Miracle-dz/UniFAR-FTUs huggingface dataset:
Immune Checkpoint Inhibitors for Solid Tumors in the Adjuvant Setting: Current Progress, Future Directions, and Role in Transplant Oncology

Simple Summary Immune checkpoint inhibitors (ICIs) are being increasingly used after primary treatment of early-stage tumors to treat any residual disease and prevent recurrence. Herein, we provide a comprehensive review of pivotal clinical studies demonstrating efficacy and safety outcomes when ICIs are utilized after surgery in patients with melanoma, urothelial cancer, renal cell carcinoma, lung cancer, gastroesophageal cancer, and hepatobiliary malignancies. In addition, we highlight the potential role of these agents within the emerging field of transplant oncology. To guide the selection of eligible patients for ICIs, we outline approved and emerging biomarkers that may predict benefit from use of these agents and help monitor response, especially in the absence of visible disease on imaging. Furthermore, we provide real-world considerations with regards to tolerability and cost-effectiveness of these agents and necessary future directions that should be explored to increase the survival outcomes associated with the use of ICIs after surgery. Abstract The rationale for administering immune checkpoint inhibitors (ICIs) in the adjuvant setting is to eradicate micro-metastases and, ultimately, prolong survival. Thus far, clinical trials have demonstrated that 1-year adjuvant courses of ICIs reduce the risk of recurrence in melanoma, urothelial cancer, renal cell carcinoma, non-small cell lung cancer, and esophageal and gastroesophageal junction cancers. Overall survival benefit has been shown in melanoma while survival data are still not mature in other malignancies. Emerging data also show the feasibility of utilizing ICIs in the peri-transplant setting for hepatobiliary malignancies. While ICIs are generally well-tolerated, the development of chronic immune-related adverse events, typically endocrinopathies or neurotoxicities, as well as delayed immune-related adverse events, warrants further scrutiny regarding the optimal duration of adjuvant therapy and requires a thorough risk–benefit determination. The advent of blood-based, dynamic biomarkers such as circulating tumor DNA (ctDNA) can help detect minimal residual disease and identify the subset of patients who would likely benefit from adjuvant treatment. In addition, the characterization of tumor-infiltrating lymphocytes, neutrophil-to-lymphocyte ratio, and ctDNA-adjusted blood tumor mutation burden (bTMB) has also shown promise in predicting response to immunotherapy. Until additional, prospective studies delineate the magnitude of overall survival benefit and validate the use of predictive biomarkers, a tailored, patient-centered approach to adjuvant ICIs that includes extensive patient counseling on potentially irreversible adverse effects should be routinely incorporated into clinical practice.
Constraining dynamical models with observational data

Abstract The spatial distribution and kinematics of stars in the Milky Way are linked through the gravitational potential. Observations of the positions and velocities of stars can therefore be used to measure the mass distribution of the Milky Way. I review steady-state dynamical modeling approaches and illustrate their use in constraining the local matter distribution and the circular velocity curve from the kinematics of stellar tracers. In a few years, Gaia will increase the number of precise positions and velocities by multiple orders of magnitude. I describe some of the dynamical analyses that will be possible with the Gaia data and discuss some promising avenues for the optimal analysis of dynamical data.
Teaching Third Graders about Real‐Life Mathematical Problem Solving: A Randomized Controlled Study

The purpose of this study was to assess the effects of schema‐broadening instruction (SBI), with and without explicit instruction in strategies for tackling the complexities involved in real‐life (RL) math problems, on the math problem solving of third‐grade students. Teachers (n = 30) were assigned randomly to 3 16‐week conditions: control, SBI, and SBI‐RL. Students in their classes (n = 455) were pre‐ and posttested on problem‐solving measures at increasing transfer distances from the problems used for teaching problem solutions, with far transfer mirroring real‐life problems. For the most part, SBI students, with and without RL, improved statistically significantly better than control students, with large effect sizes, but comparably to each other. By contrast, on the least structured real‐life question, paralleling the ambiguities of real‐life problem solving most closely, reliable and large effects favored the SBI‐RL students over SBI and control students, suggesting RL's potential.
Attribution concepts applied to the omega equation

Attributing synoptic development and structure to particular atmospheric features is an important practical problem. In this paper, methods which have been proposed for the attribution of quasi-geostrophic potential vorticity (PV) are extended to the study of sources of vertical motion and the influence of the earth's surface and tropopause. It is shown that, in the presence of an exponential variation of density in the vertical, both the PV and omega equations are governed by an identical form of Helmholtz's equation with a simple radially-symmetric Green's function in layers of constant Brunt–Vaisala frequency. Analytical solutions are given and used to investigate the influence of boundary conditions and source (PV and div Q) distributions, which distinguish the attribution of geopotential and vertical motion. In particular, solutions to the omega equation are markedly affected by dipole cancellation due to the surface boundary condition. The following results are shown: The compressible response to forcing suffers an exponential decay with range compared to the incompressible solution, with a deformation radius of order 2000 km in the mid-latitude troposphere. This behaviour characterizes quasi-geostrophic PV inversion, and is most important in high latitudes. In the absence of boundaries, the incompressible solution correctly represents the response at levels above a source, but overestimates the response beneath the source in proportion to the density. Because of the surface-dipole cancellation, the incompressible solution to the omega equation is accurate for most purposes. The effects of lower level sources of vertical motion (below 700 hPa) are shown to be inhibited and highly localized. The tropopause causes only a small dipole-cancellation in the omega equation, while the tropospheric response to stratospheric sources is strongly inhibited. It is concluded from these results that upper tropospheric and tropopause-level sources tend to dominate the large-scale pattern of vertical motion. Green's function formulation of the problem also suggests source-based approaches to practical diagnostic study which can be related to the above properties.
The development of conditional probability reasoning

Although errors in reasoning about conditional probability have been the focus of interest of psychologists for a long time, the development of conditional reasoning in school students has received little attention. This paper considers the responses of 69 students across grades 3 to 13 in an attempt to model the development of appropriate reasoning skills. Although acknowledging the misconceptions observed by earlier researchers, this study seeks a positivist approach to describe developing understanding by combining mathematical appropriateness with structural complexity. The results of the study are intended to inform other researchers, teachers, and curriculum developers.
Holonomy, twisting cochains and characteristic classes

The primary interest of this paper is to discuss the role of twisting cochains in the theory of characteristic classes. We begin with the homological description of monodromy map, associated with a connection on a trivial bundle over a 1-connected manifold. We regard it as a homomorphism from the algebra of differential forms on the structure group to the algebra of differential forms on the based loopspace of the base, represented by the (reduced) bar-complex of differential forms on it. Next we discuss the notion of "twisting cochains", or more generally "twisting maps", their equivalence relation and give various examples. We show that every twisting map gives rise to a map from the coalgebra to the bar-resolution of the algebra. Further we show that in the case of genuine twisting cochains one can obtain a map from the differential forms on the gauge bundle, associated with the given principal one, to the reduced Hochschild complex of the algebra, of differential forms of the base. Then we discuss a concrete example of a twisting cochain that is defined on the polynomial de Rham forms on an algebraic group and takes values in Cech complex of the base. We show how it can be used to obtain explicit formulas for the Chern classes. We also discuss few modifications of this construction. In the last section we discuss the construction, similar to the one, used by Getzler, Jones and Petrack in their 1991 paper. We show that the map we call "Getzler-Jones-Petrack's map" is homotopy-equivalent to the map that one obtains from a twisting cochain. This enables us to find a generalization of the Bismut's class, which we regard as an image of a suitable element in the differential forms on the group under the Getzler-Jones-Petrack's map.
Flux transfer events: Scale size and interior structure

We report the first direct investigation of the spatial properties of flux transfer events (FTEs) at the Earth's dayside magnetopause. Simultaneous magnetometer and plasma data from the ISEE 1 and 2 satellites are combined to show that magnetosheath FTEs can have a scale size of order an Earth radius in the magnetopause normal direction. We confirm that the magnetic field within the events appears to be twisted, this twisting corresponding to a core field-aligned current of magnitude a few × 105 A. We also show evidence for plasma vorticity in FTEs. The transverse flow and field perturbations accompanying the three events studied obey approximately the Walen relation for a propagating Alfven wave.
Morphology and evolution of cold‐frontal misocyclones

A numerical simulation of an intense, narrow cold‐frontal rain band (NCFR) is presented. This front was associated with localized wind damage as it moved eastwards across the United Kingdom on 24 September 2007. The model used was the operational and research Weather Research and Forecasting‐‐Advanced Research (WRF‐‐ARW) mesoscale model, initialized with Global Forecast System (GFS) operational model output data. The simulation produced a front strongly resembling that seen in radar imagery and conforming to previous studies and conceptual models of the ana‐cold front. In the simulation, a strong surface horizontal wind‐speed maximum is located along the southern flank of a misocyclone; this is shown to be typical of a number that form along the front. Using trajectory analysis, descending cold air parcels, which originate in the rear inflow jet and accelerate within the circulation of the misocyclone, are identified as the origin of the strongest winds. In addition to the localized strong straight‐line winds, circumstantial evidence is presented for the possible occurrence of weak tornadogenesis. The results are discussed in relation to recent studies of NCFRs, squall lines and misocyclones. Copyright © 2009 Royal Meteorological Society
Convergence of the signed output error adaptive identifier

The authors consider an adaptive output error identifier with a signum function in its update kernel. It is shown that the classical strictly positive real (SPR) condition required for the convergence of traditional adaptive identifiers is not enough but that a stronger operator condition called the strict dominant passivity (SDP) condition is needed. An analog of the Kalman Yakubovic Popov lemma is given for the SDP condition, and it is used to outline a convergence proof. <<ETX>>
Figurative Language in Translation: A Study of J.P. Clark’s The Ozidi Saga

The interlingual translation of figurative expressions and idioms is a particularly sensitive task, especially in literary texts where the figurativeness of the language is an inalienable part of the text as a literary piece. Since modern thinking on translation favours fidelity to the source text, the translator is required to maintain – rather than improve, reduce or otherwise alter – the figurative texture of the source text in the target text. In this paper, we investigate the felicity of J.P. Clark’s Izon-English translation in his The Ozidi Saga. We point out that felicitous as Clark’s translation is in general, there are noticeable cases of improvement, impoverishment and alteration, alongside full equivalence, in the figurative texture of the translation when viewed against the Izon text by a sensitive Izon- English bilingual. From this we argue that any form of alteration is a literary disservice to the source text, the source culture and the target audience. We propose that the literary translator should do his utmost to retain the figurative level of the source-text language in the target text, even if this involves literalism and some other violation of the basic code of the target language while annotations and glossaries may be freely employed.
Disability evaluation in patients with Guillain-Barre syndrome and SARS-CoV-2 infection

Objective Several cases of Guillain-Barre syndrome (GBS) associated with SARS-CoV-2 infection have been described. This study illustrated the demographic, clinical, and neurophysiological characteristics of patients with GBS and COVID-19, as well as associated factors with disability at discharge. Materials and methods A retrospective analytical observational study was conducted. It included patients diagnosed with GBS admitted in a national reference center in Peru between 2019 and 2021. Epidemiological, clinical, neurophysiological, and cerebrospinal fluid data were analyzed. A multivariate analysis, using the generalized linear model, was performed, considering the presence of disability at discharge as the dependent variable. Results Eight-one subjects diagnosed with GBS were included. The mean age was 46.8 years (SD: 15.2), with a predominance of males (61.73%). The most frequent clinical presentation was the classic sensory-motor form in 74 cases (91.36%) with AIDP (82.35%) as the most frequent neurophysiological pattern in the group with COVID-19, while AMAN pattern predominated (59.26%) in those without COVID-19 (p = <0.000). The disability prevalence ratio at discharge between subjects with COVID-19 and those without COVID-19 was 1.89 (CI 1.06–3.34), p = 0.030, adjusted for age, sex, and neurophysiological subtype. Conclusion The neurophysiologic subtype AIDP, and a higher disability were associated with the presence of COVID-19. Highlights – The AIDP neurophysiological pattern was the most frequent in patients with COVID-19. – SARS-CoV-2 infection was associated with increased disability at hospital discharge. – The cases of GBS and COVID-19 had a higher level of proteins in CSF.
Charge exchange in a planetary corona: Its effect on the distribution and escape of hydrogen

The theory for a spherical collisionless planetary corona is extended to include charge exchange collisions between H+ and H, which are assumed to constitute intermingled gases with different kinetic temperatures. The treatment is based on the conventional concept of a critical level (or exobase), above which the only collisions considered in the Boltzmann equation are those that resonantly exchange charge. Satellite orbits are not included. Although the geometry treated is an oversimplification for a real planet, numerical examples are given for an idealized earth and Venus. For earth an ion temperature of 4 times the neutral temperature, an ion density at the exobase of 1.4 × 104 cm−3, and a plasmapause at 1.5 RE will raise the escape flux of H by a factor of 6. The total H above the exobase is changed by less than 1%. For Venus the conditions are examined that would account for the peculiar H distribution observed from Mariner 5. The plasma conditions required are not obviously outrageous by terrestrial standards, but the Mariner 5 ionosphere measurements did not show a high plasmapause at, say, 1.25 or 1.5 planetary radii, a fact that might argue against a charge exchange model.
Sensory profiling in classical Ehlers-Danlos syndrome: a case-control study revealing pain characteristics, somatosensory changes, and impaired pain modulation

Pain is one of the most important, yet poorly understood complaints in heritable connective tissue disorders (HCTD) caused by monogenic defects in extracellular matrix molecules. This is particularly the case for Ehlers-Danlos syndromes (EDS), paradigm collagen-related disorders. This study aimed to identify the pain signature and somatosensory characteristics in the rare classical type of EDS (cEDS) caused by defects in type V or rarely type I collagen. We used static and dynamic quantitative sensory testing and validated questionnaires in 19 individuals with cEDS and 19 matched controls. Individuals with cEDS reported clinically relevant pain/discomfort (VAS [≥]5/10 in 32% for average pain intensity the past month) and worse health -related quality of life. Altered sensory profile was found in the cEDS group with higher (p=0.04) detection thresholds for vibration stimuli at the lower limb indicating hypoesthesia, reduced thermal sensitivity with more (p<0.001) paradoxical thermal sensations, and hyperalgesia with lower pain thresholds to mechanical (p<0.001) stimuli at both the upper and lower limbs and to cold (p=0.005) stimulation at the lower limb. Using a parallel conditioned pain paradigm, the cEDS group showed significantly smaller antinociceptive responses (p-value between 0.005 and 0.046) suggestive of impaired endogenous central pain modulation. In conclusion, Individuals with cEDS report chronic pain and worse health-related quality of life, and present altered somatosensory perception. This study is the first to systematically investigate pain and somatosensory characteristics in a genetically defined HCTD and provides interesting insights on the possible role of the ECM in the development and persistence of pain.
Hypertensive adults exhibit lower myelin content: A multicomponent relaxometry and diffusion MRI study

It is unknown whether hypertension plays any role in cerebral myelination. To fill this knowledge gap, we studied ninety cognitively unimpaired adults, age range 40 to 94 years, that are participants in the Baltimore Longitudinal Study of Aging (BLSA) and the Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing (GESTALT) to look for potential associations between hypertension and cerebral myelin content across fourteen white matter brain regions. Myelin content was probed using our advanced multicomponent magnetic resonance (MR) relaxometry method of myelin water fraction (MWF), a direct and specific MR imaging (MRI) measure of myelin content, and longitudinal and transverse relaxation rates (R1 and R2), two highly sensitive MRI metrics of myelin content. We also applied diffusion tensor imaging (DTI) MRI to measure fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AxD) values, which are metrics of cerebral microstructural tissue integrity, to provide contact with previous MRI findings. After adjustment of age, sex, systolic blood pressure, smoking status, diabetes status and cholesterol level, our results indicated that participants with hypertension exhibited lower MWF, FA, R1 and R2 values and higher MD, RD and AxD values, indicating lower myelin content and higher impairment to the brain microstructure. These associations were significant across several white matter regions, particularly in the corpus callosum, fronto-occipital fasciculus, temporal lobes, internal capsules, and corona radiata. These original findings suggest a direct association between myelin content and hypertension, and form the basis for further investigations including longitudinal assessments of this relationship.
THE NEW ZEALAND BUSINESS CYCLE

Our paper is in the spirit of Rex Bergstrom's interests and research in cyclical growth models and his meticulous attention to underlying data series. We develop a new quarterly real GDP series for post–World War II New Zealand, derive a new “benchmark” set of classical business cycle turning points, and establish nonparametric classical cycle characteristics. Markov-switching models, estimated by Gibbs-sampling methods, are used to derive mean growth rate and volatility regimes and to add to existing knowledge. The resulting properties, involving cycle asymmetries, volatility, diversity and duration dependence, and differing mean growth rate and volatility regimes, can be used to underpin a next generation of cyclical growth models for New Zealand, in the Bergstrom tradition.
Schistosoma mansoni infection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses.

The impact of endemic infections on protective immunity is critical to inform vaccination strategies. In this study, we assessed the influence of Schistosoma mansoni infection on host responses in a Ugandan fishing cohort given a Hepatitis B (HepB) vaccine. Concentrations of schistosome-specific circulating anodic antigen (CAA) pre-vaccination showed a significant bimodal distribution associated with HepB titers, which were lower in individuals with high CAA. We established that participants with high CAA had significantly lower frequencies of circulating T follicular helper (cTfh) subpopulations pre- and post-vaccination and higher regulatory T cells (Tregs) post-vaccination. Polarization towards higher frequencies of Tregs: cTfh cells can be mediated by changes in the cytokine environment favoring Treg differentiation. In fact, we observed higher levels of CCL17 and soluble IL-2R pre-vaccination (important for Treg recruitment and development), in individuals with high CAA that negatively associated with HepB titers. Additionally, alterations in pre-vaccination monocyte function correlated with HepB titers, and changes in innate-related cytokines/chemokine production were associated with increasing CAA concentration. We report, that by influencing the immune landscape, schistosomiasis has the potential to modulate immune responses to HepB vaccination. These findings highlight multiple Schistosoma-related immune associations that could explain abrogated vaccine responses in communities with endemic infections.
On Linear and Multiplicative Relations

A theorem on the successive minima of lattices corresponding to the integer solutions of systems of linear equations is proved. As a corollary, theorems on the successive minima are obtained for the set of solutions of equations of the form for fixed in an algebraic number field and for variable equal either to 1 or a root of unity.Bibliography: 13 titles.
Utility of Conventional but Late Pulmonary Artery Banding in Complex Cyanotic Congenital Heart Disease in a Toddler - A Single Case Scenario

Newborns with untreated single ventricles develop pulmonary vascular diseases early in their lives. At that age, during the first eight weeks after birth, clinicians perform pulmonary artery (PA) banding to reduce the blood flow to the lung, decreasing the likelihood of future high vascular resistance or pressure. PA banding is also considered an initial stage in the process of single ventricle palliation procedures. We report a case of a 16-month-old toddler (7 kg) with room air saturation of 82%, diagnosed with tricuspid valve atresia, large atrial and ventricular septal defect, and hypoplastic right ventricle with severe pulmonary arterial hypertension. The baby underwent a successful surgical procedure of PA banding and was discharged after 13 days of hospital stay with a room air saturation of 89%. This case highlighted the benefit of PA banding beyond the stipulated period.