Diaphragmatic paralysis: a complication of lung transplantation.
Damage to the phrenic nerve, either unilaterally or bilaterally, is a well-documented complication of cardiac operation, but less commonly reported after lung transplantation. A retrospective review of 185 single and sequential single lung transplant procedures was performed at The Toronto Hospital. Objective confirmation (fluoroscopy or ultrasound) of diaphragmatic paralysis was found in 6 patients. Paralysis was unilateral in 5 patients (all were left sided) and bilateral in 1 patient. The average length of ventilation was 8.2 +/- 9.2 days with an average intensive care unit stay of 11.2 +/- 10.6 days. Mean duration in the hospital was 37.5 +/- 11.1 days. The average length of intensive care unit stay and hospitalization were compared with all other sequential single transplantations performed from approximately the time of the first documented case of diaphragmatic paralysis. Intensive care unit stay and hospitalization for the other (no diaphragmatic paralysis) transplant recipients were significantly shorter (5.3 +/- 2.7 and 29.1 +/- 12.9 days, respectively; p < 0.05). One patient required noninvasive ventilatory assistance via bilevel positive airway pressure in the hospital. One other patient used bilevel positive airway pressure in the hospital and overnight for 6 months after discharge. All patients obtained acceptable lung function and were ambulatory upon discharge from the hospital. Clinically detectable diaphragmatic paralysis is an infrequent complication of lung transplantation and is associated with longer intensive care unit stay and hospitalization, but is not associated with significant adverse outcomes.


Movement of the ribs in supine humans for small and large changes in lung volume.
An object-tracking algorithm was used on computed tomography (CT) images of the thorax from six healthy participants and nine participants with chronic obstructive pulmonary disease (COPD) to describe the movement of the ribs between the static lung volumes of functional residual capacity (FRC) and total lung capacity (TLC). The continuous motion of the ribs during tidal breathing was also described using four-dimensional CT datasets from seven participants with thoracic esophageal malignancies. Rib motion was defined relative to a local joint coordinate system where rotations about the axes that predominantly affected the anteroposterior and transverse diameters of the rib cage were referred to as pump-handle and bucket-handle movements, respectively. Between TLC and FRC, pump-handle movements were 1.8 times larger in healthy participants than in participants with COPD, in line with their 1.6 times larger inspiratory capacities. However, when rib motion was normalized to the change in lung volume, pump-handle movements were similar for healthy participants and participants with COPD. We found no differences in bucket-handle movements between participant groups before and after normalization. Pump-handle movement was the dominant rib motion between FRC and TLC, on average four times greater than bucket-handle movement in healthy participants. For expiratory tidal volume, pump-handle movements were 20% smaller than bucket-handle movements. When normalized to tidal volume and compared with inspiratory capacity, pump-handle movements were smaller and bucket-handle movements were larger during tidal breathing. The findings suggest that the pump-handle and bucket-handle components of rib motion vary for small and large changes in lung volume.NEW & NOTEWORTHY Rib movements over inspiratory capacity are comparable for healthy participants and participants with chronic obstructive pulmonary disease when normalized to the change in lung volume. The kinematics of the ribs during tidal breathing were described from four-dimensional computed tomography images. For large changes in lung volume with inspiratory capacity, pump-handle movements of the ribs are four times greater than bucket-handle movements, whereas at tidal volume, pump-handle movements are 20% smaller than bucket-handle movements.


Effect of evacuation of Japanese residents from Wuhan, China, on preventing transmission of novel coronavirus infection: A modelling study.
In late January 2020, the Japanese government carried out three evacuations by aircraft from Wuhan, China, to avoid further cases of coronavirus disease 2019 (COVID-19) among Wuhan's Japanese residents. Evacuation by aircraft may be an effective countermeasure against outbreaks of infectious diseases, but evidence of its effect is scarce. This study estimated how many COVID-19 cases were prevented among the Japanese residents of Wuhan by the evacuation countermeasure. We constructed a SETAIR (susceptible-exposed-transitional-asymptomatic-infectious-recovered) model to capture the epidemic growth of COVID-19 cases in Wuhan to estimate the predicted number of COVID-19 cases among Wuhan's Japanese residents if evacuation had not occurred at the end of January. We used data on the number of COVID-19 cases confirmed in Hubei Province for the period Jan 20-Feb 16, 2020, and on the number of cases of Japanese residents who were evacuated by aircraft on Jan 29, 30, and 31. Eleven imported COVID-19 cases were reported on Feb 1 from among the total 566 evacuees who returned to Japan. In the case of no evacuations being made, the cumulative number of COVID-19 cases among Wuhan's Japanese residents was estimated to reach 25 (95% CI [20,29]) on Feb 8 and 34 (95% CI [28,40]) on Feb 15. A 1-week delay in the evacuation might be led to 14 additional cases and a 2-week delay to 23 additional cases. Evacuation by aircraft can contribute substantially to reducing the number of infected cases in the initial stage of the outbreak.


Adenoids and otitis media with effusion: nasopharyngeal flora.
In order to clarify the role of the microflora of the nasopharynx and adenoids as causative factors of otitis media with effusion (OME), bacteriologic species in middle ear effusions (MEEs), nasopharyngeal smears, and adenoid tissues of children with OME were cultured. The change in the microflora of the nasopharynx after adenoidectomy, and the degree of bacterial agreement between the microflora of the nasopharynx and adenoid tissue were investigated. Nasopharyngeal bacterial flora were investigated in 259 children with OME from November 1984 to November 1987. The patients were divided into two groups: group A (43 patients) underwent adenoidectomy, and group B (216 patients) had no adenoidectomy. Hemophilus influenzae, Streptococcus pneumoniae, Branhamella catarrhalis, and Staphylococcus aureus were cultured in 66.7% of nasopharyngeal smears from group B, and in 46.5% from group A. Adenoid specimens for bacteriologic investigation were obtained from 38 adenoidectomy patients at surgery. Of these, H influenzae were cultured from adenoid specimens taken from 16 of the 26 patients with OME (group C), while only three of the 12 adenoidectomy patients without OME (group D) were found to have H influenzae in their adenoid specimens. The findings of this study suggest that adenoid vegetation plays an important role in the etiology of OME.


Application of novel adsorbents synthesized with polypyrrole in magnetic solid-phase extraction of fungicides from fresh juice and environmental water.
In this work, a magnetic adsorption material based on a metal-organic framework (Fe3O4@PPy@MIL-53(Fe)) was designed and prepared, as well as used as an adsorbent for the extraction of fungicides from fresh juice and environmental water. The material was subjected to a series of characterization analyses, which showed that the material has good potential for application as an adsorbent. The main parameters such as adsorbent dosage, adsorption time, elution time, pH value, and elution solvent which could affect the experiment results were optimized. Under optimal conditions, the method exhibited linearity (R2 ≥ 0.9994) in the concentration range 10-1000 µg/L for three triazole fungicides, and LOD value ranged from 2.1 µg/L to 2.9 µg/L. In addition, the established method was applied to real samples of three fruit juices and two ambient waters, and satisfactory recoveries in the range of 78.6%-105.4% and RSDs of ≤ 5.7% were obtained.


Randomised controlled trial of a smartphone application-based dietary self-management program on haemodialysis patients.
To develop a smartphone application-based dietary self-management program for haemodialysis patients and to examine its effects on biochemical indicators, self-efficacy and quality of life. Lack of dietary management in haemodialysis patients can lead to serious complications such as oedema, hyponatremia, hyperkalaemia, hypertension, uraemia and eventually death; however, studies using smartphone applications for dietary self-management in haemodialysis patients are rare. A prospective, single-blind, randomised, controlled design with repeated measures was followed with 75 haemodialysis patients at a haemodialysis centre. Data were collected from 10 January 2017-6 May 2018. The study applied the Consolidated Standards of Reporting Trials statement. The 8-week smartphone application-based dietary self-management program was developed through collaboration with a haemodialysis equipment company. The experimental group took this program while the control group took an 8-week general program. Study variables were serum phosphorus, potassium and albumin, self-efficacy and quality of life. They were measured at pretest, and 8 weeks and 12 weeks after the programs, and analysed using two-way repeated measures analysis of variance. The smartphone application-based program significantly improved serum phosphorus, potassium, self-efficacy and quality of life over time compared with the general program. There was no significant difference in albumin level changes between the groups. The smartphone application-based dietary self-management program is an opportune and effective nursing intervention to lower serum phosphorus and potassium levels in haemodialysis patients over time. Trial registration was performed on www.cris.nih.go.kr (KCT0005366). Haemodialysis patients can easily use the smartphone application to manage their diet anytime and anywhere. They can get real-time feedback and solutions to prevent haemodialysis complications. Nurses can provide tailored high-quality care based on an individual's lifelog data from the smartphone application.


Development of a Novel Electroactive Cardiac Patch Based on Carbon Nanofibers and Gelatin Encouraging Vascularization.
Tissue engineering makes it possible to fabricate scaffolds that can help the function of defective tissues or even the most complex organs such as the heart. Carbon nanofibers (CNFs), because of their high mechanical strength and electrical properties, can improve the functional coupling of cardiomyocytes and their electrophysiological properties. In this study, electroactive CNF/gelatin (Gel) nanofibrous cardiac patches were prepared by an electrospinning method. Scanning electron microscope (SEM) evaluation of prepared scaffolds showed randomly oriented nanofibers. The electrical conductivity of the CNF/Gel scaffolds was assessed by a four-probe device and was in the semiconducting range (~ 10-5 S/m). The result of an MTT assay confirmed the excellent biocompatibility of electroactive CNF/Gel scaffolds. Also, CNF-containing scaffolds supported cardiomyocyte adhesion and increased expression of the cardiac genes including TrpT-2, Actn4, and Conx43 compared with the non-conductive counterpart. Our findings also confirmed the angiogenic potential of CNF/Gel scaffolds as compatible and electroactive platforms for cardiac tissue engineering.


Hepatectomy for liver metastases from cervical cancer with portal vein tumor thrombosis: a case report.
The prognosis of patients with liver metastasis of cervical cancer is poor with an extremely short survival period, and there have been no reports of cervical cancer complicated by portal vein tumor thrombosis (PVTT). We report a case of cervical cancer developing liver metastasis with PVTT. A 49-year-old woman developed liver metastasis from cervical cancer with PVTT. The primary tumor was locally controlled with multidisciplinary treatment, including systemic therapy, surgical resection, and radiation. However, her follow-up abdominal computed tomography results showed two irregular tumors in the liver's segments 2 and 6. From the latter lesion, a low-density filling defect extended to the posterior branch of the portal vein, suggesting PVTT. Hepatectomy of the two metastases was performed to prevent portal vein obstruction during subsequent chemotherapy. Pathological analysis revealed metastatic squamous cell carcinoma from cervical cancer that developed a tumor thrombus at the posterior branch of the portal vein. The patient received adjuvant chemotherapy, but died 10 months after surgery for recurrent liver metastasis. We present the first case of liver resection for liver metastasis from cervical cancer with PVTT. Although cervical cancer with PVTT is associated with a poor prognosis, surgical resection is a feasible option for preventing portal vein obstruction during subsequent chemotherapy.


Randomized Trial of Left Bundle Branch vs Biventricular Pacing for Cardiac Resynchronization Therapy.
Left bundle branch pacing (LBBP) is the most rapidly growing conduction system pacing technique that is capable of correcting intrinsic left bundle branch block (LBBB). As such, it is potentially an optimal alternative to cardiac resynchronization therapy (CRT) with biventricular pacing (BiVP). The authors sought to compare the efficacy of LBBP-CRT with BiVP-CRT in patients with heart failure and reduced left ventricular ejection fraction (LVEF). This is a prospective, randomized trial of patients with nonischemic cardiomyopathy and LBBB with 6-month preplanned follow-up. Crossovers were allowed if LBBP or BiVP were unsuccessful. The primary endpoint was the difference in LVEF improvement between 2 groups. The secondary endpoints included changes in echocardiographic measurements, N-terminal pro-B-type natriuretic peptide (NT-proBNP), New York Heart Association functional class, 6-minute walk distance, QRS duration, and CRT response. The study included 40 consecutive patients (20 males, mean age 63.7 years, LVEF 29.7% ± 5.6%). Crossovers occurred in 10% of LBBP-CRT and 20% of BiVP-CRT. All patients completed follow-up. Intention-to-treat analysis showed significantly higher LVEF improvement at 6 months after LBBP-CRT than BiVP-CRT (mean difference: 5.6%; 95% CI: 0.3-10.9; P = 0.039). LBBP-CRT also appeared to have greater reductions in left ventricular end-systolic volume (-24.97 mL; 95% CI: -49.58 to -0.36 mL) and NT-proBNP (-1,071.80 pg/mL; 95% CI: -2,099.40 to -44.20 pg/mL), and comparable changes in New York Heart Association functional class, 6-minute walk distance, QRS duration, and rates of CRT response compared with BiVP-CRT. LBBP-CRT demonstrated greater LVEF improvement than BiVP-CRT in heart failure patients with nonischemic cardiomyopathy and LBBB. (Left Bundle Branch Pacing Versus Biventricular Pacing for Cardiac Resynchronization Therapy [LBBP-RESYNC]; NCT04110431).


In situ forming hydrogels composed of oxidized high molecular weight hyaluronic acid and gelatin for nucleus pulposus regeneration.
Encapsulation of nucleus pulposus (NP) cells within in situ forming hydrogels is a novel biological treatment for early stage intervertebral disc degeneration. The procedure aims to prolong the life of the degenerating discs and to regenerate damaged tissue. In this study we developed an injectable oxidized hyaluronic acid-gelatin-adipic acid dihydrazide (oxi-HAG-ADH) hydrogel. High molecular weight (1900 kDa) hyaluronic acid was crosslinked with various concentrations of gelatin to synthesize the hydrogels and their viscoelastic properties were analyzed. Interactions between the hydrogels, NP cells, and the extracellular matrix (ECM) were also evaluated, as were the effects of the hydrogels on NP cell gene expression. The hydrogels possess several clinical advantages, including sterilizability, low viscosity for injection, and ease of use. The viscoelastic properties of the hydrogels were similar to native tissue, as reflected in the complex shear modulus (∼11-14 kPa for hydrogels, 11.3 kPa for native NP). Cultured NP cells not only attached to the hydrogels but also survived, proliferated, and maintained their round morphology. Importantly, we found that hydrogels increased NP cell expression of several crucial ECM-related genes, such as COL2A1, AGN, SOX-9, and HIF-1A.


Search for lithium isotope effects in neuronal HT22 cells.
Lithium has been used as a treatment for bipolar disorder for over half a century, but there has thus far been no clinical differentiation made between the two naturally occurring stable isotopes (6Li and 7Li). While the natural lithium salts commonly used in treatments are composed of a mixture of these two stable isotopes (approximately 7.59% 6Li and 92.41% 7Li), some preliminary research indicates the above two stable isotopes of lithium may have differential effects on rat behaviour and neurophysiology. Here, we evaluate whether lithium isotopes may have distinct effects on HT22 neuronal cell viability, GSK-3-β phosphorylation in HT22 cells, and GSK-3-β kinase activity. We report no significant difference in lithium isotope toxicity on HT22 cells, nor in GSK-3-β phosphorylation, nor in GSK-3-β kinase activity between the two isotopes of lithium.


The mechanism and significance of the slow changes of ventricular action potential duration following a change of heart rate.
This article reviews the effects of changes of heart rate on the ventricular action potential duration. These can be divided into short term (fractions of a second), resulting from the kinetics of recovery of membrane currents, through to long term (up to days), resulting from changes of protein expression. We concentrate on the medium-term changes (time course of the order of 100 s). These medium-term changes occur in isolated tissues and in the intact human heart. They may protect against cardiac arrhythmias. Finally, we discuss the cellular mechanisms responsible for these changes.


Phototherapeutic keratectomy versus epithelial debridement combined with anterior stromal puncture or diamond burr for recurrent corneal erosions.
To compare outcomes of phototherapeutic keratectomy (PTK) versus epithelial debridement combined with anterior stromal puncture (ASP) or diamond burr for the treatment of recurrent corneal erosions (RCES) in a large tertiary centre. Patients with a diagnosis of RCES secondary to trauma or epithelial basement membrane dystrophy who underwent a surgical procedure between 2009 and 2019 were included in the study. The following data were collected: demographics, ocular history, prior medical treatment, ocular surgeries, intervention, complete epithelialization at postoperative week 1, recurrences, and complications. Recurrence was defined as either an objective finding of a corneal epithelial defect or symptoms suggestive of recurrent epithelial erosion on history. Recurrence rate and time to epithelialization were compared between groups. A total of 97 eyes (73 patients) were included in the study. Mean patient age was 51 ± 16.1 years, and mean follow-up was 474 days. RCES was secondary to epithelial basement membrane dystrophy in 80% (n = 78 of 97), trauma (15%, n = 15 of 97), or idiopathic (4%, n = 4 of 97). Epithelial debridement with ASP was performed in 34 eyes (35%), diamond burr in 33 eyes (33%), and PTK in 30 eyes (31%). Compared with epithelial debridement with ASP (recurrence 29.4%), the recurrence rate was significantly lower for both the diamond burr (9.1%, p = 0.031) and PTK groups (10%, p = 0.048). The diamond burr and PTK groups also had a significantly higher rate of complete epithelialization at 1 week (p < 0.05). Compared with epithelial debridement with ASP, diamond burr and PTK have significantly lower rates of recurrence and time to epithelialization and may be considered first for surgical management of RCES.


Intraventricular trifascicular block verified by His bundle electrocardiography.
A patient with the combination of right bundle branch block and intermittent left anterior and left posterior hemiblock is presented. His bundle recordings proved that this type of intraventricular conduction defect appeared when the two left fascicles were damaged partially, and to a varying degree. The recordings also revealed a Grade 2 A-V block distal to the A-V node. The mechanism is discussed.


Murine models of uremic cardiomyopathy as a necessary tool to unravel mechanisms involved in cardiorenal syndrome.
Chronic kidney disease (CKD) and cardiovascular disease frequently run in parallel. Herein, Soppert et al. provide an interesting meta-analysis of the effects of CKD on cardiac remodeling and/or function in mice based on the model, strain, and duration. The authors sought to determine the most appropriate experimental model to unravel the specific underlying pathologic mechanisms involved in cardiac damage in CKD (single hit) or to investigate new strategies to prevent CKD-induced cardiovascular disease (multifactorial hits representing cardiovascular comorbidities of patients with CKD).


Effects of low-temperature stress on the metabolism of phosphatidylglycerol molecular species in Dunaliella salina.
A detailed analysis was made of individual phosphatidylglycerol (PG) molecular species isolated from microsomes and chloroplasts at various times after labeling Dunaliella salina cells with [14C]palmitic, [14C]oleic, or [14C]lauric acid. The patterns of [14C]fatty acid incorporation were in agreement with PG being formed by the "eucaryotic" type pathway in microsomes and the "procaryotic" type pathway in chloroplasts. In Dunaliella, which lacks a quantitatively significant flux of eucaryotic-type lipids from microsomes into chloroplast glycolipids, indications were found for a more subtle movement of microsomally synthesized PG into the chloroplasts. This transfer was more evident in cells stressed by exposure to 12 degrees C than it was at 30 degrees C, and may afford a mechanism for recruiting key microsomal PG molecular species toward low-temperature acclimation in chloroplasts.


Elderberry diet ameliorates motor function and prevents oxidative stress-induced cell death in rat models of Huntington disease.
Huntington's disease (HD) is an inherited neurodegenerative disorder which begins in the striatum and then spreads to other neural areas. Known as a progressive movement cognitive disorder, HD has no efficient therapy. Although the exact mechanism of HD is still unknown, several different etiological processes such as oxidative stress have been shown to play critical roles. Also, the current evidence indicates a strong correlation between immune activation and neural damage induced by neuroinflammatory and apoptotic agents in neurodegenerative disorders. Thus, natural products like Elderberry (EB) could be considered as a novel and potential therapeutic candidate for the treatment of this disease. In this study EB was added to the daily ration of ordinary rats for two months in order to ameliorate inflammatory and oxidative responses in rats injected with 3-nitropropionic acid (3-NP) in an experimental model of HD. Using Rotarod and electromyography setups, we showed that EB diet significantly recovered motor failure and muscle incoordination in 3-NP injected rats compared to the control group. Also, the molecular findings implied that EB diet led to a significant drop in 3-NP induced growth in caspase-3 and TNF-α concentration. The treatment also improved striatal antioxidative capacity by a significant reduction in ROS and a remarkable rise in GSH, which might be correlated with motor recovery in the tests. In sum, the findings demonstrate the advantages of EB treatment in the HD rat model with a score of beneficial anti-oxidative and anti-inflammatory effects.


Synthesis and Characterization of H3PW12O40 and H3PMo12O40 Nanoparticles by a Simple Method.
In this study H3PW12O40·9H2O and H3PMo12O40·6H2O (HPA) particles were changed into nano forms by heat-treatment in an autoclave as a simple, repaid, inexpensive and one step method. The particle size of these nanoparticles was around 25 nm. The as-synthesized nanostructures were characterized by dynamic light scattering, X-ray powder diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy and inductively coupled plasma analyzer. Thermal stability of nanoparticles was surveyed by thermal gravimeter analyse. Acidity of prepared nanoparticles was investigated by pyridine adsorption method. Results showed rising acidity by declining particle size of HPA.


The release of pancreatic polypeptide by CCK-octapeptide and some analogues in the dog.
In dogs with gastric and pancreatic Thomas fistulas the effect of different cholecystokinin-like peptides upon pancreatic polypeptide (PP) release was studied in three ways: (a) Plasma PP concentrations were determined by radioimmunoassay in response to 135 pmol/kg/h of the synthetic C-terminal octapeptide of cholecystokinin (CCK-OP) (A), of three of its analogues (B, C, D) where methionine has been replaced by methoxinine, and in response to 45 pmol/kg/h of caerulein. The greatest rise in plasma PP concentration expressed as delta PP was achieved with caerulein (327 +/- 37 pM), when taking into account the threefold smaller dose used, followed by CCK-OP (536 +/- 67 pM) and analogues B (343 +/- 51 pM), C (87 +/- 46 pM), and D (32 +/- 15 pM). The order of potency with respect to stimulation of exocrine pancreatic secretion was the same: E and A precede B, C, and D. delta PP correlated linearly with the pancreatic protein output (r = 0.98, p less than 0.01). (b) CCK-OP was infused in four doses of 35, 70, 135, and 270 pmol/kg/h, and plasma PP concentrations and exocrine pancreatic secretion were monitored. The correlation between pancreatic protein output and delta PP was very close (r = 0.98, p less than 0.01). (c) Atropine sulfate (0.1 mg/kg, i.v.) reduced the PP response to the 135 pmol/kg/h dose of CCK-OP by 61%. We conclude from this that CCK-OP and related peptides do release PP and that their effect on exocrine pancreatic secretion is closely correlated with their PP-releasing capacity. The PP release may therefore be used as an indicator of the CCK-like activity of CCK fragments and analogues. CCK-OP may well represent one of the humoral stimulatory factors contributing to the release of PP, but this action appears to depend on a cholinergic background.


Surgical and pathogenetic considerations of frontal sinus fungus ball.
Fungus ball (FB) is an non-invasive form of mycosis, that generally affects immunocompetent and non-atopic subjects. Involvement of the frontal sinus is extremely rare. We report two cases with frontal sinus fungus ball that underwent endoscopic endonasal frontal Draf type IIb or III sinusotomy with complete removal of the cheesy clay-like material. There were no intra-operative or postoperative complications, and no recurrence of disease was evident during the follow-up of 51 and 26 months, respectively. The Draf type IIb or type III frontal sinusotomy seems to be highly effective for the treatment of frontal sinus FB and can represent a valid alternative to the traditional external approaches.


A novel variant in the COL6A1 gene causing Ullrich congenital muscular dystrophy in a consanguineous family: a case report.
Collagen VI-related dystrophies are a subtype of congenital muscular dystrophy caused by pathogenic variants in COL6A1, COL6A2 or COL6A3 genes affecting skeletal muscles and connective tissue. The clinical phenotype ranges from the milder Bethlem myopathy to the severe Ullrich congenital muscular dystrophy (UCMD). Herein, we report the first consanguineous Sri Lankan family with two children affected with UCMD due to a novel variant in the COL6A1 gene. Two sisters, aged 10-years and 7-years, presented with progressive, bilateral proximal muscle weakness. Both probands had delayed motor milestones and demonstrated difficulty in standing from a squatting position, climbing stairs and raising arms above the shoulders. Cognitive, language and social development were age appropriate. Examination showed proximal muscle weakness of the upper and lower extremities and hyperlaxity of the wrist and fingers in both with some variability in clinical severity noted between the two siblings. Serum creatine kinase levels were elevated, and electromyography showed low polyphasic motor unit potentials in the 10-year-old and myopathic features with short duration motor unit potentials with no polyphasia in the 7-year-old. Whole exome sequencing (WES) was performed and a novel, homozygous missense, likely pathogenic variant in exon 25 of COL6A1 gene [NM_001848: c.1667G > T;NP_001839.2:p.Gly556Val] was identified in both probands. This variant was validated by Sanger sequencing in proband 1 as well as proband 2, and the parents and an unaffected sibling were found to be heterozygote carriers for the same variant. The findings in this family add to the expanding number of COL6A1 variants identified and provides a better understanding of the genotype-phenotype correlations associated with UCMD.


Diagnostic performance of the 2021 Korean thyroid imaging reporting and data system in pediatric thyroid nodules.
To evaluate the diagnostic performance of 2021 K-TIRADS biopsy criteria for detecting malignant thyroid nodules in a pediatric population, making comparisons with 2016 K-TIRADS. This retrospective study included pediatric patients with histopathologically confirmed diagnoses. The diagnostic performance of 2021 K-TIRADS was compared with that of 2016 K-TIRADS. Simulation studies were performed by changing biopsy cut-off sizes for K-TIRADS 5 to 1.0 cm (K-TIRADS5-1.0cm) and 0.5 cm (K-TIRADS5-0.5cm), and for K-TIRADS 4 to 1.0 cm (K-TIRADS4-1.0cm) and 1.0-1.5 cm (K-TIRADS4-1.0~1.5cm). Subgroup analysis was performed in small (< 1.5 cm) and large nodules (≥ 1.5 cm). Two hundred seventy-seven thyroid nodules (54.9% malignant) from 221 pediatric patients were analyzed. All simulated 2021 K-TIRADS showed higher accuracy than 2016 K-TIRADS. Compared with 2021 K-TIRADS5-1.0cm, 2021 K-TIRADS5-0.5cm showed lower specificity (51.6% vs. 47.9%; p = 0.004) but higher sensitivity (77.2% vs. 90.3%; p < 0.001) and accuracy (62.7% vs. 68.9%; p < 0.001). Compared with 2021 K-TIRADS4-1.0cm, 2021 K-TIRADS4-1.0~1.5cm showed higher specificity (44.9% vs. 47.9%; p = 0.018) without significant difference in other diagnostic measures. Compared with 2016 K-TIRADS, 2021 K-TIRADS (biopsy cut-offs, 0.5 cm for K-TIRADS 5; 1.0-1.5 cm for K-TIRADS 4) showed higher sensitivity (34.0% vs. 67.3%; p < 0.001) while maintaining specificity (89.4% vs. 88.2%; p = 0.790) in small nodules, and higher specificity (5.9% vs. 25.4%; p < 0.001) while maintaining sensitivity (100% vs. 98.7%; p = 0.132) in large nodules. In pediatric patients, 2021 K-TIRADS showed superior diagnostic accuracy to 2016 K-TIRADS, especially with a biopsy cut-off of 0.5 cm for K-TIRADS 5 and 1.0-1.5 cm for K-TIRADS 4. • All simulated 2021 K-TIRADS showed higher accuracy than 2016 K-TIRADS. • 2021 K-TIRADS with cut-off size for K-TIRADS 5 of 0.5 cm showed lower specificity but higher sensitivity and accuracy than that of 1.0 cm. • Compared with 2016 K-TIRADS, 2021 K-TIRADS (biopsy cut-offs, 0.5 cm for K-TIRADS 5; 1.0-1.5 cm for K-TIRADS 4) showed higher sensitivity while maintaining specificity in small nodules, and higher specificity while maintaining sensitivity in large nodules.


The Human Genome Project: an overview of ethical issues and public policy concerns.
The possibilities of advancement from the Human Genome Project seem endless. But even though we are amazingly similar genetically to other animals, including the mouse, we are uniquely human. And our humanness is our greatest gift. The knowledge of genetic linkages and of how life works does not diminish our religious beliefs or our value system. Understanding the mechanics of human physiology does not decrease the power and beauty of human life. Quite the contrary, this knowledge helps to chart the course in a quest to understand what it means to be human. Let us honor the beauty and uniqueness of human life by making ethically sound decisions surrounding the advances made in this fantastic journey called the Human Genome Project.


Demonstration of a software package for the reconstruction of the dynamically changing structure of the human heart from cone beam x-ray projections.
The Dynamic Spatial Reconstructor (DSR) is a device constructed at the Biodynamics Research Unit of the Mayo Clinic for (among other things) the visualization of the beating heart inside the intact thorax. The device consists of 28 rotating X-ray sources arranged on a circular arc at 6 degrees intervals (total span 162 degrees) and a matching set of 28 imaging systems. The whole thorax of the patient is projected onto the two-dimensional screen of the imaging systems by cone beams of X rays from the sources. All of the X-ray sources are switched on and off within a total period of 10 milliseconds. The Medical Image Processing Group at the State University of New York at Buffalo has developed a software package for the design and evaluation of algorithms to be used by the DSR. In this paper we illustrate the operation of the package and a particular algorithm for the reconstruction of the dynamically changing structure of the heart from data collected by the DSR.


Data used for detection and tracking of dynamic objects for visually impaired people.
This paper presents in detail the methodology for the detection and tracking of dynamic objects from the article in press (A new methodology applied to dynamic object detection and tracking systems for visually impaired people [1]). In order to validate this methodology, four different architectures have been designed in this paper. These architectures have implemented the techniques of pattern recognition, optical flow, background subtraction and color tracking to enable comparison and to see which is the most appropriate in a given environment. In this paper we also present a method created to quantify the effectiveness of each architecture implemented.


Association of Hypertension and Diabetes with Ischemic Heart Disease and Stroke Mortality in India: The Million Death Study.
The cardiovascular outcomes of hypertension and diabetes in India have never been studied at the national level. We conducted a nationally-representative proportional mortality study to measure the associations of hypertension and diabetes with premature mortality due to ischemic heart disease (IHD) and stroke among Indian adults. We determined causes of death by verbal autopsy from 2001-14 among 2.4 million households. We defined cases as those who died of the study outcomes and controls as those who died of injuries, respiratory causes, or cancer. We used multivariable logistic regression models to compute adjusted odds ratios (OR) measuring the association of hypertension and diabetes with IHD or stroke mortality, population-attributable fractions (PAF), and time trends. The mean age at death was 55.6 (standard deviation 9.9) years for IHD, 58.2 (9.0) years for stroke, and 46.8 (injury) to 59.8 (respiratory) years for controls. There were more men among both the cases (IHD: 70.1%; stroke: 59.0%) and controls (injury: 76.6%; cancer: 55.4%; respiratory: 59.8%). Hypertension was associated with six- to eight-fold increases in the odds of IHD (OR 5.9, 99% CI 5.6-6.2) and stroke mortality (7.9, 7.4-8.5). Diabetes was associated with double the odds (1.9, 1.7-2.0) of IHD mortality and increased odds of stroke mortality (1.6, 1.4-1.7). Hypertension accounted for an increasing PAF of IHD mortality and decreasing PAF of stroke mortality. Diabetes was associated with relatively lower PAFs and variable time trends. Hypertension is associated with an unexpectedly high burden of cardiovascular mortality, and contributes to an increasing proportion of IHD deaths and a decreasing proportion of stroke deaths. Better management of hypertension and diabetes is urgently required to reduce premature cardiovascular mortality.


Identifying Racial, Ethnic, and Socioeconomic Inequities in the Use of Novel P2Y12 Inhibitors After Percutaneous Coronary Intervention.
Novel P2Y12 inhibitors prasugrel and ticagrelor were approved for patients with acute coronary syndrome (ACS) in 2009 and 2011, respectively. We assessed the association of racial, ethnic, and socioeconomic factors with initiation of and adherence to novel P2Y12 inhibitors in a commercially insured population. We performed a retrospective cohort analysis of adults undergoing percutaneous coronary intervention with placement of a drug-eluting stent, stratified by ACS status, between January 2008 and December 2016 using Clinformatics Data Mart (OptumInsight). We estimated multivariable logistic regression models to identify factors associated with the initiation of clopidogrel vs novel P2Y12 inhibitors as well as subsequent 6-month medication adherence, assessed via pharmacy records. A total of 55,664 patients were included in the analysis. Hispanic ethnicity was independently associated with the initiation of clopidogrel compared with novel P2Y12 inhibitors among ACS patients (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.04-1.36; P<.01). ACS patients with an annual median household income of over $100,000 were less likely to be started on clopidogrel when compared with those who earned less than $40,000 (OR, 0.67; 95% CI, 0.61-0.75; P<.01). Black race, Hispanic ethnicity, and lower household income were each associated with significantly reduced odds of P2Y12 inhibitor adherence. Hispanic ethnicity and lower household income were associated with novel P2Y12 inhibitor initiation, and non-White race and ethnicity were associated with lower P2Y12 inhibitor adherence over 6-month follow-up. These findings highlight continued inequity of care, even in an insured population, and point to a need for new strategies to close these gaps.


Integration of functional imaging in brachytherapy.
Functional imaging allows the evaluation of numerous biological properties that could be considered at all steps of the therapeutic management of patients treated with brachytherapy. Indeed, it enables better initial staging of the disease, and some parameters may also be used as predictive biomarkers for treatment response, allowing better selection of patients eligible for brachytherapy. It may also improve the definition of target volumes with the aim of dose escalations by dose-painting. Finally, it could be useful during the follow-up to assess response to treatment. In this review, we report how functional imaging is integrated at the present time during the brachytherapy procedure, and what are its potential future contributions in the main tumour locations where brachytherapy is recommended. Functional imaging has great potential in the contact of brachytherapy, but still, several issues remain to be resolved before integrating it into clinical practice, especially as a biomarker or in dose painting strategies.


QDataSet, quantum datasets for machine learning.
The availability of large-scale datasets on which to train, benchmark and test algorithms has been central to the rapid development of machine learning as a discipline. Despite considerable advancements, the field of quantum machine learning has thus far lacked a set of comprehensive large-scale datasets upon which to benchmark the development of algorithms for use in applied and theoretical quantum settings. In this paper, we introduce such a dataset, the QDataSet, a quantum dataset designed specifically to facilitate the training and development of quantum machine learning algorithms. The QDataSet comprises 52 high-quality publicly available datasets derived from simulations of one- and two-qubit systems evolving in the presence and/or absence of noise. The datasets are structured to provide a wealth of information to enable machine learning practitioners to use the QDataSet to solve problems in applied quantum computation, such as quantum control, quantum spectroscopy and tomography. Accompanying the datasets on the associated GitHub repository are a set of workbooks demonstrating the use of the QDataSet in a range of optimisation contexts.


Rg3-enriched Korean Red Ginseng extract inhibits blood-brain barrier disruption in an animal model of multiple sclerosis by modulating expression of NADPH oxidase 2 and 4.
Multiple sclerosis (MS) and its animal model, the experimental autoimmune encephalomyelitis (EAE), are primarily characterized as dysfunction of the blood-brain barrier (BBB). Ginsenoside-Rg3-enriched Korean Red Ginseng extract (Rg3-KRGE) is known to exert neuroprotective, anti-inflammatory, and anti-oxidative effects on neurological disorders. However, effects of Rg3-KRGE in EAE remain unclear. Here, we investigated whether Rg3-KRGE may improve the symptoms and pathological features of myelin oligodendroglial glycoprotein (MOG)35-55 peptide - induced chronic EAE mice through improving the integrity of the BBB. Rg3-KRGE decreased EAE score and spinal demyelination. Rg3-KRGE inhibited Evan's blue dye leakage in spinal cord, suppressed increases of adhesion molecule platelet endothelial cell adhesion molecule-1, extracellular matrix proteins fibronection, and matrix metallopeptidase-9, and prevented decreases of tight junction proteins zonula occludens-1, claudin-3, and claudin-5 in spinal cord following EAE induction. Rg3-KRGE repressed increases of proinflammatory transcripts cyclooxygenase-2, inducible nitric oxide synthase, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-alpha, but enhanced expression levels of anti-inflammatory transcripts arginase-1 and IL-10 in the spinal cord following EAE induction. Rg3-KRGE inhibited the expression of oxidative stress markers (MitoSOX and 4-hydroxynonenal), the enhancement of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and NOX4, and NADPH activity in the spinal cord of chronic EAE mice. Furthermore, apocynin, a NOX inhibitor, mimicked beneficial effects of Rg3-KRGE in chronic EAE mice. Our findings suggest that Rg3-KRGE might alleviate behavioral symptoms and pathological features of MS by improving BBB integrity through modulation of NOX2/4 expression.


Dinuclear gold(I) complexes based on carbene and diphosphane ligands: bis[2-(dicyclohexylphosphano)ethyl]amine complex inhibits the proteasome activity, decreases stem cell markers and spheroid viability in lung cancer cells.
Three new dinuclear gold(I) complexes (1-3) containing a carbene (1,3-Bis(2,6-di-isopropylphenyl)imidazol-2-ylidene (IPr)) and diphosphane ligands [bis(1,2-diphenylphosphano)ethane (Dppe), bis(1,3-diphenylphosphano)propane (Dppp) and bis[2-(dicyclohexylphosphano)ethyl]amine (DCyPA)], were synthesized and characterized by elemental analysis and, ESI-MS, mid FT-IR and NMR spectroscopic methods. The structures of complexes 2 and 3 were determined by X-ray crystallography, which revealed that the complexes are dinuclear having gold(I) ions linearly coordinated. The anticancer activities of the complexes (1-3) were evaluated in lung (A549), breast (MC-F7), prostate (PC-3), osteosarcoma (MG-63) and ovarian (A2780 and A2780cis) cancer models. Growth inhibition by the new complexes was higher than cisplatin in all cell lines tested. The mechanism of action of complex 3 was investigated in A549 cells using 2-dimensional (2D) models and 3D-multicellular tumor spheroids. Treatment of A549 cells with complex 3 caused: the induction of apoptosis and the generation of reactive oxygen species; the cell cycle arrest in the G0/G1 phase; the inhibition of both the proteasome and the NF-kB activity; the down-regulation of lung cancer stem cell markers (NOTCH1, CD133, ALDH1 and CD44). Complex 3 was more active than cisplatin also in 3D models of A549 lung cancer cells.


In Situ Growth of Ultrathin Ni(OH)2 Nanosheets as Catalyst for Electrocatalytic Oxidation Reactions.
Development of electrocatalysts that are capable of efficiently oxidizing biomass-derived 5-hydroxymethylfurfural (HMF) into 2,5-furandicarboxylic acid (FDCA) is critically important for production of degradable plastics via non-fossil routes. In this study, a facile and scalable immersion synthetic approach has been developed to grow ultrathin nickel hydroxide nanosheets in situ on commercial nickel foam (Ni(OH)2 /NF) as an anode for the electrocatalytic oxidation of HMF to FDCA with complete HMF conversion, 100 % FDCA yield, and >99 % faradaic efficiency at 1.39 V (vs. RHE) within 90 min. Mechanistic studies reveal that the initial oxidation of HMF takes place at the carbonyl group and FDCA is generated through two further oxidation steps. Impressively, the synthesized Ni(OH)2 /NF can also be used to electrocatalytically oxidize other alcohol/aldehyde-containing compounds to the targeted products in alkaline medium with 100 % yield and >94 % faradaic efficiency under a low oxidation potential of 1.39 V (vs. RHE) within short reaction times.


Identification of prognostic immune cells and potential immune-related markers in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common and deadly tumors worldwide. Immunotherapy has emerged as a promising strategy for HCC treatment, and understanding the immune microenvironment of HCC provides a theoretical basis for identifying new immune targets. However, the roles of immune components and their regulatory mechanisms in HCC require further clarified. By analyzing HCC expression profiles from The Cancer Genome Atlas (TCGA) database, we depicted the proportion profile of immune cells for each sample using the software CIBERSORTx. Using R packages, we also characterized the distribution of differentially expressed genes (DEGs) in immune cells, calculated the correlation coefficient between immune cells and common DEGs, and analyzed their biology function by Gene-Ontology analysis. We found that seven immune cell types were related to the overall survival of HCC patients, and identified 3,692 differentially expressed immune-related genes, predominantly functioning in nucleic acid processing and metabolism. Moreover, 14 DEGs were identified as common candidates related to immune cells and overall survival. Our study not only presents an overview of the immune features of the microenvironment of HCC, but also provides potential targets related to immune components.


Successful treatment of primary cutaneous localized amyloidosis with a combined therapy of ablative fractionated CO2 laser, topical retinoid, corticosteroids and levovitamin C: Five cases with two-year follow-up.
Primary cutaneous localized amyloidosis (PCLA) is a pruritic disorder with no radical cure. We trialed a combined therapy of ablative fractionated CO2 laser, topical retinoid, corticosteroids and levovitamin C on five patients. All patients responded with no intolerant signs. Two-year follow-up visit showed no recurrence. This might be a effective method awaiting more samples for further stronger evidence.


Genomewide comparison and novel ncRNAs of Aquificales.
The Aquificales are a diverse group of thermophilic bacteria that thrive in terrestrial and marine hydrothermal environments. They can be divided into the families Aquificaceae, Desulfurobacteriaceae and Hydrogenothermaceae. Although eleven fully sequenced and assembled genomes are available, only little is known about this taxonomic order in terms of RNA metabolism. In this work, we compare the available genomes, extend their protein annotation, identify regulatory sequences, annotate non-coding RNAs (ncRNAs) of known function, predict novel ncRNA candidates, show idiosyncrasies of the genetic decoding machinery, present two different types of transfer-messenger RNAs and variations of the CRISPR systems. Furthermore, we performed a phylogenetic analysis of the Aquificales based on entire genome sequences, and extended this by a classification among all bacteria using 16S rRNA sequences and a set of orthologous proteins.Combining several in silico features (e.g. conserved and stable secondary structures, GC-content, comparison based on multiple genome alignments) with an in vivo dRNA-seq transcriptome analysis of Aquifex aeolicus, we predict roughly 100 novel ncRNA candidates in this bacterium. We have here re-analyzed the Aquificales, a group of bacteria thriving in extreme environments, sharing the feature of a small, compact genome with a reduced number of protein and ncRNA genes. We present several classical ncRNAs and riboswitch candidates. By combining in silico analysis with dRNA-seq data of A. aeolicus we predict nearly 100 novel ncRNA candidates.


Quantitative high-throughput screening data analysis: challenges and recent advances.
In vitro HTS holds much potential to advance drug discovery and provide cell-based alternatives for toxicity testing. In quantitative HTS, concentration-response data can be generated simultaneously for thousands of different compounds and mixtures. However, nonlinear modeling in these multiple-concentration assays presents important statistical challenges that are not problematic for linear models. The uncertainty of parameter estimates obtained from the widely used Hill equation model can be extremely large when using standard designs. Failure to properly consider standard errors of these parameter estimates would greatly hinder chemical genomics and toxicity testing efforts. In this light, optimal study designs should be developed to improve nonlinear parameter estimation; or alternative approaches with reliable performance characteristics should be used to describe concentration-response profiles.


Investigation of the Relationship between the S1 Domain and Its Molecular Functions Derived from Studies of the Tertiary Structure.
S1 domain, a structural variant of one of the "oldest" OB-folds (oligonucleotide/oligosaccharide-binding fold), is widespread in various proteins in three domains of life: Bacteria, Eukaryotes, and Archaea. In this study, it was shown that S1 domains of bacterial, eukaryotic, and archaeal proteins have a low percentage of identity, which indicates the uniqueness of the scaffold and is associated with protein functions. Assessment of the predisposition of tertiary flexibility of S1 domains using computational and statistical tools showed similar structural features and revealed functional flexible regions that are potentially involved in the interaction of natural binding partners. In addition, we analyzed the relative number and distribution of S1 domains in all domains of life and established specific features based on sequences and structures associated with molecular functions. The results correlate with the presence of repeats of the S1 domain in proteins containing the S1 domain in the range from one (bacterial and archaeal) to 15 (eukaryotic) and, apparently, are associated with the need for individual proteins to increase the affinity and specificity of protein binding to ligands.


An accurate single descriptor for ion-π interactions.
Non-covalent interactions between ions and π systems play an important role in molecular recognition, catalysis and biology. To guide the screen and design for artificial hosts, catalysts and drug delivery, understanding the physical nature of ion-π complexes via descriptors is indispensable. However, even with multiple descriptors that contain the leading term of electrostatic and polarized interactions, the quantitative description for the binding energies (BEs) of ion-π complexes is still lacking because of the intrinsic shortcomings of the commonly used descriptors. Here, we have shown that the impartment of orbital details into the electrostatic energy (coined as OEE) makes an excellent single descriptor for BEs of not only spherical, but also multiply-shaped, ion-π systems, highlighting the importance of an accurate description of the electrostatic interactions. Our results have further demonstrated that OEEs from a low-level method could be calibrated to BEs from a high-level method, offering a powerful practical strategy for an accurate prediction of a set of ion-π interactions.


Monoclonal antibody that recognizes a domain on heterogeneous nuclear ribonucleoprotein K and PTB-associated splicing factor.
hnRNP K protein is a member of the heterogeneous nuclear protein (hnRNP) complex that, besides its function as a translational regulator of human mRNA, is also considered to be a transcription factor involved in tumorigenesis. PSF is a protein part of the human spliceosome and essential in RNA splicing. Here we report the generation of one monoclonal antibody GG6H9.1C3 that recognized both hnRNP K and PSF proteins using Western blot analysis, flow cytometry, and immunocytochemistry.


Pulmonary single circulation dilution curves of T-1824, sodium, and tritiated water in intact piglets.
In order to assess pulmonary endothelial permeability to sodium in the immature lung, 15 multiple indicator dilution curves were done in eight intact piglets. An indicator bolus consisting of T-1824, 22Na, and tritiated water (THO) was delivered into the right atrium and blood was sampled from the aorta. The concentration of sodium, expressed as a fraction of the quantity injected and of the corresponding fractional concentration of T-1824, was averaged for the samples prior to recirculation. The permeability-surface area product calculated from these data is 2.0 X 10(-5) cm sec-1, and is virtually identical with the value reported elsewhere for adult dogs. Extravascular lung water obtained from the triated water and T-1824 curves averaged 64%, whereas that obtained from the 22Na and T-1824 curves averaged 23% of blood-free lung water.


Effect of nicotine on 3-nitropropionic acid-induced oxidative stress in synaptosomes.
In this paper, the effect of nicotine on the oxidative changes produced by 3-nitropropionic acid (20 mg/kg i.p./day for 4 days) in striatal and cortical synaptosomes of Wistar rats was studied. The effects of 3-nitropropionic acid were evaluated as changes in the quantity of protein carbonyl groups, lipid peroxidation products, superoxide distumase activity and reduced succinate dehydrogenase activity. All changes were prevented by the pre-injection of nicotine (1.5 mg/kg i.p./day), beginning 4 days before and continuing for 4 days after the first injection of 3-nitropropionic acid. These findings indicate that: (i) 3-nitropropionic acid induces a state of oxidative stress in cortical and striatal synaptosomes and (ii) nicotine prevents oxidative stress induced by 3-nitropropinonic acid. In conclusion, the results show the ability of nicotine to modify neural response to 3-nitropropionic acid with the protective mechanism likely involving the antioxidative processes of nicotine.


The Study of Release Mechanisms for Drug in Cyclodextrin Metal-Organic Frameworks.
γ-Cyclodextrin metal-organic frameworks (γCDMOF) recently emerged as biofriendly, highly porous, and crystalline materials with potential applications in drug delivery. However, little is known about their drug entrapment and release characteristics, which are key parameters in the design of drug carriers. The macroscopic properties of a material are determined by its microstructure. Thus, the characteristics of the constitutive units of the cubic crystalline γCDMOF determine their drug loading and release behaviors. In this study, the release profile of prednisolone (PNS) form γCDMOF was predicted, and the mechanism was analyzed based on the γCDMOF molecular structure. For the first time, experimental, molecular simulation, and mathematical modeling methods were combined to gain insights into the drug distribution in cubic porous crystals of γCDMOF as well as on drug release kinetics. The predicted release profile was in good agreement with the experimental results, showing that the modeling method was reliable. The methodology developed here could provide a reference for further investigations of drug penetration and release in supramolecular systems.


Trial registration and selective outcome reporting in Endodontic Research: Evidence over a 5-year period.
To assess the prevalence of registration of clinical trials in endodontic research and to identify outcome reporting discrepancies between trial registration entries and respective final publications. Associations with publication characteristics, such as journal, year of publication, origin, number of centres and authors, funding and statistical significance of the findings, were also sought. All reports of endodontic randomized controlled trials (RCTs) published in 4 endodontic specialty and 4 general dental journals from 1 January 2016 to 31 December 2020 were identified. Trial registration frequency patterns were assessed for the included RCTs, whilst for the ones registered, outcome reporting discrepancies were recorded. Article characteristics such as year of publication, geographic region, number of centres, authors participating in the publication, funding, type of registration and others were identified. Descriptive statistics and univariable/multivariable logistic regression were performed to examine the effect of study characteristics on identified registration practices. One hundred and fifty-five RCTs were included, with the majority published in specialty journals (121/155; 78.1%). A total of 42.6% of the identified RCTs was registered (66/155), mostly retrospectively (38/66; 57.6%). There was strong evidence that each additional year for more recent publication accounted for 1.42 times higher odds of being registered (adjusted Odds Ratio = 1.42; 95%CI: 1.11, 1.80; p = .004). More than 1/3 of registered RCTs presented outcome reporting discrepancies (24/66; 36.4%), whilst such inconsistencies were almost evenly distributed between primary and secondary outcomes. Trial registration policies in endodontic research should be reviewed and active endorsement of prospective registration practices should be prioritized for better clarity and transparency of the disseminated research. Outcome reporting discrepancies shall thus be eliminated, offering increased credibility in research findings and eliminating bias in this respect.


Fusobacterium nucleatum outer membrane vesicles activate autophagy to promote oral cancer metastasis.
Metastasis is an important cause of high mortality and lethality of oral cancer. Fusobacterium nucleatum (Fn) can promote tumour metastasis. Outer membrane vesicles (OMVs) are secreted by Fn. However, the effects of Fn-derived extracellular vesicles on oral cancer metastasis and the underlying mechanisms are unclear. We aimed to determine whether and how Fn OMVs mediate oral cancer metastasis. OMVs were isolated from brain heart infusion (BHI) broth supernatant of Fn by ultracentrifugation. Tumour-bearing mice were treated with Fn OMVs to evaluate the effect of OMVs on cancer metastasis. Transwell assays were performed to determine how Fn OMVs affect cancer cell migration and invasion. The differentially expressed genes in Fn OMV-treated/untreated cancer cells were identified by RNA-seq. Transmission electron microscopy, laser confocal microscopy, and lentiviral transduction were used to detect changes in autophagic flux in cancer cells stimulated with Fn OMVs. Western blotting assay was performed to determine changes in EMT-related marker protein levels in cancer cells. Fn OMVs' effects on migration after blocking autophagic flux by autophagy inhibitors were determined by in vitro and in vivo experiments. Fn OMVs were structurally similar to vesicles. In the in vivo experiment, Fn OMVs promoted lung metastasis in tumour-bearing mice, while chloroquine (CHQ, an autophagy inhibitor) treatment reduced the number of pulmonary metastases resulting from the intratumoral Fn OMV injection. Fn OMVs promoted the migration and invasion of cancer cells in vivo, leading to altered expression levels of EMT-related proteins (E-cadherin downregulation; Vimentin/N-cadherin upregulation). RNA-seq showed that Fn OMVs activate intracellular autophagy pathways. Blocking autophagic flux with CHQ reduced in vitro and in vivo migration of cancer cells induced by Fn OMVs as well as reversed changes in EMT-related protein expression. Fn OMVs not only induced cancer metastasis but also activated autophagic flux. Blocking autophagic flux weakened Fn OMV-stimulated cancer metastasis.


Tibial physeal changes in renal osteodystrophy: lateral Blount's disease.
In a group of 27 children with chronic renal failure and renal osteodystrophy, we identified eight patients with significant involvement of the proximal tibial physis (15 knees). The radiographic changes observed were analogous to those observed in tibia vara (Blount's disease) but involved the lateral physis rather than the medial physis. This observation is offered as further evidence that such changes are related to eccentric weight-bearing rather than alternative etiologies such as trauma, infection, or heredity.


Secondary structure analysis of ITS2 in the rDNA of three Indian paramphistomid species found in local livestock.
Of paramphistomid trematodes, three species viz., Homalogaster paloniae, Calicophoron calicophorum and Orthocoelium streptocoelium are commonly prevalent in bovine hosts in Northeast India. The aim of the present study was to genetically characterise these species using rDNA second internal transcribed spacer (ITS2) so as to supplement the morphological criteria substantiated by molecular findings. The annotated ITS2 region from H. paloniae, C. calicophorum and O. streptocoelium were found to be 289 bp, 288 bp and 288 bp long, respectively. On comparison, the Indian isolates of the three species were observed to have a maximum identity of 99% with each of their respective counterparts from Japan. The secondary structure models were inferred using minimum free energy modelling algorithms. The paramphistomes displayed the typical four helix ITS2 secondary structure and differed from each other due to minor nucleotide differences. The consensus ITS2 secondary structure model revealed the presence of conservative motifs GACGAGGGUG and GCGGUAGAGUC in helix III. Monophyly is well supported for a clade consisting of the Japanese and Indian paramphistomes with significant bootstrap values.


MRI combined with MR cholangiopancreatography versus helical CT in the evaluation of patients with suspected periampullary tumors: a prospective comparative study.
To establish the diagnostic accuracy of MRI including MR cholangiopancreatography (MRCP) compared with helical CT in the differentiation of malignant and benign lesions in the periampullary region. Fifty-one patients (27 M, 24 F, mean age 66 years, range 39-86 years) with obstructive jaundice and sonographic evidence of intra- and extrahepatic bile duct dilatation (n=31) or suspicion of periampullary tumor, based on previously performed ultrasound and/or CT examination (n=20), were studied. MRI with MRCP and helical CT were reviewed blindly under standardized conditions. Lesion status (differentiation of malignant versus benign) was rated on a 5-point diagnostic confidence scale. Reference standards for comparison were findings at surgery or laparoscopy and/ or the clinical outcome. The predictive value of imaging findings was determined with multivariate logistic regression analysis. The areas under the receiver operating characteristic curve were 0.96 for MRI with MRCP and 0.81 for CT (P <0.05). Multivariate analysis of eight imaging variables at MRI indicated that a stricture with malignant characteristics at MRCP was the best predictor of malignancy. MRI with MRCP was significantly more accurate than CT in differentiating between malignant and benign lesions in patients with suspected periampullary tumors, mainly due to the information obtained on the MRCP images of the biliary and pancreatic duct anatomy.


Fast 3D reconstruction of the spine from biplanar radiographs using a deformable articulated model.
This paper proposes a novel method for fast 3D reconstructions of the scoliotic spine from two planar radiographs. The method uses a statistical model of the shape of the spine for computing the 3D reconstruction that best matches the user input (about 7 control points per radiograph). In addition, the spine was modelled as an articulated structure to take advantage of the dependencies between adjacent vertebrae in terms of location, orientation and shape. The accuracy of the method was assessed for a total of 30 patients with mild to severe scoliosis (Cobb angle [22°, 70°]) by comparison with a previous validated method. Reconstruction time was 90 s for mild patients, and 110 s for severe. Results show an accuracy of ∼0.5mm locating vertebrae, while orientation accuracy was up to 1.5° for all except axial rotation (3.3° on moderate and 4.4° on severe cases). Clinical indices presented no significant differences to the reference method (Wilcoxon test, p ≤ 0.05) on patients with moderate scoliosis. Significant differences were found for two of the five indices (p=0.03) on the severe cases, while errors remain within the inter-observer variability of the reference method. Comparison with state-of-the-art methods shows that the method proposed here generally achieves superior accuracy while requiring less reconstruction time, making it especially appealing for clinical routine use.


Comparison of ultrasensitive and mass spectrometry quantification of blood-based amyloid biomarkers for Alzheimer's disease diagnosis in a memory clinic cohort.
Alzheimer's disease (AD) is a complex neurodegenerative disorder with β-amyloid pathology as a key underlying process. The relevance of cerebrospinal fluid (CSF) and brain imaging biomarkers is validated in clinical practice for early diagnosis. Yet, their cost and perceived invasiveness are a limitation for large-scale implementation. Based on positive amyloid profiles, blood-based biomarkers should allow to detect people at risk for AD and to monitor patients under therapeutics strategies. Thanks to the recent development of innovative proteomic tools, the sensibility and specificity of blood biomarkers have been considerably improved. However, their diagnosis and prognosis relevance for daily clinical practice is still incomplete. The Plasmaboost study included 184 participants from the Montpellier's hospital NeuroCognition Biobank with AD (n = 73), mild cognitive impairments (MCI) (n = 32), subjective cognitive impairments (SCI) (n = 12), other neurodegenerative diseases (NDD) (n = 31), and other neurological disorders (OND) (n = 36). Dosage of β-amyloid biomarkers was performed on plasma samples using immunoprecipitation-mass spectrometry (IPMS) developed by Shimadzu (IPMS-Shim Aβ42, Aβ40, APP669-711) and Simoa Human Neurology 3-PLEX A assay (Aβ42, Aβ40, t-tau). Links between those biomarkers and demographical and clinical data and CSF AD biomarkers were investigated. Performances of the two technologies to discriminate clinically or biologically based (using the AT(N) framework) diagnosis of AD were compared using receiver operating characteristic (ROC) analyses. The amyloid IPMS-Shim composite biomarker (combining APP669-711/Aβ42 and Aβ40/Aβ42 ratios) discriminated AD from SCI (AUC: 0.91), OND (0.89), and NDD (0.81). The IPMS-Shim Aβ42/40 ratio also discriminated AD from MCI (0.78). IPMS-Shim biomarkers have similar relevance to discriminate between amyloid-positive and amyloid-negative individuals (0.73 and 0.76 respectively) and A-T-N-/A+T+N+ profiles (0.83 and 0.85). Performances of the Simoa 3-PLEX Aβ42/40 ratio were more modest. Pilot longitudinal analysis on the progression of plasma biomarkers indicates that IPMS-Shim can detect the decrease in plasma Aβ42 that is specific to AD patients. Our study confirms the potential usefulness of amyloid plasma biomarkers, especially the IPMS-Shim technology, as a screening tool for early AD patients.


Migration of localizing wires used in guided biopsy of the breast.
Inadvertent retraction of a localizing wire into the breast occurred in three of a series of 158 localizations prior to biopsy for an impalpable mammographic abnormality. In each case retraction was followed by migration into the subcutaneous tissues and/or spontaneous extrusion. A wire inserted for localization prior to guided biopsy of the breast should be left long and secured externally to prevent retraction.


Capillary zone electrophoresis-based cytotoxicity analysis of Caco-2 cells.
A capillary zone electrophoresis-based method to evaluate the cytotoxicity of substances to Caco-2 cells was established. The estimation of the injected cell number (500-5000) and the minor effect of injection condition on cytotoxicity determination were investigated. Caco-2 cells the best model of the intestinal absorptive epithelium, were treated with substances and then stained with Trypan Blue and fixed with paraformaldehyde. The treated Caco-2 cells were detected simultaneously at 590 nm and 214 nm, and the absorbance ratio of the two wavelengths (R(590/214)) can reflect simultaneously the loss of cell membrane integrity and the degradation/leak of intracellular components and indicate the cytotoxicity of substances. The cytotoxicity of the four substances sodium sulfite (Na(2)SO(3)), methyl mercury (MeHg), paclitaxel (PTX), and cadmium chloride (CdCl(2)) were determined and compared. There was no obvious cytotoxicity caused by 20 μM Na(2)SO(3) for 24 h treatment, and the toxicity of the other three toxicants was sequenced as: CdCl(2) > MeHg > PTX. The results are in good agreement with the references and the conventional Trypan Blue exclusion counting assay.


Genome-wide identification and expression profiles of the Phytophthora infestans responsive CYPome (Cytochrome P450 complement) in Solanum tuberosum.
Cytochrome P450s represent one of the largest protein families across all domains of life. In plants, biotic stress can regulate the expression of some P450 genes. However, the CYPome (cytochrome P450 complement) in Solanum tuberosum and its response to Phytophthora infestans infection remains unrevealed. In this study, 488 P450 genes were identified from potato genome, which can be divided into 41 families and 57 subfamilies. Responding to the infection of P. infestans, 375 potato P450 genes were expressed in late blight resistant or susceptible cultivars. A total of 14 P450 genes were identified as resistant related candidates, and 81 P450 genes were identified as late blight responsive candidates. Several phytohormone biosynthesis, brassinosteroid biosynthesis, and phenylpropanoid biosynthesis involved P450 genes were differentially expressed during the potato-pathogen interactions. This study firstly reported the CYPome in S. tuberosum, and characterized the expression patterns of these P450 genes during the infection of P. infestans.


8-hydroxyguanine (7,8-dihydro-8-oxoguanine) DNA glycosylase and AP lyase activities of hOGG1 protein and their substrate specificity.
Recently we cloned a structural human homolog (hOGG1) of the yeast OGG1 (yOGG1) gene that is involved in the excision repair of 8-hydroxyguanine (also known as 7,8-dihydro-8-oxoguanine; oh8Gua), hOGG1 protein shares 38% amino acid identity with yOGG1 protein. In this paper, we define the substrate specificity of oh8Gua DNA glycosylase and AP lyase activities of the hOGG1 protein. The oh8Gua released from oh8Gua containing DNA was measured by analysis with HPLC coupled with electrochemical detector (ECD) and cleavage sites in the DNA were identified by cleavage assay using gel electrophoresis. GST-hOGG1 protein possessed the oh8Gua DNA glycosylase/AP lyase activity and weak delta-elimination activity, oh8Gua opposite the C in duplex oligonucleotide was most efficiently released by GST-hOGG1 protein and oh8Gua opposite the T was also released, while oh8Gua opposite the G or A was very slowly done. The rank order of DNA cleavage efficiency was the same as that of oh8Gua glycosylase activity. Glycosylase/AP lyase activities and their substrate specificities of the GST-hOGG1 protein was similar to GST-yOGG1 protein but different from MutM protein. These results indicate that the dominant function of hOGG1 protein is a oh8Gua glycosylase reaction by specifically recognizing oh8Gua and pyrimidine opposite the oh8Gua and delta-elimination reaction in the same manner as yOGG1 protein. Thus, the hOGG1 gene is a functional human homolog of the yOGG1 gene on oh8Gua excision repair in spite of the low structural identity at amino acid level between hOGG1 and yOGG1 proteins.


Fatty acyl-CoA dehydrogenase enzymes in human skeletal muscle.
An electrophoretic and enzyme-substrate staining technique for acyl-CoA dehydrogenase (ACD) enzymes was developed for use with small (less than 100 mg) tissue samples. Based on their electrophoretic mobility and substrate staining specificity, at least two and perhaps three chain-length specific enzymes for dehydrogenation of saturated fatty acids were found in human skeletal muscle. ACD enzymes staining with octanoyl-CoA or palmitoyl-CoA were identified by this technique in human skeletal muscle, heart, and liver, but the ACD enzyme staining with butyryl-CoA was difficult to detect and was definitely visualized only in skeletal muscle.


Scalable in situ single-cell profiling by electrophoretic capture of mRNA using EEL FISH.
Methods to spatially profile the transcriptome are dominated by a trade-off between resolution and throughput. Here we develop a method named Enhanced ELectric Fluorescence in situ Hybridization (EEL FISH) that can rapidly process large tissue samples without compromising spatial resolution. By electrophoretically transferring RNA from a tissue section onto a capture surface, EEL speeds up data acquisition by reducing the amount of imaging needed, while ensuring that RNA molecules move straight down toward the surface, preserving single-cell resolution. We apply EEL on eight entire sagittal sections of the mouse brain and measure the expression patterns of up to 440 genes to reveal complex tissue organization. Moreover, EEL can be used to study challenging human samples by removing autofluorescent lipofuscin, enabling the spatial transcriptome of the human visual cortex to be visualized. We provide full hardware specifications, all protocols and complete software for instrument control, image processing, data analysis and visualization.


Pelvic exenteration for recurrent or advanced gynecologic malignancies - Analysis of outcome and complications.
Pelvic exenterations are known to be a last resort therapeutic option for advanced or recurrent gynecologic malignancies, which are known to have poor prognosis. All women treated with anterior (APE) or total (TPE) pelvic exenteration at our University hospital within a five-year period were identified and their data retrospectively analysed. Parameters such as demographic information, tumor type and stage, previous therapy as well as complication rate and overall survival were evaluated. 47 women were enrolled in this study. Most common indication for PE was cervical cancer (51.1%) followed by carcinoma of the vagina (17%), vulva (10.6%), endometrium (8.5%), ovaries (4.3%) and uterus (2.1%). Patients had received 1, 2 or 3 treatment modalities prior in 12.8%, 38.8% and 21.2% respectively. Predominant urinary diversion was ileum conduit (75.5%). Major complications (Clavien Dindo ≥ III) were observed in 40.4%, none in 19.2%. Early mortality was 4.3%. Median Overall Survival (mOS) was 14 months with 2- and 3-year survival rates of 38.8% and 21.2% respectively. After a median follow up of 47 months, 25.5% were still alive. Excluding patients with metastatic disease (n = 10), mOS was 20.6 months with 2- and 3-year survival rates of 46% and 35.2%. OS was significantly worse for patients with positive margins (p = 0.003). Receiving neoadjuvant treatment (25.5%) correlated with negative margins (p = 0.013) but not with overall survival. PE is feasible with acceptable complication and mortality rates. The long-time benefit is notable bearing in mind the extensive nature of the malignancies and the procedure undertaken.


Pd(II)-Catalyzed tandem selective dehydrogenative [4+2] annulation of 2-methyl-1,3-cycloalkanediones with olefins.
A practical and effective palladium-catalyzed selective dehydrogenative [4+2] annulation of 2-methyl-1,3-cycloalkanediones with olefins was reported. The active 2-methylene-1,3-cycloalkanedione was in situ generated via Pd-catalyzed enolate oxidation processes, and it subsequently reacted with a wide variety of olefins to afford various polysubstituted dihydropyran derivatives in good to excellent yields.


Current status of the treatment of degenerative mitral valve regurgitation.
Degenerative mitral valve disease (myxomatous degeneration or fibroelastic deficiency) is the most common indication for surgical referral to treat mitral regurgitation. Mitral valve repair is the procedure of choice whenever feasible and when the results are expected to be durable. Posterior leaflet prolapse is the commonest lesion, found in up to two-thirds of patients. It is the easiest to repair, particularly when limited to one segment. In these cases, rates of repairability and procedural success approach 100%, and there is now ample evidence that the immediate and long-term results are better than those of valve replacement. Notably, minimally invasive valvular procedures, surgical or interventional, have attracted increasing interest in the last decade. When performed by experienced groups, mitral valve repair is unrivaled irrespective of the severity of lesions, from simple to complex, which leaflets are involved, and the type of degenerative involvement (myxomatous or fibroelastic). Its results should be viewed as the benchmark for other present and future technologies. By contrast, percutaneous mitral valve repair is still in its infancy and its results so far fall short of those of surgical repair. Nevertheless, continued investment in transcatheter procedures is of great importance to enable development and improved accessibility, particularly for patients who are considered unsuitable for surgery. In this review, we analyze the current status of management of degenerative mitral valve disease, discussing mitral valve anatomy and pathology, indications for intervention, and current surgical and transcatheter mitral valve procedures and results.


Prognostic significance of miR-122 expression after curative resection in patients with hepatocellular carcinoma.
Downregulation of MicroRNA-122 (miR-122) and its association with cancer progression have been reported in hepatocellular carcinoma (HCC) cell line models and a limited number of HCC samples. Recently, restoration of miR-122 expression by direct delivery of miR-122 yielded promising results in HCCs. However, the prognostic effect of miR-122 expression in human HCC samples is not fully understood. We investigated the expression level of miR-122 by quantitative real-time polymerase chain reaction in 289 curatively resected HCC samples and 20 normal liver samples and evaluated the prognostic effect of miR-122 expression. The relative quantification value of miR-122 was much lower in HCC samples than in normal liver tissues. During a median 119 months of follow-up for survival, the low miR-122 expression group showed shorter recurrence-free survival (RFS) (p = 0.033) and intrahepatic recurrence-free survival (IHRFS) (p = 0.014), and a trend of short distant metastasis-free survival (DMFS) (p = 0.149) than high expression group. On multivariate analysis, miR-122 expression was an independent prognostic factor for RFS, IHRFS and DMFS. Downregulation of miR-122 expression, frequently found in HCC samples, was an independent prognostic factor for RFS after curative resection. Emerging therapeutic approaches targeting miR-122 could be applicable in patients with miR-122 downregulated hepatocellular carcinoma.


Factors predictive of Crohn disease following colectomy in medically refractory pediatric colitis.
Crohn disease (CD) has been diagnosed following colectomy for ulcerative colitis (UC). This study aims to determine the frequency of this occurrence, and to identify predictive factors leading to a CD diagnosis. A retrospective chart review was performed in patients who have undergone colectomy. From 1996 to 2006, colectomy was performed in 212 patients, 37 of whom were diagnosed preoperatively with UC. The mean ages at diagnosis and at colectomy were 10.6+/-4.3 years and 13.7+/-3.7 years, respectively. Inflammatory bowel disease serology at diagnosis in 29 patients showed that 26 (90%) were pANCA+. Serology was negative in 3. Ten (27%) had nonspecific inflammation of the upper digestive tract. Radiographs in 25 patients indicated no abnormalities in the small intestine. Before colectomy, patients (n=35) were treated with corticosteroid (97%), 5-ASA (69%), immunomodulator (66%), infliximab (29%), and cyclosporin (11%). The mean postoperative follow-up was 2.6+/-2 years. Six patients (16%) were found to have CD. All 6 patients were pANCA+ with elevated anti-OmpC (n=4), ASCA immunoglobulin A (n=2), and ASCA immunoglobulin G (n=1). The CD group had higher mean anti-OmpC compared with the UC group, 16.9+/-5.2 and 6.2+/-3.4, respectively (P<0.005). Weight z score at time of surgery was lower in the CD group (-1.38+/-0.79) than in the UC group (0.29+/-0.24), P<0.05. The possibility of CD remains in a small fraction of patients who undergo colectomy for medically refractory UC. A lower weight and a higher anti-OmpC titer may be predictive of CD.


Radiographers' assessment of referrals for CT and MR imaging using a web-based data collection tool.
There is limited research related to the radiographers' role in assessing of radiology referrals to justify imaging. This study investigated radiographers' compliance with guidelines in the assessment of CT and MRI referrals and factors that influenced their performance. This research was facilitated by the EFRS Research Hub at ECR 2019. Five radiology referral scenarios for CT and/or MRI were distributed to radiographers, as determined by their scope of practice, who volunteered at the Research Hub. A web-based data collection tool was used. The radiographers were required to determine the appropriateness of each referral, highlight any concerns and recommend suitable investigations if applicable. Linear regression analysis was used to determine whether postgraduate qualification, grade/role of the radiographer and use of guidelines influenced the radiographers' performance in assessing the referrals. Participants originated from 24 countries (n = 51 CT, n = 40 MRI), the majority originating from the UK, Ireland, Italy, Spain, Norway and Austria. Responses consistent with guidelines were 58% and 57% for CT and MRI, respectively. Possession of an MSc qualification in CT was a significant factor of influence for a higher consistency with guidelines (p = 0.02) in CT. Employment as a radiographer in a lead professional role and/or educator was a significant factor of influence for a higher consistency with guidelines in MRI (p = 0.01). A total of 58% for CT and 57% for MRI of the radiographers' responses complied with guidelines. Factors such as postgraduate education and leading professional roles are associated with better performance. Considering qualifications, experience and managerial role is vital before radiographers are delegated task of justifying CT and MR Imaging.


RNA-seq analysis of gene expression changes in cuticles during the larval-pupal metamorphosis of Plutella xylostella.
The diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae) is a holometabolous insect that its cuticles must undergo the significant changes during the larval-pupal metamorphosis development. To elucidate these changes at molecular levels, RNA-seq analysis of cuticles from LLS (later fourth instar larval stage), PPS (prepupal stage) and PS (pupal stage) were performed in P. xylostella. In this paper, a total of 17,710 transcripts were obtained in the larval-pupal transition of P. xylostella, and out of which 2293 (881 up-regulated and 1412 down-regulated) and 2989 transcripts (2062 up-regulated and 927 down-regulated) were identified to be differentially expressed between LLS and PPS, as well as PPS and PS, respectively. The further GO and KEGG analysis of differentially expressed genes (DEGs) revealed that the 'structural constituent of cuticle', 'chitin metabolic process', 'chitin binding', 'tyrosine metabolism' and 'insect hormone biosynthesis' pathways were significantly enriched, indicating these pathways might be involved in the process of larval pupation in P. xylostella. Then, we found some genes that encoded cuticular proteins, chitinolytic enzymes, chitin synthesis enzymes, and cuticle tanning proteins changed their expression levels remarkably, indicating these genes might play important roles in the restruction (degradation and biosynthesis) of insect cuticles during the larval metamorphosis. Additionally, the significant changes in the mRNA levels of 20-hydroxyecdysone (20E) and juvenile hormone (JH) related genes suggested their crucial roles in regulating cuticle remodeling during the larval metamorphosis of P. xylostella. In conclusion, the present study provide us the comprehensive gene expression profiles to explore the molecular mechanisms of cuticle metamorphosis in P. xylostella, which laid a molecular basis to study roles of specific pathways and genes in insect development.


A partial least squares analysis of seizure outcomes following resective surgery for tuberous sclerosis complex in children with intractable epilepsy.
Previous studies aimed at identifying predictors of seizure outcomes following resective surgery for tuberous sclerosis complex (TSC) are limited by multicollinearity among predictors, whereby the high degree of correlation between covariates precludes detection of potentially significant findings. Here, we apply a data-driven method, partial least squares (PLS) to model multidimensional variance and study significant patterns in data that are associated with seizure outcomes. Post hoc analysis of 186 children with TSC who underwent resective epilepsy surgery derived from an individual participant data meta-analysis was performed. PLS was used to derive a latent variable (component) that relates clinical covariates with Engel classification. Permutation testing was performed to evaluate the significance of the component, and bootstrapping was used to identify significant contributors to the component. A significant component was identified, which represents the pattern of covariates related to Engel class. The strongest and significant factors contributing to this component were focal ictal electroencephalogram and concordance of electroencephalography (EEG)-magnetic resonance imaging (MRI) abnormality. Interestingly, covariates contributing the least to the seizure-free patient phenotype were continent of treatment and age at the time of surgery. Using a data-driven, multivariate method, PLS, we describe patient phenotypes that are associated with seizure-freedom following resective surgery for TSC.


Association between statin use and the risks of glaucoma in Australia: a 10-year cohort study.
In a cohort of middle-aged and elderly Australians, we found that long-term statin use was associated with a higher risk of glaucoma onset. As to subtypes of statins, the increased risk was only found in rosuvastatin users. To investigate the relationship between statin use and glaucoma onset in a 10-year longitudinal study. This nested case-control study was based on data from a large-scale cohort of Australians aged over 45 years old. Medication exposure was identified by claims records from the Pharmaceutical Benefits Scheme during the follow-up period (2009-2016). The onset of glaucoma was defined as the people with at least three claims of antiglaucoma medications. Controls matched by age, gender and cardiovascular diseases were selected from participants without prescription of antiglaucoma medications. A conditional logistic regression model was used to assess the association between statin use and glaucoma onset. The proportion of statin users was higher in the case group (40.5%) than that in the control group (38.4%). After adjusting for baseline characteristics and longitudinal claims records, statin use was not associated with glaucoma onset (OR 1.04, 95% CI 0.97 to 1.11). However, an increased risk of glaucoma onset was observed in participants with a longer duration of statin use (>3 years vs <1 year: OR 1.12, 95% CI 1.04 to 1.21). With respect to specific types of statins, participants taking rosuvastatin were more likely to suffer from glaucoma (OR 1.11, 95%CI 1.01 to 1.22). The use of other statins was not significantly associated with glaucoma onset. Long-term statin use was found to be associated with a higher risk of glaucoma onset in this study. Regarding specific types of statins, the increased risk of glaucoma onset was only observed in users of rosuvastatin.


Evaluation of nutritional composition and antioxidant properties of underutilized Ficus talboti King fruit for nutraceuticals and food supplements.
This study investigated change in the chemical components and antioxidant activity of Ficus talboti fruit for the development of functional foods. Proximate compositions of crude protein, ash and fat were 23.28, 10.47 and 3.86% respectively. Macro-nutrient contents were found to be higher in the fruit when compared to micronutrients. The analysis also showed the presence of almost all the essential and non-essential amino acids especially Leucine, Phenylalanine and tyrosine in higher amount. Linolenic acid content was higher than stearic acid among the fatty acids in the fruit. Total phenolic content (35.4 ± 0.32 g GAE /100 g) was found in higher amount in acetone extract. The IC50 values of 1,1-diphenyl-2-picrylhydrazyl, hydroxyl and superoxide radical scavenging of acetone extract were 346, 252 and 652 μg/mL respectively. Thus, F. talboti fruit can be used as a healthy and functional food ingredient which will ensure dietary diversity and food security among the marginalized and poor communities.


Nomogram based on pretreatment hepatic and renal function indicators for survival prediction of locally advanced esophageal squamous cell carcinoma with treatment of neoadjuvant chemoradiotherapy plus surgery.
The parameters for survival prediction of esophageal squamous cell carcinoma (ESCC) patients treated with neoadjuvant chemoradiotherapy (NCRT) combined with surgery are unclear. Here, we aimed to construct a nomogram for survival prediction of ESCC patients treated with NCRT combined with surgery based on pretreatment serological hepatic and renal function tests. A total of 174 patients diagnosed as ESCC were enrolled as a training cohort from July 2007 to June 2019, and approximately 50% of the cases (n = 88) were randomly selected as an internal validation cohort. Univariate and multivariate Cox survival analyses were performed to identify independent prognostic factors to establish a nomogram. Predictive accuracy of the nomogram was evaluated by Harrell's concordance index (C-index) and calibration curve. ALT, ALP, TBA, TP, AST, TBIL and CREA were identified as independent prognostic factors and incorporated into the construction of the hepatic and renal function test nomogram (HRFTNomogram). The C-index of the HRFTNomogram for overall survival (OS) was 0.764 (95% CI 0.701-0.827) in the training cohort, which was higher than that of the TNM staging system (0.507 (95% CI 0.429-0.585), P < 0.001). The 5-year OS calibration curve of the training cohort demonstrated that the predictive accuracy of the HRFTNomogram was satisfactory. Moreover, patients in the high-risk group stratified by the HRFTNomogram had poorer 5-year OS than those in the low-risk group in the training cohort (27.4% vs. 80.3%, P < 0.001). Similar results were observed in the internal validation cohort. A novel HRFTNomogram might help predict the survival of locally advanced ESCC patients treated with NCRT followed by esophagectomy.


Paracrine-like excitation of low-threshold mechanoceptive C-fibers innervating rat hairy skin is mediated by substance P via NK-1 receptors.
We reported previously that C-fibers innervating rat skin can be excited by short trains of electrical shocks ('tetanus') applied to neighboring nerves. Since these nerves were disconnected from the CNS, the cross-talk is located peripherally. Here we tested if low-threshold mechanoceptive (LTM) C-fibers can be excited by this cross-talk and if this process is mediated by substance P (SP) via neurokinin-1 (NK-1) receptors. In urethane anesthetized rats we found that 80% (56/71) of LTM C-fibers, recorded in the lateral cutaneous branch of the dorsal ramus (CBDR) of T10 spinal nerve, were excited by a 10s, 20 Hz tetanus of the T9 CBDR. Compared to the spontaneous pre-tetanic firing frequency of 1.62+/-0.40 impulses/30s, the frequency significantly increased to 3.74+/-0.99, 3.17+/-0.69 and 2.92+/-0.63 impulses/30s, at 30, 60 and 90 s after the tetanus, respectively, and declined to the baseline frequency thereafter. When injected into their receptive fields, SP mimicked the tetanically induced increase of firing rate, whereas the NK-1 receptor antagonist WIN 51708 blocked the excitation in most fibers. The excitation was significantly diminished in adult rats that were neonatally treated with capsaicin, a treatment that destroys most SP-expressing afferent fibers. Thus, we conclude that peptidergic primary afferents are functionally linked with adjacent LTM C-fibers in a non-synaptic, paracrine-like signaling pathway via SP and NK-1 receptors, and perhaps also other agents as well. We propose that this cross-talk has evolved as a mechanism regulating the mechanoceptive characteristics of LTM C-fibers, presumably contributing to pain sensation elicited by tactile stimuli ('allodynia').


Difficulty in diagnosing mild cases of COVID-19 without respiratory symptoms during the Novel Coronavirus Pandemic: Careful monitoring needed for patients with persistent upper gastrointestinal symptoms.
Gastrointestinal symptoms have been reported to occur with COVID infection, and clinicians in COVID-19-endemic areas should suspect COVID-19 infection in patients even if they have no noticeable respiratory symptoms and only gastrointestinal symptoms.


Spinal cord stimulation modulates activity of lumbosacral spinal neurons receiving input from urinary bladder in rats.
The aim of this study was to determine whether spinal cord stimulation (SCS) modulates activity of lumbosacral spinal neurons receiving input from the urinary bladder. Extracellular potentials of L6-S2 spinal neurons were recorded in pentobarbital anesthetized, paralyzed and ventilated male rats. SCS (50 Hz, 0.2 ms, 3-5 min, 90% motor threshold) was applied on the dorsal column of L2-L3 and C1-C2 segments and significantly reduced excitatory responses of 18/25 (72%) and 13/19 (68%) lumbosacral neurons to noxious urinary bladder distension (UBD, > or =1.0 ml, 20 s), respectively. SCS affected spinal neurons with either high- or low-threshold responses to UBD. These results suggested that SCS might have a potential therapeutic effect for patients with hypersensitivity and/or pain of cystitis and other urinary bladder disorders.


Placental-type alkaline phosphatase in peritoneal fluid of women with endometriosis.
Alkaline phosphatase (ALP) activities were studied in peritoneal fluid obtained from patients with untreated endometriosis and control women who had normal pelves. The patients (n = 18) had significantly higher total ALP (8.65 +/- 5.69 mU/mg, p less than 0.01) and thermostable ALP (0.28 +/- 0.23 mU/mg, p less than 0.05) than the controls (n = 7) (total ALP = 2.41 +/- 1.15; thermostable ALP = 0.09 +/- 0.04 mU/mg). The contents of the thermostable ALP in the total ALP were 4.5 +/- 2.4% for controls and 3.6 +/- 2.3% for patients. To define the biochemical characteristics of the thermostable ALP, the enzyme was partially purified from a mixture of peritoneal fluid from 16 patients. The partially purified, heated ALP (PFALP) responded to the various inhibitors, activators, and pH values tested in a significantly similar manner as a purified, heated human placental ALP did. Our data suggest that PFALP may be a placental-type (or Regan) ALP.


Diagnostic value of hemosiderin-containing macrophages in bronchoalveolar lavage.
Our objective was to determine if the hemosiderin content of BAL macrophages allows us to draw any differential diagnostic conclusions in a variety of lung diseases. One hundred one patients who underwent BAL for different diagnostic reasons were studied prospectively. The highest values for the hemosiderin score (HS) were found in patients with active alveolar hemorrhage and patients who had undergone heart transplantation for congestive heart failure. Compared to a control population, patients with Pneumocystis carinii pneumonia or invasive aspergillosis had a higher HS than patients with bacterial pneumonia or mycobacterial lung infection. High or intermediate values for HS were more often found in patients with a low than in those with a normal platelet count. The differential diagnostic conclusions which can be based on an HS are limited.