bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Choice Architecture on Sepsis Fluid Resuscitation Decisions: An Exploratory Survey-Based Study
Authors: Mansoori Jason N. , Clark Brendan J. , Havranek Edward P. , Douglas Ivor S. 
Published: May 2022

Background Discordance with well-known sepsis resuscitation guidelines is often attributed to rational assessments of patients at the point of care. Conversely, we sought to explore the impact of choice architecture (i.e., the environment, manner, and behavioral psychology within which options are presented and decisions are made) on decisions to prescribe guideline-discordant fluid volumes. Design We conducted an electronic, survey-based study using a septic shock clinical vignette. Physicians from multiple specialties and training levels at an academic tertiary-care hospital and academic safety-net hospital were randomized to distinct answer sets: control (6 fluid options), time constraint (6 fluid options with a 10-s limit to answer), or choice overload (25 fluid options). The primary outcome was discordance with Surviving Sepsis Campaign fluid resuscitation guidelines. We also measured response times and examined the relationship between each choice architecture intervention group, response time, and guideline discordance. Results A total of 189 of 624 (30.3%) physicians completed the survey. Time spent answering the vignette was reduced in time constraint (9.5 s, interquartile range [IQR] 7.3 s to 10.0 s, P < 0.001) and increased in choice overload (56.8 s, IQR 35.9 s to 86.7 s, P < 0.001) groups compared with control (28.3 s, IQR 20.0 s to 44.6 s). In contrast, the relative risk of guideline discordance was higher in time constraint (2.07, 1.33 to 3.23, P = 0.001) and lower in choice overload (0.75, 0.60, to 0.95, P =0.02) groups. After controlling for time spent reading the vignette, the overall odds of choosing guideline-discordant fluid volumes were reduced for every additional second spent answering the vignette (OR 0.98, 0.97, to 0.99, P < 0.001). Conclusions Choice architecture may affect fluid resuscitation decisions in sepsis regardless of patient conditions, warranting further investigation in real-world contexts. These effects should be considered when implementing practice guidelines. Highlights Time constrained clinical decision making was associated with increased proportion of guideline-discordant responses and relative risk of failure to prescribe guideline-recommended intravenous fluids using a sepsis clinical vignette. Choice overload increased response times and was associated with decreased proportion of guideline-discordant responses and relative risk of guideline discordance. Physician odds of choosing to prescribe guideline-discordant fluid volumes were reduced with increased deliberation as measured by response times. Clinicians, researchers, policy makers, and administrators should consider the effect of choice architecture on clinical decision making and guideline discordance when implementing guidelines for sepsis and other acute care conditions.
Implementing Kolb´s Experiential Learning Cycle by Linking Real Experience, Case-Based Discussion and Simulation
Authors: Wijnen-Meijer M. , Brandhuber T. , Schneider A. , Berberat P.O. 
Published: May 2022

BACKGROUND Background: To prepare medical students for their future, they must become acquainted with clinical practice, for example by means of simulations, clerkships and discussing patient cases. By connecting these different approaches, according to Kolb´s experiential learning cycle, the learning effect can be strengthened. Methodology In the development of a didactical program for students who are being prepared for their role as general practitioners, we have adopted a new didactic approach, in which educational formats are interlinked, according to Kolb´s experiential learning cycle. The content of these courses is determined by the Entrustable Professional Activities (EPAs) for the clerkship in family medicine, combined with the most common chief complaints of patients in the GP's practice. In 2019, the first course was implemented at the Technical University of Munich, Germany, with 6 medical students. A first seminar discusses patients who the students have seen for themselves during their clerkship in family medicine. In addition, matching theory is discussed and skills are practiced. In the next seminar, students apply the acquired knowledge and skills in scenarios with standardized patients. Students evaluated the courses as positive. The evaluations show they find discussing personally experienced patient cases and the opportunity to practice very valuable. Conclusions A course design according to Kolb's Experiential learning cycle, which integrates experience, theory and simulation, is a valuable addition to existing forms of teaching in medical education. Students appreciated both discussing personally experienced patient cases and the opportunity to re-practice similar cases in a simulated environment. To gain more insight into the learning effects, it is recommended to further explore this approach in a different context.
Reflective Essays During Clerkship Following a Pre-clerkship Leadership Curriculum
Authors: Wiseman Melanie , Hartzell Joshua , Kelly William F. , Hemmer Paul A. , Stein Michael 
Published: May 2022

Introduction Leadership curricula in medical student education require assessment - to determine if leadership skills can be taught to medical students and applied during clinical and medical team interactions to aid in medical student leadership development. Objectives To examine whether medical students applied principles of their pre-clerkship leadership curriculum (character, competence, context, and communication elements across four levels: personal, interpersonal, team, and organizational) during an internal medicine clerkship. Methods Using art as a prompt, Uniformed Services University (USU) internal medicine clerkship students completed a structured reflection on a critical incident. Medical student essays written during a 10-week internal medicine clerkship at USU in 2019 were collected. 158 medical student submissions were de-identified and analyzed. Results Sixty-four submissions (40.5%) focused on leadership or leadership and professionalism. Students identified as male (n = 34, 53%), female (21, 33%), or not reported (9, 14%). Most, 48 (75%), did not describe PITO explicitly in their essay. They instead focused on personal and interpersonal aspects (17, 27%) of leadership, the attending physicians they worked with (33, 52%), and effective leadership strategies (46, 72%). The most common themes written about were responsibility (30, 47%), teamwork (18, 28%), competence (17, 27%), and character/integrity (15, 23%). Conclusion Although the students’ explicit use of the PITO model was limited, student essays centered on themes that reflected leadership concepts taught in pre-clerkship years, such as character, competence, and responsibility. This study demonstrates that an internal medicine clerkship rotation can feasibly implement a leadership reflection.
Posterior Polar Hemispheric Choroidal Dystrophy: Case Report and Presentation of Genetic Screening
Authors: Tabbaa Tarek , Daroszewski Daniel , Sobol Warren 
Published: May 2022

Purpose: Posterior polar hemispheric choroidal dystrophy is a rare dystrophy affecting the choroid and retina with a characteristic clinical appearance that distinguishes it from a broad variety of other retinal diseases. The disease process has a morphology described in the literature that preferentially affects the outer macula and spares the fovea with no arteriolar attenuation or optic nerve pallor. Methods: This case report illustrates the use of multimodal retinal imaging, visual field testing, electroretinogram, and genetic testing of a patient who we believe fits the clinical pattern established by previous studies describing this condition. Results: Fundus imaging in addition to further imaging modalities such as fluorescein angiography helped further characterize this disease process and aided in the diagnosis. In addition, genetic testing revealed unique allele variants found in this patient. Conclusions: By taking a multifaceted approach to the diagnosis of retinal pathology, clinicians can make informed decisions regarding patient care.
Retinoblastoma in the Presence of Persistent Fetal Vasculature
Authors: El Hamichi Sophia , Feria Anzaldo Estephania , Gold Aaron S. , Dubovy Sander R. , Murray Timothy G. 
Published: May 2022

Purpose: This work aims to report the challenging diagnosis, treatment, and follow-up of a patient with persistent fetal vasculature (PFV) and retinoblastoma (RB). Methods: A 22-month-old boy presented with unilateral RB stage VB in the right eye and PFV in both eyes. The patient was treated with transpupillary laser ablation and systemic chemotherapy. Results: Treatment resulted in complete tumor regression. Two years after the last systemic chemotherapy treatment, magnetic resonance imaging (MRI) showed increased signal intensity with progressive optic nerve enhancement, where intraneural malignancy could not be excluded. Enucleation of the right eye was performed. Histopathologic review showed no residual active malignancy in the enucleated globe. Conclusions: This case demonstrates the importance of a thorough clinical examination to establish the correct diagnosis and to rule out RB before any surgery. This case also highlights the importance of regular follow-ups after tumor regression with full a ophthalmologic examination, B-scan, and periodic MRI.
Coverage of Specialty Drugs for Psoriasis and Psoriatic Arthritis by Commercial Insurance Companies
Authors: Learned Christine , Alsukait Sara , Fiumara Kristin R , Ortega Melissa , Chambers James D , Rosmarin David 
Published: May 2022

Background Specialty medications provide effective treatment with limited adverse effects to patients with psoriasis and psoriatic arthritis; however, variable coverage and high costs often create a barrier to treatment for patients with commercial health insurance. Objective We aimed to evaluate coverage of psoriasis and psoriatic arthritis specialty medications by commercial insurance companies. Methods We compiled data regarding specialty drug coverage for psoriasis and psoriatic arthritis using Tufts Medical Center Specialty Drug Evidence and Coverage (SPEC) database and analyzed the data for any notable trends. The SPEC database lists coverage decisions for 158 specialty drugs by 17 of the largest US commercial health plans, as well as data regarding the types of evidence cited by these insurance plans when making coverage decisions. Results Our results showed that insurance plans tend to be more restrictive than the U.S. Food and Drug Association (FDA) label when covering medications for psoriasis and psoriatic arthritis. Furthermore, medications for psoriatic arthritis tended to be less restricted than for psoriasis, and medications were most commonly approved as second line agents for both indications. Conclusion Our analysis confirms that variability in insurance coverage exists for the indications of psoriasis and psoriatic arthritis.
Open Shoulder Stabilization for Anterior Glenohumeral Instability: The Latarjet Procedure
Authors: Morris Jesse H. , Barrazueta Gustavo A. , Cvetanovich Gregory L. 
Published: May 2022

Background: Traumatic anterior glenohumeral instability is a commonly encountered shoulder pathology among young active patients. Nonoperative management and arthroscopic techniques are associated with high rates of reoccurrence, particularly in patient populations with known major risk factors. Indications: The coracoid process transfer (Latarjet procedure) is typically reserved for cases of anterior glenohumeral instability where glenoid deficiency exceeds 20% to 25% or when soft tissue stabilization techniques have failed. Technique Description: We use a standard open deltopectoral approach. The coracoid process is exposed and released from the pectoralis minor and coracoacromial ligament. An osteotomy is performed using an oscillating saw and completed with an osteotome to harvest the bone block, leaving the conjoint tendon intact. Soft tissue is cleared from the graft, and it is predrilled/measured. We use a subscapularis splitting technique to access the joint and expose the anterior glenoid. All bony surfaces are prepared. We drill into the glenoid at the premeasured offset. The graft is provisionally fixed into place with K wires, then secured with 2 parallel cannulated screws. The capsule is repaired to make the graft extraarticular. The subscapularis split is repaired in addition to standard closure. Results: The Latarjet procedure is very successful for restoring stability. Rates of recurrent dislocation range from 0% to 10% across various studies, and revision rates are as small as 3%. This is much lower than those seen following soft tissue stabilization, particularly in high-risk patient populations. Patient reported outcomes show good function and high rates of return to sport. Complication rates are generally higher, with some studies reporting up to 25% incidence. Musculocutaneous and axillary nerve injuries may occur, and graft overhang can lead to glenohumeral arthritis. Certain complications are unique to the procedure, including graft lysis, coracoid fracture, nonunion, and hardware issues. Discussion/Conclusion: The Latarjet procedure is very useful in cases of anterior glenohumeral instability with significant glenoid bone loss or following failed soft tissue stabilization. Its utilization may continue to grow in future years as technique innovations develop and surgical indications expand.
Fatal thrombotic microangiopathy case following adeno-associated viral SMN gene therapy
Authors: Guillou Julia , de Pellegars Alice , Porcheret Florence , Frémeaux-Bacchi Véronique , Allain-Launay Emma , Debord Camille , Denis Manon , Péréon Yann , Barnérias Christine , Desguerre Isabelle , Roussey Gwenaëlle , Mercier Sandra 
Published: May 2022

Abstract
Adeno-associated virus (AAV) gene therapies are highly promising, such as the onasemnogene abeparvovec (Zolgensma) in spinal muscle atrophy (SMA). We report the first case of fatal systemic thrombotic microangiopathy (TMA) following onasemnogene abeparvovec in a 6-month-old child with SMA type 1, carrying a potential genetic predisposition in the complement factor I gene. Other cases of TMA have recently been reported after onasemnogene abeparvovec and after AAV9 minidystrophin therapy in Duchenne muscular dystrophy. The risk-benefit ratio of this therapy must therefore be assessed. Early recognition of TMA and targeted immunotherapy are fundamental to ensure the safety of patients treated with AAV gene therapies.
Evaluation of statistical approaches for association testing in noisy drug screening data
Authors: Smirnov Petr , Smith Ian , Safikhani Zhaleh , Ba-alawi Wail , Khodakarami Farnoosh , Lin Eva , Yu Yihong , Martin Scott , Ortmann Janosch , Aittokallio Tero , Hafner Marc , Haibe-Kains Benjamin 
Published: May 2022

AbstractBackgroundIdentifying associations among biological variables is a major challenge in modern quantitative biological research, particularly given the systemic and statistical noise endemic to biological systems. Drug sensitivity data has proven to be a particularly challenging field for identifying associations to inform patient treatment.ResultsTo address this, we introduce two semi-parametric variations on the commonly used concordance index: the robust concordance index and the kernelized concordance index (rCI, kCI), which incorporate measurements about the noise distribution from the data. We demonstrate that common statistical tests applied to the concordance index and its variations fail to control for false positives, and introduce efficient implementations to compute p-values using adaptive permutation testing. We then evaluate the statistical power of these coefficients under simulation and compare with Pearson and Spearman correlation coefficients. Finally, we evaluate the various statistics in matching drugs across pharmacogenomic datasets.ConclusionsWe observe that the rCI and kCI are better powered than the concordance index in simulation and show some improvement on real data. Surprisingly, we observe that the Pearson correlation was the most robust to measurement noise among the different metrics.
PhyloMissForest: a random forest framework to construct phylogenetic trees with missing data
Authors: Pinheiro Diogo , Santander-Jimenéz Sergio , Ilic Aleksandar 
Published: May 2022

Abstract
Background
In the pursuit of a better understanding of biodiversity, evolutionary biologists rely on the study of phylogenetic relationships to illustrate the course of evolution. The relationships among natural organisms, depicted in the shape of phylogenetic trees, not only help to understand evolutionary history but also have a wide range of additional applications in science. One of the most challenging problems that arise when building phylogenetic trees is the presence of missing biological data. More specifically, the possibility of inferring wrong phylogenetic trees increases proportionally to the amount of missing values in the input data. Although there are methods proposed to deal with this issue, their applicability and accuracy is often restricted by different constraints.

Results
We propose a framework, called PhyloMissForest, to impute missing entries in phylogenetic distance matrices and infer accurate evolutionary relationships. PhyloMissForest is built upon a random forest structure that infers the missing entries of the input data, based on the known parts of it. PhyloMissForest contributes with a robust and configurable framework that incorporates multiple search strategies and machine learning, complemented by phylogenetic techniques, to provide a more accurate inference of lost phylogenetic distances. We evaluate our framework by examining three real-world datasets, two DNA-based sequence alignments and one containing amino acid data, and two additional instances with simulated DNA data. Moreover, we follow a design of experiments methodology to define the hyperparameter values of our algorithm, which is a concise method, preferable in comparison to the well-known exhaustive parameters search. By varying the percentages of missing data from 5% to 60%, we generally outperform the state-of-the-art alternative imputation techniques in the tests conducted on real DNA data. In addition, significant improvements in execution time are observed for the amino acid instance. The results observed on simulated data also denote the attainment of improved imputations when dealing with large percentages of missing data.

Conclusions
By merging multiple search strategies, machine learning, and phylogenetic techniques, PhyloMissForest provides a highly customizable and robust framework for phylogenetic missing data imputation, with significant topological accuracy and effective speedups over the state of the art.
Using unique ORFan genes as strain-specific identifiers for Escherichia coli
Authors: Ferrandis-Vila Marta , Tiwari Sumeet K. , Mamerow Svenja , Semmler Torsten ,   HECTOR consortium, Ferrandis-Vila Marta , Tiwari Sumeet K. , van der Putten Boas , Trung Nguyen V. , Oldenkamp Rik , Bootsma Martin , Matamoros Sebastien , Ngo Hoa T. , Alvarez Julio , Ritchie Jennifer M. , Fivian-Hughes Amanda , Fruth Angelika , Leng Joy , La Ragione Roberto M. , Ugarte-Ruiz Maria , Bethe Astrid , Schwarz Stefan , Semmler Torsten , Schultsz Constance , Menge Christian , Berens Christian , Menge Christian , Berens Christian 
Published: May 2022

Abstract
Background
Bacterial identification at the strain level is a much-needed, but arduous and challenging task. This study aimed to develop a method for identifying and differentiating individual strains among multiple strains of the same bacterial species. The set used for testing the method consisted of 17 Escherichia coli strains picked from a collection of strains isolated in Germany, Spain, the United Kingdom and Vietnam from humans, cattle, swine, wild boars, and chickens. We targeted unique or rare ORFan genes to address the problem of selective and specific strain identification. These ORFan genes, exclusive to each strain, served as templates for developing strain-specific primers.

Results
Most of the experimental strains (14 out of 17) possessed unique ORFan genes that were used to develop strain-specific primers. The remaining three strains were identified by combining a PCR for a rare gene with a selection step for isolating the experimental strains. Multiplex PCR allowed the successful identification of the strains both in vitro in spiked faecal material in addition to in vivo after experimental infections of pigs and recovery of bacteria from faecal material. In addition, primers for qPCR were also developed and quantitative readout from faecal samples after experimental infection was also possible.

Conclusions
The method described in this manuscript using strain-specific unique genes to identify single strains in a mixture of strains proved itself efficient and reliable in detecting and following individual strains both in vitro and in vivo, representing a fast and inexpensive alternative to more costly methods.
Genetic mapping and physiological analysis of chlorophyll-deficient mutant in Brassica napus L
Authors: Lin Na , Gao Yumin , Zhou Qingyuan , Ping Xiaoke , Li Jiana , Liu Liezhao , Yin Jiaming 
Published: May 2022

AbstractBackgroundLeaf color mutants have reduced photosynthetic efficiency, which has severely negative impacts on crop growth and economic product yield. There are different chlorophyll mutants inArabidopsisand crops that can be used for genetic control and molecular mechanism studies of chlorophyll biosynthesis, chloroplast development and photoefficiency. Chlorophyll mutants inBrassica napusare mostly used for mapping and location research but are rarely used for physiological research. The chlorophyll-deficient mutant in this experiment were both genetically mapped and physiologically analyzed.ResultsIn this study, yellow leaf mutant ofBrassica napusL. mutated by ethyl methyl sulfone (EMS) had significantly lower chlorophyll a, b and carotenoid contents than the wild type, and the net photosynthetic efficiency, stomatal conductance and transpiration rate were all significantly reduced. The mutant had sparse chloroplast distribution and weak autofluorescence. The granule stacks were reduced, and the shape was extremely irregular, with more broken stromal lamella. Transcriptome data analysis enriched the differentially expressed genes mainly in phenylpropane and sugar metabolism. The mutant was mapped to a 2.72 Mb region on A01 by using BSA-Seq, and the region was validated by SSR markers.ConclusionsThe mutant chlorophyll content and photosynthetic efficiency were significantly reduced compared with those of the wild type. Abnormal chloroplasts and thylakoids less connected to the stroma lamella appeared in the mutant. This work on the mutant will facilitate the process of cloning theBnaA01.cdgene and provide more genetic and physiological information concerning chloroplast development inBrassica napus.