bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic variation implicates plasma angiopoietin-2 in the development of acute kidney injury sub-phenotypes
Authors: Bhatraju Pavan K. , Cohen Max , Nagao Ryan J. , Morrell Eric D. , Kosamo Susanna , Chai Xin-Ya , Nance Robin , Dmyterko Victoria , Delaney Joseph , Christie Jason D. , Liu Kathleen D. , Mikacenic Carmen , Gharib Sina A. , Liles W. Conrad , Zheng Ying , Christiani David C. , Himmelfarb Jonathan , Wurfel Mark M. 
Published: July 2020

Abstract
Background
We previously identified two acute kidney injury (AKI) sub-phenotypes (AKI-SP1 and AKI-SP2) with different risk of poor clinical outcomes and response to vasopressor therapy. Plasma biomarkers of endothelial dysfunction (tumor necrosis factor receptor-1, angiopoietin-1 and 2) differentiated the AKI sub-phenotypes. However, it is unknown whether these biomarkers are simply markers or causal mediators in the development of AKI sub-phenotypes.

Methods
We tested for associations between single-nucleotide polymorphisms within the Angiopoietin-1, Angiopoietin-2, and Tumor Necrosis Factor Receptor 1A genes and AKI- SP2 in 421 critically ill subjects of European ancestry. Top performing single-nucleotide polymorphisms (FDR < 0.05) were tested for cis-biomarker expression and whether genetic risk for AKI-SP2 is mediated through circulating biomarkers. We also completed in vitro studies using human kidney microvascular endothelial cells. Finally, we calculated the renal clearance of plasma biomarkers using 20 different timed urine collections.

Results
A genetic variant, rs2920656C > T, near ANGPT2 was associated with reduced risk of AKI-SP2 (odds ratio, 0.45; 95% CI, 0.31–0.66; adjusted FDR = 0.003) and decreased plasma angiopoietin-2 (p = 0.002). Causal inference analysis showed that for each minor allele (T) the risk of developing AKI-SP2 decreases by 16%. Plasma angiopoietin-2 mediated 41.5% of the rs2920656 related risk for AKI-SP2. Human kidney microvascular endothelial cells carrying the T allele of rs2920656 produced numerically lower levels of angiopoietin-2 although this was not statistically significant (p = 0.07). Finally, analyses demonstrated that angiopoietin-2 is minimally renally cleared in critically ill subjects.

Conclusion
Genetic mediation analysis provides supportive evidence that angiopoietin-2 plays a causal role in risk for AKI-SP2.
Nephrotic syndrome due to minimal-change disease superimposed on anti-glomerular basement membrane antibody positive glomerulonephritis; a case report
Authors: Shibata Yuko , Fukuoka Kazuhito , Yokota Riyo , Lee Heryon , Sayo Hikaru , Ikegaya Noriko , Mori Kiyotaka , Yamamoto Jin , Isomura Aya , Nagahama Kiyotaka , Shimoyamada Hiroaki , Kawakami Takahisa , Komagata Yoshinori , Kaname Shinya 
Published: July 2020

Abstract
Background
The prognosis for renal function in anti-GBM glomerulonephritis (anti-GBM GN) is extremely poor, and when renal impairment progresses severely, it is difficult to expect improvement. In addition, it is also known that once the disease activity can be controlled by aggressive treatment, its recurrence is rare. We experienced an anti-GBM GN that improved from severe renal dysfunction and relapsed. A possible cause was the superimpose of nephrotic syndrome due to minimal change disease (MCD).

Case presentation
A 30-year-old man was admitted to our hospital because of general malaise, fever, oliguria and renal dysfunction. The patient’s laboratory data showed serum creatinine as high as 6.6 mg/dl, and severe inflammation (C-reactive protein 20.6 mg/dl). Anti-glomerular basement membrane antibody (anti-GBM Ab) was detected in his serum, which led to the diagnosis of anti-GBM GN. Treatment was initiated with high-dose glucocorticoid (GC) and plasma exchange therapy (PE), and the patient’s renal function and oliguria improved rapidly and he was discharged 40 days after admission. Renal biopsy findings showed cellular crescents associated with linear IgG depositions along the glomerular tufts compatible with anti-GBM GN, but only about one-third of the glomeruli was involved, suggesting that it still remains an early stage of the disease. However, 2 months after discharge, he had a relapse and was readmitted due to severe proteinuria with positive anti-GBM Ab. On the second admission, after high-dose GC and PE combined with intravenous cyclophosphamide, and remission was achieved. Despite the relatively minor renal biopsy findings, the patient showed rapid renal dysfunction and relatively rapid improvement with our treatment. Electron microscopy of the renal biopsy tissue showed significant foot process effacement on podocytes in the apparently normal glomeruli, without electron dense deposits.

Conclusion
On the basis of clinical course and renal pathology, it is suggested that the present case was a rare complication of an early stage of anti-GBM GN and minimal change nephrotic syndrome. Although the simultaneous development of anti-GBM GN and MCD with anti-GBM antibody is unclear, it might have been precipitated by influenza infection or some unknown factor.
The prognosis of hepatoid adenocarcinoma of the stomach: a propensity score-based analysis
Authors: Zhou Kai , Wang Anqiang , Ao Sheng , Chen Jiahui , Ji Ke , He Qifei , Ji Xin , Wu Xiaojiang , Zhang Ji , Li Zhongwu , Bu Zhaode , Ji Jiafu 
Published: July 2020

Abstract
Background
To investigate whether there is a distinct difference in prognosis between hepatoid adenocarcinoma of the stomach (HAS) and non-hepatoid adenocarcinoma of the stomach (non-HAS) and whether HAS can benefit from radical surgery.

Methods
We retrospectively reviewed 722 patients with non-HAS and 75 patients with HAS who underwent radical gastrectomy between 3 November 2009 and 17 December 2018. Propensity score matching (PSM) analysis was used to eliminate the bias among the patients in our study. The relationships between gastric cancer type and overall survival (OS) were evaluated by the Kaplan-Meier method and Cox regression.

Results
Our data demonstrate that there was no statistically significant difference in the OS between HAS and non-HAS {K-M, P = log rank (Mantel-Cox), (before PSM P = 0.397); (1:1 PSM P = 0.345); (1:2 PSM P = 0.195)}. Moreover, there were no significant differences in the 1-, 2-, or 3-year survival rates between patients with non-HAS and patients with HAS (before propensity matching, after 1:1 propensity matching, and after 1:2 propensity matching).

Conclusion
HAS was generally considered to be an aggressive gastric neoplasm, but its prognosis may not be as unsatisfactory as previously believed.
Treatment patterns and health outcomes in metastatic renal cell carcinoma patients treated with targeted systemic therapies in the UK
Authors: Hawkins Robert , Fife Kate , Hurst Michael , Wang Meng , Naicker Niroshini , Nolasco Sarah , Eisen Tim , Matakidou Athena , Gordon Jason 
Published: July 2020

Abstract
Background
Patients with metastatic renal cell carcinoma (mRCC) treated with targeted systemic therapies have demonstrated favourable outcomes in randomised controlled trials, however real-world evidence is limited. Thus, this study aimed to determine the effectiveness of targeted systemic therapies for patients with mRCC in routine clinical practice in the UK.

Methods
A retrospective, observational, longitudinal study based on chart review of newly diagnosed adult mRCC patients treated at two UK hospitals from 2008 to 2015 was conducted. Targeted systemic therapies recommended for use in mRCC patients were evaluated across first to third lines of therapy (1LOT-3LOT). Important exclusions were treatment with cytokine therapy and within non-standard of care clinical trials. Primary outcome measure was overall survival (OS); data were analysed descriptively and using Kaplan-Meyer analysis.

Results
652 patients (65.3% male, 35.0% ≥70 years) were included. In 1LOT, 98.5% of patients received sunitinib or pazopanib. In 2LOT and 3LOT, 99.0 and 94.4% received axitinib or everolimus. Median OS was 12.9, 6.5 and 5.9 months at 1LOT, 2LOT and 3LOT respectively. Estimated OS at 1-year was 52.4% (95% CI: 48.6–56.4%) in 1LOT, 31.5% (25.2–39.5%) in 2LOT and 23.8% (10.1–55.9%) in 3LOT. Median OS from 1LOT in favourable, intermediate and poor MSKCC were 39.7, 15.8 and 6.1 months respectively.

Conclusions
In this study, treatment was consistent with current National Institute for Health and Care Excellence (NICE) guidelines for mRCC patients. Although the study population favoured poorer prognosis patients, outcomes were more favourable than those for England at the same time. However, overall survival in this ‘real-world’ population remains poor and indicates significant unmet need for effective and safe treatment options to improve survival among mRCC patients.
Short-term outcomes of robotic- versus laparoscopic-assisted Total Gastrectomy for advanced gastric Cancer: a propensity score matching study
Authors: Yang Changdong , Shi Yan , Xie Shaohui , Chen Jun , Zhao Yongliang , Qian Feng , Hao Yingxue , Tang Bo , Yu Peiwu 
Published: July 2020

Abstract
Background
Few studies have been designed to evaluate the short-term outcomes between robotic-assisted total gastrectomy (RATG) and laparoscopy-assisted total gastrectomy (LATG) for advanced gastric cancer (AGC). The purpose of this study was to assess the short-term outcomes of RATG compared with LATG for AGC.

Methods
We retrospectively evaluated 126 and 257 patients who underwent RATG or LATG, respectively. In addition, we performed propensity score matching (PSM) analysis between RATG and LATG for clinicopathological characteristics to reduce bias and compared short-term surgical outcomes.

Results
After PSM, the RATG group had a longer mean operation time (291.14 ± 59.18 vs. 270.34 ± 52.22 min, p = 0.003), less intraoperative bleeding (154.37 ± 89.68 vs. 183.77 ± 95.39 ml, p = 0.004) and more N2 tier RLNs (9.07 ± 5.34 vs. 7.56 ± 4.50, p = 0.016) than the LATG group. Additionally, the total RLNs of the RATG group were almost significantly different compared to that of the LATG group (34.90 ± 13.05 vs. 31.91 ± 12.46, p = 0.065). Moreover, no significant differences were found between the two groups in terms of the length of incision, proximal resection margin, distal resection margin, residual disease and postoperative hospital stay. There was no significant difference in the overall complication rate between the RATG and LATG groups after PSM (23.8% vs. 28.6%, p = 0.390). Grade II complications accounted for most of the complications in the two cohorts after PSM. The conversion rates were 4.55 and 8.54% in the RATG and LATG groups, respectively, with no significant difference (p = 0.145), and the ratio of splenectomy were 1.59 and 0.39% (p = 0.253). The mortality rates were 0.8 and 0.4% for the RATG and LATG groups, respectively (p = 1.000).

Conclusion
This study demonstrates that RATG is comparable to LATG in terms of short-term surgical outcomes.
Anti-vascular endothelial growth factor in neovascular age-related macular degeneration – a systematic review of the impact of anti-VEGF on patient outcomes and healthcare systems
Authors: Finger Robert P. , Daien Vincent , Eldem Bora M. , Talks James S. , Korobelnik Jean-Francois , Mitchell Paul , Sakamoto Taiji , Wong Tien Yin , Pantiri Krystallia , Carrasco Joao 
Published: July 2020

Abstract
Background
Systematically review the evidence describing the impact of anti–vascular endothelial growth factor (anti-VEGF) therapy on neovascular age-related macular degeneration (nAMD) patient outcomes and healthcare resource utilization.

Methods
A systematic literature review was completed using Medline and EMBASE for publications prior to July 2018, and proceedings from major ophthalmology conferences (January 2016 to July 2018). The search strategy combined terms for nAMD with terms for anti-VEGF and study design. The review focused on publications describing the impact of anti-VEGF on blindness, visual impairment, vision-related quality of life (VRQoL), mortality, and costs. The search targeted data collected in epidemiological or observational studies to reflect real-world outcomes but also considered modeling-based approaches.

Results
The use of anti-VEGF in clinical practice was associated with significant reduction in the incidence of blindness by nAMD. Population-based analyses reported reduction in incidence among the general population of 47% (9.1 cases/100,000 in 2006 to 4.8 cases/100,000 in 2011). Among patients aged ≥50 years, a reduction of 50% was observed (52.2 cases/100,000 in 2000 to 25.7 cases/100,000 in 2010). In some cases, the odds of decreased vision (defined as decline from normal to moderate, moderate to severe, or severe to blindness) fell by 41% following introduction of anti-VEGF. Patients’ VRQoL improved with treatment, with patients reporting a positive impact shortly after treatment was initiated. Change on National Eye Institute 25-Item Visual Function Questionnaire score from baseline to month 12 ranged from 0.7 to 4.4. Although nAMD patients report signs of depression and anxiety, the evidence suggests that there is no association between the use of anti-VEGF and the prevalence or diagnosis of depression. The introduction of anti-VEGF led to increased overall treatment costs due to replacement of existing less frequently administered treatments (e.g. photodynamic therapy) and increased number of patients treated (prior to anti-VEGF, only ~ 20% of patients were eligible for treatment).

Conclusions
The introduction of anti-VEGF agents has been associated with a positive impact on patient-relevant outcomes, including a significant reduction in incidence of blindness and visual impairment by nAMD. Anti-VEGF agents replaced less-effective treatments, improving patient outcomes and broadening the patient population eligible for treatment.
Barriers to access to outpatient mental health care for refugees and asylum seekers in Switzerland: the therapist’s view
Authors: Kiselev Nikolai , Morina Naser , Schick Matthis , Watzke Birgit , Schnyder Ulrich , Pfaltz Monique C. 
Published: July 2020

Abstract
Background
More than 120,000 refugees and asylum seekers are currently living in Switzerland. The prevalence of mental disorders among this population is significantly higher than that in the general population. While effective treatment options and cross-cultural, specialized treatment centers exist, they tend to be overloaded by their target populations. General outpatient primary health care providers might be able to compensate for the lack of specialized treatment slots. To date, however, it is unknown how often and under what conditions (e.g., length of waiting lists) refugees and asylum seekers are treated outside of specialized centers and whether there are barriers that prevent providers in outpatient settings from treating more patients in this subgroup. The present study aimed to assess the challenges and barriers faced by psychiatrists and psychotherapists working in outpatient settings in Switzerland in treating refugees and asylum seekers to determine the potential capacity of this group to provide mental health care.

Methods
An online survey was conducted during the winter of 2017/2018. The survey was constructed in three official languages and took 10–15 min to complete. Spearman’s correlations, Mann-Whitney U-Tests, and Chi-squared tests were conducted to analyze the data.

Results
Eight hundred and sixty-seven (N = 867) psychotherapists and psychiatrists working in outpatient settings completed the survey: 43% of them reported having treated between 1 and 9 refugees or asylum seekers in the past 12 months, and a further 13% reported treating 10 or more. Interpreters were used for almost every other patient with a refugee or asylum-seeker background. At the same time, the funding of interpreters, as well as the funding of treatment in general, were reported to be the biggest hurdles to treating more refugees and asylum seekers.

Conclusions
Given the low number of patients rejected for capacity reasons (between 2 and 5%) and the median waiting times for the admission of new patients ranging between 2 and 3 weeks, outpatient primary mental health care providers might treat more refugees and asylum seekers and relieve specialized treatment centers. However, barriers such as lack of funding of interpreters seem to hinder them. Appropriate steps by the authorities are needed to improve the current situation.
Patient and health system delay among TB patients in Ethiopia: Nationwide mixed method cross-sectional study
Authors: Datiko Daniel G. , Jerene Degu , Suarez Pedro 
Published: July 2020

Abstract
Background
Effective tuberculosis (TB) control is the end result of improved health seeking by the community and timely provision of quality TB services by the health system. Rapid expansion of health services to the peripheries has improved access to the community. However, high cost of seeking care, stigma related TB, low index of suspicion by health care workers and lack of patient centered care in health facilities contribute to delays in access to timely care that result in delay in seeking care and hence increase TB transmission, morbidity and mortality. We aimed to measure patient and health system delay among TB patients in Ethiopia.

Methods
This is mixed method cross-sectional study conducted in seven regions and two city administrations. We used multistage cluster sampling to randomly select 40 health centers and interviewed 21 TB patients per health center. We also conducted qualitative interviews to understand the reasons for delay.

Results
Of the total 844 TB patients enrolled, 57.8% were men. The mean (SD) age was 34 (SD + 13.8) years. 46.9% of the TB patients were the heads of household, 51.4% were married, 24.1% were farmers and 34.7% were illiterate. The median (IQR) patient, diagnostic and treatment initiation delays were 21 (10–45), 4 (2–10) and 2 (1–3) days respectively. The median (IQR) of total delay was 33 (19–67) days; 72.3% (595) of the patients started treatment after 21 days of the onset of the first symptom. Poverty, cost of seeking care, protracted diagnostic and treatment initiation, inadequate community based TB care and lack of awareness were associated with delay. Community health workers reported that lack of awareness and the expectation that symptoms would resolve by themselves were the main reasons for delay.

Conclusion
TB patients’ delay in seeking care remains a challenge due to limited community interventions, cost of seeking care, prolonged diagnostics and treatment initiation. Therefore, targeted community awareness creation, cost reduction strategies and improving diagnostic capacity are vital to reduce delay in seeking TB care in Ethiopia.
The quality of drinking and domestic water from the surface water sources (lakes, rivers, irrigation canals and ponds) and springs in cholera prone communities of Uganda: an analysis of vital physicochemical parameters
Authors: Bwire Godfrey , Sack David A. , Kagirita Atek , Obala Tonny , Debes Amanda K. , Ram Malathi , Komakech Henry , George Christine Marie , Orach Christopher Garimoi 
Published: July 2020

Abstract
Background
Water is the most abundant resource on earth, however water scarcity affects more than 40% of people worldwide. Access to safe drinking water is a basic human right and is a United Nations Sustainable Development Goal (SDG) 6. Globally, waterborne diseases such as cholera are responsible for over two million deaths annually. Cholera is a major cause of ill-health in Africa and Uganda. This study aimed to determine the physicochemical characteristics of the surface and spring water in cholera endemic communities of Uganda in order to promote access to safe drinking water.

Methods
A longitudinal study was carried out between February 2015 and January 2016 in cholera prone communities of Uganda. Surface and spring water used for domestic purposes including drinking from 27 sites (lakes, rivers, irrigation canal, springs and ponds) were tested monthly to determine the vital physicochemical parameters, namely pH, temperature, dissolved oxygen, conductivity and turbidity.

Results
Overall, 318 water samples were tested. Twenty-six percent (36/135) of the tested samples had mean test results that were outside the World Health Organization (WHO) recommended drinking water range. All sites (100%, 27/27) had mean water turbidity values greater than the WHO drinking water recommended standards and the temperature of above 17 °C. In addition, 27% (3/11) of the lake sites and 2/5 of the ponds had pH and dissolved oxygen respectively outside the WHO recommended range of 6.5–8.5 for pH and less than 5 mg/L for dissolved oxygen. These physicochemical conditions were ideal for survival of Vibrio. cholerae.

Conclusions
This study showed that surface water and springs in the study area were unsafe for drinking and had favourable physicochemical parameters for propagation of waterborne diseases including cholera. Therefore, for Uganda to attain the SDG 6 targets and to eliminate cholera by 2030, more efforts are needed to promote access to safe drinking water. Also, since this study only established the vital water physicochemical parameters, further studies are recommended to determine the other water physicochemical parameters such as the nitrates and copper. Studies are also needed to establish the causal-effect relationship between V. cholerae and the physicochemical parameters.
Combined signaling of NF-kappaB and IL-17 contributes to Mesenchymal stem cells-mediated protection for Paraquat-induced acute lung injury
Authors: Zhang Lichun , Wang Yu , Shen Haitao , Zhao Min 
Published: July 2020

Abstract
Background
Paraquat (PQ) is an herbicide widely used in the world. PQ can cause pulmonary toxicity and even acute lung injury. Treatment for PQ poisoning in a timely manner is still a challenge for clinicians. Mesenchymal stem cell (MSC) transplantation has hold potentials for the treatment of several lung diseases including PQ poisoning. The aim of this study is to examine the mechanisms mediated by MSC transplantation to protect PQ-induced lung injury.

Methods
Here we performed the whole genome sequencing and compared the genes and pathways in the lung that were altered by PQ or PQ together with MSC treatment.

Results
The comparison in transcriptome identified a combined mitigation in NF-kappaB signaling and IL-17 signaling in MSC transplanted samples.

Conclusion
This study not only reiterates the important role of NF-kappaB signaling and IL-17 signaling in the pathogenesis of PQ-induced toxicity, but also provides insight into a molecular basis of MSC administration for the treatment of PQ-induced toxicity.