bluuebunny/crossref_metadata_2025_split huggingface dataset:
Future modalities to assess fracture healing
Authors: Lee Christopher , Copp Jonathan 
Published: March 2022

Abstract

Objectives:
Fracture healing remains a complex process routinely evaluated in clinical practice with sequential radiographs. Assessing the presence of union is a critical issue in patient care, with widespread implications in terms of overall decision-making and postoperative rehabilitation. Nonunion assessment, whether it be with radiographs or more advanced imaging, has far-reaching consequences for the patient in addition to the health care system. The purpose of this review was to explore new, emerging modalities for the assessment of fracture healing.

Methods:
A review of the current, relevant literature regarding the use of serologic markers and radiostereometric analysis was conducted, and the results were summarized.

Results:
Emerging techniques to assess fracture healing have been evaluated, including the use of serologic markers as well as radiostereometric analysis. Their potential applications extend beyond the simple assessment of a united fracture, with the capacity to predict nonunion at earlier phases of care.

Conclusions:
While early results appear promising, the current application of serologic markers and radiostereometric analysis as a means to assess fracture healing remains limited, and future larger-scale studies are needed to establish concrete and tailored guidelines for use.
Enhancing fracture repair: cell-based approaches
Authors: Wixted John , Challa Sravya , Nazarian Ara 
Published: March 2022

Abstract
Fracture repair is based both on the macrolevel modulation of fracture fragments and the subsequent cellular activity. Surgeons have also long recognized other influences on cellular behavior: the effect of the fracture or subsequent surgery on the available pool of cells present locally in the periosteum, the interrelated effects of fragment displacement, and construct stiffness on healing potential, patient pathophysiology and systemic disease conditions (such as diabetes), and external regulators of the skeletal repair (such as smoking or effect of medications). A wide variety of approaches have been applied to enhancing fracture repair by manipulation of cellular biology. Many of these approaches reflect our growing understanding of the cellular physiology that underlies skeletal regeneration. This review focuses on approaches to manipulating cell lineages, influencing paracrine and autocrine cell signaling, or applying other strategies to influence cell surface receptors and subsequent behavior. Scientists continue to evolve new approaches to pharmacologically enhancing the fracture repair process.
An in vivo rabbit joint injury model to measure trauma-induced coagulopathy and the effect of timing of administration of ketotifen fumarate on posttraumatic joint contracture
Authors: You Daniel , Maarouf Nadia , Hildebrand Kevin , Soo Andrea , Schneider Prism 
Published: March 2022

Abstract

Objectives:
Using a rabbit in vivo joint injury model, the primary objective of the study was to determine if a relationship exists between earlier time to initiation of ketotifen fumarate (KF) treatment and posttraumatic joint contracture (PTJC) reduction. The secondary objective was to determine if a coagulation response could be detected with serial thrombelastography (TEG) analysis following acute trauma in this model.

Methods:
PTJC of the knee were created in 25 skeletally mature, New Zealand White rabbits. Five groups of 5 animals were studied: a control group that received twice daily subcutaneous injections of normal saline and 4 treatment groups that received twice daily subcutaneous injections of KF (0.5 mg/kg) starting immediately, 1-, 2-, and 4-weeks post-injury. After 8 weeks of immobilization, flexion contractures were measured biomechanically. Serial TEG analysis was performed on the control group animals pre-injury and weekly post-injury.

Results:
The average joint contracture in the Control Group (43.1° ± 16.2°) was higher than all KF treatment groups; however, the differences were not statistically significant. The average joint contracture was lowest in the 2-week post-injury treatment group (29.4° ± 12.1°), although not statistically significant compared to the other treatment groups. Serial TEG analysis demonstrated significantly higher mean maximal amplitude (maximal amplitude = 68.9 ± 1.7 mm; P < .001), alpha-angle (81.9° ± 0.9°; P < .001), and coagulation index (4.5 ± 0.3; P < .001) 1-week post-injury, which normalized to pre-injury values by 5-weeks post-injury.

Conclusions:
The use of the mast cell stabilizer KF within 2 weeks of injury demonstrated a nonsignificant trend towards reducing joint contracture in a rabbit in vivo model of PTJC. TEG and the in vivo rabbit joint injury model may be valuable in future preclinical studies of venous thromboembolism prevention and furthering our understanding of the pathophysiology of posttraumatic hypercoagulability.
Modulation of LTCC Pathways by a Melusin Mimetic Increases Ventricular Contractility During LPS-Induced Cardiomyopathy
Authors: Arina Pietro , Sorge Matteo , Gallo Andrea , Di Mauro Vittoria , Vitale Nicoletta , Cappello Paola , Brazzi Luca , Barandalla-Sobrados Maria , Cimino James , Ranieri V. Marco , Altruda Fiorella , Singer Mervyn , Catalucci Daniele , Brancaccio Mara , Fanelli Vito 
Published: March 2022

ABSTRACT

Aim:
Sepsis-induced cardiomyopathy is commonplace and carries an increased risk of death. Melusin, a cardiac muscle-specific chaperone, exerts cardioprotective function under varied stressful conditions through activation of the AKT pathway. The objective of this study was to determine the role of melusin in the pathogenesis of lipopolysaccharide (LPS)-induced cardiac dysfunction and to explore its signaling pathway for the identification of putative therapeutic targets.

Methods and results:
Prospective, randomized, controlled experimental study in a research laboratory. Melusin overexpressing (MelOV) and wild-type (MelWT) mice were used. MelOV and MelWT mice were injected intraperitoneally with LPS. Cardiac function was assessed using trans-thoracic echocardiography. Myocardial expression of L-type calcium channel (LTCC), phospho-Akt and phospho-Gsk3-b were also measured. In separate experiments, wild-type mice were treated post-LPS challenge with the allosteric Akt inhibitor Arq092 and a mimetic peptide (R7W-MP) targeting the LTCC. The impact of these therapies on protein–protein interactions, cardiac function, and survival was assessed. MelOV mice had limited derangement in cardiac function after LPS challenge. Protection was associated with higher Akt and Gsk3-b phosphorylation and restored LTCC density. Pharmacological inhibition of Akt activity reversed melusin-dependent cardiac protection. Treatment with R7W-MP preserved cardiac function in wild-type mice after LPS challenge and significantly improved survival.

Conclusions:
This study identifies AKT/Melusin as a key pathway for preserving cardiac function following LPS challenge. The cell-permeable mimetic peptide (R7W-MP) represents a putative therapeutic for sepsis-induced cardiomyopathy.
Does patient preference for online or telephone follow-up impact on response rates and data completeness following injury?
Authors: Gabbe Belinda J. , Hart Melissa J. , Brown Amanda , McLellan Susan , Morgan Meredith J. , Beck Ben , de Steiger Richard S. , Cameron Peter A. 
Published: March 2022

BACKGROUND
Routine collection of patient-reported outcomes is needed to better understand recovery, benchmark between trauma centers and systems, and monitor outcomes over time. A key component of follow-up methodology is the mode of administration of outcome measures with multiple options available. We aimed to quantify patient preference and compare the response rates and data completeness for telephone and online completion in trauma patients.

METHODS
A registry-based cohort study of adult (16 years and older) patients registered to the Victorian State Trauma Registry and Victorian Orthopedic Trauma Outcomes Registry from April 2020 to December 2020 was undertaken. Survivors to discharge were contacted by telephone and offered the option of telephone or online completion of 6-month follow-up using the five-level EuroQol five-dimension (EQ-5D-5L) questionnaire and the 12-item World Health Organization Disability Assessment Schedule (WHODAS). The online and telephone groups were compared for differences in characteristics, follow-up rates, and data completeness. Multivariable logistic regression was used to identify predictors of choosing online completion.

RESULTS
Of the 3,886 patients, 51% (n = 1,994) chose online follow-up, and the follow-up rates were lower for online (77%), compared with telephone (89%), follow-up. Younger age, higher socioeconomic status, and preferred language other than English were associated with higher adjusted odds of choosing online completion. Admission to intensive care was associated with lower adjusted odds of choosing online completion. Completion rate for the EQ-5D-5L utility score was 97% for both groups. A valid total 12-WHODAS score could be calculated for 63% of online respondents compared with 86% for the telephone group.

CONCLUSION
More than half of trauma patients opted for online completion. Completion rates did differ depending on the questionnaire and telephone follow-up rates were higher. Nevertheless, given the wide diversity of the trauma population, the high rate of online uptake, and potential resource constraints, the study findings largely support the use of dual methods for follow-up.

LEVEL OF EVIDENCE
Prognostic/Epidemiological, Level III.
Advanced medical monitoring for the battlefield: A review on clinical applicability of compensatory reserve measurements for early and accurate hemorrhage detection
Authors: Convertino Victor A. , Cardin Sylvain 
Published: March 2022

ABSTRACT
Hemorrhagic shock remains the leading cause of mortality in civilian trauma and battlefield settings. The ability of combat medics and other military medical personnel to obtain early identification and assessment of a bleeding casualty is hampered by the use of standard vital signs that fail to provide early predictive indicators of the onset of shock because of compensatory mechanisms. Over the past decade, the emergence and application of new technologies that incorporate the use of artificial intelligence have revealed that continuous, real-time arterial waveform analysis (AWFA) reflects the recruitment of such compensatory mechanism. As such, AWFA can provide early hemorrhage detection and indication of the onset of overt shock compared with standard vital signs. In this review, we provide for the first time a summary of clinical data collected in patients with varying conditions of blood loss, sepsis, and resuscitation with direct comparison of AWFA and standard vital signs. Receiver operating characteristic area under the curve data clearly demonstrate that AWFA provides greater accuracy with early indicators for changes in blood volume compared with standard vital signs. A consistently greater sensitivity generated by AWFA compared with vital signs is associated with its ability to provide earlier hemorrhage detection, while higher specificity reflects its propensity to distinguish “poor” compensators (i.e., those with relatively low tolerance to blood loss) from “good” compensators. The data presented in this review demonstrate that integration of AWFA into medical monitoring capabilities has the potential to improve clinical outcomes of casualties by providing earlier and individualized assessment of blood loss and resuscitation.
Improvement of Mineral and Bone Disorders After Renal Transplantation
Authors: Ferreira Ana Carina , Mendes Marco , Silva Cecília , Cotovio Patrícia , Aires Inês , Navarro David , Caeiro Fernando , Ramos Rúben , Salvador Rute , Correia Bruna , Cabral Guadalupe , Nolasco Fernando , Ferreira Aníbal 
Published: March 2022

Background.
Posttransplant mineral and bone diseases are causes of fractures, and their association with cardiovascular events is being studied.

Methods.
We analyzed the evolution of biochemical, histological, and imaging parameters pre– and 1 y post–renal transplantation in 69 patients and correlated mineral and bone findings with coronary calcifications. At inclusion and after 12 mo, clinical data and echocardiographic findings were recorded, and laboratory evaluations, radiography of the pelvis and hands, and bone biopsy were performed. Noncontrast cardiac computed tomography was performed during the second evaluation.

Results.
Serum levels of fibroblast growth factor 23 and sclerostin decreased in all patients, parathyroid hormone levels decreased in 89.8% of patients, bone alkaline phosphatase levels decreased in 68.1% of patients, and alpha-Klotho levels increased in 65.2% of patients. More than half of the patients presented with renal osteodystrophy at both biopsies, but histological findings improved: a significant transition from high to normal or low turnover and no significant differences in volume, mineralization defect, or cortical porosity at the 2 evaluations. Alpha-Klotho, sclerostin, and bone alkaline phosphatase shifts affect bone changes. Neither echocardiographic findings nor vascular calcification scores differed between the 2 points. Both the pretransplant period (dialysis vintage, sclerostin, and low bone volume at baseline) and the maintenance of abnormalities in the posttransplant period (high turnover posttransplant) were the most reliable predictors of the severity of the coronary calcification percentile.

Conclusions.
Renal transplantation improved bone and mineral abnormalities. The pretransplant period determines the severity of calcification.
The Role of Procurement Biopsies in Kidney Acceptance Decision Making and Kidney Discard: Perceptions of Physicians, Nurse Coordinators, and OPO Staff and Directors
Authors: Schantz Karolina , Gordon Elisa J. , Lee Unsun , Rocha Maria , Friedewald John , Ladner Daniela P. , Becker Yolanda , Formica Richard , Reese Peter P. , Kaufman Dixon , Barah Masoud , Walker Marissa , Mehrotra Om , Viveros Dania , Mehrotra Sanjay 
Published: March 2022

Background.
Procurement biopsies suffer from challenges with quality and reproducibility and are linked to kidney discard. Nonetheless, procurement biopsies are obtained for the majority of kidneys in the United States, and biopsy findings are commonly relied upon in kidney acceptance decisions.

Methods.
We conducted in-depth, semistructured interviews with 30 surgeons, nephrologists, nurse coordinators, and organ procurement organization (OPO) staff and directors to assess perceptions of factors contributing to kidney discard and strategies to reduce kidney discard, with a focus on the role of procurement biopsies. Thematic analysis was used to analyze qualitative data.

Results.
Three main themes emerged: (1) participants emphasized the importance of biopsy findings in making acceptance decisions but expressed concerns about a lack of standardization and quality control; (2) participants reported large variations in the level of importance placed on biopsy findings, the level of reliance on glomerulosclerosis in particular, and the cutoffs used; and (3) participants disagreed about how often procurement biopsies should be taken, with some supporting stricter limits on which kidneys are biopsied and others preferring a biopsy for most kidney offers.

Conclusions.
These findings support the development of standard practices for which kidneys require biopsy, how the biopsy material is prepared, and how the biopsy is interpreted. Variability in kidney acceptance practices across centers and the use of biopsy findings in guiding recipient selection also lend support to policies to allocate kidneys with suboptimal histological findings to the centers that are willing to use such kidneys and the patients who could most benefit from such offers.
Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer’s disease
Authors: Rubinski Anna , Franzmeier Nicolai , Dewenter Anna , Luan Ying , Smith Ruben , Strandberg Olof , Ossenkoppele Rik , Dichgans Martin , Hansson Oskar , Ewers Michael ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: March 2022

AbstractIn Alzheimer’s disease (AD), pathologic tau gradually progresses from initially circumscribed predilection regions to closely connected cortical regions. The pattern of tau-deposition is of critical importance for the clinical expression of AD, but the factors that underlie region-dependent susceptibility and resistance to tau pathology remain elusive. Motivated by brain-autopsy findings suggesting late thinly myelinated regions are the first to develop tau pathology, we investigated whether the level of myelination in fiber-tracts and cortex is predictive of region-specific tau accumulation. To address this hypothesis, we combined MRI-derived template of normative myelin distribution with tau-PET imaging from two independent samples of AD-biomarker characterized participants. We found that higher myelinated cortical regions show lower tau-PET uptake in spatially corresponding areas and regions connected by highly myelinated fiber-tracts show lower rates of tau spreading. These findings were independent of amyloid-PET levels. Together, our findings suggest that higher myelination is an important resistance factor against tau pathology in AD.
Detecting eczema areas in digital images: an impossible task?
Authors: Hurault Guillem , Pan Kevin , Mokhtari Ricardo , Olabi Bayanne , Earp Eleanor , Steele Lloyd , Williams Hywel C. , Tanaka Reiko J. 
Published: March 2022

ABSTRACTAssessing the severity of atopic dermatitis (AD, or eczema) traditionally relies on a face-to-face assessment by healthcare professionals, and may suffer from inter- and intra-rater variability. With the expanding role of telemedicine, several machine learning algorithms have been proposed to automatically assess AD severity from digital images. Those algorithms usually detect and then delineate (“segment”) AD lesions before assessing lesional severity, and are trained using the data of AD areas detected by healthcare professionals. To evaluate the reliability of such data, we estimated the inter-rater reliability of AD segmentation in digital images.Four dermatologists independently segmented AD lesions in 80 digital images collected in a published clinical trial. We estimated the inter-rater reliability of the AD segmentation using the intra-class correlation coefficients (ICCs) at the pixel-level and the area-levels for different resolutions of the images. The average ICC was 0.45 (SE = 0.04) corresponding to a “poor” agreement between raters, while the degree of agreement for AD segmentation varied from image to image.The AD segmentation in digital images is highly rater-dependent even between dermatologists. Such limitations need to be taken into consideration when the AD segmentation data are used to train machine learning algorithms that assess eczema severity.
Culture and identification of a “Deltamicron” SARS-CoV-2 in a three cases cluster in southern France
Authors: Colson Philippe , Fournier Pierre-Edouard , Delerce Jeremy , Million Matthieu , Bedotto Marielle , Houhamdi Linda , Yahi Nouara , Bayette Jeremy , Levasseur Anthony , Fantini Jacques , Raoult Didier , Scola Bernard La 
Published: March 2022

ABSTRACTMultiple SARS-CoV-2 variants have successively, or concommitantly spread worldwide since summer 2020. A few co-infections with different variants were reported and genetic recombinations, common among coronaviruses, were reported or suspected based on co-detection of signature mutations of different variants in a given genome. Here we report three infections in southern France with a Delta 21J/AY.4-Omicron 21K/BA.1 “Deltamicron” recombinant. The hybrid genome harbors signature mutations of the two lineages, supported by a mean sequencing depth of 1,163-1,421 reads and mean nucleotide diversity of 0.1-0.6%. It is composed of the near full-length spike gene (from codons 156-179) of an Omicron 21K/BA.1 variant in a Delta 21J/AY.4 lineage backbone. Importantly, we cultured an isolate of this recombinant and sequenced its genome. It was observed by scanning electron microscopy. As it is misidentified with current variant screening qPCR, we designed and implemented for routine diagnosis a specific duplex qPCR. Finally, structural analysis of the recombinant spike suggested its hybrid content could optimize viral binding to the host cell membrane. These findings prompt further studies of the virological, epidemiological, and clinical features of this recombinant.
A qualitative examination of the factors affecting the adoption of injury focused wearable technologies in recreational runners
Authors: Lacey Aisling , Whyte Enda , O’Keefe Sinéad , O’Connor Siobhán , Moran Kieran 
Published: March 2022

AbstractPurposeUnderstanding users’ perceived usefulness and ease of use of technologies will influence their adoption and sustained use. The objectives of this study were to determine the metrics deemed important by runners for monitoring running-related injury (RRI) risk, and identify the barriers and facilitators to their use of injury focused wearable technologies.MethodsA qualitative focus group study was undertaken. Nine semi-structured focus groups with male (n=13) and female (n=14) recreational runners took place. Focus groups were audio and video recorded, and transcribed verbatim. Transcripts were thematically analysed. A critical friend approach was taken to data coding, and multiple methods of trustworthiness were executed.ResultsExcessive loading and inadequate recovery were deemed the most important risk factors to monitor for RRI risk. Other important factors included training activities, injury status and history, and running technique. The location and attachment method of a wearable device and the design of a smartphone application were identified as important barriers and facilitators, with receiving useful injury-related feedback identified as a further facilitator.ConclusionsOvertraining, training-related and individual- related risk factors are essential metrics that need to be monitored for RRI risk. RRI apps should include the metrics deemed important by runners, once there is supporting evidence- based research. The difficulty and/or ease of use of a device, and receiving useful feedback will influence the adoption of injury focused running technologies. There is a clear willingness from recreational runners to adopt injury focused wearable technologies whilst running.
A chronopharmacology-friendly multi-target therapeutics based on AI: the example of therapeutic hypothermia
Authors: Liu Fei , Jiang Xiangkang , Zhang Mao 
Published: March 2022

AbstractNowadays, the complexity of disease mechanisms and inadequacy of single-target therapies in restoring the biological system has inevitably instigated the strategy of multi-target therapeutics with the application of hybrid and chimeric drugs. However, the related method is still unable to solve the conflicts between targets or between drugs. With the release of high-precision protein structure prediction artificial intelligence (AI), large-scale high-precision protein structure prediction and docking become possible. In this article, we propose a multi-target drug discovery method. Then we take an example of therapeutic hypothermia (TH). We performed protein structure prediction for all targets of each group by AlphaFold2 and RoseTTAFold. QuickVina 2 is then used for molecular docking of the proteins and drugs. After docking, we use PageRank to get the rank of drugs and drug combinations of each group. Given the differences in the scoring of different proteins, the method can effectively avoid inhibiting beneficial proteins. So it’s friendly to chronopharmacology. This method also have potential in precision medicine for its high compatibility with bioinformatics.