bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cumulative Antibiotic Use Significantly Decreases Efficacy of Checkpoint Inhibitors in Patients with Advanced Cancer
Authors: Tinsley Nadina , Zhou Cong , Tan Grace , Rack Samuel , Lorigan Paul , Blackhall Fiona , Krebs Matthew , Carter Louise , Thistlethwaite Fiona , Graham Donna , Cook Natalie 
Published: July 2019

Abstract

Background
With the advent of immunotherapy, substantial progress has been made in improving outcomes for patients with advanced cancer. However, not all patients benefit equally from treatment, and confounding immune-related issues may have an impact. Several studies suggest that antibiotic use (which alters the gut microbiome) may result in poorer outcomes for patients treated with immune checkpoint inhibitors (ICI).

Materials and Methods
This is a large, single-site retrospective review of n = 291 patients with advanced cancer treated with ICI (n = 179 melanoma, n = 64 non-small cell lung cancer, and n = 48 renal cell carcinoma). Antibiotic use (both single and multiple courses/prolonged use) during the periods 2 weeks before and 6 weeks after ICI treatment was investigated.

Results
Within this cohort, 92 patients (32%) received antibiotics. Patients who did not require antibiotics had the longest median progression-free survival (PFS), of 6.3 months, and longest median overall survival (OS), of 21.7 months. With other clinically relevant factors controlled, patients who received a single course of antibiotics had a shorter median OS (median OS, 17.7 months; p = .294), and patients who received multiple courses or prolonged antibiotic treatment had the worst outcomes overall (median OS, 6.3 months; p = .009). Progression-free survival times were similarly affected.

Conclusion
This large, multivariate analysis demonstrated that antibiotic use is an independent negative predictor of PFS and OS in patients with advanced cancer treated with ICIs. This study highlighted worse treatment outcomes from patients with cumulative (multiple or prolonged courses) antibiotic use, which warrants further investigation and may subsequently inform clinical practice guidelines advocating careful use of antibiotics.
Combined Microsatellite Instability and Elevated Microsatellite Alterations at Selected Tetranucleotide Repeats (EMAST) Might Be a More Promising Immune Biomarker in Colorectal Cancer
Authors: Chen Ming-Huang , Chang Shih-Ching , Lin Pei-Ching , Yang Shung-Haur , Lin Chun-Chi , Lan Yuan-Tzu , Lin Hung-Hsin , Lin Chien-Hsing , Lai Jiun-I , Liang Wen-Yi , Lu Meng-Lun , Yang Muh-Hwa , Chao Yee 
Published: July 2019

Abstract

Background
The form of microsatellite instability (MSI) affecting tetranucleotide repeats known as elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) has emerged as a new potential biomarker in multiple cancers. In colorectal cancer (CRC), the correlation between EMAST and MSI mutations remain inconclusive.

Materials and Methods
We evaluated 1,505 patients with CRC using five EMAST markers (D20S82, D20S85, D8S321, D9S242, and MYCL1) and the Bethesda panel of MSI markers. Most commonly, mutations involved in CRCs were identified by MassArray Assay, and DNA repair genes were analyzed by next-generation sequencing. Clinical characteristics and prognostic relevance were correlated with EMAST and MSI.

Results
Tumors that were EMAST positive and MSI high (MSI-H) were detected in 159 (10.6%) and 154 (10.2%) of 1,505 patients with CRC. Patients were divided into four groups according to EMAST and MSI status (EMAST-positive and MSI-H, EMAST-positive and microsatellite-stable [MSS], EMAST-negative and MSI-H, and EMAST-negative and MSS). The EMAST-positive and MSI-H group was associated with female predominance, higher prevalence of proximal colon tumors, early stage tumors, poorly differentiated tumors, mucinous histology, and higher incidence of mutations in PI3KCA, BRAF, TGFBR, PTEN, and AKT1 compared with other groups. Furthermore, compared with only EMAST-positive tumors or only MSI-H tumors, tumors that were both EMAST-positive and MSI-H had a higher frequency of MLH1, MSH3, MSH6, PMS2, and EXO1 gene mutations. Finally, the presence of EMAST-positive and MSI-H tumors was a good prognostic indicator in CRC.

Conclusion
High mutations in several DNA repair genes in EMAST-positive and MSI-H tumors suggest that this subtype of CRC might be more suitable for treatment with immune therapy.

Implications for Practice
Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) is a unique molecular subtype of colorectal cancer (CRC). The current study demonstrated that the EMAST-positive and MSI-high (MSI-H) group was associated with female predominance, higher prevalence of proximal colon tumors, early stage tumors, poorly differentiated tumors, mucinous histology, and higher incidence of mutations in PI3KCA, BRAF, TGFBR, PTEN, and AKT1 compared with other groups. Most importantly, high mutations in DNA repair genes and MSI-related genes in EMAST-positive and MSI-H tumors suggest that this subtype of CRC might be more suitable for treatment with immune therapy compared with MSI-H tumors alone.
Evaluating Glomerular Filtration Rate Slope as a Surrogate End Point for ESKD in Clinical Trials: An Individual Participant Meta-Analysis of Observational Data
Authors: Grams Morgan E. , Sang Yingying , Ballew Shoshana H. , Matsushita Kunihiro , Astor Brad C. , Carrero Juan Jesus , Chang Alex R. , Inker Lesley A. , Kenealy Timothy , Kovesdy Csaba P. , Lee Brian J. , Levin Adeera , Naimark David , Pena Michelle J. , Schold Jesse D. , Shalev Varda , Wetzels Jack F. M. , Woodward Mark , Gansevoort Ron T. , Levey Andrew S. , Coresh Josef 
Published: July 2019

Significance Statement
Randomized clinical trials of treatments to slow CKD progression often require large sample sizes and long follow-up to understand their effects on clinical events. This is especially true in patients with earlier stages of kidney disease who are unlikely to experience ESKD for many years. Surrogate study end points that occur earlier during disease progression could help. To evaluate whether eGFR decline over time may be a good surrogate end point, the authors did a meta-analysis of 14 cohorts. They found that slower eGFR decline was significantly associated with lower risk of ESKD in all populations, including those with better kidney function. The results suggest that change in the slope of eGFR decline may be a good surrogate end point for ESKD in clinical trials, particularly in longer trials with patients with rapidly progressive disease.

Background
Decline in eGFR is a biologically plausible surrogate end point for the progression of CKD in clinical trials. However, it must first be tested to ensure strong associations with clinical outcomes in diverse populations, including patients with higher eGFR.

Methods
To investigate the association between 1-, 2-, and 3-year changes in eGFR (slope) with clinical outcomes over the long term, we conducted a random effects meta-analysis of 3,758,551 participants with baseline eGFR≥60 ml/min per 1.73 m2 and 122,664 participants with eGFR<60 ml/min per 1.73 m2 from 14 cohorts followed for an average of 4.2 years.

Results
Slower eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years was associated with lower risk of ESKD in participants with baseline eGFR≥60 ml/min per 1.73 m2 (adjusted hazard ratio, 0.70; 95% CI, 0.68 to 0.72) and eGFR<60 ml/min per 1.73 m2 (0.71; 95% CI, 0.68 to 0.74). The relationship was stronger with 3-year slope. For a rapidly progressing population with predicted 5-year risk of ESKD of 8.3%, an intervention that reduced eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years would reduce the ESKD risk by 1.6%. For a hypothetical low-risk population with a predicted 5-year ESKD risk of 0.58%, the same intervention would reduce the risk by only 0.13%.

Conclusions
Slower decline in eGFR was associated with lower risk of subsequent ESKD, even in participants with eGFR≥60 ml/min per 1.73 m2, but those with the highest risk would be expected to benefit the most.
PERFIL EPIDEMIOLÓGICO DOS CASOS DE DENGUE NOTIFICADOS EM CERES–GOIÁS, DE 2014 A 2015
Authors: Guedes Deise Aparecida de Melo Oliveira , Rocha Benigno Alberto Moraes da 
Published: July 2019

Justificativa e Objetivos:A descrição do perfil epidemiológico é uma ferramenta importante na busca por soluções eficazes no que diz
respeito, em especial, às doenças infecciosas e às alternativas de melhoria da saúde pública, sendo instrumento para o desenvolvimento
de políticas adequadas às realidades locais. O presente artigo objetiva descrever o perfil epidemiológico dos casos de dengue notificados
à Secretaria Municipal de Saúde (SMS) de Ceres-GO nos anos de 2014 e 2015. Métodos: Trata-se de um estudo observacional descritivo
de corte transversal, desenvolvido através de pesquisa e interpretação de dados do Sistema de Notificação Compulsória de dengue. As
informações coletadas foram digitadas em um banco de dados, onde os tipos de distribuição de cada variável (quantitativas e qualitativas)
foram avaliados e distribuídos em forma de tabelas, sendo realizado cálculo das taxas de incidência por 100 mil habitantes. As variáveis
estudadas incluíram dados sociodemográficos e dados laboratoriais, coletados no período de março a maio de 2017. Resultados:Durante
os anos de 2014 e 2015 foram notificados um total de 3.374 possíveis casos de dengue no município de Ceres-GO, sendo destes, 189
referentes a 2014 e 3.185 a 2015, onde a taxa de incidência por 100 mil habitantes foi de 868 e 14.537, respectivamente. Comparando-se os
registros dos respectivos anos, observa-se que houve um aumento significativo de notificações, representando um crescimento 16 vezes
maior de um ano para o outro. Conclusão:Diversos aspectos evidenciam a gravidade da dengue, já que a inadequação de diversos fatores
contribui para o maior acometimento populacional. O manejo inadequado e o gerenciamento ineficaz de casos resultam no progresso da
doença, levando à sua rápida evolução e resultando muitas vezes em óbito.
Descritores:Dengue. Perfil de saúde. Saúde pública. Notificação compulsória
A segurança do paciente no contexto das flebites notificadas em um hospital universitário
Authors: Pereira Mariana Santana Rosário , Cunha Viviane Viana de Oliveira , Borghardt Andressa Tomazini , Lima Eliane De Fátima Almeida , Santos Tayana Fátima Ferreira , Portugal Flávia Batista 
Published: July 2019

Justificativa e Objetivos:A flebite pode levar à necessidade de intervenções assistenciais de maior complexidade, como a utilização de
antibioticoterapia ou até uma intervenção cirúrgica, além de prolongar a internação do paciente e aumentar o custo e risco de infecções.
O presente estudo visa descrever as flebites notificadas em um hospital universitário e assim contribuir com possíveis ações de melhoria
na qualidade do cuidado e na segurança do paciente. Métodos:Estudo observacional de caráter retrospectivo desenvolvido em três
unidades de internação de um hospital universitário do município de Vitória, ES, Brasil. No período de junho a agosto de 2017 foram
analisados os prontuários de 76 pacientes, a partir das notificações de flebite registradas por um software eletrônico. Também foram
coletadas informações sobre as condições sociodemográficas e clínicas dos pacientes e as relacionadas aos registros de enfermagem.
Os dados foram tabulados em planilha do Microsoft Office Excel2007 e analisados pelo programa de estatísticaStatistical Package for
the Social Sciences 22(SPSS 22). Resultados: Identificou-se que 56,4% das flebites ocorreram em homens, faixa etária entre 41 e 65 anos
(42,3%) e 46,1% dos pacientes fizeram uso de antibióticos. Houve registro da conduta adotada em 59,2% dos casos, e as mais realizadas
foram compressas de gelo (44,7%) e elevação do membro (34,2%). Conclusão:O conhecimento acerca das características das flebites
notificadas propicia o entendimento e a minimização deste evento adverso, a fim de estabelecer as condutas de prevenção e diminuição
do risco e da incidência.
Descritores:Flebite. Segurança do Paciente. Cateterismo Periférico. Cuidados de Enfermagem
Pengaruh Kedisiplinan Belajar Terhadap Hasil Belajar Mahasiswa dalam Mata Kuliah Konsep Dasar IPS
Authors: Kristin Firosalia , Kencana Sari Fransiska 
Published: July 2019

Penelitian ini bertujuan mengetahui pengaruh kedisiplinan belajar terhadap hasil belajar mahasiswa dalam mata kuliah konsep dasar IPS. Jenis penelitian ini adalah penelitian asosiatif dengan desain expost facto. Subjek penelitian adalah 60 mahasiswa PGSD UKSW angkatan 2017. Pengumpulan data dilakukan melalui angket dan tes. Anaisis data dilakukan dengan teknik uji regresi linier yang mencakup uji t dan pengukuran koefisien determinasi. Hasil penelitian menunjukkan 1) Nilai t hitung 2,904 > nilai t tabel 1,999, maknanya terdapat pengaruh kedisiplinan belajar teradap hasil belajar Konsep Dasar IPS Mahasiswa; 2) Nilai R Square sebesar 0,127, dengan arti bahwa pengaruh variabel kedisiplinan belajar terhadap variabel hasil belajar Konsep Dasar IPS Mahasiswa adalah 12,7%. Simpulannya melalui uji t menunjukkan adanya pengaruh kedisiplinan tergadap hasi belajar mahasiswa dalam mata kuliah Konsep Dasar IPS dengan pengaruh sebesar 12,7% yang ditunjukkan melaui hasil pengukuran koefisien determinasi.
Evaluation of quality of life of patients after surgical treatment of kidney cancer
Authors: Popov S. V. , Guseynov R. G. , Orlov I. N. , Skryabin O. N. , Davydov A. V. , Barkhitdinov R. S. , Katunin A. S. , Mirzabekov M/ M. 
Published: July 2019

Background. Restoring the quality of life of patients to a level comparable to that of practically healthy people is the most important task of medicine in general. At this stage of development of science, the main goal in the treatment of malignant diseases remains the preservation of life. However, now in oncological practice, methods whose potential allows not only to preserve life as such, but also to ensure the high quality of this life in all its manifestations, are acquiring greater and greater significance.The objective of the study is to compare the quality of life of persons with localized kidney cancer in the early and late periods after surgical treatment by radical nephroectomy and laparoscopic resection of renal tissue.Materials and methods. A questionnaire survey using SF-36 (Short Form-36), designed for a comprehensive assessment of the quality of life associated with health.Results. The quality of life of patients with localized kidney cancer before treatment is reduced due to a number of physical and mental nature, limiting labor, domestic and social activity and causing a feeling of dissatisfaction with their lives in general. These problems are disorders of physical, social and emotional functioning, physical pain, deterioration of general and mental health, limitations of role functioning due to physical and emotional state. After surgical treatment with laparoscopic resection, complete satisfaction of patients with the quality of their life was achieved during the first 1–3 postoperative months; after radical nephroectomy – not earlier than 1–3 years.Conclusion. One of the advantages of laparoscopic resection over radical nephroectomy is a higher quality of life of patients in the early and late periods after the intervention.
The validation results for APhiGT algorithm for clarification of prostate cancer staging before treatment (first step)
Authors: Sergeeva N. S. , Skachkova T. E. , Marshutina N. V. , Nushko K. M. , Shevchuk I. M. , Nazirov M. R. , Pirogov S. A. , Yurkov E. F. , Gitis V. G. , Alekseev B. Ya. , Kaprin A. D. 
Published: July 2019

Background. We have previously described an algorithm APhiGT (Age, Prostate Health index, Gleason score, TNM stage) for staging of prostate cancer (PC) before treatment. The algorithm was developed by logistic regression on an educational selection (ES) of 337 PC cases. The algorithm includes data about the age of patients, the levels of total prostate-specific antigen (PSA), free PSA, [-2]proPSA and the ranked data of the Gleason score (by biopsy results) and T (by TNM).Objective. Validation of APhiGT on the validation selection (VS) of 83 PC cases was carried out in this work.Materials and methods. ROC analysis was performed in ES and VS.Results and сonclusion. It is established that area under the curve (AUC), characterizing the ability to divide clinically significant subgroups of patients (Gleason score <7 vs. Gleason score ≥7, рТ2 vs. рТ3, localized indolent PC vs. localized aggressive PC) for APhiGT both in ES and VS was significantly higher than AUC for total PSA, %[-2]proPSA in free PSA and prostate health index. At the same time, in all clinical subgroups of patients AUC for VS was lower than AUC for ES, which may be due to a significantly smaller size of VS compared to ES.
Modern drug therapy of prostate cancer through the example of Moscow
Authors: Polyakova K. I. , Fisun A. G. , Govorov A. V. , Krysanova V. S. , Andreev D. A. , Ermolaeva T. N. , Andreyashkina I. I. , Zavyalov A. A. , Davydovskaya M. V. , Kokushkin K. A. 
Published: July 2019

Background. The average annual increment (5,09 %) of the prostate cancer (PC) incidence was highest across male oncological diseases registered in Russia from 2007 to 2017. 4643 new cases of PC were diagnosed in Moscow in 2017. As of 1st January 2018, the total number of living males with PC registered within Moscow healthcare system was 31,567.The study objective was to obtain the structure of factual costs related to medicine therapy of PC covered by the budget funds of the Moscow Healthcare Department in 2016–2017, that would help to further improve the system of subsidized drug provision for Moscow residents.Materials and methods. Using data from the information database of the Center for Medicine Provision of the Moscow City Department of Healthcare the following parameters were determined: total sum of expenses on drug purchase, mean treatment cost per 1 patient, number of patients receiving therapy, number of prescriptions, number of prescribed drug packs, mean pack cost, and others. The analyzed medicines were classified based on pharmacological and clinical groups. Costs for each class of therapies were studied.Results. During studied period (2016–2017), the most funds in Moscow were spent on abiraterone and goserelin. In 2016–2017, the amounts of prescribed packs were highest for androgen deprivation therapy: luteinizing hormone-releasing hormone agonists – goserelin and buserelin. In the group comprising 10 therapeutic regimens associated with highest costs, the percentages of costs for hormonal therapy and chemotherapy were respectively as following: 80 % and 16 % in 2016 and 75 % and 23 % in 2017. In the simplified model of costs associated with androgen deprivation therapy and treatment of metastatic castration-resistant PC without consideration of androgen deprivation therapy constituted 39 % and 61 % in 2016 and 36 % and 64 % in 2017. In the population of patients with prostate cancer, zoledronic acid, abiraterone, docetaxel, cabazitaxel were the most used medications in 2017 and the rate of enzalutamide usage was lowest.Conclusion. The highest costs are associated with treatment of metastatic castration-resistant PC. There is a growing necessity for improvement of funds spending on medications for patients with castration-resistant PC. This improvement could be achieved through development of medical methodologies that facilitate the selection of the most cost-effective approaches for early diagnosis and treatment.
Analisis Kestabilan Model Mangsa Pemangsa dengan Pemanenan Ambang Batas pada Populasi Pemangsa
Authors: Yusrianto Yusrianto , Toaha Syamsuddin , Kasbawati Kasbawati 
Published: July 2019

Abstrak Penelitian ini mengkaji model satu mangsa dan satu pemangsa yang saling berkompetisi. Fungsi predasi dari pemangsa diasumsikan menggunakan fungs1 respon Holling tipe II. Dengan asumsi bahwa adanya kompetisi intraspesifik pada popuasi pemangsa serta dilakukan pemanenan ambang batas pada popuasi pemangsa. Pada model tersebut dilakukan analisis tentang syarat kewujudan dan kestabilan titik keseimbangan interior. Analisis kestabilan titik keseimbangan interior dilakukan dengan metode linearisasi dan dengan memperhatikan nilai eigen dari matriks Jacobi yang diperoleh. Terdapat sepuluh titik kesetimbangan yang diperoleh pada model, satu diantaranya dapat dinterpretasikan. Titik tersebut dinyatakan stabil asimtotik. Berdasarkan hasil anasis menggunakan beberapa parameter, diketahui bahwa ada suatu waktu pemanenan ambang batas harus dihentikan karna sudah tidak memenuhi syarat kriteria ambang batas yang telah ditentukan.Kata kunci : Model mangsa pemangsa, Pemanenan ambang batas, Titik kesetimbanganAbstract This study examines the model of one prey and one predator who mutates each other. The predation function of predators is assumed to use the Holling type II response function. Assuming that the existence of intraspecific competition in predatory population and theshold harvesting for predatory population is carried out. In this model, an analysis of the actual conditions and stability of the interior balance point is carried out. Analysis of the interior stability balance points was carried out by linearization method and by taking into account the eigenvalues of the Jacobian matrix obtained. There are ten equilibrium points of engagement obtained on the model, one of which can be interpreted. This point is stated as asymptotically stable. Based on the results of analysis using several parameters, it is known that there is a time when harvesting the threshold must be stopped because it has not fulfill the specified criteria for threshold.Keyword : Prey-predator model threshold harvesting, equibrium point
DISKURSUS TAX AMNESTY MELALUI RUU PENGAMPUNAN NASIONAL (Potencial Fraud and Money Laundering Perspective)
Authors: Seputro Hanif Yusuf , Aneswari Yuyung Rizka , Darmayasa I. Nyoman 
Published: July 2019

Objective of this study is to explore discourse and issues on tax amnesty, and give several feedbacks for improvement of implementation of tax amnesty. This study employs descriptive method. First finding of this study signify that the tax amnesty becomes one of options of the central government to achieve target of tax sector. Second, Indonesia should learn from failure and success on implementation of tax amnesty in the prior period. Third, RUU (draft of law) of national amnesty must be clear. The amnesty is specific for tax. Hence, there will be no possibility to do corruption (TIPIKOR), or even money laundry that use to be done after the corruption (TIPIKOR) is occurred. Fourth, implementation of the tax amnesty programme should be followed by supporting policies, such as law of (UU) banking confidentiality and so on. Fifth, tax amnesty is a policy that is expected by many parties to fix their SPT and make confession about their real tax; henceforth they will be more compliant on tax in the future. Contribution of this study is to give positive discourse that can be used by the central government as feedback on tax amnesty policy as embodied in RUU national amnesty.