bluuebunny/crossref_metadata_2025 huggingface dataset:
Reliability of Endoscopic Ultrasound Using Miniprobes and Grayscale Histogram Analysis in Diagnosing Upper Gastrointestinal Subepithelial Lesions
Authors: Khan Samiullah , Zhang Rui , Fang Weili , Wang Tao , Li Shu , Wang Danna , Chang Yixiang , Zhu Lanping , Wang Bang-mao , Liu Wentian
Published: June 2020

Background. To assess the role of endoscopic ultrasound (EUS) in the diagnosis of upper gastrointestinal subepithelial lesions (SELs) and to investigate EUS combined with a grayscale histogram analysis for the differentiation of leiomyomas and gastrointestinal stromal tumors (GISTs). Methods. A retrospective study of 709 patients with upper gastrointestinal SELs was conducted by EUS before endoscopic resection. The EUS findings of SELs and pathological results after endoscopic resection were compared. The EUS images of SELs, particularly, leiomyoma and GIST, were further analyzed via a grayscale histogram to differentiate between the two tumors. Results. Of the 709 patients, 47 cases were pathologically undetermined. The diagnostic consistency of EUS with endoscopic resection was 88.2% (584/662), including 185 muscularis mucosa, 61 submucosa, and 338 muscularis propria, respectively. The diagnostic consistency of EUS with pathology was 80.1% (530/662). The gray value of GISTs was significantly higher than that of leiomyomas (58.9±8.3 vs. 39.5±5.9, t=57.0, P<0.0001). The standard deviation of leiomyomas was significantly lower than that of GISTs (20.6±7.0 vs. 39.8±9.3, t=23.7, P<0.0001). The grayscale histogram analysis of GISTs showed higher echo ultrasound, and the echo of leiomyoma was more uniform. Conclusion. EUS is the preferred procedure for the evaluation of upper gastrointestinal SELs. EUS combined with a grayscale histogram analysis is an effective method for the differentiation of leiomyomas and GISTs.
Solutions of a Class of Degenerate Kinetic Equations Using Steepest Descent in Wasserstein Space
Authors: Marcos Aboubacar , Soglo Ambroise
Published: June 2020

We use the steepest descent method in an Orlicz–Wasserstein space to study the existence of solutions for a very broad class of kinetic equations, which include the Boltzmann equation, the Vlasov–Poisson equation, the porous medium equation, and the parabolic p-Laplacian equation, among others. We combine a splitting technique along with an iterative variational scheme to build a discrete solution which converges to a weak solution of our problem.
Study on the Ground Movement in an Open‐Pit Mine in the Case of Combined Surface and Underground Mining
Authors: Wang Zhenwei , Song Gaofeng , Ding Kuo
Published: June 2020

The combined surface and underground mining method is typically used in an open‐pit mine for better production and profits. However, the improved scale of mining operations at the combined mining conditions results in even more intensive strata movement and massive ground damages. This paper assesses the progressive development of the characteristics of roof movement with the longwall face advance and its influence on the ground movement at the slope area using physical models. The identification of strata zones at the combined mining conditions is also included. The results show the following: (1) the failure of the competent strong roof creates an inverse arch‐shaped rock block structure, which compacts the loose rock fragments in the caved zone; (2) a bed separation occurs above the inverse structure at the top of the disturbed strata configuration and extends upward with the face advance until it approaches the continuous bending zone; (3) more intensive strata movement and ground damages are produced by the large‐scale multiseam mining operations, while regular and more distinct strata zones in the disturbed configuration are identified for less intensive single‐seam mining; and (4) the intensive and massive underground mining activities increase the slope strata movement at the surface mining side. This research suggests that a less intensive mining activity is preferred in the combined surface and underground mining conditions from the point of view of ground control.
The Lymphatic Cell Environment Promotes Kaposi Sarcoma Development by Prox1-Enhanced Productive Lytic Replication of Kaposi Sarcoma Herpes Virus
Authors: Choi Dongwon , Park Eunkyung , Kim Kyu Eui , Jung Eunson , Seong Young Jin , Zhao Luping , Madhavan Shrimika , Daghlian George , Lee Hansuh H. , Daghlian Patill T. , Daghlian Saren , Bui Khoa , Koh Chester J. , Wong Alex K. , Cho Il-Taeg , Hong Young-Kwon
Published: June 2020

Kaposi sarcoma is the most common cancer in human immunodeficiency virus–positive individuals and is caused by Kaposi sarcoma–associated herpesvirus (KSHV). It is believed that a small number of latently infected Kaposi sarcoma tumor cells undergo spontaneous lytic reactivation to produce viral progeny for infection of new cells. Here, we use matched donor-derived human dermal blood and lymphatic endothelial cells (BEC and LEC, respectively) to show that KSHV-infected BECs progressively lose viral genome as they proliferate. In sharp contrast, KSHV-infected LECs predominantly entered lytic replication, underwent cell lysis, and released new virus. Continuous lytic cell lysis and de novo infection allowed LEC culture to remain infected for a prolonged time. Because of the strong propensity of LECs toward lytic replication, LECs maintained virus as a population, despite the death of individual host cells from lytic lysis. The master regulator of lymphatic development, Prox1, bound the promoter of the RTA gene to upregulate its expression and physically interacted with RTA protein to coregulate lytic genes. Thus, LECs may serve as a proficient viral reservoir that provides viral progeny for continuous de novo infection of tumor origin cells, and potentially BECs and mesenchymal stem cells, which give rise to Kaposi sarcoma tumors. Our study reveals drastically different host cell behaviors between BEC and LEC and defines the underlying mechanisms of the lymphatic cell environment supporting persistent infection in Kaposi sarcoma tumors.

Significance:

This study defines the mechanism by which Kaposi's sarcoma could be maintained by virus constantly produced by lymphatic cells in HIV-positive individuals.
TCR Repertoire Changes during TIL Expansion: Clonal Selection or Drifting?
Authors: Lozano-Rabella Maria , Gros Alena
Published: June 2020

T-cell receptor β analysis can be exploited to monitor changes in the clonotypic composition of tumor-infiltrating lymphocyte (TIL) during ex vivo expansion in IL2. Oligoclonal TILs are often outgrown by infrequent clonotypes with greater proliferative capacity, and this could impact the antitumor reactivity of the expanded TILs.

See related article by Poschke et al., p. 4289
Endogenous Retrovirus Transcript Levels Are Associated with Immunogenic Signatures in Multiple Metastatic Cancer Types
Authors: Topham James T. , Titmuss Emma , Pleasance Erin D. , Williamson Laura M. , Karasinska Joanna M. , Culibrk Luka , Lee Michael K.C. , Mendis Shehara , Denroche Robert E. , Jang Gun-Ho , Kalloger Steve E. , Wong Hui-Li , Moore Richard A. , Mungall Andrew J. , O'Kane Grainne M. , Knox Jennifer J. , Gallinger Steven , Loree Jonathan M. , Mager Dixie L. , Laskin Janessa , Marra Marco A. , Jones Steven J.M. , Schaeffer David F. , Renouf Daniel J.
Published: June 2020

Next-generation sequencing of solid tumors has revealed variable signatures of immunogenicity across tumors, but underlying molecular characteristics driving such variation are not fully understood. Although expression of endogenous retrovirus (ERV)-containing transcripts can provide a source of tumor-specific neoantigen in some cancer models, associations between ERV levels and immunogenicity across different types of metastatic cancer are not well established. We performed bioinformatics analysis of genomic, transcriptomic, and clinical data across an integrated cohort of 199 patients with metastatic breast, colorectal, and pancreatic ductal adenocarcinoma tumors. Within each cancer type, we identified a subgroup of viral mimicry tumors in which increased ERV levels were coupled with transcriptional signatures of autonomous antiviral response and immunogenicity. In addition, viral mimicry colorectal and pancreatic tumors showed increased expression of DNA demethylation gene TET2. Taken together, these data demonstrate the existence of an ERV-associated viral mimicry phenotype across three distinct metastatic cancer types, while indicating links between ERV abundance, epigenetic dysregulation, and immunogenicity.
Sequence Evolution, Abundance, and Chromosomal Distribution of Ty1-copia Retrotransposons in the Saccharum spontaneum Genome
Authors: Yang Shan , Zeng Kai , Chen Ke , Zhao Xinwang , Wu Jiayun , Huang Yongji , Zhang Muqing , Deng Zuhu
Published: June 2020

Saccharum spontaneum is a wild germplasm resource of the genus Saccharum that has many valuable traits. Ty1-copia retrotransposons constitute a large proportion of plant genomes and affect genome sequence organization and evolution. This study aims to analyze the sequence heterogeneity, phylogenetic diversity, copy number, and chromosomal dispersion patterns of Ty1-copia retrotransposons in S. spontaneum. A total of 44 Ty1-copia reverse transcriptase subclones isolated from S. spontaneum showed a range of heterogeneity, and all sequences were A-T rich, averaging approximately 54.59%. Phylogenetic analysis divided the 44 reverse transcriptase sequences into 5 distinct lineages (Retrofit/Ale, Sire/Maximus, Bianca, Tork/TAR, and Ty1-copia like). Dot-blot hybridization revealed that Ty1-copia retrotransposons consisted of a significant component of approximately 38,900 copies and 16,300 copies per genome in the accessions YN82-114 (2n = 10x = 80) and AP85-441 (2n = 4x = 32), respectively. The results of a local blast analysis showed that there are 15,069 Ty1-copia retrotransposon copies in the genome of AP85-441, of which the Retrofit/Ale lineage had the highest copy number, followed by the Tork/TAR, Sire/Maximus, and Bianca lineages. Furthermore, both FISH and the local blast analysis with AP85-441 genomic data demonstrated that the Ty1-copia retrotransposons were unevenly distributed throughout the chromosomes. Taken together, this study provides insights into the role of Ty1-copia retrotransposons in the evolution and organization of the S. spontaneum genome.
Sensitization to Furry Animals and Clinical Relevance of House Dust Mite-Induced Allergic Rhinitis in Guangzhou, China
Authors: Chen Hao , Huang Zhifeng , Luo Wenting , Li Wanjia , Zheng Peiyan , Hu Haisheng , Sun Baoqing
Published: June 2020

Introduction: The impact of furry animal allergens on house dust mite (HDM)-induced allergic rhinitis (AR) is unclear. Objective: We aimed to investigate the co-sensitization and cross-sensitization of furry animal allergens and assess their clinical relevance with HDM-induced AR. Methods: We enrolled 268 patients with HDM-induced AR who were diagnosed with skin prick tests positive for dogs and/or cats. Specific immunoglobulin E (sIgE) for dogs (e1) and cats (e2), their components (Can f 1–5 and Fel d 1–2), and other uncommon furry animal extracts were measured. Symptoms and quality of life were assessed with a visual analog scale (VAS). Results: The VAS scores for the AR and asthma (AS; n = 166), moderate-to-severe persistent-AR (n = 132), and e1P (positive)-e2P (n = 89) groups were higher than those for single AR (n = 102), other AR classifications, and other AR sensitization profiles, respectively. The IgE positivity rates for components such as Can f 1–3 and Fel d 2 and those for rats, sheep, mice, cows, and horses were highest in e1P-e2P patients. Can f 1–4, Fel d 1, Fel d 2, or the combined allergens were positively correlated with VAS scores. AR combined with AS and sensitization to Can f 4, Fel d 1, or mice were risk factors for HDM-induced AR with VAS scores ≥5. Conclusions: Extensive cross-sensitization or co-sensitization was found between Can f 1–3, Fel d 2, or rat, sheep, mouse, cow, and horse extracts. Higher sIgE levels for Can f 1–4 and Fel d 1–2 or a higher number of furry animal allergens lead to more severe symptoms and a reduced quality of life. Combined with AS, sensitization to Can f 4, Fel d 1, or mice were risk factors for moderate-to-severe HDM-induced AR.
Temporary Right Middle Lobe Occlusion with a Blocking Device to Enable Collateral Ventilation Measurement of the Right Major Fissure
Authors: Welling Jorrit B.A. , Koster T. David , Hartman Jorine E. , van Dijk Marlies , Kerstjens Huib A.M. , Klooster Karin , Slebos Dirk-Jan
Published: June 2020

Background: Absence of interlobar collateral ventilation is essential to achieve lobar volume reduction after endobronchial valve (EBV) treatment and can be assessed using the Chartis measurement. However, especially in lower lobe measurements, Chartis can be complicated by the “no-flow phenomenon”, during which a sudden cessation of flow is observed, leading to an unreliable measurement. If this phenomenon occurs in the right lower lobe, when measuring collateral flow over the right major fissure, the entrance to the right middle lobe should be occluded, and the Chartis balloon should be placed in the right upper lobe. Both Watanabe spigots and balloon catheters can be used to achieve occlusion. Objective: Our aim was to demonstrate that right middle lobe occlusion with a blocking device is helpful in obtaining a reliable Chartis outcome in case of the no-flow phenomenon in the right lower lobe. Methods: We performed a retrospective analysis of patients scheduled for EBV treatment in an EBV registry between September 2016 and September 2019. Results: We included 15 patients with severe emphysema (median age 63 years [range 47–73], 73% female, and FEV1 24% [range 19–36] of predicted), who required temporary middle lobe occlusion (12 Watanabe spigot, 3 balloon catheter). After occlusion, a reliable Chartis outcome was obtained in all patients. Conclusion: Temporary middle lobe occlusion using a blocking device is helpful in obtaining a reliable Chartis outcome in case of a right lower lobe no-flow phenomenon.
Repetitive Transcranial Magnetic Stimulation for Dysesthesia Caused by Subacute Myelo-Optico-Neuropathy: A Case Report
Authors: Mano Tomoo , Kuru Satoshi
Published: June 2020

Subacute myelo-optico-neuropathy (SMON) is caused by the ingestion of clioquinol (5-chloro-7-iodo-8-hydroxyquinoline), which is an intestinal antibacterial drug. Patients with SMON typically suffer from abnormal dysesthesia in the lower limbs, which cannot explain the mechanism only in pathology and electrophysiology. Neuromodulation therapies are increasingly being investigated as a means of alleviating abnormal sensory disturbances. We report here the response to repetitive transcranial magnetic stimulation (rTMS) for dysesthesia in a patient with SMON. The patient underwent rTMS treatment once per week for 12 weeks. rTMS was administered at 10 Hz, 90% of the resting motor threshold over the bilateral primary motor cortex foot area, for a total of 1,500 stimuli per day. After the treatment had finished at 12 weeks, the abnormal dysesthesia gradually declined. At first, there were improvements only in the area with a feeling of adherence. Later, this sensation was eliminated. Three months following the application, most of the feeling of adherence had disappeared and the feeling of tightness was slightly reduced. In contrast, the throbbing feeling had not changed during this period. Dysesthesia may indicate a process of central sensitization, which would contribute to chronic neuromuscular dysfunction. This case suggests that rTMS is a promising therapeutic application for dysesthesia.
Primary Adrenal Insufficiency during Immune Checkpoint Inhibitor Treatment: Case Reports and Review of the Literature
Authors: Salinas Carlos , Renner Alex , Rojas Carlos , Samtani Suraj , Burotto Mauricio
Published: June 2020

As the indications and clinical use of immune checkpoint inhibitors increase, it is expected that we will face some of their less frequently reported complications. Primary adrenal insufficiency is one of them, and given its unspecific symptoms and potentially serious consequences, it is important to have a high degree of clinical suspicion. We present 3 cases and a review of the literature concerning its main clinical characteristics, diagnostics, and management.
Contemporary Outcomes of Patients with Isolated Bilateral Renal Agenesis with and without Fetal Intervention
Authors: Riddle Stefanie , Habli Mounira , Tabbah Sammy , Lim Foong Yen , Minges Melissa , Kingma Paul , Polzin William
Published: June 2020

Introduction: Bilateral renal agenesis (BRA) is a lethal diagnosis, specifically meaning that natural survival beyond birth is not expected secondary to pulmonary hypoplasia. Limited contemporary data are available about intervention and the impact of restoring amniotic fluid volume in relation to the risk for lethal pulmonary hypoplasia and other factors that might influence survival in cases of fetal BRA. Objective: We report the largest series of patients undergoing fetal intervention and postnatal care for BRA at a single comprehensive fetal center. Methods: All patients with fetal BRA were reviewed from January 2004 to November 2017. Maternal and neonatal data were collected in an institutional review board-approved retrospective review. Results: From 2014 to 2017, 20 singleton pregnancies with isolated fetal BRA were evaluated and 14 had amnioinfusion. Eight had serial infusions. Of those, there were 6 neonatal deaths. There were 2 neonatal survivors beyond 30 days; however, both died of sepsis on dialysis. One of these survivors received amnioinfusions by percutaneous approach and one via amnioport. There were no survivors to transplantation. Conclusion: Fetal intervention via amnioinfusion may promote pulmonary survivorship after birth, but postnatal survival remains poor. Future studies must place an emphasis on standardizing the postnatal approach to this patient population.
AML: Patient-Arzt Diskrepanzen in der Einschätzung von Heilungschancen
Authors: Neuendorff Nina Rosa
Published: June 2020

Background: Older patients (≥60 years) with acute myeloid leukemia (AML) face difficult decisions regarding treatment with «intensive» chemotherapy that carries significant toxicity for a small chance of a cure versus «nonintensive» chemotherapy to control the disease, but with fewer side effects. However, studies of how these patients understand the risks and benefits of such treatments are lacking. Methods: We conducted a longitudinal study of older patients newly diagnosed with AML assessing patientsʼ (n=100) and oncologistsʼ (n=11) perceptions of treatment-related mortality at enrollment and prognosis at 1 month. We examined concordance between patientsʼ and oncologistsʼ perceptions using Cohenʼs kappa (κ<0.10 indicates little/no concordance). Results: We enrolled patients within 72 hours of initiating intensive (n=50) or nonintensive (n=50) chemotherapy. Whereas 91% of patients reported that they were «somewhat» to «extremely likely» to die from treatment, oncologists estimated that only 12% were at high risk of dying because of treatment (κ=-0.09). Ninety percent of patients reported that they were «somewhat» or «very likely» to be cured of their AML, whereas oncologists estimated this chance of cure for only 31% of patients (κ=0.05). Among patients receiving intensive chemotherapy, 98% reported that they were «somewhat» or «very likely» to be cured, whereas their oncologists estimated this likelihood of cure for only 49% (κ=0.04); among those receiving nonintensive chemotherapy and their clinicians, these proportions were 82% and 13%, respectively (κ=0.03). Patients who indicated a lower likelihood of cure reported significantly higher depression symptoms (p=0.03). Conclusion: Older patients with AML overestimate the risks and benefits of treatment. Interventions to facilitate communication and enhance patientsʼ understanding of the goals of therapy and treatment risk are needed. Implications for practice: Older patients with acute myeloid leukemia (AML) are confronted with challenging decisions regarding treatment with «intensive» chemotherapy that carries significant toxicity for a small chance of a cure versus «nonintensive» chemotherapy to control the disease, but with fewer side effects. A clear understanding of the likely outcome and risks of the various treatment strategies is essential for these patients to make informed decisions about their care. This article reports that older patients with AML overestimate both the risks and benefits of treatment and have substantial misperceptions about their prognosis. Interventions to enhance patientsʼ understanding of their prognosis and treatment risk are needed.
Red Blood Cell Distribution Width and Neutrophil-to-Lymphocyte Ratio in Predicting Adverse Outcomes of Acute Kidney Injury in Hospitalized Patients
Authors: Zhu Jiefu , Zeng Cong , Zhang Lei , Shu Shaoqun , Liu Yinghong , Chen Guochun , Liu Hong , Liu Yu , Dong Zheng
Published: June 2020

Background: Acute kidney injury (AKI) is a common clinical condition with high morbidity and mortality. Early risk stratification by identifying patients at risk for death or dialysis requirement has important therapeutic implications for timely interventions. Objective: The aim of this study was to examine the association of routine blood test parameters, specifically red blood cell distribution width (RDW) and neutrophil-to-lymphocyte ratio (NLR), with the AKI patient outcomes. Methods: All adult patients hospitalized from January 1, 2016, to June 30, 2016, in the Second Xiangya Hospital of Central South University were surveyed. Demographic characteristics, laboratory measurements, comorbidities, and outcomes of a total of 1,188 adult AKI patients were analyzed. Results: The incidence of AKI was 1.8% (1,188/65,329). The all-cause mortality was 16.0% (190/1,188). The multivariable relative risk of AKI mortality comparing high RDW with low RDW was 1.84 and the risk comparing high NLR with low NLR was 2.54. RDW and NLR combination showed additive values in stratifying high-risk patients, and the predictive power was comparable to the use of serum creatinine for staging AKI. In subgroup analyses, high RDW predicted prerenal AKI mortality better than intrinsic AKI. High RDW and NLR also independently predicted renal replacement therapy (RRT) requirement in AKI patients. In contrast, WBC count and platelet-to-lymphocyte ratio did not show obvious correlations with death and RRT requirement in AKI patients. Conclusion: The results support the potential usefulness of RDW and NLR in risk stratification of AKI patients, providing additional prognostic information for treatment and supportive care.
Neurocognition in Bipolar and Depressive Schizoaffective Disorder: A Comparison with Schizophrenia
Authors: Mondragón-Maya Alejandra , Flores-Medina Yvonne , Silva-Pereyra Juan , Ramos-Mastache Daniela , Yáñez-Téllez Guillermina , Escamilla-Orozco Raúl , Saracco-Álvarez Ricardo
Published: June 2020

Introduction: Schizoaffective disorder (SA) is classified into bipolar (bSA) and depressive (dSA) subtypes. Although clinical differences between both have been reported, there is no clear information regarding their specific cognitive profile. Objective: To compare neurocognition between SA subtypes and schizophrenia (SC). Methods: A total of 61 patients were assessed and divided into 3 groups: 35 SC, 16 bSA, and 10 dSA. All participants signed an informed consent letter. The MATRICS Consensus Cognitive Battery, Central and South American version was used to assess neurocognition. The study was performed at the Instituto Nacional de Psiquiatría “Ramón de la Fuente”. Participants were identified by specialized psychiatrists. Trained neuropsychologists carried out the clinical and cognitive assessment, which lasted 2 h approximately. Results: The cognitive assessment showed a significant difference in Trail Making Test part A subtest (F[2,58] = 4.043; p = 0.023]. Post hoc analyses indicated that dSA obtained a significantly higher score than SC (MD = –11.523; p = 0.018). The f test showed a large effect size (f = 0.401). No statistical differences were observed regarding other cognitive variables. Conclusions: The cognitive profile of SA subtypes and SC is similar since no differences were found in most subtests. However, dSA may be less impaired than SC in measures of processing speed. Further research with larger samples must be conducted.
The Influence of Academic Hospitalists on Labor and Delivery Outcomes
Authors: Corey Joseph , Cuartas Karen , Leidlein Christopher , Pineles Beth , Wagner Stephen
Published: June 2020

Background: Our goal was to examine differences in maternal and neonatal outcomes following the transition from a private practice to an academic model at a community hospital. Methods: This is a retrospective cohort study of a high-volume community hospital labor and delivery unit. A private practice hospitalist group was replaced with academic hospitalists. Maternal and neonatal outcomes for patients cared for by these groups were compared. The primary outcome was a composite of maternal morbidity that included blood transfusion, anal sphincter injuries, dilation and curettage, hysterectomy, chorioamnionitis, endometritis, wound infection, intensive care unit admission, and readmission. The secondary outcomes were cesarean delivery rate and a composite of neonatal morbidity that included Apgar score ≤3 at 5 min, shoulder dystocia, birth trauma, seizure, sepsis, necrotizing enterocolitis, intraventricular hemorrhage, or mechanical ventilation. Results: 245 patients were delivered by private physicians and 447 by academic physicians over the study period. No difference in the composite maternal morbidity between private and academic hospitalist groups was identified (21 vs. 25%; aOR 1.37, 95% CI: 0.36–5.21). The academic hospitalist group had a higher cesarean delivery rate compared to the private group (25 vs. 18%; aOR 2.03, 95% CI: 1.17–3.53). There was no difference in a composite neonatal morbidity (9 vs. 8%; aOR 0.92, 95% CI: 0.052–1.63). Conclusion: Women cared for by academic hospitalists were more likely to have a cesarean delivery, but there was no difference in maternal or neonatal morbidity in patients delivered by private or academic hospitalists.
CML: Hoffnung für TKI intolerante oder resistente Patienten
Authors: Saußele Susanne
Published: June 2020

Phase-I-Studie zu ABL001 bei Patienten mit CML oder Ph+ALL Die erstmals am Menschen durchgeführte Studie mit ABL001 ist eine Dosis-Eskalations-Studie. Es soll primär die maximal verträgliche Dosis (MTD) und/oder die empfohlene Dosis für die Expansion (RDE) des Einzelwirkstoffs ABL001 bei CML- oder Ph+ALL-Patienten und in Kombination mit entweder Nilotinib oder Imatinib oder Dasatinib bei Ph-positiven CML-Patienten abgeschätzt werden. Die Sicherheit, Verträglichkeit und das pharmakokinetische (PK) Profil von ABL001 und ABL001+Nilotinib, ABL001+Imatinib und ABL001+Dasatinib werden ebenso bewertet wie die pharmakodynamischen (PD) Veränderungen in peripheren mononukleären Blutzellen (PBMC) und Knochenmarkaspirationen. Aufgrund ihres ausgeprägten pharmakologischen Profils und durch präklinische pharmakologische Studien, die eine additive Wirkung nachweisen, hat die Kombination von ABL001 und einem Tyrosinkinase-Inhibitor (TKI) das Potenzial, bei einem höheren Anteil von CML-Patienten eine tiefere molekulare Reaktion zu erzielen als eine alleinige TKI Therapie. Die Kombination hat den zusätzlichen Vorteil, dass sie auf die ABL-Kinase-Domäne an 2 verschiedenen Stellen abzielt und theoretisch eine mit einer Einzelpunktmutation verbundene Therapieresistenz verhindert. Es wird vermutet, dass eine Kombination aus Nilotinib+ABL001, Imatinib+ABL001 und/oder Dasatinib+ABL001 den Prozentsatz der Patienten erhöht, die eine vollständige molekulare Remission (CMR) erzielen, und die Zeit bis zur CMR verkürzt. Dadurch erhöht sich die Möglichkeit, bei diesen Patienten anhaltende behandlungsfreie Remissionen zu erzielen. Darüber hinaus können einige Patienten eine Unverträglichkeit gegenüber der Therapie mit TKI aufweisen oder Mutationen entwickeln, die eine Resistenz gegen die TKI-Therapie fördern. Bei diesen Patienten könnte ABL001 eine neue therapeutische Option darstellen. Die von Novartis Pharmaceuticals gesponsorte Studie startete im April 2014. Abschluss der Studie wird im März 2024 erwartet. Quelle: https://clinicaltrials.gov/ct2/show/NCT02081378 
Transurethrale Resektion des Blasentumors: Nephrostomie oder DJ-Harnleiterschiene?
Authors: Kübler Hubert
Published: June 2020

Background: Whether or not double J (DJ) stenting during transurethral resection of a bladder tumour (TURBT) harms patients with regard to possible metachronous upper urinary tract urothelial cancer (UUTUC) development remains controversial. This study evaluated the impact of DJ compared to nephrostomy placement during TURBT for bladder cancer (BCa) on the incidence of metachronous UUTUCs. Methods: We retrospectively analysed 637 patients who underwent TURBT in our department between 2008 and 2016. BCa, UUTUC and urinary drainage data (retrograde/anterograde DJ and percutaneous nephrostomy) were assessed, along with the prevalence of hydronephrosis, and mortality. Chi-square and Fisher's exact test was performed for univariate analyses. Survival analysis was performed by the Kaplan-Meier method and log-rank tests.< Results: UUTUC was noted in 28 out of 637 patients (4.4%), whereas only eight (1.3%) developed it metachronously to BCa. Out of these, four patients received DJ stents, while four patients received no urinary drainage of the upper urinary tract. Placement of urinary drainage significantly correlated with UUTUC (50.0% vs. 17.9%; p = 0.041). DJ stenting significantly correlated with UUTUC (50.0% vs. 11%; p <  0.01), while no patient with a nephrostomy tube developed UUTUC. UUTUC-free survival rates were significantly lower for patients with DJ stents than for all other patients (p = 0.001). Patients with or without DJ stents had similar overall survival (OS) rates (p = 0.73), whereas patients with nephrostomy tubes had significantly lower OS rates than all other patients (p <  0.001). Conclusions: Patients with DJ stenting during TURBT for BCa might have an increased risk of developing metachronous UUTUC. This study indicated advantages in placing nephrostomy tubes rather than DJ stents; however, confirmation requires investigation of a larger cohort. Even so, the increased mortality rate in the nephrostomy group reflected hydronephrosis as an unfavourable prognostic factor.
Distal 3p Duplication and 22q13.3 Deletion with Severe Hypotonia Originating from a Paternal Balanced Translocation (3;22)
Authors: Yalcintepe Sinem , Atli Emine I. , Atli Engin , Demir Selma , Ciftdemir Nukhet A. , Duran Ridvan , Ozdemir Janset , Gurkan Hakan
Published: June 2020

In this study, we present a case with distal 3p duplication and 22q13.3 deletion due to unbalanced meiotic segregation in her father carrying a balanced translocation. The 2-month-old girl was examined for her severe hypotonia, developmental delay, and mild dysmorphic appearance. Clinical features include broad forehead, hypertelorism, laterally extended eyebrows, long eyelashes, a depressed nasal root, bifid nasal tip, long philtrum, thin lips, posteriorly rotated ears, short neck, partial syndactyly of the right hand (fingers 3, 4) , and partial syndactyly of the right foot (toes 2, 3). After examination, the final karyotype was reported as: 46,XX,der(22)del(22)(qter)dup(3)(p22pter), and the array-CGH results showed arr[GRCh37] 3p26.3p22.1(93949_41518607)×3 and arr[GRCh37] 22q13.31q13.33(44554083_51224252)×1. The mother has a 46,XX karyotype, and her father carries a balanced translocation, 46,XY,t(3;22)(p26.3;q13.3). This is the first case with a distal 3p duplication and 22q13.3 deletion with severe hypotonia and developmental delay.
Diabetic Neuropathy: Distribution Pattern Revisited
Authors: Takahashi Osamu , Sakakibara Ryuji , Tateno Fuyuki , Aiba Yosuke
Published: June 2020

It is not well known which of the common neuropathic distribution patterns in diabetes might suggest underlying mechanisms. To examine this question, we present data from a nerve conduction study (NCS). Irrespective of symptoms, we enrolled 323 type 2 diabetic patients (206 men, 117 women; mean age 64.1 years [51–79]; duration 12.0 years [5–19]; HbA1C 8.7% [5.1–12.1]; half [n = 142] untreated). NCS was performed for the following patterns: mononeuropathy (unilateral [MNU], bilateral [MNB]), multiple mononeuropathy (MMN), and polyneuropathy (PN). In 266 patients, we performed atherosclerosis tests: cardio-ankle vascular stiffness index (CAVI) and carotid ultrasonography. Neuropathy was observed in 235, and in 88 it was not observed; the latter then served as the control group. The most common pattern was MMN (26%), followed by MNB (18%), PN (16%), and MNU (12%). A combination of demyelination and axonal damage was revealed. Longer duration of diabetes compared with controls (8.6 years) was associated with MNB (12.5 years), MMN (14.8 years), and PN (17.4 years) (p < 0.05). HbA1C was associated with PN (p < 0.05). Atherosclerosis risks were associated with MNB, MMN, and PN (p < 0.05). Our study results indicated that (multiple) mononeuropathy is the most common distribution pattern in diabetes.
The Crucial Role of Nurses and Social Workers in Initiating End-of-Life Communication to Reduce Overtreatment in the Midst of the COVID-19 Pandemic
Authors: Raftery Chris , Lewis Ebony , Cardona Magnolia
Published: June 2020

The large scale and rapid spread of the current COVID-19 pandemic has changed the way hospitals and other health services operate. Opportunities for patient-centered decision-making at the end of life are being jeopardized by a scarcity of health system resources. In response, the traditional doctor-initiated advanced care planning (ACP) for critical illness may also need to be readjusted. We propose nurse-led and allied health-led ACP discussions to ensure patient and family inclusion and understanding of the disease prognosis, prevention of overtreatment, and potential outcomes in crisis times. We highlight known barriers and list enablers, long-term and short-term opportunities to assist in the culture change.
Calcitonin Gene-Related Peptide-Induced Phosphorylation of STAT3 in Arcuate Neurons Is a Link in the Metabolic Benefits of Portal Glucose
Authors: Soty Maud , Vily-Petit Justine , Castellanos-Jankiewicz Ashley , Guzman-Quevedo Omar , Raffin Margaux , Clark Samantha , Silva Marine , Gautier-Stein Amandine , Cota Daniela , Mithieux Gilles
Published: June 2020

Introduction: Intestinal gluconeogenesis (IGN) exerts metabolic benefits in energy homeostasis via the neural sensing of portal glucose. Objective: The aim of this work was to determine central mechanisms involved in the effects of IGN on the control of energy homeostasis. Methods: We investigated the effects of glucose infusion into the portal vein, at a rate that mimics IGN, in conscious wild-type, leptin-deficient Ob/Ob and calcitonin gene-related peptide (CGRP)-deficient mice. Results: We report that portal glucose infusion decreases food intake and plasma glucose and induces in the hypothalamic arcuate nucleus (ARC) the phosphorylation of STAT3, the classic intracellular messenger of leptin signaling. This notably takes place in POMC-expressing neurons. STAT3 phosphorylation does not require leptin, since portal glucose effects are observed in leptin-deficient Ob/Ob mice. We hypothesized that the portal glucose effects could require CGRP, a neuromediator previously suggested to suppress hunger. In line with this hypothesis, neither the metabolic benefits nor the phosphorylation of STAT3 in the ARC take place upon portal glucose infusion in CGRP-deficient mice. Moreover, intracerebroventricular injection of CGRP activates hypothalamic phosphorylation of STAT3 in mice, and CGRP does the same in hypothalamic cells. Finally, no metabolic benefit of dietary fibers (known to depend on the induction of IGN), takes place in CGRP-deficient mice. Conclusions: CGRP-induced phosphorylation of STAT3 in the ARC is part of the neural chain determining the hunger-modulating and glucose-lowering effects of IGN/portal glucose.
Type specimens of true bugs (Hemiptera: Heteroptera) housed in the Museu de Zoologia da Universidade de São Paulo, Brazil
Authors: Carrenho Renan , Rodrigues Higor D.D. , Lima Adriana Carneiro de , Schwertner Cristiano Feldens
Published: June 2020

This paper provides a record of the type specimens of Heteroptera (Insecta: Hemiptera) housed in the Museu de Zoologia da Universidade de São Paulo, Brazil (MZUSP), with information on 65 primary types and 316 secondary types. These type specimens represent 116 nominal species, currently classified in five infraorders and 14 families. The taxa are presented alphabetically, followed by bibliographic citation, type status, preservation method, collection data, and taxonomic remarks when appropriate.
Food habits of the Cougar Puma concolor (Carnivora: Felidae) in the Central Andes of the Colombian Coffee Region
Authors: Muñoz Castillo Diana Camila , Perry Arbeláez Pauline , Arias-Monsalve Héctor Fabio , Ramírez-Chaves Héctor E.
Published: June 2020

The feeding habits of the cougar have been scarcely studied in Colombia, despite its importance in the ecosystems it inhabits. In this study, we analysed the diet of the cougar using 53 feces samples collected from several sites in the Central Andes of Colombia’s Coffee Growing Region. To identify prey species, we examined and compared bone fragments and hairs found in each sample with descriptions published in relevant literature and with specimens from the Natural History Museum of the Universidad de Caldas, Colombia. We found that rabbits (Sylvilagus sp.) provided half of the relative biomass consumed by the cougar (50%). Other preys identified belong to representatives of medium and large mammals such as marsupials (Didelphis: 10%), sloths (Choloepus: 9%), rodents (Coendou: 10%, Cuniculus: 9%), and deer (Mazama: 9%). Of the preys, Coendou rufescens has not, to our knowledge, been previously included in cougar diet literature. The curve of accumulation of species indicated that the number of samples obtained in this work fully describe the diet of this feline. Neither domestic species were recorded in this work, nor were there any relationships between the dry or rainy seasons and the consumption of prey species. The comparison of the information reported in this study and others carried out in the Andes may indicate the general nature of this feline’s diet and its adaptability to the prey species found in each area, since these vary in each one of them. It is probable that the obtained trophic niche value (0.33) is due to the abundance of rabbits present in the study area. It is also probable that the cougar has not consumed domestic species since, although it is close to cattle ranches, it has enough of wild prey in the area to supply its needs. The results of this study may help to improve our understanding of the feeding habits of this predator and its interaction with other species in this important region of Colombia. This will, in turn, promote major comprehension of the role of cougars in the Colombian Cordilleras and lead actions for their conservation.
Ser ou não ser sustentável, eis a questão! Um olhar sobre a relação da pesquisa em turismo e a panaceia do sustentável
Authors: Corbari Sandra Dalila , Ferreira Marina Rossi
Published: June 2020

A busca pelo crescimento econômico, mascarado por um ideal de desenvolvimento, acarretou em diversos problemas, principalmente no âmbito ambiental. O alerta sobre a má utilização dos recursos e a impossibilidade de um crescimento perpétuo culminou na busca por alternativas dentro do modelo vigente, como é o caso da noção de desenvolvimento sustentável, amplamente utilizada em várias esferas, incluindo a acadêmica e a governamental. No turismo, várias pesquisas são publicadas anualmente, utilizando-se da ideia de sustentabilidade, desenvolvimento sustentável no turismo e do turismo sustentável. No entanto, o termo “desenvolvimento sustentável” foi - e continua sendo - utilizado em diversos casos de forma indiscriminada e sem a devida reflexão sobre seu significado e viabilidade. Destarte, o presente ensaio teórico buscou delinear questões para reflexão a respeito da forma como o campo do turismo tem se apropriado de termos e ideias que, por vezes, são inviáveis e, por outras, são contraditórias. Ademais, em alguns casos, nota-se que o turismo tem se isentado do debate a respeito e de sua responsabilidade por ações que podem ser consideradas contrárias aos ideais da sustentabilidade.
Association of Omnivorous and Vegetarian Diets With Antioxidant Defense Mechanisms in Men
Authors: Cinegaglia Naiara , Acosta‐Navarro Julio , Rainho Claudia , Antoniazzi Luiza , Mattioli Sarah , Pimentel Caroline , Santos Raul D. , Sandrim Valeria
Published: June 2020

Background

Evidence that a vegetarian diet rich in antioxidants contributes to cardiovascular health are growing, however, the underlying molecular mechanisms remain unknown. HO‐1 (heme‐oxygenase‐1), a marker of adaptive response, is protective against oxidative stress and has shown cardioprotective effects. Therefore, we evaluated circulating
HO
‐1 levels and the effect of plasma from omnivorous and vegetarians in endothelial cells (human umbilical vein endothelial cells) on modulating
NRF2 (nuclear factor erythroid 2‐like 2)/HO
‐1 and nitric oxide production.

Methods and Results

From 745 participants initially recruited, 44 omnivorous and 44 vegetarian men matched by age and absence of cardiovascular risk factors and diseases were included in this study. Circulating
HO
‐1 was measured using
ELISA
and human umbilical vein endothelial cells were incubated with plasma from omnivorous and vegetarians. Higher circulating
HO
‐1 concentrations were found in omnivorous compared with vegetarians. Plasma from omnivorous and not from vegetarians induced
NRF
2/
HO
‐1 and nitric oxide production in human umbilical vein endothelial cells, and increased reactive oxygen species production and caspase activity after incubation with stressor stimulus.

Conclusions

We suggest that
HO
‐1 induction in omnivorous may indicate a pro‐oxidative status since
HO
‐1 is activated under oxidative stress a state not seen in vegetarians.
Differential Impact of Aging on Cardiovascular Risk in Women Military Service Members
Authors: Chen Xiaofei , Ramanan Bala , Tsai Shirling , Jeon‐Slaughter Haekyung
Published: June 2020

Background

Atherosclerotic cardiovascular disease (
ASCVD
) is the third leading cause of death in women service members and veterans. This study assessed 10‐year
ASCVD
risk in women service members and veterans using their own electronic health record data extracted from Veterans Affairs (
VA
) national Corporate Data Warehouse database.

Methods and Results

We retrospectively followed 69 574
VA
women, aged 30 to 79 years, from 2007 to 2017. Of these, 52% were whites (n=36 172), 42% were blacks (n=29 232), and 6% were Hispanics (n=4171). Risk factors and
ASCVD
events (nonfatal myocardial infarction, nonfatal stroke, and cardiac deaths) were identified using diagnostic and procedural codes from electronic health records. Then, within the same construct of the current American College of Cardiology/American Heart Association 10‐year
ASCVD
risk assessment models for women, coefficients for risks factors were recalculated using the
VA
national electronic health record data, stratified by race (hereafter,
VA
women model). Our study found a curvilinear association of aging with increased risk of 10‐year
ASCVD
event in
VA
women starting at ages as young as 30 years across all race groups. The
VA
women model performance in predicting
ASCVD
events at 10 years was mixed‐moderate in discrimination (C statistics, 0.61–0.64) but good in accuracy, as demonstrated by calibration plots approximating a 45° line.

Conclusions

The study finding, a curvilinear association of aging with increased
ASCVD
risk in
VA
women across all races, demonstrates the need for cardiovascular risk screening of younger
VA
women, aged <45 years.
Using Specialised Anti-Corruption Agencies to Combat Pervasive Corruption in Nigeria: A Critical Review of the ICPC and EFCC
Authors: Abdulrauf Lukman Adebisi
Published: June 2020

The use of specialised anti-corruption agencies (ACAs) to combat corruption is increasingly popular among African countries. This is no surprise considering the successes these agencies have recorded elsewhere in the world, on the strength of which they have been described as ‘the most innovative feature of the anti-corruption movement of the last two decades’. Yet while ACAs have been successful in other parts of the world, the same cannot be said of those in Africa generally and Nigeria in particular. Even with two ACAs – the Independent Corrupt Practices and Other Related Offences Commission (ICPC) and Economic and Financial Crimes Commission (EFCC) – corruption continues to soar in the country, making it necessary to examine the flaws of Nigeria’s ACAs. Focusing on a number of key characteristics of ACAs, this article analyses the role of the ICPC and EFCC in combating corruption in Nigeria. The main question the article seeks to answer is why corruption should be on the increase despite the fact that two specialised ACAs have been in existence for close to two decades.
Appraising Grazing Laws in Nigeria. Pastoralists versus Farmers
Authors: Mrabure Kingsley O. , Awhefeada Ufuoma V.
Published: June 2020

The paper highlights the historical development of grazing reserves in Nigeria, the recent violent clashes between pastoralists and farmers taking into consideration the effects of grazing on land, causes and consequences of farmer-pastoralist conflicts and the adequacy of grazing laws. The paper contends that the Grazing Reserve Law 1965 applicable only to States in Northern part of Nigeria have not adequately curb the incessant clashes between pastoralists and farmers and that some provisions of the National Grazing Reserve (Establishment) Bill 2016 conflict with farmers’ inalienable right to property as entrenched in the 1999 Constitution of Nigeria (as amended) and protection of propriety rights in land under the Land Use Act. The paper concludes by stating unambiguously that for lasting peace to reign between farmers and pastoralists. States should enact anti-grazing laws has done by Ekiti State which brought relative peace between pastoralists and farmers in the State.
Quo Vadis? From the Schoolyard to the Courtroom
Authors: Sytch Maxim , Kim Yong H.
Published: June 2020

Existing theories exploring how companies interact with the law stop short of unveiling whether and why companies can differentially pursue, interact with, and benefit from a particular legal environment. We theorize that companies can use social structures—shared educational and professional affiliations—between lawyers and judges to strategically pursue specific legal jurisdictions, influence judges’ discretion, and ultimately reap different legal outcomes from the same legal environment. Using data on such affiliations between lawyers and federal judges, we examine companies’ choice of U.S. federal district courts and their legal outcomes in patent infringement litigation from 1990 to 2013. Our results reveal that companies strategically pursue courts in which their lawyers have past educational or professional affiliations with the courts’ judges. If a desired judge is assigned to the case, a company leverages its lawyers’ social structures to tailor any legal communication to match that judge’s style. While such behavior results in a higher likelihood of winning a lawsuit, it also creates an inherent risk. In stacking their legal teams with lawyers who have connections to judges, companies often shortchange the human capital—lawyers’ skillsets—required to win a case, which adversely affects legal outcomes if the desired judge is not assigned to the case.