bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbiology of secondary infections in Buruli ulcer lesions; implications for therapeutic interventions
Authors: Gyamfi Elizabeth , Narh Charles A , Quaye Charles , Abbass Adiza , Dzudzor Bartholomew , Mosi Lydia 
Published: January 2021

Abstract
Background
Buruli ulcer (BU) is a skin disease caused by Mycobacterium ulcerans and is the second most common mycobacterial disease after tuberculosis in Ghana and Côte d’Ivoire. M. ulcerans produces mycolactone, an immunosuppressant macrolide toxin, responsible for the characteristic painless nature of the infection. Secondary infection of ulcers before, during and after treatment has been associated with delayed wound healing and resistance to streptomycin and rifampicin. However, not much is known of the bacteria causing these infections as well as antimicrobial drugs for treating the secondary microorganism. This study sought to identify secondary microbial infections in BU lesions and to determine their levels of antibiotic resistance due to the prolonged antibiotic therapy required for Buruli ulcer.

Results
Swabs from fifty-one suspected BU cases were sampled in the Amansie Central District from St. Peters Hospital (Jacobu) and through an active case surveillance. Forty of the samples were M. ulcerans (BU) positive. Secondary bacteria were identified in all sampled lesions (N = 51). The predominant bacteria identified in both BU and Non-BU groups were Staphylococci spp and Bacilli spp. The most diverse secondary bacteria were detected among BU patients who were not yet on antibiotic treatment. Fungal species identified were Candida spp, Penicillium spp and Trichodema spp. Selected secondary bacteria isolates were all susceptible to clarithromycin and amikacin among both BU and Non-BU patients. Majority, however, had high resistance to streptomycin.

Conclusions
Microorganisms other than M. ulcerans colonize and proliferate on BU lesions. Secondary microorganisms of BU wounds were mainly Staphylococcus spp, Bacillus spp and Pseudomonas spp. These secondary microorganisms were less predominant in BU patients under treatment compared to those without treatment. The delay in healing that are experienced by some BU patients could be as a result of these bacteria and fungi colonizing and proliferating in BU lesions. Clarithromycin and amikacin are likely suitable drugs for clearance of secondary infection of Buruli ulcer.
Comparative efficacy and safety of adjuvant nivolumab versus other treatments in adults with resected melanoma: a systematic literature review and network meta-analysis
Authors: Toor Kabirraaj , Middleton Mark R. , Chan Keith , Amadi Adenike , Moshyk Andriy , Kotapati Srividya 
Published: January 2021

Abstract
Background
Immune checkpoint inhibitors and targeted therapies are approved for adjuvant treatment of patients with resected melanoma; however, they have not been compared in randomized controlled trials (RCTs). We compared the efficacy and safety of adjuvant nivolumab with other approved treatments using available evidence from RCTs in a Bayesian network meta-analysis (NMA).

Methods
A systematic literature review was conducted through May 2019 to identify relevant RCTs evaluating approved adjuvant treatments. Outcomes of interest included recurrence-free survival (RFS)/disease-free survival (DFS), distant metastasis-free survival (DMFS), all-cause grade 3/4 adverse events (AEs), discontinuations, and discontinuations due to AEs. Time-to-event outcomes (RFS/DFS and DMFS) were analyzed both assuming that hazard ratios (HRs) are constant over time and that they vary.

Results
Of 26 identified RCTs, 19 were included in the NMA following a feasibility assessment. Based on HRs for RFS/DFS, the risk of recurrence with nivolumab was similar to that of pembrolizumab and lower than that of ipilimumab 3 mg/kg, ipilimumab 10 mg/kg, or interferon. Risk of recurrence with nivolumab was similar to that of dabrafenib plus trametinib at 12 months, however, was lower beyond 12 months (HR [95% credible interval] at 24 months, 0.46 [0.27–0.78]; at 36 months, 0.28 [0.14–0.59]). Based on HRs for DMFS, the risk of developing distant metastases was lower with nivolumab than with ipilimumab 10 mg/kg or interferon and was similar to dabrafenib plus trametinib.

Conclusion
Adjuvant therapy with nivolumab provides an effective treatment option with a promising risk–benefit profile.
The implications of clinical risk factors, CAR index, and compositional changes of immune cells on hyperprogressive disease in non-small cell lung cancer patients receiving immunotherapy
Authors: Kim Seo Ree , Chun Sang Hoon , Kim Joo Ri , Kim Sang-Yeob , Seo Jun Young , Jung Chan Kwon , Gil Bo-Mi , Kim Jeong-Oh , Ko Yoon Ho , Woo In Sook , Shim Byoung Yong , Hong Sook-Hee , Kang Jin Hyoung 
Published: January 2021

Abstract
Background
Immune checkpoint blockades (ICBs) are characterized by a durable clinical response and better tolerability in patients with a variety of advanced solid tumors. However, we not infrequently encounter patients with hyperprogressive disease (HPD) exhibiting paradoxically accelerated tumor growth with poor clinical outcomes. This study aimed to investigate implications of clinical factors and immune cell composition on different tumor responses to immunotherapy in patients with non-small cell lung cancer (NSCLC).

Methods
This study evaluated 231 NSCLC patients receiving ICBs between January 2014 and May 2018. HPD was defined as a > 2-fold tumor growth kinetics ratio during ICB therapy and time-to-treatment failure of ≤2 months. We analyzed clinical data, imaging studies, periodic serologic indexes, and immune cell compositions in tumors and stromata using multiplex immunohistochemistry.

Results
Of 231 NSCLC patients, PR/CR and SD were observed in 50 (21.6%) and 79 (34.2%) patients, respectively and 26 (11.3%) patients met the criteria for HPD. Median overall survival in poor response groups (HPD and non-HPD PD) was extremely shorter than disease-controlled group (SD and PR/CR) (5.5 and 6.1 months vs. 16.2 and 18.3 months, respectively, P = 0.000). In multivariate analysis, HPD were significantly associated with heavy smoker (p = 0.0072), PD-L1 expression ≤1% (p = 0.0355), and number of metastatic site ≥3 (p = 0.0297). Among the serologic indexes including NLR, PLR, CAR, and LDH, only CAR had constantly significant correlations with HPD at the beginning of prior treatment and immunotherapy, and at the 1st tumor assessment. The number of CD4+ effector T cells and CD8+ cytotoxic T cells, and CD8+/PD-1+ tumor-infiltrating lymphocytes (TIL) tended to be smaller, especially in stromata of HPD group. More M2-type macrophages expressing CD14, CD68 and CD163 in the stromal area and markedly fewer CD56+ NK cells in the intratumoral area were observed in HPD group.

Conclusions
Our study suggests that not only clinical factors including heavy smoker, very low PD-L1 expression, multiple metastasis, and CAR index, but also fewer CD8+/PD-1+ TIL and more M2 macrophages in the tumor microenvironment are significantly associated with the occurrence of HPD in the patients with advanced/metastatic NSCLC receiving immunotherapy.
Advance directives and end-of-life care: knowledge and preferences of patients with brain Tumours from Anhui, China
Authors: Wang Yixin , Zhang Yongkang , Hong Yang , Zeng Ping , Hu Zongtao , Xu Xiuli , Wang Hongzhi 
Published: January 2021

Abstract
Background
In Mainland China, advance directives (ADs) and end-of-life care for patients with tumours, especially patients with brain tumours who may have lost consciousness or the ability to speak at the early stage of their illness, have been poorly acknowledged. Thus, this study aimed to clarify the knowledge and preferences of ADs and end-of-life care in patients with brain tumours and to investigate predictors of patient preferences.

Methods
This was a population-based cross-sectional survey that was conducted via face-to-face interviews. Information on sociodemographic factors, brain tumour illness, knowledge and preferences of the advanced decisions and end-of-life care of the patients was collected.

Results
A total of 88.61% of participants had never heard of ADs, but 65.18% reported that they would like to make ADs. Knowledge of ADs, receiving surgical treatment or radiotherapy, being younger than 70 years old, being male, having educational qualifications of college or beyond, being childless, having medical insurance for nonworking or working urban residents and self-paying medical expenses were predictors of preference for making ADs. A total of 79.43% of participants wanted to discuss end-of-life arrangements with medical staff, and 63.29% of participants were willing to receive end-of-life care, even though it would not delay death. A total of 65.82% of patients with brain tumours wanted resuscitation, and as many as 45.45% of the patients thought that they did not need life support if they were in a persistent vegetative state. Brain primary tumours, being younger than 70 years old, male sex, educational qualification of junior middle school or below, having children, having new rural cooperative medical insurance and having medical expenses paid by children or spouses were predictors of choosing appropriate palliative care.

Conclusions
ADs and end-of-life care have been poorly acknowledged among patients with brain tumours in mainland China. Additional efforts should be encouraged amongst patients with primary brain tumours, those who are undergoing surgery and radiotherapy and those who have low socioeconomic status. A longitudinal and comprehensive study is encouraged to promote disease-specific ADs among Chinese patients with brain tumours.
Comparison of antimicrobial prescription patterns in calves in Switzerland before and after the launch of online guidelines for prudent antimicrobial use
Authors: Hubbuch Alina , Peter Ruth , Willi Barbara , Hartnack Sonja , Müntener Cedric , Naegeli Hanspeter , Gerspach Christian 
Published: January 2021

Abstract
Background
The increasing threat of bacterial resistance promotes the need for antibiotic stewardship programs to foster responsible antimicrobial use. Therefore, guidelines for prudent use supported by an online stewardship tool (AntibioticScout.ch) were introduced in Switzerland in December 2016. They recommend (with decreasing preference) a first, second or third line antimicrobial for treatment. The objective of this study was to evaluate antimicrobial prescriptions for Swiss calves before (2016) and after (2018) the launch of these guidelines. Cases of calves with pneumonia, diarrhea and otitis from a university hospital and eight private practices in Switzerland were included. Data on anamnesis, clinical findings, diagnostic work-up and treatment were collected. Type and percentages [95% confidence interval] of antimicrobial prescriptions were compared between 2016 and 2018.

Results
Of the total number of calves, 88.2% [85.4–90.6] in 2016 (n = 625) and 88.4% [85.7–90.7] in 2018 (n = 655) were treated with antibiotics. The use of highest priority critically important antimicrobials (HPCIAs) decreased from 52.7% [48.6–56.9] in 2016 to 38.0% [34.2–41.9] in 2018; this decrease was found at the university hospital and in private practice and in cases with pneumonia and diarrhea. Particularly the use of fluoroquinolones decreased (2016: 43.1% [39.2–47.2]; 2018: 31.1% [27.6–34.8]). Overall, the number of first line treatments increased from 12.8% [10.4–15.6] in 2016 to 20.2% [17.3–23.4] in 2018. In cases of pneumonia, first line treatments increased (2016: 15.3% [11.6–19.9]; 2018: 26.5% [21.8–31.9]) and third line treatments decreased (2016: 43.5% [38.0–49.3]; 2018: 27.9% [23.1–33.3]); this was seen at the university hospital, whereas in private practice only a decrease of third line treatments was observed. In cases of diarrhea, more second line at the expense of unlisted antimicrobials were prescribed at the university hospital in 2018. Antimicrobial treatment of calves with otitis did not change from 2016 to 2018.

Conclusions
After the introduction of AntibioticScout.ch, more prudent use was observed in the treatment of calves with pneumonia and diarrhea as less HPCIAs, particularly fluoroquinolones, and more first line antimicrobials were prescribed. However, the overall frequency of antimicrobial treatment did not change and the use of HPCIAs was still common in 2018, especially in private practices. Therefore, further antimicrobial stewardship activities are necessary.
Association between the Mediterranean lifestyle, metabolic syndrome and mortality: a whole-country cohort in Spain
Authors: Sotos-Prieto Mercedes , Ortolá Rosario , Ruiz-Canela Miguel , Garcia-Esquinas Esther , Martínez-Gómez David , Lopez-Garcia Esther , Martínez-González Miguel Ángel , Rodriguez-Artalejo Fernando 
Published: January 2021

Abstract
Background
Evidence is limited about the joint health effects of the Mediterranean lifestyle on cardiometabolic health and mortality. The aim of this study was to evaluate the association of the Mediterranean lifestyle with the frequency of the metabolic syndrome (MS) and the risk of all-cause and cardiovascular mortality in Spain.

Methods
Data were taken from ENRICA study, a prospective cohort of 11,090 individuals aged 18+ years, representative of the population of Spain, who were free of cardiovascular disease (CVD) and diabetes at 2008–2010 and were followed-up to 2017. The Mediterranean lifestyle was assessed at baseline with the 27-item MEDLIFE index (with higher score representing better adherence).

Results
Compared to participants in the lowest quartile of MEDLIFE, those in the highest quartile had a multivariable-adjusted odds ratio 0.73 (95% confidence interval (CI) 0.5, 0.93) for MS, 0.63. (0.51, 0.80) for abdominal obesity, and 0.76 (0.63, 0.90) for low HDL-cholesterol. Similarly, a higher MELDIFE score was associated with lower HOMA-IR and highly-sensitivity C-reactive protein (P-trend < 0.001). During a mean follow-up of 8.7 years, 330 total deaths (74 CVD deaths) were ascertained. When comparing those in highest vs. lowest quartile of MEDLIFE, the multivariable-adjusted hazard ratio (95% CI) was 0.58 (0.37, 0.90) for total mortality and 0.33 (0.11, 1.02) for cardiovascular mortality.

Conclusions
The Mediterranean lifestyle was associated with lower frequency of MS and reduced all-cause mortality in Spain. Future studies should determine if this also applies to other Mediterranean countries, and also improve cardiovascular health outside the Mediterranean basin.
Socio-economic determinants of malaria in tribal dominated Mandla district enrolled in Malaria Elimination Demonstration Project in Madhya Pradesh
Authors: Sharma Ravendra K. , Rajvanshi Harsh , Bharti Praveen K. , Nisar Sekh , Jayswar Himanshu , Mishra Ashok K. , Saha Kalyan B. , Shukla Man Mohan , Das Aparup , Kaur Harpreet , Wattal Suman L. , Lal Altaf A. 
Published: January 2021

Abstract
Background
Malaria is known as a disease of poverty because of its dominance in poverty-stricken areas. Madhya Pradesh state in central India is one of the most vulnerable states for malaria morbidity and mortality. Socio-economic, environmental and demographic factors present challenges in malaria control and elimination. As part of the Malaria Elimination Demonstration Project in the tribal district of Mandla in Madhya Pradesh, this study was undertaken to assess the role of different social-economic factors contributing to malaria incidence.

Methods
The study was conducted in the 1233 villages of district Mandla, where 87% population resides in rural areas. The data was collected using the android based mobile application—SOCH for a period of 2 years (September 2017 to August 2019). A wealth index was computed along with analysis of the socio-economic characteristics of houses with malaria cases. Variables with significant variation in malaria cases were used in logistic regression.

Results
More than 70% of houses in Mandla are Kuccha (made of thatched roof or mud), 20% do not have any toilet facilities, and only 11% had an annual income of more than 50,000 INR, which converts to about $700 per year. Households with younger heads, male heads, more number of family members were more likely to have malaria cases. Kuccha construction, improper water supply, low household income houses were also more likely to have a malaria case and the odds doubled in houses with no toilet facilities.

Conclusion
Based on the results of the study, it has been found that there is an association between the odds of having malaria cases and different household variables such as age, gender, number of members, number of rooms, caste, type of house, toilet facilities, water supply, cattle sheds, agricultural land, income, and vector control interventions. Therefore, a better understanding of the association of various risk factors that influence the incidence of malaria is required to design and/or deploy effective policies and strategies for malaria elimination. The results of this study suggest that appropriate economic and environmental interventions even in low-income and poverty-stricken tribal areas could have huge impact on the success of the national malaria elimination goals.
Mer regulates microglial/macrophage M1/M2 polarization and alleviates neuroinflammation following traumatic brain injury
Authors: Wu Haijian , Zheng Jingwei , Xu Shenbin , Fang Yuanjian , Wu Yingxi , Zeng Jianxiong , Shao Anwen , Shi Ligen , Lu Jianan , Mei Shuhao , Wang Xiaoyu , Guo Xinying , Wang Yirong , Zhao Zhen , Zhang Jianmin 
Published: January 2021

Abstract
Background
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Microglial/macrophage activation and neuroinflammation are key cellular events following TBI, but the regulatory and functional mechanisms are still not well understood. Myeloid-epithelial-reproductive tyrosine kinase (Mer), a member of the Tyro-Axl-Mer (TAM) family of receptor tyrosine kinases, regulates multiple features of microglial/macrophage physiology. However, its function in regulating the innate immune response and microglial/macrophage M1/M2 polarization in TBI has not been addressed. The present study aimed to evaluate the role of Mer in regulating microglial/macrophage M1/M2 polarization and neuroinflammation following TBI.

Methods
The controlled cortical impact (CCI) mouse model was employed. Mer siRNA was intracerebroventricularly administered, and recombinant protein S (PS) was intravenously applied for intervention. The neurobehavioral assessments, RT-PCR, Western blot, magnetic-activated cell sorting, immunohistochemistry and confocal microscopy analysis, Nissl and Fluoro-Jade B staining, brain water content measurement, and contusion volume assessment were performed.

Results
Mer is upregulated and regulates microglial/macrophage M1/M2 polarization and neuroinflammation in the acute stage of TBI. Mechanistically, Mer activates the signal transducer and activator of transcription 1 (STAT1)/suppressor of cytokine signaling 1/3 (SOCS1/3) pathway. Inhibition of Mer markedly decreases microglial/macrophage M2-like polarization while increases M1-like polarization, which exacerbates the secondary brain damage and sensorimotor deficits after TBI. Recombinant PS exerts beneficial effects in TBI mice through Mer activation.

Conclusions
Mer is an important regulator of microglial/macrophage M1/M2 polarization and neuroinflammation, and may be considered as a potential target for therapeutic intervention in TBI.
Association of calprotectin with other inflammatory parameters in the prediction of mortality for ischemic stroke
Authors: Marta-Enguita Juan , Navarro-Oviedo Manuel , Rubio-Baines Idoia , Aymerich Nuria , Herrera Maria , Zandio Beatriz , Mayor Sergio , Rodriguez Jose-Antonio , Páramo Jose-Antonio , Toledo Estefania , Mendioroz Maite , Muñoz Roberto , Orbe Josune 
Published: January 2021

Abstract
Background
Inflammatory response plays an important role in many processes related to acute ischemic stroke (AIS). Calprotectin (S100A8/S100A9), released by monocytes and neutrophils, is a key protein in the regulation of inflammation and thrombosis. The purpose of this study is to evaluate the association of circulating calprotectin with other inflammatory biomarkers and AIS prognosis, as well as the calprotectin content in stroke thrombi.

Methods
Among the 748 patients treated at a comprehensive stroke center between 2015 and 2017, 413 patients with confirmed acute ischemic injury were prospectively evaluated. Patients with systemic inflammation or infection at onset were excluded. Plasma calprotectin was measured by ELISA in blood samples of AIS patients within the first 24 h. Univariate and multivariate logistic regression models were performed to evaluate its association with mortality and functional independence (FI) at 3 months (defined as modified Rankin Scale < 3) and hemorrhagic transformation (HT) after ischemic stroke. Further, S100A9 was localized by immunostaining in stroke thrombi (n = 44).

Results
Higher calprotectin levels were associated with 3-month mortality, HT, and lower 3-month FI. After adjusting for potential confounders, plasma calprotectin remained associated with 3-month mortality [OR (95% CI) 2.31 (1.13–4.73)]. Patients with calprotectin ≥ 2.26 μg/mL were 4 times more likely to die [OR 4.34 (1.95–9.67)]. Addition of calprotectin to clinical variables led to significant improvement in the discrimination capacity of the model [0.91 (0.87–0.95) vs 0.89 (0.85–0.93); p < 0.05]. A multimarker approach demonstrated that patients with increased calprotectin, CRP, and NLR had the poorest outcome with a mortality rate of 42.3% during follow-up. S100A9 protein, as part of the heterodimer calprotectin, was present in all thrombi retrieved from AIS patients. Mean S100A9 content was 3.5% and tended to be higher in patients who died (p = 0.09). Moreover, it positively correlated with platelets (Pearson r 0.46, p < 0.002), leukocytes (0.45, p < 0.01), and neutrophil elastase (0.70, p < 0.001) thrombus content.

Conclusions
Plasma calprotectin is an independent predictor of 3-month mortality and provides complementary prognostic information to identify patients with poor outcome after AIS. The presence of S100A9 in stroke thrombi suggests a possible inflammatory mechanism in clot formation, and further studies are needed to determine its influence in resistance to reperfusion.