bluuebunny/crossref_metadata_2025 huggingface dataset:
The physical properties of two potential targets for space missions: (155140) 2005 UD and (612267) 2001 SG286
Authors: Gherase R M , Popescu M , Vaduvescu O , Wilson T G , de León J , Lorenzi V , Licandro J , Morate D , Simion G , Macías A Aznar , Dumitru B A
Published: November 2024

The ground-based characterization of asteroids is a key step for planning their exploration. The near-Earth asteroid 155140 (2005 UD) is a potential flyby target of Japan Aerospace Exploration Agency’s DESTINY+ (Demonstration and Experiment of Space Technology for INterplanetary voYage with Phaethon fLyby and dUst Science) mission, while (612267) 2001 SG286 has been considered as a possible target for in-situ exploration. We aim to determine their physical properties using the observations obtained with various telescopes from Canary Islands Observatory. For 2005 UD, we confirmed the two peak light curve, a rotation period of 5.224 $\pm$ 0.003 h and an amplitude of 0.34 mag. However, a three peak solution seemed also to fit the light curve, but this was discarded as implausible. Using the obtained visible to near-infrared spectrum we classified it as a Cb type, and we found a spectral matching with heated carbonaceous chondrite meteorites of CM2 type. The thermal emission flux at 2.2 $\mu \mathrm{ m}$ points to an albedo of $p_V = 0.06~\pm ~0.02$. There are significant differences in the spectrum of 2005 UD compared to that of (3200) Phaeton, hypothesized as its parent body. The accurate visible spectrum obtained with the Gran Telescopio Canarias indicate that 2001 SG286 is an S-type asteroid. The photometric data obtained with Isaac Newton Telescope suggest a rotation period of 12.30 $\pm$ 0.01 h and an amplitude of 0.64 mag. With these observations we found its absolute magnitude $H$  = 21.4 $\pm$ 0.3, and estimate its size as 160 $\pm$ 45 m.
RBPWorld for exploring functions and disease associations of RNA-binding proteins across species
Authors: Liao Jian-You , Yang Bing , Shi Chuan-Ping , Deng Wei-Xi , Deng Jin-Si , Cen Mei-Feng , Zheng Bing-Qi , Zhan Zi-Ling , Liang Qiao-Ling , Wang Ji-En , Tao Shuang , Lu Daning , Liang Maojin , Zhang Yu-Chan , Yin Dong
Published: November 2024

RNA-binding proteins (RBPs) play key roles in a wide range of physiological and pathological processes. To facilitate the investigation of RBP functions and disease associations, we updated the EuRBPDB and renamed it as RBPWorld (http://research.gzsys.org.cn/rbpworld/#/home). Leveraging 998 RNA-binding domains (RBDs) and 87 RNA-binding Proteome (RBPome) datasets, we successfully identified 1 393 413 RBPs from 445 species, including 3030 human RBPs (hRBPs). RBPWorld includes primary RNA targets of diverse hRBPs, as well as potential downstream regulatory pathways and alternative splicing patterns governed by various hRBPs. These insights were derived from analyses of 1515 crosslinking immunoprecipitation-seq datasets and 616 RNA-seq datasets from cells with hRBP gene knockdown or knockout. Furthermore, we systematically identified 929 RBPs with multi-functions, including acting as metabolic enzymes and transcription factors. RBPWorld includes 838 disease-associated hRBPs and 970 hRBPs that interact with 12 disease-causing RNA viruses. This provision allows users to explore the regulatory roles of hRBPs within the context of diseases. Finally, we developed an intuitive interface for RBPWorld, facilitating users easily access all the included data. We believe that RBPWorld will be a valuable resource in advancing our understanding of the biological roles of RBPs across different species.
StreptomeDB 4.0: a comprehensive database of streptomycetes natural products enriched with protein interactions and interactive spectral visualization
Authors: Feng Yue , Qaseem Ammar , Moumbock Aurélien F A , Pan Shuling , Kirchner Pascal A , Simoben Conrad V , Malange Yvette I , Babiaka Smith B , Gao Mingjie , Günther Stefan
Published: November 2024

Streptomycetes remain an important bacterial source of natural products (NPs) with significant therapeutic promise, particularly in the fight against antimicrobial resistance. Herein, we present StreptomeDB 4.0, a substantial update of the database that includes expanded content and several new features. Currently, StreptomeDB 4.0 contains over 8500 NPs originating from ∼3900 streptomycetes, manually annotated from ∼7600 PubMed-indexed peer-reviewed articles. The database was enhanced by two in-house developments: (i) automated literature-mined NP–protein relationships (hyperlinked to the CPRiL web server) and (ii) pharmacophore-based NP–protein interactions (predicted with the ePharmaLib dataset). Moreover, genome mining was supplemented through hyperlinks to the widely used antiSMASH database. To facilitate NP structural dereplication, interactive visualization tools were implemented, namely the JSpecView applet and plotly.js charting library for predicted nuclear magnetic resonance and mass spectrometry spectral data, respectively. Furthermore, both the backend database and the frontend web interface were redesigned, and several software packages, including PostgreSQL and Django, were updated to the latest versions. Overall, this comprehensive database serves as a vital resource for researchers seeking to delve into the metabolic intricacies of streptomycetes and discover novel therapeutics, notably antimicrobial agents. StreptomeDB is publicly accessible at https://www.pharmbioinf.uni-freiburg.de/streptomedb.
Sci-ModoM: a quantitative database of transcriptome-wide high-throughput RNA modification sites
Authors: Boileau Etienne , Wilhelmi Harald , Busch Anne , Cappannini Andrea , Hildebrand Andreas , Bujnicki Janusz M , Dieterich Christoph
Published: November 2024

We present Sci-ModoM, the first next-generation RNome database offering a holistic view of the epitranscriptomic landscape. Sci-ModoM has a simple yet powerful interface, underpinned by FAIR data principles, a standardized nomenclature, and interoperable formats, fostering the use of common standards within the epitranscriptomics community. Sci-ModoM provides quantitative measurements per site and dataset, enabling users to assess confidence levels based on score, coverage, and stoichiometry. Data in Sci-ModoM is directly traceable to its sources. Users can Search and Compare over six million modifications across 156 datasets, Browse or download datasets, and retrieve metadata. A comparison tool offers a novel and unique opportunity to compare modifications site-wise across datasets, with the ability to securely upload and compare user data against latest published research. Sci-ModoM empowers researchers, including non-experts, to access a broad spectrum of recent quantitative RNA modification data, thereby enhancing the utility and impact of latest discoveries, and opening new avenues in biological and medical research.
Impact of the US Maternal Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis (Tdap) Vaccination Program on Preventing Pertussis in Infants 2 to <6 Months of Age: A Case-Control Evaluation
Authors: Skoff Tami H , Rubis Amy B , Kirley Pam Daily , Scherzinger Karen , McMahon Melissa , McGuire Suzanne , Kudish Kathy , Cieslak Paul R , Shang Nong , Hariri Susan
Published: November 2024

Background

To protect infants aged <2 months against pertussis, the United States recommends Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) vaccination during each pregnancy. Data are limited on the strategy's effectiveness against pertussis in infants aged ≥2 months.

Methods

Pertussis case infants aged 2 to <6 months with cough onset between 1 January 2011 and 31 December 2014 were identified in 6 US states. Controls were 2 to <6 months of age, hospital matched, and selected by birth certificate. Mothers were interviewed to collect demographic and healthcare information. Provider-verified vaccination history was obtained for infants and mothers. Adjusted odds ratios (aORs) were calculated using conditional logistic regression; overall vaccine effectiveness (VE) was estimated as (1 − aOR)×100. To describe maternal Tdap VE modified by infant DTaP (diphtheria and tetanus toxoids and acellular pertussis) doses, case-control sets were unmatched, and a time-to-event analysis was conducted through a generalized linear mixed model.

Results

A total of 335 cases and 927 controls were enrolled. The overall adjusted VE estimate for Tdap during pregnancy was 45.6% (95% confidence interval [CI], 5.8%–68.5%) and increased slightly, but not significantly, against infant hospitalization (55.7% [−116.8% to 90.9%]). Although point estimates were not significant, VE was modified by infant DTaP doses (58.8% [95% CI, −6.0% to 84.0%] for 0 DTaP doses, 30.5% [−21.4% to 60.2%] for 1 dose, and 3.2% [−170.8% to 65.4%] for 2 doses).

Conclusions

Our study suggests that there is some benefit of maternal Tdap vaccination beyond the first 2 months of life, however, on-time vaccination of infants remains critical to maintain protection from pertussis.
Prescribing Patterns of High Opioid and Antibiotic Prescribers, Washington State, 2021: Do Some Prescribers Have Trouble Saying No?
Authors: Evans David Trey , Kamenar Katarina , Zering Jessica , D’Angeli Marisa , Stohs Erica J
Published: November 2024

Among Washington State emergency and family medicine physicians, high prescribers of opioids were 2.9 times more likely to be high prescribers of antibiotics in the Medicare Part D population. The inverse relationship showed the same association. Antimicrobial and opioid stewards should collaborate on shared goals to implement effective interventions.
EXECUTER1 and singlet oxygen signaling: A reassessment of nuclear activity
Authors: Liu Kaiwei , Zhao Huan , Lee Keun Pyo , Yu Qing , Di Minghui , Wang Liangsheng , Kim Chanhong
Published: November 2024

Chloroplasts are recognized as environmental sensors, capable of translating environmental fluctuations into diverse signals to communicate with the nucleus. Among the reactive oxygen species produced in chloroplasts, singlet oxygen (1O2) has been extensively studied due to its dual roles, encompassing both damage and signaling activities, and the availability of conditional mutants overproducing 1O2 in chloroplasts. In particular, investigating the Arabidopsis (Arabidopsis thaliana) mutant known as fluorescent (flu) has led to the discovery of EXECUTER1 (EX1), a plastid 1O2 sensor residing in the grana margin of the thylakoid membrane. 1O2-triggered EX1 degradation is critical for the induction of 1O2-responsive nuclear genes (SOrNGs). However, a recent study showed that EX1 relocates from chloroplasts to the nucleus upon 1O2 release, where it interacts with WRKY18 and WRKY40 (WRKY18/40) transcription factors to regulate SOrNG expression. In this study, we challenge this assertion. Our confocal microscopy analysis and subcellular fractionation assays demonstrate that EX1 does not accumulate in the nucleus. While EX1 appears in nuclear fractions, subsequent thermolysin treatment assays indicate that it adheres to the outer nuclear region rather than localizing inside the nucleus. Furthermore, luciferase complementation imaging and yeast 2-hybrid assays reveal that EX1 does not interact with nuclear WRKY18/40. Consequently, our study refines the current model of 1O2 signaling by ruling out the nuclear relocation of intact EX1 as a means of communication between the chloroplast and nucleus.
MYB168 and WRKY20 transcription factors synergistically regulate lignin monomer synthesis during potato tuber wound healing
Authors: Yang Ruirui , Wang Qihui , Wang Ying , Zhang Xuejiao , Zheng Xiaoyuan , Li Yongcai , Prusky Dov , Bi Yang , Han Ye
Published: November 2024

Lignin is a critical component of the closing layer of the potato (Solanum tuberosum L.) tuber during healing; however, the molecular mechanism of its formation remains poorly understood. To elucidate the molecular mechanism of tuber healing, we screened the genes encoding transcription factors that regulate lignin synthesis(StMYB24/49/105/144/168, StWRKY19/20/22/23/34) and the key genes involved in lignin monomer synthesis (PHENYLALANINE AMMONIA LYASE 5 (StPAL5) and CINNAMYL ALCOHOL DEHYDROGENASE 14 (StCAD14)) for induced expression after wounding using transcriptome data. Dual-luciferase assay, yeast one-hybrid, electrophoretic mobility shift assay, and chromatin immunoprecipitation-qPCR assays revealed that StMYB168 could bind directly to the StPAL5 and StCAD14 promoters to activate their expression and that StWRKY20 enhanced this regulation with a synergistic effect. Y2H, bimolecular fluorophore complementation, and coimmunoprecipitation assays showed that StMYB168 interacted with StWRKY20 to form a MYB-WRKY complex. Furthermore, transient overexpression (OE) of StMYB168 and StWRKY20 in Nicotiana benthamiana leaves upregulated the expression of NbPAL and NbCAD10 and promoted lignin accumulation in the leaves. In addition, OE of StWRKY20 and StMYB168 together resulted in higher expression levels of NbPAL and NbCAD10 and higher levels of lignin monomer and total lignin. In contrast, silencing of StMYB168 and StWRKY20 in potato significantly reduced the lignin content of wounded tubers. In conclusion, StMYB168 and StWRKY20 are important regulators of lignin biosynthesis in potato tubers during healing and can positively regulate lignin biosynthesis by forming a complex. The elucidation of this regulatory module provides information on the regulatory mechanism of lignin monomer synthesis in wounded tubers at the transcriptional level.
Kaon Experiments
Authors: Yamanaka Taku
Published: November 2024

After $CP$ violation was discovered in the $K_L \rightarrow \pi ^+ \pi ^-$ decay, many theories were proposed to explain it, and the Kobayashi–Maskawa model and the Superweak model lasted for many years as strong candidates. High-precision kaon experiments with many new techniques and improvements rejected the Superweak model and supported the Kobayashi–Maskawa model in the 1990s. Since then, rare kaon decay experiments have studied $K \rightarrow \pi \nu \overline{\nu }$ decays to search for $CP$ violation caused by new physics beyond the Standard Model. Various techniques have been developed to increase the sensitivity and to suppress backgrounds.
A scoping review of food consumer aspects in transitioning to a safe and just agrifood system
Authors: Moghayer Saeed , Manouchehrabadi Behrang , Tiboldo Giulia , Ferrer-Pérez Hugo , Kozicka Marta , van Dijk Michiel , Farina Giuditta , Castellari Elena , Moro Daniele , Philippidis George
Published: November 2024

The agrifood system holds the key to identifying potential transformative pathways to achieve prosperity for all within the limits of the planet's natural resources, thereby fostering a safe and just operating system (SJOS) for future generations. The agrifood system is currently not on the right track to meet this ambition. Food–consumer processes such as preference shifts toward healthy diets and substantial reductions in food losses and waste could help to avoid severe environmental degradation and decrease overall mortality, although it remains unclear whether such transitional developments are entirely compatible with socially responsible thresholds. In this paper, we conduct a scoping review approach to map the evidence on the underlying drivers of such demand-side processes in the context of an SJOS with the aim to provide insights on how to transform the EU agrifood system. This review specifically examines how consumer aspects influence the SJOS, rather than exploring the bidirectional relationship. We used a scoping review approach to select relevant studies. The selected papers were subjected to quantitative and qualitative analyses. As a result, we extract insights and draw lessons from the role of food–consumer processes in the transition toward a more SJOS for the agrifood system.
Noise test of an electromagnetic antenna for low frequency scattered gravitational waves
Authors: Cruise Adrian Michael , Flack Robert
Published: November 2024

Gravitational waves proved hard to detect experimentally and yet carry high energy fluxes. Conversely, the technology for electromagnetic waves is sophisticated, easily available, and highly sensitive. Various proposals have been made to use the conversion of a gravitational wave into an electromagnetic wave to generate signals that could be detected. We present test results from a novel electromagnetic antenna, efficient at the very low frequencies needed to explore the signals from supermassive black holes mergers. These will eventually be studied by the laser interferometric space antenna (LISA) at wavelengths between $10^{8}$ and $10^{11}$ m. Common forms of electromagnetic antennae are only efficient when the ratio of wavelength, $\lambda$, to antenna length, L, is roughly between 0.1 and 10. This paper proposes a scheme for a realistic ground-based electromagnetic antenna, ‘the resistive antenna’, which operates efficiently at a ratio $\frac{\lambda }{L}$ of more than $10^{6}$. The first estimates of ambient noise at these low frequencies from field trials of such a device are presented. The measured levels of ambient noise result in this detection scheme having a sensitivity much worse than LISA. The antenna design described in this communication may also have application in other fields.
Male fertility is preserved following ixekizumab treatment—a real-life pilot study
Authors: Micu Mihaela C , Farina Nicola , Decean Hana P , Micu Alexandru , Surd Stela , Gîrlovanu Marinela , Andone-Rotaru Bianca , Dagna Lorenzo
Published: November 2024

Introduction

Preserving fertility is crucial when managing male patients with spondyloarthritis (SpA) and/or psoriasis (PsO), especially in young men. Chronic inflammation, hormonal dysregulation and immunosuppressive therapies can negatively impact male fertility. Over the past decades, positive data have emerged regarding the reproductive safety of various therapies in men. Ixekizumab (IXE), a high-affinity monoclonal antibody targeting IL-17A, has shown a safe profile for male fertility in small studies. This pilot study assesses the impact of IXE treatment on sperm parameters in SpA and/or PsO patients in a real-world setting.

Methods

Consecutive adult male SpA and/or PsO patients eligible for or undergoing IXE treatment were prospectively enrolled. Demographic data, disease characteristics, laboratory assessments, comorbidities and previous treatments were recorded. Sperm analysis was conducted after a minimum of 6 months of IXE treatment, and also before treatment inititation in a subgroup of patients. Parallel sperm evaluations were performed in a control group of healthy donors.

Results

Ten patients were enrolled: eight with SpA and two with PsO. After 6 months of IXE treatment, all patients had normal sperm parameters. One SpA and PsO patient with baseline oligozoospermia showed normal parameters at follow-up and achieved a successful pregnancy post-treatment. Compared with controls, IXE-treated patients had lower sperm concentrations but higher vitality.

Conclusion

In our limited-size pilot study on SpA and PsO patients, IXE exposure did not impair male fertility. Sperm parameters remained within normal ranges after a minimum of 6 months of treatment. Early IXE treatment may preserve or potentially reverse fertility impairment.
Taxation of foreign trusts in Greece/Tax incentives for the transfer of residence of individuals to Greece
Authors: Patiti Magdalini
Published: November 2024

The present overview provides a summary of the Greek tax regime applicable to foreign trusts. Up until 2017, the taxation of foreign trusts was largely left unregulated in the Greek tax system, which can be attributed to the fact that trusts, being a common-law concept, are not recognized by Greek legislation. Despite the uncertainties, foreign trusts were often used as structures for wealth management or estate planning. The guidelines provided in 2017 were thus eagerly awaited to provide clarity on a matter that was left unregulated for decades and can therefore only be considered as a very positive development. Nevertheless, certain aspects raise concern. This overview also summarizes the Greek Tax Incentive Regimes, which have been met with great demand from foreign residents seeking to transfer their (tax) residence to Greece.
Epigenetic modification of IGF2/H19 imprinting control region regulates PGC-1α/PI3K/AKT2 pathway in a rat model of intrauterine growth restriction
Authors: Liao Lihong , Zhou Xiuyun , Zhang Meihui , Lin Tulian , Long Wenjun , Yan Yaqin , Ning Qin , Luo Xiaoping
Published: November 2024

Background:

Intrauterine growth restriction (IUGR) is associated with adverse metabolic outcomes during adulthood. Histone modifications and changes in DNA methylation-affected genes are important for fetal development. This study aimed to confirm the epigenetic mechanisms in IUGR.

Methods:

IUGR models were established in Sprague–Dawley rats using a maternal nutritional restriction approach during pregnancy. The abundance of insulin-like growth factor 2 (IGF2), phosphoinositide 3-kinase (PI3K), AKT serine/threonine kinase 2 (AKT2), and PPAR gamma coactivator 1 alpha (PGC-1α) was examined by real-time polymerase chain reaction (RT-PCR) and Western blotting analysis. Chromatin immunoprecipitation RT-PCR was employed to analyze histone modification in CCCTC-binding factor (CTCF)1–4 binding sites of the IGF2/H19 imprinting control region (ICR). The methylation states of CTCF1–4 binding sites were studied by pyrosequencing.

Results:

The IUGR models were constructed successfully. IGF2 mRNA abundance in the placenta, fetal liver, and newborn liver was decreased in the IUGR group (P <0.01). Meanwhile, as compared with the control group, the expression levels of AKT2, PI3K, and PGC-1α were lower in newborn and 8-week-old livers in the IUGR group (P <0.05). In addition, knocking down IGF2 reduced the protein expression levels of AKT2-P and PGC-1α (P <0.05). In CTCF binding sites 1-4 of the IGF2/H19 ICR, AcH3 enrichment was significantly lower in CTCF1-3 in newborn and 8-week-old IUGR rats. H3K4me3 enrichment was significantly lower in the CTCF1–4 of newborn and 8-week-old IUGR groups (P <0.01). H3K9me2 enrichment was significantly higher in the IUGR group (P <0.01). The CpG dinucleotide methylation levels of CTCF1 and CTCF3, but not those of CTCF2 and CTCF4 binding sites in IUGR rat fetal, 4-week old, and 8-week-old livers decreased significantly (P <0.05).

Conclusion:

The methylation status and histone modification in the IGF2/H19 ICR are related to growth and lipid metabolism via the PGC-1α/PI3K/AKT2 pathway in IUGR rats.
Engineering and targeting potential of CAR NK cells in colorectal cancer
Authors: Khawar Muhammad Babar , Afzal Ali , Dong Shuangshuang , Si Yue , Sun Haibo
Published: November 2024

Colorectal cancer (CRC), a major global health concern, necessitates innovative treatments. Chimeric antigen receptor (CAR) T cells have shown promise, yet they grapple with challenges. The spotlight pivots to the rising heroes: CAR natural killer (NK) cells, offering advantages such as higher safety profiles, cost-effectiveness, and efficacy against solid tumors. Nevertheless, the specific mechanisms underlying CAR NK cell trafficking and their interplay within the complex tumor microenvironment require further in-depth exploration. Herein, we provide insights into the design and engineering of CAR NK cells, antigen targets in CRC, and success in overcoming resistance mechanisms with an emphasis on the potential for clinical trials.
Synchronous Pulmonary Langerhans Cell Histiocytosis and Multiple Cutaneous Reticulohistiocytomas With a Common BRAF-V600E/D Mutation Driver
Authors: Parra Ourania , Georgantzoglou Natalia , Green Donald , Wilson Jessica G. , Linos Konstantinos
Published: November 2024

Histiocytoses constitute a group of heterogeneous disorders characterized by involvement of variable organs by neoplastic macrophage or dendritic cells. They may affect both adults and children with a predilection to the skin, bone, lungs, lymph nodes, and CNS. The coexistence of different types of histiocytoses in the same patient is an extremely rare phenomenon. We describe a very rare case of co-occurring pulmonary Langerhans cell histiocytosis with multiple cutaneous reticulohistiocytomas with a common BRAF-V600E mutation as the driver genetic event in both the lung and skin lesions. The presence of a common BRAF-V600E mutation provides evidence of their clonal relation and contributes to our understanding in the pathogenesis of multiple, co-occurring histiocytic proliferations.
The Ubiquitin Ligase HERC2 Promotes Ang II-Induced Cardiac Hypertrophy Through Destabilization of MeCP2 to Enhance Lin28a Expression
Authors: Zhou Bin , Fu Hui-fan , Niu Jiang-feng , Deng Wei , Deng Fu-mou , Zhou Zhi-dong , Zhou Wei , Xiong Qinggen , Li Chang
Published: November 2024

Homologous to the E6-AP carboxy terminus-type E3 ubiquitin ligases participate in the progression of cardiovascular diseases. HERC2 has been reported to play critical roles in many pathologic processes, but its role in cardiac hypertrophy remains unclear. In this study, we observed that the expression and activity of HERC2 were significantly upregulated in hypertrophic hearts and angiotensin II (Ang II)-stimulated primary cardiomyocytes. Knockdown of HERC2 in cardiomyocytes significantly alleviated the myocardial hypertrophy induced by Ang II. Conversely, cardiac-specific overexpression of HERC2 aggravated Ang II-induced cardiac hypertrophy in vitro and in vivo. Furthermore, we demonstrated that HERC2 promoted cardiac hypertrophy through increasing the expression of lin-28 homologue A (Lin28a), an RNA-binding protein that regulates pathologic cardiac hypertrophic. Knocking down Lin28a attenuated Ang II-induced myocardial hypertrophy and abolished the increase in myocardial hypertrophy by overexpression of HERC2. Further investigation indicated that HERC2 promoted the expression level of Lin28a by reducing methyl-CpG binding protein 2 (MeCP2), a transcriptional suppressor of Lin28a. We also showed that the prohypertrophic effect of HERC2 was partially dependent on MeCP2 inhibition. Mechanistically, HERC2 directly bound with MeCP2, and promotes its K48-linked polyubiquitination and degradation. Combined, these findings demonstrate that HERC2 plays a crucial role in pathologic cardiac hypertrophy, thereby indicating that targeting the HERC2/MeCP2/Lin28a axis is a potential strategy for heart failure therapy.
Genetic Estimates of Correlation and Causality Between Keratoconus and Osteoarthritis
Authors: Han Tian , Han Xiaosong , Liu Liu , Wang Yuliang , Peng Xiaoliao , Zhou Xingtao
Published: November 2024

Purpose:

The relationship between keratoconus (KC) and osteoarthritis (OA) has been hypothesized, yet the causal link remained obscure. We aimed to evaluate the genetic correlation and causality between KC and OA through a genetic perspective.

Methods:

Linkage Disequilibrium Score Regression and bidirectional 2-sample Mendelian randomization (MR) analysis were conducted. Data were used from genome-wide association study on KC (4669 cases and 116,547 controls), OA (encompassing 24,955 patients with knee OA, 15,704 patients with hip OA, 39,427 patients with knee or hip OA, and 378,169 control participants), and KC data in the FinnGen consortium for replication and meta-analysis. Simple model, weighted model, inverse-variance weighted, weighted median, and MR-Egger regression were employed to assess the causal effects. MR pleiotropy residual sum and outlier method, MR-Egger method, and leave-one-out analysis were also applied to detect pleiotropy.

Results:

No statistically significant genetic correlation between KC and OA (all P > 0.05) were observed. MR estimates obtained from all 5 methods after meta-analysis revealed nonsignificant odds ratio values of KC-related traits to knee OA, hip OA, and OA (all adjusted P > 0.05). No evidence of causal relationships of knee and hip OA with KC-related traits was detected after meta-analysis of all 5 MR methods (all adjusted P > 0.05).

Conclusions:

The large MR analysis indicated that KC may not be causally associated with a risk of OA.
Femtosecond Laser-Assisted Graft Preparation and Implantation of Corneal Allogeneic Intrastromal Ring Segments for Corneal Ectasia: 1-Year Results
Authors: Bteich Yara , Assaf Jad F. , Müller Fabian , Gendy Jeremiah E. , Jacob Soosan , Hafezi Farhad , Awwad Shady T.
Published: November 2024

Purpose:

To evaluate the outcomes of patients treated with corneal allogeneic intrastromal ring segments cut with femtosecond laser (Femto-CAIRS) without concomitant corneal crosslinking.

Methods:

Patients with keratoconus treated with Femto-CAIRS at the American University of Beirut Medical Center were included (May 2022–January 2023). A proprietary software program was developed on the femtosecond laser to cut allogeneic segments. Visual, refractive, tomographic, aberrometric, and epithelial data by anterior segment optical coherence tomography were measured at baseline and 1, 3, 6, and 12 months postoperatively.

Results:

20 eyes of 15 patients were included and followed up for 12 months. The manifest refraction spherical equivalent and cylinder improved from −6.79 ± 4.9 diopter (D) and −4.25 ± 1.8 D to −1.88 ± 2.9 D (P < 0.001) and −2.64 ± 1.4 D (P = 0.01) 12 months postoperatively, respectively. 75% of eyes gained 3 or more corrected distance visual acuity lines, most of which (65%) gained 4 lines or more 12 months postoperatively. The maximum keratometry and vertical coma decreased by 5.2 D (P < 0.001) and 1 μm (P = 0.001), respectively, 3 months postoperatively and remained stable until 12 months. The largest anterior stromal elevation over the central 5-mm diameter decreased from 36.0 ± 18.2 μm preoperatively to 19.9 ± 9.25 μm at 1 week postoperatively (P < 0.001) and remained relatively stable. Epithelial thickness over the cone increased relative to baseline starting 1 month postoperatively and becoming stable after 6 months while the mean epithelial thickness central to the ring peaked at 1 month after which it decreased to reach a plateau at 6 months.

Conclusions:

The Femto-CAIRS procedure improves visual and tomographic parameters and allows repeatable and safe results with the possibility of customization for individualized management.
Widespread pain phenotypes impact treatment efficacy results in randomized clinical trials for interstitial cystitis/bladder pain syndrome: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain network study
Authors: Farrar John T. , Locke Kenneth T. , Clemens J. Quentin , Griffith James W. , Harte Steven E. , Kirkali Ziya , Kreder Karl J. , Krieger John N. , Lai H. Henry , Moldwin Robert M. , Mullins Chris , Naliboff Bruce D. , Pontari Michel A. , Rodríguez Larissa V. , Schaeffer Anthony J. , Schrepf Andrew , Stephens-Shields Alisa , Sutcliffe Siobhan , Taple Bayley J. , Williams David A. , Landis J. Richard
Published: November 2024

Pain clinical trials are notoriously complex and often inefficient in demonstrating efficacy, even for known efficacious treatments. A major issue is the difficulty in the a priori identification of specific phenotypes to include in the study population. Recent work has identified the extent of widespread pain as an important determinant of the likelihood of response to therapy, but it has not been tested in clinical trials for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). We explored this hypothesis using data from 3 previously published trials testing treatments for IC/BPS, which suggested modest benefits but did not meet a priori primary outcome statistical significance criteria. Importantly, these studies also collected symptom questionnaire data that allowed us to retrospectively identify participants with and without widespread pain. Analyzing the treatment by the degree of widespread pain revealed a difference in outcome and statistical significance level for each trial. Participants with predominately local pain (ie, limited widespread pain symptoms) responded to therapy targeting local symptoms, whereas those with widespread pain did not. Alternatively, participants with widespread pain beyond their local pelvic pain responded to more centrally acting treatments. Our results suggest that differentiating patients based on widespread vs more localized pain is a key consideration for designing future clinical trials for conditions with variable pain profiles, such as IC/BPS and potentially other pain-based syndromic disorders.
Childhood maltreatment and chronic “all over” body pain in adulthood: a counterfactual analysis using UK Biobank
Authors: Timmins Kate A. , Hales Tim G. , Macfarlane Gary J. ,   on behalf of the Consortium Against Pain InEquality (CAPE) investigators and Chronic Pain Advisory Group
Published: November 2024

Evidence linking adverse childhood experiences and chronic pain in adulthood is largely cross-sectional, potentially subject to recall bias and does not allow exploration of mediating pathways. We analysed a large population-based cohort (UK Biobank) using a causal framework, to determine if childhood maltreatment is related to chronic “all over” body pain in adulthood. We used doubly robust estimation with inverse probability weights to estimate the difference in risk of chronic pain “all over” between those exposed/not exposed to childhood maltreatment (abuse or neglect). In addition, we looked at interaction with adult stressful life events and examined mediation using inverse odds weighting in a generalized linear model. Using cases with complete data (n = 118,347), the risk of chronic “all over” body pain was higher in the exposed (6.3%, 95% confidence interval [CI] 6.0%-6.5%) than in the unexposed (4.0%; 95% CI 3.8%-4.2%). This difference remained in analyses stratified by sex. Conversely, when analyses were repeated with a negative control exposure, childhood sunburn, risk differences were 0.8% in women (95% CI 0.3%-1.3%) and 0.5% in men (95% CI 0.1%-0.9%). Childhood maltreatment and adult life events had similar effects, and there was a supra-additive risk (1.2%; 95% CI 0.6-1.7) when experiencing both. In mediation analyses, the total effect was a relative risk of 1.57 (95% CI 1.49-1.66), while the estimated indirect effect via all mediators was relative risk 1.16 (95% CI 1.14-1.18). Reducing childhood maltreatment would likely prevent cases of chronic widespread pain in adulthood. Stressful adult events and mediators may offer opportunities for intervention.
Evolving indications and management patterns in heart – kidney transplantation
Authors: Lang Frederick M. , Topkara Veli K.
Published: November 2024

Purpose of review

Dual heart–kidney transplantation (HKT) is an increasingly utilized option for patients with end-stage heart failure and impaired renal function. In 2023, the United Network for Organ Sharing (UNOS) formalized indications for simultaneous heart–kidney transplantation (SHKT) and kidney-after-heart transplantation (KAHT). In light of this landmark effort, we review the evolution in HKT indications, outcomes after SHKT and KAHT in various patient populations, novel considerations in pre and posttransplant management, and areas for future research.

Recent findings

The UNOS policy was borne out of retrospective outcome studies suggesting that SHKT is superior to single-organ heart transplantation (HT) in select patients with sufficiently severe renal impairment. KAHT utilization continues to evolve, providing a helpful safety net for HT recipients with irreversible worsening of renal function. Time-limited pretransplant device trials are useful for identifying optimal candidates for HKT, and calcineurin inhibitor-sparing regimens can preserve posttransplant renal function. Explorations into artificial intelligence algorithms and biomarker technology represent interesting future opportunities.

Recent studies have refined selection and management of dual HKT recipients. The new UNOS policies now provide helpful standardization to the field. Rapid innovation to date has made dual HKT an exciting therapeutic strategy for patients with few options left.
Prehospital Restraint Use in Pediatric Patients With Mental and Behavioral Health Emergencies
Authors: Cummings Caroline , Babcock Lynn , Zhang Yin , Lee Sang Hoon , Schwartz Hamilton , Semenova Olga , Pomerantz Wendy J. ,   the Cincinnati Children's Prehospital Care Committee
Published: November 2024

Objectives

The aims of the study are to characterize children with mental and behavioral health conditions (MBH) transported by emergency medical services (EMS) and examine differences in patient, emergency department (ED), and EMS transport characteristics based on restraint interventions during EMS transport.

Methods

This is a retrospective cohort study of EMS patients with MBH crises, aged 5–18, transported to 2 pediatric EDs over 9 years. Demographic and ED data were collected electronically; EMS data were extracted manually from prehospital care records. Field interventions studied included pharmacologic and mechanical restraints by EMS clinicians. Univariate analysis compared variables between patients who received EMS restraints and those who did not and multivariable logistic regression identified patient factors independently associated with EMS restraint use.

Results

Among 10,264 patients transported by EMS for MBH crises, 1400 encounters were randomly selected, with 768 records available. EMS restraint interventions were used in 73 (9.5%) patients: 5 (0.7%) received only pharmacologic restraints, 58 (7.6%) received only physical restraints, and 10 (1.3%) received both. Those who received EMS restraints were more likely to be younger (35.6% vs 19.6%, P = 0.001), male (71.2% vs 44.6%, P < 0.0001), and had longer scene times (13 vs 9 min). Restraint use was more common when patients were picked up from schools (30.1% vs 14.8%, P = 0.007). EMS-restrained patients were also more likely to receive physical (12.3% vs 2.3%, P < 0.0001), mechanical (15.1% vs 1.0%, P < 0.0001), or pharmacologic (24.7% vs 3.9%, P < 0.0001) restraints in the ED. Predictors of EMS restraint use were male sex (odds ratio, 3.00; 95% confidence interval, 1.74–5.17) and being picked up from schools (odds ratio, 2.08; 95% confidence interval, 1.13–3.81), whereas age group, race, and insurance type were not independent predictors.

Conclusions

Nearly 1 in 10 pediatric patients experiencing mental health crises and transported by EMS required restraint interventions in the field. Male patients, younger aged children, and those picked up from school represent a distinct and vulnerable population that could benefit from specialized prehospital care to manage agitation.
Respiratory Vaccination Rates in People Living With Spinal Cord Injury/Disorder in Switzerland
Authors: Mueller Gabi , Eriks-Hoogland Inge , Hund-Georgiadis Margret , Jordan Xavier , Schubert Martin , Bertschy Sue , Wenk Christian , Brinkhof Martin WG
Published: November 2024

Objective

The aim of the study is to provide a population-based evaluation of vaccination coverage to prevent respiratory complications from SARS-COV-2, influenza, and pneumococcus, among community-dwelling persons with spinal cord injury/disease.

Design

This is a cross-sectional survey conducted in 2022, utilizing questionnaires administered to persons with spinal cord injury/disease living in Switzerland. Main outcomes were ever-vaccination rates for SARS-COV-2, influenza, and pneumococcus. Secondary outcomes included demographics, lesion and education levels, as well as respiratory and cardiovascular conditions. Vaccine hesitancy was additionally assessed for all three vaccines in nonvaccinated persons through questions on reasons for not getting vaccinated.

Results

A total of 1158 persons participated in this survey. Overall vaccination rates were highest for SARS-COV-2 86.5% (95% CI = 84.4–88.3), followed by influenza 44.6 (41.7–47.6) and pneumococcus: 7.5% (6.0–9.3). The most prominent reasons for not being vaccinated were doubt on effectiveness (72.7%) and potential side effects (60%) for SARS-COV-2, patients did not feel at risk for influenza (57%) and insufficient information from the physician (52.4%) for pneumococcus vaccination.

Conclusions

In individuals with spinal cord injury/disease, vaccination coverage is notably low for influenza and especially pneumococcus. Vaccine hesitancy varies between vaccination types and is associated with vaccine-specific reasons. These findings underscore the imperative for updated clinical vaccination guidelines, improved public health information, and targeted intervention programs for specific patient groups.
Adherence to Physical Activity Guidelines in Manual Wheelchair Users With Spinal Cord Injury and the Association With Shoulder Pain
Authors: de Vries Wiebe H.K. , Arnet Ursina , Bossuyt Fransiska M. , de Groot Sonja , Eriks-Hoogland Inge , Perret Claudio
Published: November 2024

Objective

The aim of the study is to investigate the association between adherence to spinal cord injury–specific physical activity guidelines in manual wheelchair users with spinal cord injury and shoulder pain prevalence.

Design

This is a cross-sectional analysis of the SwiSCI Community Survey 2022 data, assessing aerobic activity and muscle strength training adherence in manual wheelchair users with spinal cord injury and shoulder pain prevalence. Logistic regression analysis was used to identify the association between meeting the physical activity guidelines and shoulder pain.

Results

Low adherence to aerobic activity and strength training guidelines are observed, with 46% and 64% of the study sample not meeting the respective guidelines. The low adherence to physical activity guidelines contrasts with the general Swiss population from which around 75% is physically active for more than 2.5 hrs a week. Manual wheelchair users present a high prevalence of shoulder pain (40%) and nonadherence to aerobic guidelines in the study sample correlates with 1.55–1.97 higher odds of having shoulder pain.

Conclusions

Aerobic activity adherence is associated with lower shoulder pain prevalence, emphasizing its potential for injury prevention. Overall, the presented findings necessitate further longitudinal studies and interventions for a comprehensive understanding and effective management of shoulder pain in manual wheelchair users with spinal cord injury.
Labor Market Participation of Persons With Spinal Cord Injury Living in Switzerland Between 2012 and 2022
Authors: Schwegler Urban , Galvis Aparicio Mayra , Staubli Stefan , Austin-Cliff George , Brinkhof Martin W.G.
Published: November 2024

Objectives

The aim of the study is to examine labor market participation of individuals with spinal cord injury living in Switzerland over the past decade and in relation to the general population.

Design

This is a descriptive study, using longitudinal panel data from the 2012, 2017, and 2022 community surveys of the Swiss Spinal Cord Injury Cohort Study and general population data from the Swiss Labor Force Survey.

Results

Employment rates among spinal cord injury responders were 56% in 2012, 61% in 2017, and 64.6% in 2022. Employment gaps between the spinal cord injury and the Swiss general population samples decreased from 22.5% (2012) to 15.4% (2022). This decrease was particularly evident for females, middle-aged individuals, and people with tetraplegia but contrasted with increased employment gaps in Southwestern Switzerland.

Conclusions

By identifying increased employment rates among spinal cord injury responders along with decreased employment gaps in relation to the general population, our study indicates improved opportunities for persons with impairments in the Swiss labor market over the past decade. While there is still room to improve the labor market participation prospects among the Swiss spinal cord injury population, particular efforts at the regional level are required to ensure equal labor market participation opportunities for all individuals with spinal cord injury living in Switzerland.
Medical mistrust and vaccine-hesitant attitudes explain SARS-CoV-2 vaccination disparities in a mixed serostatus cohort
Authors: Friedman M. Reuel , Wingood Gina , Krause Kristen D. , Krier Sarah , D'Souza Gypsyamber , Kempf Mirjam-Colette , Mimiaga Matthew J. , Kwait Jenn , Jones Deborah L. , Martinson Jeremy , Marques Ernesto T. , Tien Phyllis , Anastos Kathryn , Ramirez Catalina , Cohen Mardge , Camacho-Rivera Marlene , Goparaju Lakshmi , Rinaldo Charles R.
Published: November 2024

Objectives:

To understand the extent of racial disparities in SARS-CoV-2 vaccination among PWH and those vulnerable to HIV infection and to estimate the contributions of medical mistrust and vaccine-hesitant attitudes to these disparities.

Design:

Quantitative data analyses in a racially and gender-diverse, mixed-serostatus prospective cohort, the Multicenter AIDS Cohort Study (MACS)/Women's Interagency HIV Study (WIHS) Combined Cohort Study.

Methods:

Interviewer-assisted questionnaires assessed SARS-CoV-2 vaccination, medical mistrust, and vaccine-hesitant attitudes from March 2021 to September 2022 (n = 3948). Longitudinal analyses assessed effects of sociodemographics on medical mistrust and vaccine-hesitant attitudes. A hierarchical multivariable logistic regression assessed effects of these co-factors on SARS-CoV-2 vaccination. Causal mediation models assessed whether medical mistrust mediated the relationship between Black identity and vaccine-hesitant attitudes, and vaccine-hesitant attitudes mediated the relationship between Black identity and SARS-CoV-2 nonvaccination.

Results:

Participants’ mean age was 56.7; 55.3% were Black, 52.6% cisgender female, 62.6% PWH. 10.1% reported never receiving SARS-CoV-2 vaccinations (13.4% of Black and 4.5% of White participants). Black-identified participants had higher odds of nonvaccination than White participants [aOR = 1.72; 95% confidence interval (CI) 1.08–2.72]. Medical mistrust mediated the relationship between Black identity and vaccine-hesitant attitudes, accounting for 46% of the effect (P < 0.0001). Vaccine-hesitant attitudes mediated the relationship between Black identity and SARS-CoV-2 nonvaccination to the extent that 57.7% (95% CI 25.3–90.1%) of the disparity would be eliminated if vaccine-hesitant attitudes among Black respondents were reduced to levels reported among other racial groups.

Conclusion:

Findings indicate a profound need to build trustworthy healthcare environments to combat medical mistrust and vaccine-hesitant attitudes in Black communities in the United States, including those affected by HIV.