bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular profile of FLT3-mutated relapsed/refractory patients with AML in the phase 3 ADMIRAL study of gilteritinib
Authors: Smith Catherine C. , Levis Mark J. , Perl Alexander E. , Hill Jason E. , Rosales Matt , Bahceci Erkut 
Published: February 2022

Abstract
The phase 3 Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation (ADMIRAL) trial demonstrated the superiority of the FLT3 inhibitor, gilteritinib, to salvage chemotherapy (SC) in patients with FLT3-mutated relapsed or refractory (R/R) AML. Baseline comutations, FLT3-internal tandem duplication (ITD) allelic ratio and length, and treatment-emergent mutations were analyzed in patients in the ADMIRAL trial. Baseline comutations were grouped according to gene subgroups (DNA methylation/hydroxymethylation, transcription, chromatin–spliceosome, receptor tyrosine kinase-Ras signaling, TP53-aneuploidy, NPM1, DNMT3A, DNMT3A/NPM1, WT-1, and IDH1/IDH2). Across all but 1 gene subgroup (TP53-aneuploidy), higher pretransplant response rates and a trend toward longer overall survival were observed with gilteritinib vs SC. Patients with DNMT3A/NPM1 comutations who received gilteritinib had the most favorable outcomes of any molecular subgroup analyzed. Survival outcomes with gilteritinib were not adversely affected by FLT3-ITD allelic ratio, FLT3-ITD length, or multiple FLT3-ITD mutations. Among patients who relapsed on gilteritinib, Ras/mitogen-activated protein kinase (MAPK) pathway and FLT3 F691L gene mutations were the most common mutational events associated with treatment resistance. However, the occurrence of Ras/MAPK pathway gene mutations at baseline did not preclude a clinical benefit from gilteritinib. Acquisition of multiple Ras/MAPK pathway gene mutations at relapse suggests a high level of pathway reactivation is needed to overcome the gilteritinib treatment effect. These findings provide insight into the R/R AML molecular profile and the impact of FLT3 inhibitors on mutational evolution associated with treatment resistance and benefit of gilteritinib across a wide spectrum of molecular and genetic subgroups in FLT3-mutated R/R AML. This trial was registered at www.clinicaltrials.gov as #NCT02421939.
A prognostic model to predict survival after 6 months of ruxolitinib in patients with myelofibrosis
Authors: Maffioli Margherita , Mora Barbara , Ball Somedeb , Iurlo Alessandra , Elli Elena Maria , Finazzi Maria Chiara , Polverelli Nicola , Rumi Elisa , Caramella Marianna , Carraro Maria Cristina , D’Adda Mariella , Molteni Alfredo , Sissa Cinzia , Lunghi Francesca , Vismara Alessandro , Ubezio Marta , Guidetti Anna , Caberlon Sabrina , Anghilieri Michela , Komrokji Rami , Cattaneo Daniele , Della Porta Matteo Giovanni , Giorgino Toni , Bertù Lorenza , Brociner Marco , Kuykendall Andrew , Passamonti Francesco 
Published: February 2022

AbstractRuxolitinib (RUX) is extensively used in myelofibrosis (MF). Despite its early efficacy, most patients lose response over time and, after discontinuation, have a worse overall survival (OS). Currently, response criteria able to predict OS in RUX-treated patients are lacking, leading to uncertainty regarding the switch to second-line treatments. In this study, we investigated predictors of survival collected after 6 months of RUX in 209 MF patients participating in the real-world ambispective observational RUXOREL-MF study (NCT03959371). Multivariable analysis identified the following risk factors: (1) RUX dose &lt;20 mg twice daily at baseline, months 3 and 6 (hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.07-3.00; P = .03), (2) palpable spleen length reduction from baseline ≤30% at months 3 and 6 (HR, 2.26; 95% CI, 1.40-3.65; P = .0009), (3) red blood cell (RBC) transfusion need at months 3 and/or 6 (HR, 1.66; 95% CI, 0.95-2.88; P = .07), and (4) RBC transfusion need at all time points (ie, baseline and months 3 and 6; HR, 2.32; 95% CI, 1.19-4.54; P = .02). Hence, we developed a prognostic model, named Response to Ruxolitinib After 6 Months (RR6), dissecting 3 risk categories: low (median OS, not reached), intermediate (median OS, 61 months; 95% CI, 43-80), and high (median OS, 33 months; 95% CI, 21-50). The RR6 model was validated and confirmed in an external cohort comprised of 40 MF patients. In conclusion, the RR6 prognostic model allows for the early identification of RUX-treated MF patients with impaired survival who might benefit from a prompt treatment shift.
A data management infrastructure for the integration of imaging and omics data in life sciences
Authors: Kuhn Cuellar Luis , Friedrich Andreas , Gabernet Gisela , de la Garza Luis , Fillinger Sven , Seyboldt Adrian , Koch Tobias , zur Oven-Krockhaus Sven , Wanke Friederike , Richter Sandra , Thaiss Wolfgang M. , Horger Marius , Malek Nisar , Harter Klaus , Bitzer Michael , Nahnsen Sven 
Published: February 2022

Abstract
Background
As technical developments in omics and biomedical imaging increase the throughput of data generation in life sciences, the need for information systems capable of managing heterogeneous digital assets is increasing. In particular, systems supporting the findability, accessibility, interoperability, and reusability (FAIR) principles of scientific data management.

Results
We propose a Service Oriented Architecture approach for integrated management and analysis of multi-omics and biomedical imaging data. Our architecture introduces an image management system into a FAIR-supporting, web-based platform for omics data management. Interoperable metadata models and middleware components implement the required data management operations. The resulting architecture allows for FAIR management of omics and imaging data, facilitating metadata queries from software applications. The applicability of the proposed architecture is demonstrated using two technical proofs of concept and a use case, aimed at molecular plant biology and clinical liver cancer research, which integrate various imaging and omics modalities.

Conclusions
We describe a data management architecture for integrated, FAIR-supporting management of omics and biomedical imaging data, and exemplify its applicability for basic biology research and clinical studies. We anticipate that FAIR data management systems for multi-modal data repositories will play a pivotal role in data-driven research, including studies which leverage advanced machine learning methods, as the joint analysis of omics and imaging data, in conjunction with phenotypic metadata, becomes not only desirable but necessary to derive novel insights into biological processes.
Maternal microbiota-derived metabolic profile in fetal murine intestine, brain and placenta
Authors: Pessa-Morikawa Tiina , Husso Aleksi , Kärkkäinen Olli , Koistinen Ville , Hanhineva Kati , Iivanainen Antti , Niku Mikael 
Published: February 2022

Abstract
Background
The maternal microbiota affects the development of the offspring by microbial metabolites translocating to the fetus. To reveal the spectrum of these molecular mediators of the earliest host-microbe interactions, we compared placenta, fetal intestine and brain from germ-free (GF) and specific pathogen free (SPF) mouse dams by non-targeted metabolic profiling.

Results
One hundred one annotated metabolites and altogether 3680 molecular features were present in significantly different amounts in the placenta and/or fetal organs of GF and SPF mice. More than half of these were more abundant in the SPF organs, suggesting their microbial origin or a metabolic response of the host to the presence of microbes. The clearest separation was observed in the placenta, but most of the molecular features showed significantly different levels also in the fetal intestine and/or brain. Metabolites that were detected in lower amounts in the GF fetal organs included 5-aminovaleric acid betaine, trimethylamine N-oxide, catechol-O-sulphate, hippuric and pipecolic acid. Derivatives of the amino acid tryptophan, such as kynurenine, 3-indolepropionic acid and hydroxyindoleacetic acid, were also less abundant in the absence of microbiota. Ninety-nine molecular features were detected only in the SPF mice. We also observed several molecular features which were more abundant in the GF mice, possibly representing precursors of microbial metabolites or indicators of a metabolic response to the absence of microbiota.

Conclusions
The maternal microbiota has a profound impact on the fetal metabolome. Our observations suggest the existence of a multitude of yet unidentified microbially modified metabolites which pass through the placenta into the fetus and potentially influence fetal development.
Factors related to treatment adherence behaviors among old-age hemodialysis patients in Hamadan, Iran: the application of the extended theory of planned behavior during Covid-19 pandemic
Authors: Sheikh Vida , Barati Majid , Khazaei Salman , Jormand Hanieh 
Published: February 2022

AbstractPurposeThis study aimed to identify the factors related to treatment adherence behaviors among old-age hemodialysis patients in Hamadan based on the Extended Theory of Planned Behavior (ETPB) during the covid-19 pandemic.MethodsThis cross-sectional study was conducted from January to March 2021 in Hamadan, Iran. 191 hemodialysis patients were recruited who were referred to hemodialysis centers via the census method. Data were collected by a questionnaire containing items on socio-demographic information, End-Stage Renal Disease Adherence (ESRD-Adherence) Questionnaire, and ETPB constructs scale. Data analysis was performed using descriptive statistics and structural equation modeling.ResultsThe mean (SD) age of participants was 62.49 (10.66). Also, the mean (SD) hemodialysis vintage/Month of them was 36.56 (43.34). Moreover, Treatment Adherence Behaviors are associated with education level, sex, and marital status (p < 0.001). Besides, Perceive Behavior Control (β = 0.414, t-value = 3.810) associated with intention. Also, intention (β = 0.158, t-value = 1.976) was associated to adherence behaviors. No significant associations were observed between positive attitudes, subjective norms, a perceived threat with intention, and adherence behaviors. The model explained about 54% of the variance of adherence behaviors. Finally, the goodness of fit index of 0.78, indicating the model good fit.ConclusionThe present study demonstrates that some of the ETPB constructs such as perceived behavior control and intention are useful to improve adherence among the oldest hemodialysis patients. Also. This framework is revealed alongside the theory of planned behavior (TPB) applicable in the treatment adherence of old-age hemodialysis patients.
Secular trends in incidence and mortality of cervical cancer in India and its states, 1990-2019: data from the Global Burden of Disease 2019 Study
Authors: Singh Mayank , Jha Ravi Prakash , Shri Neha , Bhattacharyya Krittika , Patel Priyanka , Dhamnetiya Deepak 
Published: February 2022

Abstract
Background
Cervical cancer is the fourth most common cancer that occurs to women worldwide. This study aims to assess trends in incidence and mortality of cervical cancer in India and its states over past three decades for tracking the progress of strategies for the prevention and control of cervical cancer.

Methods
Data on cervical cancer incidence and mortality from 1990 to 2019 for India and its states were extracted from Global Burden of Disease study and were utilized for the analysis. Spatial and rank map has been used to see the changes in incidence and mortality of cervical cancer in different Indian states. Further, joinpoint regression analysis is applied to determine the magnitude of the time trends in the age standardized incidence and mortality rates of cervical cancer. We obtained the average annual percent change (AAPC) and corresponding 95% confidence intervals (CI) for each state.

Results
Overall, from 1990 to 2019 Jharkhand (Incidence: -50.22%; Mortality: -56.16%) recorded the highest percentage decrement in cervical cancer incidence and mortality followed by the Himachal Pradesh (Incidence: -48.34%; Mortality: -53.37%). Tamilnadu (1st rank), Jammu & Kashmir and Ladakh (32nd rank) maintained the same rank over the period of three decade for age standardized cervical cancer incidence and mortality. The regression model showed a significant declining trend in India between 1990 and 2019 for age standardized incidence rate (AAPC: −0.82; 95%CI: −1.39 to −0.25; p < 0.05) with highest decline in the period 1998-2005 (AAPC: −3.22; 95%CI: −3.83 to −2.59; p < 0.05). Similarly, a significant declining trend was observed in the age standardized mortality rate of India between 1990 and 2019(AAPC: −1.35; 95%CI: −1.96 to −0.75; p < 0.05) with highest decline in the period 1998-2005 (AAPC: −3.52; 95%CI: −4.17 to −2.86; p < 0.05).

Conclusion
Though the incidence and mortality of cervical cancer declined over past three decades but it is still a major public health problem in India. Information, education and communication activities for girls, boys, parents and community for the prevention and control of cervical cancer should be provided throughout the country.
Neonatal mortality in a public referral hospital in southern Haiti: a retrospective cohort study
Authors: Dev Alka , Casseus Michelucia , Baptiste Wilhermine Jean , LeWinter Emma , Joseph Patrice , Wright Peter 
Published: February 2022

AbstractBackgroundHaiti has the highest rate of neonatal mortality in the Latin America and Caribbean region. While the rate of facility births in Haiti has doubled over the past two decades, there have been no comparable reductions in maternal or neonatal mortality. Little data is available on the clinical characteristics of complications and morbidities among newborns requiring hospitalization after birth and their contribution to neonatal mortality. There is a need to better understand the status of newborn clinical care capacity in Haiti to prioritize training and resources.MethodsWe performed a retrospective observational cohort study of neonates admitted to a large public referral hospital in southern Haiti in the first 2 years of operation of a new neonatal unit that we established. All neonate cases hospitalized in the unit in these 2 years were reviewed and analyzed to identify their clinical characteristics and outcomes. Multivariable logistic regression was used to identify independent risk factors of hospital mortality. We present the outcomes for 1399 neonates admitted to the unit during August 2017 and August 2019.ResultsThe leading cause of death was prematurity, followed by hypoxia and infection. Inborn neonates had better rates of hospital survival than those born elsewhere; they were also more likely to be born via cesarean section and to be admitted immediately following birth. There were no differences between the proportion of premature or low-birth-weight babies born at the hospital or elsewhere. Mortality in the second year of the unit’s operation was 12%, almost half that of the first year (21%). Multivariable regression analysis showed that mortality was consistently higher among premature and very low birthweight babies.ConclusionsWith modest investments, we were able to halve the mortality on a neonatal unit in Haiti. Resources are needed to address prematurity as an important outcome since hospital mortality was significant in this group. To this end, investment in uninterrupted supplies of oxygen and antibiotics, as well as ensuring adequate newborn resuscitation, infection control, laboratory testing, and timely morbidity and mortality reviews would go a long way toward lowering hospital mortality in Haiti.
Rising through the pandemic: a scoping review of quality improvement in public health during the COVID-19 pandemic
Authors: Yin X. Cindy , Pang Michelle , Law Madelyn P. , Guerra Fiona , O’Sullivan Tracey , Laxer Rachel E. , Schwartz Brian , Khan Yasmin 
Published: February 2022

Abstract
Background
The COVID-19 pandemic generated a growing interest in and need for evidence-based tools to facilitate the implementation of emergency management strategies within public health practice. Quality improvement (QI) is a key framework and philosophy to guide organizational emergency response efforts; however, the nature and extent to which it has been used in public health settings during the COVID-19 pandemic remains unclear.

Methods
We conducted a scoping review of literature published January 2020 – February 2021 and focused on the topic of QI at public health agencies during the COVID-19 pandemic. The search was conducted using four bibliographic databases, in addition to a supplementary grey literature search through custom Google search engines and targeted website search methods. Of the 1,878 peer-reviewed articles assessed, 15 records met the inclusion criteria. An additional 11 relevant records were identified during the grey literature search, for a total of 26 records included in the scoping review.

Results
Records were organized into five topics: 1) collaborative problem solving and analysis with stakeholders; 2) supporting learning and capacity building in QI; 3) learning from past emergencies; 4) implementing QI methods during COVID-19; and 5) evaluating performance using frameworks/indicators.

Conclusions
The literature indicates that QI-oriented activities are occurring at the organizational and program levels to enhance COVID-19 response. To optimize the benefits that QI approaches and methodologies may offer, it is important for public health agencies to focus on both widespread integration of QI as part of an organization’s management philosophy and culture, as well as project level activities at all stages of the emergency management cycle.
Final-year medical students’ self-assessment of facets of competence for beginning residents
Authors: Bußenius Lisa , Harendza Sigrid , van den Bussche Hendrik , Selch Susan 
Published: February 2022

Abstract
Background
Final-year undergraduate medical students often do not feel well prepared for their start of residency training. Self-assessment of competences is important so that medical trainees can take responsibility for their learning. In this study, we investigated how final-year medical students self-assessed their competences as they neared their transition to postgraduate training. The aim was to identify areas for improvement in undergraduate training.

Methods
In the academic year 2019/2020, a national online survey was sent to final-year undergraduate medical students via their respective medical schools. The survey included ten facets of competence (FOC) most relevant for beginning residents. The participants were asked to self-assess their competence for each FOC on a 5-point Likert scale (1: strongly disagree to 5: strongly agree). We established an order of self-assessed FOC performance by means and calculated paired t-tests. Gender differences were assessed with independent t-tests.

Results
A total of 1083 students from 35 medical schools completed the questionnaire. Mean age was 27.2 ± 3.1 years and 65.8% were female. Students rated their performance highest in the FOCs ‘Teamwork and collegiality’ and ‘Empathy and openness’ (97.1 and 95.0% ‘strongly agree’ or ‘agree’, respectively) and lowest in ‘Verbal communication with colleagues and supervisors’ and ‘Scientifically and empirically grounded method of working’ (22.8 and 40.2% ‘strongly disagree’, ‘disagree’, or ‘neither agree nor disagree’, respectively). Women rated their performance of ‘Teamwork and collegiality’, ‘Empathy and openness’, and ‘Knowing and maintaining own personal bounds and possibilities’ significantly higher than men did (Cohen’s d > .2), while men showed higher self-assessed performance in ‘Scientifically and empirically grounded method of working’ than women (Cohen’s d = .38). The FOCs ‘Responsibility’, ‘Knowing and maintaining own personal bounds and possibilities’, ‘Structure, work planning, and priorities’, ‘Coping with mistakes’, and ‘Scientifically and empirically grounded method of working’ revealed lower self-assessed performance than the order of FOC relevance established by physicians for beginning residents.

Conclusions
The differences between the level of students’ self-assessed FOC performance and physicians’ ranking of FOC relevance revealed areas for improvement in undergraduate medical education related to health system sciences. Final-year students might benefit from additional or better training in management skills, professionalism, and evidence-based medicine. Surveys of self-assessed competences may be useful to monitor competence development during undergraduate training.
Teaching critical appraisal to large classes of undergraduate medical students using team-based learning versus group discussions: a randomized controlled trial
Authors: Daou Dayane , Chakhtoura Marlene , El-Yazbi Ahmed , Mukherji Deborah , Sbaity Eman , Refaat Marwan M. , Nabulsi Mona 
Published: February 2022

AbstractBackgroundEvidence on the effectiveness of team-based learning in teaching critical appraisal to large classes of preclinical medical students is scarce. This study investigated whether team-based learning is effective in teaching critical appraisal to large classes of preclinical medical students.MethodsBetween April 2018 and May 2019, 107 first-year medical students were randomly allocated to receive instruction in critical appraisal using team-based learning or traditional group discussions as teaching methods. The primary outcome was students’ performance on the Berlin Questionnaire administered at the end of second year.ResultsStudents’ mean (SD) age was 22.0 (0.7) years. Baseline characteristics of the two groups were similar (allpvalues > 0.05). The mean (SD) Berlin scores of both groups were 80.4 (11.6) and 80.1 (12.1) for team-based learning and group discussions, respectively. Multivariate stepwise linear regression analysis revealed that the student’s academic achievement in medical school was the sole predictor of performance on the Berlin Questionnaire (ß= 1.079,p< 0.001), adjusting for gender, Medical College Admission Test score, student’s self-reported preferred teaching method, rank upon admission to medical school, score on the Epidemiology and Biostatistics course, and teaching method (team-based learning versus group discussions).ConclusionsTeam-based learning and group discussions were equally effective instructional strategies to teach critical appraisal to large classes of undergraduate medical students. Replication of our findings is needed in other educational settings.Trial RegistrationCurrent Controlled TrialsISRCTN15430424, retrospectively registered on December 30, 2021.