ARTICLE | doi:10.20944/preprints201609.0093.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: metastatic breast cancer; taxanes; eribulin; observational study
Online: 26 September 2016 (11:39:32 CEST)
Taxanes have been shown to be the most effective treatment for recurrent or metastatic breast cancer. However, for patients pretreated with taxanes, more active and possibly less toxic drugs are needed. In this retrospective study, we investigated on the effectiveness and safety of eribulin mesylate in 91 taxane-refractory subjects, extracted from the ESEMPIO database, which included 497 metastatic breast cancer patients treated with eribulin allover the Italy. This analysis included only those patients who have shown disease progression while receiving taxane therapy (primary refractory), or those who achieved a response followed by progression while still on therapy (taxane failure). Overall, 41/91 patients (45.2%) showed a clinical benefit; 1 complete response (2.2%) and 16 partial responses (17.6%) were observed. The median progression free survival was 3.1 months (95% CI: 2.8–3.5) and the median overall survival was 11.6 months (95% CI: 8.7–16.7). With regard to toxicity, 53 patients (58%) experienced asthenia/fatigue, 23 (25%) showed peripheral neurotoxicity, 18 (20%) alopecia, 12 (13%) mild constipation and 27 (30%) neutropenia. The toxicity related to the treatment led to eribulin dose reduction in 19 (21%) and discontinuation in 9 (10%) patients, respectively. In conclusion, this study suggests that eribulin is effective and well tolerated also in taxane-refractory patient.
ARTICLE | doi:10.20944/preprints202110.0160.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: allergic severe asthma; anti-IgE; Omalizumab; observational study; children
Online: 11 October 2021 (13:54:56 CEST)
Background: Asthma is the most common chronic disease affecting children and altering their quality of life. The severity of asthma is often modulated by immunoglobulin E (IgE)-mediated allergen sensitization and is associated with comorbid allergic dis-eases. Omalizumab is a humanized monoclonal antibody anti-IgE, the first biological therapy approved to treat patients aged ≥6 years with severe allergic asthma. The primary objective of our study was to investigate the efficacy and safety of Omali-zumab in Romanian paediatric patients with severe allergic asthma. Methods: In this observational real-life study, 12 children aged 6 to 18 years, (mean age 12.4 years ) with severe allergic asthma received Omalizumab as an add-on treatment. The levels of asthma control, exacerbations, lung function and adverse events were evaluated at baseline and after the first year of treatment. Results: We noticed general improvements in total asthma symptom scores and the rate of exacerbation of severe asthma. Omalizumab increased the initial variables of lung function, and no serious adverse reactions were reported. FEV1 improved statistically significant after one year of treatment with Omalizumab, [ΔFEV1 (% pred.) =18.3, and similarly, ΔMEF50 (%) = 25.8]. The mean severe exacerbation rates due to asthma decreased from 4.1 (2.8 SD) to 1.15 (0.78 SD) during the treatment year (p<0.0001) with Omalizumab. Conclusions: Treatment with Omalizumab can be an effective and safe therapeutic option for Romanian children with severe allergic asthma, providing clinically relevant in-formation on asthma control and exacerbation rate in children and adolescents. The results highlighted the effect of Omalizumab in young patients, starting from the first year of treatment.
REVIEW | doi:10.20944/preprints202004.0279.v1
Online: 16 April 2020 (13:47:49 CEST)
Objectives: This study aims to identify, report, and analyze registered and published clinical trials and observational studies for the pharmacological treatment of COVID-19 conducted in China. Methods: A strategic search was conducted via the Chinese Clinical Trial Registry to identify and extract clinical trials and observational studies registered and conducted in China for the pharmacological treatment of COVID-2019 between January 1st, 2020 and March 21st, 2020. This was further supplemented by searches conducted via the China National Knowledge Infrastructure (CNKI) database, the MEDLINE database, the World Health Organization (WHO) database, and MedRxiv and BioRxiv electronic platforms for preprint articles, published up until April 8th, 2020. Studies available in Chinese and English were included in the searches and extracted. A primary descriptive analysis was performed for registered clinical trials and observational studies identified in the Chinese Clinical Trial Registry based on the extraction of the following clinical study information: trial ID, planned date of enrollment, recruitment status, study design, population, sample size, intervention/exposure group, control /reference group, dosage, and primary outcomes. A secondary descriptive analysis was performed for published clinical trials and observational studies identified from the supplementary databases based on the extraction of the following published clinical study information: study design, population, intervention/exposure group, control /reference group and main results as appropriate. Results: A total of 221 clinical trials and observational studies were included from all databases searched. From the Chinese Clinical Trial Registry, 195 registered clinical studies including 170 clinical trials and 25 observational studies were identified and included for primary analysis. From the supplementary databases, 26 published clinical studies including 8 clinical trials and 18 observational studies were included for secondary analysis. Of these 26 published clinical studies, 18 studies, including 3 clinical trials and 15 observational studies were identified from CNKI, 2 studies including 1 clinical trial and 1 observational study from MEDLINE, 2 including 1 clinical trials and 1 observational studies from the WHO database, and 4 including 3 clinical trials and 1 observational studies from MedRxiv and BioRxiv platforms. In the primary analysis, among the 170 clinical trials included from the Chinese Clinical Trial Registry, 101 investigated western medicines (WMs), while 15 investigated Traditional Chinese Medicines (TCMs), and 54 investigated a combination of TCMs and WMs. Among the 25 included observational studies from the Chinese Clinical Trial Registry, 2 investigated WMs, 2 investigated TCMs, and 21 investigated a combination of TCMs and WMs. The total number of exposed patients in all 195 clinical studies from the Chinese Clinical Trial Registry amounted to 24,500. In the secondary analysis, treatment with Lopinavir-ritonavir and treatment with Hydroxychloroquine was not associated with a difference from standard of care in the rate of RT-PCR negativity; treatment with a combination of Lopinavir-ritonavir, interferon α, and Lian-Hua-Qing-Wen capsule was found to significantly improve the effective rate of treatment compared with Interferon α combined with Lian-Hua-Qing-Wen capsule. Conclusions: China is generating a massive source of evidence that is critical for defeating the COVID-19 pandemic. Not only the clinical experience, but also the scientific evidence should be shared with the global scientific community.
REVIEW | doi:10.20944/preprints201810.0636.v1
Subject: Medicine & Pharmacology, Other Keywords: abdominal aortic aneurysm, risk factors, observational studies, meta-analysis
Online: 26 October 2018 (15:28:44 CEST)
Abdominal aortic aneurysm (AAA) represents an important public health problem with a prevalence between 1.3% and 12.5%. Several population-based randomized trials have evaluated ultrasound screening for AAA providing evidence of a reduction in aneurysm-related mortality in the screened population. The aim of our study was to perform a systematic review and meta-analysis of the risk factors for AAA. We conducted a systematic review of observational studies and we performed a meta-analysis that evaluated the following risk factors: gender, smoking habits, hypertension, diabetes mellitus, Coronary Artery Disease and family history of AAA. Abdominal aortic aneurysm prevalence is higher in smokers and in males. It is important to underline that all countries, where AAA screening was set up, had high income level and the majority belong to Western Europe (United Kingdom, Sweden, Italy, Poland, Spain and Belgium). Abdominal aortic aneurysm screening is fundamental for public health. It would avoid deaths, ruptures, and emergency surgical interventions if abdominal aortic aneurysm was diagnosed early in the population target for screening.
ARTICLE | doi:10.20944/preprints202112.0039.v1
Subject: Physical Sciences, Astronomy & Astrophysics Keywords: relativistic astrophysics; theoretical and observational cosmology; redshift; Hubble parameter; quasar
Online: 2 December 2021 (12:54:08 CET)
Here we use the flat Friedmann-Lemaitre-Robertson-Walker metric describing a spatially homogeneous and isotropic universe to derive the cosmological redshift distance in a way which differs from that which can be found in the astrophysical literature. We use the co-moving coordinate re (the subscript e indicates emission) for the place of a galaxy which is emitting photons and ra (the subscript a indicates absorption) for the place of an observer within a different galaxy on which the photons - which were traveling thru the universe - are absorbed. Therefore the real physical distance - the way of light - is calculated by D = a(t0) ra - a(te) re. Here means a(t0) the today’s (t0) scale parameter and a(te) the scale parameter at the time of emission (te) of the photons. Nobody can doubt this real travel way of light: The photons are emitted on the co-moving coordinate place re and are than traveling to the co-moving coordinate place ra. During this traveling the time is moving from te to t0 (te ≤ t0) and therefore the scale parameter is changing in the meantime from a(te) to a(t0). Using this right way of light we calculate some relevant classical cosmological equations (effects) and compare these theoretical results with some measurements of astrophysics. As one result we get e.g. the today’s Hubble parameter H0a ≈ 62.34 km/(s Mpc). This value is smaller than the Hubble parameter H0,Planck ≈ 67.66 km/(s Mpc) resulting from Planck 2018 data  which is discussed in the literature.
ARTICLE | doi:10.20944/preprints201907.0072.v1
Subject: Social Sciences, Other Keywords: performance analysis; football; gender differences; LaLiga; technical-tactical behaviour; observational methodology
Online: 4 July 2019 (09:38:22 CEST)
The aim of this study was to identify gender differences in technical-tactical behaviour in football. To this end 68 matches of the first division of the Spanish men’s and women´s league, corresponding to 2016/17 season were analyzed. A comparison of medians was carried out using the Mann-Whitney U-test were conducted as post hoc test and a grouping of the variables through the clustering bootstrapping technique in both groups. We have detected statistically significant differences regarding all accurate passes, in favour of men, as well as a greater number of yellow cards. In female football, a greater number of picking up free balls, interceptions, lost balls, recoveries, challenges and attacks, both positional and counterattacks, are produced. The clustering analysis also allowed that in male football, the circumstance of receiving a red card is closely related to the number of goals conceded and most of the shots on goal are achieved by positional attacks. In women's football, ball possession on own half is closely related to the number of losses. These results could be useful for gender-specific training information for optimal preparation. However, more research is warranted to establish the main gender differences and characterize women's football.
ARTICLE | doi:10.20944/preprints202208.0225.v1
Subject: Life Sciences, Other Keywords: hemoglobin; iron nutrition status; metabolic syndrome; metabolic disorders; observational study; Taiwanese Han Chinese; European White
Online: 12 August 2022 (04:03:24 CEST)
Iron overnutrition has been implicated with higher risk of developing metabolic and cardiovascular diseases, including metabolic syndrome (MetS), while iron deficiency anemia exacerbates many underlying chronic conditions. Hemoglobin (Hb) concentration in the blood, which reflects a major functional iron (i.e., heme iron) in the body, may serve as a surrogate of iron nutrition status. We conducted sex-specific observational association studies where we carefully titrated the association between Hb deciles and MetS and its components among the Taiwanese Han Chinese (HC) from the Taiwan Biobank and Europeans of White ancestry from the UK Biobank, representing two large ethnicities. Our data show that at higher-than-normal levels of Hb, increasing deciles of Hb concentration were significantly associated with MetS across all sex subgroups in both ethnicities, with the highest deciles resulting in up to three times greater risks than the reference group [Taiwanese HC: OR=3.17 (95% CI, 2.75-3.67) for Hb >16.5 g/dL in men, OR=3.11 (2.78-3.47) for Hb >14.5 g/dL in women; European Whites: OR=1.89 (1.80-1.98) for Hb >16.24 g/dL in men, OR=2.35 (2.24-2.47) for Hb >14.68 g/dL in women]. The association between stronger risks and increasing Hb deciles was similarly observed with all metabolic components except diabetes. Here we found that both the highest Hb decile groups and contrarily the lowest ones, with respect to the reference, were associated with higher odds of diabetes in both ethnic groups [e.g., Taiwanese HC men: OR=1.64 (1.33-2.02) for Hb >16.5 g/dL, OR=1.71 (1.39-2.10) for Hb <13.5 g/dL; European Whites women: OR=1.39 (1.26-1.45) for Hb >14.68 g/dL, OR=1.81 (1.63-2.01) for Hb <12.39 g/dL]. These findings confirm that elevated Hb concentrations, a potential indicator of iron overnutrition, may play a role in the pathophysiology of MetS and metabolic components.
ARTICLE | doi:10.20944/preprints202201.0238.v1
Subject: Physical Sciences, Astronomy & Astrophysics Keywords: relativistic astrophysics; theoretical and observational cosmology; redshift; Hubble parameter; quasar; black hole; SNIa; galaxy; M87
Online: 17 January 2022 (15:28:25 CET)
In this part of the two-part series of essays, we first derive some equations for further physical redshift distances. We then analyze a catalog with 132,975 quasars, for which both the apparent magnitude m and the redshift z are given, in order to find the today’s value of the parameter β0 of the theory presented. We then use this value to determine the today’s value of the radius R0a of the Friedmann sphere using a magnitude redshift diagram of 19 SNIa. With the help of the known values of R0a and β0, statements about astrophysical data from the black hole in the galaxy M87 can be made. In addition, the today’s Hubble parameter H0 results from both parameters. Furthermore, we calculate the values of the further physical redshift distances for the black hole in M87 and all 19 SNIa. The resulting parameter values are: β0 ≈ 0.731, R0a ≈ 2,712.48 Mpc and H0 ≈ 65.638 km / (s ∙ Mpc). The today’s mass density of the Friedmann sphere is ρ0 ≈ 4.843 x 10-27 g / cm 3. For the mass of the Friedmann sphere we find MFK ≈ 1.206 x 1056 g. Annotation: Knowledge of the first part  of the series of articles is a prerequisite for understanding this article.
REVIEW | doi:10.20944/preprints202012.0423.v1
Subject: Medicine & Pharmacology, Allergology Keywords: breakfast skipping; overweight; obesity; weight gain; BMI change; systematic review; meta-analysis; observational longitudinal studies
Online: 17 December 2020 (11:05:41 CET)
Globally, increasing rates of obesity are one of the most important health issues. The association between breakfast skipping and body weight is contradictory between cross-sectional and interventional studies. The systematic review and meta-analyses aim to summarize this association based on observational longitudinal studies. We included prospective studies on breakfast skipping and overweight/obesity or weight change in adults. Literature was searched until September 2020 in PubMed and Web of Science. Summary RRs with a 95% CI were estimated in pairwise meta-analyses by applying a random-effects model. In total, 9 studies were included in the systematic review and 6 of them were included in the meta-analyses. The meta-analysis indicated an 13% increased RR for overweight/obesity when breakfast was skipped on ≥ 3 days per week compared to ≤ 2 days per week (95% CI: 1.06, 1.21, n=3 studies). The meta-analysis on weight change displays a 21% increased RR for weight gain for breakfast skippers compared to breakfast eaters (95% CI: 1.05, 1.40, n=2 studies). The meta-analysis on BMI change displayed no difference between breakfast skipping and eating (RR=1.02, 95% CI: 0.99, 1.05, n=2 studies). This study provides low meta-evidence for an increased risk for overweight/obesity and weight gain for breakfast skipping.
Subject: Physical Sciences, Astronomy & Astrophysics Keywords: general relativity: exact solutions; relativity and gravitation; observational cosmology; mathematical and relativistic aspects of cosmology
Online: 16 February 2020 (05:15:59 CET)
The Universe has a gravitational horizon with a radius Rh = c/H coincident with that of the Hubble sphere. This surface separates null geodesics approaching us from those receding, and as free-falling observers within the Friedmann-Lemaitre-Robertson-Walker spacetime, we see it retreating at proper speed c, giving rise to the eponymously named cosmological model Rh = ct. As of today, this cosmology has passed over 20 observational tests, often better than LCDM. The gravitational radius Rh therefore appears to be highly relevant to cosmological theory, and in this paper we begin to explore its impact on fundamental physics. We calculate the binding energy of a mass m within the horizon and demonstrate that it is equal to mc2. This energy is stored when the particle is at rest near the observer, transitioning to a purely kinetic form equal to the particle's escape energy when it approaches Rh. In other words, a particle's gravitational coupling to that portion of the Universe with which it is causally connected appears to be the origin of rest-mass energy.
REVIEW | doi:10.20944/preprints202105.0487.v1
Subject: Physical Sciences, Acoustics Keywords: black hole; supermassive black hole; black hole physics; M87 galaxies; gravitation; Event Horizon; telescope; observational astronomy
Online: 20 May 2021 (11:45:25 CEST)
M87 is a giant elliptical galaxy in the Virgo cluster of galaxies. The radio source has a core which coincides with the nucleus of the galaxy and a jet of emission which is detected from radio to X-ray bands. A supermassive black hole is assumed to be at the centre of M87 which sends out relativistic particles in the form jets along its axis of rotation. Relativistic particles accelerated in a magnetic field, give out synchrotron radiation. The centre is surrounded by an accretion disc, which is the closest that we can probe into a black hole. High resolution observations are needed to examine the nature of the radio emission closest to the centre of M87. An array of millimetre-band telescopes across the globe were used as an interferometer, called the Event Horizon Telescope, (EHT) to probe the nuclear region. The angular resolution of this interferometer array is 25 microarc sec, at a wavelength of 1.3mm and the data was carefully calibrated and imaged. The resulting image shows an asymmetric ring which is consistent with the predictions of strong gravitational lensing of synchrotron emission from hot plasma near the event horizon. In this paper, we review the results of the observations of the radio galaxy, M87, using the Event Horizon Telescope
ARTICLE | doi:10.20944/preprints201809.0187.v1
Subject: Physical Sciences, Astronomy & Astrophysics Keywords: general relativity; past lightcone gauge; direct observational approach; cosmological observables; galaxy surveys; galaxy number count; density contrast; overdensity; cosmological perturbations
Online: 11 September 2018 (08:08:39 CEST)
The lightcone gauge is a set of what are called the observational coordinates adapted to our past lightcone. We develop this gauge by producing a perturbed spacetime metric that describes the geometry of our past lightcone where observations are usually obtained. We connect the produced observational metric to the perturbed Friedmann-Lema\^itre-Robertson-Walker metric in the standard general gauge or what is the so-called 1+3 gauge. We derive the relations between these perturbations of spacetime in the observational coordinates and those perturbations in the standard metric approach, as well as the dynamical equations for the perturbations in observational coordinates. We also calculate the observables in the lightcone gauge and re-derive them in terms of Bardeen potentials to first order. A verification is made of the observables in the perturbed lightcone gauge with those in the standard gauge. The advantage of the method developed is that the observable relations are simpler than in the standard formalism, and they are expressed in terms of the metric components which in principle are measurable. We use the perturbed lightcone gauge in galaxy surveys and the calculations of galaxy number density contrast. The significance of the new gauge is that by considering the null-like light propagations the calculations are much simpler due to the non-consideration of the angular deviations.
REVIEW | doi:10.20944/preprints201702.0002.v1
Subject: Physical Sciences, Astronomy & Astrophysics Keywords: Cosmology; Observational cosmology; Origin, formation, and abundances of the elements; dark matter; dark energy; superclusters; large-scale structure of the Universe
Online: 1 February 2017 (16:06:52 CET)
The main foundations of the standard $\Lambda $CDM model of cosmology are that: 1) The redshifts of the galaxies are due to the expansion of the Universe plus peculiar motions; 2) The cosmic microwave background radiation and its anisotropies derive from the high energy primordial Universe when matter and radiation became decoupled; 3) The abundance pattern of the light elements is explained in terms of primordial nucleosynthesis; and 4) The formation and evolution of galaxies can be explained only in terms of gravitation within a inflation+dark matter+dark energy scenario. Numerous tests have been carried out on these ideas and, although the standard model works pretty well in fitting many observations, there are also many data that present apparent caveats to be understood with it. In this paper, I offer a review of these tests and problems, as well as some examples of alternative models.
REVIEW | doi:10.20944/preprints202003.0235.v2
Subject: Medicine & Pharmacology, Nutrition Keywords: acute respiratory distress syndrome (ARDS); ascorbic acid; cathelicidin; coronavirus; COVID-19; cytokine storm; influenza; observational; pneumonia, prevention; respiratory tract infection; solar radiation; treatment; UVB; vitamin C; vitamin D
Online: 30 March 2020 (05:48:43 CEST)
The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.
REVIEW | doi:10.20944/preprints201609.0096.v2
Subject: Physical Sciences, Astronomy & Astrophysics Keywords: big bang; planck scale Hubble parameter; quantum cosmology; Mach’s principle; holographic principle; observational cosmology; super luminal expansion speed; super luminal rotation speed; dark energy; cosmic rotational kinetic energy; cosmic microwave back
Online: 8 October 2016 (10:26:06 CEST)
With reference to Planck scale Hubble parameter, super luminal expansion speeds, super luminal rotation speeds, Mach’s principle and Holographic principle, we review the current cosmological observations with eight simple assumptions. By understanding Yuri N. Obukhov and V.A. Korotky proposed cosmic rotational effects of polarization of radiation due to massive bodies, to some extent cosmic rotation can be deep-rooted in an observational approach and the ratio of current angular velocity and Hubble parameter can be estimated. It is possible to show that, at H0 =70 km/sec/Mpc, current cosmic temperature, age, radius, mass, mass density are 2.721 K, 4.41x1017 sec, 90 billion light years, 1.14654x1054 kg, 0.0482 times the current critical density respectively. Clearly speaking, current universe seems to constitute 267 Hubble spheres. Important point to be noted is that, current rotational kinetic energy is 0.6667 times the current critical energy. Based on the estimated current mass density and current rotational kinetic energy, current cosmic dark matter density can be shown to be 0.2851 times the current critical density. These numerical coincidences cast serious doubt on the on the real existence of currently believed ‘dark energy’. Initial and current expansion speeds are 3x108 m/sec and 3.56x109 m/sec respectively. With increasing cosmic age and increasing cosmic expansion speed, current universe is expanding with a speed of 11.885c. By knowing the time to time future cosmic temperatures, future Hubble parameters and corresponding future cosmic expansion speeds can be estimated and thus future expansion speed can be understood. Starting from ‘speed of light’, our model assumes a continuous increase in expansion speed and attains a current radius of 90 billion light years (without inflationary concepts) and casts a serious doubt on the actuality of currently believed ‘inflation’.