Miracle-dz/UniFAR-FTUs huggingface dataset:
Histological findings in patients with suspected mediastinal lymphoma relapse according to positive positron emission tomography scan during follow-up: a large retrospective analysis in 96 patients

Abstract Residual masses in patients with mediastinal lymphoma may be positron emission tomography (PET) positive during follow-up also in cases of complete response. The aim of this retrospective study is to verify the reliability of mediastinal PET-positive findings in suggesting disease relapse or progression during follow-up by histological verification. From January 2002 to March 2016, 96 patients with mediastinal lymphoma underwent PET follow-up after front-line treatment. A surgical biopsy was performed to confirm the suspected relapse (for a total of 113 procedures). A lymphoma relapse was diagnosed in 66/102 successful procedures (64.7%). Diagnosis at relapse was concordant with the initial diagnosis in all but 3 cases. Standardized uptake value was significantly higher among patients with relapse than among those who remained in remission (10 versus 5, p < .05). PET scan helps individuate patients with a high suspect of lymphoma relapse and may guide the surgeon to the most suitable target.
The Effect of the Treatment at a Pain Clinic on the Patients’ Assessment of Their Pain Intensity and the Incidence of Mental Disorders in the form of Anxiety, Depression, and Aggression

The aim of the study was to analyze the effect of the treatment given to patients in a pain clinic on their assessment of pain intensity and the incidence of emotional disturbances in the form of anxiety, depression, and aggression. The study was conducted from January 2014 to April 2018 among patients under the care of two Warsaw pain clinics. The study tools were the Hospital Anxiety and Depression Scale—Modified Version (HADS-M) and the Numerical Rating Scale (NRS). The project enrolled 325 patients, with women comprising 60.62% of patients, and the age bracked of 65–79 years comprising 39.38% of patient. The major reasons for attending the pain clinic were osteoarticular pain (44.92%) and neuropathic pain (42.77%). The therapy applied lowered the patients’ pain intensity (4.98 vs. 3.83), anxiety (8.71 vs. 8.12), aggression (3.30 vs. 3.08), and the overall HADS-M score (18.93 vs. 17.90), which shows that the treatment of both the pain symptoms and the associated emotional disturbances in the form of anxiety and aggression was effective. Sex is a factor affecting pain intensity. The level of mental disorders was influenced by the sex and age of the patients and how long they had been treated in the pain clinics.
Prostate-specific antigen glycoprofiling as diagnostic and prognostic biomarker of prostate cancer

The initial part of this review details the controversy behind the use of a serological level of prostate-specific antigen (PSA) for the diagnostics of prostate cancer (PCa). Novel biomarkers are in demand for PCa diagnostics, outperforming traditional PSA tests. The review provides a detailed and comprehensive summary that PSA glycoprofiling can effectively solve this problem, thereby considerably reducing the number of unnecessary biopsies. In addition, PSA glycoprofiling can serve as a prognostic PCa biomarker to identify PCa patients with an aggressive form of PCa, avoiding unnecessary further treatments which are significantly life altering (incontinence or impotence).
Oncogenic Deregulation of Cell Adhesion Molecules in Leukemia

Numerous cell–cell and cell–matrix interactions within the bone marrow microenvironment enable the controlled lifelong self-renewal and progeny of hematopoietic stem and progenitor cells (HSPCs). On the cellular level, this highly mutual interaction is granted by cell adhesion molecules (CAMs) integrating differentiation, proliferation, and pro-survival signals from the surrounding microenvironment to the inner cell. However, cell–cell and cell–matrix interactions are also critically involved during malignant transformation of hematopoietic stem/progenitor cells. It has become increasingly apparent that leukemia-associated gene products, such as activated tyrosine kinases and fusion proteins resulting from chromosomal translocations, directly regulate the activation status of adhesion molecules, thereby directing the leukemic phenotype. These observations imply that interference with adhesion molecule function represents a promising treatment strategy to target pre-leukemic and leukemic lesions within the bone marrow niche. Focusing on myeloid leukemia, we provide a current overview of the mechanisms by which leukemogenic gene products hijack control of cellular adhesion to subsequently disturb normal hematopoiesis and promote leukemia development.
Neural-Network Vector Controller for Permanent-Magnet Synchronous Motor Drives: Simulated and Hardware-Validated Results

This paper focuses on current control in a permanent-magnet synchronous motor (PMSM). This paper has two main objectives: the first objective is to develop a neural-network (NN) vector controller to overcome the decoupling inaccuracy problem associated with the conventional proportional–integral-based vector-control methods. The NN is developed using the full dynamic equation of a PMSM, and trained to implement optimal control based on approximate dynamic programming. The second objective is to evaluate the robust and adaptive performance of the NN controller against that of the conventional standard vector controller under motor parameter variation and dynamic control conditions by: 1) simulating the behavior of a PMSM typically used in realistic electric vehicle applications and 2) building an experimental system for hardware validation as well as combined hardware and simulation evaluation. The results demonstrate that the NN controller outperforms conventional vector controllers in both simulation and hardware implementation.
Patient Characteristics Associated with Making Requests during Primary Care Visits

Background: Patient requests for tests, treatments, or referrals occur frequently during primary care visits and pose challenges for clinicians to address, but little is known about patient characteristics that may predict requests. Objective: To identify patient characteristics associated with a higher rate of patient requests during primary care visits. Design, Setting, and Sample: Cross-sectional analyses of data from 1141 adult patients attending 1319 visits with 56 primary care physicians (including 45 resident and 11 faculty physicians) in an academic family medicine practice. Measurements: Postvisit patient surveys including measures of patient requests for tests, prescriptions, and referrals; sociodemographics; mental and physical health status; symptom bother or worry (3-item scale; range, 3 to 15; Cronbach's α = 0.83); global life satisfaction; medical skepticism; and Five Factor Model personality traits. Results: Patients made 1 or more requests in 867 visits (65.7%). In multivariate analyses of the within-visit request count, the following patient variables were statistically significantly associated with a higher rate of requests: age in years (incidence rate ratio [IRR], 1.01 [95% CI, 1.00 to 1.01]), increased symptom bother or worry (IRR, 1.06 [95% CI, 1.03 to 1.08]), a more extroverted personality (IRR, 1.12 [95% CI, 1.03 to 1.08]), greater life satisfaction (IRR, 1.01 [95% CI, 1.00 to 1.02]), and any prior encounter with the visit physician (IRR, 1.17 [95% CI, 1.04 to 1.32]). Conclusions: Primary care physicians should expect a greater frequency of requests from older patients, patients with greater symptoms bother or worry, more extroverted patients, patients with greater global life satisfaction, and patients with whom they have had prior visits.
Effect of Drug Resistance Mutations on Antiviral Agents in HCV Patients

Background Gene polymorphism of HCV is an important cause of drug resistance to direct-acting antivirals (DAAs). Methods Nested PCR assays were performed to amplify the HCV viral regions of NS3, NS5A and NS5B. Results Major resistant mutation A156S was found in 18.33% of patients with HCV-1b and 64.28% of patients with HCV-2a. HCV-6a patients had a Q80K mutation rate of 95.45%, while the mutation rate of V170I was up to 100%. Mutation frequency varied with the different genotypes of HCV. The proportion of four resistance mutations (M36L, Q80K, A156S, V170I) in different groups were statistically significant (P≤0.05). Resistant mutation Q30R was detected in 116 (72.5%) samples with HCV-1b and -6a, L31M was found in 16 patients, including 12 with HCV-2a and 4 with HCV-6a, H58P was discovered in 42.5% (68/160) of patients with the genotypes Q30R, L31M and H58P; Y93C was found in 9individuals with only HCV-2a. In HCV NS5B sequences, only a few resistant variants were detected, including C316N and S282T. Conclusions Naturally occurring dominant resistance mutations to HCV DAAs pre-existed in treatment-naive patients in China. Mutation frequency and characteristics varied with the HCV genotype.
Population pharmacokinetics of continuous-infusion ceftazidime in febrile neutropenic children undergoing HSCT: implications for target attainment for empirical treatment against Pseudomonas aeruginosa.

OBJECTIVES To conduct a population pharmacokinetic analysis of continuous-infusion ceftazidime in a retrospective cohort of paediatric HSCT patients who were empirically treated for febrile neutropenia (FN) and who underwent therapeutic drug monitoring of ceftazidime steady-state plasma concentrations (Css) for optimization of drug exposure. METHODS A non-parametric approach with Pmetrics was used for pharmacokinetic analysis and covariate evaluation. Monte Carlo simulations were performed to calculate the PTA of the pharmacodynamic determinant of efficacy (Css/MIC ≥4) against Pseudomonas aeruginosa with continuous-infusion ceftazidime dosages of 1-6 g daily. The Css safety threshold was arbitrarily placed at 100 mg/L and advisable dosages were used. RESULTS A total of 46 patients with 70 ceftazidime Css values were included. Estimated glomerular filtration rate (eGFR) and body surface area were the covariates associated with drug clearance. At the EUCAST clinical breakpoint of 8 mg/L, simulations showed that continuous-infusion ceftazidime dosages of 4-6 g daily attained optimal PTAs (>90%) across most of 16 different clinical scenarios based on four classes of eGFR (50-145, 145.1-200, 200.1-286 and 286.1-422 mL/min/1.73 m2) and body surface area (0.30-0.64, 0.65-0.88, 0.89-1.34 and 1.35-1.84 m2). In patients with body surface area 0.30-0.64 m2 and eGFR ≤200 mL/min/1.73 m2 the advisable dose of 3 g daily allowed only suboptimal PTAs (<75%). The cumulative fraction of response against MIC distribution of P. aeruginosa was >87%. CONCLUSIONS Continuous-infusion ceftazidime dosages ranging from 3 to 6 g daily according to different classes of eGFR and body surface area may allow optimized empirical treatment of P. aeruginosa infections in paediatric HSCT patients with FN.
Emerging drugs for the treatment of clostridium difficile

ABSTRACT Introduction: Clostridium difficile or Clostridioides difficile (C. difficile) infection represents the most common cause of healthcare-associated infection. Over the last decades, the incidence and severity of C. difficile infection is rapidly increasing, with a significant impact on morbidity and mortality, and burden on health care system. Orally administered vancomycin and fidaxomicin are the therapeutic options of choice for initial C. difficile infection and fecal microbiota transplant for the recurrence infection. Furthermore, in recent years several new antibiotics with narrow-spectrum activity and low intestinal resorption have been developed, including surotomycin, cadazolid, and ridinilazol, and novel toxoid vaccines are expected to be efficacious in the prevention of C. difficile infection. Areas covered: Literature review was performed to select publications about current guidelines and phase-II/III trials on emerging drugs. These include novel antibiotics, monoclonal antibodies, vaccines, and fecal microbiota transplantation. Expert opinion: We have today a wide spectrum of promising therapeutic possibilities against infection. Pivotal future clinical trials may be crucial in developing effective strategies to optimize outcomes, mainly in high-risk population.
EPHA2 Is a Predictive Biomarker of Resistance and a Potential Therapeutic Target for Improving Antiepidermal Growth Factor Receptor Therapy in Colorectal Cancer

The EPHA2 tyrosine kinase receptor is implicated in tumor progression and targeted therapies resistance. We evaluated EPHA2 as a potential resistance marker to the antiepidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in colorectal cancer. We studied activation of EPHA2 in a panel of human colorectal cancer cell lines sensitive or resistant to anti-EGFR drugs. The in vitro and in vivo effects of ALW-II-41-27 (an EPHA2 inhibitor) and/or cetuximab treatment were tested. Formalin-fixed paraffin-embedded tumor specimens from 82 RAS wild-type (WT) metastatic colorectal cancer patients treated with FOLFIRI + cetuximab as first-line therapy in the CAPRI-GOIM trial were assessed for EPHA2 expression by immunohistochemistry and correlated with treatment efficacy. EPHA2 was differentially activated in colorectal cancer cell lines. Combined treatment with ALW-II-41-27 plus cetuximab reverted primary and acquired resistance to cetuximab, causing cell growth inhibition, inducing apoptosis and cell-cycle G1–G2 arrest. In tumor xenograft models, upon progression to cetuximab, ALW-II-41-27 addition significantly inhibited tumor growth. EPHA2 protein expression was detected in 55 of 82 tumor samples, frequently expressed in less-differentiated and left-sided tumors. High levels of EPHA2 significantly correlated with worse progression-free survival [8.6 months; confidence interval (CI) 95%, 6.4–10.8; vs. 12.3 months; CI 95%, 10.4–14.2; P = 0.03] and with increased progression rate (29% vs. 9%, P = 0.02). A specific EPHA2 inhibitor reverts in vitro and in vivo primary and acquired resistance to anti-EGFR therapy. EPHA2 levels are significantly associated with worse outcome in patients treated with FOLFIRI + cetuximab. These results highlight EPHA2 as a potential therapeutic target in metastatic colorectal cancer.
Long-Term Neurodevelopmental and Functional Outcomes of Infants Born Very Preterm and/or with a Very Low Birth Weight

Background: Birth weight (BW) is often used as a proxy for gestational age (GA) in studies on preterm birth. Recent findings indicate that, in addition to perinatal outcomes, subjects born very preterm (VP; GA < 32 weeks) differ from those with a very low birth weight (VLBW; BW < 1,500 g) in postnatal growth up to their final height. Objective: To study whether neurodevelopmental and functional outcomes at the age of 19 years differ in VP and/or VLBW subjects. Methods: 705 19-year-old subjects from the Project on Preterm and Small-for-Gestational-Age Infants (POPS) cohort were classified as (1) VP+/VLBW+ (n = 354), (2) VP+/VLBW– (n = 144), or (3) VP–/VLBW+ (n = 207), and compared with regard to IQ as assessed with the Multicultural Capacity Test-intermediate level; neuromotor function using Touwen’s examination of mild neurologic dysfunction; hearing loss; self- and parent-reported behavioral and emotional functioning; educational achievement and occupation; and self-assessed health using the Health Utilities Index and the London Handicap Scale. Results: VP+/VLBW– infants, on average, had 3.8-point higher IQ scores (95% confidence interval [CI] 0.5–7.1), a trend towards higher educational achievement, 3.3-dB better hearing (95% CI 1.2–5.4), and less anxious behavior, attention problems, and internalizing behavior than to VP+/VLBW+ subjects. VP–/VLBW+ infants reported 1.8 increased odds (95% CI 1.2–2.6) of poor health compared to VP+/VLBW+ subjects. Conclusions: At the age of 19 years, subjects born VP+/VLBW+, VP+/VLBW–, and VP-/VLBW+ have different neurodevelopmental and functional outcomes, although effect sizes are small. Hence, the terms VP and VLBW are not interchangeable. We recommend, at least for industrialized countries, to base inclusion in future studies on preterm populations on GA instead of on BW.
Interplay between DNA sequence and negative superhelicity drives R-loop structures

Significance Three-stranded R-loop structures form during transcription when the nascent RNA transcript rehybridizes to the template DNA strand. This creates an RNA:DNA hybrid and forces the nontemplate DNA strand into a single-stranded, looped-out state. R-loops form universally over conserved hotspot regions. To date, the physicochemical bases underlying R-loop formation remain unclear. Using a “first-principle” mathematical approach backed by experimental validation, we elucidated the relative contributions of DNA sequence and DNA topology to R-loop formation. Our work provides a quantitative assessment of the energies underlying R-loop formation and of their interplay. It further reveals these structures as important regulators of the DNA topological state. R-loops are abundant three-stranded nucleic-acid structures that form in cis during transcription. Experimental evidence suggests that R-loop formation is affected by DNA sequence and topology. However, the exact manner by which these factors interact to determine R-loop susceptibility is unclear. To investigate this, we developed a statistical mechanical equilibrium model of R-loop formation in superhelical DNA. In this model, the energy involved in forming an R-loop includes four terms—junctional and base-pairing energies and energies associated with superhelicity and with the torsional winding of the displaced DNA single strand around the RNA:DNA hybrid. This model shows that the significant energy barrier imposed by the formation of junctions can be overcome in two ways. First, base-pairing energy can favor RNA:DNA over DNA:DNA duplexes in favorable sequences. Second, R-loops, by absorbing negative superhelicity, partially or fully relax the rest of the DNA domain, thereby returning it to a lower energy state. In vitro transcription assays confirmed that R-loops cause plasmid relaxation and that negative superhelicity is required for R-loops to form, even in a favorable region. Single-molecule R-loop footprinting following in vitro transcription showed a strong agreement between theoretical predictions and experimental mapping of stable R-loop positions and further revealed the impact of DNA topology on the R-loop distribution landscape. Our results clarify the interplay between base sequence and DNA superhelicity in controlling R-loop stability. They also reveal R-loops as powerful and reversible topology sinks that cells may use to nonenzymatically relieve superhelical stress during transcription.
Minimally invasive surgical aortic valve replacement

Minimally invasive aortic valve replacement (MIAVR) is defined as a surgical aortic valve replacement which involves smaller chest incisions as opposed to full sternotomy. It is performed using cardiopulmonary bypass with cardiac arrest. It benefits from potential advantages of a less invasive procedure. To date, over 14 000 MIAVR have been reported in the literature. Due to heterogeneity of the studies, different surgical techniques and mainly the non-randomised nature of these studies comparing MIAVR with conventional aortic valve replacement, it is difficult to draw definitive conclusions. The two main techniques of MIAVR are mini-sternotomy and right anterior mini-thoracotomy. Both techniques with other less common forms of MIAVR will be discussed in this review. The advantages, disadvantages and surgical pitfalls will be discussed. Some of the advantages include shorter intensive care and hospital stay, reduced perioperative blood loss, less pain, improved respiratory function and cosmesis. The possible disadvantage of longer bypass and cross-clamp times may be counter balanced by the recent sutureless and rapid deployment valves. Despite some of the benefits, MIAVR has not been adopted by a significant proportion of the surgeons possibly related to the learning curve and requirements for re-training. As MIAVR becomes more common, randomised trials comparing this technique with transcatheter aortic valve implantation is warranted. In addition, assessing quality of life including return to work and functional capacity is needed.
Graphene-Based Materials as Efficient Photocatalysts for Water Splitting

Photocatalysis has been proposed as one of the most promising approaches for solar fuel production. Among the photocatalysts studied for water splitting, graphene and related materials have recently emerged as attractive candidates due to their striking properties and sustainable production when obtained from biomass wastes. In most of the cases reported so far, graphene has been typically used as additive to enhance its photocatalytic activity of semiconductor materials as consequence of the improved charge separation and visible light harvesting. However, graphene-based materials have demonstrated also intrinsic photocatalytic activity towards solar fuels production, and more specifically for water splitting. The photocatalytic activity of graphene derives from defects generated during synthesis or their introduction through post-synthetic treatments. In this short review, we aim to summarize the most representative examples of graphene based photocatalysts and the different approaches carried out in order to improve the photocatalytic activity towards water splitting. It will be presented that the introduction of defects in the graphenic lattice as well as the incorporation of small amounts of metal or metal oxide nanoparticles on the graphene surface improve the photocatalytic activity of graphene. What is more, a simple one-step preparation method has demonstrated to provide crystal orientation to the nanoparticles strongly grafted on graphene resulting in remarkable photocatalytic properties. These two features, crystal orientation and strong grafting, have been identified as a general methodology to further enhance the photocatalytic activity in graphenebased materials for water splitting. Finally, future prospects in this filed will be also commented.
CD39 Expression Defines Cell Exhaustion in Tumor-Infiltrating CD8+ T Cells-Response.

We are pleased to know that our work has inspired Thelen and colleagues ([1][1]) to study CD39+CD8+ T cells in other human tumor entities. In accordance with our observations in patients with breast cancer ([2][2]), they found an accumulation of CD39+CD8+ T cells in head and neck squamous cell
Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia

The Asia–Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia–Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis.