Search

Cultured human skeletal-muscle satellite cells have properties of mesenchymal stem cells (skeletal muscle satellite cell-derived mesenchymal stem cells, SkMSCs) and play anti-inflammatory roles by secreting prostaglandin E2 and hepatocyte growth factor (HGF). To evaluate the utility of SkMSCs in treating liver diseases, we determined whether SkMSCs could ameliorate acute liver and gut inflammation induced by binge ethanol administration. Binge drinking of ethanol led to weight loss in the body and spleen, liver inflammation and steatosis, and increased serum ALT and AST levels (markers of liver injury), along with increased IL-1β, TNF-α, and iNOS expression levels in mice. However, levels of these binge-drinking-induced indicators were reduced by a single intraperitoneal treatment of SkMSCs. Furthermore, levels of bacteria-derived lipopolysaccharide decreased in the livers and sera of ethanol-exposed mice after SkMSC administration. SkMSCs decreased the extent of tissue inflammation and reduced villus and crypt lengths in the small intestine after alcohol binge drinking. SkMSCs also reduced the leakage of blood albumin, an indicator of leaky gut, in the stool of ethanol-exposed mice. Alcohol-induced damage to human colonic Caco-2/tc7 cells was also alleviated by HGF. Therefore, a single treatment with SkMSCs can attenuate alcoholic liver damage by reducing inflammatory responses in the liver and gut, suggesting that SkMSCs could be used in cell therapy to treat alcoholic liver diseases., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: There is limited epidemiologic data on pediatric basketball injuries and the comparison of these injuries before and after adolescence and between male and female athletes., Purpose: To assess common sex- and age-based injury patterns in pediatric basketball players., Study Design: Descriptive epidemiology study., Methods: Injury data from the National Electronic Injury Surveillance System (NEISS) and participation data from the National Sporting Goods Association were used to complete this study. Data on pediatric basketball injuries between January 2012 and December 2018 in patients aged 7 to 11 years (childhood) and 12 to 17 years (adolescence) were extracted and used to calculate national injury incidence rates with 95% CIs. Sex and age group patterns were examined utilizing Pearson chi-square tests. Z tests were conducted for the comparison of injury rates between female and male athletes in each age group and overall injury rate across age groups., Results: An average of 9582 basketball injuries were reported annually in the NEISS, which calculated to an annual national estimate of 294,920 injuries. The most common diagnoses were ankle strain/sprain (17.7%), finger strain/sprain/fracture (12.1%), concussion/head injury (9.4%), knee strain/sprain (4.5%), and facial laceration (3.3%). There was a significant increase in injury prevalence in adolescents (12- to 17-year-old category: 238,678 injuries per year) when compared with childhood (7- to 11-year-old category: 56,242 injuries per year) ( P < .0001). Concussions/head injuries occurred at a high rate in childhood, second only to finger strain/sprain/fracture, and at a similar rate in females and males (injuries per 100,000 athlete-days: 4.9 [95% CI, 3.1-6.7] vs. 5.9 [4.3-7.5], respectively; P = .41). From childhood to adolescence, injury prevalence increased for all areas and across both sexes, except for female finger strain/sprain/fracture; however, the rate of increase for concussion/head injuries and knee injuries was significantly higher in female compared with male athletes ( P < .0001 for both). In adolescents, ankle injuries were the most common injury overall., Conclusion: Ankle injuries continue to be the most predominant pediatric basketball injury. However, disproportionate rates of both knee and concussion/head injuries in female athletes during adolescent basketball are of concern and have implications for injury prevention., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: P.L.W. has received education payments from Pylant Medical and royalties from Elsevier. H.B.E. has received education payments from Pylant Medical, nonconsulting fees from Smith & Nephew, speaking fees from Synthes, royalties from Elsevier, and hospitality payments from Arthrex. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2022.)

Anterior gradient protein 2 homolog (AGR2), an endoplasmic reticulum protein, is secreted in the tumor microenvironment. AGR2 is a member of the disulfide isomerase family, is highly expressed in multiple cancers, and promotes cancer metastasis. In this study, we found that etravirine, which is a non-nucleoside reverse transcriptase inhibitor, could induce AGR2 degradation via autophagy. Moreover, etravirine diminished proliferation, migration, and invasion in vitro. Moreover, in an orthotopic xenograft mouse model, the combination of etravirine and paclitaxel significantly suppressed cancer progression and metastasis. This drug may be a promising therapeutic agent for the treatment of ovarian cancer.

Cadmium (Cd) can adversely affect aquatic life, altering reproductive and molting processes in crustaceans. The objective of this study was to evaluate the influence of Cd on reproduction and molting in the crab Callinectes danae. Adult females were obtained from environments with different levels of pollution: low (LC), medium (MC), and high contaminated (HC) areas. Animals from LC, MC, and HC areas were exposed to 0, 0.5, and 2 mg L -1 of CdCl 2 for 3 h. Cd bioaccumulation, oxidative stress (evaluated by antioxidant enzymes activity), and lipid peroxidation (LPX) were analyzed in mature ovaries (stage II), gills, and hepatopancreas. The expression levels of crustacean hyperglycemic hormone (CHH) and molt-inhibiting hormone (MIH) genes were quantified in the eyestalks, while 17β-estradiol (E2) and melatonin concentration were measured in the hemolymph. Cd bioaccumulated mainly in the hepatopancreas and gills, with increased E2, LPX, and antioxidant enzymes in HC compared to the LC region. Decreased CHH and MIH transcripts were observed in the animals from HC regions compared to LC and MC areas. Physiological differences were recorded, especially for bioaccumulation, oxidative stress, and hormone levels, in animals sampled in HC areas compared to LC and MC regions. In conclusion, the physiological damage triggered by Cd could be reduced due to higher levels of melatonin and antioxidant enzymes in HC areas., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: There are unmet needs associated with the current treatment strategies for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) due to the poor treatment outcomes of these strategies. Roflumilast, a selective phosphodiesterase-4 inhibitor used for treating chronic obstructive pulmonary disease, is effective against B-cell malignancy via phosphoinositide 3-kinase (PI3K)-activity suppression. We analyzed the effects of roflumilast combined with ESHAP (etoposide, cisplatin, methylprednisolone, and cytarabine) chemotherapy in experimental and clinical settings., Materials and Methods: An in vitro study using lymphoma cell lines and a pilot study on relapsed/refractory DLBCL patients were conducted to investigate the effects and mechanism of the combination of roflumilast and chemotherapy. The complete response (CR), overall response rate (ORR), and 1-year progression-free survival (PFS) were analyzed., Results: We found that roflumilast is efficient when combined with other chemotherapy drugs, especially cytarabine. Synergistic effects between these two drugs influence the translation of mammalian target of rapamycin and myeloid cell leukemia 1, resulting in apoptosis and inhibition of B-cell lymphoma proliferation. In clinical setting, the roflumilast group showed better rates of CR (46.2% vs. 34.6%), ORR (76.9% vs. 53.8%), and 1-year PFS (50.0% vs. 25.9%) compared with the control group, though not statistically significant. The roflumilast group showed a higher incidence of asthenia and gastrointestinal adverse events. However, grade 3 or 4 adverse events were similar in both groups., Conclusion: We found that roflumilast, when combined with ESHAP chemotherapy, for relapsed/refractory DLBCL was clinically active and well tolerated. This combined treatment was able to suppress PI3K activity, which is correlated with the degree of clinical response.

This study evaluated the structural stability of subway structures based on adjacent excavations by comparing automatically measured and numerically analyzed data. The reliability of the automated measurement methodology was evaluated by first applying probability statistical analysis to the measured results and then comparing these results with the numerically analyzed results. An improvement in the calculation method evaluation system, including the method of processing and analysis of the automatically measured data of subway structures through the average value of probability density, was proposed. As a result of the field measurement and numerical analysis, the measured results of tunnel displacement and track deformation exhibited some differences. However, it was determined that the construction stage and location where the maximum values of the tunnel displacement and track deformation occurred had similarities.

Background: We tested the hypothesis that transplant centers (TCs) with higher volumes have higher donor heart (DH) offer utilization rates., Methods: Using the Annual Data reports of the US Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients (SRTR) we reviewed all adult heart transplant offers between July 1, 2016 and June 29, 2019. Unadjusted donor offer utilization rates and observed to expected (O/E) DH utilization ratios adjusted using the SRTR model were calculated for each TC for all DH offers and for the following sub-categories: DH with left ventricular ejection fraction <60%, DH >40 years, DH >500 miles from TC, "hard-to-place hearts" (defined as those offered to >50 TCs) and DH designated as increased infectious risk. Univariable linear regression was used to identify a relationship between average yearly center volume and DH utilization., Results: During the study 118,841 total offers were made to 107 TCs and 8300 transplants were performed. The unadjusted utilization rate was not associated with TC volume for all donor offers (p = .517). However, among all subcategories other than DH >40 years, the unadjusted DH utilization rate was associated with TC volume (p < .05). In addition, using the adjusted SRTR O/E ratio, there was a significant impact of TC volume on utilization rate for all donor offers (for an increase TC volume of 10 transplants/year coefficient = 0.095, 95% confidence interval: 0.037-0.151, p = .001). This relationship persisted with an identifiable change for each of the subcategories (p ≤ .001)., Conclusions: TC volume is significantly correlated to DH offer utilization rate., (© 2021 Wiley Periodicals LLC.)

Traumatic brain injury (TBI) is often experienced under stressful circumstances that can lead to symptoms of post-traumatic stress disorder (PTSD) and neurobehavioral symptoms of brain injury. There is considerable symptom overlap in the behavioral expression of these conditions. Psychometric network analysis is a useful approach to investigate the role of specific symptoms in connecting these two disorders and is well suited to explore their interrelatedness. This study applied network analysis to examine the associations among PTSD and TBI symptoms in a sample of Service Members and Veterans (SM/Vs) with a history of TBI one year after injury. Responses to the Neurobehavioral Symptom Inventory (NSI) and PTSD Checklist-Civilian version (PCL-C) were obtained from participants who completed comprehensive inpatient rehabilitation services across five Veterans Affairs polytrauma rehabilitation centers. Participants (N = 612) were 93.1% male with an average age of 36.98 years at injury. The analysis produced a stable network. Within the NSI symptom groups, the frustration symptom was an important bridge between the affective and cognitive TBI symptoms. The PCL-C nodes formed their own small cluster with hyperarousal yielding connections with the affective, cognitive, and somatic symptom groups. Consistent with this observation, the hyperarousal node had the second strongest bridge centrality in the network. Hyperarousal appears to play a key role in holding together this network of distress and thus represents a prime target for intervention among individuals with elevated symptoms of PTSD and a history of TBI. Network analysis offers an empirical approach to visualizing and quantifying the associations among symptoms. The identification of symptoms that are central to connecting multiple conditions can inform diagnostic precision and treatment selection.

Women and men share similar diseases; however, women have unique issues, including gynecologic diseases and diseases related to menstruation, menopause, and post menopause. In recent decades, scientists paid more attention to natural products and their derivatives because of their good tolerability and effectiveness in disease prevention and treatment. Olive oil is an essential component in the Mediterranean diet, a diet well known for its protective impact on human well-being. Investigation of the active components in olive oil, such as oleuropein and hydroxytyrosol, showed positive effects in various diseases. Their effects have been clarified in many suggested mechanisms and have shown promising results in animal and human studies, especially in breast cancer, ovarian cancer, postmenopausal osteoporosis, and other disorders. This review summarizes the current evidence of the role of olives and olive polyphenols in women's health issues and their potential implications in the treatment and prevention of health problems in women.

Soil salinity severely hampers agricultural productivity. Under salt stress, excess Na + accumulation causes cellular damage and plant growth retardation, and membrane Na + transporters play central roles in Na + uptake and exclusion to mitigate these adverse effects. In this study, we performed sos1 suppressor mutant (named sup) screening to uncover potential genetic interactors of SOS1 and additional salt tolerance mechanisms. Map-based cloning and sequencing identified a group of mutants harboring dominant gain-of-function mutations in the vacuolar Na + /H + antiporter gene AtNHX1. The gain-of-function variants of AtNHX1 showed enhanced transporter activities in yeast cells and increased salt tolerance in Arabidopsis wild type plants. Ion content measurements indicated that at the cellular level, these gain-of-function mutations resulted in increased cellular Na + accumulation likely due to enhanced vacuolar Na + sequestration. However, the gain-of-function suppressor mutants showed reduced shoot Na + but increased root Na + accumulation under salt stress, indicating a role of AtNHX1 in limiting Na + translocation from root to shoot. We also identified another group of sos1 suppressors with loss-of-function mutations in the Na + transporter gene AtHKT1. Loss-of-function mutations in AtHKT1 and gain-of-function mutations in AtNHX1 additively suppressed sos1 salt sensitivity, which indicates that the three transporters, SOS1, AtNHX1 and AtHKT1 function independently but coordinately in controlling Na + homeostasis and salt tolerance in Arabidopsis. Our findings provide valuable information about the target amino acids in NHX1 for gene editing to improve salt tolerance in crops., (© 2021. The Author(s).)

High quantum yield 3-aminophenylboronic acid-functionalized nitrogen-doped carbon dots (GAAP-CDs) were fabricated using a simple hydrothermal route and used as a sensing probe for toxic hypochlorite (ClO - ). The as-synthesized GAAP-CDs showed absorption peaks at 252, 297, and 370 nm and an emission peak at 375 nm with an excitation wavelength of 310 nm. The quantum yield of GAAP-CDs reached 58.28%, with no noticeable fluorescence change observed under high ionic strength conditions and a three-month long-term test. GAAP-CDs-based ClO - sensing was carried out by UV-vis absorbance and fluorescence spectroscopy; the detection limit was as low as 0.77 μM (linear range of 0-100 μM), and 0.50 μM (linear range of 0.1-100 μM), respectively. In addition, the as-synthesized GAAP-CDs showed excellent selectivity towards ClO - ions in the presence of various interfering chemicals. The satisfactory results from the proposed method of ClO - detection in tap water and drinking water samples, suggesting promising application of GAAP-CDs for ClO - detection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ubiquitination, one of the most frequently occurring post-translational modifications, is essential for regulating diverse cellular processes in plants during abiotic stress. The E3 ubiquitin (Ub) ligase Arabidopsis thaliana really interesting new gene (RING) zinc finger 1 (AtRZF1) mutation is known to enhance drought tolerance in A. thaliana seedlings. To further investigate the function of AtRZF1 in osmotic stress, we isolated Ub-associated protein 1 (AtUAP1) which interacts with AtRZF1 using a yeast two-hybrid system. AtUAP1, a Ub-associated motif containing protein, increased the amount of Ub-conjugated AtRZF1. Moreover, AtUAP1 RNA interference lines were more tolerant to osmotic stress than wild type, whereas AtUAP1-overexpressing (OX) transgenic lines showed sensitive responses, including cotyledon greening, water loss, proline accumulation and changes in stress-related genes expression, indicating that AtUAP1 could negatively regulate dehydration-mediated signaling. In addition, AtUAP1-green fluorescent protein fusion protein was observed in the nuclei of root cells of transgenic seedlings. Genetic studies showed that the AtRZF1 mutation could rescue the sensitive phenotype of AtUAP1-OX lines in response to osmotic stress, suggesting that AtRZF1 was epistatic to AtUAP1 in dehydration signaling. Taken together, our findings describe a new component in the AtRZF1 ubiquitination pathway which controls the dehydration response in A. thaliana., (© The Author(s) 2021. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cancer cells are high in heterogeneity and versatility, which can easily adapt to the external stresses via both primary and secondary resistance. Targeting of tumour microenvironment (TME) is a new approach and an ideal therapeutic strategy especially for the multidrug resistant cancer. Recently, we invented AANG, a natural compound formula containing traditional Chinese medicine (TCM) derived Smad3 inhibitor Naringenin (NG) and Smad7 activator Asiatic Acid (AA), for rebalancing TGF-β/Smad signalling in the TME, and its implication on the multidrug resistance is still unexplored. Here, we observed that an equilibrium shift of the Smad signalling in patients with hepatocellular carcinoma (HCC), which was dramatically enhanced in the recurrent cases showing p-glycoprotein overexpression. We optimized the formula ratio and dosage of AANG that effectively inhibit the proliferation of our unique human multidrug resistant subclone R-HepG2. Mechanistically, we found that AANG not only inhibits Smad3 at post-transcriptional level, but also upregulates Smad7 at transcriptional level in a synergistic manner in vitro. More importantly, AANG markedly suppressed the growth and p-glycoprotein expression of R-HepG2 xenografts in vivo. Thus, AANG may represent a novel and safe TCM-derived natural compound formula for overcoming HCC with p-glycoprotein-mediated multidrug resistance., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The blue crab, Callinectes sapidus (Rathbun, 1896) is an economically, culturally, and ecologically important species found across the temperate and tropical North and South American Atlantic coast. A reference genome will enable research for this high-value species. Initial assembly combined 200× coverage Illumina paired-end reads, a 60× 8 kb mate-paired library, and 50× PacBio data using the MaSuRCA assembler resulting in a 985 Mb assembly with a scaffold N50 of 153 kb. Dovetail Chicago and HiC sequencing with the 3d DNA assembler and Juicebox assembly tools were then used for chromosome scaffolding. The 50 largest scaffolds span 810 Mb are 1.5-37 Mb long and have a repeat content of 36%. The 190 Mb unplaced sequence is in 3921 sequences over 10 kb with a repeat content of 68%. The final assembly N50 is 18.9 Mb for scaffolds and 9317 bases for contigs. Of arthropod BUSCO, ∼88% (888/1013) were complete and single copies. Using 309 million RNAseq read pairs from 12 different tissues and developmental stages, 25,249 protein-coding genes were predicted. Between C. sapidus and Portunus trituberculatus genomes, 41 of 50 large scaffolds had high nucleotide identity and protein-coding synteny, but 9 scaffolds in both assemblies were not clear matches. The protein-coding genes included 9423 one-to-one putative orthologs, of which 7165 were syntenic between the two crab species. Overall, the two crab genome assemblies show strong similarities at the nucleotide, protein, and chromosome level and verify the blue crab genome as an excellent reference for this important seafood species., (© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.)

The crustacean molting process is regulated by an interplay of hormones produced by the eyestalk ganglia and Y-organs (YO). Molt-inhibiting hormone and crustacean hyperglycemic hormone released by the sinus gland of the eyestalk ganglia (EG) inhibit the synthesis and secretion of ecdysteroid by the YO, hence regulating hemolymph levels during the molt cycle. The purpose of this study is to investigate the ecdysteroidogenesis pathway, specifically genes linked to changes in ecdysteroid levels occurring at early premolt (ePM). To this end, a reference transcriptome based on YO, EG, and hepatopancreas was de novo assembled. Two genes (cholesterol 7-desaturase Neverland and cytochrome p450 307a1-like Spook) involved in ecdysteroidogenesis were identified from the YO transcriptome using sequence comparisons and transcript abundance. Two other candidates, Hormone receptor 4 and probable cytochrome p450 49a1 potentially involved in ecdysteroidogenesis were also identified. Since cholesterol is the ecdysteroid precursor, a putative cholesterol carrier (Apolipoprotein D-like) was also examined to understand if cholesterol uptake coincided with the increase in the ecdysteroid levels at the ePM stage. The expression level changes of the five candidate genes in the YO were compared between intermolt (IM) and induced ePM (iePM) stages using transcriptomic analysis. Expression analysis using qPCR were carried out at IM, iePM, and normal ePM. The increase in Spook and Neverland expression in the YO at the ePM was accompanied by a concomitant rise in ecdysteroid levels. The data obtained from iePM stage were congruent with those obtained from the normal ePM stage of intact control animals. The present findings support the role of Halloween genes in the ecdysteroidogenesis and molt cycle in the blue crab, Callinectes sapidus., Competing Interests: The authors have declared that no competing interests exist.

Mincle is essential for tumor-associated macrophage (TAM)-driven cancer progression and represents a potential immunotherapeutic target for cancer. Nevertheless, the lack of a specific inhibitor has largely limited its clinical translation. Here, we successfully developed a gene therapeutic strategy for silencing Mincle in a virus-free and tumor-specific manner by combining RNA interference technology with an ultrasound-microbubble-mediated gene transfer system (USMB). We identified a small hairpin RNA (shRNA) sequence shMincle that can silence not only Mincle expression but also the protumoral effector production in mouse bone marrow- and human THP-1-derived macrophages in the cancer setting in vitro . By using our well-established USMB system (USMB-shMincle), the shMincle-expressing plasmids were delivered in a tissue-specific manner into xenografts of human lung carcinoma A549 and melanoma A375 in vivo . Encouragingly, we found that USMB-shMincle effectively inhibited the protumoral phenotypes of TAMs as well as the progression of both A549 and A375 xenografts in a dose-dependent manner in mice without significant side effects. Mechanistically, we identified that USMB-shMincle markedly enhanced the anticancer M1 phenotype of TAMs in the A549 and A375 xenografts by blocking the protumoral Mincle/Syk/nuclear factor κB (NF-κB) signaling axis. Thus, USMB-shMincle may represent a clinically translatable novel and safe gene therapeutic approach for cancer treatment., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Competing Interests: The authors declare that this editorial was written in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

In 2018, the United Network for Organ Sharing (UNOS) adopted a 6-tier system for heart allocation which shifted patterns in listing strategies. The effects of the change on waitlist survival and transplantation rates have yet to be substantiated by analysis of competing outcomes among various listing strategies. This study included all adult patients listed for first-time heart transplantation in UNOS between 10/17/15 and 6/12/20. Clinical characteristics were compared before and after allocation change among various listing strategies: no support, inotropes, intra-aortic balloon pump, durable left ventricular assist device (LVAD), temporary VAD, and extracorporeal membrane oxygenation. Fine-Gray proportional subhazard models were used to estimate the effect of allocation change on competing waitlist outcomes-transplantation, death, or removal from waitlist-among each strategy. During the study period, there were 17 422 patients listed for heart transplantation. Among each listing strategy, clinical characteristics were similar before and after allocation change. Subhazard models demonstrated reduced risk for waitlist mortality (p < .001) among each strategy except temporary VAD and increased transplantation rates (p < .001) among each strategy except for durable LVAD. These results validate the association of the new allocation system on waitlist outcomes across listing strategies., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea., Methods: Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed., Results: A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%)., Conclusion: Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.

Background: We investigated whether distance max , that is, the degree of distance between the upper aerodigestive tract (UAT) mass and the farthest pathologic lymph node, was significantly associated with survival in patients with limited-stage UAT natural killer/T cell lymphoma (NKTCL)., Methods: A total of 157 patients who received chemotherapy (CTx) with/without radiotherapy (RTx) were enrolled., Results: In the survival analysis, an elevated lactate dehydrogenase level [progression-free survival (PFS): hazard ratio (HR), 2.948; 95% confidence interval (CI), 1.606‒5.404; P <0.001; overall survival (OS): HR, 2.619; 95% CI, 1.594‒4.822; P =0.003], short distance max (PFS: HR, 0.170; 95% CI, 0.071‒0.410; P <0.001; OS: HR, 0.142; 95% CI, 0.050‒0.402; P < 0.001), and CTx combined with RTx (HR, 0.168; 95%CI, 0.079‒0.380; P <0.001; OS: HR, 0.193; 95% CI, 0.087‒0.429; P <0.001) had an independent predictive value for PFS and OS., Conclusion: The evaluation of the degree of lymphatic spread and local control by CTx combined with RTx is essential in patients with limited-stage UAT NKTCL.

Objective: Describe rehabilitation needs and factors associated with unmet needs at 5 years post-traumatic brain injury (TBI)., Setting: Five Veterans Affairs (VA) polytrauma rehabilitation centers (PRCs)., Participants: VA TBI Model Systems participants (N = 283; 96% male, 75%, 57% severe TBI)., Design: Prospective observational cohort., Main Measures: Rehabilitation Needs Survey (21-item survey that assesses cognitive, emotional, social, and functional needs); Craig Hospital Inventory of Environmental Factors (25-item survey of potential environmental barriers)., Results: Participants endorsed a mean of 8 (SD: 6.2) ongoing and 3 (SD: 4.7) unmet rehabilitation needs at 5 years post-TBI. Approximately 65% of participants reported at least 1 rehabilitation need that remained unmet. The number and nature of needs differed across TBI severity groups. In unadjusted and adjusted linear regression models, Black race and environmental barriers (Craig Hospital Inventory of Environmental Factors total score) were predictive of unmet needs (P < .001). Those with greater unmet needs reported the physical environment (54%-63%), informational sources (54%), social attitudes (55%), healthcare access (40%), public policy (32%-37%), transportation availability (33%), and in-home assistance (32%) as the most frequent environmental barriers at 5 years post-TBI., Conclusion: Veterans and Service Members continue to have rehabilitation needs at 5 years post-TBI. Veterans Affairs programs to address ongoing needs and policy to support them are needed., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The present study is to investigate whether extranodal (EN) metabolic tumor volume (MTV) would have a specific clinical meaning for survival in EN diffuse large B cell lymphoma (DLBCL) patients. Two hundred forty DLBCL patients with EN involvement received 18F-fluorodeoxygenase (FDG) positron emission tomography/computed tomography (PET/CT) were enrolled. Survival analysis revealed that low EN MTV (PFS [progression-free survival], HR = 0.278, 95% CI = 0.127-0.807, p = 0.001; OS [overall survival], HR = 0.320, 95% CI = 0.145-0.703, p = 0.003), low total MTV (PFS, HR = 0.194, 95% CI = 0.085-0.445, p < 0.001; OS, HR = 0.213, 95% CI = 0.092-0.491, p < 0.007), and high National Cancer Center Network-International Prognostic Index score (PFS, HR = 3.152, 95% CI = 1.732-5.734, p < 0.001; OS, HR = 2.457, 95% CI = 1.363-4.430, p = 0.003) were independently associated with survivals in the patients. Our data showed that EN MTV is a useful and novel prognostic parameter for predicting survival in DLBCL patients with EN involvement.

A new strategy for the fluorescent and colorimetric sensing of hydrogen peroxide (H 2 O 2 ) and glucose based on the metal oxide - carbon-dot hybrid structure was investigated. The sensing system is related to the catalytic oxidation reaction of glucose-by-glucose oxidase (GOx) to H 2 O 2 . In this study, a metal oxide hybrid with nitrogen-doped carbon dots (MFNCDs) that showed intrinsic peroxidase-like activity was synthesized and used as a catalyst instead of GOx to oxidize 3,3',5,5'-tetramethylbenzidine (TMB) to blue-emitting oxidized TMB (oxTMB) in the presence of hydrogen peroxide (H 2 O 2 ). The fluorescence of MFNCDs/TMB at 405 nm was quenched in the presence of H 2 O 2 through the inner filter effect (IFE) and electron transfer within MFNCDs, oxTMB, and glucose system. Therefore, the fluorescence and absorbance intensity can be applied to the quantitative determination of the concentration of H 2 O 2 and glucose with a wide linear range. The detection limit for H 2 O 2 and glucose based on the colorimetric method were as low as 84 nM and 0.41 μM, respectively. In contrast, the detection limit for H 2 O 2 and glucose based on the fluorescent method were as low as 97 nM and 0.85 μM, respectively. Furthermore, the colorimetric readout on the paper device based on the changing color of the solution could also be integrated with a smartphone platform to conduct the on-site analysis of glucose without the use of the spectrometer. In addition, this dual sensor can be applied to detect glucose in real serum with highly accurate results, making it a good candidate for biosensor applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We aimed to isolate circulating tumor cells (CTCs) using a microfluidic technique with a novel lateral magnetophoretic microseparator. Prostate cancer-specific gene expressions were evaluated using mRNA from the isolated CTCs. A CTC-based multigene model was then developed for identifying advanced prostate cancer. Peripheral blood samples were obtained from five healthy donors and patients with localized prostate cancer (26 cases), metastatic hormone-sensitive prostate cancer (mHSPC, 10 cases), and metastatic castration-resistant prostate cancer (mCRPC, 28 cases). CTC recovery rate and purity (enriched CTCs/total cells) were evaluated according to cancer stage. The areas under the curves of the six gene expressions were used to evaluate whether multigene models could identify mHSPC or mCRPC. The number of CTCs and their purity increased at more advanced cancer stages. In mHSPC/mCRPC cases, the specimens had an average of 27.5 CTCs/mL blood, which was 4.2 × higher than the isolation rate for localized disease. The CTC purity increased from 2.1% for localized disease to 3.8% for mHSPC and 6.7% for mCRPC, with increased CTC expression of the genes encoding prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), and cytokeratin 19 (KRT19). All disease stages exhibited expression of the genes encoding androgen receptor (AR) and epithelial cell adhesion molecule (EpCAM), although expression of the AR-V7 variant was relatively rare. Relative to each gene alone, the multigene model had better accuracy for predicting advanced prostate cancer. Our lateral magnetophoretic microseparator can be used for identifying prostate cancer biomarkers. In addition, CTC-based genetic signatures may guide the early diagnosis of advanced prostate cancer., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Purpose: It remains unclear whether a short warm ischemic time (WIT) improves long-term renal function after partial nephrectomy (PN) for patients with pre-existing chronic kidney disease (CKD). We evaluated renal function after PN according to WIT duration in patients with stage III CKD., Materials and Methods: We identified 277 patients with stage III CKD who underwent PN during 2004-2017. Propensity score matching was used to created two matched groups of patients: Group A (WIT of <25 min) and Group B (WIT of ≥25 min). The outcomes of interest were longitudinal kidney function change, new-onset stage IV CKD (eGFR <30 mL/min/1.73 m 2 ) and overall survival., Results: The two matched groups contained 85 patients each. The median follow-up durations were 49 months in Group A and 42 months in Group B. The median pre-treatment eGFRs were 52.4 mL/min/1.73 m 2 in Group A and 52.6 mL/min/1.73 m 2 in Group B. There were no differences in kidney function between the two groups throughout the follow-up period (P > 0.05). The 5-year rates of new-onset stage IV CKD were not significantly different between Group A and Group B (8.2% vs. 7.1%), with no significant difference in the risk of developing stage IV CKD in Group A (vs. group B, hazard ratio: 0.527, 95% confidence interval: 0.183-1.521; P = 0.236). The 5-year overall survival rates were 90.3% for Group A and 96.2% for Group B (P = 0.549)., Conclusions: A short WIT was not associated with better postoperative kidney function or survival after PN in patients with stage III CKD., Competing Interests: Declaration of competing interest All the authors declare no potential conflict of interest to disclose., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Improving the antibacterial activity of biodegradable materials is crucial for combatting widespread drug-resistant bacteria and plastic pollutants. In this work, we studied polyaniline (PANI)-functionalized zinc oxide nanoparticles (ZnO NPs) to improve surface charges. A PANI-functionalized ZnO NP surface was prepared using a simple impregnation technique. The PANI functionalization of ZnO successfully increased the positive surface charge of the ZnO NPs. In addition, PANI-functionalized ZnO improved mechanical properties and thermal stability. Besides those properties, the water permeability of the bionanocomposite films was decreased due to their increased hydrophobicity. PANI-functionalized ZnO NPs were applied to thermoplastic starch (TPS) films for physical properties and antibacterial studies using Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ). The PANI-functionalized ZnO bionanocomposite films exhibited excellent antibacterial activity for both E. coli (76%) and S. aureus (72%). This result suggests that PANI-functionalized ZnO NPs can improve the antibacterial activity of TPS-based bionanocomposite films.

Herein, a feasible and effective approach is developed to build an electrically conductive and double percolation network-like structure via the incorporation of highly reduced graphene oxide (HRGO) into a polymer blend of diglycidyl ether of bisphenol A/polyetherimide (DGEBA/PEI). With the assistance of the curing reaction-induced phase separation (CRIPS) technique, an interconnected network of HRGO is formed in the phase-separated structure of the DGEBA/PEI polymer blend due to selective localization behavior. In this study, HRGO was prepared from a unique chemical reduction technique. The DGEBA/PEI/HRGO nanocomposite was analyzed in terms of phase structure by content of PEI and low weight fractions of HRGO (0.5 wt.%). The HRGO delivered a high electrical conductivity in DGEBA/PEI polyblends, wherein the value increased from 5.03 × 10 -16 S/m to 5.88 S/m at a low content of HRGO (0.5 wt.%). Furthermore, the HRGO accelerated the curing reaction process of CRIPS due to its amino group. Finally, dynamic mechanical analyses (DMA) were performed to understand the CRIPS phenomenon and selective localization of HRGO reinforcement. The storage modulus increased monotonically from 1536 MPa to 1660 MPa for the 25 phr (parts per hundred in the DGEBA) PEI polyblend and reached 1915 MPa with 0.5 wt.% HRGO reinforcement. These simultaneous improvements in electrical conductivity and dynamic mechanical properties clearly demonstrate the potential of this conductive polyblend for various engineering applications.

In this research, we report the green, blue, and orange color emitting N-doped carbon dots (CDs), which are being synthesized from ascorbic acid and o-/m-/p-phenylenediamine (o-PDA, m-PDA, and p-PDA, respectively). The effects of the solvent polarity and solution pH on the PL emission properties of the as-synthesized CDs have been systematically investigated. It has been observed that the PL emission of the as-synthesized CDs decreases with the increase in solvent polarity due to the greater agglomeration. The surface charge of CDs also shows prominent effects on the pH-dependent PL emission properties.

Purpose: Recently, several studies have demonstrated symptom-based, non-zonal algorithms for approaching penetrating neck injuries. The purpose of this study was to confirm the effectiveness of the "no zone" approach in traumatic neck injuries., Methods: Medical charts of patients with traumatic neck injuries who presented at the Regional Trauma Center in South Korea between January 2014 and December 2018 were retrospectively reviewed. Negative final neck findings (FNFs) were compared with positive FNFs (which include major vascular, aerodigestive, nerve, endocrine gland, cartilage, or hyoid bone injuries) using multivariate logistic regression analysis including values of the "zone" and/or no zone approach., Results: Out of 168 trauma patients, 70 patients with a minor injury and 7 patients under the age of 18 years were excluded. Of the remaining 91 patients, 74 (81.3%) had penetrating neck injuries and 17 (18.7%) had blunt neck injuries. Initial diagnosis most frequently revealed external wounds in zone II (84.6%). Twenty (22.0%) and 36 (39.5%) patients had hard and soft signs, respectively, using the no zone approach. Further, there was a significant difference between the negative and positive FNFs in patients with hard signs (11.6% vs. 54.5%; P < 0.01, respectively). According to the multivariate logistic regression analysis, the hard signs were associated with an odds ratio (OR) for FNFs (OR, 18.92; 95% confidence interval, 3.55-157.60)., Conclusion: Traumatic neck injuries classified as having hard signs based on the no zone approach may be correlated with internal organ injuries of the neck., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2020, the Korean Surgical Society.)

Eukaryotic genome sequencing and de novo assembly, once the exclusive domain of well-funded international consortia, have become increasingly affordable, thus fitting the budgets of individual research groups. Third-generation long-read DNA sequencing technologies are increasingly used, providing extensive genomic toolkits that were once reserved for a few select model organisms. Generating high-quality genome assemblies and annotations for many aquatic species still presents significant challenges due to their large genome sizes, complexity, and high chromosome numbers. Indeed, selecting the most appropriate sequencing and software platforms and annotation pipelines for a new genome project can be daunting because tools often only work in limited contexts. In genomics, generating a high-quality genome assembly/annotation has become an indispensable tool for better understanding the biology of any species. Herein, we state 12 steps to help researchers get started in genome projects by presenting guidelines that are broadly applicable (to any species), sustainable over time, and cover all aspects of genome assembly and annotation projects from start to finish. We review some commonly used approaches, including practical methods to extract high-quality DNA and choices for the best sequencing platforms and library preparations. In addition, we discuss the range of potential bioinformatics pipelines, including structural and functional annotations (e.g., transposable elements and repetitive sequences). This paper also includes information on how to build a wide community for a genome project, the importance of data management, and how to make the data and results Findable, Accessible, Interoperable, and Reusable (FAIR) by submitting them to a public repository and sharing them with the research community., Competing Interests: The authors have declared that no competing interests exist.

Background: Inappropriate antibiotics use and antimicrobial resistance (AMR) are increasingly becoming global health issues of great concern. Despite the established antibiotic stewardship programmes (ASPs) in many countries, limited efforts have been made to engage nurses and clearly define their roles in ASPs., Aim: An exploratory qualitative study was conducted to understand the facilitators and barriers that impact nurses' involvement and empowerment in antibiotic stewardship., Methods: Focus group discussions (FGDs) were conducted with purposively sampled nurses from three major public hospitals in Singapore. FGDs were audio-recorded and transcribed verbatim. Data were analysed using Applied Thematic Analysis and interpreted using the Social Ecological Model., Findings: At the intrapersonal level, nurses felt empowered in carrying out their roles in antibiotic administration. They saw themselves as gatekeepers to ensure that the prescribed antibiotics were administered appropriately. However, nurses felt they lacked the knowledge and expertise in antibiotic use and AMR prevention. At the interpersonal level, this deficit in knowledge and expertise in antibiotic use impacted how they were perceived by patients and caregivers as well as their interactions with the primary care team when voicing outpatient safety concerns and antibiotic administration suggestions. At the organizational level, nurses relied on drug administration guidelines to ensure appropriate antibiotic administration and as a safety net when physicians questioned their clinical practice. At the community level, nurses felt there was a lack of awareness and knowledge on antibiotic use among the general population., Conclusion: These findings provide important insights to harness the contributions of nurses, and to formally acknowledge and enlarge their roles in ASPs., (Copyright © 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Circulating tumor cells (CTCs) are important biomarkers for the diagnosis, prognosis, and treatment of cancer. However, because of their extreme rarity, a more precise technique for isolating CTCs is required to gain deeper insight into the characteristics of cancer. This study compares the performance of a lateral magnetophoretic microseparator ("CTC-μChip"), as a representative microfluidic device, and AdnaTest ProstateCancer (Qiagen), as a commercially available specialized method, for isolating CTCs from the blood of patients with prostate cancer. The enumeration and genetic analysis results of CTCs isolated via the two methods were compared under identical conditions. In the CTC enumeration experiment, the number of CTCs isolated by the CTC-μChip averaged 17.67 CTCs/mL, compared to 1.56 CTCs/mL by the AdnaTest. The number of contaminating white blood cells (WBCs) and the CTC purity with the CTC-μChip averaged 772.22 WBCs/mL and 3.91%, respectively, whereas those with the AdnaTest averaged 67.34 WBCs/mL and 1.98%, respectively. Through genetic analysis, using a cancer-specific gene panel (AR (androgen receptor), AR-V7 (A\androgen receptor variant-7), PSMA (prostate specific membrane antigen), KRT19 (cytokeratin-19), CD45 (PTPRC, Protein tyrosine phosphatase, receptor type, C)) with reverse transcription droplet digital PCR, three genes (AR, AR-V7, and PSMA) were more highly expressed in cells isolated by the CTC-μChip, while KRT19 and CD45 were similarly detected using both methods. Consequently, this study showed that the CTC-μChip can be used to isolate CTCs more reliably than AdnaTest ProstateCancer, as a specialized method for gene analysis of prostate CTCs, as well as more sensitively obtain cancer-associated gene expressions.

Introduction: Coronavirus Disease 2019 (COVID-19) has significantly affected the way healthcare is delivered in Singapore. Healthcare services such as renal transplantation had to rapidly adjust and meet the needs to (1) protect patients and staff, (2) ramp up, conserve or redeploy resources while (3) ensuring that critical services remained operational. This paper aims to describe the experience of the renal transplant programme at the Singapore General Hospital (SGH) in responding to the risks and constraints posed by the pandemic., Methods and Materials: This is a review and summary of the SGH renal transplant programme's policy and protocols that were either modified or developed in response to the COVID-19 Pandemic., Results: A multi-pronged approach was adopted to respond to the challenges of COVID-19. These included ensuring business continuity by splitting the transplant team into different locations, adopting video and tele-consults to minimise potential patient exposure to COVID-19, streamlining work processes using electronic forms, ensuring safe paths for patients who needed to come to hospital, ring-fencing and testing new inpatients at risk for COVID-19, enhancing precautionary measures for transplant surgery, ensuring a stable supply chain of immunosuppression, and sustaining patient and staff education programmes via video conferencing., Conclusions: Though the COVID-19 pandemic has reduced access to kidney transplantation, opportunities arose to adopt telemedicine into mainstream transplant practice as well as use electronic platforms to streamline work processes. Screening protocols were established to ensure that transplantation could be performed safely, while webinars reached out to empower patients to take precautions against COVID-19.

Objectives: Compared to adults, adolescents tend to prefer evening times developmentally. The orientation toward evening times is associated with behavioral and emotional problems. Thus, this study examined the association of circadian preference with sleep-related variables, depression, anxiety, and Internet addiction in Korean adolescents., Materials and Methods: Participants completed the questionnaires measuring sleep pattern, sleep problem, depression, anxiety, and Internet addiction., Results: Among 765 students (age range: 13-17 years), 211 students ( N male = 134) were allocated into morning types (MT) and 258 adolescents ( N male = 147) were allocated into evening types (ET) based on scores of the Morningness-Eveningness Scale. Adolescents without circadian preference ( N = 296) were defined as neither type (NT). ET, compared to MT and NT, woke up later in the weekend, showed delays in bedtimes, and spent shorter time sleeping. They also reported a higher level of daytime sleepiness, insomnia, and depression than NT. However, the group difference in wake time on school days was not significant, and adolescents showed mild insomnia regardless of their circadian preference. Although smartphone using time in the weekend was significantly different between groups, group difference in Internet addiction was significant only when gender was adjusted., Conclusion: Circadian preference was associated with sleep patterns and sleep problems in Korean adolescents. ET showed significantly different sleep patterns compared to MT and NT. ET not only reported a higher level of daytime sleepiness and insomnia but also more depressive symptoms compared to NT. These findings suggest that the uniqueness of adolescence and environmental factors seemed to influence the association of circadian preference with mental problem., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Indian Journal of Psychiatry.)

The burrowing crab Neohelice granulata is a key omnivorous species in intertidal areas along the southwestern Atlantic from southern Brazil to northern Argentinean Patagonia. This crab is adapted to starvation and can endure natural periods of food deprivation. The metabolic adjustments during starvation depend on the type of diet the crabs were fed previously. Since eyestalk-crustacean hyperglycemic hormone (CHH) is the principal regulator of glucose homeostasis in decapods, we investigated whether CHH transcription was affected by diet composition and starvation. Crabs were maintained in the laboratory for two weeks and subsequently divided in two groups. One received a high carbohydrate (HC) diet, and the other was fed a high protein (HP) diet. After this period, they were starved for four weeks. The full-length cDNA sequence of N. granulata CHH was determined and aligned with CHH sequences of other crabs. Levels of circulating glucose and glycogen were higher in the hepatopancreas and muscle of the HC-fed group and decreased after starvation. Glucose and glycogen concentrations were not altered by starvation in the HP group. Triglyceride levels within the hemolymph were not altered by diet or starvation. However, triglycerides concentration was higher in the hepatopancreas of HC compared to HP-fed group. Long-term starvation and diet composition did not affect CHH transcription., (Copyright © 2020 Elsevier Inc. All rights reserved.)

New classification systems based on molecular features have been introduced to improve precision medicine for prostate cancer (PCa). This review covers the increasing risk of PCa and the differences in response to targeted therapy that are related to specific gene variations. We believe that genomic evaluations will be useful for guiding PCa risk stratification, screening, and treatment. We searched the PubMed and MEDLINE databases for articles related to genomic testing for PCa that were published in 2020 or earlier. There is increasing evidence that germline mutations in DNA repair genes, such as BRCA1/2 or ATM , are closely related to the development and aggressiveness of PCa. Targeted prostate-specific antigen screening based on the presence of germline alterations in DNA repair genes is recommend to achieve an early diagnosis of PCa. In cases of localized PCa, even if it has a favorable risk classification, patients under active surveillance with these gene alterations are likely to develop aggressive PCa. Thus, active treatment may be preferable to active surveillance for these patients. In cases of metastatic castration-resistant PCa, BRCA1/2 and DNA mismatch repair genes may be useful biomarkers for predicting the response to androgen receptor-targeting agents, poly (ADP-ribose) polymerase inhibitors, platinum chemotherapy, prostate-specific membrane antigen-targeted therapy, immunotherapy, and radium-223. Genomic evaluations may allow for risk stratification of patients with PCa based on their molecular features, which may help guide precision medicine for treating PCa., Competing Interests: All the authors declare no potential conflict of interest to disclose., (© 2020 Asian Pacific Prostate Society. Publishing services by Elsevier B.V.)

High performance sensors can be produced by adequately designing the chemical structure and uncovering the actual detection mechanism. In this study, a fluorescent probe was synthesized for various nitroaromatic molecules, including stereochemically varied nitrophenols and nitroaniline. A systematic investigation of the influence of various analytes on the luminescence behavior of the as-synthesized carbon dot (CDs) revealed the inner-filter effect to be the major detection mechanism. The extinction coefficient and spectral overlap were found to be the critical parameters for high sensitivity and good selectivity rather than the functional groups of the CDs and analytes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: There is a concern that enhanced recovery after surgery may affect other proposed quality measures, including the rate of readmission due to early discharge. We examine the 30-day readmission rate, risk factors associated with readmission after elective colorectal surgery for colon cancer, causes of readmission, disease-free survival (DFS), and overall survival (OS) in a single institution., Methods: We retrospectively investigated 292 patients who underwent elective colorectal surgery for colon cancer between 2010 and 2015. Baseline data including age, sex, body mass index, American Society of Anesthesiologists physical status classification, preoperative comorbidities, previous operation history, TNM stage, surgical approach, operation time, gas passage time, and length of hospital stay were obtained. Univariate and multivariate logistic regression analyses were performed to identify risk factors associated with 30-day readmission., Results: A total of 229 patients who underwent elective colorectal surgery were enrolled. Twenty-four patients were readmitted 30 days after discharge. The most common readmission diagnoses were wound bleeding or surgical site infection. Multivariate analysis indicated that patients who had preoperative hepatic disease were at the highest risk of readmission (odds ratio [OR], 8.98; 95% confidence interval [CI], 7.35-10.61). Survival outcomes were significantly better in the nonreadmitted group (OS, P=0.00; DFS, P=0.04)., Conclusion: This study identified that preoperative comorbidities including hepatic and pulmonary diseases were associated with higher readmission rates after elective colorectal surgery. Moreover, the most common cause of readmission in patients who underwent elective colorectal surgery was wound bleeding or surgical site infection.

Background: Acutely decompensated heart failure presents a complicated challenge. Established temporary support measures have significant adverse effects. A minimally invasive temporary left ventricular assist device (LVAD), the Impella 5.0 (Abiomed, Danvers, MA), has been developed to support these patients., Methods: Patients with acutely decompensated heart failure in whom medical management had failed and who required additional support using an Impella 5.0 device were evaluated from January 2014 to September 2018 at a single center in a retrospective manner using a prospectively maintained database. Patients were treated with the device as a bridge to recovery (BTR; n = 30), bridge to durable device (BTDD; n = 23), or bridge to transplantation (BTT; n = 47). All devices were placed using an axillary artery approach. Demographic features and outcomes were evaluated for each group and compared., Results: A total of 100 patients underwent insertion of an axillary Impella 5.0 LVAD. Patients had an average age of 56.7 ± 13.2 years, were predominantly male (84%), and had a severely depressed left ventricular ejection fraction (average 16%), and most had an Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 (57%) or 2 (33%) score. When divided into groups, there was no difference in age or INTERMACS score, but a statistical difference was noted in baseline left ventricular ejection fraction (20%, 14%, 15%) and creatinine level (1.0, 2.0, 1.6), in the BTR, BTDD, or BTT group, respectively (all P < .05). Survival was 64% overall, and it was 50%, 48%, and 81% for BTR, BTDD, and BTT, respectively (P = .007). Survival improved during this experience and was 90% overall in the most recent 30 patients., Conclusions: Use of this minimally invasive LVAD system is an attractive strategy to support patients with acute decompensated heart failure to recovery, durable LVAD, or heart transplantation., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Wnt signaling has been implicated as a driver of prostate cancer-related osteoblast differentiation, and previous studies have linked modifications in Wnt function with the induction of tumor metastasis. A unique aspect of prostate cancer bone metastases in mouse models is their relative predilection to the hindlimb (femur) compared to the forelimb (humerus). Comparative gene expression profiling was performed within the humerus and femur from non-tumor-bearing mice to evaluate differences in the microenvironments of these locations. This revealed the relative overexpression of the Wnt signaling inhibitors WIF1 and SOST in the humerus compared to the femur, with increased WNT5A expression in femur bone marrow, suggesting a coordinated upregulation of Wnt signals within the femur compared to the humerus. Conditioned medium (CM) from bone marrow stromal cells (HS-5 cells) was used to mimic the bone marrow microenvironment, which strongly promoted prostate cancer cell invasion (3.3-fold increase in PC3 cells, P < .05; 7-fold increase in LNCaP cells, P < .05). WNT5A shRNA knockdown within the CM-producing HS-5 cells significantly decreased PC3 (56%, P < .05) and LNCaP (60%, P < .05) cell invasion. Similarly, preincubation of CM with WIF1 significantly blocked LNCaP cell invasion (40%, P < .05). shRNA-mediated knockdown of the Wnt receptors FZD4 and FZD8 also strongly inhibited tumor cell invasion (60% inhibition shFZD4, P < .05; 63% shFZD8, P < .05). Furthermore, small molecule inhibition of JNK, which is an important component of the noncanonical Wnt signaling pathway, significantly inhibited CM-mediated tumor invasion. Overall, this study reveals a role for Wnt signaling as a driver of prostate cancer bone metastatic tropism and invasion., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

In the phase 3 study RERISE, patients with newly diagnosed chronic myeloid leukaemia in chronic phase demonstrated significantly faster and higher rates of major molecular response (MMR) with twice-daily radotinib 300 mg (n = 79) or 400 mg (n = 81) than with once-daily imatinib 400 mg (n = 81) after 12 months. With ≥48 months' follow-up, MMR was higher with radotinib 300 mg (86%) or 400 mg (83%) than with imatinib (75%). Among patients with BCR-ABL1 ≤ 10% at three months, MMR and molecular response 4·5 (MR 4·5 ) were achieved within 48 months by more radotinib-treated patients (300 mg: 84% and 52%, respectively; 400 mg: 74% and 44%, respectively) than imatinib-treated patients (71% and 44%, respectively). Estimated overall and progression-free survival rates at 48 months were not significantly different between imatinib (94% and 94%, respectively) and radotinib 300 mg (99% and 97%, respectively) or 400 mg (95% and 93%, respectively). The treatment failure rate was significantly higher with imatinib (19%) than with radotinib 300 mg (6%; P = 0·0197) or 400 mg (5%; P = 0·0072). Safety profiles were consistent with previous reports; most adverse events occurred within 12 months. Radotinib continues to demonstrate robust, deep molecular responses, suggesting that treatment-free remission may be attainable., (© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Autologous stem cell transplant (ASCT) is an effective treatment for non-Hodgkin lymphoma (NHL). However, recent supply issues and toxicity of carmustine have necessitated a new conditioning regimen. We conducted a multicenter, phase II study of BEB (busulfan, etoposide, and bendamustine) conditioning regimen for ASCT in patients with NHL. Thirty-one patients were enrolled and underwent ASCT with the BEB conditioning regimen. The most common subtype was diffuse large B-cell lymphoma (n = 23, 74.2%). Nine patients (29.0%) had a history of relapse, and 18 patients (58.1%) received more than 2 lines of chemotherapy before ASCT. A median number of 6.05 × 10 6 /kg CD34 cells were infused, and all patients engrafted after a median period of 11 days. Thirteen patients (41.9%) experienced neutropenic fever, and 16 patients (51.6%) had grade 3 or 4 toxicities during ASCT. No one had a documented infection, veno-occlusive disease, or treatment-related death. Three-month complete remission rate was 81.8%. Median follow-up period of 15 months showed 6 patients (19.4%) relapsed or progressed and 3 patients died. The estimated 2-year progression-free survival and overall survival rate were 73.0% and 89.8%, respectively. Our results show that BEB conditioning regimens for ASCT are feasible with tolerable toxicity in patients with NHL.

Primary Objective : Research focused on mild traumatic brain injury in active military and veteran populations details the psychological, neurological and functional outcomes of mTBI, in a primarily male (~95%) cohort. This may misrepresent female symptoms and outcomes. Here we assess for genuine sex differences in symptom presentation and functional outcomes. Research Design : We used matched pairs to preclude potential sex bias in outcome data. Methods and Procedures : We matched 49 female/male pairs on; 1) mechanism of injury, 2) time from injury to assessment and 3) age at assessment. Statistics were t-tests, chi-square, correlations and post hoc linear regression. Main outcomes and results : Outcome assessment revealed four significant ( p < .05) sex differences; Living situation, Marital status, Vocation and Branch of service. Only the Neurobehavioral Symptom Inventory (NSI) composite cognitive domain factor was significantly different between females (mean: 10.26) and males (mean: 7.58). Linear regression confirmed a significant effect of sex for the cognitive composite ( p = .002). Conclusion : We conclude that sex has a moderate effect on mTBI post-concussive symptom presentation. The significant sex difference in the NSI cognitive domain characterizes sex-related symptomology profiles providers can focus on for better rehabilitation management. Replication in the larger cohort would improve generalizability. Abbreviation: TBI: Traumatic Brain Injuries; mTBI: mild Traumatic Brain Injuries; OIF: Operation Iraqi Freedom; OEF: Operation Enduring Freedom; VA: Veterans Affairs Health Care System; PSC: Polytrauma System of Care; PRC: Polytrauma Rehabilitation Center; PTRP: Polytrauma Transitional Rehabilitation Program; PNS: Polytrauma Network Site; PTSD: Post Traumatic Stress Disorder; DoD: Department of Defense; NSI: Neurobehavioral Symptom Inventory; LOC: loss of consciousness; AOC: alteration of consciousness; PTA: posttraumatic amnesia; CPRS: computerized patient record system; CTBIE: Comprehensive TBI Evaluation; OCD: obsessive compulsive disorder; ETOH: alcohol abuse.

Purpose: Immune checkpoint inhibitors (ICI) benefit only a minority of treated patients with cancer. Identification of biomarkers distinguishing responders and nonresponders will improve management of patients with cancer. Because the DC-HIL checkpoint differs from the PD1 pathway in expression and inhibitory mechanisms, we examined whether DC-HIL expression regulates ICI responsiveness., Experimental Design: Plasma samples were collected from patients with advanced non-small cell lung carcinoma (NSCLC) ( n = 76) at baseline and/or follow-up after ICI monotherapy. Blood-soluble DC-HIL (sDC-HIL) was determined and analyzed for correlation with the early tumor response. To study the mechanisms, we measured effect of anti-DC-HIL versus anti-PDL1 mAb on growth of mouse tumor cells in experimentally metastatic lung. Influence of DC-HIL to anti-PDL1 treatment was assessed by changes in tumor response after deletion of host- DC-HIL gene, injection of DC-HIL-expressing myeloid-derived suppressor cells (MDSC), or induction of sDC-HIL expression., Results: Nonresponders expressed significantly higher levels of baseline sDC-HIL levels than responders. Among patients ( n = 28) for fluctuation with time, nonresponders (14/15 cases) showed increasing or persistently elevated levels. Responders (12/13) had decreasing or persistently low levels. Among various tumors, B16 melanoma exhibited resistance to anti-PDL1 but responded to anti-DC-HIL mAb. Using B16 melanoma and LL2 lung cancer, we showed that deletion of host-derived DC-HIL expression converted the resistant tumor to one responsive to anti-PDL1 mAb. The responsive state was reversed by infusion of DC-HIL + MDSC or induction of sDC-HIL expression., Conclusions: sDC-HIL in the blood and probably DC-HIL receptor expressed by MDSC play an important role in regulating response to ICI in advanced NSCLC., (©2019 American Association for Cancer Research.)

Background: In young athletes, patient-reported activity level is frequently used to determine return to the same level of sport after treatment., Purpose: To evaluate the validity and score distributions of the Hospital for Special Surgery Pediatric Functional Activity Brief Scale (HSS Pedi-FABS) compared with the Tegner Activity Level Scale (Tegner) in pediatric athletes., Study Design: Cohort study (Diagnosis); Level of evidence, 2., Methods: A retrospective review of 517 consecutive youth athletes who came to a sports medicine specialty clinic for a knee evaluation was performed. Patients completed the HSS Pedi-FABS, Tegner, and a sports participation survey before evaluation. Scores were compared with reported hours, days, and weeks of participation in sports as well as level of competition. Floor or ceiling effects were identified, and finally, the means and distributions of scores in the 8 most common primary sports were analyzed., Results: A total of 398 participants (54.0% female) with an average age of 14.5 years (range, 10.0-18.8 years) were included in the study. The HSS Pedi-FABS demonstrated correlations with hours per week ( r = 0.302; P < .001), days per week ( r = 0.278; P < .001), and weeks per year ( r = 0.136; P = .014) playing a primary sport. The Tegner only demonstrated a correlation with days per week ( r = 0.211; P = .001). Additionally, club/select-level athletes scored higher than junior high/high school-level athletes on the HSS Pedi-FABS (23.8 vs 21.0; P = .004), but no difference was observed with the Tegner. No floor or ceiling effect was observed for the HSS Pedi-FABS, but a ceiling effect was present for the Tegner (32.8%). The HSS Pedi-FABS demonstrated a varied score distribution between the 8 most common primary sports ( P < .001), with soccer players scoring the highest, on average (23.5)., Conclusion: The HSS Pedi-FABS, compared with the Tegner, demonstrated more correlations with an athlete's participation in sport with no floor or ceiling effect and had a wide distribution of scores even among same-sport athletes. The HSS Pedi-FABS may be a more valuable activity measure than the Tegner in pediatric athletes.

Heart failure is a complex, growing problem with significant morbidity and mortality. Though heart transplantation remains the gold standard treatment for end-stage heart failure, there remains a national shortage of donor hearts. Mechanical circulatory support has provided an additional option for clinicians to support patients for the purposes of bridging patients to transplantation or to be used for destination therapy purposes. Despite generally favorable outcomes with univentricular support, in a subset of patients with biventricular heart failure, an isolated left ventricular assist device is not sufficient. Right ventricular failure has a negative impact on patient survival if not identified and treated promptly. The Total Artificial Heart (TAH) is the only Food and Drug Administration (FDA) approved artificial heart used for bridging patients to transplantation. Outcomes in patients who undergo implantation of the TAH at experienced centers have been good and reproducible., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Annals of Cardiothoracic Surgery. All rights reserved.)