bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stakeholder views on the acceptability of Human Infection Studies in Malawi
Authors: Kapumba Blessings M. , Jambo Kondwani , Rylance Jamie , Gmeiner Markus , Sambakunsi Rodrick , Parker Michael , Gordon Stephen B. , Gooding Kate 
Published: January 2020

Abstract
Background: Human infection studies (HIS) are valuable in vaccine development. Deliberate infection, however, creates challenging questions, particularly in low and middle-income countries (LMICs) where HIS are new and ethical challenges may be heightened. Consultation with stakeholders is needed to support contextually appropriate and acceptable study design. We examined stakeholder perceptions about the acceptability and ethics of HIS in Malawi, to inform decisions about planned pneumococcal challenge research and wider understanding of HIS ethics in LMICs. Methods: We conducted 6 deliberative focus groups and 15 follow-up interviews with research staff, medical students, and community representatives from rural and urban Blantyre. We also conducted 5 key informant interviews with clinicians, ethics committee members, and district health government officials. Results: Stakeholders perceived HIS research to have potential population health benefits, but they also had concerns, particularly related to the safety of volunteers and negative community reactions. Acceptability depended on a range of conditions related to procedures for voluntary and informed consent, inclusion criteria, medical care or support, compensation, regulation, and robust community engagement. These conditions largely mirror those in existing guidelines for HIS and biomedical research in LMICs. Stakeholder perceptions pointed to potential tensions, for example, balancing equity, safety, and relevance in inclusion criteria. Conclusions: Our findings suggest HIS research could be acceptable in Malawi, provided certain conditions are in place. Ongoing assessment of participant experiences and stakeholder perceptions will be required to strengthen HIS research during development and roll-out.
Social acceptance of alcohol use in Uganda.
Authors: Ssebunnya Joshua , Kituyi Caroline , Nabanoba Justine , Nakku Juliet , Bhana Arvin , Kigozi Fred 
Published: January 2020

Abstract
Background: Alcohol use is part of many cultural, religious and social practices, and provides perceived pleasure to many users. In many societies, alcoholic beverages are a routine part of the social landscape for many in the population. Relatively low rates were reported for Alcohol Use Disorders (AUD) in a community-based survey and facility detection survey conducted in the study site contrary to findings in earlier formative studies where alcohol use was reported to be a major health problem. The aim of this study was to understand the reasons for under-reporting and the low detection rate for AUDs, exploring societal perceptions of alcohol use in the study district.Methods: The study was conducted in Kamuli District (implementation site for the PRIME project). Semi-structured interviews and focus group discussions were conducted with purposively selected participants that included local and religious leaders, lay people, health workers as well as heavy alcohol drinkers and their spouses. Interviews were tape-recorded and transcribed verbatim. The analysis followed four thematic areas, which include the extent and acceptability of alcohol use, patterns of alcohol use, perceived health problems associated with alcohol use and help-seeking behavior for persons with alcohol related problems.Results: The findings indicate that alcohol consumption in the study site was common and widely acceptable across all categories of people and only frowned upon if the person becomes a nuisance to others. These findings suggest that the health problems associated with alcohol use are overlooked except when they are life-threatening. Help-seeking for such problems was therefore reported to be relatively rare.Conclusion: Alcohol was readily available in the community and its consumption widely acceptable, with less social sanctions despite the legal restrictions to the minors. The social acceptance results in low recognition of alcohol use related health problems, consequently resulting in poor help-seeking behavior.
Adapting a nurse-led primary care initiative to cardiovascular disease control in Ghana: A qualitative study
Authors: Haykin Leah A. , Francke Jordan A. , Abapali Aurelia , Yakubu Elliasu , Dambayi Edith , Jackson Elizabeth , Aborigo Raymond , Awuni Denis , Nonterah Engelbert A. , Oduro Abraham R. , Bawah Ayaga A , Phillips James F. , Heller David J 
Published: January 2020

Abstract

Background: Cardiovascular Disease (CVD) is a growing cause of morbidity and mortality in Ghana, where rural primary health care is provided mainly by the Community-based Health Planning and Services (CHPS) initiative. CHPS locates nurses in community-level clinics for basic curative and preventive health services and provides home and outreach services. But CHPS currently lacks capacity to screen for or treat CVD and its risk factors. Methods: In two rural districts, we conducted in-depth interviews with 21 nurses and 10 nurse supervisors to identify factors constraining or facilitating CVD screening and treatment. Audio recordings were transcribed, coded for content, and analyzed for key themes. Results: Respondents emphasized three themes: community demand for CVD care; community access to CVD care; and provider capacity to render CVD care. Nurses and supervisors noted that community members were often unaware of CVD, despite high reported prevalence of risk factors. Community members were unable to travel for care or afford treatment once diagnosed. Nurses lacked relevant training and medications for treating conditions such as hypertension. Respondents recognized the importance of CVD care, expressed interest in acquiring further training, and emphasized the need to improve ancillary support for primary care operations. Conclusions: CHPS staff expressed multiple constraints to CVD care, but also cited actions to address them: CVD-focused training, provision of essential equipment and pharmaceuticals, community education campaigns, and referral and outreach transportation equipment. Results attest to the need for trial of these interventions to assess their impact on CVD risk factors such as hypertension, depression, and alcohol abuse.
An immune-centric exploration of BRCA1 and BRCA2 germline mutation related breast and ovarian cancers
Authors: Przybytkowski Ewa , Davis Thomas , Hosny Abdelrahman , Eismann Julia , Matulonis Ursula A. , Wulf Gerburg M. , Nabavi Sheida 
Published: January 2020

Abstract
Background: BRCA1/2 germline mutation related cancers are candidates for new immune therapeutic interventions. This study was a hypothesis generating exploration of genomic data collected at diagnosis for 19 patients. The prominent tumor mutation burden (TMB) in hereditary breast and ovarian cancers in this cohort was not correlated with high global immune activity in their microenvironments. More information is needed about the relationship between genomic instability, phenotypes and immune microenvironments of these hereditary tumors in order to find appropriate markers of immune activity and the most effective anticancer immune strategies.
Methods: Mining and statistical analyses of the original DNA and RNA sequencing data and The Cancer Genome Atlas data were performed. To interpret the data, we have used published literature and web available resources such as Gene Ontology, The Cancer immunome Atlas and the Cancer Research Institute iAtlas.
Results: We found that BRCA1/2 germline related breast and ovarian cancers do not represent a unique phenotypic identity, but theyexpress a range of phenotypes similar to sporadic cancers. All breast and ovarian BRCA1/2 related tumors are characterized by high homologous recombination deficiency (HRD) and low aneuploidy. Interestingly, all sporadic high grade serous ovarian cancers (HGSOC) and most of the subtypes of triple negative breast cancers (TNBC) also express a high degree of HRD.
Conclusions: TMB is not associated with the magnitude of the immune response in hereditary BRCA1/2 related breast and ovarian cancers or in sporadic TNBC and sporadic HGSOC. Hereditary tumors express phenotypes as heterogenous as sporadic tumors with various degree of “BRCAness” and various characteristics of the immune microenvironments. The subtyping criteria developed for sporadic tumors can be applied for the classification of hereditary tumors and possibly also characterization of their immune microenvironment. A high HRD score may be a good candidate biomarker for response to platinum, and potentially PARP-inhibition.
Trial registration: Phase I Study of the Oral PI3kinase Inhibitor BKM120 or BYL719 and the Oral PARP Inhibitor Olaparib in Patients With Recurrent TNBC or HGSOC (NCT01623349), first posted on June 20, 2012. The design and the outcome of the clinical trial is not in the scope of this study.
Oral rinses in growth inhibition and treatment of Helicobacter pylori infection
Authors: Kashyap Dharmendra , Baral Budhadev , Verma Tarun Prakash , Sonkar Charu , Chatterji Debi , Jain Ajay Kumar , Jha Hem Chandra 
Published: January 2020

AbstractBackground Helicobacter pylori ( H. pylori ) is well-known for its role in chronic gastritis and gastric cancer. Eradication of these carcinogenic bacteria from the gut is one of the challenges for clinicians. The complexity of treatment mainly owes to antibiotic resistance and relapse due to an additional reservoir in the oral cavity. Our study emphases the isolation of H. pylori from distinct habitats of the gut microenvironment (gastric biopsy and gastric juice) and its subsequent characterization. We have also evaluated the effect of various oral rinses on isolated H. pylori from different anatomical locations of included subjects. Results The possible strains isolated from two different habitats of the same subject shows a striking difference in their growth pattern. Promisingly, some of the included oral rinses are efficient in growth inhibition as per recommended 30 sec treatment. The subsequent evaluation shows that oral rinse B (among A-E) is most effective and down-regulates the expression of one of the potent H. pylori gene, CagA, in the infected gastric adenocarcinoma (AGS) cells. Conclusion Our study, for the first time, revealed that H. pylori, isolated from the different habitat of the same subject, show a different growth pattern. The expression of H. pylori pathogenic gene (CagA) was down-regulated by the use of oral rinses. Hence, oral rinses will reduce the H. pylori in the oral cavity and help to control its migration from oral to the gastric compartment and may be used as an adjuvant treatment option for its re-infection.
Dynamics of plasma biomarkers in Down syndrome: the relative levels of Aβ42 decrease with age, whereas NT1 tau and NfL increase
Authors: Mengel David , Liu Wen , Glynn Robert J. , Selkoe Dennis J. , Strydom Andre , Lai Florence , Rosas H. Diana , Torres Amy , Patsiogiannis Vasiliki , Skotko Brian , Walsh Dominic 
Published: January 2020

Abstract
Background Down syndrome (DS) is the most common genetic cause of Alzheimer’s Disease (AD), but diagnosis of AD in DS is challenging due to the intellectual disability which accompanies DS. When disease-modifying agents for AD are approved, reliable biomarkers will be required to identify when and how long people with DS should undergo treatment. Three cardinal neuropathological features characterize AD, and AD in DS – Aβ amyloid plaques, tau neurofibrillary tangles, and neuronal loss. Here, we quantified plasma biomarkers of all 3 neuropathological features in a large cohort of people with DS aged from 3 months to 68 years. Methods Using ultra-sensitive single molecule array (Simoa) assays, we measured 3 analytes (Aβ42, NfL, and tau) in plasmas of 100 individuals with DS and 100 age- and sex-matched controls. Tau was measured using an assay (NT1) which detects forms of tau containing at least residues 6-198, and the stability of the 3 analytes was established using plasma from ten healthy volunteers collected at 6 intervals over a five day period. Results High Aβ42 and NT1 tau, and low NfL, were observed in infants. Across all ages, Aβ42 levels were higher in DS than controls. Levels of Aβ42 decreased with age in both DS and controls, but this decrease was greater in DS than controls and became prominent in the third decade of life. NT1 tau fell in adolescents and young adults, but increased in older individuals with DS. NfL levels were low in infants, children, adolescents and young adults, but thereafter increased in DS compared to controls. Conclusions High levels of Aβ42 and tau in both young controls and DS suggest these proteins are produced by normal physiological processes, whereas, the changes seen in later life are consistent with emergence of pathological alterations. Our plasma biomarker results are in good agreement with prior neuropathology studies and indicate that the third and fourth decades (i.e. 20 to 40 years of age) of life are pivotal periods during which AD processes manifest in DS. Application of the assays used here to longitudinal studies of individuals with DS aged 20 to 50 years of age, should further validate the use of these biomarkers, and in time may allow identification and monitoring of people with DS best suited for treatment with emerging AD therapies.
Cell Cycle Activity Correlates with Increased Anti-Tumor Immunity in Diverse Cancers
Authors: Jiang Shanmei , He Yin , Li Mengyuan , Wang Xiaosheng 
Published: January 2020

Abstract
Objectives The cell cycle pathway regulating cell proliferation is overactivated in various cancers. Immune evasion is another important mechanism for tumor cell hyperproliferation. Nevertheless, the relationship between cell cycle and tumor immunity remains not fully understood. Materials and Methods Using the cancer genomics datasets for 10 cancer cohorts from the Cancer Genome Atlas (TCGA) program, we investigated the association between cell cycle activity (CCA) and anti-tumor immune signatures. We also explored the association between CCA and PD-L1 expression in these cancer cohorts. Moreover, we investigated the association between CCA and immunotherapy response in several cancer cohorts receiving immunotherapy. Results CCA likely exhibited positive associations with anti-tumor immune signatures (CD8+ T cell infiltration and immune cytolytic activity) in these cancer cohorts. The strong positive associations of CCA with DNA damage repair pathways and with tumor mutation load may explain the positive associations between CCA and anti-tumor immune signatures. Moreover, CCA displayed significant positive correlations with PD-L1 expression. Finally, we found that the enhanced CCA tended to be associated with unfavorable clinical outcomes in the TCGA cancer cohorts, though such association was not observed in the cancer cohorts receiving immune checkpoint blockade therapy. Conclusions CCA has significant positive associations with both anti-tumor immune signatures and tumor immune-suppressive signatures in diverse cancer types. Our findings provide new insights into cancer biology and potential clinical implications for cancer immunotherapy.
Closed Drainage versus Non-drainage for Single-level Lumbar Discectomy: a prospective randomized controlled study
Authors: Guo Hua , Ji Zhaohua , Gao Xi , Zhang Yuting , Yuan Li , Hao Dingjun , Wang Biao 
Published: January 2020

Abstract
Background In spine surgery, postoperative epidural hematoma and wound infections can have devastating neurologic compromise. Closed drainage is commonly used for prevention of postoperative hematoma, infection, and associated neurologic impairment after lumbar decompression, but it remains unclear whether closed drainage reduces postoperative complications and improves clinical outcomes or not. The purpose of this study was to determine the efficacy of closed drainage in reducing complications and improving clinical outcomes after single-level lumbar discectomy. Methods 420 patients with single-level lumbar disc herniation were recruited between March 2012 and March 2015 (169 females and 251 males, age 50.0±6.4 years). Patients were randomly assigned to either closed drainage group (214 patients) or non-drainage group (206 patients). The rates of postoperative complications (fever, symptomatic epidural hematoma, wound infections, and requiring revision surgery) were compared between the two groups using a chi square test or Fisher exact test. Pain intensity was evaluated by VAS. Functional ability was measured for all the patients using ODI. The lower extremity VAS score and ODI score were evaluated preoperatively, postoperatively, and at the last follow-up. The operation area VAS scores were evaluated preoperative, postoperative day 1, week 1, week 2, month 1, and at the last follow-up. The scoring results were compared between the two groups using a t test. Results The difference in postoperative fever between patients in the closed drainage group (18.7%) and non-drainage group (28.2%) was statistically significant ( p <0.05). This is mainly due to the difference of patients with fever less than 38.5 °C . There was no significant difference in symptomatic epidural hematoma, infection rate, and re-operation rate when the two groups were compared. Only compared the postoperative day 1 operation area VAS score, the closed drainage group (5.1±0.8) was better than the non-drainage group (6.0±0.7) and with a significant statistical difference ( p <0.05). The left scoring results compared between the two groups were not significant difference ( p >0.05). Conclusions We believe that closed drainage can be beneficial to reduce postoperative fever rate and alleviate postoperative operation area pain in the early postoperative period, but it has no effect on preventing postoperative occurrence of symptomatic epidural hematoma, wound infections, need for revision surgery; and improving clinical outcomes in single-level lumbar discectomy.
Effect of different land use systems and soil depths on soil chemical properties alteration in Yerer forests and its surrounding area, at the central highland of Ethiopia
Authors: Bato Yadesa , Bekele Tamrat , Demissew Sebsebe 
Published: January 2020

Abstract
Background Different land-use systems have different potentials to change soil chemical properties either positively or negatively. Hence, scientifically information on the soil chemical properties dynamics under different land-use systems is crucial for best land management practices, and to avoiding ecological negative impacts of it for sustainable development. The study aimed to evaluate the effect of different land-use systems and soil depths on selected soil chemical properties in Yerer forest and its surrounding area, central Ethiopia. The land-use systems included natural forest, four exotic tree plantation species (Eucalyptus globules, Cupressus lusitanica, Grevillea robusta, and Pinus patuala), grassland, grazing land, and agricultural cropland . Results The analysis of variance (ANOVA) for the majority of soil chemical properties of OC, TN, Avial. P, soil pH, EC, CEC, and exchangeable bases (Ca, Mg, K, Na) were showed that significant variations among land-use systems (P<0.0001). The highest mean values of OC (3.487% DM), TN (0.313% DM), Avail.P (31.515 mg/kg of soil), CEC (33.634 meq/100gm soil), Exch. Ca (17.126 cmol(+)/kg soil), Exch. Mg (5.369 cmol(+)/kg soil), and Exch. K (3.597 cmol(+)/kg soil) were observed under natural forest than others of land-use systems. The results also showed that the lowest mean values of OC (1.472% DM), TN (0.130%DM), soil pH (5.377), CEC (18.983 meq/100gm soil), Exch. Ca (9.931 cmol(+)/kg soil), Exch. K (1.197 cmol(+)/kg soil), and Exch. Na (0.206 cmol(+)/kg soil) were recorded under agricultural cropland than other land-use systems. The highest mean values of EC (3.474ds/m), and Exch. Na (0.604 cmol(+)/kg soil) were observed under Eucalyptus globules plantation forest. The overall mean values of OC, TN, Avail.P, CEC, Exch. Mg, Exch. Ca, Exch. K, and Exch. Na accumulation at the topsoil layer was higher than that of the subsoil layer except for soil pH and EC. Conclusion In general, the majority of soil chemical properties under agricultural cropland and Eucalyptus globules plantation forest were poorer than the soils subjected to other land-use systems which indicated that changes in land use system were significantly affected soil chemical properties.
Associated factors of poor treatment outcomes in patients with giant cell arteritis: clinical implication of large vessel lesions
Authors: Sugihara Takahiko , Hasegawa Hitoshi , Uchida Haruhito A , Yoshifuji Hajime , Watanabe Yoshiko , Amiya Eisuke , Maejima Yasuhiro , Konishi Masanori , Murakawa Yohko , Ogawa Noriyoshi , Furuta Shunsuke , Katsumata Yasuhiro , Komagata Yoshinori , Naniwa Taio , Okazaki Takahiro , Tanaka Yoshiya , Takeuchi Tsutomu , Nakaoka Yoshikazu , Arimura Yoshihiro , Harigai Masayoshi , Isobe Mitsuaki 
Published: January 2020

Abstract
Background: Relapses frequently occur in giant cell arteritis (GCA) patients treated with conventional immunosuppressive therapy, and identification of associated factors with poor treatment outcomes is relevant to adjust treatment appropriately. Methods: We enrolled 139 newly-diagnosed GCA patients treated with glucocorticoids between 2007 and 2014 in a retrospective, multi-center registry. Patients were diagnosed as having GCA with temporal artery biopsy, large-vessel lesions (LVLs) detected by imaging, 1990 American College of Rheumatology classification criteria, or combination of these. Poor treatment outcomes (non-achievement of clinical remission by week 24 or relapse during 52 weeks) were evaluated. Clinical remission was defined as absence of clinical signs and symptoms in cranial and large-vessel areas, polymyalgia rheumatica (PMR), and elevation of C-reactive protein (CRP) levels. A patient was determined to have relapse if he/she had either one of the signs and symptoms that newly appeared or worsened after achieving clinical remission. Re-elevation of CRP without clinical manifestations was considered as relapse if other causes such as infection were excluded and the treatment was intensified. Associated factors with poor treatment outcomes were analyzed by using the Cox proportional hazard model.Results: Cranial lesions, PMR, and LVLs were detected in 77.7%, 41.7%, and 52.5% of the enrolled patients, respectively. Treatment outcomes were evaluated in 119 newly-diagnosed patients who were observed for 24 weeks or longer. The mean initial dose of prednisolone was 0.76 mg/kg/day, and 29.4% received any concomitant immunosuppressive drugs at baseline. Overall, 41 (34.5%) of the 119 patients had poor treatment outcomes; 13 did not achieve clinical remission by week 24, and 28 had relapse after achieving clinical remission. Cumulative rates of the events of poor treatment outcomes in patients with and without LVLs were 47.5 % and 17.7%, respectively. A multivariable model showed the presence of LVLs at baseline was significantly associated with poor treatment outcomes (adjusted hazard ratio [HR] 3.54, 95% CI 1.52-8.24, p=0.003). Cranial lesions and PMR did not increase the risk of poor treatment outcomes. Conclusion: Presence of LVLs detected by imaging at baseline was an associated factor for poor treatment outcomes in patients given conventional immunosuppressive therapy without biologics.