bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of organizational compassion in health care on clinicians: A scoping review
Authors: Pestian Teresa , Awtrey Eli , Kanov Jason , Winick Naomi , Thienprayoon Rachel
Published: June 2023

Background

The unprecedented exodus of workers from the healthcare system is a patient safety crisis. Organizational compassion in health care is the proactive, systematic, and continuous identification, alleviation, and prevention of all sources of suffering.

Aims

This scoping review aimed to describe the evidence regarding the impact of organizational compassion on clinicians, identify gaps, and provide recommendations for future research.

Methods

A comprehensive librarian‐assisted database search was conducted. Databases searched were PubMed, SCOPUS, EMBASE, Web of Science, PsychInfo, and Business Source Complete. Combinations of search terms regarding health care, compassion, organizational compassion, and workplace suffering were used. The search strategy was limited to English language articles and those published between 2000 and 2021.

Results

Database search yielded 781 articles. After removing duplicates, 468 were screened by title and abstract, and 313 were excluded. One‐hundred and fifty‐five underwent full‐text screening, and 137 were removed, leaving 18 eligible articles, two of which were set in the United States. Ten articles evaluated barriers or facilitators to organizational compassion, four evaluated elements of compassionate leadership, and four evaluated the Schwartz Center Rounds intervention. Several described the need to create systems that are compassionate to clinicians. Lack of time, support staff, and resources impeded the delivery of such interventions.

Linking evidence to action

Little research has been done to understand and evaluate the impact of compassion on US clinicians. Given the workforce crisis in American health care and the potential positive impact of increasing compassion for clinicians, there is an urgent need for researchers and healthcare administrators to fill this gap.
More airway smooth muscle in males versus females in a mouse model of asthma: A blessing in disguise?
Authors: Gill Rebecka , Rojas‐Ruiz Andrés , Boucher Magali , Henry Cyndi , Bossé Ynuk
Published: June 2023

Mouse models are helpful in unveiling the mechanisms underlying sex disparities in asthma. In comparison to their female counterparts, male mice are hyperresponsive to inhaled methacholine, a cardinal feature of asthma that contributes to its symptoms. The physiological details and the structural underpinnings of this hyperresponsiveness in males are currently unknown. Herein, BALB/c mice were exposed intranasally to either saline or house dust mite once daily for 10 consecutive days to induce experimental asthma. Twenty‐four hours after the last exposure, respiratory mechanics were measured at baseline and after a single dose of inhaled methacholine that was adjusted to trigger the same degree of bronchoconstriction in both sexes (it was twice as high in females). Bronchoalveolar lavages were then collected, and the lungs were processed for histology. House dust mite increased the number of inflammatory cells in bronchoalveolar lavages to the same extent in both sexes (asthma,P = 0.0005; sex,P = 0.96). The methacholine response was also markedly increased by asthma in both sexes (e.g.,P = 0.0002 for asthma on the methacholine‐induced bronchoconstriction). However, for a well‐matched bronchoconstriction between sexes, the increase in hysteresivity, an indicator of airway narrowing heterogeneity, was attenuated in males for both control and asthmatic mice (sex,P = 0.002). The content of airway smooth muscle was not affected by asthma but was greater in males (asthma,P = 0.31; sex,P< 0.0001). These results provide further insights regarding an important sex disparity in mouse models of asthma. The increased amount of airway smooth muscle in males might contribute functionally to their greater methacholine response and, possibly, to their decreased propensity for airway narrowing heterogeneity.
Dramatic Amplification of the Flexoelectric Effect in Snapping Surfaces
Authors: Chen Lingling , Xing Xinyu , Zhao Chuo , Yang Shengyou
Published: June 2023

Flexoelectricity exists in all inhomogeneously deformed dielectric materials and is of great interest in engineering science, especially in microelectromechanical systems. However, the flexoelectricity is relatively small compared to the commonly known piezoelectricity. How to produce a considerably large flexoelectric effect and how to apply the effect to a large scale have concerned people for a long time. In this paper, we creatively amplify the flexoelectric effect without decreasing the structure scale by harnessing the electromechanical instability—the snap-through instability—of a curved dielectric plate subjected to a concentrated load. We formulate the electrostatic energy of the system and obtain the governing equations by taking the first variation of the free energy. In the analysis, we find that the thickness of the plate and the initial configuration affect the onset of the snap-through. Beyond that, we notice that flexoelectricity can lower the critical load of the snap-through instability. Importantly, we find that a large flexoelectricity can be generated by harnessing the instability. For a dielectric plate with thickness 2 × 10−7 m, the effective electromechanical coefficient is equal to 35 pC/N in the beginning; however, by using the instability, the effective coefficient can be increased to as high as 740 pC/N, which is 21 times higher after the instability. In the end, we tune the electromechanical behaviors by designing the curved plate’s thickness and configuration. This paper contributes to our understanding of the amplification of flexoelectric effects by harnessing snapping surfaces.
Design and Analysis of a Six-Degree-of-Freedom Microsurgical Instruments Based on Rigid-Flexible Coupling Multi-Body System
Authors: Wang Xuewen , Yu Yang , Yang Jinhe , Xu Zhenbang , Liu Haipeng
Published: June 2023

In order to improve the operational accuracy of microsurgical instruments and increase the success rate of surgery, a six-degree-of-freedom microsurgical instrument is designed and analyzed based on a rigid-flexible coupling multi-body system. First, an improved kinematic modeling method is proposed based on the pseudo-rigid body theory. Second, a rigid-flexible coupling simulation system is built to analyze the error sources in terms of the remote center of motion, preload, and side load. Then, the function of motion scaling, the accuracy of kinematic modeling, and the validity of the workspace are demonstrated by analyzing the workspace. In addition, the maximum stress is analyzed to ensure the safety and reliability of the application. The analysis results show that the improved kinematic modeling method improves the positioning accuracy by more than two times, and the root mean square error at the tool tip of the microsurgical instrument does not exceed 1 μm under a side load of 0.1 N. Finally, the experimental results show that the improved kinematic modeling method has higher pointing accuracy, and the maximum error does not exceed 10 μm. The designed microsurgical instrument can meet the requirements of surgical operations.
Data-Driven Dynamics Modeling and Control Strategy for a Planar n-DOF Cable-Driven Parallel Robot Driven by n + 1 Cables Allowing Collisions
Authors: Xu Genyuan , Zhu Haoda , Xiong Hao , Lou Yunjiang
Published: June 2023

Scholars have proposed to allow collisions of cables with the base, the end-effector, or obstacles to expand the workspace of cable-driven parallel robots (CDPRs) in recent years. However, allowing collisions also leads to new challenges in kinematics and dynamics modeling for CDPRs. To this end, this article focuses on a planar fully constrained n-degree-of-freedom (DOF) CDPR driven by n + 1 cables allowing collisions and develops a data-driven dynamics modeling strategy. The data-driven dynamics modeling strategy can address the collisions and optimal tension distribution issues simultaneously. Based on the data-driven dynamics modeling strategy, this article proposes a data-driven dynamics-based control strategy for the planar CDPR allowing collisions. A planar two-DOF CDPR prototype driven by three cables is established to evaluate the data-driven dynamics modeling strategy and data-driven dynamics-based control strategy.
Design and Validation of a Nonparasitic 2R1T Parallel Hand-Held Prostate Biopsy Robot With Remote Center of Motion
Authors: Jiang Wenhe , Wu Dongmei , Dong Wei , Ding Jiajun , Ye Zhichao , Zeng Pei , Gao Yongzhuo
Published: June 2023

An increasing number of grounded robots are being used in prostate interventions to improve clinical outcomes, but their large size and high-cost limit their popularity. Thus, we present a hand-held 3-degree-of-freedom (DoF) parallel robot with remote center of motion (RCM) for minimally invasive prostate biopsy applications, combining the flexibility of hand-held devices with the precision of robotic assistance. First, the kinematic structure of robotic assistance is introduced according to its design requirements. Then, the kinematic analysis of robotic assistance is carried out by using a simplified kinematic model. The kinematic parameters are designed according to the desired workspace. A prototype has been developed and validated in animal experiments. Twenty beagles of different sizes were selected for the robot-assisted and controlled experiments, resulting in target errors of 3.30 ± 1.63 mm and 5.40 ± 1.76 mm, respectively. The error of robot-assisted experiments was significantly better than in controlled experiments. Preliminary animal tests have demonstrated that the hand-held robot can improve the accuracy of free-hand biopsy punctures.
Data-Driven Approaches for Bead Geometry Prediction Via Melt Pool Monitoring
Authors: Alexander Zoe , Feldhausen Thomas , Saleeby Kyle , Kurfess Thomas , Fu Katherine , Saldaña Christopher
Published: June 2023

In the realm of additive manufacturing, the selection of process parameters to avoid over and under deposition entails a time-consuming and resource-intensive trial-and-error approach. Given the distinct characteristics of each part geometry, there is a pressing need for advancing real-time process monitoring and control to ensure consistent and reliable part dimensional accuracy. This research shows that support vector regression (SVR) and convolutional neural network (CNN) models offer a promising solution for real-time process control due to the models’ abilities to recognize complex, non-linear patterns with high accuracy. A novel experiment was designed to compare the performance of SVR and CNN models to indirectly detect bead height from a coaxial image of a melt pool from a single-layer, single bead build. The study showed that both SVR and CNN models trained on melt pool data collected from a coaxial optical camera can accurately predict the bead height with a mean absolute percentage error of 3.67% and 3.68%, respectively.
Multi-Objective Aerodynamic and Aeroelastic Coupled Design Optimization Using a Full Viscosity Discrete Adjoint Harmonic Balance Method
Authors: Wu Hangkong , Wang Dingxi , Huang Xiuquan
Published: June 2023

With increasing requirements for high-loading and high-efficiency turbomachines, blades become thinner and thinner and thus design optimizations considering both aerodynamic performances and aeroelastic stability become more and more necessary. In this study, a full viscosity discrete adjoint harmonic balance solver has been developed using algorithmic differentiation (AD), verified by a discrete linear solver based upon duality property, and then adopted to perform multi-disciplinary coupled design optimizations. To this end, a framework of multi-objective adjoint design optimizations has been developed to improve both aerodynamic performances and the aeroelastic stability of turbomachinery blades. This framework is divided into two steps: aeroelastic design initialization and aerodynamic Pareto front determination. First, the blade profiles are optimized to improve the aeroelastic stability only and constrain the variations of aerodynamic performances. Second, the optimized blade profiles in the first step are used as the initial ones and then further optimized with the objective function of aerodynamic parameters and the constraints of aeroelastic parameters. The effectiveness of the multi-objective design optimization method is demonstrated by comparing the optimization results with those from a single-objective aerodynamic and aeroelastic coupled design optimization method. The results from the transonic NASA Rotor 67 subjected to a hypothetical vibration mode show that the multi-objective coupled design optimization method is capable of improving performances in both disciplines.
Fan Flutter Mechanisms Related to Blade Mode Shape and Acoustic Properties
Authors: Dong Xu , Zhang Yanfeng , Lu Xingen
Published: June 2023

The blade mode shape and acoustic properties are important factors that affect the aeroelasticity of fan blades. The goal of this paper is to investigate the stall flutter mechanism associated with the first mode and its components. The paper numerically studies the impact of blade modes on fan flutter under different acoustic propagation conditions. The research focus includes unsteady characteristics inside blade passages, variations in pressure waves under different acoustic modes, as well as the effects of blade modes on the least stable phase angle. The results show that the twist-induced pressure leads to destabilization. Compared with the work of other authors, this study discovered that when the twist-induced pressure on the pressure side act on the plunge rather than twist, the instability effect will be greater, while the effect of twist-induced pressure on the suction side is weak. The phase of unsteady pressure in two-dimensional flow regions is linear with frequency, while the amplitude is highly sensitive to acoustic properties. The plunge-induced pressure inside the passage undergoes significant changes when downstream from acoustic cut-off to cut-on. The twist-induced pressure is more sensitive to changes in the acoustic propagation state, with the peak of the aerodynamic damping curve near upstream acoustic resonance being solely related to the twist-induced pressure acting on the suction side. The study also finds that the position of the blade torsion axis, represented by the twist-to-plunge ratio, does not affect the most unstable nodal diameter.
Taxonomic contribution to the knowledge of the subgenus Scheloribates (Topobates) (Acari, Oribatida, Scheloribatidae), with description of a new species from China
Authors: Xu Shu-Jing , Chen Jun
Published: June 2023

Species from China of the subgenus Scheloribates (Topobates) are studied, with description of a new species Scheloribates (Topobates) tibetensis sp. nov. based on adult specimens from Tibet. The new species differs from S. (T.) lanceolatus Wallwork, 1977 by heterotridactylous (versus monodactylous), shorter interlamellar seta, not forward to the tip of rostrum (versus longer interlamellar seta, beyond forward to the tip of the rostrum), genital seta g1 longer than g2–g4 (versus genital seta g1 similar to g2–g4 in length). A key to known species of Scheloribates (Topobates) is provided.
The Effectiveness of Advanced Cardiac Testing on Identifying Risk for Sudden Cardiac Arrest/Death in Athletes Following COVID-19 Infection During Preparticipation Examination: A Critically Appraised Topic
Authors: Wysmierski Sydney , Hall Emily A. , Garofalo Greg , Lopez Rebecca
Published: June 2023

Clinical Scenario: Due to the potential side effects in athletes, there is a need to evaluate for cardiac-related side effects due to COVID-19 infection during preparticipation examinations. Clinical Question: Does advanced cardiac testing during preparticipation examinations in athletes who have contracted the COVID-19 virus identify cardiac abnormalities? Summary of Key Findings: The literature was searched based on athletes’ post–COVID-19 infection who were tested for risk of sudden cardiac arrest/death. The initial search yielded 32 studies, but 7 were excluded based on abstract content. Of the remaining 25 studies, 17 were excluded based on patient age or non-athletic populations. Four relevant studies met the inclusion criteria and were included. The need for cardiac screening and advanced cardiac testing was supported to identify risk of sudden cardiac arrest/death during preparticipation examinations in COVID-19–positive patients. Clinical Bottom Line: The use of advanced cardiac testing along with a comprehensive symptom and history questionnaire is essential to reduce cardiac complications due to COVID-19. Symptom-based questionnaires following COVID-19 infection can detect possible COVID-19–related cardiac abnormalities better than the standard cardiac symptom-based questionnaires alone. These combined screening measures for patients with a COVID-19 infection can safely help return athletes to sports. Strength of Recommendation: This recommendation has a strength of B based on Oxford Centre for Evidence-Based Medicine due to consistently lower quality limited evidence that supports the use of advanced cardiac testing in identifying heart-related complications and risk of sudden cardiac arrest/death in COVID-19–positive patients.
Transcranial Direct Current Stimulation for Improving Outcomes in Patients With Chronic Ankle Instability: A Critically Appraised Paper
Authors: Majewski-Schrage Tricia L. , Snyder Kelli R.
Published: June 2023

Focused Clinical Question: Is there evidence to suggest that transcranial direct current stimulation improves clinical and patient-reported outcomes in patients with chronic ankle instability? Clinical Bottom Line: Evidence from two clinical studies supports the use of transcranial direct current stimulation for improving outcomes in patients with chronic ankle instability.
Running Habits and Injury Frequency Following COVID-19 Restrictions in Adolescent Long-Distance Runners
Authors: Meyers Rachel N. , Garcia Micah C. , Taylor-Haas Jeffery A. , Long Jason T. , Rauh Mitchell J. , Paterno Mark V. , Ford Kevin R. , Bazett-Jones David M.
Published: June 2023

Purpose: A decline in youth running was observed at the start of the COVID-19 pandemic. We investigated whether the resumption of organized running after social distancing restrictions changed running habits or injury frequency in adolescent runners. Methods: Adolescents (age = 16.1 [2.1] y) who participated in long-distance running activities completed an online survey in the Spring and Fall of 2020. Participants self-reported average weekly running habits and whether they sustained an injury during the Fall 2020 season. Poisson regression models and 1-way analysis of variance compared running habits while Fisher exact test compared differences in frequencies of injuries during Fall 2020 among season statuses (full, delayed, and canceled). Results: All runners, regardless of season status, increased weekly distance during Fall 2020. Only runners with a full Fall 2020 season ran more times per week and more high-intensity runs per week compared with their Spring 2020 running habits. There were no differences in running volume or running-related injury frequency among Fall 2020 season statuses. Conclusions: There were no significant differences in running-related injury (RRI) frequency among runners, regardless of season status, following the resumption of cross-country. Health care providers may need to prepare for runners to increase running volume and intensity following the resumption of organized team activities.
Unique evolution of foraminiferal calcification to survive global changes
Authors: Ujiié Yurika , Ishitani Yoshiyuki , Nagai Yukiko , Takaki Yoshihiro , Toyofuku Takashi , Ishii Shun’ichi
Published: June 2023

Foraminifera, the most ancient known calcium carbonate–producing eukaryotes, are crucial players in global biogeochemical cycles and well-used environmental indicators in biogeosciences. However, little is known about their calcification mechanisms. This impedes understanding the organismal responses to ocean acidification, which alters marine calcium carbonate production, potentially leading to biogeochemical cycle changes. We conducted comparative single-cell transcriptomics and fluorescent microscopy and identified calcium ion (Ca
2+
) transport/secretion genes and α-carbonic anhydrases that control calcification in a foraminifer. They actively take up Ca
2+
to boost mitochondrial adenosine triphosphate synthesis during calcification but need to pump excess intracellular Ca
2+
to the calcification site to prevent cell death. Unique α-carbonic anhydrase genes induce the generation of bicarbonate and proton from multiple CO
2
sources. These control mechanisms have evolved independently since the Precambrian to enable the development of large cells and calcification despite decreasing Ca
2+
concentrations and pH in seawater. The present findings provide previously unknown insights into the calcification mechanisms and their subsequent function in enduring ocean acidification.
Observation of natural flexural pulse waves in retinal and carotid arteries for wall elasticity estimation
Authors: Laloy-Borgna Gabrielle , Puyo Léo , Nishino Hidero , Atlan Michael , Catheline Stefan
Published: June 2023

The risk of cardiovascular events is linked to arterial elasticity that can be estimated from the pulse wave velocity. This symmetric wave velocity is related to the wall elasticity through the Moens-Korteweg equation. However, ultrasound imaging techniques need improved accuracy, and optical measurements on retinal arteries produce inconsistent results. Here, we report the first observation of an antisymmetric pulse wave: the flexural pulse wave. An optical system performs in vivo wave velocity measurements on retinal arteries and veins. Velocity estimation ranges between 1 and 10 millimeter per second. The theory of guided waves confirms the existence of this wave mode and its low velocity. Natural flexural waves can also be detected at the bigger scale of a carotid artery using ultrafast ultrasound imaging. This second natural pulse wave has great potential of becoming a biomarker of blood vessel aging.
Small reductions in cargo vessel speed substantially reduce noise impacts to marine mammals
Authors: Findlay Charlotte R. , Rojano-Doñate Laia , Tougaard Jakob , Johnson Mark P. , Madsen Peter Teglberg
Published: June 2023

Global reductions in the underwater radiated noise levels from cargo vessels are needed to reduce increasing cumulative impacts to marine wildlife. We use a vessel exposure simulation model to examine how reducing vessel source levels through slowdowns and technological modifications can lessen impacts on marine mammals. We show that the area exposed to ship noise reduces markedly with moderate source-level reductions that can be readily achieved with small reductions in speed. Moreover, slowdowns reduce all impacts to marine mammals despite the longer time that a slower vessel takes to pass an animal. We conclude that cumulative noise impacts from the global fleet can be reduced immediately by slowdowns. This solution requires no modification to ships and is scalable from local speed reductions in sensitive areas to ocean basins. Speed reductions can be supplemented by routing vessels away from critical habitats and by technological modifications to reduce vessel noise.
Thin film design of amorphous hafnium oxide nanocomposites enabling strong interfacial resistive switching uniformity
Authors: Hellenbrand Markus , Bakhit Babak , Dou Hongyi , Xiao Ming , Hill Megan O. , Sun Zhuotong , Mehonic Adnan , Chen Aiping , Jia Quanxi , Wang Haiyan , MacManus-Driscoll Judith L.
Published: June 2023

A design concept of phase-separated amorphous nanocomposite thin films is presented that realizes interfacial resistive switching (RS) in hafnium-oxide-based devices. The films are formed by incorporating an average of 7% Ba into hafnium oxide during pulsed laser deposition at temperatures ≤400°C. The added Ba prevents the films from crystallizing and leads to ∼20-nm-thin films consisting of an amorphous HfOxhost matrix interspersed with ∼2-nm-wide, ∼5-to-10-nm-pitch Ba-rich amorphous nanocolumns penetrating approximately two-thirds through the films. This restricts the RS to an interfacial Schottky-like energy barrier whose magnitude is tuned by ionic migration under an applied electric field. Resulting devices achieve stable cycle-to-cycle, device-to-device, and sample-to-sample reproducibility with a measured switching endurance of ≥104cycles for a memory window ≥10 at switching voltages of ±2 V. Each device can be set to multiple intermediate resistance states, which enables synaptic spike-timing–dependent plasticity. The presented concept unlocks additional design variables for RS devices.
Boosting internal quantum efficiency via ultrafast triplet transfer to 2H-MoTe
2
film
Authors: Jang Yu Jin , Paul Kamal Kumar , Park Jin Cheol , Kim Meeree , Tran Minh Dao , Song Hyun Yong , Yun Seok Joon , Lee Hyoyoung , Enkhbat Temujin , Kim JunHo , Lee Young Hee , Kim Ji-Hee
Published: June 2023

Organic systems often allow to create two triplet spin states (triplet excitons) by converting an initially excited singlet spin state (a singlet exciton). An ideally designed organic/inorganic heterostructure could reach the photovoltaic energy harvest over the Shockley-Queisser (S-Q) limit because of the efficient conversion of triplet excitons into charge carriers. Here, we demonstrate the molybdenum ditelluride (MoTe
2
)/pentacene heterostructure to boost the carrier density via efficient triplet transfer from pentacene to MoTe
2
using ultrafast transient absorption spectroscopy. We observe carrier multiplication by nearly four times by doubling carriers in MoTe
2
via the inverse Auger process and subsequently doubling carriers via triplet extraction from pentacene. We also verify efficient energy conversion by doubling the photocurrent in the MoTe
2
/pentacene film. This puts a step forward to enhancing photovoltaic conversion efficiency beyond the S-Q limit in the organic/inorganic heterostructures.
Unexpected bending behavior of architected 2D lattice materials
Authors: Yao Yu , Ni Yong , He Linghui
Published: June 2023

Architected two-dimensional (2D) lattice materials consisting of elastic beams are appealing because of their tunable sign of Poisson’s ratio. A common belief is that such materials with positive and negative Poisson’s ratios display anticlastic and synclastic curvatures, respectively, when bent in one direction. Here, we show theoretically and demonstrate experimentally that this is not true. For 2D lattices with star-shaped unit cells, we find a transition between anticlastic and synclastic bending curvatures controlled by the beam’s cross-sectional aspect ratio even at a fixed Poisson’s ratio. The mechanisms lay in the competitive interaction between axial torsion and out-of-plane bending of the beams and can be well captured by a Cosserat continuum model. Our result may provide unprecedented insights to the design of 2D lattice systems for shape-shifting applications.
An ultrasound-activatable platinum prodrug for sono-sensitized chemotherapy
Authors: Liu Gongyuan , Zhang Yachao , Yao Houzong , Deng Zhiqin , Chen Shu , Wang Yue , Peng Wang , Sun Guohan , Tse Man-Kit , Chen Xianfeng , Yue Jianbo , Peng Yung-Kang , Wang Lidai , Zhu Guangyu
Published: June 2023

Despite the great success achieved by photoactivated chemotherapy, eradicating deep tumors using external sources with high tissue penetration depth remains a challenge. Here, we present cyaninplatin, a paradigm of Pt(IV) anticancer prodrug that can be activated by ultrasound in a precise and spatiotemporally controllable manner. Upon sono-activation, mitochondria-accumulated cyaninplatin exhibits strengthened mitochondrial DNA damage and cell killing efficiency, and the prodrug overcomes drug resistance as a consequence of combined effects from released Pt(II) chemotherapeutics, the depletion of intracellular reductants, and the burst of reactive oxygen species, which gives rise to a therapeutic approach, namely sono-sensitized chemotherapy (SSCT). Guided by high-resolution ultrasound, optical, and photoacoustic imaging modalities, cyaninplatin realizes the overall theranostics of tumors in vivo with superior efficacy and biosafety. This work highlights the practical utility of ultrasound to precisely activate Pt(IV) anticancer prodrugs for the eradication of deep tumor lesions and broadens the biomedical uses of Pt coordination complexes.
Speciation atlas of polyoxometalates in aqueous solutions
Authors: Gumerova Nadiia I. , Rompel Annette
Published: June 2023

Speciation is the key parameter in solution chemistry that describes the composition, concentration, and oxidation state of each chemical form of an element present in a sample. The speciation study of complex polyatomic ions has remained challenging because of the large number of factors affecting stability and the limited number of direct methods. To address these challenges, we developed the speciation atlas of 10 polyoxometalates commonly used in catalytic and biological applications in aqueous solutions, where the speciation atlas provides both a species distribution database and a predictive model for other polyoxometalates to be used. Compiled for six different polyoxometalate archetypes with three types of addenda ions based on 1309 nuclear magnetic resonance spectra under 54 different conditions, the atlas has revealed a previously unknown behavior of polyoxometalates that may account for their potency as biological agents and catalysts. The atlas is intended to promote the interdisciplinary use of metal oxides in various scientific fields.
The future of whales in our Anthropocene ocean
Authors: McCauley Douglas J.
Published: June 2023

Slowing down ships presents one of several promising avenues for reducing harm to whales in an increasingly noisy and busy ocean.
An improved reporter identifies ruxolitinib as a potent and cardioprotective CaMKII inhibitor
Authors: Reyes Gaido Oscar E. , Pavlaki Nikoleta , Granger Jonathan M. , Mesubi Olurotimi O. , Liu Bian , Lin Brian L. , Long Alan , Walker David , Mayourian Joshua , Schole Kate L. , Terrillion Chantelle E. , Nkashama Lubika J. , Hulsurkar Mohit M. , Dorn Lauren E. , Ferrero Kimberly M. , Huganir Richard L. , Müller Frank U. , Wehrens Xander H. T. , Liu Jun O. , Luczak Elizabeth D. , Bezzerides Vassilios J. , Anderson Mark E.
Published: June 2023

Ca
2+
/calmodulin-dependent protein kinase II (CaMKII) hyperactivity causes cardiac arrhythmias, a major source of morbidity and mortality worldwide. Despite proven benefits of CaMKII inhibition in numerous preclinical models of heart disease, translation of CaMKII antagonists into humans has been stymied by low potency, toxicity, and an enduring concern for adverse effects on cognition due to an established role of CaMKII in learning and memory. To address these challenges, we asked whether any clinically approved drugs, developed for other purposes, were potent CaMKII inhibitors. For this, we engineered an improved fluorescent reporter, CaMKAR (CaMKII activity reporter), which features superior sensitivity, kinetics, and tractability for high-throughput screening. Using this tool, we carried out a drug repurposing screen (4475 compounds in clinical use) in human cells expressing constitutively active CaMKII. This yielded five previously unrecognized CaMKII inhibitors with clinically relevant potency: ruxolitinib, baricitinib, silmitasertib, crenolanib, and abemaciclib. We found that ruxolitinib, an orally bioavailable and U.S. Food and Drug Administration–approved medication, inhibited CaMKII in cultured cardiomyocytes and in mice. Ruxolitinib abolished arrhythmogenesis in mouse and patient-derived models of CaMKII-driven arrhythmias. A 10-min pretreatment in vivo was sufficient to prevent catecholaminergic polymorphic ventricular tachycardia, a congenital source of pediatric cardiac arrest, and rescue atrial fibrillation, the most common clinical arrhythmia. At cardioprotective doses, ruxolitinib-treated mice did not show any adverse effects in established cognitive assays. Our results support further clinical investigation of ruxolitinib as a potential treatment for cardiac indications.
BLM
overexpression as a predictive biomarker for CHK1 inhibitor response in PARP inhibitor–resistant
BRCA
-mutant ovarian cancer
Authors: Gupta Nitasha , Huang Tzu-Ting , Nair Jayakumar R. , An Daniel , Zurcher Grant , Lampert Erika J. , McCoy Ann , Cimino-Mathews Ashley , Swisher Elizabeth M. , Radke Marc R. , Lockwood Christina M. , Reichel Jonathan B. , Chiang Chih-Yuan , Wilson Kelli M. , Cheng Ken Chih-Chien , Nousome Darryl , Lee Jung-Min
Published: June 2023

Poly(ADP-ribose) polymerase inhibitors (PARPis) have changed the treatment paradigm in breast cancer gene (
BRCA
)–mutant high-grade serous ovarian carcinoma (HGSC). However, most patients eventually develop resistance to PARPis, highlighting an unmet need for improved therapeutic strategies. Using high-throughput drug screens, we identified ataxia telangiectasia and rad3-related protein/checkpoint kinase 1 (CHK1) pathway inhibitors as cytotoxic and further validated the activity of the CHK1 inhibitor (CHK1i) prexasertib in PARPi-sensitive and -resistant
BRCA
-mutant HGSC cells and xenograft mouse models. CHK1i monotherapy induced DNA damage, apoptosis, and tumor size reduction. We then conducted a phase 2 study (NCT02203513) of prexasertib in patients with
BRCA
-mutant HGSC. The treatment was well tolerated but yielded an objective response rate of 6% (1 of 17; one partial response) in patients with previous PARPi treatment. Exploratory biomarker analyses revealed that replication stress and fork stabilization were associated with clinical benefit to CHK1i. In particular, overexpression of Bloom syndrome RecQ helicase (
BLM
) and cyclin E1 (
CCNE1
) overexpression or copy number gain/amplification were seen in patients who derived durable benefit from CHK1i.
BRCA
reversion mutation in previously PARPi-treated
BRCA
-mutant patients was not associated with resistance to CHK1i. Our findings suggest that replication fork–related genes should be further evaluated as biomarkers for CHK1i sensitivity in patients with
BRCA
-mutant HGSC.
Complete Genomic Sequence of an Agarolytic
Pseudoalteromonas
Species Isolated from Deep Seawater
Authors: Muta Mikihisa , Yoshida Takao , Funatsu Takashi , Iizuka Ryo
Published: June 2023

We report the complete genomic sequence of the agarolytic bacterium
Pseudoalteromonas
sp. strain MM1, recovered from deep seawater. The genome has two circular chromosomes with sizes of 3,686,652 bp and 802,570 bp and GC contents of 40.8 and 40.0%, and it carries 3,967 protein-coding sequences, 24 rRNA genes, and 103 tRNA genes.
Genetic structure and triazole resistance among
Aspergillus fumigatus
populations from remote and undeveloped regions in Eastern Himalaya
Authors: Zhou Duanyong , Gong Jianchuan , Duan Chengyan , He Jingrui , Zhang Ying , Xu Jianping
Published: June 2023

Aspergillus fumigatus
is a ubiquitous mold and a common human fungal pathogen. Recent molecular population genetic and epidemiological analyses have revealed evidence for long-distance gene flow and high genetic diversity within most local populations of
A. fumigatus
. However, little is known about the impact of regional landscape factors in shaping the population diversity patterns of this species. Here we sampled extensively and investigated the population structure of
A. fumigatus
from soils in the Three Parallel Rivers (TPR) region in Eastern Himalaya. This region is remote, undeveloped and sparsely populated, bordered by glaciated peaks more than 6,000 m above sea level, and contained three rivers separated by tall mountains over very short horizontal distances. A total of 358
A
.
fumigatus
strains from 19 sites along the three rivers were isolated and analyzed at nine loci containing short tandem repeats. Our analyses revealed that mountain barriers, elevation differences, and drainage systems all contributed low but statistically significant genetic variations to the total
A. fumigatus
population in this region. We found abundant novel alleles and genotypes in the TPR population of
A. fumigatus
and significant genetic differentiation between this population and those from other parts of Yunnan and the globe. Surprisingly, despite limited human presence in this region, about 7% of the
A. fumigatus
isolates were resistant to at least one of the two medical triazoles commonly used for treating aspergillosis. Our results call for greater surveillance of this and other human fungal pathogens in the environment.

IMPORTANCE

The extreme habitat fragmentation and substantial environmental heterogeneity in the TPR region have long known to contribute to geographically shaped genetic structure and local adaptation in several plant and animal species. However, there have been limited studies of fungi in this region.
Aspergillus fumigatus
is a ubiquitous pathogen capable of long-distance dispersal and growth in diverse environments. In this study, using
A. fumigatus
as a model, we investigated how localized landscape features contribute to genetic variations in fungal populations. Our results revealed that elevation and drainage isolation rather than direct physical distances significantly impacted genetic exchange and diversity among the local
A. fumigatus
populations. Interestingly, within each local population, we found high allelic and genotypic diversities, and with evidence ~7% of all isolates being resistant to two medical triazoles, itraconazole and voriconazole. Given the high frequency of ARAF found in mostly natural soils of sparsely populated sites in the TPR region, close monitoring of their dynamics in nature and their effects on human health is needed.
Clinical and Molecular Characteristics and Antibacterial Strategies of Klebsiella pneumoniae in Pyogenic Infection
Authors: Yang Zhiyu , Zhou Runmei , Chen Yusheng , Zhang Xiaotuan , Liu Luogen , Luo Min , Chen Jinlin , Chen Kuilin , Zeng Tong , Liu Bin , Wu Yuan , Huang Jielite , Liu Zhuoran , Ouyang Jinglin
Published: June 2023

Klebsiella pneumoniae
may cause pyogenic infections, which are potentially life-threatening and bring great challenges for clinical management. However, the clinical and molecular characteristics of
K. pneumoniae
are poorly understood, and effective antibacterial treatment strategies are limited.
Mouse Liver-Expressed Shiftless Is an Evolutionarily Conserved Antiviral Effector Restricting Human and Murine Hepaciviruses
Authors: Zhang Yudi , Kinast Volker , Sheldon Julie , Frericks Nicola , Todt Daniel , Zimmer Matthias , Caliskan Neva , Brown Richard J. P. , Steinmann Eike , Pietschmann Thomas
Published: June 2023

Viruses have evolved ways to evade or blunt innate cellular antiviral mechanisms within their cognate host species. However, these adaptations may fail when viruses infect new species and can therefore limit cross-species transmission.
Reduced Susceptibility to Azoles in Cryptococcus gattii Correlates with the Substitution R258L in a Substrate Recognition Site of the Lanosterol 14-α-Demethylase
Authors: Carvajal Silvia Katherine , Melendres Javier , Escandón Patricia , Firacative Carolina
Published: June 2023

The fungal speciesCryptococcus neoformansandC. gattiiare human pathogens for which drug resistance or other treatment and management challenges exist. Here, we report differential susceptibility to azoles among both species, with some isolates displaying resistant phenotypes.
Associations of Circulating Estrogens and Estrogen Metabolites with Fecal and Oral Microbiome in Postmenopausal Women in the Ghana Breast Health Study
Authors: Wu Zeni , Pfeiffer Ruth M. , Byrd Doratha A. , Wan Yunhu , Ansong Daniel , Clegg-Lamptey Joe-Nat , Wiafe-Addai Beatrice , Edusei Lawrence , Adjei Ernest , Titiloye Nicholas , Dedey Florence , Aitpillah Francis , Oppong Joseph , Vanderpuye Verna , Osei-Bonsu Ernest , Dagnall Casey L. , Jones Kristine , Hutchinson Amy , Hicks Belynda D. , Ahearn Thomas U. , Knight Rob , Biritwum Richard , Yarney Joel , Wiafe Seth , Awuah Baffour , Nyarko Kofi , Garcia-Closas Montserrat , Sinha Rashmi , Figueroa Jonine D. , Brinton Louise A. , Trabert Britton , Vogtmann Emily
Published: June 2023

Several epidemiologic studies have found associations of urinary estrogens and estrogen metabolites with the fecal microbiome. However, urinary estrogen concentrations are not strongly correlated with serum estrogens, a known risk factor for breast cancer.
Interaction between Bombyx mori Cytoplasmic Polyhedrosis Virus NSP8 and BmAgo2 Inhibits RNA Interference and Enhances Virus Proliferation
Authors: Pan Jun , Qiu Qunnan , Kumar Dhiraj , Xu Jian , Tong Xinyu , Shen Zeen , Zhu Min , Hu Xiaolong , Gong Chengliang
Published: June 2023

It has been reported that the RNAi pathway is inhibited by binding RNAi suppressors encoded by some insect-specific viruses belonging toDicistroviridae,Nodaviridae, orBirnaviridaeto dsRNAs to protect dsRNAs from being cut by Dicer-2. However, it is unknown whether BmCPV, belonging toSpinareoviridae, encodes an RNAi suppressor.
Group B Streptococcus CRISPR1 Typing of Maternal, Fetal, and Neonatal Infectious Disease Isolates Highlights the Importance of CC1 in
In Utero
Fetal Death
Authors: Le Gallou Brice , Pastuszka Adeline , Lemaire Coralie , Mereghetti Laurent , Lanotte Philippe
Published: June 2023

Group B
Streptococcus
is the leading bacterium responsible for maternal and neonatal infections worldwide, also involved in preterm birth, stillbirth, and fetal death. In this study, we determined the clonal complex of all GBS isolates responsible for neonatal diseases (early- and late-onset diseases) and maternal invasive infections, including chorioamnionitis associated with
in utero
fetal death.
Black Carbon Seasonal Trends and Regional Sources on Bely Island (Arctic)
Authors: Popovicheva O. B. , Chichaeva M. A. , Kobelev V. O. , Kasimov N. S.
Published: June 2023

The impact of aerosol sources on the pollution of the Russian sector of the Arctic is now strongly underestimated. A new polar aerosol station was arranged in August 2019 on Bely Island (Kara Sea), on the pathway of air mass transport from industrial regions of Western Siberia to the Arctic. Continuous aethalometer measurements of a short-lived climate tracer, i.e., black carbon, (from December to April 2019 and from January to November 2020) showed its seasonal variations with high values (60–92 ng/m3) in December–April and low values (18–72 ng/m3) in June–September. Pollution periods are identified. Regional distribution of fossil fuel and biomass combustion sources are obtained using the black carbon concentration weight trajectory model. The impact of gas flaring from oil and gas extraction areas of Western Siberia, the Volga region, the Urals, and the Komi Republic is found to be most pronounced during the cold period, and the impact from wildfire smoke emissions is found to be maximal in the warm season. A marker of biomass burning impact, determined from the difference between the black carbon concentrations measured in a broad wavelength spectrum, indicated the predominant effects from residential wood combustion in the cold period and agricultural and forest fires in the warm season.
Developmental and behavioural outcomes at 2 years in babies born during the COVID-19 pandemic: communication concerns in a pandemic birth cohort
Authors: Byrne Susan , Sledge Hailey , Hurley Sadhbh , Hoolahan Sarah , Franklin Ruth , Jordan Norah , Boland Fiona , Murray Deirdre M , Hourihane Jonathan
Published: June 2023

Introduction

The CORAL (Impact of Corona Virus Pandemic on Allergic and Autoimmune Dysregulation in Infants Born During Lockdown) study reported a reduction in social communication milestones in 12-month-old infants born into the COVID-19 pandemic.

Aims

To look at 24-month developmental and behavioural outcomes in the CORAL cohort.

Design

The CORAL study is a longitudinal prospective observational study of Irish infants born in the first 3 months of the pandemic. At 24 months of age, the Ages and Stages Developmental Questionnaire (ASQ24) and the Child Behaviour Checklist (CBCL) were completed and compared with prepandemic BASELINE (Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Impact) cohort.

Results

917 babies (312 CORAL infants and 605 BASELINE infants) were included. At 24 months of age, infants in the CORAL and BASELINE cohorts had similar developmental ASQ24 scores in fine motor, problem solving and personal and social domains but ASQ24 communication scores were significantly lower in the CORAL group compared with the BASELINE cohort (mean (SD) 49.5 (15.1) vs 53.7 (11.6), p<0.01). Infants from the CORAL cohort were more likely to score below standardised cut-offs for developmental concern in the communication domain (11.9% CORAL compared with 5.4% BASELINE, p<0.01). Unadjusted ASQ24 gross motor scores were lower for the pandemic cohort. Fewer CORAL infants fell under 2 SD cut-off in personal-social subdomain. For CBCL, there was no evidence of difference in scores between the cohorts on multivariable analysis.

Conclusion

24-month-old pandemic-born infants had largely similar developmental and behavioural scores compared with their prepandemic counterparts. Concerns have been raised in the communication developmental domain.
PI3K/PTEN/mTOR pathway dynamic tracking and prognostic value in HR+/HER2− BC patients with residual disease after neoadjuvant chemotherapy: a cohort study
Authors: Miglietta Federica , Carraro Valentina , Amato Ottavia , Griguolo Gaia , Bottosso Michele , Munari Giada , Zarrilli Giovanni , Lo Mele Marcello , Barbieri Caterina , Dei Tos Angelo Paolo , Guarneri Valentina , Dieci Maria Vittoria , Fassan Matteo
Published: June 2023

Aims

Hormone receptor-positive (HR)+/HER2− breast cancer (BC) is highly heterogeneous, with PI3K/PTEN/mTOR pathway alterations emerging as possible players within this complexity. We longitudinally tracked PI3K/PTEN/mTOR pathway dynamics from baseline biopsy to residual disease (RD)—and to metastases in case of relapse—in HR+/HER2− BC patients receiving neoadjuvant chemotherapy (NACT).

Methods

HR+/HER2− BC patients with RD after NACT were identified. We assessedPIK3CAmutational, Pten-loss and phosphorylation levels of mTOR and its substrates (p70S6K and 4EBP1) on baseline biopsies and matched RD samples; in case of disease relapse, we also assessedPIK3CAmutational status on metastatic samples. Recurrence-free survival (RFS) was adopted as endpoint.

Results

92 patient were included. The conversion rate ofPIK3CAmutational status was 12.8%; 1 patient acquiredPIK3CAmutation at relapse; the rate of Pten conversion was 33.3%; mTOR phosphorylation levels significantly increased from baseline biopsy to RD, while its substrates significantly decreased. Baseline phosphorylated-mTOR significantly predicted poorer RFS in patients withPIK3CAwild-type status; baseline phosphorylated-70S6K was positively associated with RFS.

Conclusions

We observed that PI3K/PTEN/mTOR pathway is highly dynamic under NACT exposure and the assessment ofPIK3CAmutations may capture only a small fraction of such complexity. In this context, mTOR activation trough alternative pathways with respect toPIK3CAsignalling may have a crucial role in shaping the molecular landscape of HR+/HER2− BC with RD after NACT. It is imperative to further elucidate the role ofPIK3CAand mTOR-dependent pathways in shaping chemoresistance and endocrine resistance in high-risk HR+/HER2− early/locally advanced BC patients.