Predation can take unexpected turns. For instance, various invertebrate species - most commonly spiders - may prey on tetrapods. Here, we report observations of spiders (Sparassidae, Olios sp.) preying on amphibians (Hyperoliidae, Heterixalus andrakata) in north-eastern Madagascar. To do so, the spiders built highly-specialized traps by weaving two leaves together. Four cases by different individuals of the same species show that spiders hide at the rear end of the trap. One case reports the feeding on a small frog caught inside the trap. Previous reports on amphibian predation by spiders describe opportunistic and indiscriminate predation behaviour by generalist ground-dwelling or aquatic spiders. The only more targeted cases concern large orb-weaver spiders building large webs that may serve as an effective trap for small vertebrates, but those only make up a small percentage of prey compared to insects. In contrast, the novel traps type reported here seems to be solely targeted at catching amphibians seeking shelter during the daytime. We thus report systematic trapping of amphibian by spiders, a newly recorded behaviour.

Background: Although the importance of ectopic lymphoid tissues (eLTs) in the pathophysiology of nasal polyps (NPs) is increasingly appreciated, the mechanisms underlying their formation remain unclear. Objective: To study the role of IL-17A, CXCL13 and lymphotoxin (LT) in eLT formation in NPs. Methods: The expression of CXCL13 and LT as well as their receptors, and the phenotypes of stromal cells in NPs were studied by flow cytometry, immunostaining, and RT-PCR. Purified nasal stromal cells and polyp B cells were cultured and a murine model with nasal type 17 inflammation was established for the mechanistic study. Results: Excessive CXCL13 production was found in NPs and correlated with enhanced IL-17A expression. Stromal cells, with an expansion of CD31-Pdpn+ fibroblastic reticular cell (FRC) type, were the major source of CXCL13 in NPs without eLTs. IL-17A induced FRC expansion and CXCL13 production in nasal stromal cells. In contrast, B cells were the main source of CXCL13 and LTα1β2 in NPs with eLTs. CXCL13 upregulated LTα1β2 expression on polyp B cells, which in turn promoted CXCL13 production from polyp B cells and nasal stromal cells. LTα1β2 induced expansion of FRCs and CD31+Pdpn+ lymphoid endothelial cells, corresponding to the phenotypic characteristic of stromal cells in NPs with eLTs. IL-17A gene knockout, and CXCL13 and LTβR blockage diminished nasal eLT formation in the murine model. Conclusion: We identified an important role of IL-17A-induced stromal cell remodeling in the initiation, and crosstalk between B and stromal cells via CXCL13 and LTα1β2 in the enlargement of eLTs in NPs.

Reaction-diffusion equations are often used in epidemiological models. In this paper, we generalize the algorithm of Meerschaert and Tadjeran for fractional advection-dispersion flow equations to a coupled system of fractional reaction-diffusion like an equation that arises from vector bourne disease modeling.

COVID-19 in a child with severe aplastic anemiaYunus Murat Akçabelen1, Ayça Koca Yozgat1, Aslı Nur Parlakay2, Nese Yarali11 Department of Pediatric Hematology, Ankara City Hospital Children’s Hospital, Turkiye2 Department of Pediatric Infectious Disease, Ankara City Hospital Children’s Hospital, TurkiyeArticle type: Letter to the editörRunning Title: COVID-19 in pediatric aplastic anemiaKey words: COVID-19, children, aplastic anemiaDisclosures: noneWord counts: 625

A document by Vladimir Giménez Rivera, written on Authorea.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is a newly identified coronavirus which has spread from China to the rest of the world causing the pandemic coronavirus disease 19 (COVID-19). It has fatality rate that floats from 5 to 15% and the symtoms are fever, cough, myalgia and/or fatigue up to dyspnea, responsible for hospitalization and in most of the cases of artificial oxygenation. In the attempt to understand how the virus spreads and how to pharmacologically abolish it, it was highlighted that SARS-CoV2 infects human cells by means of angiotensin converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2) and 3-chymotrypsin-like protease (3CLpro), also known as Mpro. Once bound to its receptor ACE2, the other two proteases, in concert with the receptor-mediated signaling, allow virus replication and spread throughout the body. Our attention has been focused on the role of ACE2 in that its blockade by the virus increases Bradykinin and its metabolites, well known to facilitate inflammation in the lung (responsible for cough and fever), facilitate both the coagulation and complement system, three mechanisms that are typical of angioedema, cardiovascular dysfunction and sepsis, pathologies which symptoms occur in COVID-19 patients. Thus, we propose to pharmacologically block the kallicrein-kinin system upstream bradykinin and the ensuing inflammation, coagulation and complement activation by means of lanadelumab, which is a clinically approved drug for hereditary angioedema.

A novel bat coronavirus (2019-nCoV) caused an outbreak of infectious pneumonia termed COVID-19 in the world. This reminds us of another notorious bat coronavirus, SARS-CoV, which mysteriously broke out in China 17 years ago and killed nearly 800 people worldwide. A key to its efficient human attack is adopting angiotensin-converting enzyme 2 (ACE2) as the receptor. The relationship between 2019-nCoV and SARS-CoV has aroused much public concern. To our surprise, we found that the two CoV lineages may frequently exchange their genetic materials through homologous recombination. Particularly 2019-nCoV might thereby acquire the receptor-binding domain from the SARS-CoV clade, enabling it to make use of ACE2 as well and thus spread rapidly in humans. Our findings suggest the accomplice role of a virus of SARS-CoV clade in COVID-19 and warn of the possible emergence of more mosaic CoVs capable of launching severe epidemic.

Background and Purpose: The emergence of new synthetic cathinones continues to be a matter of public health concern. In fact, they are quickly replaced by new structurally related alternatives. The main goal of the present study was to characterize the pharmacological profile, the psychostimulant and rewarding properties of novel synthetic cathinones differing in its amino terminal substitution. Experimental Approach: Rat brain synaptosomes were used for [3H]dopamine uptake experiments. HEK293 transfected cells (hDAT, hSERT, hOCT; human dopamine, serotonin and organic cation transporter, respectively) were also used for [3H]monoamine uptake and transporter binding assays. Molecular docking allowed to investigate the effect of the amino substitutions on the biological activity. Locomotor activity experiments and conditioned place preference paradigm were used in order to study the psychostimulant and rewarding effects in mice. Key Results: All compounds tested are potent inhibitors of DAT with very low affinity for SERT, hOCT-2 and -3, and their potency inhibiting DAT increased when the amino-substituent expanded from a methyl- to either an ethyl-, a pyrrolidine- or a piperidine-ring. Regarding the in vivo results, all the compounds induced an increase in locomotor activity and possess rewarding properties. Results also showed a significant correlation between predicted binding affinities by molecular docking and affinity constants (Ki) for hDAT. Conclusions and Implications: Our study demonstrated the role of the amino-substituent in the pharmacological profile of novel synthetic cathinones and provides the first evidence that some of them are potent DAT inhibitors and able to induce psychostimulant and rewarding effects in mice.

Abstract The objective of this study was to describe early respiratory outcomes of asymptomatic COVID-19 patients after cardiac surgery. In this retrospective clinical study (case series) we reviewed and analyzed patient clinical data of 25 covid-19 asymptomatic patients that underwent urgent or emergent cardiac surgery between February 29 and April 10, 2020 in Tehran Heart Center Hospital. Median of age was 63 years (IQR, 52-67), Euro SCORE 7.50 (IQR, 6.5-8.5) and body mass index 26.3 (IQR, 22.5-28.6). 68% of patients had one or more comorbidities. Hypertension (56%) was the most common followed by Diabetes type 2 (40%). Off-pump cardiac surgery was done in 4 patients and on-pump on 21 patients with median CPB time of 85 minutes (IQR, 50-147.50). Median anesthesia time was 4.5 hours (IQR, 4-5). Median oxygen index and Fio2 on ventilator were 10 cmH20 (IQR, 9.5-10.5) and 0.64(IQR, 0.60-0.64) respectively. Median pao2/Fio2 was 231(IQR, 184-261). There was one case of extubation failure. The Median intubation time and length of ICU stay were 13 hours (IQR, 9.5-18) and 3 days (IQR, 2-4) respectively. Overall mortality was 16%. Readmission rate to ICU was 16% with. In this group respiratory outcome was worse with median Pao2/Fio2 84.5 (75-122), oxygen index of 4.38(IQR, 3.77-5.1) and morality rate of 75%. Conclusion: Based on the results of this study, very early post-cardiac surgery respiratory outcomes in asymptomatic COVID-19 patients are apparently smooth; nonetheless, readmission to the ICU is high. Overall respiratory outcomes are poor especially for those who readmitted to ICU.

CONSTANS-LIKE (COL) family members are commonly implicated in light signal transduction during early photomorphogenesis. However, some of their functions remain unclear. Here, we propose a role for COL13 in hypocotyl elongation in Arabidopsis thaliana. We found that COL13 RNA accumulates at high levels in hypocotyls and that a disruption in the COL13 function via a T-DNA insertion or RNAi led to the formation of longer hypocotyls of Arabidopsis seedlings under red light. On the contrary, overexpression of COL13 resulted in the formation of shorter hypocotyls. Using various genetic, genomic, and biochemical assays, we proved that another COL protein, COL3, directly binds to the promoter of COL13, and the promoter region of COL3 was targeted by the transcription factor LONG HYPOCOTYL 5 (HY5), to form an HY5-COL3-COL13 regulatory chain for regulating hypocotyl elongation under red light. Additionally, further study demonstrated that COL13 interacts with COL3, and COL13 promotes the interaction between COL3 and CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1), suggesting a possible COP1-dependent COL3-COL13 feedback pathway. Our results provide new information regarding the gene network in mediating hypocotyl elongation.

Abstract: Background: COVID-19 burst in Wuhan China in December 2019 and soon became a worldwide emergency. To help further understand COVID-19. Here we report the epidemiological, clinical features, potential biomarkers, and CT changes of cases in Wenzhou. Methods:All 64 cases were diagnosed by positive of PCR test. Clinical laboratory tests, CT and treatment were performed in the level 3 of protection. Data and clinical characteristics feature were collected by 4th March. The correlation was analyzed. Results:Most cases were light. The average of latency was 3.4 days, ranged from 1-14. The median age was 44, ranged from 2.2-67; 36 male and 28 female; 59 had fever, 38 with high temperate (>38℃); 45 had respiratory symptoms; 28 had gastrointestinal symptoms; 39 weakness; one asymptomatic case was found. Most with low LC, K+, Na+, OI and high LDH, CRP, D-dimer. Pneumonia, both lungs involvement, ground-glass opacity and consolidation were shown by CTs. Minor had electrocardiography change. Conclusions:The clinical features, abnormality lab indexes and CT characteristics of COVID-19 were like SARS, majored in fever, weakness along with dry cough, diarrhea. LC, LDH could be good biomarkers monitoring progress. The elders, hypertension patients and smokers were more vulnerable. COVID-19 was milder, but more transmissible than SARS. Latency could be up to 14 days without symptoms. CT and PCR shall be both considered in clinical high suspicion. There are still further efforts to be made as to preventing and control the epidemic and the cost in world wild.

Rationale, aims, and objectives: Post-hospitalization follow-up within 30 days following discharge has been shown to positively impact time to readmission, healthcare costs, and patient self-reported adherence and satisfaction. We aimed to improve resident satisfaction with the process of establishing post-hospitalization, primary care provider (PCP) follow-up. Methods: In this quality improvement study we surveyed all internal medicine residents at our institution regarding their satisfaction with the process of establishing PCP follow-up at the time of hospital discharge. A streamlined process was developed and two subsequent interventions were enacted; a dedicated teaching session and distribution of pocket cards outlining the process. Residents were then surveyed following each intervention to assess for impact on overall satisfaction and burden of work. Results: Initially, 77.3% of residents were not satisfied with the process of establishing post-hospitalization PCP follow-up. Following the first intervention there was a trend towards increasing satisfaction rates by 16.7% (p= 0.20), and after the second intervention there was a statistically significant increase in satisfaction rates from baseline by 44% (p= 0.007). There was also a reduction in the feeling of workload burden associated with establishing PCP follow-up from 32% to 25%, and over 67% of participants either agreed or strongly agreed that the workload was not too burdensome. Conclusion: This quality improvement initiative established that resident physicians at our institution previously found the process of establishing PCP follow-up at the time of patient discharge both confusing and burdensome. Through the implementation of our interventions we were able to achieve our aims of improving resident satisfaction.

Summer heat waves are the principal global driver of mortality in reef-building corals. Resilience-based genetic management may increase coral heat tolerance, but it is unclear how temperature responses are regulated at a genomic level and thus how corals may adapt to warming naturally or through selective breeding. Here we combine phenotypic, pedigree, and genomic marker data from colonies sourced from a warm reef on the Great Barrier Reef reproductively crossed with conspecific colonies from a cooler reef to produce combinations of warm and cool purebred and hybrid larvae and juveniles. Intra-population breeding created significantly greater genetic diversity across the coral genome and maintained diversity in key regions associated with heat tolerance and fitness. High-density genome-wide scans of single nucleotide polymorphisms (SNPs) identified alleles significantly associated with offspring reared at 27.5°C (87 – 2,224 loci), including loci putatively associated with proteins involved in responses to heat stress (cell membrane formation, metabolism, and immune responses). Underlying genetics explained 43% of PCoA variation in juvenile survival, growth, and bleaching responses at 27.5°C and 31°C between the multilocus genotypes. Genetic marker contribution to total variation in fitness traits (narrow-sense heritability) were high for survival but not for growth and bleaching in juveniles, with heritability of these traits influenced more at 31°C relative to 27.5°C. Using only a limited number of crosses, the mechanistic understanding presented here demonstrates that allele frequencies are affected by one generation of selective breeding, key information for the assessments of genetic intervention feasibility and modelling of reef futures.

Mosquitoes utilize their sense of smell to locate prey and feed on their blood. Repellents interfere with the biochemical cascades that detect odors. Consequently, repellants are highly effective and resource-efficient alternatives for controlling the spread of mosquito-borne illnesses. Unfortunately, the discovery of repellents is slow, laborious and error-prone. To this end, we have improved the speed and accuracy of repellant discovery by constructing a whole-cell biosensor for accurate detection of mosquito behavior-modifying compounds such as repellants. We genetically engineered Pichia pastoris to express the olfactory receptor co-receptor (Orco) of Anopheles gambiae mosquitoes. This transmembrane protein behaves like a cationic channel upon activation by stimulatory odorants. When the engineered Pichia cells are cultured in calcium-containing Hank’s buffer, induction of the medium with a stimulatory odorant results in influx of calcium ions into the cells, and the stimulatory effect is quantifiable using the calcium-sequestering fluorescent dye, fluo-4-acetoxymethyl ester. Moreover, the stimulatory effect can be titrated by adjusting either the concentration of calcium ions in the medium or level of induction of the stimulatory odorant. Subsequent exposure of the activated Pichia cells to a repellant molecule inhibits the stimulatory effect and quenches the fluorescent signal, also in a titratable manner. Significantly, the modular architecture of the biosensor allows easy and efficient expansion of its detection range by co-expressing Orco with other olfactory receptors. The high-throughput assay is also compatible with robotic screening infrastructure, and our development represents a paradigm change for the discovery of mosquito repellants.

Background Pediatric solid tumors require coordinated multidisciplinary specialist care. However, expertise and resources to conduct multidisciplinary tumor board (MDTB) meetings are lacking in low- and middle-income countries (LMICs). We aimed to profile practices and perceptions on MDTBs among pediatric solid tumor units (PSTUs) in Southeast Asian LMIC countries. Methods Using online survey forms, availability of specialty manpower and MDTBs among PSTUs was first determined. From the subset of PSTUs with MDTBs, 1 pediatric surgeon and 1 pediatric oncologist from each center were queried using 5-point Likert scale questions adapted from published questionnaires. Results In 37/46 (80.4%) identified PSTUs, pediatric-trained oncologists, surgeons, radiologists, pathologists, radiation oncologists, nuclear medicine physicians and nurses were available in 94.6%, 91.9%, 54.1%, 40.5%, 29.7%, 13.5% and 81.1% of PSTUs, respectively. Availability of pediatric-trained surgeons, radiologists and pathologists were significantly associated with existence of MDTBs (p=0.037, 0.005, 0.022 respectively). Among 43/48 (89.6%) respondents from 24 PSTUs with MDTBs, 90.5% of oncologists reported >50% oncology-dedicated workload versus 22.7% of surgeons. Views on benefits and barriers did not significantly differ between both groups. Majority agreed MDTBs helped improve accuracy of treatment recommendations and team competence. Complex cases, insufficient radiology and pathology preparation, and need for supplementary investigations, were the top barriers. Conclusions Availability of pediatric-trained subspecialists was a significant prerequisite for pediatric MDTBs. Most PSTUs lacked pediatric-trained pathologists and radiologists. Correspondingly, gaps in radiographic and pathological diagnoses were the commonest limitations. Greater emphasis on holistic multidisciplinary subspecialty development is needed to advance pediatric solid tumor care in Southeast Asia.

References 1. Wang H, Li T, Barbarino P, Gauthier S, Brodaty H, Molinuevo JL, Xie H, Sun Y, Yu E, Tang Y, Weidner W. Dementia care during COVID-19. Lancet. 2020;395(10231):1190.2. Caraci F, Sultana J, Drago F, Spina E. Clinically relevant drug interactions with anti-Alzheimer’s drugs. CNS & Neurological Disorders-Drug Targets. 2017;16(4):501-13.3. University of Liverpool. COVID-19 Drug Interactions. 2020. https://www.covid19-druginteractions.org. Accessed 21 April, 2020.4. Pytliak M, Vargová V, Mechírová V. Drugs and hypoglycemia. Hypoglycemia–causes and occurrences. Shanghai: InTechOpen. 2011:131-48.5. Pasqualetti G, Tognini S, Calsolaro V, Polini A, Monzani F. Potential drug–drug interactions in Alzheimer patients with behavioral symptoms. Clinical Interventions in Aging. 2015;10:1457.

Anomalous origin of the left circumflex artery (LCA) arising from the right coronary sinus was observed in a 45 year-old man with aortic root aneurysm. Valve-sparing aortic root replacement (VSARR) was decided despite the subannular course of the LCA. A modified Tirone David procedure was performed with specific consideration for distribution of the proximal suture line due to the peri-aortic and subannular course of the LCA. Due to the risk of LCA injury, a coronary artery bypass grafting was performed using the left internal thoracic artery to secure the perfusion of the LCA. The challenging association of aortic root aneurysm and anomalous origin and course of the LCA was managed successfully during VSARR.

AIMS To report the major characteristics and clinical outcomes of COVID-19 patients treated with ACE inhibitors and ARBs and compare the different effects of the two drugs for outcomes of COVID-19 patients. METHODS This is a retrospective, two-center case series of 198 consecutive COVID-19 patients with a history of hypertension. RESULTS Among 198 patients, 58 (29.3%) and 16 (8.1%) were on were on ARB and ACEI, respectively. Patients who were on ARB or ACEI/ARB had a significantly lower rate of severe illness and ARDS when compared with patients treated with ACEI alone or not receiving RAAS blocker (P＜0.05). The Kaplan-Meier survival curve showed that patients with ARB in their antihypertensive regimen had a trend towards a higher survival rate when compared with individuals without ARB (adjusted hazard ratio, 0.27; 95% CI, 0.07-1.02; P=0.054). The occurrence rates of severe illness, ARDS, and death were similar in the two groups regardless of receiving ACEI. The Cox-regression analysis to compared ACEI vs. ARB groups showed a significantly lower mortality rate in the ARB group (adjusted hazard ratio, 0.03; 95% CI, 0.00-0.58; P=0.02). CONCLUSIONS Our data may provide some evidence of using ARB, but not ACEI, was associated with a reduced rate of severe illness and ARDS, indicating their potential protective impact in COVID-19. Further large sample sizes and multiethnic populations are warranted to confirm our findings.

Background The aim was to describe the profile of Head and Neck Cancers (HNC) at a referral centre in South Africa. Methods Records from January 2015 to December 2017 were reviewed. Variables analysed were site, histologic type, age, sex, HIV status, p16 status, treatment intent/ modality, and the Eastern Cooperative Oncology group performance (ECOG). Results Of 854 patients, 71% were male. Median age was 58. Smoking was a risk factor in 86.3% (n=737) and alcohol in 74.2% (n=634). 53.86% (n=460) and 27.17% (n=232) had ECOG scores of 1 and 2 respectively. 9% (n=56) were HIV positive. 167 had oropharyngeal primaries, and 9.58% (n=16) were p16-positive. 53.87% (n=466) had locally advanced disease, and 47.42% (n=405) received palliative treatment. Conclusion At this centre, HNC affects older adult males of lower socioeconomic status, who often smoke and drink and present with locally advanced disease, requiring palliative oncologic care. HPV and HIV play a minor role.

Objective: (1) Demonstrate how machine learning can be used for prediction modeling by predicting the treatment patients with T1-2, N0-N1 Oropharyngeal Squamous Cell Carcinoma receive. (2) Assess disparities in the treatment of this population. Design: Retrospective cohort. The data was split into 80/20 distribution for training and testing, respectively. Machine learning algorithms were explored for development. Area Under the Curve, accuracy, precision, and recall were calculated for the final model. The permutation feature scores highlight significant variables within the model. Setting: National Cancer Database. Participants: Adults diagnosed with T1-2, N0-N1 Oropharyngeal Squamous Cell Carcinoma from 2004 to 2013 were eligible Main Outcome Measure: Primary treatment modality Results: Among the 19,111 patients in the study, the mean (standard deviation) age was 61.3 (10.8) years, 14,034 (73%) were male, and 17,292 (91%) were white. Surgery was the primary treatment in 9,533 (50%) cases, and radiation in 9,578 (50%) cases. The final model yielded an Area Under the Curve of 78% (95% CI, 77% to 79%), accuracy of 71%, precision of 72%, and recall of 71%. The T-stage, primary site, N-stage, grade, and type of treatment facility were impactful variables included in the model. Conclusion: Machine learning was used to predict primary treatment modality for T1-2, N0-N1 Oropharyngeal Squamous Cell Carcinoma. This study demonstrates how machine learning can be used for prediction modeling. The results also suggest treatment is influenced by clinical staging and type of treatment facility.

Key Points- Congenital anosmia is usually associated with Kallmann syndrome, which is characterized by hormonal abnormalities such as hypogonadotropic hypogonadism.- On very rare occasions, an isolated congenital anosmia presents as olfactory bulb agenesis without this associated syndrome.- In previous studies of such cases, diagnosis is usually based on the absence of an olfactory bulb on structural MRI, rather than on objective functional measures.- Simultaneous functional MRI and olfactory event-related potential recordings can provide highly objective evidence of olfactory function.- We examined both structural and functional MRI and olfactory event-related potential data to diagnose isolated congenital olfactory bulb agenesis, gaining objective evidence of olfactory function.

Currently as of May 2020, there are more than 8 potential candidate vaccines against COVID19 in clinical evaluation and another 100 in preclinical evaluation. Considering the governing rules and regulations with respect to non-clinical and clinical evaluations, it may take around 5-6 months at the earliest to have an efficacious COVID 19 vaccine. The question lies ‘DO WE HAVE THAT MUCH TIME?’ The challenges faced today not only have implications to the public health but also the masked social and economic implications as well. Hence, it is imperative to have a Blitz Krieg solution against COVID19.

A 24-year-old male presented with radiating back pain and progressive neurological deficit. MRI revealed spinal epidural tumor at the thoracolumbar junction. He underwent decompression and excisional biopsy. Histopathology and immunohistochemistry identified it as diffuse large B-cell lymphoma. He received chemotherapy and is asymptomatic at one-year follow-up.

Epidermolytic hyperkeratotic EN (epidermal nevus) is a rare variant of EN, which can be congenital or developed later in adulthood. A 23 years old female presented with a pathologic confirmed epidermolytic hyperkeratotic EN. Dermoscopy can be helpful in the diagnosis of EN, but not in differentiating the variant.