bluuebunny/crossref_metadata_2025 huggingface dataset:
Are the digit ratio (2D:4D) and hand grip strength related to Parkinson disease in elderly males?
Authors: Arazi Hamid , Birak Olia Roghayeh Bavafa , Eghbali Ehsan
Published: March 2023

Background

Sex hormones affect the pathogenesis of Parkinson patients and it has been suggested that gender is the most important factor in the development and progression of Parkinson’s disease. Studies have shown that the second to fourth digit ratio (2D:4D) is affected by the prenatal testosterone and estrogen levels and can predict predisposition to disease. In addition, decreased muscle strength in people with Parkinson’s has been repeatedly reported. Hand grip strength (HGS) is a suitable measure to evaluate the musculoskeletal system among the elderly and it is considered as an indicator of the overall strength of the body. This study aimed at investigating the relationship between Parkinson’s disease and HGS and 2D:4D ratio.

Methods

In this study 117 elderly men with Parkinson disease (mean age of 61.66 ± 11.28 years) and 156 healthy control subjects (mean age of 61.86 ± 6.29 years) participated. After determining the level of disability of Parkinson patients by a neurologist (level of disability in the range of 1–4), anthropometric indices (height, weight, length of the second and fourth fingers) and maximum HGS were measured.

Results

Although 2D:4D ratios (right and left hand) of male patients with Parkinson’s disease were higher than those of healthy males, this difference was not statistically significant (P = 0.12, P = 0.40; respectively). Conversely, HGS for the right and left hands of Parkinson patients were significantly lower than those of healthy males (P = 0.02, P = 0.03; respectively). The results showed a significant negative relationship between Parkinson disease and the right and left HGS (R = -0.16, P = 0.005; R = -0.17, P = 0.003; respectively). Parkinson disease had no significant relationship with 2D:4D of the right hand, left hand, mean finger ratio and DR−L 2D:4D (P > 0.05). The regression results showed that the right and left HGS were not able to predict Parkinson disease (P = 0.25, P = 0.16; respectively).

Conclusion

We concluded that HGS was negatively associated with the Parkinson disease, but conversely, 2D:4D may not be a valuable biomarker of elevated risk of Parkinson in elderly males.
Effect of a four-week isocaloric ketogenic diet on physical performance at very high-altitude: a pilot study
Authors: Chiarello Nicolas , Leger Bertrand , De Riedmatten Mathieu , Rossier Michel F. , Vuistiner Philippe , Duc Michael , Rapillard Arnaud , Allet Lara
Published: March 2023

Background

A ketogenic diet (KD) reduces daily carbohydrates (CHOs) ingestion by replacing most calories with fat. KD is of increasing interest among athletes because it may increase their maximal oxygen uptake (VO2max), the principal performance limitation at high-altitudes (1500–3500 m). We examined the tolerance of a 4-week isocaloric KD (ICKD) under simulated hypoxia and the possibility of evaluating ICKD performance benefits with a maximal graded exercise bike test under hypoxia and collected data on the effect of the diet on performance markers and arterial blood gases.

Methods

In a randomised single-blind cross-over model, 6 recreational mountaineers (age 24–44 years) completed a 4-week ICKD followed or preceded by a 4-week usual mixed Western-style diet (UD). Performance parameters (VO2max, lactate threshold [LT], peak power [Ppeak]) and arterial blood gases (PaO2, PaCO2, pH, HCO3−) were measured at baseline under two conditions (normoxia and hypoxia) as well as after a 4-week UD and 4-week ICKD under the hypoxic condition.

Results

We analysed data for all 6 participants (BMI 19.9–24.6 kg m−2). Mean VO2max in the normoxic condition was 44.6 ml kg−1 min−1. Hypoxia led to decreased performance in all participants. With the ICKD diet, median values for PaO2 decreased by − 14.5% and VO2max by + 7.3% and Ppeak by + 4.7%.

Conclusion

All participants except one could complete the ICKD. VO2max improved with the ICKD under the hypoxia condition. Therefore, an ICKD is an interesting alternative to CHOs dependency for endurance performance at high-altitudes, including high-altitude training and high-altitude races. Nevertheless, decreased PaO2 with ICKD remains a significant limitation in very-high to extreme altitudes (> 3500 m).

Trial registration Clinical trial registration Nr. NCT05603689 (Clinicaltrials.gov). Ethics approval CER-VD, trial Nr. 2020-00427, registered 18.08.2020—prospectively registered.
Metabolic syndrome biomarkers relate to rate of cognitive decline in MCI and dementia stages of Alzheimer’s disease
Authors: Pillai Jagan A. , Bena James , Bekris Lynn , Kodur Nandan , Kasumov Takhar , Leverenz James B. , Kashyap Sangeeta R. ,   on behalf of the Alzheimer’s Disease Neuroimaging Initiative
Published: March 2023

Background

The relationship between biomarkers of metabolic syndrome and insulin resistance, plasma triglyceride/HDL cholesterol (TG/HDL-C) ratio, on the rate of cognitive decline in mild cognitive impairment (MCI) and dementia stages of Alzheimer’s disease (AD) is unknown. The role of peripheral and cerebrospinal fluid (CSF) levels of Apolipoprotein A1 (ApoA1), a key functional component of HDL, on cognitive decline also remains unclear among them. Here we evaluate baseline plasma TG/HDL-C ratio and CSF and plasma ApoA1 levels and their relation with cognitive decline in the MCI and Dementia stages of AD.

Patients and methods

A retrospective longitudinal study (156 participants; 106 MCI, 50 AD dementia) from the Alzheimer’s Disease Neuroimaging Initiative, with an average of 4.0 (SD 2.8) years follow-up. Baseline plasma TG/HDL-C, plasma, and CSF ApoA1 and their relationship to inflammation and blood–brain barrier (BBB) biomarkers and longitudinal cognitive outcomes were evaluated. Multivariable linear mixed effect models were used to assess the effect of baseline analytes with longitudinal changes in Mini-Mental State Exam (MMSE), Clinical Dementia Rating–Sum of Boxes (CDR-SB), and Logical Memory delayed recall (LM) score after controlling for well-known covariates.

Results

A total of 156 participants included 98 women, 63%; mean age was 74.9 (SD 7.3) years. At baseline, MCI and dementia groups did not differ significantly in TG/HDL-C (Wilcoxon W statistic = 0.39, p = 0.39) and CSF ApoA1 levels (W = 3642, p = 0.29), but the dementia group had higher plasma ApoA1 than the MCI group (W = 4615, p = 0.01). Higher TG/HDL-C ratio was associated with faster decline in CDR-SB among MCI and dementia groups. Higher plasma ApoA1 was associated with faster decline in MMSE and LM among MCI, while in contrast higher CSF ApoA1 levels related to slower cognitive decline in MMSE among MCI. CSF and plasma ApoA1 also show opposite directional correlations with biomarkers of BBB integrity. CSF but not plasma levels of ApoA1 positively correlated to inflammation analytes in the AGE-RAGE signaling pathway in diabetic complications (KEGG ID:KO04933).

Conclusions

Biomarkers of metabolic syndrome relate to rate of cognitive decline among MCI and dementia individuals. Elevated plasma TG/HDL-C ratio and plasma ApoA1 are associated with worse cognitive outcomes in MCI and dementia participants. CSF ApoA1 and plasma ApoA1 likely have different roles in AD progression in MCI stage.
Comparison of OX40 expression in patients with multiple sclerosis and neuromyelitis optica as an approach to diagnosis
Authors: Manian Mostafa , Motallebnezhad Morteza , Nedaeinia Reza , Salehi Rasoul , Khani Leila , Ferns Gordon A. , Jazayeri Mir Hadi
Published: March 2023

Background

Previous studies have shown that CD134 (OX40) co-stimulation is involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) models and the antigen is expressed within multiple sclerosis lesions in humans. OX40 (CD134) is thought to be a secondary co-stimulatory immune checkpoint molecule that is expressed by T cells. This study aimed to evaluate the mRNA expression of OX40 and its serum levels in the peripheral blood of patients with Multiple Sclerosis (MS) or Neuromyelitis Optica (NMO).

Methods

Patients with MS (n = 60), NMO (n = 20), and 20 healthy subjects were recruited from Sina Hospital, Tehran, Iran. The diagnoses were confirmed by a specialist in clinical neurology. Peripheral venous blood was obtained from all subjects, and mRNA quantification of OX40 was conducted using real-time PCR. Serum samples were also obtained and the concentration of OX40 was determined using an enzyme-linked immunosorbent assay (ELISA).

Results

There was a significant correlation between the mRNA expression and serum levels of OX40 and disability as assessed using the expanded disability status scale (EDSS) in the patients with MS, but not in the patients with NMO. Expression of OX40 mRNA was significantly higher in the peripheral blood of MS patients compared to healthy individuals and NMO patients (*P < 0.05). In addition, serum OX40 concentrations were also significantly higher in patients with MS patients compared with healthy subjects (9.08 ± 2.48 vs. 1.49 ± 0.54 ng/ml; P = 0.041).

Conclusions

It appears that an increased expression of OX40 may be associated with the hyperactivation of T cells in patients with MS, and this may play a role in the pathogenesis of the disease.
B cells and T cells abnormalities in patients with selective IgA deficiency
Authors: Bagheri Yasser , Moeini Shad Tannaz , Namazi Shideh , Tofighi Zavareh Farzaneh , Azizi Gholamreza , Salami Fereshteh , Sadani Somayeh , Hosseini Ali , Saeidi Mohsen , Pashangzadeh Salar , Delavari Samaneh , Mirminachi Babak , Rezaei Nima , Abolhassani Hassan , Aghamohammadi Asghar , Yazdani Reza
Published: March 2023

Background

Selective IgA deficiency (SIgAD) is the most prevalent inborn errors of immunity with almost unknown etiology. This study aimed to investigate the clinical diagnostic and prognostic values of lymphocyte subsets and function in symptomatic SIgAD patients.

Methods

A total of 30 available SIgAD patients from the Iranian registry and 30 age-sex-matched healthy controls were included in the present study. We analyzed B and T cell peripheral subsets and T cell proliferation assay by flow cytometry in SIgAD patients with mild and severe clinical phenotypes.

Results

Our results indicated a significant increase in naïve and transitional B cells and a strong decrease in marginal zone-like and switched memory B-cells in SIgAD patients. We found that naïve and central memory CD4+T cell subsets, as well as Th1, Th2 and regulatory T cells, have significantly decreased. On the other hand, there was a significant reduction in central and effector memory CD8+T cell subsets, whereas proportions of both (CD4+and CD8+) terminally differentiated effector memory T cells (TEMRA) were significantly elevated in our patients. Although some T cell subsets in severe SIgAD were similar, a decrease in marginal-zone and switched memory B cells and an increase in CD21lowB cell of severe SIgAD patients were slightly prominent. Moreover, the proliferation activity of CD4+T cells was strongly impaired in SIgAD patients with a severe phenotype.

Conclusion

SIgAD patients have varied cellular and humoral deficiencies. Therefore, T cell and B cell assessment might help in better understanding the heterogeneous pathogenesis and prognosis estimation of the disease.
Long-term efficacy of HDM-SCIT in pediatric and adult patients with allergic rhinitis
Authors: Ren Lei , Wang Chengshuo , Xi Lin , Gao Yunbo , Zhang Yuan , Zhang Luo
Published: March 2023

Background

Subcutaneous immunotherapy (SCIT) is a well-validated and effective disease modification treatment for house dust mites (HDM)-induced allergic rhinitis (AR). Long-term post-treatment comparisons in children and adults treated with SCIT have rarely been published. This study aimed to evaluate the long-term efficacy of HDM-SCIT administered under a cluster schedule in children compared to adults.

Methods

This was an open-design, observational, long-term clinical follow-up study on children and adults with perennial AR treated with HDM-SCIT. The follow-up consisted of a three-year treatment duration plus a post-treatment follow-up of over three years.

Results

Patients in the pediatric (n = 58) and adult (n = 103) groups completed a post-SCIT follow-up of over three years. The total nasal symptom score (TNSS), combined symptom medication score (CSMS), and rhinoconjunctivitis quality-of-life questionnaire (RQLQ) score decreased significantly at T1 (three-year SCIT completed) and T2 (follow-up completed) in the pediatric and adult groups. In both groups, the improvement rate of TNSS (T0-T1) was moderately correlated with the baseline TNSS (r = 0.681, p < 0.001 and r = 0.477, p < 0.001 for children and adults, respectively). Only in the pediatric group, TNSS was significantly lower at T2 compared with that right after SCIT cessation (T1) (p = 0.030).

Conclusions

Children and adults with HDM-induced perennial AR could achieve a sustainable post-treatment efficacy for over three years (up to 13 years) following a three-year SCIT. Patients with relatively severe nasal symptoms at baseline may benefit more from SCIT. Children who have completed an adequate course of SCIT may gain further improvement in nasal symptoms after SCIT cessation.
New transperineal ultrasound-guided biopsy for men in whom PSA is increasing after Miles’ operation
Authors: Park Byung Kwan , Chung Jae Hoon , Song Wan , Kang Minyong , Sung Hyun Hwan , Jeon Hwang Gyun , Jeong Byong Chang , Seo Seong Il , Jeon Seong Soo , Lee Hyun Moo , Kwon Ghee Young
Published: March 2023

Objectives

Currently, a prostate biopsy is guided by transrectal ultrasound (US) alone. However, this biopsy cannot be performed in men without an anus. The aim of this study was to show the outcomes of a new transperineal US (TPUS)-guided biopsy technique in patients who underwent Miles’ operation.

Methods

Between April 2009 and March 2022, TPUS-guided biopsy was consecutively conducted in 9 patients (median, 71 years; range, 61–78 years) with high prostate-specific antigen values (22.60 ng/mL; 6.19–69.7 ng/mL). Their anuses were all removed due to rectal cancer. TPUS-guided biopsy was performed according to information on prostate magnetic resonance imaging. The technical success rate, cancer detection rate, and complication rate were recorded. Tumor sizes were compared between benign and cancer groups using an unpaired t-test with Welch’s correction.

Results

The new TPUS-guided biopsy was successfully performed in all patients. Cancer was detected in 77.8% (7/9) of the patients. These were all categorized as PI-RADS 5. Among them, the detection rate of significant cancer (Gleason score 7 or higher) was 66.7% (6/9). The median tumor size was 2.4 cm (1.7–3.1 cm). However, two patients were diagnosed with benign tissue with PI-RADS 3 or PI-RADS 4. Their median tumor size was 1.0 cm (0.8–1.2 cm). There was significant difference between the cancer and benign groups (p = 0.037) in terms of tumor size. Neither post-biopsy bleeding nor infections occurred.

Conclusions

New TPUS-guided biopsy technique may contribute to detecting large PI-RADS 5 prostate cancer in men after Miles’ operation.
Does deep learning software improve the consistency and performance of radiologists with various levels of experience in assessing bi-parametric prostate MRI?
Authors: Arslan Aydan , Alis Deniz , Erdemli Servet , Seker Mustafa Ege , Zeybel Gokberk , Sirolu Sabri , Kurtcan Serpil , Karaarslan Ercan
Published: March 2023

Objective

To investigate whether commercially available deep learning (DL) software improves the Prostate Imaging-Reporting and Data System (PI-RADS) scoring consistency on bi-parametric MRI among radiologists with various levels of experience; to assess whether the DL software improves the performance of the radiologists in identifying clinically significant prostate cancer (csPCa).

Methods

We retrospectively enrolled consecutive men who underwent bi-parametric prostate MRI at a 3 T scanner due to suspicion of PCa. Four radiologists with 2, 3, 5, and > 20 years of experience evaluated the bi-parametric prostate MRI scans with and without the DL software. Whole-mount pathology or MRI/ultrasound fusion-guided biopsy was the reference. The area under the receiver operating curve (AUROC) was calculated for each radiologist with and without the DL software and compared using De Long’s test. In addition, the inter-rater agreement was investigated using kappa statistics.

Results

In all, 153 men with a mean age of 63.59 ± 7.56 years (range 53–80) were enrolled in the study. In the study sample, 45 men (29.80%) had clinically significant PCa. During the reading with the DL software, the radiologists changed their initial scores in 1/153 (0.65%), 2/153 (1.3%), 0/153 (0%), and 3/153 (1.9%) of the patients, yielding no significant increase in the AUROC (p > 0.05). Fleiss’ kappa scores among the radiologists were 0.39 and 0.40 with and without the DL software (p = 0.56).

Conclusions

The commercially available DL software does not increase the consistency of the bi-parametric PI-RADS scoring or csPCa detection performance of radiologists with varying levels of experience.
Macroprolactinoma with secondary resistance to dopamine agonists: a case report and review of the literature
Authors: Tng Eng-Loon , Teo Ada Ee Der , Aung Aye Thida
Published: March 2023

Background

Resistance to dopamine agonists is not uncommonly seen in prolactinomas. However, development of resistance to dopamine agonists after an initial period of robust treatment response is rare, and only 39 cases have been reported in the past four decades. We describe a Chinese man with this rare condition and explored the postulated mechanisms that may explain this phenomenon. We compiled similar cases that were previously reported and compared their etiology, progress, and response to treatment. On the basis of these cases, we derived a list of differential diagnoses to consider in patients with secondary resistance to dopamine agonists.

Case presentation

A 63-year-old Chinese man presented with blurred vision and was subsequently diagnosed with a macroprolactinoma. He had initial response to cabergoline but developed secondary resistance to it after 5 years. The prolactinoma continued to grow, and his serum prolactin remained markedly elevated despite adherence to escalating dosages of cabergoline up to 6 mg/week. The patient finally underwent transsphenoidal surgery and was found to have a sparsely granulated lactotroph tumor with Ki-67 index of 5%. Postoperatively, there was improvement in his serum prolactin level, although he still required treatment with cabergoline at 6 mg/week.

Conclusions

Surgery can facilitate disease control in patients with prolactinomas that develop secondary resistance to dopamine agonists. Malignant prolactinoma is an important differential diagnosis in this group of patients, especially when serum prolactin remains markedly elevated despite resolution or stability of the primary pituitary lesion, suggesting a metastatic source of prolactin secretion.
Polycythemia with elevated erythropoietin production in a patient with a urinary stone and unilateral hydronephrosis: a case report
Authors: Hajika Yuriko , Kawaguchi Yuji , Hamazaki Kenji , Kumeda Yasuro
Published: March 2023

Background

Absolute polycythemia can be primary or secondary. Erythropoietin-producing diseases (for example, hypoxia) are the major cause of secondary polycythemia. There are reports of polycythemia secondary to hydronephrosis. However, to our knowledge, there is no report on polycythemia secondary to hydronephrosis due to a urinary stone. Herein, we present a case of polycythemia with an elevated erythropoietin level in a patient with a urinary stone and unilateral hydronephrosis.

Case presentation

A 57-year-old Japanese man presented with polycythemia and an elevated erythropoietin level. Erythropoietin accumulation was not due to erythropoietin secretion by a tumor as no obvious lesions were detected on contrast-enhanced computed tomography. Abdominal ultrasonography revealed a stone in the left urinary tract and renal hydronephrosis, and 2 weeks later, the patient underwent transurethral ureterolithotripsy without complications. Blood tests 2 weeks after transurethral ureterolithotripsy showed that the erythropoietin level had declined. Hemoglobin concentration decreased from 20.8 mg/dL before and immediately after transurethral ureterolithotripsy to 15.8 mg/dL 3 months after transurethral ureterolithotripsy. This case was diagnosed as erythropoietin elevation due to unilateral hydronephrosis with a urinary stone, resulting in polycythemia.

Conclusions

Hydronephrosis is a common disease but is not often associated with polycythemia. Further studies are required to elucidate the mechanism and implications of elevated erythropoietin production in hydronephrosis.
BM-MSCs overexpressing the Numb enhance the therapeutic effect on cholestatic liver fibrosis by inhibiting the ductular reaction
Authors: Xu Yan-nan , Xu Wen , Zhang Xu , Wang Dan-yang , Zheng Xin-rui , Liu Wei , Chen Jia-mei , Chen Gao-feng , Liu Cheng-hai , Liu Ping , Mu Yong-ping
Published: March 2023

Background

Cholestatic liver fibrosis (CLF) is caused by inflammatory destruction of the intrahepatic bile duct and abnormal proliferation of the small bile duct after cholestasis. Activation of the Notch signaling pathway is required for hepatic stem cells to differentiate into cholangiocytes during the pathogenesis of CLF. Our previous research found that the expression of the Numb protein, a negative regulator of Notch signaling, was significantly reduced in the livers of patients with primary biliary cholangitis and CLF rats. However, the relationship between the Numb gene and CLF is largely unclear. In this study, we investigated the role of the Numb gene in the treatment of bile duct ligation (BDL)-induced CLF.

Methods

In vivo, bone marrow-derived mesenchymal stem cells (BM-MSCs) with Numb gene overexpression or knockdown obtained using lentivirus transfection were transplanted into the livers of rats with BDL-induced CLF. The effects of the Numb gene on stem cell differentiation and CLF were evaluated by performing histology, tests of liver function, and measurements of liver hydroxyproline, cytokine gene and protein levels. In vitro, the Numb gene was overexpressed or knocked down in the WB-F344 cell line by lentivirus transfection, Then, cells were subjected immunofluorescence staining and the detection of mRNA levels of related factors, which provided further evidence supporting the results from in vivo experiments.

Results

BM-MSCs overexpressing the Numb gene differentiated into hepatocytes, thereby inhibiting CLF progression. Conversely, BM-MSCs with Numb knockdown differentiated into biliary epithelial cells (BECs), thereby promoting the ductular reaction (DR) and the progression of CLF. In addition, we confirmed that knockdown of Numb in sodium butyrate-treated WB-F344 cells aggravated WB-F344 cell differentiation into BECs, while overexpression of Numb inhibited this process.

Conclusions

The transplantation of BM-MSCs overexpressing Numb may be a useful new treatment strategy for CLF.
Semi-quantitative indices of 2-[18F]FDG PET/CT in assessing cardiovascular and non-cardiovascular manifestations of IgG4-related disease and treatment response
Authors: Chen Mingwei , Tang Charlene Yu Lin , Fong Warren Weng Seng , Lam Winnie Wing-Chuen
Published: March 2023

Background

IgG4-related disease (IgG4-RD) is a heterogeneous autoimmune disorder characterised by inflammatory lesions. Diagnostic imaging, such as 2-[18F]FDG PET/CT, is critical in evaluation of the disease, especially for potentially lethal cardiovascular manifestations. This retrospective study examines the usefulness of semi-quantitative parameters of 2-[18F]FDG PET/CT in monitoring IgG4-RD in patients with and without cardiovascular manifestations.

Methods

Patients diagnosed with IgG4-RD who underwent a 2-[18F]FDG PET/CT scan were identified and classified based on presence or absence of cardiovascular disease. Clinical and laboratory data were extracted and compared to three 2-[18F]FDG PET/CT semi-quantitative parameters: maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG). Tissue-to-background blood (TBR) values were also evaluated for cardiovascular manifestations. These data were also compared in patients before and after receiving immunosuppressive therapy.

Results

Forty-six patients identified were divided into an eight member subgroup of patients with cardiovascular manifestations, and a thirty-eight member subgroup of patients without. Patients with cardiovascular lesions were most frequently identified incidentally on imaging evaluation for other diseases (37.5%), with none presenting with chest pain or other cardiovascular symptoms. Ten patients with pre-treatment and post-treatment 2-[18F]FDG PET/CT scans demonstrated significant decreases in all semi-quantitative parameters, with no significant decrease in total IgG or ESR. The decrease in SUVmax, MTV, TLG following therapy was replicated in patients with and without cardiovascular manifestations.

Conclusion

2-[18F]FDG PET/CT is an important investigation to determine all sites of involvement in this multisystemic disease and to rule out life-threatening cardiovascular manifestations even in the absence of symptoms. Semi-quantitative parameters such as SUVmax, MTV, TLG, and TBR are useful in assessing treatment response in patients. There are no serological substitutes that can quantify the extent of disease involvement like 2-[18F]FDG PET/CT.
Economic evaluation of strategies against coronavirus: a systematic review
Authors: Izadi Reyhane , Hatam Nahid , Baberi Fatemeh , Yousefzadeh Setareh , Jafari Abdosaleh
Published: March 2023

Background

The COVID-19 outbreak was defined as a pandemic on 11 March 2020 by the World Health Organization. After that, COVID-19 has enormously influenced health systems around the world, and it has claimed more than 4.2 million deaths until July 2021. The pandemic has led to global health, social and economic costs. This situation has prompted a crucial search for beneficial interventions and treatments, but little is known about their monetary value. This study is aimed at systematically reviewing the articles conducted on the economic evaluation of preventive, control and treatment strategies against COVID-19.

Material and method

We searched PubMed, Web of Science, Scopus, and Google Scholar from December 2019 to October 2021 to find applicable literature to the economic evaluation of strategies against COVID-19. Two researchers screened potentially eligible titles and abstracts. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was used to quality assessment of studies.

Results

Thirty-six studies were included in this review, and the average CHEERS score was 72. Cost-effectiveness analysis was the most common type of economic evaluation, used in 21 studies. And the quality-adjusted life year (QALY) was the main outcome applied to measure the effectiveness of interventions, which was used in 19 studies. In addition, articles were reported a wide range of incremental cost-effectiveness ratio (ICER), and the lowest cost per QALY ($321.14) was related to the use of vaccines.

Conclusion

Based on the results of this systematic review, it seems that all strategies are likely to be more cost-effective against COVID-19 than no intervention and vaccination was the most cost-effective strategy. This research provides insight for decision makers in choosing optimal interventions against the next waves of the current pandemic and possible future pandemics.
Novel adjuvant nano-vaccine induced immune response against Acinetobacter baumannii
Authors: Piri-Gharaghie Tohid , Doosti Abbas , Mirzaei Seyed Abbas
Published: March 2023

Developing adjuvant vaccines to combat rising multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections is a promising and cost-effective approach. The aim of this analysis was to construct a pDNA-CPG C274-adjuvant nano-vaccine and investigate its immunogenicity and protection in BALB/c mice. The CPG ODN C274 adjuvant was chemically synthesized and cloned into pcDNA3.1( +), and the cloning was verified using PCR and BamHI/EcoRV restriction enzyme digestion. Then, utilizing a complex coacervation approach, pDNA-CPG C274 was encapsulated by chitosan (CS) nanoparticles (NPs). TEM and DLS are used to explore the properties of the pDNA/CSNP complex. TLR-9 pathway activation was investigated in human HEK-293 and RAW 264.7 mouse cells. The vaccine's immunogenicity and immune-protective effectiveness were investigated in BALB/c mice. The pDNA-CPG C274/CSNPs were small (mean size 79.21 ± 0.23 nm), positively charged (+ 38.87 mV), and appeared to be spherical. A continuous slow release pattern was achieved. TLR-9 activation was greatest in the mouse model with CpG ODN (C274) at concentrations of 5 and 10 μg/ml with 56% and 55%, respectively (**P < 0.01). However, in HEK-293 human cells, by increasing the concentration of CpG ODN (C274) from 1 to 50 μg/ml, the activation rate of TLR-9 also increased, so that the highest activation rate (81%) was obtained at the concentration of 50 μg/ml (***P < 0.001). pDNA-CPG C274/CSNPs immunized BALB/c mice produced increased amounts of total-IgG, as well as IFN-γ and IL-1B in serum samples, compared to non-encapsulated pDNA-CPG C274. Furthermore, liver and lung injuries, as well as bacterial loads in the liver, lung, and blood, were reduced, and BALB/c mice immunized with pDNA-CPG C274/CSNPs showed potent protection (50–75%) against acute fatal Intraperitoneal A. baumannii challenge. pDNA-CPG C274/CSNPs evoked total-IgG antibodies, Th1 cellular immunity, and the TLR-9 pathway, as well as protection against an acute fatal A. baumannii challenge. Our findings suggest that this nano-vaccine is a promising approach for avoiding A. baumannii infection when used as a powerful adjuvant.
A fabricated hydrogel of hyaluronic acid/curcumin shows super-activity to heal the bacterial infected wound
Authors: Khaleghi Maryam , Haghi Fakhri , Gholami Mina , Hourfar Hamdam , Shahi Farshad , Mir Mousavi Zekoloujeh Ali , Aliakbari Farhang , Ahmadi Ebrahim , Morshedi Dina
Published: March 2023

High risk of acute morbidities and even mortality from expanding the antibiotics resistant infectious wounds force indefinite efforts for development of high performance wound-healing materials. Herein, we design a procedure to fabricate a hyaluronic acid (HA)-based hydrogel to conjugate curcumin (Gel-H.P.Cur). The highlight of this work is to provide a favorite condition for capturing curcumin while protecting its structure and intensifying its activities because of the synchronization with HA. Accordingly, HA as a major component of dermis with a critical role in establishing skin health, could fortify the wound healing property as well as antibacterial activity of the hydrogel. Gel-H.P.Cur showed antibacterial properties against Pseudomonas aeruginosa (P. aeruginosa), which were examined by bactericidal efficiency, disk diffusion, anti-biofilm, and pyocyanin production assays. The effects of Gel-H.P.Cur on the inhibition of quorum sensing (QS) regulatory genes that contribute to expanding bacteria in the injured place was also significant. In addition, Gel-H.P.Cur showed high potential to heal the cutaneous wounds on the mouse excisional wound model with repairing histopathological damages rapidly and without scar. Taken together, the results strongly support Gel-H.P.Cur as a multipotent biomaterial for medical applications regarding the treatment of chronic, infected, and dehiscent wounds.
Identification of the feed supplements commonly utilised by communal beef cattle farmers during the dry season at Ga-Matlala, Limpopo province
Authors: Monkwe T. R. , Gxasheka M. , Gunya B.
Published: March 2023

A survey was carried out to identify the feed supplements commonly utilised by communal beef cattle farmers and investigate knowledge and perception of farmers on the feed supplement during the dry season in Ga-Matlala, whether they assess the feed supplements before feeding to cattle and their perception on how they affect cattle. A structured questionnaire was used to collect data from a total of 59 cattle farmers from three rural villages (Phofu, Phetole and Madietane) in the Ga-Matlala area using a snowball sampling technique. In the studied area, males outnumbered females, with the majority aged 55 and older. The majority of respondents were cattle owners with 16 years or more of farming experience. Secondary school was the most frequently reported educational background, followed by primary school whereas 20.3% of respondents never attended school. The most common cattle breed owned was Nguni, while Afrikaner was the second most common breed. More than 50% of respondents reported releasing cattle in the morning and returning late to provide them with feed supplements and water. The majority of respondents were using feed supplements during the dry season, and the most feed supplements that were identified in the study areas are lucerne hay and maize stover. Lucerne hay and maize stover were the most commonly used and acceptable supplementary feeds during the dry season. The major reasons for feeding cattle with lucerne hay and maize stover were reported to be weight gain and average weight gain of cattle, respectively. The majority of farmers reported that they do not assess the quality of supplementary feeds especially those who supplement with lucerne hay. However, the remaining percentage of farmers assesses the quality of lucerne hay by checking the moisture content and moulds in the feed supplements. It is thus concluded that there is a need for more knowledge and information on the overall quality of the locally available dry season supplementary feeds for enhancing productivity in communal areas.
SEPT2 crotonylation promotes metastasis and recurrence in hepatocellular carcinoma and is associated with poor survival
Authors: Zhang Xin-yue , Liu Ze-xian , Zhang Yi-fan , Xu Li-xia , Chen Meng-ke , Zhou Yu-feng , Yu Jun , Li Xiao-xing , Zhang Ning
Published: March 2023

Background

Hepatocellular carcinoma (HCC) metastasis and recurrence lead to therapy failure, which are closely associated with the proteome. However, the role of post-translational modification (PTM) in HCC, especially for the recently discovered lysine crotonylation (Kcr), is elusive.

Results

We investigated the correlation between crotonylation and HCC in 100 tumor tissues and performed stable isotope labeling by amino acids and liquid chromatography tandem mass spectrometry in HCC cells, and we found that crotonylation was positively correlated with HCC metastasis, and higher crotonylation in HCC cells facilitated cell invasiveness. Through bioinformatic analysis, we found that the crotonylated protein SEPT2 was significantly hypercrotonylated in highly invasive cells, while the decrotonylated mutation of SEPT2-K74 impaired SEPT2 GTPase activity and inhibited HCC metastasis in vitro and in vivo. Mechanistically, SIRT2 decrotonylated SEPT2, and P85α was found to be the downstream effector of SEPT2. Moreover, we identified that SEPT2-K74cr was correlated with poor prognosis and recurrence in HCC patients, thus indicating its clinical potential as an independent prognostic factor.

Conclusions

We revealed the role of nonhistone protein crotonylation in regulating HCC metastasis and invasion. Crotonylation facilitated cell invasion through the crotonylated SEPT2-K74-P85α-AKT pathway. High SEPT2-K74 crotonylation predicted poor prognosis and a high recurrence rate in HCC patients. Our study revealed a novel role of crotonylation in promoting HCC metastasis.
ISL1 controls pancreatic alpha cell fate and beta cell maturation
Authors: Bohuslavova Romana , Fabriciova Valeria , Lebrón-Mora Laura , Malfatti Jessica , Smolik Ondrej , Valihrach Lukas , Benesova Sarka , Zucha Daniel , Berkova Zuzana , Saudek Frantisek , Evans Sylvia M , Pavlinkova Gabriela
Published: March 2023

Background

Glucose homeostasis is dependent on functional pancreatic α and ß cells. The mechanisms underlying the generation and maturation of these endocrine cells remain unclear.

Results

We unravel the molecular mode of action of ISL1 in controlling α cell fate and the formation of functional ß cells in the pancreas. By combining transgenic mouse models, transcriptomic and epigenomic profiling, we uncover that elimination of Isl1 results in a diabetic phenotype with a complete loss of α cells, disrupted pancreatic islet architecture, downregulation of key ß-cell regulators and maturation markers of ß cells, and an enrichment in an intermediate endocrine progenitor transcriptomic profile.

Conclusions

Mechanistically, apart from the altered transcriptome of pancreatic endocrine cells, Isl1 elimination results in altered silencing H3K27me3 histone modifications in the promoter regions of genes that are essential for endocrine cell differentiation. Our results thus show that ISL1 transcriptionally and epigenetically controls α cell fate competence, and ß cell maturation, suggesting that ISL1 is a critical component for generating functional α and ß cells.
Loss of TTC17 promotes breast cancer metastasis through RAP1/CDC42 signaling and sensitizes it to rapamycin and paclitaxel
Authors: Zhang Jingyao , Guo Fengzhu , Li Chunxiao , Wang Yang , Wang Jinsong , Sun Fangzhou , Zhou Yantong , Ma Fei , Zhang Bailin , Qian Haili
Published: March 2023

Background

Breast cancer (BC) metastasis is the leading cause of poor prognosis and therapeutic failure. However, the mechanisms underlying cancer metastasis are far from clear.

Methods

We screened candidate genes related to metastasis through genome-wide CRISPR screening and high-throughput sequencing of patients with metastatic BC, followed by a panel of metastatic model assays. The effects of tetratricopeptide repeat domain 17 (TTC17) on migration, invasion, and colony formation ability together with the responses to anticancer drugs were investigated in vitro and in vivo. The mechanism mediated by TTC17 was determined by RNA sequencing, Western blotting, immunohistochemistry, and immunofluorescence. The clinical significance of TTC17 was evaluated using BC tissue samples combined with clinicopathological data.

Results

We identified the loss of TTC17 as a metastasis driver in BC, and its expression was negatively correlated with malignancy and positively correlated with patient prognosis. TTC17 loss in BC cells promoted their migration, invasion, and colony formation capacity in vitro and lung metastasis in vivo. Conversely, overexpressing TTC17 suppressed these aggressive phenotypes. Mechanistically, TTC17 knockdown in BC cells resulted in the activation of the RAP1/CDC42 pathway along with a disordered cytoskeleton in BC cells, and pharmacological blockade of CDC42 abolished the potentiation of motility and invasiveness caused by TTC17 silencing. Research on BC specimens demonstrated reduced TTC17 and increased CDC42 in metastatic tumors and lymph nodes, and low TTC17 expression was linked to more aggressive clinicopathologic characteristics. Through screening the anticancer drug library, the CDC42 inhibitor rapamycin and the microtubule-stabilizing drug paclitaxel showed stronger inhibition of TTC17-silenced BC cells, which was confirmed by more favorable efficacy in BC patients and tumor-bearing mice receiving rapamycin or paclitaxel in the TTC17Low arm.

Conclusions

TTC17 loss is a novel factor promoting BC metastasis, that enhances migration and invasion by activating RAP1/CDC42 signaling and sensitizes BC to rapamycin and paclitaxel, which may improve stratified treatment strategies under the concept of molecular phenotyping-based precision therapy of BC.
Stem cell therapy combined with controlled release of growth factors for the treatment of sphincter dysfunction
Authors: Shan Shengzhou , Li Qingfeng , Criswell Tracy , Atala Anthony , Zhang Yuanyuan
Published: March 2023

Sphincter dysfunction often occurs at the end of tubule organs such as the urethra, anus, or gastroesophageal sphincters. It is the primary consequence of neuromuscular impairment caused by trauma, inflammation, and aging. Despite intensive efforts to recover sphincter function, pharmacological treatments have not achieved significant improvement. Cell- or growth factor-based therapy is a promising approach for neuromuscular regeneration and the recovery of sphincter function. However, a decrease in cell retention and viability, or the short half-life and rapid degradation of growth factors after implantation, remain obstacles to the translation of these therapies to the clinic. Natural biomaterials provide unique tools for controlled growth factor delivery, which leads to better outcomes for sphincter function recovery in vivo when stem cells and growth factors are co-administrated, in comparison to the delivery of single therapies. In this review, we discuss the role of stem cells combined with the controlled release of growth factors, the methods used for delivery, their potential therapeutic role in neuromuscular repair, and the outcomes of preclinical studies using combination therapy, with the hope of providing new therapeutic strategies to treat incontinence or sphincter dysfunction of the urethra, anus, or gastroesophageal tissues, respectively.
Clinical significance of human metapneumovirus detection in critically ill adults with lower respiratory tract infections
Authors: Kapandji Natacha , Darmon Michael , Valade Sandrine , Salmona Maud , Legoff Jérôme , Zafrani Lara , Azoulay Elie , Lemiale Virginie
Published: March 2023

Background

Unlike other viruses, the pathogenicity of human metapneumovirus (hMPV) in adults remains uncertain. To address this question, a retrospective monocentric cohort including all patients admitted to ICU with hMPV infection between January 1, 2010, and June 30, 2018 was performed. The characteristics of hMPV infected patients were studied and compared to matched influenza infected patients. Consecutively, a systematic review and meta-analyses investigating PUBMED, EMBASE and COCHRANE databases was conducted to explore the hMPV infections in adult patients (PROSPERO number: CRD42018106617). Trials, case series, and cohorts published between January 1, 2008 and August 31, 2019 compiling adults presenting hMPV infections were included. Pediatric studies were excluded. Data were extracted from published reports. Primary endpoint was the rate of low respiratory tract infections (LRTIs) among all hMPV infected patients.

Results

During the study period, 402 patients were tested positive for hMPV. Among them 26 (6.5%) patients were admitted to the ICU, 19 (4.7%) for acute respiratory failure. Twenty-four (92%) were immunocompromised. Bacterial coinfections were frequent 53.8%. Hospital mortality rate was 30.8%. In the case–control analysis, the clinical and imaging characteristics were not different between hMPV and influenza infected patients. The systematic review identified 156 studies and 69 of them (1849 patients) were eligible for analysis. Although there was heterogeneity between the studies, the rate of hMPV LRTIs was 45% (95% CI 31–60%; I2 = 98%). Intensive care unit (ICU) admission was required for 33% (95% CI 21–45%; I2 = 99%). Hospital mortality rate was 10% (95% CI 7–13%; I2 = 83%) and ICU mortality rate was 23% (95% CI 12–34%; I2 = 65%). Underlying malignancy was independently associated with increased mortality rate.

Conclusions

This preliminary work suggested that hMPV may be associated with severe infection and high mortality in patients with underlying malignancies. However, regarding the small size of the cohort and the heterogeneity of the review, more cohort studies are warranted.
Optimal deployment of large-scale wireless sensor networks based on graph clustering and matrix factorization
Authors: Gao Hefei , Zhu Qianwen , Wang Wei
Published: March 2023

It is undeniable that there are a large number of redundant nodes in a wireless sensor network. These redundant nodes cause a colossal waste of resources and seriously threaten the life of the sensor network. In this paper, we provide a sensor nodes optimization selection algorithm based on a graph for a large-scale wireless sensor network. Firstly, we propose a representation-clustering joint algorithm based on Graph Neural Network to partition the large-scale graph into several subgraphs. Then, we use Singular-Value-QR Decomposition for the node selection of each subgraph and achieve the optimal deployment for a large-scale wireless sensor network. We conduct the experiments on the CIMIS dataset. The results show that the mean square error between the reconstructed network and the original network is as low as 0.02433. Meanwhile, we also compare our algorithm with the classical optimization algorithm. The results imply that the mean square error of the proposed algorithm is lower and the distribution is more uniform. Further, we verify the scalability of the algorithm for the optimal deployment of the large-scale wireless sensor network.
Learning spatial regularized correlation filters with response consistency and distractor repression for UAV tracking
Authors: Zhang Wei
Published: March 2023

Correlation filter-based trackers have made significant progress in visual object tracking for various types of unmanned aerial vehicle (UAV) applications due to their promising performance and efficiency. However, the boundary effect remains a challenging problem. Several methods enlarge search areas to handle this shortcoming but introduce more background noise, and the filter is prone to learn from distractors. To address this issue, we present spatial regularized correlation filters with response consistency and distractor repression. Specifically, a temporal constraint is introduced to reinforce the consistency across frames by minimizing the difference between consecutive correlation response maps. A dynamic spatial constraint is also integrated by exploiting the local maximum points of the correlation response produced during the detection phase to mitigate the interference from background distractions. The proposed appearance model can optimize the temporal and spatial constraints together with a spatial regularization weight simultaneously. Meanwhile, the proposed appearance model can be solved effectively based on the alternating direction method of multipliers algorithm. The spatial and temporal information concealed in the response maps is fully taken into consideration to boost overall tracking performance. Extensive experiments are conducted on a public UAV benchmark dataset with 123 challenging sequences. The experimental results and analysis demonstrate that the proposed method outperforms 12 state-of-the-art trackers in terms of both accuracy and robustness while efficiently operating in real time.
Decision-level fusion detection method of visible and infrared images under low light conditions
Authors: Hu Zuhui , Jing Yaguang , Wu Guoqing
Published: March 2023

Aiming at the problem of poor effect of object detection with visible images under low light conditions, the decision-level fusion detection method of visible and infrared images is studied. Taking YOLOX as the object detection network based on deep learning, a decision-level fusion detection algorithm of visible and infrared images based on light sensing is proposed. Experiments are carried out on LLVIP dataset, which is a visible-infrared paired dataset for low light vision. Through comparative analysis, it is found that the decision-level fusion algorithm based on Soft-NMS and light sensing obtained the optimal AP value of 69.0%, which is 11.4% higher than the object detection with visible images and 1.1% higher than the object detection with infrared images. The experimental results show that the decision-level fusion algorithm based on Soft-NMS and light sensing can effectively fuse the complementary information of visible and infrared images, and improve the object detection effect under low light conditions.