Dynamics of the COVID -19 Related Publications

BackgroundThis study aims to analyze the dynamics of the published articles and preprints of Covid-19 related literature from different scientific databases and sharing platforms. MethodsThe PubMed, Elsevier, and Research Gate (RG) databases were under consideration in this study over a specific time. Analyses were carried out on the number of publications as (a) function of time (day), (b) journals and (c) authors. Doubling time of the number of publications was analyzed for PubMed "all articles" and Elsevier published articles. Analyzed databases were (1A) PubMed "all articles" (01/12/2019-12/06/2020) (1B) PubMed Review articles (01/12/2019-2/5/2020) and (1C) PubMed Clinical Trials (01/01/2020-30/06/2020) (2) Elsevier all publications (01/12/2019-25/05/2020) (3) RG (Article, Pre Print, Technical Report) (15/04/2020-30/4/2020). FindingsTotal publications in the observation period for PubMed, Elsevier, and RG were 23000, 5898 and 5393 respectively. The average number of publications/day for PubMed, Elsevier and RG were 70.0 {+/-}128.6, 77.6{+/-}125.3 and 255.6{+/-}205.8 respectively. PubMed shows an avalanche in the number of publication around May 10, number of publications jumped from 6.0{+/-}8.4/day to 282.5{+/-}110.3/day. The average doubling time for PubMed, Elsevier, and RG was 10.3{+/-}4 days, 20.6 days, and 2.3{+/-}2.0 days respectively. In PubMed average articles/journal was 5.2{+/-}10.3 and top 20 authors representing 935 articles are of Chinese descent. The average number of publications per author for PubMed, Elsevier, and RG was 1.2{+/-}1.4, 1.3{+/-}0.9, and 1.1{+/-}0.4 respectively. Subgroup analysis, PubMed review articles mean and median review time for each article were <0|17{+/-}17|77> and 13.9 days respectively; and reducing at a rate of-0.21 days (count)/day. InterpretationAlthough the disease has been known for around 6 months, the number of publications related to the Covid-19 until now is huge and growing very fast with time. It is essential to rationalize the publications scientifically by the researchers, authors, reviewers, and publishing houses. FundingNone

Mutations in SUFU and PTCH1 genes may cause different cutaneous cancer predisposition syndromes: similar, but not the same.

Many cancer predisposition syndromes are preceded or accompanied by a range of typical skin signs. Gorlin syndrome is a rare multisystem inherited disorder which can predispose to basal cell carcinomas (BCCs), childhood medulloblastomas in addition to various developmental abnormalities; the majority of cases are due to mutations in the PTCH1 gene. Approximately 5% of cases have been attributed to a mutation in the SUFU gene. Certain phenotypic features have been identified as being more prevalent in individuals with a SUFU mutation such as childhood medulloblastoma, infundibulocystic BCCs and trichoepitheliomas. Recently hamartomatous skin lesions have also been noted in families with childhood medulloblastoma, a "Gorlin like" phenotype and a SUFU mutation. Here we describe a family previously diagnosed with Gorlin syndrome with a novel SUFU splice site deleterious genetic variant, who have several dermatological features including palmar sclerotic fibromas which has not been described in relation to a SUFU mutation before. We highlight the features more prominent in individuals with a SUFU mutation. It is important to note that emerging therapies for treatment of BCCs in patients with a PTCH1 mutation may not be effective in those with a SUFU mutation.

A Multialgorithm Approach to Land Surface Modeling of Suspended Sediment in the Colorado Front Range.

A new paradigm of simulating suspended sediment load (SSL) with a Land Surface Model (LSM) is presented here. Five erosion and SSL algorithms were applied within a common LSM framework to quantify uncertainties and evaluate predictability in two steep, forested catchments (>1,000 km2). The algorithms were chosen from among widely used sediment models, including empirically based: monovariate rating curve (MRC) and the Modified Universal Soil Loss Equation (MUSLE); stochastically based: the Load Estimator (LOADEST); conceptually based: the Hydrologic Simulation Program-Fortran (HSPF); and physically based: the Distributed Hydrology Soil Vegetation Model (DHSVM). The algorithms were driven by the hydrologic fluxes and meteorological inputs generated from the Variable Infiltration Capacity (VIC) LSM. A multiobjective calibration was applied to each algorithm and optimized parameter sets were validated over an excluded period, as well as in a transfer experiment to a nearby catchment to explore parameter robustness. Algorithm performance showed consistent decreases when parameter sets were applied to periods with greatly differing SSL variability relative to the calibration period. Of interest was a joint calibration of all sediment algorithm and streamflow parameters simultaneously, from which trade-offs between streamflow performance and partitioning of runoff and base flow to optimize SSL timing were noted, decreasing the flexibility and robustness of the streamflow to adapt to different time periods. Parameter transferability to another catchment was most successful in more process-oriented algorithms, the HSPF and the DHSVM. This first-of-its-kind multialgorithm sediment scheme offers a unique capability to portray acute episodic loading while quantifying trade-offs and uncertainties across a range of algorithm structures.

Assessment of phagocytic activity of neutrophils in chronic obstructive pulmonary disease.

AIM: To assess the phagocytic activity of neutrophils in subjects with chronic obstructive pulmonary disease (COPD). BACKGROUND/NEED OF STUDY: There is a paucity of data in relation to phagocytic function in COPD. By this multidisciplinary study, a better understanding about the etiology of lung destruction among COPD patients is being sought. MATERIALS AND METHODS: The study was conducted among 28 subjects with COPD and 25 controls in a private tertiary hospital in Chennai after obtaining Institutional Ethical Clearance. Known cases of COPD as proven by clinical findings and spirometry were included in the study, and subjects with any other source of infection, recent surgery, or chronic granulomatous disease were excluded. The study subjects were divided into three groups based on the severity of COPD as determined by spirometry, and healthy volunteers were taken as Group 4. After obtaining informed consent, validated respiratory health questionnaire was administered. The phagocytic function was assessed by Candida phagocytic test and Nitroblue Tetrazolium (NBT) Reduction Test. RESULTS: Significantly impaired phagocytic function as indicated by lower phagocytic, lytic indices and decreased NBT reduction of neutrophils was seen in COPD subjects compared to normal healthy controls (P < .001). CONCLUSION: This study showed that there is phagocytic dysfunction in COPD subjects when compared with normal subjects. This could be due to underlying inflammation in human airway. Understanding the role of neutrophils may lead to improved understanding of the pathogenesis of COPD, which in turn may pave way for implementing modified therapeutic intervention strategies.

Effects of carnitine supplementation on muscle metabolism by the use of magnetic resonance spectroscopy and near-infrared spectroscopy in end-stage renal disease.

BACKGROUND/AIM: A defect in skeletal muscle mitochondrial metabolism develops in patients with chronic renal failure on haemodialysis. Treatment with carnitine, a compound essential for normal mitochondrial function, has been suggested to have significant benefits in such patients, so we carried out a study to see if carnitine acts by improving muscle bioenergetics and function. METHODS: In a phase II randomised double-blind trial, patients with end-stage renal disease received placebo or intravenous L-carnitine (20 mg/kg dry body weight three times weekly after haemodialysis) for 16 weeks (n = 13 in each group). 31P magnetic resonance spectroscopy, 1H magnetic resonance imaging and near-infrared spectroscopy were used to measure muscle bioenergetics and function at baseline and at 16 weeks. RESULTS: There were no significant differences between groups at baseline. Mean plasma carnitine rose 10-fold in the carnitine group but was unchanged in the placebo group. L-carnitine had no statistically significant effect on any of the parameters measured. The rate of proton efflux from muscle, as a measure of tissue perfusion, was low in both groups and was not affected by treatment. CONCLUSIONS: The study failed to show any significant effect of 16 weeks' L-carnitine supplementation on these objective measures of muscle metabolism and function. Slow proton efflux from muscle provides evidence supporting low blood flow and, therefore, decreased oxygen availability, as an underlying mechanism for muscle mitochondrial dysfunction in this disorder.

Quantitative proton magnetic resonance spectroscopy of the cervical spinal cord.

Proton MR spectroscopy ((1)H-MRS) provides indices of neuronal damage in the central nervous system (CNS); however, it has not been extensively applied in the spinal cord. This work describes an optimized proton spectroscopy protocol for examination of the human cervical spinal cord. B(0) field mapping of the cord revealed periodic inhomogeneities due to susceptibility differences with surrounding tissue. By combining field maps and experimental data, we found that the optimum voxel size was 9 x 7 x 35 mm(3) placed with the inferior end of the voxel above vertebral body C2. Metabolite concentrations were determined in the cervical cord in six healthy controls by short-echo point-resolved spectroscopy (PRESS) volume localization. The results were compared with metabolite concentrations in the brainstem, cerebellum, and cortex in the same individuals. The concentrations in the cervical cord were as follows: N-acetyl-aspartate (NAA) 17.3 +/- 0.5, creatine (Cr) 9.5 +/- 0.9, and choline 2.7 +/- 0.5 mmol/l. The NAA concentration was significantly lower in the cord than in the brainstem (Mann-Whitney, P < 0.025), and higher than in the cortex (P < 0.005) and cerebellum (P < 0.005). Cr was significantly lower in the cord than in the cerebellum (P < 0.05). There were no significant differences between Cr concentrations in the spinal cord compared to the cortex and brainstem.

Mitochondrial dysfunction in Friedreich's ataxia: from pathogenesis to treatment perspectives.

Friedreich's ataxia (FRDA), the most common inherited ataxia, is an autosomal recessive degenerative disorder caused by a GAA triplet expansion or point mutations in the FRDA gene on chromosome 9q13. The FRDA gene product, frataxin, is a widely expressed mitochondrial protein, which is severely reduced in FRDA patients. The demonstration that deficit of frataxin in FRDA is associated with mitochondrial iron accumulation, increased sensitivity to oxidative stress, deficit of respiratory chain complex activities and in vivo impairment of cardiac and skeletal muscle tissue energy metabolism, has established FRDA as a "new" nuclear encoded mitochondrial disease. Pilot studies have shown the potential effect of antioxidant therapy based on idebenone or coenzyme Q10 plus Vitamin E administration in this condition and provide a strong rationale for designing larger randomized clinical trials.

Reversible brain injury in a head-injured patient identified by magnetic resonance imaging and spectroscopy.

Serial MRI studies of a severely head-injured patient showed extensive diffusion abnormalities lasting for 40 days. These were related to initial perfusion abnormalities and improved in parallel with clinical status. Spectroscopy showed diffuse damage and pH changes. Together these data support a role for ischaemia in head injury.

Cardiac energetics are abnormal in Friedreich ataxia patients in the absence of cardiac dysfunction and hypertrophy: an in vivo 31P magnetic resonance spectroscopy study.

OBJECTIVE: Friedreich ataxia (FRDA), the commonest form of inherited ataxia, is often associated with cardiac hypertrophy and cardiac dysfunction is the most frequent cause of death. In 97%, FRDA is caused by a homoplasmic GAA triplet expansion in the FRDA gene on chromosome 9q13 that results in deficiency of frataxin, a mitochondrial protein of unknown function. There is evidence that frataxin deficiency leads to a severe defect of mitochondrial respiration associated with abnormal mitochondrial iron accumulation. To determine whether bioenergetics deficit underlies the cardiac involvement in Friedreich ataxia (FRDA) we measured cardiac phosphocreatine to ATP ratio non-invasively in FRDA patients. METHODS AND RESULTS: Eighteen FRDA patients and 18 sex- and age-matched controls were studied using phosphorus MR spectroscopy and echocardiography. Left ventricular hypertrophy was present in eight FRDA patients while fractional shortening was normal in all. Cardiac PCr/ATP in FRDA patients as a group was reduced to 60% of the normal mean (P<0.0001). In the sub-group of patients with no cardiac hypertrophy PCr/ATP was also significantly reduced (P<0.0001). CONCLUSION: Cardiac bioenergetics, measured in vivo, is abnormal in FRDA patients in the absence of any discernible deterioration in cardiac contractile performance. The altered bioenergetics found in FRDA patients without left ventricle hypertrophy implies that cardiac metabolic dysfunction in FRDA precedes hypertrophy and is likely to play a role in its development.

Daytime liver glycogen accumulation, measured by 13C magnetic resonance spectroscopy, in young children with Type 1 diabetes mellitus.

AIM: To examine daytime liver glycogen accumulation in prepubertal children with Type 1 diabetes mellitus (Type 1 DM) compared with non-diabetic controls. METHODS: Liver glycogen content was ascertained in the fasting (morning) and fed (afternoon) state using 13C magnetic resonance (MR) spectroscopy. Data were analysed from six children with Type 1 DM (median (range) age 8.7 (6.3-12.2) years), who were all on conventional insulin regimens, and six healthy controls (age 8.9 (7-10.2) years). RESULTS: Children with diabetes tended to have lower fasting glycogen values than controls but this did not reach statistical significance (median (range) 154 (70-177) vs. 178 (120-203) mM glycosyl units, Type 1 DM vs. controls respectively; P = 0.06). Glycogen increased in all children with diabetes during the day and concentrations were similar to those in controls by the afternoon (175 (157-299) vs. 172 (136-238) mM glycosyl units; P = 0.7). CONCLUSIONS: The ability of young children with Type 1 DM to replace liver glycogen depleted after an overnight fast was at least as good as that in control subjects, suggesting that impaired glycogen storage is not a contributory factor in nocturnal hypoglycaemia.

Abnormal cerebral blood volume in regions of contused and normal appearing brain following traumatic brain injury using perfusion magnetic resonance imaging.

Following traumatic brain injury, there may be secondary alterations in cerebrovascular parameters leading to ischemia and further cellular damage. To assess possible subacute hemodynamic disturbances following traumatic brain injury, we used conventional and perfusion magnetic resonance imaging (MRI) in 18 patients, on average 10 days following injury. Six of the 18 patients had focal contusions or edema visible on conventional MRI. These six patients had a significantly reduced normalized regional cerebral blood volume (rCBV) in the regions of focal pathology compared to equivalent areas in control subjects (patients 0.47 +/- 0.20 [means +/- SD], controls 1.02 +/- 0.11, p < 0.001). In addition, four of these six patients had an increased rCBV (outside control range) in the region of normal appearing brain immediately surrounding the contusion. These six patients were more significantly injured and had a worse clinical outcome compared to the remaining patients (p = 0.004,p = 0.03, respectively). There were five patients who had a region of reduced rCBV (outside control range) in a quadrant of normal appearing white matter, away from any visible abnormality, who were not more significantly injured than the remaining patients but went on to have a significantly poorer clinical outcome (p = 0.27, p = 0.01, respectively). Traumatic brain injury is a heterogeneous insult causing a variety of pathology, not all of which is visible using conventional imaging methods. The current study has shown that regions of both normal appearing and contused brain may have an abnormal rCBV and that alterations in rCBV may play a role in determining the clinical outcome of patients.

Characterization of artifact simulating aortic dissection in computed tomography imaging.

An artifact simulating aortic dissection has been seen in computed tomography (CT) and reported in numerous journals. The purpose of this study is to determine the origin. A phantom was constructed to simulate the motion of the ascending aorta during the cardiac cycle. Technique factors such as scan time, slice thickness, pitch, and reconstruction algorithms were examined for their effect on the simulated dissection appearance. Change in the angle of the simulated aorta with respect to the scanner axis was also studied. CT images displaying the simulated aortic dissection are obtained reproducibly. The amplitude of the artifact is more pronounced for increased scan time. The artifact amplitude is proportional to the displacement of the phantom. The simulated aortic dissection seems to be more pronounced when the scan time is comparable to the cycling time of aortic motion.

Antioxidant treatment improves in vivo cardiac and skeletal muscle bioenergetics in patients with Friedreich's ataxia.

Friedreich's ataxia (FA) is the most common form of autosomal recessive spinocerebellar ataxia and is often associated with a cardiomyopathy. The disease is caused by an expanded intronic GAA repeat, which results in deficiency of a mitochondrial protein called frataxin. In the yeast YFH1 knockout model of the disease there is evidence that frataxin deficiency leads to a severe defect of mitochondrial respiration, intramitochondrial iron accumulation, and associated production of oxygen free radicals. Recently, the analysis of FA cardiac and skeletal muscle samples and in vivo phosphorus magnetic resonance spectroscopy (31P-MRS) has confirmed the deficits of respiratory chain complexes in these tissues. The role of oxidative stress in FA is further supported by the accumulation of iron and decreased aconitase activities in cardiac muscle. We used 31P-MRS to evaluate the effect of 6 months of antioxidant treatment (Coenzyme Q10 400 mg/day, vitamin E 2,100 IU/day) on cardiac and calf muscle energy metabolism in 10 FA patients. After only 3 months of treatment, the cardiac phosphocreatine to ATP ratio showed a mean relative increase to 178% (p = 0.03) and the maximum rate of skeletal muscle mitochondrial ATP production increased to 139% (p = 0.01) of their respective baseline values in the FA patients. These improvements, greater in prehypertrophic hearts and in the muscle of patients with longer GAA repeats, were sustained after 6 months of therapy. The neurological and echocardiographic evaluations did not show any consistent benefits of the therapy after 6 months. This study demonstrates partial reversal of a surrogate biochemical marker in FA with antioxidant therapy and supports the evaluation of such therapy as a disease-modifying strategy in this neurodegenerative disorder.

Altered cellular metabolism following traumatic brain injury: a magnetic resonance spectroscopy study.

Experimental studies have reported early reductions in pH, phosphocreatine, and free intracellular magnesium following traumatic brain injury using phosphorus magnetic resonance spectroscopy. Paradoxically, in clinical studies there is some evidence for an increase in the pH in the subacute stage following traumatic brain injury. We therefore performed phosphorus magnetic resonance spectroscopy on seven patients in the subacute stage (mean 9 days postinjury) following traumatic brain injury to assess cellular metabolism. In areas of normal-appearing white matter, the pH was significantly alkaline (patients 7.09 +/- 0.04 [mean +/- SD], controls 7.01 +/- 0.04, p = 0.008), the phosphocreatine to inorganic phosphate ratio (PCr/Pi) was significantly increased (patients 4.03 +/- 1.18, controls 2.64 +/- 0.71, p = 0.03), the inorganic phosphate to adenosine triphosphate ratio (Pi/ATP) was significantly reduced (patients 0.37 +/- 0.10, controls 0.56 +/- 0.19, p = 0.04), and the PCr/ATP ratio was nonsignificantly increased (patients 1.53 +/- 0.29, controls 1.34 +/- 0.19, p = 0.14) in patients compared to controls. Furthermore, the calculated free intracellular magnesium was significantly increased in the patients compared to the controls (patients 0.33 +/- 0.09 mM, controls 0.22 +/- 0.09 mM, p = 0.03)). Proton spectra, acquired from similar regions showed a significant reduction in N-acetylaspartate (patients 9.64 +/- 2.49 units, controls 12.84 +/- 2.35 units, p = 0.03) and a significant increase in choline compounds (patients 7.96 +/- 1.02, controls 6.67 +/- 1.01 units, p = 0.03). No lactate was visible in any patient or control spectrum. The alterations in metabolism observed in these patients could not be explained by ongoing ischemia but might be secondary to a loss of normal cellular homeostasis or a relative alteration in the cellular population, in particular an increase in the glial cell density, in these regions.

Non-bullous ichthyosiform erythroderma associated with retinitis pigmentosa.

Non-bullous ichthyosiform erythroderma (NBIE) is an autosomal recessive condition characterized by generalized erythema and scaling. Two brothers with NBIE and retinitis pigmentosa are reported. One of them also had a marfanoid habitus, thoracic kyphosis, and arachnodactyly, and was heterozygous for alpha 1 antitrypsin deficiency. A third brother had skin involvement, but normal vision. Retinitis pigmentosa has been described in association with NBIE as part of Rud syndrome, which is no longer considered a separate entity. Major diagnostic features of Rud syndrome, such as hypogonadism, mental retardation, and epilepsy were absent in this family. The association of NBIE with retinitis pigmentosa in this family seems distinct from any previously described, currently recognized syndrome.

Magnetic resonance spectroscopy evidence of abnormal cardiac energetics in Xp21 muscular dystrophy.

OBJECTIVES: Our aim was to measure the cardiac phosphocreatine to adenosine triphosphate ratio (PCr/ATP) noninvasively in patients and carriers of Xp21 muscular dystrophy and to correlate the results with left ventricular (LV) function as measured by echocardiography. BACKGROUND: Duchenne and Becker muscular dystrophy (the Xp21 dystrophies) are associated with the absence or altered expression of dystrophin in cardiac and skeletal muscles. They are frequently complicated by cardiac hypertrophy and dilated cardiomyopathy. The main role of dystrophin is believed to be structural, but it may also be involved in signaling processes. Defects in energy metabolism have been found in skeletal muscle in patients with Xp21 muscular dystrophy. We therefore hypothesized that a defect in energy metabolism may be part of the mechanism leading to the cardiomyopathy of Xp21 muscular dystrophy. METHODS: Thirteen men with Becker muscular dystrophy, 10 female carriers and 23 control subjects were studied using phosphorus-31 magnetic resonance spectroscopy and echocardiography. RESULTS: The PCr/ATP was significantly reduced in patients (1.55+/-0.37) and carriers (1.37+/-0.25) as compared with control subjects (2.44+/-0.33; p<0.0001 for both groups). The PCr/ATP did not correlate with LV ejection fraction or mass index. CONCLUSIONS: Altered expression of dystrophin leads to a reduction in the PCr/ATP. Since this reduction did not correlate with indexes of left ventricular function, this raises the possibility of a direct link between altered dystrophin expression and the development of cardiomyopathy in such patients.

Interleukin-1beta -induced changes in blood-brain barrier permeability, apparent diffusion coefficient, and cerebral blood volume in the rat brain: a magnetic resonance study.

The cytokine interleukin-1beta (IL-1beta) is implicated in a broad spectrum of CNS pathologies, in which it is thought to exacerbate neuronal loss. Here, the effects of injecting recombinant rat IL-1beta into the striatum of 3-week-old rats were followed noninvasively from 2 to 123 hr using magnetic resonance imaging and spectroscopy. Four hours after injection of IL-1beta (1 ng in 1 microliter), cerebral blood volume was significantly increased, the blood-brain barrier (BBB) became permeable to intravenously administered contrast agent between 4.5 and 5 hr, and the apparent diffusion coefficient (ADC) of brain water fell by 6 hr (5.42 +/- 0. 35 x 10(-4) mm(2)/sec treated, 7.35 +/- 0.77 x 10(-)(4) mm(2)/sec control; p < 0.001). At 24 hr the BBB was again intact, but the ADC, although partially recovered, remained depressed at both 24 and 123 hr (p < 0.03). Depleting the animals of neutrophils before IL-1beta injection prevented the BBB permeability at all time points, but the ADC was still depressed at 6 hr (6.64 +/- 0.34 x 10(-4) mm(2)/sec treated, 7.49 +/- 0.38 x 10(-4) mm(2)/sec control; p < 0.005). No changes were seen in brain metabolites using proton spectroscopy at 6 hr after IL-1beta. Intraparenchymal injection of IL-1beta caused a neutrophil-dependent transient increase in BBB permeability. The presence of neutrophils within the brain parenchyma significantly contributed to the IL-1beta-induced changes in cerebral blood volume and the ADC of brain water. However, IL-1beta apparently had a direct effect on the resident cell populations, which persisted well after all recruited leukocytes had disappeared. Thus the action of IL-1beta alone can give rise to magnetic resonance imaging-visible changes that are normally attributed to alterations to cellular homeostasis.