bluuebunny/crossref_metadata_2025 huggingface dataset:
A multiresolution method for modelling galaxy and massive black hole mergers
Authors: Attard Kate , Gualandris Alessia , Read Justin I , Dehnen Walter
Published: February 2024

The coalescence of the most massive black hole (MBH) binaries releases gravitational waves (GWs) within the detectable frequency range of pulsar timing arrays (PTAs; 10−9 to 10−6 Hz). The incoherent superposition of GWs from MBH mergers, the stochastic gravitational wave background (GWB), can provide unique information on MBH parameters and the large-scale structure of the Universe. The recent evidence for a GWB reported by the PTAs opens an exciting new window on to MBHs and their host galaxies. However, the astrophysical interpretation of the GWB requires accurate estimations of MBH merger time-scales for a statistically representative sample of galaxy mergers. This is numerically challenging; a high numerical resolution is required to avoid spurious relaxation and stochastic effects, while a large number of simulations are needed to sample a cosmologically representative volume. Here, we present a new multimass modelling method to increase the central resolution of a galaxy model at a fixed particle number. We follow mergers of galaxies hosting central MBHs with the fast multiple method code griffin at two reference resolutions and with two refinement schemes. We show that both refinement schemes are effective at increasing central resolution, reducing spurious relaxation and stochastic effects. A particle number of N ≥ 106 within a radius of five times the sphere of influence of the MBHs is required to reduce numerical scatter in the binary eccentricity and the coalescence time-scale to <30 per cent, a resolution that can only be reached at present with the mass refinement scheme.
A model of solar magnetic flux rope eruption initiated primarily by magnetic reconnection
Authors: Liu Qingjun , Jiang Chaowei , Bian Xinkai , Feng Xueshang , Zuo Pingbing , Wang Yi
Published: February 2024

There is a heated debate regarding the specific roles played by ideal magnetohydrodynamic (MHD) instability and magnetic reconnection in triggering solar eruptions. In the context of a pre-existing magnetic flux rope (MFR) before an eruption, it is widely believed that an ideal MHD instability, in particular, the torus instability, is responsible for triggering and driving the eruption, while reconnection, as invoked in the wake of the erupting MFR, plays a secondary role. Here, we present a new numerical MHD model in which the eruption of a pre-existing MFR is primarily triggered and driven by reconnection. In this model, a stable MFR embedded in a strapping field is set as the initial condition. A surface converging flow is then applied at the lower boundary, pushing magnetic flux towards the main polarity inversion line. It drives a quasi-static evolution of the system, during which a current layer is built up below the MFR with decreasing thickness. Once reconnection starts in the current sheet, the eruption commences, which indicates that the reconnection plays a determining role in triggering the eruption. By further analysing the works done by the magnetic flux of the pre-existing MFR and the newly reconnected flux during the acceleration stage of the eruption, we find that the latter plays a major role in driving the eruption. Such a model may explain observed eruptions in which the pre-eruption MFR has not reached the conditions for ideal instability.
Variety of disc wind-driven explosions in massive rotating stars
Authors: Crosato Menegazzi Ludovica , Fujibayashi Sho , Takahashi Koh , Ishii Ayako
Published: February 2024

We perform a set of two-dimensional, non-relativistic, hydrodynamics simulations for supernova-like explosions associated with stellar core collapse of rotating massive stars into a system of a black hole and a disc connected by the transfer of matter and angular momentum. Our model of the central engine also includes the contribution of the disc wind. This study is carried out using the open-source hydrodynamic code athena++, for which we implement a method to calculate self-gravity for axially symmetric density distributions. We investigate the explosion properties and the 56Ni production of a star with the zero-age main-sequence mass of $M_\mathrm{ZAMS}=20\, M_\odot$ varying some features of the wind injection. We find a large variety of explosion energy with Eexpl ranging from ∼0.049 × 1051 to ∼34 × 1051 erg and ejecta mass Mej from 0.58 to 6 M⊙, which shows a bimodal distribution in high- and low-energy branches. We demonstrate that the resulting outcome of a highly or sub-energetic explosion for a certain stellar structure is mainly determined by the competition between the ram pressure of the injected matter and that of the infalling envelope. In the nucleosynthesis analysis the 56Ni mass produced in our models goes from <0.2 M⊙ in the sub-energetic explosions to 2.1 M⊙ in the highly energetic ones. These results are consistent with the observational data of stripped-envelope and high-energy SNe such as broad-lined Type Ic SNe.
Correcting 4sU induced quantification bias in nucleotide conversion RNA-seq data
Authors: Berg Kevin , Lodha Manivel , Delazer Isabel , Bartosik Karolina , Garcia Yilliam Cruz , Hennig Thomas , Wolf Elmar , Dölken Lars , Lusser Alexandra , Prusty Bhupesh K , Erhard Florian
Published: February 2024

Nucleoside analogues like 4-thiouridine (4sU) are used to metabolically label newly synthesized RNA. Chemical conversion of 4sU before sequencing induces T-to-C mismatches in reads sequenced from labelled RNA, allowing to obtain total and labelled RNA expression profiles from a single sequencing library. Cytotoxicity due to extended periods of labelling or high 4sU concentrations has been described, but the effects of extensive 4sU labelling on expression estimates from nucleotide conversion RNA-seq have not been studied. Here, we performed nucleotide conversion RNA-seq with escalating doses of 4sU with short-term labelling (1h) and over a progressive time course (up to 2h) in different cell lines. With high concentrations or at later time points, expression estimates were biased in an RNA half-life dependent manner. We show that bias arose by a combination of reduced mappability of reads carrying multiple conversions, and a global, unspecific underrepresentation of labelled RNA emerging during library preparation and potentially global reduction of RNA synthesis. We developed a computational tool to rescue unmappable reads, which performed favourably compared to previous read mappers, and a statistical method, which could fully remove remaining bias. All methods developed here are freely available as part of our GRAND-SLAM pipeline and grandR package.
Human NTHL1 expression and subcellular distribution determines cisplatin sensitivity in human lung epithelial and non-small cell lung cancer cells
Authors: Kar Anirban , Degtyareva Natalya P , Doetsch Paul W
Published: February 2024

Base excision repair is critical for maintaining genomic stability and for preventing malignant transformation. NTHL1 is a bifunctional DNA glycosylase/AP lyase that initiates repair of oxidatively damaged pyrimidines. Our recent work established that transient over-expression of NTHL1 leads to acquisition of several hallmarks of cancer in non-tumorigenic immortalized cells likely through interaction with nucleotide excision repair protein XPG. Here, we investigate how NTHL1 expression levels impact cellular sensitivity to cisplatin in non-tumorigenic immortalized cells and five non-small cell lung carcinomas cell lines. The cell line with lowest expression of NTHL1 (H522) shows the highest resistance to cisplatin indicating that decrease in NTHL1 levels may modulate resistance to crosslinking agents in NSCLC tumors. In a complementation study, overexpression of NTHL1 in H522 cell line sensitized it to cisplatin. Using NTHL1 N-terminal deletion mutants defective in nuclear localization we show that cisplatin treatment can alter NTHL1 subcellular localization possibly leading to altered protein-protein interactions and affecting cisplatin sensitivity. Experiments presented in this study reveal a previously unknown link between NTHL1 expression levels and cisplatin sensitivity of NSCLC tumor cells. These findings provide an opportunity to understand how altered NTHL1 expression levels and subcellular distribution can impact cisplatin sensitivity in NSCLC tumor cells.
An Erdős–Kac theorem for integers with dense divisors
Authors: Tenenbaum Gérald , Weingartner Andreas
Published: February 2024

We show that for large integers n, whose ratios of consecutive divisors are bound above by an arbitrary constant, the number of prime factors follows an approximate normal distribution, with mean $C \log_2 n$ and variance $V \log_2 n$, where $C=1/(1-{\rm e}^{-\gamma})\approx 2.280$ and V ≈ 0.414. This result is then generalized in two different directions.
Views and opinions of farmers and consumers on the trajectory of agriculture in times of military conflict: Insights from a Q-study in Germany
Authors: Noack Marlene E , Tietjens Florian , Latacz-Lohmann Uwe
Published: February 2024

After three decades of orienting agriculture towards ecological and social sustainability goals, the Ukraine war catapulted productivity and supply goals back onto the political agenda. Against this background, the present study aimed to establish how farmers and food consumers envision the future of agriculture. Application of Q-methodology revealed three opinion groups for both farmers and consumers. In conclusion, the Ukraine war has not significantly shifted the balance between old and new societal demands on agriculture. Old discrepancies in the views of farmers and the non-farming population persist. While among the farmers surveyed the group of those who adhere to ‘business as usual’ predominates, there is no group among the consumers surveyed who share this view. Rather, there is a majority desire among consumers for the sector to continue to be aligned with sustainability goals. Security of supply is only an issue for a small proportion of the consumers surveyed.
News from the United Nations Commission on International Trade Law (UNCITRAL): the work of the fifty-sixth commission session
Authors: Mostad-Jensen Anne
Published: February 2024

The United Nations Commission on International Trade Law (UNCITRAL) is the core legal body of the United Nations system in the field of international trade law. It has been carrying out its mandate to further the progressive harmonization and unification of international trade law since 1966. This article provides an overview of the fifty-sixth session of UNCITRAL and the activities of its working groups and Secretariat since its last session.
A New Multiplex TaqMan qPCR for Precise Detection and Quantification of Clavibacter michiganensis in Seeds and Plant Tissue
Authors: Brochu Anne-Sophie , Dumonceaux Tim J. , Valenzuela Miryam , Bélanger Richard , Pérez-López Edel
Published: February 2024

Bacterial canker of tomato caused by Clavibacter michiganensis (Cm) is one of the most devastating bacterial diseases affecting the tomato industry worldwide. As the result of Cm colonization of the xylem, the susceptible host shows typical symptoms of wilt, marginal leaf necrosis, stem cankers, and ultimately plant death. However, what makes Cm an even more dangerous pathogen is its ability to infect seeds and plants without causing symptoms. Unfortunately, there are no resistant cultivars or effective chemical or biological control methods available to growers against Cm. Its control relies heavily on prevention. The implementation of a rapid and accurate detection tool is imperative to monitor the presence of Cm and prevent its spread. In this study, we developed a specific and sensitive multiplex TaqMan qPCR assay to detect Cm and distinguish it from related bacterial species that affect tomato plants. Two Cm chromosomal virulence-related genes, rhuM and tomA, were used as specific targets. The plant internal control tubulin alpha-3 was included in each of the multiplexes to improve the reliability of the assay. Specificity was evaluated with 37 bacterial strains including other Clavibacter spp. and related and unrelated bacterial pathogens from different geographic locations affecting a wide variety of hosts. Results showed that the assay is able to discriminate Cm strains from other related bacteria. The assay was validated on tissue and seed samples following artificial infection, and all tested samples accurately detected the presence of Cm. The tool described here is highly specific, sensitive, and reliable for the detection of Cm and allows the quantification of Cm in seeds, roots, stems, and leaves. The diagnostic assay can also be adapted for multiple purposes such as seed certification programs, surveillance, biosafety, the effectiveness of control methods, border protection, and epidemiological studies.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Real-Time Machine Learning Alerts to Prevent Escalation of Care: A Nonrandomized Clustered Pragmatic Clinical Trial*
Authors: Levin Matthew A. , Kia Arash , Timsina Prem , Cheng Fu-yuan , Nguyen Kim-Anh-Nhi , Kohli-Seth Roopa , Lin Hung-Mo , Ouyang Yuxia , Freeman Robert , Reich David L.
Published: February 2024

OBJECTIVES:

Machine learning algorithms can outperform older methods in predicting clinical deterioration, but rigorous prospective data on their real-world efficacy are limited. We hypothesized that real-time machine learning generated alerts sent directly to front-line providers would reduce escalations.

DESIGN:

Single-center prospective pragmatic nonrandomized clustered clinical trial.

SETTING:

Academic tertiary care medical center.

PATIENTS:

Adult patients admitted to four medical-surgical units. Assignment to intervention or control arms was determined by initial unit admission.

INTERVENTIONS:

Real-time alerts stratified according to predicted likelihood of deterioration sent either to the primary team or directly to the rapid response team (RRT). Clinical care and interventions were at the providers’ discretion. For the control units, alerts were generated but not sent, and standard RRT activation criteria were used.

MEASUREMENTS AND MAIN RESULTS:

The primary outcome was the rate of escalation per 1000 patient bed days. Secondary outcomes included the frequency of orders for fluids, medications, and diagnostic tests, and combined in-hospital and 30-day mortality. Propensity score modeling with stabilized inverse probability of treatment weight (IPTW) was used to account for differences between groups. Data from 2740 patients enrolled between July 2019 and March 2020 were analyzed (1488 intervention, 1252 control). Average age was 66.3 years and 1428 participants (52%) were female. The rate of escalation was 12.3 vs. 11.3 per 1000 patient bed days (difference, 1.0; 95% CI, –2.8 to 4.7) and IPTW adjusted incidence rate ratio 1.43 (95% CI, 1.16–1.78; p < 0.001). Patients in the intervention group were more likely to receive cardiovascular medication orders (16.1% vs. 11.3%; 4.7%; 95% CI, 2.1–7.4%) and IPTW adjusted relative risk (RR) (1.74; 95% CI, 1.39–2.18; p < 0.001). Combined in-hospital and 30-day-mortality was lower in the intervention group (7% vs. 9.3%; –2.4%; 95% CI, –4.5% to –0.2%) and IPTW adjusted RR (0.76; 95% CI, 0.58–0.99; p = 0.045).

CONCLUSIONS:

Real-time machine learning alerts do not reduce the rate of escalation but may reduce mortality.
Impending HCC diagnosis in patients with cirrhosis after HCV cure features a natural killer cell signature
Authors: Engelskircher Sophie Anna , Chen Po-Chun , Strunz Benedikt , Oltmanns Carlos , Ristic Tijana , Owusu Sekyere Solomon , Kraft Anke R.M. , Cornberg Markus , Wirth Thomas , Heinrich Bernd , Björkström Niklas K. , Wedemeyer Heiner , Woller Norman
Published: February 2024

Background and Aims:

The risk of developing HCC in chronically infected patients with AQ2 HCV with liver cirrhosis is significantly elevated. This risk remains high even after a sustained virological response with direct-acting antivirals. To date, disease-associated signatures of NK cells indicating HCC development are unclear.

Approach and Results:

This study investigated NK cell signatures and functions in 8 cohorts covering the time span of HCC development, diagnosis, and onset. In-depth analysis of NK cell profiles from patients with cirrhosis who developed HCC (HCV-HCC) after sustained virological response compared with those who remained tumor-free (HCV-noHCC) revealed increasingly dissimilar NK cell signatures over time. We identified expression patterns with persistently high frequencies of TIM-3 and CD38 on NK cells that were largely absent in healthy controls and were associated with a high probability of HCC development. Functional assays revealed that the NK cells had potent cytotoxic features. In contrast to HCV-HCC, the signature of HCV-noHCC converged with the signature found in healthy controls over time. Regarding tissue distribution, single-cell sequencing showed high frequencies of these cells in liver tissue and the invasive margin but markedly lower frequencies in tumors

Conclusions:

We show that HCV-related HCC development has profound effects on the imprint of NK cells. Persistent co-expression of TIM-3hi and CD38+ on NK cells is an early indicator for HCV-related HCC development. We propose that the profiling of NK cells may be a rapid and valuable tool to assess the risk of HCC development in a timely manner in patients with cirrhosis after HCV cure.
Dose Measurements at Provision Proton Therapy Center
Authors: Burahmah Naser , Heilbronn Lawrence
Published: February 2024

Proton therapy is an advanced method for treating cancerous tumors, and its adoption has expanded significantly in recent years. The production of high-energy protons, however, may result in the creation of secondary neutrons and gamma rays. Hence, ensuring radiation safety at proton therapy centers is crucial, with shielding playing a vital role. This study aimed to evaluate the efficacy of the shielding implemented at the Provision Proton Therapy center in Knoxville, TN, USA. For this purpose, we measured and compared gamma ray radiation levels within the treatment room and the facility’s roof. These measurements were conducted using a NaI(Tl) scintillator detector. The PHITS Monte Carlo code was used to deconvolute the incident spectrum using detector response functions. Findings reveal that the facility’s shielding effectively protects the general public from gamma ray radiation, with the effective dose within the treatment room being minimal and dose on the roof was comparable to background radiation levels. However, it is important to note that this study did not address the issue of secondary neutron radiation field, which is an important aspect of dose and radiation safety in proton therapy centers.
A Review of the Resuspension of Radioactively Contaminated Particles by Vehicle and Pedestrian Traffic—Current Theory, Practice, Gaps, and Needs
Authors: Kaminski Michael D. , Daiyega Nico , Magnuson Matthew
Published: February 2024

The resuspension of radioactively contaminated particles in a built environment, such as from urban surfaces like foliage, building exteriors, and roadways, is described empirically by current plume and dosimetry models used for hazard assessment and long-term risk purposes. When applying these models to radiological contamination emergencies affecting urban areas, the accuracy of the results for recent contamination deposition is impacted in two main ways. First, the data supporting the underlying resuspension equations was acquired for open, quiescent conditions with no vehicle traffic or human activities, so it is not necessarily representative of the urban environment. Second, mechanical disturbance by winds in urban canyons and during emergency operations caused by vehicle traffic and human activities are not directly considered by the equations. Accordingly, plume and dosimetry models allow the user to input certain compensating values, but the models do not necessarily supply users instructions on what values to use. This manuscript reviews the available literature to comprehensively and consistently pool data for resuspension due to mechanically induced resuspension applicable to urban contamination. Because there are few studies that directly measured radioactive resuspension due to vehicles and pedestrians, this review novelly draws on a range of other studies involving non-radioactive particles, ranging from outdoor air pollution emissions to indoor allergen transport. The results lead to tabulated, recommended values for specific conditions in the emergency phase to help users of plume and dosimetry models maintain the conservativeness needed to properly capture the potential radiation dose posed by mechanically induced resuspension. These values are of benefit to model users until better data are available. The results also suggest the types of data that may result in improved plume and dose modeling.
Evaluation of the German Version of the Keratoconus Outcomes Research Questionnaire
Authors: Pomberger Leon , Tasch Lisa , Lundström Mats , Waser Klemens , Khalil Haidar , Kronschläger Martin , Hirnschall Nino , Bolz Matthias
Published: February 2024

Purpose:

To translate, validate, and evaluate the psychometric properties of the German version of Keratoconus Outcomes Research Questionnaire (KORQ).

Methods:

This prospective study included 3 phases. In phase 1, the KORQ was translated in a standardized way; in phase 2, Rasch validation was performed; in phase 3, the validated questionnaire was evaluated in a separate patient cohort. All patients answered the German KORQ. Scheimpflug imaging (Pentacam) and optical coherence tomography scans (MS-39) were conducted. Corneal imaging measurements were correlated with patient-reported outcome measures.

Results:

After standardized translation, 100 patients self-administered the German KORQ. Rasch analysis was conducted for psychometric testing of the KORQ. Based on the results of the Rasch analysis, the original German version of the KORQ was modified and any items showing a misfit were excluded. This resulted in a new shortened version of the KORQ, which was evaluated in 30 patients. The revised German KORQ met the criteria of Rasch analysis and showed excellent internal consistency reliability and convergent validity. The correlation between the KORQ score and various clinical measurements was examined using Spearman correlation. A significant moderate correlation was observed between the D (r = 0.237; P = 0.006) and Kmax (r = 0.162; P = 0.065) values of Pentacam. Inverse correlations were observed for thinnest pachymetry measured with MS-39 (r = −0.167; P = 0.058) and best corrected visual acuity (r = −0.210; P = 0.016).

Conclusions:

The shortened German KORQ met the assumptions of the Rasch model and displayed satisfactory psychometric properties. The German KORQ could be adopted as a powerful patient-reported outcome measures tool for German-speaking patients with keratoconus in the future.
Pulmonary Complications of Cytomegalovirus Infection in Neonates and Infants: A Systematic Review of Case Reports and Pooled Analysis
Authors: Ong Leong Tung , Fan Si Wei David
Published: February 2024

Background:

Cytomegalovirus (CMV) causes intrauterine infections in 0.67% of neonates, with 12.7% displaying symptoms at birth. CMV can lead to severe multiorgan involvement, and mortality in symptomatic cases is around 30%. Pulmonary complications are rare in infants with CMV. This review assesses pulmonary complications and outcomes in infants with CMV infection.

Methods:

A systematic literature search was conducted using PubMed, SCOPUS and Ovid SP to retrieve case reports on pulmonary complications in infants with congenital or perinatal CMV infection. Descriptive analysis and pooled analysis were conducted for the case reports.

Results:

A total of 28 articles with 38 patients were included in this systematic review. The reported pulmonary complications in the case reports were CMV pneumonitis (34.2%), persistent pulmonary hypertension of the newborn (18.4%), emphysema and chronic lung disease (15.8%), diaphragmatic dysfunction (13.2%), lung cysts and calcifications (10.5%), Pneumocystis jirovecii infection (7.9%), pulmonary hypoplasia (5.3%) and bronchial atresia (2.6%). Seven (18.4%) of 38 patients passed away because of the pulmonary complications of CMV infection. Congenital transmission (P = 0.0108), maternal CMV (P = 0.0396) and presence of neonatal comorbidities (P = 0.0398) were independent risk factors for mortality.

Conclusions:

This systematic review demonstrated infrequent occurrence of severe pulmonary involvement in CMV infection but should be considered in infants with persistent or severe respiratory symptoms.
Vaccine Associated Measles Complicated by Suspected Measles Inclusion Body Encephalitis in a Pediatric Leukemia Patient and Stem Cell Transplant Recipient: A Focus on Clinical Evolution and Management
Authors: Kushner Lauren E. , Kamens Jennifer , Bertaina Alice , Shyr David , Gans Hayley A.
Published: February 2024

Background:

Immunocompromised individuals are at increased risk for severe disease and complications from viral infections, highlighting the importance of vaccination. However, in extremely rare situations, vaccine associated viral infections can be associated with disseminated disease and complications in immunocompromised hosts.

Case:

Herein, we present a case of a 1-year-old child diagnosed with acute myeloid leukemia less than 2 weeks after receiving live viral vaccines who developed acute vaccine-strain measles virus disease, later complicated by central nervous system involvement following hematopoietic stem cell transplantation. A brain biopsy specimen was positive for vaccine-strain measles virus detected by reverse transcriptase polymerase chain reaction.

Management and Outcome:

She was treated with intravenous ribavirin, inosine pranobex, intrathecal interferon-alpha and donor lymphocyte infusion following measles-mumps-rubella vaccine boost. Despite these measures, the patient suffered neurologic decline and dysautonomia, expiring after compassionate extubation. Management and ideal risk mitigation strategies are discussed within the context of existing literature for this rare complication.
Quantitative sensory testing, psychological factors, and quality of life as predictors of current and future pain in patients with knee osteoarthritis
Authors: Hertel Emma , Arendt-Nielsen Lars , Olesen Anne Estrup , Andersen Michael Skipper , Petersen Kristian Kjær-Staal
Published: February 2024

Substantial interindividual variability characterizes osteoarthritis (OA) pain. Previous findings identify quantitative sensory testing (QST), psychological factors, and health-related quality of life as contributors to OA pain and predictors of treatment outcomes. This exploratory study aimed to explain baseline OA pain intensity and predict OA pain after administration of a nonsteroidal anti-inflammatory drug in combination with paracetamol for 3 weeks. The Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score was used to estimate OA pain presentation. One hundred one patients were assessed at baseline and follow-up using QST (pressure pain thresholds and temporal summation of pain [TSP]), symptoms of depression and anxiety, pain catastrophizing scales (PCSs), and health-related quality of life. Linear regression with backward selection identified that PCS significantly explained 34.2% of the variability in baseline KOOS pain, with nonsignificant contributions from TSP. Pain catastrophizing score and TSP predicted 29.3% of follow-up KOOS pain, with nonsignificant contributions from symptoms of anxiety. When assessed separately, PCS was the strongest predictor (32.2% of baseline and 24.1% of follow-up pain), but QST, symptoms of anxiety and depression, PCS, and quality of life also explained some variability in baseline and follow-up knee OA pain. Further analyses revealed that only TSP and PCS were not mediated by any other included variables, highlighting their role as unique contributors to OA pain presentation. This study emphasizes the importance of embracing a multimodal approach to OA pain and highlights PCS and TSP as major contributors to the baseline OA pain experience and the OA pain experience after OA treatment.
Immune-related signature identifies IL1R2 as an immunological and prognostic biomarker in pancreatic cancer
Authors: Wang Chengcheng , Chen Yuan , Yin Xinpeng , Xu Ruiyuan , Ruze Rexiati , Song Jianlu , Hu Chenglin , Zhao Yupei
Published: February 2024

Objective:

Pancreatic cancer is one of the most aggressive malignancies, a robust prognostic signature and novel biomarkers are urgently needed for accurate stratification of the patients and optimization of clinical decision-making.

Methods:

A list of bioinformatic analysis were applied in public dataset to construct an immune-related signature. Furthermore, the most pivotal gene in the signature was identified. The potential mechanism of the core gene function was revealed through GSEA, CIBERSORT, ESTIMATE, immunophenoscore (IPS) algorithm, single-cell analysis, and functional experiment.

Results:

An immune-related prognostic signature and associated nomogram were constructed and validated. Among the genes constituting the signature, interleukin 1 receptor type II (IL1R2) was identified as the gene occupying the most paramount position in the risk signature. Meanwhile, knockdown of IL1R2 significantly inhibited the proliferation, invasion, and migration ability of pancreatic cancer cells. Additionally, high IL1R2 expression was associated with reduced CD8+ T cell infiltration in pancreatic cancer microenvironment, which may be due to high programmed cell death-ligand-1 (PD-L1) expression in cancer cells. Finally, the IPS algorithm proved that patients with high IL1R2 expression possessed a higher tumor mutation burden and a higher probability of benefiting from immunotherapy.

Conclusion:

In conclusion, our study constructed an efficient immune-related prognostic signature and identified the key role of IL1R2 in the development of pancreatic cancer, as well as its potential to serve as a biomarker for immunotherapy efficacy prediction for pancreatic cancer.
Evaluation of a Radiological Tool for Semiautomatic Scalar Translocation Detection After Cochlear Implantation
Authors: Arends Sebastiaan R.S. , Briaire Jeroen J. , Geiger Stephan , Nauwelaers Tim , Frijns Johan H.M.
Published: February 2024

Objective

To evaluate the clinical applicability of a semiautomatic radiological tool for scalar translocation detection.

Study Design

Retrospective study.

Setting

Tertiary care academic center.

Patients

We included 104 patients implanted with 116 HiFocus Mid-Scala electrode arrays between January 2013 and September 2016.

Intervention

Cochlear implantation.

Main Outcome Measures

The tool's scalar position assessments were compared with manual ones by calculating intraclass coefficient (ICC) for individual contacts and sensitivity and specificity for translocation detection of the whole array. In addition, ICC was calculated for diameters A and B, ratio A/B, and angular insertion depth (AID).

Results

Nine-one percent of cases could be processed, which took 5 to 10 minutes per case. Comparison of manual and semiautomatic scalar position showed for individual contacts an ICC of 0.89 and for the whole array a sensitivity of 97% and a specificity of 96%. ICCs for A, B, and A/B were 0.82, 0.74, and 0.39 respectively. For AID, ICC of each of the 16 contacts was 0.95 or higher.

Conclusions

The semiautomatic radiological tool could analyze most cases and showed good to excellent agreement with manual assessments for translocation detection, diameter A, diameter B, and AID. The variability between semiautomatic and manual measurements is comparable to interobserver variability, indicating that clinical implementation of the tool is feasible.
Treatment of primary vaginal malignant melanoma and review of previous literature: A case report
Authors: Bai Suning , Wu Qi , Song Liyun , Wu Wenfei
Published: February 2024

Introduction:

Primary vaginal malignant melanoma is a rare gynecological malignant tumor with high malignancy and poor prognosis. Because of its insidious incidence, it is generally diagnosed in the late stage, and the 5-year survival rate is only 5% to 25%. Due to the rarity of this disease and the limited number of related cases reported in the literature, there is currently no unified standard for its diagnosis and treatment. Therefore, the treatment of this disease has always been a difficult problem in clinical practice.

Patient concerns:

A 56-year-old woman was admitted to our hospital with discomfort in the lower abdomen.

Diagnosis:

The final diagnosis of this patient was vaginal malignant melanoma (T4N1M0).

Interventions:

The patient underwent extensive hysterectomy, bilateral adnexectomy, pelvic lymph node resection, and total vaginectomy. Following the surgery, the patient received adjuvant chemotherapy.

Outcomes:

The patient was followed up regularly. No recurrence or metastasis has been reported to date.

Conclusion:

The treatment of primary vaginal malignant melanoma is still dominated by surgery, while radiotherapy and chemotherapy are controversial. Immunotherapy and targeted therapy highlight certain advantages in advanced patients, which still need to be verified by large sample studies, We provide a case of postoperative adjuvant chemotherapy for vaginal malignant melanoma. So far, no signs of disease recurrence have been found. As the price of chemotherapy drugs decreases, it is economically convenient and acceptable for most patients, but its effectiveness needs to be observed in large-scale clinical trials.
A multicenter case-control study on postoperative intestinal fistula in Chinese patients with Crohn disease
Authors: Zhongcheng Liu , Qingfan Yang , Xiuling Fu , Meichun Long , Bo Peng , Zhiming Xiao , Qin Guo
Published: February 2024

The aim of this study was to (1) assess the independent factors affecting patients with postoperative intestinal fistula from Crohn disease (CD) by analyzing preoperative clinical data, (2) establish a nomogram prediction model for this condition based on these factors, and (3) validate this model and evaluate its accuracy. In this retrospective multicenter case-control study, the clinical data of 240 patients with CD admitted for surgical treatment between September 2019 and September 2021 at 3 centers were collected. Patients were randomly divided into a training set (168 patients) and a validation set (72 patients). Univariate analysis was performed for relevant factors, and statistically significant factors were then analyzed using multivariate logistic regression to determine the independent influencing factors. A nomogram model for predicting postoperative intestinal fistula in patients with CD was constructed and the accuracy of the model was evaluated using calibration curves. Univariate analysis showed that disease behavior, abdominal abscess, intestinal perforation, neutrophil-to-lymphocyte ratio, systemic immunoinflammatory index, and prognostic nutrition index were factors affecting postoperative intestinal fistula in patients with CD. Multivariate logistic regression analysis showed that neutrophil-to-lymphocyte ratio, prognostic nutrition index, disease behavior, and Crohn disease activity index score were independent influencing factors. After assessing the validation set, the area under the curve was 0.899, indicating good predictive accuracy of the nomogram model. The prediction model developed in this study can effectively predict the risk of postoperative intestinal fistula.
Association between swallowing disorder and prevertebral hyperintensity on magnetic resonance imaging in patients after cervical cord injury without major fracture
Authors: Kumagai Gentaro , Wada Kanichiro , Asari Toru , Nitobe Yohshiro , Takeda On , Fujita Ayaka , Tsuda Eiichi , Ishibashi Yasuyuki
Published: February 2024

This study aimed to clarify the association between swallowing disorder and prevertebral hyperintensity on magnetic resonance imaging (MRI) in patients with cervical spinal cord injury (CSCI) without a major fracture. This retrospective observational study included 30 patients who were diagnosed with acute CSCI without a major fracture (mean age: 69.3 years, 27 men). Swallowing disorder was defined as tube-dependent nutrition because of obvious aspiration 28 days after injury. The high-intensity area (HIA) and anteroposterior width (HIW) of the prevertebral space at C1–7 levels were measured using MRI short-TI inversion recovery midsagittal images. Receiver operating characteristic curve analysis was used to determine the optimal cutoff values of the HIA for predicting swallowing disorder. The incidence of swallowing disorder after CSCI was 16.7%. The HIA was significantly higher in the swallowing disorder group (median, 409.0 mm2) than in the non- swallowing disorder group (median, 159.1 mm2) (P = .04). There was no significant difference in HIW between the two groups. The optimal cutoff point of the HIA was measured at 203.2 mm2 with 80.0% and 20.0% sensitivity and specificity, respectively, with an area under the curve of 0.848 (95% confidence interval, 0.657–1.000, P = .01). The prevertebral hyperintensity area on MRI for swallowing disorder in patients after cervical cord injury without skeletal injury is associated with swallowing disorder. The optimal cutoff point of the area was determined to be 203.2 mm2.
Acute endocarditis complicated by left ventricular pseudoaneurysm with acute bloody pericardial effusion: A case report
Authors: Shimada Akie , Yamamoto Taira , Dohi Shizuyuki , Yokoyama Yasutaka , Endo Daisuke , Tabata Minoru
Published: February 2024

Rationale:

Delay in seeking medical attention for high fever and inadequate diagnosis can lead to rapid progression of inflammation and spread to surrounding tissues and organs. Staphylococcus aureus is a common cause of systemic infections, and infectious endocarditis can swiftly become severe; therefore, careful management is required.

Patient concerns:

A 54-year-old woman was admitted to our hospital with high fever and progressive loss of consciousness. Meningitis was suspected, and antibiotic treatment was initiated. Blood culture revealed methicillin-sensitive Staphylococcus aureus. Subsequently, the patient developed hypotension, bradycardia, and cardiac arrest and underwent emergency cardiopulmonary resuscitation.

Diagnoses:

Transesophageal echocardiography performed during the procedure revealed significant vegetation at the posterior leaflet of the mitral valve, an abscess at the valve annulus, and a pseudoaneurysm of the left ventricular posterior wall.

Interventions:

The patient underwent emergency small incision pericardiotomy drainage, and her blood pressure and heart rate stabilized. After pericardial drainage, acute renal failure, fulminant hepatitis, and disruption of coagulation function were observed, and she was treated with plasma exchange therapy and intravenous immunoglobulin. Resection of the huge vegetation, debridement, patch closure of the ventricular perforation, and mitral valve replacement were performed.

Outcomes:

Surgical findings showed massive vegetation in the posterior leaflet of the mitral valve, an annular abscess in the posterior leaflet of the mitral valve connected to the left ventricular posterior wall, and a pseudoaneurysm. Postoperatively, her pseudoaneurysm resolved and her cardiac function stabilized, while circulatory failure due to bacteremia progressed, and she gradually developed acidosis and unstable blood pressure. Plasma exchange and continuous hemodiafiltration were continued; however, she died of progressive multiorgan failure.

Lesson:

Staphylococcus aureus bacteremia can cause fatal complications. Even when symptoms of meningitis are suspected, it is essential to examine the patient for endocarditis. Delayed diagnosis can lead to fatal endocarditis-related complications.
Surgical treatment of male breast cancer metastasis to thoracic spine: A case report
Authors: Ko Jong-Hyun , Kim Jong-Hong , Ham Dong-Hun
Published: February 2024

Purpose:

We present a rare clinical case of a metastatic spinal tumor in the 7th thoracic spine from male breast cancer (MBC).

Method:

A 62-year-old man was referred as an outpatient, complaining of continuous pain in the back and right flank that began 2 weeks earlier. The patient had no neurologic signs or symptoms but had a medical history of left breast modified radical mastectomy because of MBC. Computed tomography and magnetic resonance imaging showed metastasis in the T7 vertebra and no other metastasis on positron emission tomography/computed tomography or bone scan. Separation surgery was performed with posterior corpectomy of T7 (en bloc excision), followed by stabilization with an expandable titanium cage and pedicle screws. The pathological examination of the excised T7 vertebra confirmed metastatic carcinoma with neuroendocrine differentiation from the breast. Adjuvant chemo-radiotherapy was performed after surgery.

Results:

The patient had no symptoms at the 21-month follow-up. Radiologic studies showed no evidence of recurrent or metastatic lesions.

Conclusion:

MBC is extremely rare, with fewer cases of spinal metastases. Among these, patients who undergo separation surgery are even rarer. This case shows that radical surgery can be an option for MBC with spine metastasis if indicated.
Potential drug targets for myocardial infarction identified through Mendelian randomization analysis and Genetic colocalization
Authors: Wu Jiayu , Fan Qiaoming , He Qi , Zhong Qian , Zhu Xianqiong , Cai Huilian , He Xiaolin , Xu Ying , Huang Yuxuan , Di Xingwei
Published: February 2024

Myocardial infarction (MI) is a major cause of death and disability worldwide, but current treatments are limited by their invasiveness, side effects, and lack of efficacy. Novel drug targets for MI prevention are urgently needed. In this study, we used Mendelian randomization to identify potential therapeutic targets for MI using plasma protein quantitative trait loci as exposure variables and MI as the outcome variable. We further validated our findings using reverse causation analysis, Bayesian co-localization analysis, and external datasets. We also constructed a protein-protein interaction network to explore the relationships between the identified proteins and known MI targets. Our analysis revealed 2 proteins, LPA and APOA5, as potential drug targets for MI, with causal effects on MI risk confirmed by multiple lines of evidence. LPA and APOA5 are involved in lipid metabolism and interact with target proteins of current MI medications. We also found 4 other proteins, IL1RN, FN1, NT5C, and SEMA3C, that may have potential as drug targets but require further confirmation. Our study demonstrates the utility of Mendelian randomization and protein quantitative trait loci in discovering novel drug targets for complex diseases such as MI. It provides insights into the underlying mechanisms of MI pathology and treatment.
Causal relationships between plasma lipids and sepsis: A Mendelian randomization study
Authors: Chen Jing , Chen Wei , Wu Lin , Wang Rong Hui , Xiang Jun Jun , Zheng Fu Kui , Huang Qiao Ming
Published: February 2024

Although observational studies have indicated that plasma lipids are associated with an increased risk of sepsis, due to confounders and reverse causality, the causal relationship remains unclear. This study was designed to assess the causal effects of plasma lipid levels on sepsis. We used a 2-sample Mendelian randomization (MR) method to evaluate the causal effect of plasma lipids on sepsis. MR analysis employs methods such as inverse variance weighted, MR-Egger regression, weighted median regression (WME), simple mode and weighted mode. The inverse variance weighted (IVW) method was predominantly utilized to assess causality. Heterogeneity was affirmed by Cochran Q test, while pleiotropy was corroborated by MR-Egger regression analysis. The robustness and reliability of the results were demonstrated through “leave-one-out” sensitivity analysis. Instrumental variables included 226 single-nucleotide polymorphisms (SNPs), comprising of 7 for triglyceride (TG), 169 for high-density lipoprotein cholesterol (HDL-C), and 50 for low-density lipoprotein cholesterol (LDL-C). The risk of sepsis appeared to increase with rising LDL-C levels, as indicated by the inverse variance weighted analysis (OR 1.11, 95% CI from0.99 to1.24, P = 0.068). However, no causality existed between LDL-C, HDL-C, TG and sepsis. Two-sample MR analysis indicated that increased LDL-C level is a risk factor for sepsis, while TG and HDL-C levels have protective effects against sepsis. However, no significant causal relationship was found between TG, HDL-C, and LDL-C levels and sepsis.
Procalcitonin and blood lactate level as predictive biomarkers in pediatric multiple trauma patients’ pediatric intensive care outcomes: A retrospective observational study
Authors: Colak Mustafa , Arda Kilinc Mehmet , Güven Ramazan , Onur Kutlu Nurettin
Published: February 2024

Pediatric trauma represents a significant source of morbidity and mortality in children, encompassing a broad spectrum of injuries. Despite advancements in the treatment and prevention of injuries, the risk of trauma in children remains a persistent concern. Severe trauma cases often necessitate admission to a pediatric intensive care unit (PICU). Procalcitonin, an essential biomarker that elevates bacterial infections and trauma, and elevated lactate levels can signal adverse outcomes in critically ill patients. This study retrospectively examined pediatric patients with multiple trauma treated at the Başakşehir Çam and Sakura City Hospital PICU between 2021 and 2023. The analysis sought to evaluate the relationship between initial procalcitonin and lactate levels with the duration of stay in the PICU, the length of invasive mechanical ventilation (IMV), and the duration of inotropic support. Furthermore, a comparison was made between procalcitonin and lactate levels in survivors and non-survivors, analyzing their potential influence on PICU outcomes and mortality. For pediatric multi-trauma patients, the median duration of stay in the PICU was found to be 3 days. Among these patients, 32% necessitated IMV support and utilized it for a median of 5 days. Additionally, 36% of these patients were provided inotropic drug support for a median time of 6 days. The observed mortality rate was 11%. Procalcitonin and blood lactate levels were found to have significant predictive power for mortality with odds ratios of 1.05 (P = .04) and 1.87 (P = .02), respectively. Both blood lactate and procalcitonin levels were significantly associated with the duration of IMV support, the period of inotropic drug administration, and the length of PICU stay (P < .01; P < .01; P < .01, respectively). this research underscores the prognostic value of initial procalcitonin and lactate levels about the intensive care trajectory of pediatric trauma patients. The findings suggest that both procalcitonin and lactate levels may play pivotal roles as potential biomarkers in predicting and managing clinical outcomes in this population.