bluuebunny/crossref_metadata_2025_split huggingface dataset:
Out-of-Pocket Costs for Patients Undergoing Thyroid Surgery
Authors: Zheng Feibi , Huang Yongmei , Wright Jason , Kuo Jennifer H. 
Published: July 2021

Objective:
The aim of this study was to determine out-of-pocket costs (OOPC) in patients undergoing thyroidectomy for benign and malignant conditions in a commercially insured US population.

Summary Background Data:
Little is known about OOPC for thyroid surgery in the United States.

Methods:
Retrospective cohort study using claims of patients undergoing thyroidectomy from the IBM Watson Marketscan database from 2008 to 2017. OOPCs accrued from 90 days before surgery to 360 days after thyroid surgery were quantified. Costs were divided into expenditures for inpatient care, outpatient care and outpatient drug costs and over three time periods: from 90 days preoperatively to 30 days post operatively, from 30 days post operatively to 90 days postoperatively, and from 90 days to 1 year after surgery.

Results:
A total of 45,971 commercially insured patients aged 18 to 95 years who underwent thyroidectomy were identified after excluding patients who changed coverage and patients on capitated plans. The median OOPC per patient in the study period of 90 days before surgery to 360 days after surgery was $2434 [interquartile range (IQR) $1273–$4226], the median insurance reimbursement was $15,520 (IQR $7653–$29,149). Patients undergoing thyroidectomy for malignant conditions had a median OOPC of $3019 (IQR $1596–$5021) compared to $2271 (IQR $1201–3954) for benign conditions (P < 0.0001).
Patients with preferred provider organization coverage had a median OOPC of $2624 (IQR $1458–$4358) compared to HMO patients with a median OOPC of $1529 (IQR $739 to 3058), and high deductible health plans with a median OOPC of $4265 (IQR $2788–$6210) (P < 0.0001).

Conclusion:
Despite commercial insurance coverage, patients face substantial OOPCs in the surgical management of thyroid disease in the United States.
Aligning Patient Acuity With Resource Intensity After Major Surgery
Authors: Loftus Tyler J. , Balch Jeremy A. , Ruppert Matthew M. , Tighe Patrick J. , Hogan William R. , Rashidi Parisa , Upchurch Gilbert R. , Bihorac Azra 
Published: July 2021

Objective:
Develop unifying definitions and paradigms for data-driven methods to augment postoperative resource intensity decisions.

Summary Background Data:
Postoperative level-of-care assignments and frequency of vital sign and laboratory measurements (ie, resource intensity) should align with patient acuity. Effective, data-driven decision-support platforms could improve value of care for millions of patients annually, but their development is hindered by the lack of salient definitions and paradigms.

Methods:
Embase, PubMed, and Web of Science were searched for articles describing patient acuity and resource intensity after inpatient surgery. Study quality was assessed using validated tools. Thirty-five studies were included and assimilated according to PRISMA guidelines.

Results:
Perioperative patient acuity is accurately represented by combinations of demographic, physiologic, and hospital-system variables as input features in models that capture complex, non-linear relationships. Intraoperative physiologic data enriche these representations. Triaging high-acuity patients to low-intensity care is associated with increased risk for mortality; triaging low-acuity patients to intensive care units (ICUs) has low value and imparts harm when other, valid requests for ICU admission are denied due to resource limitations, increasing their risk for unrecognized decompensation and failure-to-rescue. Providing high-intensity care for low-acuity patients may also confer harm through unnecessary testing and subsequent treatment of incidental findings, but there is insufficient evidence to evaluate this hypothesis. Compared with data-driven models, clinicians exhibit volatile performance in predicting complications and making postoperative resource intensity decisions.

Conclusion:
To optimize value, postoperative resource intensity decisions should align with precise, data-driven patient acuity assessments augmented by models that accurately represent complex, non-linear relationships among risk factors.
Neuromodulation in Super-refractory Status Epilepticus
Authors: Stavropoulos Ioannis , Pak Ho Lim , Valentin Antonio 
Published: July 2021

Summary:Status epilepticus (SE) is a severe condition that needs immediate pharmacological treatment to tackle brain damage and related side effects. In approximately 20% of cases, the standard treatment for SE does not control seizures, and the condition evolves to refractory SE. If refractory status epilepticus lasts more than 24 hours despite the use of anesthetic treatment, the condition is redefined as super-refractory SE (srSE). sRSE is a destructive condition, potentially to cause severe brain damage. In this review, we discuss the clinical neuromodulation techniques for controlling srSE when conventional treatments have failed: electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation, and deep brain stimulation. Data show that neuromodulation therapies can abort srSE in >80% of patients. However, no randomized, prospective, and controlled trials have been completed, and data are provided only by retrospective small case series and case reports with obvious inclination to publication bias. There is a need for further investigation into the use of neuromodulation techniques as an early treatment of srSE and to address whether an earlier intervention can prevent long-term complications.
New Horizons in Temporal Lobe Seizure Control
Authors: Velasco Ana L. , Saucedo-Alvarado Pablo E. , Alejandre-Sánchez Mariana , Guzmán-Jiménez Diana E. , González-Garcia Itzel , Velasco Francisco 
Published: July 2021

Summary:In patients with mesial temporal lobe epilepsy, high-frequency, low-amplitude electrical stimulation (ES) was applied during 3 weeks through contacts of intracranial electrodes that defined the epileptogenic zone. This subacute ES induced cessation of spontaneous seizures, decreased the number of EEG interictal spikes, caused a 10-fold increase in threshold to induce postdischarges, and showed a profound decrease in regional blood flow of the stimulated area in SPECT studies. Autoradiography analysis of surgical specimens from these patients demonstrated increased expression of benzodiazepine receptors and in gamma-aminobutyric acid content, particularly in the parahippocampal cortex. These observations provided evidence of a gamma-aminobutyric acid-mediated antiepileptic effect induced by ES. Several reports of long-term hippocampal ES through internalized neurostimulators have confirmed the antiepileptic effect on mesial temporal lobe–initiated seizures, with preservation of neuropsychological performance, in particular memory functions. The experience of the authors is that the response is optimal in patients without hippocampal sclerosis evidenced by MRI, whereas it is less significant and delayed in patients with hippocampal sclerosis. Other studies reported the best result stimulating through the contacts in the subiculum, the transition between the hippocampus and parahippocampal cortex, that usually escapes to the hippocampal sclerosis. Currently, the effect of ES directed at the subiculum and the parahippocampal cortex in patients with hippocampal sclerosis is under investigation.
Cathodal Transcranial Direct Current Stimulation in Refractory Epilepsy: A Noninvasive Neuromodulation Therapy
Authors: San-Juan Daniel 
Published: July 2021

Summary:
Epilepsy is a chronic disease of the brain that affects individuals of all ages and has a worldwide distribution. According to a 2006 World Health Organization report, 50 million people had epilepsy. Approximately 30% of people with epilepsy have refractory disease despite recent therapeutic developments. Consequently, new treatments are necessary. Transcranial direct current stimulation (tDCS) is a noninvasive method for cortical excitability modulation by subthreshold membrane depolarization or hyperpolarization (cathodal stimulation decreases cortical excitability, whereas anodal stimulation increases it), which has been shown to be safe, economical, and easy to use. The mechanism of action of tDCS is partially understood. Cathodal tDCS in vitro and in vivo animal studies have shown that direct current and cathodal tDCS can successfully induce suppression of epileptiform activity in EEG recordings. Cathodal tDCS has been used in heterogeneous clinical trials in pediatric and adult patients with refractory epilepsy and is well tolerated. A comprehensive review of the clinical trials based on their quality and biases shows evidence that cathodal tDCS in patients with epilepsy is potentially effective. However, additional randomized clinical trials are needed with other etiologies, special populations, additional concomitants therapies, long-term follow-up, and new parameters of stimulation.
The six steps of the F1-ATPase rotary catalytic cycle
Authors: Sobti Meghna , Ueno Hiroshi , Noji Hiroyuki , Stewart Alastair G. 
Published: July 2021

AbstractF1FoATP synthase interchanges phosphate transfer energy and proton motive force via a rotary catalysis mechanism. When isolated, its F1-ATPase catalytic core can hydrolyze ATP, rotating its γ rotor subunit. Although previous structural studies have contributed greatly to understanding rotary catalysis in F1, the structure of one major conformational state detected in single-molecule studies, termed the binding dwell state, has not yet been determined. Here, by exploiting a temperature-sensitive F1-ATPase mutant fromBacillusPS3, the structure of this binding dwell state was established together with that of the catalytic dwell state. Each state showed three catalytic β subunits in different conformations, providing the complete set of six β subunit conformational states taken up during catalysis cycle. These structures provide molecular details for the power-stroke conformational change that occurs upon ATP binding and induces a ~80° γ subunit rotation, as well as a second torque-generating conformational change, triggered by hydrolysis and product release, that produces a ~40° rotation. This study also identifies a putative phosphate-releasing tunnel that indicates how ADP and phosphate releasing steps are coordinated. Overall these findings provide a structural basis for the entire F1-ATPase rotary catalysis cycle.
Anatomically informed multi-level fiber tractography
Authors: Zhylka Andrey , Leemans Alexander , Pluim Josien , De Luca Alberto 
Published: July 2021

AbstractDiffusion weighted MR imaging can assist preoperative planning by reconstructing the trajectory of eloquent fiber pathways. A common task is the delineation of the corticospinal tract in its full extent because lesions to this bundle can severely affect the quality of life. However, this is challenging as existing tractography algorithms typically produce either incomplete results or multiple false-positive tracts. In this work, we suggest a novel approach to fiber tractography that reconstructs multi-level structures by progressively taking into account previously unused fiber orientations. Anatomical priors are used in order to minimize the number of false-positive pathways. The devised method was evaluated on synthetic data with different noise levels. Additionally, it was tested on in-vivo data by reconstructing the corticospinal tract and it was compared to conventional deterministic and probabilistic approaches. The corticospinal tract reconstructed by our method includes lateral projections that could not be observed with deterministic methods, while avoiding spurious tracts reconstructed by probabilistic tractography. Furthermore, the proposed algorithm preserves the neuroanatomical topology of the pathways to a larger extent as compared to probabilistic tractography.
DoChaP: The Domain Change Presenter
Authors: Gal-Oz Shani T. , Haiat Nimrod , Eliyahu Dana , Shani Guy , Shay Tal 
Published: July 2021

AbstractAlternative RNA splicing results in multiple transcripts of the same gene, possibly encoding for different protein isoforms with different protein domains and functionalities. Whereas it is possible to manually determine the effect of a specific alternative splicing event on the domain composition of a particular encoded protein, the process requires the tedious integration of several data sources; it is therefore error prone and its implementation is not feasible for genome-wide characterization of domains affected by differential splicing. To fulfill the need for an automated solution, we developed the Domain Change Presenter (DoChaP), a web server for the visualization of the exon–domain association. DoChaP visualizes all transcripts of a given gene, the domains of the proteins that they encode, and the exons encoding each domain. The visualization enables a comparison between the transcripts and between the protein isoforms they encode for. The organization and visual presentation of the information makes the structural effect of each alternative splicing event on the protein structure easily identified. To enable a study of the conservation of the exon structure, alternative splicing, and the effect of alternative splicing on protein domains, DoChaP also facilitates an inter-species comparison of domain–exon associations. DoChaP thus provides a unique and easy-to-use visualization of the exon–domain association and its conservation between transcripts and orthologous genes and will facilitate the study of the functional effects of alternative splicing in health and disease.
An unconventional conductance is required for pacemaking of nigral dopamine neurons
Authors: Jehasse Kevin , Massotte Laurent , Hartmann Sebastian , Vitello Romain , Ringlet Sofian , Vitello Marie , Chua Han Chow , Pless Stephan A. , Engel Dominique , Liégeois Jean-François , Lakaye Bernard , Roeper Jochen , Seutin Vincent 
Published: July 2021

ABSTRACTAlthough several ionic mechanisms are known to control rate and regularity of the pacemaker in dopamine (DA) neurons from the substantia nigra pars compacta (SNc), a conductance essential for pacing has yet to be defined. Here we provide pharmacological evidence that pacemaking of SNc DA neurons is enabled by an unconventional conductance. We found that 1-(2,4-xylyl)guanidine (XG), an established blocker of gating pore currents in mutant voltage gated sodium channels, selectively stops pacemaking of DA SNc neurons and is without effect on the main pore of their voltage-gated channels. We isolated a voltage-dependent, non-inactivating XG-sensitive current of 20-25 pA which operates in the relevant subthreshold range and is carried by both Na+ and Cl- ions. While the molecular identity of this conductance remains to be determined, we show that this XG-sensitive current is crucial to sustain pacemaking in these neurons.
Data Augmentation Through Monte Carlo Arithmetic Leads to More Generalizable Classification in Connectomics
Authors: Kiar Gregory , Chatelain Yohan , Salari Ali , Evans Alan C. , Glatard Tristan 
Published: July 2021

Machine learning models are commonly applied to human brain imaging datasets in an effort to associate function or structure with behaviour, health, or other individual phenotypes. Such models often rely on low-dimensional maps generated by complex processing pipelines. However, the numerical instabilities inherent to pipelines limit the fidelity of these maps and introduce computational bias. Monte Carlo Arithmetic, a technique for introducing controlled amounts of numerical noise, was used to perturb a structural connectome estimation pipeline, ultimately producing a range of plausible networks for each sample. The variability in the perturbed networks was captured in an augmented dataset, which was then used for an age classification task. We found that resampling brain networks across a series of such numerically perturbed outcomes led to improved performance in all tested classifiers, preprocessing strategies, and dimensionality reduction techniques. Importantly, we find that this benefit does not hinge on a large number of perturbations, suggesting that even minimally perturbing a dataset adds meaningful variance which can be captured in the subsequently designed models.GRAPHICAL ABSTRACTThis paper demonstrates how Monte Carlo Arithmetic, a dataagnostic perturbation technique, can be used for dataset augmentation during the generation of structural connectomes and improve downstream phenotypic prediction.
Comparative genomics of peroxisome biogenesis proteins: making sense of the PEX mess
Authors: Jansen Renate L.M. , Molina Carlos Santana , van den Noort Marco , Devos Damien P. , van der Klei Ida J. 
Published: July 2021

AbstractPEX genes encode proteins involved in peroxisome biogenesis and proliferation. Using a comparative genomics approach, we clarify the evolutionary relationships between the 37 known PEX proteins in a representative set of eukaryotes, including all common model organisms, pathogenic unicellular eukaryotes and human. A large number of previously unknown PEX orthologs were identified. We analysed all PEX proteins, their conservation and domain architecture and defined the minimum set of PEX proteins that is required to make a peroxisome. The molecular processes in peroxisome biogenesis in different organisms were put into context, showing that peroxisomes are not static organelles in eukaryotic evolution. Organisms that lack peroxisomes still contain a few PEX proteins, which probably play a role in alternative processes. Finally, the relationships between PEX proteins of two large families, the Pex11 and Pex23 families, were clarified, thereby contributing to the understanding of their complicated and sometimes incorrect nomenclature. We provide an exhaustive overview of this important eukaryotic organelle.
Making an equal system equitable: Proposing a sex-adjusted MELDNa score for liver transplantation allocation
Authors: Sealock Julia M. , Ziogas Ioannis A. , Zhao Zhiguo , Ye Fei , Alexopoulos Sophoclis P. , Matsuoka Lea , Chen Guanhua , Davis Lea K. 
Published: July 2021

AbstractBackground & AimsLiver allocation is determined by the model for end-stage liver disease (MELD), a scoring system based on four laboratory measurements. During the MELD era, sex disparities in liver transplant have increased and there are no modifications to MELD based on sex. We use data from electronic health records (EHRs) to describe sex differences in MELD labs and propose a sex adjustment.MethodsWe extracted lab values for creatinine, International Normalized Ratio of prothrombin rate, bilirubin, and sodium from EHRs at Vanderbilt University Medical Center (VUMC) and the All of Us Research Project to determine sex differences in lab traits. We calculated MELDNa scores within liver transplant recipients, non-transplanted liver disease cases, and non-liver disease controls separately. To account for sex differences in lab traits in MELDNa scoring, we created a sex-adjusted MELDNa map which outputs adjusted female scores mapped to male scores of equal liver disease severity. Using waitlist data from the Liver Simulated Allocation Modeling, we conducted simulations to determine if the sex-adjusted scores reduced sex disparities.ResultsAll component MELDNa lab values and calculated MELDNa scores yielded significant sex differences within VUMC (n=623,931) and All of Us (n=56,715) resulting in MELDNa scoring that disadvantaged females who, despite greater decompensation traits, had lower MELDNa scores. In simulations, the sex-adjusted MELDNa score modestly increased female transplantation rate and decreased overall death.ConclusionsOur results demonstrate pervasive sex differences in all labs used in MELDNa scoring and highlight the need and utility of a sex-adjustment to the MELDNa protocol.Lay SummaryLiver transplant waitlist position is determined by a score called MELDNa, which is calculated using four laboratory values. Once on the waitlist, males are more likely to receive a transplant, while females are more likely to die or be removed due to illness. We demonstrate that all four laboratory values in the MELDNa score show significant sex differences that disadvantage females in liver transplant. We created a sex-adjusted score that increases female transplantation rate and decreases death among both sexes in simulations.
Statistical modeling for quality risk assessment of clinical trials: follow-up at the era of remote auditing
Authors: Koneswarakantha Björn , Ménard Timothé 
Published: July 2021

AbstractBackgroundAs investigator site audits have largely been conducted remotely during the COVID-19 pandemic, remote quality monitoring has gained some momentum. To further facilitate the conduct of remote Quality Assurance (QA) activities for clinical trials, we developed new quality indicators, building on a previously published statistical modeling methodology.MethodsWe modeled the risk of having an audit or inspection finding using historical audits and inspections data from 2011 - 2019. We used logistic regression to model finding risk for 4 clinical impact factor (CIF) categories: Safety Reporting, Data Integrity, Consent and Protecting Endpoints.ResultsWe could identify 15 interpretable factors influencing audit finding risk of 4 out of 5 CIF categories. They can be used to realistically predict differences in risk between 25 and 43% for different sites which suffice to rank sites by audit and inspection finding risk.ConclusionContinuous surveillance of the identified risk factors and resulting risk estimates could be used to complement remote QA strategies for clinical trials and help to manage audit targets and audit focus also in post-pandemic times.
Absence of SARS-CoV-2 antibodies in pre-pandemic plasma from children and adults in Vietnam
Authors: Van Vinh Chau Nguyen , Thanh Nhan Le Nguyen , Nguyet Lam Anh , Kha Tu Nguyen Thi , Thu Hong Nguyen Thi , Huy Man Dinh Nguyen , Bich Ty Dinh Thi , Truc Nhu Le Nguyen , Yen Lam Minh , Khanh Truong Huu , Quang Minh Ngo Ngoc , Han Ny Nguyen Thi , Anderson Danielle , Wang Lin-Fa , van Doorn H. Rogier , Hung Nguyen Thanh , Thanh Tran Tan , Thwaites Guy , Van Tan Le ,   OUCRU COVID-19 research group
Published: July 2021

AbstractWe tested pre-pandemic (2015-2019) plasma samples from 148 Vietnamese children, and 100 Vietnamese adults at high risk of zoonotic infections, for antibodies against SARS-CoV-2 nucleocapsid and spike proteins. None was positive, indicating no prior serological cross-reactivity with SARS-CoV-2 that might explain the low numbers of COVID-19 in Vietnam.