Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of a novel liquid biopsy-based ColoScape assay for mutational analysis of colorectal neoplasia and triage of FIT+ patients: a pilot study

Circulating cell free tumour derived nucleic acids are becoming recognised as clinically significant and extremely useful biomarkers for detection of cancer and for monitoring the progression of targeted drug therapy and immunotherapy. Screening programmes for colorectal cancer in Europe use the Fetal Immunochemical Test (FIT) test as a primary screener. FIT+ patients are referred to immediate colonoscopy and the positive predictive value (PPV) is usually 25%. In this article, we report a study employing the ColoScape assay panel to detect mutations in the APC, KRAS, BRAF and CTNNB1 genes, in order to collect preliminary performance indicators and plan a future, larger population study. The assay was evaluated on 52 prospectively collected whole-blood samples obtained from FIT+ patients enrolled in the CRC screening programme of ASL NAPOLI 3 SUD, using colonoscopy as confirmation. The assay’s sensitivity for advanced adenomas was 53.8% and the specificity was 92.3%. The PPV was 70.0% and negative predicitive value (NPV) was 85.7%. Workflow optimisation is essential to maximise sensitivity. Of note, four of the six positive cases missed by ColoScape had a less than suboptimal DNA input (data not shown). Had they been ruled out as inadequate, sensitivity would have increased from 53.8% to 69%. However, as stated previously, this is not a clinical trial, but rather an initial, preliminary technical evaluation. In conclusion this study shows that ColoScape is a promising tool and further studies are warranted in order to validate its use for the triage of FIT+ patients.
Evaluation of Healthcare Use and Clinical Outcomes of Alvimopan in Patients Undergoing Bowel Resection: A Propensity Score-Matched Analysis

BACKGROUND: Postoperative ileus is a significant complication after bowel resection surgeries. Alvimopan is the only US Food and Drug Administration–approved therapy for accelerating the return of bowel function after large- and small-bowel resection. OBJECTIVE: The purpose of this study was to estimate the healthcare use and in-hospital morbidities associated with on-label use of alvimopan in patients undergoing bowel resection surgeries. DESIGN: A retrospective observational propensity-matched cohort study was conducted using a large hospital administrative database. SETTING: The study included inpatient postsurgical patients. PATIENTS: Patients aged ≥18 years undergoing a primary large or small segmental bowel resection with discharge dates between January 2010 and December 2014 were included. INTERVENTIONS: Patients receiving 2 to 15 doses of alvimopan were defined as the treatment cohort, and those without any alvimopan use were included as control subjects. MAIN OUTCOME MEASURES: The primary outcome was postoperative length of stay. Secondary outcomes included postoperative in-hospital morbidities, inpatient mortality, intensive care unit length of stay, discharge disposition, and 30-day readmission. RESULTS: Each propensity-score matched cohort included 18,559 patients. The mean (±SD) postoperative length of stay was 4.62 ± 2.45 days in alvimopan-treated patients compared with 5.24 ± 3.35 days in control subjects (p < 0.001). Alvimopan-treated patients had lower rates of postoperative GI complication (12.15% vs 16.50%; p < 0.001). The rates of urinary tract infections; other postoperative infections; and cardiovascular, pulmonary, thromboembolic, and cerebrovascular events were also lower compared with the control subjects. LIMITATIONS: The study was limited by its inability to generalize to the US population, because the database included a convenience sample of hospital discharges. The identification of patients undergoing bowel resection and their clinical conditions relied on the accuracy and completeness of International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis and procedure coding. There may be a confounding effect by the use of enhanced recovery pathways associated with the use of alvimopan. CONCLUSIONS: The use of alvimopan was associated with a reduction of 0.62 days in postsurgery length of stay and lower rates of postoperative GI complications, infections, and other in-hospital morbidities. See Video Abstract at http://links.lww. com/DCR/A703.
Primary squamous cell carcinoma of the pancreas with effective comprehensive treatment

Rationale: Primary squamous cell carcinoma (SCC) of the pancreas is a rare entity since the pancreas lacks squamous cells. This condition is associated with a poor prognosis, and there is currently no optimal treatment strategy for it. Patient concerns: A 64-year-old female patient with a complaint of epigastric pain for 3 months was referred to our hospital. Diagnoses: She was finally diagnosed with primary SCC of the pancreas with lymph node metastasis on the basis of radiological and pathological findings. Interventions: She received chemoradiation along with targeted therapy and was provided with treatment response evaluation through PET/CT. Outcomes: She eventually died of tumor progression after 8 months. Lessons: Primary SCC of the pancreas is associated with a poor prognosis. Comprehensive therapy and proper radiologic evaluation may facilitate prolonged survival of these patients.
Quality of Life and Psychological Distress of Caregivers' of Stroke People.

PURPOSE Caregivers play a substantial role on support at stroke survivors after acute hospitalization. The aims of the current study were: to determine the quality of life of caregivers of patients with stroke, and to evaluate the predictors of quality of life in caregivers. METHODS It is a cross-sectional study including 150 caregivers of patients with haemorrhagic or ischemic stroke. Participants completed the Greek version of the 12-item Short Form Health Survey assessing caregivers' quality of life. Caregiver burden was measured with the Revised Greek Bakas Caregiving Outcomes Scale, and psychological distress was screened with Greek Hospital Anxiety and Depression Scales. RESULTS A highly negative correlation was found between anxiety (r=0.56) and depression (r=0.59) with physical and mental health (r=0.44, 0.66, r=respectively) from quality of life subscales Physical Component Summary and Mental Component Summary scales. Physical health was influenced by caregivers' health problems (p less than 0.0005), type of stroke (p=0.014), anxiety (p=0.056), depression (p=0.024). Mental health was influenced by caregivers' health problems (p=0.051), burden, anxiety and depression (p less than 0.0005, respectively). CONCLUSIONS Caregivers of people with stroke experience mental disorders and burden negatively affecting their quality of life. Therefore, there is a need to implement strategies which should aim to the management of these problems for the welfare of both patients and their caregivers.
Assessing Amyloid Pathology in Cognitively Normal Subjects Using 18F-Flutemetamol PET: Comparing Visual Reads and Quantitative Methods

Our objective was to determine the optimal approach for assessing amyloid disease in a cognitively normal elderly population. Methods: Dynamic 18F-flutemetamol PET scans were acquired using a coffee-break protocol (a 0- to 30-min scan and a 90- to 110-min scan) on 190 cognitively normal elderly individuals (mean age, 70.4 y; 60% female). Parametric images were generated from SUV ratio (SUVr) and nondisplaceable binding potential (BPND) methods, with cerebellar gray matter as a reference region, and were visually assessed by 3 trained readers. Interreader agreement was calculated using κ-statistics, and semiquantitative values were obtained. Global cutoffs were calculated for both SUVr and BPND using a receiver-operating-characteristic analysis and the Youden index. Visual assessment was related to semiquantitative classifications. Results: Interreader agreement in visual assessment was moderate for SUVr (κ = 0.57) and good for BPND images (κ = 0.77). There was discordance between readers for 35 cases (18%) using SUVr and for 15 cases (8%) using BPND, with 9 overlapping cases. For the total cohort, the mean (±SD) SUVr and BPND were 1.33 (±0.21) and 0.16 (±0.12), respectively. Most of the 35 cases (91%) for which SUVr image assessment was discordant between readers were classified as negative based on semiquantitative measurements. Conclusion: The use of parametric BPND images for visual assessment of 18F-flutemetamol in a population with low amyloid burden improves interreader agreement. Implementing semiquantification in addition to visual assessment of SUVr images can reduce false-positive classification in this population.
Lactobacilli with superoxide dismutase-like or catalase activity are more effective in alleviating inflammation in an inflammatory bowel disease mouse model

Purpose Some lactobacilli, which possess superoxide dismutase-like activity and catalase activity naturally, have strong antioxidative properties. The aim of this study was to identify such strains and check which of them play a crucial role in alleviating intestinal inflammation. Methods We selected two Lactobacillus strains for use in animal studies: L. plantarum 30B (which has the highest catalase activity) and L. acidophilus 900 (which has the highest dismutase-like activity). Forty mice (C57B1/6J) were divided into four experimental groups with ten mice in each group. Group I (control group) was not supplemented with Lactobacillus, group II (catalase group) was orally supplemented with L. plantarum 30B, group III (dismutase-like group) was supplemented with L. acidophilus 900, and group IV (mixed group) was supplemented with both Lactobacillus strains. For 23 days, the temperature and body mass of each mouse were recorded and fecal samples for microbiological examination were collected. On day 23, the animals were sacrificed, and their intestines were removed for microbiological and histopathological studies. Results Compared to the control group, the highest drop in the body temperature was observed in groups II (P<0.05) and IV (P<0.05). Similarly, groups II (P<0.05) and IV (P<0.05) had the highest drop in body mass. Moreover, histopathological evaluation of colon fragments showed intracryptic abscesses in these groups. Group III mice showed most limited degree of inflammation. Conclusion Lactobacillus strains with dismutase-like activity are more effective in alleviating intestinal inflammation than strains producing catalase, suggesting that superoxide anion radical decomposition is crucial in this process.
Microbiota and Derived Parameters in Fecal Samples of Infants with Non-IgE Cow’s Milk Protein Allergy under a Restricted Diet

Cow’s milk protein allergy (CMPA) is the most common food allergy in infancy. Non-IgE mediated (NIM) forms are little studied and the responsible mechanisms of tolerance acquisition remain obscure. Our aim was to study the intestinal microbiota and related parameters in the fecal samples of infants with NIM-CMPA, to establish potential links between type of formula substitutes, microbiota, and desensitization. Seventeen infants between one and two years old, diagnosed with NIM-CMPA, were recruited. They were all on an exclusion diet for six months, consuming different therapeutic protein hydrolysates. After this period, stool samples were obtained and tolerance development was evaluated by oral challenges. A control group of 10 age-matched healthy infants on an unrestricted diet were included in the study. Microbiota composition, short-chain fatty acids, calprotectin, and transforming growth factor (TGF)-β1 levels were determined in fecal samples from both groups. Infants with NIM-CMPA that consumed vegetable protein-based formulas presented microbiota colonization patterns different from those fed with an extensively hydrolyzed formula. Differences in microbiota composition and fecal parameters between NIM-CMPA and healthy infants were observed. Non-allergic infants showed a significantly higher proportion of Bacteroides compared to infants with NIM-CMPA. The type of protein hydrolysate was found to determine gut microbiota colonization and influence food allergy resolution in NIM-CMPA cases.
Auxins and Cytokinins—The Role of Subcellular Organization on Homeostasis

Plant hormones are master regulators of plant growth and development. Better knowledge of their spatial signaling and homeostasis (transport and metabolism) on the lowest structural levels (cellular and subcellular) is therefore crucial to a better understanding of developmental processes in plants. Recent progress in phytohormone analysis at the cellular and subcellular levels has greatly improved the effectiveness of isolation protocols and the sensitivity of analytical methods. This review is mainly focused on homeostasis of two plant hormone groups, auxins and cytokinins. It will summarize and discuss their tissue- and cell-type specific distributions at the cellular and subcellular levels.
Current appraisal of single inhaler triple therapy in COPD

A single inhaler containing inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA)/long-acting muscarinic antagonist (LAMA) is a more convenient way of delivering triple therapy in patients with COPD. Single triple therapy has been shown to be superior at reducing exacerbations and improving quality of life compared to LABA/LAMA, especially in patients with a prior history of frequent exacerbations and blood eosinophilia, who have ICS responsive disease. The corollary is that patients with infrequent exacerbations who are noneosinophilic may be safely de-escalated from triple therapy to LABA/LAMA without loss of control. Pointedly, there is a substantially increased risk of pneumonia associated with the triple therapy containing fluticasone furoate but not beclometasone dipropionate or budesonide. Since triple therapy is also better than ICS/LABA at reducing exacerbations and improving lung function, symptoms, and quality of life, this brings into question the rationale for using ICS/LABA. Hence, we propose a simplified pragmatic decision process based on symptoms, prior to exacerbation history, and blood eosinophils to select which patients should be given a single triple inhaler or LABA/LAMA. Differences in patient preference of inhaler device, formulations and drugs will also determine which triple inhaler prescribers elect to use.
A Magnetically Controlled Soft Microrobot Steering a Guidewire in a Three-Dimensional Phantom Vascular Network

Abstract Magnetically actuated soft robots may improve the treatment of disseminated intravascular coagulation. Significant progress has been made in the development of soft robotic systems that steer catheters. A more challenging task, however, is the development of systems that steer sub-millimeter-diameter guidewires during intravascular treatments; a novel microrobotic approach is required for steering. In this article, we develop a novel, magnetically actuated, soft microrobotic system, increasing the steerability of a conventional guidewire. The soft microrobot is attached to the tip of the guidewire, and it is magnetically steered by changing the direction and intensity of an external magnetic field. The microrobot is fabricated via replica molding and features a soft body made of polydimethylsiloxane, two permanent magnets, and a microspring. We developed a mathematical model mapping deformation of the soft microrobot using a feed-forward approach toward steering. Then, we used the model to steer a guidewire. The angulation of the microrobot can be controlled from 21.1° to 132.7° by using a magnetic field of an intensity of 15 mT. Steerability was confirmed by two-dimensional in vitro tracking. Finally, a guidewire with the soft microrobot was tested by using a three-dimensional (3D) phantom of the coronary artery to verify steerability in 3D space.
Repetitions in Reserve and Rate of Perceived Exertion Increase the Prediction Capabilities of the Load-Velocity Relationship.

Balsalobre-Fernández, C, Muñoz-López, M, Marchante, D, and García-Ramos, A. Repetitions in reserve and rate of perceived exertion increase the prediction capabilities of the load-velocity relationship. J Strength Cond Res XX(X): 000-000, 2018-This study aimed to (a) analyze the relationships between relative load (i.e., %1 repetition maximum; 1RM) and movement velocity, repetitions in reserve (RIR) and rate of perceived exertion (RPE) in competitive powerlifters and (b) examine whether a multiple linear regression model with the movement velocity, RIR, and RPE as predictor variables could improve the goodness of fit of the load-velocity relationship. Ten competitive powerlifters performed an incremental loading test (from 50 to 100% 1RM) on the full-squat, hip-thrust, and bench press exercises. Barbell velocity was measured using a linear position transducer, while RIR and RPE were registered immediately after each set. Velocity (r: 0.747-0.887), RIR (r: 0.857-0.928), and RPE (r: 0.908-0.933) were moderately to highly related to relative load. A higher amount of variance of the relative load was explained when the RIR and RPE were added to velocity in a multiple regression model in comparison with the load-velocity relationship (r: 0.924-0.947). Moreover, it was observed that, in all cases, individual load-velocity, load-RIR, and load-RPE relationships had higher r scores than the generalized load-velocity relationship. Incorporating the RIR and RPE as predictors of the relative load along with movement velocity into a multiple linear regression was shown to provide better estimations of the %1RM than using a linear load-velocity relationship.
A new species of sinistral flatfish of the genus Chascanopsetta (Teleostei: Bothidae) from off Papua New Guinea, western Pacific Ocean.

Left-eyed flounders of the genus Chascanopsetta Alcock 1894 (Bothidae) occur in the Indian, Pacific, and Atlantic oceans at depths ranging from 120 to 1500 meters. They possess some unique features in bothid fishes including a strongly compressed and elongated body and a tremendously large mouth. Currently, nine species of Chascanopsetta are recognized, and three of them (C. micrognatha Amaoka Yamamoto 1984, C. lugubris Alcock 1894 and C. prognatha Norman 1939) are distributed in the West Pacific. We collected 25 specimens of Chascanopsetta during 11 biodiversity expeditions carried out mainly in the West Pacific. Among them, eight specimens taken off Papua New Guinea present morphological features that differ from those of the three nominal species known in the West Pacific. In this study, we examined these eight specimens of unknown affinity and compared their morphology to that of specimens of other congeneric species. Results of these comparisons showed that these specimens represent an undescribed species of Chascanopsetta, named herein, C. novaeguineae sp. nov. The new species resembles C. elski Foroshchuk 1991, which is known only from the Saya de Malha Bank in the western Indian Ocean, in having a high number of gill rakers (> 13). However, the combination of the following characters further distinguishes C. novaeguineae sp. nov. from C. elski: longer jaws, narrower interorbital width, and number of pseudobranches (21-25 vs. 26-27). The DNA sequences from the mitochondrial cytochrome oxidase subunit I (COI) gene from C. novaeguineae sp. nov. and other species were obtained and compared to confirm its taxonomic status and to infer its tentative phylogenetic position within the Chascanopsetta.
Preordering saddle‐point systems for sparse LDLT factorization without pivoting

This paper focuses on efficiently solving large sparse symmetric indefinite systems of linear equations in saddle‐point form using a fill‐reducing ordering technique with a direct solver. Row and column permutations partition the saddle‐point matrix into a block structure constituting a priori pivots of order 1 and 2. The partitioned matrix is compressed by treating each nonzero block as a single entry, and a fill‐reducing ordering is applied to the corresponding compressed graph. It is shown that, provided the saddle‐point matrix satisfies certain criteria, a block LDLT factorization can be computed using the resulting pivot sequence without modification. Numerical results for a range of problems from practical applications using a modern sparse direct solver are presented to illustrate the effectiveness of the approach.
Does pregnancy alter life-course lipid trajectories? Evidence from the HUNT Study in Norway[S]

We examined the association between pregnancy and life-course lipid trajectories. Linked data from the Nord-Trøndelag Health Study and the Medical Birth Registry of Norway yielded 19,987 parous and 1,625 nulliparous women. Using mixed-effects spline models, we estimated differences in nonfasting lipid levels from before to after first birth in parous women and between parous and nulliparous women. HDL cholesterol (HDL-C) dropped by −4.2 mg/dl (95% CI: −5.0, −3.3) from before to after first birth in adjusted models, a 7% change, and the total cholesterol (TC) to HDL-C ratio increased by 0.18 (95% CI: 0.11, 0.25), with no change in non-HDL-C or triglycerides. Changes in HDL-C and the TC/HDL-C ratio associated with pregnancy persisted for decades, leading to altered life-course lipid trajectories. For example, parous women had a lower HDL-C than nulliparous women at the age of 50 years (−1.4 mg/dl; 95% CI: −2.3, −0.4). Adverse changes in lipids were greatest after first birth, with small changes after subsequent births, and were larger in women who did not breastfeed. Findings suggest that pregnancy is associated with long-lasting adverse changes in HDL-C, potentially setting parous women on a more atherogenic trajectory than prior to pregnancy.
A Focused Review on the Treatment of Pediatric Patients with Atypical Antipsychotics.

OBJECTIVES The use of atypical antipsychotic medications in pediatric patients has become more prevalent in recent years. The purpose of this review is to provide a clinically relevant update of recent selected key publications regarding the use of atypical antipsychotics in this population. METHODS Studies reviewed included randomized, double-blind, placebo-controlled medication trials conducted within the past 5 years. A PubMed search was conducted for each of the 11 second-generation antipsychotic medications currently approved by the Food and Drug Administration for use in the United States: clozapine, risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, paliperidone, asenapine, iloperidone, lurasidone, and cariprazine. Trials published in English with subjects 18 years of age and younger were included in this review. Additional studies, chosen for their significance to clinical practice, were also included at the discretion of the authors. RESULTS This review demonstrates that more empiric data are available regarding both the acute efficacy and, to a lesser extent, the longer-term efficacy and tolerability for several of the considered antipsychotic medications. The clinical conditions for which these medications have been studied include schizophrenia, bipolar disorder, Tourette's disorder, and autism spectrum disorder. They have also been used as an adjunctive treatment for disruptive behavior disorders with aggression, which have not responded to treatment with stimulants. CONCLUSION Evidence regarding the efficacy and tolerability of antipsychotic medications for mental health disorders in children and adolescents has expanded exponentially in recent years. However, more information is needed so that evidence-based comparisons between medications can be made. In the future, data enabling the selection of medications based upon individual patient characteristics could potentially lead to greater efficacy and efficiency in treating what are frequently debilitating medical conditions. Maladaptive aggression in children, often treated with antipsychotics, is one such area in which there is a dearth of actual information available to the clinician. It is to be hoped that additional, longer-term studies of these medications will further inform evidence-based practice in clinical settings.