bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of circulating IGF-1 and IGFBP-2 on cardiovascular prognosis in patients with acute coronary syndrome
Authors: Wang Wei , Yu Kang , Zhao Shou-Yong , Mo De-Gang , Liu Jia-Hui , Han Li-Jinn , Li Tai , Yao Heng-Chen
Published: March 2023

Background

While insulin-like growth factor 1 (IGF-1) exerts a cardioprotective effect in the setting of atherosclerosis, insulin-like growth factor binding protein 2 (IGFBP-2) is involved in metabolic syndrome. Although IGF-1 and IGFBP-2 are known to be predictors for mortality in patients with heart failure, their use in clinic as prognostic biomarkers for acute coronary syndrome (ACS) requires investigation. We evaluated the relationship between IGF-1 and IGFBP-2 levels at admission and the risk of major adverse cardiovascular events (MACEs) in patients with ACS.

Methods

A total of 277 ACS patients and 42 healthy controls were included in this prospective cohort study. Plasma samples were obtained and analyzed at admission. Patients were followed for MACEs after hospitalization.

Results

Among patients who suffered acute myocardial infarction, plasma levels of IGF-1 and IGFBP-2 were lower and higher, respectively, as compared to healthy controls (both p < 0.05). The mean follow-up period was 5.22 (1.0–6.0) months and MACEs incidence was 22.4% (62 of 277 patients). Kaplan–Meier survival analysis revealed that patients with low IGFBP-2 levels had a greater event-free survival rate than patients with high IGFBP-2 levels (p < 0.001). Multivariate Cox proportional hazards analysis revealed IGFBP-2, but not IGF-1, to be a positive predictor of MACEs (hazard ratio 2.412, 95% CI 1.360–4.277; p = 0.003).

Conclusion

Our findings suggest that high IGFBP-2 levels are associated with the development of MACEs following ACS. Moreover, IGFBP-2 is likely an independent predictive marker of clinical outcomes in ACS.
Minimally invasive epicardial left-ventricular lead implantation and simultaneous left atrial appendage closure
Authors: Petersen Johannes , Alassar Yousuf , Yildirim Yalin , Tönnis Tobias , Reichenspurner Hermann , Pecha Simon
Published: March 2023

Background

Atrial fibrillation (AF) is common in patients with heart failure resulting in a high prevalence of AF in patients receiving Cardiac Resynchronization Therapy (CRT) implantation. In patients, unsuitable for transvenous left ventricular (LV)-lead implantation, epicardial LV-lead implantation represents a valuable alternative. Epicardial LV-lead placement can be achieved totally thoracoscopical or via minimally invasive left lateral thoracotomy. In patients with atrial fibrillation, concomitant left atrial appendage (LAA) clipping is feasible via the same access. Therefore, the aim of our study was the analysis of safety and efficacy of epicardial LV lead implantation and concomitant LAA clipping via minimally invasive left-lateral thoracotomy.

Methods

Between December 2019 and March 2022, 8 patients received minimally invasive left atrial LV-lead implantation with concomitant LAA closure using the AtriClip. Transesophageal echocardiography (TEE) was performed to intraoperatively guide and control LAA closure.

Results

Mean patients age was 64 ± 11.2 years, 67% were male patients. Minimally invasive left-lateral thoracotomy was used in 6 patients while a totally thoracoscopic approach was performed in 2 cases. Epicardial lead implantation was successfully performed in all patients with good pacing threshold (mean 0.8 ± 0.2 V) and sensing values (10.1 ± 2.3 mV). Posterolateral position of the LV lead was achieved in all patients. Furthermore, successful LAA closure was confirmed during TEE in all patients. No procedure-related complications occurred in any of the patients. Two patients additionally received simultaneous laser lead extraction during the same procedure. Complete lead extraction was achieved in both patients. All patients were extubated in the OR and had an uneventful postoperative course.

Conclusion

Our study highlights a novel treatment approach for patients with atrial fibrillation and the necessity of epicardial LV leads. Placement of a posterolateral LV lead position with concomitant occlusion of the left atrial appendage via a minimally-invasive left-lateral thoracotomy or even a totally thoracoscopic approach is safe and feasible with superior cosmetic result and complete occlusion of the left atrial appendage.
Two-staged uplift of the southeast margin of the Tibetan plateau revealed by river longitudinal profiles
Authors: Pan Rouxian , Han Zhiyong , Su Qi , Li Guangwei , Li Xusheng , Li Yalin , Wang Xianyan
Published: March 2023

The Jinsha River, upstream of the Yangtze River, flows through the southeastern margin of the plateau, providing an opportunity to study the plateau uplift relative to the Sichuan basin through fluvial geomorphology. Eight tributaries of the Jinsha River located at the transition boundary from the plateau to the basin were analyzed for the feature of longitudinal profile and its evolution. The spatial distribution of slope-break knickpoints in the catchment was determined by slope-area analysis and integration analysis. Further, the magnitude and timing of the base level lowering (i.e., uplift of the Tibetan Plateau) were estimated by reconstructing the river longitudinal profile. The results show that there are two levels of slope-break knickpoints, with average elevations of 2865 m and 1523 m, corresponding to base levels relatively lowering of 1400 m and 1100 m, respectively. With reference to the long-term downcutting rate of the Jinsha River, the timings of these two phases base level lowering and uplifts are estimated to be ∼21–24 and ∼7–13 Ma, respectively. These are close to the timing of two uplifts revealed by inversion modeling of river longitudinal profiles. Therefore, the uplift of the studied region on the Tibetan Plateau can be divided into two stages, the early stage (∼20 Ma) uplift from 1500 to 2900 m and the late stage (∼10 Ma) uplift from 2900 to 4000 m, which further supports the staged outside uplift of the Tibetan Plateau.
Spatio-temporal change monitoring for surface water on the Qinghai-Tibet Plateau from 1990 to 2020 using remote sensing
Authors: Sui Tianbo , Ye Chengming , Tang Rong , Wei Ruilong
Published: March 2023

Detecting and analyzing changes of water resources is critical for human survival and societal development in the Qinghai Tibet Plateau (QTP). We implemented the cosine similarity method to complete the migration of samples and achieve a more accurate random forest classifier (mean Kappa = 0.872) for each period. Based on these classifiers and 45,370 Landsat images, we estimated the surface water distribution of the QTP for six periods between 1990 and 2020 based on the Google Earth Engine platform. The results indicate that the QTP has a surface water area of 57,229 ± 3,248 km2 (1990–1995), 58,444 ± 3,248 km2 (1996–2000), 67,319 ± 3,704 km2 (2001–2005), 67,399 ± 2,798 km2 (2006–2010), 70,286 ± 3,033 km2 (2011–2015), 75,176 ± 2,785 km2 (2016–2020), that the area of water rose by ap-proximately 31.3% and continued to increase. The area of permanent water remained constant between 1990 and 2020 at 47,280 km2. On the QTP, the change in water area can be split into four regions: rapid increase (Qiangtang Plateau), slow increase (eastern basins), decrease (northern and northeastern basins), and relatively stable (southern basins). About 186,408 km2 area of land is significantly losing water bodies, while about 589,567 km2 area of land is significantly gaining water bodies. This study provides higher accuracy temporal distribution data of water bodies in the Qinghai-Tibet Plateau, and quantitatively evaluates the area changes of water bodies from multiple spatial scales. Research provides an important scientific reference for hydrological research and effective management of water resources in important rivers in the QTP.
Clinical and molecular features of four Brazilian families with multiple endocrine neoplasia type 1
Authors: Miranda Isabella Santiago de Melo , Valadares Luciana Pinto , Barra Gustavo Barcelos , Mesquita Pedro Góes , de Santana Lidiana Bandeira , de Castro Lucas Faria , Rita Ticiane Henriques Santa , Naves Luciana Ansaneli
Published: March 2023

Objective

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome characterized by its clinical variability and complexity in diagnosis and treatment. We performed both clinical and molecular descriptions of four families with MEN1 in a follow-up at a tertiary center in Brasília.

Methods

From a preliminary review of approximately 500 medical records of patients with pituitary neuroendocrine tumor (PitNET) from the database of the Neuroendocrinology Outpatient Clinic of the University Hospital of Brasília, a total of 135 patients met the criteria of at least two affected family members. From this cohort, we have identified 34 families: only four with a phenotype of MEN1 and the other 30 families with the phenotype of familial isolated pituitary adenoma (FIPA). Eleven patients with a clinical diagnosis of MEN1 from these four families were selected.

Results

Variants in MEN1 gene were identified in all families. One individual from each family underwent genetic testing using targeted high-throughput sequencing (HTS). All patients had primary hyperparathyroidism (PHPT), and the second most common manifestation was PitNET. One individual had well-differentiated liposarcoma, which has been previously reported in a single case of MEN1. Three variants previously described in the database and a novel variant in exon 2 have been found.

Conclusions

The study allowed the genotypic and phenotypic characterization of families with MEN1 in a follow-up at a tertiary center in Brasília.
Oxidative stress on vessels at the maternal-fetal interface for female reproductive system disorders: Update
Authors: Zhang Chenlu , Guo Yaxin , Yang Yan , Du Zhaojin , Fan Yunhui , Zhao Yin , Yuan Suzhen
Published: March 2023

Considerable evidence shows that oxidative stress exists in the pathophysiological process of female reproductive system diseases. At present, there have been many studies on oxidative stress of placenta during pregnancy, especially for preeclampsia. However, studies that directly focus on the effects of oxidative stress on blood vessels at the maternal-fetal interface and their associated possible outcomes are still incomplete and ambiguous. To provide an option for early clinical prediction and therapeutic application of oxidative stress in female reproductive system diseases, this paper briefly describes the composition of the maternal-fetal interface and the molecular mediators produced by oxidative stress, focuses on the sources of oxidative stress and the signaling pathways of oxidative stress at the maternal-fetal interface, expounds the adverse consequences of oxidative stress on blood vessels, and deeply discusses the relationship between oxidative stress and some pregnancy complications and other female reproductive system diseases.
A survey on parameters estimation of the proton exchange membrane fuel cells based on the swarm-inspired optimization algorithms
Authors: Razmjooy Navid
Published: March 2023

The main purpose of this study is to review various swarm-inspired optimization algorithms to discuss the significance of some established works in this area. Accurate parameter estimation is required to guarantee proper modeling of PEMFCs. However, because PEMFC models are complex, non-linear, and multivariate, parameter estimation is quite difficult. To estimate the linear and non-linear parameters of a PEMFC model in real time, this work investigates PEMFC model parameters estimation methods with a focus on online identification algorithms, which are thought of as the foundation of designing a global energy management strategy. Various PEMFC models with various classifications and objectives are initially addressed in this regard. The parameters of two well-known semi-empirical models in the literature, including 500 W BCS PEMFC and the 6 kW NedSstack PS6 PEMFC have then been identified using some potential swarm-inspired optimization algorithms for practical applications, such that the TSD error for the NedStack PS6 and BCS PEMFC based on the swarm-inspired optimization algorithms provide averagely 2.22 and 0.047, respectively. Finally, the obtained accomplishments and upcoming difficulties are highlighted.
Determinants of waste separation behavior Tabriz, Iran: An application of the theory of planned behavior at health center
Authors: Babazadeh Towhid , Ranjbaran Soheila , Kouzekanani Kamiar , Abedi Nerbin Sanaz , Heizomi Haleh , Ramazani Mohammad Ebrahim
Published: March 2023

Background: Identifying factors that may influence waste separation behavior can lead to more effective waste separation, better recycling plans in a community, and more effective and efficient waste management interventions. The purpose of the survey was to identify the key factors behind such behavior.

Methods: The scientific inquiry was cross-sectional in nature, took place in Tabriz, Iran, and employed multistage random sampling to recruit the study’s 360 participants. The data collection process took place between September 2018 and February 2019. A Theory of Planned Behavior-driven questionnaire was developed by the research team for the purpose of data collection. The structural equation modeling (SEM) approach was deployed for data analysis.

Results: The structural equation modeling of the data showed the most important determinants of behavioral intention were perceived behavioral control (β = 0.39, p < 0.05), moral commitments (β = 0.19, p < 0.05), and perceived policy effectiveness (β = 0.12, p < 0.05). The strongest determinants of waste separation behavior were behavioral intention (β = 0.29, p < 0.05) and perceived behavioral control (β = 0.25, p < 0.05). In addition, age-group and gender differences were statistically related to waste separation behavior significantly (p < 0.05).

Conclusion: Recycling investors and other stakeholders should focus on perceived behavioral control and intention in designing and implementing waste separation programs.
Outcomes of programmed death protein-1 inhibitors treatment of chronic active Epstein Barr virus infection: A single center retrospective analysis
Authors: Ma Yaxian , Zhang Peiling , Bao Yuhan , Luo Hui , Wang Jiachen , Huang Liang , Zheng Miao
Published: March 2023

Introduction

Chronic active Epstein-Barr virus (CAEBV) disease is a high-mortality disease, which is characterized by persistent infectious mononucleosis-like symptoms. There is no standard treatment for CAEBV and allogeneic hematopoietic stem cell transplantation (HSCT) was considered the only potentially therapeutic approach. PD-1 inhibitors have achieved high response in many Epstein-Barr virus-related diseases. In this single-center retrospective analysis, we report the outcomes of PD-1 inhibitors treatment of CAEBV.

Methods

All CAEBV patients without hemophagocytic lymphohistiocytosis (HLH), who were treated with PD-1 inhibitors in our center between 6/1/2017 and 12/31/2021, were retrospectively analyzed. The efficacy and safety of the PD-1 inhibitors were evaluated.

Results

Among the sixteen patients with a median age at onset of 33 years (range, 11-67 years), twelve patients responded to PD-1 inhibitors and the median progression-free survival (PFS) was 11.1 months (range, 4.9-54.8 months). Three achieved clinical complete response (clinical CR), as well as molecular CR. Five patients achieved and remained partial response (PR), and four converted from PR to no response (NR). For three CR patients, the median time and cycles from the first application of PD-1 inhibitor to clinical CR were 6 weeks (range, 4-10 weeks) and 3 cycles (range, 2-4 cycles), and molecular CR was achieved after a median of 16.7 weeks (range, 6.1-18.4 weeks) and 5 cycles (range, 3-6 cycles) of PD-1 inhibitor infusion. No immune-related adverse events have been observed except for one patient who suffered immune-related pancreatitis. There was no correlation of treatment outcome with blood count, liver function, LDH, cytokine or ferritin levels. NK cell function, PD-L1 expression in tumor tissue and gene mutation possibly correlated with treatment response.

Discussion

In patients with CAEBV, PD-1 inhibitors have tolerable toxicity and comparable outcomes while improving quality of life and financial toxicity. Larger prospective studies and longer follow-up time is needed to be conducted.
Mucosal-associated invariant T cells in patients with axial spondyloarthritis
Authors: van der Meer Rienk Gerben , Spoorenberg Anneke , Brouwer Elisabeth , Doornbos-van der Meer Berber , Boots Annemieke M. H. , Arends Suzanne , Abdulahad Wayel H.
Published: March 2023

Background

Several studies implicate Th17-cells and its cytokine (IL-17) in disease pathogenesis of spondyloarthritis (SpA), with available evidence supporting a pathogenic role of CD8+ T-cells. However, data on the involvement of CD8+ mucosal-associated invariant T-cells (MAIT) and their phenotypic characterization and inflammatory function including IL-17 and Granzyme A production in a homogenous population of SpA-patients with primarily axial disease (axSpA) are lacking.

Objectives

Quantify and characterize the phenotype and function of circulating CD8+MAIT-cells in axSpA-patients with primarily axial disease.

Methods

Blood samples were obtained from 41 axSpA-patients and 30 age- and sex-matched healthy controls (HC). Numbers and percentages of MAIT-cells (defined as CD3+CD8+CD161highTCRVα7.2+) were determined, and production of IL-17 and Granzyme A (GrzA) by MAIT-cells were examined by flow cytometry upon in vitro stimulation. Serum IgG specific for CMV was measured by ELISA.

Results

No significant differences in numbers and percentages of circulating MAIT-cells were found between axSpA-patients and HCr zijn meer resultaten de centrale memory CD8 T cellen. cellen van patirculating MAIT cells.. Further phenotypic analysis revealed a significant decrease in numbers of central memory MAIT-cells of axSpA-patients compared to HC. The decrease in central memory MAIT-cells in axSpA patients was not attributed to an alteration in CD8 T-cell numbers, but correlated inversely with serum CMV-IgG titers. Production of IL-17 by MAIT-cells was comparable between axSpA-patients and HC, whereas a significant decrease in the production of GrzA by MAIT-cells from axSpA-patients was observed.

Conclusions

The decrease in cytotoxic capability of circulating MAIT-cells in axSpA-patients might implicate that these cell types migrate to the inflamed tissue and therefore associate with the axial disease pathogenesis.
High-resolution characterization of the development and decay of seasonal hypoxia in the Gulf of Riga, Baltic Sea
Authors: Liblik Taavi , Stoicescu Stella-Theresa , Buschmann Fred , Lilover Madis-Jaak , Lips Urmas
Published: March 2023

The Gulf of Riga is a shallow basin in the eastern Baltic Sea connected to the Central Baltic Sea via shallow straits. Seasonal oxygen depletion occurs in the deep layer of the gulf. We conducted hourly measurements of dissolved oxygen, temperature, and salinity in the deep layer (50 m) of the gulf and observed the full cycle of development and relaxation of hypoxia in 2021. Hypoxia (<2.9 mg l-1) first occurred on 27 June and was observed for 71 days until its complete decay on 22 October. Average oxygen decline of 0.10 mg l-1 d-1 from saturation in mid-April until mid-July and 0.04 mg l-1 d-1 onwards until the end of August were observed. This seasonal pattern was superimposed by short-term variability in time scales from hours to days and was probably caused by inertial oscillations, (sub)mesoscale processes, deep layer currents, and pycnocline movements. Ventilation events with a relatively low impact and duration of up to ten days occurred in the deep layer due to the inflows of the saltier water from the Central Baltic. The inflowed water originated from the upper layer in winter and the thermocline in summer and was almost saturated in oxygen. Mostly mixing with existing oxygen-depleted water in the Gulf of Riga, but also local consumption declined the oxygen levels in the inflow water before it arrived at the observing station. Monthly standard deviations in oxygen varied from 0.3 to 2.8 mg l-1 and illustrated the added value of Eulerian measurements to complement the conventional monitoring.
The cut-off value for HOMA-IR discriminating the insulin resistance based on the SHBG level in women with polycystic ovary syndrome
Authors: Biernacka-Bartnik Aleksandra , Kocełak Piotr , Owczarek Aleksander Jerzy , Choręza Piotr Stanisław , Markuszewski Leszek , Madej Paweł , Puzianowska-Kuźnicka Monika , Chudek Jerzy , Olszanecka-Glinianowicz Magdalena
Published: March 2023

Introduction

The study aimed to estimate the cut-off value for homeostatic model assessment for insulin resistance (HOMA-IR) discriminating the insulin resistance based on the sex hormones binding globulin (SHBG) level in women with polycystic ovary syndrome (PCOS).

Materials and methods

Data from medical records of 854 Caucasian women diagnosed with PCOS were analyzed. Anthropometric data, fasting plasma glucose, insulin and SHBG levels were measured. HOMA-IR was calculated with a standard formula. The cut-off value was calculated using receiver-operating characteristics.

Results

Circulating SHBG levels below the normal range (26.1 nmol/L) were found in 25.4% of study participants. This subgroup had a significantly higher BMI, fasting glucose and insulin concentrations and HOMA-IR values. Empirical optimal cut-off values for HOMA-IR corresponding to low SHBG levels was ≥2.1 [area under the curve (AUC) 0.73, accuracy 0.65, sensitivity 72.3%, specificity 63.1%, positive predictive value (PPV) 40.0%, negative predictive value (NPV) 87.0%].

Conclusions

Our study suggests that the cut-off point for HOMA-IR discriminating the insulin resistance based on the SHBG level, in young Caucasian women with polycystic ovary syndrome is 2.1, and is consistent with the cut-off value adopted by the European Group for the Study of Insulin Resistance (above 2.0).
Extent of the protection afforded by histo-blood group polymorphism against rotavirus gastroenteritis in metropolitan France and French Guiana
Authors: Masson Lydie , Barbé Laure , Henaff Fanny , Ahmed Tasnuva , Le Moullac-Vaidye Béatrice , Peltier Cécile , Marchand Sarah S , Scherdel Pauline , Vibet Marie-Anne , Ruvoën-Clouet Nathalie , Elenga Narcisse , Imbert-Marcille Berthe-Marie , Gras-Le Guen Christèle , Le Pendu Jacques
Published: March 2023

Human rotaviruses attach to histo-blood group antigens glycans and null alleles of the ABO, FUT2 and FUT3 genes seem to confer diminished risk of gastroenteritis. Yet, the true extent of this protection remains poorly quantified. Here, we conducted a prospective study to evaluate the risk of consulting at the hospital in non-vaccinated pediatric patients according to the ABO, FUT2 (secretor) and FUT3 (Lewis) polymorphisms, in Metropolitan France and French Guiana. At both locations, P genotypes were largely dominated by P [8]-3, with P [6] cases exclusively found in French Guiana. The FUT2 null (nonsecretor) and FUT3 null (Lewis negative) phenotypes conferred near full protection against severe gastroenteritis due to P [8]-3 strains (OR 0.03, 95% CI [0.00–0.21] and 0.1, 95% CI [0.01–0.43], respectively in Metropolitan France; OR 0.08, 95% CI [0.01–0.52] and 0.14, 95%CI [0.01–0.99], respectively in French Guiana). Blood group O also appeared protective in Metropolitan France (OR 0.38, 95% CI [0.23–0.62]), but not in French Guiana. The discrepancy between the two locations was explained by a recruitment at the hospital of less severe cases in French Guiana than in Metropolitan France. Considering the frequencies of the null ABO, Secretor and Lewis phenotypes, the data indicate that in a Western European population, 34% (95% CI [29%; 39%]) of infants are genetically protected against rotavirus gastroenteritis of sufficient severity to lead to hospital visit.
Autosomal dominant and autosomal recessive polycystic kidney disease: hypertension and secondary cardiovascular effect in children
Authors: Lucchetti L. , Chinali M. , Emma F. , Massella L.
Published: March 2023

Autosomal dominant (ADPKD) and autosomal recessive (ARPKD) polycystic kidney disease are the most widely known cystic kidney diseases. They are significantly different from each other in terms of genetics and clinical manifestations. Hypertension is one of the main symptoms in both diseases, but the age of onset and secondary cardiovascular complications are significantly different. Most ARPKD children are hypertensive in the first year of life and need high doses of hypertensive drugs. ADPKD patients with a very early onset of the disease (VEOADPKD) develop hypertension similarly to patients with ARPKD. Conversely, a significantly lower percentage of patients with classic forms of ADPKD develops hypertension during childhood, although probably more than originally thought. Data published in the past decades show that about 20%–30% of ADPKD children are hypertensive. Development of hypertension before 35 years of age is a known risk factor for more severe disease in adulthood. The consequences of hypertension on cardiac geometry and function are not well documented in ARPKD due to the rarity of the disease, the difficulties in collecting homogeneous data, and differences in the type of parameters evaluated in different studies. Overall, left ventricular hypertrophy (LVH) has been reported in 20%–30% of patients and does not always correlate with hypertension. Conversely, cardiac geometry and cardiac function are preserved in the vast majority of hypertensive ADPKD children, even in patients with faster decline of kidney function. This is probably related to delayed onset of hypertension in ADPKD, compared to ARPKD. Systematic screening of hypertension and monitoring secondary cardiovascular damage during childhood allows initiating and adapting antihypertensive treatment early in the course of the disease, and may limit disease burden later in adulthood.
Effects of the administration of Shinbaro 2 in a rat lumbar disk herniation model
Authors: Kim Won Kyung , Shin Joon-Shik , Lee Jinho , Koh Wonil , Ha In-Hyuk , Park Hyen Joo , Lee Sang Kook , Hong Jin Young
Published: March 2023

The current standard for the pharmacological management of lumbar disk herniation (LDH), involving non-steroidal anti-inflammatory drugs, muscle relaxants, and opioid analgesics, often carries a risk of adverse events. The search for alternative therapeutic options remains a vital objective, given the high prevalence of LDH and the critical impact on the quality of life. Shinbaro 2 is a clinically effective herbal acupuncture against inflammation and various musculoskeletal disorders. Therefore, we explored whether Shinbaro 2 exerts protective effects in an LDH rat model. The results showed that Shinbaro 2 suppressed pro-inflammatory cytokines, interleukin-1 beta, tumor necrosis factor-alpha, disk degeneration-related factors, matrix metalloproteinase-1,−3,−9, and ADAMTS-5 in LDH rats. Shinbaro 2 administration reinstated a behavioral activity to a normal level in the windmill test. The results indicated that Shinbaro 2 administration restored spinal cord morphology and functions in the LDH model. Therefore, Shinbaro 2 exerted a protective effect in LDH via actions on inflammatory responses and disk degeneration, indicating that future research is warranted to assess the action mechanisms further and validate its effects.
Chronic salmon calcitonin exerts an antidepressant effect via modulating the p38 MAPK signaling pathway
Authors: Zhu Wenhui , Li Weifen , Jiang Jian , Wang Dilong , Mao Xinliang , Zhang Jin , Zhang Xunzhi , Chang Jinlong , Yao Peijia , Yang Xiuyan , Da Costa Clive , Zhang Ying , Yu Jiezhong , Li Huiliang , Li Shupeng , Chi Xinjin , Li Ningning
Published: March 2023

Depression is a common recurrent psychiatric disorder with a high lifetime prevalence and suicide rate. At present, although several traditional clinical drugs such as fluoxetine and ketamine, are widely used, medications with a high efficiency and reduced side effects are of urgent need. Our group has recently reported that a single administration of salmon calcitonin (sCT) could ameliorate a depressive-like phenotype via the amylin signaling pathway in a mouse model established by chronic restraint stress (CRS). However, the molecular mechanism underlying the antidepressant effect needs to be addressed. In this study, we investigated the antidepressant potential of sCT applied chronically and its underlying mechanism. In addition, using transcriptomics, we found the MAPK signaling pathway was upregulated in the hippocampus of CRS-treated mice. Further phosphorylation levels of ERK/p38/JNK kinases were also enhanced, and sCT treatment was able only to downregulate the phosphorylation level of p38/JNK, with phosphorylated ERK level unaffected. Finally, we found that the antidepressant effect of sCT was blocked by p38 agonists rather than JNK agonists. These results provide a mechanistic explanation of the antidepressant effect of sCT, suggesting its potential for treating the depressive disorder in the clinic.
Comparative analysis of lipid components in fresh Crassostrea Hongkongensis (raw) and its dried products by using high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC/Q-TOF-MS)
Authors: Sun Qunzhao , Wang Yunru , Cai Qiuxing , Pang Tingcai , Lan Weibing , Li Laihao
Published: March 2023

The lipids of the oyster (Crassostrea hongkongensis) have a special physiological activity function, which is essential to maintain human health. However, comprehensive research on their lipids species and metabolism is not so common. In our study, based on the high-performance liquid chromatography/quadrupole time-of-flight mass spectrometer (HPLC/Q-TOF-MS), the non-targeted lipidomics research of Crassostrea hongkongensis fresh and dried products was determined. Meanwhile, we analyzed its lipid outline, screened the differences between the lipid molecules of Crassostrea hongkongensis fresh and dried products, and determined the lipid metabolic pathway. Results showed that 1,523 lipid molecules were detected, in which polyunsaturated fatty acids mostly existed in such lipids as phosphoglyceride. Through the multivariate statistical analysis, according to the conditions of P < 0.05, FC > 2 or FC < 0.05, and VIP > 1.2, 239 different lipid molecules were selected, including 37 fatty acids (FA), 60 glycerol phospholipids (GP), 20 glycerin (GL), 38 sheath lipids (SP), 31 steroid lipids (ST), 36 polyethylene (PK), and 17 progesterone lipids (PR). Combined with the Kyoto Encyclopedia of Genes and Genomes (KEGG), the differential lipid molecules were analyzed to mainly determine the role of the glycerin phospholipid metabolic pathway. As a whole, the results of this study provide the theoretical basis for the high-value utilization of oysters and are helpful to the development of oysters' physiological activity functions and deep utilization.
QTc prolongation risk among patients receiving oral targeted antineoplastic medications: A real-world community-based oncology analysis
Authors: Reeves David J. , Russell Molly , Rao Vijay U.
Published: March 2023

Introduction

Thirty oral targeted antineoplastic agents are associated with prolongation of the QT interval. However, limited data exists regarding QTc prolongation and associated risk factors in the ambulatory oncology setting.

Methods

This retrospective study was completed to describe QTc prolongation incidence among patients receiving oral targeted tyrosine kinase inhibitors (TKI) and identify potential risk factors in the ambulatory community-based oncology clinic.

Results

Of the 341 patients identified as receiving oral TKI, 49 with a baseline and follow-up ECG were included. The incidence of QTc prolongation (QTc > 470 ms in males, QTc > 480 ms in females, or >20 ms increase in QTc from baseline) was 24%. Three patients developed significant QTc prolongation (QTc >500 ms or >60 ms increase in QTc from baseline). No patients discontinued therapy primarily due to QTc prolongation or experienced symptomatic torsades de pointes. Analysis of risk factors demonstrated that patients with QTc prolongation were more likely to receive concomitant therapy with a loop diuretic (41% vs 11%, respectively, p=0.029).

Discussion

The frequency of QTc prolongation may be higher in the real-world setting than that observed in clinical trials; however, continuation of therapy may be possible. Patients receiving concomitant loop diuretics should be monitored more closely for QTc prolongation and electrolyte abnormalities.
Construction of an individualized brain metabolic network in patients with advanced non-small cell lung cancer by the Kullback-Leibler divergence-based similarity method: A study based on 18F-fluorodeoxyglucose positron emission tomography
Authors: Yu Jie , Hua Lin , Cao Xiaoling , Chen Qingling , Zeng Xinglin , Yuan Zhen , Wang Ying
Published: March 2023

Background

Lung cancer has one of the highest mortality rates of all cancers, and non-small cell lung cancer (NSCLC) accounts for the vast majority (about 85%) of lung cancers. Psychological and cognitive abnormalities are common in cancer patients, and cancer information can affect brain function and structure through various pathways. To observe abnormal brain function in NSCLC patients, the main purpose of this study was to construct an individualized metabolic brain network of patients with advanced NSCLC using the Kullback-Leibler divergence-based similarity (KLS) method.

Methods

This study included 78 patients with pathologically proven advanced NSCLC and 60 healthy individuals, brain 18F-FDG PET images of these individuals were collected and all patients with advanced NSCLC were followed up (>1 year) to confirm their overall survival. FDG-PET images were subjected to individual KLS metabolic network construction and Graph theoretical analysis. According to the analysis results, a predictive model was constructed by machine learning to predict the overall survival of NSLCL patients, and the correlation with the real survival was calculated.

Results

Significant differences in the degree and betweenness distributions of brain network nodes between the NSCLC and control groups (p<0.05) were found. Compared to the normal group, patients with advanced NSCLC showed abnormal brain network connections and nodes in the temporal lobe, frontal lobe, and limbic system. The prediction model constructed using the abnormal brain network as a feature predicted the overall survival time and the actual survival time fitting with statistical significance (r=0.42, p=0.012).

Conclusions

An individualized brain metabolic network of patients with NSCLC was constructed using the KLS method, thereby providing more clinical information to guide further clinical treatment.
Neoadjuvant osimertinib and chemotherapy for stage IIIA primary pulmonary carcinosarcoma with EGFR 19DEL mutation: A case report
Authors: Wang Hongming , Wu Zhijun , Du Yangfeng , Wu Tao , Tian Wei , Dong Wen , Cai Juan , Zheng Jiang , Zhang Yan , Li Shiyan , Xu Wei , Qin Jing , Xiao Zemin
Published: March 2023

Epidermal growth factor receptor (EGFR) mutations have been frequently detected in patients with pulmonary adenocarcinoma. EGFR Exon 19Del and 21L858R mutations are the two most common EGFR mutations. EGFR-tyrosine kinase inhibitors (TKIs) are widely employed to treat patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations. Recently, there has been rapid growth in clinical trials assessing neoadjuvant targeted therapy, indicating good application prospects owing to high efficiency and low toxicity. Herein, we discuss the case of a 56-year-old male patient who was initially diagnosed with stage IIIA pulmonary adenocarcinoma (AJCC,8th edition) of the left lower lung with an EGFR Exon 19Del mutation. The patient was treated with osimertinib but failed to undergo timely review and surgery. Subsequently, the patient underwent two cycles of neoadjuvant chemotherapy (NAC) combined with neoadjuvant targeted therapy. After the tumor load and size had significantly decreased, radical surgery was successfully performed under thoracoscopy. However, postoperative pathology revealed carcinosarcoma, pT2aN0M0, stage IB, and the pathological response was 50%. The present case report provides practical clinical evidence for the application of neoadjuvant targeted therapy combined with chemotherapy for locally advanced primary pulmonary carcinosarcoma with EGFR mutation.
Incidence, risk factors and ophthalmic clinical characteristic of ethambutol-induced optic neuropathy: 7-year experience
Authors: Chaitanuwong Pareena , Srithawatpong Supaporn , Ruamviboonsuk Paisan , Apinyawasisuk Supanut , Watcharapanjamart Akechanok , Moss Heather E.
Published: March 2023

Background

The purpose of this research was to investigate the characteristics, clinical manifestations, incidence, and risk factors in ethambutol-induced optic neuropathy (EON) in the Thai population.

Methods

Patients treated with ethambutol for tuberculosis (TB) were retrospectively identified in the medical record of a tertiary hospital in Thailand from January 2012 to August 2019. Development of EON was determined through review of ophthalmology records. Comparison was made between patients with EON and those without EON to identify possible risk factors. Ophthalmic outcomes were characterized.

Results

Among 4,141 patients who received ethambutol for TB treatment, 1,062 had an ophthalmology encounter, and 20 (0.5% overall, 1.88% with ophthalmology encounters) developed EON. In unadjusted analysis, compared to patients without EON, those with EON had a similar daily dose, but longer duration of ethambutol treatment (P=0.02). They were older (mean 43.74 vs. 58.60 years, P=0.001), more likely to have hypertension (P=0.02) and smoke (p=0.01). There were no differences in gender, body mass index, diabetes, dyslipidemia, HIV infection or glomerular filtration rate. The peripapillary retinal nerve fiber layer, ganglion cell analysis, and vascular density as measured using retinal optical coherence tomography were impacted by EON. In adjusted logistic regression analysis, age greater than 60 (OR = 8.71, p = 0.01) and smoking (OR = 7.06, p = 0.01) were independent risk factors for EON.

Conclusion

In patients treated with ethambutol, the incidence proportion of EON was 0.5% among those with ethambutol administered and 1.88% among those with ethambutol and an eye visit. Potential EON risk factors were age, hypertension, smoking, and duration of ethambutol medication. Smoking has not been associated with EON in prior studies.
Hidden in plain sight: How helminths manage to thrive in host blood
Authors: Dagenais Maude , Tritten Lucienne
Published: March 2023

Parasitic helminths have evolved a plethora of elegant stratagems to regulate and evade the host immune system, contributing to their considerable persistence and longevity in their vertebrate hosts. Various mechanisms to achieve this state have been described, ranging from interfering with or actively modulating host immune responses to hiding from immune recognition. Because they damage surrounding vessels and disturb blood flow, blood-borne and blood-feeding parasites in particular must deal with much more than immune effector cells. Management of the host complement system and coagulation cascade, as well as the development of processes of hiding and masking, represent hallmarks of life in blood. Here we review recent findings on putative evasion strategies employed by blood-borne parasitic helminths, focusing on the interaction with and utilisation of host serum components by nematodes and trematodes.
Change of metformin concentrations in the liver as a pharmacological target site of metformin after long-term combined treatment with ginseng berry extract
Authors: Lee Choong Whan , You Byoung Hoon , Yim Sreymom , Han Seung Yon , Chae Hee-Sung , Bae Mingoo , Kim Seo-Yeon , Yu Jeong-Eun , Jung Jieun , Nhoek Piseth , Kim Hojun , Choi Han Seok , Chin Young-Won , Kim Hyun Woo , Choi Young Hee
Published: March 2023

Metformin as an oral glucose-lowering drug is used to treat type 2 diabetic mellitus. Considering the relatively high incidence of cardiovascular complications and other metabolic diseases in diabetic mellitus patients, a combination of metformin plus herbal supplements is a preferrable way to improve the therapeutic outcomes of metformin. Ginseng berry, the fruit of Panax ginseng Meyer, has investigated as a candidate in metformin combination mainly due to its anti-hyperglycemic, anti-hyperlipidemic, anti-obesity, anti-hepatic steatosis and anti-inflammatory effects. Moreover, the pharmacokinetic interaction of metformin via OCTs and MATEs leads to changes in the efficacy and/or toxicity of metformin. Thus, we assessed how ginseng berry extract (GB) affects metformin pharmacokinetics in mice, specially focusing on the effect of the treatment period (i.e., 1-day and 28-day) of GB on metformin pharmacokinetics. In 1-day and 28-day co-treatment of metformin and GB, GB did not affect renal excretion as a main elimination route of metformin and GB therefore did not change the systemic exposure of metformin. Interestingly, 28-day co-treatment of GB increased metformin concentration in the livers (i.e., 37.3, 59.3% and 60.9% increases versus 1-day metformin, 1-day metformin plus GB and 28-day metformin groups, respectively). This was probably due to the increased metformin uptake via OCT1 and decreased metformin biliary excretion via MATE1 in the livers. These results suggest that co-treatment of GB for 28 days (i.e., long-term combined treatment of GB) enhanced metformin concentration in the liver as a pharmacological target tissue of metformin. However, GB showed a negligible impact on the systemic exposure of metformin in relation to its toxicity (i.e., renal and plasma concentrations of metformin).
Do global geopolitical risks affect connectedness of global stock market contagion network? Evidence from quantile-on-quantile regression
Authors: Lai Fujun , Li Sicheng , Lv Liang , Zhu Sha
Published: March 2023

Based on the Vector Autoregressive Model (VAR), this paper constructs a contagion complex network of global stock market returns, and uses the Quantile-on-Quantile Regression (QQR) to explore the impact of global geopolitical risks on the connectedness of global stock markets. By applying the risk contagion analysis framework, we depict risk contagion and correlation between financial markets in different countries. We also identify the risk contagion characteristics of international financial markets. This paper innovatively introduces the quantile-on-quantile regression method to the study of geopolitical risk. Through the quantile-on-quantile approach, we find that there is an asymmetric relationship between geopolitical risk and the global stock market correlation network. Our conclusions provide some suggestions for policy makers and relevant investors on how to deal with the current high global geopolitical risks. They also provide ideas on how to effectively hedge such risks during asset allocation and policy formulation.
Predicting benzodiazepine prescriptions: A proof-of-concept machine learning approach
Authors: Kinney Kerry L. , Zheng Yufeng , Morris Matthew C. , Schumacher Julie A. , Bhardwaj Saurabh B. , Rowlett James K.
Published: March 2023

Introduction

Benzodiazepines are the most commonly prescribed psychotropic medications, but they may place users at risk of serious adverse effects. Developing a method to predict benzodiazepine prescriptions could assist in prevention efforts.

Methods

The present study applies machine learning methods to de-identified electronic health record data, in order to develop algorithms for predicting benzodiazepine prescription receipt (yes/no) and number of benzodiazepine prescriptions (0, 1, 2+) at a given encounter. Support-vector machine (SVM) and random forest (RF) approaches were applied to outpatient psychiatry, family medicine, and geriatric medicine data from a large academic medical center. The training sample comprised encounters taking place between January 2020 and December 2021 (N = 204,723 encounters); the testing sample comprised data from encounters taking place between January and March 2022 (N = 28,631 encounters). The following empirically-supported features were evaluated: anxiety and sleep disorders (primary anxiety diagnosis, any anxiety diagnosis, primary sleep diagnosis, any sleep diagnosis), demographic characteristics (age, gender, race), medications (opioid prescription, number of opioid prescriptions, antidepressant prescription, antipsychotic prescription), other clinical variables (mood disorder, psychotic disorder, neurocognitive disorder, prescriber specialty), and insurance status (any insurance, type of insurance). We took a step-wise approach to developing a prediction model, wherein Model 1 included only anxiety and sleep diagnoses, and each subsequent model included an additional group of features.

Results

For predicting benzodiazepine prescription receipt (yes/no), all models showed good to excellent overall accuracy and area under the receiver operating characteristic curve (AUC) for both SVM (Accuracy = 0.868–0.883; AUC = 0.864–0.924) and RF (Accuracy = 0.860–0.887; AUC = 0.877–0.953). Overall accuracy was also high for predicting number of benzodiazepine prescriptions (0, 1, 2+) for both SVM (Accuracy = 0.861–0.877) and RF (Accuracy = 0.846–0.878).

Discussion

Results suggest SVM and RF algorithms can accurately classify individuals who receive a benzodiazepine prescription and can separate patients by the number of benzodiazepine prescriptions received at a given encounter. If replicated, these predictive models could inform system-level interventions to reduce the public health burden of benzodiazepines.
Impacts of recreational cannabis legalization on use and harms: A narrative review of sex/gender differences
Authors: Matheson Justin , Le Foll Bernard
Published: March 2023

Legalization of cannabis use for non-medical (recreational) purposes is changing the global cannabis landscape. As attitudes toward cannabis use become more positive and prevalence of use increases in complex ways, concerns emerge about the potential for increased cannabis-attributable harms. Understanding the who, why, and when of this likely increase in cannabis-attributable harms is thus an important public health priority. Both sex and gender contribute to variability in the use, effects, and harms of cannabis and thus sex/gender considerations are important when evaluating the impacts of cannabis legalization. The goal of this narrative review is to broadly discuss sex/gender differences in attitudes toward and prevalence of cannabis use, whether there are sex/gender differences in the impacts of cannabis legalization, and why these sex/gender differences might exist. One of our strongest conclusions is that men have always been more likely to use cannabis than women, yet the sex/gender gap in prevalence of cannabis use has narrowed over time, and this might be partly due to cannabis legalization. The existing evidence suggests that there have also been sex/gender differences in the impacts of legalization on cannabis-attributable harms such as cannabis-involved motor vehicle collisions and hospitalizations, though these results are more variable. The body of literature reviewed has focused almost exclusively on samples of cisgender research participants, and thus future research should encourage inclusion of transgender and gender-diverse participants. More consideration of sex- and gender-based analysis in research evaluating long-term impacts of cannabis legalization is a clear research priority.