placed, 122 flaps involved the proximal-third leg across 102 patients. Average age of patients was 42.8 ± 15.2 years; of note, the free flap cohort was significantly younger than the local flap cohort (P = 0.019). Ten local flaps suffered from infectious complications: osteomyelitis (n = 6) and hardware infection (n = 4), versus only 1 free flap that suffered from hardware infection; notably, these differences were not significant across cohorts. Free flaps had significantly more flap revisions (13.3%; P = 0.039) and overall flap complications (20.0%; P = 0.031) compared with local flaps; however, partial flap necrosis (4.9%) and flap loss (3.3%) were not significantly different across cohorts. Overall flap survival was 96.7%, and full ambulation was achieved in 42.2% of patients without significant differences across cohorts.

Conclusions
Our evaluation of proximal-third leg wounds demonstrates fewer infectious outcomes with free flaps compared with local flaps. There are multiple confounding variables; however, this finding may speak to the reliability of a robust free flap. Overall, there was no significant difference in patient comorbidities across flap cohorts with great overall flap survival. Ultimately, flap selection did not affect rates of flap necrosis, flap loss, or final ambulatory status.
HIV and Hepatitis C Virus-Related Disparities in Undergoing Emergency General Surgical Procedures in the United States, 2016-2019
Authors: Himmelstein Kathryn E.W. , Afif Iman N. , Beard Jessica H. , Tsai Alexander C. 
Published: May 2023

Objective:
To determine whether people living with HIV (PLWHIV) and people living with HCV (PLWHCV) experience inequities in receipt of emergency general surgery (EGS) care.

Summary Background Data:
PLWHIV and PLWHCV face discrimination in many domains; it is unknown whether this extends to receipt of EGS care.

Methods:
Using data from the 2016-2019 National Inpatient Sample, we examined 507,458 non-elective admissions of adults with indications for one of the seven highest-burden EGS procedures (partial colectomy, small-bowel resection, cholecystectomy, operative management of peptic ulcer disease, lysis of peritoneal adhesions, appendectomy, or laparotomy). Using logistic regression, we evaluated the association between HIV/HCV status and likelihood of undergoing one of these procedures, adjusting for demographic factors, comorbidities, and hospital characteristics. We also stratified analyses for the seven procedures separately.

Results:
After adjustment for covariates, PLWHIV had lower odds of undergoing an indicated EGS procedure (adjusted odds ratio [aOR], 0.81; 95% confidence interval [CI], 0.73-0.89), as did PLWHCV (aOR, 0.66; 95% CI, 0.63-0.70). PLWHIV had reduced odds of undergoing cholecystectomy (aOR, 0.68; 95% CI, 0.58-0.80). PLWHCV had lower odds of undergoing cholecystectomy (aOR, 0.57; 95% CI, 0.53-0.62) or appendectomy (aOR, 0.76; 95% CI, 0.59-0.98).

Conclusions:
People living with HIV and HCV are less likely than otherwise similar patients to undergo EGS procedures. Further efforts are warranted to ensure equitable access to EGS care for PLWHIV and PLWHCV.
Going for Broke
Authors: Drezdzon Melissa K , Cowley Norah J , Sweeney Daniel P , Peterson Carrie Y , Ridolfi Timothy J , Ludwig Kirk A , Evans Douglas B , Calata Jed F 
Published: May 2023

Objective:
Provide a direct comparison of first-year general surgery resident stipends across states and major cities, using the Cost-of-Living Index (COLI) to determine stipend value.

Summary of Background Data:
Financial challenges are among residents’ top sources of stress, and this may be exacerbated in areas with high costs of living. A 2021 survey found that the mean first-year medical resident stipend increased by 0.6%, or $358, from 2020 to 2021 and only 33% of institutions used cost-of-living to determine annual resident stipend adjustments.

Methods:
An AMA database was used to identify accredited general surgery residency programs. 2021-2022 stipend data for first-year general surgery positions was obtained, then data was grouped by state and major city and averaged. Major cities were defined as cities with greater than four programs.
A direct comparison of stipends was performed using the COLI.

Results:
Stipend data was available for 337 of 346 general surgery programs. The national average first-year residency stipend was $60,064±$4,233. The average COLI-adjusted stipend was $57,090±$5,742, with a value loss of -$3,493, or 5%.
For major cities, the average stipend was $63,383±$4,524 and average COLI-adjusted stipend was $46,929±$8,383, with an average value loss of -$16,454, or 26%.

Conclusion:
The financial burdens that residents face cannot be overlooked, and cost of living has a meaningful impact on resident stipend value. Current GME compensation structure limits federal and institutional capacity to adjust for cost of living and creates an insulated market in which residents are under-compensated.
Removal of AMR plasmids using a mobile, broad host-range CRISPR-Cas9 delivery tool
Authors: Sünderhauf David , Klümper Uli , Pursey Elizabeth , Westra Edze R. , Gaze William H. , van Houte Stineke 
Published: May 2023

Graphical Abstract
A broad host-range CRISPR-Cas9 delivery tool was developed and used to conjugatively remove antimicrobial resistance (AMR) plasmids (top) and protect a series of coliform and Pseudomonas isolates from AMR plasmid uptake (bottom).
HIV VIRAL SUPPRESSION AND ASSOCIATED FACTORS AMONG CHILDREN AND ADOLESCENTS ON A DOLUTEGRAVIR (DTG) BASED ANTIRETROVIRAL REGIMEN IN TANZANIA MAINLAND
Authors: Maghembe Abdallah Abtwalibe , Boer Marion Sumari-de , Marikias Godbless , Amour Caroline , Mahande Michael Johnson 
Published: May 2023

AbstractIntroductionAntiretroviral therapy (ART) reduces morbidity and mortality due to human immunodeficiency virus (HIV) infection. The complexity and time-consuming processes, particularly in drug approvals, have contributed to a major challenge to the ongoing success of antiretroviral treatment programs among children and adolescents. In 2019, Tanzania adopted DTG as a first-, second-line and third-line treatment for CALHIV on ART after being approved by the World Health Organisation (WHO). DTG treatment has highly potent antiviral activity, a high genetic barrier to resistance, and a high safety profile. This study aimed to determine HIV viral suppression and associated factors among CALHIV on DTG-based ART in Tanzania Mainland.MethodsThis was a retrospective cohort analysis among children and adolescents living with HIV who were on a DTG-based regimen in Tanzania Mainland between 2019 and 2021. The study utilized routinely collected data from Tanzania Care and Treatment Centres (CTC). We analysed data using STATA version 15 software. We calculated the prevalence of viral suppression by taking the number of children and adolescents with <1000 copies/ml overall study participants. A mixed effect generalized linear model with Poisson distribution and log link function with robust estimator determined the factors associated with HIV viral suppression on a DTG-based regimen.ResultsA total of 63,453 CALHIV on a DTG-based regimen were analysed. The proportion of viral suppression was 91.64%. Overall, 66.19% of previously unsuppressed individuals became suppressed and 88.45% of previously suppressed remained suppressed. Factors leading to lower chances of viral suppression were age 10-14 years (aRR: 0.98; 95%CI: 0.97-0.99), previously unsuppressed prior to starting DTG (aRR: 0.92; 95%CI: 0.91-0.93), duration on ART more than 24 months (aRR: 0.96; 95%CI: 0.94-0.97), not retained in care (aRR: 0.83; 95% CI: 0.77-0.89), severe malnutrition (aRR:0.77; 95%CI: 0.69-0.94) and coastal zone (aRR: 0.98; 95% CI: 0.96-0.99), while those in WHO stage I (aRR: 1.03; 95%CI: 1.01-1.04) and ever received a multi-month prescription (aRR: 1.25; 95% CI: 1.23-1.28) had a higher chance of viral suppression.ConclusionsThe findings support the broad use of DTG-based regimens for eligible CALHIV. Especially those in baseline WHO stage I and those who received the multi-month prescriptions were more likely to achieve viral load suppression. Programs should improve strategies to maintain CALHIV retention in care with interventions like the promotion of teen clubs and teams.
Proteomic Specificity of Soft Contact Lenses for Tear Protein Sampling
Authors: Roden Robert K. , Jiang Fangfang , Zuniga Nathan , Nitz Alyssa , Burlett Rebecca S. , Wright Joshua C. , Shelton Caleb , Reed Alex , Latham Samantha , Roper Connor O. , Patil Leena M. , Ackroyd P. Christine , Payne Samuel H. , Price John C. , Christensen Kenneth A. 
Published: May 2023

AbstractSoft contact lenses (SCLs) have recently been introduced as an alternative method for human tear protein sampling. However, SCLs are available in a variety of chemical compositions which affect protein binding specificity. Here we analyzed 8 different SCL materials to identify an optimal lens for tear protein sampling. Polymer contamination, mass spectrometry (MS) sample preparation method, total protein capture, individual protein specificity, and SCL cost were all assessed. Using a filter-aided sample prep (FASP) method with 4M guanidine for protein removal, only etafilcon A and verofilcon A did not have significant polymer contamination. Polymer was successfully removed using phosphate buffered saline (PBS) with S-Trap columns for all SCL materials, though yielding a slightly lower number of protein identifications per sample. Minor quantitative differences were observed between SCL materials. However, we also saw significant intersubject variation in protein abundance. Of all the assessed SCL materials, verofilcon A lenses yielded the most total protein while comfilcon A and senofilcon A had the least protein variability. As a newly released daily disposable modality (Precision 1, Alcon), verofilcon A has one of the longest predictable production schedules and one of the lowest costs per lens, making it beneficial for large-scale experiments and diagnostics. Furthermore, we demonstrate how protein binding bias with SCL tear sampling is useful for intra-experiment normalization. Overall, these experiments have led us to optimize our previous protocol for SCL tear protein sampling, highlighting important differences between SCL materials and identifying etafilcon A and verofilcon A as optimal materials for tear protein sampling.Abstract Figure
Inferior vena cava ultrasoundversuspassive leg raising test in guiding fluid administration in surgical patients prior to spinal anaesthesia: a post-hoc analysis of the ProCRHYSA randomized trial
Authors: Ceruti Samuele , Glotta Andrea , Favre Mathieu , Tasciotti Edoardo , Bona Giovanni , Petrusic Antonietta , Borgeat Alain , Aguirre José , Saporito Andrea 
Published: May 2023

ABSTRACTBackgroundSpinal anaesthesia is commonly used for many surgical procedures. One of its potential complications is arterial hypotension, which is nowadays prevented by an empirical fluid administration without any hemodynamic status assessment. However, this practice could increase the risk of volume overload in cardiovascular high-risk patients. Two non-invasive tests are performed to identify fluid-responsiveness: the Inferior Vena Cava Ultrasound (IVCUS) and the Passive Leg Raising Test (PLRT). Aim of this post-hoc analysis was to compare these two methods in spontaneous-breathing patients to assess fluid responsiveness before spinal anaesthesia. Primary outcome was to analyze the incidence of arterial hypotension after spinal anaesthesia in elective surgery patients. Secondary endpoints compared the total fluids amount, the vasoactive drugs administered and the time needed to accomplish the whole procedure in both groups.ResultsThe patients analyzed were 132 in the IVCUS group and 148 in the PLRT group; 39.6% of all patients developed arterial hypotension after spinal anaesthesia, 34.8% in the IVCUS group and 43.9% in the PLRT group (Chi-square 2.39, df = 1, p = 0.77). The mean total fluids amount was 794 ± 592 ml; 925 ± 631 ml for IVCUS group and 678 ± 529 ml for PLRT group (p < 0.001). Patients needed vasoactive drugs to restore normal arterial pressure were 18.2% of total, 15% in the IVCUS group and 20% in the PLRT group (p = 0.136). The mean time required to complete the entire procedure was 52 ± 18 min, 48 ± 10 min in the IVCUS group and 56 ± 13 min in the PLRT group (p < 0.001). Complications or out of protocol treatment were registered in 4.6% patients.ConclusionsFluid responsiveness assessment in spontaneous breathing patients before spinal anaesthesia could potentially prevent the risk of post-spinal hypotension. In elective surgery, IVCUS could be an accurate method to guide fluid administration in patients undergoing spinal anaesthesia, reducing the incidence of post-spinal hypotension when compared to PLRT.
Dissecting Symptom-linked Dimensions of Resting-State Electroencephalographic Functional Connectivity in Autism with Contrastive Learning
Authors: Tong Xiaoyu , Xie Hua , Fonzo Gregory A. , Zhao Kanhao , Satterthwaite Theodore D. , Carlisle Nancy , Zhang Yu 
Published: May 2023

AbstractAutism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized bysocial interaction deficits, communication difficulties, andrestricted/repetitive behaviors or fixated interests. Despite its high prevalence, development of effective therapy for ASD is hindered by its symptomatic and neurophysiological heterogeneities. To collectively dissect the ASD heterogeneity in neurophysiology and symptoms, we develop a new analytical framework combining contrastive learning and sparse canonical correlation analysis to identify resting-state EEG connectivity dimensions linked to ASD behavioral symptoms within 392 ASD samples. Two dimensions are successfully identified, showing significant correlations with social/communication deficits (r = 0.70) and restricted/repetitive behaviors (r = 0.45), respectively. We confirm the robustness of these dimensions through cross-validation and further demonstrate their generalizability using an independent dataset of 223 ASD samples. Our results reveal that the right inferior parietal lobe is the core region displaying EEG activity associated with restricted/repetitive behaviors, and functional connectivity between the left angular gyrus and the right middle temporal gyrus is a promising biomarker of social/communication deficits. Overall, these findings provide a promising avenue to parse ASD heterogeneity with high clinical translatability, paving the way for treatment development and precision medicine for ASD.
Dorsal and median raphe neuronal firing dynamics characterized by non-linear metrics
Authors: Rognoni Claudia Pascovich , Serantes Diego , Rodriguez Alejo , Mateos Diego , González Joaqúın , Gallo Diego , Rivas Mayda , Devera Andrea , Lagos Patricia , Rubido Nicolás , Torterolo Pablo 
Published: May 2023

AbstractThe dorsal (DRN) and median (MRN) raphe are the main serotonergic nuclei, being implicated in sleep and mood regulation. The DRN is mainly serotonergic, where neurons have regular spiking activity, slow firing rate (FR), and long action potential duration (APD). The MRN is divided in a median serotonergic region and a paramedian region, containing principally GABAergic neurons, resulting in more diverse neurochemical and electrophysiological features. In the present study, we aimed to enrich the characterization of the raphe nuclei neurons by using non-linear metrics. This was done by analyzing the neuronal basal firing profile in both nuclei of urethane-anesthetized rats using Ordinal Patterns (OP) Entropy, Bins Entropy, and Permutation Lempel-Ziv Complexity (PLZC). In a first step, we found that typical linear metrics – such as FR, coefficient of variation (CV), and APD – fail to distinguish between MRN and DRN neurons, while OP entropy is significantly different between these nuclei. We also found that the FR has a strong linear relationship with CV, Bins Entropy, and PLZC. Similarly, CV has a strong correlation with FR and Bins Entropy, whereas PLZC shows a strong linear fit with Bins Entropy. However, OP Entropy has either a weak or no linear relationship with the rest of the metrics tested, suggesting that OP Entropy is a good metric to differentiate neuronal firing profiles. In a second step, we studied how these metrics are affected by the oscillatory properties of the firing patterns. We found that all metrics are sensitive to rhythmicity – with the exception of OP Entropy. Again, this highlights OP Entropy as a powerful and useful quantity for the characterization of neuronal discharge patterns.
Triphasic production of IFNγ by innate and adaptive lymphocytes following influenza A virus infection
Authors: Finney George E , Hargrave Kerrie E , Pingen Marieke , Purnell Thomas , Todd David , MacDonald Freya , Worrell Julie C , MacLeod Megan KL 
Published: May 2023

AbstractInterferon gamma (IFNγ) is a potent antiviral cytokine that can be produced by many innate and adaptive immune cells during infection. Currently, our understanding of which cells produce IFNγand where they are located at different stages of an infection are limited. We have used reporter mice to investigatein vivoexpression of IFNγin the lung and secondary lymphoid organs during and following influenza A virus (IAV) infection. We observed a triphasic production of IFNγexpression. Unconventional T cells and innate lymphoid cells, particularly NK cells, were the dominant producers of early IFNγ, while CD4 and CD8 T cells were the main producers by day 10 post-infection. Following viral clearance, some memory CD4 and CD8 T cells continued to produce IFNγin the lungs and draining lymph node. Interestingly, IFNγproduction by lymph node Natural Killer (NK), NKT and innate lymphoid 1 cells also continued to be above naïve levels, suggesting memory-like phenotypes for these cells. Analysis of the localisation of IFNγ+ memory CD4 and CD8 T cells demonstrated that cytokine+ T cells were located near airways and in the lung parenchyma. Following a second IAV challenge, lung IAV specific CD8 T cells rapidly increased their expression of IFNγwhile CD4 T cells in the draining lymph node increased their IFNγresponse. Together, these data suggest that IFNγproduction fluctuates based on cellular source and location, both of which could impact subsequent immune responses.
Pharmaceutical agent cetylpyridinium chloride inhibits immune mast cell function by interfering with calcium mobilization
Authors: Obeng Bright , Potts Christian M. , West Bailey E. , Burnell John E. , Fleming Patrick J. , Shim Juyoung K. , Kinney Marissa S. , Ledue Emily L. , Sangroula Suraj , Baez Vazquez Alan Y. , Gosse Julie A. 
Published: May 2023

AbstractCetylpyridinium chloride (CPC) is an antimicrobial used in numerous personal care and janitorial products and food for human consumption at millimolar concentrations. Minimal information exists on the eukaryotic toxicology of CPC. We have investigated the effects of CPC on signal transduction of the immune cell type mast cells. Here, we show that CPC inhibits the mast cell function degranulation with antigen dose-dependence and at non-cytotoxic doses ∼1000-fold lower than concentrations in consumer products. Previously we showed that CPC disrupts phosphatidylinositol 4,5-bisphosphate, a signaling lipid critical for store-operated Ca2+entry (SOCE), which mediates degranulation. Our results indicate that CPC inhibits antigen-stimulated SOCE: CPC restricts Ca2+efflux from endoplasmic reticulum, reduces Ca2+uptake into mitochondria, and dampens Ca2+flow through plasma membrane channels. While inhibition of Ca2+channel function can be caused by alteration of plasma membrane potential (PMP) and cytosolic pH, CPC does not affect PMP or pH. Inhibition of SOCE is known to depress microtubule polymerization, and here we show that CPC indeed dose-dependently shuts down formation of microtubule tracks.In vitrodata reveal that CPC inhibition of microtubules is not due to direct CPC interference with tubulin. In summary, CPC is a signaling toxicant that targets Ca2+mobilization.