The Temporal Doppler Effect refers to the subjective perception that the past is further away than the future even when both temporal distances are objectively the same from the present moment (Caruso et al., 2013). In the current study

Rosaria Talarico, Silvia Aguilera, Tobias Alexander , Zahir Amoura, Ana M. Antunes, Laurent Arnaud , Tadej Avcin, Lorenzo Beretta, Stefano Bombardieri, Gerd R. Burmester, Sara Cannizzo, Lorenzo Cavagna, Benjamin Chaigne, Alain Cornet, Nathalie CostedoatChalumeau, Andrea Doria, Alessandro Ferraris, Rebecca FischerBetz, João E. Fonseca, Charissa Frank, Andrea Gaglioti, Ilaria Galetti, Jürgen Grunert, Vera Guimarães, Eric Hachulla, Frederic Houssiau, Luca Iaccarino, Thomas Krieg, Marteen Limper, Fransiska Malfait , Xavier Mariette, Diana Marinello , Thierry Martin, Lisa Matthews, Marco MatucciCerinic, Alain Meyer, Carlomaurizio Montecucco, Luc Mouthon, Ulf MüllerLadner, Simona Rednic, Vasco C. Romão, Matthias Schneider, Vanessa Smith, Alberto Sulli, Farah Tamirou, Domenica Taruscio, Anna V. Taulaigo, Enrique Terol, Angela Tincani, Simone Ticciati, Giuseppe Turchetti, P. Martin van Hagen, Jacob M. van Laar, Ana Vieira, Jeska K. de VriesBouwstra, Maurizio Cutolo and Marta Mosca

COVID‑19 is a devastating disease, and its control is difficult due to its high transmissibility rate and a long incubation average period (6.4 days). Additionally, more than half of the infected patients were asymptomatic young people or children. The asymptomatic virus transmission is the actual challenge to controlling the disease. Because of limited treatment options, diagnosis techniques have been the first focus all over the world, involving q-RT-PCR as a gold standard, serological tests, point of care studies, or RT-LAMP. Generally, nasopharyngeal, and oropharyngeal samples are preferred clinically as sources. However, alternative sources are being researched, particularly for healthcare professionals who have difficulty taking samples, patients who are afraid of giving samples, and pediatric patients. Herein, physiological saline has been utilized to offer an alternative source besides the swab samples for use in q-RT-PCR. In this study, 212 randomly chosen patients’ samples were studied, and we evaluated the concordance and accurate q-RT-PCR results in two different sources, obtained from swab and gargle samples of patients. Herein, physiological saline is utilized, which is widely used medically as a recommended irrigating and wound dressing solution. We obtained in our experiments with this method, the confidence interval determines 74.50% positivity when compared to the routine q-RT-PCR procedure as summarized. In addition, when only the gargle sampling method is studied in low-income countries, the cost of testing for COVID-19 will decrease significantly. Because this method does not require vNAT or VTM transport solution sterile swab sticks as shown. The plastic container with a lid in which the patient can gargle with SF and spit it out is an ideal method for this. Additionally, it provides a great cost-benefit in low-income countries.

Genotype G3 rotaviruses rank among the most common rotavirus strains worldwide in humans and animals. However, despite a robust long-term rotavirus surveillance system from 1997 in Blantyre, Malawi, these strains were only detected from 1997 to 1999 and then disappeared and re-emerged in 2017, five years after the introduction of the Rotarix rotavirus vaccine. Here we analysed 27 whole genome sequences to understand how G3 strains re-emerged in Malawi. We randomly selected samples each month between November 2017 and August 2019 from stool samples of children hospitalised with acute diarrhoea at the Queen Elizabeth Hospital in Blantyre, Malawi. We found three genotypes namely G3P[4] (n=20), G3P[6] (n=1) and G3P[8] (n=6) associated with the re-emergence of G3 strains in Malawi post-Rotarix vaccine introduction. The identified genotypes co-circulated at different time points and were associated with three typical human G3 strains consisting of either a Wa-like or DS-1-like genetic constellation and reassortant strains possessing Wa-like and DS-1-like genetic backbones. Time-resolved phylogenetic trees demonstrated that the most recent common ancestor for each segment of the re-emerged G3 strains emerged between 1996 and 2012, possibly through introductions from outside the country due to the limited genetic similarity with G3 strains which circulated before their disappearance in the late 1990s. Further genomic analysis revealed that the reassortant DS-1-like G3P[4] strains acquired a Wa-like NSP2 genome segment (N1 genotype) through intergenogroup reassortment; an artiodactyl-like VP3 through intragenogroup interspecies reassortment; and VP6, NSP1 and NSP4 segments through intragenogroup reassortment likely before importation into Malawi. Additionally, the re-emerged G3 strains contain amino acid substitutions within the antigenic regions of the VP4 proteins which could potentially impact the binding of rotavirus vaccine-induced antibodies. Altogether, our findings shows that multiple rather than a single genotype have driven the re-emergence of G3 strains likely from other countries highlighting the role of human mobility and genome reassortment events in the dissemination and evolution of rotavirus strains in Malawi necessitating the need for long-term genomic surveillance of rotavirus in high disease burden settings to inform disease prevention and control.

Background and Study Aim. Various experimental programs for the development of motor skills are present in sports activities. Explosive strength can be defined as the ability to produce maximum force as soon as possible, and it represents an essential factor in activities where it is necessary to increase the acceleration of the body mass, the mass of specific body parts, or of an external object. The aim of study – to determine the effects of an experimental program on the explosive strength of lower limbs in male adolescents. Material and Methods. One hundred and one male adolescent (aged 19 years ± 6 months; body height 181.43 ± 7.42 cm; body mass 80.08 ± 10.07 kg) were recruited and randomly divided into two groups: experimental group (E; N=48) and control group (K; N=48). The E group performed the experimental program which lasted fifteen weeks and consisted of three 60-min training sessions per week. All participants were tested on Squat Jump (SJ), Countermovement Jump (CMJ), Countermovement Jump with arms (CMJa) and Continuous Jump with Straight Legs (CJSL). The four tests were performed using a Kistler force platform to measure Quatro Jump Bosco Protocol Version 1.0.9.2 and gave us data about the jump height, number of jumps for 15s, average power jump and peak power jump. The multivariate analysis covariance (MANCOVA) and follow up analysis covariance (ANCOVA) were used to analyze the data. Results. The results of MANCOVA showed statistically significant differences (p ≤ 0.001) between the E and K groups in all systems of variable lower limb explosive strength in male adolescents. In addition, results of ANCOVA showed statistically significant differences (p ≤ 0.001) in SJ, CMJ, CMJa and CJSL in favor of the E group compared to the K one. Conclusions. The results of this research show that a fifteen-week experimental program can lead to significant improvements in lower limb explosive strength in male adolescents.

Kupres cheese is a traditional Bosnian full-fat hard cheese. This paper deals with the change of protein and fatty acid profiles, mineral content and antioxidant potential during the period of three months of its ripening. Proteolysis was monitored by the electrophoresis of total extracts and water-soluble fractions under reducing conditions, whereas fatty acid profiles were determined by gas chromatography. The mineral content in the ripened cheeses was determined by using methods of Inductively coupled plasma - optical emission spectrometry (ICP-OES) for microelements and Inductively coupled plasma mass spectrometry (ICP-MS) for microelements, respectively. Ripening of Kupres cheese during three months is characterised by a relatively slow proteolysis, especially during the first month and by the increase in desirable fatty acid content. After 30 days of ripening, the WSN/TN and TCA/TN contents increased from 8.23% and 2.25% to 10.15% and 3.59%, respectively. Further, ripening induced higher increase of these parameters and more intensive degradation of the major caseins, especially αs-CN. After three months of ripening, residual level of αs-CN and β-CN was 12.02% and 80.96%, respectively. Three month-old cheese had improved indexes of lipid quality as well as improved reducing power and ability to scavenge free radicals. Ripening affected the content of Ca, P and Na whereas no significant changes of the other macro- and microelements of Kupres cheese were observed.

Preventing unplanned hospitalisations, including readmissions and re-presentations to the emergency department, is an important strategy for addressing the growing demand for hospital care. Significant successes have been reported from interventions put in place by hospitals to reduce their incidence. However, there is limited use of data-driven algorithms in hospital services to identify patients for enrolment into these intervention programs. Here we present the results of a study aiming to develop algorithms deployable at scale as part of a state government’s initiative to address rehospitalizations and which fills several gaps identified in the state-of-the-art literature. To the best of our knowledge, our study involves the largest-ever sample size for developing risk models. Logistic regression, random forests and gradient boosted techniques were explored as model candidates and validated retrospectively on five years of data from 27 hospitals in Queensland, Australia. The models used a range of predictor variables sourced from state-wide Emergency Department(ED), inpatient, hospital-dispensed medications and hospital-requested pathology databases. The investigation leads to several findings: (i) the advantage of looking at a longer patient data history, (ii) ED and inpatient datasets alone can provide useful information for predicting hospitalisation risk and the addition of medications and pathology test results leads to trivial performance improvements, (iii) predicting readmissions to the hospital was slightly easier than predicting re-presentations to ED after an inpatient stay, which was slightly easier again than predicting re-presentations to ED after an EDstay, (iv) a gradient boosted approach (XGBoost) was systematically the most powerful modelling approach across various tests.

This letter to editor contains an overview of commentary article in which the authors explain how they designed the novel biomarker. The Electrophysiologic Coefficient of Depressiveness - δEPCD detects the presence of a depressive disorder while being able to quantify its severity. This biomarker follows vital function - high frequency heart rate variability in relation with neuroactive metabolic components - concentration ratio between quinolinic acid, and kynurenine acid and it is both sensitive and specific in regard to depressive disorders. Diagnostics of depressive disorders could be improved by checking this novel biomarker and/or re-assessment of individuals who might have depression as well as in rising the awareness about the depressive disorders' prevalence and treatment. So far biomarkers have been classified as dynamic (descriptive) or static (prognostic). With this new complex biomarker, that comprises potentials of both categories, we might be able to introduce a new category - a physiological biomarker. Physiological biomarkers should not have exclusive application within the depressive disorder, but the future research should identify more physiological biomarkers related to other diseases.However, the findings need further evidence procuring new information regarding diagnostics of depressive disorders. Though it presents a novel methodology which would add to a biomarkers research, more specifically type-classification, lack of clear and concise protocol regarding clinical interpretation and a consistent administrative structure and/or logistics to perform the measurements are present. For this reason, further research in different settings and on a larger sample size are necessary.

In a recent study published in Nature Serger connected intermittent fasting (IF) to gut microbiome alterations and enhanced peripheral nerve regeneration following injury. 1 Fasting has been purported to have neuroregenerative effects, but the underlying mechanisms remained unclear. The authors found that IF-induced elevation of IPA (a microbiome-derived metabolite) promotes neutrophil in fi ltration into the dorsal root ganglia (DRG), which enhances the regeneration of sciatic nerve fi bers 1). 2 for

The Hedgehog (Hh) signaling pathway is essential for normal embryonic development, while its hyperactivation in the adult organism is associated with the development of various cancers. The role of the Hh signaling pathway in ovarian cancer has not been sufficiently investigated. Therefore, the present study investigated the role of protein patched homolog 1 (PTCH1), a component of the Hh signaling pathway, and changes in the promoter methylation status of the corresponding gene in a cohort of low-(LGSC) and high-grade serous ovarian carcinomas (HGSC) and HGSC cell lines (OVCAR8 and OVSAHO). PTCH1 protein expression level was analyzed using immunohistochemistry in tissue samples and immunofluorescence and western blotting in cell lines. DNA methylation patterns of the PTCH1 gene were analyzed using methylation-specific PCR. PTCH1 protein expression was significantly higher in HGSCs and LGSCs compared with controls (healthy ovaries and fallopian tubes). Similarly, ovarian cancer cell lines exhibited significantly higher PTCH1 protein expression compared with a normal fallopian tube non-ciliated epithelial cell line (FNE1). PTCH1 protein fragments of different molecular weights were detected in all cell lines, indicating possible proteolytic cleavage of this protein, resulting in the generation of soluble N-terminal fragments that are translocated to the nucleus. DNA methylation of the PTCH1 gene promoter was exclusively detected in a proportion of HGSC (13.5%) but did not correlate with protein expression. PTCH1 protein was highly expressed in serous ovarian carcinoma tissues and cell lines, while PTCH1 promoter methylation was only detected in HGSC. Further investigation is required to elucidate the possible mechanisms of PTCH1 activation in serous ovarian carcinomas.

Introduction: The process of protein synthesis is a vital process for all kingdoms of life. The ribosome is a ribonucleoprotein complex that reads the genetic code, from messenger RNA (mRNA) to produce proteins and to tightly regulate and ensure cells growth. The fact that numerous diseases are caused by defect during the ribosome biogenesis is important to understand this pathway. Materials and methods: We have analyzed the literature for ribosome biogenesis and its links with different diseases which have been found. Results and discussion: We have discussed the key aspect of human ribosome biogenesis and its links to diseases. We have also proposed the potential of applying this knowledge to the development of a ribosomal stress-based cancer therapy. Conclusion: Major challenges in the future will be to determine factors which play a pivotal role during ribosome biogenesis. Therefore, more anti-cancer drugs and gene therapy for genetic diseases will be developed against ribosomal biogenesis in the coming years. Graphical abstract: