bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can we do that here? An analysis of US federal and state policies guiding human embryo and embryoid research
Authors: Matthews Kirstin R W , Morali Daniel 
Published: April 2022

Abstract
Recent technological advances have helped scientists understand early human development. However, scientists’ ability to fully explore their potential comes in conflict with national and state-level policies in the USA. In 2016, for the first time, researchers were able to grow human embryos in culture up to 14 days but stopped because of scientific and legal limits. Other researchers have used stem cells in culture to create organized models of early human development, known as embryoids or cell-based embryo models. In this paper, we review federal and state laws that affect US human embryo and embryoid research. While federal policies focus on funding, state laws are often associated with human embryonic stem cells, abortion, fetal tissue research, and reproductive cloning. Of the 29 states with laws impacting human embryo research, only 11 states ban it, and none address embryoids directly, although five states limit aspects of this research. Overall, this complicated landscape suggests that additional national guidance would help scientists and the public navigate these controversial areas of research, however, it is unlikely to happen, considering the lack of past progress determining embryo research policy.
Obesity: an evolutionary context
Authors: Speakman John R , Elmquist Joel K 
Published: April 2022

AbstractPeople completely lacking body fat (lipodystrophy/lipoatrophy) and those with severe obesity both show profound metabolic and other health issues. Regulating levels of body fat somewhere between these limits would, therefore, appear to be adaptive. Two different models might be contemplated. More traditional is a set point (SP) where the levels are regulated around a fixed level. Alternatively, dual-intervention point (DIP) is a system that tolerates fairly wide variation but is activated when critically high or low levels are breached. The DIP system seems to fit our experience much better than an SP, and models suggest that it is more likely to have evolved. A DIP system may have evolved because of two contrasting selection pressures. At the lower end, we may have been selected to avoid low levels of fat as a buffer against starvation, to avoid disease-induced anorexia, and to support reproduction. At the upper end, we may have been selected to avoid excess storage because of the elevated risks of predation. This upper limit of control seems to have malfunctioned because some of us deposit large fat stores, with important negative health effects. Why has evolution not protected us against this problem? One possibility is that the protective system slowly fell apart due to random mutations after we dramatically reduced the risk of being predated during our evolutionary history. By chance, it fell apart more in some people than others, and these people are now unable to effectively manage their weight in the face of the modern food glut. To understand the evolutionary context of obesity, it is important to separate the adaptive reason for storing some fat (i.e. the lower intervention point), from the nonadaptive reason for storing lots of fat (a broken upper intervention point). The DIP model has several consequences, showing how we understand the obesity problem and what happens when we attempt to treat it.
What Determines Consumer Financial Distress? Place- and Person-Based Factors
Authors: Keys Benjamin J , Mahoney Neale , Yang Hanbin 
Published: April 2022

Abstract
We use credit report data to study consumer financial distress in America. We report large, persistent disparities in financial distress across regions. To understand these patterns, we conduct a “movers” analysis. For collections and default, there is only weak convergence following a move, suggesting these types of distress are not primarily caused by place-based factors (e.g., local economic conditions and state laws) but instead reflect person-based characteristics (e.g., financial literacy and risk preferences). In contrast, for personal bankruptcy, we find a sizable place-based effect, which is consistent with anecdotal evidence on how local legal factors influence personal bankruptcy.
Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Efficacy and Safety of MSC Cell Therapies for Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis
Authors: Qu Wenchun , Wang Zhen , Engelberg-Cook Erica , Yan Dan , Siddik Abu Bakar , Bu Guojun , Allickson Julie G , Kubrova Eva , Caplan Arnold I , Hare Joshua M , Ricordi Camillo , Pepine Carl J , Kurtzberg Joanne , Pascual Jorge M , Mallea Jorge M , Rodriguez Ricardo L , Nayfeh Tarek , Saadi Samer , Durvasula Ravindra V , Richards Elaine M , March Keith , Sanfilippo Fred P 
Published: April 2022

Abstract
MSC (a.k.a. mesenchymal stem cell or medicinal signaling cell) cell therapies show promise in decreasing mortality in acute respiratory distress syndrome (ARDS) and suggest benefits in treatment of COVID-19-related ARDS. We performed a meta-analysis of published trials assessing the efficacy and adverse events (AE) rates of MSC cell therapy in individuals hospitalized for COVID-19. Systematic searches were performed in multiple databases through November 3, 2021. Reports in all languages, including randomized clinical trials (RCTs), non-randomized interventional trials, and uncontrolled trials, were included. Random effects model was used to pool outcomes from RCTs and non-randomized interventional trials. Outcome measures included all-cause mortality, serious adverse events (SAEs), AEs, pulmonary function, laboratory, and imaging findings. A total of 736 patients were identified from 34 studies, which included 5 RCTs (n = 235), 7 non-randomized interventional trials (n = 370), and 22 uncontrolled comparative trials (n = 131). Patients aged on average 59.4 years and 32.2% were women. When compared with the control group, MSC cell therapy was associated with a reduction in all-cause mortality (RR = 0.54, 95% CI: 0.35-0.85, I  2 = 0.0%), reduction in SAEs (IRR = 0.36, 95% CI: 0.14-0.90, I  2 = 0.0%) and no significant difference in AE rate. A sub-group with pulmonary function studies suggested improvement in patients receiving MSC. These findings support the potential for MSC cell therapy to decrease all-cause mortality, reduce SAEs, and improve pulmonary function compared with conventional care. Large-scale double-blinded, well-powered RCTs should be conducted to further explore these results.
Clinical Correlates of Depression and Suicidality in Huntington Disease: An Analysis of the Enroll-HD Observational Study
Authors: Rocha Natalia P. , Tuazon Madison R. , Patino Jorge , Furr Stimming Erin , Teixeira Antonio L. 
Published: April 2022

Background:
Depression and suicidality are commonly experienced by Huntington disease (HD) gene carriers. Research on these behavioral symptoms is imperative, not only to increase our understanding of the symptoms and how they relate to HD, but also to contribute to improving patients’ care and quality of life.

Objective:
To identify clinical variables associated with a history of depression and suicidality in HD gene carriers.

Method:
We conducted a cross-sectional study of HD gene carriers from the Enroll-HD database PDS4 (periodic data set 4; N = 11,582). Data from baseline visits were obtained, and binary logistic regression models were used to ascertain the effects of clinical variables on the likelihood that HD gene carriers would have previous depression and suicidal ideation/attempts.

Results:
Approximately 65% (n = 7526) of the HD gene carriers had a history of depression, and ~27% (n = 3152) had previous suicidal ideation/attempts. Female sex; diagnosis of manifest HD; history of perseverative/obsessive behavior, apathy, and psychosis; and previous suicidal ideation/attempts were significantly associated with a history of depression in the HD gene carriers. Medical history of apathy, psychosis, and depression, as well as worse scores on the Total Functional Capacity and Irritability Scales, were significantly associated with previous suicidal ideation/attempts in the HD gene carriers.

Conclusion:
The prevalence of depression and suicidality is high among HD gene carriers. An improved understanding of the risk factors for depression and suicide in HD gene carriers can assist providers in recognizing at-risk individuals and allow providers to implement therapeutic strategies.
Delirium as a Presenting Symptom of COVID–19
Authors: Tyson Brad , Shahein Ayman , Erdodi Laszlo , Tyson Leigh , Tyson Robert , Ghomi Reza , Agarwal Pinky 
Published: April 2022

Background:
Delirium is a common neurologic manifestation of coronavirus disease 2019 (COVID–19) in older adults who present to the emergency department (ED).

Objective:
To investigate clinical characteristics associated with delirium as a presenting symptom of COVID–19 in older adults and develop a logistic regression to predict the likelihood of delirium.

Method:
We compared clinical characteristics in an age- and gender-matched sample of 68 delirious individuals with 68 nondelirious individuals (Mage = 78) who presented to the ED with COVID–19.

Results:
The delirious group was more likely to have neurologic, psychiatric, and cardiovascular comorbidities; a prior history of delirium; and deliriogenic medications in their medication list. They were less likely to present with respiratory symptoms and more likely to present with sepsis, hypoxia, higher heart rate, and higher sodium. The delirious group had higher mortality (51%) than the nondelirious group (32%). Delirium developed within an average of 2 days of initial COVID–19 symptom onset, with symptom onset to ED within an average of 4 days and symptom onset to death within an average of 11 days. Logistic regression based on five delirium predictors correctly predicted 80% of those with delirium (75% sensitivity at 86% specificity).

Conclusion:
Our results are largely consistent with prior studies and suggest that delirium is a common, early occurring, and lethal manifestation of COVID–19 in older adults presenting to the ED, in most cases causing acute on chronic neurocognitive dysfunction strongly influenced by inflammatory and hypoxic–ischemic mechanisms.
Real-time monitoring of endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation
Authors: Harish Rohit Krishnan , Gupta Mansi , Zöller Daniela , Hartmann Hella , Gheisari Ali , Machate Anja , Hans Stefan , Brand Michael 
Published: April 2022

AbstractMorphogen gradients impart positional information to cells in a homogenous tissue field. Fgf8a, a highly conserved growth factor, has been proposed to act as a morphogen during zebrafish gastrulation. However, technical limitations have so far prevented direct visualization of the endogenous Fgf8a gradient and confirmation of its morphogenic activity. Here, we monitored Fgf8a propagation in the developing neural plate using a CRISPR/Cas9-mediated EGFP knock-in at the endogenousfgf8alocus. By combining sensitive imaging platforms with single-molecule Fluorescence Correlation Spectroscopy (FCS), we demonstrate that Fgf8a, produced at the embryonic margin, propagates by free diffusion through the extracellular space and forms a graded distribution towards the animal pole. Overlaying the Fgf8a gradient curve with expression profiles of its downstream targets determines the precise input-output relationship of Fgf8a mediated patterning. Manipulation of the Fgf8a input alters the signaling outcome, thereby establishing Fgf8a as a bona fide morphogen during zebrafish gastrulation. Furthermore, using diffusion-hindered versions of Fgf8a, we demonstrate that extracellular diffusion of the protein from the source is critical for it to achieve its morphogenic potential.
Chemotherapy Signatures Map Evolution of Therapy-Related Myeloid Neoplasms
Authors: Diamond Benjamin , Ziccheddu Bachisio , Maclachlan Kylee , Taylor Justin , Boyle Eileen , Ossa Juan Arrango , Jahn Jacob , Affer Maurizio , Totiger Tulasigeri M. , Coffey David , Watts Justin , Lu Sydney X , Bolli Niccolò , Bolton Kelly , Park Jae H. , Landau Heather , Ganesh Karuna , McPherson Andrew , Sekeres Mikkael A. , Lesokhin Alexander , Chung David , Zhang Yanming , Ho Caleb , Roshal Mikhail , Tyner Jeffrey , Nimer Stephen , Papaemmanuil Elli , Usmani Saad , Morgan Gareth , Landgren Ola , Maura Francesco 
Published: April 2022

ABSTRACTPatients treated with cytotoxic therapies, including autologous stem cell transplantation, are at risk for developing therapy-related myeloid neoplasms1, 2. Pre-leukemic clones (i.e., clonal hematopoiesis) are detectable years before the development of these aggressive malignancies3-5, though the genomic events leading to transformation and expansion are not well-defined. Here, leveraging distinctive chemotherapy-associated mutational signatures6-12 from whole-genome sequencing data and targeted sequencing of pre-chemotherapy samples, we reconstruct the evolutionary life-history of 39 therapy-related myeloid malignancies. A dichotomy is revealed, in which neoplasms with evidence of chemotherapy-induced mutagenesis from platinum and melphalan are relatively hypermutated and enriched for complex structural variants (i.e., chromothripsis), while neoplasms with alternative exposures bear a similar profile to de novo acute myeloid leukemia. Using chemotherapy-associated mutational signatures as a temporal barcode in each patient’s life, we estimate that several complex events and genomic drivers are acquired after chemotherapy exposure. In the case of treatment with high-dose melphalan and autologous stem cell transplantation, we demonstrate that the procedure allows clonal hematopoiesis to escape chemotherapy exposure entirely, and to be reinfused to expand to malignancy. This information reveals a novel mode of malignant progression for therapy-related malignancies that is not reliant on direct mutagenesis or even exposure to chemotherapy, itself, and prompts further investigation into leukemia-permissive effects of cytotoxic drugs.
Relationships between mediolateral step modulation and clinical balance measures in people with chronic stroke
Authors: Howard Keith E. , Reimold Nicholas K. , Knight Heather L. , Embry Aaron E. , Knapp Holly A. , Agne Alexa A. , Jacobs Camden J. , Dean Jesse C. 
Published: April 2022

AbstractBackgroundMany people with chronic stroke (PwCS) exhibit walking balance deficits linked to increased fall risk and decreased balance confidence. One potential contributor to these balance deficits is a decreased ability to modulate mediolateral stepping behavior based on pelvis motion. This behavior, hereby termed mediolateral step modulation, is thought to be an important balance strategy but can be disrupted in PwCS.Research QuestionAre biomechanical metrics of mediolateral step modulation related to common clinical balance measures among PwCS?MethodsIn this cross-sectional study, 93 PwCS walked on a treadmill at their self-selected speed for 3-minutes. We quantified mediolateral step modulation for both paretic and non-paretic steps by calculating partial correlations between mediolateral pelvis displacement at the start of each step and step width (ρSW), mediolateral foot placement relative to the pelvis (ρFP), and final mediolateral location of the pelvis (ρPD) at the end of the step. We also assessed several common clinical balance measures (Functional Gait Assessment [FGA], Activities-specific Balance Confidence scale [ABC], self-reported fear of falling and fall history). We performed Spearman correlations to relate each biomechanical metric of step modulation to FGA and ABC scores. We performed Wilcoxon rank sum tests to compare each biomechanical metric between individuals with and without a fear of falling and a history of falls.ResultsOnly ρFP for paretic steps was significantly related to all four clinical balance measures; higher paretic ρFP values tended to be observed in participants with higher FGA scores, with higher ABC scores, without a fear of falling and without a history of falls. However, the strength of each of these relationships was only weak to moderate.SignificanceWhile the present results do not provide insight into causality, they justify future work investigating whether interventions designed to increase ρFP can improve clinical measures of post-stroke balance in parallel.
Diagnostic delay of Myositis: protocol for an integrated systematic review
Authors: Namsrai Tergel , Desborough Jane , Chalmers Anita , Lowe Christine , Cook Matthew , Phillips Christine , Parkinson Anne 
Published: April 2022

AbstractIdiopathic inflammatory myopathies (IIM) described as “inflammatory myositis”, are a heterogeneous group of rare muscular autoimmune diseases characterized by skeletal muscle inflammation. Its complex characteristics with lack of accurate diagnostic tests, unified classification system, and comprehensive widely used diagnostic criteria could lead to diagnostic delay. This study will review diagnostic delay in Myositis and provide an overview and clearer insight of patients’ experiences, causes and consequences of diagnostic delay in Myositis.Methods and analysisThe literature source will be a systematic search of PubMed/Medline, Scopus, ProQuest, and sources of grey literature, conducted from database inception to 15th of December 2021 without restrictions on publication date. All study types (qualitative and quantitative) except review articles, examining diagnostic delay, incorrect diagnosis, missed diagnosis or slow diagnosis of all types of myositis in all ages will be included. Evidence of patients’ experiences associated with diagnostic delay will also be examined. Studies in languages other than English, German and Indonesian will be excluded. Outcomes will be diagnostic delay time, patients’ experiences, and causes and consequences associated with diagnostic delay in Myositis. Two review authors will independently screen the titles and abstracts of search results against the inclusion criteria. The Mixed Methods Appraisal Tool (MMAT) will be used to appraise selected studies. Two independent authors will extract data using a pre-piloted data extraction tool. If sufficient quantitative data is available, a meta-analysis will be conducted along with subgroup analysis including pooled diagnostic delay in each type of Myositis. Qualitative data will be analysed in line with meta-aggregation methods. If data is insufficient, a narrative synthesis will be conducted.Ethics and disseminationAs a systematic review, ethical approval was not required. Findings of the study will be disseminated through publications in peer-reviewed journals, conferences, and symposia.PROSPERO Registration numberCRD42022289830Strengths and limitations of this studyThe protocol was developed in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines and the Cochrane Handbook for Systematic Reviews.Examination of both quantitative and qualitative literature will enable insight into the causes and consequences, and patients’ experiences associated with diagnostic delay of Myositis.In some case studies, it will be necessary to manually calculate diagnostic delay according to the date of symptom onset and the date of diagnosis.The primary limitation of this study is that it will not capture evidence that is not published, or from situations when an accurate diagnosis of Myositis is not made.The review will be limited to English, German, and Indonesian studies.
Liposome-assisted in-situ cargo delivery to artificial cells and cellular subcompartments
Authors: Xue Lin , Stephenson Anna B. , Gözen Irep 
Published: April 2022

AbstractWe report on liposome-mediated targeted delivery of membrane-impermeable constituents into surface-adhered giant lipid compartments, employed as artificial cells. Soluble cargo compounds are delivered by means of an open-space microfluidic device, which perfuses selected lipid compartments with loaded small unilamellar vesicles (SUVs) composed of cationic lipids. The SUV membranes fuse with the surface-adhered containers, merging their contents. We monitored the fusion process via Förster resonance energy transfer (FRET) by labeling both the membranes of the SUVs and the target compartments with a fluorophore pair. We established that, upon fusion, water-soluble dyes, fluorescently labeled genetic polymers, sugars and proteins carried by the SUVs can be successfully internalized at high yield. Finally, by transferring carbonic anhydrase (CA) to the giant lipid compartments, enzymatic hydrolysis of the prefluorescent carboxyfluorescein diacetate (CFDA) is demonstrated by the emission intensity increase emanating from the product carboxyfluorescein (CF). Spontaneous subcompartmentalization occurred during liposomal delivery of the enzyme, leading to CF formation in an organelle-like subcompartment. The reported targeted delivery technique enables chemical reactions and cell-free gene expression in synthetic cell models with unprecedented ease and precision, and opens pathways to protocell architectures with distinct functional subcompartments in the context of origins of life research.
ConsAlign: simultaneous RNA structural aligner based on rich transfer learning and thermodynamic ensemble model of alignment scoring
Authors: Tagashira Masaki 
Published: April 2022

AbstractMotivationTo capture structural homology in RNAs, predicting RNA structural alignments has been a fundamental framework around RNA science. Learning simultaneous RNA structural alignments in their rich scoring is an undeveloped subject because evaluating them is computationally expensive.ResultsWe developed ConsTrain—a gradient-based machine learning method for rich structural alignment scoring. We also implemented ConsAlign—a simultaneous RNA structural aligner composed of ConsTrain’s learned scoring parameters. To aim for better structural alignment quality, ConsAlign employs (1) transfer learning from well-defined scoring models and (2) the ensemble model between the ConsTrain model and a mature thermodynamic scoring model. Keeping comparable running time, ConsAlign demonstrated competitive alignment prediction quality among current RNA structural aligners.Availability and implementationOur code and our data are freely available at https://github.com/heartsh/consalign.Contactheartsh@heartsh.ioSupplementary informationSupplementary data are available at Bioinformatics