Aims: This study aims to evaluate the drug-drug interaction（DDI） between hetrombopag and cyclosporine in healthy Chinese subjects. Methods: Twenty-six eligible subjects enrolled in this single-center, single-sequence, open-label, DDI study with three treatment periods, receiving 5 mg hetrombopag once on day 1, 100 mg cyclosporine twice daily from day 11 to day 15, and 5 mg hetrombopag + 100 mg cyclosporine on day 16. Serial blood samples were collected for pharmacokinetic evaluation. Adverse events were monitored throughout the study. Results: The plasma hetrombopag geometric mean ratios (GMRs) (90% CI) of Cmax, AUC0-t and AUC0-∞ of co-administration of hetrombopag with cyclosporine vs hetrombopag alone are 95.97% (70.08%, 131.43%), 105.75% (75.04%, 149.04%) and 104.19% (74.71%, 145.32%), respectively, indicating multiple doses of cyclosporine had minimal effects on hetrombopag exposure. The GMRs (90% CI) of Cmax and AUCss,tau for blood cyclosporine of co-administration vs cyclosporine alone were 100.49% (91.89%, 109.89%) and 100.81% (107.88%, 103.82%), respectively, suggesting a single dose of hetormbopag had no impact on the exposure of cyclosporine. Co-administration of hetormbopag with cyclosporine was generally well tolerated. Conclusion: No clinically significant DDI was observed when co-administration of hetrombopag with cyclosporine. No additional dose adjustment is warranted for this combination.
1. Animal abundance estimation is increasingly based on drone or aerial survey photography. Manual post-processing has been used extensively, however volumes of such data are increasing, necessitating some level of automation, either for complete counting, or as a labour-saving tool. Any automated processing can be challenging when using the tools on species that nest in close formation such as Pygoscelid penguins. 2. We present here an adaptation of state-of-the-art crowd-counting methodologies for counting of penguins from aerial photography. 3. The crowd-counting model performed significantly better in terms of model performance and computational efficiency than standard Faster RCNN deep-learning approaches and gave an error rate of only 0.8 percent. 4. Crowd-counting techniques as demonstrated here have the ability to vastly improve our ability to count animals in tight aggregations, which will demonstrably improve monitoring efforts from aerial imagery.
We report a case of hemophagocytic lymphohistiocytosis associated with acute myeloid leukemia. The usual etiologies of hemophagocytic lymphohistiocytosis were absent. Hemophagocytic lymphohistiocytosis secondary to acute myeloid leukemia is rare and deserves the attention of clinicians. Hemophagocytic lymphohistiocytosis may be masked by the tumour process, often making the diagnosis difficult.
Drought and flooding occur at opposite ends of the soil moisture spectrum yet resulting stress responses that occur in plants share many similarities. Drought limits root water uptake to which plants respond with stomatal closure and reduced leaf gas exchange. Flooding limits root metabolism due to soil anoxia, which also limits root water uptake and leaf gas exchange. As drought and flooding can occur consecutively in the same system and resulting plant stress responses share similar mechanisms, a single theoretical framework that integrates plant responses over a continuum of soil water conditions from drought to flooding is attractive. Based on a review of recent literature, we integrated the main plant eco-physiological mechanisms in a single theoretical model with a focus on plant water transport, plant oxygen dynamics, and leaf gas exchange. We used the Soil-Plant-Atmosphere-Continuum model as “backbone” for our theoretical framework development, and subsequently incorporated interactions between processes that regulate plant water and oxygen status, levels of abscisic acid and ethylene hormones and resulting acclimation strategies in response to drought, waterlogging, and complete submergence. Our theoretical framework provides a basis for the development of mathematical models to describe plant responses to the soil moisture continuum from drought to flooding.
Geopolymer concrete shares similar mechanical properties with ordinary Portland cement (OPC) concrete, and is even provided with better performances in high temperature and high corrosion circumstances. However, geopolymer binder is still subject to the disadvantages of large shrinkage and high brittleness, which greatly limit its application. Fiber reinforcement is widely used in various geopolymer systems to overcome the brittleness issue, but retains the high strength. Over the past 10 years, a significant advance has been made in the research of fiber reinforced geopolymers in terms of toughening efficiency and durability improvement. This paper, as a mini review, focuses on three types of fibers, i.e., inorganic fiber, natural fiber and synthetic fiber, in geopolymers, and their specific effects on compressive, flexural and tensile strengths, fractural toughness, shear strength and durability including shrinkage, chemical and freezing-thaw resistances. The recement understanding of bonding mechanism and fiber-geopolymer interface are also discussed, and knowledge gaps and future work challenges are correspondingly pointed out.
The iterative weighted shrinkage-thresholding algorithm (IWSTA) has shown superiority to the classic unweighted iterative shrinkage-thresholding algorithm (ISTA) for solving linear inverse problems, which address the attributes differently. This paper proposes a new entropy regularized IWSTA (ERIWSTA) that adds an entropy regularizer to the cost function to measure the uncertainty of the weights to stimulate attributes to participate in problem solving. Then, the weights are solved with a Lagrange multiplier method to obtain a simple iterative update. The weights can be explained as the probability of the contribution of an attribute to the problem solution. Experimental results on CT image restoration show that the proposed method has better performance in terms of convergence speed and restoration accuracy than the existing methods.
Understanding the drivers of morphological convergence requires investigation into its relationship with behavior and niche-space, and such investigations in turn provide insights into evolutionary dynamics, functional morphology, and life history. Mygalomorph spiders (trapdoor spiders and their kin) have long been associated with high levels of homoplasy, and many convergent features can be intuitively associated with different behavioral niches. Using genus-level phylogenies based on recent genomic studies and a newly assembled matrix of discrete behavioral and somatic morphological characters, we reconstruct the evolution of burrowing behavior in the Mygalomorphae, compare the influence of behavior and evolutionary history on somatic morphology, and test hypotheses of correlated evolution between specific morphological features and behavior. Our results reveal the simplicity of the mygalomorph adaptive landscape, with opportunistic, web-building taxa at one end, and burrowing/nesting taxa with structurally-modified burrow entrances (e.g., a trapdoor) at the other. Shifts in behavioral niche, in both directions, are common across the evolutionary history of the Mygalomorphae, and several major clades include taxa inhabiting both behavioral extremes. Somatic morphology is heavily influenced by behavior, with taxa inhabiting the same behavioral niche often more similar morphologically than more closely-related but behaviorally-divergent taxa, and we were able to identify a suite of 11 somatic features that show significant correlation with particular behaviors. We discuss these findings in light of the function of particular morphological features, niche dynamics within the Mygalomorphae, and constraints on the mygalomorph adaptive landscape relative to other spiders.
A 68-year-old African American male who presented to the emergency department with back and abdominal pain. Imaging showed a posterior mediastinal mass interposed between the carina, the left mainstem bronchus, and the descending thoracic aorta. Biopsy of the mass favored a metastatic prostate carcinoma, which is an extremely rare presentation.
Introduction. The concept of ventricular anatomy as a single muscular band was initially described by Francisco Torrent-Guasp in 1972 1 and since then, there have been multiple novel contributions to the understanding of the morphology and function of the heart. To date, this concept has been supported and denied by multiple groups of professionals reflecting both the enthusiasm and resistance to the new concept of the single muscle band model. Currently, the single muscular band is the model that meets all the requirements to explain the performance of cardiac mechanics, and its distinctive feature to determine the characteristics of the structure.
Hematological toxicity (hematotoxicity) is the most common long-term adverse effect following the use of CD19-chimeric antigen receptor (CD19-CAR) T-cell therapies. However, its management remains unclear. We present the case of a 21-year-old who received CD19-CAR T-cell therapy for relapse following a haploidentical transplant. He developed hematotoxicity and consequently multiple life-threatening infections. We administered a CD34+ hematopoietic stem cell boost (HSCB) from his transplant donor that led to hematopoietic recovery and resolution of his infections without any effect on the activity of CD19-CAR T cells. CD34+ HSCB can be a safe and effective option to treat hematotoxicity following CD19-CAR T-cell therapy.
Objective: Patent ductus arteriosus (PDA) is a common complication among premature infants, and it may be responsible for prematurity-related complications, such as bronchopulmonary dysplasia (BPD). It is unclear whether different interventional methods contribute to the severity of BPD. To date, surgical ligation and the transcatheter approach have shown equal success in premature infants with hemodynamically significant PDA after medical treatment failure. Immediate improvement in the respiratory condition after transcatheter closure has been reported. However, the short-term pulmonary outcome has not been clarified yet. Methods: This retrospective study investigated infants born with a body weight less than 1000 g and underwent either surgical ligation or transcatheter closure of PDA in a single tertiary institution. The infants were divided into groups according to the type of procedure (surgical ligation or transcatheter occlusion). The primary outcome was the severity of BPD at discharge or at post-menstrual age of 36 weeks. The outcome was analyzed with logistic regression. Results: Forty-four patients met the inclusion criteria, and of these, 14 underwent transcatheter occlusion and 30 underwent surgical ligation. The overall birth body weight and gestational age ranges were not different. The univariate model revealed an association between the procedure type and BPD severity. The multivariate model confirmed associations of BPD severity with procedure type and severe respiratory distress syndrome requiring surfactant after adjusting for confounders. Conclusion: Compared with the transcatheter approach, surgery for PDA in extremely preterm infants is associated with severe BPD at discharge. Further large-scale studies are needed to determine the exact mechanism.
Here we present a case of metastatic PNET which arose from an immature teratoma that was refractory to standard Ewing sarcoma chemotherapy. This PNET was determined to have elevated levels of ALK protein via IHC. The patient was treated with crizotinib on a palliative basis with a sustained response.
An 83-year-old-male presented with obstructive jaundice, whose imaging was consistent with the cholangiocarcinoma of the distal common bile duct. The tumor markers were within normal limits. IgG4 level was raised, therefore, IgG4-sclerosing cholangitis was made as the provisional diagnosis. Steroid therapy was started to which he responded well.
Study Objective: To explore the effectiveness of a modified suspension method combined with Gasless single-port laparoscopy (MS-GSPL) for the treatment of benign ovarian tumors. The aim of this approach is to provide a convenient, economical,and minimally invasive method that is suitable for widespread use, even in middle- and low-income countries or primary hospitals. Design: A retrospective comparative study. Setting: University teaching hospital. Patients: Thirty-six cases were treated with MS-GSPL, and thirty-six cases were treated with single-port laparoscopy (SPL). Interventions: Use a modified suspension method combined with Gasless single-port laparoscopy for the treatment of benign ovarian tumors. Measurements and Main Results: There are no significant differences in age, body mass index,previous pelvic surgery, tumor diameter ,and tumor pathologic outcomes between MS-GSPL group and SPL group.The median operation times were 50(Q1~Q3 , 44~62.25)min in the MS-GSPL group and 60.5(Q1~Q3 , 57.25~78)min in the SPL group with a significant difference. The median estimated blood loss were 40 (Q1~Q3 , 30~50)ml in the MS-GSPL group and 50(Q1~Q3 , 30~60) ml in the SPL group with no significant difference. Compared with SPL group, patients in MS-GSPL group had earlier postoperative exhaust times, shorter hospital stays and lower costs, and all these differences were statistically significant(P<0.05). There was a strong positive correlation between operation time and BMI in the MS-GSPL groups. Conclusion: The patients receiving MS-GSPL treatment have quick postoperative recoveries. MS-GSPL is a novel, safe and economical surgical method that is suitable for extensive clinical development in middle- and low-income countries or primary hospitals.
Objective: To investigate whether the Antenatal Late Preterm Steroids (ALPS) trial, has been translated into clinical practice in Canada and the United States. Temporal trends in optimal and suboptimal antenatal corticosteroid (ACS) use among late preterm deliveries were also assessed. Design: A retrospective cohort study. Setting: USA and Canada, 2007 to 2020. Population: All live births in the US (n= 32,476,039) and Nova Scotia, Canada (n= 116,575). Methods and Main outcome measured: Using data from the Natality database and the Nova Scotia Atlee Perinatal Database, ACS administration within specific categories of gestational age was assessed by calculating rates per 100 live births. Temporal trends in optimal, and suboptimal ACS use were also assessed. Results: In Nova Scotia, the rate of any ACS administration increased significantly among women delivering at 35-36 weeks, from 15.2% in 2007-2016 to 19.6% in 2017-2020 (OR 1.36, 95%CI 1.14, 1.62). In the U.S., among live births at 35-36 weeks’ gestation, any ACS use increased from 4.1% in 2007–2016 to 18.5% in 2017–2020 (OR 5.33, 95% CI 5.28–5.38). Among infants between 24 and 34 weeks’ gestation in Nova Scotia, 32% received optimally timed ACS, while 47% received ACS with suboptimal timing. Of the women who received ACS in 2020, 34% in Canada and 20% in the United States delivered at ≥37 weeks. Conclusion: Publication of the ALPS trial resulted in increased ACS administration at late preterm gestation in Nova Scotia, Canada and the U.S.. However, a significant fraction of women receiving ACS prophylaxis delivered at term gestation.
Aim: Cisplatin causes acute kidney injury (AKI) in approximately one-third of patients. Serum creatinine and urinary output are poor markers of cisplatin-induced (AKI). Metabolomics was utilized to identify predictive or early diagnostic biomarkers of cisplatin-induced AKI. Methods: Thirty-one adult head and neck cancer patients receiving cisplatin (dose ≥ 70 mg m2 -1) were recruited for metabolomics analysis. Urine and serum samples were collected prior to cisplatin (pre), 24-48 hours after cisplatin (24-48h), and 5-14 days (post) after cisplatin. Based on serum creatinine concentrations measured at the post timepoint, 11/31 patients were classified with clinical AKI. Untargeted metabolomics was performed using liquid chromatography-mass spectrometry. Results: Metabolic discrimination was observed between “AKI” patients and “no AKI” patients at all timepoints. Urinary glycine, hippuric acid sulfate, 3-hydroxydecanedioc acid, and suberate were significantly different between AKI patients and no AKI patients prior to cisplatin infusion. Urinary glycine and hippuric acid sulfate were lower (-2.22-fold and -8.85-fold), whereas 3-hydroxydecanedioc acid and suberate were higher (3.62-fold and 1.91-fold) in AKI patients relative to no AKI patients. Several urine and serum metabolites were found to be altered 24-48 hours following cisplatin infusion, particularly metabolites involved with mitochondrial energetics. Conclusion: We propose glycine, hippuric acid sulfate, 3-hydroxydecanedioc acid, and suberate as predictive biomarkers of predisposition to cisplatin-induced AKI. Metabolites indicative of mitochondrial dysfunction may serve as early markers of subclinical AKI.
C 4 crops such as Zea mays (maize) and Sorghum bicolor (sorghum) are important in both food and bioenergy systems. In these crops, carbon assimilation is limited at high heat by the thermolabile protein rubisco activase (RCA). We present a comparative study of assimilation and RCA function in the C 4 grasses maize, sorghum, and the C 4 model grass Setaria viridis (setaria) during a 48 hour heat stress acclimation. Western blots and biochemical assays show that each species uses a different strategy to acclimate to heat. All grasses shift the predominant ꞵ proteoform of RCA from a 41kD to a 43kD form. In addition, sorghum expresses the ⍺ isoform, while all three grasses transiently increase expression of the ꞵ isoform. The response of RCA to magnesium ions and to ADP is also altered. After heat treatment, maize RCA is more sensitive to inhibition by magnesium but loses sensitivity to ADP. Different cultivars of maize show differences in assimilation and protein expression. Because each grass expressed and regulated RCA differently, we recommend that future study of RCA should examine each grass individually rather than relying on a model organism.