Miracle-dz/UniFAR-FTUs huggingface dataset:
Stereotactical fields applied in proton spot scanning mode with range shifter and collimating aperture

Some clinical indications require small fields with sharp lateral dose gradients, which is technically challenging in proton beam therapy. This holds especially true for low-range fields applied with the spot scanning technique, where large beam profiles entering from the beam-line or the insertion of range shifting blocks lead to large lateral gradients. We regard the latter case and solve it by shifting the range shifting block far upstream in conjunction with a collimating aperture close to the patient. The experiments of the current work are based on a commercial proton therapy treatment head designed for several delivery modes. In a research environment of the spot-scanning delivery mode a range shifter is inserted downstream of the scanning magnets in a slot which is usually employed only in a scattering delivery mode. This configuration is motivated by equations assuming a simple model of proton transport. In the experiments lateral dose planes are acquired with a scintillation screen and radiochromic films. Dose distributions are calculated with the Monte Carlo dose engine of the RayStation treatment planning system. We demonstrate that proton fields with 80%–20% lateral dose fall-off values between 1.4 mm and 4.0 mm can be achieved for water equivalent depths between 0 cm and 10 cm. The simulated lateral dose profiles agree with the experimental dose profiles. The sharpening of the field edges is set off by a broadening of the proton spots towards the center of the fields. This limits the clinical application mainly to small fields for which the distal and proximal conformality is of minor importance.
Expression of Semaphorin 3B (SEMA3B) in Various Grades of Endometrial Cancer

Background SEMA3B is known as an inhibitor of angiogenesis and cell proliferation. During carcinogenesis, the loss of SEMA3B function is observed, which results in the progression of neoplastic changes. The aim of this study was to evaluate the expression profile of SEMA3B in endometrial cancer (G1–G3) in comparison to the control group and to assess whether the observed changes in expression could become a molecular marker in endometrial cancer. Material/Methods The study group consisted of 45 patients diagnosed with endometrial cancer (G1, 17; G2, 15; G3, 13). The control group included 15 patients. SEMA3B expression was assessed using the immunohistochemical method. Statistical analysis was carried out using the Statistica 12 PL program (StatSoft, USA). It included the Kruskal-Wallis test and post hoc Dunn’s test (p<0.05). Results Statistically significant differences in the level of SEMA3B expression were observed between all analyzed groups. The expression pattern of SEMA3B was as follows: cancer cells G1>G2>G3; endothelial cells: G3>G1>G2; stromal cells: G2>G1>G3. Conclusions Analysis of the SEMA3B expression profile shows the complexity of neoplastic transformation, which confirms the different expression of SEMA3B in endometrial cancer cells and endothelial cells. The present results and data in the literature data suggest that SEMA3B expression indicates the progression of carcinogenesis in the context of endometrial cancer.
Different and Unequal: A Qualitative Evaluation of Salient Factors Influencing Energy Intake in Adults with Overweight and Obesity

Environmental factors such as food availability and variety can function as cues for overeating in individuals susceptible to overweight or obesity, but relatively little is known about other types of environmental factors that may also be important. This qualitative study compared and contrasted categories of internal and external cues through focus groups and key informant interviews with 24 adults (26 to 77 years old) in the United States who had a body mass index within the healthy range (21.6 ± 2.5 kg/m2) or had overweight or obesity (29.1 ± 3.6 kg/m2). Five domains of external factors influencing food intake were identified: (a) Environmental cues including food availability and variety; (b) normative expectations for dietary intake; (c) food palatability; (d) overt social pressures to overeat; and (e) perceived social expectations around eating. All external domains were noted by participants with overweight or obesity to be challenging, and solutions to avoid overeating were lacking; however, overt social pressures and perceived social expectations appeared to be especially problematic. By explicitly defining different domains of external factors that challenge healthy weight regulation, this study identifies specific targets to address in interventions for healthy weight management.
A structure-based mechanism of cisplatin resistance mediated by glutathione transferase P1-1

Significance The resurgence of platinum-based chemotherapy in the last few years has renewed interest in the field, including clinical studies of cisplatin in combination with resistance modulators. Indeed, cisplatin is one of the most successful anticancer agents, effective against a wide range of solid tumors. However, its use is restricted by side effects and/or by intrinsic or acquired drug resistance. We propose here a new mechanism of cisplatin resistance mediated by glutathione transferase (GST) P1-1, as a cisplatin-binding protein. Our results show that cisplatin can be inactivated by this protein with the aid of 2 solvent-accessible and reactive cysteines. These findings may constitute the basis for the design and synthesis of new GST inhibitors able to circumvent cisplatin resistance. Cisplatin [cis-diamminedichloroplatinum(II) (cis-DDP)] is one of the most successful anticancer agents effective against a wide range of solid tumors. However, its use is restricted by side effects and/or by intrinsic or acquired drug resistance. Here, we probed the role of glutathione transferase (GST) P1-1, an antiapoptotic protein often overexpressed in drug-resistant tumors, as a cis-DDP–binding protein. Our results show that cis-DDP is not a substrate for the glutathione (GSH) transferase activity of GST P1-1. Instead, GST P1-1 sequesters and inactivates cisplatin with the aid of 2 solvent-accessible cysteines, resulting in protein subunits cross-linking, while maintaining its GSH-conjugation activity. Furthermore, it is well known that GST P1-1 binding to the c-Jun N-terminal kinase (JNK) inhibits JNK phosphorylation, which is required for downstream apoptosis signaling. Thus, in turn, GST P1-1 overexpression and Pt-induced subunit cross-linking could modulate JNK apoptotic signaling, further confirming the role of GST P1-1 as an antiapoptotic protein.
Exact algorithms for scheduling multiple families of jobs on parallel machines

In many practical manufacturing environments, jobs to be processed can be divided into different families such that a setup is required whenever there is a switch from processing a job of one family to another job of a different family. The time for setup could be sequence independent or sequence dependent. We consider two particular scheduling problems relevant to such situations. In both problems, we are given a set of jobs to be processed on a set of identical parallel machines. The objective of the first problem is to minimize total weighted completion time of jobs, and that of the second problem is to minimize weighted number of tardy jobs. We propose column generation based branch and bound exact solution algorithms for the problems. Computational experiments show that the algorithms are capable of solving both problems of medium size to optimality within reasonable computational time. © 2003 Wiley Periodicals, Inc. Naval Research Logistics 50: 823–840, 2003.
Comparative transcriptome profiling reveals candidate genes related to insecticide resistance of Glyphodes pyloalis

Abstract Glyphodes pyloalis Walker (Lepidoptera: Pyralididae) is a common pest in sericulture and has developed resistance to different insecticides. However, the mechanisms involved in insecticide resistance of G. pyloalis are poorly understood. Here, we present the first whole-transcriptome analysis of differential expression genes in insecticide-resistant and susceptible G. pyloalis. Clustering and enrichment analysis of DEGs revealed several biological pathways and enriched Gene Ontology terms were related to detoxification or insecticide resistance. Genes involved in insecticide metabolic processes, including cytochrome P450, glutathione S-transferases and carboxylesterase, were identified in the larval midgut of G. pyloalis. Among them, CYP324A19, CYP304F17, CYP6AW1, CYP6AB10, GSTs5, and AChE-like were significantly increased after propoxur treatment, while CYP324A19, CCE001c, and AChE-like were significantly induced by phoxim, suggesting that these genes were involved in insecticide metabolism. Furthermore, the sequence variation analysis identified 21 single nucleotide polymorphisms within CYP9A20, CYP6AB47, and CYP6AW1. Our findings reveal many candidate genes related to insecticide resistance of G. pyloalis. These results provide novel insights into insecticide resistance and facilitate the development of insecticides with greater specificity to G. pyloalis.
Improvement in Quality of Life and Activities of Daily Living in Patients with Liver Cirrhosis with the Use of Health Education and Patient Health Empowerment

Background The management of quality of life (QoL) in patients with cirrhosis is important due to the chronic nature of compensated cirrhosis. The aim of the study was to evaluate the effect of health education using health empowerment theory in patients with liver cirrhosis. Material/Methods Between January 2014 and November 2014, 30 patients who were hospitalized with liver cirrhosis patients were recruited to the study, as the study group. Health education was conducted using the principles of health empowerment theory. Between January 2013 and November 2013, 30 hospitalized cirrhosis patients were recruited as the control group, who were given conventional health education. The QoL scores and Health-Promoting Lifestyle Profile II (HPLP II) scores were evaluated at hospital discharge and at two-month follow-up. The health knowledge awareness rate, activity of daily living (ADL), and health-promoting lifestyles were evaluated. Results On discharge from the hospital, understanding of the major clinical symptoms, etiology, diet and nutrition, use of medication, treatment, and disease awareness rates were significantly higher in the study group compared with the control group (all P<0.05). There were significant differences in ADL scores between the two groups at two-month follow-up (81.5±15.5 vs. 68.5±15.4; P=0.006). All HPLP II scores were higher in the study group compared with the control group at hospital discharge and at two-month follow-up (all P<0.05). Conclusions Patient health empowerment can improve the cognitive level and health behaviors of patients with liver cirrhosis, improve their ability to perform ADL, and improve their QoL.
S-sulfhydration of SIRT3 by hydrogen sulfide attenuates mitochondrial dysfunction in cisplatin-induced acute kidney injury.

AIMS Clinical use of cisplatin, one of the most widely used common and effective chemotherapeutic agents, is limited by its side effects, particularly tubular injury associated nephrotoxicity. Previous studies suggest that Hydrogen sulfide (H2S) alleviates cisplatin-induced acute kidney injury (AKI). However, the underlying mechanism remains largely unclear. RESULTS A single intraperitoneal injection of cisplatin is employed to induce AKI, and the mice exhibits severe kidney dysfunction and histological damage at day 4 after cisplatin injection. Here, we reported that H2S alleviated cisplatin-caused renal toxicity via SIRT3 activation and subsequent improvement of mitochondrial ATP-production. Using a biotin switch assay, we showed that H2S increased S-sulfhydration of SIRT3 and induced deacetylation of its target proteins (OPA1, ATP synthase β and SOD2). These effects of H2S were associated with a reduction of mitochondrial fragmentation, an increase in ATP generation, and less oxidative injury. Notably, the S-sulfhydration of SIRT3 induced by H2S was abrogated when Cys256, Cys259, Cys280, and Cys283 residues on SIRT3 (2 zinc finger domains) were mutated. Innovation and Conclusion: Our data suggest that H2S attenuates cisplatin-induced AKI by preventing mitochondrial dysfunction via SIRT3 sulfhydrylation.
Probing activation‐induced neurochemical changes using optogenetics combined with functional magnetic resonance spectroscopy: a feasibility study in the rat primary somatosensory cortex

Knowledge about biochemical processes is a prerequisite for a better understanding of mechanisms underlying brain activity. 1H functional magnetic resonance spectroscopy (1H‐fMRS) at high magnetic fields allows for the non‐invasive measurement of metabolic changes during brain activation. Optogenetics, on the other hand, has revolutionized the field of neuroscience. It was previously coupled with functional magnetic resonance imaging (fMRI) techniques in rodents enabling population‐specific targeting of cells, investigating brain networks with unprecedented in vivo precision. The coupling of optogenetics and 1H‐fMRS is expected to enhance the specificity of metabolic readouts to validate neuro‐energetic theories underlying brain activity. To date, the feasibility of combining optogenetic stimulation with fMRS has not been explored. We used green laser stimulation delivered through an optical fiber implanted superficially above the primary somatosensory forelimb cortex (S1FL) of rats expressing the C1V1 opsin in excitatory neurons. A protocol for the acquisition of functional 1H MR spectra upon optogenetic stimulation without craniotomy‐induced artefacts was established. Quantification of metabolite concentrations in S1FL upon optogenetic and electrical forepaw stimulation demonstrated significantly increased glutamate levels (+8.8% and +9.9%, p < 0.05 respectively), which were compensated by decreased glutamine levels (−17% and −18%, p < 0.05 respectively). Our results demonstrate for the first time the feasibility of combining optogenetic control and functional MR spectroscopy (o‐fMRS) in the rat somatosensory cortex, opening new possibilities for monitoring the energetic demands of specific cell populations and for exploring the underpinnings of energy metabolism during brain activity.
Wide-band fading channel model for micro-cellular systems

This paper presents a model for a wide-band fading channel for terrestrial mobile applications. The model is based on the results of measurements made in a heavily built-up urban environment of a 25 MHz signal centred at approximately 2.6 GHz. This paper presents the measured impulse response and details the parameter extraction process used to determine the characteristics of the channel. These parameters are used in the channel simulation package and the output of this simulation is compared to the original data.
Driving anger among motor vehicle drivers in China: A cross-sectional survey

Abstract Objective: Driving anger is a common emotion while driving and has been associated with traffic crashes. This study aimed to investigate situations that increase driving anger among Chinese drivers. Methods: A cross-sectional study was conducted among 3,101 drivers in southern China. The translated version of the 33-item Driving Anger Scale (DAS) was used to measure driving anger. Data were collected by face-to-face interviews between June 2016 and September 2016. Results: Confirmatory factor analysis showed that the fit of the original 6-factor model (discourtesy, traffic obstacles, hostile gestures, slow driving, illegal driving, and police presence) was satisfactory, after removing 2 items and allowing 5 error pairs to covary. The model showed satisfactory fit: goodness of fit index (GFI) = 0.90, incremental fit index (IFI) = 0.90, root mean square error of approximation (RMSEA) = 0.06, 90% confidence interval (CI) = 0.061–0.064. Driving anger among Chinese drivers was lower than that in some Western countries. Compared to older and experienced drivers, younger and new drivers were more likely to report driving anger. There was no difference in total reported driving anger between males and females. Additionally, the higher the driver’s anger level was, the more likely he or she was to have had a traffic crash. Conclusion: Driving anger is a common emotion among Chinese drivers and has a strong correlation with aggressive driving behavior and traffic crashes.
A worm in the cytology laboratory: A root cause analysis case study

In the spring of 2018, nematode‐like organisms were first noted at the time of microscopic diagnosis on gynecologic (GYN) and anal pap specimens in our institution's cytopathology department. Due to their morphology and specimen source, we considered a diagnosis of pinworm. However, after identifying at least 30 more cases over 3 months from patients living in variable locations, we started favoring a contaminant. This report studies the steps that were initiated to figure the source of pap smear‐preparation contamination and the molecular investigation to identify the nature of the contaminant.
Peripheral artery disease: the new frontiers of imaging techniques to evaluate the evolution of regenerative medicine

ABSTRACT Introduction: Stem cells (ESC, iPSC, MSC) are known to have intrinsic regenerative properties. In the last decades numerous findings have favored the development of innovative therapeutic protocols based on the use of stem cells (Regenerative Medicine/Cell Therapy) for the treatment of numerous diseases including PAD, with promising results in preclinical studies. So far, several clinical studies have shown a general improvement of the patient’s clinical outcome, however they possess many critical issues caused by the non-randomized design of the limited number of patients examined, the type cells to be used, their dosage, the short duration of treatment and also their delivery strategy. Areas covered: In this context, the use of the most advanced molecular imaging techniques will allow the visualization of very important physio-pathological processes otherwise invisible with conventional techniques, such as angiogenesis, also providing important structural and functional data. Expert opinion: The new frontier of cell therapy applied to PAD, potentially able to stop or even the process that causes the disease, with particular emphasis on the clinical aspects that different types of cells involve and on the use of more innovative molecular imaging techniques now available.
Modelling diastolic dysfunction in induced pluripotent stem cell-derived cardiomyocytes from hypertrophic cardiomyopathy patients.

AIMS Diastolic dysfunction (DD) is common among hypertrophic cardiomyopathy (HCM) patients, causing major morbidity and mortality. However, its cellular mechanisms are not fully understood, and presently there is no effective treatment. Patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) hold great potential for investigating the mechanisms underlying DD in HCM and as a platform for drug discovery. METHODS AND RESULTS In the present study, beating iPSC-CMs were generated from healthy controls and HCM patients with DD. Micropatterned iPSC-CMs from HCM patients showed impaired diastolic function, as evidenced by prolonged relaxation time, decreased relaxation rate, and shortened diastolic sarcomere length. Ratiometric Ca2+ imaging indicated elevated diastolic [Ca2+]i and abnormal Ca2+ handling in HCM iPSC-CMs, which were exacerbated by β-adrenergic challenge. Combining Ca2+ imaging and traction force microscopy, we observed enhanced myofilament Ca2+ sensitivity (measured as dF/Δ[Ca2+]i) in HCM iPSC-CMs. These results were confirmed with genome-edited isogenic iPSC lines that carry HCM mutations, indicating that cytosolic diastolic Ca2+ overload, slowed [Ca2+]i recycling, and increased myofilament Ca2+ sensitivity, collectively impairing the relaxation of HCM iPSC-CMs. Treatment with partial blockade of Ca2+ or late Na+ current reset diastolic Ca2+ homeostasis, restored diastolic function, and improved long-term survival, suggesting that disturbed Ca2+ signalling is an important cellular pathological mechanism of DD. Further investigation showed increased expression of L-type Ca2+channel (LTCC) and transient receptor potential cation channels (TRPC) in HCM iPSC-CMs compared with control iPSC-CMs, which likely contributed to diastolic [Ca2+]i overload. CONCLUSION In summary, this study recapitulated DD in HCM at the single-cell level, and revealed novel cellular mechanisms and potential therapeutic targets of DD using iPSC-CMs.
Outcomes of Triggering the Emergency Response Team at a High-Volume Arthroplasty Center

Background and Aims: Emergency Response Teams have been employed by hospitals to evaluate and manage patients whose condition is rapidly deteriorating. In this study, we aimed to assess the outcomes of triggering the Emergency Response Teams at a high-volume arthroplasty center, determine which factors trigger the Emergency Response Teams, and investigate the main reasons for an unplanned intensive care unit admission following Emergency Response Team intervention. Material and Methods: We gathered data by evaluating all Emergency Response Team forms filled out during a 4-year period (2014–2017), and by assessing the medical records. The collected data included age, gender, time of and reason for the Emergency Response Teams call, and interventions performed during the Emergency Response Teams intervention. The results are reported as percentages, mean ± standard deviation, or median (interquartile range), where appropriate. All patients were monitored for 30 days to identify possible intensive care unit admissions, surgeries, and death. Results: The mean patient age was 72 (46–92) years and 40 patients (62%) were female. The Emergency Response Teams was triggered a total of 65 times (61 patients). The most common Emergency Response Team call criteria were low oxygen saturation, loss or reduction of consciousness, and hypotension. Following the Emergency Response Team call, 36 patients (55%) could be treated in the ward, and 29 patients (45%) were transferred to the intensive care unit. The emergency that triggered the Emergency Response Teams was most commonly caused by drug-related side effects (12%), pneumonia (8%), pulmonary embolism (8%), and sepsis (6%). Seven patients (11%) died during the first 30 days after the Emergency Response Teams call. Conclusion: Although all 65 patients met the Emergency Response Teams call criteria, potentially having severe emergencies, half of the patients could be treated in the arthroplasty ward. Emergency Response Team intervention appears useful in addressing concerns that can potentially lead to unplanned intensive care unit admission, and the Emergency Response Teams trigger threshold seems appropriate as only 3% of the Emergency Response Teams calls required no intervention.
A 1.8 V /spl Delta//spl Sigma/ modulator interface for electret microphone with on-chip reference

A /spl Delta//spl Sigma/ analog-to-digital converter for voltage readout of an electret capacitor microphone is presented. The circuit works at a supply voltage of 1.8 V, suited for next generation mobile phones. An improved-linearity, single-ended high-impedance input, differential output integrator is used to read the 125 mVp audio signal and compare it with a 1-bit digital feedback. The single-loop, fourth order /spl Delta//spl Sigma/ converter operates at 64 times oversampling attaining 80 dB dynamic range and a peak SNDR of 62 dB over a signal bandwidth of 11 kHz.