bluuebunny/crossref_metadata_2025_split huggingface dataset:
A retrospective study of the clinical phenotype and predictors of survival in non-Caucasian Hispanic patients with amyotrophic lateral sclerosis
Authors: Sánchez-Martínez Claudia Marisol , Choreño-Parra José Alberto , Nuñez-Orozco Lilia , Placencia-Álvarez Noel , Alvis-Castaño Laura Marcela , Guadarrama-Ortiz Parménides 
Published: October 2019

Abstract

Background
Little is known about the clinical phenotype of amyotrophic lateral sclerosis (ALS) in non-Caucasian populations. Here, we aimed to describe the clinical characteristics, prognostic factors and survival of Mexican patients with ALS.

Methods
We conducted a retrospective study by reviewing the medical records of patients with ALS that attended and were regularly followed at a third level hospital in Mexico City from 2000 to 2015. We calculated absolute and relative frequencies of the clinical characteristics from all the participants. We also estimated correlation coefficients between clinical features and overall survival. Additionally, survival rates were compared for all participants grouped according to different clinical features using the Kaplan-Meier method and the log-rank test.

Results
We enrolled 45 ALS patients, 53.33% had spinal-onset ALS and 46.66% presented bulbar ALS. The male/female ratio was 0.8. The mean age at onset of symptoms was 58.11 years. Mean survival time from onset was 64.73 ± 34.83 months. Cumulative survival rate after 5 years of disease onset was 44.44%. Age at onset and age at diagnosis inversely correlated with overall survival time. Also, we found that bulbar-onset, short diagnostic delay, percutaneous endoscopic gastrostomy, mechanical ventilation, and lower total cholesterol serum levels were associated with short survival.

Conclusions
The clinical characteristics of Mexican ALS patients differ from the disease phenotype observed in Caucasians. Nonetheless, the predictive value of certain well-recognized prognostic factors remains consistent in our population. The current study provides relevant information for a better understanding of prognostic factors in ALS patients from Mexico and other Latin American countries.
Subarachnoid haemorrhage due to intracranial vertebral artery dissection presenting with atypical cauda equina syndrome features: case report
Authors: Steele Lloyd , Raza Muhammad Hasan , Perry Richard , Rane Neil , Camp Sophie J. 
Published: October 2019

Abstract

Background
Failing to recognise the signs and symptoms of subarachnoid haemorrhage (SAH) causes diagnostic delay and may result in poorer outcomes. We report a rare case of SAH secondary to a vertebral artery dissection (VAD) that initially presented with cauda equina-like features, followed by symptoms more typical of SAH.

Case presentation
A 55-year-old man developed severe lower back pain after sudden movement. Over the next 5 days he developed paraesthesiaes in the feet, progressing to the torso gradually, and reported constipation and reduced sensation when passing urine. On day six he developed left facial palsy, and later gradual-onset headache and intermittent confusion.
Magnetic resonance imaging of the brain showed diffuse subarachnoid FLAIR hyperintensity, concerning for blood, including a focus of cortical/subcortical high signal in the left superior parietal lobule, which was confirmed by computed tomography. Digital subtraction angiography demonstrated a left VAD with a fusiform aneurysm.

Conclusion
We present a very rare case of intracranial VAD with SAH initially presenting with spinal symptoms. The majority of subsequent clinical features were consistent with a parietal focus of cortical subarachnoid blood, as observed on neuroimaging.
Treponema pallidum infection predicts sexually transmitted viral infections (hepatitis B virus, herpes simplex virus-2, and human immunodeficiency virus) among pregnant women from rural areas of Mwanza region, Tanzania
Authors: Ng’wamkai Gilbert , Msigwa Kalista V. , Chengula Damas , Mgaya Frank , Chuma Clotilda , Msemwa Betrand , Silago Vitus , Majigo Mtebe , Mshana Stephen E. , Mirambo Mariam M. 
Published: October 2019

AbstractBackgroundSexually transmitted infections (STIs) is a global health problem with increased risk and morbidities during pregnancy. This study investigated the magnitude of viral STIs among pregnant women from three rural hospitals/clinics providing antenatal care in Mwanza region, Tanzania.MethodsBetween February and May 2018, a total of 499 pregnant women were enrolled and tested for Human immunodeficiency virus (HIV), Herpes simplex virus-2 (HSV-2), Hepatitis B virus (HBV) and Hepatitis C virus (HCV) using rapid immunochromatographic tests and for syphilis using non-treponemal and treponemal antibody test.ResultsThe median age of enrolled women was 25 (IQR: 22–31) years. Seventy eight (15.6, 95% CI: 12–18) of women tested had at least one sexually transmitted viral infection. Specific prevalence of HIV, HBV, HCV, HSV-2 IgG and HSV-2 IgM were found to be 25(5.0%), 29(5.8%), 2(0.4%), 188(37.7%) and 24(4.8%), respectively. The odds of having viral infection was significantly high among women with positiveT. pallidumserostatus (adjusted odd ratio (aOR): 3.24, 95%CI; 1.2–85). By multivariable logistic regression analysis, history of STIs predicted HSV-2 IgM seropositivity (aOR: 3.70, 95%CI: 1.43–9.62) while parity (aOR: 1.23, 95%CI: 1.04–1.46) predicted HBV infection and syphilis positive results (aOR: 8.63, 95%CI: 2.81–26.45) predicted HIV infection.ConclusionA significant proportion of pregnant women in rural areas of Mwanza region has at least one sexually transmitted viral infection which is independently predicted by positiveT. pallidumserostatus. The strengthening and expansion of ANC screening package to include screening of STIs will ultimately reduce the viral STIs among pregnant women hence reduce associated morbidities and mortalities.
Severe colitis after PD-1 blockade with nivolumab in advanced melanoma patients: potential role of Th1-dominant immune response in immune-related adverse events: two case reports
Authors: Yoshino Koji , Nakayama Takayuki , Ito Ayumu , Sato Eiichi , Kitano Shigehisa 
Published: October 2019

AbstractBackgroundNivolumab is an immune checkpoint inhibitor specific to the programmed death 1 (PD-1) receptor. Nivolumab has shown clinical responses in many malignancies. Although immune-related adverse events (irAEs) associated with nivolumab are largely tolerable, severe irAEs have occurred in some patients. However, the mechanisms underlying the development of irAEs are not fully clarified.Case presentationWe report 2 patients with metastatic melanoma who developed colitis, an irAEs caused by nivolumab. Both patients experienced colitis after nivolumab administration. Pathological examination of the colon showed robust infiltration of CD8+cells and T-bet expressing CD4+cells in both cases, indicating helper T cells (Th) 1 to be responsible for the dominant response. Additionally, we observed the serum C-reactive protein level (CRP) as well as interleukin-6 (IL-6) reflected the clinical course of irAEs clearly in the two cases.ConclusionOur two cases suggested that the development of irAEs due to nivolumab is associated with Th1 dominant response. CRP as well as IL-6 was found to be a potential biomarker for irAEs. Our findings may help to understand the mechanisms underlying irAEs caused by nivolumab and manage irAEs in clinical practice.
Postoperative chemoradiotherapy is superior to postoperative chemotherapy alone in squamous cell lung cancer patients with limited N2 lymph node metastasis
Authors: Su Liyu , Chen Mingqiu , Su Huiyan , Dai Yaqing , Chen Shaoxing , Li Jiancheng 
Published: October 2019

Abstract

Background
The aim of the present study was to assess the efficacy of postoperative chemoradiotherapy (POCRT) following surgery in non-small-cell lung cancer patients with N2 lymph node metastasis (N2-NSCLC).

Methods
The clinical data of patients with N2-NSCLC treated with POCRT or postoperative chemotherapy (pCT) alone were retrospectively collected and reviewed. The overall survival (OS) rates were analyzed utilizing the Kaplan-Meier method and compared by the log-rank test. Cox regression analysis was used to determine factors significantly associated with survival. Propensity score matching (PSM) analysis was used to compensate for differences in baseline characteristics and OS was compared after matching.

Results
Between 2004 and 2014, a total of 175 patients fulfilled the inclusion criteria, 60 of whom were treated with POCRT, while 115 were administered pCT. The 1, 3 and 5-year OS rates in the POCRT and pCT groups were 98.3 vs. 86.1%, 71.7 vs. 53.0% and 45.7 vs. 39.0%, respectively (P = 0.019). Compared with pCT, POCRT improved OS in patients with squamous cell subtype (P = 0.010), no lymphovascular invasion (P = 0.006), pN2a (P = 0.006) or total number of metastatic lymph nodes ≤7 (P = 0.016). After PSM, these survival differences between POCRT and pCT remained significant in patients with squamous cell lung cancer (P = 0.010).

Conclusions
POCRT following complete resection may be beneficial for patients with squamous cell lung cancer, particularly those with limited nodal involvement.
GX15–070 (Obatoclax), a Bcl-2 family proteins inhibitor engenders apoptosis and pro-survival autophagy and increases Chemosensitivity in neuroblastoma
Authors: Cournoyer Sonia , Addioui Anissa , Belounis Assila , Beaunoyer Mona , Nyalendo Carine , Le Gall Roxane , Teira Pierre , Haddad Elie , Vassal Gilles , Sartelet Hervé 
Published: October 2019

AbstractBackgroundNeuroblastoma (NB) is a frequent pediatric tumor associated with poor prognosis. The disregulation of Bcl-2, an anti-apoptotic protein, is crucial for the tumoral development and chemoresistance. Autophagy is also implicated in tumor cell survival and chemoresistance. The aim of our study was to demonstrate therapeutic efficiency of GX 15–070, a pan-Bcl-2 family inhibitor, used alone and in combination with conventional drugs or with hydroxychloroquine (HCQ), an autophagy inhibitor.MethodsFive neuroblastoma cell lines were tested for the cytotoxic activity of GX 15–070 alone or in combination with cisplatin, doxorubicin, HCQ or Z-VAD-FMK a broad-spectrum caspase inhibitor. Apoptosis and autophagy levels were studied by western-blot and FACS. Orthotopic injections were performed on NOD/LtSz-scid/IL-2Rgamma null mice that were treated with either GX 15–070 alone or in combination with HCQ.ResultsSynergistic cytotoxicity was observed for the drug combination in all of the 5 neuroblastoma cell lines tested, including MYCN amplified lines and in cancer stem cells. GX 15–070 significantly increased apoptosis and autophagy in neuroblastoma cells as evidenced by increased levels of the autophagy marker, LC3-II. Inhibition of autophagy by HCQ, further increased the cytotoxicity of this combinatorial treatment, suggesting that autophagy induced by these agent plays a cytoprotective role. In vivo, GX 15–070 combined with HCQ significantly decreased the growth of the tumor and the number of distant metastases.ConclusionsBased on the synergistic effect of HCQ and GX 15–070 observed in this study, the combination of these two drugs may be utilized as a new therapeutic approach for neuroblastoma.
The release of tryptase from mast cells promote tumor cell metastasis via exosomes
Authors: Xiao Hui , He Mudan , Xie Guogang , Liu Yanan , Zhao Yuxia , Ye Xiong , Li Xingjing , Zhang Min 
Published: October 2019

Abstract

Background
Cancer cells release exosomes and can be taken up by mast cells (MCs), but the potential functional effects of MCs on tumor metastasis remain unknown.

Method
Exosomes were isolated from the lung adenocarcinoma cell line A549, and the uptake of PKH26-labeled exosomes by bone marrow MCs was examined via flow cytometry and fluorescence microscopy. Cytokines and tryptase in MC supernatant were analyzed using an ELISA kit, and the presence of tryptase was evaluated by Western blotting. Cell proliferation and migration were determined through CCK-8 and transwell assays. Proteins in the tryptase-JAK-STAT signaling pathway were detected by Western blotting.

Results
In this study, we show that exosomes from A549 cells can be taken up by MCs. Moreover, A549 exosomes contain stem cell factor (SCF) to MCs and subsequently induce the activation of MCs through SCF-KIT signal transduction, which leads to MC degranulation and the release of tryptase. Tryptase accelerates the proliferation and migration of human umbilical vein endothelial cells (HUVECs) through the JAK-STAT signaling pathway.

Conclusions
Our results reveal a mechanism for metastasis in which exosomes can transfer SCF to and activate MCs, which can affect the release of tryptase and the angiogenesis of HUVECs.
Dipeptidyl-peptidase-4 (DPP-4) inhibitor ameliorates 5-flurouracil induced intestinal mucositis
Authors: Lee Jung Min , Yoo In Kyung , Lee Jae Min , Kim Seung Han , Choi Hyuk Soon , Kim Eun Sun , Keum Bora , Seo Yeon Seok , Jeen Yoon Tae , Chun Hoon Jai , Lee Hong Sik , Um Soon Ho , Kim Chang Duck 
Published: October 2019

Abstract

Background
Chemotherapy-induced alimentary mucositis (AM) is difficult to prevent and treatment is rarely effective. Recent study have been showed that glucagon-like peptide (GLP)-1 and GLP-2 has protective in chemotherapy-induced AM. While the DPP-4 enzyme degrades this GLP-1, the DPP-4 inhibitor blocks the degradation process and raises the concentration of GLP-1. This study aimed to assess the role of DPP-4 inhibitor, a well-known hypoglycemic agent, on chemotherapy-induced AM.

Methods
Twenty-four 6-week-old male C57BL/6 mice were divided into 4 groups: control, 5-fluorouracil (5-FU), DPP-4 inhibitor, and saline (DPP-4i), and DPP-4 inhibitor and 5-FU (DPP-4i + 5-FU). Mucositis was induced by intraperitoneal injection of 5-FU (400 mg/kg). DPP-4 inhibitor (50 mg/kg) was administered orally for four days starting the day before 5-FU administration. Post 72 h of 5-FU injection, mice were sacrificed and body weight change, diarrhea score, villus height, villus/crypt ratio, histologic characteristics including goblet cell count, and mRNA expression of inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6, were assessed.

Results
Daily body weight change was not statistically significant between the 5-FU and the DPP-4i + 5-FU group (P = 0.571). Diarrhea score was significantly different between these two groups (P = 0.033). In the 5-FU group, the villus height was not maintained well, the epithelial lining was irregular, and inflammatory cell infiltration was observed. Goblet cell count in the DPP-4i + 5-FU group was significantly higher than in the 5-FU group (P = 0.007). However, in the DPP-4i + 5-FU group, the villus height, epithelial lining, and crypt structure were better maintained than in the 5-FU group. Compared with the control group, mRNA expression of TNF-α was significantly up-regulated in the 5-FU group. Moreover, mRNA expression of TNF-α in the DPP-4i + 5-FU group was down-regulated compared to the 5-FU group. However, IL-6 in the 5-FU group was significantly down-regulated compared to the control, there was no significant difference in expression of IL-6 between the 5-FU and DPP4i + 5-FU group.

Conclusion
DPP-4 inhibitor can improve 5-FU induced AM and, therefore, has potential as an alternative treatment for chemotherapy-induced AM.
Furosemide use and survival in patients with esophageal or gastric cancer: a population-based cohort study
Authors: Liu Peipei , McMenamin Úna C. , Spence Andrew D. , Johnston Brian T. , Coleman Helen G. , Cardwell Chris R. 
Published: October 2019

Abstract

Background
Pre-clinical studies have shown that furosemide slows cancer cell growth by acting on the Na-K-2Cl transporter, particularly for gastric cancer cells. However, epidemiological studies have not investigated furosemide use and mortality in gastroesophageal cancer patients. Consequently, we conducted a population-based study to investigate whether furosemide use is associated with reduced cancer-specific mortality in esophageal/gastric cancer patients.

Methods
A cohort of patients newly diagnosed with esophageal or gastric cancer between 1998 and 2013 were identified from English cancer registries and linked to the Clinical Practice Research Datalink to provide prescription records and the Office of National Statistics to provide death data up to September 2015. Time-dependant Cox-regression models were used to calculate hazard ratios (HRs) comparing cancer-specific mortality in furosemide users with non-users. Analyses were repeated restricting to patients with common furosemide indications (heart failure, myocardial infarction, edema or hypertension) to reduce potential confounding.

Results
The cohort contained 2708 esophageal cancer patients and 2377 gastric cancer patients, amongst whom 1844 and 1467 cancer-specific deaths occurred, respectively. Furosemide use was not associated with reduced cancer-specific mortality overall (adjusted HR in esophageal cancer = 1.28, 95% CI 1.10, 1.50 and in gastric cancer = 1.27, 95% CI 1.08, 1.50) or when restricted to patients with furosemide indications before cancer diagnosis (adjusted HR in esophageal cancer = 1.07, 95% CI 0.88, 1.30 and in gastric cancer = 1.18, 95% CI 0.96, 1.46).

Conclusions
In this large population-based cohort study, furosemide was not associated with reduced cancer-specific mortality in patients with esophageal or gastric cancer.
Clinical significance of serum PSA in breast cancer patients
Authors: Hanamura Toru , Ohno Koichi , Hokibara Shinya , Murasawa Hideki , Nakamura Toshitsugu , Watanabe Hidehiko , Kaizuka Machiko , Sawano Shinji , Koyama Hiroshi , Ito Ken-ichi 
Published: October 2019

Abstract

Background
Recent preclinical data suggest that androgen receptor (AR) signaling plays a significant role in subsets of breast cancer. Clinical trials testing AR-targeting therapies in breast cancer have been conducted. Assessment of AR-signal in breast cancer tissue maybe useful for treatment selections. Prostate specific antigen (PSA) is the product of an androgen-responsive gene. Serum PSA (sPSA) can be detected in women by a highly sensitive assay although the concentration is much lower than that observed in males. We investigated if sPSA reflects tumor biology, including AR signaling in breast cancer patients.

Methods
In this study, 132 healthy controls and 144 breast cancer patients were enrolled. sPSA was evaluated by the chemiluminescent enzyme immunoassay (CLEIA) method. Correlations between sPSA and the various clinicopathological factors were analyzed.

Results
In post-menopausal state, sPSA detection rate was significantly higher in breast cancer patients compared with controls (27.4% vs 11.3%: p = 0.0090), but not in the whole cohort (29.2% vs 25.8%: p = 0.5265) or pre-menopausal subgroup (37.0% vs 42.6%: p = 0.6231). In post-menopausal breast cancer cases, higher sPSA value was associated with clinic-pathological factors including the expression of AR protein in primary legion. In a correlation analysis of quantitative data limited to post-menopausal metastatic breast cancer (MBC), sPSA was positively, albeit weakly correlated with clinic-pathological features including serum testosterone levels and AR positivity.

Conclusions
Our data suggest that sPSA may reflect tumor biological properties including AR activity in post-menopausal breast cancer.
Metachronous ovarian endometrioid carcinomas in a patient with a PTEN variant: case report of incidentally detected Cowden syndrome
Authors: Matsubayashi Hiroyuki , Higashigawa Satomi , Kiyozumi Yoshimi , Horiuchi Yasue , Hirashima Yasuyuki , Kado Nobuhiro , Abe Masato , Ohishi Takuma , Ohnami Sumiko , Urakami Kenichi , Yamaguchi Ken 
Published: October 2019

Abstract

Background
Somatic PTEN mutation occurs in a proportion of ovarian endometrioid carcinomas. However, these cancers have seldom been reported in diseases associated with germline PTEN variants, such as Cowden syndrome (CS).

Case presentation
The present case was a 39-year-old woman with a left ovarian carcinoma who demonstrated a germline splice variant of PTEN (c.1026 + 1G > T) following genome-wide whole exome sequencing of her germline DNA. Histology of her resected tumor revealed endometrioid carcinoma of the same type as a right ovarian cancer resected eight years previously. These tumors showed null immunostaining for PTEN. She was genetically diagnosed with CS. Despite her clinical examinations had demonstrated several characteristic findings of CS, including mammary fibroma, esophageal and skin papilloma, colonic hamartoma, uterine myoma, and lipoma, the clinicians could not approach this diagnosis.

Conclusion
Ovarian endometrioid carcinoma is generally thought to develop from endometrial tissue menstruated from the uterus and implanted on the ovary. To date, ovarian cancers have not been listed as CS-related cancers; however, ovarian endometrioid cancer can have a potential association with CS in endometriosis cases.
Prenatal pet keeping and caregiver-reported attention deficit hyperactivity disorder through preadolescence in a United States birth cohort
Authors: Cassidy-Bushrow Andrea E. , Sitarik Alexandra R. , Johnson-Hooper Tisa M. , Phillips Jannel M. , Jones Kyra , Johnson Christine Cole , Straughen Jennifer K. 
Published: October 2019

Abstract

Background
While the keeping of pets has been shown to protect against childhood allergic disease and obesity, less is known regarding potential associations of prenatal pet keeping and attention deficit hyperactivity disorder (ADHD). We sought to examine the associations between prenatal dog or cat keeping with caregiver-reported ADHD in preadolescents in the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS) birth cohort (N = 1258).

Methods
At an interview with the caregiver at child age 10–12 years, caregivers reported if the WHEALS child had ever been diagnosed with ADHD. Similarly, during an interview with the mother prenatally, pet keeping (defined as dog or cat kept inside ≥1 h/day) was ascertained. Logistic regression models were fit to examine the association of prenatal pet keeping (dog keeping and cat keeping, separately) with ADHD.

Results
A subset of 627 children were included in the analyses: 93 who had ADHD and 534 with neurotypical development. After accounting for confounders and loss to follow-up, maternal prenatal dog exposure was associated with 2.23 times (95% CI: 1.15, 4.31; p = 0.017) greater odds of ADHD among boys. Prenatal dog keeping was not statistically significantly associated with ADHD in girls (odds ratio = 0.27, 95% CI: 0.06, 1.12; p = 0.070). Prenatal cat keeping was not associated with ADHD.

Conclusions
In boys, but not girls, maternal prenatal dog keeping was positively associated with ADHD. Further study to confirm these findings and to identify potential mechanisms of this association (e.g., modification of the gut microbiome, exposure to environmental toxicants or pet-related medications) is needed.