bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of Total Hip Arthroplasty Combined With Hip Braces for Hip Charcot Arthropathy
Authors: Chao Long‐Teng , Zhuang Teng‐Feng , Huan Song‐Wei , Luo Si‐Min , Wu Chong‐Jie , Wu Wen‐Rui , Zha Zhen‐Gang , Zhang Huan‐Tian , Liu Ning
Published: December 2024

Objective

Charcot arthropathy is characterized by varying degrees of sensory loss and rapidly progressive joint destruction. Historically, limited studies indicated that Charcot arthropathy of the hip joint may be a contraindication for total hip arthroplasty (THA). Yet, some recent studies have shown that good clinical results and acceptable survival rate. Hence, this study aimed to investigate clinical outcomes, radiographic outcomes, complication rates and survivorship of primary THA in Charcot arthropathy.

Methods

We retrospectively included 11 patients (11 hips) with Charcot arthropathy who underwent THA between 1998 and 2016. All involved patients were diagnosed as syphilis. All patients had classic radiographic findings of Charcot arthropathy. The hip braces were used in all patients for six weeks after surgery. Outcome measures included VAS, Oxford Hip Score, and UCLA score. Statistical analyses involved t‐tests, chi‐square tests, and Kaplan–Meier survival analysis.

Results

The average follow‐up period was 81.73 months. The average VAS, Oxford Hip Score, and UCLA score were improved significantly. There was higher complication rate of 45.5% after THA. Reoperation was carried out in two patients due to dislocation and acetabular component loosening. The Kaplan–Meier survivorship with an end point of reoperation for any reason was 81.8%.

Conclusions

THA is proved to be reasonable in improving hip joint function, which is suitable for patients with Charcot hip joint. Although the complication rate is high, we consider that THA combined with hip brace may be a valid treatment choice for Charcot arthropathy with detailed preoperative planning and proper precautions.
Differential impact of impaired steryl ester biosynthesis on the metabolome of tomato fruits and seeds
Authors: López‐Tubau Joan Manel , Laibach Natalie , Burciaga‐Monge Alma , Alseekh Saleh , Deng Cuiyun , Fernie Alisdair R. , Altabella Teresa , Ferrer Albert
Published: December 2024

Steryl esters (SE) are a storage pool of sterols that accumulates in cytoplasmic lipid droplets and helps to maintain plasma membrane sterol homeostasis throughout plant growth and development. Ester formation in plant SE is catalyzed by phospholipid:sterol acyltransferase (PSAT) and acyl‐CoA:sterol acyltransferase (ASAT), which transfer long‐chain fatty acid groups to free sterols from phospholipids and acyl‐CoA, respectively. Comparative mass spectrometry‐based metabolomic analysis between ripe fruits and seeds of a tomato (Solanum lycopersicum cv Micro‐Tom) mutant lacking functional PSAT and ASAT enzymes (slasat1xslpsat1) shows that disruption of SE biosynthesis has a differential impact on the metabolome of these organs, including changes in the composition of free and glycosylated sterols. Significant perturbations were observed in the fruit lipidome in contrast to the mild effect detected in the lipidome of seeds. A contrasting response was also observed in phenylpropanoid metabolism, which is down‐regulated in fruits and appears to be stimulated in seeds. Comparison of global metabolic changes using volcano plot analysis suggests that disruption of SE biosynthesis favours a general state of metabolic activation that is more evident in seeds than fruits. Interestingly, there is an induction of autophagy in both tissues, which may contribute along with other metabolic changes to the phenotypes of early seed germination and enhanced fruit tolerance to Botrytis cinerea displayed by the slasat1xslpsat1 mutant. The results of this study reveal unreported connections between SE metabolism and the metabolic status of plant cells and lay the basis for further studies aimed at elucidating the mechanisms underlying the observed effects.
Exploring Disney's Worlds Through Religious Studies
Authors: Eichler‐Levine Jodi
Published: December 2024

Over the course of the last century (1923–2023), the Walt Disney Company has both catalyzed and reflected dizzying changes in the American cultural landscape—including religious ones. Scholars of Disney and religion often take one of three tactics to analyze this pairing: 1) Disney as religion 2) Disney depicting religion, or 3) Disney as influenced by religion. But all three of these ways of writing posit two separate, solid things called “Disney” and “religion; ” phenomena that meet and perhaps collide but remain distinct. This essay briefly reviews those methods, but it also thinks about the religious study of Disney through three other fluid, thematic approaches to the field: 1) Rituals, Spaces, Magic 2) Cultural Narratives, and 3) Corporate Forms and Disney Desires. In addition to summarizing prior research that is explicitly about Disney, I suggest how adjacent advances in religious studies can leads us to a nuanced study of what I will call the “Disney/religion nexus.” My goal is to expand, rather than reduce, the ways we think at this crossroads. This nexus fascinates precisely because it is not just Christianity, Buddhism, or Islam, nor is it Microsoft, Procter & Gamble, or Tesla. It has aspects of all these things, but it is something more. Disney is an assemblage of stories, people, places, and objects that don't fit into a traditional box, combining the religious flows people bring with them to Disney with the routinization and meaning making of this cultural titan.
Acceptability and feasibility of minimally invasive restorative procedures for patients with disability. A cohort study
Authors: Molina Gustavo F. , Zar Mariana , Ribba Laura , Mazzola Ignacio , Cabalén Maria Belén , Burrow Michael F.
Published: December 2024

Background

Unmet caries treatment needs are prevalent among people with disability, partly due to difficulties of cooperation during conventional dental treatment. This cohort study compared atraumatic restorative treatment (ART), silver modified atraumatic restorative treatment (SMART), and conventional restorative treatment (CRT), in terms of feasibility and acceptability in patients referred for special care dentistry in a specialized university clinic.

Methods

Patients referred for dental restorative care were treated using either ART, SMART, or CRT approach. Acceptance, feasibility, and complexity for the provision of care according to the BDA Case Mix Tool were assessed. ANOVA with Bonferroni correction and Chi‐square tests investigated differences in age, gender, and BDA scores. Spearman Logistic Regression was used to correlate treatment selection with BDA scores.

Results

From a total of 150 patients, 74 were included (20.6 ± 11.2 years of age) 26 chose ART, 35 SMART, 11 CRT and 2 were referred for sedation/GA. ART, SMART, and CRT were feasible for all patients who had selected these options, with optimal placement of restorations for all patients receiving ART, 95.8% of patients receiving SMART, and all patients receiving CRT. Local anesthesia was required for 4 of the 26 patients receiving ART and for the 11 patients receiving CRT, but not required for any of the patients receiving SMART (p = .001). BDA‐complexity scores were significantly higher for patients receiving SMART (OR 3.730, 95% CI 0.0∼1.82, p ≤ .001).

Conclusions

ART and SMART are feasible and acceptable approaches to restorative dental treatment in patients with a disability who have difficulty coping with conventional treatment. CRT is more likely to be selected by patients with lower BDA‐scores. The survival of the restorations should be assessed to determine the effectiveness of these options and further research is required to confirm the results of this pilot study in a larger population.
Using Self‐Reported Training Characteristics to Better Understand Who Is More Likely to Sustain Running‐Related Injuries Than Others: The Garmin‐RUNSAFE Running Health Study
Authors: Abrahamson Josefin , Lindman Ida , Eriksen Mathilde Birksoe , Kibsgaard Albert , Nielsen Rasmus Oestergaard
Published: December 2024

Running is a popular form of physical activity, yet it comes with risks, including running‐related injuries (RRIs). This cohort study aimed to use self‐reported baseline data on running experience, weekly running frequency, greatest running distance in 1 week, and running program to investigate if certain adult runners were more likely to sustain RRI than others. Runners, aged ≥ 18 years, familiar with the English language and using a Garmin watch to track their running were included. Running data and injury status were collected prospectively through the Garmin Connect application and weekly questionnaires over 18 months. Exposure variables were self‐reported running experience (years), weekly running frequency and distance, and use of structured running program (last 3 months before inclusion). The outcome was RRI. Time to event statistics was used to calculate cumulative risk differences (cRD) within groups of each exposure. Data were analyzed at 1000 km (km). A total of 7391 runners were included. The cumulative injury proportion was 57.8% [95% CI: 56.4%; 59.2%] after 1000 km. Those running > 105 km (cRD = −31.6, 95% CI −23.1; −40.1), 7 times per week (cRD = −47.1, 95% CI −35.9; −58.3) and followed a structured running program (cRD = 4.4; 95% CI 0.9; 7.8) had the fewest new RRIs. For running experience, those with few (< 1 years) or many years (> 40 years) of experience had the most RRIs. Runners were more prone to sustain an RRI if they had few (< 1) or many (> 40) years of running experience, lower total weekly running frequency (< 2 times/week), shorter weekly running distance (< 25 km), or did not use a structured running program.
HLA‐DRB1*14:270 and ‐DPA1*01:222 Identified by Next‐Generation Sequencing in Russian Bone Marrow Donors
Authors: Leonov Evgeny , Khamaganova Ekaterina , Kuzminova Elena , Khizhinskiy Stanislav , Parovichnikova Elena
Published: December 2024

Two novel alleles, HLA‐DRB1*14:270 and HLA‐DPA1*01:222, were discovered in Russian individuals.
Trainee Autonomy and Supervision in the Inpatient Clinical Learning Environment
Authors: Conner Stephanie M. , Choi Nancy , Fuller Jessica , Daya Sneha , Barish Peter , Rennke Stephanie , Harrison James D. , Narayana Sirisha
Published: December 2024

Background

Balancing autonomy and supervision during medical residency is important for trainee development while ensuring patient safety. In the increasingly complex inpatient clinical learning environment, tension exists when this balance is skewed. In this study, we aimed to understand current and ideal states of autonomy and supervision and then describe factors that contribute to imbalance from both trainee and attending perspectives.

Methods

A sequential mixed‐methods design included surveys and focus groups of trainees and attendings at three institutionally affiliated hospitals between May 2019 and June 2020. Survey responses were compared using t‐tests, chi‐square tests or Fisher's exact tests. Open‐ended survey and focus group data were analysed using thematic analysis.

Findings

Survey response rate was 42% (76/182) for trainees and 49% (101/208) for attendings. Fourteen trainees and 32 attendings participated in 14 focus groups. Trainees perceived current culture to be significantly more autonomous than attendings; both groups described ‘ideal’ culture as more autonomous than current state. Focus group analysis revealed five core contributors to the balance of autonomy and supervision: attending, trainee, patient, interpersonal and institutional. These factors were found to be complex and interactive and require frequent adjustment to avoid tension.

Conclusions

Trainees and attendings agree that resident autonomy should be prioritized more than it currently is. Attendings, trainees and patients contribute to a complex dynamic between autonomy and supervision, further impacted by both interpersonal and institutional factors, in the inpatient clinical learning environment. Capturing complex interactions between individual factors that impact this dynamic is critical to understanding and optimization by both trainees and attending.
Restorative Justice Practices as a Foundation for Medical Education Innovation
Authors: Klasson Christopher L. , Shibli‐Rahhal Amal , Ortiz Eric , Raghuram Ashrita , Behel Jay , Gregory Ada , Bernat Carrie , Castillo Nicole del
Published: December 2024

Background

Restorative justice (RJ) is an ethical lens that places emphasis on a community's connection and proliferative impact of actions, promoting communication and establishing methods for accountability. RJ practices can be applied on a spectrum, including proactive community‐building practices, community discussions in response to an event, and restorative conferences addressing specific incidences of harm. This article describes an intervention that utilized RJ community‐building practices within a medical education environment and evaluates its acceptability and feasibility.

Approach

During the summer of 2023, RJ interventions were planned, executed and assessed within two programmes involving pre–matriculant medical students, physician–assistant studies students and undergraduate students. The interventions utilized community‐building circles within small group activities. Capacity building included training for facilitators. Ninety‐five students participated in the RJ circles.

Evaluation

Evaluation included mixed methods pre‐ and post‐intervention surveys as well as qualitative interviews. Ten students (11%) responded to the pre‐intervention survey, and 17 responded to the post‐intervention survey (18%). Seven responses were obtained from interviews and qualitative surveys. Overall, participant survey responses indicated increased feelings of connection and perceptions of mutual understanding and that the programme provided adequate space to share one's perspective. Qualitative content analysis emphasized community building through RJ circles and their ability to promote connection, meaningful vulnerability, foster peer support and a desire to continue these activities.

Implications

RJ interventions within medical education environments are feasible and show considerable promise. Participants consistently noted the benefits of greater connection between peers, feelings of support and a desire for these practices to continue.
Galois groups of random polynomials over the rational function field
Authors: Entin Alexei
Published: December 2024

For a fixed prime power and natural number , we consider a random polynomial
with drawn uniformly and independently at random from the set of all polynomials in of degree . We show that with probability tending to 1 as the Galois group of over is isomorphic to , where is cyclic, and are small quantities with a simple explicit dependence on . As a corollary we deduce that as . Thus, we are able to overcome the versus ambiguity in the most natural restricted coefficients random polynomial model over , which has not been achieved over so far.
Optimizing Robotic Manipulation With Decision-RWKV: A Recurrent Sequence Modeling Approach for Lifelong Learning
Authors: Dong Yujian , Wu Tianyu , Song Chaoyang
Published: December 2024

Models based on the transformer architecture have seen widespread application across fields such as natural language processing (NLP), computer vision, and robotics, with large language models (LLMs) like ChatGPT revolutionizing machine understanding of human language and demonstrating impressive memory capacity and reproduction capabilities. Traditional machine learning algorithms struggle with catastrophic forgetting, detrimental to the diverse and generalized abilities required for robotic deployment. This article investigates the receptance weighted key value (RWKV) framework, known for its advanced capabilities in efficient and effective sequence modeling, integration with the decision transformer (DT), and experience replay architectures. It focuses on potential performance enhancements in sequence decision-making and lifelong robotic learning tasks. We introduce the decision-RWKV (DRWKV) model and conduct extensive experiments using the D4RL database within the OpenAI Gym environment and on the D’Claw platform to assess the DRWKV model’s performance in single-task tests and lifelong learning scenarios, showing its ability to handle multiple subtasks efficiently. The code for all algorithms, training, and image rendering in this study is available online (open source).
Quantum mechanics: A historical-linguistic perspective
Authors: Kragh Helge
Published: December 2024

Quantum mechanics would not be quantum mechanics without the many technical terms which emerged a century ago but are still found in modern textbooks. The theory was mainly created by German-speaking physicists, which is reflected in German–English hybrid words such as “eigenvalue” and “eigenstate.” While “eigenvalue” was a neologism—such as was “quantum mechanics” itself—other terms in the quantum lexicon were metaphors adopted from everyday language, e.g., “spin” and “tunneling.” Conversely, a few of the specialized quantum terms were later reused in common language with new meanings. In today's parlance, to make a “quantum jump” has a meaning entirely different from the one in which the expression originated. This paper examines various linguistic aspects associated with the early development of quantum mechanics and its predecessor, the old quantum theory. For example, all physicists are familiar with the quantum concept of degeneracy. But the same term has also been employed to denote certain groups of people as “degenerate.” Is there any historical connection between the two widely different connotations?
Decoherence, entanglement, and information in the electron double-slit experiment with monitoring
Authors: Strauch Frederick W.
Published: December 2024

This paper considers a theoretical model of the double-slit experiment with electrons whose paths are monitored. This monitoring, inspired by a recent text by Maudlin, is performed by the Coulomb scattering of the electron by a proton. A simple quantum mechanical calculation is presented, inspired in part by a recent experimental demonstration of this famous thought experiment. The results illustrate the relationship between entanglement and the loss of coherence in the interference pattern. The tradeoff between the visibility of interference and the information gained by measurement is also explored. This calculation can provide advanced undergraduates insight into decoherence, entanglement, and quantum information.
Quantum information science and technology high school outreach: Conceptual progression for introducing principles and programming skills
Authors: Schneble Dominik , Wei Tzu-Chieh , Kelly Angela M.
Published: December 2024

National data have shown the need to expand and diversify the talent pool of the quantum technologies workforce. This article describes a newly designed 25-h summer quantum information science and technology (QIST) program for high school students in grades 10–12; the goal is to advance physical science literacy and diversify the STEM pipeline through novel quantum science and quantum computing access and learning. This partnership between Stony Brook University and the New York Hall of Science was designed by quantum physicists and physics education researchers. This manuscript describes the rationale and progression of quantum ideas and computing skills introduced in the outreach program. The program design scaffolded physics, mathematics, and computer science concepts to engage high school students in the excitement of quantum information science and technology fields. The disciplinary content included the limitations of classical computing, classical and quantum physics principles (diffraction, polarization, wave-particle duality), the Mach–Zehnder interferometer, superposition, quantum thought experiments (Schrödinger's cat and Wigner's friend), entanglement and Bell's inequality, quantum key distribution, and basic quantum computing skills. Students also spent time visiting laboratories and museum exhibits and learning about academic progressions and career pathways in quantum technologies. This university-based science outreach model may be replicated by other quantum educators and adapted for learning in formal contexts.
Pressure estimation of ultra-high frequency ultrasound using gas vesicles
Authors: Strohm Eric M. , Wu Di , Malounda Dina , Nayak Rohit , Shapiro Mikhail G. , Kolios Michael C.
Published: December 2024

Acoustic microscopy uses ultra-high frequency (UHF) ultrasound transducers over 80 MHz to perform high-resolution imaging. The pressure output of these transducers is unknown, as commercial calibrated hydrophones can measure pressure for transducers with frequencies only up to 80 MHz. This study used gas vesicle nanostructures (GVs) that collapse at 571 kPa to estimate the pressure of UHF transducers at 40, 80, 200, and 375 MHz. Agarose phantoms containing GVs were made, and a baseline ultrasound image was performed at low pressure to prevent GV collapse. Sections within the phantom were scanned at varying voltage to determine the GV collapse threshold. The pressure at full driving voltage was then calculated, assuming a linear relation between transducer voltage and pressure. The pressure calculated for the 40 MHz transducer was 2.2 ± 0.1 MPa at 21 °C. Using a hydrophone, the measured pressure was 2.1 ± 0.3 MPa, a difference of <2%, validating the method at this frequency. The pressure calculated for the other transducers was 2.0 ± 0.1 MPa (80 MHz), 1.2 ± 0.1 (200 MHz), and 1.05 ± 0.17 (375 MHz at 37 °C). This study addresses the challenge of estimating pressure output from UHF ultrasound transducers, demonstrating that the pressure output in the 40–400 MHz frequency range can be quantified.
Genetic interaction analysis of
Candida glabrata
transcription factors
CST6
and
UPC2A
in the regulation of respiration and fluconazole susceptibility
Authors: Ollinger Tomye L. , Zarnowski Robert , Parker Josie E. , Kelly Steven L. , Andes David R. , Stamnes Mark A. , Krysan Damian J.
Published: December 2024

Candida glabrata
is the second most common cause of invasive candidiasis and is widely known to have reduced susceptibility to fluconazole relative to many other
Candida
spp. Upc2A is a transcription factor that regulates ergosterol biosynthesis gene expression under conditions of sterol stress such as azole drug treatment or hypoxia. Through an
in vitro
microevolution experiment, we found that loss-of-function mutants of the ATF/CREB transcription factor
CST6
suppresses the fluconazole hyper-susceptibility of the
upc2A
∆ mutant. Here, we confirm that the
cst6
∆
upc2A
∆ mutants are resistant to fluconazole but not to hypoxia relative to the
upc2A
∆ mutant. Sterol analysis of these mutants indicates that this suppression phenotype is not due to restoration of ergosterol levels in the
cst6
∆
upc2A
∆ mutant. Furthermore, increased expression of
CDR1
, the efflux pump implicated in the vast majority of azole-resistant
C. glabrata
strains, does not account for the suppression phenotype. Instead, our data suggest that this effect is due in part to increased expression of the adhesin
EPA3
, which has been shown by others to reduce fluconazole susceptibility in
C. glabrata
. In addition, we find that loss of both
UPC2A
and
CST6
reduces the expression of mitochondrial and respiratory genes and that this also contributes to the suppression phenotype as well as to the resistance of
cst6
∆ to fluconazole. These latter data further emphasize the connection between mitochondrial function and azole susceptibility.
A microaerobically induced small heat shock protein contributes to
Rhizobium leguminosarum
/
Pisum sativum
symbiosis and interacts with a wide range of bacteroid proteins
Authors: Domingo-Serrano Lucía , Sanchis-López Claudia , Alejandre Carla , Soldek Joanna , Palacios José Manuel , Albareda Marta
Published: December 2024

During the establishment of the symbiosis with legume plants, rhizobia are exposed to hostile physical and chemical microenvironments to which adaptations are required. Stress response proteins including small heat shock proteins (sHSPs) were previously shown to be differentially regulated in bacteroids induced by
Rhizobium leguminosarum
bv. viciae UPM791 in different hosts. In this work, we undertook a functional analysis of the host-dependent sHSP RLV_1399. A
rlv_1399-
deleted mutant strain was impaired in the symbiotic performance with peas but not with lentil plants. Expression of
rlv_1399
gene was induced under microaerobic conditions in a FnrN-dependent manner consistent with the presence of an anaerobox in its regulatory region. Overexpression of this sHSP improves the viability of bacterial cultures following exposure to hydrogen peroxide and to cationic nodule-specific cysteine-rich (NCR) antimicrobial peptides. Co-purification experiments have identified proteins related to nitrogenase synthesis, stress response, carbon and nitrogen metabolism, and to other relevant cellular functions as potential substrates for RLV_1399 in pea bacteroids. These results, along with the presence of unusually high number of copies of
shsp
genes in rhizobial genomes, indicate that sHSPs might play a relevant role in the adaptation of the bacteria against stress conditions inside their host.

IMPORTANCE

The identification and analysis of the mechanisms involved in host-dependent bacterial stress response is important to develop optimal
Rhizobium
/legume combinations to maximize nitrogen fixation for inoculant development and might have also applications to extend nitrogen fixation to other crops. The data presented in this work indicate that sHSP RLV_1399 is part of the bacterial stress response to face specific stress conditions offered by each legume host. The identification of a wide diversity of sHSP potential targets reveals the potential of this protein to protect essential bacteroid functions. The finding that nitrogenase is the most abundant RLV_1399 substrate suggests that this protein is required to obtain an optimal nitrogen-fixing symbiosis.
Positive regulation of a LuxR family protein, MilO, in mildiomycin biosynthesis
Authors: Li Zhiyu , Wang Yuli , Lin Chen , Wen Yu , Deng Zixin , Jiang Ming , He Xinyi
Published: December 2024

Mildiomycin is a representative peptidyl nucleoside antibiotic and was first isolated from
Streptoverticillium rimofaciens
, which has been used as an important biological agent to control powdery mildew in plants. Despite its importance, the biosynthetic pathways and regulatory mechanisms remain to be fully elucidated. In this study, we identified MilO as a positive pathway-specific regulator of mildiomycin biosynthesis in the heterologous host
Streptomyces avermitilis
. Gene disruption of
milO
resulted in almost loss of mildiomycin production, and it was restored to the level comparable to that in the wild-type strain in complemented strain. Overexpression of
milO
using host native promoter
rpsJ
p, engineered promotor
SP44,
and
kasO
p* led to a 50%, 6.5-fold, and 9.2-fold increase in mildiomycin production compared with the wild-type strain, respectively. Quantitative real-time PCR and electrophoretic mobility shift assay (EMSA) experiments revealed that MilO directly enhances the transcription of the
milA
gene by 20 folds after 48 h fermentation and indirectly regulates the transcription levels of other genes from
milB
to
milM
. Using DNase I footprinting assays,
milO
was revealed to bind to a 44 bp DNA sequence of the
milA
promoter region. The binding region consists of three imperfect direct repeats of TGTC(N)
3
CGGT separated by two-nucleotide spacers and each repeat is important to efficient binding to MilO. In addition, we identified two related compounds by overexpressing
milO
in a structural gene
milN
-deficient mutant. Taken together, this study indicates that pathway-specific regulator MilO is essential for mildiomycin biosynthesis and provides an effective strategy to improve the production of mildiomycin and its intermediates.

IMPORTANCE

As an important biological agent to control powdery mildew on plants, mildiomycin has been commercialized and used in various plants. However, its regulatory mechanisms and biosynthetic pathways remain unknown. This study provides new insights into the regulation of mildiomycin biosynthesis through MilO, a LuxR family protein that modulates mildiomycin production by directly enhancing the transcription of
milA
. The yield of mildiomycin was significantly improved by overexpressing
milO
in a heterologous host. In addition, the positive regulatory effect of
milO
helped to discover two related compounds, which provide important clues for the timing of uploading of two amino acid side chains during mildiomycin biosynthesis for the first time. In brief, our findings on transcriptional regulation of mildiomycin biosynthesis by
milO
will be valuable to further increase the yield of mildiomycin and explore its biosynthetic pathways.
Single-chain antibody gene therapy strategy based on high-throughput screening triggers sustained antiviral activity in the body
Authors: Zhao Liang , Wei Xue-Feng , Xu Kun , Zhao Zhao , Chen Guo , Wang Hou-Peng , Zhu Bin
Published: December 2024

The occurrence of viral diseases poses a huge threat and impact on human public health safety and the development of the animal and fishery industry. Here, a strain of single-chain antibody fragment, scFv-1, was isolated from the phage antibody display library construct by immunizing New Zealand white rabbits with rhabdovirus.
In vitro
analysis showed that the single-chain antibody could inhibit the infection of the virus in multiple pathways, including adsorption, fusion, and release.
In vivo
analysis revealed scFv-1 had a preventive and protective effect against the infection of virus. In addition, we describe that transposon-based transport of neutralizing genes allows for long-term, continuous expression, avoiding the need for lifelong, repeated passive immunization for treatment. In sum, high-throughput screening of neutralization genes based on phage display technology and transposon vector-based gene transfer provides effective methods for treating and preventing diseases and avoiding repetitive passive immunotherapy. This study also provides a reference for the prevention and treatment of unknown pathogens.

IMPORTANCE

Livestock and fisheries play an important role in economic development and food security. The frequent outbreaks of viral diseases have caused great losses to the livestock industry, while the increase in drug resistance caused by the use of antibiotics as well as the potential risks to human health have raised serious concerns. Here, we constructed a phage display antibody library by immunizing New Zealand white rabbits with purified rhabdovirus and selected a single-chain antibody, scFv-1, with good neutralizing activity, which was validated and found to be able to block multiple phases of the virus and thus play a neutralizing role. In addition, we describe that transposon-based transport of neutralizing genes allows for long-term, continuous expression, reducing the need for lifelong, repeated passive immunization for treatment. Our work not only provides methods for the prevention and treatment of viral diseases but also provides the body with long-lasting and even permanent protection against repeated passive immunization.
Complete genome of the mutualistic symbiont
Buchnera aphidicola
AIST from a Japanese strain of the pea aphid
Acyrthosiphon pisum
Authors: Mizutani Masaki , Koga Ryuichi , Fukatsu Takema , Kakizawa Shigeyuki
Published: December 2024

The genome of
Buchnera aphidicola
National Institute of Advanced Industrial Science and Technology (AIST), an obligate bacterial endosymbiont from a Japanese strain of the pea aphid
Acyrthosiphon pisum
, was determined. The genome sequence provides valuable information for comparative and evolutionary aspects of the intimate insect-microbe mutualism.
Response of the gut microbiome and metabolome to dietary fiber in healthy dogs
Authors: Bhosle Amrisha , Jackson Matthew I. , Walsh Aaron M. , Franzosa Eric A. , Badri Dayakar V. , Huttenhower Curtis
Published: December 2024

Dietary fiber confers multiple health benefits originating from the expansion of beneficial gut microbial activity. However, very few studies have established the metabolic consequences of interactions among specific fibers, microbiome composition, and function in either human or representative animal models. In a study design reflective of realistic population dietary variation, fecal metagenomic and metabolomic profiles were analyzed from healthy dogs fed 12 test foods containing different fiber sources and quantities (5–13% as-fed basis). Taxa and functions were identified whose abundances were associated either with overall fiber intake or with specific fiber compositions. Fourteen microbial species were significantly enriched in response to ≥1 specific fiber source; enrichment of fiber-derived metabolites was more pronounced in response to these fiber sources. Positively associated fecal metabolites, including short-chain fatty acids, acylglycerols, fiber bound sugars, and polyphenols, co-occurred with microbes enriched in specific food groups. Critically, the specific metabolite pools responsive to differential fiber intake were dependent on differences both in individual microbial community membership and in overall ecological configuration. This helps to explain, for the first time, differences in microbiome-diet associations observed in companion animal epidemiology. Thus, our study corroborates findings in human cohorts and reinforces the role of personalized microbiomes even in seemingly phenotypically homogeneous subjects.

IMPORTANCE

Consumption of dietary fiber changes the composition of the gut microbiome and, to a larger extent, the associated metabolites. Production of health-relevant metabolites such as short-chain fatty acids from fiber depends both on the consumption of a specific fiber and on the enrichment of beneficial metabolite-producing species in response to it. Even in a seemingly homogeneous population, the benefit received from fiber consumption is personalized and emphasizes specific fiber-microbe-host interactions. These observations are relevant for both population-wide and personalized nutrition applications.
Comparison of positive BioFire FilmArray meningitis/encephalitis (ME) panels, CSF cultures, CSF parameters, clinical presentation and in-patient mortality among patients with bacterial and fungal meningitis
Authors: Myint Thein , Soria Jaime , Gao Yuanzheng , Conejo Castillo Marice Ruiz , Arora Vaneet , Ribes Julie A.
Published: December 2024

The BioFire FilmArray meningitis/encephalitis panel (MEP) was brought to the University of Kentucky in 2016 to aid in the identification of community-acquired meningitis and encephalitis (ME). This panel has shown variable performance with some institutions showing high sensitivity and specificity for many pathogens but others seeing false positives during clinical use. We evaluated the panel’s performance using retrospective chart review of patients at the University of Kentucky from October 2016 to September 2022, including 7,551 MEP results. Cerebrospinal fluid (CSF) samples with positive results for bacterial and fungal pathogens were compared with CSF and blood cultures, other laboratory parameters, and clinical presentations, to classify MEP results as true positive (TP), likely TP, or false positive (FP). Of 132 patients with positive bacterial or fungal MEP results, 48.9% of bacterial and 88.9% of cryptococcal analytes were classified as TP. The positive predictive value (PPV) varied by organism, with the highest being
Listeria monocytogenes
and
Neisseria meningitidis
. One-third of the FP results were
Streptococcus agalactiae
. Among patients with likely TP, 75.7% (28 out of 37) received oral or IV antibiotics before blood or CSF culture. MEP was 100% specific compared to culture. The PPV based on pathogen ranged from 78.6% to 100%. Interestingly, 27.4% (29 out of 106) cases (excluding FPs) would have no pathogen definitively identified if MEP had not been used. This study highlights the utility of MEP in rapidly diagnosing ME, particularly in patients pretreated with antibiotics. It also emphasizes the importance of correlating MEP results with clinical assessments and other diagnostic tests to assure accuracy.

IMPORTANCE

This study compares the performance of the meningitis/encephalitis panel (MEP) in detecting bacterial and fungal pathogens with cerebrospinal fluid cultures and other parameters. Almost half of bacterial analytes of MEP had positive cerebrospinal fluid (CSF) or blood cultures; the remaining 42% of bacterial analytes were correlated with clinical presentation and other CSF parameters. 27.4% (29 out of 106) cases would not have had a pathogen definitively identified if the MEP had not been used. This study highlights the importance of using MEP as a diagnostic tool, especially in patients who have already received antibiotics, where traditional culture-based methods may not be diagnostic. This research underscores the use of MEP in improving the speed of diagnosing meningitis. However, it emphasizes that MEP can produce false positive results in some patients. It is therefore necessary to interpret MEP results together with clinical assessments and other diagnostic tests to ensure the most accurate diagnosis.
Data sharing in circadian rhythm and mental health research: current status, challenges, recommendations and future directions.
Authors: Deeb Haya , Zieliński Tomasz , Millar Andrew J
Published: December 2024

Data sharing is a cornerstone of modern scientific research, playing a critical role in fostering greater collaboration, enhancing reproducibility, transparency and efficiency of scientific discoveries, and integrating diverse data sources. In circadian rhythm research, data sharing is particularly important due to the complexity and heterogeneity of the data, which includes molecular profiles, physiological measurements, clinical data and sensor-based data. UK research funders, such as Medical Research Council, Wellcome Trust and UK Research and Innovation, have established data-sharing policies to promote open science and enhance research transparency. Despite these policies, a recent assessment within the UK Circadian Mental Health Network (CMHN), which incorporates an analysis of publications from several countries, revealed that data sharing remains limited. Significant challenges including data complexity, privacy and ethical considerations, technical issues and entrenched academic culture are major barriers to progress. This perspective article highlights the current state of data sharing in circadian and mental health research, identifies key obstacles and compares these practices with broader trends. We also provide insights from principal investigators within the CMHN on the reasons for limited data sharing. To address these challenges, researchers can foster a culture of openness by seeking training, planning ahead in ethics processes and data management plans and using data outputs in research assessment. We outline CMHN’s future plans to deliver training on Findable, Accessible, Interoperable, Reusable principles, offer data curation services and provide ethical guidelines. By adopting these strategies, we aim to improve data-sharing practices, ultimately advancing our understanding of circadian rhythms and their implications for mental health.
Effectiveness of nutritional education intervention during pregnancy on birth outcomes in sub-Saharan Africa: a protocol for a systematic review and meta-analysis
Authors: Shibiru Shitaye , Jerene Degu , Mersha Abera , Ayele Gistane , Belachew Tefera
Published: December 2024

Introduction

Nutritional education intervention during pregnancy is the process of teaching pregnant women about the importance of a healthy diet and how to make healthy food choices. It is an important part of public health and vital to preventing adverse birth outcomes. Therefore, synthesising available evidence on the effect of nutritional education intervention on birth outcomes is essential for decision-making by policymakers and for identifying needed gaps for future research.

Objective

To systematically collect, review and summarise available evidence on the pooled effect of the nutrition education to pregnant women on birth outcomes in sub-Saharan Africa.

Primary and secondary outcome measures

The primary outcome measures will be birth outcomes, while maternal outcomes will be treated as secondary.

Methods and analysis

This systematic review will systematically search and collect data from a variety of databases, including the MEDLINE, CINAHL, EMBASE, Joanna Briggs Institute Database, Cochrane Database, PEDro, POPLINE, ProQuest, OpenGrey (SIGLE), Google Scholar, Google, APA PsycINFO, Web of Science, Scopus and HINARI. In addition, the systematic review will also search for unpublished studies and grey literature from a variety of sources. The review will only include experimental and quasi-experimental studies published in English from 1 January 2013 to 31 December 2023. Two independent reviewers will critically appraise all eligible studies for methodological quality using the standard Joanna Briggs Institute (JBI) Critical Appraisal Checklist for randomised controlled trials. Any disagreements between the reviewers will resolve through discussion. Either a random effects or fixed effects model will be used to pool the data, depending on the appropriateness of the model. The heterogeneity will be assessed statistically using the standard χ² and I2tests. Publication bias will be examined graphically using funnel plots and statistically using Egger’s regression test. In the case when funnel plot is asymmetric and/or Egger’s test is statistically significant, the trim and fill (Duval and Tweedie’s) analysis will be performed. Statistical association between independent and dependent variables will be declared at p<0.05. The meta-analysis will be conducted using the statistical software STATA V.17.

Ethics and dissemination

By synthesising existing research without ethical concerns, this impactful review will be published and presented across academic and relevant institutions.

PROSPERO registration number

CRD42023473371.
Contextual factors influencing the use of digital health by patients and physicians in primary care: a scoping review protocol
Authors: Luchowska Katarzyna , Chmielewska Małgorzata , Byszek Katarzyna , Olearczyk Agata , Gawrońska Anna , Więckowska Barbara
Published: December 2024

Introduction

Integrating digital health technologies to improve the overall performance of healthcare systems counts among the top priorities of the WHO. As evidenced in recent research, there are specific factors that may decisively determine the effective implementation and development of innovative digital health solutions. This review attempts to recognise and map the existing body of research and evidence to identify the determinants that either favour or hinder the deployment and use of digital health technologies by patients and physicians in primary care.

Methods and analysis

The scoping review will be conducted in accordance with the JBI Manual for Evidence Synthesis (2024 edition introducing nine stages) and with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. Search strategy will be conducted in PubMed, Embase, Cochrane Database of Systematic Reviews and Scopus in November 2024. The review will include quantitative, qualitative, mixed-methods studies, systematic, scoping or umbrella reviews, as well as text and opinion papers. The study selection process will be conducted by two researchers using Rayyan. The data will be analysed using MAXQDA and extracted into a tool prepared by the researchers. This review will summarise the existing data and will help create a list of potential and determinant barriers and facilitators that may be useful in conducting empirical research on embedding new digital health solutions and sustaining their use.

Ethics and dissemination

As no primary data will be collected for the purposes of this study, no formal ethical approval is required. Results will be published in a peer-reviewed journal. The findings will be used to conduct further research (HORIZON.2.1;grant:101095424) on the determinants of digital health implementation in primary care at the national level and to prepare recommendations for key stakeholders, as well as to develop recommendations on health policy in the European Union.
Mailed smoking cessation support for Aboriginal and Torres Strait Islander people who smoke: protocol for a hybrid type 1 effectiveness – implementation trial
Authors: Bryant Jamie , Roberts-Barker Kayden , Mills Zabowie , Booth Kade , Foster Joley , Mersha Amanual Getnet , Maddox Raglan , Chamberlain Catherine , Bonevski Billie , Segan Cathy , Taylor Nathan , Kennedy Michelle
Published: December 2024

Introduction

Smoking is the leading preventable cause of death and the single most significant risk behaviour contributing to adverse health conditions among Aboriginal and Torres Strait Islander people. There is an urgent need for innovative approaches to support reductions in smoking prevalence. This study will assess the implementation and effectiveness of a mailed smoking cessation support programme that includes nicotine replacement therapy (NRT) (Which Way Quit Pack) for Aboriginal and Torres Strait Islander people.

Methods and analysis

A hybrid type 1 effectiveness—implementation trial will be conducted in Australia from 2023 to 2025. A sample of 500 Aboriginal and Torres Strait Islander people aged over 16 who smoke will be recruited using social media. All participants will: (a) receive a mailedWhich Way Quit Packthat includes pamphlets and resources on quitting, information about quit smoking support options (MyQuitBuddy App) and a selection of merchandise; (b) be offered a referral to Aboriginal Quitline; and (c) be offered a free 12-week mail out course of combination NRT. Outcome data will be obtained using quantitative surveys and qualitative Yarning. Effectiveness outcomes will include assessment of 7-day point prevalence, continuous abstinence and quit attempts at 3- and 6-month follow-up. Implementation outcomes will include assessment of recruitment and retention rates, intervention uptake and adherence, and intervention acceptability.

Cessation data will be analysed using an intention-to-treat principle with all individuals lost to follow-up considered as smoking. Yarns will be analysed by Aboriginal and Torres Strait Islander members of the research team privileging Collaborative Yarning, with the support of a reflexive thematic analysis approach that will identify themes while also reflecting potential biases and perspectives of the researcher throughout the analysis process.

Ethics and dissemination

Ethics approvals were obtained from Aboriginal Health and Medical Research Council Ethics Committee of NSW (1894/21) and the University of Newcastle (H-2022-0174). Findings will be disseminated through publications, conference presentations and sharing with relevant government bodies.

Trial registration number

Australian New Zealand Clinical Trials Registry (ACTRN12623001021662).