bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐intensity interval training improves cardiomyocyte contractile function and myofilament sensitivity to intracellular Ca2+ in obese rats
Authors: dos Santos Matheus Corteletti , da Silva Daniel Sesana , Cordeiro Jóctan Pimentel , Domingos Lucas Furtado , da Silva Gomes Ezio Henrique , Nogueira Breno Valentim , Bocalini Danilo Sales , Lima Leopoldo Ana Paula , Leopoldo André Soares
Published: August 2024

High‐intensity interval training (HIIT) has shown significant results in addressing adiposity and risk factors associated with obesity. However, there are no studies that investigate the effects of HIIT on contractility and intracellular Ca2+ handling. The purpose of this study was to explore the impact of HIIT on cardiomyocyte contractile function and intracellular Ca2+ handling in rats in which obesity was induced by a saturated high‐fat diet (HFD). Male Wistar rats were initially randomized into a standard diet and a HFD group. The experimental protocol spanned 23 weeks, comprising the induction and maintenance of obesity (15 weeks) followed by HIIT treatment (8 weeks). Performance was assessed using the maximum oxygen consumption test (). Evaluation encompassed cardiac, adipose and skeletal muscle histology, as well as contractility and intracellular Ca2+ handling. HIIT resulted in a reduction in visceral area, an increase in , and an augmentation of gastrocnemius fibre diameter in obese subjects. Additionally, HIIT led to a decrease in collagen fraction, an increase in percentage shortening, and a reduction in systolic Ca2+/percentage shortening and systolic Ca2+/maximum shortening rates. HIIT induces physiological cardiac remodelling, enhancing the contractile function of cardiomyocytes and improving myofilament sensitivity to Ca2+ in the context of obesity. This approach not only enhances cardiorespiratory and physical performance but also reduces visceral area and prevents interstitial fibrosis.
Simulation and Analysis of Solar-Assisted Air Source Heat Pump Heating System in Remote and Cold Regions
Authors: Tan Zilin , An Qier , Li Jingyang
Published: August 2024

In extremely cold and remote areas such as the west of the Inner Mongolia region, due to the vast land and sparse population, the coverage rate of heating pipes is low, resulting in high non-renewable energy consumption in building heating. To reduce the reliance on polluted energy and utilize sufficient solar energy resources, this study proposed a solar-assisted air source heat pump heating system (SASHP) and realized abundant heating supply for Taolai Airport Terminal in Ejina Banner. Indoor temperature during the heating season was simulated using the trnsys and the coldest month was selected for analyzing and evaluating the heating performance of the SASHP. Compared with a single air source heat pump heating system, the SASHP achieves a 45.81% reduction in energy consumption, and the system's energy efficiency ratio (SEER) increases from 4.14 to 7.85. In addition, the average indoor temperature is 1.02 °C higher than that of the traditional gas boiler heating system on the coldest day. Aiming to minimize the equivalent annual cost, Hooke–Jeeves algorithm is used to optimize key parameters of the SASHP and the solar fraction increased from 45.99% to 51.91%, the SEER improved from 7.85 to 8.74. The optimized system has significantly improved in terms of system performance, while also demonstrating good energy saving, environmental protection, and economic benefits, which can provide a reference for the optimization and application of similar projects.
Evaluating Fracture Energy Predictions Using Phase-Field and Gradient-Enhanced Damage Models for Elastomers
Authors: Mousavi S. Mohammad , Ang Ida , Mulderrig Jason , Bouklas Nikolaos
Published: August 2024

Recently, the phase-field method has been increasingly used for brittle fractures in soft materials like polymers, elastomers, and biological tissues. When considering finite deformations to account for the highly deformable nature of soft materials, the convergence of the phase-field method becomes challenging, especially in scenarios of unstable crack growth. To overcome these numerical difficulties, several approaches have been introduced, with artificial viscosity being the most widely utilized. This study investigates the energy release rate due to crack propagation in hyperelastic nearly-incompressible materials and compares the phase-field method and a novel gradient-enhanced damage (GED) approach. First, we simulate unstable loading scenarios using the phase-field method, which leads to convergence problems. To address these issues, we introduce artificial viscosity to stabilize the problem and analyze its impact on the energy release rate utilizing a domain J-integral approach giving quantitative measurements during crack propagation. It is observed that the measured energy released rate during crack propagation does not comply with the imposed critical energy release rate, and shows non-monotonic behavior. In the second part of the paper, we introduce a novel stretch-based GED model as an alternative to the phase-field method for modeling crack evolution in elastomers. It is demonstrated that in this method, the energy release rate can be obtained as an output of the simulation rather than as an input which could be useful in the exploration of rate-dependent responses, as one could directly impose chain-level criteria for damage initiation. We show that while this novel approach provides reasonable results for fracture simulations, it still suffers from some numerical issues that strain-based GED formulations are known to be susceptible to.
Offline Teaching Algorithm to Pass Through the Singularity for Robot Machining
Authors: Kato Daiki , Takeuchi Ayumu , Sekioka Masataka , Uchino Tomohiro , Nakagawa Masao , Hirogaki Toshiki , Aoyama Eiichi
Published: August 2024

This study proposes an algorithm to change the type of inverse kinematics solution for a 6-Degrees of Freedom (DOF) manipulator to pass through the vicinity of a singularity, where the inverse kinematics solution is not determined. Some joints rotate rapidly when passing through the singularity and its vicinity. A general 6-DOF manipulator has eight different inverse kinematics solutions. The proposed algorithm suppressed the rapid rotation by changing the type of inverse kinematics solution when passing through the singularity. However, in the vicinity of the singularity, the joint rotates rapidly because of the connection between different types of discontinuous solutions. Therefore, we defined an interpolation area in the vicinity of the singularity where the rotational speed of the joint is k (0 < k ≦ 1) times or more than the maximum rotational speed of the servomotor and linearly interpolated the joint angles. This algorithm generated a pitch angle error, which was used to determine whether solution type for each Tool Center Point (TCP) speed was to be changed or maintained. The algorithm was verified on a large industrial robot with a 6-DOF manipulator. The rapid rotation of joints passing through the vicinity of the singularity was suppressed depending on the TCP speed and distance from the singularity.
Real-Time Recovery From Cyberattacks on Manufacturing Processes
Authors: Mangrolia Brijesh , Cleeman Jeremy , Patel Anandkumar , Jackson Adrian , Malhotra Rajiv
Published: August 2024

Material integrity cyberphysical attacks induce defects in parts that compromise their functionality. The socio-economic cost of monitoring-based part disposal and production stoppage necessitates rapid in-process recovery from continued defect formation. But cyberattacks can circumvent existing real-time control by introducing intermittent and a-priori unknown perturbations of exogenous process parameters. This paper presents a novel AI-based framework to address this issue and examines its capabilities for Fused Filament Fabrication (FFF) as an example. We demonstrate real-time recovery from inter-road defects created by attacks on endogenous and exogenous parameters, both trained- and untrained-for, with unprecedented spatial resolution.
Automated NC Program Generation for Complex Shapes With 5-Axis Indexing Machining
Authors: Matsukawa Kentaro , Nakatsuji Hidenori , Nishida Isamu
Published: August 2024

In recent years, the manufacturing industry has encountered a surge in demand for high-mix, low-volume production alongside a shortage of human resources. Accordingly, there is an increasing demand for 5-axis machining centers that can efficiently and accurately machine parts and products with complex geometries. Machining three-dimensional shapes, including complex curved surfaces, typically uses simultaneous 5-axis machining. However, it is difficult for 5-axis machining to create numerically controlled (NC) programs. This study developed a system that automatically generates NC programs for machining complex shapes by 5-axis indexing using only a computer-aided design (CAD) model of the product in standard triangulated language (STL) format as input information and demonstrated the effectiveness of this system.
Production Planning Algorithm for a Pre-Cut Lumber Factory Using Metaheuristics
Authors: Tanizaki Takashi , Arino Masahide , Kataoka Takayuki
Published: August 2024

In Japan, the demand for wooden houses is increasing while the number of carpenters is decreasing. Therefore, it is necessary to improve productivity in wooden house construction. This has led to an increase in the use of the pre-cut method. The pre-cut method is a method in which raw materials (base woods) and joints are processed in advance based on the design. Compared to conventional methods, the pre-cut method has various advantages, such as reduced construction time at the construction site and improved processing accuracy. With the above background, we have been conducting to improve the efficiency of pre-cut lumber production factories to increase productivity in wooden construction. After processing, pre-cut lumber is packed according to a pre-determined packaging sequence to improve work efficiency at the building site. When pre-cut lumbers that do not match the packaging sequence are produced, they are temporarily stored in a space. To reduce space and production time in a pre-cut lumber production factory, we studied a practical production planning algorithm using metaheuristics that minimizes the maximum number of racks used with pre-cut lumber production company A and confirmed the effectiveness of the proposed algorithm through numerical experiments.
Investigation of Tooth Meshing of Natural Fiber Bevel Gears Composed of Only Bamboo Fibers Extracted Using a Machining Center
Authors: Nakaya Soichiro , Tanaka Kaito , Nakagawa Masao , Hirogaki Toshiki , Aoyama Eichi , Nobe Hiromichi
Published: August 2024

The primary gears currently used are composed of metal and plastic. Therefore, new gears that can overcome the disadvantages of these two types of gears while maintaining their advantages must be developed. Sustainable and reproducible natural materials have been developed to address these environmental issues. Bamboo is abundantly found in Japan, and has a low environmental impact owing to its quick growth. Bamboo fibers have a high specific strength and stiffness, and their light weight renders them as promising materials for several applications. In a previous study, bamboo fibers were extracted with high quality and precision via end-milling using a machining center, and spur gears were successfully produced via self-adhesion using a hot-press machine. In this study, bevel gears molded using only bamboo fibers in molds were used as experimental subjects. The meshing conditions were investigated by measuring the tooth root strain and load torque during driving.
Synchronous Averaging Preprocessing of Gearbox Vibration Signals: A Comparison of Classification Performance
Authors: Javadian David , Diehl Edward , Tang Jiong
Published: August 2024

A classical method of determining the condition of a gearbox has been the analysis of vibration signals. The characteristics of a vibration signal captured from a gearbox are heavily dependent on systems parameters such as the speed profile and meshing harmonics as well as variations from a variety of sources. One means by which the influence of these parameters can be minimized is through synchronous averaging techniques. However, different synchronous averaging techniques return different signal outputs, and the ability to extract useful information regarding the condition of a gearbox thus varies as well. This research seeks to objectively compare the strengths and weaknesses of two synchronous averaging techniques with respect to gearbox condition classification performance. By using a numerical model, vibration signals from an idealized gearbox with known defects and uncertainties are generated with both a constant speed and varying speed. These signals are then processed using time-synchronous averaging and angle-frequency domain synchronous averaging, respectively, to return feature enriched signal data. Both sets of synchronously averaged data are then processed through a simple, general benchmark convolutional neural network to predict the condition of the gearbox. The classification performance and consistency returned highlights the strengths of synchronous averaging as a preprocessing step for gearbox classification.
Integrating Mediapipe Module for Learn From Demonstration on Cobots
Authors: Syed Ishaq Shahzad , Matheswaran Keerthivaasan , Li Cheryl Q.
Published: August 2024

This paper introduces an innovative framework for Learn from Demonstration applied to collaborative robots, leveraging the advantages of Mediapipe, a computer vision tool in conjunction with a camera system. Given the collaborative nature, robots of this type are well-suited for human-robot interaction scenarios, and our proposed approach enhances their adaptability and learning capabilities through visual demonstration. Within the Robot Operating System environment, the collaborative robot equipped with a camera system serves as a standardized platform for control and communication. The integration of Mediapipe enhances the system’s visual perception and comprehension, empowering it with robust capabilities for Learning from Demonstration. This research extends the realm of collaborative robotics by introducing a unified framework that capitalizes on the synergies among Mediapipe, Robot Operating System, camera systems, and cobots. The proposed method shows potential for applications demanding flexible and intuitive human-robot cooperation in real-world scenarios.
The fungal natural product fusidic acid demonstrates potent activity against
Mycoplasma genitalium
Authors: Wood Gwendolyn E. , Lee Jin Woo , Peramuna Thilini , Wendt Karen L. , Kim Caroline M. , Aguila Laarni Kendra T. , Calderon Claire L. , Cichewicz Robert H.
Published: August 2024

Antimicrobial resistance is extremely common in
Mycoplasma genitalium
, a frequent cause of urethritis in men and cervicitis, vaginitis, and pelvic inflammatory disease in women. Treatment of
M. genitalium
infections is difficult due to intrinsic and acquired resistance to many antibiotic classes. We undertook a program to identify novel antimicrobials with activity against
M. genitalium
from fungal natural products. Extracts of
Ramularia coccinea
contained a molecule with potent activity that was subsequently identified as fusidic acid, a fusidane-type antibiotic that has been in clinical use for decades outside the United States. We found that minimum inhibitory concentrations of fusidic acid ranged from 0.31 to 4 µg/mL among 17
M
.
genitalium
strains including laboratory-passaged and low-passage clinical isolates. Time-kill data indicate that bactericidal killing occurs when
M. genitalium
is exposed to ≥10 µg/mL for 48 h, comparing favorably to serum concentrations obtained from typical loading dose regimens. Resistance to fusidic acid was associated with mutations in
fusA
consistent with the known mechanism of action in which fusidic acid inhibits protein synthesis by binding to elongation factor G. Interestingly, no mutants resistant to >10 µg/mL fusidic acid were obtained and a resistant strain containing a F435Y mutation in FusA was impaired for growth
in vitro
. These data suggest that fusidic acid may be a promising option for the treatment of
M. genitalium
infections.
Host-pathogen associations inferred from bloodmeal analyses of
Ixodes scapularis
ticks in a low biodiversity setting
Authors: Tufts Danielle M. , Goethert Heidi K. , Diuk-Wasser Maria A.
Published: August 2024

Tick-borne pathogen emergence is dependent on the abundance and distribution of competent hosts in the environment.
Ixodes scapularis
ticks are generalist feeders, and their pathogen infection prevalence depends on their relative feeding on local competent and non-competent hosts. The ability to determine what host a larval life stage tick fed on can help predict infection prevalence, emergence, and spread of certain tick-borne pathogens and the risks posed to public health. Here, we use a newly developed genomic target-based technique to detect the source of larval bloodmeals by sampling questing nymphs from Block Island, RI, a small island with a depauperate mammalian community. We used previously designed specific assays to target all known hosts on this island and analyzed ticks for four human pathogenic tick-borne pathogens. We determined the highest proportion of larvae fed on avian species (42.34%), white-footed mice (36.94%), and white-tailed deer (20.72%) and occasionally fed on feral cats, rats, and voles, which are in low abundance on Block Island. Additionally, larvae that had fed on white-footed mice were significantly more likely to be infected with
Borrelia burgdorferi
and
Babesia microti,
while larvae that had fed on white-footed mice or white-tailed deer were significantly more likely to be infected with, respectively, mouse- and deer-associated genotypes of
Anaplasma phagocytophilum
. The ability to detect a nymph’s larval host allows for a better understanding of tick feeding behavior, host distribution, pathogen prevalence, and zoonotic risks to humans, which can contribute to better tick management strategies.

IMPORTANCE

Tick-borne diseases, such as Lyme disease, babesiosis, and anaplasmosis, pose significant public health burdens. Tick bloodmeal analysis provides a noninvasive sampling method to evaluate tick-host associations and combined with a zoonotic pathogen assay, can generate crucial insights into the epidemiology and transmission of tick-borne diseases by identifying potential key maintenance hosts. We investigated the bloodmeals of questing
Ixodes scapularis
nymphs. We found that avian hosts, white-footed mice, and white-tailed deer fed the majority of larval ticks and differentially contributed to the prevalence of multiple tick-borne pathogens and pathogen genotypes in a low biodiversity island setting. Unraveling the intricate network of host-vector-pathogen interactions will contribute to improving wildlife management and conservation efforts, to developing targeted surveillance, and vector and host control efforts, ultimately reducing the incidence of tick-borne diseases and improving public health.
Regulation of the cell surface expression of classical and non-classical MHC proteins by the human cytomegalovirus UL40 and rhesus cytomegalovirus Rh67 proteins
Authors: Brackenridge Simon , John Nessy , He Wanlin , Früh Klaus , Borrow Persephone , McMichael Andrew
Published: August 2024

The signal sequences of the human cytomegalovirus (CMV) UL40 protein and its rhesus CMV (RhCMV) counterpart, Rh67, contain a peptide (VMAPRT[L/V][F/I/L/V]L, VL9) that is presented by major histocompatibility complex (MHC) antigen E (MHC-E). The CMV VL9 peptides replace VL9 peptides derived from classical MHC (Ia) signal sequences, which are lost when CMV disrupts antigen processing and presentation and MHC Ia expression. This allows infected cells to maintain MHC-E surface expression and escape killing by Natural Killer cells. We demonstrate that processing of the Rh67 VL9 peptide mirrors that of UL40, despite the lack of sequence conservation between the two proteins. Processing of both VL9 peptides is dependent on cleavage of their signal sequences by the host protease signal peptide peptidase. As previously shown for UL40, up-regulation of MHC-E expression by Rh67 requires only its signal sequence, with sequences upstream of VL9 critical for conferring independence from TAP, the transporter associated with antigen processing. Our results also suggest that the mature UL40 and Rh67 proteins contribute to CMV immune evasion by decreasing surface expression of MHC Ia. Unexpectedly, while the Rh67 VL9 peptide is resistant to the effects of Rh67, UL40 can partially counteract the up-regulation of MHC-E expression mediated by its own VL9 peptide. This suggests differences in the mechanisms by which the two VL9 peptides up-regulate MHC-E, and further work will be required to determine if any such differences have implications for translating a RhCMV-vectored simian immunodeficiency virus (SIV) vaccine to HIV-1 using human CMV as a vector.

IMPORTANCE

The protective immune response induced by a rhesus cytomegalovirus (RhCMV)-vectored simian immunodeficiency virus (SIV) vaccine in rhesus macaques depends on the presence of the viral Rh67 gene in the vaccine. The Rh67 protein contains a peptide that allows the RhCMV-infected cells to maintain expression of major histocompatibility complex (MHC) antigen E at the cell surface. We show that production of this peptide, referred to as “VL9,” mirrors that of the equivalent peptide present in the human cytomegalovirus (CMV) protein UL40, despite the little sequence similarity between the two CMV proteins. We also show that the mature UL40 and Rh67 proteins, which have no previously described function, also contribute to CMV immune evasion by reducing cell surface expression of MHC proteins important for the immune system to detect infected cells. Despite these similarities, our work also reveals possible differences between Rh67 and UL40, and these may have implications for the use of human CMV as the vector for a potential HIV-1 vaccine.
Draft genome of the caprolactam-degrading
Paenarthrobacter
sp. CAP02 isolated from a landfill
Authors: Rivera-Kohr David A. , Rodriguez-Ramos Damayanti , Tanner Lewis , Vo Phuong , Thalpur Neha A. , Nielsen-Fox Hans C. , Shatara Fuad J. , Bingman Craig A. , Hou Liyuan , Fox Brian G. , Majumder Erica L.-W.
Published: August 2024

Here, we report the draft genome sequence of
Paenarthrobacter
sp. CAP02, which metabolizes caprolactam as a sole source of carbon and nitrogen. This bacterium was isolated from Dane County Landfill Site No. 2 in Madison, WI, USA.
Supplemental Material: Early Cretaceous stress field variations and relationship to intraplate magmatism in the New England portion of the eastern North American margin
Authors: Boemmels J.R. Cooper , al. et
Published: August 2024

Text S1: Geochemical analysis methodology. Figures S1–S5: Field photographs with captions. Table S1: Geochemical analyses. Table S2: Fault-slip data. 
Augmented Cortisol and Antiglucocorticoid Therapy in Mood Disorders: the Hippocampus as a Potential Drug Target
Authors: Gulyaeva N. V.
Published: August 2024

The pathophysiology of many mood disorders is closely related
to abnormal stress response associated with the dysfunction of the
hypothalamic–pituitary–adrenal (HPA) axis and cortisol overproduction. The
hippocampus, a key structure of the limbic system responsible for
both cognitive and emotional spheres, is selectively vulnerable
to excess of glucocorticoids (GCs) inducing neuroinflammation and neurodegeneration.
The antiGC therapy of psychiatric diseases, in particular depressive
disorders, may be a useful additional treatment. Among other approaches,
targeting glucocorticoid receptors, abounded in the hippocampus,
is regarded as highly promising. However, though the preclinical
data provide fairly firm evidence to the concept of antiGC therapy
for stress-related diseases, clinical studies still are at the proof-of-concept
stage. Noteworthy, chronic GC excess is associated not only with
mood diseases, but also with cognitive decline, metabolic disorders,
diabetes. Potentially, antiGC (HPA axis modifying) therapy may alleviate
affective symptoms, cognitive disturbances, GC and insulin resistance
and adverse side effects of conventional drugs through beneficial
effects on the hippocampus mitigating its dysfunction and neurodegeneration,
neuroinflammation, and impairment of neurogenesis. Since stress/GC-associated
neuroinflammation-mediated pathology of the limbic system and, specifically,
the hippocampus, is a general feature typical for many brain diseases,
the concept of antiGC therapy may be extended, tested and validated
in a wider spectrum of cerebral pathologies.
Management of medically unexplained symptoms in children and young people: a secondary analysis of a 10-year audit of referrals to a Paediatric Psychology Service
Authors: Robinson Sally J , Colville Gillian A
Published: August 2024

This study evaluated service use of children and young people with medically unexplained symptoms (MUS) referred to a Paediatric Psychology Service between 2008 and 2017. Univariate analyses of activity data indicated that the MUS group (n=268) required more clinical sessions than other patients (n=3577) (inpatient MUS: 7.5 (12.5) vs general: 4.0 (6.0), p=0.006; outpatient: MUS 10.7 (15.0) vs general 6.3 (8.9), p<0.001). Multivariate analyses confirmed that MUS group status remained significantly associated (p<0.001) with a higher number of contacts, even when age and gender were controlled for. Although both groups benefitted equally from psychological input, MUS referrals required more contact time than general referrals.
Relationship between continuity of primary care and hospitalisation for patients with COPD: population-based cohort study from South Korea
Authors: Lee Iyn-Hyang , Choo Eunjung , Kim Sejung , Je Nam Kyung , Jo Ae Jeong , Jang Eun Jin
Published: August 2024

Objectives

The existing evidence for the impacts of continuity of care (COC) in patients with chronic obstructive pulmonary disease (COPD) is low to moderate. This study aimed to investigate the associations between relational COC within primary care and COPD-related hospitalisations using a robust methodology.

Design

Population-based cohort study.

Setting

National Health Insurance Service database, South Korea.

Participants

92 977 adults (≥40 years) with COPD newly diagnosed between 2015 and 2016 were included. The propensity score (PS) matching approach was used. PSs were calculated from a multivariable logistic regression that included eight baseline characteristics.

Exposure

COC within primary care.

Main outcome measures

The primary outcome was the incidence of COPD-related hospitalisations. Cox proportional hazard models were used to estimate HRs and 95% CIs.

Results

Out of 92 977 patients, 66 677 of whom were cared for continuously by primary doctors (the continuity group), while 26 300 were not (the non-continuity group). During a 4-year follow-up period, 2094 patients (2.25%) were hospitalised; 874 (1.31%) from the continuity group and 1220 (4.64%) from the non-continuity group. After adjusting for confounding covariates, patients in the non-continuity group exhibited a significantly higher risk of hospital admission (adjusted HR (aHR) 2.43 (95% CI 2.22 to 2.66)). This risk was marginally reduced to 2.21 (95% CI 1.99 to 2.46) after PS matching. The risk of emergency department (ED) visits, systemic corticosteroid use and costs were higher for patients in the non-continuity group (aHR 2.32 (95% CI 2.04 to 2.63), adjusted OR 1.25 (95% CI 1.19 to 1.31) and expβ=1.89 (95% CI 1.82 to 1.97), respectively). These findings remained consistent across the PS-matched cohort, as well as in the sensitivity and subgroup analyses.

Conclusions

In patients with COPD aged over 40, increased continuity of primary care was found to be associated with less hospitalisation, fewer ED visits and lower healthcare expenditure.
Local anaesthesia for pain control in surgical abortion before 14 weeks of pregnancy: a systematic review
Authors: Renner Regina , Ennis Madeleine , McKercher Adrienne , Henderson Jillian T , Edelman Alison
Published: August 2024

Background

Abortions are common and associated with procedural pain. We aimed to evaluate benefits and harms of local anaesthesia given for pain control during surgical abortion at less than 14 weeks' gestation.

Methods

We searched a systematic review on local anaesthesia for pain control for surgical abortion at less than 14 weeks' gestation using uterine aspiration. We searched multiple databases through December 2022. We evaluated study quality using the Cochrane Risk of Bias 2 (RoB2) instrument and assessed the certainty of evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Outcomes included intraoperative pain (with dilation, aspiration or procedure), patient satisfaction and adverse events.

Results

Thirteen studies with 1992 participants met the inclusion criteria and the majority were judged as low risk of bias. Intervention protocols were heterogeneous, limiting meta-analysis. A 20 mL 1% lidocaine paracervical block (PCB) reduced pain with dilation compared with sham PCB (mean difference (MD) −37.00, 95% CI −45.64 to −28.36) and aspiration (MD −26.00, 95% CI −33.48 to −18.52; 1 randomised controlled trial (RCT), n=120; high-certainty evidence). A PCB with 14 mL 1% chloroprocaine was associated with a slight reduction in pain during aspiration compared with normal saline PCB injected at two or four sites (MD −1.50, 95% CI −2.45 to −0.55; 1 RCT, n=79; high-certainty evidence). Other RCTs compared a range of local anaesthetic types, PCB techniques and topical anaesthetics. Participants reported moderately high satisfaction with any type of pain control and studies reported few adverse events that were rarely medication-related.

Conclusion

RCT evidence supports PCB efficacy but was inconsistent and of low certainty for topical anaesthesia.
Molecular biology as a driver in therapeutic choices for ovarian cancer
Authors: Arcieri Martina , Andreetta Claudia , Tius Veronica , Zapelloni Giulia , Titone Francesca , Restaino Stefano , Vizzielli Giuseppe
Published: August 2024

The majority of patients with ovarian cancer relapse within 3 years of first line chemotherapy. Therefore, choosing the most appropriate treatment in the recurrence setting has a fundamental role in defining a patient’s prognosis. Treatment options include systemic and intra-peritoneal chemotherapy, secondary cytoreductive surgery, and stereotactic body radiotherapy. The best therapeutic choice depends on multiple factors and not only on treatment-free interval. For systemic therapy, prior lines therapy, residual toxicities, comorbidities, performance status, and patient preferences should be taken into account. Secondary cytoreductive surgery can be proposed in patients in which complete tumor resectability can be predicted and in those with oligometastatic disease. Stereotactic body radiotherapy represents a valid alternative to surgery for oligometastatic disease with high local control and minimal toxicity. Current evidence has demonstrated an emerging role of BRCA mutational status and molecular profiling in the impacting response to systemic and local treatments. Therefore, these could provide guidance in the treatment decision process and help identify patients who respond better to poly(ADP-ribose) polymerase (PARP)-inhibitors or immunotherapy or to a combined approach with surgery rather than to platinum-based chemotherapy. Current knowledge in this field could help widen therapeutic options, especially for platinum-resistant patients. In this review, we offer an overview of the state of the art regarding the role of chemotherapy, radiotherapy, and surgery in this setting and their implications in clinical practice and in the treatment decision process, so as to provide the best tailored therapy in patients with recurrent ovarian cancer.
EWSR1: the promiscuous king of mesenchymal neoplasia
Authors: Towery Emily Anne , Papke David James
Published: August 2024

EWSR1is the most commonly rearranged gene in mesenchymal neoplasia, and its myriad chimeric oncoproteins drive widely disparate neoplasms. Here, we survey selectedEWSR1rearrangements, including well-describedEWSR1fusions with CREB family members,ATF1andCREB1, as well as fusions in emerging entities such as mesenchymal neoplasms withEWSR1::PATZ1andEWSR1::NFATC2fusions. We also discuss recent data demonstrating the imperfect specificity ofEWSR1::WT1and, possibly,EWSR1::FLI1fusions.
Inclusion, characteristics, and reporting of older adults in FDA registration studies of immunotherapy, 2018–2022
Authors: Mac Eochagain Colm , Power Robert , Sam Christine , Gonzalez-Senac Nicolas M , Walsh Darren , Roy Mukul , Battisti Nicolò Matteo Luca
Published: August 2024

Immune checkpoint inhibitors (ICI) have transformed the management of cancer, particularly for older adults, who constitute a majority of the global cancer patient population. This study aimed to assess the inclusion, characteristics, and reporting of older adults enrolled in Food and Drug Administration (FDA) registration clinical trials of ICI between 2018 and 2022. Clinical trials of ICI leading to an FDA approval in solid tumor oncology between 2018 and 2022 were included. Primary study reports and all available secondary publications were assessed. The availability and completeness of older subgroup data for protocol-defined clinical efficacy endpoints, health-related quality of life (HRQOL) and toxicity outcomes, and baseline characteristics were assessed according to predefined criteria which categorized reporting completeness hierarchically in relation to the availability of published data, including effect size, sample size, and measures of precision. 53 registration trials were included, involving a total of 37,094 participants. Most trials (64.2%) were of ICI combination therapy. 42.3% of patients were aged≥65 years; 11.1% were aged≥75. No trials specified an upper age limit for eligibility. 98.1% of trials excluded patients with European Cooperative Oncology Group performance status>1. 87.2% of primary efficacy endpoints and 17.9% of secondary efficacy endpoints were reported completely for older adults. Five studies (9.4%) reported baseline characteristics, three (6.1%) reported HRQOL assessments, and four (7.5%) reported toxicity outcomes completely among older subgroups. No trials conducted baseline geriatric assessments or reported geriatric-specific symptoms or quality of life scales. This analysis highlights significant deficits in the enrollment and reporting of older subgroups in pivotal trials of ICI therapy. The findings highlight an urgent need for improved reporting and inclusion standards in clinical trials of ICI to better inform treatment decisions for older adults.
Framing effects from misleading implicatures: an empirically based case against some purported nudges
Authors: Yeo Shang Long
Published: August 2024

Some bioethicists argue that a doctor may frame treatment options in terms of effects on survival rather than on mortality in order to influence patients to choose the better option. The debate over such framing typically assumes that the survival and mortality frames convey the same numerical information. However, certain empirical findings contest this numerical equivalence assumption, demonstrating that framing effects may in fact be due to the two frames implying different information about the numerical bounds of survival and mortality rates. In this paper, I use these findings to argue that framing is presumptively wrong because it violates the duty of proper disclosure. Along the way, I highlight morally relevant features affecting the permissibility of framing, tackle three objections and draw some general lessons for the ethics of nudging.
Loss-of-function variants in
JPH1
cause congenital myopathy with prominent facial and ocular involvement
Authors: Johari Mridul , Topf Ana , Folland Chiara , Duff Jennifer , Dofash Lein , Marti Pilar , Robertson Thomas , Vilchez Juan , Cairns Anita , Harris Elizabeth , Marini-Bettolo Chiara , Hundallah Khalid , Alhashem Amal M , Al-Owain Mohammed , Maroofian Reza , Ravenscroft Gianina , Straub Volker
Published: August 2024

Background

Weakness of facial, ocular and axial muscles is a common clinical presentation in congenital myopathies caused by pathogenic variants in genes encoding triad proteins. Abnormalities in triad structure and function resulting in disturbed excitation-contraction coupling and Ca
2+
homeostasis can contribute to disease pathology.

Methods

We analysed exome and genome sequencing data from four unrelated individuals with congenital myopathy characterised by facial, ocular and bulbar involvement. We collected deep phenotypic data from the affected individuals. We analysed the RNA-sequencing (RNA-seq) data of F3-II.1 and performed gene expression outlier analysis in 129 samples.

Results

The four probands had a remarkably similar clinical presentation with prominent facial, ocular and bulbar features. Disease onset was in the neonatal period with hypotonia, poor feeding, cleft palate and talipes. Muscle weakness was generalised but prominent in the lower limbs with facial weakness also present. All patients had myopathic facies, bilateral ptosis, ophthalmoplegia and fatigability. Muscle biopsy on light microscopy showed type 1 myofiber predominance and ultrastructural analysis revealed slightly reduced triads, and structurally abnormal sarcoplasmic reticulum.

DNA sequencing identified four unique homozygous loss-of-function variants in
JPH1
, encoding junctophilin-1 in the four families; one stop-gain (c.354C>A;p.Tyr118*) and three frameshift (c.373delG;p.Asp125Thrfs*30, c.1738delC;p.Leu580Trpfs*16 and c.1510delG;p. Glu504Serfs*3) variants. Muscle RNA-seq showed strong downregulation of
JPH1
in the F3 proband.

Conclusions

Junctophilin-1 is critical for the formation of skeletal muscle triad junctions by connecting the sarcoplasmic reticulum and T-tubules. Our findings suggest that loss of
JPH1
results in a congenital myopathy with prominent facial, bulbar and ocular involvement.
Anxiety and its relationship to demographic and personality traits data among special operations divers: a cross-sectional study
Authors: Zhao Houyu , Wen Y , Liang K , Huang J , Fang Y
Published: August 2024

Introduction

Special operation diving is becoming increasingly prevalent but has received less attention. The anxiety profile in special operation divers and its influencing factors remain unclear, posing great challenges to medical and psychological security of this unique population. The current study aimed to investigate the anxiety profile and to analyse the correlations between anxiety with demographic and personality traits data among special operation divers.

Methods

From July to October 2023, 650 special operation divers participated this analytical cross-sectional study. The Spielberg’s State-Trait Anxiety Inventory and the Neuroticism Extraversion Openness Five-Factor Inventory were used to evaluate anxiety and personality traits of special operation divers.

Results

27.2% and 30.3% special operation divers showed high scores on state anxiety and trait anxiety, respectively. Special operation divers who are 30 years or older and who have dived for 15 years or more are prone to higher level of trait anxiety and state anxiety (all p<0.001). Neuroticism showed a significantly positive correlation with both trait anxiety (r=0.675, p<0.001) and state anxiety (r=0.674, p<0.001). Extraversion, openness, agreeableness and conscientiousness are all negatively correlated with both trait anxiety and state anxiety (r=−0.670 to −0.400, all p<0.001). Additionally, significant differences in neuroticism, extraversion, openness, agreeableness and conscientiousness were observed between the high anxiety group and the low anxiety group (all p<0.001).

Conclusion

The prevalence of trait anxiety and state anxiety are both relatively high among special operation divers. Individuals with older age and longer diving years are more prone to be anxious. Higher neuroticism, lower extraversion, lower openness, lower agreeableness and lower conscientiousness may be predictors of higher trait anxiety and higher state anxiety.
Idiopathic pulmonary vein thrombosis: an under-recognised source of embolic stroke
Authors: Reddy Y Muralidhar , Parida Subhendu , Reddy Manvitha , Christopher Johann , Pidaparthi Lalitha , Gattu Abhinay Kumar , Murthy J M K
Published: August 2024

Embolic stroke due to pulmonary vein thrombosis is rare but may be associated with lung and left atrial tumours, pulmonary surgery, atrial fibrillation and radiofrequency ablation. It is very rarely idiopathic. A 23-year-old man developed acute onset of a left partial third nerve palsy and left ataxic hemiparesis. His MR scan of the brain showed an acute infarct in the left midbrain and left thalamus. CT angiogram found no steno-occlusive disease and transthoracic echocardiogram was normal. However, a transoesophageal echocardiogram showed a hyperechoic mass projecting from the right inferior pulmonary vein, confirmed on cardiac MR scan to be a right inferior pulmonary vein thrombus. A cardiac loop recorder did not capture an atrial arrhythmia. CT scan of the chest found no significant abnormality in the pulmonary parenchyma. Investigations for hypercoagulable state were negative. He took dabigatran for 6 months with complete resolution of thrombus.
Efficacy of BAFF inhibition and B-cell depletion in non-obese diabetic mice as a spontaneous model for Sjögren’s disease
Authors: Felten Renaud , Foray Anne-Perrine , Schneider Pascal , Marquet Cindy , Pecquet Coralie , Monneaux Fanny , Dumortier Hélène , Sibilia Jean , Valette Fabrice , Chatenoud Lucienne , Gottenberg Jacques-Eric
Published: August 2024

Introduction

The therapeutic interest of targeting B-cell activating factor (BAFF) in Sjögren’s disease (SjD) can be suspected from the results of two phase II clinical trials but has not been evaluated in an animal model of the disease. We aimed to evaluate the therapeutic efficacy of this strategy on dryness and salivary gland (SG) infiltrates in the NOD mouse model of SjD.

Material and methods

Female NOD mice between ages 10 and 18 weeks were treated with a BAFF-blocking monoclonal antibody, Sandy-2 or an isotype control. Dryness was measured by the stimulated salivary flow. Salivary lymphocytic infiltrates were assessed by immunohistochemistry. Blood, SGs, spleen and lymph-node lymphocyte subpopulations were analysed by flow cytometry. SG mRNA expression was analysed by transcriptomic analysis.

Results

BAFF inhibition significantly decreased SG lymphocytic infiltrates, which was inversely correlated with salivary flow. The treatment markedly decreased B-cell number in SGs, blood, lymph nodes and spleen and increased Foxp3+regulatory and CD3+CD4−CD8−double negative T-cell numbers in SGs.

Conclusion

A monoclonal antibody blocking BAFF and depleting B cells had therapeutic effectiveness in the NOD mouse model of SjD. The increase in regulatory T-lymphocyte populations might underlie the efficacy of this treatment.
Doxycycline post-exposure prophylaxis among men who have sex with men and transgender women in Belgium: awareness, use and antimicrobial resistance concerns in a cross-sectional online survey
Authors: Vanbaelen Thibaut , Rotsaert Anke , De Baetselier Irith , Platteau Tom , Hensen Bernadette , Reyniers Thijs , Kenyon Chris
Published: August 2024

Objectives

We aimed to assess the awareness, willingness to use and use of doxycycline post-exposure prophylaxis (doxyPEP) among men who have sex with men (MSM) and transgender women (TGW) in Belgium. Additionally, we aimed to identify factors associated with doxyPEP use and concerns regarding antimicrobial resistance (AMR).

Methods

Cross-sectional online survey among MSM and TGW in Belgium in April 2024. Participants were recruited through sexual networking applications and social media of community-based organisations. Numerical variables were compared with Wilcoxon rank-sum test and categorical variables with χ2or Fisher’s exact tests. Factors associated with doxyPEP use were assessed using logistic regression. Willingness to use doxyPEP and concerns about side effects/AMR were assessed before and after presenting a brief paragraph on the potential effects of doxyPEP on AMR.

Results

875 individuals initiated the survey. Almost all identified as men (860/875, 98.3%) with a median age of 40 years (IQR 32–48), 40.4% (n=352/875) had heard of doxyPEP and 9.4% (n=82/875) had used it, among whom the majority used it within the previous 6 months (70/81, 86.4%). In multivariable logistic regression, doxyPEP use was associated with reporting ≥1 sexually transmitted infection (STI) in the previous 12 months, engagement in chemsex, HIV status and pre-exposure prophylaxis use, and education level.

About 80% of the participants initially reported being willing to use doxyPEP, and about 50% reported being concerned about side effects. After reading about the potential effects of doxyPEP on AMR, willingness to use decreased to 60% and concerns of side effects/AMR increased to around 70%.

Conclusions

Approximately 1 in 10 MSM in Belgium reported using doxyPEP. A recent history of STIs and STI risk factors were positively associated with doxyPEP use. Importantly, concerns about AMR and side effect influenced willingness to use doxyPEP. If doxyPEP is introduced, informing patients about doxyPEP benefits and risks is crucial to enable informed decision-making.
Crystal Plasticity Model and Simulations for Single Crystal Magnesium
Authors: Xu Haobin , Sun Shuli
Published: August 2024

To further investigate interaction and competition among various deformation modes in magnesium, a crystal plasticity model incorporating slip, twin, and secondary slip and twin systems is established. This study extends recent molecular dynamics findings to the crystal plasticity framework, introducing a new slip hardening model that incorporates twin boundaries. The proposed unified twin hardening model suitable for both tensile and compressive twins, considers twin stages of nucleation, propagation and growth, thereby simulating twin saturation and coexistence of multiple twin variants. Initially applied to single crystal magnesium, the numerical results agree with experimental findings by Kelley and Hosford, demonstrating twin saturation. We observe that plastic contributions from secondary slip and twin are smaller than those from slip and twins in the parent phase. Furthermore, the plastic contribution from pyramidal I slip is preferred to pyramidal II slip. Next, to study the serious influence of voids on the stress–strain response of ductile solids during manufacturing, the proposed model is then applied to single crystal magnesium containing a void along [Formula: see text]-axis tension and compression. Both simulations confirm the validity of our crystal plasticity model and its potential to analyze future experimental and molecular dynamic findings.