Miracle-dz/UniFAR-FTUs huggingface dataset:
Does a Useful Test Exist to Properly Evaluate the Pathogenicity of Donor-specific Antibodies? Lessons From a Comprehensive Analysis in a Well-studied Single-center Kidney Transplant Cohort

Supplemental Digital Content is available in the text. Background. Donor-specific antibodies (DSA) play a major role in antibody-mediated rejection (AMR) and graft dysfunction. However, the clinical relevance of complement-binding anti-HLA antibodies remains unclear. Methods. Here, we analyzed DSA detected in the serum (sDSA) using single antigen bead, C1q, and C3d assays combined with the study of intragraft DSA (gDSA) in 86 patients who had DSA and underwent a kidney biopsy for cause (n = 58) or without evidence of kidney dysfunction (n = 28). DSA characteristics were collected and related to the presence of AMR, graft histological features, and allograft survival. Results. Forty-five patients (52%) had C1q+ DSA, and 42 (51%) had C3d+ DSA. Allograft biopsies revealed AMR in 63 cases (73%), regardless of kidney function. gDSA were identified in 74% of biopsies. We observed a strong correlation among single antigen bead mean fluorescence intensity and complement assays positivity, presence of gDSA, and AMR occurrence. Conclusions. Complement-binding DSA per se were not significantly associated with allograft survival in the entire study sample. Finally, gDSA predicted subsequent graft loss in patients who showed a stable renal function at the day of biopsy. Our data suggest that DSA mean fluorescence intensity and presence of gDSA might provide prognostic information during posttransplant monitoring.
FOLFOX treatment response prediction in metastatic or recurrent colorectal cancer patients via machine learning algorithms

Early identification of metastatic or recurrent colorectal cancer (CRC) patients who will be sensitive to FOLFOX (5‐FU, leucovorin and oxaliplatin) therapy is very important. We performed microarray meta‐analysis to identify differentially expressed genes (DEGs) between FOLFOX responders and nonresponders in metastatic or recurrent CRC patients, and found that the expression levels of WASHC4, HELZ, ERN1, RPS6KB1, and APPBP2 were downregulated, while the expression levels of IRF7, EML3, LYPLA2, DRAP1, RNH1, PKP3, TSPAN17, LSS, MLKL, PPP1R7, GCDH, C19ORF24, and CCDC124 were upregulated in FOLFOX responders compared with nonresponders. Subsequent functional annotation showed that DEGs were significantly enriched in autophagy, ErbB signaling pathway, mitophagy, endocytosis, FoxO signaling pathway, apoptosis, and antifolate resistance pathways. Based on those candidate genes, several machine learning algorithms were applied to the training set, then performances of models were assessed via the cross validation method. Candidate models with the best tuning parameters were applied to the test set and the final model showed satisfactory performance. In addition, we also reported that MLKL and CCDC124 gene expression were independent prognostic factors for metastatic CRC patients undergoing FOLFOX therapy.
Expression and localization of DAB1 and Reelin during normal human kidney development

Aim To explore the spatial and temporal expression patterns of DAB1 and Reelin in the developing and postnatal healthy human kidneys as potential determinants of kidney development. Methods Paraffin-embedded fetal kidney tissue between the 13/14th and 38th developmental weeks (dw) and postnatal tissue at 1.5 and 7 years were stained with DAB1 and Reelin antibodies by double immunofluorescence. Results During the fetal kidney development and postnatal period, DAB1 and Reelin showed specific spatial expression pattern and diverse fluorescence intensity. During the fetal period, DAB1 was strongly expressed in the distal convoluted tubules (DCT), with strong reactivity, and diversely in the proximal convoluted tubules (PCT) and glomeruli. In the postnatal period, DAB1 expression decreased. The strongest Reelin expression in early fetal stages was observed in the PCT. In the postnatal period, Reelin expression decreased dramatically in all observed structures. These two markers were colocalized during early developmental stages, mostly in PCT, DCT, and podocytes. Conclusion The appearance of DAB1 and Reelin during fetal kidney development confirms their potential significant role in the formation of kidney structure or function. High DAB1 expression in the DCT implies its regulatory role in tubular formation or function maintenance during development. Reelin was highly expressed in human kidneys at early fetal stages, mostly in the PCT, while at later fetal stages and postnatal period its expression decreased.
Quantification of Aortic Stiffness by Ultrasound Time-Harmonic Elastography: The Effect of Intravascular Pressure on Elasticity Measures in a Porcine Model.

OBJECTIVES The aim of this study was to investigate blood pressure dependency of ultrasound time-harmonic elastography (THE) for quantification of aortic stiffness. MATERIALS AND METHODS Thoracoabdominal aortas were surgically removed from 9 healthy domestic pigs and prepared for elastographic experiments. All vessels were connected to a saline-filled water column with adjustable height and pressurized over a range of 0 to 110 mm Hg in 10 mm Hg increments to simulate different levels of mean arterial pressure. In addition, 3 of the 9 aortas were soaked in 4% buffered formaldehyde for 60 minutes to simulate pathologic aortic stiffening. Ultrasound THE was performed in each vessel at each pressure level. For each pressure level, shear-wave speed (SWS) as a measure of aortic wall stiffness and luminal diameter were recorded. The pressure range between 30 and 110 mm Hg was used for statistical evaluation as it reflects a physiological mean arterial pressure range. Linear regression analysis and multivariate analysis with a general linear model were performed to evaluate the influence of increasing intravascular pressure and vessel diameter on measured SWS. RESULTS Median SWS in formalin-soaked aortas was significantly higher with 3.22 m/s (interquartile range [IQR], 0.01 m/s) versus 2.14 m/s (IQR, 0.09) at 30 mm Hg and 3.38 m/s (IQR, 0.01 m/s) versus 2.28 m/s (IQR, 0.07 m/s) at 110 mm Hg (each P = 0.01). Using linear regression analysis, an increase of aortic wall SWS of 0.017 m/s per 10 mm Hg intraluminal pressure was found in untreated aortas, whereas SWS increased by 0.020 m/s per 10 mm Hg in formalin-soaked aortas (both P = 0.001). The percentage of SWS caused by intraluminal pressure was 1.89% in formalin-soaked aortas and 2.50% in untreated aortas at 30 mm Hg and 6.61% for formalin-soaked aortas and 8.60% for untreated aortas at 110 mm Hg. Multivariate analysis showed no significant interaction of luminal diameter and measured SWS (P = 0.893). CONCLUSIONS In our model, aortic stiffness measurements by ultrasound time-harmonic elastography are influenced to a small extent by mean arterial pressure in a range of 1.89% to 8.60%. These findings emphasize the potential of ultrasound THE for measuring the intrinsic stiffness of the aortic wall in clinical routine.
2‐arachidonoylglycerol reduces chondroitin sulphate proteoglycan production by astrocytes and enhances oligodendrocyte differentiation under inhibitory conditions

The failure to remyelinate and regenerate is a critical impediment to recovery in multiple sclerosis (MS), resulting in severe dysfunction and disability. The chondroitin sulfate proteoglycans (CSPGs) that accumulate in MS lesions are thought to be linked to the failure to regenerate, impeding oligodendrocyte precursor cell (OPC) differentiation and neuronal growth. The potential of endocannabinoids to influence MS progression may reflect their capacity to enhance repair processes. Here, we investigated how 2‐arachidonoylglycerol (2‐AG) may affect the production of the CSPGs neurocan and brevican by astrocytes in culture. In addition, we studied whether 2‐AG promotes oligodendrocyte differentiation under inhibitory conditions in vitro. Following treatment with 2‐AG or by enhancing its endogenous tone through the use of inhibitors of its hydrolytic enzymes, CSPG production by rat and human TGF‐β1 stimulated astrocytes was reduced. These effects of 2‐AG might reflect its influence on TGF‐β1/SMAD pathway, signaling that is involved in CSPG upregulation. The matrix generated from 2‐AG‐treated astrocytes is less inhibitory to oligodendrocyte differentiation and significantly, 2‐AG administration directly promotes the differentiation of rat and human oligodendrocytes cultured under inhibitory conditions. Overall, the data obtained favor targeting the endocannabinoid system to neutralize CSPG accumulation and to enhance oligodendrocyte differentiation.
Increased urocortin 3 levels are associated with the risk of having type 2 diabetes mellitus

Urocortin 3 (UCN3) is a peptide hormone playing a pivotal role in glucose and lipid metabolisms. However, its clinical implications remain unclear. Our aims were to investigate the altered levels of UCN3 in newly diagnosed type 2 diabetes mellitus (nT2DM) patients in comparison to subjects with normal glucose tolerance (NGT) and to determine the presence of any possible link between UCN3 levels and metabolic parameters.
Expression of Matrix Metalloproteinases and Their Tissue Inhibitors in Chronic Rhinosinusitis With Nasal Polyps: Etiopathogenesis and Recurrence

Chronic rhinosinusitis with nasal polyps is a multifactorial disease of the nasal and paranasal sinus mucosa and it includes, as comorbidities, anatomic and morphologic alterations, allergic rhinitis, and immunologic diseases. We investigated matrix metalloproteinases (MMP-2, MMP-7, and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2) concentration in different etiopathogenetical groups of patients with nasal polyposis (NP) in relation to recurrence after sinonasal surgery. The study group consisted of 45 patients with NP (those with allergic rhinitis, nonallergic rhinitis and asthma or nonallergic rhinitis, and obstruction of osteomeatal complex [OMC]) who underwent endonasal sinus surgery. We also collected 10 patients who underwent septoplasty as control. Immunohistochemistry of nasal mucosa fragments, Western blotting, and polymerase chain reaction analysis showed increased MMPs levels (MMP-9 more than MMP-2 and MMP-7) and decreased tissue inhibitors of MMPs levels (TIMP-1 less than TIMP-2), in patients with chronic rhinosinusitis with nasal polyps compared with control group, in particular in patients with nonallergic rhinitis and asthma compared to those with allergic rhinitis and nonallergic rhinitis and obstruction of OMC. We observed a higher risk of recurrence in patients with nonallergic rhinitis and asthma than in those with allergic rhinitis and nonallergic rhinitis and obstruction of OMC after 36 months from surgery. In this research, we evaluated pathogenesis of NP related to MMPs and their inhibitors concentrations in polypoid tissue.
[Effects of the Fomes officinalis Ames. polysaccharides on anti-fatigue and hypoxia tolerance in mice].

OBJECTIVE To study the effects of Fomes officinalis Ames. polysaccharides(FOPS) on anti-fatigue and hypoxia tolerance in mice. METHODS Forty-eight mice were randomly divided into control group, low-dose, middle-dose and high-dose group of FOPS (100, 200, 400 mg/kg). All mice were orally administered by 0.20 ml/10 g, once a day for 21 consecutive days. The effects of different doses of FOPS on the loaded-swimming time, the content of serum urea nitrogen, the blood lactic acid, the hepatic glycogen and the muscle glycogen after exercise, the survival time under hypoxia at normal pressure and the maintenance time after decapitation were observed. RESULTS FOPS could significantly prolong the loaded-swimming time, decrease the contents of serum urea nitrogen , blood lactic acid and increase the contents of hepatic glycogen and muscle glycogen, significantly prolong the survival time under hypoxia and the maintenance time after decapitation comparing with the control group. Compared with the control group, FOPS could prolong the weight-bearing swimming time, anti-hypoxia survival time and respiratory maintenance time of mice after decapitation in a dose-dependent manner (P＜0.05 or 0.01). FOPS could decrease the contents of serum urea nitrogen and blood lactic acid, and increase the contents of hepatic glycogen and muscle glycogen in exercise mice, and most of them were significantly different (P＜0.05) or extremely significant (P＜0.01). CONCLUSION FOPS has anti-fatigue effects and can improve hypoxia tolerance.
Long-term Outcome in Severe Left Ventricular Primary Graft Dysfunction Post Cardiac Transplantation Supported by Early Use of Extracorporeal Membrane Oxygenation

Background. Severe primary graft dysfunction (PGD) is the leading cause of early death following cardiac transplantation. The early use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) may facilitate graft rescue. However, the additional risks of its use are unknown. Methods. We retrospectively reviewed the medical records of all adult patients who underwent cardiac transplantation from January 2009 to February 2016 at St Vincent’s Hospital, Sydney, to evaluate risk factors for the use of VA-ECMO and related morbidity and long-term survival. Results. One hundred ninety-two transplanted patients were identified, 49 (25%) of whom developed left or biventricular PGD requiring VA-ECMO. The total operation time (median 495 [interquartile range 139.8] versus 412.8 [132] min, P < 0.001), cardiopulmonary bypass time (220 [63] versus 176 [73] min, P < 0.001) and the presence of a previous sternotomy (29 [59%] versus 51 [36%], P = 0.019) were associated with the use of VA-ECMO. One-year survival in the VA-ECMO cohort was 71%. After a median follow-up time of 696 days (interquartile range 1201 d), survival was significantly higher in the non-ECMO group (P = 0.004) but not when conditioned on hospital survival (P = 0.34). Patients with shorter than median ECMO runtime (<108 h) had a similar long-term survival to patients who did not require ECMO (P = 0.559). In the ECMO cohort, multivariable logistic regression revealed baseline creatinine in µmol/L (odds ratio 0.99 [95% confidence interval 0.99-1.00], P = 0.019) and duration of ECMO support in days (odds ratio 0.65 [95% confidence interval 0.44-0.97], P = 0.034) were inversely and independently associated with 1-year survival. Conclusions. Short- and long-term survival of PGD supported with VA-ECMO was better than previously described. Early recovery of PGD on VA-ECMO support negates its negative impact on short- and long-term survival.
Sources of Variability in Pediatric Head Computed Tomography Use Among Emergency Departments in New Jersey.

OBJECTIVE Published guidelines have been developed to limit ionizing radiation exposure in children related to diagnostic computed tomography (CT). This study examines the sources of variability in head CT use in children in emergency departments (EDs) in New Jersey despite the presence of such consensus recommendations. METHODS The New Jersey Hospital Association (NJHA) Clinical Repository was queried for study data on all patients younger than 18 years discharged from the ED over a 1-year period. Patient information collected included: treating hospital, patient age, discharge diagnosis, use of head CT, children's hospital (CH) certification, presence of licensed in-patient pediatric beds, association with a hospital system and hospital annual pediatric ED volume. A potential diagnosis requiring a head CT (PDRCT) was defined as one of the following discharge diagnoses: Head Injury, Seizure, Syncope or Headache. Analysis of CT use per 10,000 ED visits was performed through ANOVA, analysis of means for variances, and χ. RESULTS A total of 735,866 ED visits were examined with 16,942 (2.3%) undergoing head CTs. Mean Pediatric Head CT use per 10,000 ED visits for the state was 275 (±16; range, 27-640). During the study period 47,169 (6.4%) ED visits met the PDRCT criteria, 11,495 (27%) of which underwent head CTs. Mean Pediatric Head CT use in this group per 10,000 PDRCT visits was 2948 (±152; range, 728-5806). Characteristics associated with lowest use of head CTs in the PDRCT group included: ED census greater than 10,000 visits per year, CH designation, and younger patient. The presence of in-patient pediatric beds and association with a hospital system with or without an in system CH were not associated with lower head CT use. CONCLUSIONS Despite existing recommendation regarding head CTs in children, there exists a large degree of variability in use of this diagnostic study in EDs in New Jersey.
End-of-life management in intensive care units: a multicentre observational prospective cohort study.

BACKGROUNDS The study was conducted to evaluate intensive care unit (ICU) patients that ultimately died but could have met criteria for end-of-life management/palliative care (ELM-PC), and to analyse the application of components of palliative care, either "unperformed procedures" or elements of "futile/unnecessary treatment". METHODS An observational prospective cohort in five ICUs in Southern Brazil. Adult patients who died were evaluated, searching for criteria for ELM-PC. The correct application of nine preselected items by the ICU team was studied. RESULTS Among 253 admissions, 52 patients died; among these, 38.5% met criteria for ELM-PC. Among ELM-PC candidates (n = 20), the ELM-PC was started later (after day 3) in 60%, and only three patients received adequate palliative care. "Analgesia" and "daily family interviews" were the most correctly applied ELM-PC elements. "Terminal extubation/weaning" was not performed in any of the patients. A reduction in the lifespan from the onset of ELM-PC to death was observed in patients who underwent "correct" interventions - 66.6% died on the first day of ELM-PC. CONCLUSIONS In a patient cohort from a low-medium-income country, one-third of patients who died in the ICU had criteria (indications) for ELM-PC; however, the palliative care was adequately performed for only 15% of patients, with great heterogeneity and delays regarding its initiation.
Extracorporeal Membrane Oxygenation in the Perioperative Care of the Lung Transplant Patient

Lung transplantation (LT) is definitive therapy for end-stage lung disease. Donor allocation based on medical urgency has led to an increased trend in the transplantation of sicker and older patients. Mechanical ventilation (MV) formerly was the only method of bridging high-acuity patients to LT. When the physiological demands of ventilatory support exceeds the capability of MV, extracorporeal membrane oxygenation (ECMO) may become necessary. Recent improvements in ECMO technology and component design have led to a resurgence of interest in its use before, during, and after LT. Survival with ECMO as a bridge to LT has improved over time, now with many centers reporting little or no difference in outcomes, and some even reporting better outcomes, as compared with MV. Extracorporeal life support may also be used intraoperatively. In many studies to date, ECMO or cardiopulmonary bypass (CPB) has been reserved for patients who became hemodynamically unstable during the procedure or patients who could not tolerate single-lung ventilation. Both methods of support are fraught with potential complications. However, multiple studies comparing ECMO with CPB have shown that intraoperative use of ECMO resulted in improved outcomes and overall survival as well as lower rates of bleeding complications. In order to further reduce complications associated with ECMO, planned intraoperative ECMO use is occasionally reserved for high-risk patients who might otherwise require CPB. Future studies will need to improve patient selection to fully take advantage of the use of ECMO in LT while minimizing its costs.
Methylenedioxymethamphetamine-like discriminative stimulus effects of seven cathinones in rats

Synthetic cathinone derivatives are commonly considered quasi-legal alternatives for stimulant drugs, such as cocaine and methamphetamine, but some derivatives are increasingly being detected in club drug formulations of Ecstasy or ‘Molly’ as substitutes for methylenedioxymethamphetamine (±-MDMA). Although several studies have evaluated the psychostimulant-like effects of synthetic cathinones, few cathinone compounds have been assessed for MDMA-like activity. In order to determine their likelihood of interchangeability with entactogenic club drugs, the discriminative stimulus effects of methcathinone, 4-fluoromethcathinone, 4-methylmethcathinone, 4-methylethcathinone, 3-fluoromethcathinone, pentedrone, and ethylone were assessed in Sprague–Dawley rats trained to discriminate 1.5 mg/kg racemic methylenedioxymethamphetamine (±-MDMA) from vehicle. Methamphetamine and the cathinones 4-fluoromethcathinone, 4-methylmethcathinone, 4-methylethcathinone, 3-fluoromethcathinone, pentedrone, and ethylone fully substituted for the discriminative stimulus effects of ±-MDMA. In contrast, methcathinone produced a maximum of only 43% ±-MDMA-appropriate responding and higher doses suppressed responding. Most, but not all of the cathinone compounds tested have discriminative stimulus effects similar to those of MDMA as well as psychostimulant-like effects; however, the potency of MDMA versus psychostimulant substitution varies substantially among the compounds, suggesting that a subset of synthetic cathinones are more MDMA-like than psychostimulant-like. These findings further highlight the highly-variable pharmacology of this class of compounds and suggest that those cathinones with MDMA-like effects may also have increased use as club drugs.
From Policy Statement to Practice: Integrating Social Needs Screening and Referral Assistance With Community Health Workers in an Urban Academic Health Center

Purpose: Social and economic factors have been shown to affect health outcomes. In particular, social determinants of health (SDH) are linked to poor health outcomes in children. Research and some professional academies support routine social needs screening during primary care visits. Translating this recommendation into practice remains challenging due to the resources required and dearth of evidence-based research to guide health center level implementation. We describe our experience implementing a novel social needs screening program at an academic pediatric clinic. Methods: The Community Linkage to Care (CLC) pilot program integrates social needs screening and referral support using community health workers (CHWs) as part of routine primary care visits. Our multidisciplinary team performed process mapping, developed workflows, and led ongoing performance improvement activities. We established key elements of the CLC program through an iterative process We conducted social needs screens at 65% of eligible well-child visits from May 2017 to April 2018; 19.7% of screens had one or more positive responses. Childcare (48.8%), housing quality and/or availability (39.9%), and food insecurity (22.8%) were the most frequently reported needs. On average, 76% of providers had their patients screened on more than half of eligible well-child visits. Discussion: Our experience suggests that screening for social needs at well-child visits is feasible as part of routine primary care. We attribute progress to leveraging resources, obtaining provider buy-in, and defining program components to sustain activities.