bluuebunny/crossref_metadata_2025_split huggingface dataset:
The six-gene expression signature in whole sampled sputum provides clinically feasible inflammatory phenotyping of asthma
Authors: Frøssing Laurits , Kjærsgaard Klein Ditte , Backer Vibeke , Baines Katherine Joanne , Porsbjerg Celeste 
Published: March 2020

Processing of induced sputum is time consuming and requires trained personnel, and consequently the use of induced sputum is limited to few sites globally. The six-gene signature (6GS) is an mRNA-based gene signature that was developed to provide a clinically feasible method for inflammatory phenotyping. In this study, we assessed whether the 6GS would perform similarly in induced sputum sampled using a simplified method, by which induced sputum can be sampled and stored directly for later qPCR analyses, to the conventional method of manual plug selection.Two separate sputum samples were collected from 27 patients with asthma; one processed as a whole sample in an Oragene-RNA RE 100 vial and one processed using manual plug selection. Expression of 6GS was measured in both samples, of which 20 pairs (74%) had enough samples and results of sufficient quality of gene expression for further analyses.We found a significantly higher median RNA concentration in whole sampled sputum and consistently stronger gene expression compared to the plug method. Further, we found the two methods to agree, as 97% of observations were within the limits of agreement, as well as having a good-to-excellent reliability using intraclass correlation. Finally, we found 6GS in the whole sampled sputum to perform equal to or better than the manually selected plugs for discriminating inflammatory phenotypes defined by sputum differential count.In conclusion, whole sampling of induced sputum provides a clinically feasible method for inflammatory phenotyping.
Role of lateral amygdala calstabin2 in regulation of fear memory
Authors: Han Ren-wen , Liu Zhi-peng , Lin Hong-ru , Tian Ao-wen , Xiao Yun-fei , Wei Jie , Deng Ke-yu , Pan Bing-xing , Xin Hong-bo 
Published: March 2020

AbstractCalstabin2, also named FK506 binding protein 12.6 (FKBP12.6), is a subunit of ryanodine receptor subtype 2 (RyR2) macromolecular complex, an intracellular calcium channel. Studies from our and other’s lab have shown that hippocampal calstabin2 regulates spatial memory. Calstabin2 and RyR2 are widely distributed in the brain, including the amygdala, a key brain area involved in the regulation of emotion including fear. Little is known about the role of calstabin2 in fear memory. Here, we found that genetic deletion of calstabin2 impaired long-term memory in cued fear conditioning test. Knockdown calstabin2 in the lateral amygdala (LA) by viral vector also impaired long-term cued fear memory expression. Furthermore, calstabin2 knockout reduced long-term potentiation (LTP) at both cortical and thalamic inputs to the LA. In conclusion, our present data indicate that calstabin2 in the LA plays a crucial role in the regulating of emotional memory.
Alteration in the time and/or mode of delivery differentially modulates early development in mice
Authors: Chiesa Morgane , Ferrari Diana C. , Ben-Ari Yehezkel 
Published: March 2020

AbstractDelivery is a complex biological process involving hormonal and mechanical stimuli that together condition the survival and development of the fetus out of the womb. Accordingly, changes in the time or way of being born are associated with an alteration of fundamental biological functions and hypothesized to promote the emergence of neurodevelopmental disorders. Hence, the steadily rise in preterm birth and cesarean section (CS) delivery rates over the past years has become a worldwide health concern. In our previous work, we reported that even though no long-term autistic-like deficits were observed, mice born preterm by CS presented early transient neuronal and communicative defects. However, understanding if these alterations were due to an early birth combined with CS delivery, or if prematurity solely could lead to a similar outcome remained to be evaluated. Using mice born either at term or preterm by vaginal or CS delivery, we assessed early life ultrasonic vocalizations and the onset of eye opening. We report that alterations in communicative behaviors are finely attuned and specifically affected either by preterm birth or by the association between CS delivery and preterm birth in mice, while delayed onset of eye opening is due to prematurity. Moreover, our work further underlies a gender-dependent vulnerability to changes in the time and/or way of being born with distinct outcomes observed in males and females. Thus, our results shed light on the intricacy of birth alterations and might further explain the disparities reported in epidemiological studies.
The efficacy of Narrative Exposure Therapy for Children (KIDNET) as a treatment for traumatized young refugees versus treatment as usual: study protocol for a multi-center randomized controlled trial (YOURTREAT)
Authors: Wilker Sarah , Catani Claudia , Wittmann Jasmin , Preusse Melissa , Schmidt Telja , May Theodor , Ertl Verena , Doering Bettina , Rosner Rita , Zindler Areej , Neuner Frank 
Published: March 2020

Abstract
Background
Germany hosts a large number of refugees from war-affected countries. The integration of refugees, in particular young refugees from the Middle East, is one of the major current social challenges in Germany. Mental disorders, first of all post-traumatic stress disorder (PTSD) that results from war experiences, are common among young refugees and interfere with quality of life as well as functional integration. Evidence regarding effective treatment options for this population is scarce. In this trial, we aim to evaluate the pragmatic, short-term psychotherapy Narrative Exposure Therapy for Children (KIDNET) for the treatment of young refugees in Germany.

Methods
In a rater-blinded, multi-center, randomized-controlled trial, KIDNET is compared to treatment as usual (TAU) within the general health care system. A total number of 80 young refugees who fulfill the diagnostic criteria of PTSD will be randomized to either KIDNET or TAU. Diagnostic interviews will take place at baseline before treatment as well as 6 and 12 months thereafter. They will assess exposure to traumatic events, PTSD and comorbid symptoms, as well as parameters of integration.

Discussion
The results of this study should provide evidence regarding effective treatment options for young refugees in Germany, a population that has been understudied and received only limited access to mental health care so far. Next to the effects of treatment on mental health outcomes, integration parameters will be investigated. Therefore, this study should provide broad insights into treatment options for young refugees and their potential implications on successful integration.

Trial registration
German Clinical Trials Register (Deutsches Register Klinischer Studien; DRKS), ID: DRKS00017222. Registered on 15 May 2019.
Functional neuroimaging in subjective cognitive decline: current status and a research path forward
Authors: Viviano Raymond P. , Damoiseaux Jessica S. 
Published: March 2020

AbstractSubjective cognitive decline is a putative precursor to dementia marked by perceived worsening of cognitive function without overt performance issues on neuropsychological assessment. Although healthy older adults with subjective cognitive decline may function normally, perceived worsening may indicate incipient dementia and predict future deterioration. Therefore, the experience of decline represents a possible entry point for clinical intervention. However, intervention requires a physical manifestation of neuroabnormality to both corroborate incipient dementia and to target clinically. While some individuals with subjective cognitive decline may harbor pathophysiology for specific neurodegenerative disorders, many do not display clear indicators. Thus, disorder-agnostic brain measures could be useful to track the trajectory of decline, and functional neuroimaging in particular may be sensitive to detect incipient dementia and have the ability to track disease-related change when the underlying disease etiology remains unclear. Therefore, in this review, we discuss functional neuroimaging studies of subjective cognitive decline and possible reconciliations to inconsistent findings. We conclude by proposing a functional model where noisy signal propagation and inefficient signal processing across whole-brain networks may lead to the subjective experience of decline and discuss future research directions guided by this model.
Probiotic potential of lyophilized Lactobacillus plantarum GP
Authors: Shekh Satyamitra L. , Boricha Aarti A. , Chavda Jony G. , Vyas Bharatkumar Rajiv Manuel 
Published: March 2020

Abstract
Purpose
Freeze drying of Lactobacillus plantarum GP in the presence of wall materials to achieve improved survival and retention of probiotic functionality during storage.

Methods
L. plantarum cells were lyophilized in the presence of inulin, fructooligosaccharides, lactulose, and/or skim milk. The lyophilized vials were stored at 8–10 °C up to 6 months and cells from these vials were evaluated for their probiotic functionality.

Results
L. plantarum GP freeze dried in the presence of wall material lactulose displayed viability of 98 ± 2.8% promising survival rate in the stress conditions of human digestive tract. The freeze dried cells of Lactobacilli retained the ability to adhere intestinal mucin layer, form biofilm, inhibit food spoilage and enteropathogens, produce β-galactosidase, bile salt hydrolase and γ-amino butyric acid, remove cholesterol, and scavenge DPPH radical.

Conclusion
Lyophilized cells of L. plantarum GP retained all the functional characteristics without any significant loss during storage, which prompts to incorporate prebiotics for the development of stable functional food products.
Prevention of multiple system atrophy using human bone marrow-derived mesenchymal stem cells by reducing polyamine and cholesterol-induced neural damages
Authors: Park Kyung-Ran , Hwang Chul Ju , Yun Hyung-Mun , Yeo In Jun , Choi Dong-Young , Park Pil-Hoon , Kim Hyung Sook , Lee Jung Tae , Jung Young Suk , Han Sang-Bae , Hong Jin Tae 
Published: March 2020

AbstractBackgroundMultiple system atrophy (MSA) is a sporadic neurodegenerative disorder of unknown etiology, but is closely associated with damage to dopaminergic neurons. MSA progression is rapid. Hence, long-term drug treatments do not have any therapeutic benefits. We assessed the inhibitory effect of mesenchymal stem cells (MSCs) on double-toxin-induced dopaminergic neurodegenerative MSA.ResultsBehavioral disorder was significantly improved and neurodegeneration was prevented following MSC transplantation. Proteomics revealed lower expression of polyamine modulating factor-binding protein 1 (PMFBP1) and higher expression of 3-hydroxymethyl-3-methylglutaryl-CoA lyase (HMGCL), but these changes were reversed after MSC transplantation. In the in vitro study, the 6-OHDA-induced effects were reversed following co-culture with MSC. However, PMFBP1 knockdown inhibited the recovery effect due to the MSCs. Furthermore, HMGCL expression was decreased following co-culture with MSCs, but treatment with recombinant HMGCL protein inhibited the recovery effects due to MSCs.ConclusionsThese data indicate that MSCs protected against neuronal loss in MSA by reducing polyamine- and cholesterol-induced neural damage.
Molecular profiling of an osseous metastasis in glioblastoma during checkpoint inhibition: potential mechanisms of immune escape
Authors: Mohme Malte , Maire Cecile L. , Schliffke Simon , Joosse Simon A. , Alawi Malik , Matschke Jakob , Schüller Ulrich , Dierlamm Judith , Martens Tobias , Pantel Klaus , Riethdorf Sabine , Lamszus Katrin , Westphal Manfred 
Published: March 2020

AbstractPeripheral metastases of glioblastoma (GBM) are very rare despite the ability of GBM cells to pass through the blood-brain barrier and be disseminated through the peripheral blood. Here, we describe a detailed genetic and immunological characterization of a GBM metastasis in the skeleton, which occurred during anti-PD-1 immune checkpoint therapy. We performed whole genome sequencing (WGS) and 850 K methylation profiling of the primary and recurrent intracranial GBM as well as one of the bone metastases. Copy number alterations (CNA) and mutational profiles were compared to known genomic alterations in the TCGA data base. In addition, immunophenotyping of the peripheral blood was performed. The patient who was primarily diagnosed with IDH-wildtype GBM. After the resection of the first recurrence, progressive intracranial re-growth was again detected, and chemotherapy was replaced by PD-1 checkpoint inhibition, which led to a complete intracranial remission. Two months later MR-imaging revealed multiple osseous lesions. Biopsy confirmed the GBM origin of the skeleton metastases. Immunophenotyping reflected the effective activation of a peripheral T-cell response, with, however, increase of regulatory T cells during disease progression. WGS sequencing demonstrated distinct genomic alterations of the GBM metastasis, with gains along chromosomes 3 and 9 and losses along chromosome 4, 10, and 11. Mutational analysis showed mutations in potentially immunologically relevant regions. Additionally, we correlated tumour-infiltrating lymphocyte and microglia presence to the occurrence of circulating tumour cells (CTCs) in a larger cohort and found a decreased infiltration of cytotoxic T cells in patients positive for CTCs. This study exemplifies that the tumour microenvironment may dictate the response to immune checkpoint therapy. In addition, our study highlights the fact that despite an effective control of intracranial GBM, certain tumour clones have the ability to evade the tumour-specific T-cell response and cause progression even outside of the CNS.
Rubrics to assess critical thinking and information processing in undergraduate STEM courses
Authors: Reynders Gil , Lantz Juliette , Ruder Suzanne M. , Stanford Courtney L. , Cole Renée S. 
Published: March 2020

Abstract
Background
Process skills such as critical thinking and information processing are commonly stated outcomes for STEM undergraduate degree programs, but instructors often do not explicitly assess these skills in their courses. Students are more likely to develop these crucial skills if there is constructive alignment between an instructor’s intended learning outcomes, the tasks that the instructor and students perform, and the assessment tools that the instructor uses. Rubrics for each process skill can enhance this alignment by creating a shared understanding of process skills between instructors and students. Rubrics can also enable instructors to reflect on their teaching practices with regard to developing their students’ process skills and facilitating feedback to students to identify areas for improvement.

Results
Here, we provide rubrics that can be used to assess critical thinking and information processing in STEM undergraduate classrooms and to provide students with formative feedback. As part of the Enhancing Learning by Improving Process Skills in STEM (ELIPSS) Project, rubrics were developed to assess these two skills in STEM undergraduate students’ written work. The rubrics were implemented in multiple STEM disciplines, class sizes, course levels, and institution types to ensure they were practical for everyday classroom use. Instructors reported via surveys that the rubrics supported assessment of students’ written work in multiple STEM learning environments. Graduate teaching assistants also indicated that they could effectively use the rubrics to assess student work and that the rubrics clarified the instructor’s expectations for how they should assess students. Students reported that they understood the content of the rubrics and could use the feedback provided by the rubric to change their future performance.

Conclusion
The ELIPSS rubrics allowed instructors to explicitly assess the critical thinking and information processing skills that they wanted their students to develop in their courses. The instructors were able to clarify their expectations for both their teaching assistants and students and provide consistent feedback to students about their performance. Supporting the adoption of active-learning pedagogies should also include changes to assessment strategies to measure the skills that are developed as students engage in more meaningful learning experiences. Tools such as the ELIPSS rubrics provide a resource for instructors to better align assessments with intended learning outcomes.
A prospective study integrating a curriculum of interventional radiology in undergraduate education: a tetra-core simulation model
Authors: Theodoulou Iakovos , Louca Christina , Sideris Michail , Nicolaides Marios , Agrawal Deepsha , Halapas Antonios , Diamantopoulos Athanasios , Papalois Apostolos 
Published: March 2020

Abstract
Background
Interventional radiology (IR) is underrepresented in undergraduate medical curricula across Europe. By continuing to challenge the boundaries of IR, a rise in the demand for radiologists has been inevitable – a trend not met by a corresponding rise in the supply of radiologists. On tracing the roots of this shortage, lack of awareness of the specialty within medical trainees coupled with a global lack of IR teaching in undergraduate education seem to constitute major exacerbating factors. The purpose of this study was to identify gaps in the field of IR education and address these by implementing an international IR simulation-based course for undergraduates.

Results
Implementation of a multi-modality simulation-based course consisted of seven modules incorporating technical and non-technical skills, basic science and applied clinical science modules. Of all participants, 90.7% (N = 68) never had previous IR teaching experience and only 28% (N = 21) had a previous placement in an IR department. Following the course, confidence improvement was statistically significant both in IR skills (1/5, p < 0.01) and knowledge (1/5, p < 0.01)]. The majority (90.7%) said they would benefit with more exposure to IR. In terms of the students’ motivation for a career in IR, 32% (N = 24) reported that they would more likely consider a career in IR after completing the course.

Conclusion
Delivery of a tetra-core simulation course with the aim to address the gaps in undergraduate IR education has had a positive impact on students’ skills, confidence levels as well as motivation. We propose reviewing the curricula across medical schools in Europe to identify gaps and address any inadequacies; for this, we consider our simulation course an excellent starting point.
Superiority of melphalan-prednisone (MP) + thalidomide (THAL) over MP and autologous stem cell transplantation in the treatment of newly diagnosed elderly patients with multiple myeloma
Authors: Facon T. , Mary J. , Harousseau J. , Huguet F. , Berthou C. , Grosbois B. , Anglaret B. , Azzedine A. , Rodon P. , Peny A. 
Published: March 2020

1 Background: The standard MP regimen remains the reference treatment for elderly patients (pts) with multiple myeloma (MM). In May 2000, we initiated the IFM 99–06 trial, for pts aged 65–75 y, comparing MP (12 courses at 6 weeks intervals) to MP-THAL (MP plus THAL at the maximum tolerated dose, but ≤ 400 mg/day) and a MEL100-based treatment (VAD×2, CTX 3g/m2, and 2 courses of MEL100 mg/m2). Methods: IFM99–06 was planned to enroll 476 evaluable pts, whose treatment allocation followed a 3 (MP), 2 (MP-THAL), 2 (MEL100) randomization scheme. The primary end-point was overall survival (OS). Secondary end-points were response to treatment and progression-free survival (PFS). Two interim analyses were planned and reviewed by a Data Safety Monitoring Board (DSMB) independent of IFM. At the second interim analysis, the DSMB suggested that a third interim analysis be performed with a date of point on May 1, 2005. Results: At this time, 436 pts had been enrolled, 191, 124 and 121 in MP, MP-THAL and MEL100 groups, respectively. The median (se) follow-up time was 32.2 (1.8) months (mo.). Median (se) PFS times were 17.2 (1.5), 29.5 (3.6) and 19.0 (1.3) mo. in MP, MP-THAL and MEL100 groups, respectively. The PFS time was significantly longer in the MP-THAL group than in the MP group (RR=2.4, P<0.0001), but no significant difference was noted between MP and MEL100 groups (RR=1.2, P=0.12). There was a clear advantage in favor of MP-THAL vs MEL 100 (RR=2.0, P=0.0001). The PFS advantage in favor of MP-THAL translated to a significant benefit in terms of OS. Median (se) OS times were 30.3 (5.8) mo. (86 deaths), not reached at 56 mo.(34 deaths) and 38.6 (3.0) mo. (54 deaths) in MP, MP-THAL and MEL100 groups, respectively. The OS time was significantly longer in MP-THAL group than in MP group (RR=1.9, P=0.0008), but not significantly different between MP and MEL100 groups (RR=1.1, P=0.55). MP-THAL was also superior to MEL100 (RR=1.7, P=0.014). Conclusion: Since these results show the superiority of MP-THAL, enrollment was stopped. The final analysis will be presented at the meeting. MP-THAL should be, at the present time, the reference treatment for newly diagnosed MM pts ineligible for high-dose therapy. No significant financial relationships to disclose.
Pharmacogenomic predictor of complete response to preoperative paclitaxel and 5-fluorouracil, doxorubicin, cyclophosphamide chemotherapy in breast cancer
Authors: Pusztai L. , Hess K. R. , Anderson K. , Valero V. , Ibrahim N. K. , Mejia J. A. , Vidaurre T. , Gomez H. L. , Hortobagyi G. N. , Symmans W. F. 
Published: March 2020

10000 Background: We developed a multi-gene predictor of pathologic complete response (pCR) to preoperative weekly paclitaxel and 5-fluorouracil, doxorubicin, cyclophosphamide (T/FAC) chemotherapy and assessed its predictive accuracy on independent cases. Methods: 133 patients with stage I-III breast cancer were included. Pretreatment gene expression profiling was performed with Affymetrix U133 A chips on fine needle aspiration specimens. We developed predictors of pCR from 82 cases and assessed accuracy on 51 independent cases. Results: Overall pCR rate was 26% in both cohorts. In the training set, 56 probes (49 genes) were identified as differentially expressed between pCR versus residual disease at a false discovery rate of 1%. We examined the performance of 780 distinct classifiers (set of genes + prediction algorithm) in full cross validation. Many predictors performed equally well. A nominally best 30-probe set DLDA classifier was selected for independent validation. It showed substantially higher sensitivity (92% vs 61%), negative predictive value (96% vs 86%) and better AUC (0.877 vs 0.811) than a predictor including clinical variables (age, ER, grade). The combination of genomic and clinical information yielded the best model, AUC=0.883, sensitivity 92%, specificity 71%, PPV 52%, NPV 96%. In 31 samples, RNA was hybridized in replicate with resulting predictions that were 97% concordant. Conclusion: A 30-probe set pharmacogenomic predictor alone or in combination with ER and grade predicts response to T/FAC chemotherapy with high sensitivity and negative predictive value. This test correctly identified all but one of the patients who achieved pCR (12/13) and all but one of those who had residual cancer (27/28). No significant financial relationships to disclose.