bluuebunny/crossref_metadata_2025_split huggingface dataset:
Harnessing autophagy to fight SARS‐CoV‐2: An update in view of recent drug development efforts
Authors: Rein Theo 
Published: October 2021

AbstractDrug repurposing is an attractive option for identifying new treatment strategies, in particular in extraordinary situations of urgent need such as the current coronavirus disease 2019 (Covid‐19) pandemic. Recently, the World Health Organization announced testing of three drugs as potential Covid‐19 therapeutics that are known for their dampening effect on the immune system. Thus, the underlying concept of selecting these drugs is to temper the potentially life‐threatening overshooting of the immune system reacting to severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection. This viewpoint discusses the possibility that the impact of these and other drugs on autophagy contributes to their therapeutic effect by hampering the SARS‐CoV‐2 life cycle.
The effects of blood in self‐injurious cutting: Positive and negative affect regulation
Authors: Stacy Stephanie E. , Pepper Carolyn M. , Clapp Joshua D. , Reyna Alejandra H. 
Published: October 2021

AbstractObjectiveSeeing one's own blood may be a factor in affect regulation in nonsuicidal self‐injury (NSSI). This study examined changes in a negative (NA) and positive affect (PA) in response to a finger prick eliciting a small drop of participants' blood.MethodsTwo groups (NSSI; N = 56 and Control; N = 70) of undergraduate students were randomly assigned to receive a finger prick and look at blood, receive a finger prick and not look at blood, or receive a sham finger prick. Following a mood induction, participants completed the PANAS three times: Time 1 (pre mood‐induction, baseline), Time 2 (post‐mood induction), and Time 3 (post‐finger prick condition), and a Pain Severity Scale.ResultsA significant three‐way interaction revealed that the NSSI: Blood Group had an increased positive effect between Time 2 and Time 3.ConclusionBlood serves an important function in NSSI and requires additional research to fully understand the relationship.
Suicide attempts among adults denying active suicidal ideation: An examination of the relationship between suicidal thought content and suicidal behavior
Authors: Wastler Heather M. , Bryan AnnaBelle O. , Bryan Craig J. 
Published: October 2021

AbstractObjectivesThe purpose of the current study was to examine the possibility that there are multiple pathways to suicidal behavior by conducting a fine‐grained investigation of the relationship between suicidal thought content and suicidal behavior.MethodsSix thousand two hundred US adults completed self‐report measures of suicidal thoughts and behaviors. Descriptive statistics and logistic regression were used to examine the relationship between suicidal thoughts and behaviors.ResultsAbout 36.0% of participants with a lifetime suicide attempt denied ever experiencing any active suicidal thoughts and 11.0% denied ever experiencing any suicidal thoughts; 53.8% of recent attempters denied recent active suicidal thoughts and 22.6% denied any recent suicidal thoughts. Additionally, the sole presence of passive suicidal ideation was associated with increased odds of lifetime and past‐month suicide attempts.ConclusionsThese findings suggest that there are likely multiple pathways to suicide, some of which do not involve progressively worsening suicidal thoughts.
Multidirectional focus measure for accurate three‐dimensional shape recovery of microscopic objects
Authors: Shim Seong‐O 
Published: October 2021

AbstractShape from focus (SFF) is a technique to recover the shape of an object from multiple images taken at various focus settings. Most of conventional SFF techniques compute focus value of a pixel by applying one of focus measure operators on neighboring pixels on the same image frame. However, in the optics with limited depth of field, neighboring pixels of an image have different degree of focus for curved objects, thus the computed focus value does not reflect the accurate focus level of the pixel. Ideally, an accurate focus value of a pixel needs to be measured from the neighboring pixels lying on tangential plane of the pixel in image space. In this article, a tangential plane on each pixel location (i, j) in image sensor is searched by selecting one of five candidate planes based on the assumption that the maximum variance of focus values along the optical axis is achieved from the neighborhood lying on tangential plane of the pixel (i, j). Then, a focus measure operator is applied on neighboring pixels lying on the searched plane. The experimental results on both the synthetic and real microscopic objects show the proposed method produces more accurate three‐dimensional shape in comparison to conventional SFF method that applies focus measures on original image planes.
Cell trafficking and regulation of osteoblastogenesis by extracellular vesicle associated bone morphogenetic protein 2
Authors: Yerneni Saigopalakrishna S. , Adamik Juraj , Weiss Lee E. , Campbell Phil G. 
Published: October 2021

AbstractExtracellular vesicles (EVs) are characterized by complex cargo composition and carry a wide array of signalling cargo, including growth factors (GFs). Beyond surface‐associated GFs, it is unclear if EV intralumenal growth factors are biologically active. Here, bone morphogenetic protein‐2 (BMP2), loaded directly into the lumen of EVs designated engineered BMP2‐EVs (eBMP2‐EVs), was comprehensively characterized including its regulation of osteoblastogenesis. eBMP2‐EVs and non‐EV ‘free’ BMP2 were observed to similarly regulate osteoblastogenesis. Furthermore, cell trafficking experiments suggest rapid BMP2 recycling and its extracellular release as ‘free’ BMP2 and natural occurring BMP2‐EVs (nBMP2‐EVs), with both being osteogenic. Interestingly, BMP2 occurs on the EV surface of nBMP2‐EVs and is susceptible to proteolysis, inhibition by noggin and complete dissociation from nBMP2‐EVs over 3 days. Whereas, within the eBMP2‐EVs, BMP2 is protected from proteolysis, inhibition by noggin and is retained in EV lumen at 100% for the first 24 h and ∼80% after 10 days. Similar to ‘free’ BMP2, bioprinted eBMP2‐EV microenvironments induced osteogenesis in vitro and in vivo in spatial registration to the printed patterns. Taken together, BMP2 signalling involves dynamic BMP2 cell trafficking in and out of the cell involving EVs, with distinct differences between these nBMP2‐EVs and eBMP2‐EVs attributable to the BMP2 cargo location with EVs. Lastly, eBMP2‐EVs appear to deliver BMP2 directly into the cytoplasm, initiating BMP2 signalling within the cell, bypassing its cell surface receptors.
Evaluation of Hepatic Iron Overload Using a Contemporary 0.55 T MRI System
Authors: Campbell‐Washburn Adrienne E. , Mancini Christine , Conrey Anna , Edwards Lanelle , Shanbhag Sujata , Wood John , Xue Hui , Kellman Peter , Bandettini W. Patricia , Thein Swee Lay 
Published: October 2021

BackgroundMRI T2* and R2* mapping have gained clinical acceptance for noninvasive assessment of iron overload. Lower field MRI may offer increased measurement dynamic range in patients with high iron concentration and may potentially increase MRI accessibility, but it is compromised by lower signal‐to‐noise ratio that reduces measurement precision.PurposeTo characterize a high‐performance 0.55 T MRI system for evaluating patients with liver iron overload.Study TypeProspective.PopulationForty patients with known or suspected iron overload (sickle cell anemia [n = 5], ß‐thalassemia [n = 3], and hereditary spherocytosis [n = 2]) and a liver iron phantom.Field strength/sequenceA breath‐held multiecho gradient echo sequence at 0.55 T and 1.5 T.AssessmentPatients were imaged with T2*/R2* mapping 0.55 T and 1.5 T within 24 hours, and 16 patients returned for follow‐up exams within 6–16 months, resulting in 56 paired studies. Liver T2* and R2* measurements and standard deviations were compared between 0.55 T and 1.5 T and used to validate a predictive model between field strengths. The model was then used to classify iron overload at 0.55 T.Statistical TestsLinear regression and Bland–Altman analysis were used for comparisons, and measurement precision was assessed using the coefficient of variation. A P‐value < 0.05 was considered statistically significant.ResultsR2* was significantly lower at 0.55 T in our cohort (488 ± 449 s−1 at 1.5 T vs. 178 ± 155 s−1 at 0.55 T, n = 56 studies) and in the patients with severe iron overload (937 ± 369 s−1 at 1.5 T vs. 339 ± 127 s−1 at 0.55 T, n = 23 studies). The coefficient of variation indicated reduced precision at 0.55 T (3.5 ± 2.2% at 1.5 T vs 6.9 ± 3.9% at 0.55 T). The predictive model accurately predicted 1.5 T R2* from 0.55 T R2* (Bland Altman bias = −6.6 ± 20.5%). Using this model, iron overload at 0.55 T was classified as: severe R2* > 185 s−1, moderate 81 s−1 < R2* < 185 s−1, and mild 45 s−1 < R2* < 91 s−1.Data ConclusionWe demonstrated that 0.55 T provides T2* and R2* maps that can be used for the assessment of liver iron overload in patients.Evidence Level2Technical EfficacyStage 2
Transfer Learning Strategy Based on Unsupervised Learning and Ensemble Learning for Breast Cancer Molecular Subtype Prediction Using Dynamic Contrast‐Enhanced MRI
Authors: Sun Rong , Hou Xuewen , Li Xiujuan , Xie Yuanzhong , Nie Shengdong 
Published: October 2021

BackgroundImaging‐driven deep learning strategies focus on training from scratch and transfer learning. However, the performance of training from scratch is often impeded by the lack of large‐scale labeled training data. Additionally, owing to the differences between source and target domains, analyzing medical image tasks satisfactorily via transfer learning based on ImageNet is difficult.PurposeTo investigate two transfer learning algorithms for breast cancer molecular subtype prediction (luminal and non‐luminal) based on unsupervised pre‐training and ensemble learning: M_EL and B_EL, using malignant and benign datasets as the source domain, respectively.Study TypeRetrospective.PopulationEight hundred and thirty‐three female patients with histologically confirmed breast lesions (567 benign and 266 malignant cases) were selected. In the 5‐fold cross‐validation, the malignant cohort was randomly divided into 5 subsets to form a training set (80%) and a validation set (20%).Field Strength/Sequence3.0 T, dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) using T1‐weighted high‐resolution isotropic volume examination.AssessmentFirst, three datasets acquired at different times post‐contrast were preprocessed as unlabeled source domains. Second, three baseline networks corresponding to the different MRI post‐contrast phases were built, optimized by a combination of mutual information maximization between high‐ and low‐level representations and prior distribution constraints. Next, the pre‐trained networks were fine‐tuned on the labeled target domain. Finally, prediction results were integrated using weighted voting‐based ensemble learning.Statistical TestsMean accuracy, precision, specificity, and area under receiver operating characteristic curve (AUC) were obtained with 5‐fold cross‐validation. P < 0.05 was considered to be statistically significant.ResultsCompared with a convolutional long short‐term memory network, pre‐trained VGG‐16, VGG‐19, and DenseNet‐121 from ImageNet, M_EL and B_EL exhibited significantly more optimized prediction performance (specificity: 90.5% and 89.9%; accuracy: 82.6% and 81.1%; precision: 91.2% and 90.9%; AUC: 0.836 and 0.823, respectively).Data ConclusionTransfer learning based on unsupervised pre‐training may facilitate automatic prediction of breast cancer molecular subtypes.Level of Evidence3Technical EfficacyStage 2
Q‐Dixon and GRAPPATINI T2 Mapping Parameters: A Whole Spinal Assessment of the Relationship Between Osteoporosis and Intervertebral Disc Degeneration
Authors: Li Xiangwen , Xie Yuxue , Lu Rong , Zhang Yuyang , Li Qing , Kober Tobias , Hilbert Tom , Tao Hongyue , Chen Shuang 
Published: October 2021

BackgroundThe relationship between osteoporosis and intervertebral disc (IVD) degeneration remains controversial. Novel quantitative Dixon (Q‐Dixon) and GRAPPATINI T2 mapping techniques have shown potential for evaluating the biochemical components of the spine.PurposeTo investigate the correlation of osteoporosis with IVD degeneration in postmenopausal women.Study TypeProspective.SubjectsA total of 105 postmenopausal females (mean age, 65 years; mean body mass index, 26 kg/m2).Field Strength/Sequence3 T; sagittal; 6‐echo Q‐Dixon, multiecho spin‐echo GRAPPATINI T2 mapping, turbo spin echo (TSE) T1‐weighted and TSE T2‐weighted sequences.AssessmentThe subjects were divided into normal (N = 47), osteopenia (N = 28), and osteoporosis (N = 30) groups according to quantitative computed tomography examination. The Pfirrmann grade of each IVD was obtained. Region of interest analysis was performed separately by two radiologists (X.L., with 10 years of experience, and S.C., with 20 years of experience) on a fat fraction map and T2 map to calculate the bone marrow fat fraction (BMFF) from the L1 to L5 vertebrae and the T2 values of each adjacent IVD separately.Statistical TestsOne‐way analysis of variance, post‐hoc comparisons, and Kruskal–Wallis H tests were performed to evaluate the differences in the magnetic resonance imaging parameters between the groups. The relationships between BMFF and the IVD features were analyzed using the Spearman correlation analysis and linear regression models.ResultsThere were significant differences in BMFF among the three groups. The osteoporosis group had higher BMFF values (64.5 ± 5.9%). No significant correlation was found between BMFF and Pfirrmann grade (r = 0.251, P = 0.06). BMFF was significantly negatively correlated with the T2 of the adjacent IVD from L1 to L3 (r = −0.731; r = −0.637; r = −0.547), while significant weak correlations were found at the L4 to L5 levels (r = −0.337; r = −0.278).Data ConclusionThis study demonstrated that osteoporosis is associated with IVD degeneration.Level of Evidence2Technical EfficacyStage 4
Better detection of Torque teno virus in children with leukemia by metagenomic sequencing than by quantitative PCR
Authors: Leijonhufvud Gustaf , Bajalan Amanj , Teixeira Soratto Tatiany Aparecida , Gustafsson Britt , Bogdanovic Gordana , Bjerkner Annelie , Allander Tobias , Ljungman Gustaf , Andersson Björn 
Published: October 2021

AbstractTorque teno virus (TTV) is a group of chronically persisting viruses with a short circular DNA genome. TTV demonstrates a wide sequence diversity and a large majority of humans are chronically infected by one or more types of TTV. As TTV is ubiquitous, and viral replication correlates with immune status, TTV has been studied as a marker to assess global functional immune competence in transplant recipients. Most studies of the prevalence, amounts, and variation in TTV have been performed using PCR assays. We here present a comparison of the most frequently used quantitative PCR (qPCR) assay for TTV with shotgun metagenomic sequencing for detection and characterization of TTV in a cohort of pediatric cancer patients. The results show that TTV is more common than the qPCR assays indicate, and analysis of the TTV genome sequences indicate that a qPCR with primers and probe designed on a conserved region of the TTV genome may fail to detect some of the TTV strains found in this study.
Thin patient‐specific clavicle fracture fixation plates can mechanically outperform commercial plates: An in silico approach
Authors: Vancleef Sanne , Wesseling Mariska , Duflou Joost R. , Nijs Stefaan , Jonkers Ilse , Vander Sloten Jos 
Published: October 2021

AbstractCurrent fixation plates used to operatively stabilize clavicular fractures are suboptimal, leading to reoperation rates up to 53%. Plate irritation, which can be caused by a poor geometric fit and plate thickness, has been found to be an important factor for reoperation. Moreover, muscle attachment sites (MAS) have to be detached occasionally. To improve current surgical clavicle fracture treatment with plate osteosynthesis, a change in plate design is required. The goal of this study was to design a patient‐specific clavicle fracture fixation plate that includes geometrical optimization and stiffness determination. Its biomechanical performance has been compared with a commercial plate by examining the geometric fit, anatomical outline, stresses and interfragmentary motion using a finite element analysis with physiological loading and boundary conditions. Evaluation showed a better geometrical fit of the patient‐specific plate as well as an improved fracture reduction. Displacements between fracture fragments were lower in case of the patient‐specific plate, both when a fracture gap and no fracture gap were present. Results indicate a superior mechanical performance in terms of all investigated outcomes of the patient‐specific plate compared to the commercial plate, while better aligning with the patient‐specific geometry and without the need for MAS release. Due to the patient‐specific geometry and reduced thickness, these fixation plates are expected to decrease the operation time, as intraoperative contouring will become irrelevant, and to decrease reoperation rates as implant irritation will be minimized.
Pulsed electromagnetic field therapy alters early healing in a rat model of rotator cuff injury and repair: Potential mechanisms
Authors: Huegel Julianne , Chan Peter Y. W. , Weiss Stephanie N. , Nuss Courtney A. , Raja Harina , Waldorff Erik I. , Zhang Nianli , Ryaby James T. , Soslowsky Louis J. , Kuntz Andrew F. 
Published: October 2021

AbstractRotator cuff repair failure remains common due to poor tendon healing, particularly at the enthesis. We previously showed that pulsed electromagnetic field (PEMF) therapy improved the mechanical properties of the rat supraspinatus tendon postoperatively. However, little is known about the mechanisms behind PEMF‐dependent contributions to improved healing in this injury model. The objective of this study was to determine the influence of PEMF treatment on tendon gene expression and cell composition, as well as bone microarchitecture and dynamic bone metabolism during early stages of healing. We hypothesized that PEMF treatment would amplify tendon‐healing related signaling pathways while mitigating inflammation and improve bone metabolism at the repair site. Rats underwent rotator cuff injury and repair followed by assignment to either control (non‐PEMF) or PEMF treatment groups. Gene and protein expression as well as tendon and bone histological assessments were performed 3, 7, 14, 21, and 28 days after injury. Gene expression data demonstrated an upregulation in the bone morphogenetic protein 2 signaling pathway and increases in pro‐osteogenic genes at the insertion, supporting important processes to re‐establish the tendon‐bone interface. PEMF also downregulated genes related to a fibrotic healing response. Anti‐inflammatory effects were demonstrated by both gene expression and macrophage phenotype. PEMF significantly increased the rate of kinetic bone formation directly adjacent to the tendon enthesis as well as the number of cuboidal surface osteoblasts (active osteoblasts) in the humeral head. This study has provided insight into how PEMF affects cellular and molecular processes in the supraspinatus tendon and adjacent bone after injury and repair.
Relation between diameter of a lateral screw and pull‐out strength in distal clavicle fracture in plates with different geometry: A cadaveric biomechanical study
Authors: Yoon Tae‐Hwan , Choi Chong‑Hyuk , Choi Yun‐Rak , Ju Hun‐Jin , Chun Yong‐Min 
Published: October 2021

AbstractPlate fixation has recently gained popularity among the various surgical methods used to treat Neer type II distal clavicle fractures. The use of a low‐profile distal clavicle locking plate is logically considered a better option when there is no significant difference in the fixation strength between insertions of 3.5‐ and 2.7‐mm diameter screws. Therefore, the purpose of this biomechanical study was to investigate any differences in fixation strength among varying sizes of screws that are used to treat distal clavicle fractures. The study was performed with 20 paired shoulder girdles from 10 fresh frozen cadavers. To create a type IIA fracture of Neer classification, osteotomy was performed perpendicularly to the longitudinal axis of the clavicle at the medial end point of the conoid ligament. Two custom‐made fixtures designed to be attached to both upper and lower sides of the Instron were fabricated for the evaluation. The mean maximum pull‐out strength for fixation using 3.5‐mm diameter screws was 241.9 ± 67.8 N, whereas the mean pull‐out strength in fixation with 2.7‐mm diameter screws was 228.1 ± 63.0 N. There was no statistically significant difference between the two groups. Distal fragment fixation with distal clavicle locking plates using two 2.7‐mm diameter screws showed comparable biomechanical pull‐out strength at the time‐zero setting to fixations with a hook plate using two 3.5‐mm diameter screws. Therefore, the fixation of the distal fragment with a low‐profile plate and 2.7‐mm screws may be preferred as an alternative option if the distal fragment of the fractured clavicle is not extremely small.
No effects of early functional mobilization on gait patterns after acute Achilles tendon rupture repair
Authors: Aufwerber Susanna , Naili Josefine E. , Grävare Silbernagel Karin , Ackermann Paul W. 
Published: October 2021

AbstractThis study aimed to compare recovery of gait patterns in patients treated with early functional mobilization (EFM) or standard treatment (ST) after Achilles tendon rupture repair. Second, this study aimed to explore associations between gait patterns and tendon elongation and calf muscle atrophy, respectively. Forty‐seven patients (12 females), mean age 38.7 (7.3) years, were included. Patients were postoperatively randomized to EFM (n = 29), including immediate weightbearing and ankle motion for 6 weeks, or ST (n = 18), with 2 weeks of unloading in a plaster cast followed by 4 weeks of weightbearing in an orthosis. Three‐dimensional gait analyses were performed at 8 weeks and 6 months postoperatively to evaluate ankle and knee kinematics and kinetics. Ultrasound imaging was performed to assess tendon length and calf muscle atrophy. At 8 weeks, there were no significant group differences in ankle and knee kinematics and kinetics, while side‐to‐side differences between injured and uninjured side were present within both groups. At 6 months, the ST group exhibited higher generating ankle power and greater peak moments in ankle and knee compared to the EFM group. In both groups, peak ankle dorsiflexion angle was greater on the injured side compared to the uninjured side. No correlations were found between ankle joint gait deviations and degree of tendon elongation or muscle atrophy. Clinical significance: The accelerated rehabilitation regimen with EFM did not result in a more symmetrical gait pattern. The gait pattern deviations in the ankle joint were not related to the degree of muscle atrophy or tendon elongation.