bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving Billing and Collections in a High-Volume Pediatric Surgery Practice: Denials-Based Approach
Authors: Ryan Mark L , Mutore Kevin T , DeLeon Jennifer , Gillory Lauren , Chung Dai H , Pandya Samir 
Published: February 2023

Introduction:
Despite minimal coding and billing training, surgeons are frequently tasked with both in clinical practice. This often results in denials for reimbursement based upon incorrect or insufficient documentation, and reduced collections for work performed. We sought to evaluate how to correct these deficits while improving reimbursement for the most frequently rejected procedures at a high-volume academic center.

Methods:
Hospital billing data was analyzed for a four-year period (2018-2021) to determine the CPT® code denials with the largest overall cost. The denials were then stratified according to payor, reason for denial, and preventability. Assigned ICD-10 codes were categorized based on specificity as related to the procedure. The distribution of denials according to ICD-10 specificity was evaluated using the Chi-Squared test.

Results:
8,833 denials totaling $11,009,108 in billing were noted over the study period. The CPT® code 44970 (laparoscopic appendectomy) was the code associated with the largest financial impact, representing 12.8% of the total denied amount ($1.41M). Of the 823 denials for CPT® 44970, 93.3% were associated with nonspecific ICD-10 codes, whereas only 42.0% had been associated with procedure-specific ICD-10 codes. Of the patients with nonspecific codes, 80.7% of denials were due to criteria that could be remedied with supplemental information or timely filing, representing $1,059,968 in collections.

Conclusions:
This is the first study to systematically evaluate a pathway for using denial data to improve collections for work performed at a high-volume academic pediatric surgery practice. Using this methodology, targets for improvement in coding and/or documentation can be identified to improve the financial performance of a surgical department. This study also provides evidence that association with nonspecific diagnostic codes is correlated with initial denial of payment by insurance companies.
Electroconvulsive Therapy Anesthetic Choice and Clinical Outcomes
Authors: Li Kevin J. , Slama Natalie E. , Hirschtritt Matthew E. , Anshu Prachi , Iturralde Esti 
Published: February 2023

Objective
Etomidate and methohexital are the 2 commonly used anesthetics for electroconvulsive therapy (ECT) in the United States. The objective of this study was to examine how anesthetic choice between etomidate and methohexital is associated with real-world clinical outcomes.

Methods
This naturalistic retrospective cohort study examined longitudinal electronic health records for 495 adult patients who received 2 or more ECT treatments from 2010 to 2019 in Kaiser Permanente North California, a large integrated health care system. Study outcomes included 12-month posttreatment depression remission as measured by the 9-item Patient Health Questionnaire, psychiatric and all-cause emergency department visits, and psychiatric and all-cause hospitalizations.

Results
Anesthetic choice was not significantly related to depression severity, emergency department visits, or psychiatric hospitalizations at 12 months after completing ECT. In exploratory analyses, we found that etomidate compared with methohexital was associated with higher rates of patient discomfort adverse effects—postictal agitation, phlebitis, and myoclonus (2.4% vs 0.4%; P < 0.001).

Conclusions
We present the first large comparison of etomidate and methohexital as anesthetics for ECT and their associations with real-world outcomes. Our study showed no significant difference on depression remission, emergency department visits, or hospitalizations 12-months posttreatment. Thus, clinicians should focus on other patient or treatment characteristics when deciding on anesthetics for ECT. Further investigation is needed to confirm our exploratory findings that etomidate use was correlated with a higher rate of patient discomfort adverse effects relative to methohexital.
Wilms tumor mutational subclasses converge to driveCCND2overexpression
Authors: Xu Lin , Desai Kavita , Kim Jiwoong , Zhou Qinbo , Guo Lei , Xiao Xue , Zhang Yanfeng , Zhou Li , Yuksel Aysen , Catchpoole Daniel R. , Amatruda James F. , Chen Kenneth S. 
Published: February 2023

ABSTRACTWilms tumor, the most common kidney cancer in pediatrics, arises from embryonic renal progenitors. Although many patients are cured with multimodal therapy, outcomes remain poor for those with high-risk features. Recent sequencing efforts have provided few biological or clinically actionable insights. Here, we performed DNA and RNA sequencing on 94 Wilms tumors to understand how Wilms tumor mutations transform the transcriptome to arrest differentiation and drive proliferation. We show that most Wilms tumor mutations fall into four classes, each with unique transcriptional signatures: microRNA processing, MYCN activation, chromatin remodeling, and kidney development. In particular, the microRNA processing enzymeDROSHAis one of the most commonly mutated genes in Wilms tumor. We show thatDROSHAmutations impair pri-microRNA cleavage, de-repress microRNA target genes, halt differentiation, and overexpress cyclin D2 (CCND2). Several mutational classes converge to driveCCND2overexpression, which could render them susceptible to cell-cycle inhibitors.SignificanceThrough integrated DNA and RNA sequencing analyses, we demonstrate novel genotype-transcriptome associations in Wilms tumors that converge to driveCCND2overexpression. Thus, although Wilms tumor mutations are not currently targetable, their effects on the transcriptome may be.
Occurrence of enteroparasites in vegetables commercialized in São Paulo, Brazil
Authors: Boccia Thais , Lopes Andrea Bento 
Published: February 2023

AbstractParasitic diseases constitute an important public health problem. Their transmission can occur by ingestion of water contaminated with human feces and/or parasitized animals, and by poorly washed fruits and vegetables. Considering the scarcity of national studies reporting the degree of contamination of vegetables, the present study investigated and compared the contamination of enteroparasites in 32 samples of each of the types: lettuce (Lactuca sativa) of the smooth and curly variety and watercress (Nasturtium officinale), commercialized in the city of São Paulo. For this purpose, the samples were washed with distilled water. The product of the washings was decanted in conical sedimentation vessels for 24 hours by the spontaneous sedimentation method, and the sediment was analyzed under an optical microscope. The results showed that of the 96 samples analyzed, 78 (82%) presented some parasitic form. Vegetables purchased from supermarkets and street markets showed a contamination rate of 80% (48/60) and 83% (30/36), respectively. The parasitic forms found were: 42%Ancylostoma splarvae,15.94% Ancylostoma speggs, 7.24%Ascaris speggs, 8.69%Enterobius speggs, 8.69 %Strongyloides splarvae, 7.24%Hymenolepis speggs, 5.79%Taenia speggs and 4.34%Entamoeba spcysts. These results demonstrate the need to develop a more efficient health education program aimed at horticulturists and vegetable handlers, with the intention of preventing the occurrence of these parasites, and further contamination of the population.
Executability and repeatability of a study setup using wearable and computerized technology to examine a wide range of physiological and cognitive functions of a patient outside hospital
Authors: Müller Kiti , Rautalin Ilari , Ahonen Lauri , Arola Anne , Henelius Andreas , Jokinen Hanna , Korpela Jussi , Korja Miikka , Martinez-Majander Nicolas , Mustonen Aaro , Paajanen Teemu , Pakarinen Satu , Pettersson Kati , Putaala Jukka , Sokka Laura , Tikka Tuomas , Virkkala Jussi 
Published: February 2023

ABSTRACTObjectivesReasons for a patient’s daily problems are often unclear as they are not systematically monitored in daily life. To remedy this, we designed a study protocol combining outpatient laboratory and home measurements. Feasibility of the protocol was evaluated by examining its executability and repeatability.ParticipantsSixteen patients undergoing neurosurgery for unruptured intracranial aneurysm (UIA), each acting as one’s own control.Study ProtocolTwo laboratory examinations followed by home recordings at 2 weeks pre- and 4-6 weeks postoperatively. In between a sole home recording at 3 weeks and 3 months postoperatively. Subjective health and performance data were gathered via an internet portal.MethodsLaboratory Day included computer-based cognitive tests on attention, working memory and executive functions. Electroencephalography (EEG), electrocardiography (ECG) and electrodermal activity (EDA) were recorded during the tests. A saccade test with electro-oculography (EOG) and event-related potentials (ERP) to emotionally loaded sounds were also done. First three home recordings included tablet-based cognitive tests, sleep polysomnography (PSG), ECG, and actigraphy; the 4thonly an actigraphy and sleep diary.Outcome measuresExecutability and repeatability of the protocol: Number of patients completing the study, success rate of carrying it out as planned, obtained data and patient feedback.ResultsIn 13 (81%) patients all data from home recordings was obtained as planned. In 11 (68%) patients the whole protocol was carried out as planned and in 3 partly. The time schedules required adjusting. Patients reported no discomfort from using wearable devices. Patients considered answering the internet-based health questionnaires cumbersome: all data was obtained only in 30%.ConclusionsMobile technologies are a tool kit from which to choose a clinically relevant combination to obtain objective data on a patient’s physical, physiologic, and cognitive performance outside hospital.StrengthsThe study consisted of a wide range of medical devices providing objective information on different physiologic functions and cognitive performance of a patient relevant for daily activities.The research examined executability, repeatability and patient compliance of a clinical study protocol and aspects relevant to obtaining clinically useful data.LimitationsParticipants did not have any chronic diseases that could affect especially home recording successThe study setup and protocol were not tested outside the home environment.The ability of patients to set up the different measurements independently and correctly was not tested.
A septo-hypothalamic-medullary circuit directs stress-induced analgesia
Authors: Shah Devanshi Piyush , Sharma Pallavi Raj , Agarwal Rachit , Barik Arnab 
Published: February 2023

AbstractStress is a potent modulator of pain. Specifically, acute stress due to physical restraint induces stress-induced analgesia (SIA). However, where and how acute stress and pain pathways interface in the brain are poorly understood. Here, we describe how the dorsal lateral septum (dLS), a forebrain limbic nucleus, facilitates SIA through its downstream targets in the lateral hypothalamic area (LHA) of mice. Taking advantage of transsynaptic viral-genetic, optogenetic, and chemogenetic techniques, we show that the dLS→LHA circuitry is sufficient to drive analgesia and is required for SIA. Further, our results reveal that the dLS→LHA pathway is opioid-dependent and modulates pain through the pro-nociceptive neurons in the rostral ventromedial medulla (RVM). Remarkably, we found that the inhibitory dLS neurons are recruited specifically when the mice struggle to escape under restraint and, in turn, inhibit excitatory LHA neurons. As a result, the RVM neurons downstream of LHA are disengaged, thus suppressing nociception. Together, we delineate a poly-synaptic pathway that can transform escape behavior in mice under restraint to acute stress into analgesia.
How the dominant reading direction changes parafoveal processing: A combined EEG/eye-tracking study
Authors: Huang Xin , Ng Hezul Tin-Yan , Lin Chien Ho , Yan Ming , Dimigen Olaf , Sommer Werner , Maurer Urs 
Published: February 2023

AbstractReading directions vary across writing systems. Through long-term experience readers adjust their visual systems to the dominant reading direction in their writing systems. However, little is known about the neural correlates underlying these adjustments because different writing systems do not just differ in reading direction, but also regarding visual and linguistic properties. Here, we took advantage that Chinese is read to different degrees in left-right or top-down directions in different regions. We investigated visual word processing in participants from Taiwan (both top-down and left-right directions) and from mainland China (only left-right direction). Combined EEG/eye tracking was used together with a saccade-contingent parafoveal preview manipulation to investigate neural correlates, while participants read 5-word lists. Fixation-related potentials (FRPs) showed a reduced late N1 effect (preview positivity), but this effect was modulated by the prior experience with a specific reading direction. Results replicate previous findings that valid previews facilitate visual word processing, as indicated by reduced FRP activation. Critically, the results indicate that this facilitation effect depends on experience with a given reading direction, suggesting a specific mechanism how cultural experience shapes the way people process visual information.
A Dual Function Antibody Conjugate Enabled Photoimmunotherapy Complements Fluorescence and Photoacoustic Imaging of Head and Neck Cancer Spheroids
Authors: Saad Mohammad A. , Grimaldo-Garcia Stacey , Sweeney Allison , Mallidi Srivalleesha , Hasan Tayyaba 
Published: February 2023

AbstractSeveral molecular-targeted imaging and therapeutic agents are in clinical trials for image-guided surgery and photoimmunotherapy (PIT) of head and neck cancers. In this context, we have previously reported the development, characterization, and specificity of a dual function antibody conjugate (DFAC) for multi-modal imaging and photoimmunotherapy (PIT) of EGFR over-expressing cancer cells. The DFAC reported previously and used in the present study, comprises of an EGFR targeted antibody – Cetuximab conjugated to Benzoporphyrin derivative (BPD) for fluorescence imaging and PIT, and a Si-centered naphthalocyanine dye for photoacoustic imaging. We report here the evaluation and performance of DFAC in detecting microscopic cancer spheroids by fluorescence and photoacoustic imaging along with their treatment by PIT. We demonstrate that while fluorescence imaging can detect spheroids with volumes greater than 0.049 mm3, photoacoustic imaging-based detection was possible even for the smallest spheroids (0.01 mm3), developed in the study. When subjected to PIT, the spheroids showed a dose-dependent response with smaller spheroids (0.01 and 0.018 mm3) showing a complete response with no recurrence when treated with 100 J/cm2. Together our results demonstrate the complementary imaging and treatment capacity of DFAC. This potentially enables fluorescence imaging to assess tumor presence on a macroscopic scale followed by photoacoustic imaging for delineating tumor margins guiding surgical resection and elimination of any residual microscopic disease by PIT, in a single intra-operative setting.
CD39+conventional CD4+T cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon CTLA-4 blockade
Authors: Bossio Sabrina N. , Abrate Carolina , Tosello Boari Jimena , Rodriguez Constanza , Canale Fernando P. , Ramello María C. , Richer Wilfrid , Rocha Dario , Sedlik Christine , Vincent-Salomon Anne , Borcoman Edith , Del Castillo Andres , Gruppi Adriana , Fernandez Elmer , Acosta Rodríguez Eva V. , Piaggio Eliane , Montes Carolina L. 
Published: February 2023

AbstractBackgroundConventional CD4+T (Tconv) lymphocytes play important roles in tumor immunity; however, their contribution to tumor elimination remains poorly understood.MethodsHere we describe a subset of Tconv cells characterized by the expression of CD39. The phenotype, the effector function and transcriptional profile of tumor-infiltrating CD39+Tconv lymphocytes from different mouse cancer models and breast cancer patients were studied by multiparametric flow cytometry and RNA sequencing. The impact of thein vivoCTLA-4 blockade on the tumor-infiltrating CD39+Tconv population was assessed in mice grafted with the immunogenic MC38 colorectal tumor. Overall survival was evaluated in a cohort of patients from the TCGA consortium.ResultsIn mouse cancer models, we observed that CD39+Tconv cells accumulated in tumors as they grew but were absent in lymphoid organs. Compared to tumor CD39−counterparts, CD39+Tconv cells exhibited a cytotoxic and exhausted signature at the transcriptomic level, confirmed by high protein expression of inhibitory receptors and transcription factors related to the exhaustion phenotype. Additionally, CD39+Tconv cells showed increased production of IFN gamma, granzyme B, perforin and CD107a expression, but reduced production of TNF.In vivoCTLA-4 blockade induced the expansion of tumor CD39+Tconv cells, which maintained their cytotoxic and exhausted features. In breast cancer patients, CD39+Tconv cells were found in tumors and in metastatic lymph nodes but were less frequent in adjacent non-tumoral mammary tissue and not detected in non-metastatic lymph nodes and blood. Human tumor CD39+Tconv cells constituted a heterogeneous cell population with features of exhaustion, impaired TNF production, and high expression of inhibitory receptors and CD107a. We found that high CD4 and ENTPD1 (CD39) gene expression in human tumor tissues correlated with a higher overall survival rate in breast cancer patients.ConclusionsWe found that CD39 acts as a biomarker of Tconv cells with characteristics of both exhaustion and cytotoxic potential. CTLA-4 blockade expands CD39+CD4+T cells which may contribute to the reduction of tumor development. Discovering the role of CD39-expressing CD4+T cells in the tumor microenvironment should help design new strategies to manipulate them and improve the efficacy of current immunotherapies.
IL-15 synergizes with CD40 agonist antibodies to induce durable immunity against bladder cancer
Authors: Wong Jeffrey L. , Smith Patrick , Angulo-Lozano Juan , Ranti Daniel , Bochner Bernard H. , Sfakianos John P. , Horowitz Amir , Ravetch Jeffrey V. , Knorr David A. 
Published: February 2023

AbstractCD40 is a central co-stimulatory receptor implicated in the development of productive anti-tumor immune responses across multiple cancers, including bladder cancer. Despite strong preclinical rationale, systemic administration of therapeutic agonistic antibodies targeting the CD40 pathway have demonstrated dose limiting toxicities with minimal clinical activity to date, emphasizing an important need for optimized CD40-targeted approaches, including rational combination therapy strategies. Here, we describe an important role for the endogenous IL-15 pathway in contributing to the therapeutic activity of CD40 agonism in orthotopic bladder tumors, with upregulation of trans-presented IL-15/IL-15Rα surface complexes, particularly by cross-presenting cDC1s, and associated enrichment of activated CD8 T cells within the bladder tumor microenvironment. In bladder cancer patient samples, we identify DCs as the primary source of IL-15, however, they lack high levels of IL-15Rα at baseline. Using humanized immunocompetent orthotopic bladder tumor models, we demonstrate the ability to therapeutically augment this interaction through combined treatment with anti-CD40 agonist antibodies and exogenous IL-15, including the fully-human Fc-optimized antibody 2141-V11 currently in clinical development for the treatment of bladder cancer. Combination therapy enhances the crosstalk between Batf3-dependent cDC1s and CD8 T cells, driving robust primary anti-tumor activity and further stimulating long-term systemic anti-tumor memory responses associated with circulating memory-phenotype T and NK cell populations. Collectively, these data reveal an important role for IL-15 in mediating anti-tumor CD40 agonist responses in bladder cancer and provide key proof-of-concept for combined use of Fc-optimized anti-CD40 agonist antibodies and agents targeting the IL-15 pathway. These data support expansion of ongoing clinical studies evaluating anti-CD40 agonist antibodies and IL-15-based approaches to evaluate combinations of these promising therapeutics for the treatment of patients with bladder cancer.
EXPANSION OF ANTIGEN- SPECIFIC MEMORY CELLS AS A POTENTIAL BOOSTER FOR FOOD TOLERANCE INDUCTION
Authors: Pereira e Silva Airton , Marmello Bárbara Oliveira , Letícia Bentes Ana , Faccini Claudia Regina Josetti das Neves , Rodrigues Sónia Kristy Pinto Melo , Soares João Ricardo Almeida , Nicolau Campos Sylvia Maria , Teixeira Gerlinde Agate Platais Brasil 
Published: February 2023

ABSTRACTApproximately 3% of children in Western countries are diagnosed with peanut allergy, a likely lifelong disease. The preferred treatment for food allergy is allergen avoidance. However, oral immunotherapy is an FDA-approved treatment to re-induce tolerance, still, not all patients respond as expected. Thus, the aim of this work is to evaluate whether the association of an antigen-specific tolerogenic (oral tolerance) bystander effect can ameliorate the recovery of inflamed intestinal mucosa. Adult male C57BL/6 mice were divided into five groups, four of which were submitted to an intestinal inflammation induction protocol to peanuts. After sensitization, experimental groups were orally challenged with either peanuts or a hybrid diet (peanuts + mouse chow). In a second stage, groups were sensitized, challenged with peanuts, and then received either peanuts, hybrid diet, or ovalbumin chow during the recovery period of the inflamed mucosa. Results showed no changes in diet intake and body weight. Polyisotypic anti-peanut IgG and IgG1 were significantly increased in the serum from animals in allergic groups. The group that received the hybrid diet showed an increase in CD4+CD25+Foxp3+regulatory T cells, as well as in B220+CD3-CD27+memory B cells. Histology of the duodenum showed a decrease in intraepithelial leukocytes in animals who received hybrid diet. Together, our results show that when the tolerogen is added to a diet containing the allergen, it can ameliorate the induction of local inflammation. Simultaneously offering the allergen with a tolerated food increased the mucosal recovery due to the expansion of previously induced memory cells.