bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceptual and neural measures of spectral and temporal cue strength in speech perception
Authors: Pichaitanaporn Jitpakorn , Eddins David A. , Ozmeral Erol J. , Higgins Nathan C. , Secor Carrie , Eddins Ann C.
Published: November 2023

Many listeners experience difficulty understanding speech in noise that may result from limited ability to use important acoustic cues, such as spectral and temporal features. One way of assessing deficits related to perceptual or neural processing is to enhance or degrade specific cues and measure the impact on behavior or neural coding. To do so, we combined a target-word identification task with simultaneous EEG measurement in 20 young and 20 older normal-hearing listeners. Coordinate Response Measure sentences were manipulated in the spectral modulation (SM) and temporal modulation (TM) domains (neutral, degraded, enhanced) and presented in four-talker babble in both passive and attention conditions. Multivariate temporal response function (mTRF) analyses were used to evaluate cortical tracking of the speech envelope. Speech perception in younger listeners improved for both SM and TM enhancement, but older listeners only benefited from TM enhancement. Both groups showed stronger cortical tracking for attention versus passive listening, but only older listeners showed tracking changes across SM and TM conditions. Cortical tracking and perceptual results in older listeners are consistent with cognitive aging theories suggesting that cortical processing changes with age involve both compensation and dedifferentiation to help maintain auditory perceptual performance.
Modulation of auditory processing by non-auditory brain areas: Effects of acoustic trauma
Authors: Zimdahl Jack W. , Barry Kristin M. , Rodger Jennifer , de Vis Chenae , Robertson Donald , Mulders Wilhelmina
Published: November 2023

Acoustic trauma (AT) induced hearing loss elicits plasticity in the form of altered spontaneous firing throughout the central auditory pathway, including at the level of the medial geniculate nucleus (MGN). Non-auditory areas such as the prefrontal cortex (PFC) and amygdala are thought to modulate auditory processing in the MGN, which may play a role in sensory gating. In our laboratory, we investigated the functionality of inputs from the PFC and amygdala on MGN activity in different animal models (rat and guinea pig) both without and with AT. The effects of AT on auditory thresholds were investigated using auditory brainstem response (ABR) recordings or compound action potential recordings of the auditory nerve. To test circuitry functionality, we used single neuron recordings in the MGN combined with electrical stimulation of the PFC or amygdala. Our data showed, first, that electrical stimulation of either the PFC or amygdala resulted in a variety of effects within the MGN (facilitation, inhibition, or no effect) and, second, that AT and subsequent hearing loss significantly increased the magnitude of inhibition. This change in inhibition may represent a compensatory mechanism in response to the increased spontaneous activity in the central auditory pathway known to occur following hearing loss.
Improving auditory-perceptual evaluation of disordered voice quality using a novel three-dimensional matching task
Authors: Park Yeonggwang , Anand Supraja , Awan Shaheen N. , Shrivastav Rahul , Eddins David A.
Published: November 2023

Current methods of auditory-perceptual evaluation of disordered voice quality using ordinal or interval scales have limited reliability and precision to quantify the magnitude of change in response to disorder progression or treatment. Matching tasks with synthetic comparison sounds have emerged as a more effective alternative, reducing biases and providing adjustable comparative values to represent perceived magnitude of change in quality. Previous studies have focused on the individual dimensions of breathiness, roughness, and strain separately and indicate covarying voice qualities may impact listener judgments. Here we investigate a three-dimensional matching (3-DMA) task where three variables, each representing a major quality dimension, can be adjusted concurrently. The comparison sound was a low-pass filtered sawtooth waveform (f o = 151 Hz) mixed with noise. Independent variables for matching were the signal-to-noise ratio for breathiness, amplitude modulation depth for roughness, and bandpass filter gain for strain. Listeners used sliders to adjust each variable, matching all three dimensions of 26 natural voice samples, selected to contain wide variation in all three dimensions. Preliminary results from five listeners demonstrated good reliability, similar to that observed in previous single-variable matching tasks for individual voice qualities. The results support the feasibility of the 3-DMA task. [Work supported by NIH R01DC009029.]
Passive acoustic glider for marine acoustic environment characterization
Authors: Jiang Yong-Min , Dosso Stan , Troiano Luigi , Maguer Alain
Published: November 2023

Acoustic payload-equipped underwater gliders have great potential for assessing the marine soundscape (oceanic acoustic environment), including characterizing properties of the sound field, of acoustic sources, and of the marine environment (water column and seabed). This talk presents observations and analysis of passive acoustic recordings carried out by gliders during the 2017 Seabed Characterization Experiment (SBCEX17). Two Teledyne Webb Research Slocum gliders equipped with omni-directional hydrophones were deployed as virtual acoustic moorings in 72 m deep water on the New England Mud Patch for time periods of ∼6 days for one glider and ∼3 days for the other. Acoustic recordings collected by the gliders captured the marine soundscape, including natural ambient noise, marine-life sounds, ship noise, and acoustic signals transmitted by the SBCEX17 participants. The acoustic environment in the water column is characterized in terms of the acoustic power spectral density as a function of time, depth, and frequency. As an example of the use of passive acoustic gliders for environmental characterization, Bayesian geoacoustic inversion for seabed properties is presented, making use of recordings of controlled sources associated with SBCEX17. [Work supported by the Office of Naval Research.]
Needs of musicians during performance, without electronic amplification, in Concert Halls and Opera Houses
Authors: Harkness Edward L.
Published: November 2023

Drawing on experience of having listened to music in 60 concert halls and opera houses around the World, conducted experimental stage and orchestra pit modifications for live performance with audiences, analyzed the onset characteristics of musical instruments and their attack sequences; manipulated the distribution of acoustic energy using stage furniture with performer responses; and taught acoustics for 40 years, the author offers insights into the design of stages and orchestra pits for the performance of music without electronic amplification, in the context of his experience as a musician, architect, and engineer. In the orchestra pit of the Sydney Opera House: A second desk first violinist said he could not hear his instrument before the furniture was installed; and said after the furniture had been installed, “I am like thunder!” The tympani player asked, “What have you done? My instruments are alive!” In the Macquarie Auditorium, a violinist playing her Stradivarius violin said, “I used to dread playing in that auditorium now I am soaring.” The Australian Chamber orchestra refused to make a recording in the Gore Hill ABC TV Studio, without the stage furniture. What was done in several auditoria and responses from musicians is described in the paper.
The Estill Voice Model: A paradigm for voice training and treatment
Authors: Steinhauer Kimberly
Published: November 2023

For over 40 years, the Estill Voice Model (EVM) has defined voice quality according to movement of anatomy and physiology. EVM addresses the daunting degrees of freedom issue in voice motor control by isolating Craft of voice production from Artistry and Performance Metaphysics. The EVM proposes an integrated implicit-explicit approach for voice motor learning that flows through all training and therapy protocols. Implicit instructions include auditory-perceptual prompts (e.g., quack like a duck to produce “twang”) and explicit prompts train physiologic conditions of the vocal anatomy correlated with the voice quality (e.g., narrow your aryepiglottic sphincter to produce “twang”). Estill exercises address power, source, and filter properties of voice production, and include narrowing the aryepiglottic sphincter for “ring” in opera and belt and for increased power in hypofunctional voices, and varying vocal fold mass for register shifts and optimizing contact for hyperfunctional voices. Patients learn to feel, see, and hear the voice via multiple feedback modes including hand gestures, magnitude estimation of bodily kinesthetic effort, visual acoustic cues in real-time spectral analysis programs. This presentation will highlight objective measurement science and clinical evidence for using Estill exercises in treatment for all voices, from the novice speaker to the expert performer.
Functional Electrical Stimulation (FES)—Therapeutical potentials for presbyphonia
Authors: Kniesburges Stefan , Jakubass Bernhard , Gerstenberger Claus , Kirsch Andrijana , Peters Gregor , Semmler Marion , Gugatschka Markus , Dollinger Michael
Published: November 2023

Presbyphonia, an age-related decrease in voice quality is a consequence of vocal muscle atrophy. Functional Electrical Stimulation (FES) was introduced as a potential treatment to increase the muscle volume. In this study, we analyzed the effects of FES using ex vivo sheep larynx models. To stimulate the thyroarytenoid muscle, electrodes were implanted at the recurrent laryngeal nerve of 12 sheep (10 y). Stimulation was applied to six sheep for 9 weeks. Afterwards, the excised larynges were fixated in a mechanical setup and analyzed. For different elongations of the VFs, the acoustic signal, the subglottal pressure, and the VF motion were recorded simultaneously. The postprocessing was performed with the Glottis Analysis Tools (GAT) software and SPSS. The results show that the vibration characteristics and sound quality improved for the stimulated larynges. The vibration showed a higher degree of glottis closure (GGI) and symmetry (PAI and ASI), as well as a faster glottis closure (MADR) achieved by FES. Consequently, the sound signal exhibited a larger number of tonal sound components (CPP). Furthermore, a higher correlation between acoustic and subglottal pressure was found indicating an enhanced coupling between sub- and supraglottal regions. The results suggest that FES could be a possible therapy for presbyphonia.
Experiments with coated surfaces to generate sound waves in water
Authors: Hostombe Kevin , Avsic Tom , Sachau Delf
Published: November 2023

Sources for underwater sound have a wide range of applications, such as active sonar, navigation, and underwater communication. Particularly, sources with large dimensions l, such as a coating on a boat structure, can be suitable for generating low-frequency underwater sound. In this context, low-frequency refers to wavelength λ in water that fall within the range of 40 l > λ > 1,5 l. In this study, a sample of an active surface for generating underwater sound is created by attaching an array of 18 circular piezoelectric actuators to a glass-fiber reinforced plastic (GRP) plate. The array and the plate are coated with a potting compound that possesses the same acoustic properties as water. This coating physically separates the actuators from the water. The actuators can be individually controlled to analyze different configurations. The radiation characteristics of the active surface are investigated in an underwater test range with free field conditions, specifically for low-frequencies. Additionally, the interaction among the actuators and between the actuators and the GRP-plate are analyzed.
Design of performance-weighted blended mode filters for underwater experiments
Authors: Wage Kathleen E. , Chakrabarti Bhargabi
Published: November 2023

Normal mode signals are valuable in ocean acoustic tomography and source localization, assuming that they can be separated using spatial or temporal filtering. Common spatial mode filters include the matched filter (MF) [Ferris, JASA, 1972] and the pseudo-inverse (PI) filter [Tindle et al., JASA, 1978]. Choosing a filter and its parameters, e.g., the PI filter rank, requires knowledge that is not readily available. For instance, it is unlikely that the levels of ambient noise or interference from other modes is known a priori. To address this problem, Chakrabarti and Wage [IEEE Oceans, 2021, 2022] developed a Performance-Weighted Blended mode filtering algorithm that adapts quickly to changing conditions and achieves better performance than a single fixed mode filter. The PWB filter blends a set of PI filters of varying ranks, including a rank-1 PI filter (MF). A PI filter can suppress interference from neighboring modes but is more vulnerable to noise than the MF, which has the maximum white noise gain. This talk explores practical aspects of the PWB implementation, including how to select the set of filters to blend given realistic underwater noise conditions. We will show experimental and simulated data to illustrate performance in different environments. [Work supported by ONR.]
A method to improve the update rate of underwater acoustic positioning system
Authors: Choi Youngchol , Kim Sea-Moon , Cho Ara , Park Jong-Won
Published: November 2023

Underwater positioning system obtains relative position between a transponder and a transceiver by measuring round trip time (RTT) and angle of arrival. The position update rate (PUR) cannot be greater than 1/RTT, and when one transceiver locates multiple transponders, the PUR becomes smaller. This paper proposes a method to increase the PUR. The proposed method minimizes “idle time” by allowing the transceiver to send additional pings without packet transmission-reception collisions, rather than waiting for the response to the previous ping sent to the transponder. It is essential that the reception (transmission) of the ping and the transmission (reception) of the response should not be overlapped in the transponder (transceiver). In order to avoid these collisions, the ping transmission time is adaptively determined by considering the bound of packet reception times drawn by ping duration (PD), response signal duration (RD), and the maximum relative speed. In addition, the transceiver assigns a delay before sending the response signal upon receiving each ping. These adaptive features effectively adapt to changes due to mobility. We derive a theoretical upper bound of the PUR and verify this bound by computer simulations. [Work supported by KIMST funded by the Agency of Korea Coast Guard (KIMST-20210547).]
The Biomechanics Research and Innovation Challenge: Development, Implementation, Uptake, and Reflections on the Inaugural Program
Authors: Coltman Celeste E. , Barzan Martina , Besomi Manuela , Brackley Victoria , Bousie Jaquelin A. , Choisne Julie , Diamond Laura E. , Dick Taylor J.M. , D’Souza Nicole , Fien Samantha , Fong Yan Alycia , Gho Sheridan A. , Giraldo-Pedroza Alexandra , Hutchinson Laura A. , Hutchison Laura V. , Kean Crystal O. , Kirk Maddison M. , Lewis Amy , Maharaj Jayishini N. , Maher Nina , Mann Kerry J. , Martin Suzanne , Mickle Karen J. , Nasseri Azadeh , Oon Isobel H. , Purdie Rory , Quinlan Shayan L. , Radcliffe Ceridwen R. , Snodgrass Suzanne J. , Verma Siddharth , Hall Michelle
Published: November 2023

Biomechanics as a discipline is ideally placed to increase awareness and participation of girls and women in science, technology, engineering, and mathematics. A nationwide Biomechanics and Research Innovation Challenge (BRInC) centered on mentoring and role modeling was developed to engage high school girls (mentees) and early-mid-career women (mentors) in the field of biomechanics through the completion of a 100-day research and/or innovation project. This manuscript describes the development, implementation, and uptake of the inaugural BRInC program and synthesizes the research and innovation projects undertaken, providing a framework for adoption of this program within the global biomechanics community. Eighty-seven high school girls in years 9 and 10 (age range: 14–16 y) were mentored in teams (n = 17) by women in biomechanics (n = 24). Using a design thinking approach, teams generated solutions to biomechanics-based problem(s)/research question(s). Eight key reflections on program strengths, as well as areas for improvement and planned changes for future iterations of the BRInC program, are outlined. These key reflections highlight the innovation, impact, and scalability of the program; the importance of a program framework and effective communication tools; and implementation of strategies to sustain the program as well as the importance of diversity and building a sense of community.
PD-1 inhibits T cell actin remodeling at the immunological synapse independently of its signaling motifs
Authors: Paillon Noémie , Mouro Violette , Dogniaux Stéphanie , Maurin Mathieu , Saez Pons Juan-José , Ferran Hermine , Bataille Laurence , Zucchetti Andrés Ernesto , Hivroz Claire
Published: November 2023

Engagement of the receptor programmed cell death molecule 1 (PD-1) by its ligands PD-L1 and PD-L2 inhibits T cell–mediated immune responses. Blocking such signaling provides the clinical effects of PD-1–targeted immunotherapy. Here, we investigated the mechanisms underlying PD-1–mediated inhibition. Because dynamic actin remodeling is crucial for T cell functions, we characterized the effects of PD-1 engagement on actin remodeling at the immunological synapse, the interface between a T cell and an antigen-presenting cell (APC) or target cell. We used microscopy to analyze the formation of immunological synapses between PD-1
+
Jurkat cells or primary human CD8
+
cytotoxic T cells and APCs that presented T cell–activating antibodies and were either positive or negative for PD-L1. PD-1 binding to PD-L1 inhibited T cell spreading induced by antibody-mediated activation, which was characterized by the absence of the F-actin–dense distal lamellipodial network at the immunological synapse and the Arp2/3 complex, which mediates branched actin formation. PD-1–induced inhibition of actin remodeling also prevented the characteristic deformation of T cells that contact APCs and the release of cytotoxic granules. We showed that the effects of PD-1 on actin remodeling did not require its tyrosine-based signaling motifs, which are thought to mediate the co-inhibitory effects of PD-1. Our study highlights a previously unappreciated mechanism of PD-1–mediated suppression of T cell activity, which depends on the regulation of actin cytoskeleton dynamics in a signaling motif–independent manner.
Selective cell lysis pressure on rare and abundant prokaryotic taxa across a shelf-to-slope continuum in the Northern South China Sea
Authors: Liu Lu , Zhong Kevin Xu , Chen Qi , Wang Yu , Zhang Ting , Jiao Nianzhi , Zheng Qiang
Published: November 2023

Microbial growth and mortality are fundamental to community assembly and drive the elemental biogeochemical cycles in the ocean. Virus-induced host lysis contributes, on average, half of prokaryotic mortality and has a substantial effect on composition and diversity of marine microbes. Nevertheless, virus-mediated taxon-specific cell lysis is few studied to date. In the present study, we investigated the taxon-specific cell lysis and estimated its contribution to the variations of community composition in rare and abundant microbial taxa. The dominant taxa
Prochlorococcus
,
Synechococcus
, SAR11, and
Rhodobacteraceae
displayed lower cell lysis index (CLI, the rate of extracellular to intracellular rRNA) in surface seawater. Meanwhile,
Alteromonas
,
Pseudomonas,
and
Halomonas
had high CLI values in the bottom seawater. Cell lysis contributed a larger percentage of variation in rare taxa (5.0%–9.4%) than in abundant taxa (0.1%–1.7%). Furthermore, linear regression analysis indicated that rare taxa were more likely to experience higher viral lysis pressure relative to abundant taxa. Our findings provide insight into the impact of virus-mediated cell lysis on prokaryotic community structure and diversity and further improve our understanding of the various abiotic and biotic factors contributing to community assembly in the ocean.

IMPORTANCE

Virus-induced host lysis contributes up to 40% of total prokaryotic mortality and plays crucial roles in shaping microbial composition and diversity in the ocean. Nonetheless, what taxon-specific cell lysis is caused by viruses remains to be studied. The present study, therefore, examined the taxon-specific cell lysis and estimated its contribution to the variations in the rare and abundant microbial taxa. The results demonstrate that taxon-specific mortality differed in surface and bottom of the coastal environment. In addition, active rare taxa are more susceptible to heightened lytic pressure and suggested the importance of viral lysis in regulating the microbial community composition. These results improve our understanding of bottom-up (abiotic environmental variables) and top-down (viral lysis) controls contributing to microbial community assembly in the ocean.
IL-17 receptor A functions to help maintain barrier integrity and limit activation of immunopathogenic response to
H. pylori
infection
Authors: Brackman Lee C. , Dixon Beverly R. E. A. , Bernard Margaret , Revetta Frank , Cowell Rebecca P. , Meenderink Leslie M. , Washington M. Kay , Piazuelo M. Blanca , Algood Holly M. Scott
Published: November 2023

Activation of Th17 cell responses, including the production of IL-17A and IL-21, contributes to host defense and inflammatory responses by coordinating adaptive and innate immune responses. IL-17A and IL-17F signal through a multimeric receptor, which includes the IL-17 receptor A (IL-17RA) subunit and the IL-17RC subunit. IL-17RA is expressed by many cell types, and data from previous studies suggest that loss of IL-17 receptor is required to limit immunopathology in the
Helicobacter pylori
model of infection. Here, an

Il17ra
-/-

mouse was generated on the FVB/n background, and the role of IL-17 signaling in the maintenance of barrier responses to
H. pylori
was investigated. Generating the

Il17ra
-/-

on the FVB/n background allowed for the examination of responses in the paragastric lymph node and will allow for future investigation into carcinogenesis. While uninfected

Il17ra
-/-

mice do not develop spontaneous gastritis following
H. pylori
infection,

Il17ra
-/-

mice develop severe gastric inflammation accompanied by lymphoid follicle production and exacerbated production of Th17 cytokines. Increased inflammation in the tissue, increased IgA levels in the lumen, and reduced production of Muc5ac in the corpus correlate with increased
H. pylori-
induced paragastric lymph node activation. These data suggest that the cross talk between immune cells and epithelial cells regulates mucin production, IgA production, and translocation, impacting the integrity of the gastric mucosa and therefore activating of the adaptive immune response.
LORF9 of Marek’s disease virus is involved in the early cytolytic replication of B lymphocytes and can act as a target for gene deletion vaccine development
Authors: Zhu Xiaojing , Wang Lele , Gong Lele , Zhai Yunyun , Wang Rui , Jin Jiaxin , Lu Wenlong , Zhao Xuyang , Liao Yifei , Zhang Gaiping , Zhuang Guoqing , Sun Aijun
Published: November 2023

Marek’s disease (MD) is a poultry disease characterized by severe immunosuppression and the development of T cell lymphomas caused by Marek’s disease virus (MDV). Our study focuses on the role of the viral
LORF9
gene in MD pathogenesis and vaccine development. We found that a
LORF9
gene deletion mutant (Md5BAC Δ
LORF9
) showed significantly reduced pathogenicity compared with the parental strain. The
LORF9
gene is essential for the early cytolytic infection in B cells. Interestingly, Md5BAC Δ
LORF9
provided adequate immunological protection against very virulent MDV challenge and induced a distinct host immune response compared with the CVI988/Rispens vaccine strain. Transcriptome analysis revealed that the deletion of
LORF9
led to a significantly different expression of innate immunity-associated genes. Overall, our study provides insights into the role of LORF9 in MD pathogenesis and highlights its importance in MDV gene deletion vaccine development.

IMPORTANCE

Marek’s disease virus (MDV) is a highly infectious and oncogenic virus that can induce severe T cell lymphomas in chickens. MDV encodes more than 100 genes, most of which have unknown functions. This work indicated that the
LORF9
gene is necessary for MDV early cytolytic replication in B lymphocytes. In addition, we have found that the
LORF9
deletion mutant has a comparative immunological protective effect with CVI988/Rispens vaccine strain against very virulent MDV challenge. This is a significant discovery that LORF9 can be exploited as a possible target for the development of an MDV gene deletion vaccine.
Diabetes knowledge and foot care practices among type 2 diabetes patients attending the chronic ambulatory care unit of a public health hospital in eastern Ethiopia: a cross-sectional study
Authors: Letta Shiferaw , Goshu Abel Tibebu , Sertsu Addisu , Nigussie Kabtamu , Negash Abraham , Yadeta Tesfaye Assebe , Bulti Fekadu Aga , Geda Biftu , Dessie Yadeta
Published: November 2023

Objective

To assess diabetes knowledge and foot care practices among type 2 diabetes patients.

Design

An institution-based cross-sectional study was undertaken from 1 January to 31 January 2021.

Setting

Eastern Ethiopia.

Participants

Randomly selected type 2 diabetes patients who were available during the data collection period were included.

Outcomes

Patients’ diabetes knowledge was assessed with the revised diabetes knowledge test questionnaire. Five items were used to evaluate foot self-care practices.

Results

The study population comprised of 549 patients. About 52.5% of the patients had adequate diabetes knowledge (95% CI: 48.2% to 56.7%). Patients with an educational level of secondary school and above (adjusted OR (AOR): 2.04, 95% CI: 1.13 to 3.71), (AOR: 5.28, 95% CI: 2.28 to 12.22), and those with medium and above wealth status (AOR: 3.81, 95% CI: 2.24 to 6.47), (AOR: 3.46, 95% CI: 1.98 to 6.04), were found to have better odds of having adequate diabetes knowledge. However, those aged >55 years (AOR: 0.47, 95% CI: 0.22 to 0.99) were found to have lower odds of adequate diabetes knowledge.Of the total included patients, 20.2% (95% CI: 16.9% to 23.8%) had good foot care practices. Knowledge of the target fasting plasma glucose (AOR: 3.18, 95% CI: 1.94 to 5.22) and adequate diabetes knowledge (AOR: 3.40, 95% CI: 1.95 to 5.91) were significantly associated with good foot care practices.

Conclusion

According to this study, about half of individuals with type 2 diabetes have adequate levels of knowledge about the disease. In addition, only one out of every five patients has good foot care habits. Diabetes education should emphasise the significance of rigorous adherence to daily foot care practices.
Metformin in the prevention of type 2 diabetes after gestational diabetes in postnatal women (OMAhA): a UK multicentre randomised, placebo-controlled, double-blind feasibility trial with nested qualitative study
Authors: Bolou Angeliki , Drymoussi Zoe , Lanz Doris , Amaefule Chiamaka Esther , Gonzalez Carreras Francisco Jose , Pardo Llorente Maria del Carmen , Dodds Julie , Pizzo Elena , Thomas Amy , Heighway James , Harden Angela , Sanghi Anita , Hitman Graham , Zamora Javier , Pérez Teresa , Huda Mohammed S B , Thangaratinam Shakila
Published: November 2023

Objective

To determine the feasibility of a definitive trial of metformin to prevent type 2 diabetes in the postnatal period in women with gestational diabetes.

Design

A multicentre, placebo-controlled, double-blind randomised feasibility trial with qualitative evaluation.

Setting

Three inner-city UK National Health Service hospitals in London.

Participants

Pregnant women with gestational diabetes treated with medication.

Interventions

2 g of metformin (intervention) or placebo (control) from delivery until 1 year postnatally.

Primary outcome measures

Rates of recruitment, randomisation, follow-up, attrition and adherence to the intervention.

Secondary outcome measures

Preliminary estimates of glycaemic effects, qualitative exploration, acceptability of the intervention and costs.

Results

Out of 302 eligible women, 57.9% (175/302) were recruited. We randomised 82.3% (144/175) of those recruited, with 71 women in the metformin group and 73 women in the placebo group. Of the participants remaining in the study and providing any adherence information, 54.1% (59/109) took at least 75% of the target intervention dose; the overall mean adherence was 64% (SD 33.6). Study procedures were found to be acceptable to women and healthcare professionals. An increased perceived risk of developing type 2 diabetes, or a positive experience of taking metformin during pregnancy, encouraged participation and adherence to the intervention. Barriers to adherence included disruption to the medication schedule caused by the washout periods ahead of each study visit or having insufficient daily reminders.

Conclusions

It is feasible to run a full-scale definitive trial on the effectiveness of metformin to prevent type 2 diabetes in women with gestational diabetes, during the early postnatal period. Adherence and engagement with the study could be improved with more regular reminders and potentially the addition of ongoing educational or peer support to reinforce messages around type 2 diabetes prevention.

Trial registration number

ISRCTN20930880.
Comparison of drug-coated balloon angioplasty versus standard medical therapy on recurrent stroke and mortality rates among patients with symptomatic intracranial atherosclerotic stenosis: protocol for a systematic review and meta-analysis
Authors: Sun Yixin , Luo Jichang , Gong Haozhi , Xu Ran , Zhang Xiao , Yang Bin , Ma Yan , Wang Tao , Jiao Liqun
Published: November 2023

Introduction

Stroke remains the second leading cause of death worldwide, a common cause of which is intracranial atherosclerotic stenosis (ICAS). Medical treatment is recommended as first-line therapy for treating ICAS, but the recurrence rate remains high. Drug-coated balloon (DCB) angioplasty has been designed to lower the risk of recurrent stenosis, holding therapeutic promise in the treatment of ICAS. However, the benefits of DCB require further evaluation.

Methods and analysis

The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols was followed to develop this protocol. We will systematically search online databases including Cochrane Central Register of Controlled Trials, PubMed, Web of Science, EMBASE, China Biological Medicine Database, ClinicalTrials.gov and WHO ICTRP from 1 January 2011 to the date of search. This will be supplemented by a manual search of unpublished and ongoing trials to manually select articles for inclusion. Inclusion criteria are randomised or quasi-randomised clinical trials and observational studies that investigated DCB or medical treatment for patients with a symptomatic ICAS of 50%–99%. The primary outcome is short-term composite safety including death of any cause, or non-fatal stroke. Secondary outcomes include long-term death or stroke, restenosis, neurological rehabilitation, quality of life and other complications. The available data will be analysed using meta-analysis, if appropriate. The evaluation of heterogeneity and biases will be guided by the Cochrane Handbook for Systematic Reviews of Interventions.

Ethics and dissemination

This systematic review does not require ethical approval as all available data from eligible studies will be anonymous with no concerns regarding privacy. Our findings will be disseminated through international conferences and peer-reviewed publications. Additional data from the study are available on request to corresponding authors via email.

PROSPERO registration number

CRD42022341607.
High-dose versus low-dose intravenous nitroglycerine for sympathetic crashing acute pulmonary edema: a randomised controlled trial
Authors: Siddiqua Naazia , Mathew Roshan , Sahu Ankit Kumar , Jamshed Nayer , Bhaskararayuni Jyothiswaroop , Aggarwal Praveen , Kumar Akshay , Khan Maroof Ahmad
Published: November 2023

Objectives

Sympathetic crashing acute pulmonary edema (SCAPE) is a subset of heart failure with a dramatic presentation. The unique physiology of this condition requires a different management strategy from the conventional practice. The trial objective was to compare the efficacy of high-dose and low-dose GTN in patients with SCAPE.

Methods

This was an open-label randomised control trial conducted in a tertiary care teaching hospital in India from 11 November 2021 to 30 November 2022. Consenting participants were randomised to high-dose GTN or conventional low-dose GTN. The primary outcome was symptom resolution at 6 hours and 12 hours. Secondary outcomes included intubation rates, admission rates, length of hospital stay, and any short-term adverse effects of GTN and major adverse cardiac events (MACE) at 30 days.

Results

Fifty-four participants were included (26 high-dose GTN, 26 low-dose GTN). At 6 hours, symptom resolution was seen in 17 patients (65.4%) in the 'high-dose' group, compared with 3 (11.5%) in the 'low-dose' group (p<0.001). At 12 hours, 88.5% of patients had a clinical resolution in the 'high-dose' arm versus 19.5% in 'low-dose' arm . The low-dose group had longer median hospital stay (12 hours vs 72 hours), more frequent MACE (3.8% vs 26.9%, p=0.02) and a higher intubation rate (3.8% vs 19.2%, p=0.08). The only short-term adverse effect seen was a headache in both the groups.

Conclusion

In SCAPE, patients receiving high-dose GTN (>100 mcg/min) had earlier symptom resolution compared with the conventional ‘low dose’ GTN without any significant adverse effects.

Trial registration

Clinical trial registry of India (CTRI/2021/11/037902).
Sexual orientation, gender expression and socioeconomic status in the National Longitudinal Study of Adolescent to Adult Health
Authors: Hernandez Stephanie M. , Halpern Carolyn T. , Conron Kerith J.
Published: November 2023

Background

Socioeconomic status (SES) is a fundamental contributor to health, yet it is rarely examined relative to gender expression, particularly gender non-conformity and sexual orientation.

Methods

We use data from 11 242 Wave V respondents (aged 33–44) in the National Longitudinal Study of Adolescent to Adult Health (2016–2018) to examine associations between socially assigned gender expression, sexual orientation and SES, in logistic and multinomial regression models stratified by sex assigned at birth.

Results

Among both women and men a general pattern of heightened risk for lower SES among gender non-conforming sexual minorities relative to gender conforming heterosexuals was observed. Gender non-conforming heterosexuals were also at elevated risk of lower SES compared with their conforming heterosexual peers.

Conclusion

Socioeconomic differences by sexual orientation and gender expression have important implications for understanding health disparities among gender non-conforming sexual minorities and their gender conforming heterosexual counterparts.
Randomized, open-label, phase II, biomarker study of immune-mediated mechanism of action of neoadjuvant subcutaneous trastuzumab in patients with locally advanced, inflammatory, or early HER2-positive breast cancer—Immun-HER trial (GOIRC-01-2016)
Authors: Pellegrino Benedetta , Tommasi Chiara , Serra Olga , Gori Stefania , Cretella Elisabetta , Ambroggi Massimo , Frassoldati Antonio , Bisagni Giancarlo , Casarini Chiara , Bria Emilio , Carbognin Luisa , Fiorio Elena , Mura Antonella , Zamagni Claudio , Gianni Lorenzo , Zambelli Alberto , Montemurro Filippo , Tognetto Michele , Todeschini Renata , Missale Gabriele , Campanini Nicoletta , Silini Enrico Maria , Maglietta Giuseppe , Musolino Antonino
Published: November 2023

Background

It is possible to induce immunomodulation in HER2-positive breast cancer (BC) by modifying the route of administration of trastuzumab.

Methods

In this multicenter randomized phase II trial, all enrolled patients (pts) with T2–T4d HER2-positive BC received 3 cycles of neoadjuvant treatment (NAT) with fluorouracil, epirubicin and cyclophosphamide every 3 weeks (q21), followed by docetaxel/pertuzumab plus intravenous trastuzumab (arm A) or, docetaxel/pertuzumab plus subcutaneous (SC) trastuzumab (arm B) q21x4 cycles. After surgical operation, each pt was treated with trastuzumab q21x14 cycles using the same SC or intravenous formulation of NAT. Primary endpoint was the proportion of subjects with high stromal tumor-infiltrating lymphocytes (sTILs) in postneoadjuvant residual disease (RD).

Results

Sixty-three pts (31 (arm A) and 32 (arm B)) were enrolled. Pathological complete response was obtained by 20/31 pts (64.5%; 95% CI 45.4% to 80.1%) in arm A and 19/32 pts (59.4%; 95% CI 40.1% to 76.3%) in arm B. High sTILs were observed in 27% and 46% of postneoadjuvant residual tumors in arms A and B, respectively. CD8+ T cells increased significantly in RDs of both arms (p=0.014 and 0.002 for arm A and B, respectively), whereas a significant decline in the level of CD4+ FoxP3+ regulatory T cells was observed only in arm B (p=0.016). A significant upregulation of PD-1 on sTILs was found in RD of pts enrolled in arm B (p=0.012), while programmed death-ligand 1 (PD-L1) was significantly overexpressed in residual tumors of arm A (p=0.02). A strong negative correlation was reported in arm B between expression of PD-L1 on pretreatment sTILs and CD3 expression on sTILs in RD (τ: −0.73). Grade≥3 AE incidence rates were similar between the two arms.

Conclusions

SC trastuzumab induced relevant sTILs enrichment, with favorable variations of immune parameters in HER2-positive BC pts with RD after NAT. Novel immunotherapy strategies should be tested to achieve SC-specific, antitumor immune response.

Trial registration number

NCT03144947, and EudraCT number: 2016-000435-41.
Assessment and predictive ability of the absolute neutrophil count in peripheral blood for in vivo CAR T cells expansion and CRS
Authors: Zhang Man , Long Xiaolu , Xiao Yi , Jin Jin , Chen Caixia , Meng Jiao , Liu Wanying , Liu Aichun , Chen Liting
Published: November 2023

Background

Chimeric antigen receptor (CAR) T cell therapy is an advanced and effective immunotherapy for relapsed or refractory B-cell malignancies. High expansion of CAR T cells in vivo and durable antitumor activity indicate a persistent therapeutic response. However, this treatment is linked to a high frequency of adverse events, such as cytokine release syndrome (CRS), which affects its efficacy and can even be life-threatening. At present, a variety of markers associated with clinical response and treatment toxicity after CAR T cells infusion have been reported. Although these biomarkers can act as effective indicators reflecting CAR T cells expansion as well as CRS, they fail to predict the expansion rate of CAR T cells. Hence, further investigation is urgent to find a new biomarker to fill this void.

Methods

We analyzed the association between the absolute neutrophil count (ANC) and CAR expansion and CRS in 45 patients with B-cell malignancies from two clinical trials. We proposed that ANC could be a practical biomarker for CAR T cells expansion and CRS, and conducted a feasibility analysis on its predictive ability.

Results

In this study, 17 B-cell hematological malignancy patients with anti-B-cell maturation antigen CAR-treated and 28 with CAR19/22 T-cell-treated were enrolled and divided into an ANC-absence group and an ANC-presence group. The results showed that ANC absence correlated positively with CAR expansion and the expansion rate. The ANC can be used as a predictive marker for CAR T cells expansion. Moreover, the patients with ANC absence experienced a more severe CRS, and ANC performed a predictive ability for CRS. In addition, the peak serum concentration of several cytokines involved in CRS was higher in patients with ANC absence.

Conclusion

Thus, we suggest ANC as an evaluative and predictive biomarker for CAR expansion and CRS during CAR T cell therapy, which can help to maximize clinical efficacy, reduce treatment-related toxicity and prolong survival.
Cardiovascular risk assessment in patients with antiphospholipid syndrome: a cross-sectional performance analysis of nine clinical risk prediction tools
Authors: Drosos George C , Konstantonis George , Sfikakis Petros P , Tektonidou Maria G
Published: November 2023

Objectives

This study aimed to assess the performance of cardiovascular risk (CVR) prediction models reported by European Alliance of Associations for Rheumatology and European Society of Cardiology recommendations to identify high-atherosclerotic CVR (ASCVR) patients with antiphospholipid syndrome (APS).

Methods

Six models predicting the risk of a first cardiovascular disease event (first-CVD) (Systematic Coronary Risk Evaluation (SCORE); modified-SCORE; Framingham risk score; Pooled Cohorts Risk Equation; Prospective Cardiovascular Münster calculator; Globorisk), three risk prediction models for patients with a history of prior arterial events (recurrent-CVD) (adjusted Global APS Score (aGAPSS); aGAPSSCVD; Secondary Manifestations of Arterial Disease (SMART)) and carotid/femoral artery vascular ultrasound (VUS) were used to assess ASCVR in 121 APS patients (mean age: 45.8±11.8 years; women: 68.6%). We cross-sectionally examined the calibration, discrimination and classification accuracy of all prediction models to identify high ASCVR due to VUS-detected atherosclerotic plaques, and risk reclassification of patients classified as non high-risk according to first-CVD/recurrent-CVD tools to actual high risk based on VUS.

Results

Spiegelhalter’s z-test p values 0.47–0.57, area under the receiver-operating characteristics curve (AUROC) 0.56–0.75 and Matthews correlation coefficient (MCC) 0.01–0.35 indicated moderate calibration, poor-to-acceptable discrimination and negligible-to-moderate classification accuracy, respectively, for all risk models. Among recurrent-CVD tools, SMART and aGAPSSCVD(for non-triple antiphospholipid antibody-positive patients) performed better (z/AUROC/MCC: 0.47/0.64/0.29 and 0.52/0.69/0.29, respectively) than aGAPSS. VUS reclassified 34.2%–47.9% and 40.5%–52.6% of patients classified as non-high-ASCVR by first-CVD and recurrent-CVD prediction models, respectively. In patients aged 40–54 years, >40% VUS-guided reclassification was observed for first-CVD risk tools and >50% for recurrent-CVD prediction models.

Conclusion

Clinical CVR prediction tools underestimate actual high ASCVR in APS. VUS may help to improve CVR assessment and optimal risk factor management.
Vector—towards quantum key distribution with small satellites
Authors: Miller Alexander V. , Pismeniuk Liubov V. , Duplinsky Alexey V. , Merzlinkin Vitaly E. , Plukchi Aleksandr A. , Tikhonova Kseniia A. , Nesterov Ivan S. , Sevryukov Dmitry O. , Levashov Sergey D. , Fetisov Vladimir V. , Krasnopejev Sergei V. , Bakhshaliev Ruslan M.
Published: November 2023

A satellite-constellation based global quantum network could allow secure quantum communication between remote users worldwide. Such a constellation could be formed of micro- or even nanosatellites, which have the advantage of being more cost-effective than larger expensive spacecrafts. At the same time, the features of quantum communication impose a number of technical requirements that are more difficult to meet when using small satellites. Full-fledged quantum communication has been demonstrated with neither a micro- nor a nanosatellite so far. The authors took up this challenge and have developed a 6U CubeSat weighting 9.5 kg. The satellite is to be launched in 2023 and has already successfully passed all the pre-flight tests. The mission is not yet intended for fully quantum communication. Nevertheless, the authors are testing such key functional elements as polarization reference-frame synchronization and acquisition, pointing and tracking system on it. Besides that, the payload accommodates a full-duplex telecommunication system operating at a bit rate of 50 Mbit/s: an up- and a downlink at wavelengths of 808 and 850 nm. After the satellite is launched, the main goal to be achieved is to demonstrate stable connection between it and an optical ground station and carry out multiple communication sessions. In quantum communication, generating secret keys from raw measurement data implies two-way exchange of significant amount of information and therefore availability of a classical communication channel with a high bandwidth is one of the crucial things. In the following mission, which envisages an overall quantum key distribution system, we plan to use the free-space optical link for such an exchange of data, whereas the RF link will only be used for telemetry and telecommand.
Synchronization in network motifs of three piecewise Rössler systems coupled in ring configuration
Authors: Uriostegui-Legorreta U. , Estevez-Delgado J. , Pérez-Aguilar H.
Published: November 2023

In this work, we study the synchronization in the network motifs of three piecewise Rössler systems that exhibit coexistence of two attractors, coupled in ring configuration, in particular a bidirectional auxiliary coupling. For this configuration, we analyze the interaction of the systems by varying the coupling strengths, in order to characterize the conditions under which complete synchronization between the three systems can be achieved. The numerical results prove that the interaction of various multistable chaotic systems causes different types of synchronization and very complex dynamics between the systems is achieved. We obtain complete synchronization between the three systems and find the range of values of the coupling strengths where the distinct types of synchronization occur.
ABO3 perovskite as well as BaF2, SrF2 and CaF2 bulk and surface F-center first principles predictions
Authors: Eglitis Roberts , Purans J. , Popov A. I. , Piskunov S. , Jia Ran , Kruchinin S. P.
Published: November 2023

We, at the ab initio level, simulated the rearrangement magnitudes of the adjacent neighboring ions, surrounding the (100) surface F-center in ABO3 perovskite matrixes. They are noticeably greater than the respective ionic shift magnitudes of the adjacent neighboring ions surrounding the bulk F-center. In ABO3 perovskites, the electron charge is noticeably better bounded on the inside of the bulk oxygen vacancy, as interior the respective (100) surface vacancy. The oxygen vacancy formation energy, located on the (100) surface of ABO3 perovskites, as a rule, is smaller as in the bulk. This slight energy distinction encourages the oxygen vacancy segregation from the ABO3 perovskite bulk to their (100) surfaces. The ABO3 complex oxide (100) surface F-center generated defect levels are positioned nearer to the (100) surface CB bottom than the bulk F-center generated respective defect levels. In contrary, the BaF2, SrF2 and CaF2, both, surface and bulk F-center charges are well localized inside the fluorine vacancy. The ionic rearrangement magnitudes of the adjacent neighboring ions, surrounding the surface and bulk F-centers in BaF2, SrF2 and CaF2 matrixes, are much smaller regarding the respective situation in ABO3 perovskites.