bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative chloroplast genome analysis reveals powerful barcodes for combatting illegal logging of CITES-listed threatened Asian rosewoods (Dalbergia, Leguminosae, Papilionoideae)
Authors: Rather Shabir A , Wang Kaikai , Wang Ting , Liu Hongmei , Schneider Harald
Published: December 2024

Rosewoods (Dalbergia) are among the most heavily trafficked natural resources in the illegal global multibillion-dollar wildlife trade. Consequently, many rosewood species experience high extinction threats. To enforce the conservation of rosewood species threatened by illegal logging, reliable identification is required to distinguish between legally and illegally traded rosewood timber. DNA barcoding is considered the most promising approach to achieve rapid and reliable species identification, compared to morphological and biochemical compound analyses. This study was designed to establish a DNA barcoding approach for rosewoods by utilizing whole-chloroplast genome sequences, either as super-barcodes or as sources to identify short but highly informative DNA barcoding regions. To achieve these objectives, 81 rosewood plastomes that cover 28 species were generated de novo. The phylogenomic dataset was further expanded to include a total of 110 accessions representing 31 species of Dalbergia. The chloroplast genome structure and composition were found to be highly conserved across all the species studied. The phylogenetic hypothesis obtained using the coding sequences data were fully resolved and robust, even for closely related species. Five loci were identified as powerful DNA barcodes that corresponded to sequence variation hotspots. In summary, the whole chloroplast genomes were found to be highly powerful super-barcodes, while up to five plastome loci were identified as small barcode regions that can be amplified even for degraded DNA. This study successfully establishes the resources necessary to carry out DNA barcoding for rosewoods, serving as a main tool to provide reliable identification of threatened species traded in the illegal timber market.
The role of neutrophils in allergic disease
Authors: Trayer James , Isaza-Correa Johana , Kelly Lynne , Kelleher Maeve , Hourihane Jonathan , Byrne Aideen , Molloy Eleanor
Published: December 2024

Neutrophils are short-lived cells of the innate immune system and represent 50–70% of the circulating leucocytes. Their primary role is antimicrobial defence which they accomplish through rapid migration to sites of inflammation followed by phagocytosis, degranulation, and the release of neutrophil extracellular traps (NETosis). While previously considered terminally differentiated cells, they have been shown to have great adaptability and to play a role in conditions ranging from cancer to autoimmunity. This review focuses on their role in allergic disease. In particular: their role as potential amplifiers of type 1 hypersensitivity reactions leading to anaphylaxis; their involvement in alternative pathways of food and drug allergy; their role in allergic rhinitis and asthma and neutrophil dysfunction in atopic dermatitis. The use of potential biomarkers and therapeutic targets is also discussed with a view to guiding future research.
One-pot preparation of micrometer-sized monodispersed silicone hollow particles
Authors: Nishi Hyota , Ishidate Shintaro , Nakamoto Reina , Katsube Shinya , Suzuki Nozomu , Suzuki Toyoko , Minami Hideto
Published: December 2024

Micrometer-sized, monodispersed silicone hollow particles are functional materials with properties attributed to both their hollow structure and the silicone composition. However, there are few reports on their preparation. We have successfully prepared these particles by combining an original suspension polymerization technique, the self-assembling phase-separated polymer method, with a molecular diffusion method. The resulting particles exhibit heat resistance owing to the silicone matrix and maintain their hollow structure even after heating to 900 °C.
Functionally important components of the transcription elongation complex involved in Rho-dependent termination
Authors: Khatri Ajay , Sen Ranjan
Published: December 2024

Bacterial transcription terminator, Rho is an RNA (Ribonucleic Acid)-dependent ATPase that terminates transcription. Several structures of pretermination complexes of the Rho-transcription elongation complex (EC) revealed a static picture of components of the EC that come close to the nascent RNA-bound Rho, where many of the residues of EC reside ≤10 Å from the Rho residues. However, the in vitro-formed Rho-EC complexes do not reveal the in vivo Rho-EC dynamic interaction patterns during the termination process. Here we report synthetic defect analyses of various combinations of the mutations in RNAP β, β’ and ω-subunits, NusA, NusG, and Rho proteins to delineate the functional network of this process. Several mutations in the β-flap and β’-Zn-finger and -Clamp helices domains of RNAP are synthetically defective in the presence of Rho mutants indicating functional involvement of these domains. Mutations in the NusA RNA-binding domains were synthetically defective with the Rho mutants suggesting its involvement. Our genetic analyses also revealed functional antagonisms between the ω-subunit of RNAP and the NusG-CTD (c-terminal domain) during termination. We concluded that the regions surrounding the RNA exit channel, the RNA-binding domains of NusA, the RNAP ω-subunit, and NusG-CTD constitute a functional network with Rho just before the onset of in vivo Rho-dependent termination.
Is there any role for an atrial septal defect in off-loading a borderline left ventricle?
Authors: Hosseinpour Amir-Reza , González-Calle Antonio , Stümper Oliver , Barron David J
Published: December 2024

A small atrial septal defect with right-to-left shunt is useful for off-loading a dysfunctional right ventricle postoperatively. However, an atrial septal defect with left-to-right shunt may not be as useful for a dysfunctional left ventricle. Experimental data are limited at present. Thus, we reconsider the related physiology to guide future approach.
Peer coaching in cardiac surgery: a pilot study on rehabilitation participation and perioperative challenges
Authors: Parhar Kanwar , Holm Aaron , Hira Ravi S , Oyetunji Lara , Collins-Brandon Jeannie , Lehr Eric J , Speck Sarah
Published: December 2024

Following cardiac surgery, active participation in cardiac rehabilitation (CR) is associated with reduced cardiovascular events and improved survival. However, CR attendance remains persistently low, with only ∼25% of patients participating. The Peer Coaching for Cardiac Patients (PCCP) pilot programme aimed to assess whether peer coaching could enhance CR participation and reduce perioperative anxiety and depression in cardiac surgery patients. Ten patients scheduled for elective cardiac surgery were enrolled, receiving 4 60-min coaching sessions via Zoom, by a coach who had undergone coronary artery bypass grafting in the past. Outcomes were measured by CR participation rates, Patient Health Questionnaire (PHQ)-9 scores, and a post-programme survey. Seven of the 10 patients completed the PCCP programme, all of which attended CR for an average of 19.3 ± 8.70 sessions and 9.57 ± 3.0 weeks. No statistically significant difference in PHQ-9 scores was observed (P = 0.341). Participants rated the programme highly in its role in anxiety reduction (9.0 ± 1.2) and likelihood of participating in CR (9.43 ± 1.05). These results suggests that peer coaching shows potential to support CR participation and address perioperative anxiety and depression. Future studies with larger sample sizes, well-defined control groups and extended follow-up are warranted to validate these preliminary findings.
Theta Functions and Projective Structures
Authors: Biswas Indranil , Ghigi Alessandro , Vai Luca
Published: December 2024

Given a compact Riemann surface $X$, we consider the line, in the space of holomorphic sections of $2\Theta $ on $J^{0}(X)$, orthogonal to all the sections that vanish at the origin. This line produces a natural meromorphic bidifferential on $X\times X$ with a pole of order two on the diagonal. This bidifferential is extensively investigated. In particular we show that it produces a projective structure on $X$, which is different from the standard ones.
Penetration of linezolid into the pleural cavity in critically ill patients with proven or suspected Gram-positive bacterial infections: a retrospective pharmacokinetic study
Authors: De Antonio-Cuscó Marta , Sorlí Luisa , Muñoz-Bermúdez Rosana , López-Mula Carlos , Parrilla Francisco José , Gracia-Arnillas Maria Pilar , Prim Núria , Campillo Ambrós Núria , Horcajada Juan P , Masclans-Enviz Joan Ramon , Grau Santiago , Luque Sònia
Published: December 2024

Objectives

To describe the pharmacokinetics (PK) of linezolid in plasma and pleural fluid (PF) in critically ill patients with proven or suspected Gram-positive bacterial infections.

Patients and methods

Observational PK study in 14 critically ill patients treated with linezolid at standard doses. Blood and PF samples were collected and analysed by HPLC. The ratio between PF and plasma concentrations was calculated. The PK/pharmacodynamic (PD) target of linezolid in plasma was defined as 100% of the duration of the dosing interval in which concentrations were above the MIC (%100 T > MIC).

Results

The median (5th and 95th percentiles) linezolid concentration values for plasma pre-dose at steady state (Cmin,ss) and at the end of the 1-h infusion at steady state (Cmax,ss) were 1.1 (0.02–28.3) and 13.8 mg/L (2.9–38.1), respectively, and the PF pre-dose concentration (PF0 h) and PF concentration at the end of the 1-h intravenous infusion (PF1 h) were 2.8 (0.1–31.6) and 4.2 mg/L (0.1–45.2), respectively. At both times (pre-dose and post-infusion), a strong positive correlation was observed between PF and plasma linezolid concentrations (Spearman’s rho coefficients = 0.8 and 0.9, with P < 0.001 for both). The defined PK/PD target in plasma was achieved in 8 (57.1%), 4 (28.6%) and 3 (21.4%) patients assuming an MIC of 1, 2 and 4 mg/L, respectively.

Conclusions

Linezolid seems to penetrate well into the PF, with concentrations exceeding those in plasma. However, high inter-individual variability, both in plasma and PF concentrations, was observed. A high proportion of patients did not achieve the PK/PD target in plasma, especially in the presence of high MIC strains.
Price Variability of Eight Common Laboratory Tests across All Licensed Tennessee Hospitals
Authors: Hart Stephanie A , Khan Ayesha , Booth Garrett S , Wiencek Joesph R
Published: December 2024

Background

In 2021, the United States implemented a federal price transparency mandate to help combat price variability across the country. Initial studies conducted within several months of the mandate showed persistent price variability.

Methods

To assess continued price variability for laboratory tests and factors associated with prices across all licensed hospitals in Tennessee approximately 2.5 years since the mandate, hospital websites were queried for gross, cash, and Blue Cross Blue Shield (BCBS) prices for common laboratory tests (n = 8). Hospital ownership and county demographic data including income, region, and population density were also collected.

Results

All tests showed considerable price variability. Gross price was set higher than cash and BCBS prices. For the majority (n = 6) of tests, cash was higher than BCBS price. Maximum to minimum price ratios for each test ranged from 29 to 114 for gross, 57 to 243 for cash, and 25 to 115 for BCBS prices. Gross and cash prices were associated with median household income of the hospital’s county while BCBS prices were not. Overall, prices were associated with hospital county income, for-profit status, and region.

Conclusions

Our study shows continued price variability in Tennessee 2.5 years after the federal price transparency mandate.
New indices to track interoperability among US hospitals
Authors: Strawley Catherine E , Adler-Milstein Julia , Holmgren A Jay , Everson Jordan
Published: December 2024

Objectives

To develop indices of US hospital interoperability to capture the current state and assess progress over time.

Materials and Methods

A Technical Expert Panel (TEP) informed selection of items from the American Hospital Association Health IT Supplement survey, which were aggregated into interoperability concepts (components) and then further combined into indices. Indices were refined through psychometric analysis and additional TEP input. Final indices included a “Core Index” measuring adoption of foundational interoperability capabilities, a “Pathfinder Index” representing adoption of advanced interoperability technologies and auxiliary exchange activities, and a “Friction Index” quantifying barriers. The first 2 indices were scored from 0 (no interoperability) to 100 (full interoperability); the Friction Index was scored 0 (no friction) to 100 (maximum friction). We calculated indices annually from 2021 to 2023, stratifying by hospital characteristics.

Results

Items within components created reliable and meaningful measures, and associations between components within indices followed the TEP’s expectations. Weighted mean scores for the Core (2023), Pathfinder (2022), and Friction (2023) Indices were 61, 57, and 30, respectively. Hospitals with 500+ beds (large), not designated as critical access, in metropolitan areas, and using market leading electronic health records had statistically significant higher mean scores on all indices. Index values also improved modestly over time.

Discussion

Hospitals performed best on the Core Index. Given recent policy and programmatic initiatives, we anticipate continued improvement across all indices.

Conclusion

Ongoing index tracking can inform policy impact evaluations and highlight persistent interoperability disparities across hospitals.
pyBioPortal: a Python package for simplifying cBioPortal data access in cancer research
Authors: Valerio Matteo , Inno Alessandro , Gori Stefania
Published: December 2024

Objectives

In recent years, the rise of big data and artificial intelligence has led to an increasing expansion of databases and web services in biomedical research. cBioPortal is one of the most widely used platforms for accessing cancer genomic and clinical data. The primary objective of this study was to develop a tool that simplifies programmatic interaction with cBioPortal’s web service.

Materials and Methods

We developed the pyBioPortal Python package, which leverages the cBioPortal REST API to access genomic and clinical data. The retrieved data is returned as a Pandas DataFrame, a format widely used for data analysis in Python.

Results

pyBioPortal offers an efficient interface between the user and the cBioPortal database. The data is provided in formats conducive to further analysis and visualization, promoting workflows and improving reproducibility.

Discussion

The development of pyBioPortal addresses the challenge of accessing and processing large volumes of biomedical data. By simplifying the interaction with the cBioPortal API and providing data in Pandas DataFrame format, pyBioPortal allows users to focus more on the analytical aspects rather than data extraction.

Conclusion

This tool facilitates the retrieval of heterogeneous biological and clinical data in a standardized format, making it more accessible for analysis and enhancing the reproducibility of results in cancer informatics. Distributed as an open-source project, pyBioPortal is available to the broader bioinformatics community, promoting collaboration and advancing research in cancer genomics.
GPLD1+ cancer stem cells contribute to chemotherapy resistance and tumour relapse in intestinal cancer
Authors: Mizoo Taisuke , Oka Takeru , Sugahara Osamu , Minato Takafumi , Higa Tsunaki , Nakayama Keiichi I
Published: December 2024

Cancer stem cells (CSCs) play a central role in cancer progression, therapy resistance, and disease recurrence. With the use of a quadruple-mutant mouse intestinal cancer organoid model and single-cell RNA-sequencing analysis, we have now identified glycosylphosphatidylinositol-specific phospholipase D1 (GPLD1), an enzyme that catalyzes the cleavage of glycosylphosphatidylinositol (GPI) anchors of membrane proteins, as a marker of slowly cycling CSCs. Ablation of Gpld1+ cells in combination with 5-fluorouracil treatment greatly attenuated cell viability in and regrowth of the intestinal cancer organoids. In addition, we identified serine protease 8 (PRSS8) as a key substrate of GPLD1 in human colorectal cancer cells. GPLD1 cleaves the GPI anchor of PRSS8 and thereby mediates release of the protease from the plasma membrane, resulting in the activation of Wnt signalling and promotion of the epithelial-mesenchymal transition (EMT) in the cancer cells. Pharmacological inhibition of GPLD1 suppressed Wnt signalling activity and EMT in association with upregulation of the amount of functional PRSS8 at the plasma membrane. Our findings suggest that targeting of GPLD1 in colorectal cancer might contribute to a new therapeutic strategy that is based on suppression of Wnt signalling and EMT-related cancer progression driven by CSCs.
An application on intuitionistic fuzzy weakly 2-absorbing ideals of lattices
Authors: Yazar Salih , Onar Serkan , Özkan E Mehmet
Published: December 2024

In this study, we investigate the notion of an intuitionistic fuzzy prime ideal and intuitionistic fuzzy weakly 2-absorbing ideal of a lattice as an expansion of a notion of a weakly prime ideal. Then, we characterize the concept of intuitionistic fuzzy weakly 2-absorbing ideals and intuitionistic fuzzy weakly primary ideals and give some results. Finally, we suggest the concept of an intuitionistic fuzzy weakly 2-absorbing ideals in a product of lattices.
Patenting measurements
Authors: Müller Martin
Published: December 2024

At the European Patent Office (EPO), an invention can only be patented if it has technical character and solves a technical problem. According to established case law, in line with probably universal agreement, measurement methods have the required technical character. In its decision G1/19, the Enlarged Board of Appeal has confirmed this principle and stated it extends to what are called indirect measurements. This question is gaining increasing attention, following G1/19, as a potential argument to acknowledge a technical contribution made by an otherwise entirely computer-implemented (‘numerical’) invention, and it may be relevant for any method of analysis, testing or diagnosis of technical devices or patients, for instance in the context of digital twins. Against this backdrop, the article investigates what may or may not be considered an (indirect) measurement for the purpose of patentability.
Radioactive contamination of southeast Abai oblast, Kazakhstan, from the Chinese nuclear weapons testing program at Lop Nor: an analytical review
Authors: Lipikhina Alexandra , Harbron Richard , Apsalikov Kazbek , Brait Yuliya , Yessilkanov Gani , Drozdovitch Vladimir , Ostroumova Evgenia
Published: December 2024

Between 1949 and 1962 the Soviet Union performed atmospheric tests of nuclear weapons at the Semipalatinsk nuclear test site (SNTS) in Kazakhstan, resulting in widespread contamination of the surrounding region with radioactive fallout. Settlements in the southeast Abai oblast of Kazakhstan, close to the border with China, are not thought to have received significant fallout from the SNTS. There is, however, evidence that the study area, including Makanchi, Urdzhar and Taskesken villages, was contaminated by atmospheric nuclear tests performed by China at the Lop Nor NTS between 1964 and 1980. We identified the most reliable data indicating contamination from the Lop Nor tests from archive documents. Prompt sampling of soil performed in the area revealed elevated levels of total beta activity in the days and weeks following the Lop Nor tests. The highest activities were recorded following the thermonuclear tests in June 1967 and June 1973. Tooth enamel dosimetry using electron paramagnetic resonance methods suggests residents of the study area have been exposed to excess doses of 50–60 mGy but provides no information on the source and timing of exposure. Currently, evidence of contamination of the study area from nuclear weapons testing at Lop Nor is based on limited radiation measurement data. Therefore, work will continue on the search for archival data on radiological and meteorological monitoring carried out in the study area at the time of the Lop Nor testing campaign.
How I met my mother: Kinning and new beginnings between unaccompanied Afghan minors and voluntary Danish guardians
Authors: Møller Nielsen Lærke , Rytter Mikkel
Published: December 2024

A relatively large part of the asylum seekers that came to Denmark during ‘the long summer of migration’ in 2015 were under the age of eighteen and travelled without adult relatives. The number of unaccompanied minors from Afghanistan was 844 in 2015 and 527 in 2016. As minors, they receive professional help, care and guidance in the asylum process and are placed in special centres for minors. When they are finally granted temporary residency as refugees, they receive a legal guardian, a volunteer Danish citizen who agrees to help the young refugees establish a new life in the municipality they have been assigned to. Inspired by Signe Howell’s work on transnational adoption in Norwegian families, this article discusses the dynamics of kinning processes where unaccompanied minors and their legal guardians over time develop strong emotional ties. The bumbling transformation of the ‘order of law’ into the ‘order of nature’ not only constitutes a new beginning in family relationships but may also promote a future model for sustainable inclusion of refugees in Denmark.
Constrictive pericarditis as first presentation of IgG4-related disease: Pitfalls and pearls
Authors: Kwan Timothy N , Kwan Gemma , Yiannikas John
Published: December 2024

IgG4-related disease (IgG4-RD) is an under-recognised multisystem inflammatory disorder that has several typical manifestations. Cardiac manifestations of IgG4-RD are well documented; however, they do not feature in the definition or diagnosis of IgG4-RD according to a recent consensus statement. The most well-recognised cardiac manifestation of IgG4-RD, pericardial disease, is outlined in this case report as the initial presenting pathology. In the present case, the diagnosis was delayed due to the relative obscurity of cardiac manifestations of IgG4-RD and exposed the patient to the risks of pericardiectomy.
Music Therapy Preferences Among Breast Cancer Patients Undergoing Chemotherapy: A Qualitative Study
Authors: Nakaya Nanami , Yamasato Ami , Kondo Mayu , Okino Shigeki , Kitano Atsuko , Yamamoto Kenji
Published: December 2024

Evidence suggests that music therapy may be effective for patients with cancer. However, its efficacy can be improved by tailoring it to each patient’s needs, disease, and treatment conditions. Since few studies have investigated the music therapy preferences of patients with cancer, this qualitative study aimed to identify such preferences among patients with breast cancer undergoing chemotherapy. For this purpose, individual semi-structured interviews were conducted with 14 adult patients with breast cancer who had received perioperative chemotherapy in Japan. The data were analyzed based on a grounded theory approach, revealing the following categories: (a) relationship to music, (b) pain from treatment, and (c) preferences for music therapy. Based on these results, we were able to determine the specific music therapy preferences of patients with breast cancer undergoing chemotherapy. In addition, we identify patient preferences for music therapy content, time, timing, and fees and discuss the process of meeting these preferences. Identifying these preferences is crucial to providing meaningful interventions to music therapy recipients.
Deciphering ligand and metal ion dependent intricate folding landscape of Vc2 c-di-GMP riboswitch aptamer
Authors: Shin Ji-Yeon , Choi Seo-Ree , An So Young , Bang Kyeong-Mi , Song Hyun Kyu , Suh Jeong-Yong , Kim Nak-Kyoon
Published: December 2024

Riboswitches are RNAs that recognize ligands and regulate gene expression. They are typically located in the untranslated region of bacterial messenger RNA and consist of an aptamer and an expression platform. In this study, we examine the folding pathway of the Vc2 (Vibrio cholerae) riboswitch aptamer domain, which targets the bacterial secondary messenger cyclic-di-GMP. We demonstrated by nuclear magnetic resonance (NMR) and isothermal titration calorimetry that the stable folding of the Vc2 riboswitch requires an adequate supply of Mg2+, Na+ and K+ ions. We found that Mg2+ has a crucial role in the pre-folding of the aptamer, while K+ is essential for establishing the long-range G-C interactions and stabilizing the ligand binding pocket. Precise imino proton assignments revealed the progressive folding of the aptamer. The results indicate that the P2 helix consists of weaker and more dynamic base pairs compared to the P1b helix, allowing the rearrangement of the base pairs in the P2 helix during the folding process required for effective ligand recognition. This study provides a profound understanding riboswitch architecture and dynamics at the atomic level under physiological conditions as well as structural information on apo-state RNA.
Cu2+ mediates the oxidation of the transcription factor MscA to regulate the antioxidant defense of mycobacteria
Authors: Xiang Yuling , Zheng Jiachen , Liu Zhendong , Cui Xujie , Zhang Yunfan , Guo Minhao , Li Weihui
Published: December 2024

Copper (Cu), a trace element with redox activity, is both essential and toxic to living organisms. Its redox properties make it a cofactor for a variety of proteins, but it also causes oxidative stress, hence the need to maintain intracellular copper homeostasis. However, the role of copper in the regulation of antioxidant defense in bacteria remains unclear, and the involved transcription factors remain to be explored. In this study, we identified a novel transcription factor, MscA, that responded directly to Cu2+ to regulate the antioxidant defense of mycobacteria. Cu2+ directly bound to MscA to mediate oxidation and inhibit the DNA binding activity of MscA, subsequently downregulating the expression of antioxidant gene cluster to increase the accumulation of reactive oxygen species in mycobacteria, ultimately leading to oxidative damage to mycobacteria. Therefore, we firstly reported that the Cu2+ responsive transcription factor regulated the antioxidant defense in bacteria. This finding firstly and directly links the function of Cu2+ to the antioxidant defense of bacteria, and provides a new insight into bacterial antioxidant defense.
Therapeutic effect of novel drug candidate, PRG-N-01, on NF2 syndrome-related tumor
Authors: Chung Yeon-Ho , Park Soyoung , Lee Moonyoung , Lee Jongwon , Ji Yeongseon , Song Yi Jin , Woo Tae-Gyun , Shin Eunbyeol , Baek Songyoung , Hwang Young Jun , Kim Yuju , Kim Minju , Han Jin , Kim Hong-Rae , Choi Jungmin , Kim Bae-Hoon , Park Bum-Joon
Published: December 2024

Background

NF2-related schwannomatosis (NF2-SWN) is associated with multiple benign tumors in the nervous system. NF2-SWN, caused by mutations in the NF2 gene, has developed into intracranial and spinal schwannomas. Because of the high surgical risk and frequent recurrence of multiple tumors, targeted therapy is necessary. However, there are no approved drugs.

Methods

We examined the action mechanism of PRG-N-01, a candidate molecule for NF2-SWN, through the direct binding assay and mass spectrometry. For in vitro anti-proliferative experiments, primary cells derived from the NF2 mouse model and patient tumors were treated with PRG-N-01. The in vivo therapeutic and preventive efficacy was validated via intraperitoneal and oral administration in the NF2 mouse model (Postn-Cre; Nf2f/f). Gene expression profile in the DRG of the mouse model was explored by RNA sequencing. The pharmacological properties of PRG-N-01 were analyzed through the preclinical study.

Results

PRG-N-01 binds to the N-terminal extremity of TGFβR1 (TβR1) kinase domain, where TβR1 and RKIP interact, inhibiting the binding and preventing degradation of RKIP. In vivo administration in the mouse model suppressed schwannoma progression in the DRG. Early oral administration of the PRG-N-01 also demonstrated preventive effects on NF2-SWN. PRG-N-01 treatment suppressed tumor growth genes while upregulating genes related to for normal cell metabolism and Schwann cell differentiation in DRG. PRG-N-01 showed druggable properties through the preclinical study, including ADME, pharmacodynamics, pharmacokinetics, and toxicology.

Conclusions

Together, our study provides the rationale and critical data for a prospective clinical trial of PRG-N-01 in NF2-SWN patients indicating PRG-N-01 as a promising candidate for the treatment.
Maternal Smoking During Pregnancy Interacts With Genetic Factors to Increase Risk for Low Birth Weight but Not Harmful Offspring Smoking Behaviors in Europeans
Authors: Romero Villela Pamela N , Kelly Kristen M , Balbona Jared V , Ehringer Marissa A , Keller Matthew C
Published: December 2024

Introduction

Pregnant individuals who smoke face increased health risks because smoking harms both the mother and their developing offspring.

Aims and Methods

Using 307 417 Europeans from the UK Biobank, we examined whether exposure to maternal smoking during pregnancy (MSP) interacts with genetic risk to predict offspring birth weight (BW) and smoking behaviors. We investigated interactions between MSP and genetic risk at multiple levels: single variant, gene level, and polygenic score. We examined self-reported BW, smoking initiation status (SI), age of smoking initiation, cigarettes per day, and smoking cessation status.

Results

One locus tagged by single-nucleotide polymorphism rs72689499 on chromosome 14 reached significance for interaction with MSP on the multiplicative (log10) scale for BW (p = 5.13 × 10−9). In gene-level testing, three genes on chromosome 1 and one gene on chromosome 14 reached significance for interaction with MSP on both the additive and multiplicative scale for BW. These genes include PTCH2, EIF2B3, PLK3, and TSHR. Single-nucleotide polymorphism and gene-level results were insignificant for all offspring smoking behaviors. We also detected an interaction between polygenic risk for smoking and MSP on SI on both the additive (p = 4.4 × 10−5) and multiplicative (p = 1.0 × 10−5) scale. We found evidence of gene–environment correlation in the polygenic risk analysis using a post hoc t test which showed that MSP-exposed offspring had a higher SI polygenic risk scores than those unexposed to MSP (p = 5.9 × 10−623).

Conclusions

Our results support the main effect of MSP on BW and show a genetic interaction between MSP and genetic factors influencing BW.

Implications

We detected interactions between maternal smoking and genetic factors to influence birth weight; these interactions were detectable at both the single-nucleotide polymorphism and gene levels. Many of the genes detected to interact with maternal smoking to influence birth weight have other reported associations with height or smoking-related traits. For smoking initiation, we detected a negative interaction between maternal smoking and polygenic risk, as well as evidence of gene–environment correlation.
Serum uric acid and prediabetes progression and regression: a retrospective cohort study
Authors: He Yijia , Ye Miaomin , Xia Yin , Zhong Ziyi , Li Qian
Published: December 2024

Background

The impact of serum uric acid (SUA) levels on metabolic disorders, particularly concerning the development or reversal of prediabetes, is not well understood. While high uric acid is recognized for its association with metabolic disturbances, its specific influence on prediabetes progression and regression has been insufficiently explored. This study investigates how SUA levels correlate with the natural course of prediabetes, shedding light on its management.

Methods

A cohort of 3659 individuals diagnosed with prediabetes at Nanjing First Hospital was tracked over three years. Follow-up assessments included fasting plasma glucose and hemoglobin A1c (HbA1c) measurements. Serum uric acid was measured initially and categorized into quartiles (Q1 through Q4). To assess the impact of uric acid levels on shifting prediabetes status, methods such as restricted cubic spline, segmented regression, stratified analysis, and receiver operating characteristic curves were utilized in a multinomial logistic regression framework.

Results

At baseline, all 3659 participants had prediabetes; by the three-year mark, 2626 remained in this category, 523 reverted to normal fasting glucose (NFG), and 510 advanced to diabetes. After adjustment for potential confounders, a positive correlation was found between higher SUA levels and progression to diabetes (Odds ratio [OR] 1.182, 95% confidence interval [CI]: 1.095–1.276), with no significant link to reversion to NFG (OR: 0.987, 95% CI: 0.909–1.073).

Conclusion

Elevated SUA levels are linked with a higher likelihood of progressing from prediabetes to diabetes but do not significantly forecast a regression to NFG.
Comparative effectiveness of disease-modifying antirheumatic drugs for patients with cardiac sarcoidosis
Authors: Brooks Lisbeth , Kivlin William , Mohananey Divyanshu , Sabchyshyn Viktoriya , Putman Michael
Published: December 2024

Objectives

We aimed to evaluate the comparative efficacy of disease-modifying antirheumatic drugs (DMARDs) for patients with cardiac sarcoidosis.

Methods

We performed a retrospective cohort study of new users of methotrexate, mycophenolate or azathioprine for sarcoidosis using the US-based TriNetX electronic health records database from 2008 to 2023. Hazard ratios were calculated using inverse probability of treatment weighted Cox proportional hazards regressions to compare the efficacy of DMARDs with respect to delaying major adverse cardiac events among patients with cardiac sarcoidosis and preventing cardiac sarcoidosis from developing among patients with non-cardiac sarcoidosis.

Results

Among 3441 patients with sarcoidosis, 601 were defined as cardiac sarcoidosis and 2840 as non-cardiac sarcoidosis. The average age of the cohort was 52.1 years (standard deviation 11.9 years) and the majority were female (55.9%) and white (50.0%). Among patients with cardiac sarcoidosis at baseline, the risk of serious cardiac outcomes was similar for patients who initiated therapy with mycophenolate mofetil (HR 0.83, 95% CI 0.43–1.59) or azathioprine (HR 0.74, 95% CI 0.29–1.89) as compared with methotrexate. Among patients who did not have cardiac sarcoidosis at baseline, the risk of developing cardiac sarcoidosis was similar for patients who initiated therapy with mycophenolate mofetil (HR 1.11, 95% CI 0.46–2.66) and azathioprine (HR 0.54, 95% CI 0.15–1.91) as compared with methotrexate. Mycophenolate mofetil (HR 1.83, 95% CI 1.10–3.05) and azathioprine (HR 1.32, 95% CI 0.92–1.89) increased the risk of infection.

Conclusion

A strategy of methotrexate had a favorable safety profile in terms of infection risk and may be favored over azathioprine or mycophenolate mofetil for patients with sarcoidosis or cardiac sarcoidosis.
Geographic origin and evolution of dengue virus serotypes 1 and 3 circulating in Africa
Authors: Nyathi Sindiso , Rezende Izabela M , Walter Katharine S , Thongsripong Panpim , Mutuku Francis , Ndenga Bryson , Mbakaya Joel O , Agola Gladys , Vu David M , Bennett Shannon , Mordecai Erin A , Andrews Jason R , LaBeaud A Desiree
Published: December 2024

Despite the increasing burden of dengue in Kenya and Africa, the introduction and expansion of the virus in the region remain poorly understood. The objective of this study is to examine the genetic diversity and evolutionary histories of dengue virus (DENV) serotypes 1 and 3 in Kenya and contextualize their circulation within circulation dynamics in the broader African region. Viral RNA was extracted from samples collected from a cohort of febrile patients recruited at clinical sites in Kenya from 2013 to 2022. Samples were tested by polymerase chain reaction (PCR) for DENV presence. Five DENV-positive samples were serotyped, and complete viral genomes for phylogenetic inference were obtained via sequencing on Illumina platforms. Sequences generated in our study were combined with global datasets of sequences, and Bayesian and maximum likelihood methods were used to infer phylogenetic trees and geographic patterns of spread with a focus on Kenya and Africa as a whole. Four new DENV-1 and one new DENV-3 genomes were successfully sequenced and combined with 328 DENV-1 and 395 DENV-3 genomes from elsewhere for phylogenetic analyses. The DENV-1 sequences from our study formed a monophyletic cluster with an inferred common ancestor in 2019 (most recent common ancestor 2019 and 95% high posterior density 2018–19), which was closely related to sequences from Tanzania. The single DENV-3 sequence clustered with sequences from Tanzania and Kenya, was collected between 2017 and 2019 and was related to recent outbreaks in the region. Phylogenetic trees resolved multiple clades of DENV-1 and DENV-3 concurrently circulating in Africa, introduced in the early-to mid-2000s. Three DENV-1 and four DENV-3 clades are highlighted, introduced between 2000 and 2015. Phylogeographic models suggest frequent, independent importations of DENV lineages into Kenya and Africa from East and South-East Asia via distinct geographic pathways. DENV-1 and DENV-3 evolutionary dynamics in Africa are characterized by the cocirculation of multiple recently introduced lineages. Circulating lineages are introduced via distinct geographic pathways that may be centered around regional nexus locations. Increased surveillance is required to identify key regional locations that drive spread, and dengue interventions should focus on interrupting spread at these locations.
Development of A Novel Multiplex TaqMan Probe qPCR Assay Distinguishing Dikaryotic ITS rDNA Types of Sclerotium rolfsii (=Agroathelia rolfsii) and S. delphinii
Authors: Lee Dong Jae , Choi Young-Joon
Published: December 2024

Sclerotium rolfsii (=Agroathelia rolfsii) and S. delphinii are globally ubiquitous and prevalent soil-borne pathogens. These species are distinguishable by the morphology of their sclerotia formed on artificial media. However, this distinction requires prior pure isolation, complicating direct identification from diseased plants or soil samples. Additionally, each species contains two distinct ITS ribosomal DNA types in a dikaryotic cell, further complicating their identification through sequence analysis. To address this issue, we developed a novel multiplex qPCR method utilizing TaqMan probes and primers. This method specifically targets the two ITS types unique to each species, effectively distinguishing between these pathogens and differentiating them from non-target soil-borne fungal and oomycete pathogens. Its efficiency and sensitivity were confirmed through their detections in artificially inoculated plants and soil samples. Our multiplex qPCR technique offers a precise and reliable approach for the simultaneous detection and differentiation of S. rolfsii and S. delphinii, significantly improving disease surveillance and facilitating timely, effective disease management.
Embracing Neurodiversity in the Nursing Workforce
Authors: Azar Najood G. , Taha Asma A.
Published: December 2024

Neurodivergent nurses bring unique strengths that can enhance patient care.
A Conversation with Mary Jarden
Authors: McSpedon Corinne
Published: December 2024

From the United States to Denmark, an oncology nurse's path to leadership
Examining Shift Length and Fatigue
Authors: Farmer Meredith L. , Hoffman Jacqueline , Vance Ashlee , Li Yin , Bell Tracey R.
Published: December 2024

Background:

Neonatal advanced practice providers (APPs) often work prolonged hours in high-acuity neonatal intensive care units (NICUs). It is imperative to understand how fatigue affects the APP’s ability to react quickly following long shifts. There is a lack of data on the effects of shift length and fatigue on neonatal APP job performance and clinical decision-making.

Purpose:

The purpose of this study was to describe the variation in shift length, knowledge-based competency, personal well-being, and behavioral alertness for neonatal APPs.

Methods:

This study evaluated neonatal APPs before and after a clinical shift. Provider well-being was assessed during the pre-survey. Pretest-posttest surveys evaluated neonatal APP’s psychomotor vigilance skills and knowledge. Participants completed an online, anonymous questionnaire to answer a series of knowledge-based questions before and after their shift, along with a psychomotor vigilance test (PVT). A paired t test analysis evaluated the pre- and post-shift PVT values and knowledge-based test scores.

Results:

Overall, 61 pre-surveys and 42 post-surveys were completed; 36 were matched by participants pre- to post-survey. The mean between pre- and post-knowledge-based questions was statistically significant, with higher posttest scores. There was no statistical difference noted in the paired t test analysis of the PVT values.

Implications for Practice and Research:

The small sample size may limit the generalizability of findings, but these results may indicate that shift length does not affect psychomotor vigilance or knowledge-based competency. It is vital that future work assess the associations between APP shift length, fatigue, and critical decision-making.
Brunelli (Dorsoulnar) Flap for the Reconstruction of Defect of the Thumb Nail Unit After Oncological Resections With Mohs Micrographic Surgery
Authors: Mesa Felipe , Leal Oscar , Ramos María Elena
Published: December 2024

Background:

The Brunelli flap is an option in the reconstruction of the thumb after trauma or oncological resections. The arc of movement of the flap makes it possible to resolve defects in the proximal, palmar, dorsal, and lateral regions.

Methods:

We present a case series of 11 patients in whom a Brunelli flap was performed for postoncological reconstruction, melanoma in situ, and invasive squamous cell carcinoma of the thumb nail unit associated with Mohs micrographic surgery. This combination has not been described before.

Results:

The reconstruction was carried out using a Brunelli flap, incorporating certain variations to the original technique. Clinical follow-up was performed during a 1-year period. All flaps showed good viability. In 3 flaps, there was mild distal suffering that resolved with local healing. Three patients presented hypersensitivity in the distal part, which was managed with physical therapy. The functionality of the thumb was not altered in any case, and there were no complications in the donor site. No tumor recurrence was documented in any patient.

Conclusions:

The use of the Brunelli flap to reconstruct the nail unit after an oncological resection with Mohs surgery is a good alternative. The advantages include a dorsal artery as a constant vessel and a homodigital flap that does not cause morbidity in the donor area, and with Mohs surgery, amputation is avoided. Disadvantages include lack of sensation of the flap. Some limitations of our study are the sample size and lack of long-term follow-up.
Prevalence of metabolic dysfunction–associated steatotic liver disease and fibrosis defined by liver elastography in the United States using National Health and Nutrition Examination Survey 2017-March 2020 and August 2021-August 2023 data
Authors: Unalp-Arida Aynur , Ruhl Constance E.
Published: December 2024

Background and Aims:

Steatotic liver disease (SLD) is a significant public health burden. Previously, we estimated prepandemic SLD prevalence determined by transient elastography-assessed hepatic steatosis and fibrosis in the United States. We now estimate the prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD) and examine associations with lifestyle, socioeconomic, and other factors.

Approach and Results:

Liver stiffness and controlled attenuation parameters were assessed on 13,538 non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic men and women aged 20 years and over in the National Health and Nutrition Examination Survey 2017 to March 2020 and August 2021 to August 2023. The prevalence of SLD (controlled attenuation parameter >300 dB/m) was 28.7%, fibrosis (liver stiffness >8 kPa) was 11.3%, and MASLD was 25.6%. Between the 2 survey cycles, the age-standardized SLD prevalence was not significantly different, MASLD prevalence decreased (26.8%–23.6%), and fibrosis prevalence increased (10.4%–12.7%). In multivariable-adjusted analysis, both MASLD and fibrosis were associated with diabetes, higher body mass index, higher waist-to-hip ratio, elevated blood pressure, and inversely associated with non-Hispanic Black race-ethnicity. MASLD was also associated with male sex, non-Hispanic Asian race-ethnicity, prediabetes, higher total cholesterol, lower HDL cholesterol, and greater sedentary lifestyle. Fibrosis was also associated with SLD, lower total cholesterol, and less education.

Conclusions:

In the US population, MASLD and fibrosis prevalence are high along with obesity and diabetes. Our findings suggest that early detection of chronic liver disease and targeting lifestyle and other modifiable risk factors may slow disease progression toward advanced fibrosis and cirrhosis.
Over 100 Fontan Patients on Systemic Ventricular Assist Device Support: An ACTION Update
Authors: Chen Sharon , Simpson Kathleen E. ,   on Behalf of ACTION Learning Network Investigators
Published: December 2024

As the Fontan population grows, understanding successful strategies for ventricular assist device (VAD) support of the failing Fontan circulation is needed. We performed a retrospective analysis of patients with Fontan circulation and systemic VAD support in the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry. Competing outcomes and Kaplan–Meier estimated survival methods were used. Between January 2012 and December 2022, 106 Fontan patients underwent VAD implant (median age 10 years, 20% age ≥18 years). At time of implant, 58% were on greater than or equal to 2 inotropes, 26% on extracorporeal membrane oxygenation (ECMO), and 41% intubated. Since 2018, there have been more patients implanted at INTERMACS profile 1 or 2 (88% vs. 71%, p = 0.02) and on inotropic support (95% vs. 76%, p = 0.01). Median duration of VAD support was 113 (interquartile range (IQR): 43–266) days. At 12 months post-VAD implant, 53% were transplanted, 27% were alive on device, 2% had successful recovery, and 18% had died. Overall, 75% experienced greater than or equal to 1 adverse event, with bleeding, infection, and neurologic dysfunction most common. Despite high acuity at the time of VAD implant and high rate of adverse events, the majority of Fontan patients were transplanted or still alive on device at 12 months post-VAD implant.