tbuckley/cabot-search huggingface dataset:
Abstract 14162: NLRP3 Inflammasome Activation Initiated Through Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKIIδ) Signaling in Cardiomyocytes is Essential for Pressure Overload-Induced Adverse Cardiac Remodeling
Authors: Takeshi Suetomi, Andrew Willeford, Cameron Brand, Shigeki Miyamoto, Joan H Brown
Journal: Circulation (2018)

Introduction and Hypothesis: Inflammation is associated with cardiac remodeling in response to pressure overload, but how it is initiated in the absence of cell death is not known. We tested the hy...
Deferred Cytoreductive Nephrectomy in Patients with Newly Diagnosed Metastatic Renal Cell Carcinoma
Authors: Bimal Bhindi, Jeffrey Graham, J. Connor Wells, Ziad Bakouny, Frede Donskov, Anna Fraccon, Felice Pasini, Jae Lyun Lee, Naveen S. Basappa, Aaron Hansen, Christian K. Kollmannsberger, Ravindran Kanesvaran, Takeshi Yuasa, D. Scott Ernst, Sandy Srinivas, Brian I. Rini, Isaac Bowman, Sumanta K. Pal, Toni K. Choueiri, Daniel Y.C. Heng
Journal: European Urology (2020)
Longitudinal Association Between Markers of Liver Injury and Mortality in COVID‐19 in China
Authors: Fang Lei, Ye‐Mao Liu, Feng Zhou, Juan‐Juan Qin, Peng Zhang, Lihua Zhu, Xiao‐Jing Zhang, Jingjing Cai, Lijin Lin, Shan Ouyang, Xiaoming Wang, Chengzhang Yang, Xu Cheng, Weifang Liu, Haomiao Li, Jing Xie, Bin Wu, Huiming Luo, Fei Xiao, Jing Chen, Liang Tao, Gang Cheng, Zhi‐Gang She, Jianghua Zhou, Haitao Wang, Jun Lin, Pengcheng Luo, Shouzhi Fu, Jihui Zhou, Ping Ye, Bing Xiao, Weiming Mao, Liming Liu, Youqin Yan, Ling Liu, Guohua Chen, Hongliang Li, Xiaodong Huang, Bing‐Hong Zhang, Yufeng Yuan
Journal: Hepatology (2020)

Background and Aims Coronavirus disease 2019 (COVID‐19) is a new infectious disease. To reveal the hepatic injury related to this disease and its clinical significance, we conducted a multicenter retrospective cohort study that included 5,771 adult patients with COVID‐19 pneumonia in Hubei Province. Approach and Results We reported the distributional and temporal patterns of liver injury indicators in these patients and determined their associated factors and death risk. Longitudinal liver function tests were retrospectively analyzed and correlated with the risk factors and death. Liver injury dynamic patterns differed in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL). AST elevated first, followed by ALT, in severe patients. ALP modestly increased during hospitalization and largely remained in the normal range. The fluctuation in TBIL levels was mild in the non‐severe and the severe groups. AST abnormality was associated with the highest mortality risk compared with the other indicators of liver injury during hospitalization. Common factors associated with elevated liver injury indicators were lymphocyte count decrease, neutrophil count increase, and male gender. Conclusion The dynamic patterns of liver injury indicators and their potential risk factors may provide an important explanation for the COVID‐19‐associated liver injury. Because elevated liver injury indicators, particularly AST, are strongly associated with the mortality risk, our study indicates that these parameters should be monitored during hospitalization.
Estimating the global burden of scabies: what else do we need?*
Authors: V. Cox, L.C. Fuller, D. Engelman, A. Steer, R.J. Hay
Journal: British Journal of Dermatology (2020)

Scabies is one of the most common disorders identified in any estimate of global skin disease prevalence. Furthermore, quantifying its impact on individuals and societies has been problematic. There has been a lack of clear case definitions and laboratory tests. There have been few epidemiological studies, particularly those focusing on low-income countries, variation in prevalence within high-income countries, or estimates of the effect of scabies on health beyond the skin, such as renal disease or mental wellbeing. Economic studies are also lacking. However, the new strategy of integrating surveillance for skin Neglected Tropical Diseases may well produce advancements on these issues, in addition to providing an overarching structure for health improvement and disease control.
Endoscopic ultrasound-guided gallbladder drainage as a strategy to overcome shortage of operating rooms and intensive care unit beds during Covid-19 crisis
Authors: Andrea Lisotti, Igor Bacchilega, Romano Linguerri, Pietro Fusaroli
Journal: Endoscopy (2020)

The Covid-19 outbreak has induced dramatic changes to health care in Italy. Restrictions to intensive care units (ICU) and operating rooms to care for Covid-19 patients has limited the facilities available for infection-free patients [1] [2]. We report on a patient with sepsis due to acute cholecystitis who was managed entirely outside the operating room and ICU.
Inhibiting tumor oxygen metabolism and simultaneously generating oxygen by intelligent upconversion nanotherapeutics for enhanced photodynamic therapy
Authors: Dan Wang, Bin Xue, Tymish Y. Ohulchanskyy, Yubin Liu, Artem Yakovliev, Roman Ziniuk, Mengze Xu, Jun Song, Junle Qu, Zhen Yuan
Journal: Biomaterials (2020)
Basaloid follicular proliferations, brain tumours and <i> <scp>SUFU</scp> </i>
Authors: S. Manam, T. Oliphant, A. Husain, N. Rajan
Journal: British Journal of Dermatology (2020)

Dear Editor, The presentation of multiple, benign, hair follicle tumours on the face, infundibulocystic basal cell carcinoma (BCC) and a family history of childhood medulloblastoma is associated with germline mutations in the tumour suppressor gene SUFU (suppressor of fused).1 This patient presented at the age of 42 years with facial (a) and pubic tumours and an absence of jaw cysts; her elder brother had died at 2 years of age with a brain tumour. Biopsy of the perinasal and periocular skin-coloured papules revealed trichoepitheliomas, basaloid follicular hamartomas and trichofolliculoma (b); the pubic tumour was an infundibulocystic BCC (c). Genetic testing revealed a novel pathogenic SUFU mutation (c.1391G>A; p.Trp464*). These families may benefit from predictive genetic testing, which could guide screening for childhood medulloblastoma.2
Early childhood respiratory morbidity and antibiotic use in ex-preterm infants: a primary care population-based cohort study
Authors: Shin Tan, Lisa Szatkowski, William Moreton, Linda Fiaschi, Tricia McKeever, Jack Gibson, Don Sharkey
Journal: European Respiratory Journal (2020)

Background Globally, bronchopulmonary dysplasia (BPD) continues to increase in preterm infants. Recent studies exploring subsequent early childhood respiratory morbidity have been small or focused on hospital admissions. Aims To examine early childhood rates of primary care consultations for respiratory tract infections (RTI), lower respiratory tract infections (LRTI), wheeze and antibiotic prescriptions in ex-preterm and term children. A secondary aim was to examine differences between preterm infants discharged home with or without oxygen. Methods Retrospective cohort study using linked electronic primary care and hospital databases of children born between 1997 and 2014. We included 253 277 eligible children, with 1666 born preterm at &lt;32 weeks' gestation, followed-up from primary care registration to age 5 years. Adjusted incidence rate ratios (aIRRs) were calculated. Results Ex-preterm infants had higher rates of morbidity across all respiratory outcomes. After adjusting for confounders, aIRRs for RTI (1.37, 95% CI 1.33–1.42), LRTI (2.79, 95% CI 2.59–3.01), wheeze (3.05, 95% CI 2.64–3.52) and antibiotic prescriptions (1.49, 95% CI 1.44–1.55) were higher for ex-preterm infants. Ex-preterm infants discharged home on oxygen had significantly greater morbidity across all respiratory diagnoses and antibiotic prescriptions compared to those without home oxygen. The highest rates of respiratory morbidity were observed in children from the most deprived socioeconomic groups. Conclusion Ex-preterm infants, particularly those with BPD requiring home oxygen, have significant respiratory morbidity and antibiotic prescriptions in early childhood. With the increasing prevalence of BPD, further research should focus on strategies to reduce the burden of respiratory morbidity in these high-risk infants after hospital discharge.
A prospective, randomized trial of sclerotherapy versus ligation in the management of bleeding esophageal varices
Authors: G LO
Journal: Hepatology (1995)

We conducted a prospective, randomized trial comparing sclerotherapy and ligation in 120 patients with acute bleeding of esophageal varices. All the patients were cirrhotic, 59 received sclerotherapy, and 61 received ligation. Treatment was repeated regularly until the varices were obliterated. The mean follow-up period was 295 ± 120 days and 310 ± 105 days for the sclerotherapy and ligation groups, respectively. The control of active bleeding was 12/15 (80%) in the sclerotherapy group and 18/19 (94%) in the ligation group (P = .23). The numbers of treatment sessions required to achieve variceal obliteration were 6.5 ± 1.2 in the sclerotherapy group and 3.8 ± 0.4 in the ligation group (P < .001). Recurrent bleeding from the gastrointestinal tract was 51% in the sclerotherapy group compared with 33% in the ligation group (P < .05). Recurrent bleeding from esophageal varices was 36% in the sclerotherapy group and 11% in the ligation group (P < .01). However, bleeding from ectopic varices and congestive gastropathy was less common in the sclerotherapy group (7%) than in the ligation group (18%) (P = .05). Significant complications were encountered in 19% of the sclerotherapy group and in 3.3% of the ligation group (P < .01). Comparison of Kaplan-Meier estimates of time to death of both groups showed a significantly lower mortality in the ligation group (P = .011). Both sclerotherapy and ligation can effectively arrest active bleeding from esophageal varices. However, ligation is more-effective than sclerotherapy in decreasing the risk of rebleeding from esophageal varices with fewer complications. Ligation can also achieve obliteration of esophageal varices more rapidly than sclerotherapy. Survival was significantly more improved after ligation than after sclerotherapy. However, there was a greater incidence of bleeding from sites other than the esophageal varices after ligation. (Hepatology 1995; 22:466–471.)
Concordance between epidemiological evaluation of probability of transmission and whole genome sequence relatedness among hospitalized patients acquiring Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae
Authors: N. Hassoun-Kheir, O. Snitser, K. Hussein, G. Rabino, O. Eluk, S. Warman, W. Aboalhega, Y. Geffen, S. Mendelson, R. Kishony, M. Paul
Journal: Clinical Microbiology and Infection (2020)
Sequential intraventricular injection of tigecycline and polymyxin B in the treatment of intracranial Acinetobacter baumannii infection after trauma: a case report and review of the literature
Authors: Li Zhong, Xue-Zhi Shi, Lei Su, Zhi-Feng Liu
Journal: Military Medical Research (2020)

Intracranial infection after craniotomy is one of the most serious postoperative complications, especially multidrug-resistant (MDR) or extensively drug-resistant (XDR) bacterial meningitis, and strongly affects the prognosis of patients. Current treatment experience regarding these infections is scarce. We report a case of severe intracranial infection of XDR Acinetobacter baumannii (A. baumannii) that was treated by intravenous (IV) injection, sequential intraventricular (IVT) injection of tigecycline and polymyxin B, and other anti-infective drugs. Good results were obtained, and the patient was eventually discharged from the hospital. This case is characterized by intracranial infection. The polymyxin B IV + IVT pathway is an ideal treatment strategy for XDR A. baumannii. The tigecycline IVT pathway is also a safe treatment option.
Growth hormone stimulates proliferation of old-aged regenerating liver through forkhead box m1b
Authors: K Krupczak-Hollis
Journal: Hepatology (2003)

The Forkhead Box (Fox) proteins are an extensive family of transcription factors that shares homology in the winged helix DNA-binding domain and the members of which play essential roles in cellular proliferation, differentiation, and longevity. Reduced cellular proliferation during aging is associated with a progressive decline in both growth hormone (GH) secretion and Foxm1b expression. Liver regeneration studies with 12-month-old (old-aged) transgenic mice indicated that increased hepatocyte expression of Foxm1b alone is sufficient to restore hepatocyte proliferation to levels found in 2-month-old (young) regenerating liver. GH therapy in older people has been shown to cause an increase in cellular proliferation, but the transcription factors that mediated this stimulation in proliferation remain uncharacterized. In this study, we showed that human GH administration to old-aged Balb/c mice dramatically increased both expression of Foxm1b and regenerating hepatocyte proliferation. This increase in old-aged regenerating hepatocyte proliferation was associated with elevated protein expression of Cdc25A, Cdc25B, and cyclin B1, with reduced protein levels of cyclin-dependent kinase inhibitor p27Kip1 (p27). GH treatment also was found to stimulate hepatocyte proliferation and expression of Foxm1b protein without partial hepatectomy (PHx). Furthermore, GH treatment of young Foxm1b −/− mice failed to restore regenerating hepatocyte DNA replication and mitosis caused by Foxm1b deficiency. These genetic studies provided strong evidence that the presence of Foxm1b is essential for GH to stimulate regenerating hepatocyte proliferation. In conclusion, our old-aged liver regeneration studies show that increased Foxm1b levels are essential for GH to stimulate hepatocyte proliferation, thus providing a mechanism for GH action in the elderly. (Hepatology 2003;38:1552-1562.)
High-affinity mutant Interleukin-13 targeted CAR T cells enhance delivery of clickable biodegradable fluorescent nanoparticles to glioblastoma
Authors: Gloria B. Kim, Virginia Aragon-Sanabria, Lauren Randolph, Hali Jiang, Joshua A. Reynolds, Becky S. Webb, Achuthamangalam Madhankumar, Xiaojun Lian, James R. Connor, Jian Yang, Cheng Dong
Journal: Bioactive Materials (2020)

Glioblastoma (GBM), the deadliest form of brain cancer, presents long-standing problems due to its localization. Chimeric antigen receptor (CAR) T cell immunotherapy has emerged as a powerful strategy to treat cancer. IL-13-receptor-α2 (IL13Rα2), present in over 75% of GBMs, has been recognized as an attractive candidate for anti-glioblastoma therapy. Here, we propose a novel multidisciplinary approach to target brain tumors using a combination of fluorescent, therapeutic nanoparticles and CAR T cells modified with a targeted-quadruple-mutant of IL13 (TQM-13) shown to have high binding affinity to IL13Rα2-expressing glioblastoma cells with low off-target toxicity. Azide-alkyne cycloaddition conjugation of nanoparticles to the surface of T cells allowed a facile, selective, and high-yielding clicking of the nanoparticles. Nanoparticles clicked onto T cells were retained for at least 8 days showing that the linkage is stable and promising a suitable time window for
A Randomized Trial Comparing Ceftazidime Alone with Combination Antibiotic Therapy in Cancer Patients with Fever and Neutropenia
Authors: Philip A. Pizzo, James W. Hathorn, John Hiemenz, Marcia Browne, James Commers, Deborah Cotton, Janet Gress, Dan Longo, Doris Marshall, John McKnight, Marc Rubin, Jane Skelton, Michael Thaler, Robert Wesley
Journal: New England Journal of Medicine (1986)

To assess the efficacy of single-agent therapy relative to standard combination antibiotic therapy for the initial management of fever and neutropenia in cancer patients, we conducted a randomized trial comparing ceftazidime alone with a combination of cephalothin, gentamicin, and carbenicillin. Of 550 evaluable episodes of fever and neutropenia, 282 were treated with ceftazidime alone and 268 with the combination. All episodes were evaluated for responses at 72 hours after the start of treatment and at resolution of the neutropenia. Of the patients with unexplained fever who were given ceftazidime alone, 99 percent were alive at 72 hours and 98 percent were alive when the neutropenia resolved, as compared with 100 percent and 98 percent, respectively, of those given combination therapy. Of the patients with documented infection who were given ceftazidime alone, 98 percent were alive at 72 hours and 89 percent when the neutropenia resolved, as compared with 98 percent and 91 percent, respectively, of those given combination therapy. The majority of episodes of documented infection in both treatment groups necessitated additional antimicrobial treatment or other modifications of the initial regimen, as compared with only 22 percent of the episodes of unexplained fever. We conclude that initial single-agent therapy with certain β-lactam antibiotics is a safe alternative to standard combination antibiotic therapy, although patients with documented infection or protracted neutropenia are likely to require additional or modified treatment. (N Engl J Med 1986; 315:552–8.)
C24‐Ceramide Drives Gallbladder Cancer Progression Through Directly Targeting Phosphatidylinositol 5‐Phosphate 4‐Kinase Type‐2 Gamma to Facilitate Mammalian Target of Rapamycin Signaling Activation
Authors: Yonglong Zhang, Hui Wang, Tao Chen, Haolu Wang, Xiaowen Liang, Yuchen Zhang, Jinlin Duan, Shenjiao Qian, Ke Qiao, Lei Zhang, Yanfeng Liu, Jian Wang
Journal: Hepatology (2020)

Background and Aims The wide prevalence of chemoresistance and compromised early diagnosis of gallbladder cancer (GBC) has led to poor patient prognosis, requiring sustained efforts for the identification of effective biomarkers and therapeutic intervention. Ceramides have emerged as intracellular signaling molecules linked to tumorigenesis and therapeutic response in cancers. However, the clinical relevance of ceramides with GBC has not been investigated. Approach and Results In the present study, we revealed aberrant gene expressions (e.g., serine palmitoyltransferase 1 [SPTLC1] and ceramide synthase 2 [CERS2]) of de novo ceramide biosynthesis and length‐specific ceramide production in GBC tissues. Analyses of serum ceramide pattern in healthy controls, gallbladder stone, and GBC patients identified C24‐Ceramide as a potential diagnostic biomarker for patients with GBC. Importantly, elevation of SPTLC1, CERS2, and its product, C24‐Ceramide, was associated with tumor staging, distal metastasis, and worse prognosis. In line with this, C 24 ‐Ceramide promoted GBC cell proliferation and migration in vitro and in vivo . Mechanistically, C24‐Ceramide directly bound to phosphatidylinositol 5‐phosphate 4‐kinase type‐2 gamma (PIP4K2C), a regulator of mammalian target of rapamycin (mTOR), to facilitate mTOR complex formation and activation. C6‐Ceramide, an analogue of natural ceramide, competed with C24‐Ceramide for PIP4K2C binding, thereby abrogating C24‐Ceramide–mediated mTOR signaling activation and oncogenic activity. Furthermore, stimulation with C6‐Ceramide significantly suppressed the proliferative and metastatic capacity of GBC cells in vitro and in vivo , which was dependent on PIP4K2C. Conclusions Our findings highlight the clinical relevance of ceramide metabolism with GBC progression and identify C24‐Ceramide as a diagnostic biomarker for GBC. We propose that PIP4K2C is indispensable for C6‐Ceramide as a potential therapeutic intervention for GBC through a direct competition with C24‐Ceramide.
Instability of Insulin Aspart Diluted in Dextrose
Authors: Laure-Hélène Préta, Héloïse Henry, Morgane Masse, Christine Barthélémy, Natacha Carta, Catherine Foulon, Jean-François Goossens, Mostafa Kouach, Damien Lannoy, Laurent Storme, Bertrand Décaudin, Stéphanie Genay, Pascal Odou
Journal: Diabetes Care (2020)

Insulin aspart (Novorapid) is a rapid-acting insulin analog that is maintained in hexameric form by phenolic preservatives (phenol and metacresol) and stabilized by insulin-zinc complex. According to the manufacturers, insulin can be independently diluted either in 5% dextrose solution (D5%) or 0.9% sodium chloride solution. In reality, in most clinical units, such as the neonatal intensive care unit (NICU), insulin aspart is more frequently diluted in D5% than in saline solution due to sodium restriction.

However, injectable dextrose solutions contain glucose degradation products (1) that are capable of binding proteins—like insulin—through a glycation phenomenon. Therefore, dilution of Novorapid in D5% would be more likely to cause glycated insulin and may raise a worrisome problem in terms of insulin stability. The objective of this study was to investigate the stability of insulin aspart diluted in D5% at both adult and neonate therapeutic concentrations in order to ensure its appropriateness in the preparation of insulin aspart.

To address this issue, insulin aspart diluted in D5% was assayed by a stability-indicating method using high-performance liquid chromatography (HPLC) coupled with an ultraviolet (UV) detector. The nature of the formed product was determined by HPLC coupled with a mass spectrometer. The effect of …
509 POTENTIAL UTILITY OF XENOBIOTIC MITOGENS IN THE CONTEXT OF LIVER REGENERATION IN THE ELDERLY AND LIVING-RELATED TRANSPLANTATION
Authors: A. Columbano, M. Simbula, M. Pibiri, A. Perra, A. Pisanu, A. Uccheddu, G.M. Ledda-Columbano
Journal: Journal of Hepatology (2008)
A commentary on the article: Comparison of outcomes after differentiated thyroid cancer surgery performed with and without energy devices: A population-based cohort study using a nationwide database in Japan, Int. J. Surg. 2020 Apr 9, doi: 10.1016/j.ijsu.2020.03.072, pii: S1743-9191(20)30286-7
Authors: Faramarz Karimian
Journal: International Journal of Surgery (2020)
Oral microbiome: possible harbinger for children’s health
Authors: Jin Xiao, Kevin A. Fiscella, Steven R. Gill
Journal: International Journal of Oral Science (2020)

Abstract The human microbiome functions as an intricate and coordinated microbial network, residing throughout the mucosal surfaces of the skin, oral cavity, gastrointestinal tract, respiratory tract, and reproductive system. The oral microbiome encompasses a highly diverse microbiota, consisting of over 700 microorganisms, including bacteria, fungi, and viruses. As our understanding of the relationship between the oral microbiome and human health has evolved, we have identified a diverse array of oral and systemic diseases associated with this microbial community, including but not limited to caries, periodontal diseases, oral cancer, colorectal cancer, pancreatic cancer, and inflammatory bowel syndrome. The potential predictive relationship between the oral microbiota and these human diseases suggests that the oral cavity is an ideal site for disease diagnosis and development of rapid point-of-care tests. The oral cavity is easily accessible with a non-invasive collection of biological samples. We can envision a future where early life salivary diagnostic tools will be used to predict and prevent future disease via analyzing and shaping the infant’s oral microbiome. In this review, we present evidence for the establishment of the oral microbiome during early childhood, the capability of using childhood oral microbiome to predict future oral and systemic diseases, and the limitations of the current evidence.
Niacin Cures Systemic NAD+ Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy
Authors: Eija Pirinen, Mari Auranen, Nahid A. Khan, Virginia Brilhante, Niina Urho, Alberto Pessia, Antti Hakkarainen, Juho Kuula, Ulla Heinonen, Mark S. Schmidt, Kimmo Haimilahti, Päivi Piirilä, Nina Lundbom, Marja-Riitta Taskinen, Charles Brenner, Vidya Velagapudi, Kirsi H. Pietiläinen, Anu Suomalainen
Journal: Cell Metabolism (2020)