bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repair of base damage within break-induced replication intermediates promotes kataegis associated with chromosome rearrangements
Authors: Elango Rajula , Osia Beth , Harcy Victoria , Malc Ewa , Mieczkowski Piotr A , Roberts Steven A , Malkova Anna 
Published: August 2019

AbstractBreak induced replication (BIR) is a double strand break repair pathway that can promote genetic instabilities similar to those observed in cancer. Instead of a replication fork, BIR is driven by a migration bubble where asynchronous synthesis between leading and lagging strands leads to accumulation of single-stranded DNA (ssDNA) that promotes mutation. However, the details of the mechanism of mutagenesis, including the identity of the participating proteins, remain unknown. Using yeast as a model, we demonstrate that mutagenic ssDNA is formed at multiple positions along the BIR track and that Pol ζ is responsible for the majority of both spontaneous and damage-induced base substitutions during BIR. We also report that BIR creates a potent substrate for APOBEC3A (A3A) cytidine deaminase that can promote formation of mutation clusters along the entire track of BIR. Finally, we demonstrate that uracil glycosylase initiates the bypass of DNA damage induced by A3A in the context of BIR without formation of base substitutions, but instead this pathway frequently leads to chromosomal rearrangements. Together, the expression of A3A during BIR in yeast recapitulates the main features of APOBEC-induced kataegis in human cancers, suggesting that BIR might represent an important source of these hyper-mutagenic events.
Munc18-1-interacting protein 3 mitigates renal fibrosis through protection of tubular epithelial cells from apoptosis
Authors: Nasu Kahori , Kawakami Takahisa , Shinohara Akinari , Sakamoto Takeharu , Nangaku Masaomi 
Published: August 2019

AbstractBackgroundTubulointerstitial fibrosis is a hallmark of chronic kidney disease (CKD), and is initiated by tubular epithelial cell (TEC) injury. Hypoxia promotes tubular cell death, fibrosis and CKD progression. Munc18-1-interacting protein 3 (Mint3) is a molecule that activates hypoxia-inducible factors (HIFs) by binding and suppressing factor inhibiting HIF-1 (FIH). However, the role of Mint3 in tubulointerstitial fibrosis remains unknown.MethodsWe induced fibrosis of the kidney after unilateral ischemia–reperfusion injury (uIRI) in Mint3-knockout and littermate wild-type mice. The duration of ischemia was 23 min and the kidneys were harvested at 24 h and 7 days after ischemia–reperfusion. The function of Mint3 was further investigated by using mouse cortical tubular (MCT) cells, which were treated with Mint3 and/or FIH small interfering RNA and exposed to normoxia or hypoxia.ResultsKnockout of Mint3 did not affect the acute injury induced by uIRI, but exacerbated the tubulointerstitial fibrosis, accompanied by an increase in TEC apoptosis. Consistently, hypoxia-induced apoptosis of MCT cells was aggravated by Mint3 knockdown. Unexpectedly, the additional knockdown of FIH did not suppress the increase in apoptosis by Mint3 knockdown, demonstrating the irrelevance of the FIH/HIF pathway. Therefore, we next focused on nuclear factor (NF)-κB, which has an anti-apoptotic role. Indeed, not only the expression of the inhibitory NF-κB p50 but also the DNA-binding activity of p50/p50 homodimer was increased by knockdown of Mint3 in the TECs, along with the decreased expressions of the NF-κB-targeted anti-apoptotic genes. An increase in NF-κB p50 was also confirmed in Mint3-knockout kidneys.ConclusionsMint3 in epithelial cells protects the cells from apoptosis by up-regulating anti-apoptotic effects of NF-κB, leading to fibrosis suppression. This new pathophysiology of tubulointerstitial fibrosis could be a target of future therapy for CKD.
An Empirical Validation of the Within-subject Biospecimens Pooling Approach to Minimize Exposure Misclassification in Biomarker-based Studies
Authors: Vernet Céline , Philippat Claire , Agier Lydiane , Calafat Antonia M. , Ye Xiaoyun , Lyon-Caen Sarah , Hainaut Pierre , Siroux Valérie , Schisterman Enrique F. , Slama Rémy 
Published: August 2019

Background:
Within-subject biospecimens pooling can theoretically reduce bias in dose–response functions from biomarker-based studies when exposure assessment suffers from classical-type error. However, collecting many urine voids each day is cumbersome. We evaluated the empirical validity of a within-subject pooling approach and compared several options to avoid sampling each void.

Methods:
In 16 pregnant women who collected a spot of each urine void over several nonconsecutive weeks, we compared concentrations of 10 phenols in daily, weekly, and pregnancy within-subject pools. We pooled either three or all daily samples. In a simulation study using these data, we quantified bias in dose–response functions when using one to 20 urine samples per subject to assess methylparaben (a compound with moderate within-subject variability) and bisphenol A (high variability) exposures.

Results:
Correlations between exposure estimates from pools of all and of only three voids per day were above 0.80 for all time windows and compounds, except for benzophenone-3 and triclosan in the daily time window (correlations, 0.57–0.68). With one spot sample to assess pregnancy exposure, correlations were all below 0.74. Using only one biospecimen led to attenuation bias in the dose–response functions of 29% (methylparaben) and 69% (bisphenol A); four samples for methylparaben and 18 for bisphenol A decreased bias to 10%.

Conclusions:
For nonpersistent chemicals, collecting and pooling three samples per day instead of all daily samples efficiently estimates exposures over a week or more. Collecting around 20 biospecimens can strongly limit attenuation bias for nonpersistent chemicals such as bisphenol A.
Perineal Talc Use, Douching, and the Risk of Uterine Cancer
Authors: O’Brien Katie M. , D’Aloisio Aimee A. , Shi Min , Murphy John D. , Sandler Dale P. , Weinberg Clarice R. 
Published: August 2019

Background:
Perineal talc use and douching could affect the risk of uterine cancer through several possible pathways, including inflammation response, microbiota changes, or endocrine disruption. Two previous cohort studies of the association between talc use and uterine cancer have reported weak positive associations, but we know of no previous evaluations of the relationship between douching and uterine cancer.

Methods:
Using a large prospective cohort, we examined the relationship between incident uterine cancer and self-reported use of talc or douche using Cox proportional hazards models.

Results:
After excluding those with prior hysterectomy, 271 of 33,609 women reported incident uterine cancer (mean follow-up = 8.3 years in noncases; maximum 12.6 years). Overall, 26% of women reported ever using talc and 15% reported ever having douched. Ever talc use was associated with an increase in risk of uterine cancer (adjusted hazard ratio [HR] = 1.2; 95% confidence interval [CI] = 0.94, 1.6), with some evidence of a dose–response for frequency of talc use (P-for-trend = 0.07). Ever douching was not associated with uterine cancer risk (HR = 1.0; 95% CI = 0.72, 1.5), with no evidence of a frequency dose–response (P = 0.96). The estimates were similar when we restricted to invasive endometrial cancers, but not when we further restricted to endometroid adenocarcinomas.

Conclusion:
The positive association we observed between talc use and uterine cancer risk is consistent with findings from previous prospective cohort studies of endometrial cancer. The relationships between uterine cancer and both douching and talc use merit further consideration, particularly as both exposures are preventable.
Inhibitors of the Janus Kinases
Authors: Antonelli Elisabetta , Torti Gabriele , Bassotti Gabrio 
Published: August 2019

Background:
The treatment of ulcerative colitis (UC) is based on conventional therapies (aminosalicylates, corticosteroids, and immunosuppressants) and when these are ineffective, biologic drugs. However, in a substantial portion of patients undergoing treatment with biologic agents there is primary or secondary loss of response. Thus, new therapeutic options are been actively explored; among these, there is interest in the Janus kinase (JAK) inhibitors, small molecules that can be administered orally.

Methods:
We carried out an extensive literature search concerning the effects of JAK inhibitors for the treatment of patients with UC.

Results:
Tofacitinib is the drug more extensively studied in this setting, and it was recently approved in Europe for the treatment of moderate to severe UC. The available data suggest that this drug can be effective in obtaining clinical and endoscopic remission in UC patients unresponsive to other treatments, even in those previously treated with biologic drugs. In addition, the drug was able to improve significantly the quality of life of these patients. There are still few data available for the treatment of UC with other JAK inhibitors.

Conclusions:
The JAK inhibitors, in particular tofacitinib, are a new class of orally administered drugs effective for the treatment of UC. However, more studies are needed to ascertain the safety of tofacitinib in the long term and whether other compounds of this class may be equally effective.
The Use of Capsule Endoscopy For Diagnosis of Iron Deficiency Anemia: A Retrospective Analysis
Authors: Stone James , Grover Kanika , Bernstein Charles N. 
Published: August 2019

Background:
There was some ambiguity in the recent guidelines on the use of capsule endoscopy (CE) in cases of iron deficiency anemia (IDA).

Goal:
We aimed to examine the yield of CE in diagnosing the cause of IDA and to define clinical parameters that predict higher diagnostic yields.

Materials and Methods:
A total of 1351 individuals underwent CE in Winnipeg between 2005 and 2016. All studies were reported by 1 reading physician. Data included demographics and requested information on medication use, prior imaging studies, and hemoglobin and ferritin levels. In a total of 620 (46%) patients, CE was indicated for occult gastrointestinal bleeding or IDA. Positive findings on CE were separated into “definite” and “possible.” Multinomial regression analysis was used to determine the variables correlated with definite CE findings. A survey analysis was then used to assess how the study results impacted further management.

Results:
With regard to the 620 patients, the mean age was 62.9 years, mean hemoglobin level was 89 g/L, and median ferritin level was 9 μg/L. A total of 210 (33.9%) patients had positive findings (definite: 23%, possible: 10.8%). Vascular ectasias were the majority of definite findings (47.5%). Predictors of definite findings were age (relative risk ratio: 1.04; 95% confidence interval: 1.02-1.06) and male sex (relative risk ratio: 1.88; 95% confidence interval: 1.25-2.83). An overall 12.7% of positive studies required therapeutic intervention, with 65.8% undergoing further workup.

Conclusion:
We report a 33.9% positive yield, with 65.8% of patients undergoing further workup as a result of CE and 12.7% requiring therapeutic intervention. We conclude that CE plays an important role in the investigation of IDA and occult gastrointestinal bleeding and has important implications on further management.
A rare cutaneous phototoxic rash after vandetanib therapy in a patient with thyroid cancer
Authors: Yin Yue , Qiu Xin Ye , Zhang Yan Hua , Zhang Bin 
Published: August 2019

Abstract

Rationale:
Vandetanib is effective for treating symptomatic or progressive medullary thyroid cancer (MTC) in patients with unresectable locally advanced or metastatic disease, but its toxicity such as photosensitivity reactions should be considered. It is a rare adverse effect of this drug but might cause severe morbidity and even mortality.

Patient concerns:
A 26-year man with MTC developed phototoxic rashes on the sun-exposed areas of his shin after 15 days from the initiation of vandetanib treatment. Grade II skin toxicity was evaluated based on the Common Terminology Criteria for Adverse Events standard.

Diagnoses:
Drug-induced phototoxic rash.

Interventions:
The vandetanib dose was reduced by 30%, and the application of topical steroids and sunscreen was adopted.

Outcomes:
After dose reduction of vandetanib, the symptoms of vandetanib-induced phototoxic rash resolved, although residual pigmentation was observed.

Lessons:
Close attention should be paid to the adverse effect of vandetanib, phototoxic rash, and patients should be advised on the prevention and treatment measures.
Effect of coronary collateral circulation on the prognosis of elderly patients with acute ST-segment elevation myocardial infarction treated with underwent primary percutaneous coronary intervention
Authors: Chu Ai-Ai , Li Wei , Zhu You-Qi , Meng Xiao-Xue , Liu Guo-Yong 
Published: August 2019

Abstract
Investigate the effect of coronary collateral circulation (CCC) on the prognosis of elderly patients with acute ST-segment elevation myocardial infarction (STEMI) and acute total occlusion (ATO) of a single epicardial coronary artery.
Three hundred forty-six advanced-age patients (age ≥60 years) with STEMI and ATO who underwent primary percutaneous coronary intervention (PCI) were enrolled in this study. According to the Rentrop grades, the patients were assigned to the poor CCC group (Rentrop grade 0–1) and good CCC group (Rentrop grade 2–3).
Multivariate logistic regression analysis revealed that poor coronary collateral circulation was an independent factor for Killip class ≥2 (odds ratio [OR]: –1.559; 95% confidence interval [CI]: 1.346–2.378; P = .013), the use of an intra-aortic balloon pump (IABP) (OR: –1.302; 95% CI: 0.092–0.805; P = .019), and myocardial blush grade (MBG) 3 (OR: 1.516; 95% CI: 2.148–9.655; P < .001). We completed a 12-month follow-up, during which 52 patients (15.0%) were lost to follow-up and 19 patients (5.5%) died. Univariate analysis (Kaplan–Meier and log-rank tests) suggested that poor CCC had a significant effect on all-cause mortality (P = .046), while multivariate analysis (Cox regression analysis) indicated that CCC had no statistically significant effect on all-cause mortality (P = .089) after the exclusion of other confounding factors. After excluding the influence of other confounding factors, this study showed that the mortality rate increased by 26.9% within 1 year for every 1-hour increment of time of onset. The mortality rate in patients with Killip class ≥2 was 8.287 times higher than that in patients with Killip class 0 to 1. The mortality rate in patients over 75 years was 8.25 times higher than that in patients aged 60 to 75 years. The mortality rate in patients with myocardial blush grade 3 (MBG 3) was 5.7% higher than that in patients with MBG 0–2.
The conditions of CCC in the acute phase had no significant direct effect on all-cause mortality in patients, but those with good CCC had a higher rate of MBG 3 after primary PCI and a lower rate of Killip ≥2.
Post-treatment alpha-fetoprotein response predicts prognosis of patients with hepatocellular carcinoma
Authors: He Chao , Peng Wei , Liu Xiaojuan , Li Chuan , Li Xueting , Wen Tian-Fu 
Published: August 2019

Abstract

Background:
Post-treatment alpha-fetoprotein (AFP) response has been reported to be associated with prognosis of hepatocellular carcinoma (HCC) patients, but the results were not consistent. This meta-analysis aimed to explore the relationship between AFP response and clinical outcomes of HCC.

Methods:
PubMed, Embase, Medline and Cochrane library were searched for relevant articles published before March 20, 2019. The data were analyzed using RevMan5.3 software.

Results:
Twenty-nine articles with 4726 HCC patients were finally included for analysis. The pooled results showed that post-treatment AFP response was significantly associated with overall survival (OS) (hazard ratio (HR) = 0.41, 95% confidence interval (CI): 0.35–0.47, P <.001), progression free survival (PFS) (HR = 0.46, 95% CI: 0.39–0.54, P <.001) and recurrence free survival (RFS) (HR = 0.41, 95% CI: 0.29–0.56, P <.001) of HCC patients.

Conclusion:
post-treatment AFP response might be a useful prognostic marker for HCC patients.
Poor response to rivaroxaban in nephrotic syndrome with acute deep vein thrombosis
Authors: Li Yan , Chen Yikuan , Qi Xiaotong , Hu Bangqin , Du Qingqing , Qian Yan 
Published: August 2019

Abstract

Rationale:
Hypercoagulability can lead to thromboembolic events that are a life-threatening complication of nephrotic syndrome (NS). Conventional anticoagulants are first-line treatment in the presence of demonstrated thrombosis in NS. Direct-acting oral anticoagulants (DOACs) have provided useful alternatives for the prevention and treatment of thromboembolic events.

Patient concerns:
A 59-year-old male developed lower limbs deep vein thrombosis (DVT) during the early course of NS but presented poor response to oral therapeutic doses of rivaroxaban. The decision was made to switch from rivaroxaban to heparin and subsequently bridged to warfarin. The patient presented significant clinical symptom improvement.

Diagnosis:
NS with Lower limbs DVT.

Interventions:
Rivaroxaban was discontinued and switch to heparin and subsequently bridged to warfarin.

Outcomes:
Venography result of both lower limb vein showed the venous wall was smooth without obvious stenosis or obstruction. Edema of the patient's lower limbs gradually improved and disappeared.

Lessons:
The existing published data on the application of DOACs in NS are limited. DOACs have an immediate anticoagulant effect and have demonstrated safety and efficacy and required no routine monitoring, however, application of these agents in NS likely requires further investigation before widespread adoption.
Dynamic change of depression and anxiety after chemotherapy among patients with ovarian cancer
Authors: Liu Hongxia , Yang Linqing 
Published: August 2019

Abstract
Psychological state of patients with ovarian cancer is worthy of attention. We aimed to investigate the levels of anxiety and depression in patients with ovarian cancer. We also investigated the dynamic changes in anxiety and depression levels after chemotherapy.
A total of 228 females were included in this study. Among them, a total of 111 participants had ovarian cancer and 117 females who underwent a physical examination were selected as healthy controls. All patients enrolled were asked to fill in the Self-rating Depression Scale and the Self-rating Anxiety Scale. For patients with ovarian cancer, repeat questionnaires were measured after cycle 1 chemotherapy.
The depression score of patients with ovarian cancer was 45.90 ± 10.19, significantly higher than in controls (36.08 ± 9.06, P < .001). Similar results were observed in respect of anxiety score. The score of ovarian cancer patients was 39.53 ± 12.92, significantly higher than of controls (32.15 ± 7.44, P < .001). Multivariate analyses were conducted, and the results showed that young age was the independent risk factor associated with depression among patients with ovarian cancer, while young age and singleness were the independent risk factors associated with anxiety. Repeat questionnaires were measured after chemotherapy. Interestingly, we found depression scores decreased from 45.90 ± 10.19 to 36.29 ± 8.98 after chemotherapy (P < .001), while anxiety score increased from 39.53 ± 12.92 to 42.75 ± 9.96 after chemotherapy (P = .009). Multivariate analysis suggested that only higher income and higher baseline depression score were the independent and most relevant risk factors associated with depression remission after chemotherapy. For patients with anxiety remission, only higher baseline anxiety score was the independent risk factor associated with anxiety remission.
This study suggests that for patients with ovarian cancer, timely monitoring of the patient's psychological state, especially before and after chemotherapy treatment, is very important. Assessing the changes in the patient's psychological state, screening the population with risk factors, and prompt intervention by mobilizing social support may be effective in preventing depression and anxiety in such population.
Recurrent anti-GBM disease with T-cell large granular lymphocytic leukemia
Authors: Zhang Min , Guan Nan , Zhu Ping , Chen Tong , Liu Shaojun , Hao Chuanming , Xue Jun 
Published: August 2019

Abstract

Rationale:
Anti-glomerular basement membrane disease (anti-GBM disease) is a rare small vessel vasculitis caused by autoantibodies directed against the glomerular and alveolar basement membranes. Anti-GBM disease is usually a monophasic illness and relapse is rare after effective treatment. This article reports a case of coexistence of recurrent anti-GBM disease and T-cell large granular lymphocytic (T-LGL) leukemia.

Patient concerns:
A 37-year-old man presented with hematuria, edema, and acute kidney injury for 2 months.

Diagnosis:
Anti-GBM disease was diagnosed by renal biopsy, in which crescentic glomerulonephritis was observed with light microscopy, strong linear immunofluorescent staining for immunoglobulin G on the GBM and positive serum anti-GBM antibody. Given this diagnosis, the patient was treated with plasmapheresis, steroids, and cyclophosphamide for 4 months. The anti-GBM antibody titer was maintained to negative level but the patient remained dialysis-dependent. One year later, the patient suffered with a relapse of anti-GBM disease, after an extensive examination, he was further diagnosed T-LGL leukemia by accident.

Interventions:
The patient received cyclosporine A therapy for T-LGL leukemia.

Outcomes:
After treatment with cyclosporine A, serum anti-GBM antibody became undetectable. During the 16 months follow-up, anti-GBM titer remained normal and abnormal T-lymphocytes in the bone marrow and peripheral blood were also decreased.

Lessons:
T-LGL leukemia is an indolent lymphoproliferative disorder that represents a monoclonal expansion of cytotoxic T cells, which has been reported to be accompanied by some autoimmune diseases. This is the first report of coincidence of T-LGL leukemia and anti-GBM disease, and suggests there are some relationships between these 2 diseases. Clinical physicians should exclude hematological tumors when faced with recurrent anti-GBM disease.
Endovascular treatment of pulmonary sequestration with thoracic endograft
Authors: Chen Yu , Liu Bao , Shao Jiang , Liu Duan , Zheng Yuehong 
Published: August 2019

Abstract

Introduction:
Pulmonary sequestration (PS) is a rare congenital lung malformation. The classical treatment of the disease has been conventional surgery with resection of abnormal parenchyma. Recently, the endovascular embolization has been proposed for the treatment of this disease. Here we present 2 cases of PS successfully treated with thoracic endograft.

Patient concerns:
Two patients with abnormal consolidation in the left lower lobe were admitted in our hospital.

Diagnosis:
Chest computed tomography angiography (CTA) showed abnormal consolidation in the left lower lobe, which received systemic blood supply from the descending aorta in both patients. So the diagnosis of PS was confirmed.

Interventions:
Endovascular treatment with thoracic endograft was successfully performed.

Outcomes:
The patients recovered well and were completely free of symptoms. And the CTA follow-up showed the abnormal pulmonary parenchyma shrunk significantly.

Conclusions:
Endovascular treatment with thoracic endograft is a promising treatment option for PS.