bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring Corporate Compliance through Cooperative Federalism: Trends in Multistate Settlements by State Attorneys General
Authors: Provost Colin , Dishman Elysa , Nolette Paul
Published: June 2022

Recent scholarship on U.S. regulatory federalism has tended to focus on conflict between the states and state resistance to federal initiatives. Less attention has been given to federal–state cooperation and how it affects regulatory enforcement. In this article, we examine intergovernmental cooperation in multistate lawsuits filed by state attorneys general to ascertain trends in multistate regulatory enforcement through litigation over time. We pay particular attention to the increasing use of compliance monitoring by both state and federal regulators, including through monitors independent of the regulated industries. Relying upon a dataset of legal settlements, scoping interviews, and two case studies of recent multistate litigation, we find that federal–state cooperation in multistate lawsuits has become more institutionalized over time. This increased cooperation has created a two-way street in which state and federal regulators often combine resources and learn from each other through the process of compliance monitoring.
Enforcing Hopelessness: Complicity, Dependence, and Organizing in Frontline Oil and Gas Communities
Authors: Malin Stephanie A , Kallman Meghan Elizabeth
Published: June 2022

Fossil fuel companies hold enormous political, economic, and knowledge production power. Recently, industry operators have pivoted from pushing climate denialism to campaigns aimed at individualizing responsibility for climate crisis. In this paper, we focus on one related outcome of such efforts – people’s experiences of complicity – here in the context of unconventional oil and gas (UOG) production. We ask: How do mobilized activists experience fossil fuel scapegoating, and what does it mean for their goals as they organize against UOG production? We show that even activists fighting UOG production feel complicit in fossil fuel production, and these feelings of complicity diminish their demands for UOG accountability. We argue that these outcomes have been especially pernicious in cultural contexts like that of the United States, where neoliberal ideologies are normalized, centering personal responsibility, individualization, and identification as consumers rather than citizens. We marshal an extensive qualitative dataset and advance a theory of complicity as a way to understand: a) how social movements intersect with neoliberalized patterns of life; b) how experiences of complicity affect activism; and c) how this may contribute to fossil fuel firms’ goals of undercutting organizing. We end by examining how a sub-set of activists works to dismantle this complicity narrative.
Risk of hypertension and treatment on out-of-hospital cardiac arrest incidence
Authors: Kim Jooyeong , Cho Sung-il , Park Jong-Hak , Song Juhyun , Ahn Sejoong , Cho Hanjin , Moon Sungwoo
Published: June 2022

Hypertension (HTN) is a high risk factor for major cardiovascular adverse events. This study aimed to investigate the effect of HTN risk on out-of-hospital cardiac arrest (OHCA) incidence and determine whether the effect of HTN on OHCA incidence differs according to antihypertensive medication.

This case-control study used the Korean Cardiac Arrest Resuscitation Consortium and Korean Community Health Survey (CHS). Cases were defined as emergency medical service-treated adult OHCA patients presumed to have a cardiac etiology from 2015 to 2017. Patients without information on HTN diagnosis were excluded from the study. The Korean CHS database's controls were matched at a 1:2 ratio with strata, including age, gender, and county of residence. Multivariable conditional logistic regression analysis was conducted to estimate HTN risk and antihypertensive treatment on OHCA incidence,

A total of 2633 OHCA patients and 5266 community-based controls were enrolled in this study. Among them, 1176 (44.7%) patients and 2049 (38.9%) controls were diagnosed with HTN. HTN was associated with an increased risk of OHCA (adjusted odds ratio [AOR]: 1.19 [1.07–1.32]). On comparing HTN with or without the antihypertensive treatment group with the non-HTN-diagnosed group (as a reference), the HTN without treatment group had the highest AOR (95% confidence interval) (3.41 [2.74–4.24]). The AOR in the HTN treatment group was reduced to that in the non-HTN-diagnosed group (0.96 [0.86–1.08]).

HTN increased OHCA risk, and the HTN without treatment group had the highest OHCA risk. Conversely, OHCA risk decreased to the non-HTN-diagnosed group level with HTN treatment.
Conservative treatment of gastric perforation after microwave ablation of a hepatocellular carcinoma
Authors: Roller J. , Zimmer V. , Bücker A. , Glanemann M. , Eisele R.M.
Published: June 2022

Rationale:

Microwave ablation (MWA) has been proven to be an efficient and safe method for local tumor control of liver tumors. Reported complications are rare, but include liver abscess, hematoma, pleural effusion, and occasional thermal injury of the adjacent colon. Intestinal perforation usually requires immediate surgical treatment to prevent generalized peritonitis and sepsis.

Patient concerns and diagnosis:

Herein, we describe a case of gastric perforation following percutaneous MWA for hepatocellular carcinoma as a bridging therapy prior to liver transplantation.

Interventions:

Due to the clinical condition of the patient, conservative treatment was considered sufficient. Nine months after MWA, successful liver transplantation followed. Intraoperative findings revealed a scar in the gastric wall with tight adhesions to the liver, requiring adhesiolysis and subsequent suturing. Postoperative recovery was uneventful.

Outcome:

At present, the patient is doing well. No further gastrointestinal events occurred.

Lesson:

To our knowledge, this is the first report of such a complication occurring after MWA. Moreover, in this case, the gastric perforation could be treated conservatively.
Nonintubated bronchoscopic interventions with high-flow nasal oxygen
Authors: Yie Jr-Chi , Lin Ching-Kai , Shih Chung-Chih , Li Ying-Tzu , Lin Wen-Ying , Cheng Ya-Jung
Published: June 2022

To determine the feasibility on maintaining oxygenation of high-flow nasal oxygenation (HFNO) with bispectral index-guided intravenous anesthesia for nonintubated interventional bronchoscopy (NIIB). If desaturation happens, the factors influencing intraprocedural desaturation were also analyzed.

This is a single-center retrospective study on patients receiving NIIB with HFNO and intravenous anesthesia guided by bispectral index levels to the depth of general anesthesia, which were between 40 and 60. Intraprocedural desaturation (SPO2 < 90%) and complications (bleeding, delayed discharge, unexpected admission) were collected. Factors affecting desaturation and complications were analyzed including patients’ factors (age, American Society of Anesthesiologists classification, body mass index [BMI]), procedural factors (procedural time, with or without use of cryoprobe), and setting (outpatient or hospitalized).

Records of 223 patients receiving NIIB were collected. The NIIB procedures time was 56.1 ± 26.8 minute. Sixty patients (26.9%) presented desaturation events. Higher BMI, but not procedure time or setting, was significantly associated with desaturation. The desaturation were resolved after relieving upper airway obstruction but 1 patient required bag–valve–mask ventilation to restore oxygenation. Accidental massive bleeding and intraprocedural desaturation during tracheal and bronchial recannulation with cryoprobes happened in 2 patients and 1 of them was admitted to intensive care unit.

HFNO is feasible to maintain oxygenation during NIIB only if there is effective upper airway management especially for patients with higher BMI. Longer procedural time and different setting did not affect the desaturation rate. Complications and unexpected admission were associated with the use of cryoprobes.
Randomized phase II study of nintedanib with or without pirfenidone in patients with idiopathic pulmonary fibrosis who experienced disease progression during prior pirfenidone administration
Authors: Ikeda Satoshi , Sekine Akimasa , Baba Tomohisa , Kato Terufumi , Katano Takuma , Tabata Erina , Shintani Ryota , Yamakawa Hideaki , Oda Tsuneyuki , Okuda Ryo , Kitamura Hideya , Iwasawa Tae , Takemura Tamiko , Ogura Takashi
Published: June 2022

Introduction:

A subgroup analysis of the CAPACITY and ASCEND trials showed that pirfenidone use beyond disease progression reduced the risk of subsequent forced vital capacity (FVC) decline and death. Our study aimed to compare the efficacy and safety of nintedanib with or without pirfenidone for patients with idiopathic pulmonary fibrosis (IPF) who experienced disease progression during previous pirfenidone therapy.

Methods:

In this randomized, open-label, selection design phase II trial, patients with IPF and a ≥5% relative decline in FVC within 6 months of the pirfenidone administration period were randomly assigned to nintedanib (switch group) or nintedanib plus pirfenidone (combination group). The primary endpoint was the incidence of a ≥5% relative decline in FVC or death during the first 6 months.

Results:

Only 7 patients were enrolled (4 in the switch group and 3 in the combination group). Although the switch group continued with nintedanib for 1 year or more, 2 patients (66.7%) in the combination group discontinued nintedanib within 6 months due to severe adverse events. Given the slow case registration and safety concerns in the combination group, the trial was terminated without extending the registration. The incidence of a ≥5% relative decline in FVC during the first 6 months was 50.0% in the switch group and 66.7% in the combination group. There were no deaths during the observation period.

Conclusions:

Clinical trials verifying the use of pirfenidone after disease progression in IPF may be difficult to enroll patients. Definitive conclusions on both safety and efficacy cannot be drawn from the results of this study alone.

Trial registration:

UMIN Clinical Trial Registry; registration number, UMIN000019436; date of first registration, 21/10/2015; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000022471.
Prophylactic octreotide for postoperative pancreatic fistula in patients with pancreatoduodenectomy
Authors: Yoon So Jeong , Lee Okjoo , Jung Ji Hye , Shin Sang Hyun , Heo Jin Seok , Han In Woong
Published: June 2022

Background:

Postoperative pancreatic fistula is one of the most critical complications following pancreatic surgery. This study aimed to evaluate the utility of selective prophylactic octreotide for patients at high risk of developing postoperative pancreatic fistula.

Methods:

From June 2019 to July 2020, 263 patients underwent pancreatoduodenectomy with pancreatojejunostomy at Samsung Medical Center. The individual fistula risk scores were calculated using a previously developed nomogram. The clinicopathological data of the patients were retrospectively reviewed.

Results:

There were 81 patients in the low-risk group and 182 patients in the high-risk group. No statistically significant differences were found in the rates of clinically relevant postoperative pancreatic fistula between octreotide group and the control group in all patients (15.0% vs 14.7%, P = .963) and in the high-risk group (16.1% vs 23.6%, P = .206). In risk factor analysis, postoperative octreotide was not an independent risk factor for clinically relevant pancreatic fistula in all patients and the high-risk group. Drain fluid amylase levels on the first postoperative day were significantly associated with clinically relevant postoperative pancreatic fistula, regardless of the individual risk.

Conclusions:

The selective use of octreotide, even in high-risk patients, showed no protective effect against pancreatic fistula. Therefore, the routine use of postoperative octreotide is not recommended.
Surgical management strategy for leiomyosarcoma of Zone I-II inferior vena cava
Authors: Tulahong Aisikeer , Tuxun Tuerhongjiang , Yao Gang , Fulati Xiapukati , Apaer Shadike , Anweier Nuerzhatijiang , Wu Jing , Aierken Amina , Zhao Jin-Ming , Bai Lei , Li Tao
Published: June 2022

Objectives:

Leiomyosarcoma of inferior vena cava (IVC) is a rare clinical entity with severe vascular involvement. Surgical management of leiomyosarcoma is still challenging.

Methods:

This a retrospective study of consecutive patients referred to our hospital from January 2017 to June 2019. Depending on the anatomical site of affected IVC, leiomyosarcomas were categorized into zone I-II. The clinical data including baseline information, surgical parameters, peri-operative management, short- and mid-term outcomes were observed.

Results:

Four patients with leiomyosarcoma of zone I-III underwent radical resection without intraoperative mortality. Prosthetic grafts were interpositioned in all patients to instruct vena cava. Renal vein reconstruction was perfumed in two patients due to involvement to renal veins. Median blood loss was 450 mL (200–600 mL), median operative time was 215 minutes (150–240 minutes). No Clavien-Dindo IIIa or higher complication was observed. No organ dysfunction and recurrence were observed with median follow-up of 25.5 months.

Conclusions:

Curative resection of zone I-II leiomyosarcoma is associated with longer survival in selected cases, en-bloc resection with complex vascular reconstruction could be considered.
Investigator initiated clinical trial to validate usefulness of specific system for endoscopic ultrasound guided hepaticogastrostomy (HG01) in malignant biliary obstruction (HG01)
Authors: Itonaga Masahiro , Kitano Masayuki , Isayama Hiroyuki , Takenaka Mamoru , Ogura Takeshi , Yamashita Yasunobu , Fujisawa Toshio , Minaga Kosuke , Okuda Atsushi , Shimokawa Toshio
Published: June 2022

Introduction:

Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is a novel drainage option for patients with an inaccessible papilla. Although EUS-HGS has clinical benefits in patients for whom endoscopic retrograde cholangiopancreatography (ERCP) has failed, the rates of adverse events (AEs) associated with EUS-HGS, such as bile peritonitis and stent migration, are higher than for other procedures. The development of a dedicated system for EUS-HGS is therefore desirable to reduce the rate of AEs. We developed a dedicated system for EUS-HGS (HG01 system) which is composed of a 19-gauge needle, 0.025-inch guidewire, a thin delivery system for tract dilation, and an antimigration metal stent. This study is designed to evaluate the efficacy and safety of EUS-HGS using the HG01 system in malignant biliary obstruction.

Methods/design:

This is a single-arm multicenter prospective study involving 40 patients across six tertiary centers in Japan. Patients with an unresectable malignant biliary obstruction in whom biliary drainage with ERCP failed, is not possible, or is very difficult will be registered in the study. The primary endpoint is the clinical success rate. The secondary endpoints are the technical success rate, procedure-related AE rate, procedure time, procedure success rate using only the HG01 system, stent patency rate, re-intervention success rate, re-intervention method, survival rate, and distance of movement of the stent position.

Discussion:

We expect use of the HG01 system to reduce the rate of AEs during EUS-HGS, especially bile leakage and stent migration. If the efficacy and safety of EUS-HGS using the HG01 system is confirmed in the present study, it is likely to be considered the first-choice device for use during EUS-HGS.
Malignant giant cell tumor of toe
Authors: Hashimoto Kazuhiko , Nishimura Shunji , Ito Tomohiko , Akagi Masao
Published: June 2022

Introduction:

A giant cell tumor of soft tissue (GCST) is a benign soft tissue tumor that often occurs subcutaneously in the extremities. Rare cases of malignant GCST have been reported, but its pathogenesis remains unclear.

Patients concerns:

We report a case of a 68-year-old man who noticed a painless mass on his second toe one and a half years ago. He visited the Department of Dermatology at our hospital. Magnetic resonance imaging revealed a soft tissue tumor, surrounding the distal aspect of the second toe.

Diagnosis:

A biopsy of the tumor was performed by a dermatologist, and it revealed a malignant giant cell tumor of the toe.

Interventions:

He was referred to our department and underwent lay amputation for wide-margin resection.

Outcomes:

No recurrence or metastasis was observed 5 years after treatment.

Conclusion

: Malignant GCST should be treated with wide-margin resection immediately after its diagnosis.
The Efficacy of Nurse-Performed Ultrasound Guidance Compared with the Conventional Cannulation Technique in Patients with Difficult Peripheral Intravenous Access: A Systematic Review
Authors: Anderssen Lisa Maria , Wang August Gabriel , Sofía Fjallheim Anna
Published: June 2022

Objective

The aim of this review is to highlight the efficacy of nurse-performed ultrasound guidance compared with the conventional cannulation technique in patients with difficult peripheral intravenous access.

Design

A systematic litterature review.

Data sources

The CINAHL and PubMed databases were searched for articles from the period 2011-2021.

Method

The following search words were used: peripheral intravenous AND ultrasonography OR ultrasound guided AND catheterization, peripheral/methods. The keyword catheterization, peripheral/methods was found via MeSH Terms (Medical Subject Headings) which PubMed recommended as keyword within the intervention of the conventional cannulation technique.

Results

2 out of 3 articles prove that success rate on the first attempt (primary outcome) was significantly higher in the nurse-performed ultrasound-guided technique compared with the conventional palpation technique. The results of the secondary outcomes; time consumption, complications, patient satisfaction and nurse satisfaction between the two groups proved to be heterogeneous.

Conclusion

Nurse-performed ultrasound guidance in hospital wards increases the success rate in patients with difficult peripheral intravenous access.
Assessment of benefits of Echo Workflow Solution: Findings from a two-step Delphi study
Authors: Boonyaratavej S. , Riccobene F. , Falahi F. , Franke J. , Solis J. , Lang R. M.
Published: June 2022

Objective

This study aimed to assess the clinical, operational, and economic benefits of Echo Workflow Solution comprising cardiac ultrasound systems and their advanced echo imaging tools; Ultrasound Workspace tools for advanced visualization and analysis; and the IntelliSpace Cardiovascular platform for image and information management and reporting.

Method

A modified Delphi method consisting of two rounds of queries was used to survey a panel of seven experts at geographically dispersed sites (Spain: 2, Thailand: 1, Saudi Arabia: 1, United Kingdom: 2, and USA: 1). Experts were identified via referral and selected based on experience with the solution. Both rounds of the Delphi process were conducted via a verbal or offline questionnaire between December 2021 and April 2022. Participants rated 14 attributes of the solution on a Likert Scale and added qualitative responses.

Results

Consensus was unanimous that the solution can enhance access to complete and longitudinal data needed for patient care decision-making; can lead to increased report consistency, measurement reproducibility and comparability; can help with better collaboration within the user’s organization, can help with saving report turnaround time and with improving time-to-detection and/or diagnosis.

The majority of respondents (86%) agreed that use of the Echo Workflow Solution can help increase confidence in diagnosis decision-making; can improve staff experience by providing single screen access to the patient data and lower cognitive load.

Conclusion

The study demonstrated that the Echo Workflow Solution can offer clinical and operational benefits. Responses indicated that the solution help with several aspects: reducing time to diagnosis, making it easier to accommodate emergency patients, providing time to perform more advanced studies, and/or increasing time spent with patients. Responses also indicated that the increased consistency and reproducibility of studies can potentially eliminate the need for unnecessary exams, which may result in a better patient experience and economic benefits for healthcare systems. The value of reproducibility, improved time to detection/diagnosis and increased confidence were particularly evident in complex cases and for patients requiring serial studies.
Deep learning system for brain image-aided diagnosis of multiple major mental disorders
Authors: Li Qingfeng , Wang Wengzheng , Guo Qian , Jiang Lijuan , Qiao Kaini , Hu Yang , Zhang Xiaochen , Wang Zhen , Peng Daihui , Fan Qing , Zhao Min , Fang Yiru , Wang Jijun , Qiu Hong , Wang Jinhong , Li Guanjun , Sheng Jianhua , Li Chunbo , Yang Zhi ,   the Psychiatric Imaging Consortium
Published: June 2022

The current clinical diagnosis of psychiatric disorders relies heavily on subjective assessment of symptoms. While neuroimaging has made an essential contribution to characterizing the brain of psychiatric disorders, it does not currently serve the clinical diagnosis of major psychiatric disorders. Here, we report a neuroimaging-aided diagnostic system for major psychiatric disorders designed for clinical needs. We developed novel deep learning networks with attentional mechanisms and applied them to a large-scale, single-center neuroimaging dataset containing four major psychiatric disorders and healthy groups (n=2490). Both cross-validation and extensive independent validation using multiple open-source datasets (n = 1972) showed that the system could accurately identify any one of the four diagnostic categories and healthy population from brain structural imaging. For the first time, we have constructed an automatic neuroimaging-aid diagnostic system that considers common issues in practice, such as co-morbid diagnoses and the discrimination between specific suspected diagnoses. Furthermore, real-world applications have validated the system’s effectiveness. These works contribute to the translation of brain research to objective diagnostic aids for psychiatric disorders.
AI-Assisted Chemical Probe Discovery for the Understudied Calcium-Calmodulin Dependent Kinase, PNCK
Authors: Essegian Derek J. , Chavez Valery , Khurshid Rabia , Merchan Jaime R. , Schürer Stephan C.
Published: June 2022

PNCK, or CAMK1b, is an understudied kinase of the calcium-calmodulin dependent kinase family which recently has been identified as a marker of cancer progression and survival in several large-scale multi-omics studies. The biology of PNCK and its relation to oncogenesis has also begun to be elucidated, with data suggesting various roles in DNA damage response, cell cycle control, apoptosis and HIF-1-alpha related pathways. To further explore PNCK as a clinical target, potent small-molecule molecular probes must be developed. Currently, there are no targeted small molecule inhibitors in pre-clinical or clinical studies for the CAMK family. Additionally, there exists no experimentally derived crystal structure for PNCK. We herein report a three-pronged chemical probe discovery campaign which utilized homology modeling, machine learning, virtual screening and molecular dynamics to identify small molecules with low-micromolar potency against PNCK activity from commercially available compound libraries. We report the first described inhibitor hit series for PNCK that will serve as the starting point for future medicinal chemistry efforts for hit-to-lead optimization of potent chemical probes.
An ensemble method for designing phage-based therapy against bacterial infections
Authors: Aggarwal Suchet , Dhall Anjali , Patiyal Sumeet , Choudhury Shubham , Arora Akanksha , Raghava Gajendra P.S.
Published: June 2022

Phage therapy is a viable alternative to antibiotics for treating microbial infections, particularly managing drug-resistant strains of bacteria. One of the major challenges in designing phage based therapy is to identify the most appropriate phage to treat a bacterial infection. In this study, an attempt has been made to predict phage-host interaction with high accuracy to identify the best virus for treating a bacterial infection. All models have been developed on a training dataset containing 826 phage host-interactions, whereas models have been evaluated on a validation dataset comprising 1201 phage-host interactions. Firstly, alignment based models have been developed using similarity between phage-phage (BLASTPhage), host-host (BLASTHost) and phage-CRISPR (CRISPRPred) where we achieved accuracy between 42.4%-66.2% for BLASTPhage, 55%-78.4% for BLASTHost, and 43.7%-80.2% for CRISPRPred at five taxonomic levels. Secondly, alignment free models have been developed using machine learning techniques. Thirdly, hybrid models have been developed by integrating alignment-free models and similarity-score where we achieved maximum performance of (60.6%-93.5%). Finally, an ensemble model has been developed that combines hybrid and alignment based model. Our ensemble model achieved highest accuracy of 67.9%, 80.6%, 85.5%, 90%, 93.5% at Genus, Family, Order, Class and Phylum levels, which is better than existing methods. In order to serve the scientific community we have developed a webserver named PhageTB and standalone software package (https://webs.iiitd.edu.in/raghava/phagetb/).

Key Points

Phage therapy provides an alternative to mange drug resistant strains of bacteria

Prediction bacterial strains that can be treated by a given phage

Alignment-based, alignment-free and ensemble models have been developed.

Prediction of appropriate phage/virus that can lyse a given strain of bacteria.

Webserver and standalone package provided to predict phage-host interactions.
Olfactory decoding is positively associated with ad libitum food intake in sated humans
Authors: Perszyk Emily E. , Davis Xue S. , Small Dana M.
Published: June 2022

The role of olfaction in eating behavior and body weight regulation is controversial. Here we used functional magnetic resonance imaging to test whether central olfactory coding is associated with internal state, food intake, and change in body weight over one year in healthy human adults. Since odor quality and category are coded across distributed neural patterns that are not discernible with traditional univariate analyses, we used multi-voxel pattern analyses to decode patterns of brain activation to food versus nonfood odors. We found that decoding accuracies in the piriform cortex and amygdala were greater in the sated compared to hungry state. Sated decoding accuracies in these and other regions were also associated with post-scan ad libitum food intake, but not with weight change. These findings demonstrate that the fidelity of olfactory decoding is influenced by internal state and is associated with immediate food intake, but not longer-term body weight regulation.
Universality in the Mechanical Behavior of Vertex Models for Biological Tissues
Authors: Damavandi Ojan Khatib , Arzash Sadjad , Lawson-Keister Elizabeth , Manning M. Lisa
Published: June 2022

Simple vertex models, where the cell shape is defined as a network of edges and vertices, have made useful predictions about the collective behavior of confluent biological tissues, including rigidity transitions. Quite a few different versions of vertex models have appeared in the literature, and they propose substantial differences in how the mechanical energy depends on vertex positions, yet all of them seem to make correct predictions. To understand how this is possible, we search for universality in the emergent mechanical behavior – including the shear modulus defined in the limit of zero strain rate and the viscoelastic response at finite strain rates – of six different vertex models. We identify a class of models with a well-defined shear modulus, and demonstrate that these models all exhibit a cross-over from a soft or floppy regime to a stiff regime. While the parameter that controls the crossover is different in each model, we find that the observed cell shape index (the ratio of the cell perimeter to the square root of the cell area) is a good observable order parameter for the crossover. We also find that the finite strain-rate viscoelastic response of all models exhibits a universal scaling with frequency, following the Zener model in the rigid phase and Burgers model in the fluid phase. This suggests there is a broad class of vertex models with universal mechanical features, and helps to explain why many different vertex models are able to robustly predict these features in experiments.
Simulation-Based Inference for Whole-Brain Network Modeling of Epilepsy using Deep Neural Density Estimators
Authors: Hashemi Meysam , Vattikonda Anirudh N. , Jha Jayant , Sip Viktor , Woodman Marmaduke M. , Bartolomei Fabrice , Jirsa Viktor K.
Published: June 2022

Whole-brain network modeling of epilepsy is a data-driven approach that combines personalized anatomical information with dynamical models of abnormal brain activity to generate spatio-temporal seizure patterns as observed in brain imaging signals. Such a parametric simulator is equipped with a stochastic generative process, which itself provides the basis for inference and prediction of the local and global brain dynamics affected by disorders. However, the calculation of likelihood function at whole-brain scale is often intractable. Thus, likelihood-free inference algorithms are required to efficiently estimate the parameters pertaining to the hypothetical areas in the brain, ideally including the uncertainty. In this detailed study, we present simulation-based inference for the virtual epileptic patient (SBI-VEP) model, which only requires forward simulations, enabling us to amortize posterior inference on parameters from low-dimensional data features representing whole-brain epileptic patterns. We use state-of-the-art deep learning algorithms for conditional density estimation to retrieve the statistical relationships between parameters and observations through a sequence of invertible transformations. This approach enables us to readily predict seizure dynamics from new input data. We show that the SBI-VEP is able to accurately estimate the posterior distribution of parameters linked to the extent of the epileptogenic and propagation zones in the brain from the sparse observations of intracranial EEG signals. The presented Bayesian methodology can deal with non-linear latent dynamics and parameter degeneracy, paving the way for reliable prediction of neurological disorders from neuroimaging modalities, which can be crucial for planning intervention strategies.
Long COVID is associated with extensive in-vivo neuroinflammation on [18F]DPA-714 PET
Authors: Visser Denise , Golla Sandeep S.V. , Verfaillie Sander C.J. , Coomans Emma M. , Rikken Roos M. , van de Giessen Elsmarieke M. , den Hollander Marijke E. , Verveen Anouk , Yaqub Maqsood , Barkhof Frederik , Horn Janneke , Koopman Bart , Schober Patrick , Koch Dook W. , Schuit Robert C. , Windhorst Albert D. , Kassiou Michael , Boellaard Ronald , van Vugt Michele , Knoop Hans , Tolboom Nelleke , van Berckel Bart N.M.
Published: June 2022

A significant number of COVID-19 patients develop ‘long COVID’, a condition defined by long-lasting debilitating, often neurological, symptoms. The pathophysiology of long COVID is unknown. Here we present in-vivo evidence of widespread neuroinflammation in long COVID, using a quantitative assessment, [18F]DPA-714 PET, in two long COVID patients. We reanalyzed historical data from three matched healthy control subjects, for comparison purposes. Both patients with long COVID had widespread increases in [18F]DPA-714 binding throughout the brain. Quantitative measures of binding (BPND values) were increased on average by 121% and 76%, respectively. This implicates profound neuroinflammation in the pathophysiology of long COVID.
Real-world evidence on levodopa dose escalation in patients with Parkinson’s disease treated with istradefylline
Authors: Hattori Nobutaka , Kabata Daijiro , Asada Shinji , Kanda Tomoyuki , Nomura Takanobu , Shintani Ayumi , Mori Akihisa
Published: June 2022

Objective

Istradefylline, a selective adenosine A2A receptor antagonist, is indicated in the US and Japan as adjunctive treatment to levodopa/decarboxylase inhibitors in adults with Parkinson’s disease (PD) experiencing OFF time. This study aimed to observe patterns of dose escalation of levodopa over time in patients initiated on istradefylline.

Methods

Using Japanese electronic health record data, interrupted time series analyses were used to compare levodopa daily dose (LDD, mg/day) gradients in patients before and after initiation of istradefylline. Data were analyzed by period relative to istradefylline initiation (Month 1): pre-istradefylline (Months -72 to 0), early istradefylline (Months 1 to 24), and late istradefylline (Months 25 to 72). Subgroup analyses included LDD before istradefylline initiation (<400, ≥400 to <600, ≥600 mg/day) and treatment with or without monoamine oxidase-B inhibitors (MAO-BIs), catechol-O-methyltransferase inhibitors (COMTIs), or dopamine agonists before istradefylline initiation.

Results

The analysis included 4026 patients; mean (SD) baseline LDD was 419.27 mg (174.19). Patients receiving ≥600 mg/day levodopa or not receiving MAO-BIs or COMTIs demonstrated a significant reduction in LDD increase gradient for pre-istradefylline vs late-phase istradefylline (≥600 mg/day levodopa, -6.259 mg/day each month, p<0.001; no MAO-BIs, -1.819 mg/day each month, p=0.004; no COMTIs, -1.412 mg/day each month, p=0.027).

Conclusions

This real-world analysis of Japanese prescription data indicated that slowing of LDD escalation was observed in patients initiated on istradefylline, particularly in those receiving ≥600 mg/day levodopa, suggesting istradefylline may slow progressive LDD increases. These findings suggest that initiating istradefylline before other levodopa-adjunctive therapies may mitigate LDD increases, potentially reducing occurrence or severity of levodopa-induced complications in long-term istradefylline treatment.
Distinct smell and taste disorder phenotype of post-acute COVID-19 sequelae
Authors: Rass Verena , Tymoszuk Piotr , Sahanic Sabina , Heim Beatrice , Ausserhofer Dietmar , Lindner Anna , Kofler Mario , Mahlknecht Philipp , Boehm Anna , Hüfner Katharina , Pizzini Alex , Sonnweber Thomas , Kurz Katharina , Pfeifer Bernhard , Kiechl Stefan , Peball Marina , Kindl Philipp , Putnina Lauma , Fava Elena , Djamshidian Atbin , Huber Andreas , Wiedermann Christian J. , Sperner-Unterweger Barbara , Wöll Ewald , Beer Ronny , Schiefecker Alois Josef , Bellmann-Weiler Rosa , Bachler Herbert , Tancevski Ivan , Pfausler Bettina , Piccoliori Giuliano , Seppi Klaus , Weiss Günter , Löffler-Ragg Judith , Helbok Raimund
Published: June 2022

Background

Olfactory dysfunction (OD) often accompanies acute coronavirus disease 2019 (COVID-19) and its sequelae. Herein, we investigated OD during COVID-19 recovery in the context of other symptoms, quality of life, physical and mental health.

Methods

Symptom recovery patterns were analyzed in a bi-national, ambulatory COVID-19 survey (n = 906, ≥ 90 days follow-up) and a multi-center observational cross-sectional cohort of ambulatory and hospitalized individuals (n = 108, 360 days follow-up) with multi-dimensional scaling, association rule mining and partitioning around medoids clustering.

Results

Both in the ambulatory collective (72%, n = 655/906) and the cross-sectional ambulatory and hospitalized cohort (41%, n = 44/108) self-reported OD was frequent during acute COVID-19, displayed a slow recovery pace (ambulatory: 28 days, cross-sectional: 90 days median recovery time) and commonly co-occurred with taste disorders. In the ambulatory collective, a predominantly young, female, comorbidity-free group of convalescents with persistent OD and taste disorder (>90 days) was identified. This post-acute smell and taste disorder phenotype was characterized by a low frequency of other leading post-acute symptoms including fatigue, respiratory and neurocognitive complaints. Despite a protracted smell and taste dysfunction, this subset had high ratings of physical performance, mental health, and quality of life.

Conclusion

Our results underline the clinical heterogeneity of post-acute COVID-19 sequelae calling for tailored management strategies. The persistent smell and taste disorder phenotype may represent a distinct COVID-19 recovery pathway characterized by a good recovery of other COVID-19 related symptoms.

Study registration

ClinicalTrials.gov: NCT04661462 (ambulatory collective), NCT04416100 (cross-sectional cohort).
Polygenic Risk Score Improves the Accuracy of a Clinical Risk Score for Coronary Artery Disease
Authors: King Austin , Wu Lang , Deng Hong-Wen , Shen Hui , Wu Chong
Published: June 2022

Background

The value of polygenic risk scores (PRS) towards improving guideline-recommended clinical risk models for coronary artery disease (CAD) prediction is controversial. Here we examine whether an integrated polygenic risk score improves prediction of CAD beyond pooled cohort equations.

Methods

An observation study of 291,305 unrelated White British UK Biobank participants enrolled from 2006 to 2010 was conducted. A case-control sample of 9,499 prevalent CAD cases and an equal number of randomly selected controls was used for tuning and integrating of the polygenic risk scores. A separate cohort of 272,307 individuals (with follow-up to 2020) was used to examine the risk prediction performance of pooled cohort equations, integrated polygenic risk score, and PRS-enhanced pooled cohort equation for incident CAD cases. Performance of each model was analyzed by discrimination and risk reclassification using a 7.5% threshold.

Results

In the cohort of 272,307 individuals (mean age, 56.7 years) used to analyze predictive accuracy, there were 7,036 incident CAD cases over a 12-year follow-up period. Model discrimination was tested for integrated polygenic risk score, pooled cohort equation, and PRS-enhanced pooled cohort equation with reported C-statistics of 0.640 (95% CI, 0.634-0.646), 0.718 (95% CI, 0.713-0.723), and 0.753 (95% CI, 0.748-0.758), respectively. Risk reclassification for the addition of the integrated polygenic risk score to the pooled cohort equation at a 7.5% risk threshold resulted in a net reclassification improvement of 0.117 (95% CI, 0.102 to 0.129) for cases and -0.023 (95% CI, -0.025 to -0.022) for noncases [overall: 0.093 (95% CI, 0.08 to 0.104)]. For incident CAD cases, this represented 14.2% correctly reclassified to the higher-risk category and 2.6% incorrectly reclassified to the lower-risk category.

Conclusions and Relevance

Addition of the integrated polygenic risk score for CAD to the pooled cohort questions improves the predictive accuracy for incident CAD and clinical risk classification in the White British from the UK biobank. These findings suggest that an integrated polygenic risk score may enhance CAD risk prediction and screening in the White British population.
Increase of scabies infestations during the COVID-19 pandemic in Catalonia
Authors: Medina Manuel , Mora Núria , Ramos Francisca , Méndez-Boo Leonardo , Guiriguet Carolina , Hermosilla Eduardo , Fàbregas Mireia , Mas Ariadna , Rodoreda Sara , Coma Ermengol , Fina Francesc
Published: June 2022

During the COVID-19 pandemic, several clinicians in Spain reported an increase in scabies diagnoses. We performed a time-series analysis with data from 2014 to 2022 to quantify this increase. We found an increasing trend during late 2020 and 2021, peaking in March 2022 with an almost 4.5-fold incidence than expected, especially in those aged between 16 and 30 years. Although scabies is more frequent in most socioeconomic deprived areas, the observed rise occurs in all the areas. We recommend increasing surveillance among other countries to detect unexpected increases in scabies outbreaks.
Globalisation and Maternal Health Care Utilisation in sub-Saharan Africa: A Bayesian Multilevel Analysis
Authors: Simona Simona
Published: June 2022

Background

Globalization is considered a major structural determinant of health and health care outcomes across the world. This study examines the influence of globalisation on maternal healthcare utilisation in sub-Saharan Africa.

Methods

Cross-sectional pooled survey data from 34 Demographic and Health Surveys (DHS) with 22559 randomly selected women of reproductive age group with a recent birth were combined with country-level globalisation indices from the KOF Swiss Economic Institute. Bayesian multilevel models were applied on maternal health care utilisation indicators (antenatal care visits, institutional delivery, and postnatal care check-ups) in relation to three dimensions of globalisation indices (economic, social, and political) and selected covariates.

Results

The results from the study demonstrate that the influence of globalisation on maternal healthcare depends on the dimension of globalisation. After controlling for selected individual and community-level factors, social globalisation is significantly associated with all the indicators of maternal healthcare utilisation while economic globalisation is significantly associated with antenatal care and postnatal check-ups for mothers and new-born babies.

Conclusion

More consideration in terms of public policy and further research, should be given to dimensions of globalisation which are more likely to influence maternal healthcare utilisation in sub-Saharan Africa.
Crosshair, semi-automated targeting for electron microscopy with a motorised ultramicrotome
Authors: Meechan Kimberly , Guan Wei , Riedinger Alfons , Stankova Vera , Yoshimura Azumi , Pipitone Rosa , Milberger Arthur , Schaar Helmuth , Romero-Brey Inés , Templin Rachel , Peddie Christopher J , Schieber Nicole L , Jones Martin L , Collinson Lucy , Schwab Yannick
Published: June 2022

Volume electron microscopy (EM) is a time consuming process - often requiring weeks or months of continuous acquisition for large samples. In order to compare the ultrastructure of a number of individuals or conditions, acquisition times must therefore be reduced. For resin-embedded samples, one solution is to selectively target smaller regions of interest by trimming with an ultramicrotome. This is a difficult and labour-intensive process, requiring manual positioning of the diamond knife and sample, and much time and training to master. Here, we have developed a semi-automated workflow for targeting with a modified ultramicrotome. We adapted two recent commercial systems to add motors for each rotational axis (and also each translational axis for one system), allowing precise and automated movement. We also developed a user-friendly software to convert X-ray images of resin-embedded samples into angles and cutting depths for the ultramicrotome. This is provided as an open-source Fiji plugin called Crosshair. This workflow is demonstrated by targeting regions of interest in a series of Platynereis dumerilii samples.
Distinct antibody responses to endemic coronaviruses pre- and post-SARS-CoV-2 infection in Kenyan infants and mothers
Authors: Stoddard Caitlin I. , Sung Kevin , Ojee Ednah , Adhiambo Judith , Begnel Emily R. , Slyker Jennifer , Gantt Soren , Matsen Frederick A. , Kinuthia John , Wamalwa Dalton , Overbaugh Julie , Lehman Dara A.
Published: June 2022

Pre-existing antibodies that bind endemic human coronaviruses (eHCoVs) can cross-react with SARS-CoV-2, the betacoronavirus that causes COVID-19, but whether these responses influence SARS-CoV-2 infection is still under investigation and is particularly understudied in infants. In this study, we measured eHCoV and SARS-CoV-1 IgG antibody titers before and after SARS-CoV-2 seroconversion in a cohort of Kenyan women and their infants. Pre-existing eHCoV antibody binding titers were not consistently associated with SARS-CoV-2 seroconversion in infants or mothers, though we observed a very modest association between pre-existing HCoV-229E antibody levels and lack of SARS-CoV-2 seroconversion in infants. After seroconversion to SARS-CoV-2, antibody binding titers to endemic betacoronaviruses HCoV-OC43 and HCoV-HKU1, and the highly pathogenic betacoronavirus SARS-CoV-1, but not endemic alphacoronaviruses HCoV-229E and HCoV-NL63, increased in mothers. However, eHCoV antibody levels did not increase following SARS-CoV-2 seroconversion in infants, suggesting the increase seen in mothers was not simply due to cross-reactivity to naively generated SARS-CoV-2 antibodies. In contrast, the levels of antibodies that could bind SARS-CoV-1 increased after SARS-CoV-2 seroconversion in both mothers and infants, both of whom are unlikely to have had a prior SARS-CoV-1 infection, supporting prior findings that SARS-CoV-2 responses cross-react with SARS-CoV-1. In summary, we find evidence for increased eHCoV antibody levels following SARS-CoV-2 seroconversion in mothers but not infants, suggesting eHCoV responses can be boosted by SARS-CoV-2 infection when a prior memory response has been established, and that pre-existing cross-reactive antibodies are not strongly associated with SARS-CoV-2 infection risk in mothers or infants.
An Accelerometer Based Heart Monitor to Measure Changes of the Autonomic Nervous System
Authors: Babenko Viktoriya , Dundon Neil M. , Macy Alan , Stump Alexandra , Turbow Macey , Cieslak Matthew , Grafton Scott T.
Published: June 2022

The electrocardiogram (ECG) and impedance cardiography (ICG) are typically combined to estimate electromechanical features such as the pre-ejection period (PEP) and left ventricular ejection time (LVET); indicators of changes in the cardiac specific drive of the autonomic nervous system (ANS). Current methods of ICG are time intensive in subject preparation and the measurements are vulnerable to non-reproducible subject-specific electrode configuration. Furthermore, analysis of impedance waveforms can be time consuming and labeling of key time points can suffer from experimenter bias. Here we present a wearable heart monitor that includes ECG, but replaces the commonly used 8 ICG electrodes with a single accelerometer (ACC) placed at the suprasternal notch. The ACC indirectly measures movement of the arterial pulse wave as blood is ejected into the aorta and great vessels. The resulting ACC waveform is processed into two smooth and readily identified waves, corresponding to the timing of the opening and closing of the aortic valve. We tested the ACC’s utility and reliability for tracking cardiac ANS tone by comparing PEP and LVET measurements obtained simultaneously with conventional ICG and the ACC. Participants were recorded in the sitting and supine position with ECG, ICG, and ACC. While seated, they engaged in a classic physical stress task known to modulate ANS activity. There were obvious and significant associations between ICG and ACC estimates of PEP and LVET derivatives with respect to time. These findings support ACC as a complementary method for tracking ANS that is robust, time efficient, and readily accessible to researchers.