bluuebunny/crossref_metadata_2025 huggingface dataset:
Drought drives selection for earlier flowering, while pollinators drive selection for larger flowers in annual Brassica rapa
Authors: Rathnayake Kaushalya , Parachnowitsch Amy L
Published: January 2025

Drought-induced changes in floral traits can disrupt plant–pollinator interactions, influencing pollination and reproductive success. These phenotypic changes likely also affect natural selection on floral traits, yet phenotypic selection studies manipulating drought remain rare. We studied how drought impacts selection to understand the potential evolutionary consequences of drought on floral traits. We used a factorial experiment with potted plants to manipulate both water availability (well-watered and drought) and pollination (open and supplemented). We examined the treatment effects on traits of Brassica rapa and estimated phenotypic selection and whether it was pollinator-mediated in these two abiotic conditions. Drought affected plant phenotypes, leading to plants with fewer flowers and ultimately lower seed production. Flowering time did not show variation with watering, but we found the strongest effect of drought on selection was for flowering time. There was a selection for flowering faster in drought but not well-watered conditions. Pollinators instead were the agents responsible for selection on flower size, but we did not find strong evidence that drought effected pollinator-mediated selection. There was a stronger selection for larger flowers in drought compared to well-watered plants, and it could be attributed to pollinators however, there was no significant difference between watering treatments. Our results show the effects of drought are not limited to phenotypic responses and may alter evolution in plants by changing phenotypic selection on traits. The connection between phenotypic plasticity and selection may be important to understand as we found the most variable trait (display size) was not under selection while the trait with different selection in drought (flowering time) did not change in response to drought. Our study highlights the importance of manipulating potential agents of selection, especially to understand fully the potential impacts of components of climate change such as drought.
Unravelling the Efficacy of Internal Quilting Sutures vs Doxycycline Instillations in Preventing Seroma Formation After Gynecomastia Surgery
Authors: Ramasamy Karthik , Alagarasan Abisshek Raj , Gupta Hitesh , Elangovan Anjana , Thakkar Yash , Silwal Kiran , Chatterji Sujoy Kumar , Jammu Sri Latha
Published: January 2025

Background

Seroma frequently presents as a challenge, following gynecomastia correction surgery. This calls for percutaneous aspiration of accumulated fluid, from the iatrogenic dead space. The authors utilized internal quilting sutures and doxycycline instillation to analyze and compare their roles in seroma prevention.

Objectives

To compare the efficacy of intraoperative internal quilting sutures and doxycycline instillation, in preventing seroma formation and recurrence after gynecomastia surgery.

Methods

After local review board and ethics committee approval, the authors conducted this prospective single-center study of 120 gynecomastia patients with Rohrich's Grades I, II, and III, who underwent surgery between October 2023 and March 2024. Those belonging to Rohrich's Grade IV were excluded. Before surgery, the patients were divided into 3 cohorts of 40 individuals using a computerized randomization protocol. Cohort 1 underwent doxycycline instillation, Cohort 2 underwent internal quilting sutures, and no intervention was carried out in Cohort 3. Seroma diagnosis was confirmed clinically and the data were analyzed. All the patients were followed up for a month.

Results

The incidence of seroma formation, volume of seroma fluid removed, and the number of visits for seroma care were statistically found to be the least in the quilting group compared with the doxycycline and control groups. Univariate logistic regression analysis revealed that patients belonging to both doxycycline and control groups showed significantly higher risk for seroma formation with an odds ratio of 4.705 and 6.524, respectively.

Conclusions

Doxycycline instillation was less effective than internal quilting sutures in preventing seroma formation. Internal quilting sutures are a safe effective, and undemanding adjuvant technique to reduce the rate of formation and recurrence of seroma, after gynecomastia surgery.

Level of Evidence: 2
Quantification of variegated Drosophila ommatidia with high-resolution image analysis and machine learning
Authors: Hill Hunter J , Sullivan William , Cooper Brandon S
Published: January 2025

A longstanding challenge in biology is accurately analyzing images acquired using microscopy. Recently, machine learning (ML) approaches have facilitated detailed quantification of images that were refractile to traditional computation methods. Here, we detail a method for measuring pigments in the complex-mosaic adult Drosophila eye using high-resolution photographs and the pixel classifier ilastik [1]. We compare our results to analyses focused on pigment biochemistry and subjective interpretation, demonstrating general overlap, while highlighting the inverse relationship between accuracy and high-throughput capability of each approach. Notably, no coding experience is necessary for image analysis and pigment quantification. When considering time, resolution, and accuracy, our view is that ML-based image analysis is the preferred method.
Scholarship on LGBTQIA+ migrants in the social work field: A scoping review
Authors: Matharu Gurleen Kaur , Tri Thomas , Gonzalez Benson Odessa , Palova Katerina , Kassan Anusha
Published: January 2025

In social work and related practice fields, studies tend to treat LGBTQIA+ and migrant communities as distinct groups, overlooking the unique challenges faced by those at their intersection. This study uses an intersectional lens to examine social work scholarship on LGBTQIA+ migrants in order to map trends and identify gaps. We examined scholarship along various dimensions, including (1) geography, temporality, and methodology; (2) migrant and gender and sexuality identities; and (3) a range of topics. Findings suggest that literature is skewed towards health and mental health as a topic, qualitative methods, and the Global North as the location of first authors and research sites. Economic migrants receive more attention than vulnerable groups such as asylum seekers and undocumented migrants. Regarding sexual and gender identities, the bulk of literature is focused on men who have sex with men, followed by gay, lesbian, and bisexual identities. Also, the number of identities examined has greatly increased over time, while LGBTQIA+ migrant youth emerged as understudied. Findings in this scoping review point to heightened intersectional perspectives in the study of LGBTQIA+ migrants in the social work field.
Oral mucosal papules in an immunosuppressed girl
Authors: Peirano Felipe , Rusiñol Lluís , Iznardo Helena , Carmona-Rocha Elena , Puig Lluís , Roé Esther
Published: January 2025

We report the case of a 7-year-old girl from Peru with a history of acute myeloblastic leukaemia. She presented with asymptomatic, white, papillomatous papules on the upper and lower lip mucosa and palate.
A review of secondary intention healing in dermatology and dermatological surgery: part 1
Authors: Potluru Aparna , Pawlik Olga , Barlow Richard , Veitch David , Wernham Aaron
Published: January 2025

Secondary intention healing (SIH) describes wounds healing from the base upwards, without direct closure. This starts with granulation of the wound, followed by re-epithelialization and contraction. The surgeon and patient need to weigh up the advantages and disadvantages of SIH vs. other reconstruction methods. There are limited studies directly comparing SIH with skin grafts; however, SIH looks to be a robust alternative in specific settings. Well-established sites for SIH include concave areas such as the nose, eye, ear and temple, as these areas give rise to the best cosmetic outcomes. However, SIH has proven to be a successful repair method in several convex locations, including the dorsa of the hands, digital extremities, scalp, lips and eyelids. SIH can be supplemented by other surgical techniques, including purse-string sutures and postoperative de-epithelialization.
Safety, Efficacy, and Pharmacokinetics of Daily Optimized Doses of Rifampicin for the Treatment of Tuberculosis: A Systematic Review and Bayesian Network Meta-Analysis
Authors: Espinosa-Pereiro Juan , Aguiar Ana , Nara Eva , Medina Angelica , Molinas Gladys , Tavares Margarida , Tortola Teresa , Ghimire Samiksha , Alfenaar Jan-Willem C , Sturkenboom Marieke G G , Magis-Escurra Cecile , Sánchez-Montalva Adrián , Barros Henrique , Duarte Raquel
Published: January 2025

Background

Higher than standard doses of rifampicin could improve the treatment outcome of drug-susceptible tuberculosis (TB) without compromising the safety of patients.

Methods

We performed a systematic review of prospective clinical studies including adults with pulmonary and extrapulmonary TB receiving rifampicin doses above 10 mg/kg/day. We extracted the data on overall adverse events (AE), hepatic AE, sputum culture conversion (SCC) at week 8, recurrence, mortality, and pharmacokinetics. We performed a Bayesian network meta-analysis (NMA) using a random-effects model.

Results

In 19 studies, 2033 out of 3654 participants received rifampicin doses higher than 10 mg/kg/day. The NMA showed an increased risk of overall and hepatic AE for the 40 mg/kg/day dose (risk ratio [RR] 4.8, 95% credibility interval [CrI]: 1.1, 25, and 15.00; 95% CrI: 1.1, 58.0, respectively), but no other doses, including 50 mg/kg/day showed such an increase. Increasing doses improved sputum culture conversion at week 8 (RR 1.3, 95% CrI: 1.1, 1.7 for SCC with 35 mg/kg/day).

Conclusions

Optimal doses of rifampicin may be between 25 and 35 mg/kg/day, but should be tailored at the individual or, at least, at the population level.
Impact of COVID-19 pandemic on the incidence and prevalence of postural orthostatic tachycardia syndrome
Authors: Dulal Dharmindra , Maraey Ahmed , Elsharnoby Hadeer , Chacko Paul , Grubb Blair
Published: January 2025

Background

Individuals recovering from COVID-19 infection have reported experiencing symptoms of postural orthostatic tachycardia syndrome (POTS). These observations have raised concerns about COVID-19 as a significant precipitating factor in the development of post-viral POTS. Given the increasing number of POTS cases reported after COVID-19, we sought to examine the baseline characteristics of POTS patients before and after COVID-19.

Methods

We conducted an interrupted time series analysis on data obtained from the TriNetX database, which included a cohort of 65 141 065 patients aged 18 and older across 64 healthcare organizations. Monthly data on incidence rates (IR), incidence cases (IC), and prevalence cases (PC) of POTS were collected from January 2018 to June 2024, with 1 March 2020 defined as the cutoff date for pre- and post-COVID analysis.

Results

There was a significant increase in the IR of POTS post-COVID (P < 0.0001), with the IR increasing from 1.42/1000 000 to 20.3/1000 000 cases per person-year. Similarly, the monthly IC trend showed a significant rise from 4.21 to 22.66 cases (P < 0.001). The month-to-month prevalence showed an initial decline after COVID with a robust increase starting January 2023. Additionally, the prevalence of autonomic nervous system disorders and related comorbidities significantly decreased in the post-COVID cohort.

Conclusion

Our findings demonstrate a significant increase in the incidence of POTS following the COVID-19 pandemic, suggesting a potential association between COVID-19 infection and the development of post-viral POTS. Future research should explore the underlying mechanisms and treatment strategies for POTS in the context of post-COVID recovery.
Telomere-to-telomere genome and resequencing of 254 individuals reveal evolution, genomic footprints in Asian icefish, Protosalanx chinensis
Authors: Zhou Yanfeng , Wang Chenhe , Wang Binhu , Xu Dongpo , Zhang Xizhao , Ge You , Jiang Shulun , Tang Fujiang , Chen Chunhai , Li Xuemei , Jian Jianbo , You Yang
Published: January 2025

The Asian icefish, Protosalanx chinensis, has undergone extensive colonization in various waters across China for decades due to its ecological and physiological significance as well as its economic importance in the fishery resource. Here, we decoded a telomere-to-telomere (T2T) genome for P. chinensis combining PacBio HiFi long reads and ultra-long ONT (nanopore) reads and Hi-C data. The telomere was identified in both ends of the contig/chromosome. The expanded gene associated with circadian entrainment suggests that P. chinensis may exhibit a high sensitivity to photoperiod. The contracted genes’ immune-related families and DNA repair associated with positive selection in P. chinensis suggested the selection pressure during adaptive evolution. The population genetic analysis reported the genetic diversity and genomic footprints in 254 individuals from 8 different locations. The natural seawater samples can be the highest diversity and different from other freshwater and introduced populations. The divergent regions’ associated genes were found to be related to the osmotic pressure system, suggesting adaptations to alkalinity and salinity. Thus, the T2T genome and genetic variation can be valuable resources for genomic footprints in P. chinensis, shedding light on its evolution, comparative genomics, and the genetic differences between natural and introduced populations.
Pseudo-prospective earthquake forecasting experiment in Italy based on temporal variation of the b-value of the Gutenberg–Richter law
Authors: Biondini E , D'Orazio F , Lolli B , Gasperini P
Published: January 2025

We present the BVAL method, designed to forecast potentially damaging earthquakes (Mw ≥ 5.0) in Italy based on temporal variations of the b-value of the Gutenberg–Richter frequency–magnitude distribution. The b-value is used as an indicator of stress within the Earth's crust, with lower b-values associated with higher stress levels and an increased likelihood of significant seismic events. This method issues alarms when the b-value falls below a critical threshold. It is optimized using the HOmogenized instRUmental Seismic catalogue data from 1990 to 2004 and validated pseudo-prospectively using data from 2005 to 2022. Our analysis uses the recently developed b-positive (b+) method to compute the b-value from magnitude differences, providing resilience against data incompleteness. We compare the performance of the BVAL method with two established models: the Epidemic Type Aftershock Sequence (ETAS) model, which forecasts earthquake rates based on the epidemic principle that each shock triggers subsequent shocks, and the FORE model, which relies on the occurrence of strong foreshocks. Additionally, we evaluate two ensemble models that combine BVAL and FORE through additive (EADD) and multiplicative (EMUL) strategies to balance false alarms and missed events. The EADD model declares an alarm when either BVAL or FORE signals it, while the EMUL model triggers alarms only when both methods agree. We assess the predictive efficiency of these models using the area skill score, derived from Molchan diagrams, which plot the miss rate against the fraction of space-time occupied by alarms. Our results demonstrate that BVAL is less effective than FORE and ETAS at high space-time fractions, but it outperforms ETAS at low fractions ($\tau \ $ < 2–4 per cent), indicating its potential utility in scenarios where minimizing false alarms is critical. This comprehensive comparison highlights the strengths and limitations of each method, suggesting that integrating multiple forecasting strategies can enhance the reliability of earthquake preparedness and response efforts in Italy.
Honeybee toxicity of pesticides used in United States maize and soybean production, 1998–2020
Authors: Kniss Andrew R , De Stefano Andrea , Arnold Elyssa , Douglass Cameron , Myers Clayton , Paisley-Jones Claire , Ranville Michelle
Published: January 2025

Pesticides are widely used around the world and have demonstrated benefits to crop production. However, pesticides have also been associated with negative impacts to nontarget organisms, including pollinators. Here, we combined pesticide usage and toxicity data to create a toxicity index, which shows that pesticide hazard to honeybees (Apis mellifera) has changed substantially in U.S. maize (Zea mays) and soybean (Glycine max) production between 1998 and 2020. To reduce potential risks to honeybees and increase the eco-efficiency of crop production, efforts should be made to refine management strategies for pests that contribute most to the honeybee toxicity index. In maize, Coleoptera and Lepidoptera pests drive pesticide usage most responsible for hazard to honeybees, although the relative hazard from targeting those pests has decreased over time. In soybean, hemipteran pests were the largest relative contributor to insecticide honeybee hazard. Specific pests that contributed to honeybee toxicity hazard included corn rootworm species (Diabrotica spp.), silk-eating insects, and cutworms in maize, and stink bugs (family Pentatomidae) and aphid species (Family Aphididae) in soybean. We combined crop yield data with the toxicity index to quantify the eco-efficiency, a measure of crop yield per unit of toxicity hazard. While crop yield for both maize and soybean increased steadily throughout the study period, eco-efficiency decreased in both crops between 2012 and 2020, suggesting increases in crop yield have failed to keep pace with increases in insecticide hazard to honeybees.
Efficacy of cleaning, disinfection, and sterilization modalities for addressing infectious drug-resistant fungi: a review
Authors: Garvey Mary , Kremer Terra A , Rowan Neil J
Published: January 2025

This is a timely and important review that focuses on the appropriateness of established cleaning, disinfection, and sterilization methods to safely and effectively address infectious fungal drug-resistant pathogens that can potentially contaminate reusable medical devices used in healthcare environment in order to mitigate the risk of patient infection. The release of the World Health Organization (WHO) fungal priority pathogen list (FPPL) in 2022 highlighted the public health crisis of antimicrobial resistance (AMR) in clinically relevant fungal species. Contamination of medical devices with drug-resistant fungal pathogens (including those on the FPPL) in healthcare is a rare event that is more likely to occur due to cross-transmission arising from lapses in hand hygiene practices. Established disinfection and sterilization methods decontaminate fungal pathogens on single-use and reusable medical devices; however, there are assumptions that reusable devices destined for semi-critical use are appropriately cleaned and do not harbour biofilms that may undermine the ability to effectively decontamination these type devices in healthcare. International standards dictate that manufacturer’s instructions for use must provide appropriate guidance to healthcare facilities to meet safe reprocessing expectations that include addressing drug-resistant fungal pathogens. Increased environmental monitoring and vigilance surrounding fungal pathogens in healthcare is advised, including adherence to hand hygiene/aseptic practices and appropriate cleaning encompassing the simplification of reusable device features for ‘ease-of-reach’. There are emereging opportunities to promote a more integrated multiactor hub approach to addressing these sophisticated challenges, including future use of artificial intelligence and machine learning for improved diagnostics, monitoring/surveillance (such as healthcare and wastewater-based epidemiology), sterility assurance, and device design. There is a knowledge gap surrounding the occurrence and potential persistence of drug-resistant fungal pathogens harboured in biofilms, particularly for ascertaining efficacy of high-level disinfection for semi-critical use devices.
Assessing the lethal effects of pesticide residue exposure on beneficial parasitoids and their host, Halyomorpha halys (Stål) (Hemiptera: Pentatomidae)
Authors: Luo Zheng-Yu , Gao Li-Ping , Li Wen-Jing , Chen Ju-Hong , Ali Muhammad Yasir , Zhang Feng , Li Feng-Qi , Wang Xiang-Ping , Zhang Jin-Ping
Published: January 2025

Chemical control is currently the main strategy for managing brown marmorated stink bug, Halyomorpha halys (Stål). However, chemical pesticides can harm nontarget species, including natural enemies of H. halys. Pesticides with high toxicity to H. halys and low toxicity to its parasitoids need to be identified to support H. halys management. This is not only for natural biological control but also for preemptive classical biological control of H. halys by parasitoids. Here, we assessed the contact toxicity of residues of eight insecticides against H. halys and three of its main parasitoid species (Anastatus japonicus Ashmead (Hymenoptera: Eupelmidae), Trissolcus japonicus Ashmead (Hymenoptera: Scelionidae), Trissolcus cultratus Mayr (Hymenoptera: Scelionidae)). This study aims to provide valuable insights for preemptive classical biological control of H. halys using these parasitoids. Our results showed that A. japonicus exhibited higher tolerance to the tested pesticides, while T. japonicus was the most sensitive species. Among the pesticides, chlorantraniliprole had the lowest overall impact on all three parasitoid species. Additionally, acetamiprid, azadirachtin, and rotenone were found to be harmless to A. japonicus. Acetamiprid, however, was slightly harmful to T. cultratus. The remaining pesticides showed moderate to significant harmful effects on the parasitoids. For H. halys adults and fifth instars, the pesticides tested caused no mortality within the 24 h exposure. However, young nymphs were susceptible to the tested pesticides. Fenpropathrin had the highest toxicity to H. halys, killing 83.3%, 52.8%, and 19.4% of second, third, and fourth instars in a 24 h exposure. Fenpropathrin, acetamiprid, cyfluthrin, azadirachtin, and dinotefuran were all slightly harmful to the first instar nymphs. The other pesticides were harmless to H. halys in a 24 h exposure. Halyomorpha halys mortality increased with the contact time with the residue. Mortality of fourth and fifth instars of H. halys was >70% for fenpropathrin, cyfluthrin, dinotefuran, abamectin-aminomethyl, and acetamiprid if exposure continued for 7 d. Acetamiprid was effective in controlling H. halys nymphs but exhibited varying levels of toxicity towards the three tested parasitoid species, depending on the residue age and exposure time. Azadirachtin showed lower overall toxicity to beneficial insects, suggesting that these materials could be used to manage H. halys while minimizing harm to key beneficial species.
A comparison of shrinkage estimators of the cosmological precision matrix
Authors: Looijmans Marnix J , Wang Mike (Shengbo) , Beutler Florian
Published: January 2025

The determination of the covariance matrix and its inverse, the precision matrix, is critical in the statistical analysis of cosmological measurements. The covariance matrix is typically estimated with a limited number of simulations at great computational cost before inversion into the precision matrix; therefore, it can be ill-conditioned and overly noisy when the sample size n used for estimation is not much larger than the data vector dimension. In this work, we consider a class of methods known as shrinkage estimation for the precision matrix, which combines an empirical estimate with a target that is either analytical or stochastic. These methods include linear and non-linear shrinkage applied to the covariance matrix (the latter represented by the so-called NERCOME estimator), and the direct linear shrinkage estimation of the precision matrix which we introduce in a cosmological setting. By performing Bayesian parameter inference and using metrics like matrix loss functions, the Kullback–Leibler divergence and the eigenvalue spectrum, we compare their performance against the standard sample estimator with varying sample size n. We have found the shrinkage estimators to significantly improve the posterior distribution at low n, especially for the linear shrinkage estimators either inverted from the covariance matrix or applied directly to the precision matrix, with an empirical target constructed from the sample estimate. Our results are particularly relevant to the analyses of Stage-IV spectroscopic galaxy surveys such as the Dark Energy Spectroscopic Instrument and Euclid, whose statistical power can be limited by the computational cost of obtaining an accurate precision matrix estimate.
Photometry of (162173) Ryugu and its artificial crater as inferred by Hayabusa2/ONC images
Authors: Longobardo A , Angrisani M , Palomba E , Dirri F , Yokota Y , Kouyama T ,   the Hayabusa2/ONC Team
Published: January 2025

The JAXA/Hayabusa2 rendezvoused with the (162 173) Ryugu asteroid from June 2018 to November 2019, performing an artificial impact experiment on 5th April 2019. The goal of this work is to study the photometric properties’ variation of the target area (latitude 7–10°N; longitude 303–305°E) after the artificial impact experiment. This is done by applying an empirical method based on the statistical analysis of the Optical Navigation Camera (ONC)’s data set (in particular, of the v band, centred at 0.55 $\mu$m), similar to that applied to other asteroids explored by space missions and to the NIRS3 data set of Ryugu. The method was firstly applied on the entire data set acquired between March and April 2019, covering most of the Ryugu surface. The retrieved average phase function of Ryugu is very similar to that obtained on the NIRS3 data set, according to the similar visible and near-infrared albedo values. Nevertheless, this phase function is flatter than other asteroids belonging to the same Ryugu taxonomic class. This can be attributed to the higher spatial resolution of Hayabusa2 observations, which flattens the phase function of dark asteroids by minimizing the effects of shadowing, as confirmed by photometric studies of other asteroids. Then, the photometric properties of the artificial impact crater area revealed a slight phase function steepening and narrowing after the impact: this could indicate that the exposed surface has a larger roughness and more porous particles.
A pilot study to quantify and describe personal social networks in patients with glioblastoma
Authors: Rhee John Y , Mastrangelo Carissa , Miller Paul J , Youssef Gilbert , Tentor Zachary , Rothfeld-Wehrwein Zachary R , Dhongade Vrushali A , Nakhate Vihang , Batchelor Tracy , Dhand Amar
Published: January 2025

Background

Patients with glioblastoma experience high physical and psychosocial symptom burden. Poor social relationships have been shown to increase the risk of neurologic illnesses and decline, and conversely, strong personal social networks (PSN) have been shown to reduce the risk of mortality and improve quality of life. The aim of this pilot study is to determine the feasibility of measuring PSN in glioblastoma patients.

Methods

We recruited 25 adult glioblastoma patients between the initial diagnosis and the first cycle of adjuvant chemotherapy from March to September 2023 in the outpatient neuro-oncology clinic and adapted PERSNET, a quantitative PSN assessment tool, to this population. We collected demographics, tumor measures, treatment courses, and the European Organization for Research and Treatment of Cancer QOL for Patients with Brain Tumors (EORTC QLQ-BN20) and conducted qualitative interviews.

Results

The average age was 64.5 years old, 56% were female, and 84% had a Karnofsky Performance Status of 70 or higher. Patients had large network sizes (total size of patient’s PSN; mean = 8.8). Participants stressed the importance of social support and how different people filled different roles in their oncology care. Behavioral and/or cognitive changes resulted in delayed presentation, and children, especially daughters, were important in advocating for presentation to the hospital.

Conclusion

This is the first proof-of-concept study showing that PSN can be measured in patients with glioblastoma. Qualitative data showed that patients felt social support was very important, and different people in their networks addressed different domains of care: physical, emotional, and logistical.
Severe Non–Donor-Derived Lymphocytic Choriomeningitis Virus Infection in 2 Solid Organ Transplant Recipients
Authors: Sayyad Leanna E , Smith Kami L , Sadigh Katrin S , Cossaboom Caitlin M , Choi Mary J , Whitmer Shannon , Cannon Debi , Krapiunaya Inna , Morales-Betoulle Maria , Annambhotla Pallavi , Basavaraju Sridhar V , Ruberto Irene , Kretschmer Melissa , Gutierrez Nalleli , Zabel Karen , Austin Connie , Sandoval Edith , Servellita Venice , Foresythe Abiodun , Sumimoto Nanami , Aqel Bashar A , Khamash Hasan A , Jadlowiec Carrie C , Grys Thomas E , Jaramillo Andres , Grill Marie F , Montgomery Joel M , Shoemaker Trevor , Klena John D , Chiu Charles Y , Vikram Holenarasipur R
Published: January 2025

Background

Lymphocytic choriomeningitis virus (LCMV) infection in immunocompromised hosts can result in disseminated disease, meningoencephalitis, and death. Published cases in transplant recipients have been traced to transmission from infected donors. We report 2 cases of serious, non–donor-derived LCMV infection in solid organ transplant recipients.

Methods

Initial identification of LCMV infection was done by using metagenomic next-generation sequencing (mNGS). Subsequent evaluations and confirmatory testing involved molecular diagnostics, serology, and phylogenetic analysis. A detailed epidemiologic investigation was conducted.

Results

LCMV was detected by mNGS in 2 solid organ transplant recipients from distinct donors. A heart transplant recipient (from donor 1) died of progressive, disseminated LCMV infection, while a kidney transplant recipient (from donor 2) with LCMV meningoencephalitis survived. A multistate laboratory and epidemiologic investigation of both donors and all their organ recipients was initiated. Postmortem samples were obtained from both donors, and pretransplant and/or posttransplant samples were obtained from 5 of the 6 organ recipients. mNGS, serologic, and real-time reverse-transcription polymerase chain reaction testing confirmed LCMV infection in both solid organ transplant recipients. Epidemiologic investigation revealed significant pretransplant rodent exposures for both LCMV-infected recipients. Laboratory studies for the other organ recipients from both donors were negative for LCMV infection.

Conclusions

Our investigations suggest that LCMV infection in 2 solid organ transplant recipients originated from rodent exposure preceding transplantation and were not donor derived. Although uncommon, healthcare providers should be aware of LCMV-associated serious and life-threatening illness in immunocompromised hosts. Diagnostic modalities are limited to reference laboratories.
Correlates of Protection Against Symptomatic COVID-19: The CORSER 5 Case–Control Study
Authors: Beeker Léopold , Obadia Thomas , Bloch Emma , Garcia Laura , Le Fol Manon , Charmet Tiffany , Arowas Laurence , Artus Rémy , Cheny Olivia , Cheval Dorian , Dahoumane Yanis , Delhaye Maurine , Ergen Delal , Essaidani Mariem , Fanaud Christine , Fernandes Pellerin Sandrine , Jolly Nathalie , Laude Hélène , Roux Emmanuel , Samson Marine , Sangari Linda , Ungeheuer Marie-Noëlle , Vacant Sophie , Zayoud Ayla , Donnadieu Françoise , Pelleau Stéphane , Galmiche Simon , Fontanet Arnaud , White Michael
Published: January 2025

Background

Establishing correlates of protection often requires large cohorts. A rapid and adaptable case–control study design can be used to identify antibody correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in serum and saliva.

Methods

We designed a case–control study to compare antibody levels between cases of SARS-CoV-2 infection within 5 days of symptom onset and uninfected controls. Controls were matched on age, number of coronavirus disease 2019 vaccine doses, time since last dose, and past episodes of infection. We quantified anti-SARS-CoV-2 and seasonal coronavirus immunoglobulin (Ig) G in serum and saliva at inclusion, 1 month, and 6 months.

Results

We included 90 cases and 62 controls between February and September 2022. A boost and decay pattern of serum antibodies was observed in cases at 1 and 6 months, respectively, but not in controls. Anti-SARS-CoV-2 antibody levels were significantly higher in controls at inclusion both in serum (particularly antinucleocapsid IgG: 4.14 times higher compared with cases; 95% CI, 2.46–6.96) and saliva (particularly antispike for Delta variant IgG: 4.89 times higher compared with cases; 95% CI, 2.91–9.89). Saliva antibodies generally outperformed serum antibodies for case/control differentiation.

Conclusions

In this case–control study, we provided evidence of correlates of protection of anti-SARS-CoV-2 IgG in saliva and serum, with saliva antibodies often outperforming serum. The finding that antibodies in saliva are a better correlate of protection than antibodies in serum may inform vaccine development by highlighting the importance of robust induction of mucosal immune responses. This study design may be used during future epidemics for the prompt assessment of correlates of protection.
Navigating antiphospholipid syndrome: from personalized therapies to cutting-edge research
Authors: Kortright-Maldonado Karen , Reyes-Torres Bruno Eduardo , Cabrera-Lopez Lilian Stephany , Rodríguez-Henríquez Pedro , Tenorio-Aguirre Erika Karina , Martínez-Sánchez Froylan D
Published: January 2025

APS is an autoimmune disorder characterized by thrombosis and pregnancy complications, primarily driven by aPLs such as LA, aCL and anti-β2 glycoprotein I (a-β2GPI). Despite advances in anticoagulation therapies, managing refractory APS cases remains challenging. Emerging therapies, including rituximab, eculizumab and HCQ, show potential in addressing the underlying mechanisms of APS. Additionally, research into genetic and environmental factors, particularly the gut microbiome’s role through molecular mimicry, suggests new therapeutic pathways. Diagnostic advancements, such as the adjusted Global Antiphospholipid Syndrome Score (aGAPSS), metabolomic profiling and MRI, have improved risk stratification and early detection. Non-traditional biomarkers like anti-phosphatidylserine/prothrombin (aPS/PT) and anti-Domain I antibodies further enhance risk assessment. Future research should aim to validate these approaches, optimizing patient outcomes and minimizing long-term APS complications.
Predicting Blood Loss in Aneurysmal Bone Cyst Surgery
Authors: Syed Akbar N. , Talwar Divya , Kell David , Arkader Alexandre
Published: January 2025

Background:

Preoperative estimation of intraoperative blood loss is essential for its management and literature is lacking with respect to factors influencing blood loss in aneurysmal bone cysts (ABC) surgery. The purpose of this study is to identify risk factors and predictors for blood loss in ABC surgery.

Methods:

An IRB-approved retrospective review was performed from 2011 to 2021 at a pediatric tertiary care center. A database identified pediatric patients (<18y old) undergoing surgical curettage and bone grafting for ABC. Lesions in the skull and ribs were excluded. Data collected included demographic data (age, sex), Enneking stage, Capanna type for limb lesions, lesion location, lesion volume (calculated as Transverse × Craniocaudal × Anteroposterior), and history of pathologic fracture before surgical management. Blood loss was recorded as (1) absolute blood loss during surgery and (2) relative loss of total blood volume for individual patients based on their weight and age. Statistical testing was performed using bivariate statistics (Mann-Whitney, Kruskal-Wallis) and multivariate regression analysis.

Results:

We identified a total of 102 lesions in 101 patients with a mean age of 11.5 years at the time of surgery (range 1.0 to 18.2). Absolute blood loss and relative blood loss increased significantly (P<0.001 for both) with respect to lesion volume. Risk factors for absolute and relative blood loss were identified as type 3 Enneking lesions and those located at the spine/pelvis for all lesions (P<0.05), while for lesions in the limbs, those located in the shoulder/hip were identified as a risk factor for both absolute and relative blood loss. In multivariate analysis, age, lesion location, and lesional volume were predictive of absolute blood loss (P<0.05). While multivariate analysis for relative blood loss identified lesion location and lesional volume of >100 mm3 (P=0.004) as predictors.

Conclusion:

Our study enhances the understanding of intraoperative blood loss in ABC surgery. Findings from this study help identify patients at risk of increased blood loss. Age and lesion volume are factors to consider before estimating blood loss in ABC surgery. Surgeons should be cautious of bleeding risk associated with enneking type 3 lesions, spine/pelvic lesions, and locations precluding the use of a tourniquet.

Level of Evidence:

Level III.
Paeoniflorin sensitizes imatinib mesylate-resistant chronic myeloid leukemia cells via the inhibition of Cyr61 production
Authors: Song Yanfang , Luo Li , Lin Zhen , Zhang Taigang , Li Zhaozhong , Cao Yinping , Zhu Xianjin
Published: January 2025

Imatinib mesylate (IM) is a first-line therapy for chronic myeloid leukemia (CML) and exhibits good therapeutic effects, but not in all patients with CML owing to drug resistance. Our previous study showed that Cyr61 plays a key role in IM resistance in CML cells. Paeoniflorin (PF) is a bioactive compound isolated from the traditional Chinese medicine Paeonia lactiflora Pall that displays anticancer activity. Little is, however, known regarding the role of PF in IM-resistant CML cells. This study aimed to evaluate whether PF could decrease Cyr61 production and improve IM-resistant CML cell sensitivity to IM and to investigate the underlying mechanisms. CML cell lines (K562 and KCL22) and IM-resistant cell lines (K562G and KCL22R) were used as CML study models. Cyr61 expression was assessed in both parental and IM-resistant CML cells by western blotting, real-time quantitative PCR , and ELISA. Lentiviral vectors were used to induce the knockdown of Cyr61 expression, followed by a comprehensive evaluation of cell proliferation and apoptosis. The results showed that PF decreased the production of Cyr61 in the presence of IM by inhibiting extracellular regulated protein kinases 1/2 activation. PF significantly decreased the IC50 value of IM and increased IM-induced apoptosis of IM-resistant CML cells. Importantly, PF also improved the sensitivity of CML cells to bosutinib and dasatinib via inhibition of Cyr61 production. In conclusion, we report for the first time that PF may effectively improve the sensitivity of IM-resistant CML cells to IM, bosutinib, and dasatinib, at least in part, by subsequently downregulating Cyr61.
SIAD onset in a patient affected by metastatic melanoma treated with immune checkpoint inhibitors: the role of nivolumab treatment
Authors: Bassi Vincenzo , Apuzzi Valentina , Vanella Vito , Facchini Bianca Arianna , Fattoruso Olimpia
Published: January 2025

Malignant melanoma is a broad and heterogeneous class of malignant tumors derived from melanocytes and classified as cutaneous (skin), uveal, and mucosal melanoma. The incidence of melanoma has increased worldwide in recent decades. Surgery remains the mainstay of treatment, but a dramatic change in systemic treatment occurred when immune checkpoint inhibitors (ICIs) entered the therapeutic armamentarium for metastatic melanoma. Pembrolizumab and nivolumab, both anti-programmed death antibodies, demonstrated superiority over standard therapies with a 5-year survival rate. Toxicities resulting from ICIs have an autoimmune etiology and can affect any organ system. We then present a case of a patient with metastatic melanoma treated with an ICI strategy who developed endocrine toxicity such as the syndrome of inappropriate antidiuresis (SIAD). A previous case report concerning an anti-programmed death ligand 1 antibody suggests that this pathway may be involved in the development of SIAD.
Vitiligo-like hypopigmentation secondary to adjuvant checkpoint inhibitor therapy in patients with resectable stage III melanoma: a cohort from two tertiary hospitals
Authors: Pozuelo-Ruiz Mónica , de Unamuno-Bustos Blanca , Palacios-Diaz Rodolfo D. , Blanes-Martínez María del Mar , Juan-Carpena Gloria , Martínez-Banaclocha Natividad , Botella-Estrada Rafael
Published: January 2025

Vitiligo-like hypopigmentation induced by immune checkpoint inhibitors (ICIs) has been largely associated with improved survival outcomes in metastatic melanoma. However, its development during adjuvant ICI therapy and its role as a prognostic factor in this setting remain unclear. We aimed to describe ICI-induced vitiligo in a cohort of patients with resected stage III melanoma treated with adjuvant ICI and to identify differences in progression-free survival (PFS) and distant metastasis-free survival (DMFS) between those who developed vitiligo and those who did not. Patients and data were collected from two institutions, both retrospectively and prospectively, from January 2018 to February 2024. Patients were divided into ‘vitiligo’ and ‘non-vitiligo’ groups for comparisons. Of 40 patients, 22.5% developed ICI-induced vitiligo [median follow-up: 23 months (1–73)]. Treatments received were nivolumab (70%) and pembrolizumab (30%). Fifty-five percent of the patients completed 1 year of treatment, 37.5% discontinued and 7.5% were still ongoing. Vitiligo and non-vitiligo groups differed in the cause of treatment discontinuation (severe toxicity in vitiligo vs. progression in non-vitiligo, P = 0.005) and the occurrence of progression (none in vitiligo vs. 52% in non-vitiligo, P = 0.001). Survival analyses showed longer PFS in vitiligo group (P = 0.013) and no differences in DMFS (P = 0.111). ICI-induced vitiligo typically affected photo-exposed areas, with a median time to onset of 4 months (1–27). These preliminary results on ICI-induced vitiligo in adjuvant treatment are in agreement with those reported in advanced melanoma treatment, so its development in the adjuvant setting could be a sign of good prognosis as well.
State of the art endocrine treatments for patients diagnosed with endometrial cancer in 2025
Authors: Musa Fernanda B. , Moore Kathleen N. , Podder Vivek , Slomovitz Brian M.
Published: January 2025

Purpose of review

Endometrial cancer (EC) is rising in incidence, particularly in younger, premenopausal women, due to increasing rates of obesity and delayed childbearing. This review evaluates current and emerging endocrine therapies, with a focus on fertility-preserving approaches for early-stage EC and treatment options for advanced or recurrent disease.

Recent findings

Fertility-sparing endocrine therapies, such as medroxyprogesterone acetate, megestrol acetate, and levonorgestrel-releasing intrauterine devices, achieve high response rates but carry recurrence risks. Biomarkers, including progesterone receptor status and molecular subtyping, are improving patient selection and outcomes. In advanced EC, single-agent and combination endocrine therapies with agents like selective estrogen receptor modulators, selective estrogen receptor down-regulators (SERDs), and aromatase inhibitors show efficacy, especially in hormone receptor-positive disease. Newer agents, including next-generation SERDs and proteolysis-targeting chimeras, hold potential for treating resistant cases.

Endocrine therapy offers a well tolerated alternative to chemotherapy in selected EC patients, particularly those with hormone-sensitive tumors. Advances in molecular profiling and the development of novel endocrine agents are refining treatment strategies, supporting endocrine therapy’s continued role in managing EC across various stages.
Platelet distribution width—a prognosis marker in patients with chronic heart failure
Authors: Ana Neves  , Gouveia Rita , Madureira Sérgio , Elias Catarina , Ribeirinho-Soares Pedro , Soares-Carreira Marta , Pereira Joana , Almeida Jorge , Lourenço Patrícia
Published: January 2025

Background:

Increased levels of platelet distribution width (PDW) can predict cardiac death and infarction recurrence in acute myocardial infarction. PDW appears to be a prognosis marker in acute heart failure (HF); however, its impact on chronic HF is still unknown. We investigated the impact of PDW on chronic HF.

Methods:

We retrospectively analyzed outpatients with chronic HF with left ventricular systolic dysfunction (LVSD) from January 2012 to May 2018. Patients with no data on PDW levels or with preserved or recovered ejection fraction were excluded. The primary end point was all-cause mortality. Multivariable Cox regression analysis was used to evaluate the association between PDW and mortality. A multivariate model was built adjusting for age, sex, comorbidities, brain-type natriuretic peptide, New York Heart Association (NYHA) class, evidence-based therapy, and severity of LVSD.

Results:

In our cohort of 766 patients, 65.7% were male, the mean age was 70 years, and 35.4% were in NYHA class I; 38.3% had diabetes mellitus, 51.4% had severe LVSD, and 3.9% had an inflammatory or autoimmune disease. The median (interquartile range) PDW was 13.5 (12.1–14.9) fL. During a median follow-up of 49 (30–79) months, 372 patients (48.6%) died. Patients with PDW ≥ 14.3 fL presented a multivariate-adjusted higher risk of all-cause death than those with lower values (hazard ratio: 1.32, 95% confidence interval [CI]: 1.05–1.64, P = .2).

Conclusions:

Patients with PDW ≥14.3 fL (upper tercile for PDW) presented a multivariate-adjusted 32% (95% CI: 5–64%) higher risk of all-cause death than those with lower values. PDW can help clinicians stratify patients with chronic HF; it is a practical, inexpensive, and widely available parameter.