bluuebunny/crossref_metadata_2025 huggingface dataset:
Naïve CD4+ cell counts significantly decay and high HIV RNA levels contribute to immunological progression in long-term non-progressors infected with HIV by blood products: a cohort study
Authors: Xu Ling , Liu Yubin , Song Xiaojing , Li Yanling , Han Yang , Zhu Ting , Cao Wei , Li Taisheng
Published: June 2021

Background

Some long-term non-progressors (LTNPs) have decreasing CD4+ T cell counts and progress to AIDS. Exploring which subsets of CD4+ T cell decreasing and the determinants associated with the decay in these patients will improve disease progression surveillance and provide further understanding of HIV pathogenesis.

Methods

Twenty-five LTNPs infected with HIV by blood products were classified as decreased (DG) if their CD4+ cell count dropped to < 400 cells/μL during follow-up or as non-decreased (non-DG) if their CD4+ cell count was ≥400 cells/μL. Laboratory and clinical assessments were conducted at 6 consecutive visits to identify DG characteristics.

Results

The LTNPs were infected with HIV for 12 (IQR: 11.5–14) years, and 23 were classified as the B′ subtype. Six individuals lost LTNP status 14.5 (IQR: 12.5–17.5) years after infection (DG), and the CD4+ T cell count decreased to 237 (IQR: 213–320) cells/μL at the latest visit. The naïve CD4+ T cell count decrease was greater than that of memory CD4+ T cells [− 128 (IQR: − 196, − 107) vs − 64 (IQR: − 182, − 25) cells/μL)]. Nineteen individuals retained LTNP status (non-DG). At enrolment, the viral load (VL) level (p = 0.03) and CD8+CD38+ percentage (p = 0.03) were higher in DG than non-DG individuals. During follow-up, viral load and CD8+CD38+ percentage were significantly increased and negatively associated with CD4+ cell count [(r = − 0.529, p = 0.008), (r = − 0.476, p = 0.019), respectively]. However, the CD8+CD28+ percentage and B cell count dropped in DG and were positively correlated with CD4+ T cell count [(r = 0.448, p = 0.028), (r = 0.785, p < 0.001)].

Conclusion

Immunological progression was mainly characterized by the decrease of naïve CD4+ T cell in LTNPs infected with HIV by blood products and it may be associated with high HIV RNA levels.
Native T1 mapping and extracellular volume fraction for differentiation of myocardial diseases from normal CMR controls in routine clinical practice
Authors: Thongsongsang Rawiwan , Songsangjinda Thammarak , Tanapibunpon Prajak , Krittayaphong Rungroj
Published: June 2021

Background

This study aimed to determine native T1 and extracellular volume fraction (ECV) in distinct types of myocardial disease, including amyloidosis, dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), myocarditis and coronary artery disease (CAD), compared to controls.

Methods

We retrospectively enrolled patients with distinct types of myocardial disease, CAD patients, and control group (no known heart disease and negative CMR study) who underwent 3.0 Tesla CMR with routine T1 mapping. The region of interest (ROI) was drawn in the myocardium of the mid left ventricular (LV) short axis slice and at the interventricular septum of mid LV slice. ECV was calculated by actual hematocrit (Hct) and synthetic Hct. T1 mapping and ECV was compared between myocardial disease and controls, and between CAD and controls. Diagnostic yield and cut-off values were assessed.

Results

A total of 1188 patients were enrolled. The average T1 values in the control group were 1304 ± 42 ms at septum, and 1294 ± 37 ms at mid LV slice. The average T1 values in patients with myocardial disease and CAD were significantly higher than in controls (1441 ± 72, 1349 ± 59, 1345 ± 59, 1355 ± 56, and 1328 ± 54 ms for septum of amyloidosis, DCM, HCM, myocarditis, and CAD). Native T1 of the mid LV level and ECV at septum and mid LV with actual and synthetic Hct of patients with myocardial disease or CAD were significantly higher than in controls.

Conclusions

Although native T1 and ECV of patients with cardiomyopathy and CAD were significantly higher than controls, the values overlapped. The greatest clinical utilization was found for the amyloidosis group.
Impact of pericardial fluid glucose level and computed tomography attenuation values on diagnosis of malignancy-related pericardial effusion
Authors: Nakamura Takashi , Okune Mana , Yasuda Masakazu , Watanabe Heitaro , Ueno Masafumi , Yamaji Kenji , Mizutani Kazuki , Kurita Takashi , Nakazawa Gaku
Published: June 2021

Background

We evaluated malignancy according to the characteristics of pericardial fluid in symptomatic Japanese patients undergoing pericardiocentesis and computed tomography (CT).

Methods

This was a retrospective, single-center, observational study of 125 symptomatic patients undergoing pericardiocentesis. The patients were classified into two groups: a malignancy group and a non-malignancy group, according to the primary disease and cytology of the pericardial effusion (PE). We compared the pericardial fluid sample and CT measurements between both groups.

Results

All patients were diagnosed as having exudative PE by Light’s criteria. PE with malignant cells was demonstrated in 76.8% of the malignancy group patients. Pericardial to serum lactate dehydrogenase (LDH) ratio > 0.6, as one of Light’s criteria, was associated with malignancy (p = 0.017). Lower serum brain natriuretic peptide (BNP) concentration was also associated with malignancy (BNP: 126.9 ± 89.8 pg/ml vs 409.2 ± 97.7 pg/ml, malignancy vs non-malignancy groups, respectively; p = 0.037). A significant difference was observed in pericardial fluid glucose level between the malignancy and non-malignancy groups (pericardial fluid glucose: 78.24 ± 48.29 mg/dl vs 98.41 ± 44.85, respectively; p = 0.048). Moreover, CT attenuation values (Hounsfield units (HU)) tended to be higher in the malignancy group vs the non-malignancy group (22.7 [interquartile range (IQR), 17.4–26.0] vs 17.4 [IQR, 13.7–26.4], respectively; p = 0.08). The sensitivity and specificity of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 40.9% and 89.6%, respectively, in the malignancy group. The positive- and negative predictive values of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 85.7% and 50.0%, respectively, in the malignancy group. Pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were cutoff values associated with malignancy (p = 0.012).

Conclusions

Lower pericardial fluid glucose level with higher CT attenuation values may suggest malignancy-related PE.
A rare case of posterior reversible encephalopathy syndrome in a patient with severe leptospirosis complicated with rhabdomyolysis and acute kidney injury; a case report
Authors: Lakmali Jayawardane Pathiranage Roneesha , Thirumavalavan Kanapathipillei , Dissanayake Danapala
Published: June 2021

Background

Leptospirosis is a zoonotic spirochetal disease caused by Leptospira interrogans. The clinical presentation ranges from an asymptomatic state to a fatal multiorgan dysfunction. Neurological manifestations including aseptic meningitis, spinal cord and peripheral nerve involvement, cranial neuropathies and cerebellar syndrome are well recognized with varying frequencies among patients with this disease. Posterior reversible encephalopathy syndrome is a very rare occurrence in leptospirosis and only two cases are reported in the medical literature up to now. We report a case of posterior reversible encephalopathy syndrome in a patient with leptospirosis with rhabdomyolysis and acute kidney injury.

Case presentation

A 21 year-old male presented with fever and oliguric acute kidney injury with rhabdomyolysis. A diagnosis of leptospirosis was made and he was being managed according to the standard practice together with regular hemodialysis. The clinical condition was improving gradually. On day 8 of the illness, he developed headache and sudden painless complete bilateral vision loss followed by several brief generalized tonic clonic seizure attacks. Examination was significant for a Glasgow Coma Scale of 14/15, blood pressure of 150/90 mmHg and complete bilateral blindness. The findings of magnetic resonance imaging of the brain were compatible with posterior reversible encephalopathy syndrome. He was managed with blood pressure control and antiepileptics with supportive measures and standard treatment for leptospirosis and made a complete recovery.

Conclusion

Posterior reversible encephalopathy syndrome, though very rare with leptospirosis, should be considered as a differential diagnosis in a patient with new onset visual symptoms and seizures, especially during the immune phase. Optimal supportive care together with careful blood pressure control and seizure management would yield a favourable outcome in this reversible entity.
Combined frameless stereotactical biopsy and intraoperative cerebral angiography by 3D-rotational fluoroscopy with intravenous contrast administration: a feasibility study
Authors: Linsenmann Thomas , Cattaneo Andrea , März Alexander , Weiland Judith , Stetter Christian , Nickl Robert , Westermaier Thomas
Published: June 2021

Background

Mobile 3-dimensional fluoroscopes are an integral part of modern neurosurgical operating theatres and can also be used in combination with free available image post processing to depict cerebral vessels. In preparation of stereotactic surgery, preoperative Computed Tomography (CT) may be required for image fusion. Contrast CT may be of further advantage for image fusion as it regards the vessel anatomy in trajectory planning. Time-consuming in-hospital transports are necessary for this purpose. Mobile 3D-fluoroscopes may be used to generate a CT equal preoperative data set without an in-hospital transport. This study was performed to determine the feasibility and image quality of intraoperative 3-dimensional fluoroscopy with intravenous contrast administration in combination with stereotactical procedures.

Methods

6 patients were included in this feasibility study. After fixation in a radiolucent Mayfield clamp a rotational fluoroscopy scan was performed with 50 mL iodine contrast agent. The image data sets were merged with the existing MRI images at a planning station and visually evaluated by two observer. The operation times were compared between the frame-based and frameless systems (“skin-to-skin” and “OR entry to exit”).

Results

The procedure proves to be safe. The entire procedure from fluoroscope positioning to the transfer to the planning station took 5–6 min with an image acquisition time of 24 s. In 5 of 6 cases, the fused imaging was able to reproduce the vascular anatomy accurately and in good quality. Both time end-points were significantly shorter compared to frame-based interventions.

Conclusion

The images could easily be transferred to the planning and navigation system and were successfully merged with the MRI data set. The procedure can be completely integrated into the surgical workflow. Preoperative CT imaging or transport under anaesthesia may even be replaced by this technique in the future. Furthermore, hemorrhages can be successfully visualized intraoperatively and might prevent time delays in emergencies.
Reduced fecal short-chain fatty acids levels and the relationship with gut microbiota in IgA nephropathy
Authors: Chai Lingxiong , Luo Qun , Cai Kedan , Wang Kaiyue , Xu Binbin
Published: June 2021

Background

IgA nephropathy(IgAN)) is the common pathological type of glomerular diseases. The role of gut microbiota in mediating “gut-IgA nephropathy” has not received sufficient attention in the previous studies. The purpose of this study was to investigate the changes of fecal short-chain fatty acids(SCFAs), a metabolite of the intestinal microbiota, in patients with IgAN and its correlation with intestinal flora and clinical indicators, and to further investigate the role of the gut-renal axis in IgAN.

Methods

There were 29 patients with IgAN and 29 normal control subjects recruited from January 2018 to May 2018. The fresh feces were collected. The fecal SCFAs were measured by gas chromatography/mass spectrometry and gut microbiota was analysed by16S rDNA sequences, followed by estimation of α- and β-diversity. Correlation analysis was performed using the spearman’s correlation test between SCFAs and gut microbiota.

Results

The levels of acetic acid, propionic acid, butyric acid, isobutyric acid and caproic acid in the IgAN patients were significantly reduced compared with control group(P < 0.05). Butyric acid(r=-0.336, P = 0.010) and isobutyric acid(r=-0.298, P = 0.022) were negatively correlated with urea acid; butyric acid(r=-0.316, P = 0.016) was negatively correlated with urea nitrogen; caproic acid(r=-0.415,P = 0.025) showed negative correlation with 24-h urine protein level.Exemplified by the results of α-diversity and β-diversity, the intestinal flora of IgAN patients was significantly different from that of the control group. Acetic acid was positively associated with c_Clostridia(r = 0.357, P = 0.008), o_Clostridiales(r = 0.357, P = 0.008) and g_Eubacterium_coprostanoligenes_group(r = 0.283, P = 0.036). Butyric acid was positively associated with g_Alistipes (r = 0.278, P = 0.040). The relative abundance of those were significantly decreased in IgAN group compared to control group.

Conclusions

The levels of fecal SCFAs in the IgAN patients were reduced, and correlated with clinical parameters and gut microbiota, which may be involved in the pathogenesis of IgAN, and this finding may provide a new therapeutic approach.
The lipid-lowering drug fenofibrate combined with si-HOTAIR can effectively inhibit the proliferation of gliomas
Authors: Zhu Wei , Zhao Hongyang , Xu Fenfen , Huang Bin , Dai Xiaojing , Sun Jikui , Nyalali Alphonce M. K. , Zhang Kailiang , Ni Shilei
Published: June 2021

Background

Fenofibrate is a fibric acid derivative known to have a lipid-lowering effect. Although fenofibrate-induced peroxisome proliferator-activated receptor alpha (PPARα) transcription activation has been shown to play an important role in the malignant progression of gliomas, the underlying mechanisms are poorly understood.

Methods

In this study, we analyzed TCGA database and found that there was a significant negative correlation between the long noncoding RNA (lncRNA) HOTAIR and PPARα. Then, we explored the molecular mechanism by which lncRNA HOTAIR regulates PPARα in cell lines in vitro and in a nude mouse glioma model in vivo and explored the effect of the combined application of HOTAIR knockdown and fenofibrate treatment on glioma invasion.

Results

For the first time, it was shown that after knockdown of the expression of HOTAIR in gliomas, the expression of PPARα was significantly upregulated, and the invasion and proliferation ability of gliomas were obviously inhibited. Then, glioma cells were treated with both the PPARα agonist fenofibrate and si-HOTAIR, and the results showed that the proliferation and invasion of glioma cells were significantly inhibited.

Conclusions

Our results suggest that HOTAIR can negatively regulate the expression of PPARα and that the combination of fenofibrate and si-HOTAIR treatment can significantly inhibit the progression of gliomas. This introduces new ideas for the treatment of gliomas.
Factors associated with public attitudes towards persons with disabilities: a systematic review
Authors: Wang Ziru , Xu Xiaoli , Han Qiong , Chen Yan , Jiang Jiayao , Ni Guo-Xin
Published: June 2021

Objective

The aim of this review is to identify and summarize factors that are associated with public attitudes towards people with various disabilities systematically.

Methods

An electronic search of three databases was performed (Medline, EMBASE and Cochrane) covering the period from 1950 to present. A comprehensive search strategy was developed and the lists of citations were screened for potential eligible studies. Only quantitative studies using valid measurements were included, and the methodological quality of included studies was appraised based on three criteria (sample, measurement, analysis) by two independent reviewers.

Results

The initial electronic search yielded 995 articles after duplicates removed, and 27 studies met the eligibility criteria were included in the study. Three categories of the factors were found to be associated with the public attitudes, which are related to the attitude provider, disabled people, and society respectively. Specifically, the more people know about disabilities, the more likely they were to have positive attitude; and the frequency and quality of the contact with the disabled are also proved to be influential to the attitudes. Meanwhile, the type of disability is also closely correlated to the public’s attitude towards the disabilities.

Conclusion

People’s knowledge of the disability and their contact with individuals with disabilities are the main influential factors in public attitudes towards persons with disabilities.
Analysis of endometrial thickness patterns and pregnancy outcomes considering 12,991 fresh IVF cycles
Authors: Liao ShuJie , Wang Renjie , Hu Cheng , Pan Wulin , Pan Wei , Yu Dongyang , Jin Lei
Published: June 2021

Background

Different endometrial patterns have an important effect on the relationship between endometrial thickness (EMT) and clinical pregnancy rate. There is a significant difference in age, selection of cycle protocols, and clinical pregnancy rates among four groups with diverse endometrial patterns.

Methods

This retrospective study aimed to assess the association between EMT on human chorionic gonadotropin (HCG) administration day and the clinical outcome of fresh in vitro fertilization (IVF). The 5th, 50th, and 95th percentiles for EMT were determined as 8, 11, and 14 mm, respectively. Patients were sub-divided into four groups based on their EMT in different endometrial patterns (Group 1: < 8 mm; Group 2: ≥ 8 and ≤ 11 mm; Group 3: > 11 and ≤ 14 mm; Group 4: > 14 mm). We divided patients into three groups based on their endometrial pattern and evaluated the correlation between EMT and clinical pregnancy rate.

Results

We found a positive correlation between pregnancy rates and EMT in all endometrial patterns. Multiple logistic regression analysis proved age, duration of infertility, cycle protocols, number of embryos transferred, progesterone on HCG day, endometrial patterns, and EMT have significant effects on clinical pregnancy rates. Meanwhile, there was a significant difference in age, selection of cycle protocols, and clinical pregnancy rates among four groups with diverse endometrial patterns.

Conclusions

Different endometrial patterns have an important effect on the relationship between EMT and clinical pregnancy rate.
Examining the effect of explanation on satisfaction and trust in AI diagnostic systems
Authors: Alam Lamia , Mueller Shane
Published: June 2021

Background

Artificial Intelligence has the potential to revolutionize healthcare, and it is increasingly being deployed to support and assist medical diagnosis. One potential application of AI is as the first point of contact for patients, replacing initial diagnoses prior to sending a patient to a specialist, allowing health care professionals to focus on more challenging and critical aspects of treatment. But for AI systems to succeed in this role, it will not be enough for them to merely provide accurate diagnoses and predictions. In addition, it will need to provide explanations (both to physicians and patients) about why the diagnoses are made. Without this, accurate and correct diagnoses and treatments might otherwise be ignored or rejected.

Method

It is important to evaluate the effectiveness of these explanations and understand the relative effectiveness of different kinds of explanations. In this paper, we examine this problem across two simulation experiments. For the first experiment, we tested a re-diagnosis scenario to understand the effect of local and global explanations. In a second simulation experiment, we implemented different forms of explanation in a similar diagnosis scenario.

Results

Results show that explanation helps improve satisfaction measures during the critical re-diagnosis period but had little effect before re-diagnosis (when initial treatment was taking place) or after (when an alternate diagnosis resolved the case successfully). Furthermore, initial “global” explanations about the process had no impact on immediate satisfaction but improved later judgments of understanding about the AI. Results of the second experiment show that visual and example-based explanations integrated with rationales had a significantly better impact on patient satisfaction and trust than no explanations, or with text-based rationales alone. As in Experiment 1, these explanations had their effect primarily on immediate measures of satisfaction during the re-diagnosis crisis, with little advantage prior to re-diagnosis or once the diagnosis was successfully resolved.

Conclusion

These two studies help us to draw several conclusions about how patient-facing explanatory diagnostic systems may succeed or fail. Based on these studies and the review of the literature, we will provide some design recommendations for the explanations offered for AI systems in the healthcare domain.
Raised sputum extracellular DNA confers lung function impairment and poor symptom control in an exacerbation-susceptible phenotype of neutrophilic asthma
Authors: Abdo Mustafa , Uddin Mohib , Goldmann Torsten , Marwitz Sebastian , Bahmer Thomas , Holz Olaf , Kirsten Anne-Marie , Trinkmann Frederik , von Mutius Erika , Kopp Matthias , Hansen Gesine , Rabe Klaus F. , Watz Henrik , Pedersen Frauke ,   the ALLIANCE study group
Published: June 2021

Background

Extracellular DNA (e-DNA) and neutrophil extracellular traps (NETs) are linked to asthmatics airway inflammation. However, data demonstrating the characterization of airway inflammation associated with excessive e-DNA production and its impact on asthma outcomes are limited.

Objective

To characterize the airway inflammation associated with excessive e-DNA production and its association with asthma control, severe exacerbations and pulmonary function, particularly, air trapping and small airway dysfunction.

Methods

We measured e-DNA concentrations in induced sputum from 134 asthma patients and 28 healthy controls. We studied the correlation of e-DNA concentrations with sputum neutrophils, eosinophils and macrophages and the fractional exhaled nitric oxide (FeNO). Lung function was evaluated using spirometry, body plethysmography, impulse oscillometry and inert gas multiple breath washout. We stratified patients with asthma into low-DNA and high-DNA to compare lung function impairments and asthma outcomes.

Results

Patients with severe asthma had higher e-DNA concentration (54.2 ± 42.4 ng/µl) than patients with mild-moderate asthma (41.0 ± 44.1 ng/µl) or healthy controls (26.1 ± 16.5 ng/µl), (all p values < 0.05). E-DNA concentrations correlated directly with sputum neutrophils (R = 0.49, p < 0.0001) and negatively with sputum macrophages (R = − 0.36, p < 0.0001), but neither with sputum eosinophils (R = 0.10, p = 0.26), nor with FeNO (R = − 0.10, p = 0.22). We found that 29% of asthma patients (n = 39) had high e-DNA concentrations above the upper 95th percentile value in healthy controls (55.6 ng /μl). High-DNA was associated with broad lung function impairments including: airflow obstruction of the large (FEV1) and small airways (FEF50%, FEF25–75), increased air trapping (RV, RV/TLC), increased small airway resistance (R5-20, sReff), decreased lung elasticity (X5Hz) and increased ventilation heterogeneity (LCI), (all P values < 0.05). We also found that high e-DNA was associated with nearly three-fold greater risk of severe exacerbations (OR 2·93 [95% CI 1.2–7.5]; p = 0·012), worse asthma control test (p = 0.03), worse asthma control questionnaire scores (p = 0.01) and higher doses of inhaled corticosteroids (p = 0.026).

Conclusion

Increased production of extracellular DNA in the airway characterizes a subset of neutrophilic asthma patients who have broad lung function impairments, poor symptom control and increased risk of severe exacerbations.
A novel specific grading standard study of auto-segmentation of organs at risk in thorax: subjective–objective-combined grading standard
Authors: Ying Yanchen , Wang Hao , Chen Hua , Cheng Jianfan , Gu Hengle , Shao Yan , Duan Yanhua , Feng Aihui , Feng Wen , Fu Xiaolong , Quan Hong , Xu Zhiyong
Published: June 2021

Background

To develop a novel subjective–objective-combined (SOC) grading standard for auto-segmentation for each organ at risk (OAR) in the thorax.

Methods

A radiation oncologist manually delineated 13 thoracic OARs from computed tomography (CT) images of 40 patients. OAR auto-segmentation accuracy was graded by five geometric objective indexes, including the Dice similarity coefficient (DSC), the difference of the Euclidean distance between centers of mass (ΔCMD), the difference of volume (ΔV), maximum Hausdorff distance (MHD), and average Hausdorff distance (AHD). The grading results were compared with those of the corresponding geometric indexes obtained by geometric objective methods in the other two centers. OAR auto-segmentation accuracy was also graded by our subjective evaluation standard. These grading results were compared with those of DSC. Based on the subjective evaluation standard and the five geometric indexes, the correspondence between the subjective evaluation level and the geometric index range was established for each OAR.

Results

For ΔCMD, ΔV, and MHD, the grading results of the geometric objective evaluation methods at our center and the other two centers were inconsistent. For DSC and AHD, the grading results of three centers were consistent. Seven OARs’ grading results in the subjective evaluation standard were inconsistent with those of DSC. Six OARs’ grading results in the subjective evaluation standard were consistent with those of DSC. Finally, we proposed a new evaluation method that combined the subjective evaluation level of those OARs with the range of corresponding DSC to determine the grading standard. If the DSC ranges between the adjacent levels did not overlap, the DSC range was used as the grading standard. Otherwise, the mean value of DSC was used as the grading standard.

Conclusions

A novel OAR-specific SOC grading standard in thorax was developed. The SOC grading standard provides a possible alternative for evaluation of the auto-segmentation accuracy for thoracic OARs.
Change in health spending after implementation of a health transformation plan in Iran: an interrupted time series analysis
Authors: Esmaeili Reza , Rouhani Samad , Yazdani Charati Jamshid , Khandehroo Masoud
Published: June 2021

Background

Health transformation plan (HTP) implemented in Iran since 2014 to improve accessibility and financial protection of patients. This study aimed to assess the impact of HTP on health spending in Iran.

Methods

This was a quasi-experimental design using Interrupted Time Series. All registered impatient records in Iran health insurance organization (IHIO) for the population of Mazandaran province (1,628,919 population in 2011), north of Iran from March 2010 to February 2019 were included. Data for three depended variables: hospitalization rate, average inpatient cost and inpatient expenditure per capita was extracted in 96 monthly observations. Segmented regression analysis was done in R version 3.6.1.

Results

Hospitalization rate in 2010 was 6.6 in 1000 people and its level change was 0/799 immediately after HTP (P < 001). Post-reform level and trend changes for monthly average inpatient cost of registered admissions in IHIO were also significant (P < 001). IHIO inpatient expenditure per capita for 1,628,919 population in Mazandaran province was 24,436 Rials in 2011 and increased significantly immediately following HTP as 34,459 Rials (P < 001).

Conclusions

Three important components of health spending including hospitalization rate, average inpatient cost and inpatient expenditure per capita were increased dramatically after HTP. Cost containment strategies and strengthening the preventive care initiatives is required to control the escalating trends of inpatient expenditure in Iran.
Correction to: The urgency of utilizing COVID-19 biospecimens for research in the heart of the global pandemic
Authors: Osman Iman , Cotzia Paolo , Moran Una , Donnelly Douglas , Arguelles-Grande Carolina , Mendoza Sandra , Moreira Andre
Published: June 2021

An amendment to this paper has been published and can be accessed via the original article.
Oxidative stress response in regulatory and conventional T cells: a comparison between patients with chronic coronary syndrome and healthy subjects
Authors: Lundberg Anna K. , Chung Rosanna W. S. , Zeijlon Louise , Fernström Gustav , Jonasson Lena
Published: June 2021

Background

Inflammation and oxidative stress form a vicious circle in atherosclerosis. Oxidative stress can have detrimental effects on T cells. A unique subset of CD4+T cells, known as regulatory T (Treg) cells, has been associated with atheroprotective effects. Reduced numbers of Tregcells is a consistent finding in patients with chronic coronary syndrome (CCS). However, it is unclear to what extent these cells are sensitive to oxidative stress. In this pilot study, we tested the hypothesis that oxidative stress might be a potential contributor to the Tregcell deficit in CCS patients.

Methods

Thirty patients with CCS and 24 healthy controls were included. Treg(CD4+CD25+CD127−) and conventional T (CD4+CD25−, Tconv) cells were isolated and treated with increasing doses of H2O2. Intracellular ROS levels and cell death were measured after 2 and 18 h, respectively. The expression of antioxidant genes was measured in freshly isolated Tregand Tconvcells. Also, total antioxidant capacity (TAC) was measured in fresh peripheral blood mononuclear cells, and oxidized (ox) LDL/LDL ratios were determined in plasma.

Results

At all doses of H2O2,Tregcells accumulated more ROS and exhibited higher rates of death than their Tconvcounterparts, p < 0.0001. Tregcells also expressed higher levels of antioxidant genes, including thioredoxin and thioredoxin reductase-1 (p < 0.0001), though without any differences between CCS patients and controls. Tconvcells from CCS patients were, on the other hand, more sensitive to oxidative stress ex vivo and expressed more thioredoxin reductase-1 than Tconvcells from controls, p < 0.05. Also, TAC levels were lower in patients, 0.97 vs 1.53 UAE/100 µg, p = 0.001, while oxLDL/LDL ratios were higher, 29 vs 22, p = 0.006.

Conclusion

Tregcells isolated from either CCS patients or healthy controls were all highly sensitive to oxidative stress ex vivo. There were signs of oxidant-antioxidant imbalance in CCS patients and we thus assume that oxidative stress may play a role in the reduction of Tregcells in vivo.
Multiple synaptic connections into a single cortical pyramidal cell or interneuron in the anterior cingulate cortex of adult mice
Authors: Lee Jung-Hyun Alex , Miao Zhuang , Chen Qi-Yu , Li Xu-Hui , Zhuo Min
Published: June 2021

The ACC is an important brain area for the processing of pain-related information. Studies of synaptic connections within the ACC provide an understanding of basic cellular and molecular mechanisms for brain functions such as pain, emotion and related cognitive functions. Previous study of ACC synaptic transmission mainly focused on presumably thalamic inputs into pyramidal cells. In the present study, we developed a new mapping technique by combining single neuron whole-cell patch-clamp recording with 64 multi-channel field potential recording (MED64) to examine the properties of excitatory inputs into a single neuron in the ACC. We found that a single patched pyramidal neuron or interneuron simultaneously received heterogeneous excitatory synaptic innervations from different subregions (ventral, dorsal, deep, and superficial layers) in the ACC. Conduction velocity is faster as stimulation distance increases in pyramidal neurons. Fast-spiking interneurons (FS-IN) show slower inactivation when compared to pyramidal neurons and regular-spiking interneurons (RS-IN) while pyramidal neurons displayed the most rapid activation. Bath application of non-competitive AMPA receptor antagonist GYKI 53655 followed by CNQX revealed that both FS-INs and RS-INs have AMPA and KA mediated components. Our studies provide a new strategy and technique for studying the network of synaptic connections.
Atg7 deficiency in microglia drives an altered transcriptomic profile associated with an impaired neuroinflammatory response
Authors: Friess Lara , Cheray Mathilde , Keane Lily , Grabert Kathleen , Joseph Bertrand
Published: June 2021

Microglia, resident immunocompetent cells of the central nervous system, can display a range of reaction states and thereby exhibit distinct biological functions across development, adulthood and under disease conditions. Distinct gene expression profiles are reported to define each of these microglial reaction states. Hence, the identification of modulators of selective microglial transcriptomic signature, which have the potential to regulate unique microglial function has gained interest. Here, we report the identification of ATG7 (Autophagy-related 7) as a selective modulator of an NF-κB-dependent transcriptional program controlling the pro-inflammatory response of microglia. We also uncover that microglialAtg7-deficiency was associated with reduced microglia-mediated neurotoxicity, and thus a loss of biological function associated with the pro-inflammatory microglial reactive state. Further, we show thatAtg7-deficiency in microglia did not impact on their ability to respond to alternative stimulus, such as one driving them towards an anti-inflammatory/tumor supportive phenotype. The identification of distinct regulators, such asAtg7, controlling specific microglial transcriptional programs could lead to developing novel therapeutic strategies aiming to manipulate selected microglial phenotypes, instead of the whole microglial population with is associated with several pitfalls.
Determination of calcium and parathyroid hormone levels following hemithyroidectomy
Authors: Palop Isabel Fernández , Martínez Cristina Fernández , Giménez María Jesús Segura , Azorin Samper M. Carmen , Fuster Rafael García
Published: June 2021

Background and objective

Hypocalcemia is one of the main complications of thyroid surgery. We hypothesized that hemithyroidectomy may have an impact on serum parathyroid hormone (PTH) and calcium levels despite only one thyroid lobe is manipulated. The objective of this study was to analyze changes in serum PTH and calcium levels following hemithyroidectomy.

Methods

This is a prospective study of 53 patients who underwent thyroid lobectomy. The serum PTH level was determined in the preoperative period, 15 min after extraction of the surgical specimen, and 24 h and 3 weeks after surgery. Serum ionized calcium was also measured in the preoperative period and at 6 h, 24 h and 3 weeks after surgery. We assessed the postoperative calcium value and its relationship with the extent of fall in PTH levels in the postoperative period.

Results

None of the patients had the postoperative serum ionised calcium level less than 4 mg/dl. The decrease in postoperative calcium was statistically significant at 6 and 24 h after surgery; there was no difference at 3 weeks post-surgery. The change in post-operative serum PTH levels followed a similar trend to postoperative serum calcium levels.

Conclusions

Although serum calcium level decreased after a lobectomy, it always remained above 4 mg/dl. We conclude that hypocalcaemia is rare following hemithyroidectomy.
Smartphone apps to support laypersons in bystander CPR are of ambivalent benefit: a controlled trial using medical simulation
Authors: Metelmann Camilla , Metelmann Bibiana , Schuffert Louisa , Hahnenkamp Klaus , Vollmer Marcus , Brinkrolf Peter
Published: June 2021

Background

Bystander-initiated resuscitation is essential for surviving out-of-hospital cardiac arrest. Smartphone apps can provide real-time guidance for medical laypersons in these situations. Are these apps a beneficial addition to traditional resuscitation training?

Methods

In this controlled trial, we assessed the impact of app use on the quality of resuscitation (hands-off time, assessment of the patient’s condition, quality of chest compression, body and arm positioning). Pupils who have previously undergone a standardised resuscitation training, encountered a simulated cardiac arrest either (i) without an app (control group); (ii) with facultative app usage; or (iii) with mandatory app usage. Measurements were compared using generalised linear regression.

Results

200 pupils attended this study with 74 pupils in control group, 65 in facultative group and 61 in mandatory group. Participants who had to use the app significantly delayed the check for breathing, call for help, and first compression, leading to longer total hands-off time. Hands-off time during chest compression did not differ significantly. The percentage of correct compression rate and correct compression depth was significantly higher when app use was mandatory. Assessment of the patient’s condition, and body and arm positioning did not differ.

Conclusions

Smartphone apps offering real-time guidance in resuscitation can improve the quality of chest compression but may also delay the start of resuscitation. Provided that the app gives easy-to-implement, guideline-compliant instructions and that the user is familiar with its operation, we recommend smartphone-guidance as an additional tool to hands-on CPR-training to increase the prevalence and quality of bystander-initiated CPR.
Unmatched ventilation and perfusion measured by electrical impedance tomography predicts the outcome of ARDS
Authors: Spinelli Elena , Kircher Michael , Stender Birgit , Ottaviani Irene , Basile Maria C. , Marongiu Ines , Colussi Giulia , Grasselli Giacomo , Pesenti Antonio , Mauri Tommaso
Published: June 2021

Background

In acute respiratory distress syndrome (ARDS), non-ventilated perfused regions coexist with non-perfused ventilated regions within lungs. The number of unmatched regions might reflect ARDS severity and affect the risk of ventilation-induced lung injury. Despite pathophysiological relevance, unmatched ventilation and perfusion are not routinely assessed at the bedside. The aims of this study were to quantify unmatched ventilation and perfusion at the bedside by electrical impedance tomography (EIT) investigating their association with mortality in patients with ARDS and to explore the effects of positive end-expiratory pressure (PEEP) on unmatched ventilation and perfusion in subgroups of patients with different ARDS severity based on PaO2/FiO2 and compliance.

Methods

Prospective observational study in 50 patients with mild (36%), moderate (46%), and severe (18%) ARDS under clinical ventilation settings. EIT was applied to measure the regional distribution of ventilation and perfusion using central venous bolus of saline 5% during end-inspiratory pause. We defined unmatched units as the percentage of only ventilated units plus the percentage of only perfused units.

Results

Percentage of unmatched units was significantly higher in non-survivors compared to survivors (32[27–47]% vs. 21[17–27]%, p < 0.001). Percentage of unmatched units was an independent predictor of mortality (OR 1.22, 95% CI 1.07–1.39, p = 0.004) with an area under the ROC curve of 0.88 (95% CI 0.79–0.97, p < 0.001). The percentage of ventilation to the ventral region of the lung was higher than the percentage of ventilation to the dorsal region (32 [27–38]% vs. 18 [13–21]%, p < 0.001), while the opposite was true for perfusion (28 [22–38]% vs. 36 [32–44]%, p < 0.001).

Higher percentage of only perfused units was correlated with lower dorsal ventilation (r =  − 0.486, p < 0.001) and with lower PaO2/FiO2 ratio (r =  − 0.293, p = 0.039).

Conclusions

EIT allows bedside assessment of unmatched ventilation and perfusion in mechanically ventilated patients with ARDS. Measurement of unmatched units could identify patients at higher risk of death and could guide personalized treatment.
Targeted mutagenesis in mouse cells and embryos using an enhanced prime editor
Authors: Park Soo-Ji , Jeong Tae Yeong , Shin Seung Kyun , Yoon Da Eun , Lim Soo-Yeon , Kim Sol Pin , Choi Jungmin , Lee Hyunji , Hong Jeong-Im , Ahn Jinhee , Seong Je Kyung , Kim Kyoungmi
Published: June 2021

Prime editors, novel genome-editing tools consisting of a CRISPR-Cas9 nickase and an engineered reverse transcriptase, can induce targeted mutagenesis. Nevertheless, much effort is required to optimize and improve the efficiency of prime-editing. Herein, we introduce two strategies to improve the editing efficiency using proximal dead sgRNA and chromatin-modulating peptides. We used enhanced prime-editing to generateIgf2mutant mice with editing frequencies of up to 47% and observed germline transmission, no off-target effects, and a dwarf phenotype. This improved prime-editing method can be efficiently applied to cell research and to generate mouse models.
Synthesis of 4,4′-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols) and evaluation of their antioxidant and anticancer activities
Authors: Cadena-Cruz José Eduardo , Guamán-Ortiz Luis M. , Romero-Benavides Juan Carlos , Bailon-Moscoso Natalia , Murillo-Sotomayor Kevin E. , Ortiz-Guamán Nadia V. , Heredia-Moya Jorge
Published: June 2021

Background

Pyrazoles have attracted particular attention due to the diverse biological activities associated with this heterocyclic system, and some have been shown to be cytotoxic to several human cell lines. Several drugs currently on the market have this heterocycle as the key structural motif, and some have been approved for the treatment of different types of cancer.

Results

4,4ʹ-(Arylmethylene)bis(1H-pyrazol-5-ols) derivatives 3a–q were synthetized by a three components reaction of 3-methyl-1-phenyl-5-pyrazolone (1) with various benzaldehydes 2 catalyzed by sodium acetate at room temperature. The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR) and were evaluated for their radical scavenging activity by DPPH assay and tested in vitro on colorectal RKO carcinoma cells in order to determine their cytotoxic properties. All 4,4ʹ-(arylmethylene)bis(1H-pyrazol-5-ols) derivatives 3a–q were synthetized in high to excellent yield, and pure products were isolated by simple filtration. All compounds have good radical scavenging activity, and half of them are more active than ascorbic acid used as standard.

Conclusion

Several derivatives proved to be cytotoxic in the RKO cell line. In particular, compound 3i proved to be a very potent scavenger with an IC50 of 6.2 ± 0.6 µM and exhibited an IC50 of 9.9 ± 1.1 μM against RKO cell. Autophagy proteins were activated as a survival mechanism, whereas the predominant pathway of death was p53-mediated apoptosis.
Losing DNA methylation at repetitive elements and breaking bad
Authors: Pappalardo Xena Giada , Barra Viviana
Published: June 2021

Background

DNA methylation is an epigenetic chromatin mark that allows heterochromatin formation and gene silencing. It has a fundamental role in preserving genome stability (including chromosome stability) by controlling both gene expression and chromatin structure. Therefore, the onset of an incorrect pattern of DNA methylation is potentially dangerous for the cells. This is particularly important with respect to repetitive elements, which constitute the third of the human genome.

Main body

Repetitive sequences are involved in several cell processes, however, due to their intrinsic nature, they can be a source of genome instability. Thus, most repetitive elements are usually methylated to maintain a heterochromatic, repressed state. Notably, there is increasing evidence showing that repetitive elements (satellites, long interspersed nuclear elements (LINEs), Alus) are frequently hypomethylated in various of human pathologies, from cancer to psychiatric disorders. Repetitive sequences’ hypomethylation correlates with chromatin relaxation and unscheduled transcription. If these alterations are directly involved in human diseases aetiology and how, is still under investigation.

Conclusions

Hypomethylation of different families of repetitive sequences is recurrent in many different human diseases, suggesting that the methylation status of these elements can be involved in preservation of human health. This provides a promising point of view towards the research of therapeutic strategies focused on specifically tuning DNA methylation of DNA repeats.
Modified formulas for calculation of encephalization: quotient in dogs
Authors: Saganuwan Saganuwan Alhaji
Published: June 2021

Objective

Dogs are a breed of animals that play important roles in security service, companionship, hunting, guard, work and models of research for application in humans. Intelligence is the key factor to success in life, most especially for dogs that are used for security purposes at the airports, seaports, public places, houses, schools and farms. However, it has been reported that there is correlation between intelligence, body weight, height and craniometry in human. In view of this, literatures were searched on body weight, height and body surface areas of ten dogs with intent to determining their comparative level of intelligence using encephalization quotient.

Results

Findings revealed that dogs have relationship of brain allometry with human as proven by encephalization quotient $$\left( {{\text{EQ}}} \right)\, = \,{\text{Brain Mass}}/0.{14}\, \times \,{\text{Body weight}}^{{0.{528}}} ,{\text{ Brain Mass}}/0.{12}\, \times \,{\text{Body Weight}}^{{0.{66}}}$$

EQ

=

Brain Mass

/
0.14

×

Body weight

0.528

,

Brain Mass

/
0.12

×

Body Weight

0.66

and Brain Mass (E)  =  kpβ, where p is the body weight; k  =  0.14 and β = 0.528, respectively. Saganuwa’s formula yielded better results as compared with the other formulas. Dogs with body surface area (BSA), weight and height similar to that of human are the most intelligent. Doberman pinscher is the most intelligent followed by German shepherd, Labrador retriever, Golden retriever, respectively.
Examining the relationship between interpersonal support and retention in HIV care among HIV+ nursing mothers in Uganda
Authors: Nutor Jerry John , Agbadi Pascal , Hoffmann Thomas J. , Anguyo Geoffrey , Camlin Carol S.
Published: June 2021

Objective

The global burden of HIV on women and pediatric populations are severe in sub-Saharan Africa. Global child HIV infection rates have declined, but this rate remains quite high in sub-Saharan Africa due to Mother-to-child transmission (MTCT). To prevent MTCT of HIV, postpartum women living with HIV (WLHIV) are required to return to a health facility for HIV care within 60 days after childbirth (Retention in HIV care). Studies suggest that interpersonal support was positively associated with retention in HIV care. However, information on this association is lacking among postpartum WLHIV in Uganda. Therefore, this study investigates the relationship between interpersonal support, measured with the Interpersonal Support Evaluation List (ISEL-12), and retention in HIV care.

Results

In a total of 155 postpartum WLHIV, 84% were retained in HIV care. ISEL-12 was negatively associated with retention in HIV care. Postpartum WLHIV retained in care (24.984 ± 4.549) have lower ISEL-12 scores compared to the non-retained group (27.520 ± 4.224), t(35.572) = − 2.714, p = 0.01. In the non-income earning sample, respondents retained in care (24.110 ± 4.974) have lower ISEL scores compared to the non-retained group (27.000 ± 4.855), t(20.504) = -2.019, p = 0.049. This was not significant among income earning WLHIV.