Effect of various Na/K ratios in low-salinity well water on growth performance and physiological response of Pacific white shrimp Litopenaeus vannamei

To investigate the influence of sodium to potassium （Na/IO ratios on the growth performance and physiological response of the Pacific white shrimp （Litopenaeus vananmei）, various concentrations of KC1 were added to low-salinity well water （salinity 4） in an 8-week culture trial. Six treatments with NWK ratios of 60：1, 42：1, 33：1, 23：1, 17：1, and 14：1 were replicated in triplicate. The highest weight-gain rate （3 506±48）% and survival rate （89.38±0.88）% was observed in well water with Na/K ratios of 23：1 and 42：1, respectively, while the feed conversion ratio （1.02～0.01）, oxygen consumption, and ammonia-N excretion rate was the lowest in the medium with a Na/K ratio of 23：1. Gill Na＋-K＋-ATPase activity, as an indicator of osmoregulation, peaked in the treatment where the Na/K ratio was 17：1. The total hemocyte count, respiratory burst, and immune-related enzyme activities （ALP, LSZ, PO, and SOD） ofL. vananmei were affected significantly by Na/K ratios （P〈0.05）. After challenged with Vibrio harveyi, the cumulative mortality of shrimp reared in a Na/K ratio of 23：1 （30±14.14）% was significantly lower than the control （75～7.07）%. In conclusion, the addition of K＋ to low-salinity well water in L. vannamei cultures is feasible. Na/K ratios ranging from 23：1 to 33：1 might improve survival and growth. Immunity and disease resistance are also closely related to the Na/K ratio of the low-salinity well water. The findings may contribute to the development of more efficient K^＋ remediation strategies for L. vananmei culture in low-salinity well water.

Gastric neuroendocrine neoplasms type 1: A systematic review and meta-analysis

BACKGROUND To date, the histopathological parameters predicting the risk of lymph node (LN) metastases and local recurrence, associated mortality and appropriateness of endoscopic or surgical resection in patients with gastric neuroendocrine neoplasms type 1 (GNENs1) have not been fully elucidated. AIM To determine the rate of LN metastases and its impact in survival in patients with GNEN1 in relation to certain clinico-pathological parameters. METHODS The PubMed, EMBASE, Cochrane Library, Web of Science and Scopus databases were searched through January 2019. The quality of the included studies and risk of bias were assessed using the Newcastle-Ottawa Scale (NOS) in accordance with the Cochrane guidelines. A random effects model and pooled odds ratios (OR) with 95%CI were applied for the quantitative meta-analysis. RESULTS We screened 2933 articles. Thirteen studies with 769 unique patients with GNEN1 were included. Overall, the rate of metastasis to locoregional LNs was 3.3%(25/769). The rate of LN metastases with a cut-off size of 10 mm was 15.3% for lesions > 10 mm (vs 0.8% for lesions < 10 mm) with a random-effects OR of 10.5 (95%CI: 1.4 -80.8;heterogeneity: P = 0.126;I2 = 47.5%). Invasion of the muscularis propria was identified as a predictor for LN metastases (OR: 17.2;95%CI: 1.8-161.1;heterogeneity: P = 0.165;I2 = 44.5%), whereas grade was not clearly associated with LN metastases (OR: 2;95%CI: 0.3-11.6;heterogeneity: P = 0.304;I2 = 17.4%). With regard to GNEN1 local recurrence, scarce data were available. The 5-year disease-specific survival for patients with and without LN metastases was 100% in most available studies irrespective of the type of intervention. Surgical resection was linked to a lower risk of recurrence (OR: 0.3;95%CI: 0.1-1.1;heterogeneity: P = 0.173;I2 = 31.9%). The reported complication rates of endoscopic and surgical intervention were 0.6 and 3.8%, respectively. CONCLUSION This meta-analysis confirms that tumor size ≥ 10 mm and invasion of the muscularis propria are linked to a higher risk of LN metastases in patients with GNEN1. Overall, the metastatic propensity of GNEN1 is low with favorable 5- year disease-specific survival rates reported;hence, no clear evidence of the prognostic value of LN positivity is available. Additionally, there is a lack of evidence supporting the prediction of local recurrence in GNEN1, even if surgery was more often a definitive treatment.

Chronic pancreatitis and the heart disease:Still terra incognita?

BACKGROUND It has been suggested that chronic pancreatitis(CP)may be an independent risk factor for development of cardiovascular disease(CVD).At the same time,it seems that congestive heart failure(CHF)and CP share the responsibility for the development of important clinical conditions such as sarcopenia,cachexia and malnutrition due to development of cardiac cachexia and pancreatic exocrine insufficiency(PEI),respectively.AIM To explore the evidence regarding the association of CP and heart disease,more specifically CVD and CHF.METHODS A systematic search of MEDLINE,Web of Science and Google Scholar was performed by two independent investigators to identify eligible studies where the connection between CP and CVD was investigated.The search was limited to articles in the English language.The last search was run on the 1st of May 2019.The primary outcomes were:(1)Incidence of cardiovascular event[acute coronary syndrome(ACS),chronic coronary disease,peripheral arterial lesions]in patients with established CP;and(2)Incidence of PEI in patients with CHF.RESULTS Out of 1166 studies,only 8 were eligible for this review.Studies regarding PEI and CHF showed an important incidence of PEI as well as associated malabsorption of nutritional markers(vitamin D,selenium,phosphorus,zinc,folic acid,and prealbumin)in patients with CHF.However,after substitution of pancreatic enzymes,it seems that,at least,loss of appetite was attenuated.On the other side,studies investigating cardiovascular events in patients with CP showed that,in CP cohort,there was a 2.5-fold higher incidence of ACS.In another study,patients with alcohol–induced CP with concomitant type 3c diabetes had statistically significant higher incidence of carotid atherosclerotic plaques in comparison to patients with diabetes mellitus of other etiologies.Earlier studies demonstrated a marked correlation between the clinical symptoms in CP and chronic coronary insufficiency.Also,statistically significant higher incidence of arterial lesions was found in patients with CP compared to the control group with the same risk factors for atherosclerosis(hypertension,smoking,dyslipidemia).Moreover,one recent study showed that PEI is significantly associated with the risk of cardiovascular events in patients with CP.CONCLUSION Current evidence implicates a possible association between PEI and malnutrition in patients with CHF.Chronic pancreatic tissue hypoxic injury driven by prolonged splanchnic hypoperfusion is likely to contribute to malnutrition and cachexia in patients with CHF.On the other hand,CP and PEI seem to be an independent risk factor associated with an increased risk of cardiovascular events.

Upfront surgery of small intestinal neuroendocrine tumors. Time to reconsider?

Small intestinal neuroendocrine tumors(SI-NETs) may demonstrate a widely variable clinical behavior but usually it is indolent. In cases with localized disease, locoregional resective surgery(LRS) is generally indicated with a curative intent. LRS of SI-NETs is also the recommended treatment when symptoms are present, regardless of the disease stage. Concerning asymptomatic patients with distant metastases, prophylactic LRS has been traditionally suggested to avoid possible future complications. Even the current European Neuroendocrine Tumor Society guidelines emphasize a possible effect of LRS in Stage IV SINETs with unresectable liver metastases. On the contrary, the 2017 National Comprehensive Cancer Network Guidelines on carcinoid tumors do not support the resection of a small, asymptomatic, relatively stable primary tumor in the presence of unresectable metastatic disease. Furthermore, a recent study revealed no survival advantage for asymptomatic patients with distant-stage disease who underwent upfront LRS. At the aforementioned paper, it was suggested that delayed surgery as needed was comparable with the upfront surgical approach in terms of postoperative morbidity and mortality, the length of the hospital stay and the rate of incisional hernia repairs but was associated with fewer reoperations for bowel obstruction. On the other hand, it is also important to note that some patients might benefit from a prophylactic surgical approach and our attention should focus on identifying this patient population.

Genomic and pharmacogenetic studies of childhood acute lymphoblastic leukemia

With the cure rate of childhood acute lymphoblastic leukemia （ALL） approaching 90%, further improvement in the treatment outcome and quality of life of patients will require better understanding of the mechanisms of drug resistance, identifying new leukemic cell genetic lesions that are amendable to available target therapy, and optimizing treatment based on host pharmacodynamics and pharmacogenomics. Deeper characterization of leukemic cell genetic abnormalities has discovered new subtypes of leukemia such as early T-cell precursor ALL and Philadelphia chromosome-like ALL, and identified many genomic alterations that have diagnostic, prognostic, or therapeutic implications. In this regard, several novel fusion transcripts are responsive to ABL tyrosine kinase inhibitors and potentially to JAK inhibitors. Genome-wide analyses have also unraveled the role of inherited cancer predisposing genes and small nucleotide polymorphisms of several genes in the development of childhood ALL. These advances promise to lead to more sophisticated personalized treatment strategies in the near future.

Adherence to medication: A nation-wide study from the Children's Cancer Hospital, Egypt

AIM: To investigate adherence to medical regimen and predictors for non-adherence among children with cancer in Egypt. METHODS: We administered two study specific questionnaires to 304 parents of children diagnosed with cancer at the Children's Cancer Hospital in Cairo, Egypt, one before the first chemotherapy treatment and the other before the third. The questionnaires were translated to colloquial Egyptian Arabic, and due, to the high illiteracy level in Egypt an interviewer read thequestions in Arabic to each parent and registered the answers. Both questionnaires consisted of almost 90 questions each. In addition, a Case Report Form was filled in from the child's medical journal. The study period consisted of 7 mo(February until September 2008) and we had a participation rate of 97%. Descriptive statistics are presented and Fisher's exact test was used to check for possible differences between the adherent and non-adherent groups. A P-value below 0.05 was considered significant. Software used was SAS version 9.3 for Windows(SAS Institute Inc., Cary, NC, United States).RESULTS: Two hundred and eighty-one(90%) parents answered the second questionnaire, regarding their child's adherence behaviour. Approximately two thirds of the children admitted to their third chemotherapy treatment had received medical recommendations upon discharge from the first or second chemotherapy treatment(181/281, 64%). Sixty-eight percent(123/181) of the parents who were given medical recommendations reported that their child did not follow the recommendations. Two main predictors were found for non-adherence: child resistance(111/123, 90%) and inadequate information(100/123, 81%). In the adherent group, 20% of the parents(n = 12/58) reported trust in their child's doctor while 14 percent 8/58 reported trust in the other health-care professionals. Corresponding numbers for the non-adherent group are 8/123(7%) for both their child's doctor and other health-care professionals. Almost all of the parents expressed a lack of optimism towards the treatment(116/121, 96%), yet they reported an intention to continue with the treatment for two main reasons, for the sake of their child's life(70%)(P = 0.005) and worry that their child would die if they discontinued the treatment(81%)(P < 0.0001).CONCLUSION: Non-adherence to medical regimen is common among children diagnosed with cancer inEgypt, the main reasons being child resistance and inadequate information.

Genome of the Giant Panda Roundworm Illuminates Its Host Shift and Parasitic Adaptation

Baylisascaris schroederi,a roundworm(ascaridoid)parasite specific to the bamboofeeding giant panda(Ailuropoda melanoleuca),represents a leading cause of mortality in wild giant panda populations.Here,we present a 293-megabase chromosome-level genome assembly of B.schroederi to infer its biology,including host adaptations.Comparative genomics revealed an evolutionary trajectory accompanied by host-shift events in ascaridoid parasite lineages after host separations,suggesting their potential for transmission and rapid adaptation to new hosts.Genomic and anatomical lines of evidence,including expansion and positive selection of genes related to the cuticle and basal metabolisms,indicate that B.schroederi undergoes specific adaptations to survive in the sharp-edged bamboo-enriched gut of giant pandas by structurally increasing its cuticle thickness and efficiently utilizing host nutrients through gut parasitism.Additionally,we characterized the secretome of B.schroederi and predicted potential drug and vaccine targets for new control strategies.Overall,this genome resource provides new insights into the host adaptation of B.schroederi to the giant panda as well as the host-shift events in ascaridoid parasite lineages.Our findings on the unique biology of B.schroederi will also aid in the development of prevention and treatment measures to protect giant panda populations from roundworm parasitism.

LIBRA:an adaptative integrative tool for paired single-cell multi-omics data

Background:Single-cell multi-omics technologies allow a profound system-level biology understanding of cells and tissues.However,an integrative and possibly systems-based analysis capturing the different modalities is challenging.In response,bioinformatics and machine learning methodologies are being developed for multi-omics single-cell analysis.It is unclear whether current tools can address the dual aspect of modality integration and prediction across modalities without requiring extensive parameter fine-tuning.Methods:We designed LIBRA,a neural network based framework,to learn translation between paired multi-omics profiles so that a shared latent space is constructed.Additionally,we implemented a variation,aLIBRA,that allows automatic fine-tuning by identifying parameter combinations that optimize both the integrative and predictive tasks.All model parameters and evaluation metrics are made available to users with minimal user iteration.Furthermore,aLIBRA allows experienced users to implement custom configurations.The LIBRA toolbox is freely available as R and Python libraries at GitHub(TranslationalBioinformaticsUnit/LIBRA).Results:LIBRA was evaluated in eight multi-omic single-cell data-sets,including three combinations of omics.We observed that LIBRA is a state-of-the-art tool when evaluating the ability to increase cell-type(clustering)resolution in the integrated latent space.Furthermore,when assessing the predictive power across data modalities,such as predictive chromatin accessibility from gene expression,LIBRA outperforms existing tools.As expected,adaptive parameter optimization(aLIBRA)significantly boosted the performance of learning predictive models from paired data-sets.Conclusion:LIBRA is a versatile tool that performs competitively in both“integration”and“prediction”tasks based on single-cell multi-omics data.LIBRA is a data-driven robust platform that includes an adaptive learning scheme.

Precision medicine in acute lymphoblastic leukemia

The cure rate of childhood acute lymphoblastic leukemia(ALL)has exceeded 90%in some contemporary clinical trials.However,the dose intensity of conventional chemotherapy has been pushed to its limit.Further improvement in outcome will need to rely more heavily on molecular therapeutic as well as immuno-and cellular-therapy approaches together with precise risk stratification.Children with ETV6-RUNX1 or hyperdiploid>50 ALL who achieve negative minimal residual disease during early remission induction are suitable candidates for reduction in treatment.Patients with Philadelphia chromosome(Ph)-positive or Ph-like ALL with ABL-class fusion should be treated with dasatinib.BH3 profiling and other preclinical methods have identified several high-risk subtypes,such as hypodiplod,early T-cell precursor,immature T-cell,KMT2A-rearranged,Ph-positive and TCF-HLF-positive ALL,that may respond to BCL-2 inhibitor venetoclax.There are other fusions or mutations that may serve as putative targets,but effective targeted therapy has yet to be established.For other high-risk patients or poor early treatment responders who do not have targetable genetic lesions,current approaches that offer hope include blinatumomab,inotuzumab and CAR-T cell therapy for B-ALL,and daratumumab and nelarabine for T-ALL.With the expanding therapeutic armamentarium,we should start focus on rational combinations of targeted therapy with non-overlapping toxicities.