bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term safety of tenapanor in patients with irritable bowel syndrome with constipation in the T3MPO‐3 study
Authors: Lembo Anthony J. , Friedenberg Keith A. , Fogel Ronald P. , Edelstein Susan , Zhao Suling , Yang Yang , Rosenbaum David P. , Chey William D.
Published: September 2023

Background

Tenapanor, a first‐in‐class, minimally systemic inhibitor of intestinal sodium/hydrogen exchanger isoform 3 (NHE3), is approved for the treatment of irritable bowel syndrome with constipation (IBS‐C) in adults based on two randomized, placebo‐controlled, phase III studies (T3MPO‐1 [NCT02621892], T3MPO‐2 [NCT02686138]). The open‐label T3MPO‐3 extension study (NCT02727751) enrolled patients who completed these studies to investigate long‐term safety and tolerability of tenapanor.

Methods

Patients who completed T3MPO‐1 (16 weeks) or T3MPO‐2 (26 weeks) were eligible for enrollment in T3MPO‐3. Patients in T3MPO‐3 received open‐label tenapanor 50 mg twice a day for up to an additional 39 (T3MPO‐1) or 26 (T3MPO‐2) weeks. Treatment‐emergent adverse events (TEAEs) were evaluated in the entire T3MPO‐3 safety population and in patients who received a total of ≥52 weeks of tenapanor.

Key Results

A total of 312 patients were enrolled in T3MPO‐3; 90 received ≥52 weeks of tenapanor. TEAEs were reported in 117 (37.5%) patients in the safety population and in 52 (57.8%) patients who received ≥52 weeks of tenapanor. Diarrhea was the most common TEAE, occurring in 10.6% of the safety population and in 11.1% of patients who received ≥52 weeks of tenapanor. Most cases were mild or moderate in severity, with only two severe cases reported in the safety population. No deaths occurred during the T3MPO‐3 study.

Conclusions

Tenapanor was tolerable over ≥52 weeks of treatment and showed similar safety to that seen in shorter studies. Combined results of the T3MPO studies indicate that tenapanor is a valuable new treatment option for patients with IBS‐C.
Interaction of PALE CRESS with PAP2/pTAC2 and PAP3/pTAC10 affects the accumulation of plastid‐encoded RNA polymerase complexes in Arabidopsis
Authors: Wang Xiaomin , Qi Yafei , Liu Na , Zhang Qiaoxin , Xie Sha , Lei Yang , Li Bilang , Shao Jingxia , Yu Fei , Liu Xiayan
Published: September 2023

The transcription of photosynthesis genes in chloroplasts is largely mediated by the plastid‐encoded RNA polymerase (PEP), which resembles prokaryotic‐type RNA polymerases, but with plant‐specific accessory subunits known as plastid transcriptionally active chromosome proteins (pTACs) or PEP‐associated proteins (PAPs). However, whether additional factors are involved in the biogenesis of PEP complexes remains unknown.

Here, we investigated the function of an essential gene, PALE CRESS (PAC), in the accumulation of PEP complexes in chloroplasts.

We established that an Arabidopsis leaf variegation mutant, variegated 6‐1 (var6‐1), is a hypomorphic allele of PAC. Unexpectedly, we revealed that a fraction of VAR6/PAC is associated with thylakoid membranes, where it interacts with PEP complexes. The accumulation of PEP complexes is defective in both var6‐1 and the null allele var6‐2. Further protein interaction assays confirmed that VAR6/PAC interacts directly with the PAP2/pTAC2 and PAP3/pTAC10 subunits of PEP complexes. Moreover, we generated viable hypomorphic alleles of the essential gene PAP2/pTAC2, and revealed a genetic interaction between PAC and PAP2/pTAC2 in photosynthesis gene expression and PEP complex accumulation.

Our findings establish that VAR6/PAC affects PEP complex accumulation through interactions with PAP2/pTAC2 and PAP3/pTAC10, and provide new insights into the accumulation of PEP and chloroplast development.
Preliminary effects of a WeChat‐based educational intervention on social participation among older adults in a community
Authors: Liang Jiagui , Liu Jun‐E , Mak Yim Wah , Sun Liu
Published: September 2023

Background

The social participation of older people should be encouraged, as it is fundamental to their well‐being and the practice of aged care. Therefore, the ability of older persons to participate in society should be strengthened.

Objective

To evaluate the preliminary effects of a WeChat‐based educational intervention on the social participation of community‐dwelling older adults in China.

Methods

This study was a quasi‐experimental design. Twenty‐eight community‐dwelling older adults participated in a WeChat‐based educational intervention. The intervention contents included concepts and preparation of social participation, analysis of participation resources and capabilities, technological adaptation, emotional management, setting of to‐do lists, etc. Social participation, self‐worth and subjective well‐being were measured via the WeChat application on smartphones at baseline, immediately after the intervention, and a 3‐month follow‐up. We analysed data using paired t‐tests and analysis of variance (ANOVA).

Results

We found statistically significant improvements in social participation (active aging) (F = 4.408; p < .05) as well as the self‐worth dimensions of moral worth (F = 4.135; p < .05) and psychological worth (F = 3.234; p < .05), and the negative‐affect dimension of subjective well‐being being decreased (F = 2.484; p < .05).

Conclusions

The WeChat‐based education intervention can effectively improve social participation and self‐worth, and may provide effective preventive healthcare solutions for older adults in China.

Implications for Practice

The enormous value of the social participation of independent older adults must be recognised. Nurses can use smartphones to deliver health and social participation information in routine programs in aged care.
Disrupted‐in‐schizophrenia 1 protein aggregates in cerebrospinal fluid are elevated in patients with first‐episode psychosis
Authors: Pils Marlene , Rutsch Julia , Eren Feride , Engberg Göran , Piehl Fredrik , Cervenka Simon , Sellgren Carl , Troßbach Svenja , Willbold Dieter , Erhardt Sophie , Bannach Oliver , Korth Carsten
Published: September 2023

Aim

The disrupted‐in‐schizophrenia 1 (DISC1) protein is a key regulator at the intersection of major signaling pathways relevant for adaptive behavior. It is prone to posttranslational changes such as misassembly and aggregation but the significance of such transformations for human mental illness has remained unclear. We aimed to demonstrate the occurrence of DISC1 protein aggregates in patients with first‐episode psychosis (FEP).

Method

Cerebrospinal fluid samples of patients with FEP (n = 50) and matched healthy controls (HCs; n = 47) were measured by the highly sensitive surface‐based fluorescence intensity distribution analysis technology that enables single aggregate detection.

Results

We demonstrate that DISC1 protein aggregates are increased in cerebrospinal fluid samples of patients with FEP versus HCs. The concentration was in the low femtomolar range. No correlations were found with specific symptom levels, but the difference was particularly significant in the subset of patients with the diagnoses schizophrenia, unspecified (DSM‐IV 295.9) or schizoaffective disorder (DSM‐IV 295.70) at 18‐month follow‐up. DISC1 protein aggregate levels did not significantly change within the 18‐month observation interval and were on average higher for individuals carrying the major DISC1 rs821577 allele, before correction.

Conclusion

The occurrence of protein aggregates in vivo in patients with psychotic disorders has not been previously reported. It underscores the significance of posttranslational modifications of proteins both as pathogenetic mechanisms and as potential diagnostic markers in these disorders.
Xeroderma pigmentosum group G with pellagroid rash: A rare presentation
Authors: Garg Sonika , Garg Kunal , Thakur Vishal , Behera Biswanath
Published: September 2023

Xeroderma pigmentosum (XP), a heterogeneous genodermatoses, has a variable clinical spectrum ranging from mild freckling and photosensitivity to severe skeletal and neurological abnormalities and cutaneous malignancies. Herein, we present the case of a 4‐year‐old boy with XP group G who presented with a pellagroid rash.
Perceptions of skincare ingredients and product labels in pediatric eczema care
Authors: Zemlok Sarah Kamsiah , Bentivegna Kathryn , Torre Kristin , Rothe Marti , Chang Mary Wu
Published: September 2023

Educating pediatric eczema patients and caregivers on appropriate product selection and avoidance of common irritants or allergens is a crucial aspect of eczema management. This study surveyed 80 pediatric caregivers in an academic pediatric dermatology clinic to assess influential factors in caregivers' selection of pediatric eczema‐care products and identify ways to improve patient counseling on appropriate product selection and avoidance of common irritants or allergens. Caregivers frequently reported positive perceptions of commonly recommended ingredients for eczema but had inconsistent perceptions of fragrant plant oils and extracts, regardless of previous counseling on fragrance avoidance. These findings demonstrate uncertainty and misperceptions perpetuated by product labeling and a need for improved counseling strategies for avoiding fragrance and excessive product costs.
The dose response of erythemal area and intensity on the unprotected skin fits well to a logistic 3P model in SPF tests of a Chinese population, which has the potential to improve the precision and consistency of minimal erythema dose determination
Authors: Qu Di , Liao Feng , Liu Jianwei , Li Xiangzi , Ye Congxiu , Zheng Yue , Xie Xiaoyuan , Yi Jinling , Lai Wei
Published: September 2023

Background

The current ISO guidelines for minimal erythema dose (MED) determination require assessment of erythema area of UV‐irradiated skin sites. However, this parameter has not been adequately quantified in daily practice. The aims of this study were to investigate the dose response on the unprotected skin sites by quantifying the erythema area and intensity and to show the potential for improving the precision and consistency of MEDu determination by developing predictive models.

Methods

Standard radiation tests were conducted on the back of 31 healthy Chinese volunteers and the MEDu site of each subject was clinically determined by dermatologists. Images of test sites were captured 24 h after radiation, and the erythema area (%EA) and intensity (∆a*) were measured by image analysis. The data were fitted to a logistic 3P function to obtain dose–response curves, and a set of logit (inverse‐logistic) models were then derived. An erythema area threshold of %EA = 52% was established to predict MEDu based on the clinical endpoints defined by ISO 24444:2019.

Results

Analysis of the clinically determined MEDu sites revealed wide ranges of %EA (62.3 ± 15% SD) and ∆a* (2.96 ± 0.92 SD). The dose response fitted well to a logistic 3P model (mean R2 = 0.965 and 0.975 for %EA and ∆a*, respectively). Applying the area threshold, values of MEDu were determined by the logit model for the test population, which significantly improved the consistency of MEDu determination (52 ± 0% SD and 2.73 ± 0.61 SD for %EA and ∆a*, respectively).

Conclusion

This study demonstrated that the dose response of UV‐induced erythema can be quantified and modeled once the erythema area and intensity are measured. The results of this study show the potential to improve the precision and consistency of MEDu determination in an SPF test. The similar potential in photodermatological, therapeutic, and diagnostic applications was also implied.
The role of data‐based intelligence and experience on time efficiency of taxi drivers: An empirical investigation using large‐scale sensor data
Authors: Lu Yingda , Wang Youwei , Chen Yuxin , Xiong Yun
Published: September 2023

In this paper, we employ large‐scale sensor data to examine the impact of data‐based intelligence and work‐related experience on the time efficiency of individual taxi drivers, measured by their propensity of choosing the fastest routes. The identification strategy is built on (1) a unique exogenous policy shock‐banning taxi‐hailing app with an embedded GPS system, and (2) a measure of nonrecurring congestion avoidance, enabled by the real‐time sensor data, which serves as a proxy for GPS usage. Our empirical model provides evidence that data‐based intelligence improves taxi drivers’ routing decisions by close to 3% as measured by trip speed. Our results further demonstrate that inexperienced drivers have a higher chance of choosing the fastest route, as they are more likely to rely on the real‐time traffic information from GPS technology than experienced drivers. The general implications of our findings on the adoption and utilization of data‐based performance‐enhancing technology are discussed in closing.
Normal congruency sequence effects in psychopathology: A behavioral and electrophysiological examination using a confound‐minimized design
Authors: Clayson Peter E. , Shuford John L. , Rast Philippe , Baldwin Scott A. , Weissman Daniel H. , Larson Michael J.
Published: September 2023

Clinical studies of adaptive control emphasize the role disruptions in control play in psychopathology. However, many studies used confound‐laden designs and examined only one type of psychopathology. Recent studies of event‐related potentials (ERPs) suggest that robust congruency sequence effects (CSEs)—a popular index of adaptive control—appear in confound‐minimized designs. Thus, the present study sought to determine whether a confound‐minimized CSE paradigm could identify adaptive control dysfunction in people with major depressive disorder (MDD), generalized anxiety disorder (GAD), and obsessive‐compulsive disorder (OCD). We predicted that participants with MDD and GAD would show smaller ERP CSEs and that participants with OCD would show larger ERP CSEs than healthy controls. Data from 44 people with GAD, 51 people with MDD, 31 people with OCD, and 56 healthy comparison participants revealed normal CSEs as indexed by response times (RTs) and ERPs in the psychopathology groups. Moreover, psychiatric symptoms did not moderate these CSEs. Finally, we observed a strong mean–variance relationship in RT CSEs, such that participants with stronger post‐recruitment of control in mean RT scores showed the most consistent post‐conflict responses (i.e., the least intraindividual variability). These findings suggest that prior findings from confound‐laden tasks indicating altered CSEs in psychopathology stem from processes that are unrelated to adaptive control. Future research should employ experimental designs that isolate these processes to advance our understanding of abnormal CSEs in psychopathology.
Testosterone supplementation improves estrogen synthesis of buffalo (Bubalus bubalis) granulosa cells
Authors: Zhang Jun , Sun Junming , Xiao Linlin , Ouyang Yiqiang , Shi Deshun , Lu Fenghua
Published: September 2023

Granulosa cells (GCs) synthesize estrogens needed for follicular growth. However, the effects of androgen on estrogen production in buffalo GCs remain unclear. In this study, the impacts of testosterone on estrogen synthesis in buffalo GCs were examined. The results showed that testosterone that was added to cell medium at a concentration of 10−7 mol/L and applied to GCs for 48 or 72 h enhanced the estrogen synthesis of buffalo GCs. This study provides a theoretical basis for further exploration of ovarian endocrine mechanism for steroidogenesis.
Experimental manipulation of uncanny feeling does not increase adherence to conspiracy theories
Authors: Varet Florent , Adam‐Troian Jaïs , Bonetto Eric , Akinyemi Alexis , Lantian Anthony , Voisin Dimitri , Delouvée Sylvain
Published: September 2023

Research over the past decade has shown that endorsement of conspiracy theories (CTs) is shaped by motivated cognition processes. Accordingly, CTs are theorized to stem from compensatory processes, as individuals attempt to cope with existential threats (i.e., uncertainty, loss of control). Based on the meaning maintenance model, we investigated whether this compensatory effect could follow from epistemic threats in domains unrelated to CTs in the form of uncanniness. Feelings of uncanniness were experimentally manipulated through exposure to absurdist art and literature in a set of five studies, followed by a mini meta‐analysis (Ntotal = 1,041). We conducted a final, preregistered sixth study (N = 266) manipulating uncanniness through autobiographical recall. No robust evidence for a compensatory effect was found. We discussed methodological and conceptual limitations of the meaning maintenance model, as well as boundary conditions under which conspiracy theories could have a compensatory function to deal with threats.
Quantifying demands on the hamstrings during high‐speed running: A systematic review and meta‐analysis
Authors: McNally Timothy , Edwards Suzi , Halaki Mark , O'Dwyer Nicholas , Pizzari Tania , Blyton Sarah
Published: September 2023

Introduction

Hamstring strain injury (HSI) remains a performance, economic, and player availability burden in sport. High‐speed running (HSR) is cited as a common mechanism for HSI. While evidence exists regarding the high physical demands on the hamstring muscles in HSR, meta‐analytical synthesis of related activation and kinetic variables is lacking.

Methods

A systematic search of Medline, Embase, Scopus, CINAHL, SportDiscus, and Cochrane library databases was conducted in accordance with the PRISMA 2020 guidelines. Studies reporting hamstring activation (electromyographic [EMG]) or hamstring muscle/related joint kinetics were included where healthy adult participants ran at or beyond 60% of maximum speed (activation studies) or 4 m per second (m/s) (kinetic studies).

Results

A total of 96 studies met the inclusion criteria. Run intensities were categorized as “slow,” “moderate,” or “fast” in both activation and kinetic based studies with appropriate relative, and raw measures, respectively. Meta‐analysis revealed pooled mean lateral hamstring muscle activation levels of 108.1% (95% CI: 84.4%–131.7%) of maximal voluntary isometric contraction (MVIC) during “fast” running. Meta‐analysis found swing phase peak knee flexion internal moment and power at 2.2 Newton meters/kilogram (Nm/kg) (95% CI: 1.9–2.5) and 40.3 Watts/kilogram (W/kg) (95% CI: 31.4–49.2), respectively. Hip extension peak moment and power was estimated as 4.8 Nm/kg (95% CI: 3.9–5.7) and 33.1 W/kg (95% CI: 17.4–48.9), respectively.

Conclusions

As run intensity/speed increases, so do the activation and kinetic demands on the hamstrings. The presented data will enable clinicians to incorporate more objective measures into the design of injury prevention and return‐to‐play decision‐making strategies.
Transfusion of red blood cells in venoarterial extracorporeal membrane oxygenation: A multicenter retrospective observational cohort study
Authors: Raasveld Senta Jorinde , Karami Mina , Schenk Jimmy , Dos Reis Miranda Dinis , Mandigers Loes , Dauwe Dieter F. , De Troy Erwin , Pappalardo Federico , Fominskiy Evgeny , van den Bergh Walter M. , Oude Lansink‐Hartgring Annemieke , van der Velde Franciska , Maas Jacinta J. , van de Berg Pablo , de Haan Maarten , Donker Dirk W. , Meuwese Christiaan L. , Taccone Fabio Silvio , Peluso Lorenzo , Lorusso Roberto , Delnoij Thijs S. R. , Scholten Erik , Overmars Martijn , Ivančan Višnja , Bojčić Robert , de Metz Jesse , van den Bogaard Bas , de Bakker Martin , Reddi Benjamin , Hermans Greet , Broman Lars Mikael , Henriques José P. S. , Vlaar Alexander P. J.
Published: September 2023

Background

Evidence‐based recommendations for transfusion in patients with venoarterial extracorporeal membrane oxygenation (VA ECMO) are scarce. The current literature is limited to single‐center studies with small sample sizes, therefore complicating generalizability. This study aims to create an overview of red blood cell (RBC) transfusion in VA ECMO patients.

Methods

This international mixed‐method study combined a survey with a retrospective observational study in 16 centers. The survey inventoried local transfusion guidelines. Additionally, retrospective data of all adult patients with a VA ECMO run >24 h (January 2018 until July 2019) was collected of patient, ECMO, outcome, and daily transfusion parameters. All patients that received VA ECMO for primary cardiac support were included, including surgical (i.e., post‐cardiotomy) and non‐surgical (i.e., myocardial infarction) indications. The primary outcome was the number of RBC transfusions per day and in total. Univariable logistic regressions and a generalized linear mixed model (GLMM) were performed to assess factors associated with RBC transfusion.

Results

Out of 419 patients, 374 (89%) received one or more RBC transfusions. During a median ECMO run of 5 days (1st–3rd quartile 3–8), patients received a median total of eight RBC units (1st–3rd quartile 3–17). A lower hemoglobin (Hb) prior to ECMO, longer ECMO‐run duration, and hemorrhage were associated with RBC transfusion. After correcting for duration and hemorrhage using a GLMM, a different transfusion trend was found among the regimens. No unadjusted differences were found in overall survival between either transfusion status or the different regimens, which remained after adjustment for potential confounders.

Conclusion

RBC transfusion in patients on VA ECMO is very common. The sum of RBC transfusions increases rapidly after ECMO initiation, and is dependent on the Hb threshold applied. This study supports the rationale for prospective studies focusing on indications and thresholds for RBC transfusion.
The effect of increased collect pump rate on collection efficiency in hematopoietic progenitor cell collection by apheresis in allogeneic adult donors—A single center analysis
Authors: Miller Anthony , Davies Jeramy , Young Kathryn , Eckman Emily , Lo Melissa Y. , Erskine Hannah , Knutson Lisa , Ondricek Sara , Margolis Jamie M. , Auletta Jeffery J. , Miller John P. , Stefanski Heather E. , Devine Steven , Pham Huy P.
Published: September 2023

Background

Optimizing CD34 recovery while minimizing harm to hematopoietic progenitor cell donors by apheresis (HPC(A) donors) is critical to the success of allogeneic hematopoietic cell transplantation. We examined the efficacy and safety of starting allogeneic HPC(A) donors at a collect pump rate (CPR) of 2 mL/min on the Spectra Optia regardless of the inlet flow rate and/or pre‐apheresis white blood cell (WBC) count (high CPR group).

Study Design and Methods

A single‐center retrospective study was performed on allogeneic adult donors from 10/2020 to 12/2022. From 10/2020 to 6/19/2022, all donors had CPR of ~1 mL/min (historical group). High CPR group started 6/20/2022.

Results

During the study period, 412 donors were in historical group versus 196 (32.2%) in high CPR group. Median CD34 collection efficiency (CE) was higher and more consistent in high CPR group (55.1% vs. 53% in historical group, p < .0001) and remained significant in multivariate analysis. Although product volume was higher in high CPR group, WBC, hematocrit, and platelet concentrations were significantly lower. No difference in engraftment outcomes in patients receiving products from two groups was observed. Moreover, no differences occurred in a significant peri‐procedural adverse event or percent decrease in platelets (6.87% decrease in platelets per 100 × 106 CD34 cells collected versus 6.66% in historical group, p = .89). Furthermore, high CPR group had ~26 min less in collection time for every 100 × 106 CD34 cells collected, resulting in less positive fluid balances.

Conclusions

Starting allogeneic HPC(A) donor collection at a CPR of 2 mL/min is safe and effective.
A small cusped hyperbolic 4‐manifold
Authors: Riolo Stefano
Published: September 2023

By gluing some copies of a polytope of Kerckhoff and Storm's, we build the smallest known orientable hyperbolic 4‐manifold that is not commensurable with the ideal 24‐cell or the ideal rectified simplex. It is cusped and arithmetic, and has twice the minimal volume.
Equivariant knots and knot Floer homology
Authors: Dai Irving , Mallick Abhishek , Stoffregen Matthew
Published: September 2023

We define several equivariant concordance invariants using knot Floer homology. We show that our invariants provide a lower bound for the equivariant slice genus and use this to give a family of strongly invertible slice knots whose equivariant slice genus grows arbitrarily large, answering a question of Boyle and Issa. We also apply our formalism to several seemingly nonequivariant questions. In particular, we show that knot Floer homology can be used to detect exotic pairs of slice disks, recovering an example due to Hayden, and extend a result due to Miller and Powell regarding stabilization distance. Our formalism suggests a possible route toward establishing the noncommutativity of the equivariant concordance group.
Competition between ion beam sputtering and self-organization of point defects for surface nanostructuring on germanium
Authors: Oishi Naoto , Yasuoka Tatsuya , Kawaharamura Toshiyuki , Nitta Noriko
Published: September 2023

Nanostructuring via ion beam irradiation on Ge substrates can be activated by ion beam sputtering and self-organization of point defects (SPDs). For evaluating the mechanism by which these formation factors compete, we studied nanostructuring on Ge substrates subjected to sputtering-dominant conditions, viz., the low-energy ion incidence. A focused ion beam was used for nanostructuring and adjusting an angle of ion incidence to the surface normal range of 0°–60°. The ions accelerated for irradiation were Ga+ with an incident energy of 5–30 keV, and the fluence and beam current were 1 × 1020–1 × 1022 ions/m2 and 0.5–16.7 nA, respectively. Based on the results of serial experiments, the incident energy of 5 keV can be the threshold for the activation of nanostructuring by SPD.
Microstructure, creep properties, and electrical resistivity of magnetron sputtering deposited SAC305 thin films
Authors: Ojha Manish , Mohammed Yousuf , Stone D. S. , Elmustafa A. A.
Published: September 2023

This paper investigates the surface morphology, mechanical properties, and electrical resistivity of 96.5Sn–3.0Ag–0.5Cu (SAC305) thin films deposited on Si and SiO2 substrates through RF magnetron sputtering. Various deposition parameters were tested using both DC and RF power sources at different pressures and powers to produce robust continuous films. The most optimal surface morphology, with an average grain size of ∼1 μm and a thickness of ∼2.2 μm, was accomplished at a pressure of 2.4 mTorr and 200 W power. After polishing, a uniform thickness of 1800 nm with a mean roughness (Ra) of 14.9 nm was obtained. The samples contained polycrystalline β-Sn grains at (200) diffraction planes with a preferred orientation 2θ of 30.70°. Although the XRD pattern did not indicate any Ag peaks, weak peaks of Ag3Sn were observed at 2θ of 37.60° and 39.59°, corresponding to diffraction planes (020) and (211), respectively. The electrical resistivity of the SAC305 thin film deposited on the SiO2 substrate and of the bulk SAC305 samples were measured as 19.6 and 13.7 μΩ cm, respectively. It was noted that changes in hold time at peak loads or the rate of loading in the creep experiments did not significantly influence the creep properties of the SAC305 bulk or thin film material.
Exploring the limits of virtual source localization with amplitude panning on a flat panel with actuator array: Implications for future research
Authors: Yu Ziying , Zhu Qiaoxi , Wu Ming , Yang Jun
Published: September 2023

Immersive and spatial sound reproduction has been widely studied using loudspeaker arrays. However, flat-panel loudspeakers that utilize thin flat panels with force actuators are a promising alternative to traditional coaxial loudspeakers for practical applications, with benefits in low-visual profiles and diffuse radiation. Literature has addressed the sound quality and applications of flat-panel loudspeakers in three-dimensional sound reproduction, such as wave field synthesis and sound zones. This paper revisits the spatial sound perception of flat-panel loudspeakers, specifically the localization mismatch between the perceived and desired sound directions when using amplitude panning. Subjective tests in an anechoic chamber with 24 subjects result in the mean azimuth direction mismatch within ±6.0° and the mean elevation mismatch within ±10.0°. The experimental results show that the virtual source created by amplitude panning over a flat-panel loudspeaker still achieves spatial localization accuracy close to that of a real sound source, despite not using complex algorithms or acoustic transfer function information. The findings of this study establish a benchmark for virtual source localization in spatial sound reproduction using flat-panel loudspeakers, which can serve as a starting point for future research and optimization of algorithms.
Impact of acquired broad-spectrum β-lactamases on susceptibility to oral penems/carbapenems (tebipenem, sulopenem, and faropenem) alone or in combination with avibactam and taniborbactam β-lactamase inhibitors in
Escherichia coli
Authors: Le Terrier Christophe , Nordmann Patrice , Bouvier Maxime , Poirel Laurent
Published: September 2023

The impact of β-lactamases on susceptibility to oral penems/carbapenems (tebipenem, sulopenem, and faropenem) and other carbapenem molecules was evaluated in
Escherichia coli
, alone and in combination with avibactam or taniborbactam β-lactamase inhibitors. Tebipenem and sulopenem exhibited a similar spectrum of activity compared to the intravenous carbapenems and displayed lower MIC values than ceftibuten-avibactam against
E. coli
producing extended-spectrum β-lactamases or AmpC enzymes. Combined with taniborbactam, tebipenem and sulopenem exhibited low MIC values against almost all tested recombinant
E. coli
, including metallo-β-lactamase producers.
Complete genome sequence of
Butyricimonas faecihominis
JCM 18676
T
Authors: Fukuoka Hironori , Tourlousse Dieter M. , Hamajima Mayu , Koike Kazuyoshi , Endo Itaru , Sekiguchi Yuji
Published: September 2023

We report a complete genome sequence of
Butyricimonas faecihominis
JCM 18676
T
, generated by nanopore sequencing. The genome consists of a single circular chromosome of 4,851,806 bp, with a G + C content of 42.9%, and was predicted to contain 15 rRNA and 61 tRNA genes and encode for 3,946 proteins.
Zinc excess impairs
Mycobacterium bovis
growth through triggering a Zur-IdeR-iron homeostasis signal pathway
Authors: Li Xiaohui , Chen Liu , Wang Yuankun , Guo Xiao , He Zheng-Guo
Published: September 2023

Zinc excess is toxic to bacteria and, thus, represents an important innate defense mechanism of host cells, especially against mycobacterial infections. However, the signaling pathway triggered by zinc excess and its relationship with iron homeostasis remain poorly understood in mycobacteria. Here, we characterize a novel Zur-IdeR-iron homeostasis signaling pathway that modulates the growth of
Mycobacterium bovis
under zinc toxicity. We found that the regulator Zur interacts with the iron-homeostasis regulator IdeR, enhancing the DNA-binding ability of IdeR. Excess zinc disrupts this interaction and represses
ideR
transcription through Zur, which promotes the expression of iron uptake genes and leads to the accumulation of intracellular iron in
M. bovis
. The elevated iron levels lower the bacterial survival ability under excess zinc stress. Consistently, deleting
zur
hinders intracellular iron accumulation of
M. bovis
and enhances bacterial growth under stress, while silencing
ideR
impairs the growth of the wild-type and
zur
-deleted strains under the same conditions. Interestingly, both Zur and IdeR are conserved in bacteria facing zinc toxicity. Overall, our work uncovers a novel antimicrobial signal pathway whereby zinc excess disrupts iron homeostasis, which may deepen our understanding of the crosstalk mechanism between iron and zinc homeostasis in bacteria.

IMPORTANCE

As a catalytic and structural cofactor of proteins, zinc is essential for almost all living organisms. However, zinc excess is toxic and represents a vital innate immunity strategy of macrophages to combat intracellular pathogens, especially against mycobacterial pathogens such as
Mycobacterium tuberculosis
, the causative agent of tuberculosis. Here, we first characterize an antibacterial signaling pathway of zinc excess and its relationship with iron homeostasis in
M. bovis
. We found that excess zinc inhibits the transcription of
ideR
and its DNA-binding activity through Zur, which, in turn, promotes the expression of iron uptake genes, causes intracellular iron accumulation, and finally impairs the bacterial growth. This study reveals the existence of the Zur-IdeR-iron homeostasis pathway triggered by zinc excess in
M. bovis
, which will shed light on the crosstalk mechanisms between zinc and iron homeostasis in bacteria and the antimicrobial mechanisms of host-mediated zinc toxicity.
Listeria monocytogenes
GshF contributes to oxidative stress tolerance via regulation of the phosphoenolpyruvate-carbohydrate phosphotransferase system
Authors: Chen Mianmian , Zhang Jiaxue , Xia Jing , Sun Jing , Zhang Xian , Xu Jiali , Deng Simin , Han Yue , Jiang Lingli , Song Houhui , Cheng Changyong
Published: September 2023

Glutathione (GSH) is an essential component of the glutaredoxin (Grx) system, and it is synthesized by the enzyme glutathione synthase GshF in
Listeria monocytogenes
. GSH plays a crucial role in regulating
Listeria
virulence by modifying the virulence factors LLO and PrfA. In this study, we investigated the involvement of
L. monocytogenes
GshF in oxidative tolerance and intracellular infection. Our findings revealed that the deletion of
gshF
resulted in a significant reduction in bacterial growth
in vitro
when exposed to diamide and copper ions stress. More importantly, this deletion also impaired the efficiency of invasion and proliferation in macrophages and mice organs. Furthermore, GshF influenced global transcriptional profiles, including carbohydrate and amino acid metabolism, particularly those related to the phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS) genes
lmo1997-lmo2004
, under oxidative stress conditions. In the wild-type strain, the transcription of
lmo1997-lmo2004
was notably downregulated in response to copper ions and diamide stress compared to normal conditions. However, in the absence of
gshF
, the transcripts of
lmo1997-lmo2004
were upregulated in response to these stress conditions. Notably, the deletion of

iiB
man

(
lmo2002
) enhanced oxidative stress tolerance to copper ions, whereas overexpression of

iiB
man

reduced this resistance. In conclusion, our study provides the first evidence that
L. monocytogenes
GshF plays a crucial role in bacterial antioxidation through the regulation of

iiB
man

.

IMPORTANCE

Listeria monocytogenes
has developed various mechanisms to withstand oxidative stress, including the thioredoxin and glutaredoxin systems. However, the specific role of the glutathione synthase GshF, responsible for synthesizing GSH in
L. monocytogenes
, in oxidative tolerance remains unclear. This study aimed to elucidate the relationship between GshF and oxidative tolerance in
L. monocytogenes
by examining the efficiency of invasion and proliferation in macrophages and mice organs, as well as analyzing global transcriptional profiles under oxidative stress conditions. The results revealed that GshF plays a significant role in
L. monocytogenes
’ response to oxidative stress. Notably, GshF acts to suppress the transcription of phosphoenolpyruvate-carbohydrate phosphotransferase system genes
lmo1997-lmo2004
, among which

iiB
man

(
lmo2002
) was identified as the most critical gene for resisting oxidative stress. These findings enhance our understanding of how
L. monocytogenes
adapts to its environment and provide valuable insights for investigating the environmental adaptation mechanisms of other pathogenic bacteria.
Evolution and distribution of rabies viruses from a panorama view
Authors: Li Gen , Zhang Yue , He Hong-Ling , Chen Chang-Yi , Li Xin , Xiao Yu , Yan Zhi-Bin , Chu Ying , Luo Jun , Guo Xiao-Feng
Published: September 2023

Rabies kills more than 59,000 people annually, mainly in developing countries. Previous studies on the evolution and distribution of rabies viruses (RABVs) were scattered. Here, we explore the evolution and distribution of this deadly virus from a novel panorama view. Multiple bioinformatic software tools were employed to analyze the phylogenetic diversity, evolution, spatiotemporal, and distribution of RABVs. The analyses were based on 1,202 qualified full-length genomes of RABVs and numerous literatures. Of the 10 distinct phylogenetic clades of RABV that we identified, more frequent intra- and inter-clade recombination occurs in the sequences of Asian-SEA, Arctic, and Cosmopolitan clades isolated from China, while according to existing sequence information, RABV might originate from bats (posterior probability, PP = 0.75, PP = 0.60 inferred from N and L genes, separately) in North America (PP = 0.57, PP = 0.62 inferred from N and L genes, separately). Due to the difference in evolutionary rate of N (2.22 × 10
−4
subs/site/year, 95% HPD 1.99–2.47 × 10
−4
subs/site/year) and L genes (1.67 × 10
−4
subs/site/year, 95% HPD 1.59–1.74 × 10
−4
subs/site/year), the root age was 1,406.6 (95% HPD 1,291.2–1,518.2) and 1,122.7 (95% HPD 1,052.4–1,193.9) inferred from N and L genes, separately. Among other findings, Mephitidae plays an important role in the interspecific transmission and communication of RABV, which we found tends to spread to populations genetically proximate to the host. We also identified amino acids under positive selection in different genes of different clades as well as single nucleotide variation sites important for different lineages.

IMPORTANCE

Rabies virus is widely distributed all over the world, and wild animals are its largest potential reservoir. Our study offers a panorama view about evolution and distribution of rabies viruses and emphasizes the need to monitor the transmission dynamics of animal rabies.
Sacral stress fracture in a young-adult, long-distance runner: an underestimated cause of low back pain
Authors: Pinheiro Joana Páscoa , Rovisco Branquinho Lurdes , Pinheiro João
Published: September 2023

Sacral stress fractures (SSFs) in physically active young patients are frequently misdiagnosed due to the lack of specificity of signs and symptoms. Over the last years, these injuries have been described as rare, although some studies report that the incidence of an SSF in athletes may be as high as 20%.

We describe a case of a male long-distance runner in his late 20s with a 1-month undiagnosed SSF. The patient complaints included insidious right low back and buttock pain without trauma that started after running a marathon. MRI revealed an extensive area of bone marrow oedema in the right sacral ala consistent with an SSF.

This case highlights the importance of investigating SSF in young-athlete patients who were otherwise healthy, using appropriate imaging modalities to assess the presence and morphology of a fracture.
Fine visuomotor skills in amblyopia: a systematic review and meta-analysis
Authors: Rakshit Archayeeta , Schmid Katrina L , Webber Ann L
Published: September 2023

Background

Amblyopia is characterised by reduced visual acuity, poor binocular sensory fusion, and impaired or absent stereoacuity. Understanding the extent to which amblyopia affects everyday task performance is important to quantifying the disease burden of amblyopia and can assist clinicians to understand patients’ likely functional capability.

Methods

A systematic literature search identified published studies comparing fine visuomotor performance in either children or adults with amblyopia and those with normal binocular vision. The included studies (22 studies involving 835 amblyopes and 561 controls) reported results of self-perception patient reported outcome measures, tests of motor proficiency and video recorded reaching and grasping. The outcomes of 17 studies were grouped into four meta-analyses, with pooled results reported as standardised mean difference (SMD) with corresponding 95% CI.

Results

Regardless of the cause of amblyopia (anisometropia, strabismus, mixed, deprivation), significant reduction in self-perception of physical competence and athletic competence (SMD=−0.74, 95% CI −1.23 to −0.25, p=0.003); fine motor skills scores (SMD=−0.86, 95% CI −1.27 to −0.45, p<0.0001); speed of visually guided reaching and grasping movements (SMD=0.86, 95% CI 0.65 to 1.08, p<0.00001); and precision of temporal eye-hand coordination (SMD=0.75, 95% CI 0.26 to 1.25, p=0.003) occurred in amblyopes compared with those with normal visual development.

Conclusion

Reports of the impact of amblyopia on fine motor skills performance find poorer outcomes in participants with amblyopia compared with those with normal vision development. Consistency in the outcome measure used to assess the functional impact of amblyopia would be valuable for future studies.
Negotiating public-health intellectual property licensing agreements to increase access to health technologies: an insider’s story
Authors: Gore Charles , Morin Sébastien , Røttingen John-Arne , Kieny Marie Paule
Published: September 2023

Public health voluntary licensing of intellectual property has successfully been applied to increase access to medicines in certain disease areas, producing health benefits and economic savings, particularly in low-income and middle-income countries. There is however limited understanding of the intricacies of the approach, the modalities by which it works in practice, its levers and the trade-offs made. Such knowledge may be critical in deciding what role licensing should have in pandemic preparedness and equitable access to health technologies more broadly. This paper examines the case for licensing, the considerations for balancing public health needs, the challenges of negotiations, and the processes for validating proposed agreements. No access mechanism is perfect, but evidence suggests that public-health licensing has an important role to play, although it remains underused. Understanding some of the realities, strengths, limitations and complexities of applying the model may help calibrate expectations and develop incentives to expand its applications.
LAparoscopic Versus Abdominal hysterectomy (LAVA): protocol of a randomised controlled trial
Authors: Antoun Lina , Middleton Lee , Smith Paul , Saridogan Ertan , Cooper Kevin , Brocklehurst Peter , McKinnon William , Bevan Sheriden , Woolley Rebecca , Jones Laura , Fullard Jayne , Morgan Monique , Roberts Tracy , Clark T Justin
Published: September 2023

Introduction

There is uncertainty about the advantages and disadvantages of laparoscopic hysterectomy compared with abdominal hysterectomy, particularly the relative rate of complications of the two procedures. While uptake of laparoscopic hysterectomy has been slow, the situation is changing with greater familiarity, better training, better equipment and increased proficiency in the technique. Thus, a large, robust, multicentre randomised controlled trial (RCT) is needed to compare contemporary laparoscopic hysterectomy with abdominal hysterectomy to determine the safest and most cost-effective technique.

Methods and analysis

A parallel, open, non-inferiority, multicentre, randomised controlled, expertise-based surgery trial with integrated health economic evaluation and an internal pilot with an embedded qualitative process evaluation. A within trial-based economic evaluation will explore the cost-effectiveness of laparoscopic hysterectomy compared with open abdominal hysterectomy. We will aim to recruit 3250 women requiring a hysterectomy for a benign gynaecological condition and who were suitable for either laparoscopic or open techniques. The primary outcome is major complications up to six completed weeks postsurgery and the key secondary outcome is time from surgery to resumption of usual activities using the personalised Patient-Reported Outcomes Measurement Information System Physical Function questionnaire. The principal outcome for the economic evaluation is to be cost per QALY at 12 months’ postsurgery. A secondary analysis is to be undertaken to generate costs per major surgical complication avoided and costs per return to normal activities.

Ethics and dissemination

The study was approved by the West Midlands-Edgbaston Research Ethics Committee, 18 February 2021 (Ethics ref: 21/WM/0019). REC approval for the protocol version 2.0 dated 2 February 2021 was issued on 18 February 2021.

We will present the findings in national and international conferences. We will also aim to publish the findings in high impact peer-reviewed journals. We will disseminate the completed paper to the Department of Health, the Scientific Advisory Committees of the RCOG, the Royal College of Nurses (RCN) and the BSGE.

Trial registration number

ISRCTN14566195.
Development and validation of a multimodal feature fusion prognostic model for lumbar degenerative disease based on machine learning: a study protocol
Authors: Wang Zhipeng , Zhao Xiyun , Li Yuanzhen , Zhang Hongwei , Qin Daping , Qi Xin , Chen Yixin , Zhang Xiaogang
Published: September 2023

Introduction

Lumbar degenerative disease (LDD) is one of the most common reasons for patients to present with low back pain. Proper evaluation and treatment of patients with LDD are important, which clinicians perform using a variety of predictors for guidance in choosing the most appropriate treatment. Because evidence on which treatment is best for LDD is limited, the purpose of this study is to establish a clinical prediction model based on machine learning (ML) to accurately predict outcomes of patients with LDDs in the early stages by their clinical characteristics and imaging changes.

Methods and analysis

In this study, we develop and validate a clinical prognostic model to determine whether patients will experience complications within 6 months after percutaneous endoscopic lumbar discectomy (PELD). Baseline data will be collected from patients’ electronic medical records. As of now, we have recruited a total of 580 participants (n=400 for development, n=180 for validation). The study’s primary outcome will be the incidence of complications within 6 months after PELD. We will use an ML algorithm and a multiple logistic regression analysis model to screen factors affecting surgical efficacy. We will evaluate the calibration and differentiation performance of the model by the area under the curve. Sensitivity (Sen), specificity, positive predictive value and negative predictive value will be reported in the validation data set, with a target of 80% Sen. The results of this study could better illustrate the performance of the clinical prediction model, ultimately helping both clinicians and patients.

Ethics and dissemination

Ethical approval was obtained from the medical ethics committee of the Affiliated Hospital of Gansu University of Traditional Chinese Medicine (Lanzhou, China; No. 2022-57). Findings and related data will be disseminated in peer-reviewed journals, at conferences, and through open scientific frameworks.

Trial registration number

Chinese Clinical Trial Register (www.chictr.org.cn) No. ChiCTR2200064421.