bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise Intensity and Cardiac Disease Development in carriers of Titin variants
Authors: Savonitto Giulio , Paldino Alessia , Setti Martina , Berra Arianna , Radesich Cinzia , Perotto Maria , Del Mestre Eva , Cittar Marco , Tavcar Irena , Ribichini Flavio Luciano , Barbati Giulia , Gigli Marta , Stolfo Davide , Dal Ferro Matteo , Merlo Marco , Sinagra Gianfranco
Published: February 2025

Aims

While the exacerbating effect of physical exercise and its correlation with arrhythmic outcomes have been demonstrated for Arrhythmogenic Right Ventricular Cardiomyopathy, the impact of physical exercise on other forms of cardiomyopathies is poorly characterized. This study aimed to investigate the relationship between lifelong exercise intensity and the development of cardiac manifestations in subjects carrying a Likely Pathogenic (LP) or Pathogenic (P) truncating variant of titin (TTNtv).

Methods

TTNtv carriers – patients and family members – were interviewed regarding their exercise habits from birth until diagnosis (type of activity, hours/week, weeks/months, months/years, and number of years of exercise). Those engaging in ≥4 hours of vigorous exercise per week (equivalent to ≥1440 METs×minutes/week) for a minimum of 6 years were classified as Athletes. All others were classified as Non-athletes.

The correlation between vigorous physical activity and the development of left ventricular systolic dysfunction (LVSD), defined as left ventricular ejection fraction below 45% (LVEF <45%), was explored. Additionally, secondary endpoints included the occurrence of life-threatening ventricular arrhythmias (LTA - i.e., aborted cardiac arrest due to hyperkinetic arrhythmias, documented sustained ventricular tachycardia – SVT –, or appropriate implantable cardioverter-defibrillator therapy), non-LTA ventricular arrhythmias (i.e., >1000 premature ventricular complexes/24h and/or non-sustained ventricular tachycardia – NSVT), and the development of atrial fibrillation and/or atrial flutter (AF/AFL) during follow-up.

Results

Among the 117 subjects (73% male, median age 45 – IQR 35-57 years), 38 (32%) were Athletes. Vigorous exercise was not associated with the development of LVEF <45% (adjusted OR 0.663, 95%CI 0.261-1.685, p 0.388), nor with the occurrence of LTA (p = 0.607), non-LTA (p = 0.648), and supraventricular arrhythmias (p = 0.701). Comparable results were obtained when considering the total amount of METs x hours/life burned by subjects as a continuous variable.

Conclusion

In carriers of TTNtv, vigorous physical activity was not associated with LVSD and LTA development.
Temporal fruit microbiome and immunity dynamics in post-harvest apple (Malus x domestica)
Authors: Kithan-Lundquist Roselane , McMillan Hannah M , He Sheng-Yang , Sundin George W
Published: February 2025

The plant immune response plays a central role in maintaining a well-balanced and healthy microbiome for plant health. However, insights on how the fruit immune response and the fruit microbiome influence fruit health after harvest are limited. We investigated the temporal dynamics of the fruit microbiota and host defense gene expression patterns during post-harvest storage of apple fruits at room temperature. Our results demonstrate a temporal dynamic shift in both bacterial and fungal community composition during post-harvest storage that coincides with a steep-decline in host defense response gene expression associated with pattern-triggered immunity. We observed the gradual appearance of putative pathogenic/spoilage microbes belonging to genera Alternaria (fungi) and Gluconobacter and Acetobacter (bacteria) at the expense of Sporobolomyces and other genera, which have been suggested to be beneficial for plant hosts. Moreover, artificial induction of pattern-triggered immunity in apple fruit with the flg22 peptide delayed the onset of fruit rot caused by the fungal pathogen Penicillium expansum. Our results suggest that the fruit immune response helps to orchestrate a microbiome and that the collapse of the immunity results in the proliferation of spoilage microbes and fruit rot. These findings hold implications for the development of strategies to increase fruit quality and prolong shelf life in fruits and vegetables.
Comprehensive waterfront development of Jeddah: a framework for sustainable economic and social impact assessment
Authors: Gbban Abdulrhman Mahmoud , Bahreldin Ibrahim Zakaria , Hegazy Ibrahim Rizk
Published: February 2025

This study assesses the economic and social impacts of the development of the Jeddah Corniche, examining how water infrastructure investments align with Saudi Vision 2030 for sustainable urban growth, economic diversification, and improved quality of life. Applying input–output and cost–benefit analysis frameworks, the study estimates the contributions of desalination and wastewater treatment projects to GDP, job creation, and tourism. The results indicate that these initiatives could boost GDP by approximately 4%, create 15 000 jobs, and increase tourism revenues by 20% over 5 years. These insights are used to formulate policy recommendations to improve the sustainability of urban development in Jeddah.
Rapid clonal expansion and somatic hypermutation contribute to the fate of SARS-CoV-2 broadly neutralizing antibodies
Authors: Wang Miao , Liu Congcong , Fan Qing , Sun Yuehong , Tang Shilong , Guo Huimin , Zhou Bing , Wang Haiyan , Ge Xiangyang , Zhang Zheng , Ju Bin
Published: February 2025

Several vaccines and immunization strategies, including inactivated vaccines, have proven effective in eliciting antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), providing an opportunity to characterize the antibody response. In this study, we investigated the monoclonal antibody responses elicited by wild-type SARS-CoV-2 inactivated vaccination compared to those elicited by natural infection and mRNA vaccination. The analysis showed that antibodies encoded by biased germline genes were shared between SARS-CoV-2 vaccinated and naturally infected individuals. Among the 35 shared clonotypes identified, besides the well-known IGHV3-53 and IGHV1-58, we identified a class of IGHV4-59 antibodies characterized by rapid response and neutralizing activity, elicited by 3 doses of inactivated vaccine. Members of this lineage exhibited similar sensitivity against wild-type SARS-CoV-2, whereas different neutralizing activities against SARS-CoV-2 variants, especially against various Omicron subvariants, BA.1, BA.2, BA.2.12.1, BA.4/5, and BA.2.75. Structural analysis of BA.1 spike complexed with VacBB-639 revealed that the IGHV4-59-lineage antibodies belonged to the Class 2/3 group. Using sequence alignment, site-mutation assays, and functional verification, we identified two substitutions, N60K in HFR3 and S56G in HCDR2, contributing to opposite neutralization changes of IGHV4-59-lineage antibodies against these Omicron subvariants. These results demonstrate the importance of somatic hypermutation in the evolution of prototypical antigen-elicited antibodies in terms of their neutralization breadth and potency against SARS-CoV-2 Omicron variants.
Practical design considerations for cluster randomized controlled trials: lessons learned in community oncology research
Authors: Dressler Emily V , Pugh Stephanie L , Gunn Heather J , Unger Joseph M , Zahrieh David M , Snavely Anna C
Published: February 2025

Cancer care delivery research trials conducted within the National Cancer Institute (NCI) Community Oncology Research Program (NCORP) routinely implement interventions at the practice or provider level, necessitating the use of cluster randomized controlled trials (cRCTs). The intervention delivery requires cluster-level randomization instead of participant-level, affecting sample size calculation and statistical analyses to incorporate correlation between participants within a practice. Practical challenges exist in the conduct of these cRCTs due to unique trial network infrastructures, including the possibility of unequal participant accrual totals and rates and staggered study initiation by clusters, potentially with differences between randomized arms. Execution of cRCT designs can be complex, ie, if some clusters do not accrue participants, unintended cluster-level crossover occurs, how best to identify appropriate cluster-level stratification, timing of randomization, and multilevel eligibility criteria considerations. This article shares lessons learned with potential mitigation strategies from 3 NCORP cRCTs.
Carbon-based pedicle screw fixation for lumbar fusion for degenerative pathologies in a cancer patient requiring radiotherapy
Authors: Mobbs Ralph Jasper , Liu Daniel
Published: February 2025

Spinal instability due to degenerative pathologies in patients with metastatic cancer presents significant challenges when spinal fusion and post-operative imaging and radiotherapy are required. Traditional metallic hardware hinders imaging quality and radiotherapy precision due to metal artefact. Carbon-fiber-reinforced polymer (CFRP) implants offer a novel solution, combining mechanical stability with radiolucency to enhance post-operative multidisciplinary care. We present the case of a patient with metastatic cancer requiring spinal stabilization and fusion. To address the dual needs of spinal stabilization and radiotherapy planning, CFRP pedicle screws and rods were used. Postoperative imaging and radiotherapy planning benefited from the radiolucent properties of the implants, enabling precise tumor targeting and disease monitoring. This case highlights the advantages of CFRP implants in managing cancer-associated spinal instability. The radiolucent nature of these implants allows for high-quality imaging and optimal radiotherapy delivery, addressing limitations associated with metallic implants.
More than a passive barrier: algal cell walls play an active role in determining cell shape, cell size, and organelle morphology
Authors: Hoffmann Natalie
Published: February 2025

This article comments on:

LoRicco JG, Malone S, Becker A, Xue N, Bagdan K, Eastman A, Sgambettera G, Winegrad A, Gibeau. B, Bauer L, Epstein R, Domozych DS. 2025. Aberrant growth and expansion in Penium margaritaceum triggered by disruption of microtubules and the cell wall. Journal of Experimental Botany75, 961–979. https://doi.org/10.1093/jxb/erae387
High-throughput screening of wheat leaf dark respiration identifies significant genetic control
Authors: Vicente Rubén , Fernie Alisdair R , Uberegui Estefanía
Published: February 2025

This article comments on:

Gaju O, Bloomfield KJ, Negrini ACA, Bowerman AF, Cullerne D, Posch BC, Bryant C, Fan Y, Spence M, Stone B, Gilliham M, Furbank RT, Molero G, Pogson BJ, Mathews K, Millar AH, Pearson AL, Reynolds MP, Stroeher E, Taylor NL, Turnbull MH, Atkin OK. 2025. Accounting for the impact of genotype and environment on variation in leaf respiration of wheat in Mexico and Australia. Journal of Experimental Botany 76, 1099–1115. https://doi.org/10.1093/jxb/erae449.
Root sweet root: how date palm uses osmotic adjustment to thrive in arid climates
Authors: Hernandez-Santana Virginia , Pichaco Javier
Published: February 2025

This article comments on:

Franzisky BL, Mueller HM, Du B, Lux T, White PJ, Carpentier SC, Winkler JB, Schnitzler JP, Kudla J, Kangasjärvi J, Reichelt M, Mithöfer A, Mayer KFX, Rennenberg H, Ache P, Hedrich R, Messerer M, Geilfus CM. 2025. Date palm diverts organic solutes for root osmotic adjustment and protects leaves from oxidative damage in early drought acclimation. Journal of Experimental Botany 76, 1244–1265 https://doi.org/10.1093/jxb/erae456.
Real-world treatment persistence in csDMARD-IR and bDMARD-IR patients with rheumatoid arthritis in Japan: A large claims database study
Authors: Takeuchi Tsutomu , Pfeifer Craig , Zhong Yan , Piao Yi , Kaise Toshihiko , Tani Mahiro
Published: February 2025

Objectives: To investigate treatment persistence for biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKis), including filgotinib, in Japanese patients with rheumatoid arthritis (RA) with inadequate response (IR) to conventional synthetic DMARDs (csDMARD-IR) and bDMARDs (bDMARD-IR) and identify characteristics associated with treatment discontinuation.

Methods: We analyzed 2020–2023 health claims data from adults with RA who received ≥1 prescription for bDMARDs or JAKis during the study period and ≥1 prescription for csDMARDs over 6 previous months. Persistence rates were estimated for the csDMARD-IR (patients naïve to bDMARDs/JAKis switching from csDMARDs to bDMARDs or JAKis) and bDMARD-IR (patients switching to bDMARDs or JAKis from an initial bDMARD) cohorts using the Kaplan-Meier method.

Results: Overall, 7208 and 1581 patients were identified in the csDMARD-IR and bDMARD-IR cohorts, respectively. In the csDMARD-IR cohort, 1-year persistence rates were 59%–70% for JAKis (67% for filgotinib) and 53%–69% for bDMARDs. In the bDMARD-IR cohort, 1-year persistence rates were 57%–66% for JAKis (66% for filgotinib) and 19%–91% for bDMARDs. No clinical characteristics were consistently associated with persistence of JAKi or bDMARD treatment.

Conclusions: Rates of persistence among patients taking JAKis, including filgotinib, were approximately 60% or higher in csDMARD-IR and bDMARD-IR cohorts.
NAIL-MS reveals tRNA and rRNA hypomodification as a consequence of 5-fluorouracil treatment
Authors: Berg Maximilian , Li Chengkang , Kaiser Stefanie
Published: February 2025

Recent studies have investigated RNA modifications in response to stressors like chemical agents, including the anticancer drug 5-fluorouracil (5-FU). Traditionally, 5-FU’s mechanism of action was believed to involve inhibition of thymidylate synthase, leading to thymidine depletion and cancer cell death. However, recent findings suggest that ribosome collisions and defects in ribosomal RNA (rRNA) processing drive 5-FU toxicity, potentially through RNA writer inhibition. To explore the effects of 5-FU on rRNA and transfer RNA (tRNA) modifications, we exposed HEK293T cells to 5-FU and quantified key RNA modifications. We found 55% and 40% reduction in 5-methyluridine and pseudouridine (Ψ), respectively, in tRNAs, but only minor changes in rRNA. Using nucleic acid isotope labeling coupled mass spectrometry (NAIL-MS), we identified that pre-existing tRNA and rRNA retained their modification profiles, while newly synthesized RNAs lost various modifications. In addition, new tRNAs exhibited modification reprogramming, particularly important for cell survival after 5-FU removal. In rRNA, we observed reduced levels of mature rRNA, with hypomodification in newly transcribed mature rRNA, particularly in Ψ and ribose methylations. In summary, we observe RNA hypomodification in both tRNA and rRNA due to 5-FU, which might be the molecular basis of 5-FU’s mechanism of action.
Shiba: a versatile computational method for systematic identification of differential RNA splicing across platforms
Authors: Kubota Naoto , Chen Liang , Zheng Sika
Published: February 2025

Alternative pre-mRNA splicing (AS) is a fundamental regulatory process that generates transcript diversity and cell type variation. We developed Shiba, a comprehensive method that integrates transcript assembly, splicing event identification, read counting, and differential splicing analysis across RNA-seq platforms. Shiba excels in capturing annotated and unannotated AS events with superior accuracy, sensitivity, and reproducibility. It addresses the often-overlooked issue of junction read imbalance, significantly reducing false positives to aid target prioritization and downstream analyses. Unlike other tools that require large numbers of biological replicates or resulting in low sensitivity and high false positives, Shiba's statistics framework is agnostic to sample size, as demonstrated by simulated data and its effective application to real n= 1 RNA-seq datasets. To extend its utility to single-cell RNA-seq, we developed scShiba, which applies Shiba's pseudobulk approach to analyze splicing at the cluster level. scShiba successfully revealed AS regulation in developmental dopaminergic neurons and differences between excitatory and inhibitory neurons. Both Shiba and scShiba are available in Docker/Singularity containers and Snakemake pipelines, ensuring reproducibility. With their comprehensive capabilities, Shiba and scShiba enable systematic quantification of alternative splicing events across various platforms, laying a solid foundation for mechanistic exploration of the functional complexity in RNA splicing.
Protein bL38 facilitates incorporation of uL6 during assembly of the 50S subunit in Flavobacterium johnsoniae
Authors: Alom Md Siddik , Arpin Dominic , Zhu Haojun , Hay Brenna N , Foster Leonard J , Ortega Joaquin , Fredrick Kurt
Published: February 2025

Previous studies of the 70S ribosome from Flavobacterium johnsoniae revealed a novel ribosomal protein, bL38, which interacts with uL6 on the 50S subunit. This 5.6 kDa protein is conserved across the Bacteroidia and encoded downstream of bL28 and bL33 in a three-gene operon. Here, we show that bL38 is critical for the growth of F. johnsoniae, and depletion of bL38 leads to accumulation of immature 50S particles, which lack uL6 and retain precursor rRNA sequences. Cryo-EM analysis of these particles reveals several putative assembly intermediates, all showing an absence of electron density for uL6 and the entire uL12 stalk region and additional densities corresponding to the unprocessed ends of the pre-23S rRNA. Extra copies of the uL6 gene can rescue the phenotypes caused by bL38 depletion, suggesting that bL38 facilitates uL6 incorporation during 50S subunit biogenesis. Cryo-EM analysis of 50S particles from this rescued strain reveals nearly twice as many intermediates, suggesting a broader and more robust assembly landscape. Differential scanning fluorimetry shows that uL6 of F. johnsoniae is intrinsically unstable, and bL38 increases the melting temperature of uL6 by 12°C. Collectively, these data suggest that bL38 binds and stabilizes uL6, thereby promoting 50S biogenesis in the Bacteroidia.
The IGF2BP1 oncogene is a druggable m6A-dependent enhancer of YAP1-driven gene expression in ovarian cancer
Authors: Schott Annekatrin , Simon Theresa , Müller Simon , Rausch Alexander , Busch Bianca , Glaß Markus , Misiak Danny , Dipto Mohammad , Elrewany Hend , Peters Lara Meret , Tripathee Sunita , Ghazy Ehab , Müller Florian , Rolnik Robin Benedikt , Lederer Marcell , Hmedat Ali , Vetter Martina , Wallwiener Markus , Sippl Wolfgang , Hüttelmaier Stefan , Bley Nadine
Published: February 2025

The Hippo/YAP1 signaling pathway regulates normal development by controlling contact inhibition of growth. In cancer, YAP1 activation is often dysregulated, leading to excessive tumor growth and metastasis. SRC kinase can cross talk to Hippo signaling by disrupting adherens junctions, repressing the Hippo cascade, or activating YAP1 to promote proliferation. Here, we demonstrate that the IGF2 messenger RNA-binding protein 1 (IGF2BP1) impedes the repression of YAP1 by Hippo signaling in carcinomas. IGF2BP1 stabilizes the YAP1 messenger RNA (mRNA) and enhances YAP1 protein synthesis through an m6A-dependent interaction with the 3′ untranslated region of the YAP1 mRNA, thereby increasing YAP1/TAZ-driven transcription to bypass contact inhibition of tumor cell growth. Inhibiting IGF2BP1–mRNA binding using BTYNB reduces YAP1 levels and transcriptional activity, leading to significant growth inhibition in carcinoma cells and ovarian cancer organoids. In contrast, SRC inhibition with Saracatinib fails to inhibit YAP1/TAZ-driven transcription and cell growth in general. This is particularly significant in de-differentiated, rather mesenchymal carcinoma-derived cells, which exhibit high IGF2BP1 and YAP1 expression, rendering them less reliant on SRC-directed growth stimulation. In such invasive carcinoma models, the combined inhibition of SRC, IGF2BP1, and YAP1/TAZ proved superior over monotherapies. These findings highlight the therapeutic potential of targeting IGF2BP1, a key regulator of oncogenic transcription networks.
Comprehensive analysis of RNA–chromatin, RNA–, and DNA–protein interactions
Authors: Khlebnikov Daniil A , Nikolskaya Arina I , Zharikova Anastasia A , Mironov Andrey A
Published: February 2025

RNA–chromatin interactome data are considered to be one of the noisiest types of data in biology. This is due to protein-coding RNA contacts and nonspecific interactions between RNA and chromatin caused by protocol specifics. Therefore, finding regulatory interactions between certain transcripts and genome loci requires a wide range of filtering techniques to obtain significant results. Using data on pairwise interactions between these molecules, we propose a concept of triad interaction involving RNA, protein, and a DNA locus. The constructed triads show significantly less noise contacts and are more significant when compared to a background model for generating pairwise interactions. RNA–chromatin contacts data can be used to validate the proposed triad object as positive (Red-ChIP experiment) or negative (RADICL-seq NPM) controls. Our approach also filters RNA–chromatin contacts in chromatin regions associated with protein functions based on ChromHMM annotation.
The enduring effects of early life adversity on the dysregulation of the stress awakening response among dependent tobacco users
Authors: Anker Justin J , Nakajima Motohiro , Hatsukami Dorothy , Allen Sharon S , al’Absi Mustafa
Published: February 2025

Introduction

Adults with early life adversity (ELA) often exhibit stress system dysregulation and are prone to smoke for stress relief. This study, conducted as part of a larger project examining psychobiological stress responses in smokers, specifically focuses on the a priori research question of how ELA influences the cortisol awakening response (CAR) during acute tobacco withdrawal.

Methods

Using quasi-experimental design, adult daily (heavy) smokers were randomly assigned to either regular smoking (ad-lib) (N=37) or 24-hour withdrawal (N=55), and categorized into low or high ELA. CO levels verified smoking status, and CAR was assessed through salivary cortisol upon awakening and at 30 and 60 post-wakening. CAR was evaluated using mean cortisol levels, peak reactivity, and area under the curve with respect to increase (AUCi) and ground (AUCg) while controlling for possible covariates. Self-reported measures of mood, craving, and withdrawal were also analyzed.

Results

Smoking status X ELA interaction on peak cortisol and AUCi. High ELA ad-lib smokers (vs. high ELA withdrawal) had elevated peak and AUCi levels and were higher than low ELA ad-lib smokers with respect to peak (ps < 0.05). Withdrawal (vs. ad-lib smokers) had lower positive affect and higher negative affect, craving, and withdrawal (ps < 0.05). Adult smokers with a history of ELA exhibit heightened stress response dysregulation, as evidenced by altered CAR, compared to those without ELA or in smoking withdrawal.

Conclusions

These findings demonstrate that early life adversity significantly exacerbates stress system dysregulation among adult smokers, as evidenced by alterations in the cortisol awakening response. Identifying ELA experiences in smokers may inform the development of more targeted interventions for stress management and tobacco cessation.

Implications

Findings from this study suggest ELA not only leads to an earlier initiation of smoking but also worsens stress system dysregulation in adult smokers. These insights highlight the importance of developing early prevention strategies aimed at adolescents with ELA to prevent smoking initiation and reduce its impact on stress regulation. Additionally, the findings support the need for customized, trauma-informed smoking cessation programs for adults with ELA, emphasizing the necessity to address the distinct challenges related to stress regulation and nicotine withdrawal they face.
Climatic Variability and Associated Changes in a Nigerian Nature Forest Reserve
Authors: Olanipon Damilola Grace , Adewoyin Adelowo Adefisayo , Eludoyin Adebayo Oluwole
Published: February 2025

Climate variability and its impact have become of serious interest to environmentalists worldwide, but reports from many sub-Saharan African countries are still relatively more uncertain than many parts, mostly due to challenges with datasets and methodology. In this study, the daily rainfall and temperature records for 34 years (1984–2018; for which data were available at the time of study) were examined alongside changes in the land cover at a natural forest reserve in the Ife area of southwestern Nigeria. The specific objective was to examine climate variability with changes in the land cover of the nature reserve. Data used included archival records of rainfall and temperature and open-access Landsat satellite imageries of the area. Results showed that area experienced rainfall fluctuations, significant monthly decrease and temperature rise in many months increase. The Normalized Difference Vegetation Index and supervised classification of land cover also revealed a decline in vegetation health and loss of forested land to non-forest uses such as farmlands and built-up lands over time. The study could not establish a direct link between forest loss and climate change in the study area but detected a complex implication of urban pressure through human activities and urbanization, and thus concluded that the impact of climate change on the forest environment has been exacerbated by pressure for urban growth and probably a poorly monitored quest for land resource.
Overstatement of GDP growth in autocracies and the recent decline in global inequality
Authors: Pandian Roshan K
Published: February 2025

After rising for almost two centuries, global income inequality declined substantially after 2000. While past scholarship on global inequality has explored several causes for this recent decline in inequality, these studies take for granted the official GDP figures released by national governments. A parallel social science literature has documented the manipulation of official data to exaggerate economic performance in autocratic countries, but this work has stopped short of examining the broader implications of this phenomenon. In this study, I explore the overstatement of GDP growth figures in autocracies as another contributor to the recent decline in estimates of global inequality based on officially reported GDP figures. Drawing on satellite-based night-time lights data and an empirical strategy from recent research, I compute model-based estimates of GDP overstatement in autocracies. I then combine this information with data on within-country income inequality to arrive at adjusted estimates of global income inequality in a sample of 109 countries constituting 92 percent of the world’s population. I find that between 1995 and 2014, ~20 percent of the decline in global inequality can be explained by the overstatement of GDP growth in less democratic countries. I conclude by discussing the broader implications of these findings for our understanding of global inequality and its political economy.
Amoxicillin-induced linear IgA bullous dermatosis mimicking erythema multiforme: a case report
Authors: Silagy Marion , Carvalho Priscille , Tedbirt Billal , Tamarit Clémence , Carrette Marion , Tétart Florence , Lefebvre Alexis
Published: February 2025

A 77-year-old man presented with a cutaneous rash of 3 days. Seven days before the onset, the patient reported a bronchopulmonary infection treated with amoxicillin. Physical examination revealed multiforme cutaneous lesions, involving the armpits, pubis, genitals, and lower back. In the lower back area, lesions were erythematous, purplish targetoid-like with multiple concentric circles. In places, bullae and post-blistering erosions could be seen. In places, a ‘string of pearls’ pattern could be observed. The Nikolsky sign was negative. Herpes simplex virus polymerase chain reaction (PCR) on mucosal erosions was negative. Multiplex nasopharyngeal PCR was negative for influenza virus, COVID-19, and mycoplasma pneumoniae. Histopathological examination revealed spontaneous subepithelial cleavage with neutrophilic micro-abscesses. Direct immunofluorescence showed linear immunoglobulin A (IgA) deposit on the dermal–epidermal junction affirming the diagnosis of linear IgA bullous dermatosis. As for therapeutic management, skin lesions were treated with topical clobetasol propionate cream and oral mucosa with corticosteroid mouth rinses. The disease course was marked by complete remission 7 days after amoxicillin discontinuation. There was no relapse after 4 months of follow-up.
Blue Light Influences Negative Thoughts of Self
Authors: Burge Malisa T , Lumapas Ronel A , Lander Alicia C , Thomas Brianna G , Phillips Andrew J K , Cain Sean W
Published: February 2025

Darkness is equated with sadness. This study explored how light that differentially impacts non-visual photoreception (blue-enriched vs blue-depleted light) affects how we feel about ourselves. In a repeated-measured design, thirty-five participants (22 female participants, 13 male participants, Mage = 20.29, SD = 2.09) completed the Self-Referential Encoding Task (SRET) under both blue-enriched or blue-depleted light conditions, with light conditions randomised and counterbalanced between sessions. The SRET involved participants deciding whether positive (e.g., “good”) and negative (e.g., “terrible”) words were self-descriptive. Trial-by-trial performance analysis using logistic mixed effects models revealed that blue-enriched light significantly increased the likelihood of rejecting negative words as self-descriptive. A Hierarchical Drift Diffusion Model (HDDM) further examined latent decision-making processes and found evidence accumulation to be faster under blue-enriched light when rejecting negative descriptors, suggesting rejecting negative self-descriptors was easier under blue-enriched light. We find light can acutely influence self-perception, with blue-enriched light decreasing negative self-thoughts.
The effect and mechanism of atorvastatin regulating PI3K-Akt–mTOR pathway on radiosensitivity of hepatocellular carcinoma cells
Authors: Deng Zhengzheng , Guo Jinjing , Zhu Zihao , Qing Qiancheng , Wan Dangting , Lei Pengyuan , Liu Qi , Huang Bo
Published: February 2025

Radiation therapy is an important method to treat liver cancer, but because of the strong DNA repair ability of liver cancer cells, even after receiving high doses of radiation still can not get satisfactory results. Atorvastatin (ATO) is a lipophilic and tissue-selective inhibitor of HMG-CoA reductase whose anticancer effects have been validated in various cells, but its effect on the radiation sensitivity of hepatocellular carcinoma cells remains unclear. Therefore, Therefore, this study explored the radiosensitivity of ATO and its possible mechanism by pretreating HepG2 with ATO and collecting HepG2 cells after irradiation. It was found that atorvastatin can not only affect the survival of liver cancer cells when used alone, but also enhance the radiation sensitivity of HepG2 cells. The study found that ATO significantly exacerbated the inhibitory effects of IR on the growth, proliferation, and migration of HepG2 cells. Measurement of ROS, SOD, GPx, and MDA levels indicated that ATO enhanced IR-induced oxidative stress, further promoted the decrease of Mitochondrial Membrane Potential, increased the rate of apoptosis in HepG2, upregulating pro-apoptotic proteins Bax and Cleaved-Caspase 3, and downregulating anti-apoptotic proteins Bcl-2. Western blot analysis showed that the PI3K-Akt–mTOR pathway was inhibited, leading to the activation of cytotoxic autophagy in HepG2 and an increase in the expression of the LC-3II protein. In summary, ATO, in combination with IR, enhances the oxidative stress response of HepG2 induced by IR, promotes autophagy by inhibiting the PI3K-Akt–mTOR pathway, and thereby potentially enhances the radiosensitivity of HepG2 as a pharmacological intervention.
Evaluation of Fungicides for Control of Vascular Streak Dieback on Field Grown Eastern Redbud in McMinnville, TN, 2023
Authors: Baysal-Gurel Fulya , Liyanapathiranage Prabha , Simmons Terri , Oksel Cansu , Hikkaduwa Epa Liyanage Kumuditha , Dawadi Sujan
Published: February 2025

Vascular streak dieback (VSD) in redbud is a growing issue causing significant losses for nursery growers in the United States. Causal agent of VSD is not yet confirmed, but Ceratobasidium sp. has been frequently isolated from plants exhibiting VSD symptoms, including vascular streaking, stunted growth, leaf scorch, defoliation, top dieback and death. In 2023, a field trial in McMinnville, TN, assessed fungicide effectiveness against VSD in one-year-old Eastern redbud plants. The plants were monitored for VSD symptoms throughout the growing season. The findings will aid in developing management strategies aimed at controlling VSD and minimizing its economic impact.
Choosing a drug to treat motion sickness
Authors: Bodner Gayle B. , Perry Courtney J.
Published: February 2025

Patients who suffer from motion sickness despite avoiding triggers and using behavioral modifications may benefit from individualized recommendations for pharmacologic therapy. Patients with refractory motion sickness can benefit from prophylactic drug therapy using first-generation antihistamines or scopolamine.
Evaluating the Association Between Physical Therapy Variables and Outcomes After Lumbar Fusion
Authors: Heard Jeremy C. , Ezeonu Teeto , Lee Yunsoo , Narayanan Rajkishen , Kellish Alec , Dulitzki Yoni , Resnick Dylan , Zucker Jeffrey , Shaer Alexander , Canseco Jose A. , Rihn Jeffrey A. , Woods Barrett , Hilibrand Alan S. , Vaccaro Alexander R. , Kepler Christopher K. , Schroeder Gregory D.
Published: February 2025

Study Design:

Retrospective cohort study.

Objective:

The purpose of this study was to investigate how inpatient physical therapy variables impact (1) inpatient complications, (2) 90-day readmissions, (3) 1-year reoperation rates, and (4) length of stay after posterior lumbar decompression and fusion.

Summary of Background Data:

Previous studies have emphasized the role of early ambulation in postoperative spine patients as an effective method for improving pain and decreasing length of stay, but few studies have evaluated the efficacy of inpatient physical therapy.

Methods:

Patients 18 years of age or older who underwent primary 1-level or 2-level posterior lumbar decompression and fusion from 2019 to 2020 were retrospectively identified. Physical therapy data, including time to first inpatient PT session, gait trial distance achieved, post-treatment pain rating, and Activity Measure for Post-Acute Care (Activity Measure for Post-Acute Care [AM-PAC]) scores were collected using manual chart review. Surgical outcome variables included length of stay, inpatient complications, 90-day readmissions, and reoperations within 1 year of primary surgery.

Results:

Overall, 425 patients were identified. There was no difference in hours to PT or total gait trial distance achieved between patients who experienced a complication and those that did not. Patients in the noncomplication group had higher AM-PAC scores than patients in the complication group. There was no difference with regards to time to PT, AM-PAC score, or gait trial distance achieved between readmitted patients and nonreadmitted patients or revision patients and nonrevision patients. Stepwise logistic regression showed that having a physical therapy session within 6 hours of surgery was predictive of a decreased length of stay both in all patients.

Conclusions:

While inpatient physical therapy within 6 hours of surgery does not appear to impact readmissions, complications, or reoperations, surgeons should encourage early ambulation postoperatively to decrease extended hospital stays. Future investigation should seek to identify factors that delay inpatient PT in the 6 hours after surgery.
The Free Distal Clavicle Osteochondral Flap: Cadaveric Dissection and Case Report to Introduce a Novel Technique
Authors: Van Kouwenberg Emily , Sacks Brittany L. , Gluck Matthew J. , Bernstein Zachary L. , Zhang Yiyang , Onuh Ogechukwu , Hausman Michael R.
Published: February 2025

Vascularized osteochondral flap reconstruction is an innovation with several potential benefits, but there are limited described autologous donor site options. This study explores the distal clavicle as a viable donor site for vascularized free osteochondral tissue transfer. Cadaveric dissection was performed in which a 39-year-old male with a comminuted fracture of the right distal humerus underwent open reduction and internal fixation. The patient later presented with avascular necrosis of the lateral column of the distal humerus and right trochlea and underwent reconstruction of the distal humerus with iliac crest bone graft and vascularized free osteochondral transfer of the distal clavicle. The distal clavicle was harvested with its periosteum and a small muscle cuff based on the acromial branch of the thoracoacromial system. The authors report a novel technique for distal clavicle osteochondral flap harvest and present a case in which the technique was used successfully in complex elbow reconstruction.
Navigating Pregnancy in Congenital Heart Disease: A Comprehensive Review of Maternal Outcomes
Authors: Ahmad Rimsha , Frishman William H. , Aronow Wilbert S.
Published: February 2025

Congenital heart disease (CHD) affects approximately 0.5–1% of the population, with advancements in cardiovascular care enabling 97% of these individuals to survive to adulthood. Pregnancy in women with CHD presents with unique challenges due to increased hemodynamic demands and associated risks. This review provides a comprehensive analysis of maternal outcomes in women with CHD, focusing on the physiological changes during pregnancy, classification of CHD types, and their specific consequences. The review highlights significant complications within this population, such as arrhythmias, heart failure, thromboembolic events, and aortic dissection, emphasizing the need for multidisciplinary management and individualized care. Despite considerable advancements, gaps in research persist, particularly in neonatal risk prediction and long-term maternal outcomes. Future directions prioritize the refinement of risk stratification models and leveraging emerging technologies to enhance care for this complex population.
The Effect of Age on Antipsychotic Serum Concentration in Males and Females: A Study Based on Therapeutic Drug Monitoring Data From 19,926 Patients
Authors: Solhaug Vigdis , Waade Ragnhild Birkeland , Molden Espen , Størset Elisabet , Høiseth Gudrun , Tveito Marit
Published: February 2025

Background:

Antipsychotic medications are commonly prescribed for older patients; however, documentation on their safety and efficacy in this population is limited. This study aimed to investigate and compare the effect of age on dose-adjusted serum concentrations of 6 commonly used antipsychotic medications in both sexes.

Methods:

Patients with serum concentration measurements of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, and zuclopenthixol were retrospectively included from a therapeutic drug monitoring service. The primary outcome measure for each antipsychotic was the dose-adjusted serum concentration (C:D ratio), assessed across groups divided by sex and age (18–49 years, 50–74 years, and ≥75 years). The data were analyzed using linear mixed modeling with restricted maximum likelihood estimation.

Results:

A total of 19,926 patients (53% male) with 74,194 serum concentration measurements were included. For most antipsychotics, the C:D ratios increased significantly with age, with generally larger differences observed in females compared with males. The largest impact of age was observed for risperidone, where C:D ratios in the age groups 50–74 years and ≥75 years were 20% and 81% higher for males, respectively, compared with the reference group (18–49 years). For females, the C:D ratios were 28% and 92% higher, respectively, compared with females aged 18–49 years (all P < 0.001). The smallest impact of age was observed for aripiprazole, with no significant differences in C:D ratios across age groups for males. For females treated with aripiprazole, C:D ratios were 8% and 28% higher in the 50–74 and ≥75 years age groups, respectively, compared with females aged 18–49 years (both P < 0.001).

Conclusions:

The age-dependent increase in dose-adjusted serum concentrations among males and females varied across different antipsychotics and was highest for risperidone. These findings emphasize the importance of proper monitoring of antipsychotic use in older adults.
Bridging the Gap: Advancing Pharmacogenetic Testing Through Comprehensive Implementation and Evaluation Strategies
Authors: Rogers Sara , Silva Patrick J. , Ramos Kenneth
Published: February 2025

Pharmacogenomics (PGx) enhances drug therapy by tailoring treatment to individual genetic profiles, thereby improving safety and efficacy. However, the integration of PGx into clinical practice, particularly in hospitals, faces significant challenges, including limited testing services, variant coverage, and inconsistent guidelines. A recent review, “Implementation and Evaluation Strategies of Pharmacogenetic Testing in Hospital Settings,” highlights these challenges and current strategies. Sustaining PGx programs requires ongoing education, support, the integration of advanced technologies, and financial sustainability. Addressing inconsistent insurance coverage, developing standardized methodologies, and implementing clear policies are crucial for widespread adoption, advancement of personalized medicine, and improvement of patient care in hospital settings.
Olanzapine; Postinjection Syndrome; Pharmacokinetics in View: Grand Round/A Case Study
Authors: Rozema Johanne , van Stee Cornelis Paul , Touw Daniel J. , van Meurs Matijs
Published: February 2025

Olanzapine is a second-generation antipsychotic that is frequently administered intramuscularly as a slow-release depot and maintenance treatment for schizophrenia. Therapeutic values range from 20 to 80 mcg/L and levels >100 mcg/L are considered toxic. Postinjection delirium/sedation syndrome (PDSS) is a rare but serious adverse effect after the injection of olanzapine depot formulations. The authors present a case study in which a 64-year-old patient presented to the emergency room 30 minutes after an intramuscular injection of olanzapine with signs of possible postinjection syndrome. The patient presented with hypertension, tachycardia, delirium, and was suspected to have PDSS. On admission, his serum olanzapine levels had reached 390 mcg/L, and blood samples were collected on days 0, 1, 3, and 12. The timing of his presentation at the emergency room made it possible to track the pharmacokinetics of olanzapine in detail. On the basis of Therapeutic drug monitoring, a prolonged olanzapine half-life of 7 days was calculated. Symptoms such as agitation and hypertension improved after approximately 39 hours, and the patient had made a full recovery after 72 hours. This case study can serve as a reference for healthcare providers that will aid in the recognition and treatment of PDSS and contribute to a better understanding of the clinical problems associated with PDSS. In addition, it emphasizes how Therapeutic drug monitoring may be of added value with respect to determining when medication can be safely resumed.
Evaluation of Lateral Triangular Flaps When Combined With Bilateral Superficial Epigastric Artery Flap for Shaft-only Penile Reconstruction
Authors: Mohamed Ashraf El Eebaie , Hafez Hamza Ahmed Abdelsalam , Hussein Mohammed Ahmed
Published: February 2025

Background:

Phalloplasty represents a challenging complex genital reconstruction surgery. Phalloplasty should result in an aesthetic composite phallus, with the ability to void while standing, allowing placement of an implantable prostheses and preserving both tactile and erogenous sensation with minimal donor site morbidity.

Methods:

A bilateral superficial epigastric artery flap was design in the supra pubic area, extending upward till the lower boarder of the umbilicus. Two triangular flaps were designed at the base of the main rectangular flap to facilitate further mobilization of the neophallus. A penile prosthesis was implanted at the same stage in some patients. Finally, the lateral abdominal flaps were dissected and mobilized to be closed primarily in the mid line.

Results:

Twenty patients who were candidate for first stage of penile reconstruction were included in our study. The average flap dimensions were 18 × 15 cm; the largest was 32 × 18 cm, whereas the smallest flap was 15 × 113 cm. Eleven patients had immediate implantation with 2 failures due to impaired sensation. Four patients had tissue expansion before flap harvesting. Three patients developed partial flap loss during the first 2 weeks postoperatively.

Conclusions:

The modified bilateral superficial epigastric artery flap is a convenient flap for neophallus reconstruction. Flap design and harvesting is simple with a minimal learning curve. The flap has good color match with well-hidden donor site morbidity. Also, the bilateral triangular flaps permit adequate caudal repositioning of the neophallus, which gives a more natural position.
Omsk hemorrhagic fever virus: review of the biology, ecology, and disease associated with a historic tick-borne pathogen
Authors: Kumar Nidhi P. , Hathaway Matthew , Demshuk Matthew K. , DeHaven Taylor O. , Farha Stefania M. , Donovan Angelena M. , Burdette Andrew J. , Walls Gracie L. , Selesky Kara M. , Beachboard Dia C. , Stobart Christopher C.
Published: February 2025

Omsk hemorrhagic fever virus (OHFV) is a tick-borne flavivirus associated with acute febrile illness and hemorrhagic disease in humans. OHFV was first identified in 1947 and since its identification has largely remained endemic to the Omsk region of the Russian Federation, where it continues to result in illnesses each year. However, the 2 primary tick vectors of OHFV exhibit ranges that extend far beyond the Omsk region, and the recent positive confirmation of OHFV in samples outside of the historic endemic range, in both the Russian Federation and neighboring Kazakhstan, to the south raises new concerns about the future potential of the pathogen. In this review, we comprehensively discuss the emergence, virology, ecology, and disease of OHFV.
Advertised Australian Early Childhood Intervention Role Descriptions
Authors: Carlon Sarah , Zanuttini Jessica Zoe , Kemp Coral , Gavidia-Payne Susana
Published: February 2025

National best practice guidelines for early childhood intervention (ECI) were first published in Australia in 2016, but research into the implementation of these guidelines has been limited. The purpose of this study was to determine the extent to which the role descriptions of ECI positions advertised by Australian employers aligned with the best practice guidelines. Through secondary analysis of 246 online job advertisements for ECI positions, collected over a 5-month period, we examined role descriptions to identify those including descriptions of key best practices. We also examined the extent to which the skills, knowledge, and experience advertised as essential aligned with best practice role descriptions, and what qualifications were required for best practice roles. Over 97% of the advertised roles included components of one or more of the Australian key best practices, but practices related to family and inclusion were included in less than half of these. Few employers advertising best practice-aligned roles required successful candidates to have knowledge, skills, or experience in the corresponding area. Implications of these findings for both research and practice are presented.