bluuebunny/crossref_metadata_2025 huggingface dataset:
PCSK9 inhibition: from effectiveness to cost-effectiveness
Authors: Mercep Iveta , Strikic Dominik , Hrabac Pero , Pecin Ivan , Reiner Željko
Published: June 2024

Dyslipidaemia is a complex disorder characterised by abnormal lipid levels in the blood, including cholesterol and triglycerides, and plays an important role in the development of atherosclerotic cardiovascular disease. Most risk factors for cardiovascular disease are modifiable, and dyslipidaemia is a key factor among them. It can result from a combination of genetic and environmental factors. A distinction is made between primary dyslipidaemia, which is mainly caused by inherited genetic changes, and secondary dyslipidaemia, which is due to underlying diseases or certain medications. The treatment of dyslipidaemia has evolved over the years. In the past, statins were the first choice, but newer drugs, such as proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, have gained prominence due to their effectiveness in lowering lipids. Although recent guidelines recommend PCSK9 inhibitors for high-risk patients and patients who cannot tolerate statins, their widespread use is limited because of cost. Several meta-analyses have confirmed the efficacy and safety of PCSK9 inhibitors and have shown a significant reduction in low-density lipoprotein (LDL) cholesterol levels. However, the long-term side effects and interactions with other risk factors for cardiovascular disease remain uncertain. In addition, cost-effectiveness analyses have shown mixed results, with some countries considering PCSK9 inhibitors to be cost-effective for certain patient groups, while others consider them less economical. Meanwhile, initial data from patients using PCSK9 inhibitors support the results of the clinical trials. To summarise, PCSK9 inhibitors represent a revolutionary solution for lowering LDL cholesterol, but their cost-effectiveness remains controversial. Despite the controversy, they offer clear benefits for high-risk patients and should therefore be considered in the treatment of dyslipidaemia.
Prediction of acute coronary syndrome in patients with myeloproliferative neoplasms
Authors: Huang Jingfeng , Zhang Ping , Shen Fangjie , Zheng Xiaodong , Ding Qianjiang , Pan Yuning , Ruan Xinzhong
Published: June 2024

Background

Patients with myeloproliferative neoplasms (MPN) are exposed to a higher risk of cardiovascular disease, especially cardiovascular calcification. The present research aimed to analyze the clinical features and coronary artery calcium score (CACS) in MPN patients, and construct an effective model to predict acute coronary syndrome (ACS) in MPN patients.

Materials and methods

A total of 175 MPN patients and 175 controls were recruited from the First Affiliated Hospital of Ningbo University. Based on cardiovascular events, the MPN patients were divided into the ACS group and the non-ACS group. Multivariate Cox analysis was completed to explore ACS-related factors. Furthermore, ROC curves were plotted to assess the predictive effect of CACS combined with white blood cells (WBC) and platelet for ACS in MPN patients.

Results

The MPN group exhibited a higher CACS than the control group (133 vs. 55, P < 0.001). A total of 16 patients developed ACS in 175 MPN patients. Compared with non-ACS groups, significant differences in age, diabetes, smoking history, WBC, percentage of neutrophil, percentage of lymphocyte, neutrophil count, hemoglobin, hematocrit, platelet, lactate dehydrogenase, β2-microglobulin, and JAK2V617F mutation were observed in the ACS groups. In addition, the CACS in the ACS group was also significantly higher than that in the non-ACS group (374.5 vs. 121, P < 0.001). The multivariable Cox regression analysis identified WBC, platelet, and CACS as independent risk factors for ACS in MPN patients. Finally, ROC curves indicated that WBC, platelet, and CACS have a high predictive value for ACS in MPN patients (AUC = 0.890).

Conclusion

CACS combined with WBC and platelet might be a promising model for predicting ACS occurrence in MPN patients.
Recurrence of an undifferentiated pleomorphic pulmonary artery sarcoma 8 years after initial presentation: a case report
Authors: Bourlond Baudouin , Maurizi Niccolo , Antiochos Panagiotis , Skalidis Ioannis , Auf Der Springe Katarina , Royer Claire , Monney Pierre , Muller Olivier , Kirsch Mathias
Published: June 2024

Background

Primary cardiac tumors remain exceptionally rare, characterized by a poor prognosis. Among them, sarcomas originating in the pulmonary arteries constitute the most infrequent subgroup within primary cardiac sarcomas.

Case summary

This report presents the case of a 76-year-old female experiencing a recurrence of an undifferentiated pleomorphic intracardiac pulmonary artery sarcoma located in the right ventricular outflow tract, manifesting 8 years after initial remission. Successful outcomes were attained through a combination of surgical resection, state-of-the-art radiotherapy, and chemotherapy. This comprehensive approach proved essential for optimizing both survival and quality of life.

Discussion

The unexpectedly prolonged recurrence-free survival observed in this case underscores the effectiveness of the comprehensive multimodal treatment approach outlined in the existing literature. This highlights the pivotal role of a multidisciplinary strategy in addressing primary cardiac sarcomas, particularly those arising in the pulmonary arteries.
Seismic potential in and around the Sichuan basin from the dense GNSS network
Authors: Xu Rui , Chen Cong , He Fuxiu , Liu Xuemei
Published: June 2024

The Sichuan basin (SCB) is situated at the southeastern edge of the Tibetan Plateau where widespread seismicity has occurred. In the past decades, seismic events occurred in and around SCB have been responsible for more than 100 thousand casualties. To quantify the present-day seismic hazard of this region, especially the densely populated Chengdu-Chongqing economic zone (CCEZ), we develop a probabilistic earthquake forecast model using strain rates derived from 187 Global Navigation Satellite System (GNSS) horizontal velocities, of which 102 velocity vectors are first released. The second invariant of the strain rate tensor suggests that the Shimian County and its surroundings are exposed to the highest seismic hazard in and around SCB. The second most dangerous area is located between 103–105°E. The Chongqing area is the least dangerous. The principal strain rate axes interior of the Sichuan basin suggest that this region is experiencing broad-scale extension, which according to our knowledge, is first revealed by our dense GNSS network. The comparison between the cumulative histograms of the second invariant of geodetic strain rate and earthquake count indicates that the geodetic strain rates in this region can serve as a reliable predictor of M≥6 earthquake locations. Thus, we proceed to calculate the total seismic moment anticipated for the entire area within the next 30 years.
Investigation of the bedding effect on coal rock under Brazilian splitting tests
Authors: Hu Jie , Zhang Longfei , He Manchao
Published: June 2024

This contribution focuses on understanding the bedding effect of coal rocks under the Brazilian splitting test. First, multiple Brazilian splitting tests were performed on coal rocks with various bedding angles to systematically investigate the influence of stratification. Subsequently, numerical models with stratified structures were constructed, and a continuous–discontinuous numerical analysis method based on the cohesive zone model (CZM) was employed to conduct the corresponding numerical investigations. Results indicate that the load–displacement curves of coal rock specimens with different bedding angles can be classified into four stages: initial compaction stage, elastic deformation stage, crack rapid coalescence stage, and final destruction stage. With increase in the bedding angle, the failure patterns of coal rock specimens can be categorized into three groups: 1) stretching damage along bedding planes; 2) mixed tension and shear failure along the bedding planes and the coal matrix; and 3) stretching failure passing through the coal matrix. Furthermore, the tensile strength and cumulative acoustic emission (AE) energy–displacement relations are significantly influenced by the bedding angle. The numerical model can effectively predict the mechanical responses and fracture behavior of coal rock specimens, providing empirical parameters for the simulation of similar rock engineering.
Comparison and analysis for prediction accuracy of true triaxial rock strength criterion
Authors: He Shiwei , Cheng Hong , Cheng Lin , Yuan Feiyu , Zhang Mingming
Published: June 2024

To verify the predictive accuracy of existing strength criteria on true triaxial strength experimental data, understand the characteristics of different strength criteria, and provide a basis for selecting strength criteria for engineering applications, ten commonly used rock strength criteria were selected and divided into MC and HB types. The distribution characteristics of the yield surfaces and yield curves of different criteria were compared and analyzed in the principal stress space and the π plane. Afterwards, based on the least absolutely deviation method, these ten strength criteria were used to predict 32 sets of true triaxial rock strength experimental data. The results showed that the range of undetermined parameters for MC type strength criteria was small and easy to determine, while the range of undetermined parameter for HB type criteria was large and difficult to determine the search range, in addition, the fitting process may not converge. The fitting accuracy of strength criteria for true triaxial experimental data depends on the sensitivity of rock strength to the intermediate principal stress. PH and GP criteria are the most sensitive to changes of the intermediate principal stress, followed by MWC and ML criteria, MGC and ZZ criteria, MCJP and HBWW criteria. PH and GP criteria overestimate the effect of the intermediate principal stress, resulting in the largest prediction errors, while the other three-dimensional strength criteria have high prediction accuracy and no significant differences. The research results can provide scientific basis for engineering design, geological hazard prediction, and mineral resource development.
Metabolic syndrome and risk of subclinical hypothyroidism: a systematic review and meta-analysis
Authors: Zhong Lei , Liu Shuo , Yang Yao , Xie Tong , Liu Jifeng , Zhao Huahui , Tan Guang
Published: June 2024

Background

Subclinical hypothyroidism (SCH) is a common endocrine subclinical disorder, the main adverse consequences of which are the development of clinical hypothyroidism and the promotion of ischemic heart disease. Metabolic syndrome (MetS) is a collection of metabolic problems. The goal of this meta-analysis was to evaluate the relationship between MetS and SCH.

Methods

Suitable publications were identified using PubMed, Embase, and the Cochrane Library. The meta-analysis included only studies in English that reported odds ratio (OR) data for MetS and SCH. Two researchers combined data using a random-effects model. OR and 95% confidence intervals (CIs) were used to present the results.

Results

MetS was associated with an elevated risk of developing SCH (OR 2.56, 95% CI 1.44–4.55). However, the individual components of MetS were not associated with the risk of SCH. Subgroup analysis revealed that different definitions of MetS had varying effects on SCH. Sensitivity analysis confirmed that our results were robust.

Conclusions

This meta-analysis indicates that patients with MetS have an increased risk of SCH, while there is no significant association between the five individual components of MetS and the risk of SCH.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023454415.
A 6-year single-center prospective follow-up study of the efficacy of radiofrequency ablation for thyroid nodules
Authors: Chuanke Shi , Ming Luo , Zhideng Yan , Huan Liu
Published: June 2024

Background

Radiofrequency ablation (RFA) is an alternative modality for thyroid nodules (TNs) and many studies have also confirmed its favorable efficacy and safety. The scope of RFA increases in clinical practice and the aim of our study was to evaluate the efficacy of RFA.

Methods

We conducted a prospective study to evaluate the efficacy of RFA for thyroid nodules between January 2017 and December 2022 at our institution. We assessed the change in nodal volume, volume reduction ratio (VRR), technique effective (TE) rate, complete ablation (CA) rate, and nodal regrowth rate and time after RFA.

Results

We performed RFA for 1703 patients with TNs between January 2017 and December 2022, of which a total of 970 eligible patients were enrolled in the study. The preoperative volume of TNs was 6.23 ± 8.11ml, with 821 benign and 149 malignant nodules. The post-RFA TE and adjusted TE rate were 80% and 88.8%, respectively. CA was achieved in 145 (14.9%) patients with a mean time of 18.32± 12.98 months; nodal regrowth occurred in 15 (1.5%) patients with a mean time of 29.80 ± 12.47 months. TNs volume and VRR changed significantly at years 1 and 2 after RFA and stabilized after 5 years. A serious postoperative adverse event occurred in one patient with cervical sympathetic chain injury resulting in Horner’s syndrome. A transient or permanent damage of the recurrent laryngeal nerve could not be evaluated due to the lack of postoperative laryngoscopy, and this is a significant limitation of the study.

Conclusion

The expanded RFA indications were also effective for TNs, with no significant change in long-term efficacy.
Activity of apremilast in a patient with severe pemphigus vulgaris: case report
Authors: Delvaux Cheyenne , Bohelay Gérôme , Sitbon Ishaï-Yaacov , Soued Isaac , Alexandre Marina , Cucherousset Joël , Gilardin Laurent , Diep Antoine , Caux Frédéric , Le Roux-Villet Christelle
Published: June 2024

Introduction

Although the treatment for pemphigus vulgaris (PV) has been revolutionized by the use of rituximab combined with corticosteroids, new effective therapies with a better safety profile are needed.

Observation

A 67-year-old woman was diagnosed with severe mucosal PV, which was initially misdiagnosed as atypical Behçet’s disease. Following an unsuccessful colchicine treatment, significant improvement was observed upon the introduction of apremilast: reduced pain, fewer lesions, and a stabilized weight. The discontinuation of apremilast led to a rapid relapse. Retrospective analysis through anti-Dsg3 ELISA indicated a gradual decrease in antibody levels during the apremilast treatment.

Discussion

Apremilast, a phosphodiesterase 4 inhibitor approved for psoriasis and Behçet’s disease’s related oral ulcers treatment, demonstrated its efficacy in this PV case. This is the second case report highlighting the effectiveness of apremilast for PV treatment. Apremilast’s ability to upregulate cyclic adenosine monophosphate (cAMP) levels appears to contribute to the stabilization of keratinocyte adhesion.

Conclusion

Apremilast may be a promising therapeutic option for the treatment of pemphigus, with an innovative mechanism of action, no induced immunosuppression, and good tolerance. It could be a good alternative to steroids, in the treatment regimen of steroids combined with rituximab.
Proangiogenic properties of complement protein C1q can contribute to endometriosis
Authors: Agostinis Chiara , Toffoli Miriam , Zito Gabriella , Balduit Andrea , Pegoraro Silvia , Spazzapan Mariagiulia , Pascolo Lorella , Romano Federico , Di Lorenzo Giovanni , Mangogna Alessandro , Santin Aurora , Spedicati Beatrice , Valencic Erica , Girotto Giorgia , Ricci Giuseppe , Kishore Uday , Bulla Roberta
Published: June 2024

Endometriosis (EM) is defined as the engraftment and proliferation of functional endometrial-like tissue outside the uterine cavity, leading to a chronic inflammatory condition. While the precise etiology of EM remains elusive, recent studies have highlighted the crucial involvement of a dysregulated immune system. The complement system is one of the predominantly altered immune pathways in EM. Owing to its involvement in the process of angiogenesis, here, we have examined the possible role of the first recognition molecule of the complement classical pathway, C1q. C1q plays seminal roles in several physiological and pathological processes independent of complement activation, including tumor growth, placentation, wound healing, and angiogenesis. Gene expression analysis using the publicly available data revealed that C1q is expressed at higher levels in EM lesions compared to their healthy counterparts. Immunohistochemical analysis confirmed the presence of C1q protein, being localized around the blood vessels in the EM lesions. CD68+ macrophages are the likely producer of C1q in the EM lesions since cultured EM cells did not produce C1q in vitro. To explore the underlying reasons for increased C1q expression in EM, we focused on its established pro-angiogenic role. Employing various angiogenesis assays on primary endothelial endometriotic cells, such as migration, proliferation, and tube formation assays, we observed a robust proangiogenic effect induced by C1q on endothelial cells in the context of EM. C1q promoted angiogenesis in endothelial cells isolated from EM lesions (as well as healthy ovary that is also rich in C1q). Interestingly, endothelial cells from EM lesions seem to overexpress the receptor for the globular heads of C1q (gC1qR), a putative C1q receptor. Experiments with siRNA to silence gC1qR resulted in diminished capacity of C1q to perform its angiogenic functions, suggesting that C1q is likely to engage gC1qR in the pathophysiology of EM. gC1qR can be a potential therapeutic target in EM patients that will disrupt C1q-mediated proangiogenic activities in EM.
A combination of 5-azacytidine and nivolumab is a potentially effective rescue therapy in relapsed/refractory AITL
Authors: Ricard Laure , Cervera Pascale , Stocker Nicolas , Corre Elise , Van de Wyngaert Zoé , Banet Anne , Marjanovic Zora , Dulery Rémy , Bravetti Clotilde , Joly Anne-Christine , Baylatry Minh Tam , Coppo Paul
Published: June 2024

Introduction

Angioimmunoblastic T-cell lymphoma (AITL) is a peripheral T-cell lymphoma characterized by a T follicular helper cell phenotype expressing PD-1 (programmed cell death-1). AITL exhibits a poor response to conventional chemotherapy, with a median 5-year overall survival of 44% and a progression-free survival of 32%. Relapse is common, resulting in a median overall survival of 6 months. Recurrent mutations are detected in genes regulating DNA methylation, including TET2, DNMT3A, and IDH2 variants, along with the prevalent RHOA G17V mutation. In this context, patients treated with the hypomethylating agent 5-azacytidine achieved overall response and complete response rates of 75% and 41%, respectively. We hypothesized that targeted therapies combining anti-PD-1 checkpoint blockers with hypomethylating agents could be efficient in AITL patients and less toxic than standard chemotherapy.

Methods

Here, we report the efficacy of a regimen combining 5-azacytidine and nivolumab in nine relapsed or refractory AITL patients.

Results

This regimen was well-tolerated, especially in elderly patients. The overall response rate was 78%, including four partial responses (44%) and three complete responses (33%). Allogeneic hematopoietic stem cell transplantation was performed in two patients who reached complete response.

Discussion

These preliminary favorable results may serve as a basis for further investigation in prospective studies.
Effect of hypoxia on the post-hatching growth of the body of the fry and the caudal fin of the Atlantic Salmon (Salmo salar)
Authors: Rojas Mariana , Salvatierra Renato , Smok Carolina , Sandoval Cristian , Souza-Mello Vanessa , del Sol Mariano
Published: June 2024

Introduction

Hypoxia is a recurring problem in the fish farming industry. Currently, it is known that the exposure of fish and fry to a hypoxic environment induces important changes in their metabolism, compromising not only their development but also their reproduction and mortality rates. Our hypothesis is that hypoxia constitutes one of the etiological factors causing deformation of the body and caudal fin in this species, as well as affecting its growth.

Methods

We analyzed two hundred forty Salmo salar salmon fry, differentially cultured at 100% saturation (normoxia condition) and 60% (hypoxia condition) for 2, 4, 6, and 8 days, including a group under continuous hypoxia. We performed diaphanization and Alcian blue staining, along with standard histological techniques. The polyclonal anti-HIF-1a antibody was used as a marker of hypoxia in Salmo salar, and hypoxia in these fish was associated with the immunopositivity of this antibody.

Results and discussion

The results indicate that there is an association between exposure to hypoxia and the deformation of the body and fin, as well as an agreement between hypoxia and the total length of the fry and fin. Several months after the event occurred, we were able to find and describe angiogenesis, blood vessel disorganization, and vasodilation histologically. Finally, hypoxic cells in the fry (HIF-1a) could be recognized and confirmed as hypoxia sensors. All of this indicates that hypoxia not only affects the fry during the development phase of the event, but that its results can be evident much later and affect the fry throughout their entire ontogeny.
Effects of vaccination against COVID-19 on overactive bladder symptoms on young population
Authors: de-la-Plaza-San-Frutos Marta , García-García Elisa , Martínez-Pascual Beatriz , Esteban Isabel Mínguez , Domínguez-Balmaseda Diego , Sosa-Reina M. Dolores
Published: June 2024

Introduction

The vaccines developed against COVID-19 have different modes of action, with a primary focus on the spike protein of the virus. Adverse effects following vaccination have been reported, including local and systemic symptoms. Understanding the potential side effects on the urinary tract after vaccination is of importance. Actively investigating and comprehending the potential impact on the urinary tract, we can enhance public health strategies and pave the way for safer and more effective vaccination programs.

Methodology

The study was based on an online survey that included the Spanish Version of the Overactive Bladder Symptom Score (OABSS-S); 2,362 men and women replied to the survey. After the application of the exclusion criteria, 1,563 participants were insured. In the context of COVID-19, individuals were questioned regarding several key factors related to their vaccination status and medical history. These factors included the number of vaccine doses received, the specific type of vaccine administered, whether they had previously contracted COVID-19, and the frequency of prior infections, if applicable.

Results

A total of 1,563 (74.7% women and 27.3% men) subjects between the ages of 18 and 45 completed the survey and were included in the final analyses. The most frequently administered vaccine type was Pfizer-BioNTech (42.2%), and most subjects received three doses. The proportion of females who received the AstraZeneca vaccine and do not require to urinate during the night is significantly higher compared to males (59.1% vs. 33.3%; p<0.05). The proportion of individuals who urinate five or more times during the night is higher in those who have received a single vaccine dose than in those who have received three doses (2.2% vs. 0.1%; p<0.05).

Conclusion

COVID-19 vaccination has been found to impact the lower urinary tract (LUT) and overactive bladder (OAB). Initially, LUT symptoms worsened, and OABSS-S scores increased after the first vaccine dose in individuals under 45 years old. However, symptoms improved after receiving the third and fourth doses. Gender differences were observed in the vaccination effects. Men vaccinated with AstraZeneca reported a higher number of nighttime voids, while women vaccinated with Moderna reported more daytime voids.
Deep learning for MRI lesion segmentation in rectal cancer
Authors: Yang Mingwei , Yang Miyang , Yang Lanlan , Wang Zhaochu , Ye Peiyun , Chen Chujie , Fu Liyuan , Xu Shangwen
Published: June 2024

Rectal cancer (RC) is a globally prevalent malignant tumor, presenting significant challenges in its management and treatment. Currently, magnetic resonance imaging (MRI) offers superior soft tissue contrast and radiation-free effects for RC patients, making it the most widely used and effective detection method. In early screening, radiologists rely on patients’ medical radiology characteristics and their extensive clinical experience for diagnosis. However, diagnostic accuracy may be hindered by factors such as limited expertise, visual fatigue, and image clarity issues, resulting in misdiagnosis or missed diagnosis. Moreover, the distribution of surrounding organs in RC is extensive with some organs having similar shapes to the tumor but unclear boundaries; these complexities greatly impede doctors’ ability to diagnose RC accurately. With recent advancements in artificial intelligence, machine learning techniques like deep learning (DL) have demonstrated immense potential and broad prospects in medical image analysis. The emergence of this approach has significantly enhanced research capabilities in medical image classification, detection, and segmentation fields with particular emphasis on medical image segmentation. This review aims to discuss the developmental process of DL segmentation algorithms along with their application progress in lesion segmentation from MRI images of RC to provide theoretical guidance and support for further advancements in this field.
Development and validation of a faecal immunochemical test-based model in the work-up of patients with iron deficiency anaemia
Authors: Hernández Goretti , Quintero Enrique , Morales-Arraez Dalia , Rayado Guillermo García , Hijos-Mallada Gonzalo , Fernández-Fernández Nereida , Castro-Parga Luisa de , Álvarez-Sánchez María Victoria , Olano Carolina , Rodríguez-Alcalde Daniel , Amaral-González Carla , Alonso-Abreu Inmaculada , Nicolás-Pérez David , Carrillo-Palau Marta , González-Dávila Enrique , Gimeno-García Antonio Z.
Published: June 2024

Objective

In patients with iron deficiency anaemia (IDA), the diagnostic yield of gastroscopy and colonoscopy (bidirectional endoscopy) in detecting neoplastic lesions is low. This study aimed to develop and validate a faecal immunochemical test (FIT)-based model to optimise the work-up of patients with IDA.

Methods

Outpatients with IDA were enrolled in a prospective, multicentre study from April 2016 to October 2019. One FIT was performed before bidirectional endoscopy. Significant gastrointestinal lesions were recorded and a combined model developed with variables that were independently associated with significant colorectal lesions in the multivariate analysis. The model cut-off was selected to provide a sensitivity of at least 95% for colorectal cancer (CRC) detection, and its performance was compared to different FIT cut-offs. The data set was randomly split into two groups (developed and validation cohorts). An online calculator was developed for clinical application.

Results

The development and validation cohorts included 373 and 160 patients, respectively. The developed model included FIT value, age, and sex. In the development and validation cohorts, a model cut-off of 0.1375 provided a negative predictive value of 98.1 and 96.7% for CRC and 90.7 and 88.3% for significant colorectal lesions, respectively. This combined model reduced the rate of missed significant colorectal lesions compared to FIT alone and could have avoided more than one-fourth of colonoscopies.

Conclusion

The FIT-based combined model developed in this study may serve as a useful diagnostic tool to triage IDA patients for early endoscopic referral, resulting in considerable reduction of unnecessary colonoscopies.
Current insights into the effects of cationic biocides exposure on Enterococcus spp.
Authors: Pereira Ana P. , Antunes Patrícia , Peixe Luísa , Freitas Ana R. , Novais Carla
Published: June 2024

Cationic biocides (CBs), such as quaternary ammonium compounds and biguanides, are critical for controlling the spread of bacterial pathogens like Enterococcus spp., a leading cause of multidrug-resistant healthcare-associated infections. The widespread use of CBs in recent decades has prompted concerns about the potential emergence of Enterococcus spp. populations exhibiting resistance to both biocides and antibiotics. Such concerns arise from their frequent exposure to subinhibitory concentrations of CBs in clinical, food chain and diverse environmental settings. This comprehensive narrative review aimed to explore the complexity of the Enterococcus’ response to CBs and of their possible evolution toward resistance. To that end, CBs’ activity against diverse Enterococcus spp. collections, the prevalence and roles of genes associated with decreased susceptibility to CBs, and the potential for co- and cross-resistance between CBs and antibiotics are reviewed. Significant methodological and knowledge gaps are identified, highlighting areas that future studies should address to enhance our comprehension of the impact of exposure to CBs on Enterococcus spp. populations’ epidemiology. This knowledge is essential for developing effective One Health strategies that ensure the continued efficacy of these critical agents in safeguarding Public Health.
Prevalence of hepatitis B and C virus infections among visceral leishmaniasis patients: a systematic review and meta-analysis
Authors: Assefa Muluneh , Biset Sirak
Published: June 2024

Background

Visceral leishmaniasis (VL) patients are at high risk of acquiring hepatitis B virus (HBV) and hepatitis C virus (HCV) infections during multiple injections and the anti-leishmanial treatment possesses a potential hepatotoxic effect. This systematic review and meta-analysis determined the pooled prevalence of HBV and HCV infections in VL patients.

Methods

This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO), with the assigned number CRD42024516889, and conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search was performed using PubMed, Medline, EMBASE, Google Scholar, Web of Science, and Science Direct databases. Data were extracted using Microsoft Excel and analyzed using STATA version 11.0 software. A random-effects model was used to estimate the pooled effect size of outcome variables across studies with a 95% confidence interval and was displayed in a forest plot. The I2 statistic was used to check for heterogeneity. The presence of publication bias was determined using a funnel plot and Egger’s test with a p value <0.05 evidence of statistically significant bias.

Results

Among 216 retrieved records, seven studies were eligible for systematic review and meta-analysis. A total of 937 VL patients were examined, revealing that 105 and 93 were infected with HBV and HCV, respectively. The pooled prevalence of HBV was 16.15% (95% CI: −4.10 to 36.39), with a significant heterogeneity (I2 = 91.4%, p < 0.001). The combined prevalence of HCV was 13.74% (95% CI: 1.32–26.16, I2 = 71.6%, p = 0.003). The funnel plot (symmetry), and Egger’s test in both HBV (p value = 0.650) and HCV (p value = 0.841) revealed no publication bias. In subgroup analysis, high HBV and HCV prevalence was detected in Sudan; 20.64% (95% CI: −13.60 to 54.88) and India; 18.26% (95% CI: −0.40 to 36.92%), respectively.

Conclusion

This study revealed a high prevalence of both HBV and HCV infections in VL patients. In subgroup analysis, the prevalence of HBV and HCV was high in Sudan and India, respectively. Therefore, screening of VL patients for HBV and HCV, vaccination of VL patients in endemic regions, and collaboration between kala-azar and hepatitis elimination programs are required.

Systematic review registration

https://www.crd.york.ac.uk/prospero/export_details_pdf.php#page=1.00&gsr=0, identifier: CRD42024516889.
Retrosplenial cortex and aversive conditioning
Authors: Cheng Han Yin , Fournier Danielle I. , Todd Travis P.
Published: June 2024

The retrosplenial cortex (RSC) is well-known for its contribution to episodic memory, as well as contextual and spatial learning and memory. However, two literatures have also emerged examining the role of the RSC in aversive conditioning. The purpose of this manuscript is to review, and attempt to integrate, these two literatures. We focus on studies in which discrete cues, such as tones, predict the occurrence of aversive outcomes, such as mild shocks. Using both electrophysiological recordings and lesion methods, the first literature has examined RSC contributions to discriminative avoidance conditioning. The second, and more recent literature, has focused on the role of the RSC in Pavlovian fear conditioning. We discuss both literatures in terms of the type of information processed by the RSC, the role of the RSC in memory storage, and how the aversive conditioning literature might be consistent with a role for the RSC in contextual learning and memory.
Stem cell-like circulating tumor cells identified by Pep@MNP and their clinical significance in pancreatic cancer metastasis
Authors: Chu Xiangyu , Zhong Xiejian , Zang Shouge , Wang Mengting , Li Ping , Ma Yongsu , Tian Xiaodong , Yang Yanlian , Wang Chen , Yang Yinmo
Published: June 2024

Objective

The circulating tumor cells (CTCs) could be captured by the peptide functionalized magnetic nanoparticles (Pep@MNP) detection system in pancreatic ductal adenocarcinoma (PDAC). CTCs and the CXCR4 expression were detected to explore their clinical significance. The CXCR4+ CTCs, this is highly metastatic-prone stem cell-like subsets of CTCs (HM-CTCs), were found to be associated with the early recurrence and metastasis of PDAC.

Methods

CTCs were captured by Pep@MNP. CTCs were identified via immunofluorescence with CD45, cytokeratin antibodies, and the CXCR4 positive CTCs were assigned to be HM-CTCs.

Results

The over-expression of CXCR4 could promote the migration of pancreatic cancer cell in vitro and in vivo. In peripheral blood (PB), CTCs were detected positive in 79.0% of all patients (49/62, 9 (0–71)/2mL), among which 63.3% patients (31/49, 3 (0–23)/2mL) were HM-CTCs positive. In portal vein blood (PVB), CTCs were positive in 77.5% of patients (31/40, 10 (0–40)/2mL), and 67.7% of which (21/31, 4 (0–15)/2mL) were HM-CTCs positive CTCs enumeration could be used as diagnostic biomarker of pancreatic cancer (AUC = 0.862), and the combination of CTCs positive and CA19–9 increase shows improved diagnostic accuracy (AUC = 0.963). in addition, PVB HM-CTCs were more accurate to predict the early recurrence and liver metastasis than PB HM-CTCs (AUC 0.825 vs. 0.787 and 0.827 vs. 0.809, respectively).

Conclusions

The CTCs identified by Pep@MNP detection system could be used as diagnostic and prognostic biomarkers of PDAC patients. We identified and defined the CXCR4 over-expressed CTC subpopulation as highly metastatic-prone CTCs, which was proved to identify patients who were prone to suffering from early recurrence and metastasis.
The prognostic impact of severe grade immune checkpoint inhibitor related pneumonitis in non-small cell lung cancer patients
Authors: Sun Ni , Li Ru , Deng Haiyi , Li Qingyang , Deng Jiaxi , Zhu Yue , Mo Wenwei , Guan Wenhui , Hu Minjuan , Liu Ming , Xie Xiaohong , Lin Xinqing , Zhou Chengzhi
Published: June 2024

Objective

To compare the prognostic differences between non-small cell lung cancer (NSCLC) patients with mild and severe checkpoint inhibitor-associated pneumonitis (CIP), and explore the causes of death and prognostic risk factors in NSCLC patients with severe CIP.

Methods

A retrospective study of a cohort of 116 patients with unresectable stage III or IV NSCLC with any grade CIP from April 2016 to August 2022 were conducted. To analyze the clinical characteristics of patients with different CIP grades, patients were divided into mild CIP group (grade 1-2, n=49) and severe CIP group (grade 3-5, n=67) according to the grade of CIP. To explore the OS-related risk factors in the severe CIP group, the patients were divided into a good prognosis (GP) group (≥ median OS, n=30) and a poor prognosis (PP) group (< median OS, n=37) based on whether their overall survival (OS) were greater than median OS. Baseline clinical and laboratory data were collected for analysis.

Results

The median OS of all NSCLC patients combined with CIP was 11.4 months (95%CI, 8.070–16.100), The median OS for mild CIP and severe CIP was 22.1 months and 4.4 months respectively (HR=3.076, 95%CI, 1.904-4.970, P<0.0001). The results showed that the most common cause of death among severe CIP patients in the PP group was CIP and the most common cause in the GP group was tumor. The univariate regression analysis showed that suspension of antitumor therapy was a risk factor for poor prognosis (OR=3.598, 95%CI, 1.307-9.905, p=0.013). The multivariate logistic regression analysis showed that suspension of anti-tumor therapy (OR=4.24, 95%CI, 1.067-16.915, p=0.040) and elevated KL-6 (OR=1.002, 95%CI, 1.001-1.002, p<0.001) were independent risk factors for poor prognosis.

Conclusion

In conclusion, patients with severe CIP had a poor prognosis, especially those with elevated KL-6, and the main cause of death is immune checkpoint inhibitor-associated pneumonitis complicated with infection. In addition, anti-tumor therapy for severe CIP patients should be resumed in time and should not be delayed for too long.
Pulmonary function test-related prognostic models in non-small cell lung cancer patients receiving neoadjuvant chemoimmunotherapy
Authors: Zhang Min , Zhu Liang , Liang Sibei , Mao Zhirong , Li Xiaolin , Yang Lingge , Yang Yan , Wang Kai , Wang Pingli , Chen Weiyu
Published: June 2024

Background

This study aimed to establish a comprehensive clinical prognostic risk model based on pulmonary function tests. This model was intended to guide the evaluation and predictive management of patients with resectable stage I-III non-small cell lung cancer (NSCLC) receiving neoadjuvant chemoimmunotherapy.

Methods

Clinical pathological characteristics and prognostic survival data for 175 patients were collected. Univariate and multivariate Cox regression analyses, and least absolute shrinkage and selection operator (LASSO) regression analysis were employed to identify variables and construct corresponding models. These variables were integrated to develop a ridge regression model. The models’ discrimination and calibration were evaluated, and the optimal model was chosen following internal validation. Comparative analyses between the risk scores or groups of the optimal model and clinical factors were conducted to explore the potential clinical application value.

Results

Univariate regression analysis identified smoking, complete pathologic response (CPR), and major pathologic response (MPR) as protective factors. Conversely, T staging, D-dimer/white blood cell ratio (DWBCR), D-dimer/fibrinogen ratio (DFR), and D-dimer/minute ventilation volume actual ratio (DMVAR) emerged as risk factors. Evaluation of the models confirmed their capability to accurately predict patient prognosis, exhibiting ideal discrimination and calibration, with the ridge regression model being optimal. Survival analysis demonstrated that the disease-free survival (DFS) in the high-risk group (HRG) was significantly shorter than in the low-risk group (LRG) (P=2.57×10-13). The time-dependent receiver operating characteristic (ROC) curve indicated that the area under the curve (AUC) values at 1 year, 2 years, and 3 years were 0.74, 0.81, and 0.79, respectively. Clinical correlation analysis revealed that men with lung squamous cell carcinoma or comorbid chronic obstructive pulmonary disease (COPD) were predominantly in the LRG, suggesting a better prognosis and potentially identifying a beneficiary population for this treatment combination.

Conclusion

The prognostic model developed in this study effectively predicts the prognosis of patients with NSCLC receiving neoadjuvant chemoimmunotherapy. It offers valuable predictive insights for clinicians, aiding in developing treatment plans and monitoring disease progression.
Momelotinib – a promising advancement in the management of myelofibrosis in adults with anemia
Authors: Furqan Muhammad , Oduoye Malik O.
Published: June 2024

Myelofibrosis (MF) is a rare BCR-ABL negative myeloproliferative neoplasm characterized by clonal proliferation of stem cells, with mutations in JAK2, CALR, or MPL genes. MF presents in primary and secondary forms, with common symptoms including splenomegaly, anemia, and thrombocytopenia. Diagnostic criteria involve bone marrow examination and mutation studies. Current treatments are limited, with allogeneic stem cell transplant as the only curative option. Recent FDA approval of Momelotinib (MMB) offers new promise for MF patients with anemia. MMB, a JAK1/2 and ACVR1 inhibitor, effectively reduces spleen size, improves hemoglobin levels, and decreases transfusion dependency. The MOMENTUM trial compared MMB to danazol in JAK inhibitor-treated MF patients with anemia, showing MMB’s superior symptom relief and transfusion independence rates. Additionally, the SIMPLIFY-1 and SIMPLIFY-2 trials evaluated MMB in JAK inhibitor-naïve and experienced patients, respectively, confirming MMB’s non-inferiority to ruxolitinib in spleen volume reduction and highlighting its benefits in transfusion requirements. MMB’s unique dual inhibition mechanism addresses anemia by suppressing hepcidin production, thus enhancing erythropoiesis. These trials collectively suggest MMB as an effective treatment for MF, improving quality of life and offering a survival advantage for patients with anemia. Despite challenges, such as trial design limitations and adverse events, MMB represents a significant advancement in MF management, providing a new therapeutic option for a previously underserved patient population.
Histone modifications in head and neck squamous cell carcinoma
Authors: Mao Wei , Wang Baoxin , Huang Ruofei , Sun Zhenfeng , Yan Minzhu , Dong Pin
Published: June 2024

Head and neck cancer is the main cause of cancer death worldwide, with squamous cell carcinoma (HNSCC) being the second most frequent subtype. HNSCC poses significant health threats due to its high incidence and poor prognosis, underscoring the urgent need for advanced research. Histone modifications play a crucial role in the regulation of gene expression and influencing various biological processes. In the context of HNSCC, aberrant histone modifications are increasingly recognized as critical contributors to its development and pathologic progression. This review demonstrates the molecular mechanisms, by which histone modifications such as acetylation, methylation, phosphorylation, and ubiquitination, impact the pathogenesis of HNSCC. The dysregulation of histone-modifying enzymes, including histone acetyltransferases (HATs), histone deacetylases (HDACs), and histone methyltransferases (HMTs), is discussed for its role in altering chromatin structure and gene expression in HNSCC. Moreover, we will explore the potential of targeting histone modifications as a therapeutic strategy, highlighting current preclinical and clinical studies that investigate histone deacetylase inhibitors (HDIs) and other epigenetic drugs, referring to the completed and ongoing clinical trials on those medications.
BRCA1 foci test as a predictive biomarker of olaparib response in ovarian cancer patient-derived xenograft models
Authors: Guffanti Federica , Mengoli Ilaria , Alvisi Maria Francesca , Dellavedova Giulia , Giavazzi Raffaella , Fruscio Robert , Rulli Eliana , Damia Giovanna
Published: June 2024

Standard therapy for high-grade ovarian carcinoma includes surgery followed by platinum-based chemotherapy and poly-ADP ribose polymerase inhibitors (PARPis). Deficiency in homologous recombination repair (HRD) characterizes almost half of high-grade ovarian carcinomas and is due to genetic and epigenetic alterations in genes involved in HR repair, mainly BRCA1/BRCA2, and predicts response to PARPi. The academic and commercial tests set up to define the HRD status of the tumor rely on DNA sequencing analysis, while functional tests such as the RAD51 foci assay are currently under study, but have not been validated yet and are available for patients. In a well-characterized ovarian carcinoma patient-derived xenograft platform whose response to cisplatin and olaparib, a PARPi, is known, we assessed the association between the BRCA1 foci score, determined in formalin-fixed paraffin-embedded tumor slices with an immunofluorescence technique, and other HRD biomarkers and explored the potential of the BRCA1 foci test to predict tumors’ response to cisplatin and olaparib. The BRCA1 foci score was associated with both tumors’ HRD status and RAD51 foci score. A low BRCA1 foci score predicted response to olaparib and cisplatin, while a high score was associated with resistance to therapy. As we recently published that a low RAD51 foci score predicted olaparib sensitivity in our xenobank, we combined the two scores and showed that the predictive value was better than with the single tests. This study reports for the first time the capacity of the BRCA1 foci test to identify HRD ovarian carcinomas and possibly predict response to olaparib.
A dynamic beam switching metasurface based on angular mode-hopping effect
Authors: Hu Dongyu , He Shaowei , Li Shibin , Zhu Weiming
Published: June 2024

Fast and versatile beam forming and steering technologies are now crucial for various emerging applications, including wireless optical communications and optical switches. However, these technologies often rely on expensive components, such as spatial light modulators (SLMs) and optical phase arrays (OPAs), which come with complex and power-consuming control systems. In response to this challenge, we propose a dynamic beam-switching method inspired by the mode-hopping effect of lasers. As a proof of concept, we introduce the dynamic beam switching metasurface (DBSM) design, featuring an in-plane mechanical actuation system. Our numerical analyses, based on the finite element method (FEM), demonstrate that the proposed DBSM exhibits versatile beam forming and steering functionalities. These include beam splitting and omnidirectional beam steering. Moreover, we anticipate that the tuning speed of the DBSM will reach the kilohertz (kHz) range or even higher when utilizing a microelectromechanical systems (MEMS) actuator, building upon pioneering research in this field. We envision it holds promising applications in areas such as light detection and ranging (LiDAR), optical wireless communication devices, and optical switches.