bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel insight into the regulatory roles of diverse RNA modifications: Re-defining the bridge between transcription and translation
Authors: Shi Hanhan , Chai Peiwei , Jia Renbing , Fan Xianqun 
Published: April 2020

AbstractRNA modifications can be added or removed by a variety of enzymes that catalyse the necessary reactions, and these modifications play roles in essential molecular mechanisms. The prevalent modifications on mRNA include N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 5-hydroxymethylcytosine (hm5C), pseudouridine (Ψ), inosine (I), uridine (U) and ribosemethylation (2’-O-Me). Most of these modifications contribute to pre-mRNA splicing, nuclear export, transcript stability and translation initiation in eukaryotic cells. By participating in various physiological processes, RNA modifications also have regulatory roles in the pathogenesis of tumour and non-tumour diseases. We discussed the physiological roles of RNA modifications and associated these roles with disease pathogenesis. Functioning as the bridge between transcription and translation, RNA modifications are vital for the progression of numerous diseases and can even regulate the fate of cancer cells.
Exploring the barriers and facilitators to the acceptability of donor human milk in eastern Uganda – a qualitative study
Authors: Magowan Sarah , Burgoine Kathy , Ogara Collin , Ditai James , Gladstone Melissa 
Published: April 2020

Abstract
Background
Human milk is the best nutrition for all infants. When the mother’s own milk is not available, the World Health Organization recommends the use of donated human milk and milk banking for neonates born prematurely or with medical problems.
Donor human milk is rarely available in low-resource settings where both the rates of preterm birth and neonatal mortality are highest. The potential to reduce neonatal mortality through use of donated human milk is one that is yet to be fully explored in the African setting. For the introduction of any new health intervention to be successful, determining the barriers and facilitators to its acceptability is a vital first step. There are limited studies on this in sub-Saharan Africa.

Methods
This qualitative study used focus group discussions and in-depth interviews to explore the potential barriers and facilitators to utilizing donated human milk for neonates in a hospital setting in eastern Uganda from the perspectives of caregivers (parents, grandparents) and healthcare workers.

Results
Six focus group discussions involving 28 caregivers were conducted in a hospital setting in eastern Uganda. Four in-depth interviews were then also held with healthcare staff. Lack of knowledge of donated human milk emerged with discussants, and the barriers relating to transmission of infection (HIV) and poor hygiene. Common reasons which facilitated its acceptability were; a general knowledge and recognition that human milk is better than formula milk and a strong belief by caregivers in healthcare workers providing knowledgeable and safe care. Healthcare workers were supportive of introducing donor human milk but perceived a need for community and hospital education programs to enable this to be facilitated and scaled up.

Conclusions
This study shows that donor human milk can be acceptable to the caregivers of vulnerable babies in hospital settings in Uganda. Lack of awareness of donor human milk, its benefits and the methods of screening, acquisition and storage of donor milk are all barriers that could be addressed through improved education. This study advocates for national policies and programs that build capacity for effective and sustainable donor milk banking.
Sex-specific associations with cerebrospinal fluid biomarkers in dementia with Lewy bodies
Authors: van de Beek M. , Babapour Mofrad R. , van Steenoven I. , Vanderstichele H. , Scheltens P. , Teunissen C. E. , Lemstra A. W. , van der Flier W. M. 
Published: April 2020

Abstract
Background
Dementia with Lewy bodies (DLB) is more prevalent in men than in women. In addition, post-mortem studies found sex differences in underlying pathology. It remains unclear whether these differences are also present antemortem in in vivo biomarkers, and whether sex differences translate to variability in clinical manifestation. The objective of this study was to evaluate sex differences in cerebrospinal fluid (CSF) biomarker concentrations (i.e., alpha-synuclein (α-syn), amyloid β1-42 (Aβ42), total tau (Tau), phosphorylated tau at threonine 181 (pTau)) and clinical characteristics in DLB.

Methods
We included 223 DLB patients from the Amsterdam Dementia Cohort, of which 39 were women (17%, age 70 ± 6, MMSE 21 ± 6) and 184 men (83%, age 68 ± 7, MMSE 23 ± 4). Sex differences in CSF biomarker concentrations (i.e., α-syn, Aβ42, Tau, and pTau) were evaluated using age-corrected general linear models (GLM). In addition, we analyzed sex differences in core clinical features (i.e., visual hallucinations, parkinsonism, cognitive fluctuations, and REM sleep behavior disorder (RBD) and cognitive test scores using age- and education-adjusted GLM.

Results
Women had lower CSF α-syn levels (F 1429 ± 164 vs M 1831 ± 60, p = 0.02) and CSF Aβ42 levels (F 712 ± 39 vs M 821 ± 18, p = 0.01) compared to men. There were no sex differences for (p) Tau concentrations (p > 0.05). Clinically, women were older, had a shorter duration of complaints (F 2 ± 1 vs M 4 ± 3, p < 0.001), more frequent hallucinations (58% vs 38%, p = 0.02), and scored lower on MMSE and a fluency task (MMSE, p = 0.02; animal fluency, p = 0.006). Men and women did not differ on fluctuations, RBD, parkinsonism, or other cognitive tests.

Conclusions
Women had lower Aβ42 and α-syn levels than men, alongside a shorter duration of complaints. Moreover, at the time of diagnosis, women had lower cognitive test scores and more frequent hallucinations. Based on our findings, one could hypothesize that women have a more aggressive disease course in DLB compared to men. Future research should investigate whether women and men with DLB might benefit from sex-specific treatment strategies.
Protocol for a double-blind, randomized controlled trial on the dose-related efficacy of omalizumab in multi-food oral immunotherapy
Authors: Langlois Alexandra , Lavergne Marie-Hélène , Leroux Hélène , Killer Kerstin , Azzano Pauline , Paradis Louis , Samaan Kathryn , Lacombe-Barrios Jonathan , Eiwegger Thomas , Upton Julia , Sussman Gordon , Poder Thomas , Mâsse Benoît , Des Roches Anne , Bégin Philippe 
Published: April 2020

AbstractBackgroundPrevious proof-of-concept studies have shown that a short course of omalizumab can safely accelerate the oral immunotherapy schedule for multiple allergens simultaneously. Considering the high cost of medication, the dose-related efficacy of omalizumab at decreasing the duration of oral immunotherapy up-dosing phase must be objectively quantified before cost–benefit analyses can be performed. The primary objective of this trial will be to compare the efficacy of 2 omalizumab dosages to placebo at decreasing time-to-maintenance dose during a symptom-driven multi-food OIT protocol.MethodsA total of 90 participants aged 6 to 25 with multiple food allergies (3 or more) will be enrolled at four sites in Canada. Participants will be randomized to: (A) Omalizumab 8 mg/kg per month (n = 36); (B) Omalizumab 16 mg/kg per month (n = 36); or (C) Placebo (n = 18). Study drug will be administered at full dosage for 12 weeks, then progressively tapered at 50% dosage (8 mg/kg vs 4 mg/kg vs placebo) for 4 weeks and at 25% dosage (4 mg/kg vs 2 mg/kg vs placebo) for another 4 weeks. After a pre-treatment period of 8 weeks, participants will undergo an initial food escalation (IFE) to an OIT mix containing 3 allergens and start daily home dosing with biweekly increases until a target daily maintenance of 1500 mg protein is achieved. The amount escalated at each visit will vary based on treatment tolerance according to a standardized up-dosing algorithm. Participants will be followed for at least 12 months following the initial food escalation. The primary endpoint will be time from IFE to the target maintenance dose of 1500 mg protein. Time-to-event analytic methods, including the log-rank test, will be used to compare the 3 arms.DiscussionThis trial uses a novel pragmatic approach to compare OIT with omalizumab to OIT without omalizumab in a blinded manner, which allows to single out the effect of this anti-IgE medication on treatment effectiveness speed without the recourse to predetermined schedules. The innovative patient-centered up-dosing algorithm allows to maximise treatment effectiveness speed without compromising patient safety, regardless of whether the patient is on omalizumab or not. This study will also provide novel prospective data to inform on the optimal and most cost-effective dosage for this indication.Trial registration ClinicalTrials.gov, NCT04045301, Registered 5 August 2019,https://clinicaltrials.gov/ct2/show/NCT04045301
Melioidosis after a long silence in Sri Lanka: an environmental hazard and dilemma in diagnosis, with recovery and longitudinal follow-up for 13 years: a case report
Authors: Pathirage Manoji M. K. , Kularatne Senanayake A. M. , Weerakoon Kosala G. 
Published: April 2020

Abstract
Background
Melioidosis is a potentially fatal bacterial infection caused by Burkholderia pseudomallei. The existence of melioidosis in Sri Lanka was once unheard of, and entertaining it as a diagnosis in clinical practice was extremely rare.

Case presentation
In this case report, we describe the clinical, epidemiological, and longitudinal follow-up data of a 58-year-old previously healthy Sinhalese woman who presented to our hospital with protracted febrile illness of 5 weeks’ duration, later developing multiple abscesses at different sites of the body. There was a significant delay in confirming the diagnosis of melioidosis by isolating B. pseudomallei from blood and pus cultures. The patient recovered fully with a prolonged course of antibiotics and has remained in good health over the last 13 years without recurrence. Despite being immunocompetent, she had contracted the infection by a brief contact with mud soil in a footpath.

Conclusions
A high index of clinical suspicion along with laboratory support is needed to confirm the diagnosis of melioidosis. Treatment with sensitive antibiotics over a long duration is needed, and longitudinal follow-up is essential to detect recurrences. This case raised awareness and created renewed interest in studies of melioidosis in Sri Lanka.
A Filon-like integration strategy for calculating exact exchange in periodic boundary conditions: a plane-wave DFT implementation
Authors: Bylaska Eric J , Waters Kevin , Hermes Eric D , Zádor Judit , Rosso Kevin M 
Published: April 2020

AbstractAn efficient and accurate approach for calculating exact exchange and other two-electron integrals has been developed for periodic electronic structure methods. Traditional approaches used for integrating over the Brillouin zone in band structure calculations, e.g. trapezoidal or Monkhorst-Pack, are not accurate enough for two-electron integrals. This is because their integrands contain multiple singularities over the double integration of the Brillouin zone, which with simple integration methods lead to very inaccurate results. A common approach to this problem has been to replace the Coulomb interaction with a screened Coulomb interaction that removes singularities from the integrands in the two-electron integrals, albeit at the inelegance of having to introduce a screening factor which must precomputed or guessed. Instead of introducing screened Coulomb interactions in an ad hoc way, the method developed in this work derives an effective screened potential using a Filon-like integration approach that is based only on the lattice parameters. This approach overcomes the limitations of traditionally defined screened Coulomb interactions for calculating two-electron integrals, and makes chemistry many-body calculations tractable in periodic boundary conditions. This method has been applied to several systems for which conventional DFT methods do not work well, including the reaction pathways for the addition of H2 to phenol and Au$_{20}^{-}$20− nanoparticle, and the electron transfer of a charge trapped state in the Fe(II) containing mica, annite.
Phase I trial of dacarbazine and bortezomib in melanoma and soft tissue sarcoma
Authors: Roberts J. D. , Ernstoff M. S. , Birdsell C. 
Published: April 2020

18008 Background: Dacarbazine (D) has modest single agent activity against melanoma and soft tissue sarcomas. NFκB is a transcription factor that in general promotes cell survival and antagonizes apoptosis. In melanoma NFκB is constitutively activated and increases further in response to D. Bortezomib (B) is a prosteasome inhibitor that down-regulates NFκB. In tissue culture and xenograft melanoma models B potentiates anticancer effects of D and the related agent temozolomide. Methods: The primary objective is to identify recommended phase II doses for D+B administered weekly. Patients with advanced melanoma or sarcoma are enrolled in a traditional ‘3+3‘ dose escalation format. Results: Recommended phase II doses will be at least D 250 mg/m2 and B 1.6 mg/m2, and dose escalation continues. Treatment has been generally well tolerated with known D and B toxicities. Among 8 melanoma patients there is 1 partial response (PR), 1 with stable disease on treatment 15 weeks, 6 with progressive disease (PD) 6, 7, 8, 8, 13, and 13 weeks. Among 5 sarcoma patients there is 1 PR and 4 with PD 4, 8, 16, and 24 wks. Conclusions: At full dose B and moderate dose D for this schedule, D+B is feasible and generally well-tolerated. Activity beyond that of D alone is not apparent to date, but several or all patients have been treated at less than maximum tolerated doses. [Table: see text]
Long-term disease-free survival (LTDFS) after biochemotherapy (BioCT) for stage IV melanoma: The experience of the Hospital Sírio-Libanês, Brazil
Authors: William W. N. , Schmerling R. A. , Belfort F. A. , Fonseca H. E. , Buzaid A. C. 
Published: April 2020

18013 Background: A small subset of patients with metastatic melanoma treated with BioCT may experience LTDFS. Methods: We retrospectively reviewed all patients with stage IV melanoma and a follow-up of at least 12 months (mo) who received BioCT between 1/1998 -1/2005 under the supervision of one of the co-authors (ACB). Treatment consisted of two 3-week-cycles of cisplatin 25 mg/m2 IV D1–3, vinblastine 2 mg/m2 IV D1–3, dacarbazine 800 mg/m2 IV D1, IL-2 9 MIU/m2 IVCI D1–4, and interferon alpha-2b (IFN) 5 MIU SC D1–5. Responding patients received up to 4 additional cycles, depending on tolerance. Metastasectomy was performed for residual disease at the discretion of the attending physician. Results: A total of 57 pts (36 men, median age 45 years, median follow-up 50 months) received 190 cycles of BioCT (median 3 cycles/pt). No deaths occurred during treatment. To date, 48 pts (84%) have recurred and 41 pts (72%) have died. Median time to progression and overall survival were 8 and 17 mo, respectively. Response rates using RECIST: CR 19%, PR 32%, for an overall response rate of 51%. LTDFS, defined as pts alive and recurrence-free at 24+ mo after BioCT, was observed in 8 of the 57 pts treated (29+, 30+, 51+, 58+, 69+, 71+, 80+, and 97+ mo). 4 of the 8 pts were rendered disease-free by surgery following BioCT (2 CR, 1 PR and 1 SD; 3 with viable melanoma at pathology and 1 with pathologic CR). The remaining 4 pts achieved CR and LTDFS with BioCT alone (see Table for clinical characteristics). Conclusions: LTDFS can be achieved in approximately 7% of pts with stage IV melanoma treated with BioCT alone. Although small, this subset of pts justifies the use of BioCT for young and highly selected pts. Further studies such as gene profiling designed to better identify individuals who could potentially benefit most from BioCT are clearly warranted. [Table: see text] No significant financial relationships to disclose.
Tuning formulation of multipeptide vaccination for melanoma patients at high risk of relapse
Authors: Baurain J. , Van Baren N. , Marchand M. , Humblet Y. , Machiels J. , Coulie P. G. 
Published: April 2020

18014 Background: Vaccination with MAGE peptides is followed by tumor regression in 10–20% of metastatic melanoma patients with detectable disease, mostly those with only SC or lymph node metastases. Anti-vaccine cytolytic T lymphocyte (CTL) responses have been observed in about 50% of the regressor patients, suggesting that these vaccines were poorly immunogenic. Recent reports have documented convincing CTL responses in patients vaccinated with peptides administered in a water-in-oil emulsion with Montanide, a clinical grade incomplete Freund’s adjuvant. After SC injection, this vaccine stimulates a local inflammation which could help to the recruitment of peptide presenting cells. Considering the absence of an effective treatment to prevent relapses of cutaneous melanoma, we applied this vaccination modality in an adjuvant setting. Methods and Results: We vaccinated 14 HLA-A2 melanoma patients with no evidence of disease but at high risk of relapse, with 4 antigenic peptides (MAGE-3.A2, NA17.A2, Tyrosinase.A2 and gp100.A2) emulsified in Montanide ISA51. Seven patients received 5 vaccinations, every 3 weeks, consisting of 4 injections of 900 μg of one peptide and 1 ml Montanide. Seven other patients received the same vaccines but with 300 μg of each peptide. Toxicity was limited to grade II, at the injection sites. Two thirds of the patients mounted a CTL response to peptide gp100.A2, and 50% to peptide NA17.A2. The lower doses of peptides were as immunogenic as the higher. Conclusions: These encouraging results indicate that this simple vaccination modality is not toxic and clearly immunogenic. We wish to formally assess the role of the immunological adjuvant Montanide in these CTL responses by vaccinating a third group of patients with the same 4 antigenic peptides without Montanide. We will also vaccinate with a mix of the 4 peptides and Montanide all injected at one site, as this will reduce the number of injections and could facilitate immunological helper effects of each peptide on the others. Finally, depending on the immunological results obtained with these two additional cohorts of patients, the best modality will be used in a larger study to evaluate clinical efficacy. No significant financial relationships to disclose.
American Cancer Society (ACS) clinical trial matching service (CTMS)
Authors: Gansler T. , Sharpe K. , Demler C. , Eyre H. 
Published: April 2020

18501 Background: The low prevalence of clinical trial participation limits progress in clinical research and practice. ACS assists individuals in finding trials appropriate to their medical and personal situation. Methods: The ACS call center and website provide access to a comprehensive cancer clinical trial database and matching software platform licensed from EmergingMed. This report outlines characteristics and outcomes of constituents who met initial eligibility criteria and requested further information for at least one trial after entering data on their diagnosis and prior treatment. Results: Among 4525 CTMS constituents during 2004–5, 58% were patients, 40% were their relatives and 2% were friends. 62% entered data via the call center, the rest used www.cancer.org (although for quality assurance reasons, all must speak with a call center specialist before receiving trial site contact information). They requested protocols for a median of 6 trials (range 1 to 75); most often requesting information on trials for lung cancer (16.4%), breast cancer (11.4%), colorectal cancer (7.3%), prostate cancer (7.0%), and melanoma (5.2%). Likelihood of trial enrollment varied by cancer type (χ2, p < 0.0001) and was highest with kidney cancer (10.7%), melanoma (7.8%), multiple myeloma (4.4%), head & neck cancer (4.4%), and leukemia (3.8%). We studied several common cancer types in greater detail. For example, in analysis of data from 2004, non-small cell lung cancer patients requesting trial information had more advanced disease than typical patients in the National Cancer Database (χ2, p < 0.001). Enrollment rates for patients with stage I-IIIA and IIIB-IV were 0% and 3.7% (NS), respectively; rates for those with ECOG performance 0–1 and >1 were 4.8% and 0.0% (χ2, p < 0.05). Conclusions: The ACS CTMS can substantially augment participation in clinical trials among patients not recruited into trials by their oncologists. No significant financial relationships to disclose.
Influence of the level of subjective distress of healthcare professionals on the perception of symptom intensity reported by patients with terminal cancer
Authors: Zloklikovits S. , Ladinek V. , Andritsch E. , Greimel A. , Pilgram E. H. , Strohscheer I. , Verebes J. , Springer-Schlegl I. , Stoger H. , Samonigg H. 
Published: April 2020

18503 Background: In palliative cancer care, effective symptom management requires knowledge of the factors influencing the accuracy of assessment by other raters. The aim of this study is to describe differences in symptom severity ratings between patients and their professional caregivers depending on the subjective level of distress of the proxy raters. Methods: A total of 50 patients with advanced cancer admitted to the palliative care unit of the University Hospital Graz, Austria participated in the study. Socio-demographic data, different physical, psychological and functional disorders as well as pain were assessed within the first three days after admission to the ward. Symptoms were rated independently by the patients themselves, their treating physicians as well as nurses using a modified standardized Symptom List for Quality Assurance in Palliative Care (MIDOS) drafted by the Working Group on the Core Documentation for Palliative Care Units in Germany and the psychological subscale of the Memorial Symptom Assessment Scale (MSAS-PSYCH). The Distress Thermometer (DT), a one item self-report measure, was completed by the different raters. Results: Statistical analyses were computed on individual symptoms (Mann-Whitney-U-Test) as well as different sum-scores for pain, physical/functional symptoms and psychological symptoms (ANOVAs). The preliminary results concerning the sum-scores showed that nurses significantly underestimated the intensity of patients’ pain (p = .005) and physical/functional symptoms (p = .022) whereas physicians agreed with the patients self-assessments. Both physicians and nurses scored psychological items (MSAS) more severe than the patients with significant higher scores for the physicians’ ratings (p = .015). In addition, comparisons between congruent and non-congruent rater dyads were analysed in relation to caregivers’ distress. Significant differences were found only for the pain sum-score, where nurses in the non-congruent dyads had significantly higher distress levels than nurses in the congruent dyads (p = .014). Conclusions: The findings indicate that at least the perception of pain of terminally-ill patients depends on healthcare professionals’ distress. No significant financial relationships to disclose.