bluuebunny/crossref_metadata_2025 huggingface dataset:
Thrombin action on astrocytes in the hindbrain of the rat disrupts glycemic and respiratory control
Authors: Rogers Richard C. , Hasser Eileen M. , Hermann Gerlinda E.
Published: April 2020

Severe trauma can produce a postinjury “metabolic self-destruction” characterized by catabolic metabolism and hyperglycemia. The severity of the hyperglycemia is highly correlated with posttrauma morbidity and mortality. Although no mechanism has been posited to connect severe trauma with a loss of autonomic control over metabolism, traumatic injury causes other failures of autonomic function, notably, gastric stasis and ulceration (“Cushing’s ulcer”), which has been connected with the generation of thrombin. Our previous studies established that proteinase-activated receptors (PAR1; “thrombin receptors”) located on astrocytes in the autonomically critical nucleus of the solitary tract (NST) can modulate gastric control circuit neurons to cause gastric stasis. Hindbrain astrocytes have also been implicated as important detectors of low glucose or glucose utilization. When activated, these astrocytes communicate with hindbrain catecholamine neurons that, in turn, trigger counterregulatory responses (CRR). There may be a convergence between the effects of thrombin to derange hindbrain gastrointestinal control and the hindbrain circuitry that initiates CRR to increase glycemia in reaction to critical hypoglycemia. Our results suggest that thrombin acts within the NST to increase glycemia through an astrocyte-dependent mechanism. Blockade of purinergic gliotransmission pathways interrupted the effect of thrombin to increase glycemia. Our studies also revealed that thrombin, acting in the NST, produced a rapid, dramatic, and potentially lethal suppression of respiratory rhythm that was also a function of purinergic gliotransmission. These results suggest that the critical connection between traumatic injury and a general collapse of autonomic regulation involves thrombin action on astrocytes.
ZiYinHuaTan Recipe Inhibits Cell Proliferation and Promotes Apoptosis in Gastric Cancer by Suppressing PI3K/AKT Pathway
Authors: Yu Jiahui , Song Shangjin , Jiao Jianpeng , Liu Xuan , Zhu Huirong , Xiu Lijuan , Sun Dazhi , Li Qi , Yue Xiaoqiang
Published: April 2020

In recent years, traditional Chinese medicine has played an important role in the treatment of gastric cancer in China. ZiYinHuaTan (ZYHT) recipe was developed for advanced gastric cancer and had shown its promising value in the clinic. In this study, we explore the effect of ZYHT on gastric cancer in vitro and in vivo. ZYHT can inhibit tumor growth and improve the general condition of mice in subcutaneous transplantation nude mice models of gastric cancer. And ZYHT can also inhibit cell proliferation and blocked the cells in G0/G1 to induce cell apoptosis in HGC27 and MGC803 cells. Then, network pharmacology analysis showed that ZYHT may exert antitumor effect mainly through PI3K/AKT signaling pathway. Furthermore, the expression of PI3K, p‐Akt, CyclinD1, and Bcl‐2 was detected in vitro and in vivo. The results showed that ZYHT could decrease the expression of PI3K, CyclinD1, and Bcl‐2 both in vitro and in vivo. These results suggested that ZYHT could be used as a method for the treatment of developed gastric cancer.
Tu-Teng-Cao Extract Alleviates Monosodium Urate‐Induced Acute Gouty Arthritis in Rats by Inhibiting Uric Acid and Inflammation
Authors: Yao Rongmei , Geng Zihan , Mao Xin , Bao Yanyan , Guo Shanshan , Bao Lei , Sun Jing , Gao Yingjie , Xu Yingli , Guo Bo , Meng Fengxian , Cui Xiaolan
Published: April 2020

Gouty arthritis is an inflammatory joint disease closely related to hyperuricemia. It is characterized by deposition of monosodium urate crystals in the joints, resulting in an intense inflammatory process and pain. Control of hyperuricemia and anti‐inflammation treatments are the main therapeutic approaches. However, the commonly used drugs for inhibiting uric acid and acute gouty arthritis have obvious gastrointestinal and renal toxicity; thus, there is an urgency to develop new alternative therapeutic drugs. An extract of Tu-Teng-Cao (TTC), a compound drug used in traditional Chinese medicine, has been widely applied to the clinical treatment of arthritis. In this study, we investigated the therapeutic effects of TTC on gouty arthritis. In this study, an animal model of acute gouty arthritis with hyperuricemia was established using potassium oxonate and monosodium urate crystals. After treatment with TTC, the results showed obvious therapeutic effects on the rat model of acute gouty arthritis. The treatment significantly attenuated the degree of ankle swelling, inflammation, and dysfunction index, and the levels of proinflammatory cytokines. In addition, TTC has significant antihyperuricemia activity in rats with hyperuricemia induced by potassium oxonate. Histological evaluation showed that TTC relieved pathological damage in rats with acute gouty arthritis induced by monosodium urate crystals. All the groups treated with TTC showed improvement in cartilage degeneration, cell degeneration, synovial hyperplasia, and inflammatory cell invasion in the ankle joint of rats. TTC significantly alleviated swelling, inflammation, and bleeding of the renal corpuscle and convoluted tubules of rats. The results of this study suggest that TTC is capable of treating gouty arthritis and decreasing ankle injury through the control of uric acid and inflammation.
The Role of Overexpressed Apolipoprotein AV in Insulin‐Resistant Hepatocytes
Authors: Zhao Wang , Liu Yaqiong , Liao Xiaobo , Zhao Shuiping
Published: April 2020

In this paper, we sought to explore the relationship between apolipoprotein AV (APOAV) overexpression and insulin resistance in hepatocytes. The insulin‐resistant HepG2 cell model was constructed, and then, APOAV‐overexpressed HepG2 cells (B‐M) were induced by infecting with a recombinant adenovirus vector. Microarray data were developed from B‐M samples compared with negative controls (A‐con), and the microarray data were analyzed by bioinformatic methods. APOAV‐overexpression induced 313 upregulated genes and 563 downregulated ones in B‐M sample. The differentially expressed genes (DEGs) were significantly classified in fat digestion and absorption pathway. Protein‐protein interaction network was constructed, and AGTR1 (angiotensin II receptor type 1) and P2RY2 (purinergic receptor P2Y, G‐protein coupled 2) were found to be the significant nodes closely related with G‐protein related signaling. Additionally, overexpression of APOAV could change the expression of Glut4 and release the insulin resistance of hepatic cells. Thus, APOAV overexpression may prevent the insulin resistance in liver cells by mediating the genes such as AGTR1 and P2RY2.
Giant Thrombosis at Left Anterior Descending Artery Aneurysm in a 10-Year Old Boy with Granulomatosis with Polyangiitis
Authors: Aghaei Moghadam Ehsan , Aslani Nahid , Mojtabavi Helia , Larti Farnoosh , Ghamari Azin , Ziaee Vahid
Published: April 2020

Granulomatosis with polyangiitis (GPA), necrotizing vasculitis of small and medium-sized vessels, is traditionally believed to mainly affect respiratory tract with additional focal kidney involvements as its primary manifestations with a relatively rare annual incidence rate of 20-50 cases per million. Six percent of the affected cases have cardiac involvements; among which, aneurysms comprise the lowest penetrance. By this paper, we aim to cast light on clinical diagnostic and treatment methods of a rare case presentation, a 10-year-old male GPA patient, diagnosed with massive thrombosis at his coronary artery aneurysm. GPA should be considered as differential diagnosis of prolong fever and coronary aneurysms in adolescents.
Effect of Shenfu Injection on Porcine Renal Function after Cardiopulmonary Resuscitation
Authors: Zhao Shen , Tang Ziren , Cui Hao , Yang Zhengfei , Shao Fei , Wang Shuo , Chen Feng
Published: April 2020

Objective. To comprehensively evaluate the protective effect of Shenfu injection (SFI) on renal ischaemia/reperfusion injury (IRI) after cardiopulmonary resuscitation (CPR) through neutrophil gelatinase‐associated lipocalin (NGAL) and to explore effective monitoring of early renal injuries after CPR. Methods. Thirty healthy minipigs were randomly divided into 3 groups: sham operation (SO) (n = 6), control (n = 12), and SFI (n = 12). The SO group underwent only catheterization, whereas the control and SFI groups were subjected to program‐controlled electrical stimulation to establish a cardiac arrest (CA) model due to ventricular fibrillation. After CPR, the return of spontaneous circulation was achieved. Each animal in the SFI group was intravenously injected with SFI after resuscitation. Haemodynamic parameters were monitored at baseline and 2, 6, 12, and 24 hr after CPR. At each time point, venous blood samples were collected for NGAL, creatinine, and ATPase screening. Results. After CA, the MAP, CPP, and CO of the animals in the control and SFI groups decreased significantly. However, at 6 hr after CPR, the MAP, CPP, and CO of the animals in the SFI group began to recover gradually; the differences between the control and SFI groups were significant (P < 0.005). The renal damage immediately after CPR appeared to be significant in the pathological examinations. However, the degree of renal injury in the SFI group improved significantly, and the apoptosis index was also notably reduced. The blood and urine NGAL levels were clearly elevated after CPR. The greatest increase in NGAL was found in the control group, which was significantly different from that of the SFI group (P < 0.001). SFI can significantly increase the ATPase activity of kidney tissues after CPR and improve abnormal caspase‐3 protein expression. Conclusion. SFI can effectively prevent acute kidney injuries caused by CPR through improving energy metabolism and inhibiting apoptosis.
Efficient Conversion of Agroindustrial Waste into D(‐) Lactic Acid by Lactobacillus delbrueckii Using Fed‐Batch Fermentation
Authors: Beitel Susan Michelz , Coelho Luciana Fontes , Contiero Jonas
Published: April 2020

Purpose. The goal of this paper is to describe the green conversion of agricultural waste products, such as molasses and corn steep liquor, into large amounts of D(‐) lactic acid using a facilitated multipulse fed‐batch strategy and affordable pH neutralizer. This is a very low‐cost process because there is no need for hydrolysis of the waste products. The fed‐batch strategy increases lactic acid productivity by avoiding inhibition caused by a high initial substrate concentration, and the selected controlling agent prevents cell stress that could be caused by high osmotic pressure of the culture media. Methods. The effects of different carbon and nitrogen sources on lactic acid production were investigated, and the best concentrations of the medium components were determined. To optimize the culture conditions of the Lactobacillus delbrueckii strain, the effects of pH control, temperature, neutralizing agent, agitation, and inoculum size in batch cultures were investigated. Fed‐batch strategies were also studied to improve production and productivity. Result. A high titer of D(‐) lactic acid (162g/liter) was achieved after 48 hours of fermentation. Productivity at this point was 3.37 g/L·h. The optimum conditions were a temperature of 39°C, pH 5.5 controlled by the addition of Ca(OH)2, agitation at 150 rpm, and inoculum size of 25% (v/v). Conclusion. The production of high optical purity D(‐) lactic acid through L. delbrueckii fermentation with molasses and corn steep liquor is a promising economical alternative process that can be performed on the industrial scale.
ALT-to-Lymphocyte Ratio as a Predictor of Long-Term Mortality in Patients with Normal Liver Function Presenting Coronary Artery Disease after Undergoing PCI: A Retrospective Cohort Study
Authors: Zheng Ru-Jie , Guo Qian-Qian , Tang Jun-Nan , Yang Xu-Ming , Zhang Jian-Chao , Cheng Meng-Die , Song Feng-Hua , Liu Zhi-Yu , Wang Kai , Jiang Li-Zhu , Fan Lei , Yue Xiao-Ting , Bai Yan , Dai Xin-Ya , Zhang Zeng-Lei , Zheng Ying-Ying , Zhang Jin-Ying
Published: April 2020

Background. Alanine aminotransferase (ALT) is referred as liver transaminase and predominantly expressed by hepatocytes. Previous evidences showed that high levels of ALT were reversely associated with short- and long-term outcomes in patients with myocardial infarction. Besides, low lymphocyte has been demonstrated to be significantly correlated with adverse clinical outcomes in coronary artery disease (CAD). However, evidences about the relationship between ALT-to-lymphocyte ratio (ALR) and outcomes in CAD patients with normal liver function are limited. The aim of this study was to assess the relationship between ALR and clinical outcomes in patients with CAD. Methods. This is a retrospective cohort study, and a total of 3561 patients were enrolled in Clinical Outcomes and Risk Factors of Patients with CAD after percutaneous coronary intervention (PCI), from January 2013 to December 2017. After excluding patients with liver dysfunction, we finally enrolled 2714 patients. These patients were divided into two groups according to ALR value: the lower group (ALR < 14.06, n = 1804) and the higher group (ALR ≥ 14.06, n = 910). The average follow-up time was 37.59 ± 22.24 months. Results. We found that there were significant differences between the two groups in the incidence of all-cause mortality (ACM) (P<0.001) and cardiac mortality (CM) (P=0.010). Kaplan–Meier survival analysis suggested that CAD patients with higher ALR tended to have an increased accumulated risk of ACM and CM (log rank P<0.001 and P=0.006, respectively). Multivariate Cox regression analysis showed that ALR was an independent predictor of ACM (hazard ratio (HR) = 2.017 (95% confidence interval (CI): 1.289–3.158), P=0.002) and CM (HR = 1.862 (95% CI: 1.047–3.313), P=0.034). We did not find significant difference in the incidence of major adverse cardiovascular events (MACEs) and major adverse cardiovascular and cerebrovascular events (MACCEs) between the two groups after adjustments of confounders. Conclusion. Our results indicate that ALR is an independent predictor of long-term adverse outcomes in CAD patients who underwent PCI.
[Retracted] In Vivo Development of Polymyxin B Resistance in Klebsiella pneumoniae owing to a 42 bp Deletion in the Sequence of phoQ
Authors: Xu Qingqing , Xu Teng , Zhuang Yuan , Liu Xiaofen , Li Ying , Chen Yijian
Published: April 2020

Polymyxins resistance has emerged worldwide and is threatening the treatment efficacy of multidrug resistant Klebsiella pneumoniae in humans and animals. In this research, we employed whole‐genome sequencing (WGS) to investigate the polymyxin B resistance mechanism in selected polymyxin B‐susceptible and polymyxin B‐resistant K. pneumoniae, isolated from one patient of Huashan Hospital affiliated to Fudan University. The WGS results showed that the two K. pneumoniae all belong to ST11. The average nucleotide identity between the two K. pneumoniae was nearly 100%. No sense mutations of polymyxins resistance associated genes (pmrA, pmrB, phoP, mgrB) were observed in polymyxin B‐resistant K. pneumonia (PRKP) compared to the polymyxin B‐susceptible isolate. A 42 bp deletion was found in the sequence of phoQ in PRKP. The deletion of amino acid occurred on the periplasmic domain of PhoQ protein. We speculate that this is the domain that MgrB protein interact with the PhoQ protein and negatively regulate the PhoP/PhoQ system. qRT‐PCR analysis revealed an overexpression of the pmrA (6.8‐fold), pmrB (151.9‐fold), pmrC (14.5‐fold), pmrK (287.9‐fold), phoP (14.5‐fold), and phoQ (16.8‐fold) genes in the polymyxin B‐resistant isolate compared to the expression of the polymyxin B‐susceptible K. pneumoniae isolate, suggesting that the phoQ deletion maybe responsible for the increased expression levels of those genes. In conclusion, this study identified a 42 bp deletion in the sequence of phoQ as being responsible for the overexpression of pmrCAB and pmrHFIJKLM operons, leading to resistance to polymyxin B.
Chinese Herbal Medicines and Conventional Chronic Heart Failure Treatment for the Management of Chronic Heart Failure Complicated with Depression: A Systematic Review and Meta‐Analysis
Authors: Yang Peidan , He Jun
Published: April 2020

Background. Combination therapy with Chinese herbal medicines (CHMs) and conventional medical treatment (CMT) was proposed as a therapeutic strategy for chronic heart failure (CHF) patients complicated with depression. Therefore, we performed a systematic review and meta‐analysis of randomized controlled trials (RCTs) to assess effects of this combination therapy on CHF complicated with depression. Methods. RCTs comparing the combination of CHMs and CMT to CMT were retrieved in seven electrical databases till March 30, 2019. The effective rate of cardiac function and Hamilton depression scale (HAMD) were marked as the primary outcomes. Left ventricular ejection fraction (LVEF) and Minnesota Living with Heart Failure Questionnaire (MLHFQ) were marked as the secondary outcomes. The methodological quality of eligible RCTs used the Cochrane bias risk assessment tool. Stata 13.0 and Review Manager 5.3 were preferred for synthesizing the results if the results were appropriate. Results. Thirteen RCTs enrolling 1022 subjects met the inclusion criteria. The majority of the retrieved RCTs were evaluated to be of low methodological quality. The pooled results of the meta‐analysis showed that CHMs plus CMT group created better outcomes compared to CMT alone therapy, as evidenced by the fact that the overall effects of combination therapy strategy were significantly greater than the control group in increasing effective rate of cardiac function (risk ratio (RR) = 1.28; 95% CI: 1.16 to 1.42), in improving depressive symptoms (HAMD) (standard mean difference (SMD) = −1.31; 95% CI: −1.68 to −0.95) and quality of life (MLHFQ) (weighted mean difference (WMD) = −8.42; 95% CI: −10.08 to −6.76), in increasing LVEF scores (WMD = 5.33; 95% CI: 4.30 to 6.35). Conclusion. The combination of CHMs and CMT increased the effective rate of cardiac function and LVEF scores and reduced HAMD and MLHFQ scale scores, which was a potential therapeutic strategy that improved the management of CHF patients complicated with depression. Future trials were needed to verify the above results since abnormal heterogeneity and poor quality of literature have existed in the included studies.
Time-Space Fractional Model for Complex Cylindrical Ion-Acoustic Waves in Ultrarelativistic Plasmas
Authors: Liu Quansheng , Chen Liguo
Published: April 2020

In this paper, the fractional order models are used to study the propagation of ion-acoustic waves in ultrarelativistic plasmas in nonplanar geometry (cylindrical). Firstly, according to the control equations, (2 + 1)-dimensional (2D) cylindrical Kadomtsev–Petviashvili (CKP) equation and 2D cylindrical-modified Kadomtsev–Petviashvili (CMKP) equation are derived by using multiscale analysis and reduced perturbation methods. Secondly, using the semi-inverse method and the fractional variation principle, the abovementioned equations are derived the time-space fractional equations (TSF-CKP and TSF-CMKP). Furthermore, based on the fractional order transformation, the 1-decay mode solution of the TSF-CKP equation is obtained by using the simplified homogeneous balance method, and using the generalized hyperbolic-function method, the exact analytic solution of TSF-CMKP equation is obtained. Finally, the effects of the phase speedλ, electron number density (throughβ3) and the fractional orderα,β,ωon the propagation of ion-acoustic waves in ultrarelativistic plasmas are analyzed.
Expression of Tumour-Associated MUC1 Is a Poor Prognostic Marker in Breast Cancer in Kumasi, Ghana
Authors: Atta Manu E. , Bedu-Addo K. , Titiloye N. A. , Ameh-Mensah C. , Opoku F. , Duduyemi B. M.
Published: April 2020

Background. Immunohistochemical assessment of breast cancer and stratification into the basic molecular subtypes afford a much deeper insight into the biology of breast cancer, while presenting with opportunities to exploit personalized, targeted treatment. Traditionally, the oestrogen, progesterone, and epidermal growth factor receptors are assessed. MUC1, a transmembrane mucin, has been demonstrated a potential prognostic and metastatic marker in breast cancer. However, there have been a limited number of studies addressing the predictive and prognostic features of MUC1 in African breast cancer. This study aims at addressing the expression profiles of MUC1 and other biomarkers in Ghanaian breast cancer and determines its predictive and prognostic characteristics, in relation to other clinicopathological features. Methods. Haematoxylin and eosin (H&E) slides of breast cancer cases were reviewed and 203 suitable cases were selected for tissue microarray (TMA) construction and immunohistochemistry. Anti-ER, PR, HER2, Ki-67, and MUC1 antibodies were used. Results from the immunostaining were analysed using SPSS version 23. Results. About 59% of cases expressed MUC1. Majority of cases in the study showed a lack of expression of all three traditional markers (29% expressed ER, 10.9% PR, and 20.7% HER2). Ki-67 index were 62.1% (low), 16.5% (moderate), and 21.4% (high). MUC1 expressions among the molecular classes were luminal A (60.7%), luminal B (68.8%), HER2 overexpression (87.5%), and triple negative (56.6%). There were significant associations between MUC1 and HER2 overexpression (p=0.01) and triple negative (p<0.01). Conclusion. The high proportion of breast cancer cases expressing MUC1, as well as its association with the two most aggressive molecular classes, indicate a substantial role in the biology of breast cancer in our cohort, and it is an indication of poor prognosis.
Long Noncoding RNAs Control the Modulation of Immune Checkpoint Molecules in Cancer
Authors: Xu Shouping , Wang Qin , Kang Yujuan , Liu Jiena , Yin Yanling , Liu Lei , Wu Hao , Li Siwei , Sui Shiyao , Shen Meiying , Zheng Wei , Pang Da
Published: April 2020

Long noncoding RNAs (lncRNA) that are associated with immune checkpoints have not been identified, and the mechanism by which such lncRNAs might regulate the expression of immune checkpoints is unknown in human cancer. Immune checkpoint–associated lncRNAs (ICP-lncRNA) were identified and validated via a comprehensive bioinformatic analysis of The Cancer Genome Atlas data. These ICP-lncRNAs were involved in key immune response and immune cell receptor signaling pathways. The expression of ICP-lncRNAs was upregulated and correlated with a poor prognosis in patients with cancer. HLA complex P5 (HCP5) and myocardial infarction associated transcript (MIAT) promoted tumor growth and upregulated the expression of PD-L1/CD274 via a competing endogenous RNA mechanism of sponging miR-150-5p. The combination of MIAT knockdown and PD-L1 antibody administration showed a synergistic inhibitory effect on tumor growth. Finally, the expression of both HCP5 and MIAT was confirmed to be transcriptionally suppressed by CCCTC-binding factor (CTCF), and lipopolysaccharide induced CTCF eviction from the HCP5 and MIAT promoters, attenuating the transcriptionally suppressive activity of CTCF. This study enlarges the functional landscape of known lncRNAs in human cancer and indicates novel insights into their roles in the field of tumor immunity and immunotherapy. These findings may aid in the comprehensive management of human cancer with immunotherapy.
Recombinant Cellular Repressor of E1A-Stimulated Genes Protects against Renal Fibrosis in Dahl Salt-Sensitive Rats
Authors: Liu Mei-Li , Song Hai-Xu , Tian Xiao-Xiang , Liu Yan-Xia , Liu Dan , Hou Zhi-Wei , Li Jia-Yin , Yan Cheng-Hui , Han Ya-ling
Published: April 2020

Background: Human cellular repressor of E1A-stimulated genes (CREG) is a secreted glycoprotein that attenuates angiotensin II-induced hypertension, alleviates myocardial fibrosis, and improves heart function. However, the role of CREG in high-salt (HS) diet-induced hypertensive nephropathy is unclear. Methods: To determine the effects and molecular mechanisms of CREG in HS diet-induced hypertensive nephropathy, we established a hypertensive nephropathy animal model in Dahl salt-sensitive (SS) rats fed a HS diet (8% NaCl, n = 20) for 8 weeks. At week 4 of HS loading, these rats were administered recombinant CREG (reCREG; 35 µg/kg·day, n = 5) and saline (n = 5) via subcutaneously implanted pumps and were also administered the vasodilator hydralazine (20 mg/kg·day, n = 5) in drinking water. We used hematoxylin and eosin staining, Masson’s trichrome staining, immunohistochemical labeling, western blotting, RT-PCR, and Tunel staining to determine the signaling pathways of CREG in HS diet-induced hypertensive nephropathy. Results: After 8 weeks of HS intake, the Dahl SS rats developed renal dysfunction and severe renal fibrosis associated with reductions of 78 and 67% in CREG expression, respectively, at both mRNA and protein levels in the kidney. Administration of reCREG improved renal function and relieved renal fibrosis. Administration of CREG also inhibited monocyte infiltration and reduced apoptosis in the kidney cells. CREG overexpression upregulated forkhead box P1 expression and inhibited the transforming growth factor-β1 signaling pathway. Conclusion: Our study shows that CREG protected the kidney against HS-diet-induced renal damage and provides new insights into the mechanisms underlying kidney injury.
A Case of Tyrosine Kinase Inhibitor-Resistant Chronic Myeloid Leukemia, Chronic Phase with ASXL1 Mutation
Authors: Imataki Osamu , Ishida Tomoya , Kubo Hiroyuki , Uemura Makiko , Nanya Yasuhito , Kawakami Kimihiro , Ogawa Seishi , Kadowaki Norimitsu
Published: April 2020

Hematological malignancies, including chronic myeloid leukemia (CML), exhibit ASXL1 mutations; however, the function and molecular mechanism of these mutations remain unclear. ASXL1 was originally identified as tumor suppressor gene, in which loss of function causes myelodysplastic syndrome (MDS). ASXL1 mutations are common and associated with disease progression in myeloid malignancies including MDS, acute myeloid leukemia, and similarly in CML. In MDS, ASXL1 mutations have been associated with poor prognosis; however, the impact of ASXL1 mutations in CML has not been well described. A 31-year-old male was diagnosed as CML-chronic phase (CP). Laboratory findings showed a white blood cell count of 187,200/µL, with asymptomatic splenomegaly. Blast count was 5.0% in peripheral blood and 7.3% in bone marrow. There was no additional chromosomal abnormality except for t(9;22)(q34;q11.2) by chromosomal analysis. At onset, the Sokal score was 1.4, indicating high risk. The patient received tyrosine kinase inhibitor (TKI) therapy, comprising nilotinib ∼600 mg/day, bosutinib ∼600 mg/day, ponatinib ∼45 mg/day, and dasatinib ∼100 mg/day. Nevertheless, after 1.5 years of continuous TKI therapy, the best outcome was a hematological response. Although additional chromosomal aberrations and ABL1 kinase mutations were analyzed repeatedly before and during TKI therapy, known genetic abnormalities were not detected. Thereafter, the patient underwent bone marrow transplantation from an HLA 7/8 matched unrelated donor (HLA-Cw 1 locus mismatch, graft-versus-host direction). The patient achieved neutrophil engraftment, 18 days after transplantation, leading to complete remission with an undetectable level of BCR-ABL1 mRNA. The patient, however, died from graft-versus-host disease and thrombotic microangiopathy after 121 days. Gene sequence analysis of his CML cell before stem cell transplantation revealed ASXL1 mutations. Physiologically, ASXL1 contributes to epigenetic regulation. In the CML-CP patient in this case report, ASXL1 mutation conferred resistance to TKI through obscure resistance mechanisms. Even though a molecular mechanism for TKI resistance in ASXL1 mutation in CML has remained obscure, epigenetic modulation is a plausible mode of CML disease progression. The clinical impact including prognosis of ASXL1 for CML is underscored. And the treatment strategy of CML with ASXL1 mutation has not been established. A discussion of this case was expected to facilitate treatment options.
Risk Factors for Community-Acquired Acute Kidney Injury in Medical Patients: A Nested Case-Control Study
Authors: Cely Javier Enrique , Mendoza Elkin José , Sprockel John Jaime , Perez Luis Carlos , Mateus Janeth Marcela , Maldonado Sebastian , Diaztagle Juan José
Published: April 2020

Introduction: Research about the risk factors associated with community-acquired acute kidney injury (CA-AKI) in acute medical diseases is scarce. Data extrapolation from surgical to medical illnesses is questionable. Objectives: To evaluate potential risk factors and hospital outcomes associated with a CA-AKI in medical illnesses. Methods: We performed an unmatched nested case-control study from a previous prospective cohort study. We included adult patients with acute illnesses treated with internal medicine. Cases were defined as patients with a CA-AKI diagnosis upon hospital admission, and controls included patients from the same cohort who did not develop AKI during the first 5 days of hospitalisation. A logistic regression model was used to assess the association between potential risk factors and ­CA-AKI. Results: A total of 868 patients were included in the study (223 cases and 645 controls). The median age was 65 years (interquartile range 50–78). In a logistic regression model, the risk factors associated with CA-AKI included chronic kidney disease (CKD; OR 6.27; 95% CI 2.95–13.3, p < 0.001), ≥65 years old (OR 1.72; 95% CI 1.16–2.57, p = 0.007), acute bacterial infection (OR 1.95; 95% CI 1.36–2.80, p < 0.001), hypovolaemia (OR 1.88; 95% CI 1.32–2.69, p < 0.001), pre-hospital nephrotoxic drugs (OR 1.77; 95% CI 1.23–2.55, p = 0.002), anaemia (OR 1.49; 95% CI 1.03–2.14, p = 0.031) and systolic blood pressure (SBP) <107 mm Hg (OR 2.25; 95% CI 1.38–3.67, p = 0.001). A significant interaction between CKD and age was found (p = 0.017) and included in the model (patients with CKD and ≥65 years old [OR 10.85; 95% CI 4.14–28.41, p < 0.001]). The area under the receiver operating characteristic curve of the final model was 0.743. Conclusions: CKD is strongly associated with CA-AKI upon hospital admission in medical illnesses patients. Older age enhances the risk of CA-AKI in patients with CKD. Other risk factors include pre-hospital nephrotoxic drugs, acute bacterial infection, anaemia, low SBP and hypovolaemia.
Cerebral Impaludation – An Ignoble Procedure between Two Nobel Prizes: Frontal Lobe Lesions before the Introduction of Leucotomy
Authors: Blomstedt Patric
Published: April 2020

During the 20th century, only two persons have been awarded the Nobel Prize for psychiatric discoveries, Julius Wagner-Jauregg in 1927 for the introduction of malaria inoculation in dementia paralytica and Egas Moniz in 1949 for prefrontal leucotomy. According to traditional narrative, Moniz was inspired by a presentation by Carlyle Jacobsen on prefrontal lesions in chimpanzees at a congress in London in 1935. A few months later, he performed the first operations with the help of a young neurosurgeon. These leucotomies were done using injections of a small amount of alcohol into each frontal lobe through a single burr hole on each side of the skull, and the findings from the first 20 patients were published soon after that in 1936. It has, however, been difficult to reconstruct the path leading Moniz to frontal leucotomy, due to his unwillingness to acknowledge contributions from others. Maurice Ducosté, psychiatrist at Villejuif in Paris, France, started his work with psychiatric patients in the early 1920s with mechanical lesions in schizophrenia and continued with injections into the frontal lobes. Later, he focused on general paresis of the insane in neurosyphilis. Here, he introduced injections of malaria-infested blood into the frontal lobes – cerebral impaludation. Injections were used also in schizophrenia, mania, melancholia, and other psychiatric conditions. These injections were up to 5 mL in volume and could be repeated up to 12 times in an individual patient, which must have created significant lesions. Ducosté performed his procedure in hundreds of psychiatric patients before Moniz attempted leucotomy, and his work was presented in several publications before that by Moniz. Moniz basically used the same entry point, target depth, and technique in his first leucotomies. The major difference was that Moniz used alcohol with the clear intent of producing a lesion. Further, Moniz must have been aware of the work of Ducosté, since they presented papers, one after the other, at a meeting of the French Academy of Medicine in 1932. Even so, Moniz never acknowledged any contribution by Ducosté. In my opinion, it would be appropriate to acknowledge the contribution of Maurice Ducosté to the introduction of lobotomy.
Outcome of Insertable Cardiac Monitors in Symptomatic Patients with Brugada Syndrome at Low Risk of Sudden Cardiac Death
Authors: Sakhi Rafi , Assaf Amira , Theuns Dominic A.M.J. , Verhagen Judith M.A. , Szili-Torok Tamas , Roos-Hesselink Jolien W. , Yap Sing-Chien
Published: April 2020

Introduction: There is limited data on the experience with insertable cardiac monitors (ICMs) in patients with Brugada syndrome. Objective: To evaluate the outcome of ICM in symptomatic patients with Brugada syndrome who are at suspected low risk of sudden cardiac death (SCD). Methods: We conducted a prospective single-center cohort study including all symptomatic patients with Brugada syndrome who received an ICM (Reveal LINQ) between July 2014 and October 2019. The main indication for monitoring was to exclude ventricular arrhythmias as the cause of symptoms and to establish a symptom-rhythm relationship. Results: A total of 20 patients (mean age, 39 ± 12 years; 55% male) received an ICM during the study period. Nine patients (45%) had a history of syncope (presumed nonarrhythmogenic), and 5 patients had a recent syncope (<6 months). During a median follow-up of 32 months (interquartile range, 11–36 months), 3 patients (15%) experienced an episode of nonsustained ventricular arrhythmia. No patient died suddenly or experienced a sustained ventricular arrhythmia, and no patient had a recurrence of syncope. Overall, 17 patients (85%) experienced symptoms during follow-up, of whom 10 patients had an ICM-detected arrhythmia. In 4 patients (20%), the ICM-detected arrhythmia was an actionable event. ICM-guided management included antiarrhythmic drug therapy for symptomatic ectopic beats (n = 3), pulmonary vein isolation, and oral anticoagulation for atrial fibrillation (n = 1), electrophysiological study for risk stratification (n = 1), and pacemaker implantation for atrioventricular block (n = 1). Conclusions: An ICM can be used to exclude ventricular arrhythmias in symptomatic patients with Brugada syndrome at low risk of SCD. Furthermore, an ICM-detected arrhythmia changed clinical management in 20% of patients.
A Study on the Relationship between Cognitive Performance, Hearing Impairment, and Frailty in Older Adults
Authors: Bonfiglio Viviana , Umegaki Hiroyuki , Kuzuya Masafumi
Published: April 2020

Introduction: As the human lifespan rises, older people are increasingly affected by multimorbidity, including hearing impairment (HI), frailty, and cognitive decline. Objective: We studied the effect of HI on the cognitive performance of older patients with mild cognitive impairment and mild dementia and how this effect is altered when HI and frailty coexist. Methods: The sample comprised 172 outpatients (age ≥65 years) with a Clinical Dementia Rating of 0.5–1 and a Mini-Mental State Examination score ≥20. Cognitive, neuropsychological, physical function tests, and body measurements were performed. The participants’ comorbidity indices were calculated, and they were asked to report their hearing condition. Finally, the participants were divided into 4 groups based on the presence of frailty, HI, both conditions, or neither. Results: The presence of HI was significantly associated with a lower Digit Symbol Substitution Test (DSST) score (unadjusted model: p = 0.003; adjusted: p = 0.012). Moreover, people with both HI and frailty were more likely to have a low DSST score than those in the other groups (unadjusted model: OR: 3.741, 95% CI: 1.374–10.183, p = 0.010; adjusted model: OR: 4.192, 95% CI: 1.026–17.136, p = 0.046). Conclusions: This study highlights the negative relationship between cognitive performance scored on the DSST and the presence of HI. Furthermore, the presence of both frailty and HI is associated with a worse cognitive score than HI alone.
Blood Pressure and Anticoagulation Reversal Management during Off-Hours in Oral Anticoagulation-Associated Intracerebral Hemorrhage
Authors: Mrochen Anne , Sprügel Maximilian I. , Gerner Stefan T. , Sembill Jochen A. , Lang Stefan , Lücking Hannes , Kuramatsu Joji B. , Huttner Hagen B.
Published: April 2020

Background: Prevention of hematoma enlargement in oral anticoagulation-associated intracerebral hemorrhage (OAC-ICH) focuses on blood pressure (BP) reduction and OAC reversal. We investigated whether treatment efficiency and clinical outcomes differ between OAC-ICH patients admitted outside versus during regular working hours. Methods: Based on pooled data of multicenter cohort studies, we grouped OAC-ICH patients (vitamin K antagonist [VKA], non-vitamin K oral anticoagulant [NOAC]) according to on- vs. off-hour admission. Primary outcome was the functional outcome using the modified Rankin scale (mRS) dichotomized into favorable (mRS 0–3) and unfavorable (mRS 4–6) and mortality at 3 months. Secondary outcome measures included the occurrence of hematoma enlargement, the proportions of patients with systolic BP <140 mm Hg and with anticoagulation treatment achieving international normalized ratio (INR) levels <1.3 at 4 h. Propensity score matching (PSM) was performed to account for imbalances in baseline characteristics. Results: The study population consisted of 76/126 NOAC-ICH patients and 1,005/1,470 VKA patients presenting during off-hours. Functional outcome and mortality rates were not significantly different among PSM patients with VKA-ICH and NOAC-ICH during on- vs. off-hours (mRS 4–6 VKA-ICH: on-hour: 239/357 [66.9%] vs. 253/363 [69.7%] off-hour; p = 0.43; NOAC-ICH: on-hour 26/42 [61.9%] vs. off-hour: 37/57 [64.9%]; p = 0.76; mRS 6 VKA-ICH: on-hour: 127/357 [35.6%] vs. off-hour: 148/363 [40.8%]; p = 0.15; ­NOAC-ICH: on-hour 17/42 [40.5%] vs. off-hour: 16/57 [28.1%]; p = 0.20). There were no differences detectable regarding the secondary outcome measures (i.e., hematoma enlargement, the proportion of patients who achieved systolic BP levels <140 mm Hg at 4 h as well as anticoagulation treatment achieving INR levels <1.3 at 4 h) in OAC patients. Conclusion: Our study implies that BP reduction and anticoagulation reversal management are well established and associated with similar rates of hematoma enlargement and clinical outcomes in on- vs. off-hour admitted OAC-ICH patients.
Differential Secretion of Inflammatory Cytokines by Human Trophoblasts in the Presence of Escherichia coli, Lactobacillus crispatus, and Lactobacillus jensenii
Authors: Alhousseini Ali , Vadillo-Ortega Felipe , Palacios-Gonzalez Berenice , Theis Kevin R. , Winters Andrew D. , Hassan Sonia S. , Meraz-Cruz Noemi
Published: April 2020

Introduction: The existence of a placental microbiome would require a non-antagonistic relationship between potentially colonizing bacteria and trophoblasts. Objective: The immunologic response of trophoblasts to specific potentially invading bacteria needs further analysis. Methodology: Immortalized first trimester human trophoblasts Swan 71 (Sw.71) were coincubated with Escherichia coli, Lactobacillus jensenii, Lactobacillus crispatus, and incubated alone (i.e., control group; 4 conditions with n = 6 for each condition). Chemokines and cytokines were measured. ANOVA with post hoc pairwise analysis was used to compare cytokines/chemokines concentrations in the 4 culture media. Results: Sw.71 co-incubated with E. coli, L. jensenii or L. crispatus resulted in differential secretion of 11 of the 26 assayed cytokines/chemokines. Sw.71 co-incubated with any of the 3 bacteria responded with significant increased secretion of interleukin (IL)-8 and granulocyte macrophage colony-stimulating factor. All bacteria elicited the secretion of IL-6 and interferon (IFN) α2, 2 proinflammatory cytokines. In addition, Lactobacillus species resulted in increased secretion of IL-12p40 and IFNγ. While E. coli did not modify secretion of anti-inflammatory cytokines, Sw.71 cells responded to co-incubation with Lactobacillus species by secreting increased levels of IL-10 and IL-1ra. Both Lactobacillus species led to a decreased secretion of IL-4. Conclusion: All 3 bacterial species triggered significant release of chemokines and inflammatory cytokines, suggesting that a commensal relationship with trophoblasts may not be feasible.
Association Between Carotid Bifurcation Geometry and Atherosclerotic Plaque Vulnerability
Authors: Jiang Peirong , Chen Zhensen , Hippe Daniel S. , Watase Hiroko , Sun Bin , Lin Ruolan , Yang Zheting , Xue Yunjing , Zhao Xihai , Yuan Chun
Published: April 2020

Objective:

Carotid bifurcation geometry has been believed to be a risk factor for the initiation of atherosclerosis because of its influence on hemodynamics. However, the relationships between carotid bifurcation geometry and plaque vulnerability are not fully understood. This study aimed to determine the association between carotid bifurcation geometry and plaque vulnerability using magnetic resonance vessel wall imaging.

Approach and Results:

A total of 501 carotid arteries with nonstenotic atherosclerosis were included from the cross-sectional, multicenter CARE II study (Chinese Atherosclerosis Risk Evaluation). Four standardized carotid bifurcation geometric parameters (bifurcation angle, internal carotid artery planarity, luminal expansion FlareA, and tortuosity Tort2D) were derived from time-of-flight magnetic resonance angiography. Presence of vulnerable plaque, which was characterized by intraplaque hemorrhage, large lipid-rich necrotic core, or disrupted luminal surface, was determined based on multicontrast carotid magnetic resonance vessel wall images. Vulnerable plaques (N=43) were found to occur at more distal locations (ie, near the level of flow divider) than stable plaques (N=458). Multivariable logistic regression showed that the luminal expansion FlareA (odds ratio, 0.45 [95% CI, 0.25–0.81];
P
=0.008) was associated with plaque vulnerability after adjustment for age, sex, maximum wall thickness, plaque location, and other geometric parameters.

Conclusions:

Smaller luminal expansion at carotid bifurcation is associated with vulnerable plaque. The finding needs to be verified with longitudinal studies and the underlying mechanism should be further explored with hemodynamics measurement in the future.
Social Determinants of Health and 90‐Day Mortality After Hospitalization for Heart Failure in the REGARDS Study
Authors: Sterling Madeline R. , Ringel Joanna Bryan , Pinheiro Laura C. , Safford Monika M. , Levitan Emily B. , Phillips Erica , Brown Todd M. , Goyal Parag
Published: April 2020

Background

Outcomes following heart failure (
HF
) hospitalizations are poor, with 90‐day mortality rates of 15% to 20%. Although prior studies found associations between individual social determinants of health (
SDOH
) and post‐discharge mortality, less is known about how an individuals’ total burden of
SDOH
affects 90‐day mortality.

Methods and Results

We included participants of the REGARDS (
Re
asons for Geographic and Racial Differences in Stroke) Study who were Medicare beneficiaries aged ≥65 years discharged alive after an adjudicated
HF
hospitalization. Guided by the Healthy People 2020 Framework, we examined 9
SDOH
. First, we examined age‐adjusted associations between each
SDOH
and 90‐day mortality; those associated with 90‐day mortality were used to create an
SDOH
count. Next, we determined the hazard of 90‐day mortality by the
SDOH
count, adjusting for confounders. Over 10 years, 690 participants were hospitalized for
HF
at 440 unique hospitals in the United States; there were a total of 79 deaths within 90 days. Overall, 28% of participants had 0
SDOH
, 39% had 1, and 32% had ≥2. Compared with those with 0, the age‐adjusted hazard ratio for 90‐day mortality among those with 1
SDOH
was 2.89 (95% CI, 1.46–5.72) and was 3.06 (1.51–6.19) among those with ≥2
SDOH
. The adjusted hazard ratio was 2.78 (1.37–5.62) and 2.57 (1.19–5.54) for participants with 1
SDOH
and ≥2, respectively.

Conclusions

While having any of the
SDOH
studied here markedly increased risk of 90‐day mortality after an
HF
hospitalization, a greater burden of
SDOH
was not associated with significantly greater risk in our population.
The Origin of the Sogdian Civic Communities (nāf)
Authors: Shenkar Michael
Published: April 2020

The article discusses when, how and why oligarchic, self-governed civic communities (nāf) emerged in Sogdiana. On the basis of primary sources, such as the Kultobe inscriptions, and on comparative material from the two best-known city-state cultures—the Greek poleis and the medieval north Italian republics—it is argued that the development of the Sogdian civic communities occurred during the first century BCE-second century CE, when Sogdiana was part of the nomad-ruled Kangju state. This process is linked to Sogdian colonial expansion and the growth in the volume and complexity of trade.
Mantra: a Review Essay on Islam in Soviet Central Asia
Authors: Tasar Eren
Published: April 2020

This paper traces the development of the historiography of Islam in Soviet Central Asia from the Cold War’s outset to the present by illustrating its uncritical reproduction of modernist and communist templates for describing Muslim religiosity, and its debt to two foundational frames of Soviet antireligious propaganda: “survivals” and “nationalized Islam.” It highlights the important implications of these frames for this scholarship’s development, i.e., its assumptions concerning “normativity” and the “poverty” of Central Asian Islam, as well as the urban-rural divide’s salience in religious life. The essay concludes with a survey of recent scholarship on the subject.
Mohini: A Case Study of a Transnational Spiritual Space in the History of the Theosophical Society
Authors: Mukhopadhyay Mriganka
Published: April 2020

This essay investigates the well-known, yet understudied, Bengali Theosophist Mohini Mohun Chatterji. In this essay, Mohini Chatterji’s life and career will be discussed in relation to the Theosophical Society. His case will be seen as an example of how Bengali Theosophists played a significant role in the transcultural, entangled history of the global Theosophical movement, thus connecting Vedantic philosophy with occultism.
(Re)Introducing “Secular Religion”: On the Study of Entangled Quests for Meaning in Modern Western Cultures
Authors: Vliegenthart Dave
Published: April 2020

The disenchantment of reality has bankrupted conventional sources of meaning for many people in modern Western cultures. This has led a growing number of figures and groups to search for alternative sources of meaning. Typical of their quests for meaning is the entanglement of secular and religious discourses. Since the twentieth century, scholars have studied the social configurations of these figures and groups as “cults” or “new religious movements” and their ideologies as “New Age” or “spirituality,” which are seen as parts of a longer tradition of “Western esotericism” (Europe) or “metaphysical religion” (North America). Several leading scholars have also interpreted them as forms of “secular religion,” but this has yet to gain academic traction. This article argues that the former concepts are lacking or losing a logical connection with the socio-historical phenomena to which they pertain and reintroduces the latter concept as a more appropriate one.