bluuebunny/crossref_metadata_2025 huggingface dataset:
Deploying Bots in Healthcare to Find Revenue Cycle Improvements
Authors: Dunn Rose T.
Published: May 2023

Doing more with less has been a business mantra for decades. Healthcare leaders have implemented flex scheduling and job sharing, streamlined workflows, committed to process improvement techniques such as Lean, hired retirees, gained efficiencies from remote work ... and the list goes on. Each tactic has yielded productivity improvements, yet the need to do more with less continues. Postpandemic challenges include staff recruitment and retention, labor inflation, and dwindling margins, all of which must be addressed while maintaining corporate cultures. The journey with bots described here started in this dynamic environment, and the work has not been single-threaded. The organization featured here—an integrated delivery network—has digital front-door and back-end robotic process automation (RPA) projects underway. The digital front-door initiative supports patient self-registration and automates authorizations and insurance verification processes. The back-end patient financial services RPA project replaces and enhances existing technology. Revenue cycle as a multidepartment function is leadership's poster child for RPA, and the revenue cycle team is tasked to demonstrate the value of the technology. This article covers the initial steps and lessons learned in the process.
How An Established Health System Ventures Forth: Ochsner Invests in the Future
Authors: Quirk Aimee
Published: May 2023

The founding of Ochsner Ventures followed the natural evolution of more than a decade of growth and expansion of Ochsner Health's offerings and capabilities beyond traditional patient care. This growth has enabled the health system to bring critical services to underserved communities across the Gulf South. Ochsner Ventures supports promising companies both in and beyond the region while bringing forward new solutions to healthcare sector challenges and improving health outcomes, access, and equity. In a dynamic healthcare environment amid the persistent effects of the COVID-19 pandemic, Ochsner Health is executing a multiyear strategic plan to reinforce its mission and maintain a position of strength in the region. One aspect of the strategy focuses on the diversification and pursuit of new value by creating new revenue, additional savings, cost reductions, innovations, and amplifying existing assets and capabilities.
For UW Health, Health Plan Ownership Provides Financial Stability
Authors: Kaplan Alan S.
Published: May 2023

For health systems seeking a path forward and upward in a value-based environment, ownership of a health plan can yield many positives, including a chance to drive value-based care, financial margin improvement, and opportunities for rewarding partnerships. However, being both a payer and a provider—a “payvider”—can make extraordinary demands on both the health system and health plan. Developing this hybrid business has been a learning experience for UW Health, an academic medical center that, like others in academic healthcare, was built on a fee-for-service model. Today, UW Health is a majority owner of what has become the state's largest provider-owned health plan. As illustrated here, health plan ownership is not for every system. The burdens are heavy. But for UW Health, it is an important component of both mission and margin.
Programming Levels and Speech Perception in Pediatric Cochlear Implant Recipients With Enlarged Vestibular Aqueduct or GJB2 Mutation
Authors: Jahn Kelly N. , Morse-Fortier Charlotte , Griffin Amanda M. , Faller David , Cohen Michael S. , Kenna Margaret A. , Doney Elizabeth , Arenberg Julie G.
Published: May 2023

Objective

To determine the relationship between hearing loss etiology, cochlear implant (CI) programming levels, and speech perception performance in a large clinical cohort of pediatric CI recipients.

Study Design

Retrospective chart review.

Setting

Tertiary care hospitals.

Patients

A total of 136 pediatric CI recipients (218 ears) were included in this study. All patients had diagnoses of either enlarged vestibular aqueduct (EVA) or GJB2 (Connexin-26) mutation confirmed via radiographic data and/or genetic reports. All patients received audiologic care at either Boston Children's Hospital or Massachusetts Eye and Ear in Boston, MA, between the years 1999 and 2020.

Main Outcome Measures

Electrode impedances and programming levels for each active electrode and speech perception scores were evaluated as a function of etiology (EVA or GJB2 mutation).

Results

Children with EVA had significantly higher impedances and programming levels (thresholds and upper stimulation levels) than the children with GJB2 mutation. Speech perception scores did not differ as a function of etiology in this sample; rather, they were positively correlated with duration of CI experience (time since implantation).

Conclusions

Differences in electrode impedances and CI programming levels suggest that the electrode-neuron interface varies systematically as a function of hearing loss etiology in pediatric CI recipients with EVA and those with GJB2 mutation. Time with the CI was a better predictor of speech perception scores than etiology, suggesting that children can adapt to CI stimulation with experience.
Safety and Effectiveness of Vedolizumab in Elderly Patients with Inflammatory Bowel Disease
Authors: Dahiya Dushyant Singh , Chandan Saurabh , Bapaye Jay , Mohan Babu P. , Ramai Daryl , Kassab Lena L. , Chandan Ojasvini C. , Dulai Parambir S. , Kochhar Gursimran S.
Published: May 2023

Background:

There is limited data on Vedolizumab utilization in elderly patients. Our study aims to assess the effectiveness and safety of Vedolizumab in this subset population.

Materials and Methods:

Databases including Cochrane Central, Embase, Medline (via Ovid), Scopus, and Web of Science were searched in August 2022 to identify studies that assessed Vedolizumab therapy in elderly patients. Pooled proportion and risk ratios (RR) were calculated.

Results:

Total 11 studies with 3546 IBD patients (1314 elderly and 2232 young) were included in the final analysis. Pooled rate of overall and serious infections in the elderly cohort was 8.45% (95% CI=6.27-11.29; I223%) and 2.59% (95% CI=0.78-8.29; I276%), respectively. However, there was no difference in overall infection rates between elderly and young patients. Pooled rate of endoscopic, clinical, and steroid-free remission for elderly IBD patients was 38.45% (95% CI=20.74-59.56; I293%), 37.95% (95% CI=33.08-43.06; I213%), and 38.8% (95% CI=31.6-46.4; I277%), respectively. Elderly patients had lower steroid-free remission rates [RR 0.85, 95% CI=0.74-0.99; I20%, P=0.03]; however, there was no difference in rates of clinical (RR 0.86, 95% CI=0.72-1.03; I20%, P=0.10) or endoscopic remission (RR 1.06, 95% CI=0.83-1.35; I20%, P=0.63) compared with younger patients. Pooled rate of IBD-related surgery and IBD-related hospitalizations was 9.76% (95% CI=5.81-15.92; I278%) and 10.54% (95% CI=8.37-13.2; I20%), respectively for the elderly cohort. There was no statistical difference in IBD-related surgeries between elderly and young IBD patients, RR 1.20 (95% CI=0.79-1.84; I216%), P=0.4.

Conclusions:

Vedolizumab is equally safe and effective for clinical and endoscopic remission in elderly and younger populations.
A Safe and Efficient Technique for Pedicled TRAM Flap Breast Reconstruction
Authors: Semple John L. , Viezel-Mathieu Alex , Alshaqsi Sultan , Armstrong Kathleen
Published: May 2023

Learning Objectives:

After studying this article, the participant should be able to: 1. Understand the indications for a unilateral pedicled transverse rectus abdominis (TRAM) flap-based breast reconstruction. 2. Understand the different types and designs of pedicled TRAM flap used in both immediate and delayed breast reconstruction. 3. Understand the essential landmarks and relevant anatomy of the pedicled TRAM flap. 4. Understand the steps of raising the pedicled TRAM flap, the subcutaneous transfer, and the insetting of the flap on the chest wall. 5. Understand the nature of donor-site management and closure of the defect. 6. Develop a postoperative plan for continuing care and pain management.

This article focuses primarily on the unilateral, ipsilateral pedicled TRAM flap. Although the bilateral pedicled TRAM flap may be a reasonable option in some cases, they have been shown to have a significant impact on abdominal wall strength and integrity. Other types of autogenous flaps using the same lower abdominal tissue, such as a free muscle-sparing TRAM or a deep inferior epigastric flap, can be performed as a bilateral procedure with less impact on the abdominal wall. Breast reconstruction with a pedicled transverse rectus abdominis flap has persisted for decades as a reliable and safe form of autologous breast reconstruction leading to a natural and stable breast shape.
A Nasal Columellar Base Stabilizing Suture Technique
Authors: Baldini Nicolas , Alomani Mohammad , Fonseca Eduardo , Saban Yves
Published: May 2023

When seeking to achieve a more aesthetic and narrower columella, most of the required changes concern the middle and base of the columella. Narrowing and reshaping the columellar base require a sequential approach with a good anatomical knowledge and aesthetics analysis. The columellar base is a three-dimensional structure that must be analyzed following 3 axes: transverse (thickness or width), frontal (height), sagittal (nasolabial angle). Frequently, sutures that aim to close the distance between the medial crura footplates result in modifying the nasolabial angle, as a side effect, due to caudal protrusion of the columellar soft tissue. The question is: how to keep an adequate nasolabial angle? A transverse columellar base stabilizing suture acting on these 3 axes, that enables to maintain the result after the columellar base management, is described in this article.
Human Adipose-Derived Endothelial Progenitor Cells Accelerate Epithelialization of Radiation Ulcer in Nude Mice
Authors: Mori Masanori , Saito Natsumi , Shirado Takako , Wu Yunyan , Asahi Rintaro , Yoshizumi Kayo , Yamamoto Yoshihiro , Zhang Bihang , Yoshimura Kotaro
Published: May 2023

Background:

Co-transplantation of adipose-derived stem cells (ASCs) and endothelial progenitor cells (EPCs) has shown superior angiogenic effects than ASCs alone in recent animal studies. However, EPCs could only be collected from blood vessels or bone marrow. Thus, we have established a method for purifying adipose-derived endothelial progenitor cells (AEPCs). We hypothesized that AEPCs would enhance the therapeutic effect of ASCs on radiation ulcer.

Methods:

Seven-week-old male nude mice (BALB/cAJcl-nu/nu) were irradiated on the dorsal skin (total 40 Gy) and twelve weeks later 6 mm diameter wounds were created. The mice were then treated with subcutaneous injection of human ASCs (1×10 5, n = 4), human AEPCs (2×10 5 or 5×10 5, n = 5), combinations of those (ASCs 1×10 5 + AEPCs 2×10 5 (n = 4) or 5×10 5 (n = 5)), or only vehicle (n = 7). Non-irradiated group was also prepared as a control (n = 6). The days required for macroscopic epithelialization was compared and immunostaining for human-derived cells and vascular endothelial cells was performed at Day 28.

Results:

AEPC-ASC combination-treated groups healed faster than ASC-treated group (14 ± 0 vs 17 ± 2 days, p < 0.01). Engraftment of the injected cells could not be confirmed. Only the non-irradiated mice had significantly higher vascular density (0.988 ± 0.183 vs 0.474 ± 0.092 ×10 -5µm -2, p = 0.02).

Conclusions:

The results suggested therapeutic potentials of AEPCs and an enhanced effect of combination with ASCs. This study is a xenogenic transplantation model and further validation in an autologous transplantation model is needed.

Clinical Relevance Statement:

Human AEPCs and its combination with ASCs accelerated epithelialization of radiation ulcer in nude mice. It was also suggested that administration of humoral factors secreted from AEPCs, e.g. treatment with culture conditioned media, could be used for the same purpose.
The ever-growing case for clozapine in the treatment of schizophrenia: an obligation for psychiatrists and psychiatry
Authors: Bittner Robert A. , Reif Andreas , Qubad Mishal
Published: May 2023

Purpose of review

Clozapine remains the gold standard for treatment-resistant schizophrenia (TRS). Although the evidence base for its wide-ranging, unique efficacy continues to expand, clozapine remains alarmingly underutilized in industrialized countries. Analyzing the causes and consequences of this problem is crucial for substantially improving the quality of care for TRS patients.

Recent findings

Clozapine is the most effective antipsychotic for reducing all-cause mortality in TRS. In most cases, treatment resistance emerges during the first psychotic episode. Delaying clozapine treatment has a negative impact on long-term outcome. Patients’ experience with clozapine treatment is largely positive despite a comparatively high rate of side effects. Patients prefer clozapine, while psychiatrists regard it as a burden due to concerns regarding safety and side effect management. Shared decision-making (SDM), which increases the likelihood of a clozapine recommendation, is not routinely used, possibly due to stigmatization of TRS patients.

The mortality-reducing effects of clozapine alone warrant its regular use. Therefore, psychiatrists must not exclude patients from the decision regarding a clozapine trial by not even offering it. Rather, they have a clear obligation to align their actions more closely with the existing evidence and patients’ needs and to facilitate the timely initiation of clozapine.
The final frontier: ecological and evolutionary dynamics of a global parasite invasion
Authors: Chapman Nadine C. , Colin Théotime , Cook James , da Silva Carmen R. B. , Gloag Ros , Hogendoorn Katja , Howard Scarlett R. , Remnant Emily J. , Roberts John M. K. , Tierney Simon M. , Wilson Rachele S. , Mikheyev Alexander S.
Published: May 2023

Studying rapid biological changes accompanying the introduction of alien organisms into native ecosystems can provide insights into fundamental ecological and evolutionary theory. While powerful, this quasi-experimental approach is difficult to implement because the timing of invasions and their consequences are hard to predict, meaning that baseline pre-invasion data are often missing. Exceptionally, the eventual arrival of
Varroa destructor
(hereafter Varroa) in Australia has been predicted for decades. Varroa is a major driver of honeybee declines worldwide, particularly as vectors of diverse RNA viruses. The detection of Varroa in 2022 at over a hundred sites poses a risk of further spread across the continent. At the same time, careful study of Varroa's spread, if it does become established, can provide a wealth of information that can fill knowledge gaps about its effects worldwide. This includes how Varroa affects honeybee populations and pollination. Even more generally, Varroa invasion can serve as a model for evolution, virology and ecological interactions between the parasite, the host and other organisms.
Geographical modelling of language decline
Authors: Brown Douglas , Wrathmall Steven
Published: May 2023

Competition between languages affects the lives of people all over the globe, and a huge number of languages are at risk of extinction. In this work, statistical physics is applied to modelling the decline of one language in competition with another. A model from the literature is used and adapted to model the interactions among speakers in a population distribution over time, and is applied to historical data for Cornish and Welsh. Visual, geographical models show the simulated decline of the real languages studied, and a number of qualitative and quantitative features from the historical data are captured by the model. The applicability of the model to further real situations is discussed, as well as adaptations that would be needed to better take account of migration and population dynamics.
Preparation of hybrid particles of Ag nanoparticles and eggshell calcium carbonate and their antimicrobial efficiency against beef-extracted bacteria
Authors: Zin Moe Ei Ei , Moolkaew Pornpimol , Junyusen Tiraporn , Sutapun Wimonlak
Published: May 2023

In this study, hybrid particles of AgNPs-loaded eggshell calcium carbonate (AgNPs/eCaCO
3
) were prepared by co-precipitating the eggshell in the presence of freshly prepared AgNPs with a particle size of 10–30 nm. The hybrid particles were comparatively precipitated at 25°C and 35°C using poly (sodium 4-styrenesulfonate) as a polyelectrolyte. The AgNPs/eCaCO
3
particles prepared at 25°C had a spherical morphology with a mean diameter of 3.56 µm, and Brunauer–Emmett–Teller (BET) surface area of 85.08 m
2
g
−1
. On the other hand, the particles prepared at 35°C had a broader size distribution with a mean diameter of 3.19 µm, and a BET surface area of 79.25 m
2
g
−1
. AgNPs-loaded commercial calcium carbonate particles (AgNPs/CaCO
3
) comparatively prepared at 35°C were perfectly spherical with a mean diameter of 5.61 µm. At preparing temperature of 25°C, the hybrid particles contain AgNPs of 0.78 wt% for AgNPs/eCaCO
3
and 3.20 wt% for AgNPs/CaCO
3
. The AgNPs/eCaCO
3
and AgNPs/CaCO
3
particles exhibited the same efficiency against bacteria extracted from beef with an average inhibition zone diameter of 7–10 mm according to the modified Kirby–Bauer disc diffusion assay depending on their concentration and beef source. Freshly prepared silver colloids showed comparatively poorer antimicrobial efficiency.
The psychological basis of reductions in food desire during satiety
Authors: Stevenson Richard J. , Francis Heather M. , Wylie Fiona , Hughes Alannah
Published: May 2023

Satiety—the reduced desire to eat, drink or have sex in their respective aftermath—is particularly important for feeding, where it assists energy balance. During satiety, the anticipated pleasure of eating is far less than the actual pleasure of eating. Here we examine two accounts of this effect: (i) satiety signals inhibit retrieval of pleasant food memories that form desirable images, allowing unpleasant memories into mind; (ii) feelings of fullness reflect what eating would be like now, negating the need for imagery. To test these accounts, participants undertook two tasks pre- and post-lunch: (i) judging desire for palatable foods either with or without imagery impairing manipulations; (ii) explicitly recollecting food memories. Impairing imagery reduced desire equally, when hungry and sated. Food-memory recollections became more negative/less positive when sated, with this correlating with changes in desire. These findings support the first account and suggest imagery is used when hungry and when sated to simulate eating, and that the content of these memory-based simulations changes with state. The nature of this process and its implications for satiety more generally are discussed.
Temporal avoidance as a means of reducing competition between sympatric species
Authors: Maziarz Marta , Broughton Richard K. , Beck Kristina B. , Robinson Robert A. , Sheldon Ben C.
Published: May 2023

Human activity has modified the availability of natural resources and the abundance of species that rely on them, potentially changing interspecific competition dynamics. Here, we use large-scale automated data collection to quantify spatio-temporal competition among species with contrasting population trends. We focus on the spatial and temporal foraging behaviour of subordinate marsh titsPoecile palustrisamong groups of socially and numerically dominant blue titsCyanistes caeruleusand great titsParus major. The three species exploit similar food resources in mixed groups during autumn–winter. Using 421 077 winter recordings of individually marked birds at 65 automated feeding stations in Wytham Woods (Oxfordshire, UK), we found that marsh tits were less likely to join larger groups of heterospecifics, and they accessed food less frequently in larger groups than in smaller ones. Marsh tit numbers within groups declined throughout the diurnal and winter periods, while the number of blue and great tits increased. However, sites that attracted larger groups of these heterospecifics also attracted more marsh tits. The results suggest that subordinate species exhibit temporal avoidance of socially and numerically dominant heterospecifics, but have limited ability for spatial avoidance, indicating that behavioural plasticity enables only a partial reduction of interspecific competition.
Photonic ternary quantum random number generators
Authors: Trejo José Manuel Agüero , Calude Cristian S.
Published: May 2023

We construct a class of three-dimensional photonic quantum random number generators (QRNGs) and prove that each of them generates maximally unpredictable digits via measurements that are robust to errors. This shows that every sequence generated is strongly incomputable; hence its quality is provably better than that of every pseudo-random sequence. These results suggest that incomputability in physics is real and practically applicable. Finally, we present photonic implementations of three-dimensional QRNGs and discuss device independence.
Non-Abelian mechanics of elastic waves in Kagome metamaterials with internal microstructures
Authors: Yang Zi-Jiang , Wang Yi-Ze
Published: May 2023

In this work, the duality of mechanical Kagome lattices with internal microstructures is studied and its non-Abelian characteristics of wave packet evolution are discussed. Based on Bloch's theorem, the dynamical and duality matrices are obtained during elastic wave propagation. By regulating the twisting angles of the Kagome lattices and internal microstructures, global twofold degeneracy and unequal Berry phase can be obtained. A fourfold degeneracy appears at
Γ
point when the mechanical metamaterial is subjected to a special twisting state. Numerical calculations of non-Abelian mechanics and duality are performed, in which band structures with special twisting angles are the same. In addition, the solution of the Wilson operator is derived by the elastic wave equation and gauge transformation, which has non-exchangeable product and leads to the non-Abelian Berry curvature. If the time-reversal symmetry is broken, non-commutative elastic wave responses can be generated. The generalized polarization and wave propagation become different when the acting sequences of external forces are exchanged.
Post-injection aseismic slip as a mechanism for the delayed triggering of seismicity
Authors: Sáez Alexis , Lecampion Brice
Published: May 2023

Injection-induced aseismic slip plays an important role in a broad range of human-made and natural systems, from the exploitation of geo-resources to the understanding of earthquakes. Recent studies have shed light on how aseismic slip propagates in response to continuous fluid injections. Yet much less is known about the response of faults after the injection of fluids has stopped. In this work, we investigate via a hydro-mechanical model the propagation and ultimate arrest of aseismic slip during the so-called post-injection stage. We show that after shut-in, fault slip propagates in pulse-like mode. The conditions that control the propagation as a pulse and notably when and where the ruptures arrest are fully established. In particular, critically stressed faults can host rupture pulses that propagate for several orders of magnitude the injection duration and reach up to nearly double the size of the ruptures at the moment of shut-in. We consequently argue that the persistent stressing of increasingly larger rock volumes caused by post-injection aseismic slip is a plausible mechanism for the triggering of post-injection seismicity—a critical issue in the geo-energy industry. Our physical model shows quantitative agreement with field observations of documented cases of post-injection induced seismicity.
Kinematics and dynamics of disclination lines in three-dimensional nematics
Authors: Schimming Cody D. , Viñals Jorge
Published: May 2023

An exact kinematic law for the motion of disclination lines in nematic liquid crystals as a function of the tensor order parameterQis derived. Unlike other order parameter fields that become singular at their respective defect cores, the tensor order parameter remains regular. Following earlier experimental and theoretical work, the disclination core is defined to be the line where the uniaxial and biaxial order parameters are equal, or equivalently, where the two largest eigenvalues ofQcross. This allows an exact expression relating the velocity of the line to spatial and temporal derivatives ofQon the line, to be specified by a dynamical model for the evolution of the nematic. By introducing a linear core approximation forQ, analytical results are given for several prototypical configurations, including line interactions and motion, loop annihilation, and the response to external fields and shear flows. Behaviour that follows from topological constraints or defect geometry is highlighted. The analytic results are shown to be in agreement with three-dimensional numerical calculations based on a singular Maier–Saupe free energy that allows for anisotropic elasticity.
Hypothalamus volumes in adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Impact of self-reported fatigue and illness duration
Authors: Byrne Hollie , Josev Elisha K , Knight Sarah J , Scheinberg Adam , Rowe Katherine , Lubitz Lionel , Seal Marc L
Published: May 2023

Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex illness of unknown aetiology. Emerging theories suggest ME/CFS may reflect a progressive, aberrant state of homeostasis caused by disturbances within the hypothalamus, yet few studies have investigated this using magnetic resonance imaging in adolescents with ME/CFS. We conducted a volumetric analysis to investigate whether whole and regional hypothalamus volumes in adolescents with ME/CFS differed compared to healthy controls, and whether these volumes were associated with fatigue severity and illness duration. 48 adolescents (25 ME/CFS, 23 controls) were recruited. Lateralised whole and regional hypothalamus volumes, including the anterior–superior, superior tubular, posterior, anterior-inferior and inferior tubular subregions, were calculated from T1-weighted images. When controlling for age, sex and intracranial volume, Bayesian linear regression revealed no evidence for differences in hypothalamus volumes between groups. However, in the ME/CFS group, a negative linear relationship between right anterior-superior volumes and fatigue severity was identified, which was absent in controls. In addition, Bayesian ordinal regression revealed a likely-positive association between illness duration and right superior tubular volumes in the ME/CFS group. While these findings suggest overall comparability in regional and whole hypothalamus volumes between adolescents with ME/CFS and controls, preliminary evidence was identified to suggest greater fatigue and longer illness duration were associated with greater right anterior-superior and superior-tubular volumes, respectively. These regions contain the anterior and superior divisions of the paraventricular nucleus, involved in the neuroendocrine response to stress, suggesting involvement in ME/CFS pathophysiology. However, replication in a larger, longitudinal cohort is required.
Disentangling visual exploration differences in cognitive impairment
Authors: Jiang Zifan , Seyedi Salman , Vickers Kayci L. , Manzanares Cecelia M. , Lah James J. , Levey Allan I. , Clifford Gari D.
Published: May 2023

Objective

Compared to individuals without cognitive impairment (CI), those with CI exhibit differences in both basic oculomotor functions and complex viewing behaviors. However, the characteristics of the differences and how those differences relate to various cognitive functions have not been widely explored. In this work we aimed to quantify those differences and assess general cognitive impairment and specific cognitive functions.

Methods

A validated passive viewing memory test with eyetracking was administered to 348 healthy controls and CI individuals. Spatial, temporal, semantic, and other composite features were extracted from the estimated eye-gaze locations on the corresponding pictures displayed during the test. These features were then used to characterize viewing patterns, classify cognitive impairment, and estimate scores in various neuropsychological tests using machine learning.

Results

Statistically significant differences in spatial, spatiotemporal, and semantic features were found between healthy controls and individuals with CI. CI group spent more time gazing at the center of the image, looked at more regions of interest (ROI), transitioned less often between ROI yet in a more unpredictable manner, and had different semantic preferences. A combination of these features achieved an area under the receiver-operator curve of 0.78 in differentiating CI individuals from controls. Statistically significant correlations were identified between actual and estimated MoCA scores and other neuropsychological tests.

Conclusion

Evaluating visual exploration behaviors provided quantitative and systematic evidence of differences in CI individuals, leading to an improved approach for passive cognitive impairment screening.

Significance

The proposed passive, accessible, and scalable approach could help with earlier detection and a better understanding of cognitive impairment.
BRAVEHEART: Open-source software for automated electrocardiographic and vectorcardiographic analysis
Authors: Stabenau Hans Friedrich , Waks Jonathan W.
Published: May 2023

Background and Objectives

Electrocardiographic (ECG) and vectorcardiographic (VCG) analyses are used to diagnose current cardiovascular disease and for risk stratification for future adverse cardiovascular events. With increasing use of digital ECGs, research into novel ECG/VCG parameters has increased, but widespread computer-based ECG/VCG analysis is limited because there are no currently available, open-source, and easily customizable software packages designed for automated and reproducible analysis.

Methods and Results

We present BRAVEHEART, an open-source, modular, customizable, and easy to use software package implemented in the MATLAB programming language, for scientific analysis of standard 12-lead ECGs acquired in a digital format. BRAVEHEART accepts a wide variety of digital ECG formats and provides complete and automatic ECG/VCG processing with signal filtering to remove high- and low-frequency artifact, non-dominant beat identification and removal, accurate fiducial point annotation, VCG construction, median beat construction, customizable measurements on median beats, and output of measurements and results in numeric and graphical formats.

Conclusions

The BRAVEHEART software package provides easily customizable scientific analysis of ECGs and VCGs. We hope that making BRAVEHART available will allow other researchers to further the field of EVG/VCG analysis without having to spend significant time and resources developing their own ECG/VCG analysis software and will improve the reproducibility of future studies. Source code, compiled executables, and a detailed user guide can be found athttp://github.com/BIVectors/BRAVEHEART. The source code is distributed under the GNU General Public License version 3.
Factors associated with unfavorable outcome after anterior circulation stroke despite successful reperfusion and early neurological improvement
Authors: Jesser Jessica , Nagel Simon , Bendszus Martin , Schönenberger Silvia , Ringleb Peter A. , Herweh Christian , Möhlenbruch Markus A. , Vey Johannes A. , Nguyen Thanh N. , Weyland Charlotte S.
Published: May 2023

Background and Purpose

Successful reperfusion during endovascular therapy (EVT) usually leads to early neurological improvement (ENI), yet some patients do not achieve good long-term outcome. The aim of this study was to investigate factors associated with unfavorable clinical outcome (UCO) despite ENI.

Methods

This was a retrospective single-center analysis of consecutive patients treated for anterior circulation large vessel occlusion who achieved successful reperfusion and ENI (at least 20% lower follow-up NIHSS compared to NIHSS on admission) between 01/2014 and 04/2019. The primary endpoint was unfavorable outcome (90-day mRS > 2 or mRS > pre-stroke mRS). Patients with favorable clinical outcome (FCO) and UCO despite ENI were compared in univariable regression analysis.

Results

Successful EVT (mTICI 2c-3) and ENI occurred in 396/549 (72.1 %) patients and unfavorable outcome despite ENI in 168/396 (42.2 %) patients. Factors associated with UCO were pre-stroke mRS (Odds ratio (OR) 3.13 95% confidence interval (CI) 2.53–3.96, p < 0.001), age (OR 1.09 CI 1.07-1.12, p < 0.001), baseline NIHSs (OR 1.09 CI 1.06-1.13, p < 0.001), female sex (OR 1.92 CI 1.28-2.89, p = 0.002), hypertension (OR 2.32 CI 1.37-4.03, p = 0.002), smoking (OR 0.48 CI 0.25-0.87, p = 0.019), history of previous stroke (OR 2.7 CI 1.61-4.59, p < 0.001), atrial fibrillation (OR 1.73 CI 1.16-2.6, p = 0.007), neutrophil-lymphocyte ratio (OR 1.05 CI 1.01 – 1.09, p = 0.014), as well as ASPECTS after EVT (OR 0.77 CI 0.68-0.86, p < 0.001), TAN score (OR 0.60 CI 0.46-0.78, p < 0.001) and Swieten score (OR 2.55 CI 1.87-3.54, p < 0.001). Several ASPECTS regions were associated with UCO despite ENI (insula, M1-M3 and M5).

Conclusions

Relevant factors associated with UCO despite successful EVT and ENI were patient age, sex, pre-stroke mRS, hypertension, history of smoking, previous stroke, atrial fibrillation, neutrophil-lymphocyte ratio, TAN and Swieten Score as well as ASPECTS after EVT. The involvement of certain brain regions by ASPECTS segments were associated with UCO despite ENI after EVT.
Psychiatric hospital admissions and linkages to ambulatory services in the Western Cape Province of South Africa (2015-2022): trends, risk factors and possible opportunities for intervention
Authors: Hussey Hannah , Mountford Timothy , Heekes Alexa , Dean Carol , Roelofse Marinda , Hendricks Lynne , Cossie Qhama , Koen Liezel , Cesar Warren , Lomas Vanessa , Pienaar David , Perez Giovanni , Boulle Andrew , Sorsdahl Katherine , Mahomed Hassan
Published: May 2023

Background

Psychiatric hospital admissions in the Western Cape are increasing, driven by poverty and substance use.

Aim

To assess the trend of psychiatric admissions from 2015-2022 and factors associated with repeat psychiatric admissions and linkage to ambulatory services post-discharge.

Setting

Public hospitals in the Western Cape, South Africa

Methods

Using electronic data from the Provincial Health Data Centre, a consolidated routine service database, all psychiatric hospital admissions in the Western Cape were analyzed, stratified by hospital level. Mixed effects logistic regression was used to determine factors associated with successful linkage to ambulatory services within 30 days following hospital discharge, and repeat psychiatric admission within 30 and 90 days.

Results

Psychiatric hospital admissions, particularly at the district/acute level, were increasing prior to 2020 and an increasing proportion were substance related. 40% of admissions at the district level had not been seen at a primary health care facility in the year prior to admission. Males and those with substance use disorders were less likely to be successfully linked to outpatient services post-discharge. Successful linkage was most protective against readmission within 90 days with an adjusted odds ratio of 0.76 (95%CI 0.73-0.79) and 0.45 (95%CI 0.42-0.49) at district/acute and specialized hospitals respectively.

Conclusion

Improving linkage to ambulatory services for mental health patients post-discharge is likely to avert hospital readmissions.

Contribution

This research highlights how often mental health patients requiring admissions are not seen at the primary health care level and quantifies the risk for readmission of not following up psychiatric admissions post-discharge.
Large tandem duplications in cancer result from transcription and DNA replication collisions
Authors: Yang Yang , Badura Michelle L. , O’Leary Patrick C. , Delavan Henry M. , Robinson Troy M. , Egusa Emily A. , Zhong Xiaoming , Swinderman Jason T. , Li Haolong , Zhang Meng , Kim Minkyu , Ashworth Alan , Feng Felix Y. , Chou Jonathan , Yang Lixing
Published: May 2023

Despite the abundance of somatic structural variations (SVs) in cancer, the underlying molecular mechanisms of their formation remain unclear. Here, we use 6,193 whole-genome sequenced tumors to study the contributions of transcription and DNA replication collisions to genome instability. After deconvoluting robust SV signatures in three independent pan-cancer cohorts, we detect transcription-dependent replicated-strand bias, the expected footprint of transcription-replication collision (TRC), in large tandem duplications (TDs). Large TDs are abundant in female-enriched, upper gastrointestinal tract and prostate cancers. They are associated with poor patient survival and mutations inTP53,CDK12, andSPOP. Upon inactivating CDK12, cells display significantly more TRCs, R-loops, and large TDs. Inhibition of G2/M checkpoint proteins, such as WEE1, CHK1, and ATR, selectively inhibits the growth of cells deficient in CDK12. Our data suggest that large TDs in cancer form due to TRCs, and their presence can be used as a biomarker for prognosis and treatment.
Functional connectivity of cognition-related brain networks in adults with fetal alcohol syndrome
Authors: Sundermann Benedikt , Feldmann Reinhold , Mathys Christian , Rau Johanna M. H. , Garde Stefan , Braje Anna , Weglage Josef , Pfleiderer Bettina
Published: May 2023

Background

Fetal Alcohol Syndrome (FAS) can result in substantial cognitive dysfunction. Many of the cognitive functions affected are subserved by few functional brain networks. Functional connectivity (FC) in these networks can be assessed with resting state functional MRI (rs-fMRI). Alterations of FC have been reported in children and adolescents prenatally exposed to alcohol. However, previous reports varied substantially regarding which exact cognitive networks were affected, their interactions, and the directionalities of FC alterations. Despite persisting deficits, no previous studies have examined FC in older individuals. Purpose of this rs-fMRI study was to assess FC within and between cognition-related networks in young adults with FAS.

Methods

Cross-sectional study in patients with FAS (n = 39, age: 20.9 ± 3.4 years) and controls without prenatal alcohol exposure (n = 44, age: 22.2 ± 3.4 years). FC was calculated as correlation between cortical regions in ten cognition-related sub-networks. Subsequent modelling of overall FC was based on two-tailed t-tests comparing FC between FAS and controls. Results were subjected to a hierarchical statistical testing approach, first determining whether there is any alteration of FC in FAS (compared with controls) in the full cognitive connectome, subsequently resolving these findings to the level of either FC within each network or between networks, and finally to individual connections. The overall and network-level tests are based on the Higher Criticism (HC) approach for the detection of rare and week effects in high dimensional data. In an additional exploratory time- resolved FC analysis, potential group differences of dynamic FC states were assessed.

Results

Comparing FAS subjects with controls, we observed altered FC of cognition-related brain regions globally, within 7 out of 10 networks, and between networks employing the HC statistic. This was most obvious in the dorsal attention A sub-network, followed by the salience / ventral attention A subnetwork. Findings also spanned subcomponents of the fronto-parietal control and default mode networks. None of the single FC alterations within these networks yielded statistical significance in the final high-resolution analysis. The exploratory time-resolved FC analysis did not show significant group differences in the temporal behavior of FC states.

Conclusions

FC in cognition-related brain networks was altered in adults with FAS. Effects were widely distributed across these networks, potentially reflecting the diversity of cognitive deficits in these individuals. Findings were pronounced in attention-related networks in line with attentional deficits previously reported. An additional exploratory time-resolved FC analysis did not reveal altered dynamic FC patterns.
Development of molecular subtype specific prognostic marker signature in immune response associated colon cancer through fuzzy based transcriptomic approach
Authors: Koçhan Necla , Dayanç Barış Emre
Published: May 2023

Objective

The molecular heterogeneity of colon cancer makes the prediction of disease prognosis challenging. In order to resolve this heterogeneity, molecular tumor subtyping present solutions. These approaches are expected to contribute to clinical decision-making. In this study, we aimed to identify Consensus Molecular Subtype (CMS) specific prognostic genes of colon cancer, focusing on anti-tumor immune-response associated CMS1, through a fuzzy-based machine learning approach.

Materials and Methods

We applied Fuzzy C-Means (FCM) clustering to stratify patients into two groups and identified genes that predict significant disease-specific survival difference between groups. We then performed Cox regression analyses to identify the most significant genes associated with disease-specific survival. A subtype-specific risk score and a final risk score formulae were constructed and used to calculate risk scores to stratify patients into low and high-risk groups within each CMS (1 to 4) or independent of CMS respectively.

Results

We identified CMS-specific genes and an overall 11-gene signature for prognostic risk prediction based on the disease-specific survival of colon cancer patients. The patients in both discovery and test cohorts were stratified into high and low-risk groups using subtype risk scores. The disease-specific survival of these risk groups within each CMS, except CMS3, was significantly different for both discovery and test cohorts.

Discussion and Conclusions

We have identified novel prognostic genes with potential immune regulatory roles within the immune-response associated CMS1. The low number of patients in the CMS3 cohort prevented subtype-specific prognostic gene validation. Tumor stage grouping of the validation cohort suggested the best prediction of prognosis in tumor stage III patients. In conclusion, newly identified eleven genes can efficiently predict the prognostic risk of colon cancer patients and classify patients into corresponding risk groups.

Graphical Abstract
Diagnostic Yield of Exome Sequencing in a Diverse Pediatric and Prenatal Population is not Associated with Genetic Ancestry
Authors: Mavura Yusuph , Sahin-Hodoglugil Nuriye , Hodoglugil Ugur , Kvale Mark , Martin Pierre-Marie , Van Ziffle Jessica , Devine W. Patrick , Ackerman Sara L. , Koenig Barbara A , Kwok Pui-Yan , Norton Mary E. , Slavotinek Anne , Risch Neil
Published: May 2023

Purpose

It has been hypothesized that diagnostic yield (DY) from Exome Sequencing (ES) may be lower among patients with non-European ancestries than those with European ancestry. We examined the association of DY with estimated continental genetic ancestry in a racially/ethnically diverse pediatric and prenatal clinical cohort.

Methods

Cases (N=845) with suspected genetic disorders underwent ES for diagnosis. Continental genetic ancestry proportions were estimated from the ES data. We compared the distribution of genetic ancestries in positive, negative, and inconclusive cases by Kolmogorov Smirnov tests and linear associations of ancestry with DY by Cochran-Armitage trend tests.

Results

We observed no reduction in overall DY associated with any continental genetic ancestry (Africa, America, East Asia, Europe, Middle East, South Asia). However, we observed a relative increase in proportion of autosomal recessive homozygous inheritance versus other inheritance patterns associated with Middle Eastern and South Asian ancestry, due to consanguinity.

Conclusions

In this empirical study of ES for undiagnosed pediatric and prenatal genetic conditions, genetic ancestry was not associated with the likelihood of a positive diagnosis, supporting the ethical and equitable use of ES in diagnosis of previously undiagnosed but potentially Mendelian disorders across all ancestral populations.
Fundamental equations linking methylation dynamics to maximum lifespan in mammals
Authors: Horvath Steve , Zhang Joshua , Haghani Amin , Lu Ake T. , Fei Zhe
Published: May 2023

We establish the mathematical foundation that links the rate of change in any molecular biomarker to species lifespan. Specifically, we propose a robust approach that identifies the strong inverse relationship for certain biomarkers using two comprehensive methylation datasets. After examining 54 chromatin states, we found the rates of change of CpG sites in bivalent chromatin states are negatively associated to the lifespans of 90 dog breeds in the first dataset, and the discoveries are further strengthened with 125 mammalian species in the second dataset. Our research leads to three key findings: First, a reciprocal relationship exists between the average rate of methylation change (AROCM) in bivalent promoter regions and maximum lifespan: AROCM ∝ 1/MaxLifespan. Second, the correlation between age and average methylation bears no relation to maximum lifespan, Cor(Methly,Age) ⊥ MaxLifespan. Third, the rate of methylation change in young animals is related to that in old animals: Young animals’ AROCM ∝ Old AROCM. These findings hinge on the chromatin context, as different results emerge when defining AROCM using different chromatin states. Our analytical framework is versatile and readily extendable to a broad range of other molecular assessments. Overall, our study demonstrates that epigenetic aging rates in specific chromatin states exhibit an inverse relationship with maximum lifespan in mammals.
P53 and BCL-2 family proteins PUMA and NOXA define competitive fitness in Pluripotent Cells
Authors: Valverde-Lopez Jose A. , Li-Bao Lin , Díaz-Díaz Covadonga , Sierra Rocío , Santos Elisa , Giovinazzo Giovanna , Torres Miguel
Published: May 2023

Cell Competition is a process by which neighboring cells compare their fitness. As a result, viable but suboptimal cells are selectively eliminated in the presence of fitter cells. In the early mammalian embryo, epiblast pluripotent cells undergo extensive Cell Competition, which prevents suboptimal cells from contributing to the newly forming organism. While competitive ability is regulated by MYC in the epiblast, the mechanisms that contribute to competitive fitness in this context are largely unknown. Here, we report that P53 and its pro-apoptotic targets PUMA and NOXA regulate apoptosis susceptibility and competitive fitness in pluripotent cells. PUMA is widely expressed specifically in pluripotent cellsin vitroandin vivo. We show that the p53-PUMA/NOXA pathway regulates mitochondrial membrane potential and oxidative status. We found that P53 regulates MYC levels in pluripotent cells, which connects these two Cell competition pathways, however, MYC and PUMA/NOXA levels are independently regulated by P53. We propose a model that integrates a bifurcated P53 pathway regulating both MYC and PUMA/NOXA levels and determines competitive fitness through regulation of mitochondrial activity.