Miracle-dz/UniFAR-FTUs huggingface dataset:
Bile acid-activated macrophages promote biliary epithelial cell proliferation through integrin αvβ6 upregulation following liver injury.

Cholangiopathies caused by biliary epithelial cell (BEC) injury represent a leading cause of liver failure. No effective pharmacologic therapies exist, and the underlying mechanisms remain obscure. We aimed to explore the mechanisms of bile duct repair after targeted BEC injury. Injection of intermedilysin into BEC-specific human CD59 (hCD59) transgenic mice induced acute and specific BEC death, representing a model to study the early signals that drive bile duct repair. Acute BEC injury induced cholestasis followed by CCR2+ monocyte recruitment and BEC proliferation. By using microdissection and next generation RNA sequencing, we identified five genes that were most upregulated in proliferating BECs after acute injury including Mapk8ip2, Cdkn1a, Itgb6, Rgs4, and Ccl2. Immunohistochemistry analyses confirmed robust upregulation of integrin αvβ6 (ITGβ6) expression in this BEC injury model, after bile duct ligation, and in patients with chronic cholangiopathies. Deletion of Itgb6 gene attenuated BEC proliferation post-acute bile duct injury. Macrophage depletion or Ccr2-deficiency impaired ITGβ6 expression and BEC proliferation. In vitro experiments revealed that bile-acid activated monocytes promoted BEC proliferation through ITGβ6. Our data suggest that BEC injury induces cholestasis, monocyte recruitment, and induction of ITGβ6, which work together to promote BEC proliferation, and that therefore represent potential therapeutic targets for cholangiopathies.
Cytidine deaminase 435C>T polymorphism relates to gemcitabine-platinum efficacy and hematological toxicity in Chinese non-small-cell lung cancer patients.

CDA 435C>T is reported as a functional SNP but there is no relevant research on the efficacy/hematological toxicity of gemcitabine-platinum treatment in Chinese non-small-cell lung cancer (NSCLC) patients. In this study, 63 patients who received radical resection (stage ⅠB or Ⅲ A) and 100 advanced NSCLC (stage IIIB or IV) patients have been collected, and all were treated with gemcitabine-platinum regimens from February of 2017 to February 2019. CDA 435C>T polymorphisms have been detected by PCR and direct sequencing. CT scan results and blood routine examinations have been collected to evaluate the efficacy and hematological toxicity. Then the relationships have been analyzed about CDA 435C>T. We found that T allele carriers have better therapy response (P < 0.05). Patients carrying CDA 435 C/T or T/T genotypes are statistically associated with a better efficacy (P < 0.05) but are more prone to leukopenia (P < 0.05). Although there is no difference in grade III-IV hematologic toxicity of 163 patients (P > 0.05), in the case of 100 stage IIIB-IV patients, the CDA 435C/T and T/T have an increased risk (P < 0.05). Regarding the CDA 435C>T polymorphism in the Chinese population, in patients with the mutant T allele, gemcitabine is more effective, but they are more prone to suffering from hematological toxicity, especially the late-stage patients.
Clinical Applications of Affinity Chromatography

Liquid chromatographic methods like reversed-phase, normal-phase, size-exclusion, and ion-exchange methods are important in modern clinical laboratories. However, a related technique that is seeing growing use is affinity chromatography. Affinity chromatography can be defined as a liquid chromatographic technique that utilizes ‘‘biological interactions’’ for the separation and analysis of specific analytes in a sample (IUPAC). Examples of these interactions include the binding of an enzyme with an inhibitor, of hormones with receptors, or of an antibody with an antigen. Because of the
On the performance of eleven DFT functionals in the description of the vibrational properties of aluminosilicates

The performance of eleven DFT functionals in describing the equilibrium structure and the vibrational spectra at the Γ point of pyrope (Mg3Al2Si3O12), forsterite (α-Mg2SiO4), α-quartz (α-SiO2) and corundum (α-Al2O3) is discussed. The four systems, for which accurate experimental data are available, are here used as a representative sample of the large aluminosilicates family. Calculations were performed with the periodic ab initio CRYSTAL code by using all-electron Gaussian-type basis sets. All the functionals here considered provide reasonable structural predictions, the hybrid PBE0 giving the least deviation from the experimental unit cell volumes (from −0.3% to +0.6%). At the other extreme, SVWN and SPWLSD (≃−3%) and PBE and PW91 (≃ +3%) provide the largest volume under- and over-estimation, respectively. Vibrational frequencies are more accurate when computed with hybrid functionals, with the best performance provided by B3LYP and WC1LYP (mean absolute differences with respect to experiments evaluated on a set of 134 vibrational frequencies, ||t ≃ 5.5 cm−1). The three recently proposed GGA functionals, PBEsol, SOGGA-PBE and WC-PBE, provide a good description of the vibrational spectra, of the same quality as the one provided by PBE0 and B1WC (||t ≃ 10 cm−1), whereas poorer results are obtained with PBE (||t ≃ 17 cm−1). © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010
Health Services Use and Costs in Individuals with Autism Spectrum Disorder in Germany: Results from a Survey in ASD Outpatient Clinics

Autism spectrum disorders (ASD) are associated with high services use, but European data on costs are scarce. Utilisation and annual costs of 385 individuals with ASD (aged 4–67 years; 18.2% females; 37.4% IQ < 85) from German outpatient clinics were assessed. Average annual costs per person were 3287 EUR, with psychiatric inpatient care (19.8%), pharmacotherapy (11.1%), and occupational therapy (11.1%) being the largest cost components. Females incurred higher costs than males (4864 EUR vs. 2936 EUR). In a regression model, female sex (Cost Ratio: 1.65), lower IQ (1.90), and Asperger syndrome (1.54) were associated with higher costs. In conclusion, ASD-related health costs are comparable to those of schizophrenia, thus underlining its public health relevance. Higher costs in females demand further research.
Candidate name order effects in New Hampshire: Evidence from primaries and from general elections with party column ballots

Research in a few U.S. states has shown that candidates listed first on ballots gain extra votes as a result. This study explored name order effects for the first time in New Hampshire, where such effects might be weak or entirely absent because of high political engagement and the use of party column ballots. In general elections (in 2012 and 2016) for federal offices and the governorship and in primaries (in 2000, 2002, and 2004), evidence of primacy effects appeared in 86% of the 84 tests, including the 2016 presidential race, when Donald Trump gained 1.7 percentage points from first listing, and Hillary Clinton gained 1.5 percentage points. Consistent with theoretical predictions, primacy effects were larger in primaries and for major-party candidates in general elections than for non-major-party candidates in general elections, more pronounced in less publicized contests, and stronger in contests without an incumbent running. All of this constitutes evidence of the reliability and generalizability of evidence on candidate name order effects and their moderators.
Metabolic Dyslipidemia and Cardiovascular Outcomes in Type 2 Diabetes Mellitus: Findings From the Look AHEAD Study

Background Metabolic dyslipidemia (high triglyceride) and low high‐density lipoprotein cholesterol (HDL‐C) is highly prevalent in type 2 diabetes mellitus (T2DM). The extent to which diabetes mellitus–related abnormalities in the triglyceride–HDL‐C profile associates with cardiovascular disease (CVD) risk is incompletely understood. We evaluated the associations of triglyceride and HDL‐C status with CVD outcomes in individuals with T2DM. Methods and Results We analyzed data from 4199 overweight/obese adults with T2DM free of CVD with available data on triglyceride and HDL‐C at baseline (2001–2004) in the Look AHEAD (Action for Health in Diabetes) study. We used Cox proportional models to estimate hazard ratios (HRs) and 95% CIs of: (1) composite CVD outcome (myocardial infarction, stroke, hospitalization for angina, and/or death from cardiovascular causes); (2) coronary artery disease events; and (3) cerebrovascular accidents (stroke). Of the 4199 participants, 62% (n=2600) were women, with a mean age of 58 years (SD, 7), and 40% (n=1659) had metabolic dyslipidemia at baseline. Over a median follow‐up of 9.5 years (interquartile range, 8.7–10.3), 500 participants experienced the composite CVD outcome, 396 experienced coronary artery disease events, and 100 experienced stroke. Low HDL‐C was associated with higher hazards of the composite CVD outcome (HR, 1.36; 95% CI, 1.12–1.64 [P=0.002]) and coronary artery disease events (HR, 1.46; 95% CI, 1.18–1.81 [P=0.001]) but not stroke (HR, 1.38; 95% CI, 0.90–2.11 [P=0.140]). Compared with patients with normal triglyceride and normal HDL, participants with metabolic dyslipidemia had higher risks of the composite CVD outcome (HR, 1.30; 95% CI, 1.03–1.63 [P=0.025]) and coronary artery disease events (HR, 1.48; 95% CI, 1.14–1.93 [P=0.003]) but not stroke (HR, 1.23; 95% CI, 0.74–2.05 [P=0.420]). Conclusions In a large sample of overweight/obese individuals with T2DM, metabolic dyslipidemia was associated with higher risks of CVD outcomes. Our findings highlight the necessity to account for metabolic dyslipidemia in CVD risk stratification among patients with T2DM. Registration URL: https://www.lookaheadtrial. org; Unique identifier: NCT00017953.
Associations between salivary cytokines and periodontal and microbiological parameters in orthodontic patients

Abstract Orthodontic treatment can lead to microbial-induced gingival inflammation and aseptic periodontal inflammations. The aim of this study was to investigate the relationship between salivary pro-inflammatory cytokines levels with gingival health status and oral microbe loads among patients undergoing orthodontic treatment. The present investigation was a cross-sectional study among a sample of 111 consecutive orthodontic patients (mean age 18.4 ± 4.4 years). Clinical examinations were conducted to assess the gingival health status employing the Modified Gingival Index, Gingival Bleeding Index, and Plaque Index. Salivary microbiological assessments of total aerobic and anaerobic bacteria count, streptococci count, and lactobacilli count were undertaken. Saliva immunological assessments included Interleukin-1Beta (IL-1β) and macrophage migration inhibitory factor (MIF) ELISA assays. The mean ± standard deviation of salivary IL-1β was 83.52 ± 85.62 pg/ml and MIF was 4.12 ± 0.96 ng/ml. Moderate positive correlations were found between salivary IL-1β levels and total aerobic and anaerobic bacteria count, streptococci count, and lactobacilli count (r = 0.380–0.446, P < .001), and weak positive correlations between salivary MIF levels and total salivary aerobic and anaerobic bacteria counts (r = 0.249–0.306, P < .01) were observed. A positive correlation was found between salivary IL-1β levels and Bleeding Index (r = 0.216, P < .05). The level of salivary IL-1β positively correlates with oral bacterial load among orthodontic patients; the relationship between inflammatory cytokines and oral microflora deserved further study.
Joint Associations of Prevalent Radiographic Vertebral Fracture and Abdominal Aortic Calcification With Incident Hip, Major Osteoporotic, and Clinical Vertebral Fractures

Prevalent vertebral fractures (PVFx) and abdominal aortic calcification (AAC) are both associated with incident fractures and can be ascertained on the same lateral spine images, but their joint association with incident fractures is unclear. Our objective was to estimate the individual and joint associations of PVFx and AAC with incident major osteoporotic, hip, and clinical vertebral fractures in 5365 older men enrolled in the Osteoporotic Fractures in Men (MrOS) Study, using Cox proportional hazards and Fine and Gray subdistribution hazards models to account for competing mortality. PVFx (Genant SQ grade 2 or 3) and 24‐point AAC score were ascertained on baseline lateral spine radiographs. Self‐reports of incident fractures were solicited every 4 months and confirmed by review of clinical radiographic reports. Compared with men without PVFx and AAC‐24 score 0 or 1, the subdistribution hazard ratio (SHR) for incident major osteoporotic fracture was 1.38 (95% confidence interval [CI] 1.13–1.69) among men with AAC‐24 score ≥2 alone, 1.71 (95% CI 1.37–2.14) for men with PVFx alone, and 2.35 (95% CI 1.75–3.16) for men with both risk factors, after accounting for conventional risk factors and competing mortality. Wald statistics showed improved prediction model performance by including both risk factors compared with including only AAC (chi‐square = 17.3, p < .001) or including only PVFx (chi‐square = 8.5, p = .036). Older men with both PVFx and a high level of AAC are at higher risk of incident major osteoporotic fracture than men with either risk factor alone. Assessing prevalent radiographic vertebral fracture and AAC on the same lateral spine images may improve prediction of older men who will have an incident major osteoporotic fracture, even after accounting for traditional fracture risk factors and competing mortality. © 2021 American Society for Bone and Mineral Research (ASBMR).
Dermoscopic features of post kala azar dermal leishmaniasis

Post kala azar dermal leishmaniasis (PKDL) is a well-known sequela of visceral leishmaniasis (VL) developing either spontaneously or after treatment. Clinical presentation of PKDL include facial erythema, discrete papules, hypopigmented macules, or nodular lesions which are progressive in nature and very rarely heal spontaneously.1 There is a single report describing the dermoscopic features in PKDL, of which yellow tears and erythema were the prominent features.2 Herein we describe dermoscopic features of PKDL lesions in two of our patients which will be an addition to the growing literature of dermoscopy.
Renal metastases from esophageal cancer and retroperitoneal lymphoma detected via chromosome duplications identified by fluorescence in situ hybridization in urine exfoliated cells

Abstract Rationale: Renal-occupying lesions positive for urine fluorescence in situ hybridization (FISH) are usually considered urothelial carcinomas. Here, we describe 2 cases of renal metastases with chromosome duplications in urine exfoliated cells. Patient symptoms: Patient 1, a 56-year-old male with a history of esophageal cancer, was admitted to our hospital on May 2017 after presenting with right back pain with microscopic hematuria for 1 month. Magnetic resonance imaging (MRI) showed right renal space-occupying lesions (5.4 cm × 4.6 cm) and multiple enlarged lymph nodes in the right renal hilum and retroperitoneum. The cystoscopy results were negative, and FISH analysis of urine exfoliated cells was positive, indicative of chromosome 3, 7, and 17 amplifications. Patient 2 was a 50-year-old male who was admitted to our hospital on May 2019 with no obvious cause of abdominal pain and abdominal distension (lasting for 7 days), with a serum creatinine level of 844 μmol/L. Patient 2 had no hematuria or fever, and MRI showed left renal inferior and medial space-occupying lesions, and multiple mesenteric nodules at the junction of the left adrenal gland, retroperitoneum, abdomen, and pelvis, which were partially fused. The tumor lesions were approximately 3.1 cm × 2.3 cm in size. The urine FISH results were positive, indicating chromosome 3, 7, and 17 amplifications. Diagnoses: Both patients were diagnosed with renal tumors with unknown pathology. Interventions: Patient 1 underwent laparoscopic resection of the kidney and ureter, and sleeve cystectomy. The postoperative pathological diagnosis was metastatic keratinized squamous cell carcinoma, with squamous cell carcinoma in the right hilar lymph node. Histological FISH of the primary esophageal cancer and renal metastases were consistent with the urine FISH test results. Patient 2 underwent a biopsy of the left renal inferior and retroperitoneal areas, and was diagnosed with diffuse large B-cell lymphoma. Outcomes: Patient 1 survived 6 months after urological surgery. After treating patient 2 with the R-CHOP regimen and kinase inhibitors, his renal function recovered significantly and the mass become undetectable. Lessons: Our results imply that FISH-positive renal occupying lesions should be considered as potential renal metastases with chromosome aberrations when making a differential diagnosis.
Real-world objects are not stored in holistic representations in visual working memory

When storing multiple objects in visual working memory, observers sometimes misattribute perceived features to incorrect locations or objects. These misattributions are called binding errors (or swaps) and have been previously demonstrated mostly in simple objects whose features are easy to encode independently and arbitrarily chosen, like colors and orientations. Here, we tested whether similar swaps can occur with real-world objects, where the connection between features is meaningful rather than arbitrary. In Experiments 1 and 2, observers were simultaneously shown four items from two object categories. Within a category, the two exemplars could be presented in either the same or different states (e.g., open/closed; full/empty). After a delay, both exemplars from one of the categories were probed, and participants had to recognize which exemplar went with which state. We found good memory for state information and exemplar information on their own, but a significant memory decrement for exemplar–state combinations, suggesting that binding was difficult for observers and swap errors occurred even for meaningful real-world objects. In Experiment 3, we used the same task, but in one-half of the trials, the locations of the exemplars were swapped at test. We found that there are more errors in general when the locations of exemplars were swapped. We concluded that the internal features of real-world objects are not perfectly bound in working memory, and location updates impair object and feature representations. Overall, we provide evidence that even real-world objects are not stored in an entirely unitized format in working memory.
Microengineered Hollow Graphene Tube Systems Generate Conductive Hydrogels with Extremely Low Filler Concentration

The fabrication of electrically conductive hydrogels is challenging as the introduction of an electrically conductive filler often changes mechanical hydrogel matrix properties. Here, we present an approach for the preparation of hydrogel composites with outstanding electrical conductivity at extremely low filler loadings (0.34 S m–1, 0.16 vol %). Exfoliated graphene and polyacrylamide are microengineered to 3D composites such that conductive graphene pathways pervade the hydrogel matrix similar to an artificial nervous system. This makes it possible to combine both the exceptional conductivity of exfoliated graphene and the adaptable mechanical properties of polyacrylamide. The demonstrated approach is highly versatile regarding porosity, filler material, as well as hydrogel system. The important difference to other approaches is that we keep the original properties of the matrix, while ensuring conductivity through graphene-coated microchannels. This novel approach of generating conductive hydrogels is very promising, with particular applications in the fields of bioelectronics and biohybrid robotics.
Physiotherapy via telehealth for acute respiratory exacerbations in paediatric cystic fibrosis

Introduction The demand for Hospital in the Home has increased, especially as an avenue for treatment of respiratory exacerbations. However, a limiting factor of Hospital in the Home efficiency is excess travel. Telehealth can potentially increase in-home access to specialist care such as physiotherapy. This study examined clinical outcomes achieved with a hybrid telehealth model and assessed safety and efficiency. Method This study was an observational benchmarking study of Hospital in the Home physiotherapy episodes of care during respiratory exacerbations between January 2017–June 2019. The participants were young people aged 8–18 years, with cystic fibrosis receiving intravenous antibiotics and bi-daily physiotherapy. The intervention was physiotherapy via either a hybrid model (1× telehealth, 1× face-to-face session) or standard care (2× face-to-face sessions). The outcomes were frequency of return to at least 95% of baseline percentage predicted forced expiratory volume in the first second (ppFEV1), ppFEV1 change, adverse events, travel time and distance saved. Results There were 82 episodes of Hospital in the Home; 41 hybrid and 41 standard care. Return to at least 95% of baseline was achieved in 49% of the hybrid group and 32% of standard care. Median ppFEV1 change was +6% for the hybrid group and +2% standard care. There were no adverse events. Estimated travel time and distance saved was 16,520 min and 12,301.2 km. Conclusion Preliminary information supports a hybrid telehealth physiotherapy model as an alternative to standard care for young people with cystic fibrosis during an exacerbation. Safety of telehealth in conjunction with home visits favoured its use to improve efficiency and capacity without added risk.
Seedling developmental defects upon blocking CINNAMATE-4-HYDROXYLASE are caused by perturbations in auxin transport.

• The phenylpropanoid pathway serves a central role in plant metabolism, providing numerous compounds involved in diverse physiological processes. Most carbon entering the pathway is incorporated into lignin. Although several phenylpropanoid pathway mutants show seedling growth arrest, the role for lignin in seedling growth and development is unexplored. • We use complementary pharmacological and genetic approaches to block CINNAMATE-4-HYDROXYLASE (C4H) functionality in Arabidopsis seedlings and a set of molecular and biochemical techniques to investigate the underlying phenotypes. • Blocking C4H resulted in reduced lateral rooting and increased adventitious rooting apically in the hypocotyl. These phenotypes coincided with an inhibition in auxin transport. The upstream accumulation in cis-cinnamic acid was found to likely cause polar auxin transport inhibition. Conversely, a downstream depletion in lignin perturbed phloem-mediated auxin transport. Restoring lignin deposition effectively reestablished phloem transport and, accordingly, auxin homeostasis. • Our results show that the accumulation of bioactive intermediates and depletion in lignin jointly cause the aberrant phenotypes upon blocking C4H, and demonstrate that proper deposition of lignin is essential for the establishment of auxin distribution in seedlings. Our data position the phenylpropanoid pathway and lignin in a new physiological framework, consolidating their importance in plant growth and development.