Abstract Objectives The observational REAL WECAN study showed that canagliflozin 100 mg (CANA100) as add-on therapy, and canagliflozin 300 mg (CANA300), switching from prior SGLT-2i therapy, significantly improved several cardiometabolic parameters in patients with T2DM. The aim of this sub-analysis was to assess the effectiveness and safety of canagliflozin in patients aged >65 years. The primary outcome of the study was the mean change in HbA1c over the follow-up time. Materials and Methods 583 patients met the inclusion criteria (39.5% > 65 years), 279 in the CANA100 cohort (36.9 % > 65 years, mean HbA1c 8.05%) and 304 in the CANA300 cohort (41.8 % > 65 years, mean HbA1c 7.51%). Results In the CANA100 cohort, older patients showed significant reductions in HbA1c (-0.78%) and weight (-4.5 kg). Patients aged >65 years switching to CANA300 experienced a significant decrease in HbA1c (-0.27%) and weight (-2.1 kg). There were no significant differences in HbA1c and weight reductions when the cohorts of patients <65 and >65 years were compared in a multiple linear regression model. The safety profile of canagliflozin was similar in both age groups. Conclusion These findings support canagliflozin as an effective therapeutic option for older adults with T2DM

Objective. The aim of our data is to reveal the method of prognosis abnormal perinatal outcome, using combination US and Doppler results in uncomplicated pregnancies at 40 weeks and beyond. Design.1020 uncomplicated pregnant women at 40 weeks and beyond were examined 48 hours before delivery. We analyzed fetus’s condition during labor and just after. Setting. According these dates all women were divided into 3 groups after amniotic index(AI)and pulsatility indices(PI) in the middle cerebral artery(MCA). Population.260 women were included in the study because they met the inclusion criteria. Methods.All women were divided into 3 groups (group 1 - PI>0.835, any value of AI, group 2-AI >85, PI ≤ 0.835, group 3- AI ≤ 85 and PI ≤ 0.835).We analyzed fetus’s condition during labor and just after delivery (Apgar score <=7 and >7 on the 1st minute). Result. We’ve got trigger level for pulsatility index (PI) as 0.835, if we had PI less than that threshold cases of emergency cesarean section increases in 2,12 times, if PI less than 0,835 in combination with Amniotic Index(AI) 85 and less in 5,28 times. If PI =<0,835 risk of newborns having Apgar 7 and less increases in 1,18, but in combination with AI =<85 in 4,72 times. Conclusion. In results we found out the following data: low PI in the MCA may be parameter which cans prognoses fetus distress. Combination of PI reduce with low AI increases its specific and can use in practical ways to avoid hypoxic brain damage during labor.

An Association of the Arginase 1 Gene with Preschool Wheezing PhenotypesHartmut Grasemann and Fernando HolguinArginases are enzymes that metabolize L-arginine to form urea and L-ornithine. The two arginase isoforms, arginase I and arginase II, which are encoded by two different genes (ARG1 and ARG 2), are expressed in various cell types throughout the human body, including the lungs and airways. Arginase competes with nitric oxide synthase (NOS) for L-arginine as substrate, and increased arginase expression and activity in asthma reduces nitric oxide (NO) bioavailability, causing airways obstruction and contributing to reactive oxygen species production (1). Arginase also plays a role in allergen-induced airway remodeling in chronic asthma, presumably due to increased formation of L-ornithine, the precursor of L-proline and the polyamines (2). Proline is further metabolized to collagen and the polyamines putrescine, spermidine and spermine, which among other functions, also inhibit NOS. Increased production of endogenous NOS inhibitors including the polyamines as well as asymmetric dimethylarginine (ADMA), further contribute to the imbalance of NOS and arginases in asthma (figure 1).Previous studies of genetic variations or single nucleotide polymorphisms (SNPs) in arginase genes had shown associations with atopy and asthma. For example, SNPs in both arginase genes were associated with atopy and asthma in children and with risk for asthma in adults (3,4,5). Interestingly, ARG1 and ARG2 were also found to be associated with bronchodilator response in children and adults with asthma, and ARG1 with long term outcome on inhaled corticosteroid (ICS) therapy in adult asthma (5,6,7,8,9).Preschool wheeze is a common phenomenon, usually benign and mostly self-limited (10,11). Different phenotypes of preschool wheeze have been described, including early transient wheeze, late onset wheeze and persistent wheeze (12). A more recent classifications distinguishes multiple trigger wheeze (MTW) from episodic wheeze (EW), which is mainly caused by viral respiratory tract infections. The clinical usefulness of phenotype driven classifications has been questioned for a number of reasons including the longitudinal instability of phenotypes. However, some evidence suggests that MTW may be linked to later onset allergic asthma and MTW may therefore be more likely to respond to asthma treatment as compared to EW (13,14,15,16,17,18). Interestingly, a more recent analysis of the natural history of MTW and EW in two large independent birth cohorts demonstrated that phenotypes may track over time (19), suggesting that the two indeed represent different disease entities and not just differences in severity of the same disease.In a study by Gokmirza Ozdemir et al., published in this issue of theJournal , the authors report an association between arginase 1 gene polymorphisms and preschool wheezing phenotypes (20). In a cohort of 83 well characterized preschool wheezers with either multi trigger wheeze (MTW) or episodic wheeze (EW) phenotype of Turkish origin and matched controls, there was a difference in homozygous frequency of the ARG1 rs2781667T>C SNP between wheezing phenotypes and between patients with vs without allergic rhinitis. The homozygous frequency of this SNP in ARG1 was significantly higher in MTW vs EW, and in allergic rhinitis vs no allergic rhinitis. There were no associations of other tested SNPs in either ARG1 or ARG2 with preschool wheezing, allergic rhinitis, presence of aeroallergen sensitivity or tobacco exposure. Further analyses also showed significant differences in a number of haplotype frequencies in ARG1 between all wheezers and controls, and also between wheezing phenotypes. No associations were found with ARG2 in this study (20). Thus, these results show that in the population studied, variants in ARG1 but not ARG2 were associated with wheezing phenotypes in pre-school age.This observation is exiting as the genotype-phenotype association implies that arginase I could be involved in the development of preschool wheeze and wheezing phenotypes, possibly through an effect on L-arginine availability for nitric oxide synthase (NOS) or by affecting airway remodelling. However, the population studied here was relatively small and the findings have not yet been confirmed by others. Therefore, the results need to be interpreted with caution and additional studies are needed for confirmation. Similarly, it is unclear at this point, whether the SNPs and haplotypes found to be different in frequency between groups, alter arginase expression or activity, and what the biological or molecular explanation could be for the observed associations. Nevertheless, these observations by Gokmirza Ozdemir et al. are promising, and once confirmed in larger and independent cohorts, also have the potential to help develop a genetic test for wheezing pre-schoolers that may predict future asthma risk and response to asthma therapies.References1) North ML, Grasemann H, Khanna N, Inman MD, Gauvreau GM, Scott JA. Increased ornithine-derived polyamines cause airway hyperresponsiveness in a mouse model of asthma. Am J Respir Cell Mol Biol. 2013 Jun;48(6):694-702.2) Maarsingh H, Dekkers BG, Zuidhof AB, Bos IS, Menzen MH, Klein T, Flik G, Zaagsma J, Meurs H. Increased arginase activity contributes to airway remodelling in chronic allergic asthma. Eur Respir J. 2011 Aug;38(2):318-28.3) Donthi S, Neela VSK, Gaddam S, Mohammed HH, Ansari SS, Valluri VL, Sivasai KSR. Association of increased risk of asthma with elevated arginase & interleukin-13 levels in serum & rs2781666 G/T genotype of arginase I. Indian J Med Res. 2018 Aug;148(2):159-168.4) Li H, Romieu I, Sienra-Monge JJ, Ramirez-Aguilar M, Estela Del Rio-Navarro B, Kistner EO, Gjessing HK, Lara-Sanchez Idel C, Chiu GY, London SJ. Genetic polymorphisms in arginase I and II and childhood asthma and atopy. J Allergy Clin Immunol. 2006 Jan;117(1):119-26.5) Vonk JM, Postma DS, Maarsingh H, Bruinenberg M, Koppelman GH, Meurs H. Arginase 1 and arginase 2 variations associate with asthma, asthma severity and beta2 agonist and steroid response. Pharmacogenet Genomics. 2010 Mar;20(3):179-86.6) Duan QL, Gaume BR, Hawkins GA, Himes BE, Bleecker ER, Klanderman B, Irvin CG, Peters SP, Meyers DA, Hanrahan JP, Lima JJ, Litonjua AA, Tantisira KG, Liggett SB. Regulatory haplotypes in ARG1 are associated with altered bronchodilator response. Am J Respir Crit Care Med. 2011 Feb 15;183(4):449-54.7) Litonjua AA, Lasky-Su J, Schneiter K, Tantisira KG, Lazarus R, Klanderman B, Lima JJ, Irvin CG, Peters SP, Hanrahan JP, Liggett SB, Hawkins GA, Meyers DA, Bleecker ER, Lange C, Weiss ST. ARG1 is a novel bronchodilator response gene: screening and replication in four asthma cohorts. Am J Respir Crit Care Med. 2008 Oct 1;178(7):688-94.8) Sy HY, Ko FW, Chu HY, Chan IH, Wong GW, Hui DS, Leung TF. Asthma and bronchodilator responsiveness are associated with polymorphic markers of ARG1, CRHR2 and chromosome 17q21. Pharmacogenet Genomics. 2012 Jul;22(7):517-24.9) Scaparrotta A, Franzago M, Marcovecchio ML, Di Pillo S, Chiarelli F, Mohn A, Stuppia L. Role of THRB, ARG1, and ADRB2 genetic variants on bronchodilators response in asthmatic children. J Aerosol Med Pulm Drug Deliv. 2019 Jun;32(3):164-173.10) Kurukulaaratchy RJ, Matthews S, Holgate ST, Arshad SH. Predicting persistent disease among children who wheeze during early life. Eur Respir J. 2003 Nov;22(5):767-71.11) Caudri D, Wijga A, A Schipper CM, Hoekstra M, Postma DS, Koppelman GH, Brunekreef B, Smit HA, de Jongste JC. Predicting the long-term prognosis of children with symptoms suggestive of asthma at preschool age. J Allergy Clin Immunol. 2009 Nov;124(5):903-10.e1-7.12) Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med. 1995 Jan 19;332(3):133-8.13) Schultz A, Devadason SG, Savenije OE, Sly PD, Le Souëf PN, Brand PL. The transient value of classifying preschool wheeze into episodic viral wheeze and multiple trigger wheeze. Acta Paediatr. 2010 Jan;99(1):56-60.14) Sonnappa S, Bastardo CM, Wade A, Saglani S, McKenzie SA, Bush A, Aurora P. Symptom-pattern phenotype and pulmonary function in preschool wheezers. J Allergy Clin Immunol. 2010 Sep;126(3):519-26.e1-7.15) Brand PL, Baraldi E, Bisgaard H, Boner AL, Castro-Rodriguez JA, Custovic A, de Blic J, de Jongste JC, Eber E, Everard ML, Frey U, Gappa M, Garcia-Marcos L, Grigg J, Lenney W, Le Souëf P, McKenzie S, Merkus PJ, Midulla F, Paton JY, Piacentini G, Pohunek P, Rossi GA, Seddon P, Silverman M, Sly PD, Stick S, Valiulis A, van Aalderen WM, Wildhaber JH, Wennergren G, Wilson N, Zivkovic Z, Bush A. Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach. Eur Respir J. 2008 Oct;32(4):1096-110.16) Brand PL, Caudri D, Eber E, Gaillard EA, Garcia-Marcos L, Hedlin G, Henderson J, Kuehni CE, Merkus PJ, Pedersen S, Valiulis A, Wennergren G, Bush A. Classification and pharmacological treatment of preschool wheezing: changes since 2008. Eur Respir J. 2014 Apr;43(4):1172-7.17) Garcia-Marcos L, Martinez FD. Multitrigger versus episodic wheeze in toddlers: new phenotypes or severity markers? J Allergy Clin Immunol. 2010 Sep;126(3):489-90.18) van Wonderen KE, Geskus RB, van Aalderen WM, Mohrs J, Bindels PJ, van der Mark LB, Ter Riet G.Stability and predictiveness of multiple trigger and episodic viral wheeze in preschoolers. Clin Exp Allergy. 2016 Jun;46(6):837-47.19) Spycher BD, Cochrane C, Granell R, Sterne JAC, Silverman M, Pedersen E, Gaillard EA, Henderson J, Kuehni CE. Temporal stability of multitrigger and episodic viral wheeze in early childhood. Eur Respir J. 2017 Nov 2;50(5):1700014.20) Gokmirza Ozdemir, P, Eker D, Celik V, Beken B, Gurkan H, Yazicioglu M, Sut N. The relationship between arginase genes polymorphisms and preschool wheezing phenotypes. Pediatr Pulmonol. 2020 ….

Species can adapt to climate change by adjusting in situ or by dispersing to new areas, and these strategies may complement or enhance each other. Here, we investigate temporal shifts in phenology and spatial shifts in northern range boundaries for 289 Lepidoptera species by using long-term data sampled over two decades. While 40% of the species neither advanced phenology nor moved northward, nearly half (47%) -used one of the two strategies. The strongest positive population trends was observed for the minority of species (13%) that both advanced flight phenology and shifted their northern range boundaries northward. We show that, for Boreal Lepidoptera, a combination of phenology and range shifts is the most viable strategy under a changing climate. Effectively, this may divide species into winners and losers based on their propensity to capitalize on this combination, with potentially large consequences on future community composition.

Freshwater shrimp is an extremely rich species group with a long and problematic taxonomic history, attributed to its wide distribution, numerous species and similar morphology. Shrimp diversity and species identification is utmost important for fisheries management. However, identification based on morphological characteristics is difficult and complex for a non-specialist to perform. The water system of Henan Province is relatively abundant, but there are few investigations of freshwater shrimps and no description of molecular features. The aim of this study was to uncover the species diversity and phylogenetic of freshwater shrimp in Henan province by combining morphological identification and molecular species delimitation (barcoding gene: COI gene). About 1,200 freshwater shrimp samples from 46 sampling sites were collected for preliminary traditional morphological identification, 222 samples of these were been further microscopic examination and molecular delimitation. Here we used tree based method (NJ, ML) and distance based method (ABGD, bPTP) mainly to define species, detect the cryptic species and assess the validity of the barcoding in molecular. Comprehensive morphological identification and molecular delimitation results, there were 9 effective species and more than one cryptic species of freshwater shrimp in the province and moreover all of them can be identified by DNA barcoding. The results of morphological identification and molecular identification show high consistency, which proves the high efficiency in freshwater shrimp species identification of the DNA barcoding and the presence of cryptic species.

Aim: Cognitive impairment is frequently observed in epileptic patients. It has been seen that not only epilepsy but antiepileptic drugs also impair cognitive functions. The present study was undertaken to assess the effect of three anticonvulsants Levetiracetam (60 mg/kg, p.o.), Vigabatrin (100 mg/kg, p.o.) and Sodyum Valproat (50 mg/kg, p.o.) on anxiety and depression on animal models of rats. Materials and methods: Elevated plus maze (EPM) and Forced swimming test- Porsolt tests (FST) were carried out after 12th weeks of the lifes of rats those that took the three anticonvülsion therapy administration. Results: The results of the present study indicate that none of the three antikonvülsan drugs taken in childhood period impairs anxiety and depression in adult hood. Conclusion: To conclude, long term administration of Levetiracetam, Vigabatrin and Sodyum Valproat have no effect on the anxiety and depression at adulthood time if epilepsy does not exist.

Diffusible iodine-based contrast-enhanced Computed-Tomography (diceCT) visualizes soft-tissue from microCT (µCT) scans of specimens to uncover internal features and natural history information without incurring physical damage via dissection. Unlike hard-tissue imaging, diceCT datasets are currently limited to a few individual specimens and taxonomically underrepresented. To initiate best practices for diceCT in a non-model group, we outline a guide for staining and high-throughput µCT scanning in snakes. We scanned the entire body and one region of interest (i.e., head) for 23 specimens representing 23 species from the clades Aniliidae, Dipsadinae, Colubrinae, Elapidae, Lamprophiidae and Viperidae. We generated 82 scans that include 1.25% Lugols iodine stained (soft tissue) and unstained (skeletal) data for each specimen. We found that duration of optimal staining time increased linearly with body size; head radius was the best indicator. Post-reconstruction of scans, optimal staining was evident by evenly distributed grayscale values and clear differentiation among soft-tissue anatomy. Under and over stained specimens produced poor contrast among soft-tissues, which was often exacerbated by user bias during “digital dissections” (i.e., segmentation). Regardless, all scans produced usable data from which we assessed a range of downstream analytical applications within ecology and evolution (e.g., predator-prey interactions, life history, and morphological evolution). Ethanol de-staining reversed the known effects of iodine on the exterior appearance of physical specimens, but required substantially more time than reported for other de-staining methods. We discuss the feasibility of implementing diceCT techniques for a new user, including approximate financial and temporal commitments, required facilities, and potential effects of staining on specimens. We present the first high-throughput workflow for full-body skeletal and diceCT scanning in snakes, which can be generalized to any elongate vertebrates, and increases publicly available diceCT scans for reptiles by an order of magnitude.

The vegetation in the desert riparian zone represents a critical barrier in the maintenance of the ecosystem’s balance. However, in recent years, the vegetation degradation of the riparian zone have seriously hindered economic development and ecological environment conservation. Based on a field investigation and literature, the mechanisms of vegetation degradation in the lower reaches of the Ugan River are discussed in this study through the analysis of plant coverage, diversity, substitution rate, distribution pattern, grey correlation analysis, and the relationship with groundwater depth. The results showed that the vegetation coverage in this region is relatively low when the water depth exceeds 4 meters. Furthermore, the Shannon-Wiener index, the Simpson index and the Pielou index have all decreased with increases in water depth. Woody plants are the main species maintaining the ecological balance of the region with an aggregation distribution pattern. The degradation of vegetation is the result of the lack of water sources and intense water consumption caused by human activities(especially agricultural). To promote the ecological balance and vegetation restoration, the relative optimal water depth range can be maintained within 2 to 5 meters and proper control human activities.besides the degraded vegetation can gradually be restored using point and surface (i.e., flowering in the center and spreading to the surrounding areas).

The world is currently facing the COVID-19 pandemic that is taking a heavy toll on several countries. While many infected patients have a good prognosis, in some cases the progression can be serious and even lead to death. The commonly seen complications are a cytokine storm and multi-organ failure that require intensive care. The mortality of critically ill patients depends on age (> 65 years), sex (male) or co-morbidities. There is an urgent need to discover a biomarker to identify early on patients at risk of developing serious complications, and to find an effective treatment that could prevent disease progression and critical states. Recent investigations have pointed to the possible contribution of intestinal dysbiosis to the pathophysiology of COVID-19. Herein, we hypothesize that butyrate, a short-chain fatty acid produced by the gut microbiota, can prevent immune system activation and disease progression.

Western equine encephalitis virus (WEEV) can cause lethal encephalitis in humans and equines and represents a serious public health threat in many countries. Therefore, development of efficient vaccines against WEEV remains an important challenge in the field of disease control. This study described for the first time successful production of WEEV virus-like particles (VLPs) in insect cells using recombinant baculoviruses. This well-established expression system is very suitable for production of WEEV VLPs. The immune experiment herein in mice showed that the VLPs formulated with 206-adjuvant were responsible for the stronger-VLP-specific cellular immune response, and were able to induce the secretion of IL-2, IL-4, IFN-γ and production of high titer antibodies that can effectively neutralize the WEEV pseudoviruses. The WEEV VLPs from insect cells could provide a new, safe, non-replicating and effective vaccine candidate against WEEV infections.

Under investigation is a (3+1)-dimensional generalized breaking soliton equation in nonlinear media. The interaction solution between lump wave and N-soliton (N = 2,3,4) are derived. The interaction solution between lump wave and periodic waves is also studied. Breather-wave and multi-wave solutions are obtained. The dynamical behavior is demonstrated by some 3D graphics and density plots. By means of mathematical induction, we also obtain the exact solution containing three arbitrary functions.

An agricultural watershed, Cole Farm, was established as the newest of the three subcatchments in the Susquehanna Shale Hills Critical Zone Observatory (SSHCZO) in 2017. The catchment contains mostly pasture and crops, with a small portion of deciduous forest. The observations in Cole Farm afford an opportunity to test the spatially distributed land surface hydrologic model, Flux-PIHM, in farmland for the first time. In this study, we calibrated the model to only discharge and groundwater level observations at Cole Farm, but it’s able to capture the variations and magnitudes of soil moisture, latent heat (LE) and sensible heat (H) fluxes. Modeled soil moisture on the ridge top matched the observations well, but modeled soil moisture in the mid-slope differed from observations likely due to the existence of fragipan in the soil column. Flux-PIHM reproduced the seasonality and diurnal variations of watershed-average evapotranspiration (ET), sensible heat flux (H), though modeled ET in summer is about 25% greater than tower ET. To study the impact of land cover on hydrology, we imposed two different LAI forcings to the model: spatially distributed versus uniform LAI. Spatially distributed LAI produced higher ET and lower soil moisture in the forested part of the watershed due to higher LAI of deciduous forest in comparison to crops and pasture. But the impact of different LAI forcings on discharge was small. We further compared the water budget simulated by Flux-PIHM in the agricultural watershed (Cole Farm) to a forested watershed (Shale Hills). Flux-PIHM simulated less discharge and higher transpiration and bare soil evaporation in the Cole Farm watershed relative to Shale Hills watershed. Our work shows that with a few key observations, Flux-PIHM can be calibrated to simulate agricultural watershed hydrology, but spatially distributed LAI and soils data are needed to capture the spatial variations in soil moisture and ET.

Objective: Caesarean delivery rates continue to rise globally the reasons for which are poorly understood. We aimed to characterize attributable factors for increasing caesarean delivery rates over a 30-year period within our health network. Design: Observational cohort study. Setting: Two hospitals (large tertiary referral hospital and metropolitan hospital) in Sydney, Australia, across two time periods: 1989-1999 and 2009-2016, between which the caesarean delivery rate increased from 19% to 30%. Participants: All women who had a caesarean delivery after 24 weeks gestation Methods: Data were analysed using multiple imputation and robust Poisson regression to estimate the changes in the caesarean delivery rate attributable to maternal and clinical factors. Main outcome measures: Caesarean delivery. Results: Fifty-six percent of the increase in the rate of caesarean delivery was attributed to changes in the distribution of maternal factors including maternal age, body mass index, parity and history of previous caesarean delivery. When changes in the obstetric management of multiple gestation, malpresentation and preterm singleton birth were considered, 66% of the increase in caesarean rate was explained. When pre-labour caesarean deliveries for maternal choice, suspected fetal compromise, previous pregnancy issues and suspected large fetus were excluded, 78% of the increase was explained. Conclusions: Most of the steep rise in the caesarean delivery rate from 19% to 30% is attributable to changes in maternal demographic and clinical factors.

Paediatric multisystem inflammatory syndrome: temporally associated with SARS-COV-2 (PIMS-TS) is a well described rare but severe COVID-19 related syndrome. PIMS-TS have been reported in children from geographical areas of high COVID-19 infection. Most children with PIMS-TS require management in an intensive care unit with variable respiratory involvement. Adults recovering from COVID-19 infection have been reported to suffer from respiratory morbidity but such outcomes are unknown in children. We present the first report of normal short term respiratory outcomes as measured by spirometry in children with SARS-COV-2 antibody positive, PIMS-TS syndrome managed at a specialist children’s hospital in the UK.

Aim: The aim of this study was to assess the efficacy of pre-operative axillary ultrasonography (AUS) and pre-operative axillary fine-needle aspiration biopsy (FNAB) from suspicious lymph nodes in clinically node-negative breast cancer to compare with radiologically positive and sentinel lymph node biopsy (SLNB) positive involvement. Method: Clinically node-negative early-stage breast cancer patients were included in the study. These patients under went pre-operative AUS examination, suspicious lymph nodes were evaluated with FNAB. AUS-FNAB results were compared with those of SLNB or of axillary dissection. Results: Of 181 patients undergoing AUS, 32 were reported to have axillary metastasis, 25 suspicious and 124 benign nodes. The suspicious group underwent FNAB examination and metastasis was found in 9 of them. The sensitivity of AUS-FNAB was found to be 64.06%, specificity 100%, positive predictive value 100% and negative predictive value (NPV) 83.5%. False negativity rate (FN) of this method was 16,4%. Lymphovascular invasion and tumor size were found statistically significant factors for false negativity. Conclusion:It was concluded that axillary AUS-FNAB with its high NPV, low FN rate, may be a clinical alternative to SLNB for early stage breast cancer patients.

Rationale, aims, and objectives The current strategy of searching for an effective drug to treat COVID-19 relies mainly on repurposing existing therapies developed to target other diseases. There are currently more than four thousand active studies assessing the efficacy of existing drugs as therapies for COVID-19. The number of ongoing trials and the urgent need for a treatment poses the risk that false-positive results will be incorrectly interpreted as evidence for treatments’ efficacy and a ground for drug approval. Our purpose is to assess the risk of false-positive outcomes by analyzing the mechanistic evidence for the efficacy of exemplary candidates for repurposing, estimate false discovery rate, and discuss solutions to the problem of excessive hypothesis testing. Methods We estimate the expected number of false-positive results and probability of at least one false-positive result under the assumption that all tested compounds have no effect on the course of the disease. Later, we relax this assumption and analyze the sensitivity of the expected number of true-positive results to changes in the prior probability (π) that tested compounds are effective. Finally, we calculate False Positive Report Probability and expected numbers of false-positive and true-positive results for different thresholds of statistical significance, power of studies, and ratios of effective to non-effective compounds. We also review mechanistic evidence for the efficacy of two exemplary repurposing candidates (hydroxychloroquine and ACE2 inhibitors) and assess its quality to choose the plausible values of the prior probability (π) that tested compounds are effective against COVID-19. Results Our analysis shows that, due to the excessive number of statistical tests in the field of drug repurposing for COVID-19 and low prior probability (π) of the efficacy of tested compounds, positive results are far more likely to result from type-I error than reflect the effects of pharmaceutical interventions.

Concomitant surgery on the aortic arch with hypothermic cardiac arrest in the setting of heart transplantation (HTX) is extremely rare. A 67-year-old woman who suffered from ischemic cardiomyopathy was evaluated for HTX. Computed tomography showed diffuse soft and hard atheromatous plaques of the entire aorta. Upon allocation of an appropriate donor organ, the ascending aorta and the proximal aortic arch were replaced using hypothermic cardiac arrest at 28℃ prior to arrival of the donor heart and without clamping of the diseased recipient aorta. After uncomplicated postoperative course the patient was recovered without neurological complications.

Aim The aim of this study is to model the past, current and future distribution of J. phoenicea s.s., J. turbinata and J. canariensis, based on bioclimatic variables using a maximum entropy model (MaxEnt) in the Mediterranean and Macaronesian regions. Location Mediterranean and Macaronesian Taxon Cupressaceae, Juniperus Methods Data on the occurrence of the J. phoenicea complex was obtained from the GBIF, the literature, herbaria, and the authors’ field notes. The bioclimatic variables were obtained from the WorldClim database (http://worldclim.org/) and Paleoclim (http://www.paleoclim.org/). The climate data related to species localities were used for predictions of niches by implementation of MaxEnt and we evaluated the model with ENMeval. Results The potential niches of Juniperus phoenicea during the LIG, LGM and MH covered 30%, 10% and almost 100%, respectively, of the current potential niche. Climate warming could reduce potential niches by 30% and 90% in scenarios RCP2.6 and RCP8.5, respectively. The potential niches of Juniperus turbinata had a broad circum-Mediterranean and Canarian distribution during the LIG and the MH, extending its distribution during the LGM when it was found in more areas than at present; the predicted warming in scenario RCP2.6 and RCP8.5 could reduce the current potential niche by 30% and 50%, respectively. The model did not find suitable niches for J. canariensis during the LIG and the LGM, but during the MH its potential niche was 30% larger than at present. The climate warming scenario RCP2.6 indicates a reduction of the potential niche by 30%, while RCP8.5 does so by almost 60%. Main conclusions This research can provide information to increase the protection of the juniper forest and to try to counteract the phenomenon of local extinctions caused by anthropic pressure and climate changes.

Soil acidification is one of the major soil degradation phenomenon in tropical and subtropical region, which cause reductions in soil fertility, particularly potassium (K), and declines in crop yield. However, it remains unclear whether and how the status of K in soils and crops changes with the application of lime to alleviate soil acidification. Six treatments of long-term experiments (started 1990) in subtropical region were carried out. Regardless of fertilization regime, lime addition markedly increased grain and straw yields compared to those yields without lime application. Lime addition also led to significant decreases in the apparent K balances compared to soils without lime application. The agronomic K efficiency and partial factor productivity of K fertilizer both significantly increased after lime application. Lime addition reduced the soil exchangeable K (EK) content and stock, while increased soil non-exchangeable K (NEK) content and stock. Redundancy analysis showed that K input, lime, pH, and exchangeable calcium all significantly affected the K in soil and crops. Path analysis showed that lime indirectly influenced soil K (EK and NEK) by directly affecting soil pH, exchangeable calcium, K uptake and apparent K balances. These results suggest that lime addition is a viable strategy for improving crop yields and K fertilizer efficiency in degraded soils caused by acidification. Lime significant increased K uptake which lead to decreased soil EK content and stock. Additional, lime also increased soil NEK content and stock which was regulated by soil pH, exchangeable calcium, and crop growth.

Introduction:It has been known that there is a complex interaction between asthma and cardiovascular physiology.Some investigations on echocardiography and electrocardiography(ECG) in asthmatic patients revealed many findings such as pulmonary hypertension(PHT) and arrhythmia.In this study,we aimed to perform tissue doppler imaging(TDIE) and conventional echocardiographic(CEI) assessment with many indexes of arrhythmia on electrocardiography(ECG) in asthmatic patients.Methods:A total of 89 patients,63 female(70.8%) and 26 male(29.2%),was included in this study.Patients were divided into three groups and then each group was separated in two 2 groups as mild-moderate and severe asthma.Results:There is no difference among groups with respect to age,gender and anthropometric data and no difference between groups with respect to indexes of arrhythmia on ECG(p> 0.05).It was determined that ventricular outflow systolic velocity recordings at aortic and pulmonary valve were similar(p> 0.05).MAPSE,TAPSE and both ventricular diastolic velocities on CEI were similar between groups,except for left ventricular A wave velocity which was higher in severe asthmatic patients(p< 0.05).No difference between groups was detected in left atrium(LA) TDIE diastolic velocities(p> 0.05).Investigation of time intervals of both ventricular diastolic filling velocities(e’ and a’) at the mitral lateral,septal and tricuspid lateral annulus revealed significant difference at Pa’m- 3 and Pa’s- 3 intervals based on TDEI(p<0.05).Investigation of the LA volumes determined that only maximal volume of the LA was higher in severe asthmatic patients(p< 0.05).However, there is no significant difference between LA-VpreA and LA-Vmin(p> 0.05).Conclusions:Based on these results, it can be suggested that LA mechanical functions and intra-atrial LA electromechanical durations were impaired in severe asthmatic patients.

Aneurysms of the sinus of Valsalva are rare, with dissecting aneurysms of the sinus of Valsalva that extend into the interventricular septum being even more rare. This report describes a young patient with syphilis and a quadricuspid aortic valve who experienced a spontaneously dissecting aneurysm of the sinus of Valsalva and the basal interventricular septum.

Introduction: Several homeostatic changes like an increase in sympathoadrenal response and oxidative stress occur in hypoglycemia. As a result of these findings, an increase in inflammation and pre-atherogenic factors is observed and these changes may lead to endothelial dysfunction. Aim: Our study aims to reveal possible cardiac risks (systolic-diastolic functions and endothelial dysfunctions) in patients who have applied to the emergency department with hypoglycemia. Methods: This cross-sectional, case-control study included 46 hypoglycemia patients who admitted to the emergency with symptoms compatible with hypoglycemia and diagnosed with hypoglycemia and 30 healthy volunteers. All patients were evaluated with baseline echocardiography, tissue-doppler imaging(carotid and brachial artery). Also, the fasting blood tests of the patients referred to the internal medicine department were examined. Results: There were no differences between the groups regarding age, weight, body mass index, and systolic blood pressure. Total cholesterol, LDL, HDL, Vitamin B12, TSH, and fasting blood glucose levels were similar in the groups’ blood tests (all p values>0.05). We observed a statistically significant decrease in diastolic dysfunction parameters: E/A and E/e’ ratios (respectively, p=0.020 and 0.026). It was shown that insulin resistance was influential in forming these considerable differences. The patient group observed that the carotid intima-media thickness was more remarkable(p=0.001), and the brachial flow-mediated dilatation value was smaller(p=0.003), giving an idea about endothelial functions.

Described is an atypical presentation of a rare condition. It highlights the importance of thorough algorithm of medical and family history, physical examination, appropriate investigations and perioperative workup and for surgery. This case raises the awareness that a lateral neck mass (or lateral ectopic thyroid mass) can be benign.

This report describes the case of a 53-year-old man with SARS-CoV-2 infection and occurrence of complete unilateral sensorineural hearing loss, adding new evidence to the association between COVID-19 and hearing loss. Whether this is the result of endothelial cell dysfunction in the cochlea or central auditory pathways remains unclear.