bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemical overexpression of BCL-2 protein predicts an inferior survival in patients with primary central nervous system diffuse large B-cell lymphoma
Authors: Chen Yi , Chen Hong , Chen Lushan , Zheng Xiaoyun , Yang Xiaozhu , Zheng Zhihong , Zheng Jing , Yang Ting , Liu Tingbo , Yang Yinghong , Hu Jianda 
Published: November 2019

Abstract
This study was designed to analyze the clinical characteristics and prognostic value of c-MYC and BCL-2 proteins expression in patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL).
82 patients newly diagnosed with PCNS-DLBCL, from January 2008 to November 2018, were enrolled in this study. Clinical characteristics, immunohistochemical features, laboratory examinations, and treatment outcome were analyzed among these patients.
Among these 82 cases, 45 were males (54.9%) and 37 were females (45.1%). Age ranged from 16 to 78 years old, and 29 patients (35.4%) were elder than 60 years old, with median age at 57 years old. According to Hans classification, 25 were accounted for origin of germinal center B-cell (GCB) subtype (30.5%) and 49 were accounted for non-GCB subtype (59.8%), respectively. Eight patients were unclassified due to lack of detailed pathological results. The median survival of these 82 patients was 30 months, and 1-year, 3-year, and 5-year overall survival (OS) rate was 59.7%, 44.6%, and 34.1%, respectively. Patients treated with sequential HD-MTX based chemotherapies showed a superior prognosis than those without. In combination with rituximab, the outcome was further improved. The median OS was 55 months in HD-MTX + R group, 27 months in HD-MTX group, and 9 months in other groups, respectively. Univariate analysis identified age ≥60, ECOG score ≥ 2 points, and overexpression of BCL-2 protein (≥85%) were adverse prognostic factors for OS. Co-expression of c-MYC (≥40%) and BCL-2 (≥50%) proteins was associated with poor ECOG score, high Ki-67 expression, and trended towards an inferior outcome. Gender, lesion location, number of lesions, lactic dehydrogenase (LDH), cell of origin, BCL-6 protein expression, expression of c-MYC protein alone and Ki-67 ≥85% had no significant impact on OS.
In patients with PCNS-DLBCL, age ≥60 years old, ECOG score ≥2 points, and overexpression of BCL-2 protein (≥85%) were associated with a poor survival. HD-MTX based chemotherapies in combination with rituximab could improve the prognosis.
Efficacy and safety of HT080 for lower urinary tract symptoms associated with benign prostatic hyperplasia
Authors: Song Jungbin , Lee Seung Hwan , Kim Hocheol 
Published: November 2019

Abstract

Background:
Lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) are one of the most common conditions seen in middle-aged and elderly men and threaten their quality of life. Since conventional pharmacotherapy for LUTS/BPH can lead to sexual side effects, herbal therapies are widely used as complementary and alternative treatments worldwide. HT080 is an herbal extract of Cinnamomum cassia and Rosa Laevigata, both of which have been used to treat symptoms typically associated with BPH in traditional Asian medicine. The aims of this trial are to assess whether HT080 can alleviate LUTS/BPH in middle-aged and elderly men, and to investigate the safety of HT080.

Methods/design:
A double-blind, randomized, placebo-controlled, two-arm parallel group trial will be conducted in men with moderate LUTS/BPH. A total of 100 eligible men aged 40 to 75 years with an International Prostate Symptom Score of 8 to 19 will be randomized in a 1:1 ratio and receive either HT080 (500 mg) or placebo twice a day for 12 weeks. All participants will be evaluated for efficacy and safety at baseline and weeks 6 and 12. The primary endpoint is the change in International Prostate Symptom Score between baseline and week 12. The secondary efficacy variables are uroflowmetry parameters (maximal urinary flow rate and post-void residual volume), serum prostate-specific antigen, testosterone, and dihydrotestosterone levels, the International Index of Erectile Function score, and participant-reported global response assessment scores. The safety assessments include adverse events, laboratory tests results, vital signs, and physical examination.

Discussion:
This is a first-in human trial designed to investigate the efficacy and safety of HT080 among middle-aged and elderly men with LUTS/BPH. This prospective study with a double-blind randomized design will provide high-quality evidence supporting the use of HT080 for LUTS/BPH.

Trial registration:
Korean Clinical Research Information Service (KCT0004286) Registered September 6, 2019.
Hepatotoxicity and hematologic complications induced by fusidic acid in a patient with hepatitis B cirrhosis
Authors: He Zhong-Fang , Chen Lin , Zhang Jian-Ping , Wang Qing-qing 
Published: November 2019

Abstract

Rationale:
Fusidic acid (FA) is an active agent against gram-positive bacteria such as Staphylococcus, it is generally well tolerated and the major adverse effects are mild gastrointestinal discomfort, diarrhea, and headache. However, some rare side effects such as granulocytopenia and thrombocytopenia have also been reported. Here we report a case of FA-induced hepatotoxicity and hematologic toxicity.

Patient concerns:
A 54-year-old woman with hepatitis B cirrhosis was referred to us because of fever, Staphylococcus aureus was identified in the twice blood culture, and intravenous FA was given (0.5 g, q8 hours). Twelve days after FA therapy, she developed nausea and jaundice. Meanwhile, complete blood cell count showed neutropenia (white blood cell count of 1360/μL, neutrophil of 619/μL) and aggravated thrombocytopenia (platelet count of 18,000/μL). Adverse drug reaction was suspected, and FA was stopped immediately, after 1 day of discontinuation of FA, nose bleeding occurred and the platelet count declined further and reached the lowest value of 4000/μL.

Diagnoses:
Hepatotoxicity and hematologic complications induced by FA were diagnosed.

Interventions and outcomes:
The FA was stopped immediately, and concentrated platelet transfusion was used. Five days after withdrawal of FA, jaundice resolved and the hematologic index returned to the level before the medication.

Lessons:
Hematologic adverse effect accompanying with hepatotoxicity may be induced by FA. Though the risk is rather low, it should not be overlooked.
Diagnostic value of cytology, thyroglobulin, and combination of them in fine-needle aspiration of metastatic lymph nodes in patients with differentiated thyroid cancer
Authors: Xu Yixin , Wu Dapeng , Wu Wenting , Jiang Jian , Xi Cheng , Ye Nianyuan , Wang Yibo , Xu Xuezhong 
Published: November 2019

Abstract

Background:
To investigate the diagnostic performance of cytology (fine-needle aspiration cytology [FNAC]), thyroglobulin (fine-needle aspiration thyroglobulin [FNA-Tg]), and combination of them in the washout of fine-needle aspiration for those patients who have suspicious metastatic lymph nodes of differentiated thyroid cancer.

Methods:
Databases, including PubMed, EMbase, Web of Science and Cochrane Library were searched up to June 2019. The quality assessment of diagnostic accuracy scale-2 was used to conduct quality assessments, and publication bias was evaluated using the Deeks funnel plot. STATA version 14.0 was used to perform the meta-analysis.

Results:
A total of 2257 patients with 2786 samples of suspicious metastatic lymph nodes of differentiated thyroid cancer were included in the meta-analysis. The results showed that the diagnostic value for detecting lymph node metastasis of differentiated thyroid cancer was as follows: combination of FNAC and FNA-Tg > FNA-Tg > FNAC. All differences of superiority among them are statistically significant. The sensitivity of the combination was 0.968 (95% confidence interval [CI]: 0.942–0.983), the specificity was 0.932 (95% CI: 0.856–0.969), the diagnostic score was 6.036 (95% CI: 4.892–7.181), the diagnostic odds ratio was 418.424 (95% CI: 133.167–1314.729), and the score of summary receiver operating characteristic was 0.99 (95% CI: 0.97–0.99).

Conclusions:
The combination of FNAC and FNA-Tg is an excellent procedure in diagnosis of lymph nodes metastasis of patients with differentiated thyroid cancer, which should be highly recommended.
Analysis of mortality prognostic factors using model for end-stage liver disease with incorporation of serum-sodium classification for liver cirrhosis complications
Authors: Kim Yuna , Kim Kyunghee , Jang Insil 
Published: November 2019

Abstract
Since the progression of cirrhosis is accelerated each time a complication recurs, the management and treatment of the complication is critical in enhancement of the quality of life and expectation of life in patients. The use of model for end-stage liver disease with incorporation of serum-sodium (MELD-Na) with physiological indicators can be used to assess severity and differentiate therapeutic interventions.
This study is aimed to determine the mean survival period and cumulative survival rate by classifying patients into high-risk and low-risk groups based on MELD-Na, a predictor of mortality in liver disease, and to investigate the mortality prognostic factors.
A retrospective cohort study, which follows the STROBE checklist, was performed. 263 patients who were diagnosed with liver cirrhosis complications for the first time and hospitalized were selected as the subjects of this study. The collected data were analyzed based on the survival package provided by the statistical program R version 3.4.2.
Subjects were classified into high-risk and low-risk groups using MELD-Na 14 points where sensitivity and specificity crossed the cut-off point. Gender, age, and primary caregiver were significant variables in the mortality high-risk group, and AST, albumin, and primary caregiver were significant variables in the mortality low-risk group. Based on these mortality prognostic factors, it is possible to present the factors affecting mortality in patients who were diagnosed with liver cirrhosis complications for the first time. The classification of patients by risk level could be the foundation to provide accurate guidelines for management and it is necessary to modify prognostic factors and apply nursing interventions to manage complications.
Psoas abscess associated with aortic endograft infection caused by bacteremia of Listeria monocytogenes
Authors: Ma Jen-Wen , Hu Sung-Yuan , Lin Tzu-Chieh , Tsai Che-An 
Published: November 2019

Abstract

Rationale:
Endograft infection following endovascular stent for aortic aneurysm is rare (0.6%–3%), but it results in high mortality rate of 25% to 88%.

Patient concerns:
A 66-year-old hypertensive man underwent an endovascular stent graft for abdominal aortic aneurysm 18 months ago. Recurrent episodes of fever, chills, and abdominal fullness occurred 6 months ago before this admission. Laboratory data showed 20 mg/dL of C-reactive protein and abdominal computed tomography (CT) revealed an aortic endoleak at an urban hospital, so 4-day course of intravenous (IV) amoxicillin/clavulanic acid was given and he was discharged after fever subsided. He was admitted to our hospital due to fever, chills, and watery diarrhea for 1 day. Abdominal CT showed left psoas abscess associated with endograft infection. Blood culture grew Listeria monocytogenes.

Diagnosis:
Left psoas abscess associated with endograft infection caused by bacteremia of Listeria monocytogenes.

Interventions:
IV ampicillin with 8 days of synergistic gentamicin was prescribed and it created satisfactory response. Ampicillin was continued for 30 days and then shifted to IV co-trimoxazole for 12 days.

Outcomes:
He remained asymptomatic with a decline of CRP to 0.36 mg/dL and ESR to 39 mm/h. He was discharged on the 44th hospital day. Orally SMX/TMP was prescribed for 13.5 months.

Lessons:
Only few cases of aortic endograft infection caused by Listeria monocytogenes had been reported. In selected cases, particularly with smoldering presentations and high operative risk, endograft retention with a prolonged antimicrobial therapy seem plausible as an initial therapeutic option, complemented with percutaneous drainage or surgical debridement if necessary.
Characteristics of nocardiosis patients with different immune status from a Chinese tertiary general hospital during 8-year period
Authors: Huang Lei , Sun Liying , Yan Yan 
Published: November 2019

Abstract

Nocardia is an opportunistic pathogen from environment, which is generally thought to infect immunosuppressed patients (ISPs), but recent studies showed it could also cause infections in immunocompetent patients (ICPs).
The aim of this study was to compare the clinical characteristics, patients’ outcome, Nocardia species’ identification, and antibiotic susceptibility profiles of nocardiosis between ICPs and ISPs.
The detailed clinical data were collected from all the nonrepetitive nocardiosis patients during 2011 and 2018, from a tertiary general hospital in Beijing, China. Then each Nocardia isolate was identified to species level by DNA sequencing. The antibiotic susceptibility testing was performed by E test method, and interpreted following CLSI M24 document. The clinical and microbiological characteristics between ICPs and ISPs were compared statistically.
A total of 23 nonrepetitive nocardiosis patients with detailed clinical data were enrolled in this study. Among them, 9 were ICPs and 14 were ISPs. All the skin and soft tissue infections occurred in ICPs (33.3% vs 0%, P < .05). Bronchiectasis occurred more frequently in ICPs (44.4% vs 21.4%), whereas chronic kidney diseases and coinfection with aspergillosis occurred more frequently in ISPs (35.7% vs 0%, 35.7% vs 0%, respectively), although they did not reach the statistical significance. There were no significant differences in other clinical characteristics, Nocardia species’ identification, and antibiotic susceptibility between ISPs and ICPs (P > .05).
Nocardiosis could occur in both ISPs and ICPs. Skin and soft tissue infection and bronchiectasis occurred more frequently in ICPs. Chronic kidney diseases and co-infection with aspergillosis occurred more frequently in ISPs. These characteristics should be noticed by physicians in diagnosis of nocardiosis.
Plasma proteome analysis of patients with hereditary transthyretin-mediated (hATTR) amyloidosis establishes neurofilament light chain (NfL) as a biomarker of disease and treatment response
Authors: Ticau Simina , Sridharan Gautham V , Tsour Shira , Cantley William L , Chan Amy , Gilbert Jason A , Erbe David , Aldinc Emre , Reilly Mary M , Adams David , Polydefkis Michael , Fitzgerald Kevin , Vaishnaw Akshay , Nioi Paul 
Published: November 2019

SummaryBackgroundHereditary transthyretin-mediated (hATTR) amyloidosis is a rare, progressively debilitating, and fatal disease caused by deposition of aggregated transthyretin amyloid in multiple organs and tissues. Highly variable disease penetrance has made it difficult to predict disease onset and progression. Clinically validated, non-invasive plasma biomarkers may facilitate earlier diagnosis and aid monitoring of disease progression.MethodsPlasma levels of >1000 proteins were measured in patients with hATTR amyloidosis with polyneuropathy who received either placebo or patisiran in the phase 3 APOLLO study (NCT01960348) and in a cohort of healthy individuals. The impact of patisiran treatment on the time profile of each protein was determined by a linear mixed model at 0, 9, and 18 months. Neurofilament light chain (NfL) protein was further assessed using an orthogonal quantitative approach.FindingsA significant change in the levels of 66 proteins was observed with patisiran vs placebo, with change in NfL, a marker of neuronal damage, most significant (p<10−20). Analysis of the changes in protein levels demonstrated that the proteome of patients treated with patisiran trended towards healthy individuals at 18 months. Plasma NfL levels in healthy controls were four-fold lower than in patients with hATTR amyloidosis with polyneuropathy (16·3 [SD 12·0] pg/mL vs 69·4 [SD 42·1] pg/mL, p<10−16). Levels of NfL at 18 months increased with placebo (99·5 [SD 60·1] pg/mL) and decreased with patisiran treatment (48·8 [SD 29·9] pg/mL). At 18 months, improvement in modified Neuropathy Impairment Score+7 (mNIS+7) in patisiran-treated patients significantly correlated with a reduction in NfL levels (R=0·43, p<10−7).InterpretationThe observed correlation of NfL reduction with patisiran treatment and improvement in mNIS+7 suggests it may serve as a biomarker of nerve damage and polyneuropathy in hATTR amyloidosis. This biomarker may enable earlier diagnosis of polyneuropathy in patients with hATTR amyloidosis and facilitate monitoring of disease progression.
Structural basis for the binding selectivity of human CDY chromodomains
Authors: Dong Cheng , Liu Yanli , Lyu Tian-Jie , Beldar Serap , Lamb Kelsey N. , Tempel Wolfram , Li Yanjun , Li Zoey , James Lindsey I. , Qin Su , Wang Yun , Min Jinrong 
Published: November 2019

AbstractThe CDY (Chromodomain on the Y) family is a small family of chromodomain containing proteins, whose chromodomains closely resemble those in HP1 and Polycomb. The CDY proteins play an essential role in normal spermatogenesis and brain development. Dysregulation of their expression has been linked to male infertility and various neurological diseases. Like the chromodomains of HP1 and Polycomb, the CDY chromodomains also recognize the lysine-methylated ARKS motif embedded in histone and non-histone proteins. Interestingly, the CDY chromodomains exhibit different binding preferences for the lysine-methylated ARKS motif in different sequence contexts. Here, we present the structural basis for selective binding of CDY1 to H3K9me3 and preferential binding of CDYL2 to H3tK27me3 over H3K27me3. Based on our structural, binding and mutagenesis data, we synthesized a more CDYL1/2 selective peptidic ligand UNC4850. Our work provides critical implications that CDYL1b’s role in the regulation of neural development is dependent on its recognition of lysine-methylated ARKS motifs.
Stochastic model of T Cell repolarization during target elimination (I)
Authors: Hornak I. , Rieger H. 
Published: November 2019

AbstractCytotoxic T lymphocytes (T) and natural killer (NK) cells are the main cytotoxic killer cells of the human body to eliminate pathogen-infected or tumorigenic cells (i.e. target cells). Once a NK or T cell has identified a target cell, they form a tight contact zone, the immunological synapse (IS). One then observes a re-polarization of the cell involving the rotation of the microtubule (MT) half-spindle and a movement of the microtubule organizing center (MTOC) to a position that is just underneath the plasma membrane at the center of the IS. Concomitantly a massive relocation of organelles attached to MTs is observed, including the Golgi apparatus, lytic granules and mitochondria. Since the mechanism of this relocation is still elusive we devise a theoretical model for the molecular motor driven motion of the MT half-spindle confined between plasma membrane and nucleus during T cell polarization. We analyze different scenarios currently discussed in the literature, the cortical sliding and the capture-shrinkage mechanisms, and compare quantitative predictions about the spatio-temporal evolution of MTOC position and spindle morphology with experimental observations. The model predicts the experimentally observed biphasic nature of the repositioning process due to an interplay between spindle geometry and motor forces and confirms the dominance of the capture-shrinkage over the cortical sliding mechanism when MTOC and IS are initially diametrically opposed. We also find that the two mechanisms act synergetically, thereby reducing the resources necessary for repositioning. Moreover, it turns out that the localization of dyneins in the pSMAC facilitates their interaction with the MTs. Our model also opens a way to infer details of the dynein distribution from the experimentally observed features of the MT half-spindle dynamics. In a subsequent publication we will address the issue of general initial configurations and situations in which the T cell established two immunological synapses.
A novel system to map protein interactions reveals evolutionarily conserved immune evasion pathways on transmissible cancers
Authors: Flies Andrew S. , Darby Jocelyn M. , Lennard Patrick R. , Murphy Peter R. , Ong Chrissie E. B. , Pinfold Terry L. , Lyons A. Bruce , Woods Gregory M. , Patchett Amanda L. 
Published: November 2019

ABSTRACTImmune checkpoint immunotherapy has revolutionized medicine, but translational success for new treatments remains low. Around 40% of humans and Tasmanian devils (Sarcophilus harrisii) develop cancer in their lifetime, compared to less than 10% for most species. Additionally, devils are affected by two of the three known transmissible cancers in mammals. Unfortunately, little is known about of immune checkpoints in devils and other non-model species, largely due to a lack of species-specific reagents. We developed a simple cut-and-paste reagent development method applicable to any vertebrate species and show that immune checkpoint interactions are conserved across 160 million years of evolution. The inhibitory checkpoint molecule CD200 is highly expressed on devil facial tumor cells. We are the first to demonstrate that co-expression of CD200R1 can block CD200 expression. The evolutionarily conserved pathways suggest that naturally occurring cancers in devils and other species can serve as models for understanding cancer and immunological tolerance.GRAPHICAL ABSTRACT
Reward certainty and preference bias selectively shape voluntary decisions
Authors: Zajkowski Wojciech , Krzemiński Dominik , Barone Jacopo , Evans Lisa , Zhang Jiaxiang 
Published: November 2019

AbstractChoosing between equally valued options can be a conundrum, for which classical decision theories predicted a prolonged response time (RT). Paradoxically, a rational decision-maker would need no deliberative thinking in this scenario, as outcomes of alternatives are indifferent. How individuals choose between equal options remain unclear. Here, we characterized the neurocognitive processes underlying such voluntary decisions, by integrating advanced cognitive modelling and EEG recording in a probabilistic reward task, in which human participants chose between pairs of cues associated with identical reward probabilities at different levels. We showed that higher reward certainty accelerated RT. At each certainty level, participants preferred to choose one cue faster and more frequently over the other. The behavioral effects on RT persisted in simple reactions to reward cues. By using hierarchical Bayesian parameter estimation for an accumulator model, we showed that the certainty and preference effects were independently associated with the rate of evidence accumulation during decisions, but not with visual encoding or motor execution latencies. Time-resolved multivariate pattern classification of EEG evoked response identified significant representations of reward certainty and preference choices as early as 120 ms after stimulus onset, with spatial relevance patterns maximal in middle central and parietal electrodes. Furthermore, EEG-informed computational modelling showed that the rate of change between N100 and P300 event-related potentials reflected changes in the model-derived rate of evidence accumulation on a trial-by-trial basis. Our findings suggested that reward certainty and preference collectively shaped voluntary decisions between equal options, providing a mechanism to prevent indecision or random behavior.