bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring new frontiers in prostate cancer research: Report from the 2022 Coffey−Holden prostate cancer academy meeting
Authors: Miyahira Andrea K. , Hawley Jessica E. , Adelaiye‐Ogala Remi , Calais Jeremie , Nappi Lucia , Parikh Ravi , Seibert Tyler M. , Wasmuth Elizabeth V. , Wei Xiao X. , Pienta Kenneth J. , Soule Howard R.
Published: November 2022

Introduction

The 2022 Coffey−Holden Prostate Cancer Academy (CHPCA) Meeting, “Exploring New Frontiers in Prostate Cancer Research,” was held from June 23 to 26, 2022, at the University of California, Los Angeles, Luskin Conference Center, in Los Angeles, CA.

Methods

The CHPCA Meeting is an annual discussion‐oriented scientific conference organized by the Prostate Cancer Foundation, that focuses on emerging and next‐step topics deemed critical for making the next major advances in prostate cancer research and clinical care. The 2022 CHPCA Meeting included 35 talks over 10 sessions and was attended by 73 academic investigators.

Results

Major topic areas discussed at the meeting included: prostate cancer diversity and disparities, the impact of social determinants on research and patient outcomes, leveraging real‐world and retrospective data, development of artificial intelligence biomarkers, androgen receptor (AR) signaling biology and new strategies for targeting AR, features of homologous recombination deficient prostate cancer, and future directions in immunotherapy and nuclear theranostics.

Discussion

This article summarizes the scientific presentations from the 2022 CHPCA Meeting, with the goal that dissemination of this knowledge will contribute to furthering global prostate cancer research efforts.
Molecular dynamics study reveals key disruptors of MEIG1–PACRG interaction
Authors: Hasse Timothy , Zhang Zhibing , Huang Yu‐ming M.
Published: November 2022

Interactions between the meiosis‐expressed gene 1 (MEIG1) and Parkin co‐regulated gene (PACRG) protein are critical in the formation of mature sperm cells. Targeting either MEIG1 or PACRG protein could be a contraceptive strategy. The W50A and Y68A mutations on MEIG1 are known to interrupt the MEIG1–PACRG interactions resulting in defective sperm cells. However, the details about how the mutants disrupt the protein–protein binding are not clear. In this study, we reveal insights on MEIG1 and PACRG protein dynamics by applying Gaussian‐accelerated molecular dynamics (GaMD) simulations and post‐GaMD analysis. Our results show that the mutations destabilize the protein–protein interfacial interaction. The effect of the Y68A mutation is more significant than W50A as Y68 forms stronger polar interactions with PACRG. Because both human and mouse models demonstrate similar dynamic properties, the findings from mouse proteins can be applied to the human system. Moreover, we report a potential ligand binding pocket on the MEIG1 and PACRG interaction surface that could be a target for future drug design to inhibit the MEIG1–PACRG interaction. PACRG shows more qualified pockets along the protein–protein interface, implying that it is a better target than MEIG1. Our work provides a fundamental understanding of MEIG1 and PACRG protein dynamics, paving the way for drug discovery in male‐based contraception.
Discrete gain scheduling control approach to elliptical orbit rendezvous system with actuator saturation
Authors: Gao Xiangyu , He Dongyan , Teo Kok Lay , Wang Jianqiao , Yang Hongfu
Published: November 2022

This paper studies the discrete gain scheduling control design problem of elliptical orbit spacecraft rendezvous system with actuator saturation. Due to the presence of actuator saturation, the dynamic performance of the spacecraft rendezvous system degrades significantly. In order to improve the dynamic performance of the system, a discrete gain scheduling control approach is adopted to construct a group of time‐invariant ellipsoidal invariant sets, which can be used to determine the switching points of the discrete gain scheduling control. By choosing some discrete parameter values, the discrete gain scheduling control is obtained from a solution of a periodic Riccati matrix differential equation. Under the control obtained, the dynamic performance of the system is much improved while accomplishing successfully the rendezvous mission of the spacecraft. Finally, a practical example is provided to show the effectiveness of the proposed control design approach.
Use of a flow deflector to protect rheophilic fish spawning grounds during hydropeaking
Authors: Bartoň Daniel , Sajdlová Zuzana , Kolařík Tomáš , Kubečka Jan , Duras Jindřich , Kortan David , Šmejkal Marek
Published: November 2022

Rheophilic fishes are one of the ecological groups of fishes declining most quickly in number due to various habitat modifications and discharge regulations. Artificial rapid increases and decreases in discharge (hydropeaking) can cause severe damage to the eggs of rheophilic fishes. We investigated whether the effects of a water increase in hydropeaking on a spawning ground may be mitigated by a deflector installed at the top of the weir that diverts flow to other sections. At the research site, rheophilic asp (Leuciscus aspius) spawn annually in early spring, and their success might be affected by hydropeaking, with base discharge ranging from 3 to 7 m3 × s−1 and peak discharge ranging from 16 to 25 m3 × s−1 occurring 4 to 7 times during the asp spawning season and egg development period. To protect the adhesive eggs from detachment during peak discharge, a flow deflector (a wooden wall at the selected part of the weir) was installed to regulate discharge on the protected spawning ground. This measure allowed normal discharge under base flow conditions. During peak flow, a significant portion of the additional water was directed to the part of the river channel where egg abundance was lower and to the mill channel, where asp spawning was not present. While the total discharge increased 4.1 times compared to the base flow, the water discharge in the protected spawning ground increased only 2.7 times. This resulted in more than half of the asp eggs being retained in the protected channel. Although the use of such a measure is limited to specific local conditions where eggs are located just downstream of the weir, it can be a valid solution in highly fragmented rivers with hydropeaking and can lead to higher recruitment of rheophilic fishes.
Modelling the dynamics of firm valuation: An assessment of impact of exchange rate fluctuations on firm value using system dynamics
Authors: Khan Aima , Qureshi Muhammad Azeem
Published: November 2022

Exchange rate volatility is a vital issue in international finance due to its effect on the value of the firm, depending on firm's exposure to the exchange rate risk. However, this impact is not clear in literature as evidence is mixed. This article analyses the impact of exchange rate fluctuations on firm value. A system dynamics‐based corporate planning model has been developed that incorporates the modules for financial and physical processes, firm valuation and exchange rate determination. Simulation results reveal that a stronger home currency leads to an increase in market price per share of the firm and vice versa. The results provide counter intuitive evidence on the impact of exchange rate on firm value and provide nonlinear feedback loop‐based explanation. The study fills the gap in literature by incorporating a systemic approach in the strategic planning process to assess the composite impact of parameter changes on key variables.
Atomic‐Scale Study on the Interaction Mechanism between Cracking and Typical Grain Boundaries in 15‐5 PH Stainless Steel
Authors: Li Bei , Jin Chunhui , Li Guoqiang , Zhao Jinhua , Chen Jinshan , Ma Lifeng , Misra R. Devesh Kumar
Published: November 2022

In order to illuminate the hindering effects induced by grain boundaries on the propagation behavior of crack with respect to 15‐5 PH stainless steel, interactions between propagated crack and typical grain boundaries, including the parent austenite grain boundary (PAGB), coincidence site lattice Σ3 grain boundary (CSL Σ3), packet grain boundary (PGB), and block grain boundary (BGB) are investigated at the atomic scale. Results indicate that the higher stress in the crack initiation (CI) stage and crack and grain boundary interaction (CGB) stage is required to drive the propagating crack in terms of the PAGB model compared to the other models, and the longest interaction time between propagated crack and established grain boundary is needed for the crack from the crack propagation (CP) stage to the CGB stage in the case of the PGB model. The PAGB and PGB are determined to be the most effective in hindering crack propagation in 15‐5 PH stainless steel.
Investigation of Multistage Oxidation Behavior of Al4SiC4 Powders with Aid of Back Propagation Artificial Neural Network
Authors: Guo Chunyu , Shi Jinzhuo , Ru Feng , Zhao Chunyang , Wang Enhui , Yang Tao , Hou Xinmei
Published: November 2022

In order to investigate the multistage oxidation behavior of aluminum silicon carbide (Al4SiC4), back propagation artificial neural network (BP‐ANN) has been trained and employed considering the oxidation temperature, time, and aspect ratio. The results denote that the BP‐ANN model can accurately and efficiently simulate the oxidation behavior of Al4SiC4 powders with different reaction laws. In addition, the extrapolation ability suggests that the BP‐ANN model can maintain a high accuracy with the coefficient of determination ≥0.801 to expand the experimental data to 1.2 times the original range. By incorporating a real physical picture model developed by the research group, the experimental data can be further expanded to 2.2 times. This study can provide a new path to recognize the oxidation behavior of materials with multistage oxidation.
Modeling and Experimental Results for Microwave Imaging of a Hip with Emphasis on the Femoral Neck
Authors: Adams Johnathan , Serano Peter , Nazarian Ara
Published: November 2022

This study investigates the potential for microwave imaging to scan the proximal femur to detect osteoporotic bone conditions. Additionally, we aim to establish more general regularities pertinent to microwave imaging at different frequencies for better penetration into the human body and the unwanted yet unavoidable transmission around the body via surface/creeping waves.

The frequency bands of interest are the UHF, L-band, and S-band. Both modeling (Ansys Electronics Desktop 2021) and experimental results will be presented. The human model employed for numerical simulations is a modified built-in Ansys non-anatomical model.
Standardizing Skullremodeling Surgery and Electrode Array Layout to Improve Tumor Treating Fields Using Computational Head Modeling and Finite Element Methods
Authors: Mikic N. , Cao F. , Hansen F. L. , Jakobsen A. M. , Thielscher A. , Korshøj A. R.
Published: November 2022

Skullremodeling surgery (SR-surgery) includes removing bone from the skull to enhance TTFields. In our phase 1 trial (NCT02893137) we tested multiple SR-configurations (craniectomy, burrholes, and skull thinning) with TTFields concluding it to be safe. To examine the efficacy, we recently initiated an investigator-initiated, randomized, comparative, multi-center phase 2 trial (NCT04223999).

To ensure uniformity, SR-surgery will be standardized to 5 burrholes of 15 mm diameter placed cross-diagonally in a 45×45 mm square above the tumor. The configuration was chosen as a combination of maximizing the overall cm3 while not compromising patient safety.

To create a standard operating procedure for the trial, we wanted to examine how the electric field was affected by this SR-surgery configuration, its location, and the electrode array placement. We created E-field simulations based on a computational head model, that mimicked a trial patient’s tumor resection cavity, residual tumor, and SR-surgery. SR-surgery was virtually applied at several locations with different electrode positions to investigate the impact on the electric field in the residual tumor tissue, resection cavity, and grey- and white matter. The electrode arrays were moved by 15-degree stepwise rotation around a central craniocaudal axis in the same horizontal plane, corresponding to 0–180 degrees for a total of 13 different positions. Control simulations without SR-surgery were also performed.

In general, we found that SR-surgery increased the electric field strength significantly in the residual tumor and resection cavity with minimal effect on the healthy white and grey matter tissue. The highest electric field values were observed in the residual tumor and resection cavity when the burrholes were placed directly above the pathological tissue and the edge electrodes of both pairs were placed on top or close to the burrholes with the reference electrode directly opposite on the head.
Peripheral Nerve Stimulation (PNS) Analysis of MRI Head Gradient Coils with Human Body Models
Authors: Hua Yihe , Yeo Desmond T. B. , Foo Thomas K. F.
Published: November 2022

The main objective of this chapter is to provide a comprehensive and intuitive introduction to MRI gradient coil related PNS modeling with human body models. We will present the fundamental concepts and analytical processes behind gradient coil-induced peripheral nerve stimulation (PNS) modeling and also show some new results of our work. We first describe the process of performing electromagnetic simulation of a gradient coil, the neurodynamic simulation of nerves, and the gradient coil design. Then, we present improvements of two existing human body models by adding more nerve trajectories in the head and upper body to reduce the discrepancies between the simulated and measured results for PNS thresholds in head gradient coils. Further, we apply the modified human body models to analyze three folded and non-folded gradient coils and reveal the relationship between the eddy current flow in the human body and the gradient coil wire pattern and its impact on the PNS. We also show the connection between concomitant fields and PNS and assess the accuracy of PNS calculations in human body models with simplified tissue properties. Finally, we give our thoughts on the future direction of this work.
Evaluation and Comparison of Simulated Electric Field Differences Using Three Image Segmentation Methods for TMS
Authors: Zaidi Tayeb , Fujimoto Kyoko
Published: November 2022

Computational electromagnetic modeling is a powerful technique to evaluate the effects of electrical stimulation of the human brain. The results of these simulations can vary based on the segmentation of the head and brain generated from the patient images. Using an existing boundary element fast multipole method (BEM-FMM) electromagnetic solver, this work compares the simulated electric field differences resulted by the three segmentation methods. A transcranial magnetic stimulation (TMS) coil targeting both the primary motor cortex and the dorsolateral prefrontal cortex (DLPFC) was simulated. Average field differences were small among the three methods (2% for motor cortex, 3% for DLPFC) and the average field differences in the regions directly surrounding the target stimulation point were 5% for the motor cortex and 2% for DLPFC. More studies evaluating different coils and other segmentation options may further improve the computational modeling for robust TMS treatment.
RF-induced Heating Near Active Implanted Medical Devices in MRI: Impact of Tissue Simulating Medium
Authors: Brown James E. , Stadnik Paul J. , Von Arx Jeffrey A. , Muessig Dirk
Published: November 2022

Recent advances in the MR conditional safety assessment of active implantable medical devices (AIMDs) have begun providing guidelines in the development of transfer functions for evaluating risk to the patient due to RF-induced heating. This work introduces the complexity of the analysis of RF-induced heating and explores the impact of the computational human model (CHM) on the resulting analysis. Through historical analysis techniques, simplified structures, and real medical device geometries, the interaction of the AIMD lead with the tissue simulating medium (TSM) can be better understood. Finally, a general guiding principle for MR manufacturers is identified, whereby the thickness of the lead insulation can be used to determine the appropriate TSM for the most accuratein vivopredictions of RF-induced heating.
Elements of Identity in Conflict
Authors: Ricarte Joana
Published: November 2022

This chapter dives deeper into the theoretical framework proposed in this book by identifying, characterizing and proposing concrete indicators at the observable level for assessing and analyzing theelementsof identity in conflict. The argument developed is that an empirical examination of the processes of identity building in protracted conflicts shows that these feature two main elements—and coexisting dynamics—which can be seen as opposing poles that might contribute to deepening the conflict or promoting its transformation instead. By identifying the dimensions and observable indicators that allow for an assessment of these processes of dehumanization and peace-less reconciliation, this chapter offers a tool for empirical analyses of protracted conflicts and policy development toward their positive transformation.
On sets of linear forms of maximal complexity
Authors: Kaminski Michael , Shparlinski Igor E. , Waldschmidt Michel
Published: November 2022

We present a uniform description of sets of m linear forms
in n variables over the field of rational numbers whose computation
requires m(n – 1) additions.
Patient-reported impairment following TKA is reduced when a computationally simulated predicted ideal alignment is achieved
Authors: Twiggs Joshua , Miles Brad , Parker David , Liu David , Shimmin Andrew , Fritsch Brett , Roe Justin , Baré Jonathan , Solomon Michael , Dickison David , McMahon Stephen , Boyle Richard , Walter Len
Published: November 2022

Purpose

Joint dynamics following Total Knee Arthroplasty (TKA) may influence patient-reported outcome. Simulations allow many knee alignment approaches to a single patient to be considered prior to surgery. The simulated kinematics can be matched to patient-reported outcome to predict kinematic patterns most likely to give the best outcome. This study aims to validate one such previously developed algorithm based on a simulated deep knee bend (the Dynamic Knee Score, DKS).

Methods

1074 TKA patients with pre- and post-operative Computerised Tomography (CT) scans and 12-month post-operative Knee Injury and Osteoarthritis Outcomes (KOOS) Scores were identified from the 360 Med Care Joint Registry. Landmarking and registration of implant position was performed on all CT scans, and each of the achieved TKAs was computationally simulated and received a predictive outcome score from the DKS. In addition, a set of potential alternative surgical plans which might have been followed were simulated. Comparison of patient-reported issues and DKS score was evaluated in a counter-factual study design.

Results

Patient-reported impairment with the knee catching and squatting was shown to be 30% lower (p = 0.005) and 22% lower (p = 0.026) in patients where the best possible DKS result was the one surgically achieved. Similar findings were found relating attainment of the best tibial slope and posterior femoral resection DKS plans to patient-reported difficulty straightening the knee (40% less likely, p < 0.001) and descending stairs (35% less likely, p = 0.006).

Conclusion

The DKS has been shown to correlate with presence of patient-reported impairments post-TKA and the resultant algorithm can be applied in a pre-operative planning setting. Outcome optimization in the future may come from patient-specific selection of an alignment strategy and simulations may be a technological enabler of this trend.

Level of evidence.

III (Retrospective Cohort Study).
Fair evaluation of classifier predictive performance based on binary confusion matrix
Authors: Vanacore Amalia , Pellegrino Maria Sole , Ciardiello Armando
Published: November 2022

Evaluating the ability of a classifier to make predictions on unseen data and increasing it by tweaking the learning algorithm are two of the main reasons motivating the evaluation of classifier predictive performance. In this study the behavior of Balanced $$AC_1$$

A

C
1

 — a novel classifier accuracy measure — is investigated under different class imbalance conditions via a Monte Carlo simulation. The behavior of Balanced $$AC_1$$

A

C
1

is compared against that of several well-known performance measures based on binary confusion matrix. Study results reveal the suitability of Balanced $$AC_1$$

A

C
1

with both balanced and imbalanced data sets. A real example of the effects of class imbalance on the behavior of the investigated classifier performance measures is provided by comparing the performance of several machine learning algorithms in a churn prediction problem.
Additive adjudication of conflicting claims
Authors: García-Segarra Jaume , Ginés-Vilar Miguel
Published: November 2022

In a “claims problem” (O’Neill 1982), a group of individuals have claims on a resource but its endowment is not sufficient to honour all of the claims. We examine the following question: If a claims problem can be decomposed into smaller claims problems, can the solutions of these smaller problems be added to obtain the solution of the original problem? A natural condition for this decomposition is that the solution to each of the smaller problems is non-degenerate, assigning positive awards to each claimant. We identify the only consistent and endowment monotonic adjudication rules satisfying this property; they are generalizations of the canonical “constrained equal losses rule” sorting claimants into priority classes and distributing the amount available to each class using a weighted constrained equal losses rule. The constrained equal losses rule is the only symmetric rule in this family of rules.
Network disruption and the common-enemy effect
Authors: Hoyer Britta , De Jaegher Kris
Published: November 2022

We study the effect of a common enemy on the connections-model of network formation, where self-interested players can use links to build a network, knowing that they face a common enemy who can disrupt the links or nodes of the network. The goal of the common enemy is to minimize the sum of the benefits players obtain from the network. We find that for large linking costs, introducing such a common enemy can lead to the formation of pairwise stable and efficient networks which would not be pairwise stable without the threat of disruption. The reason is the large reduction in payoffs caused by disruption as soon as one player fails to maintain a link. However, we also find that for small linking costs, the empty network is pairwise stable under disruption, whereas it is not in the absence of disruption. The reason is that in the presence of disruption a link that is unilaterally formed is automatically targeted (or one of the players forming the link is automatically targeted). While the common enemy can thus have a positive effect on the incentives of the players to form an efficient network, it can also lead to the disintegration of the network.
Existence and uniqueness of Nash equilibrium in discontinuous Bertrand games: a complete characterization
Authors: Edwards R. A. , Routledge R. R.
Published: November 2022

Since (Reny in Econometrica 67:1029–1056, 1999) a substantial body of research has considered what conditions are sufficient for the existence of a pure strategy Nash equilibrium in games with discontinuous payoffs. This work analyzes a general Bertrand game, with convex costs and an arbitrary sharing rule at price ties, in which tied payoffs may be greater than non-tied payoffs when both are positive. On this domain, necessary and sufficient conditions for (i) the existence of equilibrium (ii) the uniqueness of equilibrium are presented. The conditions are intuitively easy to understand and centre around the relationships between intervals of real numbers determined by the primitives of the model.
Verapamil inhibits Kir2.3 channels by binding to the pore and interfering with PIP2 binding
Authors: Xynogalos Panagiotis , Rahm Ann-Kathrin , Fried Sebastian , Chasan Safak , Scherer Daniel , Seyler Claudia , Katus Hugo A. , Frey Norbert , Zitron Edgar
Published: November 2022

The inwardly rectifying potassium current of the cardiomyocyte (IK1) is the main determinant of the resting potential. Ion channels Kir2.1, Kir2.2, and Kir2.3 form tetramers and are the molecular correlate of macroscopic IK1 current. Verapamil is an antiarrhythmic drug used to suppress atrial and ventricular arrhythmias. Its primary mechanism of action is via blocking calcium channels. In addition, it has been demonstrated to block IK1 current and the Kir2.1 subunit. Its effect on other subunits that contribute to IK1 current has not been studied to date. We therefore analyzed the effect of verapamil on the Kir channels 2.1, 2.2, and 2.3 in the Xenopus oocyte expression system. Kir2.1, Kir2.2, and Kir2.3 channels were heterologously expressed in Xenopus oocytes. Respective currents were measured with the voltage clamp technique and the effect of verapamil on the current was measured. At a concentration of 300 µM, verapamil inhibited Kir2.1 channels by 41.36% ± 2.7 of the initial current, Kir2.2 channels by 16.51 ± 3.6%, and Kir2.3 by 69.98 ± 4.2%. As a verapamil effect on kir2.3 was a previously unknown finding, we analyzed this effect further. At wash in with 300 µM verapamil, the maximal effect was seen within 20 min of the infusion. After washing out with control solution, there was only a partial current recovery. The current reduction from verapamil was the same at − 120 mV (73.2 ± 3.7%), − 40 mV (85.5 ± 6.5%), and 0 mV (61.5 ± 10.6%) implying no voltage dependency of the block. Using site directed mutations in putative binding sites, we demonstrated a decrease of effect with pore mutant E291A and absence of verapamil effect for D251A. With mutant I214L, which shows a stronger affinity for PIP2 binding, we observed a normalized current reduction to 61.9 ± 0.06% of the control current, which was significantly less pronounced compared to wild type channels. Verapamil blocks Kir2.1, Kir2.2, and Kir2.3 subunits. In Kir2.3, blockade is dependent on sites E291 and D251 and interferes with activation of the channel via PIP2. Interference with these sites and with PIP2 binding has also been described for other Kir channels blocking drugs. As Kir2.3 is preferentially expressed in atrium, a selective Kir2.3 blocking agent would constitute an interesting antiarrhythmic concept.
Rapid LC–MS assay for targeted metabolite quantification by serial injection into isocratic gradients
Authors: Groves Ryan A. , Chan Carly C. Y. , Wildman Spencer D. , Gregson Daniel B. , Rydzak Thomas , Lewis Ian A.
Published: November 2022

Liquid chromatography mass spectrometry (LC–MS) has emerged as a mainstream strategy for metabolomics analyses. One advantage of LC–MS is that it can serve both as a biomarker discovery tool and as a platform for clinical diagnostics. Consequently, it offers an exciting opportunity to potentially transition research studies into real-world clinical tools. One important distinction between research versus diagnostics-based applications of LC–MS is throughput. Clinical LC–MS must enable quantitative analyses of target molecules in hundreds or thousands of samples each day. Currently, the throughput of these clinical applications is limited by the chromatographic gradient lengths, which—when analyzing complex metabolomics samples—are difficult to conduct in under ~ 3 min per sample without introducing serious quantitative analysis problems. To address this shortcoming, we developed sequential quantification using isotope dilution (SQUID), an analytical strategy that combines serial sample injections into a continuous isocratic mobile phase to maximize throughput. SQUID uses internal isotope-labelled standards to correct for changes in LC–MS response factors over time. We show that SQUID can detect microbial polyamines in human urine specimens (lower limit of quantification; LLOQ = 106 nM) with less than 0.019 normalized root mean square error. Moreover, we show that samples can be analyzed in as little as 57 s. We propose SQUID as a new, high-throughput LC–MS tool for quantifying small sets of target biomarkers across large cohorts.

Graphical Abstract
Prevalence trends and individual patterns of ADHD medication use in pregnancy in Norway and Sweden, 2010–2019
Authors: Cohen Jacqueline M. , Srinivas Chaitra , Furu Kari , Cesta Carolyn E. , Reutfors Johan , Karlstad Øystein
Published: November 2022

Purpose

This study aimed to describe recent trends in ADHD medication use in pregnancy in Norway and Sweden, including prevalence, individual characteristics, and patterns of use.

Methods

We studied ADHD medication use (amphetamine, dexamphetamine, methylphenidate, atomoxetine, lisdexamfetamine, guanfacine) by year and age in pregnancies from 2010 to 2019 identified from the medical birth registers (gestational age ≥ 22 weeks) linked to prescribed drug registers (Norway,N = 577,116; Sweden,N = 1,118,988). We compared characteristics of those who used any ADHD medication in pregnancy to no use in pregnancy. Discontinuation was defined as no use after first trimester.

Results

ADHD medication use increased from 2010 to 2019 by 3.0 users per 1000 pregnancies in Norway (from 2.5 to 5.5/1000) and by 6.3 per 1000 in Sweden (from 1.6 to 7.9/1000), mainly driven by methylphenidate and since 2015 by lisdexamfetamine. Medication use has increased among pregnant individuals of all age groups, with higher use among the youngest. Pregnant individuals who used ADHD medication were less likely to be married/cohabiting, more likely be nulliparous and to smoke. They had particularly high use of co-medication with antidepressants, anxiolytics/hypnotics, and opioids: 42% in Norway and 65% in Sweden used at least one additional class of psychotropic medication. Most individuals discontinued ADHD medication in pregnancy (85% Norway, 78% Sweden).

Conclusion

ADHD medication use during pregnancy increased in Norway and Sweden in the last decade. However, discontinuation rates during pregnancy were high. Those who used ADHD medication had more risk factors for pregnancy complications including low parity, smoking, and other psychotropic drug use.
Environmental and Anthropogenic Factors Shape the Skin Bacterial Communities of a Semi-Arid Amphibian Species
Authors: Bates K. A. , Friesen J. , Loyau A. , Butler H. , Vredenburg V. T. , Laufer J. , Chatzinotas A. , Schmeller D. S.
Published: November 2022

The amphibian skin microbiome is important in maintaining host health, but is vulnerable to perturbation from changes in biotic and abiotic conditions. Anthropogenic habitat disturbance and emerging infectious diseases are both potential disrupters of the skin microbiome, in addition to being major drivers of amphibian decline globally. We investigated how host environment (hydrology, habitat disturbance), pathogen presence, and host biology (life stage) impact the skin microbiome of wild Dhofar toads (Duttaphrynus dhufarensis) in Oman. We detected ranavirus (but not Batrachochytrium dendrobatidis) across all sampling sites, constituting the first report of this pathogen in Oman, with reduced prevalence in disturbed sites. We show that skin microbiome beta diversity is driven by host life stage, water source, and habitat disturbance, but not ranavirus infection. Finally, although trends in bacterial diversity and differential abundance were evident in disturbed versus undisturbed sites, bacterial co-occurrence patterns determined through network analyses revealed high site specificity. Our results therefore provide support for amphibian skin microbiome diversity and taxa abundance being associated with habitat disturbance, with bacterial co-occurrence (and likely broader aspects of microbial community ecology) being largely site specific.
Upper tract urothelial carcinoma in Germany: epidemiological data and surgical treatment trends in a total population analysis from 2006 to 2019
Authors: Herout Roman , Baunacke Martin , Flegar Luka , Borkowetz Angelika , Reicherz Alina , Koch Rainer , Kraywinkel Klaus , Thomas Christian , Groeben Christer , Huber Johannes
Published: November 2022

Purpose

To report contemporary epidemiological data and treatment trends for upper tract urothelial carcinoma (UTUC) in Germany over a 14-year period.

Methods

We analyzed data from the nationwide German hospital billing database and the German cancer registry from 2006 to 2018/2019. The significance of changes over time was evaluated via regression analysis. Survival outcomes were calculated using the Kaplan–Meier method.

Results

There was a non-significant increase in the age-standardized incidence rate from 2.5/100,000 in 2006 to 2.9/100.000 in 2018. 13% of patients presented with lymph node metastasis and 7.6% of patients presented with distant metastasis at primary diagnosis. The 5-year overall survival was estimated at 45% and the 10-year overall survival at 32%. Endoscopic biopsies of the renal pelvis and ureter as well as ureteroscopies with excision/destruction of UTUC all increased significantly over the study period. The number of radical nephroureterectomies (RNU) for UTUC steadily increased from 1643 cases in 2006 to 2238 cases in 2019 (p < 0.005) with a shift from open surgery towards minimally invasive surgery. Complex reconstructive procedures like ileal ureter replacement or autotransplantation are rarely performed for urothelial carcinoma of the ureter.

Conclusion

Diagnostic and therapeutic procedures for UTUC have increased and minimally invasive nephroureterectomy is the predominant approach concerning radical surgery in 2019.
Histogram equalization using a selective filter
Authors: Dyke Roberto M. , Hormann Kai
Published: November 2022

Many popular modern image processing software packages implement a naïve form of histogram equalization. This implementation is known to produce histograms that are not truly uniform. While exact histogram equalization techniques exist, these may produce undesirable artifacts in some scenarios. In this paper we consider the link between the established continuous theory for global histogram equalization and its discrete implementation, and we formulate a novel histogram equalization technique that builds upon and considerably improves the naïve approach. We show that we can linearly interpolate the cumulative distribution of a low-bit image by approximately dequantizing its intensities using a selective box filter. This helps to distribute the intensities more evenly. The proposed algorithm is subsequently evaluated and compared with existing works in the literature. We find that the method is capable of producing an equalized histogram that has a high entropy, while distances between similar intensities are preserved. The described approach has implications on several related image processing problems, e.g., edge detection.
Real-world comparative effectiveness of ARNI versus ACEi/ARB in HF with reduced or mildly reduced ejection fraction
Authors: Fu Michael , Pivodic Aldina , Käck Oskar , Costa-Scharplatz Madlaina , Dahlström Ulf , Lund Lars H.
Published: November 2022

Aims

Sacubitril/valsartan is a first-in-class angiotensin receptor–neprilysin inhibitor (ARNI) with a class-1 guideline recommendation. We assessed the real-world effectiveness of ARNI versus angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB) on all-cause and cardiovascular (CV)-related mortality and hospitalizations in heart failure (HF) with reduced or mildly reduced ejection fraction (EF).

Methods

Patient-level clinical, laboratory, drug dispensation, hospitalization, and mortality data were derived from the Swedish Heart Failure Registry (SwedeHF) and interlinked databases (1 April 2016–31 December 2020). Eligible ARNI:ACEi/ARB patients (n = 7275:24,604) had a left ventricular EF < 50%. Mortality and hospitalizations with ARNI (≤ 3 months pre-/post-1 April 2016 index [SwedeHF]; n = 1506) versus ACEi/ARB (≤ 3 months post-index; n = 17,108) were assessed using propensity score matching (1:1 ratio) with clinical variables, and sensitivity analysis (1:2/1:3 with, and 1:2 without clinical variables).

Results

ARNI induced a 23% reduction in all-cause mortality versus ACEi/ARB (1:1 hazard ratio [HR; 95% confidence interval (CI)]: 0.77 [0.63–0.95], p = 0.013), and a non-significant 23% relative risk reduction in CV-related mortality (0.77 [0.54–1.09], p = 0.13), but no difference in all-cause or CV-related hospitalization (1.02 [0.91–1.13]; p = 0.76; 1.01 [0.91–1.15]; p = 0.84, respectively). Sensitivity analyses confirmed all-cause mortality was reduced for ARNI versus ACEi/ARB (HR 0.90 [95% CI 0.82–0.99], p = 0.026), but not CV-related mortality (HR 1.04 [95% CI 0.89–1.22], p = 0.63).

Conclusions

In this nationwide real-world study including a population of patients with HF with reduced or mildly reduced EF, ARNI as part of guideline-led Swedish clinical practice was associated with a statistically significant relative risk reduction in all-cause mortality compared with ACEi/ARB.
Beta-3 adrenergic receptor overexpression reverses aortic stenosis–induced heart failure and restores balanced mitochondrial dynamics
Authors: Pun-García Andrés , Clemente-Moragón Agustín , Villena-Gutierrez Rocio , Gómez Monica , Sanz-Rosa David , Díaz-Guerra Anabel , Prados Belén , Medina Juan Pablo , Montó Fermí , Ivorra Maria Dolores , Márquez-López Cristina , Cannavo Alessandro , Bernal Juan A. , Koch Walter J. , Fuster Valentin , de la Pompa José Luis , Oliver Eduardo , Ibanez Borja
Published: November 2022

Aortic stenosis (AS) is associated with left ventricular (LV) hypertrophy and heart failure (HF). There is a lack of therapies able to prevent/revert AS-induced HF. Beta3 adrenergic receptor (β3AR) signaling is beneficial in several forms of HF. Here, we studied the potential beneficial effect of β3AR overexpression on AS-induced HF. Selective β3AR stimulation had a positive inotropic effect. Transgenic mice constitutively overexpressing human β3AR in the heart (c-hβ3tg) were protected from the development of HF in response to induced AS, and against cardiomyocyte mitochondrial dysfunction (fragmented mitochondria with remodeled cristae and metabolic reprogramming featuring altered substrate use). Similar beneficial effects were observed in wild-type mice inoculated with adeno-associated virus (AAV9) inducing cardiac-specific overexpression of human β3AR before AS induction. Moreover, AAV9-hβ3AR injection into wild-type mice at late disease stages, when cardiac hypertrophy and metabolic reprogramming are already advanced, reversed the HF phenotype and restored balanced mitochondrial dynamics, demonstrating the potential of gene-therapy-mediated β3AR overexpression in AS. Mice with cardiac specific ablation of Yme1l (cYKO), characterized by fragmented mitochondria, showed an increased mortality upon AS challenge. AAV9-hβ3AR injection in these mice before AS induction reverted the fragmented mitochondria phenotype and rescued them from death. In conclusion, our results step out that β3AR overexpression might have translational potential as a therapeutic strategy in AS–induced HF.
Conceptualization, use, and outcomes associated with compassion in the care of people with multiple sclerosis: a scoping review
Authors: Simpson Robert , Posa Stephanie , Bruno Tania , Simpson Sharon , Wasilewski Marina B. , Robinson Lawrence R. , Munce Sarah , Bayley Mark , Feinstein Anthony
Published: November 2022

Objective

Compassion is widely regarded as an important component of high-quality healthcare. However, its conceptualization, use, and associated outcomes in the care of people with multiple sclerosis (PwMS) have not been synthesized. The aim of this review is to scope the peer reviewed academic literature on the conceptualization, use, and outcomes associated with compassion in the care of PwMS.

Methods

Studies were eligible for inclusion if reporting primary research data from quantitative, qualitative, or mixed-methods studies on the conceptualization, use, and outcomes associated with compassion in the care of PwMS. Relevant studies were identified through searching five electronic databases (CINAHL, Cochrane Library, EMBASE, MEDLINE, and PsycINFO) in January 2022. We followed the guidance outlined in the Joanna Briggs Institute (JBI) manual for evidence synthesis, and also referred to the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews Checklist (PRISMA-ScR). Simple descriptive methods were used to chart quantitative findings, and a descriptive approach with basic content analysis was employed to describe qualitative findings.

Results

Fifteen studies were included (participant n = 1722): eight quantitative, six mixed-methods, one exclusively qualitative. Synthesized qualitative data revealed that PwMS conceptualize compassion as involving self-kindness, agency, and acceptance. PwMS report using self-compassion in response to unpleasant sensations and experiences. Quantitative findings suggest that compassion may mediate benefit finding, reduced distress, and improved quality of life (QoL) in PwMS, that those with the condition may become more compassionate through time, and that self-compassion specifically can be increased through training in mindfulness. In this context, greater self-compassion in PwMS correlates with less depression and fatigue, better resilience and QoL. Among studies, self-compassion was the most common outcome measure for PwMS.

Conclusions

A nascent literature exists on the conceptualization, use, and outcomes associated with compassion in the care of PwMS. Further research is required to better understand what compassion means to PwMS and those caring for them. However, self-compassion can be cultivated among PwMS and may be helpful for managing unpleasant somatic symptoms and in benefit finding. Impact on other health outcomes is less clear. The use of compassion by health care providers in the care of PwMS is unstudied.
Antiplatelet and anticoagulant therapy in patients with submacular hemorrhage caused by neovascular age-related macular degeneration
Authors: Weber Constance , Bertelsmann Maria , Kiy Zoe , Stasik Isabel , Holz Frank G. , Liegl Raffael
Published: November 2022

Purpose

Patients with extensive submacular hemorrhage (SMH) caused by age-related macular degeneration (AMD) have a poor visual prognosis despite surgical intervention. Systemic blood-thinning drugs, which are commonly prescribed in the same age group, are known to increase the risk of severe hemorrhage in many parts of the body. This study aimed to investigate whether systemic blood-thinning drugs have an impact on the severity of SMH and if there are differences between the different types of blood-thinning medication.

Methods

We reviewed the medical records of patients who suffered from surgically treated SMH between 2020 and 2022. All patients received a full ophthalmologic examination upon presentation including best-corrected visual acuity (BCVA) and optical coherence tomography. Other characteristics that were recorded included size of hemorrhage, blood-thinning therapy, and reason for intake.

Results

A total of 115 patients with a mean age of 82 years were included in this retrospective analysis. Eighty-three patients (72.2%) were on blood-thinning therapy. The mean size of SMH was 32.01 mm2. Mean BCVA at initial presentation was 1.63 logMAR and 1.59 logMAR 1 year after surgery. The size of SMH was significantly larger in patients on blood-thinning medication (35.92 mm2 vs. 21.91 mm2) (p = 0.001) and their BCVA postoperatively was worse with 1.68 logMAR compared to 1.30 logMAR after 1 year (p = 0.503). Patients with vitamin K antagonists had larger SMH size and worse outcomes regarding BCVA compared to direct oral anticoagulants.

Conclusion

Blood thinners in patients with AMD affect the severity of SMH. Consequently, the indication for their intake should be critically evaluated.
When is a postmortem examination carried out? A retrospective analysis of all Swedish deaths 1999–2018
Authors: Tamsen Fredrik , Alafuzoff Irina
Published: November 2022

The objective of this study was to assess who is merited an autopsy in Sweden. Data from the Swedish cause of death (COD) registry over a period of 20 years was retrieved and analysed. A multinominal logistic regression analysis was performed to identify the variables that were most strongly associated with the performance of a clinical or forensic autopsy (CA/FA).

A definite COD, i.e. a COD based on autopsy findings, was registered in 12.6% of all deceased during the investigated period. In the remaining cases, the COD was presumed by the clinicians. Being male, born in the Nordic region, dying in a private residence, and unnatural death were most strongly associated with the performance of CA/FA. In contrast, being female, dying from dementia, dying at a nursing home, being born outside of Europe, or living in a small city or rural area seldom led to the performance of CA/FA.

The above is certainly surprising as an autopsy provides an opportunity to investigate the cause of death, validate clinical diagnoses, detect unexpected aberrations, audit health care, and provide feedback to clinicians to facilitate their continuing education.
Fitness, body composition, and metabolic risk scores in children and adolescents: the UP&DOWN study
Authors: Sánchez-Delgado Alejandro , Pérez-Bey Alejandro , Izquierdo-Gómez Rocío , Jimenez-Iglesias José , Marcos Ascensión , Gómez-Martínez Sonia , Girela-Rejón María José , Veiga Oscar L , Castro-Piñero José
Published: November 2022

We aimed to analyse the longitudinal association between physical fitness (PF) and body composition (BC) with a metabolic risk score (Met4) in children and adolescents and to elucidate whether the association between PF and Met4 differs when using relativized or absolute fitness variables. A total of 188 children (86 females) and 195 adolescents (97 females) were included. Cardiorespiratory fitness (CRF) was determined by the 20-m shuttle run test, and muscular fitness (MF) was determined by hand grip and standing long jump tests. Height and weight were measured, and the body mass index (Kg/m2) was calculated. Triceps and subscapular skinfolds were assessed to compute body fat percentage. Met4 was computed from systolic blood pressure, triglycerides, high-density lipoprotein cholesterol, and glucose levels. Relative CRF was longitudinally and negatively associated with Met4 in female children (β =  −0.031, p = 0.025), while absolute CRF was positively associated with Met4 in male children and adolescents (β = 0.000, p < 0.05). Relative upper and lower-body MF were longitudinally and negatively associated with Met4 in female adolescents (β =  −1.347, β =  −0.005, p < 0.05), while absolute lower-body MF was positively associated with Met4 in male children (β = 0.000, p = 0.019). BC was longitudinally and positively associated with Met4 in male children (β-ranging from 0.011 to 0.055, all p < 0.05) and male adolescents (β-ranging from 0.011 to 0.046, all p < 0.05).

  Conclusion: BC is more strongly associated with Met4 than PF in children and adolescents. An optimal body weight status should be considered the main objective of health-promoting programs at childhood and adolescence. Furthermore, the way of expressing the fitness variables determines the direction of the association with Met4.

What is Known:• Physical fitness is an important health indicator in children and adolescents, with great amount of previous evidence supporting the preventive role of maintaining optimal levels of both cardiorespiratory and muscular fitness for future cardiometabolic issues.

What is New:• The way of reporting physical fitness variables can affect the associations between physical fitness features and cardiometabolic outcomes. Since body composition variables have a great impact on both physical fitness and cardiometabolic health, relativizing physical fitness performance by body composition could lead to erroneous conclusions.