bluuebunny/crossref_metadata_2025 huggingface dataset:
Major role of dolutegravir in the emergence of the S147G integrase resistance mutation
Authors: Wirden Marc , Abdi Basma , Lambert-Niclot Sidonie , Chaix Marie-Laure , De Monte Anne , Montes Brigitte , Pallier Coralie , Bellecave Pantxika , Bouvier-Alias Magali , Raymond Stephanie , Yerly Sabine , Charpentier Charlotte , Calvez Vincent , Descamps Diane , Marcelin Anne-Genevieve
Published: December 2024

Background

The S147G mutation is associated with high-level resistance to the integrase strand transfer inhibitor (INSTI) elvitegravir. In several poorly documented cases, it was also selected in patients on dolutegravir. Given the widespread use of dolutegravir, further studies of S147G are required.

Methods

We consulted the HIV-1 resistance databases of French laboratories to identify all cases of S147G emergence. We collected immunological and virological parameters, history of treatment and INSTI resistance mutations. Mann–Whitney and Fisher’s exact tests were performed.

Results

We retrospectively identified 88 cases of S147G selection, from 2015 to 2022, in 22 laboratories. The most frequent HIV-1 subtypes were Clade B (55.7%) and CRF02_AG (21.6%). At the time of resistance genotyping, the median viral load was 5860 copies/mL (IQR 1011–24  525) and the median CD4 cell count was 412 cells/mm3 (228–560). S147G emerged on dolutegravir (48%), elvitegravir (36%) and raltegravir (10%) treatments. S147G was associated with a larger median number of other INSTI mutations on dolutegravir than on elvitegravir [3.0 (2.0–4.0) versus 2.0 (1.0–2.0); P = 0.0002] and was never observed with Q148H or G118R. On dolutegravir, S147G was associated principally with T97A (62%), N155H (59%), E138K (50%), L74I/M (38%) and Q148R (33%).

Conclusions

In this French study, S147G emerged principally in patients on dolutegravir regimens, in association with up to five other INSTI resistance mutations. This accumulation of mutations suggests a replicative advantage on HIV strains under dolutegravir selection pressure, suggesting that caution is required when interpreting dolutegravir resistance in the presence of such S147G resistance patterns, even in patients prescribed dolutegravir twice daily.
Molecular characterization of antibiotic resistance in bacteria from daycare centres in Ile-Ife, Nigeria
Authors: Wilkie Eunice Damilola , Alao Jude Oluwapelumi , Thonda Oluwakemi Abike , Oluduro Anthonia Olufunke
Published: December 2024

Background

Antibiotic resistance is an escalating global health issue, with particularly severe implications in low- and middle-income countries (LMICs) such as Nigeria. This study examines antibiotic-resistant bacteria’s prevalence and molecular characteristics in daycare centres in Ile-Ife, Nigeria, where high antibiotic use and limited infection control measures present significant challenges.

Methods

Between November 2017 and July 2019, samples were collected from 20 daycare centres, including swabs from fomites and children. Bacterial isolates were identified and assessed for antibiotic susceptibility using standard methods. Molecular techniques, including PCR, were employed to detect resistance genes such as blaSHV, tetA, dfr1 and mecA.

Results

The study found high resistance levels among common pathogens, with S. aureus and other staphylococci showing significant resistance to ampicillin and Augmentin and Gram-negative bacteria exhibiting broad resistance patterns. Resistance genes, including blaSHV and mecA, were identified in multiple isolates, indicating the spread of crucial resistance mechanisms.

Conclusions

The results highlight the critical need for improved surveillance, targeted antimicrobial stewardship and enhanced infection control practices in daycare centres to address the growing threat of antibiotic resistance. This research offers valuable insights into resistance dynamics in paediatric settings and supports the development of strategies to manage the spread of resistant bacteria in LMIC contexts.
Algorithmic individual fairness and healthcare: a scoping review
Authors: Anderson Joshua W , Visweswaran Shyam
Published: December 2024

Objectives

Statistical and artificial intelligence algorithms are increasingly being developed for use in healthcare. These algorithms may reflect biases that magnify disparities in clinical care, and there is a growing need for understanding how algorithmic biases can be mitigated in pursuit of algorithmic fairness. We conducted a scoping review on algorithmic individual fairness (IF) to understand the current state of research in the metrics and methods developed to achieve IF and their applications in healthcare.

Materials and Methods

We searched four databases: PubMed, ACM Digital Library, IEEE Xplore, and medRxiv for algorithmic IF metrics, algorithmic bias mitigation, and healthcare applications. Our search was restricted to articles published between January 2013 and November 2024. We identified 2498 articles through database searches and seven additional articles, of which 32 articles were included in the review. Data from the selected articles were extracted, and the findings were synthesized.

Results

Based on the 32 articles in the review, we identified several themes, including philosophical underpinnings of fairness, IF metrics, mitigation methods for achieving IF, implications of achieving IF on group fairness and vice versa, and applications of IF in healthcare.

Discussion

We find that research of IF is still in their early stages, particularly in healthcare, as evidenced by the limited number of relevant articles published between 2013 and 2024. While healthcare applications of IF remain sparse, growth has been steady in number of publications since 2012. The limitations of group fairness further emphasize the need for alternative approaches like IF. However, IF itself is not without challenges, including subjective definitions of similarity and potential bias encoding from data-driven methods. These findings, coupled with the limitations of the review process, underscore the need for more comprehensive research on the evolution of IF metrics and definitions to advance this promising field.

Conclusion

While significant work has been done on algorithmic IF in recent years, the definition, use, and study of IF remain in their infancy, especially in healthcare. Future research is needed to comprehensively apply and evaluate IF in healthcare.
Recycling honey bee drone brood for sustainable beekeeping
Authors: Pavlović Ratko , Crailsheim Karl , Petrović Miloš , Goessler Walter , Zarić Nenad M
Published: December 2024

Pollination by insects is vital for global agriculture, with honey bees (Apis mellifera L.) being the most important pollinators. Honey bees are exposed to numerous stressors, including disease, pesticides, and inadequate nutrition, resulting in significant colony losses. This study investigates the use of drone brood to mitigate these problems. Drone brood, which is normally discarded during varroa mite (Varroa destructor, Anderson and Trueman) management, is rich in proteins, fats, and essential minerals. We compared drone brood with an already suggested pollen supplement (Tenebrio [Tenebrio molitor L.] flour). The results indicate that drone brood flour is a viable source of proteins, fats, and minerals and is potentially antimicrobial due to its high content of elements with known antimicrobial properties. It meets the nutritional needs of honey bees while mitigating the effects of varroa mites. The use of drone brood flour can provide high-quality beeswax, surplus of pollen, and improve bee health, which promotes sustainable beekeeping.
Bernard Greenberg: a legacy in medical, veterinary, and forensic entomology
Authors: McNeal Rachel , Wells Jeffrey D , Tomberlin Jeffery K
Published: December 2024

Bernard Greenberg was a ground-breaking scientist in the worlds of medical-veterinary and forensic entomology, studying the ability of flies to serve as a vector of human and other vertebrate pathogens. His work also extended beyond these topics, creating key studies on flies and their associated microbial ecology. These efforts led to numerous research publications and two books on flies and their associated microorganisms. Greenberg served a pioneering role in establishing the field of forensic entomology in the USA later in his career, publishing key papers and a book that are highly cited to this day. We present a review of Dr Greenberg’s scientific contributions concerning flies and disease, insect/microbe interactions, and insects as forensic indicators.
Basic properties of solidified organic liquids at a cryogenic temperature for electron microscopic visualization and sample preparation of dispersion systems
Authors: Okada Satoshi
Published: December 2024

It is challenging to image structures in liquids for electron microscopy (EM); thus, low-temperature imaging has been developed, initially for aqueous systems. Organic liquids (OLs) are widely used as dispersants, although their cryogenic EM (cryo-EM) imaging is less common than that of aqueous systems. This is because the basic properties (e.g. vapor pressure, density and amorphousness) of OL in the solid state have not been extensively investigated, preventing the determination of whether the observed structure is free from artifacts. Herein, I summarized physical data related to the phase change, and the solid density at 77 K and sublimation speed for some OLs were measured independently to discuss the applicability of OLs for cryo-EM. Among various OL properties, the sublimation temperature, pressure and rate and crystallinity are important for cryo-EM. The sublimation-related properties are used to judge whether the OL is stable during storage, observation and sample preparation such as etching. These properties were calculated, and the calculated sublimation speed matched with that measured by cryogenic scanning EM movie imaging. Crystallinity was estimated using the difference between the extrapolated temperature-dependent liquid density and the solid density of frozen OLs measured in liquid nitrogen. Artifacts observed upon freezing were exemplified by focused ion beam cross-sections of OL-in-water emulsions, and cracks, voids and wrinkles are found in the OL phase at a large shrinkage ratio. The study findings show that the applicability of OLs largely differs for structural isomers and that appropriate OLs are required for the cryo-EM imaging of nonaqueous systems.
Time-varying correlations in multivariate unobserved components time series models
Authors: Schiavoni Caterina , Koopman Siem Jan , Palm Franz , Smeekes Stephan , van den Brakel Jan
Published: December 2024

Multivariate unobserved components time series models can accommodate dynamic relations between dependent variables by introducing nonzero correlations between the disturbances that drive the dynamics of the components. The usual assumption of time-invariant correlations can be rather strong for many applications. In this study, we introduce a time-varying correlation parameter that allows the dynamic relations to change over time. We treat the parameter as a dynamic unobserved component. The resulting nonlinear model requires nonlinear methods for parameter estimation and filtering. For parameter estimation, we propose an indirect inference approach based on an auxiliary model using a cubic spline for the time-varying correlation. For the filtering of the time-varying correlation, a bootstrap filter is employed jointly with the technique of Rao–Blackwellization. A Monte Carlo simulation study shows that our proposed methodology is successful in both estimation and filtering. In our empirical study, we explore the strong dependence between monthly unemployment in the labour force and claimant counts. We find strong evidence that the underlying correlations are time-varying.
The association between difficult-to-treat rheumatoid arthritis and probable sarcopenia
Authors: Ohashi Yoshifumi , Suzuki Mochihito , Sobue Yasumori , Terabe Kenya , Asai Shuji , Takahashi Nobunori , Imagama Shiro
Published: December 2024

Objectives

To identify factors associated with probable sarcopenia in patients with rheumatoid arthritis (RA).

Methods

Probable sarcopenia was diagnosed using the SARC-F questionnaire. Patients with difficult-to-treat RA (D2T-RA) were defined as those with a history of using ≥2 biological/targeted synthetic (b/ts) disease-modifying antirheumatic drugs (b/tsDMARDs) who had moderate or high disease activity. Among 486 patients, 101 were classified into the probable sarcopenia group (SARC-F ≥4), and 385 were classified into the non-probable sarcopenia group (SARC-F <4). Factors associated with probable sarcopenia were examined using multiple logistic regression analysis. Additionally, patients were divided into the D2T-RA (n = 38) and non-D2T-RA (n = 448) groups, and the proportion of probable sarcopenia and RA treatment status were compared.

Results

Factors associated with probable sarcopenia included age [adjusted odds ratio (OR): 1.03], body mass index (OR: 1.16), D2T-RA (OR: 3.39), and Health Assessment Questionnaire-Disability Index (OR: 1.38), and diabetes mellitus (OR: 2.77). The proportion of probable sarcopenia was significantly higher (60.5% vs. 17.4%), and the rate of methotrexate use was significantly lower (34.2% vs. 64.1%), in the D2T-RA group than in the non-D2T-RA group. Moreover, in the D2T-RA group, most patients used two or three b/tsDMARDs (two: 68.4%, three: 21.1%).

Conclusions

D2T-RA was associated with probable sarcopenia. Tight control by treatment enhancement may help overcome sarcopenia.
Effect of Plant-Based Diets on Rheumatoid Arthritis: A Systematic Review
Authors: Bostan Zekiye Zeynep , Şare Bulut Melike , Özen Ünaldı Buket , Albayrak Buhurcu Ceren , Akbulut Gamze
Published: December 2024

Context

Rheumatoid arthritis (RA) is an autoimmune disease that leads to chronic inflammation and joint damage. Various plant-based diets are thought to have effects on RA symptoms and disease activity.

Objective

Relevant literature on the effect of different types of plant-based diets on RA was reviewed.

Data Sources

A systematic search was conducted using the Web of Science, PubMed, Scopus, and Cochrane databases and following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Data Extraction

Articles on observational and interventional human studies carried out in the adult population and published in English between February 2013 and April 2023 were eligible for inclusion. Articles reporting on studies performed in populations under 18 years of age, with unclear methods and results, or for which the full text was unavailable were excluded. The risk of bias in the selected studies was assessed using the Joanna Briggs Institute checklists.

Data Analysis

Of 547 screened articles, 15 were included, comprising 4 cross-sectional, 2 cohort, and 9 randomized controlled trials. These studies examined the effects of various diets, including the Mediterranean, low-fat high-carbohydrate, anti-inflammatory, and vegan, on RA. Results indicate adherence to plant-based diets generally reduced disease severity and improved dietary intake, physical activity, body weight, and key clinical markers such as the Disease Activity Score-28, Visual Analog Scale score, Health Assessment Questionnaire Disability Index, erythrocyte sedimentation rate, and C-reactive protein level in patients with in RA.

Conclusions

Most of the studies suggested the Mediterranean diet may positively affect the severity of RA. However, the included studies show heterogeneity. Therefore, more randomized controlled studies are needed in this area to increase understanding of the effect of diet on RA and facilitate the implementation of strategies to prevent RA.

Systematic Review Registration

PROSPERO registration no. CRD42023420577.
One Health Field Approach Applied to Leptospirosis: A Systematic Review and Meta-Analysis Across Humans, Animals and the Environment
Authors: Antoniolli Andrea , Guis Hélène , Picardeau Mathieu , Goarant Cyrille , Flamand Claude
Published: December 2024

Background

Leptospirosis is a neglected zoonosis transmitted through urine of infected hosts or contaminated environments. The transmission of bacteria between humans, animals, and the environment underscores the necessity of a One Health approach.

Methods

We conducted a systematic review to identify significant findings and challenges in One Health research on leptospirosis, focusing on studies involving sampling in ≥2 of the 3 compartments: human, animal, and environment. We searched in PubMed, Web of Science, Medline, Scopus, and ScienceDirect from 1 January 1918 to 31 December 2022. We assessed risk of bias in studies using Joanna Briggs Institute tools and performed a meta-analysis to identify links between One Health compartments.

Results

Of 1082 leptospirosis studies with sampling, 102 multicompartmental studies conducted between 1972 and 2022 were included: 70 human-Animal, 18 animal-environment, 4 human-environment, and 10 across all compartments. Various methodological weaknesses were identified, from study design to statistical analysis. Meta-regressions identified positive associations between human and animal seroprevalences, particularly with livestock and with wild nonrodent animals, and a link between the environmental positivity rate and domestic animal seroprevalence. Our analysis was constrained by the limited number of studies included and by the quality of protocols.

Conclusions

This 50-year overview of One Health field approach to leptospirosis highlights the critical need for more robust, well-supported One Health research to clarify the transmission dynamics and identify risk factors of zoonoses.
Exploring the formation and permeability of plasmodesmata in the liverwort, Marchantia polymorpha
Authors: Hsu Chia-Yun , Hsu Chia-Hsuan , Chang Hui-Yu , Lu Kuan-Ju
Published: December 2024

Plasmodesmata are cell-wall-embedded channels that evolved in the common ancestor of land plants to increase cell-to-cell communication. Whether all the fundamental properties of plasmodesmata emerged and were inherited in all land plants at the same time is unknown. Here, we show that the bryophyte Marchantia polymorpha (a nonvascular plant) forms mostly simple plasmodesmata in early-developing gemmae. The complexity of plasmodesmata increases during gemma maturation, and complex plasmodesmata with enlarged cavities are majorly observed in thalli. In contrast to vascular plants, whose simple plasmodesmata can transport monomeric fluorescent proteins, plasmodesmata in M. polymorpha limited their permeability before the juvenile-to-adult transition. In support, callose, a known polysaccharide regulating plasmodesmata permeability in vascular plants, accumulated in most of the M. polymorpha tissues examined. Furthermore, we found that in the apical meristematic region, plasmodesmata allowed the transport of monomeric fluorescent proteins, and this relaxation might correlate with the lower accumulation of callose. Taken together, our study suggests that certain plasmodesmata properties, such as complexity progression and callose accumulation, may have evolved before the divergence between vascular and nonvascular plants.
Federalism and Social Policy Expansion in Canada during the Justin Trudeau Era
Authors: Dinan Shannon , Béland Daniel
Published: December 2024

Canadian federalism entrusts subnational entities with responsibility over most social policy areas. Yet, the federal government wields influence over social policy through different institutional paths, including the ability to spend in policy areas located outside its jurisdiction. In this article, we analyze the relationship between federalism and social policy during the successive Justin Trudeau Liberal governments by examining key areas that have witnessed expansion, including childcare, pensions, and health care. Illustrating all three models of federal-provincial social policy relations identified by Banting (2005), these policy areas feature varied institutional configurations that point to the diversity of the relationship between federalism and social policy expansion in Canada. Building on the work of Graefe and Fiorillo (2023), we show that—despite communicating a desire for collaboration and cooperation—the Trudeau governments have advanced a top-down federal social policy agenda in key policy areas.
Working from Home and Parental Childcare Division: Evidence from Two Years of the COVID-19 Pandemic
Authors: Boll Christina , Müller Dana , Osiander Christopher , Schüller Simone
Published: December 2024

We investigate the dynamics of gendered parental childcare division across the coronavirus disease 2019 pandemic up until spring 2022. We employ unique data from a German (bi)monthly survey based on a random sample from administrative data (IAB-HOPP) and find dynamics toward a more equal division. Up to April 2021, drivers are couples with already care-involved fathers, while later on, couples with a strongly traditional division drive these changes. The latter shift emerges in parental constellations where fathers unilaterally gain working-from-home possibilities. Our results give moderate support for optimism but also point to an ambiguous role of working from home.
Establishing a baseline for comparing classroom discourse from representative geometry lessons: pivotal teaching moments and cognitive levels of student discourse
Authors: Joswick Candace , Kribs Christopher M , McDonald Evangeline
Published: December 2024

Pivotal teaching moments (PTMs), when a student says something unanticipated by the teacher, offer key opportunities to shape learning and student discourse in a lesson, so studying teachers’ responses to them yields important descriptors of pedagogy and its impact on student mathematical thinking. Recent decades have seen developments in research on, and standards for, classroom mathematics, but no comprehensive examination of changes in the ways teachers respond to student discourse. This sequential mixed-methods study applies our novel framework for analyzing elements of PTM episodes to all available English-language Third International Mathematics and Science Study geometry lesson videos, as a first step to establishing a baseline description of mathematics teachers’ discourse practices in the 1990s. We find many of the PTMs stemmed from students’ incorrect mathematical statements, and the dominant teacher response focused on emphasizing correct answers and meanings rather than pursuing student thinking, with relatively low-cognitive-level student discourse ensuing. Discourse patterns are especially significant in geometry, where research has seen students struggle to articulate their understanding.
First report of hop stunt viroid infecting luffa and cantaloupe in Taiwan
Authors: Cheng Ying-Huey , Lin Tsung-Chun , Lin Mei-Ju , Lin F.-C. , Wang Jau-Yueh , Kuo Chang-Hsin , Chiang C.-H.
Published: December 2024

Luffa (Luffa cylindrica (L.) M. Roem.) and cantaloupe (Cucumis melo L.) are economically important cucurbitaceous crops in Taiwan. In August 2018, luffa samples displaying leaf chlorosis and deformation were collected in Nantou while cantaloupe samples exhibiting the above suspected systemic viral-like symptoms were collected in Chiayi in October 2019, respectively. Reverse transcription (RT)-PCR tests were conducted to investigate potential viral infections in leaf samples from 12 luffa and nine cantaloupe plants. Total nucleic acids were extracted from symptomatic cucurbit tissues using the taco™ DNA/RNA extraction kit (GeneReach Biotechnology, Taiwan), followed by PCR or RT-PCR tests for virus detection. Seven sets of degenerate primers targeting viral genera reported in local cucurbit crops, including genera Begomovirus, Crinivirus, Cucumovirus, Polerovirus, Potyvirus, Orthotospovirus and Tobamovirus, were utilized. However, all tests yielded negative results. Consequently, degenerate primers targeting genus Pospiviroid or hop stunt viroid (HSVd)-specific primers were employed. Among these tests, only HSVd-specific primers HSVd-RTR_F/R (5’-GGAATTCTCGAGTTGCCGCA-3’/5’-CCGCGGCCCTCTCT-3’) (van Dorst and Peters 1974) successfully amplified DNA fragments of approximately 130 bp from 19 symptomatic samples (12 from luffa and 9 from cantaloupe), while normal leaf samples of luffa and cantaloupe tested negative. Based on known nucleotide sequences, primers were designed to amplify and obtain the full-length 303-nucleotide sequences of the HSVd genome derived from luffa (accession no. OP331278) and cantaloupe (accession no. OP331279). The two sequences exhibit a 98.7% nucleotide identity with each other while exhibiting 99.3% nucleotide identity with a cucumber isolate from Japan (X00524) (Sano et al. 1984) and 98.0% nucleotide identity with another isolate (X07405) from the Netherlands (Puchta et al. 1988). Comparisons with 13 HSVd citrus isolates from Taiwan revealed nucleotide similarities ranging from 96.1% to 99.0%. To confirm pathogenicity, Nicotiana benthamiana was chosen as the experimental isolation host. Mechanical inoculation of N. benthamiana with diluted sap (20 W/V) from diseased plants consistently produced leaf wrinkling and stunting symptoms in 10–60% of inoculated plants by 12 days post-inoculation (DPI). RT-PCR tests confirmed viroid infection. Additionally, luffa seedlings at the cotyledon stage back-inoculated with the purified HSVd luffa isolate developed leaf deformation symptoms 15–25 DPI, and the infection was confirmed by RT-PCR, fulfilling Koch’s postulates. HSVd infections have previously been reported in citrus and grapes in Taiwan (Lin et al. 2015). To our knowledge, this is the first report of HSVd infecting luffa and cantaloupe in Taiwan. The newly identified HSVd cucumber isolates represent a potential threat to cucurbit production and warrant further investigation.
Race and gender biases in assessing pain intensity and medication needs among Chinese observers
Authors: Liu Zhiyuan , Chuang Tzu-Ying , Wang Shan
Published: December 2024

Introduction:

Pain-related decision-making can be influenced by the caregiver and sufferer's demographic factors, such as race and gender, which are commonly considered individually. However, such factors may influence pain assessment interdependently based on caregivers' stereotypical beliefs.

Objectives:

This study investigated how sufferers' race and gender affect Chinese observers' evaluations of pain intensity and medication needs and the associations with the observers' race and gender-related stereotypical beliefs.

Methods:

One hundred sixty-two Chinese participants completed a pain facial expression rating task assessing the level of pain intensity and the extent to which they believe the sufferer needs pain medication for East Asian, White, and Black sufferers, followed by a battery of questionnaires measuring their gender and race role expectation of pain.

Results:

Chinese observers were more stringent on East Asians' pain intensity and needs for medication than Whites and Blacks'. However, when Black and East Asian sufferers were perceived to have a similar level of pain, East Asians were more likely to receive medication than Blacks, which is partly due to the observers' stereotypical beliefs that Blacks would have a speedier recovery than East Asians.

Conclusions:

Our results provided evidence that in addition to the in-versus-out-group preferences, one's sociocultural-related stereotypical beliefs can account for racial disparities in pain-related decision-making.
Plasma anti-CD4 IgG levels are not associated with poor immune recovery in people with HIV initiating antiretroviral therapy
Authors: Bowler Scott A. , Premeaux Thomas A. , Ratzan Leo , Friday Courtney , Gianella Sara , Landay Alan L. , Ndhlovu Lishomwa C. ,   for the AIDS Clinical Trails Group NWCS 563
Published: December 2024

A segment of people with HIV on effective antiretroviral therapy (ART) continue to experience poor immune recovery, leaving them at heightened risk of non-AIDS-defining events (NAEs). The production of anti-CD4 IgG autoreactive antibodies is suggested as one contributing mechanism to these complications. Here, we found that plasma anti-CD4 levels do not discriminate immunological responders from nonresponders nor predict the occurrence of NAEs, suggesting it is unlikely a contributing immunopathological factor associated with these complications.
Adult Embryonal Rhabdomyosarcoma of the Prostate Presented on 18F-FDG and Al18F-FAPI-74 PET/CT
Authors: Cheng Xin , Hou Guozhu , Zheng Rong , Chen Xi , Wang Xuejuan
Published: December 2024

A 21-year-old man with a 2-week history of abdominal pain and urinary hesitancy was admitted to our hospital. Sarcoma was suspected based on his PSA level, age, and MRI findings. He underwent 18F-FDG and Al18F-FAPI-74 PET/CT scans. The scans revealed an irregularly dense prostate mass with indistinct borders to the rectum. The mass exhibited increased and heterogeneous FDG uptake and FAPI activity, with different distribution patterns between the 2 tracers. Histopathological analysis confirmed the diagnosis of embryonal rhabdomyosarcoma.
Central Nervous System Tumor-Embryonal Tumors Type With Neuroendocrine Differentiation
Authors: Edamadaka Yeshwanth , Parghane Rahul V , Basu Sandip
Published: December 2024

The central nervous system (CNS) tumor with embryonal tumors type is a rare type of CNS tumor with lack of unifying genetic alterations or diagnostic markers. The CNS tumor-embryonal tumors (CETs) have limited therapeutic options with high probability of adverse events associated with conventional treatment. Identification of somatostatin receptor expression and/or prostate-specific membrane antigen expression in CET patients by using PET/CT imaging may be helpful for deciding therapeutic approaches in these patients as theranostics. We present a 56-year-old woman who complained of headache, diminution of vision, and diagnosed CET and demonstrated high SSTR expression on PET/CT imaging, indicating peptide receptor radionuclide therapy could be effective therapeutic option in this case.
Superiority of 18F-FAPI-42 PET/CT in Eosinophilic Gastrointestinal Disorders
Authors: Dong Ye , Zhou Wenlan
Published: December 2024

We report a rare case of eosinophilic gastrointestinal disorders in a 60-year-old woman, which extensively involved the digestive tract from the esophagus, gastric, duodenum to the small intestine, depicted well by 18F-FAPI-42 PET/CT, superior to 18F-FDG PET/CT. Under the guidance of 18F-FAPI-42 PET/CT, the biopsy was successfully performed, and the diagnosis was established. This case highlights that 18F-FAPI-42 PET/CT may serve as a novel noninvasive method for evaluating eosinophilic gastrointestinal disorders.
Impact of Suture Materials on Surgical Site Infection in Oral Oncological Surgery With Free-Flap Reconstruction
Authors: Hidaka Takeaki , Miyamoto Shimpei , Furuse Kiichi , Fukunaga Yutaka , Oshima Azusa , Shinozaki Takeshi , Matsuura Kazuto , Wakabayashi Masashi , Higashino Takuya
Published: December 2024

Objective

The impact of suture materials on surgical site infections (SSIs) has been well documented in various surgical fields; however, it has not been thoroughly examined in oral oncological surgery with free-flap reconstruction. This study aimed to evaluate the incidence of oral SSIs associated with the use of monofilament and braided sutures for flap fixation.

Methods

A retrospective chart review of patients who underwent oral oncological resection with free-flap reconstruction was conducted between May 2020 and April 2024. Either monofilament (4-0 PDS® II or Monodiox®) or braided (3-0 Vicryl®) suture was used for flap suturing. The primary outcome was the incidence of oral SSIs, defined according to the guidelines of the United States Centers for Disease Control and Prevention. Multivariable logistic regression and inverse probability of treatment weighting based on propensity scores were used to estimate the risk differences.

Results

Of 209 eligible patients, 58 experienced oral SSIs, resulting in an incidence of 27.8%. Monofilament sutures were used in 174 patients and braided sutures in 35. The incidence of oral SSIs was higher in the braided suture group (42.9%) than in the monofilament suture group (24.7%). Analysis using propensity scores revealed a significantly higher risk of oral SSIs associated with braided sutures than with monofilament sutures, with a 18.5% risk difference (95% confidence interval, 2.1%–34.9%; P = 0.027).

Conclusions

Braided sutures may pose an increased risk of SSIs in oral oncological surgeries with free-flap reconstructions. Monofilament sutures are recommended for reconstructions, especially of the floor of the mouth.
Trends in Medicare Coverage of Overactive Bladder Medications in the United States
Authors: Gaddam Neha G. , Wallace Megan B. , Dieter Alexis A.
Published: December 2024

Importance

Strong evidence demonstrates long-term cognitive decline associated with anticholinergics. While prevalent among older populations, medical management of overactive bladder (OAB) is dictated by insurance coverage rather than medical provider and patient preferences.

Objective

The aim of this study was to assess Medicare insurance plan coverage for select OAB medications and evaluate coverage of preferred medications to medications with a greater risk of cognitive dysfunction.

Study Design

This cross-sectional study analyzed formularies and coverage tiers across 6 U.S. insurers for the following OAB medications: oxybutynin instant-release (IR) 5 mg, oxybutynin extended-release (ER) 5 mg, tolterodine IR 1 mg, tolterodine ER 2 mg, fesoterodine ER 4 mg, darifenacin 7.5 mg, solifenacin 5 mg, trospium IR 20 mg, trospium ER 60 mg, mirabegron 25 mg, and vibegron 75 mg. Coverage was compared between nonpreferred (oxybutynin, tolterodine, fesoterodine, darifenacin, solifenacin) and preferred medications (trospium, mirabegron, vibegron). Coverage scores, a weighted distribution based on coverage tier frequency relative to the number of plans investigated, were generated with a lower score indicating better coverage (range, 0.2–1.0).

Results

One thousand six hundred nineteen insurance plans representing an estimated 47% of the market share were evaluated. Oxybutynin IR had the best coverage score across insurers (0.4), whereas trospium ER had the worst (0.89). Preferred medications had worse coverage versus nonpreferred medications (P < 0.001). Centene had the best overall coverage and lowest initiation cost, whereas Aetna/CVS had the best coverage and initiation cost for preferred medications.

Conclusions

Beta-3 agonists had worse coverage across insurers nationwide. Current trends in Medicare coverage reveal a need for improved coverage of preferred OAB medications for an aging population already at risk of cognitive dysfunction.
Identification of a unique,de novo MYCBP2variant in an individual with highly superior autobiographical memory
Authors: Papassotiropoulos Andreas , Petrovska Jana , Arnold Andreas , LePort Aurora K.R. , Mastrandreas Pavlina , Neutzner Melanie , Freytag Virginie , Nesterenko Dmytro , Gharat Vaibhav , Schicktanz Nathalie , Vukojevic Vanja , Coynel David , Stetak Attila , Burri Noëlle , Ghaffari Navid , Riva Claudia , Durairaj Janani , Schwede Torsten , Bieri Oliver , Gräff Johannes , Skoulakis Efthimios M.C. , Henke Katharina , Cichon Sven , Taylor Verdon , Stark Craig E.L. , McGaugh James L. , Dean Camin , de Quervain Dominique J.-F.
Published: December 2024

Highly Superior Autobiographical Memory (HSAM) is an extremely rare condition characterized by an individual’s unparallelled ability to recall personal past events with exceptional detail and accuracy, including exact dates and days of the week, spanning many decades1–3. The molecular underpinnings of HSAM are unknown. Here, we investigated an individual with HSAM through neuropsychological testing, structural brain imaging, and genetic analyses. HSAM was confirmed as an isolated exceptional cognitive ability, with brain imaging revealing exceptionally large volumes of regions within the hippocampal formation, which have been previously linked to autobiographical memory. Using whole exome sequencing of the HSAM individual and their unaffected parents, we identified a uniquede novomissense variant inMYCBP2, which encodes an E3 ubiquitin-protein ligase4,5. To explore the potential behavioral consequences of this variant, we introduced the homologous variant intoC. elegans, which resulted in reduced forgetting and increased membrane-bound glutamate receptor in relevant neuronal cells. These findings show that the studied HSAM individual carries a unique,de novomissense variant inMYCBP2, which reduces forgetting in a model organism. The identification of functionally relevant genetic variants in individuals with superior memory traits has the potential to inform future research into memory-modulating therapies.
COVID-19 pandemic reshaped seasonal patterns and age distributions of respiratory viruses
Authors: He Miao , Gao Lanping , Hu Yanwu , Liang Simeng , Tang Jiajia , Zhao Yongliang , Zhang Youwei , Deng Na , Zhou Chanjuan , Wang Haoyue , Lan Xiyu , Wang Zixuan , Li Yanran , Xu Ke
Published: December 2024

Objectives

This study aims to investigate the changes in the prevalence and demographic characteristics of common respiratory viruses during and after the COVID-19 pandemic.

Methods

We retrospectively enrolled children with acute respiratory infections (ARIs) at Shiyan Renmin Hospital, Hubei University of Medicine, from January 2020 to December 2023. Specimens serum, nasopharyngeal aspirate, and alveolar lavage fluid were collected for direct immunofluorescence assay (DFA): respiratory syncytial virus (RSV), adenovirus (ADV), influenza A virus (IAV), influenza B virus (IBV), and parainfluenza virus (PIV). Demographic data and laboratory test results were analyzed accordingly.

Results

A total of 10,193 patients were enrolled. The positive infection rates for the years 2020, 2021, 2022, and 2023 were 3.97%, 3.15%, 36.20%, and 38.82%, respectively. The seasonal patterns for ADV transitioned from peaking in the summer and autumn of 2022 to summer and winter in 2023, while RSV peaked in the spring and summer of 2022 but moved to spring and autumn in 2023. PIV shifted from autumn 2022 to both spring and autumn in 2023. Intriguingly, IAV stably remained a two-season pattern of summer and winter in 2022 and 2023, while IBV showed up at 2022 winter but largely diminished later. The age distribution of children infected with ADV, RSV and PIV showed an upward trend, while no significant changes were observed for IAV and IBV.

Conclusions

The COVID-19 pandemic has disrupted the seasonal circulation of respiratory viruses. The seasonal pattern of influenza virus has been restored in 2022. In contrast, ADV, PIV, and RSV showed significant seasonal changes after the pandemic. The increasing age distributions of cases indicates an expanded age range of infection. Continuous monitoring of pathogen distribution and adjustment of preventive strategies are crucial for the effective management of pediatric ARIs.
Identifying differences between those with suicidal ideation-with-action, compared to ideation alone, using a community representative sample
Authors: Chan C , Wodchis W , Kurdyak P , Donnelly P
Published: December 2024

Background

Few studies examine suicidal ideation in the general population and who might act on suicidal thoughts. It is important to understand ideators, the largest group on the suicidality continuum.

Objectives

This study examines factors associated with suicidal ideation among community-dwelling individuals, and sociodemographic, health and help-seeking factors associated with ideation accompanied by planning or suicide attempt (‘ideation-with-action’) compared to ideation alone.

Methods

Using the 2002 and 2012 Canadian Community Health Surveys – Mental Health cycles (CCHS-MH), this cross-sectional cohort study examined 14,708 Ontarians 15 years and older who answered questions about suicidal ideation, and compared characteristics between non-ideators, ideators with a plan or previous attempt, and ideators alone, with chi-square tests and logistic regression.

Results

2.1% of CCHS respondents reported past-year ideation alone (n=302) and another 0.5% reported ideation with plan or past-year suicide attempt (n=76).

The risk profile of ideators compared to non-ideators was similar to that of ideators-with-action compared to ideators-without-action: male, younger, unpartnered, less educated, have lower income, no job, have a mood and anxiety disorder, a substance use disorder and seek help for mental health problems.

Most ideators (65%) do not seek help, and those with a plan or previous suicide attempt are more likely to do so.

Conclusion

Ideators differ in profile in terms of whether they have ideation only, have made a plan or had previous attempts. Risk factors differentiating ideators from non-ideators are the same factors that further differentiate ideators-with-action compared to those with only ideation, suggesting the existence of a suicidality continuum and opening up the opportunity for targeting common risk factors in prevention efforts.
Open-source cell culture automation system with integrated cell counting for passaging microplate cultures
Authors: Courville Greg , Vaid Shivanshi , Toruño Alexis , Lebel Paul , Cabrera Joana P. , Raghavan Preethi , Jacobsen Axel , Bell George , Leonetti Manuel D. , Gómez-Sjöberg Rafael
Published: December 2024

Tissue culture in 96-well microplates is conventionally a tedious, highly manual process subject to human error and sensitive to individual technique. Here, we describe the Automated Cell Culture Splitter (ACCS), a versatile and low-cost system for passaging plates of adherent or suspension cells, for routine culture maintenance or more specialized downstream applications such as seeding plates for microscopy. The system is built around the Opentrons OT-2 liquid handling robot and incorporates a novel on-deck imaging-based cell counting instrument which allows it to compensate for density disparities across a source plate and control the number of cells seeded on a per-well basis. We find this solution compares favorably to our existing manual cell culture processes in terms of both accuracy and biological out-comes while cutting the hands-on time required per plate by more than half. The system is designed to be readily adaptable, and we anticipate that it could find uses in a variety of scenarios as an accessible entry point into automation for high-throughput cell culture; to that end, all of the source code and hardware designs are released under open source licenses.
Muller’s ratchet and gene duplication
Authors: Freund Fabian , Wirtz Johannes , Zheng Yichen , Schäfer Yannick , Wiehe Thomas
Published: December 2024

Copy number of genes in gene families can be highly variable among individuals and may continue to change across generations. Here, we study a model of duplication-selection interaction, which is related to Haigh’s mutation-selection model of Muller’s ratchet. New gene copies are generated by duplication but fitness of individuals decreases as copy number increases. Our model comes in two flavours: duplicates are copied either from a single template or from any existing copy. A duplication-selection equilibrium exists in both cases for infinite size populations and is given by a shifted Poisson or a negative binomial distribution. Unless counteracted by synergistic epistasis, finite populations suffer from loss of low copy-number haplotypes by drift, forcing them into a regime called ‘run-away evolution’ in which new copies accumulate without bound nor equilibrium. We discuss a few empirical examples and interpret them in the light of our models. Generally, large gene families appear too over-dispersed to fit the single template model suggesting a dynamic, and potentially accelerating, duplication process.
Rapid identification of African swine fever virus in diagnostic samples using CRISPR-Cas
Authors: Kambakam Sekhar , Thomas Julia , Robbe-Austerman Suelee , Shanmuganatham Karthik , Palinski Rachel
Published: December 2024

African Swine Fever Virus (ASFV) is a high consequence, highly transmissible pathogen affecting swine causing African Swine Fever (ASF), a devastating disease, with high mortality rates in naive populations. Due to the likelihood of significant economic impacts associated with an ASF outbreak, considerable resources have been allocated in the United States (U.S.) to safeguard the swine industry against this threat. Ongoing outbreaks of ASF in the Dominican Republic and Haiti further threaten U.S. swine due to their proximity and involvement in movement to and from North America. While surveillance programs are ongoing, there are limited point-of-care (POC) tests available during outbreaks that maintain the sensitivity and specificity standards of laboratory testing (e.g., qPCR). However, the recently developed CRISPR-Cas testing systems may provide comparable high-quality results. In a CRISPR-based diagnostic assay, CRISPR effectors can be programmed with CRISPR-RNA (crRNA) to target specific DNA or RNA. Upon target binding, the Cas enzyme undergoes collateral cleavage of nearby fluorescently quenched reporter molecules (ssDNA or ssRNA), which can be detected under blue light or a fluorescence microplate reader. Furthermore, this tool is rapid, simple, cost-effective and can be performed with inexpensive equipment. For these reasons, we sought to develop a low-cost visual detection method for ASFV by employing the recombinase polymerase amplification (RPA)-dependent CRISPR-Cas12a technique that can be utilized in the field as a point-of-care-assay. Our CRISPR-Cas12a assay demonstrated comparable sensitivity and specificity to qPCR, both visually and when quantified using a fluorescent reader. In whole blood samples from ASFV-suspect or ASFV-negative cases, the CRISPR assay achieved a sensitivity of 98.3% (102 DNA copies) and a specificity of 100%. Finally, an assessment of the reaction time constraints indicated that results can be visualized in as little as seven minutes with a peak fluorescence at 40 min (RPA and CRISPR steps). The results of this feasibility assay validation allow for the rapid development of sensitive and specific POC tests that may be used for outbreak response in the future.