bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Community‐to‐Hospital Specialist Otology Pathway Using Telemedicine: A Pilot Study of 50 Patients
Authors: Patel Ankit , Forde Cillian , Doal Suneal , Patel Jay , Clare Dawn , Burslem Michael , Manjaly Joseph G. , Mehta Nishchay
Published: June 2024

Introduction

Pathway innovation using smartphone otoscopy and tablet‐based audiometry technologies to deliver ear and hearing services via trained audiologists may improve efficiency of the service. An ENT‐integrated‐community‐ear service (ENTICES—combining community audiology management, remote ENT review and novel technologies) was piloted. We aimed to assess the efficiency and safety of ENTICES.

Method

ENTICES was a community‐based and audiologist‐led pathway. Patients with otological symptoms were self‐referred to this service. Smartphone otoscopy and tablet‐based audiograms were performed. Two otologists reviewed all decisions made in the community by audiologists based on video‐otoscopy, hearing tests and chart reviews. Data on the first 50 consecutive new patients attending either consultant‐led hospital otology clinics (HOC), audiologist‐led hospital advanced audiology diagnostics (AAD) or ENTICES clinics were collected between 1 August 2021 and 31 December 2021. Data were collected through chart reviews and questionnaires to compare the three pathways with respect to efficiency, patient satisfaction, technology utility and safety.

Results

No audiology‐led ENTICES decisions were amended by hospital otologists following remote review. Remote review of video‐otoscopy with history was sufficient for a diagnosis in 80% of cases. Adding hearing tests and standardised history increased the diagnostic yield to 98%. Patient satisfaction scores showed 100% service recommendation. The cost per patient, per visit, was £83.36, £99.07 and £69.72 for AAD, HOC or ENTICES, respectively.

Conclusion

ENTICES provides a safe ear and hearing service that patients rated highly. Thirty‐two per cent of hospital otology patients were eligible for this service. For those patients, ENTICES is 20% more cost‐effective and can reduce the number of clinic visits by up to 60% compared with HOC.
Retrospective study on pomalidomide‐PACE as a salvage regimen in aggressive relapsed and refractory multiple myeloma
Authors: Gezer Deniz , Nogueira Melanie Schmitt , Kirschner Martin , Brümmendorf Tim H. , Müller‐Tidow Carsten , Goldschmidt Hartmut , Raab Marc S. , Giesen Nicola
Published: June 2024

Objectives

Despite major advances in treatment options for multiple myeloma (MM), patients refractory to the main drug classes and those with aggressive, especially extramedullary disease, still face a dismal outcome. For these patients, effective therapeutic options are urgently warranted.

Methods

In this retrospective study, we report on the safety and efficacy of the intensive combination regimen of pomalidomide plus cisplatin, doxorubicin, cyclophosphamide, and etoposide (Pom‐PACE) in patients with relapsed refractory MM (RRMM) or plasma cell leukemia (PCL). A study population of 20 consecutive patients treated with Pom‐PACE at two academic centers was included for analysis. All patients had to have a confirmed relapse according to International Myeloma Working Group criteria and adequate organ function prior to the start of therapy. Data were collected by reviewing medical charts. Exploratory analyses were performed with regard to efficacy and safety.

Results

Patients were heavily pretreated with a median number of four prior therapies (range: 1–10). All patients were exposed to immunomodulators, proteasome inhibitors, and alkylating agents, 80% were double‐class refractory, 40% were triple‐class refractory. Extramedullary MM or PCL were present in 15 patients (75%). Overall response rate (ORR) was 68%, with 31% achieving at least a very good partial response. Responses were achieved rapidly with an ORR of 64% after one cycle. Median progression‐free survival was 8.9 months (0.92–not reached [NR]) and median overall survival was 11.8 months (3–40.6). Pom‐PACE was associated with significant toxicity. All evaluable patients experienced Grade 4 hematological toxicity. However, no treatment related mortality was observed.

Conclusion

Pomalidomide‐PACE was able to induce rapid responses in heavily pretreated, aggressive RRMM with a manageable toxicity profile and therefore offers an effective salvage regimen and a potential bridging strategy to further treatment options such as chimeric antigen receptor T‐cell therapy.
The challenge of estimating global termite methane emissions
Authors: Law Stephanie J. , Allison Steven D. , Davies Andrew B. , Flores‐Moreno Habacuc , Wijas Baptiste J. , Yatsko Abbey R. , Zhou Yong , Zanne Amy E. , Eggleton Paul
Published: June 2024

Methane is a powerful greenhouse gas, more potent than carbon dioxide, and emitted from a variety of natural sources including wetlands, permafrost, mammalian guts and termites. As increases in global temperatures continue to break records, quantifying the magnitudes of key methane sources has never been more pertinent. Over the last 40 years, the contribution of termites to the global methane budget has been subject to much debate. The most recent estimates of termite emissions range between 9 and 15 Tg CH4 year−1, approximately 4% of emissions from natural sources (excluding wetlands). However, we argue that the current approach for estimating termite contributions to the global methane budget is flawed. Key parameters, namely termite methane emissions from soil, deadwood, living tree stems, epigeal mounds and arboreal nests, are largely ignored in global estimates. This omission occurs because data are lacking and research objectives, crucially, neglect variation in termite ecology. Furthermore, inconsistencies in data collection methods prohibit the pooling of data required to compute global estimates. Here, we summarise the advances made over the last 40 years and illustrate how different aspects of termite ecology can influence the termite contribution to global methane emissions. Additionally, we highlight technological advances that may help researchers investigate termite methane emissions on a larger scale. Finally, we consider dynamic feedback mechanisms of climate warming and land‐use change on termite methane emissions. We conclude that ultimately the global contribution of termites to atmospheric methane remains unknown and thus present an alternative framework for estimating their emissions. To significantly improve estimates, we outline outstanding questions to guide future research efforts.
Global Primary Antibiotic Resistance Rate of Helicobacter pylori in Recent 10 years: A Systematic Review and Meta‐Analysis
Authors: Yu Yanhui , Xue Jing , Lin Fangbing , Liu Daming , Zhang Wen , Ru Shuying , Jiang Feng
Published: June 2024

Introduction

Due to irregular antibiotic use, the rate of antibiotic resistance to Helicobacter pylori (H. pylori) is increasing and varies from region to region. Therefore, for the purpose of further clarifying the changes in antibiotic resistance rates nowadays, we conducted a systematic review and meta‐analysis to update and assess the 10‐year trend of primary H. pylori antibiotic resistance rate to the commonly prescribed antibiotics worldwide.

Materials and Methods

According to the PRISMA statement, we systematically searched electronic databases for studies that assessed rates of H. pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline published from 2013 to 2023. AHRQ was adopted to estimate methodological quality and publication bias in the included studies, and statistical analysis was performed using Stata 17.0.

Results

We identified 163 studies, comprising 47,002 isolates from 36 countries. The meta‐analysis showed that the primary antibiotic resistance rate of H. pylori varied widely among antibiotics. Subgroup analysis showed higher rates of antibiotic resistance in the adult population than in children, and a general trend of increased resistance was observed from 2013 to 2023. There was considerable heterogeneity (I2 > 75%) among all analyses, which may be due to high variability in resistance rates across the global regions.

Conclusions

Resistance of H. pylori to antibiotics has reached alarming levels worldwide, which has a great effect on the efficacy of treatment. Local surveillance networks are required to select appropriate eradication regimens for each region.
Exploring the Experiences of Living With the Post‐COVID Syndrome: A Qualitative Study
Authors: Kalfas Michail , Jolley Caroline , Hart Nicholas , Rafferty Gerrard F. , Duncan Emma L. , Nicholson Timothy , Ashworth Mark , Brewin Debbie , Barrett Barbara , Witard Oliver C. , Ridge Damien , Chalder Trudie
Published: June 2024

Introduction

Many people experience persistent symptoms for more than 12 weeks following SARS‐CoV‐2 infection, which is known as post‐COVID‐19 condition (PCS) or Long COVID (LC). PCS can impair people's quality of life and daily functioning. However, there is a lack of in‐depth research exploring the PCS patient journey, as well as gendered aspects of patients' experiences.

Methods

Nineteen semi‐structured qualitative interviews were conducted with people living with PCS in the United Kingdom (13 women, 6 men). Interviews were transcribed verbatim and analysed inductively using reflexive thematic analysis.

Results

Five main themes were identified: ‘Symptom dismissal’, ‘Lack of information and support’, ‘Life before and after Long COVID’, ‘Psychological impact’ and ‘Acceptance’. A shift overtime to self‐management of symptoms was evident. These themes represent different stages of patients' PCS journey. Narratives indicated that women highlighted dismissal by healthcare professionals (HCPs), which was not as prominent in men's narratives. In addition, women went into more detail about the psychological impact of PCS compared to men.

Conclusion

Women with PCS reported symptom dismissal by HCPs, which may have delayed their diagnosis and negatively affected their well‐being. We were not able to explore the experiences of people from non‐conforming gender groups. Raising awareness of these issues among HCPs, particularly general practitioners, could improve patient care in PCS.

Patient or Public Contribution

Patient and public involvement consisted of people who took part in the interviews and commented on the themes' interpretation and study conclusions.
Application of Johnson's approximation in finite element modeling for electric field‐dependent materials
Authors: D'Silva Green Rassell C. , Dale Graham , McLaughlin Garry , Strawhorne Maureen , Sinclair Derek C. , Dean Julian S.
Published: June 2024

Johnson's approximation is implemented in a finite element code to simulate the electric field dependence of a core–shell microstructure material. We show how the microstructure, based here on a 50:50 volume fraction, influences the measured effective permittivity as a function of applied voltage. Using a Johnson's parameter of β = 1.0 × 1010 Vm5/C3, verified from commercial BaTiO3‐based multilayer ceramic capacitors (MLCC), we show how the microstructure and the difference in core and shell conductivities alter the local fields generated and how this influences the voltage dependence of the effective permittivity. Systems that comprise a conductive core‐like material surrounded by a resistive shell experience little or modest voltage dependence due to the shell material providing shielding to large electric fields within the cores. Conversely, if the core material is more resistive than the shell material, substantial voltage dependence occurs with simulations showing over a 50% decrease in the effective permittivity. These simulations give improved understanding of voltage dependence and provide a method to help guide the design of future materials for MLCCs with improved performance.
Anthropogenic nesting substrates increase parental fitness in a Neotropical songbird, the pale‐breasted thrush Turdus leucomelas
Authors: Batisteli Augusto Florisvaldo , Sarmento Hugo , Aurélio Pizo Marco
Published: June 2024

The failure of breeding attempts is a major hindrance to bird reproduction, making nest site choice under strong selective pressure. Urbanization may offer lower risk of nest predation to certain bird species, but the impact of using anthropogenic structures as nesting sites on parental fitness is seldom studied. We studied the effect of anthropogenic substrates and brood parasitism by the shiny cowbird Molothrus bonariensis on the nest success of a Neotropical songbird, the pale‐breasted thrush Turdus leucomelas. We monitored 263 nesting attempts between 2017 and 2020 to estimate daily survival rate (DSR), which represents the probability of a given nest surviving until the next day. DSR was modelled as a response variable in function of substrate type (plants as ‘natural' or human buildings as ‘artificial') and brood parasitism as fixed factors, using as covariates year, a linear and a quadratic seasonal trends. Additionally, we tested the effect of these same explanatory variables on the number of fledglings per nest using a generalized linear mixed‐effects model. Most nests (78.7%) were placed in artificial substrates and apparent nest success (i.e. the percentage of nesting attempts that produced at least one thrush fledgling) was higher in artificial (50.2%) than in natural substrates (37.5%). DSR was higher for nests in artificial than in natural substrates regardless of cowbird parasitism, whereas the number of fledglings per nest was higher both in artificial substrates and for nests without cowbird parasitism. We highlight that nesting in buildings significantly increases parental fitness in pale‐breasted thrushes, which may favor their settlement in cities and potentially drive the evolution of this breeding behavior in urban birds.
Combined analysis of the effects of hypoxia and oxidative stress on DNA methylation and the transcriptome in HTR‐8/SVneo trophoblast cells
Authors: Yan Xinjing , Fang Yang , Yuan Yujie , Ding Yangnan , Yu Haiyang , Li Yina , Shi Qianqian , Gao Yongrui , Zhou Xinyuan , Zhang Dongxin , Yuan Enwu , Zhou Hongwei , Zhao Xin , Zhang Linlin
Published: June 2024

The alterations in DNA methylation and transcriptome in trophoblast cells under conditions of low oxygen and oxidative stress have major implications for pregnancy‐related disorders. However, the exact mechanism is still not fully understood. In this study, we established models of hypoxia (H group) and oxidative stress (HR group) using HTR‐8/SVneo trophoblast cells and performed combined analysis of genome‐wide DNA methylation changes using reduced representation bisulphite sequencing and transcriptome expression changes using RNA sequencing. Our findings revealed that the H group exhibited a higher number of differentially methylated genes and differentially expressed genes than the HR group. In the H group, only 0.90% of all differentially expressed genes displayed simultaneous changes in DNA methylation and transcriptome expression. After the threshold was expanded, this number increased to 6.29% in the HR group. Notably, both the H group and HR group exhibited concurrent alterations in DNA methylation and transcriptome expression within Axon guidance and MAPK signalling pathway. Among the top 25 differentially methylated KEGG pathways in the promoter region, 11 pathways were commonly enriched in H group and HR group, accounting for 44.00%. Among the top 25 KEGG pathways in transcriptome with significant differences between the H group and HR group, 10 pathways were consistent, accounting for 40.00%. By integrating our previous data on DNA methylation from preeclamptic placental tissues, we identified that the ANKRD37 and PFKFB3 genes may contribute to the pathogenesis of preeclampsia through DNA methylation‐mediated transcriptome expression under hypoxic conditions.
An analysis of AURKB's prognostic and immunological roles across various cancers
Authors: Li Jun , Cheng Cui , Zhang Jiajun
Published: June 2024

Aurora kinase B (AURKB), an essential regulator in the process of mitosis, has been revealed through various studies to have a significant role in cancer development and progression. However, the specific mechanisms remain poorly understood. This study, therefore, seeks to elucidate the multifaceted role of AURKB in diverse cancer types. This study utilized bioinformatics techniques to examine the transcript, protein, promoter methylation and mutation levels of AURKB. The study further analysed associations between AURKB and factors such as prognosis, pathological stage, biological function, immune infiltration, tumour mutational burden (TMB) and microsatellite instability (MSI). In addition, immunohistochemical staining data of 50 cases of renal clear cell carcinoma and its adjacent normal tissues were collected to verify the difference in protein expression of AURKB in the two tissues. The results show that AURKB is highly expressed in most cancers, and the protein level of AURKB and the methylation level of its promoter vary among cancer types. Survival analysis showed that AURKB was associated with overall survival in 12 cancer types and progression‐free survival in 11 cancer types. Elevated levels of AURKB were detected in the advanced stages of 10 different cancers. AURKB has a potential impact on cancer progression through its effects on cell cycle regulation as well as inflammatory and immune‐related pathways. We observed a strong association between AURKB and immune cell infiltration, immunomodulatory factors, TMB and MSI. Importantly, we confirmed that the AURKB protein is highly expressed in kidney renal clear cell carcinoma (KIRC). Our study reveals that AURKB may be a potential biomarker for pan‐cancer and KIRC.
Titanium dioxide in face powders and eyeshadows: Developing an analytical methodology for accessing customer safety
Authors: Amorello Diana , Ferrara Marzia , Orecchio Santino
Published: June 2024

Background

Titanium dioxide (TiO2), a white powder, represents the opacifier used in many products, including drugs, foods, cosmetics, paints, and dyes.

Method

The Uv‐Vis spectrophotometry was a particularly suitable technique to quantify TiO2 in the solutions obtained from cosmetics. In this work, we determined the TiO2 content in a total of 88 samples of eye shadows and face powders of different brands and costs. Before to analyse the samples, we developed the mineralization and analysis method, in fact, fusion with potassium bisulphate would be very laborious because it must be carried out on one sample at a time and requires very long times, instead, the mineralization with the acid mixture and the aid of microwaves allowed us to solubilize six samples at the same time within 45 min.

Results

From the results obtained, we can state that the highest concentrations of TiO2 are found in the eyeshadows with a maximum value of 36% in a blue eyeshadow.
Perspective on oral processing of plant‐based beverages
Authors: George Gintu Sara , Fleming Craig J. , Upadhyay Rituja
Published: June 2024

Around the world, the market for plant‐derived beverages is one of the fastest‐expanding segments in the functional and specialty beverage areas of newer food product development. Consumers are increasingly likely to choose alternatives to bovine beverages due to factors including lactose intolerance, hypercholesterolemia prevalence, allergies to bovine beverages, and preference for vegan diets that contain functionally active ingredients with health‐promoting characteristics. Due to health, ecological, and ethical concerns, many customers are interested in reducing their usage of animal products like bovine milk. A variety of plant‐based beverage substitutes are being created by the food sector as a result. To create viable alternatives, it is first necessary to provide an overview of the chemical composition, structure, features, and nutritional attributes of ordinary bovine milk. Sensory acceptability in the case of substitutes for beverages made from legumes is a significant barrier to their widespread acceptance, and thus saliva acts as a sophisticated fluid that serves a variety of purposes in the cavity of the mouth. Designing and producing next‐generation plant‐based beverages that mimic the physicochemical and functional qualities of conventional bovine‐based beverages is gaining popularity, and many of these products can be thought of as colloidal materials that contain the particles or polymers that give them their unique qualities NG‐PB foods can have a wide range of rheological qualities, such as fluids with low viscosity (such as plant‐based beverages), high‐viscosity liquids (like creams), soft liquids (like yogurt), as well as hard solids (such as some cheeses).
Limited effects of xylem anatomy on embolism resistance in cycad leaves
Authors: Jiang Guo‐Feng , Qin Bo‐Tao , Pang Yu‐Kun , Qin Lan‐Li , Pereira Luciano , Roddy Adam B.
Published: June 2024

Drought‐induced xylem embolism is a primary cause of plant mortality. Although c. 70% of cycads are threatened by extinction and extant cycads diversified during a period of increasing aridification, the vulnerability of cycads to embolism spread has been overlooked.

We quantified the vulnerability to drought‐induced embolism, pressure–volume curves, in situ water potentials, and a suite of xylem anatomical traits of leaf pinnae and rachises for 20 cycad species. We tested whether anatomical traits were linked to hydraulic safety in cycads.

Compared with other major vascular plant clades, cycads exhibited similar embolism resistance to angiosperms and pteridophytes but were more vulnerable to embolism than noncycad gymnosperms. All 20 cycads had both tracheids and vessels, the proportions of which were unrelated to embolism resistance. Only vessel pit membrane fraction was positively correlated to embolism resistance, contrary to angiosperms. Water potential at turgor loss was significantly correlated to embolism resistance among cycads.

Our results show that cycads exhibit low resistance to xylem embolism and that xylem anatomical traits – particularly vessels – may influence embolism resistance together with tracheids. This study highlights the importance of understanding the mechanisms of drought resistance in evolutionarily unique and threatened lineages like the cycads.
Introduction
Authors: Hearne Siobhán , Campbell Ian W.
Published: June 2024

This cluster of articles explores the gendered history of the military in the Russian imperial and Soviet contexts during periods of imperial conquest, war, and their complex aftermaths. The cluster began at the 2021 ASEEES virtual convention, when the contributors joined the Zoom panel while their respective countries were in various stages of lockdown. Chronologically, the cluster stretches from the middle of the nineteenth century to the 1960s, with two articles on the Russian Empire and two covering the Soviet period. From the imperial borderlands of the Caucasus in the nineteenth century to the Nazi‐occupied western frontiers of the Soviet Union during the Second World War, ideas about appropriate feminine and masculine behavior shaped the enactment of and reactions to violence. Veterans of the Russo‐Japanese and Second World Wars drew on vocabularies of military masculinity to claim authority within their respective postwar societies. In this short introduction, we reflect on the relationship between gender history and military history and underline the importance of integrating the Russian/Soviet case into international historiographies of gender and war.
Minimum Intensity of Daily Six Eccentric Contractions to Increase Muscle Strength and Size
Authors: Yoshida Riku , Murakami Yuta , Kasahara Kazuki , Sato Shigeru , Nosaka Kazunori , Nakamura Masatoshi
Published: June 2024

Our previous study showed that daily six maximal eccentric contractions that were performed 5 days a week for 4 weeks increased maximal voluntary isometric (MVC‐ISO), concentric (MVC‐CON), and eccentric contraction (MVC‐ECC) strength of the elbow flexors and muscle thickness of biceps brachii and brachialis (MT) by 8.3 ± 4.9%, 11.1 ± 7.4%, 13.5 ± 11.5%, and 10.6 ± 5.1%, respectively. In the present study, we tested the hypothesis that the muscle strength and MT would still increase when the training intensity was reduced to 2/3 or 1/3 of the peak MVC‐ECC torque. Thirty‐six healthy young (19–24 years) adults who had not performed resistance training were placed to three groups (n = 12/group): 2/3MVC or 1/3MVC that performed six eccentric contractions with 2/3 or 1/3 MVC‐ECC load using a dumbbell 5 days a week for 4 weeks or control group that did not perform any training. Changes in the MVC‐ISO, MVC‐CON, MVC‐ECC torque, and MT before and after the 4‐week period were compared among the groups and with the group of the previous study in which six maximal eccentric contractions were performed 5 days a week for 4 weeks (MVC group; n = 12). The control and 1/3MVC groups showed no significant changes in any measures. Significant (p < 0.05) increases in MVC‐ISO (10.3 ± 11.4%), MVC‐CON (10.9 ± 9.5%), and MVC‐ECC (9.3 ± 8.8%) torque and MT (10.1 ± 9.2%) were observed for the 2/3MVC group. These changes were not significantly different from those of the MVC group. These results suggest that the 2/3‐intensity eccentric contractions with a dumbbell are as effective as maximal‐intensity isokinetic eccentric contractions to induce muscle adaptations.
Obstacles of Instructors in Writing and Publishing International Journal Articles: A Study of Theological Schools in Indonesia
Authors: Leo Sutanto , Suryaningsih Eko Wahyu , Nugraeni Giarti
Published: June 2024

The aim of this study is to investigate obstacles faced by Indonesian theological schools' lecturers in writing and publishing international journal articles. Using a thematic analysis technique, qualitative information from in‐depth interviews with 18 lecturers was examined, and 216 lecturers' quantitative responses were examined using the Likert scale. The findings show that the lecturers have barriers particularly in terms of fluency, structure, diction, and writing techniques in writing English language journal articles. They encounter issues with research financing, publication costs, and journal article publication standards. It is proposed that in order to overcome these barriers, the lecturers should be guided and given training on how to use English, particularly while writing articles. In addition, their institutions should reconsider their policies on transfer of funding due to the barriers' existing policies pose to research funding and publication.
Winged horses, rascals and discourse referents
Authors: Stokke Andreas
Published: June 2024

This paper discusses some remarks Kaplan made in ‘Bob and Carol and Ted and Alice’ concerning empty names. I show how his objections to a particular view involving descriptions derived from Ramsification can be avoided by a nearby alternative framed in terms of discourse reference. I offer a treatment of empty names as variables carrying presuppositions concerning unique occupants of roles, or sets of properties, determined by the originating discourse.
2024 Guidelines for reporting radiation therapy in veterinary medicine
Authors: Willows Brooke , Melhus Christopher
Published: June 2024

Evidence‐based medicine drives patient care decision‐making; thus, accurate and complete reporting in scientific publications is paramount. A checklist for complete reporting of veterinary radiation therapy was proposed in 2012 using the recommendations of the International Commission of Radiation Units and Measurements (ICRU). The purpose of this study is to review the 2012 checklist and propose updates based on changes in technology. Significant technology advancements have gained traction in veterinary medicine, including intensity‐modulated radiation therapy (IMRT) and stereotactic radiation therapy (SRT), both of which have related modality‐specific ICRU reporting recommendations. The 2012 checklist and proposed 2024 checklist are then used to assess the completeness of reporting in veterinary radiation oncology publications between 2015 and 2022, of which one hundred and eight publications met the inclusion criteria. Prior to the publication of the 2012 checklist (2005–2010), only nine checklist items showed a good level of completeness in reporting, and from 2015 to 2022, this increased to 16 items. Encouraging and/or requiring the use of reporting checklists at the time of manuscript submission may be responsible for this improvement in reporting. Using the 2024 checklist, which is more relevant to publications discussing IMRT and SRT treatments, only 14 of the analyzed checklist items (34%) show a good level of completeness in reporting, suggesting there is a need for updated guidelines to capture the nuances of advanced techniques. This study proposes a 2024 checklist that can be used as a guideline for future reporting of radiation therapy in veterinary medicine.
Collagen architecture and biomechanics of gracilis and adductor longus muscles from children with cerebral palsy
Authors: Wohlgemuth Ross P. , Kulkarni Vedant A. , Villalba Marie , Davids Jon R. , Smith Lucas R.
Published: June 2024

Cerebral palsy (CP) describes some upper motoneuron disorders due to non‐progressive disturbances occurring in the developing brain that cause progressive changes to muscle. While longer sarcomeres increase muscle stiffness in patients with CP compared to typically developing (TD) patients, changes in extracellular matrix (ECM) architecture can increase stiffness. Our goal was to investigate how changes in muscle and ECM architecture impact muscle stiffness, gait and joint function in CP. Gracilis and adductor longus biopsies were collected from children with CP undergoing tendon lengthening surgery for hamstring and hip adduction contractures, respectively. Gracilis biopsies were collected from TD patients undergoing anterior cruciate ligament reconstruction surgery with hamstring autograft. Muscle mechanical testing, two‐photon imaging and hydroxyproline assay were performed on biopsies. Corresponding data were compared to radiographic hip displacement in CP adductors (CPA), gait kinematics in CP hamstrings (CPH), and joint range of motion in CPA and CPH. We found at matched sarcomere lengths muscle stiffness and collagen architecture were similar between TD and CP hamstrings. However, CPH stiffness (R2 = 0.1973), collagen content (R2 = 0.5099) and cross‐linking (R2 = 0.3233) were correlated to decreased knee range of motion. Additionally, we observed collagen fibres within the muscle ECM increase alignment during muscular stretching. These data demonstrate that while ECM architecture is similar between TD and CP hamstrings, collagen fibres biomechanics are sensitive to muscle strain and may be altered at longer in vivo sarcomere lengths in CP muscle. Future studies could evaluate the impact of ECM architecture on TD and CP muscle stiffness across in vivo operating ranges.

image

Key points

At matched sarcomere lengths, gracilis muscle mechanics and collagen architecture are similar in TD patients and patients with CP.

In both TD and CP muscles, collagen fibres dynamically increase their alignment during muscle stretching.

Aspects of muscle mechanics and collagen architecture are predictive of in vivo knee joint motion and radiographic hip displacement in patients with CP.

Longer sarcomere lengths in CP muscle in vivo may alter collagen architecture and biomechanics to drive deficits in joint mobility and gait function.
Maxwell and the development of electromagnetic theory
Authors: Bork Alfred M.
Published: June 2024

This article presents an unpublished manuscript by Alfred M. Bork that was written in 1976 as an introduction to a collection of Maxwell's papers on electromagnetism which was never published. It provides encouragement to the reader to study the original works of Maxwell on electromagnetism, and this encouragement is as timely today as in 1976.
Team Identity and Environmentalism: The Case of Forest Green Rovers
Authors: Delia Elizabeth B. , McCullough Brian P. , Dalal Keegan
Published: June 2024

Despite consumer concern over climate change, research on environmental issues and sport fandom has focused more on organizational outcomes than on fans themselves. Recognizing fandom can be representative of social movements, and social identity and collective action are utilized in an intrinsic case study of Forest Green Rovers football club supporters (who also identify with environmentalism) to understand the extent to which the club represents a social movement, and whether Forest Green Rovers’ sustainability efforts encourage pro-environment actions. Through interview research, we found supporters’ team and environmental identities cooperate synergistically. Forest Green Rovers is not just representative of environmentalism but has become a politicized identity itself—a means to act for change on environmental issues. We discuss implications concerning identity synergy, team identity as a politicized identity, perceptions of success, collective action, and cognitive alternatives to the status quo. We conclude by noting the unavoidable inseparability of environmental issues and sport consumption.
Approaching the quantum limit of contact resistance in van der Waals layered semiconductors
Authors: Lee Young Hee
Published: June 2024

The field-effect transistor (FET) is a cornerstone of modern electronics, pivotal in the development of compact and efficient integrated microprocessors and memory storage devices capable of low-power operation. At the heart of a FET is a semiconductor channel, typically made of materials such as silicon, which links the source to the drain. Positioned directly beneath an insulator that overlays the gate, this channel's conductivity or mobility, which measures the ease of current flow, is controlled by the electric field resulting from the voltage applied to the gate. Consequently, this setup allows the gate voltage to modulate the current, effectively turning it on and off.
Republicans float plan to overhaul NIH
Authors: Kaiser Jocelyn
Published: June 2024

Lawmakers propose reducing 27 institutes to 15
Pharmacokinetics and pharmacodynamics of intravenous delafloxacin in healthy subjects: model-based dose optimization
Authors: Lv Jiong-Xian , Huang Yi-Huan , Kafauit Farah , Wang Yuan-Hui , Su Chang , Ma Jun-Heng , Xu Yan , Huang Chao-Chao , Zhang Qing , Su Yu-Wen
Published: June 2024

Delafloxacin, a fluoroquinolone antibiotic to treat skin infections, exhibits a broad-spectrum antimicrobial activity. The first randomized, open-label phase I clinical trial was conducted to assess the safety and pharmacokinetics (PK) of intravenous delafloxacin in the Chinese population. A population pharmacokinetic (PopPK) model based on the clinical trial was conducted by NONMEM software. Monte Carlo simulation was performed to evaluate the antibacterial effects of delafloxacin at different doses in different Chinese populations. The PK characteristics of delafloxacin were best described by a three-compartment model with mixed linear and nonlinear clearance. Body weight was included as a covariate in the model. We simulated the AUC
0-24h
in a steady state at five doses in patient groups of various weights. The results indicated that for patients weighing 70 kg and treated with methicillin-resistant
Staphylococcus aureus
(MRSA) infections, a minimum dose of 300 mg achieved a PTA > 90% at MIC
90
of 0.25 µg/mL, suggesting an ideal bactericidal effect. For patients weighing less than 60 kg, a dose of 200 mg achieved a PTA > 90% at MIC
90
of 0.25 µg/mL, also suggesting an ideal bactericidal effect. Additionally, this trial demonstrated the high safety of delafloxacin in single-dose and multiple-dose groups of Chinese. Delafloxacin (300 mg, q12h, iv) was recommended for achieving optimal efficacy in Chinese bacterial skin infections patients. To ensure optimal efficacy, an individualized dose of 200 mg (q12h, iv) could be advised for patients weighing less than 60 kg, and 300 mg (q12h, iv) for those weighing more than 60 kg.
Development and evaluation of an intensive short course: the Quantitative Microbial Risk Assessment Interdisciplinary Instructional Institute (QMRA III)
Authors: Mitchell Jade , Li Hongwan , Weir Mark H. , Libarkin Julie , Pasek Emily
Published: June 2024

Quantitative microbial risk assessment (QMRA) is a growing interdisciplinary field addressing exposures to microbial pathogens and infectious disease processes. Risk science is inherently interdisciplinary, but few of the contributing disciplinary programs offer courses and training specifically in QMRA. To develop multidisciplinary training in QMRA, an annual 10-day long intensive workshop was conducted from 2015 to 2019—the Quantitative Microbial Risk Assessment Interdisciplinary Instructional Institute (QMRA III). National leaders in the fields of public health, engineering, microbiology, epidemiology, communications, public policy, and QMRA served as instructors and mentors over the course of the program. To provide cross-training, multidisciplinary teams of 5–6 trainees were created from the approximately 30 trainees each year. A formal assessment of the program was performed based on observations and surveys containing Likert-type scales and open-ended prompts. In addition, a longitudinal alumni survey was also disseminated to facilitate the future redevelopment of QMRA institutes and determine the impact of the program. Across all years, trainees experienced statistically significant increases (
P
< 0.05) in their perceptions of their QMRA abilities (e.g., use of specific computer programs) and knowledge of QMRA constructs (e.g., risk management). In addition, 12 publications, three conference presentations, and two research grants were derived from the QMRA III institute projects or tangential research. The success of QMRA III indicates that a short course format can effectively address many multidisciplinary training needs. Key features of QMRA III, including the inter-disciplinary training approach, hands-on exercises, real-world institute projects, and interaction through a mentoring process, were vital for training multidisciplinary teams housing multiple forms of expertise. Future QMRA institutes are being redeveloped to leverage hybrid learning formats that can further the multidisciplinary training and mentoring objectives.
Genetic barrier to resistance: a critical parameter for efficacy of neutralizing monoclonal antibodies against SARS-CoV-2 in a nonhuman primate model
Authors: Stahl-Hennig Christiane , Peter Antonia Sophia , Cordsmeier Arne , Stolte-Leeb Nicole , Vestweber Ramona , Socher Eileen , Merida Samuel Alberto , Sauermann Ulrike , Bleyer Martina , Fraedrich Kirsten , Grunwald Thomas , Winkler Thomas H. , Ensser Armin , Jäck Hans-Martin , Überla Klaus
Published: June 2024

The potency of antibody neutralization in cell culture has been used as the key criterion for selection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for clinical development. As other aspects may also influence the degree of protection
in vivo
, we compared the efficacy of two neutralizing monoclonal antibodies (TRES6 and 4C12) targeting different epitopes of the receptor binding domain (RBD) of SARS-CoV-2 in a prophylactic setting in rhesus monkeys. All four animals treated with TRES6 had reduced viral loads in the upper respiratory tract 2 days after naso-oropharyngeal challenge with the Alpha SARS-CoV-2 variant. Starting 2 days after challenge, mutations conferring resistance to TRES6 were dominant in two of the rhesus monkeys, with both animals failing to maintain reduced viral loads. Consistent with its lower serum neutralization titer at the day of challenge, prophylaxis with 4C12 tended to suppress viral load at day 2 less efficiently than TRES6. However, a week after challenge, mean viral loads in the lower respiratory tract in 4C12-treated animals were lower than in the TRES6 group and no mutations conferring resistance to 4C12 could be detected in viral isolates from nasal or throat swabs. Thus, genetic barrier to resistance seems to be a critical parameter for the efficacy of prophylaxis with monoclonal antibodies against SARS-CoV-2. Furthermore, comparison of antibody concentrations in respiratory secretions to those in serum shows reduced distribution of the 4C12 antibody into respiratory secretions and a delay in the appearance of antibodies in bronchoalveolar lavage fluid compared to their appearance in secretions of the upper respiratory tract.

IMPORTANCE

Monoclonal antibodies are a powerful tool for the prophylaxis and treatment of acute viral infections. Hence, they were one of the first therapeutic agents licensed for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Oftentimes, the main criterion for the selection of antibodies for clinical development is their potency of neutralization in cell culture. By comparing two antibodies targeting the Spike protein of SARS-CoV-2, we now observed that the antibody that neutralized SARS-CoV-2 more efficiently in cell culture suppressed viral load in challenged rhesus monkeys to a lesser extent. Extraordinary rapid emergence of mutants of the challenge virus, which had lost their sensitivity to the antibody, was identified as the major reason for the reduced efficacy of the antibody in rhesus monkeys. Therefore, the viral genetic barrier to resistance to antibodies also affects their efficacy.
Broadly protective bispecific antibodies that simultaneously target influenza virus hemagglutinin and neuraminidase
Authors: Ramos Kevin E. , Okba Nisreen M. A. , Tan Jessica , Bandawane Pooja , Meade Philip S. , Loganathan Madhumathi , Francis Benjamin , Shulenin Sergey , Holtsberg Frederick W. , Aman M. Javad , McMahon Meagan , Krammer Florian , Lai Jonathan R.
Published: June 2024

Monoclonal antibodies (mAbs) are an attractive therapeutic platform for the prevention and treatment of influenza virus infection. There are two major glycoproteins on the influenza virion surface: hemagglutinin (HA), which is responsible for viral attachment and entry, and neuraminidase (NA), which mediates viral egress by enzymatically cleaving sialic acid to release budding particles from the host cell surface. Broadly neutralizing antibodies (bNAbs) that target the conserved HA central stalk region, such as CR9114, can inhibit both viral entry and egress. More recently, broadly binding mAbs that engage and inhibit the NA active site, such as 1G01, have been described to prevent viral egress. Here, we engineered bispecific antibodies (bsAbs) that combine the variable domains of CR9114 and 1G01 into a single molecule and evaluated if simultaneous targeting of two different glycoproteins improved antiviral properties
in vitro
and
in vivo
. Several CR9114/1G01 bsAbs were generated with various configurations of the two sets of the variable domains (“bsAb formats”). We found that combinations employing the addition of a single-chain variable fragment in the hinge region of an IgG scaffold had the best properties in terms of expression, stability, and binding. Further characterization of selected bsAbs showed potent neutralizing and egress-inhibiting activity. One such bsAb (“hSC_CR9114_1G01”) provided higher levels of prophylactic protection from mortality and morbidity upon challenge with H1N1 than either of the parental mAbs at low dosing (1 mg/kg). These results highlight the potential use of bsAbs that simultaneously target HA and NA as new influenza immunotherapeutics.

IMPORTANCE

Infection by the influenza virus remains a global health burden. The approaches utilized here to augment the activity of broadly protective influenza virus antibodies may lead to a new class of immunotherapies with enhanced activity.
IL-9 plays a critical role in helminth-induced protection against COVID-19-related cytokine storms
Authors: Xiang ChunXiao , Zhong Gang , Wang Huiqing
Published: June 2024

A recent study published in
mBio
by Cao et al. demonstrated that the helminth
Trichinella sprialis
(Ts) alleviates COVID-19-related cytokine storms in an IL-9-dependent way (Z. Cao, J. Wang, X. Liu, Y. Liu, et al., mBio 15:e00905-24, 2024,
https://doi.org/10.1128/mbio.00905-24
). A cytokine storm is a severe immune response characterized by the overproduction of proinflammatory cytokines, such as TNF-α and IFN-γ, leading to tissue damage and mortality in COVID-19 patients. This study indicated that IL-9 is crucial in protecting against cytokine storm syndromes associated with SARS-CoV-2 infection and proposed that anti-inflammatory molecules from Ts excretory/secretory (TsES) products could be a novel source for treating such illnesses.
Whole-genome sequence of
Mucor velutinosus
NIH1002, a strain associated with disseminated disease
Authors: Conlan Sean , Subramanian Poorani , Plata Barril Beatriz , Youn Jung-Ho , Thomas Pamela J. , Koren Sergey , Dotson Gabrielle A. , Park Morgan , Rhie Arang , Segre Julie A. , Dekker John P. , Zelazny Adrian M.
Published: June 2024

The draft genome of
Mucor velutinosus
NIH1002, a 2011 isolate from a case of disseminated disease, was sequenced using PacBio long-read and HiSeq short-read technologies. The genome has 43 contigs, an N50 of 2.65 Mb, and 13,295 protein-coding genes. It is the most complete
M. velutinosus
genome to date.
Association between semen microbiome disorder and sperm DNA damage
Authors: He Junxian , Ma Menghui , Xu Zhenhan , Guo Jintao , Chen Haicheng , Yang Xing , Chen Peigen , Liu Guihua
Published: June 2024

DNA fragmentation index (DFI), a new biomarker to diagnose male infertility, is closely associated with poor reproductive outcomes. Previous research reported that seminal microbiome correlated with sperm DNA integrity, suggesting that the microbiome may be one of the causes of DNA damage in sperm. However, it has not been elucidated how the microbiota exerts their effects. Here, we used a combination of 16S rRNA sequencing and untargeted metabolomics techniques to investigate the role of microbiota in high sperm DNA fragmentation index (HDFI). We report that increased specific microbial profiles contribute to high sperm DNA fragmentation, thus implicating the seminal microbiome as a new therapeutic target for HDFI patients. Additionally, we found that the amount of
Lactobacillus
species was altered:
Lactobacillus iners
was enriched in HDFI patients, shedding light on the potential influence of
L. iners
on male reproductive health. Finally, we also identified enrichment of the acetyl-CoA fermentation to butanoate II and purine nucleobase degradation I in the high sperm DNA fragmentation samples, suggesting that butanoate may be the target metabolite of sperm DNA damage. These findings provide valuable insights into the complex interplay between microbiota and sperm quality in HDFI patients, laying the foundation for further research and potential clinical interventions.

IMPORTANCE

The DNA fragmentation index (DFI) is a measure of sperm DNA fragmentation. Because high sperm DNA fragmentation index (HDFI) has been strongly associated with adverse reproductive outcomes, this has been linked to the seminal microbiome. Because the number of current treatments for HDFI is limited and most of them have no clear efficacy, it is critical to understand how semen microbiome exerts their effects on sperm DNA. Here, we evaluated the semen microbiome and its metabolites in patients with high and low sperm DNA fragmentation. We found that increased specific microbial profiles contribute to high sperm DNA fragmentation. In particular,
Lactobacillus iners
was uniquely correlated with high sperm DNA fragmentation. Additionally, butanoate may be the target metabolite produced by the microbiome to damage sperm DNA. Our findings support the interaction between semen microbiome and sperm DNA damage and suggest that seminal microbiome should be a new therapeutic target for HDFI patients.
Supplemental Material: Volcanic and orbitally forced carbon release during the Middle Eocene Climatic Optimum
Authors: ma yiquan , al. et
Published: June 2024

 Detailed geological setting, methods and results, host phases of mercury, error propagations for derivative proxies, evaluation of the negative carbon isotope excursion, and supplemental figures.  