Miracle-dz/UniFAR-FTUs huggingface dataset:
Inducing Transient Mixed Chimerism for Allograft Survival Without Maintenance Immunosuppression With Combined Kidney and Bone Marrow Transplantation: Protocol Optimization

Supplemental Digital Content is available in the text. Background. Tolerance induction is an important goal in the field of organ transplantation. We have sequentially modified our conditioning regimen for induction of donor-specific tolerance in recipients of major histocompatibility complex-mismatched combined kidney and bone marrow transplantation (CKBMT). Methods. From December 2011 to May 2017, 8 major histocompatibility complex-mismatched patients received CKBMT. The initial conditioning regimen (protocol 1) consisted of cyclophosphamide (CP), rituximab, rabbit antithymocyte globulin, and thymic irradiation. Tacrolimus and steroids were used for the maintenance of immunosuppression (IS). Results. This regimen was complicated by transient acute kidney injury, which has been the major clinical feature of engraftment syndrome and side effects of CP, although one of 2 subjects successfully discontinued his IS for 14 months. The conditioning regimen was modified by reducing the CP dose and adding fludarabine (protocol 2). The final modification was reducing the fludarabine and rabbit antithymocyte globulin doses (protocol 3). Mixed chimerism, detected by the short tandem repeat method, was achieved transiently in all subjects for 3–20 weeks. Among the 3 subjects treated with protocol 2, IS was successfully discontinued for >35 months in one subject, but the other 2 subjects suffered from severe BK virus-associated nephritis. All 3 subjects treated with protocol 3 tolerated the protocol well and have successfully discontinued IS for >4–41 months. Interestingly, de novo donor-specific antibody was not detected in any subject during all the follow-up periods. Conclusions. Our clinical trial has shown that long-term renal allograft survival without maintenance IS can be achieved by induction of mixed chimerism following CKBMT.
Return to Play and Long-term Participation in Pivoting Sports After Anterior Cruciate Ligament Reconstruction

Background: Rupture of the anterior cruciate ligament (ACL) is a common and feared injury among athletes because of its potential effect on further sports participation. Reported rates of return to pivoting sports after ACL reconstruction (ACLR) vary in the literature, and the long-term consequences of returning have rarely been studied. Purpose: To examine the rate and level of return to pivoting sports after ACLR, the duration of sports participation, and long-term consequences of returning to pivoting sports. Study Design: Cohort study; Level of evidence, 2. Methods: All primary ACLRs with a bone–patellar tendon–bone autograft between 1987 and 1994 (N = 234) in athletes participating in team handball, basketball, or soccer before injury were selected from a single-center quality database. A long-term evaluation (median, 25 years; range, 22-30 years) was performed using a questionnaire focusing on return to pivoting sports, the duration of sports activity after surgery, later contralateral ACL injuries, revision surgery, and knee replacement surgery. Participants were stratified into 2 groups depending on the time between injury and surgery (early, <24 months; late, ≥24 months). Results: A total of 93% of patients (n = 217) responded to the questionnaire. Although 83% of patients returned to pivoting sports after early ACLR, only 53% returned to preinjury level. Similar return-to-sport rates were observed in males and females (P > .05), but males had longer sports careers (median, 10 years; range, 1-23 years) than females (median, 4 years; range, 1-25 years; P < .001). The incidence of contralateral ACL injuries was 28% among athletes who returned to sports versus 4% among athletes who did not return (P = .017) after early ACLR. The pooled reinjury rate after return to preinjury level of sports was 41% (30%, contralateral injuries; 11%, revision surgery). The incidence of contralateral ACL injuries was 32% among females versus 23% among males (P > .05) and, for revision surgery, was 12% among females versus 7% among males (P > .05) after returning to sports. Having a late ACLR was associated with an increased risk of knee replacement surgery (9% vs 3%; P = .049) when compared with having an early ACLR. Conclusion: ACLR does not necessarily enable a return to preinjury sports participation. By returning to pivoting sports after ACLR, athletes are also facing a high risk of contralateral ACL injuries. Long-term evaluations in risk assessments after ACLR are important, as a significant number of subsequent ACL injuries occur later than the routine follow-up.
Expert-level detection of acute intracranial hemorrhage on head computed tomography using deep learning

Significance Computed tomography (CT) of the head is the workhorse medical imaging modality used worldwide to diagnose neurologic emergencies. However, these gray scale images are limited by low signal-to-noise, poor contrast, and a high incidence of image artifacts. A unique challenge is to identify tiny subtle abnormalities in a large 3D volume with near-perfect sensitivity. We used a single-stage, end-to-end, fully convolutional neural network to achieve accuracy levels comparable to that of highly trained radiologists, including both identification and localization of abnormalities that are missed by radiologists. Computed tomography (CT) of the head is used worldwide to diagnose neurologic emergencies. However, expertise is required to interpret these scans, and even highly trained experts may miss subtle life-threatening findings. For head CT, a unique challenge is to identify, with perfect or near-perfect sensitivity and very high specificity, often small subtle abnormalities on a multislice cross-sectional (three-dimensional [3D]) imaging modality that is characterized by poor soft tissue contrast, low signal-to-noise using current low radiation-dose protocols, and a high incidence of artifacts. We trained a fully convolutional neural network with 4,396 head CT scans performed at the University of California at San Francisco and affiliated hospitals and compared the algorithm’s performance to that of 4 American Board of Radiology (ABR) certified radiologists on an independent test set of 200 randomly selected head CT scans. Our algorithm demonstrated the highest accuracy to date for this clinical application, with a receiver operating characteristic (ROC) area under the curve (AUC) of 0.991 ± 0.006 for identification of examinations positive for acute intracranial hemorrhage, and also exceeded the performance of 2 of 4 radiologists. We demonstrate an end-to-end network that performs joint classification and segmentation with examination-level classification comparable to experts, in addition to robust localization of abnormalities, including some that are missed by radiologists, both of which are critically important elements for this application.
Putting life on hold: lived experiences of people with obesity.

Obesity presents challenges in everyday life, one of which involves the existential aspects of living life as a person with obesity. There is a need for understanding the existential experiences, but there is limited in-depth research about these experiences of people with obesity. The aim of this study was to gain deeper insight into the existential experiences of people dealing with obesity. We performed a qualitative study that included in-depth interviews with seven men and 14 women with obesity (body mass index ≥ 35 kg/m2 ) aged 18-59 years. The study took a phenomenological-hermeneutic approach in which the participants' own experiences formed the basis for understanding their lifeworld. The lived experiences of people dealing with obesity were characterised by several existential challenges. One overarching theme-Putting life on hold when struggling with obesity-was developed based on three themes: The body as an impediment to living the desired life, to being oneself and to moving on in life. These findings illustrate the complex existential experience of life, body and existence faced by people dealing with obesity. Based on these findings, we discuss whether people with obesity who experience 'putting life on hold' are attuned to live their life to the fullest in some areas. Their embodied experiences seem to challenge them to experience the joy of life, to appear as a whole self and to live life in the moment. Reflecting on obesity in the context of life and life phenomena seems to provide deeper insights into the existence of people living with obesity and may help to advance a more comprehensive approach in obesity health care.
Ustekinumab treatment for hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a follicular occlusive inflammatory skin disease that occurs in the axilla, groin, buttocks and vulval region. Control of the intractable inflammation is a primary goal of HS treatments. Benefit of anti‐tumor necrosis factor (TNF) antibodies against HS have been reported, and adalimumab has been approved for HS in Europe, the USA and Japan. However, the alternative therapies for anti‐TNF antibodies have not been established yet. We experienced a case of HS which developed during the infliximab treatment for Crohn’s disease (CD) and was well managed by ustekinumab (UST). We reviewed the articles relating to ustekinumab treatments for HS. Twenty‐four HS patients, 16 women and eight men, have been treated with ustekinumab. The average age was 35.7 ± 10.8 years (mean ± SD). All were of Hurley stage II or III. Ten (10/24, 41.6%) had received anti‐TNF drugs including infliximab, adalimumab and etanercept prior to UST treatment for HS. Although the initial doses varied from 45 mg s.c. to 390 mg i.v. , all cases were treated with 45 or 90 mg s.c. every 8 or 12 weeks at the regular dose, by following the regimen for psoriasis or CD. HS in most of the cases started to improve after 3–5 months of UST initiation, and some achieved complete remission. To our knowledge, our case is the first Asian HS patient improved by UST. Overall, UST is useful for HS and could be an alternative treatment if HS patients do not respond to other medications including anti‐TNF drugs.
Revisiting a Previously Validated Temperament Test in Shelter Dogs, Including an Examination of the Use of Fake Model Dogs to Assess Conspecific Sociability

Simple Summary Globally, many unwanted dogs enter rescue shelters. Shelter staff often avail of behavioural tests as an early screening tool to identify areas of concern to minimise the welfare risk associated with long-term kennelling and failed adoptions. A number of requirements need to be verified in order for a test to become a useful assessment tool, including how reliable and accurate the measurements are. For these tools to be widely used, they need to be feasible and reproducible. We refined a previously validated temperament test for shelter dogs’ assessment, developed in Italy, and applied it to two populations of shelter dogs in the UK. The test measured dog behaviour in the kennel, sociability towards people and other dogs, docility to leash, playfulness, cognitive skills, and reactivity. The test proved easy to replicate, with key outcomes that are consistent with existing research on this topic. Furthermore, an additional experiment provided support for the use of fake dogs instead of real ones to assess sociability to dogs. However, we also highlight the importance of interpreting these data with caution, and advocate the use of behavioural tests as a partial screening tool to be used in conjunction with more extensive behavioural and welfare monitoring. Abstract This study assessed the feasibility and reproducibility of a previously validated temperament test (TT) for shelter dogs. The test was developed to measure dog behaviour in the kennel, and traits of sociability towards people and other dogs, docility to leash, playfulness, cognitive skills, and reactivity. We introduced the use of differently sized fake dogs to check their appropriateness in correctly assessing sociability to dogs to broaden its applicability (as the original study used real stimulus dogs). We hypothesised that dogs’ responses may be modulated by the body size of the stimulus dog presented. The reduction analysis of the TT scores extracted five main dimensions (explaining 70.8% of variance), with high internal consistency (alpha > 0.65) and being broadly consistent with existing research. Behavioural components that were extracted from the fake dog experiment showed that dogs are likely to show signs of anxiety and fear toward both the real and fake dog. Dogs’ responses towards a real vs. fake stimulus were significantly correlated (p < 0.05) and they were not affected by the size of the stimulus (p > 0.05). We discuss the importance of interpreting these data with caution and use behavioural tests as a partial screening tool to be used in conjunction with more extensive behavioural and welfare monitoring.
Cyst Reduction in a Polycystic Kidney Disease Drosophila Model Using Smac Mimics

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited malady affecting 12.5 million people worldwide. Therapeutic options to treat PKD are limited, due in part to lack of precise knowledge of underlying pathological mechanisms. Mimics of the second mitochondria-derived activator of caspases (Smac) have exhibited activity as antineoplastic agents and reported recently to ameliorate cysts in a murine ADPKD model, possibly by differentially targeting cystic cells and sparing the surrounding tissue. A first-in-kind Drosophila PKD model has now been employed to probe further the activity of novel Smac mimics. Substantial reduction of cystic defects was observed in the Malpighian (renal) tubules of treated flies, underscoring mechanistic conservation of the cystic pathways and potential for efficient testing of drug prototypes in this PKD model. Moreover, the observed differential rescue of the anterior and posterior tubules overall, and within their physiologically diverse intermediate and terminal regions implied a nuanced response in distinct tubular regions contingent upon the structure of the Smac mimic. Knowledge gained from studying Smac mimics reveals the capacity for the Drosophila model to precisely probe PKD pharmacology highlighting the value for such critical evaluation of factors implicated in renal function and pathology.
Low Cost Gaze Estimation: Knowledge-Based Solutions

Eye tracking technology in low resolution scenarios is not a completely solved issue to date. The possibility of using eye tracking in a mobile gadget is a challenging objective that would permit to spread this technology to non-explored fields. In this paper, a knowledge based approach is presented to solve gaze estimation in low resolution settings. The understanding of the high resolution paradigm permits to propose alternative models to solve gaze estimation. In this manner, three models are presented: a geometrical model, an interpolation model and a compound model, as solutions for gaze estimation for remote low resolution systems. Since this work considers head position essential to improve gaze accuracy, a method for head pose estimation is also proposed. The methods are validated in an optimal framework, I2Head database, which combines head and gaze data. The experimental validation of the models demonstrates their sensitivity to image processing inaccuracies, critical in the case of the geometrical model. Static and extreme movement scenarios are analyzed showing the higher robustness of compound and geometrical models in the presence of user’s displacement. Accuracy values of about 3° have been obtained, increasing to values close to 5° in extreme displacement settings, results fully comparable with the state-of-the-art.
Adipose-Derived Stem Cell Transplantation Inhibits Vascular Inflammatory Responses and Endothelial Dysfunction in Rats with Atherosclerosis

Purpose This study aimed to investigate the effect of adipose-derived stem cell (ADSC) transplantation on atherosclerosis (AS) and its underlying mechanisms. Materials and Methods In our study, rat AS model was established, and ADSCs were isolated and cultured. Atherosclerotic plaque and pathological symptoms of thoracic aorta were measured by Oil Red O staining and Hematoxylin-Eosin staining, respectively. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured by an automatic biochemical analyzer. Expressions of vascular endothelial growth factor (VEGF), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), aortic endothelin-1 (ET-1), interleukin-6 (IL-6), c-reactive protein (CRP), and tumor necrosis factor α (TNF-α) were measured by enzyme linked immunosorbent assay, VEGF, VCAM-1, ICAM-1, ET-1, respectively, and NF-κB p65 mRNA expressions were detected by quantitative real-time polymerase chain reaction. Protein expressions of VEGF, VCAM-1, ICAM-1, ET-1, NF-κB p65, p-NF-κB p65, and IκBα were measured by western blot. Moreover, NF-κB p65 expression was measured by immunofluorescence staining. Results ADSC transplantation alleviated the pathological symptoms of aortic AS. ADSC transplantation decreased the levels of TC, TG, and LDL-C and increased serum HDL-C level. Meanwhile, ADSC transplantation decreased the levels of IL-6, CRP, and TNF-α in AS rats. Moreover, the expressions of VEGF, ET-1, VCAM-1, and ICAM-1 were decreased by ADSC transplantation. ADSC transplantation inhibited phosphorylation of NF-κB p65 and promoted IκBα expression in AS rats. Conclusion Our study demonstrated that ADSC transplantation could inhibit vascular inflammatory responses and endothelial dysfunction by suppressing NF-κB pathway in AS rats.
The Prevalence and Nature of Service Academy Mentoring: A Study of Navy Midshipmen

Mentoring relationships (mentorships) are often considered essential for the effective career development of junior professionals in a range of fields. Although research on mentorships in the military indicates that mentoring correlates with both success and satisfaction, we know little about the mentorships of officers in training. In this study, 568 midshipmen at the United States Naval Academy (USNA) responded to a survey regarding their experience of having been mentored at USNA. Results indicated that 45% of midshipmen are mentored and that women are more likely to have a mentor (63%) than men (42%). Mentored midshipmen were significantly more satisfied with USNA, viewed mentorships as more important, and were more active mentors themselves. Salient mentor characteristics and functions were highly correlated with both personal and professional development. The authors discuss the implications of these findings and offer recommendations for extending this research.
Digital Image Correlation and Finite Element Analysis of Bone Strain Generated by Implant-Retained Cantilever Fixed Prosthesis.

PURPOSE The present study evaluated the displacement and strain generated in an implant- supported fixed prosthesis under axial and non-axial loads using two methods. MATERIALS AND METHODS Three implants were inserted in a resin block. The Digital Image Correlation (DIC) was used to measure displacement and strain generated on the surface of the resin blocks for the different load applications (500N, 1 image/second). A 3-dimensional model was constructed and a load of 500 N was applied at an axial point and a non-axial point through finite element analysis (FEA). RESULTS Both methods gave similar trends for the strains, and both gave slightly higher strains with non-axial loading. FEA predicted higher strain magnitude (±11%) in comparison with DIC, but with the same mechanical behavior. According to ANOVA, the loading influenced the strain concentration. Higher strain was generated for non-axial loading around the implant nearest to the loading. CONCLUSIONS For implant-retained cantilever fixed prosthesis, the same load applied in the lever arm induces higher strain in the cervical area of the last implant, which suggests more damaging potential than a load applied at the center of the prosthesis.
First quantification of the controlling role of humic substances in the transport of iron across the surface of the Arctic Ocean.

One of the main reasons behind our current lack of understanding of iron cycling in the oceans is our inability to characterize the ligands that control iron solubility, photosensitivity, reactivity and bioavailability. We currently lack consensus about the nature and origin of these ligands. Here, we present the first field application of a new methodological development that allows the selective quantification of the fraction of Fe complexed to humic substances (HS). In the HS-rich surface Arctic waters, including the Fe-rich TransPolar Drift (TPD), we found that HS iron binding groups were largely occupied by iron (49 %). The overall contribution of Fe-HS complexes to DFe concentrations was substantial at 80 % without significant differences between TPD and non-TPD waters. Stabilization and transport of large concentrations of DFe across the surface of the Arctic Ocean is due to the formation of high concentrations of Fe-HS complexes. Competition of Arctic Fe-HS complexes with desferrioxamine and EDTA indicated that their stability constants are considerably higher than the stability constants previously found for riverine HS in temperate estuaries and HS standard material. This is the first case of identification of the ligand dominating iron speciation over a specific region of the global ocean.
Guided Soft Attention Network for Classification of Breast Cancer Histopathology Images

An attention guided convolutional neural network (CNN) for the classification of breast cancer histopathology images is proposed. Neural networks are generally applied as black box models and often the network’s decisions are difficult to interpret. Making the decision process transparent, and hence reliable is important for a computer-assisted diagnosis (CAD) system. Moreover, it is crucial that the network’s decision be based on histopathological features that are in agreement with a human expert. To this end, we propose to use additional region-level supervision for the classification of breast cancer histopathology images using CNN, where the regions of interest (RoI) are localized and used to guide the attention of the classification network simultaneously. The proposed supervised attention mechanism specifically activates neurons in diagnostically relevant regions while suppressing activations in irrelevant and noisy areas. The class activation maps generated by the proposed method correlate well with the expectations of an expert pathologist. Moreover, the proposed method surpasses the state-of-the-art on the BACH microscopy test dataset (part A) with a significant margin.