Miracle-dz/UniFAR-FTUs huggingface dataset:
Combination of Ipilimumab and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma

Purpose Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) for metastatic melanoma can be highly effective, but attrition due to progression before TIL administration (32% in prior institutional experience) remains a limitation. We hypothesized that combining ACT with cytotoxic T lymphocyte-associated antigen 4 blockade would decrease attrition and allow more patients to receive TIL. Experimental design Thirteen patients with metastatic melanoma were enrolled. Patients received four doses of ipilimumab (3 mg/kg) beginning 2 weeks prior to tumor resection for TIL generation, then 1 week after resection, and 2 and 5 weeks after preconditioning chemotherapy and TIL infusion followed by interleukin-2. The primary endpoint was safety and feasibility. Secondary endpoints included of clinical response at 12 weeks and at 1 year after TIL transfer, progression free survival (PFS), and overall survival (OS). Results All patients received at least two doses of ipilimumab, and 12 of the 13 (92%) received TIL. A median of 6.5 × 1010 (2.3 × 1010 to 1.0 × 1011) TIL were infused. At 12 weeks following infusion, there were five patients who experienced objective response (38.5%), four of whom continued in objective response at 1 year and one of which became a complete response at 52 months. Median progression-free survival was 7.3 months (95% CI 6.1–29.9 months). Grade ≥ 3 immune-related adverse events included hypothyroidism (3), hepatitis (2), uveitis (1), and colitis (1). Conclusion Ipilimumab plus ACT for metastatic melanoma is feasible, well tolerated, and associated with a low rate of attrition due to progression during cell expansion. This combination approach serves as a model for future efforts to improve the efficacy of ACT.
The relationship between sleep and working memory in children with neurological conditions

ABSTRACT The objective of this study is to investigate whether sleep problems might account for the increased working memory deficits observed in school-aged children with neurological conditions. A novel, transdiagnostic approach to the investigation was chosen, and sleep is treated as a process that can potentially account for working memory difficulties across a range of neurological conditions. Prevalence estimates of sleep problems are also examined. Archival data of 237 children aged 6 to 11 years were collected from a Western Australian statewide neuropsychological service for the period 26 July 2011 to 14 January 2014. Measures of parent-reported sleep quality, snoring, and daytime sleepiness were obtained, in addition to objective measures of verbal and spatial working memory, storage capacity, and processing speed. The results of the data analysis reveal that over one third of participants reported having clinically-significant levels of sleep problems and that poor sleep quality is significantly associated with verbal working memory difficulties. This association remains after partialling out the variance contributed to performance by storage capacity and processing speed, suggesting that sleep is impacting upon an executive component of working memory. No other significant associations are observed. The results suggest that poor sleep quality is associated with an executive component of verbal (rather than spatial) working memory in children with neurological conditions. This has implications for the biological mechanisms thought to underlie the relationship between sleep and cognition in children. The results also demonstrate the clinical utility of a transdiagnostic approach when investigating sleep and cognition in children with neurological conditions.
An Electronic Publication Dedicated to Early Stellar Evolution and Molecular Clouds Correlation between Gas and Dust in Molecular Clouds: L977 Spectral Indices of Centimeter Continuum Sources in Star-forming Regions: Implica- Tions on the Nature of the Outflow Exciting Sources

We report observations of the J = (1–0) C 18 O molecular emission line toward the L977 molecular cloud. To study the correlation between C 18 O emission and dust extinction we constructed a gaussian smoothed map of the infrared extinction measured by Alves et al. (1998) at the same angular resolution (50) as our molecular–line observations. This enabled a direct comparison of C 18 O integrated intensities and column densities with dust extinction over a relatively large range of cloud depth (2 < A V < 30 mag) at 240 positions inside L977. We find a good linear correlation between these two column density tracers for cloud depths corresponding to A V ≤ 10 magnitudes. For cloud depths above this threshold there is a notable break in the linear correlation. Although optically thick C 18 O emission could produce this departure from linearity, CO depletion in the denser, coldest regions of L977 may be the most likely cause of the break in the observed correlation. We directly derive the C 18 O abundance in this cloud over a broad range of cloud depths and find it to be virtually the same as that derived for IC 5146 from the data of Lada et al. (1994). Our results suggest that the use of C 18 O as a column density tracer in molecular clouds can lead to a 10 to 30% underestimation of overall cloud mass. In regions of very high extinction (A V > 10 mag), such as dense cores, our results suggest that C 18 O would be a very poor tracer of mass. We estimate the minimum total column density required to shield C 18 O from the interstellar radiation field to be 1.6 ± 0.5 magnitudes of visual extinction.
Arterial pressure fractality is highly dependent on wave reflection

Wave reflection is an important factor that influences pressure wave morphology and becomes more significant with aging, when cardiovascular risk increases. A pressure wave, measured at any location in the arterial tree, can be decomposed into its forward and backward components and depends on the corresponding amplitude and shifting time delays. Fractal dimension (FD) quantifies the time series complexity defined by its geometrical representation. Objective: The aim of this study was to evaluate the arterial pressure and diameter time series in order to assess the relationship between wave reflection and arterial pressure fractal dimension (FD). Methods: Simultaneous aortic pressure and diameter were measured in 14 conscious dogs. A pair of ultrasonic crystals, a pressure microtransducer and a pneumatic cuff occluder were positioned in the upper third of the descending aorta. Results: Total reflection induced by the occlusion maneuver decreased FD concomitant to the aortic stiffening. Conclusion: Arterial pressure fractality is highly dependent on wave reflection.
Relationship of embryonic development to egg weight, hatch weight, and growth in Japanese quail.

Relationships between egg, embryo, hatch, two-week and four-week body weights of three quail lines differing in growth rate were investigated. Two of the quail lines had previously undergone 29 generations of selection for increased four-week body weight, and the third line was a nonselected control. Selected lines produced heavier eggs, larger 10 to 11 day embryos, and larger chicks. Percent embryo weights were similar for all three lines indicating that correction for egg size eliminated differences in embryo weight. Percentages of hatch weights of selected lines were significantly (P less than .01) larger than comparable percentages in the control line. Correlations between egg and embryo weights were of low magnitude but correlations between egg and hatch weights were large (.7 to .8). Mean regression coefficients for four-week body weight on egg weight were 5.11 and 2.67 g. in trials 1 and 2, respectively. Relationships between egg, embryo, hatch, and body weights of Japanese quail appeared to be of the same general magnitude as those observed in the domestic fowl.
Evaluation of the relationship between the minimum inhibitory concentration of ceftiofur and third-generation cephalosporins in Escherichia coli isolates from food-producing animals

To enable future comparison of the antimicrobial susceptibility data between bacteria obtained from animals and humans, it is necessary to compare the relationships between minimum inhibitory concentrations (MICs) of veterinary and human medicine. We evaluated the relationship between the MIC of ceftiofur (CTF) and the MICs of other third-generation cephalosporins (TGCs): cefotaxime (CTX), cefpodoxime (CPDX), and ceftazidime (CAZ), determined by the broth microdilution method using 118 cefazolin-resistant Escherichia coli isolates from food-producing animals. Using the Clinical and Laboratory Standards Institute criteria, very major classification errors were observed only in CAZ (17.8%, 21 of 118); major and minor errors were observed in all TGCs (CTX: 0.8% [1 of 118] and 9.3% [11 of 118]; CPDX: 9.3% [11 of 118] and 6.8% [8 of 118]; CAZ: 2.5% [3 of 118] and 9.3% [11 of 118], respectively). The Spearman correlation coefficients between the MICs of CTF and CTX, CPDX, and CAZ were 0.765, 0.731, and 0.306, respectively. The sensitivity and specificity values were 100.0% and 81.8% for CTX, 99.0% and 27.3% for CPDX, and 76.0% and 86.4% for CAZ compared with CTF. The C-statistic was 0.978 for CTF and CTX, 0.953 for CPDX, and 0.798 for CAZ. For the TGCs evaluated in our study, testing for CTX susceptibility results showed the highest correlation with the results given when testing for CTF susceptibility.
An Opto-Electronic Sensor for Detecting Soil Microarthropods and Estimating Their Size in Field Conditions

Methods to estimate density of soil-dwelling arthropods efficiently, accurately and continuously are critical for investigating soil biological activity and evaluating soil management practices. Soil-dwelling arthropods are currently monitored manually. This method is invasive, and time- and labor-consuming. Here we describe an infrared opto-electronic sensor for detection of soil microarthropods in the size range of 0.4–10 mm. The sensor is built in a novel microarthropod trap designed for field conditions. It allows automated, on-line, in situ detection and body length estimation of soil microarthropods. In the opto-electronic sensor the light source is an infrared LED. Two plano-convex optical lenses are placed along the virtual optical axis. One lens on the receiver side is placed between the observation space at 0.5–1 times its focal length from the sensor, and another emitter side lens is placed between the observation space and the light source in the same way. This paper describes the setup and operating mechanism of the sensor and the control unit, and through basic tests it demonstrates its potential in automated detection of soil microarthropods. The sensor may be used for monitoring activities, especially for remote observation activities in soil and insect ecology or pest control.
Efficacy and safety of palbociclib in heavily pretreated patients with HR+/HER2- metastatic breast cancer.

AIM CDK4/6 inhibitors in the first and second treatment line in patients with HR+/HER2- metastatic breast cancer (mBC) in combination with hormonal therapy improve progression-free survival. Role of CDK4/6 inhibitors in further treatment lines remains unclear. METHODS Retrospective analysis of 24 HR+/HER2- heavily pretreated mBC patients is presented. RESULTS A total of 58.3% patients achieved stable disease. No objective response was observed. Median progression-free survival was 4.8 months; median overall survival was 11 months. Treatment was well tolerated. CONCLUSION Favorable toxicity profile and efficacy of palbociclib/aromatase inhibitors combination in heavily pretreated luminal mBC patients in this study emphasize the need for further investigation of such drugs in this population.
Optimal approximation of continuous functions by very deep ReLU networks

We consider approximations of general continuous functions on finite-dimensional cubes by general deep ReLU neural networks and study the approximation rates with respect to the modulus of continuity of the function and the total number of weights $W$ in the network. We establish the complete phase diagram of feasible approximation rates and show that it includes two distinct phases. One phase corresponds to slower approximations that can be achieved with constant-depth networks and continuous weight assignments. The other phase provides faster approximations at the cost of depths necessarily growing as a power law $L\sim W^{\alpha}, 0<\alpha\le 1,$ and with necessarily discontinuous weight assignments. In particular, we prove that constant-width fully-connected networks of depth $L\sim W$ provide the fastest possible approximation rate $\|f-\widetilde f\|_\infty = O(\omega_f(O(W^{-2/\nu})))$ that cannot be achieved with less deep networks.
Effects of dietary levels and types of fat on performance and mineral metabolism of broiler chicks.

Two experiments were conducted to investigate the effects of increasing dietary fat level from 0 to 9.0% and sources of supplemental fat (animal-vegetable fat or corn oil) on the performance and mineral metabolism in broiler chicks from day-old to 3 weeks of age. In experiment 1, increasing dietary fat level significantly (P less than .05) increased 3-week body weight and significantly (P less than .01) improved feed efficiency. There was no significant effect of the treatments on bone ash, bone magnesium, phosphorus, manganese, or zinc, although bone calcium content was significantly (P less than .01) reduced with increase in dietary fat level. Plasma minerals were not significantly affected by the diet treatments. In Experiment 2, neither source of fat, dietary calcium, nor vitamin D3 had any significant effect on performance parameters. Calcium and magnesium retention were significantly (P less than .05) reduced by dietary corn oil. Bone ash and magnesium were significantly (P less than .01) reduced when corn oil was the source of dietary fat, and there was a significant interaction between source of fat and dietary calcium level on bone calcium content. Increasing the dietary vitamin D3 from 1600 to 3200 IU/kg significantly (P less than .05) increased bone calcium content. Bone phosphorus, manganese, and zinc content were not significantly affected by the diet treatments. Plasma magnesium, phosphorus, and zinc content were not significantly affected by the diet treatments. It is concluded that increasing dietary fat, although beneficial for growth, was detrimental to calcium retention and bone calcification. Increasing dietary calcium does not seem to alleviate this problem.
Clinical applications of therapeutic phlebotomy

Phlebotomy is the removal of blood from the body, and therapeutic phlebotomy is the preferred treatment for blood disorders in which the removal of red blood cells or serum iron is the most efficient method for managing the symptoms and complications. Therapeutic phlebotomy is currently indicated for the treatment of hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, and nonalcoholic fatty liver disease with hyperferritinemia. This review discusses therapeutic phlebotomy and the related disorders and also offers guidelines for establishing a therapeutic phlebotomy program.
Predation changes the shape of thermal performance curves for population growth rate

Abstract Ectotherms generally demonstrate nonlinear changes in performance (e.g., movement speed, individual growth, population growth) as a function of temperature that are characterized by thermal performance curves (TPC). Predation risk elicits phenotypic and behavioral changes that likewise impact performance measures. We tested whether exposure to predation Orthocyclops modestus impacts the maximum population growth rate (rmax) TPC of the protist Paramecium aurelia. We fit predator and non-predator exposed P. aurelia population growth rates to a function previously shown to best describe Paramecium population growth rate TPC’s (Lactin-2) and compared subsequent parameter estimates between curves. For Paramecium exposed to predation risk, maximum population growth increased more rapidly as temperatures rose and decreased more rapidly as temperatures fell compared to the initial temperature. The area under each TPC curve remained approximately the same, consistent with the idea of a trade-off in performance across temperatures. Our results indicate TPCs are flexible given variation in food web context and that trophic interactions may play an important role in shaping TPCs. Furthermore, this and other studies illustrate the need for a mechanistic model of TPCs with parameters tied to biologically meaningful properties.
The End of the Line: Can Ferredoxin and Ferredoxin NADP(H) Oxidoreductase Determine the Fate of Photosynthetic Electrons?

At the end of the linear photosynthetic electron transfer (PET) chain, the small soluble protein ferredoxin (Fd) transfers electrons to Fd:NADP(H) oxidoreductase (FNR), which can then reduce NADP+ to support C assimilation. In addition to this linear electron flow (LEF), Fd is also thought to mediate electron flow back to the membrane complexes by different cyclic electron flow (CEF) pathways: either antimycin A sensitive, NAD(P)H complex dependent, or through FNR located at the cytochrome b6f complex. Both Fd and FNR are present in higher plant genomes as multiple gene copies, and it is now known that specific Fd iso-proteins can promote CEF. In addition, FNR iso-proteins vary in their ability to dynamically interact with thylakoid membrane complexes, and it has been suggested that this may also play a role in CEF. We will highlight work on the different Fd-isoproteins and FNR-membrane association found in the bundle sheath (BSC) and mesophyll (MC) cell chloroplasts of the C4 plant maize. These two cell types perform predominantly CEF and LEF, and the properties and activities of Fd and FNR in the BSC and MC are therefore specialized for CEF and LEF respectively. A diversity of Fd isoproteins and dynamic FNR location has also been recorded in C3 plants, algae and cyanobacteria. This indicates that the principles learned from the extreme electron transport situations in the BSC and MC of maize might be usefully applied to understanding the dynamic transition between these states in other systems.
Mutations in the netrin-1 gene cause congenital mirror movements

Netrin-1 is a secreted protein that was first identified 20 years ago as an axon guidance molecule that regulates midline crossing in the CNS. It plays critical roles in various tissues throughout development and is implicated in tumorigenesis and inflammation in adulthood. Despite extensive studies, no inherited human disease has been directly associated with mutations in NTN1, the gene coding for netrin-1. Here, we have identified 3 mutations in exon 7 of NTN1 in 2 unrelated families and 1 sporadic case with isolated congenital mirror movements (CMM), a disorder characterized by involuntary movements of one hand that mirror intentional movements of the opposite hand. Given the diverse roles of netrin-1, the absence of manifestations other than CMM in NTN1 mutation carriers was unexpected. Using multimodal approaches, we discovered that the anatomy of the corticospinal tract (CST) is abnormal in patients with NTN1-mutant CMM. When expressed in HEK293 or stable HeLa cells, the 3 mutated netrin-1 proteins were almost exclusively detected in the intracellular compartment, contrary to WT netrin-1, which is detected in both intracellular and extracellular compartments. Since netrin-1 is a diffusible extracellular cue, the pathophysiology likely involves its loss of function and subsequent disruption of axon guidance, resulting in abnormal decussation of the CST.
Do Client Characteristics Really Drive the Big N Audit Quality Effect? New Evidence from Propensity Score Matching

A large auditing literature concludes that Big N auditors provide higher audit quality than non-Big N auditors. Recently, however, a high-profile study suggests that propensity score matching (PSM) on client characteristics eliminates the Big N effect [Lawrence A, Minutti-Meza M, Zhang P (2011) Can Big 4 versus non-Big 4 differences in audit-quality proxies be attributed to client characteristics? Accounting Rev. 86(1):259–286]. We conjecture that this finding may be affected by PSM’s sensitivity to its design choices and/or by the validity of the audit quality measures used in the analysis. To investigate, we examine random combinations of PSM design choices that achieve covariate balance, and four commonly used audit quality measures. We find that the majority of these design choices support a Big N effect for most of the audit quality measures. Overall, our findings show that it is premature to suggest that PSM eliminates the Big N effect. This paper was accepted by Suraj Srinivasan, accounting.
Azole Antifungal Resistance in Candida albicans and Emerging Non-albicans Candida Species

Within the limited antifungal armamentarium, the azole antifungals are the most frequent class used to treat Candida infections. Azole antifungals such as fluconazole are often preferred treatment for many Candida infections as they are inexpensive, exhibit limited toxicity, and are available for oral administration. There is, however, extensive documentation of intrinsic and developed resistance to azole antifungals among several Candida species. As the frequency of azole resistant Candida isolates in the clinical setting increases, it is essential to elucidate the mechanisms of such resistance in order to both preserve and improve upon the azole class of antifungals for the treatment of Candida infections. This review examines azole resistance in infections caused by C. albicans as well as the emerging non-albicans Candida species C. parapsilosis, C. tropicalis, C. krusei, and C. glabrata and in particular, describes the current understanding of molecular basis of azole resistance in these fungal species.
Progress towards the United Nations 90‐90‐90 and 95‐95‐95 targets: the experience in British Columbia, Canada

Antiretroviral therapy (ART) scale‐up is central to the global strategy to control the HIV/AIDS pandemic. To accelerate efforts towards ending the AIDS epidemic, the Joint United Nations Programme on HIV/AIDS released the 90‐90‐90 and 95‐95‐95 targets, which have recently been approved by the United Nations (UN). This study characterizes the province of British Columbia (BC)'s progress towards achieving the UN targets, predicts a trajectory up to 2030 according to each of the individual steps (i.e. %Diagnosed, %On ART and %Virologically Suppressed), and identifies the population sub‐groups at higher risk of not achieving these targets.
Inverse Reinforcement Learning via Nonparametric Spatio-Temporal Subgoal Modeling

Recent advances in the field of inverse reinforcement learning (IRL) have yielded sophisticated frameworks which relax the original modeling assumption that the behavior of an observed agent reflects only a single intention. Instead, the demonstration data is typically divided into parts, to account for the fact that different trajectories may correspond to different intentions, e.g., because they were generated by different domain experts. In this work, we go one step further: using the intuitive concept of subgoals, we build upon the premise that even a single trajectory can be explained more efficiently locally within a certain context than globally, enabling a more compact representation of the observed behavior. Based on this assumption, we build an implicit intentional model of the agent's goals to forecast its behavior in unobserved situations. The result is an integrated Bayesian prediction framework which provides smooth policy estimates that are consistent with the expert's plan and significantly outperform existing IRL solutions. Most notably, our framework naturally handles situations where the intentions of the agent change with time and classical IRL algorithms fail. In addition, due to its probabilistic nature, the model can be straightforwardly applied in an active learning setting to guide the demonstration process of the expert.