Miracle-dz/UniFAR-FTUs huggingface dataset:
Measuring what matters: Why and how to include patient reported outcomes in clinical care and research on inborn errors of metabolism

Patient reported outcomes (PROs) are generally defined as ‘any report of the status of a patient's health condition that comes directly from the patient, without interpretation of the patient's response by a clinician or anyone else’. A broader definition of PRO also includes ‘any information on the outcomes of health care obtained directly from patients without modification by clinicians or other health care professionals’. Following this approach, PROs encompass subjective perceptions of patients on how they function or feel not only in relation to a health condition but also to its treatment as well as concepts such as health‐related quality of life (HrQoL), information on the functional status of a patient, signs and symptoms and symptom burden. PRO measurement instruments (PROMs) are mostly questionnaires and inform about what patients can do and how they feel. PROs and PROMs have not yet found unconditional acceptance and wide use in the field of inborn errors of metabolism. This review summarises the importance and usefulness of PROs in research, drug legislation and clinical care and informs about quality standards, development, and potential methodological shortfalls of PROMs. Inclusion of PROs measured with high‐quality, well‐selected PROMs into clinical care, drug legislation, and research helps to identify unmet needs, improve quality of care, and define outcomes that are meaningful to patients. The field of IEM should open to new methodological approaches such as the definition of core sets of variables including PROs to be systematically assessed in specific metabolic conditions and new collaborations with PRO experts, such as psychologists to facilitate the systematic collection of meaningful data.
The phenomenon of autonomous endosperm in sexual and apomictic plants

Abstract Endosperm is a key nutritive tissue that supports the developing embryo or seedling, and serves as a major nutritional source for human and livestock feed. In sexually-reproducing flowering plants, it generally develops after fertilization. However, autonomous endosperm (AE) formation (i.e. independent of fertilization) is also possible. Recent findings of AE loci/ genes and aberrant imprinting in native apomicts, together with a successful initiation of parthenogenesis in rice and lettuce, have enhanced our understanding of the mechanisms bridging sexual and apomictic seed formation. However, the mechanisms driving AE development are not well understood. This review presents novel aspects related to AE development in sexual and asexual plants underlying stress conditions as the primary trigger for AE. Both application of hormones to unfertilized ovules and mutations that impair epigenetic regulation lead to AE development in sexual Arabidopsis thaliana, which may point to a common pathway for both phenomena. Apomictic-like AE development under experimental conditions can take place due to auxin-dependent gene expression and/or DNA methylation.
Promising strategies for improving oral bioavailability of poor water-soluble drugs

ABSTRACT Introduction Oral administration of poorly water-soluble drugs (PWSDs) is generally related to low bioavailability, leading to high drug doses, multiple side effects, and low patient compliance. Thus, different strategies have been developed to increase drug solubility and dissolution in the gastrointestinal tract, opening new venues for these drugs. Areas covered This review outlines the current challenges in PWSD formulation development and the strategies to overcome the oral barriers and increase their solubility and bioavailability. Conventional strategies include altering crystalline and molecular structures and modifying oral solid dosage forms. In contrast, novel strategies comprise micro- and nanostructured systems. Recent representative studies involving how these strategies have improved the oral bioavailability of PWSDs were also reviewed and reported. Expert opinion New approaches to enhance PWSD bioavailability have sought to improve water solubility and dissolution rates, drug protection by overcoming biological barriers, and increased absorption. Still, only a handful of studies have focused on quantifying the increase in bioavailability. Improving the oral bioavailability of PWSDs remains an exciting unexplored field of research and has become an important issue for successfully developing pharmaceutical products.
Exploitation of the linear theory in the non-linear modelling of soft tissue

It is shown here how the linear theory of incompressible, transversely isotropic elasticity can positively influence the choice of strain-energy function of the non-linear theory so that the corresponding models of the mechanical response of biological soft tissue have a motivation based on mechanics. Specifically, it is shown that the structures of the linear theory have non-linear counterparts that could prove useful in the modelling of the moderate strain regime of soft tissue and that the recovery of the linear theory when the non-linear theory is restricted to infinitesimal deformations has important consequences for the choice of the strain-energy function.
Radiographic Incidence of Knee Osteoarthritis After Isolated ACL Reconstruction Versus Combined ACL and ALL Reconstruction: A Prospective Matched Study from the SANTI Study Group

Background: Combined anterior cruciate ligament (ACL) reconstruction (ACLR) and anterolateral ligament reconstruction (ALLR) have demonstrated reduced risk of graft rerupture as compared with isolated ACLR. However, concerns remain that the risk of osteoarthritis (OA) may be increased by the addition of ALLR. Purpose/Hypothesis: The aim of this study was to evaluate the incidence of OA with isolated ACLR in comparison with ACLR + ALLR at medium-term follow-up. We hypothesized that there would be no differences between the groups. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent ACLR + ALLR with hamstring tendon autograft between January 2011 and March 2012 were propensity matched to patients who underwent isolated ACLR with bone–patellar tendon–bone (BPTB) or hamstring tendon autograft in the same period. Medium-term radiographic evaluation was performed using the International Knee Documentation Committee (IKDC) radiographic OA grading scale, modified Kellgren-Lawrence grade, and the surface fit method to assess percentage of joint space narrowing. Clinical outcomes were assessed with the following measures: IKDC, Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm, Tegner, and ACL Return to Sport after Injury. Results: A total of 80 patients (42 ACLR + ALLR and 38 isolated ACLR) were analyzed with a mean follow-up of 104 months. There was no significant difference between groups for joint space narrowing in the medial or lateral tibiofemoral or lateral patellofemoral (PF) compartment. However, 36.8% in the isolated ACLR group versus 11.9% in the ACLR + ALLR group had narrowing of the medial PF compartment (P = .0118). A lateral meniscal tear increased the risk of lateral tibiofemoral narrowing by nearly 5 times (odds ratio, 4.9; 95% CI, 1.547-19.367; P = .0123). The risk of medial PF narrowing was >4-fold with an isolated ACLR (odds ratio, 4.8; 95% CI, 1.44-19.05; P = .0179). Between the isolated ACLR group and the ACLR + ALLR group, the secondary meniscectomy rate was 13.2% versus 11.9% (not significantly different). There was no difference between groups in KOOS, Tegner, or IKDC scores. There was also no difference between groups for grades of osteoarthritic change for any classification system. Patients who received a BPTB graft had medial PF joint narrowing in 66.7% of cases as compared with 11.9% in those who received ACLR + ALLR (P = 0.118). Conclusion: ACLR + ALLR did not increase the risk of OA in the lateral tibiofemoral compartment when compared with an isolated ACLR at medium-term follow-up. Isolated ACLR using BPTB was associated with a significantly increased risk of medial PF joint space narrowing. Registration: NCT05123456 (ClinicalTrials.gov identifier).
Vertebrate-tropism of a cressdnavirus lineage implicated by poxvirus gene capture

Significance A single family of cressdnaviruses is known to infect vertebrates, the Circoviridae. Here, we identified a second that has historically infected saurians, naming them the Draupnirviridae. The initial clue was that some draupnirviruses donated their Rep gene to poxviruses exclusively infecting birds and their relatives. Since this implied the donors also infected vertebrates, a search for draupnirvirus-derived endogenous viral elements was done in ~25,000 eukaryotic genome assemblies. This confirmed that some draupnirviruses infected saurian vertebrates as long ago as the Cretaceous Period, over 100 million years before present, and they still circulate today. We propose that their evolutionary path likely began with protist-infecting ancestors, followed by emergence in insects, and eventual transfer to vertebrates by blood feeders.
Beyond Magnification and Illumination: Ergonomics with a 3D Exoscope in Lumbar Spine Microsurgery to Reduce Musculoskeletal Injuries

The risk of musculoskeletal injuries (MSIs) increases over years of practice which may lead to career‐ending among surgeons. Exoscopes represent a new generation of imaging systems that help surgeons operate in a more comfortable posture. This article aimed to assess advantages and limitations, especially ergonomics with a 3D exoscope in lumbar spine microsurgery versus an operating microscope (OM) to reduce MSIs.
Brainstorming to concept maps: Developing ontological categories for energy

Energy is an abstract concept that is poorly understood at the middle school level. Traditionally the use of imposed definitions and terminology, which have little relevance for students, has given the topic of energy a reputation for being boring and dry. Students’ preconceived understanding of the energy concept, derived from their own experiences was the starting point of this study. Students were required to analyse their own ideas on energy, brainstorm a variety of fields relating to the topic of energy and construct concept maps and Venn diagrams to represent their understanding. The schools’ policy of integrating laptop computers in middle school provided additional tools to achieve the objectives of the science unit on energy. Guided development of students’ schema from very specific examples to general categories helped to develop new ontological schema in the students’ mental organisation of their knowledge and ideas relating to energy. This constructivist approach formed the groundwork to the students learning processes which were dependent on the social interaction of students, students listening to each other, working as a team, the visual record, the linking of concepts and ideas, and the integration of new ideas with their existing ideas. Brainstorming to concept maps: Developing ontological categories for energy
Bacterial Etiology in Subacute Cough

Although postinfectious etiology is the most common cause of subacute cough, there are insufficient data on the epidemiology of associated bacterial infections. We aimed to identify the etiology of bacterial detection in subjects with subacute cough. A multicenter prospective observational study of 142 patients with postinfectious subacute cough was performed between August 2016 and December 2017 in Korea. We obtained 2 nasal swabs from each patient and used a multiplex bacterial polymerase chain reaction (PCR) kit that simultaneously detects Bordetella pertussis, Chlamydophila pneumoniae, Haemophilus influenzae, Legionella pneumophilia, Mycoplasma pneumoniae, and Streptococcus pneumoniae. About 29% (n = 41) of patients with subacute cough were positive for bacterial PCR in nasal swabs. The most common bacteria detected by bacterial PCR was H. influenzae (n = 19, 13.4%), followed by S. pneumoniae (n = 18, 12.7%), B. pertussis (n = 7, 4.9%), M. pneumoniae (n = 3, 2.1%), L. pneumophilia (n = 2, 1.4%), and C. pneumoniae (n = 1, 0.7%). Nine patients had dual positivity for the PCR. In conclusion, bacterial PCR was positive in the nasal swabs of about 29% of subjects with subacute cough, including 5% of positive PCR results for B. pertussis.
Associations between sleep characteristics, chronotype and body mass index among Chinese college freshmen

ABSTRACT Research indicates that sleep problem is a behavioral risk factor of obesity. However, few research have applied a multi-dimensional approach to investigate the relationship between sleep health and adiposity. Therefore, the current study aimed to examine the associations of sleep characteristics (duration, quality) and chronotype with overweight/obesity as measured by body mass index. Data were obtained from 2014 college students from the Dali University in the Yunnan province of China in the year 2021. Sleep characteristics and chronotype were measured using self-reported questionnaires. The presence of overweight/obesity was assessed by anthropometric measurements. Multiple logistic regression models and restricted cubic spline hazard models were established to examine associations between sleep characteristics, chronotype and adiposity. After adjusting for demographic characteristics and other obesity-related behavioral risk factors, evening type was positively associated with overweight/obesity, and an L-shaped dose-effect relationship was observed between chronotype scores and the presence of overweight/obesity. However, sleep duration and quality were not associated with the presence of overweight/obesity in the logistic regression models and restrictive cubic splines models. This study indicated that Chinese college students who had the evening chronotype were more likely to be affected by overweight/obesity. Chronotype as an important dimension of sleep health should be incorporated in obesity intervention programs.
Monomeric C‐reactive protein: A novel biomarker predicting neurodegenerative disease and vascular dysfunction

Circulating C‐reactive protein (pCRP) concentrations rise dramatically during both acute (e.g., following stroke) or chronic infection and disease (e.g., autoimmune conditions such as lupus), providing complement fixation through C1q protein binding. It is now known, that on exposure to the membranes of activated immune cells (and microvesicles and platelets), or damaged/dysfunctional tissue, it undergoes lysophosphocholine (LPC)‐phospholipase‐C‐dependent dissociation to the monomeric form (mCRP), concomitantly becoming biologically active. We review histological, immunohistochemical, and morphological/topological studies of post‐mortem brain tissue from individuals with neuroinflammatory disease, showing that mCRP becomes stably distributed within the parenchyma, and resident in the arterial intima and lumen, being “released” from damaged, hemorrhagic vessels into the extracellular matrix. The possible de novo synthesis via neurons, endothelial cells, and glia is also considered. In vitro, in vivo, and human tissue co‐localization analyses have linked mCRP to neurovascular dysfunction, vascular activation resulting in increased permeability, and leakage, compromise of blood brain barrier function, buildup of toxic proteins including tau and beta amyloid (Aβ), association with and capacity to “manufacture” Aβ‐mCRP‐hybrid plaques, and, greater susceptibility to neurodegeneration and dementia. Recently, several studies linked chronic CRP/mCRP systemic expression in autoimmune disease with increased risk of dementia and the mechanisms through which this occurs are investigated here. The neurovascular unit mediates correct intramural periarterial drainage, evidence is provided here that suggests a critical impact of mCRP on neurovascular elements that could suggest its participation in the earliest stages of dysfunction and conclude that further investigation is warranted. We discuss future therapeutic options aimed at inhibiting the pCRP‐LPC mediated dissociation associated with brain pathology, for example, compound 1,6‐bis‐PC, injected intravenously, prevented mCRP deposition and associated damage, after temporary left anterior descending artery ligation and myocardial infarction in a rat model.
Facilitators of palliative care quality improvement team cohesion

Background The Palliative Care: Promoting Access and Improvement of the Cancer Experience (PC-PAICE) initiative is a team-based, palliative care (PC) quality improvement (QI) project working to promote high-quality PC in India. As a PC QI initiative, PC-PAICE implementation relied upon building interdisciplinary teams, providing the ideal context for understanding facilitators of team cohesion that compelled clinical, organizational, and administrative team members to work together. There is an opportunity to leverage the intersection between QI implementation and organizational theory to inform and improve implementation science. Purpose As a subaim of a larger implementation evaluation, we aimed to identify facilitators of team cohesion within QI implementation context. Methodology A quota sampling approach captured the perspectives of 44 stakeholders across three strata (organizational leaders, clinical leaders, and clinical team members) from all seven sites through a semistructured interview guide informed by the Consolidated Framework for Implementation Research (CFIR). We used a combination of inductive and deductive approaches informed by organizational theory to identify facilitators. Result We identified three facilitators of PC team cohesion: (a) balancing formalization and flexibility around team roles, (b) establishing widespread awareness of the QI project, and (c) prioritizing a nonhierarchical organizational culture. Practice Implications Leveraging CFIR to analyze PC-PAICE stakeholder interviews created a data set conducive to understanding complex multisite implementation. Layering role and team theory to our implementation analysis helped us identify facilitators of team cohesion across levels within the team (bounded team), beyond the team (teaming), and surrounding the team (culture). These insights demonstrate the value of team and role theories in implementation evaluation efforts.
A Fluid Self-Concept: How the Brain Maintains Coherence and Positivity across an Interconnected Self-Concept While Incorporating Social Feedback

People experience instances of social feedback as interdependent with potential implications for their entire self-concept. How do people maintain positivity and coherence across the self-concept while updating self-views from feedback? We present a network model describing how the brain represents the semantic dependency relations among traits and uses this information to avoid an overall loss of positivity and coherence. Both male and female human participants received social feedback during a self-evaluation task while undergoing functional magnetic resonance imaging. We modeled self-belief updating by incorporating a reinforcement learning model within the network structure. Participants learned more rapidly from positive than negative feedback and were less likely to change self-views for traits with more dependencies in the network. Further, participants back propagated feedback across network relations while retrieving prior feedback on the basis of network similarity to inform ongoing self-views. Activation in ventromedial prefrontal cortex (vmPFC) reflected the constrained updating process such that positive feedback led to higher activation and negative feedback to less activation for traits with more dependencies. Additionally, vmPFC was associated with the novelty of a trait relative to previously self-evaluated traits in the network, and angular gyrus was associated with greater certainty for self-beliefs given the relevance of prior feedback. We propose that neural computations that selectively enhance or attenuate social feedback and retrieve past relevant experiences to guide ongoing self-evaluations may support an overall positive and coherent self-concept. SIGNIFICANCE STATEMENT We humans experience social feedback throughout our lives, but we do not dispassionately incorporate feedback into our self-concept. The implications of feedback for our entire self-concept plays a role in how we either change or retain our prior self-beliefs. In a neuroimaging study, we find that people are less likely to change their beliefs from feedback when the feedback has broader implications for the self-concept. This resistance to change is reflected in processing in the ventromedial prefrontal cortex, a region that is central to self-referential and social cognition. These results are broadly applicable given the role that maintaining a positive and coherent self-concept plays in promoting mental health and development throughout the lifespan.
Bringing Structure to Cell Biology with Cryo-Electron Tomography

Recent advances in cryo-electron microscopy have marked only the beginning of the potential of this technique. To bring structure into cell biology, the modality of cryo-electron tomography has fast developed into a bona fide in situ structural biology technique where structures are determined in their native environment, the cell. Nearly every step of the cryo-focused ion beam-assisted electron tomography (cryo-FIB-ET) workflow has been improved upon in the past decade, since the first windows were carved into cells, unveiling macromolecular networks in near-native conditions. By bridging structural and cell biology, cryo-FIB-ET is advancing our understanding of structure–function relationships in their native environment and becoming a tool for discovering new biology.
Modal theory for recursive time-stepping numerical methods

Numerical time-domain methods have been applied extensively to solve various electromagnetic problems including scattering and radiating problems. The most widely used approaches are the finite-difference time-domain (FD-TD) method and the transmission-line-matrix (TLM) method due to the simplicity of their algorithms. The solutions of these two techniques have been shown to be the superposition of discrete eigenmodes, that is, the numerical solutions can be eigenmodally decomposed. In th the present paper, general eigenmodal formulations of numerical methods are discussed and compositions of numerical solutions are analyzed. It is concluded that solutions of any time-stepping recursive scheme are essentially solutions of an eigenvalue system. As a result, properties of a time-stepping recursive scheme, for example, numerical stability, can be studied. <<ETX>>
High-Altitude Cloud Effects on Airborne Electro-Optical Sensor Performance

Abstract A modeling approach is proposed to predict the impact of high-altitude clouds on the detection performance of an airborne electro-optical surveillance sensor. The sensor is dedicated to target detection, and it may be disturbed by cloud presence along the line of sight. The targets are supposed to be dim artificial sources in the atmosphere or stars, and the viewing conditions lead to lines of sight close to horizontal paths. The model is suitable to determine sensor performance for various locations in the earth’s atmosphere and for different seasons. It is based on cloud statistics data determined by the inversion of NOAA satellite observations. Computations of clear line-of-sight probabilities are based on geometric and statistical approaches, and the major hypothesis used here is that all clouds can be considered opaque. Seasonal and diurnal/nocturnal cloud cover variations strongly change the probability of a clear line of sight for a fixed viewing geometry, and the maximal range without clo.
Hydrodynamic stability and breakdown of the viscous regime over riblets

The interaction of the overlying turbulent ﬂow with a riblet surface and its impact ondrag reduction are analysed. The ‘viscous regime’ of vanishing riblet spacing, in whichthe drag reduction produced by the riblets is proportional to their size, is reasonablywell understood, but this paper focuses on the behaviour for spacings