Miracle-dz/UniFAR-FTUs huggingface dataset:
Adaptive immunity in the joint of rheumatoid arthritis

Abstract Adaptive immunity plays central roles in the pathogenesis of rheumatoid arthritis (RA), as it is regarded as an autoimmune disease. Clinical investigations revealed infiltrations of B cells in the synovium, especially those with ectopic lymphoid neogenesis, associate with disease severity. While some B cells in the synovium differentiate into plasma cells producing autoantibodies such as anti-citrullinated protein antibody, others differentiate into effector B cells producing proinflammatory cytokines and expressing RANKL. Synovial B cells might also be important as antigen-presenting cells. Synovial T cells are implicated in the induction of antibody production as well as local inflammation. In the former, a recently identified CD4 T cell subset, peripheral helper T (Tph), which is characterized by the expression of PD-1 and production of CXCL13 and IL-21, is implicated, while the latter might be mediated by Th1-like CD4 T cell subsets that can produce multiple proinflammatory cytokines, including IFN-γ, TNF-α, and GM-CSF, and express cytotoxic molecules, such as perforin, granzymes and granulysin. CD8 T cells in the synovium are able to produce large amount of IFN-γ. However, the involvement of those lymphocytes in the pathogenesis of RA still awaits verification. Their antigen-specificity also needs to be clarified.
Frameworks for trainee education in the nonoperating room setting

Purpose of review As the volume and types of procedures requiring anesthesiologist involvement in the nonoperating room anesthesia (NORA) setting continue to grow, it is important to create a formal curriculum and clearly define educational goals. Recent findings A NORA rotation should be accompanied by a dedicated curriculum that should include topics such as education objectives, information about different interventional procedures, anesthesia techniques and equipment, and safety principles. NORA environment may be unfamiliar to anesthesia residents. The trainees must also learn the principles of efficiency, rapid recovery from anesthesia, and timely room turnover. Resident education in NORA should be an essential component of their training. The goals and objectives of the NORA educational experience should include not only developing the clinical knowledge necessary to implement the specific type of anesthetic desired for each procedure, but also the practical knowledge of care coordination needed to safely and efficiently work in the NORA setting. Summary As educators, we must foster and grow a resident's resilience by continually challenging them with new clinical scenarios and giving them appropriate autonomy to take risks and move outside of their comfort zone. Residents should understand that exposure to such unique and demanding environment can be transformative.
Evaluation of doxorubicin-induced early multi-organ toxicity in male CD1 mice by biodistribution of 18F-FDG and 67Ga-citrate. Pilot study

Abstract The search for methods that identify early toxicity, induced by chemotherapy, is urgent. Changes in the biodistribution of radiopharmaceuticals could give information on early toxicity. Ten-week-old CD1 male mice were divided into four groups. Two groups were administered a weekly dose of 5 mg/kg of doxorubicin hydrochloride (DOX) for 5 weeks and the control groups were administered saline solution. One week after the end of treatment, the biodistribution of 18F-FDG and 67Ga-citrate were carried out, as was the quantification of plasma enzymes CK, CK-MB, LDH and AST. All enzymes were higher in the treated animals, but only significant (p < 0.05) in the case of CK-MB. 18F-FDG uptake increased in all organs of treated animals except retroperitoneal fat, being significant in spleen, brain, heart, liver, lung, kidney, and inguinal fat. 67Ga-citrate had a more complex pattern. The uptake in the DOX group was higher in spleen, lung, kidney, testes, and gonadal fat, it did not change in brain, heart, and liver, and it was lower in the rest of the organs. It only showed significant differences in lung and pancreas. A thorough discussion of the possible causes that produced the change in biodistributions of both radiopharmaceuticals is included. The pilot study showed that both radiopharmaceuticals could identify early multi-organ toxicity induced by DOX. Although 18F-FDG seems to be better, 67Ga-citrato should not be ruled out a priori. The detection of early toxicity would serve to adopt treatments that prevent its progression, thus improving patient’s quality of life.
Fully convolutional network-based multi-output model for automatic segmentation of organs at risk in thorax

Purpose: To propose a multi-output fully convolutional network (MOFCN) to segment bilateral lung, heart and spinal cord in the planning thoracic computed tomography (CT) slices automatically and simultaneously. Methods: The MOFCN includes two components: one main backbone and three branches. The main backbone extracts the features about lung, heart and spinal cord. The extracted features are transferred to three branches which correspond to three organs respectively. The longest branch to segment spinal cord is nine layers, including input and output layers. The MOFCN was evaluated on 19,277 CT slices from 966 patients with cancer in the thorax. In these slices, the organs at risk (OARs) were delineated and validated by experienced radiation oncologists, and served as ground truth for training and evaluation. The data from 61 randomly chosen patients were used for training and validation. The remaining 905 patients’ slices were used for testing. The metric used to evaluate the similarity between the auto-segmented organs and their ground truth was Dice. Besides, we compared the MOFCN with other published models. To assess the distinct output design and the impact of layer number and dilated convolution, we compared MOFCN with a multi-label learning model and its variants. By analyzing the not good performances, we suggested possible solutions. Results: MOFCN achieved Dice of 0.95 ± 0.02 for lung, 0.91 ± 0.03 for heart and 0.87 ± 0.06 for spinal cord. Compared to other models, MOFCN could achieve a comparable accuracy with the least time cost. Conclusion: The results demonstrated the MOFCN’s effectiveness. It uses less parameters to delineate three OARs simultaneously and automatically, and thus shows a relatively low requirement for hardware and has potential for broad application.
Validation and update of the Lémann index to measure cumulative structural bowel damage in Crohn's disease.

BACKGROUND The Lémann index is a tool measuring cumulative structural bowel damage in Crohn's disease (CD). We here report its validation and updating. METHODS This was an international, multicenter, prospective, cross-sectional observational study. At each center, 10 inclusions, stratified by CD duration and location, were planned. For each patient, the digestive tract was divided into 4 organs, upper tract, small bowel, colon/rectum, anus, and subsequently into segments, explored systematically by magnetic resonance imaging (MRI), and by endoscopies in relation to disease location. For each segment, investigators retrieved information on previous surgical procedures, identified predefined strictures and penetrating lesions of maximal severity (grades 1-3) at each organ investigational method (gastroenterologist and radiologist for MRI), provided segmental damage evaluation ranging from 0.0 to 10.0 (complete resection). Organ resection-free cumulative damage evaluation was then calculated from the sum of segmental damages. Then, investigators provided a 0-10 global damage evaluation from the 4 organ standardized cumulative damage evaluations. Simple linear regressions of investigator damage evaluations on their corresponding Lémann index were studied, as well as calibration plots. Finally, updated Lémann index was derived through multiple linear mixed models applied to combined development and validation samples. RESULTS In 15 centers, 134 patients were included. Correlation coefficients between investigator damage evaluations and Lémann indexes were above 0.80. When analyzing data in 272 patients from both samples and 27 centers, the unbiased correlation estimates were 0.89, 0,97, 0,94, 0.81, 0.91 for the 4 organs and globally, and stable when applied to one sample or the other. CONCLUSIONS The updated Lémann index is a well-established index to assess cumulative bowel damage in Crohn's disease that can be used in epidemiological studies and disease modification trials.
Is addition or removal of seminal plasma able to compensate for the dilution effect of buffalo semen?

The present study aimed to compensate dilution effect using additional seminal plasma (SP) in conventional (80 million (M) spermatozoa/ml) dose and low spermatozoa/dose (8M spermatozoa/ml). We also attempted to confirm whether removal of SP before the extension of ejaculates affects post‐thaw sperm quality of buffalo semen. For this, semen ejaculates (N = 15) were divided into four groups: control (CON), removal of SP by centrifugation (NSP), resuspension of the centrifuged semen pellet into SP (CEN) and extra supplementation of SP (ESP). All groups were diluted into two different semen doses to 20 and 2M spermatozoa/0.25 ml using tris egg yolk extender and subsequently cryopreserved. We found that neither addition nor removal of SP affected sperm motility, kinematics, longevity, mitochondrial superoxide production and high mitochondrial membrane potential (MMP). Further, the addition or removal of SP was not able to compensate dilution effect in 2M groups resulting in a significantly (p < .05) reduction in sperm motility, kinematics, sperm longevity, membrane integrity, MMP, and an increase production of mitochondrial superoxide. In conclusion, it appears that role of SP in the sperm cryopreservation process is insignificant.
Auxin fluxes through plasmodesmata.

Characterising the processes that control auxin dynamics is essential to understanding how auxin regulates plant development. Over recent years, several studies have investigated auxin diffusion through plasmodesmata, characterising this cell-to-cell diffusion and demonstrating that it affects auxin distributions. Furthermore, studies have shown that plasmodesmatal auxin diffusion affects developmental processes, including phototropism, lateral root emergence and leaf hyponasty. This short Tansley insight review describes how these studies have contributed to our understanding of auxin dynamics and discusses potential future directions in this area.
Genetic mapping of highly versatile and solvent-tolerant Pseudomonas putida B6-2 (ATCC BAA-2545) as a 'superstar' for mineralization of PAHs and dioxin-like compounds.

Polycyclic aromatic hydrocarbons (PAHs) and dioxin-like compounds, including sulfur, nitrogen and oxygen heterocycles, are widespread and toxic environmental pollutants. A wide variety of microorganisms capable of growing with aromatic polycyclic compounds are essential for bioremediation of the contaminated sites and the Earth's carbon cycle. Here, cells of Pseudomonas putida B6-2 (ATCC BAA-2545) grown in the presence of biphenyl (BP) are able to simultaneously degrade PAHs and their derivatives, even when they are present as mixtures, and tolerate high concentrations of extremely toxic solvents. Genetic analysis of the 6.37 Mb genome of strain B6-2 reveals coexistence of gene clusters responsible for central catabolic systems of aromatic compounds and for solvent tolerance. We used functional transcriptomics and proteomics to identify the candidate genes associated with catabolism of BP and a mixture of BP, dibenzofuran, dibenzothiophene and carbazole. Moreover, we observed dynamic changes in transcriptional levels with BP, including in metabolic pathways of aromatic compounds, chemotaxis, efflux pumps, and transporters potentially involved in adaptation to PAHs. This study on the highly versatile activities of strain B6-2 suggests it to be a potentially useful model for bioremediation of polluted sites and for investigation of biochemical, genetic and evolutionary aspects of Pseudomonas. This article is protected by copyright. All rights reserved.
Mesoporous and Graphitic Carbide-Derived Carbons as Selective and Stable Catalysts for the Dehydrogenation Reaction

Dehydrogenation of ethylbenzene to styrene is one of the most important catalytic processes in chemical industry. While it was demonstrated that nanocarbons like nanotubes, nanodiamond, or nanographite show high performance, especially selectivity, these powders give rise to handling problems, high pressure drop, hampered heat and mass transfer, and unclear health risks. More common macroscopic carbon materials like activated carbons show unsatisfying selectivity below 80%. In this study, mesoporous, graphitic, and easy to handle carbon powders were synthesized on the basis of the reactive extraction of titanium carbide in a novel temperature regime. This resulted in extraordinary properties like a mean pore diameter of up to 8 nm, pore volumes of up to 0.90 mL g–1, and graphite crystallite sizes exceeding 25 nm. Exceptional styrene selectivities of up to 95% were observed for materials synthesized above 1300 °C and pretreated with nitric acid. Furthermore, the long-term stability of these non-nanocarbon .
Differences Between Older Adults Who Do and Do Not Try Hearing Aids and Between Those Who Keep and Return the Devices

The focus of this study was on the differences between older adults who complied with a clinical recommendation for hearing-aid acquisition (adherents; N = 105) and those who did not (nonadherents; N = 34) among a group of research volunteers from the community. All participants were first-time hearing-aid users. Differences between adherents and nonadherents were examined across several domains, including demographic variables, audiometric measures, measures of affect and personality, cognitive variables, hearing-aid expectations, and the perceived hearing difficulties of the older adults and their adjustments to those difficulties. It was found that the adherents differed significantly (p < .05) from the nonadherents primarily in their perceived difficulties and reactions to them as well as their expectations for hearing aids. Importantly, the pattern of differences between the adherents and nonadherents was primarily confined to measures that could potentially be shaped by appropriate counseling and education of the older adult. In a secondary analysis, among the 105 adherents, a small group (N = 21) returned their hearing aids for credit with 15 of them completing the outcome measures at the end of a 1-month trial period. When comparisons were made between the adherents who kept their hearing aids (N = 84) and those who returned them, the primary differences between these two groups of adherents were in the poorer aided outcomes obtained by those who returned their devices.
Dual-task walking and automaticity after Stroke: Insights from a secondary analysis and imaging sub-study of a randomised controlled trial

Objective: To test the extent to which initial walking speed influences dual-task performance after walking intervention, hypothesising that slow walking speed affects automatic gait control, limiting executive resource availability. Design: A secondary analysis of a trial of dual-task (DT) and single-task (ST) walking interventions comparing those with good (walking speed ⩾0.8 m s−1, n = 21) and limited (walking speed <0.79 m s−1, n = 24) capacity at baseline. Setting: Community. Subjects: Adults six-months post stroke with walking impairment. Interventions: Twenty sessions of 30 minutes treadmill walking over 10 weeks with (DT) or without (ST) cognitive distraction. Good and limited groups were formed regardless of intervention received. Main measures: A two-minute walk with (DT) and without (ST) a cognitive distraction assessed walking. fNIRS measured prefrontal cortex activation during treadmill walking with (DT) and without (ST) Stroop and planning tasks and an fMRI sub-study used ankle-dorsiflexion to simulate walking. Results: ST walking improved in both groups (∆baseline: Good = 8.9 ± 13.4 m, limited = 5.3±8.9 m, Group × time = P < 0.151) but only the good walkers improved DT walking (∆baseline: Good = 10.4 ± 13.9 m, limited = 1.3 ± 7.7 m, Group × time = P < 0.025). fNIRS indicated increased ispilesional prefrontal cortex activation during DT walking following intervention (P = 0.021). fMRI revealed greater DT cost activation for limited walkers, and increased resting state connectivity of contralesional M1 with cortical areas associated with conscious gait control at baseline. After the intervention, resting state connectivity between ipsilesional M1 and bilateral superior parietal lobe, involved in integrating sensory and motor signals, increased in the good walkers compared with limited walkers. Conclusion: In individual who walk slowly it may be difficult to improve dual-task walking ability. Registration: ISRCTN50586966
Endovascular treatment of calcific lesions of the common femoral artery using atherectomy device associated with scoring balloon angioplasty in diabetic patients with high “major amputation” risk

Objectives To investigate the outcomes of patients with calcific lesions in the common femoral artery undergoing endovascular procedures with atherectomy device and scoring balloon angioplasty combined with treatment of steno-occlusive disease of the remaining arterial districts of the lower limb. Methods Between January 2015 and December 2018, 11 diabetic patients at high risk for “major amputation”, with calcific lesions of the common femoral artery and ischemic ulcers requiring endovascular treatment were retrospectively evaluated. Technical success was defined as revascularization of the common femoral artery with a residual stenosis lower than 30%. Primary endpoints were an immediate increase of perilesional transcutaneous oxygen pressure (TCPO2) > 40 mmHg, ulcerative lesions improvement up to healing or skin flaps re-epithelialization after minor amputation, limb rescue with rejected major amputation, and resolution of rest pain if present. Results The success rate of the revascularization procedures was 100%. No patient underwent surgical conversion. One case of peri-operative bleeding at the brachial access site was observed. There were no cases of arterial dissection or undesired distal embolization. The average baseline value of perilesional TCPO2 was 21.8 ± 9.2 mmHg. The mean TCPO2 value was 57.4 ± 7.2 mmHg three days after the procedure (P < 0.05), and 51.2 ± 9.8 mmHg 15 days after (P < 0.05). Minor amputations were performed in five patients with advanced ulcerative lesions. No major amputations were performed in the follow-up period. At 14 months follow-up, one patient developed new occlusion of the CFA for extension from the external iliac artery and underwent a new endovascular procedure. We observed an overall primary patency rate of 91% and a primary assisted patency rate of 100% in our 18-month follow-up. Conclusions Endovascular approach for severely calcified atherosclerotic lesions of the common femoral artery seems to represent a valid therapeutic option associated with promising results in terms of clinical outcome and low complication rates.
Psychopathy Profiles and Personality Assessment Inventory Scores in a Sex Offender Risk Assessment Field Setting

A growing body of research suggests there are identifiable psychopathy subtypes among offenders scored on Hare’s Psychopathy Checklist–Revised (PCL-R; Hare, 2003). We used latent profile analysis to examine the generalizability of these subtype findings to PCL-R scores (N = 615) assigned in a sex offender risk assessment field setting and to examine how offender subtypes differ on measures of comorbid psychopathology, risk, and treatment amenability from the Personality Assessment Inventory. Consistent with prior research, we identified four subtypes when using PCL-R scores from all offenders: Prototypic psychopathy (n = 239, 38.9%), callous-conning (n = 154, 25.0%), sociopathic (n = 96, 15.6%), and general offenders (n = 126, 20.5%). Prototypic and sociopathic subtypes exhibited the highest levels of comorbid psychopathology and risk for potential violence. We identified classes consistent with primary (n = 66, 36.7%) and secondary (n = 114, 63.3%) psychopathy among offenders with PCL-R total scores ≥ 25, and found higher levels of comorbid psychopathology and potential for violence among those in the secondary psychopathy class. Findings provide support the generalizability of existing PCL-R subtype findings to field scores and show how those with similar PCL-R total scores may differ on scores from commonly used multiscale inventories.
Depletion of the gut microbiota differentially affects the impact of whey protein on high‐fat diet‐induced obesity and intestinal permeability

Whey protein isolate (WPI) is considered a dietary solution to obesity. However, the exact mechanism of WPI action is still poorly understood but is probably connected to its beneficial effect on energy balance, adiposity, and metabolism. More recently its ability to modulate the gut microbiota has received increasing attention. Here, we used a microbiota depletion, by antibiotic cocktail (ABX) administration, to investigate if the gut microbiota mediates the physiological and metabolic changes observed during high‐fat diet (HFD)‐WPI consumption. C57BL/6J mice received a HFD containing WPI (HFD‐WPI) or the control non‐whey milk protein casein (HFD‐CAS) for 5 or 10 weeks. HFD‐fed mice supplemented with WPI showed reduced body weight gain, adiposity, Ob gene expression level in the epidydimal adipose tissue (eWAT) and plasma leptin relative to HFD‐CAS‐fed mice, after 5‐ or 10‐weeks intervention both with or without ABX treatment. Following 10‐weeks intervention, ABX and WPI had an additive effect in lowering adiposity and leptin availability. HFD‐WPI‐fed mice showed a decrease in the expression of genes encoding pro‐inflammatory markers (MCP‐1, TNFα and CD68) within the ileum and eWAT, compared to HFD‐CAS‐fed mice, without showing alterations following microbiota depletion. Additionally, WPI supplementation decreased HFD‐induced intestinal permeability disruption in the distal ileum; an effect that was reversed by chronic ABX treatment. In summary, WPI reverses the effects of HFD on metabolic and physiological functions through mainly microbiota‐independent mechanisms. Moreover, we demonstrate a protective effect of WPI on HFD‐induced inflammation and ileal permeability disruption, with the latter being reversed by gut microbiota depletion.
New insights in statins affecting atheromatous plaque macrophages

Purpose of review Macrophages are key protagonists of atherosclerotic plaque development and hence represent targets of therapeutic intervention. Statins are the most potent widely used atheroprotective drugs. Therefore, whether and how statins influence atheromatous plaque macrophages has remained at the center of cardiovascular research for decades. Recent findings Because statins are capable of regulating macrophage functions in cell culture, largely independent of their cholesterol-lowering effect, it was assumed that these pleiotropic effects operate in vivo as well. Recent experimental data, in line with clinical observations, indicate, however, that statins do not interact with macrophages in atherosclerotic plaques, directly, and instead control their functions and assembly indirectly via changes to circulating lipid levels and endothelial activation. Summary Statin-mediated lipid lowering induces plaque regression which is characterized by a decline in plaque macrophage content. Understanding how statins provoke this protective phenotype may inspire conceptually new therapeutic approaches in cardiovascular medicine.