bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous coronary artery dissection in women in the generative period: clinical characteristics, treatment, and outcome—a systematic review and meta-analysis
Authors: Apostolović Svetlana , Ignjatović Aleksandra , Stanojević Dragana , Radojković Danijela Djordjević , Nikolić Miroslav , Milošević Jelena , Filipović Tamara , Kostić Katarina , Miljković Ivana , Djoković Aleksandra , Krljanac Gordana , Mehmedbegović Zlatko , Ilić Ivan , Aleksandrić Srdjan , Paradies Valeria
Published: February 2024

Introduction

Spontaneous coronary artery dissection (SCAD) is a non-traumatic and non-iatrogenic separation of the coronary arterial wall.

Materials and methods

This systematic review and meta-analysis is reported following the PRISMA guidelines and is registered in the PROSPERO database. A literature search was focused on female patients in generative period (16–55 of age) with acute coronary syndrome (ACS) caused by SCAD, and comparison from that database NP-SCAD (spontaneous coronary artery dissection in non pregnant women) and P-SCAD (spontaneous coronary artery dissection in pregnant women).

Results

14 studies with 2,145 females in the generative period with ACS caused by SCAD were analyzed. The median age was 41 years (33.4–52.3 years). The most common risk factor was previous smoking history in 24.9% cases. The most common clinical presentation of ACS was STEMI in 47.4%. Conservative treatment was reported in 41.1%. PCI was performed in 32.7%, and 3.8% of patients had CABG surgery. LAD was the most frequently affected (50.5%). The prevalence of composite clinical outcomes including mortality, non-fatal MI and recurrent SCAD was 3.3% (95% CI: 1.4–5.1), 37.7% (95% CI: 1.9–73.4) and 15.2% (95% CI: 9.1–21.3) of patients. P-SCAD compared to NP-SCAD patients more frequently had STEMI (OR = 3.16; 95% CI: 2.30–4.34;I2 = 64%); with the left main and LAD more frequently affected [(OR = 14.34; 95% CI: 7.71–26.67;I2 = 54%) and (OR = 1.57; 95% CI: 1.06–2.32;I2 = 23%)]; P-SCAD patients more frequently underwent CABG surgery (OR = 6.29; 95% CI: 4.08–9.70;I2 = 0%). NP-SCAD compared to P-SCAD patients were more frequently treated conservatevly (OR = 0.61; 95% CI: 0.37–0.98;I2 = 0%). In P-SCAD compared to NP-SCAD mortality rates (OR = 1.13; 95% CI: 0.06–21.16;I2 = not applicable) and reccurence of coronary artery dissection (OR = 2.54; 95% CI: 0.97–6.61;I2 = 0%) were not more prevalent.

Conclusion

The results of this meta-analysis indicated that patients with P-SCAD more frequently had STEMI, and events more frequently involved left main and LAD compared to NP-SCAD patients. Women with NP-SCAD were significantly more often treated conservatively compared to P-SCAD patients. P-SCAD compared to NP-SCAD patients did not have significantly higher mortality rates or recurrent coronary dissection.
Dynamic arterial elastance as a predictor of arterial pressure response to norepinephrine weaning in mechanically ventilated patients with vasoplegic syndrome—a systematic review and meta-analysis
Authors: Zhou Xiaoyang , Hu Caibao , Pan Jianneng , Xu Chang , Xu Zhaojun , Pan Tao , Chen Bixin
Published: February 2024

Introduction

During the de-escalation phase of circulatory shock, norepinephrine weaning may induce diverse arterial pressure responses in patients with different vasomotor tones. Dynamic arterial elastance (Eadyn) has been extensively studied to predict the arterial pressure response to interventions. We conducted this meta-analysis to systematically assess the predictive performance of Eadyn for the mean arterial pressure (MAP) response to norepinephrine weaning in mechanically ventilated patients with vasoplegic syndrome.

Materials and methods

A systematic literature search was conducted on May 29, 2023 (updated on January 21, 2024), to identify relevant studies from electronic databases. The area under the hierarchical summary receiver operating characteristic curve (AUHSROC) was estimated as the primary measure of diagnostic accuracy because of the varied thresholds reported. Additionally, we observed the distribution of the cutoff values of Eadyn, while computing the optimal value and its corresponding 95% confidential interval (CI).

Results

A total of 5 prospective studies met eligibility, comprising 183 participants, of whom 67 (37%) were MAP responders. Eadyn possessed an excellent ability to predict the MAP response to norepinephrine weaning in patients with vasoplegic syndrome, with an AUHSROC of 0.93 (95% CI: 0.91–0.95), a pooled sensitivity of 0.94 (95% CI: 0.85–0.98), a pooled specificity of 0.73 (95% CI: 0.65–0.81), and a pooled diagnostic odds ratio of 32.4 (95% CI: 11.7–89.9). The cutoff values of Eadyn presented a nearly conically symmetrical distribution; the mean and median cutoff values were 0.89 (95% CI: 0.80–0.98) and 0.90 (95% CI: not estimable), respectively.

Conclusions

This meta-analysis with limited evidences demonstrates that Eadyn may be a reliable predictor of the MAP response to norepinephrine weaning in mechanically ventilated patients with vasoplegic syndrome.

Systematic Review Registration

PROSPERO CRD42023430362.
B-lines by lung ultrasound as a predictor of re-intubation in mechanically ventilated patients with heart failure
Authors: Hyun Junho , Kim Ah-ram , Lee Sang Eun , Kim Min-Seok
Published: February 2024

Introduction

There have been few studies on predictors of weaning failure from MV in patients with heart failure (HF). We sought to investigate the predictive value of B-lines measured by lung ultrasound (LUS) on the risk of weaning failure from mechanical ventilation (MV) and in-hospital outcomes.

Methods

This was a single-center, prospective observational study that included HF patients who were on invasive MV. LUS was performed immediate before ventilator weaning. A positive LUS exam was defined as the observation of two or more regions that had three or more count of B-lines located bilaterally on the thorax. The primary outcome was early MV weaning failure, defined as re-intubation within 72 h.

Results

A total of 146 consecutive patients (mean age 70 years; 65.8% male) were enrolled. The total count of B-lines was a median of 10 and correlated with NT-pro-BNP level (r2 = 0.132, p < 0.001). Early weaning failure was significantly higher in the positive LUS group (9 out of 64, 14.1%) than the negative LUS group (2 out of 82, 2.4%) (p = 0.011). The rate of total re-intubation during the hospital stay (p = 0.004), duration of intensive care unit stay (p = 0.004), and hospital stay (p = 0.010) were greater in the positive LUS group. The negative predictive value (NPV) of positive LUS was 97.6% for the primary outcome.

Conclusion

B-lines measured by LUS can predict the risk of weaning failure. Considering the high NPV of positive LUS, it may help guide the decision of weaning in patients on invasive MV due to acute decompensated HF.
Validity of student evaluation of teaching in higher education: a systematic review
Authors: Quansah Frank , Cobbinah Andrews , Asamoah-Gyimah Kenneth , Hagan John Elvis
Published: February 2024

Introduction

Data obtained from students regarding the quality of teaching are used by higher education administrators to inform decisions concerning tenure, promotion, course development and instructional modifications, among others. This article provides a review regarding studies conducted to examine the validity of student evaluation of teaching, specifically focusing on the following objectives: (1) identify the context where studies have been conducted on student evaluation of teaching; (2) find out the methodologies usually employed for assessing the validity of student evaluation of teaching; and (3) establish the sources of measurement error in student evaluation of teaching.

Methods

The systematic review was conducted based on the PRISMA checklist. The databases searched include Scopus, Web of Science (WoS), Google Scholar, PubMed, MEDLINE, ERIC, JSTOR, PsycLIT, EconLit, APA PsycINFO and EBSCO using some specific keywords. After applying the four eligibility criteria, 15 papers were left to be analyzed.

Results

It was discovered that the generalizability theory approach was mostly used to understand the validity of student evaluation data. The review revealed that students were found at the centre of inconsistencies in the evaluation process.

Discussion

The general impression from the review is that the credibility and validity of teaching evaluation outcomes is questionable, considering the several sources of errors revealed. The study recommended closely studying these sources of errors (e.g., rating behaviours of students).
COPD and T2DM: a Mendelian randomization study
Authors: Wang Tao , Li Jinshuai , Huang Chun , Wu Xiangjian , Fu Xiaoyan , Yang Chunfeng , Li Minfang , Chen Sheng
Published: February 2024

Introduction

Type 2 diabetes (T2DM) stands as a global chronic illness, exerting a profound impact on health due to its complications and generating a significant economic burden. Recently, observational studies have pointed toward a potential link between Chronic Obstructive Pulmonary Disease (COPD) and T2DM. To elucidate this causal connection, we employed the Mendelian randomization analysis.

Method

Our study involved a two-sample Mendelian randomization (MR) analysis on COPD and T2DM. Additionally, tests for heterogeneity and horizontal pleiotropy were performed.

Results

For the MR analysis, 26 independent single nucleotides polymorphisms (SNPs) with strong associations to COPD were chosen as instrumental variables. Our findings suggest a pronounced causal relationship between COPD and T2DM. Specifically, COPD emerges as a risk factor for T2DM, with an odds ratio (OR) of 1.06 and a 95% confidence interval ranging from 1.01 to 1.11 (P = 0.006). Notably, all results were devoid of any heterogeneity or pleiotropy.

Conclusion

The MR analysis underscores a significant causal relationship between COPD and T2DM, highlighting COPD as a prominent risk factor for T2DM.
Normal triglyceride concentration and the risk of diabetes mellitus type 2 in the general population of China
Authors: Guo Rubing , Wei Lianhua , Cao Yongtong , Zhao Wei
Published: February 2024

Introduction

Hypertriglyceridemia and its derivatives are independent predictors of diabetes mellitus type 2 (T2DM). However, the relationship between triglyceride concentrations within the normal range and the incidence of T2DM remains to be clarified. This study investigated the potential relationship between variations in plasma triglyceride levels within the normal range and T2DM onset using data from a longitudinal study of health and retirement in China.

Methods

Between, 2010 and, 2016, we conducted a retrospective cohort study involving 36,441 individuals with normal triglyceride levels. Using a Cox proportional hazards regression model, we examined the connection between normal triglyceride levels and T2DM incidence. We employed this method with smooth curve fitting to investigate potential nonlinear associations. Subgroup analyses were performed based on age, sex, body mass index, smoking and drinking status, hypertension, and family history of diabetes.

Results

A significant linear relationship was observed between normal triglyceride levels and the incidence of T2DM. The hazard ratio for T2DM in individuals with normal triglycerides was 1.81 (95% confidence interval: 1.39, 2.36); P<0.001). Kaplan–Meier analysis further demonstrated a prospective association between the higher tertiles of normal triglyceride levels and the development of T2DM (P<0.001). Subgroup analysis revealed a stronger positive correlation between normal triglyceride levels in females and the risk of T2DM.

Discussion

An increase in triglyceride levels within the normal range is related to a continuous increase in the incidence of T2DM in the general population. These findings show that almost everyone can benefit from reducing triglyceride levels, further emphasizing the importance of lifestyle changes in the general population.
Case report: Complete restoration of the HPA axis function in Cushing’s disease with drug treatment
Authors: Nguyen Joanne Thanh-Tâm , Ferrière Amandine , Tabarin Antoine
Published: February 2024

This report describes a rare case of a 20-year-old man with an ACTH- and prolactin-secreting invasive pituitary macroadenoma causing hyperprolactinemia and Cushing’s disease. He was later found to have an AIP mutation. Treatment with cabergoline (1.5 mg weekly) normalized prolactin concentrations and induced a major shrinkage of the adenoma. Not only was urinary free cortisol normalized for more than 14 years, but also the treatment induced normal hypothalamo-pituitary-adrenal (HPA) axis function as illustrated by the reappearance of a normal cortisol/ACTH circadian rhythm, cortisol suppression to dexamethasone, and disappearance of the excessive and aberrant responses to CRH and desmopressin, respectively. This case is the first description of complete restoration of the physiological characteristics of the HPA axis by a medication during the treatment of Cushing’s disease. Although exceptional, it illustrates that drugs targeting the pituitary adenoma can bring true complete remission of Cushing’s disease.
Clinical characteristics and degree of cardiovascular risk factor control in patients with newly-diagnosed type 2 diabetes in Catalonia
Authors: Ramírez-Morros Anna , Franch-Nadal Josep , Real Jordi , Miró-Catalina Queralt , Bundó Magdalena , Vlacho Bogdan , Mauricio Didac
Published: February 2024

Introduction

Women with type 2 diabetes mellitus (T2DM) face a greater risk of cardiovascular disease (CVD) and encounter challenges in managing cardiovascular risk factors (CVRF); however, limited data are available in individuals with newlydiagnosed T2DM.

Methods

This study aimed to examine differences between women and men at the onset of T2DM in terms of clinical characteristics, glycaemic status, and CVRF management. This was a retrospective cohort study including subjects with newly-diagnosed T2DM from the System for the Development of Research in Primary Care (SIDIAP) database in Catalonia (Spain). Sex differences (Dif) were assessed at baseline and 1-year post-diagnosis, by calculating the absolute difference of means or proportions.

Results

A total of 13,629 subjects with newly-diagnosed T2DM were analyzed. Women were older and had a higher BMI than men. At baseline, women had higher total cholesterol [Dif (95%CI) 10 mg/dL (9.1/10.8)] and low-density lipoprotein cholesterol (LDL-c) [Dif (95%CI) 7 mg/dL (6.3/7.7)], while men had higher rates of smoking and alcohol intake. Lipid target achievement was lower in women, in both primary prevention (LDL-c < 100 mg/dL) [Dif (95%CI) -7.3 mg/dL (-10.5/-4.1)] and secondary prevention (LDL-c < 70 mg/dL) [Dif (95%CI) -8.3 mg/dL (-17.3/0.7)], along with lower statin and antiplatelet prescriptions, especially one year after diagnosis. Changes in clinical and laboratory data one year post-diagnosis revealed that, in the primary prevention group, men experienced greater improvements in total cholesterol, LDL-c and triglycerides, while women had less success in achieving CVRF control targets compared to men. Additionally, cardiovascular events, such as coronary artery disease and peripheral artery disease increased more in men than in women within the first year of diagnosis, especially in primary prevention subjects.

Conclusion

Differences between men and women CVRF are already apparent at the onset of T2DM, particularly in primary prevention, with notable differences in lipid profile and target level attainment.
Advances in risk predictive performance of pre-symptomatic type 1 diabetes via the multiplex Antibody-Detection-by-Agglutination-PCR assay
Authors: Tandel Devangkumar , Hinton Brigette , de Jesus Cortez Felipe , Seftel David , Robinson Peter , Tsai Cheng-ting
Published: February 2024

Introduction

Achieving early diagnosis of pre-symptomatic type 1 diabetes is critical to reduce potentially life-threatening diabetic ketoacidosis (DKA) at symptom onset, link patients to FDA approved therapeutics that can delay disease progression and support novel interventional drugs development. The presence of two or more islet autoantibodies in pre-symptomatic type 1 diabetes patients indicates high-risk of progression to clinical manifestation.

Method

Herein, we characterized the capability of multiplex ADAP assay to predict type 1 diabetes progression. We obtained retrospective coded sera from a cohort of 48 progressors and 44 non-progressors from the NIDDK DPT-1 study.

Result

The multiplex ADAP assay and radiobinding assays had positive predictive value (PPV)/negative predictive value (NPV) of 68%/92% and 67%/66% respectively. The improved NPV stemmed from 12 progressors tested positive for multiple islet autoantibodies by multiplex ADAP assay but not by RBA. Furthermore, 6 out of these 12 patients tested positive for multiple islet autoantibodies by RBA in subsequent sampling events with a median delay of 2.8 years compared to multiplex ADAP assay.

Discussion

In summary, multiplex ADAP assay could be an ideal tool for type 1 diabetes risk testing due to its sample-sparing nature (4µL), non-radioactiveness, compatibility with widely available real-time qPCR instruments and favorable risk prediction capability.
Transient synchronization stability of photovoltaics integration by singular perturbation analysis
Authors: Wu Jiaqi , Han Miao , Zhan Meng
Published: February 2024

The integration of large-scale photovoltaics (PVs) into the power grid has significantly altered the transient synchronization dynamics of traditional power systems dominated by synchronous generators (SGs) and posed great challenges to modeling and analysis of PVs integration. In this paper, the transient synchronization stability of the PV-SG system is studied using the singular perturbation technique. Firstly, a nonlinear model of a PV-SG system is established to reveal the multiscale transient synchronization characteristics. Further, the full system is decomposed into a slow subsystem and a fast subsystem by the singular perturbation technique. The fast subsystem containing the dynamics of the DC voltage control, terminal voltage control, and phase-locked loop, and the slow subsystem containing the dynamics of rotor motion can perfectly reflect the dynamics of the full system within the electromagnetic and electromechanical timescales, respectively. The proposed model provides a clearer physical picture of dynamics in the PV-SG system within the electromagnetic and electromechanical timescales. Subsequently, the stability of the slow and fast subsystems is investigated using the energy function and eigenvalue analysis methods, respectively. Meanwhile, the impacts of various operating, control, and structural parameters on the transient synchronization stability are uncovered. Different from the most existing research endeavors on the wide simulations of the PVs integration, the impact of PVs on the synchronization dynamics of SGs without considering the dynamical characteristics of the PV system, and the transient synchronization stability analyses of the PLL-based voltage source converter systems, it is the key contribution to study the transient synchronization dynamical characteristics of the PV system and its interaction with the SG under different timescales. All these are helpful and easy to extend to more complicated PV-SG systems. Finally, the analysis results are validated by extensive simulations.
A MYH7 variant in a five-generation-family with hypertrophic cardiomyopathy
Authors: Franke Magda , Książczyk Tomasz Marcin , Dux Marta , Chmielewski Przemysław , Truszkowska Grażyna , Czapczak Dorota , Pietrzak Radosław , Bilinska Zofia Teresa , Demkow Urszula , Werner Bożena
Published: February 2024

Background: Hypertrophic cardiomyopathy (HCM) is a genetic condition with a prevalence of 1:500–1:3 000. Variants in genes encoding sarcomeric proteins are mainly responsible for the disease. MYH7 gene encoding a myosin heavy chain beta, together with MYPBC3 gene are the two most commonly affected genes. The clinical presentation of this disease varies widely between individuals. This study aims to report a variant of MYH7 responsible for HCM in a five-generation family with a history of cardiac problems.

Methods: The diagnosis was established according to the European Society of Cardiology HCM criteria based on two-dimensional Doppler echocardiography or cardiovascular magnetic resonance. Genetic analysis was performed using next-generation-sequencing and Sanger method.

Results: The medical history of the presented family began with a prenatal diagnosis of HCM in the first child of a family with previously healthy parents. Five generations of the family had a long history of sudden cardiac death and cardiac problems. A NM_000257.4:c.2342T>A (p.Leu781Gln) variant was detected in the MYH7 gene. It was heterozygous in the proband and in all affected individuals in a large family. The variant was present in 10 affected members of the family, and was absent in 7 members. The clinical course of the disease was severe in several members of the family: three family members died of sudden cardiac death, one patient required heart transplantation, three underwent septal myectomy, and three required implantable cardioverter defibrillator (ICD) implantation.

Conclusion: Herein, we report a MYH7 variant responsible for HCM. Familial HCM is inherited primarily in autosomal dominant mode, which is in accordance with our study. However, the presented family showed a broad clinical spectrum of HCM. Out of 10 family members with positive genetic testing 8 had severe presentation of the disease and 2 had a mild phenotype. This suggests that the severity of the disease may depend on other factors, most likely genetic.
Immune checkpoint ligands expressed on mature high endothelial venules predict poor prognosis of NSCLC: have a relationship with CD8+ T lymphocytes infiltration
Authors: Luo Jing , Shi Xiuhuan , Liu Yumeng , Wang Jian , Wang Hao , Yang Xuena , Sun Qian , Hui Zhenzhen , Wei Feng , Ren Xiubao , Zhao Hua
Published: February 2024

Background

An insufficient number of intratumoral CD8+ T lymphocytes is a major barrier to antitumor immunity and immunotherapy. High endothelial venules (HEVs) are the major sites through which lymphocytes enter tumors; however, the molecular mechanism through which HEVs mediate CD8+ T lymphocyte infiltration remains poorly understood.

Methods

Forty-two patients with stage IIIA lung adenocarcinoma, who underwent surgery, were recruited. Multiplex immunohistochemical staining was conducted on tumor tissues to detect the immune checkpoint ligands (ICLs) expressed in the HEVs, blood vessels, and lymphatics. A new ICL score model was constructed to evaluate ligand expression. The relationship between ICL score, tumor-infiltrating CD8+ T cell frequency, and survival of patients was investigated.

Results

Mature HEVs, but not blood vessels or lymphatics, mediated CD8+ T cell infiltration. However, the ICLs expressed on mature HEVs could negatively regulate CD8+ T cell entry into tertiary lymphoid structures (TLSs). In addition, according to the results obtained using our ICLtotal score model, the expression of ICLs on HEVs was observed to be a predictor of both CD8+ T cell infiltration and survival, in which a high ICLtotal score > 1 represent a weak CD8+ T cell infiltration and a high ICLtotal score > 2 predicts poor survival.

Conclusion

Using the ICL score model, we discovered that ICLs expressed on HEVs are indicative of CD8+ T cell subset infiltration in TLSs, as well as of patient survival with lung cancer.
Causal association between the peripheral immunity and the risk and disease severity of multiple sclerosis
Authors: Chen Lian , Zhu Li-Fang , Zhang Lu-Yang , Chu Yun-Hui , Dong Ming-Hao , Pang Xiao-Wei , Yang Sheng , Zhou Luo-Qi , Shang Ke , Xiao Jun , Wang Wei , Qin Chuan , Tian Dai-Shi
Published: February 2024

Background

Growing evidence links immunological responses to Multiple sclerosis (MS), but specific immune factors are still unclear.

Methods

Mendelian randomization (MR) was performed to investigate the association between peripheral hematological traits, MS risk, and its severity. Then, further subgroup analysis of immune counts and circulating cytokines and growth factors were performed.

Results

MR revealed higher white blood cell count (OR [95%CI] = 1.26 [1.10,1.44], P = 1.12E-03, P adjust = 3.35E-03) and lymphocyte count (OR [95%CI] = 1.31 [1.15,1.50], P = 5.37E-05, P adjust = 3.22E-04) increased the risk of MS. In further analysis, higher T cell absolute count (OR [95%CI] = 2.04 [1.36,3.08], P = 6.37E-04, P adjust = 2.19E-02) and CD4+ T cell absolute count (OR [95%CI] = 2.11 [1.37,3.24], P = 6.37E-04, P adjust = 2.19E-02), could increase MS risk. While increasing CD25++CD4+ T cell absolute count (OR [95%CI] = 0.75 [0.66,0.86], P = 2.12E-05, P adjust = 1.72E-03), CD25++CD4+ T cell in T cell (OR [95%CI] = 0.79[0.70,0.89], P = 8.54E-05, P adjust = 5.29E-03), CD25++CD4+ T cell in CD4+ T cell (OR [95%CI] = 0.80[0.72,0.89], P = 1.85E-05, P adjust = 1.72E-03), and CD25++CD8+ T cell in T cell (OR [95%CI] = 0.68[0.57,0.81], P = 2.22E-05, P adjust = 1.72E-03), were proved to be causally defensive for MS. For the disease severity, the suggestive association between some traits related to CD4+ T cell, Tregs and MS severity were demonstrated. Moreover, elevated levels of IL-2Ra had a detrimental effect on the risk of MS (OR [95%CI] = 1.22 [1.12,1.32], P = 3.20E-06, P adjust = 1.34E-04).

Conclusions

This study demonstrated a genetically predicted causal relationship between elevated peripheral immune cell counts and MS. Subgroup analysis revealed a specific contribution of peripheral immune cells, holding potential for further investigations into the underlying mechanisms of MS and its severity.
Oriented display of HIV-1 Env trimers by a novel coupling strategy enhances B cell activation and phagocytosis
Authors: Di Vincenzo Riccardo , Beutel Jannis , Arnold Philipp , Wang Yu , Damm Dominik , Tannig Pierre , Lux Anja , Temchura Vladimir , Eichler Jutta , Überla Klaus
Published: February 2024

Introduction

Conformationally stabilized Env trimers have been developed as antigens for the induction of neutralizing antibodies against HIV-1. However, the non-glycosylated immunodominant base of these soluble antigens may compete with the neutralizing antibody response. This has prompted attempts to couple Env trimers to organic or inorganic nanoparticles with the base facing towards the carrier. Such a site-directed coupling could not only occlude the base of the trimer, but also enhance B cell activation by repetitive display.

Methods

To explore the effect of an ordered display of HIV-1 Env on microspheres on the activation of Env-specific B cells we used Bind&Bite, a novel covalent coupling approach for conformationally sensitive antigens based on heterodimeric coiled-coil peptides. By engineering a trimeric HIV-1 Env protein with a basic 21-aa peptide (Peptide K) extension at the C-terminus, we were able to covalently biotinylate the antigen in a site-directed fashion using an acidic complementary peptide (Peptide E) bearing a reactive site and a biotin molecule. This allowed us to load our antigen onto streptavidin beads in an oriented manner.

Results

Microspheres coated with HIV-1 Env through our Bind&Bite system showed i) enhanced binding by conformational anti-HIV Env broadly neutralizing antibodies (bNAbs), ii) reduced binding activity by antibodies directed towards the base of Env, iii) higher Env-specific B cell activation, and iv) were taken-up more efficiently after opsonization compared to beads presenting HIV-1 Env in an undirected orientation.

Discussion

In comparison to site-directed biotinylation via the Avi-tag, Bind&Bite, offers greater flexibility with regard to alternative covalent protein modifications, allowing selective modification of multiple proteins via orthogonal coiled-coil peptide pairs. Thus, the Bind&Bite coupling approach via peptide K and peptide E described in this study offers a valuable tool for nanoparticle vaccine design where surface conjugation of correctly folded antigens is required.
Single-cell and Bulk RNA-Seq reveal angiogenic heterogeneity and microenvironmental features to evaluate prognosis and therapeutic response in lung adenocarcinoma
Authors: Tang Lijuan , Chen Zhike , Yang Jian , Li Qifan , Wang Sichu , Mo Taoming , Zeng Weibiao , Ding Hao , Pan Shu
Published: February 2024

Background

Angiogenesis stands as a pivotal hallmark in lung adenocarcinoma (LUAD), intricately shaping the tumor microenvironment (TME) and influencing LUAD progression. It emerges as a promising therapeutic target for LUAD, affecting patients’ prognosis. However, its role in TME, LUAD prognosis, and its clinical applicability remain shrouded in mystery.

Methods

We employed integrated single-cell and bulk transcriptome sequencing to unravel the heterogeneity of angiogenesis within LUAD cells. Through “consensus clustering”, we delineated distinct angiogenic clusters and deciphered their TME features. “Monocle2” was used to unravel divergent trajectories within malignant cell subpopulations of LUAD. Additionally, regulon submodules and specific cellular communication patterns of cells in different angiogenic states were analyzed by “pyscenic” and “Cellchat” algorithms. The “univariate Cox” and “LASSO” algorithms were applied to build angiogenic prognostic models. Immunohistochemistry (IHC) on clinical samples validated the role of model factors in LUAD angiogenesis. We utilized CTRP 2.0 and PRISM databases for pinpointing sensitive drugs against lung adenocarcinoma.

Results

Two clusters for the activation of angiogenesis were identified, with Cluster 1 showing a poor prognosis and a pro-cancerous TME. Three differentiated states of malignant epithelial LUAD cells were identified, which had different degrees of angiogenic activation, were regulated by three different regulon submodules, and had completely different crosstalk from other cells in TME. The experiments validate that SLC2A1 promotes angiogenesis in LUAD. ARS (Angiogenesis related score) had a high prognostic value; low ARSs showed immunotherapy benefits, whereas high ARSs were sensitive to 15 chemotherapeutic agents.

Conclusion

The assessment of angiogenic clusters helps to determine the prognostic and TME characteristics of LUAD. Angiogenic prognostic models can be used to assess the prognosis, immunotherapeutic response, and chemotherapeutic drug sensitivity of LUAD.
Prevalence of a large panel of systemic autoantibodies in the Bavarian adult population
Authors: Rohm Florian , Kling Elisabeth , Hoffmann Reinhard , Meisinger Christine , Linseisen Jakob
Published: February 2024

Objective

Autoimmune diseases commonly feature the presence of specific humoral autoantibodies. However, the prevalence of a large panel of systemic autoantibodies has never been assessed in the general population. We, therefore, described the prevalence of about 50 humoral systemic autoantibodies in a sample of the general Bavarian adult population.

Methods

Non-fasting venous serum samples from 331 participants were analyzed for 7 autoantibody screening tests (nuclear, cytoplasmic, and mitotic ANA, ANCA, cANCA and pANCA, anti-ENA autoantibodies) and 44 different monospecific humoral non-organ specific/systemic autoantibodies using indirect immunofluorescence tests, ELISAs, and line blots. In order to assess associations between sex, age, BMI, education level, smoking status and the presence of systemic autoantibodies, logistic regression analyses were conducted.

Results

At least one screening test was positive in 29.9% of the participants, and 42.3% of the participants were seropositive for at least one monospecific autoantibody. The most frequently found monospecific autoantibodies were rheumatoid factor (35.6%), ß2-glycoprotein 1 IgM (4.8%), and cardiolipin IgG (1.8%). Only few associations between sex, age, BMI, education, smoking status and autoantibody frequencies were observed.

Conclusion

Systemic autoantibodies are common in the general Bavarian population, and largely independent of sex, age, BMI, education, or smoking status. The study results may give orientation to clinicians about the occurrence of autoantibodies in the population, not (yet) associated with clinical symptoms.
Effect of interface treatment on the flexural performance of existing RC bridge beams strengthened with UHPC
Authors: Song Jianping , Li Baojun , Kong Lingcai , Qin Dafan , Zhu Chao , Kuang Yang , Shan Aicheng
Published: February 2024

As one of the most innovative cement-based materials, ultra-high performance concrete (UHPC), with excellent durability and mechanical properties, has been widely used in strengthening existing bridges. In this study, in-situ four-point bending tests were carried out to investigate the flexural behavior of precast reinforced concrete (RC) hollow slab beams in service for 15 years strengthened with UHPC. Among them, three hollow slab beams were strengthened with UHPC, and the interface treatment was chiseling, planting rebars, and a combination of chiseling and planting rebars, respectively. The remaining one without any strengthening treatment was used as the control specimen. To evaluate the enhancement effect of different interface treatments on UHPC-strengthened beams, the cracking load, ultimate load, crack development and failure modes of UHPC-strengthened beams were analyzed. Results indicated that the stiffness, deflection capacity and flexural capacity of UHPC-strengthened beams was significantly improved. Meanwhile, the stiffness of UHPC-strengthened beams in the pre-damage stage was increased by 49%–94%, when compared with the unstrengthened beam. Correspondingly, the ultimate flexural capacity was increased by 29%–38%. The interface chiseling treatment was more favorable to enhance the deformation capacity of UHPC-strengthened beams. The interface planting rebar treatment was more favorable to enhancing the ductility of UHPC-strengthened beams. The crack development was effectively suppressed by the interface chiseling and planting rebars together. This contributes to a higher load capacity reserve for UHPC-strengthened beams. The bearing capacity under serviceability limit state of the UHPC-strengthened beams was increased by 1.25, 2, and 2.5 times through the interface treatments of chiseling, planting rebars, and a combination of both, respectively.
Occupational respiratory disorders in Iran: a review of prevalence and inducers
Authors: Beigoli Sima , Amin Fatemeh , Kazemi Rad Hamideh , Rezaee Ramin , Boskabady Mohammad Hossein
Published: February 2024

The link between occupational respiratory diseases (ORD) and exposure to harmful factors that are present in the workplace has been well shown. Factors such as physical activity, age and duration of occupational exposure playing important roles in ORD severity, should be identified in the workplace, their effects on workers health should be studied, and ultimately, exposure to them must be minimized. We carried out a literature review by searching PubMed, Scopus, and Web of Science databases to retrieve studies published from 1999 until the end of April 2023 reporting the prevalence and inducers of ORD in Iran. In Iranian workers, several ORD such as interstitial lung disease, silicosis, occupational asthma, pulmonary inflammatory diseases, chronic obstructive pulmonary diseases, and lung cancers have been reported. It was indicated that ORD mainly occur due to repeated and prolonged exposure to noxious agents in the workplace. We also extracted the prevalence of ORD in different regions of Iran from the retrieved reports. Based on our literature review, the prevalence of ORD among Iranian workers highlights the importance of regular assessment of the risk of exposure to noxious agents in the workplace to develop measures for preventing potential adverse effects.
Comparison of the immune effects of the Chlamydia abortus MOMP antigen displayed in different parts of bacterial ghosts
Authors: Zhang Huaiyu , Li Zhaocai , Li Wei , Jin Youshun , Li Yunhui , Xiao Qian , Tong Dewen , Zhou Jizhang
Published: February 2024

Bacterial ghosts (BGs) are promising vaccine platforms owing to their high adjuvant properties and delivery efficiency. Heterologous antigens can be anchored to different parts of BGs using genetic engineering strategies to prepare vaccines. However, several key issues need to be resolved, including the efficient preparation of BGs and determining the optimal anchoring position of exogenous antigens in the BGs. Here, we prepared an efficient temperature-controlled lysis system using lysis gene E of phage PhiX174 and used the major outer membrane protein (MOMP) of Chlamydia abortus (C. abortus) as a model antigen to explore the optimal display location of exogenous antigens in BGs. We demonstrated that the constructed recombinant temperature-controlled lysis plasmid can still stably inhibit E gene expression at 37°C, and the lysis efficiency of E. coli can reach above 99.9%. Four recombinant MOMP Escherichia coli (E. coli) ghost vaccines were constructed using different anchor sequences. These vaccines all induced strong specific antibody responses and secrete high levels of IFN-γ in immunized mice and significantly increased the clearance of C. abortus in a mouse infection model. Notably, the strongest immune effect was observed when MOMP was displayed on the surface of E. coli ghosts (rECG-InpN-M), which resulted in the clearance of C. abortus in mice 6 days earlier than that with the recombinant MOMP vaccine. Altogether, we constructed an efficient BG temperature-controlled lysis system and provided a feasible strategy for developing a BG delivery platform with enhanced immune effects.
Differences in molecular characteristics and expression of virulence genes in carbapenem-resistant and sensitive Klebsiella pneumoniae isolates in Ningbo, China
Authors: Jiang Min , Qiu Xuedan , Shui Siyi , Zhao Rongqing , Lu Wenjun , Lin Chenyao , Tu Yanye , Wu Yifeng , Li Qingcao , Wu Qiaoping
Published: February 2024

Background

In recent years, Klebsiella pneumoniae has attracted attention because of its increasing drug resistance. At the same time, the migration and pathogenicity caused by its virulence genes also bring many difficulties to the diagnosis and treatment of clinical infections. However, it is currently unclear whether there are differences in virulence and pathogenicity with changes in drug resistance.

Objective

To understand the differences in molecular characteristics and expression of virulence genes in carbapenem-resistant Klebsiella pneumoniae (CRKP) and carbapenem-sensitive Klebsiella pneumoniae (CSKP).

Methods

Using polymerase chain reaction (PCR), we examined capsule polysaccharide-related genes and virulence genes in 150 clinical isolates of CRKP and 213 isolates of CSKP from the local area in Ningbo, China. Multilocus sequence typing (MLST) was used to analyze the phylogenetic relationships of clinical Klebsiella pneumoniae isolates. Furthermore, real-time quantitative PCR (RT-qPCR) was used to analyze the expression differences of common virulence genes in CSKP and CRKP, and the virulence was further verified by the larval model of Galleria mellonella.

Results

The study found that the detection rates of genes rmpA, iroB, peg-344, magA, aerobactin, alls, kfu, and entB were significantly higher in CSKP compared to CRKP. The capsule gene types K1 and K2 were more common in CSKP, while K5 was more common in CRKP. Hypervirulent Klebsiella pneumoniae (hvKP) was predominantly from CSKP. CRKP strains exhibited noticeable homogeneity, with ST11 being the predominant sequence type among the strains. CSKP strains showed greater diversity in ST types, but ST23 was still the predominant sequence type. Carbapenem-sensitive hypervirulent Klebsiella pneumoniae (CS-hvKP) had higher expression of rmpA and rmpA2 genes compared to carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP). In the wax moth virulence model, the survival rate of CS-hvKP was significantly lower than that of CR-hvKP.

Conclusion

There is a significant difference in the distribution of virulence genes between CSKP and CRKP, with CSKP carrying a significantly greater number of virulence genes. Furthermore, compared to CSKP, CRKP strains exhibit noticeable homogeneity, with ST11 being the predominant sequence type among the strains. Additionally, in terms of virulence gene expression efficiency and virulence, CSKP is significantly higher than CRKP.
Dysautonomia following Lyme disease: a key component of post-treatment Lyme disease syndrome?
Authors: Adler Brittany L. , Chung Tae , Rowe Peter C. , Aucott John
Published: February 2024

Dysautonomia, or dysfunction of the autonomic nervous system (ANS), may occur following an infectious insult and can result in a variety of debilitating, widespread, and often poorly recognized symptoms. Dysautonomia is now widely accepted as a complication of COVID-19 and is an important component of Post-Acute Sequelae of COVID-19 (PASC or long COVID). PASC shares many overlapping clinical features with other infection-associated chronic illnesses including Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Post-Treatment Lyme Disease Syndrome (PTLDS), suggesting that they may share common underlying mechanisms including autonomic dysfunction. Despite the recognition of this complication of Lyme disease in the care of patients with PTLD, there has been a scarcity of research in this field and dysautonomia has not yet been established as a complication of Lyme disease in the medical literature. In this review, we discuss the evidence implicating Borrelia burgdorferi as a cause of dysautonomia and the related symptoms, propose potential pathogenic mechanisms given our knowledge of Lyme disease and mechanisms of PASC and ME/CFS, and discuss the diagnostic evaluation and treatments of dysautonomia. We also outline gaps in the literature and priorities for future research.
Enhancing regeneration and repair of long-distance peripheral nerve defect injuries with continuous microcurrent electrical nerve stimulation
Authors: Kong Junjie , Teng Cheng , Liu Fenglan , Wang Xuzhaoyu , Zhou Yi , Zong Ying , Wan Zixin , Qin Jun , Yu Bin , Mi Daguo , Wang Yaxian
Published: February 2024

Introduction

Peripheral nerve injuries, especially those involving long-distance deficits, pose significant challenges in clinical repair. This study explores the potential of continuous microcurrent electrical nerve stimulation (cMENS) as an adjunctive strategy to promote regeneration and repair in such cases.

Methods

The study initially optimized cMENS parameters and assessed its impact on Schwann cell activity, neurotrophic factor secretion, and the nerve regeneration microenvironment. Subsequently, a rat sciatic nerve defect-bridge repair model was employed to evaluate the reparative effects of cMENS as an adjuvant treatment. Functional recovery was assessed through gait analysis, motor function tests, and nerve conduction assessments. Additionally, nerve regeneration and denervated muscle atrophy were observed through histological examination.

Results

The study identified a 10-day regimen of 100uA microcurrent stimulation as optimal. Evaluation focused on Schwann cell activity and the microenvironment, revealing the positive impact of cMENS on maintaining denervated Schwann cell proliferation and enhancing neurotrophic factor secretion. In the rat model of sciatic nerve defect-bridge repair, cMENS demonstrated superior effects compared to control groups, promoting motor function recovery, nerve conduction, and sensory and motor neuron regeneration. Histological examinations revealed enhanced maturation of regenerated nerve fibers and reduced denervated muscle atrophy.

Discussion

While cMENS shows promise as an adjuvant treatment for long-distance nerve defects, future research should explore extended stimulation durations and potential synergies with tissue engineering grafts to improve outcomes. This study contributes comprehensive evidence supporting the efficacy of cMENS in enhancing peripheral nerve regeneration.
Different reactive profiles of calmodulin in the CSF samples of Chinese patients of four types of genetic prion diseases
Authors: Jia Xiao-Xi , Hu Chao , Chen Cao , Gao Li-Ping , Liang Dong-Lin , Zhou Wei , Cao Run-Dong , Xiao Kang , Shi Qi , Dong Xiao-Ping
Published: February 2024

Background and purpose

Calmodulin (CaM) levels exhibit significant elevation in the brain tissue of rodent and cell line models infected with prion, as well as in the cerebrospinal fluid (CSF) samples from patients diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD). However, the status of CSF CaM in patients with genetic prion diseases (gPrDs) remains unclear. This study aims to assess the characteristics of CSF CaM in Chinese patients presenting four subtypes of gPrDs.

Methods

A total of 103 CSF samples from patients diagnosed with T188K-gCJD, E200K-gCJD, D178N-FFI, P102L-GSS were included in this study, along with 40 CSF samples from patients with non-prion diseases (non-PrDs). The presence of CSF CaM and 14-3-3 proteins was assessed using Western blots analysis, while levels of CSF 14-3-3 and total tau were measured using enzyme-linked immunosorbent assays (ELISAs). Statistical methods including multivariate logistic regression were employed to evaluate the association between CSF CaM positivity and relevant clinical, laboratory, and genetic factors.

Results

The positive rates of CSF CaM were significantly higher in cases of T188K-gCJD (77.1%), E200K-gCJD (86.0%), and P102-GSS (90.9%) compared to non-PrD cases (22.5%). In contrast, CSF CaM positivity was slightly elevated in D178N-FFI (34.3%). CSF CaM positivity was remarkably high in patients who tested positive for CSF 14-3-3 by Western blot and exhibited high levels of total tau (≥1400 pg/ml) as measures by ELISA. Multivariate logistic regression analysis confirmed a significant association between CSF CaM positivity and specific mutations in PRNP, as well as with CSF 14-3-3 positivity. Furthermore, the diagnostic performance of CaM surpassed that of 14-3-3 and tau when analyzing CSF samples from T188K-gCJD and E200K-gCJD patients.

Conclusion

Western blot analysis reveals significant variations in the positivity of CSF CaM among the four genotypes of gPrD cases, demonstrating a positive correlation with 14-3-3 positivity and elevated tau levels in CSF.
Association between dietary intake of vitamin D and risk of depression, anxiety, and sleep disorders among physically active adults: a cross-sectional study
Authors: Arabshahi Vajiheh , Khoddami Mehrad , Milajerdi Maryam , Moabedi Mahdi , Milajerdi Alireza
Published: February 2024

Introduction

Rare studies have been done to investigate the association between dietary intakes of vitamin D and the risk of mental health disorders among athletes. The current study aimed to investigate the association between this vitamin intake and the risk of depression, anxiety, and sleep disorders among a group of Iranian physically active adults.

Methods

This cross-sectional study was conducted among 690 healthy athletes (18–50 years, mean BMI between 20 and 30) in Kashan, Iran. The usual dietary intake of participants was assessed by a 147-item FFQ. Depression was assessed by the Beck Depression Inventory-II (21-item), anxiety by the Beck Anxiety Inventory (21-item), and sleep disorders by the Pittsburgh Sleep Quality Index questionnaires. Statistical analyses were done by using SPSS version 18. p values < 0.05 were considered significant.

Results

No significant association was found between vitamin D dietary intake and risk of depression in the full-adjusted model (OR: 0.96, 95% CI: 0.62, 1.51). In contrast, participants at the highest tertile of vitamin D consumption had a 49% lower risk of anxiety than those at the lowest tertile (OR: 0.51, 95%: 0.29, 0.87). Moreover, a significant 46% lower risk of sleep disorders was found among those with the highest intake of vitamin D in comparison to participants with the lowest intake (OR: 0.54, 95% CI: 0.37, 0.78).

Conclusion

We found a significant association between dietary vitamin D intake and reduced risk of anxiety and sleep disorders, but not with depression, in this study. Further prospective studies are recommended for future investigations.