julilili42/papers huggingface dataset:
Experimental investigation of orangutans’ lithic percussive and sharp stone tool behaviours
2022-02-16

Early stone tools, and in particular sharp stone tools, arguably represent one of the most important technological milestones in human evolution. The production and use of sharp stone tools significantly widened the ecological niche of our ancestors, allowing them to exploit novel food resources. However, despite their importance, it is still unclear how these early lithic technologies emerged and which behaviours served as stepping-stones for the development of systematic lithic production in our lineage. One approach to answer this question is to collect comparative data on the stone tool making and using abilities of our closest living relatives, the great apes, to reconstruct the potential stone-related behaviours of early hominins. To this end, we tested both the individual and the social learning abilities of five orangutans to make and use stone tools. Although the orangutans did not make sharp stone tools initially, three individuals spontaneously engaged in lithic percussion, and sharp stone pieces were produced under later experimental conditions. Furthermore, when provided with a human-made sharp stone, one orangutan spontaneously used it as a cutting tool. Contrary to previous experiments, social demonstrations did not considerably improve the stone tool making and using abilities of orangutans. Our study is the first to systematically investigate the stone tool making and using abilities of untrained, unenculturated orangutans showing that two proposed pre-requisites for the emergence of early lithic technologies–lithic percussion and the recognition of sharp-edged stones as cutting tools–are present in this species. We discuss the implications that ours and previous great ape stone tool experiments have for understanding the initial stages of lithic technologies in our lineage.
Final overall survival analysis and organ-specific target lesion assessments with two-year follow-up in CheckMate 9ER: Nivolumab plus cabozantinib versus sunitinib for patients with advanced renal cell carcinoma.
2022-02-16

350 Background: First-line nivolumab plus cabozantinib (N+C) demonstrated superiority over sunitinib (SUN) in the primary disclosure of the phase 3 CheckMate 9ER trial (NCT03141177; 10.6 months minimum follow-up; Choueiri TK et al. N Engl J Med 2021) in patients (pts) with advanced renal cell carcinoma (aRCC). Here, we report the preplanned final overall survival (OS) analysis with updated efficacy and safety in intent-to-treat (ITT) pts, and an exploratory assessment of target lesions by organ site after extended follow-up. Methods: Pts with aRCC (clear cell component) were randomized to N 240 mg every 2 weeks + C 40 mg once daily vs SUN 50 mg once daily (4 weeks of 6-week cycles). The primary endpoint was RECIST v1.1–defined progression-free survival (PFS) by blinded independent central review (BICR) in ITT pts; secondary endpoints included OS, objective response rate (ORR) by BICR, and safety. The preplanned final OS analysis was set to occur after observing 254 events. Maximal reduction of target lung, lymph node, kidney, and liver lesions were evaluated per BICR via post hoc exploratory analyses. Results: After 25.4 months minimum follow-up (median, 32.9 months) for OS in ITT pts, a total of 271 OS events occurred, and N+C continued to demonstrate OS improvement vs SUN (N = 323 vs 328; median 37.7 vs 34.3 months; HR 0.70 [95% CI 0.55–0.90]). PFS (median 16.6 vs 8.3 months; HR 0.56 [95% CI 0.46–0.68]) and ORR (55.7% [95% CI 50.1–61.2] vs 28.4% [95% CI 23.5–33.6]) benefits were maintained with N+C vs SUN, and 12.4% (N+C) vs 5.2% (SUN) of pts had a complete response. Median duration of response was 23.1 months with N+C vs 15.1 months with SUN. A higher percentage of pts experienced any reduction and ≥30% reduction from baseline with N+C vs SUN in target lesions at all organ sites assessed (Table). Among all treated pts, 97.2% (N+C; N = 320) vs 93.1% (SUN; N = 320) had a treatment-related adverse event (TRAE) of any grade (65.0% vs 54.1% had a grade ≥ 3 TRAE). Conclusions: N+C continued to provide survival improvement vs SUN among ITT pts in the final OS analysis, additionally PFS and ORR benefits with N+C were sustained with minimum 2-year follow-up. A higher proportion of pts experienced tumor shrinkage benefit with N+C vs SUN across all 4 organ sites assessed. No new safety signals emerged with extended follow-up in either arm. These results highlight N+C as a first-line treatment for pts with aRCC. Clinical trial information: NCT03141177. [Table: see text]
Complete and Incomplete Resection for Progressive Glioblastoma Prolongs Post-Progression Survival
2022-02-16

Objective The role of resection in progressive glioblastoma (GBM) to prolong survival is still controversial. The aim of this study was to determine 1) the predictors of post-progression survival (PPS) in progressive GBM and 2) which subgroups of patients would benefit from recurrent resection. Methods We have conducted a retrospective bicentric cohort study on isocitrate dehydrogenase ( IDH ) wild-type GBM treated in our hospitals between 2006 and 2015. Kaplan-Maier analyses and univariable and multivariable Cox regressions were performed to identify predictors and their influence on PPS. Results Of 589 patients with progressive IDH wild-type GBM, 355 patients were included in analyses. Median PPS of all patients was 9 months (95% CI 8.0-10.0), with complete resection 12 months (95% CI 9.7-14.3, n=81), incomplete resection 11 months (95% CI 8.9-13.1, n=70) and without resection 7 months (95% CI 06-08, n=204). Multivariable Cox regression demonstrated a benefit for PPS with complete (HR 0.67, CI 0.49-0.90) and incomplete resection (HR 0.73, 95% CI 0.51-1.04) and confirmed methylation of the O6-methylguanine-DNA-methyltransferase (MGMT) gene promoter, lower age at diagnosis, absence of deep brain and multilocular localization, higher Karnofsky Performance Status (KPS) and recurrent therapies to be associated with longer PPS. In contrast, traditional eloquence and duration of progression-free survival had no effect on PPS. Subgroup analyses showed that all subgroups of confirmed predictors benefited from resection, except for patients in poor condition with a KPS &amp;lt;70. Conclusions Out data suggest a role for complete and incomplete recurrent resection in progressive GBM patients regardless of methylation of MGMT , age, or adjuvant therapy but not in patients with a poor clinical condition with a KPS &amp;lt;70.
pH-Dependent Partitioning of Ionizable Organic Chemicals between the Silicone Polymer Polydimethylsiloxane (PDMS) and Water
2022-02-16

The silicone polymer polydimethysiloxane (PDMS) is a popular passive sampler for <i>in situ</i> and <i>ex situ</i> sampling of hydrophobic organic chemicals. Despite its limited sorptive capacity for polar and ionizable organic chemicals (IOC), IOCs have been found in PDMS when extracting sediment and suspended particulate matter. The pH-dependent partitioning of 190 organics and IOCs covering a range of octanol-water partition constants log <i>K</i> <sub>ow</sub> from -0.3 to 7.7 was evaluated with a 10-day shaking method using mixtures composed of all chemicals at varying ratios of mass of PDMS to volume of water. This method reproduced the PDMS-water partition constant <i>K</i> <sub>PDMS/w</sub> of neutral chemicals from the literature and extended the dataset by 93 neutral chemicals. The existing quantitative structure-activity relationship between the log <i>K</i> <sub>ow</sub> and <i>K</i> <sub>PDMS/w</sub> could be extended with the measured <i>K</i> <sub>PDMS/w</sub> linearly to a log <i>K</i> <sub>ow</sub> of -0.3. Fully charged organics were not taken up into PDMS. Thirty-eight monoprotic organic acids and 42 bases showed negligible uptake of the charged species, and the pH dependence of the apparent <i>D</i> <sub>PDMS/w</sub>(pH) could be explained by the fraction of neutral species multiplied by the <i>K</i> <sub>PDMS/w</sub> of the neutral species of these IOCs. Seventeen multiprotic chemicals with up to three acidity constants p<i>K</i> <sub>a</sub> also showed a pH dependence of <i>D</i> <sub>PDMS/w</sub>(pH) with the tendency that the neutral and zwitterionic forms showed the highest <i>D</i> <sub>PDMS/w</sub>(pH). <i>D</i> <sub>PDMS/w</sub>(pH) of charged species of more hydrophobic multiprotic chemicals such as tetrabromobisphenol A and telmisartan was smaller but not negligible. Since these chemicals show high bioactivity, their contribution to mixture effects has to be considered when testing passive sampling extracts with <i>in vitro</i> bioassays. This work has further implications for understanding the role of microplastic as a vector for organic micropollutants.
Comparative Magnitude and Persistence of Humoral SARS-CoV-2 Vaccination Responses in the Adult Population in Germany
2022-02-16

Recent increases in SARS-CoV-2 infections have led to questions about duration and quality of vaccine-induced immune protection. While numerous studies have been published on immune responses triggered by vaccination, these often focus on studying the impact of one or two immunisation schemes within subpopulations such as immunocompromised individuals or healthcare workers. To provide information on the duration and quality of vaccine-induced immune responses against SARS-CoV-2, we analyzed antibody titres against various SARS-CoV-2 antigens and ACE2 binding inhibition against SARS-CoV-2 wild-type and variants of concern in samples from a large German population-based seroprevalence study (MuSPAD) who had received all currently available immunisation schemes. We found that homologous mRNA-based or heterologous prime-boost vaccination produced significantly higher antibody responses than vector-based homologous vaccination. Ad26.CoV2S.2 performance was particularly concerning with reduced titres and 91.7% of samples classified as non-responsive for ACE2 binding inhibition, suggesting that recipients require a booster mRNA vaccination. While mRNA vaccination induced a higher ratio of RBD- and S1-targeting antibodies, vector-based vaccines resulted in an increased proportion of S2-targeting antibodies. Given the role of RBD- and S1-specific antibodies in neutralizing SARS-CoV-2, their relative over-representation after mRNA vaccination may explain why these vaccines have increased efficacy compared to vector-based formulations. Previously infected individuals had a robust immune response once vaccinated, regardless of which vaccine they received, which could aid future dose allocation should shortages arise for certain manufacturers. Overall, both titres and ACE2 binding inhibition peaked approximately 28 days post-second vaccination and then decreased.
Immunological Predictors of Dimethyl Fumarate‐Induced Lymphopenia
2022-02-16

Treatment with dimethyl fumarate (DMF) leads to lymphopenia and infectious complications in a subset of patients with multiple sclerosis (MS). Here, we aimed to reveal immune markers of DMF‐associated lymphopenia. This prospective observational study longitudinally assessed 31 individuals with MS by single‐cell mass cytometry before and after 12 and 48 weeks of DMF therapy. Employing a neural network‐based representation learning approach, we identified a CCR4‐expressing T helper cell population negatively associated with relevant lymphopenia. CCR4‐expressing T helper cells represent a candidate prognostic biomarker for the development of relevant lymphopenia in patients undergoing DMF treatment. ANN NEUROL 2022;91:676–681
Spirituality, self-care, and social activity in the primary medical care of elderly patients—results of a cluster-randomized interventional trial (HoPES3)
2022-02-16

The main hypothesis concerning health-related self-efficacy was not confirmed. The results of the analysis ofsecondary parameters indicate that some subgroups of patients can benefit from the interventional approach.
Gradient Studies Reveal the True Drivers of Extreme Life in the Atacama Desert
2022-02-16

Abstract Studies of hyper‐arid sites contribute to our understanding on how life adapted to extreme conditions. They are often used to further deduce implications for extraterrestrial biology by the so‐called analogue site‐approach. The Atacama Desert, Chile, is one of the most prominent analogue sites despite its neighboring productive ecosystems due to its hyper‐aridity and geochemical features resembling Martian environments. We hypothesize that many drivers of extremophile life in analogue sites are only mistakenly attributed to aridity alone, thus obscuring a clear view of the far more complex process interactions originating in nearby earthly ecosystems. To test this, we investigated 54 soil profiles up to 60 cm of soil depth along of four transects in the Atacama Desert, either running parallel (S‐N) or perpendicular (W‐E) to the Andes. Our objective was to reveal the processes controlling the formation of soil organic carbon (SOC) as the most reliable proxy for microbial life in order to understand the boundary conditions of life in extreme habitats. Further, we aimed at identifying analogue sites as uncompromised as possible by external influences of for example, vegetated or marine ecosystems. We found a mixture of influences driving habitable conditions on gradients perpendicular to the Andes, for example, fog and precipitation scavenging caused by altitudinal variations and differing proximity to the Pacific Ocean, while transects parallel to the Andes were much less biased by external factors. Our results show that studies on life under extreme conditions should clarify the explanatory strength of the investigated factors by a gradient study approach.
Characteristics of serum neurofilament light chain as a biomarker in hereditary spastic paraplegia type 4
2022-02-16

Abstract Objective While the anticipated rise of disease‐modifying therapies calls for reliable trial outcome parameters, fluid biomarkers are lacking in spastic paraplegia type 4 (SPG4), the most prevalent form of hereditary spastic paraplegia. We therefore investigated serum neurofilament light chain (sNfL) as a potential therapy response, diagnostic, monitoring, and prognostic biomarker in SPG4. Methods: We assessed sNfL levels in 93 patients with SPG4 and 60 healthy controls. The longitudinal study of sNfL levels in SPG4 patients covered a baseline, 1‐year follow‐up and 2‐year follow‐up visit. Results Levels of sNfL were significantly increased in patients with genetically confirmed SPG4 compared to healthy controls matched in age and sex ( p = 0.013, r = 0.2). Our cross‐sectional analysis revealed a greater difference in sNfL levels between patients and controls in younger ages with decreasing fold change of patient sNfL elevation at older ages. Over our observational period of 2 years, sNfL levels remained stable in SPG4 patients. Disease severity and progression did not correlate with sNfL levels. Interpretation: Our longitudinal data indicate a stable turnover of sNfL in manifest SPG4; therefore, sNfL levels are not suitable to monitor disease progression in SPG4. However, sNfL may be valuable as a therapy response biomarker, since its turnover could be modified by interventions. As the course of sNfL levels appears to be most dynamic around the onset of SPG4, the ability to detect a therapy response appears to be especially promising in younger patients, matching the need to initiate treatment in early disease stages.
Assessing dissimilarity of employment history information from survey and administrative data using sequence analysis techniques
2022-02-16

Abstract Life course data is frequently gathered either using retrospective surveys or linking records with administrative data. Yet, each strategy has specific advantages and disadvantages. We study the consistency between both types of data sources and reasons for mismatch using the linked data set SHARE-RV, which combines retrospective life history data from the Survey of Health, Ageing and Retirement in Europe (SHARE) with respondents’ administrative data from German pension insurance records ( N = 1679). Utilizing sequence analysis techniques with Hamming distance, Optimal Matching and OMspell as matching algorithms, we examine mismatches between survey and administrative data covering detailed, 30-year employment histories, and analyze how inconsistencies are associated with life-course characteristics, demographic and socio-economic factors. Our results show that life-course complexity and spells of atypical employment are associated with more mismatches. Furthermore, gender differences are pronounced and appear to be sensitive to the applied matching algorithm.
Semantic object-scene inconsistencies affect eye movements, but not in the way predicted by contextualized meaning maps
2022-02-16

Semantic information is important in eye movement control. An important semantic influence on gaze guidance relates to object-scene relationships: objects that are semantically inconsistent with the scene attract more fixations than consistent objects. One interpretation of this effect is that fixations are driven toward inconsistent objects because they are semantically more informative. We tested this explanation using contextualized meaning maps, a method that is based on crowd-sourced ratings to quantify the spatial distribution of context-sensitive "meaning" in images. In Experiment 1, we compared gaze data and contextualized meaning maps for images, in which objects-scene consistency was manipulated. Observers fixated more on inconsistent versus consistent objects. However, contextualized meaning maps did not assign higher meaning to image regions that contained semantic inconsistencies. In Experiment 2, a large number of raters evaluated image-regions, which were deliberately selected for their content and expected meaningfulness. The results suggest that the same scene locations were experienced as slightly less meaningful when they contained inconsistent compared to consistent objects. In summary, we demonstrated that - in the context of our rating task - semantically inconsistent objects are experienced as less meaningful than their consistent counterparts and that contextualized meaning maps do not capture prototypical influences of image meaning on gaze guidance.
Overall survival (OS) in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) treated with enzalutamide (ENZA) + androgen deprivation therapy (ADT) by high or low disease volume and progression to mHSPC (M0 at diagnosis) or de novo mHSPC (M1 at diagnosis): Post hoc analysis of the phase 3 ARCHES trial.
2022-02-16

115 Background: In ARCHES (NCT02677896), ENZA + ADT improved radiographic progression-free survival, OS, and other key secondary endpoints vs placebo (PBO) + ADT for pts with mHSPC (also known as metastatic castration-sensitive prostate cancer). Final OS results confirmed a long-term survival benefit with ENZA + ADT (hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.53, 0.81; p&lt;0.0001). We present post hoc analyses of OS by disease volume and progression to M1 HSPC after initial diagnosis with localized disease (M0) or presentation of de novo mHSPC at initial diagnosis (M1). Methods: Pts with mHSPC (N=1150) were randomized 1:1 to ENZA (160 mg/day) + ADT (n=574) or PBO + ADT (n=576), stratified by disease volume and prior docetaxel use. After unblinding, 180 (31.3%) PBO + ADT-treated pts crossed over to open-label ENZA + ADT. High disease volume was defined per CHAARTED criteria. Medical profiles of pts assessed as MX/unknown metastasis at initial diagnosis (n=213) were further reviewed centrally and adjudicated as having either M0 or M1 disease. Median OS and HRs were estimated by Kaplan-Meier methods and Cox proportional hazards, respectively. Results: Median treatment duration was 40.2 months (mo) for ENZA + ADT and 13.8 mo for PBO + ADT. Inclusive of crossover, 401 (69.6%) PBO + ADT pts had subsequent life-prolonging therapy. OS benefits with ENZA + ADT were seen in all disease volume and M0/M1 populations at a similar magnitude to the overall population (Table). Median OS was not reached in most populations except PBO + ADT pts with high disease volume (45.9 mo; 95% CI 40.1, not estimable [NE]) or high disease volume and M1 disease (43.4 mo; 95% CI 36.4, 49.7) and ENZA + ADT pts with high disease volume and M0 disease (54.2 mo; 95% CI 54.2, NE). Conclusions: Our post hoc analysis demonstrates consistent long-term survival benefit with ENZA + ADT vs PBO + ADT across pts with mHSPC with high and low disease volumes and M0 or M1 disease at initial diagnosis, despite substantial treatment crossover and subsequent therapy use in PBO + ADT pts.[Table: see text]
Is it art? Effects of framing images as art versus non-art on gaze behavior and aesthetic judgments
2022-02-16

The perception and evaluation of art might be governed by both stimulus-driven aspects and expectations of the observer. By framing actual artwork and actual scientific depictions as being either artwork or scientific depictions, we were able to investigate the individual contributions of both factors on viewers’ gaze behavior and aesthetic judgments. With Experiment 1, we identified a set of images that were equally likely classified as being either artwork or scientific depiction by art laypersons. In Experiment 2, we measured art laypersons’ eye-movements as well as their aesthetic judgments regarding those images (half being actual artwork and half being actual scientific depictions). Importantly, we told one group of participants that all images were artwork, whereas we told another group of participants that all images were scientific depictions. Our results indicate that gaze behavior was influenced by the actual image type but not by framing. Actual artwork led to fewer and longer fixations, a shorter scanpath, a shorter distance of fixations to the screen center, and a lower similarity of viewing patterns across participants. Further, actual artwork was rated as being more complex but less meaningful than scientific depictions, with no differences regarding perceived structuredness and liking. Framing the images as artwork led to no changes in perceived meaningfulness, complexity, or structuredness but to lower ratings on liking. We conclude that while the dichotomy between art and non-art influenced art laypersons’ gaze behavior and aesthetic judgments, this influence was primarily driven by bottom-up factors rather than a specific cognitive art schema.