Search

This study proposes the comprehensive index of biomarker (CIB), based on the consistency of a biomarker in case control (Youden index, J) and cohort studies (Crc), to evaluate biomarker efficacy. CIB was calculated as the mean of J and Crc. Analysis of the effect of sensitivity and specificity on CIB and ROC analysis of CIB were performed in simulated and actual datasets. J and CIB had similar values for high-probability events (say probability was 0.50), but there was a significant difference between J and CIB for low-probability events (say probability was 0.05). Therefore, as the subjects considered for diagnosis are usually symptomatic, the occurrence of a disease can be assumed to be a high-probability event. In contrast, as the subjects considered in screening for a disease are usually healthy and asymptomatic, the occurrence of a disease is assumed to be a low-probability event. Although J is the common index used to evaluate the diagnostic effectiveness, unfortunately, the J value is significantly larger than CIB value in a low-probability event, showing overestimation for screening purpose. CIB could have more potential than J for determining the screening efficacy of a biomarker. The efficacy of a biomarker could differ for diagnostic, screening, predictive, and prognostic purposes, and it would be better to evaluate the efficacy of biomarkers for specific systems or contexts.

Our aim was to investigate whether the previously observed higher contrast-to-noise ratio (CNR) and better image quality of Digital Variance Angiography (DVA) - compared to Digital Subtraction Angiography (DSA) - can be used to reduce radiation exposure in lower limb X-ray angiography. This prospective study enrolled 30 peripheral artery disease patients (mean ± SD age 70 ± 8 years) undergoing diagnostic angiography. In all patients, both normal (1.2 µGy/frame; 100%) and low-dose (0.36 µGy/frame; 30%) protocols were used for the acquisition of images in three anatomical regions (abdominal, femoral, crural). The CNR of DSA and DVA images were calculated, and the visual quality was evaluated by seven specialists using a 5-grade Likert scale. For investigating non-inferiority, the difference of low-dose DVA and normal dose DSA scores (DVA30-DSA100) was analyzed. DVA produced two- to three-fold CNR and significantly higher visual score than DSA. DVA30 proved to be superior to DSA100 in the crural region (difference 0.25 ± 0.07, p p = 0.435) and abdominal (− 0.10 ± 0.09, p = 0.350) regions. Our data show that DVA allows about 70% reduction of DSA-related radiation exposure in lower limb X-ray angiography, providing a potential new radiation protection tool for the patients and the medical staff.

This study compared macular capillary parameters between healthy black and white subjects using optical coherence tomography angiography (OCTA). We measured vessel density (VD) of superficial (SCP), intermediate (ICP), and deep (DCP) capillary plexuses and choriocapillaris blood flow area (BFA) of the fovea, parafovea and total 3 mm-diameter circular area centered on the fovea, as well as the foveal avascular zone (FAZ) parameters, controlling for axial length. Black subjects had lower foveal and parafoveal VD in the SCP (p = 0.043 and p = 0.014) and the ICP (p = 0.014 and p = 0.002). In the DCP, black subjects had a trend toward lower foveal and parafoveal VD. Black subjects had decreased choriocapillaris BFA in the total 3 mm area (p = 0.011) and the parafovea (p = 0.033), larger FAZ area (p = 0.006) and perimeter (p = 0.014), and a higher capillary density in a 300 μm wide region around the FAZ (FD-300) (p = 0.001). There was no significant difference in FAZ acircularity index. To our knowledge, this is the first report analyzing the three distinct retinal capillary plexuses and identifying differing baseline VD, choriocapillaris and FAZ parameters in healthy young black compared to white subjects. Larger studies are needed to validate these findings and better understand racial differences in vulnerability to ocular diseases.

The association between the footwear microclimate and microbial community on the foot plantar skin was investigated by experiments with three participants. Novel methods were developed for measuring in-shoe temperature and humidity at five footwear regions, as well as the overall ventilation rate inside the footwear. Three types of footwear were tested including casual shoes, running shoes, and perforated shoes for pairwise comparison of footwear microclimate and corresponding microbial community on the skin. The major findings are as follows: (1) footwear types make a significant difference to in-shoe temperature at the instep region with the casual shoes sustaining the warmest of all types; (2) significant differences were observed in local internal absolute humidity between footwear types, with the casual shoes sustaining the highest level of humidity at most regions; (3) the perforated shoes provided the highest ventilation rate, followed by running and casual shoes, and the faster the gait, the larger the discrepancy in ventilation rate between footwear types; (4) the casual shoes seemed to provide the most favorable internal environment for bacterial growth at the distal plantar skin; and (5) the bacterial growth at the distal plantar skin showed a positive linear correlation with the in-shoe temperature and absolute humidity, and a negative linear correlation with the ventilation rate. The ventilation rate seemed to be a more reliable indicator of the bacterial growth. Above all, we can conclude that footwear microclimate varies in footwear types, which makes contributions to the bacterial growth on the foot plantar skin.

Even a tiny functioning pituitary adenoma could cause symptoms; hence, accurate diagnosis and treatment are crucial for management. However, it is difficult to diagnose a small pituitary adenoma using conventional MR sequence. Deep learning-based reconstruction (DLR) using magnetic resonance imaging (MRI) enables high-resolution thin-section imaging with noise reduction. In the present single-institution retrospective study of 201 patients, conducted between August 2019 and October 2020, we compared the performance of 1 mm DLR MRI with that of 3 mm routine MRI, using a combined imaging protocol to detect and delineate pituitary adenoma. Four readers assessed the adenomas in a pairwise fashion, and diagnostic performance and image preferences were compared between inexperienced and experienced readers. The signal-to-noise ratio (SNR) was quantitatively assessed. New detection of adenoma, achieved using 1 mm DLR MRI, was not visualised using 3 mm routine MRI (overall: 6.5% [13/201]). There was no significant difference depending on the experience of the readers in new detections. Readers preferred 1 mm DLR MRI over 3 mm routine MRI (overall superiority 56%) to delineate normal pituitary stalk and gland, with inexperienced readers more preferred 1 mm DLR MRI than experienced readers. The SNR of 1 mm DLR MRI was 1.25-fold higher than that of the 3 mm routine MRI. In conclusion, the 1 mm DLR MRI achieved higher sensitivity in the detection of pituitary adenoma and provided better delineation of normal pituitary gland than 3 mm routine MRI.

The purpose of the present study was to analyze normal and degenerated menisci with Raman methodology on thin sections of formalin fixed paraffin embedding tissues and to correlate the Raman findings with the grade of meniscus degeneration. Menisci (n = 27) were removed from human knee joints after total knee replacement or meniscectomy. Following routine histopathological analysis to determine the grade of meniscal lesions obtained from healthy and degenerated formaline fixed paraffin embedded (FFPE) meniscal sections, Raman polarization approach was applied to evaluate the orientation of collagen fibrils in different levels of the same 5 μm thick FFPE meniscal tissue sections, used for histopathological assessment. We collected Raman spectra in two different polarization geometries, v-HH and v-VV, and calculated the mean value of the v-HH/v-VV intensity ratio of two Raman bands, sensitive and non-sensitive to the molecular orientation. The collagen specific amide I band at 1665 cm−1, has the higher sensitivity dependence on the Raman polarization. The mean values of ratio v-HH/v-VV of the 1665 cm−1 peak intensity was significantly higher in healthy, mean ± SD: 2.56 ± 0.46, compared to degenerated menisci, mean ± SD: 1.85 ± 0.42 (p = 0.0014). The mean values of v-HH/v-VV intensity ratio were 2.18 and 1.50 for low and high degenerated menisci, respectively (p

Purpose: To examine the refractive lens power (RLP) and lens thickness and their associated factors in children from North-Western China.Methods: Children from two schools (primary school and junior high school) in the North-Western Chinese province of Qinghai underwent a comprehensive ophthalmic examination including biometry and cycloplegic refractometry. The RLP was calculated using Bennett’s equation. Results: The study included 596 (77.9%) individuals (mean age: 11.0±2.8 years; range: 6-16 years) with a mean axial length of 23.65±1.24mm (range: 20.02-27.96mm). Mean lens thickness was 3.30±0.16mm (range: 2.85-3.99mm) and mean RLP was 24.85±1.98D (range: 19.40-32.97). In univariate analysis, girls as compared to boys had a significantly thicker lens and greater RLP, shorter axial length, smaller corneal curvature radius and shorter corneal curvature radius (all PP=0.11) and corneal thickness (P=0.16). RLP was positively associated with refractive error (correlation coefficient r=0.33; PPPPβ=−0.07), female sex (Pβ=−0.08), shorter axial length (Pβ=−0.48) and higher lens thickness (Pβ=0.42). Conclusions: In Chinese children, RLP with a mean of 24.85±1.98D decreases with older age, male sex, longer axial length, and thinner lens thickness. Changes in RLP and axial length elongation are important players in the emmetropization and myopization.

To determine whether temporal subtraction (TS) CT obtained with non-rigid image registration improves detection of various bone metastases during serial clinical follow-up examinations by numerous radiologists. Six board-certified radiologists retrospectively scrutinized CT images for patients with history of malignancy sequentially. These radiologists selected 50 positive and 50 negative subjects with and without bone metastases, respectively. Furthermore, for each subject, they selected a pair of previous and current CT images satisfying predefined criteria by consensus. Previous images were non-rigidly transformed to match current images and subtracted from current images to automatically generate TS images. Subsequently, 18 radiologists independently interpreted the 100 CT image pairs to identify bone metastases, both without and with TS images, with each interpretation separated from the other by an interval of at least 30 days. Jackknife free-response receiver operating characteristics (JAFROC) analysis was conducted to assess observer performance. Compared with interpretation without TS images, interpretation with TS images was associated with a significantly higher mean figure of merit (0.710 vs. 0.658; JAFROC analysis, P = 0.0027). Mean sensitivity at lesion-based was significantly higher for interpretation with TS compared with that without TS (46.1% vs. 33.9%; P = 0.003). Mean false positive count per subject was also significantly higher for interpretation with TS than for that without TS (0.28 vs. 0.15; P

The long-term results of surgical treatment of intermittent exotropia (X(T)) according to the type of surgery are controversial. We conducted a retrospective cohort study to compare the long-term results between unilateral recession-resection (RR) and bilateral lateral rectus recession (BLR) with an average follow-up of 9.5 years in children with basic-type X(T). Patients with basic-type X(T), who underwent RR (RR group) or BLR (BLR group) and were followed-up for more than 5 years postoperatively, were analyzed. Of the 560 patients, 363 patients received BLR and 197 patients underwent RR. There was no significant difference in the success rates between the two groups until postoperative 3 years. At an average of 9.5 ± 2.6 years after surgery, the success rate of the RR group was significantly higher than that of the BLR group starting from the fourth post-operative year until the last follow-up examination (64.5% vs 43.3%, P 5 prism diopters, and the type of surgery (BLR) were risk factors of recurrence. In conclusion, RR was more successful than BLR with a lower recurrence rate in the long-term follow-up of patients with basic-type X(T).

The genetic characteristics of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) in the Japanese population is unclear. This study aims to investigate the genetic characteristics from nondysplastic BE (NDBE) to early EAC in Japan. Clinical information was collected. Moreover, the genetic profile of NDBE without concurrent dysplasia, early EAC, and surrounding BE were also investigated using endoscopic biopsy samples and formalin-fixed, paraffin-embedded specimens from Japanese patients by targeted next-generation sequencing. Immunohistochemical staining for p53 was also performed for EAC lesions. Targeted NGS was performed for 33 cases with 77 specimens. No significant difference exists in the NDBE group between the number of putative drivers per lesion in the short-segment Barrett’s esophagus (SSBE) and long-segment Barrett’s esophagus (LSBE) [0 (range, 0–1) vs. 0 (range, 0–1). p = 1.00]. TP53 putative drivers were found in two patients (16.7%) with nondysplastic SSBE. TP53 was the majority of putative drivers in both BE adjacent to EAC and EAC, accounting for 66.7% and 66.7%, respectively. More putative drivers per lesion were found in the EAC than in the NDBE group [1 (range, 0–3) vs. 0 (range, 0–1). p TP53 in the Japanese early EAC were similar to those in western countries. However, TP53 putative drivers were detected even in Japanese patients with nondysplastic SSBE. This is significant because such nondysplastic SSBE might have higher risk of progressing to high-grade dysplasia or EAC. The risks of progression may not be underestimated and appropriate follow-ups may be necessary even in patients with SSBE.Trial registration: This study was registered at the University Hospital Medical Information Network (UMIN000034247).

Diffusion-weighted imaging (DWI) is proven useful to differentiate benign and malignant soft tissue tumors (STTs). Radiomics utilizing a vast array of extracted imaging features has a potential to uncover disease characteristics. We aim to assess radiomics using DWI can outperform the conventional DWI for STT differentiation. In 151 patients with 80 benign and 71 malignant tumors, ADCmean and ADCmin were measured on solid portion within the mass by two different readers. For radiomics approach, tumors were segmented and 100 original radiomic features were extracted on ADC map. Eight radiomics models were built with training set (n = 105), using combinations of 2 different algorithms—multivariate logistic regression (MLR) and random forest (RF)—and 4 different inputs: radiomics features (R), R + ADCmin (I), R + ADCmean (E), R + ADCmin and ADCmean (A). All models were validated with test set (n = 46), and AUCs of ADCmean, ADCmin, MLR-R, RF-R, MLR-I, RF-I, MLR-E, RF-E, MLR-A and RF-A models were 0.729, 0.753 0.698, 0.700, 0.773, 0.807, 0.762, 0.744, 0.773 and 0.807, respectively, without statistically significant difference. In conclusion, radiomics approach did not add diagnostic value to conventional ADC measurement for differentiating benign and malignant STTs.

Periodontal disease is a chronic inflammatory condition that affects various peripheral organs. The periodontal inflamed surface area (PISA) quantifies periodontitis severity and the spread of inflammatory wounds. This study aimed to investigate the association between PISA and high-sensitivity C-reactive protein (hs-CRP), a systemic inflammation marker. This study included 250 community-dwelling septuagenarians (69–71 years). We collected information on their medical (e.g., diabetes and dyslipidemia) and dental examinations (e.g., measurement of the probing pocket depth). Generalized linear model analysis was used to explore the association between PISA and hs-CRP levels. There was a significant difference in hs-CRP levels between groups with PISA ≥ 500 and

We investigate the association of incremental pulse wave velocity (ΔC; the change in pulse wave velocity over a cardiac cycle) with cardiometabolic risk factors and report the first and (currently) the largest population-level data. In a cross-sectional study performed in a cohort of 1373 general population participants, ΔC was measured using clinically validated ARTSENS devices. There were 455 participants in the metabolic syndrome (MetS) group whose average ΔC was ~ 28.4% higher than that of the non-metabolic syndrome (Non-MetS) group. Females with MetS showed ~ 10.9% elevated average ΔC compared to males of the Non-MetS group. As the number of risk factors increased from 0 to 5, the average ΔC escalated by ~ 55% (1.50 ± 0.52 m/s to 2.33 ± 0.91 m/s). A gradual increase in average ΔC was observed across each decade from the younger (ΔC = 1.53 ± 0.54 m/s) to geriatric (ΔC = 2.34 ± 0.59 m/s) populations. There was also a significant difference in ΔC among the blood pressure categories. Most importantly, ΔC ≥ 1.81 m/s predicted a constellation of ≥ 3 risks with AUC = 0.615, OR = 2.309, and RR = 1.703. All statistical trends remained significant, even after adjusting for covariates. The study provides initial evidence for the potential use of ΔC as a tool for the early detection and screening of vascular dysfunction, which opens up avenues for active clinical and epidemiological studies. Further investigations are encouraged to confirm and establish the causative mechanism for the reported associations.

Stretch-induced residual force enhancement (rFE) is associated with increased performance in a stretch–shortening cycle (SSC). Although the influence of different range of motions and muscle–tendon unit lengths has been investigated in pure stretch-hold experiments in vivo, the contribution to a SSC movement in human muscles remains unclear. In two sessions, 25 healthy participants performed isometric reference (ISO), shortening hold (SHO) and SSC contractions on an isokinetic dynamometer. We measured the net knee-joint torque, rotational mechanical work, knee kinematics and fascicle behavior (m. vastus lateralis) of the upper right leg. In session 1 the SHO- and SSC-magnitude was changed respectively (SHO: 50°–20°, 80°–20° and 110°–20°; SSC: 20°–50°–20°, 20°–80°–20° and 20°–110°–20°) and in session 2 the muscle–tendon unit length (SHO: 50°–20°, 80°–50° and 110°–80°; SSC: 20°–50°–20°, 50°–80°–50° and 80°–110°–80°; straight leg = 0°). In both sessions, rotational work was significantly (p p

Recent researches have provided evidence that stimulus-driven attentional bias for threats can be modulated by top-down goals. However, it is highlight essential to indicate whether and to what extent the top-down goals can affect the early stage of attention processing and its early neural mechanism. In this study, we collected electroencephalographic data from 28 healthy volunteers with a modified spatial cueing task. The results revealed that in the irrelevant task, there was no significant difference between the reaction time (RT) of the fearful and neutral faces. In the relevant task, we found that RT of fearful faces was faster than that of neutral faces in the valid cue condition, whereas the RT of fearful faces was slower than that of neutral faces in the invalid cue condition. The N170 component in our study showed a similar result compared with RT. Specifically, we noted that in the relevant task, fearful faces in the cue position of the target evoked a larger N170 amplitude than neutral faces, whereas this effect was suppressed in the irrelevant task. These results suggest that the irrelevant task may inhibit the early attention allocation to the fearful faces. Furthermore, the top-down goals can modulate the early attentional bias for threatening facial expressions.

Tumor spread through air spaces (STAS) in non-small-cell lung cancer (NSCLC) is known to influence a poor patient outcome, even in patients presenting with early-stage disease. However, the pre-operative diagnosis of STAS remains challenging. With the progress of radiomics-based analyses several attempts have been made to predict STAS based on radiological findings. In the present study, patients with NSCLC which is located peripherally and tumors ≤ 2 cm in size on computed tomography (CT) that were potential candidates for sublobar resection were enrolled in this study. The radiologic features of the targeted tumors on thin-section CT were extracted using the PyRadiomics v3.0 software package, and a predictive model for STAS was built using the t-test and XGBoost. Thirty-five out of 226 patients had a STAS histology. The predictive model of STAS indicated an area under the receiver-operator characteristic curve (AUC) of 0.77. There was no significant difference in the overall survival (OS) for lobectomy between the predicted-STAS (+) and (−) groups (p = 0.19), but an unfavorable OS for sublobar resection was indicated in the predicted-STAS (+) group (p

Although favourable surgical outcomes for myelopathy caused by cervical ossification of the posterior longitudinal ligament (OPLL) have been reported, factors significantly associated with post-operative neck pain attenuation still remain unclear. The primary aim of the present study was to determine factors significantly associated with post-operative neck pain attenuation in patients with cervical OPLL using a prospective multi-centre registry of surgically treated cervical OPLL. Significant postoperative neck pain reduction (50% reduction of neck pain) was achieved in 31.3% of patients. There was no significant difference in neck pain attenuation between surgical procedures. Statistical analyses with univariate analyses followed by stepwise logistic regression revealed neurological recovery as a factor having a significant positive association with post-operative neck pain attenuation (p = 0.04, odds ratio 5.68 (95% confidence interval: 1.27–22.2)). In conclusion, neurological recovery was an independent factor having a significant positive association with post-operative neck pain attenuation in patients with cervical myelopathy caused by OPLL who underwent cervical spine surgery.

Low cut-off of FIB-4 is a widely used formula to exclude advanced liver fibrosis in primary care centers. However, the range of reported threshold of FIB-4 to rule in advanced fibrosis is too broad across etiologies, and no consensus has been reached. In the present study, we investigated the role of FIB-4 for a reassessment of hepatic fibrosis burden in a referral center. We compared the diagnostic performance of FIB-4 among patients with liver disease of various causes and tried to find an optimal cut-off value for predicting advanced fibrosis. Among 1068 patients, the AUROC of FIB-4 to diagnose advanced fibrosis showed no significant difference among the various etiologies of liver disease, ranging from 0.783 to 0.821. The optimal cut-off value obtained by maximizing Youden's index was 2.68, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for predicting advanced fibrosis were 70.7%, 79.1%, 43.5%, and 92.2%, respectively. The PPV was low in patients with autoimmune disease (6.67%). When we incorporated the new cut-off of FIB-4 into abdominal ultrasound findings, 81% of unnecessary work-ups would be appropriately avoided. In conclusion, the cut-off value of 2.68 showed an acceptable PPV while maintaining a high NPV to predict advanced fibrosis, most etiology except for autoimmune diseases. This result could assist in establishing an appropriate timing to reassess the hepatic fibrosis burden during monitoring in the referral center.

This study analyzes the relationship between contrast-sensitivity and higher-order aberrations (HOA) in mild and subclinical-keratoconus in subjects with good visual-acuity (VA). Keratoconus group (including subclinical-keratoconus) and controls underwent autokeratometry, corneal-tomography, autorefraction and HOA measurement. Contrast-sensitivity was tested using a psychophysical two-alternative forced-choice Gabor patches in three blocks (6, 9, 12 cycles/deg). Controls were compared to the keratoconus group and to a keratoconus subgroup with VA of 0.00 LogMar group ("keratoconus-0.00VA"). Spearman correlation tested association between HOA and contrast-sensitivity. Twenty-two keratoconus subjects (38 eyes: 28 keratoconus, 10 subclinical-keratoconus, 20 keratoconus-0.00VA) and 35 controls were included. There was a significant difference between control and keratoconus, and between control and keratoconus-0.00VA, for keratometry, cylinder, thinnest and central corneal thickness (p

Air injection is an accessory technique during scleral buckling (SB). Subclinical subretinal fluid (SRF) may presence and persistent after SB. The impact of air injection on SRF is unclear. In the study, we retrospectively enrolled 51 patients with macular-involving RD who had undergone successful SB. They were categorized into Group A (SB without air injection) and Group B (SB with air injection). First, we found that although group B seem to be severer than group A before surgery, Kaplan–Meier graph showed that SRF absorbed more rapidly in group B after surgery, and the incidence of SRF in group B was much lower during the whole follow-up period. Moreover, the cases with superior breaks had the lowest incidence. Second, during the follow-up period, there was no significant difference about postoperative complication between two groups. Lastly, risk factors for persistent SRF were investigated with binary logistic regression, and no risk factor was found. In conclusion, air injection during the SB might accelerate SRF absorption and reduce the incidence of persistent SRF, especially for the longstanding macular-off RD with superior breaks.

The presence of magnetic nanoparticles (MNPs) in the human brain was attributed until recently to endogenous formation; associated with a putative navigational sense, or with pathological mishandling of brain iron within senile plaques. Conversely, an exogenous, high-temperature source of brain MNPs has been newly identified, based on their variable sizes/concentrations, rounded shapes/surface crystallites, and co-association with non-physiological metals (e.g., platinum, cobalt). Here, we examined the concentration and regional distribution of brain magnetite/maghemite, by magnetic remanence measurements of 147 samples of fresh/frozen tissues, from Alzheimer’s disease (AD) and pathologically-unremarkable brains (80–98 years at death) from the Manchester Brain Bank (MBB), UK. The magnetite/maghemite concentrations varied between individual cases, and different brain regions, with no significant difference between the AD and non-AD cases. Similarly, all the elderly MBB brains contain varying concentrations of non-physiological metals (e.g. lead, cerium), suggesting universal incursion of environmentally-sourced particles, likely across the geriatric blood–brain barrier (BBB). Cerebellar Manchester samples contained significantly lower (~ 9×) ferrimagnetic content compared with those from a young (29 years ave.), neurologically-damaged Mexico City cohort. Investigation of younger, variably-exposed cohorts, prior to loss of BBB integrity, seems essential to understand early brain impacts of exposure to exogenous magnetite/maghemite and other metal-rich pollution particles.

Steroids are often utilized to manage patients with non-small cell lung cancer brain metastases (NSCLCBM). Steroids and elevated neutrophil-to-lymphocyte ratio (NLR) have been associated with decreased overall survival (OS) in patients treated with immune checkpoint inhibitors (ICI). We retrospectively investigated patients treated with ICI after the diagnosis of NSCLCBM at a single tertiary care institution examing the impact of steroids and NLR. Overall survival (OS) and intracranial progression-free survival (PFS) were analyzed. 171 patients treated with ICI for NSCLCBM were included. Thirty-six received steroids within 30 days of the start of ICI, and 53 patients had an NLR ≥ 5 before the start of ICI. Upfront steroids was associated with decreased OS on multivariable analysis (median OS 10.5 vs. 17.9 months, p = .03) and intracranial PFS (5.0 vs. 8.7 months, p = .045). NLR ≥ 5 was indicative of worse OS (10.5 vs. 18.4 months, p = .04) but not intracranial PFS (7.2 vs. 7.7 months, p = .61). When NLR and upfront steroids are modeled together, there is a strong interaction (p = .0008) indicating that the impact of steroids depended on the patient’s NLR. In a subgroup analysis, only in patients with NLR p = .032). The impact of steroids on the efficacy of ICI in patients with NSCLCBM is dependent on the patient's NLR underscoring its importance in these patients. Patients with a low NLR, steroid use decreases the efficacy of ICI. These results can inform clinicians about the impact of steroids in patients treated with ICI.

The study aimed to assess the safety of one-stage bilateral total hip arthroplasty (THA) compared with unilateral THA. In this retrospective observational case–control study were included patients undergoing unilateral (group 1) and one-stage bilateral (group 2) THA in a high-volume center. The groups were matched for gender, age at surgery, and pre-operative American Society of Anesthesiology score. The following variables were assessed: local and systemic complications, postoperative anemia, 30-day and 1-year readmission and reoperation rates, length of hospital stay, and ambulation time. Group 1 reported a significantly higher rate of local and systemic complications compared with group 2 (5.4% versus 3.9% and 29.6% versus 4.7%, respectively). Postoperative anemia was significantly lower in group 1 compared with group 2 (8.1% versus 30%). There was no significant difference in terms of 30-day and 1-year readmission rates between the two groups. The average length of hospital stay was 5.1 ± 2.3 days in group 1, and 5.3 ± 1.9 days in group 2 (p = 0.78). Ambulation time was significantly lower for group 1 (day 0.9 ± 0.9 in group 1, and day 1 ± 0.8 in group 2, p = 0.03). In a high-volume center, one-stage bilateral THA is a safe procedure compared with unilateral THA in terms of postoperative local and systemic complications, 30-day readmission and 1-year reoperation rates, and length of hospital stay.

Patients afflicted with melanoma show lower vitamin D serum levels (VDSL) than the healthy population. This hypothesis agrees with its well-known antiproliferative features. An observational study was carried out to collect VDSL in patients suffering from melanoma. Our aim was to identify a potential connection between low VDSL and the risk to incur melanoma. Furthermore, we studied the association between VDSL at the diagnosis of melanoma and other germane prognostic factors. The population held in regard was composed of 154 patients with a diagnosis of melanoma between 2016 and 2019. These patients were retrospectively collected from our follow-up storage. We compared VDSL to clinical and pathological parameters (age, sex, tumour location, Breslow’s depth, Clark’s level, histological subtype, ulceration, et aliqua). Moreover, we recruited a control group with negative melanoma history. Mean and median of VDSL were significantly lower in the melanoma group. Instead, we found a negative association between melanoma and VDSL > 30 ng/L (OR 0.11; p thin (depth ≤ 1 mm) and thick tumours (depth > 1 mm) revealed a statistically significant difference (21.1 ± 8.2 ng/L vs 17.8 ± 8.1; p = 0.01). Moreover, VDSL were significantly lower in melanomas with mitotic rate ≥ 1/mm2 (22.1 ± 8.3 ng/L; p p = 0.76; p = 0.74). Besides, our study revealed no association between VDSL and histological subtype (p = 0.161). Lower VDSL correlate with thick and high mitotic rate tumours. Future prospective studies would investigate if appropriate upkeep of suitable VDSL can decrease the risk of primary and recurrent melanoma diagnosis.

In this work, we sought to delineate the prevalence of cardiothoracic imaging findings of Proteus syndrome in a large cohort at our institution. Of 53 individuals with a confirmed diagnosis of Proteus syndrome at our institution from 10/2001 to 10/2019, 38 individuals (men, n = 23; average age = 24 years) underwent cardiothoracic imaging (routine chest CT, CT pulmonary angiography and/or cardiac MRI). All studies were retrospectively and independently reviewed by two fellowship-trained cardiothoracic readers. Disagreements were resolved by consensus. Differences between variables were analyzed via parametric and nonparametric tests based on the normality of the distribution. The cardiothoracic findings of Proteus syndrome were diverse, but several were much more common and included: scoliosis from bony overgrowth (94%), pulmonary venous dilation (62%), band-like areas of lung scarring (56%), and hyperlucent lung parenchyma (50%). In addition, of 20 individuals who underwent cardiac MRI, 9/20 (45%) had intramyocardial fat, mostly involving the endocardial surface of the left ventricular septal wall. There was no statistically significant difference among the functional cardiac parameters between individuals with and without intramyocardial fat. Only one individual with intramyocardial fat had mildly decreased function (LVEF = 53%), while all others had normal ejection fraction.

While phrenic nerve palsy (PNP) due to cryoballoon pulmonary vein isolation (PVI) of atrial fibrillation (AF) was transient in most cases, no studies have reported the results of the long-term follow-up of PNP. This study aimed to summarize details and the results of long-term follow-up of PNP after cryoballoon ablation. A total of 511 consecutive AF patients who underwent cryoballoon ablation was included. During right-side PVI, the diaphragmatic compound motor action potential (CMAP) was reduced in 46 (9.0%) patients and PNP occurred in 29 (5.7%) patients (during right-superior PVI in 20 patients and right-inferior PVI in 9 patients). PNP occurred despite the absence of CMAP reduction in 0.6%. The PV anatomy, freezing parameters and the operator’s proficiency were not predictors of PNP. While PNP during RSPVI persisted more than 4 years in 3 (0.6%) patients, all PNP occurred during RIPVI recovered until one year after the ablation. However, there was no significant difference in the recovery duration from PNP between PNP during RSPVI and RIPVI. PNP occurred during cryoballoon ablation in 5.7%. While most patients recovered from PNP within one year after the ablation, PNP during RSPVI persisted more than 4 years in 0.6% of patients.

The purpose of this work is to evaluate the performance of applying patient dosimetric information induced by individual uniform-intensity radiation fields in organ-at risk (OAR) dose-volume histogram (DVH) prediction, and extend to DVH prediction of planning target volume (PTV). Ninety nasopharyngeal cancer intensity-modulated radiation therapy (IMRT) plans and 60 rectal cancer volumetric modulated arc therapy (VMAT) plans were employed in this study. Of these, 20 nasopharyngeal cancer cases and 15 rectal cancer cases were randomly selected as the testing data. The DVH prediction was performed using two methods. One method applied the individual dose-volume histograms (IDVHs) induced by a series of fields with uniform-intensity irradiation and the other method applied the distance-to-target histogram and the conformal-plan-dose-volume histogram (DTH + CPDVH). The determination coefficient R2 and mean absolute error (MAE) were used to evaluate DVH prediction accuracy. The PTV DVH prediction was performed using the IDVHs. The PTV dose coverage was evaluated using D98, D95, D1 and uniformity index (UI). The OAR dose was compared using the maximum dose, V30 and V40. The significance of the results was examined with the Wilcoxon signed rank test. For PTV DVH prediction using IDVHs, the clinical plan and IDVHs prediction method achieved mean UI values of 1.07 and 1.06 for nasopharyngeal cancer, and 1.04 and 1.05 for rectal cancer, respectively. No significant difference was found between the clinical plan results and predicted results using the IDVHs method in achieving PTV dose coverage (D98,D95,D1 and UI) for both nasopharyngeal cancer and rectal cancer (p-values ≥ 0.052). For OAR DVH prediction, no significant difference was found between the IDVHs and DTH + CPDVH methods for the R2, MAE, the maximum dose, V30 and V40 (p-values ≥ 0.087 for all OARs). This work evaluates the performance of dosimetric information of several individual fields with uniform-intensity radiation for DVH prediction, and extends its application to PTV DVH prediction. The results indicated that the IDVHs method is comparable to the DTH + CPDVH method in accurately predicting the OAR DVH. The IDVHs method quantified the input features of the PTV and showed reliable PTV DVH prediction, which is helpful for plan quality evaluation and plan generation.

Play behaviour and tool using in birds, two well-delineated and amply researched behaviours, have generally been associated with cognitive abilities. In this study, these behaviours were related to relative brain mass in a sample of Australian native birds. Despite suggestive research results so far between cognition and tool using, this study found no significant difference in relative brain mass or in lifespan between tool-using birds and non-tool users. By contrast, in play behaviour, subdivided into social players and non-social players, the results showed statistically very clear differences in relative brain mass between social, non-social and non-players. Social play was associated with both the largest brain mass to body mass ratios and with the longest lifespans. The results show that play behaviour is a crucial variable associated with brain enlargement, not tool using. Since many of the tool using species tested so far also play, this study suggests that false conclusions can be drawn about the connection between tool using and cognitive ability when the silent variable (play behaviour) is not taken into account.

Previous studies have suggested excess GH/IGF1 secretion in patients with acromegaly is protective for periodontal health. Diabetes is prevalent comorbidity in patients of acromegaly and is associated with worsening of periodontal disease. The present study evaluates the periodontal health and cytokines status in treatment-naive active acromegaly patients with and without diabetes. Eleven patients, each of acromegaly with and without diabetes and 20 healthy controls were enrolled. Periodontal parameters were assessed. GCF and blood samples for IL-6, TGF-β1, and PDGF were obtained. Serum GH, IGF1, HbA1c, pituitary hormones and MRI sella were performed in patients with acromegaly. There was no significant difference in periodontal status of patients with acromegaly and healthy controls. However, a significant increase in serum IL-6 (p = 0.019) and TGF-β1 (p = 0.025) levels in patients with acromegaly was observed and all patients had concurrent hypogonadism. Nevertheless, the patients with acromegaly having diabetes had modestly higher CAL and PD and serum IL-6 levels (p = 0.051), but it could not exert adverse effects on periodontal health in presence of GH/IGF1 excess. GH/IGF1 excess did not exert a protective effect on periodontal status in acromegaly, possibly due to concurrent hypogonadism and opposing cytokines; however, it could mask the ill-effects of diabetes on periodontal health.

Preoperative immune-nutritional status is correlated with postoperative outcomes. The Controlling Nutritional Status (CONUT) score is a useful tool for predicting the postoperative outcomes of cancer surgery. This study aimed to evaluate whether the CONUT score could predict postoperative complications in Crohn’s disease (CD) patients. In total, 202 CD patients were eligible. Univariate and multivariate analyses were performed to identify risk factors for postoperative complications. Receiver operating characteristic (ROC) curves were generated to examine the cutoff value for predictors of postoperative complications. Among all the patients, 66 developed postoperative complications. The cut-off value of the CONUT score was 3.5 for complications. Eighty-one patients had a low CONUT score ( 3.5). There was a significant difference in postoperative complications between the groups with low and high CONUT score (17.3% vs. 43.0%, p

This study aimed to assess the validity and functional relevance of a standardized procedure to assess lower limb muscle power by means of the 30-s sit-to-stand (STS) test when compared to leg extension power (LEP), traditional STS performance and handgrip strength. A total of 628 community-dwelling older subjects (60–93 years) from the Copenhagen Sarcopenia Study were included. Physical performance was assessed by the 30-s STS and 10-m maximal gait speed tests. Handgrip strength and LEP were recorded by a hand-held dynamometer and the Nottingham power rig, respectively. STS muscle power was calculated using the subjects’ body mass and height, chair height and the number of repetitions completed in the 30-s STS test. We found a small albeit significant difference between LEP and unilateral STS power in older men (245.5 ± 88.8 vs. 223.4 ± 81.4 W; ES = 0.26; p p > 0.05). Notably, a large positive correlation was observed between both measures (r = 0.75; p vs 0.35–0.45; p

To test our hypothesis that the magnitude of reduction in hsCRP achieved by antihypertensive medications may predict the benefit for cardiovascular outcomes in hypertensive individuals, we performed subanalysis of the ATTEMPT-CVD study. The hypertensive participants enrolled in the ATTMEPT-CVD study were categorized into two groups according to whether achieved reduction in hsCRP levels at 6 months after initiation of antihypertensive medications from baseline was equal to or greater than 40% (responder group) or less than 40% (non-responder group). Baseline characteristics and blood pressure during follow-up period were similar between the groups. For women, the incidence of cardiovascular events was significantly less in responder group than non-responder group (P This trial was registered with ClinicalTrials.gov, number NCT01075698.

Cryopreservation is a well-established method for bone storage. However, the ideal timing of mechanical testing after sacrificing the experimental animals is still under discussion and of significant importance to the presentation of accurate results. Therefore, the aim of this study was to investigate and compare different cryopreservation durations to native murine bone and whether there was an influence on mechanical bone testing. For this study the tibias of 57 female C57BL/6 mice—18-weeks of age—were harvested and randomly allocated to one of four groups with varying storage times: (1) frozen at −80 °C for 3 months, (2) frozen at −80 °C for 6 months, (3) frozen at −80 °C for 12 months and (4) native group. The native group was immediately tested after harvesting. The comparison of the mean strength and load to failure rates demonstrated a significant difference between the storage groups compared to the native control (p = 0.007). However, there was no difference in the strength and the load to failure values of bones of all storage groups when compared against each other. Once cryopreservation at −80 °C is performed, no differences of mechanical bone properties are seen up to 12 months of storage. When actual in vivo data is of close interest, immediate testing should be considered and is preferred. If comparison of groups is required and long-time storage is necessary, cryopreservation seems to be an accurate method at present.

Inherited retinal dystrophy (IRD) patients often experience photophobia. However, its mechanism has not been elucidated. This study aimed to investigate the main wavelength of light causing photophobia in IRD and difference among patients with different phenotypes. Forty-seven retinitis pigmentosa (RP) and 22 cone-rod dystrophy (CRD) patients were prospectively recruited. We designed two tinted glasses: short wavelength filtering (SWF) glasses and middle wavelength filtering (MWF) glasses. We classified photophobia into three types: (A) white out, (B) bright glare, and (C) ocular pain. Patients were asked to assign scores between one (not at all) and five (totally applicable) for each symptom with and without glasses. In patients with RP, photophobia was better relieved with SWF glasses {“white out” (p

Molecular investigations are crucial for further developments in precision medicine. RNA sequencing, alone or in combination with further omic-analyses, resulted in new therapeutic strategies. In this context, biobanks represent infrastructures to store tissue samples and body fluids in combination with clinical data to promote research for new predictive and prognostic biomarkers as well as therapeutic candidate molecules. Until today, the optimal storage conditions are a matter of debate especially with view to the storage temperature. In this unique approach we compared parallel samples from the same tumour, one half stored at − 80 °C and one half in the vapor phase of liquid nitrogen, with almost identical pre-analytical conditions. We demonstrated that RNA isolated from breast cancer samples revealed significantly higher RINe-values after 10 years of storage in the vapor phase of liquid nitrogen compared to storage at − 80 °C. In contrast, no significant difference was found regarding the DIN-values after DNA isolation. Morphological changes of the nucleus and cytoplasm, especially in the samples stored at − 80 °C, gave insights to degenerative effects, most possibly due to the storage protocol and its respective peculiarities. In addition, our results indicate that exact point-to point documentation beginning at the sample preparation is mandatory.

Goal-directed decision making often requires evaluating the outcomes of our decisions, assessing any gains or losses, learning from performance-related feedback, and deciding whether to alter our future decisions. However, it is unclear how these processes can be influenced by the saliency of an outcome (e.g., when one aspect of the outcome is accentuated more than another). Here we investigated whether decision strategies changed when certain aspects of the task outcome (win/loss or correct/incorrect) became more salient and how our brain encoded such saliency signals. We employed a simple two-alternative forced choice gambling task and quantified the frequency at which participants switched decisions to an alternative option in the subsequent trial after receiving feedback on their current selection. We conducted three experiments. In Experiment 1, we established the baseline decision switching behavior: participants switched more frequently following incorrect trials than correct trials, but there was no significant difference between win and loss trials. In Experiment 2, we highlighted the utility (win or loss) or performance (correct or incorrect) dimension of the chosen outcome and we found that the difference in switching frequency was enlarged along the highlighted dimension. However, Experiment 3 showed that when using non-specific saliency emphasis of the outcome, the saliency effect was abolished. We further conducted simultaneous EEG recordings using specific saliency emphasis and found that the feedback-related negativity, P300, and late positive potential could collectively encode saliency modulation of behavioral switching. Lastly, both the frontal and parietal theta-band power encoded the outcome when it was made more salient. Together, our findings suggest that specific outcome saliency can modulate behavioral decision switching between choices and our results have further revealed the neural signatures underlying such saliency modulation. Altering the saliency of an outcome may change how information is weighed during outcome evaluation and thus influence future decisions.

Computed tomography imaging plays a major role in the preoperative assessment of tumor burden by providing an accurate mapping of the distribution of peritoneal metastases (PM). Spectral Photon Counting Computed Tomography (SPCCT) is an innovative imaging modality that could overcome the current limitations of conventional CT, offering not only better spatial resolution but also better contrast resolution by allowing the discrimination of multiple contrast agents. Based on this capability, we tested the feasibility of SPCCT in the detection of PM at different time of tumor growth in 16 rats inoculated with CC531 cells using dual-contrast injection protocols in two compartments (i.e. intravenous iodine and intraperitoneal gadolinium or the reverse protocol), compared to surgery. For all peritoneal regions and for both protocols, sensitivity was 69%, specificity was 100% and accuracy was 80%, and the correlation with surgical exploration was strong (p = 0.97; p = 0.0001). No significant difference was found in terms of diagnostic performance, quality of peritoneal opacification or diagnostic quality between the 2 injection protocols. We also showed poor vascularization of peritoneal metastases by measuring low concentrations of contrast agent in the largest lesions using SPCCT, which was confirmed by immunohistochemical analyses. In conclusion, SPCCT using dual-contrast agent injection protocols in 2 compartments is a promising imaging modality to assess the extent of PM in a rat model.

The aim of this study was to investigate the value of multiple parameters retrieved from the FDG PET/CT studies, including SUVmax, SUVmean, SUVpeak, MTV, TLG, tumour size in differentiating retroperitoneal paragangliomas from UCD. 28 patients with solitary retroperitoneal masses who had undergone preoperative 18F-FDG PET/CT were retrospectively evaluated. Histopathology by surgical resection confirmed 17 paragangliomas and 11 UCDs. SUVmax, SUVmean, SUVpeak, MTV, TLG, and tumour size of 18F-FDG PET/CT were measured for each patient. Mann–Whitney U-test was used to assess differences in multiple parameters between paragangliomas and UCDs. The ROC curve analysis was performed to determine the differential diagnostic value of these parameters. Paragangliomas presented significantly higher SUVmax (P P = 0.001), SUVpeak (P P = 0.024) than UCDs, whereas no significant difference was observed in MTV. The AUCs for differentiating paragangliomas and UCDs were 0.920, 0.888, 0.909, and 0.765 for SUVmax, SUVmean, SUVpeak, and TLG, respectively. The SUVmax cut-off of 7.75 yielded 82.4% sensitivity and 100% specificity for predicting paragangliomas. This study indicated that 18F FDG PET/CT-derived multiple metabolic parameters are useful in distinguishing between paragangliomas and UCDs. SUVmax showed the best result for the differential diagnosis of these two diseases among multiple metabolic parameters.

There are few studies assessing pre-hypertension and an impaired fasting glucose (IFG) and their combined effects on the cancer risk. We investigated the impact of pre-hypertension on cancer risk and IFG, and their combined effects on the cancer risk. This study included 371,762 subjects (≥40 years) who had never been diagnosed with hypertension, diabetes mellitus (DM), and cancer before. During a mean follow-up of 10.06 ± 1.86 years, 35,605 (9.58%) of the subjects developed cancer. In men only, cancer risk was significantly increased with an increase in the blood pressure (BP) (P for trend

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease leading to progressive and irreversible muscle atrophy. The diagnosis of ALS is time-consuming and complex, with the clinical and neurophysiological evaluation accompanied by monitoring of progression and a long procedure for the discrimination of similar neurodegenerative diseases. The delayed diagnosis strongly slows the potential development of adequate therapies and the time frame for a prompt intervention. The discovery of new biomarkers could improve the disease diagnosis, as well as the therapeutic and rehabilitative effectiveness and monitoring of the pathological progression. In this work saliva collected from 19 patients with ALS, 10 affected by Parkinson’s disease, 10 affected by Alzheimer’s disease and 10 healthy subjects, was analysed using Raman spectroscopy, optimizing the parameters for detailed and reproducible spectra. The statistical multivariate analysis of the data revealed a significant difference between the groups, allowing the discrimination of the disease onset. Correlation of Raman data revealed a direct relationship with paraclinical scores, identifying multifactorial biochemical modifications related to the pathology. The proposed approach showed a promising accuracy in ALS onset discrimination, using a fast and sensitive procedure that can make more efficient the diagnostic procedure and the monitoring of therapeutic and rehabilitative processes in ALS.

Background: Incidental findings are a well-known complication of imaging studies done for both diagnostic and research purposes. Little is known about the rates and types of incidental findings found on brain MRI in patients with HIV infection, who may be at risk for HIV-Associated Neurocognitive Disorders (HAND). Methods: The parent study included 108 adults with HIV infection and 125 demographically-matched uninfected controls who completed MRI and neuropsychological testing. Incidental findings were classified by the study team as vascular, neoplastic, congenital, other neurologic, or non-neurologic. Categorical measures were compared using Pearson chi-square tests; continuous measures were compared using t-tests. Results: Among participants with HIV infection, 36/108 (33%) had incidental findings compared to 33/125 (26%) controls (p = 0.248). Rates of incidental findings were significantly correlated with increasing age in both participants with HIV infection (p = 0.013) and controls (p = 0.022). We found no correlation between presence of incidental findings and sex or race/ethnicity among either cohort, and no correlation with CD4 count or HAND status for the HIV-infected cohort. Conclusions: Incidental findings were common in both participants with HIV infection and controls, at higher rates than previously reported in healthy populations. There was no significant difference in prevalence between the groups.

The aim of this study was to establish a feasible and robust magnetic resonance imaging protocol for the quantitative assessment of cardiac function in marmosets and to present normal values of cardiac function across different ages from young adult, middle-aged, to very old clinically healthy animals. Cardiac MRI of 33 anesthetized marmosets at the age of 2–15 years was performed at 9.4 T using IntraGate-FLASH that operates without any ECG-triggering and breath holding. Normalized to post-mortem heart weight, the left ventricular end-diastolic volume (LV-EDV) was significantly reduced in older marmosets. The LV end-systolic volume (LV-ESV) and the LV stroke volume (LV-SV) showed a similar trend while the LV ejection fraction (LV-EF) and wall thickening remained unchanged. Similar observations were made for the right ventricle. Moreover, the total ventricular myocardial volume was lower in older monkeys while no significant difference in heart weight was found. In conclusion, IntraGate-FLASH allowed for quantification of left ventricular cardiac function but seems to underestimate the volumes of the right ventricle. Although less strong and without significant sex differences, the observed age related changes were similar to previously reported findings in humans supporting marmosets as a model system for age related cardiovascular human diseases.

In external radiotherapy (RT), the use of flattening filter-free (FFF) radiation beams obtained by removing the flattening filter (FF) in standard linear accelerators is rapidly increasing, and the benefits of clinical use are the issue of research. Advanced treatment techniques have increased the interest in the operation of linear accelerators in FFF mode. The differences of the beams with non-uniform dose distribution created by removing FF compared to the beams with uniform dose distribution used as a standard were examined. These differences were compared in the treatment plans of lung patients who have different planning target volumes (PTV). Clinac IX linear accelerator units were used. Twenty patients with previously completed treatment were divided into two groups depending on the size of the target volume. All patients underwent two different intensity-modulated RT (IMRT) plans using FF and FFF beams. The Wilcoxon Signed-Rank test was used to compare two different techniques (Significance p

Among patients with cervical myelopathy who were diagnosed with neuropathic pain (NP) by the LANSS test, the study participants were randomly assigned to one of the two study groups. The participants in one study group received opioids only, while those in the other group received opioids and pregabalin. Thirty-nine patients were analyzed in the study (20 patients in the opioid-only group and 19 in the pregabalin add-on group). The LANSS, neck pain, and arm pain scores in the pregabalin add-on group improved significantly compared with those in the opioid-only group after the first 4 weeks (p = 0.005, 0.001 and 0.035, respectively), but there was no significant difference between the two groups during the next 4 weeks (p = 0.615, 0.377 and 0.716, respectively). There was no significant difference in the neck disability index and EuroQol-5Dimension scores after four weeks and eight weeks of follow-up. Adverse events were reported by four patients (20.0%) in the opioid-only group and five patients (26.3%) in the pregabalin add-on group (p = 0.716). However, over time, the occurrence of side effects and dropouts increased in the pregabalin add-on group. This exploratory pilot study suggests that pregabalin add-on treatment is more efficient than the use of opioids alone at the beginning of NP treatment in cervical myelopathy patients. However, prescribing pregabalin add-on treatment for more than four weeks should be done cautiously.

Lipedema is a chronic, progressive disease of adipose tissue with lack of consistent diagnostic criteria. The aim of this study was a thorough comparative characterization of extracellular microRNAs (miRNAs) from the stromal vascular fraction (SVF) of healthy and lipedema adipose tissue. For this, we analyzed 187 extracellular miRNAs in concentrated conditioned medium (cCM) and specifically in small extracellular vesicles (sEVs) enriched thereof by size exclusion chromatography. No significant difference in median particle size and concentration was observed between sEV fractions in healthy and lipedema. We found the majority of miRNAs located predominantly in cCM compared to sEV enriched fraction. Surprisingly, hierarchical clustering of the most variant miRNAs showed that only sEVmiRNA profiles – but not cCMmiRNAs – were impacted by lipedema. Seven sEVmiRNAs (miR–16-5p, miR-29a-3p, miR-24-3p, miR-454-p, miR–144-5p, miR-130a-3p, let-7c-5p) were differently regulated in lipedema and healthy individuals, whereas only one cCMmiRNA (miR-188-5p) was significantly downregulated in lipedema. Comparing SVF from healthy and lipedema patients, we identified sEVs as the lipedema relevant miRNA fraction. This study contributes to identify the potential role of SVF secreted miRNAs in lipedema.

When considering the “beauty-is-good” stereotype, facial attractiveness should facilitate empathy for pain. On the other hand, having in mind the “threat value of pain” hypothesis, pain cues would be more salient, and thus, its processing would not suffer influence by facial attractiveness. The event-related potential (ERP) allows investigating if one of these theories could predict individuals’ responses regarding the perception of pain or attractiveness in others’ faces. We tracked 35 participants’ reactions to pictures depicting more and less attractive faces displayed in a painful and non-painful condition. Each participant completed the following two tasks when presented the images of faces: (1) the Pain Judgment Task, in which participants should rate the pain levels, and (2) the Attractiveness Judgment Task, in which participants should rate the attractiveness. Results showed that participants exhibited differences rating more and less attractive faces in the non-painful pictures, but not in the painful pictures. These results were observed in P3 and LPC amplitudes in the Pain Judgment Task, as well as in N170 and P2 amplitudes in the Attractive Judgment Task. Our results suggested that both explicit and implicit empathic pain processing inhibited the processing of attractiveness perception. These findings supported the “threat value of pain” hypothesis. Besides, in the Attractive Judgment Task, the N170 and P2 amplitudes for more attractive painful pictures were larger than those for more attractive non-painful pictures. In contrast, no significant difference was found between the amplitudes for painful and non-painful, less attractive pictures. Our findings suggest that explicit facial attractiveness processing for more attractive face images potentiates the implicit empathy for pain processing, therefore partly supporting the “beautiful-is-good” stereotype.

To describe the perinatal outcomes of twin pregnancies with preterm premature rupture of membranes (PPROM) before 34 weeks’ gestation and identify factors associated with discharge without severe or moderate-severe neonatal morbidity. This study was conducted as a retrospective analysis of twin pregnancies with PPROM occurring at 24 0/7 to 33 6/7 weeks’ gestation. Perinatal outcomes were assessed by gestational age (GA) at PPROM and compared between PPROM and non PPROM twins. Factors associated with discharge without severe or moderate-severe neonatal morbidity were identified using logistic regression analysis. Of the 180 pregnancies (360 foetuses), only 17 (9.4%) women remained pregnant 7 days after PPROM. There were 10 (2.8%) cases of prenatal or neonatal death; 303 (84.2%) and 177 (49.2%) neonates were discharged without severe or moderate-severe morbidity, respectively. As GA at PPROM increased, the adverse obstetric and neonatal outcomes decreased, especially after 32 weeks. There was no significant difference in general neonatal outcomes between PPROM and non PPROM twins. The GA at PPROM and latency period were both significantly associated with discharge without severe or moderate-severe neonatal morbidity. Pregnancy complications and 5-min Apgar score

Radiotherapy requires the target area and the organs at risk to be contoured on the CT image of the patient. During the process of organs-at-Risk (OAR) of the chest and abdomen, the doctor needs to contour at each CT image. The delineations of large and varied shapes are time-consuming and laborious. This study aims to evaluate the results of two automatic contouring softwares on OARs definition of CT images of lung cancer and rectal cancer patients. The CT images of 15 patients with rectal cancer and 15 patients with lung cancer were selected separately, and the organs at risk were manually contoured by experienced physicians as reference structures. And then the same datasets were automatically contoured based on AiContour (version 3.1.8.0, Manufactured by Linking MED, Beijing, China) and Raystation (version 4.7.5.4, Manufactured by Raysearch, Stockholm, Sweden) respectively. Deep learning auto-segmentations and Atlas were respectively performed with AiContour and Raystation. Overlap index (OI), Dice similarity index (DSC) and Volume difference (Dv) were evaluated based on the auto-contours, and independent-sample t-test analysis is applied to the results. The results of deep learning auto-segmentations on OI and DSC were better than that of Atlas with statistical difference. There was no significant difference in Dv between the results of two software. With deep learning auto-segmentations, auto-contouring results of most organs in the chest and abdomen are good, and with slight modification, it can meet the clinical requirements for planning. With Atlas, auto-contouring results in most OAR is not as good as deep learning auto-segmentations, and only the auto-contouring results of some organs can be used clinically after modification.

Yogurt quality mainly depends on nutritional properties, microbial diversity and purity of starter culture. This study aimed to assess the nutritional composition and microbiome diversity in yogurt. Microbial diversity was analyzed by 16S and 18S rRNA based high-throughput sequencing. Significantly (Ppermanova=0.001) and fungal (Ppermanova=0.013) diversity between sweet and sour yogurt was recorded. We detected 76 bacterial and 70 fungal genera across these samples which were mostly represented by Firmicutes (>92%) and Ascomycota (98%) phyla, respectively. Among the detected genera, 36.84% bacterial and 22.86% fungal genera were found in both yogurt types. Our results suggest that Streptococcus (50.82%), Lactobacillus (39.92%), Enterobacter (4.85%), Lactococcus (2.84%) and Aeromonas (0.65%) are the most abundant bacterial genera, while Kluyveromyces (65.75%), Trichosporon (8.21%), Clavispora (7.19%), Candida (6.71%), Iodophanus (2.22%), Apiotrichum (1.94%), and Issatchenkia (1.35%) are the most abundant fungal genera in yogurt metagenomes. This is the first study on nutritional properties and microbiome diversity of Bangladeshi yogurt that would be a benchmark for safe production of quality yogurt by commercial manufacturers.

There is no recognized serum biomarker to predict the recurrence of endometrial carcinoma (EC). We aimed to explore serum human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) as the biomarkers to predict and monitor recurrence of type II EC. 191 patients diagnosed with type II EC were involved for this retrospective study. Comparing recurrent with non-recurrent patients, HE4 levels resulted a statistically significant difference at primary diagnosis and recurrence, respectively (P = 0.002 and P =