bluuebunny/crossref_metadata_2025 huggingface dataset:
RERconverge Expansion: Using Relative Evolutionary Rates to Study Complex Categorical Trait Evolution
Authors: Redlich Ruby , Kowalczyk Amanda , Tene Michael , Sestili Heather H , Foley Kathleen , Saputra Elysia , Clark Nathan , Chikina Maria , Meyer Wynn K , Pfenning Andreas R
Published: October 2024

Comparative genomics approaches seek to associate molecular evolution with the evolution of phenotypes across a phylogeny. Many of these methods lack the ability to analyze non-ordinal categorical traits with more than two categories. To address this limitation, we introduce an expansion to RERconverge that associates shifts in evolutionary rates with the convergent evolution of categorical traits. The categorical RERconverge expansion includes methods for performing categorical ancestral state reconstruction, statistical tests for associating relative evolutionary rates with categorical variables, and a new method for performing phylogeny-aware permutations, “permulations”, on categorical traits. We demonstrate our new method on a three-category diet phenotype, and we compare its performance to binary RERconverge analyses and two existing methods for comparative genomic analyses of categorical traits: phylogenetic simulations and a phylogenetic signal based method. We present an analysis of how the categorical permulations scale with the number of species and the number of categories included in the analysis. Our results show that our new categorical method outperforms phylogenetic simulations at identifying genes and enriched pathways significantly associated with the diet phenotypes and that the categorical ancestral state reconstruction drives an improvement in our ability to capture diet-related enriched pathways compared to binary RERconverge when implemented without user input on phenotype evolution. The categorical expansion to RERconverge will provide a strong foundation for applying the comparative method to categorical traits on larger data sets with more species and more complex trait evolution than have previously been analyzed.
The three YTHDF paralogs and VIRMA are strong cross-histotype tumor driver candidates among m6A core genes
Authors: Destefanis Eliana , Sighel Denise , Dalfovo Davide , Gilmozzi Riccardo , Broso Francesca , Cappannini Andrea , Bujnicki Janusz M , Romanel Alessandro , Dassi Erik , Quattrone Alessandro
Published: October 2024

N6-Methyladenosine (m6A) is the most abundant internal modification in mRNAs. Despite accumulating evidence for the profound impact of m6A on cancer biology, there are conflicting reports that alterations in genes encoding the m6A machinery proteins can either promote or suppress cancer, even in the same tumor type. Using data from The Cancer Genome Atlas, we performed a pan-cancer investigation of 15 m6A core factors in nearly 10000 samples from 31 tumor types to reveal underlying cross-tumor patterns. Altered expression, largely driven by copy number variations at the chromosome arm level, results in the most common mode of dysregulation of these factors. YTHDF1, YTHDF2, YTHDF3 and VIRMA are the most frequently altered factors and the only ones to be uniquely altered when tumors are grouped according to the expression pattern of the m6A factors. These genes are also the only ones with coherent, pan-cancer predictive power for progression-free survival. On the contrary, METTL3, the most intensively studied m6A factor as a cancer target, shows much lower levels of alteration and no predictive power for patient survival. Therefore, we propose the non-enzymatic YTHDF and VIRMA genes as preferred subjects to dissect the role of m6A in cancer and as priority cancer targets.
Ideal Time to Conduct a Pharmacokinetic Investigation After Delivery to Fully Capture the Effect of Pregnancy on Drug Exposure
Authors: Berton Mattia , Stader Felix , Bettonte Sara , Battegay Manuel , Marzolini Catia
Published: October 2024

Background

The World Health Organization is pushing to accelerate the study of new human immunodeficiency virus drugs in pregnant women. However, regulatory guidelines do not specify when to conduct pharmacokinetic studies in postpartum women. This knowledge gap carries the potential to jeopardize the outcomes and conclusions of clinical trials aiming to study the effect of pregnancy on drug exposure. We used physiologically based pharmacokinetic (PBPK) modeling along with clinical data to determine the time needed after delivery for drug exposure to return to prepregnancy levels.

Methods

A literature review was conducted to collect physiological parameters of pregnant and postpartum women. Regression analyses were performed to derive equations describing the parameters trajectory throughout pregnancy and post partum to inform our PBPK model. Published pharmacokinetic data in pregnant and postpartum women were used for the model verification. The PBPK model was subsequently applied to investigate pharmacokinetic changes throughout pregnancy and post partum.

Results

In agreement with the clinical data the PBPK model was able to describe the different effects of pregnancy on drug exposure, with bictegravir showing the largest reduction in exposure (approximately 50%) during the third trimester while ritonavir and raltegravir showing the lowest (approximately 30%). The successfully verified PBPK model predicted that all evaluated antiretrovirals mostly return to prepregnancy exposure 4 weeks after delivery.

Conclusions

Pharmacokinetic investigations on hepatically cleared drugs should not be conducted before the fifth week after delivery to fully characterize the effect of pregnancy on drug exposure. Because physiological changes remain after delivery, early measurements can underestimate the pregnancy effect on pharmacokinetics, leading to suboptimal dosing recommendations during pregnancy.
Feathers, folklore, and eco-literacy: Stories ascribe cultural keystone status to avian scavengers in South Asian cities
Authors: Gupta Urvi , Kumar Nishant
Published: October 2024

We examined the cultural significance of commensal avian scavenger species—vultures, kites, and crows—and their exploitation of anthropogenic resources and sentiments within Delhi’s urban landscapes. For this, we investigated the intrinsic values attributed to these birds by people, which are indicative of complex, rapidly urbanizing social-ecological systems. Semi-structured interviews revealed folk perceptions intertwined with socio-cultural narratives and traditions, shaped by observations of avian morphology, ecology, and behavior. Birds’ nesting habits, habitats, home ranges, and foraging behaviors affected people’s perceptions, while ecosystem services inspired zoomorphism and anthropomorphism via vernacular-nomenclature (e.g., chidiya collectively for songbirds, giddha for scavenging raptors). Culturally rooted perceptions, which informed ritual feeding practices and shaped prevalent attitudes toward commensal species, fostered mutual tolerance, and brought people into closer contact with urban biodiversity. Such physical and cultural proximity is a defining characteristic distinguishing tropical urban ecosystems from their Western counterparts. We also uncovered the web of social-technological influences on animal-related folk stories. The urbanization of perceptions in vulture extinction zones revealed shifts in social–ecological relationships with wildlife. It adds cultural dimensions to the currently appreciated keystone status of vultures, vital for their erstwhile coexistence at extremely high densities in South Asia. Urban transformations, technological advancements, and media exposure potentially reshaped human–animal interface, with media misinformation affecting personalized ecologies. Conflicts and health concerns arose from media narratives on garbage-consuming animals. Our findings offer insights to prevent severing of people and nature connections due to urbanization (e.g., technological applications can integrate scientific knowledge with biocultural narratives and folklore), promoting a new-age eco-literacy.
AUXIN RESPONSE FACTOR 2 mediates repression of strawberry receptacle ripening via auxin-ABA interplay
Authors: Li Bai-Jun , Shi Yan-Na , Xiao Yan-Ning , Jia Hao-Ran , Yang Xiao-Fang , Dai Zheng-Rong , Sun Yun-Fan , Shou Jia-Han , Jiang Gui-Hua , Grierson Donald , Chen Kun-Song
Published: October 2024

Cultivated strawberry (Fragaria × ananassa) is a popular, economically important fruit. The ripening of the receptacle (pseudocarp), the main edible part, depends on endogenously produced abscisic acid (ABA) and is suppressed by the high level of auxin produced from achenes (true fruit) during early development. However, the mechanism whereby auxin regulates receptacle ripening through inhibiting ABA biosynthesis remains unclear. Here, we identified AUXIN RESPONSE FACTOR 2 (FaARF2), which showed decreased expression with reduced auxin content in the receptacle, leading to increased ABA levels and accelerated ripening. Dual-luciferase, yeast one-hybrid, and electrophoretic mobility shift assays demonstrated that FaARF2 could bind to the AuxRE element in the promoter of 9-CIS-EPOXYCAROT-ENOID DIOXYGENASE 1 (FaNCED1), a key ABA biosynthetic gene, to suppress its transcriptional activity. Transiently overexpressing FaARF2 in the receptacles decreased FaNCED1 expression and ABA levels, resulting in inhibition of receptacle ripening and of development of quality attributes, such as pigmentation, aroma, and sweetness. This inhibition caused by overexpressing FaARF2 was partially recovered by the injection of exogenous ABA; conversely, transient silencing of FaARF2 using RNA interference produced the opposite results. The negative targeting of FaNCED1 by FaARF2 is a key link between auxin-ABA interactions and regulation of strawberry ripening.
Noninvasive brain stimulation beyond the motor cortex: a systematic review and meta-analysis exploring effects on quantitative sensory testing in clinical pain
Authors: Flood Andrew , Cavaleri Rocco , Chang We-Ju , Kutch Jason , Toufexis Constantino , Summers Simon J
Published: October 2024

Background

Noninvasive brain stimulation (NIBS) has been investigated increasingly as a means of treating pain. The effectiveness of NIBS in the treatment of pain has traditionally focused on protocols targeting the primary motor cortex (M1). However, over time, the effectiveness of M1 NIBS has been attributed to effects on interconnected cortical and subcortical sites rather than on M1 itself. Although previous reviews have demonstrated the effectiveness of non-M1 NIBS in improving subjective reports of pain intensity, the neurophysiological mechanisms underlying these effects remain incompletely understood. As chronic pain is associated with pain hypersensitivity and impaired endogenous descending pain modulation, it is plausible that non-M1 NIBS promotes analgesic effects by influencing these processes.

Objective

The aim of this systematic review and meta-analysis was therefore to evaluate the effect of NIBS over non-M1 sites on quantitative sensory testing measures in clinical pain populations.

Methods

A systematic search of electronic databases was conducted from inception to January 2024. Included articles (13 trials, n = 565 participants) were appraised with the Physiotherapy Evidence Database (PEDro) scale and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE), and a random-effects model was used to meta-analyze outcomes where possible.

Results

A small number of studies found that NIBS applied to the dorsolateral prefrontal cortex might improve pain modulation in patients with fibromyalgia and that stimulation of the posterior superior insula and prefrontal cortex could improve pain sensitivity in chronic neuropathic and osteoarthritic pain, respectively. However, findings varied among studies, and there remains a paucity of primary research.

Conclusion

This review indicates that current literature does not provide clear evidence that NIBS over non-M1 sites influences pain processing.

Study registration

PROSPERO (CRD42020201076)
Descriptive norms can “backfire” in hyper-polarized contexts
Authors: Rand David G , Yoeli Erez
Published: October 2024

Descriptive social norms interventions, where a behavior is promoted by learning that others engage in that behavior, are a cornerstone of behavior change research and practice. Here, we examine the effect of learning about the behavior of outgroup members in a hyper-polarized context: mask-wearing during the COVID-19 pandemic. Contrary to prior findings, we find a descriptive social norm “backfire”: Across three experiments, Biden supporters increased their mask-wearing intentions after being informed that most Trump supporters never wore masks. We also provide evidence consistent with a mechanism whereby this effect was driven by changes in perceptions about how negatively ingroup members view nonmask wearing. Finally, in a fourth study, Biden supporters show the traditional descriptive norms effect (rather than a backfire) from the same treatment when in a nonpolarized context: dishonesty in a coin-flipping task. These findings help to clarify why descriptive social norm interventions promote behavior change, and underscore the importance of social norms in motivating prosocial behaviors. They also suggest an update to current best practices in the design of descriptive norm interventions: in polarized contexts, it can be beneficial to publicize antisocial behavior of outgroup members.
Testing the social pressure hypothesis: Does in-party social pressure reduce out-party empathy?
Authors: Pradella Lea
Published: October 2024

Empathy is considered one of the most critical components for bridging political divides and reducing animosity between political groups. Yet, empathy between political opponents is rare. There is a growing concern that partisans do not empathize with out-partisans because they feel social pressure from fellow in-partisans not to do so. This article examines this social pressure hypothesis and draws two conclusions. First, on the surface, the hypothesis seems plausible: citizens perceive fellow in-partisans as comparatively disapproving of and reluctant to engage in out-party empathy, and naïve cross-sectional analyses suggest that this perception translates into lower empathy towards out-partisans. Second, however, experimental data suggest that this relationship is not causal. Expecting disapproval from fellow in-party members for empathizing with out-partisans does not lead to a significant reduction in intentions to empathize with out-partisans. Rather, exploratory analyses suggest that social pressure by the in-party increases empathy toward out-partisans and triggers disappointment toward in-partisans. This implies that partisans can resist social pressure from the in-party and might even compensate for in-partisans’ lack of out-party empathy. The results are supported by original cross-sectional and experimental survey data (N=2,535) collected in the United States, an arguably most likely case for in-party social pressure to shape partisans’ intentions. The results have important implications for understanding the causes of and viable strategies for building empathy across political divides.
CODI: Enhancing machine learning-based molecular profiling through contextual out-of-distribution integration
Authors: Eissa Tarek , Huber Marinus , Obermayer-Pietsch Barbara , Linkohr Birgit , Peters Annette , Fleischmann Frank , Žigman Mihaela
Published: October 2024

Molecular analytics increasingly utilize machine learning (ML) for predictive modeling based on data acquired through molecular profiling technologies. However, developing robust models that accurately capture physiological phenotypes is challenged by the dynamics inherent to biological systems, variability stemming from analytical procedures, and the resource-intensive nature of obtaining sufficiently representative datasets. Here, we propose and evaluate a new method: Contextual Out-of-Distribution Integration (CODI). Based on experimental observations, CODI generates synthetic data that integrate unrepresented sources of variation encountered in real-world applications into a given molecular fingerprint dataset. By augmenting a dataset with out-of-distribution variance, CODI enables an ML model to better generalize to samples beyond the seed training data, reducing the need for extensive experimental data collection. Using three independent longitudinal clinical studies and a case–control study, we demonstrate CODI’s application to several classification tasks involving vibrational spectroscopy of human blood. We showcase our approach’s ability to enable personalized fingerprinting for multiyear longitudinal molecular monitoring and enhance the robustness of trained ML models for improved disease detection. Our comparative analyses reveal that incorporating CODI into the classification workflow consistently leads to increased robustness against data variability and improved predictive accuracy.
Standard Errors for Calibrated Parameters
Authors: Cocci Matthew D , Plagborg-Møller Mikkel
Published: October 2024

Calibration, the practice of choosing the parameters of a structural model to match certain empirical moments, can be viewed as minimum distance estimation. Existing standard error formulas for such estimators require a consistent estimate of the correlation structure of the empirical moments, which is often unavailable in practice. Instead, the variances of the individual empirical moments are usually readily estimable. Using only these variances, we derive conservative standard errors and confidence intervals for the structural parameters that are valid even under the worst-case correlation structure. In the over-identified case, we show that the moment weighting scheme that minimizes the worst-case estimator variance amounts to a moment selection problem with a simple solution. Finally, we develop tests of over-identifying or parameter restrictions. We apply our methods empirically to a model of menu cost pricing for multi-product firms and to a heterogeneous agent New Keynesian model.
Soluble urine activated leukocyte cell adhesion molecule is a strong predictor of lupus nephritis
Authors: Chu Dalena , Schwartz Noa , Ampudia Jeanette , Guthridge Joel , James Judith , Buyon Jill P , Connelly Stephen , Fung Maple , Ng Cherie T ,   The Accelerating Medicines Partnership: RA/SLE Network, Anolik Jennifer , Apruzzese William , Arazi Arnon , Berthier Celine , Brenner Michael , Buyon Jill , Clancy Robert , Connery Sean , Cunningham Melissa , Dall’Era Maria , Davidson Anne , Der Evan , Fava Andrea , Fonseka Chamith , Furie Richard , Goldman Dan , Gupta Rohit , Guthridge Joel , Hacohen Nir , Hildeman David , Hoover Paul , Hsu Raymond , James Judith , Kado Ruba , Kalunian Ken , Kamen Diane , Kretzler Mattias , Maecker Holden , Massarotti Elena , McCune William , McMahon Maureen , Park Meyeon , Payan-Schober Fernanda , Pendergraft William , Petri Michelle , Pichavant Mina , Putterman Chaim , Rao Deepak , Raychaudhuri Soumya , Slowikowski Kamil , Suryawanshi Hemant , Tuschl Thomas , Utz P J , Waguespack Dia , Wofsy David , Zhang Fan , Fava Andrea , Petri Michelle , Mohan Chandra , Putterman Chaim
Published: October 2024

Objectives

To evaluate urinary activated leucocyte cell adhesion molecule (ALCAM) and CD6 as predictors of LN progression or disease resolution across a 1-year study.

Methods

Serum and urine samples from biopsy proven LN subjects (n = 122) were prospectively collected over the course of a year at 3- or 6-month intervals (weeks 0, 12, 26 and 52) across multiple study sites and assessed for soluble ALCAM and CD6 levels. Urine creatinine from the same urine sample was used to normalize the levels of urinary ALCAM and urinary CD6. Measured levels of serum and urine ALCAM and CD6 were then analysed against disease metrics cross-sectionally and longitudinally.

Results

Cross-sectional analysis at baseline revealed that urinary ALCAM significantly correlated with urine protein creatinine ratio, renal SLEDAI, and the Physician Global Assessment (PGA), and negatively correlated with serum C3 and C4. Receiver operating characteristic curve analysis demonstrated that urinary ALCAM is a predictor of LN with an area under the curve (AUC) of 0.97, compared with urinary CD6 with an AUC of 0.71. Importantly, the change in urinary ALCAM over a 3-month period distinguished between non-responders and responders at week 52.

Conclusion

Urinary ALCAM is reflective of changes in LN and may be predictive of response status.
Neither increasing the frequency of sow feedings nor decreasing the interval between feedings prior to farrowing reduced piglet stillbirths
Authors: Johnson Danielle C , Perez Jeremy G , Estrada Jorge , Corzatt Deanne , Welch Michael W , Parr Eric , Boler Dustin D
Published: October 2024

Farrowing durations that exceed 240 min cause stillborn rates to increase. Therefore, feeding strategies in late gestation have been studied to mitigate the negative consequences of extended farrowing durations. A total of 1,501 sows (PIC 1050 Camborough) were used for this study at two individual farms near Carthage, IL. Farm 1 (758 sows) was a porcine reproductive and respiratory virus (PRRSv) stable (previously experienced a PRRSv outbreak and is currently vaccinated for PRRSv) with an older parity structure (3.67). Farm 2 (743 sows) was PRRSv positive (sows with pigs demonstrating Ct values <36 determined by pig processing fluids) and had a younger parity structure (2.96). Sows were moved into farrowing rooms at approximately day 112 of gestation and started on their respective treatment. Treatment 1 sows were fed 1 meal of 2.27 kg per day at 0600 h. Treatment 2 sows were fed two equal meals of 1.13 kg (2.27 kg total) at 0600 and 1400 h. Treatment 3 sows were fed two equal meals of 1.13 kg (2.27 kg total) at 0600 and 1800 h. Treatment 4 sows were fed three equal meals of 0.77 kg (2.27 kg total) at 0600, 1400, and 2200 h. Treatments were assigned to farrowing rooms in a replicated 4 × 4 Latin Square arrangement of treatments where each treatment was fed in each room one time at each farm. Daily feed intakes were recorded from the time sows were introduced to the farrowing room until 5 d after farrowing. The total number of pigs born, pigs born alive, stillbirths, and mummies were recorded for each litter within 24 h of farrowing. Live pigs were weighed as a group to record litter birth weight. Pig mortality and morbidities were recorded until 5 d after farrowing. The total number of pigs born and pigs born alive were not different (P ≥ 0.59) among treatments. The number of stillborn pigs was not different (P = 0.33) among treatment 1(1.15 ± 1.41), treatment 2 (1.20 ± 1.36), treatment 3 (1.30 ± 1.46), and treatment 4 (1.14 ± 1.28). Sows fed three times per day at 8 h intervals tended (P = 0.08) to reduce the percentage of sows farrowed under supervision compared with sows fed once a day. Sows fed twice per day at 12 h intervals reduced (P = 0.01) the percentage of sows provided assistance compared with feeding sows once per day. Feeding a sow one meal of 2.27 kg, two meals (2.27 kg total), or three meals (2.27 kg total) of feed a day before farrowing did not reduce the number of stillborn piglets regardless of farm health status or parity structure.
Liquid chromatography–high-resolution mass spectrometry-based metabolomics revealing the effects of zearalenone and alpha-zearalenol on human endometrial cancer cells
Authors: Marhaba Marhaba , Nagendla Narendra Kumar , Anjum Saria , Ganneru Sireesha , Singh Varsha , Pal Saurabh , Mudiam Mohana Krishna Reddy , Ansari Kausar Mahmood
Published: October 2024

Human exposure to mycotoxins through food involve a mixture of compounds, which can be harmful to human health. The Fusarium fungal species are known to produce zearalenone (ZEN), a non-steroidal estrogenic mycotoxin, and its metabolite alpha-zearalenol (α-ZEL), both of which possess endocrine-disruptive properties. Given their potential harm to human health through food exposure, investigating the combined effects of ZEN and α-ZEL becomes crucial. Hence, the combined impact of ZEN and α-ZEL study hold significant importance. This in vitro study delves into the critical area, examining their combined impact on the proliferation and metabolic profile of endometrial cancer Ishikawa cells via sulforhodamine, clonogenic, proliferating cell nuclear antigen (PCNA) and liquid chromatography-high resolution mass spectrometry (LC-HRMS) based untargeted metabolomics. Low concentrations of ZEN (25 nm), α-ZEL (10 nm), or a combination of both were observed to significantly enhance cell proliferation of Ishikawa cells, as evidenced by PCNA immunostaining, immunoblotting as well and clonogenic assays. The metabolomics revealed the perturbations in glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and phenylalanine, tyrosine, tryptophan biosynthesis provides valuable insights into potential mechanism by which these mycotoxins may facilitate cell proliferation. However, further investigations are warranted to comprehensively understand the implications of these findings and their possible implications for human health.
4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) exposure induces hepatotoxicity and nephrotoxicity – role of oxidative stress, mitochondrial dysfunction and pathways of cytotoxicity
Authors: Maadurshni Gobichettipalayam Balasubramaniam , Nagarajan Manikandan , Mahalakshmi Balamurali , Sivasubramanian Jeganathan , Hemamalini Vedagiri , Manivannan Jeganathan
Published: October 2024

Objective

Bisphenol A (BPA) is a ubiquitous pollutant worldwide and 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is considered a major active metabolite of BPA with a wide range of potent toxicological properties. However, its adverse outcome pathway (AOP) on the hepatic and renal system has not yet been explored.

Methods

Hence, the current study evaluated its effect on cell survival, oxidative stress, and apoptosis. In addition, the influence of signalling pathways on cytotoxicity and ROS generating enzymes (NOX2 and XO) on oxidative stress was explored by siRNA knockdown experiments. Further, its molecular interaction with SOD, CAT, and HSA (molecular docking and dynamics) was evaluated and validated with spectroscopy (fluorescence and FTIR) based methods.

Results

The outcome indicates that MBP exposure dose dependently increased the cytotoxic response, oxidative stress, and apoptosis in both hepatocytes and kidney cells. Further, MAPK signalling pathways and oxidative stress influenced the overall cytotoxic response in both cells. In addition, the stimulatory (NOX2 and XO) and inhibitory (SOD and CAT) effects of MBP were observed, along with a robust interaction with HSA.

Conclusions

The overall observation illustrates that MBP exposure adversely impacts hepatic and renal cells through oxidative stress and relevant molecular pathways which may connect the missing links during risk assessment of BPA.
Liver toxicity and repair evaluated by histopathology and electric modulus
Authors: Elwan Azhar M , Farag Ibrahim M , Elnasharty Mohamed M M
Published: October 2024

Detoxification is one of the most important liver functions. Therefore, liver is the front line of defense when the biosystem faces drug overdose, toxins, and anything that may cause harm. Some famous antibiotics are known for their side effects on liver; one of them is amoxicillin, AM. This work has investigated the toxic effect of amoxicillin on rat’s liver with overdose (90 mg/kg) and has studied the ameliorative role of protective and therapeutic Ashwagandha seeds extract (ASE) at doses (100, 200, and 300 mg/kg) against this toxicity. To achieve this work, the authors used two modalities; the first is liver histopathology to figure out the amoxicillin and ASE effects and to detect the sensitivity of another modality; the electric modulus, and its related thermodynamic parameters of liver tissue. Histopathological examination showed that the role of therapeutic ASE in reducing amoxicillin (AM) toxicity was more effective than the protective one. Also, most dielectric and thermodynamic results achieved the same result. Histopathology confirmed the liver injury by amoxicillin and the partial repair by the biosystem using ASE. Moreover, electric modulus, related dielectric parameters, and their thermodynamic state functions showed different changes in their values under the effect of amoxicillin. Using ASE helped the biosystem to restore these changes near their control values.
On the importance of assessing topological convergence in Bayesian phylogenetic inference
Authors: Brusselmans Marius , Carvalho Luiz Max , L. Hong Samuel , Gao Jiansi , Matsen IV Frederick A , Rambaut Andrew , Lemey Philippe , Suchard Marc A , Dudas Gytis , Baele Guy
Published: October 2024

Modern phylogenetics research is often performed within a Bayesian framework, using sampling algorithms such as Markov chain Monte Carlo (MCMC) to approximate the posterior distribution. These algorithms require careful evaluation of the quality of the generated samples. Within the field of phylogenetics, one frequently adopted diagnostic approach is to evaluate the effective sample size and to investigate trace graphs of the sampled parameters. A major limitation of these approaches is that they are developed for continuous parameters and therefore incompatible with a crucial parameter in these inferences: the tree topology. Several recent advancements have aimed at extending these diagnostics to topological space. In this reflection paper, we present two case studies—one on Ebola virus and one on HIV—illustrating how these topological diagnostics can contain information not found in standard diagnostics, and how decisions regarding which of these diagnostics to compute can impact inferences regarding MCMC convergence and mixing. Our results show the importance of running multiple replicate analyses and of carefully assessing topological convergence using the output of these replicate analyses. To this end, we illustrate different ways of assessing and visualizing the topological convergence of these replicates. Given the major importance of detecting convergence and mixing issues in Bayesian phylogenetic analyses, the lack of a unified approach to this problem warrants further action, especially now that additional tools are becoming available to researchers.
A Neglected Fracture: Treatment and Infection of Seymour Fractures of the Hallux in the Pediatric Population
Authors: Batley Morgan G. , Krakow Arielle , Pascual-Leone Nicolas , Lee Sydney , Hall Carter E. , Sarkar Sulagna , Talwar Divya , Davidson Richard S.
Published: October 2024

Introduction:

Seymour physeal fractures of the distal phalanx of the Hallux in children are common but rarely described in the literature. There is limited literature investigating how these fractures should be specifically treated. Generally, good results are reported when open fractures are treated with debridement and antibiotics. This large retrospective review evaluates incidence of infection and compares outcomes of various treatments for Seymour physeal fractures of the distal phalanx of the Hallux in children.

Methods:

This study included patients ≤18 years of age treated for Seymour fractures of the Hallux between January 1, 2007, and November 20, 2018, at a single tertiary-care urban children’s hospital. Demographic, injury, and treatment data were obtained via a retrospective review of electronic medical records, including closed versus open fracture status, time to treatment, and whether antibiotics were prescribed and taken. Initial radiographic imaging was examined by a single attending surgeon for angulation (degrees) and widening (mm). Outcome variables included the development of infection and the rate and success of healing.

Results:

One hundred thirty-eight patients were included in our analysis. Most (84/138, 61%) fractures were closed and treated successfully without antibiotics. Treatment for open fractures varied greatly, with many of these fractures undergoing an incision and drainage procedure (I&D) (33/54, 61%) and antibiotic prescription (43/54, 76%). Most (47/54, 87%) open fractures did not develop infection. However, 7/54 open fractures presented with an active infection. Four out of seven (29%) of these fractures did not receive any treatment before infection presentation. Two others who presented with infection both had delayed antibiotics and neither underwent I&D. Fractures that either presented with or developed an infection presented significantly later than those fractures that did not develop infection (P<0.001). Neither angulation nor displacement correlated to the time of healing or development of infection.

Conclusions:

In our large cohort, the majority of open Seymour fractures of the Hallux treated in a timely manner did not develop infection, regardless of treatment. However, open fractures that presented multiple days after injury had an increased incidence of infection. Thus, for open fractures, we recommend timely antibiotics and I&D. Closed fractures may be treated conservatively, with no indication for reduction or use of antibiotics.
Radial Longitudinal Deficiency: Description of a Novel Surgical Technique and Clinical Cases
Authors: Vergara-Amador Enrique , López-Rincón Laura , Romero Barreto Camilo , Almario-Aristizábal Tatiana
Published: October 2024

Radial longitudinal deficiency III and IV present as a short upper limb, functional elbow, and wrist with severe radial and palmar angulation, where the carpus articulates with the radial and palmar edge of the ulna, allowing limited mobility in a nonfunctional position. Surgical treatment aims to correct radial angulation and flexed carpal position, often altering carpal positioning over the distal ulna and impacting wrist mobility. In addition, fixation through distal ulnar epiphysis affects its growth. Although these procedures improve appearance, functionality remains suboptimal. This study describes a novel ulnar osteotomy and extensor carpi ulnaris transfer for the correction of wrist deformity in radial longitudinal deficiency with preservation of ulnocarpal motion and epiphyseal growth. The surgical technique, indications, contraindications, and potential complications are described. Three cases with postoperative follow-ups at 36, 12, and 6 months, evaluating deformity and pre/postsurgical wrist mobility ranges, are reported. A correction was achieved in the forearm-hand angle of 71 to 88 degrees of the initial. The total range of movement, between 50 degrees and 80 degrees, was almost the same before and after the operation in the most anatomic position. In one patient, there was a residual deformity at the dorsoradial border, which showed no progression during the last 6 months of follow-up. For patients with radial longitudinal deficiency, functional outcomes with preserved mobility appear to hold greater significance. The technique described in this study enabled deformity correction while maintaining a wide range of motion. The preservation of the physis in a different orientation is an aspect that will need evaluation in long-term follow-up but offers potential treatment options in the future; due to the unknown of the secondary deformity, it is recommended that the long-term results should be awaited before adoption of this technique.
Drug Interaction of SGLT2Is and ARNI on Acute Kidney Injury: A Real-World Pharmacovigilance Analysis Through the FAERS
Authors: Zhao Subei , He Ronghua , Mei Mei , Yu Meng , Yang Zheng , Tian Chunyan , Zhang Ping , Li Rong
Published: October 2024

Sodium–glucose cotransporter 2 inhibitors (SGLT2Is) and angiotensin receptor–neprilysin inhibitor (ARNI) may cause potential renal damage, the combined impact of SGLT2Is and ARNI on acute kidney injury (AKI) remains unclear. This pharmacovigilance study conducted a disproportionality analysis using reports from the FDA Adverse Event Reporting System database. The reporting odds ratio was used as an estimate for detecting AKI signal. A total of 659,573 reports on at least 1 glucose-lowering drug and/or ARNI were obtained. Of the 413 reports on cotherapy of SGLT2Is and ARNI, 99 (24.0%) reports mentioned AKI. Overall, the AKI reporting rate significantly increased in cotherapy (adjusted reporting odds ratio, 95% confidence interval: 8.04, 6.20–10.42, P < 0.001), with a stronger AKI signal in cotherapy of canagliflozin and ARNI (16.82, 3.75–75.57, P < 0.001). Specifically, no increased AKI signal was detected in patients with heart failure (HF) receiving cotherapy after adjustment for sex and age (HF: 1.27, 0.89–1.80, P = 0.189; HF plus diabetes: 2.08, 0.99–4.40, P = 0.055; or HF plus hypertension: 1.69, 0.53–5.35, P = 0.376), whereas enhanced AKI signals were detected in patients with diabetes (20.57, 11.93–35.46, P < 0.001), hypertension (4.30, 1.98–9.37, P < 0.001), or diabetes plus hypertension (5.44, 1.92–15.43, P = 0.001). This study reveals that superimposed renal impairment results from cotherapy with SGLT2Is and ARNI. It is necessary to be vigilant that the elderly patients with diabetes, hypertension, or chronic kidney disease are more susceptible to AKI, especially if they likewise receive diuretics. When cotherapy is unavoidable, early monitoring of renal function, blood volume, and blood pressure is excessively crucial. However, it is relatively safe in patients with HF.
When Giant Lymphangioma Meets Hydrops Fetalis: An Uncommon Case Report of Lower Extremity Involvement
Authors: Martin Ariana Marie , Sanchez-Cantu Andrea Paola , Cantu-Rodriguez Andrea , Martinez-Salinas Raul , Valdez-Bocanegra Jesus Damian
Published: October 2024

Approximately 75% of lymphangiomas manifest in the head and neck region, with limb and bone involvement observed in only 2% of cases. This case report presents a rare instance of fetal lymphangioma associated with hydrops fetalis, affecting the left lower extremity and abdomen. A 22-year-old secundigravida woman was referred to the gynecology department at 31.2 weeks of gestation. Initial fetal ultrasound revealed a live fetus with a large lymphangioma involving the left lower extremity, gluteal region, and abdomen. Additional ultrasound findings included subcutaneous edema, pericardial effusion, ascites, placentomegaly, and tricuspid regurgitation. Postnatal clinical examination confirmed the diagnosis of lymphatic malformation. Notably, only one other similar case has been reported in the English-language PubMed database. This report adds to the medical literature as a rare instance of prenatally diagnosed lymphangioma-associated hydrops fetalis.
Biopolymers: Histopathologic Case Series of Patients with Permanent Synthetic Fillers Presenting Chronic Granulomatous Reaction and Hypercalcemia
Authors: Pachón Suarez Jaime Eduardo , Tello Victor Zein Rizo , Cifuentes Rocio Carolina Rozo , Cuadros Adriana Marcela Pores , Salazar Marcela C.
Published: October 2024

Background:

Biopolymers, which are diverse and permanent synthetic fillers, are nonbiocompatible allogeneic materials. Their implantation can result in clinical, radiological, and histopathological manifestations that contribute to our understanding of foreign-body-induced human adjuvant disease.

Methods:

We conducted a descriptive observational case series involving 20 patients who underwent open biopolymer removal surgery in the buttocks and lumbosacral regions using the Meticulous Approach Safer and Keeper technique, followed by gluteal reconstruction with autologous tissue. Histopathological analysis was performed. This study was conducted in Bogotá, Colombia, from 2020 to 2023.

Results:

Documented clinical records and histopathological analyses of the 20 patients revealed an inflammatory response that was initially considered healthy. Cytoplasmic vacuolization in reactive adipocytes was observed in all cases, meriting consideration in the differential diagnosis of liposarcoma and suggesting local aggressiveness. One patient showed a positive lymphocytic inflammatory response in the Alcian blue test. Hypercalcemia was present in 30% of the patients, elevated lactate dehydrogenase in 40%, and elevated parathyroid hormone levels in 15%.

Conclusions:

Surgeons should consider measuring lactate dehydrogenase, serum calcium, and parathyroid hormone levels to assess the severity and guide clinical practice. Secondary prevention through the open surgical removal of biopolymers is recommended.
Altered anthropometrics and HA1c levels, but not dyslipidemia, are associated with elevated hs-CRP levels in middle-aged adults: A population-based analysis
Authors: Ashour Laith , Ayesh Layan , Jarrar Zeid , Mishleb Areen , Alenezi Danah , Fateh Moath , Almejaibal Rawan , Madani Nicola Hanna , Dabas Muath Mohammad , Abu Monshar Sama Samer , Hamdan Samar
Published: October 2024

Population-based studies of cardiovascular disease markers, such as hs-CRP, are crucial. However, studies exploring the effect of metabolic indices on hs-CRP while controlling for confounding variables adequately in middle-aged adults are limited. Using Wave 5 data from the National Longitudinal Study of Adolescent Health (Add Health), we examined the impact of various metabolic indices on hs-CRP in adults aged 32-42, controlling for eight allergic and infectious factors that may elevate hs-CRP levels. We used multiple linear regression analysis to determine which factors predict hs-CRP levels after log transformation of the dependent variable. The total number of participants was N = 1839 (weighted N = 1390763), with a mean age of 38.1 (SD = 2.0) and 46.4% having obesity. Among the controlled variables, recent surgery was the only confounder to significantly predict increased hs-CRP levels (P = 0.029, exponentiated estimate (EE) = 1.61; 95% Cl: [1.31-1.91]). Notably, current smoking and altered LDL or TG levels did not show a significant association with hs-CRP levels (P > 0.05). However, a significant increase in hs-CRP levels was observed in females compared to males (P < 0.001, EE = 1.43; 95%Cl: [1.35-1.51]). Similar findings were noted for diabetic HbA1c levels (P = 0.001, EE = 1.6; 95%CL: [1.42-1.78]), high waist circumference (P = 0.015, EE = 1.25; 95%CL: [1.15-1.35]), and grade 3 obesity (P = 0.006, EE = 7.62; 95%CL: [2.86-12.38]). Although not statistically significant, hs-CRP levels exhibited a gradual increase with rising BMI after controlling for other variables. These findings will improve the clinical application of hs-CRP in predicting coronary artery disease, especially in younger adults.
Photobiomodulation Therapy for Serous Pigment Epithelium Detachment in Chronic Central Serous Chorioretinopathy
Authors: Iovino Claudio , Damiano Luciana , Piccirillo Valerio , Testa Francesco , Giannaccare Giuseppe , Simonelli Francesca
Published: October 2024

PURPOSE:

To report a case of giant pigment epithelium detachment (PED) secondary to chronic central serous chorioretinopathy (cCSC) successfully treated with photobiomodulation (PBM).

METHODS:

Case report.

RESULTS:

A 55-year-old man complained a worsening of vision in the left eye (LE) over the last 18 months.

A complete ophthalmological evaluation encompassing best corrected visual acuity (BCVA) measurement, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), fluorescein angiography (FA) and microperimetry (MP) was performed.

SD-OCT showed several small PEDs around the macula in the right eye and a giant macular serous PED with subretinal fluid (SRF) in the LE. FA disclosed multiple hyperfluorescent roundish areas in the posterior pole bilaterally, with a macular pooling in the LE.

A diagnosis of cCSC was made, and patient underwent PBM with one session for week for four weeks, followed by one session bi-weekly for two months.

SD-OCT of the LE showed a gradual flattening of the macular PED at 3 months, with a complete regression of the latter and of the SRF at 6- and 12-month follow up with no residual signs of chorioretinal atrophy on FAF. BCVA improved from 20/80 at baseline to 20/25 at the last follow up, and this functional improvement was further confirmed by MP.

CONCLUSIONS:

PBM can be considered a safe and effective treatment strategy for the management of cCSC with SRF and serous PED.
Corynebacterium striatum
Authors: Tallapalli Jayanth Reddy , Raprolu Sai Sruthi , Kalantri Shreyas , Greene John N.
Published: October 2024

Corynebacterium striatum (C. striatum) is a rapidly emerging multidrug-resistant organism commonly found as a skin and respiratory tract commensal. The first case of C. striatum infection was published in 1980 in a patient with chronic lymphocytic leukemia who had a pleuropulmonary infection. The chemotherapeutic agents used in hematologic malignancies completely deplete neutrophils, making them susceptible to various pathogens such as C. striatum, which are rarely pathogenic. The spectrum of presentation due to C. striatum includes severe bloodstream infections, pneumonia, meningitis, and infective endocarditis. Some of the most common risk factors are prolonged neutropenia with various invasive devices and numerous prophylactic antibiotics. This article aims to present three cases of C. striatum infections in immunocompromised patients at H. Lee Moffitt Cancer Centre. In such rare cases, infection prevention and appropriate antibiotic coverage are the key to preventing such infections.
Symptom Network and Clusters of the Multidimensional Symptom Experience in Patients With Atrial Fibrillation
Authors: Lin Hairong , Luo Huaili , Lin Mei , Li Hong , Sun Dingce
Published: October 2024

Background

The symptom network can provide a visual insight into the symptom mechanisms. However, few study authors have explored the multidimensional symptom network of patients with atrial fibrillation (AF).

Objectives

We aimed to identify the core symptom and symptom clusters of patients with AF by generating a symptom network. Furthermore, we wanted to identify multiple characteristics related to symptom clusters.

Methods

This is a cross-sectional study. A total of 384 patients with AF at Tianjin Medical University General Hospital were enrolled. The University of Toronto Atrial Fibrillation Severity Scale was used to assess AF symptoms. Network analysis was used to explore the core symptom and symptom cluster.

Results

Shortness of breath at rest (r
s = 1.189, r
c = 0.024), exercise intolerance (r
s = 1.116), shortness of breath during physical activity (r
s = 1.055, r
c = 0.022), and fatigue at rest (r
c = 0.020) have the top centrality for strength and closeness. The top 3 symptoms of bridge strength were shortness of breath at rest (r
s = 0.264), dizziness (r
s = 0.208), and palpitations (r
s = 0.207). Atrial fibrillation symptoms could be clustered into the breathless cluster and the cardiac cluster. We have identified multiple factors such as mental health status, left ventricular ejection fraction, heart failure, sex, B-type natriuretic peptide, and chronic obstructive pulmonary disease as significant contributors within the breathless cluster, whereas sex, mental health status, and history of radiofrequency ablation were strongly associated with the cardiac cluster, holding promise in elucidating the underlying mechanisms of these symptoms.

Conclusion

Special attention should be given to shortness of breath at rest as its core and bridging role in patients' symptoms. Furthermore, both the breathless and cardiac clusters are common among patients. Network analysis reveals direct connections between symptoms, symptom clusters, and their influencing factors, providing a foundation for clinicians to effectively manage patients' symptoms.