bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-targeted nanoparticles improve the therapeutic index of BCL2 and MCL1 dual inhibition
Authors: Bala Tannan Neeta , Manzari Mandana T. , Herviou Laurie , Da Silva Ferreira Mariana , Hagen Connor , Kiguchi Hiroto , Manova-Todorova Katia , Seshan Venkatraman , de Stanchina Elisa , Heller Daniel A. , Younes Anas 
Published: October 2020

AbstractCancer and normal cells use multiple antiapoptotic BCL2 proteins to prevent cell death. Therapeutic targeting of multiple BCL2 family proteins enhances tumor killing but is also associated with increased systemic toxicity. Here, we demonstrate that the dual targeting of MCL1 and BCL2 proteins using the small molecules S63845 and venetoclax induces durable remissions in mice that harbor human diffuse large B-cell lymphoma (DLBCL) tumors but is accompanied by hematologic toxicity and weight loss. To mitigate these toxicities, we encapsulated S63845 or venetoclax into nanoparticles that target P-selectin, which is enriched in tumor endothelial cells. In vivo and ex vivo imaging demonstrated preferential targeting of the nanoparticles to lymphoma tumors over vital organs. Mass spectrometry analyses after administration of nanoparticle drugs confirmed tumor enrichment of the drug while reducing plasma levels. Furthermore, nanoparticle encapsulation allowed 3.5- to 6.5-fold reduction in drug dose, induced sustained remissions, and minimized toxicity. Our results support the development of nanoparticles to deliver BH3 mimetic combinations in lymphoma and in general for toxic drugs in cancer therapy.
The influence of active and passive air humidification on exhaled breath condensate volume
Authors: Hjembaek-Brandt Jeppe , Hindborg Mathias , Jensen Andreas K. , Dalby Sørensen Christian Ari , Rasmussen Bodil Steen , Maltesen Raluca Georgiana , Bestle Morten Heiberg 
Published: October 2020

Exhaled breath condensate (EBC) is safely collected in mechanically ventilated (MV) patients, but there are no guidelines regarding humidification of inhaled air during EBC collection. We investigated the influence of active and passive air humidification on EBC volumes obtained from MV patients.We collected 29 EBC samples from 21 critically ill MV patients with one condition of active humidification and four different conditions of non-humidification; 19 samples from 19 surgical MV patients with passive humidification and two samples from artificial lungs MV with active humidification. The main outcome was the obtained EBC volume per 100 L exhaled air.When collected with different conditions of non-humidification, mean [95% CI] EBC volumes did not differ significantly (1.35 [1.23; 1.46]versus1.16 [1.05; 1.28]versus1.27 [1.13; 1.41]versus1.17 [1.00; 1.33] mL/100 L, p=0.114). EBC volumes were higher with active humidification than with non-humidification (2.05 [1.91; 2.19]versus1.25 [1.17; 1.32] mL/100 L, p<0.001). The volume difference between these corresponded to the EBC volume obtained from artificial lungs (0.81 [0.62; 0.99]versus0.89 mL/100 L, p=0.287). EBC volumes were lower for surgical MV patients with passive humidification compared to critically ill MV patients with non-humidification (0.55 [0.47; 0.63]versus1.25 [1.17; 1.32] mL/100 L, p<0.001).While active humidification increases EBC volumes, passive humidification decreases EBC volumes and possibly influences EBC composition by other mechanisms. We propose that EBC should be collected from MV patients without air humidification to improve reproducibility and comparability across studies, and that humidification conditions should always be reported.
Selection and application of trophic magnification factors for priority substances to normalize freshwater fish monitoring data under the European Water Framework Directive: a case study
Authors: Rüdel Heinz , Kosfeld Verena , Fliedner Annette , Radermacher Georg , Schlechtriem Christian , Duffek Anja , Rauert Caren , Koschorreck Jan 
Published: October 2020

Abstract
Background
The European Water Framework Directive (WFD) requires the monitoring of biota—preferably fish—to check the compliance of tissue concentrations of priority substances (PS) against substance-specific environmental quality standards (EQSs). In monitoring programs, different fish species are covered, which often are secondary consumers with a trophic level (TL) of about 3. For harmonization, a normalization of monitoring data to a common trophic level is proposed, i.e., TL 4 (predatory fish) in freshwaters, so that data would be sufficiently protective. For normalization, the biomagnification properties of the chemicals can be considered by applying substance-specific trophic magnification factors (TMFs). Alternatively, TL-corrected biomagnification factors (BMFTLs) may be applied. Since it is impractical to derive site-specific TMFs or BMFTLs, often data from literature will be used for normalization. However, available literature values for TMFs and BMFTLs are quite varying. In the present study, the use of literature-derived TMFs and BMFTLs in data normalization is studied more closely.

Results
An extensive literature evaluation was conducted to identify appropriate TMFs for the WFD PS polybrominated diphenyl ethers (PBDE), hexachlorobenzene, perfluorooctane sulfonate (PFOS), dioxins and dioxin-like compounds (PCDD/F + dl-PCB), hexabromocyclododecane, and mercury. The TMFs eventually derived were applied to PS monitoring data sets of fish from different trophic levels (chub, bream, roach, and perch) from two German rivers. For comparison, PFOS and PBDE data were also normalized using literature-retrieved BMFTLs.

Conclusions
The evaluation illustrates that published TMFs and BMFTLs for WFD PS are quite variable and the selection of appropriate values for TL 4 normalization can be challenging. The normalized concentrations partly included large uncertainties when considering the range of selected TMFs, but indicated whether an EQS exceedance at TL 4 can be expected. Normalization of the fish monitoring data revealed that levels of substances accumulating in the food web (TMF or BMF > 1) can be underestimated when relying on fish with TL < 4 for EQS compliance assessment. The evaluation also revealed that TMF specifically derived for freshwater ecosystems in Europe would be advantageous. Field-derived BMFTLs seemed to be no appropriate alternative to TMFs, because they can vary even stronger than TMFs.
miR168 targets Argonaute1A mediated miRNAs regulation pathways in response to potassium deficiency stress in tomato
Authors: Liu Xin , Tan Chunchang , Cheng Xin , Zhao Xiaoming , Li Tianlai , Jiang Jing 
Published: October 2020

Abstract
Background
Potassium (K+) is an essential ion for most plants, as it is involved in the regulation of growth and development. K+ homeostasis in plant cells has evolved to facilitate plant adaptation to K+-deficiency stress. Argonaute1 (AGO1) is regulated by miR168 to modulate the small RNA regulatory pathway by RNA silencing complex (RISC) in tomatoes. However, the role of miR168-mediated regulation of AGO1 in the context of K+ deficiency stress in tomatoes has not been elucidated yet.

Results
SlmiR168 and its target gene SlAGO1A were differentially expressed among low-K+-tolerant JZ34 and low-K+-sensitive JZ18 tomato plants. Transgenic tomato plants constitutively expressing pri-SlmiR168a showed stronger root system growth, better leaves development, and higher K+ contents in roots under K+-deficiency stress than those of the transgenic tomato lines expressing rSlAGO1A (SlmiR168-resistant) and the wild type (WT). Deep sequencing analysis showed that 62 known microRNAs (miRNAs) were up-regulated in 35S:rSlAGO1 compared with WT tomatoes. The same miRNAs were down-regulated in 35S:SlmiR168a compared with WT plants. The integrated analysis found 12 miRNA/mRNA pairs from the 62 miRNAs, including the root growth and cytokinin (CTK)/abscisic acid (ABA) pathways.

Conclusions
The regulation mediated by SlmiR168 of SlAGO1A contributes to the plant development under low-K+ stress. Moreover, this regulation mechanism may influence downstream miRNA pathways in response to low-K+ stress through the CTK/ABA and root growth modulation pathways.
Evaluation of alveolar recruitment maneuver on respiratory resistance during general anesthesia: a prospective observational study
Authors: Nakahira Junko , Nakano Shoko , Minami Toshiaki 
Published: October 2020

AbstractBackgroundAlveolar recruitment maneuvers enable easily reopening nonaerated lung regions via a transient elevation in transpulmonary pressure. To evaluate the effect of these maneuvers on respiratory resistance, we used an oscillatory technique during mechanical ventilation. This study was conducted to assess the effect of the alveolar recruitment maneuvers on respiratory resistance under routine anesthesia. We hypothesized that respiratory resistance at 5 Hz (R5) after the maneuver would be decreased after the lung aeration.MethodsAfter receiving the ethics committee’s approval, we enrolled 33 patients who were classified with an American Society of Anesthesiologists physical status of 1, 2 or 3 and were undergoing general anesthesia for transurethral resection of a bladder tumor within a 12-month period from 2017 to 2018. The recruitment maneuver was performed 30 min after endotracheal intubation. The maneuver consisted of sustained manual inflation of the anesthesia reservoir bag to a peak inspiratory pressure of 40 cmH2O for 15 s, including 5 s of gradually increasing the peak inspiratory pressure. Respiratory resistance was measured using the forced oscillation technique before and after the maneuver, and the mean R5 was calculated during the expiratory phase. The respiratory resistance and ventilator parameter results were analyzed using paired Student’st-tests, andp < 0.05 was considered statistically significant.ResultsWe analyzed 31 patients (25 men and 6 women). R5 was 7.3 ± 1.6 cmH2O/L/sec before the recruitment maneuver during mechanical ventilation and was significantly decreased to 6.4 ± 1.7 cmH2O/L/sec after the maneuver. Peak inspiratory pressure and plateau pressure were significantly decreased, and pulmonary compliance was increased, although the values were not clinically relevant.ConclusionThe recruitment maneuver decreased respiratory resistance and increased lung compliance during mechanical ventilation.Trial registrationName of registry: Japan Medical Association Center for Clinical Trials.Trial registration number: reference JMA-IIA00136.Date of registration: 2 September 2013.URL of trial registry record:https://dbcentre3.jmacct.med.or.jp/JMACTR/App/JMACTRE02_04/JMACTRE02_04.aspx?kbn=3&seqno=3582
Challenging oneself on the threshold to the world of research – frail older people’s experiences of involvement in research
Authors: Berge Isak , Barenfeld Emmelie , Dahlin-Ivanoff Synneve , Haak Maria , Lood Qarin 
Published: October 2020

AbstractBackgroundUser involvement of people outside academia in research is argued to increase relevance of research for society and to empower the involved lay persons. Frail older people can be a hard to reach group for research and thus an underrepresented group in research. There is a lack of knowledge how collaboration with frail older people should be best performed. Therefore, the aim of this study was to explore frail older people’s experiences of involvement in research.MethodsIn this study we have invited people, 75 years of age or older screened as physically frail and who have previously participated in a study as data sources, to share their experiences by intensive interviewing. Data was collected and analysed in parallel inspired by a constructivist grounded theory approach.ResultsThe results demonstrate how frail older people have different incentives, how their context of ageing and the unusual position of being involved in research altogether influenced how, where and in what way they wished to be involved in research. This is described in three categories:Contributing to making a difference for oneself and others, Living a frail existenceandBeing on somebody else’s turf.The categories compose the core category,Challenging oneself on the threshold to the world of research, which symbolises the perceived distance between the frail older people themselves and the research world, but also the challenges the frail older people could go through when choosing to be involved in research.ConclusionsFrail older people have a varied capacity to participate in research, but in what way and how is difficult to know before they have been involved in the process of research. Our results advocate that it is problematic to exclude frail older people a priori and that there is a potential for new perspectives and knowledge to be shaped in the encounter and in the relationship between the researcher and the frail older person. For research to be able to cater for frail older people’s needs of health services, their voices need to be heard and taken into consideration.
Traumatic brain injury—the effects of patient age on treatment intensity and mortality
Authors: Skaansar Ola , Tverdal Cathrine , Rønning Pål Andre , Skogen Karoline , Brommeland Tor , Røise Olav , Aarhus Mads , Andelic Nada , Helseth Eirik 
Published: October 2020

Abstract
Background
Ageing is associated with worse treatment outcome after traumatic brain injury (TBI). This association may lead to a self-fulfilling prophecy that affects treatment efficacy. The aim of the current study was to evaluate the role of treatment bias in patient outcomes by studying the intensity of diagnostic procedures, treatment, and overall 30-day mortality in different age groups of patients with TBI.

Methods
Included in this study was consecutively admitted patients with TBI, aged ≥ 15 years, with a cerebral CT showing intracranial signs of trauma, during the time-period between 2015–2018. Data were extracted from our prospective quality control registry for admitted TBI patients. As a measure of management intensity in different age groups, we made a composite score, where placement of intracranial pressure monitor, ventilator treatment, and evacuation of intracranial mass lesion each gave one point. Uni- and multivariate survival analyses were performed using logistic multinomial regression.

Results
A total of 1,571 patients with TBI fulfilled the inclusion criteria. The median age was 58 years (range 15–98), 70% were men, and 39% were ≥ 65 years. Head injury severity was mild in 706 patients (45%), moderate in 437 (28%), and severe in 428 (27%). Increasing age was associated with less management intensity, as measured using the composite score, irrespective of head injury severity. Multivariate analyses showed that the following parameters had a significant association with an increased risk of death within 30 days of trauma: increasing age, severe comorbidities, severe TBI, Rotterdam CT-score ≥ 3, and low management intensity.

Conclusion
The present study indicates that the management intensity of hospitalised patients with TBI decreased with advanced age and that low management intensity was associated with an increased risk of 30-day mortality. This suggests that the high mortality among elderly TBI patients may have an element of treatment bias and could in the future be limited with a more aggressive management regime.
Inducing multiple antibodies to treat squamous cell esophageal carcinoma
Authors: Hoshino Isamu , Nabeya Yoshihiro , Takiguchi Nobuhiro , Gunji Hisashi , Ishige Fumitaka , Iwatate Yosuke , Kuwajima Akiko , Shiratori Fumiaki , Okada Rei , Shimada Hideaki 
Published: October 2020

Abstract
Background
The positive response and the clinical usefulness of 14 serum antibodies in patients with esophageal squamous cell carcinoma (ESCC) were examined in this study. The Cancer Genome Atlas (TCGA) was used to investigate the frequency of gene expressions, mutations, and amplification of these 14 antigens and also the possible effects of antibody induction.

Methods
Blood serum derived from 85 patients with ESCC was collected and analyzed for the 14 antibodies using ELISA. The prognosis between positive and negative antibodies were then compared. The antibody panel included LGALS1, HCA25a, HCC-22-5, and HSP70.

Results
Patient serum was positive for all antibodies, except VEGF, with the positive rates ranging from 1.18 to 10.59%. Positive rates for LGALS1, HCA25a, HCC-22-5, and HSP70 were > 10%. TCGA data revealed that all antigen-related genes had little or no mutation or amplification, and hence an increase in gene expression affected antibody induction. The positive results from the panel accounted for the positive rate comparable to the combination of CEA and SCC. No significant association was observed between the presence of antibodies and disease prognosis.

Conclusions
The detection rates of LGALS1, HCA25a, HCC-22-5, and HSP70 were 10% higher in patients with ESCC. Gene overexpression may be involved in such antibody production. These four antibodies were applied as a panel in comparison with conventional tumor markers. Moreover, it was confirmed that the combination of this panel and the conventional tumor markers significantly improved the positive rate.
Knowledge, attitude and practice towards tuberculosis in Gambia: a nation-wide cross-sectional survey
Authors: Bashorun Adedapo Olufemi , Linda Christopher , Omoleke Semeeh , Kendall Lindsay , Donkor Simon D. , Kinteh Ma-Ansu , Danso Baba , Leigh Lamin , Kandeh Sheriff , D’Alessandro Umberto , Adetifa Ifedayo Morayo O. 
Published: October 2020

Abstract
Background
Early diagnosis and treatment of tuberculosis (TB) are the mainstay of global and national TB control efforts. However, the gap between expected and reported cases persists for various reasons attributable to the TB services and care-seeking sides of the TB care cascade. Understanding individual and collective perspectives of knowledge, attitudes, beliefs and other social circumstances around TB can inform an evidence-based approach in engaging communities and enhance their participation in TB case detection and treatment.

Methods
The study was conducted during the Gambian survey of TB prevalence. This was a nationwide cross-sectional multistage cluster survey with 43,100 participants aged ≥15 years in 80 clusters. The study sample, a random selection of 10% of the survey population within each cluster responded to a semi-structured questionnaire administered by trained fieldworkers to assess the knowledge, attitudes and practice of the participants towards TB. Overall knowledge, attitude and practice scores were dichotomised using the computed mean scores and analysed using descriptive, univariable and multivariable logistic regression.

Results
All targeted participants (4309) were interviewed. Majority were females 2553 (59.2%), married 2614 (60.7%), had some form of education 2457 (57%), and were unemployed 2368 (55%). Although 3617 (83.9%) of the participants had heard about TB, only 2883 (66.9%) were considered to have good knowledge of TB. Overall 3320 (77%) had unfavourable attitudes towards TB, including 1896 (44%) who indicated a preference for staying away from persons with TB rather than helping them. However, 3607(83.7%) appeared to have the appropriate health-seeking behaviours with regard to TB as 4157 (96.5%) of them were willing to go to the health facility if they had symptoms suggestive of TB.

Conclusions
About 3 in 10 Gambians had poor knowledge on TB, and significant stigma towards TB and persons with TB persists. Interventions to improve TB knowledge and address stigma are required as part of efforts to reduce the burden of undiagnosed TB in the country.
Potential research ethics violations against an indigenous tribe in Ecuador: a mixed methods approach
Authors: Ortiz-Prado Esteban , Simbaña-Rivera Katherine , Gómez-Barreno Lenin , Tamariz Leonardo , Lister Alex , Baca Juan Carlos , Norris Alegria , Adana-Diaz Lila 
Published: October 2020

Abstract
Background
Biomedical and ethnographic studies among indigenous people are common practice in health and geographical research. Prior health research misconduct has been documented, particularly when obtaining genetic material. The objective of this study was to crossmatch previously published data with the perceptions of the Waorani peoples about the trading of their genetic material and other biological samples.

Methods
We conducted a mixed methods study design using a tailored 15-item questionnaire in 72 participants and in-depth interviews in 55 participants belonging to 20 Waorani communities about their experiences and perceptions of participating in biomedical research projects. Additionally, we conducted a systematic review of the literature in order to crossmatch the published results of studies stating the approval of an ethics committee and individual consent within their work.

Results
A total of 40 men (60%) and 32 women (40%), with a mean age of 57 ± 15 years agreed to be interviewed for inclusion. Five main categories around the violation of good clinical practices were identified, concerning the obtention of blood samples from a recently contacted Waorani native community within the Amazonian region of Ecuador. These themes are related to the lack of adequate communication between community members and researchers as well as the voluntariness to participate in health research. Additionally, over 40 years, a total of 38 manuscripts related to the use of biological samples in Waorani indigenous people were published. The majority of the studies (68%) did not state within their article obtaining research ethics board approval, and 71% did not report obtaining the informed consent of the participants prior to the execution of the project.

Conclusion
Clinical Research on the Waorani community in the Ecuadorian Amazon basin has been performed on several occasions. Unfortunately, the majority of these projects did not follow the appropriate ethical and professional standards in either reporting the results or fulfilling them. The results of our investigation suggest that biological material, including genetic material, has been used by researchers globally, with some omitting the minimum information required to guarantee transparency and good clinical practices. We highlight the importance of stating ethics within research to avoid breaches in research transparency.