Coupling of response biomarkers between tumor and peripheral blood in patients undergoing chemoimmunotherapy.

Platinum-based chemotherapy in combination with anti-PD-L1 antibodies has shown promising results in mesothelioma. However, the immunological mechanisms underlying its efficacy are not well understood and there are no predictive biomarkers to guide treatment decisions. Here, we combine time course RNA sequencing (RNA-seq) of peripheral blood mononuclear cells with pre-treatment tumor transcriptome data from the single-arm, phase 2 DREAM trial (N = 54).

Impact of chemotherapy on patients with mismatch repair deficient advanced endometrial carcinomas-a meta-analysis.

Background: Chemo-immunotherapy is standard of care for women with recurrent or advanced mismatch repair deficient endometrial carcinoma. However, it is uncertain whether patients with mismatch repair deficient advanced or recurrent endometrial carcinoma derive less benefit from chemotherapy than those with mismatch repair proficient endometrial carcinoma.

Methods: We performed a meta-analysis of randomized controlled trials (RCTs) in advanced or recurrent endometrial carcinoma to determine the difference in the benefit of chemotherapy in mismatch repair deficient vs mismatch repair proficient endometrial carcinoma.

The remarkable larval morphology of Rhaebo nasicus (Werner, 1903) (Amphibia: Anura: Bufonidae) with the erection of a new bufonid genus and insights into the evolution of suctorial tadpoles.

Tadpoles serve as crucial evidence for testing systematic and taxonomic hypotheses. Suctorial tadpoles collected in Guyana were initially assigned to Rhaebo nasicus through molecular phylogeny. Subsequent analysis of larval and adult morphological traits revealed synapomorphies within the clade encompassing R.

Expectations about presence enhance the influence of content-specific expectations on low-level orientation judgements.

Will something appear and if so, what will it be? Perceptual expectations can concern both the presence and content of a stimulus. However, it is unclear how these different types of expectations interact with each other in biasing perception. Here, we tested how expectations about stimulus presence and content differently affect perceptual inference.

Rationale and design of the BeyeOMARKER study: prospective evaluation of blood- and eye-based biomarkers for early detection of Alzheimer's disease pathology in the eye clinic.

Background: Alzheimer's disease (AD) is a common, complex and multifactorial disease that may require screening across multiple routes of referral to enable early detection and subsequent future implementation of tailored interventions. Blood- and eye-based biomarkers show promise as low-cost, scalable and patient-friendly tools for early AD detection given their ability to provide information on AD pathophysiological changes and manifestations in the retina, respectively. Eye clinics provide an intriguing real-world proof-of-concept setting to evaluate the performance of these potential AD screening tools given the intricate connections between the eye and brain, presumed enrichment for AD pathology in the aging population with eye disorders, and the potential for an accelerated diagnostic pathway for under-recognized patient groups.

Head in the clouds: two new microendemic tepui-summit species of Stefania (Anura: Hemiphractidae).

In addition to the type locality (the summit of Aprada-tepui, Bolívar State of Venezuela), the distribution of the egg-brooding frog Stefania satelles was long thought to include several isolated tabletop mountain (tepui) summits surrounding the large Chimantá Massif in Bolívar State (hence the Latin name "satelles"). However, multilocus molecular phylogenetic analyses have revealed that this taxon includes several undescribed morphologically cryptic species, and that S. satelles should be restricted to its type locality.

Determinants of radiographic progression in early psoriatic arthritis: insights from a real-world cohort.

Objective: Persistent articular inflammation in psoriatic arthritis (PsA) is associated with radiographic damage. Despite advances in diagnosis and therapy, radiographic structural damage remains prevalent in PsA. To elucidate this topic, we studied which baseline clinical characteristics determine radiographic progression.

Predictions and errors are distinctly represented across V1 layers.

Popular accounts of mind and brain propose that the brain continuously forms predictions about future sensory inputs and combines predictions with inputs to determine what we perceive. Under "predictive processing" schemes, such integration is supported by the hierarchical organization of the cortex, whereby feedback connections communicate predictions from higher-level deep layers to agranular (superficial and deep) lower-level layers. Predictions are compared with input to compute the "prediction error," which is transmitted up the hierarchy from superficial layers of lower cortical regions to the middle layers of higher areas, to update higher-level predictions until errors are reconciled.

Validity and Efficiency of Progression-Free Survival-2 as a Surrogate End Point for Overall Survival in Advanced Cancer Randomized Trials.

Purpose: Progression-free survival (PFS)-2, defined as the time from randomization to progression on second-line therapy, is potentially a more reliable surrogate than PFS for overall survival (OS), but will require longer follow-up and a larger sample size. We sought to compare the validity and efficiency, defined as proportional increase in follow-up time and sample size, of PFS-2 to PFS.

Methods: We performed an electronic search to identify randomized trials of advanced solid tumors reporting PFS, PFS-2, and OS as prespecified end points.

Diversification of the terrestrial frog genus Anomaloglossus (Anura, Aromobatidae) in the Guiana Shield proceeded from highlands to lowlands, with successive loss and reacquisition of endotrophy.

Two main landscapes emerge from the Guiana Shield: the highlands to the west called the Pantepui region and the Amazonian lowlands to the east, both harbouring numerous endemic species. With 32 currently recognized species, the genus Anomaloglossus stands out among Neotropical frogs as one that diversified only within the Guiana Shield both in the highlands and the lowlands. We present a time-calibrated phylogeny obtained by using combined mitogenomic and nuclear DNA, which suggests that the genus originates from Pantepui where extant lineages started diversifying around 21 Ma, and subsequently (ca.

Influence of Walker Sex and Familiarity on Scent-Marking Behavior of Juvenile and Mature Shelter Dogs.

Many mammals living on farms, in zoos, and in research settings behave differently with familiar people versus strangers, and the sex of the person can also influence interactions. We conducted two studies to examine the influence of a dog's sex and maturity and a walker's sex and familiarity on the behavior of shelter dogs during leash walks. In Study 1 with unfamiliar walkers ( = 113 dogs), we found that mature males urinated at higher rates when walked by a woman than by a man, whereas mature females urinated at similar rates.

Relicts in the mist: Two new frog families, genera and species highlight the role of Pantepui as a biodiversity museum throughout the Cenozoic.

The iconic mountains of the Pantepui biogeographical region host many early-diverging endemic animal and plant lineages, concurring with Conan Doyle's novel about an ancient "Lost World". While this is the case of several frog lineages, others appear to have more recent origins, adding to the controversy around the diversification processes in this region. Due to its remoteness, Pantepui is challenging for biological surveys, and only a glimpse of its biodiversity has been described, which hampers comprehensive evolutionary studies in many groups.

Timed adoptive T cell transfer during chemotherapy in patients with recurrent platinum-sensitive epithelial ovarian cancer.

Background: The presence of T cells and suppressive myeloid cells in epithelial ovarian cancer (EOC) correlate with good and bad clinical outcome, respectively. This suggests that EOC may be sensitive to adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL), provided that immunosuppression by myeloid-derived suppressor cells and M2 macrophages is reduced. Platinum-based chemotherapy can alleviate such immunosuppression, potentially creating a window of opportunity for T cell-based immunotherapy.

Expectation Cues and False Percepts Generate Stimulus-Specific Activity in Distinct Layers of the Early Visual Cortex.

Perception has been proposed to result from the integration of feedforward sensory signals with internally generated feedback signals. Feedback signals are believed to play an important role in driving false percepts, that is, seeing things that are not actually there. Feedforward and feedback influences on perception can be studied using layer-specific fMRI, which we used here to interrogate neural activity underlying high-confidence false percepts while healthy human participants ( = 25, male and female) performed a perceptual orientation discrimination task.

Neoantigen Targetability in Progressive Advanced Melanoma.

Purpose: The availability of (neo)antigens and the infiltration of tumors by (neo)antigen-specific T cells are crucial factors in cancer immunotherapy. In this study, we aimed to investigate the targetability of (neo)antigens in advanced progessive melanoma and explore the potential for continued T-cell-based immunotherapy.

Experimental Design: We examined a cohort of eight patients with melanoma who had sequential metastases resected at early and later time points.

Dedifferentiated umbilical metastases from low grade endometrioid endometrial adenocarcinoma complicated by super-obesity: A case report.

Introduction: Umbilical metastases are uncommon and rarely associated with endometrial cancer. In this report we describe a unique case of a patient with low-grade endometrioid adenocarcinoma (EAC) who developed an umbilical metastasis containing dedifferentiated endometrial carcinoma, in the context of super-morbid obesity with a body mass index (BMI) of 80 kg/m.

Presentation Of Case: A 55-year-old female with atypical endometrial hyperplasia was treated with progestogens whilst attempting weight loss prior to definitive surgery, given the impact of her obesity on surgical risk.

Bones and all: a new critically endangered Pantepui species of Stefania (Anura: Hemiphractidae) and a new osteological synapomorphy for the genus.

The hemiphractid frog genus Stefania is one of the many ancient (near-) endemic lineages of vertebrates inhabiting the biodiverse Pantepui biogeographical region in the Guiana Shield Highlands of northern South America-the famous "Lost World" of Arthur Conan Doyle. Previous molecular analyses of the genus Stefania have indicated that species boundaries and phylogenetic relationships are often incongruent with morphological traits in that clade. A substantial number of "taxonomically cryptic" species, often microendemic, remain to be described.

Large Baseline Optical Imaging Assisted by Single Photons and Linear Quantum Optics.

In this Letter, we show that by combining quantum metrology and networking tools, it is possible to extend the baseline of an interferometric optical telescope and thus improve diffraction-limited imaging of point source positions. The quantum interferometer is based on single-photon sources, linear optical circuits, and efficient photon number counters. Surprisingly, with thermal (stellar) sources of low photon number per mode and high transmission losses across the baseline, the detected photon probability distribution still retains a large amount of Fisher information about the source position, allowing for a significant improvement in the resolution of positioning point sources, on the order of 10  μas.

Stubborn Predictions in Primary Visual Cortex.

Perceivers can use past experiences to make sense of ambiguous sensory signals. However, this may be inappropriate when the world changes and past experiences no longer predict what the future holds. Optimal learning models propose that observers decide whether to stick with or update their predictions by tracking the uncertainty or "precision" of their expectations.