bluuebunny/crossref_metadata_2025_split huggingface dataset:
Consumption Trends of Antibiotic for Veterinary Use in Tanzania: A Longitudinal Retrospective Survey From 2010-2017
Authors: Sangeda Raphael Z. , Baha Andrea , Erick Alexander , Mkumbwa Sonia , Bitegeko Adonis , Sillo Hiiti B. , Fimbo Adam M. , Chambuso Mhina , Mbugi Erasto V. 
Published: June 2021

BackgroundWith increased livestock keeping, multiple prevailing infections, antimicrobial agents’ use and pattern in Tanzania, the development of antimicrobial resistance (AMR) becomes inevitable. Antibiotic-resistant pathogens have increasingly become a major challenge in human and animal medicine. Although inappropriate use of antibiotics in humans is the principal cause of resistance, antibiotic-resistant bacteria originating from animals contribute to the emergence and spread of these bacteria. Antibiotics help control a multitude of bacterial infections that are major causes of diseases in both animals and humans. Rational use in animals is crucial to control any development and transfer of AMR to humans. This study aimed to create quantitative evidence of animal antimicrobial usage patterns in Tanzania to serve as a baseline for surveillance of antimicrobial use and antimicrobial resistance control.MethodologyThis descriptive longitudinal retrospective study was conducted to explore the trend of veterinary-antibiotics consumed in the eight years, from 1st January 2010 to 31st December 2017 in Tanzania mainland. The data source was records of all antibiotics imported for veterinary use into Tanzania’s mainland according to the Tanzania Medicines and Medical Devices Authority (TMDA) records. The analysis employed the World Health Organization (WHO) Collaborating Centre for Drug Statistics Methodology using Anatomical Therapeutic and Chemical (ATC) classification. Regression and time series analysis was used to establish trends in antibiotics consumption.ResultsA total of 12,147,491 kg of antibiotics were consumed in Tanzania from 2010 to 2017. Tetracycline, sulfonamides and trimethoprim, quinolones, aminoglycosides, beta-lactams and antibacterial combinations were the most commonly used antibacterial agents in Tanzania. Tetracycline class topped the list with about 8,090,798 kg (66.6%) out of 12,147,491 kg total quantity of antimicrobials consumed. Non-significant, linear curve estimations and time series analysis indicate a decline in the quantities of veterinary antibiotics used in the eight years from 2010 to 2017.ConclusionsThis study suggests that tetracycline is the most used antibiotic class for veterinary medicine in Tanzania. The trend of antimicrobial use is generally decreasing compared to other countries in Africa. Even though some antibiotics have the lowest consumption rate, they are also prone to AMR, prompting follow-up by the relevant regulatory authorities.
Comorbidities of Patients With Idiopathic Pulmonary Fibrosis in Four Latin American Countries. Are There Differences by Country and Altitude?
Authors: Gonzalez-Garcia Mauricio , Rincon-Alvarez Emily , Alberti Maria Laura , Duran Mauricio , Caro Fabian , Venero Maria del Carmen , Liberato Yuri Edison , Buendia-Roldan Ivette 
Published: June 2021

Background:Comorbidities in idiopathic pulmonary fibrosis (IPF) affect quality of life, symptoms, disease progression and survival. It is unknown what are the comorbidities in patients with IPF in Latin America (LA) and if there are differences between countries. Our objective was to compare IPF comorbidities in four countries and analyze possible differences by altitude.Methods:Patients with IPF according 2012 ATS/ERS/JRS/ALAT guidelines, from two cities with an altitude of ≥2,250 m: Mexico City (Mexico) and Bogotá (Colombia) and from three at sea level: Buenos Aires (Argentina) and Lima and Trujillo (Peru). Comorbidities and pulmonary function tests were taken from clinical records. Possible pulmonary hypertension (PH) was defined by findings in the transthoracic echocardiogram of systolic pulmonary arterial pressure (sPAP) &gt;36 mmHg or indirect signs of PH in the absence of other causes of PH. Emphysema as the concomitant finding of IPF criteria on chest tomography plus emphysema in the upper lobes. ANOVA or Kruskal Wallis and χ2-tests were used for comparison.Results:Two hundred and seventy-six patients were included, 50 from Argentina, 86 from Colombia, 91 from Mexico and 49 from Peru. There prevalence of PH was higher in Colombia and Mexico (p&lt; 0.001), systemic arterial hypertension in Argentina (p&lt; 0.015), gastro-esophageal reflux and dyslipidemia in Colombia and Argentina (p&lt; 0.001) and diabetes mellitus in Mexico (p&lt; 0.007). Other comorbidities were obesity (28.4%), coronary artery disease (15.2%) and emphysema (14.9%), with no differences between countries. There was more PH in the altitude cities than those at sea level (51.7 vs. 15.3%,p&lt; 0.001). In patients from Bogotá and Mexico City, arterial oxygen pressure, saturation (p&lt; 0.001) and carbon monoxide diffusing capacity (p= 0.004) were significantly lower than in cities at sea level.Conclusions:In this study with a significant number of patients, we were able to describe and compare the comorbidities of IPF in four LA countries, which contributes to the epidemiological data of this disease in the region. The main results were the differences in comorbidities between the countries and more PH in the subjects residing in the cities of higher altitude, a finding that should be validated in future studies.
Long-Term Increase in Cholesterol Is Associated With Better Cognitive Function: Evidence From a Longitudinal Study
Authors: Liu Huamin , Zou Lianwu , Zhou Rui , Zhang Minyi , Gu Shanyuan , Zheng Jiazhen , Hukportie Daniel Nyarko , Wu Keyi , Huang Zhiwei , Yuan Zelin , Wu Xianbo 
Published: June 2021

Background: Higher visit-to-visit cholesterol has been associated with cognitive decline. However, the association between long-term increase or decrease in cholesterol and cognitive decline remains unclear.Methods: A total of 4,915 participants aged ≥45 years with normal cognition in baseline were included. The participants were divided into four groups, namely low–low, low–high, high–low, and high–high, according to the diagnostic thresholds of total cholesterol (TC), non-high-density lipoprotein cholesterol (NHDL-C), low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) after 4 years of follow-up. Cognitive function was assessed by episodic memory and mental intactness. Binary logistic regression was used to analyse the association of cholesterol variation with cognitive decline.Results: Among the participants, 979 (19.9%) experienced global cognitive decline. The odds ratio (OR) of global cognitive and memory function decline were remarkably lower in participants in the low–high NHDL-C group than those in the low–low group [OR and 95% confidence interval (CI): 0.50 [0.26–0.95] for global cognitive decline, 0.45 [0.25–0.82] for memory function decline]. The lower OR was also significant in females (OR [95% CI]: 0.38 [0.17–0.87] for global cognitive decline; 0.44 [0.19–0.97] for memory function decline) and participants without cardiovascular disease (OR [95% CI]: 0.31 [0.11–0.87] for global cognitive decline; 0.34 [0.14–0.83] for memory function decline). The increases in other cholesterol were also negatively associated with the risk of cognitive decline although not significantly.Conclusions: A longitudinal increase in NHDL-C may be protective for cognition in females or individuals without cardiovascular disease.
Differences Changes in Cerebellar Functional Connectivity Between Mild Cognitive Impairment and Alzheimer's Disease: A Seed-Based Approach
Authors: Tang Fanyu , Zhu Donglin , Ma Wenying , Yao Qun , Li Qian , Shi Jingping 
Published: June 2021

Background: Recent studies have discovered that functional connections are impaired among patients with Alzheimer's disease (AD), even at the preclinical stage. The cerebellum has been implicated as playing a role in cognitive processes. However, functional connectivity (FC) among cognitive sub-regions of the cerebellum in patients with AD and mild cognitive impairment (MCI) remains to be further elucidated.Objective: Our study aims to investigate the FC changes of the cerebellum among patients with AD and MCI, compared to healthy controls (HC). Additionally, we explored the role of cerebellum FC changes in the cognitive performance of all subjects.Materials: Resting-state functional magnetic resonance imaging (rs-fMRI) data from three different groups (28 AD patients, 26 MCI patients, and 30 HC) was collected. We defined cerebellar crus II and lobule IX as seed regions to assess the intragroup differences of cortico-cerebellar connectivity. Bias correlational analysis was performed to investigate the relationship between changes in FC and neuropsychological performance.Results: Compared to HC, AD patients had decreased FC within the caudate, limbic lobe, medial frontal gyrus (MFG), middle temporal gyrus, superior frontal gyrus, parietal lobe/precuneus, inferior temporal gyrus, and posterior cingulate gyrus. Interestingly, MCI patients demonstrated increased FC within inferior parietal lobe, and MFG, while they had decreased FC in the thalamus, inferior frontal gyrus, and superior frontal gyrus. Further analysis indicated that FC changes between the left crus II and the right thalamus, as well as between left lobule IX and the right parietal lobe, were both associated with cognitive decline in AD. Disrupted FC between left crus II and right thalamus, as well as between left lobule IX and right parietal lobe, was associated with attention deficit among subjects with MCI.Conclusion: These findings indicate that cortico-cerebellar FC in MCI and AD patients was significantly disrupted with different distributions, particularly in the default mode networks (DMN) and fronto-parietal networks (FPN) region. Increased activity within the fronto-parietal areas of MCI patients indicated a possible compensatory role for the cerebellum in cognitive impairment. Therefore, alterations in the cortico-cerebellar FC represent a novel approach for early diagnosis and a potential therapeutic target for early intervention.
Changes of Regional Neural Activity Homogeneity in Preclinical Alzheimer’s Disease: Compensation and Dysfunction
Authors: Zhang Zhen , Cui Liang , Huang Yanlu , Chen Yu , Li Yuehua , Guo Qihao 
Published: June 2021

IntroductionSubjective cognitive decline (SCD) is the preclinical stage of Alzheimer’s disease and may develop into amnestic mild cognitive impairment (aMCI). Finding suitable biomarkers is the key to accurately identifying SCD. Previous resting-state functional magnetic resonance imaging (rs-fMRI) studies on SCD patients showed functional connectivity disorders. Our goal was to explore whether local neurological homogeneity changes in SCD patients, the relationship between these changes and cognitive function, and similarities of neurological homogeneity changes between SCD and aMCI patients.Materials and Methods37 cases of the healthy control (HC) group, 39 cases of the SCD group, and 28 cases of the aMCI group were included. Participants underwent rs-fMRI examination and a set of neuropsychological test batteries. Regional homogeneity (ReHo) was calculated and compared between groups. ReHo values were extracted from meaningful regions in the SCD group, and the correlation between ReHo values with the performance of neuropsychological tests was analyzed.ResultsOur results showed significant changes in the ReHo among groups. In the SCD group compared with the HC group, part of the parietal lobe, frontal lobe, and occipital lobe showed decreased ReHo, and the temporal lobe, part of the parietal lobe and the frontal lobe showed increased ReHo. The increased area of ReHo was negatively correlated with the decreased area, and was related to decrease on multiple neuropsychological tests performance. Simultaneously, the changed areas of ReHo in SCD patients are similar to aMCI patients, while aMCI group’s neuropsychological test performance was significantly lower than that of the SCD group.ConclusionThere are significant changes in local neurological homogeneity in SCD patients, and related to the decline of cognitive function. The increase of neurological homogeneity in the temporal lobe and adjacent area is negatively correlated with cognitive function, reflecting compensation for local neural damage. These changes in local neurological homogeneity in SCD patients are similar to aMCI patients, suggesting similar neuropathy in these two stages. However, the aMCI group’s cognitive function was significantly worse than that of the SCD group, suggesting that this compensation is limited. In summary, regional neural activity homogeneity may be a potential biomarker for identifying SCD and measuring the disease severity.
Serum Tumor Markers Combined With Clinicopathological Characteristics for Predicting MMR and KRAS Status in 2279 Chinese Colorectal Cancer Patients: A Retrospective Analysis
Authors: Zhao Ning , Cao Yinghao , Yang Jia , Li Hang , Wu Ke , Wang Jiliang , Peng Tao , Cai Kailin 
Published: June 2021

Although serum tumor markers (STMs), clinicopathological characteristics and the status of KRAS and MMR play an important role in optimizing the treatment and prognosis of colorectal cancer, their interrelationships remain largely unknown. A retrospective analysis of 2279 patients who tested for KRAS and MMR status, and STM measurements prior to treatment over the past four years was conducted. Of the 784 patients tested for KRAS and 2279 patients tested for MMR status, KRAS mutations and dMMR were identified in 276 patients (35.20%) and 177 patients (7.77%), respectively. Logistic regression analysis demonstrated that right colon, well and moderate differentiation and negative CA19-9 were independent predictors for KRAS mutations. The ROC curve yielded an AUC of 0.609 through the combination of these three factors. Age &lt; 65 was an independent predictive factor for dMMR, along with tumor size &gt; 4.6 cm, right colon, poor differentiation, harvested lymph nodes ≥ 22, no lymph node metastasis, no perineural invasion, negative CEA and positive CA72-4. When the nine criteria were used together, the AUC was 0.849. In summary, both STMs and clinicopathological characteristics were found to be significantly associated with the status of KRAS and MMR. The combination of these two factors possessed a strong predictive power for KRAS mutations and dMMR among CRC patients.
Does kV Image Guidance for Bone Metastases Improve Pain Control?
Authors: Tunceroglu Ahmet S. , Gui Bin , Lu Shou-En , Sison Julian , Parikh Rahul , Goyal Sharad , Haffty Bruce G. , Kim Sung , Jabbour Salma K. 
Published: June 2021

Purpose/ObjectivesDespite its widespread availability, the use of kilovoltage (kV) image guidance is often related to factors such as perceived adequacy of clinical patient setup and individual practice patterns. We sought to determine whether kV image guidance in the treatment of painful bone metastases would improve therapeutic efficacy.Materials/MethodsUnder an Institutional Review Board approved protocol, hospital records of 164 patients having received radiation therapy to 257 individual painful osseous metastases were retrospectively reviewed. Marginal logistic regression analyses using the generalized estimating equation (GEE) approach were used to investigate potential associations between pain reduction and several patient, disease, and treatment related variables. Correlation of kV image guidance with pain reduction was analyzed by univariate and multivariate GEE logistic regression analysis.ResultsMedian time to pain reduction was 3 days (range 0~109 days) from the start of radiation therapy. Pain reduction ≥ 50% was noted in 196 (77%) metastatic lesions with 136 (53%) demonstrating complete pain relief. Patients with metastatic lesions from non-small cell lung cancer experienced less pain relief (p = 0.007). Disease extension outside of bone was a negative predictor for pain reduction (p = 0.02). On univariate and multivariate logistic regression, kV image guidance demonstrated a statistically significant correlation with improved pain control in cases involving treatment of the lower extremities (p = 0.03) and those with fewer treatment fractions (p = 0.01), particularly in the setting of extra-osseous disease extension (p = 0.003).ConclusionsKilovoltage image guidance in the treatment of painful bone metastases may offer greater pain control through improved patient setup, particularly for patients with tumors of the lower extremities, extraosseous disease extension, and fewer treatment fractions.
PD-1 Inhibitors Could Improve the Efficacy of Chemotherapy as First-Line Treatment in Biliary Tract Cancers: A Propensity Score Matching Based Analysis
Authors: Gou Miaomiao , Zhang Yong , Liu Tiee , Si Haiyan , Wang Zhikuan , Yan Huan , Qian Niansong , Dai Guanghai 
Published: June 2021

BackgroundThere are limited treatment options for advanced biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma, extrahepatic bile duct cancer, gallbladder cancer. We compared the efficacy and safety of PD-1 inhibitors plus chemotherapy and chemotherapy alone as first-line treatment in patients with advanced BTC.MethodsWe retrospectively reviewed patients with BTC treated at the oncology department of the Chinese PLA general hospital receiving PD-1 inhibitor with chemotherapy (anti-PD-1+C group) or chemotherapy alone (C group). Propensity Score Matching (PSM) (1:1) was performed to balance potential baseline confounding factors. Progression-free survival (PFS) was analyzed using Kaplan–Meier survival curves with log-rank tests. Objective response rate (ORR), disease control rate (DCR), and safety were also analyzed.ResultsThis study included 75 patients who received PD-1 inhibitors (including Pembrolizumab, Nivolumab, Sintilimab, Toripalimab) plus chemotherapy and 59 patients who received chemotherapy alone. After matching, there were no significant differences between the two groups for baseline characteristics. Within the matched cohort, the median PFS was 5.8m in the anti-PD-1+C group, which was significantly longer than the C group, at 3.2m (HR: 0.47, 95% CI 0.29 to 0.76, P = 0.004). The ORR was 21.7% and DCR was 80.4% in the anti-PD-1+C group, while the ORR was 15.2% and DCR was 69.6% in the C group. No significant differences were found in the ORR and DCR between the two groups (P=0.423, P=0.231). Grade 3 or 4 treatment was related to adverse events (AEs) that occurred in the anti-PD-1+C group, namely hypothyroidism (n=3, 6.5%), rash (n=2, 4.2%), and hepatitis (n=1, 2.2%). There was no AE-related death. The grade 3-4 leukopenia rate was similar in the two groups (4.3% vs. 6.5%).ConclusionsAnti-PD-1 therapy plus chemotherapy prolonged the PFS compared with chemotherapy alone in advanced BTC with controllable AEs. Further clinical trials are needed to confirm this result.
De Novo Mutation in Non-Tyrosine Kinase Domain of ROS1 as a Potential Predictor of Immune Checkpoint Inhibitors in Melanoma
Authors: Ma Si-Cong , Zhu Hong-Bo , Wang Jian , Zhang Yan-Pei , Guo Xue-Jun , Long Li-Li , Guo Ze-Qin , Wu De-Hua , Dong Zhong-Yi , Bai Xue 
Published: June 2021

PurposeDespite the success of targeted therapy in c-ros oncogene 1 (ROS1)-rearranged cancers, especially non-small cell lung cancer (NSCLC), the clinical significance of ROS1 de novo mutation has not yet been understood. We sought to elucidate the predictive effect of ROS1 mutation for immune checkpoint inhibitor (ICI) therapy in melanoma.MethodsThe Cancer Genome Atlas [TCGA (n = 10967)] and Memorial Sloan Kettering Cancer Center [MSK (n = 10,945)] datasets, as well as two clinical cohorts of melanoma received ICI [CA209-038 (n = 73) and MEL-IPI (n = 110)], were included to explore the prevalence, prognostic effect, and immunotherapeutic predictive effect of ROS1 mutation in melanoma. Overall survival (OS) was defined as the primary outcome.ResultsOverall, melanoma accounted for the highest proportion of ROS1 mutation (~20%) which made up the majority (~95%) of the ROS1-alterated cases. Remarkably, ROS1 mutation yielded longer OS from ICI than the wild-type counterpart in the MSK melanoma population [hazard ratio (HR) 0.47, 95% confidence interval (CI) 0.30–0.74], and two external melanoma cohorts (CA209-038: HR 0.42, 95% CI 0.20–0.89; MEL-IPI: HR 0.55, 95% CI 0.34–0.91), without affecting the prognosis of patients. Elevated tumor mutational burden and enrichment of DNA damage repair was observed in ROS1 mutated patients, providing an explanation for the favorable responses to ICI therapy. Precisely, ROS1 mutation in non-protein tyrosine kinase (PTK) domain but not PTK mutation was responsible for the immunotherapy-specific responses of the ROS1 mutated patients in melanoma.ConclusionsCollectively, ROS1 mutation, specifically the non-PTK mutation, is a potential predictor of ICI therapy in melanoma, which is distinct from the well-established role of ROS1 rearrangement for targeted therapy in NSCLC.
Development and Validation of a Nomogram for the Prediction of Inguinal Lymph Node Metastasis Extranodal Extension in Penile Cancer
Authors: Wu Chong , Li Zaishang , Guo Shengjie , Zhou Fangjian , Han Hui 
Published: June 2021

PurposeTo determine whether a clinicopathologic and laboratory-based nomogram is capable of predicting the risk of lymph node extranodal extension (ENE) in patients with penile cancer.Materials and MethodsFrom June 2006 to January 2021, 234 patients who underwent bilateral inguinal lymph node dissection (ILND) surgery were included in the analysis. A Lasso regression model was utilized to select the most useful predictive features from among 46 laboratory variables. Then, a logistic regression analysis was used to develop the prediction model. Calibration curves, concordance index (C-index) and Areas under the receiver-operating characteristic curves (AUCs) were performed to evaluate the performance of the nomogram. We also investigated model fit using changes in Akaike Information Criteria (AICs). Decision curve analyses (DCAs) were applied to assess the clinical usefulness of this nomograms. Its internal validation was confirmed.ResultsAmong the 234 patients, 53 were confirmed to have ENE. The platelet-lymphocyte ratio (PLR) and Squamous cell carcinoma antigen (SCC-Ag) were significantly associated with ENE (P&lt;0.05). The individualized prediction nomogram, including the PLR, SCC-Ag, lymphovascular invasion (LVI), and pathologic tumor stage(pT-stage), showed good discrimination, with a C-index of 0.817 (95% CI, 0.745 to 0.890) and good calibration. Clinical-laboratory nomogram (AIC, 180.034) become the best-fitting model. DCA findings revealed that the clinical-laboratory nomogram was more clinically useful than the pT-stage or tumor grade.ConclusionsThis study presents a clinicopathologic and laboratory-based nomogram that incorporates PLR, SCC-Ag, lymphovascular invasion (LVI), and pT-stage, which can be conveniently utilized to facilitate the individualized prediction of lymph node metastasis ENE in patients with penile cancer.